Assessing and Managing Stroke Risk in Adult Congenital Heart Disease

Melissa Lyle, MD; Naser Ammash, MD; Christopher McLeod, MB, ChB, PhD


March 27, 2017

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Melissa Lyle, MD: Hello everyone. I'm Dr Melissa Lyle, cardiology fellow at Mayo Clinic. Today, we will be discussing how to assess stroke risk in patients with adult congenital heart disease [ACHD]. I'm joined by my colleagues, Dr Naser Ammash, professor of medicine, and Dr Christopher McLeod, associate professor of medicine, who both specialize in this area. Thank you both so much for joining us.

Naser Ammash, MD: Thank you for having us.

Dr Lyle: I am aware that patients with adult congenital heart disease are at increased risk for stroke, but could you describe the overall incidence in this population?

Risk Factors for Stroke in ACHD

Dr Ammash: Compared with the general population, adults with congenital heart disease have a significantly increased risk of stroke. In women, it's around 6% to 8% in their lifespan until age 65, and in men, it's 8% to 9% in a study done in Canada, including 30,000 patients followed over a long period of time.[1] So it's a 10-fold increased risk compared with patients the same age without congenital heart disease.

Christopher McLeod, MB, ChB, PhD: For each specific syndrome, it's obviously different. Some of them are going to be 100 times more likely than the general population, some of them a few times.

Dr Ammash: Many variables play roles in determining which [syndrome] is the most predisposed, which is the least predisposed. The patient population is so diverse.

Dr Lyle:In that regard, what are the most common mechanisms for stroke in this population?

Dr Ammash: Atrial fibrillation and flutter are very common as patients get older, especially if they have had multiple operations before. I would say that's the number-one major risk factor.

Dr McLeod: And heart failure. In heart failure, we don't know how much of that atrial arrhythmia is subclinical and how much is a manifestation of the heart failure—the left-sided heart disease lesions and patients with ischemic heart disease. We're getting into the older population, which has some of the usual risk factors, heart failure being the first one for their CHA2DS2-VASc score and also age. It's an age-dependent increase.

Dr Ammash: Unfortunately, in our patient populations with congenital heart disease, the chances of them having heart failure increases significantly as they get older. The risk of atrial arrhythmia significantly increases as they get older, and these are two major risk factors for stroke in everybody.

For example, some patients with clotting problems are at a higher risk for strokes. Or some patients have holes in their hearts, so they're at risk of what we call "paradoxical embolism."

That's why every patient is different, and we have to assess the risk in each patient and determine what we can do to reduce the risk and prevent strokes. This is the most feared complication. It has a significant impact on patients and their families and everybody around them, so that's very concerning.

Dr McLeod: Stroke risk is higher in patients with Eisenmenger syndrome where the blood viscosity is different, the hemoglobin is higher, but clotting is abnormal. ACHD patients undergo many more interventions. Any time we start sticking catheters in patients—we try to close holes and put plugs in and devices—then that increases risk for stroke.

Risk-Stratification Tools in ACHD

Dr Lyle:As a fellow, if I'm seeing a patient with adult congenital heart disease in my clinic, what tools are available to me for risk stratification?

Dr Ammash: Every patient is different. It really depends on underlying anatomy, the rhythm, and the associated acquired problem with [each] patient, keeping in mind that more than one-third of our patients are older than 45 years.

So the tools available for us are what we know about the risk of strokes in that specific patient—also keeping in mind what [interventions] a patient has had before [such as] surgery. This is when we assess the risk and ask whether we need to do anything about it, such as start anticoagulation, or whether we can reduce the risk of stroke without starting anticoagulation. It's case-to-case, and we discuss it all the time.

Dr McLeod: It's a difficult [issue], definitely at a center that sees a lot of ACHD. If you have a patient with pulmonary hypertension and you're worried about a catastrophic bleed in the lungs from pulmonary hemorrhage, we don't have a good risk-stratifying tool to know whether to start that person on a blood thinner for diabetes, heart failure, or some other comorbidity that would predispose them to atrial arrhythmias, because it's a different kind of risk of bleeding.

Dr Ammash: The tools we have are for acquired heart disease; we don't have ones specific to congenital heart disease—our estimates are based on experience. Ironically, the same patients who are predisposed to strokes and blood clotting can also be predisposed to bleeding, so you have to really assess the risk in Eisenmenger, Fontan, and patients with liver disease. Keep in mind that these are predominantly young adults. If you commit them to anticoagulation, that's a big deal for them. No matter what medication we give them, it's different from [that for] somebody older because of the longer life-span for them.

Anticoagulation Management in ACHD

Dr Lyle:Once you decide to anticoagulate the patient, what's the general approach for management of anticoagulation?

Dr Ammash: For years, we have been dependent on warfarin. Especially in complex patients, we feel more comfortable with it. But the patients read the news, they watch TV. They know about the direct anticoagulants available now, especially because they don't require blood tests for the international normalized ratio (INR).

But the vast majority of our patients have been on warfarin [long term] if we believe they are at an increased risk of stroke without significant increased risk of bleeding. We have thousands of patients who have prosthetic valves and irregular heartbeats that have been on warfarin. But consideration of the newer anticoagulants, the direct ones, is valid. What do you think, Chris?

Dr McLeod: We obviously don't have much data. There are a couple of small cohort studies that show it's safe, but follow-up is not long.[2] That being said, even though we've been using warfarin for all these years, we don't have any good data on warfarin either.

Dr Ammash: I don't think there's been a randomized clinical trial on warfarin in adult congenital heart disease, but we know it works and it reduces the risk of stroke by 70% in newfound congenital patients. We feel comfortable with it, and the patients have been on it before.

But why not [consider] other drugs as we become more comfortable using them, especially as compared with adults with acquired heart disease? When you look at causes of stroke in congenital [heart disease], it's predominantly ischemic stroke, not bleeding. Around 80% of all strokes are caused by ischemia and 20% by intracranial bleeding and subarachnoid hemorrhages. In adult congenital heart disease patients, 99% of stroke is related to ischemia, unless the patients have an intrinsic problem in the brain that predisposes them to bleeding. That is a factor we have to consider, but we have many patients treated with direct oral anticoagulants.

Dr McLeod: In some ways, we're extrapolating from these bigger atrial-fibrillation trials,[3,4,5] the apixaban [Eliquis, Pfizer/Bristol-Myers Squibb] large trial[4] comparing warfarin with apixaban in patients with atrial fibrillation without congenital heart disease, without significant mitral stenosis, and the edoxaban [Savaysa, Daiichi-Sankyo] trials; some of these patients have bioprosthetic valves. Some patients had native valve disease, so we're excluding mitral stenosis. There was no signal that these new drugs were more dangerous, and there was definitely a trend toward less bleeding, which is the real advantage.

Over time, as we become more comfortable with them—as we get a reversal agent for the factor Xa inhibitors, and we have a reversal agent now for Pradaxa [dabigatran etexilate, Boehringer Ingelheim]—then I think it's probably going to evolve. There are ongoing trials using the direct anticoagulants in adults with congenital heart disease who have atrial arrhythmias.

Dr Ammash: One of the challenges of those trials is the diversity of the patients we see. If somebody has simple congenital heart disease, such as an atrial septal defect [ASD] and they have an atrial arrhythmia and we do an ablation, then I'd be very content to use newer anticoagulation.

However, if you have a patient has a right atrial fenestrated Fontan connection TCPA ( Total cavopulmonary anastomosis) and atrial arrhythmia, I'm not sure I would feel comfortable using direct anticoagulation, although it might be okay. What do you think?

Dr McLeod: We just don't know. There definitely isn't the same level of comfort. We're starting a new era, and certainly there isn't any evidence so far that these newer agents are going to be particularly riskier. Are they going to be as effective? We're not sure.

One lesson borne out by all of the other registry or large systematic reviews[5,6] of patients with valvular heart disease is that they're at higher risk. There is a lower threshold to start an anticoagulant in someone with congenital heart disease because they almost certainly have a higher risk. But it is syndrome-specific. You can have severe right-sided heart disease, severe right ventricular dilatation, and the left atrium is normal, the left atrial appendage is normal, the left-sided heart function is normal. So, for that patient, maybe [anticoagulation] is unnecessary. It really needs to be individualized. If you look at anyone with a left-sided lesion who has valvular heart disease, they're at higher risk of stroke.

Dr Ammash: What I suggest is shared decision making with those patients. I usually tell them what we know, what we don't know, and the treatment options. If we decide direct anticoagulation, then we say, "We use it in adult patients with acquired heart disease, and it has worked. This is the risk of bleeding vs warfarin, which we have used before."

The challenge is if somebody has been on warfarin for a long time in the therapeutic range with no complications, then why would you rock the boat? In newer patients, we have that same discussion of what we know and what we don't and then make a joint decision (as long as the renal function is normal), but that's very important for the direct anticoagulants.

Dr McLeod: The other [point] to make the fellows aware of is that, for the younger patients on warfarin, there are good data[7,8,9] suggesting that there's going to be less bleeding and less thromboembolic stroke if the [patients] check the INR themselves. The home INR checking is crucial for the patient. They're going to become better at doing it than their clinic, which has changes in staff and approach. They know when they're traveling, when their diet has changed.

Dr Ammash: We suggest home INR monitoring in everybody. They patients are dependable about it, typically, because they have had heart disease for a long time.

ACHD Guidelines and Takeaways

Dr Lyle:Thank you, that's very helpful information to know. What are the most important and current adult congenital heart disease guidelines that we should be aware of while caring for these patients?

Dr Ammash: We have the [American College of Cardiology/American Heart Association] ACC/AHA guidelines from 2008,[10] but the new guidelines are due out shortly. Those [will address] disease-specific evaluation and treatment and provide suggestions on how to monitor these patients, but it's going to be disease-specific. There will be some sections on stroke, but typically we talk about stroke in each disease because it varies from one disease entity to another.

There are other guidelines, [Grown-Up Congenital Heart] GUCH guidelines from the Europeans and the Canadian guidelines—three major guidelines address the treatment of adults with congenital heart disease. The one from 2008 is the major one; Dr Carole Warnes was the first author on it from Mayo, but the newest guidelines are coming very soon.

Dr McLeod: From an arrhythmia point of view, there is the 2014 consensus statement[11] on the management of all arrhythmias in adults with congenital heart disease. That includes a specific algorithm for how to treat the adult with congenital heart disease who has an atrial arrhythmia with regard to anticoagulation. The authors fully disclosed that this is level of evidence C, so this is expert opinion only. There are no data for this. They break up the approach into "complex" vs "simple" congenital heart disease. For complex congenital heart disease—it is quite a complex group of disorders—you're almost always going to go with warfarin.

Dr Ammash: It's safer.

Dr McLeod: For simple congenital heart disease, if there is any valvular heart disease lesion, then [the authors suggest] anticoagulants. And they are guessing, but they are saying direct oral anticoagulants or warfarin. But if the patients don't have any significant valvular heart disease, and it's simple congenital heart disease, then you can probably use a CHA2DS2-VASc score. So this would be the 69-year-old with repaired ASD now with some atrial fibrillation. How do you treat them? If they are 69 and they've got diabetes and hypertension, then you probably should use a CHA2DS2-VASc risk score. If they're 41 years old, you can probably go down that route.

Dr Ammash: In most younger patients, the CHA2DS2-VASc score will be low because they don't have the disease entity. One important [consideration] is cardioversion in these patients. We have a protocol in which practically everybody who has congenital heart disease gets [transesophageal echocardiography] TEE before cardioversion and we anticoagulate. In that case, I think it's okay to use a direct anticoagulant before and after cardioversion. I feel it's safe, especially if it's a patient with simple to moderate congenital heart disease.

In the complex patient, [however], we err on the side of what we know, what has worked before, and use warfarin. But in that group of patients we have to pay particular attention because with structural heart disease, they are more predisposed to thrombus formation and strokes related to cardioversion.

Dr McLeod: The other [point] that is recognized though not well reported is if a fellow or cardiologist comes across a patient with one of the classical Fontan procedures (this right atrium [RA]-to-pulmonary artery [PA] Fontan that can be these very big, baggy chambers), despite anticoagulation you can still have thrombus. You should do a TEE for an elective cardioversion; even if the patient has been anticoagulated and their INR has been between 2 and 3, they can still develop thrombus, and [cardioversion could] dislodge those. You can have a fatal pulmonary embolus (PE) in that situation.

Dr Ammash: Up to 20% of these patients have silent PE without us doing anything, so I think that's very important, especially RA-PA connections.

Dr Lyle:Thank you so much, Dr Ammash and Dr McLeod for joining us today and for your insight into this very important topic. Thank you all for joining us on on Medscape.


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