History
An 86-year-old gentleman was seen in the clinic for concerns regarding drainage at the site of his cardiac device on the left chest wall. His history was significant for ischemic heart disease and sinus node dysfunction, for which he had undergone pacemaker placement 2 years previously. At that time, his ejection fraction was estimated to be 38%. More recently, he was found to have New York Heart Association class III symptoms of congestive heart failure despite aggressive medical management. His ejection fraction was found to be 30%, and therefore his device was upgraded to a cardiac resynchronization therapy defibrillator (CRT-D) 6 weeks before presentation. At the time of this procedure, the old right ventricular pacing lead was removed but the chronic atrial lead was left in place. A routine recheck revealed the patient’s P wave to be significantly reduced, at 0.2 mV. Device interrogation confirmed that there was no capture on the atrial lead, and therefore he underwent atrial lead revision 3 weeks before presentation. This procedure was complicated by a postoperative hematoma at the surgical site that was managed conservatively. A few days after the procedure, he noticed pain, redness, and drainage from the device pocket in the left chest wall (Figure 35-1) and sought further evaluation at the clinic.
The review of systems in this patient was negative for fever or chills. He did have some fatigue and worsening shortness of breath but did not report chest pain or sputum production.
His other relevant comorbidities included prostate and laryngeal cancer, hypertension, hyperlipidemia, and iron deficiency anemia without an obvious source of bleeding. He had undergone a coronary artery bypass graft in 1994.
Current Medications
The patient was taking clopidogrel 75 mg daily, ferrous sulfate 325 mg (65 mg iron) daily, ramipril 5 mg daily, metoprolol 25 mg daily, isosorbide mononitrate 30 mg daily, furosemide 20 mg daily, niacin 1000 mg daily, simvastatin 40 mg daily, and aspirin 81 mg daily.
Current Symptoms
The patient was experiencing erythema, pain, and drainage at the site of device pocket in the left chest wall.
Physical Examination
Comments
Clinical examination shows dehiscence of surgical incision with purulent drainage and surrounding erythema consistent with cardiac device infection. The examination is also concerning for decompensated heart failure, as evidenced by increased jugular vein distention and peripheral edema.
FIGURE 35-1 Pain, redness, and drainage from the device pocket in the left chest wall.
Laboratory Data
Comments
Routine laboratory tests, including hemoglobin, leukocyte count, platelets, electrolytes, and inflammatory markers such as erythrocye sedimentation rate (ESR) and C-reactive protein (CRP) are neither sensitive nor specific for the diagnosis of cardiac device–related infection. The patient does have anemia and leukocytosis. These findings are not unexpected given the clinical history, which in itself is diagnostic of cardiac device infection.
Electrocardiogram
Findings
Normal sinus rhythm with biventricular pacing.
Comments
Electrocardiogram can provide clues to intracardiac complications of device-related infections such as conduction defects or heart block that may arise secondary to abscess formation.
Chest Radiograph
Findings
The chest radiograft revealed a small left pleural effusion with increased pulmonary vascularity and mildly increased perihilar prominence. Lungs were otherwise clear. Sternotomy wires and a left pectoral biventricular implanted cardiac device was seen.
Comments
Chest radiography can sometimes be helpful to detect septic emboli that arise as a result of dislodgement of lead vegetations. Our patient did not have these findings on his chest radiograph. Evidence of decompensated heart failure was present.
Echocardiogram
Findings
Echocardiogram revealed mild left ventricular enlargement with moderate to severely reduced systolic function. The calculated left ventricular ejection fraction was 30%. Moderate to severe generalized left ventricular hypokinesis also was present. Mild right ventricular enlargement was noted, with moderately reduced systolic function. The estimated right ventricular systolic pressure was 50 mm Hg (systolic blood pressure was 131 mm Hg). Calcific aortic valve stenosis (low output, low gradient) with a gradient of 26 mm Hg and calculated valve area of 0.92 cm2 was noted.
Comments
The transthoracic echocardiogram did not reveal presence of vegetations. However, because of contiguity between the generator and leads, the patient is at significant risk for developing a more invasive infection if prompt treatment is not initiated. A transesophageal echocardiogram is more sensitive for visualization of valvular or lead vegetations and should be pursued in cases in which a blood culture is reported to be positive.
Focused Clinical Questions and Discussion Points
Question
Based on the available epidemiologic data, what is the most likely pathogen responsible for this infection?
Discussion
The majority of cardiovascular implantable elctronic device (CIED) infections are caused by coagulase-negative staphylococci and Staphylococcus aureus. According to an earlier report from our institution, approximately 42% of infections were caused by coagulase-negative staphylococci and 29% of infections were caused by S. aureus. Considering that a large proportion of these organisms are resistant to oxacillin, vancomycin typically is used as empiric treatment until susceptibility data are available to guide specific antimicrobial therapy. Other less common organisms implicated as causative agents for CIED infection include other gram-positive cocci (4%), gram-negative cocci (9%), polymicrobial sources (7%), and fungal organisms (2%).7 Occasionally, the etiologic microorganism cannot be identified, usually because of previous antimicrobial therapy. Therefore every attempt should be made to establish a microbiologic diagnosis before starting empiric antibiotic therapy. Culture-negative cases are often treated with broad-spectrum antibiotics, which places the patient at risk for greater adverse events, including but not limited to renal and hepatic dysfunction, superinfection, and cytopenia. Additionally, increased use of broad-spectrum antibiotics may contribute to the emergence of resistance.
For this patient, swabs of the serous drainage were collected and grew coagulase-negative Staphylococcus after 24 hours of incubation.
Question
What is the prevalence of CRT-D infections, and what factors increased the risk for infection?
Discussion
Overall, the rate of CIED infections seems to be rising disproportionately in contrast to the rate of device implantation, despite improvements in surgical techniques such as placement of transvenous leads instead of epicardial electrode patches, more operator experience with a larger volume of implantations, and use of prophylactic antibiotics. This increasing rate of infections has been attributed, in part, to implantation of CIEDs in sicker patients with more comorbidities and more complex procedures.10 According to a recent study,5 prevalence of CRT device infection was found to be 4.3% at 2.6 years of follow-up. The annual incidence was calculated to be 1.7% per year.5 These numbers appear to be higher in contrast to rates of defibrillator or pacemaker infections, which have been reported at 1.2% at a similar time interval in a retrospective study3 and 1.9 per 1000 device-years in a population-based study.9 However, the infection rates in the REPLACE registry were reported to be low at 1.3%, similar to the overall incidence of device-related infections, although the follow-up was limited to 6 months and the study was not limited to only CRT devices. It was also observed that the centers that reported more than 5% infection rates used topical antisepsis with povidine-iodine, had lower rates of device implantation, or treated patients with an increased number of comorbidities.8
Some studies have evaluated risk factors for CIED infections. However, specific data regarding CRT device infections are limited. In one of the studies previously noted,5 hemodialysis, increased implantation procedure time, device revision, and CRT-D placement were found to be independent risk factors for device infection on multivariate analysis. Other factors such as placement of epicardial leads and complications at the surgical site, such as hematoma formation, also have been reported to increase the risk for device infection.6
Question
What are the clinical manifestations of a cardiac device infection?
Discussion
Clinical presentation of cardiac device infection is variable and depends on timing of onset of infection, causative pathogen, and area of device involvement. The most common manifestation of a cardiac device infection in the early postoperative period includes pain, swelling, redness, and discharge at the surgical site (device generator pocket). Systemic manifestations of infection such as fever, chills, sweating, anorexia, or decompensated heart failure may be absent because of the localized nature of the infection. These systemic manifestations are more prevalent in cases in which the device becomes infected secondary to hematogeneous seeding from a distant source of bloodstream infection, especially with S. aureus. Occasionally, patients may present with device or lead erosion without gross inflammatory changes.7 In these circumstances, the device is assumed to be infected because of contamination from the skin flora. Finally, lead endocarditis may present with either constitutional symptoms or embolic complications such as septic emboli to the lungs.
Question
What diagnostic tests are indicated to confirm CRT infection in this case?
Discussion
Diagnosis of CRT device infection usually is a clinical one. Routine laboratory tests such as leukocyte count, platelet count, ESR, and CRP are frequently obtained but can be normal in cases with localized infection. Blood cultures should be obtained in all cases of suspected CRT device infection, not only to define the extent of infection but also to help establish microbiologic cause and determine the type and duration of antibiotic therapy. A positive blood culture in a patient with suspected infected device should prompt evaluation with a transesophageal echocardiogram to look for vegetations on the device leads or heart valves or complications such as myocardial abscess. Persistently positive blood cultures, in the absence of any other focus of infection, in a patient with a cardiac device suggest device-related endocarditis even in the absence of any echocardiographic evidence of gross vegetation.2
All attempts should be made to reach a specific microbiologic diagnosis by obtaining swabs from the generator pocket or device surface for bacterial cultures at the time of explantation. Moreover, pocket tissue and lead tip cultures should be performed to help establish the microbiologic diagnosis. However, positive lead tip cultures should not always be interpreted as evidence of lead endocarditis because lead tips can be contaminated while being pulled percutaneously through an infected device pocket.
The patient described in this case underwent transesophageal echocardiography that did not reveal any vegetations or intracardiac complications such as myocardial abscess formation. Blood cultures were drawn and remained negative after 5 days of incubation.
Question
What would be considered the optimal management of the infected device in this case?
Discussion
Multiple published studies related to cardiac device infections suggest that optimal management of an infected cardiac device includes both the administration of appropriate systemic antibiotics and complete removal of the device, including intracardiac leads. In a large, single-center, retrospective study, conservative treatment with just antibiotics and without device removal was associated with a sevenfold increase in 30-day mortality. Additionally, prompt hardware removal was associated with a threefold decrease in 1-year mortality in contrast to delayed device removal, allowing for initial conservative management with antibiotics alone.2 These data are consistent with findings from a subsequent study in which relapse rates were observed to be significantly lower with device removal in contrast to hardware retention (2.6% vs. 61.4%).4
In contemporary practice, leads are extracted in the majority of cases by percutaneous approach at specialized centers. More invasive procedures, such as sternotomy, are reserved for cases in which the percutaneous procedure cannot be successfully performed or to manage any unintended complication of the percutaneous extraction procedure such as bleeding or vascular perforation. However, the rates of complications associated with percutanous lead removal are very low—less than 1% in experienced medical centers. Treatment algorithms and guidelines have been published by the American Heart Association and support a combined medical and surgical approach involving administration of intravenous antibiotics and complete removal of the infected device, including the generator and all leads, regardless of clinical presentation.1 Oxacillin, nafcillin, or cefazolin typically is used for treatment of susceptible strains of staphylococci. However, because of high rates of oxacillin resistance seen in species of staphylococci, vancomycin typically is used for empiric treatment until susceptibility data become available. The duration of antibiotic therapy depends on the type of infection. In cases in which infection is limited to the pocket site, 7 to 10 days of antibiotic therapy after device extraction is adequate in most cases. However, cases of device infection associated with bloodstream infection are typically treated with a 14-day course of intravenous antibiotics after device removal. Patients with associated complications in the form of valvular endocarditis, septic thrombophlebitis, or osteomyelitis require a longer course of intravenous antibiotics lasting 28 to 42 days, depending on the particular complication and causative pathogen.
All patients should be assessed for the need for ongoing device therapy before implantation of a new device. Reimplantation, if required, should be done on the contralateral side once the blood culture results are available and pocket infection is under control.
The patient in this case underwent complete percutaneous removal of the device (including generator and leads). He developed transient hypotension during the procedure that responded to intravenous fluid bolus. He was subsequently started on vancomycin intravenously. The susceptibility results revealed the organism to be oxacillin resistant, and he was therefore continued on intravenous vancomycin, which he received for a total of 14 days after device extraction. He underwent replacement of the CRT-D device on the contralateral chest wall 2 days after removal of the infected device. His latest evaluation was performed 2 months after device replacement, and he was found to be symptom free without evidence of relapse or recurrence of the infection.
Final Diagnosis
The final diagnosis in this patient was CRT device pocket infection with coagulase-negative Staphylococcus.
Plan of Action
The plan for this patient was combined medical and surgical management.
Intervention
Percutaneous generator and lead extraction was performed in this patient.
Outcome
The outcome was complete cure of the infection.
Selected References
1. Baddour L.M., Epstein A.E., Erickson C.C. 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.
2. Le K.Y., Sohail M.R., Friedman P.A. et al. Impact of timing of device removal on mortality in patients with cardiovascular implantable electronic device infections. Heart Rhythm. 2011;8:1678–1685.
3. Mela T., McGovern B.A., Garan H. et al. Long-term infection rates associated with the pectoral versus abdominal approach to cardioverter-defibrillator implants. Am J Cardiol. 2001;88:750–753.
4. Pichlmaier M., Knigina L., Kutschka I. et al. Complete removal as a routine treatment for any cardiovascular implantable electronic device-associated infection. J Thorac Cardiovasc Surg. 2011;142:1482–1490.
5. Romeyer-Bouchard C., Da Costa A., Dauphinot V. et al. Prevalence and risk factors related to infections of cardiac resynchronization therapy devices. Eur Heart J. 2010;31:203–210.
6. Sohail M.R., Hussain S., Le K.Y. et al. Risk factors associated with early- versus late-onset implantable cardioverter-defibrillator infections. J Interv Card Electrophysiol. 2011;31:171–183.
7. Sohail M.R., Uslan D.Z., Khan A.H. et al. Management and outcome of permanent pacemaker and implantable cardioverter-defibrillator infections. J Am Coll Cardiol. 2007;49:1851–1859.
8. Uslan D.Z., Gleva M.J., Warren D.K. et al. Cardiovascular implantable electronic device replacement infections and prevention: results from the REPLACE Registry. Pacing Clin Electrophysiol. 2012;35:81–87.
9. Uslan D.Z., Sohail M.R., St Sauver J.L. et al. Permanent pacemaker and implantable cardioverter defibrillator infection: a population-based study. Arch Intern Med. 2007;167:669–675.
10. Voigt A., Shalaby A., Saba S. Continued rise in rates of cardiovascular implantable electronic device infections in the United States: temporal trends and causative insights. Pacing Clin Electrophysiol. 2010;33:414–419.
