Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. METHODS AND RESULTS: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. CONCLUSION: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC.

Ventricular Arrhythmias and Sudden Death in Nonischemic Dilated Cardiomyopathy: Matter of Sex or Scar?

BACKGROUND: To evaluate the association between sex and ventricular arrhythmias (VA) or sudden death (SD) in nonischemic dilated cardiomyopathy, including analysis of potential confounders. METHODS AND RESULTS: Retrospective cohort study of consecutive patients with DCM referred for cardiac magnetic resonance at 2 tertiary hospitals. The primary combined end point encompassed sustained VA, appropriate implantable cardioverter defibrillator therapies, resuscitated cardiac arrest, and SD. We included 1165 patients with median follow-up of 36 months (interquartile range 20-58 months). The majority of patients (66%) were males. Males and females had similar left ventricular ejection fraction, but the prevalence of late gadolinium enhancement (LGE) at cardiac magnetic resonance was significantly higher among males (48% vs 30%, P < .001). Males had higher cumulative incidence of the primary end point (8% vs 4%, P = .02), and male sex was a significant predictor of the primary end point at univariate analysis (hazard ratio 1.93, P = .02). However, LGE had a major confounding effect in the association between sex and the primary outcome: the hazard ratio of male sex adjusted for LGE was 1.29 (P = .37). LGE+ females had significantly higher cumulative incidence of the primary end point than LGE- males (13% vs 1.8%, P < .001). CONCLUSIONS: In patients with DCM, the prevalence of LGE is significantly higher among males, implying a major confounding effect in the association between male sex and VA or SD. LGE+ females have significantly higher risk than LGE- males. These data do not support the inclusion of sex into risk stratification algorithms for VA or SD in DCM.

Revascularization of coronary chronic total occlusions in an infarct-related artery and recurrence of ventricular arrhythmias among patients with secondary prevention implantable cardioverter defibrillator.

OBJECTIVES: To evaluate whether the revascularization of a coronary chronic total occlusion in an infarct-related artery (IRACTO) may be associated with lower recurrence of ventricular arrhythmias (VA) among patients with a secondary prevention implantable cardioverter defibrillator (ICD). BACKGROUND: IRACTO is increasingly recognized as an independent predictor of VA. It is unknown whether IRACTO revascularization can reduce the burden of VA. METHODS: Multicenter observational cohort study that included consecutive patients with prior myocardial infarction and secondary prevention ICD. The primary endpoint was any appropriate ICD therapy. RESULTS: Among the 460 patients included, 269 (58%) had at least one IRACTO at the coronary angiogram performed before ICD implantation; of these, 20 (7%) had their IRACTO successfully revascularized (IRACTO-R) afterwards. During a median follow-up of 48 months, 229 patients (49%) had at least one appropriate ICD therapy. Patients with IRACTO not revascularized (IRACTO-NR) had the highest incidence of ICD therapies (65%) while patients with IRACTO-R had the lowest (10%, p < .001). In the entire cohort, IRACTO-NR was an independent predictor of appropriate ICD therapies (HR 2.85, p < .001) and appropriate ICD shocks (HR 2.94, p < .001). Among patients with IRACTO at baseline, IRACTO-R was independently associated with a marked reduction of appropriate ICD therapies (HR 0.12, p = .002) and appropriate ICD shocks (HR 0.21, p = .03). CONCLUSIONS: In patients with prior myocardial infarction and secondary prevention ICD, IRACTO revascularization was independently associated with a markedly lower incidence of appropriate ICD therapies and shocks. These results should be corroborated by larger prospective studies.

Late potentials abolition reduces ventricular tachycardia recurrence after ablation especially in higher-risk patients with a chronic total occlusion in an infarct-related artery.

INTRODUCTION: Late potentials (LP) abolition is recognized as an effective strategy for substrate ablation of ventricular tachycardia (VT). The presence of a chronic total occlusion in a coronary artery responsible for a previous myocardial infarction (infarct related artery CTO, IRA-CTO) is emerging as a predictor of ventricular arrhythmias and VT recurrence after ablation. We sought to analyze the effects of LP abolition, focusing on the high-risk subgroup of patients with IRA-CTO. METHODS AND RESULTS: This was a single-center, observational study that screened all patients with prior myocardial infarction and clinical VT, referred for VT ablation at San Raffaele Hospital between 2010 and June 2013. Patients were then included in the study if they had a coronary diagnostic angiography (without revascularization) performed during the index hospitalization. The main endpoint was VT recurrence after ablation. Eighty-four patients formed the population of the study. An IRA-CTO was present in 47 patients (56%) and the presence of an IRA-CTO was a predictor of VT recurrence (HR 3.7, P = 0.005). LP were observed in 51 patients and successfully abolished in 38 cases. LP abolition was associated with lower VT recurrence especially among patients with IRA-CTO (24% vs. 65%, P = 0.005). The presence of an IRA-CTO, in combination with no LP abolition, was the strongest predictor of VT recurrence (HR 4.4, P < 0.001). CONCLUSIONS: Late potentials abolition is an effective strategy for substrate ablation of ventricular tachycardia. The additional reduction of VT recurrence achieved with LP abolition on top of noninducibility is especially significant among high-risk patients with IRA-CTO.

Chronic total occlusion in an infarct-related coronary artery and the risk of appropriate ICD therapies.

INTRODUCTION: Risk stratification for ventricular arrhythmias in patients with ischemic cardiomyopathy needs to be improved. Coronary chronic total occlusions in an infarct-related artery (IRA-CTOs) have been associated with an increased arrhythmic risk. This study aimed to evaluate the association between IRA-CTOs and appropriate implantable cardioverter-defibrillator (ICD) therapies. METHODS AND RESULTS: Observational cohort study that included 342 patients with ischemic cardiomyopathy, an ICD implanted for primary or secondary prevention, and a coronary angiography performed shortly before ICD implantation. The ICD was implanted for primary prevention in 163 patients (48%). IRA-CTO was found in 161 patients (47%). During a median follow-up of 33 months, 41% of patients experienced at least one appropriate ICD therapy. Patients with IRA-CTO had higher proportions of appropriate ICD therapies (57% vs. 26%, P < 0.001) and appropriate ICD shocks (40% vs. 17%, P < 0.001). At multivariate Cox regression, IRA-CTO was the only variable that consistently resulted as independent predictor of appropriate ICD therapies and shocks both in the global population of the study (HR 2.3, P < 0.001 and HR 3, P < 0.001, respectively) and when analyzing separately patients with primary or secondary prevention ICD. CONCLUSIONS: IRA-CTO is an independent predictor of appropriate ICD therapies, including appropriate ICD shocks. This association is consistent across all the subgroups analyzed. Patients with IRA-CTO have a very high risk of appropriate ICD therapies. These findings may help improving risk stratification as well as the management of ventricular arrhythmias in patients with ischemic cardiomyopathy.

Chronic total occlusion of an infarct-related artery: a new predictor of ventricular arrhythmias in primary prevention implantable cardioverter defibrillator patients.

Aims: The aim of this article is to evaluate the impact of a coronary chronic total occlusion in an infarct-related artery (IRA-CTO) on the occurrence of ventricular arrhythmias (VAs) in patients implanted with an implantable cardioverter defibrillator (ICD) for primary prevention. Methods and Results: The study includes a prospective cohort of 108 consecutive patients with ischaemic cardiomyopathy, in whom an ICD was implanted for primary prevention and a coronary angiography performed before ICD implantation. About 49 patients (45%) had a CTO and 34 (31%) had an IRA-CTO. Patients with IRA-CTO did not differ from the rest of the population in terms of basal characteristics and severity of cardiac disease. Median follow-up was 33 months (interquartile range 46). Infarct-related artery-CTO was associated with higher rates of any VA (53 vs. 26%, P = 0.006) and fast ventricular tachycardia (fast VT, cycle length <300 ms) or ventricular fibrillation (VF) (47 vs. 19%, P = 0.002). At multivariate Cox regression, IRA-CTO was the only independent predictor of any VA [hazard ratio (HR) 3.64, P = 0.002] and fast VT/VF (HR 3.36, P = 0.008). On the contrary, CTO not associated with a prior infarction in their territory did not increase the risk of VA. Infract-related artery-CTO was also an independent predictor of cardiac mortality or heart transplantation (HR 3.46, P = 0.022). Conclusion: In ischaemic patients implanted with an ICD for primary prevention, a CTO associated with a previous infarction in its territory is an independent predictor of VA and, especially, of fast VT/VF, identifying a subgroup of patients with a very high rate of arrhythmic events at follow-up.

Impact of previous cardiac surgery on long-term outcome of cavotricuspid isthmus-dependent atrial flutter ablation.

AIMS: The aim of this study was to determine the acute and long-term outcome of radiofrequency catheter ablation (RFCA) for cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) in adults with and without previous cardiac surgery (PCS), and predictors of these outcomes. Structural alterations of the anatomical substrate of the CTI-AFL are observed in post-operative patients, and these may have an impact on the acute success of the ablation and in the long-term. METHODS AND RESULTS: Clinical records of consecutive adults undergoing RFCA of CTI-AFL were analysed. Two main groups were considered: No PCS and PCS patients, who were further subdivided into acquired heart disease (AHD: ischaemic heart disease and valvular/mixed heart disease) and congenital heart disease [CHD: ostium secundum atrial septal defect (OS-ASD) and complex CHD]. Multivariate analysis identified clinical and procedural factors that predicted acute and long-term outcomes. A total of 666 patients (73% men, age 65 ± 12 years) were included: 307 of them with PCS. Ablation was successful in 647 patients (97%), 96% in the PCS group and 98% in the No PCS group (P = 0.13). Regression analysis showed that surgically corrected complex CHD was related to failure of the procedure [odds ratio 5.6; 95% confidence interval (CI) 1.6-18, P = 0.008]. After a follow-up of 45 ± 15 months, recurrences were observed in 90 patients (14%), more frequently in the PCS group: absolute risk of recurrence 18 vs. 10.5%, relative risk 1.71, 95% CI: 1.2-2.5, P = 0.006. Multivariate analysis indicated that the types of PCS [OS-ASD vs. No PCS: hazard ratio (HR) 2.57; 95% CI: 1.1-6.2, P = 0.03 and complex CHD vs. No PCS: HR 2.75; 95% CI: 1.41-5.48, P = 0.004], female gender (HR 1.55; 95% CI: 1.04-2.4, P = 0.048), and severe LV dysfunction (HR 1.36; 95% CI: 1.06-1.67, P = 0.04) were independent predictors of long-term recurrence. CONCLUSION: Radiofrequency catheter ablation of CTI-AFL after surgical correction of AHD and CHD is associated with high acute success rates. The severity of the structural alterations of the underlying heart disease and consequently the type of surgical correction correlates with higher risk for recurrence.

Impact of a chronic total occlusion in an infarct-related artery on the long-term outcome of ventricular tachycardia ablation.

INTRODUCTION: In patients with a prior myocardial infarction (MI), angiographic predictors of ventricular tachycardia (VT) recurrence after ablation are lacking. Recently, a proarrhythmic effect of a chronic total occlusion (CTO) in a coronary artery has been suggested. METHODS AND RESULTS: A total of 191 patients with prior MI were referred to our Hospital between 2010 and June 2013 for a first ablation of VT. Of these, 84 patients (44%) with stable coronary artery disease that underwent a coronary angiography during the index hospitalization were included in this study. A CTO in an infarct-related artery (IRA-CTO) was present in 47 patients (56%). Patients with and without IRA-CTO did not differ in terms of comorbidities, severity of heart failure, presentation of VT or acute outcome of ablation, that was completely successful in 93% of cases. At electroanatomic mapping, IRA-CTO was associated with greater scar and especially with greater area of border zone (34 cm(2) vs. 19 cm(2) , P = 0.001). Median follow-up was 19 months (IQR 18). At follow-up, patients with IRA-CTO had a significantly higher rate of VT recurrence (47% vs. 16%, P = 0.003). At multivariate analysis, IRA-CTO resulted to be an independent predictor of VT recurrence after ablation (HR 4.05, P = 0.004). CONCLUSIONS: IRA-CTO is an independent predictor of VT recurrence after ablation and identifies a subgroup of patients with high recurrence rate despite a successful procedure. IRA-CTO is associated with greater scars and border zone area; however, this association does not completely justify its proarrhythmic effect.

The benefit of a second burst antitachycardia sequence for fast ventricular tachycardia in patients with implantable cardioverter defibrillators.

BACKGROUND: In patients with implantable cardioverter defibrillators (ICDs), an empirical burst of antitachycardia pacing (ATP) is moderately effective in terminating fast ventricular tachycardias (FVTs). It is unknown whether, in the case of failure of a first burst, a second burst attempt increases the efficacy of the intervention, without increasing morbidity. Our aim was to evaluate the safety and efficacy of a strategy of programming successive ATP sequences for FVT episodes. METHODS: A prospective study evaluated the safety and effectiveness of programming successive ATP sequences for termination of FVT episodes (cycle lengths [CLs] 250-320 ms) treated by one ATP sequence and, in the event of failure, by successive ATP attempts or shocks. RESULTS: Over a median follow-up of 54 months, 267 FVT episodes (mean CL of 295 ± 18 ms) were detected in 35 patients. Effectiveness of the first burst ATP was 64% (65% GEE-adjusted, where GEE is generalized estimating equation) and increased significantly to 83% (75% GEE-adjusted) with the second burst ATP sequence (P = 0.01). In the remaining 17% of FVT episodes with failure of the second ATP, successive bursts and shocks were required. Multivariate analysis showed that primary prevention ICD (odds ratio [OR] 5.3, 95% confidence interval [CI] 1.9-14.5, P = 0.001), sinus rhythm (OR 4.34, 95% CI 1.4-13.4, P = 0.01), nonischemic cardiomyopathy (OR 2.36, 95% CI 1.2-4.8, P = 0.02), and longer VT CL (OR 1.32, 95% CI 1.1-1.6, P = 0.002) were independently associated with effectiveness of the first or second burst pacing sequence. CONCLUSION: The addition of a second burst pacing attempt increases the effectiveness of ATP for FVT and, therefore, reduces the need for high-energy shocks.

Multiorgan failure caused by pembrolizumab and axitinib in a woman affected by metastatic clear cell renal cell carcinoma: A case report and literature review.

RATIONALE: Treatment with a combination of immune checkpoint inhibitors (ICIs) (pembrolizumab or nivolumab) and oral Tyrosine Kinase Inhibitors (TKI) targeting angiogenesis (axitinib, cabozantinib or lenvatinib) has shown benefits in terms of efficacy and survival in metastatic renal cell carcinoma (mRCC), with a favorable toxicity profile. However, some rare and serious treatment-related adverse events can be difficult to manage. PATIENT CONCERNS: Here we report the first case of an mRCC patient who, after only 2 administrations of pembrolizumab-axitinib, experienced severe multiorgan failure (MOF) with heart failure, oliguria and acute hepatitis requiring aggressive supportive treatment in intensive care unit. DIAGNOSES: A diagnosis of severe MOF induced by pembrolizumab plus axitinib was considered. INTERVENTIONS: The patient was treated with dobutamine, levosimendan along with high-dose steroids under continuous cardiologic monitoring. OUTCOMES: After treatment, the patient had a full recovery and was discharged from the hospital. LESSONS: We reviewed all the other cases of MOF reported during treatment with combined ICI-TKI in cancer patients in order to summarize incidence, clinical manifestations and management with a specific focus on the need for prompt recognition and aggressive management under multidisciplinary care.

Improved accelerated stability of starch-chia oil fatty acid inclusion complexes formed under mild reaction conditions.

The starch inclusion complexation of sensitive compounds requires the use of conditions that minimize their degradation. This research work is aimed at investigating the effect of an alkaline complexation method employing mild reaction conditions on the physicochemical properties and accelerated stability of inclusion complexes of high amylose corn starch with omega-3 and omega-6 fatty acids. Hydrolyzed chia seed oil, rich in α-linolenic and linoleic fatty acids, was used as guest material and was incorporated at two ratios (10 and 20 % w/w hydrolysate/starch). Under the reaction conditions assessed, it were successfully formed V-type inclusion complexes with a high content of omega-3 and omega-6 (3.9-6 %). The initial hydrolysate concentration did not have a significant effect on the structural (crystallinity, short-range order) and thermal (dissociation temperature, melting enthalpy) properties. The method studied allowed the formation of complexes with an enhanced accelerated oxidative stability, compared to those formed using thermal treatment. The complexes formed using mild conditions with 20 % hydrolysate content had the highest oxidative stability, showing an omega-3 and omega-6 retention >90 % after 6 h of storage at 90 °C, an enhanced stability under thermogravimetric analysis, and flattened Rancimat curves, suggesting an appropriate preliminary behavior as potential carriers of bioactive fatty acids.

Predictive value of a comprehensive atrial assessment with cardiac magnetic resonance in non-ischemic cardiomyopathy: keep it simple.

Cardiac magnetic resonance (CMR) can provide a multi-parametric evaluation of left atrial (LA) size and function. A complete CMR-based LA assessment might improve the risk stratification of patients with non-ischemic dilated cardiomyopathy (DCM). We performed a comprehensive CMR-based evaluation of LA size and function, in order to assess the prognostic impact of specific LA parameters in DCM. Secondary analysis of a prospective registry (UHSM-CMR study, NCT02326324) including 648 consecutive patients with DCM and CMR evaluation of LA area and LA length. Of these, 456 had complete LA assessment covering reservoir, conduit and booster pump function and including LA reservoir strain evaluated with feature tracking. The heart failure (HF) endpoint included HF hospitalizations, HF death and heart transplant. The arrhythmic endpoint included ventricular arrhythmias (VA) (sustained or treated by implantable defibrillator) and sudden death (SD). At median follow-up of 23 months, 34 patients reached the HF endpoint; in a multivariable model including NYHA class and LVEF, LA length had incremental predictive value. LA length ≥ 69 mm was the best cut-off to predict HF events (adjusted HR 2.3, p = 0.03). Among the 456 patients with comprehensive LA assessment, only LA length was independently associated with the HF endpoint after adjusting for LVEF and NYHA class. By contrast, no LA parameter independently predicted the arrhythmic risk. In DCM patients, LA length is an independent predictor of HF events, showing stronger association than other more complex parameters of LA function. No atrial parameter predicts the risk of VA and SD.

Variations in the threshold's values for border zone and dense scar produce significant changes in the scar parameters obtained by ADAS-3D.

BACKGROUND: ADAS-3D software elaborates Cardiac Magnetic Resonance (CMR) images to obtain a quantitative evaluation of dense scar and border zone (BZ), including BZ channels, which can be useful for ventricular tachycardia ablation and for risk-stratification. However, most prior reports with ADAS-3D used flexible thresholds (60%±5% and 40%±5% of maximum pixel signal intensity -PSI) to define dense scar and BZ. It is unknown which is the impact of such variations of the thresholds values on the measurements obtained with ADAS-3D. OBJECTIVE: To quantify the degree of change in ADAS-3D measurements when different thresholds for dense scar and BZ are employed. METHODS: Single-center retrospective observational cohort study including 87 consecutive patients with previous myocardial infarction who underwent CMR. ADAS-3D software semi-automatically processed CMR sequences. We compared the scar measurements obtained using the 9 possible combinations of thresholds (55%/60%/65% and 35%/40%/45% of maximum PSI). RESULTS: The overall comparison between thresholds showed highly significant differences (p<0.001) in all scar parameters. Not a single patient maintained the same number of BZ channels with all the thresholds settings. A percentage difference of up to 200% in BZ channels numbers and channels mass was observed in all 36 comparisons. An absolute difference of up to 10 channels was also recorded. Of note, the highest median channel mass (obtained with the thresholds 35-65) was 59-fold higher as compared to the lowest one (obtained with the 45-55 cut-offs). CONCLUSIONS: Variations in threshold values result in statistically significant and high-magnitude changes in the quantification of scar parameters by ADAS-3D.

Impact of Cardiac Magnetic Resonance to Arrhythmic Risk Stratification in Nonischemic Cardiomyopathy.

Left ventricular ejection fraction-based arrhythmic risk stratification in nonischemic cardiomyopathy (NICM) is insufficient and has led to the failure of primary prevention implantable cardioverter defibrillator trials, mainly due to the inability of selecting patients at high risk for sudden cardiac death (SCD). Cardiac magnetic resonance offers unique opportunities for tissue characterization and has gained a central role in arrhythmic risk stratification in NICM. The presence of myocardial scar, denoted by late gadolinium enhancement, is a significant, independent, and strong predictor of ventricular arrhythmias and SCD with high negative predictive value. T1 maps and extracellular volume fraction, which are able to quantify diffuse fibrosis, hold promise as complementary tools but need confirmatory results from large studies.

Extracellular volume fraction improves risk-stratification for ventricular arrhythmias and sudden death in non-ischaemic cardiomyopathy.

AIMS: To evaluate whether cardiac magnetic resonance (CMR)-based parametric mapping and strain analysis can improve the risk-stratification for ventricular arrhythmias (VA) and sudden death (SD) in non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Secondary analysis of a prospective single-centre-registry (NCT02326324), including 703 consecutive NICM patients, 618 with extracellular volume (ECV) available. The combined primary endpoint included appropriate implantable cardioverter defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest and SD. During a median follow-up of 21 months, 14 patients (2%) experienced the primary endpoint. Native T1 was not associated with the primary endpoint. Left ventricular global longitudinal strain lost its significant association after adjustment for left ventricular ejection fraction (LVEF). Among patients with ECV available, 11 (2%) reached the primary endpoint. Mean ECV was significantly associated with the primary endpoint and the best cut-off was 30%. ECV ≥ 30% was the strongest independent predictor of the primary endpoint (hazard ratio 14.1, P = 0.01) after adjustment for late gadolinium enhancement (LGE) and LVEF. ECV ≥ 30% discriminated the arrhythmic risk among LGE+ cases and among those with LVEF ≤ 35%. A simple clinical risk-stratification model, based on LGE, LVEF ≤ 35% and ECV ≥ 30%, achieved an excellent predictive ability (Harrell's C 0.82) and reclassified the risk of 32% of the study population as compared to LVEF ≤ 35% alone. CONCLUSIONS: Comprehensive CMR evaluation in NICM showed that ECV was the only parameter with an independent and strong predictive value for VA/SD, on top of LGE and LVEF. A risk-stratification model based on LGE, LVEF ≤ 35% and ECV ≥ 30% achieved an excellent predictive ability for VA/SD. CLINICAL TRIAL REGISTRATION: UHSM CMR study (NCT02326324) https://clinicaltrials.gov/ct2/show/NCT02326324.

Prognostic impact of late gadolinium enhancement at the right ventricular insertion points in non-ischaemic dilated cardiomyopathy.

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.

Late gadolinium enhancement and the risk of ventricular arrhythmias and sudden death in NYHA class I patients with non-ischaemic cardiomyopathy.

AIM: To compare the risk of ventricular arrhythmias (VA) and sudden death (SD) between New York Heart Association (NYHA) class I and NYHA class II-III patients with non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Observational retrospective cohort study including patients with NICM who underwent cardiac magnetic resonance at two hospitals. The primary endpoint included appropriate implantable cardioverter defibrillator (ICD) therapies, sustained ventricular tachycardia, resuscitated cardiac arrest and SD. The secondary endpoint included heart failure (HF) hospitalizations, heart transplant, left ventricular assist device implant or HF death. Overall, 698 patients were included, 33% in NYHA class I. During a median follow-up of 31 months, the primary endpoint occurred in 57 patients (8%), with no differences between NYHA class I and NYHA class II-III cases (7% vs. 9%, p = 0.62). Late gadolinium enhancement (LGE) was the only independent predictor of the primary outcome both in NYHA class I and NYHA class II-III patients. LGE+ NYHA class I patients had a similar cumulative incidence of the primary endpoint as compared to LGE+ NYHA class II-III (p = 0.92) and a significantly higher risk as compared to LGE- NYHA class II-III cases (p < 0.001). The risk of the secondary endpoint was significantly higher in patients in NYHA class II-III as compared to those in NYHA class I (hazard ratio 3.2, p = 0.001). CONCLUSIONS: Patients with NICM in NYHA class I are not necessarily at low risk of VA and SD. Actually, LGE+ NYHA class I patients have a high risk. NYHA class I patients with high-risk factors, such as LGE, could benefit from primary prevention ICD at least as much as those in NYHA class II-III with the same risk factors.

Cardiac Magnetic Resonance as Risk Stratification Tool in Non-Ischemic Dilated Cardiomyopathy Referred for Implantable Cardioverter Defibrillator Therapy-State of Art and Perspectives.

Non-ischemic dilated cardiomyopathy (DCM) is a disease characterized by left ventricular dilation and systolic dysfunction. Patients with DCM are at higher risk for ventricular arrhythmias and sudden cardiac death (SCD). According to current international guidelines, left ventricular ejection fraction (LVEF) ≤ 35% represents the main indication for prophylactic implantable cardioverter defibrillator (ICD) implantation in patients with DCM. However, LVEF lacks sensitivity and specificity as a risk marker for SCD. It has been seen that the majority of patients with DCM do not actually benefit from the ICD implantation and, on the contrary, that many patients at risk of SCD are not identified as they have preserved or mildly depressed LVEF. Therefore, the use of LVEF as unique decision parameter does not maximize the benefit of ICD therapy. Multiple risk factors used in combination could likely predict SCD risk better than any single risk parameter. Several predictors have been proposed including genetic variants, electric indexes, and volumetric parameters of LV. Cardiac magnetic resonance (CMR) can improve risk stratification thanks to tissue characterization sequences such as LGE sequence, parametric mapping, and feature tracking. This review evaluates the role of CMR as a risk stratification tool in DCM patients referred for ICD.