Identification of novel endogenous control miRNAs in heart failure for normalization of qPCR data.

MicroRNAs (miRNAs), a class of non-coding RNAs, are utilized as biomarkers for a wide range of disorders. Circulating miRNAs are proposed as potential markers in the clinical identification of heart failure (HF). However, identifying miRNA biomarkers in HF requires identification of robust endogenous control miRNAs for normalization in differential expression analysis. Hence, this study aimed to identify circulating miRNAs that can be utilized as endogenous controls in HF. We evaluated the expression of eight miRNAs, which were previously reported as endogenous controls in different pathological conditions. Total RNA, including miRNA, was extracted from the serum samples of 30 HF patients (15 HFrEF and 15 HFpEF) and their matched controls (n = 15). We used quantitative PCR to determine the miRNA expression. The stability of the selected endogenous miRNAs was assessed and compared using a standard set of criteria with the RefFinder software. Six of the eight miRNAs analyzed showed consistent expression among all sample groups. Stability analysis ranked hsa-let-7i-5p, hsa-miR-148b-3p, and hsa-miR-484 as the most stable miRNAs, indicating their potential as reliable endogenous controls.

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.

Assessment of the impact of heart failure on household economic well-being: a protocol.

Background: Heart failure (HF), which is an emerging public health issue, adversely affects the strained health system in India. The adverse impact of HF on the economic well-being has been narrated in various anecdotal reports from India, with affected individuals and their dependents pushed into the vicious cycle of poverty. There is limited research quantifying how HF impacts the economic well-being of households from low- and middle-income countries. Methods: We describe the methods of a detailed economic impact assessment of HF at the household level in India. The study will be initiated across 20 hospitals in India, which are part of the National heart Failure Registry (NHFR). The selected centres represent different regions in India, stratified based on the prevailing stages of epidemiological transition levels (ETLs). We will collect data from 1800 patients with acute decompensated HF and within 6-15 months follow-up from the time of initial admission. The data that we intend to collect will consist of a) household healthcare expenditure including out-of-pocket expenditure, b) financing mechanisms used by households and (c) the impoverishing effects of health expenditures including distress financing and catastrophic health expenditure. Trained staff at each centre will collect data by using a validated and structured interview schedule. The study will have 80% power to detect an 8% difference in the proportion of households experiencing catastrophic health expenditures between two ETL groups.  After considering a non-response rate of 5%, the target sample size is approximately 600 patients from each group and the total sample size is 1800 patients. Potential Impact: Our study will provide information on catastrophic health spending, distress financing and household expenditure in heart failure patients. Our findings will help policy makers in understanding the micro-economic impact of HF in India and aid in allocation of appropriate resources for prevention and control of HF.