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).

Role of Iron Therapy in Heart Failure: A Consensus Statement from India

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

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.

Acute effects of diets rich in almonds and walnuts on endothelial function

Objective Omega-3 fatty acids, especially alpha-linolenic acid (ALA), which are present in nuts may reduce cardiovascular disease (CVD) risk, by changing vascular inflammation and improving endothelial dysfunction. The objective of the study was to evaluate the acute effects of two different diets, one containing walnuts and the other almonds on endothelial function. Methods Twenty-seven overweight volunteers underwent a randomized 2-period, crossover, controlled intervention study. The subjects were given either walnut or almond diets which varied in monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content. The walnut diet provided 23.1% energy from PUFA and the almond diet provided 7.6% energy from PUFA. Endothelial function was assessed physiologically by flow-mediated dilation (FMD) and biochemically by sVCAM (soluble vascular cell adhesion molecules). Results The walnut diet significantly improved FMD (p = 0.004) and decreased sVCAM (p = 0.009) whereas the almond diet tended to improve FMD (p = 0.06) and significantly decreased sVCAM (p = 0.004). Conclusion Both walnut and almond diets improved FMD and sVCAM and there was no significant difference in physiological and biochemical markers between the two diets.

Prognostic significance of DNA index by flowcytometry in acute lymphoblastic leukaemia.

DNA index (DI) is considered an important prognostic factor in acute lymphoblastic leukaemia (ALL). We undertook this study to correlate DI with other presenting features and response to therapy. Of the 30 patients of ALL treated at our hospital and entered in this study, 15 were put on the aggressive MCP (multi center protocol) 841 protocol and equal number on the Alternate protocol. Eighteen achieved complete remission (13/15 on the former protocol and 5/15 on the later). DI was less than 0.8 in 8 (27%) patients, between 0.8 and 1.2 in 18 (60%) and more than 1.2 in 4 patients (13%). These figures are different from those reported in Caucasians. On multivariate regression analysis, the DI significantly correlated with percentage of blasts in peripheral blood (P = 0.0035). There was no correlation with outcome or response to treatment.

Acute non-lymphocytic leukemia with expression of surface antigen CD7--morphological, cytochemical, immunological and ultrastructural features in eight patients.

Of late, there has been an increase in the number of acute leukemias coexpressing markers believed to be restricted to a single lineage. Eight patients with ANLL whose blast coexpressed the T cell associated CD7 antibody were identified among 462 consecutive ANLL cases. Seven had FAB defined AML according to morphocytochemical criteria, whereas one patient was classified as MO on the basis of ultrastructural studies. The incidence of CD7 positivity was particularly significant in the less differentiated sub-types MO and M1 compared to other FAB sub-groups. Detailed long term studies will be required to realize their biological and clinical significance.

Intravenous streptokinase in acute evolving myocardial infarction--six to thirty-six months follow up.

270 consecutive patients who presented within six hours of the onset of acute myocardial infarction (AMI) and had no contraindication to thrombolytic therapy received intravenous infusion of 750,000 units of streptokinase (STK) in thirty minutes followed by heparin and oral anticoagulants. Treatment was instituted within 210 +/- 64 minutes after the onset of symptoms and reperfusion was achieved in 44 +/- 21 minutes. Reperfusion was recognised by indirect criteria in 249 patients, (92.2%) in the 0-6 hours group and 100% in the 0-3 hours group in all 72 patients. 2D echo LV ejection fraction (LVEF) improved from 51.6% +/- 9.4% at 0 hours to 60.61 +/- 8.4% at first week. In 40 patients (14.8%) there was early reocclusion in mean time of 36 +/- 13 hours of treatment. The incidence of reocclusion was higher in patients with anterior wall AMI than with inferior wall AMI. Reocclusion was also more frequent in patients who were administered adjuvant Dipyridamole therapy. In 36 of these patients reperfusion was achieved with an additional dose of streptokinase. During the last thirty-six months follow up, treadmill stress test was positive in 15 out of 80 (18.8%) streptokinase group subjected to it as compared to 42.2% conventionally managed patients. No LV thrombus, aneurysm or papillary muscle dysfunction was seen. 25 patients (9.2%) underwent coronary angiography six weeks later. CABG was undertaken in only 18 patients (6.6%) along with endarterectomy in one (.37%). None of the patients required additional aneurysmectomy or valve replacement. Elderly patients (above 75 years) suffered major haemorrhagic complications (.37%) and 17% of patients had minor bleeds. In-hospital mortality was 4.8% as compared to 10.2% in the control group (P less than .05). A long-term follow-up (6-36 months) revealed 11 patients that (4.07%) had reinfarction at mean time of 18 +/- 11 months (P less than .05). The late mortality rate in 6-36 months follow up was was 1.8% (P less than .05). It was concluded that intravenous streptokinase in acute myocardial infarction along with long-term anticoagulants is safe and effective. It reduces early and late mortality and morbidity significantly. A conservative strategy of subjecting patients to CABG after effective thrombolysis was found satisfactory during six to thirty-six months follow-up.

Pentoxifylline--a new drug for the treatment of intermittent claudication.

Pentoxifylline, a xanthine analogue was evaluated for efficacy, safety and tolerance in the treatment of intermittent claudication in a pilot study. Evaluation was performed in 35 cases. 20 patients were given Pentoxifylline in doses of 1200 mg daily, and 15 patients were given placebo for a period of 8 weeks respectively. Pentoxifylline given in doses of 1200 mg was significantly more effective than the placebo in increasing both the initial and absolute claudication distance (ICD & ACD) in patients with chronic occlusive arterial disease. The subjective parameters, such as paraesthesias, muscular cramps and sensation of heaviness in the legs paralleled the course of walking parameters. These results support the hypothesis that Pentoxifylline in doses of 400 mg TDS reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD (Fontaine Stage II or Stage III). Pentoxifylline is thus regarded as a promising drug for circulatory ischaemic disorders, especially in intermittent claudication. It was well tolerated with minimal untoward effects.