The article focuses on the motivation for and the impact of HCM genetic testing on family members. The 32 participants in the study all encouraged family members to undergo genetic testing with the hope that the knowledge gained would benefit family members down the line. However, the study found that the psychological impact of a positive result, in the absence of overt disease, was highly variable. Some gene positive individuals perceived that they had an absolute risk of developing HCM, with substantial detriment to their lifestyle choices, while others were not at all affected by the result and made no lifestyle changes.
Researchers in Norway have demonstrated that patients who carry a HCM gene show reduced cardiac volume when compared to healthy individuals. Patients with overt HCM show even further reduction to their cardiac volume than those who merely carry the gene.
Although the gene positive individuals lacked the characteristic left ventricular wall thickening of HCM, diastolic and systolic volumes were reduced when compared to healthy individuals. Hence, the researchers concluded that a person who is gene positive for the disease may show reduced volume before developing hypertrophy.
The study included 180 patients with left ventricular hypertrophy, 100 patients who carried the HCM gene but did not show signs of left ventricular hypertrophy, and 80 healthy individuals.
The researchers theorize that early changes in HCM result from the gradual stiffening of the left ventricle, which contributes to filling changes before anatomical thickening is apparent. These changes will likely worsen as the disease progresses.
The researchers suggest future long term studies of gene positive individuals with small cardiac volume who show signs of diastolic and systolic dysfunction. These patients, they suggest, are the most likely to go on to develop HCM.
A study published this week by HCM researchers in Canada found that double mutations in patients with hypertrophic cardiomyopathy are much less common than previously thought. In particular, researchers found that except for those with double mutations in the gene MYBPC3, there is not much data to support the finding that there is a worse clinical course for those patients who have double HCM mutations.
Hence, in the absence of extraordinary circumstances, such as two MYBPC3 mutations, the researchers caution that double mutations should not be the sole justification for the insertion of an implantable defibrillator.
The study looked at patients >18 years of age who underwent genetic testing at the Toronto General Hospital between January 2005 and June 2016. Out of a sample of 1411 patients, 9% of those who were gene-positive patients had 2 genes, but only in 1 case (0.4%) were both genes classified as those known to cause HCM.
In addition to looking at their own patients, the researchers also re-examined data from previously published studies. Similarly, they found when they re-analyzed the data that only 0.4% of the 8% of patients previously found to have double mutations in fact carried multiple pathogenic mutations.
When a patient is the only person in the family ever diagnosed with HCM, s/he will often wonder whether their disease is, in fact, genetic. S/he will also wonder whether it will be necessary for all first degree relatives to undergo serial screenings for the rest of their lives.
In answer to this concern, Australian researchers have recently identified a subset of HCM patients who appear to have a non-familial form of the disease and whose relatives may be candidates for less stringent screening protocols.
The study, just published in Circulation: Cardiovascular Genetics by Dr. Jodie Ingles and Dr. Chris Semsarian, found that this group, having neither genetic mutation associated with HCM nor family history of HCM, comprises approximately 40% of all HCM patients. Non-familial HCM patients are more likely to be older when diagnosed, and they often present with non-asymmetric hypertrophy and hypertension. And, these HCM patients appear to have a more favorable clinical course, with a better track record of survival from major cardiovascular events.
The researchers point out that by sorting patients into more distinct subgroups, doctors will be able to provide more personalized and evidence-based care to patients and their families. In particular, their recommendation is that first-degree relatives of non-familial HCM patients need only be screened one or more times in adulthood. Less frequent follow up surveillance is also suggested, in contrast with the more intensive screening guidelines recommended for family members of patients with familial HCM.
The same study also found that gene positive children without overt signs of the disease are at relatively low risk for cardiac events.
The study included 119 children, positive for at least one HCM gene, with a median age of 12.1 years. 8 of these children (6.7%) received a HCM diagnosis within the time span of the study [which varied from 3.1 to 10.7 years]. 1 of the 8 diagnosed children suffered a cardiac event which necessitated implantation of an implantable cardioverter defibrillator or ICD.
The study did caution, however, that because severe hypertrophy and cardiac events may develop, it is important to refine risk stratification and long term follow up procedures for gene positive kids.
A study published today by Dr. Carolyn Ho, of Boston’s Brigham and Women’s Hospital, and colleagues, including Australia’s Christopher Semsarian, found that there are several factors which appear to stand out in young people who later go on to develop HCM.
The children/adolescents/young adults who participated in the study all carried at least one gene associated with HCM, and were members of families with strong histories of HCM. None of the 38 young people had clinical manifestations of HCM at the beginning of the study period, while 4 went on to develop HCM by the end of the study. In collecting the data analyzed in the study, the test results of the 4 individuals with HCM were compared to the 34 individuals that did not have HCM at the end of the study.
The factors associated with the development of overt HCM, as identified by the researchers, were: abnormal left ventricular relaxation and higher ejection fraction, EKG changes, longer mitral valve leaflets, higher NT-proBNP concentrations and troponin values.
In the conclusion, the authors acknowledged the need for further research and investigation in order to better understand the natural course and evolution of the disease.
A recent study published in The New England Journal of Medicine concluded that individuals of African descent found to carry genes previously identified with HCM did not, in fact, have the disease. Thus, the article highlighted the importance of including diverse populations when sequencing genomes for genetic diseases so as to avoid false diagnoses.
The New York Times also picked up this story, focusing its article on the negative repercussions that can result from a false positive genetic test for HCM.
In connection with the findings, National Public Radio interviewed three people, including Dr. Isaac Kohane, one of the researchers who published the findings of the lack of diversity in the HCM genetic panel, as well as New York City HCM patient Tarika Mingo. Finally, NPR spoke to veteran HCM expert Dr. Barry Maron, who noted a potential concern that athletes may have been erroneously disqualified from sports participation solely on the basis of false positive genetic testing results.
A recent study followed 14 patients carrying one of two known genes associated with HCM (MYBPC3 and MYH7) over a 10+ year period . At the time of gene identification, none of the patients shown clinical evidence of hypertrophy. Over the time span of the study, 3 patients, who were then adults, had developed signs of HCM. Hence, the study suggests that periodic screenings are necessary for gene positive individuals throughout adulthood.
According to Cardiomyopathy U.K., the researchers undertook this project due to the lack of information and guidelines available to patients who are gene positive but have no outward signs of the disease.