Heart Transplantation in Cardiac Amyloidosis: When to Consider It?
Table of Contents
Introduction
Cardiac amyloidosis (CA) is among the most difficult infiltrative cardiomyopathies, with misfolded amyloid proteins accumulating in the heart tissue and causing progressive diastolic and subsequently systolic dysfunction. With the improvement of early diagnosis and treatment, survival has become better, but advanced disease eventually may be left with no choice but heart transplantation (HTx).
In this detailed article, we will discuss when heart transplant should be considered in cardiac amyloidosis, with an emphasis on clinical indications, patient selection, results, challenges, and future directions.
1. Cardiac Amyloidosis: Understanding
- Definition: Cardiac amyloidosis is due to extracellular deposition of amyloid fibrils within myocardial tissue.
- Types relevant to CA:
- AL amyloidosis (light-chain amyloidosis)
- ATTR amyloidosis (hereditary and wild-type transthyretin)
- Effect on the heart:
- Restrictive cardiomyopathy
- Heart failure with preserved ejection fraction (HFpEF) in early stages
- Conduction disturbances and arrhythmias
- Advanced systolic heart failure in later stages
2. Current Treatment Options Before Transplantation
- For AL Amyloidosis:
- Chemotherapy (bortezomib, melphalan, dexamethasone)
- Autologous stem cell transplantation (ASCT) in selected patients
- For ATTR Amyloidosis:
- Tafamidis (stabilizer of transthyretin)
- Gene silencing therapies (patisiran, inotersen, vutrisiran)
- Supportive cardiac management:
- Diuretics in the setting of congestion
- Beta-blocker and ACE inhibitor use cautiously
- Anticoagulation in atrial fibrillation
Even with these therapies, patients who have progressive end-stage heart failure will require heart transplantation.
3. When to Consider Heart Transplantation in CA?
Heart transplant is not the first-line treatment for cardiac amyloidosis but may be considered in carefully selected patients.
Key Indications:
- Younger patients (usually < 65 years, though cut-offs for age vary)
- Advanced heart failure (NYHA class III–IV)
- Severe diastolic/systolic dysfunction unresponsive to medical therapy
- Single-organ involvement (dominant or isolated cardiac disease)
- Deep hematologic response (in AL amyloidosis patients in remission with chemotherapy)
- Lack of major extra-cardiac organ involvement (renal, hepatic, neurological) that might jeopardize outcomes
4. Patient Selection Criteria
For AL Amyloidosis:
- Should have achieved hematologic response (to prevent recurrence in the transplanted heart)
- No extensive renal or liver involvement
- Age and comorbidities evaluated thoroughly
For ATTR Amyloidosis:
- Potentially better transplant recipients, particularly hereditary type
- Gene therapies can be continued after transplant
- Generally less systemic organ involvement than AL type
Absolute Contraindications:
- Multi-organ amyloid deposition with severe dysfunction
- Active refractory amyloid production
- Advanced frailty
5. Challenges in Heart Transplantation for CA
- Reoccurrence of amyloid deposition in the new heart in case of failure to attain hematologic control (AL).
- Restricted availability of donor hearts.
- Increased perioperative hazards due to restrictive physiology.
- Multidisciplinary treatment requirement (hematology, cardiology, transplant medicine).
6. Outcomes Following Heart Transplantation
- AL Amyloidosis: Results have considerably improved when used alongside chemotherapy and ASCT. Survival rates at one year now approximate those of non-amyloid cardiomyopathy transplant recipients in selected institutions.
- ATTR Amyloidosis: Good post-transplant survival can be attained by the patients, particularly if systemic progression is managed with disease-modifying drugs.
- Survival Data:
- Post-transplant survival varies from 7–10 years, which is similar to other cardiomyopathies when patients are adequately selected.
- Quality of Life: Marked relief from symptoms, improvement in functional capacity, and independence.
7. Role of Combined Therapies (Sequential Approach)
- AL Amyloidosis: Heart transplant first, followed by autologous stem cell transplant (ASCT), to ablate the underlying plasma cell clone.
- ATTR Amyloidosis: Heart transplant is augmented by tafamidis or gene silencers to inhibit systemic progression.
8. Future Directions in CA and Transplantation
- Better diagnostic tools (cardiac MRI, nuclear imaging) enable earlier detection of transplant candidates.
- New gene therapies for ATTR are revolutionizing the field, slowing disease progression and minimizing the requirement for transplant.
- Ongoing clinical trials could further optimize patient selection and enhance long-term results.
9. Patient Counseling and Support
- Patients should be informed regarding the risks, benefits, and commitment involved with transplantation.
- Psychological counseling is essential.
- Patient support organizations, e.g., amyloidosissupport.in, offer excellent information and help connect patients with transplant programs.
10. Conclusion
Cardiac amyloidosis heart transplantation is a life-saving option in well-referenced patients with dominant cardiac involvement, end-stage heart failure, and well-controlled hematologically.
The choice should always remain multidisciplinary, incorporating cardiologists, hematologists, and transplant teams, for the best possible outcome.