Isolated mitral valve endocarditis: Patient, disease, and surgical factors that influence outcomes.

OBJECTIVE: The objectives of this study were to investigate patient characteristics, valve pathology, bacteriology, and surgical techniques related to outcome of patients who underwent surgery for isolated native (NVE) or prosthetic (PVE) mitral valve endocarditis. METHODS: From January 2002 to January 2020, 447 isolated mitral endocarditis operations were performed, 326 for NVE and 121 for PVE. Multivariable analysis of time-related outcomes used random forest machine learning. RESULTS: Staphylococcus aureus was the most common causative organism. Of 326 patients with NVE, 88 (27%) underwent standard mitral valve repair, 43 (13%) extended repair, and 195 (60%) valve replacement. Compared with NVE with standard repair, patients who underwent all other operations were older, had more comorbidities, worse cardiac function, and more invasive disease. Hospital mortality was 3.8% (n = 17); 0 (0%) after standard valve repair, 3 (7.0%) after extended repair, 8 (4.1%) after NVE replacement, and 6 (5.0%) after PVE re-replacement. Survival at 1, 5, and 10 years was 91%, 75%, and 62% after any repair and 86%, 62%, and 44% after replacement, respectively. The most important risk factor for mortality was renal failure. Risk-adjusted outcomes, including survival, were similar in all groups. Unadjusted extended repair outcomes, particularly early, were similar or worse than replacement in terms of reinfection, reintervention, regurgitation, gradient, and survival. CONCLUSIONS: A patient- and pathology-tailored approach to surgery for isolated mitral valve endocarditis has low mortality and excellent results. Apparent superiority of standard valve repair is related to patient characteristics and pathology. Renal failure is the most powerful risk factor. In case of extensive destruction, extended repair shows no benefit over replacement.

Aortic root allograft reoperations.

OBJECTIVE: To investigate outcomes after aortic root allograft reoperation, identify risk factors for morbidity and mortality, and describe practice evolution since publication of our 2006 allograft reoperation study. METHODS: From January 1987 to July 2020, 602 patients underwent 632 allograft-related reoperations at Cleveland Clinic: 144 before 2006 (early era, which suggested radical explant was superior to aortic-valve-replacement-within-allograft [AVR-only]), and 488 from 2006 to present (recent era). Indications for reoperation were structural valve deterioration in 502 (79%), infective endocarditis in 90 (14%), and nonstructural valve deterioration/noninfective endocarditis in 40 (6.3%). Reoperative techniques included radical allograft explant in 372 (59%), AVR-only in 248 (39%), and allograft preservation in 12 (1.9%). Perioperative events and survival were assessed among indications, techniques, and eras. RESULTS: Operative mortality by indication was 2.2% (n = 11) for structural valve deterioration, 7.8% (n = 7) in those with infective endocarditis, and 7.5% (n = 3) for nonstructural valve deterioration/noninfective endocarditis, and by surgical approach 2.4% (n = 9) after radical explant, 4.0% (n = 10) for AVR-only, and 17% (n = 2) for allograft preservation. Operative adverse events occurred in 4.9% (n = 18) of radical explants and 2.8% (n = 7) of AVR-only procedures (P = .2). Patients undergoing radical explants received larger valves than those undergoing AVR-only (median, 25 vs 23 mm). CONCLUSIONS: Aortic root allograft reoperations present a technical challenge but can be performed with low mortality and morbidity. Radical explant offers outcomes similar to AVR-only while allowing for implant of larger prostheses. Increasing experience with allograft reoperations has permitted excellent outcomes; thus, risk of reoperation should not dissuade surgeons from using allografts for invasive aortic valve infective endocarditis and other indications.

Aortic allograft infection risk.

OBJECTIVE: Intrinsic risk of infection of cryopreserved allograft aortic root replacements remains poorly understood despite their long history of use. The objective of this study was to determine this intrinsic risk of allograft infection and its risk factors when allografts are implanted for both nonendocarditis indications and infective endocarditis. METHODS: From January 1987 to January 2017, 2042 patients received 2110 allograft aortic valves at a quaternary medical center, 1124 (53%) for nonendocarditis indications and 986 (47%) for endocarditis indications (670 [68%] prosthetic valve endocarditis). Staphylococcus aureus caused 193 of 949 cases of endocarditis (20%), 71 (7.3%) in persons who injected drugs. Periodic surveillance and cross-sectional follow-up achieved 85% of possible follow-up time. The primary end point was allograft infection in patients with nonendocarditis and endocarditis indications. Risk factors were identified by hazard function decomposition and machine learning. RESULTS: During follow-up, 30 allografts (26 explanted) became infected in patients in the nonendocarditis group and 49 (41 explanted) in patients with endocarditis. At 20 years, the probability of allograft infection was 5.6% in patients in the nonendocarditis group and 14% in patients with endocarditis. Risk factors for allograft infection in patients in the nonendocarditis group were younger patient age and older donor age. Risk factors for allograft infection in patients with endocarditis were earlier implant year, injection drug use, and younger age. In patients with endocarditis, 18% of allograft infections were caused by the original organism. CONCLUSIONS: The low infection rates, both in patients without and with endocarditis, support continued use of allografts in the modern era, in particular for the treatment of invasive endocarditis of the aortic root.

Visualizing Staphylococcus aureus pathogenic membrane modification within the host infection environment by multimodal imaging mass spectrometry.

Bacterial pathogens have evolved virulence factors to colonize, replicate, and disseminate within the vertebrate host. Although there is an expanding body of literature describing how bacterial pathogens regulate their virulence repertoire in response to environmental signals, it is challenging to directly visualize virulence response within the host tissue microenvironment. Multimodal imaging approaches enable visualization of host-pathogen molecular interactions. Here we demonstrate multimodal integration of high spatial resolution imaging mass spectrometry and microscopy to visualize Staphylococcus aureus envelope modifications within infected murine and human tissues. Data-driven image fusion of fluorescent bacterial reporters and matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance imaging mass spectrometry uncovered S. aureus lysyl-phosphatidylglycerol lipids, localizing to select bacterial communities within infected tissue. Absence of lysyl-phosphatidylglycerols is associated with decreased pathogenicity during vertebrate colonization as these lipids provide protection against the innate immune system. The presence of distinct staphylococcal lysyl-phosphatidylglycerol distributions within murine and human infections suggests a heterogeneous, spatially oriented microbial response to host defenses.

Invasive Aortic Valve Endocarditis: Clinical and Tissue Findings From a Prospective Investigation.

BACKGROUND: Advanced aortic valve infective endocarditis (IE) with progression and destruction beyond the valve cusps-invasive IE-is incompletely characterized. This study aimed to characterize further the invasive disease extent, location, and stage and correlate macroscopic operative findings with microscopic disease patterns and progression. METHODS: A total of 43 patients with invasive aortic valve IE were prospectively enrolled from August 2017 to July 2018. Of these patients, 23 (53%) had prosthetic valve IE, 2 (5%) had allograft IE, and 18 (42%) had native aortic valve IE. Surgical findings and intraoperative photography were analyzed for invasion location, extent, and stage. Surgical samples were formalin fixed and analyzed histologically. The time course of disease and management were evaluated. RESULTS: Pathogens included Staphylococcus aureus in 17 patients (40%). Invasion predominantly affected the non-left coronary commissure (76%) and was circumferential in 15 patients (35%) (14 had prosthetic valves). Extraaortic cellulitis was present in 29 patients (67%), abscess in 13 (30%), abscess cavity in 29 (67%), and pseudoaneurysm in 8 (19%); 7 (16%) had fistulas. Histopathologic examination revealed acute inflammation, abscess formation, and lysis of connective tissue but not of myocardium or elastic tissue. Median time from onset of symptoms to antibiotics was 5 days, invasion confirmation 15 days, and surgery 37 days. Patients with S aureus had a 21-day shorter time course than patients non-S aureus. New or worsening heart block developed in 8 patients. CONCLUSIONS: Advanced invasive aortic valve IE demonstrates consistent gross patterns and stages correlating with histopathologic findings. Invasion results from a confluence of factors, including pathogen, time, and host immune response, and primarily affects the fibrous skeleton of the heart and expands to low-pressure regions.

Outcomes after resection of primary cardiac sarcoma.

Objective: To evaluate the outcomes of surgical resection of malignant primary cardiovascular tumors. Methods: From 1983 to 2018, 32 patients underwent surgical resection of malignant primary cardiovascular sarcoma at Cleveland Clinic. Mean age was 48 ± 15 years, and 19 (59%) were women. Outcomes are compared between those with complete resection and those without, and in relation to primary location. Results: The most common histologic subtypes were angiosarcoma (n = 8 [25%]) and high-grade undifferentiated sarcoma (n = 7 [22%]). Fourteen (44%) involved the left heart, 9 (28%) the right heart, 8 (25%) the pulmonary arteries, and 1 (3%) the aorta. There was clinical evidence of isolated extracardiac metastases in 8 (25%). Six (19%) patients were deemed unresectable at surgery, undergoing biopsy and palliative debulking followed by referral for definitive chemotherapy and/or radiation. The remaining 26 (81%) patients underwent 31 tumor resections with curative intent. Seven (22%) patients had previously undergone a resection or biopsy at another institution. There were 10 second-time resections, 2 third-time resections, 1 fourth-time resection, and no operative mortalities. Median survival was 3 years, with estimated survival at 6 months and 1, 5, and 10 years of 90%, 73%, 31%, and 17%, respectively. Of the 8 (25%) who were considered disease-free following surgery, 4 experienced recurrences during follow-up. Conclusions: Primary cardiac sarcoma continues to be a challenging disease with poor prognosis. Aggressive resection with curative intent, frequent surveillance for local and distant recurrence, and systemic and local multimodality treatment optimizes outcomes.

Factors associated with local invasion in infective endocarditis: a nested case-control study.

OBJECTIVE: A substantial proportion of infective endocarditis (IE) cases are complicated by local invasion. The purpose of this study was to identify patient and disease characteristics associated with local invasion in surgically treated IE patients. METHODS: This was a nested case-control study. All episodes of IE for patients admitted to Cleveland Clinic from 1 January 2013 to 30 June 2016 were identified from the Cleveland Clinic IE Registry. Patients ≥18 years of age who underwent surgery for IE were included. Among these, cases were those with local invasion, controls were those without. Local invasion, defined as periannular extension, paravalvular abscess, intracardiac fistula or pseudoaneurysm, was ascertained from the surgical operative note. Associations of selected factors with local invasion were examined in a multivariable logistic regression model. RESULTS: Among 511 patients who met inclusion criteria, 215 had local invasion. Mean age was 56 years; 369 were male. Overall 345 (68%) had aortic valve, 228 (45%) mitral valve, and 66 (13%) tricuspid or pulmonic valve involvement. Aortic valve involvement (OR 6.23, 95% CI 3.55-11.44), bioprosthetic valve (OR 3.88, 95% CI 2.36-6.44), significant paravalvular leak (OR 3.80, 95% CI 1.60-9.89), new atrioventricular nodal block (OR 3.77, 95% CI 1.87-7.90), infection with streptococci other than viridans group streptococci (OR 7.54, 95% CI 2.42-24.87) and presence of central nervous system emboli (OR 1.85, 95% CI 1.13-3.04) were associated with local invasion. DISCUSSION: Intracardiac and microorganism factors, but not comorbid conditions, are associated with local invasion in IE.

Performance and Durability of Cryopreserved Allograft Aortic Valve Replacements.

BACKGROUND: The value of allografts for aortic root replacement is controversial, with recent concern about limited durability. Currently, we prefer allografts for invasive infective endocarditis. Purposes of this study were to assess allograft performance and durability in our cumulative experience with aortic allografts. METHODS: From January 1987 to January 2017, 2042 adults received 2110 aortic allograft root replacements at our institution: 986 (47%) for infective endocarditis (669 [68%] for prosthetic valve endocarditis) and 1124 (53%) for other indications. Mean recipient age was 54 ± 15 years, and mean allograft donor age was 35 ± 13 years. Follow-up was 85% complete and comprised 17,253 patient-years of data. Longitudinal allograft performance was extracted from 6339 available echocardiographic studies. Durability was assessed by explant for allograft structural failure. RESULTS: Allograft mean gradient at hospital discharge was 6 mm Hg and 9, 13, and 15 mm Hg at 5, 10, and 15 years post-implant, respectively. Severe aortic regurgitation was 0% at hospital discharge, but 14%, 25%, and 35% at 5, 10, and 15 years, respectively. A total of 405 allografts were explanted for structural failure, actuarially 2%, 14%, 34%, and 51% at 5, 10, 15, and 20 years, respectively. Risk factors for structural failure were younger recipient age, larger body surface area, hypertension, and thoracic aorta disease; donor factors were older age and larger allograft size. Implant for infective endocarditis was not associated with accelerated structural failure. CONCLUSIONS: This study affirms allografts' long-term acceptable hemodynamic performance and durability. Concern about structural failure should not limit allograft use. Recipient hypertension, allograft size, and donor age are modifiable risk factors.

Contemporary Outcomes of Pulmonary Valve Endocarditis: A 16-Year Single Centre Experience.

BACKGROUND: Limited data exist regarding the clinical characteristics and contemporary outcomes of patients with pulmonary valve (PoV) infective endocarditis (IE). METHODS: This is a retrospective cohort study of patients with a confirmed diagnosis of IE affecting the PoV at our centre between January 2002 and October 2018. Electronic medical records were reviewed to gather the clinical and echocardiographic variables. The population was subdivided according to risk factor profiles: group 1: miscellaneous risk factors; group 2: patients with congenital heart disease (CHD); and group 3: patients who inject drugs (PWID). The primary outcome was all-cause mortality. RESULTS: Out of 2,124 cases of IE during the study period, 24 (1.1%) patients had PoV IE. The majority of cases of PoV IE occurred in patients with prosthetic valves (54.2%). Coagulase-negative Staphylococci species were the most common micro-organisms. Seventy-five per cent (75%) of the patients required surgical management. The median follow-up was 2.8 years (interquartile range: 0.2-5.3 years). Patients with miscellaneous risk factors were older (p<0.01), and had higher rates of hypertension (p=0.01) and hyperlipidaemia (p=0.04). There was a statistically significant difference in survival between the groups (p=0.03), mainly driven by better outcomes of patients with CHD, compared to those with miscellaneous risk factors. CONCLUSIONS: In a contemporary 16-year series, a high proportion of patients with PoV IE required surgical management. Patients with PoV IE and CHD had better survival, compared to patients with miscellaneous risk factors at a median follow-up of 2.8 years.

Proteomics identifies a convergent innate response to infective endocarditis and extensive proteolysis in vegetation components.

Infective endocarditis is a life-threatening infection of heart valves and adjacent structures characterized by vegetations on valves and other endocardial surfaces, with tissue destruction and risk of embolization. We used high-resolution mass spectrometry to define the proteome of staphylococcal and non-staphylococcal vegetations and Terminal Amine Isotopic Labeling of Substrates (TAILS) to define their proteolytic landscapes. These approaches identified over 2000 human proteins in staphylococcal and non-staphylococcal vegetations. Individual vegetation proteomes demonstrated comparable profiles of quantitatively major constituents that overlapped with serum, platelet, and neutrophil proteomes. Staphylococcal vegetation proteomes resembled one another more than the proteomes of non-staphylococcal vegetations. TAILS demonstrated extensive proteolysis within vegetations, with numerous previously undescribed cleavages. Several proteases and pathogen-specific proteins, including virulence factors, were identified in most vegetations. Proteolytic peptides in fibronectin and complement C3 were identified as potential infective endocarditis biomarkers. Overlap of staphylococcal and non-staphylococcal vegetation proteomes suggests a convergent thrombotic and immune response to endocardial infection by diverse pathogens. However, the differences between staphylococcal and non-staphylococcal vegetations and internal variance within the non-staphylococcal group indicate that additional pathogen- or patient-specific effects exist. Pervasive proteolysis of vegetation components may arise from vegetation-intrinsic proteases and destabilize vegetations, contributing to embolism.

Long-term Outcomes of Surgery for Invasive Valvular Endocarditis Involving the Aortomitral Fibrosa.

BACKGROUND: Reconstruction of the intervalvular fibrosa (IVF) for invasive double-valve infective endocarditis (IE) is a technically challenging operation. This study presents the long-term outcomes of two surgical techniques for IVF reconstruction. METHODS: From 1988 to 2017, 138 patients with invasive double-valve IE underwent surgical reconstruction of the IVF, along with double-valve replacement (Commando procedure, n = 86) or aortic valve replacement with mitral valve repair (hemi-Commando procedure, n = 52). Mean follow-up was 41 ± 5.9 months. RESULTS: Reoperation was required in 82% of patients, and 34% underwent emergency surgery. Pathologic features included positive blood cultures (90%), prosthetic valve IE (75%), aortic root abscess (78%), mitral annular abscess (24%), and intracardiac fistula (12%). There were 28 hospital deaths: 21 (24%) in the Commando group and 7 (14%) in the hemi-Commando group (P = .12). Overall survival at 1, 5, and 10 years was 67%, 48%, and 37%, respectively. Coronary artery disease, native valve IE, and causative organism (Staphylococcus aureus, coagulase-negative Staphylococcus, and viridans streptococci) were risk factors for late mortality. Freedom from reoperation at 1, 5, and 8 years was 87%, 74%, and 55%, respectively. Freedom from recurrent IE at 1, 5, and 8 years was 90%, 78%, and 67%, respectively. CONCLUSIONS: Although it is technically demanding, surgery for invasive IE involving IVF, which provides the only chance for cure, can be performed with reasonable clinical outcomes. In cases of IE invading the IVF and limited to the anterior mitral valve leaflet, a hemi-Commando procedure that includes mitral valve repair has improved early outcomes.

Surgical treatment of right-sided infective endocarditis.

OBJECTIVE: Right-sided infective endocarditis is increasing because of increasing prevalence of predisposing conditions, and the role and outcomes of surgery are unclear. We therefore investigated the surgical outcomes for right-sided infective endocarditis. METHODS: From January 2002 to January 2015, 134 adults underwent surgery for right-sided infective endocarditis. Patients were grouped according to predisposing condition. Hospital outcomes, time-related death, and reoperation for infective endocarditis were analyzed. RESULTS: A total of 127 patients (95%) had tricuspid valve and 7 patients (5%) pulmonary valve infective endocarditis; 66 patients (49%) had isolated right-sided infective endocarditis, and 68 patients (51%) had right- and left-sided infective endocarditis. Predisposing conditions included injection drug use (30%), cardiac implantable devices (26%), chronic vascular access (19%), and other/none (25%). One native tricuspid valve was excised, 76% were repaired or reconstructed, and 23% were replaced. Intensive care unit and postoperative hospital stays were similar among groups. Injection drug users had the best early survival (no hospital mortality), and patients with chronic vascular access had the worst late survival (18% at 5 years). Survival was worst for concomitant mitral valve versus isolated right-sided infective endocarditis or concomitant aortic valve infective endocarditis. Survival after tricuspid valve replacement was worse than after repair/reconstruction. Estimated glomerular filtration rate was the strongest risk factor for death, not predisposing condition. Eleven patients underwent 12 reoperations for infective endocarditis; more reoperations occurred in injection drug users (P = .03). CONCLUSIONS: Overall outcomes after surgery are variable and affected by patient condition, not predisposing condition. Injection drug use carries a higher risk of reoperation for infective endocarditis. Earlier surgery may permit more valve repairs and improve outcomes. Whenever possible, tricuspid valve replacement should be avoided.

Rarity of invasiveness in right-sided infective endocarditis.

OBJECTIVE: The rarity of invasiveness of right-sided infective endocarditis (IE) compared with left-sided has not been well recognized and evaluated. Thus, we compared invasiveness of right- versus left-sided IE in surgically treated patients. PATIENTS AND METHODS: From January 2002 to January 2015, 1292 patients underwent surgery for active IE, 138 right-sided and 1224 left-sided. Among patients with right-sided IE, 131 had tricuspid and 7 pulmonary valve IE; 12% had prosthetic valve endocarditis. Endocarditis-related invasiveness was based on echocardiographic and operative findings. RESULTS: Invasive disease was rare on the right side, occurring in 1 patient (0.72%; 95% confidence interval 0.02%-4.0%); rather, it was limited to valve cusps/leaflets or was superficial. In contrast, IE was invasive in 408 of 633 patients with aortic valve (AV) IE (65%), 113 of 369 with mitral valve (MV) IE (31%), and 148 of 222 with AV and MV IE (67%). Staphylococcus aureus was a more predominant organism in right-sided than left-sided IE (right 40%, AV 19%, MV 29%), yet invasion was observed almost exclusively on the left side of the heart, which was more common and more severe with AV than MV IE and more common with prosthetic valve endocarditis than native valve IE. CONCLUSIONS: Rarity of right-sided invasion even when caused by S aureus suggests that invasion and development of cavities/"abscesses" in patients with IE may be driven more by chamber pressure than organism, along with other reported host-microbial interactions. The lesser invasiveness of MV compared with AV IE suggests a similar mechanism: decompression of MV annulus invasion site(s) toward the left atrium.

Tricuspid valve endocarditis.

Right-sided infective endocarditis (RSIE) is less common than left-sided infective endocarditis (IE), encompassing only 5-10% of cases of IE. Ninety percent of RSIE involves the tricuspid valve (TV). Given the relatively small numbers of TVIE cases operated on at most institutions, the purpose of this review is to highlight and discuss the current understanding of IE involving the TV. RSIE and TVIE are strongly associated with intravenous drug use (IVDU), although pacemaker leads, defibrillator leads and vascular access for dialysis are also major risk factors. Staphylococcus aureus is the predominant causative organism in TVIE. Most patients with TVIE are successfully treated with antibiotics, however, 5-16% of RSIE cases eventually require surgical intervention. Indications and timing for surgery are less clear than for left-sided IE; surgery is primarily considered for failed medical therapy, large vegetations and septic pulmonary embolism, and less often for TV regurgitation and heart failure. Most patients with an infected prosthetic TV will require surgery. Concomitant left-sided IE has its own surgical indications. Earlier surgical intervention may potentially prevent further destruction of leaflet tissue and increase the likelihood of TV repair. Fortunately, TV debridement and repair can be accomplished in most cases, even those with extensive valve destruction, using a variety of techniques. Valve repair is advocated over replacement, particularly in IVDUs patients who are young, non-compliant and have a higher risk of recurrent infection and reoperation with valve replacement. Excising the valve without replacing, it is not advocated; it has been reported previously, but these patients are likely to be symptomatic, particularly in cases with septic pulmonary embolism and increased pulmonary vascular resistance. Patients with concomitant left-sided involvement have worse prognosis than those with RSIE alone, due predominantly to greater likelihood of invasion and abscess formation in left-sided IE. Patients with isolated TVIE have an operative mortality between 0-15% and excellent survival.

Value of surgery for infective endocarditis in dialysis patients.

OBJECTIVES: To determine the value of surgery for infective endocarditis (IE) in patients on hemodialysis by comparing the nature and invasiveness of endocarditis in hemodialysis and nonhemodialysis patients and their hospital and long-term outcomes, and identifying risk factors for time-related mortality after surgery. METHODS: From January 1997 to January 2013, 144 patients on chronic hemodialysis and 1233 nonhemodialysis patients underwent valve surgery for IE at our institution. Propensity matching identified 99 well-matched hemodialysis and nonhemodialysis patient pairs for comparison of outcomes. RESULTS: Staphylococcus aureus infection was more common in hemodialysis patients than in nonhemodialysis patients (42% vs 21%; P < .0001), but invasive disease was similar in the 2 groups (47%; P = .3). Hospital mortality was 13% and 5-year survival was 20% for hemodialysis patients, 20% below that expected in a general hemodialysis population but 15% above that of hemodialysis patients treated nonsurgically for IE. For matched patients, hospital mortality was 13% for hemodialysis patients versus 5.1% for nonhemodialysis patients (P = .05), and survival at 1 and 5 years was 56% versus 83% and 24% versus 59%, respectively (P < .004). Use of an arteriovenous graft for dialysis access (P = .01) and preoperative placement of a pacemaker (P < .0001) were risk factors for late mortality in hemodialysis patients. For matched patients, freedom from reoperation was similar in the hemodialysis and nonhemodialysis groups (P > .9). CONCLUSIONS: Intermediate-term survival after surgery for IE in hemodialysis patients is substantially worse than that in nonhemodialysis patients, but only slightly worse than that in the general hemodialysis population and substantially better than that in hemodialysis patients with IE treated nonsurgically, supporting continued surgical intervention for IE.