In the whole group of 267 patients, 77 (29%) were diagnosed with thrombus or sludge. The baseline characteristics of patients with and without LAA thrombus or sludge are shown in Table 1. Among the group with thrombus or sludge in LAA, 9% were not adequately treated with anticoagulants before TOE (either no anticoagulation or anticoagulation shorter than 3 weeks or warfarin with TTR < 80% or LMWH in prophylactic dose), 3% received therapeutic doses of LMWH, 54% received NOAC, and 34% received VKA. In Additional Table 3 we have presented characteristics of patients subjected to further TOE control. Additional Table 3shows no significant differences in baseline characteristics between patients who succeeded or failed in thrombus resolution.
Table 1
Baseline characteristics of patients with and without thrombus or sludge
| Thrombus or sludge (+) N = 77 | Thrombus or sludge (-) N = 190 | p-value |
Clinical |
Age /mean | 74.99 ± 8.17 | 73.01 ± 10.19 | 1.000 |
Female sex / number of patients (percentage) | 42 (54.54) | 82 (43.16) | 0.092 |
CHA2DS2VASc / mean | 4.70 (4.00–6.00) | 4.00 (3.00–5.00) | 0.101 |
CHA2DS2VASc > 3 / number of patients (percentage) | 61 (79.22) | 138 (72.63) | 0.264 |
First episode of AF/AFl/ number of patients (percentage) | 23 (29.87) | 92 (48.42) | 0.006 |
Atrial flutter / number of patients (percentage) | 12 (15.58) | 41 (21.58) | 0.267 |
Arrhythmia episode duration in weeks / mean | 53.91 ± 108.23 | 22.53 ± 40.99 | 0.011 |
BMI (kg/m2) /mean | 29.06 ± 5.35 | 29.11 ± 4.94 | 0.942 |
Overweight / number of patients (percentage) | 31 (40.26) | 79 (41.58) | 0.843 |
Obesity / number of patients (percentage) | 29 (37.66) | 69 (36.32) | 0.837 |
Arterial hypertension / number of patients (percentage) | 63 (81.82) | 147 (77.37) | 0.422 |
Diabetes / number of patients (percentage) | 35 (45.45) | 68 (35.79) | 0.142 |
Previous stroke/TIA / number of patients (percentage) | 17 (22.08) | 42 (22.11) | 0.996 |
Vascular disease / number of patients (percentage) | 49 (63.64) | 100 (52.63) | 0.102 |
Congestive heart failure / number of patients (percentage) | 39 (50.65) | 72 (37.89) | 0.056 |
Active cancer / number of patients (percentage) | 2 (2.60) | 7 (3.68) | 0.656 |
Cancer in medical history / number of patients (percentage) | 6 (7.79) | 16 (8.42) | 0.866 |
Smoking / number of patients (percentage) | 4 (5.19) | 7 (3.68) | 0.574 |
Active inflammation / number of patients (percentage) | 5 (6.49) | 14 (7.37) | 0.802 |
Infection in last 3 months / number of patients (percentage) | 16 (20.78) | 33 (17.37) | 0.515 |
Surgery in last 3 months / number of patients (percentage) | 4 (5.19) | 12 (6.32) | 0.727 |
Echocardiography |
LVEF / mean | 43.36 ± 12.48 | 46.24 ± 11.72 | 0.075 |
LA area/ mean | 30.18 ± 10.26 | 27.05 ± 5.22 | 1.000 |
Presence of spontaneous echo contrast / number of patients (percentage) | 56 (72.73) | 62 (32.63) | < 0.0001 |
Low LAA velocities / number of patients (percentage) | 68 (88.31) | 113 (59.47) | < 0.0001 |
Aortic stenosis moderate-to-severe / number of patients (percentage) | 4 (5.19) | 13 (6.84) | 0.618 |
Aortic regurgitationmoderate-to-severe / number of patients (percentage) | 2 (2.60) | 6 (3.16) | 0.808 |
Mitral stenosis moderate-to-severe / number of patients (percentage) | 3 (3.90) | 1 (0.53) | 0.040 |
Mitral regurgitation moderate-to-severe / number of patients (percentage) | 18 (23.38) | 50 (26.32) | 0.618 |
Aortic prosthesis / number of patients (percentage) | 4 (5.19) | 8 (4.21) | 0.726 |
Mitral prosthesis / number of patients (percentage) | 4 (5.19) | 5 (2.63) | 0.294 |
Laboratory |
Creatinine mean(mg/dl) | 0.99 ± 0.38 | 1.01 ± 0.41 | 0.713 |
Haematocrit mean (%) | 40.46 ± 4.54 | 40.63 ± 4.68 | 0.787 |
Platelets mean (G/l) | 213.19 ± 54.87 | 220.07 ± 82.79 | 0.503 |
INR mean | 1.90 ± 0.89 | 1.73 ± 0.72 | 1.000 |
aPTT ratio mean | 1.34 ± 0.40 | 1.30 ± 0.33 | 1.000 |
Anticoagulation |
Anticoagulation / number of patients (percentage) | 70 (90.91) | 168 (88.42) | 0.555 |
Anticoagulation duration in weeks / mean | 111.73 ± 201.73 | 123.05 ± 235.11 | 0.711 |
Anticoagulation >4 weeks / number of patients (percentage) | 66 (85.71) | 159 (83.68) | 0.680 |
NOAC / number of patients (percentage) | 37 (48.05) | 122 (64.21) | 0.015 |
Vitamin K antagonists with TTR > 85% / number of patients (percentage) | 29 (37.66) | 43 (22.63) | 0.012 |
No anticoagulation or shorter than 3 weeks or warfarin with TTR < 80% or LMWH in prophylactic dose / number of patients (percentage) | 7 (9.09) | 20 (12.35) | 0.725 |
Anticoagulation interruption in last three months / number of patients (percentage) | 12 (15.58) | 11 (5.79) | 0.01 |
Cardiologist-controlled anticoagulation / number of patients (percentage) | 41/59 (69.49) | 100/143 (69.93) | 0.951 |
Mini Mental State Examination |
MMSE score / mean | 24.80 ± 4.30 | 26.62 ± 3.38 | < 0.001 |
Mild impairment of congnitive function / number of patients (percentage) | 16 (20.78) | 30 (15.79) | 0.329 |
Dementia / number of patients (percentage) | 6 (7.79) | 2 (1.05) | 0.0035 |
Table 2
The comparison of ischaemic strokes and mortality in thrombus or sludge vs no thrombus nor sludge (Fisher)
| Thrombus/Sludge (+) | Thrombus/Sludge (-) | n |
Ischemic stroke event (%) | 13 (17%) | 2 (1%) | 15 |
No ischemic stroke event (%) | 64 (83%) | 188 (99%) | 252 |
n | 77 | 190 | Total 267 |
Test Fisher exact p < 0.001 |
One-year mortality (%) | 18 (23%) | 3 (1.6%) | 21 |
One-year survivors (%) | 59 (77%) | 187 (98.4%) | 246 |
n | 77 | 190 | Total 267 |
Test Fisher exact p < 0.001 |
Table 3
The comparison of ischaemic strokes and mortality in sludge vs no thrombus nor sludge (Fisher)
| Sludge (+) | No Thrombus/Sludge | n |
Ischemic stroke event (%) | 2 (11%) | 2 (1%) | 4 |
No ischemic stroke event (%) | 17 (89%) | 188 (99%) | 205 |
n | 19 | 190 | Total 209 |
Test Fisher exact p < 0.042 |
One-year mortality (%) | 2 (11%) | 3 (1.6%) | 6 |
One-year survivors (%) | 17 (89%) | 187 (98.3%) | 203 |
n | 19 | 190 | Total 209 |
Test Fisher exact p < 0.066 |
Risk of ischemic stroke and annual mortality
After a one-year follow-up with the thrombus or sludge group, 18 patients had died (23%) and 13 (17%) had experienced ischemic stroke. In the group without thrombus or sludge, three patients (1.6%) had died and two (1%) had experienced non-fatal ischemic stroke(Table 2). The odds ratio (OR) for mortality was 19.01 (95% confidence interval [CI]: 5.4–66.8, p < 0.0001). The relative risk RR for mortality was 3.6 (95% CI: 2.7–4.7, p < 0.0001). The OR for ischemic stroke was 19.1 (95% CI: 4.2–86.9, p < 0.0001). The RR for ischemic stroke was 3.4 (95% CI 2.5–4.6, p < 0.0001). The OR for both mortality and ischemic stroke was 24.9 (95% CI: 9.2–67.7, p < 0.0001). Finally, the RR for both mortality and ischemic stroke was 4.3 (95% CI: 3.2–5.8, p < 0.0001).
Effectiveness of thrombus or sludge resolution in not-anticoagulated patients (Fig. 1)
Seven patients (9%) had not been previously treated with anticoagulants or had been treated inadequately. The group demonstrated high effectiveness of oral anticoagulants (5 patients were treated with NOAC, 2 patients with VKA)—in all of the patients subjected to control TOE, there were no instances of thrombus or sludge. Anticoagulant LMWH turned out to be the most effective treatment in thrombus or sludge resolution in the group of patients previously treated with OAC (9 out of 11 patients, 82%). NOACs and VKA had similar outcomes (NOACs: 8 out of 18 patients, 44%; VKA: 3 out of 7 patients, 43%), but their effectiveness was significantly lower than that of LMWH (p < 0.035). The number needed to treat to resolve thrombus or sludge LAA was 2.6 (95% CI: 1.4–20.7, p = 0.09).
Differences in risk of ischemic stroke and annual mortality between sludge vs. appendage free from thrombus or sludge
After a one-year follow-up with the group containing sludge patients, two patients had died (11%) and three (16%) had experienced ischemic stroke. In the group without thrombus or sludge, three patients had died (1.6%) and two (1%) had experienced ischemic stroke The statistical differences are significant in terms of stroke or borderline for 1-year mortality but based on small number of events so analysis and conclusions should be careful(Table 3).
No significant differences in risk of ischemic stroke and annual mortality between thrombus and sludge
Patients with sludge in the LAA experienced fewer strokes (2 out of 19, 11%) than those with thrombus (9 out of 58, 16%). There were also fewer deaths in patients with sludge (3 out of 19, 16%) than in patients with thrombus (14 out of 58, 24%), but the differences were not statistically significant (Table 4)
Table 4
The comparison of ischaemic strokes and mortality in sludge vs thrombus (Fisher)
| Sludge | Thrombus | n |
Ischemic stroke event (%) | 2 (11%) | 9 (16%) | 11 |
No ischemic stroke event (%) | 17 (89%) | 49 (84%) | 66 |
n | 19 | 58 | Total 77 |
Test Fisher exact p < 0.722 |
One-year mortality (%) | 3 (16%) | 14 (24%) | 17 |
One-year survivors (%) | 16 (84%) | 44 (76%) | 60 |
n | 19 | 58 | Total 77 |
Test Fisher exact p < 0.539 |
No significant differences in risk level between successful and unsuccessful thrombus/sludge resolution
Patients with dissolved thrombus or sludge in the LAA experienced fewer ischemic strokes (2 out of 26.8%) than those with persistent thrombus/sludge (2 out of 16; 12%). There were fewer deaths among patients with dissolved thrombus or sludge (4 out of 26; 15%) than among patients with persistent thrombus or sludge (4 out of 16; 25%), but the differences were not statistically significant (Table 5).
Table 5
The comparison of ischaemic strokes and mortality between patients with and without thrombus resolution (Fisher)
| Thrombus resolution (+) | Thrombus resolution (-) | n |
Ischemic stroke event (%) | 2 (8%) | 2 (12%) | 4 |
No ischemic stroke event (%) | 24 (92%) | 14 (88%) | 38 |
n | 26 | 16 | Total 42 |
Test Fisher exact p < 0.628 |
One-year mortality (%) | 4 (15%) | 4 (25%) | 8 |
One-year survivors (%) | 22 (85%) | 12 (75%) | 34 |
n | 26 | 16 | Total 42 |
Test Fisher exact p < 0.454 |
No significant differences in risk level between patients subjected to TOE control vs. those without further TOE control
After diagnosis of LAA thrombus, 34 patients (44%) were diagnosed with chronic arrhythmia and prescribed standard OAC. The TOE control was abandoned in this group. The remaining 43 patients (56%) underwent anticoagulation to dissolve thrombus. The latter group was subjected to further TOE control and directed to undergo cardioversion in the case of thrombus resolution. Patients with thrombus or sludge had fewer strokes (4 out of 43; 9%) and deaths (7 out of 43; 16%) if they were further treated with thrombus resolution and cardioversion. Patients who decided against further control and cardioversion had a higher number of strokes (7 out of 34; 21%) and deaths (10 out of 34; 29%), but the differences were not significant (Table 6).
Table 6
The comparison of ischaemic strokes and mortality between patients subjected to TOE control versus those without further TOE control (Fisher)
| TOE control (+) Intension for thrombus resolution | TOE control (-) | n |
Ischemic stroke event (%) | 4 (9%) | 7 (21%) | 11 |
No ischemic stroke event (%) | 39 (91%) | 27 (79%) | 66 |
n | 43 | 34 | Total 77 |
Test Fisher exact p < 0.198 |
One-year mortality (%) | 7 (16%) | 10 (29%) | 17 |
One-year survivors (%) | 36 (84%) | 24 (71%) | 60 |
n | 43 | 34 | Total 77 |
Test Fisher exact p < 0.181 |
No significant differences in risk level between patients treated with LMWH vs. OAC
Patients treated with LMWH had a lower risk of stroke (1 out of 12; 9%) than those treated with OAC (12 out of 16; 19%). The number of deaths in patients treated with LMWH (2 out of 12; 19%) was also lower than the number of deaths in the OAC group (16 out of 63; 25%). Neither of these differences were statistically significant (Table 7).
Table 7
The comparison of ischaemic strokes and mortality in persistent AF or AFl between LMWH and OAC (Fisher)
| LMWH | OAC | n |
Ischemic stroke event (%) | 1 (9%) | 4 (13%) | 5 |
No ischemic stroke event (%) | 10 (91%) | 27 (87%) | 37 |
n | 11 | 31 | Total 42 |
Test Fisher exact p < 1.0 |
One-year mortality (%) | 2 (18%) | 5 (16%) | 7 |
One-year survivors (%) | 9 (82%) | 26 (84%) | 37 |
n | 11 | 31 | Total 42 |
Test Fisher exact p < 1.0 |