1. Echocardiography in the Evaluation of Intracardiac Sources of Embolism
Airley E. Fish, MD
Imaging Conference
Wednesday May 13, 2009

2. Introduction Intracardiac sources of CVA TEE
Account for k of 500k strokes/year in U.S.
TEE
Search for source of cardiac emboli is the leading clinical indication for TEE
More cost effective than TTE
Superior to TTE for most cardiac sources of emboli
Exceptions
Assessment of LV systolic function
Identification of LV apical thrombi

3. Superiority of TEE vs TTE
Pearson et al 1991 in JACC
79 patients with cryptogenic stroke
TEE ID’ed source in 57%
TTE ID’ed source in only 15%
Rauh et al 1996 in Stroke
30 patients with CVA and low-risk for embolism
Sinus rhythm
No cardiac disease related to embolism
Minimal carotid artery stenosis
TTE showed no embolic sources
TEE showed
Aortic plaques in 19
PFO in 7
LAA thrombus in 3
Atrial septal aneurysm in 2

4. Major Sources of Emboli
Masses
LA/LV Thrombi
Atherosclerotic plaques
Vegetations
Tumors
Propensity for Thrombus Formation
LA spontaneous echo contrast
MAC
Passageways for Paradoxical Embolism
PFO/ASD

5. Major Cardioembolic Sources
Aortic Atherosclerotic Plaques
Atrial myxoma
LA Thrombus
-Atrial fibrillation
-Sustained atrial flutter
PFO/ASD
Rheumatic Mitral (MAC) or Aortic Valve Disease
LA Spontaneous
Echo Contrast
LV Thrombus
-Recent AMI
-EF < 30%
Mechanical or Bioprosthetic Valve
Vegetations
Tumors

6. Most Common Sources of Emboli
LA Thrombi
LA Spontaneous Echo Contrast
Aortic Atherosclerosis
LV Thrombi
Prosthetic Valve Thrombi
Abnormalities of the Interatrial Septum

7. LA Thrombi Account for 45% of cardiogenic thromboemboli
Manning et al 1995, Annals of Internal Medicine
Intraoperative visualization vs TEE LA/LAA
Sensitivity and specificity TEE 100%, 99%
TTE LA/LAA
Sensitivity and specificity TTE 39%, 65%
Most often associated with
Atrial fibrillation and/or
Rheumatic mitral stenosis

8. LA Thrombi – AF vs NSR Leung et al 1997, Am Journal of Cardiology
2894 patients underwent TEE for various indications
94/2894 patients with LA thrombus
83/94 in AF
Stoddard et al 1995, J American College of Cardiology
TEE looking for LA thrombus in patients with AF
Acute AF - 14% with thrombus
Chronic AF – 27% with thrombus
AF and clinical thrombus - 43% with thrombus (?up to 57% with migration)
Omran et al 2000, American Heart Journal
869 patients with embolic CVA or TIA
If NSR, no MV disease, and normal LA function
Only 1% with LA thrombus
Therefore, routine TEE in sub-population not recommended

9. LA Thrombi

10. LA Thrombi
FIGURE In a patient with untreated rheumatic heart disease, a very large LA thrombus (arrows) is seen. The RA is also severely dilated.

11. LAA Thrombi
FIGURE TEE image of the left atrial appendage (LAA) in a patient with rheumatic MS and a LAA thrombus. Irregular echo density mass filling the LAA (thin arrows). Boundary of the wall of the LAA is as noted by the heavier arrows.

12. LA Thrombi
FIGURE A, B: Thrombus straddling the interatrial septum through a PFO and extending into the LA (small arrows). Thrombus was highly mobile & likely originated in the lower extremities. Increased mobility of atrial septal tissue indicated by large arrow.

13. LA Thrombi

14. LA Spontaneous Echo Contrast (SEC)
“Smoke-like” echoes seen within LA during TEE
Most common TEE finding in work up of thrombus source
Especially if AF or LAE
May also be seen in NSR
26/1288 with SEC
3/26 with LA thrombus (LAE, decreased LAA emptying velocity)
2º RBC aggregation in low shear rate conditions
RBC aggregation mediated by plasma proteins
Particularly fibrinogen
Promote RBC rouleaux formation (via elimination of normal negative electrostatic forces of RBC’s aggregation)
Increased plasma fibrinogen levels
Hypercoagulable state – Mitral stenosis
>2/3 patients with MS have TEE e/o SEC
Atrial blood stasis
Increased LA levels of prothrombin 1 and 2 (procoagulants)
MR may spontaneous echo contrast frequency

15. LA Spontaneous Echo Contrast
FIGURE TEE in a patient with rheumatic MS, LAE, and marked stasis of the blood within the LA and LAA. In the real-time image, the stasis of the blood appears as a dense swirling cloud of “smoke'' filling the LA and LAA.

16. LA Spontaneous Echo Contrast
FIGURE Expanded view of the LAA in a patient with AF. No distinct thrombus but vague swirling smoke-like echoes suggesting stagnant blood in the body of the LAA.

17. LA Spontaneous Echo Contrast
FIGURE Small thrombus within the LAA

18. Aortic Atherosclerosis
TEE sensitive for visualization of aortic intima
CT/MRI experience limited, cannot characterize plaque mobility
Aortic atherosclerotic plaques source of
Thromboemboli (relatively common)
Unstable atherosclerotic plaque, superimposed thrombi embolize
Tend to be single, lodge in small or medium arteries
Often resulting in CVA/TIA
Can also result in limb and organ (kidney, GI, etc.) ischemia
Atheroemboli/Cholesterol Emboli (fairly rare)
Arterio-arterial embolism of small pieces of atheromatous material
Multiple small artery occlusions tissue/organ damage
Ischemic digits, retinal ischemia, intestinal infarction, etc.
Patients with
Unexplained CVA
TIA
Arterial embolization

19. Aortic Atherosclerosis: Thromboembolism

20. Aortic Atherosclerosis: Thromboembolism
Postmortem specimen of a terminal aorta with a thromboembolus from a cat with HCM and an acute onset of caudal limb pain and paresis. Thromboembolus lodged at the terminal aorta ("saddle" thromboembolus), with portions extending into the external iliac arteries

21. Aortic Atherosclerosis: Thromboembolism

22. Aortic Atherosclerosis: Thromboembolism
Thoracic aortic plaque/plaque mobility – TEE
Complex aortic plaque
> 4 mm thick (more likely to be lipid-laden)
Mobile
Ulcerated
Pedunculated

23. Aortic Atherosclerosis: Thromboembolism

24. Aortic Atherosclerosis: Thromboembolism
FIGURE Suprasternal notch TTE in a patient with atheromatous involvement of the proximal descending thoracic aorta. Notice the relatively normal aortic arch (Ao) and the distinct echo density protruding into the lumen of the proximal descending thoracic aorta that represents focal pedunculated atheroma.

25. Aortic Atherosclerosis: Thromboembolism
FIGURE 20.51A. TEE in short-axis view of the descending thoracic aorta. Note the relatively circular aorta into which there is marked protrusion by pedunculated atheroma

26. Aortic Atherosclerosis: Thromboembolism
FIGURE TEE recorded in the longitudinal plane of a descending thoracic aorta with aneurysm. The arrows outline the external boundary of the aorta with all space in between representing an aneurysm with complex atheroma. Note the markedly complex atheroma with multiple pedunculated and mobile components filling the dilated lumen.

27. Aortic Atherosclerosis: Thromboembolism
Treat for 2º prevention of CVD if
Complex aortic plaque (regardless of CVA/peripheral embolism)
or Simple aortic plaque and unexplained CVA/peripheral embolism
2º Prevention of CVD
Aspirin (or other antiplatelet agents) – ARCH trial underway in Europe
If CVA and plaque > 4 mm and/or mobile
?Warfarin with goal INR statin
?Aspirin 325 mg PO q day + statin
If no CVA and plaque mobile
If no CVA and plaque > 4 mm
Statins (recommend same goal as for known CAD, no RCT’s to date)
Blood pressure control
Smoking cessation
If diabetic, glycemic control

28. Aortic Atherosclerosis: Thromboembolism
Possible benefit of aortic arch replacement
Prophylactic atherectomy ? ‘ed CVA risk
Undergoing cardiac surgery consider
Intraoperative U/S to guide aortic manipulation sites
Use of off-pump CABG may be beneficial
Cross-clamping & performance of proximal anastamosis may risk of embolization 2º mechanical disruption

29. Aortic Atherosclerosis: Cholesterol Emboli

30. Aortic Atherosclerosis: Cholesterol Emboli

31. Aortic Atherosclerosis: Cholesterol Emboli
Light micrograph of an atheroembolus in a muscular renal artery showing cleft-like spaces (arrow) due to washout of the cholesterol crystals during histologic processing

32. Aortic Atherosclerosis: Cholesterol Emboli
TEE descending thoracic aorta
Massive atherosclerotic plaque
Images on the right (1A, 2A, 3A) taken 1-2 seconds after their respective pictures on the left
Arrows point to small particles of embolic material moving in
transit in the aortic lumen
Patient died from
Intestinal infarction
Renal failure

33. Aortic Atherosclerosis: Cholesterol Emboli
Risk factors for atheroembolic disease
Age
Smoking
Hypercholesterolemia
Hypertension
Agmon et al 2000, in Circulation
Population-based study of those with aortic plaque
Odds of complex plaque increased as ambulatory SBP increased
OR 1.43 for each 10 mmHg increase
Obesity
Diabetes
CRP

34. Aortic Atherosclerosis: Cholesterol Emboli
Often blamed on Rx with anticoagulant drugs
?plaque hemorrhage as precipitant
Tunick et al 2002, in Am J Cardiology
519 with severe aortic plaque
Cholesterol emboli in only 5/519 over > 3 years
No difference between anticoagulation and events
2/206 on warfarin
3/313 off warfarin

35. Aortic Atherosclerosis: Cholesterol Emboli
2º Prevention of CVD
Aspirin (or other antiplatelet agents)
Statins (same goal as for 2º CAD, no RCT’s to date)
?Lower LDL
?Pleotrophic effects of plaque stabilization
In above retrospective trial of 519 patients, statins associated with a significantly lower rate of recurrent CVA & thromboembolism
Blood pressure control
Smoking cessation
If diabetic, glycemic control

36. LV Thrombi – Background & Incidence
Among most common complications of STEMI
Dependent upon infarct location and size
Large, anterior STEMI’s
Aneurysm formation and akinesis or dyskinesis
Reduced LVEF
Increased WMA’s
Develop early (within 2 weeks, median 5 days), embolization within 1st 4 months
Incidence in reperfusion era – (predominantly thrombolytic therapy)
8326 patients GISSI-3 database
LV thrombus 5.1%, overall
Anterior infarct 11.5% with LV thrombus
Other infarcts 2.3% with LV thrombus
May be underestimate (excluded severe CHF and SBP < 100 mmHg)
Incidence in reperfusion era – (primary PCI)
163 patients
LV thrombus 4.3%, overall
Anterior infarct 10.4% with LV thrombus
Other infarcts 0% with LV thrombus

37. LV Thrombi – Incidence and Risk Factors
In reperfusion era (incidence decreasing)
LV aneurysm 8-15% of Q wave infarctions
Mural thrombus ID’ed in >50% of these cases
Two factors contribute to clot formation
Stasis of flow in aneurysm cavity
Contact of blood with fibrous tissue in aneurysm (rather than normal endocardium)

38. LV Thrombi - Diagnosis
TTE is a Class I indication for assessment of mural thrombus after acute STEMI
Presence of thrombus
Risk factors for embolization

39. LV Thrombi - Appearance
Thrombus appearance
Very fresh/red
Protrude into cavity center
Highly mobile
Difficult to differentiate from effect of slowly moving cavitary blood seen within LV aneurysms (highly reflective, luminescent)
Older
Smooth cavitary surface (resemble liver tissue)
Less likely to change or embolize

40. LV Thrombi – Risk for Embolization
High risk for embolization
Mobile thrombi
Embolization in 26/119 with LV thrombus s/p STEMI
Free mobility in 58% of patients with embolization
15/18 patients with free mobility (83% vs 11%) embolized
Free mobility in 3% of patients without embolization
Protruding thrombi (into LV cavity)
Protrusion in 88% of patients with emboli
23/40 patients with protruding thrombi embolized (58% vs 4%)
Protrusion in 18% of patients without emboli

41. LV Thrombi - Prevention
ACE-I thought to result in fewer LV thrombi via preservation of LVEF and wall motion
No difference in patients on/off lisinopril in GISSI-3
Short-term (10 days)
Unfractionated Heparin vs Heparin SQ
Out of 221 patients, LV thrombus in 11% vs 32%
2004 ACC/AHA STEMI guidelines
Warfarin reasonable with severe LV dysfxn/WMA’s for the prevention of LV thrombus formation

42. LV Thrombi – Embolization Prevention
No RCT’s
Warfarin reduces risk of embolization
May prevent thrombus extension
May prevent thrombus endothelialization
May not promote thrombus resolution
2004 ACC/AHA STEMI guidelines - LV thrombus
Warfarin 3-6 months
Indefinitely, if no increased risk of bleeding
2006 AHA/ASA – prevention of ischemic CVA
Warfarin 3 months – 1 year
Goal INR 2-3
Also recommend concurrent ASA Rx for 2º prevention
Consider increased risk of bleeding in PCI (triple Rx)

43. LV Thrombi
FIGURE Apical view in a patient with a vague echo density on noncontrast imaging. After IV injection of a perfluorocarbon-based agent, a distinct spherical filling defect is noted in the apex, consistent with a pedunculated apical thrombus

44. LV Thrombi
FIGURE Apical four-chamber view recorded in a patient with an acute anterior apical MI and early thrombus formation. Note the regional dilation of the LV at the apex and the pedunculated, multilobulated mass protruding into the cavity of the LV.

45. LV Thrombi
FIGURE Apical four-chamber view recorded in a patient with an acute anteroapical MI and a pedunculated, slightly mobile apical thrombus

46. LV Thrombi
FIGURE Apical two-chamber view recorded in a patient with an anteroapical MI & multiple large pedunculated & mobile thrombi. Note multiple masses protruding into the cavity of the LV apex & the mobile nature of these thrombi in the real-time image.

47. Prosthetic Valve Thrombi
Common in patients with mechanical valves
Especially if mitral/tricuspid valves (“low-flow”)
Especially if suboptimal anticoagulation
Goal INR
Best evaluated by TEE
Although often assumed clinically
No other obvious cause
Sub-therapeutic INR
Confirmatory, but doesn’t change Rx
Unless valvular dysfunction 2º to a massive thrombus

48. Prosthetic Valve Thrombus – Aorta
FIGURE 14.39A. Even a small thrombus, if properly located, can result in obstruction. A: A St. Jude aortic prosthesis is shown. A thrombus was not visualized. B: Color Doppler imaging demonstrates increased turbulence and significant aortic regurgitation (arrow). C: From the transthoracic study, a peak pressure gradient of 95 mm Hg confirms the presence of significant obstruction.

49. Prosthetic Valve Thrombus – Mitral
FIGURE 14.37A. In this example, a large thrombus was visualized on transthoracic (A) imaging. The thrombus can be seen on the LA aspect of the mitral prosthesis.

50. Abnormalities of the Interatrial Septum
Thromboemboli via 2 mechanisms
R L shunting via PFO/ASD
Interatrial septal aneurysm

51. PFO/ASD Echocardiography with contrast (IV saline)
Rest
Cough
Valsalva
Alternatively, transmitral Doppler with contrast

52. PFO
FIGURE Contrast injection demonstrates a PFO on TEE. In this case, increased mobility of the atrial septum is present. The tunnel-like gap within the interatrial septum is evident, and bubbles can be seen traversing the PFO from right to left.

53. PFO
FIGURE A TEE of the interatrial septum demonstrates a small PFO using color Doppler imaging.

54. PFO
FIGURE 21.42A. A large, tubular-shaped thrombus demonstrated as it crosses a PFO. The shape of the thrombus suggests that it was formed within the veins of the lower extremities. Its presence within the left heart greatly increases the likelihood of systemic embolization.

55. ASD
FIGURE Contrast echocardiography can be used to demonstrate intracardiac shunting through an ASD. In this example, sequential images after IV contrast injection demonstrate the appearance of bubbles in the right heart.

56. ASD
FIGURE 18.52A&B. A secundum ASD is detected during TEE. A: The location and size of the defect are evident. B: Color Doppler imaging reveals flow predominantly from the LA to the RA

57. ASD
FIGURE TEE recorded after placement of an atrial septal closure device. IV contrast has been injected to confirm the lack of persistent shunting.

58. Atrial Septal Aneurysm (ASA)
Congenital malformation
2º redundant atrial septal tissue
Typically involving the region of the fossa ovalis
Prevalence 0.5% via TTE, up to 5% via TEE
Embolic events via
Associated PFO
Direct thrombus formation in the aneurysm’s neck

59. Atrial Septal Aneurysm (ASA)
FIGURE 21.53A. An example of an atrial septal aneurysm is shown. A: The aneurysm billows into the LA. B: The redundant tissue billows into the RA. Injection of contrast into the right heart confirms an associated PFO by demonstrating right-to-left shunting.

60. Atrial Septal Aneurysm (ASA)
FIGURE A: An apical four-chamber view demonstrates an extreme form of an atrial septal aneurysm with a “windsock'' appearance of the aneurysmal tissue into the right atrium and partially through the tricuspid valve.

61. Atrial Septal Aneurysm (ASA)
FIGURE B: After contrast agent injection, the windsock is outlined by the contrast that flows around it from the RA to the RV. In addition, the presence of a PFO allows some contrast agent to cross into the left heart.

62. Atrial Septal Aneurysm (ASA)
Retrospective studies in patients with CVA
Approximately 10% with atrial septal aneurysm
Prospective trial in ASA suggests CVA risk low
846 patients undergoing TEE during cardiac surgery
4.9% with incidental finding of ASA
56% with a patent aneurysm
67% of those with a patent aneurysm rx’ed with aspirin
No CVA’s or systemic embolization in 70 months

63. PFO/ASD Conflicting Data
Association between paradoxical emboli & cryptogenic CVA well established in patients < 55, less so if > 55
Meta-analysis of case control studies
PFO (OR 3.1 <55, OR 1.3 >55)
ASD (OR 6.1 <55, OR 3.4 >55)
Both (OR 15.6 <55, OR 5.1 >55)
Population-based studies
No statistically significant association between risk of 1st CVA & presence of a PFO
Prospective studies
Presence of a PFO alone is NOT associated with an risk of recurrent CVA in patients with cryptogenic stroke
PFO + Interatrial septal aneurysm may CVA risk

64. PFO/ASD Rx for 2º Prevention of CVA
No RCT’s completed
Insufficient evidence for surgical/percutaneous vs medical management
Risk reduction strategies
HTN, hyperlipidemia (statins), antiplatelet Rx
General measures
Avoid Valsalva (transient R-L shunting)
Prevention of DVT (body positions that provoke)

65. PFO/ASD Rx for 2º Prevention of CVA
Isolated PFO (? in recurrent CVA)
Antiplatelet agent (Aspirin 81 vs 325, no dose RCT’s)
Percutaneous closure of PFO in recurrent cryptogenic CVA despite warfarin approved in 2001 under HDE, but > 4000 patients would have qualified so approval withdrawn in 2006
PFO+ASA (? in recurrent CVA < 55, Ø death)
Conflicting data for antiplatelet/warfarin (? Ø difference)
Warfarin if felt to be at high risk for recurrence or if DVT
Isolated ASA (10 pts in French study on ASA, no repeat CVA)
Warfarin if CVA associated with DVT
Consider surgical excision if recurrence on antiplatelet/anticoagulation