Adult Congenital Heart Disease

Eccentric Enlargement of the Aortic Sinuses in Pediatric and Adult Patients with Bicuspid Aortic Valves: A Cardiac MRI Study. Stefek HA, Lin KH, Rigsby CK, Michelena HI, Aouad P, Barker AJ, Robinson JD. Pediatr Cardiol. 2019 Dec 19. doi: 10.1007/s00246-019-02264-3. [Epub ahead of print] PMID: 31858201 Similar articles Select item 31858200   Take Home Points: In patients with a bicuspid aortic valve (BAV), root size and cusp fusion pattern is associated with disease outcomes This retrospective study characterised aortic sinus symmetry in adult and paediatric patients with a BAV and association to valvulopathy and aortopathy. Using CMR studies, 149 adults and 51 children with BAV were characterised and compared to 40 adults and 20 children with normal aortic valve morphology. In both adults and children with a BAV, the non-fused aortic sinus was larger than either fused sinus. Sinus eccentricity in BAV patients was significantly greater than in patients with a normal aortic valve. Degree of eccentricity varies with valve dysfunction and BAV phenotype but, does not relate to degree of aortic root dilation. In adults, degree of eccentricity does not correlate with ascending aortic dilation. Commentary from Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch: The BAV is the commonest congenital cardiac lesion and seen in approximately 0.5%-2% of the population. Congenital cardiologists will frequently encounter the patients with the long-term consequences of BAV – namely, aortic stenosis, aortic regurgitation, a combination of both with and without an aortopathy. It is challenging to predict disease progression in the individual patient. Valves with fusion of right-left coronary cusps are more likely to develop AI whilst valves with fusion of right and non-coronary cusps are more likely to develop stenosis. Furthermore, aortopathy is influenced by different BAV phenotypes, probably due to the eccentricity of the outflow jet through the BAV.   A flowchart showing the process for patient selection is shown in Figure 1. Of the adult patients with a BAV (n=149) the mean age was 48 years old. Of the paediatric patients with BAV (n=51), the mean age was 15 years old. The demographics of patients with BAV phenotype and aortic valve disease and aortopathy is shown in Table 1.     Figure 1. Flowchart of inclusion and exclusion criteria used in formation of paediatric and adult study cohorts (CMR cardiac MRI, AAo ascending aorta, RL BAV with right-left cusp fusion, RN BAV with right-non coronary cusp fusion)   Table 1. Patient demographics in BAV and normal aortic valve cohorts     Conclusions This study showed that patients with BAV exhibit significant sinus asymmetry characterised by preferential non-fused sinus dominance. Eccentricity is seen in both adults and children – it isn’t associated with age suggesting possible genetic pre-disposition. In this small study, there was no statistically significant difference in degree of eccentricity of the aortic root in either adults or children with RL or RN cusp fusion. Larger observational studies are required.   

More than the heart: Hepatic, renal, and cardiac dysfunction in adult Fontan patients. Byrne RD, Weingarten AJ, Clark DE, Huang S, Perri RE, Scanga AE, Menachem JN, Markham LW, Frischhertz BP. Congenit Heart Dis. 2019 Jul 7. doi: 10.1111/chd.12820. [Epub ahead of print] PMID: 31282062 Similar articles Select item 31282223   Take Home Points: MELD and MELD-XI are scoring systems used to assess the severity of chronic liver disease. Systolic ventricular dysfunction and decreased oxygen saturation were associated with hepatic and renal dysfunction which were shown by an increase in MELD and MELD-XI scores and creatinine level.   Commentary from Dr. M.C. Leong (Kuala Lumpur, Indonesia), section editor of ACHD Journal Watch: The Model for End-Stage Liver Disease (MELD) is a scoring system used to assess the severity of chronic liver disease by using the patient’s serum bilirubin, serum creatinine and the international normalized ratio (INR). It is used originally to predict survival of patients and to decide for liver transplant in patients post transjugular intrahepatic porto-systemic shunt (TIPS) procedure.   MELD = (3.78 × ln[total serum bilirubin (mg/dL)]) + (11.2 × ln[INR]) + (9.57 × ln[serum creatinine (mg/dL)]) + 6.43.   A modified scoring systemic named MELD-XI, which omits INR from its equation, has been used to correlate the impact of failing Fontan and hepatic fibrosis. The reason behind omitting INR from the equation was due to the high prevalence of Warfarin use in patients with Fontan.   MELD‐XI = (11.76 × ln[serum creatinine (mg/dL)]) + (5.11 × ln[total serum bilirubin(mg/dL)]) + 9.44.   This study aimed to investigate the association between MELD and MELD-XI; and Fontan circuit congestion and dysfunction in 98 patients post-Fontan (age 15 years or older). Of the hemodynamic variable analyzed, decreased oxygen saturation and moderate to severe reduction in ejection fraction, measured via echocardiography, were associated with increased MELD and MELD-XI scores as well as increased creatinine levels. Age at Fontan, systemic ventricular morphology, degree of atrio-ventricular valve regurgitation and Fontan pressures were not associated with elevated MELD, MELD-XI scores and creatinine levels.         MELD and MELD-XI scores still lack evidence to link its association with failing Fontan. Also, they may be useful as surrogate biochemical markers to monitor hepatic fibrosis patients with Fontan circulation but not as a tool to predict the risk of Fontan associated liver disease. Nevertheless, it may present as a good biochemical marker to complement the already available monitoring tools.   

Ventilatory and sensory responses to incremental exercise in adults with a Fontan circulation. Guenette JA, Ramsook AH, Dhillon SS, Puyat JH, Riahi M, Opotowsky AR, Grewal J. Am J Physiol Heart Circ Physiol. 2019 Feb 1;316(2):H335-H344. doi: 10.1152/ajpheart.00322.2018. Epub 2018 Nov 2. PMID: 30388023 Similar articles   Take Home Points: Compared to controls, patients with Fontan circulation have: restrictive ventilatory impairment, higher ventilatory requirement for the same amount of work rate, and higher sensory response to exercise (breathing and legs discomfort) at a given work rate.   Commentary from Dr. M.C. Leong (Kuala Lumpur), section editor of ACHD Journal Watch: The reduced exercise capacity in patients with Fontan circulation is largely thought to be driven by the inability of the heart to increase preload to match the increase of cardiac output. Though not systemically studied before, pulmonary function abnormalities during exercise may also be a contributing factor to reduced exercise capacity. This study aimed to describe the ventilatory and sensory response during exercise in adults with Fontan circulation.   This is a case control study involving 17 patients with Fontan circulation and 17 matched controls. The authors found that patients with Fontan had lower values for most pulmonary function measurements (Table 3). They had a lower total lung capacity but at the same time, a normal FEV1/FVC ratio, suggesting an inherent restrictive ventilatory defect. They also had significantly higher breathing frequency, end-inspiratory lung volume, ventilator inefficiency (high VE/VCO2) and dyspnea. In terms of sensory response, patients with Fontan achieved a breathing discomfort and legs discomfort scores similar to controls at a much lower work rate (Figure 5). There was no difference in the qualitative descriptors of dyspnea and the dyspnea intensity rating. The authors noted that patients in the Fontan group had other confounding factors such as poorer ventricular function, atrio-ventricular valve regurgitation and beta-blocker use which may affect exercise capacity and the sensory response of these patients.         

Differences in Cardiovascular Manifestation of Marfan Syndrome Between Children and Adults. Wozniak-Mielczarek L, Sabiniewicz R, Drezek-Nojowicz M, Nowak R, Gilis-Malinowska N, Mielczarek M, Łabuc A, Waldoch A, Wierzba J. Pediatr Cardiol. 2019 Feb;40(2):393-403. doi: 10.1007/s00246-018-2025-2. Epub 2018 Nov 11. PMID: 30417312 Similar articles Select item 30415381   Take Home Points: Aortic root and ascending aorta dilatation, mitral valve prolapse and aortic regurgitation are equally prevalent in children and adults, while aortic arch, descending aorta and pulmonary truck dilatation are more common in adults. Aortic root dilatation is the primary cardiovascular manifestation of Marfan syndrome (81%), equally prevalent in adults and children with no predilection for male or female sex. Dilatation of the sinotubular junction (33%) and distal ascending aorta (27%) occurs in similar frequency amongst adults and children, and always in association with aortic root dilatation. Aortic arch (9 %) and descending thoracic or abdominal aorta (11%) dilatation is more common in adult patients than children. Aortic dissection was retrospectively noted in 8 patients (8%) at a mean age of 26 +/- 7 years; 3 of 4 females (75 %) were affected during the third trimester of pregnancy. Aortic valve regurgitation present in 26 patients (31%) but only mild in the majority (92%). Mitral valve prolapse is common in adults and children (53 and 57%, respectively). Pulmonary trunk dilatation is more frequent in adults as compared to children (37 vs. 16%, P=0.025).   Commentary from Dr. Timothy Roberts (Melbourne), section editor of ACHD Journal Watch: This observational study aimed to assess differences in the frequency of cardiovascular manifestations of Marfan syndrome in a series of 236 patients referred for assessment of suspected Marfan syndrome. Referral indications included body stature (27 %), family history of Marfan syndrome (24 %), joint hypermobility (14 %), chest deformity (7 %), scoliosis (6 %), aortic dilatation or dissection (5 %) and lens dislocation (5 %). Marfan syndrome was diagnosed in 101 patients (43 %: 44/144 children, 57/92 adults) according to the modified Ghent criteria. The mean age at diagnosis of Marfan syndrome was 24 +/- 15 years (2 months – 65 years) with 46 % female gender. A family history of Marfan syndrome was present in 68 %. Genetic testing was not performed to confirm a clinical diagnosis of Marfan syndrome. Cardiovascular testing involved electrocardiography, 24-hour ambulatory monitoring and transthoracic echocardiography.   Aortic root dilatation was present in 81 % of Marfan subjects, affecting adults (49/57, 86 %) and children (33/44, 75 %) to a similar extent. A modest correlation was demonstrated between aortic root diameter and patient age (R=0.335, p=0.008). Subjects were further sub-grouped into four age categories (2 months – 9 years, 10 – 17 years, 18 – 29 years, and 30 – 65 years) with the highest z-score observed in adults (4.69 in 18 – 29 year group, 4.25 in the 30 – 65 year group; P=0.429). There was no difference in degree of aortic root dilatation according to sex.   Aortic arch dilatation occurred in 9 patients (9 %), more frequently in adults than children (P=0.04). Similarly, adults had a greater prevalence of descending thoracic or abdominal aorta dilatation (18 vs. 2 %, p=0.015).   Aortic dissection (retrospectively) occurred in 8 subjects: 6 adults (11 %) and 2 children (5 %). Type A dissection contributed to 5 of these events. Of note, 3 of the four females with dissection were affected during the third trimester of pregnancy.   Aortic regurgitation was diagnosed in 26 patients (31 %), being only mild in the majority and moderate in two adults (8 %). Prevalence was not different in adults and children. Four subjects had bicuspid aortic valve morphology.   Mitral regurgitation of any aetiology and severity was more common in adults than children (77 vs. 45 %, P=0.002), however the prevalence of mitral valve prolapse was similar (54 %) and severe mitral regurgitation was demonstrated in < 10 % of subjects overall.   Ambulatory 24-hour monitoring identified frequent (> 1000/day) ventricular (9 %) and supraventricular extrasystoles (5 %) without a statistically significant difference between adult and child subjects.     The data presented in the current study is informative while limited by the lack of longitudinal data. Nonetheless, similar to other studies it identifies high rates of aortic root dilatation and mitral valve prolapse, both of which are equally prevalent amongst children and adults. A further important point to highlight is the risk of aortic dissection during pregnancy. Although the affected women in this study were not formerly diagnosed with Marfan syndrome at the time of dissection, we must never forget the importance of pre-pregnancy counselling and to have a low threshold for aortic root surgery in our female Marfan syndrome patients of child-bearing age.   

Lifelong burden of small unrepaired atrial septal defect: Results from the Danish National Patient Registry. Udholm S, Nyboe C, Karunanithi Z, Christensen AI, Redington A, Nielsen-Kudsk JE, Hjortdal VE. Int J Cardiol. 2019 May 15;283:101-106. doi: 10.1016/j.ijcard.2019.02.024. Epub 2019 Feb 16. PMID: 30826194 Similar articles   Take Home Points An analysis of survival and morbidity of all patients with a small unrepaired ASD listed in the Danish National Patient Registry (DNPR) between 1953 and 2011 compared to the background population. 723 patients were defined as having a small unrepaired ASD in the DNPR. Since the time of diagnosis 182 patients (25%) had died with a mean lifespan of 63 years. Mean age at diagnosis was late in these patients – 53 years. The commonest cause of death was heart failure. Compared to the general population, patients with an ‘insignificant’ unrepaired ASD had a higher burden of chronic disease (27% vs 38%, p=0.005) – particularly lung disease (1% vs 4%). In a select number of patients aged 18-65 years, listed as having a small unrepaired ASD whom underwent TTE (n=153), the ASD had spontaneously closed in 80% (n=123). 6MWT was significantly lower (632+/- 90m) in patients previous diagnosed with an ASD vs calculated reference values (715 +/- 94m, p=0.00001). Further investigation and data collection is required to help explain why morbidity and mortality should be worse in patients with a seemingly ‘low risk’ congenital cardiac anomaly, even when the ASD closes spontaneously. Commentary from Dr. Damien Cullington (Leeds UK), section editor of ACHD Journal Watch: The Danish National Patient Registry (DNPR) is a remarkable epidemiological feat which has collated complete data on all residents living in Denmark since 1977. It contains information on all inpatient and outpatient hospital contacts in Denmark and diagnoses are made according to ICD definitions. Only patients with ASDs deemed to be ‘insignificant’ i.e. unrepaired, small, and with a Qp:Qs <1.5 were included in the analysis.   Between 2015 and 2018, patients remaining alive and aged 18-65 yrs. with an unrepaired ASD (n=361) were invited to undergo further testing – a questionnaire, TTE, spirometry and 6MWT – only 156 patients were included in this more extensive assessment (Fig 1)   Patients with an ASD 2277 adult patients were listed in the DNPR as having an ASD. Of these, just over two thirds of patients (n=1554) had surgical or device ASD closure. The remainder (n=723) had an unrepaired ASD. It is unclear how patients with seemingly small ASDs were diagnosed – often such patients are completely asymptomatic with few clinical signs on examination. It is inevitable that there are many more patients in the general population with small, ‘innocuous’ ASDs which are still undiscovered.   A quarter of patients with an unrepaired ASD (n=182) died at a mean age of death of 63 years (range 0.2-99.1 years). Of note, the mean age at diagnosis of those patients who died was relatively advanced at 53 +/-27 years old. Nearly half of deaths (n=47) were of cardiac aetiology. Figure 1. Flowchart of patient inclusion     Echo data (n=153) On TTE assessment, most ASDs had spontaneously closed and there were only 30 patients who had small, open ASDs. (Fig 2). Patients who still had a small ASD compared to those who had closed spontaneously, had larger right heart dimensions. No differences were seen in ventricular function, estimated filling pressures or estimated pulmonary pressures. The mean age at diagnosis of this patient cohort was 9 years old.   Conclusions It is not clear from this analysis why patients with seemingly small, innocuous ASDs, even in those which have spontaneously closed have worse survival, more chronic disease, higher levels of anxiety and worse functional capacity. Continued observation and collection of epidemiological data is required. It is not clear if earlier closure of these small ASDs, often viewed as seemingly benign, can avert these adverse outcomes. Patients with even small ASDs should be followed up longer term to check for any clinical deterioration.   Figure 2. Echocardiographic data from selected patients listed in the DNPR as having an unrepaired ASD (n=153) who subsequently had echo. The ASD had spontaneously closed (n=123) vs remainder open (n=30).     

Sudden death in transposition of the great arteries with atrial switch surgery: Autopsy evidence of acute myocardial ischemia despite normal coronary arteries. Chaix MA, Chergui M, Leduc C, Khairy P. Int J Cardiol. 2019 Feb 14. pii: S0167-5273(18)36331-9. doi: 10.1016/j.ijcard.2019.02.026. [Epub ahead of print] PMID: 30808604 Similar articles Select item 30765829   Take Home Points: Sudden cardiac death remains a leading cause for mortality in patients with transposition of the great arteries and an atrial switch. This study provides evidence for a proposed mechanism: myocardial oxygen mismatch of the systemic RV when atrial rates are high, resulting in ischemia-driven ventricular arrhythmias and sudden cardiac death.   Commentary by Dr. Blanche Cupido (Cape Town), section editor of ACHD Journal Watch: In patients with transposition of the great arteries and an atrial switch repair, sudden cardiac death is the main cause of mortality. The decision making for a primary prevention ICD remains difficult with little evidence to substantiate it. A proposed mechanism for sudden cardiac death in this group is thought to be myocardial oxygen supply mismatch of the systemic RV during high heart rates resulting in ischemia- related ventricular arrhythmias and death. This study provides histopathologic evidence in support of this theory.   This is a retrospective cohort study in Montreal, Canada of adults with transposition of the great arteries with an atrial switch procedure. Patients attending their clinic from 1989 onward were enrolled. Those patients with arterial switches or double outlet RV were excluded.   A total of 140 patients were analyzed. The average age was 37.6 years and 37.1% were female. A total of 8 patients (6% - 3 female, 5 male) had a cardiac arrest (of assumed arrhythmic cause) – three of these were successfully resuscitated. None had a prior history of coronary artery disease, ventricular arrhythmia or syncope.   Four patients had atrial arrhythmias, one had non-sustained VT on a Holter (asymptomatic) and two had pacemakers. Two thirds had at least moderate systemic RV dysfunction. Most patients (7 of 8) had NYHA I or II. For 5 patients, the circumstances around the time of arrest were documented: 3 events occurred on exertion, 1 at rest and 1 after methamphetamine use.   Of the 5 patients who died, 2 autopsies were performed. One patient died suddenly 7 days post -op (tricuspid valve replacement) and the other while walking to work (VT documented). Both had extensive acute necrosis of the hypertrophied systemic RV with normal coronary arteries and chronic subendocardial lesions.   These histopathological findings support the following theory: At rapid heart rates, stroke volume is impaired due to poor atrial contraction. This reduction in stroke volume together with the increased oxygen demand, decreased perfusion pressure and inefficient coronary circulation (systemic RV usually only has single coronary supply), induces ischemic ventricular arrhythmias.   

Multimodality Screening of Hepatic Nodules in Patients With Congenital Heart Disease After Fontan Procedure: Role of Ultrasound, ARFI Elastography, CT, and MRI. Horvat N, Rocha MS, Chagas AL, Oliveira BC, Pacheco MP, Binotto MA, Ikari NM, Paranaguá-Vezozzo DC, Leao-Filho HM, Vicentini JRT, Moreira da Silva Filho MR, Jatene MB, Carrilho FJ, Cerri GG. AJR Am J Roentgenol. 2018 Dec;211(6):1212-1220. doi: 10.2214/AJR.18.19762. Epub 2018 Sep 24. PMID: 30247977 Similar articles Select item 30343246   Take Home Points: In a series of asymptomatic Fontan patients, hepatic nodules were found on screening in 6.1%, 31.8%, and 39.6% respectively on US, CT and MRI. There was an almost perfect agreement between CT and MRI. No correlation was found between the presence of hepatic nodules and clinical or laboratory data. Liver stiffness on ARFI was a significant predictor of hepatic nodules (AUC 0.767, p=0.0002). For ARFI, a cut-off of 2m/s has a sensitivity of 78.9% and a specificity of 67.9%.   Commentary by Dr. Blanche Cupido (Cape Town), section editor of ACHD Journal Watch: Fontan liver disease is thought to be multifactorial and may result in liver fibrosis, cirrhosis with or without portal hypertension, hepatic nodules and even hepatocellular carcinoma. There is no consensus regarding the screening for liver pathology, especially with regards to imaging after a Fontan procedure.   This is a single-center cross-sectional study of patients with a Fontan circulation. They aimed to assess the presence of hepatic nodules by US, CT ad MRI, to measure liver stiffness and to identify factors predictive of nodules. Patients were recruited between August 2014 to June 2016. Pregnant patients and those who could not undergo CT or MRI were excluded.   Forty-nine patients were included – they underwent a hepatology clinical consult, upper abdominal US, liver acoustic radiation force impulse (ARFI) elastography, upper abdomen triple-phase CT and MRI on the same day. Cardiology data was reviewed retrospectively.   Of the 49 patients, 57.1% were female. The mean age was 26.2 years. Patients were mostly asymptomatic (2 had ascites). All patients had normal levels of alpha-fetoprotein.   Hepatic nodules were found in 3 of 49 patients on US (6.1%), in 14 of 44 patients (31.8%) on CT and in 19 of 48 patients (39.6%) on MRI. All nodules were <3cm in size. None of the nodules displayed features of malignancy.   There were no clinical differences between the patients with hepatic nodules and those without (i.e. no difference in terms of time since Fontan procedure, no difference with regards to the type of Fontan, the presence of a fenestration).   With regards to liver stiffness, mean velocities at ARFI were significantly higher in those with hepatic nodules compared to those without (2.64 m/s vs 1.94m/s, p=0.002). It was significantly lower in those who had heart transplants (0.93 vs 2.28m/s, p=0.002).     Shear-wave propagation velocity at ARFI elastography was a significant predictor of the presence of hepatic nodules – AUC 0.767 (p=0.002). By using a cut-off of 2m/s, ARFI had a sensitivity of 78.9% and a specificity of 67.9%.     

Utility of Follow-Up Annual Echocardiograms in Patients With Complete Transposition of the Great Arteries After Arterial Switch Operations. Shivaram P, Padiyath A, Bai S, Gossett JM, Thomas Collins R. Am J Cardiol. 2018 Dec 1;122(11):1972-1976. doi: 10.1016/j.amjcard.2018.08.044. Epub 2018 Sep 8. PMID: 30318419 Similar articles   Take Home Points This retrospective analysis questioned how often in asymptomatic patients (mostly paediatric) with no change in physical exam, that transthoracic echocardiography (TTE) altered clinical practice. Over a 32 year period (1983-2015), a total of 1792 TTEs of 149 patients were reviewed. 93% of TTEs examined were in patients <15 years old. The median number of echocardiograms per patient was 12 (range 1-34). Only 20 echocardiograms (1.1%) led to an ‘actionable change’ in clinical management i.e. medication change, interventional catheter or surgical procedure. The most common intervention was for a cardiac catheter (13 out of 20, 65%) and most actionable changes occurred in a 10 year interval after the arterial switch procedure. This retrospective analysis conjects that patients with an arterial switch may be subject to overinvestigation (i.e. echocardiography). There is the potential to rationalise and increase the scan interval between TTEs in patients who have undergone a simple arterial switch procedure, particularly in the paediatric age range. The number of adult patients in this analysis was small so assessing the utility of TTE surveillance in adult patients who have undergone ASO in childhood requires further investigation.   Commentary from Dr. Damien Cullington (Leeds UK), section editor of ACHD Journal Watch: Patients with a history of transposition of the great arteries (TGA) who have undergone the arterial switch operation (ASO) comprise a growing body of patients attending for regular ACHD follow up. For about the last 30 years, in most congenital cardiac surgical centres, the ASO has replaced the atrial switch for treatment of TGA- apart from perhaps the most challenging of cases. For the management and planned follow up for many congenital cardiac conditions, generic guidance has been arbitrarily defined and recently updated in the 2018 AHA/ACC guidelines for the management of adults with congenital cardiac disease. For adult patients who are clinically well, it is recommended that TTE interval assessment can be individualised and repeated every 12-24 months.   Shivaram et al. have performed a retrospective analysis of TTEs, mostly in paediatric patients which sought to question what the utility of an annual echo is in patients who have had an ASO – does this result in an ‘actionable change’ (AC)? The clinical characteristics of the population are shown in Table 1. An AC found on TTE was defined by the authors as one which was not secondary to change in symptoms or physical examination but resulted in at least one of four interventions – medication change; hospital admission; cardiac catheter +/- intervention; or surgical intervention.   Results Over a period of 32 years, only patients with d-TGA who underwent ASO were enrolled. Out of 193 patients identified, 44 were excluded as their study data was inadequate, leaving 149 patients for analysis. An impressive number of TTEs were examined but the majority were performed within a year after surgery (n=931, 53%). Only 51 TTEs (3% of the total) were performed in patients > 20 years old (Table 2).   Table 2 The results show that in a paediatric age group, most patients following ASO are clinically stable from a TTE perspective. Most ACs (90%) occurred in patients <15 years (Table 3) with a greater tendency for ACs to occur in more complex forms of ASO Table 4.   Table 3   Table 4   Utility of TTE surveillance in adult patients undergoing ASO. The number of patients in the analysis who had reached adulthood was only small – only 33 patients were >15 years old (22% of the cohort) with rapidly diminishing numbers thereafter (Figure 1). This is important to highlight since this study cannot confidently assess the long-term utility of TTE surveillance in comparison to the larger number of patients in the paediatric age range group.   Figure 1 Conclusions In this analysis there appears to be very low rates of complications requiring re-intervention after childhood ASO. Patients with more complex ASO have a tendency for more complications. It is suggested that for those patients with simple TGA as their original anatomy, scans intervals could potentially be more widely spaced.   Although the authors assert that follow up TTEs ‘are rarely of any clinical utility’, we can’t forget that for some patients and their families, investigations like a TTE, can help to give clinical assurances and some families will view this as a standard component of a thorough clinical evaluation irrespective of the low likelihood of complications occurring. Care should be individualised.   This analysis focusses primarily on a paediatric age group rather than an adult one so extrapolating the available evidence to make recommendations on the utility of TTE surveillance in adults with ASO should be explored further.   

Determinants of Left Ventricular Dysfunction and Remodeling in Patients With Corrected Tetralogy of Fallot. Andrade AC, Jerosch-Herold M, Wegner P, Gabbert DD, Voges I, Pham M, Shah R, Hedderich J, Kramer HH, Rickers C. J Am Heart Assoc. 2019 Sep 3;8(17):e009618. doi: 10.1161/JAHA.118.009618. Epub 2019 Aug 31. PMID: 31474177 Free PMC Article Similar articles Select item 31450994   Take-Home Points: Both impaired systolic and diastolic dysfunction of the LV, adverse remodeling with ECM expansion, myocardial atrophy and a reduced   mass/volume ratio are seen in asymptomatic (NYHA I) with rTOF. These markers of LV systolic dysfunction are associated with  reduced peak oxygen consumption during CPET and thus a predictor of poorer outcome in rTOF. Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch:  In patients with repaired Tetralogy of Fallot (rTOF), pulmonary regurgitation and RV dilatation and function is usually the focus at clinical follow-up. LV dysfunction too has been found to be a predictor of death and sustained ventricular tachycardia in rTOF.  This is a cross-sectional study aiming to assess the prevalence of LV dysfunction in asymptomatic (NYHA I) patients with rTOF and to identify the associations between right heart markers of pathologic remodeling and LV remodeling. Furthermore, in a subset of patients, cardiopulmonary exercise testing was done and the effect of LV remodeling and dysfunction on age-and sex-adjusted peak exercise parameters were assessed. This was a prospective cross-sectional study at a tertiary center in Sao Paulo, Brazil. One hundred and three consecutive patients with rTOF and NYHA I were enrolled between January 2012 and August 2016. Baseline characteristics are displayed in Table1 below.   Of the 103 patients enrolled with rTOF, 43 were female. Patients were studied at 15.1±8.7 years after surgical repair. Twenty patients had initial shunt implantations, 49% (n=51) had a transannular patch repair. Furthermore, 24% (n=25) had re-operations for mainly PR.   There were no differences in age, weight, height, BSA and blood pressure between patients and healthy controls. Referring to table 2 above, RV mass index, indexed RV end-systolic and end-diastolic volumes as well as RV mass/volume ratios were significantly higher in rTOF patients compared to healthy controls. In patients with rTOF, LV EF, LV mass index, LV mass/volume ratio and LV/RV mass ratio were markedly reduced compared to healthy controls.  LVEDVi however did not differ between subjects and controls but correlated with RVEDVi (r=0.36, p<0;.001). LA volumes and function were also decreased compared to controls. Table 3 shows, for each LV parameter, the proportion of patients with rTOF with values falling out of the corresponding age related 95% CI’s. In patients with rTOF, LVEF correlated with RVEF (p=0.41, p<0.001; 95%CI 0.26-0.54) and RV mass/volume ratio (p=0.33, P<0.001). In total, 23% had moderate LVEF impairment (EF 35%-45%) and 41% had mild dysfunction (EF 45-55%), 36% had normal LVEF. Figure 2 A above shows that LV systolic dysfunction is associated with remodeling of the RV, as per RV mass-to-volume-ratio. This remained significant in a multivariate module. LV systolic dysfunction is also associated with RVESVi. Figure 4 shows that 28% of all patients with rTOF had LV mass / volume ratio below the age-specific 5th percentile level in healthy controls.          Figure 4A Late Gadolinium enhancement (LGE) was performed in 65 of the cohort. In 95% of these patients, the site was the ventricular septum, 46% showed LGE in the RVOT and 13.8% in other areas of the heart but not the free wall. Cardiopulmonary testing results (CPET) were available in 70 patients with rTOF. VO2max was less than the 3rd centile in 29% of patients.  

Assessment and Implications of Right Ventricular Afterload in Tetralogy of Fallot. Egbe AC, Taggart NW, Reddy YNV, Sufian M, Banala K, Vojjini R, Najam M, Osman K, Obokata M, Borlaug BA. Am J Cardiol. 2019 Sep 9. pii: S0002-9149(19)31003-3. doi: 10.1016/j.amjcard.2019.08.035. [Epub ahead of print] PMID: 31586531 Similar articles Select item 31501090   Take-Home Points: High RV pressure after repair of tetralogy of Fallot (TOF) adversely affects clinical outcomes. Invasively measured right ventricular systolic pressure (RVSP) and TOF with pulmonary atresia are independent risk factor for death and/ or heart transplant. Doppler-derived RVSP has good correlation between invasively measured RVSP and is independently predictive of death and / or heart transplant.  Commentary by Dr. M.C. Leong (Kuala Lumpur, Malaysia), section editor of ACHD Journal Watch:  In the attempt to preserve the pulmonary valve during surgery, surgeons usually leave patients with residual right ventricular outflow tract (RVOT) obstruction either at the pulmonary annular or perivalvular level after the repair of tetralogy of Fallot (TOF). Often, this is seen as benign as the residual RVOT is usually not high and in fact, may even promote development of restrictive right ventricular physiology which may mitigate progressive right ventricular dilatation. However, if the right ventricular systolic pressure is left high for a chronic period of time, its long term effect onto the right ventricle is unknown.  This paper studied the effect of significant elevated right ventricular afterload, whether it independently affects the clinical outcomes of patients with TOF. This is a retrospective study, looking at 266 patients who underwent cardiac catheterization during follow up. Of these, 175 (66%) patients had significant RVOT obstruction, which was defined as a peak-to-peak gradient of greater than 36mmHg, on direct measurement. Within this cohort, 212 patients had echocardiography within 48 hours of the cardiac catheterization. These patients were followed up for 12.9 ± 7.3 years from the time of invasive study. During this period 35 (13%) patients died at a mean age of 49 ± 14 years. Of these, 27 patients had significant RVOT obstruction while 8 patients did not. There was no significant difference in mortality between patients with versus without significant RVOT obstruction. Invasively measured RVSP and TOF-pulmonary atresia were independent risk factors for death and/or heart transplant. There was a strong correlation between the invasively measured right ventricular systolic pressure (RVSP) and that of echocardiographic Doppler-derived, with a mean difference of +6mmHg suggesting that follow up using echocardiography is accurate yet noninvasive. Doppler-derived RSVP was independently predictive of death and / or transplant. It is interesting to note that TOF-pulmonary atresia itself was a risk factor for death and heart failure. With increasing attempts of unifocalization of the aorto-pulmonary collaterals and incorporating them into the pulmonary arterial tree as well as total repair when the pulmonary arterial size is less than desired, many patients are left with high RVSP and this paper underscores the effects of having a high RVSP in this group of patients. A caveat to this paper is the fact that patients who undergo invasive investigation are those with poorer hemodynamics and inherently are at a higher risk of death and heart failure. Hence many of these patients are higher risk patients compared to the general TOF population.  

External Validation of 3 Risk Scores in Adults with Congenital Heart Disease. Ramchandani BK, Polo L, Sánchez R, Rey J, González Á, Díez J, Aroca Á. Korean Circ J. 2019 Sep;49(9):856-863. doi: 10.4070/kcj.2019.0015. Epub 2019 May 7. PMID: 31165593 Free PMC Article Similar articles Select item 31582699   Take-Home Point: There was no significant difference in discrimination between the 3 mortality predictors.  However, calibration showed RACHS 1 underpredicted mortality, Aristotle overpredicted mortality and Euro 1 was mis-calibrated.    Commentary from Dr. Helen Parry (Leeds UK), section editor of ACHD Journal Watch: Aim:   To compare RACHS-1, Aristotle and EURO-1 risk scores in predicting in hospital mortality for patients undergoing surgery for congenital heart disease in adulthood Methods:  The study was performed retrospectively in a single centre in Spain, looking at operations performed over a 26 year period.   The primary end-point was 30 day mortality, looked at each of the above scores and looked at correlation with mortality.  This was assessed by discrimination (ability to predict death, using the area under the curve) and calibration (accuracy of the prediction). Results:   Six hundred and eight procedures were performed on adult patients with congenital heart disease.  There was no significant difference in discrimination between the 3 mortality predictors.  However, calibration showed RACHS 1 under predicted mortality, Aristotle over predicted mortality and Euro 1 was mis-calibrated. Discussion:  The authors suggest that RACHS 1 and Aristotle are superior to Euro 1 in congenital heart disease patients.  RACHS 1 and Aristotle take greater account of the complexity of patients with congenital heart disease e.g. those with genetic disorders.  However, RACHS 1 and Aristotle also look at birth weight and prematurity, which are less relevant in adults relative to paediatrics. Strengths of the study: Large sample size Representative case mix including high percentage of re-do sternotomies Weaknesses of the study: Single centre and retrospective It would also have been useful to have more details on the mortalities e.g. why did a 32 year old male attending for a PVR die of a myocardial infarction?  

The Prognostic Value of Myocardial Deformation in Adult Patients With Corrected Tetralogy of Fallot. van Grootel RWJ, van den Bosch AE, Baggen VJM, Menting ME, Baart SJ, Cuypers JAAE, Witsenburg M, Roos-Hesselink JW. J Am Soc Echocardiogr. 2019 Jul;32(7):866-875.e2. doi: 10.1016/j.echo.2019.03.014. Epub 2019 May 4. Similar articles   Take Home Points: There is a clear role for strain analysis in adult patients with repaired ToF. Reduced myocardial deformation parameters, including RV longitudinal strain and LV apical rotation, are associated with worse outcomes in clinically stable patients with repaired ToF, independent of currently known markers. To enhance risk stratification, myocardial deformation imaging should be considered as an additional tool in routine clinical follow-up, but not to replace currently used strategies. Commentary by Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch: van Grootel et al studied the myocardial deformation by echocardiography speckle-tracking analysis of both ventricles in asymptomatic adults with repaired ToF and its relationship with adverse outcome. This is a prospective observational study that included all clinically stable patients with repaired ToF, visiting the outpatient clinic between 2011 and 2013. Exclusion criteria were age < 18 years, pregnancy, and inability to understand and sign informed consent forms; patients were also excluded in case of poor echocardiographic image quality. Myocardial strain analysis included: 1- The left ventricle was assessed according to the 17-segment model as stated in the guidelines for echocardiographic chamber quantification. The rotation at the basal and apical levels of the left ventricle was measured by applying speckle-tracking after identifying the endo- and epicardial borders in the basal and apical short-axis views. 2- RV systolic function was assessed by measuring RV longitudinal strain (LS) of the free wall. The software describes clockwise rotation as a positive value and counterclockwise rotation as a negative value. The peak apical rotation and basal rotation during systole was assessed. Twist was calculated and defined as the maximum value of the simultaneous difference between apical rotation and basal rotation (apical minus basal rotation) during systole. Strain measurements were blinded. Definition and assessment of events:The primary endpoint was a composite of death or heart failure. Heart failure was defined as requiring changes in HF medication or hospital admission. The secondary endpoint was a supraventricular or ventricular arrhythmia (symptomatic and recorded or treated), hospitalization for cardiac reasons, or reintervention (both surgical and percutaneous). End points were manually tracked on a yearly basis. Results: In total, 179 patients were eligible in the original cohort. Of these, 28 (16%) were excluded because of poor echocardiographic image quality. Of the 151 patients included, the median age was 34.6 years [IQR, 27.9–44.9 years] and  65.1% were men. The control group of 88 subjects had a median age of 31.2 years (IQR, 25.3–41.9 years), and 48 (54.5%) were men. All patients had significantly lower myocardial deformation compared to controls (Figure 1)   The patients with decreased LV GLS had larger LV end-systolic dimensions and volumes and lower LVEFs. RV free wall strain was significantly lower in patients with reduced LV GLS. (ventricular-ventricular interaction) There were no differences in functional valvular status.   The primary and secondary endpoints occurred in 14 (9.3%) and 62 (41.1%) patients, respectively. Baseline RV free wall LS and LV GLS were significantly associated with the primary endpoint and also with the secondary endpoint.   Survival was significantly better in patients with higher strain values with regard to both the primary and secondary endpoints. (Figure 2)   Conclusion: This study shows that myocardial deformation is important in determining prognosis in patients with repaired ToF.  Baseline longitudinal strain of either the left or right ventricle was significantly lower in patients who died or developed heart failure. Strikingly, apical rotation and NYHA functional class II were the only variables that were independently associated with the secondary endpoint in the multivariate model after correction for several clinical and echocardiographic variables known to be associated with outcome. Limitations: As mentioned in the article being as single center study, may have led to inclusion bias and limited numbers.  Moreover, comparing echocardiography myocardial deformation mentioned in the current study would be better compared with well-studied parameters from MRI as ventricular volumes and functions particularly for RV.   Also, though patients claim to be “asymptomatic” , many may lead a sedentary lifestyle - exercise capacity measured by exercise test parameters such  as METS and VO2 max would therefore be of greater help to correlate with myocardial deformation.

Relation Between Exercise Capacity and Extracardiac Conduit Size in Patients with Fontan Circulation. Lee SY, Song MK, Kim GB, Bae EJ, Kim SH, Jang SI, Cho SK, Kawk JG, Kim WH, Lee CH, Kim HJ, Kim J. Pediatr Cardiol. 2019 Dec;40(8):1584-1590. doi: 10.1007/s00246-019-02190-4. Epub 2019 Aug 31. PMID: 31473799 Similar articles Select item 31471627   Take Home Points: Conduit size is one of the determinants of preload in an extracardiac Fontan circuit. Its affect onto exercise capacity is independent of gender, age of Fontan operation, ventricular morphology, isomerism and the presence of fenestration in the Fontan circuit. Patients in the study demonstrated highest exercise capacity when the conduit size is 12.5mm/m2 Based on the calculation above, the optimum conduit size should be 16-18mm.               Commentary from Dr. M.C. Leong (Kuala Lumpur), section editor of ACHD Journal Watch:  In extracardiac Fontan, the conduit size is one of the key factors that determines the preload to the Fontan circuit. Larger conduit may cause flow energy loss and increase the risk of thrombosis due to stagnation of blood flow. Meanwhile, smaller conduit may increase the flow resistance. In this study, the authors sought to determine the optimal size of extracardiac Fontan conduit by comparing exercise capacity with each conduit size to see which yielded the best exercise capacity. 150 patients (male: female = 97:53; mean age :17.5 ± 5.1 years) who had undergone extracardiac Fontan completion was retrospectively reviewed. All these patients underwent cardiopulmonary exercise with expiratory gas analysis using Bruce protocol. Invasively measured central venous pressure was 12.4 ± 2.5mmHg while the pulmonary vascular resistance was 1.2 ± 0.5 Woods unit. Non-linear association between conduit diameter per body surface area (BSA) and predicted peak VO2 was computed. The authors found maximum peak VO2 at about 12.7mm/m2 conduit diameter. VE/VCO2 was lowest at 12.4mm/m2 conduit diameter and that patients had maximum exercise capacity when the conduit diameter is 12.5mm/m2 (Figure 1). This was not affected by gender, the age of Fontan operation, ventricular morphology, isomerism and the presence of fenestration in the Fontan circuit (Table 3). The authors found that conduit size 16 and 18mm to be optimal, taking into account that a body surface area of 1.57m2 in a normal adult (1.57 x 12.5mm). They also noted that although 16mm and 24mm conduit are 4mm different from a 20mm conduit in terms of diameter, the area difference is not proportional to the difference in the diameter change (Figure 2). Area difference is less if a smaller conduit is used. The authors, therefore cautioned the use of bigger conduits when fashioning the extracardiac Fontan circuit. Often, surgeons prefer a larger conduit over a smaller one to give allowance for growth. Unfortunately, such a decision may lead to a poorer exercise capacity, which presumably due to a higher flow energy loss and a lower preload. This paper has elegantly demonstrated so.  

Long-term mortality and cardiovascular burden for adult survivors of coarctation of the aorta. Lee MGY, Babu-Narayan SV, Kempny A, Uebing A, Montanaro C, Shore DF, d'Udekem Y, Gatzoulis MA. Heart. 2019 Mar 28. pii: heartjnl-2018-314257. doi: 10.1136/heartjnl-2018-314257. [Epub ahead of print] PMID:  30923175 Similar articles   Take Home Points: Large retrospective, single-centre analysis of the contemporary outcomes of patients following coarctation (CoA) repair. Initial cohort comprised 834 patients aged >16 years old. The median age of repair was 4 yrs. old (95% CI 1 month-15 years old). In 83% (n=690) repair was surgical and the remainder, percutaneously. 60% of surgical repairs were performed pre 1990 and 58% were end-to end anastomotic type. Median follow up 27 years. Deaths occurring >30 days (‘late’) after CoA repair occurred in 5% of patients (n=38). Almost a third (n=246) needed >an aortic arch intervention (n=234); 111 required an aortic valve intervention and 43 needed an ascending aortic intervention. In 59% of patients, (n=284/474) a residual pressure drop (>25mmHg) or repair site/diaphragm ratio < 70% was seen at latest follow up. A high burden of hypertension in the cohort - 70% of patients with available data were hypertensive (n=379/661) or prehypertensive (83/661). Survival in patients with a history of CoA was 99%, 88% and 65% at 30, 50 and 70 years of age – the standardised mortality ratio was 3.20 compared to age/sex matched normal subjects.         Commentary by Dr. Damien Cullington (Leeds to Liverpool), section editor of ACHD Journal Watch:  Patients with coarctation of the aorta (CoA) are common attendees in the ACHD outpatient clinic and so they will continue to be so with ever increasing frequency as the congenital cardiac population ages. Although complications can certainly ensue, if patients are managed assiduously and in line with guidelines/good practice, many complications may be treated and potentially avoided. This was a large retrospective review from the UKs largest ACHD centre but variations in outcome will occur even between centres depending on the baseline complexity/comorbidity of the cohort and interventions performed and their ‘success’. Previously, dire outcomes (i.e. >25% mortality) within 3 decades of CoA repair have been reported. This study reappraises matters and contemporarily reports on current survival and other secondary outcomes. The patient characteristics are shown in table 1. At latest follow up, 796 patients were alive – median age 33 years. The median age of CoA repair was 4 years old which is explained by a heterogeneous cohort of patients presenting at variable times with their CoA. Median age at surgical repair was relatively late compared to present day – only 36% (n=304) had CoA repair in the first year of life. A third of patients (n=276) were operated on in the very early surgical era (1947-79) which will impact on outcomes due to other covariates not accounted for in the analysis. End-to-end anastomotic repair was performed in 58% (n=397). Median follow up was 27 years (18-36 years) from repair. Of those with available data (n=661), over half of patients (n=375) who were alive and under follow up had hypertension, albeit when measured in the clinic setting. Of all patients alive, over a third are prescribed antihypertensive medication (289/796) but it seems only a minority treated attain normotension. 38 patients have died with a median age of 46 years old (37-62 years). The commonest cause of demise was LV failure (n=10). Almost a third (n=11) of patients died due to non-cardiac or uncertain cause. Independent predictors of worse survival in the multivariable analysis were presence of VSD (HR 2.97 (95% CI, 1.21-7.27, p=0.017); LVOT obstruction HR 3.11 (95% CI, 1.01-9.52, p=0.047) and requirement for an ‘associated cardiac procedure’, HR 2.57 (95% CI, 1.00-6.57, p=0.048). Reinterventions Overall, 39% (n=328) of patients required > 2 re-interventions on the arch e.g. for residual/re-coarctation, aneurysm repair or revision of previous surgery. The majority of patients in this re-intervention cohort (n=246) only required one further re-intervention and most were performed percutaneously (n=156). Freedom from second arch re-intervention was 71% (95% CI:68-74) at 30 years and 47% (95% CI 37-57) at 60 years after CoA repair (Figure 2). Independent risk factors for re-intervention were patients with LVOT obstruction at the time of CoA repair, age <1 year old at time of repair, initial percutaneous repair and initial surgical patch repair.  At least one aortic valve intervention was required in 13% of the cohort (n=111). A bicuspid aortic valve was present in 58% of the cohort (n=485). Aortic valve replacement was required most commonly (n=62). Less frequently, ascending aortic intervention was required (n=43) –usually for root or ascending aortic dilation. Figure 3 shows freedom from aortic valve or ascending aortic intervention.     Conclusions This analysis confirms, yet again, that patients even with a relatively simple ACHD lesions like CoA, are not fully ‘fixed’ and require structured, lifelong surveillance – preferably by ACHD teams versed in the complications that can ensue. Outcomes will inevitably reflect baseline complexity of anatomy, co-morbidities and the success and choice of initial intervention. Survival is much lower compared to age and sex matched normal subjects and whilst the survival and secondary outcomes described are ‘contemporary’, they probably will not reflect the long-term outcomes of present day practice.  

Mechanism and Risk Factors for Death in Adults With Tetralogy of Fallot. Egbe AC, Kothapalli S, Borlaug BA, Ammash NM, Najam M, Bajwa N, Tarek K, Matthew J, Connolly HM. Am J Cardiol. 2019 Jun 7. pii: S0002-9149(19)30627-7. doi: 10.1016/j.amjcard.2019.05.048. [Epub ahead of print] MID: 31272701 Similar articles   Take Home Points: Annual event rate of death or cardiac transplant was 0.9 % in a Mayo Clinic cohort of 465 TOF patients. Six independent risk factors associated with death/transplant were age > 42 years, atrial fibrillation, ³moderate QRS fragmentation, LVEF < 50 %, RVEDP > 16 mmHg, and LVEDP > 16 mmHg. Nearly two-fold increased risk of death or transplant per unit increase in number of risk factors.   Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:  The aim of this retrospective analysis from the Mayo Adult Congenital Heart Disease database of 465 adults with repaired TOF was to identify risk factors for death and/or cardiac transplantation. Patients’ electronic medical records were interrogated to collate data of patient demographics, co-morbidities, medications, heart rhythm, echocardiograms, cardiopulmonary exercise testing, cardiac magnetic resonance imaging, and cardiac catheterization. Data from the first visit and test/procedure was used as the baseline variable. Full datasets were not available for all patients, with a single conditional imputation method used to correct for missing data in the multivariate analysis. Baseline age was 37 ± 14 years, 48 % men, and mean age at time of TOF repair was 5 (3 – 10) years. A transannular patch repair was performed in 37 % of the cohort. The endpoint of death and/or transplant occurred in 57 (12%) patients during a follow-up of 13.6 ± 8.2 years, giving an event rate of 0.9 % per year. Mean age at death (54/57 patients with combined endpoint) was 57 ± 15 years; key causes of death included: congestive cardiac failure 23 (43%) arrhythmic/sudden cardiac death in 14 (26%) malignancy in 5 (9%), sepsis/multisystem organ failure in 4 (7%) postoperative death following cardiac surgery in 3 (6%)   Three underwent cardiac transplantation at a mean age of 54 ± 5 years, with one dying 13 months later. A multivariate risk model (Table 3, below), incorporating all statistically significant univariate correlates, identified the following risk factors: age >42 years (HR 1.86, 95% CI 1.24 to 2.03), atrial fibrillation (HR 1.84, 95% CI 1.06 to 3.17), ≥moderate QRS fragmentation (HR 1.92, 95% CI 1.47 to 2.81), left ventricular ejection fraction <50% (HR 1.39, 95% CI 1.08 to 2.31), right ventricular end-diastolic pressure >16 mm Hg (HR 1.41, 95% CI 1.02 to 1.22), and left ventricle end-diastolic pressure >16 mm Hg (HR 1.32, 95% CI 1.11 to 1.89). Each independent risk factor was assigned one point; of the original 465 patients, 208 (45 %) had no risk factors (0 points), 191 (41 %) were low risk (1-2 points), 59 (13 %) were of intermediate risk (3-4 points), and 7 (1.5 %) were at highest risk (5 or 6 points). Using the patients without risk factors as the reference group, the annual event rate rose incrementally for each additional risk factor (no risk factors, 0.2 % per year; low risk group 1.0% per year; intermediate risk group 2.7% per year; and the high risk group 4.6% per year); see figure 1 (below). A number of risk factors have previously been described in association with TOF and either all-cause death or sudden cardiac death; examples include the Khairy score which incorporates six risk factors (prior palliative shunt, inducible sustained ventricular tachycardia (VT) during electrophysiology study, QRS duration ≥180 msec, ventriculotomy incision, non-sustained VT, and left ventricular end-diastolic pressure (LVEDP) ≥12 mmHg), and the INDICATOR multi-centre study (right ventricular hypertrophy, right ventricular hypertension, left ventricular dysfunction, and atrial arrhythmia). Not exclusive to TOF, VO2peak parameters have also been demonstrated to carry prognostic information in relation to all-cause mortality in ACHD. Interestingly, the current study only found elevated LVEDP to be an independent risk for death/transplant and not any other of the Khairy score parameters, while neither VO2peak or VE/VCO2 were associated with death or transplant. Contradictions in significant risk factors identified may reflect different population groups studied, and it should be noted that the current study did not have all invasive haemodynamic, exercise, or CMR data. Nonetheless, it offers a relatively straightforward framework of risk factors to consider in the broader TOF population which is less reliant on invasive measurements/procedures such as the Khairy score.

Heart or heart-lung transplantation for patients with congenital heart disease in England. Dimopoulos K, Muthiah K, Alonso-Gonzalez R, Banner NR, Wort SJ, Swan L, Constantine AH, Gatzoulis MA, Diller GP, Kempny A. Heart. 2019 Apr;105(8):596-602. doi: 10.1136/heartjnl-2018-313984. Epub 2019 Jan 12. PMID:  30636220 Take Home Points: Retrospective analysis of patients with congenital heart disease who underwent heart or heart-lung transplantation between 1997-2015 in England, UK. Over an 18 year period, in 444 patients, there were 469 transplants - 83% heart and the remainder heart-lung. The majority of first heart or heart lung transplants were performed in patients <18 yrs. old (53%). The median age at transplantation was 19.5 years (range 0-63.6 years) Just over half of all transplants (54%, n=239) were in patents with complex congenital heart disease. Of patients undergoing heart-lung transplantation, 92% had complex congenital heart disease. Comparatively, of those patients undergoing heart transplant alone, 46% were complex and the remainder mild or moderate. Older age and heart-lung transplant were strong predictors of death. Although there is an increasing need for transplantation in the congenital cardiac population there is a supply-demand mismatch, which is ever widening. Commentary by Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch:  Heart failure is the leading cause of demise in the adult congenital cardiac population. Surgical, interventional, device and medical treatments have become ever more ambitious and proactively pursued both by clinical teams. Naturally, there is an ever increasing number of ACHD patients who are palliated for their condition and who eventually need assessment for their suitability for advanced heart failure therapies. The biggest difficulty we are facing is an adequate supply of donor organs for the ever increasing demand in the congenital population. In addition, for our patients with a Fontan, there is the further complex issue of the potential for heart-liver transplantation due to insidiously progressive Fontan associated liver disease. Dimopoulos et al. published this UK retrospective analysis of the Hospital Episode Statistics database of all patients with a code for congenital heart disease who have underwent heart or heart-lung transplant between 1997-2015 in England. The baseline characteristics of the population are shown in Table 1. The annual number of heart and heart-lung transplants performed and the age distribution at the time of transplant is shown in Figure 1. Transplant numbers and projections for the future Figure 1 shows that following an unexplained drop in transplant numbers in 2003, there has been and increasing number of heart transplants with a declining number of heart-lung transplants. The proportion of adult-to-paediatric transplants is essentially unaltered over time. Over the next decade, it is projected that there will be an increase by about a third of the number of heart and heart-lung transplants (Figure 2A). Figure 2B demonstrates the clearly evolving supply-demand mismatch between 2004-14 of an increasing number of AHCD patients hospitalised with heart failure with no corresponding increase in the number of transplants. Survival post transplantation (Figures 3A and 3B)   In the combined heart and heart-lung first transplant population (n=444), over a median follow up of nearly 5 years, 29% of patients (n=130) died.  In patients who had only a heart transplant, 30 day, 1, 5 and 10 year mortality was  11%, 14%, 21% and 27% respectively. At the same time interval, for patients undergoing heart-lung transplantation, mortality was  19%, 30%, 38% and 55%. Interestingly, for patients undergoing heart transplant, the complexity of congenital heart disease had no significant influence on survival.  From the immediate time of transplant, children (<18 years old) had better survival than adults (15 year survival 67% vs 53%, p=0.01). In survivors after one year, there was no significant difference in survival between children or adults after transplant  74% vs 66%, p=0.66). Figures 3A and 3B show Kaplan-Meier curves for patients undergoing heart and heart-lung transplant from the time of transplant as baseline and 1 year following transplant as baseline.  

Myocardial blood flow and cardiac sympathetic innervation in young adults late after arterial switch operation for transposition of the great arteries. Possner M, Buechel RR, Vontobel J, Mikulicic F, Gräni C, Benz DC, Clerc OF, Fuchs TA, Tobler D, Stambach D, Greutmann M, Kaufmann PA. Int J Cardiol. 2019 Jul 13. pii: S0167-5273(19)32420-9. doi: 10.1016/j.ijcard.2019.07.041. [Epub ahead of print] PMID: 31337551 Similar articles Select item 30252328 Take Home Points: Disruption of cardiac sympathetic innervation occurs to a variable degree following the arterial switch operation. This small study sought to evaluate sympathetic innervation in young adults after the arterial switch procedure and assess myocardial blood flow at rest and during stress. The study group consisted of 12 patients (age 22.5 +/- 2.6 years) who previously underwent an arterial switch operation and 10 ‘normal’ control subjects (age 22 +/- 1.7 years). PET scanning assessed cardiac sympathetic innervation at rest and under stress. Patients with a previous arterial switch, compared to normal subjects had attenuated sympathetic innervation. Global myocardial blood flow during rest and stress was lower in ASO patients compared to control subjects.  Commentary from Dr Damien Cullington (Liverpool, United Kingdom), section editor of ACHD Journal Watch:  The arterial switch operation (ASO) was first performed in 1975 by Jatene and superseded the atrial switch with ever increasing frequency from the 1980s. So far, outcomes are very good but, there are important issues which ever increasingly crop up, for example, the dimensional threshold at which to contemplate neo-aortic root replacement (where benefit >risk) and the risk stratification (how and with what frequency) of patients who have kinked re-implanted coronary arteries. Cardiac sympathetic fibres travel with the coronary arteries and the ASO often results in denervation which may consequently alter regulation of myocardial blood flow (MBF). Little has been studied about sympathetic innervation and MBF in adult patients who have undergone the ASO, hence the purpose of this study.  Assessment of sympathetic innervation and myocardial blood flow On day one, myocardial blood flow was measured using [15O] H2O PET. Assessments were made at rest, after adenosine stress and following a cold pressor test. On day two, cardiac sympathetic innervation was measured using [11C] meta-hydroxyephedrine (mHED) PET. [11C] mHED is an analogue of norepinephrine – highly specific for pre-synaptic sympathetic nerve terminals. Coronary computed tomography angiography (using a 256 slice high resolution CT scanner) was performed in all patients after mHED PET. Full details of the analysis and calculation of MBF is found in the main text of the article.  Myocardial blood flow at rest and stress (Figure 1 and Table 1) and cardiac sympathetic innervation MBF at rest and during adenosine stress was significantly lower in patients with ASO vs healthy controls. No difference in MBF was seen during the cold pressor test. Global [11C] mHED uptake was significantly lower in patients with ASO vs controls (p<0.001).   Table 1 – Myocardial blood flow at rest and during adenosine stimulation and during cold pressor test in patients and controls  Figure 1 – Myocardial blood flow in healthy controls and patients after ASO at rest and during adenosine-induced hyperaemia (A) and at rest and during cold pressor test (B). Comparison of cold pressor test induced myocardial blood flow (C) and mHED uptake (D) between healthy controls and patients.  Conclusions The ASO procedure leads to attenuated cardiac sympathetic innervation. MBF response to cold pressor testing did not differ between ASO patients or controls. This is a small study which confirms similar findings in children. Further, large observational studies are needed to assess the natural history and long terms outcomes of patients who undergo the ASO.  

Echocardiographic predictors of elevated left ventricular end diastolic pressure in adolescent and adult patients with repaired tetralogy of Fallot. Lubert AM, Cotts TB, Zampi JD, Yu S, Norris MD. Cardiol Young. 2019 Aug;29(8):1020-1024. doi: 10.1017/S1047951119001331. Epub 2019 Jun 18. Echocardiographic predictors of elevated left ventricular end diastolic pressure in adolescent and adult patients with repaired tetralogy of Fallot. Lubert AM, Cotts TB, Zampi JD, Yu S, Norris MD. Cardiol Young. 2019 Aug;29(8):1020-1024. doi: 10.1017/S1047951119001331. Epub 2019 Jun 18. PMID: 31208473 Similar articles Select item 31067002   Take Home Points: Elevated LVEDP is a risk factor for ventricular arrhythmias in patients with Tetralogy of Fallot. Small retrospective study of patients >13 yrs old (n=94) who had a left heart catheter within 7 days of TTE. Univariable comparison made between TTE and clinical variables in patients with LVEDP >12mmHg and <12mmHg. Patients with LVEDP >12mmHg were older, more likely to have a history of aortopulmonary shunt and hypertension compared to patients with an LVEDP < Patients with LVEDP >12mmHg have larger left atrial areas (mean 17.7 vs 14 cm2, p=0.03). No significant differences in E/A ration, annular e’ velocity, or E/e’ ratio between patients with LVEDP >12mmHg vs < In this small study in patients with TOF, typical measures of diastolic dysfunction on TTE were unreliable in predicting patients who had elevated LVEDP. Larger prospective studies are required to investigate this further. Commentary from Dr. Damien Cullington (Liverpool, United Kingdom), section editor of ACHD Journal Watch:  LVEDP has been shown to be a risk factor for ventricular arrhythmias and worse survival in patients with TOF. The only sure-fire way to measure LVEDP is to perform a cardiac catheter study - obviously this is an invasive test requiring significant resources to perform. For some patients, it is unpleasant plus anxiety provoking so any way of avoiding would be preferable. Over decades of research, mostly in the non-congenital cardiac population, a number of echocardiographic measures have been investigated as surrogate measures of raised LVEDP such as E/A, E/e’ and LA volume. This small retrospective study sought to correlate non-invasive TTE measures of raised LVEDP with direct catheter measurement in a group of young patients with tetralogy of Fallot. Compared with other analyses, in the non ACHD population, LVEDP measured by catheter did not seem to correlate with usual surrogates of LVEDP measured on TTE. It is unknown how many patients with TOF have elevated LVEDP on catheter but normal TTE diastology indices. This analysis collated data over 16 years (2001-2017) in patients > 13 years old with TOF or pulmonary atresia with VSD. All patients had a TTE within 7 days of a cardiac catheter study. The clinical characteristics of the cohort are shown in Table 1. Salient points to note from the clinical characteristics of the cohort are that almost half of patients had had an aorto-pulmonary shunt and 60% had a transannular patch with 18% having experienced ventricular arrhythmias. A quarter of patients required loop diuretics suggesting these patients had established heart failure. The characteristics differ from a contemporary cohort of TOF patients whom would have far fewer numbers of patients with transannular patches and shunts. Just over a third of patients (n=34) had an LVEDP >12mmHg. Univariable factors associated with LVEDP >12mmHg were age, weight, previous aortopulmonary shunt, a pacemaker and hypertension – Table 2.   The most reliable predictors of a LVEDP >12mmHg were measures of LA size - Doppler measures, were not. There is fertile ground here for further investigation, ideally with a much larger sample size. Over half of the patients with a LVEDP >12mmHg had severe PR plus proportionally greater numbers with > moderate TR. It would certainly be of interest to understand the influence of PR on LVEDP and whether in patients who had undergone PVR had lower LVEDPs.  

Creatinine versus cystatin C to estimate glomerular filtration rate in adults with congenital heart disease: Results of the Boston Adult Congenital Heart Disease Biobank. Opotowsky AR, Carazo M, Singh MN, Dimopoulos K, Cardona-Estrada DA, Elantably A, Waikar SS, McCausland FR, Veldtman G, Grewal J, Gray C, Loukas BN, Rajpal S. Am Heart J. 2019 Aug;214:142-155. doi: 10.1016/j.ahj.2019.04.018. Epub 2019 May 22. PMID: 31203159 Similar articles Select item 31204032   Take Home Points: Chronic kidney disease, defined by reduced estimated glomerular filtration rate (eGFR), is associated with worse prognosis, and is common among adults with congenital heart disease compared to similarly aged peers eGFR calculations using creatinine can be inaccurate when actual muscle mass differs from expected population-based norms, as is seen in some adult CHD subjects – especially the single-ventricle Fontan population In a heterogenous cohort of 911 adults with CHD, cystatin C-based eGFR (CKD-EPICysC) classified a larger proportion of patients as having moderate or severely reduced eGFR as compared to creatinine-based eGFR (CKD-EPICr) CKD-EPICrtended to overestimate eGFR in the low to mid-range and underestimate eGFR at the higher end of the range, compared with CKD-EPICysC Cystatin C-based eGFR better predicted all-cause mortality, and the composite of death or non-elective cardiovascular hospitalization. In the single-ventricle Fontan circulation subset there was poor agreement between creatinine-based and cystatin C-based eGFR. Measurement of cystatin C to better estimate eGFR should be considered in those with mildly reduced eGFR, and single-ventricle Fontan circulation patients.   Commentary from Dr. Timothy Roberts (Melbourne), section editor of ACHD Journal Watch:  The aim of this study was (1) to determine the correlation and agreement between various eGFR equations and (2) to compare the prognostic value of creatinine and cystatin C-based eGFR equations. The primary outcomes of interest were (1) all-cause mortality and (2) a composite outcome of either all-cause mortality or non-elective cardiovascular hospitalization. Adult patients were recruited from Boston Children’s or Brigham and Women’s Hospitals between 2012 – 2017. Patients were classified into different CHD pathophysiologic groups, New York Heart Association (NYHA) functional class, presence of cyanosis, diagnosis severity, and the presence of a single-ventricle versus biventricular circulation. Average age was 38.6 +/- 13.6 years, and 49.2 % were female. The majority (78.3 %) of subjects had moderate or severe complexity of CHD. The most common underlying diagnoses were: left-sided obstructive lesions (n=200, 22.0%), tetralogy of Fallot (n=187, 20.5%), single-ventricle physiology with a Fontan palliation (n=131, 14.4%), simple shunt lesion without clinical sequelae (n=122, 13.4%), and transposition of the great arteries with a systemic right ventricle (n=84, 9.2%). Hypertension was present in 144 (14.6%) and diabetes in 38 (4.6%) patients. The prevalence of chronic kidney disease according to eGFR is shown below in Figure 1 using various equations:   GFR category was classified differently in 228 of the 911 patients by the CKD-EPICr and CKD-EPICysC equations. For both CKD-EPI equations, lower eGFR was associated with older age, higher BMI, hypertension, diabetes, atrial arrhythmias, pulmonary hypertension, cyanosis, and functional class. Average eGFR was similar for both CKD-EPI methods, however there was heterogeneity between different types of CHD. In particular, in the 131 patients with a single-ventricle Fontan circulation, creatinine-based eGFR was, on average, 10.3 +/- 19.3 higher with 95 % limits of agreement -28.2 to +48.8 ml/min/1.73 m2. For both single-ventricle Fontan and biventricular circulations, CKD-EPICr tended to overestimate eGFR in the low to mid-range and underestimate eGFR at the higher end of the range, compared with CKD-EPICysC. In univariate analysis, there was a higher risk for both all-cause mortality and the composite outcome for patients categorized in the lowest eGFR category for all eGFR equations. There was a clear stepwise increase in risk for adverse outcomes across the 3 eGFR categories for CKD-EPICysC (figure 4, below). Multivariate adjustment was not performed for all-cause mortality due to low event numbers (n=34, 3.1%); however, for the composite outcome, only the CKD-EPICysC eGFR category remained a significant predictor on multivariate analysis. In the single-ventricle Fontan circulation cohort, higher CKD-EPICysC eGFR was associated with lower risk of the composite outcome (41 events in 131 patients; HR = 0.85 [0.76-0.95], P=0.005, C-statistic 0.652) whereas neither of the purely creatinine-based eGFR methods was significantly associated with the risk of the composite outcome.   The authors conclude that more accurate identification of renal dysfunction could enable earlier intervention targeted at mechanisms of kidney disease, more appropriate drug dosing for renally cleared cardiovascular medications, assessment of risk when using iodinated contrast media for CT and catheterization, identification of patients at highest risk for acute kidney injury after surgery involving cardiopulmonary bypass, and more informed consideration during heart transplant evaluation. It should be noted that cystatin C levels can be affected by other variables which were not assessed in the current study. Only a single measurement was considered, without factoring in the time since surgery nor changes on repeated measurements. The cost-benefit balance of measuring cystatin C is also unclear. Nonetheless, the study ultimately raises concern for the reliance on creatinine-based eGFR calculations, especially for single-ventricle Fontan circulation patients.  

Relation of Magnetic Resonance Elastography to Fontan Failure and Portal Hypertension. Alsaied T, Possner M, Lubert AM, Trout AT, Szugye C, Palermo JJ, Lorts A, Goldstein BH, Veldtman GR, Anwar N, Dillman JR. Am J Cardiol. 2019 Aug 7. pii: S0002-9149(19)30883-5. doi: 10.1016/j.amjcard.2019.07.052. [Epub ahead of print] PMID: 31474329 Similar articles Select item 31400339   Take Home Points: Magnetic resonance elastography (MRE) is a non-invasive method of assessing liver stiffness and liver fibrosis. In this study of 70 adult Fontan patients, all had increased MRE liver stiffness (greater than 2.9 kPa is the cutoff used as this institution). Liver stiffness of 4.5 kPa or greater is associated with Fontan failure (sensitivity of 77% and specificity of 77%) and radiologic signs of portal hypertension (sensitivity of 69% and specificity of 65%). MRE-derived liver stiffness is associated with adverse hemodynamics, liver function, and clinical outcomes in Fontan circulation. Commentary from Dr. Maan Jokhadar (Atlanta GA), section editor of ACHD Journal Watch:   Fontan associated liver disease (FALD) is associated with Fontan failure (FF) and appears to be multifactorial with contributing factors that include elevated central venous pressure and chronic liver congestion, low cardiac output, abnormal liver lymphatic drainage, and other factors. Assessing FALD and FF with liver biopsy is of limited reliability due to the non-uniform nature of fibrosis in this population. Noninvasive assessment of liver stiffness including magnetic resonance elastography (MRE) has shown mixed results. Dr. Alsaied and colleagues from the University of Cincinnati performed a retrospective cohort analysis of 70 adult Fontan patients who were evaluated between 2012 and 2018 to determine the role of MRE as a measure of liver stiffness and its relationship to hemodynamics, liver enzymes, portal hypertension, and FF. In this study, FF was defined as death, heart transplant listing, or heart failure symptoms requiring escalation and diuretic therapy. The upper limit for normal liver stiffness at this institution is 2.9 kPa. The median age was almost 25 years and 52% were men. The median follow-up from the time of MRE was 3.9 years. There is no significant correlation between MRE liver stiffness and age or time since Fontan. There was one case of hepatocellular carcinoma detected with MRE screening. There was a moderate negative correlation of liver stiffness with ventricular ejection fraction and ventricular end diastolic volume. Patients with moderate to severe atrioventricular valve regurgitation had significantly higher liver stiffness compared to patients with no or mild regurgitation. Also, patients with a history of thromboembolism had higher liver stiffness compared to patients without prior thromboembolism. There was a very mild positive correlation between liver enzyme elevations and liver stiffness. There was no difference in laboratory values in patients with or without FF. Patients with features of portal hypertension including splenomegaly, varices, or ascites had higher liver stiffness compared to patients without these features. Liver stiffness had a weak negative correlation with platelet count. Using ROC analysis liver stiffness had an area under the curve of 0.69 to differentiate portal hypertension and it should be noted that liver stiffness above 4.5 K PA differentiated portal hypertension with the sensitivity of 69% and specificity of 65%. FF was present in 19 patients (4 deaths, 1 heart transplant, and 8 with worsening heart failure, 1 of whom received LVAD.  FF patients had higher liver stiffness. A liver stiffness above 4.5 kPa differentiated FF with sensitivity of 77% and specificity of 77%. All adult Fontan patients in this study had increased liver stiffness by MRE and this correlated with increased Fontan pressure, lower ventricular ejection fraction, atrioventricular valve regurgitation severity, FF, elevated liver enzymes, and radiologic signs of portal hypertension. Liver stiffness in FALD is a function of both congestion and fibrosis and this may explain previous studies showing discrepant data regarding the correlation of MRE and biopsy measures of fibrosis. In contrast with previous studies, this study of adult Fontan patient showed that MRE liver stiffness was not associated with time since Fontan. The study authors suggest that MRE could be used routinely in Fontan patients as part of routine assessment cardiac and liver “health”, which could be used as a global assessment of the Fontan circulation that correlates with the development of clinical symptoms and outcomes. Abnormal MRE liver stiffness could then trigger more detailed evaluation. Additional prospective, multi centered studies with longer serial follow-up and changes with medication and/or intervention are needed before recommending routine MRE surveillance for Fontan patients. using this technique. Cost effectiveness should also be considered.

The long-term functional outcome in Mustard patients study: Another decade of follow-up. Srivastava NT, Hurwitz R, Kay WA, Eckert GJ, Kuhlenhoelter A, DeGrave N, Ebenroth ES. Congenit Heart Dis. 2019 Mar;14(2):176-184. doi: 10.1111/chd.12698. Epub 2018 Nov 23. PMID:  30468301 Similar articles  Take Home Points: Cardiac mortality (death or transplant) is high in D-TGA patients treated with the Mustard atrial switch procedure, followed longitudinally over several decades, with half of the events occurring after age 25. The majority of deaths were due to systemic RV failure rather than sudden cardiac death. 3/8 patients with sudden cardiac death (excluding those post-transplant) had no prior history of arrhythmia during routine follow up. Systemic RV function showed a progressive decline over longitudinal follow up, whereas sub-pulmonary LV function was maintained. The majority of patients demonstrated some degree of arrhythmia. Few patients required pacemaker due to sinus node dysfunction/sick sinus syndrome beyond 2-3 decades post-surgery. General health, physical function and energy were significantly reduced in quality of life questionnaires. There was no single clear predictor for worse outcomes in D-TGA Mustard patients, although deteriorating RVEF is associated with mortality and transplantation.   Commentary from Dr. Timothy Roberts (Melbourne), section editor of ACHD Journal Watch:  This longitudinal cohort study from the Indianapolis group provides an update on the outcome of D-TGA Mustard patients over two decades after their atrial switch operation. A total of 45 patients were originally included for assessment between 1993-97 (Time 1), with 35 agreeing to be included approximately 10 years later (Time 2). In the current follow up assessment performed between 2013-17 (Time 3), 25 of the original 45 participants data are included (figure 1, below). This group comprises 16 males and 9 females, at a mean age of 36.7 +/- 4.9 years (29 – 49 years), 34.3 +/- 3.9 years post original Mustard repair.   Figure 1.   Testing involved a standard Bruce protocol treadmill cardiopulmonary exercise test (CPET), echocardiography, Holter monitor with rhythm history, and quality of life questionnaire. Cardiac function and anatomy were assessed by cardiac MRI or cardiac CT, rather than radionuclide angiocardiography as was performed in the original study. Mortality at any time point after recruitment (Time 1) was 22% (10/45 patients). Four of these (9%) occurred between Time 1 and Time 2, while a further six (13%) died between Time 2 and Time 3. Six patients underwent cardiac transplantation, two prior to, and four after, Time 2. Two of these transplant patients subsequently died of acute rejection, leaving a total of 14 patients (31%) of the original patient cohort experiencing cardiac death (mortality, cardiac transplantation, or both). Fifteen (63%) of 23 patients with rhythm data available demonstrated some form of continued rhythm disturbance. Seven of the 23 had required pacemaker insertion for sick sinus syndrome or complete heart block, however only one required pacing between Times 2 and 3. Five (23%) had undergone cardioversion, and 5 (23%) required EP study for either supraventricular or ventricular tachycardia. Exercise time and workload (METS) reduced significantly between Time 1 and 2, but no further significant reduction was observed in the follow decade (figure 2). VO2peak reduced from 28 (+/- 6.7) ml/kg/min to 23.6 (+/- 7.8) ml/kg/min between Time 2 and 3, which did not meet statistical significance and furthermore data corrected for age-predicted measures (noting the 10-year period between results) was not provided. Maximum predicted heart rates did not differ over the three time points, although they were lower than would be expected for a healthy cohort. Figure 2. Cardiac CT or MRI was performed in 34/35 subjects at Time 2, and 18/25 subjects most recently. RVEF decreased significantly to 45% (+/- 11%) vs. 53% (+/- 10%) at Time 2 (P=0.011). LVEF was unchanged (62 +/- 8% vs. 62 +/- 8%; P=0.868). Subjective assessment of RV function by echocardiography was made in 21/25 patients, and compared to previous data of the same patients at Times 1 and 2. Three (14%) patients in the current study had normal RV function, compared to 26% at Time 2, and 29% at Time 1. Anatomical assessment identified 71% with patent systemic and pulmonary baffles, 14% with mild SVC baffle obstruction, and 14% with significant or severe baffle obstruction. None of the subjects with baffle obstruction had documentation of baffle obstruction in their previous assessment at Time 2. Quality of life questionnaires noted progressive decline in energy during the three Time points. General health, physical function, and energy were statistically different as compared with healthy adult norms. Additionally, scores were comparable or lower in all areas as compared to those with other forms of acyanotic congenital heart disease. The study group appropriately conclude that cardiac mortality remains high for Mustard patients over two decades of longitudinal follow-up, while systemic RVEF, exercise tolerance, and quality of life measures decline. No single predictor was identified to predict a poorer outcome, although deteriorating RVEF was associated with mortality and cardiac transplantation.

Exercise Capacity in Asymptomatic Adult Patients Treated for Coarctation of the Aorta. Dijkema EJ, Sieswerda GT, Breur JMPJ, Haas F, Slieker MG, Takken T. Pediatr Cardiol. 2019 Oct;40(7):1488-1493. doi: 10.1007/s00246-019-02173-5. Epub 2019 Aug 7. PMID: 31392380 Free PMC Article Similar articles Select item 31367952   Take Home Points: Exercise capacity was normal in a small group of adults > 20 years post repair of coarctation of the aorta. Resting hypertension was present is 59 % (13/22) while exercise-induced hypertension was detected in 82 % (18/22). Amongst normotensive subjects, exercise-induced hypertension occurred in 78 % (7/9). Surveillance of exercise-induced hypertension with cardiopulmonary exercise testing as a precursor to chronic hypertension can be considered for its early detection. Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:   Exercise capacity is reduced in adults with congenital heart disease (CHD), although those with repaired coarctation of the aorta (CoA) are thought to have the least – if any – impairment relative to other forms of complex CHD. Meanwhile hypertension remains a lifelong risk in repaired CoA, due to reduced aortic compliance, impaired baroceptor function, and abnormal wall-shear stress dynamics. Isolated exercise-induced hypertension may be a predictor for the future development of chronic hypertension. The aims of this singe centre prospective study were to assess (1) exercise capacity, and (2) blood pressure response in adults with repaired CoA in relation to left ventricular and vascular function. Study participation involved cardiopulmonary exercise testing (CPET) and cardiac MRI. Inclusion criteria were a history a CoA with primary treatment (surgical or balloon angioplasty without stenting) performed between ages 3 months to 16 years, and more than 10 years of follow-up. Exclusion criteria were isthmus or aortic arch hypoplasia, and severe associated CHD lesions. A ‘control group’ for exercise data was constructed using a large Dutch database. A total of 72 patients met criteria, of which only 22 (31 %) agreed to participate. Patient demographics, and CPET results are shown in the tables below: Exercise capacity was normal (VO2peak 41.7 +/- 12 ml/kg/min) in the CoA cohort. Exercise-induced hypertension was common (82 %), and of the 9 normotensive subjects, 7 (78 %) demonstrated exercise-induced hypertension. Peak exercise blood pressure was correlated to LV mass, 24-hour ambulatory systolic blood pressure, and systemic hypertension. Multiple regression analysis was attempted to identify predictors of VO2peak and not surprisingly identified male sex and age as significant predictors; a number of additional factors were included but the small sample size would make it highly unlikely to find additional significant associations (whilst being statistically inappropriate). This study is limited by the small sample size, low recruitment rate, inevitable risk for selection bias in an exercise-based study, and the absence of a true control cohort. Nevertheless, it does demonstrate a large proportion of normotensive repaired CoA subjects to display exercise-induced hypertension. Although the significance of such a finding remains debated, these patients may benefit from more frequent blood pressure assessments to enable earlier detection of chronic hypertension. Exercise testing to assess for exercise-induced hypertension carries a Class IIb recommendation in the 2018 AHA/ACC Guidelines for the Management of Adults With Congenital Heart Disease.

Planned vaginal delivery and cardiovascular morbidity in pregnant women with heart disease. Easter SR, Rouse CE, Duarte V, Hynes JS, Singh MN, Landzberg MJ, Valente AM, Economy KE. Am J Obstet Gynecol. 2019 Jul 13. pii: S0002-9378(19)30903-2. doi: 10.1016/j.ajog.2019.07.019. [Epub ahead of print] PMID: 31310750 Similar articles Select item 31302712   Take Home Points: There was no significant difference in cardiac complication rates in patients with planned Caesarean section versus planned vaginal delivery in pregnant women with heart disease. The highest risk patients (aortic stenosis, Marfan's) underwent planned Caesarean section or operative vaginal delivery. The complications rate was low across the board, so the study was statistically underpowered to detect a significant difference in cardiac complication rates between the two groups. Commentary from Dr. Helen Parry (Leeds UK), section editor of ACHD Journal Watch:  It is generally accepted that Caesarean section in mothers with heart disease is usually only indicated for obstetric reasons.  However, a third of mothers with cardiovascular disease end up having a Caesarean delivery.  It is also unclear whether operative vaginal delivery, designed to reduce time spent performing the Valsalva manoeuvre, actually increases rather than reduces maternal morbidity. This was a prospective study at a single centre in Boston where patents were categorised according to pathology: congenital heart disease, valvular heart disease, cardiomyopathy, connective tissue disorder or vascular disease.  They were regarded as high risk if they had 1 or more of: NYHA>II resting saturation <90% left ventricular ejection fraction <40% peak gradient through LVOT >30mmHg sub-pulmonic ventricular ejection fraction <40% aortic conditions associated with connective tissue disease   Patients were looked after by a multi-disciplinary team. Vaginal delivery was generally encouraged and patients were divided according to planned delivery mode. The primary endpoint was the development of cardiovascular complications including congestive heart failure, sustained arrhythmia, stroke, worsening valve function, endocarditis, aortic dissection, need for cardiac intervention, cardiac arrest or death.  This included complications occurring up to 6 weeks post-partum. The study enrolled 276 expectant mothers who ultimately delivered a baby.  210 of these were planned vaginal deliveries (70% of these women had congenital heart disease), 66 planned Caesarean (these patients had a greater proportion of left ventricular outflow tract obstruction, 65% of these patients had congenital heart disease).  Eighty-six per cent of the patients with planned vaginal delivery went on to deliver vaginally although 9.5% of those had operative vaginal deliveries as pushing was limited in these patients due to aortic stenosis or Marfan's.  The remaining 14% of patients with planned vaginal delivery underwent Caesarean section for obstetric reasons.  Rates of cardiac complications as defined above were similar between the 2 groups. There were a number of study limitations including the small sample size of the planned Caesarean section group, the grouping together of all congenital heart disease and the single centre nature of the study raises questions about whether results are representative.  The low cardiac complication rate in both groups means that the study was statistically under powered to detect a difference between the 2 groups.  

X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood. Fiot E, Zénaty D, Boizeau P, Haignere J, Dos Santos S, Léger J; French Turner Syndrome Study Group. Eur J Endocrinol. 2019 Jun 1;180(6):397-406. doi: 10.1530/EJE-18-0878. PMID:  30991358  Take Home Points: Turner syndrome (TS) patients with 45, X karyotype are most likely to have congenital heart disease when compared with other karyotypes TS mosaicism patients were less likely to develop comorbidities as they got older when compared with other karyotypes. Patients with a ring X chromosome were more prone to metabolic disorders. It is possible that X gene chromosome dosage, particularly for Xp genes, contributes to the risk of developing acquired comorbid conditions. Commentary by Dr. Maan Jokhadar (Atlanta), section editor of ACHD Journal Watch:  Turner syndrome (TS) as a condition in which all or part of one X-chromosome Is absent from some or all cells. TS occurs in about 1/2500 live born girls. TS is associated with congenital cardiac and renal malformations. In addition, TS is associated with increased risk of hearing loss and metabolic disease that includes obesity, dyslipidemia, hypertension, abnormal glucose metabolism, and liver dysfunction. An increased risk of autoimmune thyroid disease and celiac disease is also observed. Certain TS karyotypes may increase the associated risk of both congenital and acquired conditions. Dr. Elodie Fiot and colleagues from France conducted a national, multi-centered, observational study that included all patients with Turner syndrome diagnosed before January 2013 and followed at participating pediatric and adult centers from the French national rare disease network (the French Turner syndrome study group). The prevalence of congenital malformations and the cumulative incidence of subsequent comorbidities was evaluated at five-year intervals, from the ages of 10 to 30 years. The median age was 9.4 years at initial evaluation and 16.8 years at last evaluation with a median follow-up of 4.1 years. This was a young cohort with only about 12% over the age of 30 years at last evaluation. The TS karyotype associations with congenital malformations were as follows: 45, X (n= 549, 36%): cardiac malformations were present in 27% and renal malformations in 22% 45, X /46, iso-chromosome Xq (n= 280, 19%): cardiac malformations were present in 12.5% and renal malformations 18.9% Ring X chromosome 46, X, r(X)/ 46, XX (n= 106, 7%): cardiac malformations were present in  17% and renal malformations 20.8%. 45, X /46, XX Mosaic karyotype (n= 221, 15%): cardiac malformations were present in 13.1% and renal malformations 11.3%. Presence of Y chromosome (n= 87, 6%): cardiac malformations were present in 21.8% and renal malformations in 10.3%. Other (various mosaicism with triple X, variable Xp for Xq deletions, and various complex rearrangements or translocations within an X chromosome) (n= 258, 17%): cardiac malformation were present in  13.2% and renal malformations in 10.5%. There were 35 patients with unknown karyotype who were excluded from the study. Congenital cardiac malformations were more common with 45, X compared with other karyotypes. As one would expect, TS patients acquired comorbid medical conditions, such as hearing loss, metabolic disease, and autoimmune disease as they got older. However, patients with TS mosaicism were less likely to develop comorbidities when compared with other karyotypes. This study showed a lower prevalence of comorbidities in TS with 45,X/46,XX mosaicism or TS with a Y chromosome when compared with TS patients with a ring X chromosome or with a 45,X/46,isoXq or 45,X karyotype.  This may underscore the role of X chromosome dosage in the occurrence of comorbidities in TS patients. Patients with a ring X chromosome were more prone to metabolic disorders.

Usefulness of Red Blood Cell Distribution Width in the Assessment of Hemodynamics After Tetralogy of Fallot Repair. Kojima T, Imamura T, Osada Y, Muraji S, Nakano M, Oyanagi T, Yoshiba S, Kobayashi T, Sumitomo N. Circ J. 2019 Feb 23. doi: 10.1253/circj.CJ-18-1016. [Epub ahead of print] PMID: 30799372  Take Home Points: In this study of children undergoing routine hemodynamic assessment within a year of tetralogy of Fallot repair, higher red blood cell distribution width (RDW) was predictive of: Suboptimal hemodynamics, including higher right ventricle pressure/left ventricle pressure ratio. Elevated CVP. Lower mixed venous oxygen saturation. Increased pulmonary stenosis severity. Increased pulmonary regurgitation severity by echo. Residual ventricular septal defect. Also, RDW was particularly associated with higher reoperation risk and the RDW tended to improve after reoperation. Commentary by Dr. Maan Jokhadar (Atlanta), section editor of ACHD Journal Watch:  Red blood cell distribution width (RDW) is routinely reported as part of a complete blood count and is clinically useful for anemia evaluation. Elevated RDW is a sign of nutritional deficiency, including iron deficiency, vitamin B12 deficiency, etc. There is also a growing body of literature linking elevated RDW to worse outcomes with heart failure, coronary disease, pulmonary hypertension, and congenital heart disease, including Fontan patients.  The reasons for these associations are not clear but could be related to inflammatory stress, nutritional deficiency, and inadequate production of erythropoietin in the setting of a suboptimal hemodynamic state. Dr. Kojima and colleagues in Saitana, Japan performed a retrospective analysis of 50 children who were admitted for postoperative cardiac catheterization after surgical tetralogy of Fallot repair, which is part of routine postoperative management in this center. The mean age at the time of surgical repair was about 6.6 +/- 2.1 months (range 3 to 12 months) and cardiac catheterization was performed 11.3 +/- 9.6 months after surgery.   About 56% had transannular patch repair and about  24% had a previous palliative shunt. Ten patients had residual VSD. Seven patients had reoperation due to significant VSD in 4 patients and pulmonary stenosis in 3 patients. In this pediatric population undergoing routine hemodynamic assessment after recent tetralogy of Fallot repair, higher RDW was associated with higher right ventricle pressure/left ventricle pressure ratio, elevated CVP, lower mixed venous oxygen saturation, increased pulmonary stenosis severity, increased pulmonary regurgitation severity by echo, and residual ventricular septal defect. Also, RDW was particularly associated with higher reoperation risk and the RDW tended to improve after reoperation. Thus, RDW was associated with both right ventricle volume overload and pressure overload.  In addition, RDW appeared to be more predictive than BNP in this population. These data are an important step forward and bolster the argument that RDW may have value as part of the hemodynamic and prognosis assessment in patients with repaired tetralogy of Fallot. However, larger prospective studies are needed to better understand the role of RDW in this realm.  

Early Experience With Sacubitril/Valsartan in Adult Patients With Congenital Heart Disease. Lluri G, Lin J, Reardon L, Miner P, Whalen K, Aboulhosn J. World J Pediatr Congenit Heart Surg. 2019 May;10(3):292-295. doi: 10.1177/2150135119825599. PMID:  31084317 Similar articles Take Home Points: Congestive heart failure due to systolic heart dysfunction in ACHD patients is a common cause of early death and disability.  Many medications in the general population have copious evidence of improving outcomes in the general CHF population; however ACHD has very little evidence of any drugs working due to patient heterogeneity, small sample sizes, limited follow-up, and other issues that make a well-designed clinical trial very hard to execute. Sacubitril/valsartan is a newer FDA-approved drug in a new class known as an ARNI.  It combines an angiotensin II receptor blocker (ARB) with a neprilysin inhibitor (NI). This combination affects both the renin-angiotensin-aldosterone system (RAAS) and the natriuretic peptide (NP) systems.  This drug showed ~20% reduction in mortality compared to standard therapy in the PARADIGM-HF trial, with over 8000 patients randomized. There is limited evidence that drugs affecting the NP system may improve symptoms in patients with pulmonary hypertension and/or systemic right ventricles, which are both commonly encountered in ACHD. To date, there has been very little study of ARNI in ACHD.  This paper is the 2nd of 3 published to evaluate this topic.  This paper had 15 patients; the first paper had 4 and the most recent 23 patients under study. The study was underpowered to show statistically significant results but did demonstrate anecdotal improvement in 4/5 patients with NYHA class III symptoms and also only 1/15 (6.6%) had to stop the medication (the rate of stopping the medication was 10.7% in  PARADIGM-HF) Commentary from Dr. W. Aaron Kay (Indianapolis), section editor of ACHD Journal Watch:   Although most congenital defects can be repaired with excellent survival to adulthood, congestive heart failure due to significant systolic dysfunction is often a common final pathway leading to early disability and death in ACHD patients.  Sacubitril/valsartan, a unique drug in a novel class known as ARNIs (angiotensin receptor inhibitor combined with a neprilysin inhibitor) has recently entered the armamentarium of heart failure drugs, and although there hasn't been a lot of long-term experience with it, it has been studied in the largest heart failure trial ever, in terms of sheer volume of patients, in the PARADIGM-HF trial, which randomized over 8000 patients to ARNI versus enalapril.  That trial, in the general non-ACHD population, showed significant superiority of ARNI over enalapril; however to date there has been very little formal study of ARNI usage and outcomes in the ACHD population. This small retrospective review coming from University of California Los Angeles (UCLA) shows the entirety of their first year experience using sacubitril/valsartan. Patients included a variety of anatomic congenital heart diagnoses (2 Fontans, the rest with 2-ventricle repairs); all patients had either NYHA II or NYHA III symptoms at baseline.  Of the 15 total patients on the medication, 14 were able to tolerate it (one stopped due to renal failure).  In the PARADIGM-HF trial, ~10.7% of patients had to stop ARNI due to side effects, most commonly hypotension and hyperkalemia. The number of patients was very low, in one of the largest ACHD centers in the United States, which likely reflects the ACHD community's general reluctance to try new drugs until they have been proven safe in the larger non-CHD community, as well as issues of expense - most ACE inhibitors are available even without insurance for $4 a month, whereas sacubitril/valsartan costs more than $1000 a month without insurance. The study presented here was retrospective, and too small to have adequate power to draw meaningful statistical conclusions.  However, it is notable that that 4/5 patients with NYHA class III CHF symptoms had improvement in their degree of heart failure symptoms.  Mechanistically, it stands to reason that patients with 2-ventricle repairs and a subaortic left ventricle would be similar to the general heart failure population studied in PARADIGM-HF; however ACHD has been plagued by lack of large enough trials to prove or disprove that ACE inhibitors, ARBs, and other heart failure drugs make a significant difference in those with systemic right ventricles or single ventricles. This study is quite interesting, and perhaps when the price of sacubitril/valsartan comes down more it will be adopted more commonly in ACHD versus cheaper alternatives.  Given the lack of evidence of heart failure drugs in general in ACHD, as well as the robustness that ARNI appears to be superior to ACE in PARADIGM-HF, the authors appropriately call for a large multicenter trial by the US/Canada -based Alliance for Adult Research in Congenital Cardiology (AARCC) to be performed on a prospective basis, as we have a multitude of ACHD patients suffering premature death due to systolic ventricular dysfunction despite good repairs as children, thus more evidence that ARNI can alleviate that burden will be very helpful.    

Familial clustering of bicuspid aortic valve and its relationship with aortic dilation in first-degree relatives. Galian-Gay L, Carro Hevia A, Teixido-Turà G, Rodríguez Palomares J, Gutiérrez-Moreno L, Maldonado G, Gonzàlez-Alujas MT, Sao-Aviles A, Gallego P, Calvo-Iglesias F, Bermejo J, Robledo-Carmona J, Sánchez V, Saura D, Sevilla T, Burillo-Sanz S, Guala A, Garcia-Dorado D, Evangelista A; BICUSPID investigators. Heart. 2019 Apr;105(8):603-608. doi: 10.1136/heartjnl-2018-313802. Epub 2018 Oct 15. PMID: 30322846 Take Home Points: In this cross-sectional, multi-center, Spanish study, bicuspid aortic valve is present in about 6.4% of first degree relatives of bicuspid aortic valve patients and an affected member was identified in 14.8% of families. The subtype of valve morphology did not follow a heritable pattern. Of first degree relatives with trileaflet aortic valve, almost 10% had aortic dilation that was usually mild and more frequently associated with hypertension. In a subset of patients with aortic dilation and trileaflet aortic valve who had CT angiography, 41% were actually found to have subtle bicuspid valve features with mini-raphe that were not obvious by echo. Commentary from Dr. Maan Jokhadar (Atlanta), section editor of ACHD Journal Watch:  In patients with bicuspid aortic valve (BAV), screening of first degree relative (FDR) for BAV is recommended by society guidelines. This is due to the observation of BAV familial clustering, which likely has polygenic inheritance with incomplete penetrance and variable expression. Less known are the inheritance patterns of BAV morphological types or aortic dilation without bicuspid valve in FDR of BAV patients. Dr. Galian–Gay and colleagues performed a cross-sectional multi-center study and screened FDR of BAV probands who agreed to undergo echo screening to establish BAV prevalence, aortic dilation prevalence, and describe BAV morphologic type inheritance pattern in FDR of BAV patients. Between 2012 and 2015, 852 BAV patients were identified prospectively from 8 Spanish tertiary referral centers and 256 agreed to undergo family screening.  Transthoracic echocardiography was performed on each index case and FDR participant as well as 3 generation pedigree. Out of the 1253 FDR candidates, only 724 participated. The remaining FDR were either not available (292; 23.3%) or had died (237; 18.9%). The mean FDR age was 41.7 years and nearly half were males and 6.4% were found to have BAV. A new affected family member was identified in nearly 15% of families. FDR with BAV were more frequently men at 71.7% and more often hypertensive. BAV was classified by morphologic subtype (fusion of the right-left cusps 73.9%, right-non cusps 23.9%, and left-non cusps 2.2%).  No significant relationship was found among probands and relatives according to BAV morphotype. The degree of valve dysfunction was described and aortas were considered to be dilated if they were 1.96 standard deviations above the predicted diameter for particular patient. About 48% of FDR with BAV had aortic dilation compared with about 10% of FDR who had trileaflet aortic valve (TAV). Of interest, tubular ascending aorta dilation was more frequent in FDR with BAV 43.5% compared with 7.5% of FDR with TAV.  Conversely, aortic root dilation was comparable in both FDR groups (4.3% with BAV and 2.1% in TAV). Aortic dilation ≥45 mm was present in 6.5% of FDR with BAV compared with 0.4% of FDR with TAV. When a cutoff of greater than 50 mm was used, 6% of FDR with BAV and 0% of FDR with TAV. Notably, nearly 10% of FDR with TAV had aortic dilation, but these patients were older, more likely to be hypertensive, or have aortic regurgitation when compared to those without aortic dilation.  One subset of FDR with TAV and aortic dilation had CT angiography and 9 out 22 (41%) were actually found to have BAV with subtle cusp fusion/mini-raphe that were not seen with echo. In this cross-sectional, multi-centered, Spanish study, the prevalence of BAV in FDR was 6.4% and a new affected member identified in 14.8% of families.  The subtype of valve morphology did not follow a heritable pattern.  Of FDR with TAV, almost 10% at aortic dilation that was usually mild and more frequently associated with hypertension.  In a subset of patients with aortic dilation and TAV who had CT angiography, 41% were actually found to have subtle bicuspid valve that was not as obvious by echo. The findings of the study suggest that the familial clustering of BAV is not completely determined by genetic factors.  These findings also suggest that BAV morphology may be less determined by genetic factors and more likely related to epi genetic and/or environmental factors.  Ascending aorta dilation is common in BAV and often occurs in the absence of significant valve dysfunction, which bolsters the genetic/aortopathy theory, though hemodynamic causes for aortic dilation are probably also contributory. This was a well-designed study but notable limitations include the potential selection bias of patients seen and tertiary referral centers as well as only 30% possible candidates agreeing to participate in the study.  The findings of this study probably support the recommendation to screen first-degree relatives of bicuspid aortic valve patients for bicuspid aortic valve and/or aortic dilation.  

CMR feature tracking left ventricular strain-rate predicts ventricular tachyarrhythmia, but not deterioration of ventricular function in patients with repaired tetralogy of Fallot. Hagdorn QAJ, Vos JDL, Beurskens NEG, Gorter TM, Meyer SL, van Melle JP, Berger RMF, Willems TP. Int J Cardiol. 2019 Aug 1. pii: S0167-5273(19)30911-8. doi: 10.1016/j.ijcard.2019.07.097. [Epub ahead of print] PMID: 31402156 Free Article Similar articles Select item 31161492  Take Home Points: CMR-feature tracking derived measures of myocardial deformation are valuable for the prediction of VT or deterioration of ventricular function in patients with repaired TOF. LV systolic and diastolic circumferential strain-rate are identified as strong predictors of VT, of which LV systolic circumferential strain-rate was an independent predictor. No association between strain and strain-rate parameters and deterioration of ventricular function.   Commentary from Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch:   TOF is one of the most common CHD, with excellent survival into adulthood when surgical repair is performed early in childhood. However, progressive RV dysfunction, due to residual pulmonary incompetence, and LV dysfunction are believed to from a substrate for electrical instability, resulting in both atrial and ventricular tachyarrhythmias. Ventricular strain is a measure of relative deformation in a certain direction, with the unit percentage. In contrast, strain-rate measures the rate of this deformation, and therefore provides conceptually different information regarding myocardial performance. Furthermore, strain rate can be measured during both contraction phase and relaxation phase, providing information on systolic and diastolic function. The predictive value of CMR derived strain-rate parameters has not been reported previously in patients with repaired TOF. Thus, it remains unknown whether the conceptual differences between strain and strain-rate translate into different prognostic potential. The aim of this study was to investigate the value of both CMR-feature tracking derived strain and strain-rate as predictors for VT, and additionally as a predictor for deterioration of ventricular function on CMR in patients with repaired TOF. Patients with repaired TOF who underwent CMR investigation were included. Strain and strain-rate of both ventricles were assessed using CMR feature tracking. The primary outcome was a composite of the occurrence of sustained VT or non-sustained VT requiring invasive therapy. The secondary outcome was analyzed in patients that underwent a second CMR after 1.5 to 3.5 years. Deterioration was defined as reduction (≥10%) in right ventricular (RV) ejection fraction, reduction (≥10%) in left ventricular (LV) ejection fraction or increase (≥30mL/m2) in indexed RV end-diastolic volume compared to baseline. In total, 172 patients were included in this study, with a median age at the time of CMR examination of 24.3 years (interquartile range (IQR)15.9–35.4). Due to significant artifacts, 11 patients were excluded. Of the included patients, 54 patients (31%) were pediatric (>18 years). Mass and volume measurements could be performed in 169 patients(98%), pulmonary flow measurements could be performed in 166 patients (97%), and strain measurements could be performed in 166 patients (97%). Within the predefined timeframe, a baseline echocardiographic examination was available for 143 patients (83%), and a baseline ECG examination was available for 162 patients (94%).   Primary endpoint: Ventricular tachyarrhythmias 9 patients (4.5%) experienced the primary outcome. Univariate Cox-regression analysis showed no significant associations between RV-strain variables and primary outcome. However, a significant association of both systolic and diastolic LV circumferential strain-rate with primary outcome was demonstrated. Secondary endpoint: ventricular deterioration 70 patients were included for secondary endpoint analysis. Of these, 14 patients were classified as deteriorated and 56 as not deteriorated. At baseline, RV EDVi and RV mass index were significantly different between the deteriorated and not-deteriorated group (145.7 ± 29.3 vs. 121.1 ± 32.4 mL/m2, p = 0.012 and 47.0 ± 8.1 vs.41.5 ± 9.3 g/m2, p = 0.048 respectively). Using logistic regression, only RV EDVi at baseline appeared significantly associated with deterioration (p = 0.018, odds ratio 1.26, 95% CI 1.04–1.51 per 10 mL/m2 increase) whereas for RV mass index, there was a borderline significant association (p=0.055, odds ratio 1.37, 95% CI 1.00–1.88 per 5 g/m2 increase). None of the strain or strain-rate variables were associated with deterioration. Conclusion: The present study shows that systolic LV circumferential strain-rate is a strong predictor for the primary endpoint of VT, independent of conventional variables in a population of both children and adults with repaired TOF. Furthermore, RV EDVi was associated with deterioration of ventricular function. On the contrary, no association could be demonstrated between strain and strain-rate parameters and deterioration of ventricular function. As surveillance for potentially life-threatening arrhythmias and ventricular deterioration is key in the long-term clinical follow-up of repaired TOF, the current study suggests that strain-rate parameters may improve risk stratification in these patients.

Results of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial. Goldberg DJ, Zak V, Goldstein BH, Schumacher KR, Rhodes J, Penny DJ, Petit CJ, Ginde S, Menon SC, Kim SH, Kim GB, Nowlen TT, DiMaria MV, Frischhertz BP, Wagner JB, McHugh KE, McCrindle BW, Shillingford AJ, Sabati AA, Yetman AT, John AS, Richmond ME, Files MD, Payne RM, Mackie AS, Davis CK, Shahanavaz S, Hill KD, Garg R, Jacobs JP, Hamstra MS, Woyciechowski S, Rathge KA, McBride MG, Frommelt PC, Russell MW, Urbina EM, Yeager JL, Pemberton VL, Stylianou MP, Pearson GD, Paridon SM; Pediatric Heart Network Investigators. Circulation. 2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044352. [Epub ahead of print] PMID: 31736357 Similar articles Select item 31736331 Take Home Points: Six months treatment with long-acting PDE5-inhibitor Udenafilresulted in a small but non-significant increase in peak VO2 (primary outcome) in adolescents with single ventricle congenital heart disease and Fontan circulation Small significant improvements of uncertain clinical significance were seen in a range of secondary outcome measures of submaximal exercise at the ventilatory anaerobic threshold Albeit an essentially negative study, this is an excellent large, prospective, double-blind, randomized, multi-centre, placebo-controlled study which offers invaluable information for clinicians treating people with Fontan circulation.  Commentary from Dr. Timothy Roberts (Melbourne), section editor of ACHD Journal Watch: Background In the Fontan circulation, pulmonary blood flow is dependent on low pulmonary vascular resistance to maintain sufficient single ventricle preload. Adolescents have reduced exercise capacity relative to healthy peers, and this difference is accentuated over time and associated with an increased rate of hospitalization and heart failure symptoms. Previous studies evaluating pulmonary vasodilator therapy have reported mixed results. The aim of the Fontan Udenafil Exercise Longitudinal (FUEL) study was to evaluate the effect of long-acting PDE5-inhibitor udenafil on exercise performance and a range of cardiovascular and functional outcomes in adolescents with Fontan circulation over a six-month period. Methods Patients aged between 12 and 18 years who had undergone Fontan palliation and were not prescribed a PDE5-inhibitor were eligible for enrollment. Exclusion criteria comprised severe ventricular dysfunction, severe atrioventricular valve regurgitation, and a previous VO2peak less than 50 % predicted. Enrolled participants were randomized in a 1:1 fashion to udenafil or placebo in a double-blind manner. Baseline investigations included measurement of brain-type natriuretic peptide (BNP), cardiopulmonary exercise testing (CPET), echocardiography, and assessment of peripheral vascular function using peripheral arterial tonometry (PAT). Maximal effort in the CPET (defined by respiratory exchange ratio > 1.1) was required prior to randomization and commencement of drug therapy. The primary outcome was the between group change in oxygen consumption at peak exercise (VO2). Secondary exercise outcomes included additional between group changes at maximal exertion and submaximal exercise (ventilatory anaerobic threshold). Secondary clinical outcomes were the between group differences in change in the echocardiographic-derived myocardial performance index (MPI), change in the PAT-derived measure of peripheral vascular function log-transformed reactive hyperemia index (lnRHI), and change in log-transformed serum BNP level. The study was powered correctly using historical data for CPET outcomes and used appropriate statistical techniques for analysis. Results Patient demographics are summarized in table 1 (below). A total of 400 subjects were recruited, with male predominance and mean age 15.5 years.   Resting, submaximal and peak exercise data are summarized in table 2 (below): Peak VO2 at maximal exertion increased 44 ml/min (2.8 %) in the udenafil group as compared to a marginal decline in the placebo cohort (-3.7 ml/min, -0.2 %) which did not reach statistical significance (P=0.071). VO2 was able to be calculated at anaerobic threshold in 317 subjects; in this subset there was a statistically significant increase in VO2 in the udenafil group (33 ml/min, 3.2 %) as compared to a reduction of 9 ml/min (-0.9 %) in the placebo group (P=0.012). Ventilatory efficiency (VE/VCO2) improved marginally while work rate also improved in the udenafil group (+3.8 METS vs. +0.34 METS; P=0.021). There were no significant changes in secondary clinical endpoints. Discussion While the small increase in peak exercise VO2 failed to reach statistical significance, the authorship group contend that peak VO2 may not be as relevant an endpoint in the Fontan circulation and rather outcomes at submaximal exertion may be more sensitive to pharmacologic manipulation of the pulmonary vasculature. It is difficult to quantify the clinical relevance of the small improvements in submaximal exercise performance measurements, however this outstanding research may lead to further research opportunities assessing PDE5-inhibition and submaximal exercise performance within subpopulations of Fontan circulation patients.  

Long-term clinical outcomes of valsartan in patients with a systemic right ventricle: Follow-up of a multicenter randomized controlled trial. van Dissel AC, Winter MM, van der Bom T, Vliegen HW, van Dijk APJ, Pieper PG, Sieswerda GT, Roos-Hesselink JW, Zwinderman AH, Mulder BJM, Bouma BJ. Int J Cardiol. 2019 Mar 1;278:84-87. doi: 10.1016/j.ijcard.2018.11.027. Epub 2018 Nov 10. PMID: 30449692 Similar articles Select item 30414749 Take Home Points: Systemic RV failure remains a leading cause for mortality in patients with transposition of the great arteries and an atrial switch or ccTGA. Valsartan therapy, in the long term (8 year follow-up) did not demonstrate an overall clinical or survival benefit. It was associated however with a reduction in morbidity in symptomatic patients.   Commentary by Dr. Blanche Cupido (Cape Town), section editor of ACHD Journal Watch:  Failure of the systemic right ventricle remains a major source of morbidity and mortality in patients with an atrial switch correction for complete transposition of the great arteries (TGA) or in congenitally corrected transposition of the great arteries (ccTGA). There is limited data on the use of renin-angiotensin-aldosterone-system (RAAS) inhibition in this group of patients. In the VAL-SERVE trial (Valsartan in the Systemic Right Ventricle), there was no significant overall effect of valsartan on RV function at 3 years – in symptomatic patients, however, there was a signal to positive remodeling. Given that in a similar study of LV function and Enalapril, benefit in asymptomatic patients was only evident after >10 years, this study aimed to assess the longer term  (8 year) clinical outcomes of patients from the VAL-SERVE cohort. 88 Patients from 6 Dutch university medical centers (CONCOR Registry) with TGA-atrial switch and ccTGA were enrolled into the VAL-SERVE trial between 2006 and 2009. This was a double blind, randomized control placebo study. Patients were assigned 1:1 to either placebo or control groups (44 valsartan, 44 placebo) and followed up for 3 years. The events recorded included supraventricular arrhythmias, worsening heart failure, tricuspid valve surgery and death. NYHA I was deemed asymptomatic. Both the valsartan and placebo groups had similar clinical characteristics at baseline. The average age at enrollment was 33 years and one third was symptomatic in each group. By the end of the 3 year trial, 17 patients continued valsartan (10 from valsartan group and 7 from placebo group); 11 (from both groups) patients switched to ARB’s / ACE-I. There was no difference in the proportions of the patients taking RAAS inhibitors during the extended 8.3 year follow-up. Mortality was similar for the randomized groups (3 deaths in each). Twenty-three patients in the treatment (valsartan) group (52%) and 30 in the placebo group (60%) had a primary clinical event. There was a non-significant reduction in the Valsartan treatment group for the combined primary endpoint of mortality and events (HR 0.65 95% CI 0.38-1.12). For the individual clinical endpoints, there was no difference between the Valsartan and the placebo groups: Supraventricular arrhythmias (41% vs 50%) Ventricular arrhythmias (27% vs 27%) Worsening heart failure (23% vs 23%) Tricuspid valve surgery (6% vs 6%)   In a third of patients, more than one event was recorded. Overall, Valsartan did not improve survival of the cohort but survival rate was noted to be lower in those patients who were symptomatic at the time of presentation (81% vs 98%, p=0,010).   Valsartan reduced the risk of events in the symptomatic group (HR 0.37 95%CI 0.17-0.92) but not in the asymptomatic patients (HR 0.84 95%CI 0.42-1.69). There was however no significant treatment benefit among symptomatic compared to asymptomatic patients (p=0.146 for interaction)

Outcome of the Glenn procedure as definitive palliation in single ventricle patients. Vermaut A, De Meester P, Troost E, Roggen L, Goossens E, Moons P, Rega F, Meyns B, Gewillig M, Budts W, Van De Bruaene A. Int J Cardiol. 2019 Nov 18. pii: S0167-5273(19)34712-6. doi: 10.1016/j.ijcard.2019.10.031. [Epub ahead of print] PMID: 31761401 Similar articles Select item 31812566 Take Home Points: A single center retrospective review described the outcomes in a heterogenous group of patients with complex congenital heart disease undergoing SV-Glenn shunt as definitive therapy In the SV-Glenn group, there is significant peri-operative / early mortality (within 6 months): (±7% of all TCPC completions) – mainly attributed to HLHS Of the 25 SV-Glenn survivors, 8 had contra-indications to TCPC completion. In this group, only 1 survived to adulthood. In selected adults, SV-Glenn shunt is possible with reasonable medium and long term outcomes. Co-morbidities like heart failure, arrythmias, stroke and endocarditis are frequently encountered. This is a retrospective review, and selection bias in particular needs to be borne in mind when interpreting these results   Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch:  The Glenn Shunt is a palliative surgery involving an end-to-end anastomosis between the superior caval vein and the pulmonary arteries. It is usually the intermediary step toward Fontan circulation or TCPC (total cavo-pulmonary connection) completion but is, at times, encountered in Adult Congenital Heart Disease Practice as a definitive procedure in select patients with either single ventricle physiology (SV-Glenn) or biventricular physiology (one-and-a-half-repair – OAHR).   This is a single center study at a tertiary referral unit in Belgium (Leuven Hospital) that aimed to describe the characteristics of the SV-Glenn population, their clinical features prior to definitive palliation and their long-term outcomes in term of morbidity and mortality. All patients from the local paediatric and adult database who underwent a Glenn palliation before May 2018 were included. Original anatomical data, clinical – and demographic data, imaging and haemodynamic data were recorded. The peri-operative complications (bleeding, thrombotic complications, need for re-intervention/ take-down, occurrence of heart failure) were noted. Early (within 6 months of Glenn-SV palliation) and late (>6 month) mortality were recorded. At the last follow-up, clinical data and outcome data pertaining to heart failure, effort tolerance (NYHA class), arrythmias, thrombotic events, infective endocarditis, need for pacing, presence of cirrhosis and protein-losing enteropathy were documented.   In total, 65 patients underwent a Glenn procedure without a TCPC completion. Of these, 21 had a Glenn with biventricular circulation (excluded), leaving 44 with a univentricular circulation Glenn (SV-Glenn). A bidirectional Glenn was performed in 43 patients with a classic Glenn procedure in one patient. The median age at Glenn procedure with 11.9 months. Forty-three percent (n=19) died within 6 months after the Glenn shunt. Seven of these patients had hypoplastic left heart syndrome. The cause of death was cardiac in 15 patients (11 had cardiogenic shock, 4 had peri-operative bleeding or thrombotic events), in 3 patients the cause was unknown and in one case it was non-cardiac. A total of 25 patients with a SV-Glenn shunt survived beyond 6 months. In this group, the median age at time of Glenn was 6.3 years. Eight patients were aimed for TCPC but had contraindications to TCPC completion (3 had small pulmonary arteries, 2 had severe ventricular dysfunction, 1 had significant co-morbidity, 1 had sudden cardiac death). For the other 17, TCPC was not thought to be of potential benefit. Cardiac cath data was available in 19 patients prior to Glenn procedure. The median mean PA pressure was 16mmHg, wedge pressure 9mmHg and aortic saturation 86%. Post Glenn procedure, median mean PA pressure was 19mmHg, wedge pressure 16mmHg, and aortic saturation 85%. Median follow-up of this cohort was 11 years. Five late deaths (see figure 2 above) occurred in the SV-Glenn group (2 were due to heart failure, 1 sudden cardiac death, 1 due to hemoptysis, 1 unknown). Three deaths occurred in patients unsuitable for a TCPC (38% mortality over a median follow-up of 4.5 years). In the rest of the cohort, the Glenn shunt improved saturation, offloaded the systemic ventricle – but without a planned TCPC, the mortality was 12% over a median follow-up of 27 years. Eight patients underwent SV-Glenn during adulthood (ages ranged from 25-59 years) due to progressive desaturation resulting in functional impairment. The median mean PA pressure was 17mmHg and the wedge mean 12mmHG. One patient died in the perioperative period and in the remaining patients, all but one showed symptomatic improvement, both in terms of saturation and functional capacity.    

Non-vitamin K antagonist oral anticoagulants in adults with a Fontan circulation: are they safe? Yang H, Veldtman GR, Bouma BJ, Budts W, Niwa K, Meijboom F, Scognamiglio G, Egbe AC, Schwerzmann M, Broberg C, Morissens M, Buber J, Tsai S, Polyzois I, Post MC, Greutmann M, Van Dijk A, Mulder BJ, Aboulhosn J. Open Heart. 2019 Jun 3;6(1):e000985. doi: 10.1136/openhrt-2018-000985. eCollection 2019 PMID: 31245011 Free PMC Article Similar articles Select item 31158256 Take Home Points: The 2014 PACES/HRS gave NOACS a class III recommendation for use in Fontan patients with atrial arrhythmias – this was based on a lack of data rather than reported adverse events. This is the first study providing prospective safety data for the use of NOACS in Fontan patients. They showed comparable safety and efficacy to VKA’s with an annual rate of 2.9% respectively for thromboembolism and major bleeding. Since the mean follow-up in this study was only 1.4 years, longer follow-up data is needed.   Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch:  Patients with Fontan circuits are at risk of both thromboembolism and bleeding. Previous recommendations included the use of aspirin or Vitamin K antagonists. The data supporting its use is scanty and derived largely form observational studies. Furthermore, both poor INR control with limited time in therapeutic range as well as aspirin resistance, reduced the efficacies of both these treatment strategies. In the treatment of non-valvular AF, Non- vitamin K antagonist oral anticoagulants (NOACS) have been shown to be as efficacious as vitamin K antagonists (VKA’s) in reducing thromboembolic events with fewer intracranial bleeds and drug interactions as well as obliterating the need for INR monitoring.  In Fontan patients with atrial arrythmias, NOACS currently have a class III recommendation by the PACES/HRS 2014 guideline. This recommendation was based on the lack of adequate available data and not on a documented safety hazard. Therefore, despite this recommendation, NOACS have been used increasingly in this population. This study focused on the safety and efficacy of NOAC use in Fontan patients with prior atrial arrhythmia. Patients enrolled in the NOTE registry (NOACS for thromboembolic prevention in patients with CHD). The NOTE registry is a worldwide ongoing prospective registry in ACHD patients on NOACS for the prevention of thromboembolism.  Recruitment commenced in April 2014 (35 centers in 10 countries including Europe, North America, the Middle East and east Asia). Consecutive patients with Fontan circulation were identified. Patients were followed up at 6 months, 1 year and 2 years. Primary endpoints were thromboembolism (ischemic CVA, TIA, systemic or pulmonary embolism, intra-cardiac embolism) and major bleeding (defined as bleeding requiring hospitalizations / interventions/the transfusion of 2 or more units of packed cells or a haemoglobin drop > 20 g/L and/or fatal bleeding or bleeding occurring in one of the following critical sites: intracranial, intraspinal, intraocular, pericardial, intra-articular or intra-muscular with compartment syndrome. Minor bleeding was a secondary endpoint. A total of 74 Fontan patients were identified from a total of 513 ACHD patients on NOACS. The indications for NOACS were atrial arrhythmias (n=52), primary prevention (n=12) and secondary prevention (n=10). The CHA2DS2VASc score was >1 in 66% (n=49) and only 2 patients had high HAS-BLED scores. During the mean follow-up of 1.4 years (102.4 patient years), 3 thromboembolic events (pulmonary emboli, 1 ischemic cerebrovascular event –) and 3 major bleeds (2 menorrhagia, 1 major GIT bleed)occurred in 5 patients with AP Fontans and one patient with TCPC - annual rate 2,9%, 95% CI 0.7-7.6%, respectively.  Minor bleeding occurred in 15 patients (annual rate 15.8%, 95% CI 9.1-25.2%). Figure 1A below shows the Kaplan-Meier curves of survival free from thromboembolism, major bleeding and minor bleeding. Two patients died during follow-up – 1 heart failure and 1 cancer death. Prior to NOAC initiation, 50% (n=37) were on VKA’s, 26% (n=19) were taking aspirin and 24% (n=18) had no antithrombotic treatment. In the subgroup who started NOACS de-novo for primary prevention (i.e. no prior VKA or aspirin use), no thromboembolic events of major bleeding occurred. Figure 1B above depicts the event free survival of those patients on VKA’s in the 3 years prior to changing to NOACS. In this group, over a 3.5year period, the annual event rate was 6.2% for thromboembolism (95% CI 1.9% to 14.4%) and 0% for major bleeding. A total of 14 patients stopped NOAC therapy to recommence VKA’s. Reasons included: thromboembolism (n=3), bleeding (n=4), side-effects (n=2), pregnancy (n=2), patient refusal (n=2), Fontan conversion (n=1).   .

Maternal and fetal outcomes in pregnancies complicated by Marfan syndrome. Cauldwell M, Steer PJ, Curtis SL, Mohan A, Dockree S, Mackillop L, Parry HM, Oliver J, Sterrenberg M, Wallace S, Malin G, Partridge G, Freeman LJ, Bolger AP, Siddiqui F, Wilson D, Simpson M, Walker N, Hodson K, Thomas K, Bredaki F, Mercaldi R, Walker F, Johnson MR. Heart. 2019 May 25. pii: heartjnl-2019-314817. doi: 10.1136/heartjnl-2019-314817. [Epub ahead of print] PMID: 31129614 Similar articles Select item 31126344 Take Home Points: No deaths occurred in this cohort of 258 pregnancies in 151 Marfan patients The aortic dissection rate was 1.9%  (mainly type B) No specific clinical or imaging predictors of dissection were identified A significant but small increase in aortic root diameters was noted following pregnancy Neonates of those on betablocker therapy had lower birth weights The elective Caesarian section rate was higher in patients with dilated aortic roots Post-partum haemorrhage complicated 40% of deliveries (double that of the general population).   Commentary by Dr. Blanche Cupido (Cape Town), section editor of ACHD Journal Watch:  Marfan syndrome is associated with an increase in cardiovascular mortality, especially relating to aortic dissection. Pregnancy is thought to increase the risk of aortic dissection but previous studies were small and variable in its descriptions of specific complications. There is no good data to show that betablocker use reduces the risk of aortic dissection in pregnancy. This retrospective observational study was conducted at 12 UK centers with the aim of gaining information to help direct counselling and management of Marfan Syndrome in pregnancy. Patients delivering between January 1998 and March 2018 were enrolled and data pertaining to maternal and neonatal outcomes recorded. The primary outcome was the occurrence of aortic dissection during pregnancy or up to 6 months post-partum. The secondary cardiac outcomes were cardiac surgery or stroke. Obstetric outcomes (gestational hypertension, pre-eclampsia, preterm delivery, postpartum haemorrhage and venous thromboembolism) and neonatal outcomes (small for gestational age, stillbirth and neonatal unit admission) were recorded. Two hundred and fifty-eight pregnancies occurred in 151 patients. These included 226 pregnancies >24 weeks gestation, 20 miscarriages and 12 terminations.  There were 213 live births. Thirty-five pregnancies occurred in 21 women with previous ascending aorta replacements. Only 47.8% of women had preconception counseling in their first pregnancy. The median age at diagnosis was 14.5 years and the median age at pregnancy 29 years. Most patients (80%) had an aortic root diameter of <40mm on echo pre-conception. Five patients had an aortic dissection during pregnancy (1 type A, 4 type B). No specific predictors for aortic dissection were identified, but the sample size was small and moderate associations could therefore not be excluded. 6 Cardiac surgeries and 2 strokes occurred during the pregnancies and post-partum period.   After excluding women with prior aortic root replacements, echo data pre- and post-pregnancy was available in 58 women. The median aortic root size pre-pregnancy was 36mm and 37mm post pregnancy – a small but significant increase (p=0.01).  This change was not significantly modified by the use of betablockers. There was no correlation between aortic root size and the time of delivery. However, in patients with a maximum aortic root diameter of <40mm, the caesarian section rate was 26% compared to 70.4% in those with a root diameter > 40mm (p<0.001). Betablocker use was documented on 64.2% of pregnancies and was more likely to be prescribed in women with larger aortic roots. The median birth weight was significantly reduced in women on betablockers compared to those who were not taking it (3024 g vs 3310 g, p=0.002). 40% of women experienced post-partum haemmorhage – this is double the rate of the general population.

Relation Between New York Heart Association Functional Class and Objective Measures of Cardiopulmonary Exercise in Adults With Congenital Heart Disease. Das BB, Young ML, Niu J, Mendoza LE, Chan KC, Roth T. Am J Cardiol. 2019 Jun 1;123(11):1868-1873. doi: 10.1016/j.amjcard.2019.02.053. Epub 2019 Mar 15. PMID: 30954207 Similar articles Select item 30919579   Take Home Points: NYHA class of patients is a simple measure for assessment of functional status, CPET remains an important tool to identify the source of exercise limitation in ACHD patients. CPET can provide objective and reproducible assessment of the cardiovascular, respiratory, and muscular systems. 3 of CPET parameters (pVO2, OUES, and maximum DP) overall correlate well with NYHA functional class especially between NYHA functional class I and III. If CPET cannot be performed, stratification using NYHA class is an acceptable alternative. Commentary from Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch:  Das et al compared the New York Heart Association (NYHA) functional class in adults with CHD patients with measured cardiopulmonary exercise testing parameters. This was a retrospective study which included 175 ACHD patients who underwent CPET between 2014 till 2018 in a single center. The majority of patients were repaired TOF (26%) followed by Fontan patients (19%) and repaired TGA with arterial or atrial switch (16%). The NYHA class was determined for each patient by physician assessment of patients’ self-reported symptoms before the exercise test or estimated from patient narrative from the medical record. Only patients with NYHA class I to III were enrolled in the study, as they were able to participate in CPET. Symptoms limited CPET was performed on all patients using treadmill according to modified Bruce protocol (97% of patients) or cycle ergometer ramping protocol (3% of patients). The measured parameters were: Peak VO2 max, as the highest 30-second average during exercise.VO2 value was adjusted per ideal body weightthe normal was > 20 ml/kg/min. The VE/VCO2 nadir was taken as the lowest 30-second average duringexercise, the cutoff of 34 (a prognostic tool of heart failure). O2 uptake efficient slob (OUES) was measured as relationship between VO2 max and Log VE thought the exercise., cutoff value was 2,000. Double product (DP) is the myocardial O2 uptake, defined as the amount of O@ consumed by the myocardium during exercise, was estimated by the product of heart rate and systolic blood pressure, cut off value was 20.000. Results: Peak VO2in the overall study population was 26.4 ± 9.8 ml/kg/min or 72.7 ± 22.3% of predicted. There was a progressive decline in pVO2 with increasing severity of CHD (p = 0.001).   There was a strong negative correlation between functional class and pVO2, with a progressive decline from functional Class I to III (r = ¡0.48; p 0.0001). About ¼  of patients had pVO2 <20ml/kg/min and there was an overlap in pVO2 in each NYHA functional class.   However, 75% of NYHA class III had pVO2 <20 ml/kg/min compared with 10% in NYHA class I. Patients in functional class III had a markedly reduced pVO2 of 16.8 ± 4.5ml/kg/ min compared with 26.6 ± 6.1 ml/kg/min in class I (p = 0.0002).There was no significant difference in pVO2 between NYHA class II and III (p = 0.09), whereas the difference between NYHA class I and II and Class I and III are significant (p <0.004 and p <0.00002 respectively. Figure 1. Relation between Peak VO2 and NYHA class. (A) Spearman correlation between pVO2 and NYHA class, (B) frequency of distribution of pVO2, (C) Relative distribution with a cut-off value of pVO2 20 ml/kg/min, and (D) Box and whisker-plot demonstrating median and quartiles of pVO2 by NYHA class. NYHA = New York Heart Association.   The VE/VCO2 slope in the overall study population was 31.7 ± 5.4. Patients in functional class III had the higher VE/VCO2 slopes compared with class I and II, but there was no significant correlation between NYHA class and VE/VCO2 slope (r = 0.14, p = 0.37).   The distribution of VE/VCO2 slope was within upper normal limits in functional class I patients, but one-fifth of these asymptomatic patients (20%) had an abnormal slope > 34. Almost one half of patients in NYHA class II (42%) and III (50%) had a VE/VCO2 slope > 34.There was no significant difference between NYHA class I and II (p = 0.071), or between Class II and III (p = 0.263), whereas VE/VCO2 was significantly different between Class I and III (p = 0.011). Figure 2 Relation between VE/VCO2 slope and NYHA class. (A) Spearman correlation between VE/VCO2 and NYHA class, (B) frequency of distribution of VE/VCO2, (C) Relative distribution with a cut-off value of VE/VCO2 34, and (D) Box and whisker-plot demonstrating median and quartiles of VE/VCO2 by NYHA class. NYHA = New York Heart Association.   The VE/VCO2 slope in the overall study population was 31.7 ± 5.4. Patients in functional class III had the higher VE/VCO2 slopes compared with class I and II, but there was no significant correlation between NYHA class and VE/VCO2 slope (r = 0.14, p = 0.37).   The distribution of VE/VCO2 slope was within upper normal limits in functional class I patients, but one-fifth of these asymptomatic patients (20%) had an abnormal slope > 34. Almost one half of patients in NYHA class II (42%) and III (50%) had a VE/VCO2 slope > 34.There was no significant difference between NYHA class I and II (p = 0.071), or between Class II and III (p = 0.263), whereas VE/VCO2 was significantly different between Class I and III (p = 0.011).     Figure 2 Relation between VE/VCO2 slope and NYHA class. (A) Spearman correlation between VE/VCO2 and NYHA class, (B) frequency of distribution of VE/VCO2, (C) Relative distribution with a cut-off value of VE/VCO2 34, and (D) Box and whisker-plot demonstrating median and quartiles of VE/VCO2 by NYHA class. NYHA = New York Heart Association.     The OUES in the overall study population was 2,565 ± 825. There was a progressive decline in OUES with increasing severity of NYHA class (r = ¡0.35, p <0.0001). Majority of ACHD patients had OUES > 2000. There was no significant difference in OUES between NYHA class II and III (p = 0.158), whereas the difference between NYHA class I and II and Class I and III were significant (p < 0.001). Figure 3. Relation between OUES slope and NYHA class. (A) Spearman correlation between OUES and NYHA class, (B) frequency of distribution of OUES, (C) Relative distribution with a cut-off value of OUES 2,000, and (D) Box and whisker-plot demonstrating median and quartiles of OUES by NYHA class. NYHA = New York Heart Association; OUES = O2 uptake efficient slope. The maximum DPin the overall study population was 26,602 ± 6,127. There was a progressive decline in maximum DP with increasing NYHA functional class (r = ¡0.31, p <0.0001). Majority of patients had DP > 20,000.   There was no significant difference in maximum DP between NYHA class II and III (p = 0.749), whereas the difference between NYHA class I and II and Class I and III were significant (p <0.001 and p<0.05 respectively). Figure 4. Relation between maximum double product and NYHA class. (A) Spearman correlation between double product (DP) and NYHA class, (B) frequency of distribution of DP, (C) Relative distribution with a cut-off value of DP 20,000, and (D) Box and whisker-plot demonstrating median and quartiles of DP by NYHA class. NYHA = New York Heart Association; OUES = O2 uptake efficient slope. Conclusions: NYHA functional class correlates with objective measures of CPET, however there is wide variability in measured exercise capacity in each NYHA classification. Therefore, whereas NYHA class of patients is a simple measure for assessment of functional status, CPET is an important tool to identify the source of exercise limitation in ACHD patients.    

Progression of aortic root dilatation and aortic valve regurgitation after the arterial switch operation. van der Palen RLF, van der Bom T, Dekker A, Tsonaka R, van Geloven N, Kuipers IM, Konings TC, Rammeloo LAJ, Ten Harkel ADJ, Jongbloed MRM, Koolbergen DR, Mulder BJM, Hazekamp MG, Blom NA. Heart. 2019 Jul 10. pii: heartjnl-2019-315157. doi: 10.1136/heartjnl-2019-315157. [Epub ahead of print] PMID: 31292191 Free Article Similar articles Select item 31289972 Take Home Points: Neo-aortic root dilatation and aortic incompetence in patients post ASO is progressive – does not stabilize over time. More complex subtypes of TGA and male gender were associated with greater increases in root dilatation. A disproportionate increase of aortic root size occurs in the first year post ASO. Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch:  The arterial switch operation (ASO) has largely replaced the atrial switch procedure for transposition of the great arteries (TGA) over the last 2 decades. The late survival with this procedure has been excellent but the concern of neo-aortic dilatation (in >2/3 of patients) and aortic regurgitation (AR) remains. There is however limited data, especially in adults, on the progression of neo-aortic dilatation. This is a retrospective study from the Netherlands, describing neo-aortic growth, neo-aortic valve function and the need for neo-aortic root intervention at long term follow-up and to identify risk factors for root dilatation and AR.   All patients who underwent an ASO for TGA with intact ventricular septum (TGA-IVS), TGA with VSD (TGA-VSD) or double outlet RV with subpulmonary VSD (DORV-SP-VSD) between 1977 and 2015 were included. All patients had 2 or more echocardiograms during follow-up. If possible, echo images at 3,6,9 and 12 months and then at 2,3 and 5 years and 5 year intervals thereafter were evaluated until the last available follow-up. The following neo-aortic measurements were recorded: annulus, mid-sinus and sinotubular junction. For paediatric patients, Z scores were calculated and dilatation defined as a Z score of 2 or more. AR jet and LV dimensions were also assessed. A total of 452 patients underwent ASO. Fifty-two patients (11.5%) patients died during follow-up of which 42 deaths occurred during the first month post-op. Early deaths were higher in the years 1977-1987, and reduced to 3.3% in subsequent years. The cohort was made up of the following morphological subtypes: TGA-IVS (66.7%), TGA-VSD (25.8%) and DORV-SP-VSD (7.5%). Figure 2A-C above shows the absolute neo-aortic diameters for all patients with TGA. The dimensions for neo-aortic annulus, root and STJ shows a rapid increase in the first year post- ASO followed by a linear increase in childhood and an ongoing increased growth rate in adulthood. For neo-aortic annulus and root diameters, both TGA-VSD and DORV-PS-VSD showed significantly greater dilatation compared to TGA-IVS. Both morphological subtype and male gender were independent predictors for root dilatation. Regarding aortic regurgitation, at last follow-up or just before re-operation for root pathology, 33 patients (9.6%) had at least moderate AR.

Outcomes in adults with congenital heart disease and heterotaxy syndrome: A single-center experience. Broda CR, Salciccioli KB, Lopez KN, Ermis PR, Moodie DS, Dickerson HA. Congenit Heart Dis. 2019 Oct 16. doi: 10.1111/chd.12856. [Epub ahead of print] PMID: 31617655 Similar articles Select item 31578117 ake Home Points: First study to assess clinical outcomes in adult patients with heterotaxy syndrome and CHD. The risk for early death, transplantation and co-morbidities remains high. Median survival of 54% at age 40. No congenital anatomic factors (ventricular status or HS type) were associated with reduced survival. Heart failure portends a worse prognosis. Nearly all patients had developed tachyarrythmias by age 50. 20% of patients experienced cerebrovascular accidents at point of last follow-up. In patients born after January 1985, intervention, including Fontan completion occurred at an earlier age. Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch:   Heterotaxy syndrome is a condition characterized by the abnormal lateral arrangement of thoraco-abdominal organs, and frequently associated with complex congenital heart disease (CHD). Even in the contemporary era, morbidity and mortality remains high. Very little is known about this condition relating to CHD in adults with data currently being extrapolated from paediatric data. This is a single tertiary center (Texas, US) retrospective folder review of adult patients between 1968 and 2018. They aimed to describe the sociodemographics and clinical outcomes in adult patients with heterotaxy syndrome and congenital heart disease. Patients were excluded if they had situs inversus totalis, or without thoraco-abdominal laterality defect. The group was then subdivided based on splenic anatomy. A total of 62 patients met the inclusion criteria. Of the 62 patients included, 29% (n=18) had heterotaxy syndrome with polysplenia (HS-PS), 46.7% (n=29) had heterotaxy syndrome with asplenia (HS-AS). The remaining patients had insufficient data to define splenic anatomy. The median age of the cohort was 22.7 years and 41.9% were female.  Twelve (19.3%) were transplanted or dead – average age of this subgroup was 28.8 years. Three men had fathered children and one female with a Fontan circulation successfully carried a pregnancy to term. Thirty-six interventions occurred in 24 patients after age 18 – 16 were cardiac catheterization lab interventions (angioplasty or stenting, device or coil placement, pericardiocentesis, Fontan fenestration, electrophysiology procedures). Eighteen surgical procedures occurred – Epicardial pacing, pulmonary artery plication/augmentation, Maze procedure, AV valve preplacement, Fontan conversion and heart transplant. Forty-three patients had single ventricles of which 71% had Fontan palliations. Twelve deaths occurred in total, 10 were pre-transplant. The overall transplant-free survival was 98.1% at age 20, 83.5% at age 30 and 54.2% at age 40 years. (Figure 1 below). Of all parameters, onlysystemic outflow obstruction neared statistical significance as a predictor for poor outcome. Neither ventricular status, nor HS type predicted survival disadvantage. Heart failure was seen in 29.8% (n=17/57). Those with heart failure by age 18 were more likely to die or receive transplantation with time to outcome of 2.6 years. Heart failure survival was 80.8%,58.7% and 31.1% at 20, 30 and 40 years respectively. (See figure 2 below) By age 18, 46.2% had no arrythmia, 25% had experienced tachyarrythmias, 17.3% had bradyarrhythmia and 11.5% experienced both tachy-and bradyarrythmias. Bradycardia-free survival was 33% at age 40. (Figure 3 below).  Bradycardia was not associated with a transplant-free survival disadvantage compared to no arrythmia. Tachycardia proved a survival disadvantage with a HR 6.48 (95% CI 1.41-29.75, p=0.016). The median age of tachycardia-free survival was 54%, 29.2% and  19.5% at 20,30 and 40 years respectively (Figure 3).  Cerebrovascular accidents (CVA) occurred in 22.4% of patients (n=13), 7 occurring before the age of age 18. CVA was associated with transplant-free survival disadvantage (HR 7.97, 95% CI 1.93-32.99, p=0.004). CVA free survival was 84.3%, 54.2% and 40.6% at 20,30 and 40 years respectively (See Figure 4) Patients were stratified by ‘era’: Early era included those born before age January 1985, and the late era were those born after January 1985. Late era patients had earlier median age of Fontan completion (6.3 vs 15 years, p=0.002).  

Elevated non-invasive liver fibrosis markers and risk of liver carcinoma in adult patients after repair of tetralogy of Fallot. Yamamura K, Sakamoto I, Morihana E, Hirata Y, Nagata H, Yamasaki Y, Okumura Y, Kohashi K, Koto K, Tsutsui H, Ohga S. Int J Cardiol. 2019 Jul 15;287:121-126. doi: 10.1016/j.ijcard.2019.04.032. Epub 2019 Apr 11. PMID:  31006598 Take Home Points: Liver fibrosis increases the risk of cardiac operation with cardiopulmonary bypass especially if it is associated with thrombocytopenia and/or coagulopathy. Elevated liver fibrosis markers due to hepatic congestion is present not only in adult patients after Fontan procedure but also after TOF repair. However, RV dysfunction and liver congestion could be resolved by pulmonary valve replacement in rTOF Careful monitoring of the liver fibrosis markers and reoperation at an appropriate  time may be beneficial in improving the long-term outcomes in rTOF patients with elevated right atrial pressure. Commentary by Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch:  In Fontan patients, the elevated systemic venous pressure leads to hepatic congestion and hepatic fibrosis. Chronic RV dysfunction and hepatic congestion develops over time and may lead to liver fibrosis, and subsequent development of liver cirrhosis late after repair of TOF (rTOF). However, the incidence and severity remain unclear. This study aimed to elucidate the incidence and severity of liver fibrosis in patients with rTOF. 50 TOF patients with PR/PS, 50 age-matched patients after Fontan procedure, and 11 control subjects were enrolled. Patients who had other forms of liver diseases, such as viral hepatitis or alcoholic liver disease were excluded. In all patients, liver fibrosis markers (hyaluronic acid and type IV collagen), hemodynamic parameters obtained from CMR and cardiac catheterization, and abdominal ultrasonography and liver biopsy data were documented. Hyaluronic acid levels in patients with rTOF were significantly higher than controls, and were lower than those after Fontan palliations. Type IV-collagen levels in patients with rTOF were higher than controls, and tended to be lower than those after Fontan. Patients with rTOF showed abnormal hyaluronic acid levels more frequently than controls, and less frequently than those after Fontan.   In patients with rTOF, hyaluronic acid levels correlated positively with time after repair (r= 0.39, p =0.005) and type IV collagen levels correlated positively with RA pressure (r=0.42, p= 0.007). On the other hand, in patients after Fontan, liver fibrosis markers showed no significant correlation with time after surgery or RA pressure. Type IV-collagen levels in patients with rTOF with moderate or severe TR (n = 13) was higher than those with less than moderate TR (n = 37). Other than that, there was no difference in type IV-collagen or hyaluronic acid levels among patients with PR, PR + PS, and PS, between patients with and without moderate or severe TR or between patients with and without restrictive RV physiology. Patients with hepatic congestion on abdominal ultrasound had significantly higher type IV collagen, higher total bilirubin, lower total protein, lower platelet count and higher RV end-diastolic pressure than those without hepatic congestion (p b 0.05, respectively). 23 patients with rTOF underwent PVR and 13 of them received the assessment of fibrosis markers after PVR. Liver fibrosis markers did not show statistically significant decrease after PVR in this small number of subjects (hyaluronic acid: median, 32 to 28 ng/mL, p = 0.588; type IV collagen: median 145 to 124 ng/mL, p =0.105). However, 12 patients (92%) and 10 patients (77%) had normalization of the hyaluronic acid and type IV collagen levels after PVR. Elevated RA pressure and pulmonary regurgitant fraction had an association with elevated type IV collagen. Although the predictive value of serum markers for liver fibrosis is not completely validated with comprehensive imaging tests or liver biopsy in this population, this association indicates the fibrosis markers should reflect the degree of liver fibrosis due to elevated RA pressure. There are several limitations about this study: the study population is relatively small, especially in patients who underwent imaging tests and biopsy of the liver, cardiac catheter data in the controls and CMR data in the Fontan patients and controls were not available in the majority of subjects because of the retrospective data collection, and there was no data to investigate the relationship between elevated liver fibrosis markers and prognosis. A prospective study with a larger population is needed to determine the clinical impact of elevation of these fibrosis markers.  

Over 25 Years of Experience with the Ross Procedure in Children: A Single-Centre Experience. Martin E, Laurin C, Jacques F, Houde C, Cote JM, Chetaille P, Drolet C, Vaujois L, Kalavrouziotis D, Mohammadi S, Perron J. Ann Thorac Surg. 2019 Dec 24. pii: S0003-4975(19)31919-8. doi: 10.1016/j.athoracsur.2019.10.093. [Epub ahead of print] PMID: 31881194 Similar articles Select item 31874649 Take Home Points: This study boasts the longest and most complete dataset for people treated with a Ross procedure. Mortality in the early post-operative period is low. Paediatric Ross survival has good long term survival: 96.7% at 5 years and 94.4% at 25 years. Ross related re-interventions was twice as common for the pulmonary homograft than for the autograft. Freedom from autograft-related intervention was 98.1% at 5 years and 61.2% at 25 years. Freedom from pulmonary conduit re-intervention was 93.2% at 5 years and 28.3% at 25 years. Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch:  In children, all available surgical options for aortic valve prostheses pose limitations. Both surgical repair techniques and balloon valvuloplasty are utilized to postpone valve replacement when possible. Though the Ross procedure is technically rather complex, it is a valuable and good option as aortic valve replacement in children. Re-intervention of the autograft and the pulmonary conduit have frequently been described and may impact longevity. This single center study described the long term clinical and echocardiographic outcomes following the Ross procedure in children at a tertiary referral center in Canada. It is a retrospective review of consecutive children (under age 18) who underwent a Ross procedure between January 1990 and January 2018 – a total of 25 years’ experience with this procedure. Clinical, surgical and echocardiographic data was reviewed. The primary outcome was in-hospital and long term survival. Long term valve-related outcomes and Ross-related interventions were also reviewed. Fifty-two percent of patients were followed up for > 20 years. Clinical data spanned 1019 person-years and echocardiographic data 977 person-years. Patients post-Ross procedure were followed up annually. A total of 63 patients underwent the Ross procedure. (81% of this cohort was male). Fifty-four percent (n=34) of patients, had one or more open surgical procedure prior to the Ross procedure.  51% had previous surgical aortic valvuloplasty and 22% had previous percutaneous balloon valvuloplasty. On average, the Ross procedure happened 4.6 years after these procedures. Isolated aortic stenosis was the pathology in 46% of patients. In 10% of patients, the surgery was urgent, it was semi-elective in 31% and elective in 59%. One patient died in the peri-operative period (1.6%). 6% of patients (n=4) required re-exploration for mediastinal bleeding. None required ECMO support. None developed in-hospital pulmonary autograft or homograft failure. Table 3 below shows the immediate post-operative outcomes: Two non-Ross related cardiac deaths occurred at 3.5 and 10.4 years post-Ross procedure respectively. Figure 1 below shows an overall survival of 98.4%, 94.4% and 94.4% at 1, 15 and 25 years respectively. Pulmonary autograft degeneration occurred in 19 patients (30%). None developed pulmonary stenosis. Fifteen of these patients had an autograft re-operation at a median of 15.9 years post-Ross procedure. Ten of these 15 patients, underwent autograft root-sparing procedure (David procedure). The other 5 had a Bentall procedure. No mortality was associated with re-operation.  Freedom from pulmonary autograft reoperation was 100% at 1 year, 86.4% at 15 years and 61.2% at 25 years (see figure 2 below): Forty-nine (n=31) percent of patients developed degeneration of the pulmonary homograft with 23 patients undergoing re-intervention at a median of 11.1 years. Thirteen patients had pulmonary stenosis, 10 had pulmonary incompetence and 8 had a combination of the above lesions. Freedom from any homograft re-intervention was 96.7 % at 1 year, 58.2% at 15 years and 28.3% at 25 years: See figure 3 below)   In total, 63% (n=40) patients developed a Ross-related failure around 12 years post-procedure. Of these, 31 patients had re-intervention on pulmonary conduit or pulmonary homograft at 11.9 years. At 1 and 25 years respectively, the freedom from a Ross related intervention (both surgical and percutaneous) was 96.7% and 26.3%. (see figure 4 below): Six percent (n=4) developed infective endocarditis de novo.

Exercise Capacity After Repair of Ebstein Anomaly in Adults. Morrical BD, Dearani JA, Bonnichsen CR, Taggart NW. Pediatr Cardiol. 2019 Apr;40(4):726-732. doi: 10.1007/s00246-019-02056-9. Epub 2019 Jan 30. PMID: 30701277 Similar articles  Take Home Points: Most patients reported symptomatic improvement after surgical repair of Ebstein anomaly – as assessed by NYHA class and self-reported symptoms. Formal exercise testing did not reveal objective evidence of functional improvement. Echo parameters showed improvement in terms of the degree of TR and RV size. Those on betablockers at ANY time had a reduced exercise capacity as measured by METs and VO2 Commentary by Dr. Blanche Cupido (Cape Town), section editor of ACHD Journal Watch:  The surgical repair techniques for Ebstein anomaly have evolved over the last few decades but timing of surgery remains variable. Though patients report symptomatic improvement, there are no objective functional capacity data for those patients post-repair in adulthood. This retrospective review, from the Mayo Clinic, aimed to describe the effect of repairing or replacing the tricuspid valve (TV) in Ebstein anomaly by comparing exercise test data in adults before and after surgery. They enrolled all patients with Ebstein anomaly who underwent tricuspid surgery at the Mayo Clinic between June 2007 and January 2015. All patients had both pre- and postoperative exercise test data and echocardiograms. Three hundred and twenty two patients had tricuspid surgery during the study period. Of these, 32 had pre-and post-exercise tests adequate for analysis. The mean age at time of surgery was 40 years old, 69% of the cohort was female. 19 patients had a ‘Cone’ repair 13 had a tricuspid valve replacement 26% were re-operations 75% were symptomatic prior to surgery   All patients had good surgical results with the tricuspid regurgitation being significantly reduced post-operatively (77% had severe TR pre-op; 91% had no/mild TR post-op) – p<0.001. Though the RV size did not normalize, it was significantly decreased. The NYHA class improved dramatically after surgery with 68% of patients improving to class I. There was no significant difference in the functional aerobic capacity, metabolic equivalents, exercise time or VO2max between the pre- and post-operative exercise tests.   Beta blockers had a significant effect on net exercise performance. Those patients who were never on a betablocker before, achieved higher METS and higher VO2max than those on betablockers. Functional aerobic capacity was not affected. The addition of betablockers did not alter pre-and post-exercise parameters. Furthermore, there was no association with pre-or post-operative arrhythmia and betablocker usage. There was no difference in exercise parameters between those who had a repair and those who had a tricuspid valve replacement. There was no difference in exercise capacity between those with a first repair vs a re-do repair.

Safety and effectiveness of home-based, self-selected exercise training in symptomatic adults with congenital heart disease: A prospective, randomised, controlled trial. van Dissel AC, Blok IM, Hooglugt JQ, de Haan FH, Jørstad HT, Mulder BJM, Bouma BJ, Winter MM. Int J Cardiol. 2019 Mar 1;278:59-64. doi: 10.1016/j.ijcard.2018.12.042. Epub 2018 Dec 17. PMID:  30594347 Similar articles   Take Home Points: Physical exercise is generally safe in symptomatic patients with congenital heart disease. Patients with complex congenital heart disease demonstrate more improvement than those with moderate congenital heart disease after undergoing exercise training. Commentary from Dr. M.C. Leong (Kuala Lumpur), section editor of ACHD Journal Watch:  Exercise training programmes have been shown to improve exercise capacity and the quality of life of patients with congenital heart disease (CHD). However, its effect on symptomatic patients with CHD is largely unknown. No study so far, has elucidated the beneficial or harmful effects of exercise training in this group of patients. This study aimed to evaluate the safety and efficacy of home based, unsupervised, self selected, execise training in symptomatic patients with CHD over a period of 6 months. This is a prospective, single centre, parallel group, randomised controlled trial which assigned 40 patients with NYHA II or III into two groups i.e the exercise group or the controlled group. Patients in the exercise groups were prescribed with exercise of a minimum of 3 sessions of 45 minutes. Patients in the controlled group were not prescribed with any exercise training. All patients were asked to continue habitual daily activities, even if these included regular physical exercise. During the study period, no patient experienced cardiac related events. There is a mariginal but statistically significant improvement in the peak VO2 in the exercise group by +1.6  ± 2.7ml/kg/min. The improvement is seen more in patients with severe CHD complexity compared to those with moderate CHD complexity (mean change : +3.0 ± 1.9 vs. −0.04 ± 2.5 ml/kg/min, p = 0.012). Meanwhile the control group showed no improvement in the peak VO2. The NTproBNP levels and the quality of life was measured subjectively via questionaires before and after study period – this remained unchanged in both groups. Although this study did not show a marked improvement in the exercise capacity in the exercise group, it has demonstrated that exercise in patients with congenital heart disease, even if they are in NYHA II or III, is safe. This will hopefully allay the concerns of the patients and the caregivers alike, on physical activities in this group of patients.

Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study. Maagaard M, Heiberg J, Redington AN, Hjortdal VE. Eur J Cardiothorac Surg. 2019 Oct 18. pii: ezz278. doi: 10.1093/ejcts/ezz278. [Epub ahead of print] PMID: 31625565 Similar articles Select item 31625562   Take Home Points: In young adults with small unrepaired ventricular septal defects (VSD), exercise capacity is diminished when compared with healthy controls, which can be explained by reduced biventricular contractility at rest and during exercise. Specifically, tissue Doppler parameters of left ventricle (LV) systolic function, including Isovolumetric acceleration (IVA), are diminished both at rest and during exercise in VSD patients when compared with healthy controls. Thus, LV contractile reserve is progressively decreased at higher workloads in VSD patient. Patients with small unrepaired VSD are at increased risk of long-term complications and should be followed in adult congenital heart centers. Commentary from Dr. Maan Jokhadar (Atlanta GA), section editor of ACHD Journal Watch:  Recent studies have demonstrated reduced exercise capacity in young patients with unrepaired small ventricular septal defects (shunt fraction < 1.5) and this is thought to be due to ventricular dysfunction from a small shunt over a prolonged period of time. Ventricular force – frequency relationships can be studied noninvasively using tissue Doppler techniques to reflect the dynamic myocardial response to exercise. This elegant study was conducted by Dr. Maagaard and colleagues from Aarhus, Denmark in collaboration with Dr. Redington in Cincinnati, OH, USA. They studied 34 unrepaired VSD patients and 28 healthy controls between the ages of 18 and 40. In the VSD group, 9 were muscular and 23 were perimembranous. All participants had normal resting ejection fraction, tricuspid regurgitation velocity less than 2.8 cm/sec, normal right atrial pressure, and no measurable aortic insufficiency. The average age was 27 years and baseline characteristics were comparable in the patient and control group, including height, weight, gender, body mass index, heart rate, blood pressure, as well as comparable daily exercise levels. All patients in the small VSD group had isolated VSD without prior surgical intervention and no associated congenital heart disease, arrhythmia, or syndrome. The median shunt fraction was 1.2. All participants had bicycle exercise echocardiogram with longitudinal incremental tissue Doppler imaging with workload increased until exhaustion. Tissue Doppler measurements were obtained in the apical 4 chamber from the basal septum and basal free walls of the LV and RV. At baseline, IVA was lower in VSD patients compared with controls in the septum, LV, and RV.  LV and RV peak S’ was also lower in VSD patients. However, septal S’, E’, and A’ were similar between VSD patients and controls. During supine bicycle ergometry, force-frequency relationship curves of IVA in VSD patients were lower than controls in the septum, RV, and LV.  This difference increased with intensifying workload. IVV and S’ of the RV, LV, and septum were also lower in VSD patients during exercise. Smaller shunts had higher LV IVA but this inverse relationship was not true for the septum or RV. Higher RV S’ correlated with better exercise capacity in VSD patients but not in controls. These findings may be explained by the increased left ventricle volume loading that occurs, even with small shunts over a long period of time. Clearly, even small shunts may be hemodynamically significant in the long run because of the increased LV volume load, left atrial dilation, and amplification of diastolic dysfunction with age. Though a lower threshold for VSD closure could potentially mitigate or avoid the adverse changes associated with small shunts, additional studies are needed before such a conclusion can be reached. However, this study does bolster the argument that unrepaired VSD patients should be followed by a specialized center for adult congenital patients. This important study adds to the growing body of literature regarding the long-term hemodynamic consequences of unrepaired VSD and increases our understanding in this area. Tissue Doppler Parameters during systole and diastole AT: Acceleration time (sec) IVV: Isovolumetric velocity (cm/sec) IVA: Isovolumetric acceleration (cm/sec2) IVA = IVV/AT (cm/sec2) Peak S’ velocity (cm/sec) IVCT: Isovolumetric contraction IVRT: Isovolumetric relaxation E’: Early relaxation A’: Associated with atrial contraction ET: ejection time  

All-cause mortality and survival in adults with 22q11.2 deletion syndrome. Van L, Heung T, Graffi J, Ng E, Malecki S, Van Mil S, Boot E, Corral M, Chow EWC, Hodgkinson KA, Silversides C, Bassett AS. Genet Med. 2019 Oct;21(10):2328-2335. doi: 10.1038/s41436-019-0509-y. Epub 2019 Apr 5. PMID: 30948858 Free PMC Article Similar articles Select item 31315938 Take Home Points: 2 deletion is the most common microdeletion syndrome and frequently encountered in patients with congenital heart disease – particularly conotruncal anomalies. Little is known about the longer-term survival of adult patients with 22q11.2 deletion syndrome. This was a retrospective review of 309 adults with 22q11.2 deletion syndrome and their 1014 unaffected parents/siblings. 2 deletion syndrome is associated with almost 9x independent risk of mortality compared to siblings without 22q11.2. (HR 8.86, 95% CI 2.87-27.37). Of the patients with 22q11.2 deletion there were 31 deaths at a median age of 46 years (range 18 -69 years). As one would expect, patients with ‘major ‘congenital heart disease had shorter survival than patients with non-major congenital heart disease. Probability of survival of patients with 22q11.2 and major congenital heart disease to live to age 40 and 50 years was approximately 82% and 63% vs 98% and 85% in patients without major congenital heart disease. Commentary from Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch:   22q11.2 deletion syndrome is thought to be inherited in 1 in 3000-4000 live births. Penetrance is very high but with wide phenotypic variability. There has been little investigation of the importance of 22q11.2 deletion in adults and this retrospective analysis sought to address what implications 22q11.2 has on survival in affected subjects compared to their siblings/parents.  Patient demographics and outcomes Patients were identified from a specialty clinic for adults with 22q11.2, via referrals or screening of patients with congenital heart disease (CHD). Over four fifths of patients were Caucasian (n=260) and 52% (n=161) were women. 469 siblings and 545 parents without 22q11.2 were enrolled as comparators. ‘Major’ congenital heart disease (n=112) was defined as persons with at least moderate complexity CHD, most of whom had tetralogy of Fallot (n=80). 309 subjects >17 years old with 22q11.2 deletion agreed to participate – of these, just over a third (n=112) had ‘major’ CHD. The primary outcome measure was all cause mortality. Medical records and postmortem studies were reviewed to establish cause of death. Follow up was for a relatively modest median period of 5.3 years (range 0.1-21.5 years). During follow up, 31 subjects with 22q11.2 deletion died at a median age of 46 years old (range 18-69 years) - mostly resulting from cardiac causes (n=22) (Table 1). In comparison, 6 subjects without 22q11.2 deletion died at a median age of 58 years old (range 24-83 years old). Controlling for other significant co-variables (such as the presence of major CHD), there was an independent relationship between survival and presence of a 22q11.2 microdeletion (Table 2).  Subjects with 22q11.2 deletion had worse survival if they had ‘major’ CHD versus ‘non-major’ CHD (Figure 1). Table 1 Cause of death in 31 adults with 22q11.2 deletion syndrome and relationship to CHD complexity  Table 2 Cox regression models for mortality risk in 309 adults with 22q11.2 deletion syndrome  

Pathophysiologic and Prognostic Implications of Right Atrial Hypertension in Adults With Tetralogy of Fallot. Egbe AC, Bonnichsen C, Reddy YNV, Anderson JH, Borlaug BA. J Am Heart Assoc. 2019 Nov 19;8(22):e014148. doi: 10.1161/JAHA.119.014148. Epub 2019 Nov 8. PMID: 31701796 Free Article Similar articles Select item 31742886   Take Home Points: Increasing RAP in symptomatic patient with TOF —an integrated measure of right heart compliance—was associated with worsening exercise capacity, disease severity and cardiovascular adverse events. RAP can be used for risk stratification in symptomatic TOF patients and can have potential clinical implications regarding type and timing of intervention. Furthermore, assessment of IVC size and collapsibility can be used for noninvasive estimation of RAP and correlated with event-free survival. Commentary by Dr. Soha Romeih (Aswan), section editor of ACHD Journal Watch:  Right ventricular (RV) systolic dysfunction frequently develops in adults with repaired TOF and is one of the criteria used to guide the decision for PVR. RV diastolic dysfunction typically precedes systolic dysfunction, suggesting that this might be an earlier indicator for ventricular dysfunction, but the assessment of RV diastolic function is challenging, and there are no validated noninvasive indices of RV diastolic function in the TOF population. Increased RAP is a predictor of mortality in patients with heart failure due to acquired heart disease. It seems likely that TOF patients might have abnormal RA and RV mechanics caused by myocardial injury and remodeling because of prior surgical and ongoing hemodynamic insult, thus causing abnormal RAP. Egbe et al, in the current study hypothesized that RAP, as assessed by the gold standard of invasive hemodynamic assessment, would be associated with disease severity and cardiovascular adverse events in adults with TOF. Methods This is a retrospective cohort study, and the target population is symptomatic patients with repaired TOF who underwent right heart catheterization at the Mayo Clinic Rochester (Minnesota) from 1990 till 2017. Patients with tricuspid valve prostheses were excluded. The primary study objective was to determine the association between RAP and disease severity indices, assessed across 3 clinical domains: (1) Aerobic capacity (percentage of predicted peak oxygen consumption [VO2]) (2) Arrhythmias, Atrial/ventricular arrhythmia - defined as documented atrial fibrillation, atrial flutter/tachycardia, or non-sustained ventricular tachycardia (3) Heart failure hospitalization - defined as an admission for volume overload (pulmonary congestion and/or peripheral edema) requiring intravenous diuretics. The secondary study objective was to determine the association between RAP and a. cardiovascular adverse events - defined as sustained ventricular tachycardia, resuscitated or aborted sudden cardiac death, heart transplantation, or b. all-cause mortality. Exploratory analysis was performed to determine the correlation between RAP and echocardiographic indexes of RV diastolic function Tricuspid inflow early diastolic velocity/tricuspid inflow late diastolic velocity (E/A) Tricuspid inflow early diastolic velocity/tricuspid annular tissue Doppler early systolic velocity (E/e’), Tricuspid inflow deceleration time (DT) Inferior vena cava (IVC) size. IVC was defined as IVC >21 mm, and reduced collapsibility during inspiration was defined as <50% decrease in IVC diameter during inspiration.   Cardiac Cath Total pulmonary resistance = mean PAP/pulmonary blood flow index PA compliance index = the ratio of RV stroke volume index/PA pulse pressure Pulmonary elastance = the ratio of PA systolic pressure/stroke volume index. LV transmural pressure, which reflects the net distending pressure that favors LV filling, = PA wedge press minus RAP.   Echocardiography Only echocardiograms performed within 7 days from the time of cardiac catheterization were analyzed for this study. Outcomes Assessment All exercise tests were required to be performed within 6 months from the time of cardiac catheterization. Percentage of predicted peak VO2 was assessed using upright treadmill cardiopulmonary exercise testing, with maximum effort defined as respiratory quotient >1.1. Atrial/ventricular arrhythmia and heart failure hospitalization status were ascertained in 100% of patients as of December 31, 2017, using the date of the last clinic visit. All-cause mortality was ascertained using the Mayo Clinic registration database and Accurint, an institutionally approved location service, in 100% of patients as of December 31, 2017.   Results Clinical and Hemodynamic Data A total of 231 ambulatory patients with TOF underwent right heart catheterization within the study period. 6 were excluded because they had tricuspid valve prostheses. RPA and hemodynamic cath: Mean RAP was 10.7±5.2 mm Hg, and median RAP was 10 mm Hg. There was good correlation between RAP and RV afterload, as measured by PA compliance, PA elastance, and total pulmonary resistance (Figure 1), but no correlation between RAP and RV outflow tract (RVOT) obstruction, suggesting that the association between RAP and RV afterload is more likely due to pulmonary vascular dysfunction (both PA and capillaries) and left atrial hypertension. Similarly, RAP correlated with LV transmural pressure and cardiac output (Figure 1). RAP and Disease Severity Indexes Of 225 patients, 95 (42%) experienced atrial/ventricular arrhythmias (63 with atrial fibrillation, 56 with atrial flutter/ tachycardia, and 50 with non-sustained ventricular tachycardia) during the follow-up period. RAP was associated with atrial/ventricular arrhythmia occurrence. An exploratory analysis was performed to assess the correlation between RAP and ventricular arrhythmias. An association between RAP and ventricular arrhythmia occurrence were noted. There were 26 patients (12%) with heart failure hospitalizations, and RAP was associated with heart failure hospitalization). Of the 128 patients (57%) with exercise test data, the mean peak VO2 and percentage of predicted peak VO2 were 21±6 mL/kg per minute and 62±15%, respectively. There was an inverse correlation between RAP and percentage of predicted peak VO2 (Figure 2). RAP and Cardiovascular Adverse Events Mean follow-up from the time of cardiac catheterization was 7.3±5.8 years, yielding total follow-up of 1642 patient-years. In total, 97 patients (43%) underwent PVR during follow-up. During this period, there were 28 cases of sustained ventricular tachycardia, 4 cases of aborted sudden cardiac death, 4 patients who underwent heart transplant, and 35 patients who died. The cause of death was end-stage heart failure (n=20), arrhythmic death (n=6), postoperative death after cardiac surgery (n=3), bleeding- or stroke-related death (n=1), malignancy (n=1), sepsis (n=1), and unknown (n=3). A cardiovascular adverse event end point occurred in 55 patients (24%), yielding an event rate of 3.2 per 100 patient-years. The 10-year rate of freedom from cardiovascular adverse events was 74% for the entire cohort. RAP >10 mm Hg provided the best prediction of cardiovascular adverse events. Patients with RAP >10 mm Hg had lower event-free survival compared with those with RAP ≤10 mm Hg (Figure 3). RAP was a statistically significant predictor of cardiovascular adverse events Echocardiographic Predictors of RAP Of all diastolic function indexes assessed, IVC size and collapsibility provided the best detection of elevated RAP (RAP >10 mm Hg).  Dilated IVC had the best sensitivity to detect elevated, whereas dilated IVC with reduced inspiratory collapse had the best specificity to detect elevated RAP Discussion The current study showed significantly worse outcomes in patients with high RAP (RV diastolic dysfunction and/or RA dysfunction) despite having similar severity of RVOT lesion (pulmonary regurgitation and stenosis). These data suggest that RAP might be considered when deciding on timing of RVOT intervention in patients with borderline indications for intervention, especially when symptoms (exercise intolerance, arrhythmia, and heart failure) seem disproportionate to the severity of RVOT lesion. Furthermore, RAP may also be considered during sudden death risk stratification because of its correlation with occurrence of ventricular arrhythmia occurrence.   Limitations The current study was based on a selected cohort of patients who underwent cardiac catheterization, and this approach may limit the generalizability of the results. Although this study will not be appropriate for describing the prevalence of diastolic dysfunction, the clinical implications of RV diastolic dysfunction reported in this study are still pertinent when dealing with symptomatic patients.  

Elevated ventricular filling pressures and long-term survival in adults post-Fontan. Miranda WR, Hagler DJ, Taggart NW, Borlaug BA, Connolly HM, Egbe AC. Catheter Cardiovasc Interv. 2019 May 30. doi: 10.1002/ccd.28340. [Epub ahead of print] PMID:  31145542 Similar articles Take Home Point: Though elevated VEDP portends a poor long-term prognosis, PAWP was better in predicting mortality amongst the many other factors we assess in Fontan patients.  However, if it is normal, we cannot necessarily be reassured. Commentary by Dr. Helen Parry (Leeds, United Kingdom), section editor of ACHD Journal Watch:  Diastolic dysfunction is part of the natural history of patients with Fontan palliations – ventricular end diastolic pressures (VEDP) and pulmonary capillary wedge pressure (PCW) serve as surrogates for left atrial pressures (LAP). Data pertaining to the haemodynamic predictors of survival in this cohort are limited. This study from the Mayo clinic, enrolled 148 adult patients with Fontan circulation who underwent cardiac catheterisation within an 18-year period (December 1999 to November 2017). Patients with atrioventricular prostheses were excluded. Findings with respect to ventricular end diastolic pressure and pulmonary artery wedge pressure were correlated with mortality. Mean age at the time of Fontan was 10.1±8.1 years. The mean ventricular ejection fraction was 51.1% and the atrioventricular regurgitation was more than moderate in 24 patients (16.2%). Mean VEDP was 11.5 ±4.7mmHg and PAWP 10.6 ± 4.5 mmHg. PAWP correlated better with Fontan pressures compared to VEDP (correlation coefficient 0.82 vs 0.63, p<0.0001). Patients were followed up for a mean of 6.0±4.8 years. A total of 45 deaths occurred during this period (30.4%). Survival was greater in those with a VEDP <12 compared to a VEDP >12 mmHg (p=0.02). Similarly this held true for patients with a PCWP using a cut-off of 12mmHg. There was no survival difference in those patients with a VEDP > 12 mmHg vs VEDP <12mmHg if the PCWP was <12mmHg. Pulmonary artery wedge pressure was a better predictor of mortality than ventricular end diastolic pressure. Positive aspects of the study: Large sample size for a Fontan study Reproducible methodology Offers a tool for helping to predict outcome in Fontan patients Negative aspects of the study: The team point out that many patients who died after the catheter study did not have raised PAWP.  This was far in excess of what would be expected for background, non-Fontan related deaths. No potential measures are suggested to prevent deterioration.