Infective endocarditis (IE) remains a life-threatening condition characterized by infection of the endocardial surface of the heart, often leading to severe complications including acute heart failure (AHF), systemic embolization, and uncontrolled infection [1, 2, 3]. Globally, the reported in-hospital mortality rates for IE vary widely, ranging from 15% to 50% [4, 5, 6, 7, 8, 9, 10, 11]. This likely reflects heterogeneity in patient populations, pathogen profiles, and healthcare infrastructure.

The diagnostic approach to IE has evolved substantially in recent years. The 2023 European Society of Cardiology (ESC) guidelines for the management of IE now integrate advanced imaging modalities into the diagnostic algorithm, including ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography and cardiac computed tomography angiography [12]. These modalities have improved the detection of perivalvular complications and embolic events, particularly in patients with prosthetic valves or intracardiac devices. Concurrently, the 2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) criteria have expanded the diagnostic framework by incorporating these advanced imaging findings, newer microbiological techniques, and updated histopathological definitions, thereby improving diagnostic sensitivity and specificity [13].

Previous studies have consistently identified several independent predictors of in-hospital mortality in patients with IE, including older age [5, 14, 15], prior stroke [10], septic shock [11, 14, 16], heart failure (HF) [5, 8, 11, 16], acute kidney injury (AKI) [5], cerebrovascular complications [5, 17], embolic complications [18, 19], prosthetic valve endocarditis (PVE) [19], and the absence of early surgery in patients with established surgical indications [5, 16]. However, most of this evidence originates from high-income countries with timely access to advanced diagnostics, multidisciplinary endocarditis teams, and early surgical intervention. These findings may not be directly applicable to resource-limited and war-affected settings, where delayed presentation, limited microbiological yield, constrained intensive care capacity, and restricted access to cardiac surgery are common. In such environments, patients often present with advanced disease and severe systemic complications, potentially modifying the relative impact of traditional prognostic factors on in-hospital mortality.

Yemen has been affected by a prolonged armed conflict since late 2014, with a marked escalation following the onset of regional military intervention in early 2015. Over more than a decade, this conflict has led to widespread destruction of healthcare infrastructure, shortages of medical supplies and trained personnel, and major disruptions in referral networks and continuity of care. Access to advanced diagnostic modalities, intensive care services, and cardiac surgery has become severely constrained, while delays in seeking medical attention have become common due to insecurity and socioeconomic collapse. These conditions have profoundly influenced the clinical presentation, management, and outcomes of severe infections such as IE, underscoring the need for context-specific evidence from war-affected, resource-limited settings. Therefore, the aim of this study was to identify independent predictors of in-hospital mortality among patients hospitalized with IE at Yemen’s largest tertiary referral center, with particular emphasis on clinically actionable factors relevant to resource-limited, war-affected healthcare settings.

Of the 60 patients included in this study, 17 died during hospitalization, yielding an in-hospital mortality rate of 28.3%.

In this cohort of patients with IE admitted to a tertiary referral center in Yemen, septic shock and AKI emerged as the only independent predictors of in-hospital mortality. Both variables reflect advanced systemic involvement and multiorgan dysfunction, underscoring that short-term mortality in this setting is primarily driven by the severity of acute complications rather than baseline demographic or echocardiographic characteristics. Notably, traditional baseline variables did not retain independent prognostic significance after adjustment, highlighting the central role of organ failure and uncontrolled systemic inflammation in determining early outcomes.

In recent decades, the epidemiological profile of IE has undergone a significant shift, driven by evolving patient demographics and the emergence of new risk factors [27]. When compared with international data, important distinctions emerge. Patients in this cohort were considerably younger, with a mean age of just over 34 years, and RHD was the predominant underlying condition. This contrasts sharply with reports from high-income countries, where IE typically affects older individuals with degenerative valve disease, PVE, or device-related infections [5, 11, 15, 28]. Similar trends of younger age and RHD predominance have been described in studies from sub-Saharan Africa, such as Ethiopia and Egypt [7, 29], underscoring the ongoing burden of preventable structural heart disease in these regions. Moreover, regional variations in demographic and clinical profiles should be considered when interpreting and comparing epidemiological data for IE. The male predominance observed in our cohort is also in line with previous studies [6, 19, 30], while the high proportion of patients from rural areas highlights disparities in healthcare access and delayed presentation.

Blood culture positivity is one of the major diagnostic criteria for IE. Nevertheless, failure to isolate the causative microorganism may occur due to infection with nonbacterial or fastidious pathogens, suboptimal sampling or culture techniques, limitations of automated detection systems, or prior administration of antimicrobial agents before obtaining blood cultures [31, 32]. We documented culture-negative IE in 68.3% of patients. This proportion is higher than that reported in Jordan, Qatar, and Egypt [28, 29, 30], but lower than that reported in Ethiopia [7]. Similarly, a previous study from Yemen reported culture-negative IE in 94% of cases [6]. The markedly higher proportion in that study was likely attributable to the fact that all patients had been on antibiotic therapy for at least four days before admission. The notably low rate of microbiological detection in our cohort can be plausibly attributed to two interrelated factors. First, a considerable proportion of patients (73.3%) had received antibiotic therapy before admission. This is a well-known factor in the literature for significantly reducing the diagnostic yield of blood cultures in IE. Second, as a tertiary referral center, our institution receives patients transferred from peripheral healthcare facilities where empiric antibiotic regimens are often initiated to stabilize the patient’s condition before referral. Importantly, data on whether blood cultures were performed at the referring hospitals before transfer were not systematically available. Even when the data was obtained, results rarely accompanied the patient due to fragmented communication between facilities. This lack of coordination further compounds the diagnostic challenge and limits our ability to ascertain the true microbiological profile of IE in this setting. The combination of prior antimicrobial exposure, referral-related delays, and incomplete interfacility communication is likely to explain the disproportionately high prevalence of culture-negative IE observed in our study. Accordingly, these factors should be carefully considered when interpreting our findings and when drawing comparisons with reports from other regions.

The complications of IE can be broadly categorized into three major groups. The first group includes cardiac complications, such as worsening myocardial infarction or HF. The second group involves the deterioration of non-cardiac organ function and pre-existing comorbidities, including AKI, stroke, DM, and chronic obstructive pulmonary disease. The third group encompasses complications requiring intensive care management, such as sepsis, invasive mechanical ventilation, and dialysis [33]. Patients frequently develop these complications as a consequence of delayed diagnosis and late presentation to the hospital [5, 34]. Previous studies have reported that approximately 80% of patients with IE experience at least one of these complications during the disease course [35, 36]. It has also been reported that major complications were observed in 32.4% of patients at admission, rising to approximately 86% during hospitalization. This highlights the progression of disease before presentation, as well as the critical need for close monitoring and early intervention to prevent further deterioration [35]. Our cohort demonstrated an even higher overall complication rate of 90%, which is among the highest reported to date and substantially exceeds that reported in Jordan (65.2%) and Ethiopia (75.9%) [7, 30]. Cases in Yemen frequently present late and also experience delays in receiving surgical intervention, underscoring the critical need for early diagnosis, timely referral, and prompt management to reduce adverse outcomes. Moreover, the markedly low rate of surgical management within our cohort may have further contributed to the high prevalence of complications.

Surgical intervention was indicated in 92% of our cohort, reflecting the advanced clinical stage at presentation. However, only 33% of those with a surgical indication actually underwent surgery. This rate is comparable to that reported in Saudi Arabia (27%) and Egypt (28%) [28, 37], but substantially lower than in Belgium (56%) [38], and markedly lower than the 50% reported previously in Yemen [6]. This gap between indication and intervention is a critical finding; failure to operate on such a high proportion of indicated patients may partially explain the progression to septic shock (17%) and AKI (31.7%) observed in our cohort, as these complications may have been mitigated by timely surgical source control. Among the 55 patients with a surgical indication, only 18 (32.7%) ultimately underwent surgery. No statistically significant association was observed between surgical intervention and in-hospital mortality (COR 0.801; 95% CIs: 0.232–2.769; p = 0.726). This finding should be interpreted with caution, given the small sample size and the observational nature of our study. Patients who underwent surgery may have been systematically different from those who did not (e.g., potentially younger, more hemodynamically stable, or with fewer comorbidities), but the ability to adjust for these differences was limited by the small number of outcome events. Furthermore, patients who deteriorated rapidly and died before surgery were inevitably classified in the non-operated group, introducing a survival bias that may underestimate the potential benefit of surgery. The discrepancy between indication and intervention is largely driven by late clinical presentation and systemic delays. According to the 2023 ESC Guidelines, emergency and urgent surgery must be performed within strictly defined timeframes to be effective [12]. In our resource-limited and war-affected setting, patients often arrive from peripheral facilities already hemodynamically unstable, rendering surgery futile by the time of admission. To improve survival, the primary objective must be to reduce the time between surgical indication and intervention through strengthened communication pathways between peripheral hospitals and tertiary centers, facilitating early transfer before the onset of irreversible organ failure.

The in-hospital mortality rate observed in the present study was 28.3%, which exceeds that reported from Saudi Arabia (24.3%), Jordan (13%), and Japan (14.5%) [5, 30, 37]. This highlights the severe challenges in Yemen, where delayed diagnosis, inadequate referral pathways, and limited availability of specialized cardiac surgery centers result in substantially compromised outcomes. Moreover, systemic deficiencies, including a shortage of trained cardiac surgeons, a lack of advanced perioperative care, and the overall fragility of the healthcare system, further diminish the effectiveness of surgical intervention. Addressing these gaps will require urgent investment in infrastructure, as well as the establishment of specialized cardiac centers, the development of targeted training programs for cardiac teams, and the implementation of streamlined referral systems to ensure timely access to life-saving interventions for patients with IE in Yemen.

Our study found an alarmingly high rate of patients complicated by septic shock (17%), which is a sharp increase from the 6% reported previously [6]. While temporal differences in data collection may partially explain this discrepancy, broader contextual factors also appear to have played a major role. The protracted war has significantly constrained the financial capacity of patients to undergo surgical interventions. Given that surgery is central to the management of septic shock, its underutilization, clearly reflected in our findings compared with prior reports, likely contributed to the increased risk of progression to septic shock. These observations underscore how socioeconomic and political determinants of health intersect with clinical outcomes, amplifying the severity of disease in vulnerable populations.

Antimicrobial therapy remains a cornerstone in the management of sepsis and septic shock [39], with early and appropriate administration consistently associated with improved survival rates [40, 41]. In our cohort, septic shock emerged as the strongest independent predictor of in-hospital mortality, consistent with international data [8, 42]. This finding can be attributed to several factors. Mechanistically, septic shock reflects the transition to a systemic inflammatory state characterized by profound circulatory collapse, uncontrolled bacteremia, and multi-organ failure, all of which severely limit survival despite optimal antibiotic therapy. Moreover, patients in septic shock are often poor surgical candidates due to hemodynamic instability and multi-organ dysfunction [42]. These observations are particularly relevant in low-resource settings such as Yemen, where delayed diagnosis, limited access to intensive care, and the restricted availability of timely cardiac surgery exacerbate the lethality of septic shock. The elevated rate of embolic events in the septic shock subgroup (80.0%) compared with the overall rate (38.3%) represents an additional factor compounding the risk of death in critically ill patients. Taken together, our findings emphasize the critical need for early recognition of sepsis, prompt initiation of effective antimicrobial therapy, and timely multidisciplinary intervention to mitigate the devastating impact of septic shock in IE patients.

AKI is a frequent and clinically meaningful complication of IE, largely driven by the profound hemodynamic disturbances that characterize this disease. Such disturbances may arise from the systemic inflammatory response or from cardiogenic complications, most notably congestive HF, which reduces renal blood flow and precipitates prerenal azotemia and continued renal injury [43, 44]. Studies with animal models have demonstrated that AKI can lead to additional structural and functional damage in cardiac tissue [45]. Recent evidence further highlights that baseline renal vulnerability plays a key role, with the baseline glomerular filtration rate (GFR) reported to be the only independent predictor of subsequent AKI development (OR 0.94, p = 0.001) [46]. Beyond its incidence, the clinical impact of AKI is substantial, and patients with IE-associated AKI have markedly higher 90-day mortality [47]. In specialized centers, AKI has been linked to advanced age, elevated baseline creatinine, peripheral embolism, and the development of HF [48]. Moreover, the severity of renal impairment, as reflected by GFR loss and AKI network stage, is strongly associated with in-hospital mortality of IE patients, which itself may reach up to 25% during hospitalization [46]. Large-scale analyses confirm these findings, demonstrating that patients with AKI not only incur significantly greater healthcare utilization and costs [49], but also face increased risks of septic shock (AOR 3.78, 95% CIs: 2.97–4.82, p 0.001) [50]. Long-term outcomes are likewise affected, as early AKI has been associated with higher 1-year mortality (OR 1.65, 95% CIs: 1.03–2.64) and progression to CKD (OR 2.23, 95% CIs: 1.30–3.82) [44]. Collectively, these data demonstrate that AKI is a robust, consistent, and independent predictor of in-hospital mortality in patients with IE. This aligns with our study findings, underscoring the central role of multiorgan dysfunction, particularly renal involvement, in driving early adverse outcomes in this setting.

The present study has several limitations that should be considered when interpreting the findings. First, the investigation was conducted at a single tertiary referral center, which may limit the generalizability of our findings, particularly given the high proportion of critically ill cases managed at this institution. Second, the relatively small sample size (n = 60) and limited number of deaths (n = 17) restricted the statistical power and necessitated the use of penalized logistic regression to avoid overfitting. Although this approach improves model stability, it does not fully eliminate the constraints imposed by low event counts. Third, some clinically relevant variables demonstrated substantial imbalance or near-zero variance, such as vegetation presence (98.3%), heart rhythm, and recommended surgical intervention, thus limiting their ability to meaningfully discriminate outcomes despite their potential prognostic relevance. Fourth, although important echocardiographic features (e.g., vegetation characteristics, LVEF, side of infection) did not show significant associations with mortality in our cohort, this may reflect limited statistical power rather than a true absence of effect. Fifth, while blood culture results were obtained systematically, the high proportion of culture-negative cases inherent to resource-limited settings may have reduced the ability to explore organism-specific risks. Sixth, treatment pathways were influenced by real-world constraints, as only one-third of patients underwent surgery despite almost universal surgical recommendations. This disparity, which reflects challenges in timing, access, and feasibility, may have introduced confounding that could not be fully adjusted for. Finally, as all outcomes were restricted to the in-hospital period, long-term morbidity and mortality were not assessed. Future multicenter studies with larger sample sizes and extended follow-up are needed to validate these findings and refine risk prediction in patients with IE.

In-hospital mortality was alarmingly high in this cohort of IE patients managed at Yemen’s largest tertiary referral center, underscoring the severity of disease presentation in a resource-limited setting. Following rigorous variable selection and bias-reduced modeling, septic shock and AKI emerged as the most robust and independent predictors of in-hospital mortality, highlighting their critical prognostic significance. These findings highlight the central role of early recognition and aggressive management of systemic complications in improving short-term outcomes of IE, particularly in low-resource environments where advanced diagnostic and therapeutic options may be limited. Future multicenter studies with larger cohorts are warranted to validate these predictors and to refine risk stratification strategies that prioritize the prevention and timely management of life-threatening complications.

The data that support the findings of this study are available from the first author and the corresponding author upon reasonable request.

MAG: Conceptualization, Methodology, Formal analysis, Investigation, Data Curation, Writing – Original Draft, Writing – Review & Editing, Visualization, Project administration, Supervision. MA-K: Conceptualization, Methodology, Validation, Investigation, Resources, Writing – Review & Editing, Supervision. TA-M: Methodology, Software, Formal analysis, Data Curation, Writing – Review & Editing, Visualization. AA-H: Conceptualization, Methodology, Formal analysis, Validation, Investigation, Resources, Writing – Review & Editing, Supervision, Project administration, Funding acquisition. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was approved by the Research Ethics Committee (REC) at Al-Razi University (approval number: Ref: RU/17/FMHS/2023, dated: 20 August 2023). The study was conducted in accordance with the 2013 Declaration of Helsinki. Written informed consent was obtained from all participants before enrollment. Patients were informed of their right to withdraw from the study at any time without affecting their medical care. Patient confidentiality was ensured by assigning unique identification numbers and de-identifying all personal and health information.

The authors would like to express their sincere gratitude to the medical and nursing staff of the Cardiology Department at TMGH, Sana’a, for their dedicated patient care and invaluable support during data collection. We also thank the echocardiography unit and the central laboratory team for their assistance with imaging and microbiological investigations. Special appreciation is extended to all patients and their families for their cooperation and trust, which made this study possible.

This research received no external funding.

The authors declare no conflict of interest.