Heart failure (HF) remains a major global health challenge, particularly in low-resource settings where access to comprehensive cardiac rehabilitation (CR) is limited. Yoga, a culturally contextualised mind-body intervention, holds promise as an adjunctive therapy in CR. The Yoga-EndOmics study aims to evaluate the effects of Yoga-based cardiac rehabilitation (Yoga-CaRe) on gene expression, endothelial function, vascular biomarkers and clinical outcomes in systolic HF, providing mechanistic insights into its potential integration into conventional cardiac rehabilitation.

This is a prospective, randomised, open-label, blinded-endpoint (PROBE) mechanistic trial enrolling 78 patients with HF with reduced ejection fraction (HFrEF). Participants will be randomised in a 1:1 ratio to receive either a structured Yoga-CaRe intervention or enhanced standard care for 3 months. The Yoga-CaRe group will attend 20 supervised sessions with guided home practice involving tailored asanas, pranayama and meditation. Primary outcomes are changes in endothelial-dependent flow-mediated dilation (FMD) and functional exercise capacity at 3 months. Secondary outcomes include changes in arterial compliance and stiffness, circulating biomarkers of endothelial dysfunction, oxidative stress and inflammation, and immediate changes in global gene expression profiles in peripheral blood mononuclear cells following the Yoga-CaRe intervention. Data will be analysed using analysis of covariance (ANCOVA) for between-group comparisons and significant analysis of microarray (SAM) for global gene expression profiles.

The study has received ethical clearance from the Institutional Ethics Committee of the SDM College of Medical Sciences and Hospital, India (SDMIEC/2025/1072) and is registered with the Clinical Trials Registry of India. Findings will be disseminated through peer-reviewed journals, scientific conferences and stakeholder engagement platforms to inform future integrative strategies in HF management.

CTRI/2023/12/060758

Multimorbidity or multiple long-term conditions (MLTCs) are defined as the coexistence of two or more chronic conditions in an individual. With increased longevity and the rising burden of chronic non-communicable diseases (NCDs), multimorbidity is becoming the norm. Although more prevalent in older populations and people with low socio-economic status, multimorbidity is rapidly rising in the younger age groups. Accurate data on its incidence and health and economic impacts, ie, disability-adjusted life years (DALY) lost and quality-adjusted life year (QALY) are not available for the Indian population. The objective of this study is to determine the incidence and predictors of multimorbidity, the longitudinal trends, the common clusters of conditions and the health and economic impact of multimorbidity among adult Indians aged ≥40 years.

12 229 participants (≥40 years) from the population-based cohort, titled the Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) cohort, from Delhi and Chennai will be recruited. CARRS is an existing adult urban cohort which is well characterised, deeply phenotyped and geocoded with bio-banked samples. They will be followed up longitudinally twice during 2023–2025. Information will be collected on common NCD risk factors (physical inactivity, tobacco and alcohol use), disability, frailty and treatment costs. We will also perform anthropometric and blood pressure measurements on all participants as well as biomarker assessments on a sub-sample of 2300.

Ethics approval has been obtained from the ethics committees of the Centre for Chronic Disease Control (CCDC) (Institutional Review Board (IRB) 00006330) and the Madras Diabetes Research Foundation (IRB no. IRB00002640). Key findings from the study will be published in national and international peer-reviewed journals. Results will also be presented at various academic conferences to engage with the broader research community. A final report will be submitted to the funding agency upon completion of the fellowship. De-identified data will be securely stored at the CCDC. Access to the data will be available upon request to the principal investigator.

Guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF) reduces morbidity and mortality and remains widely underused. An HFrEF polypill containing all four pillars of GDMT has been proposed as an implementation strategy to improve GDMT treatment rates and subsequent patient outcomes. We present the design and protocol for a proof-of-concept, pilot type I hybrid randomised clinical trial evaluating an HFrEF polypill compared with usual care among patients with HFrEF in Sri Lanka to evaluate short-term feasibility.

This multi-centre, open-label, pilot type I hybrid randomised clinical trial will recruit 40 adults with HFrEF from two public hospital sites in Colombo, Sri Lanka. Participants will be randomised to an HFrEF polypill (containing bisoprolol, losartan, eplerenone, and dapagliflozin in three available strengths) or usual care and followed for 4 weeks. The primary outcome is feasibility of recruitment measured by recruitment rate and adherence to study protocols measured by completion rate of study-related procedures. Other key outcomes include adherence to GDMT and assessment of serious adverse events among other exploratory outcomes.

The study has been approved by the ethics review committee at the Faculty of Medicine, University of Kelaniya (Sri Lanka), the institutional review board at Washington University in St. Louis (United States), and the National Medicines Regulatory Authority (Sri Lanka). The findings of this pilot trial will inform the design and implementation of a future large-scale type I hybrid trial to assess the efficacy and safety of an HFrEF polypill in improving clinical outcomes.

Sri Lanka Clinical Trials Registry (SLCTR/2024/003); ClinicalTrials Registry (NCT06831864).