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Objective: To quantitate left ventricular mass index (LVMI) and correlate it with inflammation, insulin resistance (IR) and serum androgen levels among nonobese normotensive women with polycystic ovary syndrome (PCOS)., Design: Cross-sectional study SETTING: Tertiary care institute in North India PATIENTS: A total of 260 drug-naive women qualifying the Rotterdam 2003 criteria for diagnosis of PCOS and 250 apparently healthy women matched for age and body mass index (BMI)., Interventions: Clinical, biochemical, hormonal, and inflammatory marker assessment was followed by estimation of LVM and LVMI by 2-dimensional echocardiography., Main Outcome Measures: LVM and LVMI in nonobese, normotensive women with PCOS and its correlation with subinflammation, IR, and androgen excess., Results: Mean ages (28.08 ± 4.18 vs. 29.44 ± 6.33 years) and BMI (24.43 ± 4.15 vs. 23.92 ± 4.21 kg/m 2 ) of cases vs. controls were comparable, as was blood pressure and plasma glucose (1 hour after oral glucose tolerance test [OGTT]). Women with PCOS had fewer menstrual cycles per year and higher Ferriman-Gallwey scores, plasma insulin, homeostasis model assessment of IR, total testosterone, plasma glucose (fasting and 2 hours after OGTT), serum high-sensitive C-reactive protein, tumor necrosis factor-α, and interleukin-6 than did the controls (P<.001). Significant differences were observed in LVM (101.50 ± 30.19 vs. 89.35 ± 27.57 g) and LVMI (63.60 ± 16.67 vs. 56.32 ± 10.84 g/m 2 ) between women with PCOS and the controls (P<.001). Multivariate analysis revealed that proinflammatory markers and IR rather than hyperandrogenism correlated with LVMI., Conclusion: We conclude that normotensive nonobese women with PCOS were more likely to have elevated mean LVMI than were healthy controls and it was positively correlated with proinflammatory markers and IR but not with androgen excess. Well-designed long-term follow-up studies with a larger cohort of subjects with comprehensive cardiovascular risk assessment are warranted to conclusively answer the question., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Intracoronary thrombus is common in patients with ST-elevation myocardial infarction (STEMI). Percutaneous coronary intervention (PCI) is the treatment of choice for these patients. Intracoronary thrombus is still a challenge during PCI in STEMI, even with dual antiplatelets, glycoprotein IIb/IIIa inhibitor, and anticoagulation. Intracoronary thrombus can cause distal or nonculprit vessel embolization and no-reflow state. No reflow results in large infarct size, adverse left ventricular remodeling, arrhythmias, and death. Recently, catheter-directed intracoronary thrombolysis (ICT) is gaining acceptance in patients with no-reflow due to a large thrombus burden. Aim: Evaluation of catheter-directed ICT in patients with acute STEMI who develop no reflow due to large thrombus burden during PCI. Materials and Methods and Results: This was a retrospective observational study conducted after approval of the institutional ethics committee in a tertiary care hospital of north India from April 15, 2021 to April 14, 2022, included 1020 adult patients who had undergone coronary evaluation. 37.25% patients had PCI, among these 10% had PCI for acute STEMI. Thrombolysis in myocardial infarction (TIMI) Grade 5 in 79.17% and Grade 4 in 20.83%. ICT was done with low-dose tenecteplase (15 ± 5 mg). The TIMI flow III in 91.67% and II in 8.33% of patients was achieved after intracoronary thrombolysis. Major risk factor was tobacco smoking in 41.67%, and the major complication was left ventricular failure in 33.33%. Conclusions: Catheter-directed ICT is safe and effective in reducing thrombus burden, thus improving myocardial reperfusion in STEMI. This condition has a grave prognosis and can lead to adverse cardiac outcomes. There are many drugs that have been tried to manage no reflow. The use of ICT to treat no-reflow state can be life saving with minimal systemic side effects. [ABSTRACT FROM AUTHOR]

Angiotensin receptor/neprilysin inhibitors (ARNI) have become a pillar of heart failure (HF) management. Clinicians gain practical insight into the use of sacubitril/valsartan in patients with HF with reduced ejection fraction (EF) from a comprehensive overview based on clinical experience with ARNI therapy. The objective was to develop a consensus document addressing common concerns regarding the use of ARNI in patients with HF in clinical settings in India. Subject matter experts (SMEs) from India with decision-making expertise in the management of HF were identified to address experiences of ARNI use in Indian patients, its function in reversing myocardial remodeling, improvement in health status, and its safety. In regional meetings, five SMEs from India who consented to participate discussed data from practical experiences and current evidence. ARNI has been shown to substantially enhance EF 5%–10% in a majority of HF patients, although the range of improvement could vary widely in a few patients. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blocker antagonists have been eclipsed by ARNI. Patients who have diminished or declining estimated glomerular filtration rates are more likely than those with normal renal function to experience hyperkalemia. It is prudent to consistently monitor potassium levels in patients with borderline chronic kidney disease. In India, potassium binders may be used to temporarily control hyperkalemia caused by ARNI. Patients with a systolic blood pressure of <100 mmHg may initiate taking ARNI while being tracked for clinical symptoms. In clinical practice, symptomatic improvement with ARNI is observed soon after initiating, even before alterations noted in echocardiography. [ABSTRACT FROM AUTHOR]

Objective- The aim of this study was to assess whether major blood inflammatory parameters like neutrophil/lymphocyte ratio (NLR), interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) levels are associated with left ventricular remodeling parameters, New York heart association (NYHA) functional classes and pro-B- type natriuretic peptide (pro-BNP) levels in patients with idiopathic DCM. Methodology-59 patients with DCM were initially screened and categorized as idiopathic DCM and 22 were included for further analyses due to COVID-19 restrictions and positive cases were eliminated from the study. Biochemical assessment and echocardiographic investigations were done to assess cardiac structure and function. Results- There was a statistically significant correlation found between NLR and NYHA functional class (r=0.48, p<0.001), pro-BNP level (r=0.61, P<0.001) and left ventricular (LV) systolic parameters. Similar correlation was observed for IL-6 (with NYHA, r=0.40, P=0.011 and with pro-BNP, r=0.55, P=0.002). hs-CRP showed low to moderate correlation with the cardiac markers. NLR was also significantly higher in NYHA functional class III-IV patients (n=11) compared to NYHA class I-II (n=11), (3.1±0.5 vs 3.8±0.8, P=0.045). IL-6 showed similar significant difference between NYHA class I-II and III-IV (10.0±2.6 vs 20.0±11.2, P=0.045). NLR and IL-6 also found to be independent positive predictors of heart failure progression in NYHA class III-IV (P=0.019 and 0.015 respectively). Conclusion- Our findings clearly exhibit the efficacy of NLR and IL-6 in predicting severity of chronic heart failure in IDCM patients. [ABSTRACT FROM AUTHOR]

Individuals of Indian Asian ethnicity living in the U.K. have at least a 50% excess of cardiovascular disease (CVD) mortality compared with European whites, yet there are no validated tools capable of identifying this excess risk. Left ventricular hypertrophy (LVH) is a powerful prognosticator for future CVD events but its prevalence in Indian Asians is unknown. We examined the prevalence of LVH and the degree of concentric remodeling amongst healthy U.K. Indian Asians compared with European whites recruited to the LOLIPOP (London Life Sciences Prospective Population) study. Transthoracic echocardiography was performed in 2127 subjects aged 35-75 years without history of clinical CVD events. The prevalence of LVH was defined and relative wall thickness was calculated to provide a measure of concentric remodeling. The prevalence of LVH was significantly higher amongst Indian Asian men as compared with European white men, with an unadjusted odds ratio (OR) of 1.8 (95% CI: 1.4-2.6). Following adjustment for clinical and hemodynamic variables, the magnitude of this effect increased (OR 2.8, 95% CI: 1.9-4.2). The degree of concentric remodeling was higher amongst Indian Asians as compared with European whites (adjusted relative wall thickness for men: 0.41 vs. 0.39, P<0.001; women: 0.40 vs. 0.38, P<0.01). An almost threefold higher prevalence of LVH amongst Indian Asian men and a greater degree of concentric remodeling amongst Indian Asian men and women was evident. Investigation of the mechanisms underlying the pathogenesis of LV remodeling and blood pressure etiology may help redress the excess CVD mortality observed in Indian Asians.

Heart failure (HF) is responsible for substantial morbidity and mortality and is increasing in prevalence. Although there has been remarkable progress in the treatment of HF with reduced ejection fraction (HFrEF), morbidity and mortality are still substantial. Cardiac contractility modulation (CCM) signals, consisting of biphasic high-voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period, have been shown to improve symptoms, exercise tolerance and quality of life and reduce the rate of HF hospitalizations in patients with ejection fractions (EF) between 25% and 45%. CCM therapy is currently approved in the European Union, China, India, Australia and Brazil for use in symptomatic HFrEF patients with normal or slightly prolonged QRS duration. CCM is particularly beneficial in patients with baseline EF between 35% and 45%, which includes half the range of HF patients with mid-range EFs (HFmrEF). At the cellular level, CCM has been shown in HFrEF patients to improve calcium handling, to reverse the foetal myocyte gene programme associated with HF, and to facilitate reverse remodelling. This review highlights the preclinical and clinical literature related to CCM in HFrEF and HFmrEF and outlines the potential of CCM for HF with preserved EF, concluding that CCM may fill an important unmet need in the therapeutic approach to HF across the range of EFs. [ABSTRACT FROM AUTHOR]

Left ventricular hypertrophy (LVH) is an independent predictor of mortality and its prevention can decrease cardiovascular mortality among predialysis chronic kidney disease (CKD) patients. This cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from March 2013 to October 2013 to determine the frequency of LVH and its risk factors in patients with CKD. A total of 135 outpatients with CKD duration longer than three months, were included in this study. All patients underwent laboratory investigations which included serum creatinine, blood counts, serum calcium, phosphate and uric acid, and parathormone. M-mode, two-dimensional echocardiogram in the left decubitus position was performed to document LVH. LVH was labeled when the left ventricular mass index was >131 g/m2 in men and >100 g/m2 in women on echocardiogram. LVH was found in 76 study patients (56.3%). The frequency of LVH was significantly high in patients with stage-4 CKD and those with duration of CKD above 12 months. Other risk factors included low hemoglobin, high serum calcium and phosphate levels, and decreasing estimated glomerular filtration rate. In conclusion, early detection of LVH and control of risk factors may help to achieve a decrease in cardiovascular morbidity and mortality in patients with CKD.

Over the years the age limit for the arterial switch operation (ASO) is being redefined with increasing expertise and adoption of extra-corporeal membrane oxygenator (ECMO) in the surgical program. We conducted a study to see the differences in ultrastructural features in eight children with transposition of the great arteries, four with prepared and the remaining four with regressed left ventricle (LV) during the ASO. Children with prepared LV had prominent Z bands with uniform and round mitochondria, few fat vacuoles and minimal collagen in the background, whereas children with regressed LV had Z band disruption with non-uniform elliptical mitochondria and myofibrillary disarray and an abundance of fat vacuoles and collagen in the background. Children with regressed LV and abundance of collagen had a prolonged postoperative course. Collagen deposition in the LV may point to the situation where the postoperative course following ASO may be prolonged due to the increased time required for the regressed LV to increase its mass and to sustain the systemic circulation.

Background: Systolic heart failure treatment now includes cardiac resynchronization therapy (CRT) as a necessary element. CRT has been shown to have advantageous impacts on mortality, hospitalization rates, and quality of life. Approximately 30% of patients fail to respond to traditional CRT implantation. Aims and Objectives: This study aimed to compare the outcome of dual resynchronization by placing the right ventricular pacing lead at His bundle or left bundle branch area against conventional CRT. Materials and Methods: This longitudinal follow-up study of a total of 35 patients undergoing CRT device placement for assessment of safety, efficacy, and feasibility of the procedure and post-procedural complications and correlation with parameters obtained from electrocardiogram and echocardiography parameters in a tertiary care set up in India. Results: Among this matched population (mean age 64 years) there was a higher responder rate with the newer technique of dual resynchronization compared to conventional CRT (83% vs. 70%). Conclusion: Dual resynchronization therapy is feasible and safe and provides better electrical resynchronization compared to conventional CRT and could be a better alternative, especially when suboptimal electrical resynchronization is obtained. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is an important independent risk factor for the development of cardiovascular and renal disease which has been the cause of death in majority of the diabetic population. Albuminuria has been shown to predict cardiovascular morbidity and mortality in diabetics. Objective: The purpose of this study was to correlate microalbuminuria and left ventricular diastolic dysfunction (earliest manifestation of heart disease) in type 2 diabetes mellitus to aid in subclinical diagnosis, risk stratification, and prompt management of cardiovascular disease in diabetic patients. Methods: This study assessed the incidence of left ventricular diastolic dysfunction (LVDD) using echocardiography and its correlation with microalbuminuria and with other parameters like age, gender, BMI, duration of diabetes mellitus, and glycosylated hemoglobin in 90 normotensive, type 2 diabetic patients in a tertiary care hospital in Western India. Results: The prevalence of LVDD in our study is 59% (n = 53). The mean age of the study subjects was 60.7 years. Out of 59 subjects with BMI ≥ 25 kg/m2, diastolic dysfunction was seen in 31 patients. The mean duration of diabetes mellitus in our study is 11.5 years. Good glycemic control, i.e., HbA1c ≤ 7.0, was seen in 13 patients with LVDD. Out of 53 subjects with LVDD, 48 (90.5%) subjects had microalbuminuria. Conclusion: There is a significant correlation between microalbuminuria and LVDD in type 2 diabetes mellitus, independent of other parameters studied (age, sex, BMI, glycemic control, and duration of diabetes). [ABSTRACT FROM AUTHOR]

Introduction: Left bundle branch pacing (LBBP) involves the deployment of the lead deep inside the septum. Penetration of the septum by the lead depends on the texture of the septum, rapidity of rotations, operator experience, and implantation tools. Objectives: The aim of our study was to assess the behavior of the lumenless lead during rapid rotations and the physiological property of the interventricular septum(IVS) during LBBP. Methods: Patients undergoing LBBP between January 2021 and December 2022 were retrospectively included in the study. Results: Among 255 attempted patients, 20 (7.9%) had procedural failure(no LBB capture—four, inability to penetrate septum—seven, and dislodgements after sheath removal—nine). Septal penetration achieved in 248/255 patients (97.2%). Lead movement inside the IVS was assessed by lead traverse time. Based on the behavior of the IVS (n = 255), three different responses were noted. Type‐I response(normal/firm septum) in 93.7% (n = 239) characterized by constant and progressive movement of lead. Neither perforation nor further change in premature‐ventricular‐complex morphology beyond M‐beat were observed despite additional few unintentional rotations indicating the protective mechanism of LV‐endocardium. Type‐II response(soft/cheesy septum) in 3.5% (n = 9) characterized by hyper‐movement of lead without resistance due to altered texture of septum and poor LV subendocardial barrier resulting in perforation. No patients in this group had LV dysfunction or associated coronary artery disease. In type‐III response, seen in 2.8% (n = 7), lead could not be penetrated due to scar in IVS. Conclusion: Three different patterns of responses were observed during LBBP. The most distinct type‐ll response was associated with soft/cheesy septum with hyper‐movement of the lead predisposing for future dislodgments in patients without structural heart disease. [ABSTRACT FROM AUTHOR]

Introduction: Although much research has been done on adult hypertrophic cardiomyopathy, data on pediatric hypertrophic cardiomyopathy is still limited. Methods and results: The study enrolled all patients with cardiomyopathy who presented to us between 1990 to 2020 and were younger than 18 yrs. During the thirty-year study period, we identified 233 cases of pediatric cardiomyopathy. Sixty-three cases (27%) had hypertrophic cardiomyopathy. Out of the 63 HCM cases, 12% presented in the neonatal period and 37% presented in the first year of life. The median age of presentation was 7 yrs (Range 0.1–18 yrs). Sixteen patients had proven syndromic, metabolic, or genetic disease (25%). LV outflow obstruction was present in 30 patients (47%). Noonan syndrome was present in 9 of the 63 patients (14%). Dyspnea on exertion was the most common mode of presentation. Cardiac MRI was done in 28 patients, out of which 17 had late gadolinium enhancement (LGE). Mid myocardial enhancement was the most common pattern. Four patients had LGE of more than 15%. Over a mean follow-up period of 5.6 years (0.1–30 years), twenty-one were lost to follow-up (33%). Among the patients whose outcome was known, eleven died (26%), and thirty-one (73%) were alive. The 5-year survival rate of HCM patients was 82%, and the 10-year survival rate was 78%. Seven died of sudden cardiac death, three from heart failure, and one from ventricular arrhythmias. Sustained ventricular arrhythmias were seen in three patients and atrial arrhythmias in two. First-degree AV block was seen in 10 patients (15%) and bundle branch blocks (BBB) in five (8%). Eight patients required ICD or transplant (12.7%). Two patients underwent ICD for primary prevention, and one underwent PPI for distal AV conduction disease. Among the various clinical, echocardiographic, and radiological risk factors studied, only consanguinity showed a trend towards higher events of death or ventricular arrhythmias (P-value 0.08). Conclusion: More than one-third of our HCM cohort presented in infancy. LV outflow tract obstruction is common (47%). Mid myocardial enhancement was the most common pattern of late gadolinium enhancement. SCD was the most common cause of death. The outcome in our HCM cohort is good and similar to other population cohorts. Only Consanguinity showed a trend towards higher events of death or ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Worsening heart failure (WHF) is a distinct under-diagnosed and under-treated condition, independent of location of care. Heart failure (HF) progression is punctuated by repeated WHF events, each resulting in reduced cardiac function. One-third of the patients with HF with reduced ejection fraction experience a decompensation event. These decompensation events often result in the emergency department visits and HF hospitalization. Despite its inclusion in recent guidelines, there is no precise definition of WHF or its various forms. It is worth noting that WHF signals a need for treatment optimization as per guideline-directed medical therapy and the addition of novel drugs like a stimulator of soluble guanylate cyclase that benefit this high-risk patient population. This practical document is based on the expert opinion of cardiologists, cardiothoracic surgeons, and physicians that discussed the definition, assessment, pharmacological management, and monitoring of WHF patients in a hospitalized setting. In addition, there is also a need for an expert opinion for the management of WHF in an outpatient setting. [ABSTRACT FROM AUTHOR]

Background: The brain-type natriuretic peptides (BNP) and troponins levels can be used for the risk stratification of patients presenting with acute myocardial infarctions. Elevated levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) can be seen in patients with heart failure (HF) and atrial fibrillation. Objectives: The aim is to evaluate the NT-ProBNP levels and high-sensitive troponin-T (Trop T-HS) levels in patients with ischemic and nonischemic HF and to analyze its association with prognosis. Methods: This prospective observational study was conducted in a tertiary Centre over a period of 2 years. We analyzed NT-ProBNP and Trop T-HS levels of patients with HF, who were admitted to our cardiac intensive care unit. Patients with acute coronary syndrome, myocarditis, and renal failure were excluded from the study. The study population consists of 130 patients, of which 90 patients with ischemic dilated cardiomyopathy (ISDCM) and 40 patients with idiopathic dilated cardiomyopathy (IDCM). They belonged to the New York Heart Association functional classes 3 and 4. The diagnosis was made with the help of a coronary angiogram and transthoracic echocardiogram. We analyzed the NT-ProBNP levels and Trop T-HS of both groups of patients. Results: Males were predominant in both groups, i.e., 70 (77.8%) in the ISDCM patients and 26 (65%) in the IDCM patients. The NT-ProBNP levels were significantly higher among patients with ISDCM compared to patients with (IDCM) dilated cardiomyopathy (8648 ± 6207 pg/mL vs. 3100 ± 2906 pg/mL); P = 0.0008. We analyzed the NT-ProBNP levels of the survivors and nonsurvivors in each group separately. We found that there were significant differences in the levels of NT-ProBNP in the survivors and nonsurvivors in the ISDCM group (7061 ± 3663 vs. 18035 ± 4667 pg/mL); P = 0.0004. However, there was no significant difference between the survivors and nonsurvivors of IDCM patients (4701 ± 737 vs. 6821 ± 1212 pg/mL); P = 0.07. Like the previous analysis, higher levels of Trop T-HS levels were found in patients with ISDCM group compared with IDCM group (26.6 ± 8.5 ng/L vs. 16.3 ± 3.4 ng/L); P = 0.0002. There was also a significant raise of Trop T-HS in the nonsurvivors in the ISDCM group compared to the survivors (28.9 ± 16.3 vs. 65.5 ± 17.0 ng/L): P = 0.0003. Conclusion: In this study, we found that HF patients who were admitted with higher levels of NT-ProBNP and Trop T-HS had a poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Heart Failure is a leading cause of mortality worldwide including India. Most cross sectional studies have demonstrated heart failure is associated with deficiency of essential micronutrients including Vitamin D which may play a important role in pathogenesis of ventricular remodelling in heart failure. Aim: Our study performed aimed to determine the effect of supplementation in patients of Heart Failure presenting with Vitamin D deficiency to our institute on severity of Heart Failure. Design and Method: 97 patients of Heart failure coming to our institute were given conventional therapies for Heart Failure along with Vitamin supplementation based on serum Vitamin D levels and followed up for 3 months. Results: Patient of Heart failure having Vitamin D deficiency had significant reduction in cardiac biomarkers (NT-pro BNP levels), improvement in Left ventricular ejection fraction (LVEF) and more favourable reverse remodelling determined by Left ventricular end diastolic and systolic diameter (LVEDD & LVESD) though quality of life determined by WHODAS 2.0 score did not changed following 12 weeks supplementation of High Dose Vitamin D. Conclusion: Recognising and treatment of Vitamin D deficiency may determine long term prognosis in patients of Heart Failure. [ABSTRACT FROM AUTHOR]

Objectives: Bicuspid aortic valve (BAV) is the most common congenital lesion found in adults. It can be seen in combination with a transverse left ventricular (LV) band. This study aimed to find an essential relationship between the presence of transverse ventricular band and BAV. Methods: A total of 13 patients from a tertiary care centre in India with transverse LV band were investigated during a six-month period from January 2019 to July 2019. LV band thickness and gradients at the site of the LV band were evaluated as part of its effect on LV haemodynamics. The morphology of the aortic valve and LV outflow tract gradients was assessed. Results: The mean age of the participants was 41 years. A majority had a BAV (n = 11). Average thickness of the LV band was 6.2 mm and the average mean aortic gradient was 4 mmHg. Sequestration of blood was noted at the level of the transverse band in all the patients with two separate jets at the left ventricular outflow tract. The anterolateral jet was deflected from the transverse band and showed higher velocity compared to the other jet, causing turbulence at the BAV. No correlation was found between the thickness of the transverse band and aortic valve gradient. Conclusion: Presence of a robust transverse LV band can serve as a surrogate marker for BAV. [ABSTRACT FROM AUTHOR]

Background and Objective: Remogliflozin etabonate is an orally available prodrug of remogliflozin, an inhibitor of renal sodium glucose co-transporter-2 (SGLT2) with antihyperglycemic activity. The present study was conducted to characterize the pharmacokinetic and safety profile of remogliflozin etabonate under fasting and fed conditions at single oral doses of 100 and 250 mg in healthy Asian Indian adults.Methods: Sixty-five healthy, adult Asian Indian male subjects were enrolled in an open-label, two-stage, single-period pharmacokinetic study. Remogliflozin was given under fasting and/or fed conditions as a single oral dose of 100 or 250 mg. The plasma concentrations of remogliflozin etabonate, remogliflozin, and the metabolite GSK279782 were quantified by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were determined from the plasma concentration-time profile by non-compartmental analysis. Safety was assessed through monitoring of adverse events. Descriptive statistics were calculated and reported for all parameters.Results: The plasma concentration profiles showed rapid absorption of the prodrug remogliflozin etabonate and rapid conversion to the active moiety, remogliflozin, which is then further metabolized to another active metabolite, GSK279782. The geometric mean maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) were comparable for all three analytes between the fasted and fed state. The fed/fasted ratio for Cmax ranged from 0.77 to 1.44 at the 100 mg dose, and from 0.80 to 1.12 at the 250 mg dose. The fed/fasted ratio for AUC was 1.22 and 1.35 at 100 and 250 mg, respectively. An early time to Cmax (tmax) was observed for all three analytes while being administered in the fasted state. Both the Cmax and AUClast of all the three analytes increased in a dose-proportional manner under the fasted and fed states. The terminal half-life for remogliflozin ranged from 1.53 to 2.07 h. All three analytes had comparable terminal half-lives irrespective of dose levels or dietary conditions.Conclusions: Following single oral administration at 100 and 250 mg, remogliflozin etabonate showed favorable, linear pharmacokinetics. There were no clinically relevant food effects on the pharmacokinetics at both the 100 and 250 mg dose levels. Remogliflozin etabonate was well-tolerated without any safety concerns or hypoglycemic events.Clinical Trial Registration: Clinical Trial Registry-India identifier number CTRI/2017/10/010043. [ABSTRACT FROM AUTHOR]

Background Percutaneous atrial septal defect ( ASD) device closure is a safe and effective means of reducing or eliminating interatrial shunting. The response of the right heart to device closure is incompletely understood. Aim To evaluate the effects of transcatheter closure of secundum ASD on right ventricle size and function, that is, both systolic and diastolic by transthoracic echocardiography ( TTE) over a 6-month period. Methods Seventy-three patients had 73 device implantations. The patients were assessed with echocardiography before and at 1 and 6 months after procedure. Results Mean age was 26 ± 17 years. Mean ASD size indexed to body surface area ( BSA) was 19.1 ± 8.6 mm/m2. The device size ranged from 12 to 42 mm. One month after closure, there were statistically significant decreases in right ventricular ( RV) basal diameter (3.5 ± 0.7 cm vs. 4.2 ± 0.8 cm), RV/ LV end-diastolic diameter ratio (0.9 ± 0.1 vs. 1.2 ± 0.2), left ventricular eccentricity index ( LVEI) (1.0 ± 0.1 vs. 1.2 ± 0.2), right atrial ( RA) major dimension (4.4 ± 0.8 cm vs. 4.8 ± 1.0 cm), RA end-systolic area (13.2 ± 4.6 cm2 vs. 18.5 ± 6.7 cm2), tricuspid annular plane systolic excursion ( TAPSE) (2.2 ± 1.8 cm vs. 2.8 ± 0.5 cm), tricuspid annular systolic velocity ( TASV or S′) (13.1 ± 3.0 cm/sec vs. 16.0 ± 2.8 cm/sec), E/A (1.4 ± 0.3 vs. 1.7 ± 0.5), and E/e′ (5.9 ± 5.0 vs. 7.2 ± 2.0) in comparison with baseline. Six months after closure, there were statistically significant decreases in RV major dimension (5.9 ± 1.1 cm vs. 6.3 ± 1.0 cm), RV/ LV end-diastolic diameter ratio (0.8 ± 0.1 vs. 0.9 ± 0.1), RA major dimension (4.1 ± 0.8 cm vs. 4.4 ± 0.8 cm), and RA end-systolic area (11.4 ± 3.8 cm2 vs. 13.2 ± 4.6 cm2) in comparison with 1 month post-device closure. After 6 months, there was a statistically insignificant increase in both TASV (13.7 ± 2.8 cm/sec vs. 13.1 ± 3.0 cm/sec) and TAPSE (2.5 ± 1.6 cm/sec vs. 2.2 ± 1.8 cm/sec). There was no significant change in tissue Doppler MPI at baseline, 1 month, and 6 months after closure (0.38 ± 0.19 vs. 0.35 ± 0.15 vs. 0.38 ± 0.13). There was significant decrease in E/e′ from baseline to 1 month and 1 month to 6 months after closure (7.2 ± 2.0 vs. 5.9 ± 5.0 vs. 4.7 ± 1.5). Conclusion RV volumes decreased significantly in the first month after ASD device closure and continued up to 6 months. There was no change in global right ventricular systolic function but a high basal RV systolic function decreased after closure. Some patients had impaired diastolic function before closure of defect, which reversed to normal within 6 months after closure. Diastolic dysfunction in older age-group may be a cause for long duration taken by right heart chambers to regress and deserves further investigation. [ABSTRACT FROM AUTHOR]

Background: Pharmacological stimulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been recognized as a molecular switch in alleviating myocardial injury through modulating oxidative, inflammatory and apoptotic signaling pathways. This study was designed to elucidate the effect of chrysin, a novel PPAR-γ agonist and its functional interaction with TGF-β/MAPKs in isoproterenol-challenged myocardial injury in rats. Methods: Male Wistar Albino rats were either subjected to vehicle (1.5 mL/kg, p.o.) or chrysin (15-60 mg/kg, p.o.) for 28 days. Isoproterenol (85 mg/kg, s.c.) was administered to rats on 27th and 28th day to induce myocardial injury. Results: Chrysin dose dependently improved ventricular (±LVdP/dtmax and LVEDP) and hemodynamic (SAP, MAP and DAP) dysfunction in isoproterenol-insulted rats. This beneficial effect of chrysin was well supported with increased expression of PPAR-γ and decreased expression of TGF-β as evidenced by western blotting and immunohistochemistry analysis. Moreover, downstream signaling pathway of TGF-β viz. P-ERK½/ERK½ activation and P-JNK/JNK, P-p38/p38 and MMP-2 inhibition were also observed. Chrysin also attenuated NF-κBp65 and IKK-β expressions, TNF-α level and TUNEL positivity thereby validating its anti-inflammatory and anti-apoptotic properties. Additionally, chrysin in a dose dependent fashion improved NO level, redox status of the myocardium (GSH and MDA levels and SOD, GSHPx and CAT activities), cardiac injury markers (CK-MB and LDH levels) and oxidative DNA damage marker (8-OHdG level) and displayed preservation of subcellular and ultrastructural components. Conclusion: We established that activation of PPAR-γ and inhibition of TGF-β via MAPKs dependent mechanism is critical for cardioprotective effect of chrysin. [ABSTRACT FROM AUTHOR]

Heart failure is a leading cause of death of people in South Asia, and cardiomyopathy is a major cause of heart failure. Myosin binding protein C (MYBPC3) is expressed in the heart muscle, where it regulates the cardiac response to adrenergic stimulation and is important for the structural integrity of the sarcomere. Mutations in the MYBPC3 gene are associated with hypertrophic or dilated cardiomyopathies. A 25-base-pair deletion in intron 32 causes skipping of the downstream exon and is associated with familial cardiomyopathy. To date, this deletion is found primarily in India and South Asia, although it is also found at low frequency in Southeast Asia. In order to better characterise the distribution of this variant, we determined its frequency in 447 individuals from 19 populations, including 10 populations from India and neighbouring populations from Pakistan and Nepal. The deletion frequency is over 8% in some of our Indian samples, and it is not present in any of the populations we sampled outside of India. The differences in the deletion frequencies among populations in India are consistent with patterns of variation previously reported and with patterns we observed among Indian populations based on high-density SNP chip data. Our results indicate that the MYBPC3 deletion is primarily found among Indian populations and that its distribution is consistent with genome-wide patterns of variation in India. [ABSTRACT FROM AUTHOR]

Chaudhary and colleagues observed associations of matrix metalloproteinase ( MMP) -2 (-1306C/T) and MMP-9 (-1562C/T) promoter polymorphisms with head and neck squamous cell carcinoma (HNSCC), but not with oral submucous fibrosis (OSMF) in an Indian population. We suggest that they could carry out a haplotype analysis with their data on MMP-2 genotypes (-1306C/T and -168G/T) and that they consider genotyping the microsatellite -90 (CA)14-24 in the MMP-9 promoter region in order to perform haplotype analysis in combination with their data on MMP-9 (-1562C/T) polymorphism. These suggestions could provide additional information with clinical relevance to cancer susceptibility. [ABSTRACT FROM AUTHOR]

• There is a distinct systemic inflammatory profile in pediatric TB. • Plasma levels of MMP-7, LBP and CRP distinguish pulmonary from extrapulmonary TB. • Biological sex influences the inflammatory profile of pediatric TB. The immune profile associated with distinct clinical forms of tuberculosis (TB) has been extensively described for adult populations. Nevertheless, studies describing immune determinants of pulmonary or extrapulmonary TB (PTB or EPTB, respectively) in children are scarce. Here, we retrospectively assessed plasma levels of several mediators of inflammation in age and sex-matched children from South India presenting with PTB (n = 14) or EPTB (n = 22) as well as uninfected healthy controls (n = 19) to identify biomarkers that could accurately distinguish different TB clinical forms. Furthermore, we performed exploratory analyses testing the influence of sex on the systemic inflammatory profile. The analyses identified a biosignature of 10 biomarkers capable of distinguishing the three clinical groups simultaneously. Machine-learning decision trees indicated that C-reactive protein (CRP), matrix metalloproteinase (MMP)-7 and lipopolysaccharide-binding protein (LBP) were the markers that, when combined, displayed the highest accuracy in identifying the clinical groups. Additional exploratory analyses suggested that the disease signatures were highly influenced by sex. Therefore, sex differentially impacted status of systemic inflammation, immune activation and tissue remodeling in children with distinct clinical forms of TB. Regardless of such nuances related to biological sex, MMP-7, CRP and LBP were strong discriminators of active TB and thus could be considered as biomarkers useful in discrimination different TB clinical forms. These observations have implications on our understanding of the immunopathology of both clinical forms of TB in pediatric patients. If validated by other studies in the future, the combination of identified biomarkers may help development of point-of-care diagnostic or prognostic tools. [ABSTRACT FROM AUTHOR]

In heart failure, sympathetic overdrive is evidenced by norepinephrine spillover, receptor level changes, etc. Beta-blockers continue to be the cornerstone of treatment in patients with chronic heart failure due to their ability to counteract sympathetic overdrive. Extensive clinical research has demonstrated that long-term beta-blocker treatment with metoprolol succinate, carvedilol, or bisoprolol enhances left ventricular function and reverses left ventricular remodeling, decreases hospitalization risk, and increases survival. The aim of this consensus paper is to identify patient profiles, initiation or up-titration of beta-blockers and benefits of chirally pure beta-blocker in patients with heart failure. This expert consensus will ensure precise implementation of beta-blockers in heart failure as a part of guideline-directed medical therapy., (© Journal of the Association of Physicians of India 2024.)