The 2009 and 2015 ESC guidelines1,2 introduced a contemporary approach to the role of surgery during the active phase of infective endocarditis (IE) and nowadays early surgical intervention is standardized. Complementary surgical intervention occurs in 15–50% of overall cohorts -in registries such as EURO-ENDO3 or ICE,4 almost half the patients had surgery, being higher in Europe than in the rest of the world.5

Additionally, it is estimated that less than half of the patients who have an indication for surgery during IE treatment are submitted to surgery.6,7

Retrospective unicenter observational studies and expert input constitute the majority of worldwide published evidence3 on surgery in the context of IE. In fact, randomized clinical trials and metanalyses are scarce in the field of IE. In a multicentric registry in Spain, Revilla et al.8 have identified heart failure and uncontrolled infection as the main reasons to undergo urgent surgery, with the latter and renal failure as important predictors of a fatal outcome.

Information derived from nationwide studies is crucial to understand the full impact of surgical intervention on the outcome of such an uncommon disease, avoiding the selection bias inherent to all published observational studies from tertiary hospital centers.

Therefore, using populational-based data, we aimed to characterize the clinical profile of patients hospitalized with IE and submitted to cardiac valve surgery and to identify factors associated with in-hospital mortality.

This contemporary nationwide analysis of 937 patients hospitalized with IE and submitted to cardiac surgery in the public hospital network in Portugal assessed demographics, medical background, microbiology and clinically relevant outcomes such as all cause in hospital mortality. Three quarters of patients were men, most in the 4th to 7th decade of life, with a significant prevalence of structural valve disease. Factors associated with in-hospital surgical management included male sex, age younger than 60 years old, with few comorbidities, the presence of previous cardiac valve disease, Streptococcus spp infection, heart failure, acute renal failure, and systemic embolism. Finally, 85% of patients survived until hospital discharge. Female patients, patients with previous coronary, renal, or liver chronic disease, cardiac valve prosthesis, infection with Staphylococcus spp, acute renal failure, and the presence of sepsis had higher odds of in-hospital mortality.

In our study, patients that underwent cardiac surgery had a similar profile to other international series.10,11 The average age of surgically managed patients was 61.1 years old, and 85.1% were between 40 and 79 years old. Elderly patients (≥ 80) rarely underwent surgery in the context of IE which is comparable to the findings in the recently published Swedish registry by Ragnarsson et al.12 Advanced age is related to worse outcomes in cardiac surgery even though the threshold for intervention is shifting towards sicker and more elderly patients, particularly in the elective field. In IE, the frequent indication for urgent surgery and patient's clinical instability makes this assessment more challenging. Aging is also linked to a higher rate of comorbidities. Even though our data did not allow for the estimation of the Charlson score, a score that evaluates the 10 year prognosis in patients with multiple comorbidities, we can appreciate that the burden of comorbidities was lesser in the surgically managed cohort. This is also a common finding in other registries such as the Euro-Heart Survey.13 Heart valve disease was also a predominant finding in our study, as was the case for the large multicentric registry GAMES.14

Patients treated with surgery were predominantly men. In fact, gender impact in the access to cardiac surgery overall is still quite controversial. Varela et al.15 also concluded that women were less likely to undergo cardiac surgery in the context of IE. Female gender is a current variable predicting increased risk in most stratification risk scores for cardiac surgery such as EUROSCORE I16 and II17 or the specifically IE related PALSUSE14 risk score which may therefore lead to a selection bias in the access to cardiac surgery in the context of IE.

The surgical rate presented in this analysis was lower than reported by Portuguese cross-sectional single-center institutions18 (29.8% on average), matching other European populational series such as Sunder et al.19 (in France) or Shah et al.20 (in Scotland) nonetheless. Reasons explaining this discrepancy between populational and registries/single-center observational series may lie on national global access to cardiac surgery (tertiary versus community hospital differences, the formers with a higher number of cross-sectional studies published), physicians’ awareness, and selection bias. In addition, postponing surgery in IE patients to the ambulatory settings was not assessed in our analysis, which could also have contributed to a lower than the expected surgical rate in this analysis.

Worldwide, access to cardiac surgery is not homogeneous between different regions.21 Cabell et al.22 were the first to acknowledge that geographical location was a strong predictor of IE outcome, even after adjusting for other patient-specific variables. Health care access, different practices, and referral pathways were identified as relevant factors. The EURO-endo registry23 concluded that patients hospitalized with IE in European centers were more likely to undergo surgery. In Portugal, the National Health System delivers global health care and access to all Portuguese citizens. Still, the distribution of health care and human resources is diverse.24 Araújo et al.25 have shown existing inequalities in coronary heart disease mortality in different Portuguese regions. Healthcare-related factors such as distribution and access to services and patterns of use/referral could significantly impact coronary heart disease's outcome. Probably these aspects are also relevant regarding IE surgical management. There are 6 Portuguese public centers of cardiac surgery – 2 in the Oporto area, 1 in Coimbra, and 3 in Lisbon, the most industrial and crowded regions.26 In our study, less than half the patients were admitted to the previously mentioned tertiary hospitals firsthand. Still, being first admitted in a hospital with cardiac surgery on-site was associated with surgical management, even after correction for other clinical variables. Additionally, patients presented fewer comorbidities and had a lower rate of complications than those from non-surgical hospitals. Inadequate referral pathways and physician's noncompliance to scientific guidelines are among the reasons that can partially explain these findings.

In our study, nearly three quarters of the total cohort underwent single valve surgical intervention as in most other surgical series.27 The aortic valve was the most frequently involved, with replacement being performed in nearly all situations. Regarding mitral valve repair, it was performed in 30% of cases. In fact, the more recent guidelines2,28 have been defending mitral repair as the first option whenever feasible. In this context, published series have evaluated mitral valve intervention in this context report repair ranging between 21–80% of cases.29–35 Populational series, namely Lee et al.34 (from Taiwan) and Toyoda et al.35 (USA), report values inferior to our findings (21.2% and 22%, respectively). Overall, significant heterogeneity among centers and series is noted, probably related to the individual complexity of cases and the technical expertise in relation to the volume of cases.2 Our study is focused on immediate postoperative outcomes, not providing data on the clinical and imagiological follow-up of patients. Neverthesless, we acknowledge that assessing the effectiveness of these interventions in IE through lifelong surveillance is indeed of paramount importance.

Patients submitted to cardiac surgery presented a lower in-hospital mortality rate when compared to exclusively medically managed patients. The protective role of cardiac surgery has been acknowledged in several cross-sectional studies,36–39 in registries such as the International Collaboration on Endocarditis – Prospective Cohort Study (ICE-PCS)39 and in a metanalysis published in 2011.40 Additionally, high risk patients are the ones that benefit the most from surgical intervention.41 Nevertheless, a better clinical profile of the patients submitted to surgery is noted in our study which can be a translation of an inherent selection bias ultimately contributing to a more favorable outcome.

The all-cause mortality rate among surgically managed patients was similar to that observed in cross-sectional observational single centers18 in Portugal (ranging from 13% to 16%). After stepwise logistic regression, 7 factors were associated with a fatal outcome: female gender, cardiac valve prosthesis, previous chronic coronary, kidney, or liver disease, and the presence of acute renal failure or sepsis. Apart from liver disease, all the remaining factors are included in the general surgical risk stratification scores previously mentioned, particularly EuroSCORE I and II, already validated in a Portuguese surgical center.42 In fact, those are non specific prognostic markers in surgically managed patients. We identified 4 variables included in the PALSUSE score41 such as age, female gender, prothesis heart valve and Staphylococcus spp infection. An Italian registry published by De Feo et al.43 also identified renal failure as a significant prognostic marker. The presence of previous liver disease usually puts patients at the highest risk, being denied surgery globally. Our data does not allow for the analysis of IE specific markers such as physical signs at presentation, intracardiac destruction or vegetation size which could also play a relevant role in the final outcome of these patients as was documented in a recent brasilian cohort analysis44 or in the IE specific risk score PALSUSE.14

Our analysis provides an exceptional insight into the characterization and prognosis of patients hospitalized with IE and submitted to cardiac surgery assembling data from most public hospitals of the National Health System in Portugal, regardless of their complexity level. Future research may rely on prospective assessment of patient risk stratification considering IE specific markers, impact of negative blood cultures, geographical location, timing to intervention, effectiveness of valve repair in IE, and the need to reintervention.

First, it is an analysis based on administrative data originated from discharge medical reports. Confirmation of the data, diagnosis, and ICD coding was not possible. Nevertheless, well-trained physicians are responsible for the discharge medical report and its coding, which can reduce the impact of errors. Additionally, high volume administrative databases allow the analysis of large sample sizes obtained over time and robust power even for very rare events.45 In healthcare, it can be especially useful when the object of study is a specific event like hospitalization for IE or a procedure such as cardiac valve surgery,46 as was our case.

Second, identifying the patients with a precise surgical indication not submitted to surgery was not accessible, and therefore an inherent selection bias may be present in this analysis.

Third, a complete analysis of patients operated after discharge in an elective setting was not accessible, possibly leading to underestimating patients submitted to surgery. Therefore, our study is limited to in-hospital surgical intervention in the index hospitalization.

Fourth, as this is based on discharge medical report information, no data were obtained regarding surgery's timing, the urgency, and technical details regarding the surgery, which could also influence these patients’ outcomes.

Finally, confounders not evaluated in the database cannot be excluded.

Cardiac surgery in IE was performed in younger patients, mostly men with few comorbidities. Clinical complications, namely heart failure and systemic embolism, were also associated with cardiac surgery. Finally, female sex, chronic diseases, valve prosthesis, and a clinical course complicated by acute renal failure and sepsis were associated with a fatal outcome (Fig. 2), factors considered in conventional general surgical risk scores such as EuroSCORE. Early identification of stratification markers that may influence the overall prognosis in IE is crucial in the real world clinical setting.

Fig. 2.

Main findings and take-home message of the current study.

(0.32MB).

This study has not received any public or private funding.

Conceptualization: C. Sousa; F.J. Pinto. Data curation: C. Sousa; P.J. Nogueira. Formal analysis: C. Sousa; P.J. Nogueira. Funding acquisition: A. Nobre. Investigation: C. Sousa; P.J. Nogueira; RF; A. Nobre; F.J. Pinto. Methodology: C. Sousa; P.J. Nogueira. Project administration: C. Sousa; F.J. Pinto. Resources: C. Sousa; P.J. Nogueira. Software: C. Sousa; P.J. Nogueira. Supervision: P.J. Nogueira; A. Nobre; F.J. Pinto. Validation: P.J. Nogueira; R. Ferreira; A. Nobre; F.J. Pinto. Visualization: C. Sousa. Writing – original draft: C. Sousa. Writing, review, and editing: P.J. Nogueira; R. Ferreira; A. Nobre; F.J. Pinto.

None declared.