Association of Feature-Tracking Cardiac Magnetic Resonance Imaging Left Ventricular Global Longitudinal Strain with All Cause Mortality in Patients with Reduced Left Ventricular Ejection Fraction

Direct assessment of myocardial fiber deformation with echocardiographic global longitudinal strain (GLS) has shown promise in providing prognostic information that is incremental to ejection fraction (EF) in patients with left ventricular dysfunction¹.

Cardiac Magnetic Resonance (CMR) imaging has now evolved into a major tool for evaluation of patients with left ventricular dysfunction, providing precise measurements of EF, and viability assessment with late gadolinium enhancement (LGE). Recent development of CMR feature-tracking techniques now allow assessment of GLS from standard cine CMR images without the need for specialized pulse sequences or additional scanning time². We therefore hypothesized that CMR feature-tracking derived GLS may provide incremental prognostic information in these patients.

Consecutive patients (n=470) undergoing CMR with both cine and LGE imaging for evaluation of ischemic or nonischemic dilated cardiomyopathy with EF<50% were included in this retrospective study. Comprehensive phenotyping including clinical history, imaging, and cardiac catheterization classified 330 individuals with ischemic and 140 with non-ischemic cardiomyopathy. Institutional review board approval was obtained. Steady state free precession cine images were acquired in multiple short-axis and three long-axis views. LGE imaging was performed 10–15 minutes after Gadolinium contrast (0.15mmol/kg) administration using a 2D-segmented gradient echo inversion recovery sequence in the same views used for cine CMR. The size of LGE (as a percentage of total left ventricular myocardium) was determined as previously described³. Endocardial left ventricular contours were manually traced (by a single physician who was blinded to patient information and outcomes) in all 3 long-axis cine views to derive GLS using the Qstrain feature-tracking package (Medis Medical Imaging Systems, Leiden, the Netherlands). Patients were followed for the primary outcome of all-cause mortality using the United States Social Security Death Index. Time to event was calculated as the period between the CMR study and death. Patients who did not experience the primary outcome were censored at the time of assessment. Analyses were performed using STATA (StataCorp, TX).

The mean age of the study population was 60±15years. Sixty-nine percent were male and 30% had diabetes. The mean EF was 34.2±9.8%. Mean GLS was −10.4±4.6%. Median GLS was −10.3% (interquartile range: −7.1 to −13.6%). During a median follow-up of 4.1years (interquartile range: 3.5–4.8 years), 93(19.8%) patients died.

By Kaplan-Meier analysis, the risk of death increased significantly with worsening tertiles of GLS (log-rank p<0.0001) (Figure 1A) as well as with increasing tertiles of LGE size (log-rank p=0.01) (Figure 1B). LGE size demonstrated a significant univariable association with death (HR=1.03 per %; 95%CI 1.01–1.05; p<0.001). Likewise, EF demonstrated a significant univariable association with death (HR=0.97 per %; 95%CI 0.95–0.99; p=0.006).

Figure. Survival analysis.

A, Kaplan-Meier curves for survival, stratified by tertiles of GLS (Chi²=85.16). B, Kaplan-Meier curves for survival, stratified by tertiles of LGE size (Chi²=8.01).

After adjustment for clinical and imaging characteristics (age, body mass index, diabetes, hypertension, etiology of cardiomyopathy, left ventricular end diastolic volume index, LGE size, EF), which had univariable associations with death (at p≤0.20), GLS remained significantly associated with death (HR=2.35 per %; 95% CI 1.81–3.06; p<0.001). In this model, EF remained significantly associated with death (HR=0.95 per %; 95% CI 0.91–0.99; p=0.038) but LGE size was not (HR=1.02 per %; 95% CI 0.99–1.04; p=0.186). Addition of GLS in this model resulted in significant improvement in the global chi square (31 to 157; p<0.0001) and C-statistic (0.64 to 0.85; p<0.0001). Continuous net reclassification improvement (NRI) was 1.16 (95%CI, 0.95–1.38), with an integrated discrimination improvement (IDI) of 0.32 (95%CI, 0.22–0.40).

This study shows that GLS measured by feature-tracking CMR demonstrates a strong, independent association with mortality in ischemic and nonischemic dilated cardiomyopathy; providing prognostic information incremental to common clinical and CMR imaging risk factors, including EF and LGE. The reasons for this are not clear, but may relate to the subendocardial location of the more longitudinal myocardial fibers which seem to be exquisitely sensitive to disturbance by various pathologies. This is the largest study suggesting use of feature-tracking CMR for prognostic assessment; and the first study to include patients with ischemic cardiomyopathy. These findings may have significant implications for management decisions based on risk stratification of these individuals.

Prior studies have shown the prognostic value of GLS, derived using speckle-tracking echocardiography¹. However, speckle-tracking techniques are highly dependent on attainment of good quality imaging and suboptimal acoustic windows can result in poor results or time consuming analysis requiring significant operator experience. CMR feature-tracking provides an alternative means to obtain GLS in these patients albeit with some limitations in those with implanted devices, arrhythmias and claustrophobia. Prior data regarding CMR feature-tracking GLS and prognosis has been limited to a single small study of 210 dilated cardiomyopathy patients with only 10 deaths ⁴. Our study extends these observations to patients with ischemic cardiomyopathy - with a significantly greater number of hard events.

Follow-up data in this study was limited to all-cause death. However, many have argued that all–cause mortality is an extremely important and appropriate study endpoint because it is objective, clinically relevant and unbiased, which is often not the case for cardiac mortality or softer outcomes such as revascularization or hospitalization⁵. Data regarding non-cardiac comorbidities, subsequent defibrillator/resynchronization therapy or revascularization was not available.

Future studies are warranted to explore the role of CMR feature-tracking derived GLS in clinical decision making for these patients.