Article, Cardiology

Transthoracic echocardiogram in syncope patients with normal initial evaluation

a b s t r a c t

Objectives: Despite the low diagnostic yield of echocardiogra0, it is often used in the evaluation of syncope. This study determined whether patients without abnormalities in the initial evaluation benefit from transthoracic echocardiogram and the clinical factors predicting an abnormal TTE.

Methods: This study enrolled 241 patients presenting to the emergency department with syncope. The TTE re- sults were analyzed based on risk factors suggesting cardiogenic syncope in the initial evaluation.

Results: Of the 115 patients with at least one risk factor, 97 underwent TTE and 27 (27.8%) had TTE abnormalities. In comparison, of the 126 patients without risk factors, 47 underwent TTE and only 1 (2.1%) had TTE abnormal- ities. Significantly different factors between patients with normal and abnormal TTE findings were entered in a multiple logistic regression analysis, which yielded age [adjusted odds ratio (aOR), 1.09; 95% CI, 1.02-1.15; p = 0.006], an abnormal electrocardiogram (ECG) (aOR, 7.44; 95% CI, 1.77-31.26; p = 0.010), and a brain natri- uretic peptide (BNP) level of N 100 pg/mL (aOR, 2.64; 95% CI, 1.21-5.73; p = 0.011) as independent predictors of TTE abnormalities. The cutoff value of age predicting an abnormal TTE was 59.0 years (area under the curve, 0.777; p b 0.001).

Conclusion: A patient who is older than 59 years or has an Abnormal ECG or an elevated BNP level may benefit from TTE. Otherwise, TTE should be deferred in patients with no risk factors in the initial evaluation.

(C) 2016

Introduction

Background

Syncope is one of the most common primary complaints seen in the emergency department (ED) and accounts for 1% to 3% of all ED visits [1, 2]. Yet a definite cause is identified in only 25% to 50% of affected pa- tients after the initial evaluation incorporating a meticulous history, physical examination, and electrocardiogram (ECG) [3,4].

When the initial workup is normal, establishing a definite cause of syncope is a major challenge to the physicians. The American Heart As- sociation/American College of Cardiology (AHA/ACC) states that an echocardiogram can be helpful when the history, physical examination, and ECG do not provide a diagnosis [5]. According to another report from the ACC, the use of echocardiogram as one of the diagnostic tool is appropriate when syncope patients have no previous disease [6]. Given the practical situation in which nearly half of patients remain un- diagnosed after the initial evaluation, an extensive workup including

* Corresponding author at: Department of Emergency Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Republic of Korea.

E-mail address: [email protected] (S.-W. Park).

echocardiogram appears to be needed. However the use of echocardio- gram can increase Medical costs and prolong ED length of stay. In addi- tion, there has been growing concern about low diagnostic yield of echocardiogram in patients with a normal initial evaluation [7-9].

Therefore, we performed this study to evaluate the diagnostic yield of echocardiogram in patients without abnormalities in the initial eval- uation and to identify the clinical variables readily available in the initial workup to predict an abnormal echocardiogram.

Methods

Patients

The eligible study population comprised consecutive patients (age >= 18 years) who presented to the ED of a tertiary university teaching hos- pital with syncope from November 2014 to October 2015. Syncope was defined as a sudden, transient of loss of consciousness with spontaneous recovery. Patients who complained of near-syncope (because of difficul- ty distinguishing syncope from dizziness) or had other definite causes of loss of consciousness, such as epilepsy, stroke, and alcohol or drug in- take, were excluded.

http://dx.doi.org/10.1016/j.ajem.2016.10.078

0735-6757/(C) 2016

282 S.-K. Han et al. / American Journal of Emergency Medicine 35 (2017) 281284

Clinical Outcome

We retrospectively reviewed the medical records of eligible patients to collect data on age, sex, underlying disease, history of prior syncope, prodromal symptoms, vital signs, and results of routine blood tests, ECGs, and transthoracic echocardiogram (TTE).

Two board-certified emergency physicians who were blinded to the patient information independently interpreted all ECGs obtained in the ED or during hospital admission. In case of disagreement between the two physicians, the findings were adopted by consensus. A patient was considered to have abnormal ECG findings when at least one of the following was present: Sinus bradycardia (heart rate b 50 beats per minute), arrhythmia (supraventricular tachycardia, atrial fibrillation/ flutter, pacing, or ventricular rhythm), premature beats, atrioventricular block (Mobitz type II second or third degree), left or Right bundle branch block, ventricular hypertrophy, ischemia related Q/ST/T changes, and an abnormal QT interval.

The TTE was performed by a cardiologist or sonographer and interpreted by a cardiologist. A patient was considered to have abnor- mal TTE findings when at least one of the following was present: mod- erate to severe regurgitation or stenosis of any valve, severe ventricular wall hypertrophy, an ejection fraction of b 45%, moderate to severe dia- stolic dysfunction, Hypertrophic cardiomyopathy with outflow tract ob- struction, severe pulmonary hypertension, regional Wall motion abnormality, and marked pericardial effusion.

The enrolled patients were classified into risk and no-risk groups based on the initial evaluation. The at-risk group had at least one of fol- lowing risk factors: (1) prodromal symptoms, including chest pain, chest discomfort, or palpitations; (2) history of arrhythmia, heart fail- ure, coronary artery disease, or structural heart disease; (3) laboratory findings of elevated cardiac enzymes (CK-MB) or brain natriuretic pep- tide (BNP); and (4) an abnormal ECG. The eligible patients were also classified into normal and abnormal TTE groups.

Statistical Analysis

The inter-rater reliability of the ECG interpretation was analyzed using kappa (?) statistics. Categorical variables are expressed as number (%), and between-group comparisons were made using the chi-square or Fisher’s exact test. Continuous variables are expressed as mean and standard deviation or median with the interquartile range (IQR). The normal and abNormal groups were compared using Student’s t-test or the Mann-Whitney U test. Significant variables were included in the multiple logistic regression analysis to identify independent risk factors predicting TTE abnormalities. The optimal cutoff value and ability of in- dependent variables to predict abnormal TTE results were assessed using the area under the Receiver operating characteristic curve . All statistical tests were performed using SPSS for Windows ver. 18.0 (IBM, Armonk, NY, USA) and MedCalc 7.4 (MedCalc Software, Mariakerke, Belgium). A p-value of b 0.05 was considered to indicate statistical significance.

Results

Baseline Characteristics of the Study Population and Initial Workup Results

The study population was 241 patients with a median age of 58.0 (range, 38.0-72.5). There was a progressive increase in the incidence of syncope after 40 years and a peak incidence at 70 to 80 years of age (Fig. 1). Fifty patients (20.7%) reported at least one recurrent attack of syncope. underlying diseases and prodromal symptoms that can be as- sociated with Cardiac syncope were observed in 39 (16.2%) and 21 (8.7%) patients, respectively. Fifty-nine (24.5%) patients had elevated troponin I, CK-MB, or BNP levels. ECG was performed in 235 patients and 90 (90/235, 38.3%) patients showed abnormal ECG findings. Of

Fig. 1. Incidence of syncope according to age.

the 241 patients in the study population, 115 patients (47.7) had at least one defined risk factor. The inter-rater agreement of the ECG inter- pretation between the two physicians was significant [? = 0.78; 95% confidence interval (CI), 0.68-0.87]. These results are summarized in Table 1.

TTE Results in the Risk and No-risk Group

The enrolled patients were classified into risk group (n = 115) and no-risk group (n = 126). Of the patients with risk factors, 97 underwent TTE, and abnormal TTE results were observed in 27 (27.8%). In compar- ison, TTE was performed in 47 patients in the no-risk group, and abnor- mal TTE results were observed in 1 (2.1%) patient (Table 2, Fig. 2).

Independent Factors Predicting Abnormal TTE Findings

The patients with abnormal TTE findings (n = 28) were significantly older (73.0 vs. 58.0 years, p b 0.001) and had a higher prevalence of un- derlying disease (82.1% vs. 60.3%, p b 0.001) than the patients with nor- mal TTE findings (n = 116). The hematocrit (p b 0.001) was lower and the troponin I (p = 0.004) and BNP levels (p b 0.001) were higher in the patients with abnormal TTE versus normal TTE findings. ECG abnormal- ities (p b 0.001) were also more frequent in the patients with abnormal TTE findings (Table 3). When these significant variables were entered into a multivariate logistic regression analysis with sex, we identified age [adjusted odds ratio (aOR), 1.09; 95% CI, 1.02-1.15; p = 0.006], an abnormal ECG (aOR, 7.44; 95% CI, 1.77-31.26; p = 0.010), and elevated

Table 1

Baseline characteristics and laboratory findings of 241 patients.

Characteristics Total (n = 241)

Male 124 (51.5)

Age (years) 58.0 (38.0-72.5)

Prior syncope, n (%) 50 (20.7)

Vital signs

Systolic blood pressure (mm Hg) 120 (100-140)

Heart rate (/minute) 77.6 +- 17.7

Patients with risk factor(s), n (%) 115 (47.7)

Underlying diseases, n 39

Arrhythmia/CAD/other heart diseasesa 13/21/7

Prodromal symptoms, n 21

Chest pain/palpitation/dyspnea 15/10/8

Laboratory findings, n 59

Elevated troponin I (N 0.05 ng/mL) 23/211

Elevated CK-MB (N 5.0 ug/L) 20/211 Elevated brain natriuretic peptide (N 100 pg/mL) 41/163 Electrocardiogram, n (abnormal/total) 90/235

Data are reported as number (%), mean +- standard deviation (SD) or median (interquar- tile range). CAD, coronary artery disease; CK-MB, creatine kinase-MB.

a Other heart diseases include heart failure, cardiomyopathy and pulmonary embolism.

S.-K. Han et al. / American Journal of Emergency Medicine 35 (2017) 281284 283

Table 2

Result of transthoracic echocardiography in patients with normal and abnormal

Table 3

Univariate analysis of factors associated with abnormal transthoracic echocardiogram.

electrocardiogram.

Characteristics

Abnormal

Normal TTE

p

Characteristics

Total

(n = 241)

Risk group (n = 115)

No-risk group (n = 115)

TTE

(n = 28)

(n = 116)

Performed echocardiogram, n

144

97

47

Male

15 (53.6)

57 (49.1)

0.674

Normal, n (%)

116 (80.6)

70 (72.2)

46 (97.9)

Age (years)

73.0

58.0

b0.001

Abnormal, n (%)

28 (19.4)

27 (27.8)

1 (2.1)

(64.0-78.0)

(41.5-72.0)

Underlying diseases

23 (82.1)

70 (60.3)

0.030

BNP levels (aOR, 2.64; 95% CI, 1.21-5.73; p = 0.011) as final risk factors associated with the TTE abnormalities (Table 4). The cutoff value of age predicting abnormal TTE was 59.0 years (AUROC, 0.777; sensitivity,

Diabetes mellitus

9

17

Hypertension

13

37

Arrhythmia

3

8

Coronary artery disease

8

9

Other heart diseasesa

4

8

Chronic kidney disease

2

3

Cerebrovascular accident

0

6

92.9%; specificity, 55.2%; p b 0.001).

Prior syncope

4 (14.3)

30 (25.9)

0.281

Prodromal symptoms

14 (50.0)

78 (67.2)

0.088

Discussion

Chest pain

3

6

Palpitation

1

4

Dyspnea

3

3

Othersb

9

54

Our study shows that patients with no abnormal findings in the ini- tial evaluation of syncope cannot benefit from TTE. Conversely, it is rea- sonable to perform TTE in patients older than 59 years or with an

abnormal ECG or Elevated BNP levels. This result may be informative

Vital signs

Systolic blood pressure (mm Hg) 130

(110-140)

110

(100-137.5)

0.080

for clinicians when deciding whether to perform TTE in patients pre- senting to the ED with syncope.

An ECG is used to detect heart disease. Several studies suggest that an ECG should be performed along with a meticulous history, physical examination in all patients presenting with syncope [5,10,11]. When abnormal ECG findings are observed, the echocardiogram is useful for further investigation. Conversely, is it reasonable to defer echocardio- gram unless the patient has a history of cardiac disease or abnormal ECG? The AHA/ACC guideline describes echocardiogram as a helpful screening test when the history, physical examination, and ECG do not provide a diagnosis [5]. However, several studies deny the benefit of the echocardiogram in unexplained syncope patients without clinical risk factors. Anderson et al. evaluated the 323 syncope patients who had no abnormal clinical factors such as unstable vital signs, new ECG changes, abnormal lab data and abnormal neurological exam. They found that 267 patients had a normal ECG and 235 of these underwent TTE; none had abnormal TTE findings [8]. In a study of Sarasin, 155 pa- tients with non-diagnostic initial evaluation underwent routine echo- cardiogram. This study showed that in patients with a negative history and normal ECG, echocardiogram was useless and detected only minor structural Cardiac abnormalities [9]. These results correspond to our finding that abnormal TTE findings were observed only 1 (2.1%) pa- tient with negative initial evaluation. Chiu et al. evaluated the diagnostic yield of Routine testing among the 570 patients presenting to the ED with syncope [12]. In this study, echocardiogram was performed in 150 (26%) patients and positive echocardiogram was 33 (22%). The rea- son why their diagnostic yield was higher compared to prior studies was that the echocardiogram was discriminately performed in the

Fig. 2. Segregation chart of enrolled patients. TTE, transthoracic echocardiogram.

Heart rate (/minute) 69.5 +- 21.8 79.0 +- 17.8 0.017 Laboratory findings

Hematocrit (%) 34.2 +- 7.1 38.4 +- 4.9 b0.001

Elevated troponin I (N 0.05 ng/mL) 10/28 (35.7) 13/105 (12.4) 0.004 Elevated CK-MB (N 5.0 ug/L) 7/28 (25.0) 13/104 (12.5) 0.102

Elevated brain natriuretic peptide (N 17/24 (70.8) 18/80 (22.5) b0.001 100 pg/mL)

Abnormal electrocardiogram 24 (85.7) 46 (43.6) b0.001

Data are reported as number (%), mean +- standard deviation (SD) or median (interquar- tile range). TTE, transthoracic echocardiogram; CK-MB, creatine kinase-MB; IVCD, intra- ventricular conduction disturbances.

a Other heart diseases include heart failure, cardiomyopathy and pulmonary embolism.

b Others include flushing, nausea, sweating, lightheadedness, dizziness, Blurred vision.

patients with increased illness severity. This was similar to the positive results (27.8%) in risk group of our study. Based on these findings, the use of echocardiogram should be restricted to the patients with positive initial workup.

Previous study reported that the incidence of syncope increased with age, had a steeper rise at the age of 70 years, and peaked at 80 years [13]. We observed a similar pattern, with a peak at 70 years. In terms of mortality, age is important because syncope in elderly pa- tients is related to a higher incidence of Cardiovascular causes and de- creased survival [14-16]. In our study, age was independent predictor of abnormal TTE, but the risk was not great (aOR, 1.09; 95% CI, 1.02-1.15); this may have been associated with the overall low rates of abnormal TTE findings in all age groups.

The hormone BNP is secreted by atrial and ventricular myocardial

cells in response to an increased ventricular volume [17,18]. The BNP level is not mentioned in the ESC or AHA/ACC syncope guidelines. How- ever, the plasma BNP level is reportedly useful in distinguishing cardiac from non-cardiac causes of syncope [19] and in risk stratification of pa- tients with syncope [20]. In our study, the odds ratio of an elevated BNP was relatively high (aOR, 2.64; 95% CI, 1.21-5.73). Given the strong cor- relation of BNP with left ventricular dimension, volume, ejection

Table 4 Multivariate analysis of independent risk factors of abnormal transthoracic echocardiogra- phy in syncope patients.

Characteristics

Adjusted OR (95% CI)

p

Age

1.09 (1.02-1.15)

0.006

Abnormal electrocardiogram

7.44 (1.77-31.26)

0.010

Elevated brain natriuretic peptide (N 100 pg/mL)

2.64 (1.21-5.73)

0.011

OR, odds ratio; CI, confidence interval.

284 S.-K. Han et al. / American Journal of Emergency Medicine 35 (2017) 281284

fraction, and Diastolic function, it seems reasonable to perform echocar- diography in patients with elevated BNP levels.

This study has several limitations. First it has a retrospective design and a relatively small number of patients. During the study period, there were no standard ED protocols for syncope evaluation. Clinical de- cision for evaluation methods were made largely by the residents caring for Patients with syncope. Thus, the TTE was performed without established indications, and no risk stratification was performed. BNP levels were also not measured in 78 (32.4%) patients and these omitted data might affect the results of this study. Furthermore, approximately half of patients with no abnormal findings in the initial evaluation did not undergo TTE in this study. Thus the diagnostic yield of TTE in these patients may be imprecise. In practice, however, there is difficulty performing TTE for a study in all patients without clinical risk factors by disregarding guidelines and the clinical features of each patient.

In conclusion, our study demonstrated that the use of echocardio- gram for syncope evaluation in patients older than 59 years or with el- evated BNP levels or an abnormal ECG is reasonable. However, echocardiogram should be deferred in patients with no risk factors in the initial evaluation.

Conflict of Interest

There is no potential conflict of interest related to this article.

References

  1. Sun BC, Emond JA, Camargo Jr CA. Characteristics and admission patterns of patients presenting with syncope to U.S. emergency departments, 1992-2000. Acad Emerg Med 2004;11:1029-34.
  2. Quinn JV, Stiell IG, Mcdermott DA, et al. Derivation of the San Francisco Syncope Rule to predict patients with Short-term serious outcomes. Ann Emerg Med 2004;43: 224-32.
  3. Crane SD. Risk stratification of patients with syncope in an accident and emergency department. Emerg Med J 2002;19:23-7.
  4. Croci F, Brignole M, Alboni P, et al. The application of a standardized strategy of evalua- tion in patients with syncope referred to three Syncope Units. Europace 2002;4:351-6.
  5. SA S, DW B, Biaggioni I, et al. AHA/ACCF Scientific Statement on the evaluation of syncope: from the American Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing, Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and Outcomes Research Interdisciplinary Working Group; and the American College of Cardiology Foundation: in collaboration with the Heart Rhythm Society: endorsed by the American Autonomic Society. Circulation 2006;113: 316-27.
  6. Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/ SCCT/SCMR 2011 appropriate use criteria for echocardiography. J Am Soc Echocardiogr 2011;24:229-67.
  7. Recchia D, Barzilai B. Echocardiography in the evaluation of patients with syncope. J Gen Intern Med 1995;10:649-55.
  8. Anderson KL, Alexaner L, et al. Cardiac evaluation for structural abnormalities may not be required in patients presenting with syncope and a normal ECG result in an observation unit setting. Ann Emerg Med 2012;60:478-84.
  9. Sarasin FP, Junod AF, Carballo D, et al. Role of echocardiography in the evaluation of syncope: a prospective study. Heart 2002;88:363-7.
  10. Linzer M, Yang EH, Estes 3rd NA, et al. Diagnosing syncope. Part 1: value of history, physical examination, and electrocardiography. Clinical efficacy assessment project of the American College of Physicians. Ann Intern Med 1997; 126:989-96.
  11. Huff JS, Decker WW, Quinn JV, et al. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope. Ann Emerg Med 2007;49:431-4.
  12. Chiu DT, Shapiro NI, Sun BC, Mottley JL, Grossman SA. Are echocardiography, telem- etry, ambulatory electrocardiography monitoring, and cardiac enzymes in emergen- cy department patients presenting with syncope useful tests? A preliminary investigation. J Emerg Med 2014;47:113-8.
  13. Ruwald MH, Hansen ML, Lamberts M, et al. The relation between age, sex, comorbid- ity, and pharmacotherapy and the risk of syncope: a Danish nationwide study. Europace 2012;14:1506-14.
  14. Del Rosso A, Alboni P, Brignole M, et al, Raviele A. Relation of clinical presentation of syncope to the age of patients. Am J Cardiol 2005;96:1431-5.
  15. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl

    J Med 2002;347:878-85.

    Getchell WS, Larsen GC, Morris CD, et al. Epidemiology of syncope in hospitalized patients. J Gen Intern Med 1999;14:677-87.

  16. Cheung BMY, Kumana CR. Natriuretic peptides: relevance in cardiac disease. JAMA 1998;280:1983-4.
  17. Maeda K, Takayoshi T, Wada A, et al. plasma brain natriuretic peptide as a biochem- ical marker of high left ventricular end-diastolic pressure in patients with symptom- atic left ventricular dysfunction. Am Heart J 1998;135:825-32.
  18. Tanimoto K, Yukiiri K, Mizushige K, et al. Usefulness of brain natriuretic peptide as a marker for separating cardiac and noncardiac causes of syncope. Am J Cardiol 2004; 93:228-30.
  19. Reed MJ, Newby DE, Coull AJ, et al. Role of Brain natriuretic peptide in risk stratification of adult syncope. Emerg Med J 2007;24:769-73.

Leave a Reply

Your email address will not be published. Required fields are marked *