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Infective endocarditis: we could (and should) do better
  1. Paul Richard Scully1,2,
  2. Simon Woldman3,
  3. Bernard D Prendergast1
  1. 1 Cardiology Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  2. 2 Institute of Cardiovascular Sciences, University College London, London, UK
  3. 3 Barts Heart Centre, St Bartholomew’s Hospital, London, UK
  1. Correspondence to Dr Bernard D Prendergast, Cardiology Department, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; bernard.prendergast{at}gstt.nhs.uk

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Infective endocarditis (ie, the infection of a native or prosthetic heart valve, the endocardium or implanted cardiac device1) is a clinical chameleon whose epidemiology and natural history are in constant evolution, reflecting the complex interaction between an ageing population, elusive microorganisms, evolving patterns of healthcare, available therapies and the application of aggressive surgery. Despite overall advances in treatment, there is no consistent signal of falling incidence and clinical outcomes remain poor.

IE is uncommon with a generally accepted overall annual incidence of 3–10 cases per 100 000 people.1 However, recent data indicate that this incidence has increased significantly in England where IE admissions (primary ICD-10 diagnostic code I33) remained stable between 1998–1999 (26.6 cases/million) and 2009–2010 (26.9 cases/million) but rose dramatically (by 86%) to 50.0 cases/million in 2018–2019 (figure 1).2 While some of this increase may partly relate to recommendations by the National Institute for Health and Care Excellence in 2008 regarding the cessation of antibiotic prophylaxis in at-risk individuals undergoing selected dental and other invasive medical procedures,3 this association cannot be confirmed in the absence of microbiological data. Indeed, multiple contributory factors are likely, including (A) an ageing population, (B) increased use of both intra-cardiac (including permanent pacemakers, implantable cardioverter-defibrillators, surgical and transcatheter heart valves) and vascular devices (including those used for chronic haemodialysis), (C) epidemic levels of opioid addiction and associated injection drug use, (D) emergence of staphylococci and enterococci (neither of which are targeted by current antibiotic prophylaxis strategies) as more common causative organisms, and (E) greater clinical awareness of IE. Nevertheless, these findings are disturbing and contrast with reports of falling incidence in the USA4 and falling or more modest increases in Europe.5 European guidelines still provide a Class IIA recommendation for the use of antibiotic prophylaxis in patients at highest risk of IE undergoing specific dental procedures,6 which is similar to the American Heart Association guidelines from 2007 (although there is little reference to this controversial topic in their most recent scientific statement).7

Figure 1

English hospital admissions with a primary diagnosis of infective endocarditis (ICD-10, I33.0) from 2008 to 2019 (corrected for population growth).2 Reprinted from The Lancet, 395, Thornhill MH, Dayer MJ, Nicholl J, et al, An alarming rise in incidence of infective endocarditis in England since 2009: why?, 1325–7, 2020, with permission from Elsevier.

In this edition of Heart, Kim et al 8 report the findings of a retrospective cohort study from a single specialist referral centre in South Korea (a nation where antibiotic prophylaxis policies reflect those of the USA), and demonstrate a steady increase in the incidence of IE over a 12-year period, accompanied by a progressive fall in mortality. The overall in-hospital mortality rate was 14.6%. Aortic valve IE, Staphylococcus aureus infection, neurological complications, multi-organ involvement or high comorbidity index were predictive of adverse outcome. Conversely, surgical intervention was predictive of reduced mortality and improved long-term prognosis (figure 2).8

Figure 2

Clinical and microbiological trends contributing to increasing incidence and falling mortality of infective endocarditis in South Korea.8 AUC, area under the curve; SOFA, sequential organ failure assessment.

These observations are consistent with other recently reported series. While staphylococcal, streptococcal and enterococcal species are responsible for 80%–90% of cases,1 9 Staphylococcus aureus is the most common causative organism in developed countries (accounting for 30%–35% of caseload).9 Indeed, healthcare-acquired IE now accounts for around 25% of cases as a consequence of increased use of indwelling lines and invasive procedures.9 Despite improvements in diagnosis and management, outcomes remain poor with in-hospital and 6-month mortality of 18% and 30%, respectively,1 9 S. aureus infection is one of the principal determinants of outcome, alongside advancing age, persistently positive blood cultures (despite appropriate antibiotic therapy) and the presence of significant comorbidities.1 6 9

Preventative measures beyond antibiotic prophylaxis remain essential, including meticulous attention to dental and cutaneous hygiene, maintained focus on the reduction of hospital acquired IE (particularly staphylococcal and enterococcal infection) and innovative measures to reduce biofilm formation. Initial treatment focuses on early instigation of appropriate antibiotic therapy guided by microbiological findings and careful consideration of the need for surgery (and its timing). The choice of regime and its duration depend on the clinical scenario and bacterial sensitivities, and should be made in conjunction with the microbiology team. In general terms, treatment is longer for patients with prosthetic valve IE (at least 6 weeks) than those with native valve IE (typically 2–6 weeks) and simplified oral regimes may be appropriate in an increasing proportion of patients.10 Surgery is required in up to 50% of patients for heart failure, uncontrolled infection or prevention of systemic embolism (box 1).6 Accumulating evidence demonstrates the benefits of early intervention11 and surgery involving aggressive resection of infected tissue (and valve repair when feasible) should be undertaken by experienced surgical teams working in specialist centres.

Box 1

Indications for surgery in infective endocarditis.6

Surgery for left-sided endocarditis can be considered for:

Heart failure

  1. Cardiogenic shock or refractory pulmonary oedema in patients with aortic or mitral (native or prosthetic) infective endocarditis and severe regurgitation, obstruction or fistula (Emergency).

  2. Symptoms of heart failure or echocardiographic signs of poor tolerance in patients with aortic or mitral (native or prosthetic) infective endocarditis and severe regurgitation or obstruction (Urgent).

Uncontrolled infection

  1. Local (abscess, false aneurysm, fistula, enlarging vegetation) (Urgent).

  2. Infection due to a multi-resistant organism or fungi (Urgent/Elective).

  3. Persistently positive blood cultures despite appropriate antibiotics and adequate control of septic metastatic spread (Urgent).

  4. Prosthetic valve endocarditis caused by staphylococci or non-HACEK gram-negative bacteria (Urgent/Elective).

Prevention of systemic embolism

  1. Aortic or mitral (native or prosthetic) valve endocarditis and persistent vegetations >10 mm after ≥1 embolic episode despite appropriate antibiotics (Urgent).

  2. Aortic or mitral (native or prosthetic) valve endocarditis with vegetations >10 mm and severe valve stenosis or regurgitation and low operative risk (Urgent).

  3. Aortic or mitral (native or prosthetic) valve endocarditis with isolated very large (>30 mm) vegetations (Urgent).

  4. Aortic or mitral (native or prosthetic) valve endocarditis with isolated large vegetations (>15 mm) and no other indication for surgery (Urgent).

Surgery for right-sided endocarditis is much less commonly performed, but can be considered in cases where:

  1. Microorganism is particularly difficult to eradicate (eg, fungi) or persistent bacteraemia (>7 days) despite appropriate antibiotics, or

  2. Persistent tricuspid valve vegetations (>20 mm) after recurrent pulmonary emboli, or

  3. Right heart failure secondary to severe tricuspid regurgitation with poor response to diuretics.

Given that IE is frequently a multisystem disease requiring the input of a number of specialists, the involvement of a dedicated Endocarditis Team is a key element in modern management. This team, comprising cardiologists with a specialist interest in valvular heart disease and cardiac imaging, cardiothoracic surgeons and microbiologists (supported by the availability of electrophysiologists, specialists in adult congenital heart disease, neurologists and spinal surgeons when required for individual patients), should meet regularly (at least weekly, with opportunity for additional ad hoc discussions when required) and work to agreed protocols for medical and surgical management. Relapse and recurrence are not infrequent and deferred surgery is often required for residual valve lesions—the Endocarditis Team should therefore also oversee follow-up at 1, 3, 6 and 12 months after admission in a specialised Endocarditis or Heart Valve clinic with ready access to imaging, microbiological and surgical expertise.6 This approach, which is strongly supported by international guidelines,6 7 has been shown to reduce 1-year mortality by more than 50% in one study (18.5% to 8.2%)12 and is arguably the single most important step forward in the management of IE in the past 20 years.

As the present data from South Korea demonstrate, IE remains associated with poor outcomes and its incidence is increasing in many countries around the world. Greater public health awareness is warranted alongside renewed emphasis on education of patients at risk (with particular regard to prompt symptom reporting and maintenance of good oral and cutaneous hygiene), early diagnosis, timely referral and specialist care. Once suspected or diagnosed, early involvement of a dedicated Endocarditis Team is essential in managing these patients combined with early, appropriate antibiotic therapy and decisions regarding the need for surgery and its timing.

References

Footnotes

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  • Contributors All authors have contributed significantly to the writing of this Editorial.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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