SESSION TITLE: Pulmonary Hypertension
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 28, 2013 at 01:45 PM - 03:15 PM
PURPOSE: Previous investigators have reported that < 10% of patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) are vasoreactive and respond favorably to extended treatment with calcium channel blockers (Sitbon, 2005). The molecular basis of this vasoreactive phenotype remains unknown. The purpose of the present study was to search for mutations in a gene which codes for acid sensitive potassium channel proteins among IPAH patients who demonstrated acute vasoreactivity and a sustained response to treatment with calcium channel blockers.
METHODS: We identified 10 IPAH patients who demonstrated acute vasoreactivity (mean PA pressure decreased at least 10 mmHg to < 41 mmHg) when they underwent diagnostic pulmonary artery catheterization at 1 of 7 different institutions in the United States. All 10 were treated with calcium channel blockers and demonstrated a sustained clinical response confirmed by repeat pulmonary artery catheterization. DNA samples extracted from whole blood were tested for mutations in the coding regions of KCNK3 with 4 primer sets. PCR was performed with universal M13 sequencing primers and 1 ul of big dye. Analysis was done on an ABI 3730 instrument.
RESULTS: The patients included 9 women and 1 man. Seven of 10 patients described functional class II symptoms at the time of diagnosis, and none had another family member affected by IPAH. Baseline characteristics (mean ± SD) included: age 49.7 ± 10.1 years; mean pulmonary artery pressure = 48.0 ± 10.7 mmHg; pulmonary artery occlusion pressure = 7.1 ± 4.1; right atrial pressure = 4.8 ± 3.0 mmHg; pulmonary vascular resistance = 8.7 ± 3.7 Wood units, and cardiac index = 2.8 ± 2.8 l/min/m2. All 10 patients had a sustained response to calcium channel blockers documented by repeat pulmonary artery catheterizations (range 2 to 21 years on treatment). We did not identify sequence variations of KCNK3 in these 10 vasoreactive IPAH patients.
CONCLUSIONS: KCNK3 mutations were not identified in this cohort of vasoreactive IPAH patients. The molecular basis of vasoreactive IPAH remains uncertain.
CLINICAL IMPLICATIONS: Identifcation of molecular markers to guide treatment of pulmonary arterial hypertension may become important.
DISCLOSURE: The following authors have nothing to disclose: Ikue Nakayama, Hunter Best, Lynn Brown, Wendy Chung, C. Gregory Elliott
This presentation involves the research application of genetic testing to a subgroup of patients with pulmonary hypertension.