A factorial randomized trial of structured physical activity training and brief cognitive behavioral therapy for depression and self-management for prevention of repeat hospital admission and death among acute decompensated heart failure patients.

Cardiovascular disease (CVD is the leading cause of mortality and morbidity in India. Although heart failure (HF) is a leading contributor to CVD mortality, data are notavailable to calculate the burden attributable to HF with high precision in India. However,available estimates suggest that up to 23 million (HF) cases are prevalent in India.Additionally, the upper estimate of the annual incidence of HF in India is at 1.8 millioncases2. The ischemic heart disease prevalence is rising in India and this may furtherincrease HF incidence and prevalence in future. Additionally, admissions due to HF areprojected to rise by 50% over the next 10 years, largely due to ageing of the population.

Heart failure requires resource intensive treatment strategies and despite the availabletreatment options mortality rate are very high. For example, the HF registry data clearlydemonstrate that the first-year mortality after an acute decompensated heart failureadmission in Kerala is around 30%.3 The three-year mortality has been also estimated as45%.4 As adjunct therapy along with evidence based medicines, cardiac rehabilitationprogrammes are found to be helpful in reducing the mortality and morbidity associatedwith HF.

Based on available evidence, exercise-based cardiac rehabilitation (CR) has beenrecommended as an effective and safe adjunct in the management of HF. An updatedCochrane review shows that improvements in hospitalisation and health-related qualityof life with exercise-based cardiac rehabilitation appear to be consistent across patientsregardless of the components of the programme characteristics and may reduce mortalityin the longer term.

The association between depression and heart failure has been demonstrated innumerous studies. Depression is characterised by symptoms that affect a patient’scognitive, emotional and behavioural processes. Data suggest that up to 60% of HFpatients are suffering from various grades of depression and may benefit from cognitivebehavioural therapy.6 The existence of depression has negative implications for HFpatients, particularly through reduced survival and an increased risk of secondary events.The behavioural influences of depression also reduce the likelihood of both treatmentadherence and modification in lifestyle behaviours. It will also affect their ability for selfmanagement,which is very crucial in HF. Cognitive behavioural therapy is a well-established intervention in depression but its effectiveness for depression in heart failurepatients remains unclear especially in patients from low and middle-income countries.

The aim of our proposed trial is to see if rehabilitation strategies of structured physicalactivity training and brief cognitive behavioural therapy for depression and selfmanagementreduces the risk of repeat hospitalisation and deaths in HF patients in India.

Methods

Study settings and population: The study will be carried out in hospital settings with
facilities for management of heart failure.

Study Design: We propose an investigator-initiated, factorial, multicentre, randomised
controlled trial. Physician diagnosed HF patients will be recruited and randomised to
either a structured physical activity-training programme or usual rehabilitation care, and
to either a structured brief cognitive behavioural therapy session or usual care (Figure 1).
Follow-up will be for an average of 3 years.

Primary outcome: Time to mortality will be the primary outcome for the proposed study.Cumulative hospital admission rate will be considered as the main secondary outcome.Additional secondary outcome variable will include quality of life, Minnesota Living with Heart Failure questionnaire score, depression score, six minutes walking distance,handgrip strength, and adherence to medicines and lifestyle.

Sample size: Assuming a three-year cumulative event rate of 50% or more for theprimary outcome (mortality) it was estimated that a sample size of 1632 participantswould provide 80% power to detect at least 20% reduction in the relative risk of eachof the primary outcomes for each of the randomised comparisons.

Identification of study subjects: The study will be conducted in six hospitals with thecapacity to recruit a minimum of 300 HF patients in one year. Consecutive patientswith heart failure will be invited to participate in the study.

Interventions: A structured exercise-training programme will be developed and will beintroduced in the hospital outpatient settings. A non-physician health worker willdeliver the exercise training. The exercise training will be given three times in the outpatientsettings during the first three months and thereafter once in every threemonths. Additionally, a mobile app will be developed to introduce home basedexercise training and will be given to the participants in the exercised based cardiacrehabilitation intervention arm.

Cognitive behavioural therapy intervention will consist of group, face-to-facesessions that will be delivered by a non-physician health care worker. The identifiednon-physician worker will be trained to impart training based on a structuredbehavioural therapy programme. The behavioural therapy will be relatively brief and of20-30 minutes duration. Intervention arm participants will receive one individual faceto-face session initially and thereafter group sessions once in a month for the firstthree months. After three months, the group sessions will be conducted once in threemonths. The behavioural therapy sessions will generally involve building rapport withpatients, understanding patient thoughts and behaviours about heart failure,educating patients about depression and setting and reviewing assignments.

Measurements: Detailed assessment of heart failure symptoms, NYHA class, sixminutes walking distance, handgrip strength, height, weight, blood pressure, serumcreatinine, co-morbidities, medical management, quality of life, and sociodemographicvariables will be collected at baseline. The measurements will berepeated annually. Additionally, hospitalisation data and mortality data will becollected at regular intervals (once in three months or during every follow-up visit)during the follow-up period.

Statistical analyses: Intention to treat analyses will be performed. Cox-proportionalhazard model will be used for estimating the effectiveness of individual therapies andtheir cumulative effect on mortality. Generalised estimating equations will be used toestimate the effect of the interventions on other secondary outcomes.

Expected outcomes: The study will provide good quality, unbiased evidence on theeffectiveness of different components of the structured cardiac rehabilitationprogramme in reducing mortality and improving quality of life in heart failure patients.