Comparison of exercise training modalities and change in peak oxygen consumption in heart failure with preserved ejection fraction: a secondary analysis of the OptimEx-Clin trial.

Aims: Exercise training (ET) is an effective therapy in heart failure with preserved ejection fraction (HFpEF), but the influence of different ET characteristics is unclear. We aimed to evaluate the associations between ET frequency, duration, intensity [% heart rate reserve (%HRR)] and estimated energy expenditure (EEE) with the change in peak oxygen consumption (V̇O2) over 3 months of moderate continuous training (MCT, 5×/week) or high-intensity interval training (HIIT, 3×/week) in HFpEF.

Methods And Results: ET duration and heart rate (HR) were recorded with a smartphone application.

Empagliflozin Improves Diastolic Function in HFpEF by Restabilizing the Mitochondrial Respiratory Chain.

Background: Clinical studies demonstrated beneficial effects of sodium-glucose-transporter 2 inhibitors on the risk of cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF). However, underlying processes for cardioprotection remain unclear. The present study focused on the impact of empagliflozin (Empa) on myocardial function in a rat model with established HFpEF and analyzed underlying molecular mechanisms.

Locomotor and respiratory muscle abnormalities in HFrEF and HFpEF.

Heart failure (HF) is a chronic and progressive syndrome affecting worldwide billions of patients. Exercise intolerance and early fatigue are hallmarks of HF patients either with a reduced (HFrEF) or a preserved (HFpEF) ejection fraction. Alterations of the skeletal muscle contribute to exercise intolerance in HF.

Baroreflex activation therapy in patients with heart failure with reduced ejection fraction: a single-centre experience.

Aims: Heart failure with reduced ejection fraction (HFrEF) is associated with excessive sympathetic and impaired parasympathetic activity. The Barostim Neo™ device is used for electronical baroreflex activation therapy (BAT) to counteract autonomic nervous system dysbalance. Randomized trials have shown that BAT improves walking distance and reduces N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels at least in patients with only moderate elevation at baseline.

Impact of educational attainment on preventive efforts after myocardial infarction: results of the IPP and NET-IPP trials.

Aims: Educational attainment might impact secondary prevention after myocardial infarction (MI). The purpose of the present study was to compare the rate of risk factors and the efficacy of an intensive prevention program (IPP), performed by prevention assistants and supervised by physicians, in patients with MI and different levels of education.

Methods: In this post hoc analysis of the multicenter IPP and NET-IPP trials, patients with MI were stratified into two groups according to educational attainment: no "Abitur" (no A) vs.

Use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

Aims: Despite its high incidence and mortality risk, there is no evidence-based treatment for non-ischaemic cardiogenic shock (CS). The aim of this study was to evaluate the use of mechanical circulatory support (MCS) for non-ischaemic CS treatment.

Methods And Results: In this multicentre, international, retrospective study, data from 890 patients with non-ischaemic CS, defined as CS due to severe de-novo or acute-on-chronic heart failure with no need for urgent revascularization, treated with or without active MCS, were collected.

Trajectory and correlates of pulmonary congestion by lung ultrasound in patients with acute myocardial infarction: insights from PARADISE-MI.

Aim: PARADISE-MI examined the efficacy of sacubitril/valsartan in acute myocardial infarction (AMI) complicated by reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both. We sought to assess the trajectory of pulmonary congestion using lung ultrasound (LUS) and its association with cardiac structure and function in a pre-specified substudy.

Methods And Results: Patients without prior heart failure (HF) underwent eight-zone LUS and echocardiography at baseline (±2 days of randomization) and after 8 months.

Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model.

Besides structural alterations in the myocardium, heart failure with preserved ejection fraction (HFpEF) is also associated with molecular and physiological alterations of the peripheral skeletal muscles (SKM) contributing to exercise intolerance often seen in HFpEF patients. Recently, the use of Sodium-Glucose-Transporter 2 inhibitors (SGLT2i) in clinical studies provided evidence for a significant reduction in the combined risk of cardiovascular death or hospitalization for HFpEF. The present study aimed to further elucidate the impact of Empagliflozin (Empa) on: (1) SKM function and metabolism and (2) mitochondrial function in an established HFpEF rat model.

Impact of Different Training Modalities on Molecular Alterations in Skeletal Muscle of Patients With Heart Failure With Preserved Ejection Fraction: A Substudy of the OptimEx Trial.

Background: Exercise intolerance is a cardinal feature of heart failure with preserved ejection fraction and so far exercise training (ET) is the most effective treatment. Since the improvement in exercise capacity is only weakly associated with changes in diastolic function other mechanisms, like changes in the skeletal muscle, contribute to improvement in peak oxygen consumption. The aim of the present study was to analyze molecular changes in skeletal muscle of patients with heart failure with preserved ejection fraction performing different ET modalities.

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction: Differences between ischemic and non-ischemic etiology.

Background: Exercise for heart failure (HF) with reduced ejection fraction (HFrEF) is recommended by guidelines, but exercise mode and intensities are not differentiated between HF etiologies. We, therefore, investigated the effect of moderate or high intensity exercise on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and maximal exercise capacity (peak VO) in patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM).

Methods: The Study of Myocardial Recovery after Exercise Training in Heart Failure (SMARTEX-HF) consecutively enrolled 231 patients with HFrEF (LVEF ≤ 35 %, NYHA II-III) in a 12-weeks supervised exercise program.

Cardiovascular risk factors, exercise capacity and health literacy in patients with chronic ischaemic heart disease and type 2 diabetes mellitus in Germany: Baseline characteristics of the Lifestyle Intervention in Chronic Ischaemic Heart Disease and Type 2 Diabetes study.

Background: Lifestyle interventions are a cornerstone in the treatment of chronic ischaemic heart disease (CIHD) and type 2 diabetes mellitus (T2DM). This study aimed at identifying differences in clinical characteristics between categories of the common lifestyle intervention targets BMI, exercise capacity (peak V̇O) and health literacy (HL).

Methods: Cross-sectional baseline characteristics of patients enrolled in the LeIKD trial (Clinicaltrials.

Peak O -pulse predicts exercise training-induced changes in peak V̇O in heart failure with preserved ejection fraction.

Aims: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O ) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter-individual responses vary significantly. Because it is unlikely that ET-induced improvements in peak V̇O are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O -pulse (V̇O  × HR , reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O , is inversely associated with the change in peak V̇O (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF.

Methods And Results: This was a secondary analysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON).

Impact of different training modalities on high-density lipoprotein function in HFpEF patients: a substudy of the OptimEx trial.

Aims: In heart failure with preserved ejection fraction (HFpEF), the reduction of nitric oxide (NO)-bioavailability and consequently endothelial dysfunction leads to LV stiffness and diastolic dysfunction of the heart. Besides shear stress, high-density lipoprotein (HDL) stimulates endothelial cells to increased production of NO via phosphorylation of endothelial nitric oxide synthase (eNOS). For patients with heart failure with reduced ejection fraction, earlier studies demonstrated a positive impact of exercise training (ET) on HDL-mediated eNOS activation.

Targeting MuRF1 by small molecules in a HFpEF rat model improves myocardial diastolic function and skeletal muscle contractility.

Background: About half of heart failure (HF) patients, while having preserved left ventricular function, suffer from diastolic dysfunction (so-called HFpEF). No specific therapeutics are available for HFpEF in contrast to HF where reduced ejection fractions (HFrEF) can be treated pharmacologically. Myocardial titin filament stiffening, endothelial dysfunction, and skeletal muscle (SKM) myopathy are suspected to contribute to HFpEF genesis.

Iron Deficiency Impacts Diastolic Function, Aerobic Exercise Capacity, and Patient Phenotyping in Heart Failure With Preserved Ejection Fraction: A Subanalysis of the OptimEx-Clin Study.

Aims: Iron deficiency (ID) is linked to reduced aerobic exercise capacity and poor prognosis in patients with heart failure (HF) with reduced ejection fraction (HFrEF); however, data for HF with preserved ejection fraction (HFpEF) is scarce. We assessed the relationship between iron status and diastolic dysfunction as well as aerobic exercise capacity in HFpEF, and the contribution of iron status to patient phenotyping.

Methods And Results: Among 180 patients with HFpEF (66% women; median age, 71 years) recruited for the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx-Clin) trial, baseline iron status, including iron, ferritin, and transferrin saturation, was analyzed ( = 169) in addition to exercise capacity (peak oxygen uptake [peak V̇O]) and diastolic function (E/e').

A randomized clinical trial on the short-term effects of 12-week sacubitril/valsartan vs. enalapril on peak oxygen consumption in patients with heart failure with reduced ejection fraction: results from the ACTIVITY-HF study.

Aims: ACTIVITY-HF was a randomized, double-blind, active-controlled study, which assessed the short-term effect of sacubitril/valsartan compared with the active comparator enalapril on improving maximal exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF).

Methods And Results: A total of 201 ambulatory patients with HFrEF (left ventricular ejection fraction ≤ 40%, New York Heart Association class III) across 34 centres in Germany were randomized (1:1) to receive sacubitril/valsartan 97/103 mg bid (n = 103) or enalapril 10 mg bid (n = 98). The primary endpoint of the study was the change from baseline in peak oxygen consumption (VO ; adjusted to body weight) after 12 weeks, and the key secondary endpoint was change from baseline in peak VO after 6 weeks.

miR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: an analysis of the OptimEx-Clin trial.

Aims: In patients with heart failure with preserved ejection fraction (HFpEF), exercise training improves the quality of life and aerobic capacity (peakV·O2). Up to 55% of HF patients, however, show no increase in peakV·O2 despite adequate training. We hypothesized that circulating microRNAs (miRNAs) can distinguish exercise low responders (LR) from exercise high responders (HR) among HFpEF patients.

Ubiquitin-proteasome-system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF.

Background: Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin-proteasome-system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing.

Sacubitril/Valsartan Improves Diastolic Function But Not Skeletal Muscle Function in a Rat Model of HFpEF.

The angiotensin receptor/neprilysin inhibitor Sacubitril/Valsartan (Sac/Val) has been shown to be beneficial in patients suffering from heart failure with reduced ejection fraction (HFrEF). However, the impact of Sac/Val in patients presenting with heart failure with preserved ejection fraction (HFpEF) is not yet clearly resolved. The present study aimed to reveal the influence of the drug on the functionality of the myocardium, the skeletal muscle, and the vasculature in a rat model of HFpEF.

Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial.

Importance: Endurance exercise is effective in improving peak oxygen consumption (peak V̇o2) in patients with heart failure with preserved ejection fraction (HFpEF). However, it remains unknown whether differing modes of exercise have different effects.

Objective: To determine whether high-intensity interval training, moderate continuous training, and guideline-based advice on physical activity have different effects on change in peak V̇o2 in patients with HFpEF.

Molecular Mechanisms of Diaphragm Myopathy in Humans With Severe Heart Failure.

[Figure: see text].