Article, Cardiology

Stress echocardiography in the ED: diagnostic performance in high-risk subgroups

a b s t r a c t

Purpose: To assess stress-echo (SE) diagnostic performance in patients presenting to the emergency department (ED) with spontaneous chest pain, especially in subgroups in which exercise ECG diagnostic performance has been questioned (women, elderly, history of coronary artery disease).

Methods: Between June 2008 and May 2011, 474 patients with an episode of spontaneous chest pain, non-diagnostic electrocardiogram and negative cardiac necrosis markers underwent SE. Patients with inducible ischemia (Isch) were asked to undergo coronary angiography. Patients with negative SE were discharged and contacted by telephone at least 6 months after discharge, to ascertain the occurrence of new cardiac events.

Main findings: Exercise stress-echo (ESE) was employed in 270 patients and dobutamine (DSE) in 218 (including 14 with inconclusive ESE); a diagnosis of coronary artery disease (CAD) was confirmed or excluded in 434 (92%) patients. SE was negative for Isch in 318 patients (206 ESE and 112 DSE) and positive in 132. During follow-up, patients with negative SE had 4 cardiac events. SE showed: sensitivity 90%, specificity 92%, positive predictive value 78% and negative predictive value 97%. Sensitivity was comparable between patients aged b or >= 70 years (84 vs 94%) and between gender (89 vs 96%), but lower in patients with known CAD (88 vs 94%, P b .05); specificity was comparable regardless of age (94 vs 99%) and presence of CAD (97 vs 91%), but was lower among women (87 vs 96%, P b .05).

Conclusions: SE had a very good diagnostic performance in ED patients with suspected Isch, both overall and in selected high-risk groups.

(C) 2013

Introduction

Patients presenting to the emergency department (ED) with spontaneous chest pain, non-diagnostic electrocardiogram (ECG) and negative cardiac necrosis markers still represent a challenge for the Emergency Physicians. Clinical variables have a very low specificity; nowadays, in order to minimize the risk of discharging patients with a false negative diagnosis, an early assessment with a provocative test, within 12 hours from ED presentation, is recommended [1]. Exercise ECG is the first choice test in patients with normal baseline ECG. However, its diagnostic performance is significantly reduced in patients with physical deconditioning, like elderly and obese patients; the test is often inaccurate also in other subgroups, such as women [2]. By using exercise ST-depression to define a positive test, the reported exercise ECG sensitivity and specificity for coronary disease diagnosis range between 23 and 100% (mean 68%) and 17 and 100% (mean 77%), respectively [2]. Considering the specific ED setting, several

* Corresponding author. High Dependency Observation Unit, Largo Brambilla 1, 50134 Firenze, Italy. Tel.: +39 055 7947748.

E-mail address: [email protected] (F. Innocenti).

papers demonstrated that stress echocardiography (SE) was more effective than exercise ECG in terms of risk stratification [3,4]; compared to exercise ECG, SE established a diagnosis of coronary artery disease (CAD) with less uncertainty and less cost. Exercise ECG may be inaccurate in other subgroups such as women and elderly patients [5,6].

Aim of the present study was to assess SE diagnostic performance in ED, both in the general population and in subgroups like women, known CAD patients and elderly patients, as they all represent subgroups where exercise ECG diagnostic performance has been questioned.

Methods

Study population

We retrospectively identified 474 consecutive unselected patients who underwent SE between June 2008 and May 2011 for CAD screening: all patients presented to ED with spontaneous chest pain, non diagnostic ECG and negative cardiac necrosis markers at the time of initial evaluation, after 6 and 12 hours. The second and third evaluations of the necrosis markers, as well as the SE, were performed in the Observation Unit. The first choice provocative test was exercise stress echo (ESE); nevertheless dobutamine was employed as stressor

0735-6757/$ – see front matter (C) 2013 http://dx.doi.org/10.1016/j.ajem.2013.05.006

Table 1

Clinical characteristics of the whole study population and according to presence of inducible ischemia

All

(n = 474)

SE+

(n = 132)

SE-

(n = 318)

P

Age (years)

67 +- 12

72 +- 10

65 +- 13

b.0001

Gender (male), n (%)

276 (58%)

77 (58%)

186 (58%)

NS

Hypertension, n (%)

296 (62%)

91 (69%)

187 (59%)

.044

Smoking, n (%)

108 (23%)

22 (17%)

79 (25%)

.002

Dyslipidemia, n (%)

192 (41%)

59 (45%)

122 (38%)

NS

Diabetes type 2, n (%)

71 (15%)

27 (20%)

39 (12%)

NS

Arterial vascular disease, n (%)

52 (11%)

28 (21%)

23 (7%)

b.0001

Known CAD, n (%)

119 (25%)

44 (33%)

68 (21%)

.008

Previous PCI, n (%)

101 (21%)

34 (26%)

61 (19%)

NS

Previous CABG, n (%)

Medications

20 (4%)

8 (6%)

12 (4%)

NS

?-Blocker, n (%)

126 (27%)

44 (33%)

76 (24%)

.039

ASA, n (%)

170 (36%)

65 (49%)

94 (30%)

.001

ACE inhibitor, n (%)

140 (30%)

43 (33%)

90 (28%)

NS

ARB, n (%)

92 (19%)

28 (21%)

56 (18%)

NS

Ca-antagonist, n (%)

67 (14%)

20 (15%)

41 (13%)

NS

Nitrate, n (%)

32 (7%)

17 (13%)

11 (4%)

b.0001

Renal failure, n (%)

12 (3%)

6 (5%)

5 (2%)

NS

Previous ictus or TIA, n (%)

23 (5%)

9 (7%)

10 (3%)

NS

Chest Pain Score

6 +- 3

7 +- 3

5 +- 3

b.0001

ARB, Angiotensin II Receptor Blockers; BMI, body mass index; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; ASA, acetylsalicylic acid; TIA, transient ischemic attack.

(DSE) in presence of reported exercise deconditioning, coexisting disease precluding the performance of maximal effort and left bundle- branch block on the ECG. At the moment of the test, main clinical data were collected, especially regarding pain characteristics, cardiovas- cular risk factors and previous cardiovascular disease.

Chest pain characteristics were encoded according to a modified Chest Pain Score [7], which takes into account the followings: pain characteristics (crushing, pressing, heaviness =3; sticking, pleuritic, pinprick =1), localization (substernal or precordial =3; epigastric, left chest, neck, lower jaw=1), radiation (as either arm, shoulder, back, neck, lower jaw =1; absence =0), associated symptoms (as dyspnea, nausea, diaphoresis =2; absence =0), recurrence in the

was estimated in metabolic equivalents (METs), using data from standard predicted equations.

Dobutamine stress protocols

?-Blocker therapy was not administered the day of the test. After baseline echocardiogram, the patients underwent DSE according to standard protocol [8]. Test end-points were achievement of 85%MPHR, positive ischemic response indicated by development of new asynergia in 2 or more adjacent myocardial segments, exces- sively increased (systolic blood pressure [SBP] N 240 mm Hg) or reduced (drop N 40 mm Hg from precedent phase, or SBP b 90 mmHg) blood pressure, repetitive ventricular or supraventricular ectopy, or ischemic ECG changes. If the test was positive for ischemia, metoprolol was infused in incremental doses of 0.5 mg, until symptoms or ECG and echocardiographic modifications resolved.

Echocardiographic analysis

Left ventricular (LV) end-diastolic and end-systolic volumes were calculated by Simpson rule; all values were indexed by body surface area. At baseline, at peak stress and after recovery, digitized images, from parasternal long- and short-axis and apical 4- and 2-chamber views were stored on disk, to allow quad-screen visualization. LV regional wall motion was assessed according to the recommendations of the American Society of Echocardiography, based on a 16-segments model in which each segment was scored 0=not visualized, 1= normokinetic, 2=hypokinetic, 3=akinetic, 4=dyskinetic, or 5= aneurysm. Wall Motion Score Index (WMSI) was calculated at baseline and peak stress as the ratio between the cumulative sum score and the number of visualized segments. Inducible ischemia was defined as the development, in at least two adjacent segments, of new asynergia or biphasic response (basal asynergia improving at low dose

Table 2

Baseline and stress echocardiographic parameters of the whole study population and according to presence of inducible ischemia

previous 7 days (yes =3, no =0).

All patients gave their informed consent and the study is

consistent with the principles of the Declaration of Helsinki of clinical

EF (%)

58 +- 13

54 +- 13

60 +- 12

.002

research involving human patients.

LVDVI (mL/m2)

LVSVI (mL/m2)

50 +- 15

23 +- 13

54 +- 14

26 +- 13

49 +- 15

21 +- 13

.010

.011

2.2. exercise stress test protocol

LV Mass

86 +- 26

94 +- 28

83 +- 25

.001

Baseline WMSI

1.25 +- 0.44

1.38 +- 0.50

1.20 +- 0.42

b.0001

The ESE was performed according to the standard Bruce protocol,

Peak WMSI

1.32 +- 0.47

1.70 +- 0.46

1.18 +- 0.40

b.0001

aiming at reaching at least the 85% of the age-adjusted maximal predicted heart rate (%MPHR: [220 – age in years] x0.85); the test

METs at peak Stressor

Dobutamine (%)

6.3 +- 1.5

218/488a (45%)

5.8 +- 1.4

91/218 (42%)

6.4 +- 1.5

112/218 (51%)

.015

b.0001

All patients (n = 474)

SE+

(n = 132)

SE- P

(n = 318)

Index (g/m2)

was considered positive if angina or angina-equivalent symptoms

Exercise (%) 270/488 (55%) 41/270 (15%) 209/270 (77%)

were induced by the exercise and/or >=1 mm ST-segment depression measured at 80 milliseconds after J point developed at peak stress or during recovery. Before, and immediately after exercise completion, echocardiographic images (iE33; Philips Medical System, Andover, MA) in the parasternal long and short axis and apical 4 and 2 chambers view were acquired to allow quad-screen visualization. With evidence of new or worsening wall motion abnormalities at post-stress examination, the test was considered positive, regardless the presence of symptoms or ECG changes.

The ESE was considered inconclusive for inability to reach 85%MPHR, in absence of ECG and echocardiographic changes. The test was prematurely terminated in the presence of angina, ischemic ST-segment depression N 2 mm, significant ventricular ectopy, systolic blood pressure N 250 mmHg or excessive blood pressure decrease during exercise. The test was considered normal if

Baseline HR in ESE (bpm) Baseline HR in DSE (bpm)

Peak HR in ESE (bpm)

Peak HR in DSE (bpm)

Baseline SBP in ESE (mmHg) Baseline SBP in DSE (mmHg)

Peak SBP in ESE (mmHg)

Peak SBP in DSE (mmHg)

Atropine during DSE, n (%)

77 +- 15 75 +- 15 78 +- 14 NS

68 +- 11 66 +- 11 70 +- 11 .024

145 +- 19 137 +- 20 147 +- 18 .005

122 +- 16 116 +- 18 129 +- 12 .001

127 +- 16 130 +- 17 127 +- 15 NS

130 +- 18 128 +- 18 130 +- 18 NS

177 +- 25 176 +- 26 178 +- 25 NS

132 +- 28 129 +- 30 134 +- 26 NS

89/218 (41%) 32/91 (35%) 48/112 (43%) NS

85%MPHR was reached without symptoms, ECG and echocardio- graphic abnormalities. Peak exercise capacity from the treadmill test

EF, ejection fraction; HR, heart rate.

a Including 14 patients who performed also an ESE.

follow-up data“>100

75

50

(%)

25

0

Fig. 1. SE overall diagnostic performance.

%MPHR for physical deconditioning. One only female patient reported typical chest pain and ECG abnormalities without new wall motion asynergy; the test was considered positive and the patient underwent coronary angiography that did not show any critical coronary stenoses. Twelve of the 20 patients with non-diagnostic ESE under- went DSE: 11 patients reached a conclusive result (9 negative and 2 positive) and one patient remained with an inconclusive result. Also 2 patients with negative ESE underwent DSE: 1 was negative and 1 was positive for inducible ischemia.

Dobutamine stress-echocardiography was performed in 218 patients, including those who had already performed an ESE (12 with non-diagnostic and 2 with negative ESE): DSE showed inducible ischemia in 72 patients and it was negative in 112. In 15 patients the test was non-diagnostic and in 19 it was interrupted for adverse reactions (the most common was a significant decrease in blood pressure), never severe and quickly resolved with infu- sion interruption and administration of metoprolol. ESE allowed to confirm or exclude the presence of inducible ischemia in a

and worsening at high dose Dobutamine infusion). When 2 or more

segments were not visualized, both at baseline and at peak stress, the echocardiographic exam was considered suboptimal.

Coronary angiography

Selective coronary angiography was performed from the femoral or radial approach, in multiple views, using Judkin’s technique. Significant coronary disease was defined as N 50% luminal diameter stenoses in any of the major coronary branches.

Follow-up data

Data about coronary angiographies performed by patients with positive SE were collected from medical records, in order to verify the presence of Significant coronary lesions. All patients with a negative SE were contacted by telephone to verify the occurrence of new major events (cardiac death, non-fatal acute coronary syndrome, acute coronary syndrome [ACS], revascularization procedures). Telephone calls were made 1 month after the test; between December 2011 and January 2012 calls were repeated to collect follow-up information at least 6 months after the test.

Statistical analysis

Data were analyzed with SPSS program (SPSS Inc, Chicago, IL). Parametric data were reported as mean +- SD. The comparison between the 2 groups was made with Student t test for non-coupled parametric data. Non parametric data were analyzed with Fisher exact test.

SE sensitivity, specificity, and positive and negative predictive value (PPV and NPV) were calculated according to standard formulas; comparison of these parameters between groups was made with Fisher exact test. P b .05 was considered significant.

Results

Clinical and echocardiographic characteristics of our patients, in the whole group and according to presence of inducible ischemia, are listed in Tables 1 and 2. At baseline, the quality of the echocardio- graphic exam was suboptimal in 11 (2%) patients; at peak stress, in 10 more patients two or more segments were not correctly visualized.

Eco-stress results

Exercise stress echocardiography was performed in 270 patients and it showed inducible ischemia in 41 patients. ESE was negative in 208 and non-diagnostic in 20 patients due to the inability to reach

higher proportion of patients than DSE (250 or 93% vs 184 or 84%, P = .005); in the whole group, a diagnosis of CAD was confirmed or excluded in 434 (92%) patients. When considering negative and positive tests separately, ESE exhibited a higher proportion of negative tests (206 or 76% ESE vs 112 or 51% DSE, P b .0001) and a lower proportion of positive tests (41 or 15% ESE vs 91 or 42% DSE, P b .0001) than DSE.

Patients who underwent DSE were older (74+-9 vs 61 +- 9 years, P b

.0001), with higher LV end-diastolic and end-systolic volume indices (LV end-diastolic volume index [LVDVI] 52 +- 18 vs 51 +- 13 mL/m2, P =.039; LV end-systolic volume index [LVSVI] 26 +- 17 vs 22 +- 10 mL/m2, P b .0001) and worst LV global systolic function, both in terms of ejection fraction (EF, 53 +- 14 vs 60 +- 11%, P = .001) and segmental

kinesis (baseline WMSI: 1.36 +- 0.51 vs 1.19 +- 0.37, P b .0001).

Patients with a positive test for inducible ischemia (Table 1) were significantly older, more frequently affected by hypertension, arterial vascular disease and a known CAD than patients with negative test. Chest Pain Score was significantly higher in patients with positive test than patients with negative SE, suggesting that a typical chest pain is a strong predictor of a positive SE.

Follow-up

Among 113 patients with inducible ischemia, 98 (87%) underwent coronary angiography (mean latency 2 +- 3 days), while 15 subjects refused the exam; 2 patients with known CAD and inconclusive SE and 4 patients without evidence of ischemia performed coronary angiography. The coronary angiography showed the presence of significant coronary artery disease in 80 cases, including 2 patients with negative SE for inducible ischemia; 37 patients underwent an early percutaneous coronary revascularization and 3 within 6 months. During the follow-up (mean length 679 +- 299 days) 76 patients were lost; therefore, 398 patients were contacted, 113 (30%) with a positive test for inducible ischemia, 266 (70%) with a negative test and

19 (5%) with an inconclusive test. Patients lost to follow-up demonstrated a similar prevalence of test results, respectively, 27, 73, and 10% (P = NS). During follow-up, 12 more patients underwent coronary angiography, according to treating physician’s opinion: 6 patients had inducible ischemia during SE, 5 had a negative test, and 1

Table 3

ESE and DSE diagnostic accuracy

ESE

DSE

P

Sensitivity (95% CI)

88 (71%-96%)

90% (77%-97%)

NS

Specificity (95% CI)

98 (95%-100%)

83% (75%-90%)

b.0001

PPV (95% CI)

90% (74%-98%)

70% (57%-81%)

NS

NPV (95% CI)

98 (94%-99%)

95 (88%-98%)

NS

Table 4

Baseline and stress echocardiographic parameters by age, gender, and presence of known CAD in patients with follow-up

Age <=70 (n = 224)

Age N 70 (n = 174)

P

Male

(n = 220)

Female

(n = 178)

P

CAD

(n = 111)

No CAD (n = 287)

P

Hypertension (%)

115 (51%)

135 (78%)

b.0001

121 (55%)

129 (72%)

b.0001

77 (69%)

173 (60%)

NS

Dyslipidemia (%)

101 (45%)

60 (34%)

.032

87 (40%)

74 (42%)

NS

71 (64%)

90 (31%)

b.0001

Smoking habitus (%)

124 (55%)

62 (36%)

b.0001

139 (63%)

47 (26%)

b.0001

77 (69%)

109 (38%)

b.0001

Peripheral arterial disease (%)

17 (8%)

23 (13%)

NS

31 (14%)

9 (5%)

.003

17 (15%)

23 (8%)

.030

Chest Pain Score

6.0 +- 3.1

5.5 +- 3.7

NS

5.5 +- 3.1

6.1 +- 3.5

NS

6.1 +- 3.3

5.7 +- 3.3

NS

Medications

ASA

63 (28%)

72 (41%)

.006

79 (36%)

56 (31%)

NS

77 (69%)

58 (20%)

b.0001

Nitrates

8 (4%)

19 (11%)

.004

15 (7%)

12 (7%)

NS

19 (17%)

8 (3%)

b.0001

ACE-inhibitors

57 (25%)

60 (34%)

NS

68 (31%)

49 (28%)

NS

53 (48%)

64 (22%)

b.0001

?-Blockers

54 (24%)

48 (28%)

NS

57 (26%)

45 (25%)

NS

54 (49%)

48 (17%)

b.0001

LVDVI (mL/m2)

50 +- 14

50 +- 16

NS

54 +- 14

42 +- 12

b.0001

56 +- 17

47 +- 13

.002

LVSVI (mL/m2)

22 +- 13

23 +- 13

NS

24 +- 13

17 +- 10

b.0001

29 +- 16

19 +- 8

b.0001

EF (%)

60 +- 12

56 +- 13

.017

57 +- 12

61 +- 12

NS

52 +- 14

62 +- 10

b.0001

LV mass index (g/m2)

80 +- 23

94 +- 29

b.0001

89 +- 25

80 +- 27

.005

91 +- 28

83 +- 25

.015

Baseline WMSI

1.18 +- 0.38

1.34 +- 0.50

b.0001

1.29 +- 0.47

1.16 +- 0.34

.002

1.57 +- 1.52

1.10 +- 0.28

b.0001

Peak WMSI

1.25 +- 0.42

1.42 +- 0.52

b.0001

1.38 +- 0.51

1.21 +- 0.37

b.0001

1.68 +- 1.55

1.16 +- 0.32

b.0001

METs at peak

6.6 +- 1.4

5.4 +- 1.2

b.0001

6.7 +- 1.4

5.6 +- 1.4

b.0001

6.2 +- 1.2

6.6 +- 3.1

NS

Peak HR in ESE (bpm)

149 +- 17

132 +- 18

b.0001

145 +- 18

143 +- 19

NS

134 +- 14

147 +- 18

b.0001

Peak HR in DSE (bpm)

125 +- 19

121 +- 15

NS

118 +- 17

123 +- 16

.049

118 +- 14

123 +- 18

NS

Adverse reactions

.004

.036

NS

Hypotension, n (%)

8 (4%)

11 (6%)

7 (3%)

16 (9%)

2 (2%)

17 (6%)

Ventricular arrhythmias (%)

3 (2%)

10 (6%)

14 (6%)

4 (2%)

7 (7%)

6 (2%)

SV arrhythmias (%)

2 (1%)

10 (6%)

6 (3%)

6 (3%)

4 (4%)

8 (3%)

No adverse reactions

165 (74%)

123 (71%)

185 (84%)

140 (79%)

85 (77%)

203 (71%)

EF, ejection fraction; HR, heart rate; SV, supraventricular.

an inconclusive SE. Significant coronary lesions were present in 6 patients, 3 with and 3 without inducible ischemia. Moreover, during the follow-up 6 ACS were observed: 1 patient had an ACS 1 month after a positive SE and died in 1 week. Another patient with negative SE died of ACS 1 year later. Three more patients with a negative SE experienced an ACS. Moreover, 1 ACS occurred in a patient with non- conclusive test and 1 cardiac death occurred in a patient with inducible ischemia who refused coronary angiography. In conclusion, in patients with a negative test cumulative incidence of hard cardiac events was 1.5% (4/266 patients).

The diagnostic performance of stress-echo was evaluated in our population on the basis of the angiographic results and follow-up data; inconclusive tests were excluded from this analysis. The SE showed a sensitivity of 90% (95% confidence interval [CI], 0.819- 0.953), a specificity of 92% (95% CI, 0.880-0.947), a PPV of 78% (95% CI,

0.687-0.854), and an NPV of 97% (95% CI, 0.937-0.984) (Fig. 1). As

reported in Table 3, ESE showed a better specificity than DSE.

SE diagnostic performance in elderly patients

Because in the whole group the median age was 69 years, we subdivided the entire population in 2 groups: patients aged N 70 years (n = 174) and younger patients (n = 224). Female gender (58 vs 35%, P b .0001) and known CAD prevalence (33 vs 24%, P = .033) were higher among older patients. Clinical and echocardiographic characteristics according to age groups are shown in Table 4. Pharmacological stress was employed more frequently among the elderly (74 vs 25%, P b .0001); in this group, patients who performed an ESE reached a significantly lower workload. Elderly patients developed more frequently inducible ischemia (41 vs 20%, P b

.0001), while non diagnostic tests were equally distributed between the 2 groups (6 vs 9%, P = NS). During follow-up, three cardiac events occurred in the elderly: 2 ACS in patients with negative SE and one death in a patient with a positive SE. Among younger patients, 2 ACS developed in patients with negative SE, in one case followed by death, and 1 ACS developed in a patient with positive SE, early complicated by death.

Analysis of SE diagnostic performance showed a comparable performance regardless of age (Fig. 2, A).

SE diagnostic performance according to gender

Our study group included 220 male and 178 female patients. Women were older than men (71 +- 10 vs 64 +- 13 years, P b .0001) but they had less frequently a history of CAD (19 vs 35%, P b .0001); clinical and echocardiographic data according to gender are shown in Table 4. Dobutamine was employed more frequently in women than in man (64 vs 33%, P b .0001); among all the patients undergoing ESE, women reached a lower work load. Overall prevalence of non conclusive tests was similar in the two subgroups (5% in men and 9% in women, p = NS) and inducible ischemia developed in a similar proportion of patients (30% in both subgroups). During follow-up, cardiac events occurred in 1 woman and in 5 men (p = NS). In conclusion, SE in women was significantly less specific than in men, with a lower PPV and a similar high NPV (Fig. 2, B).

SE diagnostic performance according to presence of known CAD

We compared SE diagnostic performance between patients with known (n = 111) and suspected CAD (n = 287). Patients with known CAD were older (70 +- 11 vs 66 +- 13 years, P = .002), with a higher prevalence of male gender (72 vs 53%, P <= .0001). Clinical and echocardiographic characteristics according to the presence of known CAD are shown in Table 4.

In patients with known CAD, dobutamine was the most employed stressor (56 vs 43%, P = .02) and inducible ischemia developed in a higher proportion of patients (41 vs 26%, P = .004). During follow-up, patients with known CAD reported 3 ACS, in one case followed by death, all in absence of inducible ischemia during SE. Cumulative incidence of cardiac events in patients with negative SE was respectively 3/61 (5%) in known CAD and 1/225 (0.4%) in non-CAD patients (P = .03). SE showed a significantly higher PPV and lower NPV in patients with a history of CAD than in patients with suspected CAD (Fig. 2, C).

Discussion

In this study we demonstrated that SE, both pharmacological and physical, was highly feasible and showed an optimal diagnostic performance in an ED setting; test performances were very good also

100

84%

94%

50

(%)

0

100

89%

96%

50

(%)

0

100

50

(%)

0

*P < .05

Aged <70 yrs

Aged >70 yrs

94%

89%

76%

80%

96%

97%

Male sex Female sex

*

*

96%

87%

91%

58%

95%

99%

Known CAD Suspected CAD

*

*

Diagnostic performance in special subgroups

We chose the aforementioned subgroups because they represent population at higher risk, especially known CAD patients and Elderly people. Regarding diagnostic assessment of patients presenting to ED with chest pain, the Scientific Statement of American Heart Associ- ation recommended evaluating these subgroups by an imaging modality, in order to reduce false negative tests [1].

Availability of a pharmacological stressor, well tolerated by almost all patients, made the test highly feasible and accurate among elderly patients, who are often unable to perform a diagnostic exercise ECG for physical deconditioning or coexisting disease [12]. Elderly patients represent a significant proportion of patients presenting to ED with spontaneous chest pain and in this clinical setting SE showed an optimal diagnostic performance and a very high NPV.

A

The non-invasive diagnosis of CAD in women is challenging because of a gender-related reduced sensitivity, especially of exercise ECG. A recent meta-analysis involving a large population demon- strated a similar sensitivity and specificity for SE between the 2 genders, together with a better specificity compared to stress nuclear imaging [13]. In our study population, SE showed lower specificity and PPV, but a very high NPV and comparable performance among women versus men. We did not observe the previously reported lower sensitivity [14]; the authors attributed this finding to the lower dobutamine dose necessary to obtain the desired heart rate increase, with a consequent lower increase in oxygen consumption and false negative test. In a setting like ED, our results are of outmost importance because they allows ED physicians to be reasonably safe in discharging women with a negative test for inducible ischemia.

B

Among patients presenting to the ED with spontaneous chest pain, known CAD patients are the subgroup with the highest proportion of missed diagnosis and hard cardiac events at follow-up [15]: in this subgroup, SE demonstrated an excellent diagnostic performance, but a significant lower NPV compared to patients without a history of CAD. Although cumulative incidence of new hard cardiac events among patients with a negative SE was very low, it was significantly higher among known CAD patients; this is why they require a special attention also in absence of signs of inducible ischemia.

The retrospective design of this study and the high number of patients lost at follow-up represent significant limitations. As in previous works, we assumed that the absence of cardiac events in the first months after the SE was the confirmation of a true negative exam: although we can’t exclude the presence of non critical lesions undetected by the SE, the very low incidence of new cardiac events at follow-up confirms that our assumption was correct in a very high proportion of patients. Another limitation was the low number of new events during follow-up: even though it represents per se an optimal result, precludes the possibility of a meaningful analysis of predictors of a bad prognosis.

C

88%

94%

97%

91%

95%

69%

92%

99%

Fig. 2. Diagnostic performance of SE in elderly patients (A), women (B) and patients with a history of CAD (C).

in specific subgroups where they have been questioned. Cumulative incidence of hard cardiac events among patients with a negative SE was very low, even in high risk subgroups, such as patients with a history of CAD. NPV was high in all subgroups; our results therefore confirmed the good applicability of SE in an environment like ED, where one of the most important requirements is to avoid inadvertent discharge of patients with an ACS, with obvious morbidity and mortality consequences. Our data confirm previous reports, which found a good diagnostic and prognostic performance for SE [7,9-11]. Compared to previous papers, our study population was one of the largest and, to the best of our knowledge, it was the first to examine diagnostic performance in ED setting in special subgroups, such as women, elderly people and patients with known CAD.

In conclusion, SE represents a feasible tool for Screening patients

presenting to ED with spontaneous chest pain; given the very high NPV, a negative test allows the ED physicians to early discharge these patients. Our results supported this disposition both for the general population and for special subgroups, as women, elderly people and patients with a previous history of CAD.

References

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