Characterization and Application of Novel Exercise Recovery Patterns That Reflect Cardiac Performance: A Substudy of the SEQUOIA-HCM Trial.

Background: Post-exercise oxygen uptake recovery (VORec) is slow in advanced heart failure. We sought to establish easily derived VORec measures and evaluate their cardiospecificity and prognostic relevance in patients with dyspnea on exertion. We further sought to determine VORec modifiability proportional to changes in cardiac function with disease-specific treatment of obstructive hypertrophic cardiomyopathy.

Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy.

Background: Beta-blockers have been the initial treatment for symptomatic obstructive hypertrophic cardiomyopathy (HCM) despite limited evidence of their efficacy. Aficamten is a cardiac myosin inhibitor that reduces left ventricular outflow tract gradients, improves exercise capacity, and decreases HCM symptoms when added to standard medications. Whether aficamten as monotherapy provides greater clinical benefit than beta-blockers as monotherapy remains unknown.

Cardiopulmonary Exercise Testing for Characterization of Hypertrophic Cardiomyopathy: A Meta-Analysis.

Background: Hypertrophic cardiomyopathy (HCM) is associated with substantial risk of adverse cardiac events. Consequently, detailed physiologic assessment and accurate risk stratification in HCM are of high clinical importance. This systematic review and meta-analysis synthesizes current evidence on the utility of cardiopulmonary exercise testing (CPET) for characterization and prognostication of HCM.

Physiologic Phenotyping of Responses to Exercise and Activity in Heart Failure.

Subjective and objective limitations to exercise and activity are hallmarks of heart failure (HF), regardless of underlying ejection fraction (EF). These limitations relate to cardiovascular abnormalities involving the systolic and diastolic properties of the heart, venous, and arterial vasculature, as well as noncardiovascular abnormalities, including impairments in pulmonary function, autonomic regulation, anemia, metabolism, and changes in mitochondria and skeletal muscle. The contribution of these abnormalities varies between patients with HF with preserved EF and those with HF with reduced EF, but, even within each HF subtype, there is substantial individual patient pathophysiologic variability, which suggests a potentially important role for phenotyping based on exercise reserve responses to individualize treatment.

Transferrin Saturation Is a Better Predictor Than Ferritin of Metabolic and Hemodynamic Exercise Responses in HFpEF.

Background: Iron is a critical factor in cardiac function, oxygen carrying capacity in the blood, and mitochondrial function in skeletal muscle, all of which are key elements of oxygen uptake and utilization during exercise. However, the impact of iron status on hemodynamic responses to exercise and component variables of peak oxygen consumption in patients with heart failure with preserved ejection fraction (HFpEF) is unknown.

Objectives: The authors sought to determine the relationship between markers of iron status and comprehensive exercise response patterns and clinical outcomes in patients with HFpEF.

Blood Pressure Responses During Exercise Were Associated With Average Home Blood Pressure and Home Blood Pressure Variability: The Electronic Framingham Heart Study.

Background: Abnormal exercise blood pressure (BP) responses are associated with hypertension and cardiovascular disease, but their relationship with home BP over a mid- to long-term time span is unknown.

Methods: At an FHS (Framingham Heart Study) research examination (2016-2019), participants underwent maximum incremental ramp cycle ergometry cardiopulmonary exercise testing with BP measured every 2 minutes. At the same exam, English-speaking participants enrolled in the electronic FHS with an iPhone were provided with a digital BP cuff to measure home BP weekly for 1 year.

Trans-right ventricle metabolite gradients in obesity highlight multiple metabolic pathways.

Obesity and metabolic dysfunction are associated with pulmonary vascular remodeling, yet molecular mechanisms remain poorly understood. We sought to study trans-right ventricular (RV) metabolite gradients to elucidate potential molecular pathways operant among individuals with obesity and pulmonary hypertension. In this study, 38 individuals with obesity (mean age 58 years, 68% women, average BMI 36.

Sex Differences in Diabetic Cardiomyopathy and Treatment Response to AT-001: Insights From the ARISE-HF Study.

Background: Diabetic cardiomyopathy (DbCM) is a significant cause of heart failure (HF) in individuals with type 2 diabetes mellitus. Although sex differences are noted in HF patients, it is unclear if such differences exist in those with DbCM and whether sex-based differences affect treatment responses.

Objectives: This analysis focuses on sex differences in baseline characteristics of study participants with DbCM at high risk for progression to overt HF and sex-based treatment responses to high-dose AT-001, a novel aldose reductase inhibitor.

Health status in stage B heart failure from diabetic cardiomyopathy baseline results from ARISE-HF.

Aims: Assess the determinants of health status and its correlation with key parameters in individuals with diabetic cardiomyopathy (DbCM).

Methods: In the ARISE-HF trial, the Kansas City Cardiomyopathy Questionnaire (KCCQ), cardiopulmonary exercise testing (CPET), Physical Activity Scale for the Elderly (PASE) score, echocardiographic, and laboratory assessments were performed at baseline in 691 persons with DbCM.

Results: Study participants with lower KCCQ-Clinical Summary Score (CSS) were predominantly women, had poorer kidney function, higher body-mass index and natriuretic peptides, and lower hemoglobin levels.

Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial.

Importance: Excess body fat plays a pivotal role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). HU6 is a novel, controlled metabolic accelerator that enhances mitochondrial uncoupling resulting in increased metabolism and fat-specific weight loss.

Objective: To assess efficacy and safety of HU6 in reducing body weight, improving peak volume of oxygen consumption (VO2) and body composition among patients with obesity-related HFpEF.

Prediction and Longer-Term Outcomes of All-cause and Cardiovascular Mortality in the HEART-FID Trial.

Background: The HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose [FCM] as Treatment for Heart Failure with Iron Deficiency) is the largest trial to test intravenous iron (ferric carboxymaltose [FCM]) vs placebo in patients with heart failure and iron deficiency. The results showed a modest but nonstatistically significant reduction in important clinical outcomes, including all-cause mortality.

Objectives: We sought to understand the factors associated with all-cause mortality.

Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis.

Background: Objective indices of functional capacity in patients with diabetic cardiomyopathy and stage B heart failure (HF) have not been comprehensively defined. We sought to characterize the cardiopulmonary exercise characteristics of individuals with diabetic cardiomyopathy at high risk for overt HF.

Methods: The relationships from cardiopulmonary exercise testing with clinical and laboratory characteristics of participants with diabetic cardiomyopathy were evaluated using baseline data from the ARISE-HF trial (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure).

Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.

Background And Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD.

Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]).

Prognostic relevance of exercise pulmonary hypertension: results of the multicentre PEX-NET Clinical Research Collaboration.

Background: Exercise pulmonary hypertension (PH) was defined by a mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope >3 mmHg·min·L between rest and exercise in the 2022 European Society of Cardiology/European Respiratory Society PH guidelines. However, large, multicentre studies on the prognostic relevance of exercise haemodynamics and its added value to resting haemodynamics are missing.

Patients And Methods: The PEX-NET (Pulmonary Haemodynamics during Exercise Network) registry enrolled patients who underwent clinically indicated right heart catheterisations both at rest and ergometer exercise from 23 PH centres worldwide.

Cardiopulmonary Exercise Testing in Advanced Heart Failure Management.

Cardiopulmonary exercise testing (CPET) permits the assessment of gas exchange, electrocardiogram, and hemodynamic patterns throughout exercise, providing a window into multi-organ physiologic reserve during exercise. CPET provides risk stratification and informs management of advanced heart failure (HF). Increasingly, CPET is combined with echocardiography, or invasive right heart catheterization, which enables high-resolution assessment of cardiac and extracardiac limitations to exercise.

Early Renal Outcomes Following Heart Transplantation Using Organs Procured After Circulatory Death.

Background: Transplantation using hearts obtained through donation after circulatory death (DCD) is increasing, but data on recipient renal outcomes are limited.

Methods And Results: Patients at a single institution who underwent heart transplantation using organs procured through DCD or donation after brain death (DBD) from April 2016 to August 2022 were included in this retrospective cohort study. Hemodynamic measures were collected via right heart catheterization performed 1 week after transplantation.

Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

Background: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined.

Objectives: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten.

Effect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

Background: A primary goal in treating obstructive hypertrophic cardiomyopathy (oHCM) is to improve patients' health status: their symptoms, function, and quality of life. The health status benefits of aficamten, a novel cardiac myosin inhibitor, have not been comprehensively described.

Objectives: This study sought to determine the effect of aficamten on patient-reported health status, including symptoms of fatigue, shortness of breath, chest pain, physical and social limitations, and quality of life.