|Year : 2018 | Volume
| Issue : 3 | Page : 171-176
Cardiovascular research convergence 2018
Soumi Das1, PD Subeen1, Shivani Vashista1, Karishma Landge1, Priya Raghav1, Nisha Laila1, Santoshi Kumari1, Dainy Thomas2, Nisha Thomas2
1 Department of Cardiology, AIIMS, New Delhi, India
2 Department of Nursing, Cardio Thorasic Center, AIIMS, New Delhi, India
|Date of Web Publication||11-Jan-2019|
Dr. Soumi Das
Department of Cardiology, AIIMS, New Delhi
Source of Support: None, Conflict of Interest: None
The Cardiovascular Research Convergence 2018 was held at International Centre for Genetic Engineering and Biotechnology and All India Institute of Medical Sciences on October 13 and 14, 2018. The program highlights were interactive sessions between clinical and basic scientists and case-based learning on cases of Eisenmenger syndrome, familial heart failure, and young patients with myocardial infarction. Some of the best research presentations included papers on vitamin deficiency in rats, cytochrome b5 reductase 3 as target to counter hypertension, high throughput screening for molecules for antihypertensive compounds in plants, Dhadkan: A smartphone app for heart failure (HF) patients, genetic variants in association with coronary artery disease in India, biomarkers after mitral interventions, the Indian experience with angiotensin receptor neprilysin inhibitor, and the AIIMS yoga program Kardiac Rehabilitation Yoga Trial in patients with HF. A program for training nurses in HF management was also conducted.
Keywords: All India Institute of Medical Sciences, angiotensin receptor neprilysin inhibitor, Cardiovascular Research Convergence 2018, high throughput screening, India, International Centre for Genetic Engineering and Biotechnology, nurses heart failure training, research, yoga
|How to cite this article:|
Das S, Subeen P D, Vashista S, Landge K, Raghav P, Laila N, Kumari S, Thomas D, Thomas N. Cardiovascular research convergence 2018. J Pract Cardiovasc Sci 2018;4:171-6
|How to cite this URL:|
Das S, Subeen P D, Vashista S, Landge K, Raghav P, Laila N, Kumari S, Thomas D, Thomas N. Cardiovascular research convergence 2018. J Pract Cardiovasc Sci [serial online] 2018 [cited 2019 Aug 23];4:171-6. Available from: http://www.j-pcs.org/text.asp?2018/4/3/171/249950
| Introduction|| |
The Cardiovascular Research Convergence 2018 was held at International Centre for Genetic Engineering and Biotechnology (ICGEB) and All India Institute of Medical Science (AIIMS) on October 13 and 14, 2018.
The main research areas at ICGEB focus on virology, immunology, development of diagnostics and vaccine candidates, structural biology (development of synthetic antibiotics and crystal structure determination of proteins and polypeptides), and in the field of malaria as well as development of technologies for biopharmaceuticals and for diagnosis of infectious diseases.
AIIMS provides specialty and super-specialty tertiary care services in >50 areas: anesthesiology, anatomy, antiretroviral treatment for HIV and AIDS, biochemistry, biomedical engineering, biophysics, biostatistics, biotechnology, cardiology for cardiac and heart-related treatments, community medicine, conservative dentistry and endodontics, dermatology and venereology, dietetics, endocrinology, metabolism and diabetes, forensic medicine and toxicology, geriatric medicine, and many others.
A program for training nurses in HF management was also conducted in parallel to the program.
The program highlights were interactive sessions between clinical and basic scientists and case-based learning. Some of the best abstracts for oral presentations are given in this issue.
| Basic Science Abstract|| |
1. Vitamin D Deficiency in Rats Mimics High-Fat High-Fructose Diet-Induced Cardiac Dysfunction
Hina L. Nizami, Parmeshwar B. Katare, Pankaj Prabhakar1, Sudheer K. Arava2, Praloy Chakraborty3, Subir K. Maulik1, Sanjay K. Banerjee
Drug Discovery Research Center, Translational Health Science and Technology Institute, Faridabad, Haryana, Departments of1 Pathology and2 Pharmacology, AIIMS,3 Department of Cardiology, VMMC and Safdarjung Hospital, New Delhi, India
Background: A large number cross-sectional study notwithstanding, a causal link between Vitamin D deficiency and the cardiac complications of metabolic syndrome, remains elusive. Our study aimed to investigate the role of Vitamin D deficiency as an independent risk factor for metabolic syndrome and resulting in cardiac outcomes, by studying Vitamin D-deficient diet- induced abnormalities, and to compare them with high-fat high-fructose fed model. Methods: Male Sprague–Dawley (SD) rats were fed with either control (Con), Vitamin D-deficient (Con[−]), or high-fat high-fructose diet (HFHFrD) for 20 weeks. At the end of 20 weeks, intraperitoneal glucose tolerance test, blood pressure measurement, and two-dimensional echocardiography (ECG) were performed. Serum and heart tissue were collected for biochemical and molecular investigation. Cardiac morphology and fibrosis were assessed in histopathology. H9C2 cardiomyoblasts were used for Vitamin D receptor (VDR) knockdown, 2-NBDG uptake assay, and immunocytochemistry study. Results: Induction of cardiac hypertrophy and fetal gene program in the Con(−) group was confirmed by increased heart weight-to-tail length ratio and gene expression (atrial natriuretic polypeptide, beta- myosin heavy chain, alpha skeletal actin, and transforming growth factor-beta). Left ventricular dysfunction (fractional shortening and ejection fraction) was observed in ECG. Renin, increased pro-inflammatory marker gene expression, decreased endogenous antioxidants, increased ERK1/2 phosphorylation, and increased perivascular fibrosis were observed. Vitamin D-deficient diet induced insulin resistance, dyslipidemia, and hypertension in rats. Reduced p-Akt (Ser473) level was observed in heart tissue. VDR knockdown in cardiomyocytes significantly reduced insulin-induced glucose uptake, glucose transporter type 4 translocation, and Akt phosphorylation. Most of the changes in Con(−) group were comparable with HFHFrD group. Conclusion: Our results indicate that Vitamin D deficiency in SD rats induces a phenotype similar to metabolic syndrome, myocardial insulin resistance, and cardiac contractile dysfunction induced by high-fat high-fructose feeding.
2. Cytochrome b5 Reductase 3 as a Nonconventional Therapeutic Target to Counter Hypertension
Gaurav Kumar, Sanjay Kumar Dey, Suman Kundu
Department of Biochemistry, University of Delhi South Campus, New Delhi, India
Hypertension (HTN) is a serious medical condition worldwide. Although available therapeutics are effective against HTN, they are often associated with complications. Hence, to pursue alternate antihypertensive therapeutics, the present study investigated cytochrome b5 reductase 3 (hsCYB5R3) enzyme as a “nonconventional” target, since this enzyme regulates the bioavailability of nitric oxide, a vasodilator involved in governing vascular tone and hence HTN. Small molecules were virtually screened against the crystal structure of the enzyme to identify potential inhibitors. The inhibitors so obtained were tested in vitro to calculate inhibitory concentration 50 values of these compounds against hsCYB5R3. Fluorescence and circular dichroism spectroscopy were employed to obtain binding affinity, number of binding sites, and effect of the compounds on 2° structure, respectively. Potential binding and stoichiometric ratios for some of the inhibitors were observed, some of which were not hemolytic either. The encouraging findings have poised us to investigate the inhibitors further.
3. Screening of Compounds Exhibiting Antihypertensive Properties
Manisha Saini, Sanjay Kumar Dey, Pankaj Prabhakar, Suman Kundu
Department of Biochemistry, University of Delhi South Campus, New Delhi, India
With the escalation in deaths by hypertension (HTN), novel drugs with lesser side effects are required; hence, healing by naturopathy is indispensable. The aim is to uncover the bioactive components in plant extracts against peripheral dopamine beta-hydroxylase (DBH) which is a pivotal enzyme involved in the conversion of dopamine to norepinephrine, which leads to vasoconstriction and causes HTN or cardiac hypertrophy. High throughput screening was applied to speed up the search of a novel inhibitor. Diverse natural compound libraries from available databases were docked against the active site of DBH. In addition, various plant extracts were assessed via colorimetric assay against DBH. The ones which exhibited higher or equivalent inhibitory constant as compared to the known inhibitors such as nepicastat and disulfiram were taken forward. Furthermore, reversed-phase high-performance liquid chromatography-based assay was performed to determine the IC50. To validate the binding of leads and the enzyme, spectroscopic techniques such as fluorescence and circular dichroism were used. Fluorescence measurements were used to determine the KD and number of binding sites in the enzyme. Then, ex vivo (human embryonic kidney 293 cell lines) experiments were done to investigate hemolytic as well as cytotoxic features, if any, brought about by the inhibitor. In the near future, we aspire to check the lead candidates in vivo most likely in spontaneously hypertensive rats model to evaluate their therapeutic efficacies. Heart, kidney, liver, and lung tissues of the rats will also be examined to evaluate the dose-dependent repercussions on these organs.
| Clinical Abstract|| |
4. Dhadkan: A Mobile App for Remotely Monitoring and Providing Medical Assistance to Heart Failure Patients
Somesh Chaturvedi, Shreya Srivastava, L. Gopichandran1, Sandeep Seth2, Deepak Sharma
Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand,1 College of Nursing, All India Institute of Medical Sciences,2 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
Heart failure (HF) is a leading cause of mortality in the world. We have developed Dhadkan a mobile app (version 2) for remotely monitoring and providing medical assistance to the patients of HF. It collects patient data (at any desired interval) on blood pressure, heart rate, and weight, and transmits it to the authorized caregiver (a doctor, nurse, or paramedic) who is linked to the patient during the initial registration. It also provides two- way communication between doctors and patients. In addition, patients can send images of any reports (for example, electrocardiography or echo) to the doctor. Patients also have the freedom to change his/her doctor. On doing so, the entire medical history of the patient is transferred to the new doctor. Most importantly, it automatically sends a notification to both the doctor and the patient, in case(s) of any drastic changes in patient's data, indicating a possibility ofimminent HF. Thus, it not only eliminates the need for manual monitoring of each patient by the doctor but also helps them in proactively recommending precautionary action during the treatment period. Dhadkan mobile app will help in saving the precious lives of HF patients. In addition, it will be of tremendous benefit to those who do not have any tertiary care hospitals near their homes. The app has been developed and designed in such a way that it can be easily used by rural people as well. Dhadkan app is freely available on Google Play Store for the use of doctors and patients (https://play.google.com/store/apps/details?id = com.compbio.iitr.dhadkan).
5. To Identify Genetic Variants in Association with Coronary Artery Disease with Respect to Indian Population
Salwa Naushin, Subhoshree Ghose, Sandeep Seth, Shantanu Sengupta
Institute: CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
Background: Complex diseases such as coronary artery disease (CAD) are controlled by various genetic, environmental, and lifestyle factors. A number of genetic polymorphism has been associated with CAD in different population by genome-wide association studies. However, considering the genetic susceptibility and unique lifestyle of Indians, genetic association of polymorphism with CAD in context of Indian population has not been very well established. Here, genotyping of single-nucleotide polymorphisms (SNPs) among CAD patients and controls was done with the aim to identify the genetic variants associated with CAD in Indian population. Methods: DNA was isolated from 576 subjects of which 274 were CAD patients and 302 were controls. Using the isolated DNA genotyping was done with Illumina Infinium Global Screening Array-24 v1.0. The genotyping data obtained were checked for quality through PLINK1.9. Individuals were filtered on the basis of genotyping call rate, sex discordance, heterozygosity rate, cryptic relatedness, and population structure. Similarly, genomic variants were filtered on the basis of missing rate, minor allele frequency, and Hardy–Weinberg equilibrium. Association test was done from the filtered data to obtain variants associated with disease phenotype. Results: We were able to identify 189 SNPs with P ≤ 0.0005. SNP rs9436640 lies in NFIA gene is found to be associated with CAD phenotype. This allele has already been reported to be associated with QRS duration and cardiac ventricular conduction (Nona et al., 2010). rs2207790 and rs2207791 SNP are the novel variants in NFIA which are found to be associated in our study. rs3924457 mapping to intron of TRPC6 also gave association signal. We also found SNP rs73398519 in IL33 gene to be associated with disease phenotype. Conclusions: The location of rs9436640 and rs73398519 in NFIA and IL33 gene, respectively, supports its potential involvement in the pathogenesis of CAD. This might further help in understanding the disease mechanism.
6. Study of Change in Brain Natriuretic Peptide Levels in Patients Undergoing Percutaneous Balloon Mitral Valvotomy
Ankesh Kumar, H. S. Isser, Preeti Gupta, Praloy Chakraborty, Ankit Jain, Mahendra, Ankit Singh, Sandeep Bansal
Department of Cardiology, Safdarjung Hospital and VMMC, New Delhi, India
Background: Brain natriuretic peptide (BNP) levels are shown to correlate positively with the severity of the stenosis in patients with rheumatic heart disease. Since changes in biomarker levels in the left atrium precede serum changes, it is postulated that left atrium sampling could provide an early indication for the success of the procedure and could offer immediate guidance for predicting favorable results. To address these lacunae, we planned this study to evaluate the BNP levels in patients undergoing balloon mitral valvotomy and examine the correlation with hemodynamic outcomes of balloon mitral valvotomy. Materials and Methods: The study population consisted of 50 patients with rheumatic mitral stenosis who underwent percutaneous transvenous mitral commissurotomy. BNP levels in the peripheral and left atrium blood of these patients were measured before percutaneous transvenous mitral commissurotomy and after 20 min of the procedure. BNP levels were also measured from peripheral blood at 48 h and at 1 month. These levels were then correlated with various echocardiographic and hemodynamic parameters measured before and after percutaneous transvenous mitral commissurotomy, at 48 h and at 1 month. Results: Seventy-four percent of the study population was females and the most common presenting symptom was dyspnea which was present in 90% of the patients. All patients who underwent successful percutaneous transvenous mitral commissurotomy showed a significant decrease in the left atrium BNP levels (415.57–362.21 pg/ml, P = 0.003) and peripheral BNP levels at 20 min (decreased from a mean 410.18 pg/ml to 336.45 pg/ml, P < 0.001) and peripheral BNP at 48 h (336.45–202.60 pg/ml, P < 0.001) and left atrium BNP levels at 1 month (410.18–102.66 pg/ml, P < 0.001) along with a significant improvement in mitral valve area (0.83–1.52 cm2, P < 0.001), left atrium area (25.95–21.97 cm2, P < 0.001), right ventricular TAPSE (17.49–20.97, P < 0.001), left atrium pressure (28.60–13.14 mmHg, P < 0.001), mean pulmonary artery pressure (43.88–26.46 mmHg, P < 0.001), and other echocardiographic and hemodynamic parameters (P < 0.001). Conclusions: The decrease in BNP levels following percutaneous transvenous mitral commissurotomy reflects a significant improvement in clinical and hemodynamic status; hence, it is reasonable to suggest that BNP is helpful in evaluating the clinical and hemodynamic outcome of percutaneous transvenous mitral commissurotomy.
7. Dental Implant Considerations in Patients Undergoing Anticoagulation Therapy: a Literature Review
Department of Prosthodontics and Crown and Bridge, Army Dental Centre Research and Referral, Army Hospital Research and Referral, Delhi Cantt, India
Introduction: Despite improvements in diagnosis, treatment and therapeutic techniques, CardioVascular Diseases (CVDs) are still a leading cause of death in most developing countries. Anticoagulation therapy involving use of drugs like Warfarin, Heparin, Clopidogrel or Aspirin is one of the most prevalent form of treatment used in CVDs. These drugs reduces the thromboembolic risk related to cardiovascular disease but may increase the bleeding risks related to any surgery. Many CVD patients seek prosthodontic rehabilitation for partial or complete edentulism. With advancements in field of implantology and implant related surgical procedures, dental implants are thefirst choice of treatment. An interdisciplinary approach involving dentist, cardiologist and pathologist is important for a successful implant therapy. Purpose: To review contemporary oral anticoagulation therapy and formulate literature based recommendations on the perioperative management of patients undergoing anticoagulation therapy in practice of implant dentistry. Discussion: Multiple protocols have been recommended for surgical placement of dental implants in patients undergoing anticoagulant therapy. Most important consideration is INR (International Normalized ratio) values which govern the choice of protocol that includes suspending oral anticoagulant therapy several days prior or altering oral anticoagulant therapy with heparin or reducing dose of anticoagulant or no change in the oral anticoagulant drug regimen. Similarly different approaches to surgical procedure have been suggested including a flap surgery or flapless surgery with use surgical stents for implant placement. Also use of locally applied hemostatic agents intraoperatively and post operatively is also highly debatable. Continuous monitoring of INR values, multidisciplinary discussion and situation based protocol for perioperative management forms an essential determinant of success in dental implant placement for patients undergoing anticoagulant therapy.
8. Trends in Heart Failure Management Study
Shivani Vashista, Sandeep Seth, For the AIIMS Heart Failure Team
Department of Cardiology, AIIMS, New Delhi, India E-mail: firstname.lastname@example.org
Background: The current guidelines recommend the use of vasodilators, beta-blockers, mineralocorticoid receptor antagonists in all patients of heart failure (HF). Data from India suggests that only 25%–50% of the patients get the recommended medications. The study question for the trends in HF management (THF) study is to study: “What are the patterns and factors associated with use and dose of HF with reduced ejection fraction (HFrEF) medications in current practice?” In this report, we analyze the use of one of the newer vasodilators: Sacubritil and valsartan, in patients of heart failure. Sacubritil and valsartan is a combination drug described as a new class of dual-acting angiotensin receptor–neprilysin inhibitor (ARNi). Results: A total of 125 patients with signs and symptoms of HF aged 15–74 years were started on ARNi. The study cohort consisted of 63% males, with an ejection fraction ranging from 15% to 40%; >80% had been on a previous angiotensin-converting enzyme (ACE) inhibitor and the remaining had been on a previous angiotensin receptor blocker (ARB). No patient was started de novo. All patients were switched to ARNi because they were still symptomatic in spite of being on maximum tolerated doses of ACE/ARB. The patients were followed up weekly for the 1st month and then 3 monthly. The follow-up range is from 1 week to 1 year. At follow up 69% showed improvement by at least one New York Heart Association (NYHA) class and this improvement started showing up between 1 week and 4 weeks. The doses per day ranged from (still being titrated up): 25–50 mg (42%), 100–150 mg (43%), and >150 mg (15%). There was no change in NYHA class in 18% at the time of follow up and in 12% there was either worsening or drug withdrawal due to hypotension or other side effects or had to be stopped due to the cost of the drug. Conclusions: In this preliminary analysis of the THF study, we found that the new vasodilator sacubitril–valsartan is safe to use in Indian patients, shows a benefit within a month, and needs to be started in very low doses and titrated slowly. Indian patients might tolerate lower doses, but more data are required on dosing [Figure 1].
9. LCZ 696: Experience at a Tertiary Center
Jeetesh Jain, Preeti Gupta
Department of Cardiology, Safdarjung Hospital and VMMC, New Delhi, India
Background: Sacubitril/valsartan combination (LCZ696) has been included as a Class IB recommendation by the 2016 ESC and ACC/AHA/HFSA guidelines for heart failure with reduced ejection fraction (HFrEF) with NYHA Class II through IV HF. A study was conducted to see the effect of the angiotensin receptor–neprilysin inhibitor LCZ696 in patients who had HFrEF. Methods: In this study, we assigned patients with Class II, III, or IV HF and an ejection fraction of 40% or less to receive LCZ696 (at a dose of 100 mg twice daily), in addition to recommended the guideline-directed medical therapy. The primary outcome was improvement in ejection fraction and dyspnea. Death from cardiovascular causes or hospitalization for HF was also studied. Results: A total of 54 patients received the drug. Out of these, 42 were males and 12 were females. The average age of the patients was 64 years. The trial was done for 6 months. Two patients dropped out of the study due to financial constraints and two patients (3%) stopped drug due to serious side effects. The mean improvement in ejection fraction was 5% ± 2%. The improvement in left ventricular ejection fraction was noticed in 20 patients (38%). Majority of patients (22; 37%) enrolled had dyspnea of grade NYHA Class II at the start of the study. Nine patients (17%) had an improvement of dyspnea of at least one grade. Four patients (7%) receiving LCZ696 died due to cardiovascular cause. Two patients (3%) were hospitalized for HF. Conclusions: LCZ696 improves left ventricular ejection fraction of the patients. LCZ696 improves the dyspnea of the patient.
10. The Effect of Lifestyle Management through Indian System of Medicine Including Ayurveda and Yoga on Overall Health Status among Heart Failure Patients: An Ongoing Kardiac Rehabilitation Yoga Trial
Karishma Landge, Archana Saini, Priya Raghav, Sandeep Seth
Department of Cardiology, AIIMS, New Delhi, India
Background: Heart failure (HF) ranks among the top chronic illnesses with a profound clinical and economic impact. Symptoms of HF including reductions in physical function, increased dyspnea, and fatigue significantly reduce quality of life (QOL). Although medications have improved both symptoms and mortality, side effects and substantial risks plague the consistent use of these medications. Little is known about the effects of yoga on physical and psychological function in HF patients. The purpose of this study is to determine whether a 12-week yoga program is safe and would positively influence physical and psychological function in HF patients. However, a 1-year extended follow-up will be done for the subjects to evaluate the major adverse cardiac and cerebrovascular events. Methods: In the current ongoing prospective trial, moderately sick patients (NYHA I–II) HF patients have been recruited from the HF Clinic of AIIMS, New Delhi, and randomized to either intervention or control arm. Both the groups followed the standard care whereas yoga arm got additional Ayurvedic lifestyle, diet counseling, and yoga sessions over 3 months. Echocardiographic parameters, 6-min walk (6MW) test, and Kansas City cardiomyopathy questionnaire (KCCQ) were assessed at baseline and after 3 months. Results: Preliminary analysis of thefirst few patients in this ongoing study shows significantly improved 6MW distance (71.5 ± 29.55 m vs. 75 ± 70.71 m) and ejection fraction (EF) (2.84% ±5.80% vs. 8.6 ± 5.65%). The intervention arm also had improvement in QOL and reduced symptom frequency that led to greater improvement in the KCCQ overall summary score. Conclusion: Yoga improved exercise capacity and EF in patients with HF, and there was also a trend toward improvements in all parameters of KCCQ. This is an ongoing study and the initial results are promising [Figure 2].
|Figure 2: Six-minute walk test and Kansas City cardiomyopathy questionnaire.|
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The main conference was held over 2 days [Figure 3] at ICGEB and AIIMS and the nurses training program was held at AIIMS [Figure 4].
The workshop for nurses on heart failure management [Figure 4] was organized by Heart Failure Services, CNC, AIIMS, in association with Nursing In-service Education (NIE), CTC, AIIMS. Workshop was held on October 14, Sunday. The venue of the workshop was Lecture Theatre-1. A total of 57 delegates were present for the conference. The topics for the discussion were (1) heart failure basics, (2) The medical management of heart failure, (3) investigations in heart failure, (4) device therapy in heart failure, (5) case studies in heart failure, Part 1 basics, (6) diet in heart failure, (7) pretransplant workup and surgical techniques of heart transplant, (8) postheart transplant patient management, (9) heart failure nurses and heart failure clinics, (10) heart failure rehabilitation, (11) case studies, Part 2: advanced heart failure. At the end of the workshop feedbacks were assessed. In overall assessment of the event, 70% of the delegates assessed it as good, whereas 26% assessed it as excellent, and 4% assessed it as average. In Assessment of the level of sessions at which objectives of the workshop achieved, 83% of delegates assessed it as good whereas 17% assessed it as excellent. In applicability of the knowledge gained during the workshop in your clinical area, 81.5% of delegates assessed it as good and 18.5% assessed it as excellent. In assessment of the balance of theory and practice in the workshop, 89% of delegates assessed it as good and 11% assessed it as excellent. Time management of the workshop, 70% of delegates assessed as good, 12.6% assessed as excellent and 7.4% of delegates assessed as average. In the organization level of workshop in terms physical arrangements, 75% of delegates assessed as good, 15% assessed as excellent and 10% of delegates assessed s average. In the assessment of quality of presentation of the sessions, 50% of delegates assessed as good, 41% assessed as excellent and 9% of delegates assessed as average. Delegate's response to the program was positive and they requested programs with more skill sessions, with duration of 2 days in the future [Figure 5].
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]