Sex differences in myocardial oxygenation and energetics in patients with severe aortic stenosis without obstructive coronary artery disease before and after aortic valve replacement (RF_TH_216)

Biological sex impacts myocardial remodeling and clinical outcomes in aortic stenosis (AS). Phosphorus magnetic resonance spectroscopy (³¹P-MRS) non-invasively assesses myocardial phosphocreatine to ATP concentration ratio (PCr/ATP): a sensitive indicator of myocardial energetic status. Blood-oxygen level-dependent (BOLD) cardiovascular magnetic resonance (CMR) non-invasively assesses myocardial tissue oxygenation without exogenous contrast by measuring BOLD signal intensity (SI) differences, reflecting deoxygenated hemoglobin concentration during adenosine stress.
The objective of this study was to determine sex differences in myocardial oxygenation (measured by BOLD signal intensity change between rest and adenosine stress BOLD CMR [BOLDΔSI]), and energetics (measured by PCr/ATP ratio) in severe AS without obstructive coronary artery disease (CAD) before aortic valve replacement (AVR) and recovery post-AVR.

Methods:

This was a prospective single-center longitudinal cohort study (recruiting from April-2019 to November-2023), in a tertiary cardiovascular center. Patients with severe AS (n=202) undergoing AVR were recruited, alongside healthy controls (n=39). Participants underwent cardiovascular magnetic resonance (CMR) 1-month prior (n=202) and 6-months post AVR (n=162). Significant obstructive CAD was excluded in AS patients by coronary angiography.




Results: Patients were matched in age, AS severity and comorbidities. Pre AVR, both myocardial oxygenation and energetics indexes were significantly lower in female and male patients with severe AS compared to sex-matched healthy controls. However, there were no significant differences in BOLDΔSI (8.5[5.4,13.3] vs 6.9[2.8,12.1];P=0.063), or PCr/ATP ratio (1.72[1.48,1.87] vs 1.67[1.37,1.89];P=0.46) between female and male patients with AS (Figure 2).
Significant improvements inBOLDΔSI were seen post AVR both in females (from 8.5[5.4,13.3] to 13.4[9.2,20.0];P=0.0013) and males (from 6.9[2.8,12.1] to 10.6[5.7,16.2];P=0.0003). Improvements in PCr/ATP were also shown in both females (from: 1.72[1.48,1.87] to 2.10[1.76,2.30]%;P=0.0005) and males (from 1.67[1.37,1.89] to 1.84[1.65,2.05]%;P=0.0026). Post-AVR measurements for PCr/ATP were significantly higher in the female AS group compared to the male AS group.
In male AS patients, despite significant post AVR improvements, compared to sex matched controls bothBOLDΔSI (10.6[5.7,16.2] vs 16.1[10.8, 27.5]%,P=0.030) and PCr/ATP (1.84[1.65,2.05] vs 2.10[1.83,2.56];P=0.014) remained impaired. In the female group, the PCr/ATP ratio was no longer impaired compared to controls (2.10[1.76,2.30] vs 1.98[1.79,2.33],P=0.92). However similar to males the BOLDΔSI remained significantly impaired compared to female controls (13.4[9.2,20.0] vs 21.2[17.9,24.6]%;P=0.0020).

Pre- and post AVR, there was no significant differences in LV systolic function between female and males patients with AS, or compared to sex matched controls. Global longitudinal shortening (GLS) was significantly lower in females and males with AS pre AVR compared to controls, remaining significantly impaired post AVR despite improvements in both sexes. GLS correlated with BOLDΔSI value (r=0.27, p=< 0.0001).

Conclusion:

In patients with severe AS without obstructive CAD, biological sex does not significantly impact myocardial energetics or oxygenation pre or post-AVR with significant improvements in energetics and oxygenation detected in both sexes post-AVR.