Citations

Abstract Background and Aims The aim of the study was to assess the effect of guideline-directed medical therapy (GDMT) on cardiac function, neurohormonal activation, and mortality in adults with congenitally corrected transposition of the great arteries (cc-TGA) presenting with systemic right ventricular (RV) systolic dysfunction. The study hypothesis was that GDMT use (assessed using the GDMT score) was associated with improved cardiac function (higher RV free wall strain [RVFWS]), less neurohormonal activation (lower N-terminal pro-B-type natriuretic peptide [NT-proBNP] levels), and lower mortality. Methods GDMT score, RVFWS, and NT-proBNP levels were assessed at baseline and 1-year follow-up. GDMT uptitration was assessed using ΔGDMT (GDMT at 1-year minus GDMT at baseline). Improvements in RV systolic function and neurohormonal activation were defined as a relative increase in RVFWS of >20% and a relative decrease in NT-proBNP levels of >20%, respectively. Results Of 213 patients (age 43 ± 15 years; 54% male), baseline GDMT score was 1.97 ± 1.27, and ΔGDMT score was 0.74 ± 0.39. Baseline RVFWS was −18 ± 5%; 25% had improved RV systolic function. Baseline NT-proBNP was 369 (142, 1004) pg/mL; 56% had improved neurohormonal activation. Higher baseline GDMT score and ΔGDMT score were associated with improvement in RV systolic function and neurohormonal activation. Overall, 34 (16%) patients died, and higher baseline GDMT score and ΔGDMT score were associated with a lower risk of mortality and of the composite adverse event endpoint (heart failure hospitalization, death, and heart transplantation). Clinical benefits of GDMT use were observed only in patients with moderate/severe RV systolic dysfunction, and not in patients with mild RV systolic dysfunction. Conclusions GDMT use was associated with improved outcomes in patients with moderate/severe RV systolic dysfunction.

Abstract Carcinoid heart disease (CHD) is associated with advanced neuroendocrine tumor liver metastases (NETLM) and may preclude surgical cytoreduction. We assessed perioperative and long‐term outcomes of hepatectomy in patients with CHD. We retrospectively analyzed 311 patients undergoing cytoreductive hepatectomy for intestinal NETLM: non‐functional ( n = 163), carcinoid syndrome (CS) without CHD ( n = 110), and CHD ( n = 38), including patients undergoing pre‐hepatectomy valve replacement. CHD patients more frequently had >10 liver metastases (78%) and larger lesions (median 9.5 cm) and required major hepatectomy more often (58%). Major morbidity was higher in CHD (up to 47%), yet 90‐day mortality remained low (≤4%). Median overall survival after hepatectomy was comparable across groups (12.5 vs. 9.1 vs. 11.4 years; p = .19), including matched analyses. With optimal cardiac management, cytoreductive hepatectomy in CHD is feasible and provides long‐term survival comparable to patients without CHD.

Background Cardiovascular biomarkers such as NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) are used for heart failure risk stratification in patients with acquired heart disease, but there are limited data about its role in patients with congenitally corrected transposition of the great arteries. The current study aims to assess the role of serial NT‐proBNP measurements for risk stratification in adults with congenitally corrected transposition of the great arteries. Methods We studied adults with congenitally corrected transposition of the great arteries with ≥2 NT‐proBNP measurements (2003–2024). Temporal change in NT‐proBNP was calculated as relative change from baseline levels. Results Of 152 patients (age 47±13 years, 45% men), baseline NT‐proBNP was 539 (interquartile range, 193–1549) pg/mL, and relative change from baseline levels of NT‐proBNP was 34% (interquartile range, −11 to 67). Of 152 patients, 45 (30%) had cardiovascular events (heart failure hospitalization [n=29], ventricular assist device [n=5], heart transplantation [n=11], and death [n=10]), yielding a 10‐year incidence of 26%. Higher baseline NT‐proBNP and relative change from baseline levels were associated with cardiovascular events. Serial NT‐proBNP measurements had incremental prognostic value compared with baseline measurement. The correlates of higher NT‐proBNP levels were atrial fibrillation, hypertension, right ventricular dilation and dysfunction, and atrioventricular valve regurgitation. Renin–angiotensin–aldosterone system antagonist was associated with lower NT‐proBNP levels and lower risk of cardiovascular events. Conclusions NT‐proBNP testing is inexpensive, widely available, and noninvasive, making it well suited for longitudinal surveillance in adults with congenital heart disease. Most of the correlates for elevated NT‐proBNP levels were modifiable, providing target for therapeutic interventions.

Background Mortality in adults with congenital heart disease (CHD) is strongly driven by disease complexity. Social determinants of health (SDOH) influence adult CHD (ACHD) health outcomes but their impact on mortality is unclear. This study examined the influence of clinical factors and SDOH on all‐cause mortality in patients with ACHD. Methods Single‐center retrospective cohort study of patients with ACHD in the Mayo ACHD Registry who had a verifiable residential address between January 1, 2004 and December 31, 2023. Clinical and SDOH indicators were extracted, including insurance type, language, rural–urban commuting area code, and a housing‐based socioeconomic index, an individual‐level measure of socioeconomic status derived from 4 objective housing characteristics and categorized into quartiles (Q1–Q4). Cox proportional‐hazards models were fitted to evaluate associations with mortality, incorporating CHD severity, arrhythmias, SDOH indicators, and other comorbidities. County of residence was included as a random effect, and model discrimination was assessed using the concordance statistic. Results Among 6134 patients with ACHD, the mean age was 38±16 years; 51% were male; 78.7% were White and 44.9% had rural residence. Independent predictors of mortality included cyanotic CHD (adjusted hazard ratio [aHR], 5.70 [95% CI, 2.90–11.23]), Fontan palliation (aHR, 4.98 [95% CI, 2.56–9.70]), ventricular tachycardia (aHR, 1.71 [95% CI, 1.16–2.52]), older age at first visit (aHR, 1.05 per year [95% CI, 1.04–1.05]), male sex (aHR, 1.19 [95% CI, 1.03–1.39]), public insurance (aHR, 1.60 [95% CI, 1.35–1.90]), rural residence (aHR, 1.25 [95%, CI 1.06–1.47]), and non‐English language (aHR 1.75 [95% CI 1.38–2.23]). The housing‐based socioeconomic index quartile was not associated with mortality. The final model achieved a concordance statistic of 0.77. Conclusions Mortality in patients with ACHD is strongly influenced by both clinical factors and SDOH, independent of socioeconomic status. Addressing barriers to care such as language, insurance, and geography is essential for improving ACHD survival particularly in those at increased mortality risk.

Abstract Aims Echo-derived left atrial (LA) stiffness index improves prognostication in patients with heart failure preserved ejection fraction but has not been studied in adults with repaired coarctation of aorta (COA). We hypothesized that, among adults with COA, those with high LA stiffness index would have worse disease severity indices [peak VO2, NT-proBNP, and right ventricular to pulmonary artery (RV-PA) coupling], heart failure hospitalization, and all-cause mortality. Methods and results LA stiffness index was estimated using the baseline echocardiogram as the quotient of septal E/e′ and LA reservoir strain (E/e′/LARS). Using the median septal LA stiffness index as the cut-off, patients were divided into high LA stiffness index (LA stiffness index >0.28) vs. low LA stiffness index groups (LA suggests index ≤0.28). The study comprised of 729 patients [age 36 ± 16 years; males 437 (60%)]. LA stiffness index correlated with RV-PA coupling (r = −0.56, P < 0.001), NT-proBNP (r = 0.62, P < 0.001), and predicted peak VO2 (r = −0.51, P < 0.001). High LA stiffness index was associated with heart failure hospitalization (adjusted HR 3.17, 95% confidence interval (CI) 1.84–7.36, P = 0.007) and all-cause mortality (adjusted HR 2.81, 95% CI 1.28–12.32, P = 0.005). LA stiffness index had superior prognostic performance for predicting 5-year risk of heart failure hospitalization (AUC 0.803, 95% CI 0.756–0.849, P < 0.001) and all-cause mortality (AUC 0.786, 95% CI 0.742–08.30, P < 0.001) compared with conventional echocardiographic indices of left heart diastolic function. Conclusion LA stiffness index improves prognostication in adults with COA and can potentially be used to guide timing of intervention or monitor response to therapy.

Abstract Background and Aims Decrease in pulmonary vascular resistance (PVR) during exercise confers favourable prognosis in biventricular physiology, but its role in Fontan circulation remains unknown. This study aimed to evaluate the prognostic value of PVR index (PVRI) response to exercise in adults post-Fontan palliation. Methods Retrospective cohort of 88 adults (age ≥18 years) post-Fontan undergoing exercise (supine cycling) cardiac catheterization. Patients were categorized into absence (n = 23) or presence (n = 65) of exercise-induced reduction in PVRI. The clinical endpoint was a composite of death or transplantation. Results Age at catheterization was 32.2 ± 8.8 years, and 45.5% were female. Resting and exercise PVRI were 1.9 ± 0.9 and 1.2 (interquartile range [IQR] 0.8–2.1) WU·m2, respectively. Clinical, biochemical and echocardiographic parameters were not associated with PVRI response to exercise. During a follow-up of 2.2 ± 1.4 (IQR 1.2–2.6) years, resting PVRI was not associated with the clinical endpoint (hazard ratio [HR] 0.95 per WU·m2, 95% confidence interval [CI] 0.52–1.74; P = 0.86), whereas exercise PVRI was (HR 2.15 per WU·m2, 95% CI 1.24–3.73; P = .007). Exercise PVRI remained predictive of outcomes after adjusting for exercise pulmonary artery wedge pressure (HR 2.08 per WU·m2, 95% CI 1.19–3.62; P = .01) or clinical risk factors individually. Two-year event-free survival was lower in the no PVRI reduction than in the reduction group (67% vs 95%; P < .001). Conclusions In adults post-Fontan, PVRI response to exercise is a robust predictor of clinical outcomes and offers additive prognostic information beyond resting invasive haemodynamic data and clinical risk factors, underscoring the importance of invasive exercise testing in this population.

Background: Heart failure (HF) is the leading cause of mortality in adults with congenital heart disease (CHD) after transcatheter pulmonary valve replacement (TPVR), likely due to preexisting myocardial dysfunction and suboptimal reverse remodeling. Left ventricular (LV) diastolic dysfunction, unmasked by an acute increase in preload post-TPVR, may elevate left-sided filling pressures and precipitate pulmonary edema. However, the prognostic implications of elevated left-sided filling pressures prior to TPVR are currently unknown. Objective: To evaluate the prognostic value of pre-TPVR pulmonary artery wedge pressure (PAWP) and the heart failure with preserved ejection fraction – Age, Body mass index (BMI), Atrial fibrillation (HFpEF-ABA) score in patients undergoing TPVR. Methods: Adults with congenital heart disease (CHD) undergoing TPVR were stratified by pre-implant PAWP (<15 vs ≥15 mmHg) and HFpEF-ABA score (low <25%, intermediate 25–75%, high >75%). The composite endpoint was all-cause mortality, heart transplantation, heart failure (HF) hospitalization, or sustained ventricular arrhythmia. Kaplan-Meier and Cox regression analyses assessed associations with clinical outcomes. Results: Out of 150 patients, 37 (24.7%) had PAWP ≥15 mmHg. Elevated PAWP was associated with older age (36 [31;53] vs. 26 [19; 37] years, p<0.01), BMI (27.9 [24.5; 35.1] vs. 24.2 [20.6; 29.7] kg/m 2 , p<0.01), and higher HFpEF-ABA score (42.8 [9.5;63.6] vs. 6.4 [2.5;18.1]%, p<0.001) compared to normal PAWP. Over a median follow-up of 38 [13; 83] months, 26 events (17.3%) occurred. Kaplan-Meier analysis demonstrated a significant difference in event-free survival based on pre-TPVR PAWP categories (log-rank p=0.002) and HFpEF-ABA score categories (log-rank p<0.001). Elevated PAWP was associated with adverse outcomes (hazard ratio [HR] 4.27, 95% CI 1.61–11.31, p=0.003) (Figure 1), but this was no longer significant after age adjustment. HFpEF-ABA ≥25% was associated with adverse outcomes (HR 10.6, 95% CI 3.8–30.0, p<0.001) (Figure 2), independent of N-terminal prohormone of brain natriuretic peptide levels and left ventricular ejection fraction. Conclusion: Albeit confounded by demographics, pre-TPVR PAWP correlated with adverse long-term outcomes, and patients with this hemodynamic profile may require closer post-procedural surveillance. HFpEF-ABA was independently associated with incident events, representing an inexpensive, novel prognostic tool in patients undergoing TPVR.

Background: Patients with systemic right ventricle (sRV), including congenitally corrected transposition of great arteries (cc-TGA) and dextro-transposition of great arteries (d-TGA) post-atrial switch procedure are at risk of sudden cardiac death due to ventricular arrhythmias (VA). While programmed ventricular stimulation (PVS) can help with risk stratification in certain patients with congenital heart disease, its role in sRV is unknown. Objective: To study the diagnostic value of electrophysiology study (EPS) in predicting VAs in patients with sRV. Methods: EPS was performed in 53 patients with sRV at Mayo Clinic from 1994 to 2021. Patients with a history of sustained VA or cardiac arrest were excluded (n=19). The incidence of sustained VA (sudden cardiac death, sustained ventricular tachycardia [VT] or appropriate implantable cardioverter-defibrillator [ICD] therapy) was evaluated in the remaining 34 patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EPS in predicting VAs is reported. Results: The mean age at EPS was 36.2±11.6 years, 21 (61.8%) were male, 21 (61.8%) had d-TGA and mean sRV ejection fraction was 31.3±10.8%. Indication for EPS was supraventricular tachycardias (n=15, 44.1%), syncope/palpitations (n=9, 26.5%) and non-sustained VT (n=6, 17.6%). 13/34 (38.2%) patients had inducible sustained VA, (5 [38.5%] with monomorphic VT and 8 [61.5%] with polymorphic VT/VF). Treatments included ICD implantation in all 13 patients and ablation in one patient. During a mean follow-up of 8±5.4 years, one patient with a positive PVS (inducible polymorphic VT) experienced sustained VT secondary to atrial flutter with 1:1 conduction. The sensitivity of PVS was 100%, specificity was 63.6%, PPV 7.7%, and NPV 100%. Conclusion: In this retrospective cohort of patients with sRV, polymorphic VT was the most commonly observed VA during PVS. The predictive value of a positive PVS was low in this cohort, and larger studies are needed to better define the role of EPS in risk stratification. Patients with negative EPS did not have future VAs recognizing that the overall event rate is low. Further multicenter research with a larger sample is required to develop predictive models to identify those at risk of VAs.

Backround: Advances in surgical and medical care of children born with congenital heart disease (CHD) has improved survival into adulthood. However, cardiac and non-cardiac morbidity and mortality remain common in adults with CHD (ACHD). We present the causes and predictors of mortality in a large cohort of ACHD patients from the USA. Methods/Approach: We conducted a retrospective review of ACHD patients followed at Mayo Clinic between 1992 - 2024. Mortality was ascertained using the Accruint national data base. Clinical characteristics and primary cause of death were identified from the electronic record. Kaplan-Meier (KM) survival analysis was performed to compare overall survival stratified by CHD severity. Cox proportional hazards regression was used to identify independent predictors of mortality. Results/Data: Amongst 9160 ACHD patients (mean age 38±16y at first visit, 51% males, 23% simple, 59% moderate and 18% severe CHD), mortality occurred in 1430(16%) patients during a mean follow-up of 11±7y. The mean age at death was 68±17 y, 58±17y, and 45±15y in mild, moderate and severe ACHD. KM analysis of survival and cause of death stratified by CHD severity are presented in Figures 2 and 3 respectively. Cause of death could not be ascertained in 33%%. Amongst those with a known cause of death, the proportion of non-cardiac death increased with decreasing severity of CHD. HF death and sudden cardiac death occurred in 11% and 19%. Infection, malignancy and chronic respiratory failure were important non-cardiac causes of death. Significant risk factors for mortality included CHD severity, ventricular arrhythmia, heart failure, declining functional capacity, diabetes and chronic kidney disease as presented in the Fig 1. Conclusion(s): Mortality in ACHD patients is associated with CHD severity, heart failure, ventricular arrhythmia and cardiovascular comorbidities. Early recognition and management of these risk factors may improve long-term survival. As patients with ACHD age, management of cardiovascular and noncardiac risk factors will require development of systems of care specific to this vulnerable population.

Background: Fontan circulation is characterized by the absence of a subpulmonary ventricle with resultant systemic venous hypertension. Despite exercise intolerance being nearly universal in this population, the determinants of exercise capacity in this population are still poorly understood. Research Question: We investigated the prevalence of peripheral impairment and assessed the contribution of peripheral O 2 extraction versus central hemodynamics to peak O 2 consumption (pVO 2 ) post-Fontan palliation. Methods: This single-center retrospective cross-sectional study compared 52 consecutive adults post-Fontan procedure who underwent exercise catheterization to patients with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnea (NCD) at 1:1 ratio. Several previously reported measures for peripheral O 2 extraction were evaluated in the absence of a golden standard. Correlates of pVO 2 were identified by multivariate linear regression analyses using the backward selection method. Results: Patients with Fontan circulation were younger [age 32 (24;36) years] and tended to have a lower body mass index [26 (23; 29) kg/m 2 ] compared to patients with HFpEF [70 (57; 75) years, p<0.001 and 33 (27; 39) kg/m 2 , p<0.001] and NCD [48 (38; 61) years, p<0.001 and 27 (24; 35) kg/m 2 , p=0.08]. Peak heart rate [108 (85;126) vs 108 (95;125) bpm] and indexed stroke volume [46 (39;54) vs 45 (40;53) ml/m 2 ] were similar in the Fontan and HFpEF groups but lower compared to NCD [126 (108;141) bpm, p<0.001 and 51 (45;59) ml/m 2 , p<0.001]. Peak mean pulmonary artery pressures were highest in HFpEF [45 (41;50) mmHg, p<0.001], followed by Fontan and NCD [26 (22;31) vs 23 (19;25) mmHg, p=0.03]. Median peak O 2 extraction post-Fontan was comparable to HFpEF [12 (10;14) vs 11 (10;13) ml/dl, p=0.17] but higher than in NCD [10 (9;12) ml/dl, p<0.001]. It was <14 ml/dl in 73% compared to 94% and 98% of patients with HFpEF and NCD [p<0.001]. O 2 extraction ratio was <70% in 62% compared to 60% in HFpEF and 96% in NCD [p<0.001]. Correlates of pVO 2 post-Fontan were peak O 2 extraction [β 0.5±0.1 per ml/dl; p<0.001], mean pulmonary artery pressures [β -0.2±0.05 per mmHg; p=0.002], heart rate [β 0.03±0.01 per bpm; p=0.01], and systolic arterial blood pressure [β 0.03±0.01 per mmHg; p=0.02]. Conclusion: Impaired O 2 extraction is prevalent amongst adults post-Fontan. Whether exercise can modulate this important determinant of exercise capacity post-Fontan merits further investigation.