Cardiomyopathiesclassification,oetiology and treatment
-CARDIOMYOPATHIES-CLASSIFICATION,ETIOLOGY,TREATMENT BY PIJUSH KANTI MANDAL PGT; GENERAL MEDICINEBURDWAN MEDICAL COLLEGE; BURDWAN
Cardiomyopathies The cardiomyopathies are a group of diseases that primarily effect the heart muscles and are not the result of congenital, acquired vulvular, hypertensive, coronary arterial, or pericardial abnormalities. The term cardiomyopathy should be restricted to the conditions which primarily effect the myocardium.
CARDIOMYOPATHYCLASSIFICATION Two fundamental forms of cardiomyopathy are recognised— 1)primary:- consisting of heart muscle disease predominantly involving the myocardium and/or of unknown cause. 2)secondary:-myocardial disease of unknown cause or associated with systemic disease(eg; chronic alcohol use,amyloidosis)
Clinical classification of cardiomyopathy 1.Dilated cardiomyopathy: Left and/or right ventricular enlargement Impaired systolic function Congestive cardiac failure Arrhythmias, emboli 2.Restrictve cardiomyopathy: Endomyocardial scarring or myocardial infiltration resulting in restriction to left and/or right ventricular filling 3.Hypertrophic cardiomyopathy: Dysproprtionate left ventricular hypertrophy,typically involving the septum more than the free wall with or without an intraventricular systolic pressure gradiant,ususally of a non dilated ventricular cavity.
DCM About one in three cases of heart failure is due to DCM Left and/or right ventricular systolic pump function is impaired leading to progressive dilatation Most of the cases are of unknown etiology and is termed as idiopathic DCM Secondary Causes include ischaemia,alcoholic peripartum,post infectious, viral Most common of all cardiomyopathies.
DCM--incidence Prevalence is 36 per 100,000 population Third most common cause of heart failure Most frequent cause of heart transplantation DCM accounts for approximately 10,000 deaths and 46,000 hospitalizations per year in the US Spontaneous recovery occur in one-quarter of patients
Genetic consideration One-fifth to one third of patients have familial forms of DCM Mutation in >20 genes,transmitted in AD fashion. Most commonly genes encoding Sarcomeric proteins,such as alpha cardiac actin, beta and alpha myosin, heavy chain alpha myosine,troponin T, I &C.
DCMCLINICAL MENIFESTATION: Highest incidence in middle age Blacks 2x more frequent than whites Men 3x more frequent than women Symptoms may be gradual in onset Acute presentation Misdiagnosed as viral URI in young adults Uncommon to find specific myocardial disease on endomyocardial biopsy
DCMDIAGNOSTICS… CXR (enlarged heart, CHF) Electrocardiogram (tachycardia, A-V block, LBBB, NSSTT changes, PVC’s) 24-hour Holter monitor if lightheadedness, palpitation, syncope Echocardiogram,CTI,CMRI(left ventricular dilation,with normal or minimally thickened or,thinned walls, global hypokinesis, low EF) Elevated BNP Cardiac catheterization (R/O CAD) Myocardial biopsy, rare if age >40, ischemic history, high risk profile, abnormal ECG Myocardial biopsy(rare)
DCMTREATMENT: Majority particularly>50 yrs die within 4years of onset Spontaneous improvent or stabilization in one-quarter Death due to progressive HF,V-tach SCD is a constant threat Systemic embolization is a concern Alcohol should be avoided. As should the CCBs,NSAIDs Avoid antiarrhythmics Salt restriction Fluid restriction
Initiate standard treatment of HF medical therapy ACE inhibitors diuretics Digoxin Hydralazine/nitrate combination Anticoagulation prophylaxis(EF <30%, hx of embolic events)
DCMTREATMENT CONTD..• Implantable cardiac defibrilator Cardiac transplantation This disorder is the most common indication for cardiac transplantation Survival after transplant is 80% one year 70% 5 years Left Ventricular Reduction Procedures LV-reshaping
Some other forms of DCM ALCOHOLIC CARDIOMYOPATHY: Individuals who consumes >90g/day of alcohol for many years Clinical picture resembling idiopathic or familial DCM Partially genetically predetermined (ALDH2) Abstention may halt the progression or even reverse PERIPARTUM CARDIOMYOPATHY : Cardiac dilatation with CHF develope during last trimester or within 6 months of delivery. Typically present in multiparous of age >30 yrs Unknown cause Inflammatory myocarditis, immune activation,gestational have been incriminated Symptoms,signs and management are that of IDCM Further pregnancy should be discouraged
NEUROMUSCULAR DISEASES: In duchenne’s progressive muscular dystrophy, there is mutation in gene encoding cardiac structural protein(dystrophin) lead to myocyte death. • ECG: tall ‘R’ wave in right precordial leads with R/S>1.0,associated with deep Q in limb and lateral precordial leads • Rapidly progressive HF with extended periods of apparent circulatory stability. In myotonic dystrophy there is disorders of impulse generation and AV conduction. • Evidence of overt heart disease is uncommon • Insertion of ICD or pacemaker is effective.
DCM Drugs : Adriamycin: systolic dysfunction and ventricular arrhythmia occur in a dose dependant manner with a dose of >450mg/dl Concomitant cyclphosphamide, irradiation,underlyig HF are the risk factors for cardiotoxicity. Toxicity may occur acutely but more commonly developes a median of 3 months after last dose Modification of dose along with the use of ironchelator dexrazoxone have reduced the risk of cardiotoxicity. ACE inhibitors may cause recovery of cardiac function Other drugs include Trustuzumab High dose cyclophosphamide Imatinib mesylate TCA,Lithium , cocaine abuse
DCM ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY/DYSPLASIA Familial cardiomyopathy, autosomal dominant Progressive fibrofatty tissue replacement of right ventricle and to a lesser degreee of left ventricular myocardium Mutation in genes encoding desmosomes,causes detachment in myocytes and consequent apoptosis and replacement with fibrofatty tissue. PKP2 gene mutation Ryanodine recepter gene(RyR2) mutation Patients present with right heart failure ECG:-QRS prolongation in right precordial leads with LBBB type of VT CTI,CMRI will show right ventricular dilatation and fibrofatty deposition and aneurysm Restriction from competetive sports, antiarrythmic therapy, with beta blockers &amiodarone Implantation OF ICD Cardiac transplantation
DCM TAKO-TSUBO CARDIOMYOPATHY: Also known as apical ballooning syndrome Patients presents with abrupt onset severe chest pain by a very stressfull emotion &physical events women>50 yrs ECG:ST ,withT In precordial leads, EF, troponin ECHO: akinesia of distal portion of left ventricle CAG: Normal CTI: ‘Ballooning’ of left ventricle specifically apex in end systole Reversible within 3-7 days Beta blockers is of doubtful significance in Rx LEFT VENTRICULAR NON COMPACTION(LVNC): Arrest of normal embryogenesis with persistance of deep recesses &sinusoides in the myocardiumthat characterise the embryonic heart. ECHO- Multiple deep trabeculations into the myocardium which communicate with the ventricular cavity causing left ventricular contractile dysfunction Rx- standard therapy for CHF along with chronic anticoagulation.
HCM HCM is characterised by LV hypertrophy,typically of a non-dilated chember, without any obvious cause like HTN,AoS. Two features of HCM have attracted most significance Asymetric hypertrophy of the left ventricle with the preferential hypertrophy of the IVS A dynamic left ventricular outflow tract pressure gradiant,related to narrowing of the sub aortic area.
HCM • The major abnormality of the heart in HCM is an excessive thickening of the muscle. Thickening usually begins during early adolescence and stops when growth has finished. It is uncommon for thickening to progress after this age • The left ventricle is almost always affected, and in some patients the muscle of the right ventricle also thickens • Hypertrophy is usually greatest in the septum. The muscle thickening in this region may be sufficient to narrow the outflow tract. This thickening is associated with obstruction to the flow of blood out of the heart into the aorta
HCM • Asymmetric septal hypertrophy with obstruction to the outflow of blood from the heart may occur. The mitral valve touches the septum, blocking the outflow tract. Some blood is leaking back through the mitral valve causing mitral regurgitation
HCM Dynamic LV outflow tract obstruction Outflow tract gradient (>30 mm Hg), considered severe if >50 mm Hg (occurs in 25-30% of cases leading to name hypertrophic obstructive cardiomyopathy) Diastolic dysfunction Impaired diastolic filling, filling pressure Mitral regurgitation Arrhythmias:SVT,AF,VT
HCM Approximately 30% of patients with HCM have a dynamic systolic pressure gradient in the left ventricular outflow tract caused by contact between the mitral valve leaflet(s) and the interventricular septum under resting conditions Outflow tract gradient in excess of 30 mmHg is an important cause of symptoms Gradient is simply a consequence of high velocity flow through the aortic valve, and hence does not represent a real obstruction to cardiac output .
HCM Gradient greater than 50 mmHg, the percentage of systolic volume ejected before the beginning of SAM is greatly reduced - responsible for patients symptoms.When severe, outflow tract gradient can cause dyspnea, chest pain, syncope, and predisposes to the development of atrial arrhythmias - independent predictor of disease progression and adverse outcome, including sudden death
HCM-Diagnostics Abnormal in 85-90% of cases LVH, Strain pattern Abnormal ST-T’s, giant T wave inversions Abnormal Q’s, Bundle Branch Block Left atrial enlargment Ventricular arrhthymias
HCM-Diagnostics LVH usually develops between 5-15 years of age in HCM A normal ECHO in a young child does not R/O the diagnosis Serial ECHOs are recommended up to the age of 20 yr where there is a family history of HCM An unusual form od cardiomyopathy, characterised by apical hypertrophy, is associated withgiant negative T waves and a spade shaped LV cavity; usually of a benign course.
HCM-Clinical course Clinical presentation from infancy to old age Variable clinical course 25 % of cohort achieve normal longevity Annual mortality 3% in referral centers probably closer to 1% for all patients Course may be punctuated by adverse clinical events: sudden cardiac death, embolic stroke, and consequences of heart failure Sustained V-Tach and V-Fib: most likely mechanism of syncope/ sudden death
HCM Clinical course Risk of SCD higher in children, may be as high as 6% per year, majority have progressive hypertrophy Accounts for 36% of deaths in athletes <35 years Clinical deterioration usually is slow Poor prognosis in males, young age of onset, family Hx of SCD, Hx of syncope, exercise induced hypotension (worst) Progression to DCM occurs in 10-15%
HCM--Risk factors for SCD Young age (<35 years) “Malignant” family history of sudden death Aborted sudden cardiac death Sustained VT or SVT Non-sustained VT on holter monitoring Atrial fibrillation Dilated left ventricle NYHA classes III or IV Syncope Severe hypertrophy(>3.0 cm) Abnormal BP response to exercise Coronary artery disease Strenous exercise or work
HCM-RECOMMENDATION FOR ATHELETS Low-risk older patients (>30 years) may participate in athletic activity if all of the following are absent: Ventricular tachycardia on Holter monitoring Family history of sudden death due to HCM History of syncope Severe hemodynamic abnormalities, gradient 50 mmHg Exercise induced hypotension Moderate or severe mitral regurgitation Enlarged left atrium ( 5.0 cm) Paroxysmal atrial fibrillation Abnormal myocardial perfusion
MANAGEMENT OF HCM Dehydration should be avoided Digitalis, diuretics,dihydropins, vasodilators should be avoided Drug therapy Beta-adrenergic blockers Calcium channel blockers (verapamil, diltiazem, etc) disopyramide Anti-arrhythmics – Amiodarone; Pacemakers (ICD) Myomectomy (resection of septum) Alcohol septal ablation (controlled MI through septal perforator perfusing basal septum) wall thinningdecreases in LVOTO Transplantation
Hypertensive HCM of elderly• Characteristics – Modest concentric LV hypertrophy (<22 mm) – Small LV cavity size – Associated hypertension – Ventricular morphology greatly distorted with reduced outflow tract – Sigmoid septum and “grandma SAM” echocardiographic finding only
Inherited metabolic cardiomyopathies with LVH Cardiac Danon Disease: Mutation in x-linked LAMP2. Enlarged ventricular myocytes with PAS positive inclusions. Presents in chilhhood with serious arrhythmias ECG:LVH ventricular preexcitation• Friedrich’s Ataxia: Degenerative disease caused by inadequate levels of frataxin,a protein involved in mitochondrial iron metabolism. Echo,CTI,CMRI shows symetric LVH with asymetric IVS hypertrophy Lacks cellualar disarray as of HCM
Glycogen storage disease: Mutation in PRKAG2 adenosin monophosphate-activated protein kinase.ventricular hypertrophy resembling HCM and enlarged myocytes with vacoules in the myocytes that stain for glycogen• Fabry Disease: X-linked autosomal recessive lysosomal disorder caused by deficiency of lysosomal alpha galactosidase A, leading to accumulation of glycosphingolipids in the heart leading to ventricular hypertrophy. Because of severe impairment in ventricular filling, it is sometimes classified as a restrictive cardiomyopathy Treatment consists of enzyme replacement therapy with agalsidase Beta
RCM• Hallmark: abnormal diastolic function• Rigid ventricular wall with impaired ventricular filling• Bear some functional resemblance to constrictive pericarditis• Importance lies in its differentiation from operable constrictive pericarditis• Much less common then DCM or HCM outside the tropics, but frequent cause of death in Africa, India, South and Central America and Asia primarily because of the high incidence of endomyocardial fibrosis in those regions
Restriction vs. ConstrictionHistory provide can important clues Constrictive pericarditis history of TB, trauma, pericarditis, collagen vascular disorders Restrictive cardiomyopathy amyloidosis, hemochromatosis Mixed mediastinal radiation, cardiac surgery
RCMTREATMENT:• No satisfactory medical therapy• Drug therapy must be used with caution – Diuretics for extremely high filling pressures – Chronic anticoagulation is often recommended – Vasodilators may decrease filling pressure – (?) Calcium channel blockers to improve diastolic compliance – Digitalis and other inotropic agents are not indicated
Eosinophilic endomyocardial disease: Also called loeffler’s endocarditis Cardiac damage is apparent result of toxic effect of eosinophilic proteins Endocardium of both ventricles enlarged Imaging reveals ventricular thickening of the postero basal LV wall. Management is with diuretics,venodilators, anticoagulants Glucocorticoids, hydroxurea improves survival Surgical resection of fibrotic tissue
Cardiac amyloidosis: Deposition of amyloid in the myocardium Uncommon in secondary form Diastolic dysfunction, systolic dysfunction, arrhythmias, orthostatic hypotension 2D ECHO: thickened myocardial wall with a diffuse,hyperrefractile “speckled”appearance Alkylating agent such as melphalan alng with glucocorticods appears to improove survival Heart transplantation along with bone marrow or liver kidney transplantation may help in selected patients
Other restricive cardiomyopathies Iron-overload cardiomyopathy: Should be suspected inbackground of diabetes cirrhosis and skin pigmentation Diagnosis confirmed by endomyocardial biopsy Phlebotomy Continuos subcutaneous use of iron chelators Carcinoid syndrome The carcinoid syndrome results in endocardial fibrosis ususally of right side. Stenosis/regurgitation of pulmonary, tricuspid valve. Similar lesions has been found in fenfluramine phenteramine use• Sarcoidosis: Associated witA-V block RV overload with pulmonary hypertension High degree AV block with other systemic menifestation Treated with empirical glucocortocoids