16-Year Trends in the Infection Burden for Pacemakers and Implantable Cardioverter-Defibrillators in the United States

Article (PDF Available)inJournal of the American College of Cardiology 58(10):1001-6 · August 2011with41 Reads
DOI: 10.1016/j.jacc.2011.04.033 · Source: PubMed
Abstract
We analyzed the infection burden associated with the implantation of cardiac implantable electrophysiological devices (CIEDs) in the United States for the years 1993 to 2008. Recent data suggest that the rate of infection following CIED implantation may be increasing. The Nationwide Inpatient Sample (NIS) discharge records were queried between 1993 and 2008 using the 9th Revision of the International Classification of Diseases (ICD-9-CM). CIED infection was defined as either: 1) ICD-9 code for device-related infection (996.61) and any CIED procedure or removal code; or 2) CIED procedure code along with systemic infection. Patient health profile was evaluated by coding for renal failure, heart failure, respiratory failure, and diabetes mellitus. The infection burden and patient health profile were calculated for each year, and linear regression was used to test for changes over time. During the study period (1993 to 2008), the incidence of CIED infection was 1.61%. The annual rate of infections remained constant until 2004, when a marked increase was observed, which coincided with an increase in the incidence of major comorbidities. This was associated with a marked increase in mortality and in-hospital financial charges. The infection burden associated with CIED implantation is increasing over time and is associated with prolonged hospital stays and high financial costs.
omas Jeerson University
Jeerson Digital Commons
Department of Medicine Faculty Papers Department of Medicine
8-30-2011
16-year trends in the infection burden for
pacemakers and implantable cardioverter-
debrillators in the United States 1993 to 2008.
Arnold J Greenspon
omas Jeerson University, arnold.greenspon@jeerson.edu
Jasmine D Patel
Drexel University
Edmund Lau
Drexel University
Jorge A Ochoa
Drexel University
Daniel R Frisch
omas Jeerson University
See next page for additional authors
Follow this and additional works at: hp://jdc.jeerson.edu/medfp
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Recommended Citation
Greenspon, Arnold J; Patel, Jasmine D; Lau, Edmund; Ochoa, Jorge A; Frisch, Daniel R; Ho,
Reginald T; Pavri, Behzad B; and Kurtz, Steven M, "16-year trends in the infection burden for
pacemakers and implantable cardioverter-debrillators in the United States 1993 to 2008." (2011).
Department of Medicine Faculty Papers. Paper 60.
hp://jdc.jeerson.edu/medfp/60
Authors
Arnold J Greenspon, Jasmine D Patel, Edmund Lau, Jorge A Ochoa, Daniel R Frisch, Reginald T Ho, Behzad
B Pavri, and Steven M Kurtz
is article is available at Jeerson Digital Commons: hp://jdc.jeerson.edu/medfp/60
As submitted to:
Journal of the American College of Cardiology
And later published as:
Sixteen Year Trends in the Infection Burden for Pacemakers and
Implantable Cardioverter-Defibrillators in the United States: 1993-2008
doi:10.1016/j.jacc.2011.04.033
Volume: 58, Issue: 10, Pages: 1001-1006, 2011
Arnold J. Greenspon M.D.
FACC
1
, Jasmine D. Patel PhD
2,3
, Edmund Lau MS
2,3
, Jorge
Ochoa PhD
3
, Daniel Frisch M.D. FACC
1
, Reginald Ho M.D. FACC
1
, Behzad Pavri M.D.
FACC
1
, Steven Kurtz
PhD
2,3
1
Thomas Jefferson University Hospital, Philadelphia, PA
2
Drexel University, Philadelphia, PA
3
Exponent, Philadelphia, PA
Key words
: endocarditis, infection, pacemakers, ICDs.
Word count-
Title=17, Text (including abstract) = 1896, References= 525, Figure Legends= 53
Total=2491
Running Title:
Infection Trends for Pacemakers and ICDs
Address for correspondence:
Arnold J. Greenspon M.D. FACC
Jefferson Heart Institute
925 Chestnut Street, Mezzanine
Philadelphia, PA 19107
215-955-8659
Email: arnold.greenspon@jefferson.edu
Field Code Changed
Abstract
Objectives: We analyzed the infection burden associated with the implantation of
cardiac implantable electrophysiologic devices (CIED) in the United States for the years 1993-
2008.
Background: Recent data suggests that the rate of infection following CIED
implantation may be increasing.
Methods: The Nationwide Inpatient Sample (NIS) discharge records were queried
between 1993-2008 using the 9th Revision of the International Classification of Diseases (ICD-
9-CM). CIED infection was defined as either: (1) ICD-9 code for device related infection
(996.61) and any CIED procedure or removal code, or (2) CIED procedure code along with
systemic infection. Patient health profile was evaluated by coding for renal failure, heart failure,
respiratory failure, and diabetes mellitus. The infection burden and patient health profile were
calculated for each year and linear regression was used to test for changes over time.
Results: During the study period (1993-2008), the incidence of CIED infection was
1.61%. The annual rate of infections remained constant until 2004 when a marked increase was
observed, which coincided with an increase in the incidence of major co-morbidities. This was
associated with a marked increase in mortality and in-hospital charges.
Conclusions: The infection burden associated with CIED implantation is increasing over
time and is associated with prolonged hospital stays and high financial costs.
Abbreviations:
PM= Permanent pacemaker
ICD= Implantable cardioverter defibrillator
CIED= Cardiac implantable electrophysiologic device
ICD-9= 9
th
Revision of the International Classification of Diseases
NIS= National In-Patient Sample
CRT= Cardiac resynchronization therapy
Introduction
Implantation of cardiac implantable electrophysiology devices (CIED) which include permanent
pacemakers (PM) and implantable cardioverter defibrillators (ICDs) has dramatically increased
over the past several years.
1,2,3
This is largely due to the expanded indications for CIED
implantation based on the results of large clinical trials of ICDs for primary prevention as well as
the aging of the general population.
4,5,6
Infection associated with CIEDs is a serious
complication with high morbidity and mortality.
7,8,9
Previous studies have suggested that the
number of infections associated with CIED is increasing.
10,11
We sought to analyze the historical
trends for CIED infection in the United States over
sixteen years and evaluate the implications of
these trends.
Methods
The Nationwide Inpatient Sample (NIS) discharge records were queried to identify
demographic (e.g., age, gender), health profile/risk (incidence and severity of comorbidities,
mortality) and health economic (length of stay, procedural costs and charges) data for PM and
ICD patients between 1993-2008 using the 9th Revision of the International Classification of
Diseases (ICD-9-CM). Specifically, procedures were identified by the ICD-9-CM codes that
identified both primary and revision CIED procedures: Primary PM: 37.80-83, 00.50; Primary
ICD: 37.94, 37.96, 00.51; PM Removal: 37.79, 37.85-87, 37.89, 00.53; ICD Removal: 37.98,
00.54. Revision procedures include pulse generator replacement as well as device upgrades to
either dual chamber or cardiac resynchronization therapy (CRT) devices. During this time
period, the ICD-9-CM codes for these procedures have been consistent, thereby allowing the
analysis of longitudinal trends in the data for prevalence of device implantation.
Patients with a CIED-related infection, either pocket infection or systemic infection
including lead-associated endocarditis, were identified in one of two ways: (1) an ICD-9
diagnosis code for device related infection (996.61) along with any CIED primary procedure or
removal code, or (2) a CIED device removal code (37.77, 37.7, 37.89, 37.99) along with
evidence of systemic infection such as sepsis (038 or 785.59), bacteremia (790.7) or fever
(780.6). Patient health profile was evaluated by coding for renal failure, heart failure, respiratory
failure, and diabetes mellitus.
Deleted:
the past 15
The CIED infection burden was calculated by dividing the number of device related
infections by the corresponding number of primary or revision procedures. Analyses of the NIS
records with the relevant surgical codes were conducted using SAS (Version 9.2). The sampling
weights and the stratified sampling design of the NIS were taken into consideration when
computing summary statistics and standard errors of these estimates. The number of surgeries
performed for a particular demographic group is a positive integer and is assumed to follow a
Poisson distribution. A regression model was used to estimate the surgery and infection rate, and
normalized by the size of the population, and evaluation of the calendar year trend. The surgery
rate was adjusted by age, sex, race, and census regions to accommodate differences in the
prevalence among demographic subpopulations. The infection burden and patient health profile
were calculated for each year and linear regression was used to test for changes over time.
Results
Trends in CIED infection
Between 1993 and 2008, over 4.2 million primary implantations of PM (3,204,700
records) and ICD (1,124,000 records) were identified using ICD-9-CM procedure codes. We
found that the incidence of CIED implantation increased an average of 4.7% annually and the
overall CIED implantation increased by 96% from 1993-2008 (Figure 1). The majority of this
increase was due to the large increase in ICD implantation (504%) as pacemaker implantation
increased by 45% during this time period. By 2008, ICDs represented 35% of all CIED
implantations (Figure 2).
During the study period (1993-2008), approximately 69,000 patients were treated for
CIED infection (incidence= 1.61%). The incidence of infection increased by 210% from 2660
cases in 1993 to 8230 cases in 2008. The annual rate of infections remained fairly constant until
2004 when a marked increase was observed. The rate of infection increased significantly from
1.53% in 2004 to 2.41% in 2008 (p<0.001) (Figure 3).
The rates of CIED infection from 1993-2008, categorized by patient demographics (age,
gender, race), showed that the highest infection rates occurred in white (82%), male (67%)
patients over the age of 65 (64%). (Figure 4).
Role of comorbidities in CIED infection
The incidence of four major comorbidities (renal failure, respiratory failure, heart failure and
diabetes) in patients with CIED infection remained fairly constant from 1993 through 2004 when
a marked increase was observed (Figure 5). In addition, the risk of mortality significantly
increased in patients with respiratory failure (odds ratio = 13.58; 95% CI 12.88-14.3), renal
failure (odds ratio = 4.28; 95% CI 4.04-4.53), heart failure (odds ratio = 2.71; 95% CI 2.54-2.88)
but decreased slightly in patients with diabetes (odds ratio = 0.91; 95% CI 0.86-0.96) (p<0.001).
Financial burden and mortality rates associated with CIED infection
In 1993, in-hospital charges for CIED infection were approximately $75,000 and
increased to over $146,000 by 2008, an increase of 47% per decade (Figure 6). In-patient
mortality associated with CIED infection averaged 4.39%, but increased from 2.91% in 1993 to
4.69% in 2008, representing an increase of 1% per decade. During the study period
hospitalization remained constant and averaged 13.8 days.
Discussion
An analysis of the Nationwide Inpatient Sample (NIS) demonstrates that during the study
period 1993-2008, the national CIED infection burden has increased. Specifically, there has
been an increase in the incidence of CIED infection along with an increase in inpatient mortality.
Current patients have a high number of clinical comorbidities associated with prolonged hospital
stays and an increase in the utilization of medical resources reflected by an increase in hospital
charges.
Over the past 20 years, the number of patients with CIEDs has dramatically increased.
1,2,3
Among Medicare beneficiaries, the rate of cardiac device implantation increased by 42%
between 1990-1999.
10
Our initial analysis of NIS data
1
, which included patients with all types
of insurance coverage, showed a 30% increase in the primary pacemaker implantation rate of
50.0 per 100,000 persons of population in 1993 to 65.1 per 100,000 in 2006. ICD implantation
rate increased more rapidly during this period of time. In 1993, the ICD implantation rate was
6.1 per 100,000 persons of population and rose dramatically to 46.2 per 100,000 persons of
population by 2006, an increase of over 500%.
The present study demonstrates that overall CIED implantation increased by 96%. Most
of this increase was due to the marked increase in ICD utilization. By the end of the study
period, ICDs represented 35% of all devices. It is estimated that CIED device utilization will
continue to grow over the next several years due to expanded Medicare coverage for these
devices.
12
Complications of CIED implantation are an important consideration in patient
selection for CIED implantation. Interestingly, immediate post procedural complications related
to CIED implantation have decreased. Al-Khatib and co-workers reported that the rate of post
procedural complications in CIED recipients fell between 2002-2005.
13
The fall in procedure
related complications may be due to operator experience, improved device technology, and
patient selection.
13,14,15
Unfortunately, the corresponding risk of device-related infection has not
changed during the same period of time.
8,11, 11,16
,
17
Previous studies have attempted to define the burden of CIED infection. Voigt and
colleagues analyzed records from the National Hospital Discharge Survey (NHDS) between
1996 and 2006.
11
Analysis of the NHDS database showed that device related infection in CIED
patients increased out of proportion to the overall increase in device utilization during the period
1996-2006. The NIS database, analyzed in the present study, samples about 25 times more
discharge records than the NHDS and tends to sample data from larger institutions. This may
account for some variation between the two surveys.
Results from our analysis of the NIS show that the annual incidence of CIED infection
increased by 210% to 2.41% in 2008 (p<0.0001). Our data may more accurately reflect the true
CIED infection burden since previous studies may have included patients with infections of other
cardiac devices such as prosthetic heart valves and not CIED alone. We required a CIED
procedure code along with the 996.61 code to define a CIED infection. We also defined a device
related infection as evidence of sepsis or bacteremia along with a CIED removal code. This
study and others highlight the disturbing trend of increasing CIED infection.
10,11,10,11,16,16
CIED infection is associated with high patient morbidity and a mortality rate of up to
18%.
Error! Bookmark not defined.9,8,9,16
The financial burden of CIED infection is reflected by the 47% per
decade increase in hospital charges related to CIED infection. By 2008, hospital charges were
over $146,000. These expenditures do not include the additional costs of prolonged recovery
and rehabilitation following treatment of the infection. Therefore, CIED infection has enormous
economic implications.
18
The reason for the increasing rate of CIED infection despite a decrease in overall device
related complications is not clear. One possibility for this observation includes the increasing
numbers of ICD and CRT devices whose longevity is significantly lower than PM. It is
estimated that over 70% of ICD recipients will require device replacement surgery.
19
Device
replacement surgery is associated with an increased risk of infection.
19,20
There may be an
increasing burden of device replacements in the overall CIED population since ICDs now
represent 35% of all implantations.
Patient characteristics, in addition to replacement burden, likely contribute to the
increasing infection burden. It is well known that patients with chronic renal insufficiency and
diabetes mellitus are at particular risk for CIED infection.
21
Our analysis showed that there is an
increasing incidence of these risk factors in CIED patients. While the present study shows that
the incidence of comorbidities in patients who present with CIED infection is increasing it does
not address the important question of what specific risk factors predict CIED infection or what
factors might mitigate this issue. However, it does appear that patients with multiple
comorbidities are at particular risk. Further study of these critical issues is important.
In summary, the infection burden associated with CIED implantation is increasing over
time. This is likely due to expanding ICD indications and the increasing comorbidities in the
CIED population. Infection is associated with prolonged hospital stays and high financial costs.
Further investigation into the risk factors for CIED infection is warranted.
Figure 1. Annual Number of PM and ICD Implantations: 1993-2008
Figure 2. PMs and ICDs as a percentage of all CIED implantations: 1993 vs 2008
Figure 3. Rate of CIED infection.
Figure 4. Distribution of CIED infection based on patient age.
Figure 5. Incidence of comorbidities in patients with CIED infection
Figure 6. In-hospital charges associated with CIED infection (inflation adjusted to $2009)
2
4
6
8
,0
10
Hospi
tal Charges
($)
1
Kurtz SM, Ochoa JA, Lau E, et al: Implantation trends and patient profiles for pacemakers and implantable
cardioverter defibrillators in the United States: 1993-2006. Pacing Clin Electrophysiol 2010;33:705-711
2
Mond HG, Irwin M, Ector H, Proclemer A. The world survey of cardiac pacing and cardioverter defibrillators:
Calendar year and Electrophysiology 2005- an International Cardiac Pacing and Electrophysiology Society (ICPES)
project. Pacing Clin Electrophysiol 2008;31:1202-1212
3
Uslan DZ, Tleyjeh IM, Baddour LM, St Sauver JL, Hayes DL: Temporal trends in permanent pacemaker
implantation: A population study. Am Heart J: 2008;155:896-903
4
Myerburg RJ: Implantable cardioverter-defibrillators after myocardial infarction. N Eng J Med 2008;359:2245-
2253
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Bardy GH, Lee KL, Mark DB, et al.: Sudden cardiac death in heart failure trial (SCD-HeFT). Amiodarone or an
implantable defibrillator for congestive heart failure. N Eng J Med 2005;352:225-237
6
Moss AJ, Zareba W, Hall WJ et al.: Multicenter Automatic Defibrillator Implantation Trial II Investigators.
Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N
Eng J Med 2002;346:877-883
7
Darouiche RO: Treatment of infections associated with surgical implants. N Eng J Med 2004;350:1422-1429
8
Sohail MR, Uslan DZ, Khan AH, et al.: Management and outcome of permanent pacemaker and implantable
cardioverter-defibrillator infections. J Am Coll Cardiol 2007;49:1851-1859
9
Baddour LM, Epstein AE, Erickson CC, et al.: Update on cardiovascular implantable electronic device infections
and their management. A scientific statement from the American Heart Association. Circulation 2010;121:458-477
10
Cabell CH, Heidenreich PA, Chu VH, et al: Increasing rates of cardiac device infections among Medicare
beneficiaries:1990-1999. Am Heart J 2004;147:582-586
11
Voigt A, Shalaby A, Saba S: Continued rise in rates of cardiovascular implantable device infection in the United
States: Temporal trends and causative insights. Pacing Clin Electrophysiol 2010;33:414-419
12
McClellan MB, Tunis SR: Medicare coverage of ICDs. N Eng J Med 2005;352:222-224
13
Al-Khatib SM, Lucas Jollis JG, Malenka DJ, Wennberg DE: The relation between patients’ outcome and the
volume of cardioverter-defibrillator implantation procedures performed by physicians treating Medicare
beneficiaries. J Am Coll Cardiol 2005;46:1536-1540
14
Peterson PN, Daugherty SL, Wand Y, et al.: Gender differences in procedure-related adverse events in patients
receiving implantable cardioverter-defibrillator therapy. Circulation 2009;119:1078-1084
15
Curtis JP, Luebbert JJ, Wang Y, et al.: Association of physician certification and outcomes among patients
receiving an implantable cardioverter-defibrillator. JAMA 2009;301:1661-1670
16
Nery PB, Fernandes B, Nair GM, et al.: Device-related infection among patients with pacemakers and
implantable defibrillators: Incidence, risk factors, and consequences. J Cardiovasc Electrophysiol 2010;21:786-790
17
Uslan DZ, Sohail MR, St Sauver JL, et al.: Permanent pacemaker and implantable cardioverter-defibrillator
infection. A population-based study. Arch Int Med 2007;167:669-675
18
Ferguson TB Jr., Ferguson CL, Crites K, Crimmins-Reda P: The additional hospital costs generated in the
management of complications of pacemaker and defibrillator implantations. J Thorac Cardiovasc Surg
1996;111:742-75
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Borleffs CJM, Thijssen J, De Bie MK, et al.: Recurrent implantable cardioverter-defibrillator replacement is
associated with an increasing risk of pocket-related complications. Pacing Clin Electrophysiol 2010;33:1013-1019
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Poole JE, Gleva MJ, Mela T, et al. for the REPLACE Registry Investigators: Complication rates associated with
pacemaker or implantable cardioverter-defibrillator replacements and upgrade procedures: Results from the
REPLACE registry. Circulation 2010;122:1553-1561
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    • "Combined with an aging population, rapid and widespread acceptance of ICD indication has been suggested as a possible cause of the increase in the rate of CIED infections. This is because the size of the ICD generator is larger, and candidates for ICD therapy are more likely to have additional comorbidities [3]. In the PEOPLE study, a multicenter prospective survey investigating the incidence and risk factors of infectious complications in CIED procedures, several characteristics (fever 24 h before implantation, temporary pacing wires, and early intervention) were identified as risk factors for infection. "
    Full-text · Article · Jul 2016
    • "The number of implantable cardioverter defibrillators (ICD) and pacemakers (PM) has increased significantly during the past decades [1][2][3]as a result of the large amount of evidences supporting the positive effect on survival of cardiac devices especially of ICDs. The downside is represented by the psychological distress related to device implantation. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Device related distress negatively affects the quality of life of cardiac device recipients mostly of women. A submammary approach has been proposed to reduce the physical impact of the implantation. Our aim was to assess the safety of this approach and to evaluate the patients' acceptance of the device. Methods: We enrolled 42 patients who underwent a submammary device. The primary endpoint was the need for implant revision that was assessed in the study group compared with the overall control group of 72 standard cardiac device recipients (29 females and 43 males)and with the female group (29 females of controls). In the female population (42 women of the submammary group and 29 of controls) patients' acceptance was calculated with the Florida Patient Acceptance Survey (FPAS). Results: The rate of implant revision was similar in the two groups and the revision-free survival was comparable with a median follow-up of about six years (Log rank test p=0.949). Similar results were found when considering only the female population. Patients' acceptance was greater in the submammary group [total FPAS 85 (95%CI 83-86) vs 74.5 (95%CI 70.2-77.3) p<0,001] and a strongly significant superiority of the submammary group was found regarding body image concerns [10 (95%CI 10-10) vs 8 (95%CI 8-8) p<0.001) and device related distress [23 (95%CI 22-23) vs 1 (95%CI 1-1) p<0.001]. Conclusions: Submammary device implantation is safe and more accepted than standard approach. Our results should encourage cardiologists to suggest this approach to their patients for a better acceptance of the therapy.
    Full-text · Article · Jul 2016
    • "Hundreds of thousands of cardiac implantable electronic devices (CIEDs) are implanted worldwide annually [1, 2]. As indications have expanded and technology has improved, the incidence of device implantation has increased. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Guidelines advocate remote monitoring (RM) in patients with a cardiac implantable electronic device (CIED). However, it is not known when RM should be initiated. We hypothesized that prompt initiation of RM (within 91 days of implant) is associated with improved survival compared to delayed initiation. Methods: This retrospective, national, observational cohort study evaluated patients receiving new implants of market-released St. Jude Medical™ pacemakers (PM), implantable cardioverter defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices. Patients were assigned to one of two groups: an "RM Prompt" group, in which RM was initiated within 91 days of implant; and an "RM Delayed" group, in which RM was initiated >91 days but ≤365 days of implant. The primary endpoint was all-cause mortality. Results: The cohort included 106,027 patients followed for a mean of 2.6 ± 0.9 years. Overall, 47,014 (44 %) patients had a PM, 31,889 (30 %) patients had an ICD, 24,005 (23 %) patients had a CRT-D, and 3119 (3 %) patients had a CRT-P. Remote monitoring was initiated promptly (median 4 weeks [IQR 2, 8 weeks]) in 66,070 (62 %) patients; in the other 39,957 (38 %) patients, RM initiation was delayed (median 24 weeks [IQR 18, 34 weeks]). In comparison to delayed initiation, prompt initiation of RM was associated with a lower mortality rate (4023 vs. 4679 per 100,000 patient-years, p < 0.001) and greater adjusted survival (HR 1.18 [95 % CI 1.13-1.22], p < 0.001). Conclusions: Our data, for the first time, show improved survival in patients enrolled promptly into RM following CIED implantation. This advantage was observed across all CIED device types.
    Full-text · Article · Feb 2016
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