Pulmonary Hemodynamics During Exercise

    Riel, A.C.J.M. van | AMC Amsterdam | 23 augustus 2016 |

Pulmonary hypertension is a well-known complication of many underlying diseases and associated with increased mortality, morbidity and cardiac events(1). By stressing the pulmonary circulation in patients with normal resting hemodynamics, i.e. by using exercise, an abnormal pulmonary vascular response can be detected, which harbours important clinical implications.(2) This abnormal pulmonary vascular response might represent a pre-clinical phase of pulmonary arterial hypertension(3), but can also be present in patients with left-sided valvular heart disease(4) or heart failure with preserved ejection fraction(5). In all these patients, early detection of this progressive disease allows for adequate and timely treatment, with a chance of better outcomes(6).
During the 2016 American College of Cardiology annual conference we were allowed to present our results on pulmonary hemodynamics during exercise. First, we presented the performance of exercise echocardiography as a non-invasive screening tool on a flat board poster. Second, we presented a novel finding of dynamic right ventricular outflow tract obstruction during exercise, which has direct clinical implications for the accuracy of exercise echocardiography to assess pulmonary pressures, as an oral presentation.

Poster presentation

Exercise echocardiography is technically challenging and limited data exist regarding the accuracy of echocardiography to estimate pulmonary arterial pressure (PAP) during exercise. Therefore we aimed to determine the accuracy of echocardiography during exercise by simultaneous comparison with invasive pressure measurements. We included a total of 65 patients with exertional intolerance undergoing upright invasive exercise testing with simultaneous echocardiography. We compared tricuspid regurgitation (TR) Doppler estimates of PAP at rest and peak exercise with invasively measured PAP . TR Doppler envelopes were assessed for quality using two predefined criteria (1) extension of the signal for at least half of systole, and (2) well defined border. Envelopes were graded as quality A if all criteria were applicable, quality B if one criterion was missing and quality C if both criteria were missing. Correlation, Bland-Altman and receiver-operating characteristic analyses were performed to evaluate agreement and diagnostic accuracy.
Mean age was 62±13 years and 31% were male. High quality (grade A) TR Doppler was present in 68% at rest, 34% at peak exercise, and 28% for both. For grade A TR signals, non-invasive measures of systolic PAP correlated reasonably well with invasive measurement at rest (r=0.72 ,p<0.001; bias=-2.9±8.0 mmHg) and peak exercise (r=0.75, p<0.001; bias=-1.9±15.6), as did the change in systolic PAP (r=0.70, p<0.001; bias 0.0±11.0). Lower quality (grade B and C) TR signals correlated poorly overall with invasive measurements. Mean PAP-to-workload ratio, at a threshold of 1.4 mmHg/10W, was able to identify abnormal pulmonary hemodynamic response during exercise (>2.5 mmHg/L/min increase) in patients with high quality TR signals, with 91% sensitivity and 82% specificity (AUC 0.90 [95% CI 0.77–1.0], p=0.001).
Agreement between echocardiographic and invasive measures of pulmonary pressures during upright exercise is good among the subset of patients with high quality TR Doppler signal. While the limits of agreement are broad, our results suggest that sensitivity is adequate to screen for abnormal pulmonary hemodynamic response during exercise if high quality TR signal can be obtained.

Oral presentation

When using echocardiography to estimate pulmonary arterial (PA) pressure at rest and with exercise, one must account for fixed right ventricular outflow tract (RVOT) obstruction. Dynamic RVOT obstruction during exercise could similarly confound accurate non-invasive estimation of PA pressure. Therefore we studied a retrospective cohort of patients with unexplained exertional intolerance referred for invasive upright cycle cardiopulmonary exercise testing. We excluded patients with supine resting RVOT gradient >10mmHg. RVOT gradient was calculated upright at rest and at peak exercise from simultaneously transduced right ventricular and pulmonary artery pressures. Abnormal pulmonary vascular response was defined as mean pulmonary arterial pressure (mPAP) >30mmHg at peak exercise.
A total of 294 patients were included (age 59.7±15.5y, 49.0% male). Upright resting and peak RVOT gradients averaged 8.8±5.5 and 18.6±11.4 mmHg, respectively. The gradient was ≥33mmHg in 11.2% of patients. Such striking RVOT gradients did not seem to correspond to clinical or hemodynamic findings suggestive of right heart failure; higher peak RVOT gradient was associated with younger age (β=-0.45 mmHg/year, p<0.001), higher peak cardiac index (β=+0.53 mmHg/l/min/m2, p<0.001) and higher peak VO2 (β=0.58 mmHg per mL/kg/min, p<0.001). Among n=147 with normal pulmonary hemodynamics with exercise (peak mPAP ≤30mmHg), only 1.4% had invasively measured systolic PAP >50mmHg, while RV systolic pressure was >50mmHg in 75%, >60mmHg in 37%, and >70mmHg in 15.6% of these patients with normal exercise mPAP.
A substantial proportion of patients with normal PA pressure response to exercise have elevated RV systolic pressure because of a gradient across the RVOT presumably due to dynamic physiologic obstruction. This phenomenon inherently limits the ability of echocardiography to identify abnormal pulmonary vascular response during upright exercise.

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6. Simonneau G, Galiè N, Jansa P, Meyer GMB, Al-Hiti H, Kusic-Pajic A, et al. Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients. Int J Cardiol. 2014 Mar 15;172(2):332–9.

Keyword: Pulmonary hypertension echocardiography exertional intolerance

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