Dataset Information

A Novel Gene Signature to Predict Survival Time and Incident Ventricular Arrhythmias in Patients with Dilated Cardiomyopathy.

ABSTRACT: The mortality in nonischaemic dilated cardiomyopathy (NIDCM) patients is still at a high level; sudden death in NIDCM can be caused by ventricular tachycardia. It is necessary to explore the pathogenesis of ventricular arrhythmias (VA) in NIDCM. Differentially expressed genes (DEGs) were identified by comparing the gene expression of NIDCM patients with or without VA in the gene expression profile of GSE135055. A total of 228 DEGs were obtained, and 3 genes were screened out to be significantly related to the survival time of NIDCM patients. We established a prediction model on two-gene (TOMM22, PPP2R5A) signature for the survival time of NIDCM patients. The area under the curve (AUC) was 0.75 calculated by the ROC curve analysis. These risk genes are probably new targets for exploring the pathogenesis of NIDCM with VA; the prediction model for survival time and incident ventricular arrhythmias is useful in clinical decision making for individual treatment.

SUBMITTER: Ge C

PROVIDER: S-EPMC7512094 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Novel Gene Signature to Predict Survival Time and Incident Ventricular Arrhythmias in Patients with Dilated Cardiomyopathy.

Ge Chenliang C He Yan Y

Disease markers 20200915

The mortality in nonischaemic dilated cardiomyopathy (NIDCM) patients is still at a high level; sudden death in NIDCM can be caused by ventricular tachycardia. It is necessary to explore the pathogenesis of ventricular arrhythmias (VA) in NIDCM. Differentially expressed genes (DEGs) were identified by comparing the gene expression of NIDCM patients with or without VA in the gene expression profile of GSE135055. A total of 228 DEGs were obtained, and 3 genes were screened out to be significantly ...[more]

PMID: 33014188

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Project description:AimsPatients with non-ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter-defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM.Methods and resultsWe searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow-up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74-1.00)], hypertension [HR 1.95; 95% CI (1.26-3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32-13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19-1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02-7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non-sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin-C (FLNC)] were associated with arrhythmic outcome in non-pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high.ConclusionsIn patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non-)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter-defibrillator implantation.

Project description:Background: The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Methods: Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. Results: There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Conclusions: Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.

Dataset Information

A Novel Gene Signature to Predict Survival Time and Incident Ventricular Arrhythmias in Patients with Dilated Cardiomyopathy.

Publications

A Novel Gene Signature to Predict Survival Time and Incident Ventricular Arrhythmias in Patients with Dilated Cardiomyopathy.

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