Cardiomyopathy, Hypertrophic ; diagnosis ; therapy ; Humans

Cardiomyopathy, Hypertrophic ; diagnosis ; therapy ; Humans

Cardiomyopathy, Hypertrophic ; diagnosis ; therapy ; Consensus ; Humans

Hypertrophy cardiomyopathy (HCM) is an autosomal dominant disorder characterized by increased heart mass that occurs without a defined stimulus (such as hypertension or valvular disease). It is commonly recognized through the widespread use of non-invasive imaging. Epidemiological studies indicate that 1 of 500 individuals has unexplained cardiac hypertrophy, an observation that predicts a considerable role for genetics in this enigmatic disorder. Indeed, to date, more than 500 mutations had been identified in more than 12 genes encoding components of the thick and thin filament of the sarcomere and other myofilament-related proteins. Intensive studies of HCM continue to take our understandings about this fascinating disease in new directions. Mechanistic analyses have provided insights into how mutational alterations in these structural proteins may trigger the hypertrophic remodeling processes and other associated clinical features of HCM. Based on these studies, investigations have been initiated to assess whether early pharmacological interventions could prevent or attenuate the development of the disease and its clinical sequelae. By combining pathophysiology with knowledge of genetic cause and molecular responses, HCM has begun to exemplify opportunities for predictive and personalized medicine. With the emergence of newer technologies that enable high-throughput sequencing of DNA, it is timely to review clinical manifestations and genetic causes of this unique disease, and how intertwining these insights can improve contemporary diagnosis and management of HCM and other genetic forms of cardiac hypertrophy.
Cardiomyopathy, Hypertrophic ; diagnosis ; genetics ; pathology ; therapy ; Humans

Patients with hypertrophic cardiomyopathy who experience refractory symptoms due to left ventricular outflow tract obstruction are often referred for definitive therapy consisting of either surgical myectomy or alcohol septal ablation (ASA). There currently exists clinical equipoise regarding which therapy is the most efficacious in this challenging patient population. ASA utilizes common interventional techniques usually employed to treat atherosclerotic coronary artery disease to inject small aliquots of ethanol into a branch of the appropriate septal vessel to cause necrosis of the obstructing basal septal tissue. Myocardial contrast echocardiography is used to facilitate location of the most appropriate septal branch with success determined by an acute reduction in the resting and/or provoked gradient. Recent comparative data have suggested similar rates of long and short-term mortality in when comparing patients undergoing ASA and surgical myectomy, with ASA patients experiencing a higher rate of requirement for permanent pacemakers. In addition, patients treated by both techniques appear to have similar gradient reductions and improvement in symptomatic status. Comparisons of these two methods of treatment are limited by the non-randomized nature of the studies, retrospective data collection and the allocation of higher-risk patients to ASA treatment. Concern for the wide-spread adoption of ASA to drug-resistant HCM patients is warranted due to the potential for arrhythmogenesis is a patient population already at risk for life-threatening arrhythmias. There have been case reports of such arrhythmias, however, clinical series to date have not suggested an enhanced risk of sudden cardiac death in patients treated with ASA. Definitive answers concerning which patient subsets with drug-refractory hypertrophic cardiomyopathy would benefit from the two competing therapies can only be answered by a randomized clinical trial. However, for a variety of clinical and logistical factors, such a trial is unlikely to ever be performed. For the foreseeable future, patient-specific therapy will depend on local expertise, patient comorbidities and preferences.
Cardiomyopathy, Hypertrophic ; therapy ; Catheter Ablation ; methods ; Ethanol ; therapeutic use ; Humans

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with hypertrophic cardiomyopathy (HCM), and represents an important complication in the clinical course of the disease, with adverse consequences on functional status and outcome. Studies on community-based HCM patient populations have shown that AF is associated with long-term clinical deterioration, cardioembolic stroke and increased cardiovascular mortality due to heart failure and stroke. Moreover, acute onset of AF may cause severe hemodynamic impairment and represent a trigger of potentially lethal ventricular arrhythmias. However, the consequences of AF on the long-term prognosis of HCM patients are not uniformly unfavorable, and may be compatible with an uneventful course, when properly managed. Management of AF in HCM is challenging, particularly when onset occurs at a young age. Both paroxysmal and permanent AF represent clear indications for oral anticoagulation. In most patients, maintenance of sinus rhythm is highly desirable but made difficult by the limited long-term efficacy and potentially hazardous side effects of available pharmacological options. In selected patients with HCM and severely symptomatic AF, radiofrequency catheter ablation may represent an effective therapeutic alternative, improving functional status, and reducing or postponing the need for antiarrhythmic drugs. In patients with persistent AF, in whom maintenance of sinus rhythm is not feasible, adequate ventricular rate control should be pursued aggressively by atrio-ventricular node blocking agents.
Atrial Fibrillation ; epidemiology ; therapy ; Cardiomyopathy, Hypertrophic ; epidemiology ; therapy ; Humans ; Incidence ; Prognosis ; Risk Assessment

Benzylamines ; Cardiomyopathy, Hypertrophic/drug therapy* ; Humans ; Pharmaceutical Preparations ; Uracil/analogs & derivatives*

Nonsurgical septal reduction by coil embolisation of the first major septal branch was successfully performed in a 34-year-old patient with hypertrophic obstructive cardiomyopathy, resulting in acute reduction of left ventricular outflow tract obstruction and symptomatic improvement. Follow-up at 18 months showed sustained clinical and echocardiographic benefits from the procedure. To the best of our knowledge, this is the first case reported in Singapore.
Adult ; Cardiomyopathy, Hypertrophic ; therapy ; Diagnostic Imaging ; Embolization, Therapeutic ; methods ; Heart Septum ; Humans ; Male

Animals ; Cardiomyopathy, Hypertrophic ; drug therapy ; physiopathology ; Disease Models, Animal ; Enalapril ; pharmacology ; therapeutic use ; Rabbits ; Ventricular Remodeling

Cardiomyopathy, Hypertrophic/diagnostic imaging* ; Endocarditis/diagnosis* ; Endocarditis, Bacterial/drug therapy* ; Humans