Risk of Sudden Cardiac Death in Patients Undergoing Cancer Treatment.

The risk of sudden cardiac death (SCD) in patients with cancer receiving cancer therapies is not well defined. In this study we aimed to (1) evaluate the risk of SCD during the first 6 months of cancer treatment and (2) identify risk factors (RFs) for SCD in patients who underwent active cancer treatment. The study population comprised 8,356 patients who received any cancer treatment at the University of Rochester Medical Center from 2011 to 2020. The primary end point was the occurrence of SCD within 6 months of cancer treatment. SCD was defined by using the modified Hinkle-Thaler classification. The mean age at the time of cancer treatment was 64 ± 14 years and 49% were women. All-cause mortality occurred in 834 patients (10%), of whom 51 (6%) were identified as SCD. The cumulative probability of SCD at 6 months was 0.6%. Age <74 years (0.042), history of congestive heart failure (0.058) and lung cancer (0.004) were identified as independent RFs for SCD in the multivariate Cox regression models. The cumulative probability of SCD at 6 months from cancer treatment initiation was significantly higher in patients with ≥2 RFs (1.6%) than in patients with 0 or 1 RF (0.5%) (log-rank p <0.001). In conclusion, our findings suggest that active cancer treatment is associated with SCD risk that is more pronounced in younger patients (< 74 years), patients with cancer and a history of heart failure, and those who underwent treatment for lung cancer. Future studies should address appropriate modalities for prevention and protection in this high-risk population.

Arrhythmogenic Cardiotoxicity Associated With Contemporary Treatments of Lymphoproliferative Disorders.

Background There are limited data on risk of arrhythmias among patients with lymphoproliferative disorders. We designed this study to determine the risk of atrial and ventricular arrhythmia during treatment of lymphoma in a real-world setting. Methods and Results The study population comprised 2064 patients included in the University of Rochester Medical Center Lymphoma Database from January 2013 to August 2019. Cardiac arrhythmias-atrial fibrillation/flutter, supraventricular tachycardia, ventricular arrhythmia, and bradyarrhythmia-were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes. Multivariate Cox regression analysis was used to assess the risk of arrhythmic events with treatments categorized as Bruton tyrosine kinase inhibitor (BTKi), mainly ibrutinib/non-BTKi treatment versus no treatment. Median age was 64 (54-72) years, and 42% were women. The overall rate of any arrhythmia at 5 years following the initiation of BTKi was (61%) compared with (18%) without treatment. Atrial fibrillation/flutter was the most common type of arrhythmia accounting for 41%. Multivariate analysis showed that BTKi treatment was associated with a 4.3-fold (P<0.001) increased risk for arrhythmic event (P<0.001) compared with no treatment, whereas non-BTKi treatment was associated with a 2-fold (P<0.001) risk increase. Among subgroups, patients without a history of prior arrhythmia exhibited a pronounced increase in the risk for the development of arrhythmogenic cardiotoxicity (3.2-fold; P<0.001). Conclusions Our study identifies a high burden of arrhythmic events after initiation of treatment, which is most pronounced among patients treated with the BTKi ibrutinib. Patients undergoing treatments for lymphoma may benefit from prospective focused cardiovascular monitoring prior, during, and after treatment regardless of arrhythmia history.

Racial differences in clinical characteristics and readmission burden among patients with a left ventricular-assist device.

BACKGROUND: There are limited data regarding racial disparities in outcomes after left ventricular assist device (LVAD) implantation. The purpose of this study was to compare clinical characteristics and the burden of readmissions by race among patients with LVAD. METHODS: The study population included 461 patients implanted with LVADs at the University of Rochester Medical Center, NY from May 2008 to March 2020. Patients were stratified by race as White patients (N = 396 [86%]) and Black patients (N = 65 [14%]). The Anderson-Gill recurrent regression analysis was used to assess the independent association between race and the total number of admissions after LVAD implant during an average follow-up of 2.45 ± 2.30 years. RESULTS: Black patients displayed significant differences in baseline clinical characteristics compared to White patients, including a younger age, a lower frequency of ischemic etiology, and a higher baseline serum creatinine. Black patients had a significantly higher burden of readmissions after LVAD implantation as compared with White patients 10 versus 7 (average number of hospitalizations per patient at 5 years of follow-up, respectively) translated into a significant 39% increased risk of recurrent readmissions after multivariate adjustment (Hazard ratio 1.39, 95% CI; 1.07-1.82, p 0.013). CONCLUSION: Black LVAD patients experience an increased burden of readmissions compared with White patients, after adjustment for baseline differences in demographics and clinical characteristics. Future studies should assess the underlying mechanisms for this increased risk including the effect of social determinants of health on the risk of readmissions in LVAD recipients.

Risk of New-Onset Atrial Fibrillation Associated With Targeted Treatment of Lymphoma.

Background: Lymphoma treatment may be associated with new-onset atrial fibrillation (AF), especially among patients treated with Bruton tyrosine kinase inhibitors (BTKi). Objectives: The authors sought to assess the risk of new-onset AF, AF risk factors, and the impact of AF on mortality in patients with lymphoma and no history of AF. Methods: The University of Rochester Medical Center Lymphoma Database was used to identify patients. The primary outcome was any AF episode identified using the International Classification of Diseases-10th Revision codes. Multivariable Cox regression was used to assess the risk of AF through the use of a time-dependent covariate for treatment overall as well as separate time-varying measures of BTKi (mainly ibrutinib) and non-BTKi treatment. The relative risk of all-cause mortality was determined using Cox proportional hazards analysis. Results: Among 1,957 lymphoma patients, the rate of AF at 5-years following initiation of BTKi treatment was higher (25%) compared to those receiving non-BTKi therapy (8%), and those receiving no treatment (4%). Multivariable analysis showed that BTKi treatment was associated with pronounced increased risk for AF compared to no treatment (HR: 5.07 [95% CI: 2.88-8.90; P < 0.001]). Non-BTKi treatment was associated with an increased risk of AF compared to no treatment (HR: 1.82 [95% CI: 1.14-2.89; P = 0.012]). Risk factors for the development of AF included age ≥64 years, male sex, hypertension, and lymphoma treatment. New AF was associated with an increased risk for subsequent mortality (HR: 3.71 [95% CI: 2.59-5.31]). Conclusions: Patients undergoing lymphoma treatment, especially those with high-risk features, may benefit from AF surveillance.

Smoking and the Risk of Stroke in Patients with a Left Ventricular Assist device.

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.

Effect of atorvastatin on lipogenic, inflammatory and thrombogenic markers in women with the metabolic syndrome.

BACKGROUND AND AIM: Specific drug therapy to target the underlying proinflammatory and prothrombotic state in patients with metabolic syndrome (MS) is lacking. We sought to study the effect of high-intensity atorvastatin on markers of lipogenesis, inflammation and thrombogenesis, in women with MS in the absence of cardiovascular disease or diabetes. METHODS AND RESULTS: This randomized double-blinded controlled trial included 88 women with MS (according to National Cholesterol Education Panel Adult Treatment Panel III criteria) and low atherosclerotic cardiovascular risk. Participants were randomized to receive atorvastatin 80 mg or matching placebo. Thrombogenic, lipogenic and inflammatory markers were collected at the time of enrollment, after a 6-week dietary run-in phase (time of randomization), and at 6- and 12-weeks after randomization. At 6 weeks post-randomization, there was significant reduction in total cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein-B (Apo-B) and Apo-B/Apo-A1 ratio in the atorvastatin arm compared to placebo. This difference persisted at 12-weeks post randomization. There was no significant difference in fasting blood glucose, high-density lipoprotein cholesterol, high sensitivity C-reactive protein, serum leptin, Apo-A1, intercellular adhesion molecule 1 and platelet activity. A significant increase in vascular adhesion molecule 1 at 6 and 12 weeks was seen within the atorvastatin arm. No difference was observed in blood pressure and waist circumference. CONCLUSIONS: In conclusion, high-intensity atorvastatin has an early and significant impact on lipoproteins and apolipoproteins but did not lower inflammatory, thrombogenic or biomarkers of platelet activity and aggregation in women with MS. The use of statins for primary prevention in these patients should be further explored.

Clinical Significance of Early Hospital Readmission in Continuous-Flow Left Ventricular Assist Device Patients.

Data on the clinical significance of early hospital readmission within 90 days following left ventricular assist device (LVAD) implantation in patients with continuous-flow LVAD are limited. We aimed to assess the incidence, predictors, and outcomes of 90-day readmission in LVAD patients. Hospital readmission or death was assessed within 90 days after hospital discharge in 177 patients with HeartMate II LVADs implanted between May 2008 and June 2014. Predictors of early readmission and risk of death were evaluated using multivariable Cox models following adjustment for clinical covariates. Hospital readmission or death rate was 37% within 90 days. Age at implantation (hazard ratio [HR] = 1.03 per 1 year increase, p = 0.016), diabetes (HR = 2.19, p = 0.031) and smoking at baseline (HR = 2.06, p = 0.034) predicted early hospital readmission, while a higher baseline body mass index was found to be protective (HR = 0.92 per each unit increase in body mass index, p = 0.003). One-year all-cause mortality was 19% in patients with early hospital readmission as compared to 1% with no early hospital readmission (HR 15.50, p = 0.01). One-year mortality was 35% in patients with 2 or more readmissions compared to 10% mortality in patients with one readmission and 1% mortality in patients with no readmissions (p < 0.001). In LVAD patients, there is a high incidence of hospital readmission within 90 days, which is associated with an increased mortality. Targeted interventions, such as closer follow-up to prevent early and recurrent hospital readmissions in LVAD recipients, are warranted to improve outcomes.

Prognostic Usefulness of Systolic Blood Pressure One-Year Following Cardiac Resynchronization Therapy (from MADIT-CRT).

Low systolic blood pressure (SBP) is associated with increased mortality and heart failure in patients with left ventricular dysfunction. Data on the relation between SBP measured following cardiac resynchronization therapy implantation and subsequent clinical events are limited. We hypothesized that assessment of systolic blood pressure at 12 months after cardiac resynchronization therapy can be used to identify patients with increased risk for adverse cardiovascular outcomes. The study population comprised 1000 patients who underwent cardiac resynchronization therapy implantation in MADIT-CRT. Outcomes were compared between patients with low (<110 mm Hg) and preserved SBP (≥110 mm Hg) at 1 year. At 1 year following cardiac resynchronization therapy, 800 patients (80%) had preserved systolic blood pressure. Kaplan-Meier survival analysis showed that the rate of heart failure or death during subsequent follow-up was significantly higher among patients with low SBP as compared with a preserved SBP at 12 months (2-year rates: 20% vs 12%, respectively; log-rank p value = 0.009 for the overall difference during follow-up). Consistently, multivariate analysis showed that patients with preserved SBP at 1 year had a 29% lower risk of HF or death when compared with the low SBP group (p = 0.024). The association between SBP measured following cardiac resynchronization therapy implantation and subsequent clinical events was more pronounced among patients with nonischemic cardiomyopathy (p value for SBP-by-HF etiology interaction = 0.034). In conclusion, assessment of SBP following cardiac resynchronization therapy can be used for improved long-term risk stratification in this population.

Risk of Ventricular Tachyarrhythmic Events in Patients Who Improved Beyond Guidelines for a Defibrillator in MADIT-CRT.

OBJECTIVES: This study assessed the arrhythmic risk of cardiac resynchronization therapy (CRT) patients who improved beyond Heart Rhythm Society/European Society of Cardiology guidelines for an implantable cardioverter-defibrillator (ICD) (ischemic cardiomyopathy: left ventricular ejection fraction [LVEF] >35% or New York Heart Association [NYHA] functional class I and if LVEF was 31% to 35%; nonischemic cardiomyopathy: LVEF >35% or NYHA functional class I and if LVEF was ≤35%). BACKGROUND: It is currently unknown whether protection with a defibrillator is still warranted in patients who respond to CRT. METHODS: This study compared the risk of ICD therapy for any ventricular tachyarrhythmia (VTA) and for fast VTA (≥200 beats/min) among patients implanted with a CRT with a defibrillator (CRT-D) in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) (N = 734) who improved at 1 year beyond guideline recommendations for primary ICD therapy (group A) with those who remained within guideline recommendations for an ICD at 1 year (group B). RESULTS: Most patients implanted with a CRT-D device improved at 1 year beyond guideline indications for an ICD (90%). Multivariate analysis showed lower risks for any VTA and fast VTA among group A patients versus group B patients (57% risk reduction; p = 0.0006 and 46% risk reduction; p = 0.068, respectively). However, the 2-year rates of any VTA and fast VTA among CRT patients who improved beyond guidelines indications for an ICD was still substantial (VTA: 13% and 29%, and fast VTA: 7% and 16%, respectively). CONCLUSIONS: Most patients with mild heart failure implanted with a CRT device experience an improvement in left ventricular function and/or NYHA functional class beyond guideline recommendations for primary ICD therapy. However, despite this pronounced CRT response, there remains a substantial VTA risk, and protection with a defibrillator may still be warranted in this population.

Implantable Cardioverter Defibrillators and Survival in Continuous-Flow Left Ventricular Assist Device Patients.

The association of an implantable cardioverter defibrillator (ICD) with survival in patients with left ventricular assist devices (LVADs) is not well understood. We evaluated all-cause mortality by the presence of an ICD at the time of LVAD implantation, or by ICD implantation after LVAD placement in 191 patients, using Kaplan-Meier survival analyses and Cox models with multivariate adjustment. During the median follow-up of 23 months, 33 of 129 patients (26%) with an ICD and 17 of 62 patients (27%) without an ICD died. Patients had similar all-cause mortality with or without an ICD before LVAD, after censoring for post-LVAD ICD implantation (log-rank p = 0.889). Multivariate models after adjustments revealed no statistically significant survival benefit from an ICD before LVAD (hazard ratio [HR]: 0.65, 95% CI: 0.27-1.57, p = 0.340). Thirty-one of 62 (50%) patients without an ICD before LVAD implantation subsequently received an ICD after LVAD, although these patients did not have significantly better survival when compared with those with no ICD in a time-dependent analysis (HR: 0.70, 95% CI: 0.25-1.95, p = 0.497). Among LVAD patients, neither a previously implanted ICD nor a new ICD implantation after LVAD yielded statistically significant survival benefit. Further studies are warranted to investigate the role of ICD implantation in LVAD patients.

Prospective analysis of bleeding events in left ventricular assist device patients.

BACKGROUND: Bleeding is a major cause of morbidity in patients with continuous flow left ventricular assist devices (LVADs). We sought to identify clinical predictors of bleeding within the first year of LVAD implantation. METHODS: A prospective study was performed on 30 patients with HeartMate II implantation at the University of Rochester Medical Center, Rochester, New York, United States. Blood was collected within 1 week before implantation, and at 1, 3, and 30 ± 10 days after implantation. Blood samples were analyzed for prothrombin time (PT), international normalized ratio (INR), von Willebrand factor (vWF) activity, vWF antigen, vWF multimers, collagen binding assay, factor VIII, and epinephrine closure time. The first bleeding event within 1 year of implantation was recorded. RESULTS: There were 17 (57%) patients with a bleeding event. The cumulative incidence of bleeding was 50% at 304 days. Age at the time of LVAD implantation was associated with higher risk of bleeding (hazard ratio (HR) = 1.05, 95% confidence interval (CI) = 1.01-1.10, p = 0.013). Higher baseline INR was also associated with increased risk of bleeding after adjusting for age at the time of implant (HR = 6.58, 95% CI = 1.21-35.70, p = 0.028). The bleeders and non-bleeders had similar hemostatic markers at all four time points. Prior to LVAD, mean epinephrine closure time was similar between bleeders and non-bleeders. However, post LVAD measurement of epinephrine, closure time was frequently limited by platelet clumping. CONCLUSION: Older age and baseline INR are associated with higher risk of bleeding in LVAD patients. Platelet clumping may suggest underlying platelet dysfunction and associated high risk of bleeding.

Influence of Diabetes Mellitus on Outcomes in Patients After Left Ventricular Assist Device Implantation.

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.

Renal Function Changes Following Left Ventricular Assist Device Implantation.

Limited data assessing the clinical significance of post-left ventricular assist device (LVAD) in renal function are available. We aimed to investigate the impact of changes in renal function after LVAD implantation on subsequent long-term outcomes. We followed 184 patients with HeartMate II LVADs implanted between May 2008 and November 2014. Serial assessment of renal function, was performed at baseline and at day 1, day 7, 1 month, 3 months, 6 months, 1 year, and 2 years after implantation. Effects of 1-month GFR and changes in GFR from baseline to 1 month on long-term mortality and hospital re-admission were evaluated. There were 30 patients with GFR <45 (low), 44 with GFR 45 to 59 (intermediate), and 110 with GFR ≥60 (normal) at baseline. Only patients with baseline GFR <45 experienced significant improvement in GFR after 2 years of follow-up (p = 0.012). At 1 month, a higher GFR category was significantly associated with a 31% reduction in mortality (hazard ratio [HR] 0.69, CI 0.49 to 0.98, p = 0.036), but not re-admission. Patients with baseline low and intermediate GFR who had no improvement in renal function category at 1 month experienced significantly greater risk of mortality (HR 1.95, CI 1.10 to 3.43, p = 0.022) and re-admission (HR 1.75, CI 1.07 to 2.84, p = 0.025), relative to patients whose GFR was normal at baseline and 1 month. In conclusion, renal function after LVAD implantation improves in patients with GFR <45. Change in renal function from baseline to 1 month after implantation is a powerful marker of long-term outcomes.

Stopping conventional showering decreases Pseudomonas infections in left ventricular assist device patients.

BACKGROUND: Left ventricular assist device (LVAD) exit-site infections represent a major challenge in the era of modern LVADs. Infections caused by Pseudomonas are particularly difficult to treat due to limited antibiotic susceptibility. We hypothesized that keeping the LVAD exit site dry while bathing could result in reduced incidence of Pseudomonas infections. METHODS: Starting in April 2013, all patients who underwent placement of HeartMate II (HM II) LVAD were instructed not to take conventional showers and to keep the exit site dry while bathing. We retrospectively reviewed patients who underwent HeartMate II LVAD implantation at our institution. Overall and Pseudomonas exit-site infections were compared between two groups: Group 1 was implanted with an LVAD prior to intervention (4/1/2013) and Group 2 after the intervention. Both groups were subjected to cumulative hazard analysis and compared using log-rank test. RESULTS: From November 2006 to September 2015, 283 patients underwent HM II LVAD placement at a single institution (Group 1, 163 patients; Group 2, 120 patients). Median age was 59 years (interquartile range [IQR] 50-65), and 57 (20%) were female. Overall, driveline infection was noted in 86 (30%) patients. Pseudomonas was the causative or coexisting organism in 16 (6%) patients. Median days to infection were 347 (IQR, 162-568). Driveline infection was identified in 69 (42%) patients in Group 1 and 17 (14 %) in Group 2. Pseudomonas was an infectious organism in 15 (9%) patients of Group 1 and one (1%) patient of Group 2. The incidence of Pseudomonas exit-site infections (p = 0.077) decreased substantially after the intervention. CONCLUSIONS: Stopping conventional showering may reduce the rate of Pseudomonas LVAD exit-site infections. Additional, multi-institutional data are needed to further evaluate these findings.

Effect of Gender on the Risk of Neurologic Events and Subsequent Outcomes in Patients With Left Ventricular Assist Devices.

Previous studies have shown that women with continuous-flow left ventricular assist devices (LVADs) are at greater risk of neurologic events. However, the relation between neurologic events and subsequent outcomes by gender is not well understood. We aimed to identify gender differences in the risk of neurologic events in patients with LVAD and the impact of time-dependent neurologic event on all-cause mortality by gender. Our study included 34 women and 157 men who received a HeartMate II LVAD at the University of Rochester Medical Center, Rochester, New York, from May 5, 2008, to June 5, 2014. Neurologic event was defined as a transient ischemic attack or cerebrovascular accident (hemorrhagic or ischemic). During a median follow-up of 25 months, 16 women (47%) and 20 men (13%) had neurologic events. Among patients with neurologic events, 7 women (44%) and 9 men (45%) died. Women had a 4.67-fold greater risk of neurologic events (hazard ratio [HR] 4.67, 95% confidence interval [CI] 2.26 to 9.66, p <0.001) compared with men. Women with neurologic events had an increased risk of all-cause mortality compared to women without neurologic event (HR 4.84, 95% CI 1.33 to 17.55, p = 0.017). Similarly, men with neurologic events had an increased risk of all-cause mortality compared to men without neurologic event (HR 4.20, 95% CI 1.93 to 9.17, p <0.001, interaction p = 0.854). In conclusion, among patients with LVAD, women are at greater risk of neurologic event compared to men. Both women and men after LVAD have similar high risk of all-cause mortality after neurologic events.

Effect of obesity on the effectiveness of cardiac resynchronization to reduce the risk of first and recurrent ventricular tachyarrhythmia events.

BACKGROUND: Obesity is associated with multiple adverse cardiovascular conditions and may increase the risk of ventricular tachyarrhythmias (VT/VF). There is limited data on the association between obesity and risk of VT/VF requiring appropriate implantable cardioverter-defibrillator (ICD) therapies and the effectiveness of cardiac resynchronization therapy (CRT) to reduce risk for VT/VF. The multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT) was design to investigate effectiveness of CRT therapy to reduce cardiovascular outcome for patients with heart failure (HF) and reduced ejection fraction. METHODS AND RESULTS: We identified patients enrolled in the MADIT CRT trial as obese (n = 433) and non-obese (n = 845) and analyzed their risk for appropriate device therapy for VT/VF, repeated VT/VF events, fast VT/VF, as well as events after first VT/VF episodes. Obesity was defined as body mass index (BMI) ≥30 kg/m(2). Among ICD patients, the risk of first appropriate ICD therapy for VT/VF at 3 years was similar between obese and non-obese patients (23 vs. 21 %, p = 0.76). CRT-D treatment reduced the risk of first appropriate ICD therapy both in non-obese ([HR]; 0.58 [CI]: 0.42-0.79; p < 0.001) and obese patients (HR 0.75, 95 % CI 0.5-1.38; p = 0.179) (interaction p value 0.323). Similarly, a significant reduction in the risk of fast VT/VF was observed in non-obese patients ([HR]; 0.49 [CI]: 0.33-0.73; p < 0.001) and obese ([HR]; 0.49 [CI]: 0.29-0.81; p < 0.01), (interaction p value 0.984). CONCLUSION: Obese and non-obese patients with mild heart failure have a similar risk of ventricular tachyarrhythmias. Obesity in mild heart failure did not diminish the clinical benefit of cardiac resynchronization therapy to reduce risk for appropriate ICD therapy. Clinical trial registration http://clinicaltrials.gov/ct2/show/NCT00180271.

Metabolic syndrome is associated with different clinical outcome after cardiac resynchronization therapy in patients with ischemic and non-ischemic cardiomyopathy.

BACKGROUND: Although association of metabolic syndrome (MS) and ischemic heart disease is strongly established, it is not known whether presence of MS may differently influence clinical responses to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the associations between obesity and metabolic features and the clinical outcome after cardiac resynchronization with defibrillator therapy (CRT-D), compared to an implantable cardioverter defibrillator (ICD). METHODS: The risk of heart failure (HF) or death and death alone was evaluated in 829 non-obese patients, 156 obese patients without MS, and 277 obese patients with MS (all with left bundle branch block), who were enrolled in the Multicenter Automatic Defibrillator Implanta-tion Trial with Cardiac Resynchronization Therapy (MADIT-CRT). RESULTS: Obese patients with MS (HR 0.50, 95% CI 0.32-0.77, p = 0.002), obese patients without MS (HR 0.57, 95% CI 0.30-1.06, p = 0.077), and non-obese patients (HR 0.48, 95% CI 0.37-0.62, p < 0.001) had a similar risk reduction of HF/death in response to CRT-D therapy when compared to ICD patients. However, among those with non-ischemic cardiomyo-pathy, obese patients with MS experienced a 90% reduction for HF/death (HR 0.11, 95% CI 0.04-0.32, p < 0.001), whereas obese patients without MS had no reduction (HR 0.98, 95% CI 0.48-1.98, p = 0.951; interaction p < 0.001). The reverse was observed in ischemic car-diomyopathy patients: obese patients with MS had no reduction in the risk of HF/death (HR 0.80, 95% CI 0.48-1.34, p = 0.402), while obese patients without MS showed a significant reduction in the risk of events (HR 0.15, 95% CI 0.04-0.65, p = 0.011; interaction p = 0.036). Similar trends were observed for the endpoint of death. CONCLUSIONS: Presence of MS differentiates the response to CRT in obese patients with is-chemic and non-ischemic etiology for HF.