Nonischemic Cardiomyopathy Etiology Research Articles

Bioinformatics analysis and identification of potential key genes and pathways in the pathogenesis of nonischemic cardiomyopathy.

Nonischemic cardiomyopathy (NICM) is a major cause of advanced heart failure, and the morbidity and mortality associated with NICM are serious medical problems. However, the etiology of NICM is complex and the related mechanisms involved in its pathogenesis remain unclear. The microarray datasets GSE1869 and GSE9128 retrieved from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs) between NICM and normal samples. The co-expressed genes were identified using Venn diagrams. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene ontology enrichment were used to clarify biological functions and signaling pathways. Analysis of protein-protein interaction networks using Search Tool for the Retrieval of Interacting Genes/Proteins online to define the hub genes associated with NICM pathogenesis. A total of 297 DEGs were identified from GSE1869, 261 of which were upregulated genes and 36 were downregulated genes. A total of 360 DEGs were identified from GSE9128, 243 of which were upregulated genes and 117 were downregulated genes. In the 2 datasets, the screening identified 36 co-expressed DEGs. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis showed that DEGs were mainly enriched in pantothenate and CoA biosynthesis, beta-alanine metabolism, kinetochore, G-protein beta/gamma-subunit complex, and other related pathways. The PPI network analysis revealed that DUSP6, EGR1, ZEB2, and XPO1 are the 4 hub genes of interest in the 2 datasets. Bioinformatics analysis of hub genes and key signaling pathways is an effective way to elucidate the mechanisms involved in the development of NICM. The results will facilitate further studies on the pathogenesis and therapeutic targets of NICM.

Outcomes of Catheter Ablation of Ventricular Tachycardia Based on Etiology in Nonischemic Heart Disease: An International Ventricular Tachycardia Ablation Center Collaborative Study.

This study sought to characterize ventricular tachycardia (VT) ablation outcomes across nonischemic cardiomyopathy (NICM) etiologies and adjust these outcomes by patient-related comorbidities that could explain differences in arrhythmia recurrence rates. Outcomes of catheter ablation of VT in patients with NICM could be related to etiology of NICM. Data from 2,075 patients with structural heart disease referred for catheter ablation of VT from 12 international centers was retrospectively analyzed. Patient characteristics and outcomes were noted for the 6 most common NICM etiologies. Multivariable Cox proportional hazards modeling was used to adjust for potential confounders. Of 780 NICM patients (57 ± 14 years of age, 18% women, left ventricular ejection fraction 37 ± 13%), underlying prevalence was 66% for dilated idiopathic cardiomyopathy (DICM), 13% for arrhythmogenic right ventricular cardiomyopathy (ARVC), 6% for valvular cardiomyopathy, 6% for myocarditis, 4% for hypertrophic cardiomyopathy, and 3% for sarcoidosis. One-year freedom from VT was 69%, and freedom from VT, heart transplantation, and death was 62%. On unadjusted competing risk analysis, VT ablation in ARVC demonstrated superior VT-free survival (82%) versus DICM (p≤ 0.01). Valvular cardiomyopathy had the poorest unadjusted VT-free survival, at 47% (p< 0.01). After adjusting for comorbidities, including age, heart failure severity, ejection fraction, prior ablation, and antiarrhythmic medication use, myocarditis, ARVC, and DICM demonstrated similar outcomes, whereas hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis had the highest risk of VT recurrence. Catheter ablation of VT in NICM is effective. Etiology of NICM is a significant predictor of outcomes, with ARVC, myocarditis, and DICM having similar but superior outcomes to hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis, after adjusting for potential covariates.

Should Primary Prevention ICDs Still Be Placed in Patients with Non-ischemic Cardiomyopathy? A Review of the Evidence

Recent evidence has suggested that implantable defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit in the presence of guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT). Despite significant benefits of GDMT and CRT, current evidence is derived from ICD trials that rely predominantly on reduced left ventricular ejection fraction alone (LVEF). The majority of patients with sudden cardiac death (SCD) have LVEF > 30% indicating that LVEF by itself is an inadequate predictor of SCD. The Danish study to assess the efficacy of ICD in patients with non-ischemic systolic heart failure on mortality (DANISH) highlights the importance of better risk stratifying NICM patients for ICD implantation. Assessment of life expectancy, comorbidities, presence of advanced heart failure, etiology of NICM, and the presence of myocardial fibrosis can help risk stratify ICD beyond LVEF. Genetics and biomarkers can be of further assistance in risk stratification.

Sudden cardiac death in nonischemic cardiomyopathy: Refining risk assessment.

Sudden cardiac death (SCD) risk assessment among patients with nonischemic cardiomyopathy (NICM) has been has been less straightforward than for patients with ischemic cardiomyopathy. The common surrogate that has been associated with highest SCD risk for all cardiomyopathies, and which has been universally used to guide implantation of primary-prevention implantable cardioverter-defibrillators (ICDs), is left ventricular ejection fraction (LVEF) ≤35%. However, this practice has been called into question, especially in light of recent trials suggesting that ICD treatment may not be of additional survival benefit among those with NICM treated with optimal medical therapy. This Clinical Review attempts to offer refinements to the current practice of SCD risk assessment among patients with NICM, with specific focus on importance of NICM etiology and efforts to identify myocardial scarring and arrhythmogenic substrate, both of which may provide greater information about SCD risk than the LVEF alone. These concepts are illustrated further as they apply to hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and cardiac sarcoidosis, all of which are increasingly recognized NICM substrates associated with SCD and for which refinements for assessing risk are lacking in conventional guidelines.

Myocardial Fibrosis Assessment by LGE Is a Powerful Predictor of Ventricular Tachyarrhythmias in Ischemic and Nonischemic LV Dysfunction: A Meta-Analysis

ObjectivesThe authors performed a meta-analysis to evaluate the predictive value of late gadolinium enhancement (LGE) cardiac magnetic resonance for ventricular tachyarrhythmia in ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients with ventricular dysfunction. BackgroundThe use of LGE to detect myocardial fibrosis and its related arrhythmic substrate is well established. Several recent studies have described the predictive value of LGE for ventricular tachyarrhythmias; however, their validity is limited by small sample size and low number of events. MethodsMEDLINE and the Cochrane Library electronic databases were systematically searched to identify studies that applied LGE in ICM and NICM patients with ventricular dysfunction and reported arrhythmic clinical outcomes (sudden death, aborted sudden death, ventricular tachycardia, ventricular fibrillation, and appropriate implantable cardioverter-defibrillator [ICD] therapy, including antitachycardia pacing). A meta-analysis was performed to determine pooled odds ratios (ORs) for these arrhythmic events. ResultsNineteen studies that evaluated 2,850 patients with 423 arrhythmic events over a mean/median follow-up of 2.8 years were identified. The composite arrhythmic endpoint was reached in 23.9% of patients with a positive LGE test (annualized event rate of 8.6%) versus 4.9% of patients with a negative LGE test (annualized event rate of 1.7%; p < 0.0001). LGE correlated with arrhythmic events in the different patient groups. In the overall population, the pooled OR was 5.62 (95% confidence interval [CI]: 4.20 to 7.51), with no significant differences between ICM and NICM patients. In a subgroup of 11 studies (1,178 patients) with mean ejection fraction (EF) ≤30%, the pooled OR for the arrhythmic events increased to 9.56 (95% CI: 5.63 to 16.23), with a negative likelihood ratio of 0.13 (95% CI: 0.06 to 0.30). ConclusionsLGE is a powerful predictor of ventricular arrhythmic risk in patients with ventricular dysfunction, irrespective of ICM and NICM etiology. The prognostic power of LGE is particularly strong in patients with severely depressed EF, which suggests its potential to improve patient selection for ICD implantation.

Mid-wall fibrosis on delayed enhancement CMR - a marker for adverse left ventricular chamber remodeling independent of cardiomyopathic etiology

Background Mid-wall fibrosis (MWF) is a hallmark of non-ischemic cardiomyopathy (NICM) that confers increased risk for sudden cardiac death and mortality. The relationship between MWF and left ventricular (LV) remodeling is unknown. Methods The population comprised patients with advanced systolic dysfunction (LVEF ≤ 40%) undergoing CMR (1.5T, General Electric Signa). Ischemic vs. NICM etiology was classified in accordance with established convention based on obstructive CAD on invasive angiography. Delayed enhancement CMR (IR-GRE acquired 10-30 minutes post gadolinium [0.2 mmol/kg]) was used to identify MWF, defined as hyperenhancement confined to the mid-myocardial or epicardial aspect of the interventricular septum. LV mass and chamber volume were quantified by planimetry of contiguous SSFP cine-CMR short axis slices, with ejection fraction (EF) calculated as the proportional difference between end-diastolic (EDV) and end-systolic (ESV) volumes. Results 523 patients (61 ± 14 yo, 72% M, 66% ischemic CM) were studied: MWF was present in 16%, and was 6-fold more common in patients with angiographically classified NICM (37% vs. 6%; p < 0.001). Regarding LV remodeling, MWF was associated with higher EDV (134 ± 39 ml vs. 114 ± 34 ml; p < 0.001) and LV mass (102 ± 24 vs. 96 ± 28 gm; p < 0.001) and lower LVEF (26 ± 8% vs. 30 ± 8%; p ≤ 0.05). MWF was nearly 3-fold more common among patients in the highest tertile of EDV vs. the remainder of the population (29% vs. 10%; p < 0.001). Multivariate regression analysis was performed to further assess markers for MWF: Restricted to imaging indices, results (Table 1A) demonstrated EF and EDV to be independently associated with MWF (OR = 1.46, CI 1.03-2.10; p < 0.05, OR = 1.13, CI 1.04-1.20; p < 0.05, respectively) after controlling for mass (OR = 0.95, CI 0.85-1.00; p = 0.29). Regarding clinical variables, results (Table 1B) confirmed a strong association with NICM (OR = 8.4, CI 4.78-14.72; p < 0.001), independent of other clinical indices. A combined model incorporating both clinical and imaging variables demonstrated both NICM and LV volume to be independently associated with MWF even after controlling for EF (Table 1C). Overall strength of the combined clinical/imaging (c 2 = 91.2; p < 0.001) model for MWF was higher than that of isolated clinical (c 2 = 76.7; p < 0.001) and imaging (c 2 = 26.0; p < 0.001) models.

Reduction in Exhaled Acetone Tracks with Weight Loss Following Diuretic Therapy in Acute Decompensated Heart Failure

human heart failure (HF). Methods: Thus, we measured serum NRG using ELISA in patients with HF, either due to ischemic (ISCH) or non-ischemic cardiomyopathy (NICM), and carefully characterized their clinical status to assess physiologic NRG response. Results: Serum NRG in 156 patients (mean age 60 6 13 years, 72% male, with mean LV ejection fraction (LVEF) of 30 6 14) who have symptomatic HF, either ISCH (n 5 68) or NICM (n 5 88), were measured. The entire cohort included 57% with hypertension, 32% diabetic and 38% with obesity while a high percentage were on optimal medical therapy including ACE inhibitor (82%), betablockers (91%) and diuretics (75%). There were no significant differences between groups regarding risk factors or percent on optimal medical therapy. Table 1 summarizes the NRG values and degree of HF between ISCH and NICM patients. Conclusion: Serum NRG values appear reduced in HF patients with ISCH compared to NICM etiology. This may reflect reduced production of this endothelial cell derived factor in the presence of advanced atherosclerosis.

Characteristics of Responders to Cardiac Resynchronization Therapy: The Impact of Echocardiographic Left Ventricular Volume

One-third of patients who receive cardiac resynchronization therapy (CRT) are classified as nonresponders. Characteristics of responders to CRT have been studied in multiple clinical trials. Independent predictors of CRT response may be identified by studying a series of patients in routine clinical practice. One hundred twenty-five patients were examined retrospectively from a multidisciplinary CRT clinic program. Echocardiographic CRT response was defined as a decrease in left ventricular (LV) end-systolic volume of ≥15% and/or absolute increase of 5% in LV ejection fraction at the 6-month visit. There were 81 responders and 44 nonresponders. By univariate analyses, female sex, nonischemic cardiomyopathy etiology, baseline QRS duration, the presence of left bundle branch block (LBBB), and left ventricular end-diastolic volume (LVEDV) index predicted CRT response. However, multivariate analysis demonstrated that only QRS duration, LBBB, and LVEDV index were independent predictors (QRS width, odds ratio [OR]: 1.027, 95% confidence interval [CI]: 1.004-1.050, P = 0.023; LBBB, OR: 3.568, 95% CI: 1.284-9.910, P = 0.015; LVEDV index, OR: 0.970, 95% CI: 0.953-0.987, P = 0.001). Although female sex and nonischemic etiology were associated with an improved CRT response on univariate analyses, after adjusting for LV volumes they were not independent predictors. QRS width, LBBB, and LVEDV index are independent predictors for echocardiographic CRT response. Previously reported differences in CRT response for sex and cardiomyopathy etiology are associated with differences in baseline LV volumes in our clinical practice.

Die Rolle der Kardio-MRT bei Diagnose und Prognosebeurteilung der Herzinsuffizienz

Cardiovascular magnetic resonance (CMR) imaging is a tomographic technique, which allows three-dimensional slice orientation without limitations from acoustic windows inherent to echocardiography. Further advantages of CMR are its high temporal and spatial resolution, its excellent soft tissue resolution and its high blood-to-tissue contrast. Cardiovascular magnetic resonance is currently the only imaging technique, which provides a comprehensive study of both structure and function of the heart as well as myocardial perfusion and viability. Moreover, post-processing of CMR images does not require any geometric assumptions as in echocardiography to determine ventricular dimensions. This is particularly important when evaluating ventricles of patients with chronic heart failure with severely altered morphology that may have regional variations in wall thickness and contractility at least in ischemic cardiomyopathy. The highly reproducible results of CMR imaging have turned this technique into a reference standard for the non-invasive assessment of ventricular dimensions, mass and function. In cases with indeterminate results of clinical, electrocardiographic and particularly echocardiographic findings CMR should be used early in the process of diagnosis of patients with heart failure. Not only can altered structure and degree of ventricular and valvular dysfunctions be accurately assessed but also regional perfusion deficits and/or myocardial scars are easily detected. For therapeutic and prognostic reasons a simple differentiation between ischemic and non-ischemic cardiomyopathy should be achieved as the first diagnostic step. In addition, the type and localization of the late gadolinium enhancement (LGE) phenomenon may aid in non-invasively differentiating the etiology of non-ischemic cardiomyopathy. CMR may also improve the assessment and extent of interventricular and intraventricular dyssynchrony in patients to be selected for cardiac resynchronization therapy (CRT). Lastly, the LGE phenomenon may provide independent prognostic information in patients with a CRT system implanted, as well as in patients with ischemic and non-ischemic cardiomyopathy. Thus, CMR imaging should be implemented early in the diagnostic process of patients with heart failure to significantly improve the speed and accuracy of diagnostic procedures, to control the effect of therapeutic measures, and to select patients with a limited prognosis by assessing the degree of ventricular dysfunction and the extent of myocardial scarring.