Stress can literally break the heart. This was called neurogenic cardiomyopathy with its distinctive widespread giant inverted T-wave on electrocardiogram (ECG) of subarachnoid haemorrhage sufferers in the 1950s. Hikaru Sato of Hiroshima set up his intracoronary thrombolysis and left ventricular angiography for acute myocardial infarction service in 1981, and two years later he found his first case, characterised by chest pain, unobstructed coronary arteries, and cardiac apical ballooning, akin to the Japanese octopus-trap pot (Takotsubo). Mental trigger occurs in one third of cases, about two percent recur within the year, and postmenopausal women comprise ninety percent of cases. Takotsubo syndrome (TTS) is an acute ischaemic syndrome, typically with a small and salutary troponin leak. If caught early, ECG ST elevation is evident, and coronary angiogram could show multivessel epicardial vasospasm. It is believed that catecholamine surge, causing transient microvascular spasm, with underlying coronary microvascular dysfunction (CMD) causes TTS. However, this would predict a balanced gender distribution. Since the microvasculature, unlike the epicardial coronary artery is less susceptible to atherosclerosis which infiltrates, disrupts and calcifies the vascular media, rendering epicardial vasoconstriction unlikely in older men, but their microvasculature should similarly react like in older women. However, in premenopausal women, oestrogen maintains vascular health, thus preserving compliant, patent, and vasoreactive epicardial coronary arteries. Strangely, coronary artery disease confers protection against TTS. Histologically, TTS is also a form of myocardial stunning. Cardiac abnormalities following TTS are uncommon, but cardiac imaging findings post-TTS reflect concomitant diseases’ effects on the heart, and its prognosis is mainly driven by these, including hypertension, hyperlipidaemia and diabetes. This chapter describes detailed coronary physiology with continuous thermodilution in four women who have had TTS, none of whom has demonstrable CMD, but they uniformly exhibit epicardial endothelial dysfunction which is part of oestrogen-deficient normal ageing, also influenced by lifestyle-related and pre-existing vasoreactive conditions, such as smoking and migraine. One woman displays pre- and post-verapamil acetylcholine-induced coronary slow flow phenomenon (CSFP) with absolute volumetric flow increase, but associated with chest pain and ST depression on ECG. This paradoxical acetylcholine response raises the following four conjectures: 1. Acute CSFP does not equate microvascular spasm; 2. calcium channel blockade is ineffective beyond epicardial vasospasm; 3. non-nitric oxide pathways predominate in the microvasculature; and 4. unimpeded flow and microvascular vasodilatation with subendocardial postcapillary venular exudation cause angina and, if sustained, result in TTS. Cardiovascular magnetic resonance (CMR) scan pathognomonically finds scattered myocardial oedema in TTS, akin to chest X-ray and pulmonary oedema. Animal studies show that a three percent rise in myocardial interstitial water content stuns the heart.