Left ventricular hypertrophy in Fabry disease: a practical approach to diagnosis

Left ventricular hypertrophy (LVH) is prevalent and associated with a poor long-term prognosis. The Framingham Heart Study, for example, showed that LVH was present in 15–20% of adults, and that, for each 50 g/m2 increment of left ventricular mass, the relative risk of cardiovascular death increased by 1.73 in men and 2.12 in women.1 Although hypertension, obesity and valvulopathies account for most causes of LVH, it is important to investigate patients with otherwise unexplained LVH since many causes are treatable. Although several electrocardiographic (ECG) criteria for the identification of LVH are available, additional investigations notably transthoracic echocardiography (echo) are invariably required due to the lack of sensitivity and specificity of ECG. The European Association of Echocardiography definition of LVH includes the demonstration of interventricular septal and/or posterior wall thickness in end-diastole ≥13 mm.2 Echocardiography can additionally interrogate valve function and characterize LVH as concentric (uniform mechanism, e.g. LV pressure overload, myocardial infiltration), or eccentric e.g. asymmetrical septal hypertrophy in hypertrophic cardiomyopathy (HCM). After the identification of LVH, a practical approach to its further assessment includes a clinical review with targeted investigations aimed firstly to exclude common causes; e.g. hypertension, obesity and valve disease. Thereafter, evaluation involves a systematic approach to exclude less common causes, e.g. hypertrophic and other cardiomyopathies, myocardial infiltration, metabolic disorders, and syndromic conditions associated with LVH. Table 1 provides a systematic scheme incorporating clinical pearls and diagnostic pointers to help target adjunctive investigations and help identify the aetiology of LVH. Disorders causing or associated with LVH are arranged in a pathological hierarchical manner with common conditions appearing first, followed by rarities. Clinical characteristics of conditions causing left ventricular hypertrophy and diagnostic pointers ∼15%: secondary cause Fundoscopic changes Lost nocturnal dip on 24 h recording 60%: ≥2 hypotensives needed to achieve control ECG: LVH (prevalence ∼30%) can predict prognosis Echo: concentric LVH CMR: may help identify aortic coarctation Genetics: not useful as polygenetic influences Laboratory: to exclude secondary causes Others: 24 h ambulatory monitoring Slow rising pulse Ejection systolic murmur Soft second heart sound ECG: LVH Echo: the trans-aortic valve gradient and the reduced valve area (beware sub-aortic membranes) CMR: nil specific Genetics: nil specific Laboratory: nil specific Body mass index Waist circumference LVH regression with weight loss ECG: attenuated LVH due to body habitus (prevalence ∼10%) Echo: concentric LVH. Epicardial fat can predict prognosis CMR: useful if poor echo windows Genetics: monogenic disorders of body fat, e.g. leptin deficiency Laboratory: endocrine causes, e.g. diabetes, thyroid, pituitary, adrenal High level endurance training Resting bradycardia LVH regression with deconditioning ECG: LVH Echo: mild concentric LVH (rarely >13 mm) and volume-loaded (dilated) LV cavity. Preserved diastolic and long-axis function CMR: no late gadolinium enhancement Genetics: nil specific Laboratory: nil specific Others: VO2 max > predicted Family history (population prevalence 1:500) Leading cause of sudden death in young athletes Risk stratification for sudden cardiac death ECG: LVH With anterior T-wave inversion, consider apical LVH Normal P–R interval Echo: asymmetrical septal hypertrophy common (but also can present with concentric or apical LVH, and right ventricular involvement). Normal LV dimensions in early stages of disease. Systolic anterior motion of mitral valve, dilated left atrium, diastolic dysfunction, and dynamic LV outflow tract obstruction CMR: intra-myocardial late gadolinium enhancement Genetics: autosomal dominant Laboratory: nil specific Others: endomyocardial biopsy: triad of myocyte and myofibril disarray, myocardial fibrosis, and small vessel disease Senile amyloid relatively common (20% of over 80 year olds) Multi-system involvement with variable signs including; proteinuria, petechiae, peripheral, and autonomic neuropathy, hepato-splenomegaly, macroglossia ECG: paradoxical low voltage QRS complexes, heart block, atrial fibrillation Echo: LVH with preserved LV size and bi-atrial dilatation Granular LV appearance (low sensitivity). Restrictive physiology, and thickened inter-atrial septum and valve leaflets CMR: global sub-endocardial late gadolinium enhancement Genetics: transthyretin gene testing (autosomal dominant) Laboratory: cross speciality investigations to differentiate between various forms of amyloid Other: Congo red staining of target organ biopsies Late presentation in females Transfusion overload Clinical constellation includes bronze skin, arthritis, diabetes (and other endocrine abnormalities), and liver cirrhosis ECG: LVH Echo: LVH with bi-ventricular and bi-atrial dilatation. Restrictive physiology CMR: rapid signal decay (2:1. Colour flow Doppler demonstration of deep perfused intertrabecular sinuses CMR: tendency to over diagnose condition Genetics: autosomal dominant in familial cases Laboratory: nil specific Lysosomal storage disease α-Galactosidase A deficiency Multi-system disease Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), heart block (later stages) Echo: predominant concentric LVH. Right ventricular and papillary muscle hypertrophy also common CMR: late gadolinium enhancement in inferior LV wall Genetics: absence of male–male transmission due to X-linked inheritance Laboratory: proteinuria Glycogen storage disease (type II) Acid maltase deficiency Early onset: survival beyond 1 year uncommon Late onset: can present in adulthood Limb-girdle and respiratory muscle weakness Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: serum CK elevated, no fasting hypoglycaemia Others: muscle biopsy Lysosomal glycogen storage disease with normal acid maltase Lysosomal-associated membrane protein 2 (LAMP2) transporter protein deficiency Males present in childhood, females in early adulthood Skeletal muscle weakness and mental retardation ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: normal acid maltase activity with reduced LAMP2 activity Others: muscle biopsy Lysosomal glycogen storage disease AMP-activated protein kinase γ2 gene mutation Multi-system involvement rare ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal dominant Fatty acid oxidation disorder Functional carnitine transporter deficiency Typically childhood presentation, but can present in adulthood Skeletal muscle weakness, hepatomegaly, abnormal fatty acid metabolism ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: by weakness and disease arrhythmias and LVH ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: mutation Laboratory: serum CK and normal or Other: muscle biopsy: red e.g. common to or inheritance with short and cardiac LVH, septal uncommon to recessive with associated with iron and diabetes, and variable and of the in early LVH in most cases ∼15%: secondary cause Fundoscopic changes Lost nocturnal dip on 24 h recording 60%: ≥2 hypotensives needed to achieve control ECG: LVH (prevalence ∼30%) can predict prognosis Echo: concentric LVH CMR: may help identify aortic coarctation Genetics: not useful as polygenetic influences Laboratory: to exclude secondary causes Others: 24 h ambulatory monitoring Slow rising pulse Ejection systolic murmur Soft second heart sound ECG: LVH Echo: the trans-aortic valve gradient and the reduced valve area (beware sub-aortic membranes) CMR: nil specific Genetics: nil specific Laboratory: nil specific Body mass index Waist circumference LVH regression with weight loss ECG: attenuated LVH due to body habitus (prevalence ∼10%) Echo: concentric LVH. Epicardial fat can predict prognosis CMR: useful if poor echo windows Genetics: monogenic disorders of body fat, e.g. leptin deficiency Laboratory: endocrine causes, e.g. diabetes, thyroid, pituitary, adrenal High level endurance training Resting bradycardia LVH regression with deconditioning ECG: LVH Echo: mild concentric LVH (rarely >13 mm) and volume-loaded (dilated) LV cavity. Preserved diastolic and long-axis function CMR: no late gadolinium enhancement Genetics: nil specific Laboratory: nil specific Others: VO2 max > predicted Family history (population prevalence 1:500) Leading cause of sudden death in young athletes Risk stratification for sudden cardiac death ECG: LVH With anterior T-wave inversion, consider apical LVH Normal P–R interval Echo: asymmetrical septal hypertrophy common (but also can present with concentric or apical LVH, and right ventricular involvement). Normal LV dimensions in early stages of disease. Systolic anterior motion of mitral valve, dilated left atrium, diastolic dysfunction, and dynamic LV outflow tract obstruction CMR: intra-myocardial late gadolinium enhancement Genetics: autosomal dominant Laboratory: nil specific Others: endomyocardial biopsy: triad of myocyte and myofibril disarray, myocardial fibrosis, and small vessel disease Senile amyloid relatively common (20% of over 80 year olds) Multi-system involvement with variable signs including; proteinuria, petechiae, peripheral, and autonomic neuropathy, hepato-splenomegaly, macroglossia ECG: paradoxical low voltage QRS complexes, heart block, atrial fibrillation Echo: LVH with preserved LV size and bi-atrial dilatation Granular LV appearance (low sensitivity). Restrictive physiology, and thickened inter-atrial septum and valve leaflets CMR: global sub-endocardial late gadolinium enhancement Genetics: transthyretin gene testing (autosomal dominant) Laboratory: cross speciality investigations to differentiate between various forms of amyloid Other: Congo red staining of target organ biopsies Late presentation in females Transfusion overload Clinical constellation includes bronze skin, arthritis, diabetes (and other endocrine abnormalities), and liver cirrhosis ECG: LVH Echo: LVH with bi-ventricular and bi-atrial dilatation. Restrictive physiology CMR: rapid signal decay (2:1. Colour flow Doppler demonstration of deep perfused intertrabecular sinuses CMR: tendency to over diagnose condition Genetics: autosomal dominant in familial cases Laboratory: nil specific Lysosomal storage disease α-Galactosidase A deficiency Multi-system disease Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), heart block (later stages) Echo: predominant concentric LVH. Right ventricular and papillary muscle hypertrophy also common CMR: late gadolinium enhancement in inferior LV wall Genetics: absence of male–male transmission due to X-linked inheritance Laboratory: proteinuria Glycogen storage disease (type II) Acid maltase deficiency Early onset: survival beyond 1 year uncommon Late onset: can present in adulthood Limb-girdle and respiratory muscle weakness Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: serum CK elevated, no fasting hypoglycaemia Others: muscle biopsy Lysosomal glycogen storage disease with normal acid maltase Lysosomal-associated membrane protein 2 (LAMP2) transporter protein deficiency Males present in childhood, females in early adulthood Skeletal muscle weakness and mental retardation ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: normal acid maltase activity with reduced LAMP2 activity Others: muscle biopsy Lysosomal glycogen storage disease AMP-activated protein kinase γ2 gene mutation Multi-system involvement rare ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal dominant Fatty acid oxidation disorder Functional carnitine transporter deficiency Typically childhood presentation, but can present in adulthood Skeletal muscle weakness, hepatomegaly, abnormal fatty acid metabolism ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: by weakness and disease arrhythmias and LVH ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: mutation Laboratory: serum CK and normal or Other: muscle biopsy: red e.g. common to or inheritance with short and cardiac LVH, septal uncommon to recessive with associated with iron and diabetes, and variable and of the in early LVH in most cases Clinical characteristics of conditions causing left ventricular hypertrophy and diagnostic pointers ∼15%: secondary cause Fundoscopic changes Lost nocturnal dip on 24 h recording 60%: ≥2 hypotensives needed to achieve control ECG: LVH (prevalence ∼30%) can predict prognosis Echo: concentric LVH CMR: may help identify aortic coarctation Genetics: not useful as polygenetic influences Laboratory: to exclude secondary causes Others: 24 h ambulatory monitoring Slow rising pulse Ejection systolic murmur Soft second heart sound ECG: LVH Echo: the trans-aortic valve gradient and the reduced valve area (beware sub-aortic membranes) CMR: nil specific Genetics: nil specific Laboratory: nil specific Body mass index Waist circumference LVH regression with weight loss ECG: attenuated LVH due to body habitus (prevalence ∼10%) Echo: concentric LVH. Epicardial fat can predict prognosis CMR: useful if poor echo windows Genetics: monogenic disorders of body fat, e.g. leptin deficiency Laboratory: endocrine causes, e.g. diabetes, thyroid, pituitary, adrenal High level endurance training Resting bradycardia LVH regression with deconditioning ECG: LVH Echo: mild concentric LVH (rarely >13 mm) and volume-loaded (dilated) LV cavity. Preserved diastolic and long-axis function CMR: no late gadolinium enhancement Genetics: nil specific Laboratory: nil specific Others: VO2 max > predicted Family history (population prevalence 1:500) Leading cause of sudden death in young athletes Risk stratification for sudden cardiac death ECG: LVH With anterior T-wave inversion, consider apical LVH Normal P–R interval Echo: asymmetrical septal hypertrophy common (but also can present with concentric or apical LVH, and right ventricular involvement). Normal LV dimensions in early stages of disease. Systolic anterior motion of mitral valve, dilated left atrium, diastolic dysfunction, and dynamic LV outflow tract obstruction CMR: intra-myocardial late gadolinium enhancement Genetics: autosomal dominant Laboratory: nil specific Others: endomyocardial biopsy: triad of myocyte and myofibril disarray, myocardial fibrosis, and small vessel disease Senile amyloid relatively common (20% of over 80 year olds) Multi-system involvement with variable signs including; proteinuria, petechiae, peripheral, and autonomic neuropathy, hepato-splenomegaly, macroglossia ECG: paradoxical low voltage QRS complexes, heart block, atrial fibrillation Echo: LVH with preserved LV size and bi-atrial dilatation Granular LV appearance (low sensitivity). Restrictive physiology, and thickened inter-atrial septum and valve leaflets CMR: global sub-endocardial late gadolinium enhancement Genetics: transthyretin gene testing (autosomal dominant) Laboratory: cross speciality investigations to differentiate between various forms of amyloid Other: Congo red staining of target organ biopsies Late presentation in females Transfusion overload Clinical constellation includes bronze skin, arthritis, diabetes (and other endocrine abnormalities), and liver cirrhosis ECG: LVH Echo: LVH with bi-ventricular and bi-atrial dilatation. Restrictive physiology CMR: rapid signal decay (2:1. Colour flow Doppler demonstration of deep perfused intertrabecular sinuses CMR: tendency to over diagnose condition Genetics: autosomal dominant in familial cases Laboratory: nil specific Lysosomal storage disease α-Galactosidase A deficiency Multi-system disease Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), heart block (later stages) Echo: predominant concentric LVH. Right ventricular and papillary muscle hypertrophy also common CMR: late gadolinium enhancement in inferior LV wall Genetics: absence of male–male transmission due to X-linked inheritance Laboratory: proteinuria Glycogen storage disease (type II) Acid maltase deficiency Early onset: survival beyond 1 year uncommon Late onset: can present in adulthood Limb-girdle and respiratory muscle weakness Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: serum CK elevated, no fasting hypoglycaemia Others: muscle biopsy Lysosomal glycogen storage disease with normal acid maltase Lysosomal-associated membrane protein 2 (LAMP2) transporter protein deficiency Males present in childhood, females in early adulthood Skeletal muscle weakness and mental retardation ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: normal acid maltase activity with reduced LAMP2 activity Others: muscle biopsy Lysosomal glycogen storage disease AMP-activated protein kinase γ2 gene mutation Multi-system involvement rare ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal dominant Fatty acid oxidation disorder Functional carnitine transporter deficiency Typically childhood presentation, but can present in adulthood Skeletal muscle weakness, hepatomegaly, abnormal fatty acid metabolism ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: by weakness and disease arrhythmias and LVH ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: mutation Laboratory: serum CK and normal or Other: muscle biopsy: red e.g. common to or inheritance with short and cardiac LVH, septal uncommon to recessive with associated with iron and diabetes, and variable and of the in early LVH in most cases ∼15%: secondary cause Fundoscopic changes Lost nocturnal dip on 24 h recording 60%: ≥2 hypotensives needed to achieve control ECG: LVH (prevalence ∼30%) can predict prognosis Echo: concentric LVH CMR: may help identify aortic coarctation Genetics: not useful as polygenetic influences Laboratory: to exclude secondary causes Others: 24 h ambulatory monitoring Slow rising pulse Ejection systolic murmur Soft second heart sound ECG: LVH Echo: the trans-aortic valve gradient and the reduced valve area (beware sub-aortic membranes) CMR: nil specific Genetics: nil specific Laboratory: nil specific Body mass index Waist circumference LVH regression with weight loss ECG: attenuated LVH due to body habitus (prevalence ∼10%) Echo: concentric LVH. Epicardial fat can predict prognosis CMR: useful if poor echo windows Genetics: monogenic disorders of body fat, e.g. leptin deficiency Laboratory: endocrine causes, e.g. diabetes, thyroid, pituitary, adrenal High level endurance training Resting bradycardia LVH regression with deconditioning ECG: LVH Echo: mild concentric LVH (rarely >13 mm) and volume-loaded (dilated) LV cavity. Preserved diastolic and long-axis function CMR: no late gadolinium enhancement Genetics: nil specific Laboratory: nil specific Others: VO2 max > predicted Family history (population prevalence 1:500) Leading cause of sudden death in young athletes Risk stratification for sudden cardiac death ECG: LVH With anterior T-wave inversion, consider apical LVH Normal P–R interval Echo: asymmetrical septal hypertrophy common (but also can present with concentric or apical LVH, and right ventricular involvement). Normal LV dimensions in early stages of disease. Systolic anterior motion of mitral valve, dilated left atrium, diastolic dysfunction, and dynamic LV outflow tract obstruction CMR: intra-myocardial late gadolinium enhancement Genetics: autosomal dominant Laboratory: nil specific Others: endomyocardial biopsy: triad of myocyte and myofibril disarray, myocardial fibrosis, and small vessel disease Senile amyloid relatively common (20% of over 80 year olds) Multi-system involvement with variable signs including; proteinuria, petechiae, peripheral, and autonomic neuropathy, hepato-splenomegaly, macroglossia ECG: paradoxical low voltage QRS complexes, heart block, atrial fibrillation Echo: LVH with preserved LV size and bi-atrial dilatation Granular LV appearance (low sensitivity). Restrictive physiology, and thickened inter-atrial septum and valve leaflets CMR: global sub-endocardial late gadolinium enhancement Genetics: transthyretin gene testing (autosomal dominant) Laboratory: cross speciality investigations to differentiate between various forms of amyloid Other: Congo red staining of target organ biopsies Late presentation in females Transfusion overload Clinical constellation includes bronze skin, arthritis, diabetes (and other endocrine abnormalities), and liver cirrhosis ECG: LVH Echo: LVH with bi-ventricular and bi-atrial dilatation. Restrictive physiology CMR: rapid signal decay (2:1. Colour flow Doppler demonstration of deep perfused intertrabecular sinuses CMR: tendency to over diagnose condition Genetics: autosomal dominant in familial cases Laboratory: nil specific Lysosomal storage disease α-Galactosidase A deficiency Multi-system disease Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), heart block (later stages) Echo: predominant concentric LVH. Right ventricular and papillary muscle hypertrophy also common CMR: late gadolinium enhancement in inferior LV wall Genetics: absence of male–male transmission due to X-linked inheritance Laboratory: proteinuria Glycogen storage disease (type II) Acid maltase deficiency Early onset: survival beyond 1 year uncommon Late onset: can present in adulthood Limb-girdle and respiratory muscle weakness Enzyme replacement therapy available ECG: LVH, short P–R interval (early stages), accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: serum CK elevated, no fasting hypoglycaemia Others: muscle biopsy Lysosomal glycogen storage disease with normal acid maltase Lysosomal-associated membrane protein 2 (LAMP2) transporter protein deficiency Males present in childhood, females in early adulthood Skeletal muscle weakness and mental retardation ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: normal acid maltase activity with reduced LAMP2 activity Others: muscle biopsy Lysosomal glycogen storage disease AMP-activated protein kinase γ2 gene mutation Multi-system involvement rare ECG: LVH, short P–R interval, accessory pathways Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal dominant Fatty acid oxidation disorder Functional carnitine transporter deficiency Typically childhood presentation, but can present in adulthood Skeletal muscle weakness, hepatomegaly, abnormal fatty acid metabolism ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: autosomal recessive Laboratory: by weakness and disease arrhythmias and LVH ECG: LVH Echo: concentric LVH with restrictive physiology CMR: nil specific Genetics: mutation Laboratory: serum CK and normal or Other: muscle biopsy: red e.g. common to or inheritance with short and cardiac LVH, septal uncommon to recessive with associated with iron and diabetes, and variable and of the in early LVH in most cases heart muscle disorders with LVH are due to in of the cardiac metabolic or cardiomyopathy is the cardiac condition and important cause of sudden it is in the systematic scheme of LVH and early in the diagnostic of unexplained LVH. cardiomyopathy as a dilated LV in the absence of or cardiac of cardiomyopathy is the most common cardiomyopathy with clinical prevalence in the of most is autosomal in of several cardiac in in a the European of right restrictive and forms of cardiomyopathy on and may is since in many cases Although criteria for the of are several secondary forms of concentric LVH A for example, that of in disease on further is since the of are and early and may the prognosis in disease. disease is disease of metabolism in attenuated activity in most absence of the A a the of is to of is that 1 in the prevalence in the is 1 in many disorders, the condition can its is less in of a index can to the identification of additional with the in that and the of of may to the in the activity and clinical presentation of disease. Multi-system in childhood with of the complications in signs and of disease in if with Typical are in the left and in the right The of of in may account for the disease presentation in patients may increased myocardial mass and LVH, the presentation of is by in with myocardial by late enhancement are common in with observed in the stages of the disease in important is that are men to a cardiac by cardiac involvement the for gene testing in females of disease observed in and muscle and Although it is that and are in and dysfunction, to and Left ventricular hypertrophy is a in disease and is in up to of and of with LVH, the gene in up to of most cases the LVH is asymmetrical with septal and posterior wall may present in cases Right ventricular hypertrophy is also common and may to right ventricular long-axis and echo of cardiomyopathy asymmetrical septal hypertrophy with posterior left ventricular of the left with late gadolinium enhancement in the myocardial The in cardiomyopathy with involvement with is invariably present in the is the imaging of in cases Typical P–R interval due to of the P–R interval voltage signs of LVH, and studies that arrhythmias in of and of patients with of arrhythmias of the can to of but myocardial is uncommon of may from present between the of and small in and by activity or and lack of with and not left small on the and right may in young patients and is to proteinuria and in the by the of to failure by the of Early or in of and of the of in of the a practical diagnostic approach to patients with LVH After common causes of LVH and with unexplained LVH, a approach is for the identification of patients with disease with left ventricular the history is on complications of disease. a of disease the childhood a history of unexplained early or other of disease. The absence of transmission in the of a by LVH is a of X-linked may additional to in cases multi-organ involvement may right and left are clinical may proteinuria, the may identify a short P–R disease is A activity in or lack A a low level of A of may in with a cardiac of the in females is since activity may low normal or normal in up to of the females with disease. patients gene as a a as a for The involves on with the that can for to a for the of diagnostic cardiac biopsy is not required for disease. The of cardiac in patients cardiac biopsy investigations for unexplained restrictive cardiomyopathy the to the of gene testing for LVH various protein gene and causing metabolic disease and are available for diagnostic in the several the to for the most prevalent of the gene in the of and in not and/or a history with otherwise unexplained LVH. a of testing not exclude the of the mutation in index targeted mutation can to diagnose and females in that specific patients clinical on in disease is the to replacement therapy by the evaluation of and organ The of disease in the of are available for and other clinical that can the risk of clinical the cardiac and of function and of of in patients that is associated with that the of hypertrophy and the cardiac with and that the can is and organ of the or the to cardiac complications and may the most early and of cases are involves and and that are in the of a Left ventricular hypertrophy a common most LVH may to hypertension, valve or is not to conditions as disease. disease is a disease LVH and are common and the cardiac complications are a cause of a practical approach to the identification of patients with otherwise unexplained LVH and disease. of disease involves activity in and testing in the mutation is is important to identify may the most to from of the for was by of and from and and from and to The the of from The and for the of