Heart Transplantation - Complete University Exam Review

1. Background and Epidemiology

2. Indications and Contraindications

Indications (ISHLT Guidelines)

• ACC/AHA Stage D heart failure refractory to guideline-directed medical therapy (GDMT)
• Mechanical circulatory support (MCS) dependence
• Inotrope dependence
• Cardiopulmonary exercise testing (CPET): peak VO2 ≤14 mL/kg/min (not on beta-blocker) or ≤12 mL/kg/min (on beta-blocker)

Absolute Contraindications

Relative Contraindications

• Age >70 years (U-shaped mortality relationship - increased risk <18 and >65 years)
• PVR 4-6 Wood units (should be reduced medically first)
• Diabetes with end-organ damage or HbA1c >7.5%
• Symptomatic peripheral/cerebrovascular disease not amenable to revascularization
• Active substance abuse; severe obesity; psychosocial instability

3. Pre-Transplant Evaluation of the Candidate

• Labs: CBC, BMP, LFTs, urinalysis, coagulation, thyroid, HIV, hepatitis B/C, CMV IgG/IgM, RPR/VDRL, panel-reactive antibodies (PRA), ABO/Rh, lipids, HbA1c
• Imaging: Chest X-ray, PFTs, echocardiography
• Hemodynamics: Right and left heart catheterization (critical for PVR assessment)
• CPET: Peak VO2 measurement
• Malignancy screening: Age-appropriate
• Psychosocial evaluation: substance use history, mental health, social support

4. Donor Selection and Organ Allocation

Donor Criteria

• ABO compatibility is mandatory; HLA matching is not routinely required but anti-HLA antibody screening (PRA/DSA) is performed
• Size and sex matching: donor-to-recipient weight ratio typically 0.75-1.5; female donors to male recipients carry higher risk
• Donation after brain death (DBD) is standard; donation after circulatory death (DCD) is increasingly used
• Ischemic time should ideally be <4-6 hours (prolonged cold ischemia increases primary graft dysfunction risk)

Allocation System (UNOS/OPTN - revised 2018)

5. Cardiac Allograft Preservation

• Donor heart is arrested with cold cardioplegia solution (most commonly University of Wisconsin or HTK Custodiol)
• Standard cold static storage at 4°C
• Normothermic machine perfusion (NMP) - newer technology (OCS Heart device) allows the heart to beat in a perfused, oxygenated state during transport, extending preservation time and enabling use of DCD hearts
• Ischemic time remains a critical determinant of outcomes

6. Surgical Technique

Recipient Operation

• Performed via median sternotomy on cardiopulmonary bypass (CPB)
• Recipient heart is excised, leaving cuffs of the great vessels and atria

Orthotopic Heart Transplantation - Two Techniques

• Original technique (1960s)
• Anastomoses: left atrium (posterior cuff), right atrium, pulmonary artery, aorta
• Leaves large recipient atrial cuff - associated with sinus node dysfunction

• Separate anastomoses of superior vena cava (SVC) and inferior vena cava (IVC)
• Better preservation of sinus node function; lower rates of tricuspid regurgitation
• Anastomosis order: Left atrium → IVC → pulmonary artery → aorta → SVC

Special Considerations

• Prior LVAD recipients: cannula sites must be managed carefully
• Congenital heart disease: Fontan patients, situs inversus, and transposition of the great arteries require modified approaches with augmentation of pulmonary arteries and great vessels

7. Immunosuppression

Induction Immunosuppression

Steroid Weaning

8. Cardiac Allograft Rejection

Types of Rejection

• Occurs within minutes to hours of reperfusion
• Caused by preformed donor-specific antibodies (DSAs) - ABO incompatibility or preformed anti-HLA antibodies
• Leads to rapid, irreversible graft failure
• Prevented by ABO matching and crossmatch testing

• T-lymphocyte mediated destruction of allograft tissue
• Most common in first 6-12 months
• Histology: lymphocytic myocardial infiltrates, myocyte damage
• ISHLT grading:
  • Grade 0R: No rejection
  • Grade 1R (mild): Interstitial/perivascular infiltrate with ≤1 focus of myocyte damage
  • Grade 2R (moderate): ≥2 foci of infiltrate with myocyte damage
  • Grade 3R (severe): Diffuse infiltrate with multifocal myocyte damage ± edema, hemorrhage, vasculitis
• Treatment: High-dose IV corticosteroid pulses; hemodynamic compromise → add ATG

• Driven by donor-specific antibodies (DSAs) fixing complement on allograft endothelium
• Histology: endothelial swelling, interstitial edema, capillary injury; immunostaining positive for C3d and C4d
• pAMR grading (0, 1H+, 1I+, 2, 3)
• Worse prognosis than ACR; major risk factor for cardiac allograft vasculopathy (CAV)
• Treatment: Plasmapheresis, IVIG, rituximab (anti-CD20); refractory cases: bortezomib, eculizumab

Monitoring for Rejection

• Endomyocardial biopsy (EMB): Gold standard - performed via transjugular or transfemoral approach using biopsy forceps catheter; H&E staining + immunohistochemistry for C3d/C4d
• Routine protocol biopsies especially in first 6 months
• Gene expression profiling (GEP) - non-invasive alternative to biopsy for low-risk patients
• Echocardiography: decreased function suggests clinically significant rejection

9. Complications

Early Complications

Late Complications

10. Survival and Outcomes

• Median survival: approximately 12-13 years (ISHLT Registry)
• 1-year survival: ~85%
• 5-year survival: ~70-75%
• 10-year survival: ~55%
• Quality of life: Significantly improved; most recipients return to NYHA Class I-II
• Leading causes of death:
  • First 30 days: Primary graft dysfunction, technical failures
  • 1 month - 1 year: Infections, acute rejection
  • Beyond 1 year: CAV, malignancy, renal failure

11. Bridging Strategies (Pre-Transplant)

• Inotropic infusions (dobutamine, milrinone)
• Intra-aortic balloon pump (IABP)
• Temporary MCS: Impella, ECMO (bridge to transplant or decision)
• Durable LVAD (left ventricular assist device): Bridge to transplant; ~50% of transplant recipients are on LVAD at time of transplant; transplant outcomes equivalent to non-LVAD patients

Key Points for Exam

1. Indication: ACC/AHA Stage D HF; peak VO2 ≤14 (no BB) or ≤12 (on BB) mL/kg/min
2. Absolute contraindication: PVR >6 Wood units (consider heart-lung transplant)
3. Preferred surgical technique: Bicaval orthotopic transplantation
4. Standard immunosuppression: Tacrolimus + MMF + prednisone
5. Leading early cause of death: Primary graft dysfunction
6. Rejection monitoring: Endomyocardial biopsy (ISHLT grading)
7. ACR treatment: IV methylprednisolone pulses ± ATG
8. AMR treatment: Plasmapheresis + IVIG ± rituximab
9. Most important late complication: CAV (~30% at 5 years, ~50% at 10 years)
10. Median survival: ~12-13 years; 1-year survival ~85%

1. Background - epidemiology, common etiologies (ischemic CM most common)
2. Indications & Contraindications - ISHLT criteria, peak VO2 thresholds, absolute vs. relative contraindications (PVR >6 Wood units = absolute)
3. Candidate evaluation - full multidisciplinary workup including hemodynamics and CPET
4. Donor selection & UNOS allocation - ABO compatibility, size matching, the 2018 6-tier status system, DCD vs. DBD
5. Allograft preservation - cold static storage, normothermic machine perfusion (OCS Heart)
6. Surgical technique - biatrial (classic) vs. bicaval (preferred) orthotopic transplantation; anastomosis sequence
7. Immunosuppression - triple therapy (tacrolimus + MMF + prednisone), mechanism and side effects of each drug class, induction agents
8. Rejection - all 3 types (hyperacute, ACR, AMR), ISHLT grading, diagnosis by endomyocardial biopsy, treatment protocols
9. Complications - early (primary graft dysfunction, RV failure) and late (CAV, malignancy, CKD, PTLD)
10. Outcomes - ~85% 1-year survival, ~12-13 year median survival; leading causes of death by time period
11. Bridging strategies - LVAD, IABP, ECMO

Orthotopic Heart Transplantation: Two Techniques, Simply Explained

Technique 1: Biatrial (Classic / Lower-Shumway)

Developed by Norman Shumway at Stanford in the 1960s. Used for the first human heart transplant.

The Big Idea

Joins Made (4 total)

1. Left atrium - donor LA sewn to recipient LA cuff (which includes the pulmonary vein openings)
2. Right atrium - donor RA sewn to recipient RA cuff (which includes the SVC and IVC openings)
3. Pulmonary artery - end to end
4. Aorta - end to end

Think of it as:

The Problem

• The right atrial cuff contains the recipient's sinus node (the heart's natural pacemaker)
• Now there are two sinus nodes - one from the donor, one from the recipient
• This can cause sinus node dysfunction, irregular rhythms, and the need for a pacemaker
• The large atrial remnant can also cause tricuspid valve regurgitation (leaky valve)

Technique 2: Bicaval (Modern / Preferred Today)

Developed in the 1990s. Now the standard technique at most centers.

The Big Idea

Joins Made (5 total)

1. Left atrium - same as biatrial (recipient LA cuff sewn to donor LA)
2. Inferior vena cava (IVC) - sewn directly, end to end
3. Superior vena cava (SVC) - sewn directly, end to end
4. Pulmonary artery - end to end
5. Aorta - end to end

Order of anastomoses in the OR:

Why it's better

• The entire donor right atrium is preserved intact, including the donor's own sinus node
• Only one sinus node = much better heart rhythm
• Less tricuspid regurgitation
• More physiological blood flow through the right side

Side-by-Side Comparison

Visual Summary (The Surgical Image Above)

• (A) Left atrial anastomosis - the back wall of the left atrium is sewn first
• (B) IVC and SVC joined individually - the two big veins are connected one at a time
• (C) Pulmonary artery and aorta joined - the final two tubes are connected, then the clamp is released and the heart is reperfused

One-Line Memory Aid

Biatrial = 2 atrial "sleeves" kept → 2 pacemakers → problems Bicaval = each vein sewn separately → 1 pacemaker → better rhythm → preferred