Precision Management of Hypertrophic Obstructive Cardiomyopathy: A Case Study on Mavacamten with Emphasis on Individualized Dosing and Follow-up

Patient Presentation:

A 53-year-old man presented with severe angina and left arm pain on mild exertion (CCS III), without dyspnea or syncope. Physical examination was normal. His last cardiology visit was four years prior, with coronary angiography performed without intervention 15 years ago. He was on an ACE inhibitor, had mild hypertension, substituted hypothyroidism, and smoked. His symptoms impaired his ability to work.

Initial Work-up:

High-sensitive troponin was elevated (0h: 35; 1h: 32 ng/l). Coronary angiography showed three-vessel disease with LAD stenosis after the second diagonal, chronic occlusion of the first marginal branch with RCA collaterals, and proximal RCA stenosis. Only the LAD stenosis was hemodynamically significant (FFR 0.58) and was treated with a drug-eluting stent. Medications were initiated with aspirin, prasugrel, metoprolol, and atorvastatin. Echocardiography showed severe LV hypertrophy with a dagger-shaped LVOT Doppler signal, indicating LV outflow obstruction. CMR confirmed hypertrophic obstructive cardiomyopathy (HOCM), revealing a maximum septal thickness of 22 mm.

Diagnosis and Management:

In our outpatient clinic, Doppler measurements showed a pressure gradient of 123 mmHg at rest and 152 mmHg under Valsalva. The patient’s sudden cardiac death risk score was 3%, so an ICD was not pursued. Despite uptitrating metoprolol (95 mg b.i.d.), he remained symptomatic, repeatedly visiting the ER due to dyspnea and atypical angina. His initial 6MWD was 186m, indicating limited exercise tolerance. After heart team discussions, the patient was deemed ineligible for TASH, and he declined septal myectomy. With mavacamten’s recent market availability and a CYP2C19 slow metabolizer status identified, the patient started low-dose mavacamten (2.5 mg daily). Novel ESC cardiomyopathy guidelines suggested mavacamten as an option before interventional or surgical therapies (Class IIa Recommendation).

Follow-up:

After four weeks mavacamten therapy, a follow-up showed reduced gradients at rest (13 mmHg) and under Valsalva (21 mmHg), with preserved LVEF (58%) and an improved 6MWD to 419m, with angina symptoms resolved. The initial dose of 2.5 mg daily was continued. However, at the three-month follow-up, symptoms recurred, and LVOT gradients increased again (123 mmHg at rest, 152 mmHg under Valsalva). We increased mavacamten dosage to 5 mg daily, despite the CYP2C19 slow metabolizer status. Three months later, follow-up revealed a sustained low gradient (13 mmHg at rest, 14 mmHg under Valsalva) and stable LV function (LVEF 53%).

Conclusion:

This case underscores the importance of individualized treatment for HOCM. While initial symptoms and risk factors suggested coronary artery disease, diagnostic imaging also revealed HOCM. After unsuccessful symptom control with beta-blockers, interventional and surgical options were considered, but patient preference and individual risk led to mavacamten therapy. Mavacamten, supported by novel ESC guidelines, offered a timely alternative, with initial improvement in symptoms and quality of life. Recurrence of symptoms and elevated gradients after three months highlighted the need for systematic follow-up and dosage adjustment, especially with CYP2C19 pharmacogenetic considerations. Increasing mavacamten to 5 mg daily successfully stabilized symptoms and LVOT gradients.