Streptococcal infective endocarditis: clinical features and outcomes according to species.

PURPOSE: Infective endocarditis (IE) is frequently caused by streptococcal species, yet clinical features and mortality are poorly investigated. Our aim was to examine patients with streptococcal IE to describe clinical features and outcomes according to streptococcal species. METHODS: From 2002 to 2012, we investigated patients with IE admitted to two tertiary Danish heart centres. Adult patients with left-sided streptococcal IE were included. Adjusted multivariable logistic regression analyses were performed, to assess the association between streptococcal species and heart valve surgery or 1-year mortality. RESULTS: Among 915 patients with IE, 284 (31%) patients with streptococcal IE were included [mean age 63.5 years (SD 14.1), 69% men]. The most frequent species were S. mitis/oralis (21%) and S. gallolyticus (17%). Fever (86%) and heart murmur (81%) were common symptoms, while dyspnoea was observed in 46%. Further, 18% of all cases were complicated by a cardiac abscess/pseudoaneurysm and 25% by an embolic event. Heart valve surgery during admission was performed in 55% of all patients, and S. gallolyticus (OR 0.28 [95% CI 0.11-0.69]) was associated with less surgery compared with S. mitis/oralis. In-hospital mortality was 7% and 1-year mortality 15%, without any difference between species. CONCLUSION: S. mitis/oralis and S. gallolyticus were the most frequent streptococcal species causing IE. Further, S. gallolyticus IE was associated with less heart valve surgery during admission compared with S. mitis/oralis IE. Being aware of specific symptoms, clinical findings, and complications related to different streptococcal species, may help the clinicians in expecting different outcomes.

Streptococcal species as a prognostic factor for mortality in patients with streptococcal bloodstream infections.

PURPOSE: Streptococcal bloodstream infections (BSIs) are common, yet prognostic factors are poorly investigated. We aimed to investigate the mortality according to streptococcal species and seasonal variation. METHODS: Patients with streptococcal BSIs from 2008 to 2017 in the Capital Region of Denmark were investigated, and data were crosslinked with nationwide registers for the identification of comorbidities. A multivariable logistic regression analysis was performed to assess mortality according to streptococcal species and season of infection. RESULTS: Among 6095 patients with a streptococcal BSI (mean age 68.1 years), the 30-day mortality was 16.1% and the one-year mortality was 31.5%. With S. pneumoniae as a reference, S. vestibularis was associated with a higher adjusted mortality both within 30 days (odds ratio (OR) 2.89 [95% confidence interval (CI) 1.20-6.95]) and one year (OR 4.09 [95% CI 1.70-9.48]). One-year mortality was also higher in S. thermophilus, S. constellatus, S. parasanguinis, S. salivarius, S. anginosus, and S. mitis/oralis. However, S. mutans was associated with a lower one-year mortality OR 0.44 [95% CI 0.20-0.97], while S. gallolyticus was associated with both a lower 30-day (OR 0.42 [95% CI 0.26-0.67]) and one-year mortality (OR 0.66 [95% CI 0.48-0.93]). Furthermore, with infection in the summer as a reference, patients infected in the winter and autumn had a higher association with 30-day mortality. CONCLUSIONS: The mortality in patients with streptococcal BSI was associated with streptococcal species. Further, patients with streptococcal BSIs infected in the autumn and winter had a higher risk of death within 30 days, compared with patients infected in the summer.

Prevalence of Infective Endocarditis in Streptococcal Bloodstream Infections Is Dependent on Streptococcal Species.

BACKGROUND: Streptococci frequently cause infective endocarditis (IE), yet the prevalence of IE in patients with bloodstream infections (BSIs) caused by different streptococcal species is unknown. We aimed to investigate the prevalence of IE at species level in patients with streptococcal BSIs. METHODS: We investigated all patients with streptococcal BSIs, from 2008 to 2017, in the Capital Region of Denmark. Data were crosslinked with Danish nationwide registries for identification of concomitant hospitalization with IE. In a multivariable logistic regression analysis, we investigated the risk of IE according to streptococcal species adjusted for age, sex, ≥3 positive blood culture bottles, native valve disease, prosthetic valve, previous IE, and cardiac device. RESULTS: Among 6506 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men) the IE prevalence was 7.1% (95% CI, 6.5-7.8). The lowest IE prevalence was found with Streptococcus pneumoniae (S pneumoniae) 1.2% (0.8-1.6) and Spyogenes 1.9% (0.9-3.3). An intermediary IE prevalence was found with Sanginosus 4.8% (3.0-7.3), Ssalivarius 5.8% (2.9-10.1), and Sagalactiae 9.1% (6.6-12.1). The highest IE prevalence was found with Smitis/oralis 19.4% (15.6-23.5), Sgallolyticus (formerly Sbovis) 30.2% (24.3-36.7), Ssanguinis 34.6% (26.6-43.3), Sgordonii 44.2% (34.0-54.8), and Smutans 47.9% (33.3-62.8). In multivariable analysis using S pneumoniae as reference, all species except S pyogenes were associated with significantly higher IE risk, with the highest risk found with S gallolyticus odds ratio (OR) 31.0 (18.8-51.1), S mitis/oralis OR 31.6 (19.8-50.5), S sanguinis OR 59.1 (32.6-107), S gordonii OR 80.8 (43.9-149), and S mutans OR 81.3 (37.6-176). CONCLUSIONS: The prevalence of IE in streptococcal BSIs is species dependent with S mutans, S gordonii, S sanguinis, S gallolyticus, and S mitis/oralis having the highest IE prevalence and the highest associated IE risk after adjusting for IE risk factors.

Proposal for the use of echocardiography in bloodstream infections due to different streptococcal species.

BACKGROUND: Infective endocarditis (IE) is diagnosed in 7-8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs. METHODS: In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk < 3%, moderate-risk 3-10%, high-risk 10-30% and very high-risk > 30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3-10%), or "wait & see" (IE < 3%). RESULTS: We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to "wait & see" strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence. CONCLUSION: In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography.

Prevalence of infective endocarditis in patients with positive blood cultures: a Danish nationwide study.

AIMS: Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSIs). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE. METHODS AND RESULTS: By crosslinking nationwide registries from 2010 to 2017, we identified patients with BSIs typically associated with IE: Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), Streptococcus spp., and coagulase negative staphylococci (CoNS) and examined the concurrent IE prevalence. A trend test was used to examine temporal changes in the prevalence of IE. In total 69 021, distributed with 15 350, 16 726, 19 251, and 17 694 BSIs were identified in the periods of 2010-2011, 2012-2013, 2014-2015, and 2016-2017, respectively. Patients with E. faecalis had the highest prevalence of IE (16.7%) followed by S. aureus (10.1%), Streptococcus spp. (7.3%), and CoNS (1.6%). Throughout the study period, the prevalence of IE among patients with E. faecalis and Streptococcus spp. increased significantly (P = 0.0005 and P = 0.03, respectively). Male patients had a higher prevalence of IE for E. faecalis, Streptococcus spp., and CoNS compared with females. A significant increase in the prevalence of IE was seen for E. faecalis, Streptococcus spp., and CoNS with increasing age. CONCLUSION: For E. faecalis BSI, 1 in 6 had IE, for S. aureus BSI 1 in 10 had IE, and for Streptococcus spp. 1 in 14 had IE. Our results suggest that screening for IE seems reasonable in patients with E. faecalis BSI, S. aureus BSI, or Streptococcus spp. BSI.

Staphylococcus aureus Bacteremia in Children Aged 5-18 Years-Risk Factors in the New Millennium.

OBJECTIVES: To assess the association between comorbidities and Staphylococcus aureus bacteremia in children aged 5-18 years, thus, in children with a matured immune system. Further, we aimed to identify presumably healthy children acquiring bacteremia. STUDY DESIGN: By cross-linking nationwide registries, we consecutively included all children born from 1995 onward at their 5-year birthday or date of immigration during 2000-2015. We examined incidence rate ratios (IRR) between preselected exposures and microbiologically verified S aureus bacteremia (reference = children without exposure) using Poisson regression models. RESULTS: We followed 1 109 169 children in 2000-2015 during which 307 children (incidence rate: 3.7 per 100 000 person-years) acquired S aureus bacteremia (methicillin-resistant S aureus = 8; 2.6%). Children without known comorbidities or recent contact with the healthcare system comprised 37.1% of infected children. The highest IRRs were observed in children undergoing dialysis or plasmapheresis (IRR = 367.2 [95% CI) = 188.5-715.3]), children with organ transplantation (IRR = 149.5 [95% CI = 73.9-302.2]), and children with cancer (IRR = 102.9 [95% CI = 74.4-142.2]). Positive associations also were observed in children with chromosomal anomalies (IRR = 7.16 [95% CI = 2.96-17.34]), atopic dermatitis (IRR = 4.89 [95% CI = 3.11-7.69]), congenital heart disease (IRR = 3.14 [95% CI = 1.92-5.11]), and in children undergoing surgery (IRR = 3.34 [95% CI = 2.59-4.28]). Neither premature birth nor parental socioeconomic status was associated with increased disease rates. CONCLUSIONS: S aureus bacteremia is uncommon in children between 5 and 18 years of age. Risk factors known from the adult population, such as dialysis, plasmapheresis, organ transplantation, and cancer, were associated with the highest relative rates. However, prematurity and parental socioeconomic status were not associated with increased rates. Approximately one-third of infected children were presumably healthy.

The associations between socioeconomic status and risk of Staphylococcus aureus bacteremia and subsequent endocarditis - a Danish nationwide cohort study.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is the leading cause of infective endocarditis in several countries. Since socioeconomic status (SES) is known to influence the risk of infectious diseases in general, we aimed to investigate the association between SES and SAB, and risk of subsequent endocarditis in a nationwide adult population. METHODS: All Danish residents were consecutively included at age ≥ 30 years during 1996-2010. We obtained information on SES (highest attained educational level), comorbidities, and microbiologically verified SAB by cross-linking nationwide registries. The incidence rate ratios (IRRs) of SAB and later endocarditis were investigated using Poisson regression models adjusted for sex, age and year (reference = highest SES). RESULTS: Our study population comprised 3,394,936 individuals (median age = 43.2 years). Over a median follow-up of 15.9 years, 13,181 individuals acquired SAB. SES was inversely associated with SAB acquisition, which declined with increasing age, e.g. in individuals with lowest SES, IRRs were 3.78 (95% confidence interval [CI] = 2.89-4.95) in age 30-50 years, 1.87 (CI = 1.60-2.18) in age > 50-70 years and 1.31 (CI = 1.11-1.54) in age > 70 years (interaction-p < 0.0001). Adjustment for comorbidities attenuated the IRRs, but the pattern persisted. No association between SES and endocarditis risk among patients with SAB was observed. CONCLUSIONS: Decreasing SES was associated with an increased risk of SAB, particularly in younger adults. SES was not associated with risk of subsequent endocarditis.

Familial clustering of unexplained heart failure - A Danish nationwide cohort study.

AIMS: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. METHODS AND RESULTS: Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29-2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69-9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40-9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75-10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90-19.49]. CONCLUSION: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated.

Risk of Sudden Infant Death Syndrome Among Siblings of Children Who Died of Sudden Infant Death Syndrome in Denmark.

Importance: Sudden infant death syndrome (SIDS) remains a leading cause of death during the first year of life. The etiology of SIDS is complex and remains largely unknown. Objective: To evaluate whether siblings of children who died of SIDS have a higher risk of SIDS compared with the general pediatric population. Design, Setting, and Participants: This register-based cohort study used Danish nationwide registers. Participants were all infants (<1 year) in Denmark between January 1, 1978, and December 31, 2016, including siblings of children who died of SIDS. Siblings were followed up from the index cases' date of SIDS, date of birth, or immigration, whichever came first, and until age 1 year, emigration, developing SIDS, death, or study end. The median (IQR) follow-up was 1 (1-1) year. Data analysis was conducted from January 2017 to October 2022. Main Outcomes and Measures: Standardized incidence ratios (SIRs) of SIDS were calculated with Poisson regression models relative to the general population. Results: In a population of 2 666 834 consecutive births (1 395 199 [52%] male), 1540 infants died of SIDS (median [IQR] age at SIDS, 3 [2-4] months) during a 39-year study period. A total of 2384 younger siblings (cases) to index cases (first sibling with SIDS) were identified. A higher rate of SIDS was observed among siblings compared with the general population, with SIRs of 4.27 (95% CI, 2.13-8.53) after adjustment for sex, age, and calendar year and of 3.50 (95% CI, 1.75-7.01) after further adjustment for mother's age (<29 years vs ≥29 years) and education (high school vs after high school). Conclusions and Relevance: In this nationwide study, having a sibling who died of SIDS was associated with a 4-fold higher risk of SIDS compared with the general population. Shared genetic and/or environmental factors may contribute to the observed clustering of SIDS. The family history of SIDS should be considered when assessing SIDS risk in clinical settings. A multidisciplinary genetic evaluation of families with SIDS could provide additional evidence.

Antirheumatic treatment, disease activity and risk of Staphylococcus aureus bacteraemia in rheumatoid arthritis: a nationwide nested case-control study.

OBJECTIVES: To assess how biological disease-modifying antirheumatic drugs (bDMARDs), glucocorticoids and disease activity affect risk of Staphylococcus aureus bacteraemia (SAB) in patients with rheumatoid arthritis (RA). METHODS: In a nationwide cohort of patients with RA from the DANBIO registry, we conducted a nested case-control study including first-time microbiologically verified SAB cases from 2010 to 2018 and incidence density matched controls (1:4 by sex, age). We interlinked Danish registries and identified antirheumatic treatments, RA-specific clinical characteristics, comorbidities and socioeconomic status. The relative risk of SAB was assessed by adjusted ORs with 95% CIs and number needed to harm (NNH) reflected the absolute risk. RESULTS: Among 30 479 patients, we identified 180 SAB cases (incidence rate: 106.7/100 000 person-years) and matched 720 controls (57% women, median age 73 years, IQR: 65-80). Risk of SAB was increased in current (OR 1.8 (95% CI 1.1 to 3.2)) and former bDMARD users (OR 2.5 (95% CI 0.9 to 7.0)), and in current users of oral glucocorticoids ≤7.5 prednisolone-equivalent mg/day (OR 2.2 (95% CI 1.3 to 4.0) and >7.5 mg/day (OR 9.5 (95% CI 3.9 to 22.7)) (non-use as reference). ORs for moderate/high disease activity compared with remission were 1.6 (95% CI 0.8 to 3.3)/1.5 (95% CI 0.6 to 4.3). Risk was increased in patients with longstanding RA (>10 years vs ≤3 years, OR=2.4 (95% CI 1.1 to 5.3)). The NNH was 1172(95% CI 426 to 9374) for current use of bDMARDs and 110(95% CI 43 to 323) for glucocorticoids >7.5 mg/day. CONCLUSION: We identified a dose-dependent increased risk of SAB in patients with RA currently using oral glucocorticoids. Daily use of >7.5 mg appeared to be a clinically relevant risk factor, whereas the absolute risk was low for bDMARDs. No clear impact of disease activity was found.

Valve regurgitation in patients surviving endocarditis and the subsequent risk of heart failure.

BACKGROUND: Significant valve regurgitation is common in patients surviving native valve infective endocarditis (IE), however the associated risk of heart failure (HF) subsequent to hospital discharge after IE is sparsely described. METHODS: We linked data from the East Danish Endocarditis Registry with administrative registries from 2002 to 2016 and included patients treated medically for IE who were discharged alive. Left-sided valve regurgitation was assessed by echocardiography at IE discharge and examined for longitudinal risk of HF. Multivariable adjusted Cox analysis was used to assess the associated risk of HF in patients with regurgitation (moderate or severe) compared with patients without regurgitation. RESULTS: We included 192 patients, 87 patients with regurgitation at discharge (30 with aortic regurgitation and 57 with mitral regurgitation) and 105 patients without. The cumulative risk of HF at 5 years of follow-up was 28.7% in patients with regurgitation at IE discharge and 12.4% in patients without regurgitation; the corresponding multivariable adjusted HR was 3.53 (95% CI 1.72 to 7.25). We identified an increased associated risk of HF for patients with aortic regurgitation (HR=2.91, 95% CI 1.14 to 7.43) and mitral regurgitation (HR=3.95, 95% CI 1.80 to 8.67) compared with patients without regurgitation. During follow-up, 21.9% and 5.7% underwent left-sided valve surgery among patients with and without regurgitation. CONCLUSION: In patients surviving IE, treated medically, we observed that severe or moderate left-sided native valve regurgitation was associated with a significantly higher risk of HF compared with patients without regurgitation at IE discharge. Close monitoring of these patients is needed to initiate surgery timely.

Risk factors for Staphylococcus aureus bacteremia in patients with rheumatoid arthritis and incidence compared with the general population: protocol for a Danish nationwide observational cohort study.

INTRODUCTION: Staphylococcus aureus bacteremia (SAB) is an invasive infection with high mortality and morbidity. Rheumatoid arthritis (RA) is associated with increased risk of infections due to the disease per se and the use of antirheumatic treatments. Few minor studies have previously investigated risk of SAB in patients with RA and indicated increased risk compared with the general population. This nationwide observational study aims to investigate incidence of and risk factors for SAB in adult patients with RA compared with the general population. The effect of disease characteristics (eg, joint erosions, disease duration and activity), different antirheumatic treatments and smoking on SAB risk will be evaluated. METHODS AND ANALYSIS: All adults (>18 years of age) alive and living in Denmark in 1996-2017 will be identified in The Danish Civil Registration System. Incident patients with RA are identified in the Danish National Patient Registry (DNPR) and the nationwide rheumatology registry, DANBIO, in which information on, for example, antirheumatic treatments, disease characteristics and smoking is collected prospectively in routine care. Information on comorbidities, invasive procedures and prescribed drugs are identified in the DNPR and in The Register of Medicinal Product Statistics. Socioeconomic status is evaluated in national registers on income and education. Incident cases of first-time SAB are identified in The Danish National SAB Database. All registers are linked on an individual level by unique civil registration numbers. Incidence rates and incidence rate ratios will be analysed using Poisson regression models and the impact of possible risk factors will be evaluated. ETHICS AND DISSEMINATION: All data will be handled in accordance with the General Data Protection Regulation (EU) 2016/679. No ethical approval is necessary in Denmark when handling registry data only. The results will be presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology initiative in international peer-reviewed journals and at medical conferences. TRIAL REGISTRATION NUMBER: NCT03908086.

Residual vegetation after treatment for left-sided infective endocarditis and subsequent risk of stroke and recurrence of endocarditis.

BACKGROUND: Little is known about the subsequent risk of stroke and recurrence of IE for patients surviving infective endocarditis (IE) with a residual vegetation at discharge. METHODS: Patients were consecutively included in the East Danish Endocarditis Registry from 2002 to 2012. We included patients undergoing medical treatment only during IE admission who were discharged alive. Size of residual vegetation was assessed by echocardiography at discharge and patients were categorized according to median length of residual vegetation. Using multivariable adjusted Cox Proportional hazard analysis, we assessed the associated risk of stroke and recurrence of IE between study groups. RESULTS: Among 915 IE patients, 305 were included after selection criteria were applied, 151 patients without residual vegetation, 73 patients with 1-5 mm residual vegetation, and 81 patients with >5 mm residual vegetation. We identified an increased associated risk of stroke for patients with 1-5 mm and > 5 mm residual vegetation, HR = 0.88 (95% CI: 0.26-2.94) and HR = 2.95 (95% CI:1.18-7.34) compared with patients without residual vegetation. No difference was seen between groups for the associated risk of recurrence of IE, HR = 1.39 (95% CI: 0.91-2.13) and HR = 1.38 (95% CI: 0.91-2.10) for patients with a residual vegetation 1-5 mm and > 5 mm compared with patients without residual vegetation. CONCLUSIONS: Patients surviving IE with a residual vegetation > 5 mm had an increased associated risk of stroke compared with patients without residual vegetation. These findings provide new perspectives on a patient group sparsely describe, suggesting a potential benefit of therapy among patients surviving IE with a residual vegetation > 5 mm.

Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment: a nationwide population-based study.

OBJECTIVES: It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization. METHODS: Using Danish administrative registries, we identified patients admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group. RESULTS: We identified 5576 patients: 4220 patients belonged to the medically treated group and 1356 patients to the surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6% in the medically treated group and the surgery group, respectively. Cardiovascular disease was the most frequent cause of death in both groups accounting for 52.5% in the medically treated group and 55.2% in the surgery group. Patients undergoing surgery were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients [hazard ratio = 0.66 (95% confidence interval: 0.46-0.94) and hazard ratio = 0.59 (95% confidence interval: 0.37-0.96), respectively]. CONCLUSIONS: No major differences were found in the main causes of death between groups. Patients in the surgical group were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients.