Cardiac Myosin Inhibitors: Expanding the Horizon for Hypertrophic Cardiomyopathy Management.

OBJECTIVE: To review the current literature on the efficacy and safety of cardiac myosin inhibitors (CMIs) for the treatment of hypertrophic cardiomyopathy (HCM). DATA SOURCES: A literature search was conducted on PubMed from origin to April 2023, using the search terms "MYK-461," "mavacamten," "CK-3773274," and "aficamten." Studies were limited to English-based literature, human subjects, and clinical trials resulting in the inclusion of 13 articles. ClinicalTrials.gov was also used with the same search terms for ongoing and completed trials. STUDY SELECTION AND DATA EXTRACTION: Only phase II and III studies were included in this review except for pharmacokinetic studies that were used to describe drug properties. DATA SYNTHESIS: CMIs enable cardiac muscle relaxation by decreasing the number of myosin heads that can bind to actin and form cross-bridges. Mavacamten, the first Food and Drug Administration (FDA)-approved drug in this class, has been shown to improve hemodynamic, functional, and quality of life measures in HCM with obstruction. In addition, aficamten is likely to become the next FDA-approved CMI with promising phase II data and an ongoing phase III trial expected to release results in the next year. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: CMIs provide a novel option for obstructive hypertrophic cardiomyopathy, particularly in those not suitable for septal reduction therapy. Utilization of these agents requires knowledge of drug interactions, dose titration schemes, and monitoring parameters for safety and efficacy. CONCLUSIONS: CMIs represent a new class of disease-specific drugs for treatment of HCM. Cost-effectiveness studies are needed to delineate the role of these agents in patient therapy.

A multidisciplinary approach to prolonged extracorporeal membrane oxygenation for acute respiratory distress syndrome due to coronavirus 2019-case report.

Patients with novel coronavirus 2019 (COVID-19) may develop acute respiratory distress syndrome (ARDS) and require extracorporeal membrane oxygenation (ECMO) support. Currently there is no specific treatment for COVID-19 available; thus, for patients with severe ARDS, the respiratory condition needs to improve while on ECMO support. Here we present a multidisciplinary team approach to the care of a patient with COVID-related ARDS requiring three months of veno-venous (VV) ECMO which lead to recovery. A 35-year-old male was transferred to us with ARDS due to COVID-19 infection with a lactate 13.7 mmol/L and an arterial-blood gas oxygenation of 75 mmHg on maximum ventilator settings. He was placed on VV ECMO during which he developed pneumonia, bacteremia, and pneumothoraces; however, his other organ functions were preserved. During his time in the Intensive Care Unit (ICU), multiple subspecialist teams participated in his care including physicians, pharmacists, nurses, nutritionists, case management, and social work. The VV ECMO was weaned off after 91 days of support, after which he had a prolonged hospital course due to inflammatory bowel disease, and aspiration pneumonia. CT scan performed six weeks prior to discharge showed mild improvement in diffuse airspace opacities superimposed on extensive chronic cystic changes. He was eventually discharged to a rehabilitation facility 68 days after ECMO removal. He was then seen in our outpatient pulmonary clinic one month and our Post-Intensive Care Syndrome clinic three months after discharge on two liters of nasal cannula oxygen. Pulmonary function testing done at this time demonstrated severe restrictive lung disease and severely reduced diffusion capacity. This case highlights the need for multidisciplinary collaboration among hospital teams to ensure success and patient survival in the setting of COVID ARDS. In those COVID ARDS patients with intact renal, metabolic, hematologic, and cardiovascular function, ECMO should be strongly considered.