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      Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study

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      European Heart Journal
      Oxford University Press
      Heart failure, Sudden death, Cardioverter defibrillator, Competing risk, Cardiac resynchronization

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          Abstract

          Aims

          The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice.

          Methods and results

          A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older ( P < 0.0001), less often male ( P < 0.0001), more symptomatic ( P = 0.0005), with less coronary artery disease ( P = 0.003), wider QRS ( P = 0.002), more atrial fibrillation ( P < 0.0001), and more co-morbidities ( P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41–94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56–2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07–2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death.

          Conclusion

          When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

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          Most cited references28

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          Cardiac-resynchronization therapy for the prevention of heart-failure events.

          This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter-defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heart-failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P=0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT00180271.) 2009 Massachusetts Medical Society
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            Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial.

            An important determinant of successful cardiac resynchronization therapy for heart failure is the position of the left ventricular (LV) pacing lead. The aim of this study was to analyze the impact of the LV lead position on outcome in patients randomized to cardiac resynchronization-defibrillation in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) study. The location of the LV lead was assessed by means of coronary venograms and chest x-rays recorded at the time of device implantation. The LV lead location was classified along the short axis into an anterior, lateral, or posterior position and along the long axis into a basal, midventricular, or apical region. The primary end point of MADIT-CRT was heart failure (HF) hospitalization or death, whichever came first. The LV lead position was assessed in 799 patients, (55% patients ≥65 years of age, 26% female, 10% LV ejection fraction ≤25%, 55% ischemic cardiomyopathy, and 71% left bundle-branch block) with a follow-up of 29±11 months. The extent of cardiac resynchronization therapy benefit was similar for leads in the anterior, lateral, or posterior position (P=0.652). The apical lead location compared with leads located in the nonapical position (basal or midventricular region) was associated with a significantly increased risk for heart failure/death (hazard ratio=1.72; 95% confidence interval, 1.09 to 2.71; P=0.019) after adjustment for the clinical covariates. The apical lead position was also associated with an increased risk for death (hazard ratio=2.91; 95% confidence interval, 1.42 to 5.97; P=0.004). LV leads positioned in the apical region were associated with an unfavorable outcome, suggesting that this lead location should be avoided in cardiac resynchronization therapy. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00180271.
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              Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase].

              The CArdiac REsynchronization-Heart Failure study randomized patients with left ventricular ejection fraction < or =35%, markers of cardiac dyssynchrony, and persistent moderate or severe symptoms of heart failure despite pharmacological therapy, to implantation of a cardiac resynchronization therapy (CRT) device or not. The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [median 29.6, interquartile range (IQR) 23.6-34.6]. Prior to study closure, an extension phase lasting a further 8 months (allowing time for data analysis and presentation) was declared during which cross-over was discouraged. This was an extension of the already reported open-label randomized trial described above. The primary outcome of the extension phase was all-cause mortality from the time of randomization to completion of the extension phase. The secondary outcome was mode of death. The mean follow-up was 37.4 months (median 37.6, IQR 31.5-42.5, range 26.1-52.6 months). There were 154 deaths (38.1%) in 404 patients assigned to medical therapy and 101 deaths (24.7%) in 409 patients assigned to CRT (hazard ratio 0.60, 95% CI 0.47-0.77, P<0.0001) without evidence of heterogeneity in pre-specified subgroups. A reduction in the risk of death due to heart failure (64 vs. 38 deaths; hazard ratio 0.55, 95% CI 0.37-0.82, P=0.003) and sudden death was observed (55 vs. 32; hazard ratio 0.54, 95% CI 0.35-0.84, P=0.005). The benefits of CRT observed in the main trial persist or increase with longer follow-up. Reduction in mortality was due to fewer deaths both from worsening heart failure and from sudden death.
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                Author and article information

                Journal
                Eur Heart J
                Eur. Heart J
                eurheartj
                ehj
                European Heart Journal
                Oxford University Press
                0195-668X
                1522-9645
                01 November 2015
                01 September 2015
                01 September 2015
                : 36
                : 41 , Special Issue on the 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death
                : 2767-2776
                Affiliations
                [1 ]Cardiology Department, European Georges Pompidou Hospital , Paris, France
                [2 ]Paris Descartes University , Paris, France
                [3 ]Paris Cardiovascular Research Centre, Paris , France
                [4 ]Pontchaillou University Hospital and INSERM 1099 , CIC-IT 804 Rennes, France
                [5 ]Clinique Pasteur , Toulouse, France
                [6 ]Lille University Hospital and University of Lille , Lille, France
                [7 ]Arrhythmia Department, University Hospital , Grenoble, France
                [8 ]Epidemiology Unit, IRSN , Paris, France
                [9 ]Centre Cardiologique du Nord , Saint Denis, France
                [10 ]Cardiology Division, Hôpital La Timone , Marseille, France
                [11 ]French Society of Cardiology, Paris, France
                [12 ]Amiens University Hospital , Amiens, France
                [13 ]Caen University Hospital , Caen, France
                [14 ]Nouvelles Cliniques Nantaises , Nantes, France
                [15 ]Clinique Saint Gatien , Tours, France
                [16 ]Cardiology Department, La Pitié-Salpêtrière Hospital, AP-HP , Paris, France
                [17 ]Cardiology Division, Rouen University Hospital , Rouen, France
                [18 ]East Lyon School of Medicine, Louis Pradel Hospital , Bron, France
                [19 ]Cardiology Division, Rangueil University Hospital , Toulouse, France
                [20 ]Cardiology Division, Nancy University Hospital , Nancy, France
                [21 ]Haut-Lévêque Hospital , Bordeaux, France
                [22 ]Saint Joseph Hospital , Paris, France
                [23 ]Strasbourg University Hospital , Strasbourg, France
                Author notes
                [* ]Corresponding author. Tel: +33 1 56 09 37 01, Fax: +33 1 56 09 30 47, Email: jean-yves.le-heuzey@ 123456egp.aphp.fr
                Article
                ehv455
                10.1093/eurheartj/ehv455
                4628644
                26330420
                421f4c9c-dce8-4972-bc3d-0c8c4e3670d8
                © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 29 June 2015
                : 8 August 2015
                : 17 August 2015
                Categories
                FAST TRACK CLINICAL RESEARCH
                ESC Clinical Registry
                Fast Track
                Editor's choice

                Cardiovascular Medicine
                heart failure,sudden death,cardioverter defibrillator,competing risk,cardiac resynchronization

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