Nonischemic or Dual Cardiomyopathy in Patients With Coronary Artery Disease.

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

Septal late enhancement by cardiac CT is associated with repeat ablation in nonischemic cardiomyopathy patients.

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.

Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis.

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.

Left atrial conduit strain derived from cardiac magnetic resonance is an independent predictor of left ventricular reverse remodeling in patients with nonischemic cardiomyopathy.

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 < 0.001). The multivariate logistic regression analysis showed that LA conduit strain was an independent predictor of LVRR (odds ratio [OR]: 1.216, 95% confidence interval [CI]: 1.050-1.408; p = 0.009). The area under the receiver operating characteristic (ROC) curve of the LA conduit strain was 0.746, and the cutoff value was 6.2%. The Kaplan‒Meier analysis revealed that the incidence of adverse cardiac events was significantly lower in patients with LA conduit strain > 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.

The Uncertain Benefit from Implantable Cardioverter-Defibrillators in Nonischemic Cardiomyopathy: How to Guide Clinical Decision-Making?

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.

Ripple mapping in ventricular tachycardia substrate mapping and ablation of nonischemic ventricular tachycardia.

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.

Value of genotyping and scar-phenotyping for VT ablation procedures in patients with nonischemic left ventricular cardiomyopathies.

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.

Heart Failure With Recovered Ejection Fraction in Patients With Nonischemic Cardiomyopathy: Characteristics, Outcomes, and Long-term Follow-up.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Viral Myocarditis and Dilated Cardiomyopathy as a Consequence-Changing Insights from Advanced Imaging.

Advancements in quantitative cardiac magnetic resonance (CMR) have revolutionized the diagnosis and management of viral myocarditis. With the addition of T1 and T2 mapping parameters in the updated Lake Louise Criteria, CMR can diagnose myocarditis with superior diagnostic accuracy compared with endomyocardial biopsy, especially in stable patients. Additionally, the unique value of CMR tissue characterization continues to improve the diagnosis and risk stratification of myocarditis. This review will discuss new and ongoing developments in cardiovascular imaging and its application to noninvasive diagnosis, prognostication, and management of viral myocarditis and its complications.

Contemporary Application of Cardiovascular Magnetic Resonance Imaging.

Cardiovascular magnetic resonance imaging (CMR) is a comprehensive and versatile diagnostic and prognostic imaging modality that plays an increasingly important role in management of patients with cardiovascular disease. In this review, we discuss CMR applications in nonischemic cardiomyopathy, ischemic heart disease, arrhythmias, right ventricular diseases, and valvular heart disease. We emphasize the quantitative nature of CMR in current practice, from volumes, function, myocardial strain analysis, and late gadolinium enhancement to parametric mapping, including T1, T2, and T2* relaxation times and extracellular volume fraction assessment.

Temporal Trends in the Incidence and Characteristics of Sudden Cardiac Death among Subjects under 40 Years of Age in Northern Finland during 1998-2017.

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.

Concomitant aortic valve repair for aortic insufficiency and implantation of left ventricle mechanical support.

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.

Risk Prediction for Peripartum Cardiomyopathy in Delivering Mothers: A Validated Risk Model: PPCM Risk Prediction Model.

BACKGROUND: Peripartum cardiomyopathy (PPCM) causes significant morbidity and mortality in childbearing women. Delays in diagnosis lead to worse outcomes; however, no validated risk prediction model exists. We sought to validate a previously described model and identify novel risk factors for PPCM presenting at the time of delivery. METHODS AND RESULTS: Administrative hospital records from 5,277,932 patients from 8 states were screened for PPCM, identified by International Classification of Disease-9 Clinical Modification codes (674.5x) at the time of delivery. Demographics, comorbidities, procedures, and outcomes were quantified. Performance of a previously published regression model alone and with the addition of novel PPCM-associated characteristics was assessed using receiver operating characteristic area under the curve (AUC) analysis. Novel risk factors were identified using multivariate logistic regression and the likelihood ratio test. In total, 1186 women with PPCM were studied, including 535 of 4,003,912 delivering mothers (0.013%) in the derivation set compared with 651 of 5,277,932 (0.012%) in the validation set. The previously published risk prediction model performed well in both the derivation (area under the curve 0.822) and validation datasets (area under the curve 0.802). Novel PPCM-associated characteristics in the combined cohort included diabetes mellitus (odds ratio [OR] of PPCM 1.93, 95% confidence interval [CI] 1.23-3.02, P = .004), mood disorders (OR 1.74, 95% CI 1.22-2.47, P = .002), obesity (OR 1.92, 95% CI 1.45-2.55, P < .001), and Medicaid insurance (OR 1.54, 95% CI 1.22-1.96, P < .001). CONCLUSIONS: This is the first validated risk prediction model to identify women at increased risk for PPCM at the time of delivery. Diabetes mellitus, obesity, mood disorders, and lower socioeconomic status are risk factors associated with PPCM. This model may be useful for identifying women at risk and preventing delays in diagnosis.

A model for continued LVAD patient success: A 4-year readmission-free HeartMate 3 postoperative course.

Unplanned readmissions frequently occur following the implantation of a durable left ventricular assist device (LVAD) due to complications such as gastrointestinal bleeding and driveline infection. There is a paucity of literature describing the incidence of unplanned readmission in patients with a HeartMate 3 (HM3) Left Ventricular Assist System. In this report, we present the successful outcome of a patient with an HM3 LVAD who has experienced no unplanned readmissions in the 4-year post-implant phase. To our knowledge, this is the longest readmission-free case after HM3 implantation. A successful patient outcome was enabled by the use of the modular HM3 device, the postoperative prescription of beta-blockers and omega-3, the presence of strong social support, and open communication between the patient's caregivers and the LVAD team. Reducing the instance of unplanned readmission confers clinical benefits to the patient, as well as reducing the cost burden on the patient and the healthcare system.

Global longitudinal strain evaluated by speckle-tracking echocardiography as a surrogate marker for predicting replacement fibrosis detected by magnetic resonance-late gadolinium enhancement in patients with nonischemic cardiomyopathy.

PURPOSE: This study aimed to investigate whether left ventricular (LV) global longitudinal strain (GLS) evaluated by speckle-tracking echocardiography (STE) can be used as a surrogate marker for the detection of replacement fibrosis by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) in patients with nonischemic cardiomyopathy (NICM). METHODS: This study analyzed 41 NICM patients who successfully underwent both STE and CMR, and were divided into those with (Group A, n = 18) and those without CMR-LGE (Group B, n = 23). Echocardiographic indexes, including GLS, were compared between the two groups. RESULTS: No significant differences were observed in LV end-diastolic and end-systolic volume indexes, LV ejection fraction, mitral E/A, deceleration time, E/e', left atrial volume index, and the systolic trans-tricuspid pressure gradient between Groups A and B. STE-GLS was significantly worse in Group A than in Group B (-7.6% ± 3.0% vs -9.9% ± 3.2%, P = .01). Receiver operating characteristic curve analysis showed that STE-GLS of -7.9% was the best cut-off value for detection of CMR-LGE (sensitivity, 78%; specificity, 74%; and area under the curve, 0.74). CONCLUSIONS: STE-GLS may be a potential surrogate marker for the detection of CMR-LGE-derived replacement fibrosis in patients with NICM.

Collateral injury of the conduction system during catheter ablation of septal substrate in nonischemic cardiomyopathy.

INTRODUCTION: In patients with nonischemic cardiomyopathy (NICM) little is known about the clinical impact of catheter ablation (CA) of septal ventricular tachycardia (VT) resulting in the collateral injury of the conduction system (CICS). METHODS AND RESULTS: Ninety-five consecutive patients with NICM underwent CA of septal VT. Outcomes in patients with no baseline conduction abnormalities who developed CICS (group 1, n = 28 [29%]) were compared to patients with no CICS (group 2, n = 17 [18%]) and to patients with preexisting conduction abnormalities or biventricular pacing (group 3, n = 50 [53%]). Group-1 patients were younger, had a higher left ventricular ejection fraction and a lower prevalence of New York Heart Association III/IV class compared to group 3 while no significant differences were observed with group 2. After a median follow-up of 15 months, VT recurred in 14% of patients in group 1, 12% in group 2 (P = .94) and 32% in group 3 (P = .08) while death/transplant occurred in 14% of patients in group 1, 18% in group 2 (P = .69) and 28% in group 3 (P = .15). A worsening of left ventricular ejection fraction (LVEF) (median LVEF variation, -5%) was observed in group 1 compared to group 2 (median LVEF variation, 0%; P < .01) but not group-3 patients (median LVEF variation, -4%; P = .08) with a consequent higher need for new biventricular pacing in group 1 (43%) compared to group 2 (12%; P = .03) and group 3 (16%; P < .01). CONCLUSIONS: In patients with NICM and septal substrate, sparing the abnormal substrate harboring the conduction system provides acceptable VT control while preventing a worsening of the systolic function.

Association of septal late gadolinium enhancement on cardiac magnetic resonance with ventricular tachycardia ablation targets in nonischemic cardiomyopathy.

BACKGROUND: Ablation of septal substrate-associated ventricular tachycardia (VT) in patients with nonischemic cardiomyopathy (NICM) is challenging. We sought to standardize the characterization of septal substrates on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) and to examine the association of that substrate with VT exit and isthmus sites on invasive mapping. METHODS: LGE-CMR was performed before electroanatomic mapping and ablation for VT in 20 NICM patients. LGE extent and distribution were quantified using myocardial signal-intensity Z scores (SI-Z). The SI-Z thresholds correlating to previously validated voltage thresholds, for abnormal tissue and dense scar were defined. RESULTS: Bipolar and unipolar (electrogram) voltage amplitude measurements from the LV and RV were negatively associated with SI-Z from LGE-CMR imaging (p < .05). SI-Z thresholds for appropriate CMR identification of septal substrates were determined to be greater than -.15 for border zone and greater than .03 for a dense scar. Among all patients, 34 critical VT sites were identified with SI-Z distribution in the range of -.97 to .06. Thirty (88.2%) critical sites were located in the dense LGE, 1 (2.9%) in the border zone, and 3 (8.9%) in healthy tissue but within 7 mm of LGE. Of note, critical VT sites were all located at the basal septum close to valves (distance to aortic valve: 17.5 ± 31.2 mm, mitral valve: 21.2 ± 8.7 mm) in nonsarcoidosis cases. CONCLUSIONS: Critical sites of septal VT in NICM patients are predominantly in the CMR defined dense scar when using standardized signal-intensity thresholds.

Characteristics of ventricular tachyarrhythmias and their susceptibility to antitachycardia pacing termination in patients with ischemic and nonischemic cardiomyopathy: A patient-level meta-analysis of three large clinical trials.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce all-cause mortality among cardiomyopathy patients. Whether or not antitachycardia pacing (ATP) is equally effective in ischemic (ICM) and nonischemic (NICM) cardiomyopathy patients remains poorly understood. We describe the distribution of monomorphic (MVT) and non-monomorphic (polymorphic ventricular tachycardia/ventricular fibrillation [PVT/VF]) ventricular tachyarrhythmias among ICM and NICM primary prevention patients. METHODS: This patient-level meta-analysis included primary prevention patients from the Shock-Less (n = 3519), PainFree SST (n = 1917), and PREPARE (n = 690) studies. Distribution of MVT and PVT/VF events were compared with χ2 tests. ATP success was estimated using a generalized estimating equation model to correct for multiple episodes for a patient between cohorts for slow (≥320 ms) and fast (240-310 ms) MVTs. RESULTS: Among 6126 patients, 714 (29% NICM, age 66 ± 13 years, female 18%, EF = 29 ± 12%) had a total of 4444 treated ventricular tachyarrhythmia episodes. The rate of individuals treated for MVT or PVT/VF was comparable between ICM (11.9%) and NICM (11.2%) over 21 ± 10 months. In addition, the distribution of MVT (76% ICM vs. 71% NICM) and PVT/VF (15% ICM vs. 20% NICM) was not significantly different (p = .28). Among MVT episodes, the average tachycardia cycle lengths (332 ± 58 ms ICM vs. 313 ± 40 ms NICM; p = .27) were similar, as was the likelihood of ATP-associated termination (74.6% ICM vs. 76.4% NICM; p = .58). Overall, ATP success was higher for slow (≥320 ms) MVT versus faster (240-310 ms) episodes (84.1% vs. 69%; p < .001). CONCLUSION: In a large cohort of primary prevention ICD patients, ICM and NICM patients have similar rates and proportions of MVT and PVT/VF episodes. ATP-associated termination of MVT was comparable between the two groups.

His-bundle pacing: A novel treatment for left bundle branch block-mediated cardiomyopathy.

BACKGROUND: Chronic left bundle branch block (LBBB) can lead to LBBB-mediated cardiomyopathy from left ventricular dysynchrony. His-bundle pacing (HBP) results in direct electrical synchrony using the native His-Purkinje system, providing a novel treatment for this cardiomyopathy. OBJECTIVE: To assess the feasibility of HBP for cardiac resynchronization therapy (CRT) in LBBB-mediated cardiomyopathy patients. METHODS: Retrospective database review was conducted on patients who underwent CRT by the HBP capable provider at Indiana University Health and Eskenazi Hospital from August 2015 to August 2017. A subset of patients who met the predefined syndrome criteria of LBBB-mediated cardiomyopathy who underwent HBP were identified. Clinical, echocardiographic, and electrocardiographic variables were extracted at baseline and follow-up. RESULTS: Nine patients had cardiomyopathy and LBBB. Among those two were lost to follow-up. Seven patients were included in the analysis. The average time from device implantation to the last follow-up was 14.5 months. Left ventricular ejection fraction improved on average from 25% to 50% (p = .0001). The left ventricular end-systolic dimension decreased from 47 to 37 mm (p = .003) and the left ventricular end-diastolic dimension decreased from 55 to 48 mm (p = .03). QRS duration with HBP-CRT decreased from 152 to 115 ms. New York Heart Association classification improved from an average of 2.7-2. CONCLUSION: HBP is a viable technique for pursuing CRT in patients with LBBB-mediated cardiomyopathy.

Positron emission tomography absolute stress myocardial blood flow for risk stratification in nonischemic cardiomyopathy.

INTRODUCTION: Sudden cardiac death is a substantial cause of mortality in patients with cardiomyopathy, but evidence supporting implantable cardioverter-defibrillator (ICD) implantation is less robust in nonischemic cardiomyopathy (NICM) than in ischemic cardiomyopathy. Improved risk stratification is needed. We assessed whether absolute quantification of stress myocardial blood flow (sMBF) measured by positron emission tomography (PET) predicts ventricular arrhythmias (VA) and/or death in patients with NICM. METHODS: In this pilot study, we prospectively followed patients with NICM (left ventricular ejection fraction ≤ 35%) and an ICD who underwent cardiac PET stress imaging with sMBF quantification. NICM was defined as the absence of angiographic obstructive coronary stenosis, significant relative perfusion defects on imaging, coronary revascularization, or acute coronary syndrome. Endpoints were appropriate device therapy for VA and all-cause mortality. Subgroup analysis was performed in patients who had no prior history of VA (ie, the primary prevention population). RESULTS: We followed 37 patients (60 ± 14 years, 46% male) for 41 ± 23 months. The median sMBF was 1.56 mL/g/min (interquartile range: 1.00-1.82). Lower sMBF predicted VA, both in the whole population (hazard ratio [HR] for each 0.1 mL/g/min increase: 0.84, P = .015) and in the primary prevention subset (n = 27; HR for each 0.1 mL/g/min increase: 0.81, P = .049). Patients with sMBF below the median had significantly more VA than those above the median, both in the whole population (P = .004) and in the primary prevention subset (P = .046). Estimated 3-year VA rates in the whole population were 67% among low-flow patients vs 13% among high-flow patients, and 39% vs 8%, respectively, among primary-prevention patients. sMBF did not predict all-cause mortality. CONCLUSIONS: In patients with NICM, lower sMBF predicts VA. This relationship may be useful for risk stratification for ventricular arrhythmia and decision making regarding ICD implantation.