Hypertrophic cardiomyopathy (HCM) is hallmarked by the presence of left ventricular
hypertrophy (LVH) . Studies across geographic areas report a prevalence of unexplained
LVH at 0.02-0.23% in adults, and a trend of age-related prevalence, with lower rates in
patients under the age of 25 years . HCM may present in a wide variety of patterns. Its
natural history includes the development of progressive, life-limiting symptoms due to
left ventricular outflow tract (LVOT) obstruction or diastolic dysfunction, atrial
arrhythmias, heart failure (HF) associated with systolic dysfunction and risk of
ventricular arrhythmias. HCM is frequently transmitted in an autosomal dominant manner.
Known etiologies include mutations in the genes related to sarcomeric proteins, metabolic
disorders, neuromuscular diseases, and inflammation. The good prognosis depends on early
diagnosis and correct treatment strategy.
Fabry disease (FD) is an X-linked rare disease caused by mutations in the GLA gene, which
encodes alpha-galactosidase A (alpha-GAL A). Defects in alpha-GAL A leads to accumulation
of Gb3 in cells, which in turn impairs the function tissues and organs. Different GLA
variants may be related to various symptoms in different organs, and these variants can
be categorized into two types: classic and late-onset. In classic type of patients, the
disease manifestations usually occur in childhood with common symptoms such as extremity
pain, nausea, fever of unknown origin and hypohidrosis. In addition, classic FD patient
may present renal and cardiac deteriorations as well as cerebrovascular manifestations.
These manifestations may further develop into life-threatening complications at middle or
late age if untreated [4]. On the other hand, disease onset in late-onset type of FD
patients is typically in adulthood, and the clinical manifestations may be limited to
fewer organs compared to what was found in the classic type. For example, cardiac
variants IVS4+919G>A and p.N215S tend to affect the heart. Because cardiac abnormalities
in FD such as LVH is like what is observed in several heart conditions such as HCM and
cardiac amyloidosis, differential diagnosis between FD and other heart conditions is a
topic of great research and clinical interest.
Although LVH is a common feature between FD and HCM, the prevalence of FD in HCM patients
is usually limited to 1-2%. Hence, several recent reports strive to describe the
development of criteria to increase the accuracy of diagnosis of FD in HCM/LVH
populations. Seo et al. prospectively assessed the cardiac screening criteria to increase
the chance of identification of FD in HCM patients via integration of data on short PR
interval, arrhythmia, and symptoms of autonomic function. In addition, Fan et al. focused
on patients with IVST or PWT ≥ 13 mm on echocardiography, and excluded patients with
known sarcomeric gene mutations, amyloidosis, athletic heart, non-compaction
cardiomyopathy, and non-FD metabolic or syndromic conditions associated with LVH.
However, these reports are limited to single or very few centers. Moreover, it needs to
be cautious to interpret these study results due to various distribution of FD mutations
in different countries or geographic areas.
On the other hand, amyloid deposition in the heart is called cardiac amyloidosis (CA);
95% is immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR).
Hereditary (ATTRm) or wild-type (ATTRwt) depends on whether the ATTRm gene is mutated or
not. The most common mutation in Taiwan is A97S, 80% have LVH. And bone-avid tracers such
as 99mTc-PYP/DPD/HMDP could detect CA, which may be related to the microcalcification.
Recent advances in therapeutic strategies shown to be most beneficial in the early stages
of the disease have determined a paradigm shift in the screening, diagnostic algorithm,
and risk classification of patients with ATTR-CM.
Patients with HCM have genotypic and phenotypic variability. There are a number of
treatment modalities for these patients, including pharmacotherapy to control symptoms,
implantable cardiac defibrillators to manage malignant arrhythmias, and surgical myectomy
and septal ablation to decrease the left ventricular outflow obstruction. Accurate
diagnosis is vital for the perioperative management of these patients. Of note, other LVH
conditions such as FD, CA also have specific genetic background in Taiwan. In this
program, Taiwan Socieyt of Cardiology aims to establish a multi-center registry that
includes FD and selected heart conditions featured by unexplained LVH. This registry will
allow understanding of the clinical features and disease patterns of patients with
unexplained LVH in Taiwan. With systematic documentation of features of FD and non-FD
patients across Taiwan, this registry might serve as an asset for future research such as
development of scoring algorithm to identify FD more precisely, and generate the specific
"reg-flag" signs in FD, in comparison with HCM or CA in Taiwan. Moreover, with
documentation of clinical and biochemical parameters and clinical follow-up, this
registry will allow future research to understand the natural history of FD or HCM, and
long-term treatment outcomes of these diseases in Taiwan.
