Unexplained Left Ventricular Hypertrophy Research Articles

Prevalence and clinical characteristics of Danon disease among patients with left ventricular hypertrophy and concomitant electrocardiographic preexcitation.

BackgroundCardiac involvement in Danon disease typically manifests as left ventricular hypertrophy (LVH) and ventricular preexcitation. This study aimed to identify patients with Danon disease among patients with LVH and concurrent electrocardiographic preexcitation.MethodsElectrocardiographic preexcitation was identified in 10 of 197 patients with unexplained LVH in whom genetic testing was performed using next‐generation sequencing.ResultsThree (3/10, 30%) patients with Danon disease were found in association with different mutations in the gene of lysosome‐associated membrane protein 2 (LAMP2). Compared to seven patients without Danon disease, these three patients presented with distinctive clinical phenotypes, including onset at an earlier age (20 ± 2 years vs. 53 ± 9 years, p < 0.001), more neurological involvements (100% vs. 0, p = 0.008), higher electrocardiographic voltages (10 ± 1 mV vs. 5 ± 1 mV, p < 0.001), wider QRS complexes (163 ± 5 ms vs. 115 ± 20 ms, p = 0.006), less common asymmetric hypertrophy (0% vs. 86%, p = 0.033), and more frequent elevation of three serum enzymes (creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Intracellular vacuoles accumulation with deficiencies of LAMP2 protein was found in both cardiac and skeletal myocytes of patients with Danon disease.ConclusionIn patients with coexistent LVH and ventricular preexcitation, Danon disease is common with distinctive clinical presentations. Comprehensive assessment of these resemble patients can provide valuable findings for early identification and clinical decision making of patients with Danon disease.

IDENTIFICATION OF CARDIAC AMYLOIDOSIS AMONG A COHORT OF HYPERTROPHIC CARDIOMYOPATHY PATIENTS

While hypertrophic cardiomyopathy (HCM) is the most common cause of unexplained left ventricular hypertrophy (LVH), the phenotype of cardiac amyloidosis can mimic HCM leading to misdiagnosis. Given the substantial differences in prognosis and management, as well as novel therapies to improve

Fabry disease in cardiology practice: Literature review and expert point of view

Fabry disease is an X-linked progressive multisystemic genetic sphingolipidosis caused by deficient activity of lysosomal α-galactosidase A. Men aged>30 years and women aged>40 years most often present with unexplained left ventricular hypertrophy, usually concentric and non-obstructive, but sometimes mimicking sarcomeric hypertrophic cardiomyopathy, particularly when isolated, as in the cardiac or late-onset variant of the disease. In hypertrophic cardiomyopathy cohorts, up to 1% of patients have been diagnosed with Fabry disease. Frequent cardiac symptoms include chronotropic incompetence, severe conduction disturbances and arrhythmias, heart failure and sudden death, and cardiovascular complications are currently the leading cause of death at a mean age of 55 years in men and 66 years in women. Complementary to screening for extracardiac manifestations, the initial cardiac evaluation should include long-duration electrocardiogram recordings, echocardiography and late gadolinium and T1 mapping magnetic resonance imaging. Abnormalities of a non-hypertrophied inferolateral wall at the base of the left ventricle (thinning, decreased strain, midwall fibrosis) and low native T1 signal on magnetic resonance imaging are evocative. Aggressive cardiac management may include the control of cardiovascular risk factors, anticoagulation, permanent cardiac pacing and/or an implantable cardioverter defibrillator device, while antiarrhythmics and beta-blockers should be used with caution. Specific therapy should be initiated at the earliest stage, when the first structural or functional cardiac abnormalities are detected, and should include enzyme replacement therapy (available since 2001) or chaperone therapy (available since 2016) (the use of which is limited to patients with Fabry disease and an amenable α-galactosidase A [GLA] gene mutation).

Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with MYL2-R58Q-Mediated Apical Hypertrophic Cardiomyopathy Show Hypertrophy, Myofibrillar Disarray, and Calcium Perturbations.

Hypertrophic cardiomyopathy (HCM), characterized by unexplained left ventricular hypertrophy, is one of the most common heritable cardiovascular diseases. The myosin regulatory light chain (MYL2) mutation R58Q has been associated with severe cardiac hypertrophy and sudden cardiac death (SCD). Herein, we provide the first patient-specific, induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of MYL2-R58Q. The MYL2-R58Q iPSC-CMs were nearly 30% larger than control iPSC-CMs at day 60. The percentage of myofibrillar disarray and cells with irregular beating in MYL2-R58Q iPSC-CMs was significantly higher than that in control cells. MYL2-R58Q iPSC-CMs had significantly decreased peak ΔF/F0 of calcium transients and delayed decay time than controls. Additionally, the L-type Ca2+ channel (LTCC) (ICa,L) density at 0mV was reduced significantly by 45.3%. Overall, the MYL2-R58Q iPSC-CMs recapitulated the HCM phenotype by exhibiting hypertrophy, myofibrillar disarray, increased irregular beating, decreased [Ca2+]i transients, and unexpectedly a nearly 50% reduction in LTCC peak current.

Ratio of Fabry disease in patients with idiopathic left ventricular hypertrophy: A single-center study in Turkey.

Objective:Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism which arises due to deficient or absent activity of lysosomal α-galactosidase A (α-Gal A). This may be associated with increased left ventricular (LV) wall thickness and may mimic the morphological features of hypertrophic cardiomyopathy. The purpose of this study was to define the ratio of occurrence of FD to the manifestation of unexplained left ventricular hypertrophy (LVH).Methods:We studied a prospectively assembled a consecutive cohort of 190 patients with unexplained LVH on echocardiography. The criterion for LVH diagnosis was a maximum LV wall thickness of 13 mm or greater. All patients were tested for mutations in the GLA gene.Results:The majority of patients were male (n=119, 63%) and the mean patient age was 47.2±15 years. In 190 patients diagnosed with LVH, we identified 2 patients (1.05%) with documented GLA mutations [c.427G>A (p.A143T)(p.Ala143Thr)] and [c.937G>T (p.D313Y)(p.Asp313Tyr)]. After the family screening, 3 additional patients with FD were identified in 2 families, including 5 individuals who are now receiving enzyme replacement therapy.Conclusion:We identified 2 index patients with FD and unexplained LVH. Cardiologists should, therefore, be aware of FD in cases of unexplained LVH. Family screening is crucial for the earlier identification of unaffected new patients who may benefit from enzyme replacement therapy.

Prevalence of Fabry Disease in Korean Men with Left Ventricular Hypertrophy.

BackgroundFabry disease is an X-linked recessive disorder caused by deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A). Previous studies identified many cases of Fabry disease among men with left ventricular hypertrophy (LVH). The purpose of this study was to define the frequency of Fabry disease among Korean men with LVH.MethodsIn this national prospective multicenter study, we screened Fabry disease in men with LVH on echocardiography. The criterion for LVH diagnosis was a maximum LV wall thickness 13 mm or greater. We screened 988 men with LVH for plasma α-Gal A activity. In patients with low α-Gal A activity (< 3 nmol/hr/mL), we searched for mutations in the α-galactosidase gene.ResultsIn seven men, α-Gal A activity was low. Three had previously identified mutations; Gly328Arg, Arg301Gln, and His46Arg. Two unrelated men had the E66Q variant associated with functional polymorphism. In two patients, we did not detect GLA mutations, although α-Gal A activity was low on repeated assessment.ConclusionWe identified three patients (0.3%) with Fabry disease among unselected Korean men with LVH. Although the prevalence of Fabry disease was low in our study, early treatment of Fabry disease can result in a good prognosis. Therefore, in men with unexplained LVH, differential diagnosis of Fabry disease should be considered.

PREPHENOTYPIC MYOCARDIAL CRYPT MORPHOLOGY IN HYPERTROPHIC CARDIOMYOPATHY

SESSION TITLE: Cardiovascular Disease 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a genetic heart disease first described over 50 years ago. More recently, cardiovascular magnetic resonance imaging has advanced our understanding of the phenotypic heterogeneity of the disease. CASE PRESENTATION: A 21-year-old man presented after a syncopal episode while playing soccer. He reported two prior similar events that occurred ten years ago. Family history further revealed a father who was diagnosed with non-obstructive hypertrophic cardiomyopathy at a young age. Electrocardiogram showed normal sinus rhythm. Transthoracic echocardiogram identified mild concentric left ventricular hypertrophy with preserved left ventricular ejection fraction and an interventricular septal end diastolic diameter estimated at 11-millimeters. Cardiac magnetic resonance imaging (CMR) was done, which revealed a maximal wall thickness of 13-millimeters in the basal septum. There was no systolic motion of the mitral valve or evidence of flow acceleration of left ventricular outflow tract. However, myocardial crypts were noted in the basal inferior wall. These findings represent a distinctive, but unclear morphology of hypertrophic cardiomyopathy currently thought to be more prevalent in phenotype-negative patients. A four generation family pedigree of the patient was obtained. His paternal family history was notable for ischemic cardiac disease in several members but only his father had an established diagnosis of hypertrophic cardiomyopathy. Maternal family history was unremarkable for any cardiovascular disease. Father underwent genetic testing, which revealed that he was heterozygous for the p.R502W pathogenic mutation in the myosin binding protein gene (MYBPC3). Patient was then discharged home on a Life Vest with a plan for genetic testing as outpatient. Genetic testing was also offered to the other family members. DISCUSSION: HCM is an autosomal dominant genetic cardiomyopathy with most mutations having a high penetrance. In HCM, the common phenotypes encountered on Echo or Cardiac MRI are unexplained left ventricular hypertrophy, especially asymmetric, involving the septum/anterolateral wall, increased LV outflow tract gradient and systolic anterior motion of the mitral valve leaflets. Left ventricular myocardial crypts found on cardiac MRI can serve as a good ‘pre-phenotypic’ imaging marker of HCM that can help identify family members of HCM affected families to undergo genetic testing. They occur with variable frequency, but represent a distinctive morphological expression of HCM. CONCLUSIONS: Myocardial crypt identification by cardiac magnetic resonance is emerging as a potential marker for earlier recognition of genotype positive patients at risk of developing clinical hypertrophic cardiomyopathy. This case emphasizes this clinical implication and reinforces the importance of careful history taking in diagnostic decision making. Reference #1: Maron MS, Rowin EJ, Lin D et al. Prevalence and clinical profile of myocardial crypts in hypertrophic cardiomyopathy. Circ Cardiovasc Imaging 2012;5:441-7. Reference #2: Rowin EJ, Maron MS. Myocardial crypts in hypertrophic cardiomyopathy: the new gang in town. Eur Heart J Cardiovasc Imaging 2012;13:281-3. DISCLOSURES: no disclosure on file for Shantal Gupta; No relevant relationships by Sharana Hegde, source=Web Response No relevant relationships by Jae Kim, source=Web Response No relevant relationships by Anupama Rao, source=Web Response

Novel Pharmacotherapy in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited disease characterized by unexplained left ventricular hypertrophy. Although it is estimated to affect 1 out of 500 people, the HCM gene carrier prevalence is much more common, probably as high as 1 in 200 people. Most affected individuals have a normal life expectancy, whereas some patients may develop sudden cardiac death or end-stage heart failure. Despite significant developments in the treatment of HCM with surgical, interventional, and device-based procedures, the main focus of current pharmacological therapy has not evolved from the basic objectives of relief of symptoms and improvement in functional capacity. To date, no medical treatment has been shown to prolong survival or reduce the risk of sudden cardiac death. In recent decades, research focus in HCM has shifted to identify the treatments which are able to alter the natural pathophysiological process of this disease. This article reviews the currently recommended and frequently used medications (beta-blockers, nondihydropyridine calcium channel blockers, and disopyramide) and emerging pharmacological treatment options in the management of HCM. The mechanism of action and latest clinical trials of the novel agents are discussed in greater detail.

Genotypic and Phenotypic Correlation Regarding Expression Level of Myosin Heavy Chain (Myh7) Gene Polymorphisms in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM), where it can be seen as unexplained left ventricular hypertrophy, is the most common inherited cardiac disorder. This condition is a major cause of sudden death. The clinical phenotype is heterogeneous, and mutations in a number of sarcomeric contractile protein genes are responsible for causing HCM, which is usually inherited as an autosomal dominant trait. The mode of inheritance can differ from those of HCM caused by mutations in sarcomere genes. Detailed clinical evaluation and mutation analysis are, therefore, important in providing an accurate diagnosis in order to enable genetic counseling, prognostic evaluation and appropriate clinical management. This Review summarizes current knowledge on the genetics regarding beta myosin heavy chain gene (MYH7), disease mechanisms, and correlations between phenotype and genotype in patients with HCM.

Awareness of Fabry disease in cardiology: A gap to be filled

IntroductionIn adults, unexplained left ventricular hypertrophy is usually due to sarcomeric hypertrophic cardiomyopathy (HCM). Fabry disease (FD) is rare but may mimic sarcomeric HCM, and has an adverse prognosis in the absence of specific treatment. We aimed to assess cardiologists’ awareness of FD based on data from the Portuguese Registry of Hypertrophic Cardiomyopathy. MethodsA total of 811 index patients, aged 55 ± 16 years, 486 (59.9%) male, were included. Three groups were characterized: A – 128 patients, 74 (57.8%) male, with pathogenic or likely pathogenic mutation(s) in sarcomeric genes; B – 234 patients, 146 (62.4%) male, with negative genetic testing; and C – 449 patients, 266 (59.2%) male, no genetic testing performed. The groups were compared in terms of whether FD was excluded in the registry. Potential red flags for FD were also analyzed and compared between groups. ResultsPatients in group A were younger and more frequently had familial HCM (A – 53.9% vs. B – 20.1% vs. C – 18.3%; p <0.001). FD was recorded as excluded in 217 (26.8%), similar in all groups; GLA gene testing was performed in only 50/217 patients (A – 48.6%, B – 25.7%, p = 0.019; C – 13.4%, p = 0.036 for B vs. C), mostly in women (p <0.001) in groups B and C. Alpha-galactosidase A (α-Gal A) activity was assessed in 39/217 (18%) patients, with no difference between groups, but more often in men (p = 0.005). Among patients with potential red flags for FD, only 46.7% underwent specific tests (GLA gene testing and/or α-Gal A activity). When GLA genotyping was performed no mutations were identified. ConclusionsThere is a need to improve cardiologists’ alertness for the identification of FD among the Portuguese HCM population.

Common presentation of rare diseases: Left ventricular hypertrophy and diastolic dysfunction

Left ventricular hypertrophy may be a consequence of a hemodynamic overload or a manifestation of several diseases affecting different structural and functional proteins of cardiomyocytes. Among these, sarcomeric hypertrophic cardiomyopathy (HCM) represents the most frequent cause. In addition, several metabolic diseases lead to myocardial thickening, either due to intracellular storage (glycogen storage and lysosomal diseases), extracellular deposition (TTR and AL amyloidosis) or due to abnormal energy metabolism (mitochondrial diseases). The recognition of these rare causes of myocardial hypertrophy is important for family screening strategies, risk assessment, and treatment. Moreover, as there are specific therapies for some forms of HCM including enzyme substitution and chaperone therapies and specific treatments for TTR amyloidosis, a differential diagnosis should be sought in all patients with unexplained left ventricular hypertrophy. Diastolic dysfunction is a key feature of HCM and its phenocopies. Its assessment is complex and requires evaluation of several functional parameters and structural changes. Severe diastolic dysfunction carries a negative prognostic implication and its value in differential diagnosis is limited.

Obesity and sudden cardiac death in the young: Clinical and pathological insights from a large national registry.

Aims Obesity is an increasing public health problem and a risk factor for cardiovascular diseases. The aim of the study was to determine the main features and aetiologies in a large cohort of sudden cardiac deaths that occurred in obese subjects. Methods Between 1994 and 2014, 3684 consecutive cases of unexpected sudden cardiac death were referred to our cardiac pathology centre. This study was confined to young individuals (age ≤ 35 years) for whom information about body mass index was available and consisted of 1033 cases. Results Two-hundred and twelve individuals (20%) were obese. In obese sudden cardiac death victims the main post-mortem findings were: normal heart (sudden arrhythmic death syndrome) ( n = 108; 50%), unexplained left ventricular hypertrophy ( n = 25; 12%) and critical coronary artery disease ( n = 25; 12%). Less common were hypertrophic cardiomyopathy ( n = 4; 2%) and arrhythmogenic right ventricular cardiomyopathy ( n = 4;2%). When compared with non-obese sudden cardiac death victims, sudden arrhythmic death syndrome was less common (50% vs. 60%, P < 0.01), whereas left ventricular hypertrophy and critical coronary artery disease were more frequent (12% vs. 2%, P < 0.001 and 12% vs. 3%, P < 0.001, respectively). The prevalence of critical and non-critical coronary artery disease was significantly higher in obese individuals (23% vs. 10% in non-obese individuals, P < 0.001). Conclusions Various conditions underlie sudden cardiac death in obesity, with a prevalence of sudden arrhythmic death syndrome, left ventricular hypertrophy and coronary artery disease. The degree of left ventricular hypertrophy measured by heart weight is excessive even after correction for body size. Almost one in four young obese sudden death patients show some degree of coronary artery disease, underscoring the need for primary prevention in this particular subgroup.

Frequency of cardiac amyloidosis inpatients with unexplained left ventricular hypertrophy: The Caribbean Amyloidosis Study

Afro-Caribbean regions might have a high prevalence of transthyretin cardiac amyloidosis due to their shared ancestry with Afro-American populations, where a high prevalence of Val122Ile variant of the transthyretin gene has been found. Val122Ile variant is associated with late onset cardiac amyloidosis. Still, the prevalence of cardiac amyloidosis disease (CAM) inpatients presenting with unexplained left ventricular hypertrophy (LVH) in these settings is not known. The aim of this study was to determine the prevalence of cardiac amyloidosis in a consecutive cohort of patients with unexplained left ventricular hypertrophy. Three centres in Fort de France, Trinité (Martinique) and Basse-Terre (Guadeloupe) participated. Patients were consecutively enrolled if they have wall thickness > 15 mm at echocardiography. The first diagnosis line was based on findings of an abnormal cardiac fixation of bone tracer and/or a monoclonal gammapathy. Patients with such abnormalities were then referred for a more complete set of procedures including gingival or cardiac biopsies, MRI, and transthyretin gene sequencing. We present here the preliminary results of the first 127 patients enrolled. Mean age was 65 ± 11 years. Mean septal thickness was 16.2 ± 2.3 mm and posterior wall 14.6 ± 2.1 mm. Diagnosis was accurate in all but 9 patients. Cardiac amyloidosis was found in 40 patients (33.9%), including 34 with transthyretin cardiac amyloidosis (CATTR) and 6 patients with AL amyloidosis. Male gender was found in 25/34 (78%) patients with CATTR. Transthyretin cardiac amyloidosis is very frequently observed inpatients with unexplained left ventricular hypertrophy in The French Caribbean's.

Enhancing the diagnosis of Fabry disease in cardiology with targeted information: A before – after control – impact study

Cardiac complications in Fabry disease are frequent and dominated by a high frequency of left ventricular hypertrophy; therefore, cardiologists may have an essential role in screening for this disease. Providing cardiologists with targeted information on Fabry disease would be valuable and could reduce both diagnostic and therapeutic delays. The aim of this study was to evaluate the efficiency of such strategy for Fabry screening. We conducted a before–after control–impact study by comparing observations made before and after targeted information on Fabry disease among cardiologists. The information on Fabry disease consisted of (1) an educational booklet, (2) oral information and (3) screening kits. The programme was evaluated at the end of a 12-month study period. Forty-two cardiologists participated to this study. None of them had conducted screening test and new diagnostic for Fabry disease in the 3 years prior the information. After the information, screening with dried blood spots was performed in 55 patients (ranged 18–77 years, men: 39) with cardiac monitoring for supposed sarcomeric hypertrophic cardiomyopathy ( n = 41) or unexplained left ventricular hypertrophy ( n = 14) from January 2015 to January 2016. Two new cases of Fabry disease were diagnosed (3.4%) in two men (ages 58 and 51 years). The information was deemed relevant in both content and structure and was deemed useful for everyday practice. Cardiologists valued the targeted information on Fabry disease. This information had a direct clinical impact by allowing the diagnosis of two new families with Fabry disease.

Cardiac Amyloidosis with Heart Failure and Middle Range Ejection Fraction

Introduction Cardiac amyloidosis (CA) is a disease with a difficult diagnosis, limited management and a reserved prognosis., A high level of suspicion is necessary for its identification. There are some clinical clues, such as elderly individuals with unexplained left ventricular hypertrophy (LVH), heart failure with preserved ejection fraction (HFpEF) and restrictive pattern, dissociation between LVH on echocardiography and low voltage on the electrocardiogram, among others., CA can occur with several hemodynamic forms and patterns of remodeling, according to the disease [...]

Impact of Demographic Features, Lifestyle, and Comorbidities on the Clinical Expression of Hypertrophic Cardiomyopathy.

Felix qui potuit rerum cognoscere causas Happy is he who has been able to learn the causes of things––Virgil, Georgiche, II, 489 Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease defined clinically by the presence of unexplained left ventricular (LV) hypertrophy (LVH).

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease.

GW28-e0050 Assessment 2D and 3D global longitudinal Strain of abnormal LV myocardial deformation properties Using 3D Speckle-Tracking Echocardiography in young HCM

Hypertrophic cardiomyopathy (HCM) is a disease predisposes to unexplained left ventricular (LV) hypertrophy and dysfunction and non-dilated ventricular chambers associated unusual myocardial mechanics. The most serious complications of HCM is sudden death for young subclinical patients, thus,

Fabry disease.

Fabry disease resulting from a deficiency of α-galactosidase A leads to the accumulation of globotriaosylceramide in various organs. Because the disease is an X-linked recessive disorder, males tend to develop more symptoms and more severe symptoms than females. There are also some variants of Fabry disease, and cardiac variant (cardiac Fabry disease) has the dysfunctions only inheart. Cardiac manifestations in Fabry disease are initially symmetrical and concentric left ventricular hypertrophy, and later progressive cardiac dysfunction with localized thinning of the basal posterior wall. In recent years, enzyme replacement therapy has been performed as a treatment for Fabry disease, and the initiation of this therapy is expected before the cardiac fibrosis develops. Therefore, early diagnosis of Fabry disease is essential, and echocardiography is an indispensable tool for clinical practice of this disease. Then, it is necessary to remember this disease as a differential diagnosis when encountering unexplained left ventricular hypertrophy.

Fabry disease and its cardiac involvement.

Fabry disease (FD) is an X‐linked lysosomal storage disorder that results from a deficiency of α‐galactosidase A activity. This enzymatic defect leads to the progressive accumulation of glycosphingolipids throughout the body and causes multisystemic problems including neurological, ocular, skin, renal, and cardiac manifestations in classical type of FD. The majority of patients with this disease have cardiac involvement that is mainly manifested as left ventricular hypertrophy (LVH). A cardiac variant of FD with late‐onset isolated cardiac manifestation has also been recognized. Recent studies have revealed that the prevalence of FD in patients with unexplained LVH is about 1%. Cardiac involvement of FD is associated with significant morbidity and early death due to heart failure or ventricular arrhythmias. As disease‐specific enzyme replacement therapy is now available for FD, correct diagnosis is important.