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Thrombosis in Atrial Fibrillation Chapter | 23 345
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TABLE 23.2 Risk Scores for Stroke and Combined Embolic Events
Risk Scores for Nonvalvular Atrial Fibrillation Based on
CHA
Score Stroke Risk (% per year) CVA/TIA/Embolism (%)
0 0.2 0.3
1 0.6 0.9
2 2.2 2.9
3 3.2 4.6
4 4.8 6.7
5 7.2 10
6 9.7 13.6
7 11.2 15.7
8 10.8 15.2
9 12.2% 17.4
CVA, cerebrovascular accident; TIA, transient ischemic attack.
Based on the Swedish Atrial Fibrillation Cohort Study (Ref: Friberg L, Rosenqvist M, Lip
GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in
182,678 patients with atrial fibrillation: the Swedish atrial fibrillation cohort study. Eur
Heart J June 2012;33(12):1500e10.).
-VASc Scheme
2DS2
The CHA2DS2-VASc has overtaken the CHADS2on the criticism that CHADS2omitted important risk factors such as
intermediate age (65e75 years), vascular disease, and gender, as well as categorizing too many patients as intermediate
risk, which essentially left the choice of anticoagulation to the discretion of the physician. With that said, a comparison of
nine different schemes to predict thromboembolism found no profound difference in the accuracy of risk prediction with
regard to those at high risk for thromboembolism [62a]. The C statistic, a statistical measure of goodness of fit, ranged
between 0.56 and 0.68 among all schemes in the high-risk category. Identification of low-risk patients, those who may not
need OAC, seemed best predicted by the CHA
-VASc scheme [62a,b].
2DS2
A newer stroke risk score scheme is the ATRIA, which includes a history of cerebrovascular accident, age broken into
four segments (<65, 65e74, 74e84, >85 years), gender, diabetes, CHF, HTN, proteinuria, and glomerular filtration rate
(GFR) <45. Of note, a history of prior stroke amplifies the point score in each of the age categories. In a large retrospective
study of 60,594 patients with AF, risk of stroke in un-anticoagulated patients was assessed by ATRIA, CHADS
CHA
-VASc score [63]. The ATRIA scheme modestly improved risk discrimination over the other two schemes,
2DS2
, and
2
mainly by identifying a larger number of low-risk patients who may not require OAC. Its use, based on current guidelines,
is adjunctive to the more established CHA
-VASc scheme.
2DS2
IMAGING OF THROMBOSIS IN ATRIAL FIBRILLATION
Two-dimensional echocardiography is a common modality for assessing the cardiac structure. Because of the posterior
anatomical location of the LAA, the sensitivity and specificity of transthoracic echocardiography for detecting LA
thrombus are relatively low (39%e63%) [64,65]. The gold standard for LA thrombus detection has been TEE. Sensitivity
and specificity have been assessed by surgical visualization. In a prospective cohort study, 231 consecutive patients undergoing TEE before elective repair/replacement of the mitral valve or excision of the LA tumor were studied [66]. In this
study, 56% of the patients had a history of AF and 17% had a history of thromboembolism. TEE identified 14 LA thrombi
in 14 patients (6% of patients studied). Thrombus size ranged from 3 to 80 mm. Surgery confirmed 12 or 14 thrombi, or
86%, and no additional thrombi were identified by direct visual means. This resulted in a sensitivity of 100% (95% CI
74%e100%) and a specificity of 99% (95% CI 97%e99.9%). More importantly to decision-making in the individual
patient, the positive predictive value was 86% and negative predictive value 100%. In a second prospective trial in patients
undergoing mitral valve operations for rheumatic heart disease (n ¼ 213), TEE performed within 3 days of surgery had
similar detection characteristics. In this study the posit ive predictive value was 100% and the negative predictive value
98.9% [67].
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With AF ablation becoming more readily available, imaging modalities, used to help perform this procedure, have been
evaluated for detection of LA thrombi. These include both cardiac computed tomography and CMRI. In a meta-analysis of
cardiac computed tomography, 19 studies involving 2955 patients were reviewed [68]. Most utilized a 64-slice multidetector computed tomography with electrocardiographic gating. This was compared directly with TEE. The incidence of
thrombi detection was 8.9%. When delayed images were utilized, the sensitivity and specificity were 100% and 99%,
respectively. This correlated to a positive predictive value of 92% and negative predictive value of 100%. The authors of
this meta-analysis concluded that cardiac computed tomography using delayed imaging is a reliable alternative to TEE for
the detection of LA thrombi.
Multicomponent CMR I for assessment of LA thrombi has also been assessed [69]. Patients with AF who were
scheduled for PVI ablation were studied (n ¼ 261 with average CHADS
-VASc ¼ 2). Patients underwent multicomponent
2
CMRI for evaluation of pulmonary venous anatomy before PVI and had TEE within 7 days. LA and LAA thrombi were
evaluated by using CMRI as follows: (1) cine-CMRI, (2) contrast-enhanced magnetic resonance angiography, and (3)
equilibrium-phase DE-CMRI with a long inversion time (TI) of 600 ms (long-TI DE-CMRI). Components of the CMRI
study were evaluated for detection of LA or LAA thrombus using TEE as the reference standard. CMRI and TEE were
performed within 1.3 2.3 days. LA/LAA thrombi were discovered in nine patients (3.5%) by using TEE. Among the
CMRI techniques performed, long-TI DE-CMRI had the highest diagnostic accuracy (99.2%), sensitivity (100%), and
specificity (99.2%). The authors conclu ded that in patients referred for PVI, CMRI could be a single complete diagnostic
study for assessment of both pulmonary vein anatomy and presence of LA thrombi, thus reducing the number of
preoperative tests before PVI.
PHARMACOLOGICAL TREATMENT OF THROMBUS FORMATION IN ATRIAL
FIBRILLATION
The most imperative aspect in treating patients with AF is prevention or reduction of stroke risk. Beyond this issu e, AF is
treated in large part based on clinical symptom s and rate control. Dating back to the 1980s, there are numerous treatment
trials looking at antiplatelet therapy (APT) in nonvalvular AF. In a meta-analysis of 10 trials looking at aspirin versus
placebo, dipyridamole plus aspirin versus placebo, as well as aspirin plus low-dose warfarin versus control, the effectiveness of APT for prevention of stroke in nonvalvular AF was evaluated [70]. In these trials, APT dosage ranged between
50 and 1300 mg per day. APT overall had a 22% reduction in stroke versus control (95% CI 6%e35%). However, within
the individual APT trials, aspirin benefit varied greatly. Most importantly, it was found that compared with placebo the
relative benefit of APT for preventing stroke in patients with AF significantly decreased with age, with minimal benefits for
those greater than 75 years of age [71].
In higher risk pati ents, with CHA
-VASc score of 2 or great er (correlating to annual risk of stroke/TIA/embolism
2DS2
>2.9%), OAC has fared well in reducing stroke risk. Warfarin is a vitamin K antagonist that exert s its anticoagulant effect
by inhibiting the clotting factors II, VII, IX, and X. Warfarin’s therapeutic window is fairly small, achieving the greatest
beneficial effect with a prothrombin time and international normalized ratio (PT/INR) between 2 and 3. In fact, INRs less
than 1.7 carry a twofold risk of stroke. In a meta-analysis reviewing anticoagulation with warfarin versus control, the
combined end point of stroke, embolism, or TIA was reduced by 64% with anticoagulant use (95% CI, 49%e74%) [70].
When comparing adjusted-dose warfarin (PT/INR 2e3) versus APT, warfarin treatment had a 39% relative risk reduction.
Until recently warfarin therapy with INR between 2 and 3 has been the standard of care for nonvalvular AF in patients with
CHA
2DS2
-VASc >1.
In recent years the advent of a new pharmacological treatment has taken place with direct oral anticoagulant (DOAC)
therapies. One of the main difficulties with warfarin is maintaining proper therapeutic range. In the national assessment of
warfarin anticoagulation therapy for stroke prevention in AF, time in therapeutic range in patients on treatment for less than
6 monthswas 47.6% and only 57.5% in those who had been on therapyfor greater than 6 months [72].The distinct advantageof
DOAC therapy is that the drug effect is predictable and does not require constant adjustment and monitoring. As a class, the
potential benefits of DOACs versus warfarin are significant: DOAC onset of action is rapid versus relatively slow with vitamin
K antagonist; dosing is fixed; there are no food interactions; and half-life is relatively short. One of the major concerns with
DOACs, however, has been that there is no antidote to reverse anticoagulation. In October 2015, however, the US FDA
approved the first reversing agent for dabigatran, idarucizumab (Praxbind). Other reversing agents are sure to follow.
As of this writing there are four US FDA-approved DOACs. These include dabigatran, apixaban, rivaroxaban, and
edoxaban. Dabigatran is a direct thrombin inhibitor. Thrombin enables the conversion of fibrinogen into fibrin during the
coagulation cascade. Its inhibition prevents the development of a thrombus. Dabigatran and its active metabolites inhibit
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both free and clot-bound thrombin as well as thrombin-induced platelet aggregation. In its pivotal trial, the RELY trial,
dabigatran at either 110 or 150 mg twice daily was compared with standardized warfarin (INR 2e3) [73]. Patients
(n ¼ 18,113) were randomly assigned in a blind fashion with medium follow-up of 2 years. This was a noninferiority trial.
The primary outcome was stroke or systemic embolism. The primary outcome was reached at 1.69% per year in the
warfarin group compared with 1.53% and 1.11% in the dabigatran groups taking 110 and 150 mg, respectively. The rate of
major bleeding was 3.36% per year in the warfarin group, compared with 2.71% per year in the group receiving
110 mg (P ¼ .003) and 3.11% in 150 mg group (P ¼ .31). Hemorrhagic stroke was 0.38% per year in the warfarin group
compared with 0.12% and 0.10% in the 110 and 150 mg of dabigatran groups, respectively (P < .001). At this writing,
dabigatran has the distinction of having the only US FDA-approved reversing agent. As noted, in October 2015 the US
FDA approved idarucizumab, a monoclonal antibody designed as a reversal agent of dabigatran.
Apixaban is another DOAC but works via a different mechanism compared with dabigatran. Apixaban is an oral direct
factor Xa inhibitor. Factor Xa catalyzes the conversion of prothrombin to thrombin, the final enzyme in the coagulation
cascade that is responsible for fibrin clot formation. Apixaban functions as a direct inhibitor of both free and clot-bound
Xa. In the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation),
apixaban was compared with warfarin (INR 2e3) in 18,201 patients with nonvalvular AF [74]. The median follow-up was
1.8 years. The primary outcome was stroke (ischemic or hemorrhagic) or systemic embolism. Once again this was a
noninferiority trial. The rate of primary outcome was 1.27% per year in the apixaban group compared with 1.60% in the
warfarin group (P < .001 for noninferiority and P ¼ .01 for superiority). The rate of major bleeding was 2.13% per year in
the apixaban group compared with 3.09% in the warfarin group (P < .001). Hemorrhagic stroke was 0.24% per year in the
apixaban group compared with 0.47% per year in the warfarin group (P < .001). The rates of death from any cause were
3.52% and 3.94% in the apixaban versus warfarin treatment groups, respectively (P ¼ .047). The conclusions by the
authors of the ARISTOTLE trial were that apixaban was superior to warfarin in preventing stroke or systemic embolism
and caused less bleeding with a lower overall mortality. One advantage of apixaban is that a significantly lower percentage
of the drug is cleared through the kidneys. Thus sensitivity to changing GFR is less compared with other DOACS.
Apixaban has no dose adjustment recommendations for patients with renal impairment alone, including those with endstage renal disease maintained on hemodialysis. As of this writing, dose reduction (2.5 mg
patients with at least two of the following: age 80 years, body weight 60 kg, and serum creatinine 1.5 mg/dL.
Rivaroxaban, another oral factor Xa inhibitor, was evaluated in 14,264 patients with nonvalvular AF [75]. Again this
was in the comparison with dose-adjusted warfarin on a noninf eriority basis. The primary end point was stroke or systemic
embolism. In the analysis, the end point was reached in 1.7% per year in the rivaroxaban group versus 2.2% in the warfarin
group (P < .001 for noninferiority, P ¼ .12 for superiority). Major and nonmajor clinically relevant bleeding occurred in
14.9% of the rivaroxaban group and 14.5% in the warfarin group (P ¼ .44). Intracranial hemorrhage was significantly
reduced in the rivaroxaban group versus warfarin group (0.5% and 0.7%, respectively, P ¼ .02). In summary, rivaroxaban
was noninferior to warfarin for prevention of stroke or systemic embolism, with no significant difference in the risk of
overall major bleeding, although intracranial and fatal bleeding occurred less in the rivaroxaban group.
The most recent DOAC is edoxaban, also an oral factor Xa inhibitor. In the ENGAGE AF-TIMI 48 trial, 21,105
patients with moderate-to-high risk of AF had a medium follow-up of 2.8 years [76]. The primary efficacy end point was
stroke or systemic embolism. Test groups included once-daily 30 and 60 mg edoxaban versus warfarin (INR 2e3) in a
noninferiority study. The principal safety end point was major bleeding. The primary end point was 1.18% with high-dose
edoxaban (P < .001 for noninferiority), 1.61% for 30-mg dosing (P ¼ .005 for noninferiority), and 1.5% for warfarin.
Annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (P < .001) and 1.61%
with low-dose edoxaban (P < .001). Both once-daily regimens of edoxaban were noninferior to warfarin with respect to
prevention of stroke and systemic embolization, with lower rates of bleeding.
In a recent meta-analysis of all phase II and III clinical trials of DOACs versus warfarin for stroke prevention in patients
with nonvalvular AF, it was concluded that DOACs are a safe and effective alternative to warfarin in patients with at least a
CHA
overall mortality benefit (14% reduction) in favor of DOACs versus warfarin [77].
-VASc score ¼ 1. In addition, there appears to be a reduced number of hemorrhagic strokes, which leads to an
2DS2
po bid) is recommended for
MECHANICAL TREATMENTS FOR THE PREVENTION OF ATRIAL THROMBOSIS
FORMATION
Despite conclusive studies showing the benefits of OAC for prevention of stroke in the setting of AF, OAC use is estimated
to be significantly underutilized. In a systematic review of 98 studies concerning stroke prevention in AF, significant
348 Cardiovascular Thrombus
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undertreatment was found [78]. In patients who had a prior stroke treatment levels were below 60% (range 19%e81.3%).
Of patients with a CHADS
score of 2, treatment levels were below 70% (39%e92.3%). Explanations for the under-
2
utilization of OAC are vast, including bleeding risk, medical noncompliance, fall risk, and patient preference. As such,
attempts to find a nonpharmacological treatment of LA thrombosis have been significant.
Although it would be appealing to discontinue OAC after successful ablation AF, current guidelines recommend
continued use of OAC after AF ablation based on the patient’s preablation CHA
-VASc score [79]. It is hoped that
2DS2
ongoing studies looking at the benefits of AF ablation and stroke prevention will give us a more definitive answer on
continued use of OAC after successful ablation in the near future. Other mechanical options for treating LA thrombus
formation and AF have focused on the appendage.
LAA occlusion, as embolic protection treatment for patients with nonvalvular AF, is based on the high percentage of
where atrial emboli form. In a review of 23 studies involving patients with nonvalvular AF, the location of the atrial
thrombus was evaluated. Atrial thrombus location was evaluated by TEE, surgical observation, or autopsy [23]. Findings
showed 222 thrombi (17%) identified in 1288 patients. Greater than 91% of thrombi were located in the LAA (201 of 222).
This is contrasted by patients with valvular heart disease, in which only 57% of thrombi were located within the
appendage. Thus, if 90% of thrombus formation in nonvalvular AF occurs within the appendage, then occluding or
removing this structure may reduce stroke rates.
LAA removal during coronary artery bypass surgery is commonly performed but rarely as a stand-alone procedu re.
Given the significant number of patients with AF that may have contraindications to anticoagul ation long term, several
companies have developed mechanical devices for occlusion of the LAA that can be done in a percutaneous fashion. At the
time of writing there are three devices for LAA closure. Two devices occlude the appendage ori fice (WATCHMAN,
AMPLATZER Amulet). These are placed via a percutaneous and transseptal approach. The third is an extravascular snare
(Lariat) used to occlude the LAA via an external pericardial approach whereby access is gained percutaneously.
The WATCHMAN device (Boston Scientific) is a percutaneous occlusion device delivered via a transseptal approach
to the orifice of the LAA (Figs. 23.6 and 23.7). This LAA closure device is the most studied system. The WATCHMAN
device for embolic protection in patients with AF was compared with warfarin in a noninferiority study [80,81]. The
PROTECT AF trial included 707 patients with nonvalvular AF randomly assigned in a 2:1 ratio to either percutaneous
LAA occlusion with the WATCHMAN device or to warfarin therapy. The average CHADS
score was 1. Over an
2
average 3.8 years of follow-up, the LA closure device met the criteria for noninferio rity for the combined end point of
stroke, systemic embolism, and cardiovascular death. Because of early safety concerns of the trial (embolization, fracture,
and tamponade) and a high number of patients with CHADS
-VASc ¼ 1, the US FDA required a follow-up trial design to
2
look at safety issues [82]. The PREVAIL trial enrolled 407 patients randomized to LA occlusion (n ¼ 269) versus ongoing
warfarin therapy (n ¼ 138). In this study, the average CHA
-VASc score was 3.8 and 3.9 in the treatment and control
2DS2
groups, respectively. The PREVAIL study showed WATCHMAN to be noninferior to warfarin therapy in prevention of
ischemic stroke or systemic embolism >7 days postprocedure. Noninferiority to warfarin was not obtained, however, for
overall efficacy (composite of stroke, systemic embolism, and cardiovascular\unexplained death). Although noninferiority
was not achieved for overall efficacy, the author notes that event rates were low and numerically comparable in both arms.
Procedural safety also significantly improved, suggesting a learning curve to successful and safe deployment of the device.
FIGURE 23.6 Depiction of WATCHMAN (Boston Scientific,
Natick, MA. USA) closure device being delivered into the left-atrial
appendage via transseptal puncture. Reprinted with permission.
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FIGURE 23.7 Transesophageal echo image depicting Watchman
closure positioned into left atrial appendage. Reprinted with
permission.
Another endovascular device utilized for LAA closure is the AMPLATZER device (Fig. 23.8). Most data regarding this
system are based on registry data. A recently published meta-analysis was performed on 1047 patients from 22 centers
[83]. Procedur al success was labeled as 97.3% with a 4.9% periprocedural adverse event rate. Follow-up was on average
13 months. In the follow-up there were 0.9% strokes and 0.9% TIAs. This resulted in a 2.3% annual thromboembolic event
FIGURE 23.8 Depiction of AMPLATZER
Amulet (St. Jude Medical, St Paul, MN,
USA) placement into left atrial appendage
via the transseptal approach. Reprinted with
permission.
⊗
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rate. The authors concluded, based on historical controls, that this resulted in a 59% risk reduction. In addition, a similar
reduction in major bleeding was estimated (61%) . The device is receiving ongoing modification (AMPLATZER Amulet)
and further studies will be required to assess its long-term efficacy. At this writing, the most recent rendition of the Amulet
is being studied head-to-head with the WATCHMAN device, with trial results expected in the next couple of years.
Extravascular closure of the LAA using a snare is another closure approach. One such device, which uses a pericardial
approach, is the Lariat device (Figs. 23.9 and 23.10). The Lariat suture delivery device, manufactured by SentreHEART, is
a surgical tool cleared by the US FDA to deliver a pretied stitch (suture) to aid in soft tissue appendage closure. It is
introduced via the pericardial space under fluoroscopic and TEE imaging. Its placement is aided by an endocardial
magnetic tipped pericardial guide (FindrWirz) in the LAA with a second epicardial magnetic wire placed at the epicardial
surface of the distal appendage. The epicardial wire is deployed through a soft-tip epicardial sheath. The magnets are
connected, thus outlining the appendage. The lasso wire is then placed over the appendage and tightened. The largest
multicenter experience published on this approach comprised 712 patients [84]. Acute success was 95.5%. Of note, 30
procedures were aborted because of difficulty in obtaining pericardial axis or early complication. There was one death, 10
surgical repairs for cardiac perforation, and 14 effusions that required drainage. Randomized controlled trials are lacking
and further data are being developed at the time of this writing. In addition, there is significant interest in combining LAA
occlusion with pulmonary vein ablation with assessment of stroke reduction (AMAZE Trial: LAA Ligation Adjunctive to
PVI for Persistent or Longstanding Persistent Atrial Fibrillation). This study is a prospective multicenter randomized trial
that is currently enrolling.
Left atrium
EndoCATH Large
Occlusion Balloon
⊗
Left auricle
1
2
Magnetic guides
3
4
Left auricle
sutured off
Left auricle
atrophied
LARIAT
FIGURE 23.9 Lariat (SentreHEART, Redwood City, CA, USA) illustration depicting guiding catheters inside and outside the heart. The internal
catheter is delivered through the femoral vein and into the left atrium via transseptal puncture. The external guide is delivered through the pericardium.
Reprinted with permission.
Internal guide wire
External guide wire
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(A) (B)
FIGURE 23.10 (A and B) Fluorograms showing left atrial appendage snared (Lariat) proximal to the balloon. Reprinted with permission.
SUMMARY
Thrombosis formation in AF involves many complex mechanisms. Understanding the factors involved in thrombosis
formation and the clinically relevant comorbidities that affect thrombus formation is critical to developing new and more
effective treatment modalities. This will not only affect patients directly in terms of reducing morbidity and mortality, but
also help to address and mitigate the astronomical costs of treating this epidemic disease.
REFERENCES
[1] Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart
Study. Circulation September 8, 1998;98(10):946e52.
[2] Moe GK. On the multiple wavelet hypothesis of atrial fibrillation. Arch Int Pharmacodyn 1962:183e8.
[3] Haissaguerre M, Jais P, Shah DC, Takahashi A, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins.
N Engl J Med 1998;339:659e66.
[4] Krummen DE, Swarup V, Narayan SM. The role of rotors in atrial fibrillation. J Thorac Dis February 2015;7(2):142e51.
[5] 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of
Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014;130(23):2071e104.
[6] Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based
estimates. Am J Cardiol October 16, 1998;82(8A):2Ne9N.
[7] Frost L, Hune LJ. Vestergaard POverweight and obesity as risk factors for atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study. Am
J Med May 2005;118(5):489e95.
[8] January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland Jr JC, et al. 2014 AHA/ACC/HRS guideline for the management of patients
with atrial fibrillation. J Am Coll Cardiol 2014;64(21):2246e80.
[9] Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation
February 25, 2014;129(8):837e47.
[10] Kodani E, Atarashi H. Prevalence of atrial fibrillation in Asia and the world. J Arrhythmia December 2012;28(6):330e7.
[11] Tsang TS, Barnes ME, Miyasaka Y, Cha SS, Bailey KR, et al. Obesity as a risk factor for the progression of paroxysmal to permanent atrial
fibrillation: a longitudinal cohort study of 21 years. Eur Heart J September 2008;29(18):2227e33.
[12] Agency for Healthcare Research, Quality. Weighted national estimates. HCUP national inpatient sample [online]. 2012. Available from: http://
hcupnet.ahrq.gov/HCUPnet.jsp.
[13] Centers for Disease Control and Prevention. About multiple cause of death 1999e2011. CDC WONDER Online Database. 2014. Available from:
http://wonder.cdc.gov/mcd-icd10.html.
[14] Kim MH, Johnston SS, Chu B-C, et al. Estimation of total incremental health care costs in patients with atrial fibrillation in the United States.
Circulation Cardiovasc Quality Outcomes 2011;4:313e20.
[15] Reynolds MR, Essebag V. Economic-burden-of-atrial-fibrillation-implications-for-intervention. Am J Pharm Benefits 2012;4(2):58e65.
352 Cardiovascular Thrombus
https://t.me/med1917
[16] Morillo CA, Klein GJ, Jones DL, Guiraudon CM. Chronic rapid atrial pacing: structural, functional, and electrophysiological characteristics of a new
model of sustained atrial fibrillation. Circulation 1995;91:1588e95.
[17] Goette A, Honeycutt C, Langberg JJ. Electrical remodeling in atrial fibrillation time course and mechanisms. Circulation 1996;94:2968e74.
[18] Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation August 19,
1997;96(4):1180e4.
[19] Clement-Guinaudeau S, Montaudon M, Laurent F, Jaïs P, Cochet H. Atrial late gadolinium enhancement on MRI relates to the electrophysiological
substrate of persistent atrial fibrillation. J Cardiovasc Magn Reson 2015;17(suppl. 1).
[20] Oakes RS, Badger TJ, Kholmovski EG. Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic
resonance imaging in patients with atrial fibrillation. Circulation 2009;119:1758e67.
[21] Tiwari S, Løchen ML, Jacobsen BK, Hopstock LA, Nyrnes A, et al. Left atrial size and the risk of ischemic stroke in an ethnically mixed population.
CHA
DS-VASc score, left atrial size and atrial fibrillation as stroke risk factors in the Tromsø Study. Open Heart September 6, 2016;3(2).
[22] Di Tullio MR, Sacco RL, Sciacca RR, Homma S. Left atrial size and the risk of ischemic stroke in an ethnically mixed population. Stroke October
[23] Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg February
[24] Ono K, Iwama M, Kawasak M, Tanaka R, et al. Motion of left atrial appendage as a determinant of thrombus formation in patients with a low
[25] Castonguay MC, Wang Y, Gerhart JL, Miller DV, et al. Surgical pathology of atrial appendages removed during the cox-maze procedure: a review
[26] Masawa N, Yoshida Y, Yamada T, Joshita T, Ooneda G. Diagnosis of cardiac thrombosis in patients with atrial fibrillation in the absence of
[27] Mossard JM, Wiesel ML, Cazenave JP, et al. Relation of an increase of von Willebrand factor in the blood, acute myocardial infarction, unstable
[28] Freestone B, Chong AY, Nuttall S, Blann AD, et al. Soluble E-selectin, von Willebrand factor, soluble thrombomodulin, and total body nitrate/nitrite
[29] Scridon A, Girerd N, Rugeri L, Nonin-Babary E, Chevalier P. Progressive endothelial damage revealed by multilevel von Willebrand factor plasma
[30] Mondillo S, Sabatini L, Agricola E, et al. Correlation between left atrial size, prothrombotic state and markers of endothelial dysfunction in patients
[31] Freestone B, Chong AY, Nuttall S, Lip GY. Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial fibrillation
[32] Wu N, Tong S, Xiang Y, Wu L, Xu B, Zhang Y, et al. Association of Hemostatic Markers with Atrial Fibrillation: A Meta-Analysis and Meta-
[33] Atalar E, Haznedaroglu IC, Acil T, et al. Patients with paroxysmal atrial fibrillation but not paroxysmal supraventricular tachycardia display evi-
[34] Kamath S, Chin BS, Blann AD, Lip GY. A study of platelet activation in paroxysmal, persistent and permanent atrial fibrillation. Blood Coagul
[35] Colkesen Y, Acil T, Abayli B. Mean platelet volume is elevated during paroxysmal atrial fibrillation: a marker of increased platelet activation? Blood
[36] Tekin G, Tekin YK, Sivri N, Yetkin E. Mean platelet volume in patients with nonvalvular atrial fibrillation. Blood Coagul Fibrinolysis July
[37] Yuce M, Cakici M, Davutoglu V, et al. Relationship between mean platelet volume and atrial thrombus in patients with atrial fibrillation. Blood
[38] Roldán V, Marín F, Marco P, et al. Hypofibrinolysis in atrial fibrillation. Am Heart J December 1998;136(6):956e60.
[39] Wu N, Chen X, Cai T, et al. Association of inflammatory and hemostatic markers with stroke and thromboembolic events in atrial fibrillation: a
[40] Bruins P, Te Velthuis H, Yazdanbakhsh AP, et al. Activation of the complement system during and after cardiopulmonary bypass surgery: post-
[41] Guo Y, Lip GY, Apostolakis S. Inflammatory biomarkers and atrial fibrillation: potential role of inflammatory pathways in the pathogenesis of atrial
[42] Patel P, Dokainish H, Tsai P, Lakkis N. Update on the association of inflammation and atrial fibrillation. J Cardiovasc Electrophysiol September
[43] Psychari SN, Apostolou TS, Sinos L, et al. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes
[44] Melenovsky V, Lip GYH. Interleukine8 and atrial fibrillation. Europace 2008;10(7):784e5.
[45] Conway DS, Buggins P, Hughes E, Lip GY. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial
2
1999;30(10):2019e24.
1996;61(2):755e9.
CHADS
of 86 cases (2004 to 2005) with implications for prognosis. Am J Surg Pathol June 2013;37(6):890e7.
macroscopically visible thrombi. Virchows Arch a Pathol Anat Histopathol 1993;422(1):67e71.
angina and coronary thrombosis. Arch Mal Coeur Vaiss November 1989;82(11):1813e8.
product as indices of endothelial damage/dysfunction in paroxysmal, persistent, and permanent atrial fibrillation. Chest October
2007;132(4):1253e8.
concentrations in atrial fibrillation patients. Europace November 2013;15(11):1562e6.
with lone chronic nonrheumatic atrial fibrillation. Int J Cardiol September 15, 2000;75(2e3):227e32.
relationship to plasma von Willebrand factor and soluble E-selectin levels. Thromb Res 2008;122(1):85e90.
Regression. PLoS ONE 2015;10(4):e0124716. https://doi.org/10.1371/journal.pone.0124716.
dence of platelet activation during arrhythmia. Platelets NovembereDecember 2003;14(7e8):407e11.
Fibrinolysis October 2002;13(7):627e36.
Coagul Fibrinolysis July 2008;19(5):411e4.
2013;24(5):537e9.
Coagul Fibrinolysis 2010;21:722e5.
systematic review and meta-analysis. Can J Cardiol March 2015;31(3):278e86.
surgery activation involves c-reactive protein and is associated with postoperative arrhythmia. Circulation 1997;96(10):3542e8.
fibrillation-induced thromboembolism. Curr Vasc Pharmacol 2015;13(2):192e201.
2010;21(9):1064e70.
in patients with atrial fibrillation. Am J Cardiol 2005;95:764e7.
fibrillation. Am Heart J 2004;148:462e6.
score receiving warfarin for persistent nonvalvular atrial fibrillation. Cardiovasc Ultrasound 2012;10:50.
2
Thrombosis in Atrial Fibrillation Chapter | 23 353
https://t.me/med1917
[46] Lip GY, Patel JV, Hughes E, Hart RG. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet acti-
vation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke
2007;38:1229e37.
[47] Maehama T, Okura H, Imai K, Saito K, Yamada R, Koyama T, et al. Systemic inflammation and left atrial thrombus in patients with non-rheumatic
atrial fibrillation. J Cardiol 2010;56:118e24.
[48] Wolf PA, D Abbott R, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983e8.
[49] Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology
August 7, 2007;69(6):546e54.
[50] Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation:
analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF). Investigators. Stroke June
1999;30(6):1223e9.
[51] Varughese GI, Patel JV, Tomson J, et al. The prothrombotic risk of diabetes mellitus in atrial fibrillation and heart failure. J Thromb Haemost
2005;3:2811e3.
[52] Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five
randomized controlled trials. Arch Intern Med 1994;154:1449e57.
[53] Aronow WS, Ahn C, Kronzon I, et al. Risk factors for new thromboembolic stroke in patients 62 years of age with chronic atrial fibrillation. Am J
Cardiol 1998;82:119e21.
[54] The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Transesophageal echocardiography correlates of
thromboembolism in high-risk patients with nonvalvular atrial fibrillation. Ann Intern Med 1998;128:639e47.
[55] Olesen JB, Lip GY, Lane DA, Kober L, Hansen ML, Karasoy D, Hansen CM, Gislason GH, Torp-Pedersen C. Vascular disease and stroke risk in
atrial fibrillation: a nationwide cohort study. Am J Med 2012;125:e813e23.
[56] Atrial Fibrillation Investigators. Echocardiographic predictors of stroke in patients with atrial fibrillation. A prospective study of 1066 patients from
3 clinical trials. Arch Intern Med 1998;158:1316e20.
[57] Fang MC, Singer DE, Chang Y, et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation. The anti-
coagulation and risk factors in atrial fibrillation (ATRIA). Study Circulation September 20, 2005;112(12):1687e91.
[58] Zimmerman D, Sood MM, Rigatto C, et al. Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in
patients on dialysis. Nephrol Dial Transplant October 2012;27(10):3816e22.
[59] Bansal N, Fan D, Hsu CY. Incident atrial fibrillation and risk of death in adults with chronic kidney disease. J Am Heart Assoc October 20,
2014;3(5).
[60] Lau YC, Proietti M, Guiducci E. Atrial fibrillation and thromboembolism in patients with chronic kidney disease. J Am Coll Cardiol September
2016;68(13):1452e
[61] Qi Z, Chen H, Wen Z, et al. Relation of low-density lipoprotein cholesterol to ischemic stroke in patients with nonvalvular atrial fibrillation. Am J
Cardiol January 25, 2017. https://doi.org/10.1016/j.amjcard.2016.12.031.
[62] a Aakre CA, McLeod CJ, et al. Comparison of clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation. Stroke
2014;45:426e31.
b Odum LE, Cochran KA, Aistrope DS, Snella KA. The CHADS₂ versus the new CHA
treatment of patients with atrial fibrillation: review of the literature and recommendations for use. Pharmacotherapy March 2012;32(3):285e96.
[63] Calenda BW, Granger CB. ACP Journal Club. In atrial fibrillation, the ATRIA risk score better predicted stroke than CHADS
scores. Ann Intern Med February 16, 2016;164(4).
[64] Schweizer P, Bardos P, Erbel R, Meyer J, Merz W, Mesmer BJ, et al. Detection of left atrial thrombi by echocardiography. Br Heart J
1981;45:148e56.
[65] DePace NL, Soulen RL, Kotler MN, Mintz GS. Two dimensional echocardiographic detection of intra atrial masses. Am J Cardiol 1981;48:954e60.
[66] Manning WJ, Weintraub RM, et al. Accuracy of transesophageal echocardiography for identifying left atrial thrombi: a prospective, intraoperative
study. Ann Intern Med 1995;123:817e22.
[67] Hwang JJ, Chen JJ, Lin SC, et al. Diagnostic accuracy of transesophageal echocardiography for detecting left atrial thrombi in patients with
rheumatic heart disease having undergone mitral valve operations. Am J Cardiol 1993;72:677e81.
[68] Romero J, Husain SA, Kelesidis I, et al. Detection of left atrial appendage thrombus by cardiac computed tomography in patients with atrial
fibrillation a meta-analysis circ cardiovasc imaging 2013;6:185e94.
[69] Kitkungvan D, Nabi F, Ghosn MG. Detection of LA and LAA thrombus by CMR in patients referred for pulmonary vein isolation. JACC J Am Coll
Cardiol 2016;9(7):809e18.
[70] Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann
Intern Med June 19, 2007;146(12):857e67.
[71] Van Walraven C, Hart RG, Connolly S, Austin PC, et al. Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial
fibrillation investigators. Stroke April 2009;40(4):1410e6.
[72] Dlott JS, George RA, Huang X, et al. National assessment of warfarin anticoagulation therapy for stroke prevention in atrial fibrillation clinical
perspective. Circulation 2014;129:1407e14.
[73] Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med September
2009;361(12):1139e51.
64.
-VASc scoring systems for guiding antithrombotic
2DS2
and CHA2DS2-VASc
2
354 Cardiovascular Thrombus
https://t.me/med1917
[74] Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981e92.
[75] Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883e91.
[76] Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093e104.
[77] Hicks T, Stewart F, Eisinga A. NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis. Open Heart
2016;3:1e9.
[78] Ogilvie IM, Newton N, Welner SA, et al. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010;123:638e45.
[79] Calkins H, Kuck KH, Cappato R, et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation:
recommendations for patient selection procedural techniques, patient management and follow-up, definitions endpoints, and research trial design.
Europace 2012;14:528e606.
[80] Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients
with atrial fibrillation: a randomized non-inferiority trial. Lancet 2009;374:534e42.
[81] Reddy VY, Sievert H, Halperin J, PROTECT AF Steering Committee, Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial
fibrillation: a randomized clinical trial. J Am Med Assoc November 19, 2014;312(19):1988e98.
[82] Holmes Jr DR, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with
atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol July 8, 2014;64(1):1e12.
[83] Tzikas A, Shakir S, Gafoor S, et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the
AMPLATZER Cardiac Plug. Euro Interv February 2016;11(10):1170e9.
[84] Lakkireddy D, Afzal MR, Lee RJ, et al. Short and long-term outcomes of percutaneous left atrial appendage suture ligation: results from a US
multicenter evaluation. Heart Rhythm May 2016;13(5):1030e6.
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