Cardiomyopathy, End-stage Heart Disease & Transplantation

1. Cardiomyopathy, End-stage Heart Disease & Transplantation Seoul National University Hospital Department of Thoracic & Cardiovascular Surgery

2. Hypertrophic Cardiomyopathy

3. Hypertrophic Cardiomyopathy • Definition • A myocardial disease characterized by left and/or right ventricular hypertrophy that is usually asymmetric and is associated with microscopic evidence of myocardial fiber disarray. Degree of hypertrophy at any given site can vary substantially & influences clinical manifestations. • Ventricular septal hypertrophy is the most common type of asymmetric hypertrophy, with midventricular, apical, and other types occurring much less frequently. • Forms interfering with left ventricular emptying, termed hypertrophic obstructive cardiomyopathy or idiopathic hypertrophic subaortic stenosis, are surgical important and variable subaortic obstruction and is associated with abnormal systolic anterior motion. • The more commonly occurring nonobstructive forms are not amenable to surgical treatment except for cardiac transplantation.

4. Hypertrophic Cardiomyopathy • Historical note • Hallopeau & Liouiville ; Pathologic finding compatible with HOCM in 19 century • Schmincke ; Pathologic finding in early 20 century • Davies ; Described family form in 1952 • Brock ; Surgical report for diffuse muscular subaortic stenosis • Braunwald & Goodwin ; Described respectively idiopathic hypertrophic subaortic stenosis & hypertrophic obstructive cardiomyopathy • Bigellow ; Simple myotomy using an aortic approach in 1966 • Morrow ; Excision of muscle in 1978

5. Coronary Flow Reserve • Determinants of microvascular dysfunction • Narrowing of epicardial coronary arteries • Structural changes (ie, vascular remodeling with reduced lumen to wall ratio) or functional alterations involving neurohumoral factors • Small coronary arterioles may change their diameter as a result of autonomic innervation • Several extravascular mechanisms such as impaired diastolic relaxation, compression of the coronary arteries by high left ventricular filling pressures, and increased force of contraction ("milking").

6. Hypertrophic Cardiomyopathy • Morphogenesis • Hypertrophic cardiomyopathy is recognized a heterogenous sarcomere diseases, and mutations have been described in the beta-myosin heavy chain gene (chromosome 14q11-q12), in cardiac troponin-T( chromosome I ), in alpha-tropomyosin ( chromosome 15q2), and in two other chromosomes.

7. Hypertrophic Cardiomyopathy • Characteristics • Ratio of thickness between septum and posterior wall is 1.3 or more in almost HCM. • ASH tends to lessen or disappear with somatic growth when present in early life in association with congenital heart disease. • Increased wall thickness is mainly caused by increased fibrous tissue, particularly in the ventricular septum. • Foci of disarrayed muscle cells are interspersed and also abnormalities in orientation of myofibrils. • The LV cavity is small and has a S or sigmoid shape in systole. • Rarely, LV cavity may become dilated in the late stages of HOCM.

8. Hypertrophic Cardiomyopathy • Etiology • HCM is a genetically determined disorder of cardiac muscle transmitted as an autosomal dominant trait, although nonfamilial cases probably occur as well. • HCM can present at any age from early infancy to the sixth or seventh decade. • Echocardiographic studies of patients with HCM, including those with isolated ASH suggest that obstruction is present in only about 20%. • It is uncertain whether isolated ASH, an asymptomatic disease, develops into obstructive cardiomyopathy.

9. Hypertrophic Cardiomyopathy • Natural history • The natural history of HCM is typically variable. • Progression of disease is more rapid in children and young adults • Symptomatic infants and young children represent the more severe end of spectrum. • Annual mortality of HCM has ranged 4-6% in children, and 3-4% in adults. • Sudden cardiac death is common and the risk factors are young age, syncope, family history of malignancy, myocardial ischemia, sustained VT, degree of outflow obstruction.

10. Hypertrophic Cardiomyopathy • Morphology Muscular hypertrophy present in HCM involves the interventricular septum and left ventricle, and id variable in its location and severity • Ventricular septum • Dynamic morphology of septum and mitral valve • Left ventricular free wall • Left ventricular cavity • Histopathology of left ventricle • Left atrium • Mitral valve • Right ventricle • Coronary arteries • Associated lesions

11. Hypertrophic Cardiomyopathy • Clinical features & diagnosis • Symptoms ; angina, DOE, syncope, palpitation • Signs ; late-onset ejection murmur, bifid arterial pulse, palpable left atrial contraction • Ventricular function ; initial diastolic dysfunction • EKG ; LV strain, sometimes Q wave, LVH • Chest radiography ; variable cardiomegaly • Echocardiography & catheterization

12. Hypertrophic Cardiomyopathy • Mitral regurgitation • SAM of the anterior leaflet is a constant features of classic HOCM. • It is likely that severity of mitral regurgitation, magnitude of pressure gradient, and degree of prolongation of LV ejection time are determined by time of onset and duration of mitral leaflet-septal contact. • Mitral regurgitation occurs independent of SAM in about 20% of patients with HOCM. • It can result from mitral valve prolapse, chordal rupture, anomalous attachment of a papillary muscle, anterior leaflet fibrosis, congenital abnormalities, rheumatic disease, or annular calcification

13. Systolic Anterior Motion • The mechanism of SAM is probably multifactorial, most likely, secondary to forward (anterior) displacement of the elongated mitral valve relative to the septum during systole. • The Ventury effect of the high-velocity stream of blood carries the protruding edge of anterior leaflet toward the aortic annulus in early systole • SAM is absent in the nonobstructive HCM • SAN can occur in TGA with IVS • SAM may also appear after inserting a rigid mitral anuloplasty ring

14. Systolic Anterior MotionProposed Mechanism A ; Coaptation point( arrow ) is in the body of anterior and posterior leaflets. B & C ; Anterior and basal movement of the residual length of the anterior leaflet with septal contact and failure of leaflet coaptation & subsequent mitral regurgitation

15. Technique of Operation • Myectomy by aortic approach • Adjunts to conventional myectomy • Extended myectomy & reconstruction of subvalvular mitral apparatus • Plication of anterior leaflet with myectomy • Ventriculotomy with transaortic approach • Modified Konno operation • Mitral valve replacement

16. Hypertrophic Cardiomyopathy • Postoperative care • LAP of 16-18 mmHg required early postoperatively for adequate volume • Digitalis, beta-receptor agonist should be avoided • Hypovolemia and nitroglycerin, which can reduce LV volume and exaggerate any residual gradient, should be avoided. • Atrial fibrillation may be poorly tolerated • This can be best accomplished by use of beta-adrenergic receptor blocking agents ( propranolol ), calcium antagonists ( verapamil, diltiazem ), or amiodarone

17. Results of Operation • Early death • Time-related survival • Mode of death • Incremental risk factors • Myocardial metabolic changes • Conduction disturbance • Perioperative myocardial infarction • Iatrogenic defects • Postoperative pressure gradients • Mitral regurgitation • Left ventricular aneurysm • Symptomatic status • Left ventricular function

18. Postoperative Aortic Regurgitation • Causes after operation for HOCM • Small aortic annulus probably by increased operative difficulty & increased retraction & possible injury of aortic valve cusp • Loss of support of right coronary cusp as a result of excising septal muscle beneath it may result in aortic regurgitation as may altered velocity, direction, and dynamics of the turbulent jet of blood in the outflow tract

19. Incremental Risk Factors • Preoperative syncope • Increased NYHA functional class • Documented coronary artery disease • Concomitant procedures • Mitral valve replacement • Development of complete heart block • Outflow tract gradients greater than 15mmHg were incremental risk factors for late death

20. Hypertrophic Cardiomyopathy • Indications for operation • Symptomatic patients after appropriate medical therapy, pacemaker therapy, or septal ablation and who has LVOT gradient at rest more than 50mmHg • Symptomatic patients with small gradient at rest but in whom a gradient of 50mmHg or greater on provocation, after ectopic beat, or after cessation of exercise • Occurrence of atrial fibrillation is also an indication • Less symptomatic patients with severe gradients, with MR, history of syncope, asymptmatic young patients with gradients more than 100mmHg

21. Hypertrophic Cardiomyopathy Special situations & controversies • Alterative therapy • Left ventricular-aortic conduit • Dual-chamber pacing • Percutaneous transluminal septal myocardial ablation • Cardioverter-defibrillator • Cardiac transplantation

22. Heart Failure

23. Heart Failure • Definition • A clinical syndrome that represents a complication or common final pathway of many heart diseases in which defective cardiac filling( diastolic heart failure ) or impaired contraction( systolic heart failure ) or emptying results in the heart’s ability to pump a sufficient amount of blood to support tissue metabolism, or to be able to do so only with elevated filling pressure. • It is commonly characterized by secondary organ abnormalities in the skeletal muscles( fatigue ), lungs( dyspnea ), and kidneys( salt & fluid retention )

24. Heart Failure • Pathophysiology • Cardiorenal mechanism • Hemodynamic mechanisms • Neurohumoral mechanisms • Myocardial hypertrophy & ventricular remodeling mechanisms • Other factors

25. Mechanisms of Remodeling • Transition from compensatory hypertrophy to heart failure is related to alterations in cell organization and changes in coronary blood flow to the increased cell mass of the hypertrophied ventricle. • Alterations in myocyte biology include excitation-contraction coupling, myosin heavy chain or fetal gene expression, beta-adrenergic desensitization. • Alteration in the extracellular matrix of the myocardium include replacement fibrosis. • Changes in configuration of the ventricular chamber include dilation, change in shape( increased sphericity), thinning of wall and regurgitation.

26. Heart Failure • Clinical features & diagnostic criteria • Stage A ; patient at high risk for developing heart failure but has no structural disorder of the heart • Stage B ; patient with structural disorder of the heart but has never developed symptoms of heart failure • Stage C ; patient with past or current symptoms of heart failure associated with underlying structural heart disease • Stage D ; patient with end-stage disease

27. Heart Failure • Natural history • About 3% of the adult population is treated for heart failure and occurrence of heart failure increases with age so that 6% to 10% of people older than 65 years have heart failure • Heart failure accounts about 5-10% of all hospital admissions. • Heart failure results in nearly 300,000 deaths per year in the United States, 60% sudden. • Sudden death may be completely unexpected(1/3), a consequence of worsening heart failure(1/3), or a result of progression of heart failure alone(1/3)

28. Cardiomyopathy • Definition • A cardiac muscle disease process that leads to clinical myocardial dysfunction • The disease process results in morphologic changes in the heart that are typically classified as (1) dilated cardiomyopathy, (2) hypertrophic cardiomyopathy, (3) restrictive cardiomyopathy, and (4) arrhythmogenic right ventricular dysplasia

29. Dilated Cardiomyopathy • Definition • A cardiac muscle disease characterized by dilatation of one or both ventricles and impairment of at least systolic function. Dilated cardiomyopathy may be considered the final outcome of pathways produced by a variety of agents of myocardial insult • These include selenium deficiency , alcohol, smoking, and a variety of viral agents and in some patients, the causative factor may be immune, genetic, or familial. • In many patients, none of these can be identified, & the condition is termed idiopathic dilated cardiomyopathy

30. Dilated Cardiomyopathy • Morphology • Enlargement (increased volume) of ventricles and, to a lesser extent, the atria • Variable degree of hypertrophy is often present • Extensive interstitial & perivascular fibrosis, occasionally calcification, in the ventricular myocardium in microscopic examination • Myocardial cell degeneration is usually seen • The specific diagnosis of DCM usually cannot be made by endocardial biopsy

31. Dilated Cardiomyopathy • Clinical features & diagnosis • DCM frequently is of unknown etiology • Speculation as to possible progression of infective, particularly viral, myocarditis to full-blown dilated cardiomyopathy, particularly frequent in children • Alcoholism, pregnancy, and systemic hypertension may provide a background for its development • About 25% of patients have familiar disease (X-linked) • Characterized by impaired systolic function, but in late, decreased left ventricular compliance may develop • Al forms of cardiomyopathy may have a nonspecific prodromal phase, lasting weeks or months

32. Dilated Cardiomyopathy • Natural history • DCM is a serious disease, and about 80% of patients are dead within 10 years of its evident onset • The course is variable, with some patients dying within 1 to 2 years and a few having more fulminating course • Cardiac antibodies play a functional role and their removal may induce hemodynamic improvement • A few patients with dilated cardiomyopathy recover spontaneously. • Mode of death is usually chronic cardiac failure, or occasionally intractable arrhythmias, and sometimes sudden

33. Dilated Cardiomyopathy • Risk factors for death • Marked cardiomegaly • Cardiac rhythm other than sinus, especially ventricular arrhythmia • Pulmonary hypertension • Elevated right atrial pressure • Thromboembolism in great LV with atrial fibrillation

34. Restrictive Cardiomyopathy • Definition • A cardiac muscle disease that results in impaired diastolic function with loss of compliance • Morphology • Characterized by diffuse ventricular hypertrophy. The ventricular walls are excessively rigid, resulting in restrictive filling and reduced volume of ventricle with normal or near normal systolic function. Microscopically, fibrosis and hypertrophy of myocytes are usually apparent.

35. Restrictive Cardiomyopathy • Clinical features & diagnosis • Restrictive cardiomyopathy may be secondary to • amyloid infiltration and other process, with or • without eosinophilia. In number of cases the • etiology is unknown • This condition simulates chronic constrictive • pericarditis with severe impairment of compliance • Generally, symptoms are of long duration, & death • is delayed for 5 to 20 years after abnormalities of • cardiac function and not well defined

36. Endomyocardial Fibroelastosis • Definition • A form of restrictive cardiomyopathy with unknown etiology in which the pathologic process is restricted to the endocardium • Morphology • Fibrous endocardial lesions involving primarily the inflow portions of right and left ventricles • The outflow of the ventricle is usually spared. • Both ventricles are commonly involved, but 40% purely in LV and 10% in RV involvement • A thick layer of hyalinized fibrous tissue, calcification in endocardium and sparsity of elastic fiber • Possible role of diet in banana, malnutrition, and various infections as well as an immunologic response

37. Endomyocardial Fibroelastosis • Clinical features & diagnosis • As progressively increasing endomyocardial fibrosis develops, with consequent restriction of ventricular filling, ventricular end-diastolic pressure elevate as do pulmonary or systemic venous pressure, depending on which ventricle is involved • Involvement of AV valves then adds valvar regurgitation to the already impaired hemodynamic state • Endomyocardial fibrosis(or obliterative cardiomyopath ) tends to affect children and young adults with. It occurs primarily in Uganda, Nigeria, and India. • This type of cardiomyopathy is generally unfavorable, slowly deteriorating course and death within 5 to 10 years, often within 1 to 2 years.

38. Secondary Cardiomyopathies • Associated with cardiac or systemic disorders Ischemic Valvar Hypertensive Inflammatory - Myocarditis, Chanas disease, HIV Metabolic – Thyrotoxicosis, Hypothyroidism, Storage diseases Systemic diseases - Systemic lupus erthematosus, Sarcoidosis Muscular dystrophies - Duchenne’s, Becker-type Neuromuscular disorders - Friedreich’s ataxia Sensitivity and toxic reactions – Alcohol, Radiation, Anthracyclines Peripartum (pregnancy)

39. Treatment of Heart Failure

40. Therapy for Heart Failure • Non-drug therapy • Dietary sodium restriction • Exercise training • Treatments of no benefit or harm • Calcium-channel blockers • Positive inotropic therapy

41. Heart Failure • Drug therapy • Angiotensin-converting enzyme inhibitors, ACE1 Enalpril 10mg bid • Angiotensin-receptor blocker, RBs Losartan 50mg, captopril • Beta-blocker ; Carvedilol, metoprolol, bisoprolol • Aldosterone receptor-blocker Spironolactone 25~50mg/day • Vasodilator ; Hydralazine & isosorbide dinitrate • Digoxin • Diuretics • Antiplatelet therapy & anticoagulation

42. End-Stage Heart Disease • Surgical Options 1. Ventricular assist device 2. Dynamic cardiomyoplasty 3. Ventricular volume reduction 4. Heart transplantation

43. Treatment of Dilated Ventricle • Options to Reserve Compensatory Mechanism 1. Increase the LV mass (cardiomyoplasty) 2. Decrease the wall tension (vasodilator) 3. Reduce the LV radius (cardioreduction)

44. Myocardial Infarction • Sequence • Acute & chronic inflammatory reaction after infarction and myocardial fibrosis • Ventricular pressure stretches & thins the healing area including ventricular dilation. • The dilated heart may result in congestive heart failure. • Ventricular aneurysm may form, further compromising heart function.

45. Ischemic Cardiomyopathy • Ventricular Reconstruction • Recommended in patients with coronary disease as a treatment for heart failure, angina, and thromboembolic complications or to control ventricular arrhythmias • Technical modifications • Purse-string technique • Endoaneurysmorrhaphy technique • Endoventricular circuloplasty

46. Volume Reduction Surgery 1. Selection • 1) Dilated cardiomyopathy (LVEDD>70mm) • 2) Contraindication to transplantation • 3) Hemodynamic deterioration waiting • transplantation 2. Exclusion • 1) Ischemic cardiomyopathy • 2) Cardiac fibrosis • 3) Active myocarditis

47. Heart Reduction Surgery • Cardiac Function after Reduction 1. Increases in end-systolic elastance & preload recruitable stroke work, and ejection fraction due to decrease in LVEDV with no little change in stroke volume. 2. Decreases in LVEDV and increases in diastolic chamber stiffness. 3. At any ventricular pressure, mass reduction results in a decrease in ventricular wall stress. • (reduction of myocardial afterload, and subendocardial ischemia)

48. Dor Procedure • Pathophysiology • Relieve ischemia by revascularization • Diminish ventricular volume • Restore the ventricle to more normal geometry • Further diminishes volume overload by mitral valve repair when appropriate

49. Overlapping Ventriculoplasty • Schema of integrated overlapping ventriculoplasty with PMP

50. Septal Aneurysm Patch Exclusion A, Apical aneurysm with significant thinning and aneurysmal involvement of distal septum. B, Pericardial patch sewn to the preserved normal portion of the septum on three sides. C, The patch effectively excludes the aneurysmal portion of the septum