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Objective: Examine the trajectory of left ventricular ejection fraction (EF) among patients eligible for implantable cardioverter-defibrillator (ICD) therapy Background: Ejection fraction is the cornerstone criterion for ICD therapy, but the risk of sudden cardiac death (SCD) remains after an improvement in EF. Methods: We examined the trajectory of EF among 1178 participants of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) who had 3 or more assessments of EF, at least 90 days apart. A follow-up EF >35% or >10% absolute increase in EF from baseline were examined as the criteria for EF improvement. Results: At first follow-up, 381 (32%) patients had an improvement of EF to >35%. However, EF had returned back to 35% in 109 (27%) of these patients at second follow-up. Similarly, 446 (38%) patients experienced a >10% improvement in EF at first follow-up, but 109 (24%) of these had a subsequent >10% decrease in EF at the second follow-up. Of the 32 patients with normalized EF (≥55%) at first follow-up, 18 (56%) had a subsequent >10% decrease in EF. The fluctuation in EF was present in both ischemic and non-ischemic cardiomyopathy but a higher proportion of patients with non-ischemic cardiomyopathy had an improvement in EF to >35% at first follow-up compared to those with ischemic cardiomyopathy (38% vs. 27%, p=

Objectives The goal of this study was to investigate the relationship between cardiac scar on late gadolinium enhancement cardiac resonance imaging (LGE-CMR) and the presence of ventricular tachycardia (VT) ablation target sites within the sinuses of Valsalva (SV). Background Patients with idiopathic dilated cardiomyopathy (IDCM) often have scarring involving the basal myocardium, including the SV, allowing targeting of VTs from within the SV. Methods Forty-three consecutive patients with IDCM underwent a VT ablation procedure with pre-procedure LGE-CMR. Retrospectively, scar characteristics were compared between patients with and without VT target sites in the SV. The ratio between SV-related scarring and the total cardiac scarring was defined as the SV scar index: SV-related scarring/total cardiac scarring. Results VT target sites were identified in the SV in 22 (51%) of 43 patients. LGE-CMR identified peri-aortic scarring involving the SV in 34 patients (79%). Scarring extended to the septum in 26 patients, involved the lateral basal wall in 4, and both areas in 13 patients. Scar volume within the SV was larger in patients with SV-VT targets (1.7 ± 0.9 cm3 vs. 0.7 ± 0.6 cm3; p Conclusions Patients with IDCM undergoing ablation of VT often have peri-aortic scarring visualized on LGE-CMR. Both the presence and the extent of scarring adjacent to the aortic annulus are associated with the presence of VT target sites within the SV.

Introduction: We have described previously an arrhythmic mechanism in nonischemic heart failure (NI-HF) involving an increased mitochondrial Ca 2+ uptake that results in QT prolongation and lethal arrhythmias. This arrhythmic mechanism is associated with mitochondrial Ca 2+ uniporter (MCU) tyrosine phosphorylation (p-Tyr). Hypothesis: Here, we determined which kinase was responsible for MCU phosphorylation in cardiomyopathy. Methods: NI-HF was induced by hypertension in Wt C57BL6 mice by unilateral nephrectomy, deoxycorticosterone acetate (DOCA) treatment and substituting drinking water with 1% saline for six weeks. Western blot, immunoprecipitation, fluorescence resonance energy transfer (FRET) and patch-clamp techniques were employed in isolated mouse cardiomyocytes. Results: When compared to control hearts, the protein level of p-Src S17 increased significantly accompanied by significant enhancement of tyrosine but not serine/threonine phosphorylation of MCU in NI-HF mouse hearts. In a heterologous expression system, c-Src could bind MCU and tyrosine phosphorylate MCU. This phosphorylation was blocked by a c-Src inhibitor, PP1. Overexpression of constitutive active c-Src (Src-Y527F) significantly increased MCU inward current at -160 mV. It suggested that c-Src activation was directly related to mitochondrial-mediated arrhythmic risk. Downregulation of C-terminal Src kinase (CSK), a regulatory kinase inversely related to c-Src activity, increased p-Src, enhanced mitochondrial and SR contact, and facilitated mitochondrial Ca 2+ uptake in NI-HF mouse cardiomyocytes. Proline-rich tyrosine kinase 2 (Pyk2) did not contribute more phosphorylated MCU during cardiomyopathy as the protein expression of PyK2, p-PyK2 Y402 and p-PyK2 Y579/580 did not change during NI-HF. Correlation using human heart tissue showed that NI-HF patients had significantly increased p-Src S17 associated with an increased incidence of QTc elongation and arrhythmia. Conclusions: During cardiomyopathy, c-Src activation directly tyrosine phosphorylated MCU, increased MCU current, and increased mitochondrial/SR contact, suggesting this kinase is responsible for the increase in mitochondria-mediated arrhythmic risk seen in NI-HF.

Objectives This study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM). Background The presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information. Methods Cardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. Results During a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p, Central Illustration

Background Randomized control trials comparing the effectiveness of cardiac resynchronization therapy devices, with (CRT-D) or without (CRT-P) a defibrillator, are scarce in heart failure patients. Patients with nonischemic dilated cardiomyopathy (NICM) may be at lower risk for ventricular arrhythmias compared with those with ischemic cardiomyopathy. In addition, NICM has been identified as a predictor of positive response to CRT. The aim of this study was to investigate the impact of an additional implantable cardioverter-defibrillator over CRT in Korean patients with NICM. Methods During the period from January 1, 2008 to December 31, 2017, 533 NICM patients (mean age, 65.7±12.2 years, male 53.6%) with newly-implanted CRT-P (n=71) or CRT-D (n=462) who were aged 19 years or older were identified by 50-percents random sampling from the Korean National Health Insurance Service database. Results Compared with patients receiving CRT-P, those receiving CRT-D were younger (65.3±12.3 vs. 68.3±11.6 years, p=0.038), more likely to be male (56.1% vs. 38.0%, p=0.005), and have an admission history of congestive heart failure (93.9% vs. 87.3%, p=0.041). Over the mean follow-up period of 21 months,114 cases in the CRT-D group and 24 cases in the CRT-P group died, with annualized mortality rates of 14.9 and 17.2 per 100 person-years, respectively. Kaplan-Meier estimates of event-free survival showed that there was no difference in mortality between CRT-D and CRT-P groups (p=0.343). In multivariate analysis, factors associated with mortality were chronic kidney disease, atrial fibrillation, and older age. With regard to death or heart failure hospitalization, heart failure death, and non-cardiac death, there were no difference between the two groups. Conclusions Among Asian patients with NICM with indications for CRT, death, death or heart failure hospitalization, heart failure death, and non-cardiac death were not different between CRT-D and CRT-P groups. Funding Acknowledgement Type of funding source: None

Background In patients with nonischemic cardiomyopathy, nonischemic fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is related to adverse cardiovascular outcomes. However, its relationship with left ventricular (LV) mechanical deformation parameters remains unclear. We sought to investigate the association between LV mechanics and the presence, location, and extent of fibrosis in patients with nonischemic cardiomyopathy. Methods and Results We retrospectively identified 239 patients with nonischemic cardiomyopathy (67% male; 55±14 years) referred for a clinical cardiovascular magnetic resonance. LGE was present in 109 patients (46%), most commonly (n=52; 22%) in the septum. LV deformation parameters did not differentiate between LGE‐positive and LGE‐negative groups. Global longitudinal, radial, and circumferential strains, twist and torsion showed no association with extent of fibrosis. Patients with septal fibrosis had a more depressed LV ejection fraction (30±12% versus 35±14%; P =0.032) and more impaired global circumferential strain (−7.9±3.5% versus −9.7±4.4%; P =0.045) and global radial strain (10.7±5.2% versus 13.3±7.7%; P =0.023) than patients without septal LGE. Global longitudinal strain was similar in both groups. While patients with septal‐only LGE (n=28) and free wall–only LGE (n=32) had similar fibrosis burden, the septal‐only LGE group had more impaired LV ejection fraction and global circumferential, longitudinal, and radial strains (all P Conclusions There is no association between LV mechanical deformation parameters and presence or extent of fibrosis in patients with nonischemic cardiomyopathy. Septal LGE was associated with poor global LV function, more impaired global circumferential and radial strains, and more impaired global strain rates.

Background Coronavirus Disease‐2019 (COVID‐19) has been associated with myocardial injury and higher risk of arrhythmic complications. However, no reports are available about the effect of the ongoing pandemic on arrhythmias in patients at risk. Objective To describe the effect of COVID‐19 pandemic on arrhythmic burden among high‐risk patients. Methods This is a cross‐sectional study on the incidence of ventricular arrhythmia (VA) during the pandemic outbreak (study period), compared to the same timeframe in 2019 (reference period). Inclusion criteria were age (>18 years) and having an implantable cardiac defibrillator (ICD). Results Among 455 patients enrolled (mean age 64.9 ± 15.7 years; 25.1% females and 39.6% with CRTD), in the study period, 45 (9.9%) patients experienced a total of 86 VA; 8 patients (1.7%) required antitachycardia‐pacing (ATP) and 6 (1.3%) at least one shock. In the reference period, a total of 69 events occurred in 36 patients (7.9%). Six patients (1.3%) required ATP and three (0.7%) at least one shock. The number of patients that suffered from any arrhythmic events in the study period (9.9% vs 7.9%) did not significantly differ from the reference period (χ2 = 1.09, P = .29). The main predictor of VA during the COVID‐19 pandemic was the previous history of any ICD therapy (OR = 3.84, P, Among 455 patients (mean age 64.9 ± 15.7 years), 25.1% were females and 39.6% had a CRTD. The number of patients that suffered from any arrhythmic events in the study period (9.9 vs 7.9%) did not significantly differ from the reference period (χ2 = 1.09, P = .29). No evidence of an increase of arrhythmic burden was found during the COVID‐19 epidemic.

Background Outcomes data in patients with cardiac amyloidosis after implantable cardioverter‐defibrillator (ICD) implantation are limited. We compared outcomes of patients with ICDs implanted for cardiac amyloidosis versus nonischemic cardiomyopathies (NICMs) and evaluated factors associated with mortality among patients with cardiac amyloidosis. Methods and Results Using National Cardiovascular Data Registry’s ICD Registry data between April 1, 2010 and December 31, 2015, we created a 1:5 propensity‐matched cohort of patients implanted with ICDs with cardiac amyloidosis and NICM. We compared mortality between those with cardiac amyloidosis and matched patients with NICM using Kaplan‐Meier survival curves and Cox proportional hazards models. We also evaluated risk factors associated with 1‐year mortality in patients with cardiac amyloidosis using multivariable Cox proportional hazards regression models. Among 472 patients with cardiac amyloidosis and 2360 patients with propensity‐matched NICMs, 1‐year mortality was significantly higher in patients with cardiac amyloidosis compared with patients with NICMs (26.9% versus 11.3%, P 2.5 (HR, 4.34; 95% CI, 2.72–6.93). Conclusions Mortality after ICD implantation is significantly higher in patients with cardiac amyloidosis than in patients with propensity‐matched NICMs. Factors associated with death among patients with cardiac amyloidosis include prior syncope, ventricular tachycardia, cerebrovascular disease, diabetes mellitus, and impaired renal function.

In patients with nonischemic cardiomyopathy, epicardial ablation is critical in targeting epicardial paravalvular substrate. Epicardial access and ablation can be performed safely with attention to epicardial structures, such as the coronary arteries, phrenic nerve, and epicardial fat. This review explores the indications, techniques, complications, and outcomes of epicardial ablation in patients with nonischemic cardiomyopathy. Although epicardial ablation adds to the complexity and risk of the ablation procedure, it is a vital tool that, combined with endocardial mapping and ablation, improves outcomes in patients with nonischemic cardiomyopathy suffering from ventricular arrhythmias.

Introduction The association of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) with epicardial and surface ventricular tachycardia (VT) electrogram features, in nonischemic cardiomyopathy (NICM), is unknown. We sought to define the association of LGE and viable wall thickness with epicardial electrogram features and exit site paced QRS duration in patients with NICM. Methods A total of 19 patients (age 53.5 +/- 11.5 years) with NICM (ejection fraction 40.2 +/- 13.2%) underwent CMR before VT ablation. LGE transmurality was quantified on CMR and coregistered with 2294 endocardial and 2724 epicardial map points. Results Both bipolar and unipolar voltage were associated with transmural signal intensity on CMR. Longer electrogram duration and fractionated potentials were associated with increased LGE transmurality, but late potentials or local abnormal ventricular activity were more prevalent in nontransmural versus transmural LGE regions (p < .05). Of all critical VT sites, 19% were located adjacent to regions with LGE but normal bipolar and unipolar voltage. Exit site QRS duration was affected by LGE transmurality and intramural scar location, but not by wall thickness, at the impulse origin. Conclusions In patients with NICM and VT, LGE is associated with epicardial electrogram features and may predict critical VT sites. Additionally, exit site QRS duration is affected by LGE transmurality and intramural location at the impulse origin or exit.

Introduction Testing for inducible ventricular tachycardia (VT) pre- and postablation forms the cornerstone of contemporary scar-related VT ablation procedures. There is significant heterogeneity in reported VT induction protocols. We examined the utility of an extensive induction protocol (up to 4 extra-stimuli [ES] ± burst ventricular pacing) compared to the current guideline-recommended protocol (up to 3ES, defined as limited induction protocol) in patients with scar-related VT. Methods and results Sixty-two patients (age: 64 ± 14 years; left ventricular ejection fraction: 37 ± 13%, ischemic cardiomyopathy: 31, nonischemic cardiomyopathy: 31) with at least one inducible VT were included. An extensive testing protocol induced 11%-17% more VTs, compared to the limited induction protocol before, and after the final ablation. VT recurred in 48% of patients during a mean follow up of 566 ± 428 days. Patients who were noninducible for any VT using the limited induction protocol had worse ventricular arrhythmia (VA)-free survival (12 months, 43% vs. 82%; p = .03) and worse survival free of VA, transplantation and mortality (12 months 46% vs. 82%; p = .02), compared to patients who were noninducible for any VT using the extensive induction protocol. Conclusions Between 11% and 17% of inducible VTs may be missed if 4ES and burst pacing are not performed in induction protocols before and after ablation. Noninducibility for any VT after an extensive induction protocol after the final ablation portends more favorable prognostic outcomes when compared with the current guideline-recommended induction protocol of up to 3ES. This data suggests that the adoption of an extensive induction protocol is of prognostic benefit after VT ablation.

Background The underlying substrates and mechanisms of non-sustained ventricular tachycardia (NSVT) in nonischemic dilated cardiomyopathy (DCM) are unclear and may be different than those of sustained VT. Purpose To characterize NSVT in DCM and analyze its association with late gadolinium enhancement (LGE) on CMR, inducibility of sustained VT during EP study, and ventricular arrhythmias during follow-up. Methods In the prospective Leiden Nonischemic Cardiomyopathy Study (ClinicalTrials.gov Identifier: NCT01940081) patients with DCM underwent a comprehensive evaluation. For the present study, 24h-Holters were assessed for the presence of NSVT (defined as ≥3 consecutive beats arising below the atrioventricular node with a rate ≥120 bpm and lasting 10%, duration, coupling interval and morphology). CMRs were assessed for the presence of LGE and EP studies for inducibility of sustained monomorphic VT. Patients were followed and ICDs were programmed with therapy >188-200 bpm or adjusted to clinically documented VT. Results Of all 148 patients, 95 underwent a 24-hour Holter at the Leiden University Medical Center and were included in the present study (age 59 ± 13 years, 76% male, history of sustained VT in 26 [27%], out-of-hospital cardiac arrest in 7 [9%]). NSVT was observed during Holter in 52 patients (55%) and was typically short (median 4 beats, IQR 3-5 beats), relatively slow (median 144 bpm, IQR 134-156 bpm), irregular (median 67%, IQR 43-100% of all episodes per patient) and monomorphic (median 87%, IQR 12-100%). NSVT was not associated with LGE on CMR (p = 0.49) or VT inducibility during EP study (p = 0.96), nor were its features (all p > 0.05). During 4.0 ± 1.7 years follow-up, sustained VT occurred in 25 patients (26%), polymorphic VT/VF in 8 (8%), and any sustained ventricular arrhythmia in 30 (32%). NSVT was associated with a higher rate of sustained VT during follow-up (HR 5.45, p = 0.002) and any sustained ventricular arrhythmia (HR 4.17, p = 0.002), but not with polymorphic VT/VF (p = 0.69). Similarly, inducibility of sustained VT during EP study was also associated with sustained VT during follow-up (HR 5.78, p Conclusion In DCM, NSVT on Holter and inducible sustained VT during EP study are not directly interrelated, but both predict the occurrence of sustained VT during follow-up. These data suggest that non-sustained and sustained VT may have different underlying mechanisms and provide complementary information in DCM. Abstract Figure. Sustained VT during follow-up

Background Previous studies have reported inconsistent results on the relationship between body mass index (BMI) and clinical outcomes in implantable cardioverter defibrillator (ICD) patients. Additionally, research on ICD patients with nonischemic cardiomyopathy (NICM) is lacking. Hypothesis This study aimed to investigate the impact of BMI on mortality and ventricular arrhythmias (VAs) in NICM patients with an ICD. Methods This study retrospectively analyzed the data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device‐implanted patients (SUMMIT) in China. Four hundred and eighty NICM patients with an ICD having BMI data were enrolled. Patients were divided into two groups: underweight and normal range group (BMI

We describe a case of a 65-year-old gentleman with nonischemic cardiomyopathy and left bundle branch block who underwent cardiac resynchronization therapy device. After becoming a responder initially, he experienced significant clinical worsening on follow-up. Device interrogation revealed several long episodes of inappropriate automatic mode switch (AMS) entry due to far-field R wave oversensing resulting in loss of atrioventricular synchrony. Moreover, pacing in VVI mode with consistent VA conduction taking place during the AMS episodes was also found to be detrimental, which helped in sustaining the episodes and produced pacemaker syndrome like phenomenon. Attempts made to resolve the issue by prolonging the post-ventricular atrial blanking period was unsuccessful, hence we adjusted the atrial channel sensitivity to troubleshoot the problem.

Friedreich’s ataxia (FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical manifestations of FRDA include ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases. However, the broad clinical spectrum makes FRDA difficult to identify. The diagnosis of FRDA is based on the presence of suspicious clinical factors, the use of the Harding criteria and, more recently, the use of genetic testing for identifying the expansion of a triplet nucleotide sequence. FRDA is linked to a defect in the mitochondrial protein frataxin; an epigenetic alteration interferes with the folding of this protein, causing a relative deficiency of frataxin in affected patients. Frataxins are small essential proteins whose deficiency causes a range of metabolic disturbances, including oxidative stress, iron-sulfur cluster deficits, and defects in heme synthesis, sulfur amino acid metabolism, energy metabolism, stress responses, and mitochondrial function. The cardiac involvement seen in FRDA is a consequence of mitochondrial proliferation as well as the loss of contractile proteins and the subsequent development of myocardial fibrosis. The walls of the left ventricle become thickened, and different phenotypic manifestations are seen, including concentric or asymmetric hypertrophy and (less commonly) dilated cardiomyopathy. Dilated cardiomyopathy and arrhythmia are associated with mortality in patients with FRDA, whereas hypertrophic cardiomyopathy is not. Systolic function tends to be low-normal in FRDA patients, with an acute decline at the end of life. However, the literature includes only a few long-term prospective studies of cardiac progression in FRDA, and the cause of death is often attributed to heart failure and arrhythmia postmortem. Cardiomyopathy tends to be correlated with the clinical neurologic age of onset and the nucleotide triplet repeat length (i.e., markers of phenotypic disease severity) rather than the duration of disease or the severity of neurologic symptoms. As most patients are wheelchair-bound within 15 years of diagnosis, the clinical determination of cardiac involvement is often complicated by comorbidities. Researchers are currently testing targeted therapies for FRDA, and a centralized database, patient registry, and natural history study have been launched to support these clinical trials. The present review discusses the pathogenesis, clinical manifestations, and spectrum of cardiac disease in FRDA patients and then introduces gene-targeted and pathology-specific therapies as well as screening guidelines that should be used to monitor cardiac disease in this mitochondrial disorder.

A 49-year-old female with congenitally corrected (or levo-) transposition of the great arteries complicated by nonischemic cardiomyopathy presented for worsening heart failure despite guideline-directed medical therapy and was found to be in cardiogenic shock. She successfully underwent ventricular assist device placement with a HeartMate III to her systemic right ventricle as a bridge to transplantation.

BACKGROUND: The ventricular tachycardia (VT) circuit is often assumed to be located in the endocardium or epicardium. The plateauing success rate of VT ablation warrants reevaluation of this mapping paradigm. OBJECTIVE: The purpose of this study was to resolve the intramural components of VT circuits by mapping in human hearts. METHODS: Panoramic simultaneous endocardial-epicardial mapping (SEEM) during intraoperative mapping (IOM) was performed in human subjects. In explanted hearts (EH), SEEM and intramural multielectrode plunge needle mapping (NM) of the left ventricle were performed. Overall, 37 VTs (26 ischemic cardiomyopathy [ICM], 11 nonischemic cardiomyopathy [NICM]) were studied in 32 patients. Intraoperative SEEM was performed in 16 patients (16 ICM). Additionally, 16 explanted myopathic human hearts (9 NICM, 7 ICM) were studied in a Langendorff setup. Predominant intramural location of the VT was imputed by the absence of significant endocardial-epicardial activation during IOM (using SEEM and no NM) or by the presence of intramural activation spanning the entire cycle length (including mid-diastole) in EH (SEEM and NM). RESULTS: By IOM (SEEM), predominant endocardial activation (entire tachycardia cycle length including mid-diastolic activation) was present in 10 of 18 VTs (55%). In 8 of 18 VTs (44%), the VT circuit was presumed to be intramural due to incomplete diastolic activation in endocardium and epicardium. In EH (SEEM and NM), VT location was predominantly intramural, endocardial, and epicardial in 8 of 19 (42%), 5 of 19 (26%), and 1 of 19 VTs (5%), respectively. CONCLUSION: In a significant proportion of both ischemic and nonischemic ventricular tachycardias, the predominant activation was located in the intramural space. This work was funded by CIHR MOP: 142272. Dr Bhaskaran is a Burnett fellow. Dr Nanthakumar is an investigator at TGHRI and HSF. Sí

Background The mechanisms for scar-related ventricular tachycardia (VT) originating from the periaortic region remain incompletely characterized. Objective The purpose of this study was to map the circuits responsible for periaortic VT in high resolution. Methods Cases with periaortic VT (2016–2020) were analyzed to characterize the substrate and mechanisms with multielectrode mapping. Periaortic VT was defined as low-voltage and/or deceleration zones within 2 cm of the left ventriculoaortic junction with a corresponding critical site during VT. Results Forty-nine periaortic monomorphic VTs were analyzed in 30 patients (25% of all patients with nonischemic cardiomyopathy). Isolated periaortic substrate was observed in 27% of patients, with 73% having concomitant scar, most commonly in the mid-septum (47%). Deceleration zones were equally prevalent on the septal and lateral portions of the periaortic region (87% vs 73%; P = .19). During activation mapping of VT (tachycardia cycle length 392 ± 105 ms), localized reentrant patterns of activation (14 mm [10–17 mm] × 10 mm [7–14 mm]) were demonstrated in 63% and 37% of VTs showed centrifugal activation, consistent with a focal breakout pattern. Ninety-three percent of VTs fulfilled criteria for a reentrant mechanism. Sixty-five percent of reentrant circuits had endocardial activation gaps within the tachycardia cycle length (3-dimensional circuitry), which were associated with higher rates of recurrence as compared with 2-dimensional complete circuits at 1 year (73% vs 37%; P = .028). Conclusion Periaortic VTs were observed in 25% of patients with nonischemic cardiomyopathy and scar-related VT. For the first time, localized reentry confined to this anatomically challenging region was demonstrated as the predominant mechanism by high-resolution circuit activation mapping.

Cardiovascular magnetic resonance is a versatile tool that enables noninvasive characterization of cardiac tissue structure and function. Parametric mapping techniques have allowed unparalleled differentiation of pathophysiological differences in the myocardium such as the delineation of myocardial fibrosis, hemorrhage, and edema. These methods are increasingly used as part of a tool kit to characterize disease states such as cardiomyopathies and coronary artery disease more accurately. Currently conventional mapping techniques require separate acquisitions for T1 and T2 mapping, the values of which may depend on specifics of the magnetic resonance imaging system hardware, pulse sequence implementation, and physiological variables including blood pressure and heart rate. The cardiac magnetic resonance fingerprinting (cMRF) technique has recently been introduced for simultaneous and reproducible measurement of T1 and T2 maps in a single scan. The potential for this technique to provide consistent tissue property values independent of variables including scanner, pulse sequence, and physiology could allow an unbiased framework for the assessment of intrinsic properties of cardiac tissue including structure, perfusion, and parameters such as extracellular volume without the administration of exogenous contrast agents. This review seeks to introduce the basics of the cMRF technique, including pulse sequence design, dictionary generation, and pattern matching. The potential applications of cMRF in assessing diseases such as nonischemic cardiomyopathy are also briefly discussed, and ongoing areas of research are described.

BACKGROUND: Cardiac resynchronization therapy (CRT) induces segmental left ventricular (LV) remodeling. LV lead position (LV-LP) impacts response to CRT and remodeling.OBJECTIVE: We aimed to assess segmental remodeling concordant, adjacent, and remote to LV-LP using cardiac computed tomography (CT).METHODS: We included patients from the ImagingCRT (Empiric versus Imaging-Guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy) Trial. A dynamic cardiac CT was performed at baseline and after 6 months. We assessed systolic wall thickening (WT) and exact LV-LP from the CT scans according to a 16 segmental model. Response to CRT was defined as ≥15% reduction in LV end-systolic volume.RESULTS: A total of 107 consecutive patients were included. The change in WT from baseline to follow-up was -19 % (95% CI -25 to -13, pCONCLUSION: During CRT, the systolic WT increases in segments remote to LV-LP, decreases in segments concordant, and remains unchanged in adjacent segments. Only marginal changes occur in wall thickness. In non-responders with non-ischemic cardiomyopathy, deleterious changes in segmental myocardial function occur, and further studies on how to treat these patients best are warranted.

Nonischemic cardiomyopathy (NICM) is a group of noncoronary heterogonous myocardial diseases. The heterogonous nature of NICM has impeded its diagnosis. In the present case series, we demonstrate the added value of using contrast echocardiography in the characterization of NICM. Two patients of advanced age were admitted for possible acute coronary syndrome, which was subsequently excluded by coronary angiography. Conventional and contrast echocardiography revealed characteristic structural and dynamic features of the left ventricle that were compatible with two distinct NICM diseases: stress-induced cardiomyopathy and noncompaction of the ventricular myocardium. Contrast echocardiography characterizes the cardiac structure and allows for real-time assessment of myocardial motion and perfusion. It may help to distinguish diseases with different etiologies.

Catheter ablation is being increasingly performed as adjunctive treatment to prevent recurrent implantable cardioverter-defibrillator therapies in patients with nonischemic cardiomyopathy and ventricular tachycardia (VT). In the context of VT ablation, nonischemic cardiomyopathy usually refers to dilated cardiomyopathy (DCM) as one morphological phenotype. Over the past decades, progress has been made to better characterize distinct subtypes and to differentiate between causes of DCM, which has important practical and prognostic implications. The goal of this review is to summarize available data on VT ablation in patients with DCM and, more specifically, review procedural and outcome data in specific etiologies and substrate location. It will focus on our current understanding of nonischemic scars, as well as the value of multimodal imaging, image integration, and electroanatomic mapping for substrate identification, procedural planning, and ablation. In addition, recent findings from whole human heart histology of patients with DCM and VT and their potential implications for imaging and mapping will be discussed.

This study sought to characterize septal substrate in patients with nonischemic left ventricular cardiomyopathy (NILVCM) undergoing ventricular tachycardia (VT) ablation.The interventricular septum is an important site of VT substrate in NILVCM.The authors studied 95 patients with NILVCM and VT. Electroanatomic mapping using standard bipolar (1.5 mV) and unipolar (8.3 mV) low-voltage criteria identified septal scar location and size. Analysis of unipolar voltage was performed and scars quantified using graded unipolar cutoffs from 4 to 8.3 mV were correlated with delayed gadolinium-enhanced cardiac magnetic resonance (DE-CMR), performed in 57 patients.Detailed LV endocardial mapping (mean 262 ± 138 points) showed septal bipolar and unipolar voltage abnormalities (VAs) in 44 (46%) and 79 (83%) patients, most commonly with basal anteroseptal involvement. Of the 59 patients in whom the septum was targeted, bipolar and unipolar septal VAs were seen in 36 (61%) and 54 (92%). Of the 35 with CMR-defined septal scar, bipolar and unipolar septal VAs were seen in 18 (51%) and 31 (89%). In 12 patients without CMR septal scar, 6 (50%) had isolated unipolar septal VAs on electroanatomic mapping, a subset of whom the septum was targeted for ablation (44%). In the graded unipolar analysis, the optimal cutoff associated with magnetic resonance imaging septal scar was 4.8 mV (sensitivity 75%, specificity 70%; area under the curve: 0.75; 95% confidence interval: 0.60 to 0.90).Septal substrate by unipolar or bipolar voltage mapping in patients with NILVCM and VT is common. A unipolar voltage cutoff of 4.8 mV provides the best correlation with DE-CMR. A subset of patients with septal VT had normal DE-CMR or endocardial bipolar voltage with abnormal unipolar voltage.

Background: Cardiosphere-derived cells (CDCs) have yielded promising efficacy signals in early-phase clinical trials of ischemic and nonischemic cardiomyopathy. The potential efficacy of CDCs in acute myocarditis, an inflammatory cardiomyopathy without effective therapy, remains unexplored. Given that CDCs produce regenerative, cardioprotective, anti-inflammatory, and anti-fibrotic effects (all of which could be beneficial in acute myocarditis), we investigated the efficacy of intracoronary delivery of CDCs in a rat model of experimental autoimmune myocarditis. Methods: Lewis rats underwent induction of experimental autoimmune myocarditis by subcutaneous footpad injection of purified porcine cardiac myosin supplemented with Mycobacterium tuberculosis on days 1 and 7. On day 10, rats were randomly assigned to receive global intracoronary delivery of 500 000 CDCs or vehicle. Global intracoronary delivery was performed by injection of cells or vehicle into the left ventricular (LV) cavity during transient occlusion of the aortic root. Rats were euthanized 18 days after infusion. Cardiac volumes and systolic function were assessed by serial echocardiography, performed on days 1, 10, and 28. Myocardial inflammation, T-cell infiltration, and cardiac fibrosis were evaluated by histology. Results: Experimental autoimmune myocarditis was successfully induced in 14/14 rats that completed follow-up. Left ventricular ejection fraction (LVEF) and volumes were comparable on days 1 and 10 between groups. CDC infusion resulted in increased LVEF (81.5% ± 3% vs 65.4% ± 8%, P < .001) and decreased LV end-systolic volume (43 ± 15 vs 100 ± 24 μL, P < .001) compared to placebo administration at 18 days post-infusion. Cardiosphere-derived cell infusion decreased myocardial inflammation (7.4% ± 7% vs 20.7% ± 4% of myocardium, P = .007), cardiac fibrosis (16.6% ± 13% vs 38.1% ± 3% of myocardium, P = .008), and myocardial T-cell infiltration (30.4 ± 29 vs 125.8 ± 49 cells per field, P = .005) at 18 days post-infusion compared to placebo administration. Conclusion: Intracoronary delivery of CDCs attenuates myocardial inflammation, T-cell infiltration, and fibrosis while preventing myocarditis-induced systolic dysfunction and adverse remodeling in rats with experimental autoimmune myocarditis.

Key Clinical Message A patient with permanent atrial fibrillation, triple mechanical prosthetic valve replacements, and nonischemic cardiomyopathy presented with symptomatic high‐grade atrioventricular block. A transvenous implantable cardioverter‐defibrillator system was achieved with the defibrillator lead and bipolar pace‐sense lead in separate anterolateral branches of the coronary sinus with successful defibrillation testing.

Key Clinical Message This report shows a postmortem examination of a heart performed in a patient with cardiac sarcoidosis undergoing a sequential and simultaneous unipolar radiofrequency ablation. A combination of a sequential and simultaneous unipolar radiofrequency ablation might be useful for creating transmural ablation lesions on the interventricular septum in patients with cardiac sarcoidosis.

BACKGROUND: Although cardiac MR and T1 mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T1 values in healthy and diseased myocardium, particular in nonischemic cardiomyopathies (NICM) and populations with increased cardiovascular risk, seem contradictory.PURPOSE: To determine the range of native myocardial T1 value ranges in patients with NICM and populations with increased cardiovascular risk.STUDY TYPE: Systemic review and meta-analysis.POPULATION: Patients with NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and patients with myocarditis (MC), iron overload, amyloidosis, Fabry disease, and populations with hypertension (HT), diabetes mellitus (DM), and obesity. FIELD STRENGTH/SEQUENCE: (Shortened) modified Look-Locker inversion-recovery MR sequence at 1.5 or 3T.ASSESSMENT: PubMed and Embase were searched following the PRISMA guidelines.STATISTICAL TESTS: The summary of standard mean difference (SMD) between the diseased and a healthy control populations was generated using a random-effects model in combination with meta-regression analysis.RESULTS: The SMD for HCM, DCM, and MC patients were significantly increased (1.41, 1.48, and 1.96, respectively, P < 0.01) compared with healthy controls. The SMD for HT patients with and without left-ventricle hypertrophy (LVH) together was significantly increased (0.19, P = 0.04), while for HT patients without LVH the SMD was zero (0.03, P = 0.52). The number of studies on amyloidosis, iron overload, Fabry disease, and HT patients with LVH did not meet the requirement to perform a meta-analysis. However, most studies reported a significantly increased T1 for amyloidosis and HT patients with LVH and a significant decreased T1 for iron overload and Fabry disease patients.DATA CONCLUSIONS: Native T1 mapping by using an (Sh)MOLLI sequence can potentially assess myocardial changes in HCM, DCM, MC, iron overload, amyloidosis, and Fabry disease compared to controls. In addition, it can help to diagnose left-ventricular remodeling in HT patients.LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.