Atrial fibrillation and thromboembolism

Author arrhythmia

2019-04-22

Atrial fibrillation (often called “A-fib” or AF) is the most common type of heart rhythm disorder. In a normal heartbeat, the four heart chambers work evenly and rhythmically. In atrial fibrillation, disorganized electrical signals cause trembling of the two upper chambers of the heart (atria), with a frequency of more than 300 beats per minute and irregularly.

Atrial fibrillation (atrial fibrillation, AF) is the most common cardiac arrhythmia in the population and is especially common in patients with cardiovascular diseases. AF is often found in western countries, as the risk of developing the disease increases with age. In addition, AF has a negative social impact because it is associated with stroke and myocardial infarction.

Thrombosis that occurs in the appendage of the left atrium with subsequent embolism in the cerebral circulation, is considered the most important cause of ischemic stroke.

In addition to thromboembolism, AF is characterized by a combination of atherosclerotic risk factors, including hypertension, dyslipidemia, and diabetes, which may predispose to serious clinical complications of atherosclerosis, such as myocardial infarction. Moreover, if various tests of oral anticoagulants, such as warfarin, reduce the risk of stroke by about 60%, patients with AF still show an increased residual cardiovascular risk, which can seriously complicate the clinical course and treatment of AF

Video: Atrial Fibrillation (AF) Pathology

Features of thromboembolism and atherothrombosis in atrial fibrillation

An AF clinic is often complicated by ischemic manifestations, which usually affect cerebral circulation. The clinical characteristics of ischemic stroke developed on the background of AF can be quite serious, and thromboembolism plays an important role in this process.

In addition to thromboembolism, atrial fibrillation is characterized by a combination of atherosclerotic risk factors that can lead to serious complications, such as myocardial infarction. For this reason, AF is a kind of clinical situation where coronary heart disease may depend on either a thromboembolism, or atherothrombosis, or on both.

The different development associated with these two types of cardiovascular diseases allows the use of new strategies for treating AF, since clot management and platelet activation may be important to improve the prognostic finding.Therefore, a lot of attention today is paid to the mechanisms that can explain thromboembolism and atherothrombosis, as well as a new approach to the treatment of thromboembolism. In particular, it focuses on the still unsatisfied optimization of anticoagulant therapy.

Thromboembolism

For many years, the clinical events associated with thrombosis, mainly due to the formation of blood clots in the left atrium, followed by embolization in the cerebral and peripheral circulation.

AF meets the criteria for the Virchow triad, which are necessary for the formation of a blood clot:

  • Blood stasis
  • Endothelial dysfunction.
  • Activation of the coagulation system.

Blood stasis most often occurs in the left atrium in patients with AF, where the blood flow rate decreases markedly at the same time as the contractility of the appendage of the left atrium is impaired. However, it is still unclear whether the blood stasis associated with remodeling actually affects the formation of thrombus in AF.

Endothelial dysfunction is another important component of the Virchow triad. It has been found in patients with AF by measuring several markers of endothelial disorder, such as von Willebrand factor (vWf) and E-selectin.

  • vWf is a glycoprotein secreted by endothelial cells in response to damage. It is usually measured to assess damage to the endothelium.
  • E-selectin is an adhesive molecule that is specific for endothelial cells. This indicator is increased in the blood circulation as a result of the activation of the endothelium.

It is worth pointing out that the relevance of endothelial dysfunction in the context of clinical events associated with thrombosis was investigated in 423 patients with AF, who were under observation for about 2 years. At the end of the observation period, patients with elevated levels of vWf and E-selectin had a higher risk of cardiovascular events. This suggests that endothelial dysfunction may contribute to poor clinical outcome in this situation. [“The prognostic role of von Willebrand factor in plasma and soluble E-selectin levels for future cardiovascular events in a cohort of patients from the“ real world ”with atrial fibrillation.”
Krishnamurty S, Khoo CW, Lim H.S., Lane DA, Pignatelli P, Basili S, Violi F, Guba G.Yu. Eur J Clin Invest. October 2013;43 (10): 1032-8]

Activation of blood coagulation is the third component of the Virchow triad, which can contribute to the development of a thrombosis clinic in AF. Several studies have shown that AF can cause a hypercoagulable state, as evidenced by increased plasma levels of D-dimer and fibrinogen.

Atherothrombosis

Patients with AF usually identify various risk factors for atherothrombosis, including hypertension , which can be found in about 70-80% of the population; Other risk factors are diabetes and hypercholesterolemia . Patients with AF often show signs of atherosclerosis due to an atherosclerotic plaque, which significantly increases the risk of stroke compared with those who do not have a plaque.

Peripheral arterial disease (PAD) is an established marker of systemic atherosclerosis, which leads to an increased risk of myocardial infarction and stroke. In one study, the prevalence of ZPA in AF was found to be a link between AF and ZAP in the range from 4% to 16%.

Platelets play a key role in the process of atherothrombosis and the appearance of its clinical complications. The role of platelets in the development of ischemic events in AF was also investigated by several authors. Thus, when AF was found to be elevated:

  • P-selectin.
  • Beta-thromboglobulin.
  • Soluble CD40L (sCD40L).
  • All platelet activation markers.

Some studies indicate that patients with sCD40L are more likely to suffer from ischemic events, indicating the role of platelet activation in the clinical progression of AF.

Video: Thromboembolism Prevention in Atrial Fibrillation - CHA2DS2-VASc Score

Atrial Flicker Development Mechanism

With AF, a continuing prothrombotic state is detected, which includes clotting and platelet activation, but the underlying mechanism is still undetermined. There are suggestions that the development of atrial fibrillation is associated with systemic inflammation and an oxidative process. Not only can they contribute to the progression of the prothrombotic state through activation of the endothelium, platelets and coagulation, but electrical changes can also be triggered, ultimately leading to AF.

When AF is determined by several markers of inflammation:

  • C-reactive protein (CRP).
  • Alpha tumor necrosis factor.
  • Interleukin 2.6 and 8.
  • Protein-1 monocyte chemoattractant.

It should be noted that CRP is also associated with spontaneous echocardiographic contrast of the left atrium / appendage of the left atrium or thrombus, confirming the concept of the interaction of inflammation and thrombosis in AF.

The mechanisms that cause inflammation and oxidative stress can only be a matter of time. AF is characterized by systemic signs of atherosclerosis, which are themselves associated with inflammation. Also, increased regulation of nicotinamide-adenine dinucleotide phosphate oxidase (NOX) and “unbound” nitric oxide synthase (NOS) in the atria of patients prone to AF may reflect a process of systemic inflammation associated with the atherosclerotic process. Thus, it is assumed that atherosclerosis gradually reduces the blood supply to the myocardial tissue and causes atrial damage, which ultimately leads to premature myocyte apoptosis, fibrous replacement, and electrical changes. All this leads to the development of a clinic of atrial fibrillation.

Classical atherosclerotic risk factors, such as hypertension, diabetes, dyslipidemia, and obesity , can contribute to structural and functional myocardial remodeling. It ultimately leads to atrial fibrosis and changes in electrical excitability of the upper chambers of the heart through the inflammatory process, including excessive production of reactive oxidants. These changes in combination with platelet activation can cause local / systemic inflammation. They can also contribute not only to local thrombosis in the left atrium, but also atherothrombosis that occurs in the systemic circulation.

Principles of Atrial Flicker Outcomes

Most often, on the background of AF, stroke and myocardial infarction develop due to thromboembolism. In view of this, physicians try, first of all, to prevent the occurrence of these life-threatening conditions in patients with AF.

  • Stroke

Treatment of AF is mainly aimed at reducing thromboembolic stroke with anticoagulants and / or antiplatelet agents.Thus, patients are divided into categories in which the best benefit from antiplatelet or anticoagulant therapy is obtained.

Evaluation of CHADS 2, which includes congestive heart failure, hypertension, age, diabetes and previous stroke, was first introduced to identify patients undergoing treatment with antithrombotic drugs (aspirin or oral anticoagulant).

In an attempt to better distinguish between patients with a low or high risk of stroke, a new CHA2DS2-VASc assessment has recently been introduced. It is characterized by the inclusion of two age limits, female and vascular diseases as independent risk factors for the development of stroke. With its help, patients with AF are divided into two categories:

  • Patients with low risk (score 0-1).
  • Patients with high risk (score ≥2) of future cerebrovascular events.

In fact, while patients with AF for CHADS2-VASc score 0 are not candidates for any antithrombotic prophylaxis (patients with low risk), those with CHA2DS2 -VASc score 1 can be treated with oral anticoagulants or, in as an alternative, aspirin . Finally, all patients with AF for CHA2DS2-VASc ≥2 should receive vitamin K anticoagulant therapy with oral antagonists or new oral anticoagulants in the absence of contraindications to such treatment.

On a global scale, studies with anticoagulants clearly demonstrated a clear advantage, which in fact was confirmed by a 68% reduction in risk compared with untreated patients.

The only concerns are related to the complication of bleeding, especially in the brain, blood monitoring and insufficient use of Vicasol. For this reason, the development of other drugs, such as dabigatran etexilate, a direct inhibitor of thrombin, and inhibitors of factor Xa by the type of rivaroxaban, apixaban and edoxoban, is given.

Although these drugs significantly expand the possibilities of medical exposure, at present, new oral anticoagulants (new oral anticoagulants, NOAC) are not suitable for all patients with AF, so the doctor will always take some caution into account before prescribing them.

Even if it is believed worldwide that NOAC reduces the likelihood of developing cardiovascular complications against the background of AF, additional studies have shown that low-dose NOAC regimens can reduce the risk of hemorrhagic stroke, but not as effectively as warfarin taken to prevent ischemic stroke and myocardial infarction.

Another point that should be taken into account concerns the use of NOAC by patients with renal insufficiency. In particular, people with severe renal insufficiency (with glomerular filtration of less than 30 ml / min) and / or on dialysis were not included in clinical trials, therefore, in such cases, treatment with oral vitamin K antagonists is still recommended. K antagonists, VKAs).

  • Myocardial infarction

The management of patients with atrial fibrillation in a risk group or with a previous myocardial infarction is a new hot topic today. It should be resolved soon, since the prevention of myocardial infarction in case of AF can reduce the risk arising from the combination of oral anticoagulants with aspirin.

Statins can be used to prevent adverse effects, as they reduce the risk of myocardial infarction during primary and secondary prophylaxis. In addition, statins have antithrombotic properties that may be useful during the treatment of patients with AF, especially in the presence of systemic and local prothrombotic conditions. Statins are usually used to:

  • Reducing the likelihood of a new attack of AF.
  • Preventing recurrence of AF after electrical cardioversion / ablation.
  • Prevention of complications after cardiac surgery.
  • Treatment of patients with acute coronary syndrome.

However, the effect of statin use to reduce vascular manifestations in patients with AF is not fully confirmed, since it has never been studied in prospective randomized trials.

Conclusion

Atrial fibrillation and thromboembolism are closely related, as the development of the first disease increases the risk of blood clots, which in turn can lead to stroke or myocardial infarction.

The mechanism of development of thromboembolism and atrial fibrillation is in the process of being studied. At the same time, new drugs have been developed that are suitable for treating those categories of patients to whom conventional anticoagulants are not suitable.

NOAC is likely to be a step forward in the treatment of AF, since they can greatly reduce the number of patients who cannot take conventional anticoagulants or similar treatment is inadequate.

Finally, patients with AF who are at risk or have MI should be under medical observation, since there is another serious problem that deserves close attention. This is primarily due to the fact that in elderly patients with AF, the likelihood of developing MI is higher, despite the use of oral anticoagulants.

Video: Thromboemboli and thromboembolisms | Miscellaneous | Heatlh & Medicine | Khan Academy


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