Usefulness of myocardial positron emission tomography/nuclear imaging in Takotsubo cardiomyopathy

Abstract

AIM:To analyse and summarize all the articles related to positron emission tomography and Takotsubo cardiomyopathy (TTC). METHODS:We performed a systematic review of the existing literature on positron emission tomography/ nuclear imaging and Takotsubo cardiomyopathy using PUBMED database. We combined search terms such as "takotsubo", "takotsubo syndrome", "myocardial positron emission tomography", "positron emission tomography". All case reports were excluded. The list included only four articles which were reviewed by two independent investigators. It was not possible to undertake a formal meta-analysis because of the heterogeneity of the studies; therefore, we made a narrative synthesis of the collected data. RESULTS:Nuclear medicine techniques can be useful employed in the differential diagnosis of TTC from an acute coronary syndrome (ACS). In fact, transient left ventricular (LV) apical ballooning is a syndrome frequently misdiagnosed as an ACS and can mimic symptoms of myocardial infarction with ST-T segments changes on electrocardiography (ECG), a limited release of myocardial enzyme, mainly reported after sudden emotional or physical stress, and an akinesis or dyskinesis of the left ventricle apex which are completely reversible in a few weeks. In the studies included in this review, nuclear medicine techniques have demonstrated a discrepancy between normal perfusion and a reduced glucose utilization in TTC, commonly known as "inverse flow metabolism mismatch". This suggests that apical ballooning represents a transient metabolic disorder on the cellular level, rather than a structural contractile disease of the myocardium, due to a transient decrease of glucose metabolism that might be related to a coronary microcirculation impairment followed by prolonged myocardial stunning. CONCLUSION:Nuclear medicine techniques can be usefully used for the diagnosis of TTC and can increase our knowledge of the pathophysiological mechanisms of TTC. Core tip: Takotsubo cardiomyopathy is a cardiac syndrome with symptoms similar to acute myocardial infarction (MI) including chest pain and electrocardiographic changes, in absence of coronary artery stenosis. This syndrome is characterized by reversible wall-motion abnormalities involving apical and midportion of left ventricle. In the acute phase it is clinically indistinguishable from acute MI but, recently, myocardial positron emission tomography have demonstrated to delineate this syndrome from acute coronary artery disease, also offering a new pathophysiological explanation for this particular syndrome. This clinical review aimed to summarise the most significant experiences on the use of myocardial positron emission tomography in Takotsubo cardiomyopathy. SYSTEMATIC REVIEWS

Tako-Tsubo Stress Cardiomyopathy-A Quantum Event of the Heart?

“…Similarly we cannot rule out microvascular plaque rupture and thrombosis. Positron emission tomography studies using FDG show myocardial stunning in Takotsubo patients, demonstrating transient reductions in glucose metabolism in regions of abnormal systolic function despite relatively intact myocardial perfusion [18]. Similarly, in regions of dysfunction, cardiac MRI demonstrates findings consistent with edema likely due to myocardial inflammation in the acute phases of the disease that resolve with ventricular functional improvement.…”

Plausible speculations on the pathophysiology of Takotsubo syndrome

“…mechanism), leads to a transient regional impairment of myocardial glucose metabolism and innervation, resulting in transient myocardial stunning. I find even more intriguing the authors' speculation [14] that the "severe reduction of FDG uptake in the dysfunctional myocardial segments might be related to a partial volume effect in enlarged, impaired areas", suggesting that partially or totally the impaired glucose utilization may be apparent than real, resulting from the "dilutional effect" on FDG counts (vide infra), of the enlarged afflicted dysfunctional LV regions due to myocardial edema (ME), which has been shown to occur in patients with TTS, by both ECHO, and cardiac magnetic resonance imaging.…”

“…According to the above cited chain of events the apical and mid-ventricular regional contraction abnormalities could be envisaged either as consequent to the basal hypercontractility, or could be thought as occurring as "part and parcel" of the TTS phenotype, along the line previously proposed [2], irrespective of the basal hyperkinesis, as an evolutionary adaptive cardioprotective response to the heightened intracardiac systolic stretch [2,9,15]. Thus, ME could be viewed as a consequence of this relentless systolic myocardial stress, and may be playing a modulating effect on the diagnoses of "myocardial ischemia" or "metabolic glucose impairment", detected by imaging modalities, which may be partially (doubt, totally) due to a "partial volume" effect, as discussed above [14]. Variations in the results from imaging testing, described in different studies, could be attributed to the timing of their performance and the stage of the illness of different patients tested.…”

“…The authors of the review [14] speculated that the heretofore unexplained severe reduction of FDG uptake in the dysfunctional LV myocardial segments, associated with an overlapping pattern of severe denervation, both of which were ameliorated and even normalized in the follow-up after the improvement of myocardial function, might be related to a specific metabolic impairment of the glucose utilization in the presence of normal perfusion ("inverse flow metabolism mismatch"), constitute a transient metabolic disorder on the cellular level (functional), rather than a structural contractile disease of the myocardium, that might be related to a coronary microcirculation impairment, followed by prolonged myocardial stunning. In other words the authors felt [14] that the transient microcirculation impairment (? mechanism), leads to a transient regional impairment of myocardial glucose metabolism and innervation, resulting in transient myocardial stunning.…”

“…A recent review, based on the only 4 available clinical studies of imaging testing in patients with TTS [14], summarized the information on: 1) myocardial perfusion, employing single photon emission computed tomography (SPECT) or positron emission tomography (PET) scanning, and Thallium-201, nitrogen 13-ammonia, and 99 mTc-tetrofosmin as radiotracers, which showed a range of findings, consisting of normal myocardial perfusion at rest, a slight reduction in tracer uptake after adenosine in the apex and apical segments of the left ventricle (LV) that normalized at rest, significant reduction of myocardial blood flow and coronary flow reserve in the apical segments in comparison to the mid-ventricular and basal LV segments, and a decreased radiotracer uptake in only a small area of the apex, with complete restoration of normality at follow-up imaging, 2) myocardial glucose metabolism, employing myocardial PET using fluorine 18 fluorodeoxyglucose (FDG), which showed severe and diffuse reduced 18F-FDG uptake in the LV, with the extension of the metabolic defect being much larger and more severe than the perfusion defect with 201 Tl SPECT imaging in the acute phase of TTS, with recovery at follow-up after the normalization of the LV function; 3) assessment of myocardial innervation, employing myocardial 123 I-metaiodobenzylguanidine (mIBG) SPECT, which disclosed a severe reduction/absence of mIBG uptake (denervation) in the normally perfused but dysfunctional segments of apical or mid-ventricular LV regions, with overlapping defects of myocardial glucose metabolism and myocardial denervation, and repeated 123 I-mIBG SPECT six months after acute symptoms, demonstrating an improvement of tracer uptake or complete normalization of innervation in the LV apical segments. The authors of the review [14] speculated that the heretofore unexplained severe reduction of FDG uptake in the dysfunctional LV myocardial segments, associated with an overlapping pattern of severe denervation, both of which were ameliorated and even normalized in the follow-up after the improvement of myocardial function, might be related to a specific metabolic impairment of the glucose utilization in the presence of normal perfusion ("inverse flow metabolism mismatch"), constitute a transient metabolic disorder on the cellular level (functional), rather than a structural contractile disease of the myocardium, that might be related to a coronary microcirculation impairment, followed by prolonged myocardial stunning.…”