Panic disorder and coronary artery spasm

Whatever the causative mechanism, prolonged chest pain during panic attacks requires investigation

MJA 1998; 168: 376-377  

The three cases reported by Mansour et al1 in this issue of the Journal add to the evidence for increased risk of adverse cardiovascular events in people with severe anxiety. The existing evidence derives from both prospective epidemiological studies2,3 and controlled longitudinal clinical studies.4 In the latter, mortality was related to severity of emotional arousal; panic disorder patients were at greater risk of sudden cardiac death than patients with lesser forms of anxiety, such as generalised anxiety disorder. Two of the cases reported by Mansour et al (Patients 1 and 3) showed a close temporal association between panic attacks and ischaemic chest pain. In the absence of severe obstructive coronary disease, might the ischaemia be due to coronary artery spasm? Patient 1 presented with severe chest pain accompanying episodes of panic. An electrocardiogram (ECG) showed mild tachycardia and ST-segment depression, but no cardiac enzymes were released, and the coronary angiogram was normal. With subsequent panic attacks, the patient continued to experience anginal pain, which resolved completely after prescription of amlodipine (a potent dihydropyridine calcium antagonist known to prevent epicardial coronary spasm). Patient 3 had long-standing panic disorder and mild hypertension. He had acute ischaemic chest pain during a panic attack; cardiac enzyme levels were raised, and infarction was diagnosed. Angiography showed no underlying atherosclerosis. Angina-like chest pain occurred during subsequent panic attacks, but once again resolved completely after amlodipine therapy. The other patient (Patient 2) experienced an infarct associated with exercise rather than with an acute panic attack. Coronary angiography during the acute stage showed that the infarct-related artery was occluded, while the other coronary arteries were normal. The patient had a nine-year history of panic disorder, and previous panic attacks had been accompanied by chest pain. However, no chest pain occurred during post-infarction panic attacks, and there was no temporal relationship between panic attacks and the major ischaemic episode. Although coronary artery spasm is one of the plausible mechanisms for the cardiac ischaemia, none of these patients had convincing evidence of spasm during panic attacks. Spasm of an epicardial coronary artery usually results in ST-segment elevation, which accompanies transmural ischaemia. A definitive diagnosis of coronary spasm requires demonstration of ST-segment elevation, or spasm at angiography, during spontaneous angina or after provocation with ergonovine, acetylcholine or hyperventilation. In Patient 1, the ECG during chest pain showed ST-segment depression, while in Patient 3 no ECG changes were seen. While coronary spasm with ST-segment depression or even no ST changes has been reported, this is very uncommon. In Patient 1, the presence of tachycardia along with ST-segment depression raises the possibility of Syndrome X (angina-like chest pain with ST-segment depression, no demonstrable myocardial ischaemia and normal coronary arteries,5 which is not to be confused with the endocrinological Syndrome X, or insulin resistance metabolic syndrome6 ). Another possible explanation is the coronary "slow flow" phenomenon, which may be caused by microvascular spasm, although slow flow was not mentioned in the angiography report. Nevertheless, the complete resolution of angina in Patients 1 and 3 after treatment with amlodipine provides circumstantial evidence that spasm was involved. Radionuclide studies shed some light on a possible link between mental stress and coronary vasoconstriction. Subjects exposed to minor experimental stress have been shown to develop significantly reduced coronary perfusion and ischaemic abnormalities of left ventricular wall motion. These abnormalities are due to coronary vasoconstriction, but are limited to subjects with at least minor degrees of underlying coronary artery disease, and are more pronounced when this disease is more severe. Subjects with normal arteries do not show such changes.7 Similarly, coronary spasm in the setting of emotional problems was described in nine women with normal or near-normal arteries,8 but it was likely that most had at least minor atherosclerosis (ie, <25% narrowing). In two of the patients reported by Mansour et al, coronary vessels were normal (and possibly also in Patient 2 before occlusion), so induction of spasm or vasoconstriction with ischaemia seems inconsistent with the experimental studies. However, angiographically "normal" arteries may harbour minor atherosclerotic lesions that do not encroach on the lumen. In addition, the severe and overwhelming emotional stress and arousal typical of panic, which these patients doubtless experienced, contrasts with the relatively minor tasks with minimal emotional responses to which the experimental subjects were exposed. The coronary vascular responses to severe and minor stress may be quite different. For example, extreme rage induced myocardial infarction in dogs, although after a critical stenosis had been created in a coronary artery.9 Severe emotional arousal deserves further investigation. Wilkinson et al showed that patients with panic disorder have dramatic increases in epinephrine secretion and cardiac epinephrine spillover during panic, but that baseline levels and responses to mild experimental stress differ little from those of control subjects.10 Cardiac perfusion and functional studies during panic would be of interest, but would require panic attacks to be artificially induced in the laboratory. The absence of ECG changes in Patient 3, despite severe chest pain and significantly raised cardiac enzyme levels, raises an important issue about myocardial ischaemia. In the radionuclide studies mentioned above, significant decreases in perfusion or abnormalities in wall motion often occurred without ischaemic pain or ECG changes. Ischaemia can be electrocardiographically "silent", particularly in certain vascular distributions, such as that of the left circumflex coronary artery. Nevertheless, it must be unusual that ischaemia sufficient to produce necrosis should produce no ECG changes. These cases should raise clinician awareness of the potential association between severe anxiety and myocardial ischaemia, so that patients with chest discomfort and panic disorder are appropriately investigated. All patients with severe panic accompanied by prolonged chest pain should have cardiac enzyme levels measured, irrespective of ECG findings. While epicardial coronary artery spasm is a plausible explanation, further investigations are needed into the mechanisms of ischaemia in panic disorder. S Ben Freedman Professor, and Head, Department of Cardiology Concord Repatriation General Hospital, University of Sydney, NSW Christopher C Tennant Professor and Head, Department of Academic Psychiatry Royal North Shore Hospital, University of Sydney, Sydney, NSW Mansour VM, Dominic JC, Jennings GL, et al. Panic disorder: coronary spasm as a basis for cardiac risk? 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