Skip to main content

Advertisement

SpringerLink
Log in

The Foundational Role of Cardiovascular Imaging in the Characterization of Mental Stress–Induced Myocardial Ischemia in Patients with Coronary Artery Disease

  • Nuclear Cardiology (V Dilsizian, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Mental stress–provoked myocardial ischemia (MSIMI) is an ischemic phenomenon provoked by the experience of psychologically stressful circumstances. While MSIMI was initially identified 50 years ago during activities of daily living through the use of wearable Holter monitor, subsequent research utilized the technologies of cardiac imaging—ventriculography and myocardial perfusion—under controlled conditions to pursue an understanding of pathophysiology and prognosis. This work revealed that MSIMI occurs in almost half of patients with stable coronary artery disease (CAD) and is associated with cardiac events and early mortality. We provide a focused review of the instrumental role that cardiac imaging has played in elucidating how stress affects cardiac physiology and how emerging diagnostic techniques will allow for further research on stress-mediated changes in the coronary macro- and microvasculature.

Recent Findings

Observations about the cardiac response to mental stress diverge from underlying cornerstones of the traditional CAD paradigm which is based upon myocardial oxygen demand and the degree of epicardial coronary stenosis. Evidence from studies utilizing non-invasive and invasive studies of coronary perfusion indicates perturbations in the microvascular compartment in response to mental stress.

Summary

Cardiovascular imaging enjoined with mental stress provocation may be a commanding tool to advance our understanding of non-obstructive CAD and the coronary microvasculature. This further understanding will facilitate incorporation of mental stress testing in the clinical care of patients with discrepant diagnostic work-up of CAD and in patients who experience anginal symptoms due to non-exertional and/or emotional triggers. Such algorithms will be crucial to identify treatment targets to modify the risk associated with mental stress–associated ischemia and adverse prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ACS:

Acute coronary syndrome

BP:

Blood pressure

CAD:

Coronary artery disease

CFR:

Coronary flow reserve

ET-1:

Endothelin-1

HR:

Heart rate

INOCA:

Ischemia and no obstructive coronary artery disease

LVEF:

Left ventricular ejection fraction

MBF:

Myocardial blood flow

MI:

Myocardial infarction

MPI:

Myocardial perfusion imaging

MS:

Mental stress

MSIMI:

Mental stress–induced myocardial ischemia

PET:

Positron emission tomography

SPECT:

Single-photon emission computed tomography

SNS:

Sympathetic nervous system

SVR:

Systemic vascular resistance

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Burg MM, Vashist A, Soufer R. Mental stress ischemia: present status and future goals. J Nucl Cardiol. 2005;12:523–9.

    Article  PubMed  Google Scholar 

  2. Sheps DS, McMahon RP, Becker L, Carney RM, Freedland KE, Cohen JD, et al. Mental stress-induced ischemia and all-cause mortality in patients with coronary artery disease: results from the Psychophysiological Investigations of Myocardial Ischemia study. Circulation. 2002;105:1780–4.

    Article  PubMed  Google Scholar 

  3. Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. 2005;352:539–48.

    Article  CAS  PubMed  Google Scholar 

  4. Mittleman MA, Maclure M, Sherwood JB, Mulry RP, Tofler GH, Jacobs SC, et al. Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators. Circulation. 1995;92:1720–5.

    Article  CAS  PubMed  Google Scholar 

  5. Lampert R, Joska T, Burg MM, Batsford WP, McPherson CA, Jain D. Emotional and physical precipitants of ventricular arrhythmia. Circulation. 2002;106:1800–5.

    Article  PubMed  Google Scholar 

  6. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52.

    Article  PubMed  Google Scholar 

  7. Jain D, Burg M, Soufer R, Zaret BL. Prognostic implications of mental stress-induced silent left ventricular dysfunction in patients with stable angina pectoris. Am J Cardiol. 1995;76:31–5.

    Article  CAS  PubMed  Google Scholar 

  8. Kupper N, Denollet J, Widdershoven J, Kop WJ. Cardiovascular reactivity to mental stress and mortality in patients with heart failure. JACC Heart Fail. 2015;3:373–82.

    Article  PubMed  Google Scholar 

  9. Jiang W, Velazquez EJ, Kuchibhatla M, Samad Z, Boyle SH, Kuhn C, et al. Effect of escitalopram on mental stress-induced myocardial ischemia: results of the REMIT trial. JAMA. 2013;309:2139–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Soufer R, Bremner JD, Arrighi JA, Cohen I, Zaret BL, Burg MM, et al. Cerebral cortical hyperactivation in response to mental stress in patients with coronary artery disease. Proc Natl Acad Sci U S A. 1998;95:6454–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Krantz DS, Santiago HT, Kop WJ, Bairey Merz CN, Rozanski A, Gottdiener JS. Prognostic value of mental stress testing in coronary artery disease. Am J Cardiol. 1999;84:1292–7.

    Article  CAS  PubMed  Google Scholar 

  12. Blumenthal JA, Jiang W, Babyak MA, Krantz DS, Frid DJ, Coleman RE, et al. Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms. Arch Intern Med. 1997;157:2213–23.

    Article  CAS  PubMed  Google Scholar 

  13. Blumenthal JA, Babyak M, Wei J, O'Connor C, Waugh R, Eisenstein E, et al. Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in men. Am J Cardiol. 2002;89:164–8.

    Article  PubMed  Google Scholar 

  14. Pepine CJ, Schang SJ. Antianginal response of coronary heart disease patients on long-term perhexiline maleate. Am Heart J. 1975;35:168.

    Google Scholar 

  15. Schang SJ Jr, Pepine CJ. Transient asymptomatic S-T segment depression during daily activity. Am J Cardiol. 1977;39:396–402.

    Article  PubMed  Google Scholar 

  16. Imperi GA, Pepine CJ. Silent myocardial ischemia during daily activities: studies in asymptomatic patients and those with various forms of angina. Cardiol Clin. 1986;4:635–42.

    Article  CAS  PubMed  Google Scholar 

  17. Bellet S, Roman L, Kostis J, Slater A. Continuous electrocardiographic monitoring during automobile driving. Studies in normal subjects and patients with coronary disease. Am J Cardiol. 1968;22:856–62.

    Article  CAS  PubMed  Google Scholar 

  18. Stern S, Tzivoni D. Dynamic changes in the ST-T segment during sleep in ischemic heart disease. Am J Cardiol. 1973;32:17–20.

    Article  CAS  PubMed  Google Scholar 

  19. Gullette EC, Blumenthal JA, Babyak M, Jiang W, Waugh RA, Frid DJ, et al. Effects of mental stress on myocardial ischemia during daily life. Jama. 1997;277:1521–6.

    Article  CAS  PubMed  Google Scholar 

  20. Schiffer F, Hartley LH, Schulman CL, Abelmann WH. The quiz electrocardiogram: a new diagnostic and research technique for evaluating the relation between emotional stress and ischemic heart disease. Am J Cardiol. 1976;37:41–7.

    Article  CAS  PubMed  Google Scholar 

  21. Soufer R, Burg MM. The heart-brain interaction during emotionally provoked myocardial ischemia: implications of cortical hyperactivation in CAD and gender interactions. Cleve Clin J Med. 2007;74(Suppl 1):S59–62.

    Article  PubMed  Google Scholar 

  22. Tracey KJ. The inflammatory reflex. Nature. 2002;420:853–9.

    Article  CAS  PubMed  Google Scholar 

  23. Deanfield JE, Shea M, Kensett M, Horlock P, Wilson RA, de Landsheere CM, et al. Silent myocardial ischaemia due to mental stress. Lancet. 1984;2:1001–5.

    Article  CAS  PubMed  Google Scholar 

  24. Jiang W, Samad Z, Boyle S, Becker RC, Williams R, Kuhn C, et al. Prevalence and clinical characteristics of mental stress-induced myocardial ischemia in patients with coronary heart disease. J Am Coll Cardiol. 2013;61:714–22.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kaufmann PG, McMahon RP, Becker LC, Bertolet B, Bonsall R, Chaitman B, et al. The Psychophysiological Investigations of Myocardial Ischemia (PIMI) study: objective, methods, and variability of measures. Psychosom Med. 1998;60:56–63.

    Article  CAS  PubMed  Google Scholar 

  26. Becker LC, Pepine CJ, Bonsall R, Cohen JD, Goldberg AD, Coghlan C, et al. Left ventricular, peripheral vascular, and neurohumoral responses to mental stress in normal middle-aged men and women. Reference Group for the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study. Circulation. 1996;94:2768–77.

    Article  CAS  PubMed  Google Scholar 

  27. Kim D, Ha JW. Hypertensive response to exercise: mechanisms and clinical implication. Clin Hypertens. 2016;22:17.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Arrighi JA, Burg M, Cohen IS, Soufer R. Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease. J Nucl Cardiol. 2003;10:267–74.

    Article  PubMed  Google Scholar 

  29. Yeung AC, Vekshtein VI, Krantz DS, Vita JA, Ryan TJ Jr, Ganz P, et al. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med. 1991;325:1551–6.

    Article  CAS  PubMed  Google Scholar 

  30. Kop WJ, Krantz DS, Howell RH, Ferguson MA, Papademetriou V, Lu D, 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;37:1359–66.

    Article  CAS  PubMed  Google Scholar 

  31. Arrighi JA, Burg M, Cohen IS, Kao AH, Pfau S, Caulin-Glaser T, et al. Myocardial blood-flow response during mental stress in patients with coronary artery disease. Lancet. 2000;356:310–1.

    Article  CAS  PubMed  Google Scholar 

  32. Ramadan R, Quyyumi AA, Zafari AM, Binongo JN, Sheps DS. Myocardial ischemia and angiotensin-converting enzyme inhibition: comparison of ischemia during mental and physical stress. Psychosom Med. 2013;75:815–21.

    Article  CAS  PubMed  Google Scholar 

  33. Burg MMPT. The cardiovascular system. In: Baum A, Contrada RJ, editors. The handbook of stress science: biology, psychology, and health. New York: Springer; 2010.

    Google Scholar 

  34. Lampert R, Jain D, Burg MM, Batsford WP, McPherson CA. Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Circulation. 2000;101:158–64.

    Article  CAS  PubMed  Google Scholar 

  35. Dietz NM, Rivera JM, Eggener SE, Fix RT, Warner DO, Joyner MJ. Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans. J Physiol. 1994;480:361–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. •• D’Urzo KA, La Rocque CL, Williams JS, Stuckless TJR, King TJ, Plotnick MD, et al. The impact of acute mental stress on brachial artery flow-mediated dilation in women diagnosed with depression. Int J Psychophysiol. 2019;135:113–20.

    Article  PubMed  Google Scholar 

  37. Harris CW, Edwards JL, Baruch A, Riley WA, Pusser BE, Rejeski WJ, et al. Effects of mental stress on brachial artery flow-mediated vasodilation in healthy normal individuals. Am Heart J. 2000;139:405–11.

    CAS  PubMed  Google Scholar 

  38. Gottdiener JS, Kop WJ, Hausner E, McCeney MK, Herrington D, Krantz DS. Effects of mental stress on flow-mediated brachial arterial dilation and influence of behavioral factors and hypercholesterolemia in subjects without cardiovascular disease. Am J Cardiol. 2003;92:687–91.

    Article  PubMed  Google Scholar 

  39. Shimbo D, Rosenberg LB, Chaplin W, Zhao S, Goldensohn ER, Cholankeril M, et al. Endothelial cell activation, reduced endothelial cell reparative capacity, and impaired endothelial-dependent vasodilation after anger provocation. Int J Cardiol. 2013;167:1064–5.

    Article  PubMed  Google Scholar 

  40. •• Hammadah M, Kim JH, Al Mheid I, Samman Tahhan A, Wilmot K, Ramadan R, et al. Coronary and peripheral vasomotor responses to mental stress. J Am Heart Assoc. 2018;7:e008532. In the physiologic study of coronary and peripheral vascular response to mental stress, mental stress–induced increases on coronary microvascular resistence that correlated with endothelial-dependepent pathways and coronary microvascular alterations were associated with peripheral vasomotion, thus highlighting the role of the endothelium and coronary microvascular and highlighting an important link to peripheral vasculature.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. •• Lima BB, Hammadah M, Kim JH, Uphoff I, Shah A, Levantsevych O, et al. Association of transient endothelial dysfunction induced by mental stress with major adverse cardiovascular events in men and women with coronary artery disease. JAMA Cardiol. 2019;4:988–96. Laboratory mental stress–induced endothelial dysfunction, as measured by brachial artery flow-mediated dilation, predicted adverse cardiovascular outcomes at 3–5 years (hazard ratio 1.78 [95% CI, 1.15–2.76]).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yang ZH, Richard V, von Segesser L, Bauer E, Stulz P, Turina M, et al. Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation. 1990;82:188–95.

    Article  CAS  PubMed  Google Scholar 

  43. Burg MM, Soufer A, Lampert R, Collins D, Soufer R. Autonomic contribution to endothelin-1 increase during laboratory anger-recall stress in patients with coronary artery disease. Mol Med. 2011;17:495–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Spieker LE, Hurlimann D, Ruschitzka F, Corti R, Enseleit F, Shaw S, et al. Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors. Circulation. 2002;105:2817–20.

    Article  CAS  PubMed  Google Scholar 

  45. Arbab-Zadeh A, Nakano M, Virmani R, Fuster V. Acute coronary events. Circulation. 2012;125:1147–56.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sharaf BL, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, et al. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory). Am J Cardiol. 2001;87:937–41 A3.

    Article  CAS  PubMed  Google Scholar 

  47. Blumenthal JA, Sherwood A, Smith PJ, Watkins L, Mabe S, Kraus WE, et al. Enhancing cardiac rehabilitation with stress management training: a randomized, clinical efficacy trial. Circulation. 2016;133:1341–50.

    Article  PubMed  PubMed Central  Google Scholar 

  48. •• Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, et al. Stratified medical therapy using invasive coronary function testing in angina: the CorMicA trial. J Am Coll Cardiol. 2018;72:2841–55.

    Article  PubMed  Google Scholar 

  49. Shah SM, Pfau SE. Coronary physiology in the cardiac catheterization laboratory. J Clin Med. 2019;8.

  50. Rahman H, Ryan M, Lumley M, Modi B, McConkey H, Ellis H, et al. Coronary microvascular dysfunction is associated with myocardial ischemia and abnormal coronary perfusion during exercise. Circulation. 2019;140:1805–16.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Kaplan RM, Milstein A. Contributions of health care to longevity: a review of 4 estimation methods. Ann Fam Med. 2019;17:267–72.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140:e596–646.

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by grants from the National Heart, Lung and Blood Institute to Dr. Soufer (R01HL 59619) and Dr. Burg (R01HL126770), and Dr. Soufer’s Merit Review Award from the Dept. Veteran Affairs.

Author information

Authors and Affiliations

  1. Section of Cardiovascular Medicine, Yale School of Medicine, 950 Campbell Ave. / 111B, West Haven, CT, 06516, USA

    Judith L. Meadows, Samit Shah, Matthew M. Burg, Steven Pfau & Robert Soufer

  2. VA Connecticut Healthcare System, West Haven, CT, USA

    Judith L. Meadows, Samit Shah, Matthew M. Burg, Steven Pfau & Robert Soufer

Authors
  1. Judith L. Meadows
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samit Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew M. Burg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven Pfau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Soufer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert Soufer.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Nuclear Cardiology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meadows, J.L., Shah, S., Burg, M.M. et al. The Foundational Role of Cardiovascular Imaging in the Characterization of Mental Stress–Induced Myocardial Ischemia in Patients with Coronary Artery Disease. Curr Cardiol Rep 22, 162 (2020). https://doi.org/10.1007/s11886-020-01407-w

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11886-020-01407-w

Keywords

Search

Navigation