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

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

3. 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

4. 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

5. 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

6. 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

7. 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

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

9. 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

10. 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

11. Four Chamber and Short-Axis Views
Nihoyannopoulos, P. et al. Eur J Echocardiogr :iii23-33iii; doi: /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

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

13. 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).

14. 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 :iii23-33iii; doi: /ejechocard/jep156

15. 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
Elevated diastolic pressures
Left ventricular pressures higher than right
Dependent on preload, can have normalization of pressures if adequately diuresed

16. 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

17. 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

18. 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

19. Treatment for Cardiac Amyloid
Usually ineffective and generally consists of supportive measures
Autologous hematopoietic cell transplantation in conjunction with melphalan therapy
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

20. 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

21. 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

22. 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