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Ann Thorac Surg 2001;71:1874-1879
© 2001 The Society of Thoracic Surgeons


Original article: cardiovascular

Double valve endocarditis

A. Marc Gillinov, MDa, Ramon Diaz, MDa, Eugene H. Blackstone, MDa, Gösta B. Pettersson, MDa, Joseph F. Sabik, MDa, Bruce W. Lytle, MDa, Delos M. Cosgrove, III, MDa

a Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

Accepted for publication February 22, 2001.

Address reprint requests to Dr Gillinov, Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, F25, 9500 Euclid Ave, Cleveland, OH 44195
e-mail: gillinom{at}ccf.org


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. There are little data concerning surgical outcomes in patients with native valve endocarditis affecting both the aortic and mitral valves.

Methods. From 1977 to 1998, 54 patients had simultaneous aortic and mitral valve grafting for native valve endocarditis. In 78%, mitral valve involvement was limited to the anterior leaflet, suggesting a jet lesion from the aortic valve. Surgical strategies included 31 valve repairs and valve replacement with mechanical (34), bioprosthetic (34), or allograft (9) prostheses. Three hundred twenty-five patient-years of follow-up were available for analysis (mean 6.0 ± 4.8 years).

Results. There were no hospital deaths. Ten-year survival was 73%. Ten-year freedom from recurrent endocarditis was 84%, with risk peaking at 3 months, followed by a constant risk of 1.3%/yr. Choice of valvar procedure did not influence mortality or reinfection risk.

Conclusions. The most common pattern of double valve infection was a jet lesion on the anterior mitral leaflet. Surgical treatment has late survival and freedom from reinfection similar to those of patients with single heart valve infection.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Surgical treatment of native valve endocarditis (NVE) involving either the aortic or mitral valve is well described, with excellent results reported with both valve repair and valve replacement [15]. There is little information, however, concerning patients with NVE that affects simultaneously both the aortic and mitral valves. The purpose of this study was to determine the pathology, surgical strategies, and outcomes of patients with double valve endocarditis.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Patients
From 1977 to 1998, 54 patients with NVE affecting both the aortic and mitral valves underwent valvar heart procedures. Mean age was 50 ± 15 years (range, 17 to 77 years); 76% were men. At the time of operation, 7% were in New York Heart Association functional class I, 65% in class II, 13% in class III, and 15% in class IV. Left ventricular function was normal in 74% of patients.

The diagnosis of aortic and mitral valve endocarditis was made using standard criteria [6, 7]. In patients with preoperative echocardiograms, the Duke criteria for diagnosis were applied [8]. Endocarditis was considered to be active when these conditions were met and operation was undertaken within 2 months of diagnosis or in the presence of signs of active infection by macroscopic or microscopic findings at the time of operation or by culture from operative specimens [6]. Characteristics of the patients and the infection are detailed in Tables 1 and 2. Endocarditis was active in 50% and remote/healed in 50%. Responsible organisms were predominantly Streptococcal species, Staphylococcal species, and Hemophilus species. Probable sources of infection were identified in 22 patients, with 11 infections attributed to dental sources. Aortic involvement included multiple cusps in 17 patients. Seventy-eight percent of patients had 3 or 4+ aortic regurgitation, and 70% had 3 or 4+ mitral regurgitation. In 14 patients with anterior mitral leaflet involvement, a "windsock" lesion was observed. No patient had contiguous spread from one valve to another or involvement of the fibrous trigones. Four patients had extension to the conduction system, and 2 patients had intracardiac fistulas.


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Table 1. Characteristics of Double Valve Endocarditis

 

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Table 2. Clinical Presentation of Patients With Double Valve Endocarditis

 
The primary indication for operation was congestive heart failure in 83% of patients. Other manifestations of endocarditis included persistent sepsis (35%) and systemic emboli (15%). Operation was performed electively in 78% and urgently or emergently in 22%. Infected material was debrided aggressively in all patients.

Table 3 lists the valvar procedures performed. In 41% of patients, mitral valve repair was performed, including 33% of patients with active endocarditis and 48% of patients with remote endocarditis. Mitral valve repair has become increasingly the norm in more recent years (Fig 1A). A variety of mitral repair techniques were used, with pericardial patch repair of the anterior mitral leaflet being the most commonly applied technique (Table 4). Only one-half of patients having mitral valve repair had an annuloplasty. Aortic allografts have recently become the prosthesis of choice for management of the aortic valve infection (Fig 1B). Additional cardiac procedures included coronary artery bypass grafting (6 patients), tricuspid valve repair (1 patient), arch aneurysm repair (1 patient), and myectomy (1 patient).


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Table 3. Valvar Procedure in 54 Patients With Double Valve Endocarditis

 


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Fig 1. Trends in surgical management of the mitral and aortic valves in double valve endocarditis. The patients have been lumped with 3-year intervals, and the percentages refer to the 3-year totals. (A) Use of mitral valve repair. The logistic p for trend over calendar time was 0.007. (B) Use of allograft as aortic prosthesis. The logistic p for trend with calendar time was 0.005.

 

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Table 4. Mitral Repair Techniques in 22 Patients With Double Valve Endocarditis

 
When possible, the diagnosis of recurrent endocarditis was made using standard criteria [6, 7]. Three patients received treatment for recurrent endocarditis at outside hospitals. Although records from these hospitals were obtained and reviewed, the infecting organism was not specified in 2 patients and the affected valves unspecified in 1 patient. In each patient, however, the treating physicians concluded that the patient had endocarditis, and therefore, we have included these patients in the analysis of recurrent endocarditis. Although we use the term recurrent endocarditis, it is possible that some of these patients, particularly those with incomplete documentation, may represent persistent infection rather than a new infection.

Follow-up
Follow-up was obtained by direct contact with the patient, referring physician, or both. One patient was lost to follow-up after hospital discharge. There were 325 patient-years of follow-up available for analysis, and mean follow-up interval was 6.0 ± 4.6 years. In 44% of patients, follow-up exceeded 5 years, and in 16% it exceeded 10 years. Although follow-up extended as long as 18 years, time-related events will be presented only to 12 years, at which time only 4 patients were being traced.

Methods of analysis
Events after operation (death, recurrent endocarditis, and reoperation) were analyzed in a time-related manner. Nonparametric estimates were obtained by the method of Kaplan and Meier, and are presented with asymmetric confidence limits (CL) equivalent to one standard error (68%) [9]. A parametric method was used to resolve the number of phases of instantaneous risk of events (hazard functions) and to estimate their shaping values [10]. Both the parametric and hazard function estimates are presented with confidence limits equivalent to one standard error (68%) [10].

Multivariable analyses were performed in the hazard function domain. We recognize that likely at most one factor could be resolved per outcome event. For these analyses, we examined the following variables: demography (age, sex); clinical status at operation (New York Heart Association functional class, surgical priority—elective, urgent, emergent); features of the endocarditis (active versus inactive, staphylococcal organism versus others, documented dental origin); valve pathology (presence of vegetation, abscesses, perforations, and identification of the cusp or leaflet involved in both aortic and mitral valve locations); operative details (repair versus replacement, and if replacement, prosthesis type separately for aortic and mitral locations); experience (date of operation). The p value criterion for retention of variables in the final models was 0.1.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Hospital morbidity and mortality
There was no hospital or 30-day mortality (0%; CL 0%–3.5%). In-hospital morbidity included stroke in 5 patients (9%; CL 5%–15%), reoperation for bleeding in 8 patients (15%; CL 10%–22%), renal failure in 1 patient (2%; CL 0.2%–6%), and respiratory failure in 4 patients (7%; CL 4%–13%). Of the 8 patients who required reoperation for bleeding, 7 had active endocarditis and 1 underwent urgent or emergent operation.

Survival
There were 9 late deaths, and 10-year actuarial survival was 73% (Fig 2). Eight deaths were of cardiac origin, and 1 patient died of pneumonia. Two patients that died had recurrent endocarditis. One had infection of aortic and mitral bioprostheses and died at an outside hospital without operation. The other died after reoperation for recurrent endocarditis. Multivariable analysis demonstrated that increasing patient age (p = 0.004) and earlier date of operation (p = 0.02) decreased late survival. Pathologic findings and choice of valvar procedure could not be demonstrated to influence patient survival.



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Fig 2. Survival after operation for double valve endocarditis. Each circle represents a death, positioned on the vertical axis according to the Kaplan-Meier estimation. The solid curve is the parametric estimate. Vertical bars and confidence bands are 68%, equivalent to one standard error. The number of patients traced across time is shown in parentheses.

 
Recurrent endocarditis
Seven patients developed recurrent endocarditis (Table 5), and 10-year freedom from recurrent endocarditis was 84% (Fig 3A). The risk of recurrent endocarditis peaked 3 months after operation, and then decreased to a constant risk of reinfection of 1.3% per year (Fig 3B). Of the 7 patients with recurrent endocarditis, 4 patients had involvement of both valves and 2 patients had only mitral valve involvement; in 1 patient, outside records stated that the patient had endocarditis but failed to identify the valves affected. Three patients were infected with the original organism, and 1 patient with a new organism; in 3 patients either the original or reinfecting organism could not be identified by records obtained from referring hospitals. Four of the 7 patients were managed by reoperation, one of whom died (discussed previously), and 3 patients were treated with antibiotics alone, one of whom died (discussed previously).


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Table 5. Recurrent Endocarditis

 


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Fig 3. Freedom from recurrent endocarditis. The depiction is formatted as in Figure 2. (A) Freedom. (B) Hazard function with expanded horizontal axis.

 
By multivariable analysis, no risk factors for recurrent endocarditis could be demonstrated. Specifically, choice of valvar procedure and active endocarditis did not influence demonstrably freedom from recurrent endocarditis.

Reoperation
Nine patients underwent cardiac reoperation, and 10-year freedom from reoperation was 73% (Fig 4). Reasons for reoperation included endocarditis (4 patients), bioprosthetic valve degeneration (4 patients), and heart transplant for cardiomyopathy (1 patient). Only 1 of 22 patients having mitral valve repair required late reoperation (p = 0.02 versus bioprosthetic mitral replacement by log-rank test).



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Fig 4. Freedom from reoperation. The depiction is formatted as in Figure 2. (A) Freedom. (B) Hazard function.

 

    Comment
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
This study confirms previous observations concerning pathology in patients with simultaneous infection of the native aortic and mitral valves. The most common pattern of double valve infection includes a jet lesion on the anterior mitral leaflet; contiguous spread of infection, and involvement of the fibrous skeleton of the heart are rare. This pathology is favorable for surgical management, as infections that extend to the fibrous skeleton of the heart require complex operations with high operative morbidity and mortality. There were no hospital deaths in this series. Although patients in this study had infection of two valves, late survival and freedom from reinfection were similar to those observed in patients undergoing operation for infection of only one heart valve. Thus, surgical therapy results in excellent early and late outcomes in these patients.

Although antibiotic therapy is often effective at treating NVE, operation is necessary in 20% to 40% of patients [6, 1113]. The indications for surgical therapy are well established, with congestive heart failure being the most common indication for operation [6, 14]. In recent years, we have taken an increasingly aggressive approach to early surgical intervention in patients with NVE and important valvular dysfunction, thromboemboli, or persistent sepsis. Certain groups of patients, including those with hemodynamic compromise and severe aortic insufficiency, derive particular benefit from early surgical intervention [6, 13, 15]. In such patients, the duration of preoperative antibiotic therapy does not influence the timing of surgical intervention.

Although the role of operation in patients with NVE is clear, the choice of valvar procedure remains controversial. Occasionally infected aortic valves can be repaired. Aranki and coworkers [16] reported excellent results using standard prostheses to replace infected aortic valves. However, for aortic valve endocarditis, particularly when accompanied by aortic root involvement, allograft aortic valve replacement has distinct advantages. Demonstrated benefits to the allograft in this setting include a low and constant risk of recurrent endocarditis and decreased operative mortality [1719]. In addition, technical factors favor the allograft in the presence of aortic root abscess or destruction. There has also been enthusiasm for application of the Ross procedure in patients with aortic valve endocarditis [20, 21]. This option has the advantage of placing living tissue in the aortic position, and, to date, this strategy has been associated with a low risk of reinfection [20, 21].

Surgical treatment options for NVE affecting the mitral valve include valve replacement and valve repair. Although there is some experience with the mitral valve allograft for treatment of mitral valve endocarditis, there are too little data available to support this strategy [22]. In contrast, several reports confirm the efficacy of mitral valve repair in patients with both active and healed NVE [35]. In this setting, mitral valve repair is associated with low operative mortality, low risk of reinfection, and low incidence of reoperation. Therefore, when feasible, mitral valve repair is the procedure of choice for surgical treatment of NVE affecting the mitral valve.

Operative mortality in patients with NVE ranges from 0% to 10% [15, 1116]. Documented risk factors for increased operative mortality include nonstreptococcal infection, increasing New York Heart Association functional class, renal failure, increased age, cardiogenic shock, failure to use an allograft for aortic valve endocarditis, and mitral valve replacement instead of mitral valve repair for mitral valve endocarditis [2, 4, 11, 19, 22]. Late survival in these patients is good, with 5-year survival of approximately 80% and 10-year survival of approximately 60% [1, 2, 13, 15].

Persistent or recurrent infection is the most important morbid event after operation for NVE. Ten-year freedom from recurrent endocarditis after operation for NVE is approximately 80% [2, 16, 17, 19]. Active infection and staphylococcal infection increase the risk of recurrent endocarditis, whereas use of an allograft valve in the aortic position and mitral valve repair decrease the risk of reinfection [35, 18]. Although choice of valvar procedure has a modest impact on results, excision of all infected material is the cornerstone of treatment in these patients [6].

Until now, there have been little data describing pathology, surgical strategies, and results in patients with endocarditis affecting both the native aortic and mitral valves. Approximately 10% of patients with endocarditis have simultaneous aortic and mitral valve infection [1, 3, 9, 12, 13, 15, 23, 24]. Aortic valve endocarditis is generally the primary event. The most common pathologic finding is aortic valve endocarditis with an associated lesion on the anterior leaflet of the mitral valve [6, 25, 26]. The lesion on the anterior mitral leaflet may be a vegetation, aneurysm, or frank perforation. The pathogenesis of the mitral valve lesion is thought to involve a jet of aortic regurgitation that produces an infected lesion on the anterior mitral leaflet. Other less common mechanisms of anterior leaflet mitral valve involvement in patients with aortic valve endocarditis include repeated impingement of a prolapsing aortic vegetation on the anterior mitral leaflet and direct extension of infection along the mitral–aortic intervalvular fibrosa [26]. Although direct extension and involvement of the fibrous skeleton of the heart has been reported in NVE, it is exceedingly rare in this setting and was not present in any of the 54 patients in this series.

The most common approach to double valve endocarditis has been replacement of both valves [2426]. In the current series, 41% of mitral valves and 17% of aortic valves were repaired. Repair is most applicable to the mitral valve, and in recent years we have become increasingly aggressive with mitral valve repair in the setting of endocarditis. Perforations are patched with autologous pericardium. If there is active infection and the annulus is dilated, an annuloplasty is performed with autologous or bovine pericardium and polypropylene suture; otherwise, no annuloplasty is included. On the basis of data from Haydock [17], Agnihotri [18], and McGiffin [19] and their colleagues, we favor allograft aortic valve replacement for aortic valves that are not amenable to repair. This is a recent change in our practice, which accounts for the small number of allografts in this report.

Results of operation for NVE affecting the aortic and mitral valves were gratifying. There was no operative mortality, and operative morbidity was low. This may be attributable in part to the fact that 50% of patients had remote endocarditis and the majority of patients had elective operation. Ten-year survival was 73%, which is similar to that for endocarditis affecting a single native valve [2, 13, 15]. Ten-year freedom from recurrent endocarditis was 84%, which is also similar to that reported for single valve endocarditis [2, 16, 17, 19]. Small numbers of patients limited our ability to determine risk factors for late mortality and recurrent infection. Nevertheless, data from previous series of patients with single valve endocarditis support a strategy of aggressive debridement, valve repair when possible, and allograft replacement of the aortic valve when repair is not feasible.

This is a clinical study of a relatively small number of patients. This limitation may be responsible for our inability to demonstrate outcome differences between patients with active and remote endocarditis or superiority of one surgical technique over another.

In conclusion, the most common pattern of double native valve infection includes a jet lesion on the anterior mitral leaflet. A surgical strategy that uses valve repair whenever feasible is suggested. Surgical treatment of double valve endocarditis is accompanied by good early results and late survival and freedom from recurrent infection that are similar to those found in patients with infection of only one valve.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

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