**4. Type of prosthesis**

Although PVE secondary to candidemia is rare, accounting for 5–10% of all cases, it carries a high mortality rate [28]. In a retrospective study of 44 cases of nosocomial fungemia in patients with prosthetic heart valves by Nasser et al., 9% developed fungal endocarditis at a mean of 232 days after documented candidemia [29]. Hence, patients with candidemia must be treated aggressively in the acute setting and be provided close long-term follow-up.

Implantation of a prosthetic valve in the setting of native valve contamination without known active infection may increase the risk of PVE. For this reason, many surgeons routinely culture excised valve leaflets to ensure that the new valve is not contaminated at the time of implantation. In a study of 222 patients by Campbell et al., 14.4% who underwent elective valve replacement had positive valve cultures [30]. Coagulase-negative *Staphylococcus* was the most common bacterial isolate [30]. None of these patients had clinical evidence of infection. Only 3% of patients with positive valve cultures developed PVE. Most positive native valve cultures were thought to be false positives. Campbell concluded that positive cultures did not

predict PVE and recommended against routinely obtaining native valve cultures [30].

from two or more sites [32]. Several decades later, the issue remains unresolved.

contamination [35].

118 Advanced Concepts in Endocarditis

Nonetheless, the potential morbidity and mortality of PVE may justify the practice of culturing excised valve tissue and treating patients with positive cultures. Intraoperative contamination at the time of valve implantation may occur from a variety of sources. Cardiac surgical procedures are complex and entail numerous intravascular monitoring devices as well as the circuit of the cardiopulmonary bypass machine. This complexity may contribute to the incidence of positive intraoperative blood cultures. In 1969, Ankeney and Parker reported positive intraoperative blood cultures in 19% of patients undergoing open cardiac surgery [31]. In a 1974 study of 66 patients undergoing open cardiac surgery, Kluge et al. reported a 71% incidence of positive intraoperative cultures from at least one site and a 20% incidence

In a 2004 study of 64 patients who underwent cardiovascular surgery, Shindo et al. reported positive intraoperative blood cultures in 16% of patients who underwent cardiopulmonary bypass [33]. Intraoperative blood salvage is routinely used in cardiac surgical procedures to avoid homologous blood transfusion. Autotransfusion is associated with lower risk of hypersensitivity reactions and infections compared to transfusion of homologous blood [33]. However, intraoperative blood salvage is associated with a high incidence of positive cultures. Shindo et al. reported positive blood cultures in 67% of cases using intraoperative blood salvage, excluding cardiopulmonary bypass [33]. In a 1992 study of 31 patients, Bland et al. reported positive cultures in 97% of cases using intraoperative blood salvage [34]. In a 1999 study of 10 patients by Reents et al., 90% of cases using a cell-saving device had bacterial

Hemodialysis has also been associated with endocarditis, particularly with the increasing prevalence of dialysis dependence. In a study of 329 patients with endocarditis by Cabell et al., 20.4% were hemodialysis dependent [36]. Hemodialysis was independently associated with the development of *Staphylococcus aureus* endocarditis. The frequency of hemodialysis dependence also significantly increased during the 7-year study period, from 6.7 to 21% [36]. There was a corresponding significant increase in *Staphylococcus aureus* endocarditis during The incidence of PVE in mechanical and bioprosthetic valves is comparable [39]. Patients with mechanical prostheses have a higher risk of PVE in the first 3 months following valve replacement than those with bioprostheses [19]. The reason for higher risk of PVE in the early postoperative period with mechanical prostheses is unclear. Allografts lack prosthetic material and have a very low incidence of PVE in the early postoperative period. This suggests that mechanical prostheses have a tendency to develop early PVE, attributed to surface contamination at the time of surgery [19].

PVE in mechanical and bioprosthetic valves differs in anatomic involvement [40]. Infection of mechanical valves involves the junction between the sewing ring and annulus. This leads to the development of perivalvular abscesses, valve dehiscence, pseudoaneurysms, and fistulas. In comparison, infection of bioprosthetic valves is localized to the leaflets, leading to vegetations, cusp rupture, and perforation [40]. Endocarditis after mitral valve repair is rare. In a study of 30 patients, Gillinov et al. reported only 3% of cases of failed mitral valve repair as being caused by endocarditis [41]. In a study of 1275 mitral valve repairs over a 9-year period, Karavas et al. reported a 0.7% incidence of mitral valve endocarditis requiring surgical intervention [42]. The reason for this low incidence is likely related to less prosthetic material for potential infection with mitral valve repair than replacement.

#### **4.1. Aortic valve prosthetic valve endocarditis**

Aortic PVE is associated with substantial early morbidity and mortality. Regardless of the type of infected valve, mechanical or bioprosthetic, extensive tissue destruction may complicate aortic PVE. In a 20-year study of surgical treatment of aortic PVE by Perrotta et al., perivalvular abscess was reported in 83% of patients [43]. Comparably, Sabik et al. reported a 78% abscess rate in 103 patients with aortic PVE [44]. Abscess formation may be complicated by pseudoaneurysm and fistulisation [40]. Complete aortoventricular discontinuity has been reported in 40% of patients with aortic PVE [44]. Medical therapy alone has been associated with mortality rates as high as 70%, improved to 4–20% with surgical intervention. Significant risk factors for mortality include older age, higher preoperative creatinine, shorter interval from initial valve operation to reoperation for PVE, and fistula development. Mortality results from sepsis and multiple organ failure [44].

Aortic PVE is characterized by varying degrees of annular involvement. Extension of infection into the annular and periannular structures is a major determinant of both early and late surgical outcomes. The extent of valvular destruction relates to the virulence of the infecting organism and the duration of infection [45]. The inflammatory process of aortic PVE begins at the prosthetic sewing ring and extends through the aortic annulus, commonly in the region of aortomitral continuity [46]. The spectrum of periannular infection ranges from simple localized abscess to larger subannular aneurysm, with or without perforation into adjacent cardiac chambers. Progressive periannular infection may disrupt aortoventricular continuity or the aortomitral trigone, leading to intracardiac fistulae [44].

low operative mortality, but limited durability due to progressive dilation of the autograft root causing severe aortic valve regurgitation [53]. The Ross procedure is typically performed

Prosthetic Valve Endocarditis

121

http://dx.doi.org/10.5772/intechopen.79758

Morbidity and mortality associated with allograft aortic root replacement in the setting of PVE with involvement of the periannular region is significant [54]. A retrospective study of 32 patients with complicated aortic PVE who underwent allograft aortic root replacement by Dossche et al. reported annular abscess in 81%, aortomitral discontinuity in 43%, and aortoventricular discontinuity in 34%. There was a 9.4% operative mortality rate in this study, attributed to multiple organ failure and low cardiac output. The reported 5-year survival rate was 97.3%, and 5-year freedom from recurrent endocarditis was 96.5% [54]. As described, Sabik et al. reported similar rates of periannular abscess and aortoventricular discontinuity at 78 and 40%, respectively [44]. Reconstruction with cryopreserved allograft was associated with an in-hospital mortality rate of 3.9% in this study. Long-term survival rates at 1, 2, 5, and 10 years were 90, 86, 73, and 56%, respectively. Only 3.9% of patients required reoperation for

Despite the advantages provided by allografts in the treatment of aortic PVE, their availability is limited. This has led to the use of mechanical valve-conduits for aortic root reconstruction with excellent results in the treatment of aortic PVE. Hagl et al. reported favorable results in a retrospective study of 28 patients who underwent aortic root replacement for PVE using prosthetic material rather than homograft [55]. Reported in-hospital mortality was 11%, and

A study of 127 patients by Avierinos et al. compared the treatment of aortic endocarditis with aortic homograft in 43% and with conventional prosthesis in 57% [56]. In-hospital mortality was comparable between homograft and prosthesis at 11 and 8%, respectively. Prosthetic valve endocarditis was the only variable independently associated with in-hospital mortality. This mortality rate was not influenced by the type of valvular substitute, even in cases of annular abscess. There was no significant difference in endocarditis recurrence, prosthesis dysfunction, or cardiovascular mortality between aortic homograft and prosthesis at

Aortic root replacement with stentless porcine xenografts has been developed as a surgical alternative in aortic PVE [57]. The stentless valve provides flexibility in reconstruction of the debrided myocardium. However, it places prosthetic material in the infected area, risking infection of the prosthetic valve-conduit. A study of 132 patients who underwent aortic root replacement with stentless porcine xenografts by LeMaire et al. reported a 7.6% mortality rate. There was a 6.8% incidence of late valve-related complications, including prosthetic endocarditis and annular pseudoaneurysm [57]. Reconstruction with cryopreserved allograft

In addition to the difficulty associated with extensive resection of the prosthetic valveconduit and surrounding tissue, two particular challenges must be overcome to replace the infected valve-conduit. The first challenge is reimplantation of the coronary artery ostia into the allograft. Scarring from the initial procedure may make it difficult to effectively mobilize

the incidence of recurrent endocarditis requiring reoperation was only 4% [55].

in critically ill patients and is used very selectively in PVE.

recurrent PVE; 95% were free of recurrent PVE at 2 years [44].

10 years [56].

remains the preferred surgical strategy.

The goals of surgical intervention for aortic PVE include [44]:


Reconstruction is complicated by severe destruction of the aortic root seen in PVE, characterized by development of abscesses, fistulas, aortoventricular discontinuity, and ventricular septal defects [47]. Achievement of the goals of surgical intervention for aortic PVE may require radical cardiac debridement. Failure to adhere to these principles poses significant risk for recurrent infection and valve dehiscence.

Following complete debridement, appropriate surgical reconstruction is guided by specific circumstances. In the majority of cases, an aortic root replacement is indicated [48]. A tensionfree repair, excluding attenuated areas from high pressures, is essential [48]. If necessary, transmural sutures may be used to secure the conduit to the interventricular crest. Surgical principles dictate minimal use of synthetic material in the infected area. Aortic homograft is considered the replacement valve-conduit of choice in the treatment of aortic PVE [49]. Homograft vascular tissue is significantly more resistant to infection than prosthetic material. Aortic root replacement with homograft minimizes prosthetic material in the area of infection, thereby reducing risk of recurrent infection. The incidence of reinfection is low, ranging from 0 to 6.8% [49].

The use of allograft provides greater flexibility in the reconstruction of debrided areas [50]. Implantation may exclude abscess cavities from circulation by sewing the proximal anastomosis of the allograft to the inferior border of the abscess cavity [50]. Use of an aortic homograft with its attached mitral leaflet is particularly valuable in this regard [51].

The Ross operation, using pulmonary allograft, has been proposed as an alternative surgical option for the treatment of complex aortic PVE [51]. An initial study in 1994 by Joyce et al. of pulmonary allograft replacement reported success in six patients between 10 and 32 years of age with aortic valve endocarditis, with no mortality or reinfection [52]. In 2002, a retrospective study of 343 patients who underwent the Ross procedure by Takkenberg et al. reported low operative mortality, but limited durability due to progressive dilation of the autograft root causing severe aortic valve regurgitation [53]. The Ross procedure is typically performed in critically ill patients and is used very selectively in PVE.

Aortic PVE is characterized by varying degrees of annular involvement. Extension of infection into the annular and periannular structures is a major determinant of both early and late surgical outcomes. The extent of valvular destruction relates to the virulence of the infecting organism and the duration of infection [45]. The inflammatory process of aortic PVE begins at the prosthetic sewing ring and extends through the aortic annulus, commonly in the region of aortomitral continuity [46]. The spectrum of periannular infection ranges from simple localized abscess to larger subannular aneurysm, with or without perforation into adjacent cardiac chambers. Progressive periannular infection may disrupt aortoventricular continuity or the

Reconstruction is complicated by severe destruction of the aortic root seen in PVE, characterized by development of abscesses, fistulas, aortoventricular discontinuity, and ventricular septal defects [47]. Achievement of the goals of surgical intervention for aortic PVE may require radical cardiac debridement. Failure to adhere to these principles poses significant

Following complete debridement, appropriate surgical reconstruction is guided by specific circumstances. In the majority of cases, an aortic root replacement is indicated [48]. A tensionfree repair, excluding attenuated areas from high pressures, is essential [48]. If necessary, transmural sutures may be used to secure the conduit to the interventricular crest. Surgical principles dictate minimal use of synthetic material in the infected area. Aortic homograft is considered the replacement valve-conduit of choice in the treatment of aortic PVE [49]. Homograft vascular tissue is significantly more resistant to infection than prosthetic material. Aortic root replacement with homograft minimizes prosthetic material in the area of infection, thereby reducing risk of recurrent infection. The incidence of reinfection is low, ranging

The use of allograft provides greater flexibility in the reconstruction of debrided areas [50]. Implantation may exclude abscess cavities from circulation by sewing the proximal anastomosis of the allograft to the inferior border of the abscess cavity [50]. Use of an aortic homo-

The Ross operation, using pulmonary allograft, has been proposed as an alternative surgical option for the treatment of complex aortic PVE [51]. An initial study in 1994 by Joyce et al. of pulmonary allograft replacement reported success in six patients between 10 and 32 years of age with aortic valve endocarditis, with no mortality or reinfection [52]. In 2002, a retrospective study of 343 patients who underwent the Ross procedure by Takkenberg et al. reported

graft with its attached mitral leaflet is particularly valuable in this regard [51].

aortomitral trigone, leading to intracardiac fistulae [44].

The goals of surgical intervention for aortic PVE include [44]:

**1.** complete debridement of infected and nonviable tissue,

**2.** repair of associated cardiac defects, **3.** reconstruction of the aortic root, and

120 Advanced Concepts in Endocarditis

**4.** placement of a competent valve.

from 0 to 6.8% [49].

risk for recurrent infection and valve dehiscence.

Morbidity and mortality associated with allograft aortic root replacement in the setting of PVE with involvement of the periannular region is significant [54]. A retrospective study of 32 patients with complicated aortic PVE who underwent allograft aortic root replacement by Dossche et al. reported annular abscess in 81%, aortomitral discontinuity in 43%, and aortoventricular discontinuity in 34%. There was a 9.4% operative mortality rate in this study, attributed to multiple organ failure and low cardiac output. The reported 5-year survival rate was 97.3%, and 5-year freedom from recurrent endocarditis was 96.5% [54]. As described, Sabik et al. reported similar rates of periannular abscess and aortoventricular discontinuity at 78 and 40%, respectively [44]. Reconstruction with cryopreserved allograft was associated with an in-hospital mortality rate of 3.9% in this study. Long-term survival rates at 1, 2, 5, and 10 years were 90, 86, 73, and 56%, respectively. Only 3.9% of patients required reoperation for recurrent PVE; 95% were free of recurrent PVE at 2 years [44].

Despite the advantages provided by allografts in the treatment of aortic PVE, their availability is limited. This has led to the use of mechanical valve-conduits for aortic root reconstruction with excellent results in the treatment of aortic PVE. Hagl et al. reported favorable results in a retrospective study of 28 patients who underwent aortic root replacement for PVE using prosthetic material rather than homograft [55]. Reported in-hospital mortality was 11%, and the incidence of recurrent endocarditis requiring reoperation was only 4% [55].

A study of 127 patients by Avierinos et al. compared the treatment of aortic endocarditis with aortic homograft in 43% and with conventional prosthesis in 57% [56]. In-hospital mortality was comparable between homograft and prosthesis at 11 and 8%, respectively. Prosthetic valve endocarditis was the only variable independently associated with in-hospital mortality. This mortality rate was not influenced by the type of valvular substitute, even in cases of annular abscess. There was no significant difference in endocarditis recurrence, prosthesis dysfunction, or cardiovascular mortality between aortic homograft and prosthesis at 10 years [56].

Aortic root replacement with stentless porcine xenografts has been developed as a surgical alternative in aortic PVE [57]. The stentless valve provides flexibility in reconstruction of the debrided myocardium. However, it places prosthetic material in the infected area, risking infection of the prosthetic valve-conduit. A study of 132 patients who underwent aortic root replacement with stentless porcine xenografts by LeMaire et al. reported a 7.6% mortality rate. There was a 6.8% incidence of late valve-related complications, including prosthetic endocarditis and annular pseudoaneurysm [57]. Reconstruction with cryopreserved allograft remains the preferred surgical strategy.

In addition to the difficulty associated with extensive resection of the prosthetic valveconduit and surrounding tissue, two particular challenges must be overcome to replace the infected valve-conduit. The first challenge is reimplantation of the coronary artery ostia into the allograft. Scarring from the initial procedure may make it difficult to effectively mobilize the left and right main coronary ostia for anastomosis to the allograft without undue tension. Raanani et al. described surgical reconstruction of the left main coronary artery using an autologous pericardial or saphenous vein patch [58]. The second challenge is achieving adequate resection and debridement of the distal graft-to-aorta anastomosis, which may require deep hypothermia and circulatory arrest. Furthermore, an allograft may not have sufficient length to reach the distal aortic anastomosis. Sabik et al. described the use of a second allograft to bridge the distance between the first allograft and the aorta [44].

**5. Operations with recent stroke**

aortic endocarditis [66].

**6. Indications for surgery**

**1.** *Indications for surgery.*<sup>1</sup>

(Class IIa).

endocarditis [68].

1

microorganisms (Class I).

• Relapsing infection (Class IIa).

Neurologic sequelae occur in 25–70% of cases of infective endocarditis and portend increased mortality [64]. The mechanisms of neurologic injury include ischemic infarction secondary to embolization, hemorrhagic transformation of ischemic infarction, pyogenic arteritis, and rupture of intracranial mycotic aneurysm [65]. Systemic embolization occurs in 12.9% of patients with left-sided endocarditis after initiation of antibiotic therapy [66]. Of those with embolic events, 52% affect the central nervous system, and 65% occur within 2 weeks of initiation of antibiotic therapy [66]. Risk factors for embolization include vegetation size and mobility [66, 67]. There is no significant difference in incidence of embolization between native and prosthetic valve endocarditis. The risk of embolization is higher in mitral endocarditis than in

Prosthetic Valve Endocarditis

123

http://dx.doi.org/10.5772/intechopen.79758

The most common neurologic complication is ischemic stroke [65]. From a surgical perspective, the primary concern is hemorrhagic transformation of an ischemic infarct as a consequence of anticoagulation required during cardiopulmonary bypass [65]. Asymptomatic cerebral infarctions may occur in 30–40% of patients with endocarditis [64]. For this reason, it may be advisable to exclude an ischemic stroke with preoperative computed tomography. Clinically, silent or small infarcts should not delay cardiac surgery, since the risk of progression is low [64]. However, with the evidence of larger infarcts or intracerebral hemorrhage, surgical intervention should be delayed up to 4 weeks due to the associated risk of a significant neurologic event during cardiopulmonary bypass [64]. In such patients, the need for

While there are a variety of resources available to assist in the decision making regarding interventions for prosthetic valve endocarditis, the key principles of therapy have been advo-

• Left-sided infectious endocarditis caused by S. aureus, fungal, or other highly resistant

• Recurrent emboli and persistent vegetations despite appropriate antibiotic therapy

Adapted from The American Association of Thoracic Surgeons consensus statement on the management of infectious

valve replacement should be balanced with high perioperative neurologic risk.

• Valve dysfunction resulting in symptoms of heart failure (Class I).

cated by both American [68, 69] and European societies [70].

High operative mortality rates have been reported for the replacement of infected valve-conduits, attributed to the degree of surgical difficulty. In a study of 11 patients with infected ascending aortic grafts who underwent composite valve graft placement by LeMaire and Coselli in 2007, a 30-day mortality rate of 46% was reported [59]. In comparison, a study of 12 patients who underwent composite replacement of the aortic valve and ascending aorta for infective endocarditis by Ralph-Edwards et al. reported an operative survival rate of 91.7% [60]. In this series, extensive debridement was performed, often requiring resection of the infected portion of the left ventricular outflow tract with circumferential reconstruction using bovine pericardium. It was often necessary to extend the length of the coronary arteries with saphenous vein or expanded polytetrafluoroethylene grafts to facilitate reimplantation as well [60]. As described, in a study of 23 patients who underwent ascending aorta and aortic valve replacement with the prosthetic material for acute PVE, Hagl et al. reported an 11% in-hospital mortality rate and a 4% incidence of recurrent endocarditis requiring reoperation at 4 months [55].

#### **4.2. Mitral prosthetic valve endocarditis**

Endocarditis is rare after mitral valve repair. The rate of freedom from endocarditis at 10 years following mitral valve repair is estimated at 95–99% [61]. Although native valve endocarditis can often be managed medically, PVE typically requires early operation. In a study of 22 patients with endocarditis after mitral valve repair by Gillinov et al., 68.1% underwent repeat mitral valve operations. Mitral valve replacement was required in 73.3%, and rerepair was performed in 26.7%. Following reoperation, 30-day, 1-year, and 5-year rates of freedom from reoperation were 65, 41, and 26%, respectively [61]. The principles of surgical management include the removal of all infected and devitalized tissue as well as the removal of the annuloplasty ring. If rerepair is not possible, replacement is necessary. Destruction of the mitral annular region is less common than periaortic annular destruction. Surgical debridement and resection of abscess formation in the posterior mitral annulus or in the region of aortomitral continuity is a significant surgical challenge, associated with a high operative mortality.

The mitral annulus may be reconstructed with autologous pericardium after debridement, as described by David and Feindel [62]. If the posterior mitral annular region requires reconstruction, this may be done with pericardium as well [15]. If necessary, the new mitral prosthesis may be translocated onto either the atrial or ventricular side of the annulus. If technically feasible, ventricular translocation may prevent exposure of the attenuated area to high pressure [15]. Aortomitral discontinuity is uncommon and particularly difficult to reconstruct. This trigonal region may be reconstructed using a modification of the technique described by Rastan et al. [63].
