Cardiac Care in pa+ents with Duchenne muscular dystrophy
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1 Cardiac Care in pa+ents with Duchenne muscular dystrophy Linda Cripe, M.D. Professor of Pediatrics The Heart Center....
2 Why are cardiologists interested in patients with Duchenne muscular dystrophy?....
3 The Heart is a Muscle TOO!!!....
4 Care of the individual with DMD is a team sport....
5 Questions we will answer today 1. What does cardiomyopathy mean? 2. What does heart failure mean? 3. Who should care for the heart? 4. When should cardiac care begin? 5. How will the heart be checked? 6. What should I watch for? 7. What treatment is available? 8. Should carriers have their hearts checked?
6 1. What does cardiomyopathy mean? The normal heart....
7 1. What does cardiomyopathy mean? Disease of heart muscle Normal Dilated 1) Muscle cell injury - cell death 2) Chamber enlarges 3) Walls become thin 4) Scar formation or fibrosis 5) Function declines
8 Cardiomyopathy DMD heart showing evidence of extensive fibrosis.
9 There are differences between skeletal and cardiac muscle Skeletal muscle Elongated multi-nucleated cells Organized into fascicles Multiple nuclei located on the periphery of the cell Cardiac muscle Rectangular shape Mono-nucleated or bi-nucleated Nuclei located centrally in the cell Often branched Important to note: Not every neuromuscular disorder manifests both skeletal and cardiac disease Skeletal muscle Cardiac muscle
10 There are differences between skeletal and cardiac muscle Cellular architecture Calcium handling Regenerative capacity When injured: Skeletal muscle regenerates from fusion of mononucleated myoblasts to the syncytium of the myofiber Cardiac muscle limited regenerative capacity injury results in increased connective tissue or scar....
11 2. What does Heart Failure mean? Complicated The heart fails to meet the demands of the body Does NOT mean the heart has failed (stopped working) Heart failure typically occurs when cardiac function is poor but can occur with good function and increased demand Body s response at first helpful but eventually causes harm PEOPLE LIVE WITH LONG LIVES WITH HEART FAILURE
12 3. Who should care for the heart? Cardiologist is a heart doctor Pediatric cardiologists Pediatrics and cardiology Adult cardiologists Adult medicine and cardiology Some cardiologists have special interests Heart failure/transplantation Neuromuscular disorders Talk to your sons doctor about finding an expert in treating heart failure
13 4. When should care begin?
14
15 4. When should cardiac care begin? Summary of Consensus Statements Cardiac investigation should: Begin at diagnosis Repeat investigation: At least biannually until age 10 Or with the onset of cardiac signs and symptoms Annually after the age of 10 Or more frequently based on cardiac signs and symptoms Prior to any major surgery Minimum recommendations generated by interested individuals....
16 5. How will the heart be checked? 1. Electrocardiogram -(ECG) a. Heart Rate b. Heart Rhythm 2. Holter monitor 3. Event monitor Electrocardiogram (ECG) Holter or Event Monitor....
17 Electrocardiogram (ECG) Abnormal at an early age Early abnormality not predictive of phenotype Type of abnormality changes with age Likely represents disease progression HR often elevated bpm above normal True tachycardia (>95 th %ile)comes with dysfunction Important to watch for changes with time Baseline important to obtain at diagnosis % Abnormal ECG < Age in years N = 105 ECGs 503
18 Typical DMD ECG
19 Holter findings in DMD patient....
20 5. How will the heart be checked? Images of the heart will be attained to evaluate structure and function
21 5. How will the heart be checked? Two common ways to obtain images of the heart: Echocardiogram Cardiac MRI....
22 5. How will the heart be checked? Echocardiogram Ultrasound evaluation of heart Evaluate anatomy and function Contraction (systole) Relaxation (diastole) Advantages: Readily available Quick Disadvantages: Image quality unreliable Scoliosis Weight and position Not accurate for RV function
23 5. How will the heart be checked? Cardiac MRI Advantages: No radiation exposure Detailed cardiac information Accurate measurements Additional information Fibrosis Metabolism Disadvantages: May involve IV placement One hour in duration Claustrophobic Expensive Sedation (younger children)
24 5. How will the heart be checked? MRI allows you to obtain information about: Cardiac function Left ventricular ejection fraction In DMD does not decline until late in the disease Left ventricular morphology DMD is not a true dilated cardiomyopathy Normal LV remodeling index at end stage with only modest chamber enlargement....
25 5. How will the heart be checked? Left ventricular myocardial tissue characterization Evidence of left ventricular non-compaction (LVNC) Unlikely primary LVNC but likely represents disease progression Utilize late gadolinium enhancement for myocardial fibrosis/scar Fibrosis in DMD is sub-epicardial and subendocardial in ischemic cardiomyopathy Left ventricular mechanics Myocardial tagging for myocardial strain analysis....
26 MRI delayed enhancement and fibrosis MRI short axis view of the left ventricle utilizing Gadolinium delayed enhancement A. DMD 9 year old normal diastolic and systolic function and no fibrosis B. Dystrophinopathy extensive ring of subepimyocardial or midwall fibrosis (arrow) C. Subendomyocardial fibrosis (arrows) associated with ischemic heart disease.... (A. performed at CCHMC; B. Heart, 2004; C. JACC, 2005)
27 6. What signs and symptoms should I watch for? Know your sons baseline Learn to take his pulse At rest While busy Sleeping Buy a stethoscope Develop a relationship with your care provider before you need them
28 6. What signs and symptoms should I watch for? Heart failure symptoms often are difficult to identify in DMD patient Rapid weight gain (or loss) Swelling of feet or overall puffiness Heart racing/skipping beats or fainting (syncope) Chest pain (common) Usually musculoskeletal Coronary occlusion Myocarditis Check cardiac enzymes consider additional imaging
29 7. What treatment is available? Currently, standard HF treatment Taken from adult HF experience Treatment Not based on pediatric data Not dystrophin specific Goals: Improve survival Slow disease Alleviate symptoms....
30 7. What treatment is available? Standard HF drugs ACE inhibitors enalapril, lisinopril, perindopril Angiotensin- receptor blockers Losartan β-blockers metoprolol, carvedilol Diuretics furosemide, thiazides Aldosterone receptor antagonists Spironolactone, eplerenone Anti-coagulation Coumadin, Aspirin.... NEJM 2003
31 7. What treatment is available-when to start? We know patient will develop cardiac dysfunction at diagnosis Should cardiac meds be started at dx? No data exists to suggest benefit Families exert significant pressure to do something Start ACE inhibitors when evidence of Left ventricular enlargement Ventricular dysfunction Myocardial fibrosis
32 Do steroids benefit the heart in DMD?....
33 7. What treatment is available? Steroids Started early in disease Use dependent on institution Use dependent on country Has been shown to change the time course of the disease Mechanism unknown More than simply the antiinflammatory effect Side effects Hypertension Obesity Delayed puberty Behavioral problems Short stature
34 Steroid Treatment....
35 7. What treatment is available? At end stage HF Continuous IV milrinone Cardiac Transplantation Few DMD patients transplanted More BMD patients transplanted Problems Limited donor availability Trading one disease for another Quality of life issues
36 7. What treatment is available? Ventricular Assist Devices Cutting edge technology Many devices currently under development Possible benefit for subpopulation of DMD/BMD patients Useful as Bridge to transplantation Destination therapy
37 7. What treatment is available? Pacemakers Cardiac re-synchronization therapy Successful in adult heart failure population Preliminary data suggest DMD population may not be good candidates No evidence of dys-synchrony
38 7. What treatment is available? Always a risk/benefit analysis If there is abnormal function (+/- symptoms) Benefits established Normal function unclear Role for research to answer: when, what agent, what dose, how long? Risks: All drugs have side effects Drugs untested in patients with DMD....
39 8. Should carriers have their hearts checked? Often cardiac disease only manifestation Cardiomyopathy risk increases with age Approximately 350 DMD/BMD carriers age < 16 yrs: all normal age yrs: 6%; yrs: 9%; > 50 yrs: 16% DCM Baseline evaluation as young adult Frequency unclear (? every 5 years) Be aware of symptoms Take care of yourself minimize other CV risks smoking, HTN, cholesterol....
40
41 Conclusions Cardiac evaluation should begin at diagnosis
42 Conclusions Ongoing cardiac follow-up is important and the best way to insure long term cardiac health
43 Conclusions When there is evidence of abnormal function treatment is recommended
44 Conclusions Early treatment prior to onset of dysfunction is unproven and controversial Important to consider risks and benefits
45 Conclusions Need to use common sense AT ALL TIMES
46 Conclusions Maintain an open dialog with all care providers They are working FOR YOU
47 Conclusions YOU AND YOUR FAMILY are the most important members of the health care team
48 THANK YOU
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