Caused by one of >160 mutations (Allelic heterogeneity), Lamellar inclusions of glycosphingolipids, Most are diagnosed early in childhood & die before adulthood, Fibrotic restrictive CM can coexist with constrictive pericarditis. pathophysiology of acute coronary syndrome and heart failure Classification of acute coronary syndrome Acute Coronary Syndrome (ACS) refers to any condition attributed to obstruction of the coronary arteries which reduces blood flow to the heart, and … Detailed Causes of Restrictive CM[2][3][4][7], Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology, Cardiomyopathy: Gross excellent view of mitral valve from left atrium anterior leaflet appears to balloon a bit into the atrium. 80% of HCM patients have a mutation in either Myosin-binding protein C (. nhlbi.nih.govCardiomyopathy refers to diseases of the heart muscle. Subtypes listed below in order of decreasing severity. Absence of another identifiable cause for the HF. Most known inherited genetic defects to date are associated with hypertrophic CM. Cardiovascular disease is a common complication of diabetes responsible for 80% of … Fewer granulomas associated with better prognosis. Coronary artery disease is the leading cause of death with overall mortality of approximately 245 per 100 000 individuals in 2008. Conduction disease lasting 1-2 weeks after Abx, MOA: secondary to Antibodies & Cytokines from prior physical injury & viral infection, Patients with Pulmonary Sarcoidosis at higher risk for cardiac involvement, Thought to have an infectious or environmental trigger, as regional clustering of cases. RVR is poorly tolerated (decreased preload, decreased filling, increased myocardial O, Beta-blockers, Non-dihydropyridine-CCB (verapamil, diltiazem), Rate control may be necessary to sustain atrial kick - Amiodarone, Disopyramide, If refractory to medical therapy: AVN Ablation, Also, patient's have supranormal exercise capacity, mild ventricular dilation, and normal diastolic function, Mildly decreased contractility & EF (usually >30-50%). Cardiomyopathy is usually diagnosed with a chest X-ray, an echocardiogram (ultrasound of the heart), blood tests and a physical examination. This leads to enlargement of the inside of the ventricle.Source: U.S. Department of Health and Human Services, National Institutes of Health, National Heart Lung and Blood Institute. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. Symptoms and signs of PPCM are similar to those in patients with idiopathic dilated cardiomyopathy. Etiologies varied, including Eosinophilic granulomatosis with polyangiitis (EGP, formerly Churg-Strauss), antecedent infection (Mediterranean & African countries), and malignancies. Influenza virus (winter & spring), DNA viruses: Herpesviruses (Varicella zoster, CMV, EBV, HHV6), Parvovirus B19, Most common presentation are signs and symptoms of HF, Patients can also present with chest pain or acute MI, More rarely, tachyarrythmias (atrial or ventricular) or thromboembolic manifestations can occcur. These diseases have a variety of causes, symptoms, and treatments. Treatment — which might include medications, surgically implanted devices or, in severe cases, a heart transplant — depends on which type of ca… Mutations in this gene have been associated with a number of cardiomyopathies. Diphtheria releases a toxin that impairs protein synthesis & disrupts the conduction system. Dilated cardiomyopathy, the most common type of the disease, is characterized by an enlarged heart with stretching of the ventricle (lower chamber) and atrium (upper chamber). An irregular heart beat and fainting may occur. Usually CM is reversible, but not always. Pathophysiology Flow Chart ( Block Diagram) ... Edit this Diagram. These diseases have a variety of causes, symptoms, and treatments. In rare cases, the muscle tissue in the heart is replaced with scar tissue. Pathophysiology not fully characterized, but evolving. Sarcomeric genes identified associated with mutations causing DCM & HCM (e.g. Cardiomyopathy Pathophysiology In 2006, the American Heart Association defined cardiomyopathies as: [2] "...a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic. 1. The importance of timely diagnosis is displayed below in Figure 6. Dilated cardiomyopathy has many known and probably many unidentified causes (see table Causes of Dilated Cardiomyopathy). RadcliffeCardiology article image Figure 2: Pathophysiology of Takotsubo Cardiomyopathy. Cardiac output is decreased which activates the renin-angiotensin-aldosterone system, the sympathetic autonomic nervous system, and increase the release of the atrial natriuretic peptide. Pathophysiology of Dilated Cardiomyopathy. This often improves with appropriately aggressive supportive care. Types of Cardiomyopathy Hypertrophic cardiomyopathyoccurs when the heart muscle thickens abnormally.Dilated cardiomyopathy affects the heart's ventricles and atria. [3] [4] The many causes of Dilated CM all share the following phenotype: Enlarged heart, decreased systolic function. Alternatively called … Mutations in Titin, a large sarcomeric protein that maintains structure & participates in signaling, are the most common cause of dilated CM (approximately 20% of known cases). doi: 10.1016/j.ijcard.2011.09.077. Cardiomyopathy refers to diseases of the heart muscle. Severity of clinical disease is usually commensurate with an increasing number of mutations. Associated with an increased risk of hypertension, low plasma renin, & cardiac remodeling, More prevalent in blacks (50%) than whites (10%), FH of DCM: female carriers of X-linked CM (e.g. 2 phases of eosinophilic myocardial disease: Cardiac inflammation replaced by fibrosis with superimposed thrombosis. Common cause of sudden cardiac death from malignant arrythmias (VTach, VFib). Small vessel spasm and ischemia → small, stiff heart with rEF without dilation, Concomitant Pulmonary HTN accentuates Right HF present in most restrictive diseases, Primarily a dilated CM with restrictive component, Fibrosis limits the degree of dilation possible, Most common cause of Endomyocardial fibrosis near the equator, May comprise up to 25% of CHF in these regions, End stage of prior hypereosinophilic disease triggered by endemic parasites, Fibrosis obliterating the ventricular apex, extending to valvular apparatus, like Löffler's endocarditis, Associated with pericardial effusions, unlike Löffler's endocarditis, Fibrosis obliterating the ventricular apex, extending to valvular apparatus : Tropical endomyocardial fibrosis, Most common cause of Endomyocardial fibrosis outside of equatorial regions, Hypereosinophilic syndrome associated with myeloproliferative disorders are often secondary to chromosomal rearrangements involving platelet-derived growth factor receptor (PDGFR), creating a fusion gene yielding a constitutively active PDGFR tyrosine kinase, Treatment with Imatinib (TKI) has produced hematologic remissions and reversal of endomyocarditis, HAN : most common (MC) identifiable cause of Eosinophilia :: CHINA : most common cause of (MCC) eosinophilia. This … Read our disclaimer for details. Duchenne or Becker muscular dystrophy, Danon disease), Dietary-induced fluid retention (e.g. Chronic myocarditis is the oldest known cause of cardiomyopathy, described in literature as 'heart muscle disease,' as far back as the mid-1850s. Delineation may be arbitrary, as a study found no differences between PPCM and ePACM in the following characteristics: age, race, associated conditions, LVEF, the rate & time of recovery, maternal outcomes, Myocardial depression can quickly develop and reverse with appropriate treatment, Largely secondary to Lymphocytes, cytokines, and antibodies, Eti: 5-6 drinks (4 oz of pure EtOH) QS for 5-10years, MOA: Direct toxicity of both Alcohol & its metabolite, acetaldehyde, Genetic polymorphisms of genes encoding alcohol dehydrogenase & ACE make individuals at an increased risk of developing CM with prolonged alcohol exposure, Late: Persistent Afib, Withdrawal can worsen HF or arrhythmias Improvement can happen after 3-6months of abstinence, Excess catecholamines can cause multifocal contraction band necrosis, likely secondary to calcium overload causing direct myocyte toxicity OR. Restrictive CM is characterized by the following 6 characteristics:[2][3]. More than 20 viruses can cause dilated cardiomyopathy; in temperate zones, coxsackievirus B is most common. By David Richfield (User:Slashme)When using this image in external works, it may be cited as follows:Richfield, David (2014). Circulation 2003; 107:2227. Symptoms may include the following: 1. Dyspnea on exertion, shortness of breath, cough 3. ISSN 2002-4436. Study by van Waning et al. [1][2]. [1]. Atrial Arrhythmias, conduction disease, & CM : Formerly arrhythmogenic right ventricular dysplasia (ARVD) or cardiomyopathy (ARVC), as first described in right ventricle. Cardiomyopathy: Gross apical slice of left and right ventricles concentric hypertrophy with cavitary obliteration sudden unexpected death obstructive cardiomyopathy, Dilated Cardiomyopathy: Gross natural color close-up view of heart surgically removed for a transplantation shows aortic valve and anterior leaflet of mitral valve with cholesterol deposits endocardium of left ventricle is diffusely thickened, Cardiomyopathy: Gross montage of ventricular slices showing hypertrophy and about normal ventricular lumen size a hypertrophic non-dilated cardiomyopathy, Cardiomyopathy: Gross ventricular slices hypertrophy and extensive myocardial fibrosis a unique case of global fiber disarray with atrophy and fibrosis, Cardiomyopathy: Gross close up view of a ventricle slice, Cardiomyopathy: Gross excellent ventricular slice with hypertrophy and fibrosis a unique case of global fiber disarray with hypertrophy then atrophy and then fibrosis, Cardiomyopathy: Gross external view of globular heart with patchy fibrosis seen through epicardium, Cardiomyopathy: Gross interventricular septum showing asymmetrical hypertrophy in posterior septum, Cardiomyopathy: Gross hypertrophic cardiomyopathy obstructive excellent section through left ventricle outlet to show subvalvular narrowing case of sudden death in a 27 yo male playing basketball no history of disease, Cardiomyopathy: Gross obstructive cardiomyopathy showing aorta outflow tract with marked endocardial thickening mitral valve appears normal (Same case as previous one), Cardiomyopathy: Gross excellent view of mitral valve atrial surface showing thickening which is fibrous in body of valve and myxoid at area of free margin changes presumed secondary to insufficiency due to anterior motion, Cardiomyopathy: Gross dilated left ventricle with marked endocardial thickening this is what has been called adult fibroelastosis, Dilated Cardiomyopathy: Gross good example huge dilated left ventricle, Dilated Cardiomyopathy: Gross dilated left ventricle with marked endocardial sclerosis (an excellent example), Cardiomyopathy: Gross intact globular shaped heart, Dilated Cardiomyopathy: Gross opened left ventricle dilated with endocardial thickening good example, Cardiomyopathy: Gross globular heart external view 10 year old girl with sickle cell anemia, Cardiomyopathy: Gross horizontal sections of ventricles dilation type 10 year old girl with sickle cell anemia, Cardiomyopathy: Intermediate between hypertrophic and dilated, Cardiomyopathy Asymmetrical Septal Hypertrophy, Dilated Cardiomyopathy: Gross opened globular left ventricle natural color (very good example), Diabetic Cardiomyopathy: Gross natural color moderately hypertrophied heart shown in horizontal section hyperemic subendocardium has no microscopic lesion long standing type I diabetic patient, no significant coronary artery lesions, congestive heart failure, Dilated Cardiomyopathy: Gross natural color external view globular heart 500 gm 24yo female seven pregnancies, Cardiomyopathy: Micro H&E high mag excellent example myofiber disarray, Cardiomyopathy: Micro H&E low mag interventricular septum at junction of normal myofiber orientation with asymmetrical hypertrophy (an excellent example), Cardiomyopathy: Micro trichrome low mag bizarre vacuolated fibers with disarray and focal fibrosis excellent low mag epicardial surface, Alcoholic Cardiomyopathy: Micro plastic section lipid in perinuclear area loss of myofibrils. The different etiologies of cardiomyopathy (CM), resulting in abnormal heart structure and function are myriad. A cardiomyopathy is a primary disorder of the heart muscle. physical disruption from infiltrating amyloid fibrils. Preservation of CO until late in the disease. Infective and non-infective-related causes must be distinguished. V122I gene mutation : Amyloidosis & Heart Failure :: BRCA1/2 gene mutation : Breast CA, 10% of people >80yo & 50% of people >90yo. Heart failure with labile &/or orthostatic BP and episodic HTN. This process causes problems in the heart's electrical signaling, resulting in arrhythmias.Restrictive cardiomyopathyThe ventricles become stiff and rigid due to replacement of the normal heart muscle with abnormal tissue, such as scar tissue. Symptoms range from exercise intolerance and progressive heart failure to fatal arrhythmias and sudden cardiac death. Involves interaction with genetics and environment (variable penetrance): Tafazzin gene encodes a protein expressed at high levels in cardiac & skeletal muscle. Abstract: Iron cardiomyopathy remains the leading cause of death in patients with thalassemia major. highlights the expanding role of genetics, Usually represent mutations on several domains on TTN gene (e.g. Takotsubo cardiomyopathy (TC) is characterized by reversible ventricular dysfunction, not limited to the distribution of an epicardial coronary artery. Can cause fatal myocarditis, HF, heart block, myocardial fibrosis and cardiomyopathy. Path on endomyocardial biopsy: infiltration with lymphocytes ad mononuclear cells with a high proportion of eosinophils. Fatigue 2. This may include heart valves, mural endocardium or the endocardium that covers implanted material, such as prosthetic valves, pacemaker/defibrillator leads and catheters. Cardiomyopathies are diseases of the muscle tissue of the heart.Types of cardiomyopathies include dilated, hypertrophic, restrictive, and arrhythmogenic right ventricular cardiomyopathy. Treatment of cardiomyopathy. Transmitted by undercooked pork, Cat feces, organ transplant, transfusion, Vertical Transmission (~T. Figure 4, below depicts the specific mechanism with which common viruses above lead to dilated CM. often displays microinfarcts secondary to small vessel ischemia. Mutations in over 40 different genes have been described (locus heterogeneity). Restrictive CM is relatively uncommon and presents largely with symptoms of right-sided heart failure (HF) and diastolic dysfunction. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Based on ratio between severely thickened myocardium with noncompacted layer ≥ 2x as thick as compacted layer (measured in short axis view), Very frequent nonsustained Ventricular tachycardia or High PVC burden, Prevalence 1:500 (~Hereditary hemochromatosis), Risk of Sudden Cardiac Death in patients with HCM is 0.5%, Transmitted in an Autosomal Dominant pattern, HCM is age dependent, with incomplete penetrance. Definition - imprecise due to varied criteria across many international societies. Some etiologies (e.g. Dilated cardiomyopathy is the most common type of cardiomyopathy.Although most cases are idiopathic, a number of conditions (e.g., coronary artery disease, wet beriberi), infections … 3 different presentations of Anthracycline toxicity, grouped by chronology: Presentation depends on the age the dose of anthracycline was received: If managed appropriately, patient can live for years with compensated cardiac function, Tyrosine kinase inhibitors (e.g. X-linked. In 2006, the American Heart Association defined cardiomyopathies as:[2], "...a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic. Highest in 1:100 in Zaria, Nigeria, due to the Hausa tribe's (predominantly located in Northern Nigeria) custom of eating kanwa, a dry lake salt, for forty days after delivery, around 1 in 1000 to 4000 live births in the United States, Mice lacking cardiac PGC-1α, a regulator of pro-angiogenic factors (e.g. Activated viral proteases (e.g enteroviral protease 2A) can activate host tyrosine kinases to facilitate further viral entry as well as facilitate viral replication and infection through degradation of dystrophin, Innate immune response depends on Toll-like receptors to recognize common antigenic patterns, Initial immune response critical to limiting viral injury, Early immunosuppresion can increase viral replication & worsen cardiac injury, Timely downregulation of resultant adaptive immune response also important to prevent autoimmune injury, Ongoing cytokine release activates matrix matalloproteinases (MMP), Inappropriately high levels of MMP can destroy the collagen & elastin cytoskeleton, potentially leading to a dilative CM physiology. Dilated Cardiomyopathy MECHANISMS IN HEART FAILURE Altered molecular expression Ultrastructural changes Myocyte hypertrophy Myocyte contractile dysfunction Apoptosis Fibroblast proliferation Collagen deposition Ventricular remodeling Pathophysiology Pathophysiology: Starling Curve Pathophysiology: Neurohumoral Adrenergic nervous system Renin-angiotensin-aldosterone axis … inherited metabolic disorders, sarcoidosis, hemachromatosis, etc.) Palpitations Others, include Thiazides, Anticonvulsants, Indomethacin, Methyldopa. 3rd trimester through 6 months postpartum, with no prior cardiac disease (often presumed). The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Approximately 30% of Dilated CM (DCM) cases are familial. Pathophysiology of Pediatric Cardiomyopathies The main pathology in dilated cardiomyopathy is systolic dysfunction. Unfortunately, because some people don’t experience any symptoms, the first sign can be sudden death. The genetic basis of hypertrophic cardiomyopathy (HCM) is well established. Guanine nucleotide-binding proteins beta-3 subunit, C825T polymorphism. Primary CM is subdivided into genetic, acquired, and mixed causes. Endocarditis is defined as an inflammation of the endocardial surface of the heart. This results from a failed attempt to ration increasingly insufficient resources following myocyte injury pictured below, in Figures 2 and 3: Figure 3, below, expounds in detail on the failed attempts of the heart to adjust to significant myocardial injury, underlying the dilated CM phenotype. tap diagram to zoom and pan Copy of New Pathophysiology of Pneumonia--You can edit this template and create your own diagram. Cyclophosphamide & Ifosfamide cardiotoxic in high doses. VEGF), develop severe DCM. Cardiomyopathies either are confined to the heart or are part of generalized systemic disorders, which may lead to cardiovascular death or progressive heart failure-related disability." Template:Richard P, Charron P, Carrier L, et al. Takotsubo's = older women after sudden intense emotional or physical stress + Global Ventricular dilatation with basal contraction, Early animal studies suggest MOA: Intense sympathetic activation with heterogeneity of myocardial autonomic innervation, diffuse microvascular spasm, &/or direct catecholamine toxicity, RF for CM: Dose dependent (occurring once cumulative life-time dose >500mg/m, Figure 5, below, depicts the MOA of Anthracycline toxicity. Paroxysmal nocturnal dyspnea 7. >100 identified mutations in Transthyretin on chromosome 13 (locus heterogeneity). Restrictive CM is the least common CM phenotype. Arrhythmogenic right ventricular dysplasia (ARVD)ARVD develops when the muscle tissue in the right ventricle dies and is replaced with scar tissue. In rare cases, the muscle tissue in the heart is replaced with scar tissue.Nonobstructive The thickened muscle makes the inside of the left ventricle smaller so that it holds less blood.ObstructiveThe septum thickens and bulges into the left ventricle.Cardiomyopathy, Disorders of Peripheral Muscle (Myopathy), Disorders of Peripheral Neuromuscular Junctions, By continuing to use the website, you consent to the use of cookies. Only one-third of all etiologies of dilated CM have been fully characterized, many of which have a genetic etiology. Traztuzumab, Imatinib). On the individual sarcomere level, HCM mutations produce modification in regulatory proteins leading to: This changes on a microscopic level lead to disorganized hypertrophy, causing a cycle of: Only 15% derived from sarcomeric mutations, Fibrosis, disorganized hypertrophy, and microvascular disease contribute to, This occurs via drag forces push the anterior mitral leaflet in contact with hypertrophied ventricular septum, Compared to individuals without HCM, the anterior mitral leaflet is anteriorly displaced & thickened from fibrous endocardial plaque deposition), Presyncope & hypotension can result from decreased preload (e.g. Progressive exercise intolerance 3. Chest pain, primarily in patients with amyloidosis or due to angina 9. Kearns-Sayre syndrome)/Arrhythmogenic ventricular dysplasia/Hemochromatosis/associated with other systemic disease/Susceptibility to immune-mediate myocarditis, "Minimally dilated CM"/Hemochromatosis/Amyloidosis/Hypertrophic CM, Arrhythmogenic Ventricular (RV>LV) dysplasia, Hemochromatosis, Inherited metabolic defects (Fabry's, Gaucher's), Radiation (breast/lung CA, Mediastinal lymphoma), Possibly related fibrotic disease (Tropical endomyocardial fibrosis, Hypereosinophilic syndrome (Löffler's endocarditis)), Hypertrophic cardiomyopathy/"pseudohypertrophic", Encodes Myosin (thick filament 15nm), Actin (thin filament 7nm),Titin (elastic elements 1nm), associated regulatory proteins, Stabilizing and connecting the cell membrane to intracellular structures, Mutations impair transmission of force and signaling for cardiac & skeletal muscle → combined cardiac & skeletal, Defects impair energy production, causing symptoms ranging from impaired cognitive function to skeletal, Phenotype depends on the distribution of maternal mitochondria during embryonic development, Prior to HAART, HIV represented 1-2% of cases of dilated cardiomyopathy. These diseases have many causes, signs and symptoms, and treatments. [1] Genetic cause include HCM, ARVD/C, ion channel disorders, storage and infiltrative diseases. Respected digital resource of independent, expert-led cardiovascular education through the provision of a personalised learning experience Hypertrophic Cardiomyopathy with or without obstruction is characterized by a thickened, hypertrophic left ventricular wall, with hyperdynamic cardiac function, and no associated hemodynamic factors (HTN, Aortic valve disease, Systemic infiltrative/storage disease). Crossref Medline Google Scholar; 11. Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that emerges towards the end of pregnancy or in the first months postpartum, in previously healthy women. SmartDraw includes 1000s of professional healthcare and anatomy chart templates that you can modify and make your own. Chronic Antibiotics, most common etiology. Cardiomyopathy (kahr-dee-o-my-OP-uh-thee) is a disease of the heart muscle that makes it harder for your heart to pump blood to the rest of your body. Additionally proposed mechanisms associated with, increased susceptibility to viral myocarditis, cross-reactivity of anti-uterine antibodies vs. cardiac muscle causing an autoimmune myocarditis, microvascular angiogenic imbalance within myocardium, abnormal prolactin cleavage fragment, induced by oxidative stress → Myocardial apoptosis, TNF-alpha & interleukin-6 elevated in PPCM compared with controls, Increased levels of C-reactive protein & Fas/Apo-1 (apoptosis signaling receptor) a/w more severe disease, sarcomeric protein mutations: TTN-truncating variant (gene encoding Titin). Cardiomyopathy refers to diseases of the heart muscle. Ischemic Cardiomyopathy. Two-thirds of dilated CM remain classified as idiopathic, reflecting the need for further investigation. This overlap in classification underscore the limitations of phenotypic classification system. Intestinal dysfcn (diarrhea, s/p resection), Most common reason for thyroid abnormalities in patient with cardiac dyscrasias are treatment of tachyarrhythmias with amiodarone. Genetic defects in Desmosomal proteins (especially plakoglobin & desmoplakin), Due to nonfunctional desmosomal proteins, patients have a distinctive phenotype, with striking woolly hair & thickened skin on palms & soles due to loss of elasticity in hair & skin, Miscellaneous (Shared Elements of Above Etiologies), Three cardinal features = Ventricular arrhythmias + Embolic events +. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Incidence varies across the world. The clinical presentation of patients with cardiomyopathy can vary widely, depending on the underlying mechanism of disease. 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