Cardiac Resynchronization Therapy With Defibrillator Research Articles

Multiple Comorbidities and Response to Cardiac Resynchronization Therapy: MADIT-CRT Long-Term Follow-Up

BackgroundData regarding cardiac resynchronization therapy (CRT) in patients with multiple comorbidities are limited. ObjectivesThis study evaluated the association of multiple comorbidities with the benefits of CRT over implantable cardioverter-defibrillator (ICD) alone. MethodsWe examined 1,214 MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) study patients with left bundle branch block (LBBB) and 0, 1, 2, or ≥3 comorbidities, including renal dysfunction, hypertension (HTN), diabetes, coronary artery disease, history of atrial arrhythmias, history of ventricular arrhythmias, current smoking, and cerebrovascular accident. In an adjusted analysis, we analyzed risk of heart failure (HF) events or death by comorbidity group in all patients and in patients with CRT with defibrillator (CRT-D) versus ICD. Then we examined percent change in left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV ejection fraction, left atrial volume, and LV dyssynchrony at 1-year in CRT-D patients by comorbidity group. ResultsThere was an inverse relationship between comorbidity burden and improvements in LV end-systolic volume, LV end-diastolic volume, left ventricular ejection fraction, left atrial volume, and LV dyssynchrony. In an adjusted model, there was an increasing risk of death or nonfatal HF events with increasing comorbidity burden regardless of treatment group (p < 0.001). During a mean follow-up of 4.65 years, there was no interaction with respect to comorbidity burden and the benefit of CRT-D versus ICD only for death or nonfatal HF events (interaction p = 0.943). In the groups with greatest comorbidity burden (2 and ≥3), the absolute risk reduction associated with CRT-D over ICD alone appeared greater than that seen for groups with less comorbidity burden (0 and 1). ConclusionsDuring long-term follow-up of MADIT-CRT study patients with LBBB randomized to CRT-D, there were differences in HF or death risk and in the degree of reverse remodeling among comorbidity groups. However, the burden of comorbidity does not appear to compromise the clinical benefits of CRT-D compared with ICD alone.

Effect of Significant Weight Change on Inappropriate Implantable Cardioverter-Defibrillator Therapy.

Weight loss has been associated with adverse outcomes among heart failure (HF) patients, including those receiving cardiac resynchronization therapy with defibrillator (CRT-D). The effect of significant weight change on inappropriate implantable cardioverter-defibrillator (ICD) therapy among CRT-D patients is not well understood. We evaluated the impact of significant weight change at 1 year on subsequent inappropriate ICD therapy during follow-up among 993 CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. Patients were divided into three subgroups based on weight change at 1 year after enrollment: weight loss (weight loss ≥ 5%), weight gain (weight gain ≥ 5%), and stable weight (weight loss and weight gain < 5%). The primary end point was inappropriate ICD therapy. Secondary end point included inappropriate ICD therapy related to supraventricular arrhythmias (SVAs). There were 102 (10.3%) patients who experienced weight loss, 689 (69.4%) whose weight was stable, and 202 (20.3%) who gained weight at 1 year. Patients with weight loss had increased risk of subsequent inappropriate ICD therapy relative to patients with stable weight (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.39-3.98, P = 0.001) or weight gain (HR = 2.27, 95% CI: 1.18-4.38, P = 0.014). Furthermore, patients losing weight were at greater risk of subsequent inappropriate ICD therapy related to SVAs when compared to patients with stable weight (HR = 2.16, 95% CI: 1.18-3.95, P = 0.013) or weight gain (HR = 2.02, 95% CI: 0.95-4.29, P = 0.068). In mild HF patients receiving CRT-D, significant weight loss at 1 year is associated with increased risk of subsequent inappropriate ICD therapy, including risk related to SVAs.

Should physicians instead of industry representatives be the main actor of cardiac implantable electronic device follow-up? (Super Follow-up)

Objective:This retrospective study sought to research the adequacy of the follow-up and optimization of cardiac implantable electronic devices (CIEDs) performed by industry representatives.Methods:A total of 403 consecutive patients (35% females; median age, 67 years; age range 18–97 years) with either pacemakers (n=246), implantable cardioverter-defibrillators (ICDs), (n=117) or cardiac resynchronization therapy with defibrillator (CRT-D) (n=40) applied to our hospital’s outpatient pacemaker clinic for follow-up. These patients had been followed up by industry representatives alone until September 2013 and then by a cardiologist who is dealing with cardiac electrophysiology and has a knowledge of CIED follow-up.Results:It was ascertained that 117 (47.6%) of 246 patients with pacemakers had a programming error. Forty-three (36.8%) of 117 patients were symptomatic, and after reprogramming, all symptoms diminished partially or completely during the follow-up. Moreover, 30 (25.6%) of 117 patients with ICDs had a programming error. Furthermore, 6 (15%) of 40 patients with CRT-Ds had a programming error. To conclude, when all patients with CIEDs were assessed together, it was ascertained that 153 (38%) of 403 patients had programming errors.Conclusion:The prevalence of inappropriate programming of CIEDs by industry representatives was quite higher than expected. Therefore, our study strongly demonstrates that CIED follow-up should not be allowed to be performed entirely by manufacturers’ representatives alone.

The ethics of unilateral implantable cardioverter defibrillators and cardiac resynchronization therapy with defibrillator deactivation: patient perspectives.

Decisions about deactivation of implantable cardioverter defibrillators (ICDs) are complicated. Unilateral do-not-resuscitate (DNR) orders (against patient/family wishes) have been ethically justified in cases of medical futility. Unilateral deactivation of ICDs may be seen as a logical extension of a unilateral DNR order. However, the ethical implications of unilateral ICD deactivation have not been explored. Sixty patients who had an ICD or cardiac resynchronization therapy with defibrillator (CRT-D) were interviewed at a quaternary medical centre outpatient electrophysiology practice. Survey questions addressed whether deactivation of defibrillator function was included in advanced directives, whether deactivation constitutes physician-assisted suicide, and whether unilateral deactivation can be ethically justified. Responses were elicited to scenarios in which defibrillation function was deactivated in different contexts (including patient request to deactivate, existing DNR, and unilateral deactivation). Only 15% of respondents had thought about device deactivation if they were to develop a serious illness from which they were not expected to recover. A majority (53%) had advance directives, but only one mentioned what to do with the device. However, a majority (78%) did not consider deactivation of an ICD shocking function against patients' wishes to be ethical or moral. Management of ICDs and CRT-Ds as patients near the end of their lives creates ethical dilemmas. Few patients consider device deactivation at end-of-life, although a large majority believes that unilateral deactivation is not ethical/moral, even in the setting of medical futility. Advance care planning for these patients should address device deactivation.

Association Between a Prolonged PR Interval and Outcomes of Cardiac Resynchronization Therapy: A Report From the National Cardiovascular Data Registry.

A prolonged PR interval is common among cardiac resynchronization therapy (CRT) candidates; however, the association between PR interval and outcomes is unclear, and the data are conflicting. We conducted inverse probability weighted analyses of 26 451 CRT-eligible (ejection fraction ≤35, QRS ≥120 ms) patients from the National Cardiovascular Data Registry ICD Registry to assess the association between a prolonged PR interval (≥230 ms), receipt of CRT with defibrillator (CRT-D) versus implantable cardioverter defibrillator (ICD), and outcomes. We first tested the association between a prolonged PR interval and outcomes among patients stratified by device type. Next, we performed a comparative effectiveness analysis of CRT-D versus ICD among patients when stratified by PR interval. Using Medicare claims data, we followed up with patients up to 5 years for incident heart failure hospitalization or death. Patients with a PR≥230 ms (15%; n=4035) were older and had more comorbidities, including coronary artery disease, atrial arrhythmias, diabetes mellitus, and chronic kidney disease. After risk adjustment, a PR≥230 ms (versus PR<230 ms) was associated with increased risk of heart failure hospitalization or death among CRT-D (hazard ratio, 1.23; 95% confidence interval, 1.14-1.31; P<0.001) but not ICD recipients (hazard ratio, 1.08; 95% confidence interval, 0.97-1.20; P=0.17) (Pinteraction=0.043). CRT-D (versus ICD) was associated with lower rates of heart failure hospitalization or death among patients with PR<230 ms (hazard ratio, 0.79; 95% confidence interval, 0.73-0.85; P<0.001) but not PR≥230 ms (hazard ratio, 1.01; 95% confidence interval, 0.87-1.17; P=0.90) (Pinteraction=0.0025). A PR≥230 ms is associated with increased rates of heart failure hospitalization or death among CRT-D patients. The real-world comparative effectiveness of CRT-D (versus ICD) is significantly less among patients with a PR≥230 ms in comparison with patients with a PR<230 ms.

Late Gadolinium Enhancement Amount As an Independent Risk Factor for the Incidence of Adverse Cardiovascular Events in Patients with Stage C or D Heart Failure.

Background: Myocardial fibrosis (MF) is a risk factor for poor prognosis in dilated cardiomyopathy (DCM). Late gadolinium enhancement (LGE) of the myocardium on cardiac magnetic resonance (CMR) represents MF. We examined whether the LGE amount increases the incidence of adverse cardiovascular events in patients with stage C or D heart failure (HF).Methods: Eighty-four consecutive patients with stage C or D HF, either ischemic or non-ischemic, were enrolled. Comprehensive clinical and CMR evaluations were performed. All patients were followed up for a composite endpoint of cardiovascular death, heart transplantation, and cardiac resynchronization therapy with defibrillator (CRT-D).Results: LGE was present in 79.7% of the end-stage HF patients. LGE distribution patterns were mid-wall, epi-myocardial, endo-myocardial, and the morphological patterns were patchy, transmural, and diffuse. During the average follow-up of 544 days, 13 (15.5%) patients had endpoint events: 7 patients cardiac death, 2 patients heart transplantation, and 4 patients underwent CRT-D implantation. On univariate analysis, LGE quantification on cardiac magnetic resonance, blood urine nitrogen, QRS duration on electrocardiogram, left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV) on CMR had the strongest associations with the composite endpoint events. However, on multivariate analysis for both Model I (after adjusting for age, sex, and body mass index) and Model II (after adjusting for age, sex, BMI, renal function, QRS duration, and atrial fibrillation on electrocardiogram, the etiology of HF, LVEF, CMR-LVEDD, and CMR-LVEDV), LGE amount was a significant risk factor for composite endpoint events (Model I 6SD HR 1.037, 95%CI 1.005–1.071, p = 0.022; Model II 6SD HR 1.045, 95%CI 1.001–1.084, p = 0.022).Conclusion: LGE amount from high-scale threshold on CMR increased the incidence of adverse cardiovascular events for patients in either stage C or D HF.

A qualitative study of decision-making about the implantation of cardioverter defibrillators and deactivation during end-of-life care

BackgroundImplantable cardioverter defibrillators (ICDs) are recommended for patients at high risk of sudden cardiac death or for survivors of cardiac arrest. All ICDs combine a shock function with a pacing function to treat fast and slow heart rhythms, respectively. The pacing function may be very sophisticated and can provide so-called cardiac resynchronisation therapy for the treatment of heart failure using a pacemaker (cardiac resynchronisation therapy with pacemaker) or combined with an ICD [cardiac resynchronisation therapy with defibrillator (CRT-D)]. Decision-making about these devices involves considering the benefit (averting sudden cardiac death), possible risks (inappropriate shocks and psychological problems) and the potential need for deactivation towards the end of life.ObjectivesTo explore patients’/relatives’ and clinicians’ views/experiences of decision-making about ICD and CRT-D implantation and deactivation, to establish how and when ICD risks, benefits and consequences are communicated to patients, to identify individual and organisational facilitators and barriers to discussions about implantation and deactivation and to determine information and decision-support needs for shared decision-making (SDM).Data sourcesObservations of clinical encounters, in-depth interviews and interactive group workshops with clinicians, patients and their relatives.MethodsObservations of consultations with patients being considered for ICD or CRT-D implantation were undertaken to become familiar with the clinical environment and to optimise the sampling strategy. In-depth interviews were conducted with patients, relatives and clinicians to gain detailed insights into their views and experiences. Data collection and analysis occurred concurrently. Interactive workshops with clinicians and patients/relatives were used to validate our findings and to explore how these could be used to support better SDM.ResultsWe conducted 38 observations of clinical encounters, 80 interviews (44 patients/relatives, seven bereaved relatives and 29 clinicians) and two workshops with 11 clinicians and 11 patients/relatives. Patients had variable knowledge about their conditions, the risk of sudden cardiac death and the clinical rationale for ICDs, which sometimes resulted in confusion about the potential benefits. Clinicians used various metaphors, verbal descriptors and numerical risk methods, including variable disclosure of the potential negative impact of ICDs on body image and the risk of psychological problems, to convey information to patients/relatives. Patients/relatives wanted more information about, and more involvement in, deactivation decisions, and expressed a preference that these decisions be addressed at the time of implantation. There was no consensus among clinicians about the initiation or timing of such discussions, or who should take responsibility for them. Introducing deactivation discussions prior to implantation was thus contentious; however, trigger points for deactivation discussions embedded within the pathway were suggested to ensure timely discussions.LimitationsOnly two patients who were prospectively considering deactivation and seven bereaved relatives were recruited. The study also lacks the perspectives of primary care clinicians.ConclusionsThere is discordance between patients and clinicians on information requirements, in particular the potential consequences of implantation on psychological well-being and quality of life in the short and long term (deactivation). There were no agreed points across the care pathway at which to discuss deactivation. Codesigned information tools that present balanced information on the benefits, risks and consequences, and SDM skills training for patients/relative and clinicians, would support better SDM about ICDs.Future workMultifaceted SDM interventions that focus on skills development for SDM combined with decision-support tools are warranted, and there is a potential central role for heart failure nurses and physiologists in supporting and preparing patients/relatives for such discussions.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

Effect of cardiac resynchronization therapy on the risk of ventricular tachyarrhythmias in patients with chronic kidney disease.

The effect of chronic kidney disease (CKD) on benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in reducing ventricular tachyarrhythmia (VTA) risk among mild heart failure (HF) patients is not well understood. We evaluated the impact of baseline renal function on VTAs in 1274 left bundle branch block (LBBB) patients enrolled in MADIT-CRT. Two prespecified subgroups were created based on estimated glomerular filtration rate (GFR): GFR <60 (n=413) and GFR ≥60ml/min/1.73m2 (n=861). Primary end point was ventricular tachycardia/ventricular fibrillation/death (VT/VF/death). Secondary end points were any VT/VF and ventricular tachycardia ≥ 200bpm or VF (fast VT/VF). There were 413 (32%) LBBB patients presenting with CKD, primarily of moderate severity (GFR mean 48.1±8.3). For patients with and without CKD, CRT-D was associated with lower risk of the primary end point (GFR<60: HR=0.61, 95% CI: 0.41-0.89, p=.010; GFR≥60: HR=0.58, 95% CI: 0.52-0.89, p=.005), relative to ICD-only treatment. For patients in both renal function categories, CRT-D in comparison to ICD alone was associated with lower risk of VT/VF (GFR<60: HR=0.68, 95% CI: 0.42-1.10, p=.113; GFR≥60: HR=0.65, 95% CI: 0.48-0.88, p=.005) and fast VT/VF (GFR<60: HR=0.49, 95% CI: 0.25-0.96, p=.038; GFR≥60: HR=0.55, 95% CI: 0.39-0.80, p=.001), when accounting for competing mortality risk. This effect was independent of CRT-induced reverse remodeling. Among mild HF patients with LBBB, those with and without CKD both derived benefit from CRT-D in risk reduction in VTAs, independent of cardiac reverse remodeling.

Does defibrillation testing influence outcomes after CRT-D implantation? A cause-of-death analysis from the DAI-PP study

BackgroundLittle data address the usefulness of defibrillation testing in patients with prolonged QRS duration, known for more advanced myocardial disease. We aimed to compare baseline characteristics and outcomes between patients who underwent defibrillation testing (DT+) and those who did not (DT−), immediately after the implantation of a cardiac resynchronization therapy with defibrillator (CRT-D). MethodsData from all patients with ischemic or non-ischemic cardiomyopathy implanted in primary prevention with a CRT-D in 12 French centers were considered for analysis (2002–2012). ResultsOut of the 1516 patients with DT information available, DT was performed in 958(63%) patients. Compared to DT− patients, DT+ patients presented no significant differences in terms of age (65.1±10.8 vs 64.7±10.3years, p=0.45), LVEF (25%[20.0–30.0] vs 25%[20.5–30.0], p=0.30), or etiologies of heart failure (ischemic: 49.6% vs 46.9%, p=0.32). By contrast, DT+ patients were less likely to present atrial fibrillation (25.3% vs 33.4%, p=0.001), renal insufficiency (eGFR<60ml/min in 45.3% vs 51.7%, p=0.04) and NYHA functional class≥III (68.9% vs 77.4%, p=0.0006). All of the three perioperative deaths occurred in the DT+ group and were related to DT itself. After a mean follow-up of 3.1±2.1years, the adjusted incidence of overall mortality was lower among DT+ patients (adjusted HR 0.6, 95%CI 0.4–0.7, p<0.0001). However, ICD-unresponsive sudden deaths remained very rare and no more frequently observed among DT− patients (p=0.41). ConclusionsIn our cohort, the higher (up to 40%) mortality at midterm among DT− patients is mainly reflecting their more severe cardiac disease, rather than a higher rate of ICD-unresponsive sudden death.

Telemonitoring in heart failure patients treated by cardiac resynchronisation therapy with defibrillator (CRT-D): the TELECART Study.

Telemonitoring (TM) is a safe and efficient monitoring system for internal cardioverter defibrillator device (ICD) recipients. TM has been used to track info on the clinical status of heart failure patients treated by ICD and/or cardiac resynchronisation therapy defibrillator (CRT-D). The aim of this study was to investigate the impact of TM on clinical outcomes in a population of CRT-D patients with heart failure. In a multicentre, randomised study, patients with chronic heart failure, New York Heart Association (NYHA) functional class II or III, left bundle branch block, severe left ventricle ejection fraction reduction (LVEF < 35%) have been identified and screened. One hundred and ninety-one patients have been randomised to receive either a CRT-D with TM or a CRT-D with traditional ambulatory monitoring (control group) and completed the 12-month study follow-up. Primary endpoints were all cause death, cardiac death and hospital admission for heart failure. Secondary endpoints were atrial fibrillation, sustained episodes, non-sustained and self terminated ventricular tachyarrhythmia, sustained ventricular tachycardia, and ventricular fibrillation, ICD shocks and percentage of CRT-D responder patients. Univariate analysis identified the following factors predicting hospitalisation: TM, age, chronic kidney disease, hypercholesterolaemia, LVEF and NYHA class. At multivariate analysis, TM was the only factor predicting heart failure hospitalisation (hazard ratio 0.6, 0.42-0.79, 95% CI, p = 0.002), without affecting overall mortality and cardiac deaths events. Taken together, our data indicate the importance of TM in predicting heart failure hospitalisation in patients treated with CRT-D.

Reduced Mortality Associated WithQuadripolar Compared to BipolarLeftVentricular Leads in CardiacResynchronization Therapy.

The study sought to compare survival, lead deactivation, and lead replacement with quadripolar versusbipolar leads using a retrospective cohort of patients with newly implanted cardiac resynchronization therapy (CRT) systems. In CRT, quadripolar left ventricular (LV) leads offer alternative pacing sites and vectors not available with bipolar LV leads, which may improve the effectiveness of the therapy. Using nationwide data from device implant registration records of a single manufacturer, we identified patients with a de novo cardiac resynchronization therapy with defibrillation (CRT-D) implanted between November 30, 2011, and May 31, 2013. Patients were followed for up to 24 months. The primary predictor was LV lead type (quadripolar Quartet [St. Jude Medical, St. Paul, Minnesota] LV lead or bipolar LV lead). The primary outcome was death and the secondary outcomes were LV lead replacement and deactivation. Among 23,570 patients (69.5 ± 11.1 years of age; 28% female; median follow-up time 1.14 years), 18,406 had quadripolar and 5,164 had bipolar LV leads. The quadripolar and bipolar groups had 5.04 and 6.45 deaths per 100 patient-years, respectively (p< 0.001). After multivariate adjustment, the quadripolar lead was associated with a lower risk of deactivation (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.46 to 0.84; p= 0.002), replacement (HR:0.67; 95% CI: 0.55 to 0.83; p< 0.001), and death (HR: 0.77; 95% CI: 0.69 to 0.86; p< 0.001). In this observational study of CRT-D devices, use of a quadripolar, compared to a bipolar LV lead, was associated with a reduction in LV lead deactivation, replacement, and mortality.

Veno-venous loop through coronary sinus for LV lead placement during cardiac resynchronization therapy

Left ventricular lead placement in the appropriate branch of coronary sinus is the key to successful cardiac resynchronization therapy (CRT) and this step is technically challenging. We describe a case of non-ischemic cardiomyopathy with heart failure, taken up for cardiac resynchronization therapy with defibrillator (CRT-D) implantation. The quadripolar left ventricular lead was impossible to advance into the target lateral branch of the coronary sinus. We made a veno-venous loop, advancing the coronary guidewire through the middle cardiac vein to coronary sinus and then to superior vena cava. The guidewire then snared through the same left subclavian vein and exteriorized. Over this loop, the left ventricular lead of the CRT-D device was implanted successfully. This novel approach can be used to successfully implant the LV lead in difficult to implant situations, obviating the need for thoracotomy or other methods of LV lead implantation.

Comparative Effectiveness of CRT-D Versus Defibrillator Alone in HF Patients With Moderate-to-Severe Chronic Kidney Disease

BackgroundPatients with moderate-to-severe chronic kidney disease (CKD) are poorly represented in clinical trials of cardiac resynchronization therapy (CRT). ObjectivesThis study sought to assess the real-world comparative effectiveness of CRT with defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) alone in CRT-eligible patients with moderate-to-severe CKD. MethodsWe conducted an inverse probability-weighted analysis of 10,946 CRT-eligible patients (ejection fraction <35%, QRS >120 ms, New York Heart Association functional class III/IV) with stage 3 to 5 CKD in the National Cardiovascular Data Registry (NCDR) ICD Registry, comparing outcomes between patients who received CRT-D (n = 9,525) versus ICD only (n = 1,421). Outcomes were obtained via Medicare claims and censored at 3 years. The primary endpoint of heart failure (HF) hospitalization or death and the secondary endpoint of death were assessed with Cox proportional hazards models. HF hospitalization, device explant, and progression to end-stage renal disease were assessed using Fine-Gray models. ResultsAfter risk adjustment, CRT-D use was associated with a reduction in HF hospitalization or death (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.78 to 0.91; p < 0.0001), death (HR: 0.85; 95% CI: 0.77 to 0.93; p < 0.0004), and HF hospitalization alone (subdistribution HR: 0.84; 95% CI: 0.76 to 0.93; p < 0.009). Subgroup analyses suggested that CRT was associated with a reduced risk of HF hospitalization and death across CKD classes. The incidence of in-hospital, short-term, and mid-term device-related complications did not vary across CKD stages. ConclusionsIn a nationally representative population of HF and CRT-eligible patients, use of CRT-D was associated with a significantly lower risk of the composite endpoint of HF hospitalization or death among patients with moderate-to-severe CKD in the setting of acceptable complication rates.

Abstract 14660: Effect of PR Interval on Mortality Reduction With Cardiac Resynchronization Therapy - A Secondary Analysis of the COMPANION Trial

Introduction: Prolonged PR intervals may impair atrioventricular mechanical coupling and adversely affect cardiac performance. We hypothesize that patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals will have improved survival from cardiac resynchronization therapy with defibrillator (CRT-D) regardless of whether left bundle branch block (LBBB) or non-LBBB is present. Methods: Patients enrolled in the optimal pharmacologic therapy (OPT) and CRT-D arms of the COMPANION trial were included in a multivariable Cox model of all-cause mortality as a function of presence of LBBB and value of PR interval at baseline. Hazard ratios representing the mortality reduction for CRT-D versus OPT were estimated together with pointwise 95% confidence intervals (CIs). Results: A total of 308 OPT and 595 CRT-D patients were included in the analysis. In both the LBBB (n=648) and non-LBBB (n=255) subgroups, the mortality reduction associated with CRT-D compared to OPT was greater with increasingly prolonged baseline PR interval (Figure 1, p=0.02 for each subgroup). Hazard ratios for CRT-D versus OPT (with 95% CIs) for PR intervals of 200ms and 250ms were 0.51 [0.35,0.74] and 0.30 [0.18,0.50] respectively for the LBBB subgroup, and 0.86 [0.50,1.5] and 0.39 [0.18,0.86] respectively for the non-LBBB subgroup. For non-LBBB patients with PR interval ≤200ms, there was no evidence of mortality benefit with CRT-D (p=0.60). Conclusions: In patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals, restoration of atrioventricular mechanical coupling with CRT-D may improve survival in both LBBB and non-LBBB recipients. In patients with non-LBBB, a benefit from CRT-D may occur in patients with prolonged PR intervals. Figure 1: Risk for all-cause mortality by hazard ratios stratified according to PR interval quartiles.

Abstract 18480: Mortality Risk in Married and Unmarried ICD and CRT-D Patients With Mild Heart Failure: A MADIT-CRT Sub-study

Background: Married patients have been shown to have a lower risk for adverse cardiovascular outcomes. However, the risk of heart failure or death, and death alone in married versus unmarried patients with left ventricular (LV) dysfunction and an implantable cardioverter defibrillator (ICD), and the effect of cardiac resynchronization therapy with defibrillator (CRT-D) are unknown. Methods: In MADIT-CRT, we evaluated the long-term clinical outcomes of all-cause mortality, and heart failure (HF) or death in married and common law patients compared to the unmarried (single/divorced/widowed) with left bundle branch block (LBBB) and CRT-D vs. an ICD-only. Results: There were 937 married patients and 344 unmarried patients with LBBB. Married patients were more likely to be men, white, smokers, and heavier. During a median follow-up of 5.6 years, married/common law ICD patients had a significantly lower incidence of death compared to unmarried patients (p=0.004) (Figure). In multivariate analysis in the ICD-only sub-group, married or common-law patients had a 39% lower risk of all-cause mortality (HR 0.46, 95% CI 0.30 - 0.71, p&lt;0.001) when compared to the unmarried. However, in the CRT-D group, the survival benefit was attenuated in married/common-law patients (HR 0.74, 95% CI 0.51 - 1.06, p=0.10) compared to the unmarried (HR 0.40, 95% CI 0.23 - 0.69, p&lt;0.001, interaction p=0.07). There were no differences in clinical outcomes of HF or death in married and unmarried patients with an implanted CRT-D vs. ICD-only, or in patients with non-LBBB ECG pattern. Conclusions: During long-term follow-up of mild HF patients with LV dysfunction, married/common-law patients were at a significantly lower risk for death compared to those not married. In married patients, CRT-D was associated with an attenuated survival benefit when compared to their unmarried counterparts.

Abstract 14303: Low Global Longitudinal Strain in Ischemic Cardiomyopathy Patients at Baseline is Associated With Ventricular Arrhythmias After Cardiac Resynchronization Therapy

Introduction: Heart failure (HF) patients have an increased risk for ventricular arrhythmias (VA) and in particular patients with ischemic cardiomyopathy (ICM) have a worse prognosis after cardiac resynchronization therapy with defibrillator (CRT-D) compared with non-ischemic patients. Hypothesis: We hypothesize that global longitudinal strain (GLS) at baseline has the ability to identify ICM patients at higher risk for VA after CRT-D. Methods: We prospectively studied 175 consecutive HF patients implanted with CRT-D from a single center. All of them had class II-IV HF symptoms, LV ejection fraction (≤35%), QRS≥120 ms. GLS was measured from the three standard apical views and presented as absolute values. Outcome event was defined as VA (anti-tachycardia pacing or appropriate shock) after CRT in the first 2 years of follow-up. Results: Of 175 patients aged 65±11 years, 135 (77%) were male and 115 (66%) had ICM. They suffered 34 (19%) VA events over 2 years. Mean GLS of the population was 8.1±3.0. GLS (&lt; 6.5%) was associated with VA events after CRT-D with a sensitivity of 70% and specificity of 56%. A cutoff of GLS&lt;6.5% was associated with greater VA events in the ICM patients with HR 2.92 (95% confidence interval 1.48 to 5.77, p=0.002). A similar significant association of GLS was not seen in the non ICM patients (p=0.12). Conclusions: Low GLS (&lt;6.5% in absolute values) in ICM patients is associated with increased risk for VA after CRT-D and might represent more extensive myocardial scarring and has prognostic implications.

Abstract 17167: Risk Stratification for Long-term Survival Benefit With Cardiac Resynchronization Therapy in Mild Heart Failure Patients

Background: Cardiac resynchronization therapy (CRT) has been shown to reduce heart failure (HF) events or death in mild HF patients with left bundle branch block (LBBB) ECG pattern. However, risk stratification for long-term mortality benefit with CRT in this cohort is currently lacking. Methods: The study population comprised 1266 patients with LBBB enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). A clinical risk score was developed using best-subset proportional hazards regression analysis in patients randomized to CRT with defibrillator (CRT-D) to predict survival benefit. Cox proportional hazards regression analysis was used to evaluate risk reduction of death by CRT-D versus an implantable cardioverter defibrillator (ICD)-only among the risk score groups. Results: We identified four clinical variables predicting outcome in CRT-D patients: age≥65, creatinine≥1.4 mg/dl, coronary artery bypass graft [CABG] in the patient history, and left ventricular ejection fraction [LVEF] &lt; 26%. Five-year risk of mortality was 4% with no risk factor (low risk, n=357), 6% with 1 risk factor (n=500), 12% with 2 risk factors, and 27% with 3 risk factors (n=123); there were no patients with 4 risk factors. The mortality benefit from CRT-D vs. an ICD-only showed a U-shaped pattern with no significant benefit in patients with no risk factor (HR=0.77, CI 0.32-1.85, p=0.553), 46% reduction with 1 risk factor (HR=0.54, CI 0.32-0.89, p=0.017), 45% reduction with 2 risk factors (HR=0.55, CI 0.34-0.90, p=0.018), and no benefit with 3 risk factors (HR=0.77, CI 0.32-1.85, p=0.553). Conclusions: In MADIT-CRT, mild HF patients with LBBB with an intermediate mortality risk derived long-term survival benefit from CRT-D vs. an ICD-only. However, no survival benefit was observed in patients with low risk or a very-high risk.

Long-term outcome with cardiac resynchronization therapy in mild heart failure patients with left bundle branch block from US and Europe MADIT-CRT.

Early intervention with cardiac resynchronization therapy with defibrillator (CRT-D) in mild heart failure (HF) patients with a left bundle branch block (LBBB) ECG pattern was associated with a significant reduction in mortality in the long-term MADIT-CRT trial. Whether patients in MADIT-CRT enrolled from centers in the USA and in Europe have different long-term clinical response to CRT-D remains unknown. We compared the baseline clinical characteristics and clinical and echocardiographic long-term clinical response to CRT-D between MADIT-CRT patients with LBBB who were enrolled in USA (n=871) and European centers (n=392). Although European patients had more advanced heart disease than US patients, CRT-D was associated with similar 60% (p<0.001) reductions in the risk of HF in US and European patients when compared to ICD-only therapy after adjustment for relevant baseline clinical covariates. US patients had significant long-term mortality reduction (38%, p=0.02) while among European patients the survival benefit associated with CRT-D was not statistically significant (HR 0.73, p=0.18); subgroup analyses revealed a significantly greater CRT-D benefit among women who were enrolled in the USA, whereas no significant gender difference in the clinical benefit of CRT-D was observed in the European cohort. Reverse remodeling at 1year was associated with significantly better clinical outcomes in both groups. Despite differences in baseline disease severity, European and US patients with LBBB experienced a similar clinical and echocardiographic response to cardiac resynchronization therapy during long-term follow-up. http://clinicaltrials.gov/ct2/show/NCT00180271 .

Digoxin therapy and associated clinical outcomes in the MADIT-CRT trial.

Digoxin's pharmacological, hemodynamic, and electrophysiological properties are well understood. However, in modern heart failure (HF) treatment, its effect has yet to be fully investigated. The aim of the present study was to determine the effects of digoxin on outcomes in patients with mild HF implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D) device. We investigated the effect of digoxin treatment on the end points of HF/death, HF alone, death alone, and ventricular tachycardia or ventricular fibrillation (VT/VF) in 1820 patients with mild HF (New York Heart Association class I and II), prolonged QRS duration (≥130 ms), and reduced left ventricular ejection fraction (≤30%) enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy trial. Multivariate Cox proportional hazards regression models were used to determine the effect of time-dependent digoxin usage on the end points. Digoxin therapy was not associated with an increased or decreased risk of HF/death (hazard ratio [HR] 1.07; 95% confidence interval [CI] 0.86-1.33; P = .0.56), HF alone (HR 1.1.04; 95% CI 0.82-1.32; P = .76), or death alone (HR 0.93; 95% CI 0.67-1.32; P = .71). However, digoxin was associated with a significant 41% increased risk of VT/VF (HR 1.41; 95% CI 1.14-1.75; P = .002), which was driven by a significantly increased risk of VT/VF with heart rate ≥200 beats/min (HR 1.65; 95% CI 1.27-2.15; P ≤ .001), whereas no increased risk of VT/VF with heart rate <200 beats/min was evident (HR 1.20; 95% CI 0.92-1.57; P = .19). No significant differences in digoxin's effect on any of the end points were found between patients with ICD and patients with CRT-D (interaction P > .5). The use of digoxin in patients with mild HF implanted with an ICD or CRT-D device was not associated with reductions in HF/death events. However, digoxin therapy was associated with an increased risk of high-rate VT/VF (≥200 beats/min).

Does Age Influence Cardiac Resynchronization Therapy Use and Outcome?

ObjectivesThis study sought to describe the use of CRT-D and its association with survival for older patients. BackgroundMany patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) in practice are older than those included in clinical trials. MethodsWe identified patients undergoing ICD implantation in the National Cardiovascular Disease Registry (NCDR) ICD registry from 2006 to 2009, who also met clinical trial criteria for CRT, including left ventricular ejection fraction (LVEF) ≤35%, QRS ≥120 ms, and New York Heart Association (NYHA) functional class III or IV. NCDR registry data were linked to the social security death index to determine the primary outcome of time to death from any cause. We identified 70,854 patients from 1,187 facilities who met prior trial criteria for CRT-D. The mean age of the 58,147 patients receiving CRT-D was 69.4 years with 6.4% of patients age 85 or older. CRT use was 80% or higher among candidates in all age groups. Follow-up was available for 42,285 patients age ≥65 years at 12 months. ResultsReceipt of CRT-D was associated with better survival at 1 year (82.1% vs. 77.1%, respectively) and 4 years (54.0% vs. 46.2% , respectively) than in those receiving only an ICD (p < 0.001). The CRT association with improved survival was not different for different age groups (p = 0.86 for interaction). ConclusionsMore than 80% of older patients undergoing ICD implantation who were candidates for a CRT-D received the combined device. Mortality in older patients undergoing ICD implantation was high but was lower for those receiving CRT-D.