Pathology Results and Genetic Testing

CardioNerds cofounder Dr. Amit Goyal and cardiology fellows from the Cleveland Clinic (Drs. Alejandro Duran Crane, Gary Parizher, and Simrat Kaur) discuss the following case: A 61-year-old man presented with symptoms of heart failure and left ventricular hypertrophy. He was given a diagnosis of obstructive hypertrophic cardiomyopathy. He eventually underwent septal myectomy, mitral valve replacement, aortic aneurysm repair, and aortic valve replacement with findings of Fabry’s disease on surgical pathology. The case discussion focuses on the differential diagnosis for LVH and covers Fabry disease as an HCM mimic. Expert commentary was provided by Dr. Angelika Ewrin. The episode audio was edited by student Dr. Diane Masket. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media - An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic Pearls - An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic Left ventricular hypertrophy is a cardiac manifestation of several different systemic and cardiac processes, and its etiology should be clarified to avoid missed diagnosis and treatment opportunities. Fabry disease is a rare, X-linked inherited disease that can present cardiac and extra-cardiac manifestations, the former of which include hypertrophic cardiomyopathy, conduction defects, coronary artery disease, conduction abnormalities, arrhythmias, and heart failure.  The diagnosis of Fabry disease includes measurement of alpha-galactosidase enzyme activity as well as genetic testing to evaluate for pathogenic variants or variants of unknown significance in the GLA gene. Family members of patients diagnosed with Fabry disease should be screened based on the inheritance pattern.   Multimodality imaging can be helpful in the diagnosis of Fabry disease. Echocardiography can show left ventricular hypertrophy (LVH), reduced global strain, aortic and mitral valve thickening, and aortic root dilation with associated mild to moderate aortic regurgitation. Cardiac MRI can show hypertrophy of papillary muscles, mid-wall late gadolinium enhancement and low-native T1 signal.   The treatment of Fabry disease involves a multi-disciplinary approach with geneticists, nephrologists, cardiologists, nephrologists, and primary care doctors. Enzyme replacement therapy can delay the progression of cardiac disease.    Show Notes - An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic What are the causes of left ventricular hypertrophy? LVH is extremely common. It is present in 15-20% of the general population, and is more common in Black individuals, the elderly, obese or hypertensive individuals, with most cases being secondary to hypertension and aortic valve stenosis. In general terms, it is helpful to divide the causes of LVH into three main groups: high afterload states, obstruction to LV ejection, and intrinsic myocardial problems. Increased afterload states include both primary and secondary hypertension and renal artery stenosis. Mechanical obstruction includes aortic stenosis, subaortic stenosis, and coarctation of the aorta. Lastly, several intrinsic problems of the myocardium can cause LV hypertrophy, such as athletic heart with physiological LVH, hypertrophic cardiomyopathy with or without outflow obstruction, and infiltrative or storage diseases such as cardiac amyloidosis, Fabry’s disease, or Danon disease, among others.  How does Fabry disease present? Fabry disease is present in all races and is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene that result in reduced alpha-galactosidase enzyme activity,