In this study, we prospectively measured the SMT mass using cardiac MR imaging in a group of consecutive patients with known or suspected PH. Using hemodynamic findings obtained by RHC performed within hours of the imaging studies, we demonstrate that cardiac MR-derived SMT mass measurement is a novel and reproducible marker of PH. Using ROC analysis, SMT mass and VMI had a similar performance in diagnosing the presence or absence of PH. Both SMT mass and VMI were found to be significant, independent predictors of PH. SMT mass is readily assessed by cardiac MRI and is, in our experience, significantly less time-intensive than assessing VMI (less than a minute versus 10 minutes for post-processing time, respectively).
The measurement of SMT mass enabled identification of the presence or absence of PH with good accuracy, although the correlation of SMT mass with mPAP was not excellent (r=0.62). The study group included individuals with PH of different etiologies, but essentially patients with IPAH and scleroderma-associated PAH as well as a few patients with pulmonary venous hypertension, which reflects the natural mix of patients referred to our PH program for assessment of PH.
To our knowledge, this is the first study to systematically correlate the SMT mass assessed by MRI to invasive RHC findings in patients with known or suspected PH. Our study supports the hypothesis that the SMT-moderator complex functions not only as a conduction pathway, but also is involved in RV function mechanics. This complex appears to be an integral part of the RV remodeling process in PH, as suggested by significant correlations with RV mass and VMI parameters. We demonstrated that increased SMT mass correlated strongly with markers of RV dysfunction (): decreased RVEF and RV stroke volume and increased RVED and RVES volumes. Impaired RV function, and more recently increased VMI, have been linked to poor prognosis in patients with IPAH and scleroderma-associated PAH (17
). Future longitudinal studies will help determine whether increased SMT mass also predicts poor patient outcome.
The ability to diagnose PH using VMI tended to be superior compared to RV mass alone as a marker for PH, suggesting that the biventricular mass ratio is the most important factor in the detection of PH, compared to RV mass alone. This notion is supported by our findings that RV mass/BSA and LV mass/BSA are both independent predictors of PH. While RV mass/BSA had a significant positive correlation with mPAP (r=0.57, p<0.0001), LV mass/BSA tended to have a significant negative correlation with mPAP (r=-0.28, p=0.05), the latter finding being most likely related to interventricular dependence as well as poor venous return resulting in chronic underfilling of the LV in PAH. This is supported by significant negative correlations of PVRI with LVED/BSA (r=-0.59, p<0.0001), LVES/BSA (r=-0.55, p<0.0001) and LV stroke volume/BSA (r=-0.51, p=0.0004) in our patient population. These changes in opposite direction for RV mass/BSA and LV mass/BSA may explain why VMI tended to have a better performance than RV mass alone.
There are some limitations to our study. 31% (15 out of 49) of patients were on specific medical therapy for PH, which may have theoretically affected the remodeling of the SMT mass over time. Although there is very scant information on the effects of PH specific therapy on cardiac remodeling, sildenafil treatment has been shown to reduce RV mass and improve cardiac function over a period of 16 weeks (24
). However, since the majority of our patients were treatment naïve, it is unlikely that therapy might have affected assessment of cardiac mass (including SMT or VMI) and our overall analysis.
For ethical reasons, asymptomatic control subjects did not undergo RHC measurements to confirm the absence of PH. However, it is unlikely that any of the control subjects had PH, given that IPAH is a rare disease with a prevalence of about 2-3 per million (25
). In addition, none of our controls had clinical conditions known to be associated with PH. Also, there were no significant differences in SMT mass or VMI in patients who were found not to have PH by RHC, compared to normal controls. Therefore, it is very unlikely that we might have included individuals with PH in the control group.
Another limitation of this study relates to the fact that two different MR systems (1.5T and 3T), sequences (SSFP and turbo FLASH GRE), and vendors were used. Small differences in RV and LV function parameters at 1.5T and 3T between the newer SSFP and the turbo FLASH GRE sequence have been reported (26
). However, there is improved blood pool-to-wall contrast and fewer artifacts at 3T, compared to 1.5T, with the turbo FLASH GRE sequence compared to the SSFP sequence (29
). Also a separate ROC sub-analysis for all patients who underwent the 3T turbo FLASH cine MRI protocol did not show any significant differences when compared to the total cohort. Our VMI correlation with mPAP (r=0.72) and performance to detect PH (AUC=0.91) was similar to previously published data by Saba et al. (r=0.81, (9
)) and Hagger et al. (r=079, AUC=0.92, (17
)), demonstrating the consistency of our results with the published literature using only one MR imaging technique.
In conclusion, we have identified in the MRI-derived measurement of SMT mass a novel, reproducible and non-invasive marker of PH. VMI and SMT mass measurements by MRI were equally effective in detecting PH in our patient population, and both correlated well with indices of RV dysfunction. The value of SMT as a prognostic factor of outcome in PH and as a reliable end-point for response to therapy needs to be further investigated in adequately designed longitudinal studies.