Adult Congenital Heart Disease Transplantation: Does Univentricle Physiology Impact Early Mortality?

BACKGROUND: With patients with congenital heart disease increasingly living into adulthood, there is a growing population of patients with adult congenital heart disease (ACHD) who have heart failure. Limited data exist on evaluating heart transplantation in this population. METHODS: A retrospective review was performed of patients with ACHD who underwent heart transplantation from November 1990 to January 2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those patients with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range [IQR]) or counts (%). RESULTS: A total of 77 patients with a median age of 36 years (IQR, 27-45 years) were identified, including 57 (74%) BiV and 20 (26%) UniV patients. Preoperatively, UniV patients were more likely to have cirrhosis (9 of 20 [45.0%] vs 4 of 57 [7.0%]; P < .001) and protein losing enteropathy (4 of 20 [20.0%] vs 1 of 57 [1.8%]; P = .015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs 13 [23%]; P = .04). Operative mortality was 6.5%, 2 of 20 (10%) among UniV patients and 2 of 57 (4%) among BiV patients (P = .276). Median clinical follow-up was 6.0 years (IQR, 1.4-13.1 years). Survival tended to be lower among UniV patients compared with BiV patients, particularly within the first year (P = .09), but it was similar for survivors beyond 1 year. At 5 years, the incidence of rejection was 28% (IQR, 17%-38%) and that of coronary allograft vasculopathy was 16% (IQR, 7%-24%). CONCLUSIONS: Underlying liver disease and the need for heart-liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV patients, particularly within the first year, but it was similar for survivors beyond 1 year.

PA-VSD Without MAPCA(s): Review of Long-Term Outcomes and Reinterventions.

BACKGROUND: Pulmonary atresia with ventricular septal defect without major aortopulmonary collateral arteries (MAPCAs) is an uncommon form of congenital heart disease. As more patients with congenital heart disease live to adulthood, the objective of this article was to review the long-term results of this specific population. METHODS: A review of the PubMed database was performed using pertinent key words (pulmonary atresia, tetralogy of Fallot, conduit, right ventricle-pulmonary artery) concentrating on studies from 1990-present and published in English. Most studies of pulmonary atresia-ventricular septal defect patients included those with and without MAPCAs. Analysis included examination of the entire cohort, consideration of the proportion of patients with MAPCAs, and any subgroup analysis of the patients without MAPCAs. RESULTS: Survival is approximately 80% at ten years and is improved with complete repair and larger pulmonary arteries. Some studies have found genetic syndromes and extracardiac anomalies to impact survival, while others have not. Incomplete repair has been shown to be associated with worse survival. Independent of initial management strategy, patients with pulmonary atresia and ventricular septal defects without MAPCAs require repeat intervention on the right ventricular outflow tract. Hypoplastic pulmonary arteries have been shown to be a risk factor for reintervention, and decreased conduit durability has been shown with younger age at implantation of conduit. CONCLUSIONS: Long-term outcomes have improved for patients with pulmonary atresia-ventricular septal defect without MAPCAs, with complete repair and adequate pulmonary arteries favorable for survival. Long-term outcomes include reinterventions, both catheter-based and surgical, predominantly on the right ventricular outflow tract.

Outcomes Following Multivalve Reoperation in Adults with Congenital Heart Disease: A 30-Year, Single Center Study.

OBJECTIVE: As patients with congenital heart disease (CHD) increasingly live into adulthood, reoperative surgery is frequently required. While half of these are valve-related procedures, little is known regarding early and late outcomes, and factors associated with adverse outcomes. METHODS: From 1993-2022, 1,960 adult CHD (ACHD) patients underwent repeat median sternotomy at our institution. Of these, 502 patients (26%) underwent intervention on ≥2 valves and constituted the study cohort. RESULTS: The median age was 39 (27, 51) years and 275 patients (55%) were females. A second sternotomy was performed in 265 patients (53%), third in 135 (27%), fourth in 75 (15%), and ≥fifth in 27 (5%). Interventions were performed on 2 valves in 436 patients (87%), 3 valves in 64 patients (12%), and 4 valves in 2 patients (1%). The most common combinations were pulmonary and tricuspid in 241 patients (48%), followed by mitral and tricuspid in 85 (17%), aortic and pulmonary in 42 (8%), and aortic and mitral in 41 (8%). Early mortality was 4.2% overall and 2.7% for elective operations. Non-elective operations and CHD of major complexity were independently associated with early mortality. Median follow-up was 14 years. One, 5-, and 10-year survival were 93.6%, 89.3%, and 79.5%, respectively. Factors independently associated with overall mortality were age, ventricular dysfunction, coronary artery disease, renal failure, double valve replacement, non-elective operations, and bypass time. CONCLUSIONS: Multiple valve interventions are common and confer low early mortality in the elective setting. Referral prior to ventricular dysfunction and in an elective setting optimizes outcomes.

Haemodynamic contributors to pulmonary hypertension across the spectrum of adult congenital heart disease.

AIMS: Adult congenital heart disease (ACHD) includes multiple disease states that predispose to pulmonary hypertension (PH). Haemodynamically, PH depends on abnormalities in three components: pulmonary blood flow (Qp), pulmonary vascular resistance (PVR) and pulmonary venous pressure (PVP). We sought to evaluate the prevalence and prognostic impact of individual haemodynamic abnormalities in ACHD. METHODS AND RESULTS: Retrospective study of ACHD patients undergoing cardiac catheterization at Mayo Clinic between 1999 and 2022 who were followed for the combined endpoint of death/heart transplantation. Among 1005 patients, 37% had mean pulmonary artery pressure (mPAP) ≥25 mmHg with more systemic ventricular disease, cyanotic disease and shunt lesions, highest N-terminal pro-B-type natriuretic peptide and worse right heart remodelling/dysfunction. Among those with biventricular circulation, elevated PVP, PVR and mPAP were associated with prognosis, but not increased Qp >8 L/min. However, risk of death/transplant increased for PVR only at ≥3 Wood units (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.17-4.15; p < 0.0001) and for mPAP only at ≥25 mmHg (HR 3.15, 95% CI 2.17-4.58; p < 0.0001), not at current recommended lower cutpoints. Combined abnormalities in PVP and PVR were associated with worst outcome (HR 5.20, 95% CI 3.55-7.63; p < 0.0001) with intermediate risk with either abnormality (HR 2.11, 95% CI 1.46-3.04; p < 0.0001). Findings were consistent across type of biventricular ACHD. Only with the Fontan (univentricular) circulation was a lower mPAP threshold (20 mmHg) associated with adverse outcomes. CONCLUSIONS: Elevation of mPAP ≥25 mmHg in ACHD with a biventricular circulation is prognostically important regardless of disease phenotype, but milder PH of 21-25 mmHg is not associated with adverse outcome unless associated with Fontan circulation. Elevation in PVP >15 mmHg and PVR ≥3 Wood units were each individually associated with mortality with combined abnormalities associated with greatest risk. Categorizing PH in ACHD by haemodynamic mechanism (PVR, PVP or Qp) allows meaningful prognostication, and may allow more unified study of targeted therapies across heterogeneous disease states in ACHD.

Outcomes of Esophageal Varices in Adults With Fontan Palliation and Liver Cirrhosis.

Background: The purpose of this study was to define the risk and outcomes of esophageal varices in adults with Fontan palliation and liver cirrhosis undergoing esophagogastroduodenoscopy (EGD). Method: The results of EGD, abdominal ultrasound, and liver biopsy, as well as clinic notes from the hepatologist, were reviewed to determine the diagnosis of cirrhosis and esophageal varices. The incidence of acute gastrointestinal bleeding complication was assessed among patients with esophageal varices using the time of EGD as the baseline. Results: Of 149 patients with Fontan palliation and liver cirrhosis, the prevalence of esophageal varices at baseline EGD was 34% (51 of 149). Of 98 patients without esophageal varices at baseline EGD, 27 (27%) underwent subsequent EGD, of whom 11 showed a new diagnosis of esophageal varices. The incidence of a new diagnosis of esophageal varices was 9% per year. Of 62 patients with esophageal varices, 9 (15%) had acute gastrointestinal bleeding complications during 45 (37-62) months of follow-up, yielding an incidence of 5% per year. Of the 9 patients, 8 underwent EGD and variceal banding during the hospitalization for bleeding and 1 patient died of septicaemia. Of the 8 patients who survived to hospital discharge, 2 patients were readmitted for esophageal bleeding within 12 months from the index hospitalization. Higher hepatic vein wedge pressure and hepatic vein pressure gradient were associated with esophageal varices and bleeding complications. Conclusions: In this selected sample of adults with Fontan palliation and liver cirrhosis, esophageal varices were relatively common, and patients with esophageal varices had risk of bleeding complications.

Contexte: Cette étude visait à déterminer le risque de varices œsophagiennes et leur issue clinique chez les adultes ayant fait l'objet d'une intervention de Fontan et présentant une cirrhose hépatique chez qui une œsophagogastroduodénoscopie (OGD) a été réalisée. Méthodologie: Les résultats de l'OGD, de l'échographie abdominale et de la biopsie du foie, ainsi que les notes cliniques de l'hépatologue ont été consultés pour établir les diagnostics de cirrhose et de varices œsophagiennes. L'incidence des complications hémorragiques gastro-intestinales aiguës a été évaluée chez les patients présentant des varices œsophagiennes en utilisant l'OGD initiale comme référence de départ. Résultats: Chez les 149 patients ayant fait l'objet d'une intervention de Fontan et présentant une cirrhose hépatique, la prévalence des varices œsophagiennes lors de l'OGD initiale était de 34 % (51/149). Parmi les 98 patients sans varices œsophagiennes lors de l'OGD initiale, 27 (27 %) ont subi une OGD ultérieure, et 11 d'entre eux ont alors reçu un diagnostic de varices œsophagiennes. Le taux d'incidence des nouveaux diagnostics de varices œsophagiennes était de 9 % par année. Sur les 62 patients présentant des varices œsophagiennes, 9 (15 %) ont subi des complications hémorragiques gastro-intestinales aiguës au cours d'une période de suivi de 45 (37 à 62) mois, ce qui correspond à un taux d'incidence de 5 % par année. Huit des 9 patients ont subi une OGD et une ligature des varices par bande élastique durant leur hospitalisation en raison des complications hémorragiques, et un patient est décédé des suites d'une septicémie. Deux des 8 patients en vie au moment du congé de l'hôpital ont été réhospitalisés pour une hémorragie de l'œsophage dans les 12 mois suivant la première hospitalisation. Une pression d'occlusion plus élevée de la veine hépatique ainsi qu'un plus grand gradient de pression de la veine hépatique ont été associés à la survenue de varices œsophagiennes et de complications hémorragiques. Conclusions: Dans cet échantillon d'adultes ayant fait l'objet d'une intervention de Fontan et présentant une cirrhose hépatique, la fréquence des varices œsophagiennes était relativement élevée, et les patients présentant des varices œsophagiennes étaient exposés à un risque de complications hémorragiques.

Cardiac remodelling during pregnancy in women with congenital heart disease and systemic left ventricle.

AIMS: Women with congenital heart disease (CHD) are at risk of pregnancy-related adverse outcomes (PRAO). The purpose of this study was to assess temporal changes in cardiac structure and function (cardiac remodelling) during pregnancy, and the association with PRAO in women with CHD. METHODS AND RESULTS: Retrospective study of pregnant women with CHD and serial echocardiograms (2003-2021). Cardiac structure and function were assessed at pre-specified time points: prepregnancy, early pregnancy, late pregnancy, and postnatal period. PRAO was defined as the composite of maternal cardiovascular, obstetric, and neonatal complications. The study comprised 81 women with CHD (age, 29 ± 5 years). Compared to the baseline echocardiogram, there was a relative increase in right ventricular systolic pressure (RVSP) (relative change 13 ± 5%, P < 0.001, in early pregnancy; and 18 ± 5%, P < 0.001, in late pregnancy). There was a relative decrease in right ventricle free wall strain (RVFWS) (relative change -11 ± 3%, P < 0.001, in late pregnancy; and -11 ± 4%, P = 0.003, in postnatal period), and a relative decrease in RVFWS/RVSP (relative change, -10 ± 5%, P = 0.02 in early pregnancy, -26 ± 7%, P < 0.001, in late pregnancy, and -14 ± 5%, P < 0.001, in postnatal period). Baseline right ventricular to pulmonary arterial (RV-PA) coupling, and temporal change in RV-PA coupling were associated with PRAO, after adjustment for maternal age and severity of cardiovascular disease. CONCLUSION: Women with CHD had a temporal decrease in RV systolic function and RV-PA coupling, and these changes were associated with PRAO. Further studies are required to delineate the aetiology of deterioration in RV-PA coupling during pregnancy, and the long-term implications of right heart dysfunction observed in the postnatal period.

Sex Differences in Outcomes of Adults With Isolated Coarctation of the Aorta.

Background: Data are limited about the effect (or lack thereof) of sex on clinical outcomes in adults with coarctation of the aorta (COA). The purpose of this study was to compare atherosclerotic cardiovascular disease (ASCVD) risk profile, blood pressure (BP) data, echocardiographic indices, and mortality between men and women with COA. Methods: Retrospective study of adults with COA, and no associated left-sided obstructive lesions, who received care at Mayo Clinic (2003-2022). ASCVD risk profile was assessed as the prevalence of hypertension, hyperlipidemia, type 2 diabetes, obesity, smoking history, and coronary artery disease. A 24-hour BP monitor was used to assess daytime and nighttime BP and calculate nocturnal dipping. Results: Of 621 patients with isolated COA, 375 (60%) were men, and 246 (40%) were women. Women had similar ASCVD risk profile and daytime BP as men. However, women had less nocturnal dipping (7 ± 5 mm Hg vs 16 ± 7 mm Hg, P < 0.001), higher pulmonary artery mean pressure (23 mm Hg [interquartile range: 16-31] vs 20 mm Hg [interquartile range: 15-28], P = 0.04), and higher pulmonary vascular resistance index (3.41 ± 1.14 WU · m2 vs 3.02 ± 0.76 WU · m2, P = 0.006). Female sex was associated with all-cause mortality (adjusted hazard ratio 1.26, 95% confidence interval 1.04-1.94) and cardiovascular mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.09-2.18). Conclusions: Women had a higher risk of both cardiovascular mortality and all-cause mortality compared to the risks in men. This difference may be related to the higher-than-expected ASCVD risk factors, abnormal nocturnal blood pressure, and pulmonary hypertension observed in women in this cohort. Further studies are required to identify optimal measures to address these risk factors.

Contexte: Il existe peu de données sur l'issue clinique en fonction du sexe chez les adultes présentant une coarctation de l'aorte (CoA). Le but de cette étude consistait donc à comparer le profil de risque de maladie cardiovasculaire athéroscléreuse (MCVAS), les données relatives à la pression artérielle (PA), les indices échocardiographiques et le taux de mortalité chez des hommes et des femmes présentant une CoA. Méthodologie: Il s'agissait d'une étude rétrospective réalisée chez des adultes présentant une CoA en l'absence de lésions obstructives gauches, soignés à la clinique Mayo entre 2003 et 2022. Le profil de risque de MCVAS a été évalué en fonction de la prévalence de l'hypertension, de l'hyperlipidémie, du diabète de type 2, de l'obésité, des antécédents tabagiques et de la coronaropathie. Une surveillance sur 24 heures a été utilisée pour évaluer la PA diurne et nocturne, en plus de calculer la chute nocturne de la PA. Résultats: Parmi les 621 patients présentant une CoA isolée, 375 (60 %) étaient des hommes et 246 (40 %) étaient des femmes. Les femmes présentaient une PA diurne et un profil de risque de MCVAS semblables aux hommes. Elles présentaient néanmoins une chute nocturne de la PA moins prononcée (7 ± 5 mmHg vs 16 ± 7 mmHg, p < 0,001), une pression artérielle pulmonaire moyenne plus haute (23 mmHg [max.-min. : 16-31] vs 20 mmHg [max.-min. : 15-28], p = 0,04) et un indice de résistance vasculaire pulmonaire plus élevé (3,41 ± 1,14 UW · m2 vs 3,02 ± 0,76 UW · m2, p = 0,006). Le sexe féminin a été associé à un plus fort taux de mortalité toutes causes confondues (rapport de risques ajusté : 1,26; intervalle de confiance à 95 % : 1,04-1,94) et de mortalité cardiovasculaire (rapport de risques ajusté : 1,38; intervalle de confiance à 95 % : 1,09-2,18). Conclusions: Les femmes sont exposées à un risque de mortalité cardiovasculaire et de mortalité toutes causes confondues plus élevé que les hommes. Cette différence pourrait être attribuable au rôle plus important que prévu joué par les facteurs de risque de MCVAS ainsi qu'à la pression artérielle nocturne anormale et à l'hypertension pulmonaire chez les femmes de cette cohorte. D'autres études sont nécessaires pour savoir quels seraient les paramètres optimaux qui permettraient d'évaluer ces facteurs de risque.

Prognostic Value of Aortic Valve Calcification in Nonsevere Aortic Stenosis with Preserved Ejection Fraction.

BACKGROUND: Aortic valve calcification(AVC) is prognostic in patients with aortic stenosis(AS). We assessed the AVC prognostic value in nonsevere AS patients. METHODS AND RESULTS: We conducted a retrospective study of 395 patients with nonsevere AS, LV ejection fraction ≥50%. The Agatston method was used for computed tomography AVC assessment. The log-rank test determined the best AVC cutoffs for survival under medical surveillance: 1185 AU in men and 850 in women, lower than the established-cutoffs for severe AS(2064AU in men and 1274 in women). Patients were divided into three AVC groups based on these cutoffs: low(<1185 AU men and <850 women), sub-severe(1185-2064AU men and 850-1274 women) and severe(>2064AU men and >1274 women). Of 395 patients(mean age 73 ± 12 years, 60.5% men, aortic valve area 1.23 ± 0.30cm2, mean pressure gradient 28 ± 8 mmHg), 218 underwent aortic valve intervention(AVI) and 158 deaths occurred during follow-up, 82 before AVI. Median survival time under medical surveillance was 2.1[0.7-4.9]years. Compared to the low AVC group, both sub-severe and severe AVC groups had higher risk for all-cause death under medical surveillance after comprehensive adjustment including echocardiographic AS severity and coronary artery calcium score(all p ≤ 0.006); while mortality risk was similar between sub-severe and severe AVC groups(all p ≥ 0.2). This mortality risk pattern persisted in the overall survival analysis after adjustment for AVI. AVI was protective of all-cause death in the sub-severe and severe AVC(all p ≤ 0.01), but not in the low AVC groups. CONCLUSIONS: Sub-severe AVC is a robust risk-stratification parameter in patients with nonsevere AS and may inform AVI timing.

Invasive Cardiac Hemodynamics in Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy. METHODS AND RESULTS: Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right-sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right-sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise-induced elevation in left ventricular filling pressures. CONCLUSIONS: In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right-sided heart failure.

Coarctation of Aorta With Tricuspid Aortic Valve Is Not Associated With Ascending Aortic Aneurysm.

BACKGROUND: Aortic aneurysm is common in patients with coarctation of aorta (COA), but it is unclear whether the risk of aortic aneurysms is due to COA or related to the presence of other risk factors such as bicuspid aortic valve (BAV) and hypertension. OBJECTIVES: The purpose of this study was to assess the relationship among COA, BAV, and thoracic aortic aneurysms. METHODS: A total of 867 patients with COA (COA group) were matched 1:1:1 to 867 patients with isolated BAV (BAV group) and 867 patients without structural heart disease (SHD) (no-SHD group). The COA group was further subdivided into a COA+BAV subgroup (n = 304 [35%]), and COA with tricuspid aortic valve (TAV) (COA+TAV subgroup [n = 563 (65%)]). Aortic dimensions were assessed at baseline and at 3, 5, and 7 years. RESULTS: Compared with the no-SHD group, the COA+BAV subgroup had larger aortic root diameter (37 mm [Q1-Q3: 30-43 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001) and mid ascending aorta dimeter (34 mm [Q1-Q3: 29-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P = 0.008). Similarly, the BAV group had larger aortic root diameter (37 mm [Q1-Q3: 30-42 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001), and mid ascending aorta dimeter (35 mm [Q1-Q3: 30-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P < 0.001). Compared with the COA+TAV subgroup, the COA+BAV subgroup and BAV group were associated with larger aortic root and mid ascending aorta diameter at baseline and follow-up. The risk of acute aortic complications was low in all groups. CONCLUSIONS: These findings suggest that BAV (and not COA) was associated with ascending thoracic aorta dimensions, and that patients with COA+TAV were not at a greater risk of developing ascending aortic aneurysms as compared with patients without SHD.