Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Familial hypercholesterolemia.

Familial hypercholesterolemia is a common genetic disorder of autosomal inheritance associated with elevated LDL-cholesterol. It is estimated to affect 1:250 individuals in general population roughly estimated to be 5 million in India. The prevalence of FH is higher in young CAD patients (<55 years in men; <60 years in women). FH is underdiagnosed and undertreated. Screening during childhood and Cascade screening of family members of known FH patients is of utmost importance in order to prevent the burden of CAD. Early identification of FH patients and early initiation of the lifelong lipid lowering therapy is the most effective strategy for managing FH. FH management includes pharmaceutical agents (statins and non statin drugs) and lifestyle modification. Inspite of maximum dose of statin with or without Ezetimibe, if target levels of LDL-C are not achieved, Bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibitors/Inclisiran can be added.

Exercise and lipids.

Evidence from the existing literature suggests that exercise has positive effects for prevention and treatment of cardiovascular diseases by reducing risk factors such as elevated blood lipids. Based on clinical and observational clinical trials, it is well established that increased physical activity and regular exercise has a favourable impact on blood lipids and lipoprotein profiles. Exercise training significantly decreases blood triglycerides concentration and increases high density lipoprotein cholesterol levels. Though the Indian data depicting the effect of exercise on lipids is scarce, exercise directly improves "atherogenic dyslipidaemia" which is frequently present among Indians i.e. HDL-C is increased, TG is reduced and LDL-C particle size is improved. While drug therapy is key to the treatment of dyslipidaemia, lifestyle alterations such as exercise should continue to be actively promoted and encouraged by clinicians. Exercise is a low cost, non pharmacological therapeutic lifestyle change that is of value to lipid metabolism and cardiovascular fitness.

Management of Heart Failure in a Resource-Limited Setting: Expert Opinion from India.

Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patients with heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies.

Prevalence of cardiac abnormalities and heart failure in unselected out-patients with type 2 diabetes mellitus and associated clinical factors: Real-world evidence from an Indian registry.

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 < 0.0001). CONCLUSION: Real-world data from this registry from India demonstrates a substantial burden of LV dysfunction and HF in individuals with T2DM in India. It is imperative to formulate strategies for early identification of LV dysfunction in individuals with T2DM for prevention and consequent management of HF.

The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement.

;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Improving the ACS Triage-Using High Sensitivity TroponinI and Copeptin for Early 'Rule-Out' of AMI.

Rule-out of acute myocardial infarction (AMI) in patients presenting with acute chest pain at the emergency department (ED) is a major challenge across the globe. Patients presenting very early with chest pain may provide a diagnostic challenge even when using a cardiac necrosis specific biomarker, high sensitivity troponin (hs-Tn) as they are elevated at 3-6 h after the symptom onset. Copeptin is a marker of acute hemodynamic stress which is released within few minutes of the occurrence of MI and is elevated immediately at the presentation of patients with AMI. This indicates a complementary pathophysiology and kinetics of these two biomarkers. Hence, we evaluated whether or not a protocol with combined testing of copeptin and hs-TnI at admission in patients presenting with chest pain within 6 h in low to intermediate risk and suspected ACS leads to an earlier diagnosis of AMI and thereby, aids to prevent a higher proportion of major adverse cardiac events than the current standard protocol followed in ED. A total of 148 patients as per the inclusion criterion were recruited for the study. The dual biomarker copeptin and hs-TnI allows a rule-out of AMI at presentation with a sensitivity of 100% and NPV of 99.8%. Hence, the use of dual biomarker in conjunction with clinical assessment may obviate the need for a prolonged stay in the ED and retesting hs-TnI after 2 h (for delta check) in more than two-thirds of the patients. The inclusion of these tests could have an impact on the economic burden of the ED without jeopardizing the outcome for the patient.

Molecular studies in familial dilated cardiomyopathy - A pilot study.

Aim: To study genetic variants in patients of familial dilated cardiomyopathy. Methodology: Patients with reduced ejection fraction of less than 45% and dilated left ventricle are considered to have dilated cardiomyopathy. Clinical history was taken and possible secondary causes of dilated cardiomyopathy were excluded. Family history of ≥2 affected relatives or sudden cardiac death in a relative with age less than 35 years were included. Such patients blood sample were sent for next generation sequencing and analysed for presence of genetic variants. Results: As part of pilot study 20 patients (44% were female and 66% were male) were included. There was presence of 16 different pathogenic variants in 14 patients. Two patients had more than one variants in them. Most common of which were sarcomeric mutations constituting 32%. Titin followed by Filamin, Lamin and Desmosomal where the most commonly repeated mutations. Discussion: In our patients of familial dilated cardiomyopathy, 70% were detected to have pathogenic variants in them. Most common variations were seen on Titin gene. Thus those with familial dilated cardiomyopathy should be considered for next generation sequencing. First degree relatives of those with pathogenic variants should be screened using cascade testing for earlier detection and disease monitoring in them.

A Retrospective, Observational, EMR-Based Real-World Evidence Study to Assess the Incidence of Pedal Edema in Essential Hypertensive Patients on Amlodipine or Cilnidipine.

INTRODUCTION: Calcium channel blockers have pedal edema as one of the confining factors of treatment. A real-world study may help evident reality of the situation in regular Indian clinical practice. The aim of the study is to assess effectiveness and incidence of pedal edema in essential hypertensive patients treated with amlodipine or cilnidipine monotherapy. METHODS: Retrospective EMR data of adult essential hypertensive patients, prescribed amlodipine (n = 800) or cilnidipine (n = 800) as monotherapy, were analyzed. Incidence of pedal edema from baseline visit was analyzed in terms of dose and duration of treatment. The changes in systolic (SBP) and diastolic blood pressure (DBP) from baseline and proportion of patients achieving target BP goals were assessed. RESULTS: In amlodipine and cilnidipine groups, mean changes in SBP and DBP from baseline to end of the study period were 28.4 and 15.1 mmHg and 24.3 and 13.5 mmHg, respectively (p value <0.05). More than 50% of patients in both groups achieved BP goal at the end of the study (p value 0.266). In amlodipine group, total 23.9% reported pedal edema, while in cilnidipine, 27.6% (p value 0.0863). At the end of the study, 3.5% and 8.2% of patients remain with pedal edema, respectively, in both groups (pvalue <0.005). CONCLUSION: Amlodipine demonstrated greater BP reduction at a lower average dose, better efficacy, and tolerability in terms of pedal edema count as a lesser number of patients reported edema at the end of the study and a higher percentage of patients continued the prescribed baseline dosage regimen as compared to cilnidipine. Thus, the study established amlodipine as an effective and well-tolerated antihypertensive for Indians.

Achieving the Latest American Heart Association and American College of Cardiology Therapeutic Goals for Hypertension With Combination Therapy and Its Effects on Blood Pressure and Central Hemodynamic Parameters.

The present United States and European treatment guidelines recommend that antihypertensive therapy be initiated with a combination of agents from different classes to facilitate the achievement of control of blood pressure (BP). This prospective, randomized, open-label study was conducted at 3 tertiary hospitals in India to evaluate the effects of combination therapy with an angiotensin receptor blocker and a calcium antagonist on office BP and central hemodynamic parameters in patients with untreated hypertension or uncontrolled BP (>130/>80 mm Hg) during treatment with antihypertensive monotherapy. Patients were randomized to treatment with telmisartan 40 mg/day + amlodipine 5 mg/day or telmisartan 40 mg/day + cilnidipine 10 mg/day. Change from baseline to 8 weeks of treatment was assessed for seated office BP, ambulatory BP monitoring, and seated central hemodynamics (central BP, aortic augmentation index, central aortic augmentation pressure, and pulse wave velocity). A total of 94 of 96 enrolled patients completed the study. From baseline to 8 weeks a significant decrease was observed in both telmisartan + amlodipine and telmisartan + cilnidipine groups for mean BP (148.0 ± 12.80 to 124.0 ± 10.4 and 144.5 ± 10.2 to 123.0 ± 10.0 mm Hg, respectively; both p <0.001); in only telmisartan + amlodipine group for mean central aortic systolic and diastolic BP (131.1 ± 19.1 to 119.7 ± 14.9 mm Hg [p <0.001] and 93.3 ± 12.0 to 89.2 ± 14.6 mm Hg [p = 0.0008], respectively) and for central aortic pulse wave velocity (7.6 ± 1.4 to 7.2 ± 1.3 m/s, p = 0.0011); in only telmisartan + cilnidipine group for aortic augmentation index (27.5 ± 14.6 to 22.3 ± 12.2; p = 0.0178). Heart rate was unchanged in both treatment groups. Combination therapy with an angiotensin receptor blocker and a calcium antagonist effectively reduced BP to below the new <130/80 mm Hg target and had favorable effects on central hemodynamics.

Therapeutic adherence in hypertension: Current evidence and expert opinion from India.

Hypertension (HTN) is a globally prevalent non-communicable disease contributing significantly to cardiovascular (CV) morbidity and mortality. In achieving control of HTN, therapeutic adherence plays a crucial role. Studies from India identify varying rates of adherence to antihypertensive medications. Multiple factors determine treatment adherence in HTN. In India, factors such as lower socioeconomic status, health literacy, asymptomatic nature of disease, forgetfulness, cost of medications, and duration of HTN determine the adherence. An excellent physician-patient relationship incorporating adequate counseling along with the use of other methods can identify poor adherence. Improving adherence necessitates incorporating a multipronged approach with strategies directed at physicians, patients, and health systems. With innovation in therapeutics, the pharmaceutical sector can contribute significantly to improve adherence. Furthermore, increasing adherence to lifestyle interventions can help achieve better HTN control and improve CV outcomes. In the Indian context, more emphasis is necessary on patient education, enhanced physician-patient relationship and communication, increased access to health care, and affordability in improving therapeutic adherence in HTN.

Therapeutic experience of ticagrelor in Indian patients with acute coronary syndrome: A non-interventional, prospective, and observational study.

OBJECTIVE: This observational study was designed to understand the usage pattern of ticagrelor in real-life clinical practice among a large number of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical management (MM). The study also recorded clinical events, i.e., bleeding, dyspnea, and cardiovascular (CV) events, reported by the investigator during the follow-up period. METHODS: The ACS patients aged ≥18 years hospitalized for ACS and were prescribed ticagrelor upon discharge or ≤1 month and patients who underwent PCI, CABG, or MM for ACS were enrolled. The subjects were followed up for a period of up to 12 months. The data were collected on a case report form. RESULT: The study recruited 2997 subjects from 49 sites in India. Approximately half of the ACS subjects had ST segment elevation myocardial infarction (48.9%), and PCI was used as management in 92.4% subjects. The mean (±SD) duration of use of ticagrelor was 314 (±110.2) days over a period of 12 months. Of 136 subjects (4.5%) who experienced any clinical events, CV deaths were reported in 20 (0.7%), myocardial infraction in 19 (0.6) subjects and ischemic stroke in 23 (0.8%) subjects, and severe dyspnea was reported in 68 (2.2%) subjects. Out of 33 bleeding cases, 25 (0.8%) subjects had thrombolysis in myocardial infarction (TIMI) minimal, seven (0.2%) had TIMI minor, and one TIMI major. Platelet inhibition and patient outcomes (PLATO) major was reported in two subjects and CABG bleed in one subject. The incidence of PLATO defined major and minimal bleeding were lower in subjects undergoing fibrinolysis than overall population. CONCLUSION: Ticagrelor has been used across ACS types and in different management strategies in real world settings in India. The incidence of clinical events was lower as compared with data in literature. ClinicalTrials.gov Identifier: NCT02408224.

Prevalence of familial hypercholesterolemia in premature coronary artery disease patients admitted to a tertiary care hospital in North India.

AIMS: The prevalence of premature coronary artery disease (CAD) in India is two to three times more than other ethnic groups. Untreated heterozygous familial hypercholesterolemia (FH) is one of the important causes for premature CAD. As the age advances, these patients without treatment have 100 times increased risk of cardiovascular (CV) mortality resulting from myocardial infarction (MI). Recent evidence suggests that one in 250 individuals may be affected by FH (nearly 40 million people globally). It is indicated that the true global prevalence of FH is underestimated. The true prevalence of FH in India remains unknown. METHODS: A total of 635 patients with premature CAD were assessed for FH using the Dutch Lipid Clinical Network (DLCN) criteria. Based on scores, patients were diagnosed as definite, probable, possible, or no FH. Other CV risk factors known to cause CAD such as smoking, diabetes mellitus, and hypertension were also recorded. RESULTS: Of total 635 patients, 25 (4%) were diagnosed as definite, 70 (11%) as probable, 238 (37%) as possible, and 302 (48%) without FH, suggesting the prevalence of potential (definite + probable) FH of about 15% in the North Indian population. FH is more common in younger patients, and they have lesser incidence of common CV risk factors such as diabetes, hypertension, and smoking than the younger MI patients without FH (26.32% vs.42.59%; 17.89% vs.29.44%; 22.11% vs.40.74%). CONCLUSION: FH prevalence is high among patients with premature CAD admitted to a cardiac unit. To detect patients with FH, routine screening with simple criteria such as family history of premature CAD combined with hypercholesterolemia, and a DLCN criteria score >5 may be effectively used.

Short- and long-term follow-up of antithrombotic management patterns in patients hospitalized with acute coronary syndrome: Indian subgroup of EPICOR Asia study.

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.

Ambulatory blood pressure monitoring in clinical practice.

Being one of the most widely prevalent diseases throughout the world, hypertension has emerged as one of the leading causes of global premature morbidity and mortality. Hence, blood pressure (BP) measurements are essential for physicians in the diagnosis and management of hypertension. Current American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend initiating antihypertensive medications on the basis of office BP readings. However, office BP readings provide a snapshot evaluation of the patient's BP, which might not reflect patient's true BP, with the possibility of being falsely elevated or falsely low. Recently, there is ample evidence to show that ambulatory blood pressure monitoring (ABPM) is a better predictor of major cardiovascular events than BP measurements at clinic settings. ABPM helps in reducing the number of possible false readings, along with the added benefit of understanding the dynamic variability of BP. This article will focus on the significance of ambulatory BP, its advantages and limitations compared with the standard office BP measurement and a brief outlook on its use and interpretation to diagnose and treat hypertension.

Heart Rate in Hypertension: Review and Expert Opinion.

Heart rate (HR) is strongly associated with both peripheral and central blood pressures. This association has implications in hypertension (HTN) prognosis and management. Elevated HR in HTN further elevates the risk of adverse outcomes. Evidence suggests that HR is an independent risk factor for cardiovascular (CV) and total mortality in patients with HTN. With objective to engage physicians and researchers in India to identify and discuss the implications related to HR management in HTN, experts in the HTN management provided consensus recommendations. The key expert recommendations included the following. (i) Heart rate (HR) has inverse relationship with the central aortic pressure, whereby reduction in HR is associated with an increase in central aortic pressure. This counter-balances the benefit of HR reduction with the harmful effects of rising central aortic pressure. (ii) Increase in the resting HR is associated with increased risk of incident HTN. A linear association between the two is observed especially in individuals with HR >80 bpm. (iii) A reduced HR variability further adds to the propensity for the development of HTN, especially in men. (iv) Each 10 beats per minute increase in the resting HR can substantially increase the risk of adverse CV and mortality outcomes. On treatment HR provides a better prognostic guide. (v) Ambulatory HR with day-time and night-time HR evaluation may also suggest different impact on outcomes. (vi) Target HR in patients with HTN remains unclear. Generally, HR<70 bpm on beta blocker (BB) treatment is advised which may be further lowered in patients with comorbidities like heart failure and coronary artery disease. (vii) Adopting healthy lifestyle approaches to keep check on BP and HR is essential. (viii) Use selective beta-1 blocker in symptomatic cases with elevated HR beyond 80-85 mmHg. BBs are expected to benefit by lowering HR by nearly 10 bpm. Preference should be given to newer beta-blockers which reduce HR and both peripheral and central blood pressure to derive comprehensive advantage of this dual action. (ix) It still remains unclear whether reducing HR in HTN without comorbidities alters the CV and mortality outcomes.

Adaptation of 2016 European Society of Cardiology/European Atherosclerosis Society guideline for lipid management to Indian patients - A consensus document.

In the year 2016, European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines provided recommendations on dyslipidemia management. The recommendation from these guidelines are restricted to European subcontinent. To adapt the updated recommendations for Indian subset of dyslipidemia, a panel of experts in management of dyslipidemia provided their expert opinions. This document provides expert consensus on adapting 2016 ESC dyslipidemia guidelines recommendations in Indian setting. The document also discussed India-specific relevant literature to support the consensus opinions provided in management of dyslipidemia.