Historically, one landmark of societal progress has been the pattern of disease - specifically, the emergence of non-communicable diseases as significant health problems, replacing infections. Strokes may well represent the flagship of these non-communicable diseases. That said, it is worth mentioning that the heavy burden of stroke continues to be in low-to-middle-income countries. An estimated 26 million people suffer from a stroke every year, making it one of the most significant contributors to both mortality, and long-term disability. Up to two-thirds of these are ischemic. Approximately 25% of all ischemic cases are believed to be cardioembolic in origin. However, despite accounting for a relatively small proportion of all ischemic strokes, cardioembolic strokes are particularly important as they are frequently more severe than atherothrombotic strokes. Additionally, they are more prone to both early and late recurrences.
Cardioembolic strokes can occur from at least a dozen specific cardiac disorders which include atrial fibrillation, left ventricular thrombi, cardiac tumors, valvular vegetations, and paradoxical emboli. For the most part, cardioembolic strokes can be prevented.
Cardioembolic strokes can occur as a consequence of any cardiac insult that could cause the fulfillment of Virchow's triad of endothelial injury, stasis, and hypercoagulability.
Commonly encountered causes include:
Cardioembolic strokes appear to occur more frequently with increasing age. Studies have estimated that they account for 14.6% of cases below the age of 65 years, but this proportion has gone up to 36% for patients aged 85 years and older.
About 20% of strokes are considered to cardioembolic. The risk of these strokes increases with age.
As with any thrombus, the fundamental pathophysiology is vested within Virchow's triad. Stasis of blood, as occurs with ventricular akinesia or aneurysms predisposes to thrombus formation. Similarly, the lack of atrial contractility in atrial fibrillation results in an increased predisposition to clot formation, particularly in the left atrial appendage. These thrombi can either remain indolent and later undergo organization, or embolize to systemic circulation - stroke being one of the potential consequences. With atrial fibrillation, this risk is greatest when converting a patient back to sinus rhythm.
The endothelial injury that accompanies valvular lesions also predisposes to hypercoagulability and thrombus formation, with similar potential consequences.
The cardiac emboli may consist of cholesterol, thrombus, platelet thrombi, calcium, or even bacterial clumps. Emboli from the heart can be distributed anywhere in the body, but more than 80% migrate to the brain. Of the emboli to the brain, the majority involve the anterior circulation with only about 20% involving the vertebrobasilar circulation.
When emboli enter the brain, they not only obstruct blood flow but may become detached and migrate further distally. Thus, reperfusion is another form of injury.
The classic clinical scenario is that of an abrupt onset neurologic deficit, that reaches maximal intensity within minutes, and then gradually improves.
As with all strokes, the clinical features depend on the extent and location of neurovascular compromise. However, depressed consciousness is usually a factor favoring a cardioembolic etiology, as opposed to an atherothrombotic stroke. Further, eliciting a history of a Valsalva-like maneuver provoking the stroke also supports a cardioembolic etiology. Cardioembolic strokes cause more seizures due to distal ischemia.
Classic features of cardioembolic stroke include the following:
Cardiac findings may include:
The preliminary cardiac evaluation must be directed towards evaluating both the electrophysiologic status of the heart as well as structural and functional status. As such, workup must include a 12-lead ECG and transthoracic echocardiography for all patients.
Structural and Functional Assessment:
Although the imaging modality of choice will differ based on the time of presentation of the patient (i.e., within the window period or outside it), the following principles govern the process of evaluation:
Although most standard guidelines recommend against instituting this as a routine practice, the evaluation of patients for hyper-homocysteinemia secondary to metabolic vitamin B12 deficiency continues to have a role in the evaluation of a patient of stroke. This is particularly significant in patients known to be following a vegan lifestyle.
The cornerstone of the management of cardioembolic strokes involves the use of anticoagulants for secondary prevention.
However, the exact timing of the initiation of anticoagulation remains a matter of controversy. The intention is to strike a delicate balance the risk of recurrence on the one hand, and the risk of a hemorrhagic transformation of the infarct on the other.
Current guidelines propose an arbitrary deferral of anticoagulation for two weeks after the event, based on the extrapolation of trials based on heparin use.
Conventionally, vitamin K antagonists like warfarin are used for oral anticoagulation. Therapeutic response is monitored by serial assessment of prothrombin time and the international normalized ratio (PT/INR). The target INR is between 2.0 to -3.0. However, this target is scaled up to 2.5 to 3.5 for cases with metallic mitral valves. Although universally available and inexpensive, a poorly predictable dose-response curve, a penchant for drug interactions, and a heavy dependence on patient dietary compliance are key drawbacks of these agents.
Direct oral anticoagulants (DOACs) represent the new generation of oral anticoagulants that overcome the shortcomings of vitamin K antagonists. Available agents include apixaban, rivaroxaban, dabigatran, and edoxaban. These newer agents are believed to have a more predictable dose-response curve, and their use obviates the need for repeated monitoring. A key drawback of these DOACs was the lack of availability of a reversal agent; however, this is no longer always the case. Reversal agents for dabigatran (idarucizumab) and rivaroxaban and apixaban (recombinant factor Xa - Andexanet alfa) have received FDA approval and are available for clinical use.
Various devices have also received approval for stroke prevention, such as the "WATCHMAN" device for left atrial appendage closure. Such devices are useful in patients with atrial fibrillation unable to tolerate anticoagulation. By sealing off the left atrial appendage, these devices reduce the risk of atrial thrombi, that develop due to atrial fibrillation, embolizing into the systemic circulation.
Closure of the patent foramen ovale is also gaining recognition as a vital tool to prevent stroke recurrence. It has shown a clear superiority to antiplatelet therapy, and non-inferiority to anticoagulation. Any patient who had cardioembolic stroke less than 60 years old should evaluate for patent foramen ovale.
For patients with left ventricular thrombus and myocardial infarction, we usually recommend anticoagulation at least for three months due to embolization risk.
Atherothrombotic strokes must be excluded.
The TIMING study, undertaken in 2017, is likely to provide useful clinical information regarding the optimal time of initiation of anticoagulation.
If not treated appropriately, cardioembolic strokes have a higher tendency than atherothrombotic strokes to show both early and late recurrences.
Hemorrhagic transformations - both spontaneous and post-anticoagulation therapy - are potentially grave consequences of this condition. Long-term disability, bed-rest related complications such as pressure sores, may all occur, but vary depending on the severity and extent of neuro deficit.
Avoiding excessive alcohol, adopting a Mediterranean-like or DASH (dietary approaches to stop hypertension) diet, and other measures that can combat both hypertension, as well as eliminate triggers of atrial fibrillation, are likely to be beneficial.
Patients on warfarin should be provided with a list of foods that contain vitamin K (avocado, broccoli, etc) which can limit the efficacy of warfarin.
A cardioembolic stroke is a classic example of a problem that requires an interprofessional approach to solve. Most hospitals have an interprofessional team dedicated to the management of patients with stroke. This stroke team consisting of a cardiologist, a neurologist, a dedicated radiologist (potentially an interventional neuro-radiologist if thrombectomy is warranted), and an internal medicine physician is vital in improving outcomes. In addition, the pharmacist must educate the patient on the importance of drug compliance, discontinuing tobacco and abstaining from alcohol. If the patient has atrial fibrillation, a cardiology nurse must follow these patients to ensure that the INR is therapeutic. Neuroscience and stroke certified nurses are involved in patient care and education and report status changes to the team. Serial ECG and echocardiograms are recommended in these patients. The interprofessional team should communicate so that the patient is offered the current standard of care therapy.
Current evidence regarding when to initiate treatment is still sketchy [Level V]. Trials such as the TIMING study are likely to add valuable information to the existing knowledge base.
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