301.1 🎓 醫孞生版

301.1.0.1 📌 䞀頁重點

301.1.0.1.1 Indications + Contraindications
301.1.0.1.1.1 Indications for Heart Transplantation
  • Stage D HF (refractory):
    • NYHA III-IV despite optimal medical therapy
    • Recurrent hospitalizations
    • EF < 25% in selected
    • Life-threatening arrhythmias
  • Persistent cardiogenic shock despite MCS bridge
  • Congenital heart disease with severe biventricular failure
  • Refractory angina not amenable to revascularization
  • HFpEF with severe symptoms (less common)
  • Pulmonary hypertension + CHD (heart-lung transplant)
301.1.0.1.1.2 Contraindications
  • Active malignancy (within 5 yr, depending on type/stage)
  • Active infection (untreated)
  • Severe fixed pulmonary HTN (PVR > 4-5 WU non-responsive to vasodilator)
  • Severe end-organ damage (CKD ESRD without renal transplant plan, severe liver, etc.)
  • Active substance abuse (within 6 months)
  • Psychosocial issues (non-adherence, lack of support)
  • Morbid obesity (BMI > 35-40 typically)
  • Severe peripheral / cerebrovascular disease
  • Advanced age (relative; case-by-case in 70+)
  • Diabetes with severe end-organ damage
  • HIV with poor viral control (advancing in HIV-naive patients)
301.1.0.1.1.3 Listing Status (UNOS)
  • Listed urgency:
    • Status 1A → 1B → 2 → 7
    • 2018 changes: increased granularity for high-acuity
    • Status 1 = mechanical support + temporary support + high inotrope
301.1.0.1.2 Mechanical Circulatory Support (MCS)
301.1.0.1.2.1 Temporary MCS

Intra-Aortic Balloon Pump (IABP) - For acute decompensation - Diastolic counterpulsation → coronary perfusion ↑ - ↓ Afterload - Less aggressive support - IABP-SHOCK II trial — no mortality benefit in routine STEMI cardiogenic shock - Bridge in select cases (mechanical complications, refractory angina)

Impella (Axial Flow Pump) - Microaxial pump in LV - Models: 2.5 (2.5 L/min), CP (3.5 L/min), 5.0 (5.0 L/min), 5.5 (5.5 L/min) - For acute MI cardiogenic shock, high-risk PCI, refractory shock - DanGER-SHOCK 2024: benefits in select shock - Hemolysis, vascular complications, limb ischemia

Tandem Heart (Centrifugal LVAD) - LA → femoral vein → centrifugal pump → femoral artery - Higher flow than Impella 2.5/CP

VA-ECMO (extracorporeal) - Heart + lung support - Configurations: peripheral (femoral) or central - Indications: cardiac arrest (E-CPR), severe cardiogenic shock, refractory - Complications: limb ischemia, stroke, bleeding, hemolysis - ECPELLA: VA-ECMO + Impella (LV decompression)

Right Ventricular Support - ProTek Duo (RV → PA) - Used for RV failure post-LVAD or other

301.1.0.1.2.2 Durable MCS (LVAD)

HeartMate 3 (Modern LVAD) - Magnetically levitated centrifugal flow pump - No mechanical bearings → less thrombosis, less hemolysis - MOMENTUM 3 (2017, 2024 long-term): changed LVAD outcomes - 5-year survival ~ 75% (similar to transplant for select) - Continuous flow (no pulse) - Driveline through abdominal wall - Battery + controller

Indications for LVAD - Bridge to transplant (BTT): listed candidates waiting - Bridge to candidacy (BTC): not yet listed; may improve to listing - Destination therapy (DT): not transplant candidate; lifelong device - Bridge to recovery (BTR): rare, possible in select (myocarditis, peripartum)

LVAD Complications - Bleeding (GI, intracranial, surgical) — top complication - Stroke — ~ 10-15% over 5 years (less with HM3) - Pump thrombosis — less with HM3 - Driveline infection — common, lifelong risk - Right ventricular failure — post-implant - Aortic insufficiency — develops over time - Arrhythmia — VT/VF (mostly tolerated due to LVAD bridging)

Quality of Life - ↑ Functional capacity - ↓ Hospitalizations - Battery management, driveline care lifelong - Restrictions: no full submersion, careful contact sports

301.1.0.1.2.3 Total Artificial Heart (TAH, SynCardia)
  • Replaces both ventricles
  • Used as BTT for biventricular failure
  • Less common with HM3 LVAD success
301.1.0.1.2.4 Right Ventricular Assist Device (RVAD)
  • Centrimag, ProTek Duo
  • Often temporary
  • BiVAD configurations possible
301.1.0.1.3 The Cardiac Transplant Process
301.1.0.1.3.1 Pre-Transplant Evaluation
  • Comprehensive medical history + physical
  • CV: echo, RHC, stress test, exercise capacity
  • Renal, hepatic, pulmonary, neuro
  • Cancer screening
  • Infectious workup (HIV, HepB/C, CMV, EBV, VZV, etc.)
  • Psychosocial + adherence
  • Pulmonary HTN reversibility (vasodilator response)
  • HLA testing
  • Frailty assessment
301.1.0.1.3.2 Listing
  • UNOS listing
  • Status determined by clinical state
  • Wait time variable (weeks to years)
  • Geographic variability
301.1.0.1.3.3 Donor Selection
  • Brain-dead donor
  • Donor heart matched: blood type, size, age, sex (relative)
  • Ischemic time < 4-6 hours optimal
  • Modern: ex-vivo perfusion (OCS Heart) for longer preservation
301.1.0.1.3.4 Donor Heart Procurement + Implantation
  • Bicaval anastomosis modern preferred (vs biatrial)
  • Cardiopulmonary bypass
  • Right atrium anastomosis (or bicaval)
  • Aortic + pulmonary artery anastomosis
  • Re-perfusion + weaning bypass
301.1.0.1.3.5 Post-Op Management
  • ICU monitoring
  • Hemodynamic support
  • Immunosuppression initiation
  • Antibiotic prophylaxis
  • Heart rhythm monitoring (often denervated)
301.1.0.1.4 Post-Transplant Care
301.1.0.1.4.1 Immunosuppression

Induction: - ATG (anti-thymocyte globulin) - IL-2 receptor antagonist (basiliximab, daclizumab) - High-dose steroids

Maintenance: - Calcineurin inhibitor (CNI): - Tacrolimus (preferred, target trough 10-15 ng/mL early, 5-10 chronic) - Cyclosporine - Antiproliferative: - Mycophenolate mofetil (MMF) preferred - Azathioprine - Corticosteroids: prednisone (tapered over months) - mTOR inhibitor (sirolimus, everolimus): for CAV, malignancy reduction; not first-line

301.1.0.1.4.2 Rejection Surveillance
  • Endomyocardial biopsy (EMB) routinely
  • Weekly initially, then less frequent
  • Lake Louise CMR for non-invasive monitoring
  • Non-invasive markers: cell-free DNA, gene expression profiling (AlloMap)
  • AlloMap (gene expression profiling): peripheral blood; for low-risk patients
  • Donor-derived cell-free DNA (cfDNA): emerging marker
  • Treatment: increase immunosuppression, plasmapheresis for antibody-mediated rejection
301.1.0.1.4.3 Acute Rejection Types
  • Acute cellular rejection (ACR): T-cell mediated, mild-moderate-severe (ISHLT grade 1R-3R)
  • Antibody-mediated rejection (AMR): anti-HLA antibodies, plasmapheresis + IVIG + rituximab
  • Hyperacute rejection: pre-formed antibodies (rare with crossmatch screening)
301.1.0.1.4.4 Cardiac Allograft Vasculopathy (CAV)
  • Top cause of late mortality post-transplant
  • Diffuse intimal hyperplasia + atherosclerosis
  • Often silent (denervated heart, no angina)
  • Diagnosis: annual coronary angiography + IVUS
  • Risk factors: rejection, CMV, dyslipidemia, IS effects, donor characteristics
  • Treatment: statins (aggressive), ASA, optimize CV risk factors
  • mTOR inhibitor (sirolimus, everolimus) for slowing CAV
  • Severe CAV: re-transplantation
301.1.0.1.4.5 Complications + Long-Term Issues

Cardiovascular: - CAV - HTN (from CNI, steroids) - Hyperlipidemia - Diabetes mellitus - Arrhythmias

Infectious: - CMV, EBV, HSV, VZV, PJP (Pneumocystis), aspergillus, candida, BK virus - Prophylaxis: valganciclovir (CMV), TMP-SMX (PJP), antifungals as needed

Malignancy: - Skin cancer (most common): UV protection, surveillance - Lymphoproliferative disease (PTLD): EBV-driven - Solid organ cancers: lung, GI, prostate increased

Renal Dysfunction: - CNI nephrotoxicity - Hypertension - DM - Combined: 25-30% develop ESRD over years

Bone Loss: - Steroids - Osteoporosis surveillance - Bisphosphonates

Mental Health: - Depression, anxiety - Counseling, SSRIs as needed

301.1.0.1.5 Outcomes
301.1.0.1.5.1 Survival
  • 1-year: ~ 90%
  • 5-year: ~ 75%
  • 10-year: ~ 50-60%
  • 20-year: ~ 25-30%
301.1.0.1.5.2 Quality of Life
  • Generally excellent
  • Return to functional activities
  • Some restrictions (exercise initially, immunocompromise considerations)
301.1.0.1.6 Heart-Lung Transplant
301.1.0.1.6.1 Indications
  • Eisenmenger syndrome
  • Severe PAH with biventricular failure
  • Combined cardiac + pulmonary disease
301.1.0.1.6.2 Outcomes
  • Lower survival than heart alone or lung alone
  • 1-year ~ 70%, 5-year ~ 50%
301.1.0.1.7 Future Directions
301.1.0.1.7.1 Xenotransplantation
  • Genetically modified pig hearts
  • First human implant 2022 (David Bennett, University of Maryland) — 2 months survival
  • Second 2023, similar challenges
  • Lawrence Faucette 2023 → 40 days
  • Hyperacute rejection challenge
  • Multiple gene-edited (10+ genes) pigs in development
301.1.0.1.7.2 iPS-Derived Cardiomyocytes
  • Induced pluripotent stem cells → cardiomyocyte
  • For myocardial regeneration
  • BIOSTAR-CMS, others
  • Early trials
301.1.0.1.7.3 CRISPR / Gene Therapy
  • For genetic cardiomyopathies (HCM, DCM)
  • HCM: gene editing to correct sarcomere mutations
  • Long way to clinical
301.1.0.1.7.4 Mechanical Circulatory Support Evolution
  • Smaller, more durable LVADs
  • Total artificial heart improvements
  • Battery improvements
  • Wireless power transfer
301.1.0.1.7.5 Personalized Immunosuppression
  • Tailored regimens based on rejection risk
  • Cell-free DNA monitoring
  • Biomarker-guided therapy

301.1.0.2 🩺 床邊速查

  • Transplant indications: refractory HF NYHA III-IV + EF < 25% + optimal medical therapy
  • Contraindications: active malignancy, severe fixed PH, substance abuse, severe comorbidities
  • MCS hierarchy: IABP → Impella → Tandem Heart → VA-ECMO → LVAD (durable)
  • HeartMate 3 (MOMENTUM 3): modern LVAD, 5-yr survival ~ 75%, less thrombosis
  • Immunosuppression: induction (ATG / basiliximab) + maintenance (tacrolimus + MMF + steroid)
  • CAV: top cause of late mortality; annual angiography; mTOR inhibitor for slowing
  • EMB: gold standard for rejection; AlloMap + cfDNA non-invasive
  • Future: xenotransplantation, iPS cardiomyocytes