Prof Juan Carlos Kaski, St George's, University of London, UK

Juan Carlos Kaski, Professor & Past Director of the Cardiovascular and Cell Sciences research Institute, St George’s University of London, UK, speaks to Cardio Debate about microvascular angina.


Microvascular angina: Which patients are included in this category?
Microvascular angina has been one of the topics of this symposium. It encompasses a relatively large heterogenous group of patients. Essentially what defines microvascular angina is the occurrence of myocardial ischemia in the absence of obstructive coronary artery disease.

In other words patients with microvascular angina come to us with typical chest pain, which suggests coronary artery disease, but when we do an angiogram of these patients we find that the arteries are not occluded at all. But despite this, there is clear evidence for reduction in blood flow that causes the symptoms of angina.

What are the mechanisms?
Microvascular angina can be triggered either by an inability of the micro-circulation to dilate and increase blood flow despite an increase in demand for this blood flow, because the micro-circulation is unable to respond to the appropriate stimuli, and there are many, many reasons for that. The main reason is endothelial dysfunction.

And endothelial dysfunction is associated with a number of traditional, conventional risk factors such as hypertension, dyslipidemia, obesity, the metabolic syndrome, smoking – all of these condition this inability of the microcirculation to respond to ordinary stimuli.

Another important dynamic cause for microvascular angina is microvascular spasm. So, in other words the arteries go into very severe spasm that blocks the blood flow into the heart muscle, and that results in myocardial ischemia. It translates into the symptom of chest pain, but also into electrocardiographic changes suggestive of a reduction in blood flow. In some severe cases the cardiac troponins will go up, indicating that there is damage to the heart muscle cells.

So microvascular angina triggered by these functional mechanisms can go from a relatively trivial condition up to a very severe one that is able to impair function and damage the vessels.

Less commonly, microvascular angina can be triggered by structural mechanisms. The microvessels can, in a way, be trapped by a thickened heart muscle, like in patients with hypertension and left ventricular hypertrophy, people with aortic stenosis with left ventricular hypertrophy, or hypertrophic cardiomyopathy.

In those cases there is a clear organic reason for the coronary microvessels not being able to function normally.

Treating the baseline condition is usually quite effective to relieve the obstruction, or pseudo-obstruction, to the coronary blood flow.

How do you investigate microvascular angina?
Investigation of microvascular angina has been pretty difficult until very recently essentially because these vessels are small in caliber, and therefore are not accessible on angiography. And this can be one of the reasons why physicians have been focusing mainly on the large vessels, the epicardial vessels.

And the whole strategy to diagnose the disease and treat ischaemia has been focused on the large arteries, on the obstruction of the large arteries. So this inability of the tools to visualise microcirculation has actually delayed progress.

Nowadays we have some indirect ways of looking at the coronary microvessels and how they respond to different stimuli. For example we can carry out myocardial perfusion studies with cardiac MRI, and we are able to see abnormalities in the myocardium. So this is a test that is pretty accessible to physicians, and quite accurate at identifying abnormalities in the vasodialatory ability of the coronary microcirculation.

We can also use echocardiography to detect regional [or global] abnormalities in response to different stimuli. We can, if we take the patients to the catheter lab, carry out flow studies using a catheter to measure coronary blood flow in the catheter lab.

We are able now to increase blood flow using drugs like adenosine, for example. And we can measure the velocity and the amount of blood flow, or the increase in blood flow that results from the administration of these arteriolar vasodilators.

So we have quite a few tools.

Using acetylcholine during angiography is a very, very good way of looking at coronary microvascular spasm. We have carried out a study a couple of years ago in collaboration with Peter Ong and Udo Sechtem from Stuttgart, which has shown a large proportion of patients with chest pain and non-obstructive coronary artery disease having microvascular spasm, or diffuse distal epicardial spasm, being responsible for their symptoms.

So I would really encourage cardiologists around the world to use these accessible tools to diagnose the condition. Because identifying coronary artery spasm immediately gives you a target for treatment.

What does the future hold?
Discovering and understanding the mechanisms that lead to microvascular dysfunction and how microvascular dysfunction results in myocardial ischaemia in these patients is extremely important, and has opened new avenues for research in this area – particularly research into technologies that allow us to investigate the microcirculation more accurately, but also try to identify the right medication for these patients

At the moment we are using pharmacological agents that are useful in patients with angina and conventional obstructive coronary artery disease, but we know that the microvessel response to these drugs is not as good as it is with problems with the macro-circulation, in the epicardial arteries.

So I think progress in the future will be related to us identifying drugs which act specifically against the mechanisms responsible for microvascular angina.

Probably we will need to tailor the treatment, and we need to design drugs aimed at targeting specific pathways that result in this abnormal microvascular function.