ANTICOAGULANT THERAPY IN HEART DISEASE—A Summary of the Literature

Considerable experience by many independent workers with the use of anticoagulants in the treatment of certain types of heart disease has shown that such therapy reduces significantly the incidence of thromboembolic complications and, largely through this effect, the morbidity and mortality rate from heart disease of these types.This is certainly established in acute coronary occlusion with myocardial infarction and in those instances of rheumatic heart disease with auricular fibrillation in which repeated embolic phenomena have occurred. The case for the administration of the anticoagulants in congestive heart failure is less secure, although there is no doubt that the number of thromboembolic complications is reduced by use of them.The administration of the anticoagulants requires considerably more exacting attention than does the administration of the majority of therapeutic agents in use commonly today. Hence, it is suggested that the use of anticoagulants in heart disease be restricted to those instances in which the indications are clear and facilities are compatible with the efficient and safe use of the drug, whether Dicumarol or heparin.     

Heterozygous protein C deficiency type I

Protein C is a vitamin K-dependent plasma protein which has anticoagulatory and profibrinolytic properties as a result of inactivating coagulation factors Va and VIIIa and enhancing fibrinolysis. Heterozygous protein C deficiency is well known to be a risk factor for thromboembolic diseases. We here present a family with 16 members deficient in protein C, out of which only two persons were suffering from thromboembolic disorders. In patients suffering from heterozygous protein C deficiency thromboembolic complications in childhood are rare and are not obligatory in adults. These patients should therefore not be treated with oral anticoagulants unless thromboembolic complications have already occurred or are imminent. Coumarin anticoagulation implicates a serious risk of coumarin skin necrosis in protein C deficient patients during the initial therapeutic phase. This risk may be avoided by initiating coumarin therapy with low doses of the drug and in cases of thromboembolic complications by overlapping with heparin anticoagulation.     

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants versus Vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation: A Meta-Analysis

BackgroundUse of the non-vitamin K antagonist oral anticoagulants (NOACs) is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF). However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA) of AF has not been well established yet.ObjectivesTo perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs) in patients undergoing RFCA.ResultsThere was no significant difference in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001). Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41; p=0.01) events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).LimitationsAs with every meta-analysis, no patients-level data were available.

Conclusions and Implications

The use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no significant benefit on onset of thromboembolic events.     

Long-term anticoagulation. Indications and management.

Each year half a million persons in the United States receive long-term anticoagulant therapy to prevent venous and arterial thromboembolism. Unfortunately, the relative benefits and risks of anticoagulant therapy have not been adequately quantified for many thromboembolic disorders, and the decisions as to whether, for how long, and how intensely to administer anticoagulation are often complex and controversial. Several expert panels have published recommendations for anticoagulant therapy for different thromboembolic disorders; the primary area of disagreement among these panels concerns the optimal intensity of anticoagulation. Recent research and analytic reviews have helped to clarify both the risk factors for and the appropriate diagnostic evaluation of anticoagulant-induced hemorrhage. Clinicians must be aware of the nonhemorrhagic complications of anticoagulant therapy, particularly during pregnancy. The administration of anticoagulants is difficult both in relation to dosing and long-term monitoring. Knowledge of the pharmacology of the anticoagulants, an organized approach to ongoing monitoring, and thorough patient education may facilitate the safe and effective use of these drugs.     

CONGESTIVE HEART FAILURE IN INFANTS AND CHILDREN

Congestive failure in infants and children is not uncommon and may be present in a varying number of conditions, particularly in certain types of congenital heart disease. Its recognition and proper treatment are usually followed by improvement, except in those instances where the failure is associated with a lesion incompatible with life. The essentials of treatment are: Treatment of the underlying cause, administration of a digitalis preparation, low salt diet, diuretics, rest and sedation, oxygen, adequate diet and, in rare instances, the use of steroids.     

ACUTE MYOCARDIAL INFARCTION—A Discussion of Certain Controversial Issues

As a general rule, it is not believed possible to classify patients with acute myocardial infarction as to the future severity of their illness at the time of the initial examination. However, classifications are possible from complete clinical data of the first few days with regard to the predicted mortality rates. Whether to manage the patient in the hospital or at home depends on the community facilities. The patient should be in bed for a period of two to three weeks if unquestioned infarction has occurred.The main avenue of investigation as to lowering of mortality needs to be directed toward the prevention of heart failure or sudden unexpected death probably related to arrhythmia. If the patient is hospitalized and laboratory facilities are available, anticoagulant therapy can be safely and effectively carried out without undue risk or prohibitive increase in the cost of management. The experience of the author and his colleagues has led to the belief that anticoagulants given routinely to patients with myocardial infarction are effective in decreasing the incidence of thromboembolic complications.     

Relation of trauma to disease; aspects of correlation in cases involving compensation

As a general rule, it is not believed possible to classify patients with acute myocardial infarction as to the future severity of their illness at the time of the initial examination. However, classifications are possible from complete clinical data of the first few days with regard to the predicted mortality rates. Whether to manage the patient in the hospital or at home depends on the community facilities. The patient should be in bed for a period of two to three weeks if unquestioned infarction has occurred. The main avenue of investigation as to lowering of mortality needs to be directed toward the prevention of heart failure or sudden unexpected death probably related to arrhythmia. If the patient is hospitalized and laboratory facilities are available, anticoagulant therapy can be safely and effectively carried out without undue risk or prohibitive increase in the cost of management. The experience of the author and his colleagues has led to the belief that anticoagulants given routinely to patients with myocardial infarction are effective in decreasing the incidence of thromboembolic complications.     

Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study.

OBJECTIVE--To assess the risk of cerebral thromboembolism in women using low dose oral contraceptives. DESIGN--A retrospective case-control study. SETTING--All Danish medical, neurological, neurosurgical, and gynaecological departments. SUBJECTS--All 794 women in Denmark aged 15-44 who had suffered a cerebral thromboembolic attack during 1985-9 and 1588 age matched randomly selected controls. RESULTS--Of 692/1584 case/control questionnaires sent out, 590/1396 (85.3%/88.1%) were returned. Among the cases, 15 refused to participate, 69 had a revised or unreliable diagnosis, 40 had had thromboembolic disease previously, 13 were pregnant, and 152 had a disease predisposing to a cerebral thromboembolic attack. Of the 323 cases without a known predisposition, 320 reported use or non-use of oral contraception. Among the 1396 controls, eight refused to participate, were mentally retarded, or lived abroad; 18 returned an uncompleted questionnaire; 17 had had thromboembolic disease previously; 31 were pregnant; and 130 had a disease predisposing to a cerebral thromboembolic attack. Thus 1198 non-predisposed controls were available, among whom 1197 reported use or non-use of oral contraception. Among the 320 cases, 116 (36.3%) were oral contraceptive users at the time of the cerebral thromboembolic attack. By comparison there were 191 users (16.0%) among the 1197 controls, giving a crude odds ratio of 3.0. After multivariate analysis, including confounder control for age, smoking, years of schooling, and trend in use of different types of oral contraceptives during 1985-90, pills containing 50 micrograms oestrogen were associated with an odds ratio for cerebral thromboembolic attack of 2.9 (95% confidence interval 1.6 to 5.4), those containing 30-40 micrograms oestrogen an odds ratio of 1.8 (1.1 to 2.9), those containing progestogen only an odds ratio of 0.9 (0.4 to 2.4). The odds ratio did not change with increasing age or with duration of oral contraceptive use. A 50% increased risk of a cerebral thromboembolic attacks among cigarette smokers (after confounder control) was independent of oral contraception status and age. CONCLUSION--Low dose oral contraceptives are associated with an increased risk of cerebral thromboembolic attack. Combined or sequential pills containing 30-40 micrograms oestrogen are associated with a one third reduced risk compared with preparations containing 50 micrograms oestrogen. Progestogen only pills did not increase the risk of a cerebral thromboembolic attack.     

Cancer chemotherapy and anticoagulant prophylaxis

The modern pathobiochemical explanation of the old clinical finding, i.e. that the occurrence of the thromboembolic complications in cancer patients is significantly higher, starts to be clarified on the basis of recent knowledge regarding the role of cancer procoagulant, the expressed tissue factor and the changes in the clotting and fibrinolytic systems. Furthermore, the presently used chemotherapeutic agents have activating effects of the coagulation system as well. The details of these phenomena, the frequently used drugs and their pathobiochemical effects are detailed in this publication. Finally, it gives an outlook regarding the new adjuvant, beneficial effects of the direct anticoagulants in malignancies.     

INDICATIONS FOR ANGIOCARDIOGRAPHY

Angiocardiography is indicated in selected cases of heart disease in which a definite diagnosis cannot be made by ordinary methods or in which there is reasonable expectation that the information so obtained may influence the treatment of the patient. Whenever possible, angiocardiography should be done in conjunction with cardiac catheterization. The main indication for angiocardiography is cyanotic congenital heart disease; primarily those cases in which there is a right-to-left shunt. Angiocardiography is occasionally of value in diagnosis of other types of congenital heart disease and in acquired heart disease.     

Optimal long-term antithrombotic management of atrial fibrillation: life cycle management

Optimal antithrombotic management of atrial fibrillation equals balancing between prevention of arterial thromboembolism, predominantly ischaemic stroke, and haemorrhagic complications. Over time different antithrombotic agents and strategies have been developed. At present, non-vitamin K antagonist oral anticoagulants (NOACs) are the first-line therapy for stroke prevention in patients with non-valvular atrial fibrillation (i.e. without a mechanical valve prosthesis or rheumatic heart disease). Considering the impact of the suboptimal adoption of recommended oral anticoagulant therapy, as experienced with the previous first-line vitamin K antagonists, this review focuses on adequate use of NOACs. As such, we address the most important and clinically challenging issues in the antithrombotic life cycle management for long-term stroke prevention in atrial fibrillation.     

Heart valve prosthesis, anticoagulants and pregnancy

Patients with artificial valve prostheses require lifelong anticoagulation treatment. The risk of thrombotic complications increases greatly in pregnancy. Anticoagulant treatment in pregnant women with artificial heart valve prostheses in one of the most controversial problems in medical practice as anticoagulants which are beneficial and safe for the mother may by hazardous for the fetus. Recommended procedure is to administer heparin subcutaneously at last during the first 14 weeks and the last 2 weeks of gestation and coumarin derivates throughout the second and third trimesters. In asymptomatic or mildly symptomatic women who are willing to follow a strict regimen of antithrombotic prophylaxis in pregnancy the risk is not associated with an increased morbidity or mortality in the mother or fetus. Hence, recommendations against pregnancy in women with artificial heart valves are not always justified.     

Antihyperlipidemic and antioxidant effects of feather protein hydrolysate in high‐fat diet‐fed mice

The hyperlipidemia is a serious health problem that increases the risk of many complications including cardiovascular disease. This study aims to evaluate the possible antihyperlipidemic effects of the feather protein hydrolysate (FPH) in a mice fed with a high‐fat diet (HFD)‐fed mice during 5 weeks. The FPH administration improved dose‐dependent lipid profile, as well as the liver and renal dysfunction indices in hyperlipidemic mice. The FPH also restored the antioxidant status in liver, kidney, and heart by lowering the lipid peroxidation and enhancing the antioxidant enzymes (catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase [SOD]). Moreover, the histological studies proved that FPH administration prevents hepatic steatosis, glomerular hyperfiltration risk, and cardiac muscle hypertrophy. Accordingly, the FPH is a promising novel medicinal ingredient for possible use in the hyperlipidemic treatment and related complications.     

Free emboli formation in the wake of bi-leaflet mechanical heart valves and the effects of implantation techniques

The high incidence of thromboembolic complications of mechanical heart valves (MHV), primarily due to platelet activation by contact with foreign surfaces and by non-physiological flow patterns past the valve, still limits their success as permanent implants. The latter include elevated shear and turbulent stresses and shed vortices formed in the wake of the valve's leaflets during the deceleration phase, potentially entrapping activated and aggregated platelets. It is hypothesized that these flow patterns induce the formation of free emboli which are the source of cerebrovascular microemboli associated with MHV. Implicit to this hypothesis is that free emboli formation will be affected by the implantation technique employed and the valve orientation, as those will alter the flow characteristics past the valve and the interaction of the platelets with the flow. In this study, numerical simulations of turbulent pulsatile flow past a St. Jude Medical bi-leaflet MHV were conducted. Platelet shear histories were calculated along pertinent turbulent platelet trajectories, and the effect of a misaligned valve on platelet activation was quantified and compared to that of an aligned valve. It demonstrated that the combination of a tilted valve and subannularly sutured pledgets had an explicit detrimental effect on platelet activation, with the following entrapment of the platelets within the shed vortices of the wake leading to a significant increase of the thromboembolic potential of the valve. This numerical model depicted a viable course for free emboli formation, and indicated how the implantation technique may enhance the risk of cardioembolism.     

MANAGEMENT OF PERIPHERAL ARTERIAL OCCLUSIVE DISEASE

The proper use of medical therapeutic agents in the management of peripheral arterial occlusive disease must be based upon a thorough understanding of the factors controlling vasomotor tone and vasospasm, mechanisms regulating blood flow in skin and muscle, factors favoring nutritional and shunt flow, effects of the diversion of blood from one vascular bed to another, muscle contraction as a factor which may limit the blood flow to a part, epinephrine sensitivity after sympathectomy, and the effects of vasodilator drugs on the local and total circulations.There are six major classes of therapy for peripheral arteriosclerosis: General medical care, administration of vasodilator drugs and administration of anticoagulants, sympathectomy, direct vascular operation and amputation. In many cases the most successful treatment is a combination of medical and surgical therapy.     

Assessment of Short-term Anticoagulant Administration after Cardiac Infarction

This report describes the design and results of a controlled trial of anticoagulant drugs in the treatment of patients admitted to hospital suffering from acute myocardial infarction. A total of 1,427 patients were allocated at random to therapy with high-dosage or low-dosage anticoagulants. The high-dosage regimen was 36 hours of heparin administration and phenindione in doses to maintain the thrombotest level between 10 and 20%. The mean phenindione dosage was 72 mg./day. The low-dosage regimen consisted of 1-mg. tablets of phenindione. Therapy was continued for 28 days.There was no significant reduction in the mortality in the high-dosage group. Among the 712 patients allocated to high dosage 115 (16·2%) died before the 29th day of the trial. Of the 715 patients allocated to low dosage 129 (18%) died. This difference between these mortality rates could have occurred by chance.There was a significant reduction in the frequency of clinically evident thromboembolic complications (systemic artery occlusion, leg vein thrombosis, and pulmonary embolism) among patients in the high-dosage group. This did not, however, materially affect the difference in mortality from all causes.     

Deep venous thrombosis and pulmonary embolus after face lift: a study of incidence and prophylaxis

Deep venous thrombosis and pulmonary embolus are known risks of surgery. However, the incidence of these conditions in face lift is unknown. In this study, the incidence of deep venous thrombosis/pulmonary embolus after face lift is studied and factors associated with thromboembolic complications are evaluated. One-third of the active members of the American Society for Aesthetic Plastic Surgery were randomly selected. Participating surgeons completed a one-page survey providing information on face-lift procedures during a 12-month study period. A response rate of 80 percent was achieved, with 273 of the 342 surgeons responding to the survey. A total of 9937 face-lift procedures were reported in the 1-year study period. There were 35 patients with deep venous thrombosis (0.35 percent), 14 patients with pulmonary embolus (0.14 percent), and 1 patient death in the series. Although 43.5 percent of patients underwent face lift under general anesthesia, 83.7 percent of deep venous thrombosis/pulmonary embolus events occurred with general anesthesia. For prophylaxis for deep venous thrombosis/pulmonary embolus, 19.7 percent of the surgeons used intermittent compression devices, 19.6 percent used thromboembolic disease hose or Ace wraps, and 60.7 percent used no prophylaxis. Of patients developing deep venous thrombosis/pulmonary embolus, 4.1 percent were treated prophylactically with intermittent compression devices, 36.7 percent with thromboembolic disease hose/Ace wraps, and 59.2 percent with no prophylaxis. It was found that deep venous thrombosis/pulmonary embolus after face lift is a measurable complication experienced by one of nine surgeons surveyed. Deep venous thrombosis/pulmonary embolus is more likely to occur when the procedure is performed under general anesthesia. The majority of plastic surgeons surveyed used no prophylaxis for deep venous thrombosis when performing face-lift procedures. Intermittent compression devices were associated with significantly fewer thromboembolic complications, whereas Ace wrap/thromboembolic disease hose afforded no protection against deep venous thrombosis/pulmonary embolus when used alone. In conclusion, aesthetic surgeons should consider adopting intermittent compression devices when performing face lift under general anesthesia.     

Continuation of vitamin K antagonists as acceptable anticoagulation regimen in patients undergoing pulmonary vein isolation

Background

Recent studies have demonstrated that radiofrequency isolation of the pulmonary veins (PVI) is an effective treatment for symptomatic atrial fibrillation. Based on these positive results, non- pharmacological therapy has been incorporated in the guidelines for drug refractory atrial fibrillation, resulting in an increased popularity. The prevention of thromboembolic complications remains an important issue.

Methods

In January 2010, we adopted an anticoagulation strategy based on continuation of vitamin K antagonists (VKAs) and selective use of transoesophageal echocardiogram (TEE). We retrospectively analysed the results of this strategy in all patients referred for PVI treatment. VKAs were started for all patients 2 months prior to treatment. Discontinuation of oral anticoagulation was considered 3 months after treatment based on thromboembolic and bleeding risk profile. Bleeding and thromboembolic complications were registered during outpatient clinic follow-up up until 3 months.

Results

We performed 151 PVI procedures from January 2010 to March 2011. All patients were seen 6 weeks after discharge. No transient ischaemic accidents or ischaemic cerebrovascular incidents occurred pre-, peri- or postprocedure. Four (2.7%) procedures were complicated by tamponade requiring pericardiocentesis.

Conclusions

Our data support the increasing evidence for continuation of periprocedural administration of VKAs complemented by a selective TEE approach as a safe therapy for thromboembolic complications.     

Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood

Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci--coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA)--were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans.     

Medical complications of obesity.

Obesity leads to several complications that affect many body systems. This paper focuses mainly on the cardiovascular complications, which include coronary heart disease, cerebrovascular disease and stroke, and congestive heart failure; the last may be secondary not only to advanced coronary atherosclerosis, but also to other pathogenetic factors. The increased frequency of coronary heart disease in the obese is largely attributable to the commonly associated hypertension, diabetes mellitus and lipoprotein abnormalities, rather than the adiposity. The lipoprotein disorders that have a role in atherogenesis are decreased plasma concentrations of high-density lipoproteins and elevated plasma concentrations of low-density lipoproteins. Abnormalities in cholesterol metabolism are responsible for the increased frequency of cholelithiasis in obese persons. The factors that mediate the development of cardiovascular and gallbladder complications are correctable by an appropriate program of meal planning and physical activity.