Prognosis Of Dilated Cardiomyopathy Research Articles

The Prognostic Value of Serum Calcium Levels in Elderly Dilated Cardiomyopathy Patients.

It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan-Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Serum calcium level could be served as a simple and affordable tool to evaluate patients' prognosis in DCM.

A pilot study of S100A4, S100A8/A9, and S100A12 in dilated cardiomyopathy: novel biomarkers for diagnosis or prognosis?

Circulating biomarkers can provide important information for the diagnosis and prognosis of dilated cardiomyopathy (DCM). We explored novel biomarkers for the diagnosis and prognosis of DCM to improve clinical decision-making. A total of 238 DCM patients and 65 control were consecutively enrolled at Zhongshan Hospital between January 2017 and January 2019. In the screening set, four DCM patients and four controls underwent measurements of serum proteomic analysis. Seventy-six differentially expressed circulating proteins were screened by data-independent acquisition proteomics, and three of these proteins (S100A4, S100A8/A9, and S100A12) were validated by multiple-reaction monitoring-mass spectrometry. In the validation set, subsequently, a total of 234 DCM patients and 61 control subjects were evaluated by enzyme-linked immunosorbent assay. Circulating S100A4, S100A8/A9, and S100A12 were significantly increased in DCM patients (P<0.001). These three proteins were significant positively correlated with other parameters, such as Lg (NT-proBNP), IL-1β, TGF-β, CRP, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter, whereas they were negatively correlated with left ventricular ejection fraction, respectively (P<0.05). The receiver operator characteristic curve showed the combination of S100A4, S100A8/A9, and S100A12 [area under curve (AUC) 0.88, 95% confidence interval (CI) 0.84-0.93] was better than single S100A4 (AUC 0.74, 95% CI 0.68-0.81), S100A8/A9 (AUC 0.82, 95% CI 0.77-0.88), or S100A12 (AUC 0.80, 95% CI 0.72-0.88) in the diagnosis of DCM (P<0.01). After a median follow-up period of 33.5months, 110 patients (47.01%) experienced major adverse cardiac events (MACEs), including 46 who had cardiac deaths and 64 who had heart failure rehospitalizations. Kaplan-Meier analysis indicated that the DCM patients with ≥75th percentile level of S100A4 had a significantly higher incidence of MACEs than those with <75th percentile level of S100A4 (61.40% vs. 42.37%, P<0.05). There were no significant differences of MACE rate among DCM patients with different concentrations of S100A8/A9 and S100A12 (P>0.05). Cox proportional hazards regression analysis revealed that S100A4 [≥75th percentile vs. <75th percentile: hazard ratio (HR) 1.65; 95% CI 1.11-2.45] remained significant independent predictors for MACEs (P<0.05); however, S100A8/A9 and S100A12 were not independent factors for predicting MACE (P≥0.05). S100A4, S100A8/A9, and S100A12 may be additional diagnostic tools for human DCM recognition, and the combination of these three indicators helped to improve the accuracy of a single index to diagnose DCM. Additionally, S100A4 was identified as a significant predictor of prognosis in patients with DCM.

Investigating the role of NPR1 in dilated cardiomyopathy and its potential as a therapeutic target for glucocorticoid therapy.

Background: Dilated cardiomyopathy (DCM), a specific form of cardiomyopathy, frequently presents clinically with either left ventricular or biventricular enlargement, often leading to progressive heart failure. In recent years, the application of bioinformatics technology to scrutinize the onset, progression, and prognosis of DCM has emerged as a fervent area of interest among scholars globally. Methods: In this study, core genes closely related to DCM were identified through bioinformatics analysis, including weighted gene co expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) and so on. The correlation was verified through experiments on DCM patients, DCM rat models, and core gene knockout mice. Subsequently, the effects of glucocorticoids on DCM and the regulation of core genes were observed. Result: In the present study, natriuretic peptide receptor 1 (NPR1) was identified as a core gene associated with DCM through WGCNA and ssGSEA. Significant impairment of cardiac and renal function was observed in both DCM patients and rats, concomitant with a notable reduction in NPR1 expression. NPR1 KO mice displayed symptomatic manifestations of DCM, underscoring the pivotal role of NPR1 in its pathogenesis. Notably, glucocorticoid treatment led to substantial improvements in cardiac and renal function, accompanied by an upregulation of NPR1 expression. Discussion: These findings highlight the critical involvement of NPR1 in the pathophysiology of DCM and its potential as a key target for glucocorticoid-based DCM therapy. The study provides a robust theoretical and experimental foundation for further investigations into DCM etiology and therapeutic strategies.

Biomarkers of Collagen Metabolism Are Associated with Left Ventricular Function and Prognosis in Dilated Cardiomyopathy: A Multi-Modal Study.

Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM. DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5-8). In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = -0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = -0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002-1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004). The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients.

CMR-derived left ventricular intraventricular pressure gradients identify different patterns associated with prognosis in dilated cardiomyopathy.

Left ventricular (LV) blood flow is determined by intraventricular pressure gradients (IVPG). Changes in blood flow initiate remodelling and precede functional decline. Novel cardiac magnetic resonance (CMR) post-processing LV-IVPG analysis might provide a sensitive marker of LV function in dilated cardiomyopathy (DCM). Therefore, the aim of our study was to evaluate LV-IVPG patterns and their prognostic value in DCM. LV-IVPGs between apex and base were measured on standard CMR cine images in DCM patients (n = 447) from the Maastricht Cardiomyopathy registry. Major adverse cardiovascular events, including heart failure hospitalisations, life-threatening arrhythmias, and sudden/cardiac death, occurred in 66 DCM patients (15%). A temporary LV-IVPG reversal during systolic-diastolic transition, leading to a prolonged transition period or slower filling, was present in 168 patients (38%). In 14%, this led to a reversal of blood flow, which predicted outcome corrected for univariable predictors [hazard ratio (HR) = 2.57, 95% confidence interval (1.01-6.51), P = 0.047]. In patients without pressure reversal (n = 279), impaired overall LV-IVPG [HR = 0.91 (0.83-0.99), P = 0.033], systolic ejection force [HR = 0.91 (0.86-0.96), P < 0.001], and E-wave decelerative force [HR = 0.83 (0.73-0.94), P = 0.003] predicted outcome, independent of known predictors (age, sex, New York Heart Association class ≥ 3, LV ejection fraction, late gadolinium enhancement, LV-longitudinal strain, left atrium (LA) volume-index, and LA-conduit strain). Pressure reversal during systolic-diastolic transition was observed in one-third of DCM patients, and reversal of blood flow direction predicted worse outcome. In the absence of pressure reversal, lower systolic ejection force, E-wave decelerative force (end of passive LV filling), and overall LV-IVPG are powerful predictors of outcome, independent of clinical and imaging parameters.

The prognostic value of the left atrial strain rate determined using cardiovascular magnetic resonance feature tracking imaging in patients with severe idiopathic dilated cardiomyopathy.

Left atrial strain rate (LASR) is rarely used as an indicator of cardiovascular disorder prognosis in dilated cardiomyopathy (DCM). In the present study, we aimed to explore the prognostic value of the LASR in patients with severe idiopathic DCM [left ventricle ejection fraction (LVEF) <35%] using cardiac magnetic resonance feature tracking (CMR-FT). A retrospective cohort study was performed. At the time of enrollment, patients who underwent cardiovascular magnetic resonance (CMR) imaging were selected for the study. Left atrium (LA) strain rate was measured in patients with severe idiopathic DCM from four-chamber and two-chamber views using a 3.0-T CMR scanner. The study endpoint was defined as a combination of all-cause death, implantable cardioverter-defibrillator (ICD), hospitalization due to cardiac failure, and heart transplantation. Cox model analyses were used to assess the statistical significance of the risk factors. Fifty-eight patients with a confirmed diagnosis of severe idiopathic DCM were ultimately included in the analysis [mean age of 46 years; 41 (73%) men]. The median follow-up was 43 months (13-72 months). Adverse cardiovascular events occurred in 29 patients: all-cause death occurred in 15 participants (25.8%), ICD was performed in 5 participants (8.6%), heart failure hospitalization occurred in 8 participants (13.8%), and 1 participant (1.7%) underwent heart transplantation. From univariate analysis, the left atrium reservoir strain rate (LASRs) [HR 0.12; 95% CI (0.02, 0.55), P=0.007] and the left atrium booster pump strain rate (LASRa) [HR 3.21; 95% CI (1.08, 9.58), P=0.036] significantly predicted the association with cardiovascular events. In model 1 after adjusting for basic cardiovascular risk factors, including age, hypertension, diabetes mellitus, and N-terminal pro-brain natriuretic peptide (NT-proBNP), the LASRs [HR 0.12, 95% CI (0.02, 0.58), P=0.009] was assessed. The mitral valve regurgitation, LA maximum volume index, and LA diastatic volume index were added in model 2 based on model 1. LASRs [HR 0.13, 95% CI (0.02. 0.82) P=0.030] was the independent prediction factor after adjustment for model 1 and model 2. The LASRs had a good prognostic value with an area under the curve of receiver operating characteristic of 0.697 (0.617, 0.777) at 1 year, 0.716 (0.643, 0.788) at 3 years, 0.716 (0.651, 0.798) at 5 years and 0.703 (0.597, 0.809) at 7 years. LA reservoir strain rate and active strain rate were powerful prognostic markers. The LASRs by MRI-FT provided independent prognostic value in patients with severe idiopathic DCM.

Evaluation of extracellular volume by computed tomography is useful for prediction of prognosis in dilated cardiomyopathy.

Cardiac computed tomography (CT) is useful for the screening of coronary artery stenosis, and extracellular volume fraction (ECV) analysis by CT using new dedicated software is now available. Here, we evaluated the utility of ECV analysis using cardiac CT to predict patient prognosis in cases with dilated cardiomyopathy (DCM). We analyzed 70 cases with DCM and cardiac computed tomography (CT) with available late-phase images. We evaluated the ECV of the left ventricular myocardium (LVM) using commercially available software (Ziostation 2, Ziosoft Inc, Japan). ECV on LVM was 33.96 ± 5.04%. Major adverse cardiac events (MACE) occurred in 21 cases (30%). ECV of the LVM on CT, endo-systolic volume, and rate of significant valvular disease were significantly higher in cases with MACE than in those without (37.16 ± 5.91% vs. 32.59 ± 3.95%, 194 ± 109 vs. 138 ± 78ml and 57% vs. 20%, all P values < 0.05). LVEF was significantly lower in cases with MACE than in those without (23 ± 8 vs. 31 ± 11%, P = 0.0024). The best cut-off value of ECV on LVM for prediction of MACE was 32.26% based on receiver operating characteristics analysis. Cases with ECV ≥ 32.26% had significantly higher MACE based on Kaplan-Meier analysis (P = 0.0032). Only ECV on LVM was an independent predictor of MACE based on a multivariate Cox proportional hazards model (P = 0.0354). Evaluation of ECV on LVM by CT is useful for predicting MACE in patients with DCM.

Albumin-Bilirubin Score to Predict Outcomes in Patients with Idiopathic Dilated Cardiomyopathy.

ResumoFundamento:A disfunção hepática é uma variável postulada de prognóstico desfavorável na cardiomiopatia dilatada (CMD).Objetivo:Este estudo teve como objetivo investigar o valor prognóstico do escore albumina-bilirrubina (ALBI), um modelo relativamente novo para a avaliação da função hepática, em pacientes com CMD idiopática.Métodos:Um total de 1.025 pacientes com CMD idiopática foram incluídos retrospectivamente e divididos em três grupos com base nos escores de ALBI: grau 1 (≤ −2,60, n = 113), grau 2 (−2,60 a −1,39, n = 835) e grau 3 (> −1,39, n = 77). Foi analisada a associação do escore ALBI com eventos clínicos adversos maiores (ECAM) intra-hospitalares e mortalidade a longo prazo. Valor de p inferior a 0,05 foi considerado estatisticamente significativo.Resultados:A taxa de ECAM intra-hospitalares foi significativamente maior nos pacientes com grau 3 (2,7% versus 7,1% versus 24,7%, p < 0,001). A análise multivariada mostrou que o escore ALBI foi um preditor independente para ECAM intra-hospitalares (odds ratio ajustada = 2,80, IC 95%: 1,63 – 4,80, p < 0,001). Após seguimento mediano de 27 meses, 146 (14,2%) pacientes morreram. A curva de Kaplan-Meier indicou que a taxa cumulativa de sobrevida a longo prazo foi significativamente menor em pacientes com grau mais alto de ALBI (log-rank = 45,50, p < 0,001). O escore ALBI foi independentemente associado à mortalidade a longo prazo (hazard ratio ajustada = 2,84, IC 95%: 1,95 – 4,13, p < 0,001).Conclusão:O escore ALBI, como modelo de risco simples, pode ser considerado uma ferramenta de estratificação de risco para pacientes com CMD idiopática.

Analysis of SIRT4 gene single-nucleotide polymorphisms in a Han Chinese population with dilated cardiomyopathy.

Aim: We aimed to investigate the association of SIRT4 gene polymorphisms with the susceptibility and prognosis of dilated cardiomyopathy (DCM) in a Chinese population. Materials & methods: A total of 369 controls and 373 DCM patients were enrolled. Three tag single-nucleotide polymorphisms (rs2261612, rs2522138 and rs16950058) on SIRT4 were evaluated. Results: G carriers of rs2261612 were associated with the susceptibility of DCM in codominant, dominantand overdominant genetic models (all p<0.01). Furthermore, the AG/GG and AG genotype of rs2261612 in dominant and overdominant models correlated with poor prognosis of DCM, independent of left ventricular ejection fraction and cardiac resynchronization therapy (p<0.001). Conclusion:SIRT4 polymorphisms were associated with the susceptibility and prognosis of DCM in a Chinese population.

Thyroid Hormones-An Underestimated Player in Dilated Cardiomyopathy?

Dilated cardiomyopathy (DCM) is the most prevalent cardiomyopathy, typified by left ventricular dilation and systolic dysfunction. Many patients with DCM have altered thyroid status, especially lower levels of free triiodothyronine (T3) and elevated levels of thyroid-stimulating hormone. Moreover, growing evidence indicates that even subtle changes in thyroid status (especially low T3) are linked with a worse long-term prognosis and a higher risk of mortality. Notably, recent discoveries have shown that not only local myocardial thyroid hormones (THs) bioavailability could be diminished due to impaired expression of the activating deiodinase, but virtually all genes involved in TH biosynthesis are also expressed in the myocardium of DCM patients. Importantly, some studies have suggested beneficial effects of TH therapy in patients suffering from DCM. Our aim was to discuss new insights into the association between TH status and prognosis in DCM, abnormal expression of genes involved in the myocardial synthesis of TH in DCM, and the potential for TH use in the future treatment of DCM.

A plasmatic microrna fingerprint for reduced ejection fraction in dilated cardiomyopathy

Background and Aims: The left ventricular ejection fraction(LVEF) is key to prognosis in dilated cardiomyopathy(DCM). Circulating microRNAs have emerged as reliable biomarkers for cardiovascular diseases. Improved tools for better determination of DCM-EF categorization, to identify high-risk patients are needed. Our aim is to assess microRNAs a useful marker to categorize DCM patients based on their EF.

Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy

The left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify high-risk patients. Thus, we investigated whether microRNA profiles can categorize DCM patients based on their EF. 179-differentially expressed circulating microRNAs were screened in two groups: (1) non-idiopathic DCM; (2) idiopathic DCM. Then, 26 microRNAs were identified and validated in the plasma of ischemic-DCM (n = 60), idiopathic-DCM (n = 55) and healthy individuals (n = 44). We identified fourteen microRNAs associated with echocardiographic variables that differentiated idiopathic DCM according to the EF degree. A predictive model of a three-microRNA (miR-130b-3p, miR-150-5p and miR-210-3p) combined with clinical variables (left bundle branch block, left ventricle end-systolic dimension, lower systolic blood pressure and smoking habit) was obtained for idiopathic DCM with a severely reduced-EF. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. Bioinformatics analysis revealed that miR-150-5p and miR-210-3p target genes might interact with each other with a high connectivity degree. In conclusion, our results revealed a three-microRNA signature combined with clinical variables that highly discriminate idiopathic DCM categorization. This is a potential novel prognostic biomarker with high clinical value.

Prognostic value of free triiodothyronine in patients with dilated cardiomyopathy.

BackgroundThe association between free triiodothyronine (FT3) and long-term prognosis in dilated cardiomyopathy (DCM) patients has not been evaluated. The purpose of this study was to determine whether the level of FT3 could provide prognostic value in patients with DCM.MethodsData of consecutive patients diagnosed with DCM were collected from October 2009 to December 2014. FT3 was measured by fluoroimmunoassay. Other biochemical markers, such as free thyroxin (FT4), thyroid-stimulating hormone, red blood cell, hemoglobin, blood urea nitrogen, and serum creatinine, were tested at the same time. Follow-up was performed every 3 months. The primary endpoint was all-cause mortality. Pearson analysis was used to evaluate the correlation of FT3 and other lab metrics with DCM patients’ prognosis. The association of long-term mortality in DCM and FT3 was compared using Cox hazards model.ResultsData of 176 patients diagnosed with DCM were collected. Of them, 24 patients missed FT3 values and six patients were lost to follow-up. Altogether, data of 146 patients were analyzed. During the median follow-up time of 79.9 (53.5–159.6) months, nine patients lost, 61 patients died (non-survival group), and 85 patients survived (survival group). FT3 was significantly lower in non-survival group than that in survival group (3.65 ± 0.83 pmol/L vs. 4.36 ± 1.91 pmol/L; P = 0.003). FT3 also showed a significantly positive correlation with red blood cell and hemoglobin, negatively correlated with age, blood urea nitrogen and serum creatinine (P < 0.05), respectively. Patients in the group of lower FT3 levels (FT3 ≤3.49 pmol/L) suffered from a higher risk of all-cause mortality (P for log-rank = 0.001). In multivariate Cox regression analysis, FT3 level was significantly associated with all-cause mortality (hazard ratio: 0.70, 95% confidence interval 0.52–0.95, P for trend = 0.021).ConclusionLow levels of FT3 were associated with increased all-cause mortality in patients with DCM.

Late gadolinium enhancement on cardiac magnetic resonance combined with 123I- metaiodobenzylguanidine scintigraphy strongly predicts long-term clinical outcome in patients with dilated cardiomyopathy.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is limited in its ability to detect diffuse interstitial fibrosis, which is commonly found in idiopathic dilated cardiomyopathy (DCM). On the other hand, Washout rate (WR) by cardiac 123I- metaiodobenzylguanidine (123I-MIBG) scintigraphy which evaluates cardiac sympathetic nervous function, is a useful tool for predicting the prognosis in DCM. We investigated the predictive value of the combination of two different types of examinations, LGE on CMR and WR by 123I-MIBG scintigraphy for outcomes in DCM compared with LGE alone. One-hundred forty-eight DCM patients underwent CMR and 123I-MIBG scintigraphy. Patients were divided into 4 groups according to the presence or absence of LGE and WR cut-off value of 45% for predicting prognosis based on receiver operating characteristic curve analysis. Cardiac deaths, re-hospitalization for heart failure, implantation of a left ventricular assist device, and life-threatening ventricular arrhythmias were defined as clinical events. Forty-two DCM patients reached the clinical events during the median follow-up for 9.1 years (interquartile range, 8.0–9.2 years).Multivariable Cox regression analysis identified WR≥45%+LGE positive group as an independent predictor of cardiac events (HR 3.18, 95%CI 1.36–7.45, p = 0.008). Notably, there was no significance in the cardiac event-free survival rate between the WR<45%+LGE positive and WR≥45%+LGE negative groups (p = 0.89). The combination of WR by 123I-MIBG scintigraphy and LGE on CMR, which evaluate different type of cardiac deterioration, serves as a stronger predictor of long-term outcomes in DCM patients than LGE alone.

Association Between AXIN1 Gene Polymorphisms and Dilated Cardiomyopathy in a Chinese Han Population.

Dilated cardiomyopathy (DCM) is a common type of cardiomyopathy. The pathogenesis of DCM remains unclear and involves varied genes. AXIN1 is a crucial gene in regulating various functions in cells, it encodes protein Axin1, which regulates the assembly and disassembly of β-catenin destruction complex. In addition, Wnt/β-catenin signaling pathway plays an important role in cardiogenesis. We aimed to detect whether AXIN1 polymorphisms contribute to the susceptibility and prognosis of DCM in a Chinese Han population. A total of 340 DCM patients and 430 controls were enrolled, and patients who had complete contact information were followed up for a median period of 49 months. Polymerase chain reaction-restriction fragment length polymorphism was carried out to genotype the two AXIN1 tag single nucleotide polymorphisms (SNPs) (rs12921862 and rs1805105). All data were analyzed using the statistical software package, SPSS 21.0. The frequencies of allele A in rs12921862 and allele C in rs1805015 were increased in DCM patients compared with healthy controls (p < 0.001). Genotypic frequencies of rs12921862 and rs1805105 were associated with the susceptibility of DCM in codominant, dominant, and overdominant models (p < 0.01). AA/AC and AC genotypes of rs12921862 in the dominant and the overdominant genetic models also presented a correlation with poor prognosis of DCM in both univariate (p < 0.01) and multivariate analyses (p < 0.01) after adjusting for age, gender, left ventricular (LV) end-diastolic diameter, and LV ejection fraction. Our results suggest that AXIN1 polymorphisms are associated with the susceptibility and prognosis of DCM in a Chinese Han population.

Outcome in Dilated Cardiomyopathy Related to the Extent, Location, and Pattern of Late Gadolinium Enhancement

ObjectivesThis study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort. BackgroundThe relationship between LGE and prognosis in DCM is incompletely understood. MethodsThe authors examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM. ResultsOf 874 patients (588 men, median age 52 years) followed for a median of 4.9 years, 300 (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59 (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and 2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to 5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD endpoint. There was a marked nonlinear relationship between LGE extent and outcome such that even small amounts of LGE predicted a substantial increase in risk. The presence of septal LGE was associated with increased mortality, but SCD was most associated with the combined presence of septal and free-wall LGE. Predictive models using LGE presence and location were superior to models based on LGE extent or pattern. ConclusionsIn DCM, the presence of septal LGE is associated with a large increase in the risk of death and SCD events, even when the extent is small. SCD risk is greatest with concomitant septal and free-wall LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is limited.

HUMAN EPIDIDYMIS PROTEIN 4 IS A NOVEL FIBROSIS MARKER TO PREDICT PATHOLOGICAL CARDIAC REMODELING AND ADVERSE OUTCOMES IN PATIENTS WITH DILATED CARDIOMYOPATHY

The prognosis of dilated cardiomyopathy (DCM) remains unfavorable because of progressive depression of cardiac function. Cardiac interstitial fibrosis plays a crucial role in the pathophysiology of DCM. Human Epididymis Protein 4 (HE-4), novel fibrosis marker, is specifically expressed in activated

Usefulness of Urinary N-Terminal Fragment of Titin to Predict Mortality in Dilated Cardiomyopathy

Titin is associated with myocardial stiffness and hypertrophy, and mutations in its gene have been identified in cardiac myopathies such as dilated cardiomyopathy (DC). It has recently been reported that in damaged muscle, the N-terminal fragment of titin (Titin-N) is cleaved by calpain-3, and urinary Titin-N (U-TN) could be a marker of sarcomere damage. We aimed to investigate the impact of U-TN on prognosis of DC. We measured urinary levels of Titin-N/creatinine ratio (U-TN/Cr; pmol/mg/dl) in 102 patients with DC, and followed up all the patients (mean 1,167 days). The patients were divided into 3 groups based on the U-TN/Cr: first (U-TN/Cr <3.35, n = 34), second (3.35 ≤ U-TN/Cr <7.26, n = 34), and third (7.26 ≤ U-TN/Cr, n = 34) tertiles. In the Kaplan-Meier analysis, cardiac and all-cause mortality progressively increased from the first to the second and third groups (p <0.05, respectively). In the Cox proportional hazard analyses, U-TN/Cr was a predictor of cardiac and all-cause mortality in patients with DC (p <0.05, respectively). U-TN, a possible marker of sarcomere damage, can identify high-risk patients with DC.

Evolving concepts in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few co-morbidities. The prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the red-flag integrated approach to the disease, early diagnosis through systematic familial screening, and the concept of DCM as a dynamic disease requiring constant optimization of medical and non-pharmacological evidence-based treatments. However, some important issues in clinical management remain unresolved, including the role of cardiac magnetic resonance for diagnosis and risk categorization and the interaction between genotype and clinical phenotype, and arrhythmic risk stratification. This review offers a comprehensive survey of these and other emerging issues in the clinical management of DCM, providing where possible practical recommendations.

Influence of LGALS3 gene polymorphisms on susceptibility and prognosis of dilated cardiomyopathy in a Northern Han Chinese population

BackgroundGalectin-3 plays an important role in modulating cardiac inflammation and fibrosis. It also takes part in the pathways underlying cardiac remodeling. Therefore, LGALS3 gene, encoding galectin-3 protein, is a promising candidate for the genetic study of dilated cardiomyopathy (DCM). To date, there has been no research evaluating the association between LGALS3 gene polymorphisms and the susceptibility and prognosis of DCM. Methods and ResultsGenotyping of 4 single nucleotide polymorphisms (SNPs) in the LGALS3 gene, which were reported to be functional in the literature, was performed in 279 unrelated clinically diagnosed DCM patients and 363 apparently healthy controls from Northern Han Chinese population using iPLEX SNP Genotyping analysis on a Sequenom MassARRAY System. The frequency of G allelic polymorphism of rs1009977 and the C allelic polymorphism of rs4652 were lower in DCM patients (OR=0.77, 95% CI [0.60–0.99], P=0.045; OR=0.79, 95% CI [0.63–0.99], P=0.042, respectively). The minor variants of rs1009977 and rs4652 were associated with low susceptibility of DCM under additive genetic models (P=0.045 and P=0.040, respectively). The AA genotype of both rs2274273 and rs4644 was associated with lower left ventricular ejection fraction (recessive model, P=0.018 for both; additive model, P=0.039 for both). The G variant of rs1009977 was related with lower serum galectin-3 level in DCM patients under three genetic models (additive model, P=0.020, dominant model, P=0.020, recessive model, P=0.037). The A variant of both rs2274273 and rs4644 was associated with lower level of galectin-3 in DCM patients under additive model (P=0.032 for both) and dominant model (P=0.012 for both). None of the 4 SNPs was associated with the cardiovascular or all-cause death rate of DCM. In Conclusion, LGALS3 gene polymorphisms might be associated with the susceptibility of DCM in a Northern Han Chinese population.