More Liberal Definition of Type 2 MI May Misclassify Some Patients

Not requiring the presence of CAD as part of the definition identifies patients with a very low risk of 90-day cardiovascular mortality.

More Liberal Definition of Type 2 MI May Misclassify Some Patients

Patients diagnosed with type 2 MI in the absence of CAD may not have type 2 MI at all, authors of a new analysis suggest.

In a cohort of patients presenting to the emergency department with symptoms indicative of MI, those diagnosed with type 2 MI despite not having clinically evident coronary disease had a very low rate of mortality. In fact, none of these patients died of cardiovascular causes within the first 90 days, according to lead author Thomas Nestelberger, MD (University Hospital Basel, Switzerland), and colleagues.

That rate of cardiovascular mortality was similar to that seen in patients with noncardiac causes of chest pain (0.2%) but significantly lower than rates observed in patients diagnosed with type 1 MI (4.8%) or with type 2 MI using a stricter definition that requires the presence of CAD (3.7%), the researchers report in study published in the September 26, 2017, issue of the Journal of the American College of Cardiology.

“We should reclassify these patients if there is no underlying coronary artery disease, and I think that they are now misclassified as a type 2 myocardial infarction because they have a more benign mortality rate compared to patients with underlying coronary artery disease,” Nestelberger told TCTMD.

In an accompanying editorial, however, James Januzzi, MD (Massachusetts General Hospital, Boston, MA), and Yader Sandoval, MD (Mayo Clinic, Rochester, MN), question whether short-term mortality risk is all that matters when it comes to classifying MIs.

“Contrary to establishing a more restrictive definition of MI requiring CAD, we would emphasize that certain groups of patients, in particular women, can indeed present with MI in the absence of obstructive atherosclerotic CAD, and even with normal coronaries,” they write. “Patients with spontaneous coronary artery dissection present unequivocally with acute MI in the absence of CAD, yet numerous series show a low mortality, some reporting a death rate of 0% at short-term follow-up.”

They ask whether those patient groups should be considered to not have MI based on low mortality.

Although we agree in principle that type 2 MI without CAD likely has a more benign course, we do not support reconsideration of their diagnosis—this should be considered just one of many causes of type 2 MI, and one with a possibly less malignant outcome.”

Uncertainty in the Universal Definition

According to the universal definition of MI released in 2007 and reaffirmed in 2012, type 2 MI is diagnosed when there is an imbalance between myocardial oxygen supply and/or demand that is not caused by atherosclerotic plaque disruption. There is controversy, however, about whether CAD needs to be present to establish a diagnosis of type 2 MI, Nestelberger et al note, pointing out that the 2007 version of the universal definition might be interpreted to require the presence of CAD while the 2012 version might be seen as allowing diagnosis of type 2 MI in patients without CAD.

To explore the potential impact of those discrepant interpretations, the investigators turned to the ongoing APACE (Advantageous Predictors of Acute Coronary Syndromes Evaluation) study, which is recruiting patients presenting to the emergency room with symptoms suggestive of MI at 12 centers in five European countries. The analysis included 4,015 patients for whom a final diagnosis could be adjudicated.

Based on the stricter definition requiring the presence of CAD, 2.8% of patients had a type 2 MI. The rate was more than doubled (to 6%) when using the more liberal standard not requiring the presence of CAD, however. The 128 patients who only met criteria for type 2 MI using the latter definition were deemed the reclassified cohort; most had tachyarrhythmias (73) or hypertensive crises (38).

The use of treatments known to improve MI outcomes differed significantly between reclassified patients and those with type 2 MI based on the stricter definition, with reclassified patients having lower rates of coronary revascularization (0.8% vs 6.3%), discharge dual antiplatelet therapy (1.6% vs 22.0%), and discharge high-dose statins (31% vs 71%; P < 0.01 for all).

“This supports the concept that the optimal treatment for type 2 MI patients will depend on the underlying cause of the supply-demand mismatch,” Nestelberger said.

He and his co-authors conclude, “A more restrictive definition of [type 2 MI] that requires CAD could facilitate development of better management strategies and clarify the benefit of secondary prevention measures and coronary revascularization for patients who experience these events.”

In their editorial, Januzzi and Sandoval “propose investigating type 2 MI using a phenotype-specific approach; this framework is similar to that of another heterogeneous diagnosis: heart failure with preserved ejection fraction. Only with a clear understanding of the spectrum of type 2 MI can we approach the development of treatment options for this frequently encountered and often deleterious condition.”

Sources
Disclosures
  • The study was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, University Hospital Basel, Abbott, Brahms, Beckman Coulter, Biomerieux, Roche, Nanosphere, Siemens, 8sense, Bühlmann, and Singulex.
  • Januzzi reports receiving grants from Roche Diagnostics, Siemens, Singulex, Abbott, and Prevencio; serving as a consultant for Roche Diagnostics, Abbott, and Critical Diagnostics; and having served on the endpoint committee for Boehringer Ingelheim, Pfizer, Abbvie, and Janssen.
  • Nestelberger and Sandoval report no relevant conflicts of interest.

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