Serial Myocardial Native T1 Assessment for Prediction of LV Functional Recovery in Recent-Onset DCM: A Comparison with Histology

概要

Despite advances in heart failure therapies, the mortality rates of dilated cardiomyopathy (DCM) remain high and it is a leading cause of heart transplantation. Considering LV functional recovery is a pivotal process associated with better prognosis and a potential therapeutic target in DCM, a better understanding of myocardial tissue remodeling may be of great importance and inform a faster pathway for development of newer heart failure therapies.

Thirty patients (mean age; 49 years, 20 [67%] males) with recent-onset DCM and NYHA functional class  II were enrolled onto a study protocol approved by our Institutional Review Board. A retrospective review of 14 patients with clinically ordered scans before and after optimal medical therapy and prospective data from 16 patients were analyzed in this study. A written informed consent or an opt-out informed consent was obtained from all study participants. All patients underwent CMR, coronary angiography and myocardial biopsy at baseline and follow-up CMR [11 months (IQR; 7-30)] after initiation of optimal medical therapy. Neuro-hormonal antagonists were introduced and up-titrated for every patient. No patients received ICD/CRT implantation before the follow-up imaging. Imaging was performed utilizing a 3T MR system incorporating cine MR, late gadolinium enhancement (LGE), and triple-slice T1 mapping by MOLLI sequence. T1 measurements were performed on the septal myocardium at the mid-ventricular level without LGE enhancement. LGE volume was measured using the full- width at half-maximum method. Biopsy samples were stained with picrosirius red to determine collagen volume fraction (CVF). A paired Student`s t-test or Wilcoxon sign-rank test were used, as appropriate, to compare continuous variables at baseline and follow-up. Pearson`s or Spearman`s correlation coefficient was used to examine possible relationships among LV function, histological CVF and CMR T1 mapping findings. Intra- and inter-observer reliability of native T1 measurements were assessed with the intraclass correlation coefficient (ICC). All tests were 2-sided and p-values <0.05 were considered significant.

Figure 1A depicts representative cases with and without LV functional recovery. Native T1 decreased from 1376 ± 55 ms to 1312 ± 78 ms after medical therapy (change of native T1; -61

± 60 ms, p<0.001), and 4/30 (13%) patients had no improvement at follow-up. The change of native T1 after adjustment for baseline native T1 moderately correlated with an absolute LVEF increase (r=-0.35, p=0.07) and relative percent decrease of indexed LVEDV (r=0.46, p=0.01) and LVESV (r=0.46, p=0.01) (Figure 1B). Each 5 percentage decrease in native T1 was associated with a 12% and 17% reduction in indexed LVEDV and LVESV, respectively. The change of native T1 was not associated with baseline native T1, while it trended to be lower in patients with LGE (p=0.13). In addition, native T1 and extracellular volume fraction (ECV) at baseline similarly and moderately correlated with absolute LVEF increase (r=-0.54, -0.52, respectively, both p<0.05) and relative percent decrease of indexed LVEDV (r=0.44, 0.42, respectively, both p<0.05) and LVESV (r=0.52, 0.51, respectively, both p<0.05), while histological CVF correlated with none of them (r=-0.31, 0.13, 0.26). LGE was observed in 19/30 (63%) patients. The extent of LGE, but not the presence or location of LGE, was associated with the prevalence of LV functional recovery (p=0.01). None of the 6 patients with LGE volume ≥5.0% had LV functional recovery. The ICCs for inter-observer and intra-observer measurements of native T1 were 0.94 (95% CI: 0.88 to 0.97) and 0.97 (95% CI: 0.94 to 0.99), respectively.

We found that 26/30 (87%) patients showed a decrease in native T1 between baseline and follow-up, and patients with a greater reduction in native T1 displayed greater improvements in LVEF and more substantial reductions of indexed LVEDV and LVESV. In a study by Díez et al., some angiotensin receptor blockers (ARBs), such as losartan, induced regression of myocardial fibrosis in hypertensive patients.1 Thus, these differences might be partially explained by regression of diffuse myocardial fibrosis after medical therapy. Actually, 82% (9/11) of patients receiving follow-up ECV assessment showed a decrease in ECV between baseline and follow- up, with an absolute ECV decrease of -2.3%. Studies have demonstrated that DCM is associated with microvascular dysfunction, which correlates with the degree of LV function. There is a close association between elevated native T1 and myocardial ischemia in patients with coronary artery disease.2 A decrease in native T1 might also reflect improved microvascular dysfunction. Further studies are needed to confirm what a decrease in native T1 after medical therapy means and how best to use it in clinical practice. Given the high reproducibility of T1 assessment, serial native T1 assessment would enable the cardiologist to adopt a more tailored approach, allowing closer follow-up and more rapid escalation of therapy for patients at higher risk for progressive LV dilatation and LVEF decline and vice versa for those at lower risk.