Prior Silent MI Linked to Tripling of Risk in Acute MI Patients

Patrice Wendling

April 24, 2018

Evidence of a previous silent or unrecognized myocardial infarction (UMI) is concerningly common and independently associated with poor prognosis in patients presenting with a clinical MI, data from an observational study showed.

Silent MI was found by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging in 8.2% of 392 patients presenting with their first acute MI, according to first author, Raquel Amier, MD, from VU University Medical Center, Amsterdam, the Netherlands.

During a mean follow-up of 6.8 years, 41.4% of patients with silent MI and 17.7% of those without silent MI experienced a major adverse cardiovascular event (MACE), and 28.1% vs 10.0%, respectively, died.

After multivariate adjustment, prior MI was associated with more than a threefold increased risk for MACE (hazard ratio [HR], 3.05; 95% CI, 1.64 - 5.70) and all-cause death (HR, 3.69; 95% CI, 1.77 - 7.67), as reported online April 18 in JACC Cardiovascular Imaging.

"What our study shows by these hazard ratios is that it's so important to use the correct technique to look for something," Amier told | Medscape Cardiology. "If you look at the prognostic implications by ECG [electrocardiogram], which we did as well, you don't see a relation but if you then look with CMR at patients with silent MI, then you can make the correct prognostic assessment."

The diagnostic accuracy of ECG was significantly lower than that of LGE-CMR (2.9% vs 8.2%; P  = .002; sensitivity 9.7%, specificity 98%). Q waves on ECG were not associated with MACE or mortality in univariable analyses.

"The other striking thing is that silent MI is unrelated to [acute] infarct size," senior author, Robin Nijveldt, MD, PhD, also with the VUMC, said in an interview. "So whether you have a large or small infarct, this finding even means a lot more than just having a large infarct and that's really intriguing."

Median acute MI infarct size for patients with and without silent MI was 23.8 g and 22.0 g (P  = .71). By contrast, the infarct size of silent MI was 5.1 g (range, 1.4 - 11.5 g).

Previous studies have shown that unrecognized MIs are common and that these patients may represent a high-risk subgroup. However, most studies used routine ECG and were conducted in the general population, the authors noted. LGE-CMR imaging is preferred because it provides tissue characterization, whereas ECG can miss smaller infarctions and not all patients develop Q waves after infarction.

To address this data limitation, investigators reviewed records from 405 patients presenting with acute MI between 2003 and 2013, without a history of prior MI, who underwent 1.5-T LGE-CMR within 14 days of acute MI at two academic centers in the Netherlands. Complete LGE-CMR data were available for 392 patients. MACE data were collected from structured telephone interviews and mortality data from the civil registry.

Patients with silent MI tended to be older than those without silent MI (62 vs 58 years) and more likely to use medication before hospitalization (48% vs 28%).

They were also more likely to have deferred or no reperfusion (19% vs 4% and 13% vs 8%, respectively) but less likely to present with ST-segment MI (84% vs 95%). Cardiovascular risk factors, medical history, infarct-related artery, and number of coronary vessel disease were similar between groups.

During follow-up, patients with silent MI were less likely than those without silent MI to undergo coronary bypass (0% vs 1.9%) and more likely to experience reinfarction (6.3% vs 2.8%) and ischemic stroke (3.1% vs 1.4%), but these differences were not statistically significant.

Diabetes, which has been associated with an increased occurrence of silent MI, was present in just 6% of patients and was not an independent predictor. This may be because the cohort included only patients who eventually presented with an acute MI, thus missing those with diabetes who experience only silent MI or never go to hospital, Amier said.

Overall, the results suggest that silent MI may be useful in risk stratification to guide secondary prevention after an acute MI and could prompt a lower threshold for ischemia detection or coronary angiography should these patients present again with few or atypical symptoms, the authors suggest.

"One of the things that you could say is, 'Well, you should do a CMR in everyone,' but that's just not acceptable and just not doable," Nijveldt said. "Not every hospital has the skills or the scanners to do this and although this is related to worse prognosis, we haven't done any studies so far that we can influence that."

Ultimately, "What you'd really like to do is to prevent even a silent MI from happening," Amier said. "And I think this article shows that we should have a bit more attention to primary prevention."

Notably, the ICELAND MI study revealed that coronary risk factors measured in mid-life are associated with unrecognized MI 31 years later, suggesting an opportunity to modify risk and halt progression, Erik B Schelbert, MD, from University of Pittsburgh School of Medicine, Pennsylvania, and Christopher A Miller, MBChB, PhD, University of Manchester, United Kingdom, write in an accompanying editorial .

They note that the prevalence of UMI exceeded that of recognized MI by about 2 to 1 in elderly patients in ICELAND MI and that a recent Japanese study using LGE-CMR in patients with a first clinical MI corroborated the findings of Amier and colleagues.

The editorialists write: "Given these truly disturbing data, we propose the following recommendations to the cardiology community:

  • Inclusion of CMR with LGE as an endpoint in future therapeutic intervention trials attempting to lower the incidence of MI—both primary and secondary prevention trials. ECG is inadequate. We have concerns that if one does not measure the incidence of UMI in vulnerable patients, one will underestimate the true therapeutic efficacy of the intervention.

  • Primary UMI prevention trials in those at risk, especially the elderly and/or those with diabetes.

  • Secondary prevention trials of risk factor modification in those with UMI."

At a minimum, the cardiology community should strive to accurately phenotype those with known or suspected coronary artery disease, especially the elderly, Schelbert and Miller write.

The authors report no relevant financial relationships. Schelbert has accepted contrast material from Bracco Diagnostics for research purposes and has served on advisory boards for Merck and Bayer. Miller is funded by a clinician scientist award from the National Institute for Health Research, United Kingdom.

JACC Cardiovasc Imaging. Published April 18, 2018. Article, Editorial

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