Ischemic Stroke & Transient Ischemic Attack 3

Question 1

What percentage of stroke is of cardioembolic origin?

Answer 1

30% of strokes

Question 2

Embolic stroke characteristics

Answer 2

An embolic mechanism is especially likely when neuroimaging reveals infarcts in multiple vascular territories or a single wedge-shaped infarct involving cortex and the underlying subcortical white matter.

With embolic stroke, the neurologic deficit is typically maximal from the onset, with a possibility of rapid improvement if there is spontaneous recanalization

Question 3

How do cardioembolic strokes progress and which is a possible consequence

Answer 3

Cardioembolic occlusions usually recanalize
(up to 90% are no longer visible on angiography after 48 hours)

This tendency to recanalize may contribute to the high frequency of hemorrhagic transformation after cardioembolic stroke

Question 4

High risk cardioembolic sources

(risk of recurrence)

Answer 4

Cardioembolic stroke AHA 2017

Question 5

Is PFO considered high risk cardioembolic source?

Answer 5

No

Question 6

What is the most common cause of cardioembolic stroke

Answer 6

Atrial Fibrillation

Question 7

Types of atrial fibrillation and secondary prevention

Answer 7

1) valvular AF (in the setting of moderate to severe mitral valve stenosis or mechanical valve replacement)

Warfarin

2) non-valvular AF

DOACs

Question 8

DOACs usual dosing

Answer 8

Question 9

Dabigatran mechanism of action

Answer 9

Το dabigatran είναι ένας δραστικός, ανταγωνιστικός, αναστρέψιμος άμεσος αναστολέας της θρομβίνης και είναι το κύριο δραστικό συστατικό στο πλάσμα.
Εφόσον η θρομβίνη καθιστά δυνατή τη μετατροπή του ινωδογόνου σε ινώδες κατά τη διεργασία της πήξης, η αναστολή της εμποδίζει τη δημιουργία θρόμβου.
Το dabigatran αναστέλει επίσης την ελεύθερη θρομβίνη, τη θρομβίνη η οποία είναι δεσμευμένη στο ινώδες και τη συγκόλληση των αιμοπεταλίων που προκαλείται από τη θρομβίνη.

Question 10

Apixaban: Clinical settings in which dose modification or drug avoidance may be indicated

Answer 10

Dose reduced to 2.5 mg twice daily for those with any two of the following:
* age ≥80 years
* body weight ≤60 kg
* serum creatinine ≥1.5 mg/dL

Apixaban dose reduction is recommended for patients who are also receiving strong dual inhibitors of CYP-3A4 and P-glycoprotein

Το Eliquis αντενδείκνυται σε ασθενείς με ηπατική νόσο σχετιζόμενη με διαταραχή της πήξης του αίματος και κλινικά σημαντικό κίνδυνο αιμορραγίας

Question 11

Differences in drug interactions between dabigatran, apixaban and rivaroxaban

Answer 11

Apixaban and Rivaroxaban:
Strong dual CYP3A4 and P-gp inhibitors can increase effect
Strong CYP3A4 inducers and/or P-gp inducers can decrease effect

ισχυροί αναστολείς τόσο του CYP3A4 όσο και της P-gp: αντιμυκητιασικά της ομάδας των αζολών (π.χ., κετοκοναζόλη, ιτρακοναζόλη, βορικοναζόλη και ποσακοναζόλη) και αναστολείς της πρωτεάσης του HIV (π.χ., ριτοναβίρη)

Iσχυροί επαγωγείς των CYP3A4 και P-gp: ριφαμπικίνη, φαινυτοΐνη, καρβαμαζεπίνη, φαινοβαρβιτάλη ή St. John’s Wort)

Dabigatran:
P-gp inhibitors can increase dabigatran effect
P-gp inducers can decrease dabigatran effect

Examples of P-gp inhibitors include: clarithromycin, ombitasvir- or ritonavir-containing combinations, and verapamil.
Examples of P-gp inducers include: phenytoin, rifampin, and St. John’s wort.

Question 12

Expected effects of anticoagulant drugs on commonly used coagulation tests

Answer 12

++ Thrombin time:
Heparin, LMW heparin, and direct thrombin inhibitors (eg, bivalirudin or argatroban) will prolong the TT.
In contrast, oral direct Xa inhibitors, danaparoid, fondaparinux, and warfarin do not prolong the thrombin time.

Question 13

When to use Warfarin in AF

Answer 13

Exceptions to the general preference for use of DOAC rather than VKA in patients with AF with an indication for anticoagulation include

Definite reasons to use a VKA – Clinical settings in which VKA (eg, warfarin; target INR 2.0 to 3.0; annual TTR ≥70 percent) is the agent of choice and in which DOAC should not be used

-Patients with rheumatic mitral stenosis that is severe or clinically significant (mitral valve area ≤1.5 cm2).

-Patients with mechanical heart valves of any type and any location.

-Patients with a (surgical or transcatheter) bioprosthetic valve implanted within the prior three to six months.

-Patients for whom the DOAC agents are avoided due to drug interactions (eg, those receiving P-glycoprotein drug efflux pump inducers, which can decrease the anticoagulant effect of DOACs) or antivirals that may increase the anticoagulant effect of DOACs.

Question 14

Diagnosis of PFO

Answer 14

Agitated saline contrast with ultrasound techniques (echocardiography or transcranial Doppler) enables shunt identification.
On agitated saline contrast echocardiography, appearance of at least three bubbles of contrast in the left heart within three beats after contrast opacification of the right atrium suggests the presence of intracardiac shunt.

• TTE – Among those with cryptogenic stroke or other clinical indication for evaluation for PFO, we suggest starting with transthoracic echocardiography (TTE), with transesophageal echocardiography (TEE) performed if TTE is negative or nondiagnostic.
• TEE – TEE with contrast at rest, with cough, and following Valsalva is generally considered the most definitive diagnostic test for PFO. TEE and transcranial Doppler methods have similar sensitivity and specificity for detection of right-to-left shunts, although echocardiography also permits evaluation of cardiac structure and function.

In summary, TEE with contrast at rest, with cough, and following Valsalva is generally considered the most definitive diagnostic test, although second harmonic TTE in patients with good acoustic windows may offer equal or greater sensitivity!

Question 15

Patient selection for PFO closure

Answer 15

patients with PFO who meet all of these criteria are candidates for percutaneous PFO closure:

• Age ≤60 years
• Embolic stroke topography
• No other evident source of stroke despite a comprehensive evaluation
• A possible, probable, or definite likelihood that the stroke was causally related to the PFO according to the PFO-associated stroke causal likelihood (PASCAL) classification system, which incorporates the Risk of Paradoxical Embolism (RoPE) score and high-risk features of the PFO on echocardiogram
• No concurrent indication for anticoagulation

Question 16

Approach to management of a patient with PFO and embolic-appearing ischemic stroke without other identified cause

Answer 16

https://www.uptodate.com/contents/image?imageKey=NEURO%2F138535&topicKey=NEURO%2F138296&search=pfo%20closure&rank=1~150&source=see_link

Question 17

Embolic stroke of undetermined source (ESUS) definition

Answer 17

The criteria for ESUS are:

● Stroke detected by CT or MRI that is not lacunar (lacunar is defined as a subcortical infarct in the distribution of the small, penetrating cerebral arteries whose largest dimension is ≤1.5 cm on CT or ≤2.0 cm on MRI diffusion images)

● Absence of extracranial or intracranial atherosclerosis causing ≥50 percent luminal stenosis of the artery supplying the area of ischemia

● No major-risk cardioembolic source of embolism (ie, no permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, recent (within four weeks) myocardial infarction, left ventricular ejection fraction <30 percent, valvular vegetations, or infective endocarditis)

● No other specific cause of stroke identified (eg, arteritis, dissection, migraine, vasospasm, drug abuse)

Question 18

Useful score to detect patients with stroke who are at high risk of having AF as a cause (and use prolonged heart monitoring)

Answer 18

1) HAVOC

2) C2HEST score (coronary artery disease or chronic obstructive pulmonary disease [1 point each]; hypertension [1 point]; elderly [age ≥75 years, 2 points]; systolic heart failure [2 points]; thyroid disease [hyperthyroidism, 1 point])

Question 19

Σε ποιους ασθενείς είναι καλύτερα να αποφεύγεται η χρήση εμφυτεύσιμου καταγραφέα

Answer 19

Ασθενείς <60 ετών χωρίς δομική καρδιακή ανωμαλία
(Χαμηλή πιθανότητα ανίχνευσης AF και υψηλό κόστος τοποθέτησης)

33ο Πανελλήνιο

Question 20

Πόσο πρέπει να διαρκεί η καταγραφή από εμφυτεύσιμο καταγραφέα?

Answer 20

Ιδανικά πάνω από 2 χρόνια

33ο Πανελλήνιο

Question 21

Mechanisms of embolic stroke of undetermined source (ESUS)

Answer 21

mechanisms of embolic stroke of undetermined source (ESUS) include:

● Cardiac embolism secondary to occult paroxysmal atrial fibrillation (AF), aortic atheromatous disease, or other cardiac sources (πχ low risk - ανεπάρκεια αριστερής κοιλίας ή ήπιες βαλβιδοπάθειες)

● Paradoxical embolism, which originates in the systemic venous circulation and enters the systemic arterial circulation through a patent foramen ovale (PFO), atrial septal defect, ventricular septal defect, or extracardiac communication such as a pulmonary arteriovenous malformation

● Undefined thrombophilia (ie, hypercoagulable states including those related to antiphospholipid antibodies or to occult cancer with hypercoagulability of malignancy)

● Substenotic cerebrovascular disease (ie, intracranial and extracranial atherosclerotic disease causing less than 50 percent stenosis) and other vasculopathies (eg, dissection) και αρτηριοαρτηριακή εμβολή!!

Question 22

ESUS secondary prevention

Answer 22

There is no proven benefit of anticoagulation compared with antiplatelet therapy for preventing recurrent ischemic stroke in patients with cryptogenic stroke, including those with embolic stroke of undetermined source (ESUS).

Question 23

Ποσοστό παροξυσμικής κολπικής μαρμαρυγής σε κρυπτογενές ΙΑΕΕ

Answer 23

Μόνο 30%!

Πιο αποτελεσματικός τρόπος ανίχνευσης με εμφυτεύσιμο καταγραφέα
Το ποσοστό αυξάνεται όσο μεγαλύτερος είναι ο χρόνος καταγραφής από εμφυτεύσιμη συσκευή
Το ποσοστό δεν φαίνεται να αυξάνεται εάν συνυπάρχει κολπκή καρδιοπάθεια

33ο Πανελλήνιο

Question 24

When to suspect infective endocarditis

Answer 24

Endocarditis should be suspected in any patient with unexplained fevers, night sweats, or signs of systemic illness
This is particularly true if the patient has any of the following risk factors: a prosthetic heart valve, structural or congenital heart disease, intravenous drug use, and a recent history of invasive procedures

Question 25

In which way can infections cause stroke

Answer 25

1) endocarditis and, secondarily cardioembolism

2) cerebral vasculitis
common conditions and organisms associated with infectious cerebral vasculitis include syphilis, Lyme disease, invasive fungi, and herpes zoster

Question 26

Non-infectious causes of vasculitis-associated stroke and clues for suspicion

Answer 26

• giant cell arteritis
• Takayasu disease
• eosinophilic granulomatosis with polyangiitis
• granulomatosis with polyangiitis
• polyarteritis nodosa
• Buerger disease

mononeuritis multiplex, visual loss, seizures, muscle disease, and encephalopathy

Question 27

What should be checked in patients with stroke and low ejection fraction

Answer 27

Prolonged cardiac rythm monitoring for AF detection

(Left ventricular systolic dysfunction is associated with AF)

Question 28

Left ventricular thrombus with or without stroke management

Answer 28

At least 3 months of anticoagulation with warfarin and until repeat cardiac imaging shows resolution of the thrombus

Question 29

Patients with heart failure with reduced ejection fraction (HFrEF) (LVEF ≤40 percent) in sinus rhythm and prior thromboembolic event who lack another cause of thromboembolism management

Answer 29

We suggest a vitamin K antagonist (eg, warfarin) versus no anticoagulant

Due to lack of data, we do not consider newer anticoagulants such as dabigatran or rivaroxaban alternatives to warfarin in this setting.

Uptodate

Question 30

Patients in sinus rhythm with LV systolic dysfunction (with or without HF) without coronary artery disease, prior thromboembolic event, acute LV thrombus, atrial fibrillation or other indication for antithrombotic therapy management

Answer 30

We recommend against administering aspirin or vitamin K antagonist

Uptodate

Question 31

Valvular pathologies that are associated with increased stroke risk

Answer 31

1) prosthetic heart valves
2) rheumatic heart disease
3) both infective and noninfective endocarditis

Question 32

Ischemic stroke in the setting of mechanical heart valve management

Answer 32

current guidelines recommend anticoagulation with warfarin with a goal INR of 2.5 to 3.5 for a mechanical aortic valve and a mechanical mitral valve

Question 33

Can DOACs be administered in patients with mechanical heart valves

Answer 33

No

Question 34

Patients with a bioprosthetic aortic or mitral valve, a history of ischemic stroke or TIA before valve replacement, and no other indication for anticoagulation therapy beyond 3 to 6 months from the valve placement: long-term therapy

Answer 34

aspirin is recommended in preference to long-term anticoagulation to reduce the risk of recurrent stroke or TIA.

Question 35

Ischemic stroke in patients with rheumatic mitral disease management

Answer 35

1) In patients with ischemic stroke and rheumatic mitral disease without atrial fibrillation, there is no evidence to support oral anticoagulation therapy.

2) In those with atrial fibrillation and moderate to severe mitral stenosis, warfarin is preferred

3) in those with atrial fibrillation but without moderate to severe mitral stenosis, direct oral anticoagulants or warfarin could be used

Question 36

How much time after myocardial infarction there is a high risk for stroke

Answer 36

first 12 weeks

Question 37

Major risk factors for noninfective endocarditis

Answer 37

1) systematic lupus erythematosus (Libman-Sacks endocarditis)
2) malignancy (marantic endocarditis)

Less common etiologies include inflammatory conditions such as antiphospholipid syndrome, rheumatoid arthritis, sepsis, and burns.

Question 38

Infarct patterns in infective and noninfective endocarditis

Answer 38

any infarct pattern can be seen with infective endocarditis, whereas disseminated punctate lesions are the dominant infarct pattern in noninfective endocarditis

Question 39

Treatment of endocarditis and stroke

Answer 39

1) For infective endocarditis, treatment entails IV antimicrobial treatment for at least 6 weeks as well as consideration for surgery in a subgroup of patients.
Surgery is typically considered in those with valvular dysfunction causing heart failure, complications (eg, paravalvular extension), or poor response to antimicrobial therapy. Antithrombotics are generally contraindicated in the acute setting

2) In patients with marantic endocarditis in the setting of cancer,
treatment entails treating the underlying malignancy as well as antithrombotic therapy.
In these patients, some experts suggest direct oral anticoagulants or parenteral anticoagulation with heparin or low-molecular-weight heparin and others only suggest parenteral anticoagulation with heparin or low-molecular weight heparin, but a high level of evidence supporting those treatments is lacking.

3) In patients with ischemic stroke in the setting of Libman-Sacks endocarditis, guidelines suggest anticoagulation with heparin or low-molecular weight heparin instead of oral anticoagulation if deemed safe, but these suggestions lack high levels of supporting evidence

Question 40

Which pathology is associated with chronic kidney disease

Answer 40

Cerebral microbleeds

Question 41

Patients with atrial flutter and stroke or TIA management

Answer 41

Anticoagulant therapy similar to that in AF is indicated to reduce the risk of recurrent stroke

Question 42

Patients with a mechanical mitral valve and a history of ischemic stroke or TIA before valve replacement management

Answer 42

Aspirin (75–100 mg/d) is recommended in addition to warfarin with an INR target of 3.0 (range, 2.5–3.5) to reduce the risk of thrombosis and recurrent stroke or TIA

Question 43

Patients with ischemic stroke or TIA and native aortic or nonrheumatic mitral valve disease (eg, mitral annular calcification or mitral valve prolapse) who do not have AF or another indication for anticoagulation management

Answer 43

Antiplatelet therapy is recommended to reduce the risk of recurrent stroke or TIA

Question 44

Patients with history of ischemic stroke or TIA and a mechanical aortic valve management

Answer 44

Anticoagulation with higher-intensity warfarin to achieve an INR of 3.0 (range, 2.5–3.5) or the addition of aspirin (75–100 mg/d) can be beneficial to reduce the risk of thromboembolic events

Question 45

Recommended antithrombotic regimen in patients with history of ischemic stroke or transient ischemic attack (TIA) and different valvular heart disease conditions

Answer 45

AHA/ ASA 2021

Question 46

What diagnostic test should be done In patients with stroke or TIA in the setting of acute MI

Answer 46

It is reasonable to perform advanced cardiac imaging (eg, contrasted echocardiogram or cardiac MRI) to assess for the presence of LV thrombus

Question 47

Anticoagulant therapy for patients with cardiomyopathy, ischemic stroke, or transient ischemic attack (TIA) in sinus rhythm

Answer 47

LVAD = left ventricular
assist device

Question 48

When to treat AF

Answer 48

Approach to deciding whether to prescribe anticoagulant therapy for patients with AF:(excluding those with rheumatic mitral stenosis that is severe or clinically significant [mitral valve area ≤1.5 cm2], a bioprosthetic valve [surgical or transcatheter] within the first three to six months after implantation, or a mechanical heart valve) is as follows

*For a CHA2DS2-VASc score ≥2 in males or ≥3 in females we recommend chronic OAC

*For a CHA2DS2-VASc score of 1 in males and 2 in females

-For patients with CHA2DS2-VASc score of 1 in males and 2 in females based on age 65 to 74 years, we recommend chronic OAC
Age 65 to 74 years is a stronger risk factor than the other factors conferring one CHA2DS2-VASc score point.

Question 49

Stroke secondary prevention

Answer 49

https://www.uptodate.com/contents/overview-of-secondary-prevention-of-ischemic-stroke?search=stroke%20secondary%20prevention&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

Question 50

Blood pressure goal in secondary prevention

Answer 50

<130/80

ESO 2022

Question 51

LDL goal in secondary prevention

Answer 51

<55mg/dL

Hellenic Atherosclerosis Society Guidelines for the Diagnosis and Treatment of Dyslipidemias - 2023

Question 52

High intensity statins

Answer 52

High-intensity statin therapy (≥50 percent LDL-C reduction) includes daily treatment with:

● Atorvastatin 40 to 80 mg

● Rosuvastatin 20 to 40 mg.

Question 53

Antithrombotic therapy according to cause of acute ischemic stroke

Answer 53

https://www.uptodate.com/contents/image?imageKey=NEURO%2F131701&topicKey=NEURO%2F1120&search=stroke%20secondary%20prevention&rank=2~150&source=see_link

Question 54

PCSK9 inhibitors dosing

Answer 54

Evolocumab: Η συνιστώμενη δόση του Repatha είναι είτε 140 mg κάθε δύο εβδομάδες είτε 420 mg μία φορά το μήνα υποδόρια
(και οι δύο δόσεις είναι κλινικά ισοδύναμες)

Alirocumab: Η συνήθης δόση έναρξης του alirocumab είναι 75 mg χορηγούμενα υποδορίως μία φορά κάθε 2 εβδομάδες.
Σε ασθενείς στους οποίους απαιτείται μεγαλύτερη μείωση της LDL-C (>60%), η θεραπεία μπορεί να ξεκινήσει με χορήγηση 150 mg μία φορά κάθε 2 εβδομάδες, ή 300 mg μία φορά κάθε 4 εβδομάδες (μηνιαίως), υποδορίως.

Question 55

Lipid lowering treatment in secondary prevention

Answer 55

• High-intensity statin therapy – For patients with atherosclerotic cardiovascular disease, including TIA or ischemic stroke, we treat with high-intensity statin therapy (eg, atorvastatin 80 mg/day), independent of the baseline LDL-C, to lower the LDL-C to <70 mg/dL (πλέον <55mg/Dl)
• Intolerance of high-intensity statin therapy – For patients who are intolerant of high-intensity statin therapy, the maximally tolerated dose of a statin therapy can be used.
• LDL-C above goal despite statin therapy – For patients whose LDL-C level remains ≥70 mg/dL despite maximally tolerated statin therapy, adding ezetimibe or a PCSK9 inhibitor is reasonable.
• Patients unable to tolerate statin therapy – For patients who are unable to tolerate any statin regimen, we treat with ezetimibe; we consider adding a PCSK9 inhibitor if LDL-C remains ≥70 mg/dL