Cardio-oncology: Dr Rebecca Dobson on how to harmonise heart and cancer care

Speaking at Hospital Healthcare Europe’s Clinical Excellence in Cardiovascular Care event, Dr Rebecca Dobson discussed the acute need to assess cardiovascular risk in cancer care, understanding cardiotoxicity and the importance of multidisciplinary team coordination in cardio-oncology.

Following on from her previous Clinical Excellence session in which she discussed the need and demand for cardio-oncology services, Dr Rebecca Dobson, consultant cardiologist specialising in imaging and cardio-oncology at Liverpool Heart and Chest Hospital, turned her attention to considerations such as baseline assessment, cardiovascular risk factors and the impact of systemic anti-cancer therapy on the cardiovascular system – even years down the line.

Dr Dobson also championed collaborative care between cardiology, oncology, radiology and other fields to ensure patients can continue their cancer therapy alongside cardio-protective therapies to optimise their short- and long-term outcomes.

Why is it so important to assess cardiovascular risk?

Trends change, and cancer is becoming more common, but happily cancer survival has also doubled in the UK in the last 40-50 years. It’s really important that we, as cardiologists and cardiology teams, don’t shy away from this group of patients, because there’s a lot we can do from a cardiovascular perspective to help them live long, healthy lives after they’ve had cancer.

The authors of a recent paper in the European Heart Journal looked at all patients with cancer and stratified them according to cancer mortality rate and cardiovascular disease mortality rate.

In one group, the patients sadly have very high cancer mortality rates (70-90%) and, as a cardiologist, there’s very little I can do with that cohort of patients to change the natural trajectory of that disease. The impact from a cardio-oncologist perspective is relatively low.

The second group of patients have a slightly lower cancer mortality rate (40-60%) and an increasing cardiovascular disease mortality rate (10-20%), and there’s more we can do in terms of trying to reduce long-term effects of systemic anti-cancer therapies and reducing the risk of cardiotoxicity to avoid cardiovascular complications.

In the third group, these patients are as likely to die from cardiovascular disease as they are from their cancer – both at 20-30%. It’s really important that we don’t cure these patients’ cancer and then leave them alone. We really need to optimise the cardiac care of these patients to consider them as a whole, not just as a cancer patient.

At what point in a patients’ cancer journey are they seen within the cardio-oncology service?

As a consequence of increasing cancer rates and survival, more patients are being exposed to potentially cardiotoxic therapies, and more people with pre-existing cardiovascular disease – who 30 years ago would have died of their cancer – are now surviving. That’s where the subspecialty of cardio-oncology has come from.

We specifically see three different groups of patients. Firstly, we see patients at the beginning of their cancer journey to risk-stratify them. That could be a patient with any cardiovascular disease who then receives a cancer diagnosis and needs to be risk-stratified and optimised from a cardiovascular perspective. Importantly, there needs to be a discussion with the oncology team about that patient’s cancer therapy to ensure it won’t destabilise their existing cardiovascular disease.

As patients go through their cancer journey, we screen and monitor them to detect cardiovascular injury at earliest possible stage so we can get them on appropriate cardio-protective therapies and reduce the interruptions to systemic anti-cancer therapy.

This has been a big change over the last 10 or 20 years. Historically, if you had cancer and then you developed potential cardiotoxicity, it was a binary decision. Sadly, for these patients, cancer therapies were generally discontinued, whereas now we try to continue cancer therapy wherever possible.

The last group of patients we see within the cardio-oncology service is screening and monitoring patients who are cured of their cancer but are at risk of significant long-term cardiovascular late effects.

Classically, this would be patients who had a haematological malignancy or a bone cancer as children or young adults and received significant amounts of anthracycline chemotherapy. We know that puts them at risk of late-effects even 30 years later.

We don’t want these patients to be discharged and forgotten about but then present in adulthood in heart failure. So, we’ve set up a service, certainly in Liverpool, whereby every patient who has had a significant dose of anthracyclines gets put into a late effects clinic. We see them every three to five years, so they don’t fall off that cliff.

How do you encourage oncologists to focus on that baseline assessment as well as more immediate cancer treatment?

Baseline assessment is a little bit contentious from an oncology point of view, and oncology teams have a lot to do with their patients when they first get their cancer diagnosis. To then ask them to also risk-stratify patients from cardiovascular perspective is challenging.

As a cardio-oncologist, I see my role as facilitating this baseline assessment and I work with the region’s oncology teams to do this.

It helps us consider what changes may be required to systemic anti-cancer therapy and enables us to potentially detect undiagnosed cardiovascular problems at baseline.

We are performing increasingly more investigations on patients receiving chemotherapy and radiotherapy. It can be difficult to interpret these investigations without a baseline for comparison otherwise we won’t know if cancer therapy has caused an issue or whether there was pre-existing disease. It also enables us to reduce the risk of cardiotoxicity as patients move through treatment.

I recommend that you download the European Society of Cardiology’s guidelines on cardio-oncology because it gives a helpful overview. It’s a large document but there’s lots of useful information in there.

What are the red flags, and what tests are required?

When I talk to oncologists, they’ll often ask, ‘how do we assess cardiovascular risk, what is it we need to do?’ The first thing to say is that not every patient needs every test. I’m a real believer in that there’s no point doing a test unless you know what you’ll do with an abnormal result. That’s particularly challenging for oncology teams who aren’t used to dealing with echoes, troponins, NT-proBNPs, cardiac MRI scans or sometimes even ECGs.

It’s really important to tailor the approach to the patient depending on their comorbidities and what systemic anti-cancer therapy is proposed. Things like age, sex, demographics, past medical history, lifestyle factors like smoking or being overweight, a family history – if alarm bells are ringing as the history is being taken and the examination is happening, then you might think that the patient needs to go on to have further complementary tests.

It’s really important when we’re setting up these services that cardiology teams work collaboratively with oncology teams to make sure pathways are in place to help us work out what we’re going to do with the abnormalities.

How is risk objectively quantified, and what conversations do you have with patients about their risk?

There’s an easy way of quantifying risk now. If you download the free ESC app, you can access risk calculators. It’s easy to fill out the yes or no questions and it gives you a risk at the end: low, medium, high and very high.

The four outcomes are very arbitrary, but the ESC cardio-oncology guidelines stipulate that this is the approximate risk we should be discussing with patients – high-risk conversations will be very different to low-risk ones.

If you’re low risk, you’ve got a less than 2% chance of developing cardiotoxicity, although note that it’s not zero – I always tell patients we can never say they won’t develop a cardiovascular problem. Low-risk patients should have standard monitoring, and, hopefully, as cardiologists or cardio-oncologists, we don’t need to get involved with them.

Medium-risk patients should have closer monitoring, which will differ depending on your region’s resources. We don’t see medium-risk patients here, but we often speak with oncology teams and suggest closer echo or blood pressure monitoring, whatever the issue might be.

High-risk and very high-risk patients have a substantially increased risk of cardiotoxicity. A cardio-oncologist or a cardiologist with an interest in oncology should be involved to optimise them from a cardiovascular perspective. It’s about having an open discussion with the oncologist about their proposal and the additional risk and then feeding that back to the patient.

I tell patients this is a balancing act and we’re trying to ensure the benefit of cancer treatment outweighs cardiovascular risk. There are only few circumstances where it doesn’t and the risk of killing them with chemotherapy is higher than the risk of curing them.

People have different levels of acceptable risk and different priorities, so involving them in decisions is really important. My role is to facilitate safe cancer therapy.

Tell us about the breadth of systemic anti-cancer therapy cardiotoxicity

Whenever we thought about cancer and the heart, we used to think about Herceptin and heart failure. Certainly, we do see left ventricular systolic dysfunction associated with Herceptin, but nowhere near as frequently as we used to because of all the cardio-oncology measures that are in place.

Occasionally we see patients with dramatic cardiotoxicity that develops as they’re receiving their cancer therapy. Classically, for example, someone who is receiving paclitaxel and acutely decompensates. They might get chest pain or go into heart failure, but, actually, these patients tend to do well and it’s reversible so they recover as quickly as they deteriorated.

We see patients who have early cardiotoxicity in the days and weeks following systemic anti-cancer therapy, or we can see it months or years later. There’s a challenge there to unpick the timeline and work out what’s causing what. Certain drugs are good at causing late effects and other drugs cause acute cardiotoxicity.

I learn all the time, as cancer therapies develop, about new cardiovascular toxicities or new presentations of cardiotoxicity. It’s really important to keep an open mind when looking after patients who have cardiac issues and have received, or are receiving, systemic anti-cancer therapies and think could these two things be related.

Not only do we see a spectrum in terms of the timeline, we see a spectrum with the cardiotoxicity and the clinical presentation.

What are some of the key risk factors that should be identified and managed?

Hypertension is hugely under-recognised and under-treated in cancer patients. We know there’s a lot of overlap between risk factors for cancer and for cardiovascular disease, so it’s not surprising that many cancer patients have hypertension. If you add in that they’ve been diagnosed with cancer; they’re likely to be undergoing challenging, difficult-to-tolerate treatments; and they’re anxious, frightened, in pain, anaemic and tired – all these will raise their blood pressure.

Then you’re giving them cancer drugs, many of which can cause hypertension. We can see why 40% of patients with cancer have hypertension. But we undertreat it and we excuse it, but we should be managing it like we would with any other patient with hypertension. We should be monitoring them appropriately and getting them on antihypertensive medications.

Vascular toxicity tends to be more of an issue with the treatments we use for gastrointestinal cancers. We see destabilisation of coronary artery plaques, patients presenting with myocardial infarction, patients with coronary artery spasm. This may just be a bit of indigestion-type chest pain, and the patient may not even present to a healthcare professional but, at the other end of that spectrum, we’ve seen patients with coronary artery spasm who’ve presented with a cardiac arrest. It’s really important that these patients are taken seriously when they say they’ve got chest pain and that everyone is aware that it is a recognised vascular toxicity of the these chemotherapeutic agents.

How are newer cancer treatments affecting the heart?

Myocarditis is an increasing worry with patients who receive checkpoint inhibitors or immunotherapy. When I started in cardio-oncology, we only used immunotherapy for patients with melanoma or renal cell carcinoma. Now, around 75% of cancer patients are eligible for treatment with immunotherapy and that’s not just in a palliative setting, but in a neoadjuvant and adjuvant setting.

Checkpoint inhibitors have a 2% risk of causing myocarditis, and if we miss this and don’t treat it, the patient will die from the myocarditis. So, it’s really important that we consider this in patients who have received immunotherapy because they may present innocuously with fatigue, ankle swelling, breathlessness. You can see there’s a challenge there because what cancer patient doesn’t have those symptoms? But keep it in mind for these patients because the sooner you recognise it, the better the outcome for the patient.

But it’s not all about cardiac function. We need to consider blood pressure, QT interval, myocarditis and, thinking about later effects, things like ischemic heart disease.

Patients who had radiotherapy, particularly mediastinal or left-sided radiotherapy, many years ago can present years down the line with quite significant proximal coronary artery stenoses. And it never fails to amaze me how many patients forget to tell you they’ve had cancer when you’re taking their history. I think a lot of patients block it from their memory. So, particularly if a younger patient is presenting with angina-type symptoms and you think it’s a bit unusual, always ask about their cancer history specifically.

How do you detect cardiotoxicity?

I always say to the oncology teams regionally that cardiotoxicity is a bit of a jigsaw. Certainly, understanding the patient’s clinical presentation is key, and then using that with complementary biochemical and other cardiac investigations to fit everything together.

Within cardiology teams, we’re all familiar with troponin and NTproBNP, but remember, the oncology teams are not. It’s important we help them interpret these and have pathways in place so they know what to do with abnormalities.

Imaging, obviously, is our backbone of decision making within cardio-oncology. It’s really a complimentary modality to help us put into context the clinical signs and symptoms and the biochemistry. Where possible, we should be measuring global longitudinal strain (GLS) and ejection fraction using 3D volumes in all our oncology patients.

We know 3D volumes are more reproducible and have less temporal variability. We don’t want to stop someone’s chemotherapy because we think they’ve dropped the ejection fraction when, actually, it’s just because the pictures were a bit rubbish and the 2D ejection fraction was way off. We need to make sure we’ve got accurate, reproducible echo data to help guide our decision-making.

How does permissive cardiotoxicity fit into this?

There’s been a real shift over the last decade in trying to continue chemotherapies and radiotherapies and permitting a certain degree of cardiotoxicity. It comes back to the question of at what point does the risk outweigh the benefit?

It’s about changing your mindset from ‘should this therapy be discontinued’ to ‘how can this therapy be continued’. Because we know that if we interrupt anti-cancer therapy, it’s an independent prognostic marker for worse disease-free survival and overall survival.

For the patients with asymptomatic cardiotoxicity or mild-to-moderate cardiotoxicity, the challenge is trying to work out what to do to safely continue their cancer therapies. And that’s where the cardio-oncology service comes in with increased screening, monitoring, optimising of cardio-protective therapies.

It’s important that if we stop therapies, we consider rechallenging them. In the past, nobody would be rechallenged, but many patients will have a successful rechallenge once they’ve been optimised from a cardiovascular perspective.

That brings us back to the multidisciplinary team (MDT) and the importance of that two-way discussion with cardiology and oncology in terms of making sure that we’ve thought about everything to enable treatment to continue or be restarted.

How does that collaboration work at your centre in Liverpool?

When you’ve got a cardiologist making unilateral decisions, you’re going to run into difficulties. A pivotal part of our service is that we see patients quickly. There’s no point a patient being referred with their chemotherapy discontinued and me saying I’ll see them in six months, which is probably what a lot of cardiology outpatient waiting times are. We’ve set our service up to see patients within two weeks. If we can’t see them within that timeframe then we offer advice on cardiovascular risk to ensure treatment interruptions are minimised.

Efficient communication throughout is important. I work at Liverpool Heart and Chest Hospital, four miles from Clatterbridge Cancer Centre. That’s a different Trust with a different electronic patient record. We can’t see each other’s echocardiograms, so it’s challenging, but we’ve worked hard to improve communications between the teams.

We’re becoming more aware that it’s not just thinking about a patient’s heart or cancer but thinking holistically because these patients are complex and we want to get the decisions right.

In terms of the MDT, people dip in and out, depending on the patient and the clinical need. We have cardiologists, a cardio-oncology specialist nurse, specialised cardiac physiologists, medical and clinical oncologists, palliative care specialist nurses, pharmacists, radiologists, surgeons, anaesthetists, a dietitian.

When I started the cardio-oncology service in 2019, we ran a fortnightly clinic, but now we run three per week. We have a weekly ward round at Clatterbridge Hospital, four weekly oncology echo lists and a weekly virtual MDT where we ensure we have oncology, cardiology and radiology representation as a minimum.

Everyone’s perspective is different, and it’s really important that we all understand these to ensure that patients have the right decisions made.

To what extent do you see cardio-oncology being embraced around the UK?

Momentum is increasing, and certainly people are more aware of it now than they were 10 years ago. There are not many fully fledged cardio-oncology services, but I think more and more cardiologists and oncologists are aware of cardiotoxicity and are seeing patients within their clinics and realising they need to funnel them in a slightly different way.

We’re all aware that the NHS has no money, so trying to develop business cases and set up new services is incredibly challenging, but one of the things that I feel really strongly about is if we set up those services and risk stratify patients to optimise them at baseline, we’re hugely reducing the risk of cardiotoxicity and saving money. The drugs that we use to treat cardiotoxicity cost tens of thousands of pounds per patient, and if we can reduce the risk of that happening in the first place, prevention is definitely better than cure. I think the service will pay for itself over time, but that is very challenging.

What are the challenges and what tips do you have for setting up a responsive cardio-oncology clinic?

The challenge is getting enough people interested. Everyone is busy and when you go along to a TAVI operator or a cardiothoracic surgeon and say, ‘I want to get you interested in cardio-oncology’, people run the other way. But the service does speak for itself: the more patients we see, the more we assess cardiovascular risk, the less interruptions to systemic anti-cancer therapy are happening. The oncology team certainly values the service, and they are desperate for help with this group of patients.

So, in terms of tips for setting it up, get an interested oncologist on board and start your discussions there to build a joint business case.

How do you manage challenges with funding and capacity in clinics?

In terms of funding, it took me four years to get funding for a cardio-oncology specialist nurse. The only way I managed in the end was getting our local Cancer Alliance to fund a year’s salary and a private donor contributing as well. We’re all facing challenges in the current climate and it’s about looking at alternative funding sources. So, could your local hospital charity do a funding campaign for you to help with these services?

With capacity, the way we’ve set the service up means these patients are all going through dedicated cardio-oncology clinics. We make sure we save urgent slots every week, but we drowned in patients after a couple of years and I suspect that as demand goes up again, we’ll struggle. But for now, we’ve just doubled the number of clinics that we offer, and having a cardio-oncology nurse specialist has further allowed us to increase our capacity.