Pulmonary Vascular Response Patterns During Exercise in Left Ventricular Systolic Dysfunction Predict Exercise Capacity and Outcomes

Abstract

Background Elevated resting pulmonary arterial pressure (PAP) in patients with left ventricular systolic dysfunction (LVSD) purports a poor prognosis. However, PAP response patterns to exercise in LVSD and their relationship to functional capacity and outcomes have not been characterized. Methods and Results Sixty consecutive patients with LVSD (age 60±12 years, LV ejection fraction 0.31±0.07, mean±SD) and 19 controls underwent maximum incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. During low-level exercise (30 Watts), LVSD subjects compared to controls, had greater augmentation in mean PAPs (15±1 vs. 5±1 mmHg), transpulmonary gradients (5±1 vs. 1±1 mmHg), and effective PA elastance (0.05±0.02 vs. −0.03±0.01 mmHg/ml, p<0.0001 for all). A linear increment in PAP relative to work (0.28±0.12 mmHg/watt) was observed in 65% of LVSD patients, which exceeded that observed in controls (0.07±0.02 mmHg/watt, P<0.0001). Exercise capacity and survival was worse in patients with a PAP/watt slope above the median than in patients with a lower slope. In the remaining 35% of LVSD patients, exercise induced a steep initial increment in PAP (0.41±0.16 mmHg/watt) followed by a plateau. The plateau pattern, compared to a linear pattern, was associated with reduced peak VO2 (10.6±2.6 vs. 13.1±4.0 ml/kg/min, P=0.005), lower right ventricular stroke work index augmentation with exercise (5.7±3.8 vs. 9.7±5.0 g/m2, P=0.002), and increased mortality (HR 8.1, 95% CI 2.7-23.8, P<0.001). Conclusions A steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and survival in patients with LVSD, and may therefore represent therapeutic targets. Clinical Trial Information URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00309790)

Pulmonary Vascular Hemodynamic Response to Exercise in Cardiopulmonary Diseases

“…6,7 LAP increases during exercise with upstream transmission to mPAP. 5,6,[10][11][12] The increment in LAP during exercise also reduces pulmonary compliance and thereby leads to an increase in transpulmonary pressure gradient (mPAP minus LAP = TPG; Figure 3). 13 However, LAP exceeds the upper limit of resting normal in healthy young adult subjects only at very high cardiac outputs, in the range of 20 L/min and greater.…”

Exercise pulmonary haemodynamics: a test in search of purpose

“…Relying on TPR we cannot differentiate precapillary from post-capillary abnormalities. We have limited previous data to suggest that exercise elevation of pulmonary pressure in disease populations is associated with progression to PH [7,8] or worse outcomes [9][10][11]. The "disease" population consisted of those with standard risk factors for pulmonary arterial hypertension (PAH), those with chronic thromboembolic disease, those with Sickle cell disease and those with risk factors for left heart disease.…”

Clinical Significance of Exercise Pulmonary Hypertension in Secondary Mitral Regurgitation

“…12 Although prognostically robust, measurement of SPAP at peak exercise weakly reflects the dynamic and kinetic changes in pulmonary vascular resistance during exercise. Lewis et al, 13,14 using multipoint SPAP-flow plots, showed that patients with heart failure exhibiting a steeper slope or depicting a "plateau" pattern-a steep increase in SPAP at low workload followed by a flat slope at higher exercise load-had worse outcomes. However, this approach appears less feasible in daily routine practice than the straightforward measurement of SPAP at peak exercise.…”