Improve Exercise Tolerance Research Articles

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH. Herein, we evaluated in a murine model of hemolysis driven SCD-PH, if intrapulmonary Hpx administration bi-weekly for 10 weeks improves lung iron deposition, exercise tolerance, cardiovascular function, and multi-omic indices associated with SCD-PH. Data shows Hpx delivered with a micro-sprayer deposits Hpx in the alveolar regions. Hpx extravasates into the perivascular compartments but does not diffuse into the circulation. Histological examination shows Hpx therapy decreased lung iron deposition, 4-HNE, and HO-1 expression. This was associated with improved exercise tolerance, cardiopulmonary function, and multi-omic profile of whole lung and RV tissue. Our data provides proof of concept that treating lung heme-iron by direct administration of Hpx to the lung attenuates the progression of PH associated with SCD.

Exploring patient perspectives of barriers and facilitators to participating in hospital-based pulmonary rehabilitation in patients diagnosed with non-small-cell lung cancer treated with curative intent.

Pulmonary rehabilitation (PR) is increasingly offered to patients who have undergone lung resection for non-small-cell lung carcinoma (NSCLC) as it can improve exercise tolerance and quality of life. However, designing and implementing such a complex multidisciplinary programme has its challenges. This study aims to explore perspectives of patients offered PR services post-lung resection for NSCLC to gain an understanding of the potential barriers and facilitators behind implementing and designing PR programmes. The PR programmes were offered in an outpatient rehabilitation gym at University Hospital Limerick, Ireland. Patients attending routine follow-up appointments post-lung cancer resection during the period of the study were identified and based on inclusion criteria were invited to participate in semi-structured interviews (focus groups). Interviews with patients who participated in the PR programme (n = 8) and those who declined (n = 4) were transcribed and major themes identified using normalisation process theory (NPT analysis) before interpretation of the themes in context. Across 4 focus groups that were conducted, the important barriers identified were the presence of comorbidities, location, perceived lack of benefit, and a fear of causing harm. Relevant facilitators included the prospect of acquiring new knowledge, optional access to psychological support, peer interaction/social support, individualised, tailored programmes, and a holistic approach to recovery as well as goal setting and accomplishment. Patient participation in PR has been shown to be influenced by both external and intrapersonal variables. The barriers and facilitators experienced by the patients in this study contribute to the existing knowledge of the patient experience of pulmonary rehabilitation and can help to inform clinical practice and future research.

Different effects of catheter ablation on exercise tolerance, leg strength, and quality of life in paroxysmal versus persistent atrial fibrillation.

Catheter ablation (CA) can improve exercise tolerance and quality of life (QOL) in patients with atrial fibrillation (AF). However, its differential effects on muscle strength between paroxysmal AF (PAF) and nonparoxysmal AF (Non-PAF) remain unclear. We evaluated 94 patients (67.8 ± 10.3 years old, 71% male) who underwent CA (PAF/Non-PAF 46/48) without AF recurrence. Six-minute walk distance (6MWD), leg strength, and an AF-specific QOL questionnaire (AFQLQ) were evaluated at baseline, 3, and 6 months after CA. At baseline, the 6MWD and AFQLQ subset 3 score were significantly lower in patients with PAF than in those with Non-PAF, but the parameters of muscle strength were comparable between the two groups. Both 6MWD and AFQLQ significantly improved at 6 months after CA in both groups. However, leg strength at 6 months after CA significantly improved in the Non-PAF group (54.9 ± 16.5 to 58.4 ± 15.2, p < .05) but not in the PAF group. Successful CA for both PAF and Non-PAF improved QOL and exercise tolerance. Additionally, CA improved leg strength in Non-PAF patients.

Efficacy of Telerehabilitation Protocols for Improving Functionality in Post-COVID-19 Patients.

Telerehabilitation is essential for the recovery of post-COVID-19 patients, improving exercise tolerance, dyspnea, functional capacity, and daily activity performance. This study aimed to describe telerehabilitation protocols specifically designed for individuals with post-COVID-19 sequelae. A systematic review was conducted with registration number CRD42023423678, based on searches developed in the following databases: ScienceDirect, Scopus, Dimensions.ai and PubMed, using keywords such as "telerehabilitation" and "COVID-19". The final search date was July 2024. The selection of studies involved an initial calibration process, followed by independent filtering by the researchers. The selection criteria were applied prior to critical appraisal, data extraction, and the risk of bias assessment. After reviewing 405 full-text papers, 14 articles were included that focused on telerehabilitation interventions for post-COVID-19 patients. These interventions were designed for remote delivery and included exercise protocols, vital sign monitoring, and virtual supervision by physical therapists. The studies reported improvements in physical function, muscle performance, lung capacity, and psychological outcomes. Significant gains were observed in strength, mobility, and functional capacity, as well as reductions in dyspnea, fatigue, and improvements in quality of life, particularly in social domains. Intervention protocols included aerobic, strength, and respiratory exercises, monitored using tools such as heart rate monitors and smartphones. Telerehabilitation positively impacts lung volumes, pulmonary capacities, dyspnea reduction, functionality, muscle performance, and independence in post-COVID-19 patients.

L-Arginine supplementation as mitochondrial therapy in diabetic cardiomyopathy

In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated with a high risk of mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are the first signs of DC. The underlying mechanisms are not fully elucidated, and there is an urgent need for specific biomarkers and molecular targets for early diagnosis and treatment. Mitochondrial alterations play a key role in the development of DC, and microRNAs regulating mitochondrial function are emerging as potential biomarkers of metabolic stress in DC. L-Arginine (Arg) supplementation has been shown to be an effective strategy for improving mitochondrial function and energetics, with a significant impact on physical performance. The aim of the current study was to evaluate the effects of Arg supplementation on cardiac mitochondrial function, DC development, and relative phenotypes including exercise intolerance. We used db/db mice as a model of type II diabetes, chronically treated with Arg (1 mg/kg/day) for 12 weeks. Arg-treated db/db mice showed preserved diastolic function and left ventricular morphology compared with untreated diabetic mice. Arg supplementation also improved exercise tolerance and the propensity to physical activity. Mitochondrial respiration was significantly increased in cardiomyocytes isolated from treated db/db mice, as well as in diabetic cardiomyocytes treated with Arg in vitro. The improvement of cardiac mitochondrial function in db/db + Arg mice was associated with an increase in PGC-1-alpha levels, mitochondrial biogenesis, recycling, and antioxidant capacity. Arg treatment prevented the accumulation of circulating and cardiac miR-143 in db/db mice, which is an index of metabolic stress and activation of mitochondrial damage mechanisms. In conclusion, Arg supplementation is effective in preventing the development of DC, preserving diastolic function and exercise tolerance by improving mitochondrial fitness and homeostasis. Additionally, miR-143 could potentially be employed to monitor cardiac metabolic stress and the effects of Arg treatment in diabetes.

Paradoxical improvement in exercise tolerance and peak VO2 consumption after treatment with ivabradine and beta-blockers in a patient with mild dilated cardiomyopathy and inappropriate sinus tachycardia—a case report

Abstract Background Left bundle branch block (LBBB) is a rare conduction disorder in athletes associated with ventricular dyssynchrony, which can lead to left ventricular systolic dysfunction and exercise intolerance. Inappropriate sinus tachycardia (IST) is characterized by an excessive heart rate (HR) that is not related to physiological needs, often resulting in reduced exercise capacity. Managing these conditions in athletes can be challenging, as standard treatments like beta-blockers and ivabradine, while effective in controlling HR, are described to be associated with a reduction in maximal exercise performance. Case summary A 50-year-old amateur athlete presented with exercise intolerance, LBBB, and mild dilated cardiomyopathy due to ventricular dyssynchrony. Resting electrocardiogram and 24-h monitoring confirmed IST. Initial cardiopulmonary exercise testing (CPET) off-therapy showed rapid HR increase during exertion, an early plateau in oxygen pulse, and reduced peak oxygen consumption (VO2, 22.1 mL/kg/min, 76% of the predicted value). After 1 month of ivabradine 5 mg b.i.d., there was some improvement in these parameters. At the third follow-up, with combined therapy of ivabradine (5 mg b.i.d.) and metoprolol (50 mg b.i.d.), the HR response during exercise normalized, and CPET parameters significantly improved, with peak VO2 reaching 29.2 mL/kg/min (101% of the predicted value). Discussion This case highlights a paradoxical improvement in exercise tolerance and peak VO2 with combined ivabradine and beta-blocker therapy in a patient with IST. The treatment optimized the HR response during exercise, suggesting that individualized strategies can enhance exercise performance in patients with IST and mild cardiomyopathy, despite the expected limitations of these medications.

A single-blind randomized trial comparing penetrating needles and non-penetrating needles with electrical stimulation combined with exercise training for relief of dyspnea and improving exercise tolerance in chronic obstructive pulmonary disease patients

A single-blind randomized trial comparing penetrating needles and non-penetrating needles with electrical stimulation combined with exercise training for relief of dyspnea and improving exercise tolerance in chronic obstructive pulmonary disease patients

Surgical Explantation of an Amplatzer Device for Patent Foramen Ovale Closure in a Patient With Nickel Allergy: A Case Report.

Patent foramen ovale (PFO) closure using percutaneous devices, such as the Amplatzer occluder, is a common treatment for patients with a history of cryptogenic stroke or transient ischemic attack (TIA). Although generally well-tolerated, some patients may develop adverse reactions to the device materials, particularly in the presence of a nickel allergy. Symptoms can include chest pain, rashes, and migraines, which may necessitate surgical removal of the device. In such cases, careful surgical planning and execution are essential to ensure successful outcomes and symptom resolution. We present the case of a 39-year-old female with existing PFO closure using an Amplatzer device, who developed severe, persistent atypical chest pain radiating to her upper extremities and occasional migraines 1 month after Amplatzer implantation. Patch testing confirmed a nickel allergy, prompting a referral to our service for surgical explantation of the device. The patient underwent Amplatzer device removal and reconstruction of the interatrial septum via sternotomy. The surgical technique involved meticulous excision of the device while preserving maximal septal tissue, allowing for primary closure of the interatrial septum without the need for a pericardial patch. Intraoperatively, significant scar tissue and inflammation were observed surrounding the device and atrial septal tissue, necessitating careful excision while preserving healthy tissue. The left atrial appendage was oversewn using a polypropylene suture for thromboembolism prophylaxis. Amniotic membrane allograft and autologous platelet-rich plasma were applied to promote wound healing, with specialized suture tapes used for chest closure to avoid using stainless steel sternal wires (the most common alloy, 316 L surgical steel contains around 15% nickel) and minimize the risk of sternal complications. The patient tolerated the procedure well, with complete resolution of symptoms following device removal. At follow-up, she reported improved exercise tolerance, enhanced quality of life, and was able to discontinue her pregabalin medication after 30 months of use (600 mg once daily). She returned to work with light duties 6 weeks postoperatively. This case highlights the importance of preoperative allergy testing to consider nickel allergy in patients before implanting devices such as an Amplatzer, as well as after considering de novo nickel sensitization as a potential cause when such symptoms develop after implantation. This case also highlights the value of surgical intervention in alleviating symptoms and optimizing patient outcomes in cases of device-related complications.

Effectiveness of acupuncture as an adjunct to cardiac rehabilitation after coronary artery bypass grafting.

Considering the importance of cardiac rehabilitation after coronary artery bypass grafting (CABG) and the development of acupuncture over the past few decades, the aim of this study was to evaluate the effects of acupuncture on patients' exercise tolerance, heart rate and blood pressure after CABG. Thirty-four patients with a history of recent CABG were recruited between 2019 and 2020 for this clinical trial and randomly divided into two groups receiving acupuncture plus cardiac rehabilitation (group A) and cardiac rehabilitation alone (group B). In both groups, exercise-based rehabilitation exercise was performed. Group A additionally received acupuncture at PC6, PC4, HT7 and GB20 bilaterally. Changes in blood pressure, heart rate and Borg scale score were evaluated before, during and after the course of the treatment. Heart rate was significantly lower in group A compared to group B after completion of the course of the treatment (P = 0.022). However, there were no statistically significant differences between the two groups in systolic or diastolic blood pressure or Borg scale scores (P > 0.05). Nevertheless, the Borg scale scores showed a significant decrease within each group over time (P < 0.001), reflecting an improvement in the patients' ability to tolerate activity after cardiac rehabilitation with or without acupuncture. Acupuncture in combination with exercise-based cardiac rehabilitation was more effective at decreasing heart rate than cardiac rehabilitation alone after CABG. Both approaches appeared to be similarly effective at improving exercise tolerance. In this study, the addition of acupuncture at the aforementioned traditional acupuncture point locations to exercise-based cardiac rehabilitation did not affect blood pressure. IRCT20171208037793N1 (Iranian Registry of Clinical Trials).

Effects of intermittent hypoxia exposures and interval hypoxic training on exercise tolerance (narrative review)

The ability to perform steady-state submaximal exercise at a certain intensity (exercise tolerance) predicts endurance performance in athletes, but also the quality of life and the capability to perform daily living activities in older people and patients suffering from chronic diseases. Improvements in exercise tolerance following exercise training are well established but may also occur or be enhanced as a consequence of adaptations to other stimuli, e.g., repeated exposures to real or simulated altitude. Adaptive responses (i.e., beneficially impacting exercise tolerance) depend on the type and extent of hypoxia stimuli, in particular, whether they are applied during exercise (intermittent hypoxia training, IHT) or at rest (intermittent hypoxia exposure, IHE).This brief review summarizes the evidence showing that IHT seems to elicit more pronounced effects on exercise tolerance than IHE. The most relevant adaptations to IHT are primarily provoked within the working skeletal muscles, whereas the rather small effects of IHE may include improved autonomic regulatory processes, endothelial function, cardioprotection, and increasing antioxidant capacity, all of which can probably be enhanced by combination with exercise (IHT). While IHE seems particularly suited for sedentary and elderly people or those suffering from chronic diseases, IHT will be more appropriate for young and already trained people. Thus, IHE is recommended for those with low exercise tolerance and can be followed up with exercise training in normoxia and finally with IHT.

Evidence of Cardiac Rehabilitation for Heart Failure With Reduced Ejection Fraction in Recovery to Maintenance Phase.

Heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) is typically coupled with progressive left ventricular enlargement and detrimental cardiac remodeling. The management of HFrEF is comprehensive and primarily involves pharmacologic treatment using cardioprotective agents. Cardiac rehabilitation (CR) is also strongly recommended as a treatment for HFrEF. The evidence on CR for HFrEF is accumulating. CR improves exercise tolerance, subjective symptoms caused by HF, quality of life, and rehospitalization rates. Furthermore, CR may improve all-cause mortality, although the improvement might not be evident in the short term (<1 year) but could potentially become more apparent over a longer period. In the upcoming era of super-aging and advancements in information and communications technology, CR for HFrEF will also require updating. Further research on exercise therapy will require a comprehensive evaluation of the quality and nature of exercise and whether CR would be conducted in a home-based or remote setting; these studies should include older adults, and the findings have the potential to revolutionize the field of CR.

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p&lt;0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Efficacy and safety of yangxinshi versus trimetazidine on exercise tolerance in patients with coronary heart disease after percutaneous coronary intervention: Multicenter, double-blind clinical trial

BackgroundOptimizing medication to improve exercise tolerance in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI) is limited. Yangxinshi tablets, an herbal-based oral medicine, relieve symptoms of angina might be that they can improve energy metabolism of the ischemic myocardium. We conducted a randomized trial to assess the efficacy and safety of Yangxinshi vs. trimetazidine in improving exercise tolerance in patients with CHD after PCI. MethodsThis prospective, randomized, double-blind, double-dummy, multicenter, non-inferiority study enrolled patients aged 18–75 years with CHD who underwent their first PCI within 2 months of diagnosis. Patients were randomized to Yangxinshi plus trimetazidine-placebo or trimetazidine plus Yangxinshi-placebo for 24 weeks. The primary endpoint was the change in metabolic equivalents (METs) assessed by cardiopulmonary exercise test (CPET) between 0 and 24 weeks. Secondary endpoints were comprehensive variables of the CPET, health status and adverse events. This study has been registered at ClinicalTrials. gov (NCT03809273). ResultsBetween August 1, 2019, and March 31, 2022, a total of 681 patients were randomized to Yangxinshi (n = 341) or trimetazidine (n = 340). After 24 weeks, the exercise tolerance of patients increased by 0.77±1.25 METs in the Yangxinshi group and 0.76±1.00 METs in the trimetazidine group (difference, 0.01; 95 % confidence interval [CI], −0.17 to 0.19), meeting the predefined non-inferiority threshold. Better outcomes were observed in the Yangxinshi group compared with the trimetazidine group for patient-reported depression (PHQ-9; −1.88±3.32 vs. −0.93±3.68; p < 0.001) and anxiety (GAD-7; −1.70±3.26 vs. −0.39±3.29; p < 0.001). Adverse events were similar in both groups. ConclusionsIn patients with CHD after PCI, Yangxinshi was non-inferior to trimetazidine in improving exercise tolerance during the 24-week treatment period. Notably, patients in the Yangxinshi group showed a better mental health profile compared with trimetazidine recipients.

The effectiveness of various intensity interval training compared to continuous training in patients with heart failure: a systematic review and network meta-analysis

Abstract Background/Introduction Cardiac rehabilitation including exercise therapy is beneficial for improving exercise tolerance, physical function, quality of life (QOL), and life expectancy in patients with heart failure. High-intensity interval training (HIIT) is increasingly reported as a new training modality to improve exercise tolerance more effectively than conventional moderate-intensity continuous aerobic training (MCT). However, the optimal intensity of HIIT for achieving the greatest effects in patients with heart failure remain controversial. Purpose This systematic review and network meta-analysis aimed to examine the effectiveness of HIIT compared to MCT on exercise tolerance in patients with heart failure. Methods We searched for studies published up to 30 January 2024 in Embase, MEDLINE via Ovid SP, PubMed, and the Cochrane Library via Wiley Online Library with no limitations on data, language, or publication status. We included randomised controlled trials comparing the efficacy of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance, aerobic threshold (AT) VO2, ventilatory equivalent of carbon dioxide (VE/VCO2) slope, and QOL. We categorized HIIT into three different intensities [&amp;gt; 80% heart rate max (HRM), 60-80% HRM, &amp;lt; 60% HRM] and compared the outcomes with those of MCT. Results We identified 15 randomised controlled trials with 557 patients from a total of 27,931 records. Our network meta-analysis revealed that the following results of peak VO2 from the comparisons among the three intensities of HIIT and MCT: &amp;gt; 80% HRM (10 studies, mean difference 1.27 ml/min/kg, 95% confidence interval -0.20 to 2.73), 60-80% HRM (3 studies, 1.47, -0.89 to 3.83), &amp;lt; 60% HRM (2 studies, 2.10, -1.22 to 5.43) (Fig. 1). Regarding AT VO2, HIIT at 60-80% HRM demonstrated significant improvements compared to MCT: &amp;gt; 80% HRM (8 studies, 0.18, -0.83 to 1.18), 60-80% HRM (2 studies, 2.50, 0.72 to 4.28), &amp;lt; 60% HRM (2 studies, 1.14, -0.93 to 3.20) (Fig. 2). Regarding VE/VCO2 slope, HIIT at 60-80% HRM also demonstrated significant improvements compared to MCT: &amp;gt; 80% HRM (7 studies, 0.29, -1.89 to 2.47), 60-80% HRM (2 studies, -3.26, -6.18 to -0.35), &amp;lt; 60% HRM (no study). The network meta-analysis did not reveal any significant differences in QOL between the various intensities of HIIT and MCT. Conclusions Our systematic review and network meta-analysis revealed that HIIT prescribed at a sub-maximal intensity, 60-80% heart rate max, is most effective in improving exercise tolerance. Higher intensity does not necessarily yield better outcomes, and future research on interval training should include detailed methodologies that account for the training intensity.Fig.1 Network meta-analysis on peak VO2Fig.2 Network meta-analysis on AT VO2

Chromatin remodeling by the histone methyltransferase SETD2 drives cardiometabolic heart failure with preserved ejection fraction

Abstract Background Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is highly prevalent and associates with a poor outcome. Pathological gene expression in heart failure is accompanied by changes in active histone marks without major alterations in DNA methylation. Histone 3 trimethylation at lysine 36 (H3k36me3) - a chromatin signature induced by the histone methyltransferase SETD2 – has shown a strong correlation with changes in gene expression in the human failing heart; however its role in cardiac disease is poorly understood. The present study investigates the role of SETD2/ H3k36me3 in cHFpEF. Purpose To investigate the role of chromatin remodelling in obese HFpEF (obHFpEF). Methods Mice with cardiomyocyte-specific deletion of SETD2 (c-SETD2-/-) were generated and subjected to high fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Cardiac function and exercise tolerance were assessed by echocardiography and Treadmill exhaustion test, respectively. ChIP-Seq datasets were employed to determine the biological pathways regulated by H3k36me3, whereas chromatin immunoprecipitation assays (ChIP) were performed to investigate SETD2/H3k36me3 enrichment on gene promoters. SETD2 gain- and loss-of-function experiments were performed in cultured cardiomyocytes (CMs) exposed to metabolic stress (palmitic acid). SETD2/H3k36me3 axis was also investigated in left ventricular (LV) myocardial specimens from patients with cHFpEF and control donors. Moreover, pharmacological inhibition of SETD2 was performed in skinned CMs from cHFpEF patients. Results Bioinformatic analysis of ChIP-Seq data in mouse CMs showed a strong involvement of SETD2/H3k36me3 in lipid-related pathways. Specifically, SETD2 and H3k36me3 were upregulated in cHFpEF vs. control mouse hearts and were highly enriched on the promoter of sterol regulatory element-binding transcription factor 1 (SREBP1) gene. SETD2 activation in cHFpEF led to SREBP1 upregulation, myocardial triglyceride accumulation and lipotoxic damage. In cHFpEF mice, cardiomyocyte-specific deletion of SETD2 prevented hypertrophic remodeling, diastolic dysfunction and lung congestion while improving exercise tolerance. Mechanistically, SETD2 deletion blunted H3K36me3 enrichment on SREBP1 promoter thus preventing SREBP1-driven lipid accumulation and leading to a significant rewiring of the cardiac lipidome. These findings were associated with restoration of autophagic flux in the cHFpEF myocardium. In CMs exposed to palmitic acid, SETD2 depletion prevented SREBP1 upregulation, whereas SETD2 overexpression recapitulated lipotoxic damage. Finally, SETD2 was upregulated in LV myocardial samples from cHFpEF patients and its pharmacological inhibition attenuated CM stiffness. Conclusions SETD2 is a new molecular target implicated in the pathophysiology of cHFpEF.

Impact of Phase III cardiac telerehabilitation on cardiorrespiratory fitness, safety and adherence in patients with ischemic heart disease

Abstract Background and Purpose Cardiac rehabilitation program (CRP) is an interdisciplinary intervention aimed to improve exercise tolerance, promote the reintegration of patients with heart disease into their normal lives, and reduce the rate of long-term complications and mortality. Of the three phases, Phase II is responsible for achieving sufficient and safe gains to guarantee adaptation, but it is in Phase III where the long-term beneficial effects and self-management will be achieved. Nevertheless, only 30% - 60% of patients report continuing regular exercise during this stage, adherence rates are heterogeneous, and the diversity of results sustained over time is wide. Therefore, cardiac telerehabilitation (CTR) emerged as an affordable tool to achieve closer and safer surveillance at Phase III. The aim of the study is to evaluate the impact of CTR on exercise tolerance, safety and phase III adherence in patients with ischemic heart disease (IHD) Methods Quasi-experimental study that follows Phase II, in which patients with IHD were assigned to virtual sessions at 1st, 3rd, 6th and 12th months, In each session, they were questioned about adherence to training, exercise tolerance, symptoms, outcomes and control of cardiovascular risk factors (CVRF). The percentage of moderate in relation to vigorous physical activity was also evaluated. After one year they underwent a cardiopulmonary exercise test to analyze comparisons in cardiorespiratory fitness (CRFit) and control of CRF between the end of Phase II and the annual follow-up of Phase III. Results At one year of Phase III follow-up, a significant gain in VO2p and maintenance of the other variables associated with fitness such as oxygen pulse (OP2) and VE/VCO2 slope were evident, with a reduction in weight and diastolic blood pressure. There was a significant gain in CRF measured by VO2p and METs-load in those patients who maintained adherence to CTR Phase III (p=0.0001, see figure), with more improvement in those with attendance&amp;gt;50% (2 or more virtual sessions; p=0.008 and p=0.004 , respectively). A directly proportional correlation was observed between the percentage of attendance and the percentage of vigorous physical activity (p&amp;lt;0.01, Pearson r=0.46, CI 0.16-0.68). A positive and significant correlation was observed between the percentage of attendance at CTR Phase III and the number of METs-load (p&amp;lt;0.05, Pearson r=0.36, CI 0.05-0.61), as well as positive and significant correlation with the amount of VO2p (p&amp;lt;0.01, Pearson r=0.50, CI 0.21-0.70) at the end of Phase III. No cardiovascular adverse events were reported. Conclusion CTR strategy in Phase III is safe, effective and has high adherence rates among patients in our population, achieving control of CVRF, maintaining levels of METs-load and obtaining even greater increases in VO2p at one year of follow-up compared to those obtained at the end of Phase II.

Opportunities to rehabilitation of multimorbid patients with asthma and obesity

BACKGROUND: The challenges of rehabilitation and achieving asthma control in patients with multimorbid conditions remain relevant despite advances in asthma treatment. Improving therapeutic approaches requires not only the development of new drugs, but also the creation of comprehensive individualized rehabilitation programs. AIM: To develop complex rehabilitation programs for patients with asthma and multimorbid diseases (obesity, osteoarthritis) and assess their impact on asthma and comorbid conditions. MATERIALS AND METHODS: 70 patients with asthma and obesity were divided into two groups: a rehabilitation group and a control group. The study evaluated external respiration functions, quality of life using Asthma Quality of Life Questionnaire (standardized), asthma control with Asthma Control Questionnaire-5 (ACQ-5), multimorbid pathology with Cumulative Illness Rating Scale (CIRS), Lequesne index, exercise capacity via 6-minute walk test, physical activity using questionnaire ODA23+, and levels of interleukin-6, interleukin-4, tumor necrosis factor alpha, leptin. RESULTS: Both groups were comparable across all assessed parameters, with most participants presenting moderate to severe asthma. Physical activity levels were low to moderate. The CIRS index was 10.0 ± 1.1 in group 1 and 9.2 ± 1.1 in group 2 (p 0.05), while the Lequesne index was 9.70 ± 1.47 and 8.80 ± 1 (p = 0.3900), respectively. After rehabilitation program, the Lequesne index in the group 1 decreased by 2.37 ± 0.60 (р 0,05), which correlated with improved exercise tolerance (6-minute walk test) and increased physical activity by 6.57 ± 2.00 (р 0.05), and increased asthma control (with ACQ-5 decreasing by 0.74 ± 0.20 points; р 0.05) and quality of life with Asthma Quality of Life Questionnaire (standardized) 3.8 ± 0.4 to 4.5 ± 0.3 (р 0.05). In group 2, no significant changes were observed in the Lequesne index, physical activity, asthma control, or quality of life (p 0.05). Proinflammatory cytokines, including interleukin-6, tumor necrosis factor alpha, and leptin, decreased significantly in group 1, while the control group showed no significant changes. CONCLUSIONS: Multicomponent rehabilitation programs tailored to the individual characteristics of patients with multimorbid conditions contribute to better management of both asthma and comorbidities. Rehabilitation improves asthma control, quality of life, and exercise tolerance. It also helps to reduce pain syndrome, increase physical activity, and decrease proinflammatory cytokines and leptin levels.

Effects of aerobic training on cardiopulmonary fitness in patients with long COVID-19: a randomized controlled trial

BackgroundLong COVID-19 is characterized by systemic deterioration of the entire body, leading to significant physical and mental disorders. Exercise training has the potential to improve persistent symptoms and cardiopulmonary functions.MethodThis was a single-center, randomized, controlled trial. Twenty-four patients aged 18 to 75 years who had a history of SARS-CoV-2 infection and long COVID symptoms. Patients were randomly allocated in a 1:1 ratio to receive either a 4-week exercise training program or an attention control group. The training group participated in 12 supervised aerobic sessions on a cycling ergometer over 4 weeks. The outcomes were to assess the impact of a 4-week aerobic exercise on the persistent symptoms and cardiopulmonary fitness, the surrogate endpoints of COVID-19 recovery and cardiopulmonary health.ResultsAfter the 4-week intervention, significant reductions were observed in the total number of symptoms in the training group. Specifically, 67.8% of patients in the training group exhibited reduced or completely resolved symptoms, in comparison to 16.7% in the control group (P = 0.013). After adjusting for gender, significant improvements in the training group were observed for exercise time (Pgroup*time = 0.028), maximum load (Pgroup*time = 0.01), and peak VO2 (Pgroup*time = 0.001), as well as O2 pulse (Pgroup*time = 0.042) and maximum heart rate (Pgroup*time = 0.007). The score of Short Form-12, depression, anxiety, perceived stress, and insomnia did not show significant changes between groups (Pgroup*time > 0.05).ConclusionA supervised aerobic training program has the potential to alleviate persistent symptoms and improve exercise tolerance in patients with long COVID-19. Further research is necessary to confirm these effects in a large population. This intervention could be easily implemented in non-hospital settings, potentially benefiting a broader range of individuals.Trial registration numberClinicalTrials.gov NCT05961462. Registered on July 25, 2023.

Lung volume reduction: surgery versus endobronchial valves.

Volume reduction is a disease-modifying treatment that aims to reshape the diseased lung towards a more normal total lung capacity by removing severely damaged and overinflated lung parenchyma. It is an effective therapeutic strategy in well-selected patients, resulting in improvements in exercise tolerance, lung function, quality of life and survival. The most widespread strategies for volume reduction are either video-assisted thoracoscopic surgery or bronchoscopic lung volume reduction. It is crucial to decide which approach would be more suitable for specific patients, as this is related to the outcome of the procedure. Factors like emphysema distribution on computed tomography, the presence or absence of collateral ventilation, the patient's pulmonary function tests, a history of other comorbidities and previous interventions might all influence the choice of procedure. It is crucial that this decision is taken by a multidisciplinary expert team to have the best outcome and fewer complications.

Design and Rationale of MYOFLAME-19 RCT: MYOcardial protection to reduce inFLAMmatory heart disease due to COVID-19 Infection using CMR Endpoints

Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute COVID-19 illness and without overt structural heart disease. Cardiac magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement prior to development of myocardial injury and impairment is missing. Prospective multicentre randomised placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodelling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no preexisting significant comorbidities or structural heart disease, undergo standardised assessments with questionnaires, CMR imaging and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical Post-COVID inflammatory involvement on baseline CMR examination are randomised to treatment with either verum or placebo for a total of 16 weeks (W16). Participants and investigators remain blinded to the group allocation throughout the study duration. The primary efficacy endpoint is the absolute change of left ventricular ejection fraction (LVEF) to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at the 5% significance level. Secondary endpoints include assessment of changes of symptoms, CMR parameters, and CPET after W16, and frequency of major adverse cardiac events after 1 year. Safety data will be analysed for frequency, severity and types of adverse events (AEs) for all treatment groups. The proportion of AEs related to the contrast agent gadobutrol will also be analysed. A calculated sample size is a total of 280 participants (accounting for 8% drop-out), randomised in 1:1 fashion to 140 in the verum and 140 placebo group. Myoflame-19 study will examine the efficacy of a myocardial protection therapy in symptomatic participants with post-COVID inflammatory cardiac involvement determined by CMR. The aim of the intervention is to reduce the symptoms and inflammatory myocardial injury, to improve exercise tolerance and preclude the development of cardiac impairment. NCT05619653.