Insight into the epidemiology of infective endocarditis in Portugal: a contemporary nationwide study from 2010 to 2018

Infective endocarditis (IE) is an old and rare disease, with an annual incidence in populational studies of 4 to 10 cases per 100,000 per habitants [1]. Indeed, all IE cases culminate in hospitalization at some point. And despite decades of improvement in the medical and surgical field, a persistent substantial rate of complications and mortality is shown in IE. In fact, worldwide, the intrahospital mortality rate varies among different countries, varying between 8 and 40% [2]. Several factors may contribute to this variation such as the country surveyed, the duration of the research, the analyzed time, variations in the population studied, considered IE case definition and organization of the health systems.

A shift in the epidemiology of endocarditis has been noted in the most recent literature [3‐5], with older and more complex patients, Staphylococcus aureus as an important and emerging agent, a growing susceptible adult population of patients with congenital heart disease or intracardiac prosthesis or devices and chronic renal failure on dialysis. The diagnostic criteria changed in 2000 [6] with the evolution of transesophageal echocardiography and microbiology and in 2015 [7] with the inclusion of new imaging diagnostic techniques such as 18F-FDG PET/CT. Timing of surgery and antibiotic prophylaxis continue to be challenging issues in daily practice.

Little information is known about Portugal’s temporal trends regarding IE incidence and clinical results. The main source of evidence regarding the IE situation in Portugal arises from single-center hospital surveys [8‐12] and conclude that it predominantly occurs in older male patients, with a predominance of Staphylococcus and Streptococcus species and an apparently high rate of intrahospital complications. Nevertheless, several questions remain unanswered regarding epidemiological and outcome results in patients hospitalized with IE in Portugal.

Using populational-based data we aimed to understand the incidence of IE in Portugal, describe its clinical, microbiological, complications and outcome results, and analyze its evolution between 2010 and 2018.

Incidence estimation can only be performed using populational based data. With regards to IE, populational surveys are scarce and with significant variations regarding methodology and results. The reported incidence of IE among different studies is not entirely similar ranging between 3 and 15 cases per 100,000 in population-based studies [15‐27], with considerable differences noted even in similar countries [28]. Still, the findings in Portugal are consistent with the already described values. Additionally, an upper trend in incident IE was noted between 2010 and 2018. The strength of this observation is probably restricted by the fact that we are analyzing a short period. Nevertheless, this has been observed in several developed countries such as Denmark, Italy, England, Spain, Germany, or the Netherlands in the past two decades. This tendency was not noted, however, in other countries such as France, Australia, Scotland or the United States of America (USA) [16, 20]. Reasons to explain this global upper trend in IE incidence in Portugal are various, although some may be speculative as this study does not allow for a cause-effect analysis. Portugal has experienced a gradual increase in life expectancy of the population [29], population aging [30] with a sustained increase in the aging index of the population [31]. This, adding to a growing proportion of patients with comorbidities associated with an increased rate of invasive medical procedures (cardiac and non-cardiac) can partially explain the observed tendency. Of course, the improvement in microbiology, imaging techniques and medical expertise (clinician’s awareness and technical specialization) that are available in the public health system to diagnose IE can also contribute to the observed trend in developed countries.

Regarding microbiology, the data retrieved from discharge notes were scarce (49.5% of the total cohort), probably a result of underreporting—this has been noted in other populational studies such as in Fedeli et al. [18] or Shah et al. [27]. Infectious agents such as Staphylococcus spp. and Streptococcus spp. were the most prevalent in this analysis, with a mild predominance of the former, which is according to other tertiary hospitals series [18, 29, 32]. In fact, in developed countries Staphylococcus has replaced Streptococcus as the most prevalent infectious agent causing IE in the last decades, mainly justified by an increase in invasive medical procedures in the general population as well as a significant population of IV drug use. Our data does not allow for analysis regarding the source of IE (community versus healthcare-associated). On the other hand, the low percentage of patients with opioid consumption or HIV in our cohort is probably related to underreporting or underdiagnosis at the time of hospitalization. Unpredictably, gram-negative bacteria were the third most frequent cause of IE in our study (11.9%), followed by Enterococcus.

The increasing role of cardiac surgery in IE management is well documented in all scientific guidelines [7, 33]. The surgical rate in other populational studies ranged from 15 to nearly 50%; yet, the most recent populational series that included patients hospitalized after 2010 reported heterogeneous surgical rates of 10.6–13.3% (Toyoda et al. [24], USA), 3.8–6.3% (Shah et al. [27], Scotland), 23% (Olmos et al. [26], Spain) and 46.5% (Cresti et al. [25], Italy). Our analysis presented marginally lower values of surgical rate (up to 13.2% at one-year follow-up had had valve surgery), which may be a consequence of an older cohort, with significant comorbidities and a high rate of noncardiac complications as has been described individually in Portuguese single-center surveys [8]. Also, a part of the total cohort may have had surgery after discharge from the incident hospitalization and the IE code may have been underreported in the surgical hospitalization report with loss of that data during this evaluation. An important aspect of our analysis was the demonstration of a clear clinical benefit of surgery which was also noted in the ICE registry [32], in a metanalysis by Head et al. [34] and in other tertiary referral centers surveys [10, 11, 35, 36]. Still, a general described temporal trend is on stability [18, 20, 32, 37], which is consistent with our data, despite more recent series reporting an increasing tendency in Spain [26] and the USA [38].

One-fifth of the cohort died during the index hospitalization. This is in accordance with other already mentioned populational series. Trend analysis revealed an upper tendency consistent with Italian scenario [18, 25] whereas in Denmark [15], Spain [26] and the USA [38] a decrease was registered. Half the cohort presented related complications, being heart failure the most prevalent situation. An increase in the rate of prognostic factors such as older age, comorbidities (cancer or renal chronic disease), infection by Staphylococcus and the presence of IE related in-hospital complications may justify a higher complexity in IE cases that could thus partially explain this higher mortality during the observed period. This once again confirms the malignant nature of this disease—in fact, the multisystemic nature of the presented complications (cardiac, infectious, neurological, renal) is an argument in favor of having a multidisciplinary team of specialists managing this disease in dedicated centers to improve its prognosis at an individual level.

Finally, nearly 10% of the surviving cohort after the first hospitalization with IE were readmitted during the first year. Few studies have analyzed this specific feature. Morita et al. [39] concluded that nearly 25% of their cohort were readmitted during the first 30 days post-discharge. The fact that most of our patients were discharged home or to rehabilitation or palliative care institutions and that the length of hospital stay was considerably higher in our study (median 21 days in our study versus 10 days at Morita et al. study) may have contributed to this disparity.

The general growing incidence of IE in a contemporary cohort in Portugal, the need for prolonged hospitalization, with a significant rate of complications and mortality highlight that IE should be a clinical and national priority.

Between 2010 and 2018 in Portugal, the incidence of infective endocarditis demonstrated a global increase with a deceleration in more recent years, a significant rate of in-hospital complications, a mildly lower than expected stable surgical rate and a still too high and growing mortality rate.

The need to analyze and eventually improve existing advanced clinical protocols, hospital circuits for these patients, and the specialization of local multidisciplinary clinical teams is warranted. Additionally, optimization of national healthcare organization through the definition of specific national referral centers should be sought. Lastly, a better understanding of epidemiology is crucial in justifying and promoting favorable national health policies. This can be achieved through the implementation of a national registry that can prospectively describe IE´s diagnosis and management, the promotion of patients and physicians´ education/awareness programs, and the active intervention on risk factors that are amenable to be altered.