Yitschak Biton

Use of the Wearable Cardioverter Defibrillator in High-Risk Cardiac Patients: Data from the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II Registry)

Background— Prospective data on the safety and efficacy of the wearable cardioverter defibrillator (WCD) in a real-world setting are lacking. The Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II) Registry was designed to provide real-world data on the WCD as a strategy during a period of risk stratification. Methods and Results— The WEARIT-II Registry enrolled 2000 patients with ischemic (n=805, 40%), or nonischemic cardiomyopathy (n=927, 46%), or congenital/inherited heart disease (n=268) prescribed WCD between August 2011 and February 2014. Clinical data, arrhythmia events, implantable cardioverter defibrillator implantation, and improvement in ejection fraction were captured. The median age was 62 years; the median ejection fraction was 25%. The median WCD wear time was 90 days, with median daily use of 22.5 hours. There was a total of 120 sustained ventricular tachyarrhythmias in 41 patients, of whom 54% received appropriate WCD shock. Only 10 patients (0.5%) received inappropriate WCD therapy. The rate of sustained ventricular tachyarrhythmias by 3 months was 3% among patients with ischemic cardiomyopathy and congenital/inherited heart disease, and 1% among nonischemic patients (P=0.02). At the end of WCD use, 840 patients (42%) were implanted with an implantable cardioverter defibrillator. The most frequent reason not to implant an implantable cardioverter defibrillator following WCD use was improvement in ejection fraction. Conclusions— The WEARIT-II Registry demonstrates a high rate of sustained ventricular tachyarrhythmias at 3 months in at-risk patients who are not eligible for an implantable cardioverter defibrillator, and suggests that the WCD can be safely used to protect patients during this period of risk assessment.

Sex Differences in Long‐Term Outcomes With Cardiac Resynchronization Therapy in Mild Heart Failure Patients With Left Bundle Branch Block

Background Previous studies have shown conflicting results regarding the benefit of cardiac resynchronization therapy (CRT) by sex and QRS duration. Methods and Results In the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), we evaluated long-term clinical outcome of heart failure (HF) or death, death, and HF alone by sex and QRS duration (dichotomized at 150 ms) in left bundle-branch block patients with CRT with defibrillator backup (CRT-D) versus implantable cardioverter-defibrillator (ICD) only. There were 394 women (31%) and 887 men with left bundle-branch block. During the median follow-up of 5.6 years, women derived greater clinical benefit from CRT-D compared with implantable cardioverter-defibrillator only, with a significant 71% reduction in HF or death (hazard ratio [HR] 0.29, P<0.001) and a 77% reduction in HF alone (HR 0.23, P<0.001) compared with men, who had a 41% reduction in HF or death (HR 0.59, P<0.001) and a 50% reduction in HF alone (HR 0.50, P<0.001) (all sex-by-treatment interaction P<0.05). Men and women had similar reduction in long-term mortality with CRT-D versus implantable cardioverter-defibrillator only (men: HR 0.70, P=0.03; women: HR 0.59, P=0.04). The incremental benefit of CRT-D in women for HF or death and HF alone was consistent with QRS <150 or >150 ms. Conclusions During long-term follow-up of mild HF patients with left ventricular dysfunction and wide QRS, both women and men with left bundle-branch block derived sustained benefit from CRT-D versus implantable cardioverter-defibrillator only, with significant reduction in HF or death, HF alone, and all-cause mortality regardless of QRS duration. There is an incremental benefit with CRT-D in women for the end points of HF or death and HF alone. Clinical Trial Registration URL: https://clinicaltrials.gov/. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.

Long-Term Outcomes With Cardiac Resynchronization Therapy in Patients With Mild Heart Failure With Moderate Renal Dysfunction

Background—We aimed to determine the impact of renal function on long-term outcomes with cardiac resynchronization therapy with defibrillator among patients with mild heart failure (HF). Methods and Results—We stratified 1820 Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy patients by QRS morphology into those with and without left bundle-branch block. Subgroups within each QRS morphology category were created based on glomerular filtration rate (GFR): GFR <60 and ≥60 mL/min per 1.73 m2. Primary end point was death; secondary end points were HF/death and HF events alone during long-term follow-up. Among 1274 left bundle-branch block patients, 413 (32%) presented with GFR <60 (mean, 48.1±8.3) mL/min per 1.73 m2. Relative to the 861 (68%) patients with GFR ≥60 (mean, 79.6±16.0) mL/min per 1.73 m2, low-GFR patients experienced higher risk of death (hazard ratio [HR], 2.09; 95% confidence interval [CI], 1.53–2.86; P<0.01) and HF/death (HR, 1.46; 95% CI, 1.17–1.82; P<0.01). In both GFR groups, cardiac resynchronization therapy with defibrillator was associated with reduction in death (GFR <60: HR, 0.66; 95% CI, 0.44–1.00; P=0.05 and GFR ≥60: HR, 0.68; 95% CI, 0.44–1.05; P=0.08) and HF/death (GFR <60: HR, 0.49; 95% CI, 0.36–0.67; P<0.01 and GFR ≥60: HR, 0.50; 95% CI, 0.38–0.66; P<0.01). In the low-GFR group, there was greater absolute reduction in risk of death (GFR <60: 14% and GFR ≥60: 6%) and HF/death (GFR <60: 25 and GFR ≥60: 15%). Among non–left bundle-branch block patients, low GFR predicted outcomes; however, no benefit from cardiac resynchronization therapy with defibrillator was observed. Conclusions—In patients with mild HF, moderate renal dysfunction is associated with higher risk of death and HF during long-term follow-up. Patients with left bundle-branch block, regardless of baseline renal function, derive long-term benefit from cardiac resynchronization therapy with defibrillator, with greater absolute risk reduction in death and HF among those with moderate renal dysfunction. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.

Relationship between age and inappropriate implantable cardioverter-defibrillator therapy in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy)☆

BACKGROUND There is limited data regarding the relationship between age and inappropriate therapy among patients with an implantable cardioverter-defibrillator (ICD) and resynchronization therapy. OBJECTIVES We aimed to investigate this relationship and the effect of ICD programming on inappropriate therapy by age. METHODS In the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) 1500 patients were randomized to 3 ICD programming arms: (A) conventional with ventricular tachycardia (VT) therapy ≥170; (B) high-rate cutoff with VT therapy ≥200, and (C) prolonged 60-second delay for VT therapy ≥170. We investigated the relationship between age, the risk of inappropriate ICD therapy (including antitachycardia pacing [ATP] or shock), and ICD programming. RESULTS Cumulative incidence function Kaplan-Meier graphs showed an inverse relationship between increasing quartiles of age (Q1: ≤55, Q2: 56-64, Q3: 65-71, and Q4: ≥72 years) and the risk for inappropriate therapy. Multivariate analyses showed that each increasing decade of life was associated with 34% (P < .001), 27% (P < .001), and 26% (P < .001) reduction in the risk of inappropriate shock, inappropriate ATP, and any inappropriate therapy, respectively. Treatment arms B and C as compared with arm A were associated with a significant reduction in the risk of inappropriate therapies across all age quartiles (P < .001 for all). CONCLUSIONS Among patients with a primary prevention indication for an ICD, there is an inverse relationship between age and inappropriate ICD therapy. Innovative ICD programming of high-rate cutoff or prolonged delay for VT therapy is associated with significant reductions in inappropriate therapy among all age groups.

Long-Term Outcomes with Cardiac Resynchronization Therapy in Mild Heart Failure Patients with Moderate Renal Dysfunction

Background—We aimed to determine the impact of renal function on long-term outcomes with cardiac resynchronization therapy with defibrillator among patients with mild heart failure (HF). Methods and Results—We stratified 1820 Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy patients by QRS morphology into those with and without left bundle-branch block. Subgroups within each QRS morphology category were created based on glomerular filtration rate (GFR): GFR <60 and ≥60 mL/min per 1.73 m2. Primary end point was death; secondary end points were HF/death and HF events alone during long-term follow-up. Among 1274 left bundle-branch block patients, 413 (32%) presented with GFR <60 (mean, 48.1±8.3) mL/min per 1.73 m2. Relative to the 861 (68%) patients with GFR ≥60 (mean, 79.6±16.0) mL/min per 1.73 m2, low-GFR patients experienced higher risk of death (hazard ratio [HR], 2.09; 95% confidence interval [CI], 1.53–2.86; P<0.01) and HF/death (HR, 1.46; 95% CI, 1.17–1.82; P<0.01). In both GFR groups, cardiac resynchronization therapy with defibrillator was associated with reduction in death (GFR <60: HR, 0.66; 95% CI, 0.44–1.00; P=0.05 and GFR ≥60: HR, 0.68; 95% CI, 0.44–1.05; P=0.08) and HF/death (GFR <60: HR, 0.49; 95% CI, 0.36–0.67; P<0.01 and GFR ≥60: HR, 0.50; 95% CI, 0.38–0.66; P<0.01). In the low-GFR group, there was greater absolute reduction in risk of death (GFR <60: 14% and GFR ≥60: 6%) and HF/death (GFR <60: 25 and GFR ≥60: 15%). Among non–left bundle-branch block patients, low GFR predicted outcomes; however, no benefit from cardiac resynchronization therapy with defibrillator was observed. Conclusions—In patients with mild HF, moderate renal dysfunction is associated with higher risk of death and HF during long-term follow-up. Patients with left bundle-branch block, regardless of baseline renal function, derive long-term benefit from cardiac resynchronization therapy with defibrillator, with greater absolute risk reduction in death and HF among those with moderate renal dysfunction. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.

Relation of QRS Duration to Clinical Benefit of Cardiac Resynchronization Therapy in Mild Heart Failure Patients Without Left Bundle Branch Block: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy Substudy.

Background— There are conflicting data regarding the efficacy of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and without left bundle branch block. Methods and Results— We evaluated the long-term clinical outcomes of 537 non–left bundle branch block patients with mild HF enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study by QRS duration or morphology further stratified by PR interval. At 7 years of follow-up, the cumulative probability of HF hospitalization or death was 45% versus 56% among patients randomized to implantable cardioverter–defibrillator and CRT with defibrillator (CRT-D), respectively ( P =0.209). Multivariable-adjusted subgroup analysis by QRS duration showed that patients from the lower quartile QRS duration group (≤134 ms) experienced 2.4-fold ( P =0.015) increased risk for HF hospitalization or death with CRT-D versus implantable cardioverter–defibrillator only therapy, whereas the effect of CRT-D in patients from the upper quartiles group (QRS>134 ms) was neutral (hazard ratio [HR] =0.97, P =0.86; P value for interaction =0.024). In a second analysis incorporating PR interval, patients with prolonged QRS (>134 ms) and prolonged PR (>230 ms) were protected with CRT-D (HR=0.31, P =0.003), whereas the association was neutral with prolonged QRS (>134 ms) and shorter PR (≤230 ms;, HR=1.19, P =0.386; P value for interaction =0.002). The effect was neutral, regardless of morphology, right bundle branch block (HR=1.01, P =0.975), and intraventricular conduction delay (HR=1.31, P =0.172). Conclusions— Overall, patients with mild HF but without left bundle branch block morphology did not derive clinical benefit with CRT-D during long-term follow-up. Relatively shorter QRS was associated with a significantly increased risk with CRT-D relative to implantable cardioverter–defibrillator -only. Clinical Trial Registration— URL: . Unique identifiers: [NCT00180271][1], [NCT01294449][2], and [NCT02060110][3]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcirchf%2F9%2F2%2Fe002667.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01294449&atom=%2Fcirchf%2F9%2F2%2Fe002667.atom [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02060110&atom=%2Fcirchf%2F9%2F2%2Fe002667.atomBackground—There are conflicting data regarding the efficacy of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and without left bundle branch block. Methods and Results—We evaluated the long-term clinical outcomes of 537 non–left bundle branch block patients with mild HF enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) study by QRS duration or morphology further stratified by PR interval. At 7 years of follow-up, the cumulative probability of HF hospitalization or death was 45% versus 56% among patients randomized to implantable cardioverter–defibrillator and CRT with defibrillator (CRT-D), respectively (P=0.209). Multivariable-adjusted subgroup analysis by QRS duration showed that patients from the lower quartile QRS duration group (⩽134 ms) experienced 2.4-fold (P=0.015) increased risk for HF hospitalization or death with CRT-D versus implantable cardioverter–defibrillator only therapy, whereas the effect of CRT-D in patients from the upper quartiles group (QRS>134 ms) was neutral (hazard ratio [HR] =0.97, P=0.86; P value for interaction =0.024). In a second analysis incorporating PR interval, patients with prolonged QRS (>134 ms) and prolonged PR (>230 ms) were protected with CRT-D (HR=0.31, P=0.003), whereas the association was neutral with prolonged QRS (>134 ms) and shorter PR (⩽230 ms;, HR=1.19, P=0.386; P value for interaction =0.002). The effect was neutral, regardless of morphology, right bundle branch block (HR=1.01, P=0.975), and intraventricular conduction delay (HR=1.31, P=0.172). Conclusions—Overall, patients with mild HF but without left bundle branch block morphology did not derive clinical benefit with CRT-D during long-term follow-up. Relatively shorter QRS was associated with a significantly increased risk with CRT-D relative to implantable cardioverter–defibrillator -only. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.

Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients With Mild Heart Failure A Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Long-Term Follow-Up Substudy

Background —Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with LV dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase Systolic Blood Pressure (SBP). We therefore hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. Methods and Results —The independent contribution of SBP to outcome was analyzed in 1,267 patients with LBBB enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death, and CRT-D vs. ICD benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the ICD arm, each 10 mmHg decrement of SBP was independently associated with a significant 21% (p 2-fold risk-increase. CRT-D therapy provided the greatest HF or mortality risk reduction in patients with SBP SBP≥136 mmHg and HR=0.94, p=0.808 with SBP>136 mmHg (p for trend=0.001). Conclusions —In patients with mild HF, prolonged QRS, and LBBB, low SBP is related to higher risk of mortality or HF with ICD therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline systolic blood pressure values. Clinical Trial Registration —URL: http://www.clinicaltrials.gov. Unique identifier: [NCT00180271][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcirchf%2Fearly%2F2015%2F07%2F15%2FCIRCHEARTFAILURE.115.002208.atomBackground—Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. Methods and Results—The independent contribution of SBP to outcome was analyzed in 1267 patients with left bundle brunch block enrolled in Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death and CRT with defibrillator versus implantable cardioverter defibrillator benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the implantable cardioverter defibrillator arm, each 10-mm Hg decrement of SBP was independently associated with a significant 21% (P<0.001) increased risk for HF or death, and patients with lower quintile SBP (<110 mm Hg) experienced a corresponding >2-fold risk-increase. CRT with defibrillator provided the greatest HF or mortality risk reduction in patients with SBP<110 mm Hg hazard ratio of 0.34, P<0.001, when compared with hazard ratio of 0.52, P<0.001, in those with 110>SBP≥136 mm Hg and hazard ratio of 0.94, P=0.808, with SBP>136 mm Hg (P for trend=0.001). Conclusions—In patients with mild HF, prolonged QRS, and left bundle brunch block, low SBP is related to higher risk of mortality or HF with implantable cardioverter defibrillator therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline SBP values. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Study of the wearable cardioverter defibrillator in advanced heart‐failure patients (SWIFT)

The wearable cardioverter defibrillator (WCD) may allow stabilization until reassessment for an implantable cardioverter defibrillator (ICD) among high‐risk heart failure (HF) patients. However, there are limited data on the WCD benefit in the acute decompensated HF setting.

Roles and indications for use of implantable defibrillator and resynchronization therapy in the prevention of sudden cardiac death in heart failure.

AbstractImplantable devices are indicated in the primary and secondary prevention of potentially life-threatening ventricular tachyarrhythmias in patients with heart failure. Early studies, including the landmark MADIT trials, showed that implantable cardioverter–defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices can play a significant role in aborting and preventing ventricular arrhythmias, respectively, that can cause sudden cardiac death. To this day, there have been a number of randomized controlled trials, with respective substudy analyses, that have attempted to better understand the indications for these interventions in patient care. Here, we summarize the major results of these studies, and we discuss the role of ICD therapy for both ischemic and non-ischemic cardiomyopathy, emerging evidence in support of wearable defibrillators, and the impact of modified ICD programming strategies on patient outcomes. Regarding CRT therapy, the phenomenon of ventricular reverse remodeling is an important prognostic indicator in preventing future ventricular tachyarrhythmia episodes. In summation, we provide an overview of the possible selection criteria that can be used in identifying appropriate patients for ICD and/or CRT therapy, as supported by the data.

Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients with Mild Heart Failure: A MADIT-CRT Long-Term Follow-Up Sub-Study

Background —Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with LV dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase Systolic Blood Pressure (SBP). We therefore hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. Methods and Results —The independent contribution of SBP to outcome was analyzed in 1,267 patients with LBBB enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death, and CRT-D vs. ICD benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the ICD arm, each 10 mmHg decrement of SBP was independently associated with a significant 21% (p 2-fold risk-increase. CRT-D therapy provided the greatest HF or mortality risk reduction in patients with SBP SBP≥136 mmHg and HR=0.94, p=0.808 with SBP>136 mmHg (p for trend=0.001). Conclusions —In patients with mild HF, prolonged QRS, and LBBB, low SBP is related to higher risk of mortality or HF with ICD therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline systolic blood pressure values. Clinical Trial Registration —URL: http://www.clinicaltrials.gov. Unique identifier: [NCT00180271][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcirchf%2Fearly%2F2015%2F07%2F15%2FCIRCHEARTFAILURE.115.002208.atomBackground—Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. Methods and Results—The independent contribution of SBP to outcome was analyzed in 1267 patients with left bundle brunch block enrolled in Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death and CRT with defibrillator versus implantable cardioverter defibrillator benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the implantable cardioverter defibrillator arm, each 10-mm Hg decrement of SBP was independently associated with a significant 21% (P<0.001) increased risk for HF or death, and patients with lower quintile SBP (<110 mm Hg) experienced a corresponding >2-fold risk-increase. CRT with defibrillator provided the greatest HF or mortality risk reduction in patients with SBP<110 mm Hg hazard ratio of 0.34, P<0.001, when compared with hazard ratio of 0.52, P<0.001, in those with 110>SBP≥136 mm Hg and hazard ratio of 0.94, P=0.808, with SBP>136 mm Hg (P for trend=0.001). Conclusions—In patients with mild HF, prolonged QRS, and left bundle brunch block, low SBP is related to higher risk of mortality or HF with implantable cardioverter defibrillator therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline SBP values. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.