Giuseppe Rosano, visiting Professor at Medical School, St George’s Hospital, University of London, UK, talks to Cardio Debate about oestrogens, microvascular angina & possible treatments, and new therapeutic treatments in heart failure.

TRANSCRIPT

Oestrogen and coronary artery disease (CAD) and microvascular angina in women: is it a pathogenic mechanism? Why? Is there a treatment?

Oestrogens are very important to women, and are important throughout their life. What is important is the balance between the oestrogen and progestin.

After menopause, there is a drop in oestrogen levels. And oestrogen is a naturally occurring calcium antagonist. So basically, after the menopause there is a loss of the vasodilatory effect of oestrogens, and this causes an increase in blood pressure on one side, on the other side an increase in vascular resistance.

On the other hand, oestrogens have at least 300 different actions at the genome level that influence activities like the renin-angiotensin-aldosterone system, the release of naturetic peptides, the release of vasoconstricting factors, and therefore all the changes that occur after the menopause, altogether coexisting, cause an increase in vasomotor tone.

Now this increase in vasomotor tone is increasing vasoconstriction, causing an increase risk – or increased prevalence – of microvascular angina. And part of the changes that are occurring with the oestrogens are evidenced in some women before the menopause. For example, women with catamenial migraines, so migraines that occur before the menstrual cycle. These are women that are more prone to develop these vasomotor changes with the drop of oestrogens.

Regarding the mechanisms, it’s not just related to one single factor, there are several factors that are related to oestrogens.

Regarding the treatments, we were shown a long time ago that oestrogen replacement therapy is effective in improving symptoms and exercise capacity in women with microvascular angina.

What is important with hormone replacement therapy, is that it is started early after the menopause. Because if it is started too late it may be helpful, but if it is started early after the menopause it confers some benefit.

And in those women with microvascular angina, it may give them significant symptomatic benefit.

Which are the current effective treatments for Heart Failure? What are the new drugs with different mechanisms of action for heart failure?

Regarding heart failure, we have two different faces of the coin. On one side we have acute heart failure where we don’t have any new treatment that has been shown to be effective for the past 15 years. And so we are still looking for effective treatments that may be effective in the acute phase.

But patients that survive the acute phase, patients that become chronic, then in these patients we have several drugs that have been proven effective in the past 20 years, like ACE-inhibitors, Beta-blockers and mineralocorticoid receptor antagonists

Now, these three class of drugs are extremely effective at reducing mortality and morbidity. After these three drugs are implemented, in patients with sinus rhythm ivabradine is a drug that is effective at reducing the composite end point of mortality and morbidity. So it is a drug that should be considered in all patients who are still symptomatic despite treatment.

There’s a new treatment that has been shown to be effective, and it is the combination of valsartan and sacubirtil. This is a new molecule. Basically they took two molecules and bonded them together into one chemical entity. So in theory they are two different drugs that have been put into one single molecule.

This combination has been shown to be effective in reducing mortality and morbidity in patients with chronic heart failure with increased levels of naturetic peptides, or who were still symptomatic after maximal therapy with background therapy. The effect of valsartan/sacubitril, or LCZ696 was more significant at that which was achieved with a sub-optimal dose of enalapril – an ACE-inhibitor.

So it is a very promising drug. What is important for valsartan/sacubitril is to understand in which patients it can be used safely, because of course the sign of the study identified a very specific patient population – which patients can tolerate the drug that may induce hypertension. But once these two main problems are solved, it will be a very important drug that will further improve the benefits that we already have in heart failure.

Now together with drugs, we have devices. And we are learning that resynchronization therapy is extremely effective, implantable cardioverter devices are extremely effective. Now the new trials testing the effect of mitraclip that basically repairs the dysfunctional mitral valve should give us results soon, and if proven positive then could be suggested for clinical indication.