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Background: Women with congenital long QT syndrome (LQTS) experience increased cardiac event risk after the onset of adolescence, perhaps stemming from the known modulating effects of sex hormones on the cardiac potassium channels. Objective: We hypothesized that the effect of sex hormones on cardiac ion channel function may modify electrocardiographic (ECG) parameters associated with the propensity for ventricular tachyarrhythmias during the menstrual cycle in women with LQTS. Methods: We prospectively enrolled 65 women with congenital LQTS (type 1 LQTS [LQT1], n = 24 [36.9%]; type 2 LQTS [LQT2], n = 20 [30.8%]) and unaffected female relatives (n = 21 [32.3%]). Patients underwent three 7-day ECG recordings during their menstrual cycles. Simultaneous saliva testing of sex hormone levels was conducted on the first day of each 7-day ECG recording cycle. Results: The mean age was 35 ± 8 years, without a significant difference among the groups. In women with LQT2, linear mixed effects models showed significant inverse correlations of the corrected QT interval with progesterone levels (P < .001) and with the progesterone to estradiol ratio (P < .001). Inverse relationships of the R-R interval with estradiol levels (P = .003) and of the T-wave duration with testosterone levels (P = .014) were also observed in women with LQT2. In contrast, no significant associations were observed between ECG parameters and sex hormone levels in women with LQT1 or unaffected relatives. Conclusion: This is the first study to prospectively assess correlations between repolarization dynamics and sex hormone levels during the menstrual cycle in women with congenital LQTS. Our findings show genotype-specific unique corrected QT dynamics during the menstrual cycle that may affect the propensity for ventricular tachyarrhythmia in women with LQTS, particularly women with LQT2.

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: 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

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.

Current guidelines for primary implantable cardioverter-defibrillator (ICD) therapy do not account for sex differences in arrhythmic risk in ICD candidates.To evaluate the association between sex and risk of ventricular tachyarrhythmia (VTA) and mortality.This cohort study compared differences in the risk of VTA and mortality between 4506 men and women enrolled in the 4 Multicenter Automatic Defibrillator Implantation Trials (MADIT) between July 1, 1997, and December 31, 2011. Data from prospective randomized controlled multicenter studies were analyzed retrospectively. Men and women with an ICD or cardiac resynchronization therapy defibrillator who were enrolled in all MADIT studies were included. Data were analyzed between January 10 and June 10, 2021.ICD implant.The primary end point was sustained VTA, defined as ICD-recorded, treated or monitored VTA at least 170/min or ventricular fibrillation. Secondary VTA end points included VTA at least 200/min, appropriate ICD shocks, and appropriate antitachycardia pacing. All end points were included in a first and recurrent event analysis.Of the 4506 study participants, 3431 were men (76%). Mean (SD) age of the cohort was 64 (12) years. For women vs men, the mean (SD) age (64 [12] years vs 64 [11] years) and left ventricular ejection fraction (24% vs 25%) were similar, but women exhibited a higher frequency of nonischemic cardiomyopathy (454 of 1075 women [42%] vs 2535 of 3431 men [74%]). Women had significantly lower 3-year cumulative probability of sustained VTA (16% vs 26%), fast VTA (9% vs 17%), and appropriate ICD shocks (7% vs 15%) compared with men (P .001 for all). Multivariable analysis showed that female sex was independently associated with at least 40% lower risk of all first and recurrent VTA end points (P .001 for all), including the primary end point (first event, HR = 60 [95% CI, 50-73], P .001; recurrent event, HR = 49 [95% CI, 43-55], P .001), after accounting for the competing risk of all-cause mortality and nonarrhythmic mortality. The lower VTA risk associated with female sex was consistent in risk subsets but was significantly more pronounced in patients with nonischemic cardiomyopathy (female vs male in the ischemic group: hazard ratio, 0.73 [95% CI, 0.56-0.95], P = .02; nonischemic group: hazard ratio, 0.50 [95% CI, 0.38-0.66], P .001; P = .03 for interaction between female sex and cardiomyopathy).Findings suggest that women display a significantly lower risk of first and recurrent life-threatening VTA events than men, and that it is more pronounced in patients with nonischemic cardiomyopathy, suggesting a need for sex-specific risk assessment for primary prevention ICD therapy.

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.

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.

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 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.

The new high-sensitivity cardiac troponin T (hs-cTnT) is now widely used in the United States.We aimed to examine outcomes associated with the introduction of the new 5The study comprised 5377 patients presenting to the ED with CV disorders between January and September 2018. Outcomes included rates of direct ED discharge, cardiac testing/procedures, and mortality. CV indications for troponin testing were categorized as rule-out acute coronary syndrome (RO-ACS) and other-CV (O-CV).Mean age was 62 ± 17 years, and 47% were female. Demographics and medical history did not differ significantly between the troponin groups. The use of hs-cTnT was associated with increased rates of direct discharge from the ED in the RO-ACS (48% vs. 37%; p0.01), but not in the O-CV (25% vs. 25%) cohort. Cardiac tests/procedures were more often performed after hs-cTnT vs. cTnT testing in both cohorts (45% vs. 41% for RO-ACS, and 33% vs. 28% for O-CV; p0.05 for both). Multivariate analysis demonstrated that hs-cTnT was not associated with a significant increase in postdischarge mortality in both cohorts (RO-ACS: hazard ratio = 1.47 [p = 0.13], O-CV: hazard ratio = 0.97 [p = 0.87]).Among patients with RO-ACS, hs-cTnT implementation resulted in increased rates of direct home discharge from the ED, without a significant increase in postdischarge mortality. Among patients presenting with O-CV indication, hs-cTnT implementation resulted in increased rates of cardiac testing procedures without an effect of ED discharge rates or long-term mortality.

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.

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.

Studies have reported sex differences in outcomes following implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) implantation. However, little is known about sex differences with regard to mode of death or device efficacy following ICD or CRT-D implantation.The purpose of this study was to investigate whether sex influenced mode of death or device efficacy in ICD and CRT-D subjects enrolled in the MADIT (Multicenter Automatic Defibrillator Implantation Trial) studies (MADIT-II, MADIT-CRT, and MADIT-RIT).The combined MADIT cohort consisted of 3038 men and 1000 women with ischemic cardiomyopathy (ICM) or nonischemic cardiomyopathy (NICM), left ventricular ejection fraction ≤30%; New York Heart Association functional class I-III heart failure who received ICD or CRT-D. Mode of death was divided into cardiac and noncardiac causes, reviewed by independent adjudication committees.A total of 295 men and 66 women died (9.7% vs 6.6%; P =.003) during 26 months. The most common cause of death was nonarrhythmic cardiac death in men (n = 121 [41%]) and noncardiac death in women (n = 22 [33%]). All-cause mortality and cardiac deaths were 1.5- to 2.0-fold higher in men vs women with ICM but similar for those with NICM after adjustment for covariates. ICD efficacy was similar in men and women, resulting in a 50% reduction in all-cause mortality. CRT-D was more effective at reducing all-cause and cardiac death in women than men.Mode of death differs between sex and is dependent on the underlying cardiac substrate. Compared to women, cardiac death is higher in men with ICM but similar in those with NICM. ICDs are equally effective at reducing mortality in both men and women. However, CRT-D may be more effective at reducing mortality in women.

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

(1) Background: Energy intake (EI) underreporting is a widespread problem of great relevance to public health, yet is poorly described among pregnant women. This study aimed to describe and predict error in self-reported EI across pregnancy among women with overweight or obesity. (2) Methods: Participants were from the Healthy Mom Zone study, an adaptive intervention to regulate gestational weight gain (GWG) tested in a feasibility RCT and followed women (n = 21) with body mass index (BMI) ≥25 from 8–12 weeks to ~36 weeks gestation. Mobile health technology was used to measure daily weight (Wi-Fi Smart Scale), physical activity (activity monitor), and self-reported EI (MyFitnessPal App). Estimated EI was back-calculated daily from measured weight and physical activity data. Associations between underreporting and gestational age, demographics, pre-pregnancy BMI, GWG, perceived stress, and eating behaviors were tested. (3) Results: On average, women were 30.7 years old and primiparous (62%); reporting error was −38% ± 26 (range: −134% (underreporting) to 97% (overreporting)), representing an ~1134 kcal daily underestimation of EI (1404 observations). Estimated (back-calculated), but not self-reported, EI increased across gestation (p < 0.0001). Higher pre-pregnancy BMI (p = 0.01) and weekly GWG (p = 0.0007) was associated with greater underreporting. Underreporting was lower when participants reported higher stress (p = 0.02) and emotional eating (p < 0.0001) compared with their own average. (4) Conclusions: These findings suggest systemic underreporting in pregnant women with elevated BMI using a popular mobile app to monitor diet. Advances in technology that allow estimation of EI from weight and physical activity data may provide more accurate dietary self-monitoring during pregnancy.

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.

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.

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.

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.

BACKGROUND We aimed to characterize the hourly, daily, and seasonally variations in the detection of new atrial fibrillation (AF) in heart failure patients implanted with a defibrillator. METHODS In 1309 patients enrolled in MADIT-RIT without AF at baseline, atrial arrhythmia data were analyzed from device interrogations. The circadian, weekly, and seasonal distribution of device detected AF was evaluated. The morning period was defined as 06:00-11:59, afternoon as 12:00-16:59, evening as 17:00-22:59, and the nighttime as 23:00-05:59. RESULTS During 17 months of follow-up, 66 (5%) patients developed new device-detected AF. AF patients were less likely to have ischemic cardiomyopathy and were more likely to have received an implantable cardioverter defibrillator rather than a cardiac resynchronization therapy with defibrillator. The highest number of AF occurred during the evening hours (25 patients [38%]) followed by a second peak in AF detection during the afternoon hours (21 patients [32%]). Importantly during the nighttime, new AF occurred only in three patients (4%). In comparison with the nighttime period, the odds ratio (OR) of developing AF during the evening time period was 8.5-fold higher (95% CI 7.3-9.7, P

Contains fulltext : 232932.pdf (Publisher’s version ) (Closed access) PURPOSE: Task Group Report 195 of the American Association of Physicists in Medicine contains reference datasets for the direct comparison of results among different Monte Carlo (MC) simulation tools for various aspects of imaging research that employs ionizing radiation. While useful for comparing and validating MC codes, that effort did not provide the information needed to compare absolute dose estimates from CT exams. Therefore, the purpose of this work is to extend those efforts by providing a reference dataset for benchmarking fetal dose derived from MC simulations of clinical CT exams. ACQUISITION AND VALIDATION METHODS: The reference dataset contains the four necessary elements for validating MC engines for CT dosimetry: (a) physical characteristics of the CT scanner, (b) patient information, (c) exam specifications, and (d) fetal dose results from previously validated and published MC simulations methods in tabular form. Scanner characteristics include non-proprietary descriptions of equivalent source cumulative distribution function (CDF) spectra and bowtie filtration profiles, as well as scanner geometry information. Additionally, for the MCNPX MC engine, normalization factors are provided to convert raw simulation results to absolute dose in mGy. The patient information is based on a set of publicly available fetal dose models and includes de-identified image data; voxelized MC input files with fetus, uterus, and gestational sac identified; and patient size metrics in the form of water equivalent diameter (Dw ) z-axis distributions from a simulated topogram (Dw,topo ) and from the image data (Dw,image ). Exam characteristics include CT scan start and stop angles and table and patient locations, helical pitch, nominal collimation and measured beam width, and gantry rotation time for each simulation. For simulations involving estimating doses from exams using tube current modulation (TCM), a realistic TCM scheme is presented that is estimated based upon a validated method. (d) Absolute and CTDIvol -normalized fetal dose results for both TCM and FTC simulations are given for each patient model under each scan scenario. DATA FORMAT AND USAGE NOTES: Equivalent source CDFs and bowtie filtration profiles are available in text files. Image data are available in DICOM format. Voxelized models are represented by a header followed by a list of integers in a text file representing a three-dimensional model of the patient. Size distribution metrics are also given in text files. Results of absolute and normalized fetal dose with associated MC error estimates are presented in tabular form in an Excel spreadsheet. All data are stored on Zenodo and are publicly accessible using the following link: https://zenodo.org/record/3959512. POTENTIAL APPLICATIONS: Similar to the work of AAPM Report 195, this work provides a set of reference data for benchmarking fetal dose estimates from clinical CT exams. This provides researchers with an opportunity to compare MC simulation results to a set of published reference data as part of their efforts to validate absolute and normalized fetal dose estimates. This could also be used as a basis for comparison to other non-MC approaches, such as deterministic approaches, or to commercial packages that provide estimates of fetal doses from clinical CT exams.

Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF 30%.Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF 30% and LVEF ≤ 30% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P 0.001 vs. HR 0.46, 95% CI 0.35-0.61, P 0.001; interaction P = 0.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups.In MADIT-CRT, left bundle branch block patients with higher LVEF ( 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling.ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110.

The authors aimed to evaluate the association of left ventricular (LV) lead location and long-term outcomes in MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy).There is limited data on the association of lead location with long-term clinical outcomes in patients with cardiac resynchronization therapy with defibrillator (CRT-D).The LV lead location was classified in 797 patients with CRT-D, in 569 patients with left bundle branch block (LBBB), in 228 patients with non-LBBB, and in 505 patients with an implantable cardioverter-defibrillator (ICD) only. Leads were classified into apical (n = 83) and non-apical (n = 486); with the non-apical LV leads further categorized into anterior (n = 99) and posterior/lateral (n = 387) within LBBB. All-cause mortality and heart failure (HF) events were assessed using Kaplan-Meier and Cox analyses.In CRT-D patients with LBBB and posterior/lateral LV lead location, there was an association with a significant reduction in long-term all-cause mortality (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.79; p = 0.001), and HF events (HR: 0.44, 95% CI: 0.33 to 0.60; p 0.001) compared to an ICD only, accompanied with better LV reverse remodeling. CRT-D patients with LBBB and an anterior LV lead location were shown to be associated with a significant reduction in HF events compared to an ICD only (anterior HR: 0.50, 95% CI: 0.30 to 0.82; p = 0.006); however, no association with mortality reduction was observed from CRT-D versus an ICD only. CRT-D was not associated with improved outcomes in non-LBBB patients, regardless of LV lead location.In mild HF patients with LBBB and an implanted CRT-D, lateral/posterior, and anterior LV lead locations are similarly associated with reduction in the risk of HF or death events compared to ICD alone. Mortality benefit derived from CRT-D is associated only with patients with lateral/posterior LV lead location. An apical LV lead location should be avoided due to the early risk of death whenever possible. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT], NCT00180271; Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Post Approval Registry [MADIT-CRT-PAR], NCT01294449; and MADIT-CRT Long-Term International Follow-Up Registry - Europe, NCT02060110).

Background The mitochondrial branched-chain aminotransferase (BCATm) is a recently discovered cancer marker with a poorly defined role in tumour progression. Methods To understand how a loss of function of BCATm affects cancer, the global knockout mouse BCATmKO was challenged with EL-4 lymphoma under different diet compositions with varying amounts of branched-chain amino acids (BCAAs). Next, the growth and metabolism of EL-4 cells were studied in the presence of different leucine concentrations in the growth medium. Results BCATmKO mice experienced delayed tumour growth when fed standard rodent chow or a normal BCAA diet. Tumour suppression correlated with 37.6- and 18.9-fold increases in plasma and tumour BCAAs, 37.5% and 30.4% decreases in tumour glutamine and alanine, and a 3.5-fold increase in the phosphorylation of tumour AMPK in BCATmKO mice on standard rodent chow. Similar results were obtained with a normal but not with a choice BCAA diet. Conclusions Global deletion of BCATm caused a dramatic build-up of BCAAs, which could not be utilised for energy or amino acid synthesis, ultimately delaying the growth of lymphoma tumours. Furthermore, physiological, but not high, leucine concentrations promoted the growth of EL-4 cells. BCATm and BCAA metabolism were identified as attractive targets for anti-lymphoma therapy.

Use of the wearable cardioverter-defibrillator (WCD) in older patients has not been described previously.The purpose of this study was to assess WCD wear time, risk of arrhythmic events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates after the end of WCD use in patients with age ≥65 years vs65 years.We stratified 1732 patients with ischemic and nonischemic cardiomyopathy from the Prospective Registry of Patients Using the Wearable Defibrillator Registry into 2 subgroups by age: those with age ≥65 years and those with age65 years. Wear time, arrhythmic events, and end-of-use decisions, specifically ICD implantation or improvement in ejection fraction, were evaluated for each age group.There were 722 patients with age ≥65 years (41.7%) and 1010 patients with age65 years (58.3%). Daily WCD wear time was longer in the older population (median 22.8 h/d (IQR 21.5 - 23.2) vs 22.3 h/d (IQR 19.5 - 23.0); P.001). Patients with age ≥65 years experienced higher event rates, per 100 patient-years, for any sustained ventricular tachycardia/ventricular fibrillation (31.95 vs 9.82; P = .027) and ventricular tachycardia/ventricular fibrillation treated with WCD shock (6.92 vs 2.37; P = .034), particularly with ischemic cardiomyopathy. Younger patients experienced a trend toward a higher event rate for atrial arrhythmias with nonischemic cardiomyopathy (150.07 vs 74.86; P = .055). At the end of WCD use, ICD implantation was more frequent in older patients (41.8% vs 36.5%; P = .034).Older patients had good compliance with the WCD, presented with more frequent ventricular arrhythmias, and were more likely to receive an ICD at the end of WCD use. The WCD may play a role in risk stratification of the older population.

Background Despite previous studies, the mortality risk of patients with diabetes mellitus after left ventricular assist device (LVAD) implant remains unclear. In addition, the relationship between the degree of glycemic control and long-term mortality risk in LVAD patients with diabetes has not been established. Methods Ninety-five nondiabetic patients and 96 diabetic patients from the University of Rochester Medical Center who received a HeartMate II (Thoratec, Pleasanton, CA) continuous-flow LVAD between May 2008 and June 2014 were included in this study. The primary outcome was all-cause mortality. Secondary outcomes included rates of infection, neurologic dysfunction, renal dysfunction, and rehospitalization. Kaplan-Meier survival analyses and Cox models were utilized. Results During follow-up, 32 diabetic patients (33%) and 15 nondiabetic patients (16%) died after LVAD implantation. Cumulative probability of death was higher for diabetic patients when compared with nondiabetic patients (42% versus 21% at 3 years, p = 0.013). There were no significant differences in overall rates of infection, neurologic dysfunction, and rehospitalization between the two groups. However, after an initial secondary outcome event, diabetic patients continued to have a higher mortality rate when compared with nondiabetic patients. There was no statistically significant difference in the risk of death between diabetic patients with pre-LVAD hemoglobin A1c less than 7.0% and diabetic patients with pre-LVAD hemoglobin A1c 7.0% or greater (hazard ratio 1.71, 95% confidence interval: 0.72 to 4.08, p = 0.223). Conclusions Diabetic patients who underwent LVAD implantation had a higher risk of death compared with nondiabetic patients. Adverse event rates did not differ between the two groups. Finally, the degree of glycemic control in diabetic patients before LVAD was not found to influence mortality.

Aims Prospective data regarding the role of implantable cardioverter-defibrillator (ICD) for the primary prevention of sudden cardiac death in patients with long QT syndrome (LQTS) is scarce. Herein, we explore the prospective Rochester LQTS ICD registry to assess the risk for appropriate shock in primary prevention in a real-world setting. Methods and results We studied 212 LQTS patients that had ICD implantation for primary prevention. Best-subsets proportional-hazards regression analysis was used to identify clinical variables that were associated with the first appropriate shock. Conditional models of Prentice, Williams, and Peterson were utilized for the analysis of recurrent appropriate shocks. During a median follow-up of 9.2 ± 4.9 years, there were 42 patients who experienced at least one appropriate shock and the cumulative probability of appropriate shock at 8 years was 22%. QTc ≥ 550 ms [hazard ratio (HR) 3.94, confidence interval (CI) 2.08-7.46; P