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Role of Diagnostics in Personalized Management
of Cardiovascular Disease
Cardiovascular Disorders with a Genetic Component
Several cardiovascular diseases are recognized to have a genetic component; indeed,
a family history of heart disease has always attracted the physician’s attention. In
recent years, molecular genetics has contributed to the development of molecular
cardiology, opening up some new pathways to the diagnosis, prevention, and treat-
ment of some cardiovascular diseases. Genetic approaches have succeeded in defi n-
ing the molecular basis of an increasing array of heart diseases, such as hypertrophic
cardiomyopathy and the long-QT syndrome (Brugada Syndrome), a potentially
fatal cardiac disorder associated with serious arrhythmias. Some of the genes that
cause cardiovascular diseases are shown in Table 14.2.
Long Q-T syndrome is an inherited form of ventricular arrhythmia in which the
interval between the Q and the T waves is longer than normal. This disease refl ects
a defect in the electrical properties of the cardiac muscle, which predisposes the
patient to life-threatening ventricular fi brillation after stress. Five genes have been
identifi ed where the mutations are associated with this disorder. These genes encode
cardiac potassium ion channels and support the hypothesis that the LQT syndrome
results from delayed myocellular repolarization. The diagnosis of long QT syn-
drome and other channelopathies by an electrocardiogram is often diffi cult and may
be missed, which leaves a patient at risk for sudden cardiac death. FAMILION™
(Transgenomic) is the fi rst commercially available, comprehensive genetic test for
a heart rhythm disorder. This DNA test for cardiac ion channel mutations may
remove uncertainty for the patients, their families, and their physicians with respect
to establishing a diagnosis and can guide the physician in determining the best treat-
ment options for those who are genetically predisposed to potentially fatal cardiac
arrhythmias caused by long QT syndrome and related cardiac ion channel diseases.
The test examines fi ve cardiac ion channel genes for a mutation that is likely to
cause long QT syndrome. If a genetic mutation is detected, its type and location can
assist the physician in making treatment selections that could include life-style
modifi cation, prescription or avoidance of specifi c classes of drugs or the implanta-
tion of a defi brillator. A patient’s family members also benefi t from the test because
it can identify if they inherited the same mutation as the initially symptomatic
patient and may be at risk of a potentially fatal arrhythmia. These relatives often
have ambiguous fi ndings on an ECG, while the results of the FAMILION test can
answer whether or not they carry the familial mutation.
Gene Mutations Associated with Risk of Coronary Heart Disease
Plasma triglyceride levels are heritable and are correlated with the risk of coronary
heart disease (CHD). Sequencing of the protein-coding regions of the human
genome, the exome, has the potential to identify rare mutations that have a large
14 Personalized Management of Cardiovascular Disorders