By identifying cardiac fibrosis, cardiovascular magnetic resonance imaging with late gadolinium enhancement proved to be a useful cardiac assessment tool in two studies published in the March 6 edition of JAMA.
In the first, British researchers from London’s Royal Brompton Hospital and elsewhere used cardiovascular magnetic resonance imaging with late gadolinium enhancement [LGE-CMR] to detect and quantify midwall fibrosis in patients with dilated cardiomyopathy. They found that doing so "provided independent prognostic information beyond LVEF" – left ventricular ejection fraction, the basis of current risk stratification schemes –in patients with nonischemic dilated cardiomyopathy.
Separately, American investigators used the same technology in coronary artery disease patients to assess the extent of scarring in their thinned left ventricular walls. They found that "myocardial regions with severe wall thinning do not necessarily consist entirely of scar tissue but instead may have minimal or no scarring," which is inconsistent with current assumptions that thinned regions are made of permanent scar tissue and have no residual viability.
The British group, led by Dr. Ankur Gulati of Royal Brompton Hospital in London, followed 472 patients with dilated cardiomyopathy, assessed at baseline for midwall fibrosis, for a median of 5.3 years.
Thirty-eight of the 142 patients (27%) found to have midwall fibrosis – but only 35 of 330 (11%) without it – died during the trial. Adjusted for LVEF and other conventional prognostic factors, both fibrosis presence (hazard ratio 2.43) and extent (HR, 1.11) were independently and incrementally associated with all-cause mortality. Midwall fibrosis increased by more than five times the likelihood of sudden or aborted cardiac death (JAMA 2013;309:896-908).
LGE-CMR also appeared to "facilitate identification of high-risk patients with milder degrees of left ventricular dysfunction who are currently overlooked by assessment of global left ventricular function alone, Dr. Gulati and colleagues wrote, noting that use of the technology could help guide patient selection for implantable cardioverter defibrillators. Addition of fibrosis to LVEF also significantly improved risk reclassification, they said.
The Duke team, led by Dr. Dipan J. Shah of the Duke Cardiovascular Magnetic Resonance Center in Durham, N.C., followed 201 ischemic heart disease patients with LV wall thinning spanning a mean of 34% of LV surface area; thinning was defined as a diastolic wall thickness at or below 5.5 mm. Thirty seven patients (18%) had had limited or no scar burden, defined as no more than 50% involvement.
Seventy-two of the 201 patients underwent revascularization, including revascularization of the coronary artery supplying the thinned region. Among the 14 limited-scar-burden patients who had repeat CMR-LGE afterward, diastolic wall thickness increased significantly, from 4.4 mm to 7.5 mm; their LV walls were no longer thin. A multivariate analysis showed that the extent of scarring was the strongest predictor of improvement. (JAMA 2013;309:909-18).
The function of the thin walls was also related scar burden. Limited scar burden was "strongly associated with contractile improvement and reversal of wall thinning after revascularization." The results, taken together, showed that as long there is limited scarring, the myocardial wall may thin and revert back to full thickness. Thus, myocardial thinning should not be considered permanent, they concluded.
Most of the 201 patients had significant LV dysfunction and multivessel coronary artery disease. Neither age, sex, cardiac risk factors, angina, heart failure symptoms, nor Q wave presence predicted the amount of scarring.
"The findings suggest that these clinical characteristics should not be used to assess viability in a region of thinning." They also 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," the Duke team concluded.
Members of the British team disclosed grants, consulting arrangements, and other commercial relationships with Biotronik, Boston Scientific, Roche, Servier, Celladon, AstraZeneca, GlaxoSmithKline, GE Healthcare, Bayer, ResMed, Roche Diagnostics, Pfizer, Boehringer, Novartis, Medtronic, Siemens, ApoPharma, AMAG, and Cardiovascular Imaging Solutions.
Two authors on the Duke and Northwestern team are named inventors on a Northwestern University patent for delayed-enhancement cardiovascular magnetic resonance imaging. Another reported speaker fees, consulting deals, or pending grants from Astellas, Siemens, AstraZeneca, Lantheus Medical Imaging, and Takeda.