Aortic valve endocarditis represents one of the leading causes of operative mortality in cardiac surgery, ranging from 8% to 37%.1–3 Poor outcomes are related to drug resistance, delay in surgical treatment, presence of concomitant risk factors and multiple end organ dysfunction, acute congestive heart failure (CHF), prosthetic valve reinfection, and severity of valve injury.4–6 After initiation of antibiotic therapy, early surgical intervention is usually recommended especially when complications such as severe CHF, presence of large vegetations, annular abscesses, fistula formation, and cerebral embolization occur.1 In these cases, aortic valve replacement remains the standard surgical approach.6 Previous studies have identified emergency operations, age, atrial fibrillation, acute aortic insufficiency, cardiopulmonary bypass time, and cross-clamp time as risk factors for aortic valve surgery in patients with endocarditis.7 In an attempt to improve surgical outcomes and reduce the risk of prosthetic valve reinfection, alternative procedures, such as aortic valve repair, implantation of homografts, autografts (Ross procedure), or stentless bioprosthetic valves, have been proposed.8–10 However, the benefits of these methods on surgical outcomes are unclear, and their role remains debated.8
Despite recent advances, surgical results of aortic valve surgery for endocarditis remain generally poor.1–7 The reasons are multifactorial and related to the patients’ compromised preoperative state. Postoperative deterioration of left ventricular (LV) function could contribute to this process, as previous series of patients with degenerative aortic valve disease have shown significant deterioration of LV function after aortic valve surgery.11,12 It is possible that postoperative deterioration of LV function after aortic valve surgery for endocarditis could play an additive role with other clinical variables (such as sepsis, respiratory failure, multiorgan dysfunction, etc.) in increasing postoperative morbidity and mortality.
In an attempt at preserving myocardial function and limiting the extent of myocardial ischemic injury during aortic valve surgery for endocarditis, we have used a technique of myocardial protection that entails continuous myocardial normothermic perfusion without cardioplegic arrest and myocardial ischemia (beating-heart technique).13–15 The aim of this article is to report our initial clinical experience with the beating-heart technique in a complex cohort of patients with infective endocarditis requiring aortic valve surgery, and to discuss its potential advantages.
From June 2000 to November 2007, a total of 30 consecutive patients with aortic valve endocarditis underwent surgery at our institution and were included in this review. Institutional review board approval for this study was obtained to retrospectively review the medical records of these patients, waiving the need for informed consent. All patients underwent aortic valve surgery utilizing the beating-heart technique, with implantation of either a mechanical or a biologic valve.
The patients’ preoperative clinical characteristics are summarized in Table 1. There were eight patients (26.6%) with prosthetic valve endocarditis, and 22 patients (73.3%) with infection of the native aortic valve (mean age 52.8 ± 16.1 years). One patient (3.3%) had a prior coronary artery bypass grafting. These operations were categorized as elective in one patient (3.3%), urgent/emergent in 22 patients (73.3%), and “salvage” in seven patients (23.3%). Salvage procedures are defined in the “Definitions” section of this article.
All patients were evaluated preoperatively for risk factors, and other relevant clinical variables were noted. Preoperatively, two patients (6.6%) had history of recent stroke due to brain embolism and three (10%) had renal failure. Twelve patients (40%) presented with CHF, eight patients (26.6%) with septic shock, and five patients (16.6%) with respiratory failure. The etiology of the infection was identified in 15 patients (50%), as shown in Table 1. Infections caused by Staphylococcus species and Enterococcus species were the most common, involving 26.6% and 13.3% of the patients, respectively.
A detailed description of the surgical technique for beating-heart aortic valve surgery has been reported by our group elsewhere.13,15 In brief, all procedures were performed at systemic temperature of 34°C–35°C. After heparinization, the ascending aorta and right atrium were cannulated, except in patients with concomitant mitral valve disease, in whom bicaval cannulation was performed. The coronary sinus was cannulated with a self-inflating coronary sinus balloon catheter, and encircled with a 4-0 prolene suture from the outside of the heart to prevent catheter dislodgment, as previously described.16 In most patients, the right superior pulmonary vein was cannulated for LV venting. As the aorta was cross-clamped and coronary sinus perfusion with warm blood (mean pressures of 50–55 mm Hg and flows greater of 250–300 mL/min) was commenced, a transverse aortotomy was performed with the heart beating. Using the side port of the aortic cannula as inflow, a “Y” cannula was connected to two coronary perfusion catheters (Polystan AS, Denmark). The two catheters were inserted into the left and right coronary ostia and were used to perfuse the heart in an antegrade fashion simultaneously with retrograde perfusion via the coronary sinus. In rare cases, the right coronary ostium could not be cannulated, and myocardial perfusion was provided via the left coronary and the coronary sinus. The remainder of the surgery proceeded as in any other aortic valve procedure. Blood obscuring the operative field was removed by increasing suction in the LV vent or by placing a sump catheter though the aortic annulus. As the aortotomy was closed, antegrade perfusion catheters were removed, maintaining the myocardium perfused via the retrograde route. The aortic cross-clamp was then removed, restoring normal myocardial perfusion.
When concomitant mitral valve surgery was required, the technique was modified as described previously.17 In these cases, bicaval cannulation and trans-septal approach were used to expose the mitral valve. The coronary sinus catheter was placed under direct vision through the right atrium. In rare cases (absence of aortic insufficiency), the mitral valve procedure was performed first providing continuous myocardial normothermic perfusion through the aortic root and the retrograde coronary sinus catheter, while aortic valve replacement followed as described above. In most patients (because of severe aortic insufficiency), the aortic root was opened first and the coronary ostia cannulated for antegrade perfusion, after which mitral valve surgery was performed with the heart perfused simultaneously through the coronary ostia and the retrograde coronary sinus catheter. Aortic valve surgery was then performed as described above.
Ventricular fibrillation did not occur during simultaneous antegrade/retrograde perfusion of the myocardium with warm blood because we ensured that adequate perfusion flow and temperature were being used throughout the procedure. Should ventricular fibrillation occur, the heart can be defibrillated and the surgeon must ensure that adequate myocardial flows are being delivered, increasing flows to the heart if possible. During normothermic perfusion with blood via antegrade and retrograde routes, myocardial ischemia is avoided and, therefore, we expect the heart to remain in sinus rhythm throughout the perfusion period, or in atrial fibrillation should the patient be in atrial fibrillation preoperatively.
Definitions and Statistical Analysis
The Duke criteria18 were used to define the diagnosis of aortic endocarditis. Early mortality and late mortality were defined as death occurring within 30 days of the operation or after 30 days, respectively. Heart failure was classified according to the New York Heart Association classification guidelines from I to IV, as shown in Table 1. Renal failure was defined as renal dysfunction resulting in a creatinine level ≥2.0 mg/dL. Regarding the operative procedure classification, “urgent” and “emergent” operations were defined as those performed within 24 hours of cardiac surgical consultation because of severe CHF from aortic valve dysfunction or large vegetations. Salvage operations were defined as those performed under extreme conditions, ie, in critically ill patients with at least two of the following conditions: ventilator dependency, cardiogenic shock, severe metabolic acidosis, septic shock, recent history of cardiac arrest and cardiopulmonary resuscitation, end-stage renal disease, and liver failure.
Variables of LV systolic function, LV dimensions, and left atrial dimension were investigated by transthoracic echocardiography according to the recommendations made by the American Society of Echocardiography.19 Parameters measured included LV ejection fraction (EF), LV fractional shortening (FS), LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD), and left atrial (LA) diameter. FS was measured by M-mode examination of the LV using short axis diameters based on the formula: FS= [(end diastolic − end systolic)/end diastolic] × 100(%).20 The presence of aortic regurgitation, stenosis, and valve vegetations were noted. The severity of aortic regurgitation was assessed by standard semi-quantitative methods using color Doppler. Aortic regurgitation was graded as mild, moderate, or severe. Numerical values were expressed as mean ± SD. Statistical comparisons between selected preoperative and postoperative values were made by using the paired t test. P values of less than 0.05 were considered significant.
Nineteen patients (63.3%) had isolated aortic valve endocarditis, whereas nine patients (30%) had both aortic and mitral endocarditis. Nine patients (30%) had aortic root abscesses and five patients (16.6%) also had mitral valve annular abscesses. Two patients (6.6%) had intracardiac fistulae, one from aorta to the right atrium, and the other from the aorta to the left atrium. Preoperative echocardiographic data and surgical procedures are summarized in Table 2. All patients had echocardiographic evidence of vegetations involving the aortic valve apparatus, and four patients (13.2%) had annular abscesses. Aortic insufficiency was graded as shown in Table 2. Aortic biologic prostheses were used in 25 patients (83.3%), whereas mechanical prostheses were used in four (13.3%) patients. One patient (3.3%) had a valve repair procedure. Mean prosthetic aortic valve size was 22.5 ± 1.9 mm (range 21–25 mm).
Eight patients (26.6%) had redo procedures. Annular reconstructive procedures with bovine pericardium were required in four patients (13.2%) due to extensive annular destruction by abscesses. Concomitant procedures included mitral valve replacement in nine patients (30%), mitral valve repair in five patients (16.6%), tricuspid valve surgery in two patients (6.6%), and coronary artery bypass grafting in one patient (3.3%) (Table 2). In patients requiring concomitant mitral valve surgery, the mean mitral prosthesis size was 28.1 ± 1.8 mm (range 25–33 mm). Patients requiring concomitant mitral valve surgery had been included in a previous report on beating-heart multiple valve surgery.21
Table 3 summarizes the operative and postoperative data. Total CPB time was 125 ± 67 minutes, and cross-clamp time was 81 ± 44 minutes. Postoperative low cardiac output state requiring intra-aortic balloon pump support was observed in one patient (3.3%). Two patients (6.6%) sustained a stroke postoperatively; however, neither case was related to air embolism during the operative procedures. Two patients (6.6%) required a tracheostomy because of the need for long-term mechanical ventilation. The mean length of hospital stay was 29 ± 20 days (range 5–72).
Table 4 summarizes postoperative and follow-up data. Mean clinical follow-up was 7.9 ± 12 months (range 1–56). The observed early mortality (30 days) was 13.3% (four patients), whereas late mortality was 10% (three patients). Combined early and late mortality was 42.8% (three of seven patients) in salvage operations, and 18.1% (four of 22 patients) in urgent/emergent cases. Similarly, total mortality increased from 12.5% (two of 16 patients) in patients with isolated aortic valve endocarditis to 35.7% (five of 14 patients) in patients with aortic and mitral valve endocarditis.
Figure 1 shows that there was no statistically significant difference between preoperative and postoperative LV EF and FS. EF was 52.6 ± 11.8% preoperatively and 54.3 ± 11.9% postoperatively (P = 0.61), whereas FS was 34.4 ± 12.8% preoperatively compared with 32.4 ± 10.4% postoperatively (P = 0.56). Figure 2 shows that LVEDD decreased from a preoperative value of 4.4 ± 1.3 cm to a postoperative value of 4.0 ± 1.4 cm (P = 0.03). Conversely, there was no statistically significant difference between preoperative and postoperative LVESD and LA dimension (P = 0.26 and P = 0.07, respectively).
Surgery for endocarditis of the aortic valve remains associated with significant morbidity and mortality.1–7 Patients with aortic endocarditis frequently have several comorbidities and multiple end organ involvement. Extensive destruction of the aortic leaflets by the infectious process can result in acute aortic insufficiency, which is often poorly tolerated. When the annulus of the aortic valve becomes involved, the development of abscesses and annular destruction may lead to heart block and intracardiac fistula. These can further increase the complexity of the operation and, consequently, surgical mortality. Although early surgery in patients with infection confined to the aortic leaflets and without annular involvement can lead to improved outcomes,8 the prognosis of this disease remains generally poor.1–7 The reasons are multifactorial and include the patients’ compromised preoperative state. The heterogeneity of preoperative, operative, and postoperative variables makes it difficult to establish the relative contribution of each factor to poor outcomes.
Recent reports from the literature on aortic valve endocarditis have largely focused on the surgical strategy and operative repair options. Complete debridement of the aortic root is an important component of the surgical therapy.8 However, there is controversy as to the ideal aortic valve substitute (homograft, autograft, or conventional biologic and mechanical prostheses). It has been suggested that homografts, autografts, and stentless valves may be more resistant to reinfection, especially in the presence of annular abscesses, although they generally involve increased surgical complexity.22–25 Recent reports suggest that conventional prostheses (either biologic or mechanical) are viable options in patients with aortic endocarditis.26–28
Postoperative deterioration of LV function could also contribute to postoperative morbidity and mortality in patients with endocarditis. Previous reports of patients with degenerative aortic valve disease have shown that deterioration of LV function can occur after aortic valve surgery.11,12,29,30 Some studies have shown that the magnitude of postoperative LV dysfunction correlates with the severity of preoperative LV dysfunction and ventricular hypertrophy, some of which may be reversible after surgery.11,12 Unfortunately, the potential role of LV functional deterioration after aortic valve surgery for endocarditis has remained largely unexplored. Ischemia-reperfusion injury produced during surgery by cardioplegic arrest could play a role in this process, especially in double-valve procedures and complex operations requiring prolonged periods of aortic cross-clamping.
To preserve myocardial function and limit the extent of myocardial ischemic injury, we used a technique of myocardial protection that entails continuous antegrade and retrograde myocardial normothermic perfusion, avoiding cardioplegic arrest and myocardial ischemia (beating-heart technique). Experimental studies by our group31,32 demonstrated decreased accumulation of extracellular fluid, diminished lactate production, and greater preservation of high energy stores when a strategy of myocardial protection with simultaneous antegrade/retrograde continuous normothermic, normokalemic blood perfusion was used as compared with conventional cardioplegic arrest. Furthermore, basic science and clinical studies by Buckberg and by our group33,34 showed conclusively that near “ideal” myocardial protection requires infusion of cardioplegia by using simultaneously the antegrade/retrograde routes. It has been shown that each route of administration perfuses different coronary vascular beds. As a result, the current technique of myocardial perfusion during aortic valve surgery is based on simultaneous antegrade and retrograde blood perfusion to ensure proper delivery of oxygenated blood to all coronary vascular beds, avoiding myocardial ischemia. Avoidance of perioperative myocardial ischemic injury could be beneficial in this high-risk group of patients with infective endocarditis, especially when complex procedures are required (double-valve surgery, annular reconstruction, etc.). In these patients, postoperative deterioration of LV function could interact with other clinical variables (such as sepsis, respiratory failure, multiorgan dysfunction, prosthetic valve infection, multivalve involvement, etc.) and increased postoperative morbidity and mortality.
Our study found that survival in patients using the beating-heart approach was comparable to historical series from the literature.1–7,27,28 Operative mortality for infective aortic valve endocarditis remains significant. The combined early and late mortality rate of 42% observed in our patients requiring salvage operations as compared with 18% for those requiring urgent or emergent procedures (Table 4) confirms that surgical outcomes in critically ill patients with multiple comorbid conditions and multisystem organ failure remain poor. It also raises the question as to whether some of these patients requiring salvage procedures should be treated medically and be excluded from surgical intervention, irrespective of the surgical approach used. As suggested by others,35 it is unclear whether some of these salvage patients could be made better surgical candidates had surgical intervention been undertaken earlier. Also, in our series, the surgical mortality for combined aortic and mitral valve operations was higher than that for isolated aortic valve operations (35.7% vs. 12.5%, respectively). The small size of our study precluded statistical analyses to confirm these trends. However, this observation would confirm that, not surprisingly, multiple valve involvement is a risk factor for adverse outcome.36
Although in our small study group we did not observe any survival benefit as compared with previous series from the literature, the beating-heart strategy resulted in improved preservation of LV function, as demonstrated by the preservation of indicators of LV systolic function (Fig. 1). In contrast to previous reports showing deterioration of LV functional parameters following aortic valve surgery,11,12,29 EF and FS remained unchanged in our patients undergoing surgery. Further, we noted a significant decrease in LVEDD after surgery, consistent with the ventricular remodeling process induced by the elimination of aortic insufficiency.
We used biologic and mechanical prostheses, as reported by others,26–28 to reduce the surgical risk associated with more complex procedures involving homograft and autograft replacement. This could be of considerable importance especially in the setting of multivalve endocarditis requiring double-valve surgery or complex reoperations, and in patients with multiple risk factors. The significant number of double-valve operations and redo procedures in our series supports this strategy. With regard to possible contraindications to beating-heart aortic valve surgery, in our experience these include the inability to expose the aortic valve due to the presence of blood in the field, and the inability to provide adequate antegrade/retrograde myocardial perfusion to sustain myocardial energy metabolism at normothermia. Should this occur, the surgeon can deliver cardioplegia to obtain complete electro-mechanical arrest as in conventional aortic valve procedures. This situation was not encountered in this series of patients. With respect to the potential of having blood obscuring the operating field when this strategy of myocardial protection is used, we have not found that exposure and visualization are negatively affected, although some learning curve is involved as compared with conventional cardioplegic techniques. We have used the same technique of perfusion during complex aortic root procedures as well.21 Visualization during complex surgery may be difficult at times, ie, during coronary reimplantation when a root reconstructive procedure is performed. In these cases, one has the option of delivering conventional cardioplegia for a selected portion of the operation (ie, coronary reimplantation), and then resume continuous normothermic perfusion. Overall, although we do not have comparative data to support it, we feel that in these complex procedures the strategy of continuous perfusion extends the period of safe aortic cross-clamping, possibly reducing the risk of myocardial ischemic injury.
We acknowledge that our study has several important limitations. In addition to the small number of patients, we did not compare beating-heart patients with patients receiving conventional cardioplegic techniques. This must be performed before recommending this technique for widespread use. The clinical variables affecting outcomes in patients with endocarditis are numerous. The small sample size precludes a statistical analysis in a heterogeneous patient population where some patients were lost to follow-up and several variables could have affected outcomes (different valve disease processes, age, EF, risk factors, etc.). Additional limitations may involve the potential bias related to echocardiographic estimates of LV function. Our study did not show a survival advantage of the beating-heart approach as compared with historical series in which conventional myocardial protective strategies were used. In fact, it confirmed that surgical mortality for aortic endocarditis remains significant, probably as a result of powerful preoperative risk factors, comorbidities, and multivalve involvement. However, our data also suggest that the beating-heart technique could contribute to preservation of ventricular function in patients with aortic valve endocarditis requiring surgery, as demonstrated by postoperative preservation of key indicators of LV systolic function.
In summary, we, herein, describe an alternative technique of myocardial protection that allows for performance of complex aortic valve procedures without myocardial ischemia. The role that this strategy may have in improving outcomes following aortic valve surgery for endocarditis remains to be investigated.
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This group has pioneered the beating-heart approach to valve surgery. In this article, they document the feasibility of this approach in the difficult group of patients with endocarditis. However, it is important for the reader to understand that this small, retrospective review does not address whether this is a comparable technique to standard, arrested-heart aortic valve surgery. This would require a randomized study, or certainly a much larger experience with longer-term follow-up. For practicing surgeons, the beating-heart approach is a nice technique to have in your armamentarium and can be particularly helpful in rare situations. The technique theoretically avoids myocardial ischemia, but this is only true if one provides continuous substrate infusion—either retrograde or antegrade—during the case.
Keywords:© 2009 Lippincott Williams & Wilkins, Inc.
Aortic valve; Myocardial protection; Beating heart