Fibrosis in Arrhythmogenic Cardiomyopathy: The Phantom Thread in the Fibro-Adipose Tissue
- 作者列表："Angela Serena Maione","Chiara Assunta Pilato","Michela Casella","Alessio Gasperetti","Alessio Gasperetti","Ilaria Stadiotti","Giulio Pompilio","Giulio Pompilio","Elena Sommariva
Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disorder, predisposing to malignant ventricular arrhythmias leading to sudden cardiac death, particularly in young and athletic patients. Pathological features include a progressive loss of myocardium with fibrous or fibro-fatty substitution. During the last few decades, different clinical aspects of ACM have been well investigated but still little is known about the molecular mechanisms that underlie ACM pathogenesis, leading to these phenotypes. In about 50% of ACM patients, a genetic mutation, predominantly in genes that encode for desmosomal proteins, has been identified. However, the mutation-associated mechanisms, causing the observed cardiac phenotype are not always clear. Until now, the attention has been principally focused on the study of molecular mechanisms that lead to a prominent myocardium adipose substitution, an uncommon marker for a cardiac disease, thus often recognized as hallmark of ACM. Nonetheless, based on Task Force Criteria for the diagnosis of ACM, cardiomyocytes death associated with fibrous replacement of the ventricular free wall must be considered the main tissue feature in ACM patients. For this reason, it urges to investigate ACM cardiac fibrosis. In this review, we give an overview on the cellular effectors, possible triggers, and molecular mechanisms that could be responsible for the ventricular fibrotic remodeling in ACM patients.
致心律失常性心肌病 (ACM) 是一种遗传性心脏病，易发生恶性室性心律失常，导致心源性猝死，尤其是年轻和运动患者。病理特征包括纤维或纤维脂肪替代的心肌进行性丧失。在过去的几十年里，ACM 的不同临床方面已经得到了很好的研究，但是对于 ACM 发病机制的分子机制仍然知之甚少，导致了这些表型。在大约 50% 的 ACM 患者中，已经确定了一个基因突变，主要是编码桥粒蛋白的基因。然而，引起观察到的心脏表型的突变相关机制并不总是清楚的。到目前为止，人们的注意力主要集中在导致心肌脂肪替代的分子机制的研究上，脂肪替代是心脏疾病的一种不常见的标志物，因此通常被认为是 ACM 的标志。尽管如此，基于工作组诊断 ACM 的标准，与心室游离壁纤维置换相关的心肌细胞死亡必须被认为是 ACM 患者的主要组织特征。出于这个原因，它敦促研究 ACM 心脏纤维化。在这篇综述中，我们概述了 ACM 患者心室纤维化重构的细胞效应因子、可能的触发因素和分子机制。
METHODS:Abstract Background Ischemic cardiomyopathy is a high-cost, resource-intensive public health burden that is associated with a 1-year mortality rate of about 16% in western population. Different in patient ethnicity and pattern of practice may impact the clinical outcome. We aim to determine 1-year mortality and to identify factors that significantly predicts 1-year mortality of Thai patients with ischemic cardiomyopathy. Methods This prospective multicenter registry enrolled consecutive Thai patients that were diagnosed with ischemic cardiomyopathy at 9 institutions located across Thailand. Patients with left ventricular function 75% in the left main or proximal left anterior descending artery or coronary angiography, and/or two major epicardial coronary stenoses; 2) prior myocardial infarction; 3) prior revascularization by coronary artery bypass graft or percutaneous coronary intervention; or, 4) magnetic resonance imaging pattern compatible with ischemic cardiomyopathy. Baseline clinical characteristics, coronary and echocardiographic data were recorded. The 1-year clinical outcome was pre-specified. Results Four hundred and nineteen patients were enrolled. Thirty-nine patients (9.9%) had died at 1 year, with 27 experiencing cardiovascular death, and 12 experiencing non-cardiovascular death. A comparison between patients who were alive and patients who were dead at 1 year revealed lower baseline left ventricular ejection fraction (LVEF) (26.7 ± 7.6% vs 30.2 ± 7.8%; p = 0.021), higher left ventricular end-diastolic volume (LVEDV) (185.8 ± 73.2 ml vs 155.6 ± 64.2 ml; p = 0.014), shorter mitral valve deceleration time (142.9 ± 57.5 ml vs 182.4 ± 85.7 ml; p = 0.041), and lower use of statins (94.7% vs 99.7%; p = 0.029) among deceased patients. Patients receiving guideline-recommended β-blockers had lower mortality than patients receiving non-guideline-recommended β-blockers (8.1% vs 18.2%; p = 0.05). Conclusions The results of this study revealed a 9.9% 1-year mortality rate among Thai ischemic cardiomyopathy patients. Doppler echocardiographic parameters significantly associated with 1-year mortality were LVEF, LVEDV, mitral E velocity, and mitral valve deceleration time. The use of non-guideline-recommended β-blockers rather than guideline recommended β-blockers were associated with increased with 1-year mortality. Guidelines recommended β-blockers should be preferred. Trial registration Thai Clinical Trials Registry TCTR20190722002. Registered 22 July 2019. “Retrospectively registered”.
METHODS:Abstract Background Peripartum cardiomyopathy (PPCM) is rare and potentially life-threatening; its etiology remains unclear. Imaging characteristics on cardiovascular magnetic resonance (CMR) and their prognostic significance have rarely been studied. We sought to determine CMR’s prognostic value in PPCM by using T1 and T2 mapping techniques. Methods Data from 21 PPCM patients from our CMR registry database were analyzed. The control group comprised 20 healthy age-matched females. All subjects underwent comprehensive contrast-enhanced CMR. T1 and T2 mapping using modified Look-Locker inversion recovery and T2 prep balanced steady-state free precession sequences, respectively. Ventricular size and function, late gadolinium enhancement (LGE), myocardial T1 value, extracellular volume (ECV), and T2 value were analyzed. Transthoracic echocardiography was performed at baseline and during follow-up. The recovered left ventricular ejection fraction (LVEF) was defined as LVEF ≥50% on echocardiography follow-up after at least 6 months of the diagnosis. Results CMR imaging showed that the PPCM patients had severely impaired LVEF and right ventricular ejection fraction (LVEF: 26.8 ± 10.6%; RVEF: 33.9 ± 14.6%). LGE was seen in eight (38.1%) cases. PPCM patients had significantly higher native T1 and ECV (1345 ± 79 vs. 1212 ± 32 ms, P < 0.001; 33.9 ± 5.2% vs. 27.1 ± 3.1%, P < 0.001; respectively) and higher myocardial T2 value (42.3 ± 3.7 vs. 36.8 ± 2.3 ms, P < 0.001) than did the normal controls. After a median 2.5-year follow-up (range: 8 months-5 years), six patients required readmission for heart failure, two died, and 10 showed left ventricular function recovery. The LVEF-recovered group showed significantly lower ECV (30.7 ± 2.1% vs. 36.8 ± 5.6%, P = 0.005) and T2 (40.6 ± 3.0 vs. 43.9 ± 3.7 ms, P = 0.040) than the unrecovered group. Multivariable logistic regression analysis showed ECV (OR = 0.58 for per 1% increase, P = 0.032) was independently associated with left ventricular recovery in PPCM. Conclusions Compared to normal controls, PPCM patients showed significantly higher native T1, ECV, and T2. Native T1, ECV, and T2 were associated with LVEF recovery in PPCM. Furthermore, ECV could independently predict left ventricular function recovery in PPCM.
METHODS:BACKGROUND:Atrial fibrillation (AF) is the most common arrhythmia in hypertrophic cardiomyopathy (HCM) and is associated with adverse outcomes in HCM patients. Although the left atrial (LA) diameter has consistently been identified as a strong predictor of AF in HCM patients, the relationship between LA dysfunction and AF still remains unclear. The aim of this study is to evaluate the LA function in patients with non-obstructive HCM (NOHCM) utilizing cardiovascular magnetic resonance feature tracking (CMR-FT).,METHODS:Thirty-three patients with NOHCM and 28 healthy controls were studied. The global and regional LA function and left ventricular (LV) function were compared between the two groups. The following LA global functional parameters were quantitively analyzed: reservoir function (total ejection fraction [LA total EF], total strain [ε], peak positive strain rate [SRs]), conduit function (passive ejection fraction [LA passive EF], passive strain [ε], peak early-negative SR [SRe]), and booster pump function (active ejection fraction [LA active EF], active strain [ε], peak late-negative SR [SRa]). The LA wall was automatically divided into 6 segments: anterior, antero-roof, inferior, septal, septal-roof and lateral. Three LA strain parameters (ε, ε, ε) and their corresponding strain rate parameters (SRs, SRe, SRa) during the reservoir, conduit and booster pump LA phases were segmentally measured and analyzed.,RESULTS:The LA reservoir (LA total EF: 57.6 ± 8.2% vs. 63.9 ± 6.4%, p < 0.01; ε: 35.0 ± 12.0% vs. 41.5 ± 11.2%, p = 0.03; SRs: 1.3 ± 0.4 s vs. 1.5 ± 0.4 s, p = 0.02) and conduit function (LA passive EF: 28.7 ± 9.1% vs. 37.1 ± 10.0%, p < 0.01; ε: 18.7 ± 7.9% vs. 25.9 ± 10.0%, p < 0.01; SRe: - 0.8 ± 0.3 s vs. -1.1 ± 0.4 s, p < 0.01) were all impaired in patients with NOHCM when compared with healthy controls, while LA booster pump function was preserved. The LA segmental strain and strain rate analysis demonstrated that the ε, ε, SRe of inferior, SRs, SRe of septal-roof, and SRa of antero-roof walls (all p < 0.05) were all decreased in the NOHCM cohort. Correlations between LA functional parameters and LV conventional function and LA functional parameters and baseline parameters (age, body surface area and NYHA classification) were weak. The two strongest relations were between ε and LA total EF(r = 0.84, p < 0.01), ε and LA active EF (r = 0.83, p < 0.01).,CONCLUSIONS:Compared with healthy controls, patients with NOHCM have LA reservoir and conduit dysfunction, and regional LA deformation before LA enlargement. CMR-FT identifies LA dysfunction and deformation at an early stage.