الفهرس 
Acknowledgements
Pulmonary arterial hypertension (PAH)Only 14 pages are availabe for public view
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Abstract
124 Patients from all clinical groups of RHC-proven PH who had a CMR scan with contrast between January 2008 and June 2014 at Allegheny General Hospital, Temple University School of Medicine, Pittsburgh, PA, were retrospectively included.The RHC parameters were included in the analysis only if it was performed within 6 months of their CMR scan (average time lapse was 1±2 months).
The following parameters derived from RCH were considered for each patient: mean pulmonary arterial pressure (mPAP), systolic and diastolic RV pressures (sRVP and dRVP), mean right atrial pressure (mRAP), pulmonary vascular resistance index (PVRI), and mixed venous oxygen saturation (MVO2).
The following volumetric and functional CMR parameters were obtained from the medical records for each patient: RV end-systolic volume (RVESV), RV stroke volume derived by phase velocity mapping (RVSV by PVM), RV ejection fraction (RVEF) and RV mass (RVM).The short-axis (SA) LGE images were then evaluated for the amount/extent of LGE in RVIPs and IVS.
Medical records were reviewed for a composite MACE end-point of 1) initiating IV prostacyclin therapy, 2) hospitalization for heart failure, 3) referral for lung transplantation, 4) life-threatening ventricular arrhythmias, and 5) death. All deaths were confirmed by the social security death index.
Follow-up CMR studies for 44/124 pts. (35%) were further evaluated. The very latest CMR scan for each individual patient was considered. The time lapse from the index CMR scan to the follow-up scan was on average 21±14 months.
Ea/Emax (RVESV divided by RVSV), RVIW (RVESV× [sRVP-dRVP]), RVIP LGE and delta RVIP LGE and other progonostically-established parameters were evaluated for impact on outcome. Logistic and Cox regression analysis of selected variables that correlated to outcome were employed.
The following were univariate predictors of MACE: mRAP (odds ratio [OR]=1.07; CI=1.02 to 1.13, P=0.01), RVESV (OR=1.009; CI=1.003 to 1.014, P=0.002), RVEF (OR=0.97; CI=0.942 to 0.995, P=0.02), Ea/Emax (OR=1.46; CI=1.09 to 1.973, P=0.01), and RV internal mechanical work (OR=1.000126; CI=1.000044 to 1.000207, P=0.002). However, on multivariate regression analysis only RVESV retained its predictive ability (OR=1.011; CI=1.004 to 1.018, P=0.002).
The following were univariate predictors of time to MACE:mRAP (HR=1.06; CI= 1.03 to 1.09; P<0.001), RVESV (HR=1.01; CI=1.006 to 1.014; P<0.001), RVEF (HR=0.97; CI=0.93 to 0.99; P=0.004),Ea/Emax (HR=1.44; CI=1.19 to 1.75; P<0.001), RV internal mechanical work (HR=slightly above 1; P<0.001), and MVO2 (HR=0.95; CI=0.92 to 0.98; P=0.004). However, on multivariate regression analysis only RVESV (HR=1.007; CI=1.003 to 1.012, P=0.001) and mRAP (HR=1.045, CI=1.012-1.078, P=0.006) retained their predictive ability.
Neither RVIP LGE % nor whole IVS LGE % predicted MACE (P=0.66 and 0.69 respectively) nor time to MACE (P=0.66 and 0.63 respectively).
Upon stratifying the study population into two groups using the cut-off proposed by Vanderpoolet al.225 (Ea/Emax of ≥1.94175); a significant very early split in time to MACE was evident and progressed over time (Log Rank χ2=5.31; P=0.021, Generalized Wilcoxon χ2=6.382; P=0.012, Taron-Ware χ2=5.897; P=0.015).
Upon stratifying the study population into two groups using an ROC-derived RVESV cut-off of ≥96 mL; a significant split in time to MACE appeared (Log Rank χ2=5.03; P=0.025, Generalized Wilcoxon χ2=5.843; P=0.016, Taron-Ware χ2=5.373); particularly in the first 170 days of follow-up.
Not only is delta LGE static or incremental but it could decrease over time. This is the first study to our knowledge to address this concept in PH patients.
On Cox proportional hazard regression analysis, ΔLGE was not a significant predictor of time to MACE (P=0.77). However, there is a dichotomy in time to MACE approaching statistical significance (log rank test X2=1.93; df=1; P=0.165) between those who achieved a tangible reduction of RVIP LGE% (reduction of ≥1.9701 in LGE %) and those who did not.
The mere visual assessment of LGE showed a reasonable agreement with LGE quantification
Therefore, we conclude the following:
1. Both RV internal mechanical work and Ea/Emax are physiologically sound and clinically feasible predictors of outcome in PH patients and equivalent if not superior to standard clinical metrics such as RV EF;Ea/Emaxhaving the advantage of being an entirely non-invasive MRI-based derivation.
2. The previously proposed cut-off for Ea/Emax of 1.94 (≈2) has been further validated in this study and can be used in practice to risk-stratify PH patients.
3. 3D RVESV is a major predictor of outcome in PH patients (an increase of 1 mL is equivalent to 1% increase in risk of MACE and shorter time to MACE) and superior to volumetric Ea/Emax, RV internal mechanical work, as well as standard clinical metrics such as RV EF. RVESV has the advantage of being an entirely non-invasive MRI-based measurement.
4. Neither a single time-point RVIP nor whole IVS LGE % can predict outcome in PH patients but, rather, the change over time holds some prognostic potential. This combined with the observation that RVIP LGE % is not only static or incremental but can decrease over time as well, suggests that for the biggest part it is not replacement fibrosis (scar). >5 Failure of RVIP LGE % to tangibly decline over time portends worse outcome in PH patients.6 Naked-eye visual assessment of RVIP LGE is a reasonable surrogate of its formal quantification.