Spontaneous echocardiographic contrast (SEC) is the presence of smoke-like echoes with a characteristic swirling motion of blood in echocardiography. Previous clinical studies have demonstrated that SEC is a risk factor for left atrial thrombus formation and an important indicator of potential systemic embolism originated from heart. An established relation exists between the inflammatory status and the prothrombotic state. Therefore, we investigated the role of inflammatory status on SEC in patients with mitral stenosis (MS). A total of 62 consecutive patients with MS who undergoing mitral balloon valvuloplasty were enrolled in the present study. The patients were divided into 2 groups according to the formation of SEC in the left atrium. Of the 62 patients, 32 (mean age 45 ± 12 years; 75% women) were in the SEC-negative group and 30 patients (mean age 45 ± 11 years; 63% women) were in the SEC-positive group. The high-sensitive C-reactive protein levels were significantly greater in the SEC-positive group than in the SEC-negative group (3.9 ± 2.2 vs 10.6 ± 6.3, p = 0.024). The neutrophil levels (64.6 ± 9.4 vs 72.6 ± 8.6) were significantly greater in the SEC-positive group, and the lymphocyte levels (24.4 ± 6.9 vs 18.3 ± 6.0) were significantly greater in the SEC-negative group (p = 0.001 for each). The neutrophil/lymphocyte (N/L) ratio was also significantly greater in the SEC-positive group (3.0 ± 1.8 vs 4.5 ± 1.8, p = 0.003). In the receiver operating characteristics curve analysis, a N/L ratio >3.1 mg/dl had a 80% sensitivity and 72% specificity in predicting SEC in patients with MS. On multivariate analysis, high-sensitive C-reactive protein (odds ratio [OR] 1.235, 95% confidence interval [CI] 1.040 to 1.466; p = 0.016), N/L ratio (OR 1.461, 95% CI 0.977 to 2.184; p = 0.02), left atrial volume (OR 3.012, 95% CI 1.501 to 5.611; p = 0.001), and mitral valve area (OR 0.135, 95% CI 0.020 to 0.503; p = 0.017) were independent risk factors of SEC in patients with MS. In conclusion, the high-sensitive C-reactive protein and N/L ratio were independently associated with SEC in patients with MS.
Spontaneous echocardiographic contrast (SEC) is the presence of smoke-like echoes with a characteristic swirling motion of blood found during echocardiography. SEC is commonly seen in the left atrium and is caused in particular by mitral stenosis (MS) and nonvalvular atrial fibrillation. Previous clinical studies have demonstrated that SEC is a risk factor for left atrial thrombus formation and an important indicator of potential systemic embolism originated from heart. An established relation exists between inflammatory status and the prothrombotic state. Also, the association of the inflammatory status with SEC in patients with atrial fibrillation has been previously demonstrated. The role of the inflammatory status on SEC in patients with MS is unknown. We investigated the role of inflammatory status on SEC in patients with MS.
Methods
A total of 62 consecutive patients (mean age 45 ± 11 years; 69% women) with MS who undergoing mitral balloon valvuloplasty were prospectively enrolled in the present study. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were performed for each patient to rule out the thrombus formation in the left atrium before mitral balloon valvuloplasty. The SEC was evaluated by TEE for all patients. The study population was divided into 2 groups according to the presence of SEC in the left atrium. Group 1 included those with MS complicated by SEC and group 2, those with MS without SEC.
The exclusion criteria for the present study were left atrial thrombus formation, a history of malignancy, a history of inflammatory disease, current therapy with corticosteroids and nonsteroidal anti-inflammatory drugs, connective tissue disease, thyroid disease, and other hematologic disease. A medical history was recorded from patient anamnesis. Atrial fibrillation was determined by electrocardiography. The blood pressure was measured after 10 minutes at rest before TTE with a random-zero sphygmomanometer by trained observers. The heart rate was recorded with the blood pressure measurement.
All patients provided informed consent, and the ethics committee and institutional review board of Erciyes University Medical School approved the protocol.
In all patients, antecubital venous blood samples for the laboratory analysis were taken immediately after TEE. Tripotassium ethylenediaminetetraacetic acid-based anticoagulated blood samples for common blood counting were measured using the Sysmex K-1000 auto-analyzer within 5 minutes of sampling. The samples were studied immediately to avoid platelet swelling. High-sensitive C-reactive protein (hs-CRP) was measured using a BN2 model nephlometer (Dade Behring Diagnostics, Inc., Newark, Delaware). Also, all routine biochemical tests were performed using an AutoAnalyzer (Roche Diagnostic Modular Systems, Tokyo, Japan).
Two-dimensional echocardiography was performed using a commercially available machine (Vivid 7, GE Medical System, Horten, Norway), with a 3.5-MHz transducer for TTE and 5-MHz for TEE, during ≥3 (for sinus rhythm) or ≥7 (for atrial fibrillation) consecutive cardiac cycles. TTE and TEE were performed during the same session. All patients were studied in the left lateral recumbent position after a 10-minute resting period. Simpson’s method in 2-dimensional echocardiographic apical 4-chamber view was used to assess the left ventricular ejection fraction, as recommended by the American Society of Echocardiography guidelines. The mitral valve area was measured using the planimetric method. The jet of tricuspid regurgitation was identified, its maximum velocity measured, and pressure gradient calculated. This gradient was added to an assumed right atrial pressure (10 mm Hg) to give an estimate of the systolic pulmonary artery pressure. For TEE, after patients had been administered pharyngeal local anesthesia with a lidocaine spray, the probe was initially carried forward to a depth of 25 to 35 cm and then manipulated for optimum imaging. All images were archived and evaluated by 2 independent echocardiographer cardiologists. SEC was defined as a pattern of slowly swirling intracavity echocardiographic densities imaged with gain settings adjusted to distinguished background noise. Intra- and interobserver variability were obtained from a random 40 patients. The intra- and interobserver variability for the presence of SEC were both 3%.
Continuous variables were tested for normal distribution using the Kolmogorov-Smirnov test. We report the continuous data as the mean ± standard deviation or median. We compared the continuous variables using Student’s t test or Mann-Whitney U test between the 2 groups. Categorical variables were summarized as the percentages and compared using the chi-square test. Pearson’s correlation coefficients examined the degree of association between examined variables. p Values <0.05 were considered significant. The receiver operating characteristics curve was used to demonstrate the sensitivity and specificity of the neutrophil/lymphocyte (N/L) ratio and the optimal cutoff value for predicting SEC in patients with MS. The effects of different variables on SEC were calculated using univariate analysis for each. The variables for which the unadjusted p value was <0.10 on logistic regression analysis were identified as potential risk markers and included in the full model. We reduced the model using backward elimination multivariate logistic regression analyses, and we eliminated potential risk markers using likelihood ratio tests. p Values <0.05 were considered significant, and the confidence interval (CI) was 95%. All statistical analyses were performed using the SPSS, version 15 (SPSS, Chicago, Illinois).
Results
A total of 62 consecutive patients were enrolled in the study. The patients were divided into 2 groups according to the presence of SEC. Of the 62 patients, 32 (mean age 45 ± 12 years; 75% women) were in SEC-negative group and 30 (mean age 45 ± 11 years; 63% women) were in the SEC-positive group. The baseline characteristics are listed in Table 1 . The mean age and gender of the patients were similar between the 2 groups (p = 0.875 and p = 0.319, respectively). No significant difference was found in the presence of hypertension, diabetes mellitus, smoking status, or previous coronary artery disease between the 2 groups ( Table 1 ). The incidence of previous cerebrovascular disease and a history of peripheral embolism was greater in the SEC-positive group; however, the difference did not reach significance (p = 0.312 and p = 0.516, respectively). However, the hs-CRP levels were significantly greater in the SEC-positive group than in the SEC-negative group (3.9 ± 2.2 vs 10.6 ± 6.3, p = 0.024).
| Variable | SEC | p Value | |
|---|---|---|---|
| No (n = 32) | Yes (n = 30) | ||
| Age (years) | 45 ± 12 | 45 ± 11 | 0.875 |
| Women | 24 (75%) | 19 (63%) | 0.319 |
| Hypertension | 16 (50%) | 12 (40%) | 0.429 |
| Diabetes mellitus | 9 (28%) | 8 (27%) | 0.898 |
| Smoke | 6 (19%) | 4 (13%) | 0.562 |
| Coronary artery disease | 10 (31%) | 6 (20%) | 0.312 |
| Cerebrovascular disease | 1 (3%) | 2 (7%) | 0.516 |
| Peripheral embolic events | 1 (3%) | 3 (10%) | 0.271 |
| High-sensitive C-reactive protein (mg/L) | 3.9 ± 2.2 | 10.6 ± 6.3 | 0.024 |
| Triglycerides (mg/dl) | 142 ± 33 | 138 ± 32 | 0.610 |
| Low-density lipoprotein (mg/dl) | 109 ± 22 | 111 ± 23 | 0.740 |
| High-density lipoprotein (mg/dl) | 36 ± 5 | 37 ± 6 | 0.763 |
| Total cholesterol (mg/dl) | 174 ± 23 | 175 ± 28 | 0.821 |
| Systolic blood pressure (mm Hg) | 120 ± 12 | 121 ± 14 | 0.586 |
| Diastolic blood pressure (mm Hg) | 77 ± 7 | 77 ± 5 | 0.588 |
| Heart rate (beats/min) | 81 ± 13 | 77 ± 12 | 0.214 |
| Body mass index (kg/m 2 ) | 22 ± 2 | 23 ± 2 | 0.394 |
| Atrial fibrillation | 11 (34%) | 16 (53%) | 0.132 |
| Aspirin | 16 (50%) | 17 (57%) | 0.599 |
| Warfarin | 12 (38%) | 15 (50%) | 0.321 |
With respect to the rhythm status of the patients, 34% and 53% of the patients in the SEC-negative group and the SEC-positive group were in atrial fibrillation, respectively (p = 0.132). Aspirin and warfarin use also were not significantly different between the 2 groups (p = 0.599 and p = 0.321, respectively).
The complete blood count parameters are listed in Table 2 . With respect to the white blood cell distribution, no significant difference was found in the eosinophil and monocyte count between the 2 groups (p = 0.887 and p = 0.207, respectively). However, the neutrophil levels (65 ± 9 vs 73 ± 9) were significantly greater in the SEC-positive group, and the lymphocyte levels (24 ± 7 vs 18 ± 6) were significantly greater in the SEC-negative group (p = 0.001 for each). The N/L ratio was also significantly greater in the SEC-positive group (3.0 ± 1.8 vs 4.5 ± 1.8, p = 0.003; Table 2 ). The receiver operating characteristics curve of N/L ratio for predicting SEC is shown in Figure 1 . A N/L ratio >3.1 mg/dl had a 80% sensitivity and 72% specificity in predicting SEC in patients with MS. Also, a significant correlation was detected between the hs-CRP level and the N/L ratio (r = 0.640; p <0.001; Figure 2 ).
| Variable | SEC | p Value | |
|---|---|---|---|
| No (n = 32) | Yes (n = 30) | ||
| Hemoglobin (g/dl) | 12.9 ± 1.9 | 13.2 ± 1.7 | 0.586 |
| Hematocrit (%) | 39.1 ± 5.0 | 39.7 ± 5.2 | 0.670 |
| Red blood cell distributed width (%) | 15.0 ± 2.7 | 14.7 ± 1.6 | 0.558 |
| Mean corpuscular volume (fl) | 87 ± 6 | 88 ± 7 | 0.428 |
| Platelet count (10 3 μL) | 258 ± 94 | 259 ± 67 | 0.976 |
| White blood cell distribution (%) | |||
| Lymphocytes | 24 ± 7 | 18 ± 6 | 0.001 |
| Neutrophils | 65 ± 9 | 73 ± 9 | 0.001 |
| Eosinophils | 2.3 ± 1.1 | 2.2 ± 1.3 | 0.887 |
| Monocytes | 8.9 ± 7.4 | 7.0 ± 3.7 | 0.207 |
| Neutrophil/lymphocyte ratio | 3.0 ± 1.8 | 4.5 ± 1.8 | 0.003 |
In the echocardiographic parameters, the left ventricular ejection fraction was not different between the 2 groups (p = 0.075). The mean gradient measured from the mitral valve, the systolic pulmonary arterial pressure, and right ventricle diameter were also not significantly different between the 2 groups ( Table 3 ). However, the left atrium volume was significantly greater in the SEC-positive group (73 ± 14 vs 68 ± 13, p = 0.03), and the planimetric mitral valve area was greater in the SEC-negative group than in the SEC-positive group (1.3 ± 0.3 vs 1.1 ± 0.2, p = 0.011; Table 3 ).
| Variable | SEC | p Value | |
|---|---|---|---|
| No (n = 32) | Yes (n = 30) | ||
| Left ventricular ejection fraction (%) | 63 ± 6 | 60 ± 7 | 0.075 |
| Mean gradient (mm Hg) | 11 ± 3 | 13 ± 5 | 0.107 |
| Mitral valve area (cm 2 ) | 1.3 ± 0.3 | 1.1 ± 0.2 | 0.011 |
| Left atrium volume (ml) | 68 ± 13 | 73 ± 14 | 0.030 |
| Systolic pulmonary arterial pressure (mm Hg) | 45 ± 8 | 47 ± 9 | 0.546 |
| Right ventricle diameter (cm) | 4.3 ± 1.1 | 4.4 ± 1.2 | 0.498 |
In the 2 groups, some of variables that can be effective on SEC were significantly different between the 2 groups. Thus, the effects of multiple variables on SEC were analyzed using univariate and multivariate logistic regression analyses. The variables for which the unadjusted p value was <0.10 on univariate analysis were identified as potential risk markers for SEC and included in the full model. On multivariate analysis, hs-CRP (odds ratio [OR] 1.235, 95% CI 1.040 to 1.466; p = 0.016), N/L ratio (OR 1.461, 95% CI 0.977 to 2.184; p = 0.02), mitral valve area (OR 0.135, 95% CI 0.020 to 0.503; p = 0.017), and left atrial volume (OR 3.012, 95% CI 1.501 to 5.611; p = 0.001) were independent risk factors of SEC in patients with MS ( Tables 4 and 5 ).
