Adult Congenital Heart Disease

Identifying Risk Factors for Massive Right Ventricular Dilation in Patients With Repaired Tetralogy of Fallot Cochran CD, Yu S, Gakenheimer-Smith L, Lowery R, Lu JC, Mahani MG, Agarwal PP, Dorfman AL. Am J Cardiol. 2020 Mar 15;125(6):970-976. doi: 10.1016/j.amjcard.2019.12.016. Epub 2019 Dec 28. PMID: 31964501 Similar articles Select item 31918854   Take Home Points: In patients with rTOF, age at complete repair >6 months, longer QRS duration > 160 milliseconds, and non-Caucasian race were significantly associated with massive RV dilation by CMR. An age cutoff of 6 months is clinically relevant, proposed explanations include prolonged cyanosis or elevated RV pressure load leading to myocardial damage and subsequent dilation Non-Caucasian race was an unexpected and strong predictor of massive dilation. This finding could potentially contribute to an evolving understanding of inequality in outcomes and merits further investigation Earlier referral for CMR in the presence of these risk factors may be indicated.   Commentary from Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch:   Introduction: Surgical relief of RVOTO in TOF surgical repair results in pulmonary valve insufficiency and related long-term sequelae; therefore, pulmonary valve replacement (PVR) has been widely utilized to reduce RV volume overload, but optimal timing is unknown. Indexed right ventricular end-diastolic volume (RVEDVi) by CMR is a widely used predictor of poor outcomes and a subset of patients seem to have a propensity for rapid progression to severe RV dilation before initial CMR evaluation. This study aims to identify risk factors for massive RV dilation among rTOF patients presenting for their first CMR at a tertiary US institution.   Patients and Methods: A retrospective study, identified patients with a diagnosis of TOF who underwent their first CMR imaging study between October 2007 and March 2015. Inclusion criteria for the study were a diagnosis of TOF following complete surgical repair and first CMR performed post repair at their center. Exclusion criteria included PVR before first CMR, unknown date or type of initial repair, or lack of ventricular size measurements on CMR. Cases of massive RV dilation were defined as patients with an RVEDVi ≥200 ml/m2 measured by CMR. Controls consisted of patients within the same cohort with RVEDVi <200 ml/m2 on first CMR.   Results: A total of 387 patients with TOF were identified. A total of 39 cases were identified and matched to 73 controls. A flowchart depicting patient identification is shown in figure 1   Figure 1. Patient identification using CMR database. CMR = cardiac magnetic resonance; PVR = pulmonary valve replacement; RV = right ventricle; RVEDVi = indexed right ventricular end-diastolic volume; TOF = tetralogy of Fallot; rTOF = repaired tetralogy of Fallot   Median age at complete repair was 0.6 years (IQR 0.3 to 3.0 years). Transannular patch repair, a known risk for RV dilation was the most common type of repair followed by RV to pulmonary artery conduit placements, and finally, other repairs which included transatrial muscle bundle resection and ventricular septal defect closure without pulmonary artery patch. No non-transannular or “limited” transannular patches were identified as having a massive RV by our criteria. Less than half of our study cohort (46 patients, 41.1%) had total bypass time and/or cross-clamp times (45 patients, 40.2%) recorded in their surgical reports.   Three clinical factors were significant from univariate analysis: Non-Caucasian race, age at complete repair >6 months, and QRS duration. In multivariable analysis, all 3 factors, non-Caucasian race (AOR 7.84, p = 0.01), age at repair >6 months (AOR 2.90, p = 0.03), and QRS duration (AOR 1.03, p = 0.005) remained significant (Table 1).   Table 1:   Discussion: In patients with rTOF, age at complete repair >6 months, longer QRS duration, and non-Caucasian race were significantly associated with massive RV dilation at first CMR. In this population, 10% is unlikely to have their RV return to normal size after PVR. To our knowledge, this is the first study reporting these risk factors.   An age cutoff of 6 months is clinically relevant, as it is at the latter end of the typical range for primary repair of TOF. An exact mechanism for this risk factor is unclear. Proposed explanations include prolonged cyanosis or elevated RV pressure load leading to myocardial damage and subsequent dilation. RV dysfunction in the setting of chronic hypoxia has not been widely investigated. Furthermore, reoxygenation of chronically hypoxic hearts during and after cardiopulmonary bypass leads to myocardial reperfusion injury.   The QRS interval is a clinical measurement used in some guidelines as an indication for PVR. Preoperative QRS duration has previously been shown to be an indicator of postoperative RV size and functional recovery following valve replacement. Severe QRS prolongation (≥180 milliseconds) has been linked with ventricular tachycardia and sudden death. RV ejection fraction by CMR has been shown to negatively correlate with QRS duration. The mean QRS duration in this study (160 milliseconds) matches the cutoff used as a criterion for PVR in one highly-referenced publication.   Non-Caucasian race was an unexpected and strong predictor of massive dilation. Additional exploration into the causes of this finding was beyond the scope of this study. However, there is a small body of literature looking at racial and ethnic disparity in mortality following congenital heart surgery. This finding could potentially contribute to an evolving understanding of inequality in outcomes and merits further investigation.   Conclusion: Age > 6 months at complete repair, prolonged QRS duration, and non-Caucasian race are independently associated with a massively dilated RV (RVEDVi ≥200 ml/m2) at first CMR in our rTOF patients. Earlier referral for CMR in the presence of these risk factors may be indicated. The potential role of healthcare disparities in these findings requires further investigation.    

Tricuspid regurgitation severity after atrial septal defect closure or pulmonic valve replacement Martin-Garcia AC, Dimopoulos K, Boutsikou M, Martin-Garcia A, Kempny A, Alonso-Gonzalez R, Swan L, Uebing A, Babu-Narayan SV, Sanchez PL, Li W, Shore D, Gatzoulis MA. Heart. 2020 Mar;106(6):455-461. doi: 10.1136/heartjnl-2019-315287. Epub 2019 Aug 23. PMID: 31444268 Similar articles Select item 31589989   Take Home Points: RV volume-offloading procedures (ASD closure, PVR for pulmonic regurgitation) were associated with significant reductions in the severity of functional tricuspid regurgitation, in addition to a reduction in RV and RA size, irrespective of intervention on the tricuspid valve itself Most positive remodeling of the right heart was seen within 6 months of intervention Baseline right atrial size was predictive of persistent TR at 12 months on multivariate analysis.     Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch: Surgical and catheter interventions to reduce right ventricular (RV) volume overload are common in the ACHD population, including closure of atrial septal defects (ASD) and pulmonic valve replacement (PVR). However, the effect of RV volume reduction on pre-existing tricuspid regurgitation (TR) following ASD closure and PVR is largely unknown and thus indications for concomitant tricuspid valve (TV) surgery at the time of such procedures is largely at the discretion of the surgeon and ACHD team. The aim of this study was to examine the effect of interventions aimed at reducing RV volume overload on pre-existing TR, and the additional contribution of concomitant TV surgery.   Methods This was a single-centre retrospective study of patients treated between 2005 and 2014 at The Royal Brompton Hospital, London.   Inclusion criteria were: Secundum ASD, sinus venosus ASD, PAPVD or pulmonic regurgitation (moderate or severe). At least mild TR pre-operatively. Full echocardiographic study available at baseline and six- and twelve- months post index intervention. Exclusion criteria were: Primary TR due to malformed TV (e.g. Ebstein anomaly). Significant LV systolic or diastolic dysfunction due to myocardial or left-sided valvular disease. Cardiac lesions were categorized as secundum ASD, sinus venosus ASD, PAPVD, and pulmonic valve insufficiency after repair of TOF or PS. Two-dimensional echocardiographic measurements for RV function were performed offline, and included: RV basal, mid, and longitudinal dimensions from the apical 4-chamber view at end-diastole; RVFAC; end-systolic RV eccentricity index; RVOT dimensions at end-diastole; and RA/LA area ratio. TV regurgitant severity was measured using annulus diameter; systolic tenting area; coaptation distance; CW Doppler of the TR jet; and vena contracta width.   Results 162 patients met inclusion criteria and formed the study cohort. Mean age was 41 +/- 16 years, and 62 (38%) were male. 101 underwent repair of ASD/PAPVD (82 secundum ASD [50.6%)], 18 sinus venosus ASD (11.1%), and 1 PAPVD [0.6%]), while for PVR 56 (34.6%) had PR after TOF repair and 5 (1.9%) were following PS surgery.   Ninety-eight (60.5%) patients underwent surgery, and 64 (39.5%) catheter interventions. Overall, tricuspid repair was performed in 18 (11.1%) patients, by ring annuloplasty (10, 55.6%), suture annuloplasty (7, 38.9%) and leaflet suture without annuloplasty (1, 5.6%).   Changes in echocardiographic parameters at six and twelve months are shown below in Table 2 and figure 2:   Key changes six months after intervention included a significant reduction in TR severity in the overall cohort, tricuspid annulus diameter, systolic tenting area, coaptation distance, RV area, 2-D sizes, and right atrial area. Less change was seen at 12-month follow up. Those with moderate or severe TR 6 months after intervention had worse pre-operative functional class compared to those with less TR. No differences in RV size and function parameters was seen between those with and without residual TR after repair.   Reduction in TR severity was seen in both the ASD/PAVR and TOF/PS groups (figure 3) with no difference in residual TR between groups (5.9% vs. 8.2% respectively, P=0.75):     Reduction in TR was also seen after excluding those who underwent TV repair at the time of surgery (figure 4):     Risk factors for residual TR at 12 months on univariate analysis included age, pre-operative TR severity, tenting area, TAPSE, RA area, LA area, and septal E/e’. Only RA area remained in the model on multivariable logistic regression included all univariable correlates.   Conclusions   Severity of TR was reduced following RV volume-offloading procedures (ASD closure, PVR for pulmonic regurgitation), in addition to reduction in RV and RA size, irrespective of intervention on the tricuspid valve. Most positive remodeling of the right heart was seen within 6 months of intervention. Baseline right atrial size was predictive of persistent TR at 12 months on multivariate analysis.   The key limitation of this paper is the retrospective data. Nonetheless the sample size is strong for a congenital heart disease cohort, and reflective of the general ACHD population. The authors correctly warn against direct comparisons between those who underwent TV repair and those who did not given differences in baseline TR severity.   Further studies are required to better identify patients who should be offered TV surgery. In the meanwhile, decisions to intervene will likely continue to be made on a case-by-case basis by the cardiac surgeon and/or ACHD team.    

Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study. Maagaard M, Heiberg J, Redington AN, Hjortdal VE. Eur J Cardiothorac Surg. 2020 Mar 1;57(3):574-580. doi: 10.1093/ejcts/ezz278. PMID: 31625565 Similar articles Select item 31972544   Take Home Points: Patients with small, unrepaired ventricular septal defect (VSD) who are apparently well, do have physiological impairment. A reduction in systolic and isovolumetric acceleration and isovolumetric velocity at the left and right ventricular free wall and septum at rest and during exercise were noted in patients with small VSD compared to controls. The left ventricular isovolumetric acceleration is inversely correlated to the size of the shunt.     Commentary from Dr. M.C. Leong (Kuala Lumpur, Indonesia), section editor of ACHD Journal Watch: Patients with a small ventricular septal defect (VSD) and non-significant shunt were often perceived to be healthy. These small VSD were seen to be haemodynamically insignificant and hence do not bring any damage to health apart from the slight but negligible increase in the risk for infective endocarditis. However, recent studies have demonstrated their effect in limiting patient’s functional capacity. This study aimed to assess the effect of small, haemodynamic insignificant VSD’s on the cardiac contractility especially during exercise. Cardiac contractility was assessed via isovolumetric acceleration, a sensitive echocardiographic marker of cardiac contractility which is independent of the loading condition of the ventricles.   This is a case control study, involving 34 patients with insignificant VSD shunts (median shunt ratio on cardiac magnetic resonance flow assessment: 1.2) and 28 healthy individuals. At baseline, the two groups were found to be comparable in terms of age, body weight, heart rate and blood pressures. At rest, patients with small VSD’s were noted to have a lower isovolumetric acceleration (IVA) and isovolumetric velocity (IVV) at the left and right ventricular free wall as well as the septal wall (Table 2).   During exercise, patients with small VSD’s demonstrated a lower IVA, IVV and peak systolic velocity at the left and right ventricular free wall and septum compared to controls (Figure 1). On further analysis, left ventricular IVA was noted to be inversely correlated to the shunt size. Peak exercise capacity was positively correlated with right ventricular IVV and septal IVV but not the left ventricular IVV (Figure 2).       This study, albeit being a small one, provides insights to the non-benign nature of small, haemodynamically insignificant VSDs. The effect of small VSDs on cardiac contractility is present not only at rest but also during exercise. However, these findings have yet to translate into a recommendation for closure as a different study by the same group of authors showed lower peak systolic velocity and IVA in patients post VSD closure compared to controls during exercise (ref). This study showed that even after closure of the VSD, there was impairment of the ventricular contractility during exercise which suggests that the ventricular contractility does not improve with VSD closure. Long term outcome of these group of patients with small VSDs compared to normal controls would be interesting to note.    

Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome Chiriac A, Riley DC, Russell M, Moore JP, Padmanabhan D, Hodge DO, Spiegel MR, Vargas ER, Phillips SD, Ammash NM, Madhavan M, Asirvatham SJ, McLeod CJ. J Am Heart Assoc. 2020 Mar 17;9(6):e014554. doi: 10.1161/JAHA.119.014554. Epub 2020 Mar 15. PMID: 32174228 Free Article Similar articles Select item 32172648   Take Home Points: This is a large contemporary longitudinal study of Eisenmenger patients at 2 large US Academic centers Predictors of sudden cardiac death in this cohort were (on univariate analysis): Older age HR 1.03 LVEF <40% HR 3.38 Right Atrial Pressure > 10mmHg HR 2.49 Atrial fibrillation HR 6.36 Complete Heart block HR 27.49 QRS duration >120ms HR 2.34 Presence of a pacemaker HR 2.75 Advanced pulmonary hypertensive drugs – protective HR 0.21 On multivariate analysis, only AF and QRS duration >120ms remained as adverse predictors, the use of advanced pulmonary hypertensive drugs remained protective.     Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch: In patients with Eisenmenger syndrome, little is known about the risk factors for sudden cardiac death (SCD). Previously recognized predictors for all-cause mortality in this population included oxygen saturations, arrythmias and type of defect (pre-vs post-tricuspid). In this retrospective review, 2 tertiary centers in the USA followed up patients with Eisenmenger syndrome to help elucidate the predictive factors for SCD.   The review was conducted at The Mayo Adult Congenital Heart Disease Clinic and the Ahmanson/UCLA Adult Congenital Heart Disease Center for the period 1987 to 2015. A total of 246 patients were reviewed. Sixty-five percent were women and the mean age was 37.3 years. The median follow-up period was 7.1 years.   The defect distribution was as follows: ventricular septal defect (42%, n=104), atrial septal defect (24.4%, n=48 secundum, 11 sinus venosus, 1 coronary sinus ASD), PDA (12%, n=30). Atrioventricular canal defects were present in 17% (n=42), and 13% (n=32) had characteristics of single ventricle physiology. Of these patients, 15.4% (n=38) have in fact had a palliative procedure in the past. A total of 42 patients (17%) had Downs syndrome, with atrioventricular canal defects being the most common defect in this group.   Heart failure was seen in 42.3% of patients. Only 3.7% had documented coronary artery disease. Syncope was documented in 20 patients (8.1%). Nineteen patients were listed for transplant – 7 (3%) had received a combined heart/double lung transplant.   Two-hundred and eighteen patients had a systemic LV – with a mean LVEF of 52%. More than 60% of patients had RV enlargement and moderate to severe RV dysfunction was present in 55.3%. The RA pressure was elevated in 92 patients (49.7%). The estimated RVSP was >80mmHg in 83.4% of cases   Most patients were in sinus rhythm at first consultation, but many exhibited intermittent atrial arrythmias. After complete follow up, atrial fibrillation was noted in up to 16.7% (n=41) of patients. Both atrial and other supraventricular tachycardias were seen in an additional 20% of patients on follow-up. Only 3.7% had sustained ventricular arrythmias. Thirty percent of patients were on anti-arrhythmic drugs..   Thirteen patients had pacemakers (5.3%) – 7 epicardial and 6 transvenous systems. Four had intra-cardiac defibrillators (ICD’s). The indications for pacing were complete heart block, sinus node dysfunction, sinoatrial exit block. Anticoagulation was prescribed in 22.4% (n=55), mainly for atrial fibrillation or atrial flutter. Forty-three percent (n=105) were treated with advanced pulmonary hypertension therapies.     A total of 136 patients died during follow-up. In 40 patients (16.3%), the cause was sudden cardiac death (see figure 1 above). The patients with non-sudden cardiac death was mainly due to heart failure.     On univariate analysis – table 3 above, age (p<0.001), male sex (p=0.02), clinical heart failure (p<0.001) and atrial fibrillation at presentation (p=0.022) were significant independent predictors of total mortality. Advanced pulmonary hypertensive therapies were protective (p<0.001). Combined ASD and VSD was associated with a higher mortality (HR 4.34, 95% CI 1.72-10.95, p=0.002).     For sudden cardiac death, age (p=0.011) and atrial fibrillation (p<0.011) remain independent predictors. The presence of a pacemaker increases risk of SCD – HR 2.75 (95% CI 1.07 – 7.06). There was no association between type of anatomical defect and risk of SCD. Downs syndrome also did not confer increased risk (HR 1.24, p=0.582)   Once again, advanced therapies for pulmonary hypertension was strongly protective, reducing the risk 5-fold (HR 0.21, 95% CI 0.1-0.44, p<0.001).     Independent echo predictors of mortality for sudden cardiac death were: Reduced LVEF (<40% - for these the overall mortality was 83% - HR 3.38, 95%CI 1.71-6.66, p<0.001), increased RA pressure >10mmHg (HR 2.49, 95%CI 1.13-5.48, p=0.024), RV index for myocardial performance (RIMP)(HR 6.16, 95%CI 1.92-19.61, p=0.002).     Please refer to the table 6 above for the ECG predictors of sudden cardiac death: Atrial fibrillation (HR 6.35), Complete Heart block (HR 27.49), QRS duration >120ms (HR 2.34), Right atrial enlargement (HR 2.11), RBBB (HR 2.4). Arrythmia surveillance was not part of a protocol, and screening was done at the discretion of the attending clinician. There was no significant association between anti-arrhythmic medication use or ablation in the prevention of SCD – these numbers were small though so it’s unlikely that meaningful conclusions could be drawn.   The presence of a pacemaker was significantly associated with an increased risk of SCD (HR 2.75, 95%CI 1.07-7.06, p=0.036). Of the 13 with pacemakers, 5 had SCD. Those with a high ventricular pacing burden were more likely to suffer SCD compared to those with atrial only pacing.     On multivariate analysis, atrial fibrillation, QRS duration>120ms, and advanced therapies for pulmonary hypertension remained significant – Figure 3 above shows the survival curves for these 3 groups:   A: Atrial fibrillation (HR 11.45, p<0.0001) B: QRS duration >120ms (HR 2.51, p=0.0072) C: Advanced ongoing therapies for pulmonary hypertension conferred benefit (HR 0.14, p<0.0001)   This is obviously a retrospective review and subject to the same limitations and biases.