Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension

Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to investigate the effects of maximum incremental exercise on the matching of RV contractility and afterload (i.e. right ventricular-pulmonary arterial [RV-PA] coupling) in patients with exercise PH (ePH) and pulmonary arterial hypertension (PAH). End-systolic elastance (Ees), pulmonary arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were determined using single-beat pressure-volume loop analysis in 40 patients that underwent maximum invasive cardiopulmonary exercise testing. Eleven patients had ePH, nine had PAH, and 20 were age-matched controls. During exercise, the impaired exertional contractile reserve in PAH was associated with blunted stroke volume index (SVI) augmentation and reduced peak oxygen consumption (peak VO2 %predicted). Compared to PAH, ePH demonstrated increased RV contractility in response to increasing RV afterload during exercise; however, this was insufficient and resulted in reduced peak RV-PA coupling. The dynamic RV-PA uncoupling in ePH was associated with similarly blunted SVI augmentation and peak VO2 as PAH. In conclusion, dynamic rest-to-peak exercise RV-PA uncoupling during maximum exercise blunts SV increase and reduces exercise capacity in exercise PH and PAH. In ePH, the insufficient increase in RV contractility to compensate for increasing RV afterload during maximum exercise leads to deterioration of RV-PA coupling. These data provide evidence that even in the early stages of PH, RV function is compromised.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Pulmonary Vascular Resistance During Exercise Predicts Long-Term Outcomes in Heart Failure With Preserved Ejection Fraction

Background: In heart failure with preserved ejection fraction (HFpEF), the prognostic value of pulmonary vascular dysfunction (PV-dysfunction), identified by elevated pulmonary vascular resistance (PVR) at peak exercise, is not completely understood. We evaluated the long-term prognostic implications of PV-dysfunction in HFpEF during exercise in consecutive patients undergoing invasive cardiopulmonary exercise testing for unexplained dyspnea. Methods: Patients with HFpEF were classified into 2 main groups: resting HFpEF (n = 104, 62% female, age 61 years) with a pulmonary arterial wedge pressure (PAWP) >15 mmHg at restand exercise HFpEF (eHFpEFn = 81) with a PAWP 20 mmHg during exercise. The eHFpEF group was further subdivided into eHFpEF + PV-dysfunction (peak PVR 80 dynes/s/cm(-5)n = 55, 60% female, age 64) group and eHFpEF PV-dysfunction (peak PVR = 80 dynes/s/cm(-5) was a predictor of HF-related hospitalization for eHFpEF (hazard ratio 5.73, 95% confidence interval 1.05-31.22, P = .01). In conclusion, the present study provides insight into the impact of PV-dysfunction on outcomes of patients with exercise-induced HFpEF. An elevated peak PVR is associated with a high risk of HF-related hospitalization.National Natural Science Foundation of ChinaNatural Science Foundation of ChongqingSao Paulo Research Foundation (FAPESP)Brazilian National Council for Scientific and Technological Development (CNPq)National Institutes of Health (NIH)Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 1, Chongqing, Peoples R ChinaBrigham & Womens Hosp, Pulm & Crit Care Med, Ctr Pulm Heart Dis, 75 Francis St, Boston, MA 02115 USAFed Univ Sao Paulo UNIFESP, Div Resp Dis, Dept Med, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Div Resp Dis, Dept Med, Sao Paulo, BrazilNNSFC: 81170188NNSFC: 30971212CSCT: 2009BB5069FAPESP: 2014/12212-5CNPq: 232643/2014-8NIH: U01HL125215Web of Scienc

Pulmonary haemodynamics during recovery from maximum incremental cycling exercise

Assessment of cardiac function during exercise can be technically demanding, making the recovery period a potentially attractive diagnostic window. However, the validity of this approach for exercise pulmonary haemodynamics has not been validated. The present study, therefore, evaluated directly measured pulmonary haemodynamics during 2-min recovery after maximum invasive cardiopulmonary exercise testing in patients evaluated for unexplained exertional intolerance. Based on peak exercise criteria, patients with exercise pulmonary hypertension (ePHn=36), exercise pulmonary venous hypertension (ePVHn=28) and age-matched controls (n=31) were analysed. By 2-min recovery, 83% (n=30) of ePH patients had a mean pulmonary artery pressure (mPAP) < 30 mmHg and 96% (n=27) of ePVH patients had a pulmonary arterial wedge pressure (PAWP) < 20 mmHg. Sensitivity of pulmonary hypertension-related haemodynamic measurements during recovery for ePH and ePVH diagnosis was <= 25%. In ePVH, pulmonary vascular compliance (PVC) returned to its resting value by 1-min recovery, while in ePH, elevated pulmonary vascular resistance (PVR) and decreased PVC persisted throughout recovery. In conclusion, we observed that mPAP and PAWP decay quickly during recovery in ePH and ePVH, compromising the sensitivity of recovery haemodynamic measurements in diagnosing pulmonary hypertension. ePH and ePVH had different PVR and PVC recovery patterns, suggesting differences in the underlying pulmonary hypertension pathophysiology.Sao Paulo Research Foundation (FAPESP)Brazilian National Council for Scientific and Technological Development (CNPq)Austrian Science Fund (FWF), Erwin SchroedingerNIHBrigham & Womens Hosp, Dept Med, Pulm & Crit Care Med, Clin 3,75 Francis St, Boston, MA 02115 USAHarvard Med Sch, Boston, MA USABrigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USAFed Univ Sao Paulo UNIFESP, Dept Med, Div Resp Dis, Sao Paulo, BrazilMed Univ Vienna, Dept Internal Med 2, Div Cardiol, Vienna, AustriaFed Univ Sao Paulo UNIFESP, Dept Med, Div Resp Dis, Sao Paulo, BrazilFAPESP: 2014/12212-5CNPq: 232643/2014-8Austrian Science Fund (FWF), Erwin Schroedinger: J3522-B13NIH: 2R01HL060234-12A1NIH: U01HL125215-01Web of Scienc

Impaired systemic oxygen extraction in treated exercise pulmonary hypertension: a new engine in an old car?

Ambrisentan in 22 patients with pulmonary hypertension diagnosed during exercise (ePH) improved pulmonary hemodynamics; however, there was only a trend toward increased maximum oxygen uptake (VO2max) secondary to decreased maximum exercise systemic oxygen extraction (Ca-vO2). We speculate that improved pulmonary hemodynamics at maximum exercise “unmasked” a pre-existing skeletal muscle abnormality

Functional impact of exercise pulmonary hypertension in patients with borderline resting pulmonary arterial pressure

Borderline resting mean pulmonary arterial pressure (mPAP) is associated with adverse outcomes and affects the exercise pulmonary vascular response. However, the pathophysiological mechanisms underlying exertional intolerance in borderline mPAP remain incompletely characterized. In the current study, we sought to evaluate the prevalence and functional impact of exercise pulmonary hypertension (ePH) across a spectrum of resting mPAP’s in consecutive patients with contemporary resting right heart catheterization (RHC) and invasive cardiopulmonary exercise testing. Patients with resting mPAP 0.05) and similar underlying mechanisms of exercise intolerance compared with non-PH (peak oxygen delivery 1868 ± 599 mL/min versus 1756 ± 720 mL/min versus 2482 ± 875 mL/min, respectively; P < 0.05), associated with chronotropic incompetence, increased right ventricular afterload and signs of right ventricular/pulmonary vascular uncoupling. In conclusion, ePH is most frequently found in borderline mPAP, reducing exercise capacity in a manner similar to rPH. When borderline mPAP is identified at RHC, evaluation of the pulmonary circulation under the stress of exercise is warranted