Mortality, myocardial infarction risks argue for aggressive prevention strategies

Patients with suspected coronary artery disease (CAD) who had unrecognized myocardial infarction (UMI) detected by stress cardiac magnetic resonance (CMR) imaging may have increased risk for recurrent MI and excess all-cause mortality, a post-hoc analysis of SPINS data suggested.

“CMR imaging can detect clinically unrecognized myocardial fibrosis in approximately 15% of patients with suspected CAD,” wrote Raymond Kwong, MD, MPH, of Harvard University, and coauthors in Journal of the American College of Cardiology. “Like clinically evident myocardial infarction, occult myocardial damage is associated with subsequent MI and all-cause mortality, independently of ischemia or left ventricular ejection fraction.”

In models adjusted for ischemia and left ventricular function — which was lower in patients with UMI than those with clinically recognized myocardial infarction (RMI) — both UMI and RMI were associated with increased risk of death or myocardial infarction, with HRs of 1.82 (95% CI 1.37-2.42) and 1.54 (95% CI 1.14-2.09), respectively.

The risk for heart failure-related hospitalization was higher for those with UMI compared with the RMI group, with HR 2.60 (95% CI 1.48-4.58; P < 0.001).

“The high prevalence of UMI by CMR argues for the evaluation of more aggressive MI prevention strategies and illustrates the limitations of current primary prevention strategies that ignore UMI,” wrote Erik Schelbert, MD, of the University of Pittsburgh, and coauthors, in an accompanying editorial.

The editorialists identified two novel observations in the study: first, that ischemia did not mediate the association between UMI and major adverse cardiac events, “contrary to conventional wisdom,” they wrote.

“This finding aligns with recent cardiac CT angiography data showing that plaque burden associates with additional risk of major adverse cardiac events regardless of coronary stenosis ≥50%, a surrogate for myocardial ischemia,” they said. “Because UMI indicates higher plaque burden as quantified by coronary calcium, UMI patients have more extensive coronary disease, which increases the risk of major adverse cardiac events.

“Second, UMI patients exhibited lower use of guideline-directed medical therapies,” they continued. “These compelling data indicate undertreatment of patients with UMI and highlight an opportunity to improve outcomes with more aggressive medical therapies. Whether the diagnosis of UMI leads to intensified medical therapy and improves patient care requires further study, but seems likely.”

In some populations, UMI may be more prevalent than RMI. Prior work has shown comparable outcome risks associated with RMI and UMI for all-cause and cardiovascular death, MI, and heart failure hospitalization; myocardial ischemia had been thought to account for unfavorable risks associated with UMI.

Kwong and colleagues studied a consecutive cohort of 2,349 patients with suspected CAD (referred for evaluation of chest pain, dyspnea, abnormal ECG, or other clinical presentation suggestive of CAD as determined by the treating clinician) who had stress CMR in the SPINS study between January 2008 and December 2013. Participants had mean age of 63 and 53% were male, with median follow-up of 5.4 years.

Prevalence of UMI and RMI were 14.5% and 15.2%, respectively. UMI and RMI groups had similar cardiovascular risk factors including age, sex, hypertension, diabetes, smoking, and family history of CAD.

On stress CMR, those with UMI had significantly lower left ventricular ejection fraction (P<0.001). Rates of inducible ischemia were about one-third in both groups.

At the time of CMR, those with UMI were less likely to be taking aspirin (63% vs 84%; P < 0.001), statin (62% vs 82%; P < 0.001), or a beta-blocker (63% vs 74%; P = 0.002). Angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker treatment rates were similar. Of those who did not have documented CAD prior to the study, 55% were taking aspirin and 52% a statin.

“In keeping with previous studies, patients with UMI, compared with patients without MI, had significantly higher rates for death and/or MI and major adverse cardiac events,” Kwong and coauthors wrote.

“We observed a 2-fold rate for all-cause mortality, 4-fold rate for CV death, 4-fold rate for heart failure hospitalization, and 3-fold rate for nonfatal MI, and those rates remained practically unchanged after exclusion of patients with CMR-detected ischemia,” they added. “Those findings indicate that the prognostic value of UMI is independent of the presence of underlying ischemia and may have important implications in our understanding of UMI pathophysiology, since undetected, silent ischemia is currently considered to be the prime driver of adverse outcomes in UMI.”

“Overall, the SPINS study affirms the concept that UMI detected by (stress) CMR represents advanced, aggressive coronary disease, the myocardial imprint of previous vulnerable coronary atherosclerosis,” the editorialists noted. “Beyond the narrow focus on ischemia, a more holistic and patient-centered approach for risk stratification in patients with suspected coronary disease should include robust detection of UMI.

Limitations of the study include its retrospective design that could not include patient management following CMR, including information about medications.

  1. Be aware that imaging detected unrecognized myocardial fibrosis in roughly 15% of patients with suspected CAD.

  2. Future studies should further assess the clinical impact of CMR guidance using combined ischemia and occult myocardial damage towards patient management.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The SPINS (Stress CMR Perfusion Imaging in the United States) study of the SCMR (Society for Cardiovascular Magnetic Resonance) registry was funded by the SCMR, using a research grant jointly sponsored by Siemens Healthineers (Erlangen, Germany) and Bayer AG (Leverkusen, Germany).

Kwon reported no disclosures.

Schelbert has accepted contrast material from Bracco Diagnostics for research purposes and has served on advisory boards for Merck, Bayer, and Haya Therapeutics.

Cat ID: 2

Topic ID: 74,2,730,2,308,358,913,914,192,925