Heart & vascular pathology
Cardiomyopathy
Hypertrophic cardiomyopathy
Authors: Anum Masood, M.B.B.S., Aliya N. Husain, M.D.
Last staff update: 12 November 2024 (update in progress)
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: Hypertrophic cardiomyopathy
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Masood A, Husain AN. Hypertrophic cardiomyopathy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/heartHCM.html. Accessed December 25th, 2024.
Definition / general
- Disease inherited in an autosomal dominant pattern involving sarcomere proteins (Eur J Heart Fail 2020;22:228)
- Consists of left ventricular hypertrophy, fibrosis and hypercontractility (Eur J Heart Fail 2020;22:228)
Essential features
- Genetic disorder that consists of left ventricular hypertrophy and hypercontractility
- Hallmarks of histological diagnosis include myocyte hypertrophy, fibrosis and disarray
- Mechanisms of hypertrophic cardiomyopathy (HCM) consist of left ventricular hypertrophy, which leads to increased muscle mass that the existing vasculature cannot support
- Hypertrophy may be symmetric or asymmetric; asymmetric is more commonly seen and is found at the septum
Terminology
- Hypertrophic obstructive cardiomyopathy
- Asymmetric septal hypertrophy
ICD coding
Epidemiology
- Previously thought to be a disease only of youth but average age at diagnosis is increasing (Circ Heart Fail 2020;13:e007230)
- Can present from infancy to seventh decade of life (Int J Cardiol Heart Vasc 2020;27:100503)
- M:F = ~3:2 (Circ Heart Fail 2020;13:e007230)
- 20 million people are thought to be suffering from hypertrophic cardiomyopathy worldwide (JACC Heart Fail 2018;6:376)
Sites
- Primarily affects the left ventricle of the heart
Pathophysiology
- Mechanisms of hypertrophic cardiomyopathy consist of left ventricular hypertrophy, which leads to increased muscle mass that the existing vasculature cannot support
- Lumen of the coronary arteries also narrows due to wall hardening
- All of these phenomena lead to myocardial ischemia (Int J Cardiol Heart Vasc 2020;27:100503)
- Left ventricular hypertrophy causes decreased compliance and outflow obstruction (Eur J Heart Fail 2020;22:228)
Etiology
- More than 400 different known mutations (mostly missense) in 9 different genes
- Most common are mutations affecting cardiac beta myosin heavy chain (MYH7) and myosin binding protein C (MYBPC) (Eur J Heart Fail 2020;22:228)
- May be associated with phenotypic variations like Fabry disease and Friedreich ataxia (Int J Cardiol Heart Vasc 2020;27:100503)
Clinical features
- Common symptoms include chest pain and breathlessness upon exertion; exercise capacity decreases (Eur J Heart Fail 2020;22:228)
- Sudden cardiac death can occur in younger patients who have few or no symptoms (Int J Cardiol Heart Vasc 2020;27:100503)
- On physical exam, findings may include systolic thrill at left sternal border, pulsus paradoxus, elevated "a" wave on JVP and a B4 on auscultation (Int J Cardiol Heart Vasc 2020;27:100503)
Diagnosis
- Transthoracic echocardiography (Int J Cardiol Heart Vasc 2020;27:100503)
- Cardiac magnetic resonance (CMR) is used if assessment is difficult using echocardiography (Int J Cardiol Heart Vasc 2020;27:100503)
- Genetic testing and DNA analysis may also be performed (Int J Cardiol Heart Vasc 2020;27:100503)
Laboratory
- Cardiac enzymes such as creatinine phosphokinase and troponins
- In one study, 42 out of 98 HCM patients had a minimum serum high sensitivity cardiac troponin T (hs-cTnT) level of 14 ng/L (J Cardiol 2014;63:140)
- Mean hs-cTnT level was 12.37 ng/L
- Thus, hs-cTnT was elevated in a significant number of HCM patients
- In another study, abnormal creatine kinase MB elevation was seen in 64% of HCM patients (Circ J 2016;80:218)
Radiology description
- EKG shows ST segment and T wave changes (Int J Cardiol Heart Vasc 2020;27:100503)
- Transthoracic echocardiography should show ventricular wall thickness ≥ 15 mm in at least one segment or alternatively, ≥ 13 mm in someone with a first degree relative who has HCM (Int J Cardiol Heart Vasc 2020;27:100503)
- Cardiac magnetic resonance imaging may highlight myocardial fibrosis after paramagnetic contrast is used (Int J Cardiol Heart Vasc 2020;27:100503)
Radiology images
Images hosted on other servers:
Mid apical hypertrophy (arrow)
Prognostic factors
- Left ventricular mass index can foretell if major cardiac events, such as mortality, transplantation or arrhythmias, will occur and myocardial fibrosis predicts arrhythmias in people with HCM (Int J Cardiovasc Imaging 2021;37:2027)
- FT (feature tracking) strain analysis also gives information on ventricular dysfunction and risk stratification (Int J Cardiovasc Imaging 2021;37:2027)
- Nonobstructive HCM usually has a good prognosis
- If it has been present long term, it may evolve into dilated cardiomyopathy
- Obstructive HCM can lead to pulmonary congestion and heart failure
- Rarely, arrhythmias may also occur (Int J Cardiol Heart Vasc 2020;27:100503)
Case reports
- 39 year old man with sudden cardiac death (Transplant Proc 2022;54:2703)
- 43 year old man with an apical left ventricular aneurysm and midhypertrophic cardiomyopathy obstruction and a 63 year old man with apical hypertrophic cardiomyopathy (J Cardiothorac Surg 2021;16:360)
- 57 year old man with chest pain and T wave inversions (Eur Heart J Case Rep 2020;5:ytaa493)
Treatment
- Beta blockers and nondihydropyridine calcium channel blockers are used to reduce left ventricular outflow tract (LVOT) obstruction (Eur J Heart Fail 2020;22:228)
- Arrhythmias are treated with sotalol, amiodarone and disopyramide
- Catheter / surgical ablation may be performed for atrial fibrillation (Eur J Heart Fail 2020;22:228)
- Septal myectomy and alcohol septal ablation (ASA) are useful for obstructive HCM if the patient is refractory to drugs (Eur J Heart Fail 2020;22:228)
- Heart transplantation is indicated when HCM has reached the end stage and there is severe left ventricular or diastolic dysfunction (Int J Cardiol Heart Vasc 2020;27:100503)
- Future of treatment may involve genome editing (Eur J Heart Fail 2020;22:228)
Gross description
- Main gross findings include left ventricular hypertrophy; asymmetric hypertrophy is more common than symmetric and is found at the septum (Int J Mol Sci 2024;25:1275)
- There may also be subaortic mitral valve fibrosis (Int J Mol Sci 2024;25:1275)
- If the HCM has been progressing, dilation of ventricle can occur (Int J Mol Sci 2024;25:1275)
- White scars due to fibrous tissue buildup can be observed in ventricles (Int J Mol Sci 2024;25:1275)
Gross images
Contributed by Aliya N. Husain, M.D. and Saranya Singaravel, M.B.B.S.
Asymmetric hypertrophy
Transverse section
Microscopic (histologic) description
- Hallmarks of histological diagnosis include myocyte hypertrophy, fibrosis and disarray (Int J Mol Sci 2024;25:1275)
- Cells are abnormally branched with hyperchromatic and enlarged nuclei (Int J Mol Sci 2024;25:1275)
- Fibrosis is present interstitially between myocytes, around capillaries in a perivascular pattern or forms scar / replacement tissue after myocyte death (Int J Mol Sci 2024;25:1275)
Microscopic (histologic) images
Contributed by Aliya N. Husain, M.D. and Saranya Singaravel, M.B.B.S.
Hypertrophied cardiomyocytes with fibrosis
Hypertrophied cardiomyocytes with focal calcifications
Hypertrophied cardiomyocytes with disarray and fibrosis
Hypertrophied cardiomyocytes with nuclear enlargement
Hypertrophied cardiomyocytes with disarray
Hypertrophied cardiomyocytes
Myocardial hypertrophy
Hypertrophied cardiomyocyte
Positive stains
- The following stains have been used but are not needed for diagnosis
Negative stains
Electron microscopy description
- Electron microscopy showed a profound disruption in mitochondrial ultrastructure, in which a subset of interfibrillar mitochondria were swollen with disorganized and reduced cristae density (Circulation 2021;144:1714)
- Mitochondrial morphology is disturbed; interfibrillar mitochondria are inflated and cristae are decreased (Circulation 2021;144:1714)
Electron microscopy images
Images hosted on other servers:
Myocardium
Molecular / cytogenetics description
- MYH7 codes for beta myosin heavy chain and MYBPC3 codes for myosin binding protein C
- These genes are both responsible for HCM pathogenesis
- MYH7 gene involves p.Arg403Glu (p.R403Q) mutation (Circ Res 2021;128:1533)
Videos
Hypertrophic cardiomyopathy
by Dr. Yuichi J. Shimada
Sample pathology report
- Heart, resection for transplantation:
- Hypertrophic cardiomyopathy (750 g) (see comment)
- Comment: The left ventricle displays extensive myocyte hypertrophy and disarray with areas of replacement fibrosis.
Differential diagnosis
- Hypertension and aortic stenosis:
- Both lead to left ventricular hypertrophy (Glob Cardiol Sci Pract 2018;2018:20)
- Fabry disease:
- Causes concentric right ventricular hypertrophy (Glob Cardiol Sci Pract 2018;2018:20)
- Amyloidosis:
- Apple green birefringence on Congo red staining (Glob Cardiol Sci Pract 2018;2018:20)
- Mitochondrial disease:
- Ragged red fibers stain red with Gomori trichrome stain (Glob Cardiol Sci Pract 2018;2018:20)
Board review style question #1
Which of the following is true regarding the gross image shown above?
- Disease is inherited in an autosomal recessive pattern
- Hallmarks of histological diagnosis include myocyte hypertrophy, fibrosis and disarray
- Mainstay of diagnosis is magnetic resonance imaging
- Severe coronary atherosclerosis is the underlying etiology
Board review style answer #1
B. Hallmarks of histological diagnosis include myocyte hypertrophy, fibrosis and disarray. The gross picture shows hypertrophic cardiomyopathy and the listed features should be present if we look at the tissue sample under a microscope. Answer A is incorrect because this disease is autosomal dominant. Answer C is incorrect because echocardiography is usually used to diagnose hypertrophic cardiomyopathy. Answer D is incorrect because the pattern of hypertrophy and fibrosis does not fit ischemic heart disease.
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Reference: Hypertrophic cardiomyopathy
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Reference: Hypertrophic cardiomyopathy
Board review style question #2
A 23 year old man with a family history of cardiomyopathy fell unconscious and died on the way to the hospital. His ambulatory EKG showed ST segment and T wave changes. Upon autopsy, his heart showed myocyte disarray and fibrosis. Which of the following mutations is his condition caused by?
- Mutations affecting cardiac beta myosin heavy chain (MYH7) and myosin binding protein C (MYBPC)
- Mutations in genes encoding for pore forming alpha subunits (KCNQ1, KCNH2) of potassium channels
- Mutations in HCN4 gene
- Mutations in SCN5A gene
Board review style answer #2
A. Mutations affecting cardiac beta myosin heavy chain (MYH7) and myosin binding protein C (MYBPC). The diagnosis is hypertrophic cardiomyopathy; cardiac beta myosin heavy chain (MYH7) and myosin binding protein C (MYBPC) are mutated in this disease. Answer B is incorrect because the genetic mutations in potassium channels cause long QT syndrome, which would show QT interval prolongation on ECG. Answer D is incorrect because SCN5A gene mutations cause Brugada syndrome and would show ST segment elevation in the right precordial leads. Answer C is incorrect because HCN4 gene is mutated in idiopathic sick sinus syndrome which would have showed prolonged QRS intervals.
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Reference: Hypertrophic cardiomyopathy
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Reference: Hypertrophic cardiomyopathy
