Effectiveness of late gadolinium enhancement to improve outcomes prediction in patients referred for cardiovascular magnetic resonance after echocardiography

Abstract

Background: Echocardiography (echo) is a first line test to assess cardiac structure and function. It is not known if cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) ordered during routine clinical practice in selected patients can add additional prognostic information after routine echo. We assessed whether CMR improves outcomes prediction after contemporaneous echo, which may have implications for efforts to optimize processes of care, assess effectiveness, and allocate limited health care resources.

Methods and results: We prospectively enrolled 1044 consecutive patients referred for CMR. There were 38 deaths and 3 cardiac transplants over a median follow-up of 1.0 years (IQR 0.4-1.5). We first reproduced previous survival curve strata (presence of LGE and ejection fraction (EF) < 50%) for transplant free survival, to support generalizability of any findings. Then, in a subset (n = 444) with contemporaneous echo (median 3 days apart, IQR 1-9), EF by echo (assessed visually) or CMR were modestly correlated (R(2) = 0.66, p < 0.001), and 30 deaths and 3 transplants occurred over a median follow-up of 0.83 years (IQR 0.29-1.40). CMR EF predicted mortality better than echo EF in univariable Cox models (Integrated Discrimination Improvement (IDI) 0.018, 95% CI 0.008-0.034; Net Reclassification Improvement (NRI) 0.51, 95% CI 0.11-0.85). Finally, LGE further improved prediction beyond EF as determined by hazard ratios, NRI, and IDI in all Cox models predicting mortality or transplant free survival, adjusting for age, gender, wall motion, and EF.

Conclusions: Among those referred for CMR after echocardiography, CMR with LGE further improves risk stratification of individuals at risk for death or death/cardiac transplant.

Figure 1

Generalizability is important for newer imaging modalities, and our survival data of consecutive patients stratified by cardiovascular magnetic resonance (CMR) findings reproduced the results of others. Our data (n = 1044) in panel A yielded similar relationships as initially described by Cheong et al., [5] reproduced in panel B (n = 857). Permission to reproduce the figure in panel B was granted by the publisher (Wolters Kluwer Health).

Figure 2

Ejection fraction (EF) measured by contemporaneous echocardiography and cardiovascular magnetic resonance (CMR) correlate only moderately (panel A), and there is considerable scatter and misclassification. Bland-Altman analysis (panel B) reveals that this scatter does not result from systematic bias. Importantly, most of scatter occurs in the 30%-50% range of the EF spectrum where clinical decision making relies most heavily on EF measures as shown by the thin gray box in panel B. Of note, variation far exceeded the ∆ 5% increment used for EF reporting by echocardiography. In Panel C, despite similar median EF values and the absence of meaningful bias in the EF measures of the population, the scatter exhibited by the individual differences in echocardiography and CMR EF measures culminate in 102 individuals (23%) of the sample being categorized differently (highlighted in bold font).

Figure 3

Graphical depiction of the Net Reclassification Improvement (NRI) where univariable Cox regression models with cardiovascular magnetic resonance (CMR) ejection fraction (EF) predicting all cause mortality (panel A) or death or cardiac transplant (panel B) are compared to Cox regression models containing echocardiography (echo) EF. Since the reclassification improved using CMR EF relative to echocardiography EF in both those with events and those without events, the NRI for all cause mortality and death/cardiac transplant are 0.51 (includes rounding error; panel A) and 0.61 (panel B), respectively, after summing these net improvements for events and nonevents.

Figure 4

Adjusted Kaplan Meier survival curves for all cause mortality (panel A) and death or cardiac transplantation (panel B) according to late gadolinium enhancement (LGE) accounting for variation in age, ejection fraction by echocardiography, and regional wall motion abnormalities detected by echocardiography.