By Miles Henderson
– Women have been playing catch-up in medical treatment for a long time. 50 years ago, radical mastectomies were the gold standard for women’s oncology, a taxing and unnecessary procedure in which the cancerous breast was removed, alongside the overlying skin and much of the muscle tissue beneath. Today, a new medical consensus provides several appropriate options for treating breast cancer that are tailored to women – taking into account factors such as hormonal differences.
Just beneath the breast, new research coming out of the VU University Medical Center (VUmc) points to the little-known heart disease hypertrophic cardiomyopathy (HCM) as another condition lacking a careful sex-specific approach. In a paper that details this novel exploration of sex-differences in HCM, the VUmc researchers outline a potential cause for what their data revealed: women are diagnosed at a much older age and have worse chances of survival than men.
Some of AUC’s biomedical students may have been introduced to HCM in class, yet few people outside the sciences will have heard of it. Despite its lack of notoriety, the condition can be devastatingly lethal and is the most common genetic heart disease. Dr. Jolanda van der Velden, AUC Professor, Department Chair at the VUmc, and co-author of the paper, explains that it can be the cause of sudden heart failure: when people die of cardiac arrest abruptly without warning, it’s usually HCM. She recalls that 10 years ago a cardiologist told her “not to be bothered” by such a rare disease. Since then, improvements in genetics estimate that the HCM mutation is present in around 1 out of every 200 people.
Compounding the newly understood severity of the disease is the recently found discrepancy in age and survival rates between the sexes. Why are women affected so differently?
Dr. Beau van Driel, a researcher working on HCM at the VUmc and co-author of the paper, outlines one possible explanation: clinical bias, a phenomenon where strange results are found in patient distribution because referrals given by doctors to studies differ from cases of HCM in the general population. He adds that there might be a gender bias component to this. To take one hypothetical, doctors might treat symptomatic complaints differently when they come from women.
A more likely explanation, according to the paper coming out of the VUmc, is tied to the official criteria used to diagnose HCM. The paper explains that HCM is diagnosed by looking at the thickness of the heart muscle. Currently, the official width used is 15 millimeters. Dr. van der Velden says this number is a big problem. “As a basic scientist that always appeared very strange to me, because whenever we do studies in mice, we have to correct for body surface area,” she says. “But for humans, the diagnostic criterion is the same for women and men, who tend to be quite different in size.”
Correcting for body surface area is a common practice in the diagnosis of other cardiovascular diseases, yet it is curiously absent from HCM diagnosis. Women have hearts about two thirds the size of men’s, so it makes sense that women with HCM could have a greater relative thickening of the heart before they are officially diagnosed. This means that the condition may be identified later in women, and as a result, women with HCM could be missing out on early treatment.
So, how can this newly identified problem be addressed? Dr. van Driel says that their first priority is to bring scientific attention to the issue. He also calls for additional research to resolve, definitively, whether the diagnostic criterion is in fact the true cause of sex-differences seen in HCM. As this discovery is a first, efforts are being made to continue the research established by Dr. van der Velden and Dr. van Driel. Seeing as HCM is relatively new for researchers, with current understanding of the disease being a culmination of the last fifteen years of research, a full grasp of HCM may require “another fifteen years,” says Dr. van Driel.
Additionally, within AUC’s Human Body course, Dr. van der Velden highlights HCM as a means to explain features of the cardiovascular system. She states the importance of integrating these insights when teaching new students, who will have the opportunity to follow current gaps in research, and may be inspired to tackle them later on.
Currently, the European Society of Cardiology maintains their 2014 revision to HCM guidelines, which is defined by a minimum wall thickness that is universal and sex-blind. This is unlikely to change unless concrete evidence wags its finger at the diagnostic criterion.
For students interested in reading the paper by Dr. van der Velden and Dr. van Driel, it can be found in the journal Current Opinion in Cardiology.
Illustration by Miles Henderson