Impact of COVID-19 on heart failure hospitalization and outcome in India - A cardiological society of India study (CSI-HF in COVID 19 times study - "The COVID C-HF study").

OBJECTIVES: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019. METHODS: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study. RESULTS: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days. CONCLUSION: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years.

COVID-19 infected ST-Elevation myocardial infarction in India (COSTA INDIA).

OBJECTIVE: To find out differences in the presentation, management and outcomes of COVID-19 infected STEMI patients compared to age and sex-matched non-infected STEMI patients treated during the same period. METHODS: This was a retrospective multicentre observational registry in which we collected data of COVID-19 positive STEMI patients from selected tertiary care hospitals across India. For every COVID-19 positive STEMI patient, two age and sex-matched COVID-19 negative STEMI patients were enrolled as control. The primary endpoint was a composite of in-hospital mortality, re-infarction, heart failure, and stroke. RESULTS: 410 COVID-19 positive STEMI cases were compared with 799 COVID-19 negative STEMI cases. The composite of death/reinfarction/stroke/heart failure was significantly higher among the COVID-19 positive STEMI patients compared with COVID-19 negative STEMI cases (27.1% vs 20.7% p value = 0.01); though mortality rate did not differ significantly (8.0% vs 5.8% p value = 0.13). Significantly lower proportion of COVID-19 positive STEMI patients received reperfusion treatment and primary PCI (60.7% vs 71.1% p value=< 0.001 and 15.4% vs 23.4% p value = 0.001 respectively). Rate of systematic early PCI (pharmaco-invasive treatment) was significantly lower in the COVID-19 positive group compared with COVID-19 negative group. There was no difference in the prevalence of high thrombus burden (14.5% and 12.0% p value = 0.55 among COVID-19 positive and negative patients respectively) CONCLUSIONS: In this large registry of STEMI patients, we did not find significant excess in in-hospital mortality among COVID-19 co-infected patients compared with non-infected patients despite lower rate of primary PCI and reperfusion treatment, though composite of in-hospital mortality, re-infarction, stroke and heart failure was higher.

Screening for Hypertension in Asymptomatic Individuals in India: An Expert Consensus Statement.

INTRODUCTION: Hypertension (HTN) is a rapidly growing epidemic in India. It is no larger restricted to older adults as more young Indians are being diagnosed with HTN. Despite its significant prevalence, the awareness, treatment, and control of HTN remain low in India. Thus, early diagnosis is essential to control HTN and prevent future complications. Screening for HTN can help identify undiagnosed and asymptomatic HTN, and thereby the early use of interventions to control the blood pressure (BP). However, no comprehensive guidelines have been established for effective HTN screening in asymptomatic individuals in an Indian setting. OBJECTIVE: To provide consensus recommendations for hypertension screening in India. CONSENSUS RECOMMENDATIONS: Screening for HTN can provide more effective control of HTN and reduce the complications. Experts recommended that the initial age at screening should be 18 years. In individuals at a high risk of HTN, targeted screening can be undertaken. BP measurement using an electronic BP recorder (with at least two readings) are required for identifying HTN during screening. In asymptomatic adults with BP <130/85 mmHg and BP of 130-139/85- 89 mmHg, rescreening should be conducted every 3-5 years and at least every year, respectively. Screening for HTN can be cost effective even when universal screening of the entire population is undertaken. CONCLUSION: The consensus recommendations would increase the awareness of HTN screening. Screening for HTN can provide more effective control of HTN and reduce the complications.

A multicentre retrospective study to understand anti-platelet treatment patterns and outcomes of acute coronary syndrome patients in India (TRACE).

BACKGROUND: There is limited available information for treatment of acute coronary syndrome (ACS) with respect to outcomes, therapeutic agents and treatment practices. Our retrospective registry study collected and evaluated varying anti-platelet treatment strategies and outcomes of ACS patients who were admitted to 9 different tertiary care hospitals in India. This study was carried out to provide an insight to anti-platelet treatment patterns and analyze outcomes of ACS patients in India. METHODS: All the relevant data, including anti-platelet treatment strategies, outcomes and patient treatment compliance were collected from 500 ACS (defined as STEMI, NSTEMI and unstable angina [UA]) cases from January 2007 to December 2009. These ACS cases were randomly collected from the hospital records and included in the analysis. The patient follow up data was acquired either from the hospital records or via telephonic contact for a period of one year following the event. RESULTS: Out of 500 ACS patients, 59.8% had UA/NSTEMI and 40.2% had STEMI. On hospital admission, aspirin, clopidogrel, statins, beta-blockers and angiotensin converting enzyme inhibitors (ACE-Is) were used by 83%, 83%, 68%, 43.2% and 31.6% patients, respectively. On discharge, aspirin, clopidogrel, statins and beta-blockers were used by 90.2%, 88%, 80.6%, and 59% patients, respectively. The average patient compliance to statins, clopidogrel and aspirin was recorded as 74.28%, 69.7% and 68.66%, respectively during discharge and follow-up visits. Greater than 50% of ACS patients after discharge were lost to follow-up and as a result there was significant drop in the number of clinical events reported. CONCLUSION: This pilot study conducted in tertiary care centers in India showed that patients with ACS were more often diagnosed with UA/NSTEMI as compared to STEMI and reported maximum compliance to statins, clopidogrel and aspirin after discharge over 1 year follow-up. More ACS patients were lost to follow up that resulted in low reporting of clinical outcomes, following discharge upto 1 year.

Cardiological Society of India practice guidelines for angiography in patients with renal dysfunction.

PREAMBLE: The potential risk of contrast-induced acute kidney injury (CI-AKI) has made utilization of coronary angiography in the work-up for the diagnosis of coronary artery disease in CKD quite low.(1) This is in contrast to increasing prevalence and severity of CAD as the serum creatinine rises.(2) In fact most CKD patients will succumb to CAD and not to ESRD.(3) Thus the judicious use of CAG/PCI in this setting is of prime importance but underused. The CSI began to develop guidelines for Indian context as most guidelines are those developed by ACC/AHA or ESC. The aim was to assist the physicians in selecting the best management strategy for an individual patient under his care based on an expert committee who would review the current data and write the guidelines with relevance to the Indian context. The guidelines were developed initially in June 2010 as an initiative of Delhi CSI. Three interventional cardiologist (SB, AS, KKS), one nephrologist (SCT) and two clinical cardiologists (ST, RG) along with Dr. Roxana Mehran (New York) and Dr. Peter McCullough (Missouri), U.S.A.; were involved in a three-way teleconference to discuss/debate the data. This was presented by SB, and over the next two hours each data subset was debated/agreed/deleted and this resulted in the "Guidelines for CAG in Renal Dysfunction Patients". These were then written and re- circulated to all for final comments. Further, these guidelines were updated and additional Task Force Members nominated by Central CSI were involved in the formation of the final CSI Guidelines. Both (Roxana Mehran and Peter McCullough) reviewed these updated Guidelines in October 2012 and after incorporating the views of all the Task Force members-the final format is as it is presented in this final document.

Safety and efficacy of indigenously developed and manufactured bivalirudin in moderate/high-risk Indian patients undergoing percutaneous coronary intervention: the Bivaflo Registry.

BACKGROUND: Current treatment strategies for percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) include concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and antithrombotic therapy such as aspirin, clopidogrel, and unfractionated or low-molecular-weight heparin. The "direct thrombin inhibitor" bivalirudin has been associated with better efficacy and safety than heparin. OBJECTIVE: The present study is performed to evaluate the safety and efficacy of an indigenously developed and manufactured bivalirudin (Bivaflo; Sun Pharmaceutical Industries Ltd., Mumbai) as the primary anticoagulation strategy during PCI in moderate-high risk patients with only provisional use of GPI. METHODS: This prospective multicentered registry enrolled 439 patients in 11 tertiary care centers across India. Patients who had ACS or other clinical/angiographic characteristics, which increase risk during PCI, were enrolled in the registry. Bivaflo was administered as a bolus dose of 0.75 mg/kg, followed by infusion at a rate of 1.75 mg/kg/h during the procedure and optionally 0.25 mg/kg/h for 4 hours after the procedure at investigator's discretion. GPI use was discouraged except as bailout. The primary endpoints were composite and individual incidences of death, myocardial infarction (MI), urgent revascularization, subacute stent thrombosis (SAT), or bleeding at day 7/hospital discharge, whichever was earlier. The secondary endpoints were 30-day composite and individual incidences of death, MI, urgent revascularization, and SAT. RESULTS: The mean age of the group was 58 +/- 10 years and 83% were males. Bivaflo was administered for a mean duration of 102 +/- 79 minutes, and 65% patients received Bivaflo infusion post-PCI. ACT values measured at 10 minutes after bolus and at the end of the PCI were found to be 339 +/- 110 and 336 +/- 104 seconds, respectively. GPI was provisionally used in only 4% (16) patients mostly due to new or suspected thrombus and obstructive dissection with decreased flow. At day 7/hospital discharge, there were no incidences of major adverse cardiac events or major bleeding. Minor bleeding occurred in only 4 patients (0.9%). The 30-day composite major adverse cardiac event rate was 0.68%. One death and two subacute thrombosis occurred during the 30-day follow-up. CONCLUSION: Bivaflo is safe and effective sole anticoagulation strategy during PCI of moderate-high risk patients. Bivaflo administration was associated with no major bleeding events and extremely low in hospital and 30-day MACE rate. These rates were lower than expected MACE rates for such a subgroup of patients based on historical controls.

WPW and preexcitation syndromes.

Wolff-Parkinson-White syndrome is a disorder characterized by presence of an accessory pathway which predisposes patients to tachyarrhythmias and sudden death. Among patients with WPW syndrome, atrioventricular reentrant tachycardia (AVRT) is the most common arrhythmia, accounting for 95% of re-entrant tachycardias. It has been estimated that one-third of patients with WPW syndrome have atrial fibrillation (AF). AF is a potentially life-threatening arrhythmia. If an accessory pathway has a short anterograde refractory period, then rapid repetitive conduction to the ventricles during AF can result in a rapid ventricular response with subsequent degeneration to ventricular fibrillation (VF). The accessory pathway may be located anywhere along the atrioventricular valve Most of the patients are young and do not have structural heart disease hence it is important to risk stratify these patients so as to prevent the sudden death. Management of asymptomatic patients with WPW syndrome has always remained controversial Catheter ablation of accessory pathways has become an established mode of therapy for symptomatic patients and asymptomatic patients employed in high-risk professions.

Contraction-mediated pinocytosis of RGD-peptide by dermal fibroblasts: inhibition of matrix attachment blocks contraction and disrupts microfilament organisation.

Force generation in collagen and matrix contraction are basic functions of fibroblasts and important elements of tissue repair. Cell-matrix attachment is critical to this contraction, involving RGD-binding integrins. We have investigated how this process operates, in terms of force generation (in the Culture Force Monitor) and cytoskeletal structure, using a synthetic RGD-decapeptide. The RGD-peptide blocked force generation over the first 6 h, followed by near complete recovery by 20 h. However, dose response was complex indicating multiple processes were operating. Analysis of cytoskeletal structure after treatment with RGD-peptide indicated major disruption with condensed aggregates of actin and microtubular fragmentation. Fluorescent labeling and tracking of the RGD-peptide demonstrated intracellular uptake into discrete cytoplasmic aggregates. Critically, these RGD-peptide pools co-localised with the condensed actin microfilament aggregates. It is concluded that RGD-peptide uptake was by a form of contraction-mediated pinocytosis, resulting from mechanical tension applied to the untethered RGD-peptide-integrin, as contractile microfilament were assembled. These findings emphasize the importance of sound mechanical attachment of ligand-occupied integrins (e.g., to extracellular matrix) for normal cytoskeletal function. Conversely, this aspect of unrestrained cytoskeletal contraction may have important pathogenic and therapeutic applications.

Single exposures to antiproliferatives: long-term effects on ocular fibroblast wound-healing behavior.

PURPOSE: To determine the long-term effects of single, 5-minute exposures to 5-fluorouracil (5FU) and mitomycin-C (MMC) on Tenon's capsule fibroblast migration, growth factor production, growth factor receptor expression, and extracellular matrix (ECM) production. METHODS: Monolayer cultures and the overlying growth medium of Tenon's capsule fibroblasts exposed to 5FU (0.25 to 25 mg/ml) or MMC (0.001 to 0.1 mg/ml) were harvested up to 48 days after treatment. The expression of growth factors and growth factor receptors, including transforming growth factor beta (TGFbeta), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF), and ECM molecules (collagen type I, collagen type III, and fibronectin) were quantitated at the mRNA and protein levels. The ability of fibroblasts exposed to 5FU and MMC to migrate to fetal calf serum was also investigated up to 48 days after treatment. RESULTS: Control cultures were found to produce the growth factors TGFbeta and bFGF but not EGF. Exposure to 5FU or MMC resulted in an initial significant increase (P < 0.05) in the production of TGFbeta and bFGF, with levels then decreasing toward those of controls. Cells exposed to 5FU or MMC exhibited an initial significant decrease (P < 0.05) in the number of TGFbeta, bFGF, and EGF growth factor receptors, with subsequent recovery toward control levels by day 48 after treatment. Both 5FU and MMC caused a significant reduction (P < 0.05) in collagen type I and fibronectin production compared to controls throughout the 48-day culture period. The production of collagen type III was initially elevated (P < 0.05) compared to controls after exposure to 5FU or MMC, production then decreasing toward control levels over the remainder of the 48-day culture period. The migration of cells exposed to 5FU or MMC was significantly reduced (P < 0.05) compared to controls up to 48 days after treatment; these cells exhibited a partial recovery of migratory ability throughout this period. CONCLUSIONS: Fibroblasts whose growth was arrested using single, short exposures to 5FU or MMC appear to be capable of performing several crucial aspects of wound healing, including the expression of growth factors and receptors and ECM molecules and the ability to migrate. These findings may help explain why in some patients treated with antiproliferatives, glaucoma filtration surgery fails because of scarring.

Coronary artery stenting for isolated proximal left anterior descending stenosis: immediate and follow-up results.

Between February 1995 to August 1997, 120 patients underwent elective stent implantation for isolated proximal left anterior descending coronary artery stenosis. Their age ranged from 31 to 72 years (mean: 50.8 +/- 10.2) and the majority (89%) were males. All patients had angina, documented myocardial ischemia or both and 70 percent or more luminal diameter stenosis in the proximal left anterior descending before the origin of any branch. Majority (62.5%) of the treated lesions were type A. Successful deployment of the stent at the target site was achieved in all patients without any major in-hospital complications, including myocardial infarction, emergency bypass graft surgery or death. Clinical follow-up, ranging from 6 to 31 months (mean: 18.5 +/- 8.1, median: 20), was available in 87 out of 92 (94.5%) eligible patients who had completed at least six months after the procedure. Freedom from angina, myocardial infarction, target lesion revascularization and death was observed in 90.8, 100, 95.4 and 97.7 percent of patients, respectively. By the Kaplan-Meier estimate, an event-free survival (absence of death, myocardial infarction, recurrence of angina or revascularization) was 95.4 percent at six months, 89.5 percent at 12 and 18 months and 82.7 percent at 24 to 31 months of follow-up. Only 10 (11.5%) patients developed any event and TLR was required in 4.6 percent of patients. In conclusion, elective stenting for isolated proximal left anterior descending stenosis can be achieved safely and successfully in all patients without any adverse in-hospital events. This modality of treatment also provides long-term benefits in terms of reduction in major cardiovascular events and need for subsequent revascularization.

Elective stenting for type B and C lesions: immediate results and follow-up angiographic restenosis.

From January to December 1995, 73 out of 174 patients with coronary artery disease underwent elective stenting for type B and C lesions. The age ranged from 35 to 73 years (mean +/- SD : 52.1 +/- 12.6) and the majority (91.7%) were males. Of the 74 vessels treated, the target vessel was LAD in 49 (66.4%), LCx in 13 (17.6%), RCA in 8 (10.8%) and SVG in 4 (5.2%). Based upon the ACC/AHA task force classification, 58 (79.5%) patients had type B1, 9 (12.3%) B2 and 6 (8.2%) had type C lesions. A total of 89 stents were deployed to treat 76 lesions with a range of 1 to 3 stents per lesion. A single stent was required for 67 lesions, 2 stents for 8 and 3 stents for 2 lesions. The stents used were Wiktor (29), Palmaz-Schatz (26), Gianturco-Roubin (24), Microstent (6) and Freedom (4), depending upon the anatomical and morphological characteristics with the lesion. Using high pressure strategy, the stents were deployed successfully in all (100%) with a reduction in luminal diameter stenosis from 92 +/- 5.4 to -5 +/- 6 percent. There was no subacute stent thrombosis despite nonusability of oral anticoagulation in 95.9 percent patients. None had any major complication in the form of acute myocardial infarction, need for emergency bypass graft surgery or death. Minor complications were encountered in 9 (12.3%) patients. At a mean follow-up of 26 +/- 14 weeks, 74 percent of the patients were asymptomatic. Out of 31 patients who had completed 6 months after the procedure, repeat angiography was performed in 29 (93.5%) at a mean duration of 29 +/- 6 weeks. The angiographic restenosis was found in 6 (20.7%) patients. In conclusion, type B and C lesions can be treated successfully using elective stenting with excellent immediate results and clinical outcome. Angiographic restenosis, which develops in about one-fifth of patients, appears to be much lower than reported after balloon angioplasty for these complex lesions.