Conservative Management, Careful Diagnosis Key for Good SCAD Outcomes

Two new registry studies of spontaneous coronary artery dissection (SCAD) presented at TCT 2021 emphasize the importance of medical therapy and proper diagnosis for this rare but important cause of ACS.

Prior studies have shown that SCAD differs from coronary events caused by atherosclerotic plaque rupture or thrombus in that it is typically caused by an intimal tear in the vessel wall or intramural hematoma. It is underrecognized in practice, more commonly seen in women, and leads to more-frequent hospital readmissions than other causes of acute MI. Additionally, conservative management with aspirin and beta-blockers has demonstrated more effectiveness than angioplasty or stenting.

“Even though all the literature over the last several years has favored medical therapy, there are still some people who don't know how to diagnose SCAD and whose knee-jerk reaction is to place a stent. And that's not the best way to treat these patients,” said Gary Mintz, MD (Cardiovascular Research Foundation, New York, NY), who chaired the featured clinical research session where the SCAD data were presented.

“The thing that impressed me as well as the other panelists was how complementary the two presentations are and how they reinforce the fact that first, in general, patients with SCAD should be treated medically, with stenting reserved for specific high-risk or complicated patients or patients who have SCAD progressing and recurrent MI, that's number one,” he told TCTMD. “Number two, once the patients are treated medically . . . beyond the first month or so, the patients seem to do pretty well.”

CanSCAD Registry

For the first presentation, Jacqueline Saw, MD (Vancouver General Hospital, Canada), showed 3-year findings from the Canadian SCAD cohort study of 750 patients (mean age 51.7 years; 88.5% women; 87.3% Caucasian) with new acute nonatherosclerotic SCAD treated at 22 sites in Canada and the United States between June 2014 and June 2018. About one-third of patients each had no cardiac risk factors and a history of migraine while about one in five each had histories of depression and anxiety. Nineteen patients had incomplete follow-up, with nine completing the study early, seven lost to follow-up, and three withdrawing from the study.

Most patients (91.5%) presented to the hospital with chest discomfort with 31.3% ultimately classified as STEMI. Ventricular tachycardia or fibrillation was documented in 8.3% and baseline EF < 50% in one-quarter. About one-half of patients reported high or severe emotional stress, with 28.9% and 9.8%, respectively, indicating unusually intense physical stress and isometric stress > 50 pounds within the week before. Noncoronary fibromuscular dysplasia (FMD) was identified in about one-third of patients; screening was either incomplete or not conducted in 41.6% of the population.

Optical coherence tomography or IVUS was performed in 7.6% of the cohort, with 13% having multivessel SCAD. The left anterior descending (LAD) artery was the most commonly affected artery and left main or proximal vessel dissection was seen in 7.6%. Type 1 multiple lumen SCAD was identified in 29%, with type 2 SCAD in 60.2% and type 3 in 10.8%. The majority of patients (86.4%) were treated conservatively; 2.3% required revascularization. In total, only 14.1% of patients underwent PCI, with a success/partial success rate of 69.9%.

The most common in-hospital major adverse events were recurrent MI (4.1%), severe ventricular arrhythmia (3.9%), and unplanned revascularization (2.5%). At 3 years, the overall MACE rate was 14%, and that included six deaths (0.8%), 74 recurrent MIs (9.9%), 26 unplanned revascularizations (3.5%), 17 strokes/TIAs (2.3%), and 12 patients with congestive heart failure (1.6%). About half of these events occurred before 14 days. Among the patients with recurrent MI, about one-third (35.1%) were due to extension of SCAD, 21.6% to new de novo recurrent SCAD, and 18.9% to iatrogenic dissection. Additionally, 20.8% of patients visited a cardiac emergency room within 3 years and 7.1% were admitted for chest pain.

The majority of patients were discharged on aspirin (93.7%), beta-blockers (84.8%), and P2Y12 inhibitors (67.4%). At 3 years, most patients remained on aspirin (80%) and beta-blockers (73.5%), with only 7.1% still on P2Y12 inhibitors. A moderate number of patients had recurrent symptoms, with atypical chest pain or typical angina showing up in about 50% at 1 month and remaining in about one-third at 3 years.

On multivariate analysis, the independent predictors of MACE at 3 years included genetic disorders (adjusted HR 5.00; 95% CI 2.18-11.44), being peripartum through 12 months (adjusted HR 2.32; 95% CI 1.17-4.61), and extracoronary FMD (adjusted HR 1.49; 95% CI 1.01-2.20).

Saw commented that the overall MACE rate observed in the study is “very low to what we've seen historically. And this may be due to the fact that the majority of patients remain on aspirin and beta-blockers long term.”

In terms of the recurrent MI events, she explained that “early on they were predominantly due to extension of SCAD, and with follow-up events, recurrent MI was mostly predominantly due to new de novo SCAD. But there are recurrent MIs where patients didn't undergo coronary angiogram, so we couldn't identify the cause of those infarcts, but we would suspect some degree was uncaptured de novo SCAD.”

Nevertheless, Saw continued, “2.4% of new recurrent SCAD over the course of 3 years is really low.” She previously told patients that the risk of recurrent SCAD is between 2% and 5% per year, “and this is less than a third of what we've been used to.”

Commenting on the study, Jennifer Tremmel, MD (Stanford University Medical Center, CA), said “this concept of extension versus de novo is also important.” The timing of imaging may play a role, she suggested, since some patients may be categorized as having had two distinct events, when in fact it may be a continuation of extension of initial SCAD phenomenon.

Saw said they have not yet looked at the timing of the angiograms in the study, “but in our previous studies we know that when you repeat a coronary angiogram within 4 to 6 weeks when you do see further SCAD it is typically due to the extension of the original SCAD lesion as opposed to a new SCAD in an entirely different site.” New de novo SCAD tends to show up “later, much beyond the 1-month time point.”

Tremmel suggested that CT might then begin to play a more-important role compared with coronary angiography in terms of reevaluation.

That’s a valid point, Saw said, “because we know that the risk of iatrogenic catheter-induced dissection is not rare in these patients, and so I think if you are doing a repeat angiogram to look for healing, you probably shouldn't do it unless there are good clinical reasons behind it. . .  But even if they have atypical symptoms, we tend not to repeat the coronary angiogram anymore.” CT might also be good for assessing “some degree of healing” in patients with large-vessel SCAD, she added. “I might favor that versus doing a repeat coronary angiogram in those cases.”

Spanish Data

In his presentation, Marcos García-Guimarães, MD (Hospital del Mar, Barcelona, Spain), showed long-term follow-up results from the prospective Spanish registry on SCAD. He called SCAD “a rare but well-recognized cause” of ACS, but said few prospective data sets exist, and most are from outside Europe.

The registry included 389 patients (88% women; mean age 53 years) with 441 SCAD lesions treated at 34 Spanish hospitals between June 2015 and December 2020. Patients presented primarily with NSTEMI (54%), and the LAD was the most commonly affected artery (44%). SCAD lesions were mostly observed in distal segments (38%) and secondary branches (54%), with 11% having multivessel SCAD, and type 2 SCAD was the most frequent on angiography (62%). Clinical follow-up at 6 months was available in 355.

Conservative management was indicated in 78% of patients, with PCI success documented in 84% of the 84 patients who underwent the procedure. Most (93%) were discharged on aspirin, with dual antiplatelet therapy (DAPT) prescriptions in 58% and beta-blockers in 80%.

In-hospital major adverse events were recorded in 6.4% of patients, driven by nonfatal reinfarction (2.8%) and unplanned revascularization (4.4%). During a median follow-up of 29 months, the MACCE rate was 13%, and that included nine deaths (2.5%), 27 nonfatal acute MIs (7.6%), 22 unplanned revascularizations (6.2%), seven SCAD recurrences (2%), and four strokes (1.1%). Sixty percent of the recurrent MIs and 77% of new revascularizations were reported within the first 30 days.

Multivariate analysis showed history of hypothyroidism (HR 3.45; 95% CI 1.67-7.32), proximal involvement (HR 2.72; 95% CI 1.29-5.77), and DAPT on discharge (HR 2.28; 95% CI 1.08-4.83) to be independent predictors of MACCE on follow-up.

The data from both of these studies “reminds us that the option for the majority of patients with SCAD is conservative management and only a few percent of patients require PCI initially,” García-Guimarães said. Also, he noted, the rate of recurrence in both studies was “quite low and most of the events were during the first month after the index event.”

DAPT seems to be related to a “higher risk of early events after SCAD and the meaning of this or the reason we think is probably explained by the pathophysiology of the patients,” García-Guimarães continued.

During the discussion, panelist Mauricio Cohen, MD (University of Miami Hospital and Clinics, FL), said “it's striking to see how much those two studies overlapped in terms of cardiovascular risk factors, age of the patients, gender, and then the rates of events.” He questioned, however, what to do with respect to hypothyroidism as a risk factor as “we actively look for it, but then we find it and we don't know how to treat that and how to react to that.”

García-Guimarães said the relationship between hypothyroidism and events is likely due to “some structural changes in the coronary artery wall that probably make this patient more prone to the phenomena of dissection,” but he did not indicate how to treat these patients any differently.

‘Think About the Diagnosis’

Future research in this space should focus on the best pharmacologic approach to treating SCAD, Mintz said. “In the Canadian study, the patients were on beta-blockers and aspirin and that seemed to be good therapy. In the Spanish study, in the multivariate analysis, DAPT was a predictor of adverse outcomes. We don't know if those were the stented patients or the medically treated patients, so I think we don't know the best medical therapy or the best pharmacologic therapy for the patients who don't get stented. And that should be the majority of patients.”

Until more data become available, he said he would follow what was done in the Canadian registry “because I think they have the best data and their patients are treated with aspirin and beta-blockers.”

As for identifying SCAD in the first place, Mintz said “most of the time you can make the diagnosis or suspect the diagnosis angiographically, but not everybody has been trained to do so.” Advanced imaging, be it intracoronary or CT, “can help in questionable cases,” he continued, but ultimately, he urged clinicians to consider SCAD at the outset. “If you don't think about the diagnosis, you won't make the diagnosis.”