Septal Midwall Late Gadolinium Enhancement in Ischemic Cardiomyopathy and Nonischemic Dilated Cardiomyopathy-Characteristics and Prognosis.

Septal midwall late gadolinium enhancement (LGE) is a characteristic finding on cardiac magnetic resonance imaging (CMR) in nonischemic dilated cardiomyopathy (DCM) and is associated with adverse events. Its significance in ischemic cardiomyopathy (ICM) is unknown. With this multicenter observational study, we aimed to study the characteristics of septal midwall LGE and evaluate its prognostic value in ICM. A total of 1,084 patients with an impaired left ventricular (LV) ejection fraction (<50%) on LGE-CMR, either because of ICM (53%) or DCM, were included retrospectively. Septal midwall LGE was defined as midmyocardial stripe-like or patchy LGE in septal segments and was present in 10% of patients with ICM compared with 34% of patients with DCM (p <0.001). It was significantly associated with larger LV volumes and lower LV ejection fraction, irrespective of etiology. The primary endpoint was all-cause mortality and secondary endpoint was ventricular arrhythmias (VAs), including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter-defibrillator (ICD) therapy. During a median follow-up of 2.7 years, we found a significant association between septal midwall LGE and mortality in patients with DCM (hazard ratio [HR] 1.92, p = 0.03), but not in patients with ICM (HR 1.35, p = 0.39). Risk of VAs was significantly higher in patients with septal midwall LGE on CMR, both in DCM (HR 2.80, p <0.01) and in ICM (HR 2.70, p <0.01). In conclusion, septal midwall LGE, typically seen in DCM, was also present in 10% of patients with ICM and was associated with increased LV dilation and worse function, irrespective of etiology. When present, septal midwall LGE was associated with adverse outcome.

Recurrent ventricular arrhythmias and mortality in cardiac arrest survivors with a reversible cause with and without an implantable cardioverter defibrillator: A systematic review.

BACKGROUND: Sudden cardiac arrest survivors with a reversible cause are not eligible for implantable cardioverter defibrillator (ICD) implantation. This study aims to evaluate the risk of recurrent ventricular arrhythmia in sudden cardiac arrest survivors with a reversible cause and evaluate if ICD implantation increases survival. METHODS: We conducted a systematic review to identify studies evaluating ICD implantation in sudden cardiac arrest survivors with a reversible cause. Outcomes were mortality and appropriate device therapy. Sudden cardiac arrest patients were divided into 4 subgroups: due to acute myocardial infarction; due to coronary artery spasm; due to takotsubo cardiomyopathy; and studies with various reversible causes of cardiac arrest. RESULTS: 27 studies were included, evaluating 11,402 patients. A total of 2570 patients received an ICD. Studies evaluating coronary artery spasm and with various reversible causes showed a relatively high rate of appropriate device therapy (17% and 20%) and described an increased survival in ICD patients. Takotsubo cardiomyopathy was associated with a low mortality and none of the ICD patients received appropriate device therapy. Studies evaluating acute myocardial infarction survivors reported inconsistent results, with high numbers of appropriate device therapy (12-66%), but the mortality-rate of patients with and without an ICD varied. CONCLUSION: This study shows that the recurrence risk of ventricular arrhythmia varies between different reversible causes of sudden cardiac arrest and should not be evaluated as one entity. Cardiac arrest survivors with a reversible cause can be at risk of recurrent ventricular arrhythmia and selected patients may benefit from ICD implantation.

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients.

AIMS: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. METHODS AND RESULTS: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4-4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex-specific pattern in ADT. CONCLUSIONS: Male ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non-ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex-specific relation to ventricular arrhythmias. As a consequence, sex-specific risk stratification models of SCD using commonly available clinical parameters could not be derived.

Reversible Cause of Cardiac Arrest and Secondary Prevention Implantable Cardioverter Defibrillators in Patients With Coronary Artery Disease: Value of Complete Revascularization and LGE-CMR.

Background In survivors of sudden cardiac arrest with obstructive coronary artery disease, it remains challenging to distinguish ischemia as a reversible cause from irreversible scar-related ventricular arrhythmias. We aimed to evaluate the value of implantable cardioverter-defibrillator (ICD) implantation in sudden cardiac arrest survivors with presumably reversible ischemia and complete revascularization. Methods and Results This multicenter retrospective cohort study included 276 patients (80% men, age 67±10 years) receiving ICD implantation for secondary prevention. Angiography was performed before ICD implantation. A subgroup of 166 (60%) patients underwent cardiac magnetic resonance imaging with late gadolinium enhancement before implantation. Patients were divided in 2 groups, (1) ICD-per-guideline, including 228 patients with incomplete revascularization or left ventricular ejection fraction ≤35%, and (2) ICD-off-label, including 48 patients with complete revascularization and left ventricular ejection fraction >35%. The primary outcome was time to appropriate device therapy (ADT). During 4.0 years (interquartile range, 3.5-4.6) of follow-up, ADT developed in 15% of the ICD-off-label group versus 43% of the ICD-per-guideline group. Time to ADT was comparable in the ICD-off-label and ICD-per-guideline groups (hazard ratio (HR), 0.46; P=0.08). No difference in mortality was observed (HR, 0.95; P=0.93). Independent predictors of ADT included age (HR, 1.03; P=0.01), left ventricular end-diastolic volume HR, (1.05 per 10 mL increase; P<0.01) and extent of transmural late gadolinium enhancement (HR, 1.12; P=0.04). Conclusions This study demonstrates that sudden cardiac arrest survivors with coronary artery disease remain at high risk of recurrent ventricular arrhythmia, even after complete revascularization and with preserved left ventricular function. Late gadolinium enhancement-cardiac magnetic resonance imaging derived left ventricular volumes and extent of myocardial scar were independently associated with.

Characteristics and prognostic value of right ventricular (dys)function in patients with non-ischaemic dilated cardiomyopathy assessed with cardiac magnetic resonance imaging.

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.

Value of CMR and PET in Predicting Ventricular Arrhythmias in Ischemic Cardiomyopathy Patients Eligible for ICD.

OBJECTIVES: This study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs). BACKGROUND: Improved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking. METHODS: Seventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [15O]H2O and [11C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated. RESULTS: In total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA. CONCLUSIONS: In patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.

Correlation between septal midwall late gadolinium enhancement on CMR and conduction delay on ECG in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Septal midwall late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is a characteristic finding in nonischemic dilated cardiomyopathy (DCM) and is associated with adverse cardiac events. QRS-prolongation in DCM is also frequently present and a predictor of arrhythmic events and mortality. Since the His-Purkinje fibres are located in the interventricular septum, QRS-prolongation may directly result from septal fibrosis, visualized by LGE. Our aim was to study the correlation of the presence and extent of septal midwall LGE and QRS-duration. METHODS: DCM-patients with left ventricular (LV) dysfunction (LVEF < 50%) were included. LV volumes, systolic function and nonischemic septal midwall LGE, defined as patchy or stripe-like LGE in the septal segments, were quantified. QRS-duration on standard 12-lead ECG was measured. RESULTS: 165 DCM-patients were included (62% male, mean age 59 ± 15 years) with a median LVEF of 36% [24-44]. Fifty-one patients (31%) demonstrated septal midwall LGE with a median extent of 8.1 gram [4.3-16.8]. Patients with midwall LGE had increased LV end-diastolic volumes (EDV) 248 mL [193-301] vs. 193 mL [160-239], p < 0.001) and lower LVEF (26% [18-35] vs. 40% [32-45], p < 0.001). Median QRS-duration was 110 ms [95-146] without a correlation to the presence nor extent of midwall LGE. QRS-duration was moderately correlated with LV-dilation and mass (respectively r = 0.35, p < 0.001 and r = 0.30, p < 0.001). CONCLUSION: In DCM-patients, QRS-prolongation and septal midwall LGE are frequently present and often co-exist. However, they are not correlated. This suggests that the assessment of LGE-CMR has complementary value to ECG evaluation in the clinical assessment and risk stratification of DCM-patients.

The Prognostic Value of Late Gadolinium-Enhanced Cardiac Magnetic Resonance Imaging in Nonischemic Dilated Cardiomyopathy: A Review and Meta-Analysis.

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