Left Anterior Descending Coronary Artery Stenosis

Abstract

Takotsubo cardiomyopathy is characterized by chest pain, electrocardiographic abnormalities such as ST-segment elevation or depression, and elevated cardiac enzyme levels. Left ventriculography reveals transient akinesis of the involved segment of the myocardial wall (usually the left ventricular apex) and compensatory hyperkinesis of the noninvolved myocardium, which appears as apical ballooning during systole. Existing criteria for the diagnosis of takotsubo cardiomyopathy include the absence of obstructive coronary artery disease. Indeed, previous investigators have found incidental stenosis in only a minority of patients.

Herein, we present the unusual case of an 84-year-old woman who sustained 4 episodes of takotsubo cardiomyopathy in 18 years. At the time of the initial episode, coronary angiography revealed no substantial stenosis. Concomitant with the 2nd episode, stenosis in the 1st obtuse marginal branch was treated with stenting. No new lesions were apparent after the patient's 3rd presentation, and the previously placed stent was patent. During the 4th (current) presentation, we detected and percutaneously treated severe stenoses in the patient's left anterior descending coronary artery and 2nd obtuse marginal branch.

Although this report is of a single patient only, it definitively illustrates that severe coronary artery disease can occur in patients who have takotsubo cardiomyopathy. We recommend the thorough evaluation of possible coronary artery disease in high-risk patients, even upon the strong clinical suspicion of takotsubo cardiomyopathy.

Takotsubo cardiomyopathy was first reported in the Japanese population. It occurs predominantly in postmenopausal women, and episodes seem to be preceded by emotional or psychological distress.¹ The pathophysiology of this disease remains unknown; however, excessive sympathetic activity and abnormal catecholamine dynamics might have a major role in the pathogenesis of takotsubo cardiomyopathy.^2,3 Takotsubo cardiomyopathy can be thought of as a neurocardiogenic disorder that manifests itself as transient left ventricular (LV) dysfunction due to excessive catecholamines.³ Herein, we present an unusual case of a woman with takotsubo cardiomyopathy and coexisting severe coronary artery disease (CAD).

Case Report

In 2010, an 84-year-old woman emergently presented with chest pain, which was partially relieved by nitroglycerin. Her family reported that she had been emotionally distressed 2 days prior, on the anniversary of her husband's death. She had experienced a similar episode in 1992, presenting with chest pain; on angiography, her coronary arteries had shown no severe stenosis. Although it was not recognized at the time, the LV apex showed akinesis that was consistent with takotsubo cardiomyopathy. She had no further cardiac problems until 1999, when she again had chest pain. Due to ST-segment elevation in leads I and aVL on electrocardiography (ECG), angiography was repeated. It showed severe stenosis of the 1st obtuse marginal branch (OM) with Thrombolysis in Myocardial Infarction (TIMI)-3 flow; this was treated by means of percutaneous coronary intervention. The left ventriculogram showed apical hypokinesis that was consistent with takotsubo cardiomyopathy, in that the regional wall-motion abnormality did not correspond with the region of the stenosed coronary artery; however, that diagnosis was not considered at the time, in part because takotsubo cardiomyopathy had not yet been widely recognized in the medical literature. Subsequent echocardiography revealed that the patient's LV function had returned completely to normal. In 2003, she had a 3rd episode of chest pain, after a family quarrel. At that time, a left ventriculogram showed moderate LV dysfunction with apical akinesis, again consistent with takotsubo cardiomyopathy. The OM stent was patent, and no new lesions had developed since the earlier angiography. An echocardiogram 2 months later showed complete recovery of LV function and no regional wall-motion abnormalities.

At the current presentation—the patient's 4th episode with chest discomfort—ECG showed new, diffuse ST-segment elevation in the anterolateral and inferior leads (Fig. 1A) when compared with a routine ECG from a year earlier (Fig. 1B). Laboratory studies showed that cardiac enzyme levels were mildly elevated: the cardiac troponin T value was 0.13 ng/mL (normal, ≤0.03 ng/mL), and the MB fraction of creatine kinase was 43.7 ng/mL (normal, ≤6.1 ng/mL). In view of the ST-segment elevation and the patient's known CAD, angiography was emergently performed. A left ventriculogram showed LV apical ballooning typical of takotsubo cardiomyopathy (Figs. 2A and 2B). The left anterior descending coronary artery (LAD) had a 90% stenosis in the mid portion, with TIMI-2 distal flow (Fig. 2C). In addition, the 2nd OM had an 80% proximal stenosis with TIMI-3 flow (Fig. 2D). The previously stented 1st OM was open, with minimal restenosis. Intracoronary nitroglycerin was not given during the procedure.

Fig. 1 A) Electrocardiogram shows new ST-segment elevation in the precordial leads (V₂ through V₆) and inferior leads (I, II, and aVF). B) Normal electrocardiogram, recorded 1 year earlier.

Fig. 2 Left ventriculograms in A) systole and B) diastole. The arrow shows apical ballooning, a takotsubo pattern of contraction of the left ventricular apex, in systole. Coronary angiograms show the areas of stenosis (arrows) in C) the left anterior descending coronary artery (LAD) and D) the 2nd obtuse marginal branch (OM2).

The patient underwent successful stenting of the LAD and the 2nd OM. Echocardiography showed akinesis of the mid and apical portions of the LV and a decrease in ejection fraction to 0.35, consistent with takotsubo cardiomyopathy (Figs. 3A and 3B). The patient's hospital course was complicated by a transient ischemic attack secondary to carotid artery disease. Upon her discharge from the hospital after a 9-day stay, her LV ejection fraction had increased to 0.45, and the regions of the myocardium that were previously akinetic had improved (Figs. 3C and 3D). Eighteen months later, she had experienced no further episodes and was doing well.

Fig. 3 Echocardiograms (apical 4-chamber views) at the patient's initial evaluation show apical ballooning in A) systole (arrows) and B) diastole. Echocardiograms upon the patient's hospital discharge show improved apical wall motion in C) systole (arrow) and D) diastole. LA = left atrium; LV = left ventricle; RV = right ventricle

Discussion

The pathogenesis of takotsubo cardiomyopathy is not well understood. The results of various studies have suggested several causes, including excessive sympathetic activity, coronary vasospasm, microvascular dysfunction, plaque rupture, and thrombosis with spontaneous recanalization.^1,3–7 No epicardial obstruction during immediate angiography was reported by those investigators. In 1 study,⁵ provocable vasospasm was confirmed in only 21% of the cases. Most current evidence suggests that catecholamine excess with resultant microvascular dysfunction is the most likely pathogenic mechanism in takotsubo cardiomyopathy.1,3,4,6,8

Although criteria proposed by the Mayo Clinic require the absence of obstructive CAD for a diagnosis of takotsubo cardiomyopathy,^1,4 Kurisu and colleagues⁹ reported incidental CAD in 10% of Japanese patients with takotsubo cardiomyopathy. More important, 6% of patients with takotsubo cardiomyopathy had CAD (defined as a >75% decrease in luminal diameter) in non-wraparound LADs,⁹ which was considered to be an incidental finding. Takotsubo cardiomyopathy and CAD need not be mutually exclusive, because patients with this cardiomyopathy are typically postmenopausal or elderly and are therefore likely to have several risk factors for CAD. In addition, the presence of severe CAD does not necessarily exclude the diagnosis of takotsubo cardiomyopathy, provided that the distribution of the obstructive disease does not directly correspond with the zone of ventricular dysfunction.¹⁰ Of note, it is difficult to determine whether takotsubo cardiomyopathy is present in the setting of severe LAD disease, given that the apex is involved in both conditions. However, in patients with takotsubo cardiomyopathy (such as our patient), the extent of regional wall-motion abnormality is usually greater than it is in patients who have disease in the non-wraparound LAD.¹¹

Our case is also very unusual in that a 4th episode of takotsubo cardiomyopathy occurred in a patient who was incidentally found to have progressive CAD. Elesber and associates¹² reported a 4-year recurrence rate of 11.4% in 100 unselected patients who had takotsubo cardiomyopathy.

To our knowledge, this is the only report of 4 takotsubo cardiomyopathy episodes in the same patient during a span of 18 years. In addition, this case underscores the need for a thorough evaluation of concomitant CAD in high-risk patients, even if there is a high clinical suspicion of takotsubo cardiomyopathy. Future studies are needed to improve the criteria so that takotsubo cardiomyopathy can be differentiated from an acute coronary syndrome without the aid of invasive coronary angiography.