Exercise echocardiography

Antonello 2005 (Exercise stress echocardiography)

Participants: A total of 607 patients were included in the study.

The initial cohort included 640 consecutive patients who underwent exercise echocardiography clinically indicated from July 1997 to December 2003 for the evaluation of chest pain symptoms or for cardiac risk stratification. 22 patients who underwent coronary artery revascularisation within 3 months of ESE procedure, and 8 patients who were lost to follow-up (0.9%), were censored. Non cardiac death occurred in 3 patients: 2 for malignant cancer and 1 for a car accident.

The baseline characteristics of the sample were as follows: age (years): 58.5±10.9; males: 470 (77.4%); family history of CAD: 455 (75.8%); diabetes mellitus: 91 (14.9%); hypercholesterolemia: 361 (59.4%); arterial hypertension: 394 (64.9%); smokers: 355 (58.4%); angina: 520 (85.6%); previous AMI: 260 (42.8%); previous PTCA 61 (10.1%).

Exercise echo was performed for the diagnosis of suspected CAD in 267 patients (43.9%) and for risk stratification of known CAD in 340 patients (56.1%). Medical treatment if present was discontinued 3 days before the test.

Tests: Exercise stress echocardiography (ESE) was performed by bicycle ergometer in a supine position, using a standard Bruce protocol.

Echocardiographic analysis: All examinations were reviewed by 2 independent observers. For LV motion analysis, standard 16 segment LV model of the American Society of Echocardiography was used, and wall motion was scored as 1=normal; 2=hypo kinetic; 3=akinetic; 4= dyskinetic. LV wall motion score index (WMSI) was calculated a t baseline and at peak effort dividing the sum of individual segment scores by the number considered segments.

Outcomes: The primary outcomes were cardiac death, and cardiac death and non fatal MI.

Follow-up: Patients follow-up assessed for a mean period of 46.9 months (range 12–60 months).

Statistical analysis: Independent predictors of cardiac events (cardiac death, cardiac death+MI) were identified by univariate and multivariate Cox proportional hazard regression models. The 0.05 probability level was adopted for significant association between predictive variables and events. The risk associated with a given variable was expressed by a hazard ratio with a corresponding 95% CI. At multivariate analysis an automatic backward stepwise procedure was adopted.

Results: Cardiac events

During the follow-up there 48 deaths (21.6%) and 34 acute non fatal MIs (15.3%).

Univariate predictive value of clinical risk factors and Exercise stress echocardiography (ESE) results for cardiac events

Table XUnivariate predictive value of clinical risk factors and Exercise stress echocardiography (ESE) results for cardiac death

Risk factors:hazard ratio (95% CI)p value
Clinical data
Age:1.9 (1.5 to 4.8)<0.01
Hypercholesterolemia:1.3 (0.7 to 4.4)ns
Cigarette smoking:4.1 (2.3 to 4.8)<0.001
Rest echocardiographic data
Rest WMSI (wall motion score index) :3.6 (2.3 to 6.1)<0.01
ESE data
Positive ESE:5.1 (4.8 to 5.8)<0.0001
Peak WMSI (wall motion score index):4.8 (4.2 to 5.7)<0.0001
Low workload;4.1 (3.5 to 5.1)<0.001
Angina during ESE:2.2 (1.9 to 3.6)NS

Table XUnivariate predictive value of clinical risk factors and Exercise stress echocardiography (ESE) results for cardiac death or MI

Risk factors:hazard ratio (95% CI)p value
Clinical data
Age:1.2 (1.1 to 5.2)ns
Hypercholesterolemia:4.7 (3.3 to 6.0)<0.001
Cigarette smoking:1.3 (1.2 to 4.6)ns
Rest echocardiographic data
Rest WMSI (wall motion score index)3.8 (2.4 to 5.8)< 0.01
ESE data
Positive ESE:5.3 (4.9 to 5.6)<0.0001
Peak WMSI (wall motion score index):5.0 (4.8 to 6.1)<0.0001
Low workload:2.3 (1.4 to 4)ns
Angina during ESE:4.1 (2.8 to 4.9)<0.001

Table XMultivariate predictive value of clinical risk factors and Exercise stress echocardiography (ESE) results for cardiac death

VariablesChi square (χ2)p valuevariables selected (partial χ2; 95% CI; p)
Clinical9.30.01cigarette smoking (2.8; 1.8 to 4.1; <0.01)
Clinical +rest echo11.80.001rest WMSI (3.0; 2.1 to 4.1 ;< 0.01)
Clinical +rest echo+ ESE:37.90.00001positive ESE (4.1; 3.6 to 4.4; <0.0001)
Peak WMSI (3.5; 2.8 to 4.1); <0.0001
Low workload (3.1; 2.7 to 3.7; <0.01)

Table XMultivariate predictive value of clinical risk factors and Exercise stress echocardiography (ESE) results for cardiac death+MI

Variables:Chi-square (χ2 )p valuevariables selected (partial χ2; 95% CI; p)
Clinical9.60.01hypercholesterolemia (2.5; 1.6 to 3.3; <0.01)
Clinical +rest echo12.50.001rest WMSI (3.1; 2.4 to 3.8 ;< 0.01)
Clinical +rest echo+ ESE39.60.00001Positive ESE (4.5; 3.6 to 5.3 ;< 0.0001)
Peak WMSI (3.7 ; 2.6 to 4.4; <0.0001)
Angina during ESE (2.9; 2.3 to 3.8; <0.01)

Summary: At univariate analysis, the following variables were significant predictors of cardiac death (in descending order): ESE positive for ischaemia, peak WMSI, low workload, rest WMSI, cigarette smoking and age. Multivariate analysis identified ESE positive for ischaemia, peak WMSI, low workload and cigarette smoking as strongest independent predictors of cardiac death. The global Chi-square2 )of this combined clinical and stress test model was 37.9 (p<0.00001). For cardiac death+MI, the following variables were significant univariate predictors: positive stress test, peak WMSI, angina during the test, rest WMSI, hypercholesterolemia and cigarette smoking. However, multivariate analysis identified positive ESE, peak WMSI, angina during the test and hypercholesterolemia as the only independent determinants of cardiac death or MI. The global χ2 of this combined clinical and stress test model was 39.8 (p<00001). The results emphasise that information obtained by ESE is additional and independent to that provided by clinical and rest echocardiographic data.

Strengths: The study sample represented the population of interest with regard to key characteristics. Eight patients were lost to follow-up (0.9%) and were censored. The statistical analysis is appropriate for the design of the study. All ESE examinations were reviewed by two independent observers and blinded to clinical data.

Elhendy 2004 (Exercise echocardiography)

Participants: A total of 437 (241 men and 196 women) patients were included in this study.

Inclusion criteria: The study included patients with a high pre test probability of CAD referred for exercise echocardiography. Exclusion criteria were a history MI; a previous coronary revascularisation procedure, CAD documented by angiography, and left ventricular hypertrophy. High pre-test probability of disease was defined as probability of >70%. This was considered in the presence of typical angina pectoris in women ≥ 50 years of age and in men ≥ 30 years of age.

Baseline characteristics: Mean age of the study patients was 65±10 years. Risk factors for CAD were hypertension in 208 patients (48%), diabetes mellitus in 32 (7%), hypercholesterolemia in 257 (59%) and smoking in 220 (50%).

Tests: Exercise echocardiography was done during symptom limited treadmill exercise testing (Bruce protocol 89%, Naughton protocol 6%, modified Bruce protocol 5%) with 12 channel electrocardiographic monitoring.

Exercise echocardiographic interpretation: Digitised and video tape-recorded images were used for interpretation. Regional wall motion was assessed semi quantitatively by an experienced echocardiographer who was blinded to clinical information. Wall motion at rest and during exercise was scored as 1 to 5 using a 16 segment model. Wall motion score index was determined at rest and during exercise as the sum of the segmental scores divided by the number of visualised segments. The difference between exercise and regional wall motion score index at rest was reported as mean wall motion score index. The development of new or increasing wall motion abnormality was considered indicative of myocardial ischaemia. A wall motion abnormality present at rest and unchanged with exercise was classified as fixed. Exercise echocardiographic results were defined as abnormal if there was ischaemia or fixed wall motion abnormalities. The exercise electrocardiogram was considered positive for ischaemia if there was horizontal or down sloping ST segment depression ≥1 mm at 80 ms after the J-point, non diagnostic if the baseline ST segment was abnormal, or negative for ischaemia in the absence of these criteria. Workload was measured in METs.

Follow-up: The follow-up was median 2.7 years (1 to 7.8 years).

Outcomes: The end points considered were 1) any cardiac events defined as coronary artery revascularization, non fatal MI and cardiac death 2) cardiac death and non fatal MI.

Statistical analysis: Univariable and multivariable associations of clinical and exercise echocardiographic variables with the end points were assessed in Cox’s proportional hazards models.

Results: During a median follow-up of 2.7 years, cardiac events occurred in 68 patients (16%). Four cardiac deaths and 15 non fatal MIs occured a median of 2.7 years after the exercise echocardiogram. 53 patients underwent revascularisation procedures (4 subsequently had non fatal MI). Revascularisation was early (<1 month) in 24 patients and late (>1 month) in 29 patients.

Table XUnivariate association of clinical, exercise stress test, and echocardiographic variables with risk of cardiac events

VariableChi-square (χ2)p-value; Risk ratio (95% CI)
Baseline characteristics
Smoker4.70.03; 1.72 (1.1 to 2.8)
Diabetes mellitus50.02; 2.3 (1.4 to 4.6)
Men190.0001; 0.25 (0.13 to 0.47)
Q waves on electrocardiogram4.30.04; 2.15 (1.05 to 4.42)
Exercise test variables
85% age predicted heart rate100.001; 0.45 (0.3 to 0.7)
Heart rate during exercise110.0009; 0.82 (0.74 to 0.90)
Systolic BP during exercise110.001; 0.9 (0.82 to 0.90)
Rate pressure product during exercise140.0002; 0.27 (0.14 to 0.53)
Workload (METs)50.03; 0.9 (0.8 to 0.99)
Exercise induced angina200.0001; 3 (1.9 to 4.9)
Ischaemic electrocardiographic changes270.0001; 3.8 (2.3 to 6.2)
Echocardiographic variables
Wall motion abnormality during exercise280.0001; 5.7 (3 to 10.8)
New wall motion abnormality (ischaemia)280.0001; 3.8 (2.3 to 6.3)
Percent ischaemic segments470.0001; 1.97 (1.62 to 2.39)
Wall motion score index during exercise450.0001; 4.4 (2.8 to 6.7)
Mean motion score index480.0001; 7 (4 to 12)

Table XIndependent predictors of cardiac events using a three step multivariate analysis model

ParametersChi-square (χ2)p-value*; model chi-square **
Clinical (model)
Age0.010.9; 36
Gender140.0002
Diabetes mellitus1.90.2
Clinical and exercise tests (model)
Ischaemic electrocardiographic changes3.20.07; 62 ***
Workload4.80.03
Clinical, exercise stress and echocardiography (model)
Wall motion abnormalities78 *****
In multi vessel regions****13.40.0003
In single vessel region****2.80.1
*

Chi square and p value based on final model.

**

Overall model chi-square at each phase of the modelling process

***

p=0.0001 versus the clinical model.

****

The reference group consisted of subjects with no wall motion abnormalities

*****

p=0.001 versus the clinical plus exercise stress model.

Summary: During a median follow-up of 2.7 years, cardiac death or non fatal MI occurred in 19 patients and 53 patients underwent coronary revascularisation. Event free survival rates in patients with normal versus abnormal stress echocardiograms were 98% versus 83% at 1 year, 96% versus 75% at 3 years, and 87% versus 69% at 5 years, respectively. In a multivariate analysis of clinical, exercise, and echocardiographic parameters, independent predictors of cardiac death and non-fatal MI were Q waves on the electrocardiogram (Chi-square 8.7, p=0.003) and the presence of wall motion of abnormalities during exercise in multi vessel distribution (Chi-square 5.3, p=0.02). In an incremental model of clinical, exercise and echocardiographic variables for the prediction of all cardiac events, the addition of echocardiographic data increased chi-square model from 62 to 78 (p=0.0003).

Strengths: The study sample represented the population of interest. The statistical analysis was appropriate for the design of the study.

Weakness: Loss to follow-up not reported. Very few events.

From: Appendix E, Included – Excluded Studies and Clinical Evidence Tables

Cover of Stable Angina
Stable Angina: Methods, Evidence & Guidance [Internet].
NICE Clinical Guidelines, No. 126.
National Clinical Guidelines Centre (UK).
Copyright © 2011, National Clinical Guidelines Centre.

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