Role of Exercise in Pulmonary Hypertension: Evidence from Bench to Bedside.

Background: Pulmonary hypertension (PH) is a debilitating condition characterized by elevated pulmonary arterial pressure and progressive vascular remodelling, leading to exercise intolerance. The progression of PAH is regulated at a cellular and molecular level which influences various physiological processes. Exercise plays an important role in improving function in PH. Although the signalling pathways that regulate cardio-protection through exercise have not been fully understood, the positive impact of exercise on the various physiological systems is well established. Summary: Exercise has emerged as a potential adjunctive therapy for PH, with growing evidence supporting its beneficial effects on various aspects of the disease pathophysiology. This review highlights the contributions of cellular and molecular pathways and physiological processes to exercise intolerance. Preclinical studies have provided insight into the mechanisms underlying exercise-induced improvements in PH which are modulated through improvements in endothelial function, inflammation, oxidative stress, and mitochondrial function. Along with preclinical studies, various clinical studies have demonstrated that exercise training can lead to significant improvements in exercise capacity, haemodynamics, quality of life, and functional status. Moreover, exercise interventions have been shown to improve skeletal muscle function and enhance pulmonary vascular remodelling, contributing to overall disease management. Further research efforts aimed at better understanding the role of exercise in PH pathophysiology, and refining exercise interventions are warranted to realize its full potential in the management of this complex disease. Key Messages: Despite the promising benefits of exercise in PH, several challenges remain, including the optimal intensity, duration, and type of exercise training, as well as patient selection criteria and long-term adherence. Additionally, the mechanisms underlying the observed improvements require further elucidation to optimize exercise protocols and personalize treatment strategies. Nonetheless, exercise represents a promising therapeutic approach that can complement existing pharmacological therapies and improve outcomes in PH patients.

Challenges and solutions to implementing cardiac rehabilitation in a low- and middle-income country.

BACKGROUND: Cardiac rehabilitation (CR) remains greatly underutilized, especially in low- and middle-income countries (LMIC). It is therefore important to explore factors that contribute to this, as perceived by health-care professionals (HCPs). RESEARCH DESIGN AND METHODS: This was a qualitative study using in-depth interviews that enrolled 18 HCPs (i.e. six each of physicians, physiotherapists, and nurses; mean experience in CR: 17.9 ± 11.8 yrs) working in cardiovascular care, and CR across private and government hospitals (both teaching and non-teaching) in India. RESULTS: The main challenges were related to lack of referrals, perceived lack of benefit from CR, poor infrastructure within hospitals and health systems, and differences in practice. The perceived inadequacies were lack of competencies in CR, limited task sharing strategies, and ineffective utilization of existing human resources. Devising strategies to improve awareness and competencies, facilitating task sharing, and remodeling holistic care with an active CR component may be beneficial to facilitate greater implementation of CR in India. CONCLUSIONS: Challenges, inadequacies, and solutions to implementing CR have been explored by involving various HCPs commonly involved in delivering CR across different health systems in a LMIC. TRIAL REGISTRATION: www.ctri.nic.in with identifier CTRI/2020/07/026807.

Exercise Training in Pulmonary Hypertension: AN UPDATED SYSTEMATIC REVIEW WITH META-ANALYSIS.

PURPOSE: Given that previous reviews on exercise training in pulmonary hypertension (PH) were largely based on a small number of randomized controlled trials (RCT), their conclusions are subject to bias. This review sought to identify the impact of exercise training on functional capacity and health-related quality of life (HRQoL) in PH using advanced statistical approaches such as meta-analysis by stratification according to study design. REVIEW METHODS: Five databases were searched from January 2015 to April 2020 to update a previous review. Included articles had data extracted, risk of bias (ROB) assessed, and quality rating performed. Data were analyzed using meta-analysis with a random-effects model for 6-min walk test (6MWT) distance and HRQoL. Heterogeneity was explored using stratified meta-analysis, within patient correlation and meta-regression. RESULTS: A total of 28 studies (11 RCT, 12 pre-/post-studies, 2 two-group non-RCT, and three case series) consisting of 1264 patients were included. Meta-analysis of six RCT demonstrated an improved 6MWT distance by 49.5 m (95% CI, 27.2-71.8: I2 = 73%; 254 participants; low-moderate ROB) with a low correlation coefficient of 0.34, while the 12 pre-/post-non-RCT showed an improvement of 68.69 m (95% CI, 50.50-86.69: I2 = 36%; 784 participants; high ROB) along with improvements in V˙ o2peak (weighted mean difference [WMD] = 3.03 mL/kg/min, 95% CI, 2.17-3.90: I2 = 0%, P = .82), and HRQoL (WMD = 2.74: 95% CI, -0.82 to 6.30). Metaregression showed that the benefit of exercise on 6MWT distance did not significantly vary across the trial study characteristics. CONCLUSION: This updated review identified an additional body of evidence supporting the efficacy of exercise training on 6MWT distance and HRQoL in stable PH patients. These benefits appeared to be consistent across models of delivery.

Prevalence of sarcopenia in heart failure: A systematic review.

OBJECTIVE: Heart Failure (HF) is emerging as a crucial factor promoting muscle wasting and dysfunction contributing to sarcopenia. This modulates disease severity and reduces exercise capacity and leading to poorer outcomes. Therefore, we aimed to systematically investigate the overall prevalence of sarcopenia in HF. METHODS: An electronic search was carried out in selected databases until 21st January, 2021. Data was pooled from the included articles and represented as pooled prevalence of sarcopenia. Subgroup analysis was undertaken between methods of diagnosis of sarcopenia, gender, ejection fraction, median time point and geographical region. RESULTS: Amongst 32,643 citations imported from selected databases, 12 articles were included in final analysis. Analysis for prevalence of sarcopenia was 34%, with prevalence rates ranging from 10.1% to 68%. Subgroup analysis revealed strong associations between Dual-energy X-ray Absorptiometry (DXA) and Asian Working Group for Sarcopenia (AWGS) (chi square = 3.24; p < 0.001), with a good level of agreement (kappa = 0.76 [95% CI: 0.70-0.82]; p < 0.001). Gender wise analysis revealed higher prevalence of sarcopenia among males (66%) than females (34%). CONCLUSION: Sarcopenia is highly prevalent among those with HF (irrespective of type of HF) and is more commonly seen in males compared to females.

Technology-based Comprehensive Cardiac Rehabilitation Therapy (TaCT) for women with cardiovascular disease in a middle-income setting: A randomized controlled trial protocol.

Women are underrepresented in cardiac rehabilitation (CR) despite the benefits, and this is exacerbated in lower-resource settings where CR is insufficiently available. In this randomized controlled trial, the effectiveness of the Technology-based Comprehensive Cardiac Rehabilitation Therapy (TaCT) electronic cardiac rehabilitation (eCR) intervention on functional capacity, risk factors, quality of life, heart-health behaviors, symptoms, and morbidity will be tested among women with CVD in a middle-income country. Following a pilot study, a single-center, single-blinded, 2 parallel-arm (1:1 SNOSE) superiority trial comparing an eCR intervention (TaCT) to usual care, with assessments pre-intervention and at 3 and 6 months will be undertaken. One hundred adult women will be recruited. Permuted block (size 10) randomization will be applied. The 6-month intervention comprises an app, website, SMS texts with generic heart-health management advice, and bi-weekly 1:1 telephone calls with a nurse trainee. Individualized exercise prescriptions will be developed based on an Incremental Shuttle Walk Test (primary outcome) and dietary plans based on 24 h dietary recall. A yoga/relaxation video will be provided via WhatsApp, along with tobacco cessation support and a moderated group chat. At 3 months, intervention engagement and acceptability will be assessed. Analyses will be conducted based on intent-to-treat. If results of this novel trial of women-focused eCR in a middle-income country demonstrate clinically-significant increases in functional capacity, this could represent an important development for the field considering this would be an important outcome for women and would translate to lower mortality.

Identifying the Optimal Exercise Prescription for Patients with Coronary Artery Disease Undergoing Cardiac Rehabilitation: Protocol for a Systematic Review and Network Meta-Analysis of Randomized Control Trials.

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity. Exercise-based cardiac rehabilitation (EBCR) has been shown to improve clinical outcomes in these patients, and yet clinicians are often challenged to prescribe the most effective type of exercise training. Therefore, this systematic review and network meta-analysis (NMA) aims to formally quantify the optimal dose of exercise training interventions to improve exercise capacity and quality of life by undertaking direct and indirect pooled comparisons of randomized controlled trials. A detailed search will be conducted on PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), EMBASE and Web of Science. Two reviewers will screen the existing literature and assess the quality of the studies. Disagreements will be resolved through consensus. We anticipate that the analysis will include pairwise and Bayesian network meta-analyses. Most of the trials have studied the impact of exercise training comparing one or two modalities. As a result, little evidence exists to support which interventions will be most effective. The current NMA will address this gap in the literature and assist clinicians and cardiac rehabilitation specialists in making an informed decision. Results will be disseminated through peer-reviewed journals. Ethical approval is not applicable, as no research participants will be involved. PROSPERO Registration number: CRD42022262644.

A multicentric, 2 × 2 factorial, randomised, open-label trial to evaluate the clinical effectiveness of structured physical activity training and cognitive behavioural therapy versus usual care in heart failure patients: a protocol for the PACT-HF trial.

Background: Heart failure (HF) is a multi-morbid chronic condition, which adversely affects the quality of life of the affected individual. Engaging the patient and their caregivers in self-care is known to reduce mortality, rehospitalisation and improve quality of life among HF patients. The PACT-HF trial will answer whether clinical benefits in terms of mortality and hospitalisation outcomes can be demonstrated by using a pragmatic design to explore the specific effects of physical activity, and cognitive behavioural therapy in HF patients in India. Methods: We will conduct a 2 × 2 factorial, randomized, open-label trial, which aims to see if rehabilitation strategies of structured physical activity training and cognitive behavioural therapy for depression and self-management reduce the risk of repeat hospitalisation and deaths in HF patients in India. Patients will be randomised to (1) physical activity + usual care (2) cognitive behaviour therapy + usual care, (3) physical activity + cognitive behaviour therapy + usual care, and (4) usual care at 1:1:1:1 ratio. Time to mortality will be the primary outcome. A composite of mortality and hospitalisation for HF will be the main secondary outcome. Additional secondary outcomes will include 'days alive and out of hospital', cumulative hospitalisation, quality of life, Minnesota Living with Heart Failure questionnaire score, depression score, six minutes walking distance, handgrip strength, and adherence to medicines and lifestyle.  The effects of intervention on the primary outcome will be estimated from Cox proportional hazard models. For the continuous secondary outcome variables, differences between randomised groups will be estimated from linear mixed models or generalised estimating equations (GEE) as appropriate. Discussion: PACT-HF is designed to provide reliable evidence about the balance of benefits and risks conferred by physical activity and cognitive behavioural therapy-based cardiac rehabilitation for those with HF, irrespective of their initial disease severity.

Post pandemic research priorities: A consensus statement from the HL-PIVOT.

We have been amid unhealthy living and related chronic disease pandemics for several decades. These longstanding crises have troublingly synergized with the coronavirus disease 2019 (COVID-19) pandemic. The need to establish research priorities in response to COVID-19 can be used to address broad health and wellbeing, social and economic impacts for the future is emerging. Accordingly, this paper sets out a series of research priorities that could inform interdisciplinary collaboration between clinical sciences, public health, business, technology, economics, healthcare providers, and the exercise science/sports medicine communities, among others. A five-step methodology was used to generate and evaluate the research priorities with a focus on broad health and well-being impacts. The methodology was deployed by an international and interdisciplinary team from the Healthy Living for Pandemic Event Protection (HL- PIVOT) network. This team were all engaged in responding to the Pandemic either on the 'front-line' and/or in leadership positions ensuring the currency and authenticity of the process. Eight research priorities were identified clustered into two groups: i) Societal & Environmental, and ii) Clinical. Our eight research priorities are presented with insight from previously published research priorities from other groups.

Exercise training in cardiac rehabilitation: Setting the right intensity for optimal benefit.

Cardiac rehabilitation (CR) programs are recommended standard-of-care by all major cardiovascular medicine professional organizations. Exercise training is the cornerstone for CR, with aerobic training being the primary form of training. The benefits of exercise training are multiple; however, improved cardiorespiratory fitness is of utmost importance. Moderate-intensity continuous training, supplemented with resistance training, has traditionally been the most common form of exercise training in CR. This review discusses the role of aerobic exercise training in CR and the importance of effective and personalized exercise prescription for optimized results. We also focus on the benefits and utility of high-intensity interval training across different clinical populations commonly seen in the CR setting.

Defining the importance of stress reduction in managing cardiovascular disease - the role of exercise.

Traditional risk factors for cardiovascular disease (CVD) have long been the focus of preventive strategies. The impact of family stress, depression, anxiety, hostility, pessimism, job strain, social isolation, lack of purpose in life and social support, are well recognized risks for CVD development, however they are under-appreciated in clinical practice guidelines. The purpose of this article is to review the impact of acute and chronic stress on CVD risk, elaborate repositioning in guidelines, with emphasis to approaches for stress reduction. Regular exercise, both aerobic and resistance, leads to better adaptiveness to other types of stress, however, it remains unknown whether the total amount of stress one can receive before negative health effects is unlimited. Evidently, marked reductions in stress related disorders are shown following formal cardiac rehabilitation programs. Attendance of cardiac rehabilitation is highly recommended for the stress-related mortality risk reduction. Innovative approaches to offset the broad challenges that CVD pose, augmented by sustained exposure to stress, are desperately needed, but hindered by a lack of successful population-level interventions that promote lasting change.

Development of the International Cardiac Rehabilitation Registry Including Variable Selection and Definition Process.

Introduction: The International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) is developing a registry (ICRR) specifically for low-resource settings, where the burden of cardiovascular diseases is greatest and the need for program development highest. Herein we describe the development process, including the variable selection process. Method: Following a literature search on registry best practices, a stepwise model for ICRR development was identified. Then, based on recommendations by Core Outcome Set-STAndards for Development (COS-STAD), we underwent a process to identify variables. All available CR registries were contacted to request their data dictionaries, reviewed CR quality indicators and guideline recommendations, and searched for common data elements and core outcome sets; 35 unique variables (including patient-reported outcomes) were selected for potential inclusion. Twenty-one purposively-identified stakeholders and experts agreed to serve on a Delphi panel. Panelists rated the variables in an online survey, and suggested potential additional variables; A webcall was held to reach consensus on which to include/exclude. Next, panelists provided input to finalize each variable definition, and rated which associated indicators should be used for benchmarking in registry dashboards and a patient lay summary; a second consensus call was held. A 1-month public comment period ensued. Results: First, registry objectives and governance were approved by ICCPR, including data quality and access policies. The protocol was developed, for public posting. For variable selection, the overall mean rating was 6.1 ± 0.3/7; 12 were excluded, some of which were moved to a program survey, and others were revised. Two variables were added in an annual follow-up, resulting in 13 program and 16 patient-reported variables. Legal advice was sought to finalize ICRR agreements. Ethics approvals were obtained. Usability testing is now being initiated. Conclusion: It is hoped this will serve to harmonize CR assessment internationally and enable quality improvement in CR delivery in low-resource settings.

Building Capacity Through ICCPR Cardiovascular Rehabilitation Foundations Certification (CRFC): EVALUATION OF REACH, BARRIERS, AND IMPACT.

PURPOSE: The International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) developed an online Cardiovascular Rehabilitation Foundations Certification (CRFC; https://globalcardiacrehab.com/Certification) in October 2017, to build cardiac rehabilitation (CR) delivery capacity in low-resource settings based on their guidelines. Herein we evaluate its reach globally, barriers to its completion, as well as satisfaction and impact of the course among those completing it. METHODS: The country of origin of all applicants was tallied. An online survey was developed for learners who completed the CRFC (completers), and for those who applied but did not yet complete the program (noncompleters), administered using Google Forms. RESULTS: With regard to reach, 236 applications were received from 23/203 (11%) countries in the world; 51 (22%) were from low- or middle-income countries. A total of 130 (55%) have completed the CRFC; mean scores on the final examination were 88.3 ± 7.1%, with no difference by country income classification (P= .052). Sixteen (22%) noncompleters and 37 (34%) completers responded to the survey. Barriers reported by noncompleters were time constraints, cost, and technical issues. Overall satisfaction (scale 1-5) with the CRFC was high (4.49 ± 0.51); most completers would highly recommend the CRFC to others (4.30 ± 0.66), and perceived that the information provided will contribute to their work and/or the care of their patients (4.38 ± 0.89); 29 (78%) had used the information from the CRFC in their practice. CONCLUSIONS: The reach of the CRFC still needs to be broadened, in particular in low-resource settings. Learners are highly satisfied with the certification, and its impacts on CR practice are encouraging. Input has been implemented to improve the CRFC.

Developing a Complex Understanding of Physical Activity in Cardiometabolic Disease from Low-to-Middle-Income Countries-A Qualitative Systematic Review with Meta-Synthesis.

Physical activity behaviour is complex, particularly in low-resource settings, while existing behavioural models of physical activity behaviour are often linear and deterministic. The objective of this review was to (i) synthesise the wide scope of factors that affect physical activity and thereby (ii) underpin the complexity of physical activity in low-resource settings through a qualitative meta-synthesis of studies conducted among patients with cardiometabolic disease living in low-to-middle income countries (LMIC). A total of 41 studies were included from 1200 unique citations (up to 15 March 2021). Using a hybrid form of content analysis, unique factors (n = 208) that inform physical activity were identified, and, through qualitative meta-synthesis, these codes were aggregated into categories (n = 61) and synthesised findings (n = 26). An additional five findings were added through deliberation within the review team. Collectively, the 31 synthesised findings highlight the complexity of physical activity behaviour, and the connectedness between person, social context, healthcare system, and built and natural environment. Existing behavioural and ecological models are inadequate in fully understanding physical activity participation in patients with cardiometabolic disease living in LMIC. Future research, building on complexity science and systems thinking, is needed to identify key mechanisms of action applicable to the local context.

Impacts of the COVID-19 Pandemic on Cardiac Rehabilitation Delivery around the World.

Background: We investigated impacts of COVID-19 on cardiac rehabilitation (CR) delivery around the globe, including virtual delivery, as well as effects on providers and patients. Methods: In this cross-sectional study, a piloted survey was administered to CR programs globally via REDCap from April to June 2020. The 50 members of the International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) and personal contacts facilitated program identification. Results: Overall, 1062 (18.3% program response rate) responses were received from 70/111 (63.1% country response rate) countries in the world with existent CR programs. Of these, 367 (49.1%) programs reported they had stopped CR delivery, and 203 (27.1%) stopped temporarily (mean = 8.3 ± 2.8 weeks). Alternative models were delivered in 322 (39.7%) programs, primarily through low-tech modes (n = 226,19.3%). Furthermore, 353 (30.2%) respondents were re-deployed, and 276 (37.3%) felt the need to work due to fear of losing their job, despite the perceived risk of contracting COVID-19 (mean = 30.0% ± 27.4/100). Also, 266 (22.5%) reported anxiety, 241(20.4%) were concerned about exposing their family, 113 (9.7%) reported increased workload to transition to remote delivery, and 105 (9.0%) were juggling caregiving responsibilities during business hours. Patients were often contacting staff regarding grocery shopping for heart-healthy foods (n = 333, 28.4%), how to use technology to interact with the program (n = 329, 27.9%), having to stop their exercise because they have no place to exercise (n = 303, 25.7%), and their risk of death from COVID-19 due to pre-existing cardiovascular disease (n = 249, 21.2%). Respondents perceived staff (n = 488, 41.3%) and patient (n = 453, 38.6%) personal protective equipment, as well as COVID-19 screening (n = 414, 35.2%), and testing (n = 411, 35.0%) as paramount to in-person service resumption. Conclusion: Given the estimated number of CR programs globally, these results suggest approximately 4400 CR programs globally have ceased or temporarily stopped service delivery. Those that remain open are implementing new technologies to ensure their patients receive CR safely, despite the challenges. Highlights: - COVID-19 has impacted cardiac rehabilitation (CR) delivery around the globe.- In this cross-sectional study, a survey was completed by 1062 (18.3%) CR programs from 70 (63.1%) countries.- The pandemic has resulted in at least temporary cessation of ~75% of CR programs, with others ceasing initiation of new patients, reducing components delivered, and/or changing of mode delivery with little opportunity for planning and training.- There is also significant psychosocial and economic impact on CR providers.- Alternative CR model (e.g., home-based, virtual) reimbursement advocacy is needed, to ensure safe, accessible secondary prevention delivery.