CV Mortality High With Type 2 MI

Debra L. Beck

March 05, 2020

Among individuals aged 50 years or younger who experienced an initial myocardial infarction (MI), those with type 2 MI had significantly higher long-term all-cause and cardiovascular mortality compared with those who experienced type 1 MI, a retrospective cohort study shows.

Nearly half of patients with myocardial injury and more than one third of those with type 2 MI died within 10 years of the index event.

"Perhaps the all-cause mortality rate is not unexpected because, by definition, to have a type 2 MI, you have to have supply-demand mismatch, which means you have underlying medical issues," said senior author Ron Blankstein, MD, Brigham and Women's Hospital, Boston, Massachusetts, in an interview.

"But one of the really important findings here is that despite their young age and presumably low risk of coronary artery disease, the patients with type 2 MI had a higher rate of cardiovascular mortality as compared to those with type 1 MI, so they're not just dying from the underlying medical illness that may have triggered the MI but from cardiovascular causes," he added.

Blankstein and colleagues, including first author Avinainder Singh, MD, Yale University, New Haven, Connecticut, conducted a retrospective cohort study to compare the clinical characteristics, management, and long-term outcomes of young adults who had experienced a first MI.

Their findings were published online in the March 10 issue of the Journal of the American College of Cardiology.

Included in the analysis were 3829 adults aged 50 years or younger whose troponin level at presentation was higher than the 99th percentile or who received a diagnosis of MI in accordance with the International Classification of Diseases. The period of the study was 17 years. The median age of the participants was 44 years, and 30% of the population were women.

Slightly more than half (55%) of eligible enrollees were adjudicated to have type 1 MI; 32% had type 2 MI; and 13% had myocardial injury.

Determination was based on the definition in the Fourth Universal Definition of Myocardial Infarction (UDMI), which distinguishes patients with MI from those with nonischemic myocardial injury. Type 2 MI is defined as an imbalance between myocardial oxygen supply and demand unrelated to acute coronary atherothrombosis. Myocardial injury has a similar mismatch driven by a secondary factor, but there is no overt clinical evidence of myocardial ischemia, the authors note.

During a median of 10.2 years of follow-up, mortality was 12% in the type 1 group, 34.2% in the type 2 group, and 45.6% for those with myocardial injury (P < .001).

Among patients with type 2 MI, the most common causes were sepsis (16.2%), arrhythmias (14.5%), and hypoxia and/or respiratory failure (11.5%). For those with myocardial injury, the most common causes were sepsis (24.1%), hypoxia and/or respiratory failure (20.1%), and hypotension (10.5%).

The cardiovascular mortality rate was 6.0% for type 1 MI, 8.7% for type 2 MI, and 4.7% for myocardial injury.

After adjustment for demographic and treatment factors, type 2 MI was deemed the most deadly in the long term, with adjusted hazard ratios of 1.8 for all-cause mortality (P = .004) and 2.7 for cardiovascular mortality (P = .003; both compared to type 1 MI).

"Whenever there are acute medical issues going on, there is generally an increased stress on the body and the heart has to work harder, setting things up for a supply-demand mismatch," explained Blankstein.

"Traditionally, we think that in these younger individuals with acute medical issues, their hearts are healthy and can increase cardiac output to meet demand, but what we saw here is that maybe these individuals actually have underlying coronary artery disease, and they're not just at risk from these medical issues but also from underlying cardiovascular disease," said Blankstein.

Patients with type 2 MI were less likely to receive secondary preventive medications on discharge compared to those with type 1 MI.

Type 2 MI and Myocardial Injury: Maturing Clinical Entities

In an interview, Nicholas Mills, MD, from the Royal Infirmary of Edinburgh, Scotland, United Kingdom, commented on the researchers' emphasis on younger patients.

"This is a very unique cohort in that the investigators specifically recruited young adults under the age of 50 who, it was assumed, would have a lower pretest probability of having coronary artery disease," he said. He noted that the finding of type 2 MI in about one third of patients alerts clinicians to the need to better understand this entity.

"Whilst many clinicians have heard of the concept of type 1 and type 2 MI, in their clinical practice, they continue to diagnose people as non-STEMIs [non-ST-elevation MIs] or STEMIs, and if they find troponin elevation in another setting, they tend to ignore it," said Mills.

The reasons for this, he said, likely have to do with some continued uncertainty and lack of familiarity with the diagnostic criteria for type 2 MI and myocardial injury and because there are no guidelines for evaluating or treating these patients.

"I think we have an opportunity through education and dissemination of important research like this to broaden the recognition of this concept and encourage practicing clinicians to at least consider what the next steps might be for someone with type 2 myocardial infarction," said Mills.

"A decade ago, people called these type 2 MIs 'troponin leaks' or 'tiny MIs in the setting of other medical events,' " said Blankstein. This trial, along with previous studies that show both the short-term and long-term hazards of these events, drive home the point that these clinical entities should not be ignored, he suggested.

"Our findings suggest that when patients have a type 2 MI, we need to understand that they're at higher risk of cardiovascular mortality and accordingly consider preventative therapies that we often only give type 1 MI patients, such as lipid-lowering therapies, aspirin, and other antithrombotic treatments," said Blankstein.

In an editorial, Kristian Thygesen, MD, DSc, Aarhus University, Denmark, and Allan Jaffe, MD, Mayo Clinic, Rochester, Minnesota, advocate that "any patient, young or old, with type 2 MI or myocardial injury deserves a basic cardiac evaluation...."

It is particularly important, they write, that the cardiology community better understand how to diagnose and manage these clinical entities now that high-sensitivity troponin assays are becoming more widely available. This study predated widespread use of high-sensitivity troponin assays.

The UDMI has been around for about 20 years but remains a work in progress. A key change from the Third UDMI definition to the Fourth UDMI definition — released in August 2018 — was the determination that a diagnosis of myocardial injury should be reserved for cases in which there is evidence of elevated cardiac troponin values with at least 1 value above the 99th percentile upper reference limit.

Type 2 MI is determined by a risk and/or fall in cardiac troponin values above the 99th percentile and evidence of an imbalance between myocardial oxygen supply and demand unrelated to acute coronary atherothrombosis, with evidence of ischemia (symptoms of acute myocardial ischemia, ECG changes, evidence of new loss of viable myocardium or new regional wall motion abnormality).

It is hoped that an ongoing study will help clinicians better understand the importance of careful management of type 2 MI. Mills is the principal investigator for the DEMAND-MI (Determining the Mechanism of Myocardial Injury and Role of Coronary Disease in Type 2 Myocardial Infarction) trial, which will enroll 100 patients with type 2 MI. Participants will undergo comprehensive cardiac imaging, including MRI.

"We're going to try and dispel the myth that these are just troponin leaks and demonstrate the underlying cardiac pathology that these patients have," said Mills. He noted that the term "troponin leak" downplays the condition and may lead to underdiagnosis and undertreatment.

"It's going to be an absolute eye-opener.... I think if people knew how many of these patients have really substantial and important underlying heart disease, they'd be shocked," he added.

The DEMAND-MI investigators hope to present their findings at the European Society of Cardiology meeting in late August.

Blankstein has received research support from Amgen and Astellas. Mills is funded by the British Heart Foundation and has received honoraria from Abbott Diagnostics, Siemens Healthineers, and Roche Diagnostics, and the University of Edinburgh. He has also received research grants from Abbott Diagnostics and Siemens Healthineers. Thygesen has disclosed no relevant financial relationships. Jaffe has been a consultant for Beckman, Abbott, Siemens, ET Healthcare, Roche, Aphingotec, Quidel, Brava, Sphingotec, Blade, and Novartis.

J Am Coll Cardiol. 2020;75:1003-13. Abstract, Editorial

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