Massive Coronary Microvascular Dysfunction in Severe Anderson-Fabry Disease Cardiomyopathy.

June 2019 1 Francesca Graziani, MD, PhD Rosa Lillo, MD Elena Panaioli, MD Gionata Spagnoletti, MD, PhD Isabella Bruno, MD Lucia Leccisotti, MD Riccardo Marano, MD Raffaele Manna, MD Filippo Crea, MD Anderson-Fabry disease (AFD) is a rare genetic lysosomal storage disorder caused by deficient activity of the enzyme α-galactosidase A, leading to progressive intracellular accumulation of neutral glycosphingolipids in different organs, including the heart. Left ventricular (LV) hypertrophy is the hallmark of cardiac involvement in AFD and represents one of the most important causes of morbidity and mortality in affected patients.1 Coronary microvascular dysfunction has a key role in AFD cardiomyopathy, accounting for the considerable prevalence of angina2 and may also represent the first sign of the disease in patients with no other sign of cardiac involvement.3 Indeed, coronary microvascular function is markedly impaired in AFD patients irrespective of LV hypertrophy and sex. Here, we report the case of a 49-year-old man with previous kidney transplant for progressive renal failure of unknown origin, referred to our Cardiology Unit for unexplained severe LV hypertrophy. The patient complained of angina and dyspnea for minimum effort. Genetic testing (mutation c.801+1G>T in GLA gene) and the low α-galactosidase A activity in peripheral blood lymphocytes confirmed the suspicion of AFD. The ECG showed sinus rhythm, short PR interval, LV hypertrophy with deep T wave inversion in the anterolateral leads (Figure 1A). The echocardiogram (Toshiba Artida Ultrasound system) showed significant biventricular hypertrophy (maximum LV wall thickness 26 mm, Figure 1B) with normal LV ejection fraction (biplane Simpson method 55%) but with severe reduction of global longitudinal strain (−4.6) and systolic tissue Doppler lateral and septal velocities (5.3 and 2.8 cm/s, respectively), with no regional wall-motion abnormalities. ECG-gated coronary computed tomography scan excluded significant epicardial coronary stenosis (Figure 2). We assessed myocardial blood flow at rest and after regadenoson infusion (400 μg) with 13N-labelled ammonia using positron emission tomography/ computed tomography. The patient had no significant perfusion defects at rest but developed a severe global subendocardial ischemia after pharmacological stress (Figure 3). Quantitative analysis of positron emission tomography images (Table 1) showed a severely reduced global and regional coronary flow reserve (normal values >2.5). Moreover, a transient severe LV systolic dysfunction was detected on Gated positron emission tomography images (LV ejection fraction from 48% at baseline to 30% at peak stress; Figure 4). In hypertrophic cardiomyopathy an abnormal response to pharmacological stress characterized by a transmural perfusion gradient leading to a significant drop in LV ejection fraction has been found in a high proportion of patients.4 To our knowledge, this is the first report of massive coronary microvascular dysfunction leading to transient LV systolic dysfunction as the likely cause of angina and dyspnea in a patient with a severe form of AFD cardiomyopathy. © 2019 American Heart Association, Inc. CARDIOVASCULAR IMAGES