Why does angina cause fatigue? 

Angina by definition is a transient Ischaemic  episodes not leading to  cellular death. As  such it should not cause chronic fatigue. However, during an anginal episode, if the ischaemic territory is large enough or if critical component of the heart are involved (e.g. Papillary muscles and mitral valve), then it may be associated with fatigue and/or shortness of breath

Can you describe the relationship between CAS, CMVD and Endothelial Dysfunction?

Myocardial ischaemia has been traditionally perceived as the consequence of atherosclerotic obstructions of the coronary vessels. More recently an overwhelming body of evidence has proven that atherosclerotic obstructions are just one of several mechanisms that can precipitate myocardial ischaemia. CAS, CMVD and Endothelial Dysfunction are included among the mechanisms that, in isolated fashion or in combination, may cause myocardial ischaemia

What is the difference between Endothelium Dependent CMD and non Endothelium Dependent CMD?

The wall of the blood vessel (coronary artery) supplying the heart muscle has got three layers: the innermost layer contains endothelial cells, the middle layer contains the smooth muscle cells and the outermost layer contains collagen fibres for support.

The endothelial cells naturally release a substance called nitric oxide (NO), that then diffuses along into the neighbouring smooth muscle cells and causes these cells to relax. This leads to the coronary artery dilating, which results in an increased blood flow to the heart muscle. This is an important physiological response to exertion.

Endothelium-dependent CMD essentially means an inability of the endothelial cells to produce nitric oxide. As a result, the smooth muscle cells are unable to relax and the coronary artery is unable to dilate as required. This results in blunted increase in blood flow to the heart muscle during times of stress, which results in angina.

Endothelium-independent (or non-endothelium dependent) CMD refers to an inability of the smooth muscle cells to relax despite an adequate amount of nitric oxide. This, again, results in blunted increase in blood flow to the heart muscle during times of stress, which results in angina.

Therefore, both group of patients have an inability to dilate their coronary arteries in response to stress, which reduces the blood flow to the heart muscle during times of stress, leading to angina