Correspondence *Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Box 3934, Durham, NC 27710, USA

Email robert.judd@duke.edu

Original article

Kwong RY et al. (2006) Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation 113: 2733–2743   PubMed

Synopsis

Background

Population studies have demonstrated that a high proportion of myocardial infarctions (MIs) go clinically unrecognized, a problem that could be exacerbated by the limited sensitivity of Q waves on electrocardiography. Contrast-enhanced cardiac MRI (CMR) can detect myocardial damage caused by MI with greater sensitivity than electocardiography. The prognostic significance of CMR in patients without a history of MI is, however, unknown.

Objective

To determine the prognostic significance of late gadolinium enhancement (LGE) imaging by CMR in patients with clinical suspicion of coronary artery disease (CAD).

Design

The authors studied a consecutive series of patients with signs or symptoms of CAD who underwent CMR for clinical assessment. Patients with a history of MI, suspected or confirmed myocarditis, infiltrative cardiomyopathy or pericardial disease, and those with unstable angina, hemodynamic instability, or who were in NYHA class IV were excluded from the study.

Intervention

All patients underwent cine steady-state free-precession CMR for assessment of left ventricular (LV) function, and LGE imaging (cumulative 0.15 mmol/kg dose of gadolinium-DPTA) to detect myocardial scarring. Resting 12-lead electrocardiograms were also obtained an average of 8.2 days after CMR. At least 6 months post-CMR, patients were followed up by telephone interview, physician contact, or through hospital records.

Outcome measure

The primary outcome was the occurrence of major adverse cardiac events (MACE), which included cardiac death, new acute MI, unstable angina or heart failure requiring hospitalization, or ventricular arrhythmias requiring discharge of an internal cardioverter-defibrillator.

Results

After a median follow-up of 16 months (range 6–42 months), MACE (including 17 cardiac deaths) had occurred in 31 patients (16% of the total study cohort [n = 195]). When compared with common clinical, angiographic and functional predictors of prognosis, LGE by CMR was the strongest predictor of MACE (hazard ratio, 10.9; P <0.0001). The authors also observed a 'threshold effect' in which patients with the smallest myocardial scars (LGE <2% mean LV mass) had a greater than sevenfold increase in the risk of MACE compared with patients who did not have LGE on CMR (P = 0.0002). The addition of LGE to the models of MACE and cardiac mortality in the multivariate analyses strengthened the prognostic significance of each model beyond that provided by the other variables. LGE remained the most significant predictor of MACE and cardiac mortality in the best overall models (adjusted hazard ratios 5.98, 95% CI 2.68–13.3, and 9.43, 95% CI 3.15–28.3, respectively; P <0.0001).

Conclusion

In patients without a history of MI but with symptoms or signs indicating CAD, LGE by CMR is strongly correlated with MACE and cardiac mortality, and is a more significant prognostic indicator than the common clinical predictors.

Commentary

The LGE technique used by Kwong et al. has been the subject of numerous studies in recent years, many of which address clinical issues such as differentiation between ischemic and nonischemic forms of cardiomyopathy, and the detection of nontransmural infarctions.¹ The paper by Kwong and co-workers, however, is to our knowledge the largest and most systematic study to explore the role of LGE in predicting patient outcome. This seminal contribution raises fundamental questions regarding the prevalence and natural course of unrecognized MI.

The Framingham study established that patients undergoing consecutive bi-annual electrocardiograms could sometimes demonstrate new Q waves, despite not seeking medical attention during the preceding 2 years.² The presence of Q waves was strong evidence that an unrecognized MI had occurred. Unrecognized MI subsequently became a subject of considerable clinical and scientific interest. One important finding of the Framingham study was that the prognoses of patients with unrecognized and recognized MIs were similar, underscoring the need for a sensitive and specific technique to detect MI.

Twenty years on, consensus statements regarding the detection of MI focus on three principle approaches³—serum enzyme markers, electrocardiographic criteria, and symptoms consistent with acute MI. The question of unrecognized MI arises only in the nonacute setting, however, meaning that serum markers, ST-segment elevation, and acute symptoms are not clinically useful. Accordingly, the detection of unrecognized MI is currently based entirely on the presence of Q waves on the electrocardiogram. Defining healed MI on this basis is widely recognized as having a number of important limitations, chiefly that, by definition, all non-Q wave MIs will be missed. Currently, over 50% of recognized MIs in the US are non-Q wave,⁴ implying that over 50% of unrecognized MIs will go undetected.

The Framingham data indicate that 2.82% of men 55–64 years of age have an unrecognized MI detectable by Q waves.² Previous studies have shown that the sensitivity of LGE to detect MI is far higher than that of Q waves, and is comparable with that of serum enzymes.¹ This similarity is probably because, unlike electrocardiography, both serum enzymes and LGE relate directly to myocyte death. Only 7 of the 44 patients with LGE in the Kwong et al. study had detectable Q waves. The true prevalence of unrecognized MI in the general population of 55–64 year old men could, therefore, be as high as 5–10%. Concern about this possibility is heightened by Kwong et al.'s finding that even patients with a very small myocardial scar by LGE (<2% mean LV mass) had a greater than sevenfold increase in MACE.

Approximately 50% of all patients with a first-time MI die before reaching hospital,⁵ but are these really first-time MIs? Would some of these seemingly healthy individuals have shown LGE evidence of unrecognized MI if scanned months or years earlier? Would asymptomatic individuals with positive LGE, but negative enzymes and electrocardiograms, benefit from treatments already in widespread use in patients with recognized MI? The Kwong et al. study, in common with other landmark papers, raises the possibility that contemporary views on the natural progression of CAD are fundamentally incorrect. Future studies to establish the true prevalence of unrecognized MI and to determine its optimal treatment are needed.

Acknowledgments

The synopsis was written by Alexandra King, Associate Editor, Nature Clinical Practice.

References

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Subject areas under which this article appears: Acute coronary syndromes | Imaging and other investigations