Jain, Chirag

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: 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.