Sex differences in coronary care and outcome in patients with a normal perfusion CMR

Background: The number of normal coronary angiographies in patients presenting with symptoms suggestive of chronic coronary syndrome (CCS) remains high, especially in females¹. Cardiac magnetic resonance imaging (CMR) with stress/rest perfusion has shown the potential for accurate identification of CCS patients in need of coronary intervention. The aim of this study was to investigate sex differences in outcome and number of normal angiographies performed, in patients with normal findings on stress/rest perfusion CMR.

Methods: Patients from the CMR arm of the multi-modality CHOICE registry (n=2239) were eligible for inclusion. All patients were referred for a stress/rest perfusion CMR mapping using a dual-sequence, single-bolus technique² at Skane University Hospital in Lund, Sweden, between 2019-2022. Of these, only patients with normal CMR findings defined as no signs of stress-induced ischemia and no infarction by late gadolinium enhancement were included in the current sub-study. Follow-up data was obtained from the Swedish National Board of Health and Welfare Registry and MACE (major adverse cardiovascular events) was defined as cardiovascular death, myocardial infarction, unstable angina and coronary intervention (PCI or CABG). In addition, the number of invasive angiographies and the proportion without subsequent coronary intervention was determined and stratified by sex.

Results: A total of 1500 patients (764, 51% females) had normal perfusion CMR findings (Table 1). The females were older (65±13 vs 62±13 years, p >0.001) and had lower prevalence of ischemic heart disease (9% vs 13%, p=0.01) than males. The overall risk of MACE was low (4.6%), with more MACE in males compared to females (22 vs 47, p=0.002, Figure 1). A total of 126 patients (8.4%) underwent invasive angiography during the follow-up. Of these patients, a higher proportion of females (68%) had no subsequent revascularization procedure performed compared to males (42%, p=0.004) as shown in Figure 2.

Conclusion: Patients with no stress-induced ischemia and no infarction on CMR have a good prognosis, with a low risk of MACE, especially in females. The frequency of unnecessary angiographies is, however, higher in females in this patient group.

Table 1. Patient characteristics and events (n=1500).

	Females (n=764)	Males (n=736)	P-value
Age (years±SD)	65±13	62±13	< 0.001
Diabetes	56 (7%)	62 (8%)	0.43
Hypertension	185 (24%)	189 (26%)	0.51
Prior ischemic heart disease	66 (9%)	94 (13%)	0.01
Follow-up data:
Follow-up time (years±SD)	2.7±0.8	2.6±0.9	0.01
MACE	22 (3%)	47 (6%)	0.002
Invasive angiography	47 (6%)	79 (11%)	0.002

Figure 1. Sex-distribution of MACE during 5-year follow-up in patients with a normal perfusion CMR examination.
Figure 2. Proportion of patients without subsequent revascularization (PCI or CABG) following invasive coronary angiography during the 5-year follow-up. Note that the proportion of females (68%) was significantly higher than in males (42%).