Cardiac Transplant Flashcards
What is the first criteria you look at to determine eligibility for transplant
Transpulmonary gradient
How do you calculate transpulmonary gradient?
How do you calculate Woods units?
TPG = mean PAP - PCWP
TPG in Woods = mean PAP - PCWP/CO
What % of transplants have previously had LVAD?
up to 50%
What are the absolute contraindications to transplant?
Absolute contraindications
Systemic illness with a life expectancy 2 y despite heart
transplantation, including
Active or recent solid-organ or blood malignancy within 5 y
AIDS with frequent opportunistic infections
Systemic lupus erythematosus, sarcoid, or amyloid with active
multisystem involvement
Irreversible renal or hepatic dysfunction in patients considered for only heart transplantation
Significant obstructive pulmonary disease (FEV1 1 L/min)
Fixed pulmonary hypertension
Pulmonary artery systolic pressure 60 mm Hg
Mean transpulmonary gradient 15 mm Hg
Pulmonary vascular resistance 6 Wood units
What are the relative contraindications to transplant?
Age Pulmonary Hypertension - >5 woods units Osteoporosis - > 2 SD below normal Obesity >35 BMI Diabetes - with end organ damage GI disease - active peptic ulcer disease until treated, active diverticulitis Technical issues - difficulties with surgery Peripheral and cerebral vascular disease Renal dysfunction Cr > 200 Amyloidosis Cardiac disease
Name 4 heart transplant techniques
Biatrial (Lower-Shumway) - issue is TR
Bicaval technique
Total orthotopic technique
Domino technique (heterotopic)
What are the absolute and relative indications for VO2max in transplant?
relative <14 (12 if on BB)
absolute <10
What is the sequence of anastomosis in heart transplant?
Usually from posterior to anterior structures
Left atrium -> IVC -> SVC -> PA -> Aorta
To reduce ischemic time
do Left atrium then Aorta and take cross clamp off
But can get coronary sinus blood during sowing of right sided anastomoses
Left atrium -> IVC -> PA - > Aorta -> cross clamp off -> SVC if you feel that IVC will be challenging with cross clamp off
Where is the donor cardiac transplant cut?
IVC - cut at the confluence between the RA and IVC. To identify it, make an anterior cut on the IVC and find the pink of the RA and the white of the IVC. There is no reason to take IVC
PA - must leave 5mm cuff between the posterior commissure of the PA and the bifurcation of the PA. Sometimes there is very little distance between the two, as little as 1cm
LA - lung surgeons need cuff around pulmonary veins, make sure to leave 5mm cuff around pulmonary veins. The most critical part is leaving the right pulmonary vein cuff at least 5mm for the lung team. When cutting the left side, you cut half way between the coronary sinus and the left pulmonary veins.
What is the Maastricht Classification for Donation after Cardiac Death?
1 - Dead on arrival - Uncontrolled
2 - Unsuccessful resuscitation - Uncontrolled
3 - Awaiting cardiac death after withdrawal of life sustaining therapies - Controlled
4 - Cardiac arrest in brain dead donor - Either
5 - Unexpected arrest in ICU patient - Uncontrolled
an alternative version does not have class 5
another alternative version states that category 5 is Euthanasia and is controlled (this is the Belgian/French modification)
What is total ischemia time?
For donor after brain death, Warm Ischemia Time + Cold Ischemia Time.
Donor warm ischemia time = Time from withdrawal of life support to heart removal and initiation of cold storage.
Cold ischemic time (ideally 4hrs) = initiation of cold cardioplegia, donor cross-clamp time and cold storage to removal from cold storage.
Graft warm ischemia time = time from removal from cold storage to reperfusion from recipient CPB circulation after implantation.
What’s the donor management targets - per Papworth criteria?
Conventional:
CVP 6-10mmHg
pH 7.35-7.45
PaO2 80-100mmHg or SpO2 92-100%
PaCO2 35-45 mmHg
Hct >30 or Hb >100
MAP >60 (60-80mmHg ideal)
HR 60-120 bpm in NSR
Temperature 36-37.5 C
If LVEF <45% - Papworth Criteria:
Hormones –
Insulin
DDAVP (Vasopressin)
T3
Methylprednisolone
Hemodynamics –
MAP >60mmHg
PCWP 8-12mmHg
CI >2.4
CVP 4-12mmHg
SVR 800-1200
LVSWi >15
Define apnea test. What are criteria for neurological death?
Apnea test:
PaCO2 ≥60 mmHg (and ≥20 mm Hg above the pre-apnea test level) and pH ≤7.28.
Usually within 10-15 minutes.
Neurological death criteria:
1. Evidence of massive unrecoverable brain injury
No other reason for somnolence. No other drugs, or hypothermia, severely abnormal electrolytes.
- Comatose state: No purposeful movements, not awake.
- Absence of motor responses to painful stimuli
- Absence of Brain Stem Reflexes: Neuro death criteria (addition to Apnea test):
Spinal cord reflexes exempt.
Brain-stem reflexes – Cough reflex, Cold calorics (Vesticulo-ocular), Corneal reflex, Pupillary response, Gag reflex, Doll eyes (no eye movement when head is turned aka Oculocephalic reflex, this was removed in the Canadian guidelines in 2023)
Additional tests to rule out blood flow to the brain – radionucleotide angiography or cerebral angiography.
What are common immunosuppression maintenance agents?
4 categories:
Calcineurin inhibitor (CNI) (activate NFAT - upregulate IL-2) – Tacrolimus
Anti-metabolite (cell growth and division) – MMF
Corticosteroids – Prednisone
Proliferation signal inhibitor (PSI) (Inhibit the mammalian target of rapamycin) – Sirolimus
Standard therapy:
Tacrolimus + MMF + steroids
Substituting therapy?
CAV – CNI to PSI
Renal failure – CNI to PSI
Cancer – Lower immunosuppression intensity. And add PSI
What are common induction agents?
Anti-thymocyte globulin (CD52; T/B-cell depletion);
Aletuzumab (CD52; T/B-cell depletion);
Basiliximab (IL-2R antagonist)
No survival benefit; no difference in outcome between types of induction agents used
Advantage:
May decrease incidence of rejection
Can extend CNI free period for pts with renal failure
May slow CAV
Disadvantage:
Increase risk of infection
Increase risk of malignancy
What are common de-sensitizing methods?
Indication:
cPRA 50-79% and previous positive virtual crossmatch
Status S (cPRA >80%)
Status 4
Protocol:
IVIG (reduces antibody) monthly and Rituximab (CD20; reduces B-cell) single dose
If no reduction in antibody after 3 months: consider
Boretezomib (reduces plasma cell) or Eculizumab (complement).
PLEX (plasmapheresis) for short-term antibody depletion perioperatively.
What is acute cellular rejection grades? Timing?
ACR: also known as Type 2a rejection
0R: no rejection;
1R: interstitial infiltrate with 1 foci of myocyte damage;
2R: 2 or more foci of myocyte damage;
3R: diffuse interstitial infiltrate with multifoci myocyte damage with edema, hemorrhage, or vasculitis
Timing:
3-6 months
Treatment:
0R and 1R – no treatment.
2R – pulse oral steroids.
2R symptomatic and 3R – pulse IV steroids.
If graft function affected – ATG (rabbit over horse).
What is antibody-mediated rejection grades? Timing?
AMR: also known as Type 2b rejection
pAMR0: negative histo/immune
pAMR1(H+): isolated histo finding – capillary injury, some endothelial swelling
pAMR1(I+): isolated immuno finding – C4d+ and C68+
pAMR2: both histo and immuno finding
pAMR3: both histo/immuno finding with interstitial hemorrhage, marked edema & cell karyorrhexis (and pyknosis)
Timing:
Weeks to years. 50% by 15 years
Treatment:
pAMR0 = routine surveillance.
pAMR 1-3 with allograft dysfunction or symptoms = Treat with ATG, Bortezomib, Rituximab, IVIG, Plasmapheresis
Donor-specific antibodies (but no pAMR and negative biopsy and no allograft dysfunction) = Increased surveillance
Antimicrobial prophylaxis post transplant? And the three immunizations post-transplant?
CMV –
Valganciclovir – for 3-6m for D+/R-, R+ with induction; or 3m for R+ no induction
P. Jerovicii –
Septra – for 1 year
Skin cancer –
High-risk population screening
Immunizations –
No live vaccines, like MMR/Rubella
Give flu vaccines
Give pneumococcal vaccine
Give COVID-19 vaccine
What is CAV? What are risk factors?
Cardiac allograft vasculopathy – accelerated form of CAD. Characterized by concentric fibrous intimal hyperplasia along the coronary length. Affects the microvascular system as well.
Risk factors –
Shared with CAD:
- Hypercholesterolemia
- Diabetes
- Hypertension
- Smoking
Unique to CAV:
- Acute rejection episodes
- Increased ischemia time
- Ischemia-reperfusion injury
- CMV infection (infects vascular endothelial cells, increasing endothelial injury and promoting inflammatory response and hyper-fibrosis)
- Older donor age
- Use of CNI
Risk factors for malignancy?
- CMV
- Induction agents
- EBV
- High dose of immunosuppression
- Older donor age
Pros and cons of bi-caval vs bi-atrial?
Pros
Less atrial arrythmia
Less pacemaker requirement
Less AV valve insufficiency
Decrease hospital length of stay
Cons
More technically challenging/longer OR
Risk of caval stenosis
What are predictors of long-term survival after heart transplant?
Recipient age <55 years
Younger donor age
White race
Male
Lower BMI
Indicated for non-ischemic cardiomyopathy (also better for recovery on LVAD)
Annual center volume – 9 or more transplants
Shorter ischemic time <4 hours
Why not start proliferation signal inhibitors (aka mTOR) inhibitors, early? Why do we start them late?
Early PSI –
Higher rejection
Poor wound healing
Pericardial effusions
Infections
Late PSI –
Delay CAV progression
Help withdraw/wean CNI if renal failure an issue.
After cancer diagnosis, reduce maintenance therapy doses and add PSI (especially instead of MMF).
Interacts with CNI and causes an increase in level and may worsen nephrotoxicity and delay sternal wound healing
3 reasons for PSI:
Renal dysfunction: as renal sparing agent to withdrawal or minimize CNI due to renal dysfunction
CAV: delays progression of CAV (substituted for azathioprine and used in combination with cyclosporine – could be used alone?)
Anti-neoplastic: combination with tacrolimus or in place of MMF, decreases rates of treated rejection, CMV infection, and malignancy
What is the new 4S listing status? When do you consider desensitization?
4S – Highly sensitized category 4 patient cPRA>80% for heart transplant (Canadian guidelines)
5 subcategories = cPRA 100%, 99%, 98%, 97-90%, 80-89%.
Consideration of desensitization therapies –
Patients with cPRA 50-79% + previous positive virtual cross match (= missed organ)
Approach to AL and ATTR in the transplant setting?
AL (light chain):
Bortezomib-based chemo pre-transplant, then transplant. After transplant, consider autologous bone marrow cell transplant 6-12m after.
Isolated AL cardiac amyloid, per 2016 ISHLT, for highly selected patients, HTx followed by autologous stem cell transplant.
ATTR (transthyretin):
Disease-specific medication pre-transplant (tafamidis, vutrisiran, acoramidis).
Rule out extra-cardiac involvement
Consider combined heart-liver transplant to remove hepatic production of mutant protein.
ATTRwt: treated with chemotherapy and show reduction, then HTx and autologous bone marrow transplant. Most patients are elderly and not transplant candidates.
hATTR: heart only with medication or combined heart and liver transplantation may be considered
Hyperacute rejection –
Fatal due to preformed anti-HLA class I (A,B,C) antibodies.
Eliminated with virtual cross-match.
Acute cellular rejection (ACR) –
Common in first 3-6months. Warrants treatment in 10% of patients at 1yr
0R and 1R – no treatment.
Asymptomatic 2R: oral pulsed steroids (Strong recommendation)
Symptomatic 2R or any 3R: IV pulsed steroids (Strong recommendation)
ACR + graft dysfunction: Anti-thymocyte globulin – rabbit over horse (Strong recommendation)
Antibody-mediated rejection (AMR) –
Less common with longer timespan, preformed (early graft dysfunction) or de novo antibodies (late graft dysfunction)
pAMR 0 or 1 – no treatment
pAMR 2 or 3 – Treat
Any pAMR with graft dysfunction – Treat
Any pAMR with DSA – Treat
Any pAMR with symptoms – Treat
DSA with graft dysfunction (negative pAMR) – Increased surveillance
Treatment –
Combination of IV pulsed steroids, PLEX, IVIG/thymoglobulin +/- rituximab/bortezomib (Weak recommendation)
For both ACR and AMR, repeat endomyocardial biopsy at 7-14d after treatment (Strong recommendation)
What is recommended for prevention of CAV? Treatment of CAV?
CAV prevention –
Statins (Pravastatin), manage CV risk factors, CMV prophylaxis, PSI (sirolimus; everolimus), ASA and ACEi (weak)
CAV treatment –
Early – PSI (under 5 yrs), Focal CAV – PCI, CAV and Graft Dysfunction – Re-transplant
Prevention –
Younger donor, decrease ischemic time, ASA, optimize recipient RF (HTN (ACEi/CCB)/DLP/DM), pravastatin, PSI
Treatment –
Early (<5 years): PSI
Focal: PCI
Diffuse & graft dysfunction: Re-transplantation
