P68 dilated cardiomyopathy and microdeletion syndrome: a case report

Abstract A 45–year–old man was admitted to our Coronary Care Unit because of acute pulmonary edema and atrial flutter with high ventricular response. The patient was an active smoker, obese and reported a previous alcohol abuse. Blood tests showed increased NT–proBNP values. Transthoracic echocardiography showed a severely enlarged and dysfunctional left ventricle (LVEF 15%). Acute phase treatment required noninvasive ventilation, amine support, and electrical cardioversion with progressive improvement of patient’s clinical condition. At coronary angiography no significant coronary stenosis was found. (fig.2). Cardiac magnetic resonance showed no area of fibrosis or inflammation(fig.3). Furthermore, a new diagnosis of diabetes mellitus type 2 and mild cognitive impairment was also made during hospitalization. Upon clinical stabilization, therapy with bisoprolol, sacubitril/valsartan, spironolactone, furosemide, and direct anticoagulant was introduced and titrated with progressive improvement until normalization during follow–up of systolic function indices, ventricular volumes, and nt–proBNP values until normalization at approximately 6 months after discharge. Cardiopulmonary exercise test was performed and found good cardiopulmonary performance and absence of cardiogenic limitation to exercise (VO2 peak 22.9 ml/min/kg corresponding to 93% of predicted and VO/HR 18 ml/beat, VE/VCO2 slope equal to 24). Genetic test showed a missense mutation in heterozygosity of LMNA gene (1634 G>A, p. Arg545His) currently coded as likely pathogenic and heterozygous deletion of 534 kb at the level of the short arm (p) of chromosome 16 at band p11.2. Dilated cardiomyopathies associated with mutations in the LMNA gene, coding for Lamina A/C (a component of the cellular basal lamina), tend to have an inauspicious prognosis as they are related to arrhythmic and extracardiac manifestations (myopathies, lipodystrophies, and neuropathies). 16p11 microdeletion syndrome is characterized by obesity and cognitive impairment, frequently associated with congenital heart disease, less often with dilated and hypertrophic cardiomyopathy pictures. The rapid introduction and titration to the maximum tolerated dose of heart failure therapy had an extremely positive effect in our patient who had an overlapping of genetically determined dilated cardiomyopathy and 16p11 microdeletion syndrome.