- Email: [email protected]
Cardiac implantable electronic device infections: From recognizing risk to prevention
Accepted Manuscript Cardiac Implantable Electronic Device Infections: From Recognizing Risk to Prevention William F. McIntyre, Jeff S. Healey PII:
S1547-5271(17)30349-1
DOI:
10.1016/j.hrthm.2017.03.027
Reference:
HRTHM 7088
To appear in:
Heart Rhythm
Received Date: 15 March 2017
Please cite this article as: McIntyre WF, Healey JS, Cardiac Implantable Electronic Device Infections: From Recognizing Risk to Prevention, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.03.027. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
Cardiac Implantable Electronic Device Infections: From Recognizing Risk to Prevention
RI PT
William F McIntyre, Jeff S Healey
SC
McMaster University, Hamilton, Ontario, Canada Population Health Research Institute, Hamilton, Ontario, Canada
M AN U
Word count: 1204
TE D
Address for Correspondence Dr Jeff S Healey David Braley Cardiovascular and Stroke Research Institute Population Health Research Institute McMaster University Hamilton, ON, L8L 2X2, Canada [email protected]
AC C
EP
Conflicts of Interest: WFM: None JSH: Dr. Healey has received research grants Boston Scientific, Medtronic, and St. Jude Medical, and speaking fees from Boston Scientific
1
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
More than a million cardiac implantable electronic devices (CIED), including permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD) and cardiac
RI PT
resynchronization therapy devices (CRT) are implanted worldwide every year and their use is growing 1. Device related infection (DRI) is one of the most common, and
significant complications associated with CIEDs, and its incidence is increasing 2. This
SC
iatrogenic disease has a significant impact on morbidity, mortality, and healthcare costs. Understanding risk factors for DRI and testing and implementing strategies to reduce its
M AN U
incidence are of paramount importance.
In this issue of Heart Rhythm, Joy and colleagues report on the incidence and predictors of DRI in a cohort of patients derived from the U.S. National Inpatient Sample (NIS) database 3. In their sample of over 4 million device-related procedures performed
TE D
between 2000-2012, the incidence of DRI, identified using and ICD-9-CM codes for CIED removal and device-related systemic infection, was 2.06%. Of particular concern, the incidence of DRI increased over the study period from 1.45% of all procedures to
EP
3.41% (p<0.001). These estimates are in line with those that have been reported from
AC C
other sources and highlight a trend towards increased rates of DRI 4, 5. It is important to understand the reasons the observed increase in the frequency of DRI; whether this reflects a simple increase in the volume of CIED procedures, the consequence of conducting more complex procedures in patients with more comorbidities or other factors. Joy and colleagues noted that the US witnessed more than a doubling in the incidence of DRI over their study period, which was out-of-proportion to the increase in the number of CIED implant procedures 3. However, they demonstrated an increase in
2
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
the prevalence of co-morbidities known to be associated with an increased risk of DRT; including diabetes mellitus, congestive heart failure, chronic kidney disease and respiratory disease 2. Furthermore, they observed an increase in the number of CRT
RI PT
implants and CIED replacement procedures; both shown to be associated with a higher
risk of DRI than de-novo implantation of single or dual-chamber devices 1, 4, 6, 7. Thus, the current study provides some insights into the reasons for the increase in DRI, and helps
SC
guide efforts to prevent DRI.
M AN U
Given the frequency and consequences of DRI, it is important to determine what can be done to decrease the rate of DRI. In their study, Joy and colleagues identify CRT, diabetes mellitus, hematoma, malnutrition, venous thromboembolism, chronic kidney disease and organ transplantation as risk factors for DRI3. Although most of these factors are not modifiable, refinement of implant technique, such as CIED implantation with
TE D
continuation of warfarin, has been shown to reduce the risk of hematoma and that this in turn is associated with a lower risk of infection8. Unfortunately, the NIS database does not contain information regarding other important and potentially modifiable peri-
EP
procedural characteristics such as the type of skin preparation and the use of prophylactic
AC C
antibiotics. A recent systematic review and meta-analysis found that post-operative hematoma, re-intervention for lead dislodgement, device replacement/revision, lack of antibiotic prophylaxis, temporary pacing, inexperienced operators, and procedure duration were all significant predictors of DRI9. Joy and colleagues call for the creation of a prospective, comprehensive registry to accurately track outcomes of CIEDs3. Such a registry would be expensive and take several years to accrue sufficient data, but could provide vital insights to curb the rising rate of DRI.
3
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
As we continue to try to understand the factors responsible for the increasing rate of DRI, we await the results of two large randomized clinical trials, which are assessing interventions to decrease the risk DRI. The Prevention of Arrhythmia Device Infection
RI PT
Trial (PADIT, NCT01628666) has completed recruitment and follow-up is ongoing10. This large, randomized, cluster-crossover trial is comparing a center-wide policy of
incremental intravenous, intra-cavitary and post-operative oral antibiotic therapy against
SC
conventional, single-dose, antibiotic prophylaxis in high-risk patients undergoing
arrhythmia device procedures. The World-wide Randomized Antibiotic Envelope
M AN U
Infection Prevention Trial (WRAP-IT, NCT02277990) clinical trial is currently enrolling patients 11, who are randomized to determine if the use of an absorbable antibacterial envelope reduces major CIED infections following CIED generator replacement, revision, or de novo CRT-D implant. Recognizing patients who are at highest risk for
AC C
EP
iatrogenic disease.
TE D
DRI and applying evidence-based strategies will be key in reducing the burden of this
4
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
AC C
EP
TE D
M AN U
SC
RI PT
References 1. Mond HG and Proclemer A. The 11th world survey of cardiac pacing and implantable cardioverter-defibrillators: calendar year 2009--a World Society of Arrhythmia's project. Pacing Clin Electrophysiol. 2011;34:1013-27. 2. Greenspon AJ, Patel JD, Lau E, Ochoa JA, Frisch DR, Ho RT, Pavri BB and Kurtz SM. 16-year trends in the infection burden for pacemakers and implantable cardioverter-defibrillators in the United States 1993 to 2008. J Am Coll Cardiol. 2011;58:1001-6. 3. Joy S and al e. Cardiac Implantable Electronic Device Infections: Who is at Greatest Risk? Heart Rhythm. 2017. 4. Poole JE, Gleva MJ, Mela T, Chung MK, Uslan DZ, Borge R, Gottipaty V, Shinn T, Dan D, Feldman LA, Seide H, Winston SA, Gallagher JJ, Langberg JJ, Mitchell K, Holcomb R and Investigators ftRR. Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and Upgrade Procedures: Results From the REPLACE Registry. Circulation. 2010;122:1553-1561. 5. Kirkfeldt RE, Johansen JB, Nohr EA, Jorgensen OD and Nielsen JC. Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark. Eur Heart J. 2014;35:1186-94. 6. Jan Willem Borleffs C, Thijssen J, De Bie MK, Van Rees JB, Van Welsenes GH, Van Erven L, Bax JJ, Cannegieter SC and Schalij MJ. Recurrent Implantable Cardioverter-Defibrillator Replacement Is Associated with an Increasing Risk of PocketRelated Complications. Pacing and Clinical Electrophysiology. 2010;33:1013-1019. 7. Landolina M, Gasparini M, Lunati M, Iacopino S, Boriani G, Bonanno C, Vado A, Proclemer A, Capucci A, Zucchiatti C, Valsecchi S, Ricci RP, Santini M and Cardiovascular Centers Participating in the ClinicalService P. Long-term complications related to biventricular defibrillator implantation: rate of surgical revisions and impact on survival: insights from the Italian Clinical Service Database. Circulation. 2011;123:252635. 8. Essebag V VA, Healey JS, Krahn AD, Kalfon E, Coutu B, Ayala-Paredes F, Tang ASL, Sapp JL, Sturmer M, Keren A, Wells GA, Birnie DH. Clinically significant pocket hematoma increases the long-term risk of device infection: BRUISE CONTROL Infection Study. J Am Coll Cardiolo. 67:1300-1308. 9. Polyzos KA, Konstantelias AA and Falagas ME. Risk factors for cardiac implantable electronic device infection: a systematic review and meta-analysis. Europace. 2015;17:767-77. 10. Connolly SJ, Philippon F, Longtin Y, Casanova A, Birnie DH, Exner DV, Dorian P, Prakash R, Alings M and Krahn AD. Randomized cluster crossover trials for reliable, efficient, comparative effectiveness testing: design of the Prevention of Arrhythmia Device Infection Trial (PADIT). Can J Cardiol. 2013;29:652-8. 11. Tarakji KG, Mittal S, Kennergren C, Corey R, Poole J, Stromberg K, Lexcen DR and Wilkoff BL. Worldwide Randomized Antibiotic EnveloPe Infection PrevenTion Trial (WRAP-IT). Am Heart J. 2016;180:12-21.
5
S1547-5271(17)30349-1
DOI:
10.1016/j.hrthm.2017.03.027
Reference:
HRTHM 7088
To appear in:
Heart Rhythm
Received Date: 15 March 2017
Please cite this article as: McIntyre WF, Healey JS, Cardiac Implantable Electronic Device Infections: From Recognizing Risk to Prevention, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.03.027. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
Cardiac Implantable Electronic Device Infections: From Recognizing Risk to Prevention
RI PT
William F McIntyre, Jeff S Healey
SC
McMaster University, Hamilton, Ontario, Canada Population Health Research Institute, Hamilton, Ontario, Canada
M AN U
Word count: 1204
TE D
Address for Correspondence Dr Jeff S Healey David Braley Cardiovascular and Stroke Research Institute Population Health Research Institute McMaster University Hamilton, ON, L8L 2X2, Canada [email protected]
AC C
EP
Conflicts of Interest: WFM: None JSH: Dr. Healey has received research grants Boston Scientific, Medtronic, and St. Jude Medical, and speaking fees from Boston Scientific
1
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
More than a million cardiac implantable electronic devices (CIED), including permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD) and cardiac
RI PT
resynchronization therapy devices (CRT) are implanted worldwide every year and their use is growing 1. Device related infection (DRI) is one of the most common, and
significant complications associated with CIEDs, and its incidence is increasing 2. This
SC
iatrogenic disease has a significant impact on morbidity, mortality, and healthcare costs. Understanding risk factors for DRI and testing and implementing strategies to reduce its
M AN U
incidence are of paramount importance.
In this issue of Heart Rhythm, Joy and colleagues report on the incidence and predictors of DRI in a cohort of patients derived from the U.S. National Inpatient Sample (NIS) database 3. In their sample of over 4 million device-related procedures performed
TE D
between 2000-2012, the incidence of DRI, identified using and ICD-9-CM codes for CIED removal and device-related systemic infection, was 2.06%. Of particular concern, the incidence of DRI increased over the study period from 1.45% of all procedures to
EP
3.41% (p<0.001). These estimates are in line with those that have been reported from
AC C
other sources and highlight a trend towards increased rates of DRI 4, 5. It is important to understand the reasons the observed increase in the frequency of DRI; whether this reflects a simple increase in the volume of CIED procedures, the consequence of conducting more complex procedures in patients with more comorbidities or other factors. Joy and colleagues noted that the US witnessed more than a doubling in the incidence of DRI over their study period, which was out-of-proportion to the increase in the number of CIED implant procedures 3. However, they demonstrated an increase in
2
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
the prevalence of co-morbidities known to be associated with an increased risk of DRT; including diabetes mellitus, congestive heart failure, chronic kidney disease and respiratory disease 2. Furthermore, they observed an increase in the number of CRT
RI PT
implants and CIED replacement procedures; both shown to be associated with a higher
risk of DRI than de-novo implantation of single or dual-chamber devices 1, 4, 6, 7. Thus, the current study provides some insights into the reasons for the increase in DRI, and helps
SC
guide efforts to prevent DRI.
M AN U
Given the frequency and consequences of DRI, it is important to determine what can be done to decrease the rate of DRI. In their study, Joy and colleagues identify CRT, diabetes mellitus, hematoma, malnutrition, venous thromboembolism, chronic kidney disease and organ transplantation as risk factors for DRI3. Although most of these factors are not modifiable, refinement of implant technique, such as CIED implantation with
TE D
continuation of warfarin, has been shown to reduce the risk of hematoma and that this in turn is associated with a lower risk of infection8. Unfortunately, the NIS database does not contain information regarding other important and potentially modifiable peri-
EP
procedural characteristics such as the type of skin preparation and the use of prophylactic
AC C
antibiotics. A recent systematic review and meta-analysis found that post-operative hematoma, re-intervention for lead dislodgement, device replacement/revision, lack of antibiotic prophylaxis, temporary pacing, inexperienced operators, and procedure duration were all significant predictors of DRI9. Joy and colleagues call for the creation of a prospective, comprehensive registry to accurately track outcomes of CIEDs3. Such a registry would be expensive and take several years to accrue sufficient data, but could provide vital insights to curb the rising rate of DRI.
3
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
As we continue to try to understand the factors responsible for the increasing rate of DRI, we await the results of two large randomized clinical trials, which are assessing interventions to decrease the risk DRI. The Prevention of Arrhythmia Device Infection
RI PT
Trial (PADIT, NCT01628666) has completed recruitment and follow-up is ongoing10. This large, randomized, cluster-crossover trial is comparing a center-wide policy of
incremental intravenous, intra-cavitary and post-operative oral antibiotic therapy against
SC
conventional, single-dose, antibiotic prophylaxis in high-risk patients undergoing
arrhythmia device procedures. The World-wide Randomized Antibiotic Envelope
M AN U
Infection Prevention Trial (WRAP-IT, NCT02277990) clinical trial is currently enrolling patients 11, who are randomized to determine if the use of an absorbable antibacterial envelope reduces major CIED infections following CIED generator replacement, revision, or de novo CRT-D implant. Recognizing patients who are at highest risk for
AC C
EP
iatrogenic disease.
TE D
DRI and applying evidence-based strategies will be key in reducing the burden of this
4
ACCEPTED MANUSCRIPT HRS Editorial
McIntyre WF and Healey JS
AC C
EP
TE D
M AN U
SC
RI PT
References 1. Mond HG and Proclemer A. The 11th world survey of cardiac pacing and implantable cardioverter-defibrillators: calendar year 2009--a World Society of Arrhythmia's project. Pacing Clin Electrophysiol. 2011;34:1013-27. 2. Greenspon AJ, Patel JD, Lau E, Ochoa JA, Frisch DR, Ho RT, Pavri BB and Kurtz SM. 16-year trends in the infection burden for pacemakers and implantable cardioverter-defibrillators in the United States 1993 to 2008. J Am Coll Cardiol. 2011;58:1001-6. 3. Joy S and al e. Cardiac Implantable Electronic Device Infections: Who is at Greatest Risk? Heart Rhythm. 2017. 4. Poole JE, Gleva MJ, Mela T, Chung MK, Uslan DZ, Borge R, Gottipaty V, Shinn T, Dan D, Feldman LA, Seide H, Winston SA, Gallagher JJ, Langberg JJ, Mitchell K, Holcomb R and Investigators ftRR. Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and Upgrade Procedures: Results From the REPLACE Registry. Circulation. 2010;122:1553-1561. 5. Kirkfeldt RE, Johansen JB, Nohr EA, Jorgensen OD and Nielsen JC. Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark. Eur Heart J. 2014;35:1186-94. 6. Jan Willem Borleffs C, Thijssen J, De Bie MK, Van Rees JB, Van Welsenes GH, Van Erven L, Bax JJ, Cannegieter SC and Schalij MJ. Recurrent Implantable Cardioverter-Defibrillator Replacement Is Associated with an Increasing Risk of PocketRelated Complications. Pacing and Clinical Electrophysiology. 2010;33:1013-1019. 7. Landolina M, Gasparini M, Lunati M, Iacopino S, Boriani G, Bonanno C, Vado A, Proclemer A, Capucci A, Zucchiatti C, Valsecchi S, Ricci RP, Santini M and Cardiovascular Centers Participating in the ClinicalService P. Long-term complications related to biventricular defibrillator implantation: rate of surgical revisions and impact on survival: insights from the Italian Clinical Service Database. Circulation. 2011;123:252635. 8. Essebag V VA, Healey JS, Krahn AD, Kalfon E, Coutu B, Ayala-Paredes F, Tang ASL, Sapp JL, Sturmer M, Keren A, Wells GA, Birnie DH. Clinically significant pocket hematoma increases the long-term risk of device infection: BRUISE CONTROL Infection Study. J Am Coll Cardiolo. 67:1300-1308. 9. Polyzos KA, Konstantelias AA and Falagas ME. Risk factors for cardiac implantable electronic device infection: a systematic review and meta-analysis. Europace. 2015;17:767-77. 10. Connolly SJ, Philippon F, Longtin Y, Casanova A, Birnie DH, Exner DV, Dorian P, Prakash R, Alings M and Krahn AD. Randomized cluster crossover trials for reliable, efficient, comparative effectiveness testing: design of the Prevention of Arrhythmia Device Infection Trial (PADIT). Can J Cardiol. 2013;29:652-8. 11. Tarakji KG, Mittal S, Kennergren C, Corey R, Poole J, Stromberg K, Lexcen DR and Wilkoff BL. Worldwide Randomized Antibiotic EnveloPe Infection PrevenTion Trial (WRAP-IT). Am Heart J. 2016;180:12-21.
5