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Objective: To evaluate paroxysmal atrial fibrillation (AF) prevalence in Indian adults who completed 24-Hour Holter monitoring. Methods: A total of 23,847 patients (36.9 % women) were analyzed for AF duration using a software algorithm. Results: AF was diagnosed in 4153 (17.4 %) patients with a median AF duration of 13 min and 55 s. Conclusion: AF prevalence was high and largely untreated. The short duration of AF episodes indicates a low likelihood of detection during clinical visits, highlighting its potential underestimation in Indian healthcare.

Objective: Type 2 diabetes mellitus (T2DM) is known to be associated with development of left ventricular (LV) dysfunction and heart failure (HF). The study aimed to determine the prevalence of LV dysfunction and HF in unselected out-patients with T2DM with no previous cardiac history and to correlate LV dysfunction and HF with demographic and comorbid characteristics. Methods: This cross-sectional study conducted at 27 centers in India captured demographic and clinical data through electronic case record forms. B-type natriuretic peptide of >105 pg/mL was used to diagnose HF and two-dimensional echocardiography was used to assess LV dysfunction. Results: Of the 615 patients, 54.3 % (n = 334) were males; mean age was 57.4 ± 10.48 years. More than one-third of the patients had T2DM duration of >10 years (n = 238; 38.7 %), with hypertension as the most prevalent comorbidity (n = 372, 78.6 %). Approximately 61.3 % of the patients had LV hypertrophy. The mean LV mass was 135.0 ± 56.16 g (95 % CI 130.28, 139.70). The prevalence of any type of LV dysfunction, including systolic or diastolic dysfunction and HF was 55 % (95 % CI 51.0, 59.0) and 10 % (95 % CI 7.0, 12.0), respectively. A negligible but statistically significant correlation was observed between LV dysfunction and T2DM duration (p = 0.011), alongside HF and age (p

Background: Optical coherence tomography (OCT) is reported to be a feasible and safe imaging modality for the guidance of percutaneous coronary intervention (PCI) of complex lesions. Methods: This multicenter, prospective registry assessed the minimum stent area (MSA) achieved under OCT guidance. A performance goal of 24% improvement in MSA over and above the recommendation set by the European Association of Percutaneous Cardiovascular Interventions Consensus 2018 (4.5 mm2 MSA for non-left main and 3.5 mm2 for small vessels). The incidence of contrast-induced nephropathy was also assessed. Core lab analysis was conducted. Results: Five hundred patients (average age: 59.4 ± 10.1 years; 83% males) with unstable angina (36.8%), NSTEMI (26.4%), and STEMI (22%) were enrolled. The primary endpoint was achieved in 93% of lesions with stent diameter ≥2.75 mm (average MSA: 6.44 mm2) and 87% of lesions with stent diameter ≤2.5 mm (average MSA: 4.56 mm2). The average MSA (with expansion ≥80% cutoff) was 6.63 mm2 and 4.74 mm2 with a stent diameter ≥2.75 mm and ≤2.5 mm, respectively. According to the core lab analysis, the average MSA achieved with a stent diameter ≥2.75 mm and ≤2.5 mm was 6.23 mm2 and 3.95 mm2, respectively (with expansion ≥80% cutoff). Clinically significant serum creatinine was noted in two patients (0.45%). Major adverse cardiac events at 1 year were noted in 1.2% (n = 6) of the patients; all were cardiac deaths. Conclusion: PCI under OCT guidance improves procedural and long-term clinical outcomes in patients with complex lesions not just in a controlled trial environment but also in routine clinical practice.

Background: Low-density lipoprotein-cholesterol (LDL-C) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) progression. Although lipid lowering therapies remain the cornerstone of secondary ACSVD prevention, there exists residual dyslipidemia. The current study aimed to evaluate the real-world experience related to the treatment patterns and LDL-C control in Indian Acute Coronary Syndrome (ACS) patients. Methods: This was a real-world, descriptive, retrospective, observational, and multicentric study conducted across India. The data was collected for 1 year following the ACS event. The change in the levels of LDL-C from the baseline to the follow-up visits and the control of LDL-C, the change in lipid profile, lipoprotein levels, treatment patterns for lipid-lowering, and tolerability of existing treatments were evaluated. Results: Overall, 575 patients were included from 11 centers across India. The mean age of the patients was 52.92 years, with male predominance (76.35%). Although there was a significant reduction in the mean levels of LDL-C from the baseline [(122.64 ± 42.01 mg/dl to 74.41 ± 26.45 mg/dl (p

Abstract Macrophage apoptosis is a key contributor to the progression of atherosclerosis. Cyclophilin A, a monocyte secretory protein associated with the initiation of atherosclerosis has an inherent nuclease activity. This study reports the mechanism by which cyclophilin A causes apoptosis of macrophages and accelerates the progression of atherosclerosis. Aortic lesion formation and apoptosis were studied in New Zealand White rabbits (NZW) which were fed high‐fat diet (HFD) for 12 weeks. Using monocytes and HFD‐fed rabbits we demonstrate that cyclophilin A induces mitochondrial membrane potential loss and mitochondrial pore transition protein opening through caspase 3 activation. En face staining revealed a significant increase in the lesion area in HFD‐fed rabbits. Levels of glucose, cholesterol and proinflammatory cytokines were higher in these animals compared to rabbits fed with a normal diet. In the aorta of HFD‐fed rabbits, medial vascular smooth muscle cells were disorganized and there was a loss of integrity of the endothelium. An 8‐fold increase was seen in the number of apoptotic cells in the lesion area of HFD‐fed NZW rabbits which were associated with an elevation in plasma cyclophilin A levels. siRNA knockdown of cyclophilin A gene reduced activation of caspase 3 in macrophages. Treatment with cyclosporine A, an inhibitor of cyclophilin A, significantly attenuated apoptosis in macrophages. Our study indicates that inhibitors of proinflammatory cytokines such as cyclophilin A may arrest macrophage apoptosis and result in a regression of advanced atherosclerotic lesions.

Abstract Introduction Dosing frequency is an important factor influencing medication compliance in patients with heart failure (HF), which in turn is imperative in achieving the desired therapeutic outcome. Here we assessed the efficacy and safety of ivabradine prolonged-release (PR) once-daily (test) vs. ivabradine immediate-release (IR) twice-daily (reference) formulations in patients with stable chronic HF with systolic dysfunction. Methods Patients with sinus rhythm and heart rate (HR) ≥ 50 bpm, left ventricular ejection fraction ≤ 40% (HF with reduced ejection fraction), on guideline-based standard care, receiving a stable dose of ivabradine IR 5/7.5 mg twice daily for ≥ 1 month were enrolled in this randomized, double-blind, phase 3 non-inferiority study. Patients were randomly assigned 1:1 to ivabradine PR (10 mg/15 mg) based on the ivabradine IR dosage or continued ivabradine IR (5 mg/7.5 mg). The primary endpoint was change in resting ECG HR from baseline to the end of 3 months, assessed by 12-lead ECG. Safety assessments and 24-h Holter HR monitoring (in a subgroup of patients) were also performed. Non-inferiority was concluded if the upper limit of the 95% CI of the difference between the test and reference was less than the margin of 6.5 bpm in the per-protocol set. Results A total of 169 out of 180 randomized patients (93.9%) completed the study (PR = 84; IR = 85). The least-square mean (standard error [SE]) for change in HR from baseline to 3 months was 0.76 (1.188; 95% CI −1.59:3.11) in ivabradine PR vs. ivabradine IR, which was within the pre-specified margin of 6.5 bpm, confirming the non-inferiority of ivabradine PR. The change from baseline to 3 months was comparable between the treatment groups for 24-h Holter ECG monitoring (p = 0.3701), mean HR awake (p = 0.3423), and mean HR asleep (p = 0.1501). Thirty-nine treatment-emergent adverse events (TEAEs) were reported; the majority in both groups were of mild or moderate severity and were subsequently resolved. Seven serious adverse events were reported (ivabradine PR = 2; ivabradine IR = 5), of which one was fatal (ivabradine IR group). The bradycardia events reported were comparable between groups. Conclusion Ivabradine PR was found to be non-inferior to ivabradine IR in the management of patients with stable CHF, with a comparable safety profile. Once-daily ivabradine PR effectively maintained the HR in patients shifted from the ivabradine IR twice-daily regimen, and thus may aid in improving treatment compliance. Trial Registration CTRI/2018/04/013464 (Trial Registered Prospectively on 24/04/2018)

Coronary allograft vasculopathy fails to give a warning anginal pain due to denervation and often presents with acute coronary syndrome, ventricular dysfunction, or sudden cardiac death. Early diagnosis in a pediatric patient is difficult as it involves invasive coronary angiography or advanced imaging such as intravascular ultrasound or optical coherence tomography. A 12-year-old boy developed acute coronary syndrome, elevated troponins, and right bundle branch block, 5 years after cardiac transplantation and was treated with culprit-vessel angioplasty with a drug-eluting stent. Advanced imaging showed the involvement of nonculprit vessels too. In a detailed literature search, we failed to identify a similar clinical presentation and management in the subcontinent, hence our interest in publishing this report for educational value. Issues in diagnosis, management, prognosis, and prevention are discussed.

Objective: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults. Methods: A national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India. Results: Blood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18–19, 20–44, 45–54, 55–64, 65–74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively. Conclusion: There is a high prevalence of hypertension, with almost one in every three Indian adult affected. Keywords: Hypertension, India, Prevalence

Background: The impact of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for diagnosis and management of hypertension on the prevalence of hypertension in India is unknown. Methods: We analyzed data from the Cardiac Prevent 2015 survey to estimate the change in the prevalence of hypertension. The JNC8 guidelines defined hypertension as a systolic blood pressure of ≥140 ​mmHg or diastolic blood pressure of ≥90 ​mmHg. The 2017 ACC/AHA guidelines define hypertension as a systolic blood pressure of ≥130 ​mmHg or diastolic blood pressure of ≥80 ​mmHg. We standardized the prevalence as per the 2011 census population of India. We also calculated the prevalence as per the World Health Organization (WHO) World Standard Population (2000–2025). Results: Among 180,335 participants (33.2% women), the mean age was 40.6 ​± ​14.9 years (41.1 ​± ​15.0 and 39.7 ​± ​14.7 years in men and women, respectively). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%) and 2,878 (1.6%) participants belonged to age group 18–19, 20–44, 45–54, 55–64, 65–74 and ​≥ ​75 years respectively. The prevalence of hypertension according to the JNC8 and 2017 ACC/AHA guidelines was 29.7% and 63.8%, respectively- an increase of 115%. With the 2011 census population of India, this suggests that currently, 486 million Indian adults have hypertension according to the 2017 ACC/AHA guidelines, an addition of 260 million as compared to the JNC8 guidelines. Conclusion: According to the 2017 ACC/AHA guidelines, 3 in every 5 Indian adults have hypertension.

Background: Acute coronary syndrome (ACS) is associated with emergency hospitalizations, and there are limited real-world data on clinical outcomes in post-ACS Asian patients. This article presents data on the Indian subgroup from the Long-term Follow-up of Antithrombotic Management Patterns in Acute Coronary Syndrome Patients in Asia (EPICOR-Asia) study. Methods: EPICOR included patients with ACS [ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction (NSTEMI), or unstable angina (UA)]. The study had two phases: acute phase and follow-up phase. The primary objective was to describe short- and long-term antithrombotic management patterns. Results: EPICOR-India enrolled 2468 patients (STEMI-1482; NSTEMI-562; and UA-424). Cardiovascular risk factors were present in 1362 (55.2%) patients. Prehospital care was received by 879 (35.6%) patients, and the median time from the symptom onset to the first medical attention was 3 h (0.08, 100.33). The most common drug regimen prescribed during the acute phase was ≥2 antiplatelet agents + anticoagulants with no glycoprotein IIb/IIIa inhibitors and at discharge were aspirin + clopidogrel. About 78.8% of patients were discharged on dual antiplatelet therapy (DAPT) and 16%, on single antiplatelet therapy (SAPT). At 23 months after discharge, 55.6% were on DAPT, while 16.4% were on SAPT. Postdischarge outcomes at 2 years included death in 165 (6.7%) patients, composite events of death, myocardial infarction (MI), or ischemic stroke in 182 (7.4%) patients, and bleeding events in seven (0.3%) patients. Conclusion: This study showed a gap between international recommendations and implementation for managing ACS in Indian patients. Most of the patients prefer to undergo invasive management instead of non-invasive therapy. At the end of the 2-year follow-up, more than half of the population was receiving DAPT, with most patients on receiving a combination of aspirin and clopidogrel. The mortality along with composite events of death, MI, or ischemic stroke was highest for patients with NSTEMI. Keywords: EPICOR- India, ACS, Antithrombotic, DAPT, Myocardial infarction, STEMI, NSTEMI

Impairment of efferocytosis in apoptotic macrophages is a known determinant of the severity of atherosclerosis and the vulnerability of plaques to rupture. The precise mechanisms involved in impaired efferocytosis are unclear. Given the well-recognized role of the inflammatory cytokine cyclophilin A (Cyp A) in modulating several atherogenic mechanisms in high-glucose primed monocytes, we investigated the role of Cyp A in macrophage efferocytosis. The efficiency of efferocytosis in RAW 264.7 macrophages grown in vitro and primed with cyclophilin A was assessed using flow cytometry and confocal assays. Cholesterol content in cells was measured using cell-based cholesterol efflux assay. Proteomic analysis and bioinformatics tools were employed to decipher the link between cyclophilin A and the known ligand receptors involved in efferocytosis. Cyclophilin A was found to impair efferocytosis in apoptotic macrophages by reducing ABCA1-mediated cholesterol efflux in foam cells derived from macrophages. Cyclophilin A-primed macrophages showed an increase in expression of the don’t-eat-me signal CD 47 and a decrease in the expression of the eat-me signal, calreticulin. Phagocytosis was restored upon silencing of cyclophilin A. New Zealand white rabbits were fed a high-fat diet, and lesions in their aortae were analyzed histologically for evidence of atherosclerosis and the expression of Cyp A, CD 47 and calreticulin, the ligand receptor involved in efferocytosis. Gene and protein expressions in aortae and macrophages were analyzed by real-time PCR and Western blotting. Cyclophilin A, via its effects on the expression of CD 47 and calreticulin, impairs efferocytosis in apoptotic macrophages. Together with its impact on cholesterol efflux from macrophages, these effects can amplify other mechanisms of Cyp A in accelerating the progression of atherosclerosis.

The TN STEMI Program was a multicenter, prospective, observational study conducted in Tamil Nadu, India, that assessed the effects of implementing the STEMI India Model for the management of STEMI. We discuss the economic and societal impact in this article. Given that the intervention resulted in an absolute mortality reduction of 3.4%, we calculated a number needed to treat of 30 patients. At an annualized project cost of INR 15.11 million, this approximately calculates to INR 193,749 (USD 3,311) per life saved. The utility of the TN-STEMI Program can be estimated to be 1,108 life-years. This calculates to approximately INR 13,643 (USD 233) per life-year saved. Our estimates will likely be of particular interest to policy makers in low and middle-income countries, where financial and resource constraints pose a perennial public health challenge.

Diabetes mellitus (DM) is a pandemic disease and an important cardiovascular (CV) risk factor. The atherogenic dyslipidemia in diabetes (ADD) is characterized by high serum triglycerides, high small dense LDL levels, low HDL levels and postprandial lipemia. Insulin resistance is a primary cause for ADD. Though statins are highly effective for CVD prevention in DM but a significant residual CV risk remains even after optimal statin therapy. Fibrates, niacin and omega-3 fatty acids are used in addition to statin for treatment of ADD (specifically hypertriglyceridemia). All these drugs have some limitations and they are far from being ideal companions of statins. Many newer drugs are in pipeline for management of ADD. Dual PPAR α/γ agonists are in most advanced stage of clinical development and they have a rational approach as they control blood glucose levels (by reducing insulin resistance, a primary factor for ADD) in addition to modulating ADD. Availability of dual PPAR α/γ agnosits and other drugs for ADD management may improve CV outcomes and decrease morbidity and mortality in diabetic patients in future.