Two Different Mechanisms of Myocardial Ischemia Involving 2 Separate Myocardial Segments in a Patient With Normal Coronary Angiography
A 53-year-old woman with no risk factors was admitted to our hospital in December 2006 because of worsening angina and positive exercise stress test. Two months earlier, she had been admitted to another hospital because of prolonged epigastrial pain without radiation, which had subsided just before she reached the hospital, that was associated with diagnostic elevation of troponin; she reported 3 episodes of the same pain lasting ≈5 minutes in the early morning hours over the preceding 3 weeks. A few hours after admission, she had a recurrence of pain with ST elevation on the inferior electrocardiogram (ECG) leads that responded to intravenous nitrates. Subsequent angiography failed to show lumen stenosis, irregularities, and thrombus deposition, but ventriculography showed akinesia of the basal inferior wall. The discharge diagnosis was inferior ST-elevation myocardial infarction (creatine kinase-MB peak, 112 U/L; troponin I peak, 9.74 ng/mL) with normal coronary arteries, and she was prescribed aspirin, calcium, antagonists, and β-blockers.
She remained symptom free for about a month. Then, during a very stressful period of her life, she began to present with anginal pain during effort, sometimes on emotion. She insisted that the features of this new pain were completely different from those of the attacks leading to the previous hospital admission; this pain was located behind her upper sternum and radiated to the neck and ulnar side of the left arm. It did not subside promptly with the termination of exercise but lasted 5 to 15 minutes, with a poor response to nitroglycerine. The ECG stress test was positive, with 2-mm ST-segment depression in leads V2 through V6, and a repeated angiography showed normal coronary arteries. Despite an increased dosage of β-blockers (atenolol 100 mg), the symptoms did not improve.
On admission to our hospital, the patient was asymptomatic, and her physical examination was unremarkable. The ECG showed small Q waves in leads II, III, and aVF. An echocardiography dipyridamole test (0.56 mg/kg in 4 minutes) caused exactly the same type of chest pain that had brought her to the hospital and showed it to be associated with diagnostic ST-segment depression in leads V2 through V5 (Figures 1 and 2⇓) without changes in regional wall motion (Movie I in the online-only Data Supplement). Cardiac magnetic resonance showed subendocardial hypoperfusion of the anterior wall on perfusion imaging performed during dipyridamole infusion (Figure 3) and delayed subendocardial enhancement indicative of myocardial necrosis in the basal inferior wall (Figure 4). Methylergometrine maleate testing (0.15 mg IV) caused akinesia of the midcavity inferior and inferoseptal walls (Movie II in the online-only Data Supplement) associated with transient 2-mm ST elevation in leads II, III, and aVF, observed by continuous ECG monitoring but not recorded, and epigastrial pain, identical to the pain that led to her first hospitalization, which was promptly relieved by intravenous nitrate administration.
Thus, this patient presented characteristic features of anginal pain consistent with 2 distinct coronary ischemic mechanisms involving 2 separate segments of the ventricular wall. This conclusion is supported by the response to the provocative stressors dipyridamole and methylergometrine: microvascular dysfunction causing anterior wall ischemia (associated with upper sternal chest pain radiating to the left arm typically brought about by effort that is long-lasting and poorly responsive to nitroglycerine but without detectable contractile abnormalities) and inferior wall ischemia caused by coronary spasm (associated with regional contractile dysfunction and the same epigastric pain typically occurring spontaneously at rest).
Anginal pain with distinct locations and radiation was reported by ≈25% of patients when adenosine, a powerful algogenic stimulus, was injected separately into the left and right coronary arteries.1 Thus, the site of ischemia in this patients may account for the different localization and irradiation of pain.
The use of appropriate tests and the integration of the pathophysiology information derived from each noninvasive stress test performed allowed us to confirm the clues provided by the features of anginal pain by a patient who sounded like a reliable historian.
In patients with recurrent exertional chest pain and normal coronary arteries, the occurrence of chest pain and ECG ST depression associated with normal or hyperkinetic left ventricular wall motion during vasodilatation test suggests myocardial ischemia caused by coronary microvascular dysfunction.2 The patchy distribution and the limited transmural extension of the perfusion defects, determined by dysfunction of small resistance coronary artery vessels (<500 μm), may explain the absence of regional wall motions abnormalities.3 Cardiac magnetic resonance, a high-sensitivity technique, allows demonstration of the subendocardial ischemia4 and the old myocardial necrosis by late gadolinium enhancement.
We believe that in the era of “one-size-fits-all” management strategies, the “revival” of medical history should be encouraged because it may suggest specific pathogenetic mechanisms.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/121/1/e1/DC1.
Lanza GA, Buffon A, Sestito A, Natale L, Sgueglia GA, Galiuto L, Infusino F, Mariani L, Centola A, Crea F. Relation between stress-induced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X. J Am Coll Cardiol. 2008; 51: 466–472.