Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM.

A 66-year-old man was referred to our cardiology unit with worsening shortness of breath on exertion. Electrocardiogram (ECG) showed sinus rhythm, QS complex in leads V1 and V2, and diffuse negative symmetric T-waves (panel A). Echocardiography revealed thickened apical segments with obliteration of the left ventricular cavity and a mobile intraventricular isoechoic mass of 40 × 35 mm (panel B, asterisk). Low-molecular-weight-heparin and warfarin were immediately started. Blood tests documented absolute eosinophil count of 4500/μL. After a thorough workup ruled out causes for secondary eosinophilia, a diagnosis of hypereosinophilic syndrome was suspected. Cardiovascular magnetic resonance imaging documented the presence of relative apical hypertrophy with abnormal basoapical tapering of left ventricular wall thickness, papillary muscle apical displacement, and elongated anterior mitral valve leaflet and revealed major diagnostic criteria of endomyocardial fibrosis with a layer of subendocardial late gadolinium enhancement lining the apical segments of both ventricles with superimposed intracavitary thrombosis (panels C to H, Supplementary material online , Videos S1 and S2). Endomyocardial biopsy obtained from the right ventricular septum confirmed the fibrous thickening of the endocardium and presence of faecal areas of myofibrillar disarray and replacement fibrosis. The patient was discharged on warfarin but declined steroid treatment and genetic testing. Six-month follow-up was uneventful with partial resolution of left ventricular thrombosis. We present a case of dual apical hypertrophic cardiomyopathy and endomyocardial fibrosis pathology in a patient with idiopathic hypereosinophilic syndrome, a rare disorder with frequent cardiac involvement featuring endocardial fibrous tissue proliferation. Treatment is mainly directed towards prevention and management of chronic heart failure, arrhythmia, pulmonary hypertension, and thromboembolic events.

Relative Bradycardia (RB) is a poorly understood condition that refers to inappropriately low heart rate response to a given increase in body temperature. Dysfunctional crosstalk between the immune system and the autonomous nervous system has been advocated. It is most often observed in intracellular gram negative and parasitic infections, with a prevalence ranging between 15% and 20%. The aim of this study was to identify the prevalence, clinical determinants and significance of RB in patients hospitalized for SARS-CoV-2 infection and to evaluate its prognostic value for long-covid syndrome during follow-up. We enrolled consecutive patients hospitalized for SARS-CoV-2 infection from March 2020 to April 2021. We collected clinical parameters including clinostatic and orthostatic blood pressure (BP) and heart rate (HR) at 1,3 and 5 minutes, oxygen saturation, body temperature (BT), routine blood tests, 12-lead ECG, and 48-h Holter ECG. At follow up, clinical symptoms were investigated by novel Malmo POTS Symptoms (MAPS) questionnaire. Total population included 269 inpatients (mean age 67±17 years, 59% male).Of these, 30 (11%) presented with sinus bradycardia and 37 (14%) RB. RB was more frequently observed in younger male patients with higher BT and heightened CRP levels. There were no significant correlations between BP and HR orthostatic changes and BR during hospital admission or during follow-up. No clinically relevant arrhythmias were revealed during 48-hour ECG monitoring. After mean16-month follow-up, MAPS score was higher in patients with RB (30±19) compared to those without RB (18±21, p=0.001) during index hospital admission. Dizziness, palpitations and fatigue were more frequently reported in patients with RB(p<0.001). RB is not an uncommon condition during acute COVID-19. SARS-CoV-2 inpatients who presented RB during index hospitalization showed a higher symptom burden during follow-up, as recorded by MAPS score. Further studies are needed to clarify the clinical significance of RB and its value to predict post-acute sequelae of COVID-19. Spahic et Al., Malmö POTS symptom score: Assessing symptom burden in postural orthostatic tachycardia syndrome JIM 2022 (in press)