Endocarditis: the Cinderella of Cardiology is back!

For the podcast associated with this article, please visit https://academic. oup.com/eurheartj/pages/Podcasts. When in 1911 the famous composer Gustav Mahler acquired endocarditis on his mitral valve damaged by rheumatic fever in his youth, there was no treatment available.1 Mahler died a few weeks after his first fever spells in New York upon arrival in Vienna. In spite of a marked reduction in rheumatic fever, endocarditis remains an important underinvestigated cardiac condition with distinct risk factors for its occurrence such as congenital heart disease,2 valve prosthesis,3 and previous endocarditis, among others.4,5 Its morbidity and mortality remain high due to septic embolization,6,7 paravalvular leaks,8 and valve incompetence or destruction. The EURO-ENDO registry aimed to study its current management and outcomes, as reported in their FAST TRACK ‘Clinical presentation, aetiology, and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study’ by Gilbert Habib and colleagues from the Hopital Timone in Marseille, France.9 This prospective cohort enrolled 3116 adult patients admitted with a diagnosis of infective endocarditis based on ESC 2015 diagnostic criteria. Endocarditis involved native valves in 56.6% and prosthetic valves in 30.1%, and 9.9% were device related; it was community acquired in 65.66%. Microorganisms were staphylococci in 44.1%, oral streptococci in 12.3%, enterococci in 15.8%, and Streptococcus gallolyticus in 6.6%. [18F]Fluorodeoxyglucose positron emission tomography with computed tomography10,11 was performed in 16.6% and extra-cardiac uptake was observed in 43%, with a better sensitivity in prosthetic valves (67%) than in native valves (28%) and in device-related endocarditis (16%). Embolic events occurred in 21%, and were significantly associated with tricuspid or pulmonary endocarditis, presence of a vegetation, and Staphylococcus aureus. According to ESC guidelines, cardiac surgery was indicated in 69.3%, but was finally performed in only three-quarters of them (Figure 1). In-hospital death occurred in 17.1% and was more frequent in prosthetic valve endocarditis. Independent predictors of mortality were Charlson index, creatinine >2 mg/dL, congestive heart failure, vegetation length >10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Thus, infective endocarditis is still a life-threatening disease with frequently lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles, a conclusion that is further discussed in an Editorial by Jose M. Miro from the Hospital Clinic – IDIBAPS in Barcelona, Spain.12 Prognosis of infective endocarditis is dismal when cardiac surgery is indicated but not performed (adjusted Kaplan–Meier curve) (from Habib G, Erba PA, Iung B, Donal E, Cosyns B, Laroche C, Popescu BA, Prendergast B, Tornos P, Sadeghpour A, Oliver L, Vaskelyte J-J, Sow R, Axler O, Maggioni AP, Lancellotti P, on behalf of the EURO-ENDO Investigators. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO(European infective endocarditis) registry: a prospective cohort study. See pages 3222–3232). Prognosis of infective endocarditis is dismal when cardiac surgery is indicated but not performed (adjusted Kaplan–Meier curve) (from Habib G, Erba PA, Iung B, Donal E, Cosyns B, Laroche C, Popescu BA, Prendergast B, Tornos P, Sadeghpour A, Oliver L, Vaskelyte J-J, Sow R, Axler O, Maggioni AP, Lancellotti P, on behalf of the EURO-ENDO Investigators. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO(European infective endocarditis) registry: a prospective cohort study. See pages 3222–3232). Increasing attention has been given to the risk of infective endocarditis in patients with certain blood stream infections. In their article entitled ‘Prevalence of infective endocarditis in patients with positive blood cultures: a Danish nationwide study’, Lauge Klement Moltke Østergaard and colleagues from the Rigshospitalet in Copenhagen, Denmark aimed to investigate the prevalence of infective endocarditis in blood stream infections with bacteria typically associated with infective endocarditis.13 Out of 69 021 patients, those with Enterococcus faecalis had the highest prevalence of infective endocarditis (16.7%) followed by S. aureus (10.1%), Streptococcus spp. (7.3%), and coagulase-negative staphylococci (1.6%) (Figure 2). Throughout the study period, the prevalence of infective endocarditis among patients with E. faecalis and Streptococcus spp. increased significantly. Male patients had a higher prevalence of infective endocarditis with E. faecalis, Streptococcus spp., and coagulase-negative staphylococci compared with females. An increase in the prevalence of endocarditis was seen for E. faecalis, Streptococcus spp., and coagulase-negative staphylococci with increasing age. Thus, with E. faecalis blood stream infection, 1 in 6 had infective endocarditis, this was 1 in 10 for S. aureus, and 1 in 14 for Streptococcus spp., suggesting that screening for infective endocarditis seems reasonable in patients with such bacteria in the blood stream. These results are put into context in an Editorial by Bernard Iung from the Bichat Hospital in Paris, France.14 Percentage of total blood stream infections with infective endocarditis is shown. CoNS, coagulase negative staphylococci; IE, infective endocarditis (from Østergaard L, Bruun NE, Voldstedlund M, Arpi M, Andersen CØ, Schønheyder HC, Lemming L, Rosenvinge F, Valeur N, Søgaard P, Andersen PS, Skov R, Chen M, Iversen K, Gill S, Lauridsen TK, Dahl A, Oestergaard LB, Povlsen JA, Moser C, Bundgaard H, Køber L, Fosbøl EL. Prevalence of infective endocarditis in patients with positive blood cultures: a Danish nationwide study. See pages 3237–3244). Percentage of total blood stream infections with infective endocarditis is shown. CoNS, coagulase negative staphylococci; IE, infective endocarditis (from Østergaard L, Bruun NE, Voldstedlund M, Arpi M, Andersen CØ, Schønheyder HC, Lemming L, Rosenvinge F, Valeur N, Søgaard P, Andersen PS, Skov R, Chen M, Iversen K, Gill S, Lauridsen TK, Dahl A, Oestergaard LB, Povlsen JA, Moser C, Bundgaard H, Køber L, Fosbøl EL. Prevalence of infective endocarditis in patients with positive blood cultures: a Danish nationwide study. See pages 3237–3244). The pathogenesis of endocarditis is not well understood, resulting in unsuccessful attempts at prevention. Clinical observations suggest that S. aureus infects either damaged or inflamed heart valves. In their Basic Science article ‘Staphylococcus aureus endocarditis: distinct mechanisms of bacterial adhesion to damaged and inflamed heart valves’, Peter Verhamme and colleagues from the University Hospitals Leuven in Belgium studied the initial adhesion of S. aureus in both risk states using a newly developed endocarditis mouse model.15 Both cardiac valve damage and inflammation predisposed to endocarditis, but by distinct mechanisms. Following valve damage, S. aureus adhered directly to von Willebrand factor and fibrin, deposited on the damaged valve. This was mediated by Sortase A-dependent adhesins such as von Willebrand factor-binding protein and Clumping factor A, while platelets did not contribute. In contrast, upon cardiac valve inflammation, widespread endothelial activation led to release of endothelial cell-bound von Willebrand factor. This recruited large amounts of platelets, capturing S. aureus on the valve surface. Here, neither fibrinogen nor Sortase A was essential. Thus, cardiac valve damage and inflammation predispose to S. aureus endocarditis via distinct mechanisms. These findings may have important implications for the development of new preventive strategies, as some interventions might be effective in one risk state, but not in the other, a conclusion that is further discussed in an Editorial by Zerelda Esquer Garrigos from the Mayo Clinic in Rochester, Minnesota (USA).16 Transcatheter aortic valve implantation (TAVI), now a common procedure to treat high-risk patients with severe aortic stenosis,17,–19 has been rapidly expanding into younger and lower risk populations,20 creating a need to better understand long-term outcome after TAVI. Endocarditis has also been described in this patient group,21 but its true incidence is unknown. In their FAST TRACK entitled ‘Infective endocarditis after transcatheter aortic valve implantation: a nationwide study’, Henrik Bjursten and colleagues from the Lunds Universitet in Sweden sought to determine the incidence, risk factors for, presentation of, and outcome after prosthetic valve endocarditis in 4340 patients treated with TAVI.22 The risk for prosthetic valve endocarditis after TAVI was 1.4% in the first year and 0.8% per year thereafter. One-year survival after prosthetic valve endocarditis diagnosis was 58%, and 5-year survival was 29%. Body surface area, estimated glomerular filtration rate <30 mL/min/1.73 m2, critical pre-operative state, mean pre-procedural valve gradient, amount of contrast dye used, transapical access, and atrial fibrillation were identified as independent risk factors for prosthetic valve endocarditis. Staphylococcus aureus was more common in early (<1 year) prosthetic valve endocarditis, which was associated with root abscess and late prosthetic valve endocarditis. Furthermore, community acquisition was associated with higher 6-month mortality. Thus, the incidence of prosthetic valve endocarditis is similar to that of surgical bioprostheses. Compromised renal function was a strong risk factor for developing prosthetic valve endocarditis. In the context of prosthetic valve endocarditis, TAVI seems to be a safe option for patients. These results are further discussed in a interesting Editorial by Jose Zamorano from Madrid, Spain.23 This issue is complemented by two Discussion Forum contributions. In a contribution entitled ‘Childhood infection may mediate the relationship between suboptimal intrauterine growth, preterm birth, and adult cardiovascular disease’, Siroon Bekkering and colleagues from the Radboud University Medical Center in Nijmegen, The Netherlands comment on the recently published clinical review article entitled ‘Mechanisms linking preterm birth to onset of cardiovascular disease later in adulthood’ by Jawahar L. Mehta from the University of Arkansas in Little Rock, Arizona (USA) and colleagues.24,25 Mehta et al. respond to Bekkering and colleagues in a separate response.26 The editors hope that this issue of the European Heart Journal will be interest to its readers. With thanks to Amelia Meier-Batschelet for help with compilation of this article.