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.

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.

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.

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.

Cytotoxicity mediated by soluble macrophage product(s).

The soluble macrophage product(s) released by nonimmune mouse peritoneal macrophages exposed to endotoxin or from listeria-immune macrophages after incubation with specific antigen mediated cytotoxic activity against malignant cell types and, to a lesser extent, against normal cells. Only undiluted supernatants from nonimmune or listeria-immune macrophages cultured with medium 199 alone exerted some degree of cytotoxicity on the different target cell types tested. The macrophage product(s) retained cytotoxic activity storage at minus 20 degrees C, was stable when heated at 56 degrees C for 30 minutes, but was completely inactivated when exposed at 100 degrees C for 5 minutes. In the presence of 15 mug exogenous lysozyme/ml, the cytotoxic activity of the macrophage product(s) was significantly enhanced.

Percutaneous transatrial mitral commissurotomy: immediate and intermediate results.

OBJECTIVES: The purpose of this study was to evaluate the immediate and follow-up results of percutaneous transatrial mitral commissurotomy in 600 patients with rheumatic mitral stenosis. BACKGROUND: Percutaneous transatrial mitral commissurotomy has emerged as an effective nonsurgical technique for patients with symptomatic mitral stenosis. Several studies have shown that the immediate results are comparable to closed and open mitral valvotomy. METHODS: Percutaneous transatrial mitral commissurotomy was performed in 600 patients with rheumatic mitral stenosis by the double-balloon (290 patients [48.3%]) and flow-guided Inoue balloon (310 patients [51.7%]) techniques. There were 154 male (25.6%) and 446 female (77.4%) patients with a mean [+/- SD] age of 27 +/- 8 years (range 8 to 60). Atrial fibrillation was present in 26 patients (4.3%), mitral regurgitation < or = grade 2 in 62 (10.3%) and densely calcific valve in 12 (2%). All patients had clinical and echocardiographic (two-dimensional, continuous wave Doppler, color flow imaging) follow-up at 3-month intervals. RESULTS: Percutaneous transatrial mitral commissurotomy was successful in 589 patients (98.1%), and optimal commissurotomy was achieved in 562 (93.6%), with an increase in mitral valve area from (mean +/- SD) 0.75 +/- 0.18 to 2.2 +/- 0.38 cm2 (p < 0.001) and a decrease in transmitral end-diastolic gradient from 27.3 +/- 6.1 to 3.8 +/- 4.2 mm Hg (p < 0.001). Mitral regurgitation developed or increased in 208 patients (34.6%). Six patients (1%) with mitral regurgitation required mitral valve replacement. Cardiac tamponade occurred in 8 patients (1.3%). Six patients (1%) died. Restenosis developed in 10 patients (1.7%) during a mean follow-up period of 37 +/- 8 months (range 6 to 66). CONCLUSIONS: Percutaneous transatrial mitral commissurotomy is an effective, safe procedure with gratifying intermediate results. It should be considered the treatment of choice for rheumatic mitral stenosis.

Maintenance of Fc receptors in hybrid cell lines obtained by fusing mouse splenic macrophages with mouse myeloma cells.

Mouse splenic macrophages were fused with cells of the mouse myeloma line P3-X63-Ag8 in the presence of inactivated Sendai virus. Two continuously growing hybrid cell lines were established from fusion mixtures. These hybrid cell lines exhibited macrophage-like morphology and continued to express macrophage derived Fc receptor activity even after prolonged culture in vitro.

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.

Elevated titers of cell-free interleukin-2 receptor in serum and cerebrospinal fluid specimens of patients with acquired immunodeficiency syndrome.

A sensitive monoclonal antibody based ELISA was used to detect cell-free interleukin-2 receptor (IL-2R) in the body fluids of patients with acquired immune deficiency syndrome (AIDS), a variety of other disease conditions and a control group of apparently healthy (heterosexual and homosexual) males. Two of the 25 control donors showed low titers (1:8) of IL-2 receptor in the serum samples; the cerebrospinal fluid (CSF) specimens from these individuals proved negative. However, serum and CSF specimens from all the 9 patients with AIDS showed significantly elevated titers (range 1:128 to 1:4096) of IL-2 receptor. The presence of moderate titers (range 1:128 to 1:512) of circulating IL-2 receptor could also be detected in all of the 4 patients with acute lymphocytic leukemia. IL-2 receptor was detectable in the CSF and/or serum specimens from 3 of 3 patients with lung cancer, 3 of 4 patients with acute hepatitis B infection, and 2 of 3 patients with multiple sclerosis. IL-2 receptor could not be detected in the serum or CSF specimens originating from patients with legionellosis (3/3), asthma (3/3), or those with non-pulmonary febrile bacterial infections (4/4). It is concluded that soluble IL-2 receptor may be found in serum or CSF specimens from patients with certain (but not all) disease conditions including AIDS. The conspicuously elevated titers of cell-free IL-2R in the body fluids of patients with AIDS may contribute to the drastic impairment of the immune system regulation observed in such patients.

Analysis of Ia-antigen(s) positive macrophages in experimental murine toxoplasmosis.

The present study has demonstrated marked increase in the relative percentage of Ia-positive macrophages among the peritoneal macrophage population(s) of BALB/c mice infected intraperitoneally with Toxoplasma gondii or when chronically infected mice were rechallenged with Toxoplasma. The observed increase in Ia-positive peritoneal macrophage numbers coincided with the appearance of interferon-gamma (IFN-gamma) in the sera of infected mice. The appearance of elevated serum IFN-gamma titer was a temporary event but the increased percentage of Ia-positive macrophages persisted. The data presented have documented that antigen-specific proliferation response of vigorously purified Toxoplasma-sensitized T-cells is dependent upon Ia-bearing macrophages. This model is useful for future studies into various aspects of the interaction(s) between parasite antigens and Ia-antigen(s) at the macrophage surface for successful recognition of antigen-specific T-cells.

Contribution of macrophage arginase in the intrinsic restriction of herpes simplex virus replication in permissive macrophage cultures induced by gamma-interferon containing products of activated spleen cells.

Cultured peritoneal macrophages (PM) from adult mice of strain DBA/2 (but not C57BL/6) supported productive replication of HSV, as monitored by infectious virus yield and electron microscopy. In contrast, PM of DBA/2 origin, when pretreated with supernatants of Con A-stimulated spleen cells containing immune interferon (IFN-gamma) activity, manifested remarkable intrinsic restriction to HSV replication. The acquisition of this intrinsic restriction to virus replication correlated with the generation of appreciably elevated levels of arginase in supernate of treated PM. Addition of incremental doses of exogenous arginine in the culture medium led to the abrogation of induced restriction to HSV replication in DBA/2 PM, indicating the critical role of arginase in the phenomenon. Furthermore, anti-HSV activity of arginase levels released into the culture medium of IFN containing supernate-treated PM became apparent when assayed on PM, which were precultured in arginine-deficient medium for 24 hours before virus infection and exposure to arginase containing preparation. Taken together, these observations indicate that macrophage arginase can mediate intrinsic restriction to HSV replication in PM.

Analysis of the roles of immune interferon (IFN-gamma) and colony-stimulating factor(s) in the induction of macrophage anti-toxoplasma activity.

Lymphokine-enriched, cell-free supernatants from specific antigen-stimulated spleen cells of toxoplasma-immune mice lacking detectable anti-toxoplasma antibody could generate effective anti-toxoplasma activity within normal (non-immune) murine peritoneal macrophages. Such supernatants also contained high levels of IFN-gamma as well as Ia-antigen(s) inducing activity. Supernatants from ConA stimulated normal (non-immune) spleen cells with high IFN-gamma, as well as CSF-containing supernatants from lung explants, lacked the capacity to induce anti-toxoplasma activity within peritoneal macrophages. ConA-stimulated spleen cell supernatants with high IFN-gamma titers but not CSF-enriched lung explant supernatants could induce the expression of macrophage cell surface Ia-antigen(s). Based on the results of our experiments, we have been able to eliminate the direct (by itself) role of IFN-gamma or CSF in generating macrophage anti-toxoplasma activity. However, the possibility that molecules like IFN-gamma or CSF synergize together with other immune spleen cell-derived factor(s) in the generation of effective macrophage anti-toxoplasma activity has not been ruled out.

Contribution of immune interferon (IFN-gamma) in lymphokine-induced anti-toxoplasma activity: studies with recombinant murine IFN-gamma.

Recombinant E. coli-derived murine interferon gamma (cDNA IFN-gamma) per se induced resident mouse peritoneal macrophages (MPM) and mouse embryo cells to exert marked antitoxoplasma activity. This capacity of cDNA IFN-gamma was abrogated by a specific antiserum to cDNA IFN-gamma which could only neutralize the antiviral activity mediated by this product, whereas a rabbit antiserum directed against murine IFN-alpha/beta proved ineffective in neutralizing these functions. It has been found that rabbit antiserum to cDNA IFN-gamma could also neutralize IFN-gamma-mediated antiviral activity present in crude lymphokine-enriched supernatants of antigen-stimulated toxoplasma-sensitized spleen cells (Toxo-LK) but proved ineffective in abolishing the capacity of Toxo-LK to trigger macrophage anti-toxoplasma activity. The data obtained suggest that macrophage anti-toxoplasma activity induced by Toxo-LK may be an interplay of multiple factor(s) and that Toxo-LK preparations contain soluble factor(s) other than IFN-gamma, which can induce macrophages to kill intracellular Toxoplasma. Experiments in which crude Toxo-LK preparations were incubated with lectin concanavalin A (Con A) showed that this treatment resulted in a block of anti-toxoplasma arming factor(s) activity, as well as a significant reduction of IFN-gamma-mediated antiviral activity present in Toxo-LK. By contrast, no significant difference was observed in the macrophage anti-toxoplasma activity mediated by Con A or untreated cDNA-IFN-gamma.

Application of immunoblotting to detect soluble Pneumocystis carinii antigen(s) in bronchoalveolar lavage of patients with Pneumocystis pneumonia and AIDS.

The technique of immunoblotting for detecting soluble Pneumocystis carinii antigen(s) in bronchoalveolar lavage fluid specimens from patients with AIDS and Pneumocystis pneumonia was evaluated. A soluble 67 kilodalton polypeptide that was immunoreactive with an anti-P carinii monoclonal antibody (2G2) was found in the supernatants of 26 lavage samples from patients with pneumocystosis. Intact organisms in lavage sediments were detected by methenamine silver or immunofluorescence staining procedures. The diagnostic use of this technique was shown in four cases in which lavage sediments proved negative for intact Pneumocystis carinii organisms on first examination; 2G2 reactive soluble antigen, however, was identified in the immunoblots of the supernatants from the same samples. It is concluded that immunoblotting of bronchoalveolar lavage specimens using 2G2 monoclonal antibody as a detection probe may be a useful adjunct to the morphological demonstration of organisms by special staining procedures.

Primary fibrosarcoma of the heart presenting as obstruction at the tricuspid valve: diagnosis by cross-sectional echocardiography.

We report a case of primary fibrosarcoma of the heart which presented with features of obstruction to the tricuspid valve and superior caval vein. It was correctly diagnosed by cross-sectional echocardiography.

Peripartum cardiomyopathy: prognostic variables at initial evaluation.

Twenty patients with peripartum cardiomyopathy were followed up for a period ranging from 6-14 months (mean 6 +/- 2 months). At initial evaluation, 16 patients were in New York Heart Association Class IV and the remainder in Class III. During follow up, 12 patients improved to Class I, 7 patients either failed to improve or deteriorated and one patient died. Certain variables at initial evaluation were related to prognosis. The patients who deteriorated, as compared to those who improved, were significantly older (30 +/- 6.8 vs 24 +/- 3 years, P less than 0.01), of higher parity (3 +/- 1 pregnancies vs 1.5 +/- 5 pregnancies, P less than 0.001) and had later onset of symptoms after delivery (7.6 +/- 4 weeks vs 3 +/- 1.3 weeks, P less than 0.001). They also had higher echocardiographic left ventricular end diastolic dimensions (7.0 +/- 8.4 cm vs 3.0 +/- 0.8 cm, P less than 0.001) and higher mean pulmonary arterial (38 +/- 4 mmHg vs 28 +/- 6 mmHg, P less than 0.001) and pulmonary arterial wedge pressures (24 +/- 2 mmHg vs 20 +/- 2 mmHg, P less than 0.001) at cardiac catheterization. Conduction defects were present on the surface electrocardiogram in all the patients who deteriorated, as compared to 4 patients who improved. In conclusion, certain variables at initial evaluation can help in identifying high risk subsets with peripartum cardiomyopathy.

Differential effects of autonomic blockade on sinus and atrioventricular nodal function in normals and in intrinsic sinus node dysfunction.

The effect of pharmacologic total autonomic blockade on sinus and atrioventricular nodes was studied in 10 normals and 21 patients with sick sinus syndrome with abnormal intrinsic corrected sinus node recovery time. In normals the intrinsic heart rate (113.3 +/- 11.6 beats/min) was higher than the resting heart rate (87.3 +/- 12 beats/min; P less than 0.001). The AH interval at an identical paced rate decreased from 119 +/- 36 msec to 93 +/- 17.6 msec after autonomic blockade (P less than 0.05). Mean atrial paced cycle length at AH Wenckebach block was not different during control and after drugs (319 +/- 46 msec vs. 311.5 +/- 39 msec; P = NS). Although sinus cycle length shortened in all cases after autonomic blockade, paced cycle length at AH Wenckebach increased (4) or remained unchanged (3) in 7 cases. Maximum normal "intrinsic" paced cycle length at AH Wenckebach was 390 msec (mean +/- 2 SD). In sick sinus syndrome, resting heart rate (66.3 +/- 18.8 beats/min) and intrinsic heart rate (74.6 +/- 16.4 beats/min) were similar (P = NS); AH at identical paced rate: control 136.6 +/- 54 msec, after drugs 130.5 +/- 35 msec (P = NS); cycle length at AH Wenckebach: control 380.5 +/- 73 msec, after autonomic blockade 383 +/- 49 msec (P = NS). Two of 3 cases with abnormal atrioventricular nodal response to atrial pacing during control normalized after autonomic blockade; 9/21 (42.8%) cases developed AH Wenckebach at cycle length greater than 390 msec after autonomic blockade. The data suggest that the autonomic nervous system has differential effects on sinus and atrioventricular nodes. Patients with sick sinus syndrome frequently have abnormalities of "intrinsic" atrioventricular nodal conduction unmasked by autonomic blockade.