sildenafil-citrate and Myocarditis

We report a 3-year-old boy weighing 13.5 kg who presented with intractable cardiac failure resulting from myocarditis and was treated by implantation of a HeartWare (HVAD) device. He was discharged home with the device. His cardiac function subsequently recovered, and the device was decommissioned. We believe this to be the youngest HVAD recipient and the only child to have recovered and had the device decommissioned.

Topics: Anticoagulants; Biopsy; Cardiomyopathy, Dilated; Child, Preschool; Combined Modality Therapy; Heart Failure; Heart-Assist Devices; Humans; Imaging, Three-Dimensional; Male; Milrinone; Myocarditis; Myocardium; Recovery of Function; Sildenafil Citrate; Thrombosis; Tomography, X-Ray Computed; Vasodilator Agents

Sildenafil inhibits cyclic GMP-specific phosphodiesterase type-5A (PDE5A) and can prevent cardiac hypertrophy and left ventricular (LV) dysfunction in mice subjected to severe pressure-overload. The pathophysiological role of sildenafil in adverse remodeling in the hypertensive heart after chronic renin-angiotensin aldosterone system stimulation is unknown. Therefore, we studied the efficacy of the PDE5A inhibitor sildenafil for treating advanced cardiac hypertrophy and LV remodeling due to angiotensin (Ang)II-induced heart failure (HF) in vivo. C57BL6/J mice were subjected to AngII-induced cardiac hypertrophy for 3 weeks and cardiac dysfunction, cardiac inflammatory stress response, adverse remodeling as well as apoptosis were documented. Mice were subsequently treated with sildenafil (100 mg/kg/day) or placebo with delay of 5 days for treating AngII infusion-induced adverse events. Compared to controls, AngII infusion resulted in impaired systolic (dP/dt (max) -46 %, SV -16 %, SW -43 %, E (a) +51 %, EF -37 %, CO -36 %; p < 0.05) and diastolic (dP/dt (min) -36 %, LV end diastolic pressure +73 %, Tau +21 %, stiffness constant β +74 %; p < 0.05) LV function. This was associated with a significant increase in cardiac hypertrophy and fibrosis. Increased inflammatory response was also indicated by an increase in immune cell infiltration and apoptosis. Treatment with sildenafil led to a significant improvement in systolic and diastolic LV performance. This effect was associated with less LV hypertrophy, remodeling, cardiac inflammation and apoptosis. PDE5A inhibition with sildenafil may provide a new treatment strategy for cardiac hypertrophy and adverse remodeling in the hypertensive heart.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Apoptosis; Cyclic GMP-Dependent Protein Kinase Type I; Cyclic Nucleotide Phosphodiesterases, Type 5; Cytokines; Extracellular Matrix; Heart Failure; Heart Function Tests; Hydralazine; Male; Mice; Mice, Inbred C57BL; Myocarditis; Myocardium; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Sildenafil Citrate; Sulfones; Vasoconstrictor Agents; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling