Basics
Description
- Cardiac transplant recipients are a unique population with increased risk for cardiac ischemia, heart failure, as well as general risks as an immunocompromised host.
- 1,900-2,300 cardiac transplants per yr in US
- 1-yr survival 85-90%; 5-yr survival ~75%
- Typical immunosuppressive therapy to control rejection is a "triple-drug"Ł regimen often including steroids.
- Frequent biopsies are used initially to evaluate rejection; echocardiography often used in children.
- Complications occur most commonly in the 1st 6 wk after cardiac transplantation
- The proportion of elderly patients on the transplant list, and receiving transplants are increasing.
- Due to changes in immune system with age, elderly transplant recipients are at increased risk of life-threatening infections, and acute rejection.
- Pregnancy after cardiac transplant is becoming more common. Between 1988 and 2010, 63 women received either heart or heart-lung transplants. They have reported 108 pregnancies, all progressing to live births.
- Most common complications include hypertension, pre-eclampsia, and rejection.
- Physiologic changes that occur with pregnancy do not relate to increased rate of heart failure in transplant patients.
- Special attention should be paid to these patients regarding rejection and infection given their immunosuppression.
Etiology
- Rejection
- Hyperacute rejection
- Occurs within minutes of transplantation
- Rare, due to ABO or other graft/host major incompatibility
- Aggressive and immediately fatal to graft
- Acute rejection
- Lymphocyte infiltration and myocyte destruction
- Most common in 1st 6 wk
- May occur at any time
- 75% prevalence
- Chronic rejection
- Fibrosis and graft vascular disease
- Long-term complication
- Incompletely understood etiology
- No effective therapy
- Cardiac allograft vasculopathy
- Analogous to accelerated coronary artery disease in native hearts
- Limits long-term survival, leading cause of mortality after 1 yr
- Immune-mediated atherosclerosis
- Form of chronic rejection
- Infections
- 1st mo
- Bacterial infections are the most common cause of mortality during this high-risk time period
- Pneumonia (Pseudomonas, Legionella, other gram-negative organisms)
- Mediastinitis
- Wound infection
- UTI
- 1st yr
- Opportunistic and conventional infections
- Cytomegalovirus (CMV)
- Herpes simplex virus (HSV)
- Legionella
- Fungal infections
- Pneumocystis carinii
- Medication toxicity
- Cyclosporine, Neoral (2nd-generation cyclosporine), tacrolimus:
- Nephrotoxicity (30% incidence)
- Hepatotoxicity
- Neurotoxicity
- Hyperlipidemia, diabetogenic
- Azathioprine, mycophenolate mofetil:
- Bone marrow suppression
- Leukopenia
- Sirolimus:
- Hyperlipidemia
- Wound healing
- Steroids
- Osteoporosis
- Cushing disease
- Neoplasms
- Secondary to immunosuppression
- 10-100 times more common vs. general population
- Skin and lip cancer
- Lymphomas
- Kaposis sarcoma
- Solid organ neoplasms
- If the patient is not on steroids, bacteremia risk is similar to that in the general population.
- High incidence of pneumonia
- Patients on steroids may not show meningeal signs
Diagnosis
Signs and Symptoms
- Acute rejection
- Nonspecific symptoms predominate because the heart is usually denervated
- Fatigue
- Dyspnea
- Low-grade fever
- Nausea
- Vomiting
- May be difficult to differentiate between infection and acute rejection
- Heart failure
- Tachypnea
- Rales
- Hypoxia
- S3
- Murmur
- Edema
- Allograft vasculopathy
- As early as 3 months after transplantation (20-50% incidence by 5 yr)
- Denervated hearts do not present with typical angina.
- Insidious onset
- Acute onset
- Heart failure
- Sudden death
- Infarction
- Infection (Opportunistic and conventional)
- Fever
- Skin lesions (zoster)
- CMV
- Mild (flu-like illness)
- Fever
- Nausea
- Malaise
- Pneumonitis (13-50% mortality)
- Hepatitis
- Gastroenteritis
- Profound leukopenia
- Higher risk for post-transplant lymphoproliferative disease with Epstein-Barr virus seroconversion
- Like adults, at risk for allograft vasculopathy and its associated cardiac ischemia
Essential Workup
- Assess for signs of rejection, cardiac dysfunction, and infarction:
- ECG
- Cardiac enzymes
- Chest radiograph
- Echocardiography
- Possible rejection requires biopsy, consult transplant team.
Normal fever workup + chest radiograph and ECG; if on steroids, perform LP á
Diagnosis Tests & Interpretation
Lab
- Electrolytes:
- Cyclosporine effects:
- Increased blood urea nitrogen, creatinine
- Hyperkalemia
- Metabolic acidosis
- Hyponatremia
- CBC:
- Relative eosinophilia may indicate rejection over infection
- Blood and urine culture if febrile
- Lumbar puncture if seizures, altered mental status, or severe headache
- BNP (expect baseline elevation)
- CMV titers
- Urine antigen test
- Cyclosporine trough level
Imaging
- ECG
- Tachycardia
- 20% decrease in total voltage (nonsensitive)
- Note that normal rhythm for denervated heart is sinus 90-110 bpm
- Depending on transplant surgical technique, may see 2 P-waves (native and donor heart):
- Native P-waves do not correspond to quasi-random signal
- Chest radiograph
- Cardiomegaly
- Pulmonary edema
- Pleural effusions
- Compare with previous (healthy donor heart may appear large in small recipient)
- Echocardiography
- Decreased mitral deceleration time
- Initial diastolic dysfunction
- Biventricular enlargement
- Mitral/tricuspid regurgitation
Differential Diagnosis
- Rejection
- Infection
- Ischemia
- CMV
- Viral illness
- Malignancy
- Cyclosporine toxicity
Treatment
Pre-Hospital
Adenosine should not be given to patients who have had a heart transplant as the effects may be prolonged and unpredictable. á
Initial Stabilization/Therapy
- IV access
- Oxygen
- Monitor
- Intubation
- Defibrillation/pacing
- Vasopressors as required
- Arrhythmias
- Advanced cardiac life support
- Bradycardia does not respond to atropine; use isoproterenol
Ed Treatment/Procedures
- Hemodynamically significant rejection
- Methylprednisolone
- May also require OKT3 or other anti-T-cell antibody therapy
- Infarct/vasculopathy
- Aspirin
- Heparin
- Possible angioplasty
- Likely need retransplantation
- CMV
- HSV
- Gastroenteritis
- Search for CMV infection with culture, serology
- Fever without a source
- Consult infectious disease or transplantation team
- Headache
- Threshold for CT scan and lumbar puncture should be low (meningitis, abscess)
- Serious illness/trauma/operation
- Steroid burst
- Limit NSAID use because risk for renal insufficiency from cyclosporine and tacrolimus.
Medication
- Acyclovir: 5-10 mg/kg IV q8h calculate dose on IBW; genital herpes: 400 mg PO TID Ś 7-10 days; varicella: 20 mg/kg up to 800 mg PO QID for 5 days
- Ceftriaxone: 50 mg/kg IV q12-24h
- Cyclosporine, CellCept, tacrolimus, sirolimus, Neoral, azathioprine, mycophenolate mofetil: Per transplantation team
- Ganciclovir: Insert IV; 5 mg/kg BID for 2-3 wk (adjust for renal function)
- Isoproterenol: 1-4 ╬╝g/min, titrate to effect; max. 10 ╬╝g/min
- Methylprednisolone: 1 g IV; peds: 10-20 mg/kg IV
- OKT3, daclizumab or other antibody therapy: Per transplant team
In-Patient Considerations
Admission Criteria
- Hemodynamically significant rejection
- Vasculopathy/ischemia
- New dysrhythmia
- Poorly controlled hypertension
- Congestive heart failure
- Dyspnea
- Hypoxia
- Temperature >38 ░C in adult or child on steroids
- Suspected CMV (unexplained fever, gastroenteritis, or interstitial pneumonitis)
- Not tolerating oral medicines
- Syncope
Discharge Criteria
- Mild rejection
- Only in consultation with transplantation team
- Fever in nontoxic child:
- Do not give children stress-dose steroids
Additional Reading
- Abecassis áM, Bridges áND, Clancy áCJ, et al. Solid-organ transplantation in older adults: Current status and future research. Am J Transplant. 2012;12:2608-2622.
- Chinnock áR, Sherwin áT, Robie áS, et al. Emergency department presentation and management of pediatric heart transplant recipients. Pediatr Emerg Care. 1995;11(5):355-360.
- Cowan áSW, Davison áJM, Doria áC, et al. Pregnancy after cardiac transplantation. Cardiol Clin. 2012;30:441-452.
- Massad áMG. Current trends in heart transplantation. Cardiology. 2004;101:79-92.
- Mastrobattista áJM, Gomez-Lobo áV. Pregnancy after solid organ transplantation. Obstet Gynecol. 2008;112:919-932.
Codes
ICD9
996.83 Complications of transplanted heart á
ICD10
- T86.20 Unspecified complication of heart transplant
- T86.21 Heart transplant rejection
- T86.23 Heart transplant infection
- T86.22 Heart transplant failure
- T86.298 Other complications of heart transplant
SNOMED
- 233932001 Cardiac transplant disorder (disorder)
- 233933006 Cardiac transplant rejection (disorder)
- 429257001 Disorder of transplanted heart (disorder)