Background/Purpose: Pulmonary hypertension (PH), defined as a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg on right heart catheterization (RHC), is a leading cause of death in patients with systemic sclerosis (SSc).  Although RHC is the gold standard for diagnosing PH, it is an expensive, invasive test with significant associated risks.  Transthoracic echocardiogram (TTE) and pulmonary function testing (PFT) are standard noninvasive screening methods used to assess SSc patients for PH.  However, both are limited in their ability to distinguish between SSc patients with and without PH.  The existence of an accurate, noninvasive technique to screen for PH in the SSc population is an important unmet need.

The submaximal heart and pulmonary evaluation (SHAPE) is a noninvasive, submaximal stress test that consists of a 5.5 inch high step that patients step up and down on for 3 minutes.  During the test, end tidal carbon dioxide, which is equivalent to the ratio of cardiac output to pulmonary blood flow and reflects the severity of PH, is monitored.  Our aim was to assess the correlation between change in end tidal carbon dioxide (ΔP_ETCO2) from rest to end-exercise on the SHAPE test and mPAP on RHC.  We hypothesized that ΔP_ETCO2 would be strongly negatively correlated with mPAP.

Methods: This is a retrospective cohort study of patients with limited cutaneous (lc) or diffuse cutaneous (dc) SSc who underwent a SHAPE test and RHC between November 2008 and May 2012.  Charts of 679 patients in an academic cardiology practice were reviewed; 70 patients had a diagnosis of SSc, 19 of whom had undergone both a SHAPE test and RHC and were included in this study.  The primary outcome was correlation between ΔP_ETCO2 and mPAP.  Statistical analysis was performed using Spearman’s correlation and multivariable linear regression.

Results: The mean age of subjects was 61 years (± 12.5); 84% were female, 84% had lcSSc, and 79% had PH.  ΔP_ETCO2 was significantly negatively correlated with mPAP (r = -0.82, p < 0.0001) (see Table).   In a multivariable linear regression model evaluating the relationship between ΔP_ETCO2 and mPAP, and controlling for age, sex, time between SHAPE and RHC, and change in medications between SHAPE and RHC, ΔP_ETCO2remained significantly associated with mPAP (β = -1.91, p < 0.001).  The SHAPE had better sensitivity, specificity, positive predictive value, and negative predictive value for PH than did TTE or PFTs.

 

Performance Characteristics and Correlation of SHAPE, TTE, and PFTs with RHC (N=19)
Test*	Sensitivity**	Specificity**	Positive Predictive Value (PPV)**	Negative Predictive Value (NPV)**	Spearman’s Correlation†	P-value for Spearman’s Correlation
SHAPE (ΔPETCO2 < 4 mmHg)	100%	75%	93.8%	100%	-0.82	0.0001
TTE (systolic pulmonary artery pressure [sPAP] > 35 mmHg )	80%	25%	80%	25%	0.74	0.0004
PFTs (forced vital capacity/diffusion capacity [FVC/DLCO] >  1.6)††	91.7%	75%	91.7%	75%	0.53	0.034
* Cut-points were derived from the literature ** Using RHC as the gold standard for diagnosis of PH (mPAP ≥ 25 mmHg) † Correlation is with mPAP on RHC †† 16 of the 19 patients had PFTs with DLCO

Conclusion: ΔP_ETCO2 as measured by the SHAPE has a very strong, statistically significant negative correlation with mPAP on RHC, and is better correlated with mPAP than are sPAP on TTE or FVC/DLCO.  The SHAPE has excellent sensitivity, specificity, PPV, and NPV in this small group of SSc patients with a high prevalence of PH.  The SHAPE may be a better screening test for PH in patients with SSc than TTE or PFTs.  Larger prospective studies investigating the ability of the SHAPE to distinguish between SSc patients with and without PH are needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-submaximal-heart-and-pulmonary-evaluation-a-novel-noninvasive-test-to-identify-pulmonary-hypertension-in-patients-with-systemic-sclerosis/