Indian Consensus on the Role and Position of Angiotensin Receptor-neprilysin Inhibitors in the Management of Heart Failure.

The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)].

Fixed-dose Combination of Torsemide and Mineralocorticoid Receptor Antagonists.

The combination of torsemide and spironolactone presents a promising approach to managing conditions such as edema and hypertension. Torsemide, a loop diuretic, enhances diuresis by inhibiting sodium reabsorption in the kidneys, while spironolactone, a potassium-sparing diuretic and mineralocorticoid receptor antagonist (MRA), complements this effect by preventing potassium loss and offering additional cardiovascular benefits. This review examines clinical evidence supporting their combined effectiveness in treating fluid retention and improving outcomes in conditions like heart failure (HF). Given the limited research available, it is essential to carefully evaluate patient-specific factors. However, several side effects necessitate careful patient selection and monitoring. Moreover, optimizing dosing regimens is crucial to ensure the safety and efficacy of torsemide and MRAs in clinical settings.

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.

The Promise of Cilnidipine in Hypertension with Comorbidities: National Consensus Statement: National Consensus Group Comprises Cardiologists, Nephrologists, and Diabetologists from India in a National Meet at New Delhi held on 22nd May 2022.

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.

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.

Burden of bradycardia and barriers to accessing bradycardia therapy in underserved countries.

Bradycardia, a condition characterized by an abnormally slow heart rate, poses significant challenges in terms of diagnosis and treatment. While it is a concern world-wide, low- and middle-income countries (LMICs) face substantial barriers in accessing appropriate bradycardia therapy. This article aims to explore the global aetiology and incidence of bradycardia, compare the prevalence and management of the condition in high-income countries versus LMICs, identify the key reasons behind the disparities in access to bradycardia therapy in LMICs, and emphasize the urgent need to address these disparities to ensure equitable healthcare on a global scale.

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.

Clinical valuation of ST changes in a group of patients with ventricular arrhythmias: The inSighT Study.

BACKGROUND: The inSighT study was designed to determine the prevalence of ischemic changes as recorded by implantable cardioverter-defibrillator (ICD) ST deviations in intracardiac electrocardiograms (EGM) over the 24 h preceding malignant ventricular arrhythmias (VT/VF). METHODS: The study enrolled patients with known coronary artery disease (CAD) or high risk of future development of CAD implanted with an ICD equipped with an ST monitoring feature (Ellipse™/Fortify Assura™, St. Jude Medical). Device session records were collected at each in-clinic follow-up. EGM ST levels of the beats over the 15 minutes prior to VT/VF events were compared using a t test with those from a baseline period of 23-24 h prior to the VT/VF event. All events with p < .05 were visually inspected to confirm they were evaluable; additional criteria for exclusion from further analysis included inappropriate therapy, aberrant conduction, and occurrence of VT/VF within 24h prior to the current event. RESULTS: The study enrolled 481 ICD patients (64 ± 11 years, 83% male) in 14 countries and followed them for 15±5 months. A total of 165 confirmed VT/VF episodes were observed, of which 71 events (in 56 patients, 34% of all patients with VT/VF) were preceded by significant (p < .05) ST-segment changes unrelated to known non-ischemic causes. None of the analyzed demographic and clinical factors proved to be associated with greater odds of presenting with ST-segment changes prior to VT/VF episode. CONCLUSION: In this exploratory study, characteristic ST-segment changes, likely representative of ischemic events, were observed in 34% of all patients with VT/VF episodes.

CRT Efficacy in "Mid-Range" QRS Duration Among Asians Contrasted to Non-Asians, and Influence of Height.

OBJECTIVES: The purpose of this study was to test the hypotheses that cardiac resynchronization therapy (CRT) efficacy differed among Asians compared with non-Asian populations, differed between QRS duration (QRSd) ranges 120-149 and ≥150 ms, and was influenced by height in the multinational ADVANCE CRT trial. BACKGROUND: CRT guidelines, derived from trials among U.S./European patients, assign weaker recommendations to those with midrange QRSd (QRSd <150 ms). Patient height may modulate CRT efficacy. Together, these may affect CRT prescription and efficacy in Asia. METHODS: CRT response was assessed using the Clinical Composite Score 6 months postimplant (n = 934). Heart failure events and cardiac deaths were reported until 12 months. Asian and non-Asian patients were compared overall, by QRSd <150 ms (Asian n = 71 vs non-Asian n = 248), and QRSd ≥150 ms (Asian n = 180 vs non-Asian n = 435) and by height. RESULTS: Asians comprised 27% (251 of 934) of the primary study population. More Asians had QRSd ≥150 ms (72% [180 of 251] vs 64% [435 of 683] in non-Asian patients; P = 0.022). Overall CRT response was better in Asians vs non-Asians (Clinical Composite Score 85% vs 65%; P <0.001), and following QRSd dichotomization (QRSd <150 ms: 80% vs 59%; P <0.001; QRS ≥150 ms: 86% vs 69%; P < 0.001). HF events and cardiac deaths were fewer in Asians irrespective of QRSd (P < 0.001). Stepwise multivariable analysis indicated that in group QRSd <150 ms, nonischemic cardiomyopathy, number of other comorbidities (0-1 vs ≥4), and atrial fibrillation influenced CRT response. The trend favoring Asian race (OR: 1.46; 95% CI: 0.72-2.95) was eliminated (OR: 1.00; 95% CI: 0.47-2.11) when height or QRSd/height were included (QRSd/height P = 0.006; OR: 1.64; 95% CI: 1.15-2.35). In QRSd <150 ms, probability of CRT response diminished as height increased, but increased with QRSd/height, in both Asians and non-Asians. In QRSd ≥150 ms, height or QRSd/height had minimal effect in Asians or non-Asians. CONCLUSIONS: Height modulates CRT efficacy among patients with QRSd <150 ms and contributes to high probability of benefit from CRT among Asians. CRT should be encouraged among Asian patients with midrange QRSd. (Advance Cardiac Resynchronization Therapy [CRT] Registry; NCT01805154).

Advanced heart failure beckons: where are the cardiologists?

Advanced Heart Failure is one of the leading causes of death and hospitalization worldwide. Its incidence is increasing steadily in India as well. Despite a huge need, not many cardiologists take heart failure as a career option. The present article seeks to explore the potential reasons for this lack of interest among cardiologists of the country. It also briefly attempts to suggest remedial actions.

Profiling cardiac arrhythmia and heart failure patients in India: The Pan-arrhythmia and Heart Failure Observational Study.

BACKGROUND: The PANARrhythMia and Heart Failure Registry (PANARM HF) characterized demographic, clinical and interventional therapy indication profiles of cardiac arrhythmia (CA) and heart failure (HF) patients in India. METHODS: Consulting Physicians (CP) who medically manage CA and HF patients enrolled patients with one or more of the following: syncope, pre-syncope, dyspnea, palpitation, fatigue and LV dysfunction. The CPs were trained by interventional cardiologists (IC) to identify CA/HF patients indicated for implantable device/radiofrequency ablation (RFA). 59 CP's, 16 IC's & 2205 patients from 12 cities participated. Demographic, clinical, device/RFA indication and referral-consultation profiles were created. IC's provided device/RFA recommendations based on these profiles. RESULTS: The CA/HF distribution of patients was: HF - 58%, bradyarrhythmia - 15%, atrial fibrillation - 15%, other supraventricular tachyarrhythmia - 10% and ventricular tachycardia/fibrillation - 4.5%. 62% of the CA/HF population was male and 45% were below age 60. Coronary artery disease (52%), hypertension (44%), diabetes (30%) & myocardial infarction (20%) were prominent. 1011 (46%) of the CA/HF population were potential device/RFA candidates according to the IC's. However, only 700 (69%) of these patients were referred to the IC by the CP. Of referred patients, only 177 (25%) consulted the IC and were recommended therapy. Thus, 824 (83%) of patients indicated for interventional therapy were not advised therapy or did not opt for it. CONCLUSION: The India PANARM HF study provides new information and insights into the demographic, clinical, interventional therapy, referral and consultation pattern profiles of CA/HF patients in India.