301.3 🏥 內科專科考前版

301.3.1 Mechanistic Deep Dive

301.3.1.1 Denervated Heart Physiology

  • Loss of vagal + sympathetic input acutely
  • ↑ Resting HR (90-100)
  • Loss of Frank-Starling reserve initially
  • Recovery over months-years
  • Direct catecholamine response intact
  • Less sensitive to baroreflex

301.3.1.2 Calcineurin Inhibitor Mechanism

  • Tacrolimus: binds FKBP-12 → inhibits calcineurin → ↓ NFAT → ↓ IL-2 production
  • Cyclosporine: binds cyclophilin → same downstream effect
  • ↓ T cell activation
  • Nephrotoxic (↓ renal blood flow), neurotoxic, hypertensive

301.3.1.3 CAV Pathobiology

  • Immune-mediated endothelial injury
  • T-cell + B-cell roles
  • Diffuse intimal hyperplasia + accelerated atherosclerosis
  • CMV plays role
  • Reversal not possible; slow progression possible

301.3.2 Recent Trials & Updates

301.3.2.1 MOMENTUM 3 (2017, 2022, 2024)

  • N = 1028 advanced HF
  • HeartMate 3 vs HeartMate II
  • HM3: less pump thrombosis, less stroke, similar/better survival
  • 5-year survival ~ 75%
  • Established HM3 as standard

301.3.2.2 DanGER-SHOCK (2024)

  • Impella in cardiogenic shock from STEMI
  • Improved survival vs standard
  • Practice-changing

301.3.2.3 ARREST (2020) — ECMO for Refractory VF

  • ECMO + early VA-ECMO improved survival
  • Select centers

301.3.2.4 EOLIA (2018) — VA-ECMO for Severe ARDS / Shock

  • Marginal benefit; depends on selection
  • ECMO availability + experience matters

301.3.2.5 IMPELLA-Reduced Mortality in Cardiogenic Shock (DanGER-SHOCK 2024 update)

  • Specific population
  • Risk-benefit balance

301.3.2.6 Heart in a Box (Organ Care System, OCS)

  • Ex-vivo perfusion of donor heart
  • Extended ischemic time
  • DCD (donation after circulatory death) hearts now possible
  • DCD heart transplant programs expanding

301.3.2.7 Xenotransplantation 2022-2024

  • David Bennett 2022: 60 days
  • Lawrence Faucette 2023: 40 days
  • Multiple causes of death (rejection, porcine CMV)
  • Future: improved gene edits, better immunosuppression

301.3.2.8 Cell-Free DNA Monitoring

  • Donor-derived cfDNA in recipient blood
  • ↑ Indicates rejection
  • Less invasive than EMB
  • Practical clinical use emerging

301.3.2.9 iPS-Derived Cardiomyocyte

  • BIOSTAR-CMS (Japan)
  • Sheets of cardiomyocyte transplanted onto epicardium
  • Early phase
  • Hope for HF reversal

301.3.3 High-Yield Specialist Points

301.3.3.1 Heart Transplant Operative Pearls

  • Bicaval anastomosis (modern) vs biatrial (older)
  • Reduced AF + atrial dysfunction with bicaval
  • Pulmonary vein left in donor heart (none reimplant)
  • Phrenic + vagus nerves preserved (allows future Holter assessment)

301.3.3.2 Bridge to Transplant Strategies

  • LVAD bridges most patients now
  • Longer waiting times pushed development
  • DCD donor hearts expanding pool
  • Heart-only allocation algorithms revising

301.3.3.3 LVAD Optimization

  • Speed (RPM) setting
  • Continuous flow → low pulsatility
  • Right ventricular support critical
  • Anticoagulation: warfarin + ASA
  • INR target 2-3
  • Recent DOACs trialing for HM3 (less bleeding)

301.3.3.4 LVAD Aortic Regurgitation

  • Develops in 30% over years
  • Closed loop in LVAD → AR worsens with low pulsatility
  • Surgical or transcatheter (rare) treatment
  • HM3 less likely than older devices

301.3.3.5 Right Ventricular Failure Post-LVAD

  • ~ 20% develop RV failure
  • Risk factors: severe pre-op RV dysfunction, low CI
  • Treatment: inotropes, pulmonary vasodilators, RVAD
  • BiVAD consideration

301.3.3.6 Heart Transplant + Pregnancy

  • Possible but high-risk
  • Counseling about CAV progression
  • Immunosuppression considerations (mycophenolate teratogenic — switch to azathioprine)
  • Multidisciplinary planning

301.3.3.7 Pediatric Transplant

  • Indications: congenital heart disease, cardiomyopathy
  • Donor scarcity
  • Long-term challenges (CAV, renal, malignancy)

301.3.3.8 Multi-Organ Transplant

  • Heart-kidney (CKD ESRD)
  • Heart-liver (hepatic injury from HF)
  • Heart-lung (Eisenmenger, severe PH)
  • Specialized centers

301.3.3.9 Future of Cardiac Transplant

  • DCD donors expanding
  • Xenotransplantation (pig hearts, 10+ gene edits)
  • iPS-derived cardiomyocytes
  • CRISPR / gene therapy for genetic cardiomyopathies
  • Improved immunosuppression (CAR-T to clonal expansions, antibody-targeted)

301.3.4 Pearls

  • Heart transplant indications: refractory HF NYHA III-IV + EF < 25% + optimal therapy
  • MCS hierarchy: IABP → Impella → Tandem Heart → VA-ECMO → LVAD
  • HeartMate 3 (MOMENTUM 3): 5-yr survival ~ 75%; less thrombosis + stroke than HM2
  • Immunosuppression: tacrolimus + MMF + prednisone; mTOR inhibitor for CAV
  • CAV: top late cause of death; annual angiography; statin + ASA + mTOR
  • EMB rejection surveillance + AlloMap + cfDNA monitoring
  • Post-transplant complications: CAV, HTN, DM, infection, CMV/PJP, malignancy, renal (CNI)
  • Xenotransplantation 2022-2024: pig hearts gene-edited; early days
  • DCD heart donors + Heart in a Box expanding donor pool