Prospective Assessment of Pulmonary Hypertension in Children with Chuvash Polycythemia.

Background: Chuvash Polycythemia (CP) is an autosomal recessive disorder that is endemic to the Chuvash region of Russia; however, it does occur worldwide. It is characterized by a mutation (598C>T) of the von Hippel Lindau gene, a negative regulator of hypoxia-sensing, and increased levels of hypoxia inducible factor-alpha during normoxia. CP is manifested by vertebral hemangiomas, varicose veins, hypotension, elevated concentrations of products of hypoxia-induced genes (serum vascular endothelial growth factor and endothelin-1), and premature mortality related to cerebral vascular events and peripheral thrombosis. Echocardiography (echo) studies in adults with CP suggest an increased prevalence of pulmonary hypertension (PH), but these findings have not been validated in children with CP.

Methods: This work is supported by an NIH grant evaluating the prevalence, outcomes, pathophysiology, vascular response, and gene polymorphisms of PH in sickle cell disease and CP. We traveled to Cheboksary, Russia to prospectively enroll children with CP and age and gender matched controls to undergo echo for assessment of left ventricular (LV) systolic and diastolic function, LV size and mass, estimated right ventricular (RV) systolic pressure by tricuspid regurgitation velocity (TRV), and the RV to systemic systolic blood pressure (SBP) ratio. Data was compared between CP and control children.

Results: 24 CP and 11 control patients were enrolled in the study. 20 CP and 9 control patients had measurable TRV. 4 of 20 CP and none of the control patients had TRV > 2.5 m/sec (max TRV 2.89 m/sec). There was a trend towards higher TRV and estimated RV pressure in CP patients. Systolic function, LV size, and mass were the same in both groups. Diastolic function was normal in both groups but significantly better in CP patients. SBP was the same in both groups. Systemic mean and diastolic BP, adjusted for age, was significantly lower in CP children.

Conclusions: Preliminary prospective data show a trend towards higher echo derived estimates of RV pressure in children with CP that can not be explained by hypertension or diastolic dysfunction. Rather, congenital upregulation of the hypoxic response may be responsible. Continued patient recruitment and correlation of TRV with other variables will allow for a better understanding of PH in children with CP.