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. 2019 Dec 10;140(24):1971-1980.
doi: 10.1161/CIRCULATIONAHA.119.042918. Epub 2019 Nov 11.

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA

Rasha K Al-Lamee  1   2 , Matthew J Shun-Shin  1   2 , James P Howard  1   2 , Alexandra N Nowbar  1   2 , Christopher Rajkumar  1   2 , David Thompson  1 , Sayan Sen  1   2 , Sukhjinder Nijjer  1   2 , Ricardo Petraco  1   2 , John Davies  3   4 , Thomas Keeble  3   4 , Kare Tang  3 , Iqbal Malik  1   2 , Nina Bual, Christopher Cook  1   2 , Yousif Ahmad  1   2 , Henry Seligman  1   2 , Andrew S P Sharp  5 , Robert Gerber  6 , Suneel Talwar  7 , Ravi Assomull  2 , Graham Cole  1   2 , Niall G Keenan  8 , Gajen Kanaganayagam  2 , Joban Sehmi  8 , Roland Wensel  1 , Frank E Harrell Jr  9 , Jamil Mayet  1   2 , Simon Thom  1 , Justin E Davies  2 , Darrel P Francis  1   2
Affiliations

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA

Rasha K Al-Lamee et al. Circulation. .

Abstract

Background: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina).

Methods: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling.

Results: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426).

Conclusions: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Keywords: angina, stable; coronary artery disease; echocardiography, stress; percutaneous coronary intervention.

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Figures

Figure 1.
Figure 1.
Relationship between prerandomization stress echocardiography score and prerandomization FFR and iFR. A, Relationship between prerandomization stress echocardiography score and prerandomization FFR. B, Relationship between prerandomization stress echocardiography score and prerandomization iFR. echo indicates echocardiography; FFR, fractional flow reserve; and iFR, instantaneous wave-free ratio.
Figure 2.
Figure 2.
Relationship of treatment difference in Seattle Angina Questionnaire (SAQ) angina frequency score at follow-up to prerandomization stress echocardiography score by randomization arm. There is a significant interaction between stress echocardiography score and Seattle Angina Frequency score with a progressive tendency for larger effects on angina frequency score with higher stress echocardiography score (Pinteraction=0.031). echo indicates echocardiography; and PCI, percutaneous coronary intervention.
Figure 3.
Figure 3.
Relationship of treatment difference in freedom from angina and prerandomization stress echocardiography by randomization arm. There is no discernible dependence on prerandomization stress echocardiography score. echo indicates echocardiography; and PCI, percutaneous coronary intervention.
Figure 4.
Figure 4.
Relationship of treatment difference in Seattle Angina Questionnaire (SAQ) physical limitation score and prerandomization stress echocardiography by randomization arm. There is no discernible dependence on prerandomization stress echocardiography score. echo indicates echocardiography; and PCI, percutaneous coronary intervention.
Figure 5.
Figure 5.
Relationship of treatment difference in exercise time and prerandomization stress echocardiography by randomization arm. There is no discernible dependence on prerandomization stress echocardiography score. echo indicates echocardiography; and PCI, percutaneous coronary intervention.
Figure 6.
Figure 6.
A proposed sequence of steps in the pathway of ischemia. Coronary stenosis (step A) causes coronary hemodynamic insufficiency (step B) which leads to stress-induced myocardial ischemia. This manifests as wall motion abnormalities on imaging tests (step C) and causes pain that is verbalized by the patient (step D) and recorded by the physician (step E). The magnitude of association between measurements is likely to be stronger between adjacent steps than steps further apart.
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References

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