Mental stress-induced myocardial ischaemia in a middle-aged woman with nonobstructive coronary artery disease: case report

Abstract

Introduction

Psychosocial stress can drive biological response, and is perceived as strongly associated with cardiovascular disorders in recent years, especially for young and middle-aged women.¹ Mental stress-induced myocardial ischaemia (MSIMI), independent from conventional atherosclerotic ischaemia and standard risk factors, is a transient ischaemic response in the heart under mental stress. Studies have shown that MSIMI is two-fold more common among women than in men, and can indicate a two-fold increased risk of adverse outcomes including cardiovascular events.^2,3 Diagnosis for MSIMI remains enigma for physicians given that ischaemia provoked by mental stress is not primarily evaluated in the current clinical setting, and laboratory tests including psychological scales and structural mental stress testing are performed only when psychosocial factors are considered, or if traditional management is not therapeutic. We demonstrate a case of an angina patient with nonobstructive coronary artery disease (CAD) and incident diagnosis of MSIMI that was confirmed by both contrast-enhanced echocardiography and positron emission tomography (PET). The treatment strategy was accordingly altered with anti-anxiety management.

Summary figure

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Case presentation

A 40-year-old female bus driver was presented for recurrent chest pain over the past six months. She often woke up with pain early in the morning, and the discomfort was characterized by subxiphoid stuffy pain radiating to the left chest, shoulder, and arm, which lasted <2 min with spontaneous remission. The episodes became more frequent in the recent month. The patient reported no past medical history, family history of premature CAD, and traditional cardiovascular risk factor except for a body mass index of 24.7 and previous light smoking. Blood pressure was 117/76 mmHg. The laboratory tests were unremarkable including normal serum N-terminal pro-B-type natriuretic peptide and troponin level. Low density lipoprotein cholesterol level was 1.34 mmol/L, and glycosylated haemoglobin (HbA1c) level was 5.3%. Her treadmill exercise test taken in another hospital 3 months before was positive, with ST-segment depression in II, III, and avF leads (>1 mv), as well as anterior wall leads (0.8 mv) during the test (Figure 1). The patient was diagnosed with CAD. The following invasive coronary angiography in that hospital showed 40% stenosis in the middle segment of the left anterior descending artery (Figure 2), and coronary spasm was also considered given that the guide wire was blocked when passing through the brachial artery. The patient was discharged and treated with diltiazem, aspirin, and rosuvastatin for 3 months. She reported certain relief of discomfort with decrease in both frequency and intensity, but still suffered from episodic pain below the xiphoid. The patient had serial miserable life experience before suffering from the refractory angina. She became emotionally charged and often cried after witnessing her father-in-law crushed to death by a falling building 8 years before, followed by discovering the infidelity of her husband the next year. The patient was referred to our hospital for further assessment of the role of mental stress in the aetiology of angina. She reported depression and poor sleep quality. Psychological scale evaluation, including Perceived Stress Scale and Hospital Anxiety and Depression Scale, suggested that the patient was in a state of high stress, anxiety, and depression. Left ventricular ejection fraction (LVEF) was normal (62%) on routine transthoracic echocardiography, and apparent structural heart disease was excluded. Myocardial perfusion imaging including contrast-enhanced echocardiography and PET with N-13 ammonia during mental stress testing were scheduled on separate days.

Figure 1

ECG showing ST-segment depression in the inferior and anterior wall leads during treadmill exercise test.

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Figure 2

Coronary angiography in another hospital demonstrating 40% stenosis in the middle segment of the left anterior descending artery (black arrow).

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Mental stress testing was conducted in the morning with a fasting state. Diltiazem was discontinued one day before test. The patient was settled in a quiet and dim room, with a tailored head-mounted virtual reality device. Three pre-set mental stress tasks, including modified Stroop test, public speech, and mental arithmetic, were executed in sequence after a 15-min rest, with each task lasting 3–4 min. Echocardiography with contrast agent was performed at rest, the third minute and seventh minute of the testing and recovery, respectively. The patient was emotionally devoted and cried with grief when recalling her painful experiences during the part of public speech. She reported mild chest pain shortly after the speech task ended, which gradually aggravated with concomitant sweat. Apical perfusion delay (∼4 s) in replenishment following high-mechanical index (MI) flash impulse series was simultaneously observed on myocardial contrast echocardiography, along with hypokinetic regional wall motion and thickening abnormality at the left ventricular apex (Figure 3A and B, Supplementary material online, Videos S1 and S2). A reduced LVEF (42%) compared to admission was noted, and left ventricular global longitudinal strain (GLS) was −17.1% (normal value < −20%) (Figure 3C). The patient was asked to take deep breathing in supine position to calm down. The chest pain was relieved without further intervention, and apical wall motion went back to normal on real-time echocardiography with normal LVEF and GLS measurements. Summed difference score (SDS), defined as difference between PET scans during mental stress testing and at rest carried out 1 or 2 days before enhanced echocardiography, was 3 (Figure 4), which also revealed myocardial ischaemia.⁴ Hence, the patient was newly diagnosed with MSIMI.

Figure 3

Echocardiography. Subendocardial perfusion delay in replenishment (A) and wall thickening abnormality (B) in the left ventricular apex at apical four-chamber view on myocardial contrast echocardiography during mental stress testing. The right panel (C) shows reduced values of left ventricular ejection fraction and global longitudinal strain.

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Figure 4

Mental stress-induced myocardial ischaemia diagnosed on PET myocardial perfusion imaging [(A) rest and (B) mental stress].

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Reactive hyperaemia index (RHI, normal value ≥ 1.68) reflecting peripheral microvascular function⁵ was measured on Endo-PAT 2000 (Itamar Medical Ltd, Caesarea, Israel), and showed mild decline 30 min after mental stress testing when compared to rest (1.6 vs. 2.0). Endothelial dysfunction was therefore noted. Coronary flow reserve (CFR) calculated with adenosine test on PET performed the day before enhanced echocardiography was 3.5, demonstrating normal endothelium-independent microvascular function. The patient was finally diagnosed with microvascular angina and MSIMI. Escitalopram was added to the treatment of her previous triple therapy to ease her anxiety. She also kept regular low-intensity exercise as recommended. The patient reported much less chest pain and anxiety during one month follow-up after discharge.

Discussion

We reported an incidental case of an angina woman in her midlife with no obstructive CAD proved to be MSIMI by definite diagnosis on both echocardiography and PET. The precise diagnostic workflow, especially mental stress testing, played a vital role in the appropriate therapeutic strategy. Comprehensive management with escitalopram and exercise superimposed on traditional drug treatment finally contributed to a reasonable recovery following patient discharge.

Conventional criteria for MSIMI diagnosis include a new or worse wall motion abnormality (WMA), reduction of LVEF ≥ 8%, ST-segment depression or elevation in ≥2 leads over 3 or more consecutive cycles,⁶ and/or a SDS (difference between summed stress score and summed rest score) ≥ 3 calculated on nuclear perfusion imaging.⁴ Mental stress-induced myocardial ischaemia was confirmed in the present case on PET that is generally accepted to be the non-invasive standard to assess myocardial ischaemia. Echocardiography revealed regional WMA and reduction of LVEF during mental stress testing in the case, which also fitted into the diagnostic criteria of MSIMI. Global longitudinal strain, as a more sensitive index of systolic dysfunction than LVEF, also showed a considerable decrease in the subsequent analysis. One remarkable issue of the case is the diagnostic value of contrast-enhanced echocardiography that had a crucial role in MSIMI diagnosis in the present case. Regional subendocardial ischaemia was indicated by the perfusion defect early after the destructive flash pulse sequence in the apex, which, during demand stress test, has been confirmed to occur before WMA in light of the ischaemic cascade.⁷ The use of perfusion analysis in conjunction with reversible left ventricular systolic function index (LVEF and GLS) in our case showed diagnostic consistency and accuracy in the assessment of MSIMI that was defined on PET imaging. As far as we know, similar circumstance has not yet been published before. Perfusion echocardiography has shown higher spatial resolution than radioactive PET, and hence can permit more sensitivity in myocardial ischaemia detection.⁸

The patient had both exercise-induced myocardial ischaemia and MSIMI that don’t necessarily co-occur. Mental stress-induced myocardial ischaemia is more common and usually occurs at a lower cardiovascular workload compared to exercise stress-induced ischaemia.⁹ The pathogenesis may lie in abnormal vasomotion of the coronary arterioles, or rather, their inability to adequately dilate,¹⁰ although the underlying mechanism remains undiscovered. It is believed that atherosclerotic burden is involved in exercise-induced myocardial ischaemia, while microvascular abnormalities are associated with MSIMI which indicates a worse prognosis irrespective of traditional physical stress testing.^11,12 Mental stress-induced myocardial ischaemia could better predict adverse cardiovascular outcomes than exercise stress ischaemia with combination of the two showing the best predictive ability.³ Endothelial dysfunction was indicated in the patient by mild impaired RHI shortly after mental stress testing, which may provide important pathological basis for MSIMI and also account for positive exercise test encountered in the setting of normal CFR. Another potential mechanism of MSIMI could be epicardial coronary spasm (paradoxical vasoconstriction) provoked by adrenergic stimulation during acute mental stress.¹⁰ Intracoronary acetylcholine test was lacked in our case to define endothelial dysfunction and rule out spasm in the large epicardial arteries. However, the pathological basis for MSIMI is considered to reside in the microvasculature given that myocardial blood volume stays constant during MSIMI.¹³

A multidisciplinary care approach including psychosocial stress management has been recommended by the expert consensus document on ischaemia with nonobstructive coronary arteries (INOCA) in collaboration with the European Society of Cardiology.¹⁴ As a special form of INOCA, there are still many issues unresolved concerning MSIMI management. Pharmacotherapy specific for psychosocial factors involvement even mental disorders has been proven effective. Escitalopram was shown to help in the present case. Jiang et al.¹⁵ demonstrated that 6 weeks of escitalopram treatment vs. placebo could improve MSIMI by reducing negative emotions and haemodynamic responses to mental stress through enhancement of serotonergic function. The patient also benefited from regular exercise.

Conclusion

Mental stress-induced myocardial ischaemia is more likely developed in women, especially young women, compared with men of similar age. However, there has been rare report on MSIMI in women with nonobstructive CAD despite their common microvascular pathological basis. Psychosocial stress should be further investigated in women with angina but nonobstructive coronary arteries. Comprehensive management including specific drug therapy coping with stress could significantly improve the prognosis and quality of life in patients with MSIMI.

Lead author biography

Dr Bo Kong is currently working as a sonographer at the Cardiovascular Institute of Guangdong Provincial People’s Hospital (Guangzhou, China). She focused on clinical research in myocardial contrast echocardiography and received her MD degree at South China University of Technology.

Supplementary material

Supplementary material is available at European Heart Journal – Case Reports online.

Consent: The patient gave consent to appear in the publication in compliance with the COPE guidelines.

Funding: This work was supported by the Basic and Applied Basic Research of Guangzhou Science and Technology Bureau for young doctor sailing project [2025A04J4772] and National Natural Science Foundation of China [82371963].

Ethics approval

All authors comply with the World Medical Association Declaration of Helsinki, and the research protocol was approved by the Ethics Committee of Guangdong Provincial People’s Hospital (No.GDREC2019298H).

Data availability

The data underlying this article are available in the article and in its online Supplementary material.

References

Author notes