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Cardiac Transplantation Complications, Emergency Medicine

Basics

Description

- 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

- 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

- Electrolytes: - Cyclosporine effects: - Increased blood urea nitrogen, creatinine - Hyperkalemia - Metabolic acidosis - Hyponatremia

- 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

- Infarct/vasculopathy - Aspirin - Heparin - Possible angioplasty - Likely need retransplantation

- Serious illness/trauma/operation - Steroid burst - Limit NSAID use because risk for renal insufficiency from cyclosporine and tacrolimus.

  • 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

  • RejectionHyperacute rejectionOccurs within minutes of transplantationRare, due to ABO or other graft/host major incompatibilityAggressive and immediately fatal to graftAcute rejectionLymphocyte infiltration and myocyte destructionMost common in 1st 6 wkMay occur at any time75% prevalenceChronic rejectionFibrosis and graft vascular diseaseLong-term complicationIncompletely understood etiologyNo effective therapy
  • Cardiac allograft vasculopathyAnalogous to accelerated coronary artery disease in native heartsLimits long-term survival, leading cause of mortality after 1 yr
  • Immune-mediated atherosclerosisForm of chronic rejection
  • Infections1st moBacterial infections are the most common cause of mortality during this high-risk time periodPneumonia (Pseudomonas, Legionella, other gram-negative organisms)MediastinitisWound infectionUTI1st yrOpportunistic and conventional infectionsCytomegalovirus (CMV)Herpes simplex virus (HSV)LegionellaFungal infectionsPneumocystis carinii
  • Medication toxicityCyclosporine, Neoral (2nd-generation cyclosporine), tacrolimus:Nephrotoxicity (30% incidence)HepatotoxicityNeurotoxicityHyperlipidemia, diabetogenicAzathioprine, mycophenolate mofetil:Bone marrow suppressionLeukopeniaSirolimus:HyperlipidemiaWound healingSteroidsOsteoporosisCushing disease
  • NeoplasmsSecondary to immunosuppression10-100 times more common vs. general populationSkin and lip cancerLymphomasKaposis sarcomaSolid 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 rejectionNonspecific symptoms predominate because the heart is usually denervatedFatigueDyspneaLow-grade feverNauseaVomitingMay be difficult to differentiate between infection and acute rejection
  • Heart failureTachypneaRalesHypoxiaS3MurmurEdema
  • Allograft vasculopathyAs early as 3 months after transplantation (20-50% incidence by 5 yr)Denervated hearts do not present with typical angina.Insidious onsetAcute onsetHeart failureSudden deathInfarction
  • Infection (Opportunistic and conventional)FeverSkin lesions (zoster)CMVMild (flu-like illness)FeverNauseaMalaisePneumonitis (13-50% mortality)HepatitisGastroenteritisProfound 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:ECGCardiac enzymesChest radiographEchocardiography
  • 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, creatinineHyperkalemiaMetabolic acidosisHyponatremia
  • 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

  • ECGTachycardia20% decrease in total voltage (nonsensitive)Note that normal rhythm for denervated heart is sinus 90-110 bpmDepending on transplant surgical technique, may see 2 P-waves (native and donor heart):Native P-waves do not correspond to quasi-random signal
  • Chest radiographCardiomegalyPulmonary edemaPleural effusionsCompare with previous (healthy donor heart may appear large in small recipient)
  • EchocardiographyDecreased mitral deceleration timeInitial diastolic dysfunctionBiventricular enlargementMitral/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
  • ArrhythmiasAdvanced cardiac life supportBradycardia does not respond to atropine; use isoproterenol

Ed Treatment/Procedures

  • Hemodynamically significant rejectionMethylprednisoloneMay also require OKT3 or other anti-T-cell antibody therapy
  • Infarct/vasculopathyAspirinHeparinPossible angioplastyLikely need retransplantation
  • CMV
  • HSV
  • GastroenteritisSearch for CMV infection with culture, serology
  • Fever without a sourceConsult infectious disease or transplantation team
  • HeadacheThreshold for CT scan and lumbar puncture should be low (meningitis, abscess)
  • Serious illness/trauma/operationSteroid burstLimit 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)