Idiopathic Dilated Cardiomyopathy Patients Research Articles

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

Cardiogenic shock in idiopathic dilated cardiomyopathy patients: Red flag for myocardial decline

Cardiogenic shock in idiopathic dilated cardiomyopathy patients: Red flag for myocardial decline

Cardiogenic Shock in Idiopathic Dilated Cardiomyopathy Patients: Red Flag for Myocardial Decline

Idiopathic dilated cardiomyopathy (IDCM) is one of the most common forms of nonischemic cardiomyopathy worldwide, possibly leading to cardiogenic shock (CS). Despite this heavy burden, the outcomes of CS in IDCM are poorly reported. Based on a large registry of unselected CS, our aim was to shed light on the 1-year outcomes after CS in patients with and without IDCM. FRENSHOCK was a prospective registry including 772 patients with CS from 49 centers. The 1-year outcomes (rehospitalizations, mortality, heart transplantation [HTx], ventricular assist devices [VAD]) were analyzed and adjusted on independent predictive factors. Within 772 CS included, 78 occurred in IDCM (10.1%). Patients with IDCM had more frequent history of chronic kidney failure and implantable cardioverter-defibrillator implantation. No difference was found in 1-month all-cause mortality between groups (28.2 vs 25.8%for IDCM and others, respectively; adjusted hazard ratio 1.14 [0.73 to 1.77], p=0.57). Patients without IDCM were more frequently treated with noninvasive ventilation and intra-aortic balloon pump. At 1 year, IDCM led to higher rates of death or cardiovascular rehospitalizations (adjusted odds ratio 4.77 [95% confidence interval 1.13 to 20.1], p=0.03) and higher rates of HTx or VAD for patients aged <65 years (adjusted odds ratio 2.68 [1.21 to 5.91], p=0.02). In conclusion, CS in IDCM is a very common scenario and is associated with a higher rate of 1-year death or cardiovascular rehospitalizations and a more frequent recourse to HTx or VAD for patients aged <65 years, encouraging the consideration of it as a red flag for myocardial decline and urging for a closer follow-up and earlier evaluation for advanced heart failure therapies.

Association between low-density lipoprotein cholesterol level and all-cause mortality in idiopathic dilated cardiomyopathy patients: a single-institutional study

Aims To determine the association between all-cause mortality and low-density lipoprotein cholesterol (LDL-C) in patients with idiopathic cardiomyopathy (iDCM). Background LDL-C had long been considered as a dangerous predictor of cardiovascular diseases; however, the correlation between them was not fully clarified. Methods A total of 1058 patients who met the World Health Organization criteria for iDCM in West China Hospital (2009–2016) were enrolled in this retrospective study. Baseline demographic characteristics and correlations between variables were calculated and analyzed, and potential predictors were explored using univariate and multivariate regressions. Cox proportional hazards models were used to determine correlation on a continuous scale. Results LDL-C is an independent prognostic factor and higher LDL-C levels are associated with better prognosis in iDCM patients according to cox regression analysis. Compared with individuals which LDL > 2.28 mmol/L (75th–100th percentile), the multivariable-adjusted hazard ratio for all-cause mortality was 1.52 (95%CI: 1.03–2.26) in patients with LDL-C < 1.78 mmol/L (0–25th percentile). In patients with New York Heart Association function III and IV, LDL-C levels have a hazard ratio of 0.83 (confidence interval 0.73–0.95). Conclusions In patients with iDCM, lower LDL-C level was associated with an increased risk of all-cause mortality. The correlation between mortality and LDL-C level was stronger in patients with worse heart function. LDL-C levels have a potential predictive value in iDCM patients.

CCND1 Overexpression in Idiopathic Dilated Cardiomyopathy: A Promising Biomarker?

Cardiomyopathy, a disorder of electrical or heart muscle function, represents a type of cardiac muscle failure and culminates in severe heart conditions. The prevalence of dilated cardiomyopathy (DCM) is higher than that of other types (hypertrophic cardiomyopathy and restrictive cardiomyopathy) and causes many deaths. Idiopathic dilated cardiomyopathy (IDCM) is a type of DCM with an unknown underlying cause. This study aims to analyze the gene network of IDCM patients to identify disease biomarkers. Data were first extracted from the Gene Expression Omnibus (GEO) dataset and normalized based on the RMA algorithm (Bioconductor package), and differentially expressed genes were identified. The gene network was mapped on the STRING website, and the data were transferred to Cytoscape software to determine the top 100 genes. In the following, several genes, including VEGFA, IGF1, APP, STAT1, CCND1, MYH10, and MYH11, were selected for clinical studies. Peripheral blood samples were taken from 14 identified IDCM patients and 14 controls. The RT-PCR results revealed no significant differences in the expression of the genes APP, MYH10, and MYH11 between the two groups. By contrast, the STAT1, IGF1, CCND1, and VEGFA genes were overexpressed in patients more than in controls. The highest expression was found for VEGFA, followed by CCND1 (p < 0.001). Overexpression of these genes may contribute to disease progression in patients with IDCM. However, more patients and genes need to be analyzed in order to achieve more robust results.

Association between MMP2 gene polymorphisms and dilated cardiomyopathy in a Chinese Han population.

Dilated cardiomyopathy (DCM) belongs to the common types of cardiomyopathies. The pathogenesis remains unclear despite the fact that various genes have been found associated with DCM. MMP2 is a zinc-dependent and calcium-containing secreted endoproteinases, which could cleave a broad spectrum of substrates including extracellular matrix components and cytokines. It has proved to play an important role in the cardiovascular diseases. This study aimed to investigate the potential role of MMP2 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population. A total of 600 idiopathic DCM patients and 700 healthy controls were enrolled. Patients with contact information were followed up for a median period of 28months. Three tagged single nucleotide polymorphisms (rs243865, rs2285052, and rs2285053) in the promoter of MMP2 gene were genotyped. A series of function analysis were conducted to illuminate the underlying mechanism. The frequency of rs243865-C allele was increased in DCM patients when compared with healthy controls (P=0.001). Genotypic frequencies of rs243865 were associated with the susceptibility of DCM in the codominant, dominant, and overdominant models (P<0.05). Besides, rs243865-C allele presented a correlation with the poor prognosis of DCM patients in both dominant (HR=2.0, 95% confidence interval [CI]=1.14-3.57, P=0.017) and additive (HR=1.85, 95% CI=1.09-3.13, P=0.02) model. The statistical significance remained after adjustment for sex, age, hypertension, diabetes, hyperlipidaemia, and smoking status. There were significant differences in left ventricular end-diastolic diameter and left ventricular ejection fraction between rs243865-CC and CT genotypes. Functional analysis indicated that rs243865-C allele increased luciferase activity and the mRNA expression level of MMP2 by facilitating ZNF354C binding. Our study suggested that MMP2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese Han population.

Peak exercise myocardial deformation indices during cardiopulmonary exercise testing are associated with exercise capacity and ventilatory efficiency in patients with dilated cardiomyopathy.

Little is known about the exercise-induced changes in the multidimensional mechanical properties of the heart. We aimed to evaluate the myocardial deformation indices (MDI) at rest and their response at peak exercise during the same cardiopulmonary exercise testing (CPET) session, investigating their relationship to exercise capacity and ventilatory sufficiency in dilated cardiomyopathy (DCM) patients. We evaluated left ventricular (LV) function using speckle tracking imaging (STI) at rest and peak exercise during the same CPET session in 57 idiopathic DCM patients in New York Heart Association (NYHA) I-II class [54 ± 12 years, 42 males, ejection fraction (EF) 33 ± 9%]. We measured global longitudinal strain (GLS), longitudinal strain rate at systole (LSRS) and diastole (LSRD), and circumferential strain rate (CircS). Resting GLS, LSRS, and LSRD were impaired compared with the predicted values but were improved at peak exercise (p < 0.001). All MDI at rest and/or at peak exercise were related to several CPET-derived parameters, including peak VO2, load, O2 pulse, and VE/VCO2 slope. Peak exercise LSRS > -1.10 sec-1 (AUC = 0.80, p < 0.001) and GLS > -13% (AUC = 0.81, p = 0.002) predicted impaired exercise capacity (peak VO2 < 20 ml/min/kg) and ventilatory inefficiency (VE/VCO2 slope>34). In multiple regression analysis, peak exercise LSRS and GLS were independently related to the peak VO2 (Beta = -0.39, p = 0.003) and VE/VCO2 slope (Beta = 0.35, p = 0.02), respectively. Peak exercise LSRS and GLS in NYHA I-II DCM patients subjected to CPET were associated with aerobic exercise capacity and ventilatory efficiency. Consequently, LSRS and GLS at peak exercise, through their association with CPET-derived CV risk indices, may underline the severity of heart failure and predict future CV events in this DCM population.

The complete reversal effect following angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers after the primary diagnosis of dilated cardiomyopathy.

Whether combination administration of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and beta-blockers (BBs) has a "reversal" effect on cardiac structure and function for first-diagnosed idiopathic dilated cardiomyopathy (FSIDCM) patients with unclear etiologies and inducements is unknown. We studied the effect of the protocol on FSIDCM patients. The effect was investigated in 26 FSIDCM patients. The criteria of "complete reversal" included left ventricular end-diastolic diameter (LVEDD) ≤50 mm for females or ≤55 mm for males and left ventricular ejection fraction (LVEF) ≥45%; the criteria of "partial reversal" was the decreased rate of LVEDD (ΔLVEDD) >10% or the increase rate of LVEF (ΔLVEF) >10%; the criteria of "no reversal" included LVEDD >50 mm for females or >55 mm for males and ΔLVEDD <10%, and LVEF <45% and ΔLVEF <10%. Within the follow-up period, nine patients showed "complete reversal," eight "partial reversal," and nine "no reversal." Improvements in echocardiogram parameters were the most significant in "complete reversal" patients (P < 0.001), followed by "partial reversal" and "no reversal" patients (P < 0.05). The QRS (Q wave, R wave, S wave) duration and symptoms duration in "complete reversal" patients were the shortest, followed by "partial reversal" and "no reversal" patients. ACEIs or ARBs and BBs have a "complete reversal" effect on the left ventricular size and function of some FSIDCM patients. Patients with a narrow QRS and short symptom duration may have a good response.

Socio-demographic Characteristics of Idiopathic Dilated Cardiomyopathy Patients

Background: Idiopathic Dilated Cardiomyopathy(DCM) is generally an irreversible heart muscle disease with approximate prevalence of 1:2500 and amongst the most frequent cause of heart transplantation. This study was conducted to evaluate the socio-demographic characteristics of Idiopathic Dilated Cardiomyopathy patients in a tertiary care hospital.Material and Methods: This was a cross sectional study carried out in the Department of Cardiology at PGIMER, Chandigarh. A total of 34 patients aged between 20-60 years, diagnosed with idiopathic dilated cardiomyopathy from outpatient departments and inpatient wards scrutinized following protocoled set exclusion criteria were evaluated.Results: Among the total 34 patients 25 (73.5%) were males and 9 (26.5%) were females (M:F=2.7:1). Among them 23 (67.6%) were less than 40 years old while 11 (32.4%) were &gt;40 years old. The mean age of the patients was 40.44 (S.D.± 10.42). Total patients with LVEF less than 25% were 18, out of which 3 (16.7%) were female and 15 were male (83.3%). Among these 3 (16.7%) were &gt;40 years and 15 were less than 40 years (83.3%). Total patients with LVEF&gt;25% were 16, out of which 10 males (62.5%) and 6 females (37.5%).Among these 8 (50%) were &gt;40 years and 8 were less than 40 years (50%). Total patients with RVEF less than35% were 11, out of which 2 (18.2%) were female and 9 were male (81.8%). Among these 3 (27.3%) were &gt;40 years and 8 were less than 40 years (72.7%). Total patients with RVEF&gt;35% were 23, out of which 16 males (69.6%) and 7 females (30.4%). Among these 8 (34.8%) were &gt;40 years and 15 were less than 40 years (65.2%).Conclusion:Present study concluded that most of patients ofIdiopathic Dilated Cardiomyopathy patients were males and less than 40 years old.

Endogenous assessment of late gadolinium enhancement grey zone in patients with non-ischaemic cardiomyopathy with T1ρ and native T1 mapping.

This study aims to validate and compare the feasibility of T1ρ and native longitudinal relaxation time (T1) mapping in detection of myocardial fibrosis in patients with non-ischaemic cardiomyopathy, focusing on the performance of both methods in identifying late gadolinium enhancement (LGE) grey zone. Twenty-seven hypertrophic cardiomyopathy (HCM) patients, 16 idiopathic dilated cardiomyopathy (DCM) patients, and 18 healthy controls were prospectively enrolled for native T1 and T1ρ mapping imaging and then all the patients underwent enhancement scan for LGE extent and extracellular volume (ECV) values. In LGE positive patients, the LGE areas were divided into LGE core (6 SDs above remote myocardium) and grey zone (2-6 SDs above remote myocardium) according to the signal intensity of LGE. Both HCM and DCM patients showed significantly higher native T1 values and T1ρ values than controls no matter the presence of LGE (all P < 0.01). There were significant differences in native T1 and T1ρ values among four different types of myocardia (LGE core, grey zone, remote area and control, P < 0.0001). However, the T1ρ values of grey zone were significantly higher than control (P < 0.01), while the native T1 values were not (P = 0.089). T1ρ values were significantly associated with both native T1 values (r = 0.54, P < 0.001) and ECV values (r = 0.54, P < 0.001). T1ρ mapping is a feasible method to detect myocardial fibrosis in patients with non-ischaemic cardiomyopathy no matter the presence of LGE. Compared with native T1, T1ρ may serve as a better discriminator in the identification of LGE grey zone.

Matrix Metalloproteinase 2 and 9 Enzymatic Activities are Selectively Increased in the Myocardium of Chronic Chagas Disease Cardiomyopathy Patients: Role of TIMPs.

Chronic Chagas disease (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis compared to other cardiomyopathies. We show the expression and activity of Matrix Metalloproteinases (MMP) and of their inhibitors TIMP (tissue inhibitor of metalloproteinases) in myocardial samples of end stage CCC, idiopathic dilated cardiomyopathy (DCM) patients, and from organ donors. Our results showed significantly increased mRNA expression of several MMPs, several TIMPs and EMMPRIN in CCC and DCM samples. MMP-2 and TIMP-2 protein levels were significantly elevated in both sample groups, while MMP-9 protein level was exclusively increased in CCC. MMPs 2 and 9 activities were also exclusively increased in CCC. Results suggest that the balance between proteins that inhibit the MMP-2 and 9 is shifted toward their activation. Inflammation-induced increases in MMP-2 and 9 activity and expression associated with imbalanced TIMP regulation could be related to a more extensive heart remodeling and poorer prognosis in CCC patients.

Association of telomere length with diabetes mellitus and idiopathic dilated cardiomyopathy in a South Indian population: A pilot study

Telomere shortening has been associated with ageing and with many age-related diseases including cancer, coronary artery disease, heart failure and diabetes. We sought to investigate the link between telomere shortening and age-related diseases like type 2 diabetes mellitus (DM) (without any complications: DM; with neuropathic complication: DN) and idiopathic dilated cardiomyopathy (IDCM) in south Indian population. We compared telomere lengths of blood lymphocytes taken from patients with associated age-related diseases, namely DM (n = 47), DN (n = 52) and IDCM (n = 34) and controls (n = 46). In addition, we evaluated the relationship between echocardiographic left ventricular ejection fraction (LVEF), left ventricular end diastolic and systolic diameters (LVEDd and LVESd) and telomere length in IDCM patients. Telomere length negatively correlated with age in the cohorts with diabetes and IDCM, and in controls. Average telomere length in diabetes and IDCM patients was significantly shorter than that of controls either before or after adjustments for age and sex. Duration of diabetes in patients with type 2 diabetes did not correlate with telomere length. No correlation was found between the length of telomeres and echocardiography parameters like LVEF, LVEDd and LVESd in IDCM patients. Though echocardiographic characteristics of IDCM did not correlate with telomere length, telomere shortening was found to be accelerated in diabetes (both DM and DN) and IDCM in a south Indian population. Neuropathic complication in diabetes had no effect on telomere shortening. While telomere shortening is a cause or a consequence of diabetic and cardiac pathology remains further investigation, the current study substantiates the usefulness of telomere length measurements as a marker in conjunction with other biochemical markers of age-related diseases.

Altered Aortic Hemodynamics and Relative Pressure in Patients with Dilated Cardiomyopathy

Ventricular-vascular interaction is central in the adaptation to cardiovascular disease. However, cardiomyopathy patients are predominantly monitored using cardiac biomarkers. The aim of this study is therefore to explore aortic function in dilated cardiomyopathy (DCM). Fourteen idiopathic DCM patients and 16 controls underwent cardiac magnetic resonance imaging, with aortic relative pressure derived using physics-based image processing and a virtual cohort utilized to assess the impact of cardiovascular properties on aortic behaviour. Subjects with reduced left ventricular systolic function had significantly reduced aortic relative pressure, increased aortic stiffness, and significantly delayed time-to-pressure peak duration. From the virtual cohort, aortic stiffness and aortic volumetric size were identified as key determinants of aortic relative pressure. As such, this study shows how advanced flow imaging and aortic hemodynamic evaluation could provide novel insights into the manifestation of DCM, with signs of both altered aortic structure and function derived in DCM using our proposed imaging protocol.Graphic r

Circulating circRNA as biomarkers for dilated cardiomyopathy etiology

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing — involving genetics, imaging, or cardiovascular techniques — makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNAs), a leading research topic, remain mostly unexplored in DCM. We aimed to assess whether peripheral circRNAs are expressed differentially among etiology-based DCM. The study was based on a case–control multicentric study. We enrolled 130 subjects: healthy controls (n = 20), idiopathic DCM (n = 30), ischemic DCM (n = 20), and familial DCM patients which included pathogen variants of (i) LMNA gene (n = 30) and (ii) BCL2-associated athanogene 3 (BAG3) gene (n = 30). Differentially expressed circRNAs were analyzed in plasma samples by quantitative RT-PCR and correlated to relevant systolic and diastolic parameters. The pathophysiological implications were explored through bioinformatics tools. Four circRNAs were overexpressed compared to controls: hsa_circ_0003258, hsa_circ_0051238, and hsa_circ_0051239 in LMNA-related DCM and hsa_circ_0089762 in the ischemic DCM cohort. The obtained areas under the curve confirm the discriminative capacity of circRNAs. The circRNAs correlated with some diastolic and systolic echocardiographic parameters with notable diagnostic potential in DCM. Circulating circRNAs may be helpful for the etiology-based diagnosis of DCM as a non-invasive biomarker.Key messagesThe limitations of cardiac diagnostic imaging and the absence of a robust biomarker reveal the need for a diagnostic tool for dilated cardiomyopathy (DCM).The circular RNA (circRNA) expression pattern is paramount for categorizing the DCM etiologies.Our peripheral circRNAs fingerprint discriminates between various among etiology-based DCM and correlates with some echocardiographic parameters.We provide a potential non-invasive biomarker for the etiology-based diagnosis of LMNA-related DCM and ischemic DCM.

Cardiac mitofusin-1 is reduced in non-responding patients with idiopathic dilated cardiomyopathy

Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the β-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients.

Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial.

AimsPrevious uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)‐related dilated cardiomyopathy (DCM). This randomized, double‐blind, placebo‐controlled, single‐centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.Methods and resultsFifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6‐min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end‐diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (−7;5) vs. placebo −2 (−6;6), P = 0.904] and LVEDV (IVIg −16 ± 49 mL/m2 vs. placebo −29 ± 40 mL/m2; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.ConclusionIntravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.Clinical Trial Registration: ClinicalTrials.gov ID NCT00892112.

Abstract 15126: Myocardial Tissue Reverse Remodeling After Guideline-directed Medical Therapy in Idiopathic Dilated Cardiomyopathy

Background: The prognosis of idiopathic dilated cardiomyopathy (DCM) patients has improved remarkably in the recent decades with guideline-directed medical therapy (GDMT) and some patients undergo left ventricular reverse remodeling (LVRR). Objectives: We aim to study the dynamic changes of myocardial tissue characteristics by cardiovascular magnetic resonance (CMR), and investigate the association between myocardial tissue characteristics and cardiac functional remodeling in DCM patients after treatment. Methods: A total of 133 prospectively and consecutively enrolled DCM patients underwent baseline and follow-up CMR examinations with a median interval of 13.7 months (IQR: 12.2-18.5 months). The CMR protocol included cine, late gadolinium enhancement (LGE), pre- and post-contrast T1, and T2 mapping. LVRR was defined as an absolute increase in LV ejection fraction (EF) of &gt;10% to a final value of ≥ 35% with a relative decrease in LV end-diastolic volume (EDV) of &gt;10%. Results: Forty-two (31.6%) patients experienced LVRR during follow-up. At baseline, new onset heart failure, lower LVEF and the absence of LGE were independent predictors of LVRR. Patients with LVRR showed significant decrease of myocardial native T1, indexed matrix and cell volumes, while patients without LVRR also showed significant albeit smaller decrease of native T1 and indexed matrix and cell volumes. The changes of myocardial tissue characteristics were significantly correlated with the improvement of LVEF and indexed LVEDV. Conclusions: In idiopathic DCM patients, significant improvements in myocardial tissue characteristics were observed and accompanied with the improvement in LVEF and reduction in indexed LVEDV after GDMT.

Abstract 14563: Improved Outcomes in Patients With Anthracycline-Induced Cardiomyopathy Undergoing Left Ventricular Assist Devices: 10-Year Longitudinal INTERMACS Study

Introduction: Anthracycline-induced cardiomyopathy (AC-CM) presenting as end-stage heart failure may require mechanical circulatory support. Hypothesis: We hypothesize that there is no difference in outcomes after LVAD placement in those with AC-CM compared to other forms of cardiomyopathy. Methods: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) dataset spanning from 2008 to 2017 was utilized to identify adult AC-CM patients undergoing continuous flow LVAD implantation excluding those who required concomitant cardiac procedures and right ventricular support (RVS). AC-CM patients were compared to those undergoing LVAD placement due to idiopathic dilated cardiomyopathy (IDM) and ischemic cardiomyopathy (ICM). Primary outcome of overall mortality was studied using Cox-proportional hazards model. Secondary outcomes of first infection, ischemic stroke, major bleeding and subsequent RVS were evaluated using Fine-Gray competing risk model accounting for appropriate competing risks. Subgroup analysis based on gender, race, ethnicity, and use of pre-transplant goal directed medical therapy (GDMT) for systolic heart failure was performed. Result: Overall, 248 AC-CM patients underwent continuous flow LVADs in the 10-year period. At 12-months, 85.1% of AC-CM, 86.0% of IDM and 80.2% of ICM patients were alive (log-rank P &lt; 0.001). There was no difference in mortality compared to ICM and IDM ( P &gt; 0.05). However, pre-LVAD GDMT improved mortality in only the AC-CM cohort when compared to those patients who were not on GDMT (adjusted hazards ratio (HR): 0.44; confidence interval (CI): 0.19 - 0.99). AC-CM patients had a higher risk of major bleeding compared to IDM patients (HR: 1.23; CI: 1.01 - 1.50). AC-CM patients had lower risk of stroke compared to ICM patients (HR: 0.31; CI: 0.15 - 0.62). There was no difference in the three subtypes of cardiomyopathy in hazards of first infection or subsequent RVS. Conclusion: Survival rates are similar in AC-CM, ICM and IDM patients who received continuous flow LVAD therapy in the contemporary era. There is improved mortality benefit in AC-CM patients who are on GDMT before LVAD. Further research into bleeding and stroke related disparities is warranted.

Abstract 15116: The Prognostic Value of Left Ventricular Mechanical Dyssynchrony in Patients With Idiopathic Dilated Cardiomyopathy

Backgrounds: The mechanical dyssynchrony has been commonly observed in idiopathic dilated cardiomyopathy (DCM) patients, and several cardiac magnetic resonance (CMR) imaging techniques were used to evaluate the mechanical dyssynchrony. Standard deviation of time-to-peak (T2Psd) and uniformity ratio estimate (URE) indices are two widely used parameters to reflect the incoordinate movement of the left ventricle. However, the prognostic value of mechanical dyssynchrony in DCM patients is not clear. Methods and Results: We prospectively enrolled 402 DCM patients undergoing CMR imaging between Jun 2012 to Sep 2018. Mechanical dyssynchrony was measured as T2Psd and URE indices by CMR deformable registration algorithm (DRA) analysis. The primary endpoint was defined as all-cause mortality and heart transplantation, and the secondary endpoint was a combination of primary endpoint, aborted sudden cardiac death, and heart failure readmission. Univariate and multivariate Cox regression analyses were performed to identify the association between variables and outcome. Survival curves were obtained by Kaplan-Meier survival analysis and compared by log-rank test. During a median follow-up of 25.1 months (IQR: 16.2-41.6), there were 57 patients reached primary endpoints, and secondary endpoints occurred in 132 patients. Circumferential uniformity ratio estimate (CURE) at basal, mid and apical level, radial uniformity ratio estimate (RURE)at mid and apical level and longitudinal uniformity ratio estimate (LURE) were significantly worse in patients with primary endpoint compared to patients without primary endpoint. While no significant differences were observed regarding the T2Psd value between patients with and without primary endpoints. In multivariate analysis, CURE at apical level was independently associated with primary endpoints (HR 0.214, P=0.005) and secondary endpoints (HR 0.402, P=0.018). Furthermore, among patients with LVEF &lt;35% or presence of LGE, those with decreased CURE at apical level (&lt;0.917) showed a significantly higher rate of adverse outcome. Conclusion: The CURE at apical level is an independent predictor of adverse cardiac events in DCM patients. Compared with T2Psd, URE index is a better predictor of adverse events.

The expression of NKT like cells and NK cells in the peripheral blood among patients with idiopathic dilated cardiomyopathy (IDCM)

Abstract Introduction Dilated cardiomyopathy is associated with various immunological abnormalities, such as decreases in the activity and subsets of suppressor T cells and in the activity of natural killer cells, suggesting the involvement of immunological mechanisms in the pathogenesis of this disease. However, the role of NKT like cells and NK cells in the pathogenesis of idiopathic dilated cardiomyopathy remains still uncertain. The aim of the study was to compare the frequencies of peripheral NKT like cells and NK cells among patients with IDCM to healthy controls. Methods The frequencies of NKT like cells and NK cells were measured by flow of cytometry among 50 patients with IDCM from Cardiology Clinic in Lublin. The control group consisted of 50 healthy sex- and age- matched volunteers. The diagnosis of IDCM was based on the common known ESC Guidenlines 2018 criteria. Statistical analysis of the results was conducted using IBM program. A value of p less than 0.05 was considered statistically significant. Results The frequency (%) (mean ± SD) of NK cells (CD3+/CD16+CD56+) was significantly lower (p≤0.001) in IDCM group (12.0±4.5) when compared to control group (15.6±3.4). The frequency (%) (mean ± SD) of NK T like cells (CD3+/CD16+CD56+) was significantly elevated (p≤0,04) in IDCM group (4,66±3,4) in comparison to the control group (3,23±1,7). Conclusions Our findings of the abnormalities in immune cells distribution in peripheral blood of IDCM patients suggest that IDCM development and progression is related to the dysregulation of the immune system. The decreases in the activity in the NK cells among patients with IDCM might indicate chronic myocarditis and lymphocyte infiltration in the myocardium. Moreover, the elevation of NKT like cells could be a result of prolonged exposure to pathogen in which TCD3+ cells become involved more than less mature NK cells in engaging specific immunity response. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Medical University in Lublin, Grant for Young Reserchers