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- Posted Monday November 30, 2015
TGen and Barrow Neurological Institute identify genes linked to stress-triggered heart disease
Researchers identify a series of rare genetic changes, showing which patients might be at risk for 'broken heart syndrome'
PHOENIX, Ariz. - Nov. 30, 2015 - Researchers at
theTranslational Genomics Research Institute (TGen)
and Barrow Neurological Institute have for the first time
identified genetic risk factors that are linked to stress-induced
cardiomyopathy (SIC), a rare type of heart disease.
Patients with SIC generally show no symptoms until they suffer
some form of intense emotional or physiological distress. For this
reason the disorder is sometimes referred to as "broken heart
syndrome," and because of its unusual presentation has captured the
attention of physicians for centuries.
In a study published Nov. 24 in the journal Neurosurgery,
researchers report on the identification of new genetic risk
factors through the use of the powerful approach of genomic
sequencing. Knowing which patients harbor the genes associated with
SIC could help guide their care and treatment before, and after,
they suffer a life-threatening stressor that induces SIC.
Using ultra-high resolution cameras and supercomputers,
researchers identified the suspect genes by next generation DNA
sequencing, essentially by spelling out the billions of bits of
information in the genomes of seven women who exhibited SIC
following a brain aneurysm.
"We hypothesize that patients at highest risk for SIC likely live
in a compensated state of cardiac dysfunction that manifests
clinically only after the heart muscle is stressed," said Matt
Huentelman, Ph.D., Associate Professor of TGen's Neurogenomics
Division, and the senior author of the study. "We have identified a
series of rare genetic changes associated with this disease that
may be used for early identification of patients at risk."
Patients who volunteered for the study were among the 21 victims
of hemorrhagic stroke treated at Barrow between 2005-13, and who
were diagnosed with SIC. None of the patients had significant prior
cardiac history. Barrow is a leading neurotrama center with more
than 300 hemorrhagic stroke patients each year.
"We propose that SIC is an example of a hidden heart disease with
a distinct physiological trigger, and suggest that alternative
clinical approaches to these patients may be warranted," said
Yashar Kalani, M.D. and Ph.D., a chief resident in Neurological
Surgery, assistant professor at Barrow at Dignity Health St.
Joseph's Hospital and Medical Center, and the study's lead
author.
Among the gene variants identified in the study as associated with
SIC are MYLK2, DSG2, FKTN, and LDB3. Importantly, all of these
genes were previously known to play a role in other cardiac
diseases, but not in SIC.
All of these variants are extremely rare. Among the 65,000
publicly available human genomes, MYLK2 had previous been seen in
only 1,539 individuals (1.3 percent), DSG2 in 224 (0.1 percent),
FKTN in just 3 (0.002 percent), and LDB3 had never before been
sequenced.
SIC, also known as or Takotsubo cardiomyopathy, is a poorly
understood, and likely under-diagnosed, phenomenon.
"Clinically, SIC is challenging to treat in the critically ill
patient, in part because the treatment may exacerbate the
sickness," Dr. Kalani said. "A blood-based biomarker for SIC has
been elusive until recently and could greatly aid with early
identification of patients at risk."
In some cases, the very drug used to treat a heart attack could
worsen the condition of patients with SIC.
"Identification of patients at risk for SIC, based on genetic
predispositions, would allow for tailored treatment upon admission
of these patients to the intensive care unit, and perhaps prior to
a decline of the heart and brain," said Dr. Huentelman. "The panel
of genes identified by our analysis provides a means of identifying
patients who may be at risk for developing this type of heart
disorder, and may also be useful in helping those at the highest
risk avoid SIC altogether."
The study - Rare Variants in Cardiomyopathy Genes Associated
with Stress-induced Cardiomyopathy - was published online Nov.
24 in Neurosurgery, the official journal of the Congress
of Neurological Surgeons. Read the abstract at: http://www.ncbi.nlm.nih.gov/pubmed/26606670.
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About Barrow Neurological Institute:
Barrow Neurological Institute at Dignity Health St. Joseph's
Hospital and Medical Center inPhoenixis internationally
recognized as a leader in neurosurgery, neurology, neurological
research and patient care. Consistently voted among the top
facilities in the United States for neurological care, Barrow
treats patients with a wide range of neurological conditions,
including brain and spinal tumors, cerebrovascular conditions,
concussions and neuromuscular disorders. Its surgeons perform more
neurosurgeries annually than any hospital in the nation. Barrow is
proud to be home of the Muhammad Ali Parkinson Center. St. Joseph's
is a member of Dignity Health, one of the nation's largest health
care systems. For more information, please visit thebarrow.org.
Press Contact:
Carmelle Malkovich
Media Relations Manager
602-406-3319
[email protected]
About TGen
Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with neurological disorders, cancer, and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit). TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and
effectiveness of the translational process. For more information,
visit:www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]