Up to half of those who suffered a myocardial infarction do not reach hospitals because of an early cardiac arrest due to ventricular fibrillation (VF). Survivors who had a coronary angiogram include a group of young men with history of smoking with patent coronary arteries. They exhibit generalised endothelial dysfunction, in response to acetylcholine; they develop epicardial vasospasm with failure of coronary flow to increase by 50% from baseline, despite preserved vasodilatory capacity to adenosine hyperaemia. This chapter presents detailed coronary physiology study of four VF cases, one woman from coronary artery thrombotic occlusion and three men with coronary artery spasm, one due to thyrotoxicosis, who had acetylcholine challenge at index admission and following treatment 1 year later. In this case, there was a biphasic, initial vasoconstrictive and blunted flow response to low-dose acetylcholine, followed by profound vasodilatation with tripling of flow rate that was slow with high-dose acetylcholine. This speculatively could be due to shifting of suppressed endothelial muscarinic nitric oxide pathway, through the same M₃ receptor to endothelial-derived hyperpolarising factor (EDHF) via Ca2+-activated K+ channel-mediated hyperpolarisation of the vascular smooth muscle cells (VSMC) across the myoendothelial gap junctions. This natural and endogenous calcium channel blockade if augmented could explain why calcium channel blockers might have less added value in some patients with coronary microvascular dysfunction, and this could potentially be tested if intracoronary verapamil’s flow response is blunted with continuous thermodilution. Finally, the last two patients who had VF coincidentally shared a syndromic triad of left ventricular mid-wall fibrosis, benign early repolarisation and right coronary artery spasm, which surprisingly are pathophysiologically coherent.