• 22 Aug 2017
  • 15 min
  • 22 Aug 2017
  • 15 min

Dr David Liew interviews Dr Ingrid Hopper about the management of chronic heart failure. Diagnosing the type of heart failure is critical as it determines treatment. Read the full article in the August 2017 issue of Australian Prescriber.


Welcome to the Australian Prescriber Podcast. Independent, peer-reviewed and free.

I'm Dr David Liew, your host for this episode. It's a pleasure to be back and speaking to Dr Ingrid Hopper today about chronic heart failure. Dr Hoffer is the clinical pharmacologist and heart failure specialist at the Alfred Hospital in Melbourne. Dr Hopper welcome to the program.

Thank you very much. It’s great to be here.

So there seems like there's a lot of terminology that's changed in heart failure in recent years. Many clinicians were just getting used to the concept of diastolic heart failure and now in the last few years we've adopted newer terminology. Could you help clear this up in my mind and why is the distinction important between the different types of heart failure?

Sure. Well the commonest two groups, or the big two groups that we have in heart failure is heart failure with reduced ejection fraction and that's when the ejection fraction is less than 40%, or heart failure with preserved ejection fraction and that's where the ejection fraction is greater than 10%, and these are two very distinct groups and we need to have an echocardiogram because that determines what type of treatment pathway they go down. Whether they go down the ACE inhibitor, beta blocker, aldosterone antagonist pathway with HFrEF, or heart failure with reduced ejection fraction, or the other pathway with heart failure with preserved ejection fraction, which I'll talk about a bit later. In 2016 the European Society of Cardiology introduced a new heart failure category and that's called heart failure with mid-range ejection fraction. This is the ejection fraction of 40–49%. This was quite a controversial decision. The reason for this is because they want to stimulate research in that sort of grey area between the two obviously different types of heart failure but, as there's a lot of variation in measuring the left ventricular ejection fraction from test to test, it is quite difficult to determine exactly where that's going to go.

Right. So it does sound like it's a really important distinction in terms of trying to understand things. So maybe we can talk a little bit about, is it HFrEF first?

Yeah, so HFrEF, so heart failure with reduced ejection fraction, so that's the one where we have the most evidence-based therapy. So as you know heart failure occurs when the heart can't provide adequate cardiac output to meet the body's metabolic requirements and also accommodate venous return and it’s a clinical diagnosis and is based on symptoms. So the symptoms you're looking for are dyspnoea, orthopnoea and fatigue, and the signs you're looking for are pulmonary oedema and peripheral oedema classically.

This is a growing problem really, isn't it? What's behind this growth in HFrEF?

What we're seeing is a growth in heart failure generally. It's estimated that about one 1–2% of Australians have heart failure but really it's a disease of the elderly so it's present in about 10% of those aged over the age of 80 and increases with age. So heart failure is becoming more prevalent and there's a number of reasons for this. One is because the therapies are improved, which means that people are surviving their heart attacks. They're going on to have damage to the myocardium. It really is a testament to the great therapies that are around. Secondly the group of patients who have heart failure the medications are so good that they're living a longer time. Patients with heart failure with preserved ejection fraction – that's the group that's really increasing in size, so they're the patients who are elderly, they've got a lot of comorbid disease hypertension, atrial fibrillation, diabetes, obesity and they're getting stiff hearts. They describe that as like a tennis ball that's left out in the Sun over the summer and it becomes really stiff, and the problem is with heart failure formerly known as diastolic dysfunction, now called HFpEF, and that group is getting bigger and bigger. And about 50% of the patients that we see in an acute setting with heart failure have got heart failure with preserved ejection fraction.

That's a massive chunk of the of the pie and I guess that comes about actually cos people are living longer and like you say we're doing better at the things like ischemic heart disease.

And I think we've really seen a revolution in this disease over the last 30 years. It was before my time but back in the olden days beta blockers were contraindicated in patients with heart failure and then there was that entire you know 180-degree turnaround where they became indicated in heart failure.

And it's those treatments which mean that what we have now is light years away from what they had to deal with back in the day.

It must have been absolutely amazing. But to go from that they basically used to close the curtains and wait for these patients to die.

It really does sound like we're doing so much more for our heart failure patients. Now let's just go through some of the of the basic building blocks of the approach to heart failure so there are pharmacological and non-pharmacological considerations. Let’s start with some of the non-pharmacological considerations, given it’s such a complex management. How do we start to approach this? I mean there's a lot to cover.

Yeah well I think the most important thing to remember about non-pharmacological management is education and the GP is really central to this role – education on self-management. So first of all the patients should know the symptoms of heart failure and every patient's symptoms will be different. So some will have dyspnoea with usual activities or reduced exercise tolerance, others will have abdominal bloating or swelling of their ankles or a poor appetite, so they need to really hone in what their symptoms are of early decompensation and be educated and reminded of them. Secondly they need to have an action plan. They need to know the weight at which they're stable and what to do if their weight rises above a certain limit and and the Heart Foundation has a number of heart failure action plans available in different languages. I think they have 16 languages so print one up, give it to the patient, make sure that they do that every day and they know when to get in contact because early intervention is essential. And the third one with non-pharmacological measurement is really just the usual lifestyle factors so a low-salt diet, minimal alcohol, regular exercise and a cardiac rehabilitation program at some point after their acute diagnosis or an acute admission can be really beneficial.

So that's a really clear approach as to how to take that on. But once we've done all that, what are the building blocks in terms of the pharmacological approach to heart failure?

Well the foundation drugs are really ACE inhibitors and beta blockers, so all patients with heart failure with reduced ejection fraction should be on these drugs. ACE inhibitors have a really beneficial effect and they have a beneficial effect early and it continues long-term and it's in all age groups. Angiotensin receptor blockers haven't shown a consistent mortality benefit so they should only ever be used if an ACE inhibitor can't be tolerated and so that's for something like a cough that's persistent and irritating. The other thing that’s really important about ACE inhibitors is that you need to up-titrate them to target doses and this is where we see a lot of the problems with heart failure care. People start on the doses but they're not elevated to the level where we're going to get that mortality benefit, so we want to up-titrate every two to four weeks if we can, so long as the blood pressure is over 90 mmHg. If you get symptomatic hypotension then you should reduce your vasodilators or your furosemide first, so that you really put your efforts into up-titrating those ACE inhibitors.

What about the beta blockers because there's a whole series of beta blockers and we've always gone with the thinking previously that not all beta blockers are necessarily equal when it comes to heart failure management, is that still the case?

That is still the case, so it's pretty well all ACE inhibitors and ARBs are equal but it's not the case for the beta blockers. So there's only four that you should be choosing from and they're the heart failure specific beta blockers bisoprolol, carvedilol, metoprolol extended release or nebivolol if the patient’s over the age of 70.

So those are your building blocks really and it sounds like to get the best benefit really we're pushing the blood pressure there but if we've still got scope after that after reaching maximum doses what's the next step from there?

Well if the patients have still got symptoms then the next one we should be using is aldosterone antagonists. So these are insufficiently utilised across our society and it's really I think because people are a bit fearful of them. These include spironolactone and eplerenone if you've had an MI within the previous 14 days. One of the things really important when you're using aldosterone antagonists as with using ACE inhibitors is to keep an eye on the renal function and this is particularly so with the aldosterone antagonists because if you have underlying renal impairment or diabetes you can have a problem with hyperkalaemia, so the recommended monitoring regimen is you monitor them at baseline and then one week after starting, then one month after starting and then one monthly to three months, three monthly to twelve months, and then four-monthly after that. Often with patients with heart failure their renal function just deteriorates over time as they get older and so you just need to keep a watch on that every year.

Great, so on top of that, I mean now we're in the situation where if you've still got symptoms after having an ACE inhibitor, a beta blocker and an aldosterone antagonist we've got other options as well. So we've now recently got PBS access to a new agent, sacubitril with valsartan, for the treatment of heart failure. First thing first, what is sacubitril and how does it work?

Sacubitril is a neprilysin inhibitor and it inhibits the degradation of vasoactive peptides and these include natriuretic peptides. So this enhances the beneficial effects of natriuretic peptides which includes vasodilation and diuresis, also reduces sympathetic tone, reduces aldosterone and also reduces myocardial fibrosis. So this drug was put in a head-to-head trial against enalapril which was considered to be standard of care with other heart failure medications and it was found to have 20% reduction in relative risk of cardiovascular death and heart failure hospitalisation compared to enalapril. But that was only in patients who have got stable heart failure, so it wasn't used in the setting of acute heart failure. So this is a drug that will replace ACE inhibitors. If you continue to have symptoms when you're on an ACE inhibitor, beta blocker and aldosterone antagonists, continue to have symptoms of heart failure, switch the ACE inhibitor across to sacubitril with valsartan and then off you go.

And so now that it's combined with valsartan is there reason why they've chosen an angiotensin receptor blocker to combine with sacubitril rather than an ACE inhibitor?

The reason is because sacubitril has a risk of angioedema and the valsartan actually blocks the pathway that leads to the angioedema. But there is still a concern that people may get angioedema. It's more of a risk than an actual, there haven't been many cases of it, but when people are switching over from an ACE inhibitor to sacubitril with valsartan they need a washout period of 36 hours to make sure the ACE inhibitor is out and the way that this is often suggested is that patients take their last dose on the Friday morning of their ACE inhibitor and they switch on the Monday morning to sacubitril with valsartan.

So that's pretty scary. Have you had any problems in practice with angioedema? I mean you've had a bit of time now to play with sacubitril with valsartan.

Yeah I've had to play with this drug. I've had about ten patients who are on it and I haven't seen any, I haven't heard of any in Australia. It's more of a theoretical risk and that's why recommendations around a washout period are in place.

So all these drugs that we've talked about are ones that really are in the HFrEF algorithm. What about HFpEF? I mean how do clinicians start to make this diagnosis and how do we approach therapy in this area?

So HFpEF is the great challenge for heart failure for the next millennium. In the setting of acute heart failure you won't be able to tell which patients have HFrEF or HFpEF, but in the more chronic setting they're the type of patients who are usually elderly, typically female with comorbidities, and they really present with exertional dyspnoea. So they’re fine when they're sitting still, take off for a walk and they really struggle with their breathing. So that's the typical presentation. You always need to have an echocardiogram in order to make the diagnosis and that will show the heart failing with the preserved ejection fraction and some difficulty with diastolic relaxation. And so that's the physiological problem is difficulty in filling, in the setting of increased metabolic demand.

Great so in terms of the therapeutic approach to this, what drug are we meant to use because I've heard a lot of things about whether maybe ACE inhibitors have some potential or beta blockers have some potential but I've never really been sure what to do for this patient.

Yeah and it is really tricky. A lot of drugs have been investigated but none have shown a mortality benefit. Some have shown an increase in exercise capacity or quality of life. The one that's being investigated now is sacubitril with valsartan. There was a phase 2 trial which showed some positive results and that's currently under phase 3 investigation so we'll wait and see what happens there. But otherwise it really is around maximising the other comorbidities so hypertension is a particularly important one so it's important to get the blood pressure well under control. You should really avoid over-diuresis and regular exercise is really really important for these patients to really push themselves.

So it sounds like it's a real challenge really and it's not necessarily easy to integrate the complex mechanisms that underlie a lot of that are working in HFpEF. How can you bring it all together in practice? There's a lot of non-pharmacological things to bring into place, not necessarily directly related to heart failure, there's the management of medications with some specific things required. How can you bring it together in real life?

In real life I think the important thing is the GPs, and the GP and the patient are central to their care. So when the patient comes out after admission for acute heart failure or a new diagnosis of heart failure that's when the GP really needs to kick in and the GP is crucial in the management of the transition back to the community. So the first thing might I would suggest is that the GP reviews the patient within seven days of discharge and this intervention has been really shown to reduce re-admission rates, to get in early, check on their education, reinforce the heart failure action plan, and use the opportunity to up-titrate the heart failure medications if you can. Again get that therapeutic relationship going, hear from the patient when they’re deteriorating early, and then involve the carer of the heart failure specialist to make sure that the medications are maximised and hopefully we'll be able to really improve the quality of these patients’ lives by keeping them in the community rather than in and out of hospital.

Great. Well that's all we've got time for. Thanks very much for joining us Dr Hopper.

It’s a pleasure. Thanks very much for having me David.


The full article is available online at nps.org.au/australian-prescriber and like our whole journal it's free. Subscribe to get the latest Australian Prescriber delivered straight to your email inbox and follow us on Twitter @AustPrescriber to get the latest updates. The views of the host and the guest in this podcast are their own and may not necessarily represent Australian Prescriber or NPS MedicineWise. I'm David Liew and thank you for joining us on the Australian Prescriber Podcast.