Role of age and comorbidities in mortality of patients with infective endocarditis.

PURPOSE: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. METHODS: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. RESULTS: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. CONCLUSION: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group.

Left endocarditis, changes in the new millennium. / Endocarditis infecciosas izquierdas, cambios con el nuevo milenio.

INTRODUCTION: a description of infective left endocarditis at the turn of the millennium. METHOD: A multicentre prospective study into the left endocarditis using data collected from the Andalusian cohort for the study of cardiovascular infections during 1984-2014. RESULTS: Of the 1,604 endocarditis cases collected, 382 belonged to G1 (group-1, period 1983-1999) and 1,222 to G2 (group-2, 2000-2014). Patients in the new millennium have a significantly higher mean age, have more comorbidity and concomitant diseases, and nosocomial and health-related endocarditis are more frequent, as well as complications. An increase in methicillin-resistant Staphylococcus aureus, Enterococcus sp., Gram-negative bacilli and Streptococcus bovis was noted. Regarding treatment, there is an increase in the use of cephalosporins and a decrease in penicillins; there is more surgery when admitted to hospital and less delay. Mortality stands at around 30% in both millennia. In the multivariate analysis, mortality was associated with: previous millennium (G1), age, Charlson index, renal failure and septic shock, and aetiologically with Staphylococcus aureus. CONCLUSIONS: Mortality remains stable, despite diagnostic and therapeutic improvements, because patients are older, have greater comorbidity, a closer relationship with the health care system (nosocomial) and microorganisms are more aggressive.

Gentamicin may have no effect on mortality of staphylococcal prosthetic valve endocarditis.

PURPOSE: To analyze the influence of adding gentamicin to a regimen consisting of ß-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). METHODS: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on ß-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. RESULTS: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84-11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03-6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29-3.38) in the multivariable analysis. CONCLUSIONS: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Infective endocarditis in patients with bicuspid aortic valve: Clinical characteristics, complications, and prognosis. / Endocarditis infecciosa sobre válvula aórtica bicúspide: características clínicas, complicaciones y pronóstico.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. It is associated to a higher risk of cardiovascular complications, including infective endocarditis (IE). METHODS: Retrospective, observational and single centre study that included all patients with IE diagnosed between 1996 and 2014. An analysis was made of the epidemiological, clinical, microbiological and echocardiographic data, complications during hospital admission, need for surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on prosthetic valves or other locations were excluded, as well as those for which the aortic valve morphology had not been accurately defined. A comparative statistical analysis was performed between BAV and tricuspid (TAV). RESULTS: Of a total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%) of them being BAV. The BAV cases were younger than TAV (51±19.06 vs. 60.83±15.73 years, P=.021) and they had less comorbidity (Charlson 0.67±0.77 vs. 1.44±1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9 vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%, P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64, P=.001). Patients with BAV had more surgery during their admission (83.3 vs. 44.1%, P=.004), had less in-hospital mortality, with no statistical significance (5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs 69.3%, P=.048). CONCLUSIONS: Patients with IE on BAV are young, with low comorbidity. They frequently present with peri-valvular complications and they often require early surgery. Compared to TAV cases, in-hospital mortality is lower and 1-year survival is significantly higher.

Endocarditis in patients with ascending aortic prosthetic graft: a case series from a national multicentre registry.

OBJECTIVES: Endocarditis in patients with ascending aortic prosthetic graft (AAPG) is a life-threatening complication. The purpose of this study was to examine the clinical presentation and prognosis of patients with AAPG endocarditis included in a large prospective infectious endocarditis multicentre study. METHODS: From January 2008 to April 2015, 3200 consecutive patients with infectious endocarditis according to the modified Duke criteria, were prospectively included in the 'Spanish Collaboration on Endocarditis Registry (GAMES)' registry. Twenty-seven definite episodes of endocarditis (0.8%) occurred in patients with AAPG. RESULTS: During the study period, 27 cases of endocarditis were detected in patients with AAPG. The median age of patients was 61 years [interquartile range (IQR) 51-68 years] and 23 (85.2%) patients were male. The median time from AAPG surgery to the episode of AAPG infection was 24 months (IQR 6-108 months). The most frequently isolated micro-organisms were coagulase-negative staphylococci and S. aureus (11 patients, 40.7%). Four patients (14.8%) underwent medical treatment, whereas surgery was performed in 21 (77.7%). Two patients (7.4%) died before surgery could be performed. The median hospital stay prior to surgery was 7 days (IQR 4-21 days). Surgery consisted of replacing previous grafts with a composite aortic graft (10 cases) or aortic homograft (2 patients), and removal of a large vegetation attached to the valve of a composite tube (1 case). Nine patients had an infected aortic valve prosthesis without evidence of involvement of the AAPG. Isolated redo-aortic valve replacement was performed in 8 (88.9%) of these patients. Reinfection occurring during 1 year of follow-up was not detected in any patient. Two patients (7.4%) died while awaiting surgery and 6 did so after surgery (22.2%). A New York Heart Association (NYHA) Class IV was associated with mortality in patients undergoing surgery (P < 0.019). CONCLUSIONS: Most cases of endocarditis in patients with AAPG occur late after initial surgery. Mortality rate of patients with AAPG endocarditis who undergo surgery is acceptable. NYHA Class IV before surgery is associated with an increased postoperative mortality.

Incidence and clinical impact of infective endocarditis after transcatheter aortic valve implantation.

AIMS: To describe the characteristics of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: This study was performed using the GAMES database, a national prospective registry of consecutive patients with IE in 26 Spanish hospitals. Of the 739 cases of IE diagnosed during the study, 1.3% were post-TAVI IE, and these 10 cases, contributed by five centres, represented 1.1% of the 952 TAVIs performed. Mean age was 80 years. All valves were implanted transfemorally. IE appeared a median of 139 days after implantation. The mean age-adjusted Charlson comorbidity index was 5.45. Chronic kidney disease was frequent (five patients), as were atrial fibrillation (five patients), chronic obstructive pulmonary disease (four patients), and ischaemic heart disease (four patients). Six patients presented aortic valve involvement, and four only mitral valve involvement; the latter group had a higher percentage of prosthetic mitral valves (0% vs. 50%). Vegetations were found in seven cases, and four presented embolism. One patient underwent surgery. Five patients died during follow-up: two of these patients died during the admission in which the valve was implanted. CONCLUSIONS: IE is a rare but severe complication after TAVI which affects about 1% of patients and entails a relatively high mortality rate. IE occurred during the first year in nine of the 10 patients.

Valve surgery in active infective endocarditis: a simple score to predict in-hospital prognosis.

AIMS: Surgery for infective endocarditis (IE) is associated with high mortality. Our objectives were to describe the experience with surgical treatment for IE in Spain, and to identify predictors of in-hospital mortality. METHODS: Prospective cohort of 1000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. RESULTS: Surgery was performed in 437 patients (43.7%). Patients treated with surgery were younger and predominantly male. They presented fewer comorbid conditions and more often had negative blood cultures and heart failure. In-hospital mortality after surgery was lower than in the medical therapy group (24.3 vs 30.7%, p=0.02). In patients treated with surgery, endocarditis involved a native valve in 267 patients (61.1%), a prosthetic valve in 122 (27.9%), and a pacemaker lead with no clear further valve involvement in 48 (11.0%). The most common aetiologies were Staphylococcus (186, 42.6%), Streptococcus (97, 22.2%), and Enterococcus (49, 11.2%). The main indications for surgery were heart failure and severe valve regurgitation. A risk score for in-hospital mortality was developed using 7 prognostic variables with a similar predictive value (OR between 1.7 and 2.3): PALSUSE: prosthetic valve, age ≥ 70, large intracardiac destruction, Staphylococcus spp, urgent surgery, sex [female], EuroSCORE ≥ 10. In-hospital mortality ranged from 0% in patients with a PALSUSE score of 0 to 45.4% in patients with PALSUSE score >3. CONCLUSIONS: The prognosis of IE surgery is highly variable. The PALSUSE score could help to identify patients with higher in-hospital mortality.

Influence of a multidisciplinary alert strategy on mortality due to left-sided infective endocarditis.

INTRODUCTION AND OBJECTIVES: Mortality from left-sided infective endocarditis remains very high. The aim of this study was to assess the impact of a multidisciplinary alert strategy (AMULTEI), based on clinical, echocardiographic and microbiological findings, implemented in 2008 in a tertiary hospital. METHODS: Cohort study comparing our historical data series (1996-2007) with the number of patients diagnosed with left-sided endocarditis from 2008-2011 (AMULTEI). RESULTS: The AMULTEI cohort included 72 patients who were compared with 155 patients in the historical cohort. AMULTEI patients were significantly older (62.5 vs 57.9 years in the historical cohort; P=.047) and had higher comorbidity (Charlson index, 3.33 vs 2.58 in the historical cohort; P=.023). There was also a trend toward more enterococcal etiology in the AMULTEI group (20.8% vs 11.6% in the historical cohort; P=.067). In the AMULTEI group, early surgery was more frequently performed (48.6% vs 23.2%; P<.001) during hospitalization, the incidence of septic shock was significantly lower (9.7% vs 24.5%; P=.009) and there was a trend toward reductions in neurological complications (19.4% vs 29.0%; P=.25) and severe heart failure (12.5% vs 18.7%; P=.24). In-hospital mortality and mortality during the first month of follow-up were significantly lower in the AMULTEI group (16.7% vs 36.1%; P=.003). CONCLUSIONS: Despite the trend toward older age and more comorbidity measured by the Charlson index, early mortality was significantly lower in patients treated with the AMULTEI strategy.

Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study.

BACKGROUND: The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. METHODS AND RESULTS: This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P<0.01), although only moderate to severe ischemic stroke (HR 1.63) and brain hemorrhage (HR 1.73) were significantly associated with a poorer prognosis. Antimicrobial treatment reduced (by 33% to 75%) the risk of neurological complications. In patients with hemorrhage, mortality was higher when surgery was performed within 4 weeks of the hemorrhagic event (75% versus 40% in later surgery). CONCLUSIONS: Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.

Natural history of compensated hepatitis C virus-related cirrhosis in HIV-infected patients.

OBJECTIVE: To provide information about the incidence and predictors of liver decompensation and death due to liver failure in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: Prospective cohort study of 154 HIV-HCV-coinfected patients with a new diagnosis of Child-Pugh-Turcotte (CPT) class A compensated cirrhosis. We evaluated time from diagnosis to the first liver decompensation and death from liver disease, as well as predictors of these outcomes. RESULTS: Thirty-six patients (23.4%) developed liver decompensation. The incidence of liver decompensation was 6.40 cases per 100 person-years (95% confidence interval [CI], 4.18-9.38 cases per 100 person-years). Factors independently associated with liver decompensation were lack of HCV therapy (hazard ratio [HR], 3.38; 95% CI, 1.09-10.53; P = .035), baseline CD4 cell counts

[Enterococcal endocarditis: a multicenter study of 76 cases]. / Endocarditis por enterococo: análisis multicéntrico de 76 casos.

BACKGROUND: Although enterococci occupy the third position among microorganisms producing infectious endocarditis (IE) following streptococci and Staphylococcus aureus, few multicenter studies have provided an in-depth analysis of enterococcal IE. METHODS: Description of the characteristics of 76 cases of enterococcal left-sided infectious endocarditis (LSIE) (native: 59, prosthetic: 17) retrieved from the database of the Cardiovascular Infections Study Group of the Andalusian Society of Infectious Diseases, with emphasis on the comparison with non-enterococcal LSIE. RESULTS: Enterococci were the causal agent in 76 of the 696 episodes of LSIE (11%). Compared with non-enterococcal LSIE, enterococcal LSIE was more commonly seen in patients older than 65 (47.4% vs. 27.6%, P<0.0005), and those with chronic diseases (75% vs. 54.6%, P<0.001), calcified valves (18.6% vs. 10%, P<0.05), and previous urinary (30.3% vs. 2.1%, P<0.00001) or abdominal (10.5% vs. 3.1%, P<0.01) infections, and produced a higher rate of relapses (6.6% vs. 2.3%, P<0.05). Enterococcal LSIE was associated with fewer peripheral vascular or skin manifestations (14.5% vs. 27.1%, P<0.05) and fewer immunological phenomena (10.5% vs. 24%, P<0.01). Among the total of patients with enterococcal LSIE, 36.8% underwent valve surgery during hospitalization. In-hospital mortality was 32.9% for enterococcal LSIE, 9.3% for viridans group streptococci (VGS) LSIE and 48.6% for S. aureus LSIE (enterococci vs VGS: P<0.0001; enterococci vs S. aureus: P=0.02). Enterococcal LSIE patients treated with the combination of a penicillin or vancomycin plus an aminoglycoside (n=60) and those treated with ampicillin plus ceftriaxone (n=6) showed similar in-hospital mortality (26.7% vs 33.3%, P=0.66). High-level resistance to gentamicin was detected in 5 of 38 episodes of enterococcal LSIE (13.1%). CONCLUSIONS: Enterococcal LSIE appears in patients with well-defined clinical characteristics, and causes few peripheral vascular or skin manifestations and few immunological phenomena. The relapse rate is higher than in non-enterococcal LSIE. Mortality due to enterococcal LSIE is lower than that of S. aureus LSIE, and much higher than that of VGS LSIE. Mortality due to enterococcal LSIE is similar in patients treated with ampicillin plus ceftriaxone or with a combination of penicillin or vancomycin plus an aminoglycoside. High-level resistance to gentamicin remains uncommon in enterococci causing LSIE.

Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy.

UNLABELLED: Little is known about the natural history of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects under highly active antiretroviral therapy (HAART). The objectives of this study were to obtain information about the mortality, the incidence of hepatic decompensations, and the predictors thereof in this population. In a multicenter cohort study, the time to the first hepatic decompensation and the survival of 1,011 antiretroviral naïve, HIV/HCV-coinfected patients who started HAART and who were followed prospectively were analyzed. After a median (Q1-Q3) follow-up of 5.3 (2.9-7.1) years, 59(5.83%) patients developed a hepatic decompensation and 69 (6.82%) died, 30 (43%) of them because of liver disease. The factors independently associated [HR (95% CI)] with the occurrence of hepatic decompensations were age older than 33 years [2.11 (1.18-3.78)], female sex [2.11 (1.07-4.15)], Centers for Disease Control stage C [2.14 (1.24-3.70)], a diagnosis of cirrhosis at baseline [10.86 (6.02-19.6)], CD4 cell gain lower than 100/mm3 [4.10 (2.18-7.69)] and less than 60% of the follow-up with undetectable HIV viral load [5.23 (2.5-10.93)]. Older age [2.97 (1.18-7.50)], lack of HCV therapy [11.32 (1.44-89.05)], hepatitis D virus coinfection [16.15 (2.45-106.48)], a diagnosis of cirrhosis at recruitment [13.69 (5.55-34.48)], hepatic encephalopathy [62.5 (21.27-200)] and lower CD4 cell gain [3.63 (1.45-9.09)] were associated with mortality due to liver failure. CONCLUSION: End-stage liver disease is the primary cause of death in HIV/HCV-coinfected patients under HAART. Higher increase of CD4 cell counts, lack of markers of serious liver disease and therapy against HCV are factors associated with better hepatic outcome.

Efavirenz trough levels are not associated with virological failure throughout therapy with 800 mg daily and a rifampicin-containing antituberculosis regimen.

OBJECTIVES: To assess the safety and efficacy of efavirenz 800 mg daily in HIV-infected patients with tuberculosis receiving a rifampicin-containing regimen and to analyse whether a relationship exists between efavirenz Cmin and its virological efficacy. METHODS: Prospective, open-labelled study including HIV-infected patients on rifampicin and efavirenz 800 mg daily. Treatment adherence, adverse events (AEs), HIV-RNA levels, CD4 cell counts and efavirenz Cmin during and after finishing rifampicin treatment were evaluated. RESULTS: Eighty patients met the inclusion criteria. A permanent drug withdrawal due to AEs occurred in 10 patients, 5 attributable to efavirenz, and 10 patients were lost to follow-up before the third month. Efavirenz Cmin levels with 800 mg plus rifampicin were similar to those with 600 mg after withdrawing rifampicin. Sixty patients were included in the efficacy analysis, eight experiencing virological failure. No relation was observed between the rate of virological failure and efavirenz Cmin, previous antiretroviral treatment or not, baseline CD4 counts or RNA-HIV. The only variable related to virological failure was irregular adherence [odds ratio, 81 (95% CI: 5-1280); P=0.002]. CONCLUSIONS: Given the lack of a demonstrated relationship between efavirenz Cmin and its efficacy in our study, a firm recommendation cannot be made to always increase the dose to 800 mg/day when concomitantly given with rifampicin, but it seems a cautious approach to maintain the same efavirenz plasma levels as with 600 mg daily without rifampicin. Patients weighing<55 kg and also black, Asian and Hispanic subjects in whom genetic-based increased efavirenz plasma levels and rates of AEs have been observed may benefit from a dose of 600 mg.