Variability of myocardial ischemic responses to mental versus exercise or adenosine stress in patients with coronary artery disease

doi:10.1016/j.nuclcard.2008.04.005

Journal of Nuclear Cardiology

Volume 15, Issue 4, July–August 2008, Pages 518-525

https://doi.org/10.1016/j.nuclcard.2008.04.005 Get rights and content

Background

Mental stress precipitates myocardial ischemia in a significant percentage of coronary artery disease (CAD) patients. Exercise or adenosine stresses produce different physiologic responses and cause myocardial ischemia via different mechanisms. Little is known about the comparative severity and location of myocardial ischemia provoked by these different stressors. In this study we sought to compare the within-individual ischemic responses to mental versus exercise or adenosine stress in a cohort of CAD patients.

Methods and Results

All patients underwent mental stress and either exercise or adenosine testing within a 1-week period. Mental stress was induced via a public speaking task. Rest-stress myocardial perfusion imaging was used with all testing protocols. Participants were 187 patients (65 women [35%]) with a documented history of CAD and a mean age of 64 ± 9 years. Mental stress–induced myocardial ischemia (MSIMI) was less prevalent and frequently of less magnitude than exercise- or adenosine-induced ischemia. Ischemia induced by exercise or adenosine testing did not accurately predict the development or the location of MSIMI. The overall concordance between these stressors for provoking ischemia was weak (percent agreement, 71%; κ [± SE], 0.26 ± 0.07). In a minority of patients (11%) mental stress provoked ischemia in the absence of exercise- or adenosine-induced ischemia. Moreover, in patients who had myocardial ischemia during both stressors, there were significant within-individual differences in the coronary artery distribution of the ischemic regions. MSIMI was more likely to occur in a single-vessel distribution (86%) compared with exercise- or adenosine-induced ischemia (54%). The stressors had moderate agreement if the ischemic region was in the right coronary artery territory (percent agreement, 76%; κ, 0.52 ± 0.19) or the left anterior descending coronary artery (percent agreement, 76%; κ, 0.51 ± 0.19) and significantly lower agreement in the left circumflex territory (percent agreement, 62%; κ, 0.22 ± 0.18).

Conclusions

Our findings indicate that mental and exercise or adenosine stresses provoke different myocardial ischemic responses. These observations suggest that exercise or adenosine testing may not adequately assess the likelihood of occurrence or severity of MSIMI and that different mechanisms are operative in each condition.

Section snippets

Study Design

The study protocol was approved by the University of Florida Institutional Review Board (Gainesville, Fla). Informed consent was obtained from all participants. In random order, all patients underwent mental stress and exercise or adenosine stress testing on separate mornings within a 1-week period. None of the participants had any changes in their medications or clinical status between the testing sessions. The tests were conducted after an overnight fast. β-Blockers, calcium channel blockers,

Patient Characteristics and Baseline Data

A total of 187 patients were studied; 65 of these (35%) were women. The mean age was 64 ± 9 years. The majority of patients (88%) were white, whereas 7% were black. All participants had CAD. Of the patients, 65% satisfied entry criteria based on abnormal coronary angiograms, 35% had a history of coronary artery bypass graft surgery, 19% had prior MI, and 63% had a history of anginal symptoms. Other comorbid medical conditions included diabetes (32%), hypertension (78%), hyperlipidemia (89%),

Discussion

Our findings in this study indicate that there is a significant variability in ischemic responses to mental versus exercise or adenosine stress. The overall concordance for provoking ischemia between these testing modalities was weak (percent agreement, 71%; κ, 0.26). In a minority of patients (11%) mental stress provoked ischemia in the absence of exercise- or adenosine-induced ischemia. Moreover, among the patients who had myocardial ischemia during both stressors, there were significant

Limitations

Arguably, many factors may be involved in the observed variability reported in this study. Variabilities in image acquisition techniques, image interpretation, image quality, and attenuation artifacts may all account for some of the observed differences. Differences in the potency of stressors used is another factor. There are established criteria for ensuring adequacy of exercise stress testing—that is, patients having achieved at least 85% of their age-predicted HR.¹³ No such criterion has

Conclusion

Our findings in this study indicate that there is marked variability in ischemic responses to exercise or adenosine versus mental stress testing. Whatever the underlying mechanisms, it will be important to determine whether mental stress testing provides additional risk prediction above and beyond the other traditional risk stratification tools in different categories of patients.

Acknowledgment

The authors have indicated they have no financial conflicts of interest.

References (32)

J.S. Gottdiener et al.
Induction of silent myocardial ischemia with mental stress testing: Relation to the triggers of ischemia during daily life activities and to ischemic functional severity
J Am Coll Cardiol
(1994)
F.H. Gabbay et al.
Triggers of myocardial ischemia during daily life in patients with coronary artery disease: Physical and mental activities, anger and smoking
J Am Coll Cardiol
(1996)
D. Jain et al.
Prognostic implications of mental stress-induced silent left ventricular dysfunction in patients with stable angina pectoris
Am J Cardiol
(1995)
D.S. Krantz et al.
Prognostic value of mental stress testing in coronary artery disease
Am J Cardiol
(1999)
S. Ramachandruni et al.
Mental stress provokes ischemia in coronary artery disease subjects without exercise- or adenosine-induced ischemia
J Am Coll Cardiol
(2006)
D.S. Sheps et al.
Heterogeneity among cardiac ischemic and anginal responses to exercise, mental stress, and daily life
Am J Cardiol
(1998)
D.J. Pennell et al.
Adenosine combined with dynamic exercise for myocardial perfusion imaging
J Am Coll Cardiol
(1995)
P.J. LaVeau et al.
Transient left ventricular dysfunction during provocative mental stress in patients with coronary artery disease
Am Heart J
(1989)
M.D. Cerqueira et al.
American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac ImagingStandardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association
J Nucl Cardiol
(2002)
N.C. Gupta et al.
The GE SPECT Multicenter Adenosine Study Group, Comparison of adenosine and exercise thallium-201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging
J Am Coll Cardiol
(1992)

S. Nishimura et al.

Equivalence between adenosine and exercise thallium-201 myocardial tomography: A multicenter, prospective, crossover trial

J Am Coll Cardiol

(1992)

A. Cuocolo et al.

Technetium 99m-labeled tetrofosmin myocardial tomography in patients with coronary artery disease: Comparison between adenosine and dynamic exercise stress testing

J Nucl Cardiol

(1996)

V. Papademetriou et al.

Transient coronary occlusion with mental stress

Am Heart J

(1996)

W.J. Kop et al.

Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: Relationship with hemodynamic stress responses

J Am Coll Cardiol

(2001)

J.A. Arrighi et al.

Myocardial blood-flow response during mental stress in patients with coronary artery disease

Lancet

(2000)

A. Elhendy et al.

Accuracy of exercise stress technetium 99m sestamibi SPECT imaging in the evaluation of the extent and location of coronary artery disease in patients with an earlier myocardial infarction

J Nucl Cardiol

(2000)

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Microcirculatory dysfunction during psychological stress may lead to diffuse myocardial ischemia. We developed a novel quantification method for diffuse ischemia during mental stress (dMSI) and examined its relationship with outcomes after a myocardial infarction (MI). We studied 300 patients ≤ 61 years of age (50% women) with a recent MI. Patients underwent myocardial perfusion imaging with mental stress and were followed for 5 years. dMSI was quantified from cumulative count distributions of rest and stress perfusion. Focal ischemia was defined in a conventional fashion. The main outcome was a composite outcome of recurrent MI, heart failure hospitalizations, and cardiovascular death. A dMSI increment of 1 standard deviation was associated with a 40% higher risk for adverse events (HR 1.4, 95% CI 1.2–1.5). Results were similar after adjustment for viability, demographic and clinical factors and focal ischemia. In sex-specific analysis, higher levels of dMSI (per standard deviation increment) were associated with 53% higher risk of adverse events in women (HR 1.5, 95% CI 1.2–2.0) but not in men (HR 0.9, 95% CI 0.5–1.4), P 0.001. A novel index of diffuse ischemia with mental stress was associated with recurrent events in women but not in men after MI.
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Citation Excerpt :
It is possible that the physiological stress induced by the challenge on the myocardium was not sufficient to induce ischemia in patients with normal exercise stress tests. In fact, a few recent reports have shown that only between 11 and 29% of CAD patients with normal nuclear exercise stress tests have mental stress-induced ischemia [15,33,34]. In addition, animal work suggests that normal coronary arteries tend to dilate during mental stress, whereas diseased portions of arteries constrict [35].
We have previously reported that 35% CO₂ challenge induced myocardial ischemia in 81% of coronary artery disease (CAD) patients with comorbid panic disorder (PD) and previous positive nuclear exercise stress tests. However, it is yet unclear whether this is the case among CAD patients with PD and normal nuclear exercise stress test results. We hypothesized that a potent mental stressor such as a panic challenge among CAD patients with PD would also induce ischemia in patients with normal exercise stress tests.
Forty-one coronary artery disease patients with normal nuclear exercise stress tests (21 patients with PD and 20 without PD) were submitted to a well-established panic challenge test (with 1 vital capacity inhalation of a gas mixture containing 35% CO₂ and 65% O₂) and injected with Tc-99m-tetrofosmin (Myoview), upon inhalation. Single photon emission computed tomography imaging was used to assess per-panic challenge reversible myocardial ischemia and HR, BP, and a 12 lead ECG was continuously measured during the procedure.
Fifty-eight percent of panic disorder patients (12/21) had a panic attack during the panic challenge vs 15% (3/20) of controls (p = 0.005). Only 10% of patients in each group displayed myocardial ischemia per panic challenge.
These findings suggest that panic attacks among panic disorder patients with lower-risk coronary artery disease may not confer a risk for myocardial ischemia.
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: This study was supported by grants HL 070265 and HL 072059 from the National Heart, Lung, and Blood Institute. This material is also the result of work supported by resources and the use of facilities at the Department of Veterans Affairs Medical Center, Gainesville, Fla.

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Original articleVariability of myocardial ischemic responses to mental versus exercise or adenosine stress in patients with coronary artery disease

Background

Methods and Results

Conclusions

Section snippets

Study Design

Patient Characteristics and Baseline Data

Discussion

Limitations

Conclusion

Acknowledgment

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Am Heart J

J Nucl Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Nucl Cardiol

Am Heart J

J Am Coll Cardiol

Lancet

J Nucl Cardiol

Original article
Variability of myocardial ischemic responses to mental versus exercise or adenosine stress in patients with coronary artery disease