Secondary pulmonary hypertension (PH) is an important prognostic indicator in patients with systolic heart failure (HF), but the pattern of increase in pulmonary arterial pressure (PAP) during exercise and its relationship to exercise capacity and pulmonary capillary wedge pressure (PCWP) have not been comprehensively investigated. We hypothesized that HF patients would develop an increase in PAP out of proportion to the increase in PCWP during exercise and that the rate of PAP increase during exercise would predict exercise capacity in HF. Thirty-three patients with systolic HF (mean±SD, age 58 ± 7 years, left ventricular ejection fraction 0.27 ± 0.05, peak oxygen uptake 11.2 ± 3.2 ml/kg/min) and 10 normal subjects (age 53±9, sex, VO2) underwent cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. There was a linear relationship between PAP and work rate in watts (R>0.85 for all subjects) whereas no consistent relationship between PCWP and work rate was present (R=0.02– 0.93). HF patients had a 3-fold greater rate of increase in PAP per watt than normals (slope=0.23±0.02 vs. 0.07±0.002 mmHg/W respectively, p<0.0001). In HF patients, PAP increased out of proportion to PCWP, as indicated by the slope of the gradient between PAP and PCWP (0.11±0.005 mmHg/W in HF vs. 0.01±0.005 mmHg/W in normals, p<0.0001). In HF patients, PAP slope, but not PCWP slope, inversely correlated with exercise capacity as measured by peak VO
2
(R=−0.41, p=0.04 and R=−0.12, p=0.56, respectively). Fifteen of the HF subjects underwent repeated exercise testing after 12-weeks of treatment with the pulmonary vasodilator sildenafil, with a resultant decrease in slope of the PAP-PCWP gradient from 0.11±0.02 to 0.07±0.01 mmHg, P<0.05. In patients with systolic HF there is a linear increase in PAP/watt that is out of proportion to the increase in PCWP/watt and inversely correlated with exercise capacity. Abnormal pulmonary vasoconstriction in response to physical activity in HF may represent a target for therapeutic intervention in HF.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
Can Transthoracic Doppler Echocardiography Predict the Discrepancy Between Left Ventricular End-Diastolic Pressure and Mean Pulmonary Capillary Wedge Pressure in Patients With Heart Failure?