Nitish Behary Paray

Incretin-based dual and triple agonists have emerged as effective options for obesity management, offering enhanced weight loss through multi-receptor agonism. However, data on their efficacy and safety remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these emerging agents. A comprehensive literature search was conducted using PubMed, the Cochrane Library, and Google Scholar from inception to June 2025 to identify randomized controlled trials evaluating tirzepatide, retatrutide, or mazdutide in obese adults. Clinical outcomes were assessed using the random‐effects model and pooled as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). A total of 10 randomized controlled trials, including 3236 participants, were analyzed. Incretin polyagonists significantly reduced body weight compared to placebo (MD −11.47; 95% CI: −14.00 to −8.95). Significant reductions were also observed in waist circumference (MD −9.40; 95% CI: −11.91 to −6.89), glycated hemoglobin (MD −0.96; 95% CI: −1.16 to −0.75), and fasting plasma glucose (MD −26.89 mg/dL; 95% CI: −33.48 to −20.30). However, the use of dual and triple agonists was associated with a higher risk of any adverse events (AEs) (RR 1.13; 95% CI: 1.08–1.19), including gastrointestinal AEs (nausea, vomiting, diarrhea, constipation), AEs leading to withdrawal (RR 1.96; 95% CI: 1.17–3.30), and hypoglycemic episodes (RR 3.08; 95% CI: 1.61–5.89). No significant difference was found in serious AEs (RR 0.87; 95% CI: 0.65–1.14). In conclusion, incretin-based polyagonists were associated with significant weight reduction and improved metabolic outcomes compared to placebo.

Background: Hypertension remains a major contributor to global cardiovascular morbidity and mortality. Aldosterone, a key hormone in blood pressure regulation, plays a significant role in hypertension pathophysiology. This has led to growing interest in aldosterone synthase inhibitors (ASIs) as a potential treatment. This meta‐analysis aims to evaluate the efficacy and safety of ASIs in managing hypertension. Methods: A systematic search of PubMed, Google Scholar and Cochrane Central was conducted up to 13 July 2025, to identify randomised controlled trials (RCTs) evaluating ASIs in hypertensive adults. Data were analysed using RevMan version 5.4, employing random‐effects models with significance set at p < 0.05. Results: A total of 8 RCTs were included, with a total of 2003 participants in the ASI group and 650 participants in the placebo group. ASIs significantly reduced systolic blood pressure (SBP) compared to placebo (MD: −6.01 mmHg; 95% confidence interval [CI]: −9.31 to −2.71; I ² = 85%; p = 0.0004); diastolic blood pressure (DBP) was found to be comparable between the two groups (MD: −2.20 mmHg; 95% CI: −4.46 to 0.06; I ² = 69%; p = 0.06). There was a significant reduction in serum aldosterone levels favouring ASI use (MD: −1.46; 95% CI: −2.76 to −0.16; I ² = 99%; p < 0.00001). The risk of serious (RD: 0.00; 95% CI: −0.01 to 0.02; I ² = 30%; p = 0.75) and non‐serious adverse events (RD: 0.05; 95% CI: −0.02 to 0.12; I ² = 64%; p = 0.20) did not differ significantly between ASI and placebo groups. However, ASI use was associated with a significantly higher risk of hyperkalemia (RD: 0.04; 95% CI: 0.02 to 0.06; I ² = 70%; p = 0.002). Conclusion: ASIs effectively lower SBP and serum aldosterone in adults with hypertension. They appear safe overall but may increase the risk of hyperkalemia.

Introduction: Isolated cardiac sarcoidosis (ICS) is characterized by a lack of the apparent extra-cardiac involvement seen in systemic cardiac sarcoidosis (SCS) and is being increasingly recognized as a distinct clinical phenotype of cardiac sarcoidosis. This systematic review and meta-analysis pooled data from published literature to assess any differences in outcomes of ICS vs. SCS patients.Material and methods: Studies were identified from PubMed/Medline, Embase, and the Cochrane Library. Risk ratios were calculated using the Mantel-Haenszel method in a random effects model. Heterogeneity was assessed using the Higgins I2 statistic. Leave-one-out sensitivity analysis was also performed. The primary outcome was a composite of MACE, including cardiac death, ventricular arrhythmias, or hospitalization for heart failure. The secondary outcomes included sudden cardiac death, arrhythmias, and heart-failure-related hospitalizations.Results: The analysis included 7 studies and 918 CS patients (28.9% ICS and 71.1% SCS). Increased risk for arrhythmias (RR = 3.06, 95% CI: 0.98 to 9.55, p = 0.05, I2 = 67%) in patients with ICS compared to SCS was observed. No significant difference was observed for composite outcome (RR = 1.43, 95% CI: 0.93 to 2.18, p = 0.10, I2 = 0%), HF-related hospitalizations (RR = 6.83, 95% CI: 0.47 to 100.33, p = 0.16, I2 = 80%), or cardiac death (RR = 1.85, 95% CI: 0.49 to 7.08, p = 0.37, I2 = 0%) between the two groups.Conclusions: Although ICS patients were more likely to experience arrhythmias, no significant difference was observed between ICS and SCS patients for composite outcome, cardiac death, or hospitalizations due to heart failure.

Background: Acute myocardial infarction (AMI) remains a leading cause of mortality in the USA, particularly among individuals aged 65 and older. There is limited research about the association between psychoactive substance use and cardiovascular death due to AMI. This study aims to analyze trends in AMI‐related mortality among older adults (aged ≥ 65) associated with psychoactive substance use in the USA from 1999 to 2020, with a focus on demographic and geographic variations.Methods: We conducted a descriptive analysis using death certificates from the CDC's WONDER database. Data were extracted for age, sex, race/ethnicity, urban–rural status, and geographic region. Crude mortality rates and AAMR were calculated, and temporal trends were assessed using Joinpoint regression.Results: Between 1999 and 2020, there were 231 359 AMI‐related deaths among older adults with substance use disorders. Men (39.2) had a markedly higher mortality rate than women (15.0). Mortality rates increased across all age groups, with the most pronounced rise in those aged 85 and older (33.9). Metropolitan areas (22.3) experienced lower mortality rates than nonmetropolitan areas (37.9). The Midwest (32.3) consistently recorded the highest mortality rates, followed by the Northeast (25.0), South (24.5), and West (18.7).Conclusion: The study reveals notable temporal trends in AMI mortality among older adults with psychoactive substance use, highlighting significant demographic and regional disparities. These findings underscore the need for targeted interventions to address this growing public health issue.

While studies confirm the feasibility of percutaneous mitral valve repair, its short- and long-term outcomes compared with mitral valve surgery remain debated. This meta-analysis aims to evaluate the clinical outcomes with a percutaneous approach and surgery. A comprehensive literature search of major databases that included PubMed, Embase, and the Cochrane Library was performed from inception to November 2024. Randomized controlled trials (RCTs) and propensity-adjusted observational studies that reported clinical outcomes following percutaneous mitral valve repair versus mitral valve surgery in patients with mitral regurgitation were included in the review. The pooled estimates were calculated using a random effects model. A total of 6 studies (n = 5411 patients) were included. The pooled analysis demonstrated no statistically significant difference between the 2 approaches for all-cause death at 1 month [risk ratio (RR) = 1.13, 95% confidence interval (CI): 0.54–2.37], and 1 year (RR = 1.98, 95% CI: 0.91–4.32). The risk of stroke was significantly reduced in the percutaneous group (RR = 0.42, 95% CI: 0.23–0.74); however, the pooled estimates remained comparable for hospitalization for heart failure (RR = 0.88, 95% CI: 0.38–2.04), all-cause rehospitalization (RR = 1.03, 95% CI: 0.55–1.95), sepsis (RR = 0.25, 95% CI: 0.06–1.13), atrial fibrillation (RR = 0.44, 95% CI: 0.10–2.06), and Grade 3+ or 4+ mitral regurgitation (RR = 3.02, 95% CI: 0.74–12.37). Compared with surgery, the percutaneous approach demonstrates a similar safety profile and a reduced risk of stroke. However, long-term mortality is comparable between the 2 techniques, indicating that a patient-tailored approach will lead to optimal results.

Background and Objectives: The epidemiological data regarding mortality rates of adults with sarcoidosis and non-ischemic cardiovascular disease (CVD) are limited. A retrospective observational analysis was conducted to identify trends and disparities related to sarcoidosis and non-ischemic cardiovascular disease mortality among the adult US population from 1999 to 2022. Methods: We used the Centers for Disease Control and Prevention (CDC) WONDER database to extract death certificate data for the adult US population (≥25 years). The age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and annual percent changes (APCs) were determined using Joinpoint. Results: Between 1999 and 2022, 23,642 deaths were identified related to non-ischemic CVD + sarcoidosis. The overall AAMR increased from 0.2 (95% CI, 0.2 to 0.3) in 1999 to 0.5 (95% CI, 0.5 to 0.6) in 2022. Females had a higher AAMR than males (0.6 vs. 0.5). Non-Hispanic (NH) blacks had the highest AAMR, followed by NH whites and Hispanic or Latinos. The southern region had the highest AAMR (0.7: 95% CI, 0.6–0.7), followed by the Midwest (0.6, 95% CI, 0.54–0.669), the Northeast (0.5, 95% CI, 0.5 to 0.6), and the West (0.4; 95% CI, 0.3–0.4). Urban and rural areas had comparable mortality rates (0.5 vs. 0.6). People aged 65+ had the highest AAMRs. Conclusions: The overall mortality rates for non-ischemic CVD and sarcoidosis have increased in the US from 1999 to 2022. Females and NH blacks had higher AAMRs, while a minimal variation was observed based on geographical regions. Early diagnosis and prompt management are the keys to reducing the mortality burden of non-ischemic CVD plus sarcoidosis.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by structural and functional abnormalities. Current management strategies, such as medications and septal reduction therapies, have significant limitations and risks. Recently, cardiac myosin inhibitors (CMIs) like mavacamten and aficamten have shown promise as noninvasive treatment options. This meta-analysis aims to evaluate the efficacy and safety of CMIs in HCM patients. PubMed/MEDLINE, Embase, the Cochrane Library, Ovid, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared CMIs to control treatments in HCM patients from inception till June 15, 2024. A random-effects model was used to pool odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes along with the corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the χ² test and Higgins I ² statistic, and sensitivity and subgroup analyses were performed. Six RCTs involving 826 patients were included. CMI therapy significantly reduced resting left ventricular outflow tract (LVOT) gradient (MD, −37.64; 95% CI, −46.71 to −28.56), Valsalva LVOT gradient (MD, −46.04; 95% CI, −57.60 to −34.48), post-exercise LVOT peak gradient (MD, −48.64; 95% CI, −68.20 to −28.88), N-terminal pro-b-type natriuretic peptide levels (MD, −1.05; 95% CI, −1.64 to −0.47), and cardiac troponin I levels (MD, −7.96; 95% CI, −12.84 to −3.07). Improvements were observed in peak oxygen consumption (MD, 1.20; 95% CI, 0.23–2.17) and patient-reported outcomes (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score: MD, 6.44; 95% CI, 3.50–9.37), with more patients achieving New York Heart Association class improvement >1 (OR, 4.05; 95% CI, 2.61–6.30). Treatment-emergent adverse events were higher with CMI therapy (OR, 1.45; 95% CI, 1.02–2.05), but serious adverse events and other safety outcomes were comparable in both groups. CMIs, including mavacamten and aficamten, significantly improve clinical outcomes in HCM patients with a manageable safety profile. These results indicate that CMIs offer a promising noninvasive alternative to septal reduction therapies.

Introduction: Cannabis is increasingly becoming a socially acceptable substance, with multiple countries having legalised its consumption. Epidemiological studies have demonstrated an association between cannabis use and an increased risk of developing coronary artery disease. However, there is a lack of studies about the influence of cannabis consumption on the outcomes following acute myocardial infarction (AMI).Material and methods: We retrospectively analysed hospitalised patients with a primary diagnosis of AMI from the 2001 to 2020 National Inpatient Sample (NIS). Pearson’s X2 tests were applied to categorical variables, and t-tests for continuous variables. We conducted a 1:1 propensity score matching (PSM). Multivariate regression models were deployed on the PSM sample to estimate the differences in several events and all-cause mortality.Results: A total of 9,930,007 AMI patients were studied, of whom 117,641 (1.2%) reported cannabis use. Cannabis users had lower odds of atrial fibrillation (aOR = 0.902, p < 0.01), ventricular fibrillation (aOR = 0.919, p < 0.01), cardiogenic shock (aOR = 0.730, p < 0.01), acute ischaemic stroke (aOR = 0.825, p < 0.01), cardiac arrest (aOR = 0.936, p = 0.010), undergoing PCI (aOR = 0.826, p < 0.01), using IABP (aOR = 0.835, p < 0.01), and all-cause mortality (aOR = 0.640, p < 0.01), but with higher odds of supraventricular tachycardia (aOR = 1.104, p < 0.01), ventricular tachycardia (aOR = 1.054, p < 0.01), CABG use (aOR = 1.040, p = 0.010), and acute kidney injury (aOR = 1.103, p < 0.01).Conclusions: Among patients aged 18–80 years admitted to hospital with AMI between 2001 and 2020 in the United States, cannabis use was associated with lower risks of cardiogenic shock, acute ischaemic stroke, cardiac arrest, PCI use, and in-hospital mortality.

Background : In the multiple trials that established the efficacy of implantable cardiac defibrillator (ICD) in preventing sudden cardiac death, patients aged ≥ 80 years were poorly represented. One aspect of the paucity of data on outcomes in this subgroup pertains to any difference in survival based on the indication for the device, i.e. primary vs secondary prevention of ventricular arrhythmias. Methods : We performed a monocentric retrospective observational study of octogenarians receiving ICD therapy over a twelve-year period (n=95). Fisher exact and Chi-squared tests were used for categorical variables and student t-test and Wilcoxon rank-sum for continuous variables. A Kaplan-Meier survival analysis using logrank test and an adjusted Cox regression Hazard Ratio model was performed to compare survival between primary and secondary prevention groups. Results : Mean age of the cohort was 83.1 ± 3 years, with 85% (n=81) being male. 73% (n=69) of the participants had ischaemic cardiomyopathy and 43% (n=41) met the primary prevention indications. Overall survival at 5 years was 80% with a median survival time post device implantation at 27 months (IQR 12 – 55). The difference in survival rates between primary and secondary prevention was not statistically significant (p=0.63). Inappropriate shocks were delivered in 2 patients while 14 patients were successfully treated with appropriate therapy. Complications were encountered in 9.5% (n=9) of cases. Conclusion : In carefully selected octogenarians, there is no significant difference in the survival benefit conferred by ICD therapy based on the indication for the device. Advanced chronological age alone should not unduly influence the decision for ICD selection. There is an imperative for a greater representation of this cohort in future trials