Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. METHOD: We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. RESULTS: We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. CONCLUSION: Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

Impact of Atrial Fibrillation on Outcomes in Patients Hospitalized With Nontraumatic Intracerebral Hemorrhage.

Objective: To assess the effect of atrial fibrillation (AF) on outcomes in hospitalizations for non-traumatic intracerebral hemorrhage (ICH). Patients and Methods: We queried the National Inpatient Sample database between January 1, 2016, and December 31, 2019, to identify hospitalizations with an index diagnosis of non-traumatic ICH using ICD-10 code I61. The cohort was divided into patients with and without AF. Propensity score matching was used to balance the covariates between AF and non-AF groups. Logistic regression was used to analyze the association. All statistical analyses were performed using weighted values. Results: Our cohort included 292,725 hospitalizations with a primary discharge diagnosis of non-traumatic ICH. From this group, 59,005 (20%) recorded a concurrent diagnosis of AF, and 46% of these patients with AF were taking anticoagulants. Patients with AF reported a higher Elixhauser comorbidity index (19.8±6.0 vs 16.6±6.4; P<.001) before propensity matching. After propensity matching, the multivariate analysis reported that AF (aOR, 2.34; 95% CI, 2.26-2.42; P<.001) and anticoagulation drug use (aOR, 1.32; 95% CI, 1.28-1.37; P<.001) were independently associated with all-cause in-hospital mortality. Moreover, AF was significantly associated with respiratory failure requiring mechanical ventilation (odds ratio, 1.57; 95% CI, 1.52-1.62; P<.001) and acute heart failure (odds ratio, 1.26; 95% CI, 1.19-1.33; P<.001) compared with the absence of AF. Conclusion: These data suggest that non-traumatic ICH hospitalizations with coexistent AF are associated with worse in-hospital outcomes such as higher mortality and acute heart failure.

Safety of catheter ablation for atrial fibrillation in patients with cancer: a nationwide cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with cancer, especially breast, gastrointestinal, respiratory, urinary tract, and hematological malignancies. Catheter ablation (CA) is a well-established, safe treatment option in healthy patients; however, literature regarding safety of CA for AF in patients with cancer is limited and confined to single centers. OBJECTIVE: We aimed to assess the outcomes and peri-procedural safety of CA for AF in patients with certain types of cancer. METHODS: The NIS database was queried between 2016 and 2019 to identify primary hospitalizations with AF and CA. Hospitalizations with secondary diagnosis of atrial flutter and other arrhythmias were excluded. Propensity score matching was used to balance the covariates between cancer and non-cancer groups. Logistic regression was used to analyze the association. RESULTS: During this period, 47,765 CA procedures were identified, out of which 750 (1.6%) hospitalizations had a diagnosis of cancer. After propensity matching, hospitalizations with cancer diagnosis had higher in-hospital mortality (OR 3.0, 95% CI 1.5-6.2, p = 0.001), lower home discharge rates (OR 0.7, 95% CI 0.6-0.9, p < 0.001) as well as other complications such as major bleeding (OR 1.8, 95% CI 1.3-2.7, p = 0.001) and pulmonary embolism (OR 6.1, 95% CI 2.1-17.8, p < 0.001) but not associated with any major cardiac complications (OR 1.2, 95% CI 0.7-1.8, p = 0.53). CONCLUSION: Patients with cancer who underwent CA for AF had significantly higher odds of in-hospital mortality, major bleeding, and pulmonary embolism. Further larger prospective observational studies are needed to validate these findings.

Inpatient cardiovascular outcomes in patients with cancer affected by viral influenza infection.

BACKGROUND: Influenza disproportionately affects individuals with underlying comorbidities. Long-term follow-up studies have shown that patients with cancer with influenza have higher mortality. However, very little is known about the in-hospital mortality and cardiovascular outcomes of influenza infection in cancer hospitalisations. METHODS: We compared the in-hospital mortality and cardiovascular outcomes in patients with cancer with and without influenza by screening the National Inpatient Sample from 2015 to 2017. A total of 9 443 421 hospitalisations with any cancer were identified, out of which 14 634 had influenza while 9 252 007 did not. A two-level hierarchical multivariate logistic regression analysis adjusted for age, sex, race, hospital type and relevant comorbidities was performed. RESULTS: The group with cancer and influenza had higher in-hospital mortality (OR 1.08; 95% CI 1.003 to 1.16; p=0.04), acute coronary syndromes (OR 1.74; 95% CI 1.57 to 1.93; p<0.0001), atrial fibrillation (OR 1.24; 95% CI 1.18 to 1.29; p<0.0001) and acute heart failure (OR 1.41; 95% CI 1.32 to 1.51; p<0.0001). CONCLUSION: Patients with cancer affected by influenza have higher in-hospital mortality and a higher prevalence of acute coronary syndrome, atrial fibrillation and acute heart failure.

Low left atrial appendage emptying velocity is a predictor of atrial fibrillation recurrence after catheter ablation.

BACKGROUND: Recurrence of atrial fibrillation (AF) after catheter ablation (CA) remains common and studies have shown about 5%-9% annual recurrence rate after CA. We sought to assess the echocardiogram derived left atrial appendage (LAA) emptying velocity as a predictor of AF recurrence after CA. OBJECTIVE: To determine if LAA emptying is a marker of recurrence of AF post-CA METHODS: A total of 303 consecutive patients who underwent CA for AF between 2014 and 2020 were included. Baseline clinical characteristics and echocardiographic data of the patients were obtained by chart review. LAA emptying velocities were obtained from transesophageal echocardiogram (TEE). LA voltage was obtained during the mapping for CA. Chi-square test and nominal logistic regression were used for statistical analysis. An receiver operator characteristic curve was used to determine LAA velocity cut-off. RESULTS: Mean patient age was 61.7 ± 10.5; 32% were female. Mean LAA emptying velocity was 47.5 ± 20.2. A total of 103 (40%) patients had recurrence after CA. In the multivariable model, after adjusting for potential confounders, LAA emptying velocity of ≥52.3 was associated with decreased AF recurrence postablation (odds ratio [OR]: 0.55; 95% confidence interval  [CI]: 0.31-0.97; p = .03*). There were 190 (73%) patients in normal sinus rhythm during TEE and CA, and sensitivity analysis of these patients showed that LAA velocity ≥52.3 remained associated with decreased AF recurrence (OR: 0.35; 95% CI: 0.15-0.82; p = .01*). CONCLUSION: LAA emptying velocity measured during preprocedural TEE can serve as a predictor of AF recurrence in patients undergoing CA.

Can glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors help in mitigating the risk of atrial fibrillation in patients with diabetes?

The role of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in mitigating the risk of atrial fibrillation (AF) remains unknown. We interrogated the Food and Drug Administration's Adverse Event Reporting System (FAERS) database to study the association between AF-related adverse events and the use of GLP-1 RA and DPP-4i. A signal of disproportionate reporting of AF was detected with the DPP-4i group compared with all the other drugs in the FAERS database [ROR, 2.56; 95% confidence interval (CI), 2.10-3.12], whereas there was no disproportionality signal detected with the GLP-1 RA group (ROR, 0.90; 95% CI, 0.78-1.03) although liraglutide showed a significant disproportionality signal (ROR, 2.51; 95% CI, 2.00-3.15). Our analysis supports the existing body of literature demonstrating the cardiac safety of GLP-1 RA but raises concerns about the apparent increase in the risk of AF associated with DPP-4i. Further clinical and translational studies are needed to validate these findings.

Anti-cancer Drugs Associated Atrial Fibrillation-An Analysis of Real-World Pharmacovigilance Data.

Background: Several anti-cancer drugs have been linked to new onset atrial fibrillation (AF) but the true association of these drugs with AF is unknown. The FDA Adverse Event Reporting System (FAERS), a publicly available pharmacovigilance mechanism provided by the FDA, collects adverse event reports from the United States and other countries, thus providing real-world data. Objectives: To identify anti-cancer drugs associated with AF using the FAERS database. Methods: The FAERS database was searched for all drugs reporting AF as an adverse event (AE). The top 30 anti-cancer drugs reporting AF cases were shortlisted and analyzed. Proportional reporting ratio (PRR) was used to measure disproportionality in reporting of adverse events for these drugs. Results: When analyzed for AF as a percentage of all reported AE for a particular drug, Ibrutinib had the highest percentage (5.3%) followed distantly by venetoclax (1.6%), bortezomib (1.6%), carfilzomib (1.5%), and nilotinib (1.4%). The percentage of cardiac AE attributable to AF was also highest for ibrutinib (41.5%), followed by venetoclax (28.4%), pomalidomide (23.9%), bortezomib (18.2%), and lenalidomide (18.2%). Drugs with the highest PRR for AF included ibrutinib (5.96, 95% CI= 5.70-6.23), bortezomib (1.65, 95% CI = 1.52-1.79), venetoclax (1.65, 95% CI = 1.46-1.85), carfilzomib (1.53, 95% CI = 1.33-1.77), and nilotinib (1.46, 95% CI = 1.31-1.63). Conclusions: While newer anti-cancer drugs have improved the prognosis in cancer patients, it is important to identify any arrhythmias they may cause early on to prevent increased morbidity and mortality. Prospective studies are needed to better understand the true incidence of new onset AF associated with anti-cancer drugs.