Heart transplantation in cardiac amyloidosis has evolved from a rarely pursued strategy into an important treatment option for carefully selected patients with advanced heart failure caused by AL or transthyretin cardiac amyloidosis. Historically, clinicians were concerned about systemic disease progression, extracardiac amyloid involvement, recurrent amyloid deposition and poor long-term survival. However, better patient selection and major advances in amyloidosis-specific therapy have substantially changed this landscape (1–5).

Contemporary expert recommendations now support referral of appropriate patients with cardiac amyloidosis and advanced heart failure for specialist transplant evaluation. Importantly, amyloidosis itself should not automatically exclude a patient from consideration. Instead, the decision depends on cardiac disease severity, amyloid type, extracardiac involvement, frailty, nutritional status, comorbidities and the ability to control the underlying amyloid-producing process (1, 2).

The fundamental principle is straightforward: heart transplantation can replace a heart irreversibly damaged by amyloid, but it does not by itself eliminate the systemic disease responsible for amyloid formation. Consequently, successful long-term care requires both transplantation and ongoing amyloidosis-specific management.

Why Can Cardiac Amyloidosis Progress to Advanced Heart Failure?

Cardiac amyloidosis occurs when misfolded proteins accumulate as amyloid fibrils within the extracellular space of the myocardium and other cardiac structures. The two forms responsible for most clinically important cardiac amyloidosis are immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) (11, 12).

As amyloid deposition increases, ventricular walls become progressively infiltrated and stiff. Consequently, ventricular filling becomes impaired and stroke volume may fall even when left ventricular ejection fraction remains relatively preserved. Patients can eventually develop restrictive cardiomyopathy, severe congestion, low cardiac output, atrial and ventricular arrhythmias, conduction disease and progressive functional limitation (2, 11, 12).

Disease-specific treatment can slow or suppress the process responsible for amyloid formation. Nevertheless, treatment cannot always reverse established structural myocardial damage. Therefore, some patients progress to advanced or stage D heart failure despite appropriate amyloidosis-directed treatment and supportive cardiac care.

At that stage, clinicians should consider referral to an advanced heart-failure and transplant program rather than waiting for profound hemodynamic deterioration or irreversible multiorgan failure (1, 2).

When Should Heart Transplantation Be Considered?

No single biomarker, echocardiographic measurement or heart-failure stage automatically determines transplant eligibility. Instead, clinicians examine the patient’s overall trajectory and determine whether cardiac failure has become severe, progressive and insufficiently responsive to medical therapy (1, 2).

Features that may prompt referral for advanced heart-failure assessment include:

• recurrent hospitalization or emergency treatment for heart failure;
• progressive symptoms despite appropriate disease-specific and supportive therapy;
• persistent or recurrent congestion despite diuretic treatment;
• progressive low-output symptoms;
• marked reduction in exercise capacity or functional status;
• progressive hypotension limiting medical treatment;
• worsening renal or hepatic function related to advanced heart failure;
• advanced restrictive or biventricular cardiac dysfunction; and
• a clinical trajectory suggesting poor survival without advanced heart-failure therapy.

Referral does not mean that transplantation will necessarily occur. Instead, it allows specialists to evaluate whether transplantation, combined-organ transplantation, continued medical management or another strategy offers the best balance between expected benefit and risk.

Who May Be Eligible for Heart Transplantation?

Heart-transplant evaluation in amyloidosis combines standard transplant assessment with a detailed evaluation of systemic amyloid disease. This distinction is crucial because replacing the heart cannot reverse severe irreversible disease affecting other organs (1, 2).

Heart Transplantation in AL Amyloidosis

AL cardiac amyloidosis presents a distinctive challenge because the abnormal plasma-cell clone remains capable of producing amyloidogenic immunoglobulin light chains after the diseased heart has been replaced. Therefore, heart transplantation alone does not control AL amyloidosis (1, 10).

Historically, transplant outcomes in AL amyloidosis were disappointing. Patients often had substantial extracardiac disease, and treatment options for suppressing the plasma-cell clone were limited. However, modern plasma-cell therapies and stricter transplant selection have changed this picture substantially (3, 4, 6).

Why Does Hematologic Control Matter?

The goal of AL treatment is to suppress the abnormal plasma-cell clone and reduce production of amyloidogenic light chains. A deep and durable hematologic response therefore improves the likelihood that systemic disease will remain controlled after transplantation.

Whenever possible, the transplant team evaluates whether the plasma-cell disorder can respond effectively to therapy before proceeding. However, severe cardiac failure may itself limit tolerance of intensive hematologic treatment. Profound hypotension, congestion, kidney dysfunction and low cardiac output can make conventional therapy difficult.

For selected patients, clinicians may therefore use a staged strategy in which transplantation first restores cardiac stability, followed by additional plasma-cell–directed therapy. Historically, some programs also used autologous stem-cell transplantation after successful heart transplantation in selected AL patients (5, 10).

What AL Features Can Affect Eligibility?

AL amyloidosis frequently involves several organs. Consequently, clinicians assess more than the severity of cardiomyopathy.

Potential concerns include:

• substantial irreversible kidney disease;
• advanced autonomic or peripheral neuropathy;
• severe gastrointestinal amyloid involvement;
• significant malnutrition or frailty;
• poorly controlled or biologically unfavorable plasma-cell disease;
• significant involvement of other major organs; and
• an overall hematologic prognosis incompatible with meaningful post-transplant survival.

These factors do not operate as a universal checklist. Experienced centers assess them together to determine whether transplantation is likely to provide durable benefit (1, 2).

What Are the Modern Outcomes for AL Heart Transplantation?

Several contemporary studies demonstrate that outcomes have improved substantially.

Kristen and colleagues evaluated 48 patients with cardiac amyloidosis who underwent heart transplantation between 2002 and 2017. The cohort included 32 patients with AL amyloidosis and 16 with hereditary ATTR. In the more contemporary era, transplant survival became comparable with patients transplanted for non-amyloid cardiomyopathy, reflecting changes in patient selection and AL chemotherapy (3).

Griffin and colleagues subsequently compared AL, ATTR and non-amyloid heart-transplant recipients. In the later era of their study, survival after transplantation among selected AL and ATTR patients was comparable with the non-amyloid cohort (4).

More recently, Patel and colleagues reported long-term results in 31 AL patients transplanted between 2009 and 2023. Survival was 87% at one year, 83% at three years, 73% at five years and 67% at eight years. These outcomes were not statistically different from those of non-amyloid heart-transplant recipients at the same center (6).

These studies support transplantation as a viable strategy in selected AL patients. However, they should not be interpreted as evidence that all patients with advanced AL cardiac amyloidosis are transplant candidates. The published cohorts represent carefully selected patients treated at specialized centers.

Heart Transplantation in ATTR Amyloidosis

Heart transplantation can also provide an effective treatment for selected patients with advanced transthyretin amyloid cardiomyopathy. The assessment differs somewhat between wild-type ATTR (ATTRwt) and hereditary or variant ATTR (ATTRv).

ATTRwt Cardiac Amyloidosis

ATTRwt usually develops later in life and often presents with a predominantly cardiac phenotype. Therefore, age-related comorbidities, frailty, kidney function and functional reserve frequently become major determinants of transplant suitability.

Chronological age alone should not replace comprehensive clinical assessment. Nevertheless, advanced age can influence expected long-term benefit and may limit transplant eligibility according to individual transplant-center criteria.

ATTRv Cardiac Amyloidosis

ATTRv requires particularly careful extracardiac assessment because pathogenic TTR variants can produce mixed cardiac and neurologic phenotypes. Patients may have peripheral neuropathy, autonomic dysfunction, gastrointestinal disease or other systemic manifestations in addition to cardiomyopathy (2, 11).

An isolated heart transplant replaces the amyloid-infiltrated heart but leaves the native liver in place. Consequently, variant transthyretin continues to circulate unless disease-specific therapy alters its production or stability. For this reason, clinicians assess the expected trajectory of extracardiac disease when deciding whether isolated heart transplantation offers sufficient long-term benefit.

What Are the Outcomes After Heart Transplantation for ATTR?

Long-term ATTR transplant experience is encouraging in carefully selected patients.

Razvi and colleagues reported outcomes from two tertiary centers in 14 ATTR-CM patients who underwent cardiac transplantation. The cohort included 11 patients with ATTRwt and three with ATTRv. Survival was 100% at one year, 92% at three years and 90% at five years, with the longest survivor followed for more than 19 years (7).

Importantly, the investigators reported no amyloid recurrence in the cardiac allograft during follow-up (7).

Similarly, Vaidya and colleagues reported an overall three-year survival of 81.6% among contemporary cardiac amyloidosis transplant recipients. Three-year survival was 86% among ATTR patients and 69.2% among AL patients, while overall survival did not differ significantly from non-amyloid restrictive cardiomyopathy recipients at the same center (5).

Together, these observations support cardiac transplantation as an effective option for appropriately selected ATTR patients with end-stage cardiomyopathy.

How Do Amyloidosis Transplant Outcomes Compare With Other Heart Transplants?

Large registry analyses provide additional evidence that modern results have improved.

Davis and colleagues analyzed United Network for Organ Sharing data and compared historical and more contemporary eras. Amyloid cardiomyopathy had been associated with substantially worse outcomes in earlier years. However, mortality after transplantation improved markedly in the modern era and approached outcomes among patients transplanted for other forms of restrictive cardiomyopathy (9).

McGoldrick and colleagues later analyzed Organ Procurement and Transplantation Network data from 1999 through 2019. Among 41,103 adult heart-transplant recipients, 425 underwent transplantation for restrictive cardiomyopathy attributed to cardiac amyloidosis. Survival was similar between the amyloidosis and non-restrictive-cardiomyopathy populations at one year (88% versus 89%) and five years (72% versus 77%). However, ten-year survival remained lower in the amyloidosis group (8).

Why Is Extracardiac Amyloidosis So Important?

Extracardiac disease is one of the most important determinants of transplant suitability. A new heart cannot reverse severe systemic damage that has already occurred elsewhere.

Peripheral Neuropathy

Advanced peripheral neuropathy can impair mobility, independence and rehabilitation after surgery. Therefore, clinicians assess neurologic severity and expected progression before transplantation, particularly in ATTRv.

Autonomic Dysfunction

Amyloid-related autonomic dysfunction may cause orthostatic hypotension, gastrointestinal dysmotility and other complications. Severe autonomic disease may persist after cardiac transplantation and complicate postoperative management.

Gastrointestinal Disease

Gastrointestinal amyloidosis can cause diarrhea, early satiety, dysmotility, malabsorption and weight loss. Consequently, severe gastrointestinal involvement can contribute to malnutrition and frailty.

Nutritional Status and Frailty

Nutritional status and functional reserve matter because transplantation requires major surgery followed by intensive rehabilitation and lifelong immunosuppression. Severe frailty or malnutrition may therefore substantially reduce expected benefit.

The Mayo consensus emphasizes systematic assessment of extracardiac manifestations and overall transplant fitness when evaluating cardiac amyloidosis patients (1).

What Role Does Kidney Disease Play?

Kidney dysfunction commonly accompanies advanced cardiac amyloidosis. However, its cause varies. Some patients have intrinsic renal amyloid involvement, whereas others develop cardiorenal dysfunction from reduced cardiac output, venous congestion or diuretic therapy.

This distinction is critical. Hemodynamically mediated renal dysfunction may improve after successful heart transplantation, while severe irreversible structural kidney disease may justify consideration of combined heart–kidney transplantation.

Accordingly, renal assessment may include:

• serial eGFR and creatinine measurements;
• proteinuria and albuminuria assessment;
• history and duration of chronic kidney disease;
• kidney imaging;
• dialysis requirement;
• assessment of hemodynamic contributors; and
• additional nephrologic investigation when the reversibility of renal dysfunction remains uncertain.

When Is Combined-Organ Transplantation Considered?

Some patients have irreversible dysfunction affecting more than one major organ. In selected circumstances, a transplant center may therefore consider combined-organ transplantation rather than isolated heart transplantation.

Combined Heart–Kidney Transplantation

Combined heart–kidney transplantation may be considered when advanced cardiac amyloidosis coexists with severe, irreversible kidney disease that is unlikely to recover after cardiac transplantation.

However, reduced eGFR alone does not automatically justify dual-organ transplantation. The transplant team must distinguish permanent intrinsic renal disease from potentially reversible cardiorenal dysfunction.

Combined Heart–Liver Transplantation

Combined heart–liver transplantation has historically been used in selected hereditary ATTR patients. In principle, the heart transplant replaces the failing cardiac organ while the liver transplant removes the major source of variant transthyretin.

Nevertheless, modern TTR-targeted therapies have changed this strategy substantially. Current decisions about isolated heart versus combined heart–liver transplantation require individualized assessment of TTR genotype, extracardiac phenotype, disease-modifying therapy options and overall transplant benefit (1, 2).

Does ATTR Treatment Continue After Heart Transplantation?

Cardiac transplantation removes the amyloid-infiltrated heart but does not necessarily eliminate systemic ATTR disease. This consideration is especially important in ATTRv patients with peripheral or autonomic neuropathy.

Depending on the patient’s phenotype and residual systemic disease, clinicians may continue or initiate appropriate ATTR-directed therapy after transplantation. The decision should be individualized and coordinated between transplant specialists and the amyloidosis team (1, 2).

Can Mechanical Circulatory Support Be Used in Cardiac Amyloidosis?

Mechanical circulatory support may be more difficult in cardiac amyloidosis than in conventional dilated cardiomyopathy. Many patients have restrictive physiology, relatively small ventricular cavities, biventricular involvement and substantial right ventricular dysfunction (1, 10).

These features can complicate durable left ventricular assist device support. Therefore, mechanical support decisions require individualized assessment at an experienced advanced heart-failure center.

The limitations of durable mechanical support also reinforce the importance of early transplant referral in potentially eligible amyloidosis patients rather than waiting until profound circulatory failure develops.

Can Amyloid Recur in the Transplanted Heart?

Heart transplantation does not biologically cure AL or ATTR amyloidosis. Therefore, continued production of the precursor protein remains possible unless disease-specific therapy adequately controls it.

Nevertheless, clinically important recurrence within the cardiac allograft appears uncommon in carefully selected contemporary cohorts. Vaidya and colleagues reported no amyloid recurrence on endomyocardial biopsy during their follow-up, while the long-term ATTR series by Razvi and colleagues also reported no recurrent amyloid in transplanted hearts (5, 7).

Earlier modern-era experience did document occasional recurrence, emphasizing that long-term disease-specific monitoring remains necessary (9).

What Happens After Heart Transplantation?

Heart transplantation begins a new phase of care rather than ending amyloidosis management. Patients require standard transplant surveillance together with continued monitoring and treatment of the underlying amyloid disease.

Follow-up may include:

• routine cardiac-allograft surveillance;
• immunosuppressive therapy and toxicity monitoring;
• assessment for rejection;
• infection prevention and surveillance;
• renal-function monitoring;
• hematologic monitoring and plasma-cell treatment in AL amyloidosis;
• neurologic and systemic assessment in ATTRv;
• ATTR-directed therapy when clinically appropriate;
• nutritional assessment;
• physical rehabilitation; and
• continued monitoring for extracardiac amyloid progression.

For this reason, long-term follow-up remains multidisciplinary and may involve transplant cardiology, hematology, nephrology, neurology, genetics, nutrition and other specialties according to the patient’s amyloid phenotype.

Why Is Early Referral Important?

Timing can determine whether transplantation remains feasible. Cardiac amyloidosis may progress to hypotension, severe congestion, kidney dysfunction, malnutrition, frailty and multiorgan failure. Once these complications become profound or irreversible, transplantation may no longer provide acceptable benefit.

The 2025 Mayo Clinic consensus emphasizes that patients with cardiac amyloidosis and symptoms of advanced heart failure should receive specialist heart-failure evaluation (1).

Early referral provides time to:

• confirm the amyloid type;
• assess cardiac severity and hemodynamics;
• evaluate extracardiac organ involvement;
• optimize amyloidosis-specific treatment;
• improve nutritional and functional status where possible;
• clarify renal reversibility;
• consider isolated versus combined-organ transplantation; and
• engage the patient in informed shared decision-making.

Heart Transplantation Alone or Combined-Organ Transplantation?

Key Takeaways

• Cardiac amyloidosis is not an automatic contraindication to heart transplantation. Modern evidence supports transplantation in carefully selected patients with advanced AL or ATTR cardiomyopathy.
• Patient selection is critical. Clinicians must assess cardiac severity, extracardiac disease, frailty, nutrition, kidney function and overall expected benefit.
• Amyloid typing is essential. AL and ATTR require different disease-specific strategies before and after transplantation.
• Heart transplantation does not cure systemic amyloidosis. Control of the underlying amyloid-producing process remains necessary.
• Modern transplant outcomes are considerably better than historical outcomes. Several contemporary series report survival approaching that of non-amyloid transplant populations.
• Selected patients may require combined-organ transplantation. This may include heart–kidney or, much more selectively, heart–liver transplantation.
• Clinically significant recurrent amyloid in the transplanted heart appears uncommon in modern carefully selected cohorts. However, continued surveillance remains essential.
• Early referral matters. Advanced heart-failure assessment should occur before irreversible multiorgan deterioration eliminates transplant options.

Conclusion

Heart transplantation has become an important therapeutic option for a carefully selected subgroup of patients with advanced cardiac amyloidosis. Improvements in amyloid diagnosis, plasma-cell therapy, ATTR treatment, patient selection and transplant care have transformed outcomes compared with historical experience.

However, transplantation remains a highly individualized decision. The presence of advanced heart failure alone is not enough. Clinicians must determine whether extracardiac disease is limited or manageable, whether the underlying amyloid process can be controlled and whether transplantation is likely to provide meaningful long-term survival and quality of life.

The practical message is therefore clear: patients with cardiac amyloidosis who develop advanced heart failure should receive timely evaluation at a center with expertise in amyloidosis, advanced heart failure and transplantation.

References

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