sildenafil-citrate and Cardiomyopathy--Hypertrophic

Mutations in the TMEM70 are the most common cause of nuclear ATP synthase deficiency resulting in a distinctive phenotype characterized by severe neonatal hypotonia, hypertrophic cardiomyopathy (HCMP), facial dysmorphism, severe lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria (3-MGA).. We collected 9 patients with genetically confirmed TMEM70 defect from 8 different families. Six were homozygous for the c.317-2A>G mutation, 2 were compound heterozygous for mutations c.317-2A>G and c.628A>C and 1 was homozygous for the novel c.701A>C mutation. Generalized hypotonia, lactic acidosis, hyperammonemia and 3-MGA were present in all since birth. Five patients presented acute respiratory distress at birth requiring intubation and ventilatory support. HCMP was detected in 5 newborns and appeared a few months later in 3 additional children. Five patients showed a severe and persistent neonatal pulmonary hypertension (PPHN) requiring Nitric Oxide (NO) and/or sildenafil administration combined in 2 cases with high-frequency oscillatory (HFO) ventilation. In 3 of these patients, echocardiography detected signs of HCMP at birth.. PPHN is a life-threatening poorly understood condition with bad prognosis if untreated. Pulmonary hypertension has rarely been reported in mitochondrial disorders and, so far, it has been described in association with TMEM70 deficiency only in one patient. This report further expands the clinical and genetic spectrum of the syndrome indicating PPHN as a frequent and life-threatening complication regardless of the type of mutation. Moreover, in these children PPHN appears even in the absence of an overt cardiomyopathy, thus representing an early sign and a clue for diagnosis.

Topics: Cardiomyopathy, Hypertrophic; Child, Preschool; Female; Humans; Hyperammonemia; Hypertension, Pulmonary; Infant; Infant, Newborn; Male; Membrane Proteins; Mitochondrial Diseases; Mitochondrial Proteins; Mutation; Nitric Oxide; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Cardiomyopathy, Hypertrophic; Female; Heart Transplantation; Humans; Hypertension; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

This case report describes a patient with hypertrophic cardiomyopathy who developed symptomatic atrial fibrillation on two occasions after ingesting sildenafil citrate (Viagra). Sildenafil citrate should be withheld or used with extreme caution in persons with hypertrophic obstructive cardiomyopathy.

Topics: Acute Disease; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Cardiomyopathy, Hypertrophic; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Stroke Volume; Sulfones; Tachycardia, Ventricular; Ventricular Outflow Obstruction; Ventricular Premature Complexes