Imbalance between plasma double-stranded DNA and deoxyribonuclease activity predicts mortality after out-of-hospital cardiac arrest.

AIM: Despite an increased rate of return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) patients, almost half of patients do not survive up to hospital discharge. Understanding pathophysiological mechanisms of post-cardiac arrest syndrome is essential for developing novel therapeutic strategies. During systemic inflammatory responses and concomitant cell death, double-stranded (ds) DNA is released into circulation, exerting pro-inflammatory effects. Deoxyribonuclease (DNase) degrades dsDNA. The role of DNase activity in OHCA survivors and impact on clinical outcome has not been analyzed yet. METHODS: In a prospective, single-center study, dsDNA and DNase activity were determined at hospital admission (acute phase) and 24 h (subacute phase) after ROSC. The ratio between dsDNA levels and DNase activity was calculated to determine the extent of dsDNA release in relation to the patients' capacity of degradation. Thirty-day mortality was defined as study end point. RESULTS: We enrolled 64 OHCA survivors, of whom 26.6% (n = 17) died within 30 days. A peak of circulating dsDNA was observed at admission which decreased within 24 h. DNase activity did not differ between acute and subacute phase, while dsDNA load per DNase activity significantly decreased. The ratio between dsDNA levels and DNase activity in the subacute phase was the strongest predictor of 30-day mortality with an adjusted HR per 1 SD of 3.59 (95% CI, 1.80-7.18, p < 0.001). CONCLUSION: Disproportionally increased dsDNA levels uncompensated by DNase activity are a strong predictor of mortality in OHCA survivors. This pilot study points to a potentially protective effect of DNase activity in patients undergoing cardiac arrest.

Assessment of left ventricular ejection fraction with late-systolic and mid-diastolic cardiac phases using multi-slice computed tomography.

INTRODUCTION: Multi-slice computed tomography (MSCT) is an accurate tool for the assessment of left ventricular ejection fraction (LVEF). However, in order to reduce radiation dose, prospective acquisition protocols are currently used, in which the end-systole and end-diastole are not scanned. Our aim was to study the accuracy of the assessment of LVEF using fixed late-systolic and mid-diastolic cardiac phases compared with echocardiography. METHODS: MSCT-derived LVEF was measured with off-line commercially available software packages, and compared with echocardiography-derived LVEF using the Simpson's method. LVEF was categorized as normal vs. abnormal (50% cut-off) and was also analyzed as a quantitative parameter. Bland-Altman plots and Pearson correlations were used for inter-technique comparisons. RESULTS: 58 patients were included. The sensitivity and specificity of fixed-phase MSCT when compared with echocardiography for detection of LVEF ≤50% was 79% (95% CI = 65-89%) and 43% (10-82%). Misclassification was associated with older age (68 ± 12 vs. 54 ± 13 years, p < 0.01), faster heart rate (79 ± 14 vs. 68 ± 10 bpm, p = 0.01), and LV hypertrophy (86% vs. 52%, p = 0.03). The quantitative comparison revealed no correlation (r = 0.095, p = 0.478) and a significantly different LVEF (median[IQR], 57.0[50.5-63.1]% vs. 61.0[57.3-64.3]%, p = 0.03). The observed bias between the two methods was -3.7% with broad limits of agreement (±25.5%). CONCLUSIONS: Fixed-phase MSCT assessment using late-systole and mid-diastole agreed in defining normal and abnormal LVEF in 76% of patients when compared with echocardiography. Quantitation of LVEF by this method yielded significantly lower values of LVEF and showed no correlation. Thus, accurate quantitation of LVEF by MSCT requires the acquisition of end-systolic and end-diastolic phases.

Beneficial effects of levosimendan on survival in patients undergoing extracorporeal membrane oxygenation after cardiovascular surgery.

BACKGROUND: The impact of levosimendan treatment on clinical outcome in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery is unknown. We hypothesized that the beneficial effects of levosimendan might improve survival when adequate end-organ perfusion is ensured by concomitant ECMO therapy. We therefore studied the impact of levosimendan treatment on survival and failure of ECMO weaning in patients after cardiovascular surgery. METHODS: We enrolled a total of 240 patients undergoing veno-arterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care centre into our observational single-centre registry. RESULTS: During a median follow-up period of 37 months (interquartile range 19-67 months), 65% of patients died. Seventy-five per cent of patients received levosimendan treatment within the first 24 h after initiation of ECMO therapy. Cox regression analysis showed an association between levosimendan treatment and successful ECMO weaning [adjusted hazard ratio (HR) 0.41; 95% confience interval (CI) 0.22-0.80; P=0.008], 30 day mortality (adjusted HR 0.52; 95% CI 0.30-0.89; P=0.016), and long-term mortality (adjusted HR 0.64; 95% CI 0.42-0.98; P=0.04). CONCLUSIONS: These data suggest an association between levosimendan treatment and improved short- and long-term survival in patients undergoing ECMO support after cardiovascular surgery.

Hepatosplenic Abscesses and Osteomyelitis of the Spine in an Immunocompetent Adult with Cat Scratch Disease.

We present an 18-year-old, immunocompetent Austrian military conscript with cervical lymphadenopathy, fever, back-pain, and persistent inflammation markers despite two weeks of antimicrobial therapy with ampicillin/sulbactam. All specific laboratory investigations for identification of a specific etiology, including blood cultures and autoantibodies, were inconspicuous. Abdominal computed tomography showed multiple hypodense hepatosplenic lesions and osteomyelitis of the thoracic and lumbar spine with base plate fracture. Based on the patient's history, clinical presentation, and radiological findings, serology for cat scratch disease (CSD) was performed and high B. henselae specific IgM and IgG antibodies were detected. Due to its variety of clinical presentations, diagnosis of CSD is challenging, especially in the absence of a history of specific exposure. This case report shall remind the physician that cat scratch disease is a common disease, mainly presenting with fever and lymphadenopathy in young patients. Nevertheless CSD has many different and rare forms of presentations, including hepatosplenic lesions and bone involvement as shown in this case.

Evolving biomarkers improve prediction of long-term mortality in patients with stable coronary artery disease: the BIO-VILCAD score.

OBJECTIVE: Algorithms to predict the future long-term risk of patients with stable coronary artery disease (CAD) are rare. The VIenna and Ludwigshafen CAD (VILCAD) risk score was one of the first scores specifically tailored for this clinically important patient population. The aim of this study was to refine risk prediction in stable CAD creating a new prediction model encompassing various pathophysiological pathways. Therefore, we assessed the predictive power of 135 novel biomarkers for long-term mortality in patients with stable CAD. DESIGN, SETTING AND SUBJECTS: We included 1275 patients with stable CAD from the LUdwigshafen RIsk and Cardiovascular health study with a median follow-up of 9.8 years to investigate whether the predictive power of the VILCAD score could be improved by the addition of novel biomarkers. Additional biomarkers were selected in a bootstrapping procedure based on Cox regression to determine the most informative predictors of mortality. RESULTS: The final multivariable model encompassed nine clinical and biochemical markers: age, sex, left ventricular ejection fraction (LVEF), heart rate, N-terminal pro-brain natriuretic peptide, cystatin C, renin, 25OH-vitamin D3 and haemoglobin A1c. The extended VILCAD biomarker score achieved a significantly improved C-statistic (0.78 vs. 0.73; P = 0.035) and net reclassification index (14.9%; P < 0.001) compared to the original VILCAD score. Omitting LVEF, which might not be readily measureable in clinical practice, slightly reduced the accuracy of the new BIO-VILCAD score but still significantly improved risk classification (net reclassification improvement 12.5%; P < 0.001). CONCLUSION: The VILCAD biomarker score based on routine parameters complemented by novel biomarkers outperforms previous risk algorithms and allows more accurate classification of patients with stable CAD, enabling physicians to choose more personalized treatment regimens for their patients.

C-reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C-reactive protein (CRP) in patients with HFpEF. METHODS AND RESULTS: Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high-sensitivity assay. During a median follow-up of 9.7 years 40% of these patients died. CRP predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.20 [95% confidence interval (CI) 1.02-1.40, P = 0.018] and cardiovascular mortality with a HR of 1.32 (95% CI 1.08-1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N-terminal pro B-type natriuretic peptide (Nt-proBNP): the lowest 5-year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt-proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt-proBNP and CRP with a 5-year rate of 36.5%. CONCLUSION: It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.

Echo Doppler parameters predict response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to reduce heart failure related morbidity and mortality. However, approximately 30% of patients do not respond to CRT. We investigated the usefulness of Echo Doppler parameters to predict reverse remodelling, functional improvement and mortality following CRT. MATERIALS AND METHODS: Our population consists of 200 consecutive heart failure patients evaluated for ventricular dyssynchrony by echocardiography between February 1999 and May 2007 who subsequently received CRT. Patients were reassessed for signs of reverse remodelling after a mean follow-up of 10 months. Information on vital status was obtained from local registration authorities. RESULTS: Three parameters significantly predicted reverse remodelling in the logistic regression analysis: the Q-to-E-wave-delay (QED) at a cutoff of 550 ms (odds ratio 4.5, P-value 0.001), the interventricular mechanical delay (IVMD) at a cutoff of 60 ms (odds ratio 2.4, P-value 0.02), and the aortic electromechanical delay (A-EMD) at a cutoff of 140 ms (odds ratio 2.9, P-value 0.004). Furthermore, the QED and the IVMD also predicted all-cause mortality (hazard ratio 0.36, P-value 0.02 and 0.21, P-value 0.004, respectively). Adjustment for confounders did not alter the results. CONCLUSIONS: The QED and IVMD predict reverse remodelling and survival following CRT. These parameters are easy to obtain, provide valuable prognostic information, and should thus be measured in CRT candidates evaluated by echocardiography.