2 imaging studies offer intrigue but clinical gain remains in doubt

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Two separate studies edged delayed-enhancement cardiovascular MRI toward the clinical equivalent of home plate, but neither scored a run. The studies and an accompanying editorial were published March 6 in the Journal of the American Medical Association.

Ankur Gulati, MD, of Royal Brompton Hospital in London, and colleagues assessed the prognostic value of midwall fibrosis with late gadolinium enhancement cardiovascular MR (LGE-CMR) to predict adverse outcomes for patients with dilated cardiomyopathy. This condition may lead to progressive heart failure and sudden cardiac death (SCD); consequently, risk stratification beyond assessments based on left ventricular ejection fraction (LVEF) may help physicians tailor management plans, including selecting patients for implantable cardioverter-defibrillators (ICDs).

“Most patients who experience SCD do not have severely reduced LVEF, and many patients with significant impairment of LVEF may still be at low risk for SCD,” they wrote. About one-third of these patients have a characteristic midwall pattern of replacement fibrosis detected by LGE-CMR, which the authors suggested might be a predictor of mortality and SCD.

To test that hypothesis, they designed a prospective longitudinal study that enrolled 472 consecutive patients with dilated cardiomyopathy who were referred to their hospital between 2000 and 2008. The patients underwent LGE-CMR to evaluate the presence and extent of midwall fibrosis, with follow-up through December 2011. The primary endpoint was all-cause mortality and the secondary endpoints were cardiovascular mortality or heart transplantation, the composite of SCD or aborted SCD and the composite of heart failure, heart failure hospitalization and heart transplant.

Two independent readers who were blinded to clinical data assessed the presence of midwall fibrosis and an experienced operator quantified the extent of fibrosis. They verified deaths through national resources, death certificates and communications with physicians and families.

Patients had a mean LVEF of 37 percent and were followed for a median duration of 5.3 years. Thirty percent had midwall fibrosis with a median extent of 2.5 percent. The mortality rate for patients with midwall fibrosis was 26.8 percent compared with 10.6 percent for patients without midwall fibrosis and the presence of midwall fibrosis was associated with a higher risk of cardiovascular mortality or transplantation. Patients with midwall fibrosis had higher rates of SCD or aborted SCD (29.6 percent vs. 7 percent) and higher rates of the heart failure composite (25.4 percent vs. 11.2 percent).

Adding midwall fibrosis to a risk model decreased the mortality risk for patients with an LVEF of 35 percent and no midwall fibrosis from 12.7 percent to 9.4 percent and increased mortality risk for patients with midwall fibrosis from 12.7 percent to 19.9 percent. Twenty-nine percent of patients were correctly reclassified with the addition of midwall fibrosis status, Gulati et al determined.

“The addition of midwall fibrosis to LVEF resulted in significant improvements in risk reclassification for both all-cause mortality and the arrhythmic composite,” they wrote. “Our findings suggest that detection and quantification of midwall fibrosis by LGE-CMR may represent useful markers for the risk stratification of death, ventricular arrhythmia and HF [heart failure] for patients with dilated cardiomyopathy.”

They added that the information provided by imaging could help in identifying patients at high risk who would benefit from ICD implantation.

In the second study, Dipan J. Shah, MD, of the Duke Cardiovascular Magnetic Resonance Center in Durham, N.C., and colleagues evaluated patients with regional myocardial wall thinning to assess if they have minimal or no scarring using LGE-CMR. They suggested that such regions might represent viable myocardium. They enrolled 1,055 patients with coronary artery disease who underwent LGE-CMR imaging at three centers between 2000 and 2008.

The study was divided into three parts: first, to determine the prevalence of regional thinning; second, to evaluate the prevalence of limited scar burden (less than 50 percent) in thinned myocardium; and third, to evaluate the relationship between scar burden and functional burden and tissue remodeling in patients who received coronary revascularization.

Nineteen percent of the patients had myocardial wall thinning with thinning of a substantial (a mean of 34 percent) portion of the left ventricle (LV). Of those with wall thinning, 18 percent had scarring of less than 50 percent.

Seventy-two percent of patients underwent revascularization. Shah et al reported inverse relationships between the extent of scarring and contractile improvement after revascularization as well as myocardial remodeling, with only those patients with limited scar burden showing improvement. Based on those findings, they suggested that myocardial thinning may be reversible.

“[W]e have shown that the myocardial wall may thin and revert back to full thickness as long as limited scarring is present,” they wrote. “These results indicate that the end stage of remodeling is better determined by tissue composition (i.e., scarring) rather than any set level of morphological changes to the LV cavity or LV wall.”

In an accompanying editorial, Deepak K. Gupta, MD, Raymond Y. Kwong, MD, MPH, and Marc A. Pfeffer, MD, PhD, all of Brigham and Women’s Hospital in Boston, pointed to limitations in both studies. As a single center study using low-risk patients, Gulati et al’s findings may not apply to those patients who would most benefit from risk stratification, they wrote, and the study by Shah et al was subject to referral and selection bias.

“Collectively, these and other studies demonstrate that CMR with LGE imaging adds to the practitioner’s armamentarium for assessment of cardiac structure and function and augments diagnostic and prognostic capabilities,” the editorial writers offered.

But determining which patients to evaluate remained a challenge. “At this point, for the practicing physician, the incremental information gained from CMR with LGE imaging from these two studies, albeit novel and supportive, is not yet sufficient to alter clinical practice guidelines,” they concluded.