Abstract 4379: Patients With Heart Failure and High Pulmonary Resistance Show Normal Transpulmonary BNP Uptake but Attenuation of cGMP Release, Responsive to Sildenafil
Introduction: Some, but not all patients with advanced heart failure (HF) develop precapillary pulmonary hypertension (PH) due to unidentified mechanisms. We hypothesized that diminished local sensitivity to endogenous BNP, reflected by low rate of cGMP release, might be responsible for PH.
Methods: 18 patients with systolic HF and high pulmonary vascular resistance (PVR > 3 w.u. in euvolemia, PHHF) and 28 HF patients with low PVR (non-PHHF) of similar age, gender, body size and HF severity (52±12 years, 54% ischemic, NYHA 2,9±0,7, EF 23±4%) underwent right heart cath. Samples were obtained from pulmonary artery (PA) catheter before and during wedging (02sat.>95%) to calculate transpulmonary BNP uptake and cGMP release (concentration difference × CO). PHHF patients were re-measured 1 hour after oral dose of sildenafil (40mg).
Results: PHHF had similar systemic resistance (SVR), BNPPA (684 vs. 607 pg/ml, p=0.8) as non-PHHF, but higher PVR (6.4 vs. 1.9 w.u., p <0.001), PA wedge pressure (26 vs 18 mmHg, p=0.001) and lower cardiac output (4,3 vs 3,6 l/min, p =0.01). Transpulmonary BNP uptake was similar (544 vs 230 ng/min, p=0.4), but cGMP release was significantly diminished in PHHF (Figure⇓). Sildenafil reduced PVR (−50%), SVR (−28%) and heart rate (−9%) and increased CO (23%) (all p<0.001), with parallel increase of pulmonary cGMP release (figure⇓), without affecting BNP uptake (p=0.5), norepinephrinePA or cAMPPA.
Conclusion: The study provides in vivo human evidence that diminished pulmonary cGMP production, rather than differences in BNP uptake, is critical for PH in HF. Sildenafil restores sensitivity of pulmonary vasculature to endogenous cGMP-dependent vasodilators.