Surgical treatment for infective endocarditis is associated with a high mortality rate, quoted between 6–25%3,4,7−12. Risk factors associated with mortality including older age, emergent surgery, septic shock, congestive heart failure, cardiogenic shock, high risk organisms, prosthetic valve infection and stroke1, 3–12,16.
The European Society of Cardiology (ESC) provide guidelines for the management of infective endocarditis2. The guidelines advocate for early surgery in patients with heart failure, uncontrolled infection and high-risk lesions to prevent embolization2. Of all factors, congestive cardiac failure is the most consistent predictor of mortality17–18. These studies advocate for early surgery in patients presenting in heart failure17–19. Early surgery for high risk lesions is also supported by literature20–22. Of these, a randomized control trial by Kang et al demonstrated that early surgery in patients with large left sided lesions (> 10mm) significantly reduced morbidity and embolic events21. Therefore, the ESC guidelines provide a class 1 indication for early surgery in vegetations greater than 10mm with ongoing embolic phenomena. Uncontrolled infection is a further indication for early surgery. This is supported by evidence, primarily consisting of retrospective cohort studies, demonstrating that locally aggressive infection is associated with a higher mortality rate10,23. Of these, a retrospective study by Revilla et al demonstrated that persistent infection is an independent predictor of mortality, where patients who undergo urgent surgery with persistent infection are four-fold as likely to die as patients without persistent infection10. At Fiona Stanley hospital, we adopted these guidelines to help with decision making regarding operative timing.
In the current study, the in-hospital mortality rate was 5.6% or 5 out of 89 patients. This is at the lower end of the spectrum of mortality figures quoted by other studies3,4,6,9,10. A similar study conducted by Rivas de Oliveira assessed 88 surgical patients between 2005 and 2015, and reported an in-hospital mortality rate of 17%3. A study by Dunne et al in a similar Western Australian population with infective endocarditis, treated surgically, reported a mortality rate then of 13%11.
One major change reported amongst hospitals during the last decade is the establishment of a dedicated “heart team”. This team comprises of Cardiac Surgeons, Cardiologists and Infectious Diseases physicians. A dedicated “heart team” was established at Fiona Stanley Hospital since its initiation in 2015 is potentially responsible for the low mortality rate. Studies have reported a decline in mortality as a result of a multidisciplinary team (MDT) approach to endocarditis24,25. A retrospective study by Chirillo F et al demonstrated that after the implementation of an MDT, in-hospital mortality reduced from 28% to 13 %, as well as surgical mortality from 47–13%24. Similarly, a retrospective study conducted by Botelho-Nevers E. et al identified that a MDT approach to endocarditis yielded a significant decrease in one year mortality, from 18.5–8.2%25. There was also a statistically significant increase in compliance to antimicrobial therapy. The 2015 ESC guidelines (class 2 evidence) recommend the timing of surgical intervention via the consensus of an MDT team2. Our practice at Fiona Stanley Hospital is to conduct weekly MDT meetings to discuss cases of endocarditis.
Our study identified that IVDU, emergent surgery, perioperative dialysis; perioperative Inotropes, prolonged CPB time and prolonged CCT were significantly associated with in hospital mortality on univariate analysis. This finding is consistent with previous studies1,3,6,11. CPB time was the only factor to be significantly associated with death on multivariate analysis, with a mean CBP time of 250.8 vs 130.5 minutes for non-survivors and survivors respectively. Prolonged CPB time is a reflection of operative complexity, predisposes patients to end organ dysfunction, coagulation disorders and is therefore understandably associated with mortality.
In this study, factors associated with a critical perioperative state were strongly associated with post-operative mortality. Of these, perioperative dialysis was one of the major predictors of post-operative mortality, with an in-hospital mortality rate of 57% in this cohort. None of these patients required dialysis prior to their presentation with endocarditis. Studies of patients requiring perioperative dialysis, although chronic, reported a mortality rate of 40%26. Elevated peri-operative creatinine clearance is also associated with increased post-operative mortality however did not reach significance in this study 3. Likewise, perioperative inotrope requirement was also associated with mortality post operatively, and reflects the challenges associated with operating on patients in shock.
Embolic phenomena occurred 39 patients (43.8%). The most common site of emboli was the brain (22 patients) followed by skin and lungs. Other studies have also quoted equally high rates of embolic events10,27. Likewise, in these studies, the brain was the most common site of embolism10,27. Pre-operative stroke is a highly relevant complication of infective endocarditis due to the risk of hemorrhagic transformation and postoperative neurological deterioration. Guidelines provide class 2A evidence to delay surgery by a month in the presence of intracranial haemorrhage2. As a result, we adopted a low threshold to conduct a CT brain, explaining the higher rate of cerebral emboli compared to other sites in this study. Embolic phenomena and cerebral emboli were linked to the incidence of preoperative stroke on univariate analysis, however was not associated with in-hospital mortality.
In terms of organism, Staphylococcus Aureus was most commonly cultured and present in 39% of patients. This was followed by Enterococcus Faecalis and Streptococcus Mitis in 20% and 9% of patients respectively. Eleven percent of patients had culture negative infective endocarditis. The prevalence of Staphylococcus Aureus is a feature in other studies also6,10,. There has been a reported shift in the epidemiology of infective endocarditis, away from Streptococcus species and HACEK (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens and Kingella) organisms towards Staphylococcus Aureus28,29. This was also evident in our study, with only 15 patients culturing Viridians Streptococci. There was one case of HACEK endocarditis. Staphylococcus Aureus has been linked to a higher mortality rate in surgically treated endocarditis30,31. It is also linked to locally aggressive infection, higher rates of embolization and septic shock30,31.Other studies do not demonstrate a relationship between Staphylococcus Aureus and mortality or morbidity1,3,6,10,. Our study also did not demonstrate a relationship between Staphylococcus Aureus and in-hospital mortality as well as post-operative complications. Our institution favors early surgery for patients with Staphylococcus Aureus endocarditis.
Complications after surgery for infective endocarditis were not uncommon. Ten patients (11%) had a postoperative stroke. Identifiable risk factors were cerebral emboli, pre-operative creatinine, perioperative cardiogenic shock, perioperative respiratory failure, perioperative ionotropic requirement and emergent procedure. Other studies have demonstrated a similar incidence of post-operative stroke10,11,27. Only one other study investigated risk factors associated with post-operative stroke11. Post-operative stroke is a debilitating issue, and some centers advocate for delaying surgery to minimize the risk of hemorrhagic transformation22,31. Others demonstrate that the overall mortality benefit from early surgery outweighs this risk33. The practice at Fiona Stanley Hospital was to delay surgery by a month if feasible if there is a significant risk of hemorrhagic transformation. A total of 19 patients (21%) required dialysis postoperatively. On multivariate analysis, cardiogenic shock and pre-operative dialysis were independently associated with the incidence of post-operative dialysis. Post-operative renal failure is linked to a critical perioperative state and is associated with an increased risk of mortality6,10,34,35. Conduction abnormalities are an early indication of an infectious process expanding to involve the membranous interventricular septum, often in cases with aortic valve endocarditis. A total of 11 patients (12%) had complete heart block, all of whom received a pacemaker. The incidence of which is comparable to that published in other studies6,36.
This is a retrospective observational study with inherent biases in data collection. A larger prospective study may enable us to explore more factors associated with mortality and morbidity. Our small patient numbers and the small number of in-hospital deaths have limited the use of multivariate analysis to evaluate risk factors for in-hospital mortality. Fiona Stanley Hospital is a new institution, and data is available over a period of 4 years. As a result, long term morbidity and survival data was not explored by this study and therefore Kaplan-Meier survival data was not conducted. A long term follow up of our patients would be beneficial to assess whether the low in-hospital mortality rate is also translated into long term survival.