Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial.

Background: Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalisation for heart failure in patients with heart failure and reduced ejection fraction (HFrEF) following a recent worsening event. The aim of the VICTOR trial was to assess the effect of vericiguat in patients with HFrEF without recent heart failure worsening.

Methods: In this double-blind, placebo-controlled, phase 3 trial, conducted at 482 sites across 36 countries, patients aged 18 years or older with HFrEF (left ventricular ejection fraction of ≤40%) without heart failure hospitalisation within 6 months or outpatient intravenous diuretic use within 3 months before randomisation were randomly assigned (1:1) using an intervention randomisation system with interactive response technology to oral vericiguat (target 10 mg dose) or matching placebo.

Vericiguat for patients with heart failure and reduced ejection fraction across the risk spectrum: an individual participant data analysis of the VICTORIA and VICTOR trials.

Background: Following completion of the VICTORIA trial, vericiguat was approved for the treatment of worsening heart failure with reduced ejection fraction (HFrEF) and received a class IIb recommendation in European and North American guidelines. The subsequent VICTOR trial evaluated the use of vericiguat in patients with HFrEF and no recent worsening. We aimed to assess the effect of vericiguat on clinical endpoints through pooled analyses of patient-level data from the VICTORIA and VICTOR trials.

Effect of Vericiguat on Worsening Heart Failure in Compensated Outpatients with HFrEF: Insights from VICTOR.

Background: In the VICTOR trial, in a contemporary ambulatory cohort with heart failure and reduced ejection fraction (HFrEF) and no recent hospitalization, the primary outcome of hospitalization for heart failure (HHF) and cardiovascular death was not statistically significantly reduced with vericiguat. Vericiguat reduced risk of mortality but not HHF. In this ambulatory compensated cohort, time to first HHF may underestimate the overall worsening HF burden by failing to consider the high proportion of outpatient worsening HF events.

Vericiguat and mortality in heart failure and reduced ejection fraction: the VICTOR trial.

Background And Aims: In the VICTOR trial (NCT05093933), vericiguat was neutral for the primary composite endpoint of cardiovascular death or hospitalization for heart failure (HF). VICTOR was powered to independently assess cardiovascular death. This study reports detailed analysis on the effects of vericiguat on mortality.

Feasibility, Reproducibility, and Prognostic Value of Exercise Echocardiography for Cardiac Output Reserve Assessment in Fontan Physiology.

Background: The purpose of this study was to assess the feasibility and prognostic value of cardiac output (CO) reserve assessment using exercise echocardiography in Fontan patients. We hypothesized that adults with Fontan palliation had lower CO reserve compared with controls, and impaired CO reserve was associated with greater congestion (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) and cardiovascular events (death/transplant/heart failure hospitalization) in Fontan patients.

Methods: Thirty-seven Fontan patients and 61 controls underwent exercise echocardiography using a supine cycle ergometer.

Utility of HFpEF Diagnostic Scores to Stratify Cardiac Reserve Among Patients With Dyspnea.

Background: The heart failure with preserved ejection fraction (HFpEF) scores were initially developed to facilitate diagnosis of HFpEF in patients with dyspnea. Whether these diagnostic scores also relate to severity of cardiopulmonary reserve limitations across the broad range of patients with dyspnea, with or without confirmed HFpEF, remains unclear.

Objectives: The purpose of this study was to investigate the association between HFpEF scores and disease severity in patients with dyspnea.

Acute Effects of Myeloperoxidase Inhibition on Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Objective: Myeloperoxidase (MPO) is a heme peroxidase that scavenges nitric oxide and contributes to microvascular dysfunction. Patients with heart failure and preserved ejection fraction (HFpEF) have microvascular dysfunction that leads to increased pulmonary capillary wedge pressure (PCWP). We sought to investigate whether acute MPO inhibition can reduce exertional PCWP in patients with HFpEF.

Prognostic significance of unintentional weight loss in heart failure with preserved ejection fraction.

Aims: While intentional weight loss achieved through cardiometabolic medications has been associated with robust salutary effects in heart failure (HF) with preserved ejection fraction (HFpEF), the clinical significance of unintentional weight loss in this setting remains unclear.

Methods And Results: This retrospective cohort study included 434 overweight or obese patients with invasively proven HFpEF (67 ± 11 years, 236 female), without weight-reducing therapies or known malignancy, who underwent invasive hemodynamic cardiopulmonary testing and long-term clinical follow-up. The annualized weight change from index to final evaluation for the tertiles was: -21.

Determinants of submaximal exercise intolerance in patients with heart failure and preserved ejection fraction: Insights from the lactate threshold.

Aims: Oxygen consumption at peak exercise is widely used to assess functional impairment in heart failure with preserved ejection fraction (HFpEF), but few patients exercise to this intensity in daily living. Alternative metrics that quantify submaximal fitness may provide more patient-centred evaluations, but the pathophysiology of submaximal exercise intolerance in HFpEF is unexplored.

Methods And Results: Patients with HFpEF underwent invasive haemodynamic cardiopulmonary exercise testing with blood lactate measurement during exercise to volitional fatigue.

Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension.

A subset of patients with group 1 pulmonary hypertension (PH) have superimposed left heart abnormalities with unclear metabolic implications. To compare serum/transpulmonary metabolome between group 1 PH stratified by heart failure with preserved ejection fraction (HFpEF) probability. Patients with group 1 PH were stratified into low (<25%) and high (⩾75%) HFpEF-ABA (age, body mass index, and atrial fibrillation) probability, with healthy control subjects and subjects with clinical HFpEF used for comparison of venous and transpulmonary metabolomics.

Left Heart Abnormalities in Patients With Lung Disease, OSA, and Chronic Thromboemboli at Risk for or With Known Pulmonary Hypertension.

Background: Patients with lung disease, sleep apnea, and chronic thromboemboli can develop pulmonary hypertension, currently classified as group 3 or 4. Many of these patients also have risk factors for heart failure with preserved ejection fraction (HFpEF), but the optimal approach to identify the disease overlap remains unclear.

Methods: Pretest probability for HFpEF was determined using the HFpEF-ABA (age, body mass index, atrial fibrillation) algorithm among adjudicated group 3 or 4 patients at risk for pulmonary hypertension in the PVDOMICS study (Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics).

Disentangling the Impact of Adiposity From Insulin Resistance in Heart Failure With Preserved Ejection Fraction.

Background: Obesity, insulin resistance (IR), and diabetes are common in heart failure with preserved ejection fraction (HFpEF) and are associated with worsening heart failure, but their independent contributions remain unknown.

Objectives: In this study, we sought to determine the contribution of diabetes vs obesity to left heart abnormalities in HFpEF METHODS: Indices of adiposity (body mass index [BMI], bioimpedance fat mass, waist circumference) and IR (homeostasis-model assessment [HOMA]) were measured among PVDOMICS study participants with HFpEF. Rest and exercise pulmonary capillary wedge pressure (PCWP) responses were compared, stratified by obesity (BMI ≥30 kg/m), IR status (HOMA-IR ≥2.

Left ventricular-arterial coupling and mortality in the cardiac intensive care unit.

Aims: Left ventricular (LV) ventricular-arterial coupling (VAC) refers to the ratio of afterload (effective arterial elastance) to contractility (end-systolic elastance) as an integrated marker of cardiac performance. We sought to determine whether the echocardiographic VAC ratio, defined using the ratio of LV end-systolic volume (LVESV) to stroke volume (SV), predicted mortality in the cardiac intensive care unit (CICU).

Methods And Results: Mayo Clinic CICU patients from 2007 and 2018 were included.

Hemodynamics of Exercise-Induced Hypertension and Relationship to Outcomes in Adults With Coarctation of the Aorta.

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.

Temporal changes in prevalence and severity of pulmonary hypertension, and relationship to outcomes in coarctation of aorta.

Background: Pulmonary hypertension (PH) affects 20% of adults with coarctation of aorta (COA). What is not known is whether PH prevalence and severity increased over time, and the prognostic implications of such changes. The purpose of this study was to assess temporal changes in PH prevalence and severity (PH progression), and to determine the correlates and prognostic implications of pH progression in adults with COA.

Baseline characteristics of contemporary trial participants with heart failure and reduced ejection fraction: The VICTOR trial.

Aims: To describe the baseline characteristics of the participants in the VICTOR (Vericiguat Global Study in Patients with Chronic Heart Failure; NCT05093933) trial and compare them to recent trials in patients with heart failure and reduced ejection fraction (HFrEF).

Methods And Results: Baseline characteristics were evaluated in 6105 patients randomized to vericiguat or placebo. The mean age of the participants was 67 ± 11 years, 23.