Reduced Right Ventricular Output Reserve Observed in SSc With Elevated PAP

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Researchers observed that patients with mildly elevated mPAP at rest had lower right ventricular output reserve and PAC during exercise than patients with normal mPAP at rest.
Researchers observed that patients with mildly elevated mPAP at rest had lower right ventricular output reserve and PAC during exercise than patients with normal mPAP at rest.

Patients with systemic sclerosis (SSc) with mildly elevated resting mean pulmonary artery pressure (PAP) appear to have reduced right ventricular (RV) output reserve and pulmonary arterial compliance (PAC) compared with patients with normal resting mPAP, according to findings published in Arthritis & Rheumatology.

Pulmonary arterial hypertension (PAH) is a frequent complication of SSc, but the pathophysiology involved in exercise intolerance in mild PAH remains uncertain. Investigators sought to better characterize these mechanisms and compare RV output reserve and PAC among 3 groups of patients with different levels of PAH, with the goal of improving early detection of pulmonary vascular disease.

Between 2012 and 2016, a total of 112 patients with SSc (mean age, 57±13 years; 78.6% women) referred to a single center for pulmonary hypertension screening were enrolled in a prospective study (ClinicalTrials.gov identifier: NCT01387035). Participants underwent right heart catheterization and were divided into 3 groups according to resting mPAP: normal (≤20 mm Hg), mildly elevated (21-24 mm Hg) and frank pulmonary hypertension (≥25 mm Hg). There were 72, 14, and 26 participants in each study group.

Groups were evaluated by right heart catheterization at rest and during exercise and values were compared in terms of cardiac index, cardiac output, 6-minute walking distance, pulmonary vascular resistance (PVR), and PAC. Together, these metrics were used to assess RV and pulmonary vascular responses to exercise. Pearson correlation analyses were used to examine possible associations between at-rest PAC and 6-minute walking distance and changes in cardiac index and cardiac output.

The 3 groups registered significantly different mean 6-minute walking distance (P <.0001). Those with normal resting mPAP walked the farthest, followed by patients with mild mPAP elevation, and those with frank pulmonary hypertension posted the lowest distances. Exercise capacity, as measured by peak workload, was similarly ordered, with individuals with mildly elevated mPAP falling between the normal (highest workload) and frank pulmonary hypertension (lowest workload) groups. At rest, significantly higher PVR was seen in patients with mildly elevated mPAP compared with normal mPAP (P =.001).

Compared with patients with normal mean PAP, patients with mild elevation displayed significantly reduced 6 minute walking distance (P <.008), decreased change in cardiac index (P =.006), decreased cardiac output (P =.003), and increased PVR (P =.0002) during exercise. In addition, individuals with mildly elevated mPAP also demonstrated lower PAC than individuals with normal mPAP, both at rest (P =.016) and during exercise at 25 watts (P =.033) and 75 watts (P =.024). Significant correlations were found between at-rest PAC and 6-minute walking distance (P <.001) and change in cardiac output (P =.018), and a correlative trend was found between PAC and change in cardiac index (P =.064).

Collectively, these results indicate that patients with mildly elevated mPAP at rest have lower RV output reserve and PAC during exercise than patients with normal mPAP at rest.

Study limitations include small sample size, capping of reported workloads at 75 watts, possible overestimation of PAC, and lack of 2-dimensional echocardiographic exercise imaging.

The authors noted that, “These findings give further evidence for mildly elevated mPAP reflecting an early stage of pulmonary vascular disease and RV dysfunction.” They add that future research should evaluate the use of targeted PAH medication for persons with mild mPAP elevation.

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Reference

Nagel C, Marra AM, Benjamin N, et al. Reduced right ventricular output reserve in patients with systemic sclerosis and mildly elevated pulmonary arterial pressures [published online January 7, 2019]. Arthritis Rheumatol. doi:10.1002/art.40814

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