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Ann Thorac Surg 2006;82:524-529
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Surgical Management of Infective Endocarditis: Early Predictors of Short-Term Morbidity and Mortality

Davinder S. Jassal, MDa,*, Tomas G. Neilan, MDa, Aruna D. Pradhan, MDa, Karen E. Lynch, RNb, Gus Vlahakes, MDb, Arvind K. Agnihotri, MDb, Michael H. Picard, MDa

a Cardiac Ultrasound Laboratory, Cardiology Division, Department of Medicine, Boston, Massachusetts
b Cardiac Surgery Division, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Accepted for publication February 6, 2006.

* Address correspondence to Dr Jassal, Department of Cardiology, Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Harvard Medical School, VBK-508, 55 Fruit Street, Boston, MA 02114 (Email: djassal{at}partners.org).


Adult cardiac surgery: The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

 

   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
BACKGROUND: Infective endocarditis is a diagnostic and therapeutic challenge that ultimately requires surgical intervention in 20% of all cases. Early determinants of morbidity and mortality in this high risk population are not well described.

METHODS: The aim of this study was to determine preoperative clinical, microbiological, electrocardiographic, and echocardiographic variables that predicted the need for permanent pacemaker implantation and in-hospital death in a surgical cohort of patients with active infective endocarditis.

RESULTS: We identified 91 patients (61 males and 30 females, mean age 58 ± 16 years) who underwent surgical intervention for active culture-positive infective endocarditis as defined by the Duke criteria. Native valve infective endocarditis was present in 78 (85.7%) and prosthetic valve endocarditis in 13 (14.3%) of cases. The aortic valve was infected in 61 (67.0%), the mitral in 35 (38.5%), and multiple valves in 8 patients (8.8%). The most common indication for surgical intervention was intractable heart failure. Twenty-two patients (24.2%) required pacemakers, while there were 14 (15.4%) in-hospital deaths. In age-adjusted and gender-adjusted analyses, the presence of left bundle branch block on preoperative electrocardiogram (ECG) and presence of depressed left ventricular systolic function (ejection fraction [EF] < 50%) predicted the need for a permanent pacemaker implantation, while the presence of depressed left ventricular function predicted in-hospital mortality.

CONCLUSIONS: Preoperative ECG findings of left bundle branch block and reduced left ventricular function may allow for early risk stratification of this high risk population.

Acute infective endocarditis (IE) is a clinical challenge that is often associated with high patient morbidity and mortality [1]. Despite appropriate antibiotic use, surgical intervention is required in 20% of cases [2]. Among patients who undergo surgical intervention, 10% require permanent pacemaker implantation [2].

The indications for surgery in IE have continued to evolve, but frequently include intractable heart failure, abscess formation, recurrent embolic events, organism involved, and presence of prosthetic material [3–8]. While mortality has improved from 30% to 15% over the past two decades, it remains substantial [1].

With increasing demands for surgery in patients with IE the identification of preoperative variables that may identify the highest risk patients in this surgical cohort would be clinically useful. Although prior studies have evaluated clinical, microbiological, and echocardiographic (Echo) predictors of short-term outcomes in patients with acute IE [9–13], little is known about early determinants of outcomes in the current era among high-risk surgically treated cohorts [14–18] and we have found no studies that have examined factors associated with the need for pacemaker implantation.

We thus sought to evaluate the impact of preoperative clinical variables including the Duke criteria for IE, preoperative ECG, and echocardiographic findings on short-term morbidity and mortality in patients surgically managed for endocarditis.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
From 1995 to 2004 inclusive, 637 patients were identified with acute infective IE at the Massachusetts General Hospital. Of this population, 91 consecutive patients having undergone valve replacement for acute culture-positive IE were identified from a computer registry database of cardiac surgical patients. The database captured detailed information on a wide range of preoperative, intraoperative, and postoperative variables for all patients undergoing cardiac surgery at this tertiary care center. The study protocol was approved by the local institutional review board on Aug 16, 2004 and individual patient consent was waived.

In addition to data that was available through the database, the medical records of all 91 patients were extensively reviewed. Preoperative clinical variables of interest included age, gender, diabetes, Duke criteria for infective endocarditis, infecting microorganism, and indication for surgery. Intraoperative variables of interest included the number and type of valves infected, intraoperative pathological findings, and surgical procedure performed. Postoperative variables that were considered included need for transfusion (>2 units of packed red blood cells), prolonged ventilation greater than 24 hours, cerebrovascular accident, need for dialysis, permanent pacemaker implantation, rate of reoperation, and in-hospital mortality. Need for postoperative permanent pacemaker implantation and in-hospital death were the short-term clinical outcomes of interest.

Preoperative ECG and echocardiography were evaluated in all 91 patients. Conduction abnormalities including first-degree block, interventricular conduction delay (defined as QRS >120 msec), right bundle branch block (RBBB), and left bundle branch block (LBBB) were recorded. Right bundle branch block was defined as: (1) QRS >120 msec; (2) rsR' pattern in lead V1 or V2; and (3) S wave longer than duration of the R wave in leads V6 and I. Left bundle branch block was defined as: (1) QRS >120 msec; (2) broad and notched R waves in leads V5, V6, and aVL; (3) absent Q wave in left-sided leads; and (4) R wave > 60 msec in leads V5 and V6. During the study period, all 91 patients had a preoperative transthoracic echocardiogram (TTE), 80 patients had a preoperative transesophageal echocardiogram (TEE), and 85 patients had an intraoperative TEE. Echocardiographic parameters of interest included the presence of vegetation, maximum length of vegetation, abscess, fistula formation, infected valve, left atrial dimension (anterior-posterior measurement in the parasternal long axis), left ventricular cavity dimensions, and ejection fraction (EF). An EF of > 0.50 was defined as normal.

The data are summarized as mean ± SD or number (percentage). Univariable analyses were conducted using the t test for comparison of means between groups and the Fisher exact test for comparison of categoric parameters. Multivariable models were constructed using stepwise logistic regression with an entry probability criterion of 0.20 and stay criterion of 0.10, in order to identify preoperative characteristics that were independently associated with the two endpoints of postoperative permanent pacemaker implantation and in-hospital death. Age and gender were forced into both statistical models. Kaplan-Meier survival curves were constructed for postoperative survival by category of left ventricular (LV) dysfunction. The log-rank test was used to assess differences in postoperative survival. The Statistical Analysis System (SAS Institute, Cary, NC) 8.01 was used to perform the analysis.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
There were 61 men and 30 women averaging 58 ± 16 years of age with a diagnosis of culture positive active IE as defined by the Duke criteria (Table 1). Of the 91 patients requiring surgical intervention, the majority of patients (85.7%) were diagnosed with native valve endocarditis (NVE). The aortic valve was most commonly infected in 61 (67.0%) patients followed by the mitral valve in 35 (38.5%) patients. As shown in Table 1, there was no difference in preoperative clinical characteristics between patients who survived compared with patients who died (in-hospital mortality rate 15.4%).


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  		Table 1. Clinical Characteristics of Total Population and According to Survival
 
The most common offending pathogen for both NVE and prosthetic valve endocarditis (PVE) was Streptococcus viridans followed by Staphylococcus aureus (Table 1). These two organisms accounted for approximately 75% of NVE cases. The virulent nature of S. aureus may account for the high proportion of patients found to have abscesses intraoperatively (> 30%) in our series. Staphylococcus epidermidis was identified in only three cases of PVE.

Indications for surgical intervention included new severe valvular regurgitation with heart failure, intracardiac abscesses, recurrent embolic events, and fungal endocarditis (Table 2). The most common echocardiographic finding leading to surgical treatment for both NVE and PVE was severe valvular regurgitation with intractable heart failure in 81 (89.0%) patients.


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  		Table 2. Indications for Surgery
 
All 91 patients underwent cardiopulmonary bypass with resection of the infected tissue followed by either valve repair or replacement. The choice between biological or mechanical prosthesis was made according to established guidelines, the patient's age, the need for long-term anticoagulation, and both surgeon and patient preference. Fifty-eight patients underwent replacement with a bioprosthesis, either a pericardial tissue valve (3) or homograft valve (55), while 22 patients underwent replacement with a mechanical valve (Table 3). Only 11 patients underwent valve repair in our surgical series (aortic valve [n = 6], mitral valve [n = 4], and tricuspid valve [n = 1]). Concomitant coronary artery bypass grafting was performed in 11 patients. The mean perfusion time and cross-clamp times for the total population were 171 ± 45 minutes and 131 ± 38 minutes, respectively.


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  		Table 3. Intraoperative Data
 
The postoperative clinical events are shown in Table 4. Overall, the rates of postoperative stroke, requirement for dialysis, and reoperation rate were less than 10%. The need for blood transfusion (greater than two units of packed red blood cells), prolonged ventilation as defined greater than 24 hours, and need for permanent pacemaker were significantly higher in patients who died compared with those who survived (p < 0.05). The need for permanent pacemaker implantation in the entire cohort was 24% (n = 22). Seventeen of these 22 patients had an aortic valve replacement and 5 patients had a mitral valve replacement. Additionally, of these 22 patients 15 had third-degree block and 7 had Mobitz type II second-degree block after surgery, prior to permanent pacemaker implantation.


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  		Table 4. Postoperative Clinical Events
 
As shown in Table 5, several preoperative ECG variables including first-degree block, interventricular conduction delay greater than 120 msec, and LBBB predicted the need for permanent pacemaker implantation on univariate analysis. Using a stepwise selection algorithm for model building with inclusion of age and gender, LBBB (p = 0.001) and low preoperative EF (p = 0.008) were the only independent predictors of pacemaker implantation.


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  		Table 5. Preoperative Electrocardiographic Variables Associated with Pacemaker Implantation
 
After age and gender adjustment, a preoperative EF less than 50% independently predicted mortality with a sensitivity of 92.3% and specificity of 95.7% (Tables 6, 7; Go Fig 1). The mean EF in those patients who died was 36 ± 7%. The presence of vegetation, size of vegetation, abscess, left atrial dilatation, and LV enlargement were not univariate predictors of in-hospital death.


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  		Table 6. Echo Variables Associated With In-Hospital Death
 

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  		Table 7. Predictive Accuracy of Preoperative EF for Postoperative Death
 

Figure 1
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  		Fig 1. Kaplan-Meier survival curves according to preoperative ejection fraction (EF).

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
The prompt identification of patients at high risk of developing complications, prolonged hospitalization, or death is important in the management of IE. The observation from this study is that simple preoperative cardiac investigations may allow the clinician to determine which patients may experience poor short-term clinical outcomes after surgery. A preoperative ECG demonstrating LBBB and a preoperative echocardiogram demonstrating LV dysfunction are independent predictors for the need for a permanent pacemaker postoperatively and in-hospital death, respectively.

High degree atrioventricular block occurs in 2% to 4% of all cases of infective endocarditis, carrying an increased risk of heart failure and death [2]. Conduction abnormalities are an early indication of an infectious process extending to involve the membranous interventricular septum, often a local extension of aortic valve endocarditis. If the infectious process enters the triangle of Koch, inflammation or destruction of the atrioventricular node and bundle of His will result in heart block. Previous studies on the permanent pacemaker requirements for patients with active IE are limited. Delay and colleagues [19] reported that permanent pacemaker implantation for atrioventricular block was a common complication after both NVE and PVE (12% to 15%). No correlation between preoperative ECG and subsequent pacemaker requirement was reported. The incidence of permanent pacemaker requirement in our population was somewhat higher at 24%. This difference probably reflects the high risk nature of the patients in a tertiary care setting.

The present study correlates preoperative ECG evidence of conduction disease with the requirement for permanent pacing in patients surgically managed for IE. Although the presence of LBBB had a low sensitivity of 40.9%, the specificity 98.5%, positive predictive value 90.0%, and negative predictive value 83.3% were high for subsequent permanent pacemaker insertion. In a cohort of patients with underlying LBBB and no structural heart disease, the incidence of developing progressive complete heart block is 1% to 2% [20]. In patients undergoing surgical debridement of the infectious nidus in the setting of structural heart disease, it is not unexpected to observe a high incidence of pacing requirements postoperatively as seen in our series. One year follow-up of ECGs in those patients requiring a permanent pacemaker postoperatively demonstrated that 90% had persistent advanced conduction abnormalities requiring pacing needs, reflecting the aggressive nature of the initial infective process. Of interest, although progressive conduction disease on serial ECGs serves as a marker of extension of the infectious process [2], neither aortic valve endocarditis nor the presence of an abscess in our population were independent predictors of pacing requirements postoperatively.

Reduced LV function on preoperative echocardiography served as an independent prognostic marker for in-hospital mortality. Echocardiography is the primary technique for the detection of vegetations and cardiac complications resulting from IE [21]. Echocardiography provides one of the major Duke criteria [3]. Three echocardiographic findings are considered to be major criteria for the diagnosis of endocarditis: (1) presence of vegetations defined as mobile echodense masses implanted in a valve or mural endocardium; (2) presence of abscess; or (3) presence of a new dehiscence of a valvular prosthesis [3, 22]. With the development of TEE imaging, the noninvasive detection of vegetations has substantially improved [23, 24].

Although echocardiography is widely used in the diagnosis and prognosis of IE, there is little available data regarding its ability to predict outcomes in the surgical cohort of patients with endocarditis. Wallace and colleagues [25] evaluated a number of clinical predictors of outcome in patients with infective endocarditis; and of interest, patients with poor LV function defined by echocardiography did not have a higher mortality at discharge or 6 month follow-up. Di Salvo and colleagues [26] clearly demonstrated that the presence and characteristics of vegetations on TEE is predictive of embolic events in patients managed for IE, but no evaluation of preoperative LV function and subsequent in-hospital mortality was reported. Recently, Thuny and colleagues [27] demonstrated that vegetation length greater than 15 mm was a strong predictor (relative risk = 2.1; 95% confidence interval [CI], 1.34 to 3.26; p = 0.001) of one year mortality in patients with endocarditis, but again no correlation between baseline LV function and mortality was reported.

A preoperative LV ejection fraction less than 0.50 in our patient population was an independent predictor of in-hospital mortality. The presence of a preoperative EF less than 0.50 had high sensitivity 92.3%, specificity 95.7%, PPV 80%, and NPV 98.5% for predicting in-hospital death. Other clinical settings in which a reduced left ventricular ejection fraction (LVEF) has clearly been demonstrated to have adverse prognostic implications include postmyocardial infarction, chronic heart failure due to ischemic or pre-coronary artery bypass grafting or valvular surgery [28–31]. The etiology of LV dysfunction in our patients, however, remained undefined. Whether the patient's LVEF less than 50% was preexisting prior to developing infective endocarditis or whether the reduction in overall LV function was a result of the acute infectious process could not be adequately assessed.

In our series, age, surgery, S. aureus infection, prosthetic valve, abscess, or aortic valve endocarditis were not significantly associated with mortality [9–19, 25–27]. This may reflect the changing spectrum of antibiotics, improved detection of complications with TEE, earlier intervention, and advances in surgical techniques. As the disease and its management have developed over the past decade, these variables may no longer be associated with poor short-term outcomes in the current era.

The primary limitation of this study is the small sample size and its retrospective nature. Even though this study population represents one of the largest of its kind in the current surgical management of IE [16–18], it remains small enough to be interpreted with caution. A larger prospective series or a multicentered approach may enable us to make more substantive conclusions regarding the roles of preoperative ECG and echocardiography in determining outcome measures in the surgical setting of active IE. In addition, due to the long recruitment period of ten years in our study, surgical techniques and antimicrobial therapy have evolved, opening the study to treatment biases. Nonetheless, the indications for surgical intervention in infective endocarditis remain unchanged.

Preoperative ECG findings of conduction disease and reduced left ventricular function on echocardiography are independent determinants of short-term morbidity and mortality that may allow for early risk stratification of this high risk population.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

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