Enhance Exercise Capacity Research Articles

Effectiveness of rate-adaptive pacing on patients with chronotropic incompetence: Systematic review and meta-analysis of randomized controlled trials.

Rate-adaptive pacing (RAP) complements heart rate (HR) responses in patients with cardiac pacing devices and chronotropic incompetence, although improvements in exercise capacity have varied across reported studies. The purpose of this study was to evaluate the effectiveness of the RAP mode across different clinical settings. A systematic review and meta-analysis were conducted according to PRISMA guidelines. MEDLINE and EMBASE databases were searched through May 2024. Randomized controlled trials comparing RAP-on with RAP-off modes in patients with chronotropic incompetence were included. Outcomes related to exercise capacity, such as peak oxygen uptake (VO2), exercise duration, and patient-reported outcomes (PROs), were analyzed. Twelve trials with a total of 1199 patients were included. The meta-analysis showed that RAP-on significantly improved peak VO2 (mean difference [MD]: 1.35 ml/kg/min, 95 % confidence interval [CI]: 0.47 to 2.23) and exercise duration (MD:0.74 min, 95 % CI: 0.14 to 1.33) with augmenting peak HR (MD: 19 bpm, 95 % CI: 13 to 26) during cardiopulmonary exercise tests. The effectiveness of RAP on exercise capacity blunted particularly in patients with heart failure (HF) (MD: 0.36 ml/kg/min, 95 % CI: -0.88 to 1.60) compared with those without HF (MD: 1.95 ml/kg/min, 95 % CI: 0.66 to 3.23). PROs showed no significant improvement with RAP-on except for one study including non-HF. RAP-on mode significantly enhances exercise capacity in patients with chronotropic incompetence, however, the benefits are less pronounced in patients with concomitant HF. In patient with HF, careful assessment is crucial to identify potential need for advanced therapeutic approach following the RAP-on pacing.

Effect of ticagrelor combined with metoprolol extended-release tablets on cardiac function and clinical prognosis in elderly patients with acute coronary syndrome after percutaneous coronary intervention

BackgroundAcute coronary syndrome (ACS) poses significant risks to older individuals. This study sought to assess the impact of combining ticagrelor and metoprolol extended-release tablets on clinical prognosis and cardiac function in elderly ACS patients following percutaneous coronary intervention (PCI).MethodsFrom February 2022 to February 2023, 90 elderly ACS patients who underwent PCI at our institution were retrospectively enrolled and divided into two groups: an observation group (OG) and a control group (CG), with 45 patients in each group. The CG received oral metoprolol extended-release tablets, while the OG received both oral metoprolol extended-release tablets and ticagrelor. Prognostic indicators and cardiac function were evaluated before and after treatment.ResultsThe treatment effectiveness rate in the OG was 97.78%, significantly higher than the CG's rate of 77.78% (P < 0.05). Post-treatment, the OG displayed notable improvements in cardiac function, including significantly higher left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), and cardiac index (CI) compared to the CG (P < 0.05). Both groups experienced enhanced exercise capacity, as evidenced by longer exercise duration (ED) and improved 6-min walking test (6MWT) results, with the OG showing superior gains (P < 0.05). Additionally, the OG had significantly higher serum levels of cardiac troponin T (cTnT) and creatine kinase isoenzyme (CK-MB) than the CG (P < 0.05). Decreases in serum levels of sICAM-1, MMP-9, and hs-CRP were observed in both groups, with more pronounced improvements in the OG (P < 0.05). The incidence of adverse prognostic events in the OG was significantly lower at 8.89%, compared to 37.78% in the CG (P < 0.05).ConclusionTicagrelor combined with metoprolol extended-release tablets can significantly improve cardiac function, motor performance, and quality of life in ACS patients after PCI. Additionally, it effectively increases myocardial injury markers and reduces serum inflammatory factor levels.

Effect of different cold acclimation methods on the exercise capacity of mice in low-temperature environments.

This study aimed to evaluate the effects of different cold acclimation strategies on exercise performance in male mice exposed to low-temperature environments. Male mice were subjected to five distinct acclimation regimens over 8 weeks: immersion at 10°C (10 °CI) or 20°C (20 °CI), swimming at 10°C (10 °CS), 20°C (20 °CS), or 34°C (34 °CS). During the first 2 weeks, the acclimation time progressively decreased from 30min to 3min per day, and the water temperatures were lowered from 34°C to the target levels, followed by 6 weeks of consistent exposure. Body weight, food intake, and rectal temperature were monitored throughout the study. Post-acclimation assessments included low-temperature exhaustion exercise ability testing; 16S rDNA sequencing of gut microbiota; and quantification of gene expression related to brown adipose thermogenesis, skeletal muscle synthesis, and degradation. (1) After 8 weeks of acclimation, neither serum adrenaline nor angiotensin II levels significantly increased in mice exposed to 10°C or 20°C water. (2) Cold acclimation extended the endurance time under low-temperature conditions, notably in the 20 °CI, 10 °CS, and 20°CS groups. (3) Compared with the control (C) group, the 20 °CI and 10°CS groups showed significantly increased UCP1, IGF-1, AKT, and mTOR gene expression levels (P<0.05). The expression levels of MAFbx and MuRF1 genes in the 10°CS and 20°CS groups significantly decreased compared with those in the C group (P<0.05). (4) Compared with the C group, the 20 °CI, 10 °CS, and 20°CS groups demonstrated significant changes in intestinal microbiota diversity. Specifically, the abundance of Akkermansia strains significantly increased in the 20 °CI and 10°CS groups. The abundance of Ruminococcus and Prevotellaceae_UCG-001 significantly increased in the 20°CS group. Exercise in cold environments can activate genes related to heat production and skeletal muscle synthesis and increase the abundance of beneficial bacteria producing short-chain fatty acids, thereby modulating host metabolism, accelerating the formation of cold acclimation, and enhancing exercise capacity in low-temperature environments.

Efficacy and Safety of Sotatercept in Pulmonary Arterial Hypertension: A Systematic Review

Context: Pulmonary arterial hypertension (PAH) is characterized by the narrowing and remodeling of small pulmonary arteries, resulting from an imbalance in signaling pathways that regulate cell proliferation. Current therapeutic strategies for PAH target specific pathways to enhance pulmonary hemodynamics, including soluble guanylate cyclase stimulators, endothelin receptor antagonists, and prostacyclin pathway modulators. Sotatercept emerges as a promising therapeutic option that targets the underlying mechanism of PAH by improving the integrity of the endothelial layer of pulmonary arteries, promoting cellular proliferation, and alleviating vascular dysfunction. Objectives: This study systematically aims to review existing literature on the efficacy and safety of sotatercept in treating PAH. Methods: A comprehensive search was conducted across five online databases (PubMed, Scopus, Web of Science, Embase, and Google Scholar) to identify relevant studies. Original studies with human participants that investigated the efficacy and safety of sotatercept in patients with PAH were included. The primary outcomes assessed included clinical parameters such as pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), mean right atrial pressure (mRAP), mean pulmonary artery pressure (mPAP), 6-minute walk distance (6MWD), and improvements in World Health Organization functional class (WHO FC) over follow-up periods of up to 24 weeks. Additionally, adverse events such as thrombocytopenia, bleeding, headaches, telangiectasia, increased blood pressure, nausea, diarrhea, fatigue, and epistaxis were evaluated. Results: After screening, nine studies involving a total of 323 participants were included in the review. The analysis revealed that sotatercept significantly reduced PVR and led to notable improvements in 6MWD and NT-proBNP levels among patients. The treatment was well-tolerated across various dosages, with all evaluated adverse events being manageable. Conclusions: The findings indicate that sotatercept is an effective therapeutic intervention for patients with PAH, significantly reducing PVR while enhancing exercise capacity and improving biomarkers of heart failure. The adverse effects associated with sotatercept were generally mild and manageable. The results support the potential of sotatercept as a valuable addition to the current treatment landscape for PAH. Further studies are warranted to comprehensively evaluate all related outcomes and potential adverse events associated with this therapy.

Abstract 4131445: The Effects of Percutaneous Pulmonary Valve Implantation (PPVI) or Stenting on RV Diastolic Relaxation

Introductions: Pulmonary regurgitation is a diastolic phenomenon but little is known of the impact of RV-PA conduit interventions on RV diastolic function. We measured the acute effects of PPVI or stent implantation on RV diastolic relaxation with high-fidelity pressure catheters. Methods: Right and left heart pressure measurements with Millar Mikro-Cath pressure catheters in children undergoing RV-PA conduit intervention, who had also had an MRI. The relaxation time constant (RV-tau) was calculated as the time constant of the monoexponential pressure decay in the interval between the pressure at dP/dt min (P 0 ) to when the pressure fell to 10% of P 0 . Result: The age for PPVI (n=29) or stent (n=21) implantations were (mean ± sd): 14 ± 2.8 and 11.8 ± 4.2 years, respectively. RV-tau decreased 33% in the PPVI group and increased 11% in the Stent group (Table 1). The absolute value of RV dP/dt min decreased 9% in the Stent but not the PPVI group. The absolute value of LV dP/dt min increased 12% in the PPVI but not the Stent group. There was a small increase in peak VO 2 at the last follow-up (median 1.04 years, range 0.15-4.69 years) in the PPVI but not the Stent group compared to baseline (from 27.1 to 31.6 ml/kg/min, p = 0.01). The Δpeak VO 2 correlated with ΔRV-tau (r = 0.75, p = 0.01, n = 10) but not with ΔRV-PA gradient or pre pulmonary regurgitation fraction. Conclusions: PPVI results in faster RV diastolic relaxation. This may contribute to post-procedure enhanced exercise capacity more than either RV pressure and volume unloading alone.

Lack of sex-specific differences in the associations between the dimensions of great vessels and exercise performance in amateur cyclists.

Endurance training enhances exercise capacity and triggers cardiovascular adaptations in both males and females. We investigated the relationship between the dimensions of great vessels and exercise capacity in amateur cyclists while considering sex differences. Using resting transthoracic echocardiography, we measured the dimensions of the main pulmonary artery (PA), aorta, and inferior vena cava (IVC) in 190 participants, who subsequently underwent a cardiopulmonary exercise test (CPET) until exhaustion. The mean age of study participants was 30 years. Males (71%) exhibited a larger aortic annulus (approximately 3.5 mm, p<0.0001) and PA diameter (2.4 mm, p<0.0001) than females. No significant sex differences were found in expiratory or inspiratory IVC diameters. Males achieved greater peak exercise capacity, including workload, O2 consumption (VO2), and O2 pulse. Aortic and PA dimensions showed strong correlations with energy expenditure, workload, VO2, and O2 pulse. However, these correlations weakened when analyzed separately by sex. Multivariate linear regression revealed associations between CPET results, vessels size, and sex, with sex differences observed only in the intercepts-not in interactions between sex and vessels size. Despite males having better CPET results and larger vessels, the relationships between peak exercise capacity parameters and vessel dimensions were similar in both sexes. Larger vessel dimensions (of the aorta, PA, and IVC) were associated with greater peak exercise capacity in amateur cyclists, with no significant sex differences in these associations.

Ginsenoside-Re-rich ethanol extract of Panax ginseng berry enhances healthspan extension via mitostasis and NAD metabolism

BackgroundGinseng Berry Concentrate (GBC) enhances exercise capacity in mice, but the effects of its key component, ginsenoside Re (G-Re), on aging and mitochondrial function are not well understood. This study investigates the impact of G-Re on mitophagy and its potential to promote healthy aging. MethodsExperiments in C2C12 myocytes and HeLa-mitoKeima-PARKIN cells assessed GBC and G-Re's effects on mitophagy, supported by Gene Set Enrichment Analysis. G-Re was identified as the primary component of GBC via high-performance liquid chromatography. The influence of G-Re on lifespan and healthspan was examined in Caenorhabditis elegans, with a focus on mitophagy pathways. ResultsGBC and G-Re significantly induced mitophagy and enhanced mitochondrial gene expression, improving mitochondrial function. G-Re extended lifespan and healthspan in C. elegans, effects absent in mitophagy-impaired mutants. ConclusionG-Re enhances mitochondrial function and promotes healthy aging through mitophagy, suggesting its potential for mitigating age-related functional declines.

Effectiveness and safety of exercise training and rehabilitation in elderly patients after heart valve intervention: A systematic review and meta-analysis of randomized controlled trials

ObjectiveTo investigate the effectiveness and safety of exercise rehabilitation in older adults undergoing intervention for heart valve disease. MethodPubMed, Embase, Cochrane Library, CINAHL, Ovid Medline, SPORTDiscus, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang were systematically searched until January 2024. Risk-of-bias assessments were performed using the Cochrane risk-of-bias tool. A meta-analysis of the following indexes was performed using RevMan 5.4 software. ResultsNine trials involving 631 patients were ultimately included. Exercise rehabilitation significantly reduced the risk of adverse events, increased the 6-minute walk distance, improved the physical component of quality of life, and shortened the length of postoperative hospitalization. However, exercise rehabilitation did not affect all-cause mortality, left heart ejection fraction, or peak oxygen uptake. ConclusionsExercise rehabilitation may enhance exercise capacity, reduce the incidence of adverse events, and shorten the length of postoperative hospitalization in older adults undergoing intervention for heart valve disease.

The safety and efficacy of treprostinil for the treatment of pulmonary arterial hypertension: a systematic review and meta-analysis of randomized controlled trials

Abstract Introduction Pulmonary arterial hypertension (PAH) is a severe and life-threatening condition characterized by increased pulmonary vascular resistance and elevated mean pulmonary artery pressure. Treprostinil, a prostacyclin analog, has vasodilatory and anti-remodeling effects on pulmonary arterial smooth muscle cells, indicating promising benefits in enhancing exercise capacity, improving hemodynamics, and reducing morbidity in patients with PAH. Aim The primary objective of this systematic review and Meta-analysis is to assess the efficacy and safety of Treprostinil in patients with PAH. Methods We systematically searched PubMed, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov from inception until July 2023. Randomized controlled trials comparing Treprostinil with Placebo were selected. We used the mean values to compare continuous data and odds ratio (OR) for dichotomous outcomes with their 95% confidence interval (CI). Results We included 7 studies with a total of 2,447 patients. The Treprostinil group was favored over the control group in terms of 6-minute walk distance (6MWD) (Mean difference (MD), meters (m)) (MD = 15.16 m, 95% confidence interval (CI) (10.42 – 19.90 )). Subgroup analysis based on the route of administration revealed a 6MWD of (MD = 13.55 m (95% CI (7.82 – 19.28)) for oral administration and (MD = 17.49 m, 95% CI (6.01 – 28.89)) for intravenous (IV)/subcutaneous (SC) administration, indicating enhanced exercise capacity. When evaluating the efficacy of Treprostinil for oral administration, there was a slight but non-significant trend toward functional improvement (Odds Ratio (OR): 1.36; 95% CI: 0.95 to 1.93) and no significant change in maintaining functional status (OR: 0.94; 95% CI: 0.59 to 1.51). In terms of functional deterioration, the risk was also not significantly reduced (OR: 0.84; 95% CI: 0.36 to 1.98). Safety assessment of the drug was based on clinical, mortality, and adverse events outcomes. Clinically, Treprostinil demonstrated a protective effect against disease progression, evidenced by a reduced risk of clinical worsening (OR: 0.69; 95% CI: 0.52 to 0.91). Mortality rates were not significantly impacted by Treprostinil addition (OR: 0.95; 95% CI: 0.57 to 1.58 for oral, 0.80; 95% CI: 0.32 to 1.98 for IV/SC). However, the incidence of adverse events was notably higher among Treprostinil-treated patients, particularly with oral administration. Conclusion The addition of Treprostinil therapy for patients with PAH significantly improved exercise capacity, as evidenced by an increase in the 6MWD compared to control groups and demonstrated a reduced risk of clinical worsening. The incidence of adverse events was higher among Treprostinil-treated patients, especially with oral administration, potentially impacting quality of life.Forest plot of the 6MWD

Comparative effects of ranolazine and trimetazidine on cardiac structure and exercise capacity in a healthy rat model: a new doping agent?

Abstract Background/Introduction Anti-anginal drugs that have been shown to improve myocardial energy use include ranolazine and trimetazidine [1]. An inquiry is warranted into their ability to impact cardiac functions and exercise capacity. Purpose This study aims to evaluate the effects of ranolazine; and trimetazidine as a positive control group on cardiac structure and exercise capacity in a rodent model in comparison with the control group. Methods In a randomized, controlled trial, 24 Sprague-Dawley rats were divided into three groups: control, ranolazine, and trimetazidine. Rats were given daily doses of ranolazine (50 mg/kg/1 ml) [2], trimetazidine (10 mg/kg/1 ml) [3], or saline (control) via gastric gavage for 30 days. At the beginning of the trial, as well as on the 15th and 30th days, the rats were weighed, placed on rotarod, and assessed using transthoracic echocardiography (Figure 1). The rats underwent 21 days of forced swimming testing. According to the guidelines for rat exercise testing [4], signs of exhaustion, lack of coordinated movements, and failure to surface for three seconds following submersion in the water were designated as grounds for terminating the test. Weight, rotarod durations, M-mode and Doppler measurements, and forced swimming test durations were recorded on the 0th, 15th, and 30th days. Results No discernible differences were found between the groups in the initial evaluations. By using echocardiography, the left ventricular masses expanded in all three, indicating the emergence of an athlete's heart. In comparison to the control group, the ranolazine and trimetazidine groups showed considerable increases in their ability to exercise. In particular, the swimming times of the trimetazidine group and the ranolazine group improved to a mean of 1889 seconds by the 21st session, 1700 seconds in the trimetazidine group, and 1548 seconds in the control group (Figure 2), respectively, indicating enhanced cardiac performance. Conclusion(s) Ranolazine exhibits significant potential to enhance exercise capacity and cardiac efficiency in rats, surpassing the effects observed with trimetazidine. Trimetazidine is already registered as a doping agent in WADA [5]. These findings highlight the potential use of ranolazine as a performance enhancing agent in healthy subjects for a malicious purpose of creating unfair advantages in professional sports. Further studies in human subjects are needed.Figure 1Figure 2

Whole milk protein powder separated by low-temperature nanofiltration membrane administration alleviates sepsis-induced myopathy

Sepsis-induced myopathy (SIM) has been recognized as a critical risk factor for the development of acquired muscle weakness among patients in the intensive care unit. These individuals frequently encounter inadequate dietary intake and malnutrition. With the aggravation of the severity of the person’s condition, leading to increased skeletal muscle protein breakdown and reduced synthesis, which is an urgent problem to be solved in clinical nutritional treatment. Whole milk protein powder (WMPP) has promising bioactive nutrients and holds promising potential for enhancing skeletal muscle mass. The study was designed to delve into the potential effects and mechanisms of WMPP intervention for increaseing skeletal muscle mass on SIM mice. Our results clearly show that the intervention with WMPP can significantly improve the exercise capacity and skeletal muscle mass in SIM mice. It significantly increases the diameter and cross-sectional area (CSA) of skeletal muscle fibers, while effectively reducing the excessive aggregation of collagen fibers and the abnormal accumulation of adipose tissue in the skeletal muscle of SIM mice. Moreover, WMPP intervention also significantly alleviated the oxidative stress status of mitochondria, which subsequently enhanced the expression of mitochondrial metabolic enzymes. The mechanism may be associated with decreased AMPK phosphorylation in skeletal muscle tissue and simultaneously increased phosphorylation of mTOR, p70S6K1, and 4EBP-1 in SIM mice. In summary, the WMPP intervention significantly enhances exercise capacity and skeletal muscle mass while mitigating the oxidative stress status of mitochondria. Furthermore, it regulates skeletal muscle anabolism via the AMPK/mTOR signaling pathway in SIM mice.

Individualized and Controlled Exercise Training Improves Fatigue and Exercise Capacity in Patients with Long-COVID.

(1) Background: Long-term health effects after SARS-CoV-2 infections can manifest in a plethora of symptoms, significantly impacting the quality of life of affected individuals. (2) Aim: The present paper aimed to assess the effects of an individualized and controlled exercise intervention on fatigue and exercise capacity among Long-COVID (LC) patients in an ambulatory setting. (3) Methods: Forty-one (n = 41) LC patients performed an exercise protocol with an individualized control of the patients' training intensity during the study period based on the individual's ability to achieve the target criteria. The program was carried out two to three times a week, each session lasted 30 min, and the study parameters were recorded at the beginning of the program, as well as after 6 and 12 weeks, respectively. These included both patient-reported (PCFS questionnaire, FACIT-Fatigue questionnaire) and objective (one-minute sit-to-stand test (1MSTST), workload) outcomes. (4) Results: The exercise training intervention resulted in significant improvements in the FACIT-Fatigue (F(2, 80) = 18.08, p < 0.001), 1MSTST (χ2(2) = 19.35, p < 0.001) and workload scores (χ2(2) = 62.27, p < 0.001), while the PCFS scores remained unchanged. Changes in the workload scores were dependent on the frequency of the completed exercise sessions and were higher in the LC patients with a moderate Post COVID Syndrome Score (PCS) compared to a severe PCS. (5) Conclusions: The individualized and controlled training approach demonstrated efficacy in reducing fatigue and enhancing exercise capacity among outpatient LC patients. However, for complete regeneration, a longer, possibly indefinite, treatment is required, which in practice would be feasible within the framework of legislation.

Normobaric hypoxia accelerates high-intensity intermittent training-induced mitochondrial biogenesis (PGC-1α)- and dynamics (OPA1)-related protein expressions in rat gastrocnemius muscle.

High-intensity intermittent training (HIIT) in a normobaric hypoxic environment enhances exercise capacity, possibly by increasing the mitochondrial content in skeletal muscle; however, the molecular mechanisms underlying these adaptations are not well understood. Therefore, we investigated whether HIIT under normobaric hypoxia can enhance the expression of proteins involved in mitochondrial biogenesis and dynamics in rat gastrocnemius muscle. Five-week-old male Wistar rats (n = 24) were randomly assigned to the following four groups: (1) sedentary under normoxia (20.9% O2) (NS), (2) training under normoxia (NT), (3) sedentary under normobaric hypoxia (14.5% O2) (HS), and (4) training under normobaric hypoxia (HT). The training groups in both conditions were engaged in HIIT on a treadmill five to six days per week for nine weeks. From the fourth week of the training period, the group assigned to hypoxic conditions was exposed to normobaric hypoxia. Forty-eight hours after completing the final training session, gastrocnemius muscles were surgically removed, and mitochondrial enzyme activity and mitochondrial biogenesis and dynamics regulatory protein levels were determined. Citrate synthase (CS) activity and mitochondrial oxygen phosphorylation (OXPHOS) subunits in the gastrocnemius muscle in the HT significantly exceeded those in the other three groups. Moreover, the levels of a master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and a mitochondrial fusion-related protein, optic atrophy 1 (OPA1), were significantly increased by HIIT under normobaric hypoxia. Our data indicates that HIIT and normobaric hypoxia increase the expression of mitochondrial biogenesis- and dynamics-related proteins in skeletal muscles.

Nebulized fentanyl does not improve exercise capacity or dyspnoea in fibrosing interstitial lung disease.

Exercise intolerance and exertional dyspnoea are hallmarks of fibrosing interstitial lung disease (FILD) and are associated with worse prognosis and quality of life. Activation of pulmonary vagal afferents influences the ventilatory pattern and contributes to the sensation of dyspnoea. We tested the hypothesis that nebulized fentanyl, which might attenuate aberrant pulmonary afferent activity in FILD, reduces ventilation and dyspnoea while extending exercise endurance time (EET). In this randomized, single-blind, placebo-controlled study, eight FILD patients (two males, 71±6years of age) performed incremental cardiopulmonary cycle exercise tests following nebulization of either fentanyl citrate (100 µg) or 0.9% saline. Previous work indicated that this dose was unlikely to produce central effects. Comparisons between treatment conditions at rest were undertaken using Student's paired t-test, and exercise data were evaluated with two-way ANOVA with repeated measures. Dyspnoea was assessed using the Borg dyspnoea scale. Resting respiratory variables were not different following treatment with fentanyl and saline; however, resting heart rate was lower following fentanyl (P=0.002) and remained lower throughout exercise compared with placebo (P=0.008). Fentanyl did not increase EET (placebo 334±117s vs. fentanyl 348±126s, P=0.250) although overall minute ventilation was reduced slightly (mean difference: -0.97 L/min, P=0.022). There were no differences in ratings of dyspnoea intensity or unpleasantness between the conditions either at rest or at end-exercise. Nebulized fentanyl did not improve EET or exercise dyspnoea but did decrease minute ventilation during exercise, although the extent of this reduction appears clinically insignificant. These findings suggest that nebulized fentanyl is unlikely to offer significant benefits for enhancing exercise capacity in FILD.

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

BackgroundAficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined. ObjectivesThis responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten. MethodsPatients who were symptomatic of oHCM were randomized to aficamten (n = 142) or placebo (n = 140) daily for 24 weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient <30 mm Hg and <50 mm Hg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or ≥10-point change in Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score), enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake), and ≥50% reduction in N-terminal pro–B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated. ResultsAt 24 weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease ≥50% in N-terminal pro–B-type natriuretic peptide (84% vs 8%) (P ≤ 0.002 for all). An improvement in ≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24 weeks compared with 15 (52%) from the placebo group (P = 0.002). ConclusionsTreatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818)

Effectiveness of Home-Based Cardiac Rehabilitation with Optimized Exercise Prescriptions Using a Mobile Healthcare App in Patients with Acute Myocardial Infarction: A Randomized Controlled Trial.

Despite the effectiveness of cardiac rehabilitation (CR), the actual participation rate in CR is low. While home-based CR offers a viable alternative, it faces challenges in participation due to factors such as a lack of self-motivation and fear of exercising without supervision. Utilizing a mobile healthcare application (app) during counseling may be an effective strategy for patients. Therefore, the aim of this study was to assess whether 6 weeks of home-based CR with exercise readjustment using a mobile app is an effective therapy for patients with acute myocardial infarction (AMI). Post-AMI patients eligible for home-based CR were randomized into the intervention group (CR-Mobile) and the control group, which followed the usual home-based CR protocol (CR-Usual). Both groups participated in a 6-week home-based CR program, with exercise readjustment and encouragement carried out every 2 weeks. The CR-Mobile group was supervised using data recorded in the mobile app, while the CR-Usual group was supervised via phone consultations. The primary outcome measured was maximal oxygen consumption (VO2max). Within-group comparisons showed significant improvements in VO2max (PCR-Mobile = 0.011 vs. PCR-Usual = 0.020) and METs (PCR-Mobile = 0.011 vs. PCR-Usual = 0.011) for both groups. These findings suggest that a 6-week home-based CR program with exercise readjustment using a mobile app can potentially enhance exercise capacity as effectively as verbal supervision.

Impact of pulmonary rehabilitation on exercise capacity, health-related quality of life, and cardiopulmonary function in lung surgery patients: a retrospective propensity score-matched analysis.

Pulmonary rehabilitation is considered beneficial for patients undergoing lung surgery, yet its specific impacts on exercise capacity, health-related quality of life (HRQL), and cardiopulmonary function require further elucidation. This study aimed to evaluate the effect of PR on these outcomes in patients undergoing lung surgery using a retrospective propensity score-matched analysis. We retrospectively analyzed 420 patients with non-small cell lung cancer (NSCLC) who underwent lung surgery from January 2022 to May 2024. Among these, 84 patients received PR while 336 did not (control group). Propensity score matching (PSM) at a 1:1 ratio yielded 46 patients in each group. Baseline characteristics, spirometry, cardiopulmonary exercise testing, respiratory muscle strength, HRQL, and muscle measurements were assessed pre-and post-surgery. Before PSM, significant differences existed between groups, with the PR group being older and having different pulmonary function baselines. After PSM, groups were well-balanced. Postoperatively, the PR group showed significant improvements in FEV1/FVC (64.17% vs. 50.87%, p < 0.001), FEV1 (2.31 L/min vs. 1.75 L/min, p < 0.001), and predicted FVC percentage (88.75% vs. 68.30%, p < 0.001). Cardiovascular responses showed a lower CI during exercise in the PR group post-PSM (6.24 L/min/m2 vs. 7.87 L/min/m2, p < 0.001). In terms of exercise capacity, the PR group had higher maximal WR percentage (104.76% vs. 90.00%, p = 0.017) and peak VO2 (1150.70 mL/min vs. 1004.74 mL/min, p = 0.009). PR also resulted in less leg soreness and lower total CAT scores postoperatively. Muscle measurements indicated significantly smaller reductions in ΔHUESMCSA and percentage change in the PR group. Pulmonary rehabilitation significantly enhances exercise capacity, HRQL, and cardiopulmonary function in patients undergoing lung surgery. It also mitigates postoperative muscle loss, underscoring its importance in the postoperative management of lung surgery patients.

Effect of Pre- and Post-Dialysis Exercise on Functional Capacity Using Portable Ergometer in Chronic Kidney Disease Patients.

To assess whether performing exercises during hemodialysis reduces the risk of developing intradialytic hypotension and enhances exercise capacity in patients with chronic kidney disease. This study included patients aged ≥18 years undergoing hemodialysis. Participants performed exercises using a portable lower extremity ergometer during hemodialysis sessions for 3 weeks. Data regarding walking distance, knee strength, quality of life, fat-free mass, arterial pressure, blood pressure, heart rate, frequency of intradialytic hypotension, fatigue, and duration of hemodialysis were collected and analyzed. Significant improvements in walking distance and knee strength were observed following the implementation of exercise training during hemodialysis. Although there was no significant reduction in the frequency of intradialytic hypotension, a decreasing trend was noted. Other parameters such as quality of life and fatigue did not show significant changes. Using a portable ergometer during hemodialysis improved exercise capacity and knee strength in patients with chronic kidney disease. There was a trend toward reduced intradialytic hypotension, suggesting potential cardiovascular benefits. Further research with larger sample sizes is needed to confirm these findings.

Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function.

Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.

The effect of a hybrid structured pulmonary rehabilitation education program for patients with lung cancer with a high risk of postoperative pulmonary complications: A quasi-experimental study

PurposeThe absence of standardized protocols and education are the main obstacles to perioperative pulmonary rehabilitation (PR), especially for patients with high-risk factors of postoperative pulmonary complications (PPCs). We aimed to explore the effect of a hybrid structured pulmonary rehabilitation education program (SPREP) on patients with lung cancer at high risk of PPCs. MethodsA quasi-experimental trial with a pre-post test design was conducted. The control group (n = 53) adopted routine perioperative pulmonary rehabilitation, while the intervention group (n = 53) received SPREP. Respiratory function, 6-min walk distance, Borg dyspnea scale, quality of life, anxiety–depression scores at admission, discharge, 2 weeks and 3 months post-discharge, and incidence of PPCs were compared between the two groups. ResultsThere were no significant differences on the 6-min walk distance and Borg Dyspnoea Scale at discharge between the two groups (P > 0.05), whereas the intervention group showed improved performance at the remaining time points (P < 0.05). In addition, the intervention group had improved exercise capacity, pulmonary function and quality of life, reduced levels of anxiety and depression at discharge, 2 weeks post-discharge and 3 months post-discharge (P < 0.05). In addition, incidence of PPCs was significantly reduced in the intervention group, especially postoperative pneumonia. ConclusionsThe SPREP could show significant benefits in enhancing exercise capacity, lung function, and quality of life, while diminishing the occurrence of PPCs and mitigating the levels of anxiety and depression, future large RCT need to further explore the efficacy. Trial registrationThis study was registered with the China Clinical Trial Registration Center (ChiCTR) under the Clinical Trial Registration Number [ChiCTR2200066698].