Heart transplantation pathophysiology

The pathogenesis leading to a cardiac transplant involves the mechanisms leading up to heart failure. Heart failure leads to an inadequate output of the heart to meet the metabolic demands of the body. Features of chronic heart failure like biventricular hypertrophy, four-chamber dilatation, fibrotic scars, myofibrillar loss, sarcoplasmic vacuolation, interstitial fibrosis may be seen in the diseased heart. Post-transplantation changes indicating acute or chronic rejection may be seen. Non-rejection changes include coronary artery disease (eccentric), Quilty effect, interstitial fibrosis, nodular lymphocytic endomyocardial infiltrates, and posttransplant lymphoproliferative disorder in the transplanted heart.

Cardiac Transplantation is the treatment for patients with intractable heart failure, not amenable to medical and device therapy.

• Heart failure results when there is an inadequate output of the heart to meet the metabolic demands of the body. Heart failure can be caused by abnormal function of any part of the heart like the pericardium, the myocardium, the endocardium, the heart valves and the great vessels- the aorta and pulmonary artery.
• Heart failure is characterized by decreased cardiac output but not necessarily decreased ejection fraction.
• Symptoms of heart failure are due to a lack of both forward blood flow to the body, and backward flow into the lungs. The body tries to compensate for the low cardiac output by mechanisms that increase the preload and afterload. These mechanisms lead to exacerbation of the cardiac malfunction and symptoms associated with heart failure.

It is understood that heart failure is the end result of many causes- Common causes whose pathogenesis results in the need for cardiac transplantation may include:^[1]

• Systolic Heart Failure with a low Left Ventricular Ejection Fraction( <35%) may be caused by
  • Ischemic cardiomyopathy
  • Dilated cardiomyopathy
  • Valvular heart disease
  • Hypertensive heart disease
• Ischemic Coronary Artery Disease with Refractory Angina
• Long-standing Intractable life-threatening Arrhythmias
  • Ventricular arrhythmias
• Cardiomyopathies
  • Restrictive and Hypertrophic Cardiomyopathies
  • Non-dilated cardiomyopathies
• Congenital Heart Disease
  • Many congenital heart defects that are not amenable to surgery lead to New York Heart Association functional class IV Heart Failure

On gross pathology, features of chronic heart failure are seen-

• Biventricular hypertrophy
• Moderate to severe four-chamber dilatation are characteristic findings
• Remnant fibrotic scars from previous myocardial infarctions- transmural or subendocardial
• Mural thrombus– most commonly in the left ventricle but may be present in any chamber ^{[2] [3]}

On gross pathology, features of acute or chronic rejection may be seen, if the patient is not on adequate immunosuppressive therapy. ^[3]

• Hypertrophy of myocytes
• Myofibrillar loss
• Sarcoplasmic vacuolation
• Interstitial fibrosis
• Deposition of collagen, mostly in the subendocardial region.
• Variable degree of myocarditis^[3]

Features of mild acute rejection include ^[4]–

• Focal mononuclear cells infiltrate, without the involvement of adjacent myocytes.^[5]

Features of moderate acute rejection include-

• Dense collection of inflammatory cells, associated with involvement of adjacent myocytes.
• Eosinophils and also mononuclear cells are also seen in the infiltrate. ^[5]

Features of severe acute rejection additionally include-

• Hemorrhage
• Edema
• Vasculitis
• Neutrophilic infiltrate ^[2]

Features of chronic rejection include-

• Concentric intimal thickening
• Reservation of internal elastic lamina

• Coronary Artery Disease- Arteriosclerosis- concentric intimal thickening associated with endovasculitis. This is to be compared with ordinary atherosclerosis where lipids are deposited mainly in the endothelium and subendothelium in an eccentric pattern.
• Other changes like- ^[3]
  • Ischemic changes
  • Interstitial fibrosis
  • Mycoytes- hypertrophy, calcification
  • Nodular lymphocytic endomyocardial infiltrates- Seen with the use of Cyclosporin, known as Quilty effect ^[6]
  • Posttransplant lymphoproliferative disorder- Similar to large cell lymphoma

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