Author + information
- William Escande, MD,
- Serge Boveda, MD,
- Pascal Defaye, MD,
- Christophe Leclercq, MD, PhD,
- Nicolas Sadoul, MD, PhD,
- Marie-Cecile Perier, PhD,
- Jean-Claude Deharo, MD, PhD,
- Laurent Fauchier, MD, PhD,
- Eloi Marijon, MD, PhD,
- Olivier Piot, MD∗ (, )
- on behalf of the DAI-PP Investigators
- ↵∗Centre Cardiologique du Nord, 32-36 Rue des Moulins Gémeaux, 93200 Saint-Denis, France
In the setting of primary prevention of sudden cardiac death, international guidelines (1) recommend an implantable cardioverter-defibrillator (ICD) for symptomatic patients (New York Heart Association [NYHA] functional class II or III) with altered left ventricular ejection fraction (LVEF) (≤35%). Our objective was to compare outcomes among patients implanted with a primary prevention ICD according to whether the implantations were guideline-based or not.
The DAI-PP (Primary Prevention ICD French Registry) (NCT01992458) enrolled all consecutive patients with ischemic or dilated cardiomyopathy implanted with a primary prevention ICD in 12 French centers between 2002 and 2012 (2). On-guideline patients met both basic criteria, namely, LVEF ≤35% and NYHA functional class II to III. Off-guideline patients did not meet at least 1 of the 2 criteria. We focused on candidates without an indication for cardiac resynchronization therapy. Vital status and causes of death were ascertained by review of hospital medical files or by communication with primary care physicians, and were corroborated with the French vital status database of the National Institute of Economic Statistics and the French Center on Medical Causes of Death. ICD programming was nonstandardized, although there was a broad consensus between centers (all except 1) concerning the use of high ventricular rates and usually 2 zones (typically ventricular tachycardia >180 beats/min, ventricular fibrillation >220 beats/min). All data were analyzed using the SAS program version 9.4 (SAS Institute, Cary, North Carolina).
Of a total of 5,539 patients enrolled in DAI-PP study, 2,538 were implanted with a single- or double-chamber ICD. Mean age was 60.2 ± 11.7 years, 1,694 (87.4%) were men, 1,379 (71.9%) had ischemic cardiomyopathy, mean LVEF was 28.2 ± 8.6%, and 853 (59.3%) had a QRS width <120 ms. Guideline eligibility for implantation could be eventually ascertained in 1,939 patients (76.4%). Overall, 500 patients (25.8%) were identified to be implanted off-guideline, with a mean LVEF about 33.8 ± 12.7% and with 418 (83.6%) having an NYHA functional class I or IV.
We observed no significant intergroup differences in age, sex, type of cardiomyopathy, type of ICD, and sinus rhythm. Over time, the proportion of off-guideline patients remained unchanged (p = 0.48). On-guideline patients had a sicker clinical profile with a lower mean LVEF (26.3 ± 5.4% vs. 33.8 ± 12.7% for on-guideline vs. off-guideline patients, respectively; p < 0.0001), a higher proportion of QRS width >150 ms (16.0% vs. 10.7%; p = 0.01), a higher prevalence of renal (glomerular filtration rate <30 ml/min in 9.1% vs. 4.1%; p = 0.002), and respiratory (12.2% vs. 7.6%; p = 0.009) failures. Off-guideline patients had a higher proportion of nonsustained ventricular tachycardia on pre-implantation Holter monitoring (29.3% vs. 23.9%; p = 0.03).
After a mean follow-up of 3.1 ± 2.2 years (completed in 98.4%), on-guideline patients had a higher annual incidence of overall mortality compared with off-guideline patients (incidence rate ratio: 1.85; 95% confidence interval [CI]: 1.32 to 2.60; p = 0.0003) (Figure 1, top). In a multivariable prediction model adjusted by age, sex, guidelines status, perioperative complications, number of comorbidities, and period of implantation, on-guideline status (odds ratio: 2.67; 95% CI: 1.76 to 4.05) and age (odds ratio: 1.05; 95% CI: 1.03 to 1.06) remained associated with overall mortality.
Interestingly, frequencies of appropriate therapies (antitachycardia pacing and/or shock) were similar among on- and off-guideline patients (Figure 1, bottom), with annual incidences of 72.53 (95% CI: 63.66 to 81.40) and 76.22 (95% CI: 61.05 to 91.38) per 1,000 person-years, respectively (incidence rate ratio: 0.95; 95% CI: 0.75 to 1.20; p = 0.55). No variable independently predicted the occurrence of appropriate ICD therapies.
In this large cohort of primary prevention ICD recipients, more than one-quarter were implanted without fulfilling proper guideline criteria, similar to rates reported in other large registries (3). Despite a less severe clinical profile at implantation and lower mortality rates, off-guideline patients had, rather surprisingly, similar rates of appropriate therapies. These patients were equally likely to benefit from their ICDs. The criteria of LVEF and NYHA functional class as proposed in the current guidelines may not be absolute or exclusive predictors of high arrhythmic risk. The excess mortality for on-guideline patients in this study may be explained by the competing risk of nonarrhythmic death (4,5).
Please note: The DAI-PP registry was funded by the French Institute of Health and Medical Research, the ART (Association de Rythmologie Toulousaine), and the French Society of Cardiology. Dr. Boveda has served as a consultant for Medtronic, Boston Scientific, and LivaNova. Dr. Sadoul has served as a consultant for Boston Scientific, Biotronik, Medtronic, LivaNova, and St. Jude Medical. Dr. Piot has served as a consultant for Medtronic, Abbott, Boston Scientific, and LivaNova. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Primary Prevention ICD French Registry [DAI-PP]; NCT01992458)
- 2017 American College of Cardiology Foundation
- Yancy C.W.,
- Jessup M.,
- Bozkurt B.,
- et al.
- Escande W.,
- Marijon E.,
- Defaye P.,
- et al.
- Goldenberg I.,
- Vyas A.K.,
- Hall W.J.,
- et al.