Added Value of 3- Versus 2-Dimensional Echocardiography Left Ventricular Ejection Fraction to Predict Arrhythmic Risk in Patients With Left Ventricular Dysfunction

ObjectivesThis study sought to evaluate the potential clinical impact of using 3-dimensional echocardiography (3DE) to measure left ventricular ejection fraction (LVEF) in patients considered for implantable cardioverter-defibrillator (ICD) implantation and to assess the predictive value of 3DE LVEF for arrhythmic events.BackgroundICD therapy is currently recommended to prevent sudden cardiac death in patients with symptomatic heart failure and LVEF ≤35%, and in asymptomatic patients with ischemic heart disease and LVEF ≤30%. Two-dimensional echocardiography (2DE) is currently used to calculate LVEF. However, 3DE has been reported to be more reproducible and accurate than 2DE to measure LVEF.MethodsThe study prospectively enrolled 172 patients with LV dysfunction (71% ischemic). Both 2DE and 3DE LVEF were obtained during the same study. The outcome was the occurrence of major arrhythmic events (sudden cardiac death, aborted cardiac arrest, appropriate ICD therapy).ResultsAfter a median follow up of 56 (range 18 to 65) months, major arrhythmic events occurred in 30% of the patients. Compared with 2DE, 3DE changed the assignment above or below the LVEF thresholds for ICD implantation in 20% of patients, most of them having 2DE LVEFs within ± 10% from threshold. By cause-specific hazard model, 3DE LVEF was the only independent predictor of the occurrence of major arrhythmic events.ConclusionsLVEF by 3DE was an independent predictor of major arrhythmic events and improved arrhythmic risk prediction in patients with LV dysfunction. When compared with 2DE LVEF, 3DE measurement of LVEF may change the decision to implant an ICD in a sizable number of patients.     

Magnetic Resonance Mapping of Catheter Ablation Lesions After Post-Infarction Ventricular Tachycardia Ablation

ObjectivesThis study sought to describe cardiac magnetic resonance (CMR) characteristics of ablation lesions within post-infarction scar.BackgroundChronic ablation lesions created during radiofrequency ablation of ventricular tachycardia (VT) in the setting of prior myocardial infarction have not been described in humans.MethodsSeventeen patients (15 men, ejection fraction 25 ± 8%, 66 ± 6 years of age) with CMR imaging prior to repeat ablation procedures for VT were studied. Electroanatomic maps from first-time procedures and subsequent CMR images were merged and retrospectively compared with electroanatomic maps from repeat procedures.ResultsThe delay between the index ablation procedure and the CMR study was 30 ± 29 months. Late gadolinium–enhanced CMR revealed a confluent nonenhancing subendocardial dark core within the infarct-related scar tissue in all patients. Intracardiac thrombi were ruled out by transthoracic and intracardiac echocardiography. These core lesions matched the distribution of prior ablation lesions, and corresponded to unexcitable areas at repeat procedures.ConclusionsAblation lesions can be detected by CMR after VT ablation in post-infarction patients and have a different appearance than scar tissue. These lesions can be observed many months after an initial ablation.     

The Mitral Annular Disjunction of Mitral Valve Prolapse: Presentation and Outcome

ObjectivesThe aim of this study was to assess in patients with mitral valve prolapse (MVP) mitral annular disjunction (MAD) prevalence, phenotypic characteristics, and long-term outcomes (clinical arrhythmic events and excess mortality).BackgroundClinical knowledge regarding MAD of MVP remains limited and controversial, and its potential link with untoward outcomes is unsubstantiated.MethodsA cohort of 595 (278 women, mean age 61 ± 16 years) consecutive patients with isolated MVP, with comprehensive clinical, rhythmic, Doppler echocardiographic, and consistent MAD assessment, were examined. MAD prevalence, associated MVP phenotypes, and outcomes (survival, clinical arrhythmic events) starting at diagnostic echocardiography were analyzed. To balance important baseline differences, propensity scoring matching was conducted among patients with and those without MAD.ResultsThe presence of MAD was common (n = 186 [31%]) in patients with MVP, generally in younger patients, and was not random but was independently associated with severe myxomatous disease involving bileaflet MVP and marked leaflet redundancy (both P ≤ 0.0002). The presence of MAD was also independently associated with a larger left ventricle (P = 0.005). Age-matched cohort survival after MVP diagnosis was not worse with MAD (10-year survival 93% ± 2% for patients without MAD and 97% ± 1% for those with MAD; P = 0.40), even adjusted comprehensively for MVP characteristics (P = 0.80) and accounting for time-dependent mitral surgery (P = 0.60). During follow-up, 170 patients had clinical arrhythmic events (ventricular tachycardia, n = 159; arrhythmia ablation, n = 14; cardioverter-defibrillator implantation, n = 14; sudden cardiac death, n = 3). MAD was independently associated with higher risk for arrhythmic events (adjusted HR: 2.60; 95% CI: 1.87-3.62; P < 0.0001). The link between MAD and arrhythmic events persisted with time-dependent mitral surgery (adjusted HR: 2.54; 95% CI: 1.84-3.50; P < 0.0001), was strong under medical management (adjusted HR: 3.21; 95% CI: 2.03-5.06; P < 0.0001) but was weaker after mitral surgery (adjusted HR: 2.07; 95% CI: 1.24-3.43; P = 0.005).ConclusionsThis large cohort with MVP comprehensively characterized shows that MAD is frequent at MVP diagnosis and is strongly linked to advanced myxomatous degeneration. The presence of MAD was independently associated with long-term excess incidence of clinical arrhythmic events. However, within the first 10 years post-diagnosis, MAD was not linked to excess mortality, and although reassurance should be provided from the survival point of view, careful monitoring for arrhythmias is in order for MAD.     

Structural and Physiological Imaging to Predict the Risk of Lethal Ventricular Arrhythmias and Sudden Death

Identifying patients at risk of sudden cardiac death remains a major challenge in cardiovascular medicine. Advances in cardiovascular imaging have identified several anatomic and functional variables that can be quantified as continuous variables to predict the risk of developing lethal ventricular tachyarrhythmias in patients with depressed left ventricular (LV) systolic function. Some, such as LV mass, volume, and the dyssynchrony of contraction, can be derived from currently available echocardiographic and nuclear imaging modalities. Others require advanced cardiac imaging modalities with quantification of myocardial scar with gadolinium-enhanced cardiac magnetic resonance and myocardial sympathetic denervation using norepinephrine analogs and positron emission tomography or single-photon emission computed tomography offering the most promise. There is an immediate need to develop a sequential cost-effective approach that capitalizes on readily available clinical information complemented with advanced imaging modalities in selected patients to improve risk stratification for arrhythmic death beyond LV ejection fraction.     

Structural Cardiac Remodeling in Atrial Fibrillation

ObjectivesThis study sought to evaluate preablation computed tomography angiography (CTA) for atrial and epicardial features to predict atrial fibrillation (AF) recurrence after ablation.BackgroundStructural atrial remodeling is a process associated with occurrence or persistence of AF. Different anatomical imaging features have been proposed to influence atrial remodeling both negatively and positively as substrate for AF.MethodsPatients with nonvalvular AF underwent cardiac CTA before pulmonary vein isolation at 2 high-volume centers. Left atrial (LA) and right atrial volumes, LA wall thickness (LAWT), and epicardial adipose tissue volume and attenuation were evaluated. Additional subanalyses of electroanatomical maps were made. Follow-up was performed for at least 12 months, including subanalysis of repeated cardiac CTA studies. Interrater variability was assessed.ResultsOf 732 patients, 270 (36.9%) had AF recurrence after a mean of 7 months. CT analysis revealed larger indexed LA volume (47.3 mL/m² vs 43.6 mL/m²; P = 0.0001) and higher mean anterior (1.91 mm vs 1.65 mm; P < 0.0001) and posterior (1.61 mm vs 1.39 mm; P = 0.001) LAWT in patients with AF recurrence. Epicardial adipose tissue volume in patients with AF recurrence was higher (144.5 mm³ vs 128.5 mm³; P < 0.0001) and further progressed significantly in a subset of 85 patients after 2 years (+11.8 mm² vs −3.5 mm²; P = 0.041). Attenuation levels were lower, indicating a higher lipid component associated with AF recurrence (−69.1 HU vs −67.5 HU; P = 0.001). A total of 103 atrial voltage maps were highly predictive of AF recurrence and showed good discriminatory power for patients with low voltage >50% and LAWT (1.55 ± 0.5 mm vs 1.81 ± 0.6 mm; P = 0.032). Net reclassification improvement (NRI) showed a significant incremental benefit (NRI = 0.279; P < 0.0001) when adding LAWT to established risk models.ConclusionsAtrial wall thickness, epicardial fat volume, and attenuation are associated with AF recurrence in patients undergoing ablation therapy.     

Advanced Therapies for Ventricular Arrhythmias in Patients With Chagasic Cardiomyopathy: JACC State-of-the-Art Review

Chagas disease is caused by infection from the protozoan parasite Trypanosoma cruzi. Although it is endemic to Latin America, global migration has led to an increased incidence of Chagas in Europe, Asia, Australia, and North America. Following acute infection, up to 30% of patients will develop chronic Chagas disease, with most patients developing Chagasic cardiomyopathy. Chronic Chagas cardiomyopathy is highly arrhythmogenic, with estimated annual rates of appropriate implantable cardioverter-defibrillator therapies and electrical storm of 25% and 9.1%, respectively. Managing arrhythmias in patients with Chagasic cardiomyopathy is a major challenge for the clinical electrophysiologist, requiring intimate knowledge of cardiac anatomy, advanced training, and expertise. Endocardial-epicardial mapping and ablation strategy is needed to treat arrhythmias in this patient population, owing to the suboptimal long-term success rate of endocardial mapping and ablation alone. We also describe innovative approaches to improve acute and long-term clinical outcomes in patients with refractory ventricular arrhythmias following catheter ablation, such as bilateral cervicothoracic sympathectomy and bilateral renal denervation, among others.     

Clinical Applications of FDG-PET Scan in Arrhythmic Myocarditis

Background¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan has no recognized role in diagnosis, prognosis, and disease monitoring in patients with arrhythmic myocarditis.ObjectivesThe purpose of this study was to investigate the value of FDG-PET scan in arrhythmic myocarditis.MethodsThe authors enrolled 75 consecutive patients (age 47 ± 14 years, 65% men) undergoing FDG-PET scan for arrhythmic myocarditis. Myocarditis was diagnosed by endomyocardial biopsy (EMB) and, whenever applicable, cardiac magnetic resonance (CMR).ResultsIndications for FDG-PET scan included either contraindication to CMR (n = 50) or mismatch between CMR and EMB (n = 25). Overall, 50 patients (67%) had positive FDG-PET. Sensitivity was 75% referring to EMB, and 73% to CMR. Specificity was 67% referring to EMB, and 59% to CMR. FDG-PET accuracy was lower in the presence of borderline myocarditis, and either late (>30 days) or on-immunosuppression FDG-PET scanning. Anteroseptal distribution pattern, found in 12 of 50 (24%) patients including 7 of 7 cardiac sarcoidosis cases, was associated with greater occurrence of ventricular arrhythmias and atrioventricular blocks in 4.2 ± 1.7 years of follow-up (10 of 12 vs 7 of 38, and 7 of 12 vs 0 of 38, respectively; both P < 0.001). In 39 patients (52%), FDG-PET was repeated by 13 ± 2 months, allowing immunosuppression withdrawal after FDG uptake normalization either by first (76%) or second reassessment (24%).ConclusionsFDG-PET scan may be a clinically useful diagnostic technique in arrhythmic myocarditis, in particular when CMR is unsuitable because of irregular heartbeat or implantable cardioverter-defibrillator–related artifacts. Anteroseptal FDG distribution is associated with a worse arrhythmic outcome and should raise the suspicion of cardiac sarcoidosis. During follow-up, repeated FDG-PET allows myocarditis monitoring to guide immunosuppression withdrawal.     

Preventing Arrhythmic Death in Patients With Tetralogy of Fallot: JACC Review Topic of the Week

Patients with tetralogy of Fallot are at risk for ventricular arrhythmias and sudden cardiac death. These abnormalities are associated with pulmonary regurgitation, right ventricular enlargement, and a substrate of discrete, slowly-conducting isthmuses. Although these arrhythmic events are rare, their prediction is challenging. This review will address contemporary risk assessment and prevention strategies. Numerous variables have been proposed to predict who would benefit from an implantable cardioverter-defibrillator. Current risk stratification models combine independently associated factors into risk scores. Cardiac magnetic resonance imaging, QRS fragmentation assessment, and electrophysiology testing in selected patients may refine some of these models. Interaction between right and left ventricular function is emerging as a critical factor in our understanding of disease progression and risk assessment. Multicenter studies evaluating risk factors and risk mitigating strategies such as pulmonary valve replacement, ablative strategies, and use of implantable cardiac-defibrillators are needed moving forward.     

Right Ventricular Abnormalities on Cardiovascular Magnetic Resonance Imaging in Patients With Sarcoidosis

ObjectivesThis study aimed to determine the prevalence on cardiac magnetic resonance (CMR) of right ventricular (RV) systolic dysfunction and RV late gadolinium enhancement (LGE), their determinants, and their influences on long-term adverse outcomes in patients with sarcoidosis.BackgroundIn patients with sarcoidosis, RV abnormalities have been described on many imaging modalities. On CMR, RV abnormalities include RV systolic dysfunction quantified as an abnormal right ventricular ejection fraction (RVEF), and RV LGE.MethodsConsecutive patients with biopsy-proven sarcoidosis who underwent CMR for suspected cardiac involvement were studied. They were followed for 2 endpoints: all-cause death, and a composite arrhythmic endpoint of sudden cardiac death or significant ventricular arrhythmia.ResultsAmong 290 patients, RV systolic dysfunction (RVEF <40% in men and <45% in women) and RV LGE were present in 35 (12.1%) and 16 (5.5%), respectively. The median follow-up time was 3.2 years (interquartile range [IQR]: 1.6 to 5.7 years) for all-cause death and 3.0 years (IQR: 1.4 to 5.5 years) for the arrhythmic endpoint. On Cox proportional hazards regression multivariable analyses, only RVEF was independently associated with all-cause death (hazard ratio [HR]: 1.05 for every 1% decrease; 95% confidence interval [CI]: 1.01 to 1.09; p = 0.022) after adjustment for left ventricular EF, left ventricular LGE extent, and the presence of RV LGE. RVEF was not associated with the arrhythmic endpoint (HR: 1.01; 95% CI: 0.96 to 1.06; p = 0.67). Conversely, RV LGE was not associated with all-cause death (HR: 2.78; 95% CI: 0.36 to 21.66; p = 0.33), while it was independently associated with the arrhythmic endpoint (HR: 5.43; 95% CI: 1.25 to 23.47; p = 0.024).ConclusionsIn this study of patients with sarcoidosis, RV systolic dysfunction and RV LGE had distinct prognostic associations; RV systolic dysfunction but not RV LGE was independently associated with all-cause death, whereas RV LGE but not RV systolic dysfunction was independently associated with sudden cardiac death or significant ventricular arrhythmia. These findings may indicate distinct implications for the management of RV abnormalities in sarcoidosis.     

The Hypertrophic Cardiomyopathy Phenotype Viewed Through the Prism of Multimodality Imaging: Clinical and Etiologic Implications

Noninvasive contemporary imaging with echocardiography and cardiovascular magnetic resonance (CMR) provide comprehensive characterization of the hypertrophic cardiomyopathy (HCM) heart including precise definition of left ventricle (LV) wall thickness and reliable identification of morphologic abnormalities of the mitral valve, LV chamber, and myocardial tissue characterization with late gadolinium enhancement (LGE) (fibrosis). Imaging also contributes to identification of patients at risk for sudden death including novel high-risk features such as LV apical aneurysm and extensive LGE. Exercise (stress) echocardiography should be considered to demonstrate physiologic provocation of LV outflow gradients and to distinguish from patients with nonobstructive HCM. Multimodality imaging identifies patients who are optimal candidates for invasive septal reduction therapy and directs preoperative planning for extended myectomy and to optimize alcohol septal ablation. Contemporary imaging interwoven with current management strategies have resulted in a low HCM-related mortality rate.     

Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy

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

Cardiac Phenotypes and Markers of Adverse Outcome in Elite Athletes With Ventricular Arrhythmias

ObjectivesThis study describes the cardiac phenotypes and markers of adverse outcome in athletes with ventricular arrhythmias with no other discernable etiology than high exercise doses.BackgroundLittle is known about phenotypes and risk markers of life-threatening arrhythmic events in athletes with ventricular arrhythmia.MethodsWe compared high-performance athletes who have ventricular arrhythmia with healthy controls using clinical data and cardiac imaging. None of the patients had family history of arrhythmogenic cardiomyopathy or any other discernable etiology of ventricular arrhythmia. Right (RV) and left ventricular (LV) function was assessed by echocardiographic longitudinal strain (right ventricular free wall strain longitudinal [RVFWSL] and left ventricular global longitudinal strain [LVGLS]). Mechanical dispersion was defined as the standard deviation of time to peak strain in 16 LV segments. RV ejection fraction and presence of late gadolinium enhancement was assessed by cardiac magnetic resonance.ResultsWe included 43 athletes (45 ± 14 years of age, 16% female) with ventricular arrhythmias and 30 healthy athletes (41 ± 9 years of age, 7% female). Athletes with ventricular arrhythmias had worse RV function than healthy athletes by echocardiography (RVFWSL: ?22.9 ± 4.8% vs. ?26.6 ± 3.3%; p < 0.001) and by cardiac magnetic resonance (RV ejection fraction 48 ± 7% vs. 52 ± 6%; p = 0.04), and had more late gadolinium enhancement (24% vs. 3%; p = 0.03). Life-threatening arrhythmic events (aborted cardiac arrest, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy) had occurred in 23 (53%) athletes with ventricular arrhythmias. These had impaired LV function compared to those with less severe ventricular arrhythmias (LVGLS: -17.1 ± 3.0% vs. -18.8 ± 2.0%; p = 0.04). LV mechanical dispersion was an independent marker of life-threatening events (adjusted odds ratio: 2.2 [1.1 to 4.8] by 10 ms increments; p = 0.03).ConclusionsAthletes with ventricular arrhythmias had impaired RV function and more myocardial fibrosis compared to healthy athletes. Athletes with life-threatening arrhythmic events had additional LV contraction abnormalities. These phenotypes mimic arrhythmogenic cardiomyopathy and may potentially be induced by high doses of exercise in susceptible individuals.     

Evaluation of Multimodality LAA Leak Closure Methods Following Incomplete Occlusion: The LAA Leak Study

BackgroundIncomplete left atrial appendage (LAA) closure is an evolving topic of clinical significance and thromboembolic potential, with recent long-term studies suggesting lower cutoffs for relevant leak size.ObjectivesThe aim of this prospective observational study was to assess 3 different closure techniques for persistent peridevice leaks after incomplete LAA closure and compare their efficacy and safety outcomes.MethodsWe studied 160 patients (mean age 72 ± 9 years; 71% men) who underwent 1 of the 3 available modalities (detachable embolization coils, vascular plugs or septal occluders, and radiofrequency ablation) for residual central or eccentric leak closure. Both acute postprocedural success (closure or <1-mm leak at the end of the procedure) and closure at 1-year follow-up transesophageal echocardiography imaging were evaluated.ResultsOf 160 patients, 0.6%, 41.3%, and 58.1% had mild (1-2 mm), moderate (3-5 mm), and severe (≥5 mm) leaks, respectively. Baseline LAA closure type was 72.5% Watchman FLX, 16.3% Lariat, 5.6% surgical ligation, 1.9% AtriClip, and 1.9% Amulet. Successful closure (0- or <1-mm leak) was seen in 100% of patients in all cohorts following intervention, with overall complete closure (0-1 mm) or mild or minimal leaks (1-2 mm) on 1-year follow-up transesophageal echocardiography seen in 100% of the atrial septal occluder or vascular plug cohort, 85.9% of the coil cohort, and 83.3% of the radiofrequency ablation cohort (P < 0.001). Two patients (1.3%) experienced cardiac tamponade, and there were no deaths or other complications.ConclusionsPeridevice leaks can safely and effectively be closed using 3 different modalities depending on size and location.     

Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease

BackgroundThe “gray zone” of myocardial fibrosis (GZF) on cardiovascular magnetic resonance may be a substrate for ventricular arrhythmias (VAs).ObjectivesThe purpose of this study was to determine whether GZF predicts sudden cardiac death (SCD) and VAs (ventricular fibrillation or sustained ventricular tachycardia) in patients with coronary artery disease (CAD) and a wide range of left ventricular ejection fractions (LVEFs).MethodsIn this retrospective study of CAD patients, the presence of myocardial fibrosis on visual assessment (MF_VA) and GZF mass in patients with MF_VA were assessed in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs.ResultsAmong 979 patients (mean age [± SD]: 65.8 ± 12.3 years), 29 (2.96%) experienced SCD and 80 (8.17%) met the arrhythmic endpoint over median 5.82 years (interquartile range: 4.1 to 7.3 years). In the whole cohort, MF_VA was strongly associated with SCD (hazard ratio: 10.1; 95% confidence interval [CI]: 1.42 to 1,278.9) and the arrhythmic endpoint (hazard ratio: 28.0; 95% CI: 4.07 to 3,525.4). In competing risks analyses, associations between LVEF <35% and SCD (subdistribution hazard ratio [sHR]: 2.99; 95% CI: 1.42 to 6.31) and the arrhythmic endpoint (sHR: 4.71; 95% CI: 2.97 to 7.47) were weaker. In competing risk analyses of the MF_VA subcohort (n = 832), GZF using the 3SD method (GZF_3SD) >5.0 g was strongly associated with SCD (sHR: 10.8; 95% CI: 3.74 to 30.9) and the arrhythmic endpoint (sHR: 7.40; 95% CI: 4.29 to 12.8). Associations between LVEF <35% and SCD (sHR: 2.62; 95% CI: 1.24 to 5.52) and the arrhythmic endpoint (sHR: 4.14; 95% CI: 2.61 to 6.57) were weaker.ConclusionsIn CAD patients, MF_VA plus quantified GZF_3SD mass was more strongly associated with SCD and VAs than LVEF. In selecting patients for implantable cardioverter-defibrillators, assessment of MF_VA followed by quantification of GZF_3SD mass may be preferable to LVEF.     

CMR DENSE and the Seattle Heart Failure Model Inform Survival and Arrhythmia Risk After CRT

ObjectivesThis study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators.BackgroundThe SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function.MethodsCMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies.ResultsThe cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD ≥0.60 or SHFM-D ≥0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response (r = −0.57; p < 0.0001) than CURE-SVD with feature tracking (r = −0.28; p = 0.004).ConclusionsA combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future.     

Recurrence of Atrial Fibrillation After Catheter Ablation or Antiarrhythmic Drug Therapy in the CABANA Trial

BackgroundThe CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized 2,204 patients with atrial fibrillation (AF) to catheter ablation or drug therapy. Analysis by intention-to-treat showed a nonsignificant 14% relative reduction in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.ObjectivesThe purpose of this study was to assess recurrence of AF in the CABANA trial.MethodsThe authors prospectively studied CABANA patients using a proprietary electrocardiogram recording monitor for symptom-activated and 24-h AF auto detection. The AF recurrence endpoint was any post–90-day blanking atrial tachyarrhythmias lasting 30 s or longer. Biannual 96-h Holter monitoring was used to assess AF burden. Patients who used the CABANA monitors and provided 90-day post-blanking recordings qualified for this analysis (n = 1,240; 56% of CABANA population). Treatment comparisons were performed using a modified intention-to-treat approach.ResultsMedian age of the 1,240 patients was 68 years, 34.4% were women, and AF was paroxysmal in 43.0%. Over 60 months of follow-up, first recurrence of any symptomatic or asymptomatic AF (hazard ratio: 0.52; 95% confidence interval: 0.45 to 0.60; p < 0.001) or first symptomatic-only AF (hazard ratio: 0.49; 95% confidence interval: 0.39 to 0.61; p < 0.001) were both significantly reduced in the catheter ablation group. Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p < 0.001). These findings were not sensitive to the baseline pattern of AF.ConclusionsCatheter ablation was effective in reducing recurrence of any AF by 48% and symptomatic AF by 51% compared with drug therapy over 5 years of follow-up. Furthermore, AF burden was also significantly reduced in catheter ablation patients, regardless of their baseline AF type. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508)     

Cardiac Structural and Functional Consequences of Amyloid Deposition by Cardiac Magnetic Resonance and Echocardiography and Their Prognostic Roles

ObjectivesThis cross-sectional study aimed to describe the functional and structural cardiac abnormalities that occur across a spectrum of cardiac amyloidosis burden and to identify the strongest cardiac functional and structural prognostic predictors in amyloidosis using cardiac magnetic resonance (CMR) and echocardiography.BackgroundCardiac involvement in light chain and transthyretin amyloidosis is the main driver of prognosis and influences treatment strategies. Numerous measures of cardiac structure and function are assessed by multiple imaging modalities in amyloidosis.MethodsA total f 322 subjects (311 systemic amyloidosis and 11 transthyretin gene mutation carriers) underwent comprehensive CMR and transthoracic echocardiography. The probabilities of 11 commonly measured structural and functional cardiac parameters being abnormal with increasing cardiac amyloidosis burden were evaluated. Cardiac amyloidosis burden was quantified using CMR-derived extracellular volume. The prognostic capacities of these parameters to predict death in amyloidosis were assessed using Cox proportional hazards models.ResultsLeft ventricular mass and mitral annular plane systolic excursion by CMR along with strain and E/e’ by echocardiography have high probabilities of being abnormal at low cardiac amyloid burden. Reductions in biventricular ejection fractions and elevations in biatrial areas occur at high burdens of infiltration. The probabilities of indexed stroke volume, myocardial contraction fraction, and tricuspid annular plane systolic excursion (TAPSE) being abnormal occur more gradually with increasing extracellular volume. Ninety patients (28%) died during a median follow-up of 22 months (interquartile range: 10 to 38 months). Univariable analysis showed that all imaging markers studied significantly predicted outcome. Multivariable analysis showed that TAPSE (hazard ratio: 1.46; 95% confidence interval: 1.16 to 1.85; p < 0.01) and indexed stroke volume (hazard ratio: 1.24; 95% confidence interval: 1.04 to 1.48; p < 0.05) by CMR were the only independent predictors of mortality.ConclusionsSpecific functional and structural abnormalities characterize different burdens of cardiac amyloid deposition. In a multimodality imaging assessment of a large cohort of amyloidosis patients, CMR-derived TAPSE and indexed stroke volume are the strongest prognostic cardiac functional markers.     

Emerging Techniques for Risk Stratification in Nonischemic Dilated Cardiomyopathy: JACC Review Topic of the Week

Dilated cardiomyopathy (DCM) is a common condition, which carries significant mortality from sudden cardiac death and pump failure. Left ventricular ejection fraction has conventionally been used as a risk marker for sudden cardiac death, but has performed poorly in trials. There have been significant advances in the areas of cardiac magnetic resonance imaging and genetics, which are able to provide useful rick prediction in DCM. Biomarkers and cardiopulmonary exercise testing are well validated in the prediction of risk in heart failure; however, they have been tested less specifically in the DCM setting. This review will discuss these methods with a view toward multiparametric risk assessment in DCM with the hope of creating parametric risk models to predict sudden cardiac death and pump failure in the DCM population.     

Prognostic Value of Late Gadolinium Enhancement Detected on Cardiac Magnetic Resonance in Cardiac Sarcoidosis

BackgroundSarcoidosis is a complex multisystem inflammatory disorder, with approximately 5% of patients having overt cardiac involvement. Patients with cardiac sarcoidosis are at an increased risk of both ventricular arrhythmias and sudden cardiac death. Previous studies have shown that the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is associated with an increased risk of mortality and ventricular arrhythmias and may be useful in predicting prognosis.ObjectivesThis systematic review and meta-analysis assessed the value of LGE on CMR imaging in predicting prognosis for patients with known or suspected cardiac sarcoidosis.MethodsThe authors searched the Embase and MEDLINE databases from inception to March 2022 for studies reporting individuals with known or suspected cardiac sarcoidosis referred for CMR with LGE. Outcomes were defined as all-cause mortality, ventricular arrhythmia, or a composite outcome of either death or ventricular arrhythmias. The primary analysis evaluated these outcomes according to the presence of LGE. A secondary analysis evaluated outcomes specifically according to the presence of biventricular LGE.ResultsThirteen studies were included (1,318 participants) in the analysis, with an average participant age of 52.0 years and LGE prevalence of 13% to 70% over a follow-up of 3.1 years. Patients with LGE on CMR vs those without had higher odds of ventricular arrhythmias (odds ratio [OR]: 20.3; 95% CI: 8.1-51.0), all-cause mortality (OR: 3.45; 95% CI: 1.6-7.3), and the composite of both (OR: 9.2; 95% CI: 5.1-16.7). Right ventricular LGE is invariably accompanied by left ventricular LGE. Biventricular LGE is also associated with markedly increased odds of ventricular arrhythmias (OR: 43.6; 95% CI: 16.2-117.2).ConclusionsPatients with known or suspected cardiac sarcoidosis with LGE on CMR have significantly increased odds of both ventricular arrhythmias and all-cause mortality. The presence of biventricular LGE may confer additional prognostic information regarding arrhythmogenic risk.     

Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias

BackgroundMyocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia.ObjectivesThis study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia.MethodsA total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T.ResultsDiastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036).ConclusionsDT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor.