Clinical Research Directory

From Commensalism to Pathogenicity: Exploring the Pathophysiology of Bacteremia to Better Understand Enterococcus Faecalis Infective Endocarditis

Enterococci are pathobionts of the human intestinal microbiota: they colonize the gastrointestinal tract as well as the skin, urine, wounds, bile, the oral cavity and endodontic canal, and medical devices (urinary catheters, venous catheters, etc.). They are responsible for urinary, dental, bloodstream, endocardial, biliary, and gastrointestinal infections. Enterococcus faecalis is the enterococcus most frequently isolated from clinical specimens. It is the third leading cause of infective endocarditis (infection of the cardiac valves) and the leading cause of endocarditis following TAVI (transcatheter aortic valve implantation via the femoral route). E. faecalis infective endocarditis (EFIE) is severe and difficult to treat, with a particularly high relapse rate despite appropriate antibiotic therapy. Cardiac valve contamination is always secondary to E. faecalis bacteremia, particularly in cases of isolated E. faecalis bacteremia (EFIB), defined by the absence of an identifiable portal of entry. Once in the bloodstream, the bacterium adheres to the valvular endothelium (healthy or damaged) through specific virulence factors, including endocarditis- and biofilm-associated pili (ebp), the collagen adhesin Ace, and aggregation substance (Agg). The classical portals of entry for EFIE are infections of the urinary tract and the gastrointestinal tract. However, despite extensive investigations, the source of infection remains unidentified in more than 50% of cases. An imbalance of the intestinal microbiota, leading to overgrowth and subsequent translocation of E. faecalis from the digestive tract into the bloodstream, could explain the absence of an identifiable portal of entry during routine clinical and paraclinical evaluations. This plausible hypothesis remains largely unexplored to date. A better understanding of the underlying pathophysiology-particularly gut dysbiosis and the pathogen's capacity for intestinal translocation-could improve the prevention of EFIE occurrence and relapse.

Long Term Management and Outcomes of Surgical and Non Surgical Infective Endocarditis

Infective endocarditis (IE) is a complex clinical condition in which approximately half of patients require surgical treatment during hospitalization, while the remaining patients are managed medically according to current guideline recommendations. However, limited evidence is available regarding the long-term management and outcomes of patients treated conservatively after completion of antibiotic therapy. The ENDOCARDITIS study is a multicenter, observational study with retrospective and prospective components designed to evaluate long-term outcomes in patients with definite infective endocarditis managed either surgically or with medical therapy alone. Adult patients will be enrolled and followed for up to 24 months. The primary objective is to compare long-term outcomes between surgical and non-surgical patients, while the secondary objective is to define optimal long-term follow-up strategies for patients treated medically.

Anemia Therapy in Patients With Infective Endocarditis

Infective endocarditis (IE) is a bacterial infection of the heart valves, inserted material or surrounding struc-tures and is associated with a high morbidity and mortality. In patients with IE, anemia is considered to result from the underlying infection, prolonged sustained inflammatory response due to the often slow natural course of the disease, and coexisting comorbidities. Previous studies have found that moderate to severe anemia is associated with a markedly higher risk of mortality in the 6-months recovery phase following treatment for IE. In many cardiac patients and patients with chronic inflammation, randomized trials have shown benefit of treatment of anemia with adjunctive therapy i.e., vitamins (vitamin B12/folic acid), intravenous iron, and erythropoiesis stimulating agents in alleviating anemia, without increased risk of infection. Despite these findings, anemia screening and management are not addressed in current endocarditis guidelines. Thus, in patients with IE and anemia, adjunctive treatment of the anemia might be beneficial for recovery and improve outcomes. The aim of POET-IRON is to assess the efficacy of adjunctive anemia treatment in patients with IE, using intravenous iron supplementation, erythropoietin-stimulated erythropoiesis, and dietary optimization including vitamins if necessary, and its effect on hemoglobin levels compared to standard care. The investigators hypothesize that this intervention is safe and will increase hemoglobin concentration, thereby alleviating symptoms of anemia and improving clinical outcomes through enhanced oxygen-carrying capacity, tissue oxygenation, and functional status.

The Study Tests if Preoperative Dental Screening is Superior to no Preoperative Dental Screening in Improving the Outcome of Patients Undergoing Surgical Cardiac Valve Replacement or Transcatheter Cardiac Valve Implantation.

This randomized, multicenter, open-label trial evaluates whether preoperative dental screening improves outcomes in patients undergoing surgical or transcatheter cardiac valve intervention. Participants are randomized 1:1 to preoperative dental screening or no screening. The primary outcome is time to first occurrence of all-cause death, redo-intervention of the index valve, or definite infective endocarditis within 2 years. The study uses registry-based follow-up to ensure complete outcome ascertainment.

Percutaneous AngioVac Vegetation Extraction (PAVE) to Remove Right Heart Vegetations in Patients With Infective Endocarditis

The investigation aims to demonstrate initial safety and efficacy of the AngioVac System for the removal of vegetation in the right heart in patients with infective endocarditis.

Outcomes of Surgical Treatment in Patients With Infective Endocarditis

Infective endocarditis (IE) is a severe disease associated with significant morbidity and mortality despite advances in antimicrobial therapy and cardiac surgery. In complicated cases, surgical intervention is frequently required. This retrospective observational study aims to evaluate outcomes in adult patients undergoing cardiac surgery for infective endocarditis at the Azienda Ospedaliero-Universitaria SS. Antonio e Biagio e Cesare Arrigo of Alessandria. The primary objective is to assess 30-day mortality after surgery and to analyze clinical and surgical factors associated with adverse outcomes. Secondary objectives include the description of epidemiological, clinical, microbiological, and therapeutic characteristics of surgically treated infective endocarditis, the identification of predictors of postoperative complications, and the evaluation of mortality and recurrence of infection at 6 and 12 months after surgery. The study also assesses the consistency between documented surgical indications and the recommendations of the European Society of Cardiology (ESC) guidelines for the management of infective endocarditis.

European Research Group on Outcomes of Surgical Treatment of Infective Endocarditis

The European Research Group on Outcomes of Surgical Treatment of Infective Endocarditis (ERGOSTE) is a nascent large surgical registry that would encompass most relevant aspects of IE in Europe in the contemporary era.

Electronic Archive of Patients With Congenital Heart Disease and Diagnosis of Infective Endocarditis

The objective of the study is to create an electronic archive in which to census all newly diagnosed or already diagnosed cases of infective endocarditis and congenital heart disease after 01 January 2022 at the IRCCS AOU Bologna Pediatric and Developmental Age Cardiology Center so that be able to describe the clinical and echocardiographic features in patients with congenital heart disease and infective endocarditis in this population in order to be able to define new diagnostic/epidemiological hypotheses and the identification of predictive factors of adverse outcome (death, re-intervention, re-hospitalization) in patients with congenital heart disease and EI.