Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

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.

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), ß-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.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Blood group discrepancy in Ah para-Bombay phenotype: a rare blood group variant and its clinical significance.

Individuals with the rare para-Bombay phenotype have inherited defects in producing H associated with FUT1 and/or FUT2 genes. We report a case of blood group discrepancy in a para-Bombay patient from a tertiary care hospital of eastern India. A 31-year-old woman with rheumatic heart disease presented with fatigue and breathlessness and was then scheduled for valvuloplasty, for which a blood transfusion request was sent to the blood center. During pre-transfusion testing, red blood cell (RBC) testing showed group O, and serum testing showed strong reactivity with group B RBCs, weak reactivity with group O RBCs, and very weak reactivity with group A RBCs. Saliva inhibition testing and enzyme treatment of RBCs concluded the patient to be of "Ah para-Bombay" phenotype. The patient's Lewis phenotype was Le(a-b+). This patient's serum also had cold-reacting anti-IH along with anti-B. This case report highlights the importance of performing an advanced immunohematologic workup, including adsorption, elution, enzyme treatment, and saliva inhibition testing for identification of weak A or B subgroups as well as the rare para-Bombay blood group, when routine ABO typing, using forward and reverse grouping, is inconclusive. Accurate identification of blood group helps in preventing transfusion-related adverse events and encouraging safe transfusion practice.Individuals with the rare para-Bombay phenotype have inherited defects in producing H associated with FUT1 and/or FUT2 genes. We report a case of blood group discrepancy in a para-Bombay patient from a tertiary care hospital of eastern India. A 31-year-old woman with rheumatic heart disease presented with fatigue and breathlessness and was then scheduled for valvuloplasty, for which a blood transfusion request was sent to the blood center. During pre-transfusion testing, red blood cell (RBC) testing showed group O, and serum testing showed strong reactivity with group B RBCs, weak reactivity with group O RBCs, and very weak reactivity with group A RBCs. Saliva inhibition testing and enzyme treatment of RBCs concluded the patient to be of "Ah para-Bombay" phenotype. The patient's Lewis phenotype was Le(a­b+). This patient's serum also had cold-reacting anti-IH along with anti-B. This case report highlights the importance of performing an advanced immunohematologic workup, including adsorption, elution, enzyme treatment, and saliva inhibition testing for identification of weak A or B subgroups as well as the rare para-Bombay blood group, when routine ABO typing, using forward and reverse grouping, is inconclusive. Accurate identification of blood group helps in preventing transfusion-related adverse events and encouraging safe transfusion practice.

Hypertension in Young Adults in India: Perspectives and Therapeutic Options amongst Clinician's in a Cross Sectional Observational Study.

BACKGROUND: The prevalence of hypertension in the young adult population is rising in India. Increased arterial stiffness due to RAAS activation and increased sympathetic overactivity due to stress have been implicated as primary factors for the same. This study was aimed to understand the Indian clinician's perspective on approach to management of hypertension in young adults. METHODS: A cross sectional observational survey using a structured questionnaire was conducted online with 2287clinicians (cardiologists, diabetologists, consultant physicians and family physicians). RESULTS: The prevalence of hypertension was 10-30% as per opinion of 64.8% clinicians. The top three risk factors for hypertension in young were perceived to be smoking, mental stress and obesity. Around 57.4% respondents opined that both increased heart rate and systolic blood pressure were markers of sympathetic overactivity. More than 60% respondents across specialities preferred ARBs to treat hypertension in young adults. Amongst the ARBs, telmisartan was the preferred ARB by >80% respondents. Metoprolol was the preferred beta blocker by almost 64% respondents. The objective of selection of beta-blocker by majority of clinicians due to sympathetic overactivity. Telmisartan and Metoprolol single pill combination achieved the BP goal in 40-60% of patients as reported by 41.3% of the physicians. The combination therapy was well tolerated in young hypertensive patients. CONCLUSIONS: Initiation of an early and appropriate antihypertensive treatment in young population may lower the burden of cardiovascular disease in this population. ARBs and beta -blockers were the preferred class of anti-hypertensive drugs in the cohort of young hypertensive patients .

Carcinoma-associated fibroblasts, its implication in head and neck squamous cell carcinoma: a mini review.

The communication between tumor stromal and parenchymal cells provides an insight to tumor progression. One of the main elements of the stroma, a major contributor to the extracellular environment of tumors, is carcinoma-associated fibroblasts. They can originate from either normal fibroblasts in the immediate vicinity of the tumor or from circulating bone marrow-derived mesenchymal stem cells. These myofibroblasts can arise locally from an endothelial-mesenchymal transformation at the invasive edge of the cancer and are physically associated with carcinoma cells, that is, in the development of high-grade malignancies and poor prognosis. These carcinoma-associated fibroblasts feed the epithelial tumor cells in a host-parasite relationship establishing its role in head and neck squamous cell carcinoma progression.

Clinical characteristics and 30-day outcomes in patients with acute decompensated heart failure: Results from Indian College of Cardiology National Heart Failure Registry (ICCNHFR).

BACKGROUND: Acute decompensated heart failure (ADHF) is a challenging medical emergency with high mortality and its prevalence is increasing in India. There is paucity of data on ADHF in the country. METHODS: Indian College of Cardiology National Heart Failure Registry (ICCNHFR) is an on-going observational registry on ADHF contributed by 22 hospitals across India; and we present the in-hospital and 30-day outcomes of ADHF patients enrolled from August 2018 to July 2019. Major objective included capturing demographics, comorbid conditions, aetiology, prescription patterns and assessing clinical outcomes. RESULTS: Of 5269 patients (mean age: 61.90 ± 13.85 years) enrolled in this study, males were predominant (67.09%). Mean duration of hospitalization was 5.74 ± 4.74 days. Ischemic heart disease was the most common (75.44%) aetiology. Abnormal electrocardiogram readings were found in most patients (89.86%). LVEF of ˂40% was found in 68.29% of patients. In-hospital mortality rates were 6.98%. The 30-day cumulative mortality was 12.35% and 30-day rehospitalization rate was 7.98%. At discharge, all guideline-based medical therapy (GDMT) were prescribed only to 24.99% of patients and 23.72% adhered to the prescription until 30 days. Older age, high serum creatinine levels and poor LVEF contributed to high mortality and rehospitalization. CONCLUSION: Patients with ADHF were younger and predominantly males. Usage of GDMT in ADHF patients was low (24.99%) and the in-hospital mortality was high. Older age, high serum creatinine levels, poor LVEF contributed for 30-day mortality and rehospitalization. This data on ADHF, could help in developing strategies to improve outcomes for HF patients in India.

Incidence and risk predictors analysis of adverse donor reactions in whole blood donation.

OBJECTIVE: Adverse donor reactions in normal healthy blood donors is not unusual. However, these unpleasant effects have a negative impact on donor retention. Adverse event due to blood donation is multifactorial in origin. Therefore, the objective of this study was to determine the frequency and type of adverse donor reactions during or after blood donation. More importantly, this study also aimed at analyzing important risk predictors of adverse donor reaction. MATERIAL AND METHODS: This was a retrospective study conducted from May 2017 to April 2019 in the department of Transfusion Medicine at a tertiary care center in eastern India. Data were stored in Microsoft excel 2016 by using a standardized format as per ISBT criteria and analyzed with software "R, version 3.5.3" to find out the various independent precipitating factor. RESULTS: Overall, 107 donors (0.98%) experienced adverse events with 10,814 whole blood donations. The first time, females, younger age donors (18-30 years), and donors with a mean arterial blood pressure of less than 90mm of Hg were the most important independent risk factors predicting the possibility of adverse donor reaction. Donors' weight, hemoglobin, and the type of donation had not affected the frequency of adverse events. CONCLUSION: Analysis of adverse donor reactions helps in selecting the blood donors who are at risk of donor reactions. Our study highlights the importance of proper predonation screening especially in terms of assessment of mean blood pressure, along with identification of first time and female blood donors in order to reduce untoward donor reaction.

Impact of the 2017 ACC/AHA guidelines on the prevalence of hypertension among Indian adults: Results from a cross-sectional survey.

BACKGROUND: The impact of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for diagnosis and management of hypertension on the prevalence of hypertension in India is unknown. METHODS: We analyzed data from the Cardiac Prevent 2015 survey to estimate the change in the prevalence of hypertension. The JNC8 guidelines defined hypertension as a systolic blood pressure of ≥140 â€‹mmHg or diastolic blood pressure of ≥90 â€‹mmHg. The 2017 ACC/AHA guidelines define hypertension as a systolic blood pressure of ≥130 â€‹mmHg or diastolic blood pressure of ≥80 â€‹mmHg. We standardized the prevalence as per the 2011 census population of India. We also calculated the prevalence as per the World Health Organization (WHO) World Standard Population (2000-2025). RESULTS: Among 180,335 participants (33.2% women), the mean age was 40.6 â€‹± â€‹14.9 years (41.1 â€‹± â€‹15.0 and 39.7 â€‹± â€‹14.7 years in men and women, respectively). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%) and 2,878 (1.6%) participants belonged to age group 18-19, 20-44, 45-54, 55-64, 65-74 and â€‹≥ â€‹75 years respectively. The prevalence of hypertension according to the JNC8 and 2017 ACC/AHA guidelines was 29.7% and 63.8%, respectively- an increase of 115%. With the 2011 census population of India, this suggests that currently, 486 million Indian adults have hypertension according to the 2017 ACC/AHA guidelines, an addition of 260 million as compared to the JNC8 guidelines. CONCLUSION: According to the 2017 ACC/AHA guidelines, 3 in every 5 Indian adults have hypertension.

Prevalence of hypertension among Indian adults: Results from the great India blood pressure survey.

OBJECTIVE: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults. METHODS: A national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India. RESULTS: Blood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18-19, 20-44, 45-54, 55-64, 65-74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively. CONCLUSION: There is a high prevalence of hypertension, with almost one in every three Indian adult affected.

Peripartum cardiomyopathy.

OBJECTIVE: To determine the clinical and echocardiographic profiles of women with peripartum cardiomyopathy and ascertain the natural course of the disease. METHODS: Fifty-six women with peripartum cardiomyopathy were followed up for a mean period of 6.1 years and their clinical and echocardiographic profiles were studied as well as their outcomes. RESULTS: The mean+/-SD age at presentation was 31+/-5 years and mean parity was 2.6+/-1. Of the 56 patients, 18 (32.1%) had NYHA Class II, 24 (42.9%) had NYHA Class III, and 14 (25%) had NYHA Class IV symptoms, and 21 (37.5%) and 35 (62.5%), respectively, presented with features of heart failure during pregnancy and the postpartum. During follow-up, the left ventricular ejection fraction improved from 31%+/-7.2% to 43%+/-8% (P

Left ventricular dysfunction in patients with subclinical hypothyroidism and its reversibility after hormone therapy.

AIM: To ascertain the presence of LV dysfunction in patients of subclinical hypothyroidism and its reversibility after hormone therapy. METHODS AND METERIAL: Thirty two patients with subclinical hypothyroidism (SH) were included in the study, along with thirty two age and sex matched individuals serving as controls. The patients with SH had normal serum T3 and T4 with an elevated TSH value. All patients and the controls were subjected to detailed echocardiographic examination for assessment of LV systolic and diastolic function before and one year after hormone (thyroxine) therapy. RESULTS: The systolic function of LV was normal in patients with SH. There was significant diastolic dysfunction in the SH patients as compared with controls. There was prolongation of deceleration above time (169 +/- 6.1 msec. vs. 148.1 +/- 5.4 msec in controls, p < 0.05), isovolumic relaxation time (89.1 +/- 7.3 msec vs. 79.4 +/- 5.9 msec., p<0.05), increased A wave (0.63 +/- 0.6 m/sec. vs. 0.54 +/- 0.05 m/sec) and reduced E/A ratio (0.7 +/- 0.09 vs. 1.4 +/- 0.3, p < 0.05). Echocardiography at the end of one year of hormone therapy revealed considerable improvement in diastolic function of the LV. There was significant improvement in DT (from 169 +/- 6.1 msec. to 151 +/- 5.2 msec, p < 0.05), IVRT (from 89.1 +/- 7.3 msec. to 80.2 +/- 6.5 msec, p < 0.05) and increased E/A ratio (from 0.7 +/- 0.09 to 1.3 +/- 0.1, p < 0.05). CONCLUSION: Hypothyroidism, even in subclinical stage, can cause diastolic dysfunction of the LV. These abnormalities in diastolic function can be reversed by thyroxine therapy.

Balloon mitral valvuloplasty during pregnancy.

OBJECTIVES: Balloon mitral valvuloplasty (BMV) has been performed safely during pregnancy with good results. Reports are few on long-term effects of BMV on childhood development. METHODS: BMV was performed in 40 pregnant women (age 23.4+/-4.8 years) with severe mitral stenosis at 24.2+/-4.6 weeks of gestation. RESULTS: Mitral valve area increased from 0.82+/-0.34 to 1.9+/-0.4 cm(2) (P<0.001). One patient had pericardial tamponade. Mean fluoroscopy time was 5.5+/-3.8 min. There was no maternal death, no abortion, no intrauterine growth restriction and one stillbirth. All 39 babies were normal at birth. One baby died at 7 months due to pneumonia. On follow up for 36+/-15 months, all 38 babies maintained normal growth and development without any thyroid disease or malignancy. CONCLUSIONS: During pregnancy BMV is feasible, safe and effective. Maternal and fetal outcomes are excellent. Growth and milestone of development are not affected.

Percutaneous balloon angioplasty of membranous obstruction of the inferior vena cava.

BACKGROUND: Membranous obstruction of the inferior vena cava is common in African and Asian countries. METHODS AND RESULTS: Between January 1999 and January 2002, 19 patients were prospectively studied. The mean age of the patients was 38+/-6.9 years. All of them had swelling of the abdomen and ankle edema. Five patients (26.3%) had jaundice, 9 (47.3%) had hepatomegaly, and 5 (26.3%) splenomegaly. Ultrasonography could detect the site of obstruction in 18 patients (94.7%). Vena cavography demonstrated obstruction of the inferior vena cava at the level of the diaphragm, with 2 patients (10.5%) having additional intrahepatic obstruction. The mean pressure gradient was 22+/-3.5 mmHg. Seventeen patients underwent balloon angioplasty using a Joseph balloon. The procedure was successful in 15 patients (88.2%). The post-angioplasty mean pressure gradient was 5+/-1.4 mmHg. On follow-up, 3 patients (20%) developed features of restenosis: out of them, 2 underwent successful redilatation. CONCLUSIONS: Balloon angioplasty of membranous obstruction of the inferior vena cava is feasible with a high success rate, without any rupture of the inferior vena cava.

Has the prevalence of rheumatic fever/rheumatic heart disease really changed? A hospital-based study.

BACKGROUND: Rheumatic fever and rheumatic heart disease still remain major public health problems. With a dramatic rise in the incidence of coronary artery disease cases, the focus of the physician seems to be shifting away from rheumatic fever and rheumatic heart disease. The aim of the present study was to assess the prevalence of rheumatic fever and rheumatic heart disease, and to ascertain if there was any decline in the prevalence of the disease. For the first time, data on the prevalence of rheumatic fever and rheumatic heart disease are reported from Orissa, an underdeveloped state in eastern India. METHODS AND RESULTS: We scrutinized the records of cardiac patients admitted to the medicine, pediatrics and cardiology wards of the SCB Medical College and Hospital, Cuttack from 1981 to 1990 and 1991 to 2000. During the period 1981-1990, out of 11,782 cardiac patients, 5537 (46.9%) were suffering from rheumatic fever and rheumatic heart disease. During 1991-2000, out of 14,803 cardiac patients, 6670 hospitalized patients (45%) were found to have rheumatic fever and rheumatic heart disease. During the first and second periods, the number of patients with rheumatic fever admitted was 1079 (9.2%) and 1330 (8.9%), respectively. The decline in the percentage of rheumatic fever cases was statistically not significant (p>0.05). During the two periods, the number of rheumatic heart disease patients admitted was 4458 (37.8%) and 5340 (36.1%), respectively. During both the periods studied, the decline in the percentage of rheumatic heart disease cases admitted was statistically not significant (p>0.05). We also compared rheumatic fever and rheumatic heart disease cases admitted during 1981-1985 with those admitted during 1996-2000. This analysis also did not show any demonstrable decline in the prevalence of the disease (2692 [46.2%] v. 3296 [44.4%], p>0.05). CONCLUSIONS: Our results show that rheumatic fever and rheumatic heart disease cases constitute a significant percentage of the admissions of total cardiac cases to our hospital. Over the past 20 years, there is no significant decline in the percentage of rheumatic fever and rheumatic heart disease cases being admitted to a major government hospital.

Myocarditis as an initial manifestation of systemic lupus erythematosus.

We report a case of systemic lupus erythematosus (SLE) whose initial presentation was in the form of myocarditis. The patient did not have arthritis, fever or butterfly rash. Presence of LE cell phenomenon, positive ANA, anti-DS DNA antibodies, leucopenia and high ESR with polyserositis indicated the diagnosis to be SLE. Therapy with steroid resulted in complete recovery. The patient developed atrial fibrillation during her course of acute illness which is being reported for the first time.