Deceleration time and E/A show strongest association with declining estrogen levels as parameters for HFpEF definition in post-menopausal women

Background: Menopause is linked to an elevated risk of heart failure with preserved ejection fraction (HFpEF). However, HFpEF definition in clinical routine is challenging as a multitude of echocardiographic parameters are included in the ESC consensus criteria and in scoring systems along with fundamental diastolic dysfunction analysis. In relation to menopause, estrogen decline was shown to be an important driver for cardiovascular disease progression. However. it is not known which of the relevant HFpEF parameters depend most on estrogen levels. This is of great importance, as it would simplify clinical screening for menopause women for early diagnosis of developing HFpEF.  

Methods: In this mono-centre pilot study. 141 women with precise echocardiographic assessment including strain analysis were included. Parameters for HFpEF definition were assessed [E/e’ mean, lateral and septal e’, right wall thickness (RWT), global longitudinal strain (GLS), E/A quotient, deceleration time (DT), left atrial volume index (LAVI), left ventricular mass index (LVMI), peak tricuspid regurgitant velocity (TRV)]. Whole blood was taken, and plasma was generated by centrifugation. Oestrogen concentration as well as progesterone levels were detected in plasma by ELISA (ab108667. ab108670).

Results: Mean age of women included in the study was 74 years. Of the total sample, 124 were postmenopausal, four had initiated the menopausal transition at the time of inclusion in the study, and 13 were premenopausal. A total of 31 (22%) participants had a body mass index (BMI) greater than 30, while 44 (31.2%) had been diagnosed with type 2 diabetes mellitus. Out of all included parameters, deceleration time and the E/A quotient only were identified to be associated with estrogen levels (DT <220 ms: 25.13 pg/ml ± 14.73 vs. DT >200 ms: 18.90 pg/ml ± 11.22. p = 0.0441; E/A >0.8: 24.93 pg/ml ± 15.65 vs. E/A <0.8: 17.49 pg/ml ± 9.59. p = 0.0392). Correlation of DT>220ms and estrogen concentrations showed a positive correlation (r=0.4274. p=0.0066). Interestingly. progesterone did not show any relevant association (DT <220 ms: 0.7127 ng/ml ± 0.4646 vs. DT >200 ms: 0.6079 ng/ml ± 0.4121. p = 0.3245; E/A >0.8: 0.6906 ng/ml ± 0.4763 vs. E/A <0.8: 0.5202 ng/ml ± 0.4167. p = 0.1655; E/e’ – n.s.; lateral e’ – n.s.; septal e’ – n.s.; RWT – n.s.; GLS – n.s.; LAVI – n.s.; LVMI – n.s.; TRV – n.s.).

Conclusion: In this study. we could demonstrate that E/A and deceleration time appear to respond most significantly to declining estrogen levels. In contrast, progesterone concentration did not show any difference indicating highest relevance for estrogen as underlying hormone in hormone transition. Results of this analysis help to simplify screening algorithms for early HFpEF detection in menopause women.