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Ann Thorac Surg 1996;61:1217-1222
© 1996 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Infective Endocarditis: Ten-Year Review of Medical and Surgical Therapy

St. Vincent's Hospital and Medical Center and Oregon Health Sciences University, Portland, Oregon

Accepted for publication December 24, 1995.

	Abstract

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Infective endocarditis is a complex disease process. Optimal outcome often requires both medical and surgical expertise. The need for and timing of surgical intervention is controversial and continues to evolve in parallel to advancements in diagnosis and treatment. Our experience with the treatment of infective endocarditis is reviewed herein.

Methods. A retrospective review was compiled of 140 consecutive patients who fulfilled the modified von Reyn criteria for the diagnosis of endocarditis between January 1982 and April 1992.

Results. Patient characteristics, symptoms, and risk factors are described. Follow-up averaged 3.5 ± 0.8 years and totaled 491 patient-years. New York Heart Association functional class at presentation had a significant influence on survival (p< 0.0001). Long-term survival was significantly greater (p = 0.036) in patients treated medically/surgically than those treated with medical therapy alone (75% versus 54% at 5 years). Medical treatment of aortic and prosthetic endocarditis was associated with higher mortality (58% and 67%, respectively) when compared with combined medical/surgical treatment (28% and 38%, respectively). Among the survivors, New York Heart Association class at follow-up was better (p < 0.0001) in the medical/surgical group (1.05 ± 0.04) versus the medical treatment group (1.70 ± 0.14).

Conclusions. Combined medical/surgical treatment for infective endocarditis is associated with improved survival. Patients with aortic or prosthetic endocarditis are identified as subgroups that benefit most from surgical intervention. Valvular dysfunction incited by the infective process is an important factor that should be weighed carefully in the therapeutic decision.

	Introduction

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See also page 1222.

Endocarditis is a complex disease process associated with a high mortality. Considerable progress has been made since the preantibiotic era, when mortality approached 100%. The introduction of antimicrobial therapy reduced the mortality associated with endocarditis; however, valvular dysfunction and progressive heart failure continued to claim patient lives. In 1965, Wallace and associates [1] demonstrated the safety of valvular replacement in the face of active endocarditis, thereby reducing the mortality to its current level, 10% to 60% [2–5].

The management of patients with endocarditis is evolving in parallel to advancements in diagnosis as well as medical and surgical therapy. Without a doubt, both medical and surgical expertise is required to effect the optimal outcome. Currently, opinions vary widely in regard to the need for, timing of, and aggressiveness of surgical intervention[6–8]. To assess the long-term outcome of treatment within our institution, we undertook a retrospective review of our experience with endocarditis over a recent 10-year period.

	Material and Methods

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Between January 1982 and April 1992, 194 patients were admitted to St. Vincent's Hospital (Portland, OR) with the diagnosis of endocarditis. After retrospective review, 140 patients fulfilled the modified von Reyn criteria for the diagnosis of endocarditis [9, 10]. Data on these 140 patients were collected onto work sheets and entered into a database for statistical analysis (SPSS for Windows, Release 6.0; SPSS, Inc). Statistical differences between subgroups of patients were determined by ² analysis (nonparametric tests) and by analysis of variance (means comparison). Mean values are expressed as mean ± standard error throughout the article. Differences in survival were determined using the Kaplan-Meier log rank method or Cox regression analysis. Possible improvements in critical and postoperative care during the later part of the study are not accounted for and could affect the results presented.

Follow-up (93% complete) was obtained from the medical record or by direct telephone contact. The follow-up time was calculated as the period from diagnosis to last contact or death.

	Results

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Whole Study Population
The 140 patients had a male-to-female ratio of 1.86 and a mean age at diagnosis of 57.3 ± 2.9 years (range, 11 to 90 years). The spectrum of clinical presentation varied from minimal symptoms to florid congestive heart failure. This is reflected by a mean New York Heart Association (NYHA) functional class of 2.41 ± 0.18 at presentation, with 11.4% of patients (16/140) requiring inotropic support. Follow-up comprised 491 patient-years, with a mean of 3.5 ± 0.8 years.

Fever, malaise, weakness, fatigue, and rigors were the most frequent presenting symptoms:

Potential risk factors for the development of endocarditis varied widely:

Streptococcal species (58.7%) and Staphylococcus aureus (21.4%) were the most common organisms recovered by blood culture (Fig 1). The organism recovered had no effect on survival (p = 0.29) or the use of surgical therapy (p = 0.37).

View larger version (20K): [in this window] [in a new window]   Fig 1. . Microorganisms recovered by blood culture in 140 patients with infective endocarditis. ``Other'' category includes Propionibacterium, Haemophilus parainfluenzae, Actinomyces viscosus, Lactobacillus casei, Klebsiella pneumoniae, and Cardiobacterium (0.7% each). (Staph = Staphylococcus.)

Age, sex, site of valvular involvement, NYHA class at presentation, and mode of therapy were analyzed by Cox regression analysis. Only NYHA class at presentation (p < 0.0001) and mode of therapy (p = 0.0006) were identified as independent factors affecting survival.

Site of Valvular Involvement
The site of valvular involvement was determined by echocardiography as well as the surgical and autopsy findings (Fig 2). Left heart valvular endocarditis predominated (78.6%) in our study population. Right heart infection was uncommon (4.3%), and the site of infection could not be reliably localized in 17.1% of patients. Of note, aortic valve endocarditis was more likely to be treated with operation (p < 0.0001) than was mitral valve endocarditis (73% [32/44] versus 29% [17/59], respectively).

View larger version (22K): [in this window] [in a new window]   Fig 2. . Valve site involved as determined by echocardiography (medical treatment group) or by pathologic examination at the time of operation or autopsy. Note that the precise site of valvular involvement could not be accurately localized in 17.1% of patients.

View larger version (14K): [in this window] [in a new window]   Fig 3. . New York Heart Association functional class at presentation had a significant influence on survival (p < 0.0001) by Kaplan-Meier log rank method.

The presenting symptoms of the medical and medical/surgical groups did not differ significantly from those of the whole study population. Likewise, the demographic characteristics of both groups were similar. No significant differences in male-to-female ratio (2.36 versus 1.33; p = 0.11), age at diagnosis (58.4 ± 3.4 versus 55.7 ± 3.1 years; p = 0.36), NYHA class at presentation (2.31 ± 0.20 versus 2.55 ± 0.24; p = 0.16), and inotropic requirement at presentation (8.3% versus 16%; p = 0.15) were noted between the medical and medical/surgical groups, respectively. Mean follow-up time, however, was significantly (p = 0.014) longer in the medical/surgical group (4.4 ± 1.6 years) compared with the medical treatment group (2.9 ± 0.6 years); this is a reflection of the better long-term survival in the medical/surgical treatment group (see below).

There was no temporal bias in terms of the mode of therapy during the study period. In the first 5 years, 32 of 73 patients (44%) underwent operation as compared with 25 of 67 (37%) during the last 5 years of the study (p = 0.33).

The chosen mode of therapy had a significant influence on long-term survival (Fig 4). The combination of medical/surgical treatment was associated with better long-term survival (p = 0.036) than medical treatment alone. The differences in survival between the two groups were not realized acutely. Rather, the deviation in the survival curves became evident during the 3- to 24-month period after diagnosis.

View larger version (15K): [in this window] [in a new window]   Fig 4. . Long-term survival of medically/surgically treated patients (Med/Surg) was significantly better (p = 0.036) than that of medically treated patients (Medical) by Kaplan-Meier log rank method. Five-year survival was 75% (23 patients remaining) for the medical/surgical group and 53% (20 patients remaining) for the medical treatment group.

As noted above, NYHA class at presentation had a remarkable impact on survival. The significance of this relationship persisted within the medical/surgical treatment group (p = 0.035; log rank statistic = 8.6) and, even more so, in the medical treatment group (p < 0.0001; log rank statistic = 41.2) when analyzed by the Kaplan-Meier method.

The cause of death by mode of therapy is shown in Table 1. Death during active endocarditis and sepsis was markedly more frequent in the medical group than in the medical/surgical group (14 versus 1, respectively). Of the 14 septic deaths in the medically treated group, three occurred acutely (within a week of diagnosis), six as a result of medical treatment failure, and five after a recurrent episode of endocarditis/sepsis more than 6 months after initial presentation.

Prosthetic Valve Endocarditis
Prosthetic endocarditis comprised 22% (31/140) of our study population and was associated with a high mortality rate (56%, 17/31). Of the 31 patients, 18 were treated medically and 13 medically/surgically, with an overall survival of 33% and 62%, respectively (p = 0.044 by log rank test). The spectrum of microorganisms recovered by blood culture did not differ significantly from that of the whole study population (see Fig 1).

Additional Surgical Data and Results
The indications for operation were as follows: valvular dysfunction, 33; active endocarditis with valvular dysfunction, 15; active endocarditis alone, 6; and large vegetation on echocardiography, 3. In the 57 patients who underwent operation for endocarditis, 52 valve replacements (14 bioprostheses), 4 valvulo/annuloplasties, 2 native valve debridements, and 1 prosthetic valve debridement were performed. Annular or myocardial abscesses were encountered in 10 patients. Six of these patients had prosthetic valve endocarditis. Elective operation was performed in 51%, whereas the remainder were conducted emergently. No association between mortality and elective or emergent operation was observed (p = 0.22).

Recurrences
One (n = 16), two (n = 3), or more (n = 4) recurrent episodes of endocarditis developed in 23 patients during the study period. The initial therapy consisted of medical treatment alone in 22 of 23 of these patients (ie, only 1 patient had endocarditis 6 months after surgical therapy). Of the 22 patients whose initial management involved medical treatment, 7 underwent operation after recurrence, 10 received additional medical treatment, and 5 patients died as a direct result of the recurrence (22% mortality).

	Comment

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The treatment of infectious endocarditis has changed dramatically over the last 50 years. As advancements in antibiotic, critical care, and surgical therapies have evolved, the mortality of endocarditis has receded. Currently, improvements in treatment have focused on the timing of surgical intervention and the duration and efficacy of antimicrobial therapy [7, 8, 11]. The small number of patients treated at each individual institution makes prospective, single-institution trials prohibitive. Despite this, several groups have set forth general guidelines for treatment, which continue to be modified as additional data are collected, often retrospectively [6–8, 12, 13].

Endocarditis is a complex condition with a wide range of clinical presentations. The cardiovascular effects of sepsis present superimposed on a variable degree of valvular incompetence, thereby complicating decisions regarding the physiologic significance of the valvular dysfunction. With this in mind, those patients presenting without evidence of valvular compromise can be adequately treated with medical therapy alone in most cases. On the other end of the spectrum, patients with marked valvular insufficiency and severe heart failure require surgical intervention to remove the septic focus and restore valvular competence. Most authors agree that patients with annular or myocardial abscesses should be treated surgically [6, 14, 15]. A large group of patients remain with mild to moderate valvular dysfunction and variable degrees of septicemia. The timing and aggressiveness of surgical intervention in this group of patients remains less clear. The results of this study, however, provide additional information that may aid this difficult therapeutic decision.

The characteristics of our study population are comparable with those in other retrospective studies that use strict criteria for diagnosis [4, 10, 16, 17]. Likewise, the spectrum of microorganisms recovered (see Fig 1) and the sites of valvular involvement (see Fig 2) do not differ significantly from prior reports [10, 16, 17]. The degree of heart failure at presentation had a profound influence on survival (see Fig 3). This confirms the findings of previous studies [14, 18, 19].

Long-term survival of patients treated with a combined medical/surgical approach was significantly better than that of those treated with medical therapy alone (see Fig 4). This finding reiterates the reports of earlier investigators. Griffin and colleagues [20] reported a lower mortality in patients treated with a combined medical/surgical mode (20%) as compared with medical therapy alone (61%). Croft and associates [21] reported mortality rates of 11% and 56%, respectively, for medical/surgical therapy versus medical therapy alone. Similarly, Mills and co-workers [19] and Richardson and colleagues [22] demonstrated notable reductions in mortality when operative intervention was added to the medical regimen. These antecedent studies ascribe the more favorable outcome of combined medical/surgical therapy to improved valvular function and, hence, the avoidance of worsening heart failure. This appears to be the case in our study as well for the following reasons. First, deviation of the survival curves for the two groups occurs not during the acute presentation but instead during the 3- to 24-month interval after the diagnosis (see Fig 4). Progressive heart failure from valvular dysfunction would be most prevalent in this time period. Second, the medical/surgical group enjoyed more than a full category improvement in NYHA functional class from the time of presentation to follow-up. In sharp contrast, the medical group experienced no change in NYHA class from presentation to follow-up despite a similar NYHA class at presentation in both groups. This observation reflects the treatment of valvular dysfunction in the medical/surgical group. In further support of this contention, the overall NYHA class at follow-up was significantly better in the medical/surgical group (1.05 ± 0.04) when compared with the medical group (1.70 ± 0.14). Therefore, a mild to moderate degree of tolerable heart failure persists in the surviving patients of the medical treatment group. Finally, if valvular dysfunction has an influence on long-term survival, surgical therapy should decrease that association by treating the valvular dysfunction. This effect was assessed by examining long-term survival versus NYHA class at presentation in both groups. Indeed, the association between survival and NYHA class at presentation was less in the surgical group (p = 0.035; log rank statistic = 8.6) than in the medical group (p < 0.0001; log rank statistic = 41.2). In summary, the enhanced survival associated with combined medical/surgical therapy probably reflects the timely identification and treatment of the valvular dysfunction incited by the infective process. Therefore, the decision to intervene surgically in a patient with endocarditis should take into account the degree of valvular incompetence at the time of presentation as well as an understanding that valvular insufficiency may progress after discharge on medical therapy alone.

The distinction between aortic and mitral valve endocarditis requires further comment. Aortic valve endocarditis is a much more malignant process than the mitral valve counterpart [14, 17, 23]. Aortic valve incompetence is more frequently associated with heart failure and is less effectively managed medically than mitral valve incompetence, especially in the acute setting [12, 14, 17]. The results of our study support this distinction. Indeed, aortic endocarditis was more often managed surgically (73%) than was mitral endocarditis (29%). In addition, the mortality of medically managed aortic endocarditis was twice (58%) that of combined medical/surgical treatment (28%; p = 0.04). Other investigators have also observed that surgical intervention is more frequently implemented in aortic than mitral valve endocarditis [14, 17] and that aortic endocarditis is more often complicated by heart failure [12, 23]. Therefore, the subset of patients with aortic endocarditis accompanied by valvular dysfunction should benefit the most from surgical intervention.

Patients with prosthetic endocarditis is another subgroup of patients who benefit from surgical therapy (see Results). Mortality is higher (67%) in those treated medically as compared with those treated with combined medical/surgical therapy (38%; p = 0.044). Others [24] have made similar conclusions.

The management of infective endocarditis continues to evolve as additional data are analyzed and the intricacies of the disease process unfold. In support of earlier studies [19–22, 25], our series demonstrates improved survival with a combination of medical/surgical therapy. The difference is attributed to more effective treatment of valvular dysfunction and the resulting prevention of progressive heart failure. Clearly, the data are all retrospective and not controlled. The possibility remains, however, that surgical intervention may improve survival. If surgical intervention is applied liberally, many patients would undoubtedly undergo operation unnecessarily. The further definition of patients who would benefit from operation, and the optimal timing of operation, are future challenges. Current data, however, are sufficient to discourage medical management of prosthetic endocarditis and aortic endocarditis complicated by valvular dysfunction. Patients with symptoms of mild to moderate congestive heart failure who are treated medically require close follow-up as progressive valvular dysfunction appears to contribute to the late mortality observed in this subgroup of patients.

	Acknowledgments

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	References

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Angelo A Vlessis Hagop Hovaguimian James Jaggers Aftab Ahmad Albert Starr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vlessis, A. A Articles by Starr, A. Search for Related Content PubMed PubMed Citation Articles by Vlessis, A. A Articles by Starr, A. Related Collections Related Article