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.

Arterial and venous thrombosis in a patient with Covid-19: A unique presentation

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection not only affects the respiratory system but also induces coagulation abnormalities and thrombosis. We report a middle-aged woman who presented during the Covid-19 pandemic with sudden-onset acute left upper limb ischaemia of short duration, with no history of dry cough, breathlessness or fever, and tested positive on TrueNAT for SARS-CoV-2. Later, she developed deep venous thrombosis of the right lower limb during isolation in the hospital.

Endothelium-dependent brachial artery flow mediated vasodilatation in patients with diabetes mellitus with and without coronary artery disease.

AIM OF THE STUDY: Endothelial function as assessed by brachial artery flow mediated vasodilatation (FMD) has been shown to be impaired in patients with coronary artery disease (CAD). Since diabetes mellitus (DM) has been considered to be CAD risk-equivalent, we sought to determine whether endothelial dysfunction is present in patients with DM independent of presence of CAD. METHODOLOGY: One hundred and ninety eight individuals were included in the study and divided into four groups: Group 1--patients with risk factors for CAD, but no DM or CAD; Group 2--patients with DM but no CAD; Group 3--patients with CAD but no DM and Group 4--patients with both DM and CAD. Brachial artery FMD assessment was performed once in all subjects and FMD was calculated as percentage increase in brachial artery diameter in response to increase in brachial artery flow. RESULTS : Mean FMD was significantly higher in Group 1 (7.03 +/- 2.87%) compared to the other three groups. Mean FMD in Group 2 (5.51 +/- 2.12%) was similar to that in Group 3 (4.56 +/- 2.70%; p value 0.195) but significantly higher than that in Group 4 (4.26 +/- 1.93%; p value 0.038). There was no statistically significant difference in mean FMD in Group 3 and Group 4 (p value 0.65). CONCLUSION : Endothelial function as assessed by FMD is significantly impaired in diabetics compared to non-diabetics in absence of CAD. In addition, similar degree of impairment in endothelial function is seen in diabetics without CAD and non-diabetic patients having CAD, implying CAD risk-equivalence of diabetes.

Comparison of impact strength of acrylic resin reinforced with kevlar and polyethylene fibres.

The present study was done to evaluate the impact strengths of heat-activated acrylic resins reinforced with Kevlar fibres, polyethylene fibres and unreinforced heat activated acrylic resin. Each of three groups had 25 specimens. Brass rods of uniform length of 40 mm and diameter of 8 mm were used to prepare the moulds. A combination of long fibres (40 mm length) and short fibres (6 mm length) were used. The total amount of fibres incorporated was limited to 2% by weight of the resin matrix. Short and long fibres of equal weight were incorporated. The short fibres were mixed with polymer and monomer and packed into the mould, while, the long axis of the specimen, perpendicular to the applied force. The specimens were then processed. Impact strength testing was done on Hounsfield's impact testing machine. Kevlar fibre reinforced heat activated acrylic resin specimens recorded higher mean impact strength of 0.8464 Joules, while polyethylene fibres reinforced heat activated acrylic resin recorded mean impact strength of 0.7596 joules. The unreinforced heat activated acrylic resin recorded mean impact strength of 0.3440 Joules.

Myoglobinuria and transient acute renal failure in a patient revealing hypothyroidism.

Muscle involvement in hypothyroidism commonly manifests as fatigue, myalgias, stiffness and slowed reflexes. We report a case of transient acute renal failure related to rhabdomyolysis and myoglobinuria in a 40 year old man that revealed the diagnosis of hypothyroidism with myopathy. The patient had proximal muscle weakness and tenderness, markedly raised muscle enzymes and deranged renal functions that normalised with thyroid replacement therapy. Hypothyroidism, though rare, should be considered a definite and authentic cause of rhabdomyolysis.

Pedicled omental transfer for ischaemic limbs--a 5-year experience.

Chronic occlusive arterial diseases form a single largest entity amongst the peripheral vascular diseases. Current operative methods available for improving circulation often elicit poor results and the patient has to undergo an amputation. The technique of pedicled omental transfer has given hope of saving such unsalvageable limbs. Although symptomatic and clinical improvement has been reported by this method of "biological by-pass revascularisation", there are no simple, objective and easily reproducible tests to assess improvement in circulation. In this study pulse oximetry and stress testing have been used to assess revascularisation. This study comprised 56 patients (78 limbs) suffering from chronic occlusive arterial disease, spanning a period of 5 years. Patients were investigated and subjected to pedicled omental transplantation (omentopexy). Symptomatological assessment showed improvement in intermittent claudication in about 85% of patients, relief from rest pain in 86% and healing of chronic ulcers in 73% of patients. Objective tests of stress testing and pulse oximetry also showed improvement in circulation. Relief from ischaemia was more in cases of Buerger's disease (TAO) than in cases of atherosclerosis obliterans (ASO).

An evaluation of closest speaking space using various sibilants amongst age groups of both sexes.

Closest speaking space plays a crucial role in the success of complete denture prosthesis. For proper phonetics, esthetic and comfort there should be minimum amount of separation between the incisal edges of upper and lower anterior teeth during speech. The present study shows that there is no significant variation in closest speaking space amongst different age groups of both sexes and between sibilants. However, there is a significant difference in closest speaking space amongst individuals.

Oral lesions in relation to prosthetics. A review.

The oral mucosa is not designed to provide a foundation for denture base and is called upon to function in a new environment. Although dentures are fabricated for the purpose of improving health and well being of the patient, they may occasionally become injurious to oral tissues. Dentures are worn because of their essential role in appearance, in speech and mastication far outweighs their potential for damage. A thorough knowledge of the histologic features of the structures that support dentures is necessary for proper denture service. Various pathologic lesions that can occur following use of dentures are reviewed in this article.

Serotonergic modulation of spinal cord sympathetic preganglionic neurone activity in cardiovascular regulation.

The present study demonstrates the effect of activation of spinal serotonergic receptors on heart rate, blood pressure and cardiac arrhythmia induced by coronary artery ligation in cervical spinal cord transected and bilaterally vagotomized dogs. Intrathecal injection of serotonin (5-HT) evoked a fall in blood pressure (mean decrease, 16 +/- 3) and a decrease in heart rate (mean change, 24 +/- 6) and these effects were blocked by intrathecal pretreatment with methysergide. The magnitude of ventricular ectopics evoked by coronary artery ligation was decreased by serotonin (mean decrease, 31 +/- 5%), and this effect of serotonin was blocked by methysergide pretreatment intrathecally (mean change, 7 +/- 5%). Methysergide per se, increased the magnitude of ventricular ectopics (mean increase, 24 +/- 5%). The serotonergic receptors of the spinal cord appear to have an inhibitory influence on the cardiovascular functions.

Role of endogenous opioids and histamine in morphine induced emesis.

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.