Saadia Sherazi

Left Ventricular Ejection Fraction Normalization in Cardiac Resynchronization Therapy and Risk of Ventricular Arrhythmias and Clinical Outcomes Results From the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT–CRT) Trial

Background— Appropriate guideline criteria for use of implantable cardioverter-defibrillators (ICDs) do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-defibrillator. Methods and Results— Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial who survived and had paired echocardiograms at enrollment and at 12 months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF ⩽35% [reference], 36%–50%, and >50%) on outcomes of ventricular tachyarrhythmias (VTAs), VTA ≥200 bpm, ICD shock, heart failure or death, and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization (>50%). The average follow-up was 2.2±0.8 years. The risk of VTA was reduced in patients with LVEF >50% (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.07–0.82; P=0.023) and LVEF of 36% to 50% (HR, 0.44; 95% CI, 0.28–0.68; P<0.001). Among patients with LVEF >50%, only 1 patient had VTA ≥200 bpm (HR, 0.16; 95% CI, 0.02–1.51), none were shocked by the ICD, and 2 died of nonarrhythmic causes. The risk of HF or death was reduced with improvements in LVEF (LVEF >50%: HR, 0.29; 95% CI, 0.09–0.97; P=0.045; and LVEF of 36%–50%: HR, 0.44; 95% CI, 0.28–0.69; P<0.001). For inappropriate ICD therapy, no additional risk reduction for LVEF>50% was seen compared with an LVEF of 36% to 50%. A total of 6 factors were associated with LVEF normalization, and patients with all factors present (n=42) did not experience VTAs (positive predictive value, 100%). Conclusions— Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present, and these patients could be considered for downgrade from CRT-defibrillator to CRT-pacemaker at the time of battery depletion if no VTAs have occurred. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.Background —Appropriate guideline criteria for use of ICDs do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-D. Methods and Results —Patients randomized to CRT-D from the MADIT-CRT trial, who survived and had paired echocardiograms at enrollment and at 12-months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF≤35% (reference), LVEF:36-50%, and LVEF>50%) on outcomes of ventricular tachyarrhythmias (VTA), VTA≥200 bpm, ICD-shock, heart failure or death and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization>50%. Average follow-up hereafter was 2.2±0.8 years. The risk of VTA was reduced in LVEF>50% (HR:0.24, CI:0.07-0.82, p=0.023) and LVEF:36-50% (HR:0.44, CI:0.28-0.68 p 50% only 1 had VTA≥200 bpm (HR:0.16, CI:0.02-1.51), none were shocked by the ICD and 2 died of non-arrhythmic causes. The risk of HF/death was reduced with improvements in LVEF (>50%: HR:0.29, CI:0.09-0.97 p=0.045 and LVEF:36-50%: HR:0.44, CI:0.28-0.69 p 50% was seen when compared to LVEF:36-50%. A total of 6 factors were associated with LVEF normalization and patients with all factors present (n=42) did not experience VTAs (PPV=100%). Conclusions —Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present and these patients could be considered for downgrade from CRT-D to CRT-P at time of battery-depletion if no VTAs have occurred. Clinical Trial Registration Information —www.clinicaltrials.org. Identifier: [NCT00180271][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcirculationaha%2Fearly%2F2014%2F10%2F09%2FCIRCULATIONAHA.114.011283.atom

Left Ventricular Ejection Fraction Normalization in Cardiac Resynchronization Therapy and Risk of Ventricular Arrhythmias and Clinical Outcomes: Results from the MADIT-CRT Trial

Background— Appropriate guideline criteria for use of implantable cardioverter-defibrillators (ICDs) do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-defibrillator. Methods and Results— Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) trial who survived and had paired echocardiograms at enrollment and at 12 months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF ⩽35% [reference], 36%–50%, and >50%) on outcomes of ventricular tachyarrhythmias (VTAs), VTA ≥200 bpm, ICD shock, heart failure or death, and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization (>50%). The average follow-up was 2.2±0.8 years. The risk of VTA was reduced in patients with LVEF >50% (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.07–0.82; P=0.023) and LVEF of 36% to 50% (HR, 0.44; 95% CI, 0.28–0.68; P<0.001). Among patients with LVEF >50%, only 1 patient had VTA ≥200 bpm (HR, 0.16; 95% CI, 0.02–1.51), none were shocked by the ICD, and 2 died of nonarrhythmic causes. The risk of HF or death was reduced with improvements in LVEF (LVEF >50%: HR, 0.29; 95% CI, 0.09–0.97; P=0.045; and LVEF of 36%–50%: HR, 0.44; 95% CI, 0.28–0.69; P<0.001). For inappropriate ICD therapy, no additional risk reduction for LVEF>50% was seen compared with an LVEF of 36% to 50%. A total of 6 factors were associated with LVEF normalization, and patients with all factors present (n=42) did not experience VTAs (positive predictive value, 100%). Conclusions— Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present, and these patients could be considered for downgrade from CRT-defibrillator to CRT-pacemaker at the time of battery depletion if no VTAs have occurred. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.Background —Appropriate guideline criteria for use of ICDs do not take into account potential recovery of left ventricular ejection fraction (LVEF) in patients treated with CRT-D. Methods and Results —Patients randomized to CRT-D from the MADIT-CRT trial, who survived and had paired echocardiograms at enrollment and at 12-months (n=752) were included. Patients were evaluated by LVEF recovery in 3 groups (LVEF≤35% (reference), LVEF:36-50%, and LVEF>50%) on outcomes of ventricular tachyarrhythmias (VTA), VTA≥200 bpm, ICD-shock, heart failure or death and inappropriate ICD therapy by multivariable Cox models. A total of 7.3% achieved LVEF normalization>50%. Average follow-up hereafter was 2.2±0.8 years. The risk of VTA was reduced in LVEF>50% (HR:0.24, CI:0.07-0.82, p=0.023) and LVEF:36-50% (HR:0.44, CI:0.28-0.68 p 50% only 1 had VTA≥200 bpm (HR:0.16, CI:0.02-1.51), none were shocked by the ICD and 2 died of non-arrhythmic causes. The risk of HF/death was reduced with improvements in LVEF (>50%: HR:0.29, CI:0.09-0.97 p=0.045 and LVEF:36-50%: HR:0.44, CI:0.28-0.69 p 50% was seen when compared to LVEF:36-50%. A total of 6 factors were associated with LVEF normalization and patients with all factors present (n=42) did not experience VTAs (PPV=100%). Conclusions —Patients who achieve LVEF normalization (>50%) have very low absolute and relative risk of VTAs and a favorable clinical course within 2.2 years of follow-up. Risk of inappropriate ICD therapy is still present and these patients could be considered for downgrade from CRT-D to CRT-P at time of battery-depletion if no VTAs have occurred. Clinical Trial Registration Information —www.clinicaltrials.org. Identifier: [NCT00180271][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00180271&atom=%2Fcirculationaha%2Fearly%2F2014%2F10%2F09%2FCIRCULATIONAHA.114.011283.atom

Physicians' Preferences and Attitudes About End-of-Life Care in Patients With an Implantable Cardioverter-Defibrillator

Clinical guidance is deficient regarding deactivation of implantable cardioverter-defibrillators (ICDs) in patients with terminal illnesses. We hypothesized that many physicians are apprehensive about discussing ICD deactivation with their dying patients. Thus, we conducted an anonymous survey of all the physicians in the Department of Medicine at Unity Health System in Rochester, NY. The survey collected information about the knowledge and preferences of these physicians regarding the medical, ethical, and legal issues involved in caring for patients with an ICD and terminal illness. Of the 204 surveys distributed, 87 (43%) were returned. Among the physicians who responded, 64 (74%) reported experience caring for a patient with an ICD and terminal illness. Forty physicians (46%) either thought it was illegal or were not sure if it was legal to deactivate an ICD in these circumstances. However, if reassured about the legality of discontinuing ICD therapy, 79 (91%) of these same respondents said that they would be willing to discuss voluntary ICD deactivation with their dying patients. With increased knowledge about managing the withdrawal of this potentially life-prolonging therapy, physicians are likely to become more skilled at caring for dying patients with an ICD.

End‐of‐Life Care in Patients with Implantable Cardioverter Defibrillators: A MADIT‐II Substudy

Implantable cardioverter defibrillator (ICD)‐delivered shocks can cause substantial distress, warranting consideration of ICD deactivation at end of life. This study was designed to describe the patterns of end‐of‐life management in patients with ICDs.

Effect of Biventricular Pacing During a Ventricular Sensed Event

Loss of biventricular (BiV) pacing occurs during ventricular sensed events such as frequent ventricular ectopy, nonsustained ventricular tachycardia, and intrinsic atrioventricular nodal conduction, such as in atrial fibrillation. Ventricular sense response (VSR) pacing, a novel cardiac resynchronization therapy pacing strategy, maintains BiV pacing during these sensed ventricular events. Patients who underwent echocardiographic optimization after BiV pacemaker implantation were enrolled, and aortic velocity-time integrals (VTIs) were recorded and compared during intrinsic conduction without pacing, optimized BiV pacing, and intrinsic conduction with VSR pacing alone. Thirty-two patients were enrolled (mean age 68 +/- 11 years, 78% men), with a mean baseline QRS duration of 164 +/- 24 ms and a mean left ventricular ejection fraction of 23 +/- 10%. The mean aortic VTI during intrinsic conduction with VSR pacing was 16.5 +/- 3.6 cm, compared with 15.3 +/- 3.4 cm during intrinsic conduction without pacing (p <0.001). The mean aortic VTI with optimized BiV pacing was 17.3 +/- 3.6 cm, significantly better (p <0.001) compared with intrinsic conduction without pacing. Improvements in aortic VTI were higher with optimized BiV pacing compared with VSR pacing alone (p = 0.02). In the subgroup of patients with left bundle branch block-type activation, the hemodynamic improvements realized with VSR pacing were similar to optimized BiV pacing. Mean aortic VTI improvements with VSR were similar in patients with ischemic and nonischemic cardiomyopathy. In conclusion, a cardiac resynchronization therapy algorithm that maintains BiV pacing during a ventricular sensed event appears to have an aortic VTI response that is significantly better compared with intrinsic conduction without pacing.

Predictors and clinical relevance of ventricular tachyarrhythmias in ambulatory patients with a continuous flow left ventricular assist device

BACKGROUND Patients with a left ventricular assist device (LVAD) are at high risk for ventricular tachyarrhythmias (VTAs). OBJECTIVE We aimed to identify clinical predictors of VTAs and subsequent outcomes after VTA in ambulatory LVAD patients. METHODS A retrospective study of 149 patients with a continuous flow HeartMate II LVAD who survived to discharge from index hospitalization after LVAD implantation was performed from January 10, 2005, to September 3, 2013. A multivariate Cox model was used to assess clinical predictors of VTAs. RESULTS During a mean follow-up period of 2.1 ± 1.2 years, 41 patients (28%) experienced VTAs; 30 of these patients (71%) had ventricular tachycardia, and 11 (29%) had ventricular fibrillation. History of VTAs before LVAD (hazard ratio [HR] 3.06; 95% confidence interval [CI] 1.57-5.96; P = .001) and history of atrial fibrillation (AF) (HR 3.13; 95% CI 1.60-6.11; P = .008) were the most powerful predictors of VTAs after LVAD implantation. There were 19 deaths (46%) among patients with VTAs and 15 deaths (14%) among patients without VTAs (P < .001). In multivariate analysis, time-dependent VTAs after LVAD implantation were associated with a significantly higher risk of all-cause mortality when compared with those without VTAs (HR 7.28; 95% CI 3.50-15.15; P < .001). CONCLUSION In ambulatory LVAD patients, history of VTAs before LVAD implantation and history of AF predict VTAs after LVAD implantation. VTAs are associated with an increased risk of mortality. In such patients, aggressive measures to control VTAs and AF should be considered.

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.

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.

Predictors of mortality in patients hospitalized for congestive heart failure with left ventricular ejection fraction ≥ 40%

BACKGROUND There are limited data regarding the predictors of mortality in patients with acute congestive heart failure (CHF) and left ventricular ejection fraction (LVEF) ≥ 40%. METHODS We evaluated clinical characteristics, mortality and prognostic factors in a sample of consecutive patients hospitalized for CHF with LVEF ≥ 40%. Multivariable Cox regression models were developed to predict mortality using baseline clinical characteristics and echocardiographic variables. RESULTS The study population consisted of 191 patients, mean age 70 ± 14.6 years (60% female) with average follow-up of 4.0 ± 2.8 years. Cumulative 5-year mortality was 58% in the entire population and it was 59% in men and 57% in women (p = 0.411). In multivariable analyses, predictors of mortality were the following: blood urea nitrogen (BUN) > 25 mg/dL (HR = 1.77; p = 0.002); absence of hypertension (HR = 1.58; p = 0.032), left ventricular end diastolic dimension (LVEDD) ≤ 4.1 cm (HR = 1.73; p = 0.011) and LVEF ≤ 45% (HR = 1.69; p = 0.027). CONCLUSIONS Patients hospitalized for heart failure with LVEF ≥ 40% have very high mortality. Absence of hypertension, elevated BUN and lower LVEF ≤ 45% indicate increased risk of short- and long-term mortality. Lower LVEDD is an independent predictor of mortality in heart failure patients with LVEF ≥ 40%.

Comparison of Low Versus High (>40 mm Hg) Pulse Pressure to Predict the Benefit of Cardiac Resynchronization Therapy for Heart Failure (from the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy Trial)

Low pulse pressure (PP) is associated with poor outcome in hospitalized patients with systolic heart failure (HF). However, the relation between PP and response to cardiac resynchronization therapy with defibrillator (CRT-D) is unknown. We aimed to evaluate the relation between preimplantation PP and echocardiographic response to CRT-D and subsequent clinical outcome after 1 year. The relation between preimplantation PP and echocardiographic response to CRT-D (defined as >15% reduction in left ventricular (LV) end-systolic volume at 1 year) was evaluated in 754 patients with CRT-D with left bundle branch block enrolled in Multicenter Automatic Defibrillator Cardioverter Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. The association between PP at 1 year and the risk for subsequent HF or death was evaluated using multivariate Cox model. Patients with high versus low PP (>40 vs ≤40 mm Hg [lower quartile]) had a significantly greater reduction in LV end-systolic volume, LV end-diastolic volume, and LV dyssynchrony (p<0.01 for all comparisons). In multivariate analysis, the presence of high PP was associated with a 3.5-fold (p<0.001) increase in the likelihood of a positive echocardiographic response to CRT-D. Patients with high PP (>40 mm Hg, >lower quartile) 1 year after CRT-D implantation experienced a 50% reduction in the risk of subsequent HF or death (p=0.001) and 63% reduction in death only (p=0.001), compared with patients with low PP. In conclusion, high baseline PP is an independent predictor of echocardiographic response to CRT-D, and high PP after device implantation is associated with improved subsequent clinical outcome.