Research Roundup–Second Installment…

Welcome back to the second installment of Research Round-Up, and thanks to those of you who read, shared, and commented on our first column: https://scadalliance.org/latest-news/research-round-up-1/

For Heart Month, we thought it would make sense to summarize one of the most recent reviews of SCAD research. In 2020, Dr. Esther Kim,* a noted expert on SCAD and chair of the SCAD Alliance Scientific Advisory Board, published a great review article on SCAD, which incorporated all the recent research. It’s a meaty, incredibly valuable article, deemed worthy enough for publication by perhaps the most esteemed medical journal there is: The New England Journal of Medicine. I hope I can do it justice here, and that this summary is valuable to those of you who are interested in the basic scientific landscape of SCAD to date.

WHAT IS A SCAD?
Dr. Kim defines SCAD as a separation and hemorrhage within the layers of a coronary artery wall, which may or not involve a tear in the artery wall. SCAD is not associated with atherosclerosis like most “typical” heart attacks. Later, she explains the different types of SCAD as defined in a new-ish classification system. More later…

In 90% of patients, SCAD is evaluated as a myocardial infarction. 20-50% of those patients have an ST Elevation Myocardial Infarction (STEMI). The rest are patients with non-STEMI heart attack. 3-5% have ventricular arrhythmias warranting cardioversion, a procedure that restores regular heart rhythm. The vast majority of patients experience chest pain, but other symptoms are present including pain in the arm, neck, back, shortness of breath or sweating.

WHO GETS SCAD?
As you probably are aware, SCAD is unusual, accounting for  1-4% of all acute myocardial infarctions or  AMIs (in layman’s terms, heart attacks caused when blood flow to the heart muscle is blocked).  90% of SCAD patients are women between the age 47 and 53; 25-30% of AMIs in women younger than 50 are caused by SCAD, and 15-20% of AMIs during pregnancy or the peripartum are caused by SCAD. Men do have SCAD, but at a lower rate, and physical stressors prior to SCAD are much more common in men than in women. Men are less likely to have emotional stressors or FMD associated with SCAD, too.

WHAT CAUSES SCAD?
In a nutshell, SCAD is likely caused by several associated conditions and twists of genetic fate. Researchers  know some factors play a part:  emotional stress, physical stress, possibly inflammatory disorders, connective tissue diseases, like Ehlers Danlos, Loeys-Dietz syndrome, or Marfan Syndrome, and Fibromuscular Dysplasia (FMD). Suspicion of FMD, in particular, may warrant genetic testing or evaluation. Sex hormones may play a role in SCAD, and have been a focus of attention, but it is unclear how this might happen.

A genetic locus (imagine the “street address” on a gene) called PHACTR1-EDN1, which is associated with migraines and cervical artery dissection, is also associated with SCAD. There are a few other genes that may also affect arteries and be associated with SCAD. Also, a number of clinical investigations suggest that SCAD is one manifestation of FMD or  other arteriopathy in 50% of patients. When the arteries of these individuals are then subjected to shear stress (following physical or emotional stressors, for example) they are vulnerable to dissection.

HOW IS SCAD DIAGNOSED?
Once a potential SCAD patient arrives at the hospital, a troponin test should be initiated. (Troponin is a protein that the heart muscle releases when it is damaged.) Usually, a hospital will administer a troponin test when a patient first arrives at the hospital, and then another one several hours later to assess whether the troponin level has increased. Importantly, Kim found that 27% of initial troponin tests are normal in patients who are later diagnosed with SCAD. This tendency for troponin elevation to show up only in second or third blood tests can contribute to a SCAD diagnosis being missed.

Early diagnosis is important because it can inform treatment options. SCAD is diagnosed with an angiogram, but other imaging tests may be used to further clarify the diagnosis. One of the things an angiogram can reveal is the location of the SCAD and what type of SCAD someone is experiencing.  Because I am about the furthest thing from a cardiovascular imaging expert that you can find, below is a much-simplified description of SCAD types:

Type 1: In this type of SCAD, there is a tear in the lining of the interior blood vessel wall, creating a false lumen.  (Lumen is the term for the space where liquid flows, like the inside of a  garden hose.) A “true” lumen is the passageway through which blood is supposed to flow freely through the veins and arteries. But a dissection creates a “false” lumen – I always think of a Formica countertop in a spot that’s peeled up a bit and traps crumbs—so blood flows into the tear and gets stuck there, because it has nowhere to go. As the blood pools in the false lumen, it takes up more space in the true lumen, ultimately blocking blood flow through the vessel.

Type 2:  In this kind of SCAD, which is most common, there is no tear. A hematoma (i.e., blood clot) forms in the artery wall.  The hematoma then bulges into the true lumen, interfering with blood flow.

Type 3: In what is the least common type of SCAD (and harder to diagnose), a SCAD happens when a hematoma forms in the vessel wall, but on the angiogram it appears shorter than a Type 2 SCAD and can be confused with atherosclerosis.

Type 4: This type of SCAD happens when a hematoma inside the blood vessel wall completely blocks blood flow, rather than just partly obstructing it.

HOW IS SCAD TREATED?
Most patients (more than 80%) can be treated medically. Kim points out that, thus far, guidelines for medical management of SCAD have been developed through expert consensus and data from registries, rather than randomized controlled trials. Nonetheless, we know a lot more about how to manage SCAD than we did only a few years ago.

So, what does medical management involve?

1. The first priority when someone is hospitalized with SCAD, is managing chest pain through medications (nitroglycerin, which dilates blood vessels, calcium channel blockers, which allow the blood vessels to relax and open, or ranolazine, which decreases chest pain). These medications may be useful on an ongoing basis for patients who continue to experience chest pain after their SCAD, too.
2. Conducting testing to see if other issues are present, like ischemia.
3. Once SCAD has been treated, prescribe longer-term medications such as a  beta blocker, which decrease the heart’s activity and allows it to heal.
4. Assess for related vascular abnormalities, like FMD.
5. Help patients get back to healthy life by controlling any hypertension symptoms, providing exercise guidelines, referring to cardiac rehab, managing migraines, if relevant, and/or helping them manage psychosocial difficulties.

Some patients will need to undergo “revascularization,” which is one of several procedures that reopens  the blocked area of the vessel so that blood can flow freely through the true lumen. The decision to pursue a revascularization procedure, like the placement of a stent, is complex, and a physician will consider variables like: the extent of the blockage, which vessel is affected, the patient’s clinical status (i.e., are they getting worse?  are they clinically unstable or at high risk? are they experiencing significant arrhythmia?) as well as other factors. The decision can be a tricky one because the procedures themselves can create risk to the integrity of the blood vessels—in other words, potentially worsen a dissection.

Success rates of procedures like PCI in SCAD patients tend to be lower than in non-SCAD patients in some large studies that Kim cites. Another procedure, called a CABG may also be an option for about 1% of SCAD patients, especially those at particularly high risk for whom PCI and/or medical therapy alone is insufficient. Some SCAD patients will require more high-tech procedures like a mechanical support device that supports or provides the function of the heart. In cases of extreme heart muscle damage or complications,  a heart transplant may be necessary.

In all treatment scenarios, SCAD patients will be monitored on an inpatient basis, usually for 3-5 days, to ensure that  their symptoms are not worsening or recurring. Unfortunately, some SCAD patients do experience a recurrence of their myocardial infarction, as we discussed in the last Research Round-up.

OTHER MEDICATIONS
Anticoagulants:  These medications,  for example, Warfarin, disrupt the body’s ability to form blood clots, but may also worsen bleeding within the artery wall and worsen hematomas. They are typically used for myocardial infarction broadly, and are often administered to SCAD patients, too, even though it is unclear how beneficial they are.  The current consensus is that they should be discontinued after SCAD diagnosis is confirmed.

Antiplatelets:  Antiplatelet agents, like aspirin or clopidogrel, reduce blood clots by preventing blood platelets from sticking together. They may be administered during the acute phase of SCAD, when someone has undergone a PCI procedure (link) or for up to one year following SCAD. The question of whether antiplatelets should be used after 1 year depends on the particular patient.

Beta-blockers, ARBs (angiotensin-receptor blockers), or angiotensin-converting-enzyme (ACE) inhibitors: This group is often used in folks who have had a myocardial infarction, including SCAD. These medications lower blood pressure, thereby decreasing stress on the blood vessels. In one large study that Kim cites, beta blockers significantly decreased the risk of recurrent SCAD. More data is needed regarding the efficacy of beta blockers.

Statins:  These drugs are used frequently for patients with atherosclerotic disease because they lower cholesterol levels that can contribute to plaque build-up in arterial walls. Kim notes that these medications do not have support in the literature for use in SCAD patients, except in patients who also have high cholesterol. Like those who haven’t experienced SCAD, we all are aging and may need to monitor cholesterol, blood pressure, and other cardiac risk factors in the years post-SCAD.

PREVENTING RECURRENCE OF SCAD:
Back in 2020 when the NEJM review was published,  mortality attributable to SCAD was low (1-2%) and the recurrence rates Kim cites are around 17-18% in 3-4 years. (But take heart: remember that more current data has been published so please refer to the first installment of “Research Round-up” for more on recurrence in this link.) Factors are associated with SCAD recurrence include hypertension, FMD, migraine headaches, and tortuosity. Hypertension can be addressed with beta blockers.

Since strenuous physical activity often precedes SCAD, it makes sense to establish limits on heart rate and weight-lifting during exercise. Kim notes that guidelines should be tailored for specific patients, considering their fitness levels and other arterial abnormalities they might have. Generally, patients should avoid isometric exercise, high-intensity training, exercising to the point of exhaustion and prolonged Valsalva maneuvers, which involve bearing down/straining while holding your breath.

PREGNANCY AND SCAD:  There is much to be learned, but Kim notes that data are lacking to establish that pregnancy is a risk factor for SCAD. However, SCAD patients who wish to become pregnant should receive preconception counseling, and, if already pregnant, receive high-risk cardiac care during pregnancy and delivery.

OTHER VASCULAR ABNORMALITIES:  Imaging studies to identify arterial abnormalities should be conducted.  If a patient has FMD, for example, there are published guidelines for the treatment of that condition that should be followed. (For more information on FMD, refer to the Fibromuscular Dysplasia Society of America.)

OTHER RELATED CONDITIONS:  Migraines, anxiety, depression and PTSD should be assessed  and treated by specialists.  Cardiac rehab may help improve emotional symptoms related to SCAD. SCAD patients may benefit from patient organizations and online support communities, like SCAD Alliance.

Thank you for supporting Research Round-up! Please look for another installment next month and if you have ideas for topics you would like to be covered, send a message to info@scadalliance.org.

*Dr. Kim is the Director of the Center for Women’s Cardiovascular Health at Atrium Health, Sanger Heart and Vascular Institute, in Charlotte, NC. In her role with SCAD Alliance she is the chair of our Scientific Advisory Board and the iSCAD Registry Steering Committee. She is also the National Principal Investigator of the iSCAD Registry.