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.

Demonstration of acid-fast bacilli in buffy coat and bone marrow smear--a diagnostic tool in pulmonary tuberculosis.

Buffy coat smears prepared from peripheral blood and bone marrow aspirate obtained from proved 60 untreated cases of pulmonary tuberculosis were stained with Ziehl-Neelsen method and thoroughly screened for presence of tubercle bacilli. Acid-fast bacilli were detected in 55% cases in buffy coat, 48.3% cases in bone marrow, 38.3% cases both in buffy coat and bone marrow and 65% cases either in buffy coat or in bone marrow or in both. Considering the fact that demonstration of acid-fast bacilli may not be possible in more than 25-50% of the suspected cases of tuberculosis, these techniques are recommended for evaluation of their utility in establishing diagnosis of tuberculosis, particularly in reference to sputum negative cases of pulmonary tuberculosis and tuberculosis of inaccessible extrapulmonary sites.

Effect of adenosine and inosine on carbon tetrachloride-induced liver damage in rats.

Liver damage induced in rats by carbon tetrachloride (CCL4) was obvious macroscopically as well as microscopically in stained sections. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (gamma-GT) were also significantly raised. Adenosine and inosine effectively countered the damage when these were given before and during the period during which CCl4 produces the typical damage. The beneficial effect was seen in biochemical as well as pathological studies.

Patterns of erythropoiesis and anaemia in malaria.

Of 138 patients with malaria, 90 were found to be having Plasmodium falciparum in their peripheral blood smears. Megaloblastosis alone or in combination with the other patterns of erythropoiesis was observed in 82.1 percent cases of chronic P. falciparum malaria as compared to 36.3 and 26.5 per cent cases of acute P. falciparum and P. vivax malaria respectively. Iron deficiency was observed in 15.5 percent cases of chronic P. falciparum, 18.2 per cent cases of acute P. falciparum and 13.3 per cent patients of P. vivax infection. Of patients with chronic falciparum malaria, 33.3 percent revealed features of both megaloblastosis and defective iron utilization and transient hypoplasia of marrow was observed in 8.9 per cent of these cases.

Carcinoembryonic antigen and human chorionic gonadotrophin in breast carcinoma and prostatic specific acid phosphatase in prostate carcinoma.

Tumour markers viz carcinoembryonic antigen (CEA), human chorionic gonadotrophin (HCG) in 30 cases of carcinoma breast and prostatic specific acid phosphatase (PSAP) in 30 cases of carcinoma prostate were studied by peroxidase antiperoxidase technique in paraffin blocks of tissue. Twenty three (76.7%) and 20 (66.7%) cases were positive for CEA and HCG respectively. No correlation was observed between CEA and HCG status, and histological differentiation of the tumours. All the 29 cases (100%) of adenocarcinoma prostate were PSAP positive while a single case, negative for PSAP, was of transitional cell carcinoma.

Chronic granulocytic leukaemia presenting with mandibular mass.

A case of chronic granulocytic leukaemia with extramedullary deposits in the mandible is reported. Systemic chemotherapy coupled with local irradiation resulted in regression of the mandibular mass.

Bacillaemia and bone marrow involvement in leprosy.

Fifty patients (24 new and 26 receiving specific treatment) of leprosy were investigated to study the concentration and morphological index (MI) of the lepra bacilli in skin, peripheral blood and bone marrow. The organisms were detected in 28 cases on skin slit smear examination, in 38 cases on bone marrow examination and in 38 cases on examination of smears made from buffy coat of peripheral blood. Out of 22 cases negative for the bacilli on skin slit smears, 15 had the organisms either in buffy coat or bone marrow or both. Acid fast bacilli in peripheral blood and bone marrow with skin smear negativity were mainly observed in patients with paucibacillary type of the disease and in those who were receiving treatment. Examination of buffy coat and bone marrow for presence of lepra bacilli is suggested to establish the diagnosis in doubtful cases.

Sex chromatin in female breast tumour.

The incidence of sex chromatin in tumour cell nuclei was estimated in twenty five cases each of carcinoma and fibroadenoma breast using haematoxylin and eosin, thionine, aceto-orcein and Papanicolaou's stains on imprint-smears. The sex chromatin incidence in fibroadenoma was found similar to that of normal breast tissue but the incidence markedly decreased in carcinoma breast. Undifferentiated tumours with histologic grade III, nuclear grade I, no lymphocytic infiltrate and involvement of overlying skin, nipple and areola were more often associated with low sex chromatin incidence. No relationship was observed between sex chromatin incidence and tumour size or axillary lymph node metastasis.