Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ?-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

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.

Lipoprotein (a) and lipid levels in young patients with myocardial infarction and their first-degree relatives.

BACKGROUND: Studies among emigrant Indians have stressed the role of a powerful genetic factor, lipoprotein (a), in the causation of premature coronary artery disease. This study was carried out to assess lipoprotein (a) and lipid levels in 50 consecutive young north Indian patients (age less than 45 years, mean age 39+/-3.7 years) with myocardial infarction, their first-degree relatives (n=125, mean age 36+/-16 years), and age- and sex-matched controls (n=50, mean age 34+/-6.9 years). METHODS AND RESULTS: Blood samples for lipid estimation were taken within 24 hours of myocardial infarction and after overnight fasting for twelve hours. Lipoprotein (a) levels were estimated by the ELISA technique using preformed antibodies while lipid levels were estimated by kits using the colorimetric method. All were male patients. The mean lipoprotein (a) level was 22.28+5.4 mg/dl in patients, 13.88+5.19 mg/dl in their first-degree relatives and 9.28+22.59 mg/dl in controls. In addition, it was significantly higher in young patients with myocardial infarction and their relatives as compared to controls (p<0.001 for patients v. controls and p<0.05 for relatives v. controls). There was no significant difference in the levels of total cholesterol and low-density lipoprotein cholesterol among the three groups. High-density lipoprotein cholesterol was significantly lower in young patients with myocardial infarction (30.16+/-9.45 mg/dl) and their first-degree relatives (33.28+/-8.45 mg/dl) as compared to controls (46.8+/-8.04 mg/dl) (p<0.001 for patients v. controls and p<0.01 for relatives v. controls). Triglyceride levels were significantly higher in patients as compared to controls (202+/-76 mg/dl v. 149 + 82.99 mg/dl, p<0.05). Smoking was more prevalent in young patients with myocardial infarction as compared to controls (44% v. 36%, p<0.05). CONCLUSIONS: Smoking, high lipoprotein (a) and triglyceride levels and low high-density lipoprotein levels may be important risk factors for coronary artery disease in the younger population; also, there is familial clustering of high lipoprotein (a) levels in first-degree relatives of young patients with myocardial infarction.

Coronary stent implantation without lesion predilatation (direct stenting): our experience with this evolving technique.

BACKGROUND: Until recently, conventional intracoronary stent deployment required predilatation of the lesion with a balloon. However, "direct stenting" of the lesion without predilatation offers certain theoretical and practical advantages. We assessed the safety and feasibility of direct stenting in a select group of patients who were likely to benefit most from these advantages, namely, those with acute coronary syndromes. saphenous vein graft lesions, associated renal or left ventricular dysfunction and those requiring multivessel intervention. METHODS AND RESULTS: After direct stenting, intravascular ultrasound was used to assess the adequacy of stent expansion in 51 patients. One hundred and twenty patients with a total of 125 lesions (83.3% males, average age 54.6+/-12.4 years) were enrolled for direct stenting. Of these, 90% of patients had presented with acute coronary syndromes, 21.6% of patients had associated moderate-to-severe left ventricular systolic dysfunction, 6.7% of patients had associated renal dysfunction and 30.8% of patients required multivessel intervention. Angiographically visible thrombus was present in 35.2% of patients. The mean reference diameter of the lesion was 3.18+/-0.32 mm and mean percentage diameter stenosis was 76.4+/-11.2%. Almost all varieties of stents were used (8.8% bare and 91.2% mounted). Procedural success was achieved in 98.3% of patients (98.4% of lesions). In two cases, the lesion had to be predilated prior to stenting. On angiography, the need for postdilatation of the stent was apparent in 29 (23.6%) lesions. In contrast, on intravascular ultrasound evaluation done in 51 lesions after stent deployment, the need for postdilatation to optimize stent expansion was seen in 43 (84.3%) lesions. There was one instance of acute stent thrombosis and two instances of slow-flow phenomenon. There were no deaths, myocardial infarction or need for urgent bypass surgery. CONCLUSIONS: We conclude that direct stenting is feasible and safe in selected groups of patients. Optimization of stent expansion after direct stenting may often require aggressive postdilatation.

Coronary stent thrombosis: time course and clinical outcome.

The current clinical practice of stent implantation has changed over the last few years. We analysed the incidence and time course of stent thrombosis in patients undergoing successful coronary angioplasty and stenting over the last three years. All the patients were treated with aspirin and ticlopidine. A total of 13 patients experienced stent thrombosis. The mean age was 52+/-12 years; 12 were smokers and 10 had a recent history of myocardial infarction. None of these patients had received abciximab. The median time from stent implantation to stent thrombosis was 10 hours, with all the stent occlusions occurring within 18 hours of stent implantation procedure. All the patients underwent a repeat intervention at a median time of 30 minutes after the clinical suspicion of stent occlusion. On follow-up of 1 to 24 months, three patients developed reocclusion. In the present era of coronary angioplasty and stenting, when interventional procedures are not pre-planned and patients are treated with aspirin and ticlopidine or clopidogrel at the time of stent implantation, the incidence of stent thrombosis is low; it is seen mainly in patients with recent myocardial infarction, majority of them being smokers, and occurs within 18 hours in all the patients.