Session 01 : Heart Failure

Session 1: Heart Failure
Chairpersons: Kewal Krishan and Arun Bandyopadhyay

5:05-5:25 Sandeep Seth 
5:25-5:45 Sagartirtha Sarkar 
5:45-6:05 Sujata Mohanty 
6:05-6:25 Debojyoti Chakraborty 

Epidemiology of Acute Heart Failure in India

posted Jan 25, 2017, 10:40 PM by sourav ghosh

Sandeep Seth
All India Institute of Medical Sciences , New Delhi, India

In a study done from AIIMS (The AFAR study) , the patients were relatively young (mean age 53 years), the causes were usually ischemic cardiomyopathy or idiopathic cardiomyopathy though RHD was also a contributor. Mortality was high though patients were receiving medications as per the HF guidelines though at lower doses.
The mean age (53 years) was lower than Western cohorts (ranging from 65 to 73 years) such as EuroHeart Failure (EURO-HF) Study, the Acute Decompensated Heart Failure National Registry (ADHERE), the Organized Program to Initiate Life-Saving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), and the Effects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure (EVEREST). This supports the concept that cardiovascular disease affects patients in India at a younger age than their Western counterparts. Overall, the mean ejection fraction was lower (29.2%) than ADHERE (34.4%) and OPTIMIZE-HF (39%).
The patients had high rates of in-hospital mortality (30.8%), 6-month mortality (26.3%) and 6-month re-hospitalization (39.5%). Data from ADHERE, OPTIMIZE-HF, EURO-HF demonstrate an overall in-hospital mortality rate of 4-7%, 90-day (limit of follow-up) mortality rate of 5-15%. 
Inpatient medication rates were different from rates in Western literature. Intravenous inotropes were used more commonly in our inpatient cohort (75%) compared to OPTIMIZE-HF data (5.4%). In-hospital mortality of the subset of patients who received inotrope therapy and had admission systolic BP <120 mmHg was 17.9% in OPTIMIZE-HF and 44.4% in our patient cohort, reflecting the severity of disease in this subgroup. Baseline mean renal function, which typically affects the clinical decision to begin inotrope therapy, appeared lower compared to OPTIMIZE-HF. Mean serum sodium, which is another prognostic marker for HF, was also lower compared to OPTIMIZE-HF (134.8 mmol/dl compared to 136.7 mmol/dl). 
Discharge medication rates of ACE-I/ARB (71.1%) were at or above levels seen in ADHERE and OPTIMIZE-HF. Despite similar diagnostic rates and adherence to performance measures as compared to Western literature, 6-months mortality and 6-months re-hospitalization rates in the patients were 26.3% and 39.5%, respectively, which may reflect the severity of illness presentation in this cohort.
This data and similar data from some small studies from other parts of India suggest that acute heart failure is a major problem in India which needs to be tackled on an urgent basis.

A step closer to unravel the mystery of myocyte self-regeneration during cardiac hypertrophy

posted Jan 25, 2017, 10:38 PM by sourav ghosh

Sagartirtha Sarkar
Professor, Genetics and Molecular Cardiology Laboratory, Department of Zoology, University of Calcutta, India

Cardiac hypertrophy leading to heart failure is one of the major causes of mortality worldwide that is triggered by nitrosative stress mediated apoptosis of terminally differentiated cardiomyocytes. S- nitrosylation of NEMO was studied in regulation of myocyte fate during cardiac hypertrophy. Myocyte targeted overexpression of S-nitrosyl mutants of NEMO in renal artery ligated rats showed significant downregulation of hypertrophy marker genes and betterment of cardiac function. S-nitrosyl mutants of NEMO showed downregulation of apoptotic potential of myocytes along with excess nuclear translocation of p65 protein within these cells during hypertrophy. Our lab earlier showed downregulation of p65 during regression of hypertrophy as a concomitant effect of reduced apoptotic load in cardiomyocytes. However, S-nitrosyl mutants of NEMO showed constitutive activation of p65 even when apoptotic load was lowered during regression of hypertrophy, thus inducing a subset of genes involved in cellular proliferation that shifted the balance towards regeneration of terminally differentiated cardiomyocytes and subsequent improvement in cardiac function. Thus, introducing S-nitrosyl mutants of NEMO in pathological cardiac microenvironment promises to be a potential tool for damaged tissue engineering via regeneration of quiescent myocyte population.

Use of stem cells for cardiovascular diseases: current status

posted Jan 25, 2017, 10:36 PM by sourav ghosh

Sujata Mohanty
Professor, Stem Cell Facility (DBT- Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi, India 

Cardiovascular diseases (CVDs) has become one of the leading causes of death worldwide. Despite several recent advancements in surgery and medicine, no treatment has come up as the fundamental care for cardiac disease modulation, yet. In this regard, regenerative medicine has endowed with new light to restore structural and electrophysiological function of the damaged heart in treatment of MI. Currently, the two different sources of stem cells are used in various applications in regenerative medicine; these are embryonic stem cells (ESCs) and adult stem cells (ASCs). ASCs are preferred over ESCs due to ethical acceptance, less/no risk of teratoma formation, easy isolation from different adult tissues and easier expansion in culture. ASCs have being tested in several clinical trials and have shown promising results. However, there is inconsistency in the results due to non-uniform isolation techniques, donor specificity and culture conditions adopted for expansion of ASCs. Currently, the focus of research is to find out most optimum source of ASCs along with its mode of transplantation so as to enhance its efficacy. Use of ASCs is being combined with tissue engineering, so as to avoid the issues of loss of stem cells during direct injection. Various scaffolds have been tested in animal models of myocardial infarct and have shown better results. Along with this, other strategies currently under investigation which may contribute in the future to regenerative medicine include use of induced pluripotent stem cells (iPSCs)-derived cardiac progenitor cells, directly reprogrammed cardiomyocytes from and acellular therapies using cytokines and growth factors. 
In the talk, I shall be discussing about the achievements and current status of Stem Cell Research within and outside India in the cardiovascular diseases. Also, I shall be talking about the stumbling blocks at present in this research areas and the future prospects. 

Growing 3D hearts: A perspective on organoids for translational research

posted Jan 25, 2017, 10:34 PM by sourav ghosh

Debojyoti Chakraborty
CSIR-Institute of Genomics & Integrative Biology, New Delhi, India

The field of regenerative medicine has experienced a rapid boost since the development of mini organs in the lab, also known as organoids. These miniature organs have paved the way for studying models of development and establishment of platforms for personalized medicine. Growing cardiac organoids is a relatively new area of research and offers exciting avenues for modelling heart disorders. Current technologies allow organoid development from cells originating from the organ or from reprogrammed induced pluripotent stem cells (iPSCs), the latter being a powerful tool for personalized therapies. Combining bioengineering techniques for providing optimal scaffolds to efficient methods of organoid development, scientists are currently striving to utilise organoids for solving complex disease pathways and modelling developmental programmes.

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