The benefits of cardiac rehabilitation (CR) have been demonstrated in patients after myocardial infarction (MI), and in patients with chronic heart failure (HF). The core components of the CR program include improvement in exercise tolerance and optimization of coronary risk factors (i.e., lipid and lipoprotein profiles, body weight, blood glucose levels, blood pressure levels, and smoking cessation). Indeed, CR has been shown to improve exercise capacity, control of cardiovascular risk factors, quality of life, hospital readmission, and mortality rates. Nonetheless, pre- and clinical CR and exercise training models are an enormous source of potential beneficial mechanisms that can be exploited for cardiac disease therapy. Consequently, in this review, we aim to explore the unique benefits of CR in HF and coronary artery disease, focusing on the epigenetic mechanisms involved and their translational relevance. These mechanisms may represent novel therapeutic targets to promote functional recovery after cardiac injury, and non-coding RNAs could be predictive biomarkers for CR success in patients.

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and poses significant treatment challenges due to its complex pathophysiology. Exercise training has emerged as a promising non-pharmacological intervention to improve outcomes in HFpEF patients. This study aims to evaluate the effect of exercise training on exercise tolerance, cardiac function and quality of life in HFpEF patients.

Through systematic review and meta-analysis, major databases were scoured for randomized controlled trials (RCTs) evaluating the influence of exercise training on HFpEF patients. Data on exercise tolerance, cardiac function parameters, and quality of life were extracted. The quality of the studies was assessed using the Cochrane Collaboration's risk of bias tool. Statistical analyses were performed using Review Manager 5.4, with mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (CIs) calculated for continuous variables.

Seven RCTs encompassing 470 participants met the inclusion criteria. Exercise training significantly improved exercise tolerance as measured by the 6-Minute Walk Test (P < 0.01) and peak VO₂ (P = 0.03). No significant effects were observed on cardiac function parameters, including the E/A ratio, E/e' ratio, and LVEF. Total quality of life was similar between exercise and control groups, but significantly enhanced in physical components about quality of life was observed in the exercise group (P = 0.03). There were no significant differences between high-intensity interval training (HIIT) and moderate continuous training (MCT) in improving exercise tolerance, cardiac function, or quality of life.

Exercise training effectively enhances exercise tolerance and physical quality of life in patients with HFpEF, without significantly impacting cardiac function parameters. HIIT and MCT has similar effect in HFpEF patients. These findings support the incorporation of exercise training into the management strategies for HFpEF patients to improve functional outcomes and quality of life.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing and prognosis remains poor, with a high risk of mortality or hospitalizations for worsening heart failure events. Apart from sodium-glucose cotransporter-2 inhibitors and diuretics, the management of HFpEF is nowadays based on the different aetiologies and cardiovascular or non-cardiovascular comorbidities. A great heterogeneity of clinical profiles has been described in HFpEF, with several recent studies focused on the identification of different HFpEF phenotypes. In this review, we summarize available evidence on phenotype profiling in HFpEF, describing the different phenotypes with the relative therapeutic implications, and reporting other specific clinical conditions relevant for HFpEF differential diagnosis.

Passive heat therapy is gaining popularity as an intervention to promote cardiovascular, physiological, and, to a lesser degree, thermoregulatory adaptations in patients with cardiovascular disease. Despite this, the efficacy of heat therapy to elicit these adaptations remains unknown. We searched five databases for original research, screening 2913 studies and identifying 18 eligible studies. Heat therapies included Waon therapy, balneotherapy, water perfused trousers, Finnish sauna, and foot immersion. Interventions were administered across various time frames (20-90 min) and performed 3-7 times per week, for durations of 2-8 weeks. The studies collectively involved a diverse population (mean age: 67 (10) years) with cardiovascular diseases. Heat therapy was consistently shown to improve ejection fraction, flow-mediated dilation, brain natriuretic peptide levels, New York Heart Association classification, and 6 min walk distance. However, positive effects on resting heart rate and blood pressure were infrequently observed, and thermoregulatory responses scarcely reported. Heat therapy may increase sweat rate during heat exposure and reduce resting core temperature, but adaptive skin blood flow responses were not observed. Passive heat therapy shows promising utility in patients with cardiovascular disease, while secondary benefits such as markers of thermoregulatory adaptation may also be observed, these require further investigation.

Long-term exercise intolerance and functional limitations are common after an episode of acute pulmonary embolism (PE), despite 3 to 6 months of anticoagulation. These persistent symptoms are reported in more than half of the patients with acute PE and are referred as "post-PE syndrome." Although these functional limitations can occur from persistent pulmonary vascular occlusion or pulmonary vascular remodeling, significant deconditioning can be a major contributing factor. Herein, the authors review the role of exercise testing to elucidate the mechanisms of exercise limitations to guide next steps in management and exercise training for musculoskeletal deconditioning.

Whilst metabolic inflexibility and substrate constraint have been observed in heart failure for many years, their exact causal role remains controversial. In parallel, many of our fundamental assumptions about cardiac fuel use are now being challenged like never before. For example, the emergence of sodium-glucose cotransporter 2 inhibitor therapy as one of the four 'pillars' of heart failure therapy is causing a revisit of metabolism as a key mechanism and therapeutic target in heart failure. Improvements in the field of cardiac metabolomics will lead to a far more granular understanding of the mechanisms underpinning normal and abnormal human cardiac fuel use, an appreciation of drug action, and novel therapeutic strategies. Technological advances and expanding biorepositories offer exciting opportunities to elucidate the novel aspects of these metabolic mechanisms. Methodologic advances include comprehensive and accurate substrate quantitation such as metabolomics and stable-isotope fluxomics, improved access to arterio-venous blood samples across the heart to determine fuel consumption and energy conversion, high quality cardiac tissue biopsies, biochemical analytics, and informatics. Pairing these technologies with recent discoveries in epigenetic regulation, mitochondrial dynamics, and organ-microbiome metabolic crosstalk will garner critical mechanistic insights in heart failure. In this state-of-the-art review, we focus on new metabolic insights, with an eye on emerging metabolic strategies for heart failure. Our synthesis of the field will be valuable for a diverse audience with an interest in cardiac metabolism.

Chronotropic incompetence (ChI) is linked with diminished exercise capacity in heart failure with preserved ejection fraction (HFpEF). Although exercise training has shown potential for improving functional capacity, the exercise modality associated with greater functional and chronotropic response (ChR) is not well-known. Additionally, how the ChR from different exercise modalities mediates functional improvement remains to be determined. This study aimed to evaluate the effect of three different exercise programs over current guideline recommendations on peak oxygen consumption (peakVO2) in patients with ChI HFpEF phenotype.

In this randomized clinical trial, 80 stable symptomatic patients with HFpEF and ChI (NYHA class II-III/IV) are randomized (1:1:1:1) to receive: a) a 12-week program of supervised aerobic training (AT), b) AT and low to moderate-intensity strength training, c)AT and moderate to high-intensity strength training, or d) guideline-based physical activity and exercise recommendations. The primary endpoint is 12-week changes in peakVO2. The secondary endpoints are 12-week changes in ChR, 12-week changes in quality of life, and how ChR changes mediate changes in peakVO2. A mixed-effects model for repeated measures will be used to compare endpoint changes. The mean age is 75.1 ± 7.2 years, and most patients are women (57.5 %) in New York Heart Association functional class II (68.7 %). The mean peakVO2, percent of predicted peakVO2, and ChR are 11.8 ± 2.6 mL/kg/min, 67.2 ± 14.7 %, and 0.39 ± 0.16, respectively. No significant baseline clinical differences between arms are found.

Training-HR will evaluate the effects of different exercise-based therapies on peakVO2, ChR, and quality of life in patients with ChI HFpEF phenotype.

ClinicalTrials.gov (NCT05649787).

[Purpose] To examine the effectiveness of acute and outpatient cardiac rehabilitation for severe intensive care unit (ICU)-acquired weakness. [Participant and Methods] A 79-year-old woman, diagnosed with takotsubo syndrome. A percutaneous catheter-based transvalvular left ventricular assist device was used from day 2 to day 8, extracorporeal membrane oxygenation from day 3 to day 9, and inotropic support from day 1 to day 15. The patient was weaned from the ventilator on day 59, transferred to another hospital on day 67, and discharged home on day 152. From days 16 to 65 and 177 to 262, she underwent inpatient rehabilitation and outpatient cardiac rehabilitation, respectively, at our hospital. [Results] After inpatient rehabilitation at our hospital, her Medical Research Council score improved from 16 to 46. In outpatient cardiac rehabilitation, her 6-minute walk distance improved from 385 to 473 m, and her Kansas City Cardiomyopathy Questionnaire score improved from 88.6 to 100. [Conclusion] The results suggest that acute rehabilitation can effectively improve muscle strength, whereas outpatient cardiac rehabilitation can effectively improve exercise tolerance and quality of life in patients with severe ICU-acquired weakness.

Heart failure with preserved ejection fraction (HFpEF) is a multifarious syndrome, accounting for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dysfunction seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from animal models and human myocardial tissues from failed hearts shows that mitochondrial aberrations cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodeling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of the recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and the associated signal molecules.

Diastolic dysfunction refers to impaired relaxation or filling of the ventricles during the diastolic phase of the cardiac cycle. Left ventricular diastolic dysfunction (LVDD) is common in hypertensive individuals and is associated with increased morbidity and mortality. LVDD serves as a critical precursor to heart failure, particularly heart failure with preserved ejection fraction. The pathophysiology of LVDD in hypertension is complex, involving alterations in cardiac structure and function, neurohormonal activation, and vascular stiffness. While the diagnosis of LVDD relies primarily on echocardiography, management remains challenging due to a lack of specific treatment guidelines for LVDD. This review offers an overview of the pathophysiological mechanisms underlying LVDD in hypertension, diagnostic methods, clinical manifestations, strategies for managing LVDD, and prospects for future research.

Heart failure and cancer remain 2 of the leading causes of morbidity and mortality, and the 2 disease entities are linked in a complex manner. Patients with cancer are at increased risk of cardiovascular complications related to the cancer therapies. The presence of cardiomyopathy or heart failure in a patient with new cancer diagnosis portends a high risk for adverse oncology and cardiovascular outcomes. With the rapid growth of cancer therapies, many of which interfere with cardiovascular homeostasis, heart failure practitioners need to be familiar with prevention, risk stratification, diagnosis, and management strategies in cardio-oncology. This Heart Failure Society of America statement addresses the complexities of heart failure care among patients with active cancer diagnoses and cancer survivors. Risk stratification, monitoring and management of cardiotoxicity are presented across stages A through D heart failure, with focused discussion on heart failure with preserved ejection fraction and special populations, such as survivors of childhood and young-adulthood cancers. We provide an overview of the shared risk factors between cancer and heart failure, highlighting heart failure as a form of cardiotoxicity associated with many different cancer therapeutics. Finally, we discuss disparities in the care of patients with cancer and cardiac disease and present a framework for a multidisciplinary-team approach and critical collaboration among heart failure, oncology, palliative care, pharmacy, and nursing teams in the management of these complex patients.

Myocardial stiffening naturally occurs with aging and contributes to diastolic dysfunction. Assessing myocardial stiffness non-invasively could improve the sensitivity of diastolic function evaluation in clinical practice. Shear wave (SW) elastography is a non-invasive tool for quantifying myocardial stiffness, where higher SW velocities indicate increased stiffness. We investigated whether SW elastography could detect differences in myocardial stiffness between athletes and sedentary non-athletes and, during exercise, reveal differences in operational stiffness that may indicate diastolic dysfunction.

We enrolled 20 master athletes (median age 60 [IQR 59-66] years) and 17 sedentary non-athletes (median age 58 [IQR 52-71] years). Standard exercise echocardiography revealed no significant differences in diastolic function between the groups. Additionally, ultra-high frame rate imaging was used to measure SW velocities after mitral valve closure (MVC) and aortic valve closure (AVC) at rest and during exercise. At rest, athletes had lower SW velocities after MVC compared to sedentary non-athletes (3.2 ± 0.4 m/s vs. 3.9 ± 0.7 m/s, respectively, P = 0.003). During exercise, SW velocities after AVC significantly increased in sedentary non-athletes but not in athletes (+1.6 ± 1.6 cm/s increase per 1% power output increase vs. 0.0 ± 0.8 cm/s, respectively, P = 0.006). An inverse correlation was found between the increase of SW velocity after AVC during exercise and VO2max (r = -0.51, P = 0.003).

SW elastography reveals reduced myocardial stiffness in athletes compared to sedentary non-athletes at rest and during exercise, which is not detected by conventional echocardiographic measurements. Exercise-induced changes in SW velocities after AVC may potentially serve as an early marker for detecting diastolic dysfunction.

The prevalence of HF with preserved ejection raction (HFpEF, with EF ≥50%) is increasing across all populations with high rates of hospitalization and mortality, reaching up to 80% and 50%, respectively, within a 5-year timeframe. Comorbidity-driven systemic inflammation is thought to cause coronary microvascular dysfunction and increased epicardial adipose tissue, leading to downstream friborsis and molecular changes in the cardiomyocyte, leading to increased stiffness and diastolic dynsfunction. HFpEF poses unique challenges in terms of diagnosis due to its complex and diverse nature. The diagnosis of HFpEF relies on a combination of clinical assessment, imaging studies, and biomarkers. An additional important step in diagnosing HFpEF involves excluding certain cardiac diagnoses that may be specific underlying causes of HFpEF or may be masquerading as HFpEF and require specific alternative treatment approaches. In addition to administering sodium-glucose cotransporter 2 inhibitors to all patients, the most effective approach to enhance clinical outcomes may involve tailored therapy based on each patient's unique clinical profile. Exercise should be recommended for all patients to improve the quality of life. Glucagon-like peptide-1 1 agonists are a promising treatment option in obese HFpEF patients. Novel approaches targeting inflammation are also in early phase trials.

Patients with different types of heart failure (HF) exhibit varying rates of blood flow through cardiac chambers and pressure gradients across the aortic valve, attributed to differing degrees of myocardial contractility. Assessment of these dynamics offers insights into early HF diagnosis. This study aimed to analyze left ventricular outflow tract (LVOT) blood flow parameters, specifically peak blood flow velocity and pressure gradient derived from four-dimensional flow cardiovascular magnetic resonance (4D flow CMR), and to evaluate 4D flow CMR's utility in distinguishing HF types.

This prospective cross-sectional study recruited 115 HF patients from January 2019 to May 2022 at the General Hospital of Ningxia Medical University, classified by the New York Heart Association Cardiac Function Classification of Heart Failure as class II-IV, alongside a control group (n=30). Participants underwent cardiovascular magnetic resonance (CMR), including 4D flow. HF patients were categorized into heart failure with reduced ejection fraction (HFrEF, n=55), heart failure with mildly reduced ejection fraction (HFmrEF, n=30), and heart failure with preserved ejection fraction (HFpEF, n=30), based on ejection fraction. The cardiac functional parameters and aortic valve flow indices were measured using Circle Cardiovascular Imaging. LVOT 4D flow data were obtained 3 mm below the junction of the aortic valve leaflets, assessing peak velocities above and below the valve. Differences in cardiac function and blood flow parameters between groups were analyzed using one-way analysis of variance (ANOVA). The accuracy of these parameters in identifying subgroups was assessed using the receiver operating characteristic (ROC) curve.

Analysis of conventional cardiac function parameters revealed that left ventricular ejection fraction (LVEF) was significantly lower in the HFrEF and HFmrEF groups compared to the HFpEF and control groups (P<0.01). Additionally, end-diastolic volume and end-systolic volume were significantly higher in the HFrEF and HFmrEF groups than in the HFpEF and control groups (P<0.01). However, there were no significant differences in cardiac function parameters between the HFpEF and control groups (P>0.05). Significant differences were observed in aortic valve peak pressure gradients (Supra-APGmax) among the four study groups (5.01±1.09 vs. 6.23±2.94 vs. 7.63±1.81 vs. 8.89±2.97 mmHg, P<0.05). Aortic valve peak velocities in the HFrEF group differed significantly from the HFpEF and control groups (111.31±12.05 cm/s vs. 137.2±16 vs. 147.15±24.55 cm/s, P<0.001). The ROC curve for the pressure gradient below the aortic valve had an area under the curve (AUC) of 0.728 [95% confidence interval (CI): 0.591-0.864, P=0.002], with an optimal threshold of 4.72 mmHg (sensitivity: 0.8, specificity: 0.7, Youden index: 0.5).

HF patients exhibit reduced pressure gradients across the aortic valve during systole, indicative of altered intracardiac blood flow dynamics. Combining aortic valve velocities and pressure gradients can aid in distinguishing different types of HF, including HFpEF patients.

Pulmonary hypertension (PH) is a major complication linked to adverse outcomes in heart failure with preserved ejection fraction (HFpEF), yet no specific therapies exist for PH associated with HFpEF (PH-HFpEF). We have recently reported on the role of skeletal muscle SIRT3 (sirtuin-3) in modulation of PH-HFpEF, suggesting a novel endocrine signaling pathway for skeletal muscle modulation of pulmonary vascular remodeling.

Using skeletal muscle-specific Sirt3 knockout mice (Sirt3skm-/-) and mass spectrometry-based comparative secretome analysis, we attempted to define the processes by which skeletal muscle SIRT3 defects affect pulmonary vascular health in PH-HFpEF.

Sirt3skm-/- mice exhibited reduced pulmonary vascular density accompanied by pulmonary vascular proliferative remodeling and elevated pulmonary pressures. Comparative analysis of secretome by mass spectrometry revealed elevated secretion levels of LOXL2 (lysyl oxidase homolog 2) in SIRT3-deficient skeletal muscle cells. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of Sirt3skm-/- mice, a rat model of PH-HFpEF, and humans with PH-HFpEF. In addition, expression levels of CNPY2 (canopy fibroblast growth factor signaling regulator 2), a known proliferative and angiogenic factor, were increased in pulmonary artery endothelial cells and pulmonary artery smooth muscle cells of Sirt3skm-/- mice and animal models of PH-HFpEF. CNPY2 levels were also higher in pulmonary artery smooth muscle cells of subjects with obesity compared with nonobese subjects. Moreover, treatment with recombinant LOXL2 protein promoted pulmonary artery endothelial cell migration/proliferation and pulmonary artery smooth muscle cell proliferation through regulation of CNPY2-p53 signaling. Last, skeletal muscle-specific Loxl2 deletion decreased pulmonary artery endothelial cell and pulmonary artery smooth muscle cell expression of CNPY2 and improved pulmonary pressures in mice with high-fat diet-induced PH-HFpEF.

This study demonstrates a systemic pathogenic impact of skeletal muscle SIRT3 deficiency in remote pulmonary vascular remodeling and PH-HFpEF. This study suggests a new endocrine signaling axis that links skeletal muscle health and SIRT3 deficiency to remote CNPY2 regulation in the pulmonary vasculature through myokine LOXL2. Our data also identify skeletal muscle SIRT3, myokine LOXL2, and CNPY2 as potential targets for the treatment of PH-HFpEF.

Exercise intolerance in heart failure arises from multifactorial pathophysiological mechanisms. Hepatokines, liver-synthesized molecules, regulate systemic metabolisms in peripheral tissues. We previously identified the hepatokine fetuin-A as being linked to liver hypoperfusion in heart failure. Here, we investigated the role of fetuin-A in connecting cardiac-hepatic-peripheral interaction.

We conducted a prospective study involving 202 consecutive hospitalized patients (mean age, 56.8 years; 76.2% men) with heart failure who underwent cardiopulmonary exercise testing. We measured the serum concentration of fetuin-A by ELISA. Correlation analysis revealed a negative association between fetuin-A levels and the ratio of minimum minute ventilation to carbon dioxide production, its slope, and a tendency toward a positive correlation with peak oxygen uptake. Patients with impaired exercise tolerance exhibited lower fetuin-A levels. During a median follow-up of 1045 days, 18.3% experienced cardiac events, including 4 cardiac deaths and 33 cases of worsening heart failure. Classification and regression tree analysis identified a high-risk subgroup with lower fetuin-A (<24.3 mg/L) and impaired exercise tolerance (peak oxygen uptake<14.2 mL/kg per min). Kaplan-Meier analysis revealed that this subgroup had the highest risk of cardiac events. In a multivariable Cox proportional hazard model, the combination of lower fetuin-A and exercise intolerance was independently associated with increased risks of cardiac events.

Reduced circulating fetuin-A levels were associated with exercise intolerance in heart failure patients. Fetuin-A could emerge as a target implicated in exercise capacity connecting cardiac-hepatic-peripheral interaction and as a valuable biomarker for predicting prognosis when combined with peak oxygen uptake.

Heart failure with preserved ejection fraction (HFpEF) remains a significant global health challenge, accounting for up to 50% of all heart failure cases and predominantly affecting the elderly and women. Despite advancements in therapeutic strategies, HFpEF's complexity poses substantial challenges in management, particularly due to its high comorbidity burden, including renal failure, atrial fibrillation, and obesity, among others. These comorbidities not only complicate the pathophysiology of HFpEF but also exacerbate its symptoms, necessitating a personalized approach to treatment focused on comorbidity management and symptom alleviation. In heart failure with reduced ejection fraction, exercise training (ET) was effective in improving exercise tolerance, quality of life, and reducing hospitalizations. However, the efficacy of ET in HFpEF patients remains less understood, with limited studies showing mixed results. Exercise intolerance is a key symptom in HFpEF patients, and it has a multifactorial origin since both central and peripheral oxygen mechanisms of transport and utilization are often compromised. Recent evidence underscores the potential of supervised ET in enhancing exercise tolerance and quality of life among HFpEF patients; however, the literature remains sparse and predominantly consists of small-scale studies. This review highlights the critical role of exercise intolerance in HFpEF and synthesizes current knowledge on the benefits of ET. It also calls for a deeper understanding and further research into exercise-based interventions and their underlying mechanisms, emphasizing the need for larger, well-designed studies to evaluate the effectiveness of ET in improving outcomes for HFpEF patients.

People receiving peritoneal dialysis may receive health benefits from physical activity or exercise. However, on-going uncertainty and fear regarding safety may result in this population missing out on the health benefits of participation. The aim of this study was to explore the characteristics and frequency of physical activity and/or exercise-related side effects (e.g., symptoms such as pain or shortness of breath) and negative health events (e.g., stroke or hyper/hypoglycemia) experienced by people receiving peritoneal dialysis.

An international online survey involving adults receiving peritoneal dialysis was conducted with questions related to nature, occurrence, and impact of side effects and/or negative health events experienced during or soon after participation in physical activity or exercise.

Fifty-two people completed the survey reporting 151 side effects that were related to physical activity and exercise and 67 that were possibly related. Fatigue (58% of respondents), muscle/joint soreness or pain (54%), and dizziness (43%) were the most frequently reported side-effect types. The majority occurred occasionally (58% of all side effects), if not rarely (24%) and participation in on-going physical activity or exercise was typically prevented only occasionally (39%) or not at all (31%). Side effects were mainly self-managed (54% of all side effects) or did not require treatment (19%) and had low (38%) or no effect (30%) on ability to do daily activities.

People receiving peritoneal dialysis generally experience side effects that can be considered a normal response to physical activity or exercise engagement. Furthermore, the risk of serious or peritoneal dialysis-specific side effects as a result of physical activity or exercise appears to be low. The results add to the emerging evidence suggesting physical activity and exercise appear to be safe for people receiving peritoneal dialysis.

Heart failure with preserved ejection fraction (HFpEF) has been characterized by lower blood flow to exercising limbs and lower peak oxygen utilization (V ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ), possibly associated with disease-related changes in sympathetic (α-adrenergic) signaling. Thus, in seven patients with HFpEF (70 ± 6 years, 3 female/4 male) and seven controls (CON) (66 ± 3 years, 3 female/4 male), we examined changes (%Δ) in leg blood flow (LBF, Doppler ultrasound) and legV ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ to intra-arterial infusion of phentolamine (PHEN, α-adrenergic antagonist) or phenylephrine (PE, α1-adrenergic agonist) at rest and during single-leg knee-extension exercise (0, 5 and 10 W). At rest, the PHEN-induced increase in LBF was not different between groups, but PE-induced reductions in LBF were lower in HFpEF (-16% ± 4% vs. -26% ± 5%, HFpEF vs. CON; P < 0.05). During exercise, the PHEN-induced increase in LBF was greater in HFpEF at 10 W (16% ± 8% vs. 8% ± 5%; P < 0.05). PHEN increased legV ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ in HFpEF (10% ± 3%, 11% ± 6%, 15% ± 7% at 0, 5 and 10 W; P < 0.05) but not in controls (-1% ± 9%, -4% ± 2%, -1% ± 5%; P = 0.24). The 'magnitude of sympatholysis' (PE-induced %Δ LBF at rest - PE-induced %Δ LBF during exercise) was lower in patients with HFpEF (-6% ± 4%, -6% ± 6%, -7% ± 5% vs. -13% ± 6%, -17% ± 5%, -20% ± 5% at 0, 5 and 10 W; P < 0.05) and was positively related to LBF, leg oxygen delivery, legV ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ , and the PHEN-induced increase in LBF (P < 0.05). Together, these data indicate that excessive α-adrenergic vasoconstriction restrains blood flow and limitsV ̇ O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ of the exercising leg in patients with HFpEF, and is related to impaired functional sympatholysis in this patient group. KEY POINTS: Sympathetic (α-adrenergic)-mediated vasoconstriction is exaggerated during exercise in patients with heart failure with preserved ejection fraction (HFpEF), which may contribute to limitations of blood flow, oxygen delivery and oxygen utilization in the exercising muscle. The ability to adequately attenuate α1-adrenergic vasoconstriction (i.e. functional sympatholysis) within the vasculature of the exercising muscle is impaired in patients with HFpEF. These observations extend our current understanding of HFpEF pathophysiology by implicating excessive α-adrenergic restraint and impaired functional sympatholysis as important contributors to disease-related impairments in exercising muscle blood flow and oxygen utilization in these patients.

Chronic heart failure (CHF) is characterized by dyspnea, exercise intolerance and impaired quality of life. Physical exercise is a key point in the treatment of these outcomes.

To evaluate the effect of 24 weeks of two different training strategies on functional capacity, muscle strength and quality of life in individuals with CHF.

The following tests and evaluations were performed before and after 24 weeks of training: exercise test, one-repetition maximum test (1- RM) and Minnesota Living with Heart Failure Questionnaire (MLHFQ). Subjects were randomized according to the modality they would perform first: aerobic training group (ATG - n=6) or strength training group (STG - n=7).

The sample consisted of 13 individuals (10 men), aged 55 ± 12 years and a left ventricular ejection fraction (LVEF) of 38.8 ± 5.3%. There was a significant increase in V'O 2peak only in STG (STG: 26.92 ± 9.81 vs 30.52 ± 8.39 mL.kg -1 .min -1 - p=0.025; ATG: 19.60 ± 7,00 vs 22.42 ± 8.54 mL.kg -1 .min -1 - p=0.119). Both groups showed significant improvements in muscle strength (STG: 45 ± 17 vs 51 ± 20 kg - p=0.001; ATG: 38 ± 19 vs 42 ± 20 kg - p=0.012). There was no significant difference in quality of life (STG: 30 ± 18 vs 24 ± 20 - p=0.109; ATG: 36 ± 16 vs 26 ± 15 - p=0.143).

The early implementation of strength training improves functional capacity and muscle strength of individuals with CHF.

Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality, and there are limited proven therapeutic strategies. Exercise has been shown to be beneficial in several studies. We aimed to evaluate the efficacy of exercise on functional, physiological, and quality-of-life measures.

A comprehensive search of Medline and Embase was performed. Randomized controlled trials (RCTs) of adult HFpEF patients with data on exercise intervention were included. Using meta-analysis, we produced pooled mean difference (MD) estimates with 95% confidence intervals (CIs) with Review Manager (RevMan) software for the peak oxygen uptake (VO2), Minnesota living with heart failure (MLWHF) and, other diastolic dysfunction scores. A total of 14 studies on 629 HFpEF patients were included (63.2% female) with a mean age of 68.1 years. Exercise was associated with a significant improvement in the peak VO2 (MD 1.96 mL/kg/min, 95% CI 1.25-2.68; P < 0.00001) and MLWHF score (MD -12.06, 95% CI -17.11 to -7.01; P < 0.00001) in HFpEF. Subgroup analysis showed a small but significant improvement in peak VO2 with high-intensity interval training (HIIT) vs. medium-intensity continuous exercise (MCT; MD 1.25 mL/kg/min, 95% CI 0.41-2.08, P = 0.003).

Exercise increases the exercise capacity and quality of life in HFpEF patients, and high-intensity exercise is associated with a small but statistically significant improvement in exercise capacity than moderate intensity. Further studies with larger participant populations and longer follow-up are needed to confirm these findings and elucidate potential differences between high- and medium-intensity exercise.

Patients with heart failure with preserved ejection fraction (HFpEF) commonly experience exercise intolerance, resulting in reduced cardiorespiratory fitness. This is characterised by a decreased maximal oxygen uptake (V̇O2peak), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO2). While exercise training has been shown to improve V̇O2peak in HFpEF patients, the effects on CO remain unclear. The aim of this study is to systematically review and analyse the current evidence on the effects of supervised exercise training on CO in patients with HFpEF.

We will systematically search for literature describing the effects of supervised exercise training on CO in patients with HFpEF. All eligible studies published before 30 June 2023 in the following electronic databases will be included: MEDLINE (Ovid), Embase (Ovid), SPORTDiscus (EBSCOhost), and CENTRAL (Cochrane Library). Effect sizes will be extracted for CO before and after a supervised exercise training intervention at rest and maximal exercise. Mass of heterogeneity (I2) will be calculated, and either fixed-effect models or random-effect models will be used for meta-analysis. To detect a potential publication bias, funnel plot analyses will be performed.

While several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O2peak, CO, and a-vDO2 are much scarcer, especially in patients with HFpEF. From a physiological perspective, measuring CO before and after supervised exercise training seems to be a reasonable way to accurately operationalise a potential improvement in cardiac function.

PROSPERO CRD42022361485.

Cancer therapy-related cardiac dysfunction (CTRCD) has been identified as a threat to overall and cancer-related survival. Although aerobic exercise training (AET) has been shown to improve cardiorespiratory fitness (CRF), the relationship between specific exercise regimens and cancer survival, heart failure development, and reduction of CTRCD is unclear. In this review, we discuss the impact of AET on molecular pathways and the current literature of sports in the field of cardio-oncology.

Cardio-oncological exercise trials have focused on variations of AET intensity by using moderate continuous and high intensity interval training, which are applicable, safe, and effective approaches to improve CRF. AET increases CRF, reduces cardiovascular morbidity and heart failure hospitalization and should thus be implemented as an adjunct to standard cancer therapy, although its long-term effect on CTRCD remains unknown. Despite modulating diverse molecular pathways, it remains unknown which exercise regimen, including variations of AET duration and frequency, is most suited to facilitate peripheral and central adaptations to exercise and improve survival in cancer patients.

The delivery of Cardiac Rehabilitation (CR) and attaining evidence-based treatment goals are challenging in developing countries, such as Malawi. The aims of this study were to (i) assess the effects of exercise training/ CR programme on cardiorespiratory and functional capacity of patients with chronic heart failure (CHF), and (ii) examine the effectiveness of a novel, hybrid CR delivery using integrated supervised hospital- and home-based caregiver approaches.

A pre-registered (UMIN000045380), randomised controlled trial of CR exercise therapy in patients with CHF was conducted between September 2021 and May 2022. Sixty CHF participants were randomly assigned into a parallel design-exercise therapy (ET) (n = 30) or standard of care (n = 30) groups. Resting hemodynamics, oxygen saturation, distance walked in six-minutes (6MWD) and estimated peak oxygen consumption (VO2 peak) constituted the outcome measures. The exercise group received supervised, group, circuit-based ET once weekly within the hospital setting and prescribed home-based exercise twice weekly for 12 weeks. Participants in both arms received a group-based, health behaviour change targeted education (usual care) at baseline, 8-, 12- and 16-weeks.

Most of the participants were female (57%) with a mean age of 51.9 ±15.7 years. Sixty-five percent (65%) were in New York Heart Association class III, mostly with preserved left ventricular ejection fraction (HFpEF) (mean Left Ventricular Ejection Fraction 52.9 ±10.6%). The 12-weeks ET led to significant reductions in resting haemodynamic measures (all P <0.05). The ET showed significantly higher improvements in the 6MWD (103.6 versus 13.9 m, p<0.001) and VO2 peak (3.0 versus 0.4 ml·kg-1·min-1, p <0.001). Significant improvements in 6MWD and VO2 peak (both p<0.001), in favour of ET, were also observed across all follow-up timepoints.

This novel, randomised, hybrid ET-based CR, delivered to mainly HFpEF patients using an integrated hospital- and home-based approach effectively improved exercise tolerance, cardiorespiratory fitness capacities and reduced perceived exertion in a resource-limited setting.

Heart failure (HF) represents a significant global health challenge that is still responsible for increasing morbidity and mortality despite advancements in pharmacological treatments. This review investigates the effectiveness of non-pharmacological interventions in the management of HF, examining lifestyle measures, physical activity, and the role of some electrical therapies such as catheter ablation, cardiac resynchronization therapy (CRT), and cardiac contractility modulation (CCM). Structured exercise training is a cornerstone in this field, demonstrating terrific improvements in functional status, quality of life, and mortality risk reduction, particularly in patients with HF with reduced ejection fraction (HFrEF). Catheter ablation for atrial fibrillation, premature ventricular beats, and ventricular tachycardia aids in improving left ventricular function by reducing arrhythmic burden. CRT remains a key intervention for selected HF patients, helping achieve left ventricular reverse remodeling and improving symptoms. Additionally, the emerging therapy of CCM provides a novel opportunity for patients who do not meet CRT criteria or are non-responders. Integrating non-pharmacological interventions such as digital health alongside specific medications is key for optimizing outcomes in HF management. It is imperative to tailor approaches to individual patients in this diverse patient population to maximize benefits. Further research is warranted to improve treatment strategies and enhance patient outcomes in HF management.

Heart failure with preserved ejection fraction (HFpEF) represents a prevalent and increasingly common condition. Recognized for its high incidence, there is a growing interest in exploring effective interventions, with exercise emerging as a critical component in the rehabilitation of HFpEF patients. We aim to update evidence on the impact of supervised exercise training on exercise capacity, diastolic function, arterial stiffness, and health-related quality of life (QoL) of individuals diagnosed with HFpEF.

We systematically reviewed the literature, searching from inception to December 2023, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. Statistical analyses utilized RevMan 5.4 with a random-effects model. Outcomes were presented as the weighted mean difference (WMD) alongside corresponding 95 % confidence intervals (CI), and heterogeneity was assessed using the I2 test.

Our final analysis included 7 randomized controlled trials (RCTs) of 346 participants, with an exercise follow-up duration of 12 to 48 weeks. In our pooled analysis, diastolic function, measured by E/A (WMD 0.01, 95 % CI: -0.04 to 0.05, p = 0.79; I2 = 0 %) and E/e' (WMD 0.87, 95 % CI: -11.09 to 12.83, p = 0.89; I2 = 69 %), showed no significant change post-exercise training. However, exercise capacity, measured by peak V̇o2 significantly improved (WMD 2.57, 95 % CI: 1.38 to 3.75, p < 0.0001; I2= 14 %). The QoL assessed by the Minnesota Living with Heart Failure (MLWHF) score remained unchanged (WMD -3.12, 95 % CI: -8.73 to 2.50, p = 0.28; I2 = 0 %), but the SF-36 physical functioning scale indicated significant improvement (WMD 9.84, 95 % CI: 2.94 to 16.73, p < 0.005; I2 = 0 %). Arterial stiffness and vascular function remained unaffected, as evidenced by arterial elastance (WMD -0.13, 95 % CI: -0.36 to 0.10, p = 0.26; I2 = 0 %) and total arterial compliance (WMD 0.12, 95 % CI: -0.26 to 0.49, p = 0.54; I2 = 0 %).

Exercise training is safe and significantly enhances exercise capacity and QoL in HFpEF, with no significant impact on diastolic function, arterial stiffness, or vascular function.

Heart failure with preserved ejection fraction (HFpEF) has a high prevalence, affecting more than 50% of patients with heart failure. HFpEF is associated with multiple comorbidities, and obesity is one of the most common. A distinct phenotype has been proposed for obese patients with HFpEF. Recent data show the beneficial role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss in diabetic and non-diabetic patients with obesity or overweight when given as adjunctive therapy to diet and exercise. The mechanisms of action are related to paracrine and endocrine signalling pathways within the gastrointestinal tract, pancreas, and central nervous system that delay gastric emptying, decrease appetite, augment pancreatic beta-cell insulin secretion, and suppress pancreatic glucagon release. These drugs are therefore potentially indicated for treatment of patients with HFpEF and obesity or overweight. Efficacy and safety need to be shown by clinical trials with a first one, Semaglutide Treatment Effect in People with obesity and heart failure with preserved ejection fraction (STEP HFpEF), recently concluded. The aim of the present review is to provide the pathophysiological and pharmacological rationale for GLP-1 RA administration to obese patients with HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine supplementation in both a primary and a secondary prevention approach on SKM function and factors modulating muscle function in an established HFpEF rat model. Female ZSF1 obese rats were randomized to an untreated, a primary prevention, and a secondary prevention group. For primary prevention, leucine supplementation was started before the onset of HFpEF (8 weeks of age) and for secondary prevention, leucine supplementation was started after the onset of HFpEF (20 weeks of age). SKM function was assessed at an age of 32 weeks, and SKM tissue was collected for the assessment of mitochondrial function and histological and molecular analyses. Leucine supplementation prevented the development of SKM dysfunction whereas it could not reverse it. In the primary prevention group, mitochondrial function improved and higher expressions of mitofilin, Mfn-2, Fis1, and miCK were evident in SKM. The expression of UCP3 was reduced whereas the mitochondrial content and markers for catabolism (MuRF1, MAFBx), muscle cross-sectional area, and SKM mass did not change. Our data show that leucine supplementation prevented the development of skeletal muscle dysfunction in a rat model of HFpEF, which may be mediated by improving mitochondrial function through modulating energy transfer.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.

Cancer and cardiovascular disease represent the two leading causes of morbidity and mortality worldwide. Women continue to enjoy a greater life expectancy than men. However, this comes at a cost with more women developing diabetes, hypertension and coronary artery disease as they age. These traditional cardiovascular risk factors not only increase their lifetime risk of heart failure but also their overall risk of cancer. In addition to this, many of the cancers with female preponderance are treated with potentially cardiotoxic therapies, adding to their increased risk of developing heart failure. As a result, we are faced with a higher risk population, potentially suffering from both cancer and heart failure simultaneously. This is of particular concern given the coexistence of heart failure and cancer can confer a worse prognosis than either a single diagnosis of heart failure or cancer alone. This review article explores the intersection of heart failure and cancer in women at multiple levels, including traditional cardiovascular risk factors, cardiovascular toxicity derived from antineoplastic and radiation therapy, shared pathophysiology and HF as an oncogenic process. This article further identifies opportunities and strategies for intervention and optimisation, whilst highlighting the need for contemporary guidelines to better inform clinical practice.

To investigate the association between leisure time physical activity (LTPA) and MRI-based diastolic function and the mediating role of metabolic health.

This cross-sectional analysis comprised 901 participants (46% women, mean age (SD): 56 (6) years (The Netherlands, 2008-2012)). LTPA was assessed via questionnaire, quantified in metabolic equivalent of tasks (METs)-minutes per week and participants underwent abdominal and cardiovascular MRI. Confirmatory factor analysis was used to construct the metabolic load factor. Piecewise structural equation model with adjustments for confounders was used to determine associations between LTPA and diastolic function and the mediating effect of metabolic load.

Significant differences in mitral early/late peak filling rate (E/A) ratio per SD of LTPA (men=1999, women=1870 MET-min/week) of 0.18, (95% CI= 0.03 to 0.33, p=0.021) were observed in men, but not in women: -0.01 (-0.01 to 0.34, p=0.058). Difference in deceleration time of mitral early filling (E-DT) was 0.13 (0.01 to 0.24, p=0.030) in men and 0.17 (0.05 to 0.28, p=0.005) in women. Metabolic load, including MRI-based visceral and subcutaneous adipose tissue, fasting glucose, high-density lipoprotein cholesterol and triglycerides, mediated these associations as follows: E/A-ratio of 0.030 (0.000 to 0.067, 19% mediated, p=0.047) in men but not in women: 0.058 (0.027 to 0.089, p<0.001) and E-DT not in men 0.004 (-0.012 to 0.021, p=0.602) but did in women 0.044 (0.013 to 0.057, 27% mediated, p=0.006).

A larger amount of LTPA was associated with improved diastolic function where confirmatory factor analysis-based metabolic load partly mediated this effect. Future studies should assess whether improving indicators of metabolic load alongside LTPA will benefit healthy diastolic function even more.

To determine whether nitrite can enhance exercise training (ET) effects in heart failure with preserved ejection fraction (HFpEF).

In this multicenter, double-blind, placebo-controlled, randomized trial conducted at 1 urban and 9 rural outreach centers between November 22, 2016, and December 9, 2021, patients with HFpEF underwent ET along with inorganic nitrite 40 mg or placebo 3 times daily. The primary end point was peak oxygen consumption (VO2). Secondary end points included Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS, range 0 to 100; higher scores reflect better health status), 6-minute walk distance, and actigraphy.

Of 92 patients randomized, 73 completed the trial because of protocol modifications necessitated by loss of drug availability. Most patients were older than 65 years (80%), were obese (75%), and lived in rural settings (63%). At baseline, median peak VO2 (14.1 mL·kg-1·min-1) and KCCQ-OSS (63.7) were severely reduced. Exercise training improved peak VO2 (+0.8 mL·kg-1·min-1; 95% CI, 0.3 to 1.2; P<.001) and KCCQ-OSS (+5.5; 95% CI, 2.5 to 8.6; P<.001). Nitrite was well tolerated, but treatment with nitrite did not affect the change in peak VO2 with ET (nitrite effect, -0.13; 95% CI, -1.03 to 0.76; P=.77) or KCCQ-OSS (-1.2; 95% CI, -7.2 to 4.9; P=.71). This pattern was consistent across other secondary outcomes.

For patients with HFpEF, ET administered for 12 weeks in a predominantly rural setting improved exercise capacity and health status, but compared with placebo, treatment with inorganic nitrite did not enhance the benefit from ET.

ClinicalTrials.gov identifier: NCT02713126.

Heart failure (HF) is a common cause of hospitalization and death, and the hallmark symptoms of HF, including dyspnea, fatigue, and exercise intolerance, contribute to poor patient quality of life (QoL). Cardiac rehabilitation (CR) is a comprehensive disease management program incorporating exercise training, cardiovascular risk factor management, and psychosocial support. CR has been demonstrated to effectively improve patient functional status and QoL among patients with HF. However, CR participation among patients with HF is poor. This review details the mechanisms of dyspnea and exercise intolerance among patients with HF, the physiologic and clinical improvements observed with CR, and the key components of a CR program for patients with HF. Furthermore, unmet needs and future strategies to improve patient participation and engagement in CR for HF are reviewed.

Studies have shown that the higher the aerobic capacity, the lower the risk of cardiovascular mortality and morbidity. In the case of cardiac patients, high-intensity interval training (HIIT) seems to be more effective than moderate-intensity continuous training (MICT) in improving aerobic capacity. The aim of this study was to investigate the effects of two community-based exercise programs using two short-term protocols (HIIT and MICT) on physical fitness and physical activity (PA) levels in coronary artery disease (CAD) patients. Methods. In this randomized controlled trial, body composition, aerobic capacity, muscle strength, and daily PA levels were assessed before and after 6 weeks of intervention in 69 patients diagnosed with CAD. All patients were randomly (1 : 1 : 1) assigned to two exercise groups (HIIT or MICT) or a control group (no exercise). Both training programs consisted of 6 weeks of supervised treadmill exercise, three sessions per week. MICT targeted ≈70-75% of peak heart rate (HR), while HIIT aimed for ≈85-95% of peak HR. The control group only followed the medical recommendations. Results. Community-based exercise programs showed more positive effects on physical fitness variables and physical activity levels compared to control. HIIT could significantly improve waist circumference, body fat mass, VO2peak, sedentary behavior, and moderate-to-vigorous PA compared to MICT. Moreover, the control group showed poorer results. Conclusion. HIIT can improve health outcomes more positively than MICT and control. These findings indicate that HIIT may be an alternative and effective training method in community-based exercise programs for CAD patients. This trial is registered with NCT03538119.