MED-NERD

Heart failure and Cardiac transplantation

Updated: August 26, 2022

Outline:

• Overview

• Prevalence

• Cardiac transplantation

• Key facts

• Indications for cardiac transplantation

• Complications of cardiac transplantation

• Contraindications of cardiac transplantation

• Outcomes and survival rate of cardiac transplantation

• Conclusion

• References

Overview : 

Heart failure (HF) is a clinical syndrome  which is defined as any structural or functional defect of ventricular filling or ejection of blood. Manifestations of HF include fatigue, dyspnea, fluid retention, pulmonary congestion, peripheral oedema and exercise intolerance.

Prevalence: 

• About 64.3 million people have HF worldwide. 
• In the United States, 6.2 million adults diagnosed having HF.
• In 2018, HF caused 379,800 deaths.

Cardiac transplantation: 

Advanced stages of HF show poor response to medical treatment. Cardiac transplantation is the best choice for these cases. After cardiac transplantation, one-year survival rate is about 90% and has 13 years of conditional half-life. One of the Restrictions of cardiac transplantation is the limited number of donors.

Key facts : 

• On 3 December 1967: Christiaan Barnard  performed the first human-to-human cardiac transplantation and due to infective complications, the patient died 18 days later.
• In 1980s: The discovery of ciclosporin improved the survival rate in cardiac transplantation which peaked in early 1990s.
• In recent years: The number of cardiac transplantation has increased up to > 5000 yearly worldwide.
• In 2019:  According to the American Heart Association, Almost 3,552 cardiac transplantations were performed  in the United States.
• In Jan 2022: The University of Maryland Medical Centre and the University of Maryland School of Medicine announced  the first successful cardiac transplantation of a genetically modified pig’s heart into a human. Although the patient died two months later, this operation is considered  a breakthrough in cardiac transplants.

Indications for cardiac transplantation : 

According to The American College of Cardiology (ACC) and the American Heart Association (AHA) guidelines, indications for cardiac transplantation include :

• Refractory cardiogenic shock requiring intra-aortic balloon pump counter pulsation or left ventricular assist device (LVAD).

• Cardiogenic shock requiring continuous intravenous inotropic therapy (i.e., dobutamine, milrinone, etc.).

• Peak VO2 (VO2max) less than 10 mL/kg per min.

• New York Heart Association (NYHA) functional classifications of heart failure class of III or IV despite maximized medical and resynchronization therapy.

• Recurrent life-threatening left ventricular arrhythmias despite  antiarrhythmic therapy, an implantable cardiac defibrillator, or catheter-based ablation.

• End-stage congenital HF with no evidence of pulmonary hypertension.

• Refractory angina without potential medical or surgical therapeutic options.

Complications of cardiac transplantation : 

-Complications of cardiac transplantation include the following:

1-Acute rejection : 

-It is a major cause of death after transplantation .

-It is T-cell mediated inflammation characterized by lymphocyte infiltration, oedema and myocyte necrosis .

-Usually occurs in the first 6 months and about 24% in the first 12 months.

-Recently , it has a low incidence as a result of modern drug therapies.

-Endomyocardial biopsy (EMB) is considered the gold standard for following up heart functions and detection of rejection.

* It is an invasive procedure to reach the right ventricle by inserting a bioptome into right femoral vein or right jugular vein using fluoroscopy or echocardiography and samples are taken from the interventricular septum.

*Complications of this procedure include: right bundle branch block, tricuspid regurgitation, and right ventricular perforation .

 

2-Coronary artery vasculopathy (CAV):

-It involves immune and non-immune mechanisms.

-It occurs from 30% to 40% after transplantation within 5 years .

-For screening of CAV, the following techniques are used:

1. Angiography: It  is considered the standard of care for surveillance of the coronary arteries for CAV after heart transplantation. The prevalence of angiographic CAV is 7.8% at 1 year and 47% at 10 years after transplantation.
2. Dobutamine stress echocardiography: It has a sensitivity of between 70% and 80% for detecting significant CAV .
3. Exercise stress echocardiography: It has a low sensitivity for detecting CAV due to denervation of transplanted heart and its inability to reach the heart rates required for exercise .
4. Intravascular ultrasound: It is considered the new gold standard technique for detecting CAV by visualising the vessel wall. It is more sensitive than angiography in detecting early CAV.

3-Infection: 

-Caused by immunosuppressive therapy that is used to reduce the risk of rejection.

-Bacteria and viruses cause about 80% of post-operative infection.

-Bacterial infection is nosocomial and usually caused by infected intravascular catheter or gram-negative pneumonias.

4-Malignency :

-Represents about 10% to 23% of all deaths following cardiac transplantation.

-Cutaneous malignancy is the most common type accounting for 17% of patients, with a predominance of squamous cell carcinoma. 

5-Post-transplantation lymphoproliferative disorder (PTLD):

-It is a fatal complication accounting for 1.7% to 6% .

-Maximumly occurs within 3 to 4 months following cardiac transplantation.

-Usually associated with Epstein-Barr virus.

6-Renal dysfunction: 

-It is calcineurin inhibitor-induced nephrotoxicity.

-Cyclosporine causes the greatest decline in the Glomerular filtration rate (GFR) in the first 3 to 6 months.

-The use of calcineurin inhibitors for immunosuppression leads to developing stage four-kidney disease (with a GFR <30 mL/min) in about 10% of recipients which requires kidney transplantation or renal replacement therapy.

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Contraindications of cardiac transplantation : 

• Advanced irreversible renal failure with Cr >2 or creatinine clearance <30-50 mL/min.

• Advanced irreversible liver disease.

• Advanced irreversible pulmonary parenchymal disease .

• Advanced irreversible pulmonary artery hypertension .

• History of solid organ or hematologic malignancy within the last 5 years due to probability of recurrence.

• Severe peripheral vascular disease.

• Severe cerebrovascular disease.

• Severe osteoporosis.

• Severe obesity (BMI >35 kg/m2) or cachexia.

• Acute pulmonary embolism.

• Active infection.

• Advanced age (>70 years old).

• Psychological instability .

• Active or recent substance abuse  (within 6 months) (including : alcohol, cocaine, opioids, tobacco products, etc.).

• Diabetes mellitus with end organ damage.

• Lack of social support or sufficient resources to permit ongoing access to immunosuppressive medication and frequent medical follow-up.

Outcomes and Survival rate : 

- In case of paediatric heart transplant recipients, the outcomes are excellent. About 80% for 5-year and 65% for 10-year post-transplant survival rate. 

-For adults, the 1-year survival rate is about 90%, the 5-year survival rate is about 70%, but it is nearly 20% survival rate for 20 years or longer.

-Patients are usually able to return to work after transplantation with good quality of life .

Conclusion:

Heart failure is a major challenge that threatens lives of many patients. Cardiac transplantation is considered a good choice for treatment of End-stage heart failure although it has complications and contraindications. The limited number of donors  encouraged researchers to find other solutions such as genetically modified pig's heart. The research is still ongoing.

References :

(1)  American Heart Association. 2022. Groundbreaking pig heart transplant in a human may help patients awaiting donor hearts. [online] Available at: <https://newsroom.heart.org/news/groundbreaking-pig-heart-transplant-in-a-human-may-help-patients-awaiting-donor-hearts> 

(2) Nytimes.com. 2022. Patient in Groundbreaking Heart Transplant Dies. [online] Available at: <https://www.nytimes.com/2022/03/09/health/heart-transplant-pig-bennett.html>.

(3) Kittleson, M., 2022. Recent advances in heart transplantation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039932/

(4) Ubeda Tikkanen, A., Berry, E., LeCount, E., Engstler, K., Sager, M. and Esteso, P., 2022. Rehabilitation in Pediatric Heart Failure and Heart Transplant.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170027/

(5)Kępińska K, Adamczak DM, Kałużna-Oleksy M. Advanced 

heart failure: A review. Adv Clin Exp Med. 2019;28(8)

https://www.sciencedirect.com/science/article/pii/S1936878X18306405?via%3Dihub

(6) Alraies, M. and Eckman, P., 2022. Adult heart transplant: indications and outcomes. [online] PubMed Central (PMC). Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133547/>.

(7) Bozkurt, B., Coats, A., Tsutsui, H., Abdelhamid, M., Adamopoulos, S., Albert, N., Anker, S., Atherton, J., Böhm, M., Butler, J., Drazner, M., Felker, G., Filippatos, G., Fonarow, G., Fiuzat, M., Gomez-Mesa, J., Heidenreich, P., Imamura, T., Januzzi, J., Jankowska, E., Khazanie, P., Kinugawa, K., Lam, C., Matsue, Y., Metra, M., Ohtani, T., Francesco Piepoli, M., Ponikowski, P., Rosano, G., Sakata, Y., SeferoviĆ, P., Starling, R., Teerlink, J., Vardeny, O., Yamamoto, K., Yancy, C., Zhang, J. and Zieroth, S., 2022. Universal Definition and Classification of Heart Failure.

https://www.onlinejcf.com/article/S1071-9164(21)00050-6/fulltext

(8) https://www.cdc.gov/heartdisease/heart_failure.htm

(9) https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.1858

(10)Bhagra, S., Pettit, S. and Parameshwar, J., 2022. Cardiac transplantation: indications, eligibility and current outcomes.

https://heart.bmj.com/content/105/3/252.abstract