ICMR CENTRE FOR ADVANCED RESEARCH AND EXCELLENCE IN HEART FAILURE The activities of the proposed CARE in HF at the Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) will be a model for future research initiatives in India. BIO-SKETCH OF PI Dr. S Harikrishnan is currently Professor of Cardiology at the Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, Kerala. A post-doctoral from SCTIMST, Dr. Harikrishnan had a Commonwealth Fellowship in Leeds University, UK. He has been very active in clinical and epidemiology research. He has more than 100 publications in international peer reviewed journals with more than 3500 citations and an h-index of 21. He was instrumental in setting up the largest pulmonary hypertension registry in India – PROKERALA and the largest heart failure (HF) registry – Kerala HF registry. He is also the regional co-ordinator of the MACE registry of ICMR. He currently holds research grants from the Wellcome Trust, ICMR and NHLBI. He is also formally trained in Public Health Leadership in Emory University, USA. Dr Harikrishnan's main interest is in heart failure and pulmonary hypertension. He has developed the first HF registry in the country with funding from ICMR – the Trivandrum HF Registry; the results were presented in the late breaking research session of the European Society of HF meeting in 2015. He then converted the registry into a cohort, which is the first such cohort in India, now the follow-up is into the fifth year. The 90 day, one year and 3 year follow-up of the patients with HF has been published in high impact journals. Dr Harikrishnan's research collaboration under ICMR – the National Heart Failure Registry CO-INVESTIGATORS Dr G Sanjay (Additional Professor of cardiology) at the Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, Kerala. A Post Doctoral Fellowship (Adult Cardiology & Interventions) from SCTIMST has been very active in Coronary Artery Disease - Epidemiology and Prevention , Adult Cardiovascular Interventions and Cardiovascular hemodynamics Dr Jeemon Panniyammakal PhD, MPH is currently Assistant Professor at Achutha Menon Centre for Health Science Studies - Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, Kerala. Dr. Jeemon Panniyammakal received his PhD from the University of Glasgow, UK. He received his MPH from the Sree Chitra Tirunal Institute of Medical Sciences and Technology in Kerala, India. Dr. Jeemon Panniyammakal is a 'trained epidemiologist' with over a decade of experience in observational epidemiological studies and clinical trials. He has developed a focus on cardiovascular disease epidemiology and participated in several landmark epidemiologic studies and clinical trials in India. TEAM MEMBERS Linda Koshy is Scientist-B with the CARE-HF Project, and manages the Heart Failure Biobank and the NGS project on Hypertrophic Cardiomyopathy in Indian patients. Trained in Biotechnology (MSc. CUSAT, 2002; PhD. RGCB, 2009; Postdoc at Yamaguchi University Japan, 2012), her research has focused on the genetic epidemiology of complex diseases, pharmacogenomics, microRNA biology and cancer stem-cell markers. She has secured research funding as PI from the Department of Science and Technology, Govt. of India, and the Kerala State Council for Science, Technology Environment, and has published in peer-reviewed journals. Dr. Reethu S, (BDS, MPH) is currently working as Scientist B in Centre for advanced research and excellence in Heart failure (CARE HF) project funded by ICMR at SCTIMST. She has 8 years of experience in academics and research. Her area of expertise is tool development and validation and observational study. Madhuma. M Currently working as Project Technician in Heart failure Biobank and NGS on Hypertrophic cardiomyopathy. She received Masters degree in Biotechnology from MG University, Kottayam. Also received PG Diploma in Molecular Diagnostics from Inter University Centre for Genomics and Gene Technology, Kariavattom Campus, Kerala University. She has experience in Molecular Techniques, cell culture and has got training from RGCB and RCC. Divya Prasad is currently working as Project Assistant in Centre for Advanced Research & Excellence in Heart Failure (CARE HF) at Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, Kerala. She completed her Graduation in Nursing from Kerala University. Also completed Diploma in Neuro Nursing from SCTIMST, Trivandrum . She has five years of both clinical & research field experience. Shamla. S is currently working as Junior Nurse in centre for advanced research and Excellence in Heart failure (care HF) at Sreechitra tirunal institute for medical Science and Technology (SCTIMST), Trivandrum, Kerala. She completed her graduation in nursing from Dr. N.T.R University of health sciences in Vijayawada, Andhra pradesh. She has 3 years of teaching experience and had worked as Staff Nurse in Cardiac Surgery Department of SCTIMST BACKGROUND OF THE PROPOSAL Contemporary data from India are sparse regarding burden of heart failure (HF). However, the global burden of disease study estimates that deaths due to hypertensive heart diseases (mainly HF) increased by 138% from 1990 to 2013. Current estimates of prevalence of HF based on modelling studies indicate that the number of individuals with HF in India is as high as 23 million. Our study conducted in the state of Kerala, suggests that the incidence of HF is around 1 per 1000 population. Our data also shows that only 20% of patients in our country receives guideline-based medical treatment and those who are not getting ideal treatment experiences high mortality. The 3 year mortality of 45% in our Trivandrum cohort is one of the highest reported so far. (Harikrishnan S et al. Am Heart J. 2017 Jul;189:193-199; European Journal of Heart Failure (2015) 17, 794–800; J Card Fail 2018) WHY SCTIMST? SCTIMST has three wings – Hospital wing, Biomedical technology wing and Public health Institute. The amalgamation of these three will be an ideal combination to have the Center of Excellence (COE) in heart failure. We can have clinical studies, epidemiological studies and also device development as components of the COE. We have played the lead role in establishing major cardiovascular registries and research collaborations in the region and at the national level. We already have an established HF unit which includes a heart failure clinic with over 1000 patients enrolled. We also have recently commissioned a Heart Transplant unit with support from TATA Trusts. All the infrastructure for carrying out the proposed research activities are already established or is easily accessible. PROPOSED RESEARCH ACTIVITIES RESEARCH ACTIVITY 1: To harmonise the exiting HF registries in the region and develop a common HF database of over 10,000 heart failure patients in India. We have access to heart failure registries of over 10,000 patients currently. The immediate objective is to harmonise the database and collect the long-term follow-up of these patients. Analyses of baseline demographic and clinical characteristics and their relationship with long-term outcomes will help us to identify high-risk sub-groups of patients who may benefit from intensive lifestyle and pharmacological therapies. Identifying the practice patterns and their relationship with long-term outcomes will help us to understand gaps in implementation of evidence based treatments and further develop a quality improvement programme. RESEARCH ACTIVITY 2: To establish a Biobank of HF patients to study genetic, metabolomics and proteomic markers of health outcomes in heart failure patients. The biobank will aid in developing future research portfolios in heart failure genetics and omics research. RESEARCH ACTIVITY 3: To study the Micro-economic and psychosocial impact (including quality of life -QOL) of heart failure on individuals and families. We will conduct detailed micro-economic assessment to understand financing mechanism for heart failure care, and resulting distress financing and catastrophic health expenditures. Additionally, we will also study psychosocial co-morbidities in heart failure patients and their likely impact on their QOL. We will also develop and test a brief psychological counselling tool (2-3 sessions of in-person counselling) for improvement of QOL. We will use a randomized controlled trial to test the effectiveness of the brief psychological counselling session in improving the quality of life and treatment adherence. RESEARCH ACTIVITY 4: To assess the potential of a Quality improvement initiative of task sharing and mHealth (mobile phone based) interventions by trained nurses and family care givers in improving the practice of evidence based care for management of HF in India. We propose a cluster randomized controlled trial in 12 centres in Kerala to evaluate the effectiveness of the quality improvement strategy. RESEARCH ACTIVITY 5: To develop point-of-care (POC) BNP and INR machines and a computer algorithm for management based on BNP and INR values in primary and secondary care settings. The POC devices will be developed with the help of biomedical technology wing of SCTIMST. We have been already working on development of an algorithm for managing anticoagulation therapy based on INR values with the help of machine learning techniques. TRANSLATIONAL OUTCOMES Knowledge generated from this study has the potential to significantly affect new programmatic policy and clinical guidelines that will lead to improvements in HF management in India and other low and middle-income countries. Our research activities will also aim to address the cost-effectiveness of implementing the quality improvement initiatives like task sharing and mHealth interventions by trained nurses and family care givers. The development of POC devices, mHealth initiatives and Nurse based management will help to address the accessibility and affordability issues. Identification of high risk sub-groups among heart failure patients will help to target them for intensive lifestyle and pharmacological management. OVERALL BUDGET The proposed budget was about 4.9 crores.