Jain, C. Charles

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 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 Exercise cardiac catheterization is the gold standard for diagnosing diastolic dysfunction and impaired pulmonary reserve in patients with Fontan circulation. The diagnostic value of noninvasive parameters is unclear. Methods Patients who underwent simultaneous exercise hemodynamic evaluation and peripheral venous pressure (PVP) measurement were included. Echocardiographic surrogates for ventricular filling pressure were compared with invasive measures. Diastolic dysfunction was defined invasively as either resting pulmonary artery wedge pressure ≥12 mm Hg or exercise pulmonary artery wedge pressure >20 mm Hg. Results Twenty‐nine patients were included. Age at catheterization was 34±9 years. Atrioventricular valve systole‐to‐diastole duration ratio (S/D) and resting PVP were significant predictors of resting pulmonary artery wedge pressure (S/D: β=0.71 per 0.1 S/D [95% CI, 0.16–1.25]; P =0.01; PVP: β=0.68 per mm Hg [95% CI, 0.41–0.96]; P <0.001). By contrast, resting PVP was a predictor of diastolic dysfunction, whereas S/D was not. Based on these data, we proposed a 2‐tier assessment algorithm with the first tier considering resting PVP ≤15 mm Hg and S/D ≤1.1 and the second tier considering exercise PVP ≤25 mm Hg in those with 1 elevated resting parameter. This algorithm showed a positive predictive value of 88% (95% CI, 47%–100%), a negative predictive value of 90% (95% CI, 70%–99%), a sensitivity of 78% (95% CI, 40%–97%), and a specificity of 95% (95% CI, 75%–100%). Exercise PVP indexed to peak oxygen consumption also predicted invasively measured exercise pulmonary vascular resistance index (β=0.36 WU·m 2 per mm Hg/100 mL per min [95% CI, 0.08–0.64]; P =0.01). Conclusions This study presents a simple, noninvasive approach for evaluating diastolic function and pulmonary vascular reserve in patients with a Fontan circulation.

ABSTRACT Background The assessment of aortic stenosis (AS) severity remains a challenge in some patients, and hemodynamic exercise testing has been proposed as a diagnostic tool in this population. However, the current understanding of exercise hemodynamics in AS is limited. Methods Retrospective review of 34 adults (aged ≥ 18 years) with ≥ moderate AS and preserved left ventricular ejection fraction (LVEF) undergoing exercise invasive hemodynamics (supine cycle protocol) with simultaneous measurement of aortic and left ventricular pressures. Results Age was 77.1 (IQR 68.6; 84.1) years, and 50% were female. LVEF was 62.1 ± 6.6%. All patients were symptomatic. Resting aortic valve area (AVA) was 1.0 ± 0.2 cm 2 and aortic valve (AV) systolic mean gradient 22.0 ± 7.3 mmHg. At peak exercise (40 [IQR 30; 60] W), AV systolic mean gradient (Δ3 [0.6; 7] mmHg, p < 0.001) and AVA (Δ0.2 [0; 0.6] cm 2 , p = 0.002) significantly increased, while stroke volume (SV) did not (Δ6.8 ± 19.4 ml; p = 0.07). Exercise‐induced changes in AV systolic mean gradient were directly related to changes in cardiac output ( r = 0.53, p = 0.003), being inversely related to exercise systemic vascular resistance ( r = −0.60, p = 0.002). Elevated pulmonary artery wedge pressure was present in 41.2% at rest (≥ 15 mmHg) and 69.7% during exercise (≥ 25 mmHg). Conclusions Symptomatic patients with ≥ moderate AS and preserved LVEF experience small increases in AV mean gradient with exercise, and unlike the normal physiological response to exercise, there was no significant increase in SV. In most patients, AVA rose during exercise. Exercise‐induced elevation in filling pressures was highly prevalent.

BACKGROUND: Exercise-induced hypertension (EIH) is common in adults with coarctation of the aorta (COA), but there are limited data about hemodynamics and outcomes in such patients. The purpose of this study was to assess changes in arterial load during exercise in patients with COA with versus without EIH, and the relationship to clinical outcomes. METHODS: We compared Doppler-derived arterial load indices (effective arterial elastance index, total arterial compliance index, systemic vascular resistance index), and clinical indices of disease severity (pulmonary congestion, aerobic capacity, and cardiovascular biomarkers) between adults with repaired COA and healthy controls. EIH was defined as systolic blood pressure (BP) at peak exercise >210 mm Hg in men or >190 mm Hg in women. RESULTS: In this prospective cohort study, we assessed patients with COA (n=41, age 43±14 years, 26 [63%] men) and healthy controls (n=41). Although both groups had similar resting systolic BP, the COA group had higher Doppler-derived arterial load indices at rest, as well as a greater rise in systolic BP and Doppler-derived arterial load indices at each stage of exercise, leading to a higher prevalence of EIH in the COA group (37% versus 10%; P =0.004). Compared with patients with COA without EIH (n=26, 63%), those with EIH had higher arterial load at rest and during exercise, as well as worse cardiac dysfunction, pulmonary congestion, and biomarkers of cardiovascular remodeling, despite no significant differences in resting systolic BP. CONCLUSIONS: BP assessment during exercise can improve risk stratification and identify patients who may benefit from intensification of medical therapy.

Abstract Aims Pulmonary regurgitation (PR) after reparative intervention for congenital heart disease has been studied extensively. However, the burden, distribution of causes, and outcome of PR in adults is unknown. The study aimed to evaluate the prevalence, types, and outcomes of moderate/severe PR in adults in the community setting. Methods and results A total of 398 adult residents of Olmsted County who had clinically indicated echocardiography 2004–2023 at Mayo Clinic, Rochester, and had moderate or severe PR were identified retrospectively. The median age was 77 years, 48% were females, and 61 (51%) had severe PR. The age- and sex-adjusted US prevalence was 0.11% (vs. 0.67% for ≥moderate tricuspid regurgitation). Moderate/severe PR was due to pulmonary hypertension in 77%, congenital/iatrogenic in 11%, primary pulmonary valve disease in 2% (88% due to carcinoid), and idiopathic isolated in 10%. In contrast, severe PR was due to congenital/iatrogenic disease in 52%, pulmonary hypertension in 39%, primary PR in 5%, and isolated idiopathic in 3%. The all-cause mortality rate per 100 person-year was 73 in primary (mostly carcinoid) PR, 16 in pulmonary hypertension–related PR (not different vs. propensity-matched patients without PR), and 6 in isolated idiopathic PR (not different vs. matched patients without PR). Conclusion Moderate or severe PR had a lower prevalence vs. TR. The most frequent cause was pulmonary hypertension for ≥moderate PR and congenital/iatrogenic for severe PR. Mortality in patients with acquired ≥moderate PR appeared to be related to the underlying cause, with no excess mortality compared with matched patients without PR. Whether specifically severe PR confers excess mortality requires future investigation.

Abstract Aims The effects of obesity on Fontan haemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive haemodynamics and exercise capacity. Methods and results Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity [body mass index (BMI) &gt; 30 kg/m2] and overweight/normal BMI (BMI ≤ 30 kg/m2). There were 18 individuals with obesity (BMI 36.4 ± 3 kg/m2) and 59 with overweight/normal BMI (BMI 24.1 ± 3.6 kg/m2). Peak oxygen consumption (VO2) on non-invasive cardiopulmonary exercise testing was lower in patients with obesity (15.6 ± 3.5 vs. 19.6 ± 5.8 mL/kg/min, P = 0.04). At rest, systemic flow (Qs) [7.0 (4.8; 8.3) vs. 4.8 (3.9; 5.8) L/min, P = 0.001], pulmonary artery (PA) pressure (16.3 ± 3.5 vs. 13.1 ± 3.5 mmHg, P = 0.002), and PA wedge pressure (PAWP) (11.7 ± 4.4 vs. 8.9 ± 3.1 mmHg, P = 0.01) were higher, while arterial O2 saturation was lower [89.5% (86.5; 92.3) vs. 93% (90; 95)] in obesity compared with overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7 ± 6.5 vs. 24.7 ± 6.8 mmHg, P = 0.01) and PAWP (23.0 ± 6.5 vs. 19.8 ± 7.3 mmHg, P = 0.047), but lower arterial O2 saturation [82.4 ± 7.0% vs. 89% (85; 92), P = 0.003]. Conclusion Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared with those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve haemodynamics and outcomes requires further study.