Description of Case: A 55-year-old male with a history of paroxysmal atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM) diagnosed three years prior at an outside institution presented to clinic with exertional dyspnea. Baseline TTE confirmed HCM demonstrating an EF of 69%, mitral systolic anterior motion (SAM), left ventricular outflow tract (LVOT) obstruction, and a peak gradient exceeding 100 mmHg. Initiation of mavacamten 5mg resulted in symptom improvement and a one-month follow-up TTE demonstrating a reduced peak gradient of 74 mmHg and normal EF. However, two months after initiation the patient returned with AF with rapid ventricular response (RVR) and TTE showed a newly reduced EF of 21%. Mavacamten was stopped while home metoprolol XL was increased from 100 to 150 mg daily for rate optimization. Holter monitoring showed a 100% Afib burden with an average heart rate of 108 beats per minute. Stopping mavacamten for four weeks resulted in worsening exertional dyspnea but restoration of EF to 52% on TTE. Mavacamten was reinstated at a lower dose of 2.5 mg, resulting in symptom improvement. Monthly TTE exams over four months consistently demonstrated a normal EF without LVOT obstruction at rest. Discussion: Mavacamten, a promising drug used to treat obstructive HCM, modulates myosin to reduce myosin-actin cross-bridging. Reduction in contractility improves mitral SAM, LVOT obstruction, and symptoms. However, because mavacamten is a negative inotrope it can also precipitate reductions in EF. Generally, patients have a mild drop in EF (~5 points) after initiation. However, our patient had a significant EF drop of over 25 points likely due to both mavacamten initiation and new AF with RVR reducing systolic function. Discontinuation of mavacamten for four weeks and rate optimization likely restored EF. Dose reduced re-initiation of mavacamten resulted in long-term normal EF and improvement in symptoms. This case highlights the need for close monitoring and individualized mavacamten treatment plans. Further research is warranted to understand the interplay and long term outcomes of tachyarrhythmias and mavacamten use.