Vitamin K supplementation and arterial calcification in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial.

BACKGROUND: Arterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients. METHODS: In a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized to vitamin K [menaquinone-7 (MK-7), 360 µg daily] or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aortic calcification (AAC) were used to assess arterial calcification. RESULTS: Thirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40% lower after vitamin K supplementation compared with placebo {mean dp-ucMGP difference: -1380 pmol/L [95% confidence interval (CI) -2029 to -730]}. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95% CI -0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95% CI -554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences. CONCLUSIONS: Vitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients.

Two-dimensional global longitudinal strain is superior to left ventricular ejection fraction in prediction of outcome in patients with left-sided infective endocarditis.

BACKGROUND: Impaired cardiac function is the main predictor of poor outcome in infective endocarditis (IE). Global longitudinal strain (GLS) derived from two-dimensional strain echocardiography has proven superior in prediction of long-term outcome as compared to left ventricular ejection fraction (LVEF) in valvular disease and heart failure in general. Whether measurements of cardiac deformation can predict survival in patients with IE has not previously been investigated. METHODS: The study included consecutive patients with Duke definite IE who underwent transthoracic and transesophageal echocardiography within 7 days. Clinical and echocardiographic markers associated with 1-year survival were identified using a Cox-proportional hazards model that included propensity adjustment for surgery. Reclassification statistics including receiver operating characteristic curves and net reclassification improvement were applied to LVEF and GLS, respectively. RESULTS: A cohort of 190 patients met eligibility criteria. LVEF and GLS were both prognostic markers of mortality. Independent markers of 1-year mortality were S. aureus IE (HR:2.02; 95%CI 1.11-5.72, p = .022), diabetes (HR:2.05; 95%CI 1.12-3.75, p = .020), embolic stroke (HR:3.95; 95%CI 1.93-8.10, p < .001) and LVEF<45% (HR: 3.02; 95% CI 1.70-5.38, p < .001), GLS> -15.4% (HR:2.95; 95%CI 1.52-5.72, p < .001). Adding LVEF<45% to a model with known risk factors of IE did not significantly improve risk classification, whereas addition of GLS to the model resulted in significant increase (AUC = 0.763, p < .001). CONCLUSIONS: When treatment was taken into account, LVEF<45% and GLS > -15.4% were both associated with adverse long-term outcome in left-sided IE. GLS >-15.4 % was significantly associated with 1-year mortality in the multivariate analysis. Further, GLS was superior to LVEF in risk prediction and risk discrimination of long-term outcome in patients with left-sided IE.

[Extravasation of contrast following coronary angiography can be misinterpretated as subarachnoid haemorrhage]. / Ekstravasation af kontrast efter koronarangiografi kan forveksles med subaraknoidalblødning på CT.

Brain parenchymal extravasation of contrast has been described after infusion of larger amounts of iodinated X-ray contrast agent. We describe a case in which a patient after infusion of 500 ml iomeprole 350 mg/ml developed neurological symptoms and a subsequent cerebral computed tomography (CT) scan was interpreted as subarachnoid haemorrhage. The patient was fully recovered within 48 hours, and a follow-up CT scan 26 hours later showed no signs of haemorrhage. In patients with sudden onset of neurological symptoms after infusion of large quantities of contrast media and a CT scan showing signs of subarachnoid haemorrhage, spinal puncture or magnetic resonance imaging should be considered prior to interventional procedures in order to verify the diagnosis.

Once versus twice daily gentamicin dosing for infective endocarditis: a randomized clinical trial.

OBJECTIVES: The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). METHODS: Seventy-one IE patients needing gentamicin treatment according to guidelines were randomized to either once (n = 37) or twice daily (n = 34) doses of gentamicin. Kidney function (glomerular filtration rate, GFR) was measured with an isotope method ((51)Cr-EDTA) at the beginning of treatment and at discharge. Treatment efficacy was assessed by C-reactive protein (CRP) time to half-life, mean CRP and leukocytes. RESULTS: Baseline GFR was similar in the two groups. Both groups displayed a significant fall in GFR from admission to discharge. The mean decrease in GFR was as follows: with once daily gentamicin, 17.0% (95% confidence interval 7.5-26.5), and with twice daily gentamicin, 20.4% (95% confidence interval 12.0-28.8). However, there was no significant difference in the GFR decrease between the once and twice daily regimens (p = 0.573). No difference in infection parameters was demonstrated between the two dosing regimens. CONCLUSIONS: A twice daily gentamicin dosing regimen is neither less nephrotoxic nor more efficient than a once daily regimen in the treatment of IE patients. When indicated, gentamicin may therefore also be administered as a single-dose regimen in the treatment of IE patients.

Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome.

INTRODUCTION: The Brugada Syndrome (BrS), an inherited syndrome associated with a high incidence of sudden cardiac arrest, has been linked to mutations in four different genes leading to a loss of function in sodium and calcium channel activity. Although the transient outward current (I(to)) is thought to play a prominent role in the expression of the syndrome, mutations in I(to)-related genes have not been identified as yet. METHODS AND RESULTS: One hundred and five probands with BrS were screened for ion channel gene mutations using single strand conformation polymorphism (SSCP) electrophoresis and direct sequencing. A missense mutation (R99H) in KCNE3 (MiRP2) was detected in one proband. The R99H mutation was found 4/4 phenotype positive and 0/3 phenotype-negative family members. Chinese hamster ovary (CHO)-K1 cells were co-transfected using wild-type (WT) or mutant KCNE3 and either WT KCND3 or KCNQ1. Whole-cell patch clamp studies were performed after 48 hours. Interactions between Kv4.3 and KCNE3 were analyzed in co-immunoprecipitation experiments in human atrial samples. Co-transfection of R99H-KCNE3 with KCNQ1 produced no alteration in current magnitude or kinetics. However, co-transfection of R99H KCNE3 with KCND3 resulted in a significant increase in the I(to) intensity compared to WT KCNE3+KCND3. Using tissues isolated from left atrial appendages of human hearts, we also demonstrate that K(v)4.3 and KCNE3 can be co-immunoprecipitated. CONCLUSIONS: These results provide definitive evidence for a functional role of KCNE3 in the modulation of I(to) in the human heart and suggest that mutations in KCNE3 can underlie the development of BrS.

The ischemic electrocardiogram: a harbinger for ischemic heart disease independent of the blood pressure level. The Copenhagen City Heart Study.

Information is limited on the co-existence and prognostic association of the ischemic electrocardiogram (ECG) and blood pressure. Prospectively collected data sets from 28,118 examinations in the Copenhagen City Heart Study were analyzed for cardiac morbidity and mortality for a 5.9-year follow-up. The prognosis of the ECG, independently of blood pressure, was examined. The Cox proportional hazard model was employed to evaluate the prognostic implications of ECG findings and relative risk was adjusted for age and multivariately adjusted for traditional cardiovascular risk factors. End-points were (1) fatal and non-fatal ischemic heart disease (IHD) events and (2) cardiovascular disease (CVD) mortality. During a total follow-up period of 166,471 person years (mean: 5.9 years) 1.481 IHD events were recorded and 1.051 CVD deaths. The relative risk of an ischemic ECG was independent of the blood pressure level. The multivariately adjusted relative risk for fatal and non-fatal IHD for the ischemic ECG was 1.70 (95% CI: 1.39-2.09, p < 0.001) in women, and 1.96 (95% CI: 1.67-2.30, p < 0.001) in men, and for CVD mortality 1.71 (95% CI: 1.34-2.17, p < 0.001) in women and 2.08 (95% CI: 1.74-2.49, p < 0.001) in men. An ECG with left ventricular hypertrophy (LVH) and ST-depression was the finding with the highest risk for future events. LVH by ECG voltage-only was associated with no statistically increased risk, except for men treated for arterial hypertension.