Hypertrophic cardiomyopathy: A case report
N. Dharsshini
Clinical pharmacy Intern, Kauvery Hospital Cantonment, Trichy
Background
Hypertrophic Cardiomyopathy (HCM) is a multifaceted disorder arising from abnormalities in the cardiac sarcomere, the fundamental unit of heart muscle contraction. This dysfunction leads to an imbalance in cardiac myosin–actin cross-bridging, causing heightened sensitivity to calcium, a vital regulator of muscle contraction and relaxation. Core pathophysiologic features encompass left ventricular hypertrophy (LVH), notably affecting the subaortic region of the interventricular septum. Microvascular ischemia, myocardial fibrosis, and diastolic dysfunction further characterize HCM, collectively contributing to the clinical complexities of this condition.[1],[2],[3]
The primary pathology involves mutations in genes that encode proteins of the cardiac sarcomere, the basic contractile unit of the heart. These mutations lead to disruptions in the normal functioning of the sarcomere, resulting in the hypertrophy (thickening) of the heart muscle. Diagnosis often involves a combination of clinical evaluation, imaging studies (such as echocardiography), and genetic testing. Family screening is also essential due to the hereditary nature of the condition.
Clinical features of this condition include various common symptoms such as fainting, chest pain (angina), palpitations, difficulty breathing when lying flat (orthopnea), sudden nocturnal onset of severe shortness of breath (paroxysmal nocturnal dyspnea), dizziness, congestive heart failure, and, in severe instances, the risk of sudden cardiac death. The predominant presenting symptom of Hypertrophic Cardiomyopathy (HCM) is dyspnea, particularly during physical exertion.
HCM is associated with an increased risk of arrhythmias, including atrial fibrillation and ventricular arrhythmias, which can contribute to complications such as sudden cardiac death. Hypertrophy of the heart muscle, can lead to obstruction of the left ventricular outflow tract. Individuals with HCM may be at an increased risk of developing infective endocarditis, an infection of the inner lining of the heart chambers and valves. In some cases, individuals with HCM may develop features of restrictive cardiomyopathy, where the heart becomes less compliant, affecting its ability to fill with blood properly. The hypertrophy and stiffness of the heart muscle can result in diastolic dysfunction, impairing the heart’s ability to relax and fill with blood during the diastolic phase of the cardiac cycle.
Case Presentation
A 46-year-aged male presented with a four-day history of fever accompanied by continuous sweating. He reported no palpitation, giddiness, loss of consciousness, cough, vomiting, or abdominal pain. Past medical history revealed no Type 2 Diabetes Mellitus (T2DM), systemic hypertension (STN), or dyslipidemia (DLP).
Vitals and Lab Investigations
Laboratory results showed a haemoglobin – 13.8 g/dl, Total leukocytes – 6500 cells/cumm, an elevated ESR – 27, and a C-reactive protein – 43.7 mg/dl. Notably, Widal test and blood culture results were negative.
ECG findings revealed arrowhead T waves in specific leads with marked T-wave inversion in anterior leads. An echocardiogram (ECHO) indicated hypertrophy in apical segments, along with good left ventricular function (EF-60%) and Grade I Diastolic Dysfunction. The comprehensive diagnosis included Apical Hypertrophic Cardiomyopathy, Acute Febrile Illness, and Lower Respiratory Tract Infection.
Impression
ECG shows T wave inversion and left ventricular hypertrophy
Management
Treatment encompassed Inj. Heparin, pantoprazole, cefoperazone sulbactam, Tab. amlodipine, paracetamol, azithromycin, and oseltamivir. The patient positively responded to the prescribed regimen and was discharged with the recommended medications.
Mavacamten: The new drug for HCM
Mavacamten is a selective cardiac myosin inhibitor that targets the underlying hypercontractility seen in Hypertropic cardiomyopathy (HCM), a genetic condition characterized by the thickening of the heart muscle. Mavacamten inhibits cardiac myosin ATPase, leading to a reduction in excessive contraction of the cardiac muscle.[4] The EXPLORER-HCM trial and the MAVERICK-HCM trial are examples of clinical trials that have investigated Mavacamten in patients with hypertrophic cardiomyopathy and improves exercise capacity in patients with obstructive HCM. Mavacamten was well tolerated with no significant long-term treatment-related adverse events [5.]. Mavacamten had received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of symptomatic obstructive HCM in adults.[6]
Mavacamten is typically administered orally. Mavacamten undergoes metabolism primarily through the cytochrome P450 system in the liver, with the involvement of CYP2D6 and CYP3A4 enzymes. It is eliminated through both renal and hepatic routes. Mavacamten has the potential for drug interactions, particularly with medications that are substrates or inhibitors of CYP2D6 or CYP3A4 enzymes. Healthcare providers need to consider these interactions when prescribing mavacamten in combination with other drugs. Common adverse effects include headache, dizziness, and fatigue.
Reference
- Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation 2020;142:558-631.
- Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 2017;121:749-70.
- Lehman SJ, Crocini C, Leinwand LA. Targeting the sarcomere in inherited cardiomyopathies. Nat Rev Cardiol 2022;19:353-63.
- Green EM, Wakimoto H, Anderson RL, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science. 2016;353(6305):46-51.
- Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396(10253):759-769.
U.S. Food and Drug Administration. FDA approves first treatment for obstructive hypertrophic cardiomyopathy. [Press Release].
N. Dharsshini
Clinical Pharmacy – Intern