Coronary microcirculation changes in non-ischemic dilated cardiomyopathy identified by novel perfusion CT.

Dilated cardiomyopathy (DCM) is a subtype of cardiomyopathy characterized by its heterogeneous etiology. There is a pressing need for guidance in clinical treatment and prognosis prediction. In this study, we conducted a comprehensive profiling of serum proteome in DCM patients, comparing it with both healthy individuals and patients with ischemic cardiomyopathy (ICM), to identify serological characteristics unique to DCM. By analyzing serum proteomics data from 113 DCM patients, we successfully classified DCM into four distinct subtypes: Catabolism and Immunity, Cell Adhesion and Regeneration, Immunity and Inflammation, and Metabolism and Antibiotic Response. Although these subtypes did not show significant associations with prognosis, they may reflect the complex etiology underlying DCM. Additionally, we identified a protein interaction network centered around BCHE, APOC3, and TTR, which was significantly correlated with better prognosis. Conversely, a network involving FCRL3, JCHAIN, and lGKV3-20 was linked to poorer outcomes and increased mortality risk. Notably, four proteins-H6PD, FGB, FGG, and OlT3-were significantly associated with recurrence of DCM events, highlighting their potential as biomarkers for monitoring disease progression. Based on these findings, we developed prediction models for recurrence and death within a three-year period, achieving accuracies of 91.3% and 73.4%, respectively. Furthermore, we identified some other proteins, such as ANG, as potential independent indicators for predicting the efficacy of trimetazidine therapy, leading to establishment of a predictive model specifically for trimetazidine efficacy, which achieved a prediction accuracy of 81.5%. These results not only deepen our understanding of the biological underpinnings of dilated cardiomyopathy (DCM) but also emphasize the importance of serum proteomics in improving the prognostic management of DCM patients, providing a potential basis for more personalized therapeutic strategies. Figure Captions Fig. 1 A Study design overview with control (n=30), ICM (n=30), and DCM (n=113) groups, including 2-3 years of follow-up and a proteomic analysis workflow. B Venn diagram showing the overlap of identified proteins among control, ICM, and DCM groups. C Intensity distribution of identified proteins across DCM, ICM, and control groups. D-E Volcano plots showing protein expression differences between DCM (or ICM) and control groups. F Relative intensity of differentially expressed proteins between DCM and control groups. Significant differences between groups are indicated by asterisks (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001). Fig. 2 A Heatmap showing clinical characteristics and proteomic data across four DCM subtypes. B Functional annotation of proteins associated with each DCM subtype, categorized into four biological process subgroups. C-F Heatmaps of proteins specific to subtypes 1, 2, 3, and 4.Study Design and Proteomic Profile Subtype Classification of DCM

Comparison of Muscle Sympathetic Activity in Ischemic and Nonischemic Heart Failure

Lipid-soluble vitamins are essential micronutrients that play a vital role in processes such as growth, reproduction, immune regulation, antioxidant defense, anti-inflammatory response and cardiovascular health. This study aimed to evaluate the plasma levels of retinol, cholecalciferol, α-tocopherol and phylloquinone in dogs with dilated cardiomyopathy (DCM). Six dogs diagnosed with DCM and ten healthy control dogs were selected based on clinical, echocardiographic, electrocardiographic and radiographic examinations. Chromatographic analysis was performed to analyze the content of lipid-soluble vitamins. The mean plasma retinol levels were 0.0285 μg/mL and 0.0495 μg/mL in the DCM and control groups, respectively, and the mean cholecalciferol levels were 0.0739 μg/mL and 0.1045 μg/mL in the DCM and control groups, respectively. Retinol and cholecalciferol levels were both statistically lower in the DCM group than in the control group (p < 0.05). The mean plasma α-tocopherol levels were 0.3103 and 0.4322 μg/mL, and the mean plasma phylloquinone levels were 0.03780 and 0.04082 μg/mL in the DCM and control groups, respectively. However, no statistical significance was observed between the two groups for α-tocopherol or phylloquinone levels. Based on our findings, alterations in vitamin A and D metabolism could be associated with the development of idiopathic DCM in dogs. However, given the limited sample size, further investigation in larger populations is needed.

In routine procedures, patient's arms are positioned above their heads to avoid potential attenuation artifacts and reduced image quality during gated myocardial perfusion imaging (G-MPI). However, it is difficult to achieve this action in the acute period following pacemaker implantation. This study aimed to explore the influence of arm positioning on myocardial perfusion imaging (MPI) in different types of heart disease. This study was conducted retrospectively. A total of 123 patients were enrolled and underwent resting G-MPI using a standard protocol with arms positioned above their heads and again with their arms at their sides. All individuals were divided into 3 groups: the normal group, the obstructive coronary artery disease (O-CAD) group, and the dilated cardiomyopathy (DCM) group. The G-MPI data were measured by QGS software and Emory Reconstruction Toolbox, including left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), end-systolic volume (ESV), extent, total perfusion deficit (TPD), summed rest score (SRS), scar burden, phase standard deviation (SD), and phase histogram bandwidth (BW). In total, extent, TPD, EDV, ESV, LVEF, systolic SD, systolic BW, diastolic SD, and diastolic BW were all significantly different between the 2 arm positions (all P<0.01). On the Bland-Altman analysis, both EDV and ESV with the arm-down position were significantly underestimated (P<0.001). Meanwhile, TPD, extent, and LVEF with the arm-down position were significantly overestimated (P<0.05). Systolic SD, systolic BW, diastolic SD, and diastolic BW were systematically overestimated (P<0.001). In the DCM group (n=52), EDV, ESV, systolic SD, systolic BW, diastolic SD, and diastolic BW were identified as significantly different by the paired t-test between the 2 arm positions (P<0.05). In the O-CAD group (n=32), scar burden, ESV, LVEF, and diastolic BW were significantly different between the 2 arm positions (P<0.05). Systolic and diastolic dyssynchrony parameters and most left ventricular (LV) functional parameters were significantly influenced by arm position in both normal individuals and patients with heart failure (HF) with different pathophysiologies. More attention should be given to LV dyssynchrony data during clinical evaluation of cardiac resynchronization therapy (CRT) implantation procedure.

Background: The clinical features of patients with cardiomyopathy, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or restrictive cardiomyopathy (RCM), have not been recently elucidated in Japan.Methods and Results: We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM from 2003 to 2014 and in HCM and RCM from 2009 to 2014 from the national registry of clinical personal records organized by the Japanese Ministry of Health, Labour and Welfare. In all, 44,136 patients were included in this registry: 40,537 with DCM, 3,553 with HCM, and 46 with RCM. The median age at diagnosis was older for DCM and HCM than RCM (54 and 55 vs. 42 years, respectively). Male patients accounted for 74.6%, 58.7%, and 60.9% of the DCM, HCM, and RCM groups, respectively. NYHA functional Class III–IV was found in 26.9%, 11.3%, and 58.1% of patients in the DCM, HCM, and RCM groups, respectively. In the DCM group, the rates of β-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription were 69% and 76%, respectively. In regional subgroup analysis, the median age at diagnosis of DCM and HCM was younger in the Kanto region. A family history of HCM was less frequent in the Hokkaido/Tohoku region.Conclusions: The national registry of clinical personal records of cardiomyopathy could provide important information regarding the demographics, clinical characteristics, and management of cardiomyopathy throughout Japan.

Introduction: The main cause of cardiac transplantation is dilated cardiomyopathy (DCM), in which there are ventricular dilation and systolic dysfunction, leading to congestive heart failure. Ventricular remodeling involves activation of the sympathetic nervous and renin-angiotensin- aldosterone systems. As such, classic treatments include angiotensin-converting enzyme inhibitors (ACEI), beta-blockers and mineralocorticoid receptor antagonists. Once such treatments only delay the development of the disease, it is important to look for better therapeutic options. Experimental models demonstrated the benefits of sympathetic blockade on preserving ventricular function and preventing left ventricle remodeling after myocardial infarction. Objective: We evaluated the influence of bilateral thoracic sympathectomy on left ventricle remodeling and function in a rat model of doxorubicin induced DCM. Methodology: Animals were randomly divided into 4 groups of 7 rats each. DCM only, bilateral sympathectomy (BS) with DCM, ACEI with DCM and also a negative control group (SHAM). DCM was inducted in the experimental groups through weekly intraperitoneal injection of doxorubicin. Fifteen days after the beginning of DCM induction, bilateral sympathectomy was performed by chemical sclerosis of stellate ganglion with ethanol in the BS group. From this same time point until the end of experimental protocol, animals of the ACEI group received daily, through water ingestion, a enalapril maleate dilution. Ten weeks later, left ventricular function was evaluated with the use of a microtip pressureconductance catheter. Also, extracellular fibrosis were evaluated and BCL-2 expression on myocardial tissue were quantified. Partial Results: DCM group showed an increased left ventricular (LV) end-diastolic volume in relation to Sham group(p=0.034). Also, a significant decrease was observed in LV ejection fraction in DCM group, while bilateral sympathectomy were able to preserve this parameter (p=0,001). Furthermore, both treated groups showed an increased LV stroke work compared to DCM group (p=0,002). Myocardial extracellular fibrosis were more present in control group, whereas both BS and ACE inhibitor treatments reduced the areas of fibrotic tissue (p&lt;0,0001), which can be associated with increased expression of anti-apoptotic BCL-2 in treated groups (p=0,0004). Discussion and Conclusion: Sympathetic blockade was able to suppress myocardial tissue fibrosis, most likely due to increasing anti-apoptotic BCL-2 expression. Moreover, LV function was maintained as observed through LV ejection fraction,stroke work and cardiac efficiency levels. Although ACE inhibitor was also able to inhibit extracellular fibrosis and increase BCL- 2 expression, cardiac function has not been preserved as in BS group. Therefore, we conclude that BS was able to decrease myocardial tissue deterioration and also to preserve LV in a doxorubicin model of DCM in rats. Keywords: Sympathectomy; Cardiomyopathy; Cardiac transplantation; Doxorubicin.

Risk Assessment of Ventricular Arrhythmias in Patients with Nonischemic Dilated Cardiomyopathy by Strain Echocardiography

To explore the role of T1 mapping and late gadolinium enhancement (LGE) for detection of dilated cardiomyopathy (DCM). Thirty-two DCM patients detected by ultrasonic testing with unknown origin heart failure from April 2018 to November 2019 were involved. In addition, they were compared with 18 physical examiner under cardiac magnetic resonance imaging (CMRI) in the same period. Phillip's Ingenia 3.0T MRI was used to examine heart function, plain scan included cine, T2 weighted imaging (T2WI) and pre-contrast native T1 mapping. The enhancement scan included perfusion weighted imaging, LGE imaging and post-contrast post T1 mapping. Using gadolinium injection, a bolus of 0.1 mL/kg of gadolinium-based contrast followed by a 20 mL saline flush was administered. After a 7-minute later start scanning, delay enhance sequence was started, including 4 layers, 2 cavities and 4 cavities. LGE and T1 mapping results were observed, including cardiac function indexes [left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), valvular regurgitation], cardiac morphological indexes [left ventricular mass (LVM)], histological characteristics (T2WI myocardial signal, presence of perfusion defect and its position and scope, presence of delayed enhancement and its position, shape and scope, pre- and post-contrast T1 values), extracellular volume (ECV) and the accompanying signs (pericardial effusion and pleural effusion). The receiver-operating characteristic curve (ROC) was drawn, the diagnostic value of T1 value of pre-contrast T1 mapping for DCM was evaluated, and the occurrence of clinical endpoint events was observed. There were no statistically significant differences in DCM patients with gender, age, body mass index (BMI), blood pressure, heart rate (HR), hematocrit (HCT), creatinine (Cr), family history of hypertension or heart disease. In DCM group N-terminal brain natriuretic peptide precursor (NT-proBNP) level and proportion of patients with heart function level III, diabetes, smoking history, drinking history and medication history were significantly higher than those in control group. Compared with control group, LVEDV (mL/m2: 234.9±35.9 vs. 121.8±27.6), LVESV (mL/m2: 189.7±42.8 vs. 54.8±17.0), LVM (g: 197.6±56.3 vs. 110.5±22.9), pre-contrast T1 values (ms: 1 332.1±35.9 vs. 1 272.0±47.0), ECV [(45.7±4.9)% vs. (28.0±2.1)%] were significantly increased in the DCM group; LVEF (0.191±0.107 vs. 0.554±0.103), post-contrast T1 values (ms: 453.9±72.7 vs. 493.5±43.9) were significantly decreased (all P < 0.05). In DCM group, the proportions of valvular regurgitation, pericardial effusion and pleural effusion were 25.0%, 18.8% and 25.5%, respectively. ROC curve analysis showed that the cutoff value of pre-contrast T1 values was 1 220.22 ms, the area under ROC curve (AUC) was 0.84 (P = 0.015), the sensitivity and specificity were 77.8% and 88.9%, indicating that pre-contrast T1 values may be a certain prediction for diagnosis of DCM. In 32 patients with DCM, 22 cases (68.8%) had LGE in position wall, interventricular septum, inferior wall or under the epicardium, with local or multiple diffuse, 9 cases (28.1%) were both interventricular septum and inferior wall involved. During an average of 16 months follow-up, 3.1% patients appeared sudden cardiac death. One-stop CMRI can improve the diagnostic efficacy of DCM, and T1 mapping with LGE imaging can improve the diagnostic accuracy, which is very meaningful for diagnosis and follow-up of patients.

0365 : Prognostic value of left atrial volume in patients with non-ischemic dilated cardiomyopathy

This study explored differences in morphology and distribution of myocardial lymphatic drainage ducts in patients with dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM) in end-stage heart failure to reveal the relationship between the morphological distribution characteristics of myocardial lymphatic drainage ducts and different etiologies and these disease courses. Hearts of 24 patients (transplant recipients) who underwent heart transplantation and 1 normal heart were collected. Myocardial tissue from the anterior wall of the ventricle was taken and quickly frozen. Immunohistochemical and Western blotting techniques were used to detect the expression of LYVE-1, Podoplanin, and VEGFR-3 in cardiac tissue. Ink injection, immunohistochemical staining, and immunofluorescence double labeling techniques were used to detect the co-localization of three antibodies in hu-man heart tissue. Masson staining was used to observe the distribution and content of collagen fibers in the heart tissue of transplant recipients. Compared with the normal group, expression levels of LYVE-1 (p<0.05) and VEGFR-3 (p<0.001) in the DCM group were significantly increased. Expression level of LYVE-1 (p<0.05) was significantly increased in the ICM and HCM groups, but there was no significant change in the expression level of VEGFR-3. The expression level of Podoplanin in the normal group was higher than that in the heart failure groups, but the protein ex-pression results were the opposite. The expression levels of LYVE-1 and VEGFR-3 in the DCM and ICM groups showed an increasing trend with the progression of the disease, while the expression levels of Podoplanin showed a decreasing trend. The immunofluorescence results showed that on larger lymphatic vessels, LYVE-1 and VEGFR-3 were expressed on the inner side of the lymphatic lumen, while Podoplanin was expressed on the outer side, and there was co-localization between the two layers. Masson's staining results showed that the degree of myocardial fibrosis in the DCM group (p<0.01) and HCM group (p<0.001) increased, while there was no significant change in the ICM group (p<0.05). Positive expression intensity of LYVE-1, Podoplanin, and VEGFR-3 does not have a consistent quantitative relationship with different types of heart failure and the duration of the disease. The expression of three biomarkers confirms that DCM, ICM, and HCM have increased lymphatic vessel architecture compared to normal hearts, and the number of lymphatic vessels increases with prolongation of disease course.

To analyze myocardial fibrosis in dilated cardiomyopathy (DCM) patients with no late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) using T1 mapping and extracellular volume (ECV) and investigate the potential correlation with left ventricular (LV) dilation and dysfunction. The study included 41 DCM patients without LGE and 79 healthy controls. T1 and ECV were compared between the two groups using multivariable logistic regression analysis. The correlations between histological and functional parameters were evaluated using Pearson's correlation. Mean native myocardial T1 and ECV were significantly higher in the DCM group compared to controls (p ≤ 0.001, respectively). Multivariable logistic regression revealed that ECV (mean, minimum), LV ejection fraction (LVEF), and LV end-diastolic diameter (LVEDD) were independent discriminators for LGE-negative DCM; the area under the curve (AUC) of LVEF, LVEDD, ECV mean, and ECV minimum were 0.97, 0.96, 0.88, and 0.68, respectively. In the DCM group, LVEDD and LVEF were positively and negatively correlated with ECV, respectively. LVEDV index and LV end-systolic volume (LVESV) index were positively correlated with native-T1 and ECV, and the absolute value of LV global strain had a negative correlation with ECV. Early myocardial fibrosis in DCM could be detected by prolonged native T1 and elevated ECV despite the absence of LGE on CMR. Moreover, the change of histological characteristics of myocardium in DCM was correlated with LV dilation and dysfunction. • At an early stage, patients with DCM may have myocardial fibrosis despite the absence of LGE. • T1 mapping and ECV are efficient methods for early detection of potential myocardial fibrosis. • Increased native T1 and ECV are correlated with left ventricular dilation and dysfunction in LGE-negative DCM patients.

The spatial pattern of coronary capillaries in patients with dilated, ischemic, or inflammatory cardiomyopathy

Objective To screen out the specific expression of miRNA in dilated cardiomyopathy (DCM) by miRNA array, and to constructing DCM related gene regulatory network by bioinformatic prediction of the miRNA target genes. Methods Twenty- six patients with DCM and 30 matched healthy controls were included. The extracted and purified plasma RNA was screened by miRNA array. Real time quantitative PCR was used to verify the findings of miRNA array. The miRNA target genes were predicted by bioinformatics, and the DCM related miRNA- Gene- Network was constructed. Results According to the miRNA array, 24 differentially expressed miRNA in DCM were found, including 15 up- regulated miRNA expression and 9 down-regulated miRNA expression. Bioinformatics analysis showed that miR-20a, miR-23a and miR- 24 may play significant role in DCM. Further Real- time PCR found that there was no statistical difference in the miR- 20a expression between the DCM group and the control group (1.29±1.12 vs 1.07±0.74, P=0.557). The expression of miR- 23a and miR- 24 in the DCM group were higher than that in the control group (2.72±1.45 vs 1.19±1.05; 1.91±1.09 vs 0.954±0.81, all P<0.01) , and the difference was statistically significant. Conclusion There is difference in miRNA expression between DCM patients and healthy subjects. The miRNA may be related to DCM, whereas the increased expression of miR-23a and miR- 24 in DCM patients may be the key miRNAs in DCM. Key words: Cardiomyopathy, dilated; MicroRNAs; Oligonucleotide array sequence analysis; Bioinformatics

Left Ventricular Dilatation Impacts Heart Transplant and Death in Left Ventricular Non-Compaction Cardiomyopathy

Dilated cardiomyopathy (DCM) is a well-recognized cause of heart failure in dogs and often act silent killers. Diagnosis with use of ECG and Echocardiography is not a routine in India except at few institutes. This is the first report from Gujarat (India) on diagnostic use of cardiac biomarkers and echocardiography in canine dilated cardiomyopathy in dogs. The study included 9 healthy dogs and 56 confirmed cases of DCM out of which 18 cases were randomly selected for the detailed study. DCM affected dogs showed history and clinical signs of exercise intolerance, dyspnoea, coughing, inappetence, weight loss, abdominal enlargement, vomiting and syncope. The typical clinical features of DCM cases were tachycardia, murmur, pulmonary oedema and muffled heart sound. The heart rate, pulse rate and respiration rate of DCM affected dogs were significantly higher than healthy group with no change in rectal temperature of both groups. The average diastolic blood pressure in DCM group was significantly higher than healthy group. Important ECG findings noticed in DCM group were atrial fibrillation (38.89%), sinus tachycardia (33.33%), ventricular premature complex (16.67%), normal sinus arrhythmia (5.56%) and atrial flutter (5.56%). Significant increased LA/Ao ratio and EPSS along with lowed EF and FS on echocardiography confirmed the cases of DCM. Further, the biomarkers: NT-pro BNP, cTn-I and CPK-MB were found elevated in DCM group than healthy group. Results suggests that dilated cardiomyopathy being the most commonly observed acquired heart disease in middle aged dogs requires awareness in owners for regular checkup to diagnose cases in earlier so that follow-up treatment can be helpful for enhancement of lifespan of affected dogs.