Cardiac Transplantation and Prolonged Assisted Circulation¶
Chapter 271 | Part 6: Disorders of the Cardiovascular System
KEY CLINICAL POINTS¶
- Cardiac transplantation has a 1-year survival >80% and median survival of 12.5 years with improved outcomes due to immunosuppression and better management of complications.
- Listing criteria for cardiac transplantation include refractory heart failure with VO <14 mL/kg/min, cardiorenal syndrome, and advanced comorbidities, with age and BMI as relative contraindications.
- Immunosuppression regimens include tacrolimus, mycophenolate mofetil, and prednisone, with emerging roles for IL-2 receptor antagonists and anti-CMV therapies.
- Cardiac allograft vasculopathy (CAV) is a major late complication, with statins and noninvasive testing (e.g., coronary flow reserve) critical for prevention and monitoring.
- Centrifugal-flow LVAS like the HeartMate 3 offer improved survival (median >5 years) and reduced complications compared to older axial-flow devices.
1. DEFINITION & OVERVIEW¶
Cardiac transplantation is a surgical procedure to replace a diseased heart with a donor heart, primarily for advanced heart failure. Prolonged assisted circulation refers to mechanical circulatory support devices (LVAS) used as a bridge to transplant or destination therapy. Outcomes have improved with advancements in immunosuppression and donor management.
Table 271-1 Principles for Listing Candidates for Cardiac Transplantation¶
| PRINCIPLE | COMMENT |
|---|---|
| Advanced disease severity | Refractory heart failure with VO <14 mL/kg/min (or <12 if on beta blockers) or percent predicted VO <50%; cardiorenal syndrome, inotropic therapy, or LVAD dependence |
| Comorbidity | Age is not absolute contraindication, but frailty is relative. BMI >35 requires weight loss. Cancer and diabetes are individualized considerations. eGFR <30 is relative contraindication. |
| Psychosocial issues | Tobacco use must be stopped for 6 months. Substance abuse (including marijuana) is contraindication unless controlled. Cognitive disabilities or dementia are contraindications. |
| Donor-recipient match | Donor weight £30% below recipient (same sex) or £20% (female-to-male). Age typically <55, but often exceeded due to shortages. Size match via predicted heart mass calculator. |
| PRINCIPLE | COMMENT |
|---|---|
| Concomitant pathology | Exclusion of coronary artery disease, left ventricular hypertrophy, or severe allograft injury (excess troponins, poor contractility). |
1.1 Historical Context¶
First successful human-to-human transplant performed by Christiaan Barnard in 1967. Modern techniques include orthotopic transplantation and ex situ reanimation of donor hearts.
1.2 Indications¶
Advanced heart failure refractory to medical therapy, cardiorenal syndrome, and end-organ damage. Criteria include VO <14 mL/kg/min, need for inotropic support, and failed LVAD.
2. EPIDEMIOLOGY¶
Global demand for cardiac transplants exceeds donor availability. Incidence is rising due to aging populations and TTR amyloidosis. Risk factors include advanced age, frailty, and comorbidities like diabetes and renal failure. Survival rates: 1-year >80%, median 12.5 years, conditional survival 14.8 years if first-year survival achieved.
2.1 Demographics¶
Predominantly older adults (age >55), with younger patients for AL amyloidosis. Ethnic disparities in donor availability and allocation.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Cardiac transplantation addresses end-stage heart failure from ischemic or non-ischemic causes. Prolonged assisted circulation relies on mechanical devices to support ventricular function. Key pathophysiology includes immunologic rejection, allograft vasculopathy, and hemocompatibility issues.
3.1 Rejection Mechanisms¶
Acute cellular rejection (ACR): T-cell mediated, lymphocytic infiltrates. Antibody-mediated rejection (AMR): Donor-specific antibodies, complement activation, and vasculitis. CAV: Accelerated coronary artery disease due to immunologic and non-immunologic insults.
3.2 Allograft Vasculopathy¶
Diffuse intimal thickening of coronary arteries, initiated by endothelialitis and ischemia-reperfusion injury. Worsened by hypertension, hyperlipidemia, and glucose dysregulation.
4. CLINICAL FEATURES¶
Symptoms include dyspnea, fatigue, and reduced exercise tolerance. Signs of rejection: fever, arrhythmias, and hemodynamic instability. Complications: CAV, malignancy, renal failure, and device-related thrombosis.
4.1 Late Complications¶
Cardiac allograft vasculopathy (CAV), malignancy (especially post-transplant lymphoproliferative disorders), and renal dysfunction. Neurologic complications from device thrombosis or hemolysis.
5. DIFFERENTIAL DIAGNOSIS¶
Differentiate from other causes of heart failure (e.g., ischemia, valvular disease) and rejection. Consider infections (CMV, Aspergillus), malignancy, and device-related complications.
5.1 Rejection vs. Infection¶
ACR presents with fever, arrhythmias, and hemodynamic instability. Infections (e.g., CMV) may present with similar symptoms but require viral PCR and imaging.
6. INVESTIGATIONS & DIAGNOSIS¶
Endomyocardial biopsy for rejection, coronary angiography for CAV, and noninvasive testing (e.g., coronary flow reserve). Immunological markers (donor-specific antibodies) and hemodynamic monitoring.
Table 271-2 Immunoprophylaxis Drugs in Cardiac Transplantation¶
| DRUG CLASS | GENERIC DRUG | CELLULAR TARGET | MAJOR SIDE EFFECTS |
|---|---|---|---|
| Calcineurin inhibitors | Cyclosporine | Binds to cyclophilin, inhibits calcineurin | Hypertension, dyslipidemia, gum hypertrophy, hypertrichosis |
| Calcineurin inhibitors | Tacrolimus | Binds to FK506 binding protein, inhibits calcine,urin | Hypertension, dyslipidemia, alopecia, diabetes mellitus |
| Antithymocyte globulin (ATG) | Rabbit ATG | T-cell depletion via complement-dependent lysis | Cytokine release syndrome, leukopenia, thrombocytopenia |
| Antithymocyte globulin (ATG) | Horse ATG | Same as above | Same as above |
| Interleukin-2 receptor antagonists | Basiliximab | Inhibits CD-25 of IL-2 receptor | Well tolerated; rare hypersensitivity; increased infection risk with calcineurin inhibitors |
| Antimetabolites | Azathioprine | Imidazolyl derivative of 6-mercaptopurine | Bone marrow suppression, pancreatitis, hepatitis |
| Antimetabolites | Mycophenolate Mofetil | Inhibits inosine monophosphate dehydrogenase | Leukopenia, gastrointestinal toxicity |
| Proliferation signal inhibitors | Sirolimus | Binds FKBP12, inhibits mTOR | Delayed wound healing, pneumonia, pericardial effusion, hyperlipidemia |
| Proliferation signal inhibitors | Everolimus | Binds FKBP12, inhibits mTORC1 | Dyslipidemia, stomatitis, pericardial effusions, pancytopenia |
6.1 Diagnostic Criteria¶
ACR: Lymphocytic infiltrates on biopsy. AMR: Donor-specific antibodies, complement fixation, and vasculitis. CAV: Angiographic evidence of diffuse intimal thickening.
7. MANAGEMENT & TREATMENT¶
Immunosuppression (tacrolimus, mycophenolate, steroids), anti-rejection therapies (plasmapheresis, rituximab), and management of CAV (statins, revascularization). LVAS management includes anticoagulation, infection control, and device optimization.
7.1 Immunosuppression¶
Triple-drug regimen: tacrolimus, mycophenolate mofetil, and prednisone. Induction therapy with basiliximab or ATG for high-risk patients. Monitoring for nephrotoxicity and infections.
7.2 LVAS Management¶
Optimize systemic blood pressure (target ≤ 90 mmHg), manage hemolysis (lactate dehydrogenase monitoring), and prevent infections (driveline care, long-term antibiotics).
8. PROGNOSIS & COMPLICATIONS¶
Median survival 12.5 years, conditional survival 14.8 years. Major complications: CAV (30% at 5 years, 50% at 10 years), infections, malignancy, and device-related thrombosis. Mortality risk for CAV is 50% at 5 years.
8.1 Long-term Outcomes¶
Survival improves with newer LVAS (HeartMate 3: 60% at 5 years). CAV remains the leading cause of late graft failure. Malignancy incidence is 2–3x higher than general population.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Requires multidisciplinary management, with risks of rejection and maternal complications. Pediatrics: LVAS used for congenital heart disease. Elderly: Frailty and comorbidities influence candidacy. Immunosuppression must balance efficacy and infection risk.
9.1 Pregnancy¶
Cardiac transplant recipients can conceive, but require close monitoring for rejection, hypertension, and fetal complications. Anticoagulation and immunosuppression adjustments are critical.
10. KEY POINTS & CLINICAL PEARLS¶
- Cardiac transplantation survival >80% at 1 year, with CAV as the leading late complication. 2. HeartMate 3 LVAS improves survival (median >5 years) and reduces thrombosis. 3. Immunosuppression must balance rejection prevention and infection risk. 4. CAV prevention requires statins and noninvasive coronary flow reserve testing. 5. LVAS complications include hemolysis, infection, and neurologic events from thrombosis.