Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.

Apixaban versus Aspirin for Embolic StrokeIn a trial of 352 patients with embolic stroke of undetermined source, 5 mg of apixaban administered twice daily was compared with 100 mg of aspirin administered once daily for the prevention of recurrent ischemic strokes. At 12 months, 13.6% of patients given apixaban had new ischemic lesions on magnetic resonance imaging compared with 16.0% of patients given aspirin, and the rates of clinically relevant bleeding were also comparable.

Platelet SR-PSOX/CXCL16-CXCR6 Axis Influences Thrombotic Propensity and Prognosis in Coronary Artery Disease.

Platelets express the transmembrane chemokine SR-PSOX/CXCL16, proteolytic cleavage of which generates the sCXCL16 soluble-(s) chemokine. The sCXCL16 engages CXCR6 on platelets to synergistically propagate degranulation, aggregation and thrombotic response. Currently, we have investigated the pro-thrombotic and prognostic association of platelet CXCL16−CXCR6 axis in CAD-(n = 240; CCS n = 62; ACS n = 178) patients. Platelet surface-associated-CXCL16 and CXCR6 surface expression ascertained by flow cytometry correlated significantly with platelet activation markers (CD62P denoting degranulation and PAC-1 binding denoting α2bß3-integrin activation). Higher platelet CXCL16 surface association (1st quartile vs. 2nd−4th quartiles) corresponded to significantly elevated collagen-induced platelet aggregation assessed by whole blood impedance aggregometry. Platelet-CXCL16 and CXCR6 expression did not alter with dyslipidemia, triglyceride, total cholesterol, or LDL levels, but higher (>median) plasma HDL levels corresponded with decreased platelet-CXCL16 and CXCR6. Although platelet-CXCL16 and CXCR6 expression did not change significantly with or correlate with troponin I levels, they corresponded with higher Creatine Kinase-(CK) activity and progressively deteriorating left ventricular ejection fraction (LVEF) at admission. Elevated-(4th quartile) platelet-CXCL16 (p = 0.023) and CXCR6 (p = 0.030) measured at admission were significantly associated with a worse prognosis. However, after Cox-PH regression analysis, only platelet-CXCL16 was ascertained as an independent predictor for all-cause of mortality. Therefore, the platelet CXCL16−CXCR6 axis may influence thrombotic propensity and prognosis in CAD patients.

C5 Variant rs10985126 is Associated with Mortality in Patients with Symptomatic Coronary Artery Disease.

BACKGROUND: Complement component 5a (C5a) is a highly potent anaphylatoxin with a variety of pro-inflammatory effects. C5a contributes to progression of atherosclerosis and inhibition of the receptor (C5aR) might offer a therapeutic strategy in this regard. Single nucleotide polymorphisms (SNPs) of the C5 gene may modify protein expression levels and therefore function of C5a and C5aR. This study aimed to examine associations between clinically relevant C5a SNPs and the prognosis of patients with symptomatic coronary artery disease (CAD). Furthermore, we sought to investigate the influence of C5 SNPs on C5aR platelet surface expression and circulating C5a levels. METHODS: C5 variants (rs25681, rs17611, rs17216529, rs12237774, rs41258306, and rs10985126) were analyzed in a consecutive cohort of 833 patients suffering from symptomatic coronary artery disease (CAD). Circulating C5a levels were determined in 116 patients whereas C5aR platelet surface expression was measured in 473 CAD patients. Endpoints included all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS). Homozygous carriers (HC) of the minor allele (rs10985126) showed significantly higher all-cause mortality than major allele carriers. While we could not find significant associations between rs10985126 allele frequency and C5aR platelet surfazl ce expression, significantly elevated levels of circulating C5a were found in HC of the minor allele of the respective genotype. rs17216529 allele frequency correlated with the composite combined endpoint and bleeding events. However, since the number of HC of the minor allele of this genotype was low, we cannot draw a robust conclusion about the observed associations. CONCLUSION: In this study, we provide evidence for the prognostic relevance of rs10985126 in CAD patients. C5 rs10985126 may serve as a prognostic biomarker for risk stratification in high-risk CAD patients and consequently promote tailored therapies.

Predicting 1-, 3- and 5-year outcomes in patients with coronary artery disease: A comparison of available risk assessment scores.

BACKGROUND AND AIMS: Thromboischemic and bleeding events are rare but life-threatening complications after percutaneous coronary intervention (PCI). Various risk assessment models have been established to predict short- and long-term adverse events in patients with chronic and acute coronary syndromes (CCS, ACS). The aim of the present study was to compare available risk assessment systems based on their performance in identifying high-risk patients with symptomatic coronary artery disease (CAD). METHODS: We enrolled 1565 consecutive patients with symptomatic CAD (n = 821 CCS, n = 744 ACS). CALIBER, DAPT, GRACE 2.0, PARIS-CTE, PARIS-MB, PRECISE-DAPT and PREDICT-STABLE scores were calculated in appropriate patient subgroups. All patients were followed-up for 1, 3 and 5 years for all-cause death (ACD), myocardial infarction (MI), ischemic stroke (IS) and bleeding. The primary combined ischemic endpoint (CE) consisted of ACD, MI and/or IS. Secondary endpoints were defined as single occurrence of either ACD, MI, IS, or bleeding. RESULTS: GRACE 2.0 score showed good discrimination performance (AUC>0.7) for CE in a 3- and 5-year follow-up. CALIBER, GRACE 2.0 and PARIS-CTE showed best performance (AUC>0.7) in predicting ACD throughout the follow-up, whereas IS was best predicted by PARIS-CTE and CALIBER scores. None of the scores performed well (AUC>0.7) in predicting MI or bleeding. CONCLUSIONS: In a consecutive German CAD cohort, CALIBER, GRACE 2.0 and PARIS-CTE scores performed best in predicting CE, ACD and/or IS whereas none of the selected scores could predict MI and bleeding efficiently.

Platelet surface expression of cyclophilin A is associated with increased mortality in patients with symptomatic coronary artery disease.

BACKGROUND: Cyclophilin A (CyPA) is an important intracellular molecule mediating essential cellular functions such as signaling and protein folding. Enhanced CyPA platelet surface expression is associated with hypertension and hypercholesterolemia in patients with stable coronary artery disease (CAD). In patients with acute myocardial infarction CyPA platelet surface expression is significantly decreased. The aim of this study was to investigate possible associations of CyPA platelet surface expression and a clinically relevant CyPA single-nucleotide polymorphism (CyPA PPIA rs6850) with prognosis in patients with symptomatic cardiovascular disease. MATERIALS AND METHODS: Blood was obtained from 335 consecutive patients with symptomatic CAD. All patients were followed up for 1080 days for endpoints all-cause death, myocardial infarction (MI), ischemic stroke, and bleeding. The primary combined endpoint was defined as a composite of all-cause death and/or MI and/or ischemic stroke. Cyclophilin A platelet surface expression levels less than or equal to the median were significantly associated with a worse prognosis (combined endpoint and all-cause death) when compared to CyPA greater than the median. Genotyping for CyPA PPIA rs6850 was performed in 752 patients with symptomatic CAD. Homozygous carriers of the minor allele showed a significantly worse cumulative event-free survival for both combined endpoint and MI when compared to carriers of the major allele. CONCLUSION: The CyPA platelet surface expression is associated with mortality whereas CyPA PPIA rs6850 is associated with recurrent MI in patients with symptomatic CAD. Cyclophilin A might offer a new biomarker for risk stratification and tailoring therapies in patients with cardiovascular disease.

Nocturnal respiratory rate as a predictor of mortality in patients with acute coronary syndrome.

Background: Patients with acute coronary syndrome (ACS) are at risk especially in the period shortly after the event. Alterations in respiratory control have been associated with adverse prognosis. The aim of our study was to assess if the nocturnal respiratory rate (NRR) is a predictor of mortality in patients with ACS presenting in the emergency department. Methods: Clinically stable consecutive patients with ACS aged ≥ 18 years were prospectively enrolled. The Global Registry of Acute Coronary Events (GRACE) score and left ventricular ejection fraction (LVEF) were assessed for all patients. The average NRR over a period of 6 hours was determined by the records of the surveillance monitors in the first night after admission. Primary and secondary endpoints were intrahospital and 2 years all-cause mortality, respectively. Results: Of the 860 patients with ACS, 21 (2.4%) died within the intrahospital phase and 108 patients (12.6%) died within the subsequent 2 years. The NRR was a significant predictor of both endpoints and was independent from the GRACE score and LVEF. Implementing the NRR into the GRACE risk model leads to a significant increase of the C-statistics especially for prediction of intrahospital mortality. Conclusion: The NRR is an independent predictor of mortality in patients with ACS.

Mitral Valve Endocarditis due to Lactobacillus.

Lactobacillus species are Gram-positive, facultative anaerobic, rod-shaped bacteria. They belong to the lactic acid bacteria group and are also known as a usual part of the normal flora of the gastrointestinal tract as well as of the urinary and genital tracts. They are an infrequent human pathogen but can induce several infections such as bacteremia and infectious endocarditis. We report the case of an 81-year-old woman with Lactobacillus bacteremia and mitral valve endocarditis as well as splenic abscesses.

Autonomic Nervous System Activity for Risk Stratification of Emergency Patients With Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) causes appreciable morbidity and mortality in adults, especially in those ≥65 years of age. At hospital admission, an immediate and reliable risk assessment is necessary to detect patients with possible fatal outcome. OBJECTIVE: We aimed to evaluate markers of the autonomic nervous system based on an electrocardiogram to predict mortality in patients with CAP. METHODS: For this purpose, the deceleration capacity (DC) of heart rate was calculated in 253 patients who presented to the emergency department with CAP. The 30-day mortality rate was defined as the primary endpoint (PEP). The secondary endpoint was the total mortality within 180 days. RESULTS: PEP was reached in 33 patients (13%). The DC, measured in milliseconds, was significantly lower in patients who reached the PEP than in those who did not (2.3 ± 1.5 ms vs. 3.6 ± 2.3 ms, p = 0.004). The DC was also significantly lower in nonsurvivors than in survivors at the time of the secondary endpoint (2.3 ± 1.5 ms vs. 3.7 ± 2.4 ms, p < 0.001). Our results indicate that DC is an independent predictor of 30- and 180-day mortality. CONCLUSION: DC was independently associated with death from CAP in our study. As a practical consequence, DC could be useful in triage decisions. Patients with certain high risks could benefit from adjuvant treatment and special medical attention.

Deceleration capacity as a risk predictor in patients presenting to the emergency department with syncope: A prospective exploratory pilot study.

Syncope is a common cause for admission to the emergency department (ED). Due to limited clinical resources there is great interest in developing risk stratification tools that allow identifying patients with syncope who are at low risk and can be safely discharged. Deceleration capacity (DC) is a strong risk predictor in postinfarction and heart failure patients. The aim of this study was to evaluate whether DC provides prognostic information in patients presenting to ED with syncope.We prospectively enrolled 395 patients presenting to the ED due to syncope. Patient's electrocardiogram (ECG) for the calculation of DC was recorded by monitoring devices which were started after admission. Both the modified early warning score (MEWS) and the San Francisco syncope score (SFSS) were determined in every patient. Primary endpoint was mortality after 180 days.Eight patients (2%) died after 180 days. DC was significantly lower in the group of nonsurvivors as compared with survivors (3.1 ±â€Š2.5 ms vs 6.7 ±â€Š2.4 ms; P < .001), whereas the MEWS was comparable in both was comparable in both groups. (2.1 ±â€Š0.8 vs 2.1 ±â€Š1.0; P = .84). The SFSS failed at identifying 4 of 8 nonsurvivors (50%) as high risk patients. No patient with a favorable DC (≥7 ms) died (0.0% vs 3.7%; P = .01, OR 0.55 (95% CI 0.40-0.76), P < .001). In the receiver operating characteristic (ROC) analysis DC yielded an area under the curve of 0.85 (95% CI 0.71-0.98).Our study demonstrates that DC is a predictor of 180-days-mortality in patients admitted to the ED due to syncope. Syncope patients at low risk can be identified by DC and may be discharged safely.

Deceleration capacity of heart rate predicts 1-year mortality of patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Risk prediction in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) is challenging. Development of novel markers for patient risk assessment is of great clinical value. Deceleration capacity (DC) of heart rate is a strong risk predictor in post-infarction patients. HYPOTHESIS: DC provides prognostic information in patients undergoing TAVI. METHODS: We enrolled 374 consecutive patients with severe AS undergoing TAVI. All patients received 24-hour Holter recording or continuous heart-rate monitoring to assess DC before intervention. Primary endpoint was all-cause mortality after 1 year. RESULTS: Forty-nine patients (13.1%) died within 1 year. DC was significantly lower in nonsurvivors than in survivors (1.2 ± 4.8 ms vs 3.3 ± 2.9 ms; P < 0.001), whereas the logistic EuroSCORE and EuroSCORE II were comparable between groups (logistic EuroSCORE: 27.3% ± 17.0% vs 22.9% ± 14.2%; P = 0.122; EuroSCORE II: 8.0% ± 6.9% vs 6.7% ± 4.8%, P = 0.673). One-year mortality in the 116 patients with impaired DC (<2.5 ms) was significantly higher than in patients with normal DC (23.3% vs 8.5%; P < 0.001). In multivariate Cox regression analysis that included DC, sex, paroxysmal atrial fibrillation, hemoglobin level before TAVI, and logistic EuroSCORE, DC was the strongest predictor of 1-year mortality (hazard ratio: 0.88, 95% confidence interval: 0.85-0.94, P < 0.001). DC yielded an AUC in the ROC analysis of 0.645. CONCLUSIONS: DC of heart rate is a strong and independent predictor of 1-year mortality in patients with severe AS undergoing TAVI.

Autonomic nervous system activity as risk predictor in the medical emergency department: a prospective cohort study.

OBJECTIVES: To evaluate heart rate deceleration capacity, an electrocardiogram-based marker of autonomic nervous system activity, as risk predictor in a medical emergency department and to test its incremental predictive value to the modified early warning score. DESIGN: Prospective cohort study. SETTING: Medical emergency department of a large university hospital. PATIENTS: Five thousand seven hundred thirty consecutive patients of either sex in sinus rhythm, who were admitted to the medical emergency department of the University of Tübingen, Germany, between November 2010 and March 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deceleration capacity of heart rate was calculated within the first minutes after emergency department admission. The modified early warning score was assessed from respiratory rate, heart rate, systolic blood pressure, body temperature, and level of consciousness as previously described. Primary endpoint was intrahospital mortality; secondary endpoints included transfer to the ICU as well as 30-day and 180-day mortality. One hundred forty-two patients (2.5%) reached the primary endpoint. Deceleration capacity was highly significantly lower in nonsurvivors than survivors (2.9 ± 2.1 ms vs 5.6 ± 2.9 ms; p < 0.001) and yielded an area under the receiver-operator characteristic curve of 0.780 (95% CI, 0.745-0.813). The modified early warning score model yielded an area under the receiver-operator characteristic curve of 0.706 (0.667-0.750). Implementing deceleration capacity into the modified early warning score model led to a highly significant increase of the area under the receiver-operator characteristic curve to 0.804 (0.770-0.835; p < 0.001 for difference). Deceleration capacity was also a highly significant predictor of 30-day and 180-day mortality as well as transfer to the ICU. CONCLUSIONS: Deceleration capacity is a strong and independent predictor of short-term mortality among patients admitted to a medical emergency department.