Predictive role of quantification of myocardial fibrosis using delayed contrast-enhanced magnetic resonance imaging in nonischemic dilated cardiomyopathies: a systematic review and meta-analysis

Aim. The present study aims to provide a systematic review and meta-analysis to investigate the prognostic role of assessing the severity of myocardial fibrosis using delayed contrast-enhanced magnetic resonance imaging in nonischemic dilated cardiomyopathies.Material and methods. We searched PubMed, Google Scholar for studies that examined the predictive value of quantifying late gadolinium enhancement (LGE) areas in patients with nonischemic dilated cardiomyopathy. Unadjusted hazard ratios (HR) from studies with similar scoring criteria were pooled for meta-analysis.Results. Nine studies were retrieved from 782 publications for this systematic review and meta-analysis. In total, 2389 patients (mean age, 51,9 years; mean follow-up, 39,3 months) were included in the analysis. Meta-analysis showed the extent of LGE was associated with an increased risk of arrhythmic end point (HR: 1,09/1% LGE; 95% CI: 1,02-1,18; p=0,01), major adverse cardiovascular events (HR: 1,07/1% LGE; 95% CI: 1,01-1,13; p=0,03) and all-cause mortality (HR: 1,09/1% LGE; 95% CI: 1,04-1,13; p<0,0001).Conclusion. The severity of LGE by cardiac magnetic resonance predicts arrhythmic events (ventricular arrhythmia and sudden death), major adverse cardiovascular events and all-cause mortality. Assessment of LGE can be used as an effective tool for stratifying risk in patients with nonischemic dilated cardiomyopathy.

Clinical Outcomes of Autologous Stem Cell–Patch Implantation for Patients With Heart Failure With Nonischemic Dilated Cardiomyopathy

Background Clinical effectiveness of autologous skeletal cell‐patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty‐four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches were implanted over the surface of the left ventricle through left minithoracotomy without procedure‐related complications and lethal arrhythmia. We identified 13 responders and 11 nonresponders using the combined indicator of a major cardiac adverse event and incidence of heart failure event. In the responders, symptoms, exercise capacity, and cardiac performance were improved postoperatively (New York Heart Association class II 7 [54%] and III 6 [46%] to New York Heart Association class II 12 [92%] and I 1 [8%], P <0.05, 6‐minute walk test; 471 m [370–541 m] to 525 m [425–555 m], P <0.05, left ventricular stroke work index; 31.1 g·m 2 ·beat [22.7–35.5 g·m 2 ·beat] to 32.8 g·m 2 ·beat [28–38.5 g·m 2 ·beat], P =0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B‐type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B‐type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: ​OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic–area under the curve, 0.96, P <0.001). Conclusions This clinical trial demonstrated that autologous skeletal stem cell–patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility. Registration URL: http://www.umin.ac.jp/english/ . Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892.

Beneficial Effect of Left Ventricular Remodeling after Early Change of Sacubitril/Valsartan in Patients with Nonischemic Dilated Cardiomyopathy

Background and Objectives: Evidence for effectiveness of early change from angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) to sacubitril/valsartan is lacking. We aimed to investigate whether early changes to sacubitril/valsartan could improve outcomes in patients with nonischemic dilated cardiomyopathy (DCM) in real-world practice. Materials and Methods: A total of 296 patients with nonischemic DCM who were treated with ARB or ACEI continuously (group A, n = 150) or had their medication switched to sacubitril/valsartan (group S, n = 146) were included. The sacubitril/valsartan group was divided into early change (within 60 days, group S/E, n = 59) and late change (group S/L, n = 87) groups. Changes in echocardiographic parameters from the time of initial diagnosis to the last follow-up were analyzed. Results: Patients in group S showed greater left ventricular (LV) end-diastolic dimension (EDD) (group A vs. S, 61.7 ± 7.4 vs. 66.5 ± 8.0, p < 0.001) and lower LV ejection fraction (LVEF) (28.9 ± 8.2% vs. 23.9 ± 7.5%, p < 0.001) than those in group A at initial diagnosis. During a median follow-up of 76 months, patients in group S/E, ∆ LVEF (%) and ∆ LVESD (mm) were significantly improved compared with those in patients in group A (group A vs. S/E, ∆ LVEF, p = 0.036; ∆ LVESD, p = 0.023) or S/L (group S/E vs. S/L, ∆ LVEF, p = 0.05; ∆ LVESD, p = 0.005). Among patients whose medications were switched to sacubitril/valsartan, those with an earlier change showed a significant correlation with greater LVEF improvement (r = −0.367, p < 0.001) and LV reverse remodeling (r = 0.277, p < 0.001). Conclusions: in patients with nonischemic DCM, an early switch to sacubitril/valsartan was associated with greater improvement in LV function. Patients might benefit in terms of LV function by early switching to sacubitril/valsartan.