Detection of myocardial damage in patients with sarcoidosis

Abstract

Background: In patients with sarcoidosis, sudden death is a leading cause of mortality, which may represent unrecognized cardiac involvement. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can detect minute amounts of myocardial damage. We sought to compare DE-CMR with standard clinical evaluation for the identification of cardiac involvement.

Methods and results: Eighty-one consecutive patients with biopsy-proven extracardiac sarcoidosis were prospectively recruited for a parallel and masked comparison of cardiac involvement between (1) DE-CMR and (2) standard clinical evaluation with the use of consensus criteria (modified Japanese Ministry of Health [JMH] guidelines). Standard evaluation included 12-lead ECG and at least 1 dedicated non-CMR cardiac study (echocardiography, radionuclide scintigraphy, or cardiac catheterization). Patients were followed for 21+/-8 months for major adverse events (death, defibrillator shock, or pacemaker requirement). Patients were predominantly middle-aged (46+/-11 years), female (62%), and black (73%) and had chronic sarcoidosis (median, 7 years) and preserved left ventricular ejection fraction (median, 56%). DE-CMR identified cardiac involvement in 21 patients (26%) and JMH criteria in 10 (12%, 8 overlapping), a >2-fold higher rate for DE-CMR (P=0.005). All patients with myocardial damage on DE-CMR had coronary disease excluded by x-ray angiography. Pathology evaluation in 15 patients (19%) identified 4 with cardiac sarcoidosis; all 4 were positive by DE-CMR, whereas 2 were JMH positive. On follow-up, 8 had adverse events, including 5 cardiac deaths. Patients with myocardial damage on DE-CMR had a 9-fold higher rate of adverse events and an 11.5-fold higher rate of cardiac death than patients without damage.

Conclusions: In patients with sarcoidosis, DE-CMR is more than twice as sensitive for cardiac involvement as current consensus criteria. Myocardial damage detected by DE-CMR appears to be associated with future adverse events including cardiac death, but events were few, and this needs confirmation in a larger cohort.

Figure 1. Enrollment and Protocol

Panel A outlines the enrollment criteria and the four separate steps of the study protocol. Panel B outlines the modified Japanese Ministry of Health (JMH) guidelines for the diagnosis of cardiac sarcoidosis in those with biopsy proven extra-cardiac sarcoidosis. See text for further details.

Figure 2. Patterns of Hyperenhancement in DE-CMR Positive Patients

Images from five patients positive for cardiac involvement by DE-CMR are shown. A variety of hyperenhancement patterns are demonstrated, and these were classified as CAD-type or non-CAD-type depending on whether the left ventricular subendocardium was involved (see text for further details). Cartoon representations of the DE-CMR images are shown immediately adjacent. White (hyperenhanced) regions depict areas of cardiac involvement. The right-most column shows images from repeat DE-CMR scans performed during the follow-up period. These demonstrate the persistence of hyperenhancement.

Figure 3. Comparison of DE-CMR to Autopsy Findings in One Patient

Antemortem DE-CMR study showed two regions of hyperenhancement (orange arrows). The patient died 6 months after DE-CMR. Gross examination of the heart demonstrated aneurysmal dilatation of the LV apex with wall thinning and macroscopically visible scarring. A smaller region of scar tissue was also observed in the lateral wall. These regions matched the areas of involvement seen on DE-CMR. Histological sections prepared from these 2 regions demonstrated dense fibrosis (top, masson trichrome stain) and granulomatous inflammation within patchy fibrosis (bottom, hematoxylin-eosin stain). Examination of the coronary arteries demonstrated the absence of obstructive atherosclerotic disease.

Figure 4. Summary of Cardiac Pathology Evaluation

Cardiac sarcoidosis was diagnosed by pathology evaluation in 4 patients. All 4 had cardiac involvement by DE-CMR. Of the 2 patients with positive endomyocardial biopsy, both had widespread hyperenhancement of the RV side of the interventricular septum (involvement of all 5 septal segments; example, Patient G). Conversely, of 11 patients with negative endomyocardial biopsy, 6 had cardiac involvement by DE-CMR. These 6 had no or limited involvement of the RV side of the interventricular septum (example, Patient H). See text for further details.

Figure 5. Events According to DE-CMR and JMH Status

Panel A outlines adverse events according to DE-CMR and JMH status. Kaplan-Meier curves in Panel B demonstrate event-free and cardiac survival was reduced in patients positive for cardiac involvement by DE-CMR. See text for further details.