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A 49-year-old man with dilated cardiomyopathy (left ventricular ejection fraction 50%, unremarkable left ventricular biopsy) developed atrioventricular conduction abnormalities (AV block II type Wenckebach) during exercise testing.

Objectives The goal of this study was to characterize the relationship between DF, the electroanatomic mapping (EAM) substrate, and outcomes of catheter ablation of VT in NICM. Background A substantial proportion of patients with nonischemic dilated cardiomyopathy (NICM) and ventricular tachycardia (VT) do not have scar detectable by cardiac magnetic resonance late gadolinium enhancement (LGE) imaging. In these patients, the significance of diffuse fibrosis (DF) detected with T1 mapping has not been previously investigated. Methods This study included 51 patients with NICM and VT undergoing catheter ablation (median age 55 years; 77% male subjects) who had no evidence of LGE on pre-procedural cardiac magnetic resonance. Post-contrast T1 relaxation time determined on the septum was assessed as a surrogate of DF burden. The extent of endocardial low-voltage areas (LVAs) at EAM was correlated with T1 mapping data. Results Bipolar LVAs were present in 22 (43%) patients (median extent 15 cm2 [8 to 29 cm2]) and unipolar LVA in all patients (median extent 48 cm2 [26 to 120 cm2]). A significant inverse correlation was found between T1 values and both unipolar-LVA (R2 = 0.64; β = –0.85; p Conclusions In patients with NICM and no evidence of LGE undergoing catheter ablation of VT, DF estimated by using post-contrast T1 mapping correlates with the voltage abnormality at EAM and seems to affect post-ablation outcomes.

The indications for mitral valve surgery in patients with advanced nonischemic dilated cardiomyopathy and functional mitral regurgitation are still unclear. We reviewed our experience of mitral valve surgery in such patients and explored factors that were predictive of outcomes. Fifty-three consecutive patients with nonischemic dilated cardiomyopathy and an ejection fraction35% who underwent mitral valve surgery were reviewed. Thirty five patients (66%) suffered all-cause death or underwent admission for heart failure or left ventricular assist device implantation after mitral valve surgery during follow-up (37 ± 27 months); freedom from these events at 3 years was 45%. Mitral valve surgery significantly reduced left ventricular volume (P0.01) and pulmonary vascular resistance (P0.01) in survivors. New York Heart Association functional class also improved significantly (P0.01) at 1 year after surgery. By multivariate analysis, preoperative left ventricular stroke work index (P0.04) was the sole significant predictor of composite outcomes including all-cause mortality, admission for heart failure or left ventricular assist device implantation after mitral valve surgery, with a cut-off value of 25.9 g-m/m

Truncating variants in TTN (TTNtvs) are the most common known cause of nonischemic dilated cardiomyopathy (DCM), but how TTNtvs cause disease has remained controversial. Efforts to detect truncated titin proteins in affected human DCM hearts have failed, suggesting that disease is caused by haploinsufficiency, but reduced amounts of titin protein have not yet been demonstrated. Here, we leveraged a collection of 184 explanted posttransplant DCM hearts to show, using specialized electrophoretic gels, Western blotting, allelic phasing, and unbiased proteomics, that truncated titin proteins can quantitatively be detected in human DCM hearts. The sizes of truncated proteins corresponded to that predicted by their respective TTNtvs; the truncated proteins were encoded by the TTNtv-bearing allele; and no degradation fragments from protein encoded by either allele were detectable. In parallel, full-length titin was less abundant in TTNtv(+) than in TTNtv(−) DCM hearts. Disease severity or need for transplantation did not correlate with TTNtv location. Transcriptomic profiling revealed few differences in splicing or allelic imbalance of the TTN transcript between TTNtv(+) and TTNtv(−) DCM hearts. Studies with isolated human adult cardiomyocytes revealed no defects in contractility in cells from TTNtv(+) compared to TTNtv(−) DCM hearts. Together, these data demonstrate the presence of truncated titin protein in human TTNtv(+) DCM, show reduced amounts of full-length titin protein in TTNtv(+) DCM hearts, and support combined dominant-negative and haploinsufficiency contributions to disease.

Introduction: Among the causes of de novo diagnosed cardiomyopathy, Takotsubo cardiomyopathy (TTC) plays a minor role, with an occurrence of 50,000–100,000 cases per annum in the United States. In clinical practice, a differentiation of a TTC toward an ischemic cardiomyopathy (ICMP) or a dilatative cardiomyopathy (DCMP) appears to be challenging, especially in a subacute setting or in atypical types of TTC.Methods: To investigate this issue, we analyzed serum levels of sST2, GDF-15, suPAR, HFABP, and clinical parameters including echocardiography in 51 patients with TTC, 52 patients with ischemic cardiomyopathy (ICMP) and 65 patients with dilated cardiomyopathy (DCMP).Results: sST-2 seemed to be the most promising biomarker for prediction of a TTC in differential diagnosis to an ICMP (AUC: 0.879, p = < 0.001, Cut off values: 12,140.5 pg/ml) or to a DCMP (AUC: 0.881, p = < 0.001, cut off value: 14521.9 pg/ml). GDF-15 evidenced a slightly lower AUC for prediction of a TTC in differential diagnosis to an ICMP (AUC: 0.626, p = 0.028) and to a DCMP (AUC: 0.653, p = 0.007). A differential diagnostic value was found for H-FABP in the prediction of a DCMP compared to TTC patients (AUC: 0.686, p = < 0.001). In propensity score matching for left ventricular ejection fraction, sex, and cardiovascular risk factors, differences in the plasma levels of sST2 and H-FABP in the matched cohort of TTC vs. DCMP remained statistically significant. In the matched cohort of TTC vs. ICMP, differences in sST2 also remained statistically significantConclusion: As medical therapy, long term prognosis, interval of follow-ups, rehabilitation program and recommendations differ completely between TTC and ICMP/DCMP, biomarkers for differential diagnosis, or rather for confirmation of diagnosis, are warranted in cases of cardiomyopathies with unsure origin. sST-2, GDF-15 and H-FABP might facilitate the classification.

This study investigated the feasibility of using cardiovascular magnetic resonance feature tracking (CMR-FT) for analysis of left ventricular (LV) strain and strain rate in patients with non-ischemic dilated cardiomyopathy (NIDCM) combined with ventricular arrhythmias (VAs). And evaluated the correlation between the LV global strain and left ventricular ejection (LVEF). We performed a retrospective study in a cohort of 34 consecutive patients with NIDCM combined with VAs who underwent CMR examination in our hospital between January 2016 and December 2019. Global and segmental peak values of LV longitudinal, circumferential, radial strain, and systolic strain rate were analyzed. Pearson analysis was calculated to assess the correlation of LV global deformation and LVEF as well as the correlation of between LV global deformation. Compared with the healthy controls, the global peak radial strain (GPRS), global peak circumferential strain (GPCS), and global peak longitudinal strain (GPLS) were significantly reduced in patients with NIDCM combined with VAs (P

Background Clinical effectiveness of autologous skeletal cell‐patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This clinical study aimed to determine the feasibility, safety, therapeutic efficacy, and the predictor of responders of this treatment in patients with nonischemic dilated cardiomyopathy. Methods and Results Twenty‐four nonischemic dilated cardiomyopathy patients with left ventricular ejection fraction P P 2 ·beat [22.7–35.5 g·m 2 ·beat] to 32.8 g·m 2 ·beat [28–38.5 g·m 2 ·beat], P =0.21). However, such improvement was not observed in the nonresponders. In responders, the actuarial survival rate was 90.9±8.7% at 5 years, which was superior to the estimated survival rate of 70.9±5.4% using the Seattle Heart Failure Model. However, they were similar in nonresponders (47.7±21.6% and 56.3±8.1%, respectively). Multivariate regression model with B‐type natriuretic peptide, pulmonary capillary wedge pressure, and expression of histone H3K4me3 (H3 lysine 4 trimethylation) strongly predicted the responder of this treatment (B‐type natriuretic peptide: odds ratio [OR], 0.96; pulmonary capillary wedge pressure: ​OR, 0.58; H3K4me3: OR, 1.35, receiver operating characteristic–area under the curve, 0.96, P Conclusions This clinical trial demonstrated that autologous skeletal stem cell–patch implantation might promise functional recovery and good clinical outcome in selected patients with nonischemic dilated cardiomyopathy, in addition to safety and feasibility. Registration URL: http://www.umin.ac.jp/english/ . Unique identifiers: UMIN000003273, UMIN0000012906 and UMIN000015892.

A 50-year-old male with a history of nonischemic dilated cardiomyopathy presented in cardiogenic shock and ultimately underwent durable left ventricular assist device implantation. He recovered well initially but developed persistent bacteremia. His indwelling pacemaker leads were extracted due to evidence of vegetation. Shortly thereafter, around 3 months post–left ventricular assist device, he succumbed to a massive intracranial hemorrhage due to ruptured cerebral mycotic aneurysm. This case highlights the potential importance of brain imaging in left ventricular assist device patients with persistent bacteremia to avoid this likely catastrophic complication.

Objectives: In patients with nonischemic dilated cardiomyopathy (NIDCM), native T1, partition coefficient (λGd), and extracellular volume fraction (ECV) mapping may offer prognostic values ...

BACKGROUND The benefits of implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac arrest (SCA) are well established. However, a significant knowledge gap remains regarding current indications and utilization of ICDs in real-world settings in Asia. METHODS Patients who underwent ICD implantation in South Korea from 2007 to 2015 were identified using the Health Insurance Review and Assessment Service database. We investigated trends in use of ICD for the prevention of SCA. RESULTS A total of 4649 ICDs were implanted during 9 years. ICDs were implanted in 1448 (31.2%) patients for primary prevention and in 3201 (68.8%) for secondary prevention. The proportion of ICDs for primary prevention increased from 6.1% in 2007 to 41.9% in 2015. Primary prevention was more frequent in older (≥40 years) recipients (34.4% vs. 14.6%, P

Due to an unfortunate turn of events, part of the data in the columns HR, 95% CI and p is missing from Figs. 4–9 of the original publication.

BACKGROUND The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR) RESULTS After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.092.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction #35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene. (J Am Coll Cardiol 2021;78:1682-1699) (c) 2021 by the American College of Cardiology Foundation.

Risk stratification for ventricular arrhythmias (VA) and sudden death in nonischemic dilated cardiomyopathy (DCM) remains suboptimal.The goal of this study was to provide an improved risk stratification algorithm for VA and sudden death in DCM.This was a retrospective cohort study of consecutive patients with DCM who underwent cardiac magnetic resonance with late gadolinium enhancement (LGE) at 2 tertiary referral centers. The combined arrhythmic endpoint included appropriate implantable cardioverter-defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, and sudden death.In 1,165 patients with a median follow-up of 36 months, LGE was an independent and strong predictor of the arrhythmic endpoint (hazard ratio: 9.7; p 0.001). This association was consistent across all strata of left ventricular ejection fraction (LVEF). Epicardial LGE, transmural LGE, and combined septal and free-wall LGE were all associated with heightened risk. A simple algorithm combining LGE and 3 LVEF strata (i.e., ≤20%, 21% to 35%,35%) was significantly superior to LVEF with the 35% cutoff (Harrell's C statistic: 0.8 vs. 0.69; area under the curve: 0.82 vs. 0.7; p 0.001) and reclassified the arrhythmic risk of 34% of patients with DCM. LGE-negative patients with LVEF 21% to 35% had low risk (annual event rate 0.7%), whereas those with high-risk LGE distributions and LVEF35% had significantly higher risk (annual event rate 3%; p = 0.007).In a large cohort of patients with DCM, LGE was found to be a significant, consistent, and strong predictor of VA or sudden death. Specific high-risk LGE distributions were identified. A new clinical algorithm integrating LGE and LVEF significantly improved the risk stratification for VA and sudden death, with relevant implications for implantable cardioverter-defibrillator allocation.

The human mutant cardiac α-actins p.A295S or p.R312H (plus p.R312K) and p.E361G correlated with hypertrophic or dilative cardiomyopathy, respectively, were expressed by using the baculovirus/Sf21 insect cell system. After purification their biochemical and cell biological properties were analysed and compared to wild type (wt) cardiac actin identically obtained or conventionally isolated from bovine hearts. DNase I inhibition and their polymerization behaviour indicated that all c-α-actins had maintained their native state. Cardiomyopathy type specific differences were observed except for the p.R312K mutant, which behaved like wt c-α-actin. The extent of myosin-S1 ATPase stimulation by the c-actin variants and its Ca2+-sensitivity after decoration with tropomyosin (cTm) and troponin complex (cTn) varied being highest for the HCM p.A295S and lower for both DCM mutants. Similar Ca2+-sensitivity differences were observed by recording the fluorescence increase of pyrene-cTm in the absence or presence of myosin-S1 and/or the actin-binding N-terminal fragment of cardiac myosin binding protein C (N-cMyBP-C). Transfection experiments showed the incorporation of the c-actin variants into existing cytoskeletal elements of non-muscle cells. Wt and p.A295S c-α-actin preferably incorporated into the microfilament system and p.R312H and p.E361G into the submembranous actin network of MDCK cells. Transduction of neonatal rat cardiomyocytes with adenoviral constructs coding for HA-tagged c-α-actins showed their incorporation into thin filaments of nascent sarcomeric structures at their plus ends (Z-lines) except the p.E361G mutant, which preferably incorporated at the minus ends. Our data indicate functional differences of the c-α-actins that may be causative for the different cardiomyopathy phenotypes.

Background Patients with ischemic (IHD) and nonischemic (NICM) dilated heart disease and reduced left ventricular ejection fraction are at increased risk of ventricular tachycardias (VTs) or sudden cardiac death. VT catheter ablation is an invasive treatment modality for antiarrhythmic drugs-resistant VT that reduces arrhythmic episodes, improves quality of life and improves survival in patients with electrical storm. Direct comparison of the outcomes from combined and non-combined endoepicardial ablations is limited by patient characteristics, follow-up durations, protocols heterogeneity and scarcity of randomized trials. We aim to investigate the long-term clinical outcomes of these 2 strategies in the IHD and NICM populations. Methods Multicentric observational registry including 316 consecutive patients who underwent combined (C-ABL) and non-combined (NC-ABL) endoepicardial ventricular tachycardia (VT) ablation for drug-resistant VT between January 2008 and July 2019. Chagas' disease patients were excluded. Primary and secondary efficacy endpoints were defined as VT-free survival and all-cause death after ablation. Safety outcomes were defined by 30-days mortality and procedure-related complications. Results Most of the patients were male (85%), with IHD (67%) and a mean age of 63±13 years. During a mean follow-up of 3±2 years, 117 (37%) patients had VT recurrence and 73 (23%) died. Multivariate survival analysis identified storm (ES) at presentation (HR=2.17; 95% CI 1.44–3.25), IHD (HR=0.53, 95% CI 0.36–0.78), left ventricular ejection fraction (LEVF) (HR=0.97, 95% CI 0.95–0.99), New York Heart Association (NYHA) functional class III or IV (HR=1.79, 95% CI 1.13–2.85) and C-ABL (HR=0.49, 95% CI 0.27–0.92) as independent predictors of VT recurrence. In 135 patients undergoing two or more ablation procedures only C-ABL (HR=0.36, 95% CI 0.17–0.80) and ES at presentation (HR=2.42, 95% CI 1.24–4.70) were independent predictors of arrhythmia recurrence. The independent predictors of all-cause mortality were ES (HR=2.17, 95% CI 1.33–3.54), LVEF (HR=0.95, 95% CI 0.92–0.98), age (HR=1.03, 95% CI 1.01–1.05), NYHA functional class III or IV (HR=2.04, 95% CI 1.12–3.73), and C-ABL (HR=0.22, 95% CI 0.05–0.91). The survival benefit was only seen in patients with a previous ablation (P for interaction=0.04) – Figure 1. Mortality at 30-days was similar between NC-ABL and C-ABL (4% vs. 2%, respectively, P=0.777), as was the complication rate (10.3% vs. 15.1% respectively, P=0.336). Conclusion A combined endo-epicardial approach appears to be associated with greater VT-free survival and overall survival in ischemic and nonischemic patients undergoing repeated VT catheter ablations. Both strategies seem equally safe. Survival analysis for C-ABL vs NC-ABL Funding Acknowledgement Type of funding source: None

ObjectivesThis 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).BackgroundThe 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.MethodsCardiac 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.ResultsDuring 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 ConclusionsThe area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

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.

The causes of nonischemic dilated cardiomyopathy are classified as genetic or nongenetic, but environmental factors such as metal pollutants may interact with genetic susceptibility. The presence of metal particles has been detected in the myocardium, including in those patients with dilated cardiomyopathy. It is also known that hypersensitivity reactions can induce inflammation in tissue. The present study aimed to verify if metal-induced delayed-type hypersensitivity is present in patients with nonischemic dilated cardiomyopathy. The patient group consisted of 30 patients with newly diagnosed dilated cardiomyopathy; the control group comprised 41 healthy subjects. All patients and control subjects provided blood samples for lymphocyte transformation testing (MELISA®) to assess possible hypersensitivity to seven common metals. Specific exposure to metals was based on interview data. Results showed that exposure to cadmium and lead (p = 0.0002), aluminum (p = 0.0006), nickel (p = 0.0012), and chromium (p = 0.0065) was more often reported by patients than controls. The patients also had significantly more frequent hypersensitivity reactions to mercury (26.7% vs. 7.3%, p = 0.014624), nickel (40% vs. 12.2%, p = 0.02341), and silver (20% vs. 4.8%, p = 0.025468) than the control group. Patients with dilated cardiomyopathy had greater exposure to certain metals compared with healthy controls. Hypersensitivity to metals was more frequent in patients with dilated cardiomyopathy, suggesting a possible association that warrants further investigation.

To investigate the relationship between left ventricular (LV) long-axis strain (LAS) and LV sphericity index (LVSI) and outcomes in patients with nonischemic dilated cardiomyopathy (NIDCM) and myocardial replacement fibrosis confirmed by late gadolinium enhancement (LGE) using cardiac magnetic resonance imaging (cMRI), we conducted a prospective study on 178 patients (48 &plusmn, 14.4 years, 25.2% women) with first NIDCM diagnosis. The evaluation protocol included ECG monitoring, echocardiography and cMRI. LAS and LVSI were cMRI-determined. Major adverse cardiovascular events (MACEs) were defined as a composite outcome including heart failure (HF), ventricular arrhythmias (VAs) and sudden cardiac death (SCD). After a median follow-up of 17 months, patients with LGE+ had increased risk of MACEs. Kaplan-Meier curves showed significantly higher rate of MACEs in patients with LGE+ (p &lt, 0.001), increased LVSI (p &lt, 0.01) and decreased LAS (p &lt, 0.001). In Cox analysis, LAS (HR = 1.32, 95%CI (1.54&ndash, 9.14), p = 0.001), LVSI [HR = 1.17, 95%CI (1.45&ndash, 7.19), p &lt, 0.01] and LGE+ (HR = 1.77, 95%CI (2.79&ndash, 12.51), p &lt, 0.0001) were independent predictors for MACEs. In a 4-point risk scoring system based on LV ejection fraction (LVEF) &lt, 30%, LGE+, LAS &gt, &minus, 7.8% and LVSI &gt, 0.48%, patients with 3 and 4 points had a significantly higher risk for MACEs. LAS and LVSI are independent predictors of MACEs and provide incremental value beyond LVEF and LGE+ in patients with NIDCM and myocardial fibrosis.

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: Septal midwall late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is a characteristic finding in nonischemic dilated cardiomyopathy (DCM) and is associated with adverse cardiac events. QRS-prolongation in DCM is also frequently present and a predictor of arrhythmic events and mortality. Since the His-Purkinje fibres are located in the interventricular septum, QRS-prolongation may directly result from septal fibrosis, visualized by LGE. Our aim was to study the correlation of the presence and extent of septal midwall LGE and QRS-duration. Methods: DCM-patients with left ventricular (LV) dysfunction (LVEF

A 55 year old female with idiopathic nonischemic dilated cardiomyopathy and complete left bundle branch was seen in the clinic for significant dyspnea on exertion. She underwent implantation of a biventricular implantable cardioverter-defibrillator with significant improvement in her symptoms of heart failure. More recently she has been having episodes of palpitations due to medication noncompliance, and usually associated with significant weight gain. An episode of tachycardia is revealed. Mechanism of the tachycardia as well as how it terminated are discussed.

Objectives This review and meta-analysis reviews the prognostic value of cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (DCM). Background Late gadolinium-enhanced (LGE) CMR is a noninvasive method to determine the underlying cause of DCM and previous studies reported the prognostic value of the presence of LGE to identify patients at risk of major adverse cardiovascular events. Methods PubMed was searched for studies describing the prognostic implication of LGE in patients with DCM for the specified endpoints cardiovascular mortality, major ventricular arrhythmic events including appropriate implantable cardioverter-defibrillator therapy, rehospitalization for heart failure, and left ventricular reverse remodeling. Results Data from 34 studies were included, with a total of 4,554 patients. Contrast enhancement was present in 44.8% of DCM patients. Patients with LGE had increased cardiovascular mortality (odds ratio [OR]: 3.40; 95% confidence interval [CI]: 2.04 to 5.67), ventricular arrhythmic events (OR: 4.52; 95% CI: 3.41 to 5.99), and rehospitalization for heart failure (OR: 2.66; 95% CI: 1.67 to 4.24) compared with those without LGE. Moreover, the absence of LGE predicted left ventricular reverse remodeling (OR: 0.15; 95% CI: 0.06 to 0.36). Conclusions The presence of LGE on CMR substantially worsens prognosis for adverse cardiovascular events in DCM patients, and the absence indicates left ventricular reverse remodeling.

Summary Ronin (THAP11), a DNA-binding protein that evolved from a primordial DNA transposon by molecular domestication, recognizes a hyperconserved promoter sequence to control developmentally and metabolically essential genes in pluripotent stem cells. However, it remains unclear whether Ronin or related THAP proteins perform similar functions in development. Here, we present evidence that Ronin functions within the nascent heart as it arises from the mesoderm and forms a four-chambered organ. We show that Ronin is vital for cardiogenesis during midgestation by controlling a set of critical genes. The activity of Ronin coincided with the recruitment of its cofactor, Hcf-1, and the elevation of H3K4me3 levels at specific target genes, suggesting the involvement of an epigenetic mechanism. On the strength of these findings, we propose that Ronin activity during cardiogenesis offers a template to understand how important gene programs are sustained across different cell types within a developing organ such as the heart., Graphical Abstract, Highlights • Ronin displays complex expression patterns during embryogenesis • Ronin is critical for heart growth • Ronin regulates genetic growth programs • Ronin binding influences H3K4me3 levels at target genes, Fujita et al. find that the transcriptional regulator Ronin (Thap11) appears to control embryonic heart development. Early heart-specific knockout of Ronin leads to growth defects in the developing heart and embryonic lethality, whereas slightly later Ronin loss results in severe dilated cardiomyopathy in the adult.

Purpose To study the relationship between diffuse myocardial fibrosis and complex ventricular arrhythmias (ComVA) in patients with nonischemic dilated cardiomyopathy (NICM). We hypothesized that NICM patients with ComVA would have a higher native myocardial T1 time, suggesting more extensive myocardial diffuse fibrosis. Materials and Methods We prospectively enrolled NICM patients with a history of ComVA (n = 50) and age-matched NICM patients without ComVA (n = 57). Imaging was performed at 1.5T with a protocol that included cine magnetic resonance imaging (MRI) for left ventricular (LV) function, late gadolinium enhancement (LGE) for focal scar, and native T1 mapping for diffuse fibrosis assessment. Results Global native T1 time was significantly higher in patients with NICM with ComVA when compared to patients with NICM without ComVA (1131 ± 42 vs. 1107 ± 45 msec, P = 0.006), and this finding remained after excluding segments with scar on LGE (1124 ± 36 vs. 1102 ± 44 msec, P = 0.006). Native T1 was similar in NICM patients with and without the presence of LGE (1121 ± 39 vs. 1117 ± 48 msec, P = 0.68) and mildly correlated with LV end-diastolic volume index (r = 0.27, P = 0.005), LV end-systolic volume index (r = 0.24, P = 0.01), and LV ejection fraction (r = –0.28, P = 0.003). Native T1 value for each 10-msec increment was an independent predictor of ComVA (odds ratio 1.14, 95% confidence interval 1.03–1.25; P = 0.008) beyond LV function and LGE. Conclusion NICM patients with ComVA have higher native T1 compared to NICM without any documented ComVA. Native myocardial T1 is independently associated with ComVA, after adjusting for LV function and LGE. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. In memoriam: The authors are grateful for Dr. Josephson's inspiring guidance and contributions to this study.

We sought to evaluate the physiological background and the effects of CD34+ cell transplantation on diastolic parameters in nonischemic dilated cardiomyopathy patients (DCM). We enrolled 38 DCM patients with NYHA class III and LVEF < 40% who underwent transendocardial CD34+ cell transplantation. Peripheral blood CD34+ cells were mobilized by G-CSF, collected via apheresis, and injected transendocardially in the areas of myocardial hibernation. Patients were followed for 1 year. At baseline, estimated filling pressures were significantly elevated (E/e′ ≥ 15) in 18 patients (Group A), and moderately elevated (E/e ′