Identification of differential gene expression related to epirubicin-induced cardiomyopathy in breast cancer patients.
- 作者列表："Peng J","Wang Z","Li Y","Lv D","Zhao X","Gao J","Teng H
BACKGROUND:Epirubicin is a potent chemotherapeutic agent for the treatment of breast cancer. However, it may lead to cardiotoxicity and cardiomyopathy, and no reliable biomarker was available for the early prediction of epirubicin-induced cardiomyopathy. METHODS:Global gene expression changes of peripheral blood cells were studied using high-throughput RNA sequencing in three pair-matched breast cancer patients (patients who developed symptomatic cardiomyopathy paired with patients who did not) before and after the full session of epirubicin-based chemotherapy. Functional analysis was conducted using gene ontology and pathway enrichment analysis. RESULTS:We identified 13 significantly differentially expressed genes between patients who developed symptomatic epirubicin-induced cardiomyopathy and their paired control who did not. Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5'-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis. CONCLUSIONS:ALAS2 and the metabolic pathways which were involved may play an important role in the development of epirubicin-induced cardiomyopathy. ALAS2 may be useful as an early biomarker for epirubicin-induced cardiotoxicity detection.
背景: 表阿霉素是治疗乳腺癌的有效化疗药物。然而，它可能导致心脏毒性和心肌病，并且没有可靠的生物标志物可用于表阿霉素诱导的心肌病的早期预测。 方法: 使用高通量 RNA 测序研究了三对配对乳腺癌患者 (发生症状性心肌病的患者与未发生症状的患者配对) 外周血细胞的整体基因表达变化以表阿霉素为基础的化疗全期前后。使用基因本体论和通路富集分析进行功能分析。 结果: 我们在发生表阿霉素诱导的症状性心肌病的患者和未发生的配对对照之间鉴定了 13 个显著差异表达的基因。其中，上调的 bcl-2 相关 X 蛋白与 “凋亡” 相关，而下调的 5 '-氨基酮戊酸合成酶 2 (ALAS2) 与 “甘氨酸、丝氨酸、途径富集分析中的“ 苏氨酸代谢 ”和“ 卟啉和叶绿素代谢 ”。 结论: ALAS2 及其参与的代谢途径可能在表阿霉素心肌病的发生发展中发挥重要作用。ALAS2 可能作为表阿霉素诱导心脏毒性检测的早期生物标志物。
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.