Dissecting the correlates of N-terminal prohormone brain natriuretic peptide in acute infective endocarditis.

PURPOSE: To explore the prognostic value and the correlates of NT-proBNP in patients with acute infective endocarditis, a life-threatening disease, with an often unpredictable outcome given by the lack of reliable prognostic parameters. METHODS: We retrospectively studied 337 patients admitted to our centre between January 1, 2006 and September 30, 2020 with available NT-proBNP level at admission. Our analyses were performed considering NT-proBNP as both a categorical variable, using the median value as the cut-off level, and numerical variable. Study end points were in-hospital mortality, cardiac surgery and 1 year survival. RESULTS: NT-proBNP was an independent predictor of in-hospital mortality (OR 14.9 [95%C.I. 2.46-90.9]; P = .003). Levels below 2926 pg/mL were highly predictive of a favorable in-hospital outcome (negative predictive value 96.6%). Patients with higher NT-proBNP levels showed a significantly lower survival rate at 1 year follow-up (log-rank P = .005). NT-proBNP was strongly associated with chronic kidney disease (P < .001) and significantly higher in patients with prior chronic heart failure (P = .001). NT-proBNP was tightly related to staphylococcal IE (P = .001) as well as with higher CRP and hs-troponin I (P = 0.023, P < .001, respectively). CONCLUSION: Our results confirm the remarkable prognostic role of NT-proBNP in patients with IE and provide novel evidences of its multifaceted correlates in this unique clinical setting. Our data strongly support the incorporation of NT-proBNP into the current diagnostic work-up of IE.

Prognostic value of pro-adrenomedullin and copeptin in acute infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a life-threatening disease whose prognosis is often difficult to predict based on clinical data. Biomarkers have been shown to favorably affect disease management in a number of cardiac disorders. Aims of this retrospective study were to assess the prognostic role of procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and copeptin in IE and their relation with disease characteristics and the traditional biomarker C-reactive protein (CRP). METHODS: We studied 196 patients with definite IE. Clinical, laboratory and echocardiography parameters were analyzed, with a focus on co-morbidities. PCT, pro-ADM and copeptin were measured on stored plasma samples obtained on admission during the acute phase of the disease. RESULTS: Pro-ADM and copeptin were significantly higher in older patients and associated with prior chronic kidney disease. Pro-ADM was an independent predictor of hospital mortality (OR 3.29 [95%C.I. 1.04-11.5]; p = 0.042) whilst copeptin independently predicted 1-year mortality (OR 2.55 [95%C.I. 1.18-5.54]; p = 0.017). A high PCT value was strictly tied with S. aureus etiology (p = 0.001). CRP was the only biomarker associated with embolic events (p = 0.003). CONCLUSIONS: Different biomarkers correlate with distinct IE outcomes. Pro-ADM and copeptin may signal a worse prognosis of IE on admission to the hospital and could be used to identify patients who need more aggressive treatment. CRP remains a low-cost marker of embolic risk. A high PCT value should suggest S. aureus etiology.

Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli: Data from the Prospective Multicenter Italian Endocarditis Study Cohort.

The objective of this study was to investigate predisposing factors and outcomes of infective endocarditis (IE) caused by non-HACEK Gram-negative bacilli (GNB) in a contemporary multicenter cohort. Patients with IE due to GNB, prospectively observed in 26 Italian centers from 2004 to 2011, were analyzed. Using a case-control design, each case was compared to three age- and sex-matched controls with IE due to other etiologies. Logistic regression was performed to identify risk factors for IE due to GNB. Factors associated with early and late mortality were assessed by Cox regression analysis. The study group comprised 58 patients with IE due to GNB. We found that Escherichia coli was the most common pathogen, followed by Pseudomonas aeruginosa and Klebsiella pneumoniae The genitourinary tract as a source of infection (odds ratio [OR], 13.59; 95% confidence interval [CI], 4.63 to 39.93; P < 0.001), immunosuppression (OR, 5.16; 95% CI, 1.60 to 16.24; P = 0.006), and the presence of a cardiac implantable electronic device (CIED) (OR, 3.57; 95% CI, 1.55 to 8.20; P = 0.003) were factors independently associated with IE due to GNB. In-hospital mortality was 13.8%, and mortality rose to 30.6% at 1 year. A multidrug-resistant (MDR) etiology was associated with in-hospital mortality (hazard ratio [HR], 21.849; 95% CI, 2.672 to 178.683; P = 0.004) and 1-year mortality (HR, 4.408; 95% CI, 1.581 to 12.287; P = 0.005). We conclude that the presence of a genitourinary focus, immunosuppressive therapy, and an indwelling CIED are factors associated with IE due to GNB. MDR etiology is the major determinant of in-hospital and long-term mortality.

Prognostic Value of Decreased High-Density Lipoprotein Cholesterol Levels in Infective Endocarditis.

(1) Background: Simple parameters to be used as early predictors of prognosis in infective endocarditis (IE) are lacking. The aim of this study was to evaluate the prognostic role of high-density-lipoprotein cholesterol (HDL-C) and also of total-cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and triglycerides, in relation to clinical features and mortality, in IE. (2) Methods: Retrospective analysis of observational data from 127 consecutive patients with a definite diagnosis of IE between 2016 and 2019. Clinical, laboratory and echocardiography data, mortality, and co-morbidities were analyzed in relation to HDL-C and lipid profile. (3) Results: Lower HDL-C levels (p = 0.035) were independently associated with in-hospital mortality. HDL-C levels were also significantly lower in IE patients with embolic events (p = 0.036). Based on ROC curve analysis, a cut-off value was identified for HDL-C equal to 24.5 mg/dL for in-hospital mortality. HDL-C values below this cut-off were associated with higher triglyceride counts (p = 0.008), higher prevalence of S. aureus etiology (p = 0.046) and a higher in-hospital mortality rate (p = 0.004). Kaplan-Meier survival analysis showed higher 90-day mortality in patients with HDL-C ≤ 24.5 mg/dL (p = 0.001). (4) Conclusions: Low HDL-C levels could be used as an easy and low-cost marker of severity in IE, particularly to predict complications, in-hospital and 90-day mortality.

Long-Term Outcome of Infective Endocarditis Involving Cardiac Implantable Electronic Devices: Impact of Comorbidities and Lead Extraction.

(1) Background: Management of cardiac implantable electronic device-related infective endocarditis (CIED-IE) hinges on complete hardware removal. We assessed whether long-term prognosis is affected by device removal, considering baseline patient comorbid conditions; (2) Methods: A total of 125 consecutive patients hospitalized for CIED-IE were included in this retrospective analysis. Outcomes were in-hospital, one-year, and long-term mortality. There were 109 patients who underwent device removal, 91 by transvenous lead extraction (TLE) and 18 by open heart surgery (OHS); (3) Results: TLE translated into lower hospital mortality (4.4% vs. 22.5% with OHS; p = 0.03). Septic pulmonary embolism was the only independent predictor of in-hospital mortality (OR:7.38 [1.49-36.6], p = 0.013). One-year mortality was in contrast independently associated to tricuspid valve involvement (p = 0.01) and Charlson comorbidity index (CCI, p = 0.039), but not the hardware removal modality. After a median follow-up of 41 months, mortality rose to 24%, and was significantly influenced only by CCI. Specifically, patients with a higher CCI who were also treated with TLE showed a survival rate not significantly different from those managed with medical therapy only; (4) Conclusions: In CIED-IE, TLE is the strategy of choice for hardware removal, improving early outcomes. Long-term benefits of TLE are lessened by comorbidities. In cases of CIED-IE with high CCI, a more conservative approach might be an option.

Dalbavancin for infective endocarditis: a single centre experience.

Infective endocarditis (IE) is a life-threatening disease, mostly caused by gram-positive cocci, needing a 4-6 weeks antibiotic course. Dalbavancin is a lipoglycopeptide active on gram-positive microorganisms, with a unique pharmacokinetic profile. We describe our experience with dalbavancin to complete the intravenous antibiotic regimen for difficult-to-treat IE cases due to gram-positive bacteria. We treated 10 severely ill patients, each presenting several comorbidities. Seven patients were microbiologically cured from IE, but two patients experienced IE relapse due to the same microrganism. Short-term mortality after dalbavancin was nil, but late mortality (within 1 year of hospital discharge) was 60%. No death was related to dalbavancin therapy. Treatment was generally well tolerated. Dalbavancin may be an option to complete IE treatment in selected cases, once blood culture clearance and improvement of clinical conditions under standard therapy is reached, allowing shortening of hospitalization.

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Clinical Significance and Prognostic Value of Hemostasis Parameters in 337 Patients with Acute Infective Endocarditis.

(1) Background: The aim of this study was to assess the clinical significance and prognostic role of the main hemostasis parameters in infective endocarditis (IE): prothrombin time as international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, platelet count, homocysteine. (2) Methods: We studied 337 patients with IE. Clinical, hemato-chemical and echocardiography parameters were analyzed. Coagulation parameters were measured on admission. (3) Results: D-dimers levels (p = 0.012) and a prolonged PT-INR (p = 0.013) were associated with higher in-hospital mortality, while prolonged aPTT (p = 0.021) was associated with increased 1-year mortality. Staphylococcus aureus (S. aureus) infection (p = 0.003), prosthetic valve endocarditis (PVE) (p = 0.001), surgical indication (p = 0.002) and higher D-dimer levels (p = 0.005) were independent predictors of in-hospital mortality. PVE (p = 0.001), a higher Charlson Comorbidity Index (p = 0.049), surgical indication (p = 0.001) and prolonged aPTT (p = 0.012) were independent predictors of 1-year mortality. Higher levels of D-dimers (p < 0.001) and a shorter aPTT (p < 0.001) were associated with embolic complications of IE. S. aureus etiology was bound to higher D-dimers levels (p < 0.001) and a shorter aPTT (p = 0.006). (4) Conclusions: Elevated D-dimers are associated with a higher risk for in-hospital mortality in IE patients. High D-dimers and a short aPTT are associated with a higher risk for embolic events in IE. A longer aPTT is associated with 1-year mortality.

Predictors of long-term mortality in left-sided infective endocarditis: an historical cohort study in 414 patients.

INTRODUCTION: Very limited data are available on the long-term outcome of infective endocarditis (IE) and its determinants. The aim of this study was to identify the predictors of long-term mortality in patients affected by left sided IE (LSIE). METHODS: This was an historical retrospective observational study on prospectively collected data from patients with LSIE hospitalized in our Unit (January 2000-December 2017). Multiple variables relevant to history, physical examination, laboratory tests, echocardiography, comorbidities, complications and outcome were analysed by Cox regression to identify predictors of long-term mortality. RESULTS: 414 patients were included, and followed up for a median of 39 months [IQR 11-74]. Median age was 59 years [range 3-89], and most patients were male. Over 50% showed at least one comorbidity. Hyperglycaemia, increased creatinine and an indication for surgery predicted in-hospital mortality, while a prior myocardial infarction, chronic kidney disease (CKD) on hemodialysis and a larger vegetation were independent predictors of 1-year mortality. At multivariate analysis, peripheral arterial disease (p= 0.017), hyperglycemia on admission (p=0.013) and a higher BMI (p=0.009) were independent predictors of long-term mortality in 1-year survivors. At multivariable Cox proportional hazard regression, peripheral arterial disease (p=0.002), hyperglycemia (p=0.041) and CKD on hemodialysis (p=0.025) confirmed to be independently associated with an increased risk of long-term mortality in the overall 414 patient cohort. CONCLUSIONS: Cardiovascular and metabolic risk signals, specifically peripheral arterial disease and hyperglicemia, affect long-term mortality of LSIE. An active and long-term follow up seems warranted in IE survivors showing these conditions at outset.

Enterococcal infective endocarditis is a marker of current occult or future incident colorectal neoplasia.

BACKGROUND: Few studies suggest an association between Enterococcal infective endocarditis (EIE) and colorectal disease, including colorectal neoplasia (CRN) and colorectal cancer (CRC). In this study, we analyze differences in prevalence, risk factors and outcome of CRN and CRC between EIE and Streptococcus gallolyticus infective endocarditis (SGIE). METHODS: Single center, observational study of 166 patients with definite EIE or SGIE. Clinical data were collected prospectively in a standardized IE protocol. Colonoscopy data were collected retrospectively on 90 patients. RESULTS: 85 patients had EIE, 81 SGIE. EIE patients had a higher rate of prior cancer (20% vs 6%) and health-care associated infection (12% vs 1%), but similar mortality than SGIE. Colonoscopy performed in 90 patients showed intestinal diseases in 30 of 42 (71%) EIE patients vs. 40 of 48 (83%) SGIE patients (p = 0.174), with a predominance of CRN. Among 78 patients who underwent colonoscopy after IE diagnosis, no difference between EIE and SGIE was observed in the rate of non-neoplastic lesions (48% vs 47%), benign (32% vs 40%) or malignant (13% vs 15%) neoplastic lesions. Adverse events during colonoscopy were uncommon, although a careful handling of anticoagulation was required. CONCLUSIONS: EIE seems to be associated with colorectal disease, including colorectal neoplasia and colorectal cancer, to the same extent as SGIE. EIE should be considered a marker of colorectal neoplasia, even in patients with a clear health-care related acquisition. Colonoscopy is generally safe in EIE patients, and should be considered to early diagnose and treat colorectal disease.

Real-life experience with ceftobiprole in a tertiary-care hospital.

OBJECTIVES: Ceftobiprole is a new therapeutic option for bacterial pneumonia, with activity against most antimicrobial-resistant Gram-positive cocci, including methicillin-resistant Staphylococcus aureus. Data on the use of ceftobiprole in real life are limited. We evaluated the efficacy and safety of ceftobiprole in a context of a hospital practice. METHODS: In a single-centre, observational, retrospective clinical study, we collected data of 29 patients undergoing ceftobiprole therapy, with a focus on clinical outcomes and adverse events. RESULTS: There was a high burden of comorbidities in the study cohort, including kidney dysfunction (38%) and cancer (24%), and a high proportion of patients with sepsis/septic shock (72%), a central line (41%) or on mechanical ventilation (21%). Most infections were nosocomial (24, 82.8%). Ceftobiprole was mostly prescribed for pneumonia (17 patients, 58.6%), and bloodstream infections (10 patients, 34.5%), both empirically (9 cases, 31%) and as targeted therapy (20, 69%, with staphylococci as the dominant pathogens). It was the first-line drug in 15 cases (51.7%). Overall, a favourable clinical outcome was observed in the majority of cases (68.9%), with clinical cure in 3 (10.3%) and clinical improvement in 17 (58.6%). Failure of treatment occurred in seven cases (24.1%). Three patients experienced a definite ceftobiprole-related adverse event, with two cases of myoclonus. No major adverse effect on bone marrow, kidney or liver function was observed. CONCLUSIONS: Ceftobiprole, even outside current indications, may be a safe and effective treatment for resistant Gram-positive cocci infections where other drugs are inactive or poorly tolerated, and for salvage therapy.

Clinical significance of hyperhomocysteinemia in infective endocarditis: A case-control study.

Blood coagulation plays a key role in the pathogenesis of infective endocarditis (IE). Conditions associated with thrombophilia could enhance IE vegetation formation and promote embolic complications.In this study, we assessed prevalence, correlates, and clinical consequences of hyper-homocysteinemia (h-Hcy) in IE.Homocysteine (Hcy) plasma levels were studied in 246 IE patients and 258 valvular heart disease (VHD) patients, as well as in 106 healthy controls.IE patients showed Hcy levels comparable to VHD patients (14.9 [3-81] vs 16 [5-50] µmol/L, respectively; P = 0.08). H-Hcy was observed in 48.8% of IE patients and 55.8% of VHD (P = 0.13). Vegetation size and major embolic complications were not related to Hcy levels. IE patients with h-Hcy had a higher prevalence of chronic kidney disease and a higher 1-year mortality (19.6% vs 9.9% in those without h-Hcy; OR 2.21 [1.00-4.89], P = 0.05). However, at logistic regression analysis, h-Hcy was not an independent predictor of 1-year mortality (OR 1.87 [95% CI 0.8-4.2]; P = 0.13).Our data suggest h-Hcy in IE is common, is related to a worse renal function, and may be a marker of cardiac dysfunction rather than infection. H-Hcy does not appear to favor IE vegetation formation or its symptomatic embolic complications.