vitamin-k-semiquinone-radical and Heart-Failure

The prevalence of atrial fibrillation (AF) is increasing as the population ages. AF treatment-related complications also increase markedly in older adults (defined as ≥75 years of age for this review). The older AF population has a high risk of stroke, bleeding, and death. Syncope and fall-related injuries are the most common reasons for nonprescription of oral anticoagulation (OAC), and are more common in older adults when OACs are used with antiarrhythmic drugs. Digoxin may be useful for rate control, but associations with increased mortality limit its use. Beyond rate and rhythm control considerations, stroke prophylaxis is critical to AF management, and the benefits of direct OACs, compared with warfarin, extend to older adults. Invasive procedures such as AF catheter ablation, pacemaker implantation/atrioventricular junction ablation, and left atrial appendage occlusion may be useful in appropriately selected cases. However, older adults have generally been under-represented in clinical trials.

Topics: Accidental Falls; Aged; Alcohol Drinking; Anti-Arrhythmia Agents; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Cognitive Dysfunction; Coronary Artery Disease; Cost-Benefit Analysis; Decision Making, Shared; Dementia; Diabetes Mellitus; Dual Anti-Platelet Therapy; Exercise; Frailty; Heart Failure; Humans; Hypertension; Overweight; Polypharmacy; Primary Prevention; Risk Assessment; Secondary Prevention; Sleep Apnea, Obstructive; Stroke; Vitamin K; Weight Loss

Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

Topics: Anticoagulants; Antidotes; Coronary Artery Disease; Drug Discovery; Factor XI; Factor XII; Heart Failure; Heparin; Humans; Peripheral Arterial Disease; Stroke; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs.. We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione.. Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs.. In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Cardiovascular Diseases; Diarrhea; Fibrinolytic Agents; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Obesity; Phenindione; Phenprocoumon; Vitamin K; Warfarin

Many patients with atrial fibrillation have substantial symptoms despite ventricular rate control and require restoration of sinus rhythm to improve their quality of life. Acute restoration (ie, cardioversion) and maintenance of sinus rhythm in patients with atrial fibrillation are referred to as rhythm control. The decision to pursue rhythm control is based on symptoms, the type of atrial fibrillation (paroxysmal, persistent, or long-standing persistent), patient comorbidities, general health status, and anticoagulation status. Many patients have recurrent atrial fibrillation and require further intervention to maintain long term sinus rhythm. Antiarrhythmic drug therapy is generally recommended as a first-line therapy and drug selection is on the basis of the presence or absence of structural heart disease or heart failure, electrocardiographical variables, renal function, and other comorbidities. In patients who continue to have recurrent atrial fibrillation despite medical therapy, catheter ablation has been shown to substantially reduce recurrent atrial fibrillation, decrease symptoms, and improve quality of life, although recurrence is common despite continued advancement in ablation techniques.

Topics: Administration, Oral; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Electric Countershock; Heart Failure; Heart Rate; Humans; Practice Guidelines as Topic; Quality of Life; Stroke; Thromboembolism; Time Factors; Vitamin K

Thromboembolism contributes to morbidity and mortality in patients with heart failure (HF), and atrial fibrillation (AF) is one of the main factors promoting this complication. As they share many risk factors, HF and AF frequently coexist, and patients with both conditions are at a particularly high risk of thromboembolism. Non-vitamin K antagonist oral anticoagulants (NOACs) are direct antagonists of thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban and edoxaban), and were designed to overcome the limitations of vitamin K antagonists. Compared with warfarin in non-valvular AF, NOACs demonstrated non-inferiority with better safety, most particularly for intracranial haemorrhages. Therefore, the European Society of Cardiology guidelines recommend NOACs for most patients with non-valvular AF. Subgroups of patients with both AF and HF from the pivotal studies investigating the safety and efficacy of NOACs have been analysed and, for each NOAC, results were similar to those of the total analysis population. A recent meta-analysis of these subgroups has confirmed the better efficacy and safety of NOACs in patients with AF and HF - particularly the 41% decrease in the incidence of intracranial haemorrhages. The prothrombotic state associated with HF suggests that patients with HF in sinus rhythm could also benefit from treatment with NOACs. However, in the absence of clinical trial data supporting this indication, current guidelines do not recommend anticoagulant treatment of patients with HF in sinus rhythm. In conclusion, recent analyses of pivotal studies support the use of NOACs in accordance with their indications in HF patients with non-valvular AF.

Topics: Administration, Oral; Anticoagulants; Heart Failure; Humans; Thromboembolism; Vitamin K

Oral vitamin K antagonists are highly efficacious in the prevention and treatment of thromboembolic disease. Optimal use of these agents in clinical practice is challenged by their narrow therapeutic window. The proportion of time spent in the International Normalized Ratio (INR) range of 2.0-3.0 [time in the therapeutic range (TTR)] has been closely associated with adverse outcomes, i.e., stroke, hemorrhage, mortality. Although TTR is a validated marker, it has several limitations. TTR does not capture short-term risks associated with highly variable periods or periods characterized by extreme deviations in INR. Because TTR measurement is limited to consecutive periods of warfarin exposure, it does not inform the risks associated with gap periods of 56 days or greater as these time intervals are excluded from end-point rate calculations. Because individuals with gaps in monitoring represent a different patient population than those without gaps, e.g., less adherent, more acutely ill, more frequent transitions in health status, TTR analyses are likely most valid and informative for individuals with uninterrupted monitoring of the INR. Duration of warfarin therapy and patient-specific factors have also been shown to influence TTR. Younger age, female sex, lower income, black race, frequent hospitalizations, polypharmacy, active cancer, decompensated heart failure, substance abuse, psychiatric disorders, dementia, and chronic liver disease have all been associated with lower TTR. Targeted strategies to improve TTR are urgently needed.

Topics: Age Factors; Anticoagulants; Chronic Disease; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Liver Diseases; Male; Neoplasms; Sex Factors; Stroke; Substance-Related Disorders; Thromboembolism; Vitamin K; Warfarin

Arial fibrillation (AF) is the most commonly occurring sustained arrhythmia in the United States and is associated with increased mortality. AF is a risk factor for ischemic stroke, and risk factors for AF include comorbid conditions such as congestive heart failure, diabetes mellitus, older age, hypertension, diabetes, pulmonary disease, and history of stroke, transient ischemic attack, or heart failure. Risk stratification for ischemic stroke in AF patients is based on scoring a group of risk factors that allows for the appropriate tailoring of antithrombotic therapy. The vitamin K antagonists are effective at reducing ischemic stroke rates in medium-risk to high-risk patients and are therefore generally recommended for this group. However, a large proportion of these patients are not treated with vitamin K antagonists because of the potential for adverse outcomes, particularly in elderly patients. New direct thrombin inhibitors and direct Factor Xa inhibitors in development offer the possibility of simplifying treatment and management although offering similar or better efficacy and safety profiles to warfarin. In light of these potential new treatments, the importance and improvement of risk stratification methods and the resulting recommendations in thromboprophylaxis become even more paramount as they make it more likely that medium-risk to high-risk patients can be treated safely.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Chemoprevention; Comorbidity; Diabetes Mellitus; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Failure; Humans; Risk Factors; Stroke; Vitamin K

Circulating uncarboxylated matrix Gla protein (ucMGP) is possibly related to coronary arterial calcification (CAC) in cardiovascular disease (CVD) patients.. We aimed to evaluate the relationships between circulating ucMGP, CVD pathology and CAC and its interplay with CVD risk factors.. ucMGP was measured in 99 CVD-patients. CAC score was determined by multislice computed tomography. Circulating ucMGP, uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) were assayed by ELISA kits. Vitamin-K status was evaluated by ucOC/cOC ratio.. A tendency for decreased ucMGP was observed for CAC. Circulating ucMGP may reflect certain stages of CVD and CAC. Future studies are needed to clarify its role as potential biomarker.

Topics: Anticoagulants; Atrial Fibrillation; Biomarkers; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Heart Failure; Humans; Matrix Gla Protein; Osteocalcin; Stroke Volume; Vitamin K; Vitamins

Vitamin K is associated with reduced cardiovascular disease risk such as heart failure, possibly by carboxylation of matrix-gla protein (MGP), a potent inhibitor of vascular calcification. The relationship of vitamin K intake or status with cardiac structure and function is largely unknown. Therefore this study aims to investigate the prospective association of vitamin K status and intake with echocardiographic measures.. This study included 427 participants from the Hoorn Study, a population-based cohort. Vitamin K status was assessed at baseline by plasma desphospho-uncarboxylated MGP (dp-ucMGP) with higher concentrations reflecting lower vitamin K status. Vitamin K intake was assessed at baseline with a validated food-frequency questionnaire. Echocardiography was performed at baseline and after a mean follow-up time of 7.6, SD=±0.7 years. We used linear regression for the association of vitamin K status and intake with left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI), adjusted for potential confounders.. The mean age was 66.8, SD=±6.1 years (51% were male). A high vitamin K status was prospectively associated with decreased LVMI (change from baseline to follow-up: -5.0, 95% CI: -10.5;0.4 g/m. This study showed a high vitamin K status being associated with decreased LVMI only in women, while intakes of vitamin K were not associated with any cardiac structure or function measures. These results extend previous findings for a role of vitamin K status to decrease heart failure risk.

Topics: Aged; Cohort Studies; Female; Heart Failure; Humans; Male; Stroke Volume; Ventricular Function, Left; Vitamin K

Congestive heart failure patients have hepatic congestion and abnormal coagulation profiles, increasing perioperative bleeding at time of ventricular assist device implantation. This study examined the impact of the preoperative administration of vitamin K on perioperative blood transfusion requirements.. Retrospectively, 190 patients met inclusion criteria. Patients received no vitamin K (n = 62) or two 10-mg doses of intravenous vitamin K (n = 128) in the 24 hours before assist device implantation. Primary end points included transfusion requirements and reexploration rates for bleeding. Secondary outcomes were pump thrombosis and in-hospital mortality.. Baseline characteristics were similar between the 2 groups, with slight differences (not statistically significant) noted in the Interagency Registry for Mechanically Assisted Circulatory Support profile and total bilirubin levels. The only significant difference noted was the year of implantation (P < .001). Blood product usage was significantly lower in the vitamin K group compared to the no vitamin K group (P < .001). Higher rates of reexploration for bleeding (29.7% vs 13.6%, P = .023) and death at hospital discharge (16.2% vs 2.8%, P = .004) were noted for the no vitamin K group compared with the vitamin K group. After adjusting for age, sex, race, body mass index, Interagency Registry for Mechanically Assisted Circulatory Support profile, total bilirubin, surgeon, and year of operation, reexploration rates and death did not achieve statistical significance. No statistically significant difference was observed in stroke and pump thrombosis rates between the 2 groups.. Preoperative vitamin K administration may help reduce blood product use without any increased risk for strokes or pump thrombosis.

Topics: Antifibrinolytic Agents; Blood Transfusion; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Failure; Heart-Assist Devices; Humans; Incidence; Infusions, Intravenous; Male; Middle Aged; Postoperative Hemorrhage; Preoperative Care; Registries; Retrospective Studies; Survival Rate; Time Factors; United States; Ventricular Function, Left; Vitamin K

Topics: Blood Transfusion; Heart Failure; Heart-Assist Devices; Humans; Vitamin K

The efficacy of direct oral anticoagulants (DOACs) in the management of left ventricular (LV) thrombi remains to be determined, especially in patients with ischemic cardiomyopathy. This retrospective study sought to compare the efficacy of vitamin K antagonists (VKAs) and DOACs in patients with LV thrombi and evaluate the rate of LV thrombus resolution after adjusting anticoagulation.. This observational retrospective study included patients admitted to our institution for LV thrombus between January 2010 and August 2019. The rate of LV thrombus resolution was compared between VKAs and DOACs. Patients without thrombus resolution with DOAC treatment were switched to VKA agents in order to obtain an international normalized ratio (INR) of 3-4.. Between January 2010 and August 2019, 59 consecutive patients with LV thrombi detected by transthoracic echocardiography were included in the study. The mean age was 62 ± 14 years and 16.9% were women. The circumstances of LV thrombus discovery were as follows: acute myocardial infarction or ischemic myocardiopathy (n = 22), stroke (n = 6), chest pain (n = 7), heart failure (n = 11), transthoracic echocardiographic evaluation (n = 11), and ventricular arrhythmias (n = 2). The proportion of patients on DOACs was 28.8% (n = 17), while that of those on VKAs was 71.2% (n = 42). Thrombus resolution was obtained in 70.6% (12/17) of patients on DOACs and in 71.4% (30/42) of those on VKAs (p = 0.9). Patients who failed to respond to DOAC treatment were treated with VKAs, and following this treatment adjustment all LV thrombi were dissolved in the DOAC group (5/5). Five embolic events (8.4% of stroke) occurred before the treatment initiation and six with anticoagulants (2/17 with DOACs [11.8%] and 4/42 with VKAs [9.5%]; p = 0.8).. This retrospective observational study found a similar efficacy between DOAC and VKA agents in patients with LV thrombi (70.6% vs. 71.5%); however, when the thrombus remains, VKAs are still the standard of care as it is possible to control INR levels (3-4) with them.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Arrhythmias, Cardiac; Female; Fibrinolytic Agents; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Stroke; Thrombosis; Vitamin K

 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

Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up.. In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, restricted mean survival time differences were used to evaluate the association among INR categories and the risk of all-cause mortality.. During a median [interquartile range] follow-up of 2.15 years [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients with subtherapeutic and supratherapeutic INR showed higher risks of all-cause mortality, as evidenced by their restricted mean survival time differences at 5 years' follow-up: -0.50; 95%CI, -0.77 to -0.23 years; P < .001; and -0.40; 95%CI, -0.70 to -0.11 years; P = .007, respectively, compared with INR 2-3.. In acute heart failure patients on treatment with VKA for NVAF, INR values out of normal range at admission were independently associated with a higher long-term mortality risk.

Topics: Acute Disease; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; International Normalized Ratio; Male; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Spain; Survival Rate; Thromboembolism; Time Factors; Vitamin K

Large artery stiffening contributes to the pathophysiology of heart failure (HF) and associated comorbidities. MGP (matrix Gla-protein) is a potent inhibitor of vascular calcification. MGP activation is vitamin K-dependent. We aimed (1) to compare dp-ucMGP (dephospho-uncarboxylated MGP) levels between subjects with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) and subjects without HF; (2) to assess the relationship between dp-ucMGP levels and arterial stiffness; and (3) to assess the relationship between warfarin use, dp-ucMGP levels, and arterial stiffness in HF. We enrolled 348 subjects with HFpEF (n=96), HFrEF (n=53), or no HF (n=199). Carotid-femoral pulse wave velocity, a measure of large artery stiffness, was measured with arterial tonometry. Dp-ucMGP was measured with ELISA. Dp-ucMGP levels were greater in both HFrEF (582 pmol/L; 95% CI, 444-721 pmol/L) and HFpEF (549 pmol/L; 95% CI, 455-643 pmol/L) compared with controls (426 pmol/L; 95% CI, 377-475 pmol/L; ANCOVA P=0.0067). Levels of dp-ucMGP were positively associated with carotid-femoral pulse wave velocity (standardized β, 0.31; 95% CI, 0.19-0.42; P<0.0001), which was also true in analyses restricted to patients with HF (standardized β, 0.34; 95% CI, 0.16-0.52; P=0.0002). Warfarin use was significantly associated with carotid-femoral pulse wave velocity (standardized β, 0.13; 95% CI, 0.004-0.26; P=0.043), but this relationship was eliminated after adjustment for dp-ucMGP. In conclusion, levels of dp-ucMGP are increased in HFpEF and HFrEF and are independently associated with arterial stiffness. Future studies should investigate whether vitamin K supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffness in HFpEF and HFrEF.

Topics: Aged; Calcium-Binding Proteins; Extracellular Matrix Proteins; Female; Heart Failure; Humans; Male; Matrix Gla Protein; Middle Aged; Prospective Studies; Pulse Wave Analysis; Stroke Volume; Vascular Stiffness; Vitamin K; Warfarin

Topics: Anticoagulants; Factor Xa; Heart Failure; Heart-Assist Devices; Humans; International Normalized Ratio; Reproducibility of Results; Vitamin K

Microcirculatory changes contribute to clinical symptoms and disease progression in chronic heart failure (CHF). A depression of coronary flow reserve is associated with a lower myocardial capillary density in biopsies. We hypothesized that changes in cardiac microcirculation might also be reflected by a systemic reduction in capillaries and visualized by sublingual videomicroscopy. The aim was to study in vivo capillary density and glycocalyx dimensions in patients with CHF vs healthy controls.. Fifty patients with ischaemic and nonischaemic CHF and standard treatment were compared to 35 healthy age-matched subjects in a prospective cross-sectional study. Sublingual microcirculation was visualized using a sidestream darkfield videomicroscope. Functional and perfused total capillary densities were compared between patients and controls. A reduced glycocalyx thickness was measured by an increased perfused boundary region (PBR).. Median functional and total perfused capillary densities were 30% and 45% lower in patients with CHF (both P < .001). Intake of oral vitamin K antagonists was associated with significantly lower capillary densities (P < .05), but not independent of NT-proBNP. Dimensions of the glycocalyx were marginally lower in CHF patients than in healthy controls (<7% difference). However, PBR correlated significantly with inflammation markers (fibrinogen: r = .58; C-reactive protein: r = .42), platelet counts (r = .36) and inversely with measures of liver/renal function such as bilirubin (r = -.38) or estimated glomerular filtration rate (r = -.34) in CHF patients.. CHF patients have got a markedly lower functional and total perfused capillary density in sublingual microvasculature when compared to controls, indicating a systemic decrease in microcirculation.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Biomarkers; Capillaries; Chronic Disease; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Glycocalyx; Heart Failure; Humans; Male; Microcirculation; Microscopy, Video; Microvascular Rarefaction; Microvessels; Middle Aged; Mouth Floor; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Count; Prospective Studies; Stroke Volume; Ventricular Dysfunction, Left; Vitamin K

The efficacy and tolerability of vitamin K antagonists (VKAs) depends on the quality of anticoagulant control, reflected by the mean time in therapeutic range (TTR) of international normalized ratio 2.0 to 3.0. In the present study, we aimed to investigate the association between TTR and change in TTR (ΔTTR) with the risk of mortality and clinically significant events in a consecutive cohort of atrial fibrillation (AF) patients.. We included 1361 AF patients stable on VKAs (international normalized ratio 2.0-3.0) during at least the previous 6 months. After 6 months of follow-up we recalculated TTR, calculated ΔTTR (ie, the difference between baseline and 6-month TTRs) and investigated the association of both with the risk of mortality and "clinically significant events" (defined as the composite of stroke or systemic embolism, major bleeding, acute coronary syndrome, acute heart failure, and all-cause deaths).. The median ΔTTR at 6 months of entry was 20% (interquartile range 0-34%), 796 (58.5%) patients had a TTR reduction of at least 20%, while 330 (24.2%) had a TTR <65%. During follow-up, 34 (2.5% [4.16% per year]) patients died and 61 (4.5% [7.47% per year]) had a clinically significant event. Median ΔTTR was significantly higher in patients who died (35.5% vs 20%; P = 0.002) or sustained clinically significant events (28% vs 20%; P = 0.022). Based on Cox regression analyses, the overall risk of mortality at 6 months for each decrease point in TTR was 1.02 (95% CI, 1.01-1.04; P = 0.003), and the risk of clinically significant events was 1.01 (95% CI, 1.00-1.03; P = 0.028). Patients with TTR <65% at 6 months had higher risk of mortality (hazard ratio = 2.96; 95% CI, 1.51-5.81; P = 0.002) and clinically significant events (hazard ratio = 1.71; 95% CI, 1.01-2.88; P = 0.046).. Our findings suggest that in AF patients anticoagulated with VKAs, a change in TTR over 6 months (ie, ΔTTR) is an independent risk factor for mortality and clinically significant events. Even in a cohort with good anticoagulation control, the risk for mortality and clinically significant events increases with every point deterioration of TTR.

Topics: Acenocoumarol; Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Regression Analysis; Risk Factors; Stroke; Vitamin K

Atrial fibrillation (AF) is common in patients with heart failure and is associated with higher mortality. Although previous studies have reported that direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in out-patients with AF, it remains unclear whether DOACs reduce mortality in hospitalized heart failure (HHF) patients with AF. Therefore, we examined the impact of DOACs on mortality in this group of patients.. Consecutive 497 HHF patients with AF were retrospectively registered and divided into three groups on the basis of the presence of anticoagulant therapy: non-anticoagulant group (Non, n = 90), Vit K antagonists (VKAs) group (n = 257) and DOACs group (n = 150). We followed up all the patients for mortality.. In the Kaplan-Meier analysis (mean follow-up of 1093 days), all-cause mortality was significantly lower in the VKAs and DOACs groups than in the Non group (31.1% and 15.3% vs. 43.3%, log-rank P < 0.001). In the multivariable Cox proportional hazard analysis after adjusting for other potential confounding factors, usage of DOACs and VKAs were independently associated with lower mortality in HHF patients AF (DOACs, HR 0.356, P = 0.001; VKAs, HR 0.472, P = 0.002). Furthermore, the propensity-matched 1:1 cohort was assessed based on the propensity score (DOACs, n = 114 and VKAs, n = 114). All-cause mortality was significantly lower in the DOACs group than in the VKAs group in the post-matched cohort (12.3% vs. 35.1%, log-rank P = 0.038). In the Cox proportional hazard analysis, the use of DOACs was associated with lower mortality in the post-matched cohort (HR 0.526, P = 0.041).. Appropriate use of anticoagulants in HHF patients with AF is important, and DOACs potentially improve all-cause mortality in such patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Chi-Square Distribution; Comorbidity; Female; Heart Failure; Hospitalization; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Prevalence; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin K

Anticoagulation control in patients with atrial fibrillation (AF) has a multidisciplinary approach although is usually managed by general practitioners (GP) or haematologists. The aim of our study was to assess the quality of anticoagulation control with vitamin K antagonists (VKAs) in relation to the responsible specialist in a "real-world" AF population.. We consecutively enrolled VKA anticoagulated patients included in the FANTASIIA Registry from 2013 to 2015. We analysed demographical, clinical characteristics and the quality of anticoagulation control according to the specialist responsible (ie GPs or haematologists).. Data on 1584 patients were included (42.5% females, mean age 74.0 ± 9.4 years): 977 (61.7%) patients were controlled by GPs and 607 (38.3%) by haematologists. Patients managed by GPs had higher previous heart disease (53.2% vs 43.3%, P < .001), heart failure (32.9% vs 26.5%, P < .008) and dilated cardiomyopathy (15.2% vs 8.7%, P < .001) with better renal function (69.3 ± 24.7 vs 63.1 ± 21.4 mL/min, P < .001) compared to patients managed by haematologists. There was no difference between groups in the type of AF, CHA. About 60% of AF patients anticoagulated with VKAs had poor anticoagulation control (ie TTR<70%), and their management was only slightly better than when it is managed by general practitioners.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Dilated; Electric Countershock; Female; General Practice; Heart Failure; Hematology; Humans; Kidney; Male; Prospective Studies; Quality of Health Care; Registries; Risk Factors; Vitamin K

A few reports have investigated the association of dietary vitamin intakes with risk of heart failure in Asia. Therefore, we examined the relation between dietary intakes of fat-soluble vitamins A, K, E, and D and mortality from heart failure in the Japanese population.. A total of 23 099 men and 35 597 women ages 40 to 79 y participated in the Japan Collaborative Cohort Study and completed a food frequency questionnaire from which dietary intakes of vitamins A, K, E, and D were calculated. The Cox proportional hazard model was used to estimate the sex-specific risks of heart failure mortality according to increasing quintiles of fat-soluble vitamin intakes.. During the median 19.3 y follow-up period, there were 567 deaths from heart failure (240 men, 327 women). Dietary vitamin A intake showed no association with heart failure mortality in both sexes; however, the reduced risk was observed in women but not in men with dietary intakes of vitamins K, E, and D. The multivariable hazard ratios (95% confidence interval) in the highest versus the lowest intake quintiles among women were 0.63 (0.45-0.87; P for trend = 0.006) for vitamin K, 0.55 (0.36-0.78; P for trend = 0.006) for vitamin E, and 0.66 (0.48-0.93; P for trend = 0.01) for vitamin D. The association for each vitamin was slightly attenuated but remained statistically significant after mutual adjustment for intakes of the other vitamins.. High dietary intakes of fat-soluble vitamins K, E, and D were associated with a reduced risk of heart failure mortality in Japanese women but not men.

Topics: Adult; Aged; Diet; Diet Surveys; Eating; Female; Follow-Up Studies; Heart Failure; Humans; Japan; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Component Transfusion; Breast Neoplasms; Female; Heart Failure; Humans; International Normalized Ratio; Plasma; Pleural Effusion, Malignant; Preoperative Care; Stroke; Thoracentesis; Transfusion Reaction; Vitamin K; Warfarin

To determine the temporal trend in poorly-controlled anticoagulated patients.. A longitudinal study was conducted on a non-unselected sample of all patients seen in a health centre over a period of 3 years (2011-2013). Patients who received anti-vitamin K anticoagulation for at least 6 months due to non-valvular atrial fibrillation were selected, obtaining a final sample of 130 patients.. The mean age of the sample was 77.0±1.5 years and 53.1% were male. The prevalence of hypertension and diabetes mellitus was 90% and 33.8%, respectively, and 11.5% and 14.6% had had heart failure or a stroke, respectively. The mean number of medications taken by patients was 7.6±0.6. The prevalence of insufficient control of time in therapeutic range, calculated by Rosendaal, was 60.2% in 2011, 54.2% in 2010, and 43.4% in 2012. On analysing the time in the therapeutic range in patients with impaired control in the first quarter of follow-up, it was observed to remain low in subsequent years: 69.7% vs 55%, P=.0005, in 2011; 71.9% vs 59.3%, P=.0015 in 2012; and 74.7% vs 60%, P=.0005 in 2013.. Our study shows that patients with inadequate time in therapeutic range have a tendency to stay in poor control, suggesting the need for early clinical decisions in patients on anticoagulants, taking into account the prognosis and economic costs of atrial fibrillation and treatment.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Longitudinal Studies; Male; Primary Health Care; Retrospective Studies; Stroke; Time Factors; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Heart Failure; Humans; Thromboembolism; Vitamin K

Matrix Gla protein (MGP) is a natural inhibitor of tissue calcification. In a previous study, we observed the positive association between abnormal concentrations of uncarboxylated MGP species and increased mortality risk in stable vascular patients. We explore whether co-incidence of abnormal status of uncarboxylated MPG and heart failure (HF) affects the mortality risk.. We examined 799 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total uncarboxylated MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays.. Elevated (>100 ng/L) circulating brain natriuretic peptide (BNP) and abnormal status of plasma uncarboxylated MGP species (i.e.: dp-ucMGP ≥ 977 pmol/L or t-ucMGP ≤ 2825 nmol/L) were all identified as robust predictors of all-cause 5-year mortality. However, their co-incidence represented a substantial additional risk. We observed the highest mortality risk in patients with elevated BNP plus high dp-ucMGP compared to those with normal BNP plus low dp-ucMGP; fully adjusted HRR's were 4.86 (3.15-7.49). Likewise, the risk was increased when compared with patients with elevated BNP plus low dp-ucMGP; HRR 2.57 (1.60-4.10). Similar result we observed when co-incidence of elevated BNP and low t-ucMGP was analyzed [corresponding HRR's were 4.16 (2.62-6.61) and 1.96 (1.24-3.12)].. The concomitant abnormality of uncarboxylated MGP and mild elevation of BNP leads in chronic patients with vascular disease to about two-fold increase of the relative mortality risk. We hypothesize that abnormal homeostasis of MGP is involved in the pathophysiology of HF.

Topics: Aged; Biomarkers; Calcinosis; Calcium-Binding Proteins; Czech Republic; Extracellular Matrix Proteins; Female; Follow-Up Studies; Heart Failure; Humans; Male; Matrix Gla Protein; Prospective Studies; Risk Assessment; Risk Factors; Survival Rate; Vascular Diseases; Vitamin K

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

The percentage of time in therapeutic range (TTR) is a measure of anticoagulation quality with vitamin K antagonists (VKAs). The method most commonly used in clinical trials is the Rosendaal TTR. However, the application of this method in daily practice for clinical decision lacks appropriate instruments. We aimed to evaluate the percentage of tests within the target international normalized ratio (INR) (tests ratio) as a surrogate of Rosendaal TTR. We performed an observational and retrospective study to evaluate the TTR according to the Rosendaal method and tests ratio. We included all outpatients who attended the cardiology anticoagulation clinic of a Portuguese hospital (2011-2013), whose target INR was 2.0-3.0. Three hundred and seventy-seven VKA-treated patients followed for a mean 1.3 years were evaluated. Rosendaal methold and tests ratio significantly correlated (Rho Spearman 0.88, P < 0.001), but the Bland-Altman plot evaluation showed a clinically relevant data dispersion [95% confidence interval (95% CI) -12.9 to 23.1] around a mean difference in TTR -5.1% using the tests ratio method. The linear regression Passing-Bablok confirmed the existence of significant data dispersion and systematic differences. The tests ratio less than 60% had a sensitivity of 91.6%, specificity of 72.3%, positive predictive value (PPV) of 72.2% and negative predictive value (NPV) of 91.6%, for the diagnosis of patients inadequately anticoagulated (Rosendaal TTR <60%). Tests ratio had a c-statistics of 0.94 (95% CI 0.91-0.96). Number of tests in 6 months had a c-statistics of 0.70 (95% CI 0.65-0.75). Tests ratio underestimated TTR in 5% and was not considered equivalent to Rosendaal TTR due to the high variability between methods. Nevertheless, the use of tests ratio less than 60% may be a reasonable option to detect inadequate anticoagulation, as it is a sensitive method and excluded most of the patients with adequate control.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; International Normalized Ratio; Linear Models; Male; Outpatients; Predictive Value of Tests; Retrospective Studies; Stroke; Venous Thromboembolism; Vitamin K

Heart failure (HF) has been associated with an elevated international normalized ratio (INR) in patients on warfarin.. Compare warfarin sensitivity during hospital admission for HF exacerbation and chronic obstructive pulmonary disease (COPD) exacerbation with admissions unrelated to HF or COPD (controls) as well as during disease stability.. We conducted a case-controlled observational study. Patients admitted to a tertiary teaching hospital for HF exacerbation (n = 37), COPD exacerbation (n = 26), and admissions unrelated to HF or COPD (controls, n = 60) were included. Warfarin sensitivity (INR per daily mg dose of warfarin) at admission was compared to periods of disease stability and also compared between the 3 groups.. The increase in warfarin sensitivity at admission was 94% for HF patients (P < 0.0001), 59% for COPD (P = 0.003) patients, and 24% for controls (P = 0.002). HF patients with New York Heart Association (NYHA) class 3 and 4 and NYHA class 1 and 2 experienced changes in warfarin sensitivity of 125% (P = 0.006) and 50% (P = 0.13) at admission. HF patients had higher warfarin sensitivity at admission (mean = 1.62 [SD = 1.27]) compared to the control group (0.91 [0.52], P < 0.0001) and COPD group (1.03 [0.79], P = 0.04). and required greater intervention with vitamin K than controls (14% vs 0%, P = 0.007).. HF and COPD patients were more sensitive to warfarin during disease exacerbation, with HF exacerbation having the largest impact, resulting in clinically significant management implications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Disease Progression; Female; Heart Failure; Hospitalization; Humans; International Normalized Ratio; Male; Pulmonary Disease, Chronic Obstructive; Vitamin K; Warfarin

Topics: Aged; Anesthesia, General; Anticoagulants; Appendicitis; Blood Coagulation Disorders; Blood Coagulation Factors; Cardiomyopathy, Dilated; Consciousness Disorders; Female; Heart Failure; Heart Ventricles; Heart-Assist Devices; Hemostatics; Humans; International Normalized Ratio; Male; Middle Aged; Postoperative Care; Postoperative Complications; Tomography, X-Ray Computed; Vitamin K

Topics: Administration, Oral; Algorithms; Anticoagulants; Biomarkers; Chronic Disease; Clinical Laboratory Techniques; Diagnostic Imaging; Embolectomy; Endovascular Procedures; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Heart Failure; Home Care Services; Humans; Hypertension, Pulmonary; Long-Term Care; Neoplasms; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Pulmonary Embolism; Risk Factors; Vasoconstrictor Agents; Vasodilator Agents; Vitamin K

We report a familial form of ventricular non compaction in a mother and two of her sons. It was a young man of 25 years who presented with NYHA stage III dyspnea and a cough with bloody sputum. The clinical examination found left ventricular failure. The echocardiogram done showed left ventricular dilatation with large trabeculae separated by deep intertrabecular recesses in both ventricles suggestive of a non-biventricular compaction. It was possible to note from the family screening by echocardiography of the mother and half-brother a left ventricular non compaction while they were asymptomatic. Thus we concluded a familial form of ventricular non-compaction. This is the first familial case described in Senegal.

Topics: Adult; Barth Syndrome; Cardiovascular Agents; Developing Countries; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Senegal; Stroke Volume; Ultrasonography, Doppler, Color; Vitamin K; Young Adult

RECORDAF is the first worldwide, prospective, observational survey of management of atrial fibrillation (AF) in unselected, community-based patients.. Primary outcomes were therapeutic success and clinical outcomes associated with rhythm-control and rate-control strategies.. Patients with recent-onset AF were included (n = 5,604). Treatment strategy (rhythm control or rate control) was noted at baseline. Follow-up was 12 months. Therapeutic success required that strategy was unchanged without clinical events. Further maintenance of sinus rhythm was required in the rhythm-control group, and heart rate ≤80 beats/min in the rate-control group.. Data from 5,171 patients were assessable. Therapeutic success was 54% overall (rhythm control 60% vs. rate control 47%), a result driven by control of AF: rhythm control, 81% vs. rate control, 74%. After adjustment for propensity score quintiles, the rhythm-control strategy was significantly related to superior therapeutic success (odds ratio: 1.34, 95% confidence interval: 1.15 to 1.55; p = 0.0002). Clinical events occurred in 18% of patients. The arrhythmia management strategy was not predictive of clinical events. The type (persistent), presence at baseline visit, and duration (>3 months) of AF, together with age older than 75 years and the presence of heart failure, predicted progression to permanent AF. The choice of rhythm control reduced the likelihood of AF progression (odds ratio: 0.20, 95% confidence interval: 0.17 to 0.25; p < 0.0001).. Clinical outcomes in AF patients were driven mainly by hospitalizations for arrhythmia/proarrhythmia and other cardiovascular causes, but not by the choice of rate or rhythm strategy. Rhythm-control patients progressed less rapidly to permanent AF.

Topics: Age Factors; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Cardiac Glycosides; Catheter Ablation; Disease Progression; Electric Countershock; Electrocardiography; Female; Heart Failure; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Pacemaker, Artificial; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Registries; Stroke; Time Factors; Vitamin K

Coumarin anticoagulants impair the biological activity of the vitamin K-dependent procoagulant and anticoagulant proteins. There are no reports that focus on the levels of these proteins in over-anticoagulated patients. Therefore, we determined the levels of factor II, factor VII, factor IX and factor X, protein C and protein S in 25 randomly selected over-anticoagulated patients (International Normalized Ratio >/= 6.0) and in 25 matched, therapeutically anticoagulated patients with an International Normalized Ratio within the therapeutic zone. Furthermore, to study a possible effect of the cause of over-anticoagulation, coagulant levels were compared between 16 over-anticoagulated patients with fever in the preceding 2 weeks and 24 over-anticoagulated patients with stable congestive heart failure. The pattern of procoagulant level reductions in the three groups of over-anticoagulated patients was largely the same as in therapeutically anticoagulated patients: factor X was the lowest and factor IX the highest. The difference was that, in over-anticoagulated patients, factor VII was relatively low among the procoagulant factors compared with therapeutically anticoagulated patients. Protein C was lower than protein S in over-anticoagulated patients with congestive heart failure, but was similar to protein S in the other study groups. In over-anticoagulated patients with fever, the vitamin K-dependent coagulation proteins except factor X were significantly lower than in over-anticoagulated patients with congestive heart failure, especially factor VII and protein S.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factor Inhibitors; Blood Coagulation Factors; Case-Control Studies; Coumarins; Drug Overdose; Female; Fever; Heart Failure; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Vitamin K

A 17-year-old patient with Shone's disease had to be readmitted to the hospital 3 months after implantation of an artificial aortic valve because of extreme mitral insufficiency with consecutive pulmonary edema and hepatic dysfunction. He had been orally anticoagulated and presented with a high international normalized ratio of 6.7. Emergency replacement of the mitral valve was possible only after administration of prothrombin-complex concentrate, as vitamin K(1) and fresh frozen plasma did not correct the hemostatic defect sufficiently.

Topics: Adolescent; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Blood Coagulation Factors; Coagulation Protein Disorders; Emergencies; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Liver Diseases; Male; Mitral Valve Insufficiency; Mitral Valve Stenosis; Plasma; Pulmonary Edema; Radiography; Thromboembolism; Ventricular Outflow Obstruction; Vitamin K

The authors report a series of 47 patients treated with anticoagulants during pregnancy. The commonest indication was the presence of an artificial heart valve (72.3% of cases), most often mitral (58.9%). Thirty seven women were treated with heparin (group I) and ten with oral anticoagulants (OA) (group II) during the first three months. There was one peripheral venous thrombotic event and 2 post-partum deaths. Obstetric complications were equally distributed between the 2 groups, with the exception of spontaneous abortions during the first three months and fetal deaths, which were commoner with OA. Hemorrhagic complications occurred in 17% of cases at the time of delivery and during the immediate post-partum period. One case of coumarin embryopathy was seen. This series confirms that three periods are dangerous in the context of anticoagulant treatment during pregnancy: the first three months, delivery and postpartum. We recommend the use of heparin during the first three months and at the end of pregnancy, restricting OA to the period between 4 and 9 months.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Atrial Fibrillation; Female; Heart Failure; Heart Valve Prosthesis; Heparin; Humans; Indenes; Pregnancy; Pregnancy Complications; Thrombophlebitis; Vitamin K

A 1,760-G MALE INFANT SURVIVED MASSIVE PUlmonary hemorrhage. The literature is reviewed and the pathophysiologic changes and pathologic findings of this usually lethal complication of prematurity are discussed. Aggressive pulmonary toilet and ventilation seems warranted for these infants.

Topics: Asphyxia; Atropine; Blood Transfusion; Furosemide; Heart Failure; Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Male; Respiration, Artificial; Vitamin K

Topics: Anti-Arrhythmia Agents; Anticoagulants; Antihypertensive Agents; Diuretics; Drug Interactions; Drug Tolerance; Heart Failure; Humans; Hypolipidemic Agents; Intestinal Absorption; Tolbutamide; Vitamin K; Vitamin K Deficiency

Topics: Angina Pectoris; Anticoagulants; Blood Coagulation Disorders; Drug Synergism; Ethanol; Female; Follow-Up Studies; Heart Failure; Humans; Long-Term Care; Male; Myocardial Infarction; Vitamin K

Topics: Diuretics; Heart Failure; Thioctic Acid; Vitamin A; Vitamin K; Vitamins

Topics: Coumarins; Dicumarol; Heart Failure; Humans; Sexually Transmitted Diseases; Vitamin K