CARDIOMYOPATHY IS A SPECIAL ENTITY IN CARDIOLOGY.THIS WAS MY SEMINAR IN FIRST YEAR.HAVE A LOOK AFTER IT.

2. definition Cardiomyopathy is a group of disorders that specifically affect the cardiac muscle. It is distinctive because it does not involve valvular,hypertensive ,congenital disorders. Clinically and hemodynamically distinctive.

3. DILATED CARDIOMYOPATHY Dilated cardiomyopathy

4. Most common cause of clinical syndrome of heart failure

5. BACK GROUND The most common cause of the clinical syndrome of chronic heart failure. Clinical outcome has not changed substantially despite the improvements in the treatment of heart failure. Median survival for men is 1.7 yrs ,women 3.2 yrs.---mortality is high. It might be secondary to ischemia, valvular , hypertensive or primary – genetic ,nongenetic ,acquired . It is defined as a ventricular chamber exhibiting increased diastolic and systolic volumes and a low < 45% ejection fraction.

6. Anatomical specimen

7. Natural history of clinical syndrome of heart failure depends on the course of myocardial failure. Most powerful single predictor of outcome is the degree of LV dysfunction as assessed by the LV ejection fraction. Improvement in natural history of heart failure is by improving intrinsic ventricular function. Adverse effect on outcome with impaired intrinsic function.

8. Classification 1995-WHO/ISFC Based on global anatomic description of chamber dimension in systole and diastole. Mixed- DCM,RCM Genetic –HOCM ,ARVD,ARVC Acquired –peripartum,tachycardia induced cardiomyopathies. Secondary –beckerduchennecardiomyopathy. Valvular ,hypertensive,ischaemic are excluded. Ischaemic dilated cardiomyopathy related to previous myocardial infarction and the subsequent remodelling process.

9. Molecular mechanisms 3 GENERAL CATEGORIES: A.a single gene defect Lamin a/c gene myosin heavy chain B.Polymorhic variation in modifier genes –reninangiotensin,adrenergic,endothelin. C.Maladaptive regulated expression of completely normal genes .

10. Gene mutation Cytoskeletal Sarcolemmal Nuclear envelope gene Sarcomere genes Signal pathway genes Ion channels Desmosomal genes

11. Polymorphic variation ACE  adrenergic receptors Endothelin type a receptors

12. Altered expression Decreased expression of the  adrenergic receptors MYHC SERCA2 Increased expression of ANP, MYHC,ACE,ENDOTHELIN,BARK

13. IMPRESSION Single gene defect ----pathway---hypertrophy-----late decompensation----ventricular dilation. Mutiple gene mutations associated LIM protein—knock out mice—decreased systolic,diastolic,b adrenergic pathway Over expression of 3,2,1,2---myocyte hypertrophy, increased fibrosis, apoptosis, L.V dilation.

14. ACE-DD,homozygous for the deletion variant--circulating cardiac ACE activity DD genotype—early remodelling after MI,development of end stage ischaemic dilated cardiomyopathy.

15. DCM AD—56% AR—16% X LINKED -10% AD with skeletal—7.7% AD with conduction defects—2.6% AR with retinitis pigmentosa AR with wooly hair X Mitochondrial DCM

16. DIFFERENT RESPONSE TO MEDICATION ACE DD– worse prognosis Only to beta blockers they are respondent 1 receptor gene—isoproterenol,bucindolol

17. Pathophysiology Progressive myocardial failure is most likely caused by myocardial cell loss than by increased load ischemia.

18. POSSIBLE MECHAnisms for stabilization Increased heart rate and contractility -increased  adrenergic signaling —within seconds. Volume expansion— frank starling—stroke volume---hours Increased contractility –cardiuacmyocyte hypertrophy—days Chronic continued activation of RAS,ANS – progressive myocardial dysfunction RAS ,ACE inhibitors blockers—reverse remodelling,progressive systolic dysfunction

19. process Virtualy all dilated cardiomyiopathies----progressive dilation—myocardial dysfunction in viable segments.—change in chamber shape—less elipitical ,more round. Dilated phenotype—commonest form Ischaemic Following MI Hypertensive Valvular

20. Clinical features Pulsusalternans Pulsustardus Systolic blood pressure normal or less than normal. Raised JVP Prominent a and v waves tricuspid regurgitation b/l basal crepts Pedal edema Hepatomegaly Gallop rhythm Systolic murmurs—Mitral,tricuspid reg.

21. ecg Sinus tachycardia in presence of heart failure. Atrial and ventricular tachyarryhthmias Poor r wave progression Anterior q waves Intaventricular conduction defects –mostly LBBB Left atrial abnormality Hypertensive changes by voltage criteria not evident ST –T changes are seen.

22. 2d echo Dilated chambers Left atrium is usualy enlarged Left ventricle is enlarged.normal 3.8—5.0cm Mitral and tricuspid regurgitation on doppler flow. Stress testing --tachyarryhthmias Dobutamine stress echo helpful in assessing the clinical prognosis.

23. normal

26. NORMAL

27. 2d echo finding m mode

28. Parasternal longitudinal view

29. NORMAL

30. Short axis view m mode

32. Chest x ray pa view

33. Massive cardiomegalywater bottle shaped heart

34. Ischaemiccardiomyopathy

35. Ischaemiccardiomyopathy h/o of MI Clinically significant >70% narrowing of a major epicardialartery,CAD. Degree of myocardial dysfuntion and VD, is not explained solely by previous infarction. An ischaemicDCMis present when a post MI patient left ventrricle experiences remodelling and a drop in ejection fraction. Dilation of LV—15-40%. < 12 months of acute MI. Less number in inferior MI .

36. CONT.. Transmural,subendocardialscarrinng—represents old MI—50% of LV chambers. Worse prognosis—because of ischaemic events Treatment— ACE, B blockers in symptomatic, Diuretics- vol. overload, Spironolactone –advanced, Digoxin is drug choice, Biventricular pacing—plus ICDs—IVCDS, Anticoagulation, Amiodarone, Potassium levels high level normal –4.3-5.0, Digoxin <1.0 ng/ml .

37. Hypertensive cardiomyopathy Systolic function is depressed out of proportion to the increase in wall stress. Not in a patient with hypertensive crisis—unless Ven.dilation and depressed ventricular function remained after correction of hypertension. Major risk factor Increased systolic wall stress. A.No increased wall thickness B.Concentric hypertrophy C.Systolic dysfunction

39. Hypertensive cardiomyopathy

40. CONT.. Prognosis is better in absence of other co morbid conditions ,in whom after load is controlled Treatment— afterloadvigourosly Amlodipine Hydralazine Nitrates blockers

41. Valvularcardiomyopathy Abnormal valve MR.,AR,AS ……….never with severe pure MS. Eccentric hypertrophy—inc. dias stress…MR Aortic regurgitation—both sys and dias AS- conc hyper. After MVR,AVR – if preoperatively mild LVD. Variable prognosis Time of cardiac surgery . Not in MR with LVEF-- <25%. Treatment-surgical,cathetervalvuloplasty. Medical– severeLVD

43. AMLODIPINE is another option for after load reduction –AR—ca blocker -- improved survival

44. Idiopathic dcm

45. idiopathic

46. Idiopathic DCM It is by exclusion. Relatively common. 0.04%. Increases with age. M>F. Myocardial cell hypertrophy,interstitial cell fibrosis Etiology as Alcohol >80g/day-M,>40g/day-F-5 years. HTN160/100 ,uncontrolled Assess TSH levels biopsy

47. pathophysiology 35-50% are familial CARVAJAL syndrome—DCM,woolyhair,keratoderma. Altered signal transduction—phospholamban gene Tafazzin gene—acyltransferase,mitochondrialmem.protein. High mortality and morbidity—lamin A/C gene Post mortem—dilation of the chambers Weight of heart is increased No inc in wall thickness Visible scars Mural endocardial plaque

48. microscopy Myocyte hypertrophy Very large nuclei Increased interstitial fibrosis Myocyte atrophy Inc. cell length individually Ultrastructure– t tubular dilation No adjacent myocyte damage with lymphocyte infiltration—dd– myocarditis. HLA—B27,A2,DR4,DQ4 HLA DRW6 Adenovirus,herpes

49. prognosis Better than ischaemic 50% survival ->5 yrs without ACE LAMIN A/C gene—worse prognosis Treatment NO issue of revascularization Increased incidence of thromboembolic complications B blockers are more useful—viable myocardium All should receive B BLOCKERS unless contraindicated.

50. Anthracyclinecardiomyopathy Doxorubicin.daunorubicin Dose related Dilated >450mg/m2 with no risk factors. Prior mediastinal radiation is a risk factor. Definitive diagnosis is by biopsy Cell vacuolization 16-25% of sampled cells in biopsy Presenting late is better prognosis Carvedilol –beneficiary effect

51. Post partum cardiomyopathy

52. Post partum cardiomyopathy Last trimester < 6 months of delivery Not common Dilated category Better prognosis Recover completely in 50% cases. Family planning counselling should never become pregnant even if full recover of myocardial function present Treatment is aggressive.

54. Alcohol cardiomyopathy Relatively high cardiac output for differentiation. Not good candidates for cardiac transplantation.

55. Chagascardiomyopathy MC cause of NICM . T. cruzi. Triatoma or kissing bug. Blood transfusions. Initial myocarditis in childhood. Recovery—DCM after 30 years. Clinically diagnosed. BBB—HEMIBLOCKS. LVH. Doppler tissue imaging. Mononuclear infiltrates. Apical aneurysm. Ab cross react with myosin. Prognosis-50%. Death—arrhtyhmias. Verapamil,amiodarone,no specific treatment.

56. Trypanosoma,triatoma

57. chagas

58. conclusion 1.Most common cause of clinical syndrome of chronic heart failure. 2.Global anatomic description of chambers in diastole ans systole for classification. 3.Lamin a/c gene –single gene defect – worse prognosis. 4.DCM is mostly familial. 5. 56% AD. 6.ACE DD – worse prognosis,responds to b blocker therapy. 7. Progressive myocardial failure is due to cell loss than by increased ischemia overload.

59. Cont.. 8.RAS ,ACE inhibitors are useful in therapy. 9. All DCM are less ellipitical , more round. 10.Dilated phenotype is commom in cardiomyopathy. 11.Ischaemic after MI ,CAD <12-24 months. 12.Ischemic more worse prognosis than non ischemic. 13.Potassium leels to be maintained high normal in ischemic DCM. 14.Anticoagulation imp. in Isc.DCM. 15.After load to be decreased in htn DCM.

60. CONT.. 16.Amlodipine is good drug in AR. 17.Idiopathic is by exclusion. 18.tafazzin gene is the new gene in pathogenesis of DCM. 19.Lymphocyte infiltration nothing to do with damage of myocardial cells as in myocarditis. 20.no issue of revascularization in idiopathic DCM. 21.higher incidence of thrombotic complications. 22.carvedilol useful in drug induced DCM 23.most common cause of non isc.DCM is chagas.

61. Take home message All should receive beta blockers in DCM unless contraindicated. Anti thrombotic drugs to be started in the treatment of cardiomyopathy Amlodipine in case of AR useful. Alcoholic patients are not good for cardiac transplantation. Medical treatment in case of severe LVD in case of valvular DCM.

62. NEAR FUTURE in management of heart failure AQUARETICS ADENOSINE RECEPTOR ANTAGONISTS MYOSIN ACTIVATORS NOVEL NATRIURETIC PEPTIDES DEVICE THERAPY

63. Management of heart failure is ………

64. Goal of management of heart failure

65. THE FOUR BLESSED LOOKS LOOK BACK AND GET EXPERIENCE LOOK FORWARD AND SEE FUTURE LOOK AROUND AND FIND TRUTH LOOK WITHIN AND FIND CONFIDENCE

66. references HURST CARDIOLOGY HARRISONS 17 thed Internet

67. sites www.heartfailurematters.org

68. THANK YOU Dr.PRAVEEN NAGULA