Increased circumferential deformation predicts cardiac events when left ventricular ejection fraction is normal
Authors: Skaarup K G , Lassen M C H , Johansen N D , Olsen F J , Jensen G B , Schnohr P , Shah A , Claggett B L , Solomon S D , Mogelvang R , Biering-Sorensen T 
Published: October 2022

Abstract

Background
Recent research suggests that early left ventricular (LV) systolic dysfunction is characterized by compromised longitudinal function and a concomitant augmentation of circumferential deformation expressed as increased global circumferential strain (GCS). It is hypothesized that increased GCS could be used to identify people at higher risk of cardiovascular events when left ventricular ejection fraction (LVEF) is preserved.

Purpose
The present study aimed to investigate whether elevated GCS in individuals with preserved LVEF predicts major adverse cardiovascular events (MACE).

Methods
A total of 2,874 participants from the general population were included in this prospective cohort study. All participants had echocardiography performed and analyzed. Exclusion criteria were HF at baseline, non-sinus rhythm during echocardiography, and inadequate image quality for GCS assessment. Outcome was MACE including incident heart failure, myocardial infarction, and/or cardiovascular death. Absolute values of strain were used. To determine the optimal transition point of a potential effect modification, Cox regression models with different LVEF thresholds were created. The model with the optimal hazard ratio (HR) and P values of the interaction terms and Akaike information criterion was chosen.

Results
Mean age was 53±18 years and 60% were female. Mean LVEF and GCS were 57±6% and 21.6±4.0%, respectively. Median follow-up was 3.5 years [IQR: 2.6; 4.4] and a total of 92 (3.2%) developed MACE. A U-shaped relationship was observed between GCS and MACE. The lowest incidence rate was within the GCS range of 20 to 25% (Figure 1a). A significant interaction (P&lt;0.001) between GCS and LVEF was observed regarding MACE. The optimal transition point for this effect modification was determined to be LVEF=50%. In multivariable Cox regressions (including conventional cardiovascular risk factors and global longitudinal strain (GLS)), increasing GCS was significantly associated with future MACE in participants with LVEF ≥50% (HR=1.09 [95% CI: 1.01; 1.17] per 1% increase, n=2420) while decreasing GCS were associated with a higher risk of MACE in individuals with abnormal LVEF (HR=1.16 [95% CI: 1.04; 1.29] per 1% decrease, n=289) (Figure 1b). A total of 50 (2.1%) developed the MACE amongst the participants with LVEF ≥50%. This group had significantly lower GLS (19.0±2.7% vs 19.9±2.0%, P=0.013) and ratio of peak early transmitral filling velocity to peak early diastolic tissue velocity (E/e') (10.7 [IQR: 7.9; 14.3] vs 6.5 [5.3; 8.4], P&lt;0.001) compared to the participants that did not develop MACE with normal LVEF. Figure 2 illustrates a model of the development of GCS, LVEF, GLS, and E/e' as LV function declines.

Conclusion
In the general population, the prognostic value of GCS is modified by LVEF. In participants with normal LVEF, higher GCS was associated with increased risk of MACE, while the opposite was observed in participants with abnormal LVEF.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Copenhagen City Heart Study is funded by The Danish Heart FoundationThe Metropolitan Region of Denmark (public funding).