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.

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.

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.

COVID-Inflicted Coagulopathy: Expert Consensus on Management with Novel Oral Anticoagulants in India.

Coronavirus disease 2019 (COVID-19) is a highly hypercoagulable viral infection complicated as COVID-inflicted coagulopathy (CIC), that is associated with increased risk of morbidity and mortality. International guidelines recommend low molecular weight heparin (LMWH) to treat CIC in both in-hospital and in-home settings. However, in India, using subcutaneous LMWH may not be a feasible option for a vast majority of patients under home management. Additionally, while some evidence advocates the use of novel oral anticoagulants (NOACs), in hospitalized settings, most guidelines find no role of NOACs in hospital settings. On the other hand, the resource crunch faced in recent COVID-19 pandemic in India forced physicians to treat many patients in home settings. These patients had been usually prescribed NOACs for ease of administration and adherence. Therefore, there is a need to form a consensus on the use of NOACs to manage CIC in India.

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 .

Expert Opinion on P2Y12 Inhibitors Use in Management of Acute Coronary Syndromes: Focus on Ticagrelor.

Ticagrelor is a potent, oral P2Y12 inhibitor used as a part of dual antiplatelet therapy (DAPT) in acute coronary syndromes (ACS). New evidence has emerged for its use in ACS, which may be crucial for the Indian context. This brought together nearly 150 experts in ACS management across the country who reviewed the current evidence and discussed the same through a series of 10 meetings on an online platform. With all experts' agreement, the key expert opinions for the P2Y12 inhibitors use in ACS management were finalized. These include the following. In ACS patients aged <75 years, with diabetes, a history of stroke/transient ischemic attack, and chronic kidney disease, ticagrelor may be preferred over other P2Y12 inhibitors. It may also be preferred in the elderly above 75 years with clopidogrel is a suitable alternative in patients at high-risk of bleeding. Rates of stent thrombosis are lower with ticagrelor than clopidogrel. In patients managed with fibrinolysis, use ticagrelor after 48 hours if streptokinase was the fibrinolytic agent or it can be used after 12 to 24 hours if fibrin-specific fibrinolytic was used. Rates of major bleeding in patients treated with fibrinolysis are similar to clopidogrel. Prehospital administration may be preferred over in-hospital administration with expected bleeding rates similar to clopidogrel. Switching among P2Y12 inhibitors should be done with due consideration of their pharmacodynamics. At present, DAPT should be continued for 12 months with discontinuation after three to six months in patients with high bleeding risk. The use of low dose ticagrelor may be considered in cases with high-bleeding risk. DAPT or ticagrelor continuation beyond one year should be individualized considering ischemic and bleeding risks. Dyspnea is a common, mild, and transient and does not necessitate ticagrelor discontinuation. Severe dyspnea should be investigated thoroughly. In conclusion, ticagrelor (180 mg, 90 mg, and 60 mg doses), a potent antiplatelet is expected to reshape the antiplatelet use in the management of ACS.

Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population.

WHAT IS KNOWN AND OBJECTIVE: Statins form the backbone of lipid-lowering therapy for the prevention of cardiovascular disease. However, there is large interindividual variability in clinical response to statin treatment. Several gene variants that can be aligned to either the pharmacokinetics or pharmacodynamics of statin have been proposed as potentially important determinants of statin response. We aimed to study the association of known variations in SLCO1B1, CYP3A4, ABCB1, CYP3A5, ABCG5 and CYP7A1 genes with lipid levels in response to atorvastatin therapy. METHODS: Genotypes were determined using multiplex allele-specific polymerase chain reaction in 177 Indian patients, treated with 10 mg of atorvastatin for 8 weeks. Low-density lipoprotein-cholesterol (LDL-C) levels were recorded at baseline and after 8 weeks of atorvastatin treatment. RESULTS AND DISCUSSION: A total of 177 hypercholesterolaemic patients were genotyped to study genetic determinants of atorvastatin response. The genotype distribution for all polymorphisms investigated was in Hardy-Weinberg equilibrium. In our study, patients with wild-type genotypes of CYP7A1 (rs3808607), CYP3A4 (rs2740574), SLCO1B1 (rs2306283) and variant allele-carrying genotype of ABCB1 (rs2032582, rs1045642) showed significantly greater LDL-cholesterol reductions in response to atorvastatin therapy. WHAT IS NEW AND CONCLUSION: The variable response to atorvastatin therapy in terms of LDL-cholesterol lowering due to genetic variations in CYP7A1, CYP3A4, SLCO1B1 and ABCB1 is a promising finding. Further validation in large Indian cohorts is required before it can be assessed for clinical utility.

Expert Consensus on Ivabradine-based Therapy for Heart Rate Management in Chronic Coronary Syndrome and Heart Failure with Reduced Ejection Fraction in India.

Heart rate is an important indicator of health and disease and the modulation of heart rate can help to improve cardiovascular outcomes. Besides ß-blockers, Ivabradine is a wellestablished heart rate modulating drug that reduces heart rate without any hemodynamic effects. This consensus document was developed with the help of expert opinions from cardiologists across India on effective heart rate management in routine clinical practice and choosing an appropriate Ivabradine-based therapy considering the available scientific data and guideline recommendations. Based on the discussion during the meetings, increased heart rate was recognized as a significant predictor of adverse cardiovascular outcomes among patients with chronic coronary syndromes and heart failure with reduced ejection fraction making heart rate modulation important in these subsets. Ivabradine is indicated in the management of chronic coronary syndromes and heart failure with reduced ejection fraction for patients in whom heart rate targets cannot be achieved despite guideline-directed ß-blocker dosing or having contraindication/intolerance to ß-blockers. A prolonged release once-daily dosage of Ivabradine can be considered in patients already stabilized on Ivabradine twice-daily. Ivabradine/ß-blocker fixed-dose combination can also be considered to reduce pill burden. Two consensus algorithms have been developed for further guidance on the appropriate usage of Ivabradine-based therapies. Ivabradine and ß-blockers can provide more pronounced clinical improvement in most chronic coronary syndromes and heart failure with reduced ejection fraction patients with a fixed-dose combination providing an opportunity to improve adherence.

Usefulness of ambulatory blood pressure measurement for hypertension management in India: the India ABPM study.

The present paper reports differences between office blood pressure (BP) measurement (OBPM) and ambulatory blood pressure measurement (ABPM) in a large multi-centre Indian all comers' population visiting primary care physicians. ABPM and OBPM data from 27,472 subjects (aged 51 ± 14 years, males 68.2%, treated 45.5%) were analysed and compared. Patients were classified based on the following hypertension thresholds: systolic BP (SBP) ≥ 140 and/or diastolic BP (DBP) ≥90 mmHg for OBPM, and SBP ≥ 130 and/or DBP ≥ 80 mmHg for 24-h ABPM, and SBP ≥ 120 and/or DBP ≥ 70 mmHg for night-time ABPM and SBP ≥ 135 and/or DBP ≥ 85 mmHg for daytime ABPM, all together. White coat hypertension (WCH) was seen in 12.0% (n = 3304), masked hypertension (MH) in 19.3% (n = 5293) and 55.5% (n = 15,246) had sustained hypertension. Isolated night-time hypertension (INH) was diagnosed in 11.9% (n = 3256). Untreated subjects had MH relatively more often than treated subjects (23.0% vs. 14.8%, p < 0.0001; respectively). Females had higher relative risk (RR) of having WCH than males (RR 1.16 [CI 95, 1.07-1.25], p < 0.0001). Whereas, males had higher RR of MH than females (RR 1.09 [CI 95, 1.02-1.17] p < 0.01). INH subjects had lower average systolic and diastolic dipping percentages (0.7 ± 6.6/ 2.2 ± 7.9 vs. 9.0 ± 7.3/11.9 ± 8.5, p < 0.001) than those without INH. In conclusion, for diagnosis of hypertension there was a contradiction between OBPM and ABPM in approximately one-third of all patients, and a substantial number of patients had INH. Using ABPM in routine hypertension management can lead to a reduction in burden and associated costs for Indian healthcare.

Cardiological society of India document on safety measure during echo evaluation of cardiovascular disease in the time of COVID-19.

An echocardiographic investigation is one of the key modalities of diagnosis in cardiology. There has been a rising presence of cardiological comorbidities in patients positive for COVID-19. Hence, it is becoming extremely essential to look into the correct safety precautions, healthcare professionals must take while conducting an echo investigation. The decision matrix formulated for conducting an echocardiographic evaluation is based on presence or absence of cardiological comorbidity vis-à-vis positive, suspected or negative for COVID-19. The safety measures have been constructed keeping in mind the current safety precautions by WHO, CDC and MoHFW, India.

Hypereosinophilic syndrome with isolated Loeffler's endocarditis: complete resolution with corticosteroids.

Hypereosinophilic syndrome (HES) is classically defined as prolonged, unexplained peripheral eosinophilia in a patient presenting with evidence of end-organ damage. The heart is involved in two forms; endomyocardial fibrosis (Davies disease) and eosinophilic endocarditis (Loffler's endocarditis). It was first reported in 1968 by Hard and Anderson. Chusid and co-workers formulated a definition with strict criteria for the diagnosis of HES as 1) peripheral blood eosinophilia more than 1500 cells/cu mm for at least six months duration 2)signs, symptoms of end-organ (heart, lungs, gastrointestinal tract, skin, bone-marrow, brain) involvement with eosinophil tissue infiltration/injury 3) exclusion of known secondary causes of eosinophilia. We report a case of hypereosinophilic syndrome with Loffler's endocarditis, in the absence of endomyocardial fibrosis. The patient presented with a eosinophilic vegetation over the posterior leaflet of the mitral valve. There was complete resolution of the vegetation after two months of corticosteroid therapy.

Association between genetic loci linked to HDL-C levels and Indian patients with CAD: a pilot study.

OBJECTIVE: To examine the association between loci linked to high-density lipoprotein cholesterol (HDL-C) levels and coronary artery disease (CAD). METHODS: A pilot study consisting of age-matched and gender-matched angiographically confirmed CAD cases (n=150) and non-CAD controls (n=150) was performed to test an association. Illumina's Human Cardio-Metabo BeadChip containing 3112 variants associated with HDL-C levels was used for genotyping. RESULTS: A preliminary analysis identified 36 variants from 16 genes that were statistically significant (p<0.05) between cases and controls. However, none of the variants remained statistically significant after correction for multiple testing. Besides, variants rs11039159 (MADD), rs749067 (MADD), rs367070 (LILRA3) and rs330921 (PPP1R3B) showed modest association with HDL-C levels. CONCLUSIONS: None of the HDL-C associated loci included in this study were found to be a significant risk factor for CAD. However, the study could replicate the findings of four variants influencing HDL-C levels.

Time to shift from contemporary to high-sensitivity cardiac troponin in diagnosis of acute coronary syndromes.

Early rule-in and rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) is a challenge. In patients with inconclusive findings on ECG, cardiac biomarkers play a crucial role in the diagnosis. The introduction of the new high-sensitive cardiac troponin test (hs-TnI assay) has changed the landscape of NSTEMI diagnosis. The new hs-TnI assay can detect troponin values at a lower level compared with a contemporary cardiac troponin (cTn) assay. The hs-cTnI assay has a coefficient of variation of ≤10%, well below the 99th percentile value. It reduces the time to diagnose acute myocardial infarction from 6h to 3h. A recent study has demonstrated that hs-cTnI can further reduce the time to 1h in 70% of all patients with chest pain. The European Society of Cardiology 2015 guidelines recommend including a second sample of hs-cTnI within 3h of presentation This increases the sensitivity of the hs-TnI assay from 82.3% (at admission) to 98.2% and negative predictive value from 94.7% (at admission) to 99.4%. Combining the 99th percentile at admission with serial changes in troponin increases the positive predictive value to rule in acute coronary syndrome from 75.1% at admission to 95.8% after 3h. The 2015 ESC Guidelines recommend the use of a rapid rule out protocol (0h and 1h) when hs-cTnI with a validated 0 to1h algorithm is available. Training and displaying the clinical algorithm depicting the role of hs-TnI assay in acute cardiac care units and in EDs are an efficient way to deliver the new standard of care to patients. Compared with contemporary troponin assays, the hs-cTn assay accelerates the diagnostic pathway to 0-1h, thus reducing the time for diagnosis of NSTEMI and hence, its management.

Tachycardiac storm in infant with WPW syndrome: "rescue" radiofrequency ablation.

A two-month-old child having WPW syndrome and orthodromic tachycardia was on treatment with digoxin, flecainide and amiodarone. Despite this, he continued to have severe, very frequent episodes of tachycardia. The left-sided accessory pathway was hence ablated via a patent foramen ovale.