Ischemic Cardiomyopathy Patients Research Articles

Pre- and Post-Procedural Cardiac Imaging (CT and MRI) in Electrophysiology: A Clinical Consensus Statement of the European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI) of the ESC.

Imaging using cardiac computed tomography (CT) or magnetic resonance imaging (MR) has become an important option for anatomic and substrate delineation in complex atrial and ventricular tachycardia (VT) ablation procedures. CT more common than MR has been used to detect procedure-associated complications like esophageal, cerebral and vascular injury. This clinical consensus statement summarizes the current knowledge of CT and MR to facilitate electrophysiological procedures, the current value of real-time integration of imaging-derived anatomy and substrate information during the procedure and the current role of CT and MR in diagnosing relevant procedure-related complications. Practical advice on potential advantages of one imaging modality over the other is discussed for patients with implanted cardiac rhythm devices as well as for planning, intraprocedural integration and post-interventional management in atrial fibrillation (AF) and VT ablation patients. Establishing a team of electrophysiologists and cardiac-imaging specialists working on specific details of imaging for complex ablation procedures is key. CMR can safely be performed in most patients with implanted active cardiac devices. Standard procedures for pre- and post-scanning management of the device and potential CMR-associated device-malfunctions need to be in place. In VT patients imaging - specifically MR - may help to determine scar location and mural distribution in ischemic and non-ischemic cardiomyopathy patients beyond evaluating the underlying structural heart disease. Future directions in imaging may include the ability to register multiple imaging modalities, novel high-resolution modalities but also refinements of imaging-guided ablation strategies are expected.

Efficacy of Catheter Ablation for Ventricular Tachycardia in Ischemic Cardiomyopathy Patients without an ICD Implantation

BackgroundImplantable cardioverter defibrillator (ICD) prevents sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM). Catheter ablation has been shown to effectively reduce ventricular tachycardia (VT) recurrence, yet its efficacy in patients without an ICD implantation remains uncertain. ObjectiveWe aimed to investigate the outcomes of ablation for VT in ICM patients without a backup ICD. MethodsICM patients received ablation for VT without an ICD implantation were included in this study. Ablation was guided by either activation mapping or substrate mapping. Endocardial ablation was the primary strategy; epicardial access was considered when endocardial ablation failed. The primary endpoint was VT recurrence during follow-up, with secondary endpoints including cardiovascular rehospitalization, all-cause mortality, and a composite of these events. ResultsA total of 114 patients were included, with the mean age of 58.2 ± 11.1 years, 102 of whom (89.5%) were male.Twelve patients (10.5%) underwent endo-epicardial ablation, while the rest received endocardial ablation. With a median follow-up of 53.8 months (24.8-84.2), VT recurred in 45 patients (39.5%), and 6 patients (5.3%) died, including 2 SCD cases. The recurrence rate of VT was significantly lower in patients undergoing endo-epicardial ablation compared to those with endocardial ablation only (8.3% vs 43.1%, Log-rank P = 0.032). After multivariate adjustment, epicardial ablation remained associated with a reduced risk of VT recurrence (hazard ratio: 0.14, 95% confidential interval: 0.02-0.98, P = 0.048). ConclusionICM patients undergoing VT ablation without a backup ICD experienced a notably low rate of arrhythmic death, with most recurrences proving non-lethal.

ForCEPSS—A framework for cardiac electrophysiology simulations standardization

Background and Objective:Simulation of cardiac electrophysiology (CEP) is an important research tool that is increasingly being adopted in industrial and clinical applications. Typical workflows for CEP simulation consist of a sequence of processing stages starting with building an anatomical model and then calibrating its electrophysiological properties to match observable data. While the calibration stages are common and generalizable, most CEP studies re-implement these steps in complex and highly variable workflows. This lack of standardization renders the execution of computational CEP studies in an efficient, robust, and reproducible manner a significant challenge. Here, we propose ForCEPSS as an efficient and robust, yet flexible, software framework for standardizing CEP simulation studies. Methods and Results:Key processing stages of CEP simulation studies are identified and implemented in a standardized workflow that builds on openCARP11https://opencarp.org/. Plank et al. (2021) and the Python-based carputils22https://git.opencarp.org/openCARP/carputils. framework. Stages include (i) the definition and initialization of action potential phenotypes, (ii) the tissue scale calibration of conduction properties, (iii) the functional initialization to approximate a limit cycle corresponding to the dynamic reference state according to an experimental protocol, and, (iv) the execution of the CEP study where the electrophysiological response to a perturbation of the limit cycle is probed. As an exemplar application, we employ ForCEPSS to prepare a CEP study according to the Virtual Arrhythmia Risk Prediction protocol used for investigating the arrhythmogenic risk of developing infarct-related ventricular tachycardia (VT) in ischemic cardiomyopathy patients. We demonstrate that ForCEPSS enables a fully automated execution of all stages of this complex protocol. Conclusion:ForCEPSS offers a novel comprehensive, standardized, and automated CEP simulation workflow. The high degree of automation accelerates the execution of CEP simulation studies, reduces errors, improves robustness, and makes CEP studies reproducible. Verification of simulation studies within the CEP modeling community is thus possible. As such, ForCEPSS makes an important contribution towards increasing transparency, standardization, and reproducibility of in silico CEP experiments.

Impact of preventive substrate catheter ablation on implantable cardioverter-defibrillator interventions in patients with ischaemic cardiomyopathy and infarct-related coronary chronic total occlusion.

Primary prevention patients with ischaemic cardiomyopathy and chronic total occlusion of an infarct-related coronary artery (CTO) are at a particularly high risk of implantable cardioverter-defibrillator (ICD) therapy occurrence. The trial was designed to evaluate the efficacy of preventive CTO-related substrate ablation strategy in ischaemic cardiomyopathy patients undergoing primary prevention ICD implantation. The PREVENTIVE VT study was a prospective, multicentre, randomized trial including ischaemic patients with ejection fraction ≤40%, no documented ventricular arrhythmias (VAs), and evidence of scar related to the coronary CTO. Patients were randomly assigned 1:1 to a preventive substrate ablation before ICD implantation or standard therapy with ICD implantation only. The primary outcome was a composite of appropriate ICD therapy or unplanned hospitalization for VAs. Secondary outcomes included the primary outcome's components, the incidence of appropriate ICD therapies, cardiac hospitalization, electrical storm, and cardiovascular (CV) mortality. Sixty patients were included in the study. During the mean follow-up of 44.7 ± 20.7 months, the primary outcome occurred in 5 (16.7%) patients undergoing preventive substrate ablation and in 13 (43.3%) patients receiving only ICD [hazard ratio (HR): 0.33; 95% confidence interval (CI): 0.12-0.94; P = 0.037]. Patients in the preventive ablation group also had fewer appropriate ICD therapies (P = 0.039) and the electrical storms (Log-rank: P = 0.01). While preventive ablation also reduced cardiac hospitalizations (P = 0.006), it had no significant impact on CV mortality (P = 0.151). Preventive ablation of the coronary CTO-related substrate in patients undergoing primary ICD implantation is associated with the reduced risk of appropriate ICD therapy or unplanned hospitalization due to VAs.

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

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

Cine-cardiac magnetic resonance to distinguish between ischemic and non-ischemic cardiomyopathies: a machine learning approach.

This work aimed to derive a machine learning (ML) model for the differentiation between ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) on non-contrast cardiovascular magnetic resonance (CMR). This retrospective study evaluated CMR scans of 107 consecutive patients (49 ICM, 58 NICM), including atrial and ventricular strain parameters. We used these data to compare an explainable tree-based gradient boosting additive model with four traditional ML models for the differentiation of ICM and NICM. The models were trained and internally validated with repeated cross-validation according to discrimination and calibration. Furthermore, we examined important variables for distinguishing between ICM and NICM. A total of 107 patients and 38 variables were available for the analysis. Of those, 49 were ICM (34 males, mean age 60 ± 9years) and 58 patients were NICM (38 males, mean age 56 ± 19years). After 10 repetitions of the tenfold cross-validation, the proposed model achieved the highest area under curve (0.82, 95% CI [0.47-1.00]) and lowest Brier score (0.19, 95% CI [0.13-0.27]), showing competitive diagnostic accuracy and calibration. At the Youden's index, sensitivity was 0.72 (95% CI [0.68-0.76]), the highest of all. Analysis of predictions revealed that both atrial and ventricular strain CMR parameters were important for the identification of ICM patients. The current study demonstrated that using a ML model, multi chamber myocardial strain, and function on non-contrast CMR parameters enables the discrimination between ICM and NICM with competitive diagnostic accuracy. A machine learning model based on non-contrast cardiovascular magnetic resonance parameters may discriminate between ischemic and non-ischemic cardiomyopathy enabling wider access to cardiovascular magnetic resonance examinations with lower costs and faster imaging acquisition. • The exponential growth in cardiovascular magnetic resonance examinations may require faster and more cost-effective protocols. • Artificial intelligence models can be utilized to distinguish between ischemic and non-ischemic etiologies. • Machine learning using non-contrast CMR parameters can effectively distinguish between ischemic and non-ischemic cardiomyopathies.

Alterations in Mitochondrial Oxidative Phosphorylation System: Relationship of Complex V and Cardiac Dysfunction in Human Heart Failure.

Heart failure (HF) is a disease related to bioenergetic mitochondrial abnormalities. However, the whole status of molecules involved in the oxidative phosphorylation system (OXPHOS) is unknown. Therefore, we analyzed the OXPHOS transcriptome of human cardiac tissue by RNA-seq analyses (mRNA n = 36; ncRNA n = 30) in HF patients (ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM)) and control subjects. We detected 28 altered genes in these patients, highlighting greater deregulation in ICM. Specifically, we found a general overexpression of complex V (ATP synthase) elements, among them, ATP5I (ICM, FC = 2.04; p < 0.01), ATP5MJ (ICM, FC = 1.33, p < 0.05), and ATP5IF1 (ICM, FC = 1.81; p < 0.001), which presented a significant correlation with established echocardiographic parameters of cardiac remodeling and ventricular function as follows: left ventricular end-systolic (p < 0.01) and end-diastolic (p < 0.01) diameters, and ejection fraction (p < 0.05). We also detected an increase in ATP5IF1 protein levels (ICM, FC = 1.75; p < 0.01) and alterations in the microRNA expression levels of miR-208b-3p (ICM, FC = -1.44, p < 0.001), miR-483-3p (ICM, FC = 1.37, p < 0.01), regulators of ATP5I. Therefore, we observed the deregulation of the OXPHOS transcriptome in ICM patients, highlighting the overexpression of complex V and its relationship with cardiac remodeling and function.

Area-weighted unipolar voltage to predict heart failure outcomes in patients with ischaemic cardiomyopathy and ventricular tachycardia.

Patients with ischaemic cardiomyopathy (ICM) referred for catheter ablation of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodelling. Local unipolar voltages (UV) decrease with loss of viable myocardium. A UV parameter reflecting global viable myocardium may predict prognosis. We evaluate if a newly proposed parameter, area-weighted unipolar voltage (awUV), can predict HF-related outcomes [HFO; HF death/left ventricular (LV) assist device/heart transplant] in ICM. From endocardial voltage maps of consecutive patients with ICM referred for VT ablation, awUV was calculated by weighted interpolation of local UV. Associations between clinical and mapping parameters and HFO were evaluated and validated in a second cohort. The derivation cohort consisted of 90 patients [age 68 ±8 years; LV ejection fraction (LVEF) 35% interquartile range (IQR) (24-40)] and validation cohort of 60 patients [age 67 ± 9, LVEF 39% IQR (29-45)]. In the derivation cohort, during a median follow-up of 45 months [IQR (34-83)], 36 (43%) patients died and 23 (26%) had HFO. Patients with HFO had lower awUV [4.51 IQR (3.69-5.31) vs. 7.03 IQR (6.08-9.2), P < 0.001]. A reduction in awUV [optimal awUV (5.58) cut-off determined by receiver operating characteristics analysis] was a strong predictor of HFO (3-year HFO survival 97% vs. 57%). The cut-off value was confirmed in the validation cohort (2-year HFO-free survival 96% vs. 60%). The newly proposed parameter awUV, easily available from routine voltage mapping, may be useful at identifying ICM patients at high risk for HFO.

Temporal Trend in Revascularization for Patients With Ischemic Cardiomyopathy and Multivessel Coronary Artery Disease.

Current guidelines recommend revascularization in patients with ischemic cardiomyopathy (ICM). However, there is limited information about the trends and outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in ischemic cardiomyopathy patients with multivessel coronary artery disease. Using New Jersey state mandatory registries, 8083 patients with ischemic cardiomyopathy with CABG or PCI revascularization for multivessel coronary artery disease from 2007 to 2018 were included in the analysis. Joinpoint regression and multivariable logistic regression analyses were performed to assess the annual percentage change in trends and predictors of the 30-day mortality rate, respectively. A decline in CABG procedures was observed from 2007 to 2011 (annual percentage change, -11.5%; P=0.003), followed by stabilization. The PCI trend remained unchanged from 2007 to 2010 and then increased significantly (annual percentage change, 3.2%; P=0.02). In the subsample of patients with proximal left anterior descending artery plus circumflex and right coronary artery, CABG was a predominant procedure until 2011, and the proportion of both procedures did not differ thereafter. In the subsample of patients with left anterior descending artery and any other artery stenosis, PCI remained dominant from 2007 to 2018, while in patients with left main and any other artery stenosis, CABG remained dominant from 2007 to 2018 (P<0.001). The 30-day risk-adjusted mortality rate was higher after PCI versus CABG for each year, but after adjustment for completeness of revascularization, there was no difference between groups. The patterns of revascularization procedures for patients with ischemic cardiomyopathy with multivessel coronary artery disease have changed over the years, as evidenced by the changes in CABG and PCI trends. CABG and PCI had comparable 30-day risk-adjusted mortality risks.

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

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). 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. 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. 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.

VT ablation based on CT imaging substrate visualization: results from a large cohort of ischemic and non-ischemic cardiomyopathy patients.

The eradication of ventricular tachycardia (VT) isthmus sites constitutes the minimal procedural endpoint for VT ablation procedures. Contemporary high-resolution computed tomography (CT) imaging, in combination with computer-assisted analysis and segmentation of CT data, facilitates targeted elimination of VT isthmi. In this context, inHEART offers digitally rendered three-dimensional (3D) cardiac models which allow preoperative planning for VT ablations in ischemic and non-ischemic cardiomyopathies. To date, almost no data have been collected to compare the outcomes of VT ablations utilizing inHEART with those of traditional ablation approaches. The presented data are derived from a retrospective analysis of n = 108 patients, with one cohort undergoing VT ablation aided by late-enhancement CT and subsequent analysis and segmentation by inHEART, while the other cohort received ablation through conventional methods like substrate mapping and activation mapping. The ablations were executed utilizing a 3D mapping system (Carto3), with the mapping generated via the CARTO® PENTARAY™ NAV catheter and subsequently merged with the inHEART model, if available. Results showed more successful outcome of ablations for the inHEART group with lower VT recurrence (27% vs. 42%, p < 0.06). Subsequent analyses revealed that patients with ischemic cardiomyopathies appeared to derive a significant benefit from inHEART-assisted VT ablation procedures, with a higher rate of successful ablation (p = 0.05). Our findings indicate that inHEART-guided ablation is associated with reduced VT recurrence compared to conventional procedures. This suggests that employing advanced imaging and computational modeling in VT ablation may be valuable for VT recurrences.

Prediction of left ventricular ejection fraction improvement in patients with ischemic cardiomyopathy after coronary artery bypass grafting based on cardiac magnetic resonance.

To investigate the risk factors of left ventricular ejection fraction (LVEF) improvement in patients with ischemic cardiomyopathy (ICM) after coronary artery bypass grafting (CABG), and to construct a model that predicts LVEF improvement. A retrospective analysis was performed on 106 ICM patients who received CABG and underwent cardiac magnetic resonance (CMR) at Beijing Anzhen Hospital, Capital Medical University from January 2017 to June 2022. Patients were divided into two groups with improved LVEF and no improved LVEF based on the results of postoperative 6-month transthoracic echocardiography. To analyze the risk factors affecting the LVEF non-improvement after CABG and establish a prediction model. There was LVEF non-improvement in 30.2% (32/106) of patients. Multivariate analysis showed that the number of transmural scar segments and left ventricular end-systolic volume index (LVESVI) were independent risk factors in LVEF non-improvement after CABG [odds ratio (OR) =2.398, 95% confidence interval (CI): 1.607-3.579, P<0.001; OR =1.036, 95% CI: 1.009-1.063, P=0.008]. The model is built and internally verified. ROC showed that the area under the curve (AUC) was 0.866 (95% CI: 0.792-0.940), calibration curve showed that the probability predicted by the model matched well with the clinical results, and decision curve analysis (DCA) showed that the model had good clinical applicability. During the mean follow-up time of 1.5 years, the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) in the LVEF non-improvement group was higher (5.4% vs. 25.0%, P=0.009), and the NYHA grading was higher (P=0.016), when compared to the LVEF improvement group. The prediction model based on the number of transmural scar segments and LVESVI has good diagnostic efficacy. Our findings help to identify patients with improved LVEF and thus guide the selection of clinical treatment strategies.

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.

Disturbance of iron metabolism related genes in advanced heart failure

Abstract Background/Introduction Heart failure (HF) is a clinical syndrome associated with poor quality of life, substantial health-care resource utilization, and premature mortality. Iron is a nutrient required in all organ systems for various metabolic processes, such as mitochondrial function, oxygen transport, myocardial and skeletal muscle metabolism, among others. Maintaining iron homeostasis is essential for proper cardiac function since both iron deficiency and iron overload are associated with HF through complex mechanisms, such as ferroptosis. Purpose The aim of this study was to analyse the status of iron metabolism in hearts from patients with dilated (DCM) and ischemic cardiomyopathy (ICM) and its implication with the pathophysiology of the disease. Methods Cardiac tissue samples were used to evaluated transcriptome differences in genes involved iron metabolism by mRNA-sequencing (mRNA-seq; ICM, n=13; DCM, n=13; CNT, n=10). Furthermore, the miRNA implicated in the mRNA posttrasciptional regulation was studied through non-coding RNA-seq (ICM, n=22; DCM, n=20; CNT, n=8). Results We observed a decrease in iron import with SNX4 underexpression in ICM (FC=-1.28) and DCM (FC=-1.27) patients, p&amp;lt;0.05. While the export is reduced only in patients with MCD: HAMP is underexpresed (FC=-2.41, p&amp;lt;0.01) and its miRNA, miR-184, overexpressed (FC=2.77, p&amp;lt;0.01). We also found alterations in molecules of iron homeostasis and transporters of both aetiologies: IREB2 (ICM, FC=-1.27, p&amp;lt;0.05; DCM, FC=-1.48, p&amp;lt;0.001), STEAP3 (ICM, FC=-1.63, p&amp;lt;0.05; DCM, FC=-2.24, p&amp;lt;0.001), NOX4 (DCM, FC=1.70, p&amp;lt;0.05), SLC39A14 (ICM, FC=-1.97, p&amp;lt;0.05) and SLC39A8(ICM, FC=-1.60, p&amp;lt;0.05; DCM, FC=-1.78, p&amp;lt;0.01). Myoglobin was increased (FC=1.18, p&amp;lt;0.05) and its miRNA, miR-133a-3p, decreased (FC=-1.39, p&amp;lt;0.05) in DCM patients. While other molecules implicated in iron metabolism such as NFE2L2 (ICM, FC=-1.52; DCM, FC=-1.30; p&amp;lt;0.05) and AGPAT5 (ICM, FC=-1.84, p&amp;lt;0.05) are decreased. It is worth noting the correlation with ventricular dysfunction shown by SLC39A8 (end systolic diameter, r=-0.674; end diastolic diameter, r=-0.648; p&amp;lt;0.05) in ICM patients and NFE2L2 (ejection fraction, r=0.609, p&amp;lt;0.05) in DCM patients. Conclusions Our results show an alteration in the iron metabolism specific of aetiology in HF, both in the genes involved in different functions of the pathway and in its post-translational regulation. These results offer new possible therapeutic targets and valuable information to elucidate the complex mechanisms that relate iron homeostasis to HF.

Cardiac magnetic resonance for prophylactic implantable-cardioVerter defibrillator therapy international registry in patients with ischemic cardiomyopathy

Abstract Background Sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) remains a leading cause of death. Current guidelines provide a class I recommendation for implantable cardioverter–defibrillator (ICD) implantation in ICM patients with transthoracic echocardiographic (TTE) left ventricular ejection fraction (LVEF) ≤35%. and NYHA functional class II or III. The current paradigm is suboptimal in identifying patients who are likely to benefit. In fact, only a relatively small proportion of ICD recipients for SCD primary prevention receive appropriate device therapy and instead there is a not negligible percentage of patients who experienced SCD event despite not fulfilling criteria for implantation. Purpose The DERIVATE-ICM registry sought to evaluate the additional prognostic value for the indication of ICD implantation using cardiac magnetic resonance (CMR) as compared to standard of care based on TTE in a large cohort of ICM patients. Methods We enrolled 861 ICM patients (86% male, mean age 65±11 years) with chronic heart failure and TTE-LVEF&amp;lt;50%. Major adverse arrhythmic cardiac events (MAACE), defined as the combination of SCD, aborted SCD event, and sustained ventricular tachycardia. were the primary endpoint. Independent predictors were used to calculate a CMR risk score for each patient. Risk levels were defined as low (quantile 1 [Q1]), medium (Q2 and Q3) and high (Q4). Results During a median follow-up of 1054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR:1.007, 95%CI:1.000-1.011, p=0.05), CMR-LVEF (HR:0.972, 95%CI: 0.945-0.999, p=0.045) and late gadolinium enhancement (LGE) mass (HR:1.010, 95%CI: 1.002–1.018, p=0.015) were independent predictors of MAACE. Based on the multivariate analysis, CMR weighted risk score was developed according to the following equation [0.005 * EDV/BSA (mL/m2) – 0.029 * LVEF (%) + 0.010 * LGE ischemic mass (g)]. A multiparametric CMR weighted predictive derived score effectively identifies subjects at high risk for MAACE as compared to TTE-LVEF cut-off of 35% with a Continuous NRI: 31.7% (95%CI: 8.6%-54.8%, p=0.007) (Figure 1, Figure 2). Conclusions In this large multicenter registry, a multi-parametric CMR predictive model provides additional prognostic stratification for MAACE predictions in a large cohort of ICM patients as compared to standard of care. This model identifies a large number of patients with TTE-LVEF&amp;lt;35% at low risk of SCD event and on the other side it identifies a subset of patients who are at high risk of MAACE despite TTE-LVEF≥35% (i.e. the population currently not fulfilling the guideline-based criteria for ICD implantation). Further randomized trials to test a CMR guided strategy for ICD implantation versus standard of care are now needed.Kaplan-Meier curvesEvent rate redistribution

Incidence of sustained ventricular tachyarrhythmias in patients with non-ischemic cardiomyopathy in a multicenter multinational WCD cohort

Abstract Background Defibrillator use in patients with non-ischemic cardiomyopathy (NICM) and HFrEF remains controversial after the DANISH study. The new ESC guidelines recommend individualized risk stratification in these patients. The wearable cardioverter-defibrillator (WCD) seems to be appropriate to both protect and screen patients with HFrEF at risk for sudden cardiac death (SCD). Puropose: To evaluate the rate of ventricular tachyarrhythmias (VT/VF) in NICM vs. ICM patients receiving a WCD for temporary SCD protection. Methods 1157 patients were included in a multicenter registry from eight European centers. Among these patients, 602 patients received a WCD due to ischemic cardiomyopathy (ICM) and 555 patients for non-ischemic cardiomyopathy (NICM). Incidence of VT/VF and/or appropriate WCD shock discharge during WCD use were evaluated. The mean follow-up (FU) time of the whole cohort was 620.2±607.8 days. Results NICM patients were younger (mean 56.5±14.8a vs 63.9±11.6a; p&amp;lt;0.001) and less often male (75% vs. 87.2%; p&amp;lt;0.001) compared to ICM patients. Heart failure medication at hospital discharge did not differ between the two groups except for a higher prescription rate of aldosterone-antagonists in NICM compared to ICM patients (73.8% vs. 66.7%; p=0.02). The index left ventricular ejection fraction (LVEF) was significantly lower in NICM compared to ICM patients (mean 26.1±9.1% versus 29.5±9.2%; p&amp;lt;0.001). A larger extent of LVEF recovery was detected in NICM patients compared to ICM patients up to the end of WCD use (mean LVEF post WCD: 45.7±35.4% vs. 40.2±11.8%; p=0.02). Average daily WCD wear-time was significantly lower in NICM patients compared to ICM patients (mean 20.7±4.9h vs. 21.6±3.7h; p=0.01). NICM patients had a significantly lower incidence of sustained ventricular tachyarrhythmia (VT/VF) compared to ICM patients (3.4% vs. 6.6%; p=0.02). Consistently, rate of appropriate WCD shock was significantly lower in NICM vs. ICM patients (0.7% vs. 3.7%; p&amp;lt; 0.001), as was rate of re-hospitalization (30.2% vs. 46.1%; p&amp;lt;0.001). Both groups showed a similar mortality rate during FU. Conclusions Patients at risk for SCD with NICM showed a more pronounced LVEF recovery, significantly lower incidence of VT/VF with concomitant shocks and hospitalization, while overall mortality was unchanged compared to ICM patients. These results indicate that WCD use might facilitate individual SCD risk stratification in NICM patients.

Incremental prognostic value of late gadolinium enhancement extent, transmurality, and pattern in patients with ischaemic cardiomyopathy

Abstract Background Presence and extent of late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) are strong prognosticators of outcomes in ischaemic cardiomyopathy (ICM), but the prognostic value of multiple location of LGE, LGE transmurality, and midwall LGE area in addition to ischaemic LGE is not well established. Purpose To assess the incremental prognostic value of presence, extent, transmurality, and pattern of LGE in patients with ICM and reduced left ventricular ejection fraction (LVEF)­­. Methods Between 2008 and 2022, all consecutive patients referred for myocardial viability assessment using CMR and a history of ICM (≥70% stenosis in ≥1 epicardial coronary vessel on angiography and/or history of myocardial infarction and/or coronary revascularization) and LVEF value &amp;lt;50% were prospectively recruited. The outcome was all-cause death using the electronic French National Registry of Death. Nested Cox proportional hazard models were used to assess the prognostic value of the following LGE features: the extent, the transmurality of subendocardial ischaemic LGE (&amp;lt;50%, ≥50%, or transmural), the presence of LGE in multiple areas, and the presence of midwall LGE. The additional predictive value of the LGE features was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 6,082 included patients (mean age 65±12 years, 73% male, mean LVEF 43.8±5.7%), 3,591 (59%) had ischaemic LGE; 652 (10.7%) patients died during a median follow up of 9 [6.6-11.5] years. After adjustment for risk factors in the overall population, the presence of ischaemic LGE was associated with a higher risk of death (adjusted HR=3.57; 95%CI: 2.89-4.40, p&amp;lt;0.001). Figure 1 shows survival according to the different LGE features. Patients with both multiple localisations of ischaemic LGE area and additional LGE midwall exhibited the highest risk of death (p&amp;lt;0.001). After adjustment in the subgroup of patients with ischaemic LGE (n=3,591), LGE extent (HR=1.55; 95%CI: 1.47-1.63), multiple localisations of ischaemic LGE (HR 1.61 95%CI: 1.32-1.97), LGE transmurality (HR=4.48; 95%CI: 3.39-5.93), and presence of additional midwall LGE (HR=1.77; 95%CI: 1.44-2.17, all p&amp;lt;0.001) were independently associated with a higher risk of death. A model combining all LGE features showed the best improvement in model discrimination and reclassification above traditional factors (C-statistic improvement: 0.17; NRI=54.1%; IDI=12.6%, Chi-2 global=1133, all p&amp;lt;0.001; LR-test p&amp;lt;0.001, Figure 2). Conclusion In a large cohort of ICM patients with reduced LVEF, ischaemic LGE extent, transmurality, multiple ischaemic LGE localisations, and additional presence of midwall LGE were independent prognosticators of death. A model combining all these LGE features had an incremental prognostic value over traditional prognostic factors to predict all-cause death.Kaplan-Meier survival curvesIncremental prognostic value

Abstract 12761: Pathogenic Genetic Variants in Patients With Heart Transplant Due to Ischemic and Non-Ischemic Cardiomyopathy

Introduction: Current clinical guidelines recommend offering genetic testing to all patients diagnosed with non-ischemic cardiomyopathy (NICM), particularly in patients with a strong family history. The utility of genetic testing more broadly in patients with end-stage heart failure requiring heart transplant (HT) is unknown. Hypothesis: Among patients with HT, prevalence of cardiovascular disease (CVD)-associated pathogenic/likely pathogenic (P/LP) variants is higher in those with NICM than those with ischemic cardiomyopathy (ICM). Methods: We performed targeted DNA sequencing of 120 mendelian CVD genes in 124 consented patients with a HT, enrolled in the Vanderbilt Cardiac Catheterization Lab Cohort between 2003 and 2021. DNA sequence variation was annotated as P/LP based on ACMG criteria. Results: Out of 124 participants with HT, 70 had NICM and 51 had ICM. 22.8% of the NICM group harbored a P/LP variant in TTN (n=5), LMNA (5), MYH7 (1), RYR2 (1), RBM20 (1), COL1A2 (1), PKP2 (1), and CASQ2 (1). 19.6% of ICM participants harbored a P/LP variant in LDLR (2), RYR2 (1), TTN (1), SDHA (1), MYH7 (1), SGCD (1), MYL3 (1), CASQ2 (1), and COL1A2 (1). In NICM and ICM patients with a P/LP variant, 94% and 100% had a family history of CVD, respectively. By comparison in those without a P/LP variant, 59% and 73% had a family history of CVD. Out of 124 patients, only 13 had genetic testing through their clinical care, all of which occurred post-transplantation. 5/13 of these patients had a P/LP variant. Conclusions: This retrospective study showed a significant yield of genetic testing in HT patients. Notably, the overall prevalence of P/LP variants was nearly identical between NICM and ICM patients, with a higher rate of CM-related variants in the NICM group. We suggest that a genotype-first approach of screening all HT patients for genetic mutations enables earlier identification of actionable variants in HT probands and their family members than the current phenotype-guided approach.

Abstract 15327: Clinical Outcomes of Methamphetamine-Associated Cardiomyopathy Compared to Ischemic Cardiomyopathy: A Single Institution Retrospective Longitudinal Study

Background: Methamphetamine-associated cardiomyopathy (MAC) leads to significant morbidity and mortality. The benefit of implantable cardioverter-defibrillator (ICD) in this population is poorly characterized. Aims: To evaluate ICD use and outcomes in patients with MAC compared to ischemic cardiomyopathy (ICM). Methods: Electronic health record (EHR) was queried for all heart failure hospitalizations using ICD-9 codes between 2011 and 2019. Patients with an EF ≤ 35% were included. The MAC cohort was derived from this population and defined by ICD-9 code or positive urine toxicology and compared to ICM cohort. Baseline characteristics and outcomes were extracted from the EHR. MACE was defined as death, ventricular tachycardia, cardiac arrest, rehospitalization, atrial fibrillation (AF) or stroke. Results: The study included 294 patients in the MAC group and 373 patients in the ICM group. MAC patients were younger (56 vs 61 years, p&lt;0.001) compared to ICM (table 1). Readmission rates for heart failure at one year were similar (13% vs 11.2%, p=ns). Significantly fewer patients with MAC had ICD for primary prevention (15.0% vs 27.9%, p&lt;0.001). Mortality and AF were lower in MAC compared to ICM, however VT (2.38% vs 5.09%, p=0.072) and cardiac arrest (6.1% vs 7.8%, p=0.408) were similar between the two groups. MACE outcomes were worse in the ICM cohort (38.3% vs 21.1%, p=0.012) than MAC. In the MAC cohort, ICD presence was associated with 56.82% incidence of MACE compared to 40.00% without ICD (OR = 1.97, CI 1.032-3.77, p = 0.040) mainly due to higher AF hospitalization (22% vs 8%, p=0.01). Conclusion: ICM patients had higher mortality and atrial fibrillation compared to MAC. ICD implantation for primary prevention was not associated with reduced mortality, however this cohort had higher AF hospitalization. We need further studies to assess the benefit of ICD in MAC.

Abstract 16938: Epicardial Adipose Tissue on the Risk of Lethal Ventricular Arrhythmias in Patients With Nonischemic Cardiomyopathy Receiving Implantable Cardioverter-Defibrillator

Background: The arrhythmic risk stratification in patients with nonischemic cardiomyopathy (NICM) remains challenging. The implication of epicardial adipose tissue (EAT) on incident sudden cardiac death (SCD) is unclear. Objectives: To assess the relationship between EAT and SCD in NICM patients receiving implantable cardioverter-defibrillators (ICD) and compare this risk to patients with ischemic cardiomyopathy (ICM). Methods: A total of 421 patients scheduled for primary or secondary prevention ICD implantation underwent CMR at 1.5 or 3T, including cine and late gadolinium enhancement (LGE) imaging. EAT volume surrounding both ventricles was quantified with manual delineation on cine short-axis images and calculated by summation of EAT volume of each slice using the modified Simpson rule. LGE was semiautomatically quantified by adjusting a grayscale threshold. The primary endpoint was a composite of ICD therapy, including anti-tachycardia pacing and SCD. Results: We identified 265 NICM patients (mean age 54 years, 73% men), with LGE present in 152 patients (57%), including 85 patients (32%) with secondary prevention ICD. During the median follow-up of 2.9 years, 42 patients (16%) experienced the endpoint. Low EAT was associated with an increased risk of SCD in NICM patients (HR ad per 10ml decrease, 1.54; 95%CI, 1.19-1.96, p&lt;0.001), even after adjustment for other relevant disease variables. A continuous relationship was evident between EAT and subsequent ICD therapies (p=0.001). Even when considering 85 patients with secondary prevention ICD as theoretically having an SCD event, the risk of EAT in predicting SCD remained essentially unchanged. In contrast, EAT was not associated with increased SCD risk in ICM patients. Conclusions: Low EAT was associated with increased SCD risk in NICM patients receiving ICD implantation, especially primary prevention ICD. These data suggest a potential role of EAT in identifying NICM patients at risk of SCD.