Olivier Piot

Cost of care distribution in atrial fibrillation patients: the COCAF study

Abstract Background Atrial fibrillation (AF) currently represents a major economic burden for society. Very few studies have been performed to evaluate the cost of care for AF patients. This study is a large prospective survey designed to analyze the different cost drivers in the treatment of these patients. This survey, named Cost of Care in Atrial Fibrillation (COCAF), evaluated the cost of care for patients with AF treated by cardiologists in general office practice. Methods A group of 671 patients was recruited by 82 cardiologists distributed in all regions of France. The mean age of the patients was 69 years, and 64% were male. The mean follow-up was 329 ± 120 days. The costs of care were analyzed from the health care payer and the societal perspectives. Results During the follow-up period, 21 patients (3.13%) died and 210 (31.3%) patients were hospitalized. The number of hospitalizations and deaths was significantly higher in the group of persistent or permanent AF (PEAF) patients, as compared to paroxysmal AF (PAAF) patients. Hospitalizations were much more frequent in the PEAF group (127) than in the PAAF group (83, P P P P P P P Conclusions This prospective survey shows that hospitalizations represent the major cost driver in the treatment of AF patients. Outpatient care programs must be proposed to AF patients in order to avoid readmissions and to reduce the cost of treatment.

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

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.

Addition of a Second LV Pacing Site in CRT Nonresponders Rationale and Design of the Multicenter Randomized V3 Trial

BACKGROUND Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) in presence of a depressed left ventricular (LV) ejection fraction and a wide QRS complex. It is limited by a high proportion of nonresponders. Attempts have been made, in small studies, to increase the number of stimulation sites to optimize the resynchronization therapy. V(3) is a planned multicenter, randomized trial whose objective is to evaluate the clinical benefit conferred by the addition of a second LV lead in nonresponders after at least 6 months of standard biventricular stimulation. METHODS AND RESULTS A total of 84 patients will be enrolled in 11 French medical centers. Patients will be randomly assigned to receive either an additional LV lead (test group) or to keep their current stimulation system unchanged (control group). Enrollment is planned to begin in March 2010 and is expected to end within 1 year. The primary study end point will be the HF clinical composite score evaluated at 1 year follow-up. Secondary end points include degree of echocardiographic reverse remodeling and changes in clinical measurements. CONCLUSIONS The V(3) trial will examine the clinical benefit conferred by the addition of a second LV lead in nonresponders to standard CRT.

Frequency of Atrial Tachyarrhythmias in Patients Treated by Cardiac Resynchronization (from the Prospective, Multicenter Mona Lisa Study)

The continuous measurement of sustained atrial tachyarrhythmia (AT) is now possible with some permanently implanted devices. Data on this subject remain controversial. The aim of this study was to evaluate the incidence of sustained AT in patients treated with cardiac resynchronization therapy using pacemakers without backup defibrillators (CRT-P), within the first year after implantation, using strict definition criteria for sustained AT and a systematic review of all high-quality electrographically recorded episodes. The Mona Lisa study was a prospective, multicenter, cohort study carried out from February 2004 to February 2006, with a 12-month follow-up period. Sustained AT was defined as an episode lasting > or =5 minutes; episodes were confirmed by a systematic review of electrograms in the whole study population. Of the 198 patients who underwent CRT-P device implantation and were enrolled in the study, 173 were in stable sinus rhythm at baseline and were included in the analysis (mean age 70 +/- 9 years, 66% men, 91% in New York Heart Association class III, mean QRS duration 164 +/- 26 ms, mean left ventricular ejection fraction 25 +/- 7%). During a mean follow-up period of 9.9 +/- 3.6 months, 34 patients experienced > or =1 episode of sustained AT, for an incidence rate of 27.5% (95% confidence interval 18.2 to 36.7). Only a history of AT was independently associated with the occurrence of sustained AT within the 12 months after CRT-P device implantation (hazard ratio 2.3, 95% confidence interval 1.2 to 4.4, p = 0.02). In conclusion, this first prospective electrogram-based evaluation of AT incidence demonstrated that 27% of patients developed > or =1 episode of sustained AT lasting > or =5 minutes in the 12 months after CRT-P device implantation.

Effect of Age on Survival and Causes of Death After Primary Prevention Implantable Cardioverter-Defibrillator Implantation

The benefit of implantable cardioverter-defibrillators (ICDs) remains controversial in elderly patients and may be attenuated by a greater risk of nonarrhythmic death. We examined the effect of age on outcomes after prophylactic ICD implantation. All patients with coronary artery disease or dilated cardiomyopathy implanted with an ICD for primary prevention of sudden cardiac death in 12 French medical centers were included in a retrospective observational study. The 5,534 ICD recipients were divided according to age: 18 to 59 years (n = 2,139), 60 to 74 years (n = 2,693), and ≥75 years (n = 702). Greater prevalences of coronary artery disease and atrial fibrillation at the time of implant were observed with increasing age (both p <0.0001). During a mean follow-up of 3.1 ± 2.0 years, the annual mortality rate increased with age: 3.1% per year for age 18 to 59 years, 5.7% per year for age 60 to 74 years, and 7.5% per year for age ≥75 years (p <0.001). Older age was independently associated with a greater risk of death (adjusted odds ratio 1.43, 95% confidence interval 1.14 to 1.80 for age 60 to 74 years; and adjusted odds ratio 1.65, 95% confidence interval 1.22 to 2.22 for age >75 years). Proportions of cardiac deaths (55.2%, 57.6%, and 57.0%, p = 0.84), including ICD-unresponsive sudden death (9.9%, 6.0%, and 10.6%, p = 0.08), and rates of appropriate ICD therapies were similar in the 3 age groups. Older age was independently associated with a higher rate of early complications and a lower rate of inappropriate therapies. In conclusion, older patients exhibited higher global mortality after ICD implantation for primary prevention, whereas rates of sudden deaths and of appropriate device therapies were similar across age groups.

Safety, feasibility, and outcome results of cardiac resynchronization with triple-site ventricular stimulation compared to conventional cardiac resynchronization

BACKGROUND The nonresponder rate to cardiac resynchronization therapy (CRT) may be due to incomplete resynchronization, with dyssynchrony persisting in approximately 30% of patients. We hypothesized that CRT with triple-site ventricular stimulation (TRIV) may improve resynchronization and its outcomes. OBJECTIVE The purpose of this study was to assess the feasibility and safety of TRIV and collected data on clinical outcomes to dimension future studies. METHODS Our pilot randomized trial was designed to assess the safety and feasibility of TRIV with 2 right ventricular leads and 1 left ventricular leads compared to conventional CRT. The primary end-point was the rate of severe adverse events at 6 months. Secondary end-points included functional improvement parameters, quality-of-life (QOL) score, and changes of echocardiographic indices at 6 and 12 months in a subset of patients. RESULTS Seventy-six patients were enrolled at 11 centers and randomized to control or TRIV arm. All implant procedures but one were successful. At 6 months, there was no statistical difference between proportions of patients with at least 1 severe adverse event in both groups (34.1% vs 25.7%, P = .425). There also was no difference between functional improvement parameters, 6-minute walking distances (P = .40), QOL scores (P = .27), and echographic indices. At 12 months, the proportions of patients with a left ventricular ejection fraction gain of more than 5%, 10%, or 15% were significantly superior with TRIV. CONCLUSION TRIV pacing is an effective and safe technique and may provide a greater benefit in ventricular remodeling than conventional CRT. Further studies are needed to assess its long-term benefit.

Impact of early complications on outcomes in patients with implantable cardioverter-defibrillator for primary prevention

BACKGROUND The lifesaving benefit of implantable cardioverter-defibrillators (ICDs) has been demonstrated. Their use has increased considerably in the past decade, but related complications have become a major concern. OBJECTIVE The purpose of this study was to assess the incidence and effect on outcomes of early (≤30 days) complications after ICD implantation for primary prevention in a large French population. METHODS We analyzed data from 5539 patients from the multicenter French DAI-PP (Défibrillateur Automatique Implantable-Prévention Primaire) registry (2002-2012) who had coronary artery disease or dilated cardiomyopathy and were implanted with an ICD for primary prevention. RESULTS Overall, early complications occurred in 707 patients (13.5%), mainly related to lead dislodgment or hematoma (57%). Independent factors associated with occurrence of early complications were severe renal impairment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.17-2.37, P = .02), age ≥75 years (OR 1.01, 95% CI 1.00-1.02, P = .03), cardiac resynchronization therapy (OR 1.58, 95% CI 1.16-2.17, P = .01), and anticoagulant therapy (OR 1.28, 95% CI 1.02-1.61, P = .03). During a mean ± SD follow-up of 3.1 ± 2.3 years, 824 (15.8%) patients experienced ≥1 late complication (>30 days), and 782 (14.9%) patients died. After adjustment, early complications remained associated with occurrence of late complications (OR 2.15, 95% CI 1.73-2.66, P < .0001) and mortality (OR 1.70, 95% CI 1.34-2.17, P = .003). CONCLUSION Early complications are common after ICD implantation for primary prevention, occurring in 1 in 7 patients, and are associated with an increased risk of late complications and overall mortality. Further studies are needed to investigate the underlying mechanisms of such associations.

Effects of a Selective Al‐Adenosine Receptor Agonist on Heart Rate and Heart Rate Variability During Permanent Atrial Fibrillation

Background: Mean heart rate and irregularity of the rate, i.e., heart rate variability (HRV), are two aspects of heart rate during atrial fibrillation (AF). An important goal of AF therapy is to control mean heart rate during exercise; the determinants of HRV during AF remain poorly known although its prognostic value has been established. Objectives: To investigate the effects of a stable, long‐acting, selective A1‐adenosine receptor agonist, SDZ WAG994, on heart rate during exercise and on HRV. Methods: In a multicenter, double‐blind, randomized, placebo‐controlled, parallel group study, patients with permanent AF performed a symptom‐limited exercise test and underwent 24‐hour ECG monitoring on day 1 during treatment with placebo, and on day 2 during treatment with either placebo or 2 mg SDZWAG994 orally. Changes in mean heart rate during exercise and changes in HRV indices between day 1 and day 2 were compared between the two groups. Results: Thirty‐two patients (64 ± 8 years; 81% male; 25% in NYHA Class II; 38% with no structural heart disease) were included in the study. During active treatments, heart rate remained unchanged at rest and increased significantly during exercise. A significant daytime increase in short‐term HRV indices (DpNN50 = 4.5% P = 0.01; DrMSSD = 6% P = 0.03; DSDNN Index = 6% P = 0.02) occurred during active treatment. Conclusions: Selective A1‐adenosine receptor agonism with SDZ/WAG994 limits the increase in mean heart rate during exercise in patients with AF. In addition, this agonist selectively increases short‐term HRV indices, suggesting that pNN50, rMSSD, and SDNN reflect vagal influences during AF.

Initial and Long-Term Evaluation of Escape Rhythm After Radiofrequency Ablation of the AV Junction in 50 Patients

Between 1986 and 1994, 50 patients (mean age 63 ± 13 years), 25 of whom had organic heart disease and presenting with atrial arrhythmias refractory to 5.6 ± 1.6 antiarrhythmic drugs, underwent radiofrequency ablation (5 ± 3 pulses by procedure; duration of pulses 50.5 ± 32 s) of the proximal AV junction to create complete and permanent AV block. The escape rhythm was studied immediately after the procedure and during long‐term follow‐up. Immediately after the procedure, an escape rhythm was observed in 80% of the patients (junctional in 92%). Over a mean follow‐up of 36 ± 16 months in 47 patients (2 patients died before assessment of escape rhythm and 1 was lost to follow‐up), an escape rhythm was present in 39 patients (83%) and absent in the remaining 8 (17%). The only significant difference between the two groups was the initial presence of an escape rhythm (P = 0.008). However, three patients with an initial escape rhythm had none during long‐term follow‐up. The initial presence of an escape rhythm as a predictive factor of its presence during follow‐up had a sensitivity of 87%, specificity of 63%, positive predictive value of 92%, and negative predictive value of 50%. Thus, the absence of an escape rhythm during long‐term follow‐up causing pacemaker dependency was noted in 1 of 6 patients. This represents a limitation to this palliative treatment, which should be reserved for patients suffering from supraventricular tachycardias refractory to other treatments.

Temporal and Geographical Trends in Indications for Implantation of Cardiac Defibrillators in Europe 1993–1998

Despite the demonstrated efficacy of implantable cardioverter defibrillators (ICDs) in reducing sudden and total mortality in selected populations, their implantation rates vary greatly between countries. The aim of our study was to analyze temporal and geographical trends in ICD implantations in countries with similar health related expenditure in Western Europe. A total of 2,257 patients from ten European evaluation studies of Medtronic defibrillators and defibrillation electrodes, conducted between 1993 and 1998, representing 12 countries, was included in this analysis. Rates of implantation and clinical characteristics were compared between countries and years of implantation. Rates of implantation differed greatly between Western European countries and did not correlate with indices of health related expenditure (i.e., number of patients per physician and number of patients per hospital bed). However, there was a strong and statistically significant negative correlation between the use of amiodarone and the rates of implantation (r =−0.66, P = 0.02). Temporal trends showed a significant increase in the age of the patients receiving an ICD between 1993 and 1998(57 ± 14 vs 61 ± 12years, mean ± SD, P < 0.001). There was also a temporal trend towards an increased incidence of coronary artery disease and a significant decrease in the incidence of cardiomyopathy. There was a temporal increase in implantations in patients with a history of ventricular tachycardia. Despite a general scientific agreement that ICDs are a first line treatment for patients at high risk of sudden cardiac death, their acceptance remains low in several developed countries. This low acceptance may not be entirely related to budget constraint but may also be related to their perceived efficacy by physicians and health authorities.