Increase In Peak Oxygen Consumption Research Articles

Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.

Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

The effect of cardiac rehabilitation on cardiopulmonary function after coronary artery bypass grafting: A systematic review and meta-analysis

We carried out a meta-analysis on the effect of cardiac rehabilitation (CR) on cardiopulmonary function after coronary artery bypass grafting (CABG). Four databases were searched for studies comparing CR with control. A random-effects model was used to pool mean difference (MD). The meta-analysis showed an increase in peak oxygen consumption (peak VO2) (MD= 1.93mL/kg/min, p= 0.0006), and 6-min walk distance (6MWD) (MD= 59.21 m, p<0.00001), and a decrease in resting heart rate (resting HR) (MD= 5.68bpm, p<0.0001) in the CR group. The subgroup analysis revealed aerobic exercise could further improve resting HR and peak HR, and physical/combination with aerobic exercise could further increase 6MWD. The improvement of peak VO2, workload, resting HR, peak HR, and 6MWD regarding CR performed within one week after CABG is greater than that one week after CABG. CR after CABG can improve the cardiopulmonary function, which is reflected by the improvement of peak VO2, 6MWD, and resting HR.

Efficacy and Safety of Mavacamten in the Treatment of Hypertrophic Cardiomyopathy: A Systematic Review.

Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We aim to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive HCM. This systematic review of the literature followed the PRISMA guidelines. Title/abstract and topics were searched using the following term: "mavacamten". The electronic research literature databases included the Cochrane Library, MedLine, and clinicaltrials.gov from July to August 2022. Primary efficacy endpoint was to assess clinical response at the end of treatment compared with baseline, defined as, at least one New York Heart Association (NYHA) class reduction. Two secondary endpoints from baseline were determined. The first was defined as improvement in mixed venous oxygen pressure (pVO2). The second was defined as reduction of the post-exercise left ventricular outflow tract (LVOT) gradient. We included in our analyses data from four studies that met our review eligibility criteria. There were three randomised placebo-controlled clinical trials and one non-randomised open-label clinical trial. All four studies showed a reduction in NYHA class from mavacamten use. Three out of four studies demonstrated >1 NYHA functional class improvement ranging from 34% to 80%, while only one study showed a smaller percentage of patients remaining at class 3. Three out of four studies measured pVO2 as an outcome, and all three studies noticed an increase in peak oxygen consumption after mavacamten treatment. Additionally, three out of four studies measured post-exercise LVOT gradient reduction as an outcome and all three found significant reduction in the post-exercise LVOT gradient after treatment. The most commonly observed adverse side effects were atrial fibrillation and decreased left ventricular ejection fraction, but all participants recovered without long-term sequelae and only one patient dropped out of the trial. Mavacamten has a greater efficacy than placebo in the treatment of HCM. It also showed promising tolerability and efficacy profiles in the treatment of HCM in adults. The three endpoints used in the evaluation of studies were reduction in NYHA class, increase in pVO2, and post-exercise LVOT gradient reduction. Mavacamten showed greater reduction in NYHA, larger effects on increase of pVO2, and significant reduction of the LVOT gradient. Mavacamten was also found to be well tolerated, like the placebo. The side effect profile was limited for the majority of individuals taking mavacamten. In the future, authors recommended dose-optimisation studies, and studies that evaluate mavacamten both in comparison to, and in conjunction with other current treatments.

Right Ventricular Morphology and Function after Exercise Training in People with Systemic Sclerosis: A Randomized Controlled Pilot Study

Vascular dysfunction and its concomitant multi-organ involvement, including cardiac involvement, affects prognosis in systemic sclerosis (SSc) patients. Regular exercise has demonstrated to be able to improve vascular function in SSc. However, the effects of an exercise program on the heart and specifically in right ventricular (RV) morphology and function in SSc have yet to be explored. The study aimed to examine whether a 3-month combined exercise program can affect RV morphology and function in SSc patients. Twenty-eight SSc patients were randomly allocated to either the exercise training (ET) or the control (CON) group. Baseline and follow-up assessments consisted of a cardiopulmonary exercise test along with both a conventional and a two-dimensional speckle tracking echocardiography (2DSTE) focused on RV morphology and function. Following the baseline assessments, Group ET participated in a supervised combined exercise program for 12 weeks, while group CON received their usual care. The ET group demonstrated increases in peak oxygen consumption by 25.1% (p < 0.001), global RV free wall longitudinal systolic strain by 6.69% (p < 0.03), RV free wall longitudinal systolic strain of the basal segment by 13.5% (p < 0.001), and global RV four-chamber longitudinal systolic strain by 6.76% (p < 0.03) following the exercise program. No differences were observed in group CON. Combined exercise improved cardiorespiratory efficiency and indices of RV systolic function, as assessed by the 2DSTE, in SSc patients.

Combined effect of physical exercise and hormone replacement therapy on cardiovascular and metabolic health in postmenopausal women: A systematic review and meta-analysis.

The cardioprotective effect of postmenopausal hormone replacement therapy (HRT) has been demonstrated in several studies. Similarly, physical exercise has yielded positive results. However, the effects of their combination remain inconclusive. This review describes the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We searched the Scopus, Web of Science, PubMed, and Embase databases and included randomized controlled trials published up to December 2021 on the combined effects of physical exercise and hormone therapy on cardiovascular and metabolic health in postmenopausal women. We identified 148 articles, of which only seven met the inclusion criteria (386 participants; 91 [23%] HRT + exercise; 104 [27%] HRT; 103 [27%] exercise; 88 [23%] placebo). The combined treatment further decreased systolic blood pressure (SBP) compared to the isolated effect of aerobic training (AT) (mean difference [MD]=-1.69; 95% confidence interval [CI]=-2.65 to -0.72, n=73). Nevertheless, it attenuated the decrease in diastolic blood pressure (DBP) (MD=0.78; 95%CI: 0.22-1.35, n=73), and the increase in peak oxygen consumption (VO2 peak) promoted by exercise (AT + HRT=2.8±1.4 vs AT + placebo=5.8±3.4, P=0.02). The combination of AT and oral HRT improved SBP. However, AT alone seemed to have a better effect on physical fitness and DBP in postmenopausal women.

Mavacamten induces a clinical, hemodynamic, and biomarker response beyond the primary endpoint in EXPLORER-HCM: results from a post hoc machine learning analysis

Abstract Introduction Mavacamten, a first-in-class selective inhibitor of cardiac myosin, was demonstrated in EXPLORER-HCM (NCT03470545) to be superior to placebo in achieving a primary endpoint of either (1) a ≥1.5 mL/kg/min increase in peak oxygen consumption (pVO2) and at least one New York Heart Association (NYHA) class reduction, or (2) a ≥3.0 mL/kg/min pVO2 increase without NYHA class worsening, in adults with obstructive hypertrophic cardiomyopathy (oHCM). However, the observed benefits of mavacamten were broader than the primary endpoint, suggesting a complex effect of the drug beyond improvements in these two parameters. Purpose A post hoc investigation of mavacamten clinical effects beyond the primary endpoint of EXPLORER-HCM. Methods EXPLORER data at week 30 were analyzed to evaluate improvements from baseline in primary (specified above), secondary (e.g. postexercise left ventricular outflow tract gradient and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score) and exploratory endpoints (e.g. circulating NT-ProBNP and cardiac Troponin I). Responses were classified as improved or not improved based on published thresholds, clinical standards and analyses of the EXPLORER data. Patients were grouped according to their improvement status using unsupervised hierarchical clustering. Results The cluster analysis resulted in four main groups with the following trends (Table); Group 1 = patients who met the primary endpoint and showed improvement in secondary/exploratory endpoints; Group 2 = patients with improvement in secondary/exploratory endpoints who did not meet the primary endpoint; Group 3 = patients who met the primary endpoint without substantial secondary/exploratory endpoint responses; Group 4 = patients without appreciable improvement in any endpoint. A substantially larger proportion of patients in Group 1 received mavacamten compared with placebo (88% vs. 12%, respectively). A similar trend was observed in Group 2 patients who exhibited improvements in secondary/exploratory endpoints (85% mavacamten vs. 15% placebo). Group 3 consisted predominantly of placebo-treated patients who met the primary endpoint but had negligible responses to secondary/exploratory endpoints (5% mavacamten vs. 95% placebo). Group 4 consisted predominantly of placebo-treated patients without appreciable clinically relevant responses from this analysis (10% mavacamten vs. 90% placebo). Conclusions Mavacamten was associated with clinical improvements beyond the primary endpoint of EXPLORER-HCM and was predominantly accompanied by amelioration of other measures associated with oHCM pathophysiology. In contrast, most placebo-treated patients who met the primary endpoint did not exhibit improvement in the underlying pathophysiology. These findings suggest a potential underestimation of mavacamten clinical impact based on the primary endpoint and prompt a deeper examination of mavacamten efficacy in patients with oHCM based on other clinically relevant endpoints. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb

Effects of continuous aerobic training associated with resistance training on maximal and submaximal exercise tolerance, fatigue, and quality of life of patients post-COVID-19.

Background and PurposeDyspnea, fatigue, and reduced exercise tolerance are common in post‐COVID‐19 patients. In these patients, rehabilitation can improve functional capacity, reduce deconditioning after a prolonged stay in the intensive care unit, and facilitate the return to work. Thus, the present study verified the effects of cardiopulmonary rehabilitation consisting of continuous aerobic and resistance training of moderate‐intensity on pulmonary function, respiratory muscle strength, maximum and submaximal tolerance to exercise, fatigue, and quality of life in post‐COVID‐19 patients.MethodsQuasi‐experimental study with a protocol of 12 sessions of an outpatient intervention. Adults over 18 years of age (N = 26) with a diagnosis of COVID‐19 and hospital discharge at least 15 days before the first evaluation were included. Participants performed moderate‐intensity continuous aerobic and resistance training twice a week. Maximal and submaximal exercise tolerance, lung function, respiratory muscle strength, fatigue and quality of life were evaluated before and after the intervention protocol.ResultsCardiopulmonary rehabilitation improved maximal exercise tolerance, with 18.62% increase in peak oxygen consumption (VO2peak) and 29.05% in time to reach VO2peak. VE/VCO2slope reduced 5.21% after intervention. We also observed increased submaximal exercise tolerance (increase of 70.57 m in the 6‐min walk test, p = 0.001), improved quality of life, and reduced perceived fatigue after intervention.DiscussionPatients recovered from COVID‐19 can develop persistent dysfunctions in almost all organ systems and present different signs and symptoms. The complexity and variability of the damage caused by this disease can make it difficult to target rehabilitation programs, making it necessary to establish specific protocols. In this work, cardiopulmonary rehabilitation improved lung function, respiratory muscle strength, maximal and submaximal exercise tolerance, fatigue and quality of life. Continuous aerobic and resistance training of moderate intensity proved to be effective in the recovery of post‐COVID‐19 patients.

Abstract 13895: Impact of Coronary Revascularization on Cardiopulmonary Performance in Patients With Coronary Chronic Total Occlusion

Background: —CTO PCI represents the tip of iceberg in interventional cardiology, however owing to lack of enough data, there is still debate about its benefit. CPET combines measurement of gas indices with standard exercise and ECG parameters giving a comprehensive way for patient evaluation also there is plenty of data about its use in many cardiovascular diseases and about its prognostic value in many occasions. So we thought of using CPET in evaluating value of CTO PCI on various CPET parameters. Hypothesis: CTO PCI improves cardiopulmonary performance evaluated by CPET. Methods: fifty nine patients underwent successful CTO PCI and CPET at baseline and at12 month follow up, of whom nine patients had suboptimal results in control angiography which is a higher than usual incidence of re-stenosis, we compared the results of the CPET pre and post-PCI in both groups. Results: In patent group, CPET at follow up revealed a significant increase of peak oxygen consumption (Peak VO 2 ) (13.47±1.53 ml/kg/min vs. 17.84±0.99 ml/kg/min p &lt;0.0001), VO 2 at anaerobic threshold (AT) (11.63 ± 1.14 ml/kg/min vs. 10.35 ±1.01ml/kg/min ( p &lt; 0.0001), peak oxygen pulse ( 16.02 ±1.34 vs. 11.15 ± 1.36, p &lt; 0.0001) and significant increase in peak cardiac index (3.78 ± 0.5 vs. 2.98 ±0.6, p &lt; 0.0001). Also there was significant decrease of Peak VE/VCO 2 (32.98 ± 3.2 vs. 42.98 ± 6.2, p &lt; 0.0001).In patients with re-stenosis, CPET at follow up revealed a significant decrease of peak oxygen consumption (Peak VO 2 ) (13.36±1.48 ml/kg/min vs. 12.41±0.97 ml/kg/min, p =0.02) and a significant increase of Peak VE/VCO 2 (42.73 ± 4.33 vs. 43.27 ± 3.29, p =0.01)also there was worse numerical values of other parameters despite not being statistically significant. Conclusions: CTO revascularization improves cardiopulmonary performance assessed by CPET in addition patients with re-occlusion after successful procedure had worse parameters even than their own baseline. CPET can provide a way for non-invasive follow-up of patients after PCI and earlier detection of in-stent re-stenosis that is more common in CTO.

Promoting Exercise and Healthy Diet Among Primary Care Patients: Feasibility, Preliminary Outcomes, and Lessons Learned From a Pilot Trial With High Intensity Interval Exercise.

Physical activity and healthy diet are recognized as effective approaches for disease prevention. Controlled laboratory clinical trials support these approaches, yet minimal data exists supporting implementation of exercise as medicine within a healthcare setting.Objectives: To understand perception and barriers to exercise and nutrition from patients and physicians from a family medicine clinic (FMC) to inform the implementation of a laboratory-based exercise and nutrition lifestyle intervention (Phase I), and to determine the feasibility, adherence, and preliminary outcomes of implementing this lifestyle intervention into a FMC (Phase II).Methods: In phase I 10 patients and 5 physicians were interviewed regarding perceptions of exercise and nutrition practices. In phase II patients at risk for cardiovascular disease were enrolled into a lifestyle intervention (n = 16), within a FMC, manipulating diet and exercise. Cardiorespiratory fitness (CRF), body composition, and metabolic blood markers were completed at baseline, after the 12-week intervention, and at 24 weeks. Feasibility was defined by patients who completed the intervention and number of sessions vs. total available.Results: Prescribing high-intensity interval training and a meal replacement for 12 weeks in patients with at least one risk factor for cardiovascular disease, was shown to have moderate feasibility with 62.5% (n = 10) for patients completing the 12 week intervention, and poor feasibility for assessing effects 12 weeks after cessation of the intervention, with 50% (n = 5) participants returning. Tracking exercise electronically via FitBit had moderate fidelity (n = 9), with hardcopy logs yielding poor compliance (n = 6). This pilot study demonstrated preliminary effectiveness of this home-based approach for improving cardiorespiratory fitness with an average 4.31 ± 5.67 ml·kg·min−1 increase in peak oxygen consumption. Blood triglycerides and insulin were improved in 70% and 60% of the patients, respectively.Conclusions: Despite moderate feasibility, a home-based exercise and nutrition has the potential to be used as an effective approach for managing and mitigating cardiovascular disease risk factors. There were key lessons learned which will help to develop and adapt a larger scale lifestyle intervention into a clinical setting.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/study/NCT02482922, identifier NCT02482922.

Serotonin 1A agonist and cardiopulmonary improvements with whole-body exercise in acute, high-level spinal cord injury: A retrospective analysis

High-level spinal cord injury (SCI) can result in spinal and supraspinal respiratory control deficits leading to insufficient ventilatory responses to exercise and training-related adaptations. We hypothesized a serotonin agonist, known to improve respiratory function in animal models, would improve adaptations to whole-body functional electrical stimulation (FES) exercise training in patients with acute high-level SCI. We identified ten patients (< 2 years of injury with SCI from C4-T3) in our program who had performed six months of FES-row training while on the Buspirone, a serotonin 1A agonist (29 ± 17 mg/day), between 2012 and 2018. We also identified well-matched individuals who trained for six months but not on Buspirone ( n = 11). A peak incremental FES-rowing exercise test and resting pulmonary function test had been performed before and after training. Those on Buspirone demonstrated greater increases in peak oxygen consumption (VO 2 peak: +0.24 ± 0.23 vs. +0.10 ± 0.13 L/min, P = 0.08) and peak ventilation (VEpeak: +6.5 ± 8.1 vs. -0.7 ± 6.9 L/min, P < 0.05) compared to control. In addition, changes in VO 2 peak and VEpeak were correlated across all patients ( r = 0.63, P< 0.01), but most strongly in those on Buspirone ( r = 0.85, P < 0.01). Furthermore, changes in respiratory function correlated to increased peak tidal volume in the Buspirone group ( r > 0.66, P < 0.05). These results suggest Buspirone improves cardiorespiratory adaptations to FES-exercise training in individuals with acute, high-level SCI. The strong association between increases in ventilatory and aerobic capacities suggests improved respiratory function is a mechanism, however controlled studies are needed to determine if this preliminary finding is reproducible.

Dynamics of heart failure markers and cardiac reverse remodeling in patients receiving cardiac contractility modulation therapy

Aim . To assess the clinical course and cardiac reverse remodeling in patients with heart failure (HF) with reduced ejection fraction (HFrEF) receiving cardiac contractility modulation (CCM) therapy. Material and methods . Fifty-five patients (mean age, 53±11 years, 46 males) with NYHA class II-III HFrEF (ischemic etiology in 73% of patients), sinus rhythm, QRS 25% and <25%) and HF etiology. Results . CCM therapy was associated with a decrease in HF class (p<0,00004001), HF-related hospitalization rate (p<0,0001001), blood NTproBNP concentration (p<0,018), an increase in peak oxygen consumption during the first year (p<0,006011), as well as a decrease in LV volumes and a LVEF increase (p<0,0001001). The direction of these changes did not depend on the number of ventricular leads and LVEF. The presence of ischemic cardiomyopathy and old myocardial infarction did not affect the disease prognosis, but was associated with a lower change in LV volumes and NTproBNP during 24 months of CCM therapy. LVEF values were significantly higher in the group of patients with HFrEF not associated with coronary artery disease after 12 and 24 months of follow-up. Conclusion . In the group of patients with class II-III HFrEF, CCM therapy in most patients was associated with improved clinical and hemodynamic status, increased exercise tolerance, decreased HF-related hospitalization rate, positive echocardiographic and NTproBNP changes.

Serotonin 1A agonist and cardiopulmonary improvements with whole-body exercise in acute, high-level spinal cord injury: a retrospective analysis.

High-level spinal cord injury (SCI) can result in spinal and supraspinal respiratory control deficits leading to insufficient ventilatory responses to exercise and training-related adaptations. We hypothesized a serotonin agonist, known to improve respiratory function in animal models, would improve adaptations to whole-body functional electrical stimulation (FES) exercise training in patients with acute high-level SCI. We identified 10 patients (< 2years of injury with SCI from C4 to T3) in our program who had performed 6 months of FES-row training while on Buspirone (29 ± 17mg/day) between 2012 and 2018. We also identified well-matched individuals who trained for six months but not on Buspirone (n = 11). A peak incremental FES-rowing exercise test and resting pulmonary function test had been performed before and after training. Those on Buspirone demonstrated greater increases in peak oxygen consumption (VO2peak: + 0.24 ± 0.23 vs. + 0.10 ± 0.13 L/min, p = 0.08) and peak ventilation (VEpeak: + 6.5 ± 8.1 vs. -0.7 ± 6.9 L/min, p < 0.05) compared to control. In addition, changes in VO2peak and VEpeak were correlated across all patients (r = 0.63, p < 0.01), but most strongly in those on Buspirone (r = 0.85, p < 0.01). Furthermore, changes in respiratory function correlated with increased peak tidal volume in the Buspirone group (r > 0.66, p < 0.05). These results suggest Buspirone improves cardiorespiratory adaptations to FES-exercise training in individuals with acute, high-level SCI. The strong association between increases in ventilatory and aerobic capacities suggests improved respiratory function is a mechanism; however, controlled studies are needed to determine if this preliminary finding is reproducible.

Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial

Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2-4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (-36 mm Hg, 95% CI -43·2 to -28·1; p<0·0001), greater increase in pVO2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB -1·8, -2·4 to -1·2; p<0·0001). 34% more patients in the mavacamten group improved by at least one NYHA class (80 of 123 patients in the mavacamten group vs 40 of 128 patients in the placebo group; 95% CI 22·2 to 45·4; p<0·0001). Safety and tolerability were similar to placebo. Treatment-emergent adverse events were generally mild. One patient died by sudden death in the placebo group. Treatment with mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive hypertrophic cardiomyopathy. The results of this pivotal trial highlight the benefits of disease-specific treatment for this condition. MyoKardia.

Cardiovascular Remodeling Experienced by Real-World, Unsupervised, Young Novice Marathon Runners.

AimsMarathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate. We examine in detail the real-world cardiovascular remodeling response following competition in a first marathon.MethodsSixty-eight novice marathon runners (36 men and 32 women) aged 30 ± 3 years were investigated 6 months before and 2 weeks after the 2016 London Marathon race in a prospective observational study. Evaluation included electrocardiography, cardiopulmonary exercise testing, echocardiography, and cardiovascular magnetic resonance imaging.ResultsAfter 17 weeks unsupervised marathon training, runners revealed a symmetrical, eccentric remodeling response with 3–5% increases in left and right ventricular cavity sizes, respectively. Blood pressure (BP) fell by 4/2 mmHg (P < 0.01) with reduction in arterial stiffness, despite only 11% demonstrating a clinically meaningful improvement in peak oxygen consumption with an overall non-significant 0.4 ml/min/kg increase in peak oxygen consumption (P = 0.14).ConclusionIn the absence of supervised training, exercise-induced cardiovascular remodeling in real-world novice marathon runners is more modest than previously described and occurs even without improvement in cardiorespiratory fitness. The responses are similar in men and women, who experience a beneficial BP reduction and no evidence of myocardial fibrosis or persistent edema, when achieving average finishing times.

Passive Whole-Body Hyperthermia Increases Aerobic Capacity and Cardio-Respiratory Efficiency in Amateur Athletes

Objective: The research was carried out to test the influence of adaptation to passive whole body hyperthermia (PH) on physical capacity and cardio-respiratory efficiency in men-amateur athletes under the testing load of increasing intensity in laboratory thermal-neutral conditions. Twenty-eight amateur athletes (males, mean age 20.2 ± 2.1 y.o., game-based kinds of sports—football, handball, training experience—4 - 7 years) were randomized into two groups: experimental (14 people), who underwent 24 PH procedures, and control (14 people), who underwent 24 light training sessions in interval regime on elliptical gym apparatus. Results: Adaptation to PH was accompanied by moderate increase of aerobic efficiency and cardio-respiratory endurance in amateur athletes under thermally neutral conditions, while interval training in the control group showed no reliable changes in efficiency. Conclusion: A 10-week course of PH procedures leads to the increase of peak oxygen consumption, oxygen consumption at the level of anaerobic threshold, and heart efficiency (enhancement of oxygen pulse values), as well as efficiency of pulmonary ventilation and bronchial conductance, which we consider to be cross effects of adaptation to passive whole-body repetitive hyperthermia.

P6325Gas exchange improvements during exercise correlate with hemodynamic changes in heart failure patients with a left ventricular assist device

Abstract Background The implantation of left ventricular assist devices (LVAD) has established its role in therapy for patients with end stage heart failure. Benefits in survival as well as an improved quality of life, compared to optimized medical therapy (OMT) alone, has been proven. There are limited data in the literature on the metabolic changes during exercise in LVAD patients, and in most studies no increase in peak oxygen consumption on cardiopulmonary exercise test (CPET) could be shown early after surgery. However, recent data suggests an improvement in peak oxygen uptake (VO2) as a late effect after rehabilitation. To further investigate these findings we sought to analyse CPET data from patients before LVAD implantation as well as in the early and late follow up in correlation with hemodynamic changes at these times. Methods We collected and retrospectively analysed data of heart failure patients who had undergone LVAD implantation, and in whom a right heart catheterization, a cardiopulmonary exercise test and an echocardiography had been performed at time before, as well as 6 Months and 12 months after LVAD implantation, respectively. Results Data of 43 patients implanted with an LVAD between 2011 and 2017 were analysed. There was significant improvement in cardiac output (3,2 vs 4,3 L/min, p&lt;0,001) and VE/VCO2 slope (46 vs 38, p=0,001) 6 months after LVAD implant as well as a significant reduction in PCWP (26 vs 11 mmHg, p&lt;0,001), PAP mean (40 vs 22 mmHg, p&lt;0,001), RA mean (12 vs 8 mmHg, p=0,002) and PVR (4,2 vs 2,5 WU, p&lt;0,001). However, there was no significant increase in peak VO2 after 6 months. 12 months after LVAD implantation there were no further significant changes in cardiac output, intracardiac pressures or VE/VCO2 slope, which all remained similar to the 6 months follow up. However, at that point, a significant increase in peak VO2 was seen, compared to baseline (1060 vs 1410ml/min, p=0,001) and to 6 months after surgery (Figure 1). Conclusion Cardiac output increases in heart failure patients early after LVAD implantation. Consequently, permanent ventricular off loading results in the reduction of intracardiac pressures and improvement in the VE/VCO2 slope 6 months after surgery. However, a significant rise in peak oxygen consumption could only be noted 12 months after surgery, suggesting either a delayed long-term effect of improved hemodynamics or other causes such as enhanced mobility or training due to improved quality of life.

Increased Heart Rate Responsiveness after Heart Transplant is Associated with Increased Peak Oxygen Consumption and Treadmill Time in CPET

Introduction Chronotropic incompetence is very common after heart transplant. The extent to which it affects the functional capacity of heart transplant patients is unknown. We hypothesize that a higher heart rate responsiveness would be associated with improved peak oxygen uptake and may have long-term prognostic impact. Methods We performed a retrospective analysis of all patients who underwent heart transplantation and cardiopulmonary exercise testing (CPET) in the first post-transplant year at a single large academic center between the year 2000 and 2011. Peak VO2 and total exercise time were assessed by CPET. Heart rate responsiveness was defined as the difference between peak and resting heart rate during CPET. The association of heart rate responsiveness with peak VO2 and total exercise time was analyzed using multivariable linear regression, and survival analysis was performed via a cox proportional hazard model. Results CPET was performed at our institution in 271 patients during the first year post heart transplantation at a median of 2.3 months. Subjects were 82% male, age 55 (IQR 45-61) at time of CPET. After multivariate adjustment, each ten beat/min increase in heart rate responsiveness was associated with a 0.9 ml/kg/min increase in peak oxygen consumption (p Conclusions Chronotropic incompetence after heart transplant is associated with decreased functional capacity but is not a prognostic indicator of mortality after transplant.

Impact of cardiac resynchronization therapy on inflammatory biomarkers and cardiac remodeling: The paradox of functional and echocardiographic response

IntroductionResponse to cardiac resynchronization therapy (CRT) can currently be assessed by clinical or echocardiographic criteria, and there is no strong evidence supporting the use of one rather than the other. Reductions in B-type natriuretic peptide (BNP) and C-reactive protein (CRP) have been shown to be associated with CRT response. This study aims to assess variation in BNP and CRP six months after CRT and to correlate this variation with criteria of functional and echocardiographic response. MethodsPatients undergoing CRT were prospectively enrolled between 2011 and 2014. CRT response was defined by echocardiography (15% reduction in left ventricular end-systolic volume) and by cardiopulmonary exercise testing (10% increase in peak oxygen consumption) from baseline to six months after device implantation. ResultsA total of 115 patients were enrolled (68.7% male, mean age 68.6±10.5 years). Echocardiographic response was seen in 51.4% and 59.2% were functional responders. There was no statistical correlation between the two. Functional response was associated with a significantly greater reduction in BNP (-167.6±264.1 vs. -24.9±269.4 pg/ml; p=0.044) and CRP levels (-1.6±4.4 vs. 2.4±9.9 mg/l; p=0.04). Nonetheless, a non-significant reduction in BNP and CRP was observed in echocardiographic responders (BNP -144.7±260.2 vs. -66.1±538.2 pg/ml and CRP -7.1±24.3 vs. 0.8±10.3 mg/l; p>0.05). ConclusionAn increase in exercise capacity after CRT implantation is associated with improvement in myocardial remodeling and inflammatory biomarkers. This finding highlights the importance of improvement in functional capacity after CRT implantation, not commonly considered a criterion of CRT response.

Effects of Community-Based Exercise in Adults With Severe Burns: A Randomized Controlled Trial

ObjectiveTo investigate the efficacy of community-based exercise programs in the rehabilitation of adult patients with burns compared with standard of care (SOC). DesignRandomized controlled trial, with 2:1 randomization. SettingAssessments were performed in a hospital setting. The intervention was performed in a community setting. ParticipantsAdult patients (N=45) with ≥30% total body surface area burns were randomized to participate in a community-based exercise program (n=31) or SOC (n=14). Patient sampling was consecutive and referred. InterventionsThe community-based exercise program consisted of 12 weeks of exercise with a community-based trainer after hospital discharge. The SOC group did not receive exercise training. Main Outcome MeasuresChange in lean body mass index, peak torque, and peak oxygen consumption from discharge to 12 weeks postdischarge, presented as mean ± SE. ResultsThe community-based exercise program group showed a significant increase in peak oxygen consumption compared with SOC (community-based exercise program: Δ=7.723±1.522mL/kg/min, P=.0006; SOC: Δ=2.200±1.150mL/kg/min, P=.0765; community-based exercise program vs SOC, P=.0236). The community-based exercise program group exhibited a significant within group increase in lean body mass index (Δ=1.107±0.431kg/m2, P=.0003; SOC: Δ=1.323±0.873kg/m2, P=.2808). Both groups showed significant within-group increases in peak torque (community-based exercise program: Δ=35.645±7.566Nm, P=.0003; SOC: Δ=34.717±11.029Nm, P=.0082). No significant differences were noted between the 2 groups for lean body mass index or peak torque. ConclusionsPatients who participate in a community-based exercise program show significant improvements in cardiopulmonary fitness compared with SOC, supporting the use of a community-based exercise program as an alternative therapy to SOC in adults with severe burns.

Lung Ventilation Efficiency and Quality of Life After Orthotopic Heart Transplantation

The study involved 40 patients with terminal chronic heart failure (CHF) included in the waiting list for heart transplantation. Before surgery and after OHT all patients underwent cardiopulmonary exercise testing, evaluation of clinical status and quality of life (QL) according to the 36-Item Short Form Survey (SF-36). During the follow-up period (5 years) after OHT there were a significant increase in physical capacity, two-fold increase of peak oxygen consumption (VO2), normalization of VE/VCO2 slope level, improvement of the efficiency of the VO2 recovery within first minute and reduction of the VO2 recovery time. OHT was associated with significant improvement of physical and mental health components of QL. Among exercise test parameters significantly associated with improved physical health component of QL were increments in exercise capacity, peak VO2, rate of VO2 recovery within first minute. There was no relationship between cardiopulmonary parameters of exercise test and mental health component of QL. In patients with terminal CHF OHR led to significant increase of the lung ventilation efficiency and QL. Factors contributing to QL improvement after OHT were augmentation of left ventricular ejection fraction and reduction of CHF NYHA class. Among cardiopulmonary exercise test parameters, a high predictive value relative to improvement of subjective assessment of physical health component of QL showed exercise capacity, peak VO2, and efficiency of VO2 recovery within first minute.