vitamin-k-semiquinone-radical and Death--Sudden--Cardiac

 The ABC (age, biomarkers, and clinical history)-stroke and ABC-bleeding are biomarker-based scores proposed to predict stroke and bleeding, but non-specificity of biomarkers is common, predicting different clinical events at the same time. We assessed the predictive performance of the ABC-stroke and ABC-bleeding scores, for outcomes beyond ischemic stroke and major bleeding, in a cohort of atrial fibrillation (AF) patients..  We included AF patients stable on vitamin K antagonists for 6 months. The ABC-stroke and ABC-bleeding were calculated and the predictive values for myocardial infarction (MI), acute heart failure (HF), a composite of cardiovascular events, and all-cause deaths were compared..  We included 1,044 patients (49.2% male; median age 76 [71-81] years). During 6.5 (4.3-7.9) years, there were 58 (5.6%) MIs, 98 (9.4%) acute HFs, 167 (16%) cardiovascular events, and 418 (40%) all-cause deaths. There were no differences in mean ABC-stroke and ABC-bleeding scores in patients with/without MI (.  In AF patients, the ABC-stroke and ABC-bleeding scores demonstrated similar predictive ability for outcomes beyond stroke and bleeding, including MI, acute HF, a composite of cardiovascular events, and all-cause deaths. This is consistent with nonspecificity of biomarkers that predict "sick" patients or poor prognosis overall.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Atrial Fibrillation; Biomarkers; Cardiovascular Agents; Cause of Death; Comorbidity; Death, Sudden, Cardiac; Decision Support Techniques; Female; Heart Failure; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Prognosis; ROC Curve; Severity of Illness Index; Stroke; Vitamin K

Atrial fibrillation, the most frequent arrhythmia, has a growing incidence with increasing age and the most important complication of the disease is thromboembolic events that may be prevented by antivitamin K. They are the most efficient therapeutic class for the prevention of these events but they are associated with an increased haemorrhagic risk leading to a reduced prescription in general practice. Optimisation of the management should be based on an individual evaluation of the thromboembolic and haemorrhagic risks, taking into account age, the presence of an associated heart disease, hypertension, diabetes, history of cerebrovascular event, history of previous haemorrhagic event and the ability to achieve a stable target INR. The challenge in ventricular arrhythmias lies in identifying a high risk of sudden death, mainly related to ventricular fibrillation. In patients with structural heart disease, left ventricular dysfunction is the strongest predictor of sudden death. Non invasive markers such as non sustained ventricular tachycardia, late ventricular potentials, decreased heart rate variability and baroreflex sensitivity, and repolarization altemans are further elements to assess risk. However, most of these markers have a poor positive predictive value and a low specificity. In patients with normal hearts, genetic predisposition may in the future identify high risk patients. The electrophysiologic study with programmed ventricular stimulation remains a costly and invasive method and only has a strong positive predictive value in ischemic cardiomyopathy. More precise algorithms for risk stratification are thus needed that may help the strategy of therapy with prophylactic implantable cardioverter defibrillator in the future.

Topics: 4-Hydroxycoumarins; Age Factors; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Baroreflex; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Diabetes Complications; Electrocardiography; Heart Diseases; Heart Rate; Hemorrhage; Humans; Hypertension; Indenes; International Normalized Ratio; Myocardial Ischemia; Risk Assessment; Risk Factors; Stroke; Tachycardia, Ventricular; Thromboembolism; Ventricular Dysfunction, Left; Ventricular Fibrillation; Vitamin K

Cardiovascular collapses, syncopes, and sudden deaths have been observed following the rapid administration of intravenous vitamin K. Our objectives were to characterize the effects of vitamin K on cardiac action potentials and to evaluate effects of vitamin K on sodium and potassium currents, namely I(Na), I(Kr), and I(Ks).. Guinea pig hearts (n = 21) were paced at a cycle length of 250 msec and exposed to vitamin K at 1.15-4.6 micromol/L (2.5-10 mg/L). Monophasic action potential duration measured at 90% repolarization (MAPD(90)) was not significantly reduced (-1.6 +/- 0.3 msec; P >.05; N.S.) at 1.15 micromol/L, but increased by 6.5 +/- 0.4 msec (P <.05) at 2.3 micromol/L. MAPD(90) was not measurable at 4.6 micromol/L, as a result of inexcitability. Patch-clamp experiments in ventricular myocytes demonstrated a approximately 50% reduction in I(Na) by 10 micromol/L vitamin K and a concentration-dependent reduction of the K(+) current elicited by short depolarizations (250 msec; I(K250)). Estimated IC(50) for I(K250), mostly representing I(Kr), was 2.3 micromol/L. Vitamin K was less potent to block the K(+) current elicited by long depolarizations (5,000 msec; I(K5000)), mostly representing I(Ks), with an estimated IC(50) over 100 micromol/L.. Therapeutic concentrations ( approximately 1.5 micromol/L) of intravenous vitamin K modulate cardiac action potential by blocking ionic currents involved in cardiac depolarization and repolarization.

Topics: Action Potentials; Animals; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Guinea Pigs; Heart; Infusions, Intravenous; Potassium Channels; Sodium Channels; Syncope; Vitamin K