Sex Differences in Advanced Cardiac MRI Assessment

See also the article by Rutkowski et al in this issue.

Karen Ordovas, MD, MAS, is a professor in residence, director of cardiac imaging in the department of radiology and biomedical imaging at the University of California, San Francisco. She specializes in cardiac and pulmonary imaging, in particular cardiovascular CT and MRI at the UCSF Imaging Center. She received her medical degree from Universidade Federal do Rio Grande do Sul, Brazil, and completed her residency in radiology at the Instituto de Cardiologia do Rio Grande do Sul, Brazil. She has completed research and clinical fellowships in cardiothoracic radiology at UCSF and earned a master’s degree in clinical research from the department of epidemiology and biostatistics at UCSF. Dr Ordova’s research interests include establishing evidence-based applications for coronary CT angiography and cardiac MRI in several clinical settings. Her articles have appeared in Radiology, American Journal of Cardiology, JACC: Cardiovascular Imaging, and Stroke: A Journal of Cerebral Circulation.

It is of ultimate importance that physicians understand sex and gender differences in cardiovascular disease presentation and response to interventions (1). More specifically, the classic medical knowledge of cardiovascular diseases derives primarily from experimental models and clinical studies with underrepresentation of female subjects (2). Awareness of the historical gender-biased approach to cardiovascular disease has led to many initiatives from professional societies and funding agencies to ensure sex differences are captured in basic and clinical research in the field (3).

Following this new norm in biomedical research, the current study by Rutkowski et al (4) investigates sex differences in cardiac imaging parameters obtained from advanced cardiac MRI technology for in vivo assessment of cardiac efficiency and flow dynamics: four-dimensional (4D) flow MRI. The investigators present the first study comparing kinetic energy as measured by using 4D flow cardiac MRI between healthy male and female volunteers and show that there is significant difference in left ventricular vorticity between male and female subjects. The study findings introduce the concept that there are cardiac efficiency discrepancies between sexes that can be measured by advanced cardiac MRI and should be taken into account when assessing cardiac health.

The field of 4D cardiac MRI has developed significantly in the past few years. Most studies have focused on comparison of 4D flow–derived cardiac MRI parameters between healthy volunteers and a small sample of patients with known cardiovascular disease (5–7). In addition, some groups have proposed normal ranges for 4D flow parameters, with particular emphases in differences between age groups (8,9). Very few previous publications have highlighted sex or gender differences in 4D flow parameters. Föll et al have documented sex-related differences in ventricular flow vorticity which were not explained by ventricular geometric differences (10). Garcia et al have shown that peak flow velocity of the aorta measured by 4D flow was significantly different between male and female sexes, even when controlling for heart rate (11).

When looking at different advanced cardiac MRI techniques such as multiparametric imaging, several investigators have documented sex differences in T1, T2, T2*, and extracellular volume (ECV) parameters in healthy volunteers. Roy et al have shown that mean myocardial T1 and ECV at 3 T were significantly greater in age-matched women than in men, whereas T2 and T2* values were not different between the sexes (12). Similarly, Liu et al have analyzed data from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort and showed that women had significantly greater ECV and native T1 compared to men, as well as lower postcontrast T1 values (all P < .05) (13). However, there are no large data sets to date to determine sex-specific normal ranges for these parameters.

In the clinical arena, sex-specific standards of reference for cardiac MRI parameters are available, including cardiac volumes, function, and mass (14,15). More recently, the European Association of Cardiovascular Imaging has published an expert consensus on classification of cardiac MRI abnormal values into mild, moderate, and severe ranges, including sex-specific recommendations (16). In addition, cardiology guidelines for imaging diagnosis and disease management include some sex-specific recommendations, such as on cardiac MRI diagnosis of arrhythmogenic right ventricular cardiomyopathy (17) and adults with congenital heart diseases (18).

In summary, the work by Rutkowski et al is a small hypothesis-generating study applying advanced cardiac MRI to better understand sex difference in cardiac efficiency. However, the data presented in this article can be extremely useful to guide future study designs and to inform important research questions for subsequent clinical studies in the field.