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Department of Cardiothoracic Surgery, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
(Email: alexander.kogan{at}sheba.health.gov.il).
We are grateful to Dr Heitz [1] for indicating these reports of the occurrence of Takotsubo syndrome after cardiac operations, and for commenting on our article [2].
We agree with him that the cause of this syndrome is still not established. Even observed commonality in age and gender is not reliable, because it has been reported in the very young and in males. No common pathway in the pathogenesis has yet been elucidated. A wide variety of additional triggering factors have been described, including onset or exacerbation of diseases such as cerebrovascular accident, hypoglycemic attack, hyperthyroidism, asthma, acute abdomen, frequent epinephrine medication, pneumothorax, myasthenic crisis, as well as ingestion of the quinolone antibiotic levofloxacin and the nonsteroidal anti-inflammatory agent loxoprofen.
Cardiac biomarkers including troponin and brain natriuretic peptide are usually mildly elevated, as reported in 86.2% of the patients. Elevated norepinephrine concentration was reported in 74.3% of the patients [3].
Although the typical pattern of left ventricular (LV) dysfunction can be well delineated by noninvasive imaging techniques such as echocardiography or magnetic resonance imaging (MRI), early coronary angiographic examination is highly recommended to reliably rule out acute myocardial infarction.
Additional imaging tests reveal potentially more specific disease features than echocardiography or MRI, but are more useful to study the pathophysiology than for decision making. In 23I-β-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, decreased uptake of apex is seen in the acute phase. Scintigraphy with 123I-metaiodobenzyl guanidine (MIBG) can also reveal transient dysfunction of the cardiac catecholamine dynamics. Impairment of cardiac neuronal uptake of 123I-MIBG based on a reduction of the heart-to-mediastinum uptake ratio depicts the unique pattern of ventricular asynergy and indicates the existence of cardiac sympathetic hyperactivity, with maintained coronary blood flow. Technetium-99m (99mTc)-tetrofosmin myocardial single-photon emission computed tomography demonstrates normalization of uptake after 14 days, with an improved coronary flow reserve improved after 30 days.
Positron emission tomography (PET) with 13N-ammonia and 18F-fluorodeoxyglucose within the first 72 hours of presentation shows reduced myocardial glucose uptake in the mid-LV and apical myocardial segments, which is out of proportion to perfusion abnormalities in half of the patients. Delayed hyperenhancement on gadolinium-enhanced cardiovascular magnetic resonance, which is indicative of active inflammation (eg, myocarditis) or myocardial fibrosis (eg, myocardial infarction), is widely absent in patients with Takotsubo, which usually displays a patchy subepicardial pattern. Right ventricular involvement has been reported to be common in Takotsubo. It seems to be associated with a more severe impairment in LV systolic function and may show similar abnormal wall motion with a pressure gradient [4]. Dynamic intraventricular obstruction may perpetuate apical ballooning, at least in patients with an intraventricular pressure gradient between the LV apex and the base. Follow-up cardiac catheterization after 16 days usually shows normal wall motion without pressure gradients. Most patients who survived the first 48 hours experienced steady complete recovery, and heart function was found to be normal in follow-up echocardiography within a few weeks [5]. Contrary to conventional wisdom, this is not a benign disease: Complications occur in 18.9% and death in 3.2% [6] due to left ventricular free wall rupture, ventricular septal perforation [7], and arrhythmogenic sudden death [6]. The most common reported serious complications are cardiogenic shock, followed by LV thrombus formation, congestive heart failure [8], left ventricular outflow tract obstruction, pulmonary edema, stroke with apical thrombus formation, and acute pericarditis.
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