Stress Doppler echocardiography for early detection of systemic sclerosis-associated pulmonary arterial hypertension

Christian Nagel, Philipp Henn, Nicola Ehlken, Antonello D'Andrea, Norbert Blank, Eduardo Bossone, Anke Böttger, Christoph Fiehn, Christine Fischer, Hanns-Martin Lorenz, Frank Stöckl, Ekkehard Grünig, Benjamin Egenlauf, Christian Nagel, Philipp Henn, Nicola Ehlken, Antonello D'Andrea, Norbert Blank, Eduardo Bossone, Anke Böttger, Christoph Fiehn, Christine Fischer, Hanns-Martin Lorenz, Frank Stöckl, Ekkehard Grünig, Benjamin Egenlauf

Abstract

Introduction: In patients with systemic sclerosis (SSc), associated pulmonary arterial hypertension (SSc-APAH) is the leading cause of death. The objective of this prospective screening study was to analyse sensitivity and specificity of stress Doppler echocardiography (SDE) in detecting pulmonary hypertension (PH).

Methods: Pulmonary artery pressures and further parameters of PH were assessed by echocardiography and right heart catheterisation (RHC) at rest and during exercise in patients with SSc. Investigators of RHC were blinded to the results of non-invasive measurements.

Results: Of 76 patients with SSc (64 were female and mean age was 58±14 years), 22 (29 %) had manifest PH confirmed by RHC: four had concomitant left heart diseases, three had lung diseases, and 15 had SSc-APAH. Echocardiography at rest missed PH diagnosis in five of 22 patients with PH when a cutoff value for systolic pulmonary arterial pressure (PASP) was more than 40 mm Hg at rest. The sensitivity of echocardiography at rest was 72.7 % (95 % confidence interval (CI) 0.52-0.88), and specificity was 88.2 % (95 % CI 0.78-0.95). When a cutoff value for PASP was more than 45 mm Hg during low-dose exercise, SDE missed PH diagnosis in one of the 22 patients with PH and improved sensitivity to 95.2 % (95 % CI 0.81-1.0) but reduced specificity to 84.9 % (95 % CI 0.74-0.93). Reduction of specificity was partly due to concomitant left heart disease.

Conclusions: The results of this prospective cross-sectional study using RHC as gold standard in all patients showed that SDE markedly improved sensitivity in detecting manifest PH to 95.2 % compared with 72.7 % using echocardiography at rest only. Thus, for PH screening in patients with SSc, echocardiography should be performed at rest and during exercise.

Trial registration: ClinicalTrials.gov NCT01387035. Registered 29 June 2011.

Figures

Fig. 1
Fig. 1
Results of the screening of 76 patients with systemic sclerosis (SSc) by right heart catheterisation (RHC). This figure shows that within the screening assessment 29 % of the 76 patients were newly diagnosed with a manifest pulmonary hypertension (PH) and 43 % had no signs of PH. CHD coronary heart disease, HFpEF heart failure with preserved ejection fraction, mPAP mean pulmonary arterial pressure, PH-ILD pulmonary hypertension-interstitial lung disease
Fig. 2
Fig. 2
a Correlation of systolic pulmonary arterial pressures (PASP) determined by echocardiography and mean pulmonary arterial pressure (mPAP) at rest. The x-axis shows the PASP values measured by echocardiography at rest, the y-axis the values measured by right heart catheterisation (RHC). The values of each patient are given in red, indicating that the assessment including RHC diagnosed a manifest pulmonary hypertension (PH) with an mPAP at rest of at least 25 mm Hg. The symbols in green are the values of systemic sclerosis patients with no manifest PH at rest. As cutoff value for the PASP, 40 mm Hg at rest was used. The sensitivity was 72.7 % (95 % confidence interval (CI) 52–88 %) and the specificity was 88.2 % (95 % CI 78–95 %) in diagnosing a PH (P < 0.001). There was a positive correlation (r = 0.860) between PASP and mPAP. b Correlation of PASP at 25 Watts and mPAP at rest. The x-axis shows the PASP values measured by echocardiography during low-dose exercise at 25 Watts. The y-axis shows the values measured by RHC at rest. Sensitivity was 95.2 % (95 % CI 81–100 %) and specificity was 84.9 % (95 % CI 74–93 %) in diagnosing a PH using a cutoff PASP value of 45 mm Hg at 25 Watts (P < 0.001). Positive correlation (r = 0.860) between PASP at 25 Watts and mPAP
Fig. 3
Fig. 3
Receiver operating characteristic (ROC) curves of sensitivity and specificity of systolic pulmonary arterial pressures (PASP) at rest and at 25 Watts. The threshold for detection of pulmonary hypertension was set at 40 mm Hg for echocardiography at rest and at 45 mm Hg for echocardiography during exercise. All possible thresholds were analysed by ROC analysis for their suitability. The cutoff value for echocardiography during exercise at 45 mm Hg revealed the highest combination of sensitivity and specificity. For the examination at rest, a decrease of the cutoff value would have led to an increase of sensitivity but a crucial decrease of specificity. AUC area under the curve, CI confidence interval
Fig. 4
Fig. 4
Correlation of systolic pulmonary arterial pressure (PASP) at 25 Watts and PASP at rest. Cutoff values are 45 mm Hg for PASP at 25 Watts and 40 mm Hg PASP at rest. Circles represent patients without pulmonary hypertension (PH) verified by right heart catheterisation (RHC); squares are patients with manifest associated pulmonary arterial hypertension according to RHC as gold standard. PASP at rest with a cutoff value of 40 mm Hg would have missed five manifest PH patients; PASP at 25 watts with a cutoff value of 45 mm Hg would have missed only one patient with a slightly lower specificity. CI confidence interval

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