Background
There are conflicting data on the incidence of ischemia by stress echocardiography in patients referred for dyspnea without accompanying chest pain.
Methods
A total of 311 consecutive patients with exertional dyspnea (without chest pain) referred to the echocardiography lab for ischemia evaluation from August 2008 to March 2012 were evaluated. Exercise by Bruce protocol or dobutamine stress echocardiography was performed. Resting left ventricular ejection fraction and segmental wall motion abnormalities were assessed. Multivariate logistic regression analysis was used to identify independent predictors of ischemia on stress echocardiography.
Results
The mean age was 61 years (range, 20–96 years), with 196 women (63%). Exercise stress was performed in 114 patients (37%); the rest of the patients underwent dobutamine stress. The patient population had a high burden of obesity, diastolic dysfunction, and pulmonary hypertension. Thirty patients (10%) had evidence of stress-induced ischemia (nine [8%] with exercise and 21 [11%] with dobutamine). In multivariate analysis, male gender (odds ratio, 2.8; P = .03), history of coronary artery disease (odds ratio, 3.5; P = .02), and resting wall motion abnormalities (odds ratio, 16.6; P < .01) were independent predictors of inducible ischemia.
Conclusions
The incidence of stress-induced ischemia is low in patients referred for stress echocardiography with exertional dyspnea (without chest pain). Ischemia is more likely to be present in men with histories of coronary artery disease and resting wall motion abnormalities.
Dyspnea is a subjective sensation that can be caused by a variety of clinical conditions, including pulmonary disease, obesity, anemia, and congestive heart failure. At the same time, ischemia in patients with coronary artery disease (CAD) can manifest without chest pain. Although nonspecific, dyspnea can be an angina equivalent in some patients. Previous studies have shown a wide range of stress-induced ischemia in patients referred for dyspnea without chest pain: from 19% (dobutamine echocardiography) to 42% (exercise echocardiography). Unlike other studies, the aim of the present study was to investigate the predictors of ischemia in an unselected, contemporary cohort of consecutive patients referred to stress echocardiography for exertional dyspnea without accompanying chest pain.
Methods
Study Population
An unselected cohort of 311 consecutive patients referred to St. Luke’s-Roosevelt Hospital Center in New York for stress echocardiography with exertional dyspnea without chest pain from August 2008 to March 2012 was included in the analysis. The study was approved by the hospital institutional review board.
Exercise Echocardiography
Exercise stress testing was offered to all patients without significant functional limitations. Maximal exercise treadmill testing was performed using the standard Bruce protocol. Reasons for termination were general fatigue, patient’s refusal to continue, severe angina, hemodynamically significant arrhythmias, ventricular tachycardia, or hemodynamic instability. Post-exercise echocardiographic images were acquired within 30 to 60 sec after the termination of treadmill exercise.
Dobutamine Stress Echocardiography
Dobutamine echocardiography was performed in patients with functional limitations who were unable to exercise (e.g., orthopedic problems), who had extremely limited exercise capacity, and who were unable to achieve target heart rates (defined as 85% of the maximal age-predicted heart rate) despite maximal effort. Dobutamine was administered intravenously beginning at doses of 5 to 10 μg/kg/min and increased by 10 μg/kg every 3 min to a maximum of 50 μg/kg/min or until a study end point was achieved. Atropine was administered intravenously in 0.25-mg increments every 3 min to a maximum of 2 mg if a study end point was not achieved at the maximum dobutamine dose.
The end points for termination of the dobutamine infusion included attainment of 85% of maximum age-predicted heart rate, inability to achieve 85% maximum age-predicted heart rate despite medications, the development of significant new segmental wall motion abnormalities (WMAs), the development of significant adverse effects related to the dobutamine infusion, and patient’s refusal to continue.
Cardiac rhythm was monitored throughout the stress echocardiography protocol, and 12-lead electrocardiograms and blood pressure measurements were obtained at baseline, at each level of stress, and during the recovery phase.
Echocardiographic Image Acquisition
During both types of stress echocardiography, transthoracic echocardiographic images were obtained with the patient in the left lateral decubitus position using commercially available ultrasound equipment (Acuson Sequoia, Siemens Medical Solutions USA, Inc., Mountain View, CA; GE Vivid 7 and 9, GE Healthcare, Wauwatosa, WI). Seven standard echocardiographic views were obtained with each acquisition: parasternal long-axis, parasternal short-axis, apical four-chamber, apical two-chamber, apical three-chamber, subcostal four-chamber, and subcostal short-axis views. Echocardiographic images were acquired at baseline (rest images), 5-μg to 10-μg dobutamine infusion (low-dose dobutamine images), and immediately after exercise or at peak dobutamine infusion (peak images). Valvular disease was coded if valvular dysfunction of at least moderate severity was present.
Echocardiographic Measurements and Image Analysis
Resting echocardiograms were read by an experienced echocardiographer, and chamber quantification was performed per American Society of Echocardiography guidelines. Left atrial volumes were estimated using Simpson’s rule. Septal e′ velocity and E/e′ ratio were used in the assessment of diastolic function. Pulmonary artery systolic pressure was estimated from the peak tricuspid regurgitation jet velocity with the addition of estimated right atrial pressure by inferior vena cava assessment. The left ventricle was divided into 16 segments as recommended by the American Society of Echocardiography, and a score was assigned to each segment at baseline, with each stage of stress (exercise or dobutamine), and during the recovery phase. Each segment was scored as follows: 1 = normal, 2 = mild to moderate hypokinesis (reduced wall thickening and excursion), 3 = severe hypokinesis (markedly reduced wall thickening and excursion), 4 = akinesis (no wall thickening and excursion), or 5 = dyskinesis (paradoxical wall motion away from the center of the left ventricle during systole).
A normal response to stress was defined as normal wall motion at rest with increases in wall thickening and excursion during stress. Myocardial ischemia was defined as (1) a left ventricular (LV) wall segment that did not increase in thickening and excursion during stress, (2) a deterioration in LV segment wall thickening and excursion during stress (increase in wall motion score of ≥1 grade), and (3) a biphasic response with dobutamine stress. Peak wall motion score index after stress was derived from the cumulative sum score of 16 LV wall segments divided by the number of visualized segments.
Statistical Analysis
Analysis was performed using a standard statistical package (SPSS for Windows version 16.0; SPSS, Inc., Chicago, IL). Patient groups were compared using Student’s t test for continuous variables and χ 2 or Fisher’s exact tests for categorical variables. The initial multivariate logistic regression model included important potential predictors of outcomes. Statistically significant univariate predictors of outcomes were included in the initial multivariate model, with care taken to avoid potential collinearity of predictors. The final parsimonious multivariate logistic regression model was created by a stepwise backward elimination strategy using goodness-of-fit assessment. P values < .05 were considered significant.
Results
Patient Characteristics
The study population consisted of 311 consecutive patients referred to the echocardiography lab by the treating physician for ischemia evaluation with exertional dyspnea without chest pain from August 2008 to March 2012. The average age of the cohort was 61 years, and unlike in other studies, ethnic minorities such as African Americans and Hispanics were prevalent, with Caucasians constituting 9% of the cohort. This reflects the patient population base served by our hospital center. Overall, 12% of patients had known CAD, and the population carried a significant burden of cardiovascular risk factors. These include hypertension (76%), diabetes mellitus (38%), hyperlipidemia requiring statin treatment (36%), and obesity (mean body mass index [BMI], 33.2 kg/m 2 ) ( Table 1 ). The average number of traditional cardiovascular risk factors, such as hypertension, hyperlipidemia, current smoking, and family history of early CAD, was 1.5 per patient.
| Characteristic | Overall ( n = 311) | Normal stress ( n = 281) | Abnormal stress ( n = 30) | P |
|---|---|---|---|---|
| Age (y) | 61.0 ± 13.1 | 60.9 ± 13.3 | 62.0 ± 11.3 | .67 |
| Race | ||||
| White | 28 (9%) | 26 (9%) | 2 (7%) | .71 |
| Black | 140 (45%) | 124 (44%) | 16 (53%) | |
| Hispanic | 138 (44%) | 126 (45%) | 12 (40%) | |
| Other | 5 (2%) | 5 (2%) | 0 | |
| Male gender | 115 (37%) | 99 (35%) | 16 (53%) | .05 |
| BMI (kg/m 2 ) | 33.2 ± 9.6 | 33.6 ± 9.8 | 29.5 ± 5.7 | .03 |
| Current smoking | 39 (13%) | 34 (12%) | 5 (17%) | .47 |
| Diabetes mellitus | 117 (38%) | 102 (36%) | 15 (50%) | .14 |
| Hypertension | 237 (76%) | 210 (75%) | 27 (90%) | .06 |
| Hyperlipidemia | 147 (47%) | 127 (45%) | 19 (63%) | .06 |
| Airway obstruction ∗ | 61 (20%) | 59 (21%) | 2 (7%) | .09 |
| Family history | 56 (18%) | 49 (17%) | 7 (23%) | .42 |
| History of CHF | 20 (6%) | 16 (6%) | 4 (13%) | .11 |
| Risk factors † | 1.5 ± 0.9 | 1.5 ± 0.9 | 1.9 ± 0.8 | .01 |
| Known CAD | 36 (12%) | 23 (8%) | 13 (43%) | <.01 |
| Prior CABG | 14 (5%) | 8 (3%) | 6 (20%) | <.01 |
| Prior PCI | 15 (5%) | 10 (4%) | 5 (17%) | <.01 |
| β-blockers | 86 (28%) | 71 (25%) | 15 (50%) | <.01 |
| ACE inhibitors/ARBs | 138 (44%) | 124 (44%) | 14 (47%) | .79 |
| Statins | 113 (36%) | 95 (34%) | 18 (60%) | <.01 |
| Diuretics | 90 (29%) | 80 (29%) | 10 (33%) | .58 |
| Nitrates | 11 (4%) | 8 (3%) | 3 (10%) | .08 |
∗ Asthma or chronic obstructive lung disease requiring inhaler therapy.
† Hypertension, hyperlipidemia, current smoking, and family history of early CAD.
Stress Echocardiography
Exercise stress was performed in 37% of patients; the rest of the patients underwent dobutamine stress ( Table 2 ). In general, a significant proportion of patients had markers of abnormal diastolic LV function, including left atrial dilation (57%), LV hypertrophy (LVH) (27%), and abnormal tissue Doppler findings (58%) on the resting study. Thirty-five percent of the patients had evidence of pulmonary hypertension, defined as estimated right ventricular systolic pressure > 35 mm Hg. Eight percent of the patients had regional WMAs at rest. During stress portion of the test, 10% of patients had new WMAs consistent with ischemia: nine (8%) with exercise and 21 (11%) with dobutamine.
| Characteristic | Overall ( n = 311) | Normal stress ( n = 281) | Abnormal stress ( n = 30) | P |
|---|---|---|---|---|
| Exercise | 114 (37%) | 105 (37%) | 9 (30%) | .43 |
| Resting SBP (mm Hg) | 136 ± 20 | 135 ± 20 | 144 ± 22 | .02 |
| Resting HR (beats/min) | 75 ± 15 | 75 ± 15 | 71 ± 12 | .13 |
| Peak SBP (mm Hg) | 154 ± 28 | 152 ± 26 | 167 ± 38 | <.01 |
| Peak HR (beats/min) | 145 ± 18 | 146 ± 19 | 144 ± 16 | .72 |
| Target HR achieved | 273 (88%) | 248 (88%) | 25 (83%) | .43 |
| QRS prolongation (>0.12 sec) | 21 (7%) | 18 (6%) | 3 (10%) | .44 |
| Ischemic ECG changes | 38 (12%) | 30 (11%) | 8 (27%) | .02 |
| LA dilation (volume index > 28 mL/m 2 ) | 177 (57%) | 153 (55%) | 24 (80%) | <.01 |
| E′ septal < 8 cm/sec | 179 (58%) | 156 (56%) | 23 (77%) | .03 |
| E/E′ septal > 15 | 57 (18%) | 48 (17%) | 9 (30%) | .08 |
| LVH | 84 (27%) | 71 (25%) | 13 (43%) | .03 |
| LVEF < 55% | 42 (14%) | 28 (10%) | 14 (47%) | <.01 |
| RVSP > 35 mm Hg | 108 (35%) | 92 (33%) | 16 (53%) | .02 |
| Valvular lesions | 50 (16%) | 41 (15%) | 9 (30%) | .04 |
| Resting WMAs | 25 (8%) | 11 (4%) | 14 (47%) | <.01 |
| Baseline wall motion score | 1.2 ± 0.5 | 1.1 ± 0.4 | 1.4 ± 0.7 | <.01 |
| Peak wall motion score | 1.2 ± 0.4 | 1.1 ± 0.4 | 1.6 ± 0.6 |
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