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.

Seasonal Variation in Arterial Blood Pressure.

Background: There is need to evaluate influence of weather changes on blood pressure in human population that has often been ignored in clinical practice guidelines. Objectives: Present study was planned to find the seasonal variation of blood pressure. Methods: Seasonal variation in blood pressure was examined in 1081 participants of age 18 years and over from both genders, 540 from rural and 541 from urban practice area of Department of Community Medicine of tertiary care teaching hospital of Ludhiana. Information was obtained on demographic and socioeconomic characteristics and socio-economic status followed by clinical examination. Anthropometric measurements included weight, height, waist circumference, hip circumference, waist and hip ratio, Body Mass Index. Blood pressure was recorded and classified based on JNC VII criteria. Data was obtained on four different seasons (winter, summer, monsoon and post-monsoon) as defined by Indian meteorological department. Results: Present study showed that there is significant increase in the blood pressure in study population during winter and significant fall in summer in both systolic (SBP) and diastolic blood pressures (DBP) irrespective of age, sex, socioeconomic status, occupation. The variation in SBP between summer and winter season was maintained across all the age groups except in elderly where maximal difference was observed in monsoon - summer seasons. Mean SBP and DBP were higher in 41 to 50 years and more than 60 year age group; females have a higher increase in both mean SBP and DBP. Advancement in age and females gender confirmed more significant changes in blood pressure across ambient temperatures. Conclusion: Our study showed that climatic changes influence the blood pressure recordings and should also be considered for management of hypertension.

Clinical and angiographic profile of patients presenting with first acute myocardial infarction in a tertiary care center in northern India.

OBJECTIVE: Acute myocardial infarction (AMI) is one of the presentation of coronary artery disease (CAD) and is thought to occur in younger age group in this region. The objective of this study was to evaluate clinical, biochemical and angiographic profile of patients with first acute myocardial infarction. METHODS: Eight hundred and forty-six consecutive patients who underwent coronary angiography within 4 weeks of MI were included. RESULTS: Males (n = 705, 83.3%) outnumbered females (n = 141, 16.7%) in each age group. Mean age of presentation was lower in females (58.25 +/- 9.69: 55.74 +/- 10.63). Three hundred and forty-two (40.8%) patients were thrombolyzed. Most common type of MI was anterior wall MI (n = 485, 57.32%). Three hundred and forty (40.4%) were diabetic with females outnumbering males proportionately (females = 63, 44.68%: males = 277, 39.29%). More females were hypertensive (females = 81, 57.45%: males = 306, 43.40%). Prevalence of smoking was quite low (n = 140, 16.50%) and mean age of smokers was less by 7 years than non-smokers. One hundred and forty-two (16.7%) were obese with mean age of presentation less by 7 years than non-obese. Single vessel disease (SVD) was more prevalent (361/846; 42.67%) and was more common in younger, non-diabetics and smokers. Diabetics were more likely to have triple vessel disease (TVD) (n = 112, 32.95%). CONCLUSIONS: The study reveals that age of first AMI was comparable to that in western world. Females tend to be more hypertensive and diabetics. Younger, non-diabetics and smokers tend to have single-vessel disease. Diabetics and older population were more likely to have diffuse disease (TVD).

Gastrointestinal bleed after leeching in a patient on aspirin therapy.

Leeches ( Hirudo medicinalis ) have been used in health care for their property of bloodletting. Bleed occurring from the site of leech attachment has been well documented. We report a 50-year-old man who was on aspirin therapy for coronary artery disease, and presented with GI bleed after leech treatment for his knee pain.

Prevalence of sustained hypertension and obesity in urban and rural school going children in Ludhiana.

BACKGROUND: Increasing trend of hypertension is a worldwide phenomenon. The data on sustained hypertension in school going children is scanty in India. The present study was conducted to evaluate the prevalence of sustained hypertension and obesity in apparently healthy school children in rural and urban areas of Ludhiana using standard criteria. METHODS AND RESULTS: A total of 2467 apparently healthy adolescent school children aged between 11-17 years from urban area and 859 students from rural area were taken as subjects. Out of total 3326 students, 189 were found to have sustained hypertension; in urban areas prevalence of sustained hypertension was 6.69% (n=165) and in rural area it was 2.56% (n=24). Males outnumbered females in both rural and urban areas. The mean systolic and diastolic blood pressure of hypertensive population in both urban and rural population was significantly higher than systolic and diastolic blood pressure in their normotensive counterparts (urban normotensive systolic blood pressure:115.48+/-22.74 mmHg, urban hypertensive systolic blood pressure: 137.59+/-11.91 mmHg, rural normotensive systolic blood pressure: 106.31+/-19.86 mmHg, rural hypertensive systolic blood pressure: 131.63+/-10.13 mmHg, urban normotensive diastolic blood pressure: 74.18+/-17.41 mmHg, urban hypertensive diastolic blood pressure: 84.58+/-8.14 mmHg, rural normotensive diastolic blood pressure: 68.84+/-16.96 mmHg, rural hypertensive diastolic blood pressure: 79.15+/-7.41 mmHg). Overweight populationwas significantly higher in urban area. There were 287 (11.63%) overweight students and 58 (2.35%) were obese. In rural population overweight and obese students were 44 (4.7%) and 34 (3.63%) respectively. There was significant increase in prevalence of hypertension in both rural and urban population with increased body mass index in urban students; those with normal body mass index had prevalence of hypertension of 4.52% (n=96), in overweight it was 15.33% (n=44) and in obese it was 43.10% (n=25). In rural area, the overweight students showed prevalence of sustained hypertension in 6.82% (n=3) and in obese group it was 61.76% (n=21). None of the student with normal body mass index in rural area was found to be hypertensive. The mean body mass index of hypertensive population in both rural and urban areas was significantly higher than respective normotensive population (mean body mass index in urban normotensive group: 20.34+/-3.72 kg/m2, hypertensive group: 24.91+/-4.92 kg/m2; mean body mass index in rural normotensive group: 18.41+/-3.41 kg/m2, hypertensive group: 21.37+/-3.71 kg/m2, p<0.01). CONCLUSIONS: Prevalence of sustained hypertension is on the rise in urban area even in younger age groups. Blood pressure is frequently elevated in obese children as compared to lean subjects. This is possibly related to their sedentary lifestyle, altered eating habits, increased fat content of diet and decreased physical activities.

Validation of tobacco and alcohol intake questionnaire in relation to food intakes for the Five City Study and a proposed classification for Indians.

Cross-sectional survey was conducted among 1806 subjects (904 men and 902 women) between 25-64 years of age. The survey instruments were questionnaires according to guidelines of WHO and other Indian studies and based on scores of various attributes of tobacco and alcohol consumption. All subjects with tobacco and alcohol consumption were classified separately into mild, moderate and heavy consumption and previous consumptions were also recorded. The overall prevalence of tobacco consumption was significantly higher in men compared to women (27.5 vs 11.6%), while mild tobacco intakes were comparable (2.0 vs 1.6%), moderate (22.2 vs 7.7%) and heavy (3.3 vs 2.2%) tobacco consumptions were significantly higher in men compared to women. The overall prevalence of alcohol consumption was 10.4% in men without any subject among women. The prevalence of moderate (6.6%) alcohol intakes was significantly higher compared to mild (1.2%) and heavy (2.5%) alcohol consumption. Whisky and country liquor were most commonly consumed alcoholic beverages. Smoking (20.7 vs 1.6%) and tobacco chewing (13.3 vs 10.7%) in men and women respectively were common modes of tobacco consumption. Tobacco consumption was significantly associated with lower consumption of vitamin C and beta-carotene and lower body mass index. These findings suggest that tobacco and alcohol consumption assessed by scores constructed on the basis of various attributes appear to be accurate and the questionnaires may be used with precision for classification and assessment in other population groups.

Should beta-blockers be withdrawn in post-myocardial infarction patients before treadmill test?

In most patients of myocardial infarction, beta-blockers are used for secondary prophylaxis and a treadmill test is required for risk stratification. To study the effect of oral beta-blockers on interpretation of treadmill test, 54 consecutive patients were subjected to treadmill test four to six weeks after myocardial infarction. Fourteen patients with strongly positive treadmill test were referred for coronary angiography. Treadmill test was repeated in 37 patients 72 hours after withdrawal of beta-blockers. The peak exercise heart rate was significantly different while off and on beta-blockers (148 +/- 13 bpm vs 124 +/- 14 bpm, respectively; p < 0.01). The test was negative on both the occasions in 17 patients. On stopping beta-blockers, the negative test became mildly positive in five and strongly positive in six patients. The mildly positive test became strongly positive in four patients and remained almost unchanged in five. In 10 patients there was conversion of negative or mildly positive treadmill test into strongly positive result after withdrawal of beta-blockers. Thus the risk stratification changed significantly in 27 percent patients. It is suggested that beta-blockers can and should be withdrawn in post-MI patients before doing treadmill test.

Evaluation of serum lipid profile and cardiac enzyme changes in cerebrovascular accidents.

Serum lipid profile is, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides and serum cardiac enzymes ie, creatinine phosphokinase (CPK), creatinine phosphokinase isoenzyme MB (CPK-MB), lactate dehydrogenase (LDH) and serum aspartate aminotransferase (AST/SGOT) levels were estimated in 50 cases of cerebrovascular accidents (CVA) consisting of 26 cases of cerebral haemorrhage and 24 cases of cerebral thrombosis. All analyses were made on day 1 and day 7. Serum cholesterol, LDL and triglycerides levels were significantly higher in CVA patients on day 1. Lipid level fell significantly on day 7 in respect to day 1. On comparing the lipid levels between cerebral haemorrhage and cerebral thrombosis, no significant difference was observed. Cardiac enzymes like CPK and CPK-MB were significantly raised whereas, AST/SGOT and LDH were marginally raised on day 1 in CVA patients. However, there was no change in cardiac enzyme levels between cerebral haemorrhage and cerebral thrombosis patients.

Epidemiology of coronary heart disease in a rural Punjab population--prevalence and correlation with various risk factors.

An epidemiological study to find out the prevalence of coronary heart disease (CHD) and the influence of risk factors on the prevalence of CHD in a total rural community of Punjab was conducted in Pohir, situated near Ludhiana. A total of 1100 individuals (623 males and 477 females) out of a possible 1617 individuals (> 30 yrs) living in 3 villages were studied. In each case a detailed history, physical examination and a 12 lead electrocardiogram (ECG) were recorded. Samples for blood sugar and serum cholesterol were taken. By Epstein's criteria of ECG (using the Minnesota coding), the prevalence of CHD was 30.8/1000, being higher in women (37.7/1000) than in men (25.6/1000). By a clinical judgement method considering history, ECG and treadmill testing (TMT) collectively, prevalence was 31.8/1000, being still higher in women (33.5/1000) than in men (30.5/1000). The prevalence of various risk factors like hypertension, smoking, hypercholesterolemia and diabetes was found to be 14.5%, 8.9%, 7.0% and 4.6% respectively. Of the various risk factors tested, hypertension, hypercholesterolemia and a positive family history showed an association with CHD. Only 38% of patients with CHD, 37% of the hypertensives and 52% of the diabetics were aware of its presence. The knowledge in the general population about risk factors causing CHD is poor.

Effect of posture in immediate post-exercise period on ischaemic ST-changes during stress electrocardiographic testing.

In this study of stress testing, the posture in which patients were put had effect on heart rate, blood pressure, rate pressure product and ST-segment depression integral in the recovery phase. The systolic blood pressure in recovery phase of stress testing fell more rapidly towards normal pre-exercise value in sitting (Group I) than in lying down (Group II) posture (p < 0.05) from 2nd to 5th minute. The changes in heart rate were less and slower in lying posture than with sitting up. The decrease in rate pressure product (RPP), a determinant of myocardial oxygen requirement was lower in lying down than in sitting up posture (p < 0.05) from 2nd to 5th minute of recovery. Consequently, ST-depression, a marker of ischaemia was more marked in lying down than sitting up. The ST-depression integral was 4.15 +/- 1.2 and 7.10 +/- 1.65 in 2nd minute in group I and group II respectively, and the difference was statistically significant in 2nd, 7th (p < 0.05) and 8th minute (p < 0.01) of recovery. These changes are important in interpretation of results of exercise testing.

Holter monitoring in chronic renal failure before & during dialysis.

Holter monitoring was done prospectively in 50 adult patients of chronic renal failure (CRF) before and during haemodialysis. Frequent premature ventricular contractions (PVC's) were present in 3 (6%), all during dialysis (Gp I). Sporadic PVC's were seen in 6 (12%) and rest 41 (82%) had no PVC (Gp II). Premature atrial contractions (PAC's) were frequent in 5 (10%) (one had precipitation during dialysis), sporadic in 7 (14%) and none in 38 (76%). Ventricular tachycardia (VT) was not seen. Supraventricular tachycardia (SVT) was observed in 5. No biochemical parameter correlated with arrhythmias. There was no correlation between hypotension episodes and arrhythmias. Sinus tachycardia occurred during the third and fourth hours of dialysis. This correlated with hypotensive episodes observed in 13 patients. Episodes of silent myocardial ischaemia (SMI) observed in 12 patients occurred predominantly during this period of tachycardia. Cardiac arrhythmias are infrequent in CRF and are mainly seen in patients with preexisting coronary artery disease with low ejection fractions (EF) (EF 0.37 +/- 0.2 in Gp I and 0.80 +/- 0.1 in Gp II P < 0.01) and abnormal Q waves in baseline ECG. They do not seem to contribute to occurrence of episodes of dialysis induced hypotension.

Feasibility of thrombolytic therapy--a one year prospective study.

A one year prospective study was conducted on all the patients admitted with clinical diagnosis of acute myocardial infarction (AMI) to determine the proportion of patients who can be given thrombolytic therapy. Factors responsible for non-administration were analysed. 213 patients with AMI entered the study. Standard inclusion criteria for thrombolytic therapy were used. 101 (47%) patients failed to meet the inclusion criteria. This included 7 (3.3%) who failed to satisfy the electrocardiographic (ECG) criteria. Nine patients with atypical symptoms were unable to reach within the stipulated 6 hours while the remaining 85 (40%) patients were delayed inspite of typical features due to inability of the patient to attribute the symptoms to the heart, lack of proper transport facility and self medication. 112 patients (53%) met the inclusion criteria but 7 patients were excluded because of age (> 70 years), and another 8 because of contraindications. Of the remaining 97 patients, 47 failed to receive thrombolytic therapy due to lack of awareness of the benefits of thrombolytic therapy by the first treating physician, misinterpretation of ECG, inability to afford and refusal to give consent. Only 50 patients (23%) received thrombolytic therapy. This low figure can be easily improved upon by the correction of a number of remediable factors.