The precise cause of takotsubo cardiomyopathy (TC) remains controversial. Plaque rupture with transient thrombotic occlusion of a transapical left anterior descending coronary artery (LAD) has been advanced as a potential mechanism. To explore this hypothesis, the investigators analyzed data from 11 patients prospectively enrolled in the Rhode Island Takotsubo Cardiomyopathy Registry who underwent coronary angiography and intravascular ultrasound evaluation of the LAD during their initial presentation. Despite the presence of nonobstructive coronary artery disease, no culprit lesion was identified in any patient. Similarly, the course of the LAD failed to account for the characteristic left ventricular apical ballooning seen in TC. In conclusion, an atherosclerotic coronary lesion in the LAD causing an aborted myocardial infarction may not be the primary underlying cause of TC, and nonobstructive coronary artery disease and TC may coexist without a direct causal association.
The pathogenesis of takotsubo cardiomyopathy (TC) is still not well understood. The leading proposed mechanism involves catecholamine-induced microvascular spasm or dysfunction. Transient thrombotic occlusion of a large, transapical left anterior descending coronary artery (LAD) causing an aborted myocardial infarction (MI) has also been considered as a possible cause. The Mayo criteria by Bybee et al require the absence of significant coronary artery disease (CAD) to diagnose TC. Although evidence of concurrent nonobstructive CAD has been noted in several studies, Ibanez et al reported evidence of culprit atherosclerotic lesions in 5 patients presenting with TC. To test the hypothesis that underlying nonobstructive CAD in the LAD could be the cause of TC, we analyzed angiographic and intravascular ultrasound (IVUS) data for 11 patients enrolled in the Rhode Island Takotsubo Cardiomyopathy Registry.
Methods
The Rhode Island Takotsubo Cardiomyopathy Registry prospectively enrolled patients presenting with acute coronary syndromes at 2 major teaching hospitals in Rhode Island who underwent emergent cardiac catheterization and fulfilled Mayo diagnostic criteria for TC. Informed consent was obtained as outlined in the institutional review board–approved protocol. The clinical characteristics and 4-year outcomes of the initial 70 patients have been published previously. Since the reporting of the original registry data in April 2008, an additional 14 patients have been enrolled. Of these 84 patients, 11 nonconsecutive patients underwent IVUS examination of the LAD if nonobstructive CAD (defined as <40% diameter stenosis by visual estimation) was identified at the time of initial coronary angiography. The precise degree of LAD stenosis was subsequently evaluated by quantitative coronary angiography.
IVUS examination was performed using Boston Scientific Corporation (Natick, Massachusetts) equipment. Intracoronary nitroglycerin was administered before advancing the IVUS catheter to the distal LAD, and automatic catheter pullback was performed at a standard 0.5 mm/s. To assess for corresponding wall motion abnormalities, coronary angiographic and left ventriculographic images were overlaid and used to trace the entire course of the LAD on the same projection.
Analysis of angiographic and IVUS data—including the presence of intracoronary thrombus, dissection, plaque rupture, ulceration, spasm, or distal embolization—was performed by 1 of a group of 4 experienced interventionalists blinded to other patient data. In agreement with previously published criteria, plaque rupture was defined as plaque containing a cavity that communicates with the coronary lumen with an overlying residual fibrous cap fragment. Plaque ulceration was defined as a small crater consisting of a discrete luminal widening with associated luminal irregularity.
Results
Over the course of 6 years, from July 2004 to July 2010, 11 patients underwent simultaneous angiographic and IVUS examinations. Their clinical, angiographic, and IVUS characteristics are listed in Table 1 . All patients underwent catheterization <24 hours after admission. Typical takotsubo left ventricular apical ballooning was present in all patients. Morphologic variants, such as “apical sparing” and “reverse” takotsubo, were excluded. All patients were women, with a median age of 69 years, and 73% of patients had ≥1 traditional cardiovascular risk factor. The most common presenting symptom was chest pain, and precipitating stressing events were identified in 64% of patients. The median ejection fraction at initial angiography was 30% (interquartile range [IQR] 25% to 35%), and the median peak troponin I level during the course of hospitalization was 3.1 ng/ml (IQR 1.3 to 6.1).
| Patient | Age (Years)/Gender | Presenting Symptom | Precipitating Event | CV Risk Factor | Initial ECG Findings | Peak TnI (ng/ml) | LVEF (%) | Maximal LAD Stenosis (%) | MLA (mm 2 ) | CSA Stenosis (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 43/F | Chest pain | Emotional | HTN | STE | 3.5 | 45 | 36 | 12.2 | 36 |
| 2 | 51/F | Chest pain | Emotional | HTN | TWI | 2.7 | 30 | 32 | 4.9 | 39 |
| 3 | 58/F | Syncope | Emotional | HTN | STE | 10.0 | 25 | 25 | 6.3 | 52 |
| 4 | 61/F | Chest pain | None | None | STE | 5.6 | 25 | 38 | 2.6 | 32 |
| 5 | 65/F | Chest pain | None | HTN, HLD | TWI | 1.1 | 30 | 37 | 6.0 | 39 |
| 6 | 69/F | Syncope | Physical | None | STE | 0.3 | 45 | 29 | 4.9 | 37 |
| 7 | 73/F | Dyspnea | Physical | HLD | TWI | 0.8 | 30 | 20 | 8.1 | 34 |
| 8 | 74/F | Chest pain | Emotional | HTN | STE | 12.8 | 25 | 29 | 15.7 | 28 |
| 9 | 79/F | Chest pain | Physical | HTN | LBBB | 3.1 | 20 | 34 | 7.2 | 35 |
| 10 | 83/F | Chest pain | None | None | STE | 6.7 | 25 | 33 | 17.3 | 43 |
| 11 | 84/F | Syncope | None | HTN | TWI | 1.6 | 40 | 35 | 6.2 | 23 |
All patients had mild nonobstructive CAD by coronary angiography and IVUS. Median maximal LAD stenosis was 30% (IQR 20% to 32%) by visual estimate and 33% (IQR 29% to 36%) by quantitative coronary angiography. IVUS demonstrated a median luminal area in the LAD of 6.2 mm 2 (IQR 5.5 to 10.1) and a median cross-sectional area stenosis (external elastic membrane area divided by luminal area) of 36% (IQR 33% to 39%). Neither angiographic nor IVUS examination of the LAD revealed any evidence of unstable intracoronary lesions, plaque rupture, thrombus fragments, or features suggestive of distal embolization.
Figure 1 depicts a representative left ventriculogram showing the prototypical apical ballooning seen in TC and a superimposed angiogram of the same patient’s LAD in the same projection.
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