Valve Transplant for Heart Valve Disease

Overseen By Sitaram Emani, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Disqualifiers: Morbid obesity, Diabetes, Immunocompromised, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1-2 weeks

4 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method for replacing heart valves using valves from organ donors, known as allogeneic valve transplantation. It targets individuals needing a new heart valve with limited replacement options, particularly those at risk of rejecting typical replacement valves. This treatment may suit individuals, including children, with significant growth potential who can travel to the trial site quickly. Participants must attend follow-ups and share their medical records for five years. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could expand future treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this valve transplant is safe for heart valve disease?

Research has shown that using heart valves from donors, known as allogeneic valve transplantation, has been the focus of several studies. In a nationwide study, researchers transplanted 25 donor heart valves into 20 patients, including various types such as aortic and pulmonary valves.

These studies aimed to assess safety and outcomes. They found that these transplants can be performed successfully, though risks exist as with any medical procedure. Common concerns include the body rejecting the new valve and potential infections. However, clinical settings carefully monitor and manage these risks.

While detailed information on side effects remains limited, the fact that multiple centers are studying these transplants suggests they hold promise for further research. This indicates potential safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for heart valve disease, which often involve mechanical or bioprosthetic valve replacements, allogeneic valve transplantation uses donor valves from another person. This approach offers a more natural fit and function, potentially reducing the risk of complications associated with synthetic materials. Researchers are excited about this treatment because it may improve the longevity of the valve replacement and enhance the patient's quality of life by mimicking the body's natural valve dynamics more closely. Additionally, this method could lead to better outcomes in terms of durability and integration with the patient’s existing heart tissue.

What evidence suggests that Allogeneic Valve Transplantation might be an effective treatment for heart valve disease?

Research has shown that using heart valves from donors, known as allogeneic valve transplantation, can effectively treat heart valve disease. Participants in this trial will undergo allogeneic valve transplantation. Studies have found that this method offers a long-lasting alternative to traditional artificial valves and does not require blood-thinning medications like Coumadin. Early results from a nationwide study showed excellent outcomes, with the transplanted valves functioning well over time. This suggests that allogeneic valve transplants could enhance the quality of life for patients needing valve replacement. ^{2 4 6 7 8}

Who Is on the Research Team?

Sitaram Emani, MD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

This trial is for patients with various heart valve diseases who require a new heart valve. Participants should need an aortic valve replacement and be suitable candidates for receiving valves from organ donors.

Inclusion Criteria

I need a heart valve replacement.

I have limited options for valve replacement.

Patients at risk of immunogenic bio-prosthetic valve failure

Exclusion Criteria

I have diabetes with complications affecting organs.

I do not have severe genetic, brain, or syndrome-related abnormalities.

I have HIV or chronic hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo allogeneic valve transplantation

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for valve regurgitation, valve annulus growth, ventricular function, and leaflet growth

1 year

Regular visits (in-person and virtual)

Long-term follow-up

Participants are monitored for survival and long-term outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Valve Transplantation

Trial Overview The study involves transplanting heart valves obtained from organ donors into patients with defective or diseased aortic valves, to see if this can effectively treat their condition.

How Is the Trial Designed?

Group I: Valve transplantation group Experimental Treatment 1 Intervention

This arm undergoes Allogeneic Valve transplantation

Allogeneic Valve Transplantation is already approved in European Union, United States for the following indications:

Approved in European Union as Allogeneic Valve Transplantation for:

• Congenital valve disease
• Infective endocarditis
• Small aortic roots
• Fertile women contemplating pregnancy

Approved in United States as Allogeneic Valve Transplantation for:

• Severe heart failure
• Severe valve dysfunction
• Prosthetic valve infection
• Invasion beyond the valve leaflets
• Recurrent systemic embolization
• Large mobile vegetations
• Persistent sepsis despite adequate antibiotic therapy

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

Partial heart transplantation is a promising new method for heart valve replacement that could provide durable, self-repairing valves without the need for anticoagulation therapy, making it particularly beneficial for young adults and those with specific health concerns.

This technique allows for the use of donor heart valves, potentially increasing the availability of suitable valves compared to traditional heart transplantation methods, although its clinical effectiveness in adults has yet to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial Heart Transplantation in Adult Cardiac Surgery. Sherard, C., Bisbee, C., Konsek, H., et al.[2023]

In a study of 10 allograft valves from heart transplant and valve replacement patients, histologic evaluation and DNA analysis revealed that in some heart transplant cases, receptor cells were found mixed with native donor cells, indicating a complex cellular environment.

The findings suggest that understanding the cellular origin of allograft valves could enhance preparation methods, although results for the valve replacement group are still inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The allograft valve in heart transplantation and valve replacement. Genetic assessment of the origin of the cells by means of deoxyribonucleic acid profiles. Melo, JQ., Monteiro, C., Neves, J., et al.[2006]

Heart valve allografts, or homografts, have been used for over 45 years in cardiac surgery and are particularly important for valve replacement in congenital heart disease, with around 700 grafts provided annually by tissue banks in the UK and Eire.

The article reviews the performance of homografts compared to prosthetic alternatives, discussing their clinical applications, degeneration, and future developments in homograft technology, highlighting their ongoing relevance in surgical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What tissue bankers should know about the use of allograft heart valves. Barron, DJ., Khan, NE., Jones, TJ., et al.[2016]

Fungal endocarditis, particularly from Candida albicans, is a rare but serious complication of allograft heart valve replacement, occurring in about 0.3% of cases, and often leads to unsuccessful treatment and death.

The investigation revealed that the antimicrobial processing used on the aortic valve allograft failed to completely eliminate C. albicans, highlighting a significant safety concern in the handling of donor tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candida albicans endocarditis associated with a contaminated aortic valve allograft--California, 1996. [2008]

In a study of 35 adult patients undergoing aortic valve replacement with cryopreserved human aortic valve allografts, those with active endocarditis experienced a higher perioperative mortality rate, with 2 deaths compared to none in the non-infected group, indicating a significant safety concern for infected patients (p<0.05).

Both groups showed no thromboembolic complications or recurrent infections during an average follow-up of 27 to 32 months, suggesting that the surgical techniques used (root-replacement and inclusion techniques) were effective in preventing these issues, regardless of infection status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allograft replacement of the aortic valve for active endocarditis. Ladowski, JS., Deschner, WP.[2016]

Out of 72,460 pediatric and young adult heart donations from 1987 to 2022, 43.3% (31,395) were discarded, indicating a significant potential source of valves for allogeneic valve transplantation.

The most common reasons for discarding these hearts included suboptimal graft function and poor organ function, suggesting that improving evaluation and allocation processes could enhance the availability of viable grafts for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in pediatric donor heart discard rates and the potential use of unallocated hearts for allogeneic valve transplantation. Nguyen, SN., Schiazza, A., Richmond, ME., et al.[2023]

In a study involving 32 rats, treatments with cyclosporine and anti-alpha4/beta2 integrin antibodies significantly reduced immune cell infiltration in allograft heart valves, helping to maintain their structural integrity after 7 days.

Long-term treatment with cyclosporine is necessary to prevent valve destruction, as a short 7-day course was insufficient to preserve the valves' integrity after 28 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of allograft heart valve failure in a rat model. Légaré, JF., Ross, DB., Issekutz, TB., et al.[2013]

Aortic valve replacement with human allograft valves shows a host-graft interaction that varies based on the sterilizing and storage methods used before implantation.

A new canine experimental model has been developed to study the patterns of tissue ingrowth in allografts treated with different methods, providing insights into optimizing graft performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monocusp aortic valve replacement in dogs: an experimental model. Goldstein, J., Robinson, MC., McDonald, GR., et al.[2019]

In a study involving 24 Lewis rats and 12 T cell-deficient nude rats, allograft heart valves were found to fail due to T cell-mediated immune damage, leading to structural destruction over time.

Syngeneic grafts remained structurally intact with minimal immune response, while allogeneic grafts showed significant immune infiltration and damage, indicating that T cells play a critical role in the rejection of transplanted heart valves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T lymphocytes mediate leaflet destruction and allograft aortic valve failure in rats. Legare, JF., Lee, TD., Creaser, K., et al.[2019]

Citations

1. jtcvs.org jtcvs.org/article/S0022-5223(23)00861-9/fulltext

Living allogenic heart valve transplantation: Relative ... LAVT also could improve outcomes in adult cardiac surgery by providing a structurally durable coumadin-free alternative to bioprotheses and ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37743011/

Living allogenic heart valve transplantation Living allogenic heart valve transplantation: Relative advantages and unanswered questions. J Thorac Cardiovasc Surg. 2024 May;167(5):1543-1546.

3. sciencedirect.com sciencedirect.com/science/article/pii/S295013342500179X

A STRUCTURED INSTITUTIONAL FRAMEWORK FOR ... Living allogenic valve transplantation (LAVT) refers to transplantation of viable human heart valves in an orthotopic or heterotopic fashion ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666634024002630

Storage, preservation, and rehabilitation of living heart ... Living allogeneic valve transplantation (LAVT, also known as partial heart transplantation) has recently been introduced as a means of delivering replacement ...

5. aats.org aats.org/resources/abstract.pdf?abstract=2696747

A Nation-Wide Multicenter Study Conclusions: This nation-wide multicentric study of all HVT recipients shows that early outcomes of semilunar HVTs are excellent with preserved function and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39842543/

The case for a multicenter prospective clinical registry Evaluating safety and outcomes of living allogenic heart valve transplantation: The case for a multicenter prospective clinical registry.

7. researchgate.net researchgate.net/publication/388203514_Evaluating_Safety_and_Outcomes_of_Living_Allogenic_Heart_Valve_Transplantation_The_Case_for_a_Multicenter_Prospective_Clinical_Registry

The Case for a Multicenter Prospective Clinical Registry Evaluating Safety and Outcomes of Living Allogenic Heart Valve Transplantation: The Case for a Multicenter Prospective Clinical Registry.

8. jtcvsopen.org jtcvsopen.org/article/S2666-2736(23)00127-4/fulltext

Trends in pediatric donor heart discard rates and the ... With ∼900 pediatric/young adult donor hearts discarded annually, unutilized grafts represent a potential source of valves for allogeneic valve transplant.