Abstract
Objective
Prosthetic pulmonary valve endocarditis (PPVE) limits survival and quality of life in patients with repaired congenital heart disease. We describe patient outcomes with PPVE in a single center and the application of transcatheter pulmonary valve replacement (TPVR).
Methods
We performed a single-center retrospective review of patients with PPVE from 2010 to 2022. Subjects were stratified by initial treatment: group 1 comprised surgical pulmonary valve replacement (SPVR), group 2 comprised TPVR, and group 3 comprised initial medical therapy without plans for upfront surgical or procedural intervention. Micro-organism data, posttreatment morbidity, length of stay, recurrence, and mortality are reported.
Results
Seventy patients met inclusion criteria; 7% (group 2) underwent TPVR, and 80% of these patients underwent TPVR as a bridge to SPVR. No patients from group 2 had recurrence. Mortality was similar in the upfront SPVR and TPVR groups (group 1: 17.4%, group 2: 20%, group 3: 2.4%). In total, 71% of patients in group 3 eventually required elective SPVR or TPVR, with 25% of patients undergoing TPVR after clearance of blood cultures having recurrence compared with 7.1% of patients who underwent SPVR after clearance of blood cultures.
Conclusions
TPVR is a viable bridge to SPVR in select patients with PPVE and may serve as destination therapy. Recurrence may be more common in patients requiring PVR after clearance of infection. Prospective studies of first-line TPVR as a strategy for bridge-to-surgery in select high risk patients and destination therapy in patients with resolution of bacteremia are needed to define treatment pathways.
Key Words: endocarditis, transcatheter pulmonary valve replacement, prosthetic pulmonary valve endocarditis
PPVE treatment may include initial SPVR, TPVR, or medical therapy.
Central Message.
Transcatheter pulmonary valve replacement may offer a safe bridge or alternative to urgent surgery for high-risk patients with prosthetic pulmonary valve endocarditis.
Perspective.
Prosthetic pulmonary valve endocarditis imposes significant risk and is increasingly common in an aging population with repaired congenital heart disease. Unstable patients have significant morbidity and mortality with emergent surgery. Herein we describe a strategy incorporating transcatheter pulmonary valve replacement for end-organ and right ventricular rehabilitation in select patients.
See Commentary on page XXX.
Infective endocarditis (IE) is a potentially life-threatening condition that is increasingly common in patients with repaired congenital heart disease (140× more prevalent than those without) that may be furthered complicated by multiple previous operations, concomitant congenital cardiac pathology, multidrug-resistant organisms, and implanted prosthetic materials.1 PPVE occurs in 4.8% of patients with congenital heart disease and previous pulmonary valve replacement (PVR) and carries a 7% mortality rate at 3 years.2,3 Prosthetic pulmonary valve endocarditis (PPVE) frequently requires repeated surgical pulmonary valve replacement (SPVR) in an already high-risk patient population, yet the advent of transcatheter pulmonary valve replacement (TPVR) has provided a reliable solution for appropriately selected patients. Although TPVR as an index procedure has been shown to impart a greater risk of IE when compared with SPVR, the role of TPVR in the treatment of PPVE remains undefined.2
Although SPVR is the standard treatment for PPVE, a certain subset of high-risk patients with PPVE present with potentially reversible factors such as acute right ventricular (RV) dysfunction, end-organ injury, and profound metabolic derangements that significantly increase morbidity and imposed mortality with emergent surgical intervention. TPVR offers a potential alternative to early, emergent SPVR in high-risk patients to lessen RV pressures and support cardiac output, end-organ perfusion, and rehabilitation, particularly as a bridge to SPVR while on targeted antibiotic therapy. Although the literature supports consideration of this strategy, there are perceived risks such as recurrent infection, single-center experiences remain limited, and patient selection factors for consideration are undefined. The purpose of this study was to describe our single-center experience with TPVR as a bridge to surgical intervention in select high-risk patients and the rate of conversion to surgical or procedural intervention in medically managed patients.
Methods
A retrospective review was performed of patients with a diagnosis of PPVE after previous PVR at a single, high-volume center from 2010 to 2022. Inclusion criteria included all patients at presentation with PPVE after PVR from 2010 to 2022 with at least 1 year of in-person follow-up. Exclusion criteria included any patients lost to follow-up before 1 year or those without available documentation of the reported outcomes listed to follow. Subjects were stratified according to initial treatment into 3 groups: group 1 comprised initial medical therapy with planned upfront SPVR, group 2 comprised initial medical therapy with planned upfront TPVR, and group 3 comprised those who received a trial of medical therapy without an upfront plan for procedural or surgical intervention. TPVR was chosen as the initial strategy for patients with RV dysfunction, medical instability (defined as requirement for vasoactive and inotrope therapy), and/or end-organ dysfunction. Patients undergoing initial TPVR were determined by our multidisciplinary team to be at exceptionally high or exclusionary risk for SPVR as a result of a combination of the aforementioned factors. All initial congenital heart disease diagnoses and index procedures are included in Table 1.
Table 1.
Patient diagnoses and index procedures
| Patient demographics | Total (n = 70) |
|---|---|
| Sex, M:F | 39 (56%):31 (44%) |
| Cardiac diagnosis | |
| Tetralogy of Fallot | 20 (29%) |
| Truncus arteriosus | 16 (23%) |
| Pulmonary atresia | 7 (10%) |
| Double-outlet right ventricle | 7 (10%) |
| Congenital aortic stenosis | 6 (9%) |
| Congenital pulmonary stenosis | 4 (6%) |
| Dextro-transposition of the great arteries | 3 (4%) |
| Congenitally corrected transposition of the great arteries with pulmonary stenosis | 2 (3%) |
| Pulmonary atresia | 1 (1%) |
| Other | 4 (6%) |
| Initial surgery | |
| Ross procedure | 2 (3%) |
| Truncus arteriosus repair | 16 (24%) |
| Modified Blalock-Thomas-Taussig shunt with/without pulmonary arterioplasty | 14 (19%) |
| Tetralogy repair | 14 (19%) |
| Aortopulmonary window | 1 (1%) |
| Right ventricle-to-pulmonary artery conduit | 4 (5%) |
| Coarctation repair with/without subaortic relief | 2 (3%) |
| Balloon aortic valvuloplasty | 6 (8%) |
| Balloon pulmonary valvuloplasty | 4 (5%) |
| Central shunt | 1 (1%) |
| Damus-Kaye-Stanzel | 1 (1%) |
| Double-switch procedure | 1 (1%) |
| Arterial switch | 3 (4%) |
| Rastelli procedure | 1 (1%) |
| Right ventricular outflow tract stent | 1 (1%) |
| Subaortic/supra-aortic stenosis relief | 1 (1%) |
Initial diagnoses and index procedures of all included patients are shown. M, Male; F, female.
Sex, number of previous pulmonary valve (PV) interventions, age at diagnosis, causative organism, RV dysfunction severity, mortality rates, and morbidities including intensive care unit length of stay (LOS) in days, hospital LOS in days, new renal-replacement therapy requirement, extracorporeal membrane oxygenation requirement, mechanical circulatory support duration, relapse, recurrence, and new diagnoses of acute kidney injury, liver dysfunction, pulmonary embolism, neurologic events, and peripheral embolism were obtained from the medical record and listed for each group. Given the small sample size, no direct statistical comparisons were made. All data were acquired and used under approval from the Colorado Multiple Institutional Review Board at the University of Colorado – Denver, Anschutz Medical Campus approval number 24-0313 and date of approval February 21, 2024.
Results
In total, 88 patients were identified, and 70 had sufficient data for inclusion (group 1: n = 23, group 2: n = 5, group 3: n = 42). Initial diagnoses and index procedures of patients are listed in Table 1. As shown in Table 2, patients in group 1 underwent surgical intervention at a median time of 13 days from admission (7-49 days). Patients in group 2 underwent percutaneous intervention at a median time of 12 days from admission (7-16 days). Four of 5 patients (80%) in group 2 underwent initial TPVR as a bridge to SPVR. Mortality in the TPVR group was similar to the upfront SPVR group (group 1: 17.4%, group 2: 20%, group 3: 2.4%). One patient (20%) required extracorporeal membrane oxygenation for 5 days in the TPVR group, whereas 2 patients in group 1 (9%) required mechanical circulatory support for a median of 1 day. No patients in group 2 had relapse/recurrence during the follow-up period. LOS was greatest in group 1 (group 1: 15 days, group 2: 11 days, and group 3: 6 days).
Table 2.
Patient characteristics and outcomes
| Patient variable | Total (n = 70) | Group 1 (surgical) (n = 23) | Group 2 (percutaneous) (n = 5) | Group 3 (conservative) (n = 42) |
|---|---|---|---|---|
| Sex, M:F | 39:31 | 12:11 | 3:2 | 24:18 |
| Number of previous PV interventions | ||||
| <3 | 46 (66%) | 12 (52%) | 3 (60%) | 30 (71%) |
| ≥3 | 24 (34%) | 11 (48%) | 2 (40%) | 11 (26%) |
| Age at IE diagnosis, mo | 205 (139-295) | 200 (101-255) | 248 (245-274) | 198 (145-338) |
| Organism | ||||
| Streptococcus mitis | 14 (20%) | 5 (22%) | – | 9 (21%) |
| Streptococcus Viridans | 2 (3%) | 1 (4%) | – | 1 (2%) |
| MSSA | 22 (31%) | 10 (14%) | 2 (40%) | 19 (45%) |
| Enterococcus | 5 (7%) | 1 (1%) | – | 4 (10%) |
| Culture negative | 6 (9%) | 2 (3%) | – | 4 (10%) |
| Other | 21 (30%) | 4 (6%) | 3 (60%) | 14 (20%) |
| RV dysfunction at admission | ||||
| Mild | 23 (34%) | 9 (39%) | 1 (20%) | 13 (31%) |
| Moderate | 6 (9%) | 1 (17%) | 2 (40%) | 3 (7%) |
| Severe | 6 (9%) | 2 (9%) | – | 3 (7%) |
| Mortality | 6 (9%) | 4 (17%) | 1 (20%) | 1 (2%) |
| Morbidity | ||||
| ICU LOS, d | 2 (1-5) | 2 (1-5) | 3 (1-5) | 2 (1-3) |
| Hospital LOS, d | 7 (6-15) | 15 (8-19) | 11 (7-22) | 6 (4-8) |
| AKI | 17 (24%) | 5 (22%) | 3 (60%) | 9 (21%) |
| AKI requiring RRT | 1 (1%) | 1 (4%) | – | – |
| Liver dysfunction | 12 (17%) | 3 (13%) | 3 (60%) | 6 (14%) |
| Pulmonary embolism | 13 (19%) | 6 (26%) | 1 (20%) | 6 (14%) |
| Neurologic event | 2 (3%) | 1 (4%) | – | 1 (2%) |
| Peripheral embolism | 3 (4%) | 2 (9%) | – | 1 (2%) |
| ECMO | 3 (4%) | 2 (9%) | 1 (20%) | 6 (14%) |
| Time on MCS, d | 2 (1-5) | 1 | 5 | – |
| Relapse | 3 (4%) | 1 (4%) | – | 2 (5%) |
| Recurrence | 8 (11%) | 2 (9%) | – | 6 (14%) |
Outcomes of prosthetic pulmonary valve endocarditis treatment stratified by treatment pathway. Group 1: surgical pulmonary valve replacement, group 2: transcatheter pulmonary valve replacement, group 3: medical therapy. M, Male; F, female; PV, pulmonary valve; IE, infective endocarditis; MSSA, methicillin-sensitive Staphylococcus aureus; RV, right ventricular; ICU, intensive care unit; LOS, length of stay; AKI, acute kidney injury; RRT, renal-replacement therapy; ECMO, extracorporeal membrane oxygenation; MCS, mechanical circulatory support.
Patients in group 3 were initially managed medically with antibiotics only. From group 3, 14 patients (33%) underwent semielective surgical intervention at a median of 42 days (17-147 days) after antibiotic initiation and clearance of blood cultures. Still others with clearance of infection (n = 16, 67%) underwent TPVR at a median of 624 days (225-1667 days). All patients from group 3 who underwent TPVR after successful clearance of infection defined by negative blood culture results, and all patients who underwent SPVR after initial medical management were living at the end of the study period. However, 4 of the 16 (25%) patients in group 3 undergoing TPVR after clearance of cultures and 1 of the 14 (7%) patients in group 3 undergoing SPVR after clearance of cultures experienced recurrence. Methicillin-sensitive Staphylococcus aureus (MSSA) was the most common microorganism identified (n = 22, 31%), necessitating early surgery at a median of 12 days from diagnosis (6-15 days).
Discussion
TPVR outcomes including mortality, freedom from reintervention, and incidence of pulmonary regurgitation have supported adoption of this treatment strategy in patients with congenital heart disease as a less-invasive and durable alternative to SPVR in appropriately selected patients. With advantages in hospital LOS and the avoidance of multiple sternotomies, the evolution of this treatment strategy has been a welcomed addition to the treatment armamentarium of congenital heart surgical and interventional teams.4, 5, 6 Although TPVR is a well-established treatment strategy for noninfectious prosthetic pulmonary valve stenosis and insufficiency, its adoption in patients with endocarditis remains undefined. Accepting that the incidence of IE remains greater after TPVR when compared with SPVR as an index procedure, the importance of multidisciplinary decision-making in candidate and technique selection cannot be understated.4, 5, 6, 7 Building upon experiences with transcatheter aortic valve replacement in patients treated with antibiotic therapy for IE, our group sought to apply similar considerations to selectively applying TPVR as a rehabilitation strategy before definitive surgical repair. Transcatheter treatment strategies in the treatment of endocarditis carry most notably the potential for recurrent infection and have a demonstrably greater incidence of both recurrent heart failure and valvular insufficiency.8 With these considerations, surgical valve replacement has remained the recommended standard across multidisciplinary guidelines for refractory endocarditis. Thus, the purpose of this study was not to propose TPVR as a superior strategy to SPVR but to provide a multidisciplinary decision-making alternative to first-line SPVR in select high-risk patients while also providing a comprehensive report of our experience with SPVR and TPVR in a complex and diverse patient population.
The adoption of TPVR as a bridge-to-surgery in patients with congenital heart disease and PPVE evolved within a cohort of patients who were deemed at exceedingly high risk for surgical intervention secondary to most notably, RV dysfunction, multiple previous operations with high-risk sternal reentry, end-organ dysfunction, and thrombocytopenia. Notably, within the reported series, survival was comparable in patients who underwent initial TPVR (80%) compared with primary surgery (82.6%) in the setting of PPVE. Further, LOS was significantly lower in patients who underwent TPVR at initial presentation compared with the early surgery group, reflecting the surgical risk often accepted with operative treatment at the height of the infectious disease burden when end-organ and RV function may be compromised. Our experience supports the select use of early TPVR as a strategy to bridge to definitive surgical intervention in patients who are poor surgical candidates at initial presentation with PPVE. Importantly, we were able to achieve improved RV and end-organ function in well-selected patients and potentially avoided the risks associated with first-line surgery. Prospective, multidisciplinary studies are needed to further support this treatment strategy while also determining which patients may be considered for TPVR as destination therapy after the clearance of blood cultures following medical management. In this small series, 25% of patients undergoing TPVR after the resolution of bacteremia had recurrence compared with 7.1% of patients undergoing SPVR after the clearance of blood cultures. Larger studies are needed to determine whether recurrence is significantly more likely in patients who undergo TPVR after being managed medically initially. It additionally remains undefined whether patients with specific disease features and organism susceptibilities may be candidates for early TPVR as definitive therapy. Miranda and colleagues9 reported that 35% of adult patients with PPVE can be managed without SPVR.9 In the present study, 60% of patients were initially managed with antibiotic therapy alone. Although 83% of patients eventually underwent SPVR or TPVR, many patients underwent replacement at greater than 4 years after the initial presentation. Consistent with current literature, the most commonly identified organism was MSSA. Within our cohort, MSSA predominance supported earlier surgery, given the potential for biofilm development that may reduce efficacy of antibiotic in sterilization.
We acknowledge the limitations of this study in the inherent selection bias that may be present in our multidisciplinary algorithm for care and retrospective review of outcomes, the presented data support consideration of TPVR as a bridge to surgery in high-risk patients presenting with PPVE. As described by Orzech and colleagues,10 biological prosthetic valve and previous cardiac surgery are among the determinant factors for recurrent valve endocarditis; therefore, surgical or procedural intervention should be preferred to medical treatment after a first episode of PPVE. Further research is therefore warranted to define anatomic, microbiologic, and systemic factors that may support TPVR either as definitive therapy or as a bridge to surgery.
Conclusions
Surgical treatment remains the standard of care for complicated, advanced PPVE, yet early surgical intervention carries significant morbidity and mortality associated with the systemic factors often associated with advanced disease. In high-risk candidates for immediate surgical intervention (presence of multiorgan dysfunction, neurologic sequalae precluding cardiopulmonary bypass, thrombocytopenia, and severe RV dysfunction), our experience supports selective use of TPVR as a bridge to definitive surgery after rehabilitation and relief of imposed RV afterload. In addition to defining which patients may benefit from TPVR as a bridge-to-surgery, further research should consider whether TPVR may serve as destination therapy in select patients of exclusionary surgical risk and/or favorable microbiologic profiles. Multidisciplinary evaluation incorporating interventionalists, surgeons, critical care physicians, and infectious disease experts is central to the success of this decision-making algorithm to achieve optimal outcomes.
Conflict of Interest Statement
The authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Footnotes
This work was funded and made possible by the support of the Meg F. Rady and Family Chair in Congenital Cardiac Surgery at the University of Colorado School of Medicine and the University of Colorado School of Medicine StARR Program Award, National Heart, Lung, and Blood Institute grant R38 HL143511.
Drs Ruiz Solano and Breithaupt are co-first authors.
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