Atrial fibrillation (AF) can induce a hypercoagulable state in both the left and right atria. Thrombus in the right side of the heart (RHT) may lead to acute pulmonary embolism (APE). The aim of the study was to determine the prevalence of RHT and AF and to assess their impact on outcomes in patients with APE. The retrospective cohort included 1,006 patients (598 female), with a mean age of 66 ± 15 years. The primary end point was all-cause mortality. The secondary end point was incidence of complications (death, cardiogenic shock, cardiac arrest, vasopressor/inotrope treatment, or ventilatory support). Atrial fibrillation was detected in 231 patients (24%). RHT was observed in 50 patients (5%). The combination of AF and RHT was observed in 16 patients (2%). The overall mortality rate was significantly higher in patients with RHT compared with those without (32% vs 14%, respectively, odds ratio [OR] 3.0, 95% confidence interval [CI] 1.6 to 5.6, p = 0.001). The rate of complications was significantly higher in patients with RHT in comparison to those without (40% vs 22%, respectively, OR 2.4, 95% CI 1.3 to 4.4, p = 0.004). The mortality rate in patients with both AF and RHT was significantly higher in comparison to those with AF but without RHT (50% vs 20%, respectively, OR 3.86, 95% CI 1.3 to 11.2, p = 0.01). In multivariate analysis, RHT (p = 0.03) was an independent predictor of death. In conclusion, AF is a frequent co-morbidity in patients with APE, and the presence of RHT is not uncommon. Among patients with APE, the presence of RHT increases the mortality approximately threefold regardless of the presence of known AF.
The association between ischemic stroke and systemic emboli arising from left atrial thrombus in patients with atrial fibrillation (AF) is well described. The notion of a parallel right atrial process leading to pulmonary venous thromboemboli has also been proposed. This theory can be supported by the observation of spontaneous echocardiographic contrast in both atria in patients with right-sided cardiac abnormalities, including AF. Where it has been shown that the presence of AF provokes a hypercoagulable state and induces platelet aggregation, it would seem sensible to infer that the hypercoagulable state exists in both the right and left atria. Reports that predate the era of widespread anticoagulation for patients with AF indicate that thrombus can develop in the right atrium. The landmark autopsy study by Aberg in 693 consecutive patients with AF showed that 13% of patients had clots in the left atrium and 8% had clots in the right atrium and that these occurred predominantly in the appendages. The risk stratification of patients with acute pulmonary embolism (APE) remains a challenge. Exploration of the link between APE, AF, and right heart thrombus (RHT) may provide further information about the pathophysiology of these disease processes and aid in risk stratification for patients with APE. The aim of this study was to determine the prevalence of RHT and AF and to assess their impact on outcomes in patients with APE.
Methods
This was a retrospective analysis of consecutive patients who were diagnosed with APE and were hospitalized in the cardiology departments of 8 community hospitals in 2 countries from 2004 to 2012. All clinical data were collected at the time admission or at the first occurrence during the hospitalization. The presence of thrombus in the right atrium and ventricle was assessed by echocardiography or computed tomography with angiography (CTA). CTA was performed immediately when APE was suspected. Echocardiography was performed as the primary diagnostic investigation when a patient was in cardiogenic shock, was experiencing chest pain, or after CTA when APE was confirmed. Transthoracic echocardiography was performed using dedicated echocardiographic systems equipped with 3.5-MHz phased array probes. During echocardiographic examination, masses in the right side of the heart were reported as thrombi when their echodensity differed from the blood and heart structures or when these demonstrated their own pattern of motion. Poorly defined structures seen in the heart cavities were not reported as thrombi. Only CTA examinations with “good” image quality were interpreted. Thrombi were reported when filling defects with low attenuation and distinct borders surrounded by contrast medium were detected within the right side of the heart.
Standard 12-lead surface electrocardiograms (ECGs) were recorded with a paper speed of 25 to 50 mm/s. The first available ECG was used for analysis. This ECG was assessed for the presence of AF. In 4 patients, the admission ECG was not of appropriate technical quality to assess for AF. All patients were divided into 2 subgroups according to the pattern of AF: (1) AF (−) group—patients without a known medical history of AF, in sinus rhythm on admission, and without detectable AF during the hospitalization and (2) AF (+) group—patients with a known medical history of AF and those who were found to be in AF at some point during the hospital admission (paroxysmal, persistent, or permanent AF). Patients were further classified as paroxysmal or nonparoxysmal (persistent or permanent).
Low blood pressure (BP) was defined as ≤90/60 mm Hg. Elevated heart rate (HR) was defined as ≥100 beats/min. HR on admission was defined as the HR assessed from ECG recorded on admission. Right ventricular overload was defined by the presence of at least one of the following echocardiographic parameters: right ventricular diameter ≥30 mm in the parasternal view or RV/LV ratio >1, acceleration time of right ventricular (RV) ejection <90 ms or tricuspid insufficiency peak gradient >30 mm Hg without RV hypertrophy, paradoxical systolic movement of the septum, presence of hypokinesia or akinesia of the RV free wall, or presence of RHT. Obesity was defined as body mass index ≥30 kg/m 2 .
The primary end point was all-cause mortality during the index hospitalization. The secondary end point was incidence of complications (a composite of death, cardiogenic shock, cardiac arrest, vasopressor/inotrope treatment, or mechanical ventilatory support).
Categorical variables are expressed as numbers and percentages and continuous variables as means and SDs. The statistical significance of differences between 2 groups was assessed using a univariate logistic regression model in which the direction and strength of an association between a grouping variable and a predictor were summarized by the odds ratio (OR) with a 95% confidence interval (CI). The multivariate logistic regression model, due to a noticeable fraction of data missing in few clinically relevant predictors, was estimated using the method of multiple imputation by chained equations (imputation model was random forests, 100 imputed data sets were created). A 2-tailed p value <0.05 was considered statistically significant. All statistical analyses were performed using R 3.0 (R Foundation for Statistical Computing).
Results
The study group consisted of 1,006 consecutive patients (598 female) with a mean age of 66 ± 15 years and an age range of 17 to 98 years. APE was diagnosed by CTA in 709 patients (71%), ventilation/perfusion scintigraphy in 154 patients (15%), echocardiography in 138 patients (14%), and autopsy in 5 patients (0.5%). Of 1,006 patients, 31 were excluded because of a lack of information on the presence or absence of RHT, and 975 patients were included in the final analysis ( Figure 1 ). In 4 cases, the ECG obtained on admission was inadequate for evaluation, and those patients were excluded. Characteristics of the study population are described in Table 1 . RHT was detected in 50 patients (5%). The diagnosis of RHT was made by CTA with echocardiographic confirmation in 48 patients and by echocardiography alone in 2 patients. There were no differences between patients with and without RHT in terms of demographic parameters (age and gender), clinical symptoms (syncope and chest pain), co-morbidities (cancer, chronic obstructive pulmonary disease, heart failure, deep venous thrombosis, and obesity), or elevated troponin plasma concentration. Compared with patients without RHT, patients with RHT had lower systolic BP, higher HR, and a higher prevalence of echocardiographic RV overload. AF was identified in 24% of patients. The pattern of AF was paroxysmal in 6% of patients and permanent in 17%. In patients with AF, RHT was observed in 16 patients (7%), including 11 patients (7%) with nonparoxysmal AF and 5 patients (8%) with paroxysmal AF. There was no difference in the prevalence of RHT in patients with AF compared with patients without AF (16 [7%] vs 33 patients [5%], OR 1.6, 95% CI 0.8 to 2.9, p = 0.2).
| Variable | Overall (n= 975) | Right-Sided Heart Thrombus (-) (n=925) | Right-Sided Heart Thrombus (+) (n=50) | OR [95% CI] | p-value |
|---|---|---|---|---|---|
| Age (years) | 65.8 (14.7) | 65.9 (145) | 64.4 (17) | 0.9 [0.8-1.1] | 0.5 |
| Women | 576 (59%) | 547 (59%) | 29 (58%) | 1.0 [0.5-1.7] | 09 |
| Atrial Fibrillation | 231 (24%) | 215 (23%) | 16 (33%) | 1.6 [0.8-2.9] | 0.1 |
| Pattern of Atrial Fibrillation | |||||
| Paroxysmal | 60 (6%) | 55 (56%) | 5 (10%) | 2.0 [0.7-4.9] | 0.2 |
| Permanent | 169 (17%) | 158 (17%) | 11 (22%) | 1.5 [0.7-3.0] | 0.3 |
| Fibrinolysis | 82 (8%) | 72 (8%) | 10 (20%) | 3.0 [1.4-6.0] | 0.009 |
| Syncope | 215 (22%) | 204 (22%) | 11 (22%) | 1.0 [0.5-1.9] | 1.0 |
| Chest pain | 434 (45%) | 418 (45%) | 16 (32%) | 0.6 [0.3-1.0] | 0.07 |
| Chronic obstructive pulmonary disease | 93 (10%) | 90 (10%) | 3 (6%) | 0.6 [0.1-1.7] | 0.404 |
| Heart failure | 116 (12%) | 110 (12%) | 6 (12%) | 1.0 [0.4-2.3] | 0.9 |
| Obesity | 184 (19%) | 177 (19%) | 7 (14%) | 0.7 [0.3-1.5] | 0.4 |
| Cancer | 126 (13%) | 119 (13%) | 7 (14%) | 1.1 [0.5-2.4] | 0.8 |
| Active infection | 122 (13%) | 115 (12%) | 7 (14%) | 1.2 [0.5-2.5] | 0.7 |
| Immobilization | 218 (22%) | 199 (22%) | 19 (38%) | 2.2 [1.2-4.0] | 0.01 |
| Deep Venous Thrombosis | 371 (38%) | 355 (39%) | 16 (33%) | 0.8 [0.4-1.4] | 0.4 |
| Systolic blood pressure ∗ [mmHg] | 124 (32) | 125 (31) | 108 (48) | 0.9 [0.8-1.0] per 10 mmHg | 0.004 |
| Diastolic blood pressure ∗ [mmHg] | 76 (19) | 76.4 (9) | 69.9 (29) | 0.9 [0.7-1.0] per 10 mmHg | 0.07 |
| Heart Rate ∗ [bpm] | 101 (27) | 101 (27) | 109 (22) | 1.1 [1.0-1.2] per 10 bpm | 0.04 |
| Elevated cTnT ∗ | 340 (57%) | 323 (57%) | 17 (65%) | 1.4 [0.6-3.5] | 0.4 |
| Vasopressors/Inotropes | 219 (23%) | 199 (22%) | 20 (40%) | 2.4 [1.3-4.4] | 0.004 |
| Death | 141 (15%) | 125 (14%) | 16 (32%) | 3.0 [1.6-5.6] | 0.001 |
| Catecholamines | 105 (11%) | 95 (10%) | 10 (20%) | 2.3 [1.0-4.5] | 0.04 |
| Shock | 126 (13%) | 114 (12%) | 12 (24%) | 2.3 [1.1-4.3] | 0.03 |
| Right Ventricular Overload ∗ | 661 (76%) | 614 (75%) | 47 (94%) | 5.1 [1.8-21.8] | 0.001 |
∗ Missing data for systolic and diastolic BP ∼ 30%, for HR ∼ 15%, for cTnT ∼ 38%, for RV overload ∼14%.
Data on the rates of mortality and complications in patients with and without AF according to the presence or absence of RHT are provided in Table 2 . The mortality rate was twice as high in patients with AF as compared with patients without AF, and the rate of complications was also significantly higher in patients with AF than in patients without AF. The mortality rate of patients with both AF and RHT was significantly higher than those with AF but without RHT. Similarly, in patients with RHT but without AF, the mortality rate was twice as high as in those with neither AF nor RHT. The mortality rate was 3 times as high in patients with RHT as compared with those without (32% vs 14%, respectively, OR 3.0, 95% CI 1.6 to 5.6, p = 0.001). The rate of complications was twice as high in patients with RHT as compared with those without (40% vs 21.5%, respectively, OR 2.44, 95% CI 1.33 to 4.37, p = 0.004). Cardiogenic shock was twice as common in patients with RHT as compared with those without (24% vs 11%, respectively, OR 2.3, 95% CI 1.1 to 4.3, p = 0.03). Of 126 patients classified as high risk by European Society of Cardiology criteria, RHT was detected in 10% of patients. Of 849 patients not classified as high risk, RHT was detected in 5% of patients.
| Group | n | Mortality Rate | OR, [95 % CI] | Complication Rate | OR, [95% CI] |
|---|---|---|---|---|---|
| AF + | 231 | 23% | 2.1 [1.4-3.0] p < 0.001 | 31% | 1.8 [1.3-2.5] p < 0.001 |
| AF – | 740 | 12% | 20% | ||
| AF + / RHT + | 16 | 50% | 3.9 [1.3-11.2] p = 0.01 | 56% | 3.1 [1.1-9.1] p = 0.04 |
| AF + / RHT – | 215 | 20% | 29% | ||
| AF – / RHT + | 33 | 24% | 2.6 [1.0-5.7] p = 0.04 | 33% | 2.2 [1.0-4.5] p = 0.06 |
| AF – / RHT – | 707 | 11% | 19% |
Univariate analysis revealed an association of death with age (p = 0.03), history of heart failure (p = 0.007), active infection (p = 0.007), immobilization (p = 0.001), lower systolic BP (p <0.001), higher HR (p <0.001), presence of AF at admission (p <0.001), elevated cardiac troponin T (p <0.001), vasopressor/inotrope treatment (p = 0.000), RHT (p = 0.001), and echocardiographic RV overload (p <0.001). In multivariate analysis, independent predictors of death were as follows: RHT (p = 0.03), age (p = 0.005), HR on admission (p = 0.02), shock (p = 0.000), and echocardiographic RV overload (p = 0.01). AF was not associated with death (p = 0.2). Detailed results are provided in Table 3 .
| Variable | Prevalence | Univariate Analysis | Multivariate Analysis | ||||
|---|---|---|---|---|---|---|---|
| Overall | Survivors | Non-Survivors | OR 95% CI | p-value | OR 95% CI | p-value | |
| Age (years) | 65.8 (14) | 65.3 (15) | 69.3 (14) | 1.2 [1.1-1.4] per 10 years | 0.003 | 1.3 [1.1-1.5] per 10 years | 0.005 |
| Women | 576 (59%) | 489 (59%) | 87 (62%) | 1.1 [0.8-1.7] | 0.5 | 1.2 [0.7-1.8] | 0.5 |
| Atrial Fibrillation | 231 (24%) | 179 (22%) | 52 (37%) | 2.2 [1.5-3.2] | <0.001 | 1.4 [0.8-2.3] | 0.2 |
| Pattern of Atrial Fibrillation | |||||||
| Paroxysmal | 60 (6%) | 51 (6%) | 9 (6%) | 1.3 [0.6-2.7] | 0.5 | 0.8 [0.3-1.9] | 0.6 |
| Permanent | 169 (17%) | 126 (15%) | 43 (31%) | 2.6 [1.7-3.9] | <0.001 | 1.6 [0.9-2.8] | 0.1 |
| Right-sided Heart Thrombus | 50 (5%) | 34 (4%) | 16 (11%) | 3.0 [1.6-5.6] | 0.001 | 2.4 [1.1-5.0] | 0.03 |
| Heart Rate ∗ (bpm) | 101 (27) | 99.3 (27) | 114 (24) | 1.2 [1.1-1.3] per 10 bpm | <0.001 | 1.1 [1.0-1.2] per 10 bpm | 0.02 |
| Elevated cTnT ∗ | 340 (57%) | 290 (55%) | 50 (77%) | 2.8 [1.5-5.2] | <0.001 | 1.7 [1.0-3.0] | 0.05 |
| Shock | 126 (13%) | 56 (7%) | 70 (50%) | 14.0 [9.2-21.6] | 0.000 | 10 [4.5-22.1] | 0.000 |
| Right ventricular overload ∗ | 661 (75%) | 558 (73%) | 103 (92%) | 4.1 [2.1-8.9] | <0.001 | 2.5 [1.2-5.2] | 0.01 |
| Vasopressors / Inotropes | 105 (11%) | 52 (6%) | 53 (38%) | 9.3 [6.0-14.6] | 0.000 | 1.2 [0.5-2.6] | 0.7 |
| Heart failure | 116 (12%) | 89 (11%) | 27 (19%) | 2.0 [1.2-3.2] | 0.007 | 1.4 [0.8-2.5] | 0.2 |
| Cancer | 126 (13%) | 108 (13%) | 18 (13%) | 1.0 [0.6-1.7] | 1.0 | 1.3 [0.7-2.4] | 0.5 |
| Systolic Blood Pressure ∗ (mmHg) | 124 (32) | 128 (30) | 99.7 (37) | 0.8 [0.7-0.8] per 10 mmHg | <0.001 | 1.0 [0.9-1.1] per 10 mmHg | 0.5 |
| Diastolic Blood pressure ∗ (mmHg) | 76.1 (19) | 78.1 (18) | 60.5 (24) | 0.7 [0.6-0.8] per 10 mmHg | <0.001 | ||
| Chest pain | 434 (45%) | 401 (48%) | 33 (23%) | 0.3 [0.2-0.5] | <0.001 | ||
| Active infection | 122 (13%) | 94 (11%) | 28 (20%) | 2.0 [1.2-3.1] | 0.007 | ||
| Immobilization | 218 (22%) | 170 (20%) | 48 (34%) | 2.0 [1.4-3.0] | 0.001 | ||
| Deep Venous Thrombosis | 371 (38%) | 341 (41%) | 30 (22%) | 0.4 [0.3-0.6] | <0.001 | ||
| Chronic Obstructive Pulmonary Disease | 93 (10%) | 81 (10%) | 12 (9%) | 0.9 [0.4-1.6] | 0.7 | ||
| Obesity | 184 (19%) | 165 (20%) | 19 (14%) | 0.6 [0.4-1.0] | 0.07 | ||
| Syncope | 215 (22%) | 177 (21%) | 38 (27%) | 1.4 [0.9-2.0] | 0.1 | ||
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
