Nonischemic or Dual Cardiomyopathy in Patients With Coronary Artery Disease.

BACKGROUND: Randomized trials in obstructive coronary artery disease (CAD) have largely shown no prognostic benefit from coronary revascularization. Although there are several potential reasons for the lack of benefit, an underexplored possible reason is the presence of coincidental nonischemic cardiomyopathy (NICM). We investigated the prevalence and prognostic significance of NICM in patients with CAD (CAD-NICM). METHODS: We conducted a registry study of consecutive patients with obstructive CAD on coronary angiography who underwent contrast-enhanced cardiovascular magnetic resonance imaging for the assessment of ventricular function and scar at 4 hospitals from 2004 to 2020. We identified the presence and cause of cardiomyopathy using cardiovascular magnetic resonance imaging and coronary angiography data, blinded to clinical outcomes. The primary outcome was a composite of all-cause death or heart failure hospitalization, and secondary outcomes were all-cause death, heart failure hospitalization, and cardiovascular death. RESULTS: Among 3023 patients (median age, 66 years; 76% men), 18.2% had no cardiomyopathy, 64.8% had ischemic cardiomyopathy (CAD+ICM), 9.3% had CAD+NICM, and 7.7% had dual cardiomyopathy (CAD+dualCM), defined as both ICM and NICM. Thus, 16.9% had CAD+NICM or dualCM. During a median follow-up of 4.8 years (interquartile range, 2.9, 7.6), 1116 patients experienced the primary outcome. In Cox multivariable analysis, CAD+NICM or dualCM was independently associated with a higher risk of the primary outcome compared with CAD+ICM (adjusted hazard ratio, 1.23 [95% CI, 1.06-1.43]; P=0.007) after adjustment for potential confounders. The risks of the secondary outcomes of all-cause death and heart failure hospitalization were also higher with CAD+NICM or dualCM (hazard ratio, 1.21 [95% CI, 1.02-1.43]; P=0.032; and hazard ratio, 1.37 [95% CI, 1.11-1.69]; P=0.003, respectively), whereas the risk of cardiovascular death did not differ from that of CAD+ICM (hazard ratio, 1.15 [95% CI, 0.89-1.48]; P=0.28). CONCLUSIONS: In patients with CAD referred for clinical cardiovascular magnetic resonance imaging, NICM or dualCM was identified in 1 of every 6 patients and was associated with worse long-term outcomes compared with ICM. In patients with obstructive CAD, coincidental NICM or dualCM may contribute to the lack of prognostic benefit from coronary revascularization.

Ventricular tachycardia ablation with pentaspline pulsed field technology in two patients with ischemic cardiomyopathy.

INTRODUCTION: Due to its unique features, pulsed field ablation (PFA) could potentially overcome some limitations of current radiofrequency (RF) ventricular tachycardia (VT) ablation. However, data on the use of PFA in this setting are currently scarce. METHODS: Two patients with ischemic cardiomyopathy and previously failed RF VT ablations were treated with PFA. RESULTS: A total of 18 bipolar applications (case1) and seven bipolar applications (case2) were delivered to the infero-lateral and infero-septal areas (case1) and to the apical lateral left ventricular (LV) wall (case2), placing the catheter adjacent to the LV wall in the flower configuration. A rapid cessation of VT and restoration of sinus rhythm were observed during PFA delivery in both cases. Further applications were delivered to achieve complete elimination of late potentials. In case 1, during the in-hospital stay, ECG monitoring did not show VT recurrences. Six-month follow-up was uneventful, with no VT recurrences at ICD interrogation. In case 2, due to postdischarge VT recurrences, a second RF procedure was scheduled 1 month later. The voltage map performed in sinus rhythm showed a low-voltage zone located at the anterolateral wall, near the previous ablation site. Numerous late potentials were recorded. At the 6-month follow-up, no further VT recurrences were documented after RF redo ablation. CONCLUSION: While the speed of application and potential transmural effect can facilitate the ablation of large diseased endocardial areas, early loss of contact due to difficult pentaspline catheter manipulation in the LV could lead to insufficient contact force and, consequently, inadequate energy penetration.

Ischemic cardiomyopathy: epidemiology, pathophysiology, outcomes, and therapeutic options.

Ischemic cardiomyopathy (ICM) is the most prevalent cause of heart failure (HF) in developed countries, with significant morbidity and mortality, despite constant improvements in the management of coronary artery disease. Current literature on this topic remains fragmented. Therefore, this review aimed to summarize the most recent data on ICM, focusing on its definition, epidemiology, outcomes, and therapeutic options. The most widely accepted definition is represented by a left ventricular dysfunction in the presence of significant coronary artery disease. The prevalence of ICM is largely influenced by age and sex, with older individuals and males being more affected. Its pathophysiology is characterized by plaque buildup, thrombus formation, hypoperfusion, ischemic cell death, and left ventricular remodeling. Despite improvements in therapy, ICM still represents a public health burden, with a 1-year mortality rate of 16% and a 5-year mortality rate of approximately 40% in the USA and Europe. Therefore, optimization of cardiovascular function, prevention of progressive remodeling, reduction of HF symptoms, and improved survival are the main goals of treatment. Therapeutic options for ICM include lifestyle changes, optimal medical therapy, revascularization, device therapy, mechanical circulatory support, and cardiac transplantation. Personalized management strategies and tailored patient care are needed to improve the outcomes of patients with ICM.

Type 1 diabetes, its complications, and non-ischemic cardiomyopathy: a mendelian randomization study of European ancestry.

BACKGROUND: Type 1 diabetes (T1D) is a significant risk factor for a range of cardiovascular diseases. Nonetheless, the causal relationship between T1D and non-ischemic cardiomyopathy (NICM) remains to be elucidated. Furthermore, the mechanisms responsible for the progression from T1D to NICM have not been definitively characterized. OBJECTIVE: The aim of this study was to conduct a Mendelian randomization (MR) study to investigate the causal effects of T1D and its complications on the development of NICM. Additionally, this study aimed to conduct a mediation analysis to identify potential mediators within this correlation. METHODS: Genetic variants were used as instrumental variables for T1D. The summary data for T1D were obtained from two genome-wide association study datasets. The summary data for T1D with complications and NICM were obtained from the Finnish database. Two-sample MR, multivariable MR and mediation MR were conducted in this study. RESULTS: The study revealed a causal association between T1D, T1D with complications, and NICM (with odds ratios of 1.02, 95% CI 1.01-1.04, p = 1.17e-04 and 1.03, 95% CI 1.01-1.05, p = 3.15e-3). Even after adjusting for confounding factors such as body mass index and hypertension, T1D remained statistically significant (with odds ratio of 1.02, 95% CI 1.01-1.04, p = 1.35e-4). Mediation analysis indicated that monokine induced by gamma interferon may play a mediating role in the pathogenesis of T1D-NICM (mediation effect indicated by odds ratio of 1.005, 95% CI 1.001-1.01, p = 4.9e-2). CONCLUSION: The study demonstrates a causal relationship between T1D, its complications, and NICM. Additionally, monokine induced by gamma interferon may act as a potential mediator in the pathogenesis of T1D-NICM.

20 years of treating ischemic cardiomyopathy with mesenchymal stromal cells: a meta-analysis and systematic review.

This meta-analysis and systematic review compiles comparative data from 2004 to 2024, investigating the safety and efficacy of mesenchymal stem/stromal cells (MSCs) derived from various tissues for the treatment of ischemic cardiomyopathy (ICM) and associated heart failure. In addition, this review highlights the limitations of these interventions and provides valuable insights for future therapeutic approaches. Relevant articles were retrieved from the PubMed® database using targeted keywords. Our inclusion criteria included clinical trials with patients over 18 years of age, case reports and pilot studies. Animal experiments, in vitro studies, correlational and longitudinal studies, and study designs and protocols were excluded. Forty-nine original articles resulted in follow-up reports of 45 trials. MSCs from bone marrow, umbilical cord and adipose tissue were moderately well tolerated. Of the 1408 participants who received MSCs, 33 trials (67.3%) reported the occurrence of death or serious adverse events. These events resulted in 80 deaths (52% of reported cases) following MSC administration. Importantly, 41.3% of these deaths (n = 33) were not considered to be related to the intervention itself, while 40% of these deaths had no reported cause. As the primary outcome, the mean increase in left ventricular ejection fraction (LVEF) from baseline was 5.75% (95% CI: 3.38% -8.11%, p < 0.0001, I2 = 90,9%) in the randomized controlled trials only (n = 24) within the treatment groups and 3.19% (95% CI: 1.63% to 4.75%, p < 0.0001, I2 = 74,17%) in the control groups after the intervention. When the above results were compared using the standardized mean difference (SDM), a significance in favor of the treatment group was also found (SDM = 0.41; 95% CI: 0.19-0.64, p < 0.001, I2 = 71%). Although improvements were also seen in the control groups, 33.3% (n = 15) of the studies showed no significant difference between the control and treatment groups. The 6-minute walking test (6MWT) and New York Heart Association (NYHA) class scores, used for assessing exercise tolerance and quality of life (QoL), respectively, further supported the improvements in the treatment group. These improvements were noted as 62.5% (n = 10) for the 6MWT and 54.5% (n = 12) for the NYHA class scores. According to the risk of bias analysis, 4 trials were of good quality (11.8%), 15 were of fair quality (44.1%), and 15 were of poor quality (44.1%). Major limitations of these studies included small sample size, diagnostic challenges/lack, uncertain cell dosage and potential bias in patient selection. Despite the ongoing debate surrounding cell administration for ICM, there are supporting signs of improved clinical and laboratory outcomes, as well as improved QoL in the MSC-treated groups. However, it is important to recognize the limitations of each study, highlighting the need for larger, controlled trials to validate these findings.

MRI Assessment of Myocardial Deformation for Risk Stratification of Major Arrhythmic Events in Patients With Non-Ischemic Cardiomyopathy Eligible for Primary Prevention Implantable Cardioverter Defibrillators.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) intervention is an established prophylactic measure. Identifying high-benefit patients poses challenges. PURPOSE: To assess the prognostic value of cardiac magnetic resonance imaging (MRI) parameters including myocardial deformation for risk stratification of ICD intervention in non-ischemic cardiomyopathy (NICM) while accounting for competing mortality risk. STUDY TYPE: Retrospective and prospective. POPULATION: One hundred and fifty-nine NICM patients eligible for primary ICD (117 male, 54 ± 13 years) and 49 control subjects (38 male, 53 ± 5 years). FIELD STRENGTH/SEQUENCE: Balanced steady state free precession (bSSFP) and three-dimensional phase-sensitive inversion-recovery late gadolinium enhancement (LGE) sequences at 1.5 T or 3 T. ASSESSMENT: Patients underwent MRI before ICD implantation and were followed up. Functional parameters, left ventricular global radial, circumferential and longitudinal strain, right ventricular free wall longitudinal strain (RV FWLS) and left atrial strain were measured (Circle, cvi42). LGE presence was assessed visually. The primary endpoint was appropriate ICD intervention. Models were developed to determine outcome, with and without accounting for competing risk (non-sudden cardiac death), and compared to a baseline model including LGE and clinical features. STATISTICAL TESTS: Wilcoxon non-parametric test, Cox's proportional hazards regression, Fine-Gray competing risk model, and cumulative incidence functions. Harrell's c statistic was used for model selection. A P value <0.05 was considered statistically significant. RESULTS: Follow-up duration was 1176 ± 960 days (median: 896). Twenty-six patients (16%) met the primary endpoint. RV FWLS demonstrated a significant difference between patients with and without events (-12.5% ± 5 vs. -16.4% ± 5.5). Univariable analyses showed LGE and RV FWLS were significantly associated with outcome (LGE: hazard ratio [HR] = 3.69, 95% CI = 1.28-10.62; RV FWLS: HR = 2.04, 95% CI = 1.30-3.22). RV FWLS significantly improved the prognostic value of baseline model and remained significant in multivariable analysis, accounting for competing risk (HR = 1.73, 95% CI = 1.12-2.66). DATA CONCLUSIONS: In NICM, RV FWLS may provide additional predictive value for predicting appropriate ICD intervention. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 5.

Long-term survival of ischemic cardiomyopathy patients with severe left ventricular dysfunction after CABG vs heart transplantation: A single center retrospective analysis.

BACKGROUND: There are no guidelines on the surgical management for ischemic cardiomyopathy (ICM) patients with severe left ventricular dysfunction. The present study aims to assess the long-term survival of these patients treated with two different surgical techniques, coronary artery bypass grafting (CABG) and heart transplantation (HTx). METHODS: This retrospective study included 218 ICM patients with left ventricular ejection fraction (LVEF) ≤35% who underwent CABG (n = 106) and HTx (n = 112) from 2011 to 2021 in a single center. After propensity adjustment analysis each group consisted of 51 patients. Clinical characteristics were evaluated for all-cause follow-up mortality by the Cox proportional hazards regression model. A risk prediction model was generated from multivariable-adjusted Cox regression analysis and applied to stratify patients with different clinical risks. The long-term survival was estimated by Kaplan-Meier analysis for different surgery groups. RESULTS: Long-term survival was comparable between CABG and HTx groups. After being stratified into different risk subgroups according to risk predictors, the HTx group exhibited superior survival outcomes compared to the CABG group among the high-risk patients (67.8% vs 44.4%, 64.1% vs 38.9%, and 64.1% vs 33.3%, p = 0.047) at 12, 36, and 60 months respectively, while the survival was comparable between HTx and CABG groups among low-risk patients (87.0% vs 97.0%, 82.4% vs 97.0%, and 70.2% vs 91.6%, p = 0.11) at 12, 36, and 60 months respectively in the PSM cohort. CONCLUSION: Long-term survival in ICM patients with severe left ventricular dysfunction who received CABG or HTx was comparable in general. Nonetheless, a favorable outcome of HTx surgery compared to CABG was observed among high-risk patients.

Society for Cardiovascular Magnetic Resonance 2023 Cases of SCMR Case Series.

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2023 digital collection of cases are presented in this manuscript.

Competency based curriculum for cardiovascular magnetic resonance: A position statement of the Society for Cardiovascular Magnetic Resonance.

This position statement guides cardiovascular magnetic resonance (CMR) imaging program directors and learners on the key competencies required for Level II and III CMR practitioners, whether trainees come from a radiology or cardiology background. This document is built upon existing curricula and was created and vetted by an international panel of cardiologists and radiologists on behalf of the Society for Cardiovascular Magnetic Resonance (SCMR).

Hemoglobin is an independent predictor of improvement exercise tolerance in male patients with non-ischemic cardiomyopathy.

Exercise intolerance is a symptom of chronic heart failure (CHF). The magnitude of exercise tolerance, as measured by peak oxygen uptake (peak VO2), is strongly associated with prognosis in patients with CHF. We aimed to evaluate the factors associated with improved exercise tolerance in patients with HF. In this prospective study, we recruited patients who were diagnosed with non-ischemic cardiomyopathy between September 2017 and September 2021. All patients underwent cardiopulmonary exercise testing at discharge and 6 months after enrollment. The patients were stratified according to whether peak VO2 was increased or not at 6 months. One hundred patients with a reduced left-ventricular ejection fraction (LVEF < 50%) were enrolled. Improvement of peak VO2 was observed in 74 patients. In male patients, hemoglobin level was higher in the increased peak VO2 group than in the non-increased group (15.0 ± 1.9 g/dL vs. 13.1 ± 2.1 g/dL; p < 0.01). Baseline hemoglobin level was positively correlated with the percentage change in peak VO2 (Spearman's r = 0.248, p = 0.040). Kaplan-Meier analysis demonstrated that adverse cardiac events were significantly less frequent in the increased peak VO2 group than in the non-increased group (log-rank test, p = 0.032). Multivariate logistic regression analysis identified hemoglobin level as an independent predictor of improved peak VO2 [odds ratio (OR) 1.60; 95% confidence interval (CI) 1.05-2.44; p = 0.027]. Baseline hemoglobin level is an independent predictor of improved peak VO2 in male patients with non-ischemic cardiomyopathy.

Combined use of frontal plane QRS-T angle and platelet-to-lymphocyte ratio in the risk prediction of ischemic cardiomyopathy in STEMI.

BACKGROUND: Frontal plane QRS-T angle (fQRS-T) and platelet-to-lymphocyte ratio (PLR) are highly important parameters that well-predict unfavorable outcomes in patients with ST-elevated myocardial infarction (STEMI).There are limited data on the predictive significance of ischemic cardiomyopathy (I-CMP) from the combination of fQRS-T and PLR in STEMI, compared to using fQRS-T and PLR alone. AIM: We aimed to evaluate the ability of the combination of fQRS-T and PLR routinely obtained on admission to identify STEMI patients at risk of I-CMP. METHOD: Six hundred and thirty-eight consecutive patients with STEMI who underwent primary percutaneous coronary intervention between 2018 and 2021 were included. The assessment of I-CMP was conducted through two-dimentional (2D)-echocardiography 6 weeks post-STEMI and I-CMP was defined as a left ventricular ejection fraction (LVEF) of 50% or less. Multivariate logistic regression analysis and receiver operating curve (ROC) analysis were performed to predict the development of I-CMP. RESULTS: In ROC analysis, the cut-off values of fQRS-T and PLR for best predicting I-CMP were 66.72° and 101.23, respectively. The model using the combination of two markers was the most powerful predictor of I-CMP risk (OR: 3.183, 95% CI: 1.971-5.139, p = .001) when included in a single variable such as high fQRS-T or high PLR (OR: 1.422, 95% CI: 0.870-0.232, p = .160). Additionally, the concomitant presence of high fQRS-T and high PLR exhibited the highest specificity (77%) for I-CMP relative to the individual presence of high fQRS-T (66%) or PLR (49%). CONCLUSION: The combination of fQRS-T and PLR, which is a simple and cost-effective risk assessment, may serve as a more reliable prognosticator for I-CMP as opposed to the use of fQRS-T and PLR alone for STEMI.

Programmatic approach to patients with advanced ischemic cardiomyopathy: Integrating microaxial support into strategies for the modern era.

Patients with advanced ischemic cardiomyopathy manifesting as left ventricular dysfunction exist along a spectrum of severity and risk, and thus decision-making surrounding optimal management is challenging. Treatment pathways can include medical therapy as well as revascularization through percutaneous coronary intervention or coronary artery bypass grafting. Additionally, temporary and durable mechanical circulatory support, as well as heart transplantation, may be optimal for select patients. Given this spectrum of risk and the complexity of treatment pathways, patients may not receive appropriate therapy given their perceived risk, which can lead to sub-satisfactory outcomes. In this review, we discuss the identification of high-risk ischemic cardiomyopathy patients, along with our programmatic approach to patient evaluation and perioperative optimization. We also discuss our strategies for therapeutic decision-making designed to optimize both short- and long-term patient outcomes.

Stem Cell Therapy against Ischemic Heart Disease.

Ischemic heart disease, which is one of the top killers worldwide, encompasses a series of heart problems stemming from a compromised coronary blood supply to the myocardium. The severity of the disease ranges from an unstable manifestation of ischemic symptoms, such as unstable angina, to myocardial death, that is, the immediate life-threatening condition of myocardial infarction. Even though patients may survive myocardial infarction, the resulting ischemia-reperfusion injury triggers a cascade of inflammatory reactions and oxidative stress that poses a significant threat to myocardial function following successful revascularization. Moreover, despite evidence suggesting the presence of cardiac stem cells, the fact that cardiomyocytes are terminally differentiated and cannot significantly regenerate after injury accounts for the subsequent progression to ischemic cardiomyopathy and ischemic heart failure, despite the current advancements in cardiac medicine. In the last two decades, researchers have realized the possibility of utilizing stem cell plasticity for therapeutic purposes. Indeed, stem cells of different origin, such as bone-marrow- and adipose-derived mesenchymal stem cells, circulation-derived progenitor cells, and induced pluripotent stem cells, have all been shown to play therapeutic roles in ischemic heart disease. In addition, the discovery of stem-cell-associated paracrine effects has triggered intense investigations into the actions of exosomes. Notwithstanding the seemingly promising outcomes from both experimental and clinical studies regarding the therapeutic use of stem cells against ischemic heart disease, positive results from fraud or false data interpretation need to be taken into consideration. The current review is aimed at overviewing the therapeutic application of stem cells in different categories of ischemic heart disease, including relevant experimental and clinical outcomes, as well as the proposed mechanisms underpinning such observations.

Harmony in Chaos: Deciphering the Influence of Ischemic Cardiomyopathy and Non-Cardiac Comorbidities on Holter ECG Parameters in Chronic Heart Failure Patients: A Pilot Study.

Background and Objective: In the landscape of heart failure, non-cardiac comorbidities represent a formidable challenge, imparting adverse prognostic implications. Holter ECG monitoring assumes a supplementary role in delineating myocardial susceptibility and autonomic nervous system dynamics. This study aims to explore the potential correlation between Holter ECG parameters and comorbidities in individuals with ischemic cardiomyopathy experiencing heart failure (HF), with a particular focus on the primary utility of these parameters as prognostic indicators. Materials and Methods: In this prospective inquiry, a cohort of 60 individuals diagnosed with heart failure underwent stratification into subgroups based on the presence of comorbidities, including diabetes, chronic kidney disease, obesity, or hyperuricemia. Upon admission, a thorough evaluation of all participants encompassed echocardiography, laboratory panel analysis, and 24 h Holter monitoring. Results: Significant associations were uncovered between diabetes and unconventional physiological indicators, specifically the Triangular index (p = 0.035) and deceleration capacity (p = 0.002). Pertaining to creatinine clearance, notable correlations surfaced with RMSSD (p = 0.026), PNN50 (p = 0.013), and high-frequency power (p = 0.026). An examination of uric acid levels and distinctive Holter ECG patterns unveiled statistical significance, particularly regarding the deceleration capacity (p = 0.045). Nevertheless, in the evaluation of the Body Mass Index, no statistically significant findings emerged concerning Holter ECG parameters. Conclusions: The identified statistical correlations between non-cardiac comorbidities and patterns elucidated in Holter ECG recordings underscore the heightened diagnostic utility of this investigative modality in the comprehensive evaluation of individuals grappling with HF. Furthermore, we underscore the critical importance of the thorough analysis of Holter ECG recordings, particularly with regard to subtle and emerging parameters that may be overlooked or insufficiently acknowledged.

[Prediction of myocardial contractility after coronary bypass surgery according to preoperative contrast-enhanced magnetic resonance imaging and echocardiography]. / Prognozirovanie dinamiki sokratitel'noi funktsii miokarda u patsientov posle koronarnogo shuntirovaniya po dannym predoperatsionnykh magnitno-rezonansnoi tomografii serdtsa s kontrastnym usileniem i ekhokardiografii.

OBJECTIVE: To establish the criteria for reversibility of myocardial contractility in patients with coronary artery disease (CAD) after coronary artery bypass grafting considering data of cardiac magnetic resonance imaging (MRI) and echocardiography. MATERIAL AND METHODS: We studied the results of coronary artery bypass grafting in 186 patients with CAD complicated by reduced left ventricular ejection fraction (<30%). All patients underwent cardiac MRI and echocardiography before surgery. Immediate and long-term results were evaluated according to echocardiography and MRI data. RESULTS: We confirmed the previously established predictors of improvement in left ventricular contractility: diastolic IVST ≥10.5 mm and PWT ≥9.5 mm, score of LV myocardium damage according to MRI with delayed contrast enhancement (p<0.05). Multivariate analysis makes it possible to calculate prognostic index and obtain information about further myocardial contractility after revascularization with an error of 6%. CONCLUSION: Echocardiography and contrast-enhanced cardiac MRI are valuable to assess morphological and functional state of the left ventricle in patients with ischemic cardiomyopathy and preoperatively determine functional reserve of the myocardium.

Defining the Sarcomeric Proteoform Landscape in Ischemic Cardiomyopathy by Top-Down Proteomics.

Ischemic cardiomyopathy (ICM) is a prominent form of heart failure, but the molecular mechanisms underlying ICM remain relatively understudied due to marked phenotypic heterogeneity. Alterations in post-translational modifications (PTMs) and isoform switches in sarcomeric proteins play important roles in cardiac pathophysiology. Thus, it is essential to define sarcomeric proteoform landscape to better understand ICM. Herein, we have implemented a top-down liquid chromatography (LC)-mass spectrometry (MS)-based proteomics method for the identification and quantification of sarcomeric proteoforms in the myocardia of donors without heart diseases (n = 16) compared to end-stage ICM patients (n = 16). Importantly, quantification of post-translational modifications (PTMs) and expression reveal significant changes in various sarcomeric proteins extracted from ICM tissues. Changes include altered phosphorylation and expression of cardiac troponin I (cTnI) and enigma homologue 2 (ENH2) as well as an increase in muscle LIM protein (MLP) and calsarcin-1 (Cal-1) phosphorylation in ICM hearts. Our results imply that the contractile apparatus of the sarcomere is severely dysregulated during ICM. Thus, this is the first study to uncover significant molecular changes to multiple sarcomeric proteins in the LV myocardia of the end-stage ICM patients using liquid chromatography-mass spectrometry (LC-MS)-based top-down proteomics. Raw data are available via the PRIDE repository with identifier PXD038066.

An effective disease diagnostic model related to pyroptosis in ischemic cardiomyopathy.

Pyroptosis is involved in ischemic cardiomyopathy (ICM). The study aimed to investigate the pyroptosis-related genes and clarify their diagnostic value in ICM. The bioinformatics method identified the differential pyroptosis genes between the normal control and ICM samples from online datasets. Then, protein-protein interaction (PPI) and function analysis were carried out to explore the function of these genes. Following, subtype analysis was performed using ConsensusClusterPlus, functions, immune score, stromal score, immune cell proportion and human leukocyte antigen (HLA) genes between subtypes were investigated. Moreover, optimal pyroptosis genes were selected using the least absolute shrinkage and selection operator (LASSO) analysis to construct a diagnostic model and evaluate its effectiveness using receiver operator characteristic (ROC) analysis. Twenty-one differential expressed pyroptosis genes were identified, and these genes were related to immune and pyroptosis. Subtype analysis identified two obvious subtypes: sub-1 and sub-2. And LASSO identified 13 optimal genes used to construct the diagnostic model. The diagnostic model in ICM diagnosis with the area under ROC (AUC) was 0.965. Our results suggested that pyroptosis was tightly associated with ICM.

A canine model of chronic ischemic heart failure.

Preclinical large animal models of chronic heart failure (HF) are crucial to both understanding pathological remodeling and translating fundamental discoveries into novel therapeutics for HF. Canine models of ischemic cardiomyopathy are historically limited by either high early mortality or failure to develop chronic heart failure. Twenty-nine healthy adult dogs (30 ± 4 kg, 15/29 male) underwent thoracotomy followed by one of three types of left anterior descending (LAD) coronary artery ligation procedures: group 1 (n = 4) (simple LAD: proximal and distal LAD ligation); group 2 (n = 14) (simple LAD plus lateral wall including ligation of the distal first diagonal and proximal first obtuse marginal); and group 3 (n = 11) (total LAD devascularization or TLD: simple LAD plus ligation of proximal LAD branches to both the right and left ventricles). Dogs were followed until chronic severe HF developed defined as left ventricular ejection fraction (LVEF) < 40% and NH2-terminal-prohormone B-type natriuretic peptide (NT-proBNP) > 900 pmol/L. Overall early survival (48-h postligation) in 29 dogs was 83% and the survival rate at postligation 5 wk was 69%. Groups 1 and 2 had 100% and 71% early survival, respectively, yet only a 50% success rate of developing chronic HF. Group 3 had excellent survival at postligation 48 h (91%) and a 100% success in the development of chronic ischemic HF. The TLD approach, which limits full LAD and collateral flow to its perfusion bed, provides excellent early survival and reliable development of chronic ischemic HF in canine hearts.NEW & NOTEWORTHY The novel total left anterior descending devascularization (TLD) approach in a canine ischemic heart failure model limits collateral flow in the ischemic zone and provides excellent early survival and repeatable development of chronic ischemic heart failure in the canine heart. This work provides a consistent large animal model for investigating heart failure mechanisms and testing novel therapeutics.

Development and validation of a novel nomogram to predict the impact of the polymorphism of the ICAM-1 gene on the prognosis of ischemic cardiomyopathy.

The current study investigated the association between polymorphisms of the ICAM-1 gene and prognosis of Ischemic cardiomyopathy (ICM), and developed a prognostic nomogram for ICM on the basis of ICAM-1 gene variants. The current study included totally 252 patients with ICM. In addition, PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used to genotype SNPs in the ICAM-1 gene in the patients. Later, the nomogram model was built by combining clinical data and ICAM-1 gene variants. This study used the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection into an ICM prognostic model. Furthermore, multivariate Cox-regression was applied to build the prognostic model, which included clinical and gene features chosen by the LASSO regression model. Following that, the receiver operating characteristic (ROC) curve, C-index, calibration plot analyses and decision curve analysis (DCA) were carried out to evaluate the discrimination ability, consistency, and clinical utility of the prognostic model, and the bootstrap method was adopted for internal validation. predicting factors rs112872667, treating by PCI or CABG, ventricular arrhythmia, left ventricular end-diastolic diameter (LVDD), use of ß-blockers, systolic blood pressure (SBP), heart rate (HR), and serum sodium were incorporated into the prognostic nomogram. The constructed nomogram performed well in discrimination ability, as observed by the time-dependent C-index. Furthermore, as shown by calibration curves, our nomogram's predicted probabilities were highly consistent with measured values. With threshold probabilities, DCA suggested that our nomogram could be useful in the clinic. mutation of rs112872667 have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC). Mutation of rs112872667 in ICAM-1 gene have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC).

Usefulness of the Vall d'Hebron Risk Score to stratify the risk of patients with ischemic cardiomyopathy.

BACKGROUND: To evaluate the Vall d'Hebron-Risk-Score (VH-RS) to stratify the risk of patients with stable ischemic cardiomyopathy (ICM), and assess whether hemoglobin (Hb) and estimated glomerular filtration rate (eGFR) provide additional information to the VH-RS. METHODS AND RESULTS: We analysed 673 consecutive patients with ICM who underwent gated SPECT. According to VH-RS, we stratified patients into 4-risk-levels: very-low-risk (VLR), low-risk (LR), moderate-risk (MR), and high-risk (HRi). We considered as MACEs: non-fatal myocardial infarction (MI), heart failure hospitalization (HF), coronary revascularization (CR), and cardiac death (CD). Also the cardiac-resynchronization-therapy (CRT), and the implantable-cardioverter-defibrillator (ICD) were investigated. During the follow-up (4.8 ± 2.7 years), 379 patients had MACEs (0.18/patient/year). There were no patients in VLR and LR. All patients were reclassified in 3-risk-levels (MRi = 48; HRi = 121; VHRi[very high risk] = 504). Most patients with MACEs were in VHRi level (test-for-trend: MACEs ≥ 1 without CRT/ICD, P < .001; combined non-fatal MI, CD and CR, P < .001; MACEs ≥ 1 with CRT/ICD, P < .001). The Hb and eGFR values do not properly improve the risk stratification obtained by the VH-RS (global-NRI[net-reclassification-improvement] was: (MACEs ≥ 1 without CRT/ICD: - 10.6%; non-fatal MI, CD and CR: - 9.08%; and MACEs ≥ 1 with CRT/ICD: - 8.85%). CONCLUSION: VH-RS is effective in evaluating risk of patients with stable ICM. In our population, adding Hb and eGFR variables do not improve the performance of the VH-RS.