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Aims To evaluate the baseline characteristics and the prognostic implications associated with late gadolinium enhancement limited to the right ventricular insertion points (IP-LGE) or present at both the right ventricular insertion points and the left ventricle (IP&LV-LGE) in non-ischaemic dilated cardiomyopathy (DCM). Methods and results This is a retrospective observational multicentre cohort study including 1165 consecutive patients with DCM evaluated by cardiac magnetic resonance. The primary endpoint included appropriate defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, or sudden death. The secondary outcome encompassed heart failure hospitalizations, heart transplant, left ventricular assist device implantation, and end-stage heart failure death. IP-LGE was found in 72 patients (6%), who had clinical characteristics closer to LGE− than to LGE+ patients. During follow-up (median 36 months), none of the IP-LGE patients experienced the primary endpoint. The cumulative incidence of the primary endpoint was similar between IP-LGE and LGE− patients (P = 1), while IP-LGE had significantly lower cumulative incidence when compared with LGE+ patients (P < 0.001). When compared with IP-LGE patients, the cumulative incidence of the secondary endpoint was similar in LGE− cases (P = 0.86) but tended to be higher in LGE+ patients (P = 0.06). Both clinical characteristics and outcomes were similar between IP&LV-LGE patients and the rest of LGE+ cases. Conclusions In a large cohort of DCM patients, IP-LGE was associated with similar outcome when compared with LGE− patients and with significant lower risk of ventricular arrhythmias and sudden death when compared with LGE+ cases. Patients with IP&LV-LGE had clinical characteristics and outcomes similar to the rest of LGE+ cases. [ABSTRACT FROM AUTHOR]

Abstract Aims Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non‐ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM. Methods and results We enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high‐ATX group and low‐ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6–689.5) pg/mL vs. 96.5 (40.8–191.5) pg/mL, P = 0.010] were higher in the high‐ATX group than low‐ATX group, whereas high‐sensitivity C‐reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan–Meier survival analysis revealed that the event‐free survival rate was significantly lower in the high‐ATX group than low‐ATX group (log‐rank; P = 0.007). Cox proportional hazard analysis revealed that high‐ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high‐sensitivity C‐reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048). Conclusion High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.

Abstract Aims This study aimed to develop and validate a competing risk nomogram for predicting all‐cause mortality and heart transplantation (HT) before first appropriate shock in non‐ischaemic dilated cardiomyopathy (DCM) patients receiving implantable cardioverter‐defibrillators (ICD). Methods and results A total of 218 consecutive DCM patients implanted with ICD between 2010 and 2019 at our institution were retrospectively enrolled. Cox proportional hazards model was primarily built to identify variables associated with death and HT. Then, a Fine–Gray model, accounting for the appropriate shock as a competing risk, was constructed using these selected variables along with implantation indication (primary vs. secondary). Finally, a nomogram based on the Fine–Gray model was established to predict 1‐, 3‐, and 5‐year probabilities of all‐cause mortality and HT before first appropriate shock. The area under the receiver operating characteristic (ROC) curve (AUC), Harrell's C‐index, and calibration curves were used to evaluate and internally validate the performance of this model. The decision curve analysis was applied to assess its clinical utility. The 1‐, 3‐, and 5‐year cumulative incidence of all‐cause mortality and HT without former appropriate shock were 5.3% [95% confidence interval (CI) 2.9–9.9%], 16.6% (95% CI 11–25.0%), and 25.3% (95% CI 17.2–37.1%), respectively. Five variables including implantation indication, left ventricular end‐diastolic diameter, N‐terminal pro‐brain natriuretic peptide, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and amiodarone treatment were independently associated with it (all P

Objective: Because the presence of immunocompetent cells in the myocardium is associated with the pathological stage and/or myocardial viability, we explored relationships between functional recovery after left ventricular assist device implantation and the distribution of immunocompetent cells in non-ischaemic dilated cardiomyopathy patients. Methods: We reviewed 50 consecutive dilated cardiomyopathy patients implanted with HeartMate II at our institute between April 2013 and December 2018 who were treated with optimal medical therapy during left ventricular assist device support. Patients were stratified by improvement of the left ventricular ejection fraction at 6 months after implantation: ≥ 10% increase (Gr ≥ 10%), 5–10% (Gr 5–10%), and ≤ 5% (Gr ≤ 5%). T cells and macrophages were evaluated in the apical myocardium after left ventricular assist device implantation. Results: During left ventricular assist device support, 12 patients underwent heart transplantation and 2 patients died. Four patients with Gr ≤ 5% were readmitted because of congestive heart failure, but none with Gr ≥ 10%. Macrophages and T cells in the left ventricular myocardium with Gr ≥ 10% were significantly more present compared to those in other groups. Conclusions: The distribution of immunocompetent cells in the left ventricular myocardium might predict myocardial viability of this pathology after implantation. [ABSTRACT FROM AUTHOR]

Aims: Remodelling of the left ventricular (LV) shape is one of the hallmarks of non-ischaemic dilated cardiomyopathy (DCM) and may contribute to ventricular arrhythmias and sudden cardiac death. We sought to investigate a novel three dimensional (3D) shape analysis approach to quantify LV remodelling for arrhythmia prediction in DCM.Methods and Results: We created 3D LV shape models from end-diastolic cardiac magnetic resonance images of 156 patients with DCM and late gadolinium enhancement (LGE). Using the shape models, principle component analysis, and Cox-Lasso regression, we derived a prognostic LV arrhythmic shape (LVAS) score which identified patients who reached a composite arrhythmic endpoint of sudden cardiac death, aborted sudden cardiac death, and sustained ventricular tachycardia. We also extracted geometrical metrics to look for potential prognostic markers. During a follow-up period of up to 16 years (median 7.7, interquartile range: 3.9), 25 patients met the arrhythmic endpoint. The optimally prognostic LV shape for predicting the time-to arrhythmic event was a paraboloidal longitudinal profile, with a relatively wide base. The corresponding LVAS was associated with arrhythmic events in univariate Cox regression (hazard ratio = 2.0 per quartile; 95% confidence interval: 1.3-2.9), in univariate Cox regression with propensity score adjustment, and in three multivariate models; with LV ejection fraction, New York Heart Association Class III/IV (Model 1), implantable cardioverter-defibrillator receipt (Model 2), and cardiac resynchronization therapy (Model 3).Conclusion: Biomarkers of LV shape remodelling in DCM can help to identify the patients at greatest risk of lethal ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Abstract Aims In non‐ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all‐cause mortality and ventricular arrhythmias (VA) was evaluated. Methods and results Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction

Aims: This study aimed to develop and validate a competing risk nomogram for predicting all‐cause mortality and heart transplantation (HT) before first appropriate shock in non‐ischaemic dilated cardiomyopathy (DCM) patients receiving implantable cardioverter‐defibrillators (ICD). Methods and results: A total of 218 consecutive DCM patients implanted with ICD between 2010 and 2019 at our institution were retrospectively enrolled. Cox proportional hazards model was primarily built to identify variables associated with death and HT. Then, a Fine–Gray model, accounting for the appropriate shock as a competing risk, was constructed using these selected variables along with implantation indication (primary vs. secondary). Finally, a nomogram based on the Fine–Gray model was established to predict 1‐, 3‐, and 5‐year probabilities of all‐cause mortality and HT before first appropriate shock. The area under the receiver operating characteristic (ROC) curve (AUC), Harrell's C‐index, and calibration curves were used to evaluate and internally validate the performance of this model. The decision curve analysis was applied to assess its clinical utility. The 1‐, 3‐, and 5‐year cumulative incidence of all‐cause mortality and HT without former appropriate shock were 5.3% [95% confidence interval (CI) 2.9–9.9%], 16.6% (95% CI 11–25.0%), and 25.3% (95% CI 17.2–37.1%), respectively. Five variables including implantation indication, left ventricular end‐diastolic diameter, N‐terminal pro‐brain natriuretic peptide, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and amiodarone treatment were independently associated with it (all P < 0.05) and were used for constructing the nomogram. The 1‐, 3‐, and 5‐year AUC of the nomogram were 0.83 (95% CI 0.73–0.94, P < 0.001), 0.84 (95% CI 0.75–0.93, P < 0.001), and 0.85 (95% CI 0.77–0.94, P < 0.001), respectively. The Harrell's C‐index was 0.788 (95% CI 0.697–0.877, P < 0.001; 0.762 for the optimism‐corrected C‐index), showing the good discriminative ability of the model. The calibration was acceptable (optimism‐corrected slope 0.896). Decision curve analysis identified our model was clinically useful within the entire range of potential treatment thresholds for ICD implantation. Three risk groups stratified by scores were significantly different between cumulative incidence curves (P < 0.001). The identified high‐risk group composed 17.9% of our population and did not derive long‐term benefit from ICD. Conclusions: The proposed nomogram is a simple, useful risk stratification tool for selecting potential ICD recipients in DCM patients. It might facilitate the shared decision‐making between patients and clinicians. [ABSTRACT FROM AUTHOR]

Aims: Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non‐ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM. Methods and results: We enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high‐ATX group and low‐ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6–689.5) pg/mL vs. 96.5 (40.8–191.5) pg/mL, P = 0.010] were higher in the high‐ATX group than low‐ATX group, whereas high‐sensitivity C‐reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan–Meier survival analysis revealed that the event‐free survival rate was significantly lower in the high‐ATX group than low‐ATX group (log‐rank; P = 0.007). Cox proportional hazard analysis revealed that high‐ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high‐sensitivity C‐reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048). Conclusion: High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) is a common comorbidity in non-ischaemic dilated cardiomyopathy (NIDCM) affecting conventional measures of left atrial (LA) function. We aimed to determine whether LA function analysis could identify patients at higher risk of major cardiovascular events (MACEs)., Methods and Results: A retrospective study of patients with NIDCM in AF referred to a single centre for transthoracic echocardiography (TTE) between 2015 and 2019. Peak atrial longitudinal strain (PALS) was measured along with LA emptying fraction and LA filling index (LAFI = E wave/PALS). Cox regression analysis was conducted. A total of 153 patients were included [median age 74 years, left ventricular ejection fraction (LVEF) 35%], and 57 (37.3%) had MACE after a median follow-up of 3.2 years. LAFI was the only independent TTE parameter associated with MACE after adjustment for age, diabetes, LVEF, left ventricular global longitudinal strain (LV-GLS), and LA volume index [adjusted hazard ratio (HR) = 1.02 per point increase, P = 0.024], with the best cut-off at ≥15. LAFI ≥15 predicted each of MACE components when separately analysed: MACE HR = 1.95, 95% confidence interval (CI) 1.16-3.30; cardiovascular death HR = 3.68, 95% CI 1.41-9.56, heart failure admission HR = 2.13, 95% CI 1.19-3.80, and ventricular arrhythmia HR = 4.72, 95% CI 1.52-14.67. Higher LAFI was associated with worsening LV-GLS, E / e ', systolic pulmonary artery (PA) pressure, tricuspid annular plane systolic excursion, and right ventricular to PA coupling., Conclusion: LA deformation analysis is feasible in patients with NIDCM presenting with AF. LAFI may identify patients at higher risk of MACE and correlates with higher pulmonary pressures and worse right ventricular function, suggesting an elevation of left-sided ventricular pressures in patients with higher LAFI., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients.Methods and Results: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort.Conclusion: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation. [ABSTRACT FROM AUTHOR]

Objectives: There is uncertainty over the efficacy of additional surgical ventricular reconstruction (SVR) associated with mitral valve operation for non-ischaemic dilated cardiomyopathy (DCM). This study aims to assess mid-term outcomes of these non-heart transplant surgical approaches for DCM. Methods: We reviewed retrospectively 106 patients (median age 64, 44 females) who underwent isolated mitral annular plasty (MAP; n = 34), mitral valve replacement (MVR; n = 29), and SVR associated with MAP (SVR + MAP; n = 43) for DCM, in 11 Japanese hospitals. We analysed mid-term outcomes, specifically freedom from cardiac death and cardiac event. Results: Hospital deaths occurred in 16 patients (15.1%) and cardiac deaths in 36 patients (34.0%) during the study period of 4.4 ± 3.5 years. Freedom from cardiac death at 7 years in patients undergoing MAP, MVR, and SVR + MAP were, respectively, 79.1%, 82.6%, and 29.5% (P < 0.0001). Freedom from cardiac event at 7 years in patients undergoing MAP, MVR, and SVR + MAP were, respectively, 42.8%, 59.9%, 22.6% (P = 0.0004). In the multivariable analyses, preoperative tricuspid regurgitation (TR) grade was the only risk factor for both cardiac death and event, whereas MVR for DCM emerged as a protective factor for cardiac event. Conclusions: This study could not show any benefit of additional SVR, by means of volume reduction, to MAP, because the baseline characteristics were different even after the stratification of DCM grade. MVR can be performed with favorable mid-term outcomes even in patients with advanced DCM, while patients undergoing MAP with/without SVR had more frequent MR recurrence or cardiac events. Interestingly, the right ventricular feature is a predictor of both cardiac death and events, with the TR grade being a predictor of poor mid-term outcomes. [ABSTRACT FROM AUTHOR]

Aims: In non‐ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all‐cause mortality and ventricular arrhythmias (VA) was evaluated. Methods and results: Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction < 50%) on CMR were included retrospectively. Left atrial (LA), LV, and RV volumes and function were quantified. RV systolic dysfunction was defined as RVEF<45%. The presence and pattern of late gadolinium enhancement (LGE) on CMR were assessed visually. Septal midwall LGE was defined as midmyocardial stripe‐like or patchy hyperenhancement in the septal segments, and the extent was quantified using the full width at half maximum method. Primary endpoint was a composite of all‐cause mortality and VA, including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter defibrillator therapy. Secondary endpoints were time to all‐cause mortality alone and time to VA alone. A total of 216 DCM patients were included (42% female, age 58 ± 14 years). Mean RVEF was 46 ± 12%, and RV dysfunction was present in 38%. RVEF was moderately correlated with LA dilation (LA minimal volume ρ = −0.38, P < 0.001) and strongly correlated with LA and LV dysfunction (LA emptying fraction r = 0.58, P < 0.001 and LVEF ρ = 0.52, P < 0.001). Septal midwall LGE was more often observed in patients with RV dysfunction compared with patients with preserved RV function (respectively 40% vs. 26%, P = 0.04). No correlation was found between RVEF and the extent of septal midwall LGE (ρ = −0.12, P = 0.34). During a median follow‐up of 2.2 years [IQR 1.6–2.8], 30 patients experienced the primary endpoint. RV dysfunction was significantly associated with shorter time to the composite primary endpoint (HR 3.19 [95% CI 1.49–6.84], P < 0.01) and to the secondary endpoint of VA alone (HR 6.48 [95% CI 1.83–22.98], P < 0.01). There was a trend towards increased mortality when RV dysfunction was present (HR 2.54 [95% CI 0.99–6.57], P = 0.05). Conclusions: Right ventricular dysfunction was predominantly observed in patients with DCM with advanced heart failure and pronounced myocardial remodelling, defined as increased LV and LA dilation and dysfunction and the presence of septal midwall LGE on CMR. During follow‐up, RV dysfunction was associated with shorter time to all‐cause mortality and ventricular arrhythmic events. [ABSTRACT FROM AUTHOR]

Left atrial (LA) geometry and phasic functions are frequently impaired in non-ischaemic dilated cardiomyopathy (NIDCM). Cardiac magnetic resonance (CMR) can accurately measure LA function and geometry parameters. We sought to investigate their prognostic role in patients with NIDCM. We prospectively examined 212 patients with NIDCM (49 ± 14.2-year-old; 73.5% males) and 106 healthy controls. LA volumes, phasic functions, geometry, and fibrosis were determined using CMR. A composite outcome (cardiac death, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. LA phasic functions, sphericity index (LASI) and late gadolinium enhancement (LA-LGE) were considerably impaired in the diseased group (p < 0.001) and significantly correlated with impaired LV function parameters (p < 0.0001). After multivariate analysis, LA volumes, LASI, LA total strain (LA-εt) and LA-LGE were associated with increased risk of composite outcome (p < 0.001). Kaplan–Meier analysis showed significantly higher risk of composite endpoint for LA volumes (all p < 0.01), LASI > 0.725 (p < 0.003), and LA-εt < 30% (p < 0.0001). Stepwise Cox proportional-hazards models demonstrated a considerable incremental predictive value which resulted by adding LASI to LA-εt (Chi-square = 10.2, p < 0.001), and afterwards LA-LGE (Chi-Square = 15.8; p < 0.0001). NIDCM patients with defective LA volumes, LASI, LA-LGE and LA-εt had a higher risk for an outcome. LA-εt, LASI and LA-LGE provided independent incremental predictive value for outcome.

Objective: To investigate the association of right ventricular long axis strain (RV-LAS), a parameter of longitudinal function, with outcome in patients with non-ischaemic dilated cardiomyopathy (NIDCM).Methods: In 441 patients with NIDCM, RV-LAS was analysed retrospectively by measuring the length between the epicardial border of the left ventricular apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in end-diastole and end-systole on non-contrast standard cine sequences.Results: The primary endpoint (cardiac death or heart transplantation) occurred in 41 patients, whereas 95 reached the combined endpoint (including cardiac decompensation and sustained ventricular arrhythmias) during a median follow-up of 4.2 years. Kaplan-Meier survival curves showed a poor outcome in patients with RV-LAS values below -10% (log-rank, p < 0.0001). In a risk stratification model RV-LAS improved prediction of outcome in addition to RV ejection fraction (RVEF) and presence of late gadolinium enhancement. Assessment of RV-LAS offered incremental information compared to clinical symptoms, biomarkers and RVEF. Even in the subgroup with normal RVEF (>45%, n = 213) reduced RV-LAS was still associated with poor outcome.Conclusion: Assessment of RV-LAS is an independent indicator of outcome in patients with NIDCM and offers incremental information beyond clinical and cardiac MR parameters.Key Points: • Impaired right ventricular longitudinal function (RV-LAS) is associated with poorer cardiac outcomes. • Poor outcome is associated with decreased RV-LAS even in patients with RVEF >45%. • Addition of RV-LAS to known risk factors enhances the power prognostic information. [ABSTRACT FROM AUTHOR]

Background: Certain early-phase clinical trials have suggested that bone marrow-derived stem cell transplantation might improve left ventricular function in patients with non-ischaemic dilated cardiomyopathy (NIDCM), whereas others trials have revealed no benefit from this approach. We sought to evaluate the therapeutic effects of bone marrow-derived stem cell therapy on NIDCM. Methods: We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (through February 2016) for randomised controlled clinical trials that reported on bone marrow-derived stem cell transplantation for patients with NIDCM with a follow-up period =12 months. The co-primary endpoints were changes in mortality rate and left ventricular ejection fraction (LVEF); the secondary endpoints were changes in the 6-minute-walk test (6MWT) and left ventricular chamber size. Seven trials involving bone marrow-derived stem cell therapy that included 482 patients satisfied the inclusion and exclusion criteria. Results: Subjects who received bone marrow-derived stem cell therapy exhibited a significant reduction in mortality rate (19.7% in the cell group vs. 27.1% in the control group; 95% confidence interval (CI) -0.16 to -0.00, I² =52%, p =0.04). Bone marrow-derived stem cell therapy tended to produce LVEF improvement within 6 months (1.83% increase; 95% CI -0.27 to 3.94, I2 = 74%, p = 0.09) and significantly improved LVEF after mid-term (6-12 months) follow-up (3.53% increase; 95% CI 0.76 to 6.29, I2 =88%, p = 0.01). However, this therapy produced no significant benefit in the 6MWT (p= 0.18). Finally, the transplantation of increased numbers of stem cells resulted in no observable additional benefit with respect to LVEF. Conclusions: Bone marrow-derived stem cell therapy might have improved prognoses and appeared to provide moderate benefits in cardiac systolic function at mid-term follow-up. However, this therapy produced no observed improvement in exercise tolerance. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy is a primitive heart muscle condition, characterized by structural and functional abnormalities, in the absence of a specific cause sufficient to determine the disease. It is, though, an 'umbrella' term that describes the final common pathway of different pathogenic processes and gene-environment interactions. Performing an accurate diagnostic workup and appropriate characterization of the patient has a direct impact on the patient's outcome. The physician should adapt a multiparametric approach, including a careful anamnesis and physical examination and integrating imaging data and genetic testing. Aetiological characterization should be pursued, and appropriate arrhythmic risk stratification should be performed. Evaluations should be repeated thoroughly at follow-up, as the disease is dynamical over time and individual risk might evolve. The goal is an all-around characterization of the patient, a personalized medicine approach, in order to establish a diagnosis and therapy tailored for the individual patient., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Dilated cardiomyopathy (DCM) is a primitive heart muscle disease characterized by a great heterogeneous aetiology and prognostic outcome. Dilated cardiomyopathy is an umbrella term encompassing different aetiologies that might require specific treatments. It principally affects young and male adults, with high-risk arrhythmic competitive risk. Unfortunately, the prevention of major ventricular arrhythmic events remains a clinical challenge. In the era of advanced multimodality imaging and widely available genetic testing, electrocardiogram (ECG) continues to represent a reliable diagnostic tool, for specific work up of every single patient. However, approaching DCM patients, only a cardiomyopathy-oriented reading makes the role of ECG central in the management of DCM, both for diagnosis, prognosis, and therapeutic management. In this paper, we present four ECGs of four different DCM patients, in order to guide a cardiomyopathy-oriented ECG reading, emphasizing its impact in an early, cost-effective, and personalized diagnostic and prognostic work up in this specific setting., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Dilated cardiomyopathy is a primary disease of the heart muscle, which affects relatively young patients with a low comorbidity profile. It is characterized by structural and/or functional abnormalities leading to systolic dysfunction of the left ventricle or of both ventricles, often associated with dilatation, in the absence of an ischaemic, valvular, or pressure overload cause sufficient to explain the phenotype. Although the prognosis of the disease has greatly improved over the last few decades, prognostic stratification remains a fundamental objective, especially about the prediction of potentially life-threatening arrhythmic events. An accurate diagnostic work-up and an appropriate aetiopathogenetic characterization affect the patients' outcome and represent the essential basis of an adequate prognostic stratification. It is necessary to adopt a multiparametric approach, especially when the aim is the prediction of arrhythmic risk; it includes an integration of medical history and physical examination with cardiac imaging and genetic testing, in order to obtain a personalized diagnosis and therapeutic strategies. Furthermore, the evaluation should be repeated at every clinical check-up, considering the dynamic trend of the pathology and the arrhythmic risk changes over time. This article aims to illustrate how, starting from an exhaustive aetiological and clinical-instrumental characterization, including all diagnostic methods available at present time, it is possible to obtain a tailored diagnostic evaluation and stratification of the arrhythmic risk as accurate as possible., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To evaluate the baseline characteristics and the prognostic implications associated with late gadolinium enhancement limited to the right ventricular insertion points (IP-LGE) or present at both the right ventricular insertion points and the left ventricle (IP&LV-LGE) in non-ischaemic dilated cardiomyopathy (DCM)., Methods and Results: This is a retrospective observational multicentre cohort study including 1165 consecutive patients with DCM evaluated by cardiac magnetic resonance. The primary endpoint included appropriate defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, or sudden death. The secondary outcome encompassed heart failure hospitalizations, heart transplant, left ventricular assist device implantation, and end-stage heart failure death. IP-LGE was found in 72 patients (6%), who had clinical characteristics closer to LGE- than to LGE+ patients. During follow-up (median 36 months), none of the IP-LGE patients experienced the primary endpoint. The cumulative incidence of the primary endpoint was similar between IP-LGE and LGE- patients (P = 1), while IP-LGE had significantly lower cumulative incidence when compared with LGE+ patients (P < 0.001). When compared with IP-LGE patients, the cumulative incidence of the secondary endpoint was similar in LGE- cases (P = 0.86) but tended to be higher in LGE+ patients (P = 0.06). Both clinical characteristics and outcomes were similar between IP&LV-LGE patients and the rest of LGE+ cases., Conclusions: In a large cohort of DCM patients, IP-LGE was associated with similar outcome when compared with LGE- patients and with significant lower risk of ventricular arrhythmias and sudden death when compared with LGE+ cases. Patients with IP&LV-LGE had clinical characteristics and outcomes similar to the rest of LGE+ cases., Competing Interests: Conflict of interest: P.F.B. received a fellowship salary support grant from Alliance Medical. There is no other conflict of interest for the present study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: The aim of this study was to evaluate equilibrium radionuclide angiography (ERNA) in prediction of response to cardiac resynchronization therapy (CRT) in non-ischaemic dilated cardiomyopathy (DCM) patients.Methods and Results: Thirty-two patients (23 males, 57.5 ± 12.1 years) were prospectively included. Equilibrium radionuclide angiography and clinical evaluation were performed before and 3 months after CRT implantation. Standard deviation of left ventricle mean phase angle (SD LVmPA) and difference between LV and right ventricle mPA (LV-RVmPA) expressed in degrees (°) were used to quantify left intraventricular synchrony and interventricular synchrony, respectively. Left ventricular ejection fraction (LVEF) was also evaluated. At the baseline, mean NYHA class was 3.3 ± 0.5, LVEF 22.5 ± 5.6%, mean QRS duration 150.3 ± 18.2 ms, SD LVmPA 43.5 ± 18°, and LV-RVmPA 30.4 ± 15.6°. At 3-month follow-up, 22 patients responded to CRT with improvement in NYHA class ≥1 and EF >5%. Responders had significantly larger SD LVmPA (51.2 ± 13.9 vs. 26.5 ± 14°) and LV-RVmPA (35.8 ± 13.7 vs. 18.4 ± 13°) than non-responders. Receiver-operating characteristic curve analysis demonstrated 95% sensitivity and 80% specificity at a cut-off value of 30° for SD LVmPA, and 81% sensitivity and 80% specificity at a cut-off value of 23° for LV-RVmPA in prediction of response to CRT.Conclusion: Baseline SD LVmPA and LV-RVmPA derived from ERNA are useful for prediction of response to CRT in non-ischaemic DCM patients. [ABSTRACT FROM AUTHOR]

Aims: Remodelling of the left ventricular (LV) shape is one of the hallmarks of non-ischaemic dilated cardiomyopathy (DCM) and may contribute to ventricular arrhythmias and sudden cardiac death. We sought to investigate a novel three dimensional (3D) shape analysis approach to quantify LV remodelling for arrhythmia prediction in DCM., Methods and Results: We created 3D LV shape models from end-diastolic cardiac magnetic resonance images of 156 patients with DCM and late gadolinium enhancement (LGE). Using the shape models, principle component analysis, and Cox-Lasso regression, we derived a prognostic LV arrhythmic shape (LVAS) score which identified patients who reached a composite arrhythmic endpoint of sudden cardiac death, aborted sudden cardiac death, and sustained ventricular tachycardia. We also extracted geometrical metrics to look for potential prognostic markers. During a follow-up period of up to 16 years (median 7.7, interquartile range: 3.9), 25 patients met the arrhythmic endpoint. The optimally prognostic LV shape for predicting the time-to arrhythmic event was a paraboloidal longitudinal profile, with a relatively wide base. The corresponding LVAS was associated with arrhythmic events in univariate Cox regression (hazard ratio = 2.0 per quartile; 95% confidence interval: 1.3-2.9), in univariate Cox regression with propensity score adjustment, and in three multivariate models; with LV ejection fraction, New York Heart Association Class III/IV (Model 1), implantable cardioverter-defibrillator receipt (Model 2), and cardiac resynchronization therapy (Model 3)., Conclusion: Biomarkers of LV shape remodelling in DCM can help to identify the patients at greatest risk of lethal ventricular arrhythmias., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims To define which echocardiographic parameters are related to the degree of functional mitral regurgitation (FMR) and to establish their relationship with clinical status, plasma B-type natriuretic peptide (BNP) levels, and prognosis in patients with non-ischaemic dilated cardiomyopathy (NICMP). Methods and results Ninety patients (mean age: 50 ± 14, 31% females) with NICMP and FMR were prospectively analysed by echocardiography. Global and local left ventricular remodelling parameters such as ejection fraction and sphericity index, inter-papillary muscle distance, coaptation to septal distance, and mitral annular area, as well as mitral valve deformation indices such as tenting area (TA) and tenting distance, were measured as indicators of FMR. Patients were defined as having severe FMR [effective regurgitant orifice area (EROA) ≥ 0.2 cm2, n = 41] or non-severe FMR (EROA < 0.2 cm2, n = 49) and followed for 15 ± 3 months. Multivariate regression analysis revealed that TA had the greatest ability to predict severe FMR at a cut-off level of 3.4 cm2 with 82% sensitivity and 77% specificity. Patients with higher TA values (>3.4 cm2) had statistically higher BNP levels, worse functional status, more hospitalizations, and higher death rates. The plasma BNP level (P: 0.012) and TA (P: 0.056) were predictors of all-cause mortality. New York Heart Association class (P < 0.001) and TA (P: 0.005) were predictors of combined death or hospitalization on multivariate Cox's regression analysis. Conclusion Tenting area accurately reflects the degree of FMR at a cut-off value of 3.4 cm2 and has a strong correlation with functional status, plasma BNP, mortality, and hospitalization rates. Tenting area is also an independent predictor of mortality and hospitalizations in patients with NICMP and FMR. [ABSTRACT FROM PUBLISHER]

Background The SCD-HeFT study demonstrated a benefit of primary prevention implantable cardioverter-defibrillator (ICD) implantation in patients with non-ischaemic dilated cardiomyopathy (NIDCM). However, NIDCM may improve spontaneously, even after waiting 6-9 …months on optimal medical treatment. Objective To assess the incidence of left ventricular (LV) function improvement in patients receiving primary prevention ICDs for NIDCM. Methods All patients with NIDCM receiving primary prevention ICDs (non-cardiac resynchronisation therapy) from 2005 to the present at our institutions were retrospectively studied. All patients had NIDCM confirmed by a lack of significant stenoses on coronary angiography, a lack of significant valvular abnormalities on echo, and LV dysfunction with ejection fraction (EF) <35%. All patients had to have had a diagnosis of NIDCM for at least 9 …months and be receiving optimal medical treatment for at least 3 …months before implant according to the guidelines. All patients had at least New York Heart Association (NYHA) II symptoms. Baseline and follow-up EF was documented by quantitative echo and/or multi-gated acquisition scan. Results 332 patients were identified by a database search. Patients were aged 67±11 …years, 75% of them were male, NYHA 2.3±0.7, with EF 25±13%, and LV diastolic diameter 61±10 ….mm. Time from initial NIDCM diagnosis to implant was 11±6 …months and duration of medical treatment before implant was 8±5 …months. Treatment at the time of implant included ACE inhibitors or ARBs (85%), β blockers (77%), spironolactone (53%), loop diuretic (63%) and digoxin (50%). Repeat EF assessment was available in 309/332 (93%) 8±6 …months after implant. EF improved to >35% in 37/309 (12%) patients. Patients who improved had a shorter time from diagnosis to implant (9±3 vs 13±5 …months respectively, p=0.03). No other significant predictors were identified for patients with improved EF. Conclusions In spite of following guidelines for implantation of primary prevention ICDs in patients with NIDCM, a substantial number of patients (12%) experience improvement in LV function to levels above those recommended for ICD implant. A shorter time from diagnosis to implant may predict post-implant improvement. [ABSTRACT FROM AUTHOR]

Left atrial (LA) geometry and phasic functions are frequently impaired in non-ischaemic dilated cardiomyopathy (NIDCM). Cardiac magnetic resonance (CMR) can accurately measure LA function and geometry parameters. We sought to investigate their prognostic role in patients with NIDCM. We prospectively examined 212 patients with NIDCM (49 ± 14.2-year-old; 73.5% males) and 106 healthy controls. LA volumes, phasic functions, geometry, and fibrosis were determined using CMR. A composite outcome (cardiac death, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. LA phasic functions, sphericity index (LASI) and late gadolinium enhancement (LA-LGE) were considerably impaired in the diseased group (p < 0.001) and significantly correlated with impaired LV function parameters (p < 0.0001). After multivariate analysis, LA volumes, LASI, LA total strain (LA-εt) and LA-LGE were associated with increased risk of composite outcome (p < 0.001). Kaplan–Meier analysis showed significantly higher risk of composite endpoint for LA volumes (all p < 0.01), LASI > 0.725 (p < 0.003), and LA-εt < 30% (p < 0.0001). Stepwise Cox proportional-hazards models demonstrated a considerable incremental predictive value which resulted by adding LASI to LA-εt (Chi-square = 10.2, p < 0.001), and afterwards LA-LGE (Chi-Square = 15.8; p < 0.0001). NIDCM patients with defective LA volumes, LASI, LA-LGE and LA-εt had a higher risk for an outcome. LA-εt, LASI and LA-LGE provided independent incremental predictive value for outcome. [ABSTRACT FROM AUTHOR]

To assess the incidence and clinical significance of ventricular late potentials in non-ischaemic dilated cardiomyopathy, 51 consecutive (44 male, seven female, mean age 53± 11 years) patients with dilated cardiomyopathy were studied. Twenty-eight patients (55%) were in New York Heart Association functional class III or IV, 34 out of 51 (76%) had a left ventricular ejection fraction of less than 40%, 10 out of 51 (20%) had a history of sustained ventricular tachycardia ( VT), 24 out of 37 (65%) had runs of non-sustained ventricular tachycardia during Holier monitoring and 15 out of 51 (29%) had a left bundle branch block. A signal-averaged electrocardiogram (gain 10 x, bipolar chest leads, filters 100–300 Hz) was performed in all the patients; late potentials were considered present if the total filtered QRS duration was longer than 118 ms and the interval between the end of QRS and the voltage 40 μV was more than 40 ms in the absence of left bundle branch block (total filtered QRS duration > 140 ms and interval between the end of QRS and the voltage 40 μV>50ms in the presence of left bundle branch block). Ventricular late potentials were detected in 22 out of 51 patients (43%). Late potentials were present in 80% (eight out of 10) of patients with sustained ventricular tachycardia but in only 34% (14 of 41) without sustained ventricular tachycardia (P < 0.01). This difference remained statistically significant even when patients with a left bundle branch block were excluded from the analysis (4 out of 6 vs 4 out of 30, P<0.01). To identify patients with dilated cardiomyopathy and sustained ventricular tachycardia, signal-averaging had a sensitivity of 80%, a specificity of 66%, a positive predictive value of 36% and a negative predictive value of 93%. It is concluded that, in non-ischaemic dilated cardiomyopathy, the signal-averaged electrocardiogram allows the identification of patients with sustained ventricular tachycardia, even in the presence of a left bundle branch block. [ABSTRACT FROM PUBLISHER]

Aims: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients., Methods and Results: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort., Conclusion: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Patients with scar-associated fibrotic tissue remodelling are at greater risk of ventricular arrhythmic events, but current methods to detect the presence of such remodelling require invasive procedures. We present here a potential method to detect the presence, location and dimensions of scar using pacing-dependent changes in the vectorcardiogram (VCG). Using a clinically-derived whole-torso computational model, simulations were conducted at both slow and rapid pacing for a variety of scar patterns within the myocardium, with various VCG-derived metrics being calculated, with changes in these metrics being assessed for their ability to discern the presence and size of scar. Our results indicate that differences in the dipole angle at the end of the QRS complex and differences in the QRS area and duration may be used to predict scar properties. Using machine learning techniques, we were also able to predict the location of the scar to high accuracy, using only these VCG-derived rate-dependent changes as input. Such a non-invasive predictive tool for the presence of scar represents a potentially useful clinical tool for identifying patients at arrhythmic risk., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Certain early-phase clinical trials have suggested that bone marrow-derived stem cell transplantation might improve left ventricular function in patients with non-ischaemic dilated cardiomyopathy (NIDCM), whereas others trials have revealed no benefit from this approach. We sought to evaluate the therapeutic effects of bone marrow-derived stem cell therapy on NIDCM., Methods: We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (through February 2016) for randomised controlled clinical trials that reported on bone marrow-derived stem cell transplantation for patients with NIDCM with a follow-up period ≥12 months. The co-primary endpoints were changes in mortality rate and left ventricular ejection fraction (LVEF); the secondary endpoints were changes in the 6-minute-walk test (6MWT) and left ventricular chamber size. Seven trials involving bone marrow-derived stem cell therapy that included 482 patients satisfied the inclusion and exclusion criteria., Results: Subjects who received bone marrow-derived stem cell therapy exhibited a significant reduction in mortality rate (19.7% in the cell group vs. 27.1% in the control group; 95% confidence interval (CI) -0.16 to -0.00, I 2  = 52%, p = 0.04). Bone marrow-derived stem cell therapy tended to produce LVEF improvement within 6 months (1.83% increase; 95% CI -0.27 to 3.94, I 2  = 74%, p = 0.09) and significantly improved LVEF after mid-term (6-12 months) follow-up (3.53% increase; 95% CI 0.76 to 6.29, I 2  = 88%, p = 0.01). However, this therapy produced no significant benefit in the 6MWT (p = 0.18). Finally, the transplantation of increased numbers of stem cells resulted in no observable additional benefit with respect to LVEF., Conclusions: Bone marrow-derived stem cell therapy might have improved prognoses and appeared to provide moderate benefits in cardiac systolic function at mid-term follow-up. However, this therapy produced no observed improvement in exercise tolerance.

Aims: The aim of this study was to evaluate equilibrium radionuclide angiography (ERNA) in prediction of response to cardiac resynchronization therapy (CRT) in non-ischaemic dilated cardiomyopathy (DCM) patients., Methods and Results: Thirty-two patients (23 males, 57.5 ± 12.1 years) were prospectively included. Equilibrium radionuclide angiography and clinical evaluation were performed before and 3 months after CRT implantation. Standard deviation of left ventricle mean phase angle (SD LVmPA) and difference between LV and right ventricle mPA (LV-RVmPA) expressed in degrees (°) were used to quantify left intraventricular synchrony and interventricular synchrony, respectively. Left ventricular ejection fraction (LVEF) was also evaluated. At the baseline, mean NYHA class was 3.3 ± 0.5, LVEF 22.5 ± 5.6%, mean QRS duration 150.3 ± 18.2 ms, SD LVmPA 43.5 ± 18°, and LV-RVmPA 30.4 ± 15.6°. At 3-month follow-up, 22 patients responded to CRT with improvement in NYHA class ≥1 and EF >5%. Responders had significantly larger SD LVmPA (51.2 ± 13.9 vs. 26.5 ± 14°) and LV-RVmPA (35.8 ± 13.7 vs. 18.4 ± 13°) than non-responders. Receiver-operating characteristic curve analysis demonstrated 95% sensitivity and 80% specificity at a cut-off value of 30° for SD LVmPA, and 81% sensitivity and 80% specificity at a cut-off value of 23° for LV-RVmPA in prediction of response to CRT., Conclusion: Baseline SD LVmPA and LV-RVmPA derived from ERNA are useful for prediction of response to CRT in non-ischaemic DCM patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Sudden cardiac death (SCD) remains a major public health problem worldwide, yet current methods to identify those at greatest risk are inadequate. High-risk individuals may benefit from potentially life-saving treatment, such as insertion of an implantable-cardioverter defibrillator (ICD). However, such treatments are expensive and have their own associated risks. Furthermore, most cases of SCD occur in the general adult population who may be relatively asymptomatic but yet have an underlying predisposition to SCD. Hence, there is great interest and clinical need in improving methods for risk stratification of SCD to identify those at greatest risk and implement the most appropriate treatment. This review provides an update on current risk-stratification methods for SCD in high-risk groups, in particular patients with reduced left ventricular function following acute myocardial infarction and those with non-ischaemic dilated cardiomyopathy, and highlights some novel methods that may have a role to play in future risk-stratification schemes. Approaches and challenges for SCD risk stratification among the general public are also discussed., Competing Interests: Disclosure: The author has no conflicts of interest to disclose.