Adult Congenital Heart Disease

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.