Nonischemic Dilated Cardiomyopathy Research Articles

The Role of Circulating Collagen Turnover Biomarkers and Late Gadolinium Enhancement in Patients with Non-Ischemic Dilated Cardiomyopathy.

Background: Myocardial scarring is a primary pathogenetic process in nonischemic dilated cardiomyopathy (NIDCM) that is responsible for progressive cardiac remodeling and heart failure, severely impacting the survival of these patients. Although several collagen turnover biomarkers have been associated with myocardial fibrosis, their clinical utility is still limited. Late gadolinium enhancement (LGE) determined by cardiac magnetic resonance imaging (CMR) has become a feasible method to detect myocardial replacement fibrosis. We sought to evaluate the association between collagen turnover biomarkers and replacement myocardial scarring by CMR and, also, to test their ability to predict outcome in conjunction with LGE in patients with NIDCM. Method: We conducted a prospective study on 194 patients (48.7 ± 14.3 years of age; 74% male gender) with NIDCM. The inclusion criteria were similar to those for the definition of NIDCM, performed exclusively by CMR: (1) LV dilation with an LV end-diastolic volume (LVEDV) of over 97 mL/m2; (2) global LV dysfunction, expressed as a decreased LVEF of under 45%. CMR was used to determine the presence and extent of LGE. Several collagen turnover biomarkers were determined at diagnosis, comprising galectin-3 (Gal3), procollagen type I carboxy-terminal pro-peptide (PICP) and N-terminal pro-peptide of procollagen type III (PIIINP). A composite outcome (all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. Results: Gal3, PICP and PIIINP were considerably increased in those with LGE+ (p < 0.001), also being directly correlated with LGE mass (r2 = 0.42; r2 = 0.44; r2 = 0.31; all p < 0.001). Receiver operating characteristic (ROC) analysis revealed a significant ability to diagnose LGE, with an area under the ROC of 0.816 for Gal3, 0.705 for PICP, and 0.757 for PIIINP (all p < 0.0001). Kaplan–Meier analysis showed that at a threshold of >13.8 ng/dL for Gal3 and >97 ng/dL for PICP, they were able to significantly predict outcome (HR = 2.66, p < 0.001; HR = 1.93, p < 0.002). Of all patients, 17% (n = 33) reached the outcome. In multivariate analysis, after adjustment for covariates, only LGE+ and Gal3+ remained independent predictors for outcome (p = 0.008; p = 0.04). Nonetheless, collagen turnover biomarkers were closely related to HF severity, providing incremental predictive value for severely decreased LVEF of under 30% in patients with NIDCM, beyond that with LGE alone. Conclusions: In patients with NIDCM, circulating collagen turnover biomarkers such as Gal3, PICP and PIIINP are closely related to the presence and extent of LGE and can significantly predict cardiovascular outcome. The joint use of LGE with Gal3 and PICP significantly improved outcome prediction.

Incidence and Predictors of Eosinophilic Myocardial Hypersensitivity in Patients Receiving Home Dobutamine.

We sought to examine incidence and predictors of eosinophilic myocardial hypersensitivity (EMH) in a cohort of patients in the home inotrope program of a quaternary cardiac transplant center. Patients on home inotropes with progression to heart transplantation or ventricular assist device (VAD) between January 2000 and May 2020 were included. EMH was diagnosed by the presence of an interstitial predominate eosinophilic infiltrate within the myocardium by experienced cardiac pathologists. From a cohort of 74 patients, 58% (43) were on dobutamine and 42% (31) were on milrinone. Dobutamine was associated with EMH incidence of 14% (6/43), with zero cases in the milrinone cohort. Mean age was 52 ± 12 years, 22% were female. More than half (62%) were nonischemic dilated cardiomyopathies, the remainder were ischemic cardiomyopathy. Dobutamine dose [250 (200-282) vs. 225 (200-291) μg/min] and duration of therapy [41 (23-79) vs. 53 (24-91) days] was similar between those with and without EMH. Median change in eosinophil count was 0.31 × 10 9 /L in the EMH group compared with only 0.03 × 10 9 /L in the non-EMH cohort, P = 0.02. Increase in peripheral eosinophil count of >0.20 × 10 9 /L demonstrated good discrimination between those with and without EMH, c-statistic 0.83 (95% CI 0.66-1.0). Heart failure hospitalization occurred in 83% of the EMH group versus 59% in the non-EMH group, P = 0.26. Requirement for VAD was significantly higher in the EMH group (83% vs. 41%, P = 0.05). In conclusion, EMH occurred in 14% of patients receiving home dobutamine. Rising eosinophil count should prompt physicians to consider EMH and switch to milrinone to avoid possible escalation to VAD.

Impact of type 2 diabetes mellitus on left ventricular deformation in non-ischemic dilated cardiomyopathy patients assessed by cardiac magnetic resonance imaging

BackgroundType 2 diabetes mellitus (T2DM) increases the risk of worse long-term outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). However, the additive effects of T2DM on left ventricular (LV) function in NIDCM remain unclear. Accordingly, we aimed to investigate the impact of comorbid T2DM on LV deformation in NIDCM individuals.Materials and methodsThree hundred forty-two NIDCM patients without T2DM [NIDCM (T2DM−)], 93 with T2DM [NIDCM (T2DM+)] and 80 age- and sex-matched normal controls who underwent cardiac magnetic resonance scanning were included. LV geometry, function, and LV global strains, including peak strain (PS), peak systolic strain rate (PSSR) and peak diastolic strain rate (PDSR) in the radial, circumferential and longitudinal directions, were measured. NIDCM (T2DM+) patients were divided into two subgroups based on the HbA1c level (< 7.0% and ≥ 7.0%). The determinants of reduced LV myocardial strain for all NIDCM individuals and NIDCM (T2DM+) patients were assessed using multivariable linear regression analyses.ResultsCompared with normal controls, both NIDCM (T2DM −) and NIDCM (T2DM+) patients exhibited increased LV end-diastolic and end-systolic volume index and decreased LV ejection fraction. LV global strains progressively declined from the normal controls to the NIDCM (T2DM−) group to the NIDCM (T2DM+) group (all p < 0.017), except for radial PDSR and PSSR. Subgroup analysis showed that LV global radial PS and longitudinal PS, PSSR-L and PDSR-L were worse in NIDCM patients with poor glycemic control than in those with good glycemic control (p < 0.017). T2DM was an independent determinant of reduced LV global circumferential PS and longitudinal PS in patients with NIDCM (both p < 0.05). An increased HbA1c level was independently associated with a decreased global radial PS (β = − 0.285, p < 0.01) and longitudinal PS (β = 0.320, p < 0.01) in NIDCM (T2DM+) patients.ConclusionsT2DM has an additive deleterious effect on LV systolic and diastolic function in NIDCM patients. Among NIDCM patients with T2DM, HbA1c was found to be associated with reduced LV myocardial strain.

Prevalence and prognostic relevance of myocardial inflammation and cardiotropic viruses in non-ischemic dilated cardiomyopathy.

BackgroundNon-ischemic dilated cardiomyopathy (DCM) is a heterogeneous disease with a spectrum of etiological factors. However, subsets of the disease are not well-characterized with respect to these factors. The aim of this study was to evaluate the prevalence of myocardial inflammation and cardiotropic viruses in DCM patients and their impact on clinical outcome.MethodsFifty-seven patients with DCM underwent endomyocardial biopsy between 2010 and 2013. Biopsies were analyzed by polymerase chain reaction (PCR) for the presence of cardiotropic viruses, and inflammatory cell infiltration was assessed by immunohistochemistry. During a 5-year follow-up, 27 (47%) patients reached the composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death.ResultsThirty-one (54%) patients had myocardial inflammation and cardiotropic viruses were detected in 29 (52%). The most frequent viruses were parvovirus B19 and human herpesvirus type-6. Four specific sub-groups were distinguished by PCR and immunohistochemistry: virus-positive (chronic) myocarditis, autoreactive inflammatory DCM, viral DCM, non-inflammatory DCM. The presence of a viral genome in myocardium or diagnosis of inflammatory DCM did not predict the outcome of composite outcome measures (p > 0.05). However, univariate Cox regression and survival function estimation revealed an association between inflammation by a high number of T-cells and poor prognosis.ConclusionsThis study has shown that two markers — cardiotropic viruses and myocardial inflammation — are prevalent among DCM patients. They are also helpful in identifying sub-groups of DCM. An increased number of T-lymphocytes in the myocardium is a predictor of poor mid-term and long-term prognosis.

A Mild Dyssynchronous Contraction Pattern Detected by SPECT Myocardial Perfusion Imaging Predicts Super-Response to Cardiac Resynchronization Therapy.

BackgroundUsing single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) with phase analysis (PA), we aimed to identify the predictive value of a new contraction pattern in cardiac resynchronization therapy (CRT) response.MethodsLeft ventricular mechanical dyssynchrony (LVMD) was evaluated using SPECT MPI with PA in non-ischemic dilated cardiomyopathy (DCM) patients with left bundle branch block (LBBB) indicated for CRT. CRT super-response was defined as LV ejection fraction (EF) ≥50% or an absolute increase of LVEF >15%. The LV contraction was categorized as the mild dyssynchronous pattern when the phase standard deviation (PSD) ≤ 40.3° and phase histogram bandwidth (PBW) ≤ 111.9°, otherwise it was defined as severe dyssynchronous pattern which was further characterized as U-shaped, heterogeneous or homogenous pattern.ResultsThe final cohort comprised 74 patients, including 32 (43.2%) in mild dyssynchronous group, 17 (23%) in U-shaped group, 19 (25.7%) in heterogeneous group, and 6 (8.1%) in homogenous group. The mild dyssynchronous group had lower PSD and PBW than U-shaped, heterogeneous, and homogenous groups (P < 0.0001). Compared to patients with the heterogeneous pattern, the odds ratios (ORs) with 95% confidence intervals (CIs) for CRT super-response were 10.182(2.43–42.663), 12.8(2.545–64.372), and 2.667(0.327–21.773) for patients with mild dyssynchronous, U-shaped, and homogenous pattern, respectively. After multivariable adjustment, mild dyssynchronous group remained associated with increased CRT super-response (adjusted OR 5.709, 95% CI 1.152–28.293). Kaplan-Meier curves showed that mild dyssynchronous group demonstrated a better long-term prognosis.ConclusionsThe mild dyssynchronous pattern in patients with DCM is associated with an increased CRT super-response and better long-term prognosis.

Native Myocardial T1 Value in Predicting 1-Year Outcomes in Patients with Nonischemic Dilated Cardiomyopathy Experiencing Recent Heart Failure.

The evidence for the clinical implications, especially the short-term utility, of native myocardial T1 value (T1native) on cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (NIDCM) is scant. We investigated the potential of T1native to assess left ventricular (LV) myocardial characteristics and predict 1-year outcomes in patient with NIDCM experiencing recent heart failure (HF).Forty-five patients with NIDCM and HF symptoms within 3 months underwent CMR with cine, non-contrast T1 mapping, and late gadolinium enhancement (LGE). T1native per patient was defined as an averaged T1 value of 5 short-axis slices of base-to-apex LV myocardium. The appearance of LGE was visually examined. T1native correlated with the LV end-diastolic dimension normalized to height (LVEDD) (r = 0.38, P = 0.0103), ejection fraction (r = -0.39, P = 0.009), and serum N-terminal pro-brain natriuretic peptide levels (r = 0.48, P = 0.001), whereas the presence and segmental extent of LGE correlated only with LVEDD. In the 1-year follow-up cohort, the optimal cutoffs of T1native for predicting LV reverse remodeling (LVRR) and combined cardiac events (cardiac death, ventricular tachycardia/fibrillation, heart failure hospitalization) were 1366 ms and 1377 ms, respectively. In multivariate analysis, T1native < 1366 ms and T1native > 1377 ms remained significant predictors of LVRR (odds ratio, 11.3) and cardiac events (hazard ratio, 15.3), respectively, whereas the presence and segmental extent of LGE did not.T1native in patients with NIDCM experiencing recent HF may offer a promising strategy for assessing LV myocardial characteristics and predicting 1-year LVRR and cardiac events.

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non‐ischaemic dilated cardiomyopathy

AimsGenotype and left ventricular scar on cardiac magnetic resonance (CMR) are increasingly recognized as risk markers for adverse outcomes in non‐ischaemic dilated cardiomyopathy (DCM). We investigated the combined influence of genotype and late gadolinium enhancement (LGE) in assessing prognosis in a large cohort of patients with DCM.Methods and resultsOutcomes of 600 patients with DCM (53.3 ± 14.1 years, 66% male) who underwent clinical CMR and genetic testing were retrospectively analysed. The primary endpoints were end‐stage heart failure (ESHF) and malignant ventricular arrhythmias (MVA). During a median follow‐up of 2.7 years (interquartile range 1.3–4.9), 24 (4.00%) and 48 (8.00%) patients had ESHF and MVA, respectively. In total, 242 (40.3%) patients had pathogenic/likely pathogenic variants (positive genotype) and 151 (25.2%) had LGE. In survival analysis, positive LGE was associated with MVA and ESHF (both, p < 0.001) while positive genotype was associated with ESHF (p = 0.034) but not with MVA (p = 0.102). Classification of patients according to genotype (G+/G−) and LGE presence (L+/L−) revealed progressively increasing events across L−/G−, L−/G+, L+/G− and L+/G+ groups and resulted in optimized MVA and ESHF prediction (p < 0.001 and p = 0.001, respectively). Hazard ratios for MVA and ESHF in patients with either L+ or G+ compared with those with L−/G− were 4.71 (95% confidence interval: 2.11–10.50, p < 0.001) and 7.92 (95% confidence interval: 1.86–33.78, p < 0.001), respectively.ConclusionClassification of patients with DCM according to genotype and LGE improves MVA and ESHF prediction. Scar assessment with CMR and genotyping should be considered to select patients for primary prevention implantable cardioverter‐defibrillator placement.

Development and validation of a nomogram to predict the risk of death within 1 year in patients with non-ischemic dilated cardiomyopathy: a retrospective cohort study

Predicting the chances mortality within 1 year in non-ischemic dilated cardiomyopathy patients can be very useful in clinical decision-making. This study has developed and validated a risk-prediction model for identifying factors contributing to mortality within 1 year in such patients. The predictive nomogram was constructed using a retrospective cohort study, with 615 of patients hospitalized in the First Affiliated Hospital of Guangxi Medical University between October 2012 and May 2020. A variety of factors, including presence of comorbidities, demographics, results of laboratory tests, echocardiography data, medication strategies, and instances of heart transplant or death were collected from electronic medical records and follow-up telephonic consultations. The least absolute shrinkage and selection operator and logistic regression analyses were used to identify the critical clinical factors for constructing the nomogram. Calibration, discrimination, and clinical usefulness of the predictive model were assessed using the calibration plot, C-index and decision curve analysis. Internal validation was assessed with bootstrapping validation. Among the patients from whom follow-up data were obtained, the incidence of an end event (deaths or heart transplantation within 1 year) was 171 cases per 1000 person-years (105 out of 615). The main predictors included in the nomogram were pulse pressure, red blood cell count, left ventricular end-diastolic dimension, levels of N-terminal pro b-type natriuretic peptide, medical history, in-hospital worsening heart failure, and use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The model showed excellent discrimination with a C-index of 0.839 (95% CI 0.799–0.879), and the calibration curve demonstrated good agreement. The C-index of internal validation was 0.826, which demonstrated that the model was quite efficacious. A decision curve analysis confirmed that our nomogram was clinically useful. In this study, we have developed a nomogram that can predict the risk of death within 1 year in patients with non-ischemic dilated cardiomyopathy. This will be useful in the early identification of patients in the terminal stages for better individualized clinical decisions.

Late gadolinium enhancement is a strong predictor of life threatening arrhythmias in patients with non-ischemic dilated cardiomyopathy undergoing ICD implantation for primary prevention of sudden card

Abstract Funding Acknowledgements Type of funding sources: None. Background The usefulness of implantable cardioverter defibrillators (ICD) for primary prevention of arrhythmic sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM) has been questioned. Efforts to improve risk stratification have included scores such as the ‘MADIT-ICD benefit score’, and the use of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). The purpose of this study was to evaluate the potential usefulness of these two tools to assess the risk of life-threatening arrhythmias in patients with non-ischemic DCM undergoing ICD implantation for primary prevention of SCD. Methods We conducted a single-center retrospective study of consecutive patients who underwent contrast-enhanced CMR before ICD implantation for primary prevention of SCD. Patients with ischemic cardiomyopathy were used as reference. Patients with non-dilated cardiomyopathies were excluded. The arrhythmic component of the MADIT-ICD benefit score (VT/VF score) was calculated for each patient, and considered high if ≥ 7, as recommended. The primary endpoint was the occurrence of SCD or life-threatening arrhythmias (VF or VT &amp;gt;200 bpm). Follow-up was performed by device interrogation in all patients except those who suffered SCD. Results A total of 151 patients (93 ischemic, mean age 62±13 years, 75% male) with mean left ventricular ejection fraction (LVEF) of 27±8% were included. Overall, 72% (n=67) ischemic and 45% (n=26) non-ischemic patients had scores ≥ 7 and were considered high-risk. LGE was present in all patients with ischemic cardiomyopathy, and in 76% (n=44) of patients with non-ischemic DCM. During a median follow-up of 21 (8-38) months, 21 patients (13.9%, 11 ischemic and 10 non-ischemic) met the primary endpoint. Overall, the event-free survival of non-ischemic patients was similar to that of ischemic patients (log rank p=0.269) – Fig 1A. In patients with non-ischemic DCM, there were 7 arrhythmic events (26.9%) in those with MADIT-ICD VT/VF scores ≥7, and 3 events (9.4%) in those with scores &amp;lt;7 (log rank p= 0.104) – Fig 1B. In the same population, there were 10 arrhythmic events (23%) in patients with LGE, but no events in patients without LGE (log rank p=0.036) – Fig 1C. LVEF was similar in patients with and without arrhythmic events (26±8% vs. 27±7%, p=0.717), and in those with and without LGE (26±7% vs. 28±9%, p=0.342). Conclusion The presence of LGE is a strong predictor of life threatening arrhythmias in patients in non-ischemic DCM undergoing ICD implantation for primary prevention, seemingly outperforming the clinical MADIT-ICD benefit score.

Long-term impact of activation circuit-based ventricular tachycardia ablation on ventricular arrhythmia burden

Abstract Funding Acknowledgements Type of funding sources: None. Background Ventricular arrhythmias (VA) are a major cause of morbidity and mortality in heart failure patients. Ventricular tachycardia (VT) ablation is an established treatment for the reduction of recurrent implantable cardioverter-defibrillator (ICD) therapies in this population. In patients with substrate-related VT, mapping of the entire tachycardia circuit, when feasible, may allow for more accurate targeting of the clinical VT. Purpose To assess the long-term impact of catheter ablation based on activation mapping of substrate-related VT on VA burden. Methods Consecutive patients submitted to VT ablation between January 2013 and October 2021 were included. A comprehensive review of clinical records and device monitoring was performed to assess VA burden, defined as all ICD therapies and clinically documented VTs, before and after ablation. The primary outcome was reduction in the overall burden of VA after ablation. The impact of ablation on VA burden was assessed by fixed-effects Poisson regression; comparison at fixed time intervals was performed with a paired-sample Wilcoxon signed-rank test (STATA 12, JASP). Results A total of 134 VT ablation procedures were performed during the study period. Of these, there were 21 procedures where complete mapping of the VT activation circuit was achieved, corresponding to 18 patients. Mean age was 56.7 years, 88% male sex, mean left ventricular ejection fraction 39 ± 13%, BNP 540 ± 627 pg/mL. Etiology was ischemic in 44%, non-ischemic dilated cardiomyopathy in 39%, arrhythmogenic right ventricular dysplasia in 11% and hypertrophic cardiomyopathy in 6%. Mechanical support was in situ in 3 patients (two with temporary VA ECMO and one with LVAD as destination therapy); all but one patient had an ICD. Procedural duration was 209 ± 61 minutes. One patient developed complete AV block; no other peri-procedural complications were observed. During follow-up two patients died due to heart failure, one patient died from refractory cardiogenic shock with refractory incessant VT and one patient underwent orthotopic heart transplant. The mean follow-up time after ablation was 2.2 ± 1.9 years. A significant reduction in VA burden was observed (Figure 1) at 3 months (92.5% reduction, p=0.002) and 6 months after ablation (83.3% reduction, p=0.041). After fixed-effects Poisson regression, there was an estimated long-term reduction of 75% (CI 12-93%, p=0.031) of VA burden after VT circuit ablation. Conclusion Targeted circuit ablation is feasible in a subset of patients referred to VT ablation and leads to a significant sustained decrease in VA burden and device therapies.

Delayed detection programming significantly reduces inappropriate ICD therapies in patients with left-ventricular assist devices

Abstract Funding Acknowledgements Type of funding sources: None. Background Implantation of a left ventricular assist device (LVAD) is an established therapy for end-stage heart failure, either as bridge to transplantation or as destination therapy. Virtually all LVAD patients carry an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention. The risk of ventricular tachyarrhythmias is significant in LVAD patients, but so is the burden of supraventricular tachycardia and the ensuing risk of inappropriate ICD therapies. The present retrospective study sought to quantify the impact of standard ICD programming vs. a ICD programming with long detection delays on the occurrence of inappropriate ICD therapies. Methods and results We retrospectively identified 337 consecutive patients (292 male, mean age 54.2 ± 12.3 years) who received a continuous-flow LVAD at our institution. Median follow-up duration was 2.3 (IQR 1.3, 3.7) years. Heart failure etiology was ischemic cardiomyopathy in 155 patients (46.0 %) and non-ischemic dilated cardiomyopathy in 150 (44.5 %). Other etiologies accounted for 32 patients (9.4 %). ICDs implanted at the time of LVAD implantation were single chamber devices in 176 patients (52.2 %), dual chamber devices in 45 patients (13.4 %), and CRT-D in 116 patients (34.4 %) A total of 2228 ICD-treated arrhythmia episodes occurred in 153 patients. 2066 (92.6 %) episodes were appropriate interventions for ventricular arrhythmias. 162 (7.3 %) treatments were inappropriate due to supraventricular tachyarrhythmias (n=115; 71.4 %), sinus tachycardia (n=15; 9.3 %) or oversensing (n=21; 12.9%). We retrospectively compared a standard programming (number of intervals for detection [NID] in the slowest therapy zone ≤ 40) and a long delay programming (NID &amp;gt; 40) and investigated the time to the first inappropriate therapy. A total of 285 patients were programmed to NID ≤ 40 at the first ICD interrogation after LVAD implant, 47 were programmed to NID &amp;gt; 40. Therapies were inactive in the remaining 5 patients. Median NID was 30 (IQR 23, 35) in the standard programming group and 60 (IQR 50, 76) in the long delay group, with similar rates for detection (median cycle lengths 340 [IQR 330, 350] ms and 330 [IQR 322, 340] ms for standard and long delay, respectively). Long delay programming was associated with significantly higher freedom from inappropriate therapies during follow-up (Hazard ratio 0.14, p [log rank] 0.027). No significant difference was observed between groups with regard to time to first appropriate therapy. Conclusion A number of intervals for detection greater than 40 in the slowest therapy zone was associated with a significantly increased freedom from inappropriate therapies in this large retrospective single-center cohort of LVAD patients with an ICD and should be considered as the default ICD programming strategy in this population.

Epicardial mapping as first intention approach for structural ventricular tachycardia ablation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In several structural arrhythmogenic diseases that comprise intricate endocardial, intramural and epicardial substrates, endocardial ablation of ventricular tachycardia (VT) is not sufficient and epicardial ablation has lately become a complementary and necessary tool. Purpose To evaluate the clinical characteristics of patients (pts) most suitable for first intention epicardial VT ablation. Methods Single-center prospective study of consecutive pts with structural heart disease undergoing first intention epicardial VT mapping between August 2015 and June 2021. Decision for epicardial approach was based on the etiology, VT electrocardiogram (ECG) and cardiac magnetic resonance (CMR) results. Under general anesthesia, subxiphoid access using a Tuhoy needle was done using fluoroscopic guidance and with high-density epicardial mapping was performed. Epicardial ablation was performed if relevant arrhythmogenic findings were locally confirmed. Results First intention epicardial VT ablation was attempted in 18 pts (mean age 59.8±12 years,94% male) of whom 16 had non-ischemic dilated cardiomyopathy (NICM,idiopathic:11; post-myocardis:4; hereditary:1) and 2 had right ventricular arrhythmogenic cardiomyopathy. Mean LVEF was 33% and 79% had a previous ICD (53% in primary prevenon). 69% were referred for ablation due to arrhythmic storm (1pt in cardiogenic shock). Epicardial access was achieved in 17 pts (94%), without acute complications. In 35% pts with NICM the decision for epicardial approach was based on the detection of subepicardial CMR delayed-hyperenhancement and relevant epicardial arrhythmic substrate was confirmed by mapping in all cases. In 3 pts radiofrequency (RF) applicaons were not performed at epicardium, as no abnormal electrograms were locally detected, and an addional endocardial approach was prosecuted. The mean overall procedure and fluoroscopic time were 123 and 28min, respectively, with a mean RF application me of 51min. After the procedure 1pt required pericardial drainage due to inflammatory pericardial effusion. No other acute complications occurred. During a mean follow-up of 2.8±1.8 years, only 3pts (17%) had VT recurrence; 5pts (28%) died due to end-stage heart failure and 2pts (11%) underwent heart transplantation. Conclusion In NICM a first intention epicardial VT ablation performed by experienced operators/centers is efficient, particularly if guided by CMR findings,and presents a safety profile.

The outcome spectrum for Dilated Cardiomyopathy and Ventricular Tachycardia: results from the prospective, multicenter, DCM-VT ablation study

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The study was partially supported by an investigator initiated grant from Biosense Webster (a Johnson &amp; Johnson company) Background Recurrent sustained ventricular tachycardia (VT) due to nonischemic dilated cardiomyopathy (DCM) is difficult to treat and long-term outcome data are limited. Objective We aimed to identify predictors for mortality or heart transplantation (MHT) and VT recurrence. Methods Consecutive DCM patients accepted for VT catheter ablation (RFCA) in 9 centers were prospectively enrolled and followed. Results Of 281 consecutive patients (age 60±13yrs, 85% men, LVEF 36±12%) 35% had VT storm, 20% incessant VT, and 68% failed amiodarone. During a median follow-up of 21 (IQR 6-30) months after RFCA (epicardial in 58%, no RFCA due to inaccessible target in 6.4%), 67(24%) patients died/underwent HT and 138(49%) had VT recurrence (45 within 30 days defined as early); the cumulative 4-year rate of VT or MHT was 70% and of MHT 38%. In multivariable analysis predictors of MHT were early VT recurrence (HR 2.92 (CI1.37-6.21), p&amp;lt;0.01), amiodarone at discharge (HR 3.23 (CI1.43-7.33, p&amp;lt;0.01), renal dysfunction (HR 1.92 (CI1.01-3.64), p=0.046), and LVEF (HR 1.36 (CI 1.0-1.84), p=0.052). A LVEF ≤32% was the optimal threshold to identify patients at risk for MHT (AUC 0.75). MHT per 100 person-years was 40.4 after early VT recurrence and significantly higher, compared to 14.2 after later VT recurrence and to 8.5 after RFCA with no VT recurrence (both p&amp;lt;0.01). Mortality rates for patients with VT recurrence after 30 days were not significantly higher than for patients with no VT recurrences Patients with early recurrence and LVEF≤32% had a 1-year MHT rate of 55% (figure). VT recurrence was predicted by prior ICD shocks, basal antero-septal VT origin, and procedural failure but not LVEF. Conclusion DCM patients needing RFCA for VT are a high-risk group. Following RFCA half remain free of VT recurrences. Early VT recurrence with LVEF&amp;lt;0.32 identifies those with a very high risk and screening for mechanical support/ HT should be considered. Late VT recurrence after RFCA does not predict worse outcome.

Transient versus persistent improved ejection fraction in non-ischaemic dilated cardiomyopathy.

The recent definition of heart failure with improved ejection fraction outlined the importance of the longitudinal assessment of left ventricular ejection fraction (LVEF). However, long-term progression and outcomes of this subgroup are poorly explored. We sought to assess the LVEF trajectories and their correlations with outcome in non-ischaemic dilated cardiomyopathy (NICM) with improved ejection fraction (impEF). Consecutive NICM patients with baseline LVEF ≤40% enrolled in the Trieste Heart Muscle Disease Registry with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, and second evaluation showing both a ≥10% point increase from baseline LVEF and LVEF >40%. Transient impEF was defined by the documentation of recurrent LVEF ≤40% during follow-up. The primary endpoint was a composite of all-cause death, heart transplantation and left ventricular assist device (D/HT/LVAD). Among 800 patients, 460 (57%) had impEF (median time to improvement 13 months). Transient impEF was observed in 189 patients (41% of the overall impEF group) and was associated with higher risk of D/HT/LVAD compared with persistent impEF at multivariable analysis (hazard ratio 2.54; 95% confidence interval 1.60-4.04). The association of declining LVEF with the risk of D/HT/LVAD was non-linear, with a steep increase up to 8% points reduction, then remaining stable. In NICM, a 57% rate of impEF was observed. However, recurrent decline in LVEF was observed in ≈40% of impEF patients and it was associated with an increased risk of D/HT/LVAD.

PO-693-06 LATE GADOLINIUM ENHANCEMENT IS A STRONG PREDICTOR OF LIFE-THREATENING ARRHYTHMIAS IN PATIENTS WITH NON-ISCHEMIC DILATED CARDIOMYOPATHY UNDERGOING ICD IMPLANTATION FOR PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH

The usefulness of implantable cardioverter defibrillators (ICD) for primary prevention of arrhythmic sudden cardiac death (SCD) in patients with non-ischemic dilated cardiomyopathy (DCM) has been questioned. Efforts to improve risk stratification have included scores such as the ‘MADIT-ICD benefit score’, and the use of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). The purpose of this study was to evaluate the potential usefulness of these two tools to assess the risk of life-threatening arrhythmias in patients with DCM undergoing ICD implantation for primary prevention of SCD. We conducted a single-center retrospective study of consecutive patients who underwent CMR before ICD implantation for primary prevention of SCD. Patients with non-dilated cardiomyopathies were excluded.The arrhythmic component of the MADIT-ICD benefit score (VT/VF score) was calculated, and considered high if ≥ 7, as recommended. The primary endpoint was the occurrence of SCD or life-threatening arrhythmias (VF or VT >200 bpm). Follow-up was performed by device interrogation in all patients except those who suffered SCD. A total of 151 patients (93 ischemic, mean age 62±13 years, 75% male) with mean left ventricular ejection fraction (LVEF) of 27±8% were included. LGE was present in all patients with ischemic cardiomyopathy, and in 76% (n=44) of patients with DCM. During a median of 21 (8-38) months, 21 patients (13.9%, 11 ischemic and 10 DCM) met the primary endpoint. The event-free survival of DCM patients was similar to that of ischemic patients (log rank p=0.269) - Fig 1A. In patients with DCM, there were 7 arrhythmic events (26.9%) in those with MADIT-ICD VT/VF scores ≥7, and 3 (9.4%) in those with scores <7 (log rank p= 0.104) - Fig 1B. In the same population, there were 10 arrhythmic events (23%) in patients with LGE, but no events in patients without LGE (log rank p=0.036) - Fig 1C. LVEF was similar in patients with and without arrhythmic events (26±8% vs. 27±7%, p=0.717), and in those with and without LGE (26±7% vs. 28±9%, p=0.342). The presence of LGE is a strong predictor of life-threatening arrhythmias in patients in non-ischemic DCM undergoing ICD implantation for primary prevention, seemingly outperforming the clinical MADIT-ICD benefit score.

MR -specific characteristics of left ventricular noncompaction and dilated cardiomyopathy

BackgroundThe differentiation of dilated cardiomyopathy (DCM) and left ventricular noncompaction (LVNC) is a recurring issue during cardiac imaging processes; thus, we aimed to compare the left ventricular (LV) cardiac MRI characteristics of these patients. MethodsThirty-one nonischemic DCM patients, 42 LVNC patients with reduced ejection fraction and 42 healthy controls were included in this retrospective study. LV volumetric, functional and myocardial mass parameters were measured with a threshold-based technique, while global and segmental strain values and rotational patterns were analyzed with feature-tracking strain analysis. ResultsOf the LV volumetric and myocardial mass parameters, only the trabeculated and papillary muscle mass (TPMi) values differed significantly between the patient groups and were higher in the LVNC group (DCM vs LVNC: 43.2 ± 8.9 vs 51.6 ± 13.6 g/m2, p < 0.002). The global longitudinal and circumferential strains were similar between the patient groups and significantly worse than those of the controls. In comparing the segmental strains between the patient groups, only the circumferential apical strain was significantly lower in the LVNC group (DCM vs LVNC: −30.5 ± 13.5 vs −24.5 ± 12.0%, p < 0.05). There was no difference in the rotational pattern between the patient groups, and both healthy and patient populations showed heterogeneous rotational patterns. ConclusionsDespite the similarities between DCM and LVNC in volumetric, global strain parameters, and rotational patterns, we found some differences between the patient groups, as the TPMi was higher and the apical circumferential strains were significantly lower in LVNC. These minor alterations might be due to the morphological characteristics of LVNC with a trabeculated apical region.

Reverse cardiac remodeling after fluid balance optimization in patients with end-stage renal disease.

BackgroundIn patients with end‐stage renal disease (ESRD) undergoing hemodialysis, cardiovascular diseases, and in particular chronic heart failure are the leading causes of morbidity and mortality. Nevertheless, few data are available about the impact of fluid optimization on echocardiographic parameters of cardiac function in patients with ESRD.Methods and ResultsIn five patients with ESRD undergoing hemodialysis who had developed nonischemic dilated cardiomyopathy, an optimal fluid volume management based on a strict bioelectrical impedance analysis‐assisted dry weight target and dietary sodium and water restriction led to left ventricular reverse remodeling and improvement in hemodynamic parameters. The reverse remodeling further improved after kidney transplantation.ConclusionsThis case series supports the possible beneficial effect of volume status optimization on cardiac function and the potential reversibility of cardiac dysfunction after kidney transplantation.

Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial.

Optimal timing for catheter ablation of ventricular tachycardia is an important unresolved issue. There are no randomized trials evaluating the benefit of ablation after the first implantable cardioverter defibrillator (ICD) shock. We conducted a 2-phase, prospective, multicenter, randomized clinical trial. Patients with ischemic or nonischemic dilated cardiomyopathy and primary or secondary prevention indication for ICD were enrolled in an initial observational phase until first appropriate shock (phase A). After reconsenting, patients were randomly assigned 1:1 in phase B to immediate ablation (within 2 months from shock delivery) or continuation of standard therapy. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. Amiodarone intake was not allowed except for documented atrial tachyarrhythmias. On July 23, 2021, phase B of the trial was interrupted as a result of the first interim analysis on the basis of the Bayesian adaptive design. Of the 517 patients enrolled in phase A, 154 (30%) had ventricular tachycardia, 56 (11%) received an appropriate shock over a median follow-up of 2.4 years (interquartile range, 1.4-4.4), and 47 of 56 (84%) agreed to participate in phase B. After 24.2 (8.5-24.4) months, the primary end point occurred in 1 of 23 (4%) patients in the ablation group and 10 of 24 (42%) patients in the control group (hazard ratio, 0.11 [95% CI, 0.01-0.85]; P=0.034). The results met the prespecified termination criterion of >99% Bayesian posterior probability of superiority of treatment over standard therapy. No deaths were observed in the ablation group versus 8 deaths (33%) in the control group (P=0.004); there was 1 worsening heart failure hospitalization in the ablation group (4%) versus 4 in the control group (17%; P=0.159). ICD shocks were less frequent in the ablation group (9%) than in the control group (42%; P=0.039). Ventricular tachycardia ablation after first appropriate shock was associated with a reduced risk of the combined death or worsening heart failure hospitalization end point, lower mortality, and fewer ICD shocks. These findings provide support for considering ventricular tachycardia ablation after the first ICD shock. URL: https://www. gov; Unique identifier: NCT01547208.

Bridge to Transplant with Durable Left Ventricular Assist Device is Associated with Primary Graft Dysfunction Following Heart Transplantation: A Report from the International Consortium on Primary Graft Dysfunction

<h3>Purpose</h3> The International Consortium on Primary Graft Dysfunction is a multicenter, prospective observational study that has collected data on over 2700 HT recipients to identify clinical risk factors for PGD in the contemporary era. The objective of this study was to determine whether BTT with LVAD is associated with PGD and, if so, to identify the high-risk features of BTT recipients. <h3>Methods</h3> We collected data from 10 participating sites in Europe, the United States (US), and Canada including donor and recipient demographics, pre- and post-HT hemodynamics, and type and duration of BTT durable LVAD support prior to HT. The primary outcome was ISHLT defined severe PGD. Rates of PGD were compared between BTT and medically managed recipients. Univariate and multivariate logistic regression was performed to identify clinical characteristics associated with an increased risk of PGD in the BTT population. <h3>Results</h3> Data from 2763 HT recipients from the consortium were included, 837 recipients were BTT. ISHLT severe PGD was seen in 215 (7.8%). The incidence of PGD was significantly higher in BTT recipients as compared with those who were medically managed (13.6% v. 6.3%, p<0.001). Using data only from BTT recipients, univariate logistic regression identified recipient age, geographic location of transplant, dialysis prior to HT, dilated cardiomyopathy, and CVP/PCWP ratio as significant risk factors for severe PGD. Results of the multivariable model are shown in the Table, where recipient age, location of HT, and CVP/PCWP remained significant. <h3>Conclusion</h3> BTT with durable LVAD is associated with an increased risk of severe PGD in the contemporary era. High-risk features for PGD in BTT recipients include pre-transplant renal failure, RV dysfunction as quantified by CVP/PCWP ratio, HT within the United States, and non-ischemic dilated cardiomyopathy.

Intermittent Levosimendan for Late Right Ventricular Failure in Patients with Left Ventricular Assist Devices

<h3>Purpose</h3> Implantable continuous flow left ventricular assist devices (LVADs) are increasingly used in end-stage heart failure as a bridge-to-transplant (BTT) or destination therapy (DT). One of its most common pitfalls is the development of right ventricular (RV) failure. Despite the fact that right heart failure remains an independent risk factor for mortality, evidence-based therapies are still lacking. The aim of the study is to describe our preliminary single center experience using intermittent infusion of levosimendan in patients with late right heart failure post LVAD implantation. <h3>Methods</h3> We retrospectively revised the data of all patients who received an LVAD in our center and evaluated the patient characteristics and outcomes of those treated with levosimendan for late RV failure. <h3>Results</h3> In the past 10 years (from 2011 until 2020), a total of 130 patients received an LVAD and 8 of them were treated with intermittent levosimendan for RV failure (3 females and 5 males). Two patients had a HeartMate 2 (HM2) and six a HeartMate 3 (HM3). The mean age at LVAD implantation was 59 years and the etiology of their heart failure was coronary artery disease (4/8), myocarditis (2/8) or a non-ischemic dilated cardiomyopathy (2/8). All patients received a monthly dose between 0.1 and 0.3 mcg/kg/min. The average duration of levosimendan therapy during our follow-up was 12 months (ranged from 4 to 26 months). Two patients died because of multi-organ failure due to progression of RV failure, while one of them also suffered hemolysis and several gastrointestinal bleedings. One patient was successfully bridged to a heart transplant (after 13 months of levosimendan therapy), but unfortunately died directly after surgery due to acute graft failure. In one other patient, levosimendan was stopped at the request of the patient based on a subjective lack of efficacy and one episode of ventricular tachycardia. The four remaining patients continue their intermittently therapy and are still alive (2 waiting for the availability of a heart transplant, while the other two have LVAD as destination therapy). <h3>Conclusion</h3> In this first case series, the intermittent use of levosimendan looks promising for the treatment of late RV failure after LVAD.