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Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs). This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM). Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia). The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MF VA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MF VA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01). MF VA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MF VA. In contrast, LVEF was a poor discriminator of arrhythmic risk. [ABSTRACT FROM AUTHOR]

Objectives: To identify possible etiology-specific differences in preoperative risk factors for major adverse events during Impella 5.5 support in patients with ischemic (ICM) and nonischemic cardiomyopathy (NICM). Methods: From October 2019 to January 2023, 228 Impella 5.5 devices were inserted at our institution. Patients were stratified into ICM (n = 124) and NICM (n = 104) cohorts. The primary outcome was a composite of death/stroke/new-onset dialysis while actively receiving Impella 5.5 support. Random forests identified preoperative factors predictive of the primary outcome separately for each cohort, with ranking by variable importance. Results: The primary outcome occurred in 42 (34%) patients with ICM and 35 (34%) patients with NICM. Twenty-one (17%) patients with ICM and 21 (20%) patients with NICM died on Impella 5.5; stroke occurred in 12 (9.7%) patients with ICM and 3 (2.9%) patients with NICM, and new-onset dialysis was initiated in 23 (19%) patients with ICM and 24 (23%) patients with NICM while actively receiving Impella 5.5 support. Risk factors reflecting systemic and myocardial cellular injury, end-organ and cardiopulmonary failure, right ventricular dysfunction, and smaller left ventricular dimensions were most predictive of adverse outcomes in both cohorts. Indications for Impella 5.5 and device strategy (bridge to recovery, advanced therapies, or decision) were not top risk factors in either cohort. Conclusions: Risk factors related to preoperative stability, right ventricular dysfunction, and left ventricular size were more predictive of adverse outcomes while actively receiving Impella 5.5 support than indication or device strategy. These factors could help identify high-risk patients who may benefit from additional tailored management to reduce their risk for these impactful adverse outcomes while on Impella 5.5 support.

Abstract Background Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. Methods We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. Results MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670–0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199–1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. Conclusion Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.

Background: Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. Methods: We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. Results: MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670–0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199–1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. Conclusion: Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication. [ABSTRACT FROM AUTHOR]

Introduction: Scar substrate in nonischemic cardiomyopathy (NICM) patients is often difficult to identify. Advances in cardiac imaging, especially using late iodine‐enhanced computed tomography (LIE‐CT), allow better characterization of scars giving rise to ventricular tachycardia (VT). Currently, there are limited data on clinical correlates of CT‐derived scar substrates in NICM. We sought assess the relationship between scar location on LIE‐CT and outcomes after radiofrequency catheter ablation (RFCA) in NICM patients with VT. Methods: From 2020 to 2022, consecutive patients with NICM undergoing VT RFCA with integration of cardiac CT scar modeling (inHeart, Pessac, France) were included at two US tertiary care centers. The CT protocol included both arterial‐enhanced imaging for anatomical modeling and LIE‐CT for scar assessment. The distribution of substrate on CT was analyzed in relation to patient outcomes, with primary endpoints being VT recurrence and the need for repeat ablation procedure. Results: Sixty patients were included (age 64 ± 12 years, 90% men). Over a median follow‐up of 120 days (interquartile range [IQR]: 41–365), repeat ablation procedures were required in 32 (53%). VT recurrence occurred in 46 (77%), with a median time to recurrence of 40 days (IQR: 8–65). CT‐derived total scar volume positively correlated with intrinsic QRS duration (r =.34, p = 0.008). Septal scar was found on CT in 34 (57%), and lateral scar in 40 (7%). On univariate logistic regression, septal scar was associated with increased odds of repeat ablation (odds ratio [OR]: 2.9 [1.0–8.4]; p = 0.046), while lateral scar was not (OR: 0.9 [0.3–2.7]; p = 0.855). Septal scar better predicted VT recurrence when compared to lateral scar, but neither were statistically significant (septal scar OR: 3.0 [0.9–10.7]; p = 0.078; lateral scar OR: 1.7 [0.5–5.9]; p = 0.391). Conclusion: In this tertiary care referral population, patients with NICM undergoing VT catheter ablation with septal LIE‐CT have nearly threefold increased risk of need for repeat ablation. [ABSTRACT FROM AUTHOR]

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Abstract Background In some patients with nonischemic cardiomyopathy (NICM), left ventricular (LV) function improves with medical assistance, resulting in left ventricular reverse remodeling (LVRR). However, predictors of LVRR are not fully understood. The left atrium (LA) has been reported as a prognostic predictor in patients with heart failure (HF). The present study aimed to evaluate clinical predictors of LVRR related to LA function on cardiac magnetic resonance (CMR). Methods A total of 103 patients with reduced left ventricular ejection fraction (LVEF) were enrolled in this retrospective study between September 2015 and July 2021. CMR parameters, including strain data, were measured in all patients. Echocardiographic data obtained approximately 2 years after enrollment were analyzed to assess LVRR. Results LVRR occurred in 46 patients (44.7%) during follow-up. The value of LA conduit strain was higher in the LVRR group than in the non-LVRR group (6.6 [interquartile range (IQR): 5.6–9.3]% versus 5.0 [IQR: 3.0-6.2]%; p 6.2% compared to those with ⩽6.2%. (log-rank test, p = 0.019). Conclusions LA conduit strain derived from CMR is an independent predictor of LVRR in patients with NICM.

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all‐cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta‐analysis study. Methods: We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case–control, or analytical cross‐sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all‐cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta‐Analysis" software, Version 2.0. Results: Nineteen cohort and three analytical cross‐sectional studies were included in this meta‐analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all‐cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388–2.656, p < 0.0001/pooled HR: 1.729; 95% CI: 1.327–2.251, p < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644–2.533, p < 0.0001/pooled HR: 3.626; 95% CI: 2.119–6.204, p < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07–5.71, p < 0.0001/pooled HR: 3.21; 95% CI: 2.04–5.06, p < 0.0001). Conclusion: Fragmented QRS could be a prognostic marker for all‐cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM. [ABSTRACT FROM AUTHOR]

Background or Purpose: The prognosis of m ixed cardiomyopathy (CMP) in patients with implanted cardioverter-defibrillators (ICDs) has not been investigated. We aim to study the demographic, clinical, device therapies and survival characteristics of mixed CMP in a cohort of patients implanted with a defibrillator. Methods: The term mixed CMP was used to categorise patients with impaired left ventricular ejection fraction attributed to documented non-ischemic triggers with concomitant moderate coronary artery disease. This is a single center observational cohort of 526 patients with a mean follow-up of 8.7 ± 3.5 years. Results: There were 42.5% patients with ischemic cardiomyopathy (ICM), 26.9% with non-ischemic cardiomyopathy (NICM) and 30.6% with mixed CMP. Mixed CMP, compared to NICM, was associated with higher mean age (69.1 ± 9.6 years), atrial fibrillation (55.3%) and greater incidence of comorbidities. The proportion of patients with mixed CMP receiving device shocks was 23.6%, compared to 18.4% in NICM and 27% in ICM. The VT cycle length recorded in mixed CMP (281.6 ± 43.1 ms) was comparable with ICM (282.5 ± 44 ms; p = 0.9) and lesser than NICM (297.7 ± 48.7 ms; p = 0.1). All-cause mortality in mixed CMP (21.1%) was similar to ICM (20.1%; p = 0.8) and higher than NICM (15.6%; p = 0.2). The Kaplan–Meier curves revealed hazards of 1.57 (95% CI: 0.91, 2.68) for mixed CMP compared to NICM. Conclusion: In a cohort of patients with ICD, the group with mixed CMP represents a phenotype predominantly comprised of the elderly with a higher incidence of comorbidities. Mixed CMP resembles ICM in terms of number of device shocks and VT cycle length. Trends of long-term prognosis of patients with mixed CMP are worse than NICM and similar to ICM. [ABSTRACT FROM AUTHOR]

IntroductionSignal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM.Methods and resultsThis retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence.ConclusionIn our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

Abstract Background and Aims Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all‐cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta‐analysis study. Methods We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case–control, or analytical cross‐sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all‐cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using “Comprehensive Meta‐Analysis” software, Version 2.0. Results Nineteen cohort and three analytical cross‐sectional studies were included in this meta‐analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all‐cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388–2.656, p

Among patients with ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM), myocardial fibrosis is associated with an increased risk for ventricular arrhythmia (VA). Growing evidence suggests that myocardial fat contributes to ventricular arrhythmogenesis. However, little is known about the volume and distribution of epicardial adipose tissue and intramyocardial fat and their relationship with VAs. The purpose of this study was to assess the association of contrast-enhanced computed tomography (CE-CT)–derived left ventricular (LV) tissue heterogeneity, epicardial adipose tissue volume, and intramyocardial fat volume with the risk of VA in ICM and NICM patients. Patients enrolled in the PROSE-ICD registry who underwent CE-CT were included. Intramyocardial fat volume (voxels between –180 and –5 Hounsfield units [HU]), epicardial adipose tissue volume (between –200 and –50 HU), and LV tissue heterogeneity were calculated. The primary endpoint was appropriate ICD shocks or sudden arrhythmic death. Among 98 patients (47 ICM, 51 NICM), LV tissue heterogeneity was associated with VA (odds ratio [OR] 1.10; P =.01), particularly in the ICM cohort. In the NICM subgroup, epicardial adipose tissue and intramyocardial fat volume were associated with VA (OR 1.11, P =.01; and OR = 1.21, P =.01, respectively) but not in the ICM patients (OR 0.92, P =.22; and OR = 0.96, P =.19, respectively). In ICM patients, increased fat distribution heterogeneity is associated with VA. In NICM patients, an increased volume of intramyocardial fat and epicardial adipose tissue is associated with a higher risk for VA. Our findings suggest that fat's contribution to VAs depends on the underlying substrate. [ABSTRACT FROM AUTHOR]

• Out of 2319 patients with HFrEF (LVEF ≤35%) secondary to NICM, 465 (20%) experienced complete myocardial recovery (LVEF ≥50%). • From those patients who recovered, 80% experienced recurrent LV dysfunction within 7 years. • Compared with patients with HFrEF, patients with HFrecEF tended to have better clinical outcomes. • Among patients who experienced recovery, a longer duration of recovery was associated with both longer overall survival and longer survival after recurrence of LV dysfunction. Duration of recovery and long-term outcomes have not been well-described in a large cohort of patients with heart failure with recovered ejection fraction (HFrecEF) owing to nonischemic cardiomyopathy. The aim of the study was to characterize the duration of recovery and long-term outcomes of patients with HFrecEF. We performed a retrospective analysis of our institution's databases. Only patients with nonischemic cardiomyopathy, a chronic HF diagnosis, and a previous left ventricular ejection fraction (LVEF) of ≤35% who had a subsequent LVEF of ≥50% were considered to have recovery. Patients with an LVEF of ≤35% who did not recover served as the comparison group. Included were 2319 patients with an LVEF of ≤35%, of whom 465 (20% [18.4%-21.7%]) met the above criteria for recovery (HFrecEF group). Recovery in the HFrecEF group was temporary in most cases, with 50% of patients experiencing a decline in LVEF to <50% within 3.5 [interquartile range 2.4-4.9] years after the day of recovery. Age and sex adjusted death and hospitalization were lower in the HFrecEF group than the HFrEF group (HR 0.29 [interquartile range 0.20–0.41] for death and 0.44 [interquartile range 0.32–0.60] for HF hospitalization, P <.0001 for both). Longer recovery was associated with better survival, with patients spending >5 years in recovery (LVEF of ≥50%) displaying the highest survival rates (83% alive at 10 years after recovery). Survival after recurrence of LV dysfunction was longer for those whose recovery duration was >1 year. Patients with nonischemic HFrecEF display a unique clinical course. Although recovery is temporary in most cases, patients with HFrecEF display lower mortality and hospitalization rates, with the more durable the recovery of LV systolic function, the longer survival can be anticipated. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Variants of cardiomyopathy genes in patients with nonischemic cardiomyopathy (NICM) generate various phenotypes of cardiac scar and delayed enhancement cardiac magnetic resonance (DE‐CMR) imaging which may impact ventricular tachycardia (VT) management. Methods: The objective was to compare the findings of cardiomyopathy genetic testing on DE‐CMR imaging and long‐term outcomes among patients with NICM undergoing VT ablation procedures. Image phenotyping and genotyping were performed in a consecutive series of patients referred for VT ablation and correlated to survival free of VT. Scar depth index (SDI) (% of scar at 0‐3 mm, 3‐5 mm and >5 mm projected on the closest endocardial surface) was determined. Results: Forty‐three patients were included (11 women, 55 ± 14 years, ejection fraction (EF) 45 ± 16%) and were followed for 3.4 ± 2.9 years. Pathogenic variants (PV) were identified in 16 patients (37%) in the following genes: LMNA (n = 5), TTN (n = 5), DSP (n = 2), AMLS1 (n = 1), MYBPC3 (n = 1), PLN (n = 1), and SCN5A (n = 1). A ring‐like septal scar (RLSS) pattern was more often seen in patients with pathogenic variants (66% vs 15%, p =.001). RLSS was associated with deeper seated scars (SDI >5 mm 30.6 ± 22.6% vs 12.4 ± 16.2%, p =.005), and increased VT recurrence (HR 5.7 95% CI[1.8‐18.4], p =.003). After adjustment for age, sex, EF, and total scar burden, the presence of a PV remained independently associated with worse outcomes (HR 4.7 95% CI[1.22‐18.0], p =.02). Conclusions: Preprocedural genotyping and scar phenotyping is beneficial to identify patients with a favorable procedural outcome. Some PVs are associated with an intramural, deeper seated scar phenotype and have an increase of VT recurrence after ablation. [ABSTRACT FROM AUTHOR]

Nonischemic cardiomyopathy (NICM) is common and patients are at significant risk for early mortality secondary to ventricular arrhythmias. Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy to decrease sudden cardiac death (SCD) in patients with heart failure and reduced left ventricular ejection fraction. However, in randomized clinical trials comprised solely of patients with NICM, primary prevention ICDs did not confer significant mortality benefit. Moreover, left ventricular ejection fraction has limited sensitivity and specificity for predicting SCD. Therefore, precise risk stratification algorithms are needed to define those at the highest risk of SCD. This review examines mechanisms of sudden arrhythmic death in patients with NICM, discusses the role of ICD therapy and treatment of heart failure for prevention of SCD in patients with NICM, examines the role of cardiac magnetic resonance imaging and computational modeling for SCD risk stratification, and proposes new strategies to guide future clinical trials on SCD risk assessment in patients with NICM. [Display omitted] • NICM patients are at increased risk for SCD; however, current guidelines are insufficient in identifying those who may benefit from ICD therapy. • Identifying the underlying cause for the NICM is important in understanding the disease trajectory. CMR imaging adds additional information in understanding the risk for SCD. • Optimizing guideline-directed medical therapy for heart failure, incorporating clinical parameters, and detailed myocardial structural assessment will be critical to personalized decision-making in SCD risk stratification. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies have questioned the role of implanted cardiac defibrillators (ICDs) in nonischemic cardiomyopathy (NICM). Cardiac resynchronization therapy (CRT) can be delivered by a pacemaker (CRT-P) or an ICD (CRT-D). This meta-analysis assessed the effect of CRT-P versus CRT-D on mortality in patients with NICM. Methods Databases were searched for studies reporting the effect of CRT on all-cause mortality in patients with nonischemic cardiomyopathy (Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL). The primary endpoint was all-cause mortality. The minimum duration of follow-up required for inclusion was one year. The search was not restricted to time or publication status. Results The literature search identified 955 candidate studies, 15 studies and 22,763 patients were included. Mean follow-up was 53 months (17–100 months). CRT-D in NICM was associated with lower all-cause mortality (log HR − 0.169, SE 0.055; p = 0.002) compared to CRT-P. Heterogeneity: df = 15 (P 0.03), I2 = 43; test for overall effect: Z = − 3.043 (P = 0.002). Conclusion CRT-D in NICM was associated with lower all-cause mortality than CRT-P.

BackgroundCardiac resynchronization therapy (CRT) is a major device therapy used to treat patients suffering from heart failure (HF) and electrical asynchrony. It can improve HF symptoms, reduce HF hospitalization time, and improve long-term survival in HF with and without implantable cardioverter (ICD) therapy. However, the benefit of defibrillator therapy in CRT-eligible patients with nonischemic cardiomyopathy (NICM) remains unknown. As a result, we conducted a systematic review and meta-analysis to compare clinical outcomes in patients with NICM and HF who were treated with implantable CRT defibrillators (CRT-D) vs. a CRT pacemaker (CRT-P) alone.MethodsWe searched the electronic databases PubMed, Embase, and Cochrane for all studies comparing CRT-D vs. CRT-P treatment in patients with NICM. The time frame was from 1990 to September 2022. All-cause mortality and cardiovascular mortality were the primary clinical outcomes of interest to us. To pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), a random-effects model with inverse variance was used.ResultsA pooled meta-analysis included two randomized controlled trials (RCTs), each with 1,200 CRT-eligible patients with NICM (592 with CRT-D and 608 with CRT-P) and nine cohort studies representing 27,568 CRT-eligible patients with NICM (16,196 with CRT-D and 11,372 with CRT-P). The adjusted HR for all-cause mortality for CRT-D vs. CRT-P was 0.90 (95% CI, 0.81-0.99). In a subgroup analysis of two RCTs and nine cohort studies, the adjusted HR for all-cause mortality was 0.72 (95% CI, 0.43–1.19) and HR 0.92 (95% CI, 0.83–1.03) for CRT-D vs. CRT-P, respectively.ConclusionWith the addition of defibrillation leads, we found a significantly lower risk of all-cause mortality in patients with NICM, but this association was not found in subgroup analyses of RCTs and observational studies.

Iron overload cardiomyopathy has been described in patients who develop acute heart failure after liver transplantation but few reports of this are available. We present a case of a patient with end-stage liver disease who underwent a deceased donor liver transplantation and developed acute onset systolic heart failure with reduced left ventricular ejection fraction. A cardiac magnetic resonance image demonstrated late gadolinium enhancement with diffuse enhancement globally and T1 mapping with severely decreased pre-contrast T1 values suggesting iron overload cardiomyopathy. The patient was treated with iron chelating therapy as well as heart failure guideline-directed medical therapy with subsequent improvement in cardiac function on follow-up magnetic resonance images. Despite our patient's diagnosis of iron overload cardiomyopathy, her iron studies showed normal serum iron and ferritin levels and no evidence of hepatic iron deposition in the transplanted liver. [ABSTRACT FROM AUTHOR]

Introduction: Substrate‐based ablation for ventricular tachycardia (VT) using Ripple map (RM) is an effective treatment strategy for patients with ischemic cardiomyopathy but has yet to be evaluated in patients with nonischemic cardiomyopathy (NICMO). The aim of this study is to determine the feasibility and effectiveness of an RM‐based ablation for NICMO patients. Methods and Results: This was a single‐center, retrospective study including all NICMO patients undergoing VT ablation at St Vincent Hospital between January 1, 2018 and January 12, 2019. Retrospective RM analysis was performed on those that had a substrate‐based ablation to identify the location and number of Ripple channels as well as their proximity to ablation lesions. Thirty‐three patients met the inclusion criteria and had a median age of 65 (58, 73.5) with 15.2% of the population being female, and were followed for a median duration of 451 (217.5, 586.5) days. Of these patients, 23 (69.7%) had a substrate‐based ablation with a median procedural duration of 196.4 (186.8, 339) min, 1946 (517, 2750) points collected per map, and 277 (141, 554) points were within the scar. Two (8.6%) procedural complications occurred, and 7 (30.4%) patients had VT recurrence during follow‐up. RM analysis revealed an average of two Ripple channels and the patients without VT recurrence had ablation performed closer to the Ripple channels: 0 (0, 4.7) versus 14.3 (0, 23.5) cm; p =.02. Conclusion: An RM‐based substrate ablation can be performed in NICMO patients and ablation within Ripple channels is a predictor of VT freedom. [ABSTRACT FROM AUTHOR]

Purpose: With extravascular implantable cardioverter defibrillator leads placed beneath the sternum, it is important to quantify heart motion relative to the rib cage with postural changes and respiration. Methods: MRI scans from five males and five females were collected in upright and supine postures at end inspiration [n = 10 each]. Left and right decubitus [n = 8 each] and prone [n = 5] MRIs at end inspiration and supine MRIs at end expiration [n = 5] were collected on a subset. Four cardiothoracic measurements, six cardiac measurements, and six cardiac landmarks were collected to measure changes across different postures and stages of respiration. Results: The relative location of the LV apex to the nearest intercostal space was significantly different between the supine and decubitus postures (average ± SD difference: − 15.7 ± 11.4 mm; p < 0.05). The heart centroid to xipho-sternal junction distance was 9.7 ± 7.9 mm greater in the supine posture when compared to the upright posture (p < 0.05). Cardiac landmark motion in the lateral direction was largest due to postural movement (range 23–50 mm) from the left decubitus to the right decubitus posture, and less influenced by respiration (5–17 mm). Caudal-cranial displacement was generally larger due to upright posture (13–23 mm caudal) and inspiration (7–20 mm cranial). Conclusions: This study demonstrates that the location of the heart with respect to the rib cage varies with posture and respiration. The gravitational effects of postural shifts on the heart position are roughly 2–3 times larger than the effects of normal respiration. [ABSTRACT FROM AUTHOR]

1,1-Difluoroethane (DFE) cardiomyopathy results from the direct inhalation of toxic halogenated hydrocarbons. We present a case series of acute DFE cardiomyopathy illustrating the typical presentation of severe DFE cardiomyopathy along with a detailed description of its mechanism of injury. (Level of Difficulty: Advanced.)

Techniques for catheter ablation have evolved to effectively treat a range of ventricular arrhythmias. Pre-operative electrocardiographic and cardiac imaging data are very useful in understanding the arrhythmogenic substrate and can guide mapping and ablation. In this review, we focus on best practices for catheter ablation, with emphasis on tailoring ablation strategies, based on the presence or absence of structural heart disease, underlying clinical status, and hemodynamic stability of the ventricular arrhythmia. We discuss steps to make ablation safe and prevent complications, and techniques to improve the efficacy of ablation, including optimal use of electroanatomical mapping algorithms, energy delivery, intracardiac echocardiography, and selective use of mechanical circulatory support. [ABSTRACT FROM AUTHOR]

The implantable cardiac defibrillator (ICD) is common for the management of nonischemic cardiomyopathy (NICM). Mortality is a crucial issue for patients with NICM. We can understand the mortality events of ICD versus medicine treatment via a systemic review and meta‐analysis of randomized clinical trials. The comparison between ICD treatment and medicine treatment was performed to find if the ICD treatment can be associated with lower relative risk and hazard ratio of mortality than the medicine treatment. In addition, the different kinds of mortality events were analyzed for the ICD treatment. After a restricted selection, 9 studies with a total of 4001 NICM patients were enrolled. The focused outcome was the events of all‐cause mortality, sudden cardiac death, and cardiovascular death. The results showed that ICD treatment might be associated with lower relative risk and hazard ratio of all‐cause mortality and sudden cardiac death. However, the relative risk and hazard ratio of cardiovascular mortality was not significantly different between ICD treatment and medicine treatment. In the current meta‐analysis, the ICD treatment might show a lower relative risk and hazard ratio of all‐cause mortality and sudden cardiac death when compared with medicine treatment. However, no significant differences were observed in cardiovascular mortality between ICD and medicine treatment. [ABSTRACT FROM AUTHOR]

The treatment of ventricular tachycardia caused by nonischemic cardiomyopathy (NICM-VT) is challenging in clinical practice, however, the related clinical data of catheter ablation for NICM-VT are limited. This paper reviews the progress of catheter ablation for NICM-VT from three aspects: clinical efficacy, mapping strategy, and future prospect. [ABSTRACT FROM AUTHOR]

Background: Late gadolinium enhanced cardiac magnetic resonance (LGE-CMR) imaging may help identify radiofrequency ablation lesions, which have been poorly described in patients with nonischemic cardiomyopathy (NICM).Objectives: The purpose of this study was to describe LGE-CMR characteristics of ablation lesions in patients with NICM and correlate them with histopathology.Methods: Twenty-six patients (24 men; ejection fraction 38% ± 14%; age 61 ± 9 years) who had undergone CMR imaging after ventricular tachycardia (VT) ablation were included. Areas of both dark and bright core lesions correlating with previous radiofrequency ablation lesions were identified. Histology was performed on an explanted heart.Results: Mean time between the ablation procedure and the LGE-CMR study was 8 [2-20] months. Twenty-three of 26 patients demonstrated dark core lesions (volume 2.16 ± 1.8 cm3; thickness 3.6 ± 1.3 mm) with transmurality of 42% ± 16% overlaying areas of intramural or transmural LGE. Fourteen of 26 patients demonstrated bright core lesions (volume 0.8 ± 0.6 cm3; depth 4.15 ± 1.76 mm) with transmurality of 34% ± 14%, which was located in areas without underlying LGE in 11 of 13 patients. Both dark and bright core lesions were visualized on standard clinical LGE-CMR imaging obtained in the acute setting and chronic settings (within 3 days and up to 2090 days postablation). Histopathologic analysis demonstrated coagulation necrosis in the area that corresponded to dark core lesions in the postablation CMR.Conclusion: Ablation lesions can be detected by LGE-CMR after VT ablation in NICM patients and have a different appearance than scar tissue. These lesions can be observed in the acute and chronic settings after ablations. [ABSTRACT FROM AUTHOR]

Background: The ability to predict recovery of left ventricular ejection fraction (LVEF) in response to guideline-directed therapy among patients with nonischemic cardiomyopathy is desired. We sought to determine whether left ventricular endocardial unipolar voltage measured during invasive electroanatomic mapping could be used to predict LVEF recovery among those with recent-onset nonischemic cardiomyopathy., Methods: We analyzed the left ventricular voltage maps of patients included in the eMAP trial (Electrogram-Guided Myocardial Advanced Phenotyping; NCT03293381), a prospective, nonrandomized, interventional trial conducted at 2 institutions between 2017 and 2020. Patients had recent-onset nonischemic cardiomyopathy defined by LVEF ≤45% and development of symptoms or signs of heart failure within the past 6 months. Detailed voltage maps of the left ventricular endocardium were generated using the CARTO electroanatomic mapping system. Abnormal unipolar amplitude was defined as <8.27 mV. The primary end point was recovery of LVEF (Recovery) defined by a 1-year LVEF ≥50% or ≥45% with ≥10% increase from baseline., Results: Of the 29 enrolled patients (median age, 49 years [25th percentile, 39; 75th percentile, 59], 8 females [27.6%]), LVEF recovered in 13 (44.8%) by 1-year follow-up. The percentage of total endocardial surface area with unipolar voltage abnormality (AUA) was significantly lower among Recovery patients than No Recovery patients (18.2% [6.4, 22.4] versus 80.0% [29.5, 90.9]; P =0.004). Percent AUA was associated with lower likelihood of Recovery (odds ratio, 0.64 per 10% increase in AUA; 95% CI, 0.47-0.88; P =0.006). A 28% cutoff value for percent AUA was 92% sensitive and 75% specific with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.63-0.99; P =0.001) for predicting recovery versus no recovery. The majority of patients (12 of 13; 92.3%) with a percent AUA >28% did not recover., Conclusions: Left ventricular unipolar voltage abnormality is a potent predictor of LVEF recovery among patients recently diagnosed with nonischemic cardiomyopathy. Detailed left ventricular unipolar voltage mapping could therefore be used as a valuable prognostic tool in guiding treatment decisions.

Introduction: The implantable cardioverter defibrillator reduces mortality among patients with heart failure (HF) due to ischemic heart disease. Clinical trial data have called into question the benefit of an ICD in patients with HF due to nonischemic cardiomyopathy (NICM). We developed a risk stratification score for ventricular tachyarrhythmia (VTA) among patients with NICM receiving a primary prevention ICD., Methods: The study population comprised 1515 patients with NICM who were enrolled in the landmark MADIT trials. Fine and Gray analysis was used to develop a model to predict the occurrence of VTAs and ICD therapies while accounting for the competing risk of non-arrhythmic mortality. External validation was carried out in the RAID Trial population., Results: Four risk factors associated with increased risk for VTA were identified: male sex, left ventricular ejection fraction ≤25%, no indication for cardiac resynchronization therapy with a defibrillator (CRT-D), and Black race. A score was generated based on this model, and patients were stratified into low (N = 390), intermediate (N = 728), and high-risk (N = 387) groups. The 5-year cumulative incidences of VTA were 15%, 24%, and 42%, respectively. Application of score groups for the secondary endpoints of Fast VT or VF and Appropriate ICD Shock revealed similar findings. Recurrent event analysis yielded consistent results. The AUC in the validation cohort for the endpoint of Appropriate ICD Shock was 69.3., Conclusions: Our study shows that patients with NICM can be risk stratified using demographic and clinical variables and may be used when evaluating such patients for a primary prevention ICD., (© 2024 Wiley Periodicals LLC.)

Background: Ventricular tachycardia (VT) substrate in patients with nonischemic cardiomyopathy (NICM) is complex in distribution and intramural location., Objectives: This study sought to test the hypothesis that myocardial lipomatous metaplasia (LM) is a vital anatomic substrate for VT corridors in patients with NICM and VT, and that LM stabilizes current propagation in VT corridors., Methods: Among 49 patients with NICM in the 2-center INFINITY (Prospective Intra-Myocardial Fat Deposition and Ventricular Tachycardia in Cardiomyopathy) Study, potential VT viable corridors within the myocardial scar and/or LM were computed from late gadolinium enhancement cardiac magnetic resonance images and were registered with electroanatomical maps. Corridors passing through VT entrance, isthmus, and/or exit sites, estimated by entrainment or pace mapping, were defined as VT corridors. LM was separately distinguished from scar using computed tomography. The SD of current amplitude along each corridor was measured., Results: Compared with 151 non-VT corridors, 35 VT corridors traversed a substantially higher volume of LM, with a median 236.6 mg (IQR: 13.5-903.4 mg) vs 5.8 mg (IQR: 0.0-57.9 mg) (P < 0.001). Among corridors with computable current amplitude, 28 VT corridors exhibited substantially lower current variation along the corridors, with SD 8.0 μA (25th-75th percentile: 6.1-10.3 μA) vs 14.9 μA (25th-75th percentile: 8.5-23.7 μA) among 71 non-VT corridors (P < 0.001). Individual VT circuit sites (95 out 118) were highly colocalized with LM., Conclusions: VT circuitry corridors in NICM are more likely to traverse LM and exhibit reduced current amplitude variation compared with bystander corridors., Competing Interests: Funding Support and Author Disclosures The INFINITY (Prospective Intra-Myocardial Fat Deposition and Ventricular Tachycardia in Cardiomyopathy) study is funded by the National Institute of Health grant 1R01HL142893-01. Dr Xu is funded by American Heart Association Postdoctoral fellowship (23POST909139). Dr Witschey is supported by NIH R01 HL169378, R01 HL137984 and P41 EB029460. The study was also supported by software and funds from ADAS Software. Dr Nazarian is a consultant for Biosense Webster and Dyne Pharmaceuticals; and principal investigator for research funding from Biosense Webster, ADAS Software, and the US NIH. Dr Marchlinski has served as a consultant for Abbott Medical, Biosense Webster, Biotronik, and Medtronic Inc. Drs Callans and Chrispin have served as consultants for Abbott Medical, Biosense Webster and Boston Scientific. The University of Pennsylvania Conflict of Interest Committee manages all commercial arrangements. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Life-threatening dysrhythmias remain a significant cause of mortality in patients with nonischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillators (ICD) effectively reduce mortality in patients who have survived a life-threatening arrhythmic event. The evidence for survival benefit of primary prevention ICD for patients with high-risk NICM on guideline-directed medical therapy is not as robust, with efficacy questioned by recent studies. In this review, we summarize the data on the risk of life-threatening arrhythmias in NICM, the recommendations, and the evidence supporting the efficacy of primary prevention ICD, and highlight tools that may improve the identification of patients who could benefit from primary prevention ICD implantation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Endocardial electrogram (EGM) characteristics in nonischemic cardiomyopathy (NICM) have not been explored adequately for prognostication., Objective: We aimed to study correlation of bipolar and unipolar EGM characteristics with left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT) in NICM., Methods: Electroanatomic mapping of the left ventricle was performed. EGM characteristics were correlated with LVEF. Differences between groups with and without VT and predictors of VT were studied., Results: In 43 patients, unipolar EGM variables had better correlation with baseline LVEF than bipolar EGM variables: unipolar voltage (r = +0.36), peak negative unipolar voltage (r = -0.42), peak positive unipolar voltage (r = +0.38), and percentage area of unipolar low-voltage zone (LVZ; r = -0.41). Global mean unipolar voltage (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2-0.8), extent of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3), and percentage area of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3) were significant predictors of VT. For classification of patients with VT, extent of unipolar LVZ had an area under the curve of 0.82 (95% CI, 0.69-0.95; P < .001), and percentage area of unipolar LVZ had an area under the curve of 0.83 (95% CI, 0.71-0.96; P = .01). Cutoff of >3 segments for extent of unipolar LVZ had the best diagnostic accuracy (sensitivity, 90%; specificity, 67%) and cutoff of 33% for percentage area of unipolar LVZ had the best diagnostic accuracy (sensitivity, 95%; specificity, 60%) for VT., Conclusion: In NICM, extent and percentage area of unipolar LVZs are significant predictors of VT. Cutoffs of >3 segments of unipolar LVZ and >33% area of unipolar LVZ have good diagnostic accuracies for association with VT., Competing Interests: Disclosures Dr Sanders reports having served on the advisory boards of Medtronic, Abbott Medical, Boston Scientific, CathRx, and PaceMate and that the University of Adelaide has received on his behalf research funding and/or lecture and/or consulting fees from Medtronic, Abbott Medical, and Boston Scientific. Dr Pathak reports having served on the advisory boards of Medtronic, Abbott Medical, and Boston Scientific and that Canberra Heart Rhythm Foundation has received on his behalf research funding and/or lecture and/or consulting fees from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Abstract Cell therapy involves transplantation of human cells to promote repair of diseased or injured tissues and/or cells. Only a limited number of mostly small‐scale trials have studied cell therapy in nonischemic cardiomyopathy (NICM). We performed a meta‐analysis of randomized clinical trials (RCTs) to assess the safety and efficacy of cell therapy in NICM. Electronic databases were searched for relevant RCTs from inception until August 2020. Outcomes assessed were left ventricular ejection fraction (LVEF), left ventricular end‐diastolic diameter or volume (LVEDD), quality of life (QoL) indices, and major adverse cardiac events (MACEs). Weighted mean differences (MDs) and standardized mean differences (SMDs) were calculated using random‐effects methods. Eleven RCTs with 574 participants were included in the analysis. There was a significant increase in mean LVEF (MD, 4.17%; 95% confidence interval [CI] = 1.66‐6.69) and modest decrease in LVEDD (SMD, −0.50; 95% CI = −0.95 to −0.06) in patients treated with cell therapy compared with controls. Cell therapy was also associated with improvement in functional capacity, as assessed by the 6‐minute walking distance (MD, 72.49 m; 95% CI = 3.44‐141.53). No significant differences were seen in MACEs and QoL indices between treated and control groups. This meta‐analysis suggests that cell therapy may improve LV systolic function and may be associated with improvement in LVEDD and functional capacity compared with maximal medical therapy. Cell therapy was safe, with no significant difference in MACEs between treatment and control groups. However, given the limitations of current studies, larger well‐designed RCTs are needed to evaluate the efficacy of cell therapy in patients with NICM.

Background: Recurrent ventricular tachycardia (VT) due to dilated cardiomyopathy (DCM) is difficult to treat, and long-term outcome data are limited.Objectives: The aim of this study was to identify predictors of mortality or heart transplantation (HTx) and VT recurrence.Methods: Consecutive patients with DCM accepted for radiofrequency catheter ablation (RFCA) of VT at 9 centers were prospectively enrolled and followed.Results: Of 281 consecutive patients (mean age 60 ± 13 years, 85% men, mean left ventricular ejection fraction [LVEF] 36% ± 12%), 35% had VT storm, 20% had incessant VT, and amiodarone was unsuccessful in 68%. During follow-up of 21 months (IQR: 6-30 months), 67 patients (24%) died or underwent HTx, and 138 (49%) had VT recurrence (45 within 30 days, defined as early); the 4-year rate of VT recurrence or mortality or HTx was 70%. Independent predictors of mortality or HTx were early VT recurrence (HR: 2.92; 95% CI: 1.37-6.21; P < 0.01), amiodarone at discharge (HR: 3.23; 95% CI: 1.43-7.33; P < 0.01), renal dysfunction (HR: 1.92; 95% CI: 1.01-3.64; P = 0.046), and LVEF (HR: 1.36; 95% CI: 1.0-1.84; P = 0.052). LVEF ≤32% identified patients at risk for mortality or HTx (area under the curve: 0.75). Mortality or HTx per 100 person-years was 40.4 events after early, compared with 14.2 events after later VT recurrence and 8.5 events with no VT recurrence after RFCA (P < 0.01 for both). Patients with early recurrence and LVEFs ≤32% had a 1-year rate of mortality or HTx of 55%. VT recurrence was predicted by prior implantable cardioverter-defibrillator shocks, basal anteroseptal VT origin, and procedural failure but not LVEF.Conclusions: Patients with DCM needing RFCA for VT are a high-risk group. Following RFCA, approximately one-half remain free of VT recurrence. Early VT recurrence with LVEF ≤32% identifies those at very high risk for mortality or HTx, and screening for mechanical support or HTx should be considered. Late VT recurrence after RFCA does not predict worse outcome. [ABSTRACT FROM AUTHOR]

Background: Although the mean age of sudden cardiac death (SCD) victims has increased during recent decades, overall incidence has remained relatively stable. Small but very important proportion of SCDs occur in subjects under 40 years of age and temporal trends in the incidence and characteristics of SCD in this age-group are not well known. Methods: The Fingesture study has prospectively gathered data from 5,869 consecutive autopsy verified SCD victims in Northern Finland during 1998–2017. On the basis of Finnish law, all who die unexpectedly undergo autopsy. Results: Out of total 5,869 SCDs, 160 occurred in subjects under 40 years of age (3%) indicating a total incidence of 2.9/100,000/year. Incidence decreased during the study period: 4.0/100,000/year (n = 50) in 1998–2002, 3.7/100,000/year (n = 45) in 2003–2007, 2.5/100,000/year (n = 36) in 2008–2012, and 1.5/100,000/year (n = 29) in 2013–2017. Coronary artery disease (CAD) was the cause of death in 46 SCD victims (29%). Among nonischemic causes, most common were obesity-related hypertrophic myocardial disease (24%), primary myocardial fibrosis (19%), and hypertensive myocardial disease (6%). The incidence of SCD caused by CAD decreased as follows: 1.5/100,000/year in 1998–2002, 1.2/100,000/year in 2003–2007, 0.6/100,000/year in 2008–2012, and 0.2/100,000/year in 2013–2017. Proportion of male gender (81%) and obesity as a comorbidity (body mass index >30 kg/m2, 40%) remained relatively stable during the period (p = 0.58 and p = 0.79, respectively). Conclusions: The incidence of SCD in subjects under 40 years of age has decreased in Northern Finland during 1998–2017. According to autopsy data, most of the deaths are due to nonischemic myocardial diseases and relative proportion of CAD has decreased. [ABSTRACT FROM AUTHOR]

Background: Moderate to severe aortic valve insufficiency (AI) in patients undergoing left ventricular assist device (LVAD) implantation is a significant complication which occurs in up to 10.7% of patients in the INTERMACS database and has profound consequences for survival. Preoperative Impella use is associaed with greater post‐LVAD AI. Case Presentation: 56 y/o Caucasian female with acute exacerbation of chronic congestive heart failure who needed urgent Impella placement followed by elective Heartmate III LVAD. Conclusion: Patients who have aortic valve regurgitation at the time of implantation have been handled by several methods, including aortic valve leaflets approximation, to aortic valve replacement or even valve closure. We report a case of geometric ring annuloplasty for repair of a regurgitant aortic valve during destination LVAD implantation. [ABSTRACT FROM AUTHOR]

Uptake of the radiopharmaceutical F-FDG visualized by PET imaging can reflect abnormal myocardial inflammation. When utilized in conjunction with other imaging modalities, such as echocardiography, PET F-FDG imaging can help distinguish between active cardiac sarcoidosis and other etiologies of nonischemic cardiomyopathy. We present a case of a 46-year-old man with nonischemic cardiomyopathy and ventricular tachycardia who underwent an echocardiogram suggestive of cardiac Chagas disease. A subsequent F-FDG PET demonstrated abnormal hypermetabolism. The diagnosis was confirmed by positive serologic examination results.

Abstract Aims We sought to clarify the role of ventriculo–arterial (V–A) coupling in the treatment of nonischemic dilated cardiomyopathy (NIDCM) by adding a mineralocorticoid receptor antagonist (MRA) to conventional anti‐failure therapy. Methods and results We employed cardiac magnetic resonance imaging to quantify left ventricular (LV) contractility and V–A coupling in normal subjects at rest (n = 11) and in patients with NIDCM (n = 12) before and after long term anti‐failure therapy, in which MRA was added to conventional anti‐failure therapy. After ≥6 months' treatment in NIDCM patients, LV volumes and mass decreased, and the LV ejection fraction increased from a median of 24% (17, 27) (interquartile range IQR) to 47 (42, 52) (P 0.05). The V–A coupling ratio, Ea/end‐systolic elastance (single‐beat method), decreased by −1.08 (−1.96, −0.55), (P = 0.003), as did Ea/end‐systolic pressure/end‐systolic pressure ratio, −0.54 (0.35, 0.87), (P = 0.002). The preload recruitable stroke work (PRSW) increased as did PRSW indexed for Ea (both P = 0.002), which reflected ‘total circulatory performance’. Conclusions In NIDCM, adding MRA to conventional anti‐failure therapy markedly improved LV ejection fraction and reduced peripheral vascular resistance, due to both improved LV contractility and especially to enhanced V–A coupling, as Ea decreased to normal. Total circulatory performance was a sensitive indicator of both LV pump performance and the arterial loading conditions.

Left ventricular (LV) thrombus is not common but poses significant risks of embolic stroke or systemic embolism. However, the distinction in embolic risk between nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) remains unclear. In total, 2738 LV thrombus patients from the JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination) database were included. Among these patients, 1037 patients were analyzed, with 826 (79.7%) having ICM and 211 with NICM (20.3%). Within the NICM group, the distribution was as follows: dilated cardiomyopathy (DCM; 41.2%), takotsubo cardiomyopathy (27.0%), hypertrophic cardiomyopathy (18.0%), and other causes (13.8%). The primary outcome was a composite of embolic stroke or systemic embolism (SSE) during hospitalization. The ICM and NICM groups showed no significant difference in the primary outcome (5.8% vs. 7.6%, p = 0.34). Among NICM, SSE occurred in 12.6% of patients with DCM, 7.0% with takotsubo cardiomyopathy, and 2.6% with hypertrophic cardiomyopathy. Multivariate logistic regression analysis for SSE revealed an odds ratio of 1.4 (95% confidence interval [CI], 0.7–2.7, p = 0.37) for NICM compared to ICM. However, DCM exhibited a higher adjusted odds ratio for SSE compared to ICM (2.6, 95% CI 1.2–6.0, p = 0.022). This nationwide shows comparable rates of embolic events between ICM and NICM in LV thrombus patients, with DCM posing a greater risk of SSE than ICM. The findings emphasize the importance of assessing the specific cause of heart disease in NICM, within LV thrombus management strategies. • Of 1037 patients with LV thrombosis in the registry, 826 (79.7%) had ICM. • DCM is most common in NICM with LV thrombus. • There is no significant difference in embolic events between ICM and NICM. • DCM poses a higher risk of embolic events than ICM. [ABSTRACT FROM AUTHOR]

Background: Functional mitral regurgitation (FMR) in patients with cardiomyopathy is correlated with morbidity and mortality in heart failure. The response of FMR to cardiac resynchronization therapy (CRT) varies.Objectives: The purpose of this study was to analyze the incidence and severity of FMR in patients with nonischemic cardiomyopathy (NICM) and left bundle branch block (LBBB) and the response to left bundle branch pacing (LBBP).Methods: Patients who had undergone LBBP for NICM, LBBB, and FMR between 2019 to 2021 were included retrospectively in the study.Results: A total of 79 patients were identified, of whom 6 were excluded (5 no consistent LBB capture, 1 prosthetic mitral valve). The remaining 73 patients were divided into 2 groups based on the severity of FMR into group I with mild FMR (n = 35 [48%]) and group II with significant FMR (n = 38 [52%]). Mean follow-up duration was comparable in both groups. Group II was characterized by higher N-terminal pro-brain natriuretic peptide levels, New York Heart Association functional class, and larger left ventricular dimensions. LBBP resulted in significant reduction in QRS duration in both group I (113.8 ± 12.7 ms; P <.0001) and group II (117.3 ± 10.3 m s; P <.0001). LBBP resulted in similar percentage reduction in QRS duration (-31% ± 10% vs -33% ± 8%; P = .34), left ventricular (LV) end-diastolic diameter (-8% ± 10% vs -11% ± 12%; P = .25), LV end-diastolic volume (-26% ± 12% vs -31% ± 27%; P = .31), and LV end-systolic volume (-39% ± 16% vs -37% ± 30%; P = .72) in groups I and II, respectively. Percentage change (+59% ± 39% vs +59% ± 41%; P = 1) and absolute change (+19.9% ± 10.4% vs +17% ± 10.04%; P = .22) in LV ejection fraction were similar in both groups. In group II, 31 patients (82%) showed significant reduction in FMR severity during follow-up. No patients in group I showed worsening of FMR.Conclusion: LBBP resulted in excellent electrical resynchronization with significant reduction in FMR severity in the majority of patients with significant FMR and no worsening of FMR from baseline in any patient. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with arrhythmic events in patients with nonischemic cardiomyopathy (NICM), while others have questioned the role of left ventricular ejection fraction (LVEF) as a sole predictor of future events. Objectives: To evaluate the role of LGE on CMR in identifying patients with NICM and reduced LVEF for whom a benefit from defibrillator implantation for primary prevention is not anticipated, thus they are mainly exposed to potential risks. Methods: Major electronic databases were searched for studies reporting the incidence of appropriate device therapy (ADT), sudden cardiac death (SCD), and cardiac death based on the presence of LGE on CMR, among patients with NICM and reduced LVEF, implanted with a cardioverter defibrillator for primary prevention. Results: Eleven studies (1652 patients, 947 with LGE) were included in the final analysis. LGE presence was strongly associated with ADT (logOR: 1.95, 95%CI: 1.21–2.69) and cardiac death (logOR: 0.91, 95%CI: 0.14–1.68), but not with SCD (logOR: 0.26, 95%CI: −1.09–1.6). Diagnostic accuracy analysis demonstrated that contrast enhancement is a sensitive marker of future ADT and cardiac death (93%, 95%CI: 85.8–96.7%; 82.9%, 95%CI: 70.6–90.7%; respectively), with moderate specificity (44%, 95%CI: 27.2–62.6%; 37.7%, 95%CI: 23.4–54.6%; respectively). Conclusion: LGE is a highly sensitive predictor of ADT and cardiac death in NICM patients implanted with a defibrillator for primary prevention. However, due to moderate specificity, derivation of a cutoff with adequate predictive values and probably a multifactorial approach are needed to improve discrimination of patients who will not benefit from ICDs. [ABSTRACT FROM AUTHOR]

Background: Ventricular tachycardia (VT) substrate in left ventricular (LV) nonischemic cardiomyopathy (NICM) consists of fibrosis with surviving myocardium.Objective: The purpose of this study was to determine whether, in patients with LV NICM and sustained VT, reduced QRS amplitude and QRSf during sinus rhythm can identify the presence and location of abnormal septal (S-NICM) and/or free-wall (FW-NICM) VT substrate.Methods: We compared patients with NICM and VT (group 1) with electroanatomic mapping septal (S-NICM; n = 21) or free-wall (FW-NICM; n = 20) VT substrate to a 38-patient reference cohort (group 2) with cardiac magnetic resonance imaging (cMRI) and NICM but no VT referred for primary prevention implantable cardioverter-defibrillator (26 [68.4%] with late gadolinium enhancement).Results: Group 1 had lower QRS amplitude in leads II (0.60 ± 0.22 vs 0.86 ± 0.35, P <.001), aVR (0.60 ± 0.24 vs 0.75 ± 0.31, P = .002), aVF (0.48 ± 0.20 vs 0.70 ± 0.28, P <.001), and V2 (1.09 ± 0.52 vs 1.38 ± 0.55, P = .001) than group 2. QRS <0.55 mV in lead aVF identified VT and accompanying substrate with sensitivity 70% and specificity 71%. Most group 1 and group 2 patients had 12-lead ECG QRS fractionation (QRSf) in ≥2 contiguous leads (78% vs 63.2%, P = .14). Sensitivity and specificity for ≥2 QRSf leads identifying respective regional electroanatomic or cMRI abnormalities were 76% and 50% for inferior, 44% and 87% for lateral, and 21% and 89% for anterior leads.Conclusion: In LV NICM, low frontal plane QRS (<0.55 mV in aVF) is associated with VT substrate. Although multilead QRS fractionation is associated with the presence and location of VT substrate, it is frequently identified in patients without VT with cMRI abnormalities. [ABSTRACT FROM AUTHOR]

Background: Delays in diagnosis of peripartum cardiomyopathy (PPCM) are common and are associated with worse outcomes; however, few studies have addressed methods for improving early detection. Hypothesis: We hypothesized that easily accessible data (heart rate [HR] and electrocardiograms [ECGs]) could identify women with more severe PPCM and at increased risk of adverse outcomes. Methods: Clinical data, including HR and ECG, from patients diagnosed with PPCM between January 1998 and July 2016 at our institution were collected and analyzed. Linear and logistic regression were used to analyze the relationship between HR at diagnosis and the left ventricular ejection fraction (LVEF) at diagnosis. Outcomes included overall mortality, recovery status, and major adverse cardiac events. Results: Among 82 patients meeting inclusion criteria, the overall mean LVEF at diagnosis was 26 ± 11.1%. Sinus tachycardia (HR > 100) was present in a total of 50 patients (60.9%) at the time of diagnosis. In linear regression, HR significantly predicted lower LVEF (F = 30.00, p <.0001). With age‐adjusted logistic regression, elevated HR at diagnosis was associated with a fivefold higher risk of overall mortality when initial HR was >110 beats per minute (adjusted odds ratio 5.35, confidence interval 1.23–23.28), p =.025). Conclusion: In this study, sinus tachycardia in women with PPCM was associated with lower LVEF at the time of diagnosis. Tachycardia in the peripartum period should raise concern for cardiomyopathy and may be an early indicator of adverse prognosis. [ABSTRACT FROM AUTHOR]

Background: Patients with idiopathic nonischemic cardiomyopathy (NICM) and near-normal left ventricular ejection fraction (LVEF) may develop ventricular tachycardia (VT).Objective: The purpose of this study was to describe procedural characteristics and outcomes in patients requiring ablation for NICM-related VT with near-normal LVEF compared to impaired LVEF.Methods: Over 8 years, 77 consecutive patients with NICM-related VT underwent catheter ablation. Of these patients, 47 had idiopathic NICM (20 near-normal LVEF, 27 impaired LVEF). Procedural characteristics and outcomes were compared.Results: Mean age was 64 ± 12years, mean LVEF was 40% ± 14%, and 75% were male. In the near-normal LVEF group compared to the impaired LVEF group, LVEF was higher (54% ± 5% vs 30 ± 8%; P <.001), scar was predominantly located in the perivalvular left ventricle (LV) and basal septum (15/20 [75%]), was smaller in size [bipolar: 9.7 (6.2-32.4) cm2 vs 30.4 (21.1-37.6) cm2, P = .03; unipolar: 23.3 (6.6-39.9) cm2 vs 57.2 (42.2-74.9) cm2, P = .009], and required smaller areas of ablation [7.0 (5.9-14.2) cm2 vs 11.4 (8.5-16.7) cm2, P = .06]. Both groups experienced comparable procedure times, fluoroscopy doses, ablation times, VT cycle lengths, and acute success rates. After final ablation, VA-free survival was comparable between both groups (65% vs 63%; P = .63) at 12 months.Conclusion: Idiopathic NICM-related VT with near-normal LVEF was associated with discrete areas of arrhythmogenic, predominantly intramural, scar in the perivalvular LV and basal septum. Despite smaller scar, patients required similar ablation amounts and experienced comparable long-term outcomes compared to patients with idiopathic NICM-related VT and impaired LVEF. These findings underscore the "three-dimensionality" of substrate, whereby the intramural basal septum forms the third dimension and impacts ablation outcomes. [ABSTRACT FROM AUTHOR]