Arrhythmia and Survival Outcomes Among Black Patients and White Patients With a Primary Prevention Defibrillator.

BACKGROUND: Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD). METHODS: The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM). RESULTS: Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P<0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P<0.001 for both), and a higher risk of death (HR 1.92; P=0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation. CONCLUSIONS: Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients.

Prior history of atrial fibrillation and arrhythmic outcomes: Data from the WEARIT-II prospective registry.

INTRODUCTION: Wearable cardioverter defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. METHODS: In WEARIT-II, the cumulative probability of any sustained or nonsustained VT/VF (WCD-treated and nontreated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method by prior AF, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by prior AF using negative binomial regression. RESULTS: WEARIT-II enrolled 2000 patients, 557 (28%) of whom had AF before enrollment. Cumulative probability of any sustained or nonsustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p = .001). Similarly, the recurrent rate of any sustained or nonsustained VT/VF was significantly higher in patients with prior AF versus no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p = .001). Patients with prior AF also had a significantly higher burden of any WCD-detected atrial arrhythmias/SVT/inappropriate arrhythmias therapy (183.2 events per 100 patient-years vs. 74.8 events per 100 patient-years, p < .001). CONCLUSION: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.

Association of device detected atrial and ventricular tachyarrhythmia with adverse events in patients with an implantable cardioverter-defibrillator.

INTRODUCTION: Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death. METHODS: The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment. Multivariate cox analysis was performed to evaluate the time-dependent association between development of in-trial device detected AF and VT/VF with subsequent CHF exacerbation and death. RESULTS: Multivariate analysis showed that AF occurrence and VT/VF occurrence were both associated with a similar magnitude of risk for subsequent CHF exacerbation (HR = 1.73 and 1.87 respectively, p < .001 for both). In contrast, only in-trial VT/VF was associated with a significant > two-fold increase in the risk of subsequent mortality (HR = 2.13, p < .001) whereas AF occurrence was not associated with a significant mortality increase after adjustment for in-trial VT/VF (HR = 1.36, p = .096). CONCLUSION: Our findings from a large cohort of ICD recipients enrolled in landmark clinical trials show that device detected AF and VT/VF can be used to identify patients with increased risk for CHF exacerbation and mortality. These findings suggest a need for early intervention in CHF patients who develop device-detected atrial and ventricular tachyarrhythmias.

Effect of sodium glucose cotransporter 2 inhibitors on atrial tachy-arrhythmia burden in patients with cardiac implantable electronic devices.

INTRODUCTION: Use of sodium glucose cotransporter 2 inhibitors (SGLT2i) was associated with a reduction in atrial fibrillation hospitalizations. Therefore, we aim to evaluate the effects of SGLT2i on atrial tachy-arrhythmias (ATA) in patients with cardiac implantable electronic devices (CIEDs). METHODS: All 13 888 consecutive patients implanted with a CIED in two tertiary medical centers were enrolled. Treatment with SGLT2i was assessed as a time dependent variable. The primary endpoint was the total number of ATA. Secondary endpoints included total number of ventricular tachy-arrhythmias (VTA), ATA and VTA, and death. All events were independently adjudicated blinded to the treatment. Multivariable propensity score modeling was performed. RESULTS: During a total follow-up of 24 442 patient years there were 62 725 ATA and 10 324 VTA events. Use of SGLT2i (N = 696) was independently associated with a significant 22% reduction in the risk of ATA (hazard ratio [HR] = 0.78 [95% confidence interval {CI} = 0.70-0.87]; p < .001); 22% reduction in the risk of ATA/VTA (HR = 0.78 [95% CI = 0.71-0.85]; p < .001); and with a 35% reduction in the risk of all-cause mortality (HR = 0.65 [95% CI = 0.45-0.92]; p = .015), but was not significantly associated with VTA risk (HR = 0.92 [95% CI = 0.80-1.06]; p = .26). SGLT2i were associated with a lower ATA burden in heart failure (HF) patients but not among diabetes patients (HF: HR = 0.68, 95% CI = 0.58-0.80, p < .001 vs. Diabetes: HR = 0.95, 95% CI = 0.86-1.05, p = .29; p < .001 for interaction between SGLT2i indication and ATA burden). CONCLUSION: Our real world findings suggest that in CIED HF patients, those with SGLT2i had a pronounced reduction in ATA burden and all-cause mortality when compared with those not on SGLT2i.

Genetic variant annotation scores in congenital long QT syndrome.

BACKGROUND: Congenital Long QT Syndrome (LQTS) is a hereditary arrhythmic disorder. We aimed to assess the performance of current genetic variant annotation scores among LQTS patients and their predictive impact. METHODS: We evaluated 2025 patients with unique mutations for LQT1-LQT3. A patient-specific score was calculated for each of four established genetic variant annotation algorithms: CADD, SIFT, REVEL, and PolyPhen-2. The scores were tested for the identification of LQTS and their predictive performance for cardiac events (CE) and life-threatening events (LTE) and then compared with the predictive performance of LQTS categorization based on mutation location/function. Score performance was tested using Harrell's C-index. RESULTS: A total of 917 subjects were classified as LQT1, 838 as LQT2, and 270 as LQT3. The identification of a pathogenic variant occurred in 99% with CADD, 92% with SIFT, 100% with REVEL, and 86% with PolyPhen-2. However, none of the genetic scores correlated with the risk of CE (Harrell's C-index: CADD = 0.50, SIFT = 0.51, REVEL = 0.50, and PolyPhen-2 = 0.52) or LTE (Harrell's C-index: CADD = 0.50, SIFT = 0.53, REVEL = 0.54, and PolyPhen-2 = 0.52). In contrast, high-risk mutation categorization based on location/function was a powerful independent predictor of CE (HR = 1.88; p < .001) and LTE (HR = 1.89, p < .001). CONCLUSION: In congenital LQTS patients, well-established algorithms (CADD, SIFT, REVEL, and PolyPhen-2) were able to identify the majority of the causal variants as pathogenic. However, the scores did not predict clinical outcomes. These results indicate that mutation location/functional assays are essential for accurate interpretation of the risk associated with LQTS mutations.

Confirm Rx insertable cardiac monitor for primary atrial fibrillation detection in high-risk heart failure patients (Confirm-AF trial).

BACKGROUND: Patients with heart failure (HF) represent a large population of patients who are at high risk for complications related to undiagnosed atrial fibrillation (AF). However, currently there are limited modalities available for early AF detection in this high-risk population. An implantable cardiac monitor (ICM) is inserted subcutaneously and can provide long-term arrhythmia information via remote monitoring. METHODS AND RESULTS: Confirm-AF is a prospective randomized, nonblinded, two arm, multicenter clinical trial to be performed in the United States, enrolling 477 patients with a history of HF hospitalization and left ventricular ejection fraction >35% from 30 medical sites. Patients will be randomized in a 2:1 fashion to undergo ICM implant with remote monitoring and symptom-triggered mobile app transmissions versus (vs.) Non-ICM management and follow-up. The primary objective of this trial is to compare the time to first detection of AF lasting > 5 min using an Abbott ICM compared to non-ICM monitoring in symptomatic HF patients. This article describes the design and analytic plan for the Confirm-AF trial. CONCLUSIONS: The Confirm-AF trial seeks to accurately define the burden of AF in high-risk HF patients with LVEF > 35% using an Abbott ICM. A finding showing significantly higher incidence of AF along with improved clinical outcomes with ICM monitoring is expected to have substantial clinical implications and may change the method of monitoring high-risk HF patients.

Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial.

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

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.

Outcomes associated with the high sensitivity cardiac troponin testing in patients presenting with non-cardiovascular disorders.

There are limited data regarding the utility of troponin testing in patients presenting with non-cardiovascular (CV) symptoms as the primary manifestation. The study population comprised 2057 patients who presented to the emergency department (ED) of a US healthcare system with non-CV symptoms as the primary manifestation between January and September 2018. We compared the effect of high-sensitivity cardiac troponin T (hs-cTnT) (n = 901) after its introduction vs. 4th generation cTnT (n = 1156) on the following outcomes measures: ED length of stay (LOS), coronary tests/procedures (angiography or stress test), and long-term mortality. Mean age was 64 ± 17 yrs., and 47% were female. Primary non-CV manifestations included pneumonia, obstructive pulmonary disease, infection, abdominal-complaint, and renal failure. Mean follow up was 9 ± 4 months. Patients' demographics and medical history were clinically similar between the two troponin groups. A second cTn test was obtained more frequently in the hs-cTnT than cTnT (84% vs. 32%; p < 0.001), possibly leading to a longer ED stay (8.1 ± 8.2 h vs 5.6 ± 3.4 h, respectively; p < 0.001). Coronary tests/procedures were performed at a significantly higher rate in the hs-cTnT than cTnT following the introduction of the hs-cTnT test (28% vs. 22%, p < 0.001). Multivariate analysis showed that following the introduction of hs-cTnT testing, there was a significant 27% lower risk of long-term mortality from ED admission through follow-up (HR = 0.73, 95%CI 0.54-0.98; p = 0.035). In conclusion, we show that in patients presenting primarily with non-CV disorders, the implementation of the hs-cTnT was associated with a higher rate of diagnostic coronary procedures/interventions, possibly leading to improved long-term survival rates.

Left atrial appendage exclusion with less invasive left ventricular assist device implantation.

OBJECTIVES: The objective of this single-center, pilot, prospective, and historical control study is to evaluate safety and feasibility outcomes associated with left atrial appendage exclusion (LAAE) concomitant with left ventricular assist device (LVAD) implantation via less invasive surgery (LIS) as a stroke prevention strategy. METHODS: A predefined number of 30 eligible subjects scheduled for LIS LVAD with LAAE were enrolled in the prospective arm between January 2020 and February 2021. Eligible retrospective LIS LVAD patients without LAAE were propensity-matched in a 1:1 ratio with the prospective arm subjects. The primary study objectives were to evaluate the safety, feasibility, and efficacy of the LAAE concomitant with LIS LVAD. RESULTS: Preoperative characteristics of patients in the Non-LAAE and LAAE groups were similar. LAAE was successfully excluded in all prospective patients (100%). Primary safety endpoints of chest tube output within the first 24 postoperative hours, Reoperation for bleeding within 48 h, and index hospitalization mortality demonstrated comparable safety of LAAE versus Non-LAAE with LIS LVAD. Cox proportional hazard regression demonstrated that LAAE with LIS LVAD was associated with 37% and 49% reduction in the risk of stroke and disabling stroke, respectively (p > .05). CONCLUSION: Results from our pilot study demonstrated the safety and feasibility of LAAE concomitant with LIS LVAD as a stroke prevention strategy. This is the first prospective study describing LAAE performed concomitantly to less invasive LVAD implantation. The efficacy of LAAE in long-term stroke prevention needs to be confirmed in future prospective randomized clinical trials.

Impact of surgical approach for left ventricular assist device implantation on postoperative invasive hemodynamics and right ventricular failure.

BACKGROUND: Right ventricular failure (RVF) remains one of the major causes of morbidity and mortality after left ventricular assist device (LVAD) implantation. We sought to compare immediate postoperative invasive hemodynamics and the risk of RVF following two different surgical approaches: less invasive surgery (LIS) versus full sternotomy (FS). METHODS: The study population comprised all 231 patients who underwent implantation of a HeartMate 3 (Abbott) LVAD at our institution from 2015 to 2020, utilizing an LIS (n = 161; 70%) versus FS (n = 70; 30%) surgical approach. Outcomes included postoperative invasive hemodynamic parameters, vasoactive-inotropic score (VIS), RVF during index hospitalization, and 6-month mortality. RESULTS: Baseline clinical characteristics of the two groups were similar. Multivariate analysis showed that LIS, compared with FS, was associated with the improved cardiac index (CI) at the sixth postoperative hour (p = .036) and similar CI at 24 h, maintained by lower VIS at both timepoints (p = .002). The LIS versus FS approach was also associated with a three-fold lower incidence of in-hospital severe RVF (8.7% vs. 28.6%, p < .001) and need for RVAD support (5.0% vs. 17.1%, p = .003), and with 68% reduction in the risk of 6-month mortality after LVAD implantation (Hazard ratio, 0.32; CI, 0.13-0.78; p = .012). CONCLUSION: Our findings suggest that LIS, compared with FS, is associated with a more favorable hemodynamic profile, as indicated by similar hemodynamic parameters maintained by lower vasoactive-inotropic support during the acute postoperative period. These findings were followed by a reduction in the risk of severe RVF and 6-month mortality in the LIS group.

Predicted benefit of an implantable cardioverter-defibrillator: the MADIT-ICD benefit score.

AIMS: The benefit of prophylactic implantable cardioverter-defibrillator (ICD) is not uniform due to differences in the risk of life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) and non-arrhythmic mortality. We aimed to develop an ICD benefit prediction score that integrates the competing risks. METHODS AND RESULTS: The study population comprised all 4531 patients enrolled in the MADIT trials. Best-subsets Fine and Gray regression analysis was used to develop prognostic models for VT (≥200 b.p.m.)/VF vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF). Eight predictors of VT/VF (male, age < 75 years, prior non-sustained VT, heart rate > 75 b.p.m., systolic blood pressure < 140 mmHg, ejection fraction ≤ 25%, myocardial infarction, and atrialarrhythmia) and 7 predictors of non-arrhythmic mortality (age ≥ 75 years, diabetes mellitus, body mass index < 23 kg/m2, ejection fraction ≤ 25%, New York Heart Association ≥II, ICD vs. cardiac resynchronization therapy with defibrillator, and atrial arrhythmia) were identified. The two scores were combined to create three MADIT-ICD benefit groups. In the highest benefit group, the 3-year predicted risk of VT/VF was three-fold higher than the risk of non-arrhythmic mortality (20% vs. 7%, P < 0.001). In the intermediate benefit group, the difference in the corresponding predicted risks was attenuated (15% vs. 9%, P < 0.01). In the lowest benefit group, the 3-year predicted risk of VT/VF was similar to the risk of non-arrhythmic mortality (11% vs. 12%, P = 0.41). A personalized ICD benefit score was developed based on the distribution of the two competing risks scores in the study population (https://is.gd/madit). Internal and external validation confirmed model stability. CONCLUSIONS: We propose the novel MADIT-ICD benefit score that predicts the likelihood of prophylactic ICD benefit through personalized assessment of the risk of VT/VF weighed against the risk of non-arrhythmic mortality.

Outcomes Associated with Introduction of the 5th Generation High-Sensitivity Cardiac Troponin in Patients Presenting with Cardiovascular Disorders.

BACKGROUND: The new high-sensitivity cardiac troponin T (hs-cTnT) is now widely used in the United States. OBJECTIVES: We aimed to examine outcomes associated with the introduction of the new 5th generation hs-cTnT assay among patients presenting to the emergency department (ED) with cardiovascular (CV) disorders. METHODS: The 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). RESULTS: 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%; p < 0.01), 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; p < 0.05 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]). CONCLUSIONS: 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.

Risk factors for ventricular tachyarrhythmic events in patients without left bundle branch block who receive cardiac resynchronization therapy.

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 <20%, prior nonsustained VT, and female gender. Among CRT-D patients, 114 (53%) had no RF, while 101 (47%) had ≥1 RF. The 4-year cumulative probability of VTA was higher among those with ≥1 RF compared with those without RF (40% vs. 14%, p < .001). Multivariate analysis showed that in patients without RF, treatment with CRT-D was associated with a 61% reduction in VTA compared with ICD-only therapy (p = .002), whereas among patients with ≥1 RF, treatment with CRT-D was associated with a corresponding 73% (p = .025) risk increase. Consistent results were observed when the secondary end points of VTA/death and appropriate ICD shocks were assessed. CONCLUSION: Combined assessment of factors associated with increased risk for VTA can be used for improved selection of non-LBBB patients for CRT-D.

The role and outcomes of new supraventricular tachycardia among patients with mild heart failure.

INTRODUCTION: 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. METHODS AND RESULTS: 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) Low <10, (b) Intermediate ≥10 but <20, 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 a >4-fold increased risk for VTEs (HR = 4.3; 95% CI: 1.6-11.7; P = .004) and with a >6-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). CONCLUSIONS: 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.

Competing risk analysis of ventricular arrhythmia events in heart failure patients with moderately compromised renal dysfunction.

AIMS: Patients with impaired renal function were shown to have an attenuated benefit from implantable cardioverter-defibrillator. However, there are limited data on the competing risk of ventricular arrhythmia events and death by renal function in patients without severe disease. Therefore, we aimed to assess the competing risk of ventricular arrhythmia events and death by renal function. METHODS AND RESULTS: We analysed 1782 patients (99%) enrolled in Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) with glomerular filtration rate (GFR) data available. Cumulative incidence function curves were used to display the rate of ventricular tachycardia (VT), ventricular fibrillation (VF), and the competing risk of death without experiencing VT/VF. Multivariable Fine and Gray regression models and recurrent event analysis were performed. There were 355 (20%) patients with GFR < 52 and 1427 with GFR ≥ 52 (lowest quintile). The incidence of non-fatal VT/VF at 4 years was higher in patients with high GFR (26%) as compared to low GFR (16%), whereas rates of death without non-fatal VT/VF were 5% and 20% (P < 0.001). In Fine and Gray models, the low GFR group was 35% less likely to experience VT/VF compared to the high GFR [95% confidence interval (CI) 0.48-0.88, P = 0.005]. In contrast,death without experiencing VT/VF was 3.5-fold higher in the low GFR group (95% CI 2.38-5.12, P-value < 0.001). Recurrent event analysis consistently showed a lower risk of recurrent VT/VF, recurrent anti-tachycardia pacing only, and shock in the low GFR group. CONCLUSIONS: We show, in a competing risk model, a lower risk of VT/VF events and a higher risk of mortality without an arrhythmic event in patients with moderate renal dysfunction in MADIT-CRT. These findings can be used for improved selection of patients for defibrillator therapy among CRT candidates. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00180271.

Relation between resting heart rate and the risk of ventricular tachyarrhythmias in MADIT-RIT.

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

Circadian variation and seasonal distribution of implantable defibrillator detected new onset atrial fibrillation.

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 < .01). Detection of AF during the spring and winter seasons accounted for 67% of all new device-detected AF. CONCLUSIONS: There is diurnal and seasonal variation in new onset AF. A double peak in the incidence of AF is observed during the afternoon and evening hours, and during the spring and winter seasons. This information may be useful when deciding when to screen at-risk patients for new AF.

Need for pacing in patients who qualify for an implantable cardioverter-defibrillator: Clinical implications for the subcutaneous ICD.

BACKGROUND: Implantation of the subcutaneous implantable cardioverter-defibrillator (S-ICD) is spreading and has been shown to be safe and effective; however, it does not provide brady-pacing. Currently, data on the need for brady-pacing and cardiac resynchronization therapy (CRT) implantation in patients with ICD indication are limited. METHODS: The Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II enrolled post-MI patients with reduced ejection fraction (EF ≤ 35%), randomized to either an implantable cardioverter-defibrillator (ICD) or conventional medical therapy. Kaplan-Meier analyses and multivariate Cox models were performed to assess the incidence and predictors of pacemaker (PM), or CRT implantation in the conventional arm of MADIT-II, after excluding 32 patients (6.5%) with a previously implanted PM. RESULTS: During the median follow-up of 20 months, 24 of 458 patients (5.2%) were implanted with a PM or a CRT (19 PM, 5 CRT). Symptomatic sinus bradycardia was the primary indication for PM implantation (n = 9, 37%), followed by AV block (n = 5, 21%), tachy-brady syndrome (n = 4, 17%), and carotid sinus hypersensitivity (n = 1, 4%). Baseline PR interval >200 ms (HR = 3.07, 95% CI: 1.24-7.57, p = .02), and CABG before enrollment (HR = 6.88, 95% CI: 1.58-29.84, p = .01) predicted subsequent PM/CRT implantation. Patients with PM/CRT implantation had a significantly higher risk for heart failure (HR = 2.67, 95% CI = 1.38-5.14, p = .003), but no increased mortality risk (HR = 1.06, 95% CI = 0.46-2.46, p = .89). CONCLUSION: The short-term need for ventricular pacing or CRT implantation in patients with MADIT-II ICD indication was low, especially in those with a normal baseline PR interval, and such patients are appropriate candidates for the subcutaneous ICD.

Quantitative T-wave morphology assessment from surface ECG is linked with cardiac events risk in genotype-positive KCNH2 mutation carriers with normal QTc values.

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 <470 ms in women (n = 113, age 42 ± 16 years, 43% male) were compared with genotype-negative family members (n = 1007). The TwVM was calculated using T-wave amplitudes in leads V6, II, and V2 as the square root of (TV62 + TII2 + (0.5*TV2)2 ). Cox regression analysis adjusted for gender and time-dependent beta-blocker use was performed to assess cardiac event (CE) risk, defined as syncope, aborted cardiac arrest, implantable cardioverter-defibrillator therapy, or sudden death. RESULTS: Dichotomized by median of 0.30 mV, lower TwVM was associated with elevated CE risk compared to those with high TwVM (HR = 2.95, 95% CI, 1.25-6.98, P = .014) and also remained significant after including sex and time-dependent beta-blocker usage in the Cox regression analysis (HR = 2.64, 95% CI, 1.64-4.24, P < .001). However, these associations were found only in women but not in men who had low event rates. CONCLUSION: T-wave morphology quantified as repolarization vector magnitude using T-wave amplitudes retrieved from standard 12-lead electrocardiogram predicts cardiac events risk in LQT2 women and appears useful for risk stratification of KCNH2-mutation carriers without QTc prolongation.