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Article

The Impact of Critical Illness on the Outcomes of Cardiac Surgery in Patients with Acute Infective Endocarditis

by
Mbakise P. Matebele
1,2,3,4,
Kanthi R. Vemuri
1,2,
John F. Sedgwick
1,2,
Lachlan Marshall
1,2,
Robert Horvath
1,2,
Nchafatso G. Obonyo
1,2,4 and
Mahesh Ramanan
1,5,6,*
1
Metro North Hospital and Health Services, Queensland Health, Brisbane, QLD 4032, Australia
2
Mayne Medical School, The University of Queensland, Brisbane, QLD 4006, Australia
3
School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215, Australia
4
Critical Care Research Group, Brisbane, QLD 4032, Australia
5
Queensland University of Technology, Brisbane, QLD 4059, Australia
6
The George Institute for Global Health, University of New South Wales, Sydney, NSW 2000, Australia
*
Author to whom correspondence should be addressed.
Hearts 2025, 6(2), 15; https://doi.org/10.3390/hearts6020015
Submission received: 30 March 2025 / Revised: 2 June 2025 / Accepted: 3 June 2025 / Published: 6 June 2025
Review Reports Versions Notes

Abstract

:
Background: This study aims to evaluate the impact of critical illness, defined as the need for preoperative intensive care unit (ICU) admission for invasive monitoring or organ support, on cardiac surgery outcomes for patients with acute infective endocarditis (IE). Methods: A retrospective analysis of prospectively collected data from patients treated between 1 January 2017 and 30 May 2024 at a single Australian tertiary cardiothoracic centre was performed. Data were collected from the Australian and New Zealand Cardiothoracic Society (ANZCTS) database and the Australian and New Zealand Intensive Care Adult Patients Database (ANZICS-APD). Results: Among 342 patients who underwent cardiac surgery for IE, 32 (9.4%) were critically ill. The critically ill patients were admitted to the ICU before surgery with a diagnosis of septic or cardiogenic shock, with 86% (n = 30) requiring mechanical ventilation. Compared to the non-critically ill cohort, critically ill patients were more likely to have a history of intravenous drug use (IVDU) (41% vs. 14%, p = 0.03) and a younger age (median age 49 years [42–56] vs. 61 years [44–70], p = 0.03), and although methicillin-sensitive Staphylococcus aureus (MSSA) was the most common causative organism in both groups, it was found significantly more often in the critically ill cohort (66% and 27%, p = 0.001). The median EuroSCORE II was comparable between the groups (2.1 [1.3–10] vs. 2.8 [1.3–5.7], p = 0.69); however, the APACHE III (57 [49–78] vs. 52 [39–67], p = 0.03) and ANZROD scores (0.04 [0.02–0.09] vs. 0.013 [0.004–0.038], p = 0.00002) were significantly higher in the critically ill patients. The overall 30-day mortality rates were similar between the groups (13% vs. 5%, p = 0.60). The median ICU length of stay (LOS) was significantly longer for the critically ill patients (5 days [IQR 2–10 days] vs. 2 days [1–4 days], p = 0.0004), with a similar hospital LOS (23 days [IQR 14–36] vs. 21 days [12–34], p = 0.46). Renal replacement therapy was three times higher in the critically ill (34% vs. 11%, p = 0.0001). Reoperations for bleeding were similar between the groups (16% vs. 11%, p = 0.74). Conclusions: Despite being associated with higher ANZROD and APACHE III scores, a longer ICU length of stay, and higher use of renal replacement therapy, critical illness did not have an impact on the EuroSCORE II, hospital length of stay, or reoperation rates for bleeding or 30-day mortality among patients with IE undergoing cardiac surgery. The lessons from this study will guide and inform the development of better infective endocarditis databases and registries.

1. Introduction

Infective endocarditis (IE) is a rare, and often fatal, infection that involves the endocardium, heart valves, or intracardiac devices. The Australian incidence is highest amongst octogenarians (4.7 per 100,000) [1]. The overall in-hospital mortality rate is reported at between 10 and 30% [2,3].
Data from the Global Burden of Disease study (GBD) 2019 showed that the age-standardised incidence rate (ASIR) of IE diagnosed in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019, and this was comparable with the global trend (from 9.91/100,000 population in 1990 to 13.8 in 2019) [4]. The most severe form of the disease requires admission of patients to the intensive care unit (ICU). Although there is no universal definition of critical illness, patients admitted to the ICU with IE prior to cardiac surgery are considered critically ill because they are at risk of death without organ support. Few studies describe the impact of critical illness on the outcomes of these patients [5,6,7,8]. Some studies on patients admitted to the ICU have reported an in-hospital mortality that ranges from 35% in surgically treated patients to 84% in medically treated patients [9,10].
The objective of this study was to describe the impact of critical illness on the outcomes of patients undergoing surgery for acute infective endocarditis at a tertiary cardiothoracic referral hospital in Queensland, Australia.

2. Materials and Methods

This retrospective observational study was conducted and reported according to the “The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies” [11].
Data were collected from the Australian and New Zealand Cardiothoracic Society (ANZCTS) database and Australian and New Zealand Intensive Care Society Adult Patients Database (ANZICS-APD). This was a retrospective analysis of prospectively collected data from patients who underwent cardiothoracic surgery at a single tertiary cardiothoracic centre in Australia between 1 January 2017 and 30 May 2024, with a diagnosis of definite IE or possible IE (according to the modified Dukes diagnostic criteria) [12].
Patients were divided into two cohorts based on the timing of their ICU admission relative to cardiac surgery:
In the critically ill cohort were patients admitted to the ICU prior to cardiac surgery. These patients were admitted for organ support and/or close monitoring due to clinical deterioration or a high perioperative risk. In the non-critically ill cohort were patients admitted to the ICU after cardiac surgery as part of routine postoperative care.
For the purposes of this study, critical illness was operationally defined as ICU admission prior to cardiac surgery. This definition aligns with the conceptual framework proposed by Kayambankadzanja et al., who described critical illness as “a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided, and the potential for reversibility” [13]. Although no universally accepted criteria exist, this pragmatic definition was used to distinguish patients requiring preoperative intensive care.
There are currently no objective criteria to define critical illness; however, the APACHE III-J score was used to calculate the baseline severity of illness prior to surgery. The specific reasons for ICU admission were also extracted, where available, and are presented in the results section.
Inclusion criteria:
Adult patients older than eighteen years with a diagnosis of infective endocarditis and who had undergone cardiac surgery for infective endocarditis.
Exclusion criteria:
Patients with infective endocarditis who did not undergo cardiac surgery, as this study focused on surgical outcomes. Patients with contraindications to surgery (e.g., advanced age, significant comorbidities) or those managed medically due to mild disease. Patients with a history of endocarditis unrelated to the current cardiothoracic surgery.
Definitions:
The definitions for the urgency of surgery were classified according to the Australian and New Zealand Society of Cardiac & Thoracic Surgeons (ANZCTS) database. The database is funded by the Victorian Department of Health, NSW Clinical Excellence Commission (CEC), Queensland Health, and participating units and its aim is to collect information on all adults having heart surgery in Australia and New Zealand in an effort to monitor and improve the results of cardiac surgery. The definitions for acute renal failure were as per the ANZICS-APD dictionary.
ANZCTS definitions:
Elective: The procedure could be deferred without risk of a compromised cardiac outcome.
Urgent: The procedure was performed as follows:
(a) Within 72 h of an unplanned admission (patient who had a previous angiogram and was scheduled for surgery but was admitted acutely);
(b) During the same hospitalisation in a clinically compromised patient in order to minimise the chance of further clinical deterioration.
Emergency: Unscheduled surgery required in the next available theatre on the same day (as admission) due to refractory angina or haemodynamic compromise.
Salvage: The patient underwent cardiopulmonary resuscitation en route to or in the operating room, prior to surgical incision.
The European System for Cardiac Operative Risk Evaluation (EuroSCORE-II) score was used for quantification of the cardiac surgical risk of death [14].
ANZROD: Australian and New Zealand Risk of Death (ANZROD) score. A risk-adjustment tool for benchmarking performance and detecting outliers in Australian and New Zealand intensive care units [15]. This score was calculated based on first 24 h from the time of admission to the ICU. The score is calculated as a percentage risk of death. It was used as a tool to predict the risk of death for critically ill patients.
APACHE III-J: The Acute Physiology and Chronic Health Evaluation (APACHE) III-J model. This is a prognostic tool used in intensive care units (ICUs) to predict the risk of hospital death for severely ill patients. The score is calculated based on the first 24 h from the time of admission to the ICU. It assigns a score between 0 and 299, with higher scores indicating a greater risk of mortality. A five-point increase in the score is associated with a statistically significant increase in the relative risk of death [16].
Acute Renal Failure: This was defined by ANZICS APD dictionary criteria—In the first 24 h in the ICU, a urine output < 410 mls AND creatinine >133 micromoles/L AND patient is not receiving chronic dialysis prior to their admission to hospital.
Outcomes
The primary exposure variable was the timing of ICU admission relative to cardiac surgery, used to define critical illness as described above. The primary endpoint was 30-day mortality. The secondary endpoints were reoperation rate, ICU length of stay, hospital length of stay, and renal replacement therapy. The EuroSCORE II was used to quantify the operative risk.
Statistical Analysis
The patients’ records were accessed and evaluated for clinical outcomes, illness severity scores, and surgical intervention. Analyses were conducted using STATA™ (V.18). Data are presented as medians (IQRs), and an alpha value of p < 0.05 was considered statistically significant. Descriptive summaries of the data are presented. Depending on the normality or skewness of the data distribution, continuous variables are expressed as a mean and standard deviation or median and interquartile range, respectively. Categorical variables are expressed in percentages. Student’s t-test or the Mann–Whitney U-test was used to compare continuous data between groups, and Fisher’s exact test to compare categorical data. A multivariate analysis model of continuous variables that demonstrated significance in the univariate analysis was generated to correctly assess the association between the variables and the endpoints. The following fixed effects were adjusted for during the multivariable analysis: age at surgery, EuroSCORE II risk, time before surgery, ICU length of stay, and hospital length of stay.
Any missing data were handled using multivariate imputation by chained equations (MICE).

3. Results

Table 1 displays the characteristics of patients who underwent cardiac surgery for infective endocarditis (IE). Out of 342 patients who underwent surgery for IE, 32 (9%) were classified as critically ill. The proportion of females was similar between the critically ill and non-critically ill groups, at 25% and 22%, respectively. Although the median EuroSCORE II was similar between the two cohorts (2.1 [1.3–10] vs. 2.8 [1.3–5.7], p = 0.69), critically ill patients had a higher percentage in the high-risk category (>8) compared to non-critically ill patients (31% vs. 18%), though not statistically significant. The critically ill patients had a higher median ANZROD score (0.04, [0.024–0.090], p = 0.00002) compared to non-critically ill patients (0.013, [0.004–0.038]), with a wider interquartile range suggesting greater variability in risk among the critically ill. The median APACHE III-J score was also higher in critically ill compared to the non-critically ill patients (57 [49–78] vs. 52 [39–67], p = 0.03), again suggesting high illness acuity.
A larger proportion of critically ill patients had moderate or severe (13% and 6%) LV dysfunction compared to non-critically ill patients (4% and 1%, respectively), suggesting preoperative cardiac failure. However, the preoperative left ventricular (LV) function was similar between the groups, with the majority of patients having an LV ejection fraction greater than 50% (72% vs. 84%, p = 0.14). There was also a trend towards higher NYHA III/IV classification in the critically ill patients compared to the non-critically ill patients (39% vs. 24%), indicating a greater severe functional limitation preoperatively. The incidence of acute renal failure on admission to the ICU was similar between the two cohorts (9% vs. 5%, p = 0.28). Critically ill patients were younger (median age of 49 years [IQR 42–56 years] vs. 61 years [42–56 years], p = 0.06) and were more likely to have a history of intravenous drug use (IVDU) (41% vs. 14%, p = 0.03). Native valves were the most common type of valve infected in both groups. The isolated aortic valve was the most commonly affected, with similar involvement in both cohorts (32% vs. 35%, p = 0.85). Aortic and mitral valves were the most affected valves in both cohorts, but isolated mitral valve infections were higher in non-critically ill patients. Tricuspid valve and other valve infection combinations (10% and 22%, respectively) appeared disproportionately higher in critically ill patients. Pulmonic valve infections remained rare across both groups. Overall, left-sided native valve IE accounted for the majority of cases in both cohorts.
The median time to surgery was similar in both cohorts (3.5 days [1.5–8 days] vs. 3 days [1–9 days], p = 0.98). Most critically ill patients underwent urgent surgery (72% vs. 64%, p = 0.45). It was observed that 22% of critically ill patients underwent elective surgery, suggesting that these patients likely experienced a delay in surgery to optimise their condition, or they may have required additional interventions for complications associated with infective endocarditis, such as neurosurgical procedures.
Regarding primary and secondary outcomes of patients with infective endocarditis, as shown in Table 2, the 30-day mortality rates were similar between the critically ill and non-critically ill patients (13% vs. 5%, p = 0.60). Critically ill patients had a longer median ICU (LOS) (5 days [IQR 2–10 days] vs. 2 days [IQR 1–4 days], p = 0.0004). To eliminate preoperative bias, when the ICU LOS was measured from the surgery date until discharge from the ICU, critically ill patients had a longer ICU LOS (6 days [IQR 3–11 days] vs. 3 days [IQR 2–5 days], p = 0.001). However, the median hospital length of stay (LOS) was similar between the two groups (23 days [IQR 14–36] vs. 21 days [IQR 12–34], p = 0.46). Critically ill patients had a higher frequency of renal replacement therapy than the non-critically ill patients (34% vs. 11%, p = 0.0001). The rate of reoperation was also similar between the groups (25%vs. 29%, p = 0.81) as well as reoperations for bleeding (16% vs. 11, p = 0.74) respectively.
Methicillin-sensitive Staphylococcus aureus (MSSA) was the most common causative organism in both groups, but it was more prevalent in critically ill patients (66% vs. 27%, p = 0.001), as shown in Table 3. Supplementary Table S1 shows an extended list of organisms that were isolated.
Culture-negative endocarditis was more common in non-critically ill patients (12.9% vs. 3.1%). Enterococcus faecalis and Streptococcus mitis were more frequent in the non-critically ill (9.7% and 8.1 compared to 6.3% and 6.3%, respectively). A number of other organisms, such as Staphylococcus epidermidis, Streptococcus anginosus, and MRSA (methicillin-resistant Staphylococcus aureus), were present in both groups but in lower numbers overall.
An overview of the characteristics and reasons for preoperative ICU admission and the invasive supports received by the critically ill group of patients is presented in Table 4. The majority of critically ill patients had sepsis with shock and cardiovascular issues (54% and 50%, respectively). A large proportion of patients (77%) required inotropic support, suggesting significant cardiovascular instability and heart failure on admission. Many critically ill patients had respiratory failure, as evidenced by 86% requiring mechanical ventilation on admission. About 34% of the critically ill patients required renal replacement therapy at some point during the admission, highlighting the severity of acute renal failure in this cohort. In regard to the source of critically ill patients prior to admission, most patients were transferred from other ICUs (69%), suggesting high levels of severity and complexity in their care needs.

4. Discussion

Our study offers valuable insights into the characteristics and outcomes of critically and non-critically ill patients who underwent cardiothoracic surgery for infective endocarditis.
The proportions of females among critically ill and non-critically ill patients were 25% and 22%, respectively. These figures are lower than reported in a systematic review of 34 international studies, which reported 32% of patients as females [17]. Additionally, a recent retrospective study in Australia reported that women with IE had a higher risk of death and fewer escalations of care [18]. These gender differences underscore the importance of investigating gender-specific risk factors to tailor prevention and treatment strategies more effectively.
In this study, the critically ill patients with infective endocarditis were younger, with a median of age of 49 years compared to 61 years for the non-critically ill. This finding compares with other Australian studies, which reported a mean age of 50–56 years for patients undergoing cardiac surgery for infective endocarditis [19,20,21]. A separate Australian study conducted between 2000 and 2006 showed an increase in the median age from 60 to 65 years [1]. Similarly, the multinational ICE-PLUS database also reported a median age of 60 years [22]. The variation in median age across studies may highlight the influences of regional healthcare systems and demographics on the management of IE. Perhaps age could also be a component of selection bias, where young patients are offered surgery despite the severity of illness. It is also pertinent to understand that a young age may not necessarily be a risk factor but may also be associated with risky behaviours such as IVDU or predisposing risk factors such as congenital heart disease.
In this study, methicillin-sensitive Staphylococcus aureus (MSSA) was the most common causative organism in both groups but more prevalent in the critically ill patients (66% vs. 27%, p = 0.001). This finding is consistent with data from an Australian-based Queensland Cardiovascular Outcome Registry (QCOR) and an Australian retrospective study by Khan et al., which reported MSSA as the most common organism, at 29% and 59%, respectively [23,24]. Furthermore, an American observational cohort study of 24 intravenous drug users with infective endocarditis also identified MSSA as the predominant pathogen [25]. An understanding of the distribution and local epidemiological trends in IE is crucial for optimising empirical antimicrobial therapy and improving patient outcomes. The limitation of our data is that they do not specify whether the MSSA was healthcare- or community-acquired. Despite a statistically higher association of MSSA bacteria in the critically ill patients, it was not possible to determine causation given the retrospective nature of this study.
The increased prevalence of IVDU among critically ill patients (41%) compared to non-critically ill patients (14%) aligns with trends observed in other studies. This higher incidence of IVDU was associated with a higher rate of right-sided infective endocarditis involving the tricuspid valve in the critically ill cohort. A retrospective American study found that hospitalisations for IE among patients with substance abuse issues increased significantly from 19.9% to 34% (p < 0.0001) [26]. This increase is often attributed to associated heart failure and sepsis. An Australian study reported a 15% overall mortality rate and a 30-day surgical mortality rate of 10% in IVDU patients [27]. The fact that critically ill patients tend to be younger and have a higher prevalence of IVDU suggests a distinct patient subset that may benefit from tailored interventions.
The median time to surgery of 3 days (IQR 1–8 days) for critically ill and 3 days (IQR 1–9 days, p = 0.834) for non-critically ill patients was similar in both groups. This median time to surgery was calculated from the time of cardiac surgical consultation to the time of surgery. The decision about surgical timing is based on a risk–benefit analysis and, unfortunately, the database could not provide these details about the timing of surgery. It is therefore difficult to speculate on the reasoning for this finding. The similar urgency rates (72% vs. 64%, p = 0.45) between the groups suggest that timely decision-making remains a challenge. The timing of surgery for infective endocarditis is critical and has been addressed in various clinical guidelines and consensus statements; however, they do not provide guidance in critically ill patients. The European Society of Cardiology (ESC) guideline classifies surgical indications in IE as emergent (within 24 h), urgent (within a few days), and elective (after 1–2 weeks of antibiotic therapy) [28]. The American Heart Association/American College of Cardiology (AHA/ACC) guideline defines early surgery as occurring during the initial hospitalisation and before completion of a full therapeutic course of antibiotics [29]. Early surgery has been associated with lower in-hospital mortality in IE patients [odds ratio (OR) = 0.57, 95% confidence interval (CI) (0.42, 0.77)] [30]. However, determining the optimal timing for surgery in critically ill patients remains challenging and must balance the risks of delaying intervention against those of early surgery.
The median EuroSCORE II scores for critically ill and non-critically ill patients (2.2 [IQR 1.3–9.8] vs. 3.1 [IQR 1.4–6.1], p = 0.897) suggested comparable baseline surgical risks. However, critically ill patients were more frequently classified in higher-risk categories and had a greater prevalence of NYHA class III/IV symptoms. It is important to note that the EuroSCORE II may not fully capture the complexities associated with critical illness. In a study to validate and compare the EuroSCORE II to another five infective endocarditis-specific risk scores specifically for surgery in IE, its discrimination for 30-day mortality after surgery for IE was higher [31]. The numerous infective endocarditis-specific scores identified in Gatti et al.’s study highlight the complexity of stratification of patients with this condition [31]. More recently, an Italian research group introduced the EndoSCORE, a novel tool designed to predict early (30-day) postoperative mortality, which achieved an AUC of 0.84 [32]. However, due to substantial missing clinical data, we were unable to compare the EndoSCORE with the EuroSCORE II in our patient cohort. Critically ill patients had a significantly higher median ANZROD score compared to non-critically ill patients (0.040 [IQR 0.024–0.090] vs. 0.013 [IQR 0.003–0.038], p = 0.00002), indicating a markedly increased risk of death and greater variability in outcomes. Similarly, the APACHE III score was elevated in the critically ill group (57 [IQR 49–78] vs. 52 [IQR 39–67], p = 0.03), reflecting more severe physiological derangements and comorbidities. Although the difference in APACHE III scores was less pronounced than that observed with ANZROD, it nonetheless supports the classification of these patients as more severely ill.
In this study, the 30-day mortality rates were 13% for the critically ill and 5% for the non-critically ill patients (p = 0.60). Although not statistically significant, both rates were lower than those reported in the current limited literature. For instance, a Finnish study found a 30-day all-cause mortality of 11.3% following admission for infective endocarditis, with mortality rates increasing with age [33]. The lower mortality observed in this study may partially be attributed to the involvement of a multidisciplinary endocarditis team, with careful selection of surgical candidates, which could drive a potential selection bias. While this is a plausible explanation, it remains speculative in the absence of direct supporting evidence. The inherent introduction of bias with the exclusion of patients who did not undergo surgery is acknowledged. The review of those patients is beyond the scope of this paper and will be discussed elsewhere. The absence of key data limits the ability to fully interpret the results and assess the clinical impact of critical illness on these patients.
Critically ill patients had a longer ICU length of stay (LOS), with a median of 5 days [IQR 2–10 days], compared to 2 days [IQR 1–4 days] in the non-critically ill group (p = 0.0002). Although ICU LOS is a common indicator of the ICU outcome, it was controversial in this setting as the critically ill patients were already in the ICU prior to surgery, and hence expected to have a longer LOS. This introduced a confounding factor and bias, which affected the interpretation of the results. To account for the potential bias of preoperative ICU admission, the ICU LOS was also measured from the surgery date to discharge from the ICU, as shown in Table 2. With this adjustment, critically ill patients had a significant longer ICU LOS (6 days [IQR 3–11 days] vs. 3 days [IQR 2–5 days], p = 0.01), indicating a higher acuity and greater need for critical care in these patients postoperatively. Surprisingly, the overall hospital LOS was similar between the two groups (23 days [IQR 14–36] vs. 21 [12–34], p = 0.46). This similar length of stay may be confounded by patients transferred to other facilities or rehabilitation wards. According to the database, the hospital length of stay only accounts for the acute episode of care. Therefore, when patients are transferred to rehabilitation, palliative care, mental health services, or another hospital, it marks the end of the acute care episode. The discharge date is recorded as the date of transfer. Additionally, the data on subsequent care following the transfer are not available in the database. Notably, 26% of critically ill patients underwent elective surgery, suggesting that their procedures were delayed for optimisation or to manage complications, such as the need for neurosurgical interventions. This delay prolonged their ICU stay; however, once stabilised and after surgery, these patients may have had a shorter recovery period on the general ward compared to non-critically ill patients, which may explain the similar overall hospital LOS between the two groups.
Critically ill patients were over three times more likely to receive RRT compared to non-critically ill patients (34% vs. 11%, p = 0.0001). This is an unexpected finding considering that acute renal failure rates were similar in both cohorts at admission to the ICU (9% vs. 5%, p = 0.28). One possible explanation is that critically ill patients may have experienced renal deterioration during their ICU stay, necessitating renal replacement therapy, and were subsequently stabilised before undergoing cardiothoracic surgery. Alternatively, some patients might have already been receiving renal replacement therapy prior to transfer to this ICU and presented with normalised renal function upon admission.
The reoperation rate was comparable between the critically ill and non-critically ill patients (25% vs. 29%, p = 0.81), with reoperations due to bleeding also showing no significant difference (16% vs. 11%, p = 0.74). However, the sample size may be too limited to determine the effect size. These rates exceed the standard 2–7% range typically reported in general cardiac surgeries [34,35,36]. There are currently limited data to explain the higher bleeding and reoperation rates observed in infective endocarditis (IE). A retrospective study of 191 IE patients reported a bleeding rate of up to 10%, with non-survivors experiencing rates as high as 33% [37]. Additionally, a single-centre study found that IE patients had significantly more bleeding complications, as measured by the perioperative bleeding score (odds ratio 3.0, p=0.018), and a higher rate of re-exploration [38]. Another study reported postoperative bleeding in 26% of IE patients, with 96% requiring blood transfusions [39]. The higher bleeding rates in IE patients may be attributed to coagulopathy and platelet dysfunction. The intensive care has had a blood management team utilising point-of-care coagulation testing (Multiplate® and ROTEM®) since 2012. This practice has reduced transfusion in cardiac surgery, in general, and has allowed targeted transfusions. A well-designed prospective trial could provide deeper insights into this bleeding observation.
The retrospective nature of this study and its conduct at a single tertiary cardiothoracic centre in Australia limit the generalisability of the results to other settings with different patient populations, clinical practices, and resource availability. The absence of a universally accepted definition for “critical illness” may have introduced classification bias. In this study, critical illness was pragmatically defined as ICU admission prior to cardiac surgery, which may not fully capture the clinical complexity or severity of all patients. Patients with infective endocarditis who were critically ill but did not undergo surgery were excluded. This may have introduced selection bias and limited the ability to fully assess the impact of critical illness across the entire spectrum of disease severity. The accuracy and validity of the findings are inherently dependent on the quality of the databases used. Variability in data entry practices and potential misclassification may have affected data integrity. ICU length of stay (LOS), while commonly used as an outcome measure may not have been an appropriate outcome measure in this context as it introduced bias. The definition of acute renal failure used in the ANZICS-APD is not standardised or universally accepted, which may limit the comparability of this outcome with other studies. This study only assessed outcomes up to hospital discharge. Long-term outcomes such as survival, quality of life, and functional recovery were not captured, limiting the ability to evaluate the broader impact of critical illness.
As with many large clinical databases, missing or incomplete data may have compromised the representativeness and reliability of the findings [40]. Additionally, key variables relevant to patient-centred outcomes such as quality of life, functional status, and prognosis were not available.
These limitations highlight the broader challenges in designing and maintaining clinical registries, particularly the need for standardised definitions, comprehensive data collection, and long-term follow-up to support meaningful research and patient care improvements.
Despite limitations such as a relatively small sample size and missing data, this study provides valuable insights into the characteristics and outcomes of critically ill patients with IE undergoing cardiothoracic surgery. Given the rarity of IE and the even smaller subset of patients requiring preoperative intensive care, this study represents a unique and significant contribution—one of the largest known single-cohort analyses focused specifically on this high-risk population.
Importantly, critical illness is not currently addressed in existing clinical guidelines for the management of IE. Yet, these patients often pose complex challenges regarding surgical decision-making, optimal timing of intervention, and prognostication. By identifying key factors associated with mortality and adverse outcomes, this study lays the groundwork for future prospective studies and hypothesis-driven interventional research. For example, the observed increase in bleeding complications among critically ill patients with IE warrants further investigation. A prospective study could explore the underlying mechanisms, such as coagulopathy, anticoagulation strategies, or surgical complexity, that may contribute to this finding.
Moreover, this study highlights the need for more comprehensive data collection. The identification of missing but clinically relevant variables such as long-term outcomes, quality of life, and functional recovery underscores the importance of developing a dedicated registry for infective endocarditis. Such a registry could enhance understanding, support evidence-based decision-making, and ultimately improve patient care.

5. Conclusions

In patients undergoing cardiothoracic surgery for infective endocarditis, critical illness was associated with high illness severity scores (APACHE III-J and ANZROD), a longer ICU LOS, and the need for renal replacement therapy but did not significantly influence 30-day mortality rates, EuroSCORE II predictions, reoperation rates for bleeding, or hospital length of stay. Despite the study limitations, the findings offer valuable insights that inform the development of dedicated registries for infective endocarditis capturing both clinical and patient-centred outcomes.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/hearts6020015/s1, Table S1: All organisms.

Author Contributions

Conceptualisation, M.P.M., K.R.V., R.H., N.G.O. and M.R.; methodology, M.P.M., J.F.S. and N.G.O.; validation, M.P.M., L.M. and N.G.O.; formal analysis, N.G.O.; data curation, all authors; writing—original draft preparation, M.P.M.; writing—review and editing, all authors; supervision, N.G.O. and M.R.; funding acquisition, M.P.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received funding from The Prince Charles Hospital Foundation NI2019-42 (MPM).

Institutional Review Board Statement

IRB approval for the conduct of this study was obtained from the Metro North Hospital and Health Services Human Research Ethics Committee (approval number: HREC/2024/MNHA/111882, approval date: 20 March 2025).

Informed Consent Statement

Patient consent was waived by the IRB as this study met all requirements for waiver of consent stipulated by the local regulatory authority.

Data Availability Statement

Data cannot be shared publicly due to institutional ethics, privacy, and confidentiality regulations. Data released for research under Sect. 280 of the Public Health Act 2005 require an application to the Director-General of Queensland Health (PHA@health.qld.gov.au).

Acknowledgments

The authors wish to thank Chantal Kelly and Rachell Bushel (Data Managers from the Cardiothoracic Surgery and Intensive Care Units) for their assistance.

Conflicts of Interest

The authors declare no conflicts of interest.

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Table 1. Patient characteristics.
Table 1. Patient characteristics.
Critically IllNon-Critically Illp-Value
n = 32n = 310
Gender
·         Female, n (%) 8 (25)69 (22)0.85
Age (years), median (IQR) 49 (42–56)61 (44–70)0.006
Age groups (years)
·         ≤29, n (%) 3 (9)22 (7)0.9
·         30–59, n (%) 22 (69)128 (41)0.02
·         ≥60, n (%) 7 (22)160 (52)0.12
Intravenous drug use (IVDU) history
·         Yes, n (%) 13 (41)43 (14)0.03
·         No, n (%) 15 (47)192 (62)0.25
·         Unknown, n (%) 4 (13)75 (24)0.61
APACHE III-J, median (IQR)57 (49–78)52 (39–67)0.03
ANZROD, median (IQR)0.04 (0.024–0.090)0.013 (0.004–0.038)0.00002
EuroSCORE II, median (IQR) 2.1 (1.3–10)2.8 (1.3–5.7)0.69
EuroSCORE II (risk)
·         Low (≤4), n (%) 20 (63)194 (63)1.00
·         Medium (>4 <8), n (%) 2 (6)60 (19)0.64
·         High (≥8), n (%) 10 (31)56 (18)0.34
Acute renal failure, n (%)3 (9)15 (5)0.28
Left ventricular function (ejection fraction %)
·         Normal (>50%) 23 (72)259 (84)0.14
·         Mild dysfunction (40–49%) 3 (9)34 (11)0.92
·         Moderate dysfunction (30–39%) 4 (13)12 (4)0.52
·         Severe dysfunction (<30%) 2 (6)5 (1)0.7
NYHA classification before admission
·        NYHA I, n (%) 10 (32)100 (32)1.00
·        NYHA II, n (%) 9 (29)135 (44)0.38
·        NYHA III, n (%) 10 (32)71 (23)0.53
·        NYHA IV, n (%) 2 (7)4 (1)0.69
Type 2 diabetes, n (%)5 (16)57 (19)0.87
Surgery classification
·         Emergency, n (%) 2 (6)8 (3)0.84
·         Urgent, n (%) 23 (72)198 (64)0.45
·         Elective, n (%) 7 (22)104 (34)0.51
Time to surgery (days), median (IQR) 3.5 (1.5–8)3 (1–9)0.98
Active infective endocarditis, n (%)30 (94)255 (82)0.10
Site for infection by nature of valve
·         Native valve31 (97)285 (92)0.32
·         Prosthetic valve 1 (3)25 (8)-
Site of infection by valve
·         Aortic valve only10 (32)110 (35)0.85
·         Mitral valve only5 (16)94 (30)0.50
·         Aortic valve + aortic root 3 (10)36 (12)0.92
·         Aortic valve + mitral valve3 (10)19 (6)0.80
·         Tricuspid valve only3 (10)16 (5)0.74
·         Other (all other combinations)7 (22)36 (12)0.48
APACHE III-J: Acute Physiology and Chronic Health Evaluation (APACHE) III-J, ANZROD: Australian and New Zealand Risk of Death, NYHA: New York Health Association.
Table 2. Outcomes of patients with infective endocarditis.
Table 2. Outcomes of patients with infective endocarditis.
Critically Ill (n = 32)Non-Critically Ill (n = 310)p-Value
Mortality (30 days), n (%)4 (13)16 (5)0.60
Length of stay in days (LOSd)
·           ICU LOSd, median (IQR)5 (2–10)2 (1–4)0.0004
·           ICU LOSd (surgery *), median (IQR)6 (3–11)3 (2–5)0.001
·           Hospital LOSd, median (IQR)23 (14–36)21 (12–34)0.46
Renal replacement therapy11 (34)33 (11)0.0001
Reoperation, n (%)8 (25)89 (29)0.81
Reoperation for bleeding, n (%)5 (16)35 (11)0.74
* LOS from surgery date to ICU discharge.
Table 3. Organisms causing infective endocarditis.
Table 3. Organisms causing infective endocarditis.
OrganismCritically Ill (n = 32)Non-Critically Ill (n = 310)p-Value
MSSA (methicillin-susceptible Staphylococcus aureus)21 (66%)82 (27%)p = 0.001
MRSA (methicillin-resistant Staphylococcus aureus)2 (6.3%)8 (2.6%)
Enterococcus faecalis2 (6.3%)30 (9.7%)
Staphylococcus lugdunensis1 (3.1%)6 (1.9%)
Staphylococcus epidermidis1 (3.1%)17 (5.5%)
Streptococcus mitis2 (6.3%)25 (8.1%)
Streptococcus sanguinis1 (3.1%)17 (5.5%)
Streptococcus mutans0 (0%)9 (2.9%)
Streptococcus salivarius0 (0%)3 (1.0%)
Streptococcus agalactiae0 (0%)12 (3.9%)
Streptococcus anginosus1 (3.1%)7 (2.3%)
Streptococcus gordonii0 (0%)6 (1.9%)
Haemophilus parainfluenzae0 (0%)6 (1.9%)
Propionibacterium acnes0 (0%)4 (1.3%)
Others (2 or fewer cases each)0 (0%)38 (12.3%)
Culture negative1 (3.1%)40 (12.9%)
Table 4. Characteristics of patients admitted to intensive care unit.
Table 4. Characteristics of patients admitted to intensive care unit.
Characteristicsn (%)
ICU admission diagnosis (APACHE III-J)
  •Sepsis with shock other than urinary (501)16 (54)
  •Cardiovascular (101–111)16 (50)
Invasive therapies
  •Inotropes27 (77)
  •Renal replacement therapy11 (34)
  •Mechanical ventilation30 (86)
Patient admission source to ICU
  •Ward7 (20)
  •Other hospital ICU24 (69)
  •Emergency department4 (11)
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Matebele, M.P.; Vemuri, K.R.; Sedgwick, J.F.; Marshall, L.; Horvath, R.; Obonyo, N.G.; Ramanan, M. The Impact of Critical Illness on the Outcomes of Cardiac Surgery in Patients with Acute Infective Endocarditis. Hearts 2025, 6, 15. https://doi.org/10.3390/hearts6020015

AMA Style

Matebele MP, Vemuri KR, Sedgwick JF, Marshall L, Horvath R, Obonyo NG, Ramanan M. The Impact of Critical Illness on the Outcomes of Cardiac Surgery in Patients with Acute Infective Endocarditis. Hearts. 2025; 6(2):15. https://doi.org/10.3390/hearts6020015

Chicago/Turabian Style

Matebele, Mbakise P., Kanthi R. Vemuri, John F. Sedgwick, Lachlan Marshall, Robert Horvath, Nchafatso G. Obonyo, and Mahesh Ramanan. 2025. "The Impact of Critical Illness on the Outcomes of Cardiac Surgery in Patients with Acute Infective Endocarditis" Hearts 6, no. 2: 15. https://doi.org/10.3390/hearts6020015

APA Style

Matebele, M. P., Vemuri, K. R., Sedgwick, J. F., Marshall, L., Horvath, R., Obonyo, N. G., & Ramanan, M. (2025). The Impact of Critical Illness on the Outcomes of Cardiac Surgery in Patients with Acute Infective Endocarditis. Hearts, 6(2), 15. https://doi.org/10.3390/hearts6020015

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