Restrictive Cardiomyopathies Zoll Lecture Series Author: Jennifer Giuseffi, MD Series Editor: Eli Gelfand, MD, FACC

Objectives Introduction Symptoms Causes Diagnosis: Treatment options Myocardial Endomyocardial Diagnosis: ECG Echocardiography invasive hemodynamics cardiac MRI Treatment options

Introduction Least common type of cardiomyopathy Increased stiffness of the myocardium  impaired diastolic filling Ventricular volumes are usually normal or reduced Wall thickness is normal or mildly increased Systolic function is typically preserved

Symptoms – similar to HF due to other causes Volume overload Fatigue Dyspnea Orthopnea Noctural dyspnea Arrhythmia  palpitations, syncope, exercise intolerance High-grade AV block (sarcoidosis, amyloid > hemochromatosis) Atrial tachyarrhythmias, including atrial fibrillation Ventricular tachyarrhythmia Reduced cardiac output Exercise intolerance Cognitive difficulties

Etiologies Myocardial causes, including infiltrative disease, are most common in the US Endomyocardial causes, specifically endomyocardial fibrosis (EMF) more common outside of US Leading cause of death in Africa, India, South and Central America, and Asia  Unclear primary cause  Possible association with eosinophilia or nutritional factors Endomyocardial biopsy of a pt with EMF http://www.hefssa.org/images/ahfr_big.jpg

Myocardial Causes Infiltrative Amyloidosis Can be primary, secondary, senile, or familial Secondary is associated with multiple myeloma Cardiac sarcoidosis Rarely isolated  usually in concert with lymphadenopathy, parenchymal lung disease Can present with syncope from ventricular tachycardia or block AV conduction abnormalities typically progressive, so low threshold for pacing +/- ICD Gaucher's Disease Fatty infiltration

Myocardial Causes Storage Diseases Hemochromatosis Therapeutic phlebotomy often reverses cardiomyopathy Fabry’s Disease Glycogen Storage Disease Deficiency of alpha-galactosidase A Enzyme replacement is available Testing is free

Endomyocardial Causes Endomyocardial Fibrosis Hypereosinophilic syndrome Carcinoid Heart disease Metastatic cancers Radiation Toxic effects of anthracycline Drugs    (serotonin, methysergide, ergotamine, mercurial agents, busulfan)

ECG Findings Large P waves indicating biatrial enlargement Conduction delays Various ST and T segment changes Ventricular tachycardias Especially in sarcoidosis In amyloid, classically – low QRS voltage

Echocardiographic Findings Non-dilated, non hypertrophied ventricles Unless infiltrative or storage disease Moderate to marked biatrial enlargement Doppler is required to assess impaired ventricular filling   Diastolic transmitral flow velocity

Four Chamber and Short-Axis Views Nihoyannopoulos, P. et al. Eur J Echocardiogr 2009 10:iii23-33iii; doi:10.1093/ejechocard/jep156 Amyloid Heart Disease Marked wall thickness (15 mm) concentrically Homogeneous texture of both ventricles Thickening of the mitral and tricuspid leaflets and right ventricle

M-mode and Parasternal Long-Axis Nihoyannopoulos, P. et al. Eur J Echocardiogr 2009 10:iii23-33iii; doi:10.1093/ejechocard/jep156 Reduced left ventricular function Note the markedly thickened RV free wall

Doppler Findings Normal systolic contraction with a rapid but ill-sustained ventricular filling seen on pulsed-wave Doppler (E-wave) and with little or no late ventricular filling (A-wave).

Top: mitral annular velocities demonstrating reduced systolic as well as diastolic velocities (E' and a') Bottom: pulsed wave-Doppler from the mitral valve demonstrating very high early diastolic velocity (E-wave), short deceleration time (<130 ms), low late diastolic filling (A-wave) of the transmitral velocity Nihoyannopoulos, P. et al. Eur J Echocardiogr 2009 10:iii23-33iii; doi:10.1093/ejechocard/jep156

Cardiac Catheterization Square-root sign (dip and plateau) In diastole, rapid early diastolic filling (dip), followed by a plateau during pressure tracings (seen in both restrictive cardiomyopathy and constrictive pericarditis) From emedicine article Pulmonary Artery Catheterization http://img.medscape.com/pi/emed/ckb/cardiology/150072-160317-3323.jpg Elevated diastolic pressures Left ventricular pressures higher than right Dependent on preload, can have normalization of pressures if adequately diuresed

Cardiac MRI High diagnostic accuracy for constrictive pericarditis, which can present similar to restrictive cardiomyopathy Important to distinguish from restrictive cardiomyopathy as definitive surgical therapy available for constrictive pericarditis Gold standard for noninvasive diagnosis of cardiac hemochromatosis

Constriction vs. Restriction Constrictive Pericarditis Physical Exam: JVP elevated Kussmal’s sign: lack of the expected inspiratory decline in JVP. Secondary to decreased compliance of the right ventricle Pericardial Knock CXR: Calcifications of the pericardium can be present Echo: Bulging of the septum to the left. Respiration variation in filling velocity (inspiration decreases PCWP  decreases pressure gradient for ventricular filling because no effect on ventricular diastolic pressure) Cath: Equalization of pressures Restrictive Cardiomyopathy Physical Exam: JVP elevated EKG: Depolarization abnormalities (such as bundle branch block), ventricular hypertrophy, pathologic Q waves, or impaired AV conduction Echo: Normal LV function. Minimal variation with respiration of filling velocity (inspiration decreases PCWP and ventricular diastolic pressure equally, no change in pressure gradient) Cath: Both show dip and plateau

Treatments Treat underlying disease in secondary causes Attempt to maintain sinus rhythm, atrial fibrillation is poorly tolerated Amiodarone Treat heart failure symptoms Diuretics and ACE inhibitors Avoid digitalis, nifedipine, ACE-I and verapamil in Amyloid Most are irreversible and require cardiac transplantation, regardless poor prognosis

Treatment for Cardiac Amyloid Usually ineffective and generally consists of supportive measures Autologous hematopoietic cell transplantation in conjunction with melphalan therapy http://www.pathology.vcu.edu/education/cardio/lab3.g.html Heart transplantation – used only if the patient has isolated cardiac amyloid ICD placement – controversial given most sudden death is related to electromechanical dissociation not ventricular arrhythmias

Treatment for Cardiac Sarcoid Goal is to control inflammation and fibrosis Glucocorticoids – thought to halt or slow process of inflammation and fibrosis Dose unclear Relapses common after taper Chloroquine, hydroxychloroquine, cyclosporine, and methotrexate – can be used for patients that are resistant to steroids ICD placement – 30-65% of deaths in patient’s with cardiac sarcoid are due to ventricular arrhythmias or conduction block

Treatment for Other Causes Hemachromatosis Treatment with serial phlebotomy EMF Poor prognosis with medical therapy (HF therapy beta blockers, diuresis) or prednisone if acute carditis Endomyocardial resection with valve replacement or repair Fabry’s – no cure Treatment with recombinant a-galactosidase A (alpha-Gal A), likely require dialysis

Take Home Points Restrictive cardiomyopathy is uncommon, however mortality is high Systolic function is typically preserved Many etiologies including both myocardial and endomyocardial causes Echo reveals impaired filling Cardiac cath shows ‘square-root sign’ MRI can be useful in distinguishing from constrictive pericarditis