Reddy, Yogesh N.V.

Aims There are similarities in the pathogenesis of cardiac remodelling and dysfunction in heart failure with preserved ejection fraction (HFpEF) and coarctation of aorta (COA). We hypothesized that clinical HFpEF would be highly prevalent in adults with COA, and that the presence of HFpEF would increase the risk of mortality in this population. The aim of this study was to define the clinical features, haemodynamics, and prognostic implications of HFpEF in COA. Methods and results Consecutive adults with repaired COA that underwent right heart catheterization were identified retrospectively. HFpEF was defined as heart failure symptoms (exertional dyspnoea or fatigue), preserved left ventricular ejection fraction ≥50%, and pulmonary artery wedge pressure at rest >15 mmHg. Of 99 COA patients, 32 (32%) had HFpEF. The correlates of HFpEF were obesity (adjusted odds ratio [OR] 4.15, 95% confidence interval [CI] 1.31–13.2), atrial fibrillation (adjusted OR 3.13, 95% CI 1.00–10.7), total arterial compliance index (adjusted OR 0.12, 95% CI 0.06–0.41 per 1 ml/mmHg*m 2 ), and pulmonary artery compliance index (adjusted OR 0.36, 95% CI 0.15–0.56 per 1 ml/mmHg*m 2 ). Of 99 patients, 24 (24%) died and 5 (5%) underwent heart transplant. The 10‐year cumulative incidence of death/transplant was higher in COA patients with HFpEF compared with patients without HFpEF (39% vs. 12%, p = 0.001). The presence of HFpEF was associated with increased risk of death/transplant (adjusted hazard ratio 1.68, 95% CI 1.16–3.11). Conclusions Heart failure with preserved ejection fraction is common in adults with COA and is associated with greater risk of death/transplant, emphasizing a pressing need for interventions to prevent and treat HFpEF in COA.

Abstract 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.

Abstract Aims The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging based on resting assessments. Exercise echocardiography is often used to unmask abnormalities that develop during exercise, but the diagnostic criteria have not been standardized. This study aimed to elucidate how cardiologists utilize exercise echocardiography to diagnose HFpEF in real-world practice. Methods and results An international web-based survey involving 87 cardiologists was performed. We also performed a retrospective cross-sectional study to investigate the impact of different exercise echocardiographic diagnostic criteria in 652 dyspnoeic patients who underwent exercise echocardiography. The HFA-PEFF algorithm was the most commonly used exercise echocardiography criterion for HFpEF diagnoses (48%), followed by the ASE/EACVI criteria (24%) and other combinations of multiple parameters (22%). Among 652 patients, the proportion of HFpEF diagnosis varied substantially according to the criteria used ranging from 20.1% (ASE/EACVI criteria) to 44.3% (HFA-PEFF algorithm). Many cases (49.4–70.5%) remained indeterminate after exercise echocardiography, but only 41% of surveyed cardiologists would utilize exercise right heart catheterization to resolve an indeterminate result. Despite these diagnostic uncertainties, 54% of surveyed cardiologists would utilize exercise echocardiography results to initiate sodium–glucose co-transporter 2 inhibitors. Conclusion In real-world practice, exercise echocardiographic criteria utilized across cardiologists vary, which meaningfully impacts the frequency of HFpEF diagnoses, with indeterminate results being common. Despite these diagnostic uncertainties, many cardiologists initiate pharmacotherapy based on exercise echocardiography. The lack of consensus on universal diagnostic criteria for exercise echocardiography and approaches to indeterminate results may limit the delivery of evidence-based treatment for HFpEF.

Abstract Aims This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure–volume relationships, and reduced LV longitudinal contractile function. Conclusions Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

Introduction: Reduced peak oxygen consumption (VO 2 ) is common and associated with adverse outcomes in patients with heart failure (HF) and preserved ejection fraction (HFpEF). According to the Fick principle, VO 2 is equal to the product of cardiac output (CO) and arterial-venous O 2 difference (AVO 2 diff). Patients with HFpEF display abnormalities each component, but no study has yet evaluated their prognostic impacts. Methods: Patients with HFpEF (n=501) and controls without HF (n=207) underwent invasive hemodynamic exercise testing with expired gas analysis and clinical follow up for the composite event of HF hospitalization or death. Results: Compared to controls, patients with HFpEF displayed slightly lower CO at rest with higher pulmonary capillary wedge pressure (PCWP). On exercise, subjects with HFpEF displayed blunted increases in CO and greater increase in PCWP (Figure A). As compared with controls, the slope of the increase in CO relative to VO 2 was lower in HFpEF (6.4 ± 3.3 vs 5.4 ± 3.2 L/L; P =0.0004), while augmentation in AVO 2 diff relative to VO 2 was greater in HFpEF (7.7 ± 5.4 vs 10.0 ± 5.6 min/dL; P <0.0001). Over a median 2.8 (1.1-4.6) years of follow up, 101 patients experienced the composite event. Patients with CO reserve below the median and increases in AVO 2 diff below median displayed higher risk of the composite endpoint (Figure B-C). After adjustments for age, sex, BMI, atrial fibrillation, LV mass, and EF, CO reserve remained strongly associated with the primary outcome (HR [95%CI] = 0.51 [0.38-0.68]; P <0.0001, per 1 SD increase) and the change of AVO 2 diff remained significant, but was less predictive (HR [95%CI] = 0.74 [0.60-0.92]; P =0.007, per 1 SD increase) in patients with HFpEF. Conclusions: Impaired ability to augment CO and peripheral O 2 delivery are associated with increasing risk of adverse events in HFpEF. Further study is required to identify therapeutic interventions targeting these hemodynamic perturbations to improve outcomes in HFpEF.

Introduction: Many patients with heart failure with preserved ejection fraction (HFpEF) display normal N-terminal-pro-B type natriuretic peptide (NTproBNP)levels. Mortality and hospitalization rates are lower in this group compared to patients with high NTproBNP, but it remains unclear whether these patients represent a fundamentally different phenotype or an earlier stage of disease. Methods: 213 subjects with HFpEF defined by invasive hemodynamics underwent serial echocardiographic examinations &gt;1 year apart. Clinical, cardiac structural, functional, and hemodynamic characteristics were examined. Results: Exam 2 was performed a median of 3.2 years (IQR 2.2-5.1) following Exam 1. From this cohort, 66 (33%) displayed normal NT-proBNP levels (≤125pg/ml, nBNP) and 147 (67%) displayed high NTproBNP (hBNP). Compared to hBNP, nBNP patients were younger (62±10 vs 71±9 years, p&lt;0.0001) and more obese (35±8 vs 32±7 kg/m 2 , p=0.005). At Exam 1, approximately 50% of nBNP displayed left ventricular (LV) systolic dysfunction defined as LV longitudinal strain (GLS)&lt;16% ( Figure A ) and LA dysfunction defined as left atrial (LA) reservoir strain&lt;26% ( Figure B ), but right ventricular (RV) systolic function as relatively preserved ( Figure C ). At Exam 2, LV, LA, and RV strain decreased in both groups (Panels A-C), with no difference between nBNP and hBNP in the velocity of change (p&gt;0.6 for all). More patients crossed the threshold definition for LV systolic and LA dysfunction in nBNP compared to hBNP ( Figure D and E ), but the prevalence of RV dysfunction increased more in hBNP ( Figure F ). Conclusions: In patients with HFpEF with normal NT-proBNP, biventricular systolic function and LA function deteriorate over time at similar pace. These data suggest that patients with HFpEF are not a fundamentally different disorder, but rather represent an earlier stage of disease that progresses from LV and LA dysfunction in early stages to RV dysfunction in advanced stages.