Adult Congenital Heart Disease

Role of Inferior Vena Cava Dynamics for Estimating Right Atrial Pressure in Congenital Heart Disease. Egbe AC, Connolly HM, Pellikka PA, Anderson JH, Miranda WR. Circ Cardiovasc Imaging. 2022 Sep;15(9):e014308. doi: 10.1161/CIRCIMAGING.122.014308. Epub 2022 Sep 20.PMID: 36126125 Take Home Points: In this retrospective, single center study, the authors aimed to correlate between invasively measured right atrial pressures (RAP) and non-invasively assessed RAP using echocardiographic measurement of the inferior vena cava (IVC) diameters and inspiratory collapsibility.  Echocardiographic images from 918 ACHD patients aged>18 years who had a right heart catheterization within 7 days of the echo study were included, and patients with a Fontan circulation were excluded. The study cohort was divided into derivation and validation cohorts, each consisting of 459 patients. The definition for elevated RAP was >10 mm Hg. The prognostic implications of elevated RAP were also compared between the invasive and non-invasive measurement methods. For this purpose, a composite end point consisting of heart failure hospitalization, heart transplant, or cardiovascular death occurring from the time of cardiac catheterization to the end of the study period was used. The most common congenital heart lesions were tetralogy of Fallot (n=264, 29%), coarctation of aorta (n=120, 13%), and Ebstein anomaly (n=71, 8%). Tetralogy of Fallot was more common in the derivation cohort but the other diagnoses were equally distributed between the 2 groups. Table 1 shows the hemodynamic measurements of the cohort, divided into the derivation and validation groups. Commentary from Dr. Yonatan Buber (Seattle, USA), section editor of ACHD Journal Watch Table: invasive and noninvasive hemodynamic indices of the study patients. As shown in Table 2, the correlation between the maximal diameter of the IVC (IVC max), the minimal diameter of the IVC (IVC min) and the collapsibility index of the IVC (IVCCI) and the invasively measured RAP were excellent. Similar strong correlations were present when the IVC diameters were indexed to the body surface area. Reproducibility of the reads was excellent with minimal inter-observer variability. Table 2. Correlation Between IVC Dynamics and Invasively Measured RAP in the Derivation Cohort Using logistic regression and receiver operating characteristic curve, IVC max of 1.8 cm, IVC min of 1.2 cm and IVCCI of 60% were found to be the best discriminatory points for invasively measured elevated RAP of >10 mm Hg. However, IVCCI<60% had the best discriminatory power to identify patients with increased RAP (AUC 0.84 [95% CI, 0.80–0.88]; P<0.001), with IVCCI <60% providing the optimal cutoff point to detect increased RAP with a sensitivity of 93% and specificity of 89%. RAP was estimated from IVC dynamics using the formula: (RAP=16.89–0.12 [IVCCI]) Similarly, in the validation cohort,  IVCCI <60% had a more robust diagnostic performance as compared with IVC max >1.8 cm and IVC min >1.2 cm. Furthermore, IVCCI <60% had superior diagnostic performance as compared to the American Society of Echocardiography (ASE) criteria for the diagnosis of elevated RAP (IVC max >2.1 cm and IVCCI of<50%) Several sub-group analyses were performed, and showed that among patients with right heart disease, IVCCI <60% performed better the ASE recommended criteria for the diagnosis of elevated RAP. In patients without right heart disease and in patients with>moderate degree of tricuspid valve regurgitation this effect was much less robust. There was no difference between men and women and between patients who did or did not undergo prior sternotomies or thoracotomies. During a median follow up of 6.9 years, 25% of the study patients experienced an outcome event. As shown in Table 6 of the manuscript, invasively measured RAP and estimated RAP based on IVCCI had a comparable prognostic power, while estimated RAP based on ASE criteria had a less robust prognostic power. Table 6. Multivariable Cox Models Showing Risk Factors Associated with Cardiovascular Events Right atrial pressure is a good metric surrogate of right heart function and reflects right ventricular diastolic function, right atrial compliance and general function, and overall volume status. Due to various reasons that include the native anatomical lesion, prior surgeries, lung disease and others, these factors are often different and abnormal in ACHD patients, particularly those with lesions involving the right heart. The finding by Egbe et al. that the cutoff values for the diagnosis of elevated RAP in a large group of ACHD patients were different from those used for the general population should therefore come as no surprise. This is a meticulously performed study that identifies a new cutoff value in the form of IVCCI <60% as the best method to diagnose elevated RAP in ACHD patients, especially those with right heart disease. The authors also provide a useful formula (RAP=16.89–0.12 [IVCCI]) which can be used to divide the patients into 3 categories based on estimated RAP (0–5, 6–10, and >10 mm Hg). The lower cutoff values of IVC max (1.8 cm in this study vs 2.1 cm in the general population) to diagnose elevated RAP likely reflect high incidence of low-compliant right atria and right ventricles in the population, which is more prominent in patients with right heart disease. The reason why an IVCCI<60% (a value that is higher than traditional 50% used by the ASE in the general population) was found to have the strongest correlation with elevated RAP in not entirely clear. A possible explanation offered by the authors is that ACHD patients are younger and are potentially able to generate more negative intrathoracic pressure, and hence a lower IVC collapsibility will correlate with higher RAP as compared to the older patients with acquired heart disease. While this is a possibility, it is also well accepted that accurate measurement of IVC collapsibility is notoriously difficult and is associated with high rates of inter-observer variability (although apparently not in this study).  Outside validation of this study’s results will be needed to confirm this finding and to make it generalizable to other medical centers around the world.

Chronic kidney disease in patients with congenital heart disease: a nationwide, register-based cohort study. Gillesén M, Fedchenko M, Giang KW, Dimopoulos K, Eriksson P, Dellborg M, Mandalenakis Z. Eur Heart J Open. 2022 Sep 2;2(5):oeac055. doi: 10.1093/ehjopen/oeac055. eCollection 2022 Sep.PMID: 36213331 Free PMC article. Commentary by Dr. Helen Parry (Leeds, UK), section editor of ACHD Journal Watch: Introduction: Whilst acute kidney injury is a common complication following cardiac surgery for congenital heart disease, it is unclear whether these patients go on to develop chronic kidney disease (CKD).  Studies show there are relatively high rates of CKD in patients with congenital heart disease. Methods: Data were taken from the Swedish National Patient Register and the cause of death register, patients with congenital heart disease born between 1970 and 2017 were identified.  Each case was matched to 10 controls for age and sex taken from the Swedish population register. Chronic kidney disease, acute kidney injury and hypertension were defined by presence of the relevant ICD codes on the register. Patients with congenital heart disease were analyzed as a group and categorized into 6 groups: Cono-truncal defects including common arterial trunk, aortopulmonary septum defect and transposition of the great arteries. Severe, non-cono-truncal defects including endocardial cushion defect, common ventricle and hypoplastic left heart syndrome. Coarctation of the aorta Ventricular septal defects Atrial septal defects All other heart and  circulatory anomalies In the presence of multiple diagnoses, the classification was based on the most severe pathology. Analysis was performed using the Chi squared test for categorical variables and the Student’s t test for nominal variables. Increased rate of CKD was reported per 100000 person years. Death from all causes was accounted for as a competing risk.  Cox regression models were used to generate hazard ratios with confidence intervals accounting for acute kidney injury, hypertension, and diabetes.  Patients were divided into age categories for regression modelling: 0-17 years, 18-39 years and >40 years. Results A total of 71 936 patients with congenital heart disease were identified: 50.2% were male Mean birth year 1999 Most common lesions VSD (31.9%) and all other heart and circulatory abnormalities (30.2%) During a median follow up of 13.5 years for patients and 15.5 years for controls, almost 0.5% of patients with congenital heart disease developed CKD compared to 0.1% controls.  Hazard ratios for CKD in patients with congenital heart disease are provided below in the table adapted from the text: Lesion GroupNumber (%) patients with congenital heart disease and CKDHazard ratio for CKD (95% CI)Adjusted hazard ratio for CKD accounting for hypertension, AKI and diabetes mellitus (95% CI)All Congenital heart disease379 (0.5)6.41 (5.65-7.27)4.37 (3.83-5.00)Conotruncal defects39 (0.7)7.62 (5.17-11.24)6.62 (4.43-9.89)Severe non-conotruncal defects34 (0.8)11.31 (7.37-17.36)6.79 (4.24-10.82)Coarctation25 (0.7)9.66 (5.68-16.42)6.74 (3.62-12.55)VSDs81 (0.4)5.39 (4.13-7.05)4.31 (3.25-5.72)ASDs64 (0.4)7.40 (5.36-10.21)6.57 (4.67-9.26)Other heart and circulatory abnormalities136 (0.6)5.58 (4.55-6.86)3.59 (2.88-4.49) The most prevalent risk factor before a CKD diagnosis was hypertension (21.1%, n=80), followed by previous acute kidney injury (15.0%, n=57) then diabetes mellitus (4.2%, n=16). Discussion and clinical implications: The take home message was that patients with congenital heart disease have a 6-fold increase in risk of developing CKD.  However, the incidence of CKD in congenital heart disease appears to be lower than in previous cohort studies.  The patients with the greatest likelihood of developing CKD were those with conotruncal abnormalities or severe defects that were not conotruncal abnormalities.  This is thought to relate to chronic hypoperfusion, maladaptive repair and fibrogenesis. The risk of chronic kidney disease was higher in patients born 1997-2017 compared to 1970-1996.  It was though this could be partly explained by survival bias.  The authors point out some of the limitations of their study including the uncertainty relating to ICD codes. They suggest the clinical impact of the study will be to prompt further work looking at potential interventions to prevent development on CKD in this group. Positive points: Relatively large sample size for a study in congenital heart disease Acknowledgment of the multiple other factors influencing development of chronic kidney including hypertension and diabetes Showed awareness of limitations Limitations/ negative aspects: Retrospective cohort study, inherently limited The coding of the types of congenital heart disease could be criticized: the category “all other heart and circulatory abnormalities” is too broad, there is also a huge spectrum of severity within the other categories. No information on the severity of CKD, how much impact does this diagnosis actually have? What percentage of congenital heart disease patients are on long term renal replacement therapy? Nephrotoxic drugs are not accounted for.

26. PMID: 34118376   Long-term Outcomes of Adults With Single Ventricle Physiology Not Undergoing Fontan Repair: A Multicentre Experience.   Buendía-Fuentes F, Gordon-Ramírez B, Dos Subirà L, Merás P, Gallego P, González A, Prieto-Arévalo R, Segura T, Rodríguez-Puras MJ, Montserrat S, Sarnago-Cebada F, Alonso-García A, Oliver JM, Rueda-Soriano J.Can J Cardiol. 2022 Jul;38(7):1111-1120. doi: 10.1016/j.cjca.2021.06.001. Epub 2021 Jun 9.PMID: 34118376   Take Home Points   Univentricular heart patients, not having undergone a Fontan palliation were classified into 3 types in this large 7 centre study from Spain; Eisenmenger physiology, those with surgical aortopulmonary shunts, and those with restricted pulmonary blood flow. Mortality occurred in 22.6% (n=33) over 7.3+/- 4.1 years of follow-up with sudden death being most common (36.4%) versus heart failure related (27.%). Five and 10 year survival was 86% and 74% respectively overall, patients with restrictive pulmonary blood flow doing better. Four baseline risk factors, after adjustment for age, ventricular morphology, group and NYHA class, predicted increased mortality: Moderate or more atrioventricular regurgitation Thrombocytopaenia (<150x103/mm3) Bundle branch block (QRS>120ms) Renal dysfunction (<60mls/min/1.73m2) Patients with restricted pulmonary blood flow had lower mortality (p=0.019), heart failure admissions (p=0.017) and fewer arrhythmias (p=0.028).   Commentary by Dr Simon MacDonald (London, UK), section editor of ACHD Journal Watch:   Long-term survival and cardiovascular outcomes in adult patients with a single ventricle, who have not undergone a Fontan palliation, have been unclear and understudied. Single ventricle patients include those who are not suitable for biventricular correction with the ventricular mass then supporting both systemic and pulmonary circulations. Most now undergo a Fontan palliation but some are not suitable and some present late. In perhaps the largest study of these patients, Francisco Buendía-Fuentes and team performed a retrospective review of data from 7 centres in Spain of 146 patients over a 21 year period. They subdivided the cohort into the groups of Eisenmenger (26 or 17.8%), those with restricted pulmonary flow (86 or 58.9%) and those with aortopulmonary shunts (34 or 23.3%) with death as the main endpoint and secondary endpoints of transplantation, heart failure admissions and transplantation, endocarditis, atrial arrhythmias, stroke, and brain abscesses.   Data was obtained from centre databases, kept prospectively, with charts reviewed from May 1999 to March 2020. The 146 patients studied had a mean age at presentation 32.5±11.1 years. Double-inlet left ventricle was the most common anatomy (48.6%), followed by tricuspid atresia (19.2%), with left ventricular morphology being most common (74%).   They had a mean follow-up of 7.3±4.1 years with 33 deaths (22.6%). Five and 10 year survival was 86% and 74% respectively in the whole cohort. Survival was different between the three groups (p=0.019) as below:   Patients with restricted pulmonary flow had the best survival with rate 93% and 81% at 5 and 10 years.   Univariate analysis suggested lower saturations, NHYA class and ventricular function were important, but not in the multivariate analysis which suggested moderate atrioventricular valve regurgitation, platelet count <150x103/mm3, GFR <60mls/min/1.73m2 and QRS>120ms predicted increased mortality. Interestingly ventricular morphology was not predictive of death.   Over a third (34.2%) were admitted with heart failure symptoms, 11 (7.5%) received heart transplant (10 heart, 1 heart/lung), with mean 5 year survival post-transplant 78%.  Atrial flutter/ fibrillation was seen in 28 (19.2%) patients with 15 having electrophysiology study. Of the 28, 8 of these patients had a stroke, two underwent transplantation and 9 died. Those with a restricted pulmonary flow had less atrial arrhythmias than the other groups (p=0.028).   These patients all have long-term sequalae of cyanotic congenital heart disease, developing a multisystem disorder. The population studied was large but there were non-standardised protocols between the centres and many patients seemed lost to follow-up initially (48%) with 32% followed-up by non ACHD cardiologists. Mortality and event rates of patients before entry to the study are not known, with survivorship bias present. Also survival outcomes of patients not followed in ACHD centres was unclear. The effect of developing new risk factors over time and the impact of particular treatments (like heart failure medications, valve replacement) was not studied and would need a larger still study group. The extent of advance care planning was also unclear. This multicentre study was however successful in reporting outcomes in this small and unique patient group and potential factors that influence death and cardiac outcomes, with the accompanying editorial emphasising the need for these patients to be cared for in specialist ACHD centres.

25. PMID: 34706905   Outcomes among adult survivors of total cavopulmonary Fontan palliation for single ventricle.   Anigwe C, Yogeswaran V, Moon-Grady A, McAllister S, Aggarwal A, Blissett S, Harris IS, Kouretas PC, Mahadevan VS, Sabanayagam A, Agarwal A.Heart. 2022 Jul 13;108(15):1209-1215. doi: 10.1136/heartjnl-2021-319760.PMID: 34706905   Take Home points: Adverse outcomes seen in 54.4% of TCPC patients with up to 34 year follow-up post palliation The most frequent adverse events were arrhythmias, pacemaker/ICD implantation, and thromboembolic events Higher METS and peak heart rate at exercise was associated with fewer adverse events. Adverse outcome-free survival rates were 89% at 1o year, 60% at 20 years and 24% at 25 years post-Fontan palliation. ECC Fontan was an independent predictor of adverse events after adjusting for other risk factors.   Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch:   Total cavopulmonary circulation (TCPC) has become the preferred surgery for single ventricle palliation. Robust data on the prevalence and predictors of long terms outcomes is lacking. The existing data is limited by predominantly looking at the paediatric population, focusing on peri-operative and short term outcomes, with little info in the adult population. Furthermore, most studies are heterogenous, in that the TCPC population is not studied in isolation, not is morbidity assessed well (older studies focused predominantly on mortality outcomes).   This single center retrospective study aimed to assess the prevalence and factors associated with long term outcomes in adults who had undergone the TCPC procedure between 1 January 2000 and 1 July 2019. Adverse outcomes assessed included: arrhythmia, pacemaker or ICD placement, liver cirrhosis, protein losing enteropathy (PLE), heart failure hospitalization or thromboembolic complications or death.   The analysis included 160 patients, of which 73.1% had an extra-cardiac conduit (ECC). The underlying pathologies included: tricuspid atresia (27.5%), hypoplastic left heart syndrome (25%), double-inlet LV (19.4%), double-outlet RV (10%), PA-IVS (5.62%), Ebstein’s anomaly (3.12%), hypoplastic right heart syndrome (1.88%), TGA (1.25%), pulmonary atresia (0.62%), heterotaxy (5.62%).   The TCPC’s were done between July 1985 and December 2011. Median age at TCPC was 4.7 years and the median duration to last follow-up was 17.5 years. Apart from  lower METs and peak heart rate, there were no significant differences in the cardiac diagnostic data between the group that experienced adverse events and those who did not.   Adverse outcomes were observed in 87 patients. Patients with adverse events were older, had a longer time since the TCPC operation and had a fenestration (Table 1).     The most frequently observed complications were arrhythmias (37.5%), pacemaker/ICD implantation (21.3%), and thrombo-embolic events (14.4%) (Figure 2)     The median adverse outcome-free survival was 22.9 years after TCPC procedure.   Adverse outcome-free survival was 89% at 10 years, 60% at 20 years and 24% at 25 years post TCPC palliation surgery. Unadjusted analysis showed non-white race and extra-cardiac conduit (ECC) to have worse outcome-free survival. Type of ventricle or presence of a fenestration was not a predictor of poor outcome. (Figure 3)     When adjusted for age, race, type of Fontan, systemic ventricle type and fenestration, ECC Fontan was independently associated with a greater risk for adverse outcome. This held true for the composite of all adverse outcomes, arrhythmias, cirrhosis, pacemaker/ICD implantation, and other. (Figure 4)      

11. PMID: 35879153   Prevalence of Metabolic Syndrome in Young Adults With Congenital Heart Disease. Umapathi KK, Thavamani A, Bosco G, Dhanpalreddy H, Nguyen HH.Am J Cardiol. 2022 Sep 15;179:90-95. doi: 10.1016/j.amjcard.2022.05.031. Epub 2022 Jul 22.PMID: 35879153   Take Home Points: Adults with congenital heart disease has an increased risk of developing metabolic syndrome The young adults have a higher risk of metabolic syndrome and its risk factors compared to the general population. When compared to normal controls, the risk of metabolic syndrome in descending order: Severe ACHD > Moderate ACHD > control.   Commentary from Dr. MC Leong (Kuala Lumpur), section editor of ACHD Journal Watch:   Adults with congenital heart disease (ACHD) have been shown in cohort studies to be at increased risk of developing metabolic syndrome (MetS), a cluster of metabolic abnormalities that increase the risk of cardiovascular disease and type 2 diabetes mellitus (1-3). Several factors have been implicated in the increased risk of MetS in ACHD, including activity restrictions, sedentary lifestyle, obesity and Fontan circulation (3,5).   This study aimed to study the prevalence of MetS in young adults aged 20-39 years in the United State using a large real-world population database. Patients were categorized into moderate and severe forms of ACHD based on ACHD anatomic and physiologic classification. As there were concerns of inaccuracies in the diagnosis of the mild form of ACHD, only moderate and severe forms of ACHD were analyzed. Diagnosis of MetS was made using a modified version of the International Diabetes Federation’s criteria.   In the study, the ACHD group was generally found to have a significantly higher risk of MetS (Table 3). Interestingly, the odds were higher in men and the 20-24 age group (Table 1). Tetralogy of Fallot and aortic arch anomalies were the most common CHD diagnoses in the ACHD group (Table 2). The severe ACHD group had a higher risk of MetS than the moderate ACHD group (Table 4, Figure 2). The ACHD group had higher odds of individual components of MetS, such as type 2 diabetes, family history of coronary artery disease, atrial fibrillation, obstructive sleep apnea, and pulmonary hypertension (Table 3). However, they had lower odds of risk factors for atherosclerotic cardiovascular disease, such as male sex, smoking, obesity, and chronic kidney disease. There was no significant difference in the prevalence of coronary artery disease between the ACHD and control groups.           Overall, the study highlights the importance of screening MetS in individuals with ACHD, particularly those with severe CHD and targeting risk factors for MetS in this population. Similar findings were found in a study with a similar study design, but with a smaller sample size (3). However, being a populational study, the study has its own flaws, for example, in the definitions of some of the variables, e.g. a high BMI does not equate to obesity. Also, the study provides data but is unable to explain some of the findings. For example, there was an unusually higher prevalence of MetS in the younger patients (age 20-24 years) in the cohort; and the finding of a higher prevalence of fasting hyperglycemia and a lower Type 2 diabetes in the ACHD group compared to control, all of which was not explainable in this study.   References: 1. Fyfe A, Perloff JK, Niwa K, Child JS, Miner PD. Cyanotic congenital heart disease and coronary artery atherogenesis. Am J Cardiol 2005;96:283–290. 2. Shin D, Kongpakpaisarn K, Bohra C. Trends in the prevalence of metabolic syndrome and its components in the United States 2007−2014. 3. Deen JF, Krieger EV, Slee AE, Arslan A, Arterburn D, Stout KK, Portman MA. Metabolic Syndrome in Adults With Congenital Heart Disease. J Am Heart Assoc. 2016 Feb 12;5(2):e001132. 4. Niwa K. Metabolic syndrome in adult congenital heart disease. Korean Circ J 2019;49:691–708. 5. Chung ST, Hong B, Patterson L, Petit CJ, Ham JN. High Overweight and Obesity in Fontan Patients: A 20-Year History. Pediatr Cardiol. 2016 Jan;37(1):192-200.  

Peak Oxygen Uptake on Cardiopulmonary Exercise Test Is a Predictor for Severe Arrhythmic Events during Three-Year Follow-Up in Patients with Complex Congenital Heart Disease. Von Sanden F, Ptushkina S, Hock J, Fritz C, Hörer J, Hessling G, Ewert P, Hager A, Wolf CM.J Cardiovasc Dev Dis. 2022 Jul 4;9(7):215. doi: 10.3390/jcdd9070215.PMID: 35877577    Take Home Points: Risk stratification for sudden cardiac death (SCD) and primary prevention ICD therapy in patients with complex congenital heart disease is challenging. This single-centre retrospective study of 1194 patients with complex CHD evaluated the ability of a range of measurements collected during routine cardiopulmonary exercise testing (CPET) to aid in the risk assessment of SCD over a three-year follow up period. Severe arrhythmia was documented in 97 patients (8.1 %/3 years), with independent risk factors being older age and low peak oxygen uptake (VO2peak) on multivariate analysis. The authors thus suggest considering age and VO2peak in the risk stratification of SCD and the individualized decision for primary prevention ICD implantation in patients with complex CHD. The data from this study has a number of limitations and will not result in a significant change in clinical practice, however it does endorse the large body of literature supporting the use of CPET in the overall risk stratification of patients with CHD.   Commentary by Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:  Patients with complex CHD carry a life-time elevated risk for severe arrhythmia and sudden cardiac death (SCD), with up to 26 % of CHD deaths attributed to SCD. International guidelines specific to CHD patients and indications for primary prevention ICD are limited, and improving the risk stratification process is desperately needed. Cardiopulmonary exercise testing (CPET) provides a well-established marker of cardiopulmonary function in children and adults with CHD and has not been mentioned in 2015 and 2020 guidelines as a tool for SCD risk stratification. The aim of this study was to evaluate measurements obtained during CPET as predictors for the occurrence of severe arrhythmias during a three-year follow-up. The study design was that of a single-centre retrospective analysis of patients with complex CHD (univentricular heart, Ebstein’s anomaly, tetralogy of Fallot, truncus arteriosus communis, and transposition of the great arteries post arterial switch operation or Senning/Mustard procedure) undergoing CPET between 2009 and 2014. A symptom-limited customized ramped upright bicycle CPET protocol was used until exhaustion (respiratory exchange ratio > 1.0). The highest 30-second interval of oxygen uptake during exercise was defined as peak oxygen uptake (VO2peak). Data collected on the date of CPET were demographics (age, gender, body mass index), VO2peak, anaerobic threshold (VO2at), ventilatory efficiency (VE/VCO2 slope), respiratory exchange ratio at peak exercise, and pulse oximetric saturation at peak exercise (SpO2max). Medical charts and available Holter recordings, ICD-, pacemaker- and event-recorder readings were reviewed within a follow-up time of three years after CPET. Systemic ventricular function by transthoracic echocardiography was added to the analysis if assessed within 12 months of the index CPET.  Primary endpoint was survival without severe arrhythmia events (SAE), chiefly SCD, aborted SCD, appropriate ICD discharge, ICD anti-tachycardia pacing for VT, hospital admission for acute ventricular arrhythmia, cardiac syncope caused by ventricular arrhythmia, and the occurrence of non-sustained VT on Holter, event-recorder, pacemaker, or ICD recordings. Data analyses were performed using SPSS with appropriate statistical considerations. Univariate and backwards stepwise multivariable logistic regression models were used to identify parameters associated with SAE within three years. Time-to-event analysis was conducted via univariable and backwards stepwise multivariable Cox regression analysis. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic ability of VO2peak to predict SAE. In total, 1194 patients (663 male) were included in the study. Median age was 25.9 years (IQR 17.4–34.6 years), median BMI was 22.4 (IQR 19.8–25.6) kg/m2. Underlying diagnosis was: Univentricular heart (UVH) in 205 Ebstein’s anomaly (EBS) in 135 Tetralogy of Fallot (TOF) in 469 Truncus arteriosus communis (TAC) in 51 Transposition of the great arteries, arterial switch operation (TGA ASO) in 149 Transposition of the great arteries, Senning/Mustard procedure (TGA SM) in 185. Transthoracic echocardiogram was available in 1148 patients. Peak performance was reached by 1075 patients during CPET. Three years of follow-up were completed in 1101 patients (92.2 %). Holter recordings were available in 445 patients (38.1 %). During follow-up, ICD’s were present in 42 patients, 145 patients had a pacemaker, and event-recorders were used in three patients; of these totals, 27 pacemakers and 17 ICDs were implanted during follow-up, including five ICD-upgrades to preexisting pacemakers. Twenty-seven patients (2.3 %) died during follow-up: SCD diagnosed in 2 patients Non-SCD in 16 Unclear cause of death in 9. Severe arrhythmic events occurred in 97 of 1194 patients (8.1 %), with no statistically significant differences found between the distinct anatomical groups. Non-sustained VT was the most frequent SAE, while sustained VT was documented in eight patients  (Table 2, below): Clinical variables associated with SAE in multivariable analysis were age at CPET (OR, 1.029; 95 % CI, 1.00901.049; p=0.004) and VO2peak (OR, 0.951; 95 % CI, 0.921-0.982; p=0.002). VE/VCO2 slope, RERmax, SpO2max, gender, and type of CHD did not correlate significantly in the logistic regression model. ROC curve analysis identified VO2peak (AUC, 0.687; 95 % CI, 0.631-0.743; p < 0.001) and age (AUC, 0.659; 95 % CI, 0.602-0.715; p < 0.001) as independent predictors for SAE in CHD patients, with potential cut-off values for VO2peak at 24.9 ml/min/mg (Youden’s Index, 0.318; sensitivity 0.702; specificity 0.616) and age at 26.2 years (YI, 0.242; sensitivity 0.711; specificity 0.531). Lower VO2peak values in the second and first quartiles were associated with a decrease in SAE-free survival (90.7% and 82.2%). Patients with VO2peak above the cut-off value of 24.9 ml/min/kg presented with more frequent 3-year survival without SAE than patients with lower VO2peak than cut-off (95.8% vs. 85.1%). Age above the cutoff value of 26.2 years led to less frequent 3-year survival without SAE (87.4% vs. 95.1%).

Fluid challenge and balloon occlusion testing in patients with atrial septal defects. D'Alto M, Constantine A, Chessa M, Santoro G, Gaio G, Giordano M, Romeo E, Argiento P, Wacker J, D'Aiello AF, Sarubbi B, Russo MG, Naeije R, Golino P, Dimopoulos K. Heart. 2022 May 12;108(11):848-854. doi: 10.1136/heartjnl-2021-319676. PMID: 34413090   Take Home Points Left ventricular filling pressure determination pre closure of atrial septal defects (ASD) is a recommendation by ESC trans-catheter closure guideline Fluid challenge (0.9% saline, 7 ml/kg over 10 minutes) and ASD balloon occlusion testing showed smaller increase in pulmonary blood flow and decrease in shunt fraction in patients with higher (≥ 2 Wood Units) vs lower pulmonary vascular resistance Small rises in PVR ≥2 WU may carry significant implications with regard to cardiovascular hemodynamics in patients with ASD and fluid challenge may aid complementary information to LV diastolic disease, however larger studies and data standardization regarding cut off values is needed Commentary from Dr. Shailendra Upadhyay (Connecticut, USA), section editor of ACHD Journal Watch: Background: ASD closure may pose challenges in elevated pulmonary vascular resistance (PVR) with persistence of pulmonary vascular disease and in elevated left ventricular filling with resulting pulmonary edema after. European Society of Cardiology (ESC) guidelines advise measurement of left atrial (LA) or pulmonary arterial wedge pressure (PAWP) before and after balloon occlusion, however, guidance regarding the interpretation of these data is lacking. Fluid challenge has been utilized in PH centers to unmask LV disease. The study aimed to investigate the hemodynamic effects of fluid challenge or balloon occlusion, impact of mildly elevated PVR in patients selected for percutaneous ASD closure.   METHODS: Prospective multicenter study at three centers in Italy (January 2018 - December 2020). Inclusion criteria included cases referred for percutaneous secundum ASD closure, Qp:Qs>1.5. Hemodynamic data collections included: right atrial pressure (RAP), systolic, diastolic and mean pulmonary arterial pressure (mPAP), LA/PAWP, Qp:Qs and Fick cardiac output. PVR and SVR were reported in Wood Units (WU). Fluid Challenge: volume loading with infusion of 0.9% sodium chloride of 7 mL/kg over 10 min. Balloon occlusion involved temporarily closing the ASD with a sizing balloon. Measurements were taken at 4 points as noted in figure 1. Of the patients 88% underwent percutaneous ASD closure, 3 (6%) fenestrated ASD closure and 3 (6%) were untreated. Echocardiogram assessment of PH and diastolic function was performed at follow-up.     Results: N=50, mean age 46 years, 72% females. Individuals with Individuals with a PVR ≥2 WU at baseline hemodynamic assessment (higher PVR group) were older [mean 58 vs 42 years]   Fluid Challenge: After fluid challenge, statistically changes in hemodynamics were noted including a small increase in PAWP, the difference between PAWP and RAP, mean PAP increased by an average of 3 mmHg despite an open ASD. QP and Qs both increased but Qp had a more substantial elevation [2L/min], thereby increasing the Qp:Qs modestly [0.1] i.e. more left to right shunting and small reductions in PVR and SVR.   Patients with higher baseline PVR, findings included smaller Qp increase, greater mPAP increase and significant difference in change in PVR. Qp:Qs remained > 1.5 in low PVR group and in nearly all (90%) with elevated PVR, Qp:Qs dropped below 1.5.     Parameters with fluid loading and PVR ≤2 WU PVR ≥2 WU Comment Qp ↑↑ ↑ Qs ↑ ↑↑ Qp:Qs > 1.5 Yes No Dropped below 1.5 mPAP ↑ ↑↑ PAWP/RAP ↑ ↑ Not statistically significant PVR ↓ ↓ Not statistically significant SVR ↓ ↓↓ Balloon Occlusion test with and without concurrent fluid challenge testing:       Combined fluid challenge and balloon occlusion had similar effects on RAP, PAWP, PVR and mPAP in the higher and lower PVR groups, whereas there was a more pronounced reduction in SVR in the higher PVR group associated with a greater increase in PVR/SVR (p=0.0003 and p=0.026, respectively). At a mean follow-up of 27 months, all patients were alive, none developed signs of PH or diastolic dysfunction on follow-up echocardiogram.   CONCLUSIONS: ASDs with PVR <5 are deemed suitable for repair per ESC guidelines However, a significant difference in hemodynamics was detected between patients with a PVR ≥2 and ≤2 WU, at baseline and after fluid challenge and balloon occlusion. Patients with a higher baseline PVR were older and more often symptomatic, with significantly lower baseline Qp and shunt fraction, but with similar PAWP and had smaller Qp:Qs after fluid bolus. ASDs may mask LV diastolic dysfunction by acting as a relief valve While balloon occlusion has a role in this setting, authors suggest that fluid challenge has a complementary role in unmasking latent diastolic dysfunction, which may not be obvious after balloon occlusion alone. Fluid challenge can also test the ability of the pulmonary vascular bed to increase Qp, and may provide information on the resistance and compliance of the pulmonary circulation. This study suggests that even modest rises in PVR ≥2 WU may carry significant implications with regard to cardiovascular hemodynamics in patients with ASD. Fluid challenge may provide complementary information to balloon occlusion in this setting, but further studies are needed to standardise this approach and establish robust cut-offs to define LV disease, which current guidelines suggest should influence management.    

Diverse Right Ventricular Remodeling Evaluated by MRI and Prognosis in Eisenmenger Syndrome With Different Shunt Locations. Gong C, He S, Chen X, Wang L, Guo J, He J, Yin L, Chen C, Han Y, Chen Y. J Magn Reson Imaging. 2022 May;55(5):1478-1488. doi: 10.1002/jmri.27791. Epub 2021 Jun 21. PMID: 34152058   Take Home Points Eisenmenger syndrome patients with pre-tricuspid shunts show worse right ventricular decompensation remodelling features on MRI and have worse prognosis than those with post-tricuspid lesions.   Commentary from Dr Simon MacDonald (London, UK): Eisenmenger syndrome (ES) is a type of pulmonary hypertension in congenital heart disease where paradoxical right-left shunting occurs with associated systemic cyanosis with multiorgan complications. How the right ventricle remodels in this process and what this entails for prognosis has been unclear.   Chao Gong and colleagues investigated right ventricular (RV) remodelling with MRI in patients with different Eisenmenger syndrome (ES) subgroups classified by location of shunt. It was a single centre prospective study of 54 ES patients, 16 with pre-tricuspid and 38 with post tricuspid shunts. Patients with atrial septal defects (ASDs) and/or anomalous pulmonary venous drainage were classified as pre-tricuspid with those with ventricular septal defect (VSD) and/or patent ductus arteriosus (PDA) as post-tricuspid. Fourteen pre-tricuspid patients had ASDs only, with the largest post-tricuspid group being VSD only (19 of 38) with 11 having PDAs only.   MRI investigations detailed RV morphology, systolic function, RV-pulmonary artery (RV-PA) coupling and fibrosis, measured via gadolinium enhancement. They were also able to compare this to right heart catheterization data, and examined all-cause mortality or readmission for heart failure as clinical endpoints.   The pre-tricuspid patients were significantly older than post-tricuspid (43 vs 34 years, p=0.02), as a possible confounder, and 66% of patients were female. Blinding to shunt position and patient group during MRI analysis will not have been possible. Demographic data were as shown in Table 1 below:     Patients with pre-tricuspid shunts had lower mean PA pressures and pulmonary vascular resistance at catheterisation but greater pulmonary than systemic blood flows than those with post-tricuspid lesions.   MRI added additional information, not just on shunt location, but ventricular function and size, scar (assumed from gadolinium enhancement) and RV-PA decoupling, RV-PA decoupling being defined as the ratio of RV stroke volume to end-diastolic volume. The authors found that those with pre-tricuspid lesions had larger RVs, RV/LV volume ratios, worse RV function and RV-PA decoupling and this also correlated with worse outcomes. Myocardial tissue characterisation was possible, the authors finding that pre-tricuspid lesion patients had higher extracellular volumes, T1 values, and fibrosis as detailed in tables 3 and 4 below:     Sharing of volume load between LV and RV may explain why these patients do better than those with idiopathic PAH. LV volumes or shunts may not have been large enough to impact RV function in the post-tricuspid group. Numbers were not large enough for lesion specific subanalysis.   This study adds to previous studies that describe adverse RV remodelling using echo, now using MRI techniques, and also compares MRI findings to invasive haemodynamic data. The mismatch in PAH severity measured invasively and RV function may mean these additional measures that can be assessed on MRI will be increasingly useful, adding to the utility of cardiac MRI in this group of patients.   

Magnetic resonance lymphangiography in post-Fontan palliation patients with MR non-conditional cardiac electronic devices: An institutional experience. Ramirez-Suarez KI, Otero HJ, Biko DM, Dori Y, Smith CL, Feudtner C, White AM.Clin Imaging. 2022 Jun;86:43-52. doi: 10.1016/j.clinimag.2022.02.016. Epub 2022 Feb 23.PMID: 35334301   Take Home Points: The use of MRI, when no comparable alternative diagnostic imaging modality exist, as in the case of lymphatic system imaging, can be used with no major adverse effects in patients with previous epicardial lead Further studies are required in larger cohorts to elucidate safety measures more definitively Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch:   MRI remains the diagnostic modality of choice for the diagnosis of complex lymphatic disorders. Though modern pacemakers are MRI conditional, older pacing devices and other implantable electronic devices have still pose a theoretical restriction to MRI. Epicardial leads, often used in pediatric patients, have traditionally been included in this group with a relative contraindication to MRI due to the theoretical risk of cardiac excitation or thermal injury. The potential harm is attributed to a potential interaction between static and time-varying magnetic fields and device components with the consequences (theoretical) of local tissue damage, ventricular arrhythmias and device malfunction. It is however noted that in clinical practice, the retained leads are short and do not usually form conducting loops.   This study gives the perspective of a single center of 5 patients with complex CHD (post-Fontan) with MRI ‘incompatible’ devices in whom a Dynamic Contrast Enhanced MR Lymphangiography (DCMRL) was performed. The patients underwent DCMRL of the chest, abdomen and pelvis on a 1.5 Tesla Siemens system, under general anaesthesia. All patients had been discussed in an MDT (which included the family and an ethics team) and the risks/benefits explained to the patients.   In all 5 patients, there were no MR safety related adverse events occurring during or following the imaging. This shows potential safety however larger studies would be needed to define the safe practice measures more definitively.   An example of a case is shown below:     

Hypertensive response to exercise in adult patients with repaired aortic coarctation. Meijs TA, Muller SA, Minderhoud SCS, de Winter RJ, Mulder BJM, van Melle JP, Hoendermis ES, van Dijk APJ, Zuithoff NPA, Krings GJ, Doevendans PA, Spiering W, Witsenburg M, Roos-Hesselink JW, van den Bosch AE, Bouma BJ, Voskuil M.Heart. 2022 Jun 24;108(14):1121-1128. doi: 10.1136/heartjnl-2021-320333.PMID: 34987066   Take Home Points: Study involved use of Dutch registry CONCOR Exercise induced hypertension occurred in 44% of patients in this cohort of 675 patients Increased peak exercise systolic blood pressures (> 210 mmHg systolic) was found more often in males, and those with higher resting blood pressures Increased peak exercise systolic blood pressures were found less frequently in patients with bicuspid aortic valve and those following coarctation stenting Increased peak systolic blood pressures predicted higher resting systolic blood pressures in follow up, regardless of resting systolic blood pressure at rest baseline There was no correlation between the occurrence of later cardiovascular events (coronary artery disease, stroke, aortic complications, death) and peak exercise systolic blood pressure Commentary from Dr. Thomas Zellers (Dallas, USA), section editor of Congenital Heart Disease Interventions and ACHD Journal Watch: The authors sought to determine the prevalence of hypertensive response to exercise, identify factors associated with exercise induced hypertension and examine the association between peak exercise systolic blood pressure and resting systolic blood pressure and cardiovascular events at follow up.   The authors used the Dutch national congenital corvitia (CONCOR) registry and examine 920 patients with repaired coarctation. Of these, 675 patients (median age 24 years with range of 16-72 years) underwent exercise testing and follow up at a mean of 10.1 years. Variables examined included resting and stress blood pressure response to exercise, 24 hour ambulatory blood pressure monitoring, echo evaluation for LV hypertrophy and mass, and history of cardiovascular events.   Of the 675 patients, 44% showed a hypertensive response to exercise (systolic BP of > 210 mmHg for men and > 190 mmHg for women). Of the 299 patients with normal resting blood pressure, 35% (n = 104) had hypertensive response to exercise; 50% of those had hypertension at later follow up visits. Of the 376 with resting hypertension, 52% had a hypertensive response to exercise.   In evaluating factors associated with peak exercise systolic blood pressure (SBP), in multivariable analysis, increased resting SBP at baseline was positively correlated with increased peak exercise SBP. Males were also more likely to have elevated peak exercise SBP. Bicuspid aortic valve and coarctation stenting were negatively correlated with peak exercise SBP.   Peak exercise SBP positively predicted office SBP at follow up visit and increased ambulatory blood pressure measurements at follow up; this was independent of resting SBP at baseline. Resting SBP at baseline and the use of antihypertensive medications were also positive predictors of office resting SBP at follow up. When considering only normotensive patients at baseline, peak exercise SBP was also predictive of SBP at office follow up. Given that 35% of normotensive patients, at baseline, had exercise induced hypertension, and that 50% of those had resting hypertension at follow up, it appears that exercise testing, even in normotensive patients, can help predict systolic hypertension at follow up. This is a population that may require an increased frequency in follow up visits to address new onset of hypertension. However, of particular interest, hypertensive response to exercise did not correlate with adverse cardiovascular events.   One must realize that this is a multicenter study using a registry and thus there may be differences in who gets tested, which exercise protocols are used, the use of antihypertensive medications, and the follow up duration. This was a young cohort and thus, the incidence of cardiovascular adverse events may not yet have been realized at follow up.   

Exercise invasive hemodynamics in adults post-Fontan: A novel tool in understanding functional limitation and liver disease. Miranda WR, Jain CC, Borlaug BA, Connolly HM, Egbe AC.J Heart Lung Transplant. 2022 Jun;41(6):704-707. doi: 10.1016/j.healun.2022.02.023. Epub 2022 Mar 9.PMID: 35400586   Take Home Points: In the vast majority of patients with a Fontan circulation, the exercise capacity is significantly reduced due to a multitude of reasons, including impaired stroke volume augmentation, chronotropic incompetence, abnormal oxygen extraction by the muscles, lung disease and others. While obtaining resting hemodynamics in patients with a Fontan circulation is informative and can be helpful in guiding clinical decision making, it provides little information on patient’s hemodynamics during exercise. In this small study, the investigators describe their experience with four exercise hemodynamic studies obtained in patients with a Fontan circulation using supine bicycle. Three of these patients were referred for heart transplantation evaluation and the fourth for assessment of a Fontan pathway obstruction. Commentary from Dr. Yonatan Buber (Seattle, USA), section editor of ACHD Journal Watch:   Table: Clinical and hemodynamic data of the 4 study patients   The authors describe how in each of the cases, the invasively measured hemodynamics assisted in the clinical decision making: in Case 1, a case that was used I a combination with echo, it revealed increase in the wedge pressures due to severe systemic AV valve stenosis and the patient underwent a valvular intervention, in Case 2 it revealed significant diastolic dysfunction and elevation in the wedge pressures, and the patient was referred for a transplant evaluation, in Case 3, no marked abnormalities were found and the patients was referred to a rehab program and prescribed with a PDE-5 inhibitor with marked symptomatic improvement, and in Case 4, a significant increase in the IVC pressures was observed, indicating hemodynamically significant obstruction in the IVC limb, and stenting was undertaken with resolution of the gradient.   Invasive exercise hemodynamics in patients with a Fontan circulation provides an excellent method to evaluate the degree and the potential contributors to exercise intolerance, which as noted above is common in this patient population and may often be multi-factorial. In this brief and very educating communication, the authors provided with three examples of different hemodynamic abnormalities that were almost not apparent at rest and were revealed during exercise, and nicely show how this affected clinical decision making. Importantly, they also provide one example of a relatively benign hemodynamic response to exercise which prompted a referral to cardiac rehabilitation and initiation of a pulmonary vasodilator. No complications were reported in this series. Future directions include the utility of evaluating the effects of pre-exercise NO administration on exercise hemodynamics in Fontan patients, and the potential utility of less invasive methods such as combined cardio-pulmonary exercise testing with echo +/- non-invasive stroke volume assessment to provide with similar results and clinical implications.  

Cardiac MRI predictors of adverse outcomes in adults with a systemic right ventricle. Lewis MJ, Van Dissel A, Kochav J, DiLorenzo MP, Ginns J, Zemer-Wassercug N, Groenink M, Mulder B, Rosenbaum M.ESC Heart Fail. 2022 Apr;9(2):834-841. doi: 10.1002/ehf2.13745. Epub 2022 Jan 20.PMID: 35048545   Take Home Points: Cardiac MRI parameters may be used to predict increased risk of death, heart transplantation, or the need for a ventricular assist device in patients with a systemic right ventricle in biventricular physiology. A cut-off value of 130ml/m2 may be used to predict good survival outcomes. Commentary from Dr. MC Leong (Kuala Lumpur), section editor of ACHD Journal Watch: The systemic right ventricles (SRV) are inherently not meant for system circulation and will eventually fail. Assessing patients with SRV has been challenging, especially in identifying those who will fail early and require a heart transplant. Various methods have been advocated, such as (a) assessing the SRV function [1], (b) identifying myocardial fibrosis [2], and (c) assessing the left ventricular function [3]. This study looked at a novel way of assessing the SRV - by assessing the right ventricular dimension.   The study is a retrospective study, studying 158 patients from two centres with SRV and biventricular physiology i.e. congenitally corrected transposition of the great arteries (ccTGA) and transposition of the great arteries post atrial switch operation (DTGA). The right ventricular dimensions were acquired through magnetic resonance (MR) via conventional methods, and the right ventricular mass was calculated by including the interventricular septum. The MR-derived parameters were compared to the primary outcomes: a composite of death, heart transplantation referral, or destination therapy with a ventricular assist device. Table 1 shows the baseline characteristics of the cohort of patients. By and large, patients with ccTGA had a larger indexed right ventricular end-systolic volume, stroke volume, and a higher rate of primary outcomes.      21 patients (13%) met the primary endpoint over a cumulative follow-up of 1320 patient-years (median duration of follow-up: 8.5 years). 15 deaths (71%), 4 referrals for a heart transplant (20%), and 2 (10%) patients underwent destination VAD placement. The cause of death included 9 from progressive heart failure, 3 from sudden cardiac death, and 3 with an unknown cause. Univariable and multivariable predictors of the primary outcomes are tabulated in Table 2. Receiver operating curve analyses were performed to obtain cut-off values for predicting primary endpoints (Table 3).        For DTGA and ccTGA patients with ≥ moderate tricuspid valve regurgitation, the optimal cut-point of RVEDVI was higher when compared with patients with < moderate tricuspid valve regurgitation (DTGA: 141 vs.130 mL/m2; ccTGA: 131 vs. 124 mL/m2). However, for simplicity's sake, a cut-off value of 130ml/m2 was used and the value showed good survival estimates for both groups (Figures 1 & 2).        The emergence of multiple parameters to assess the systemic right ventricle proves that examining the SRV using a single parameter may yield inconsistent results. One such example is the right ventricular function. Many, if not all, of these patients, have varying degrees of tricuspid regurgitation. The degree of tricuspid valve regurgitation affects the accurate calculation of the systolic function of the right ventricle. The ventricular stroke volume contributes to tricuspid valve regurgitation and the true cardiac output. The ventricular function is often overestimated, especially in the presence of severe tricuspid regurgitation. Moving forward, should we be looking at a composite of parameters instead a single one?   References: Rutledge JM, Nihill MR, Fraser CD, Smith OE, McMahon CJ, Bezold LI. Outcome of 121 patients with congenitally corrected transposition of the great arteries. Pediatr Cardiol. 2002 Mar-Apr;23(2):137-45. Broberg CS, Valente AM, Huang J, Burchill LJ, Holt J, Van Woerkom R, Powell AJ, Pantely GA, Jerosch-Herold M. Myocardial fibrosis and its relation to adverse outcome in transposition of the great arteries with a systemic right ventricle. Int J Cardiol. 2018 Nov 15;271:60-65.  Surkova E, Segura T, Dimopoulos K, Bispo D, Flick C, West C, Babu-Narayan SV, Senior R, Gatzoulis MA, Li W. Systolic dysfunction of the subpulmonary left ventricle is associated with the severity of heart failure in patients with a systemic right ventricle. Int J Cardiol. 2021 Feb 1;324:66-71.  

Ebstein's Anomaly: From Fetus to Adult-Literature Review and Pathway for Patient Care. Ramcharan TKW, Goff DA, Greenleaf CE, Shebani SO, Salazar JD, Corno AF.Pediatr Cardiol. 2022 Apr 23. doi: 10.1007/s00246-022-02908-x. Online ahead of print.PMID: 35460366 Review. This review article aims to cover the pathophysiology of Ebstein’s anomaly including the varying severity and the associated structural, electrical and functional issues with thorough discussion of management. Throughout the article, sections are divided into fetal, neonatal, older children, adolescents and adults.   Commentary by Dr. Helen Parry (Leeds, UK), section editor of ACHD Journal Watch:   Introduction: This section sets out the aim of the review   Anatomical definition: The authors clearly state the hallmark of Ebstein’s anomaly is inferior displacement of the hinge-points of the septal and mural leaflets of the tricuspid valve into the right ventricle. This is due to failure of delamination of the leaflets and they usually form a combined leaflet. The valve annulus and functional orifice are rotationally displaced inferiorly to a varying extent.   Epidemiology and Etiology: 0.3-0.5% of congenital heart defects 40% of all tricuspid valve abnormalities   Associated abnormalities Structural Cardiac Abnormalities Pulmonary stenosis, up to and including pulmonary atresia Interatrial communication in >90%, +/- associated cyanosis Prominent Eustachian valve Tetralogy of Fallot Isolated ventricular septal defect Congenitally corrected transposition of the great arteries Abnormal left ventricle up to 39% (abnormal myocardial function, septal motion, non-compaction) RV fibrosis Mitral valve abnormalities Arrhythmia SVT, usually AVRT, accounts for 75% and is caused by a combination of discontinuity between the central fibrous body and septal atrioventricular ring and dilatation of the RA. There is a higher incidence of ventricular arrhythmia following surgery, possible due to ventriculotomy scar. Extracardiac associations These are mainly due to the space taken up by the dilated right heart and hypoperfusion of other organs Genetics Very few cases of Ebstein’s anomaly are inherited.   Presentation Fetal Detection depends on severity The most severe forms are associated with early in utero death Neonatal Only the more severe forms present this early, generally developing cyanosis and heart failure in the first few days of life. Whilst the PDA is open and pulmonary vascular pressures are high, the small RV may not be able to generate high enough pressures to open the pulmonary valve, creating functional pulmonary atresia. Closure of the PDA can both improve and worsen symptoms Adolescent/ Adult Presentations include: Incidental murmur Palpitations (40% from adolescence) Chest X ray done for another reason Cyanosis, particularly on exercise Older adults may present with cyanosis due to increased stiffness of the RV and bi-directional shunting across the ASD. They may also present with heart failure. Older patients with Ebstein’s anomaly may struggle during exercise due to: Inability to increase the RV output Further dilatation of the right heart due to increased systemic venous return, further displacing the septum and reducing LV function Increased right to left shunt Natural History Neonatal presentation 18% babies die in the first 28 days of life, 30% die before age 10 years and median mortality is 20 years Late effects include right heart failure, LV dysfunction, arrhythmia, endocarditis   Diagnostic Investigations The mainstay of fetal investigation is fetal echocardiography Post natally (some of these investigations are obviously only appropriate in older children and adults): ECG CXR TTE TOE Holter monitor +/- cardiac catheter Cardiac MRI CPET EPS Particular focus is given to the degree of apical displacement of the septal leaflet. >=15mm in children and >=20mm in adults is diagnostic. The Great Ormond Street Equation based on RA to LV+LA+RV ratio is also referred to but the clinical significance is not clear Similarly, the Carpentier classification is detailed Holter monitors may be particularly useful in picking up pre-excitation. The 70 year risk of sudden cardiac death is 15%. MRI may be useful in patients with poor echo windows and is the gold standard for right heart volumes.   Management Indications for surgery include Critically ill symptomatic neonates despite intensive medical management Severe or progressive cyanosis Progressive right heart dilatation Congestive heart failure Deteriorating systolic function RV outflow tract obstruction Decreasing or severe limitation (NYHA 3-4) Paradoxical embolus Recurrent or intractable life-threatening arrhythmia Specific comments about different age groups: Fetal- Some institutions advocate increased surveillance after 32 weeks Neonates- Generally improve as pulmonary vascular resistance drops Surgical management has higher mortality in neonates than any other age group. Careful assessment for univentricular or biventricular repair should attempt biventricular repair if possible Infancy- Anti-arrhythmic dugs as needed Surgical approach (see below) Adolescence and adults- Anti-arrhythmic therapy, consideration of ICD Cardiac catheterisation may be beneficial for evaluation of pulmonary vascular resistance pre operatively, or for device closure of the ASD Surgery in adolescents and adults: Guidance suggests indicated for more than moderate TR and symptoms, including deterioration in CPET performance, asymptomatic but progressive RV dilatation, dysfunction or progressive cardiomegaly on chest radiograph. Cardiac transplantation should be considered where there is no other good surgical option or severely impaired LV function.   Surgical techniques: Detailed discussion of techniques including more historical approaches is given. However, most centres would veer towards cone repair. The anterior and posterior leaflets are delaminated and the posterior leaflet free edge is rotated clockwise and sutured to the anterior leaflet free edge to create a new annulus. The atrialised RV was plicated and the new annulus constructed at the true morphological level. It is believed that this reduces the recurrence of TR. Outcomes of the cone repair show significant reduction in regurgitation, reduction in |RV size and lower mortality but with deterioration in RV function, due to the haemodynamics involved rather than deterioration being caused by the cone procedure. ASD closure is advocated but a fenestrated closure is favoured with small RV cavity/ poor RV function and high PVR. Glenn procedures may also be done at the time of repair to reduce preload on the poorly contracting RV allowing an aggressive repair strategy. This is described as a “one and a half” ventricle repair. Univentricular repair by over-sewing the tricuspid valve (Starnes) is not generally done outside the neonatal period. Surgical ablation of accessory pathways and medical management of arrhythmia/ prevention of post op arrhythmia is also discussed.   Pregnancy This section is short, mentioning fetal growth restriction in cyanosed women with up to 6% offspring having a form of congenital heart disease. Otherwise, pregnancy is well tolerated.   Conclusion This is more a brief summing up statement than a conclusion   Positive aspects: The section on associated cardiac abnormalities is excellent, particularly comprehensive. The article usefully highlights the risk of sudden cardiac death due to arrhythmia   Less positive aspects There is a clear description of classification systems used to assess severity but no detail of how this guides us clinically (See GOS equation and Carpentier grading) The cone repair is explained without the use of diagrams, making it extremely difficult to visualise The difficulty of assessing RV function when it is flattered by TR is not highlighted  

Long-term Outcomes of Adults With Tricuspid Regurgitation Following Transcatheter Atrial Septal Defect Closure. Bach Y, Abrahamyan L, Lee DS, Dharma C, Day J, Parker JD, Benson L, Osten M, Horlick E.Can J Cardiol. 2022 Mar;38(3):330-337. doi: 10.1016/j.cjca.2021.12.012. Epub 2021 Dec 30.PMID: 34974138   Take Home Points: In patients undergoing transcatheter secundum ASD closure, the pre-procedural presence of moderate or greater tricuspid regurgitation is associated with higher rates of all-cause mortality, hospitalization for either heart failure or atrial fibrillation, and new-onset heart failure and atrial fibrillation Exploratory analysis is suggestive of similar outcomes in a smaller subset of patients with persisting moderate or greater tricuspid regurgitation (as compared to those with reduction in tricuspid regurgitation severity to mild or less) following ASD closure Patients with persistent significant tricuspid regurgitation post ASD closure may need closer surveillance in their long-term follow up to allow earlier identification of cardiac morbidity and appropriate intervention to reduce mortality. Commentary by Dr. Timothy (Melbourne, Australia), section editor of ACHD Journal Watch: The presence of moderate to severe tricuspid regurgitation (TR) has been reported in 27 – 55 % of patients with ostium secundum atrial septal defect at the time of transcatheter ASD closure. Post-closure cardiovascular adverse event rates have been reported to be significantly higher in such patients after up to 45 months follow-up. This study aimed to compare the impact of moderate to severe TR on short and long-term outcomes following ASD closure, and to compare long-term outcomes between patients with postprocedural improved and persistent TR.   A retrospective single-centre cohort study of consecutive adult patients undergoing transcatheter ASD closure between 1998 and 2016 was performed at Toronto General Hospital. Exclusion criteria included the presence of additional left-to-right sided cardiac shunts, Ebstein anomaly, previous tricuspid valve surgery, and those without a baseline echocardiography report. Two patient groups were defined according to the presence of (1) mild or no TR (< moderate TR) and (2) moderate, moderate to severe, or severe TR (≥ moderate TR). Patients with baseline ≥ moderate TR were further stratified to either improved or persistent TR groups post-procedure.   Data from electronic medical records and paper charts were reviewed. Echocardiographic images were reassessed by a cardiac sonographer for evaluation of interobserver variability in TR grade. Follow-up period for acute outcomes was 30 days commencing the day of index discharge.   Appropriate statistical methodology was employed using SAS statistical software.   Figure 1 (below) outlines the patient cohort included in the study. Mean patient age was 48 ± 16 years, and 69% were female. The group with ≥ moderate TR were significantly older and more likely to present with a history of AF, HT, coronary disease, hypertension, diabetes, pulmonary hypertension, and COPD.     No difference in acute procedural or short-term (30 day) outcomes was observed between groups. Median follow-up for the 949 patients was 10.9 years. Unadjusted analysis found significantly higher all-cause mortality and new onset or hospitalization for heart failure/atrial fibrillation in the ≥ moderate TR group, while rates of cardiac surgeries or interventions were low and similar in both groups. After adjusting for age, sex, AF, coronary disease, heart failure, hypertension, diabetes, COPD, and Charlson comorbidity index, patients with baseline ≥ moderate TR continued to have a higher risk of all-cause mortality (adjusted hazard ratio 1.69, 95 % confidence interval 1.08-2.62; P = 0.02).     In the smaller subset of patients analysed for improved vs. persistent TR post ASD closure (n = 119), 61 % had improved to mild or less TR on follow-up echocardiography (median follow-up of 4 months, IQR 3-20 months), while the remaining 39% had persistent (≥ moderate) TR. The unadjusted exploratory analysis found patients with persistent TR to have significantly higher rates of new-onset heart failure, new-onset AF, composite hospitalisations for HF or AF, and overall mortality than patients with improved TR. Unadjusted cumulative incidence of all-cause mortality in the persistent TR cohort was also significantly higher than the improved TR cohort (P = 0.003). Due to the small sample size, adjusted survival analyses were not performed.   Data from this study complements other studies in regard to morbidity and mortality, as well as the degree of reduction in TR severity following ASD closure. There are a number of limitations, including the retrospective nature, small cohort included in the exploratory evaluation of long-term outcomes, and the non-standardised and early timing of post-procedure TR assessment. Nonetheless the findings place a spotlight on tricuspid regurgitation and the potential need for closer surveillance of those with persistent TR following transcatheter ASD closure.

Impact of Right Ventricular Pressure Load After Repair of Tetralogy of Fallot. Latus H, Stammermann J, Voges I, Waschulzik B, Gutberlet M, Diller GP, Schranz D, Ewert P, Beerbaum P, Kühne T, Sarikouch S; German Competence Network for Congenital Heart Defects Investigators *.J Am Heart Assoc. 2022 Apr 5;11(7):e022694. doi: 10.1161/JAHA.121.022694. Epub 2022 Mar 18.PMID: 35301850   Commentary from Dr. Thomas Zellers (Dallas, USA), section editor of Congenital Heart Disease Interventions and ACHD Journal Watch: Introduction and summary: The aim of the study was to assess the hemodynamic impact and prognostic relevance of RV pressure load in a population of patients following tetralogy of Fallot repair. Patients were older than 8 years of age at the time of evaluation with a CMR, echo and exercise stress test. There was no evaluation with initial post-operative RVOT gradient nor was there longitudinal hemodynamic evaluation. There was follow up information on adverse events (ventricular tachycardia or death) and pulmonary valve replacement. Below is the study population algorithm:     Results: Two hundred and ninety-six patients had complete data. Peak RVOT gradients were positively correlated with a) smaller RV volumes b) less pulmonary regurgitation c) lower RV and LV longitudinal systolic strain by echo and d) lower early diastolic strain rates by echo. A trend toward reduced exercise capacity was also found. Using univariable Cox regression analysis, the authors looked at prognostic relevance of RVOT gradients on the primary endpoints of death (n=6), sustained VT (n=2) and non-sustained VT (n=11). Higher RVOT gradients were significantly associated with these combined primary endpoints. Other predictors are shown in Table 2 below. Further, a RVOT peak gradient > 25 mmHg was associated with a > 3-fold increase in adverse cardiovascular events (HR 3.69, P=0.005) as seen in Figure 3. A second univariable Cox proportional hazard analysis that considered only death or sustained VT as showed a significant relationship with those two endpoints. A comparison between patients with RVOT peak gradients < 25     mmHg vs > 25 mmHg, revealed a much higher risk for these two endpoints in patients with higher gradients (HR 17.9, p= 0.007). A separate subgroup analysis looking at peak gradient and degree of PR was conducted. Peak gradients > 25 mmHg and moderate PR (not severe PR) also had a significant increase in combined adverse events. Bivariable testing was then performed to determine a relationship between peak RVOT gradients and the other parameters found to be significantly associated with primary outcome metrics on univariable analysis. These are outlined below in Table 3.     The authors also looked at an association between RVOT gradient and pulmonary valve replacement (PVR). This analysis was conducted in 292 of the 296 eligible patients. Pulmonary valve replacement was performed in 119 (41%) of the patients at a median of 3 years (0.1-12.3 yrs) after CMR evaluation. Using univariable Cox regression analysis, higher RVOT gradients were associated with a need for PVR. Other significant factors include type of palliation (valve sparing vs transannular patch), NYHA class > 1, increased RV volumes and mass, severity of PR and lower RVEF and LVEF. The authors further assessed the effects of mild (< 15 mmHg), moderate (15-30 mmHg) and severe (> 30 mmHg) RVOT gradients and degrees of PR (< 25% and > 25%) on the need for PVR. Patients with < 25% PR and RVOT gradients < 30 mmHg had the lowest risk for PVR (Figure 4 below).   Limitations: Overall, this is an interesting study that looks at the effect of peak gradient and pulmonary regurgitation on endpoints of death, non-sustained VT and sustained VT as well as need for pulmonary valve replacement and provides some insight into risk factors. However, there was no longitudinal and long term follow up from the surgical procedure with regard to these variables.        

Incidence, Risk Factors, and Outcomes of Atrial Arrhythmias in Adult Patients With Atrioventricular Septal Defect. Jacquemart E, Bessière F, Combes N, Ladouceur M, Iserin L, Gardey K, Henaine R, Dulac A, Cohen S, Belli E, Jannot AS, Chevalier P, Ly R, Clavier S, Legendre A, Petit J, Maltret A, Di Filippo S, Hascoët S, Marijon E, Waldmann V.JACC Clin Electrophysiol. 2022 Mar;8(3):331-340. doi: 10.1016/j.jacep.2021.09.004. Epub 2021 Oct 27.PMID: 35331427   Take Home Points Retrospective analysis of 391 patients diagnosed with AVSD (61% women) from 3 French centres (2001-2020). 22% of the cohort had trisomy 21. (Table 1) 85% of the cohort had undergone reparative surgery. A relatively small proportion (n=58, 15%) of the cohort were born with a complete AVSD (100% repaired). Mean age at enrolment 36.3 ± 16.3 years and mean duration of follow up 17 years after surgical repair. One quarter of patients (n=98) developed at least 1 atrial arrhythmia at a mean age of 39 years old. Lifetime risks for developing atrial arrhythmia to ages 20, 40, 60 years were 3.7%, 17.8% and 55.3 respectively. The commonest arrhythmia until the age of 45 years was IART/Focal atrial tachyarrhythmia. At beyond 45 years old, AF was the commonest arrhythmia. Independent risks associated with developing atrial arrhythmias were age; number of cardiac operations; left or right atrial dilation and moderate or severe left AV valve regurgitation (Figure 1). Those patients experiencing atrial arrhythmias had a higher subsequent risk of needing a pacemaker (42% vs 9%; P<0.001) ; developing heart failure (25% vs 1%; P<0.001) and experiencing a stroke (11% vs 3%; P=0.007). Commentary by Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch: Patients born with an AVSD are commonly seen in the ACHD clinic – AVSD comprises 7% of all congenital cardiac lesions. Most patients fare well following their surgical repair but there are a number of important issues for the team to watch for over time – mostly these relate to monitoring of valvar regurgitation and possibly stenosis (usually the left valve) and the surveillance of/treatment of atrial arrhythmias or progressive AV block. This analysis is welcomed to help guide and inform the ACHD team and their patients about what chronic risk is posed by atrial arrhythmias to patients with AVSD – mostly those whom have undergone surgical repair. The characteristics of the study cohort are seen in Table 1. It is not documented what antiarrhythmic therapies patients were receiving during their follow up and if this may have adjusted outcomes.   Table 1   Atrial arrhythmias Over a mean FU of 17.3 ± 14.2 years after first surgical repair, one quarter of patients (n=98) presented with at least one episode of atrial arrhythmia (Figure 1). Until the age of 45 years, IART/FAT was the commonest arrhythmia. After the age of 45 years old, AF was commoner. At the end of follow up, approximately three quarters of patients (n=75, 77%) with a history of experiencing atrial arrhythmias subsequently had persistent or permanent atrial arrhythmia. Table 2 shows risk factors for developing atrial arrhythmia. The prevalence of atrial arrhythmia in different phenotypic subgroups is shown in Figure 2.   Table 2 – Risk factors for development of atrial arrhythmias   Figure 1   Figure 2     Limitations It is unclear from the data presented how many patients underwent ablation for atrial arrhythmias during follow up and how this modified their outcomes. It is unclear from the data presented what medical treatments patients received and how this may have modified outcomes. Conclusions Atrial arrhythmias occur frequently in patients with AVSD with over half experiencing such phenomena by the age of 60 years old. Whilst it is important to understand risks for developing atrial arrhythmias, further research is needed to understand how they could be optimally prevented. It would be insightful to understand how medical therapy (i.e. antiarrhythmics) and upfront ablative intervention helps to modify long term outcomes.   

Nationwide Registry-Based Analysis of Infective Endocarditis Risk After Pulmonary Valve Replacement. Stammnitz C, Huscher D, Bauer UMM, Urban A, Nordmeyer J, Schubert S, Photiadis J, Berger F, Klaassen S; German Competence Network for Congenital Heart Defects Investigators.J Am Heart Assoc. 2022 Mar;11(5):e022231. doi: 10.1161/JAHA.121.022231. Epub 2022 Feb 18.PMID: 35179045   Take Home Points: Bovine jugular vein valves (Contegra/Melody) have the highest risk of infective endocarditis, irrespective of the mode of deployment (surgical or percutaneous) Male sex and higher number of previous pulmonary valve replacements increase risk of Infective Endocarditis Commentary from Dr. Shailendra Upadhyay (Connecticut, USA), section editor of ACHD Journal Watch: This study is the largest retrospective analysis of the German NR-CHD (National Register for Congenital Heart Defects) comparing the risk of infectious endocarditis (IE) after percutaneous pulmonary valve implantation or surgical pulmonary valve replacement in congenital heart disease. All patients with CHD with at least 1 surgical pulmonary valve replacement (SPVR) or percutaneous pulmonary valve replacement (PPVI) before January 1, 2018 [January 2007-Dec 2017] were included and followed up for the combined end point (grafts infected or explanted, or the patient was deceased). The study included 1170 patients (median age 12, 5-20 years, 56% males, 68% < 18 years) that included 1598 surgical pulmonary valve replacement (SPVR) including - aortic/pulmonary homograft, heterograft including Contegra, bio-prosthetic valved conduits using Bovine/Porcine materials, mechanical valves and percutaneous pulmonary valve implantation (PPVR) including Melody and Edward Sapien valves. Diagnoses included: Tetralogy of Fallot (TOF)- commonest, Truncus Arteriosus, Aortic stenosis and s/p Ross operation. Total follow-up was 9397 years (per patient median 10 years). Clinical characteristics of patients is noted in table 2. IE occurred in 4.8% during a 10-year median follow-up (6-10 years), tables 1 and 2. IE After homograft 1.3%; IE After heterograft 4.3% [Heterograft non Contegra 2.5% and Contegra 5.4%]; IE After Melody 7.5%.     IE showed no significance influence on the overall survival of the patients ([HR], 3.57; P=0.20). Bovine jugular vein valves (Contegra and Melody) had the highest risk of IE [Table S4], irrespective of the mode of deployment, either surgical or percutaneous. In the multivariable analysis, the risk of IE was increased in the male sex, in patients with a higher number of previous pulmonary valve replacement and for bovine jugular vein valves (with a similar risk for Melody versus Contegra valves). [Table 3].     Conclusion: Homograft or non Contegra heterograft replacement has the least risk of IE. Bovine jugular valves (Contegra/Melody) have the highest risk of IE whether deployed surgically or percutaneously. Male sex and higher number of previous PVR add significant IE risk. Other significant risk factors for IE are male sex and higher numbers of previous PVR. The Edwards-Sapien valve may be useful for PPVI in high risk subgroups for IE, however data are limited.

Young adults after arterial switch operation for transposition of the great arteries in Switzerland: a growing population. Ruperti-Repilado FJ, Affolter J, Bouchardy J, Gabriel H, Stämpfli SF, Engel R, Schwerzmann M, Greutmann M, Tobler D.Swiss Med Wkly. 2022 Feb 23;152:w30114. doi: 10.4414/smw.2022.w30114. eCollection 2022 Feb 14.PMID: 35230031   Take Home Points: Patients with d- transposition of the great arteries (d-TGA) post arterial switch generally have a good biventricular function and a normal exercise capacity. Some of these patients suffer from cardiac events or require reinterventions, and they are likely patients with complex d-TGA. Pregnancy within this cohort is largely safe with favourable outcomes. Commentary from Dr. MC Leong (Kuala Lumpur), section editor of ACHD Journal Watch: Previous studies have reported the long-term outcomes of patients with d-transposition of the great arteries (d-TGA) after the arterial switch operations (1-4). These studies, which were retrospective in nature, were usually flawed with issues inherent in retrospective studies, e.g., missing data, patients lost to follow up and recall errors. In this study, the authors attempted to overcome these deficiencies by examining data prospectively. Data were extracted from a prospectively collected Swiss Adult Congenital HEart disease Registry (SACHER). The registry was established in 2013 and was webbed-based (5). In this study, the authors examined the outcomes of patients with d-TGA post arterial switch operation in the hope of raising awareness among general practitioners and general cardiologists regarding this growing population and their potential complications.   All 149 patients with d-TGA post arterial switch in the registry were included. Baseline characteristics of the cohort were tabulated in Table 2. In the study, the authors echoed the findings of previous studies, which demonstrated that adults post arterial switch operation generally presented with good biventricular function and normal exercise capacity. However, many had residual lesions, which may or may not require intervention. The usual residua of RVOT obstruction, branch pulmonary artery stenoses, infective endocarditis and etc., were largely similarly to those seen in previous reports. The study also touched on the functional status (VO2max and NT-proBNP) as well as pregnancy outcomes which were largely unremarkable.   Interestingly. the authors showed that patients with complex d-TGA tended to suffer from cardiac events (occurring in 18% of patients with complex d-TGA) and required reintervention (Figure 1). These patients also had a trend towards a lower survival compared to their peers with simple TGA but the difference was not statically significant. The authors argued that this might be due to the overall low number of outcomes. Of the outcome examined by the study, one that particularly interested me was the growth of neo-aortic root and the accompanying neo-aortic valve incompetency. Admittedly, the reported aortic dissection in this population is exceedingly low. However, the study showed that the majority of the patients had at least moderate dilatation of the aortic root, and they demonstrated a marginal but progressive growth in the aortic dimensions over time (Table 2 & S2). Whether many of these patients would eventually require intervention in the distant future is yet to be seen. Only time will tell. Equally interesting was the presence of the increase in the QRS duration over time (Table S2). Its significance is yet to be determined, but one would assume that a progressive increase in the QRS duration may lead to inter-ventricular dyssynchrony, which may cause deterioration of heart function in the long run.   All in all, this is an interesting audit of the Swiss d-TGA cohort. The authors should be commended for establishing the prospectively collected SACHER registry. It would give systematically collected outcome data regarding this cohort of patients in the distant future and help understand this unique cohort. We would wait with much eagerness for the long-term effects of neo-aortic root dilatation as well as the prolonged QRS as they unfold over time. Reference: Tobler D, Williams WG, Jegatheeswaran A, Van Arsdell GS, McCrindle BW, Greutmann M, Oechslin EN, Silversides CK. Cardiac outcomes in young adult survivors of the arterial switch operation for transposition of the great arteries. J Am Coll Cardiol. 2010 Jun 29;56(1):58-64. Khairy P, Clair M, Fernandes SM, Blume ED, Powell AJ, Newburger JW, Landzberg MJ, Mayer JE Jr. Cardiovascular outcomes after the arterial switch operation for D-transposition of the great arteries. Circulation. 2013 Jan 22;127(3):331-9. Santens B, Van De Bruaene A, De Meester P, Gewillig M, Troost E, Claus P, Bogaert J, Budts W. Outcome of arterial switch operation for transposition of the great arteries. A 35-year follow-up study. Int J Cardiol. 2020 Oct 1;316:94-100. Kempny A, Wustmann K, Borgia F, Dimopoulos K, Uebing A, Li W, Chen SS, Piorkowski A, Radley-Smith R, Yacoub MH, Gatzoulis MA, Shore DF, Swan L, Diller GP. Outcome in adult patients after arterial switch operation for transposition of the great arteries. Int J Cardiol. 2013 Sep 10;167(6):2588-93. Tobler D, Schwerzmann M, Bouchardy J, Engel R, Stambach D, Attenhofer Jost C, et al.; On Behalf Of Sacher. Swiss Adult Congenital HEart disease Registry (SACHER) - rationale, design and first results. Swiss Med Wkly. 2017 Oct;147:w14519   

Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis. Venet M, Jalal Z, Ly R, Malekzadeh-Milani S, Hascoët S, Fournier E, Ovaert C, Casalta AC, Karsenty C, Baruteau AE, Le Gloan L, Selegny M, Douchin S, Bouvaist H, Belaroussi Y, Camou F, Tlili G, Thambo JB. JACC Cardiovasc Imaging. 2022 Feb;15(2):299-308. doi: 10.1016/j.jcmg.2021.07.015. Epub 2021 Sep 15. PMID: 453863   Study Summary and Take-Home Points: In this retrospective study that included 66 patients with suspected endocarditis of a prosthetic pulmonary valve or right sided conduit, 44 patients had definite diagnosis of endocarditis, 10 had possible and 12 a rejected diagnosis. The most frequent pathogens were staphylococcus and streptococcus, both accounting for 68% of overall microbiological findings. The median interval between the initial endocarditis suspicion date and a 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18 F-FDG-PET/CT) was 7.5 days. Appropriate antibiotics were started before PET/CT for 83.3% of the patients. Among them, the median delay between antibiotics onset and PET/CT was 7 days. Sufficient myocardial suppression was obtained in 92.5% of the cases. The sensitivity, specificity, positive, and negative predictive values of 18F-FDG PET/CT for diagnosis of PPVE were as follows: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%), respectively. The median time between antibiotics starting and PET/CT in the false negative cases was 2.5 days and median CRP level was 56 mg/L, whereas in true positive cases, this delay was 7.0 days and median CRP level was 67.0 mg/L. More atypical causing bacteria were grown in the false negative group. The type of prosthesis was not associated with higher false positives or negatives PET/CT results. Among the 44 cases of definite endocarditis, 27 patients exhibited both positive imaging studies (i.e. TTE/TEE or cardiac CT) and PET/CT, and 13 patients presented a positive PET/CT despite a negative imaging study. PET/CT appeared to provide better diagnostic capabilities when more common causing organisms were involved: when streptococcus or staphylococcus were identified as the causative agent, 80% PET/CTs were positive, whereas when less common microorganisms were involved, PET/CT was positive in 66.7%. Notably, four definite endocarditis patients had both negative PET/CT and imaging studies. In these patients, the causing organisms were atypical (Streptococcus sanguinis, Aggregatibacter actinomycetemcomitans, Candida parapsilosis, and Coxiella burnetii) Embolic and distant lesions were identified by PET/CT in 31 patients. Pulmonary septic emboli were identified by chest CT and PET/CT in 14 patients, 13 of which had definite and 1 had possible endocarditis. During a median follow up period of 26.6 months in the endocarditis group, 75% of the patients required surgery and one 50 year old patient with tetralogy of Fallot and other “severe comorbidities” passed away from the infection. Commentary from Dr. Yonatan Buber (Seattle, USA), section editor of ACHD Journal Watch: The overall incidence of endocarditis in congenital heart disease patients is estimated at 1.33 per 1,000 person-years, and 50% to 60% of the cases involve right-sided valves with a high proportion of pulmonary prosthetic valve or conduit endocarditis. Both transcatheter and surgically implanted valve can be affected. Although the integration of 18F-FDG positron emission PET/CT increased the diagnostic sensitivity by 52%-70% to 91%-97% for endocarditis involving left-sided valve, the data on its applicability for right-sided on endocarditis remains limited.   This was a retrospective study conducted between 2010-2020 in 8 centers in France aimed to evaluate the diagnostic performance of 18F-FDG PET/CT in the diagnosis of prosthetic pulmonary valve or conduit endocarditis in CHD patients. Sixty-six suspected pulmonary prosthetic valve or conduit endocarditis episodes involving 59 patients were included, all of which underwent an 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18F-FDG PET/CT) study . Median age was 23.4 years, 10 patients were below 15 years of age, the youngest was 5 years old, and 72.7% were men. The involved RVOT prosthetic substrates included percutaneous pulmonary valved stents (Melody, Medtronic Inc; and Sapien, Edwards Lifesciences devices), surgical pulmonary bioprostheses, right ventricle to pulmonary artery prosthetic conduits, and pulmonary homografts.   Similar to other studies reporting the diagnostic performance of 18F-FDG-PET/CT in left-sided endocarditis, the main strength appears to be its strong positive predictive value, which in this study was 92%, whereas its main limitation remains the very low negative predictive value, which in this study was only 47%. Sensitivity (79%) and specificity (72%) were in the moderate-high range. Noteworthy observations that are of considerable clinical implications are that the diagnostic capabilities of 18F-FDG-PET/CT were lower when the causative organisms were atypical, when the inflammatory markers were lower and when the studies were performed <3 months from the time of the valve or conduit implantation.   The authors provide additional theoretical explanations to the low negative predictive performance, including the fact that many nuclear physicians are less familiar with RVOT features than left-sided valve prostheses, and the potential lower difference between pathological and nonpathological 18F-FDG uptake with some biological tissues such as bovine jugular vein materials or pulmonary homografts.   Notably, the gold standard used for the diagnosis of endocarditis in this study was an expert consensus obtained by an endocarditis group, while only 4 explanted valves or conduits showed evidence of infection. An important limitation is the lack of intracardiac echo studies in this series, a tool that is commonly used in contemporary practice for suspected pulmonary valve endocarditis patients.   18-F FDG PET/CT can thus be a useful tool in the workup of patients with suspected prosthetic pulmonary valve endocarditis. It appears that is should be performed early in the inflammation phase but not in the first 2-3 months after the valve implantation, and that CRP levels could help guide the timing. Negative results should not be used to rule out the diagnosis of endocarditis in this clinical setting.   

Baffle Complications in Adults After Atrial Switch for Transposition of the Great Arteries. Woudstra OI, Alban FTE, Bijvoet GP, de Bruin-Bon RHACM, Planken RN, Leiner T, Boekholdt SM, Warmerdam EG, Sieswerda GT, Mulder BJM, Bouma BJ, Meijboom FJ.Can J Cardiol. 2022 Jan;38(1):68-76. doi: 10.1016/j.cjca.2021.09.034. Epub 2021 Oct 9.PMID: 34634378   Take Home Points: There was a high incidence of baffle interventions for baffle complications in patients with a prior atrial switch operation for TGA These interventions were mainly for worsening symptoms (effort intolerance, fluid retention or desaturation) Combining contrast-enhanced transthoracic echocardiography with CT for screening, markedly increases the diagnostic yield of diagnosing baffle complications (CT found baffle stenosis in almost half) There was little correlation between clinical signs and the presence of baffle complications on CT Pulse-wave Doppler had a low sensitivity to detect systemic venous baffle stenosis Baffle stenosis was associated with lower peak exercise work rates (obstruction to ventricular filling in stiff baffles are clinically relevant) Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch: Baffle complications remain a rather overlooked subset of late complications following atrial switch operations for TGA. Interventions for baffle complications have been done for both baffle leaks and baffle stenosis in symptomatic patients. The use of percutaneous intervention for asymptomatic patients is also increasing. The scope of these complications is poorly studied and it’s diagnosis on conventional transthoracic echocardiography limited. For this reason, guidelines recommend routine interval screening by advanced imaging (CT/MRI). The prevalence on previous studies by these modalities on routine screening was 40-60% (though many study limitations noted in these cohorts). This dual-center study conducted in the Netherlands had 3 aims:   To assess the prevalence of consequences of major baffle-related complications (baffle interventions / strokes) To assess the prevalence of baffle stenoses and baffle leaks in unselected TGA patients after atrial switch surgeries To assess whether clinical signs and symptoms differed between patients with and without these complications. A cross-sectional imaging sub-study (2017-2019) of participants in the Dutch CONCOR registry (2001 onward) was done looking at a standardized screening protocol for baffle complications, instituted in both centers in 2017. All patients had a routine contrast-enhanced transthoracic echo with agitated saline during rest and exercise to assess baffle patency – agitated saline (after a test injection to exclude a large R-L shunt in case of a baffle leak) is performed using 8mL agitated saline and graded upon the amount of bubbles seen in the systemic ventricles within 3 cardiac cycles.   Since 2017, both centers involved in the study instituted CT (arterial and venous phase scanning) as part of routine screening. Systemic venous baffle dimensions were measured and stenosis was defined as a transverse luminal diameter <10mm.   There were 67 patients with arterial switch surgeries for TGA in the CONCOR Registry. Mustard repairs were done in 85% (n=57). Patients were followed up for a median of 9 years. Baffle interventions were performed in 36% (n=24), with 46% having re-interventions. Fourteen had their interventions prior to enrollment in the CONCOR registry with no details available. Most patients presented with increasing symptoms (effort intolerance, fluid retention or desaturation). Indications for intervention included:   1 – baffle leak only 6 – stenosis only 3 – both stenosis and leak No patients experienced strokes, 5 died (3 heart failure, 2 infective endocarditis) and 12 were lost to follow-up. Figure 3 below shows a cumulative risk of re-intervention for baffle complications as 25% at 15 year follow-up:     Fifty patients had CT scans. Of the 29 patients who had both contrast-enhanced transthoracic echo (CE-TTE) and CT, 4 (14%) had no baffle complications; 11 (38%) had baffle leaks only; 5 (17%) had stenosis only and 9 (31%) had both stenosis and leaks. Systemic venous to systemic arterial circulation (R-L) shunting was found in 69% (n=20) of patients – none of them had known or suspected shunting. In 8 patients (40%) the shunting was spontaneous without provocation. Both exercise and Valsalva maneuvers increased the diagnostic yield on CE-TTE.     There was no statistically significant associations between clinical characteristics (including oxygen saturation at rest or exercise) and the presence of baffle leaks.   Baffle stenosis was associated with a lower peak work rate noted on exercise echocardiography (89 ±24W vs 123±21W, p<0.001) – figure 5 below. This remained significant even after correcting for body surface area (p=0.003). Peak Doppler flow over the systemic venous baffle was not associated with the presence of anatomic stenosis (<10mm diameter) on CT (1.1 vs 1.0m/s for those with and without stenosis respectively; p=0.53).   

Cardiac MRI predictors of adverse outcomes in adults with a systemic right ventricle. Lewis MJ, Van Dissel A, Kochav J, DiLorenzo MP, Ginns J, Zemer-Wassercug N, Groenink M, Mulder B, Rosenbaum M.ESC Heart Fail. 2022 Apr;9(2):834-841. doi: 10.1002/ehf2.13745. Epub 2022 Jan 20.PMID: 35048545   Commentary by Dr. Helen Parry (Leeds, UK), section editor of ACHD Journal Watch:   Introduction: The anatomical right ventricle re-models in order to adapt to function as a systemic ventricle. However, a point is reached where this is maladaptive.   Study question: Do MRI measurements of the volume of the systemic right ventricle predict clinical course?   Method: This was a retrospective case-control study. Two centres were involved: the Columbia University Irving Medical Centre and the Amsterdam University Medical Centre.   Inclusion criteria for cases: Age >= 18 years Congenitally corrected transposition of the great vessels (CCTGA) D-TGA with mustard or Senning (atrial switch) Ability to safely undergo MRI scanning Three primary outcomes studied were death, referral for cardiac transplant and use of ventricular assist device. Degree of tricuspid regurgitation (TR) and medications were analysed. The MRI images were analysed by manual tracing in end diastole and end systole. The degree of inter rater variability was assessed by 2 reporters blindly analysing the same 10 scans. Receiver operating curves and area under the curve (AUC) were calculated for: Right ventricular end diastolic volume, indexed (RVEDVI) Right ventricular end systolic volume, indexed (RVESVI) Right ventricular ejection fraction, RVEF (RVEF= RVEDV-RVESV)/100) Right ventricular mass The AUCs were compared using Cox proportional hazard regression analysis using STATA. Adult patients with a systemic right ventricle who were unable to undergo MRI scanning due to presence of a non-MRI conditional device were used as controls.   Results: Baseline cardiac MRI scanning was performed between December 1999 and November 2020 on patients who met the inclusion criteria: 101 DTGA with atrial switch 57 CCTGA N=158 A total of 21 patients (13%) met the primary end point during a follow up period of 1320 patient years. Those with CCTGA were more likely to meet the endpoint (9% versus 21%, p= 0.029). There were 15 deaths, 4 referrals for cardiac transplant and 2 patients were given a ventricular assist device as destination therapy.   Patients with CCTGA and DTGA with atrial switch were analysed separately by univariable and multi variable analysis. Multivariable analysis was performed according to tricuspid regurgitation of moderate severity or more and age at MRI. Separate multivariable analysis was performed in patients with adjustment for tricuspid valve replacement following MRI. In all the above analyses, RVEDVI, RVESVI, RVEF and RV mass remained predictive of the primary end point at the 1 in 20 level (p<0.05). No association between the presence of tricuspid regurgitation of moderate severity or greater and the primary end points were found.   Thirty nine adult patients with systemic right ventricles had non-MRI conditional devices. Eight of these (21%) met the primary end point during follow up and there was no statistically significant difference with the MRI group.   Discussion and conclusion: MRI measurements outlined above predict end stage heart failure in patients with systemic right ventricles. This is superior to the use of estimated right ventricular function on 2D transthoracic echo alone when compared with the previous literature.   Positive aspects of the study: Two centres were used to increase confidence in findings Inter rater variability was very small Novel: this study is the first looking at RV size and function according to MRI assessment as predictors of outcome in systemic right ventricle Negative aspects: The sample size meant a relatively small number of patients met the primary end point, making the statistical power of the study questionable Patients with tricuspid regurgitation were divided into a) less than moderate and b) moderate or more. It may be that there is a significant difference between patients with moderate and patients with severe TR, especially since TR is so common in patients with systemic right ventricles. The clinical application requires further work. Knowing these patients are more likely to develop end stage heart failure does not necessarily mean interventions can be made at this point that would prevent that from happening.   

Pregnancy outcomes in women with a systemic right ventricle and transposition of the great arteries results from the ESC-EORP Registry of Pregnancy and Cardiac disease (ROPAC).   Tutarel O, Baris L, Budts W, Gamal Abd-El Aziz M, Liptai C, Majdalany D, Jovanova S, Frogoudaki A, Connolly HM, Johnson MR, Maggioni AP, Hall R, Roos-Hesselink JW; ROPAC Investigators Group. Heart. 2022 Jan;108(2):117-123. doi: 10.1136/heartjnl-2020-318685. Epub 2021 Apr 28. PMID: 33911009   Take Home Points In women with a systemic right ventricle (sRV) after atrial switch for transposition of the great arteries (121 patients) or congenitally corrected transposition of the great arteries (ccTGA, 41 patients), in this international prospective observational registry, pregnancy was well tolerated with favourable maternal and fetal outcomes with: 26 (21%) having at least 1 major adverse cardiac event (MACE) 16 (9.8%) having heart failure needing treatment 11 (6.8%) having arrthymia (5 atrial and 6 ventricular) needing treatment 4 (2.5%) having other events No deterioration in sRV was seen in those who had pre and post pregnancy echoes Prepregnancy signs of heart failure and sRV ejection fraction <40% predicted MACE.   Commentary by Dr. Simon MacDonald (London, UK), section editor of ACHD Journal Watch There is uncertainty about how a systemic right ventricle supports the systemic circulation and adapts to the volume changes seen in pregnancy. This is important in patients with transposition of the great arteries (TGA) who have had the atrial switch operation (Mustard or Senning operation) and those who have congenitally corrected transposition of the great arteries (ccTGA), this study helping inform management of pregnancy for these women.   They used an international, prospective, observational registry of pregnant patients with cardiac disease called the European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Registry on Pregnancy and Cardiac disease (ROPAC). They studied all pregnancies in women with a sRV enrolled in this database from January 2007 to January 2018. Baseline characteristics were collected before pregnancy, including echocardiography where available.   The primary combined endpoint taken was major adverse cardiac event (MACE), defined as maternal death, supraventricular or ventricular arrhythmias needing treatment, heart failure (requiring hospital admission, new or change in treatment), aortic dissection, endocarditis, ischaemic coronary event and other thromboembolic events.   5739 women were in the registry, 162 had a sRV (121 post atrial switch and 41 ccTGA). Baseline characteristics are shown in table 1:     Pregnancy outcomes were as in table 2:     Obstetric and fetal outcomes were as in table 3. 48.5% had a caesarean section and there was 1 fetal death in a woman with TGA, none in ccTGA women. There were no maternal deaths. 26 of the 79 women having a caesarean did so for cardiac reasons, such as reported heart failure (23%) or severity of cardiac disease (34%).     There were 34 premature births with 15 of these induced, 12 spontaneous and 7 unknown. This was not significantly associated with heart failure or NYHA class but was with maternal cardiac medication use (p=0.01). 17.1% of ccTGA women had low birthweight infants, 18.2% with TGA. Prepregnancy signs of heart failure, a RVEF <40% were predictors of MACE, being primigravida reduced the risk, as seen in figure 1:     The authors conclude that the majority of women with sRV tolerate pregnancy well with low rates of MACE and without maternal or neonatal mortality. This was a large prospective study, compared to previous smaller retrospective studies. Numbers were too small for multivariate analysis and obstetric and fetal complications seemed less than that reported in other smaller studies however. Serial echo data was only available on a limited number as a caution. The authors also note that most of the women studied had TGA with palliative Mustard or Senning operation. This will change as the arterial switch operation is the predominant operation now for this condition, with the left ventricle supporting the systemic circulation, and the proportion of woman with ccTGA and systemic right ventricle will proportionately increase.