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.

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.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Atrial Speckle Tracking Echocardiography for Detecting Atrial Fibrillation in Cryptogenic Stroke: A Meta-Analysis.

Cryptogenic stroke (CS) accounts for approximately 25% of ischemic stroke cases, with atrial fibrillation (AF) accounting for 30% of CS cases. We investigated the utility of left atrial (LA) speckle-tracking echocardiography in identifying patients at high risk of AF after CS and potentially guiding patients who will benefit from long-term rhythm monitoring devices. Cochrane Library, MEDLINE, and EMBASE were searched for relevant studies. We included studies that examined patients with new CS without a history of AF and further examined LA strain parameters (peak and/or reservoir strain). Continuous data were pooled as a mean difference (MD) comparing patients who developed AF vs no AF.  We used the inverse variance method with the DerSimonian-Laird estimator for tau2 and Hartung-Knapp adjustment for random effect analysis. I2 was used to assess heterogeneity. Thirteen observational studies met our criteria and included 3031 patients with new CS. Of those, 420 patients developed AF on follow-up, and 2611 patients did not develop AF. The AF group vs. no AF had significantly reduced LA reservoir strain (LARS) [MD: -8.61; 95% CI: -10.76, -6.47, I2 = 85%, p < 0.01] at presentation. LARS is significantly lower in patients who developed AF after CS. More studies are needed to validate this data.

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.

Three-dimensional echocardiography of the tricuspid valve.

Due to the proportionally high mortality rates associated with isolated tricuspid valve surgery, the invasive treatment of such pathology, historically, has been left largely unaddressed. Recently, there has been an appreciation for the mortality and morbidity of tricuspid valve disease, giving rise to the movement towards identifying less invasive, transcatheter approaches for treatment. Due to the technical complexity of these procedures along with the uniqueness and variability of tricuspid valve anatomy, a better appreciation of the tricuspid valve anatomy and pathology is required for pre-procedural planning. While two-dimensional echocardiography serves as the initial non-invasive modality for tricuspid valve evaluation, three-dimensional echocardiography provides a complete en face view of the tricuspid valve and surrounding structures, as well contributes further information regarding disease etiology and severity. In this review, we discuss the utility of three-dimensional echocardiography as a supplement to two-dimensional imaging to better assess tricuspid valve disease and anatomy to aide in future innovative therapies.

Imaging modality for left ventricular ejection fraction estimation and effect of implantable cardioverter-defibrillator on mortality in patients with heart failure.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs count-based, respectively). OBJECTIVE: The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF ≤35% varied on the basis of LVEF measured by 2DE or MUGA. METHODS: Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n = 971) or MUGA (n = 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. RESULTS: Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.46-1.11), respectively (P = .693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. CONCLUSION: We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF.

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.

Utilization of Two- and Three-Dimensional Transesophageal Echocardiography in Successfully Guiding Transcatheter Mitral Valve in Bioprosthetic Mitral Valve/Mitral Ring Implantation without Complications in Patients with Thrombus in Left Atrium/Left Atrial Appendage.

BACKGROUND: The aim of this study is to describe, for the first time to our knowledge, the utilization of both two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE) in successfully performing transcatheter mitral valve (MV) in bioprosthetic MV/MV annulopasty ring implantation using the apical approach in 12 patients (pts) with co-existing left atrial appendage (LAA) and/or LA (left atrium) body thrombus, which is considered a contraindication for this procedure. METHODS AND RESULTS: All pts were severely symptomatic with severe bioprosthetic MV stenosis/regurgitation except one with a previous MV annuloplasty ring and severe native MV stenosis. Thrombus in LAA and/or LA body was noted in all by 2D and 3DTEE. All were at high/prohibitive risk for redo operation and all refused surgery. Utilizing both 2D and 3DTEE, especially 3DTEE, guidewires and the prosthesis deployment system could be manipulated under direct vision into the LA avoiding any contact with the thrombus. The procedure was successful in all with amelioration of symptoms and no embolic or other complications over a mean follow-up of 21 months. CONCLUSION: Our study demonstrates the feasibility of successfully performing this procedure in pts with thrombus in LAA and/or LA body without any complications.

Coronary flow abnormalities in chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Coronary vasomotion abnormalities have been described in small studies but not studied systematically. We aimed to review the present literature and analyze it to improve our understanding of chronic kidney disease (CKD) related-coronary microvascular dysfunction. OBJECTIVE: Coronary flow reserve (CFR) is a well-known measure of coronary vasomotion. We aimed to assess the difference in CFR among participants with and without CKD. METHODS: PubMed, Embase, and Cochrane CENTRAL were systematically reviewed to identify studies that compared CFR in participants with and without CKD. We estimated standardized mean differences in mean CFR reported in these studies. We performed subgroup analyses according to imaging modality, and the presence of significant epicardial coronary artery disease. RESULTS: In 14 observational studies with 5966 and 1410 patients with and without CKD, the mean estimated glomerular filtration rate (eGFR) was 29 ± 04 and 87 ± 25 ml/min/1.73 m2 , respectively. Mean CFR was consistently lower in patients with CKD in all studies and the cumulative mean difference was statistically significant (2.1 ± .3 vs. 2.7 ± .5, standardized mean difference -.8, 95% CI -1.1, -.6, p < .05). The lower mean CFR was driven by both significantly higher mean resting flow velocity (.58 cm/s, 95% CI .17, .98) and lower mean stress flow velocity (-.94 cm/s, 95% CI -1.75, -.13) in studies with CKD. This difference remained significant across diagnostic modalities and even in absence of epicardial coronary artery disease. In meta-regression, there was a significant positive relationship between mean eGFR and mean CFR (p < .05). CONCLUSION: Patients with CKD have a significantly lower CFR versus those without CKD, even in absence of epicardial coronary artery disease. There is a linear association between eGFR and CFR. Future studies are required to understand the mechanisms and therapeutic implications of these findings. KEY POINTS: In this meta-analysis of observational studies, there was a significant reduction in coronary flow reserve in studies with chronic kidney disease versus those without. This difference was seen even in absence of epicardial coronary artery disease. In meta-regression, a lower estimate glomerular filtration rate was a significant predictor of lower coronary flow reserve. Coronary microvascular dysfunction, rather than atherosclerosis-related epicardial disease may underly increase cardiovascular risk in a patient with chronic kidney disease.

Artificial intelligence in echocardiography: Review and limitations including epistemological concerns.

BACKGROUND AND PURPOSE: In this review we describe the use of artificial intelligence in the field of echocardiography. Various aspects and terminologies used in artificial intelligence are explained in an easy-to-understand manner and supplemented with illustrations related to echocardiography. Limitations of artificial intelligence, including epistemologic concerns from a philosophical standpoint, are also discussed. METHODS: A narrative review of relevant papers was conducted. CONCLUSION: We provide an overview of the usefulness of artificial intelligence in echocardiography and focus on how it can supplement current day-to-day clinical practice in the assessment of various cardiovascular disease entities. On the other hand, there are significant limitations, including epistemological concerns, which need to be kept in perspective.

Meta-analysis Comparing Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting for Non-ST Elevation Acute Coronary Syndrome in Patients With Multivessel or Left Main Disease.

Outcomes of patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) with multivessel coronary disease (MVD) and/or unprotected left main coronary artery disease (CAD) revascularized with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is not well defined. MEDLINE/PubMed and EMBASE/Ovid were queried for studies that investigated PCI vs CABG in this disease subset. The primary outcome was major cardiac adverse events (MACE) at 30 days and long-term follow-up (3-5 years). The final analysis included 9 studies with a total of 9299 patients. No significant difference was observed between PCI and CABG in 30 days MACE (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.38-2.39, all-cause mortality, myocardial infarction, and stroke. A meta-regression analysis revealed patients with a history of PCI had higher risk of MACE with PCI as compared with CABG. At long-term follow-up, PCI compared with CABG was associated with higher risk of MACE (RR 1.52; 95% CI 1.28-1.81), myocardial infarction, and repeat revascularization, while no difference was observed in the risk of stroke and all-cause mortality. In patients with NSTE-ACS and MVD or unprotected left main CAD, no differences were observed in the clinical outcomes between PCI and CABG at 30 days follow-up. With long-term follow-up, PCI was associated with a higher risk of MACE.

Right Heart Chambers Longitudinal Strain Provides Enhanced Diagnosis and Categorization in Patients With Pulmonary Hypertension.

Background: Increased systolic pulmonary arterial pressure (sPAP) could lead to the mechanical dysfunction and myocardial fibrosis of the right heart chambers. Echocardiographic strain analysis has not been adequately studied in patients with pulmonary hypertension (PH). Study design and methods: A cross-sectional cohort of patients with suspected PH and echocardiographic strain evaluation was recruited. The cut-off values of peak tricuspid regurgitation velocity (TRV) with the low probability of PH (≤2.8 m/s), intermediate probability (2.9-3.4 m/s, without other echo PH signs), and high probability of PH (2.9-3.4 m/s with other echo PH signs and >3.4 m/s) categories were studied by right ventricular and right atrial (RA) strain analysis in a sample of 236 patients. Results: The results showed that 58 (56.9%) patients had low, 15 (14.7%) had intermediate, and 29 (28.4%) had a high probability of PH. We observed a negative association between right ventricular free wall strain (RV-FWS) and atrial global strain with sPAP. With the increase in PH severity, RA reservoir, conduit, and contraction (booster) strain values decreased. The identified cut-off values of strain parameters had an adequate ability to detect PH severity categories. In addition, the post-mortem biopsies of right heart chambers from subjects with known severe PH were analyzed to quantify myocardial fibrosis. Our sample of right heart biopsies (n = 12) demonstrated an association between increased sPAP before death and right ventricular and RA fibrosis. Conclusion: Mechanical dysfunction and fibrosis in the right chambers are associated with increased sPAP. Right ventricular and atrial strain could provide enhancement in the diagnosis and categorization of subjects with suspected PH.

Paradoxical Septal Motion after Uncomplicated Cardiac Surgery: A Consequence of Altered Regional Right Ventricular Contractile Patterns.

Paroxysmal interventricular septal motion (PSM) is the movement of the septum toward the right ventricle (RV) during cardiac systole. It occurs frequently after uncomplicated cardiac surgery (CS), including coronary bypass (on-pump and off-pump), valve repair or replacement, and with all types of incisions (sternotomy or mini-thoracotomy). It sometimes resolves quickly but may persist for months or become permanent. Global RV systolic function, stroke volume and ejection fraction remain normal after uncomplicated CS, but regional contractile patterns are altered. There is a decrease in longitudinal shortening but an increase in transverse shortening in the endocardial and epicardial right ventricular muscle fibers, respectively. PSM is a secondary event as there is no loss of septal perfusion or thickening. The increased RV transverse shortening (free wall to septal fibers) may modify septal movement resulting in PSM that compensates for the reduced RV longitudinal shortening, thus preserving normal global right ventricular function.