ľֱ

Scarring of Damaged Heart Muscle Predicts Death

MedpageToday

This article is a collaboration between ľֱ and:

Fibrosis seen on enhanced cardiac MRI helps predict mortality among patients with dilated, nonischemic cardiomyopathy, a longitudinal study showed.

Midwall fibrosis was associated with a nearly threefold higher mortality risk over about 5 years of follow-up in this population, with a rate of 27% versus 11% in patients without fibrosis (P<0.001), Sanjay K. Prasad, MD, of the Royal Brompton Hospital in London, and colleagues found.

When added to left ventricular ejection fraction, presence of fibrosis significantly improved risk reclassification for all-cause mortality as well as for a sudden cardiac death composite, they reported in the March 6 issue of the Journal of the American Medical Association.

Action Points

  • Note that this prospective cohort study demonstrated a strong association between myocardial fibrosis (detected by cardiac MRI) and all-cause mortality.
  • Be aware that the study population was relatively healthy, with a plurality of patients having NYHA class 1 symptoms.

"Identification of better independent prognostic factors is necessary to enable clinicians to more accurately stratify risk in patients with dilated cardiomyopathy and tailor management accordingly."

"Risk stratification in dilated cardiomyopathy," they wrote, "constitutes a crucial part of patient management with implications for surveillance, treatment, and outcome" -- particularly who gets an implantable cardioverter-defibrillator (ICD).

But data from a single-center is not robust enough to support changing clinical practice, such as adding midwall fibrosis to determinations for ICD implantation, Marc A. Pfeffer, MD, PhD, of Harvard and Brigham and Women's Hospital, and colleagues cautioned in an accompanying editorial.

"With only 57% of patients with New York Heart Association functional class II or III, the study ... was not powered nor designed to investigate the additional benefit of cardiac MR beyond current class I indications for cardioverter-defibrillator therapy in dilated cardiomyopathy patients," they wrote.

Also, the study included a low-risk population compared with other cardiac MRI studies, so "whether the conclusions drawn from this cohort represent those dilated cardiomyopathy patients most in need of risk stratification is uncertain," they added.

Another problem was that the reclassification analysis didn't include other proven and more readily available risk markers, such as recent hospitalization and renal function, the editorial explained.

The prospective study included 472 consecutive patients with dilated cardiomyopathy seen at a single center for late gadolinium enhancement cardiovascular MRI over a 1 month period, among whom 142 (30%) had midwall fibrosis.

During a median 5.3 years of follow-up, the presence of fibrosis predicted several adverse outcomes along with mortality.

The secondary composite endpoint of cardiovascular mortality or cardiac transplantation occurred in 29% of patients with midwall fibrosis versus 8% among patients without fibrosis (P<0.001).

Midwall fibrosis predicted 3.2-fold elevated risk of that endpoint after adjustment for other significant prognostic variables.

The odds were also 3.8-fold higher for getting an ICD and 2.4-fold higher for getting a pacemaker-defibrillator combination device among midwall fibrosis patients, both statistically significant.

Midwall fibrosis was associated with an adjusted 4.6-fold higher risk of the composite of sudden cardiac death or appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia arrhythmic (rate 30% versus 7%, P<0.001).

The composite of heart failure death or hospitalization or cardiac transplantation was also independently 62% more likely to occur with midwall fibrosis (rate 25% versus 11%, P=0.049).

Extent of midwall fibrosis was also a significant predictor on all the measures, "suggesting that not only the presence but also the burden of replacement fibrosis is an important determinant of outcome."

The addition of fibrosis status appeared to make a "sizable" contribution to ejection fraction-based risk stratification for all the endpoints, the researchers noted.

It correctly reclassified 26% of patients in terms of all-cause mortality risk and 29% of patients in terms of the sudden cardiac death composite (P=0.001 and P=0.002, respectively).

The researchers acknowledged that corroboration of the findings in a multicenter study is needed.

While referral bias was possible in the cohort of patients referred clinically for cardiac MRI, confounding of outcomes by availability of cardiac MRI wasn't likely since guidelines for heart failure don't recommend specific treatment based on midwall fibrosis, they noted.

From the American Heart Association:

Disclosures

The study was supported by the National Institute for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College, London.

Prasad reported receiving grant support from the British Heart Foundation, CORDA, and Rosetrees Trust, and the National Institute for Health Research; and receiving speaking fees from Bayer Schering.

The editorialists reported having no conflicts of interest to disclose.

Primary Source

Journal of the American Medical Association

Gulati A, et al "Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy" JAMA 2013; 309: 896-908.

Secondary Source

Journal of the American Medical Association

Gupta DK, et al "Cardiovascular imaging in clinical practice what does late gadolinium enhance?" JAMA 2013; 309: 929-930.