Evaluation of a deep learning-enabled automated computational heart modelling workflow for personalized assessment of ventricular arrhythmias.

Personalized, image-based computational heart modelling is a powerful technology that can be used to improve patient-specific arrhythmia risk stratification and ventricular tachycardia (VT) ablation targeting. However, most state-of-the-art methods still require manual interactions by expert users. The goal of this study is to evaluate the feasibility of an automated, deep learning-based workflow for reconstructing personalized computational electrophysiological heart models to guide patient-specific treatment of VT. Contrast-enhanced computed tomography (CE-CT) images with expert ventricular myocardium segmentations were acquired from 111 patients across five cohorts from three different institutions. A deep convolutional neural network (CNN) for segmenting left ventricular myocardium from CE-CT was developed, trained and evaluated. From both CNN-based and expert segmentations in a subset of patients, personalized electrophysiological heart models were reconstructed and rapid pacing was used to induce VTs. CNN-based and expert segmentations were more concordant in the middle myocardium than in the heart's base or apex. Wavefront propagation during pacing was similar between CNN-based and original heart models. Between most sets of heart models, VT inducibility was the same, the number of induced VTs was strongly correlated, and VT circuits co-localized. Our results demonstrate that personalized computational heart models reconstructed from deep learning-based segmentations even with a small training set size can predict similar VT inducibility and circuit locations as those from expertly-derived heart models. Hence, a user-independent, automated framework for simulating arrhythmias in personalized heart models could feasibly be used in clinical settings to aid VT risk stratification and guide VT ablation therapy. KEY POINTS: Personalized electrophysiological heart modelling can aid in patient-specific ventricular tachycardia (VT) risk stratification and VT ablation targeting. Current state-of-the-art, image-based heart models for VT prediction require expert-dependent, manual interactions that may not be accessible across clinical settings. In this study, we develop an automated, deep learning-based workflow for reconstructing personalized heart models capable of simulating arrhythmias and compare its predictions with that of expert-generated heart models. The number and location of VTs was similar between heart models generated from the deep learning-based workflow and expert-generated heart models. These results demonstrate the feasibility of using an automated computational heart modelling workflow to aid in VT therapeutics and has implications for generalizing personalized computational heart technology to a broad range of clinical centres.

Safety and efficacy of cryoballoon versus radiofrequency ablation for atrial fibrillation in elderly patients: A real-world evidence.

BACKGROUND: There are limited data describing the experience of radiofrequency (RF) vs. cryoballoon (CB) ablation for atrial fibrillation (AF) among elderly patients in the United States. METHODS: We conducted a retrospective analysis of patients ≥75 years of age undergoing index RF vs. CB ablation between January 2014 and May 2020 at our center. The choice of ablation technique was left to the operator's discretion. Major complications and efficacy, defined as freedom from any atrial tachyarrhythmia (ATA) lasting ≥30 s after one year of follow-up, were assessed in patients with index RF vs. CB ablation. RESULTS: In our cohort of 186 patients, the median age was 78 (76-81) years, 54.8% were men, and 39.2% had persistent AF. The median CHA2DS2-VASc score was 4 (3-4), while the median duration of AF was 3 (1-7) years. The majority (n = 112, 60.2%) underwent RF ablation. The median procedure time was significantly lower in CB group (197 vs 226.5 min, p=<0.01). The incidence of complications was similar in the two sub-groups (RF: 1.8% vs. CB: 2.7%, p = 0.67). Similarly, arrhythmia-free survival rate on antiarrhythmic drugs at 1-year follow-up remained statistically comparable (63.4% vs. 68.9%, p = 0.33) between patients receiving RF vs. CB ablation. CONCLUSION: The safety and efficacy of RF vs. CB ablation for AF remained comparable in our cohort of patients older than 75 years. CB ablation was associated with a shorter procedure time.

Transition from transesophageal echocardiography to cardiac computed tomography for the evaluation of left atrial appendage thrombus prior to atrial fibrillation ablation and incidence of cerebrovascular events during the COVID-19 pandemic.

BACKGROUND: Transesophageal echocardiography (TEE) is variably performed before atrial fibrillation (AF) ablation to evaluate left atrial appendage (LAA) thrombus. We describe our experience with transitioning to the pre-ablation cardiac computed tomography (CT) approach for the assessment of LAA thrombus during the COVID-19 pandemic. METHODS: We studied consecutive patients undergoing AF ablation at our center. The study cohort was divided into pre- versus post-COVID groups. The pre-COVID cohort included ablations performed during the 1 year before the COVID-19 pandemic; pre-ablation TEE was used routinely to evaluate LAA thrombus in high-risk patients. Post-COVID cohort included ablations performed during the 1 year after the COVID-19 pandemic; pre-ablation CT was performed in all patients, with TEE performed only in patients with LAA thrombus by CT imaging. The demographics, clinical history, imaging, and ablation characteristics, and peri-procedural cerebrovascular events (CVEs) were recorded. RESULTS: A total of 637 patients (pre-COVID n = 424, post-COVID n = 213) were studied. The mean age was 65.6 ± 10.1 years in the total cohort, and the majority were men. There was a significant increase in pre-ablation CT imaging from pre- to post-COVID cohort (74.8% vs. 93.9%, p ≤ .01), with a significant reduction in TEEs (34.6% vs. 3.7%, p ≤ .01). One patient in the post-COVID cohort developed CVE following negative pre-ablation CT. However, the incidence of peri-procedural CVE between both cohorts remained statistically unchanged (0% vs. 0.4%, p = .33). CONCLUSION: Implementation of pre-ablation CT-only imaging strategy with selective use of TEE for LAA thrombus evaluation is not associated with increased CVE risk during the COVID-19 pandemic.

Ablation outcomes for atypical atrial flutter versus recurrent atrial fibrillation following index pulmonary vein isolation.

BACKGROUND: Data related to electrophysiologic characteristics of atypical atrial flutter (AFL) following atrial fibrillation (AF) ablation and its prognostic value on repeat ablation success are limited. METHODS: We studied consecutive patients who underwent a repeat left atrial (LA) ablation procedure for either recurrent AF or atypical AFL, at least 3 months after index AF ablation, between January 2012 and July 2019. The demographics, clinical history, procedural data, complications, and 1-year arrhythmia-free survival rates were recorded for each subject after the first repeat ablation. RESULTS: A total of 336 patients were included in our study. Among these 336 patients, 102 underwent a repeat ablation procedure for atypical AFL and 234 underwent a repeat ablation procedure for recurrent AF. The mean age was 63.7 ± 10.7 years, and 72.6% of patients were men. The atypical AFL cohort had significantly higher LA diameters (4.6 vs. 4.4 cm, p = .04) and LA volume indices (LAVi; 85.1 vs. 75.4 ml/m2 , p = .03) compared to AF patients at repeat ablation. Atypical AFL patients were more likely to have had index radiofrequency (RF) ablation (as opposed to cryoballoon) than recurrent AF patients (98% vs. 81%, p = .01). Atypical AFLs were roof-dependent in 35.6% and peri-mitral in 23.8% of cases. Major complications at repeat ablation occurred in 0.9% of the total cohort. Arrhythmia-free survival at one year was significantly higher in the recurrent atypical AFL compared to the recurrent AF cohort (75.5 vs. 65.0%, p = .04). CONCLUSION: In our series, roof-dependent flutter is the most common form of atypical atrial flutter post AF ablation. Patients developing atypical AFL after index AF ablation have greater LA dimensions than patients with recurrent AF. The success rate of first repeat ablation is significantly higher among patients with recurrent atypical AFL as compared to recurrent AF after index AF ablation.

Efficacy of catheter ablation for premature ventricular contractions in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Premature ventricular contractions (PVCs) may be found in any stage of arrhythmogenic right ventricular cardiomyopathy (ARVC) and have been associated with the risk of sustained ventricular tachycardia (VT). OBJECTIVE: To investigate the role of PVC ablation in ARVC patients. METHODS: We studied consecutive ARVC patients who underwent PVC ablation due to symptomatic high PVC burden. Mean daily PVC burden and antiarrhythmic drug (AAD) use were assessed before and after the procedure. Complete long-term success was defined as more than 80% reduction in PVC burden off of membrane-active AADs. RESULTS: Eight patients (37 ± 15 years; 4 males) underwent PVC ablation. The mean daily PVC burden before ablation ranged from 5.4% to 24.8%. A total of 7 (87.5%) patients underwent epicardial ablation. Complete acute elimination of PVCs was achieved in 4 (50%) patients (no complications). The mean daily PVC burden variation ranged from an 87% reduction to a 26% increase after the procedure. Over a median follow-up of 345 days (range: 182-3004 days), only one (12.5%) patient presented complete long-term success, and 6 (75%) patients either maintained or increased the need for Class I or Class III AADs. A total of 2 (25%) patients experienced sustained VT for the first time following the ablation procedure, requiring repeat ablation. No death or heart transplantation occurred. CONCLUSION: PVC ablation was not associated with a consistent reduction of the PVC burden in ARVC patients with symptomatic, frequent PVCs. PVC ablation may be reserved for highly symptomatic patients who failed AADs. Additional investigation is required to improve the efficacy of PVC ablation in ARVC patients.

Repeat catheter ablation for recurrent atrial fibrillation: Electrophysiologic findings and clinical outcomes.

INTRODUCTION: Atrial fibrillation (AF) ablation is successful in 60%-80% of optimal candidates, with many patients requiring repeat procedures. We performed a detailed examination of electrophysiologic findings and clinical outcomes associated with first repeat AF ablations in the era of contact force-sensing radiofrequency (RF) catheters. METHODS: We retrospectively studied patients who underwent their first repeat AF ablations for symptomatic, recurrent AF at our center between 2013 and 2019. All repeat ablations were performed using contact force-sensing RF catheters. Pulmonary vein (PV) reconnections at repeat ablation and freedom from atrial arrhythmia 1 year after repeat ablation were evaluated. We further assessed these findings based on AF classification at the time of presentation for repeat ablation, index RF versus cryoballoon (CB) ablation, and duration (≥3 versus <3 years) between index and repeat procedures. RESULTS: Among 300 patients, there were 136 (45.3%) who presented for their first repeat ablations in persistent AF. During repeat ablation, at least one PV reconnection was found in 257 (85.6%) patients, while 159 (53%) had three to four reconnections. There was a similar distribution of reconnections among patients with persistent versus paroxysmal AF (mean: 2.7 ± 1.3 vs. 2.9 ± 1.2; p = .341), index RF versus CB ablation (mean: 2.8 ± 1.3 vs. 2.9 ± 1.2; p = .553), and ≥3 versus <3 years between index and repeat procedures (mean: 3.0 ± 1.1 vs. 2.7 ± 1.3; p = .119). At repeat ablation, the PVs were re-isolated in all patients, and additional non-PV ablation was performed in 171 (57%) patients. Freedom from atrial arrhythmia at 1-year follow-up after repeat ablation was 66%, similar among those with persistent versus paroxysmal AF (65.4% vs. 66.5%; p = .720), index RF versus CB ablation (66.7% vs. 68.9%; p = .930), and ≥3 versus <3 years between index and repeat ablations (64.4% vs. 66.7%; p = .760). Major complications occurred in a total of 4 (1.3%) patients. CONCLUSION: In a contemporary cohort of patients receiving their first repeat AF ablations using contact force-sensing RF catheters, PV reconnections were common, and freedom from atrial arrhythmia was 66% at 1-year follow-up. The distributions of PV reconnections and rates of freedom from atrial arrhythmia were similar, based on persistent versus paroxysmal AF at presentation for repeat ablation, index RF versus CB ablation, and duration between index and repeat procedures. The incidence of major complications was very low.

Spatial dispersion analysis of LGE-CMR for prediction of ventricular arrhythmias in patients with cardiac sarcoidosis.

BACKGROUND: Patients with cardiac sarcoidosis (CS) are at increased risk of life-threatening ventricular arrhythmias (VA). Current approaches to risk stratification have limited predictive value. OBJECTIVES: To assess the utility of spatial dispersion analysis of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), as a quantitative measure of myocardial tissue heterogeneity, in risk stratifying patients with CS for VA and death. METHODS: Sixty two patients with CS underwent LGE-CMR. LGE images were segmented and dispersion maps of the left and right ventricles were generated as follows. Based on signal intensity (SI), each pixel was categorized as abnormal (SI ≥3SD above the mean), intermediate (SI 1-3 SD above the mean) or normal (SI <1SD above the mean); and each pixel was then assigned a value of 0 to 8 based on the number of adjacent pixels of a different category. Average dispersion score was calculated for each patient. The primary endpoint was VA during follow up. The composite of VA or death was assessed as a secondary endpoint. RESULTS: During 4.7 ± 3.5 years of follow up, six patients had VA, and five without documented VA died. Average dispersion score was significantly higher in patients with VA versus those without (0.87 ± 0.08 vs. 0.71 ± 0.16; p = .002) and in patients with events versus those without (0.83 ± 0.08 vs. 0.70 ± 0.16; p = .003). Patients at higher tertiles of dispersion score had a higher incidence of VA (p = .03) and the composite of VA or death (p = .01). CONCLUSIONS: Increased substrate heterogeneity, quantified by spatial dispersion analysis of LGE-CMR, may be helpful in risk-stratifying patients with CS for adverse events, including life-threatening arrhythmias.

Extended use of the wearable cardioverter-defibrillator in patients at risk for sudden cardiac death.

Aims: Data on outcomes in patients using the wearable cardioverter-defibrillator (WCD) > 90 days are limited. We aimed to analyse the clinical course of patients with WCD use ≤90 days vs. WCD use >90 days. Methods and results: We assessed arrhythmia events during WCD use, and ejection fraction (EF) improvement/implantable cardioverter-defibrillator (ICD) implantation at the end of WCD use in patients with WCD use ≤90 days vs. WCD use >90 days enrolled in the WEARIT-II registry, further assessed by disease aetiology (ischaemic vs. non-ischaemic vs. congenital/inherited heart disease). There were 981 (49%) patients with WCD use >90 days, and 1019 patients with WCD use ≤90 days (median 120 vs. 55 days). There was a lower incidence of sustained ventricular tachycardia/ventricular fibrillation (VT/VF) events (11 vs. 50 events per 100 patient-years, P < 0.001), WCD treated VT/VF events (1 vs. 8 events per 100 patient-years, P < 0.001), and non-sustained VT events (21 vs. 51 events per 100 patient-years, P = 0.008) with WCD use >90 vs. WCD use ≤90 days. Non-ischaemic cardiomyopathy patients presented with similar rates of sustained VT/VF events during WCD use >90 vs. ≤90 days (13.4 vs. 13.7 events per 100 patient-years, P = 0.314), while most of these events terminated spontaneously. One-third of the patients with extended WCD use further improved their EF and they were not implanted with an ICD, with similar rates among ischaemic and non-ischaemic patients. Conclusions: In WEARIT-II, patients with extended WCD use >90 days remain at risk for ventricular arrhythmia events. One-third of the patients with WCD use >90 days further improved their EF, avoiding the need to consider ICD implantation.

Clinical aspects of the three major genetic forms of long QT syndrome (LQT1, LQT2, LQT3).

BACKGROUND: A comprehensive report on the clinical course of the three major genotypes of the long QT syndrome (LQTS) in a large U.S. patient cohort is lacking. METHODS: Our study consisted of 1,923 U.S. subjects from the Rochester-based LQTS Registry with genotype-positive LQT1 (n = 879), LQT2 (n = 807), and LQT3 (n = 237). We evaluated the risk of a first cardiac event (syncope, aborted cardiac arrest, or sudden cardiac death, whichever occurred first) from birth through age 50 years. Cox proportional hazards regression models incorporating clinical covariates were used to assess genotype-specific risk of cardiac events. RESULTS: For all three genotypes, the cumulative probability of a first cardiac event increased most markedly during adolescence. Multivariate analysis identified proband status and QTc > 500 ms as predictors of cardiac events in all three genotypes, and males <14 years and females >14 years as predictors of cardiac events in LQT1 and LQT2 only. Beta-blockers significantly reduced the risk of cardiac events in LQT1 (HR: 0.49, p = .002) and LQT2 patients (HR: 0.48, p = .001). A trend toward beta-blocker benefit in reducing cardiac events was found in LQT3 females (HR: 0.32, p = .078), but not in LQT3 males (HR: 1.37, p = .611). CONCLUSION: Risk factors and outcomes in LQTS patients varied by genotype. In all three genotypes, proband status and prolonged QTc were risk factors for cardiac events. Younger males and older females experienced increased risk in LQT1 and LQT2 only. Beta-blockers were most effective in reducing cardiac events in LQT1 and LQT2, with a potential benefit in LQT3 females.

Effect of Significant Weight Change on Inappropriate Implantable Cardioverter-Defibrillator Therapy.

BACKGROUND: Weight loss has been associated with adverse outcomes among heart failure (HF) patients, including those receiving cardiac resynchronization therapy with defibrillator (CRT-D). The effect of significant weight change on inappropriate implantable cardioverter-defibrillator (ICD) therapy among CRT-D patients is not well understood. METHODS: We evaluated the impact of significant weight change at 1 year on subsequent inappropriate ICD therapy during follow-up among 993 CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. Patients were divided into three subgroups based on weight change at 1 year after enrollment: weight loss (weight loss ≥ 5%), weight gain (weight gain ≥ 5%), and stable weight (weight loss and weight gain < 5%). The primary end point was inappropriate ICD therapy. Secondary end point included inappropriate ICD therapy related to supraventricular arrhythmias (SVAs). RESULTS: There were 102 (10.3%) patients who experienced weight loss, 689 (69.4%) whose weight was stable, and 202 (20.3%) who gained weight at 1 year. Patients with weight loss had increased risk of subsequent inappropriate ICD therapy relative to patients with stable weight (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.39-3.98, P = 0.001) or weight gain (HR = 2.27, 95% CI: 1.18-4.38, P = 0.014). Furthermore, patients losing weight were at greater risk of subsequent inappropriate ICD therapy related to SVAs when compared to patients with stable weight (HR = 2.16, 95% CI: 1.18-3.95, P = 0.013) or weight gain (HR = 2.02, 95% CI: 0.95-4.29, P = 0.068). CONCLUSION: In mild HF patients receiving CRT-D, significant weight loss at 1 year is associated with increased risk of subsequent inappropriate ICD therapy, including risk related to SVAs.

Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a MADIT-RIT substudy.

BACKGROUND: The effects of heart failure (HF) severity on risk of inappropriate implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly investigated. We aimed to study the association between HF severity and inappropriate ICD therapy in MADIT-RIT. METHODS: MADIT-RIT randomized 1,500 patients to three ICD programming arms: conventional (Arm A), high-rate cut-off (Arm B: ≥200 beats/min), and delayed therapy (Arm C: 60-second delay for ≥170 beats/min). We evaluated the association between New York Heart Association (NYHA) class III (n = 256) versus class I-II (n = 251) and inappropriate ICD therapy in Arm A patients with ICD-only and cardiac resynchronization therapy with defibrillator (CRT-D). We additionally assessed benefit of novel ICD programming in Arms B and C versus Arm A by NYHA classification. RESULTS: In Arm A, the risk of inappropriate therapy was significantly higher in those with NYHA III versus NYHA I-II for both ICD (hazard ratio [HR] = 2.55, confidence interval [CI]: 1.51-4.30, P < 0.001) and CRT-D patients (HR = 3.73, CI: 1.14-12.23, P = 0.030). This was consistent for inappropriate ATP and inappropriate ICD therapy < 200 beats/min, but not for inappropriate shocks. Novel ICD programming significantly reduced inappropriate therapy in patients with both NYHA III (Arm B vs Arm A: HR = 0.08, P < 0.001; Arm C vs Arm A: HR = 0.17, P < 0.001) and NYHA I-II (Arm B vs Arm A: HR = 0.25, P < 0.001; Arm C vs Arm A: HR = 0.28, P < 0.001). CONCLUSION: Patients with more severe HF are at increased risk for inappropriate ICD therapy, particularly ATP due to arrhythmias < 200 beats/min. Novel programming with high-rate cut-off or delayed detection reduces inappropriate ICD therapies in both mild and moderate HF.

Effect of cardiac resynchronization therapy on the risk of ventricular tachyarrhythmias in patients with chronic kidney disease.

BACKGROUND: The effect of chronic kidney disease (CKD) on benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in reducing ventricular tachyarrhythmia (VTA) risk among mild heart failure (HF) patients is not well understood. METHODS: We evaluated the impact of baseline renal function on VTAs in 1274 left bundle branch block (LBBB) patients enrolled in MADIT-CRT. Two prespecified subgroups were created based on estimated glomerular filtration rate (GFR): GFR <60 (n = 413) and GFR ≥60 ml/min/1.73 m2 (n = 861). Primary end point was ventricular tachycardia/ventricular fibrillation/death (VT/VF/death). Secondary end points were any VT/VF and ventricular tachycardia ≥ 200 bpm or VF (fast VT/VF). RESULTS: There were 413 (32%) LBBB patients presenting with CKD, primarily of moderate severity (GFR mean 48.1 ± 8.3). For patients with and without CKD, CRT-D was associated with lower risk of the primary end point (GFR<60: HR = 0.61, 95% CI: 0.41-0.89, p = .010; GFR≥60: HR = 0.58, 95% CI: 0.52-0.89, p = .005), relative to ICD-only treatment. For patients in both renal function categories, CRT-D in comparison to ICD alone was associated with lower risk of VT/VF (GFR<60: HR = 0.68, 95% CI: 0.42-1.10, p = .113; GFR≥60: HR = 0.65, 95% CI: 0.48-0.88, p = .005) and fast VT/VF (GFR<60: HR = 0.49, 95% CI: 0.25-0.96, p = .038; GFR≥60: HR = 0.55, 95% CI: 0.39-0.80, p = .001), when accounting for competing mortality risk. This effect was independent of CRT-induced reverse remodeling. CONCLUSION: Among mild HF patients with LBBB, those with and without CKD both derived benefit from CRT-D in risk reduction in VTAs, independent of cardiac reverse remodeling.

Acute renal failure is associated with higher death and disability in patients with acute ischemic stroke: analysis of nationwide inpatient sample.

BACKGROUND AND PURPOSE: Acute renal failure (ARF) in setting of acute ischemic stroke (AIS) is associated with worse outcome. We sought to determine the prevalence of ARF and effect on outcomes of patients with AIS. METHODS: Data from all patients admitted to US hospitals between 2002 and 2010 with a primary discharge diagnosis of ischemic stroke and secondary diagnosis of ARF were included. The effect of ARF on rates of intracerebral hemorrhage and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis. RESULTS: Of 7,068,334 patients with AIS, 372,223 (5.3%) had ARF during hospitalization. Dialysis was required in 2364 (0.6%) of 372,223 patients. Patients with AIS with ARF had higher rates of moderate to severe disability (41.3% versus 30%; P<0.0001), intracerebral hemorrhage (1.0% versus 0.5%; P<0.0001), and in-hospital mortality (8.4% versus 2.9%; P<0.0001) compared with those without ARF. After adjusting for confounding factors, patients with AIS with ARF had higher odds of moderate to severe disability (odds ratio, 1.3; 95% confidence interval, 1.3-1.4; P<0.0001), intracerebral hemorrhage (odds ratio, 1.4; 95% confidence interval, 1.3-1.6; P<0.0001), and death (odds ratio, 2.2; 95% confidence interval, 2.0-2.2; P<0.0001). CONCLUSIONS: ARF in patients with AIS is associated with significantly higher rates of moderate to severe disability at discharge and in-hospital mortality.

Association of epicardial and intramyocardial fat with ventricular arrhythmias.

BACKGROUND: Among patients with ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM), myocardial fibrosis is associated with an increased risk for ventricular arrhythmia (VA). Growing evidence suggests that myocardial fat contributes to ventricular arrhythmogenesis. However, little is known about the volume and distribution of epicardial adipose tissue and intramyocardial fat and their relationship with VAs. OBJECTIVE: The purpose of this study was to assess the association of contrast-enhanced computed tomography (CE-CT)-derived left ventricular (LV) tissue heterogeneity, epicardial adipose tissue volume, and intramyocardial fat volume with the risk of VA in ICM and NICM patients. METHODS: Patients enrolled in the PROSE-ICD registry who underwent CE-CT were included. Intramyocardial fat volume (voxels between -180 and -5 Hounsfield units [HU]), epicardial adipose tissue volume (between -200 and -50 HU), and LV tissue heterogeneity were calculated. The primary endpoint was appropriate ICD shocks or sudden arrhythmic death. RESULTS: Among 98 patients (47 ICM, 51 NICM), LV tissue heterogeneity was associated with VA (odds ratio [OR] 1.10; P = .01), particularly in the ICM cohort. In the NICM subgroup, epicardial adipose tissue and intramyocardial fat volume were associated with VA (OR 1.11, P = .01; and OR = 1.21, P = .01, respectively) but not in the ICM patients (OR 0.92, P =.22; and OR = 0.96, P =.19, respectively). CONCLUSION: In ICM patients, increased fat distribution heterogeneity is associated with VA. In NICM patients, an increased volume of intramyocardial fat and epicardial adipose tissue is associated with a higher risk for VA. Our findings suggest that fat's contribution to VAs depends on the underlying substrate.

Association of left ventricular tissue heterogeneity and intramyocardial fat on computed tomography with ventricular arrhythmias in ischemic cardiomyopathy.

Background: Gray zone, a measure of tissue heterogeneity on late gadolinium enhanced-cardiac magnetic resonance (LGE-CMR) imaging, has been shown to predict ventricular arrhythmias (VAs) in ischemic cardiomyopathy (ICM) patients. However, no studies have described whether left ventricular (LV) tissue heterogeneity and intramyocardial fat mass on contrast-enhanced computed tomography (CE-CT), which provides greater spatial resolution, is useful for assessing the risk of VAs in ICM patients with LV systolic dysfunction and no previous VAs. Objective: The purpose of this proof-of-concept study was to determine the feasibility of measuring global LV tissue heterogeneity and intramyocardial fat mass by CE-CT for predicting the risk of VAs in ICM patients with LV systolic dysfunction and no previous history of VAs. Methods: Patients with left ventricular ejection fraction ≤35% and no previous VAs were enrolled in a prospective, observational registry and underwent LGE-CMR. From this cohort, patients with ICM who additionally received CE-CT were included in the present analysis. Gray zone on LGE-CMR was defined as myocardium with signal intensity (SI) > peak SI of healthy myocardium but <50% maximal SI. Tissue heterogeneity on CE-CT was defined as the standard deviation of the Hounsfield unit image gradients (HU/mm) within the myocardium. Intramyocardial fat on CE-CT was identified as regions of image pixels between -180 and -5 HU. The primary outcome was VAs, defined as appropriate implantable cardioverter-defibrillator shock or sudden arrhythmic death. Results: The study consisted of 47 ICM patients, 13 (27.7%) of whom experienced VA events during mean follow-up of 5.6 ± 3.4 years. Increasing tissue heterogeneity (per HU/mm) was significantly associated with VAs after multivariable adjustment, including for gray zone (odds ratio [OR] 1.22; P = .019). Consistently, patients with tissue heterogeneity values greater than or equal to the median (≥22.2 HU/mm) had >13-fold significantly increased risk of VA events, relative to patients with values lower than the median, after multivariable adjustment that included gray zone (OR 13.13; P = .028). The addition of tissue heterogeneity to gray zone improved prediction of VAs (area under receiver operating characteristic curve increased from 0.815 to 0.876). No association was found between intramyocardial fat mass on CE-CT and VAs (OR 1.00; P = .989). Conclusion: In ICM patients, CE-CT-derived LV tissue heterogeneity was independently associated with VAs and may represent a novel marker useful for risk stratification.

Indications for Left Atrial Appendage Occlusion in the United States and Associated In-Hospital Outcomes: Results From the NCDR LAAO Registry.

BACKGROUND: The Food and Drug Administration approved left atrial appendage occlusion with the Watchman device for patients who are at increased stroke risk and are suitable for oral anticoagulation but who have an appropriate reason to seek a nondrug alternative. These broad criteria raise the question of their interpretation in clinical practice. There is a lack of studies comprehensively evaluating the indications for Watchman implantation among a large series of patients from contemporary, real-world practice in the United States. METHODS: We used the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry to identify Watchman procedures performed between 2016 and 2018. We assessed procedural indications for Watchman implantation in the United States and evaluated the association between procedural indications and in-hospital adverse events. RESULTS: A total of 38 314 procedures were included. The mean patient age was 76.1±8.1 years, and 58.9% were men. The mean CHA2DS2-VASc score was 4.8±1.5, whereas the mean hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) score was 3.0±1.1. Prior stroke or transient ischemic attack was reported in 40.2% and prior bleeding in 70.1%, with gastrointestinal bleeding being most common (41.9%). The most common site-reported procedural indications for Watchman implantation were increased thromboembolic risk (64.8%) and history of major bleed (64.3%), followed by high fall risk (35.5%). Most (71.9%) had ≥2 procedural indications. Patients with high fall risk had increased risk of in-hospital adverse events (adjusted OR, 1.12; P=0.025), but no other differences were found in the risk of in-hospital adverse events by procedural indication. CONCLUSIONS: Among patients in the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry, the most common procedural indications for Watchman implantation were increased thromboembolic risk, history of major bleed, and high fall risk. A majority of patients had multiple procedural indications. High fall risk conferred a modestly increased risk of in-hospital adverse events.

Antithrombotic Therapy After Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

BACKGROUND: Pivotal trials of percutaneous left atrial appendage occlusion (LAAO) used specific postprocedure treatment protocols. OBJECTIVES: This study sought to evaluate patterns of postprocedure care after LAAO with the Watchman device in clinical practice and compare the risk of adverse events for different discharge antithrombotic strategies. METHODS: We evaluated patients in the LAAO Registry of the National Cardiovascular Data Registry who underwent LAAO with the Watchman device between 2016 and 2018. We assessed adherence to the full postprocedure trial protocol including standardized follow-up, imaging, and antithrombotic agents and then evaluated the most commonly used antithrombotic strategies and compared the rates and risk of adverse events at 45 days and 6 months by means of multivariable COX frailty regression. RESULTS: Among 31,994 patients undergoing successful LAAO, only 12.2% received the full postprocedure treatment protocol studied in pivotal trials; the most common protocol deviations were with discharge antithrombotic medications. The most common discharge medication strategies were warfarin and aspirin (36.9%), direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin only (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (5.0%). In multivariable Cox frailty regression, the adjusted risk of any adverse event through the 45-day follow-up visit were significantly lower for discharge on warfarin alone (HR: 0.692; 95% CI: 0.569-0.841) and DOAC alone (HR: 0.731; 95% CI: 0.574-0.930) compared with warfarin and aspirin. Warfarin alone retained lower risk at the 6-month follow-up. CONCLUSIONS: In contemporary U.S. practice, practitioners rarely used the full U.S. Food and Drug Administration-approved postprocedure treatment protocols studied in pivotal trials of the Watchman device. Discharge after implantation on warfarin or DOAC without concomitant aspirin was associated with lower risk of adverse outcomes.

Longitudinal Outcomes Associated With Non-Evidence-Based Implantable Cardioverter-Defibrillators Among Medicare Beneficiaries (From the National Cardiovascular Data Registry).

Primary prevention implantable cardioverter-defibrillators (ICDs) in patients with recent myocardial infarction or coronary revascularization and those with newly diagnosed or severe heart failure (HF) are considered non-evidence-based, as defined by pivotal randomized clinical trials. Although non-evidence-based ICDs have been associated previously with greater risk of in-hospital adverse events, longitudinal outcomes are not known. We used Medicare-linked data from the National Cardiovascular Data Registry's ICD Registry to identify patients discharged alive following first-time primary prevention ICD implantations performed between 2010 and 2013. We compared longitudinal outcomes, including all-cause mortality and all-cause hospital readmission among patients receiving non-evidence-based versus evidence-based ICDs, up to 4.75 years after implantation, using multivariable time-to-event analyses. Of 71,666 ICD implantations, 9,609 (13.4%) were classified as non-evidence-based. Compared to patients receiving evidence-based ICDs, non-evidence-based ICD recipients had greater mortality risk at 90 days (HR = 1.44, CI: 1.37 - 1.52, p <0.0001) and at 1 year (HR = 1.19, CI: 1.15 - 1.24, p <0.0001), but similar mortality risk at 3 years (HR = 1.03, CI: 0.98 - 1.08, p = 0.2630). Risk of all-cause hospitalization was higher in patients with non-evidence-based ICDs at 90 days (HR = 1.17, CI: 1.14 - 1.20, p <0.0001), but the difference diminished at 1 year (HR = 1.04, CI 1.00 - 1.07, p = 0.0272) and at 3 years (HR = 0.94, CI: 0.90 - 0.99, p = 0.0105). In conclusion, among patients undergoing primary prevention ICD implantations between 2010 and 2013, those with non-evidence-based ICDs were at increased risk of mortality and readmission during longitudinal follow-up. Differences in the risk of mortality and hospitalization were highest in the first year following device implantation.

Effects of High-Flow Transesophageal Dry Air on Core Temperature: A Novel Method of Therapeutic Hypothermia.

Therapeutic hypothermia (TH) is one of the few proven neuroprotective modalities in clinical practice. However, current methods to achieve TH are suboptimal. We investigated a novel esophageal device that utilizes high-flow transesophageal dry air to achieve TH via evaporating cooling. Seven Yorkshire pigs (n = 7) underwent hypothermia therapy using a novel esophageal device that compartmentalizes a segment of esophagus through which high-flow dry air freely circulates in and out of the esophagus. Efficacy (primary objective) and safety (secondary objective) were evaluated in all animals. Safety assessment was divided into two sequential phases: (1) acute safety assessment (n = 5; terminal studies) to evaluate adverse events occurring during therapy, and (2) chronic safety assessment (n = 2; survival studies) to evaluate adverse events associated with therapy within 1 week of follow-up. After 1 hour of esophageal cooling (mean airflow rate = 64.2 ± 3.5 L/min), a significant reduction in rectal temperature was observed (37.3 ± 0.2°C → 36.3 ± 0.4°C, p = 0.002). The mean rectal temperature reduction was 1 ± 0.4°C. In none of the seven animals was oral or pharyngeal mucosa injury identified at postprocedural visual examination. In the two animals that survived, no reduction of food ingestion, signs of swallowing dysfunction or discomfort, or evidence of gastrointestinal bleeding was observed during the 1-week follow-up period. Open-chest visual inspection in those two animals did not show damage to the esophageal mucosa or surrounding structures. A novel esophageal device, utilizing high-flow transesophageal dry air, was able to efficiently induce hypothermia despite external heating. Therapy was well-tolerated, and no acute or chronic complications were found.