HOCM

one of my first presentations about HOCM

1. Hypertrophic Cardiomyopathy Dr.Dina Abdelsalam,MD lecturer Cardiovascular medicine

2. Agenda: Definition. Pathology. Pathogenesis. Echocardiographic Evaluation Clinical manifestations Natural history Treatment

3. Pathology Macroscopic examination of the myocardium: - the ventricular wall is thickened, preferentially affecting the interventricular septum – even when the hypertrophy is diffuse it is usually asymmetrical, affecting some parts of the myocardium more than others - variants. the ventricular cavity is typically small the mitral valve often has elongated leaflets . Shirani J et. al, JACC 2000

4. Microscopic Focal distribution of myocyte disarray (to the left) adjacent to normal parallel alignment of myocytes ; Adapted from: Varnavaa AM et al., Heart 2000;84:476-482

5. Hypertrophic Cardiomyopathy absence of high blood pressure or valvular stenosis left ventricular cavity usually small ventricular hypertrophy is asymmetric search for a genetic abnormality that might be causing this disease mutation of b -myosin heavy chain, one of the proteins of the myocardial sarcomere

6. Septal to posterior wall thickness 1.3:1 D.D

7. …then click the placeholders to add your own pictures and captions. HOCM variant

8. Pathophysiology - Dynamic left ventricular outflow tract obstruction Mitral regurgitation Diastolic dysfunction Myocardial ischemia Cardiac arrhythmias

9. Assessment of LVOT in HOCM SAM. Aortic notching. Abrupt partial closure in systole.

10. Dynamic left ventricular outflow tract obstruction The original “classic” feature We now know that it is absent in about half of the patients, and the severity of the obstruction varies greatly in those who do have it The causes of obstruction: - Narrowed left ventricular outflow tract due to hypertrophied interventricular septum - Anterior displacement of the mitral valve leaflets during systole ( sam - systolic anterior motion of the mitral valve).

11. Doppler study of LVOT: Late peaking of LVOT gradient: is evidence of the dynamic nature of the gradient that develop mid to late systole rather than being related to fixed obstruction (dagger shape) Prominent presystolic flow in LVOT. Maneuvers to unmask LVOT occult gradient.

12. Dynamic left ventricular outflow tract obstruction The severity of obstruction increases with: - Any maneuver that increases the force of contraction - Any maneuver that decreases filling of the ventricle

13. Dynamic left ventricular outflow tract obstruction The severity of obstruction increases with: - any maneuver that increases the force of contraction  exercise  positive inotropic agents - any maneuver that decreases filling of the ventricle  volume depletion  sudden assumption of upright posture  tachycardia  Valsalva maneuver

14. 2. Mitral regurgitation Non- coaptation of mitral leaflets in systole (at the time when the mitral valve should be closed) due to systolic anterior motion of the anterior mitral leaflet (SAM) Structural abnormalities of the mitral apparatus

15. Mitral regurge : It predominate in mid to late systole during time of Max SAM ,not holosystolic . How to differentiate from LVOT gradient.

16. 3. Diastolic dysfunction The myocardium is stiff, non-compliant The left ventricular diastolic pressure is elevated The filling of the ventricle in diastole is impaired The early diastolic filling phase (when most of the filling occurs under normal conditions) is prolonged and diminished and most of the filling occurs late in ventricular diastole, during the atrial systole Many symptoms are a result of diastolic dysfunction

17. 4. Myocardial ischemia Occurs in the absence significant stenosis of epicardial coronary arteries ( i.E. Coronary angiogram would be “clean”) The mechanisms of ischemia include: -    Supply/demand mismatch due to increased muscle mass - Increased wall tension due to impaired relaxation during diastole -   Abnormal intramyocardial arteries

18. 5. Arrhythmias Paroxysmal supraventricular arrhythmias - occur in 30-50%, result in shorter diastolic filling time; patients have palpitations, shortness of breath, may experience syncope Atrial fibrillation - 15-20%, poorly tolerated – not only is the time for diastolic filling decreased, but patients loose the “atrial kick” Non-sustained ventricular tachycardia - occurs during ambulatory monitoring in 25% of patients

19. 5. Arrhythmias Sustained ventricular tachycardia/ventricular fibrillation – this is the lethal event for many patients with hypertrophic cardiomyopathy – It is more likely to happen during intense physical exertion

20. Clinical manifestations Dyspnea Fatigue Decreased functional capacity Angina pectoris Dizziness Syncope sudden cardiac death No symptoms The severity of symptoms does not necessarily correlate with the severity of outflow obstruction.  

21. Physical exam Systolic murmur best heard between the apex and left sternal border - Increases in intensity with maneuvers that decrease preload ( valsalva , squatting to standing position). - Does not radiate to the carotid arteries Sustained apical impulse S4 Bisferiens pulse (carotids, femoral arteries)  

22. Diagnostic Tests CXR – mostly normal routine blood-work – unremarkable EKG – usually shows marked LVH Echocardiogram – is the diagnostic test of choice

23. Natural history Risk factors for cardiac death: -        Marked ventricular wall hypertrophy (>30mm) -        Young age at presentation (<14 years) -        History of syncope - History of aborted cardiac arrest        family history of sudden cardiac death - Certain genetic mutations sudden cardiac death Progressive heart failure “burnt-out” hypertrophic cardiomyopathy

24. Management -  Careful family history focused on sudden cardiac death -  Exercise testing to determine the presence of exercise-induced LVOT gradient - counseling regarding avoidance of strenuous exercise, avoidance of dehydration - All first-degree family members should be periodically screened with an echocardiogram – yearly between ages 12-18, every 5 years thereafter - Consider genetic testing       

25. Treatment No randomized clinical trials of medical therapy. Three classes of negative- inotropic agents used, often in combination.

26. Treatment Beta-blockers - first-line therapy, clinical improvement >50% - negative inotropic effect decreases outflow gradient decreased myocardial demand results in reduced ischemia prolonged diastolic filling time results in improved LV filling as well as improved coronary perfusion - may have an antiarrhythmic effect please NOTE that in hypertrophic cardiomyopathy , as opposed to dilated cardiomyopathy , we are using beta- blockers for their negative inotropic effect

27. Treatment Calcium-channel blockers useful in patients who do not tolerate beta-blockers, or in combination with beta-blockers Disopyramide may be useful in some patients with a resting gradient due to its strong negative inotropic effects

28. Non-Pharmacological Therapy Surgical septal myectomy in patients that remain symptomatic (dyspnea or angina limiting daily activities) despite maximal medical therapy and have significant resting or provoked outflow gradient the basal interventricular septum is excised which “opens-up” the left ventricular outflow

29. Nishimura, R. A. et al. N Engl J Med 2004;350:1320-1327 Surgical Septal Myectomy

30. Non-Pharmacological Therapy Surgical septal myectomy this procedure has been done since the 1960’s operative mortality is <1-2% most patients will have dramatic improvement in their gradient as well as symptoms complications: complete heart block (3%), VSD (<1%), AR (<1%)

31. Non-Pharmacological Therapy Alcohol-induced septal ablation performed percutaneously in cardiac catheterization laboratory 100% alcohol is injected into a septal perforator - this results in infarction of the injected area

32. Braunwald, E. N Engl J Med 2002;347:1306-1307 Alcohol-Induced Septal Ablation

33. Alcohol-Induced Septal Ablation Adapted from: Hypertrophic Cardiomyopathy, Cleveland Clinic Heart Center, clevelandclinic.org

34. Non-Pharmacological Therapy Alcohol-induced septal ablation the gradient is reduced to <20mm Hg in 70-80% symptom relief is somewhat lower than with surgical myectomy complications: mortality <1-2%, complete heart block (10-30%), VSD, AR, ventricular fibrillation, myocardial infarction of a larger territory

35. Non-pharmacological therapy Dual-chamber pacemaker ventricular depolarization and contraction starting in the rv apex may alter the outflow gradient and reduce symptoms Results of randomized trials have been neutral used in patients with significant symptoms who would not tolerate surgical therapy

36. Non-Pharmacological Therapy Cardiac transplantation reserved for patients who are severely symptomatic despite maximal pharmacological as well as non- pharmacological therapy no significant residual gradient but severe disabling diastolic dysfunction “burnt-out” hypertrophic cardiomyopathy now with systolic dysfunction

37. Prevention of Sudden Cardiac Death Implantable cardioverter-defibrillators indications are evolving considered in patients perceived to be at higher risk for sudden cardiac death additional value of identifying the specific genetic mutation for risk-stratification is being studied and is likely to be used clinically in the near future

38. CAVEATS strenuous exercise, especially isometric, increases the gradient and the probability of hemodynamic collaps /ventricular arrhythmias/sudden cardiac death dehydration, as well as marked peripheral vasodilation can be life-threatening

39. Caveats Atrial fibrillation is poorly tolerated and should be addressed promptly in the setting of increased symptoms and hypotension. The threshold to perform electrical cardioversion should be low Inotropes (dopamine, dobutamine , milrinone ) should be avoided in patients with hypertrophic cardiomyopathy . In a hypotensive patient, fluids and pure vasoconstrictors ( phenylephrine ) are to be used

40. THANKS