Contemporary management of endocarditis

The diagnosis of infective endocarditis (IE) is often challenging and based on careful integration of clinical, microbiological, and imaging findings. The classical diagnostic scores (e.g. Duke criteria) have drawbacks as they leave clinicians with a considerable number of uncertain cases, in which further management is unclear and important therapeutic actions possibly delayed. Transoesophageal echocardiography is the preferred imaging technique for the diagnosis of IE as it can visualize valvular vegetations and paravalvular complications with high accuracy. However, transoesophageal echocardiography has limitations in the case of device-associated endocarditis (i.e. prosthetic valve (PVE) or cardiovascular implantable electronic device (CIED) infection). Radionuclide imaging techniques using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) or white blood cell single-photon emission computed tomography (WBC SPECT) are accurate techniques to pick-up inflammatory cells. They have shown incremental diagnostic value for detecting PVE and CIED infection. Adding computed tomography angiography allows accurate co-registration of inflammatory signal and anatomical structure, and improves the detection of paravalvular complications such as abscesses or pseudoaneurysms. Current European Society of Cardiology guidelines have recently adopted the use of FDG PET/CT or WBC SPECT/CT in their recommendations for the work-up of suspected or uncertain PVE.

In recent decades, against the background of incidence rate increasing, infectious endocarditis (IE) remains in the category of diseases with a high mortality and a “difficult diagnosis”. According to different studies, 5.2–14.8 % of IE cases were detected only at autopsy or heart surgery, and 27–42.8 % of IE cases with fatal outcome were not diagnosed before death. In 25–66 % patients infectious endocarditis was diagnosed later than 1 month from the onset of symptoms (including later than 3 months in almost a quarter of patients). Late diagnosis, considered as one of the independent risk factors for an unfavorable prognosis of IE (relative risk 2.1), is most frequent with IE in elderly patients. The generally accepted diagnostic criteria of IE, providing a standardized approach to the diagnosis of IE, rely on laboratory and instrumental evidence of bacteremia and visualization of vegetations and signs of valve destruction, as major clinical diagnostic criteria. However, a diagnosis of IE is not suspected at an outpatient stage in 54–79 % of patients, so the necessary transthoracic echocardiographic examination and bacteriological blood tests are not performed. In 84 % cases of right heart valves IE and 27 % of left heart valves IE extracardiac manifestations of the disease due to cardiogenic emboli, immunocomplex mechanisms, or systemic inflammation were initially regarded as an independent disease and patients were hospitalized with incorrect diagnosis. Most often, such masks are associated with involvement of lungs, nervous system, and kidneys, less often rheumatological, vascular, hematological guise and the onset with myocardial infarction or acute abdominal pain are noted. The lecture analyzes the causes of IE diagnosis errors and describes clinical situations that allow suspecting IE, as well as situations in which IE must be considered with a differential diagnosis. Authors emphasize that timely clinical suspicion, with availability of modern effective heart imaging and bacteriological studies remains essential basis for early IE diagnosis.

Infective Endocarditis Involving the Pulmonary Valve

Infective endocarditis (IE) is associated with high mortality and morbidity. Cardiac troponin (Tn) elevation seems to be common in patients with IE and could be associated with a poor prognosis. The aim of this study was to synthesize the prognostic value of Tn in patients with IE. We searched in MEDLINE, EMBASE, and the Cochrane library, including the Cochrane Central Register of Controlled Trials (CENTRAL) until February 2020. Observational studies reporting on the association between Tn and in-hospital and 1-year mortality, and IE complications were considered eligible. As each centre uses different conventional or ultra-sensitive Tn, with different normality threshold, we considered them as normal or elevated according to the criteria specified in each article. Articles were systematically selected, assessed for bias, and, when possible, meta-analysed using a random effect model. After retrieving 542 articles, 18 were included for qualitative synthesis and 9 for quantitative meta-analysis. Compared with patients with normal Tn levels, patients with Tn elevation presented higher in-hospital mortality [odds ratio (OR) 5.96, 95% confidence interval (CI) 3.46-10.26; P < 0.0001], 1-year mortality (OR 2.67, 95% CI 1.42-5.02; P = 0.002), and surgery rates (OR 2.34, 95% CI 1.42-3.85; P = 0.0008). They also suffered more frequent complications: central nervous system events (OR 8.85, 95% CI 3.23-24.26; P < 0.0001) and cardiac abscesses (OR 4.96, 95% CI 1.94-12.70; P = 0.0008). Tn elevation is associated with a poor prognosis in patients with IE. Troponin determination seems to provide additional help in the prognostic assessment of these patients.

BackgroundUnlike enterococcal native and prosthetic valve infective endocarditis (IE), enterococcal CIED infections are not well described.MethodsData from the Multicenter Electrophysiologic Device Infection Collaboration (MEDIC), a prospective, observational, multinational cohort study of CIED infections, were used to provide a descriptive analysis of adult patients with CIED infections due to enterococcal species.ResultsOf 433 patients, 21 (4.8%) were diagnosed with enterococcal CIED infection. Specific data on enterococcal species and antimicrobial susceptibilities were not recorded. The mean age was 70.8 years. No patient had previous CIED infection. Twelve patients (57%) had permanent pacemakers, 5 (24%) had implantable cardioverter defibrillators, and 4 (19%) had biventricular devices. Among the 21 infections, 3 (14%) were categorized as CIED-related bloodstream infections and 18 (86%) as IE; no patient had isolated pocket infection. Of the IE cases, four were valvular IE, eight were lead IE, and six were both. Fourteen cases of IE (78%) were definite by the modified Duke criteria. Median time from last device procedure to infection was 510 days (range 37–2,952 days). The most common presenting symptom was fever (48%); five patients (24%) exhibited local signs of pocket infection. All 21 patients underwent TEE with vegetations demonstrated in 17 (81%). Blood cultures grew enterococci from all patients. The most common antimicrobial regimen was a penicillin plus aminoglycoside (38%); two patients (9.5%) received ampicillin + ceftriaxone. Antibiotics were given for a median of 43 days. Only 14 patients (67%) had complete device removal; the seven patients retaining their device were judged to be at high risk for extraction. There was one death during the index hospital stay with four additional patients dying over the 6 months after therapy (overall mortality 24%); two of the seven patients retaining their CIED died.ConclusionEnterococci caused 4.8% of all CIED infections in our cohort. Most infections appeared to be hematogenous in origin with late onset. IE was the most common infectious syndrome. A penicillin plus aminoglycoside, given for 6 weeks, was the most frequent therapy. Only 67% of patients underwent device removal. At 6 months follow-up, no relapses had occurred but overall mortality was 24%.DisclosuresJ. E. Peacock Jr., Pfizer, Inc.: Shareholder, Owns common stock in Pfizer which was inherited and held in a trust. M. R. Sohail, TyRx Inc.: Investigator, Research support. Medtronic Inc.: Investigator, Research support. Medtronic Inc.: Consultant, Speaker honorarium. Spectranetics: Consultant, Speaker honorarium. Boston Scientific Corp: Consultant, Speaker honorarium. L. M. Baddour, UpToDate: Collaborator, Royalty payment. J. M. Miro, Abbvie: Consultant and Grant Investigator, Consulting honoraria and Research grant. Bristol-Myers Squibb: Consultant and Grant Investigator, Consulting honoraria and Research grant. Genentech: Consultant and Grant Investigator, Consulting honoraria and Research grant. Medtronic: Consultant and Grant Investigator, Consulting honoraria and Research grant. Novartis: Consultant and Grant Investigator, Consulting honoraria and Research grant. Gilead Sciences: Consultant and Grant Investigator, Consulting honoraria and Research grant. Pfizer: Consultant and Grant Investigator, Consulting honoraria and Research grant. ViiV Healthcare: Consultant and Grant Investigator, Consulting honoraria and Research grant. A. J. Greenspon, Medtronic: Consultant, Speaker honorarium. Boston Scientific: Consultant, Speaker honorarium. St. Jude: Consultant, Speaker honorarium. R. G. Carrillo, St. Jude Medical Group: Speaker’s Bureau, Research support. Spectranetics: Consultant, Speaker honorarium. Sorin Group: Speaker’s Bureau, None. Boston Scientific Corp: Speaker’s Bureau, None. D. Z. Uslan, Medtronic: Investigator, Research support. Boston Scientific: Consultant, Speaker honorarium.

HRS Expert Consensus Statement on remote interrogation and monitoring for cardiovascular implantable electronic devices.

Background: Due to a high frequency of concomitant cardiac disease, many patients with end-stage renal disease on hemodialysis (HD) have indications for cardiac implantable electronic devices (CIED). Patients on HD have increased morbidity and mortality compared to the general population. Additionally, there is increased risk for infection. Limited outcomes data exist for HD patients undergoing transvenous lead extraction (TLE). We sought to compare the mortality rates following TLE in HD patients vs. patients not on HD undergoing TLE. We also compared the mortality rates between these two groups when the indication for extraction was infection (pocket infection or endocarditis). Methods: We conducted a retrospective cohort study including patients on HD who underwent TLE between August 1996 and December 2009. Mortality rates were obtained using the Social Security Death Index and were compared to mortality rates of patients not on HD undergoing TLE during this same time period. Results: The study population included 63 patients (median age 70.0, IQR 18.3) on HD at the time of TLE. The control population included 2557 patients (median age 67,2, IQR 20.0 ) that underwent TLE during the same time period. Procedural mortality rate was 0.002% in the control group and 0% in the HD group. Mortality at 30 days, 1 year, and 3 years was significantly higher in HD patients (23.8%, 54.0% and 92.1%) compared to non HD patients (1.91%, 10.24%, and 20.41%). In the HD group, patients with pocket infection or infective endocarditis had higher mortality rates at 30 days, 1 year, and 3 years (27.45%, 60.78%, and 92.15%) than patients undergoing TLE due to infection but not on hemodialysis (2.9%, 13.28% and 25.55%). (Table 1) Conclusions: Despite equivalent and very low procedural mortality rates in patient on HD compared to control, subsequent mortality rates in patients on HD at the time of TLE far exceeds the mortality rate after TLE in patients not on HD. Mortality rates are elevated even further in patients on HD that undergo TLE for infection.

BackgroundComplete removal of cardiac implantable electronic devices (CIEDs) is recommended in patients with CIED infections, including both systemic and localized pocket infection. The aim of the study was to provide an up-to-date and comprehensive assessment of evidence relating to the effect of complete CIED extraction in patients with a CIED infection. MethodsWe performed a systematic review and meta-analysis of studies reporting short- and mid-term outcomes in patients who had a device infection or infective endocarditis (IE) and underwent complete removal of the cardiac device (generator and leads) compared to those who received conservative therapy (no removal, partial removal, local antibiotic infiltration or isolated antibiotic therapy). The primary outcome was reinfection/relapse. Secondary outcomes were short-term (30-day/in-hospital) and mid-term (mean follow-up: 43.0 months) mortality. Random effects model was performed. ResultsThirty-two studies met the criteria for inclusion in the final analysis. Patients with complete CIED extraction (n = 905) exhibited a lower rate of relapse/re-infection compared to patients (n = 195) with a conservative treatment approach (n = 195, OR 0.02, 95%CI 0.01–0.06, p < 0.0001, mean-follow-up: 16.1 months). Additionally, these patients displayed a lower short- (OR 0.40, 95%CI 0.23–0.69, p = 0.01) and mid-term (OR 0.52, 95%CI 0.34–0.78, p = 0.002) mortality. ConclusionsThe analysis indicates that patients with a CIED infection who undergo complete CIED extraction exhibit a lower rate of relapse/re-infection. Additionally, a lower short- and mid-term mortality is observed, although it is acknowledged that this outcome may be influenced by treatment allocation bias.

Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is associated with high mortality and surgery is rarely performed. Thus, to inform on preventive measures and treatment strategies, we investigated patient characteristics and microbiology of IE after TAVI. Using Danish nationwide registries, we identified patients with IE after TAVI, IE after non-TAVI prosthetic valve (nTPV), and native valve IE. Patient characteristics; overall, early (≤12 m), and late IE (>12 m) microbiology; and unadjusted and adjusted mortality were compared. We identified 273, 1022, and 5376 cases of IE after TAVI, IE after nTPV, and native valve IE. Age and frailty were highest among TAVI IE (4.8%; median age: 82 y; 61.9% frail). Enterococcus spp. were common for IE after TAVI (27.1%) and IE after nTPV (21.2%) compared with native valve IE (11.4%). Blood culture-negative IE was rare in IE after TAVI (5.5%) compared with IE after nTPV (15.2%) and native valve IE (13.5%). The unadjusted 90-day mortality was comparable, but the 5-year mortality was highest for IE after TAVI (75.2% vs 57.2% vs 53.6%). In Cox models adjusted for patient characteristics and bacterial etiology for 1-90 days and 91-365 days, there was no significant difference in mortality rates. Patients with IE after TAVI are older and frailer, enterococci and streptococci are often the etiologic agents, and are rarely blood culture negative compared with other IE patients. Future studies regarding antibiotic prophylaxis strategies covering enterococci should be considered in this setting.

Radionuclide Imaging of Infective Endocarditis.

Background Left-sided infectious endocarditis (IE) has a high 1-year mortality. Anemia is a common finding in patients with IE, yet little is known about frequency, severity, and associated outcomes in this setting. Purpose To examine the relationship between Hemoglobin (Hgb) level measured at IE stabilization (time of randomization) in the Partial Oral versus intravenous Antibiotic Treatment of Endocarditis (POET) trial - and long-term all-cause mortality. Methods In the POET trial, 400 patients with left-sided IE were randomized, after medical and/or surgical stabilization, to conventional antibiotic treatment or partial oral treatment. Only non-surgically treated patients were considered in this study. Patients were divided by quartiles into four groups based on Hgb level at randomization. Results We examined 248 patients with non-surgically treated IE. Median time from diagnosis of IE to randomization was 14 days (IQ 12–19). At long-term follow-up (median 3.2 years, IQ 2.18–4.60), 71 patients had died (28.6%). Patients in the lowest quantile (Hgb ≤6.0 mmol) had a HR of 4.17 (95% CI 1.81–9.61, p&amp;lt;0.001) for death compared to patients in the highest quantile (Hgb &amp;gt;7.5 mmol/L). This association remained significant after multivariable adjustment for age, sex, renal disease, C-Reactive Protein, and Prosthetic heart valve (HR 2.69, 95% CI 1.11–6.50); p=0.028). Conclusion Low Hemoglobin level at stabilization in patients with IE was associated with an increased risk of long-term mortality. Whether intensified treatment of anemia in patients with IE could improve long-term outcome requires investigation. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Danish Heart Foundation, The Capital Regions Research Council

Infective endocarditis is one of the most serious complications of structural heart disease. It occurs primarily in children and adolescents with preexisting anatomic abnormalities of the heart, with an incidence that varies with the specific cardiac lesion. An identifiable potential source of bacteremia precedes infective endocarditis in approximately one fifth of cases in children. The high mortality (19% to 25%), morbidity, and prolonged treatment course of infective endocarditis make its diagnosis, management, and prevention a matter of great importance to pediatricians. PREDISPOSING FACTORS Structural Heart Disease Cardiac malformations are the major predisposing factor to infective endocarditis. Although rheumatic heart disease has gradually declined as a substrate for endocarditis, the increased survival of children with congenital heart disease in the past two decades has increased the number and age of children susceptible to infective endocarditis. In general, lesions leading to a high velocity of blood flow through a heart valve, septal defect, or blood vessel are associated with increased susceptibility to endocarditis (Table 1). Children at highest risk are those with cyanotic congenital heart disease (eg, tetralogy of Fallot), ventricular septal defect with aortic regurgitation, left-sided valvar regurgitation or obstruction, prosthetic valves, and recent cardiac surgery. Endocarditis is exceedingly uncommon in individuals with isolated atrial septal defect secundum and with mild pulmonic valve stenosis.

Background Infective endocarditis (IE) is a life-threatening condition with high in-hospital mortality rates. In recent decades, the implementation of endocarditis teams has been proposed as a multidisciplinary approach to improve patient outcomes. Our aim was to evaluate prognosis over a fifteen-year period in a national cohort. Methods Our data come from the Spanish endocarditis registry. We included 6525 patients diagnosed with IE between 2008 and 2022. Clinical characteristics, complications, and mortality rates were compared in four periods (2008-2011, 2009-2014, 2015-2017, 2018-2022). Results We found a worsening of the clinical profile during the four periods, with an increase of median age (68-69-69-70 years, p=0.007), age-adjusted Charlson comorbidity index (4-5-5-5, p &amp;lt;0.001), prosthetic valve IE rate (29-31-32-33%, P=0.029) and intracardiac complications rate (27-30-37-38%, p&amp;lt;0.001), and a decrease in the rate of cardiac implantable electronic devices infections (11-11-9-8%, p=0.012). However, the rate of surgical interventions increased (45-45-49-51%, p&amp;lt;0.001) and the median number of days from diagnosis to surgery decreased (12-10-9-9. P=0.001). Inhospital death decreased in the overall population (27-25-25-23%, p=0.037) and in high risk patients as those aged 70-77 years (31-32-28-23, p=0.04), ≥78 years (36-33-34-30, p=0.07), Charlson index ≥7 (38-39-38-31, p=0.02), treated with surgery (22-21-18-18, p=0.02), and prosthetic valve IE (32-27-30-25, p=0.001). One-year mortality also decreased (36-35-33-28%, p=0.008). Year period was an independent risk factor for inhospital mortality (odds ratio 0.97, 95% confidence interval 0.95-0.98, p &amp;lt;0.001) and one-year mortality (hazard ratio 0.93, 95% confidence interval 0.88-0.99, p=0.016) Conclusions Despite a worsening clinical profile, IE inhospital and one-year mortality seem to be decreasing. The introduction of endocarditis teams and an increase in surgical interventions might contribute to this better prognosis. Our findings suggest that adopting a multidisciplinary team approach could be a critical strategy in improving outcomes for patients with IE.

As in many other infectious diseases 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) positron emission tomography (PET) combined with computed tomography (CT) (18F-FDG-PET/CT) has shown obvious potential in cardiovascular infections, although several issues remain unclarified with regard to acquisition and patient preparation protocols. Overall, 18F-FDG-PET/CT should be considered an important complementary diagnostic technique in infectious endocarditis, and cardiac device related infections, especially for extracardiac disease state. Also, monitoring of the metabolic response to antibiotics should be considered a promising indication, and the high negative predictive value of 18F-FDG-PET/CT is also of great clinical relevance. The purpose of this work was to present the current evidence regarding the role of 18F-FDGPET/ CT in infectious endocarditis, extracardiac complications, and cardiac implantable electronic devices. Keywords: 18F-FDG-PET/CT, infectious endocarditis, cardiac implantable electronic device infection, left ventricular assist devices.

Infective endocarditis is a serious disease that is often diagnosed with a considerable delay in clinical practice and therefore has a high mortality rate; therefore, early diagnosis and antibiotic treatment are extremely important. Epidemiological shifts in the age profile, new risk factors and the increasing use of intravascular prosthetic materials have led to changes in the microbial spectrum and clinical symptoms, which must be taken into account in the diagnostic efforts and therapy. Nonspecific symptoms and the increase in nosocomial endocarditis, especially in critically ill and immunocompromised patients require a high level of diagnostic expertise. With diagnostic algorithms based on guideline recommendations antibiotic treatment has to be initiated as early as possible. For patients with severe infective endocarditis a cardiac surgeon has to be involved from an early stage of the disease as in about 50 % of cases conservative antibiotic therapy alone does not alleviate the infection. Also early surgical treatment should be sought with the onset of complications. After effective treatment and patient survival there will always be an increased risk of suffering from renewed endocarditis. This is taken into account in the new recommendations of the European Society of Cardiology for the prevention of infective endocarditis.