Right Ventricular Remodeling in Idiopathic and Scleroderma‐Associated Pulmonary Arterial Hypertension: Two Distinct Phenotypes

Abstract

Patients with scleroderma (SSc)-associated pulmonary arterial hypertension (PAH) have worse survival than patients with idiopathic PAH (IPAH). We hypothesized that the right ventricle (RV) adapts differently in SSc-PAH versus IPAH. We used cardiac magnetic resonance imaging (cMRI) and hemodynamic characteristics to assess the relationship between RV morphology and RV load in patients with SSc-PAH and IPAH. In 53 patients with PAH (35 with SSc-PAH and 18 with IPAH) diagnosed by right heart catheterization (RHC), we examined cMRIs obtained within 48 hours of RHC and compared RV morphology between groups. Regression analysis was used to assess the association between diagnosis (IPAH vs. SSc-PAH) and RV measurements after adjusting for age, sex, race, body mass index (BMI), left ventricular (LV) mass, and RV load. There were no significant differences in unadjusted comparisons of cMRI measurements between the two groups. Univariable regression showed RV mass index (RVMI) was linearly associated with measures of RV load in both the overall cohort and within each group. Multivariable linear regression models revealed a significant interaction between disease type and RVMI adjusting for pulmonary vascular resistance (PVR), age, sex, race, BMI, and LV mass. This model showed a decreased slope in the relationship between RVMI and PVR in the SSc-PAH group compared with the IPAH group. RVMI varies linearly with measures of RV load. After adjusting for multiple potential confounders, patients with SSc-PAH demonstrated significantly less RV hypertrophy with increasing PVR than patients with IPAH. This difference in adaptive hypertrophy may in part explain previously observed decreased contractility and poorer survival in SSc-PAH.

Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension

“…Perhaps related, in a larger cohort, RV mass has been shown to be lower in SSc-PAH compared to IPAH when adjusted for pulmonary vascular load. 39 Other possibilities include weakened myocyte contractility and/or abnormal angiogenesis in SSc; these are being studied in an ongoing investigation.…”

Differences in right ventricular morphology, not function, indicate the nature of increased afterload in pulmonary hypertensive subjects with normal left ventricular function

“…12 However, the role of echocardiographic examination in PH has evolved in recent years. [13][14][15][16] Although RHC remains the standard for full hemodynamic assessment of PH, RHC is often applied only to subjects where clinical suspicion of PH PVD exits. 7 Given that the initial diagnosis is often delayed 2-3 years, it is likely that RHC is not utilized in many subjects with PH as a result of a lack of appreciation of the pathophysiology of the PH on the initial noninvasive assessment.…”

“…Transthoracic echocardiogram (TTE) is commonly used as a noninvasive PH screening tool by estimation of pulmonary artery systolic pressure (PASP) using continuous‐wave Doppler transtricuspid flow velocity . However, the role of echocardiographic examination in PH has evolved in recent years …”

Pulmonary arterial hypertension associated with connective tissue diseases: A review focusing on distinctive clinical aspects

“…A study performed by Mathai et al found increased serum N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels in SSc‐PAH patients compared with IPAH patients despite lower mean pulmonary arterial pressure (mPAP) in SSc‐PAH patients. Several studies using cardiac magnetic resonance imaging detected SSc‐PAH‐specific cardiac involvements, such as impaired right ventricle adaptation to the increased afterload and altered biventricular interplay . An endomyocardial biopsy study demonstrated abnormal myocardial collagen deposition in 15 (94%) of 16 SSc patients with no signs or symptoms of left or right heart disease .…”