Cardiovascular diseases, including coronary heart disease, heart failure, and cerebrovascular disease, constitute leading causes of cardiovascular morbidity and mortality worldwide.¹ Great advances in cardiovascular prevention and management^2–4 have dramatically altered the outcome of these patients. Still, this trend has not been homogeneous between men and women. In the last decades, a growing awareness of the similarities and differences between men and women regarding cardiovascular function, disease burden, and epidemiology has been noted. Several initiatives issued by scientific societies have increasingly recognized the need for reducing the gender gap in clinical care and research.⁵ Various publications have highlighted the impact of gender on several fields of cardiology such as coronary artery disease^6–8 or heart failure,^9,10 as well as in general medicine involving sepsis¹¹ or pneumonia.⁹

Infective endocarditis (IE) constitutes a rare condition with significant morbidity and mortality. Demographic changes, with an aging population associated with an upward trend in the implantation of prosthetic cardiac valves and cardiac devices, have justified a similar trend in the incidence of this pathology.^12–14

The impact of gender in the clinical profile and outcome of patients with IE has been seldom approached. A higher incidence among men has been noted^15,16 in international registries. Moreover, a recent systematic review of observational series from Portugal¹⁷ concluded that a higher prevalence of men was noted in all studies and this predominance was also noted in all surgical series (men constituted more than two-thirds of all operated patients). Still, scarce and conflicting evidence persists regarding the influence of gender on the access to cardiac surgery and fatal outcome,^18–24 being mostly based on single-center cohorts. Populational studies addressing this issue are rare,²³ yet crucial to avoid selection bias in observational studies performed in tertiary centers.

Therefore, using population-based data, the authors sought to explore the association of gender and the clinical profile of patients hospitalized with IE, access to surgical interventions, and clinical outcomes.

In a contemporary populational cohort of patients hospitalized with IE in Portugal and after controlling for several risk factors, important differences were noted between women and men. Men were more prevalent, being younger and with a higher rate of comorbidities. On the other hand, women were less likely to undergo cardiac surgery during the incident hospitalization for IE, with a higher post-operative mortality rate. Even so, overall in-hospital mortality was comparable among men and women.

Our data showed a 1.3 man/woman ratio, which is in accordance with a higher prevalence of IE in men in populational studies.^12–14 The reasons for this remain speculative, but factors such as a higher valve disease prevalence in men and different hormone profiles have been previously mentioned.¹⁹ Women were older but men presented a higher burden of comorbid conditions such as coronary artery disease, cardiac valve disease, liver failure, or malignancy. Infectious agents such as Staphylococcus, Streptococcus, or Enterococcus were more common in men whereas women presented a higher rate of Gram-negative agents. In-hospital complications were analogous, with women presenting a higher rate of acute heart failure while men had a higher rate of acute renal failure and sepsis. All these aspects were noted in previous gender-based studies.^18,21,23

The male/female ratio increased to 3.0 in the surgical subgroup. Indeed, women were less likely to undergo cardiac surgery, which is a common finding with other studies.^{23,19,21,23,26} Nonetheless, general indications for performing cardiac surgery in the context of IE²⁷ include acute heart failure, uncontrolled infection, and embolism. In this cohort, the profile of in-hospital-related complications was comparable between men and women, the latter group presenting a higher incidence of heart failure; this fails to explain the gender disparity in the access to surgical treatment among patients with IE. Additionally, men presented a higher incidence of hemorrhagic stroke, which normally delays and sometimes excludes cardiac interventions. Physician awareness²⁸ and other comorbidities not taken into account in this study such as frailty score,²⁹ dementia,³⁰ or neurologic sequelae could also have contributed individually to the decision to perform cardiac surgery and should be considered. Age, female gender, and endocarditis are variables included in cardiac surgery risk stratification scores such as EUROSCORE³¹ or the STS³² and the fact that women were older could have precluded cardiac surgery.

Additionally, women who underwent surgery in our study had a higher rate of fatal outcome when compared to men and constituted an independent risk factor for postoperative mortality. Demographics, comorbidities, infectious agents, and in-hospital-related complications in this surgical cohort were similar between men and women. This real-world data validates the increased surgical risk in women with IE, which is already considered in the above-mentioned risk scores. The higher surgical susceptibility of women was also found by Curlier et al.²³ and in a recent meta-analysis by Varela et al.³³ Weber et al.²² concluded that a higher postoperative mortality rate in women was due to the presence of more comorbidities and perioperative risk factors, which was apparently not the case in the current study. This higher mortality after surgery in the female sex was also noted in other fields of cardiac surgery, such as after coronary artery bypass graft surgery.³⁴ Older age, a lower body surface area,³⁵ a higher incidence of heart failure, and referral bias²¹ could also partially justify this higher surgical susceptibility.

Finally, regarding in-hospital mortality, no significant differences were noted between men and women. This is similar to findings from Curlier et al.²³ It would be critical to analyze the causes of death in these patients. Actually, a recent study based on national death certificate data in Portugal³⁶ concluded that, in a cohort whose basic cause of death was IE, women presented a 19% higher death rate than men. Conversely, Thuny et al.³⁷ concluded that a high burden of comorbidities and aortic valve involvement may explain an increased death rate among women.

In our study, women differed from men in significant aspects of clinical presentation and treatment options. They were older and less likely to undergo cardiac surgery when hospitalized with IE, despite presenting less comorbid conditions and a comparable complication rate. Higher postoperative mortality, but not overall in-hospital mortality, was observed. Further research is needed to understand reasons that can explain individualized management strategies and the impact of surgery on survival in women hospitalized with IE.

Our study has several limitations. First, ICD-9 and ICD-10 codes were used to identify individual cases of IE and clinical variables on an administrative database. The authors were unable to consult the patient’s electronic database to confirm the diagnosis and to identify other important variables. Therefore, diagnosis or coding errors could have occurred. Second, the authors were unable to trace patients beyond the index hospitalization and cardiac surgery could have been performed after discharge. This could lead to an underestimation of the number of cardiac surgeries performed in this cohort. Therefore, only in-hospital surgical management during the index hospitalization was assessed. Third, this is a populational study; management strategies by individual physicians and the patients’ personal treatment options could thus eventually lead to a referral bias towards cardiac surgery. Fourth, variables such as microbiological subgroups, source of bacteremia (community vs healthcare-related), presence of dementia, frailty score, or a socioeconomic situation that could have further explained our findings were not available for analysis.

In Portugal between 2010 and 2018, hospitalization with IE occurred less frequently in women, who were older and presented fewer comorbidities. A comparable rate of in-hospital complications was observed, with a higher prevalence of acute heart failure. Regarding surgical treatment, women were less likely to undergo cardiac surgery and female gender was an independent predictor of postoperative mortality. Further research is warranted to understand the reasons behind the influence of gender on treatments and outcomes of this disease. The individualized management of IE is frequently challenging, and the influence of gender should be carefully considered together with comorbidities and complications to improve the outcome of these patients.