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.

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.

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.

Echocardiography for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary life support for patients in cardiac and/or respiratory failure. Echocardiography provides essential diagnostic and anatomic information prior to ECMO initiation, allows for safe and efficient ECMO cannula positioning, guides optimization of flow, provides a modality for rapid troubleshooting and patient evaluation, and facilitates decision-making for eventual weaning of ECMO support. Currently, guidelines for echocardiographic assessment in this clinical context are lacking. In this review, we provide an overview of echocardiographic considerations for advanced imagers involved in the care of these complex patients. We focus predominately on new cannulas and complex cannulation techniques, including a special focus on double lumen cannulas and a section discussing indirect left ventricular venting. Echocardiography is tremendously valuable in providing optimal care in these challenging clinical situations. It is imperative for imaging physicians to understand the pertinent anatomic considerations, the often complicated physiological and hemodynamic context, and the limitations of the imaging modality.

Three-dimensional echocardiographic assessment of the aortic valve and the aorta.

We describe the role of three-dimensional echocardiography in the assessment of the aortic valve and the aorta. The manuscript is heavily illustrated with figures and movie clips.

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.

Pre-heart failure at 2D- and 3D-speckle tracking echocardiography: A comprehensive review.

Chronic heart failure (CHF) has different stages and includes pre-HF (PHF), a state of high risk of developing myocardial dysfunction and advanced CHF. Some major behavioral risk factors of PHF might predispose to biological risk factors such as obesity, diabetes mellitus, dyslipidemia, hypertension, myocardial infarction, and cardiomyopathy. These risk factors damage the myocytes leading to fibrosis, apoptosis, cardiac hypertrophy, along with alterations in cardiomyocyte' size and shape. A condition of physiological subcellular remodeling resulting into a pathological state might be developed, conducting to PHF. Both PHF and heart failure (HF) are associated with the activation of phospholipases and protease, mitochondrial dysfunction, oxidative stress and development of intra-cellular free Ca2+  [Ca2+ ]i overloading to an elevation in diastolic [Ca2+ ]i . Simultaneously, cardiac gene expression is activated leading to further molecular, structural and biochemical changes of the myocardium. The sub-cellular remodeling may be intimately involved in the transition of cardiac hypertrophy to heart failure. 2D- and 3D-speckle tracking echocardiography (STE) have been used to quantify regional alterations of longitudinal strain and area strain, through their polar projection, which permits a further assessment of both sites and degrees of myocardial damage. The examination of strain can identify sub-clinical cardiac dysfunction or cardiomyocyte remodeling. During remodeling of the myocardium cardiac strain is attenuated, therefore it is an indicator of disease assessment.

Incremental value of three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of a partially detached MitraClip.

We describe an elderly male patient with two MitraClip devices, one fixed and the other detached, in whom live/real-time three-dimensional echocardiography (3DTEE) provided incremental value and additional information compared to two-dimensional transesophageal echocardiography (2DTEE). 3DTEE offered the ability to comprehensively assess the mitral valve (MV) utilizing full volume and multiplanar reconstruction (MPR) modes. 3DTEE proved useful in assessing the position of the properly attached and the partially detached MitraClip, including assessment of orifice size and degree of mitral regurgitation (MR). In addition, trapping of MV chordae by both clips was noted in the 3DTEE image dataset and confirmed at the time of surgery. Chordal trapping was not detected by 2DTEE. 3DTEE proved useful in more accurately estimating the severity of residual MR with the MitraClips in place since the regurgitant jet vena contracta (VC) could be viewed en face and VC area measured by planimetry in the correct imaging plane as compared to limited linear images from 2DTEE.

Utility of transesophageal echocardiography to assess real time left atrial pressure changes and dynamic mitral regurgitation following placement of transseptal multistage venous cannula for systemic venous drainage and indirect left ventricular venting in venoarterial extracorporeal membrane oxygenation.

A patient with heart failure due to nonischemic cardiomyopathy presented as a transfer to our institution following peripheral (femoral) venoarterial (VA) extracorporeal membrane oxygenation (ECMO) placement. With peripheral VA ECMO cannulation, the patient continued to have unstable ventricular tachyarrhythmias. Echocardiography demonstrated left ventricular (LV) dilation and severe mitral regurgitation (MR) with clinical and chest X-ray evidence of pulmonary edema. To provide venous drainage and simultaneous decompression of the left atrium (LA) and thereby indirect LV venting, a single multistage venous cannula was placed across the inter-atrial septum (IAS) using the previously described left atrial venoarterial (LA-VA) ECMO cannulation technique. Two- and three-dimensional (3D) transesophageal echocardiography (TEE) demonstrated utility in guiding cannula placement into the appropriate position and providing real time assessment of ventricular decompression and MR severity. There was subsequent improvement in pulmonary edema. This case is thought to be the first demonstration of real time resolution of pulmonary venous flow reversal in a patient undergoing LA-VA ECMO cannulation. This demonstration offers important mechanistic insight into some of the potential benefits of such an approach.

Prevalence and follow-up of subclinical rheumatic heart disease among asymptomatic school children in a north-western district of India based on the World Heart Federation echocardiographic criteria.

BACKGROUND: The present study is based on the World Heart Federation (WHF) echocardiographic criteria to assess the prevalence of subclinical rheumatic heart disease (RHD) and elucidate evolution of the disease when the cases were placed on appropriate antibiotic prophylaxis and regular follow-up. The prevalence of subclinical RHD reported by previous active surveillance studies among asymptomatic school children is not comparable to our study because of major differences in screening methods. METHODS: A random inclusion strategy was adopted to recruit urban and rural school children of Bikaner district in the state of Rajasthan, India. The diagnosis of RHD was based on the echocardiographic criteria proposed by the WHF. All studies were reported on-site by a single experienced cardiologist and the digitally preserved studies were reported by a second cardiologist off-site. The final diagnosis was made by consensus. The second echocardiogram was performed for cases diagnosed with RHD after two years from start of study to document early evolution of the disease with ongoing antibiotic prophylaxis. RESULTS: A high prevalence of subclinical RHD was observed in the study population. Pathological mitral and/or aortic valve regurgitation was the commonest lesion, and a significant proportion of cases improved while on regular antibiotic prophylaxis. No case showed fixity of leaflets/ stenosis. CONCLUSION: The prevalence of subclinical RHD is high in the study population, and the disease seems to regress over time in the presence of appropriate antibiotic prophylaxis.

Echocardiography, lung ultrasound, and cardiac magnetic resonance findings in COVID-19: A systematic review.

BACKGROUND: The manifestations of COVID-19 as outlined by imaging modalities such as echocardiography, lung ultrasound (LUS), and cardiac magnetic resonance (CMR) imaging are not fully described. METHODS: We conducted a systematic review of the current literature and included studies that described cardiovascular manifestations of COVID-19 using echocardiography, CMR, and pulmonary manifestations using LUS. We queried PubMed, EMBASE, and Web of Science for relevant articles. Original studies and case series were included. RESULTS: This review describes the most common abnormalities encountered on echocardiography, LUS, and CMR in patients infected with COVID-19.

Incremental value of live/real-time three-dimensional transthoracic echocardiography over the two-dimensional technique in the assessment of left ventricular endocardial rupture with myocardial dissection and contained apical epicardial rupture following myocardial infarction.

We report the incremental value of live/real-time three-dimensional transthoracic echocardiography (3DTTE) over two-dimensional transthoracic echocardiography (2DTTE) in making a definitive diagnosis of left ventricular endocardial rupture with myocardial dissection and contained apical epicardial rupture in an elderly male patient presenting with acute myocardial infarction. To the best of our knowledge, this has not been described previously.

Echocardiography 2020: Toward deciphering the "Rosetta stone" of left ventricular diastolic function.

In the year 1997, nearly a quarter-century ago, Nishimura and Tajik (J Am Coll Cardiol. 1997;30:8) suggested that Doppler echocardiography was the "Rosetta stone" (a metaphor for decrypting secrets of diastole) of left ventricular diastole, based solely on transmitral E/A ratio and its progression from grade I through IV, supported by cardiac catheterization, as the filling pressure started to increase to over 15 mm Hg. Ten years later, in 2007, the same Mayo group (Nagueh et al, J Am Coll Cardiology. 2008;51:679) was searching to decipher the secrets of diastole using multiple measures such as left atrial (LA) volume, E/E' ratio, pulmonary venous flow, and mitral inflow propagation velocity. This substantial leap from E/A ratio led to the more formal recommendation proposed by the American Society of Echocardiography in 2009 (Nagueh et al, J Am Soc Echocardiogr. 2009;22:107) and, as an update, in the year 2016 (Nagueh et al, J Am Soc Echocardiogr. 2016;29:277): the later version gained popularity for the simplified approach to identify diastolic dysfunction in healthy subjects as well as in those with poorly contracting left ventricle. Despite 30 years of continuous search, we are not sure if we have been able to decipher the hidden secrets of diastolic function. With this background, the Echocardiography Journal under the leadership of Dr Navin Nanda as the Editor-in-Chief has taken this initiative to publish a theme issue on left ventricular diastolic function and when this becomes dysfunctional to diminish life.

Utility of three-dimensional transesophageal echocardiography to guide transseptal positioning of a single multistage venous cannula to provide both venous drainage and indirect left ventricular venting in veno-arterial extracorporeal membrane oxygenation.

A patient with heart failure due to dilated ischemic cardiomyopathy presented in cardiogenic shock for institution of veno-arterial extracorporeal membrane oxygenation as a bridge to cardiac transplantation. To provide adequate venous drainage and simultaneous decompression of the left atrium (indirect left ventricular venting), a single venous cannula was placed across the interatrial septum so that the distal orifice and side ports were located within the left atrium and the proximal set of side ports were positioned at the cavoatrial junction. Three-dimensional transesophageal echocardiography demonstrated utility in guiding cannula placement and appropriate positioning within the left atrium.

Two-dimensional transthoracic echocardiographic finding of left atrial compression resulting from blunt trauma to the thoracic spine.

We present an adult female in whom two-dimensional transthoracic echocardiography demonstrated encroachment of the thoracic spine on the left atrium (LA) resulting in a very small, compressed LA cavity by a prominent thoracic spine shadow. Computed tomography (CT) scan of the chest showed compression of the LA produced by localized anterior deformation of the thoracic spine which had resulted from blunt injury to her spine following a fall from a swing several years previously.