Methods

As previously reported, since March 2004, 117 Italian cardiology centers have inserted all consecutive patients receiving Medtronic (Minneapolis, Minnesota) implantable cardiac devices in the ClinicalService Project. Data are collected prospectively and may be mined for observational research. An independent physician steering committee identifies key clinical questions on a yearly basis for analysis and publication. The project was approved by each site’s Institutional Review Board or Medical Director and conformed to the principles outlined in the Declaration of Helsinki. Each patient provided written informed consent for data collection and analysis.

We evaluated all patients who received an ICD or a cardiac resynchronization therapy (CRT) device with defibrillator capabilities (CRT-D) between May 2004 and May 2011. Indication for a defibrillator implantation was based on the current guidelines, after optimization of medical therapy, as recommended by the American College of Cardiology/American Heart Association Heart Failure Guidelines. Baseline demographic, clinical, and functional data, a standard electrocardiogram, an echocardiogram, and information on drug therapy were collected for each subject. Follow-up examinations were scheduled according to the clinical practice of each center; therefore, they might have varied in function of the implanted device and clinical conditions. At each follow-up visit, the ICD or CRT-D was interrogated and checked for appropriate functioning, and information on clinical conditions was collected. Mortality data were obtained through telephone interviews to relatives and the treating physician; where possible, the information was validated by consulting medical records.

The primary objective of the study was to evaluate the effect of age on mortality in patients with ICD, and the clinical factors modulating the age-mortality association. Secondarily, we wanted to verify the existence of age-related differences in prognostic predictors.

Patient population was stratified into 3 age groups (<65, 65 to 74, and ≥75 years).

To further analyze the influence of aging on survival rates, we used the MADIT-II score, a tool combining readily available clinical variables indicating the presence of an advanced degree of disease and co-morbidities. The instrument proved effective in identifying ICD recipients at high risk of mortality during follow-up and has already been used for evaluation of a geriatric population. In its original version, one point is assigned for each of the following conditions: the New York Heart Association (NYHA) class >2, age ≥70 years, blood urea nitrogen (BUN) >26 mg/dl, QRS duration >0.12 seconds, and the presence of atrial fibrillation.

Statistical analysis was performed using SAS 9.3 for Windows (SAS Inst. Inc., Cary, North Carolina). Continuous variables are expressed as mean ± SD; twenty-fifth and seventy-fifth percentiles were used to describe the follow-up period. Categorical variables are expressed as raw data and percentages. Different distributions of baseline characteristics were assessed using analysis of variance or chi-square test for continuous or categorical variables, respectively. In univariate analysis, given the large sample size and the existence of the 3 different age groups, statistical significance was attributed for 2-tailed p values <0.017. Survival rates (number of deaths over time) were computed per 100 person-years together with the 95% confidence intervals (95% CIs), and subsequently, compared by means of mixed Poisson models. All-cause mortality was studied using Kaplan-Meier curves and was compared among the groups by means of the log-rank test. Cox regression analysis was performed in univariate models. This allowed reporting the results as hazard ratio (HR) with the related 95% CI. All variables significantly associated with prognosis were introduced into a Cox regression model to identify independent predictors of all-cause mortality. The proportional hazard assumptions were tested by means of Schoenfeld residuals. The presence of a CRT device did not meet the proportional hazard assumption for mortality. Hence, we could not explore the independent weight of the resynchronization therapy on the survival rate in the general model. Consequently, through 2 further Cox regression models, we assessed the effect of age group on mortality in patients with and without CRT. To verify the weight of different clinical predictors of prognosis in subjects aged <65, 65 to 74, and ≥75 years, 3 separate multivariate models, 1 for each age group, were evaluated. In these cases, age was entered as a continuous variable. Finally, on the basis of the demographic composition and the statistical distribution of our population, patients were classified according to the MADIT-II score as at low, intermediate, or high risk for scores ≤1, 2, or >2, respectively. Given that the collection of BUN values was not mandatory, we arbitrarily substituted the variable with the presence of chronic renal failure, condition assigned by each center on the basis of the existing guidelines. For survival rate models and analysis of the MADIT-II score, a 2-tailed p value <0.05 was considered statistically significant.

Results

Of 6,311 patients with ICD, 1,510 (23.9%) were aged ≥75 years. Patients implanted with a CRT-D device were 4,212 (66.7%). Patients’ baseline characteristics are listed in Table 1 . The proportion of men did not vary with age. The prevalence of the most important HF co-morbidities significantly increased in the elderly and in the very elderly, and coronary artery disease (CAD) emerged as the most frequent cause of HF at an advanced age. Left ventricular ejection fraction (LVEF) was similar in all age groups, but very elderly subjects showed lower left ventricular volumes, longer QRS duration, and a more compromised functional profile, as evaluated by the NYHA class. With age, use of β blockers progressively decreased, whereas the use of diuretics and amiodarone increased. In coherence with the age-related correlation between CAD and HF, antiplatelet therapy was more frequent in subjects ≥75 years of age. CRT was more common in elderly and very elderly patients ( Table 1 ).

During a median follow-up of 27 months (twenty-fifth to seventy-fifth percentile: 14 to 44 months; on the whole, 16,165 person-years), 685 patients died (4.2 events per 100 person-years, 95% CI 3.9 to 4.6). All-cause mortality was significantly higher in old and very old patients (p <0.001) ( Figure 1 ). Apart from age, univariate analysis showed that male gender, number of hospitalizations, atrial fibrillation, complex sustained ventricular arrhythmias, and co-morbidity were all directly correlated with adverse prognosis. With regard to drug therapy, β blockers appeared to be associated with a protective role on the mortality, whereas diuretics appeared to be associated with an unfavorable outcome ( Table 2 ). Multivariate Cox regression analysis showed that CAD, chronic obstructive pulmonary disease (COPD), diabetes, chronic renal failure, and the presence of ventricular arrhythmias were independent predictors of increased mortality, whereas higher LVEF proved protective ( Table 2 ). After adjustment, the HR value for mortality by age group decreased from 1.65 to 1.58. This result suggests that 22.6% of events in subjects ≥75 years, when compared with those <65 years, could be explained by confounding clinical factors ( Table 2 ). Two Cox multivariate models evidenced that the weight of age group on prognosis was significant both in patients with (HR 1.50, p <0.001) and without (HR 1.86, p <0.001) a CRT device.

Kaplan-Meier analysis of all-cause mortality after ICD implantation by age group. The gray area surrounding the curves delimits the 95% confidence band. At risk table is reported above the x-axis.

The 3 different multivariate models analyzing the predictors of mortality for each age group demonstrated that (1) for patients <65 years, only cardiologic variables affected the outcome, (2) for patients aged 65 to 74 years, prognosis was influenced by age, cardiologic variables, and the presence of renal failure, and (3) for patients ≥75 years, age alone exerted a significant influence on the mortality ( Table 3 ).

Table 3

Clinical predictors of mortality by age group. Results of the Cox regression analysis

a. Univariate Analysis	Age <65 yrs (n = 2,470)			Age 65–74 yrs (n = 2,331)			Age ≥75 yrs (n = 1,510)
	HR	95% CI	p Value	HR	95% CI	p Value	HR	95% CI	p Value
Age (delta·yrs)	1.05	1.02–1.07	<0.001	1.05	1.01–1.10	0.016	1.10	1.05–1.15	<0.001
Gender (men vs women)	1.41	0.89–2.23	0.14	1.52	1.05–2.21	0.028	1.36	0.94–1.98	0.10
AF (yes vs no)	2.28	1.47–3.56	<0.001	1.26	0.90–1.76	0.17	1.33	0.95–1.85	0.094
CAD (yes vs no)	1.92	1.40–2.62	<0.001	1.53	1.19–1.97	<0.001	1.21	0.92–1.59	0.18
Chronic obstructive pulmonary disease (yes vs no)	2.18	1.31–3.64	0.003	1.74	1.24–2.44	0.001	1.54	1.08–2.19	0.016
Diabetes mellitus (yes vs no)	1.57	1.08–2.27	0.018	1.48	1.13–1.9	0.004	1.15	0.83–1.59	0.40
Hypertension (yes vs no)	1.06	0.75–1.51	0.74	1.03	0.78–1.35	0.85	0.95	0.71–1.28	0.74
Renal failure (yes vs no)	2.07	1.16–3.68	0.014	2.25	1.58–3.20	<0.001	1.71	1.18–2.49	0.005
Valvular diseases (yes vs no)	0.93	0.58–1.48	0.75	1.01	0.72–1.42	<0.001	1.00	0.67–1.49	1.00
Ventricular arrhythmias (yes vs no)	1.12	0.82–1.52	0.48	1.37	1.07–1.74	0.012	1.18	0.90–1.54	0.24
Left ventricular end-diastolic volume (delta·ml)	1.00	1.00–1.00	0.011	1.00	1.00–1.00	0.39	1.00	1.00–1.00	0.51
Left ventricular end-systolic volume (delta·ml)	1.00	1.00–1.00	0.24	1.00	1.00–1.00	0.022	1.00	1.00–1.01	0.17
LVEF (delta·%)	0.97	0.95–0.99	<0.001	0.96	0.94–0.97	<0.001	0.98	0.96–1.00	0.015
QRS length (delta·ms)	1.00	1.00–1.00	0.096	1.00	1.00–1.00	0.94	1.00	1.00–1.00	0.61
NYHA (III to IV vs I to II)	1.98	1.45–2.71	<0.001	1.71	1.32–2.21	<0.001	1.22	0.92–1.60	0.17

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients With Suspected Acute Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial)
2. Effects of Angiotensin-Converting Enzyme Inhibitors and Beta Blockers on Clinical Outcomes in Patients With and Without Coronary Artery Obstructions at Angiography (from a Register-Based Cohort Study on Acute Coronary Syndromes)
3. Relation of Left Atrial Dysfunction to Ischemic Stroke in Patients With Coronary Heart Disease (from the Heart and Soul Study)
4. Yield of Noncardiac Biopsy for the Diagnosis of Transthyretin Cardiac Amyloidosis

Stay updated, free articles. Join our Telegram channel

Join