JACC: HEART FAILURE

VOL. 3, NO. 6, 2015

ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 2213-1779/$36.00

PUBLISHED BY ELSEVIER INC.

http://dx.doi.org/10.1016/j.jchf.2015.01.012

Does Age Influence Cardiac Resynchronization Therapy Use and Outcome? Paul A. Heidenreich, MD, MS,* Vivian Tsai, MD,y Haikun Bao, MS,z Jeptha Curtis, MD,z Mary Goldstein, MD, MS,* Lesley Curtis, PHD,x Adrian Hernandez, MD, MS,x Pamela Peterson, MD, MS,k Mintu P. Turakhia, MD, MAS,* Frederick A. Masoudi, MD, MSk

ABSTRACT OBJECTIVES This study sought to describe the use of CRT-D and its association with survival for older patients. BACKGROUND Many patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) in practice are older than those included in clinical trials. METHODS We 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. RESULTS Receipt 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 ¼ 0.86 for interaction). CONCLUSIONS More 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. (J Am Coll Cardiol HF 2015;3:497–504) © 2015 by the American College of Cardiology Foundation.

C

hronic resynchronization therapy (CRT) has

that of the general population of patients with heart

been shown to improve survival and symp-

failure in the United States. Several studies have

toms for patients with heart failure, re-

found that many patients over age 75 years who

duced ejection fraction, and wide QRS intervals

receive CRT demonstrate improvement in symptoms

(1–5). However, the average age of patients included

and left ventricular ejection fraction (LVEF), howev-

in the trials (mean 62 to 67 years of age) is lower than

er data for a survival benefit have been limited to

From the *Veterans Administration Palo Alto Healthcare System, Palo Alto, California; yPalo Alto Medical Foundation, Palo Alto, California; zDepartment of Medicine, Yale School of Medicine, New Haven, Connecticut; xDuke Clinical Research Institute, Durham, North Carolina; and the kUniversity of Colorado Anschutz Medical Campus, Aurora, Colorado. Dr. Heidenreich is supported by a grant from Veterans Administration Quality Enhancement and Research Initiative 04-326. Dr. Turakhia is supported by Veterans Health Services Research and Development Career Development Award CDA09027-1. Dr. Peterson is supported by Agency for Healthcare Research and Quality grant K08 HS019814-01. Dr. Curtis owns stock in Medtronics; and has received grant support from Boston Scientific through her institution. Dr. Hernandez has received grant support from Medtronics-Research. Dr. Turakhia has received grant support from Medtronics, iRhythm, Gilead Sciences; is an employee of U.S. Department of Veterans Affairs; has consulted for Medtronic, St. Jude Medical, and Precision Health Economics; and has received lecture honoraria from Biotronik. Dr. Masoudi is senior medical officer for American College of Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received September 22, 2014; revised manuscript received January 1, 2015, accepted January 9, 2015.

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Heidenreich et al.

JACC: HEART FAILURE VOL. 3, NO. 6, 2015 JUNE 2015:497–504

Age, CRT Use, and Outcome

ABBREVIATIONS

subgroups of randomized trials, which were

with those who did not, using the chi-square test

AND ACRONYMS

small in size (6).

for categorical variables and unbalanced Student

We sought to describe the use of CRT with

t test for continuous variables. Two variables with

defibrillator (CRT-D) among older patients

missing values of more than 5% (B-type natriuretic

in the United States. We used data from the

peptide level and PR interval) were excluded from

resynchronization therapy with

National

Registry

the primary analyses. Variables with low missing

defibrillator

(NCDR) ICD registry to determine how often

rates were imputed as the most common category

CRT-P = cardiac

older candidates for a CRT and an implant-

for the categorical variables and the median value

resynchronization therapy with

able cardioverter-defibrillator (ICD) receive

for continuous variables. For categorical variable

CRT-D or only an ICD. We also sought to

with a missing rate >5%, a category was added

determine the difference in outcome for US

to indicate “missingness.” The multiple logistic

older patients receiving CRT-D compared to

regression model was used to examine associations

fraction

ICD alone among those who were candidates

between patients, hospitals, and physicians’ charac-

NCDR = National

for CRT.

teristics and the use of CRT-D, and a forward step-

CRT = cardiac resynchronization therapy

CRT-D = cardiac

pacing and no defibrillator

ICD = implantable cardioverter-defibrillator

LVEF = left ventricular ejection

Cardiovascular

Disease

wise selection method (entry p value of 0.05 and

Cardiovascular Disease Registry

NYHA = New York Heart

METHODS

retention p value of 0.05) was used to identify

Association

variables most strongly associated with the use of DATA SOURCE. We used data from the NCDR-ICD

CRT-D. Cox proportional hazard models were used

registry, created in 2006 through a mandate from

to explore the impact of CRT-D use on survival

the Centers of Medicare and Medicaid Services (CMS),

among different age groups, with adjustment of

which requires all hospitals to report data for ICD

patient, hospital, and physician’s characteristics.

implantations for primary prevention (7). Although

For multivariable analyses, we used the presence of

hospitals are required to enter data only for Medicare

ischemic heart disease (yes/no) to indicate cause of

beneficiaries, most institutions register all ICD im-

heart failure. All analyses were performed with SAS

plantations. Institutions use a standardized ques-

version 9.2 software (SAS Institute, Cary, North

tionnaire to enter clinical data including patient

Carolina). All analyses were approved by the Yale

clinical characteristics, device used, other treat-

University Human Investigation Committee.

ments, and hospital outcome. Data are subjected to quality control checks for missing and improperly

RESULTS

coded items, and a random audit is conducted annually through site visits (8).

PATIENT CHARACTERISTICS. Patient characteristics

of the 70,854 patients included in the analysis are SEE PAGE 505

listed in Table 1 with groupings by age. Mean age was 69 years, and 69% were male. Those 75 years of age or

PATIENTS. We identified patients who were candi-

older (n ¼ 27,359) accounted for 39% of those un-

dates for CRT (QRS $120 ms, LVEF #35%, New York

dergoing ICD placement. Although most of the dif-

Heart Association [NYHA] functional class III or IV,

ferences were statistically significant due in part to

and had their first ICD implanted at a facility report-

the large sample size, not all were clinically relevant.

ing for Medicare and non-Medicare patients. Of these

Older patients were more likely to be non-Hispanic

patients, we included 72,563 after excluding patients

white compared to younger age groups. Ischemia, as

with previously implanted pacemakers (16,640) and

the cause of cardiomyopathy, increased with age as

previous cardiac arrest (9,993) and cardiac trans-

did LVEF (although the mean LVEF was