The impact of ambrisentan and tadalafil upfront combination therapy on cardiac function in scleroderma associated pulmonary arterial hypertension patients: cardiac magnetic resonance feature tracking study

Takahiro Sato, Bharath Ambale-Venkatesh, Joao A C Lima, Stefan L Zimmerman, Ryan J Tedford, Tomoki Fujii, Olivia L Hulme, Erica H Pullins, Celia P Corona-Villalobos, Roham T Zamanian, Omar A Minai, Reda E Girgis, Kelly Chin, Rubina Khair, Rachel L Damico, Todd M Kolb, Stephen C Mathai, Paul M Hassoun, Takahiro Sato, Bharath Ambale-Venkatesh, Joao A C Lima, Stefan L Zimmerman, Ryan J Tedford, Tomoki Fujii, Olivia L Hulme, Erica H Pullins, Celia P Corona-Villalobos, Roham T Zamanian, Omar A Minai, Reda E Girgis, Kelly Chin, Rubina Khair, Rachel L Damico, Todd M Kolb, Stephen C Mathai, Paul M Hassoun

Abstract

The aim of this study was to evaluate the effect of upfront combination therapy with ambrisentan and tadalafil on left ventricular (LV) and right ventricular (RV) function in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). LV and RV peak longitudinal and circumferential strain and strain rate (SR), which consisted of peak systolic SR (SRs), peak early diastolic SR (SRe), and peak atrial-diastolic SR (SRa) were analyzed using cardiac magnetic resonance imaging (CMRI) data from the recently published ATPAHSS-O trial (ambrisentan and tadalafil upfront combination therapy in SSc-PAH). Twenty-one patients completed the study protocol. Measures of RV systolic function (RV free wall [RVFW] peak longitudinal strain [pLS], RVFW peak longitudinal SRs [pLSRs]) and RV diastolic function (RVFW peak longitudinal SRa [pLSRa], RVFW peak circumferential SRe) were improved after treatment. LV systolic function (LV peak global longitudinal strain [pGLS]) and diastolic function (LV peak global longitudinal SRe [pGLSRe]) were also significantly improved at follow-up. Increased 6-min walk distance was significantly correlated with RVFW pLS and pLSRs, while the decrease in N-terminal pro-brain natriuretic peptide was correlated with LV pGLS. Increased cardiac index was associated with improved LV pGLSRe, and reduction in mean right atrial pressure was correlated with improved RVFW pLS and pLSRa. Combination therapy was associated with a significant improvement in both RV and LV function as assessed by CMR-derived strain and SR. Importantly, the improvement in RV and LV strain and SR correlated with improvements in known prognostic markers of PAH. (Approved by clinicaltrials.gov [NCT01042158] before patient recruitment.).

Keywords: cardiac magnetic resonance imaging; combination therapy; pulmonary arterial hypertension; strain and strain rate; systemic sclerosis.

Figures

Fig. 1.
Fig. 1.
Representative images of peak SRs and peak SR analysis. RV and LV measurements by tissue-tracking CMR in a patient with scleroderma-associated PAH. (a) RV peak longitudinal strain and SR measurement in four-chamber view. (b) RV peak circumferential strain and SR measurement in the short-axis view at the mid-level RVFW and LVFW were traced as a whole. After that we confirmed six segments then we excluded three of the LVFW segments. (c, d) LV peak global longitudinal strain in the two- and four-chamber views at the end of LV systole. (e) LV pLS and SR analysis in four-chamber view. (F) LV peak circumferential strain and SR in the short-axis view at the mid-level.
Fig. 2.
Fig. 2.
Representative curves of strain and SR (e.g. RV longitudinal strain and SR analysis). Peak systolic strain was identified from the strain curve (a). Peak SRs, peak SRe, and peak SRa were also analyzed from the SR curve (b).
Fig. 3.
Fig. 3.
Correlations between clinical parameters and CMR-derived peak systolic strain and peak SR parameters. Correlation between changes in 6MWD, NT-proBNP, and hemodynamic parameters, and CMR-derived strain and SR parameters from baseline to 36 weeks. 6MWD, 6-min walk distance; NT-proBNP, N Terminal pro-brain natriuretic peptide; CI, cardiac index; RAP, right atrial pressure; mPAP, mean pulmonary arterial pressure; PVR, pulmonary vascular resistance; SV, stroke volume; RV, right ventricular; LV, left ventricular; EF, ejection fraction; L, longitudinal; C, circumferential; GL, global; SRs, peak systolic strain rate; SRe, peak early diastolic strain rate; SRa, peak atrial-diastolic strain rate.

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Source: PubMed

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