Infective Endocarditis Research Articles

Preliminary results from the Polish Infective Endocarditis Registry (POL-ENDO): time to change clinical approach?

Abstract Background/Aims: Infective endocarditis (IE) is a severe valve disease associated with high morbidity and mortality. The aim of this preliminary study was to evaluate the profile and treatment outcomes of IE in Poland based on the POL-ENDO registry. Methods A prospective cohort, multicenter, observational study - the POL ENDO registry - of IE patients from 134 hospitals in Poland recruited between August 2022 and August 2023 was performed. We evaluated demographic, clinical, imaging, and treatment outcome data. A comparison of the Polish patients with those assessed in the ESC-EORP EURO-ENDO registry was performed. Results Among a total of 880 IE patients, 622 were male (70.7%). The POL-ENDO participants were older (61.4±16.7 years vs. 59.25±18.03 years, p=0.001). Native valve IE (NVIE) occurred more often in Poland (82.3% vs. 56.6%, p <0.001). Transthoracic echocardiography (TTE) was performed more frequently in Poland (93.6% vs. 89.8% p<0.001). New imaging techniques (CT/MRI/PET/SPECT) were less frequently used in Poland (CT: 53.2% vs. 41.3%, p<0.001; MRI: 18.7% vs. 6.4%, p<0.001). Heart failure (HF) occurred more often in Poland as inhospital complication (31.4% vs. 14%, p<0.001). Surgical treatment was less performed in Poland (51.2% vs. 36.9%, p<0.001). Inhospital mortality was higher in Poland (21% vs. 17%, p=0.008). Conclusion Polish patients with IE were significantly older and more comorbid. New imaging techniques are less frequently used in Poland. Echocardiography was performed more frequently in Poland as the diagnostic mainstay. Surgical treatment was significantly less frequent in Poland. Inhospital mortality in Poland is greater. The change of clinical practice in Poland should be considered.

18F-FDG PET/CT in the diagnosis of infective endocarditis

Abstract Background Increased uptake of 18F-fluorodeoxyglucose (FDG) by positron-emission tomography/computed tomography (PET/CT) is one of the diagnostic criteria for prosthetic valve endocarditis (PVE). However, there is limited data on the diagnostic value of FDG PET/CT in diagnosing native valve endocarditis (NVE) and semi-quantitative parameters of FDG uptake. Purpose The objective of this retrospective study was to evaluate the accuracy of FDG PET/CT and additional value of semi-quantitative measures of FDG uptake in the detection of NVE and PVE. Methods All patients who had undergone FDG PET/CT due to suspected infective endocarditis (IE) at a single tertiary referral center between 2010 and 2020 were identified. Additional patients who underwent FDG PET/CT for detecting an infection focus were included as controls. Clinical reports were evaluated and images were analyzed for maximal standardized uptake value (SUVmax) and target to background ratio (TBR = SUVmax normalized to mean blood pool SUV) around valves. The scan was defined positive based on either clinical reading or previously proposed cut-off values for SUVmax and TBR (>4.2 and >2.1, respectively). The final diagnosis of IE was defined based on all available information in electronic medical records. Results The study cohort included 16 patients with suspected NVE (median age 58 years, 88% male), 24 patients with suspected PVE (median age 72 years, 92% male) and 37 patients who underwent FDG PET/CT for detecting an infectious focus (8 with a prosthetic valve). The final diagnosis was definite IE in 25 (14 PVE), possible IE in 7 (6 PVE), and no IE in 45 (12 with a prosthetic valve). Overall, clinical reading of FDG PET/CT identified 17 (sensitivity 68%) of definite IE with a specificity of 91% and accuracy of 83%. Compared with NVE, the sensitivity of FDG PET/CT was higher in the detection of PVE (46% vs. 86%) whereas specificity was lower (97% vs. 75%) resulting in small difference in accuracy (84% vs. 81%). In PVE, SUVmax had higher sensitivity (93%) than clinical reading, resulting in the same accuracy (81%) despite lower specificity (67%). A combination of either positive clinical reading or positive SUVmax identified all patients with PVE (sensitivity 100%). In NVE, TBR had higher sensitivity (64%) than clinical reading, but accuracy (66%) and specificity (67%) were significantly lower. Conclusions FDG PET/CT shows high sensitivity in the detection of PVE and high specificity in the detection of NVE in a real-world clinical cohort. Semi-quantitative parameters of FDG uptake can improve sensitivity of detecting PVE maintaining diagnostic accuracy. However, in NVE semi-quantitative parameters were associated with a prominent reduction in specificity.

The 5-Item Modified Frailty Index (mFI-5) for risk stratification of patients with infective endocarditis undergoing cardiac surgery

Abstract Background population aging has led to an increased burden of frailty as an emerging global health issue, and variables for its quantification in patients with infective endocarditis (IE) are lacking in current surgical risks scores. The 5-item modified frailty index (mFI-5) score has shown to be effective in the prediction of surgical outcomes in other medical scenarios. Purpose this study aimed to assess the role of the mFI-5 in the prediction of surgical outcomes in patients with left-sided IE undergoing cardiac surgery. Methods a total of 112 cases of confirmed left-sided IE undergoing surgery, were consecutively collected and followed during one year after diagnosis in two tertiary hospitals between 2016 and 2021. The mFI-5 score included 5 baseline patient-specific comorbidities: diabetes, congestive heart failure, non-independent functional status (Barthel index <80), hypertension and chronic obstructive pulmonary disease (range 0-5), and patients were categorised as mFI-low (<2, n=65), and mFI-high (>=2, n=47). Results mean age was 66 [SD 15] years, 67% were men and community-acquired infections were 75%. As shown in Table 1, mFI-high patients were older and, aside from the specific comorbidities included in the score, with more chronic kidney disease. The most isolated pathogen was S. viridans (n=32), predominantly in mFI-low, in contrast to enterococcal and polymicrobial IEs, which were more frequent in mFI-high. Larger vegetations were reported in mFI-high [16 (10) vs 13 (9) mm, p 0.03], with no differences regarding infection site or periannular complications. Acute kidney injury, decompensated heart failure and higher natriuretic peptides were more common in mFI-high. Regarding mortality, in-hospital deaths were more frequent in mFI-high group. When analyzing mFI-score as a discrete variable, in-hospital mortality was associated with higher median scores values [2 (2) vs 1(1) points, p 0.02], being 2 points the optimal cutoff point for prediction [AUC 0.64 (95% CI 0.54-0.73), Fig.1A]. Among survivors who completed follow-up (n=82), rehospitalization and all-cause mortality rates in mFI-high exceeded those from mFI-low. Predictors of in-hospital and 1-year mortality were assessed by logistic regression (Fig. 1B), confirming the independent prognostic association of mFI-5-score in patients with IE undergoing surgery. Conclusions patients with IE undergoing cardiac surgery with higher mFI-5 scores were older, more predisposed to enterococcal and polymicrobial infections, and had a greater comorbidity burden with a more complicated clinical course. The mFI-score was independently associated with in-hospital mortality as well as rehospitalizations and 1-year mortality, positioning itself as an additional tool for risk stratification in this cluster of patients.Table 1Figure 1

Clinical management and outcomes of patients with infective endocarditis according to frailty status

Abstract Background infective endocarditis (IE) remains a severe condition associated with a remarkably high mortality in certain groups of patients Purpose the aim of this study was to compare both the clinical management and short and mid-term prognosis of patients with IE according to their frailty status. Methods: a total of 200 cases of confirmed IE were consecutively collected in two tertiary hospitals between September 2016 and February 2021, and prospectively followed during one year after diagnosis. Patients were categorised according to the 5-item FRAIL scale as: Group A (n=48), for scores >2, and Group B (n=152), for scores <=2. Results mean age was 70 [SD 15] years, 64% were men and community-acquired infections were 69%. Baseline and clinical data are shown in Table 1. Enterococci were more frequent in Group A, but no significant differences were found regarding infection site, presence of vegetations or periannular complications, time to diagnosis or length of stay. During hospitalization, acute heart failure, delirium and bronchoaspiration were more common among frail patients. Unlike 18F-FDG PET/CT, which was more frequently done in Group B (34 vs 17%, p 0.03), transesophageal echocardiography was similarly performed between groups (92 vs 97%, p 0.08). Less frail patients underwent cardiac surgery (42 vs 68%, p 0.001), with a larger proportion of inoperable patients despite meeting surgical criteria (29 vs 12%, p 0.002). In-hospital mortality was higher in Group A, both overall and by therapeutic strategies, except in those inoperable patients with surgical indication but treated conservatively, where mortality did not differ between groups. Among survivors who completed follow-up (n=144), although recurrence rates were similar, readmission (75 vs 35%, p <0.001) and all-cause mortality rates (36 vs 5%, p <0.001) in Group A exceeded those from Group B. Predictors of in-hospital and 1-year mortality were assessed by logistic regression (Fig. 1), confirming the independent prognostic role of baseline FRAIL score in patients with IE [OR 1.5 (1.2-2.3) and 2.0 (1.5-2.6), respectively, for every additional scale point]. Conclusions frail patients with IE were older, more prone to enterococcal infections and in-hospital complications and had greater comorbidity burden. Both PET/CT and cardiac surgery were less performed in this group, which was characterized by a higher predicted surgical risk, as well as a worse short and mid-term prognosis.

Mechanical thrombectomy is associated with worse outcomes in infective endocarditis: a retrospective cohort study

Abstract Background Acute Ischaemic stroke (AIS) is a common complication in infective endocarditis (IE) and associated is with high mortality. There is a paucity of data evaluating mechanical thrombectomy (MT) in patients with AIS secondary to IE. Our retrospective cohort study aimed to quantify the efficacy and safety of MT in this patient population. Methods The National Inpatient Sample (NIS) was utilised. We obtained data from 2004 – 2019. We included all patients who had AIS and IE. We excluded patients who received thrombolysis. Those who received mechanical thrombectomy were compared to those who did not. Odds ratios were calculated using logistic regressions. We adjusted for multiple confounders. Outcomes included inpatient mortality, long length of stay (> 4 days), discharge status (normal vs ‘other’) and intracranial haemorrhage. Results The sample population consisted of 22,6390 patients (mean age 69, 52.3% female). ME was performed on 496 (2.2%). Patients with IE who received MT had a greater odds of death compared to those who did not (OR 1.91 95% CI 1.00 – 3.67). In addition, they had a greater odds of intracranial bleeding (OR 4.47 95% CI 2.78 – 7.20). Length of stay and neurological outcome did the significantly differ. We performed a sub-analysis, which included patients who had received thrombolysis in addition to MT. This did not modify the results for mortality and intracranial bleeding outcomes. Conclusion Mechanical thrombectomy was associated with increased mortality and intracranial bleeding in patients who have AIS associated with IE. While acknowledging the limitations of observational data, we therefore advise caution when considering mechanical thrombectomy in this patient population.

First in-human study of 64Cu-DOTATATE positron emission tomography/computed tomography(PET/CT) in infective endocarditis: a prospective head-to-head comparison with 18-FDG PET/CT

Abstract Background Infective endocarditis (IE) is a severe and potentially fatal condition, which can be challenging to diagnose. Positron emission tomography/computed tomography (PET/CT) with [18F]fluorodeoxyglucose ([18F]FDG) is proposed as a diagnostic tool in the ESC endocarditis guidelines, but holds limitations. Purpose To compare the tracer uptake between [64Cu]Cu-DOTATATE and [18F]FDG in patients with IE, and to examine sensitivity and specificity in patients with prosthetic valve endocarditis (PVE) or native valve endocarditis (NVE). Methods The CuDOS-study was a prospective study including 20 cases with IE (10 with PVE and 10 with NVE) and 20 controls. [64Cu]Cu-DOTATATE and [18F]FDG PET/CT were performed in all participants. Scans were read blinded to clinical data. Tracer uptakes were measured as maximum standardized uptake values (SUVmax) in each heart valve. A visual interpretation of the presence or absence of IE was recorded for [64Cu]Cu-DOTATATE and [18F]FDG, respectively. Results The median age of the cases and controls was 68 years [IQR 53-71] and 61 years [IQR 56-67], respectively. In cases and controls, 85% and 70% were men, respectively. [64Cu]Cu-DOTATATE uptake (median SUVmax [IQR]) in patients with IE was higher than in controls (2.38 [1.87-2.90] vs. 1.43 [1.30-1.56], p<0.001), although this difference was mainly driven by PVE-cases (2.99 [2.22-3.75] vs. 1.43 [1.30-1.56 (controls), p<0.001) and to a lesser extent the NVE-cases (1.78 [1.22-2.33] vs. 1.43 [1.30-1.56 (controls), p=0.079), Figure 1. The sensitivity of [64Cu]Cu-DOTATATE and [18F]FDG PET/CT in 20 cases and the 20 controls were comparable, and the specificity was 90% and 75%, respectively. The analysis of PVE versus the 20 controls showed equal sensitivity (80%) for [64Cu]Cu-DOTATATE and [18F]FDG PET/CT and a specificity of 90% and 75%, respectively. The difference in the specificity between [64Cu]Cu-DOTATATE and [18F]FDG was 15% [IQR -5.9-36%], p=0.38. Conclusion [64Cu]Cu-DOTATATE PET/CT showed relevant uptake in the infected valve in patients with infective endocarditis. [64Cu]Cu-DOTATATE had a numerically higher specificity than [18F]FDG in prosthetic valve endocarditis, although the difference was not statistically significant. Both tracers were limited in the detection of native valve endocarditis.Figure 1 [64Cu]Cu-DOTATATE and [18F]FDG

Controlling Nutritional Status (CONUT) Score: a new tool for characterization and prognosis of patients with infective endocarditis

Abstract Background malnutrition is a marker of unfavorable prognosis in different medical conditions, however, the association between new objective immunonutritional indexes and outcomes for patients with infective endocarditis (IE) is not fully studied. Purpose the aim of this study was to assess the role of the Controlling Nutritional Status (CONUT) Score in the characterization of patients with IE and its association with prognostic outcomes. Methods a total of 184 cases of confirmed IE were consecutively collected and followed during one year after diagnosis in two tertiary hospitals. CONUT score was calculated using serum albumin, total cholesterol and lymphocyte count [(range 0-12), the higher, the worse] at diagnosis, and patients were categorised as CONUT-high (>=6, n=98), and CONUT-low (<6, n=86) based on the sample median value. Results mean age was 70 [SD 15] years, 64% were men and community-acquired infections were 69%. Median score value was 6 (4). As shown in Table 1 and 2, diabetes and frailty were more prevalent in CONUT-high group, who showed a worse profile of nutritional biomarkers. Overall, the most frequent pathogen was S. viridans (n=43). By groups, S. aureus was predominantly isolated in CONUT-high (20 vs 8%; p 0.02), and non-viridans streptococci in CONUT-low (9 vs 2%, p 0.03). Regarding infection site, IE of aortic bioprostheses was more common in CONUT-high, whereas mechanical aortic valves and mitral bioprostheses were more frequently involved in CONUT-low. Larger vegetations [14 (11) vs 11 (7) mm, p 0.02], and more periannular abscesses (25 vs 13%, p 0.04) were detected in CONUT-high, who presented more acute kidney injury and septic shock during hospitalization. Despite higher predicted surgical risk in CONUT-high, neither the proportion of patients who underwent surgery nor in-hospital mortality, differed between groups. When analyzing according to the therapeutic approach, only among those medically managed patients without surgical indication, in-hospital mortality was higher in CONUT-high. At 1-year follow-up, rehospitalization rate tended to be lower in those with a better nutritional status (35% vs 51%, p 0.07). Conclusions in patients with IE and a high CONUT score, diabetes and frailty were more prevalent. In addition, virulent pathogens, larger vegetations and periannular complications were more frequently reported. Although surgery performance and in-hospital mortality did not differ between groups, a worse nutritional status was associated with a higher rate of clinical complications and higher mortality among patients with conservative management who did not meet surgical criteria.

Acute renal failure in patients with infective endocarditis

Abstract Background/Introduction Acute kidney failure (AKF) appears in a high percentage of patients with infective endocarditis (IE), becoming a complication related to the mortality of the disease and delayed recovery of patients. Purpose To investigate the factors that are related to the development of AKF in patients with IE. Methods Study of all cases of IE consecutively diagnosed in an university hospital between 2005 and 2021. A disease extension protocol was carried out using imaging tests and the levels of potentially nephrotoxic antibiotics were monitored. Furthermore, starting in 2010, a multidisciplinary committee (MC) was created to follow patients with EI. Factors potentially related to the development of AKF during hospital admission according to RIFLE criteria were analyzed using a binary logistic regression analysis. Results 305 cases were included, 96.7% of them meeting definitive IE criteria. The median age was 66 (54-74.5) years, 75.4% male. The most frequent microorganism was S. aureus (66; 21.6%), 172 (56.4%) underwent surgery and 107 patients (35.1%) died. 149 cases (45.3%) developed AKF, with no differences before (45.3%) and after the creation of the CM. The variables related in the multivariate analysis to the appearance of AKF were age (OR 1.01; 95% CI: 1.01-1.05; p= 0.006), baseline creatinine (OR= 1.53; 95% CI = 1.22-1.68; p<0.001). ), peripheral embolism (OR=1.86; 95% CI = 1.07-3.22; p= 0.027), the development of heart failure (OR=1.98; 95% CI = 1.12-3.22; p= 0.017) and left ventricular systolic dysfunction (OR= 4.02; 95% CI = 1.09-14.85; p= 0.037). None of the other variables analyzed, including the type of microorganism and the use of nephrotoxic antibiotics, were related to the development of AKF. Conclusions In a hospital center with a protocol for the study and treatment of infective endocarditis, the development of AKF is related to age, baseline creatinine, peripheral embolism, and the development of heart failure.

Bacteremia after transcatheter aortic valve implantation: a nationwide cohort study

Abstract Background Bacteremia and infective endocarditis (IE) are rare but severe complications to transcatheter aortic valve implantation (TAVI). However, data on early bacteremia and microbiological etiological profile are scarce. Purpose The study aimed to investigate the incidence of bacteremia and IE within six months after TAVI. Methods Using Danish nationwide registries, we identified all patients who underwent TAVI from 2012 to 2021. These patients were matched 1:1 by age, sex, and index-year with individuals who underwent elective coronary angiography (CAG). The primary outcomes were bacteremia and IE within six months. Outcomes were compared with cumulative incidence functions and adjusted hazard ratios (HR). All patients were followed six months from the index date until the outcome of interest, death, emigration, or end of study (December 31st, 2021), whichever came first. Results We identified 5,990 patients undergoing first-time TAVI, of whom 56 % were men, and the median age was 81 years [IQR 77–85]. All patients were matched with controls undergoing CAG (56% men, median age 81 [IQR 77-85]). Patients undergoing TAVI had more comorbidities than controls. The six-month cumulative incidence of bacteremia was 4.2% [95% CI 3.7-4.7] and 2.6% [95% CI 2.2-3.0] after TAVI and CAG, respectively, corresponding to an adjusted HR of 1.57 (95% CI 1.27-1.96) (Figure 1). The common bacterial etiologies for bacteremia after TAVI were Streptococci (20%), Coagulase-negative staphylococci (CoNS) (19%), and Enterococci (18%). After CAG, CoNS (22%) and Staphylococcus aureus (16%) were the most frequent. By six months, 1.1% [95% CI 0.9-1.4] and 0.2% [95% CI 0.1-0.3] developed IE after TAVI and CAG, respectively, with an adjusted HR of 20.01 (95% CI 5.97-67.48). Conclusion In this nationwide cohort study, the risks of bacteremia and infective endocarditis within six months post-TAVI were significantly higher than in the matched coronary angiography population. Bacteremia post-TAVI was characterized by significantly more Enterococci spp. These results could have implications in the selection of peri-procedural antibiotics, as commonly used antibiotic regimens do not cover Enterococci spp.Cumulative incidence of bacteremia

Postoperative heart valve infection, when and which bacteria: a nationwide cohort study

Abstract Background In patients undergoing heart valve surgery, subsequent bacteremia and infective endocarditis are feared events due to the associated high mortality. Knowledge on the incidence and specification of bacteremia following left-sided valve surgery are sparse and may have implications for prophylactic strategies and follow-up. Purpose To examine the six months incidence of bacteremia and infective endocarditis following left-sided heart valve surgery. Methods In the period from January 2010 to December 2021 all patients undergoing left-sided valve surgery were identified using Danish nationwide registries. Patients were followed until a maximum of six months, end of study, emigration, death, or outcome of interest (i.e., bacteremia or infective endocarditis). Cumulative incidence curves were computed with death as a competing risk stratified on bacterial species and for subgroups of interest: type of valve surgery, age, and sex. Results A total of 14,305 patients were included in the study. The majority of the study population were male (68.6%), and the median age was 70.2 years (25th-75th percentile 62.0-76.0 years). In total, 10,469 (73.2%) of the study population underwent aortic valve surgery, 3,497 (24.5%) underwent mitral valve surgery, while 339 (2.4%) underwent surgery on both valves. The cumulative incidence of bacteremia at six months of follow-up was 2.4% (95% CI 2.2-2.7%), Figure 1. For the overall study population, the most frequently occurring bacteremia was with Coagulase-negative Staphylococci (28%) and Staphylococcus aureus (14%). Within 30 days 0.35% of the patients had bacteremia with coagulase-negative staphylococci while this was 0.68% at six months of follow-up. For Staphylococcus aureus this was 0.19% and 0.34%, respectively. The cumulative incidence of infective endocarditis at six months of follow up was 1.0% (95% CI 0.8-1.2%). The majority of the infective endocarditis incidents were blood culture negative (27%) or caused by Enterococci (19%), Streptococci (17%) or Coagulase-negative Staphylococci (17%) while Staphylococcus aureus accounted for 14%. In crude analysis, simultaneous surgery on the mitral and aortic valve was associated with a statistically significant higher rate of bacteremia (P=0.004). Similarly, higher age was associated with a statistically significant higher rate of bacteremia (P<0.001). On the contrary, in crude analysis, no difference in the risk of bacteremia was found between sexes (P=0.9). Conclusions Bacteremia following left-sided heart valve surgery occurred in little over 2%. The majority was with Staphylococci, and half of these occurred within 30 days of the surgery. There is a continued need to optimize prophylactic strategies.

Increased risk of infective endocarditis following transurethral resection of the prostate (TUR-P)

Abstract Background Transient bacteremia is a well-known complication of transurethral resection of the prostate (TUR-P). Still, the associated risk of bacteremia and subsequent infective endocarditis (endocarditis) after TUR-P has been sparsely examined. Purpose To examine the risk of bacteremia and infective endocarditis following TUR-P. Methods We identified all patients who underwent TUR-P between 2010-2020 with ICD-10 codes from Danish nationwide registries. Patients were compared to an age-matched cohort of males from the general population (1:1 match-ratio). We defined a 6-month exposure window following TUR-P and examined the risk of bacteremia and endocarditis within the first 6 months and compared with the following 6-12 months after TUR-P. Microbiology findings were based on complete data on blood culture results. Incidences of bacteremia and endocarditis were calculated, and groups were compared with cumulative incidences. To account for predisposing endocarditis risk factors, multivariable time-dependent Cox regression analyses were performed on the associated risk of bacteremia and endocarditis. Results In total, 25.781 patients underwent TUR-P. Median age was 70.7 years (IQR: 64.9-76.3). Incidence of bacteremia was higher in the TUR-P group than the control group (727.47 [681.49-776.56] per 10,000 person years vs 84.75 [95% CI: 70.19-102.35)] per 10,000 person years). Incidence of endocarditis was also higher in the TUR-P group than the control group (34.64 [95% CI: 25.78-46.55] per 10,000 person years vs 3.14 [95% CI: 1.18-8.35] per 10,000 person years). In 72.7% of endocarditis-cases, Enterococcus Faecalis was the disease-causing pathogen in the TUR-P group. As compared with an age-matched control group, we found an increased associated risk of bacteremia in patients undergoing TUR-P within the first 6 months from the procedure (adj. HR: 7.72 [95% CI: 6.25-9.53]) and the increased risk persisted within the following 6-12 months (adj. HR 2.31 [95% CI: 1.83-2.91]). TUR-P was also associated with endocarditis within 6 months from the procedure (8.16 [95% CI 3.06-21.79]), but not significantly the following 6-12 months after (2.15 [95% CI: 0.91-5.07]) as compared with the age-matched control group. Conclusion Transurethral resection of the prostate (TUR-P) is associated with an almost 8 times increased risk of bacteremia and an 8 times increased risk of infective endocarditis. Our findings emphasize the necessity for development of better preventive strategies against infective endocarditis after TUR-P.Risk of endocarditis post-TUR-P

Changes in length of hospital stay for infective endocarditis - data from before and after the POET trial

Abstract Background The results from the Partial Oral Treatment of left-sided Endocarditis (POET) trial was published in August 2018 and established non-inferiority of a switch to oral step-down antibiotic treatment in stabilized patients with infective endocarditis (IE). However, data on length of hospital stay and safety following the POET trial are warranted. Purpose To examine the changes in length of hospital stay before and after POET publication. Further, to assess safety (relapse of bacteremia and 180 days of mortality) before and after POET publication. Methods By cross-linkage of Danish nationwide registries, patients with first-time IE caused by Streptococcus spp., Enterococcus faecalis, Staphylococcus aureus, or coagulase negative staphylococci from 2012-2021 were identified. Immediately following the publication of the POET trial, the POET criteria was implemented and used in Denmark. The study period was categorized according to publication date (before and after September 2018). Median length of hospital stay was examined according to calendar period. Mortality (from admission date) and relapse of bacteremia (after discharge) at 180 days of follow-up were examined with the Kaplan-Meier estimator and the Cumulative Incidence Function, respectively. Results We identified 3,008 patients before publication of the POET trial (median age 72.8 years) and 1,740 after the publication (median age 75.2 years) (p<0.0001). The burden of comorbidities was comparable between groups. The median length of hospital stay decreased by 8 days: 41 days (IQR: 29-49) before POET publication and 33 days (IQR: 21-44) after POET publication (p<0.0001 for difference), Figure 1. Similar reductions in length of hospital stay were seen across different microbiological etiologies and age groups. The reduction in length of hospital stay was most pronounced in non-surgically treated patients. The mortality from IE admission with a maximum of 180 days follow-up was 27.5% before POET publication and 28.3% after POET publication (p-value=0.41 for difference). The bacteremia relapse rate within 180 days was 3.5% before POET publication and 1.6% after POET publication (p-value=0.0002 for difference), Figure 2. Conclusion Following the POET trial, we found an 8 days reduction in median length of hospital stay with no change in mortality and an associated lower rate of relapse of bacteremia.

Gender disparities and infective endocarditis burden in the United States and European Union: a comparative analysis

Abstract Background Despite improvement in diagnostics and treatment options, infective endocarditis (IE) remains a significant burden for healthcare systems. While high-income countries have improved diagnosis of IE, the progress in interventional cardiology with a rise in cardiac devices associated infections, and people migrations offset some of these gains. Purpose To the best of our knowledge, there is a lack of comparative data between high-income countries, including the United States (US) and European Union (EU). Methods We collected the age-standardized rates of incidence (ASIR), deaths (ASDR), and disability-adjusted life years (ASDALYs) in the US and EU from 1993 to 2019 with the Global Health Data Exchange query tool. The Bayesian geospatial regression analysis and estimated annual percentage change (EAPC) to quantify the trends in age-standardized rates (ASR) were used. The data were stratified based on the gender, year, and location. Results Males in the US had an overall ASIR of 17.2/100k with an increasing trend between 1993 and 2019, and an annual average rate of change of 0.8 % (EAPC of 0.8%). A similar trend and higher rates were noted in males in the EU, with ASIR of 20.9/100k and EAPC of 2.0%. For the same period, females in the US had lower ASIR than females in the EU (11.9/100k vs. 13.6/100k) , and lower annual percent change (1% vs. 1.3%). In the US, ASDR was higher in males than females (1.6/100k vs. 1.28/100k), but females had higher annual percentage change (EAPC of 2.7% in males and 3.3% in females). Compared to US, males and females in the EU had lower ASDR in 2019 (1.2/100k in males, and 1.0/100k in females) with lower annual percentage changes of 2.5% and 1.7%, respectively. The ASDALY was significantly higher in the US, for both males (34.6/100k) and females (25.5/100k), with a greater increase in an annual average rate of change of 2.7% in females than in males (2.2%). EU males had ASDALY of 24.9/100k with an EAPC of 1.8%, while females had 16.7/100K with an annual average increase of 1.2%. Figure 1, Table 1 Conclusion ASIR of IE appears to be higher in the EU for both males and females. Conversely, ASDR and ASDALY manifest higher rates in the US across both genders, with females notably demonstrating a higher annual percentage increase for these metrics. Further studies are needed to assess the nature of these differences and to inform health policies.The age-standardized rates in US and EUThe differences in the EAPC

Mitral valve reoperation versus first-time surgery for mitral regurgitation: comparison of patient characteristics, type of surgery and mortality in a nationwide cohort

Abstract Background Mitral valve reoperation has been estimated to carry higher surgical risk than first-time mitral surgery. Contemporary data on this area is needed as these associations may lead to under-treatment of recurrent mitral valve disease requiring intervention. Purpose To compare patient characteristics, type of surgery, and early mortality related to mitral valve reoperation versus first-time surgery for mitral regurgitation in a nationwide setting. Methods We identified patients ≥18 years undergoing first-time surgery for mitral regurgitation 1996-2021 using Danish nationwide registries. Patients undergoing first-time surgery due to endocarditis were excluded. The study population was categorized into 1) patients who underwent first-time surgery only; 2) patients who underwent mitral reoperation. The first group was followed from date of first-time surgery, while second group was followed from date of reoperation, and baseline characteristics were defined according to their respective index dates. Mortality was examined during 180-day follow-up using the reverse Kaplan-Meier estimator and multivariate Cox analysis was used to compare mortality rates within 30 days and 180 days of follow-up. Subgroup analysis was conducted after excluding patients undergoing reoperation for infectious endocarditis (IE). Results We identified 7,470 patients; 7,058 (94.5%) underwent first-time surgery only and 412 (5.5%) underwent mitral reoperation. Compared to patients who only underwent first-time surgery, reoperated patients were younger (median age 60 vs. 67) and had fewer comorbidities at time of reoperation, Table 1. Prosthetic replacement was performed in 35.6% of first-time surgeries and 77.2% of reoperations. Mortality after 30 days was 5.2% after first-time surgery and 3.2% after reoperation, while 180-day mortality were 7.8% and 10.6%, respectively, Figure 1. Compared to first-time surgery, reoperation was associated with no significant difference in 30-day mortality (HR=0.68, 95%CI 0.39-1.19), but an increased rate of 180-day mortality (HR=1.60, 95%CI 1.17-2.19, p=0.003). After excluding patients with IE in the reoperation group (n=57), mortality was 2.8% and 8.8% after 30 and 180 days, respectively. In this subgroup, compared to first-time surgery, the 30-day rate of mortality was HR=0.61 (95%CI 0.32-1.14) and after 180 days HR=1.34 (95%CI 0.93-1.93, p=0.11). Conclusion Compared to patients who only underwent first-time mitral surgery, patients undergoing mitral reoperation were younger and had fewer comorbidities at time of reoperation. Repair was favoured for first-time surgery, while prosthetic replacement was favoured for reoperations. Compared to first-time surgery, reoperation was associated with an increased risk of 180-day mortality. Though patients undergoing reoperation for mitral valve disease are carefully selected, our findings suggest that this procedure should still be considered at high risk of an adverse outcome.Table 1Figure 1

Risk assessment using DEVI and CARPREG -1 score to predict maternal adverse cardiac cvents in pregnancies with valvular heart disease: external validation study from MPAC registry

Abstract Background Even though many risk assessment tools in pregnant women with valvular heart disease (VHD) are available, validation studies are few that assess their performance in diverse settings, which is needed prior to the application of routine clinical practice. Objectives To validate and establish the clinical utility of two risk stratification tools – DEVI (VHD-specific tool) and CARPREG-I in predicting adverse cardiac events in pregnant patients with VHD. Methods This cohort study involved consecutive pregnancies complicated with VHD enrolled in the prospective MPAC registry from July 2016 to December 2019(1). The ability to discriminate those with and without adverse cardiac outcomes was assessed using the area under the curve for both the DEVI and CARPREG-1 scores. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis. Results Among 1029 pregnancies complicated with heart disease in the MPAC registry cohort, 604(52.3%) with valvular heart disease were included in this analysis. One or more composite adverse cardiac events occurred in 70 (11.6%) pregnancies during antenatal or the early postpartum period. Mitral regurgitation was the most common lesion (67.7%). In assessing the pregnancy outcomes, those who continued past 20 weeks were included, with the majority (92.0%) delivered at term, and the cesarean rates were 33.6% (n=203). The most common adverse event was heart failure (n=32, 5.3%), most of which (68.6%) occurred in the postnatal period. There were 11 maternal deaths (1.8%) during the study period, six among those with mechanical heart valves (four prosthetic valve thrombosis), two among those with severe mitral stenosis and pulmonary hypertension and two with severe mitral regurgitation and infective endocarditis. The area under the receiver operating characteristic curve (AUC) was 0.766, with 95% confidence intervals (CI) 0.703- 0.828 for DEVI and 0.703 (95%CI 0.644- 0.763) for CARPREG-I models. Calibration plots suggested that the DEVI score overestimates risk at higher probabilities, whereas the CARPREG-I score underestimates the risk at most probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 60%. Conclusion In this external validation study in pregnant women with primary rheumatic VHD, DEVI and CARPREG-I scores showed good discrimination ability and clinical utility across various probabilities. Both can be used to classify those who develop adverse cardiac outcomes during pregnancy and childbirth. However, both models need recalibration to improve the agreement between the predicted and observed events prior to routine application in diverse clinical settings.Figure 1.a and b ROC and Decision Curves

Clinical features of infective endocarditis affecting cardiac implantable electronic devices

Abstract Introduction Infective endocarditis (IE) is a serious condition with high rates of serious complications and mortality. Furthermore, implantation of cardiac electronic devices (peacemakers, ICD, CRT) has been increasing in recent years, with technique-associated infections being one of the main adverse events. Our goal was to analise clinical features of IE as associated with cardiac implantable electronic devices (IE-CIED) and its prognostic impact. Methods Prospective study of a cohort of patients diagnosed with IE in our centre from 1987 to 2022. A comparative analysis was performed between patients with IE not associated with cardiac implantable electronic devices (group 1) and those who did (group 2). Clinical, microbiological, echocardiographic and therapeutic variables were analysed and the prognostic impact was evaluated in terms of mortality. Results 569 patients were analysed, of which 540 (94,9%) belonged to group 1, while 29 (5,1%) belonged to group 2. The mean age was higher in group 2 (65,1 years ±12,9 vs 55,7 years ± 18,7; p=0,011) with male predominance in both populations (67.5% overall). Patients with IE-CIED had a higher proportion of staphylococcus aureus (48.3% vs 19.7%; p<0.001) and staphylococcus epidermidis (34.5% vs 15.6%; p<0.001) infections; nosohusial endocarditis (56.5% vs 20.9%; p<0.001); and underlying heart disease (89.7% vs 67.3%; p=0.012). Furthermore, these patients had a higher proportion of tricuspid valve involvement (18.2% vs 81.8%; p<0.001). Regarding the approach, a higher percentage of surgery was performed in patients with IE-CIED (75.9% vs52.7%; p=0.015). On the other hand, patients with IE not associated to cardiac implantable electronic devices had a higher prevalence of cardiac complications (51.5%vs25.7%;p=0.003), defined as valvular rupture or perforation, pseudoaneurysm, abscess or intracardiac fistula; and central nervous system complications (17.2%vs2.9%;p=0.29). No significative differences were found in terms of echocardiographic findings compatibles with IE, nor were there any differences in severe complications or early, late or total mort ality. Conclusions Infective endocarditis affecting cardiac implantable electronic devices is associated to higher prevalence of staphylococci, underlying heart disease and less involvement of the left heart chambers. Surgery was used to a greater extent in this patients. This entity does not imply a worse prognosis in terms of severe complications or mortality.Table 1.Proportion of IE-CIEDTable 2.Microbiology, mortality

Incidental non-infectious masses on cardiac implantable electronic device leads

Abstract Introduction Incidentally detected masses on the leads of cardiac implantable electronic devices (CIED) present a clinical challenge, raising suspicion of infective device endocarditis. Data on the prevalence of such findings are scarce and outdated. Purpose Our aim was to determine the prevalence and evaluate predisposing clinical factors of incidental non-infectious CIED lead masses during transoesophageal echocardiography (TOE). Methods In this retrospective single-centre study, we analysed all TOE examinations performed in patients with CIED leads between January 2010 and November 2023. Patients with suspected or confirmed infectious endocarditis were excluded from this study. Patients with and without incidental non-infectious lead masses were compared regarding clinical characteristics, anticoagulation, type of CIED, and indication for TOE. Results In total, 120 patients with CIED were included. Twenty-five patients (20,8%) presented with non-infectious CIED lead masses. Laboratory findings and cardiovascular risk factors, such as arterial hypertension, dyslipidaemia, diabetes mellitus or chronic kidney disease did not differ significantly between both groups. Moreover, no association was observed between the incidence of CIED lead masses and the type of CIED implanted. Of notice, patients without therapeutic anticoagulation had significantly higher prevalence of CIED lead masses (OR 2.59, 95% CI: 1.04-6.46.; p=0.02), whereas the distribution of CHA2DS2-VASc scores did not differ significantly between both groups. Conclusion Non-infectious CIED lead masses in TOE is a frequent incidental finding. The absence of the oral anticoagulation seems to be the only clinical risk factor for such finding in our study, suggesting possible thrombogenic etiology. The high prevalence of incidental non-infectious lead masses should be kept in mind in order to avoid overdiagnosis of CIED infection and unnecessary lead extraction.

Drug-use-associated infective endocarditis in Denmark

Abstract Introduction Infective endocarditis (IE) has high mortality and the incidence is rising. Intravenous drug use is a risk factor for IE and poses challenges in clinical care. Amid the opioid crisis in many countries, rates of drug-use-associated IE (DU-IE) are increasing. While drug use in Denmark has remained stable the last decade, little is understood about the features and prognostic impact of DU-IE in developed nations not facing a current opioid crisis. Further, with multiple preventive measures deployed in local Danish regions, data on the evolution of DU-IE are warranted. Purpose To examine the temporal evolution, baseline characteristics, and long-term rates of all-cause mortality and IE recurrence in patients with DU-IE compared with patients with non-DU-IE. Methods This nationwide cohort study identified all first-time IE-patients (1999-2018) and categorized them in 1) patients with DU-IE, and 2) patients with non-DU-IE. Drug use was defined using ICD-8/10 codes or treatment for opioid use disorder. Patients were followed from the date of discharge, and absolute one-year rates of mortality and IE recurrence were examined with Kaplan-Meier estimates and the cumulative incidence function, respectively. Outcomes were compared with a multivariable adjusted Cox model. Results We identified 8,843 patients with IE: 407 (4.6%) with DU-IE (61% male, median age 44 years) and 8,436 (95.4%) with non-DU-IE (66% male, median age 72 years). While the absolute number of DU-IE increased, the proportion of DU-IE decreased from 5.9% in 1999-2003 (n=87) to 3.8% in 2014-2018 (n=114). Patients with DU-IE had a higher proportion of bloodstream infection with Staphylococcus aureus (49.4% vs 26.7%, p<0.001); conversely, they had a lower proportion of bloodstream infections with Streptococcusspecies (14.4% vs. 26.2%, p<0.011). Patient with DU-IE had lower in-hospital mortality compared with non-DU-IE (15.5% vs. 20.9%, p<0.001). Among those surviving admission, the one-year cumulative incidence of all-cause mortality was 16.9% in DU-IE and 17.3% in non-DU-IE (p=0.82), yet in adjusted analysis, DU-IE was associated with a higher one-year mortality rate (HR 1.64 [95% CI:1.23-2.21]) (Figure). The one-year cumulative incidence of IE recurrence was 12.8% in DU-IE and 4.3% in non-DU-IE, which corresponded to an adjusted HR of 3.39 (95% CI:2.35-4.88) in DU-IE. Conclusion While an increase in the absolute number of patients with DU-IE was observed, the proportion among all IE-patients was on the decline in Denmark until 2018—which contrasts with other countries where physicians currently battle collateral damage of the opioid crisis. Although drug use was associated with lower in-hospital mortality, it was striking that even though patient with DU-IE was almost 30 years younger, they still had higher rates of all-cause mortality and a more than three-fold increase in IE recurrence one year following discharge.

Clinical, echocardiographic, and pathologic characteristics of patients with pathology-proven nonbacterial thrombotic endocarditis

Abstract Background Non-bacterial thrombotic endocarditis (NBTE) is a non-infectious condition characterized by thrombotic and/or inflammatory depositions involving the cardiac valves. It is a challenging diagnosis of exclusion. Purpose This study aimed to better characterize patients with pathologically proven NBTE and assess its clinical, echocardiographic characteristics and prognostic implications. Methods We retrospectively identified patients with pathology-proven NBTE at a single center. Patients with positive preoperative blood cultures, a history of active or treated infective endocarditis, or identification of valvular organisms by special stains were excluded from the study. Patients with pathology reports of valve perforation or chordal rupture were also excluded because of the high likelihood of an infectious etiology for these lesions. Results A total of 53 patients with NBTE (median age 57 years; 61% females) were identified. In this cohort, 22% had a history of malignancy, 30% had connective tissue disease, 32% had coronary artery disease, and 11% prior history of NBTE. Neurological events accounted for 18 (34%) of the presenting symptoms (TIA n=17, CVA n=9), while new valvular dysfunction in 7 (13%) and fever in 8 (15%) of patients. Five patients (9%) had NBTE involving more than one valve. NBTE involved the mitral valve in 64%, aortic valve in 38% prosthetic/mechanical valve in 11%, and tricuspid valve in 5%. NBTE was identified at the time of autopsy in 34% of patients. NBTE recurred in 3 patients during follow-up. Excluding patients diagnosed at the time of autopsy, 9% of patients died within 1 year of NBTE diagnosis. Conclusion NBTE was diagnosed pathologically in the presence of hyper-inflammatory states due to critical illness or immunological diseases. It was predominantly on the left side of the heart and was associated with embolic phenomena, either clinically or on imaging. Patients diagnosed with antemortem with NBTE have a high mortality in the first year (9%).

Effectiveness of contemporary risk stratification in patients with hypertrophic cardiomyopathy: a pilot study

Abstract Introduction Risk stratification and primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is a challenging discipline. When using current stratification systems, there is always a compromise between sensitivity and specificity. Objective In our pilot study, we sought to determine the incidence of SCD and the effectiveness of stratification systems, i.e., the ESC HCM Risk-SCD score and the system of individual major risk factors (RF) according to ACC/AHA in patients followed in an expert center. Methods Patients with HCM were risk-stratified and followed for 10 ± 8 years at the referral HCM center. Results Five hundred and five patients were stratified, and 71 (14%) were implanted with a cardioverter-defibrillator (ICD) based on risk stratification. ICD patients were stratified at age 39 ± 17 years, of which 26 (35%) were women, maximal left ventricular wall thickness (MLWT) was 23 ± 7 mm, and left atrial dimension (LA) 46 ± 7 mm. During follow-up, 12 (17%) patients had ≥ 1 appropriate ICD therapy at age 46 ± 19 years. Patients with ≥ 1 appropriate ICD therapy had an average 5-year ESC score of 1.8 ± 0.4% and an average ACC/AHA major RF of 1.4 ± 0.8, MLWT 25 ± 6 mm, LA 47 ± 7 mm. None of the ICD patients died of SCD. Five (7%) patients suffered from ICD complications, including 4 (6%) inappropriate shock, and one patient experienced infective endocarditis requiring system extraction. During follow-up, 118 (23%) patients died, of which 28 (6%) from HCM-related causes, 12 (2%) from stroke, 11 (2%) from advanced heart failure, one perioperatively (myectomy) and 4 (1%) patients died suddenly (SCD). The mean age of SCD patients at the time of stratification was 59 ± 14 years; all were male, MLWT 18 ± 5 mm, LA 49 ± 2 mm, mean ESC score 2.0 ± 0.9%, and three (75%) had no RF present according to ACC/AHA. The ESC HCM Risk-SCD score was markedly less sensitive (sensitivity 56%; 95% CI 21-86) but more specific (specificity 98%; 95% CI 96-99) than the ACC/AHA approach (sensitivity 77%; 95% CI 46-95; and specificity 71%; 95% CI 67-75) (Figure). Conclusion With current risk stratification, albeit imperfect, SCD is rare in HCM patients managed at an expert center.