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Registration between phases in 4D cardiac MRI is essential for reconstructing high-quality images and appreciating the dynamics. Complex motion and limited image quality make it challenging to design regularization functionals. We propose to introduce a motion representation model (MRM) into a registration network to impose customized, site-specific, and spatially variant prior for cardiac motion.We propose a novel approach to regularize deep registration with a deformation vextor field (DVF) representation model using computed tomography angiography (CTA). In the form of a convolutional auto-encoder, the MRM was trained to capture the spatially variant pattern of feasible DVF Jacobian. The CTA-derived MRM was then incorporated into an unsupervised network to facilitate MRI registration. In the experiment, 10 CTAs were used to derive the MRM. The method was tested on 10 0.35 T scans in long-axis view with manual segmentation and 15 3 T scans in short-axis view with tagging-based landmarks.Introducing the MRM improved registration accuracy and achieved 2.23, 7.21, and 4.42 mm 80% Hausdorff distance on left ventricle, right ventricle, and pulmonary artery, respectively, and 2.23 mm landmark registration error. The results were comparable to carefully tuned SimpleElastix, but reduced the registration time from 40 s to 0.02 s. The MRM presented good robustness to different DVF sample generation methods.The model enjoys high accuracy as meticulously tuned optimization model and the efficiency of deep networks.The method enables model to go beyond the quality limitation of MRI. The robustness to training DVF generation scheme makes the method attractive to adapting to the available data and software resources in various clinics.

Background Use of oral contraceptives (OCs) may modulate the clinical course of women with congenital long QT syndrome (LQTS). The safety of OC use by sex hormone content has not been assessed in women with LQTS. Objective We aimed to evaluate the association of OCs with the risk of cardiac events (CEs) in women with LQTS. Methods Beginning in 2010, information on menarche onset, OC use, pregnancy, and menopause were obtained from women enrolled in the Rochester LQTS Registry. Type of OC was categorized as progestin-only, estrogen-only, or combined (estrogen/progestin). Andersen-Gill multivariate modeling was used to evaluate the association of time-dependent OC use with the burden of CE (total number of syncope, aborted cardiac arrest, and LQTS-related sudden cardiac death) from menarche onset through 40 years. Findings were adjusted for genotype, corrected QT duration, and time-dependent β-blocker therapy. Results A total of 1659 women with LQTS followed through March 2021, of whom 370 (22%) were treated with an OC. During a cumulative follow-up of 35,797 years, there were a total of 2027 CE. Multivariate analysis showed that progestin-only OC was associated with a pronounced 2.8-fold (P = .01) increased risk of CEs in women who did not receive β-blocker therapy, while β-blockers were highly protective during progestin-only OC treatment (hazard ratio 0.22; P = .01; P = .006 for β-blocker-by-OC interaction). The risk associated with OC use without concomitant β-blocker treatment was pronounced in women with LQTS type 2. Conclusion Our findings suggest that progestin-only OC should not be administered in women with LQTS without concomitant β-blocker therapy. OCs should be used with caution in women with LQTS type 2.

Multidisciplinary Pulmonary Embolism Response Teams (PERTs) may improve the care of patients with a high risk of pulmonary embolism (PE). The impact of a PERT on long-term mortality has never been evaluated. An observational analysis was conducted of 137 patients before PERT implementation (between 2014 and 2015) and 231 patients after PERT implementation (between 2016 and 2019), presenting to the emergency department of an academic medical center with submassive and massive PE. The primary outcome was 6-month mortality, evaluated by univariate and multivariate analyses. PERT was associated with a sustained reduction in mortality through 6 months (6-month mortality rates of 14% post-PERT vs 24% pre-PERT, unadjusted hazard ratio of 0.57, Relative Risk Reduction of 43%, p = 0.025). There was a reduced length of stay following PERT implementation (9.1 vs 6.5 days, p = 0.007). Time from triage to a diagnosis of PE was independently predictive of mortality, and the risk of mortality was reduced by 5% for each hour earlier that the diagnosis was made. In conclusion, this study is the first to demonstrate an association between PERT implementation and a sustained reduction in 6-month mortality for patients with high-risk PE.

This study aimed to evaluate the risk of sustained life-threatening ventricular tachyarrhythmias (VTAs) after hospitalization for heart failure (HHF).HHF is common among patients with an implantable cardioverter-defibrillator (ICD).We analyzed all 5,511 ICD patients enrolled in the landmark MADIT (Multicenter Automatic Defibrillator Implantation Trial) and RAID (Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillator) trials. Multivariate Cox regression was used to evaluate the association of in-trial HHF occurrence with the risk of subsequent VTA and the composite end point of VTA or cardiac death.Mean age was 64 ± 11 years, 23% were women, 62% were ischemic, and 40% had cardiac resynchronization therapy with defibrillators. The 3-year cumulative rate of VTA subsequent to HHF was significantly higher than the corresponding rate without HHF (44% vs. 24%, respectively; p 0.001). After multivariable adjustment, time-dependent HHF was shown to be associated with a 79% increased risk for VTA and a 2.9-fold increased risk for VTA/cardiac death (p 0.001 for both). In-trial development of atrial tachyarrhythmia (ATA) was also identified as an independent risk factor for the VTA and VTA/cardiac death end points (hazard ratio [HR]: 1.59 and 1.43, respectively; p ≤ 0.001 for both) but did not affect the association of HHF with VTA. Subgroup analysis demonstrated that the association of HHF with the risk of subsequent VTA was maintained among risk subsets categorized by age, sex, history of ATA, and implantation indication, but was significantly more pronounced among patients with nonischemic versus ischemic cardiomyopathy (HR: 2.54 and 1.43, respectively; p for interaction = 0.017).HHF is a powerful risk factor for subsequent VTA in patients implanted with an ICD. These data may be used for improved risk stratification in this population.

Purpose Size-specific dose estimate (SSDE) is a metric that adjusts CTDIvol to account for patient size. While not intended to be an estimate of organ dose, AAPM Report 204 notes the difference between the patient organ dose and SSDE is expected to be 10-20%. The purpose of this work was therefore to evaluate SSDE against estimates of organ dose obtained using Monte Carlo (MC) simulation techniques applied to routine exams across a wide range of patient sizes. Materials and methods Size-specific dose estimate was evaluated with respect to organ dose based on three routine protocols taken from Siemens scanners: (a) brain parenchyma dose in routine head exams, (b) lung and breast dose in routine chest exams, and (c) liver, kidney, and spleen dose in routine abdomen/pelvis exams. For each exam, voxelized phantom models were created from existing models or derived from clinical patient scans. For routine head exams, 15 patient models were used which consisted of 10 GSF/ICRP voxelized phantom models and five pediatric voxelized patient models created from CT image data. For all exams, the size metric used was water equivalent diameter (Dw ). For the routine chest exams, data from 161 patients were collected with a Dw range of ~16-44 cm. For the routine abdomen/pelvis exams, data from 107 patients were collected with a range of Dw from ~16 to 44 cm. Image data from these patients were segmented to generate voxelized patient models. For routine head exams, fixed tube current (FTC) was used while tube current modulation (TCM) data for body exams were extracted from raw projection data. The voxelized patient models and tube current information were used in detailed MC simulations for organ dose estimation. Organ doses from MC simulation were normalized by CTDIvol and parameterized as a function of Dw . For each patient scan, the SSDE was obtained using Dw and CTDIvol values of each scan, according to AAPM Report 220 for body scans and Report 293 for head scans. For each protocol and each patient, normalized organ doses were compared with SSDE. A one-sided tolerance limit covering 95% (P = 0.95) of the population with 95% confidence (α = 0.05) was used to assess the upper tolerance limit (TU ) between SSDE and normalized organ dose. Results For head exams, the TU between SSDE and brain parenchyma dose was observed to be 12.5%. For routine chest exams, the TU between SSDE and lung and breast dose was observed to be 35.6% and 68.3%, respectively. For routine abdomen/pelvis exams, the TU between SSDE and liver, spleen, and kidney dose was observed to be 30.7%, 33.2%, and 33.0%, respectively. Conclusions The TU of 20% between SSDE and organ dose was found to be insufficient to cover 95% of the sampled population with 95% confidence for all of the organs and protocols investigated, except for brain parenchyma dose. For the routine body exams, excluding the breasts, a wider threshold difference of ~30-36% would be needed. These results are, however, specific to Siemens scanners.

PURPOSE: Water needs increase during pregnancy, and proper hydration is critical for maternal and fetal health. This study characterized weekly hydration status changes throughout pregnancy and examined change in response to a randomized, behavioral intervention. An exploratory analysis tested how underhydration during pregnancy was associated with birth outcomes. METHODS: The Healthy Mom Zone Study is a longitudinal, randomized-control trial intervention aiming to regulate gestational weight gain (GWG) in pregnant women with overweight/obesity (n=27). Fourteen women received standard of care; 13 women additionally received weekly guidance on nutrition, physical activity, water intake, and health-promoting behaviors. Hydration status was measured weekly via overnight urine osmolality (Uosm) from ~8–36 weeks gestation; underhydration was dichotomized (Uosm≥500 mOsm/kg). Gestational age- and sex-standardized birth weight and length z scores and percentiles were calculated. We used mixed-effect and linear regression models to test covariate-adjusted relationships. RESULTS: No differences existed in Uosm or other characteristics between control and intervention women at baseline. Significant interactions (p=0.01) between intervention and week of pregnancy on Uosm indicated intervention women maintained lower Uosm, whereas control women had a significant quadratic (inverse-U) relationship and greater Uosm in the second and early third trimesters. Results were consistent across robustness and sensitivity checks. Exploratory analyses suggest underhydration was associated with birth weight, but not length, in opposite ways in the second vs. third trimester. CONCLUSION: A multi-component behavioral intervention helped women with overweight/obesity maintain better hydration throughout pregnancy. Future studies should confirm birth outcome results as they have important implications for early life nutrition. Trial Registration ClinicalTrials.gov Identifier: NCT03945266; registered May 10, 2019 retrospectively

There are limited data on the association of smoking with the risk of stroke following left ventricular assist device (LVAD) implantation. We designed this study to analyze the impact of smoking status at the time of LVAD implantation on stroke. We hypothesized that current smokers are at increased risk of stroke when compared with patients who were former or never smokers. The study population comprised of 369 patients in the University of Rochester Medical Center LVAD database, implanted with an LVAD between 2008 and 2018. Patients were stratified as current smoker (smoking within 30 days before LVAD implantation), former smoker, and never smoker. Stroke was defined as a transient ischemic attack or cerebrovascular accident (hemorrhagic or ischemic). There were 45 current smokers, 198 former smokers, and 125 never smokers. Current smokers were younger (mean age 50 ± 11 years), as compared with former (58 ± 12 years) and never smokers (56 ± 13 years) p < 0.001. At 2 years following LVAD implantation, the cumulative incidence of stroke was significantly higher among current smokers (39%) as compared with former and never smokers (16% and 15%, respectively; p = 0.022 for the overall difference during follow-up). In a multivariate model adjusted for significant clinical variables, current smoking was associated with a significant 88% (p = 0.018) higher risk of stroke when compared with all noncurrent smokers. In conclusion, our data suggest that LVAD candidates who are current smokers experience a significantly higher risk of stroke following device implantation.

Interventions have modest impact on reducing excessive gestational weight gain (GWG) in pregnant women with overweight/obesity. This two-arm feasibility randomized control trial tested delivery of and compliance with an intervention using adapted dosages to regulate GWG, and examined pre-post change in GWG and secondary outcomes (physical activity: PA, energy intake: EI, theories of planned behavior/self-regulation constructs) compared to a usual care group. Pregnant women with overweight/obesity (N = 31) were randomized to a usual care control group or usual care + intervention group from 8 to 2 weeks gestation and completed the intervention through 36 weeks gestation. Intervention women received weekly evidence-based education/counseling (e.g., GWG, PA, EI) delivered by a registered dietitian in a 60-min face-to-face session. GWG was monitored weekly; women within weight goals continued with education while women exceeding goals received more intensive dosages (e.g., additional hands-on EI/PA sessions). All participants used mHealth tools to complete daily measures of weight (Wi-Fi scale) and PA (activity monitor), weekly evaluation of diet quality (MyFitnessPal app), and weekly/monthly online surveys of motivational determinants/self-regulation. Daily EI was estimated with a validated back-calculation method as a function of maternal weight, PA, and resting metabolic rate. Sixty-five percent of eligible women were randomized; study completion was 87%; 10% partially completed the study and drop-out was 3%. Compliance with using the mHealth tools for intensive data collection ranged from 77 to 97%; intervention women attended > 90% education/counseling sessions, and 68–93% dosage step-up sessions. The intervention group (6.9 kg) had 21% lower GWG than controls (8.8 kg) although this difference was not significant. Exploratory analyses also showed the intervention group had significantly lower EI kcals at post-intervention than controls. A theoretical, adaptive intervention with varied dosages to regulate GWG is feasible to deliver to pregnant women with overweight/obesity.

Low systolic blood pressure (SBP) was previously suggested to be a marker for heart failure and mortality in patients with low left ventricular ejection fraction. We aimed to explore the association of SBP on risk of ventricular tachyarrhythmias (VTA) and atrial arrhythmias as well as appropriate and inappropriate Implantable Cardioverter Defibrillator (ICD) therapy. The study population comprised 1,481 of 1,500 (99%) patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy trial. Multivariate Cox proportional hazards regression modeling was used to identify the association of baseline SBP (recorded prior to ICD implantation) with the risk of VTA > 170 beats/min during follow-up (primary end point) and atrial arrhythmia, appropriate and inappropriate ICD therapy, hospitalization and death (secondary end points). SBP was dichotomized at 120 mm Hg (approximate mean and median) and was also assessed as a continuous measure. Multivariate analysis showed that each 10 mm Hg decrement in SBP was associated with corresponding 11% increased risk for VTA (p = 0.008). Low SBP (≤120 mm Hg) was associated with a significant 58% (p = 0.002) increased risk for VTA ≥170 beats/min; 53% (p = 0.019) increased risk for VTA ≥200 beats/min; and 65% (p = 0.001) increased risk for appropriate ICD therapy, as compared with SBP >120 mm Hg. Low SBP was not associated with increased risk of atrial arrhythmias, and inappropriate ICD therapy. In conclusion, in MADIT-RIT, SBP (≤120 mm Hg) predicted higher rates of VTA. These findings suggest that SBP may be utilized for VTA risk stratification in candidates for primary ICD therapy.

INTRODUCTION: Pulmonary embolism response teams (PERTs) were developed to assist with diagnosis, risk stratification, and management of intermediate and high-risk pulmonary embolism (PE) and have been shown to reduce 90-day mortality. The pharmacist’s role on the PERT is not well defined. OBJECTIVES: Describe the pharmacist’s role as a PERT member and determine if pharmacists can improve time to anticoagulation and promote use of low molecular weight heparin (LMWH) instead of unfractionated heparin (UFH). METHODS: A retrospective, observational study of adult patients with massive or submassive PE between January 2014 and May 2020. Patient demographics, clinical variables, anticoagulation treatment/timing, and pharmacist activities during PERT response were evaluated. Patients were divided into three groups for comparisons (pre-PERT vs post-PERT with a pharmacist vs post-PERT without a pharmacist). Wilcoxon rank-sum or Kruskal-Wallis test and chi-squared analysis were used for continuous and categorical data, respectively. RESULTS: A total of 573 patients were included (mean age 63.2 ± 15.6 years, 54% male, 78% submassive PE); 137 in the pre-PERT and 436 in the post-PERT groups. Within the post-PERT group, 305 patients (70%) had a pharmacist as a member of the PERT, of which 222 (73%) had a documented pharmacotherapy-related intervention/activity. Most (n = 178, 58%) involved a pharmacist facilitating ordering/administration of an anticoagulant/thrombolytic. Median time from diagnosis to anticoagulation was significantly reduced in the post-PERT groups (pre-PERT: 104 minutes [IQR 124.5], post-PERT with a pharmacist: 63 minutes [IQR 84], post-PERT without a pharmacist: 75.5 minutes [IQR 113], P = .0001). More patients in the post-PERT groups received LMWH compared to UFH when a pharmacist was involved vs without a pharmacist (69.5% vs 53.3%, P = .0019) and major bleeding events were reduced (pre-PERT: 14.6%, post-PERT with a pharmacist: 4.6%, and post-PERT without a pharmacist: 9.9%, P = .0013) CONCLUSION: Pharmacists have an active role on the PERT and their involvement was associated with a shorter diagnosis to anticoagulation time, increased LMWH use, and fewer major bleeding events.

Background Alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM) can lead to heart rhythm disturbances including complete heart block (CHB) and atrial and ventricular arrhythmias. Objective We aimed to evaluate the utility of long-term arrhythmia monitoring with an implantable cardiac monitor (ICM) after ASA. Methods Between February 2014 and March 2019, 56 patients with HCM undergoing ASA were enrolled in a prospective study and underwent ICM implantation. Kaplan-Meier survival analysis was used to assess the rate of ICM-detected arrhythmic events. Results The mean age was 59 ± 11 years, and 20 (36%) were women. The median (25th, 75th percentile) resting left ventricular outflow tract gradient obtained by echocardiography was 43 (22, 81) mm Hg. Greater than 1 septal perforating artery was injected in 48 patients (86%). The Kaplan-Meier cumulative rate of ICM-detected arrhythmic events at 18 months of follow-up was 71%, with an event rate of 43% occurring within 3 months of ASA. The cumulative rate of the ICM-detected first atrial fibrillation event at 18 months was 37%, and the corresponding rate of CHB was 19%. All atrial fibrillation and CHB events were actionable, leading to the initiation of anticoagulation and pacemaker implantation, respectively. No baseline demographic or procedural variables were identified as independent predictors of an increased risk of developing ICM-detected arrhythmic events. Conclusion After ASA, ICM is effective in capturing clinically actionable arrhythmic events in patients with HCM regardless of patient's baseline risk factors.

Pregnant women are at a high risk for experiencing sleep disturbances, excess energy intake, low physical activity, and excessive gestational weight gain (GWG). Scant research has examined how sleep behaviors influence energy intake, physical activity, and GWG over the course of pregnancy. This study conducted secondary analyses from the Healthy Mom Zone Study to examine between- and within-person effects of weekly sleep behaviors on energy intake, physical activity, and GWG in pregnant women with overweight/obesity (PW-OW/OB) participating in an adaptive intervention to manage GWG. The overall sample of N = 24 (M age = 30.6 years, SD = 3.2) had an average nighttime sleep duration of 7.2 h/night. In the total sample, there was a significant between-person effect of nighttime awakenings on physical activity; women with >1 weekly nighttime awakening expended 167.56 less physical activity kcals than women with

Clinical studies of heart failure (HF) generally utilize the 6-minute walk test (6MWT) for functional capacity (FC) assessment. However, data on the impact of cardiac resynchronization therapy (CRT) on 6MWT and its role to predict long-term outcomes in mild HF patients with CRT are lacking. We studied 1,381 subjects with mild HF enrolled in Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy with 6MWT data at baseline and 1 year. We assessed the effects of CRT-D on percent change in 6MWT at 1 year by left bundle branch block (LBBB) status, identified independent predictors of 6MWT at 1 year, and evaluated the association between changes in 6MWT and risk for HF or death. Treatment with CRT-D versus implantable cardiac defibrillator (ICD) was not associated with a significant improvement in 6MWT at 1-year in LBBB subjects (2.2 % vs 0.0%, p = 0.428, but it was associated with a deterioration in 6MWT in non-LBBB subjects (4.1% vs 0.0%, p = 0.308). Multivariate analysis showed that each 5% reduction in 6MWT was independently associated with a corresponding 3% increase in the risk of subsequent HF or death (p = 0.014). In conclusion, our findings suggest that 6MWT has limited utility to identify CRT response in mild HF subjects with LBBB. However, 6MWT showed a signal toward deterioration in mild HF subjects with non-LBBB, and this was predictive of subsequent increased risk of HF or death.

Background Studies of long-term inotrope use in advanced HF have previously provided limited and conflicting results. This study aimed to evaluate the safety and efficacy of long-term milrinone use and identify predictors of failure to bridge to orthotropic heart transplant (OHT) in a cohort of end-stage heart failure (HF) patients listed for heart transplantation and receiving inotrope therapy. Methods The study included 150 adults listed for OHT at a single center from 2001 to 2017 who received milrinone therapy for ≥30 days. Multivariate Cox proportional hazards models were used to identify factors associated with “failure” (left ventricular assist device, intra-aortic balloon pump, status downgrade due to instability, death) vs. “success” (OHT, recovery) during bridging to OHT. Results “Failure” occurred in 33 (22%) patients. Factors independently associated with failure included male sex (HR = 7.6; p = 0.004), no implantable cardioverter-defibrillator (HR = 3.8; p = 0.009), and lack of guideline-directed medical therapy (GDMT) with a beta-blocker (HR = 7.8; p = 0.002) or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (HR = 6.3; p Conclusions Our findings suggest that long-term milrinone therapy in selected patients is associated with a high rate of successful bridging to OHT and a low rate of adverse events. Patients intolerant of GDMT are more likely to fail to bridge to OHT without mechanical support. Sex differences in outcomes associated with milrinone therapy should be explored.

Background Implantable cardioverter-defibrillator (ICD) programming to novel settings can reduce the risk of inappropriate therapies. Objective The purpose of this study was to evaluate the impact of novel ICD programming after the first occurrence of ventricular tachycardia (VT). Methods In MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy) patients who experienced a first occurrence of VT, the risk of subsequent inappropriate and appropriate ICD therapies and adverse cardiovascular events by ICD programming to Arm A (conventional: VT ≥170 bpm), Arm B (high rate: VT ≥200 bpm), or Arm C (duration delay: ≥60-second delay before therapy ≥170 bpm) was determined. Results Among 205 patients, ICD programming changes were made in 30 patients (15%) after they experienced a VT episode; 117 patients (57%) were programmed to Arm A settings and 88 patients (43%) to Arm B/C settings. At 15-month follow-up, the cumulative probability of inappropriate ICD therapy was significantly lower in Arm B/C compared to Arm A (9% vs 20%; log-rank P = .029 for overall difference). The rate of appropriate ICD therapy also was significantly lower in Arm B/C compared to Arm A (32% vs 64%; log-rank P = .001 for overall difference). Multivariate analysis showed that patients programmed to Arm B/C after the occurrence of VT had a 71% reduction (P = .02) in the risk of inappropriate ICD therapies and a 43% reduction (P = .02) in the risk of appropriate ICD therapies compared to Arm A. Conclusion The benefit of high-rate cutoff or duration delay settings in patients with an ICD is maintained after the first occurrence of VT.

OBJECTIVES History of prior cardiac surgery has traditionally been considered a risk factor for subsequent cardiac procedures. The aim of this study was to investigate the outcomes of patients implanted with a left ventricular assist device via redo sternotomy. METHODS Prospectively collected data were reviewed for all patients implanted with a continuous-flow left ventricular assist device at a single institution from December 2006 through June 2018. Patients were separated into 2 cohorts: those with a history of prior cardiac surgery (redo sternotomy) and those undergoing primary sternotomy at the time of left ventricular assist device implantation. The primary outcome was overall survival. RESULTS Of the 321 patients included in the study, 77 (24%) were implanted via redo sternotomy and 244 (76%) via primary sternotomy. The redo sternotomy cohort was generally older (59 ± 10 vs 57 ± 12 years, P = 0.050) and had a higher incidence of ischaemic disease (70% vs 49%, P = 0.002). The Kaplan–Meier survival analysis demonstrated that overall survival was not significantly different between the redo sternotomy and primary sternotomy groups (6-month survival: 86% vs 92%; 5-year survival: 53% vs 51%; log-rank P = 0.590 for overall difference during follow-up). The propensity score analysis consistently showed that redo sternotomy was not significantly associated with mortality risk (hazard ratio 1.19, 95% confidence interval 0.73–1.93; P = 0.488). Redo sternotomy patients were more likely to require rehospitalization during their first year postoperatively (P = 0.020) and spent less time out of the hospital during the first year (P = 0.046). CONCLUSIONS The redo sternotomy cohort represents a more technically challenging patient population, but overall survival similar to that of primary sternotomy patients can be achieved.

We aimed to assess the predictors of new supraventricular tachycardia (SVT) and the association of new SVT with subsequent clinical outcomes among mild heart failure (HF) patients.The study population comprised patients enrolled in MADIT-CRT, after exclusion of patients with atrial arrhythmias before enrollment (N = 325). Multivariate analysis was used to identify predictors of new-onset SVT and the association of time-dependent development of SVT with subsequent ventricular tachyarrhythmic events (VTEs), HF-hospitalizations, and death. SVT burden was categorized into three groups based on the number of episodes per patient; (a) Low10, (b) Intermediate ≥10 but20, and (c) High ≥20. During mean follow up of 3.4 ± 1.1 years, 41(3%) subjects developed new SVT. African American race, diastolic blood pressure (DBP)80 mmHg and prior non sustained ventricular arrhythmia were independent predictors for SVT. Multivariate analysis showed that the development of time-dependent SVT was associated with a4-fold increased risk for VTEs (HR = 4.3; 95% CI: 1.6-11.7; P = .004) and with a6-fold increased risk for all-cause mortality (HR = 6.5; 95% CI: 2.3-18.7; P .001), but not with HF hospitalizations (HR = 2.2; 95% CI: 0.7-7.2; P = .17). Intermediate, and high SVT-burden were each independent risk factors for death when compared with Low burden (HR = 9.1; P = .03, and HR = 19.4; P .001; respectively).In patients with mild HF, the development of new-onset SVT after device implantation is related to distinct baseline clinical and epidemiologic characteristics and is associated with a significant increase in subsequent adverse outcomes, including VTEs and death.

Background Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). Objectives This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. Methods This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. Results Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. Conclusions In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253)

Lung cancer is by far the leading cause of cancer death in the US. Recent studies have demonstrated the effectiveness of screening using low dose CT (LDCT) in reducing lung cancer related mortality. While lung nodules are detected with a high rate of sensitivity, this exam has a low specificity rate and it is still difficult to separate benign and malignant lesions. The ISBI 2018 Lung Nodule Malignancy Prediction Challenge, developed by a team from the Quantitative Imaging Network of the National Cancer Institute, was focused on the prediction of lung nodule malignancy from two sequential LDCT screening exams using automated (non-manual) algorithms. We curated a cohort of 100 subjects who participated in the National Lung Screening Trial and had established pathological diagnoses. Data from 30 subjects were randomly selected for training and the remaining was used for testing. Participants were evaluated based on the area under the receiver operating characteristic curve (AUC) of nodule-wise malignancy scores generated by their algorithms on the test set. The challenge had 17 participants, with 11 teams submitting reports with method description, mandated by the challenge rules. Participants used quantitative methods, resulting in a reporting test AUC ranging from 0.698 to 0.913. The top five contestants used deep learning approaches, reporting an AUC between 0.87 - 0.91. The team's predictor did not achieve significant differences from each other nor from a volume change estimate (p =.05 with Bonferroni-Holm's correction).

This chapter covers the use of computed tomography (CT) in quantitative imaging (QI). The use of CT in clinical practice and its widespread use in many clinical applications are described, and a short history of QI applications is presented. Some of these have been in place for 30 years. A full understanding of the use of CT as a clinical QI measurement system requires knowledge of some of the design features of modern CT scanners and their capabilities, including the number of detector rows, the design of those detectors, the number and characteristics of the x-ray source, and filtration schemes. Also important are issues related to operational parameters of CT scanning, including acquisition and reconstruction parameters, and their effects on QI and radiomic feature sensitivity. The chapter concludes with a brief discussion of standardization, with regard to the use of CT in QI applications.

Background and study aims Left ventricular assist device (LVAD) placement is a therapeutic modality for patients with end-stage heart failure. Gastrointestinal bleeding is a common complication following LVAD implantation. The aim of this study was to report our experience in management and outcomes of gastrointestinal bleeding in a large cohort of patients with LVADs. Patients and methods We performed a retrospective review of all patients who underwent LVAD implantation at the University of Rochester Medical Center from January 2008 to June 2017. Data were collected on patient characteristics, clinical aspects of gastrointestinal bleeding events, and procedural interventions. A Cox proportional hazard model was utilized to identify potential risk factors for a gastrointestinal bleeding event. Results During the study period, 345 patients underwent LVAD implantation. Of these, 125 patients (36.2 %) experienced 297 gastrointestinal bleeding events resulting in 533 endoscopic procedures. The diagnostic yield of endoscopy in determining a bleeding source was 49.5 %. If required, therapeutic interventions were successful in achieving homeostasis in 96.2 % of procedures. Our 30-day overall post-procedure adverse event (AE) rate was 6.6 %. Procedure-related (bleeding, infection, and perforation) AEs were very minimal (2.8 %). A Cox proportional hazard model indicated that older age at implant, female sex, African-American race, diabetes mellitus, and pulmonary hypertension were statistically significant predictors of a gastrointestinal bleeding event following LVAD implantation. Conclusions LVAD patients have a high risk of gastrointestinal bleeding. Endoscopy was able to safely locate a bleeding lesion in approximately half of our patients and was successful in treating bleeding lesions in a majority of the cases.

Aims To explore the association between resting heart rate (RHR) and ventricular tachyarrhythmias (VTA) events among patients who were enrolled in MADIT-RIT. Methods and results Multivariate Cox proportional hazards regression modelling was employed to evaluate the association between baseline RHR [dichotomized at the lower quartile (≤63 b.p.m.) and further assessed as a continuous measure] and the risk for any VTA, fast VTA (>200 b.p.m.), and appropriate implantable cardioverter-defibrillator (ICD) therapy, among 1500 patients who were enrolled in MADIT-RIT. Kaplan–Meier survival analysis showed that at 2 years of follow-up the rate of any VTA was significantly lower among patients with low baseline RHR (≤63 b.p.m.) as compared with faster RHR (11% vs. 19%, respectively; P = 0.001 for the overall difference during follow-up). Similar results were shown for the association with the rate of fast VTA (8% vs. 14%, respectively; P = 0.016), and appropriate ICD therapy (10% vs. 18%, respectively; P = 0.004). Multivariate analysis, after adjustment for medical therapy, showed that low baseline RHR was associated with a significant 45% (P = 0.002) reduction in the VTA risk as compared with faster baseline RHRs. When assessed as a continuous measure, each 10 b.p.m. decrement in RHR was associated with a corresponding 13% (P = 0.014) reduction in the VTA risk. Conclusion In MADIT-RIT, low RHR was independently associated with a lower risk for life-threatening arrhythmic events. These findings suggest a possible role for RHR for improved selection of candidates for ICD therapy.

BACKGROUND Left ventricular assist devices (LVADs) have improved outcomes for selected patients with advanced heart failure, but alternative optimal surgical techniques remain to be defined. We aim to describe our initial experience in using a sternal-sparing (SS) technique for implantation of a magnetically levitated LVAD, the HeartMate 3 (HM3) pump. METHODS This retrospective, single-center study included consecutive patients implanted with the HM3 LVAD between September 2015 and September 2018. Patients were compared based on surgical approach: SS or traditional sternotomy (TS). The primary outcome was overall survival at 6 months. Secondary outcomes included peri-operative complications, blood product utilization, and hospital readmissions. RESULTS Of 105 patients implanted with the HM3 LVAD, 41 (39%) were implanted via SS and 64 (61%) via TS approach. There were no intraoperative conversions. The SS patients were younger; otherwise, all other characteristics were similar between cohorts. The SS cohort demonstrated a significantly lower incidence of severe right ventricular failure (7% vs 28%, p = 0.012), fewer blood-product transfusions (41% vs 86%, p < 0.001), and shorter index hospital length of stay (15.5 vs 21 days, p = 0.018). Six-month survival was 93% for the SS cohort. CONCLUSIONS In this single-center observational study, we have demonstrated that the SS approach may be a safe and effective surgical technique for implantation of the HM3 LVAD in well-selected patients. The potential benefits compared with TS require further inquiry.

Introduction: Long QT syndrome (LQTS) mutation carriers have elevated the risk of cardiac events even in the absence of QTc prolongation; however, mutation penetrance in patients with normal QTc may be reflected in abnormal T-wave shape, particularly in KCNH2 mutation carriers. We aimed to assess whether the magnitude of a three-dimensional T-wave vector (TwVM) will identify KCNH2-mutation carriers with normal QTc at risk for cardiac events. Methods: Adult LQT2 patients with QTc < 460 ms in men and

The aim of this study was to evaluate the association between improvement in left ventricular end-systolic volume (LVESV) with cardiac resynchronization therapy (CRT) and mortality and whether this relationship was modified by the presence of a left bundle branch block (LBBB) electrocardiographic pattern.Left ventricular reverse remodeling in patients receiving CRT has been shown to predict outcomes. However, the extent to which reverse remodeling contributes to long-term survival is not well understood.Changes in LVESV were assessed in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) patients receiving CRT with a defibrillator (CRT-D) and echocardiograms available at 1 year (n = 752), stratified by LBBB, relative to long-term all-cause mortality, compared with those with implantable cardioverter-defibrillators (ICDs) only (n = 684).In patients with LBBB, a reduction in LVESV of35% (median) translated into significantly lower risk for long-term mortality (hazard ratio [HR]: 0.34; p 0.001), heart failure (HF) events (HR: 0.21; p 0.001), and HF or death (HR: 0.27; p 0.001) compared with patients with ICDs only. Patients with reductions in LVESV ≤35% had a significantly lower risk for HF, and HF or death, and a nonsignificantly lower rate of death compared with those with ICDs only (HR: 0.74; p = 0.13). Risk reduction in HF events was uniform across all LVESV quartiles. In patients without LBBB, there was no survival benefit (HR: 0.68; p = 0.271) despite an LVESV reduction greater than the median (27.6%). CRT-D patients without LBBB with the least reverse remodeling (quartile 1) had a more than 3-fold increased risk for death compared with those with ICDs only (HR: 3.11; p 0.001).In patients with LBBB, CRT-D-induced reduction in LVESV at 1 year is associated with long-term survival benefit. Despite left ventricular reverse remodeling with CRT-D, there is no survival benefit and potential harm in patients without LBBB.

PURPOSE Reducing dose level to achieve ALARA is an important task in diagnostic and therapeutic applications of computed tomography (CT) imaging. Effective image quality enhancement strategies are crucial to compensate for the degradation caused by dose reduction. In the past few years, deep learning approaches have demonstrated promising denoising performance on natural/synthetic images. This study tailors a neural network model for (ultra-)low-dose CT denoising, and assesses its performance in enhancing CT image quality and emphysema quantification. METHODS The noise statistics in low-dose CT images has its unique characteristics and differs from that used in general denoising models. In this study, we first simulate the paired ultra-low-dose and targeted high-quality image of reference, with a well-validated pipeline. These paired images are used to train a denoising convolutional neural network (DnCNN) with residual mapping. The performance of the DnCNN tailored to CT denoising (DnCNN-CT) is assessed over various dose reduction levels, with respect to both image quality and emphysema scoring quantification. The possible over-smoothing behavior of DnCNN and its impact on different subcohort of patients are also investigated. RESULTS Performance evaluation results showed that DnCNN-CT provided significant image quality enhancement, especially for very-low-dose level. With DnCNN-CT denoising on 3%-dose cases, the peak signal-to-noise ratio improved by 8 dB and the structure similarity index increased by 0.15. This outperformed the original DnCNN and the state-of-the-art nonlocal-mean-type denoising scheme. Emphysema mask was also investigated, where lung voxels of abnormally low attenuation coefficient were marked as potential emphysema. Emphysema mask generated after DnCNN-CT denoising on 3%-dose image was demonstrated to agree well with that from the full-dose reference. Despite over-smoothing in DnCNN denoising, which contributed to slight underestimation of emphysema score compared to the reference, such minor overcorrection did not affect clinical conclusions. The proposed method provided effective detection for cases with appreciable emphysema while serving as a reasonable correction for normal cases without emphysema. CONCLUSIONS This work provides a tailored DnCNN for (ultra-)low-dose CT denoising, and demonstrates significant improvement on both the image quality and the clinical emphysema quantification accuracy over various dose levels. The clinical conclusion of emphysema obtained from the denoised low-dose images agrees well with that from the full-dose ones.

Objectives This study sought to determine the association of cardiomyopathy etiology with the likelihood of ventricular arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, and mortality. Background There are conflicting data on the benefit of primary prevention ICD therapy in patients with ischemic versus nonischemic cardiomyopathy (ICM/NICM). Methods The study population comprised 4803 patients with ICM (n = 3,106) or NICM (n = 1,697) with a primary prevention ICD enrolled in 5 randomized trials conducted between 1997 and 2017. The primary end point was sustained ventricular tachycardia (VT) ≥200 beats/min or ventricular fibrillation (VF). Secondary end points included appropriate ICD therapy and all-cause mortality. Differences in cause-specific mortality, including noncardiac, sudden cardiac, and non-sudden cardiac death, were also examined. Results Patients with ICM were significantly older and had more comorbid conditions, whereas those with NICM had a more advanced heart failure class at enrollment and were more often prescribed medical or cardiac resynchronization therapy for heart failure. Multivariate analysis showed that ICM versus NICM had a similar risk of VT/VF events (HR: 0.98 [95% CI: 0.79-1.20]) and appropriate ICD therapy (HR: 1.03 [95% CI: 0.87-1.22]), whereas the risk of all-cause mortality was 1.8-fold higher among ICM versus NICM patients (HR: 1.84 [95% CI: 1.42-2.38]), dominated by non-sudden cardiac mortality. Conclusions Combined data from 5 landmark ICD clinical trials show that ICM patients experience a similar risk of life-threatening ventricular arrhythmic events but have an increased risk of all-cause mortality, dominated by non-sudden cardiac death, compared with NICM patients.

The effectiveness of implantable cardioverter-defibrillators (ICDs) on reducing mortality has not been well studied in patients with long QT syndrome (LQTS).This study aimed to assess the survival benefits of ICDs in the overall LQTS population and in subgroups defined by ICD indications.This study included 3,035 patients (597 with ICD) from the Rochester LQTS Registry with a QTc ≥470 milliseconds or confirmed LQTS mutation. Using multivariable Cox proportional hazards models, the risk of all-cause mortality, all-cause mortality before age 50 years, and sudden cardiac death (SCD) were estimated as functions of time-dependent ICD therapy. Indication subgroups examined included patients with: 1) nonfatal cardiac arrest; 2) syncope while on beta-blockers; and 3) a QTc ≥500 milliseconds and syncope while off beta-blockers.During the 118,837 person-years of follow-up, 389 patients died (137 before age 50 years, and 116 experienced SCD). In the entire population, patients with ICDs had a lower risk of death (HR: 0.54; 95% CI: 0.34-0.86), death before age 50 years (HR: 0.29; 95% CI: 0.14-0.61), and SCD (HR: 0.22; 95% CI: 0.09-0.55) than patients without ICDs did. Patients with ICDs also had a lower risk of mortality among the 3 indication subgroups (HR: 0.14; 95% CI: 0.06-0.34; HR: 0.27; 95% CI: 0.10-0.72; and HR: 0.42; 95% CI: 0.19-0.96, respectively).ICD therapy was associated with a lower risk of all-cause mortality, all-cause mortality before age 50 years, and SCD in the LQTS population, as wells as with a lower risk of all-cause mortality in indication subgroups. This study provides evidence supporting ICD implantation in patients with high-risk LQTS.

Background We aimed to provide personalized risk estimates for cardiac events (CEs) and life‐threatening events in women with either type 1 or type 2 long QT. Methods and Results The prognostic model was derived from the Rochester Long QT Syndrome Registry, comprising 767 women with type 1 long QT (n=404) and type 2 long QT (n=363) from age 15 through 60 years. The risk prediction model included the following variables: genotype/mutation location, QTc‐specific thresholds, history of syncope, and β‐blocker therapy. A model was developed with the end point of CEs (syncope, aborted cardiac arrest, or long QT syndrome–related sudden cardiac death), and was applied with the end point of life‐threatening events (aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shocks). External validation was performed with data from the Mayo Clinic Genetic Heart Rhythm Clinic (N=467; type 1 long QT [n=286] and type 2 long QT [n=181]). The cumulative follow‐up duration among the 767 enrolled women was 22 243 patient‐years, during which 323 patients (42%) experienced ≥1 CE. Based on genotype‐phenotype data, we identified 3 risk groups with 10‐year projected rates of CEs ranging from 15%, 29%, to 51%. The corresponding 10‐year projected rates of life‐threatening events were 2%, 5%, and 14%. C statistics for the prediction model for the 2 respective end points were 0.68 (95% CI 0.65–0.71) and 0.71 (95% CI 0.66–0.76). Corresponding C statistics for the model in the external validation Mayo Clinic cohort were 0.65 (95% CI 0.60–0.70) and 0.77 (95% CI 0.70–0.84). Conclusions This is the first risk prediction model that provides absolute risk estimates for CEs and life‐threatening events in women with type 1 or type 2 long QT based on personalized genotype‐phenotype data. The projected risk estimates can be used to guide female‐specific management in long QT syndrome.

Background Outcomes of patients with nonischemic cardiomyopathy and low ejection fraction implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D), especially in contemporary, real-life cohorts, are not fully understood. Objective We aimed to better characterize outcomes of death and ventricular tachyarrhythmias in patients with nonischemic cardiomyopathy, implanted with an ICD or CRT-D, and specifically assess differences by sex. Methods The AnaLysIs of Both Sex and Device Specific FactoRs on Outcomes in PAtients with Non-Ischemic Cardiomyopathy (BIO-LIBRA) study was designed to prospectively assess outcomes of device-treated ventricular tachyarrhythmias and all-cause mortality events in nonischemic cardiomyopathy patients, indicated for an ICD or CRT-D implantation for the primary prevention of sudden cardiac death (SCD), with a specific focus on sex differences. We will enroll a total of 1000 subjects across 50 U.S. sites and follow patients for up to 3 years. Results The primary objective of BIO-LIBRA is to evaluate the combined risk of all-cause mortality and treated ventricular tachycardia (VT) or ventricular fibrillation (VF) events by subject sex and by implanted device type. We will also assess all-cause mortality, VT or VF alone, cardiac death, and SCD in the total cohort, as well as by subject sex and by the implanted device type. In addition, the previously validated Seattle Proportional Risk Model (SPRM) will be used to compare the SPRM predicted incidence of SCD to the observed incidence. Conclusions The BIO-LIBRA study will provide novel and contemporary information regarding outcomes in patients with a NICM who receive a defibrillator.

Author(s): Layman, Rick R; Hardy, Anthony J; Kim, Hyun J; Chou, Ei Ne; Bostani, Maryam; Cagnon, Chris; Cody, Dianna; McNitt-Gray, Michael | Abstract: PurposeThe purpose of this work was to estimate and compare breast and lung doses of chest CT scans using organ-based tube current modulation (OBTCM) to those from conventional, attenuation-based automatic tube current modulation (ATCM) across a range of patient sizes.MethodsThirty-four patients (17 females, 17 males) who underwent clinically indicated CT chest/abdomen/pelvis (CAP) examinations employing OBTCM were collected from two multi-detector row CT scanners. Patient size metric was assessed as water equivalent diameter (Dw ) taken at the center of the scan volume. Breast and lung tissues were segmented from patient image data to create voxelized models for use in anMonte Carlontransport code. The OBTCM schemes for the chest portion were extracted from the raw projection data. ATCM schemes were estimated using a recently developed method.nBreast and lungndoses for each TCM scenario were estimated for each patient model. CTDIvol -normalized breast (nDbreast ) and lung (nDlung ) dosesnwere subsequently calculated. The differences between OBTCM and ATCM normalized organ dose estimates were tested using linear regression models that included CT scanner and Dw as covariates.ResultsMean dose reduction from OBTCM in nDbreast was significant after adjusting for the scanner models and patient size (Pn=n0.047). When pooled with females and male patient, mean dose reduction from OBTCM in nDlung was observed to be trending after adjusting for the scanner model and patient size (Pn=n0.085).ConclusionsOne specific manufacturer's OBTCM was analyzed. OBTCM was observed to significantly decrease normalized breast relative to a modeled version of that same manufacturer's ATCM scheme. However, significant dose savings were not observed in lung dose over all. Results from this study support the use of OBTCM chest protocols for females only.

Registration between phases in 4D cardiac MRI is essential for reconstructing high-quality anatomy and appreciating the dynamics. Complex sequential compartmental motion and heterogeneous image quality make it challenging to design regularization functionals in classic optimization settings. In this study, we propose to introduce a novel motion representation model (MRM) into an image registration network to impose spatially variant prior for cardiac motion. A set of highly representative deformation vector fields (DVFs) were generated from high-contrast CTA images. In the form of a convolutional auto-encoder, the MRM was trained to capture the spatial variant pattern of the DVF Jacobian. The CT-derived MRM was then incorporated into an unsupervised network to facilitate 4D MRI registration. Our method was evaluated on ten 4D MRI scans with multi-compartment manual segmentations and achieved 2.25 mm target registration errors (TRE) on left ventricle. Compared to networks without MRM, introduction of the MRM reduced TREs on two ventricles and pulmonary artery with statistical significance. Compared to the tuned SimpleElastix, our method achieved comparable results on all compartments without statistical significance, but with a much shorter registration time of 0.02 s.

There are conflicting data on the impact of implantable cardioverter-defibrillator (ICD) shocks on subsequent mortality.The aim of this study was to determine whether the arrhythmic substrate leading to ICD therapy or the therapy itself increases mortality.The study cohort included 5,516 ICD recipients who were enrolled in 5 landmark ICD trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, RAID). The authors evaluated the association of device therapy with subsequent mortality in 4 separate time-dependent models: model I, type of ICD therapy; model II, type of arrhythmia for which ICD therapy was delivered; model III, combined assessment of all arrhythmia and therapy types during follow-up; and model IV, incremental risk associated with repeated ICD shocks.When analyzed by the type of ICD therapy (model I), a first appropriate ICD shock was associated with increased risk of subsequent mortality with or without concomitant occurrence of inappropriate shock during follow-up (hazard ratio [HR]: 2.78 and 2.31; p 0.001 and p = 0.12), whereas inappropriate shock alone was not associated with mortality risk (HR: 1.23; p = 0.42). Similarly, ICD therapy for ventricular tachycardia (VT) ≥200 beats/min or ventricular fibrillation (VF) (model II) was associated with increased risk of death with or without concomitant therapy for VT 200 beats/min (HRs: 2.25 and 2.62; both p 0.001), whereas appropriate therapy for VT 200 beats/min or inappropriate therapy (regardless of etiology) did not reach statistical significance (all p0.10). Combined assessment of all therapy and arrhythmia types during follow-up (model III) showed that appropriate ICD shocks for VF, shocks for fast VT (≥200 beats/min) without prior antitachycardia pacing (ATP), as well as shocks for fast VT delivered after failed ATP, were associated with the highest risk of subsequent death (HR: all2.8; p 0.001). Finally, 2 or more ICD appropriate shocks were not associated with incremental risk to the first appropriate ICD shock (model IV).The combined data from 5 landmark ICD trials suggest that the underlying arrhythmic substrate rather than the ICD therapy is the more important determinant of mortality in ICD recipients.

Introduction Cardiac resynchronization therapy (CRT) may be pro‐arrhythmic in patients with non‐left bundle branch block (non‐LBBB). We hypothesized that combined assessment of risk factors (RF) for ventricular tachyarrhythmias (VTAs) can be used to stratify non‐LBBB patients for CRT implantation. Methods The study comprised 412 non‐LBBB patients from MADIT‐CRT randomized to CRT‐D (n = 215) versus ICD only (n = 197). Best‐subset regression analysis was performed to identify RF associated with increased VTA risk in CRT‐D patients without LBBB. The primary end point was first occurrence of sustained VTA during follow‐up. Secondary end points included VTA/death and appropriate shock. Results Four RFs were associated with increased VTA risk: blood urea nitrogen >25mg/dl, ejection fraction

A novel physics-based data augmentation (PBDA) is introduced, to provide a representative approach to introducing variance during training of a deep-learning model. Compared to traditional geometric-based data augmentation (GBDA), we hypothesize that PBDA will provide more realistic variation representative of potential imaging conditions that may be seen beyond the initial training data, and thereby train a more robust model (particularly in the scope of medical imaging). PBDA is tested in the context of false-positive reduction in nodule detection in low-dose lung CT and is shown to exhibit superior performance and robustness across a wide range of imaging conditions.

PurposeRecent studies have demonstrated a lack of reproducibility of radiomic features in response to variations in CT parameters. In addition, reproducibility of radiomic features has not been well established in clinical datasets. We aimed to investigate the effects of a wide range of CT acquisition and reconstruction parameters on radiomic features in a realistic setting using clinical low dose lung cancer screening cases. We performed univariable and multivariable explorations to consider the effects of individual parameters and the simultaneous interactions between three different acquisition/reconstruction parameters of radiation dose level, reconstructed slice thickness, and kernel.MethodA cohort of 89 lung cancer screening patients were collected that each had a solid lung nodule >4mm diameter. A computational pipeline was used to perform a simulation of dose reduction of the raw projection data, collected from patient scans. This was followed by reconstruction of raw data with weighted filter back projection (wFBP) algorithm and automatic lung nodule detection and segmentation using a computer-aided detection tool. For each patient, 36 different image datasets were created corresponding to dose levels of 100%, 50%, 25%, and 10% of the original dose level, three slice thicknesses of 0.6mm, 1mm, and 2mm, as well as three reconstruction kernels of smooth, medium, and sharp. For each nodule, 226 well-known radiomic features were calculated at each image condition. The reproducibility of radiomic features was first evaluated by measuring the intercondition agreement of the feature values among the 36 image conditions. Then in a series of univariable analyses, the impact of individual CT parameters was assessed by selecting subsets of conditions with one varying and two constant CT parameters. In each subset, intraparameter agreements were assessed. Overall concordance correlation coefficient (OCCC) served as the measure of agreement. An OCCC≥0.9 implied strong agreement and reproducibility of radiomic features in intercondition or intraparameter comparisons. Furthermore, the interaction of CT parameters in impacting radiomic feature values was investigated via ANOVA.ResultsAll included radiomic features lacked intercondition reproducibility (OCCC50% of radiomic features.ConclusionWe systematically explored the multidimensional space of CT parameters in affecting lung nodule radiomic features. Univariable and multivariable analyses of this study not only showed the lack of reproducibility of the majority of radiomic features but also revealed existing interactions among CT parameters, meaning that the effect of individual CT parameters on radiomic features can be conditional upon other CT acquisition and reconstruction parameters. Our findings advise on careful radiomic feature selection and attention to the inclusion criteria for CT image acquisition protocols within the datasets of radiomic studies.

The role of cardiovascular implantable electronic device (CIED)-derived activity to predict implantable cardioverter-defibrillator (ICD) therapy or death is not known.We aimed to assess CIED-derived activity to predict clinical outcomes.In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily, then averaged for the first 30 days following randomization to predict inappropriate/appropriate therapy or death. Kaplan-Meier analysis and Cox proportional regression models were used to evaluate inappropriate/appropriate therapy, heart failure, or death by 30-day CIED-derived patient activity quintiles.There were 1463 patients with CIED activity data (98%). Patients in the highest quintile (Q5) of activity (more active) had the highest rate of inappropriate therapy, 21% at 2 years, as compared to 7%-11% in the other 4 quintiles (P.001), a 1.75 times higher risk (95% confidence interval [CI]: 1.23-2.50, P = .002). However, patients in the lowest quintile of activity (Q1, 1 hour/day) had the highest risk of mortality, 15% in 2 years, as compared to Q2-3 (1-2 hours/day, 8%-7% mortality), and Q4-5 (2 hours/day, 2%-3% mortality) (P.001). Patients with the lowest level of activity (Q1) had a 2.02 times higher risk of mortality (95% CI: 1.21-3.38, P = .007), and they had an 82% higher risk of heart failure hospitalization (95% CI: 1.28-2.57, P = .001).High CIED-derived 30-day median patient activity predicted inappropriate therapy, while low patient activity predicted mortality and heart failure in ICD and cardiac resynchronization therapy with defibrillator patients enrolled in MADIT-RIT. Device-derived activity assessment could serve as a useful predictor of outcomes.

Introduction: Statins may reduce risk for ventricular tachyarrhythmia (VTA) in patients with implantable cardioverter defibrillator (ICD). Ranolazine was shown to increase plasma concentrations of statin. Objective: To evaluate the effect of statin on recurrent VTA, and to explore the interaction with both Ranolizine and cardiomyopathy (CMP) origin. Methods: The Andersen-Gill extension of the Cox proportional hazards regression was used to assess the association between statin treatment and the risk for recurrent VTA among 1012 ICD patients enrolled in the Ranolazine Implantable Cardioverter-Defibrillator Trial (RAID). Interaction-term analysis with ranolazine and ischemic status were performed. Number of events was limited to a maximum of 10 VTA events per patient to avoid any patients having an undue influence on model estimates. Results: A total of 740 (73%) RAID patients were treated with statins. Multivariable analysis showed that statin use was associated with an overall 30% reduction in the risk for recurrent VTA (HR=0.70; ponly among patients with non-ischemic CMP (HR=0.53 [95%CI 0.41-0.69]; p Conclusion: Our findings suggest that treatment with statin (regardless if with or without ranolazine) is highly effective in reducing VTA burden in non-ischemic ICD recipients.

Introduction: Multidisciplinary Pulmonary Embolism Response Teams (PERTs) improve the care of patients with high risk pulmonary embolism (PE). The effect of a PERT on long-term mortality has never been evaluated. Hypothesis: We assessed the hypothesis that PERT would improve mortality of patients with high risk PE. Methods: An observational analysis was conducted of patients before PERT (pre-PERT, N = 137, between 2014 and 2015) after PERT (post-PERT, N = 231, from 2016 to 2019) presenting to the emergency department of a large academic medical center with submassive and massive PE. The primary outcome was six-month mortality with univariate and multivariate analyses. Results: PERT was associated with a sustained reduction in Kaplan-Meier mortality estimates (Figure) through six months (six-month mortality rates of 14% post-PERT vs. 24% pre-PERT, unadjusted HR of 0.57, RRR of 43%, NNT of 10, log-rank p=0.025). A Cox proportional hazards model demonstrated no difference in mortality from diagnosis through 1 month after presentation (HR 1.11 vs pre-PERT, 95% CI 0.55-2.26, p=0.766), but confirmed a reduction in mortality 1-6 months after diagnosis post-PERT (HR 0.42 vs pre-PERT, 95% CI 0.19-0.95, p=0.037). There was a reduced length of stay post-PERT (9.1± 10.8 vs 6.5 ± 9.8 days pre-PERT, P=0.007). Time from triage to diagnosis of PE was independently predictive of mortality, and the risk of mortality was reduced by 4.6% for each hour earlier that the diagnosis was made. Conclusions: In conclusion, this study is the first to demonstrate an association between PERT implementation and reduction in 6-month mortality in patients with high risk PE. This effect of reduced time to PE diagnosis associated with a multidisciplinary PERT may be a mechanism for the reduction in mortality.

Introduction: The Wearable Cardioverter Defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with a history of atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. Methods: In WEARIT-II, the cumulative probability of any sustained or non-sustained VT/VF (WCD-treated and non-treated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by negative binomial regression. Results: The WEARIT-II trial enrolled 2000 patients, 557 (28%) of whom had AF prior to enrollment. The cumulative probability of any sustained or non-sustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than in patients without AF (6% vs. 3%, p=0.001, Figure). Similarly, the recurrent rate of any sustained or non-sustained VT/VF was significantly higher in patients with prior AF vs. no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p=0.001). Patients with prior AF also had a significantly higher burden of WCD-detected atrial arrhythmias/SVT (64 events per 100 patient-years vs 13.7 events per 100 patient-years, p Conclusions: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.

Cardiac resynchronization therapy-defibrillator (CRT-D) may reduce the incidence of first ventricular tachyarrhythmia (VTA) in patients with heart failure (HF) and left bundle branch block (LBBB).The purpose of this study was to assess the effect of CRT-D on VTA burden in LBBB patients.We included 1281 patients with LBBB from MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy). VTA was defined as any treated or monitored sustained ventricular tachycardia (VT ≥180 bpm) or ventricular fibrillation (VF). Life-threatening VTA was defined as VT ≥200 bpm or VF. VTA recurrence was assessed using the Andersen-Gill model.During a mean follow-up of 2.5 years, 964 VTA episodes occurred in 264 patients (21%). The VTA rate per 100 person-years was significantly lower in the CRT-D group compared with the implantable cardioverter-defibrillator (ICD) group (20 vs 34; P .01). Multivariate analysis demonstrated that CRT-D treatment was associated with a 32% risk reduction for VTA recurrence (hazard ratio 0.68; 95% confidence interval 0.57-0.82; P.001), 57% risk reduction for recurrent life-threatening VTA, 54% risk reduction for recurrent appropriate ICD shocks, and 25% risk reduction for the combined endpoint of VTA and death. The effect of CRT-D on VTA burden was consistent among all tested subgroups but was more pronounced among patients in New York Heart Association functional class I. Landmark analysis showed that at 2 years, the cumulative probability of death subsequent to year one was highest (16%) among patients who had ≥2 VTA events during their first year.In patients with LBBB and HF, early intervention with CRT-D reduces mortality, VTA burden, and frequency of multiple appropriate ICD shocks. VTA burden is a powerful predictor of subsequent mortality.

Background Sex differences in outcome have been reported in patients with congenital long QT syndrome. We aimed to report on the incidence of time‐dependent life‐threatening events in male and female patients with long QT syndrome with an implantable cardioverter defibrillator (ICD). Methods and Results A total of 60 patients with long QT syndrome received an ICD for primary or secondary prevention indications. Life‐threatening events were evaluated from the date of ICD implant and included ICD shocks for ventricular tachycardia, ventricular fibrillation, or death. ICDs were implanted in 219 women (mean age 38±13 years), 46 girls (12±5 years), 55 men (43±17 years), and 40 boys (11±4 years). Mean follow‐up post‐ICD implantation was 14±6 years for females and 12±6 years for males. At 15 years of follow‐up, the cumulative probability of life‐threatening events was 27% in females and 34% in males (log‐rank P =0.26 for the overall difference). In the multivariable Cox model, sex was not associated with significant differences in risk first appropriate ICD shock (hazard ratio, 0.83 female versus male; 95% CI, 0.52–1.34; P =0.47). Results were similar when stratified by age and by genotype: long QT syndrome type 1 (LQT1), long QT syndrome type 2 (LQT2), and long QT syndrome type 3 (LQT3). Incidence of inappropriate ICD shocks was higher in males versus females (4.2 versus 2.7 episodes per 100 patient‐years; P =0.018), predominantly attributed to atrial fibrillation. The first shock did not terminate ventricular tachycardia/ventricular fibrillation in 48% of females and 62% of males ( P =0.25). Conclusions In patients with long QT syndrome with an ICD, the risk and rate of life‐threatening events did not significantly differ between males and females regardless of ICD indications or genotype. In a substantial proportion of patients with long QT syndrome, first shock did not terminate ventricular tachycardia/ventricular fibrillation.

Emergence of the COVID-19 crisis has catalyzed rapid paradigm shifts throughout medicine. Even after the initial wave of the virus subsides, a wholesale return to the prior status quo is not prudent. As a specialty that values the proper application of new technology, radiation oncology should strive to be at the forefront of harnessing telehealth as an important tool to further optimize patient care. We remain cognizant that telehealth cannot and should not be a comprehensive replacement for in-person patient visits because it is not a one for one replacement, dependent on the intention of the visit and patient preference. However, we envision the opportunity for the virtual patient “room” where multidisciplinary care may take place from every specialty. How we adapt is not an inevitability, but instead, an opportunity to shape the ideal image of our new normal through the choices that we make. We have made great strides toward genuine multidisciplinary patient-centered care, but the continued use of telehealth and virtual visits can bring us closer to optimally arranging the spokes of the provider team members around the central hub of the patient as we progress down the road through treatment.

Background Following cryptogenic stroke, guidelines recommend cardiac monitoring for occult atrial fibrillation (AF). We aimed to evaluate predictors of AF during long‐term implantable cardiac monitoring. Methods and Results We studied 293 consecutive patients who underwent implantable cardiac monitor implant (Medtronic LINQ) following hospitalization for cryptogenic stroke at the University of Rochester Medical Center from January 2013 to September 2018. Multivariable Cox proportional hazards regression modeling was used to identify predictors of AF during long‐term monitoring. At 36 months of follow‐up, the cumulative rate of implantable cardiac monitor–detected AF events was 32% in the total study population. Multivariable analysis identified age ≥70 years as the most powerful predictor of the development of AF events during follow‐up (hazard ratio, 2.28 [95% CI, 1.39–3.76]; P =0.001). Replacing age with the CHA 2 DS 2 ‐VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex category) score resulted in a weaker association, for which each 1‐point increment in the CHA 2 DS 2 ‐VASC score was associated with an 18% increased risk of developing AF (95% CI, 1.00–1.38; P =0.047). Consistent results were shown using Kaplan–Meier analysis by age and by the CHA 2 DS 2 VASc score. Conclusions Cryptogenic stroke patients continue to develop AF episodes during 36 months of implantable cardiac monitoring following the index event. Age is the most powerful predictor of occult AF in this population.

Aims The benefit of prophylactic implantable cardioverter-defibrillator (ICD) is not uniform due to differences in the risk of life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) and non-arrhythmic mortality. We aimed to develop an ICD benefit prediction score that integrates the competing risks. Methods and results The study population comprised all 4531 patients enrolled in the MADIT trials. Best-subsets Fine and Gray regression analysis was used to develop prognostic models for VT (≥200 b.p.m.)/VF vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF). Eight predictors of VT/VF (male, age 75 b.p.m., systolic blood pressure Conclusions We propose the novel MADIT-ICD benefit score that predicts the likelihood of prophylactic ICD benefit through personalized assessment of the risk of VT/VF weighed against the risk of non-arrhythmic mortality.

Background: Mild heart failure (HF) patients without left bundle branch block (LBBB) did not derive a significant reduction in risk of a HF event/death in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy). However, the efficacy of CRT with a defibrillator (CRT-D) may be modified after the development of the first hospitalization for HF (HHF). We aimed to study the effect of CRT-D on long-term risk of recurrent HHF in patients without LBBB in MADIT-CRT. Methods: Data on recurring HHF were collected for 1818 subjects. The CRT-D versus implantable cardioverter-defibrillator-only risk for first and subsequent HHF was assessed by QRS morphology in on-treatment analysis using Cox proportional hazards regression modeling. Results: During long-term follow-up, 412 patients had ≥1 HHF and 333 had ≥2 HHF. Multivariate analysis revealed that in LBBB patients, CRT-D, compared with implantable cardioverter-defibrillator, was associated with a significant reduction in risk of first and subsequent HHF (first: hazard ratio, 0.41 [95% CI, 0.31–0.54], P P P =0.808). However, after occurrence of a first HHF, CRT-D therapy was associated with a pronounced 44% reduction in risk of subsequent HHF (hazard ratio, 0.56 [95% CI, 0.32–0.97], P =0.039). Patients without LBBB with ≥1 HHF during the first year of follow-up demonstrated increasing dyssynchrony at 1 year compared with those who had no HHF ( P =0.016). Conclusions: In MADIT-CRT, we show a beneficial effect of CRT-D in patients without LBBB subsequent to development of a first HHF, possibly due to increased dyssynchrony associated with HF progression. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00180271, NCT01294449, and NCT02060110.

Background Data on the arrhythmic burden of women at risk for sudden cardiac death are limited, especially in patients using the wearable cardioverter-defibrillator (WCD). Objective We aimed to characterize WCD compliance, atrial and ventricular arrhythmic burden, and WCD outcomes by sex in patients enrolled in the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II U.S. Registry). Methods In the WEARIT-II Registry, we stratified 2000 patients by sex into women (n = 598) and men (n = 1402). WCD wear time, ventricular and atrial arrhythmic events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates at the end of WCD use were evaluated. Results The mean WCD wear time was similar in women and men (94 days vs 90 days; P = .145), with longer daily use in women (21.4 h/d vs 20.7 h/d; P = .001). Burden of ventricular tachycardia or ventricular fibrillation was higher in women, with 30 events per 100 patient-years compared with 18 events per 100 patient-years in men (P = .017), with similar findings for treated and non-treated ventricular tachycardia/ventricular fibrillation. Recurrent atrial arrhythmias/sustained ventricular tachycardia was also more frequent in women than in men (167 events per 100 patient-years vs 73 events per 100 patient-years; P = .042). However, ICD implantation rate at the end of WCD use was similar in both women and men (41% vs 39%; P = .448). Conclusion In the WEARIT-II Registry, we have shown a higher burden of ventricular and atrial arrhythmic events in women than in men. ICD implantation rates at the end of WCD use were similar. Our findings warrant monitoring women at risk for sudden cardiac death who have a high burden of atrial and ventricular arrhythmias while using the WCD.

Several institutions have developed image feature extraction software to compute quantitative descriptors of medical images for radiomics analyses. With radiomics increasingly proposed for use in research and clinical contexts, new techniques are necessary for standardizing and replicating radiomics findings across software implementations. We have developed a software toolkit for the creation of 3D digital reference objects with customizable size, shape, intensity, texture, and margin sharpness values. Using user-supplied input parameters, these objects are defined mathematically as continuous functions, discretized, and then saved as DICOM objects. Here, we present the definition of these objects, parameterized derivations of a subset of their radiomics values, computer code for object generation, example use cases, and a user-downloadable sample collection used for the examples cited in this paper.