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

Introduction and objectives: 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. Methods: 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. Results: 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. Conclusion: 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.

Construction and evaluation of immune-related diagnostic model in patients with heart failure caused by idiopathic dilated cardiomyopathy.

OBJECTIVE: The purpose of the study was to construct the potential diagnostic model of immune-related genes during the development of heart failure caused by idiopathic dilated cardiomyopathy. METHOD: GSE5406 and GSE57338 were downloaded from the GEO website ( https://www.ncbi.nlm.nih.gov/geo/ ). CIBERSORT was used for the evaluation of immune infiltration in idiopathic dilated cardiomyopathy (DCM) of GSE5406. Differently expressed genes were calculated by the limma R package and visualized by the volcano plot. The immune-related genes were downloaded from Immport, TISIDB, and InnateDB. Then the immune-related differential genes (IRDGs) were acquired from the intersection. Protein-protein interaction network (PPI) and Cytoscape were used to visualize the hub genes. Three machine learning methods such as random forest, logical regression, and elastic network regression model were adopted to construct the prediction model. The diagnostic value was also validated in GSE57338. RESULTS: Our study demonstrated the obvious different ratio of T cell CD4 memory activated, T cell regulatory Tregs, and neutrophils between DCM and control donors. As many as 2139 differential genes and 274 immune-related different genes were identified. These genes were mainly enriched in lipid and atherosclerosis, human cytomegalovirus infection, and cytokine-cytokine receptor interaction. At the same time, as many as fifteen hub genes were identified as the IRDGs (IFITM3, IFITM2, IFITM1, IFIT3, IFIT1, HLA-A, HLA-B, HLA-C, ADAR, STAT1, SAMHD1, RSAD2, MX1, ISG20, IRF2). Moreover, we also discovered that the elastic network and logistic regression models had a higher diagnostic value than that of random forest models based on these hub genes. CONCLUSION: Our study demonstrated the pivotal role of immune function during the development of heart failure caused by DCM. This study may offer new opportunities for the detection and intervention of immune-related DCM.

Liver T1 Mapping Derived From Cardiac Magnetic Resonance Imaging: A Potential Prognostic Marker in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Hepatic alterations are common aftereffects of heart failure (HF) and ventricular dysfunction. The prognostic value of liver injury markers derived from cardiac MRI studies in nonischemic dilated cardiomyopathy (DCM) patients is unclear. PURPOSE: Evaluate the prognostic performance of liver injury markers derived from cardiac MRI studies in DCM patients. STUDY TYPE: Prospective. POPULATION: Three hundred fifty-six consecutive DCM patients diagnosed according to ESC guidelines (age 48.7 ± 14.2 years, males 72.6%). FIELD STRENGTH/SEQUENCE: Steady-state free precession, modified Look-Locker inversion recovery T1 mapping and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences at 3 T. ASSESSMENT: Clinical characteristics, conventional MRI parameters (ventricular volumes, function, mass), native myocardial and liver T1, liver extracellular volume (ECV), and myocardial LGE presence were assessed. Patients were followed up for a median duration of 48.3 months (interquartile range 42.0-69.9 months). Primary endpoints included HF death, sudden cardiac death, heart transplantation, and HF readmission; secondary endpoints included HF death, sudden cardiac death, and heart transplantation. Models were developed to predict endpoints and the incremental value of including liver parameters assessed. STATISTICAL TESTS: Optimal cut-off value was determined using receiver operating characteristic curve and Youden method. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard. Discriminative power of models was compared using net reclassification improvement and integrated discriminatory index. P value <0.05 was considered statistically significant. RESULTS: 47.2% patients reached primary endpoints; 25.8% patients reached secondary endpoints. Patients with elevated liver ECV (cut-off 34.4%) had significantly higher risk reaching primary and secondary endpoints. Cox regression showed liver ECV was an independent prognostic predictor, and showed independent prognostic value for primary endpoints and long-term HF readmission compared to conventional clinical and cardiac MRI parameters. DATA CONCLUSIONS: Liver ECV is an independent prognostic predictor and may serve as an innovative approach for risk stratification for DCM. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Intestinal microbiota and metabolome perturbations in ischemic and idiopathic dilated cardiomyopathy.

BACKGROUND: Various clinical similarities are present in ischemic (ICM) and idiopathic dilated cardiomyopathy (IDCM), leading to ambiguity on some occasions. Previous studies have reported that intestinal microbiota appeared dysbiosis in ICM, whether implicating in the IDCM remains unclear. The aim of this study was to assess the alterations in intestinal microbiota and fecal metabolites in ICM and IDCM. METHODS: ICM (n = 20), IDCM (n = 22), and healthy controls (HC, n = 20) were enrolled in this study. Stool samples were collected for 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Both ICM and IDCM exhibited reduced alpha diversity and altered microbial community structure compared to HC. At the genus level, nine taxa including Blautia, [Ruminococcus]_torques_group, Christensenellaceae_R-7_group, UCG-002, Corynebacterium, Oceanobacillus, Gracilibacillus, Klebsiella and Citrobacter was specific to ICM, whereas one taxa Alistipes uniquely altered in IDCM. Likewise, these changes were accompanied by significant metabolic differences. Further differential analysis displayed that 18 and 14 specific metabolites uniquely changed in ICM and IDCM, respectively. The heatmap was generated to display the association between genera and metabolites. Receiver operating characteristic curve (ROC) analysis confirmed the predictive value of the distinct microbial-metabolite features in disease status. The results showed that microbial (area under curve, AUC = 0.95) and metabolic signatures (AUC = 0.84) were effective in discriminating ICM from HC. Based on the specific microbial and metabolic features, the patients with IDCM could be separated from HC with an AUC of 0.80 and 0.87, respectively. Furthermore, the gut microbial genus (AUC = 0.88) and metabolite model (AUC = 0.89) were comparable in predicting IDCM from ICM. Especially, the combination of fecal microbial-metabolic features improved the ability to differentiate IDCM from ICM with an AUC of 0.96. CONCLUSION: Our findings highlighted the alterations of gut microbiota and metabolites in different types of cardiomyopathies, providing insights into the pathophysiological mechanisms of myocardial diseases. Moreover, multi-omics analysis of fecal samples holds promise as a non-invasive tool for distinguishing disease status.

Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy.

Our objective was to evaluate the long-term prognostic value of high-sensitivity cardiac troponin-I (hs-cTn-I) in idiopathic dilated cardiomyopathy (DCM). First, patients were divided into an end-event group (n = 55) and a non-end-event group (n = 67). Then, patients were included in the subgroup analysis to compare the diagnostic value of brain natriuretic peptide (BNP) and hs-cTn-I in different populations. hs-cTn-I and BNP concentrations were higher in the end-event group. The Cox regression analysis indicated that high hs-cTn-I was a risk factor for poor long-term prognosis. Receiver operating characteristic analysis showed that the area under the curve (AUC) for hs-cTn-I to predict end events was 0.751, and the AUC for BNP was 0.742. The correlation analysis suggested that hs-cTn-I was related to the percentage change in left ventricular internal diameter at end-diastolic and left ventricular ejection fraction. Subgroup analysis showed that compared with BNP, hs-cTn-I was more suitable for predicting end events in patients with preserved renal function (AUC: 0.853 vs 0.712, P = 0.04). In conclusion, hs-cTn-I is a potential biomarker for evaluating long-term prognosis in idiopathic DCM, and its predictive value is higher than that of BNP in patients with preserved renal function.

Evaluating Goldberger's triad as a marker of congestive heart failure: A systematic review and retrospective study.

BACKGROUND: In 1982, Drs. Barold and Goldberger described an ECG triad associated with left ventricular dysfunction (LVD) consisting of high precordial QRS voltage, low limb lead voltage, and poor precordial R wave progression. Studies have since attempted to replicate the originally reported sensitivity (70%), specificity (>99%), and positive predictive value (PPV, 100%) of Goldberger's triad (GT) with variable results. PURPOSE: To assess sensitivity, specificity and PPV of GT as a screening tool for LVD in the current era. METHODS: We performed: (1) A systematic review of the published studies; (2) Searched our hospital ECG database (GE MUSE) for diagnoses of "low limb-voltage" and "left ventricular hypertrophy" from 2017 to 2022; identified ECGs were analyzed for GT criteria and their medical records were screened for LVD. (3) ECG analysis of patients with known idiopathic LVD for the GT. RESULTS: A total of 11,115 patients from 8 studies were included in the systematic review of published studies and showed widely varying sensitivity, specificity and PPV. A total of 4576 ECGs (in GE MUSE) from 372 patients met initial screening criteria of low limb lead voltage and LVH; only 12 patients had ECGs that satisfied GT. Of these 12, only 1 patient had evidence of LVD, yielding a PPV of 8%. Finally, of the 40 patients with known LVD, only 1 met the ECG criteria for GT, resulting in a sensitivity of 2.5%. CONCLUSION: Our literature review does not support the original results of GT. ECGs from our database that met GT (searched by low limb-voltage and left ventricular hypertrophy) over a span of 5 years were rare. When present, the PPV of GT was 8%. In patients with established LVD, the sensitivity was 2.5%. These data do not validate GT as tool to identify LVD in the current era.

Metabolome Profiling in the Plasma of Dogs with Idiopathic Dilated Cardiomyopathy: A Multiplatform Mass-Spectrometry-Based Approach.

Dilated cardiomyopathy is one of the important diseases in dogs and humans. The second most common cause of heart failure in dogs is idiopathic dilated cardiomyopathy (iDCM), which results in heart failure or sudden cardiac death due to arrhythmia. This study aimed to determine changes in the plasma metabolome of dogs with iDCM compared to healthy dogs. For that purpose, a multiplatform mass-spectrometry-based approach was used. In this study, we included two groups of dogs: 12 dogs with iDCM and 8 healthy dogs. A total of 272 metabolites were detected in the plasma samples of dogs by combining three approaches but four MS-based platforms (GC-MS, LC-MS (untargeted), LC-MS (targeted), and FIA-MS (targeted) methods). Our findings demonstrated changes in the canine plasma metabolome involved in the development of iDCM, including the different concentrations of amino acids, biogenic amines, acylcarnitines, triglycerides and diglycerides, sphingomyelins, and organic acids. The results of this study will enable the detection and monitoring of pathophysiological mechanisms involved in the development of iDCM in the future.

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.

Non-sustained Ventricular Tachycardia as a Presentation of Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare disorder with familial (autosomal dominant) predisposition and can be challenging to diagnose. Non-sustained ventricular tachycardia (NSVT) is a relatively uncommon and short-lived arrhythmia when seen in the general, healthy population. NSVT with a left bundle branch block morphology is usually idiopathic but may also be seen in ARVC. It can also be associated with poorer prognosis and increased mortality. Repetitive monomorphic ventricular ectopic beats may suggest ARVC, but could also be idiopathic. Timely diagnosis is vital due to the unpredictability and progressive nature of ARVC. We present a case of a 40-year-old Caucasian female with heart palpitations and NSVT found on an outpatient Holter monitor, and later found to have clinical and radiological features consistent with ARVC.

Recognition of Pulseless Ventricular Tachycardia Through the Second Analysis of Automated External Defibrillators, Leading to Successful Shock Delivery in a Patient With Dilated Cardiomyopathy: A Case Report.

The use of a defibrillator with a monitor is recommended for the shock indication algorithm for in-hospital cardiac arrest; however, it is likely that many medical facilities are still equipped only with automated external defibrillators (AEDs). We experienced a case of dilated cardiomyopathy (DCM) complicated by pulseless ventricular tachycardia (pVT) in which an AED was used, but shock was deemed unnecessary after the first analysis. We believe that this case is suggestive of resuscitating cardiac arrest, for which defibrillation is indicated and reported here. A 65-year-old man who had DCM and diabetic nephropathy was admitted to our institution because of worsening heart failure. In the hospital, he suddenly had syncope and was diagnosed with cardiac arrest. Thereafter, cardiopulmonary resuscitation (CPR) was performed using an AED, and the monitor on the AED showed pVT. The first analysis of the AED announced unnecessary shock delivery. The pads of the AED were pressed firmly against the chest wall while continuous high-quality CPR was administered for two minutes. The second analysis of the AED revealed the necessity of providing shock for shockable rhythm. The patient experienced the return of spontaneous circulation after shock delivery. We were reminded that there are some clinical cases in which AED shock is not indicated for pVT and that even in such cases, it is important to continue high-quality CPR without panicking.

Clinical characteristics and one-year all-cause mortality outcomes in Africans with dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) is a common cause of heart failure in sub-Saharan Africa (SSA). The affected individuals present with new-onset heart failure with reduced ejection fraction and no identifiable primary or secondary aetiology. We aim to describe the clinical characteristics of participants with heart failure of unknown origin. METHODS: We screened 161 participants with heart failure of unknown origin and prospectively excluded primary and secondary causes of DCM. All study participants were subjected to laboratory biochemical testing, echocardiography, cardiovascular magnetic resonance (CMR) imaging and invasive coronary angiography. RESULTS: The study comprised 93 participants with a mean age of 47.5 SD 13.1 years. Forty-six (56.1%) participants had evidence of late gadolinium enhancement (LGE) on imaging, and LGE was visualised in the mid wall in 28 (61.0%) of these participants. After a median duration of 13.4 months [interquartile range (IQR): 8.8-28.9 months], 18 (19%) participants died. Non-survivors had a higher median left atrial volume index (44.9 mL/m2 (IQR: 34.4-58.7) compared to survivors [32.9 mL/m2 (IQR: 24.5-47.0), p = 0.017)]. The rate of all-cause rehospitalisation was 29.3%, of which 17 of the 22 re-hospitalisations were heart failure related. CONCLUSION: Dilated cardiomyopathy in Africans primarily affects young males. In our cohort, this disease was associated with an all-cause mortality of 19% in one year. In SSA, large multicenter studies are required to investigate this disease's pathogenesis and outcomes.

The genetic basis for adult-onset idiopathic dilated cardiomyopathy in people of African descent.

Cardiomyopathies are a heterogeneous group of cardiac muscle disorders that result in dilated, hypertrophic, or restrictive pathophysiological entities. Dilated cardiomyopathy (DCM) is the most common form in sub-Saharan Africa (SSA). However, population-specific research studies reporting the actual burden of DCM in this region are still lacking. Also, little is known about the genetic basis of DCM in this population, and genetic testing is still not readily accessible. This review describes the common pathogenic genes implicated in DCM globally and discusses the evidence-based management of patients with DCM. We also present a summary of studies describing genes implicated or associated with DCM in patients residing in SSA.

Cardiovascular Magnetic Resonance Imaging Findings in Africans with Idiopathic Dilated Cardiomyopathy.

In sub-Saharan Africa, idiopathic dilated cardiomyopathy (IDCM) is a common yet poorly investigated cause of heart failure. Cardiovascular magnetic resonance (CMR) imaging is the gold standard for tissue characterisation and volumetric quantification. In this paper, we present CMR findings obtained from a cohort of patients with IDCM in Southern Africa suspected of having a genetic cause of cardiomyopathy. A total of 78 IDCM study participants were referred for CMR imaging. The participants had a median left ventricular ejection fraction of 24% [interquartile range, (IQR): 18-34]. Late gadolinium enhancement (LGE) was visualised in 43 (55.1%) participants and localised in the midwall in 28 (65.0%) participants. At the time of enrolment into the study, non-survivors had a higher median left ventricular end diastolic wall mass index of 89.4 g/m2 (IQR: 74.5-100.6) vs. 73.6 g/m2 (IQR: 51.9-84.7), p = 0.025 and a higher median right ventricular end-systolic volume index of 86 mL/m2 (IQR:74-105) vs. 41 mL/m2 (IQR: 30-71), p < 0.001. After one year, 14 participants (17.9%) died. The hazard ratio for the risk of death in patients with evidence of LGE from CMR imaging was 0.435 (95% CI: 0.259-0.731; p = 0.002). Midwall enhancement was the most common pattern, visualised in 65% of participants. Prospective, adequately powered, and multi-centre studies across sub-Saharan Africa are required to determine the prognostic significance of CMR imaging parameters such as late gadolinium enhancement, extracellular volume fraction, and strain patterns in an African IDCM cohort.

Elevated Serum Levels of IgG4 in Patients with Heart Failure with Reduced Ejection Fraction: A Prospective Controlled Study.

(1) Background: Immunoglobulin gamma subclass 4 (IgG4) is a serum protein belonging to the immunoglobulin superfamily. It has a central role in certain immune-mediated conditions defined as IgG4-related disease. There is a paucity of data regarding the potential association of IgG4 and cardiovascular diseases. Our aim is to study the serum levels of IgG4 in patients with ischemic and non-ischemic dilated cardiomyopathy (DCM). (2) Methods: patients with ischemic and non-ischemic DCM were included in this study. Non-ischemic DCM was defined as a left ventricular ejection fraction (LVEF) < 40% without coronary artery disease (CAD). Ischemic DCM was defined as a LVEF < 40% and proven CAD. The serum concentrations of IgG4 were measured by turbidimetry. (3) Results: Overall 98 patients with cardiomyopathy had significantly higher levels of IgG4 compared with the control group (77.4 ± 64.0 vs. 50.3 ± 28.8 mg/dL, p < 0.01). Although there was no difference in the total IgG levels in patients with ischemic DCM, the serum concentrations of IgG4 were significantly higher than the corresponding values in the control group (89.8 ± 67.3 vs. 50.3 ± 28.8 mg/dL; interquartile ranges: 40.4−126.5 vs. 31.8−66.8 mg/dL, p < 0.01). This was altered by gender and smoking. (4) Conclusions: The patients with ischemic DCM had increased serum concentrations of IgG4. Future studies are warranted to explore the potential role of an IgG4-mediated process in patients with heart failure with reduced LVEF.

Double Gain: The Radio Frequency Catheter Ablation of Ventricular Aneurysm Related Recurrent Ventricular Tachycardia on a Tremendous Cardiac Outpouching.

Dilated cardiomyopathy (DCM) is a classic type of non-ischemic cardiomyopathy. Of these, idiopathic cardiomyopathy (IDCM) is a rare type of non-genetic dilated cardiomyopathy. More specifically, the patient had suspected IDCM combined with sustained polymorphic ventricular tachycardia (PMVT) of left ventricular basal segmental origin, cardiac systolic dysfunction and an ejection fraction (EF) of 29%. He had an abnormally large ventricular aneurysm (VA) in the posterior wall of the left ventricle with left ventricular end diastolic dimension (LVDd) of 90 mm. We performed an endocardial radiofrequency catheter ablation (RFCA) of the patient's recurrent ventricular tachycardia (VT) on the basis of an implantable cardioverter (ICD). Although minimally invasive RFCA also carries a high risk, it is currently a two-pronged option to improve the patient's quality of life and to prevent the recurrence of VT. Postoperatively, the patient was routinely given optimal anti-arrhythmic and heart failure (HF) treatments to improve cardiac function as well as being followed up for 9 months. The patient's EF ascended to 36% without any recurrence of VT. In summary, RFCA of suspected IDCM combined with VA and VT of basal area origin would be an effective treatment.

Expression of interleukin 1, interleukin 27, and TNF α genes in patients with ischemic cardiomyopathy versus idiopathic dilated cardiomyopathy: A case-control study.

Background and Aims: Congestive heart failure is a complex multifactorial syndrome due to tissue hypoperfusion that is affected by some factors like inflammatory cytokines. In our study, we investigated the exact gene expression of three inflammatory cytokines in ischemic and idiopathic cardiomyopathy patients. Methods: From 49 studied recipients in the ischemic group, 23 (46.9%) were male and from 40 studied recipients in the idiopathic dilated cardiomyopathy group, 19 (47.5%) were male. For the quantitative analysis of interleukin (IL)-1, IL-27, and tumor necrosis factor (TNF)-α messenger RNAs expression level, the SYBR Green real-time polymerase chain reaction method was performed using SYBRPremix Ex TaqTM II (Tli RNaseH Plus; Takara) and designed primers specific for each gene in an iQ5 thermocycler (BioRad Laboratories) according to the manufacturer's instructions. Results: Our results showed that the expression level of IL-1 and TNF-α were significantly higher in the ischemic patients compared to healthy controls (p < 0.001, p < 0.01, respectively); also, we found higher levels of IL-1 and IL-27 gene expressions in idiopathic patients compared to healthy controls (p < 0.001, p < 0.001, respectively). There were not any significant differences in IL-1, IL-27, and TNF-α expression levels between ischemic patients and idiopathic ones. Conclusion: Although we would introduce IL-1, IL-27, and TNF-α as effective inflammatory cytokines on myocardial functions in ischemic and idiopathic cardiomyopathy patients, there is not any difference between these two groups in gene expression of three main inflammatory cytokines.

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.

Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

Early Prediction of Left Ventricular Reverse Remodeling in First-Diagnosed Idiopathic Dilated Cardiomyopathy: A Comparison of Linear Model, Random Forest, and Extreme Gradient Boosting.

Introduction: Left ventricular reverse remodeling (LVRR) is associated with decreased cardiovascular mortality and improved cardiac survival and also crucial for therapeutic options. However, there is a lack of an early prediction model of LVRR in first-diagnosed dilated cardiomyopathy. Methods: This single-center study included 104 patients with idiopathic DCM. We defined LVRR as an absolute increase in left ventricular ejection fraction (LVEF) from >10% to a final value >35% and a decrease in left ventricular end-diastolic diameter (LVDd) >10%. Analysis features included demographic characteristics, comorbidities, physical sign, biochemistry data, echocardiography, electrocardiogram, Holter monitoring, and medication. Logistic regression, random forests, and extreme gradient boosting (XGBoost) were, respectively, implemented in a 10-fold cross-validated model to discriminate LVRR and non-LVRR, with receiver operating characteristic (ROC) curves and calibration plot for performance evaluation. Results: LVRR occurred in 47 (45.2%) patients after optimal medical treatment. Cystatin C, right ventricular end-diastolic dimension, high-density lipoprotein cholesterol (HDL-C), left atrial dimension, left ventricular posterior wall dimension, systolic blood pressure, severe mitral regurgitation, eGFR, and NYHA classification were included in XGBoost, which reached higher AU-ROC compared with logistic regression (AU-ROC, 0.8205 vs. 0.5909, p = 0.0119). Ablation analysis revealed that cystatin C, right ventricular end-diastolic dimension, and HDL-C made the largest contributions to the model. Conclusion: Tree-based models like XGBoost were able to early differentiate LVRR and non-LVRR in patients with first-diagnosed DCM before drug therapy, facilitating disease management and invasive therapy selection. A multicenter prospective study is necessary for further validation. Clinical Trial Registration:http://www.chictr.org.cn/usercenter.aspx (ChiCTR2000034128).

Cardiac Magnetic Resonance Imaging and Ventricular Tachycardias Involving the Sinuses of Valsalva in Patients With Nonischemic Cardiomyopathy.

OBJECTIVES: The goal of this study was to investigate the relationship between cardiac scar on late gadolinium enhancement cardiac resonance imaging (LGE-CMR) and the presence of ventricular tachycardia (VT) ablation target sites within the sinuses of Valsalva (SV). BACKGROUND: Patients with idiopathic dilated cardiomyopathy (IDCM) often have scarring involving the basal myocardium, including the SV, allowing targeting of VTs from within the SV. METHODS: Forty-three consecutive patients with IDCM underwent a VT ablation procedure with pre-procedure LGE-CMR. Retrospectively, scar characteristics were compared between patients with and without VT target sites in the SV. The ratio between SV-related scarring and the total cardiac scarring was defined as the SV scar index: SV-related scarring/total cardiac scarring. RESULTS: VT target sites were identified in the SV in 22 (51%) of 43 patients. LGE-CMR identified peri-aortic scarring involving the SV in 34 patients (79%). Scarring extended to the septum in 26 patients, involved the lateral basal wall in 4, and both areas in 13 patients. Scar volume within the SV was larger in patients with SV-VT targets (1.7 ± 0.9 cm3 vs. 0.7 ± 0.6 cm3; p < 0.0001) compared with other patients. A cutoff scar volume identifying SV-VT targets was 1.23 cm3 in the short-axis view (area under the curve 0.82; sensitivity 0.64; specificity 0.91). The SV scar index was significantly greater in patients who had SV-VT target sites (0.33 ± 0.2 vs. 0.09 ± 0.09; p < 0.0001). CONCLUSIONS: Patients with IDCM undergoing ablation of VT often have peri-aortic scarring visualized on LGE-CMR. Both the presence and the extent of scarring adjacent to the aortic annulus are associated with the presence of VT target sites within the SV.