Nouraee, Cyrus

ABSTRACT Introduction Cardiac myosin inhibitors (CMIs) improve hemodynamics and symptoms in hypertrophic cardiomyopathy (HCM), but recent real‐world data have raised concerns regarding an increased risk of atrial fibrillation (AF). We sought to reassess AF risk using randomized controlled trial (RCT) evidence and to contextualize discrepancies with observational reports. Methods and Results We performed a systematic review and random‐effects meta‐analysis of RCTs evaluating the effect of CMIs on incident AF in HCM. MEDLINE, Scopus, and CENTRAL were searched through November 25, 2025. Eight RCTs ( n = 1581) comparing mavacamten or aficamten with placebo or active control were included. Event counts were pooled as risk ratios (RRs) with 95% confidence intervals (CIs). CMIs were not associated with increased AF risk (RR 1.11, 95% CI 0.62–1.98; heterogeneity I 2 = 0%). No differences were observed between mavacamten and aficamten, with consistent findings across HCM subtypes (obstructive and non‐obstructive). Importantly, most trials (7/8) excluded patients with uncontrolled, persistent, or permanent AF, five excluded paroxysmal AF at screening, and one excluded any AF history. Baseline left atrial enlargement was generally in the mild to moderate range across trials, suggesting limited representation of high‐risk AF phenotypes. Conclusion Randomized evidence to date does not demonstrate an increased AF risk with CMIs. Differences between RCT populations and real‐world cohorts, including restrictive AF eligibility criteria, lower baseline atrial remodeling, and limited rhythm surveillance may explain discordant observational findings and highlight the need for longitudinal monitoring in clinical practice.

Kounis syndrome (KS) is a dangerous and rare acute coronary syndrome elicited in the setting of an allergic, hypersensitivity, or anaphylactic reaction. The syndrome is caused by mast cell activation leading to a release of proinflammatory mediators that can promote coronary vasospasm, atheromatous plaque erosion with rupture, or both. We present the case of a 48-year-old female with a past medical history of type 2 diabetes, hypertension, and chronic kidney disease stage 3 who presented via ambulance with anaphylaxis following an unknown allergen exposure. She was immediately given intramuscular epinephrine with resolution of symptoms, but she continued to have chest discomfort with radiation to her back. Initial EKG showed deep ST depressions in numerous leads (mainly the inferior and anterolateral leads) with ST elevations in leads V1 and aVR, consistent with diffuse subendocardial ischemia (Figure 1). Initial troponin was 2,122 which peaked at 5,328. Coronary angiogram was immediately obtained which showed patent coronary arteries with minimal narrowing of the distal left anterior descending artery. Because of this, cardiac MRI was obtained which showed subendocardial delayed enhancement at the basal and mid left ventricle with associated subendocardial perfusion defects and myocardial edema. These were felt to be in the distributions of the left circumflex and left anterior descending arteries and likely due to vasospasm, so the patient was initiated on diltiazem. Allergy evaluated the patient and felt her symptoms represented KS. They recommended outpatient workup to identify an allergy trigger and discharge with an epinephrine pen. KS is a rare presentation of acute coronary syndrome in the setting of an allergic, hypersensitivity, or anaphylactic reaction. Clinicians must be aware of this phenomenon to be able to promptly diagnose and evaluate these patients as late diagnosis can lead to significant morbidity and mortality.