Apical ballooning in patients with coronary artery disease versus takotsubo cardiomyopathy—A case control study

Abstract

Takotsubo cardiomyopathy (TC) tends to mimic acute coronary syndrome (ACS) in its clinical presentation. The most common mode of presentation of TC is chest pain or dyspnea precipitated by physical or emotional stress and accompanied by EKG changes (Twave inversion, QT prolongation, transient anteroseptal Q wave, ST segment changes) and elevation of cardiac enzymes [1]. Previous studies have indicated a distinct biochemical marker profile (CK, CKMB, troponins, myoglobin, BNP) in TC and ACS [2–5]; however, data on the differences between TC and LV apical ballooning associated with CAD is sparse. In the present studywemade an attempt to identify unique features differentiating the two conditions. We identified all patients with ‘apical ballooning’ who presented with chest pain. The patients were investigated for ACS, from our echo database (1999–2010—a total of N50,000 records). We then identified those with non-obstructive CAD and other typical findings of takotsubo disease as per the modified Mayo Clinic criteria and defined them as the ‘case’ group (T) (n=11) [6]. From the same database we identified the patients with apical ballooning and obstructive CAD on angiography (N/=50% stenosis of left main coronary or N/=70% stenosis of any coronary with diameter of 2 mm or more). We confirm the arteriographic findings by review of the original images. We selected age, sex and ejection fraction matched controls (C) in a 1:1 ratio (n=11) from that group (baseline features, Table 1); and compared biomarkers as well as echo findings (extracted in duplicate with mean readings included to eliminate interobserver variability) to identify differentiating features between the two groups. All biomarkers were drawn within 24 h of admission and the methods for estimating the levels of various biomarkers did not change during the course of the study. Continuous variables were compared using means; while discrete variables were expressed as ‘percentages’ for comparison using T test. All analyses were performed using Stata Ver 11. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. Patients with true takotsubo had significantly higher inflammatory markers (neutrophil count, hsCRP); as well as BNP and myoglobin. However ACS patients had higher troponin levels and acute valvular disease (acute decompensation of valvular function from baseline, i.e., valvular incompetence) was more prevalent (Table 2). Our results show that the higher levels of BNP, inflammatory markers (leukocyte count, neutrophil/lymphocyte ratio, hs-CRP) and serum myoglobin in TC might be able to differentiate TC from LV apical ballooning associated with CAD in a non invasive way. In our study, the levels of BNP and myoglobin were considerably higher in TC as compared to CAD even though the degree of myocardial damage and necrosis was less in TC. Our results are in consensus with previous studies which also show elevated levels of BNP in TC patients [3,5,7]. Regional wall stress secondary to observed basal hyper contractility in TC could be the reason behind the associated high levels of BNP and myoglobin [8]. Another important finding in our study is the higher concentration of inflammatory markers in TC which is in consensus with previous studies [2,9–14]. The difference in pathogenesis of LV apical ballooning associated with CAD and TC could explain our findings, with the latter being predominantly an inflammatory process. The role of inflammation in TC has been established on endomyocardial biopsies and has been supported by elevated levels of various serological and radiological markers (T2 ratio, global relative enhancement) of inflammation; but whether this inflammation is a primary phenomena or secondary to sympathetic overdrive, viral infection or microvascular obstruction, still remains unclear [2,9–15]. Our study has few important limitations. Similar to previous studies, it is a single center study and has a small sample size, so extrapolation of findings to other study populations should be performed with caution. Our control group has a much higher prevalence of functional valvular heart disease (81.8% vs. 9.1%), whichmay act as a confounding factor, thus it may be possible that the actual difference in the level of marker of wall stress like BNP may be even higher between the two groups. Another limitation is that we do not have data on othermarkers of inflammation, especially markers of platelet and monocyte activity and interleukins levels which have been shown to be helpful in differentiating ACS/CAD and TC in previous studies. Our results show that higher inflammatory markers as well as elevated BNP and serum myoglobin can differentiate TC from LV apical ballooning associated with CAD without ICA and may have important clinical implications in subsets of patients who are at higher risk of developing ICA related complications. Further large scale prospective studies are required to establish the role of inflammatory marker, BNP and myoglobin in the diagnostic algorithm of TC in different clinical settings.