LVAD and heart transplantation

What is a normal HR response to activity post heart transplant?

elevated resting HR, blunted HR response for first 5-10 minutes of exercise

Which is NOT a sign/symptom of transplant rejection?

decreased exercise tolerance

Which of the following complications is a leading cause of mortality for patients with an LVAD?

1. GI bleeding

2. infection

3. HF

4. neurologic symptoms

infection

what are indications for heart transplantations?

1. End-stage heart disease

2. Poor quality of life

3. NYHA class III-IV AHA stage D heart failure despite maximal therapy

what are the implantable devices MS, CRT-D, IABP?

MCS - mechanical circulatory support

CRT-D - cardiac resynchronization therapy

IABP - intraaortic balloon pump

what are absolute contraindications to heart transplantations?

1. Active or recent solid organ or blood malignancy within 5 years

2. Current or recent (within 6 months) abuse of tobacco, alcohol, or other active substances abusers

3. HIV positive with h/x of primary central nervous system lymphoma, visceral Kaposi sarcoma, or no active/prior opportunistic infections

4. Systemic lupus erythematosus, sarcoid, or amyloidosis that has multisystem involvement and still active

5. Irreversible renal or hepatic dysfunction

6. Significant obstructive pulmonary disease (FEV1 < 1L/min)

7. Fixed pulmonary HTN

8. Pulmonary artery systolic pressure >60 mmHg

9. Mean transpulmonary gradient >15 mmHg

10. Pulmonary vascular resistance >6 Wood units

11. Severe symptomatic cerebrovascular disease

12. Acute or fulminant HBV or HCV infection

what are wood units?

- system to measure pulmonary vascular resistance using increments of pressure

- subtract pulmonary capillary wedge pressure from mean pulmonary arterial pressure and dividing by cardiac output in L/min

what are relative contraindications to heart transplantations?

1. Age >70

2. Active infection (except device-related infection in VAD recipients)

3. Active peptic ulcer disease (PUD)

4. Severe diabetes mellitus with end organ damage or poor glycemic control

5. Severe PVD (if it limits rehab and revascularization is not a viable option)

6. Symptomatic carotid stenosis

7. ABI < 0.7

8. Uncorrected abdominal aortic aneurysm > 6cm

9. Morbid obesity (BMI >35 kg/m2) or cachexia (BMI < 18 kg/m2)

10. Creatinine > 2.5 mg/dL or creatinine clearance < 25 mL/min

11. Bilirubin >2.5 mg/dL, serum transaminases >3X, INR >1.5 off warfarin

12. Severe pulmonary dysfunction with FEV1< 40% normal

13. Recent pulmonary infarction within 6-8 weeks

14. Difficult-to-control HTN

15. Irreversible neurologic or neuromuscular disorder

16. Severe cognition-behavioral disabilities or dementia

17. Insufficient social supports to achieve compliant care

18. Poor nonadherence with drug regimes

19. Heparin-induced thrombocytopenia within 100 days

what are the steps for heart transplantation candidacy?

1. Referral to transplantation center by primary physician

2. Transplantation center evaluation

3. Transplantation team evaluation

4. If accepted, medical profile placed on national patient waiting list for organ transplantation maintained

5. Candidate from waiting list is matched with donor's characteristics

6. Computer rank orders waiting list according to organ allocation policies

If pt referred to transplantation center, the center must:

evaluate pt to be accepted onto transplant list at the center

what does the heart transplantation center review prior to admitting a pt onto the transplantation list?

1. Lab tests: blood type, panel-reactive antibody (PRA), flow cytometry, ABGs, CBC, PT/INR, Hemoglobin A1C, basic metabolic panel, liver function testing, NT-pro BNP, urinalysis, BUN, creatinine, chest radiograph, sputum culture, infectious serology and vaccination

2. Cardiac assessment: CPXT, 12-lead ECG, ECG, MUGA-scan, cardiac catheterization, coronary angiography, cardiac biopsy

3. Pulmonary assessment: PFTs, V/Q scan

4. Other: bone density scan, frailty assessment, CT or HRCT, GI endoscopy (>50 y/o)

what is the the role of the transplantation coordination, physician, PT, dietician, social worker, and psychologist in heart transplantation evaluations?

Transplantation coordinator: oversees eval process

Physicians: PMH, nature and progression of disease, social history, prior surgery, meds, physical exam

PT: exercise tolerance test and prescription, MSK assessment, cough/mucociliary clearance, frailty assessment

Dietician: body weight, caloric intake

Social worker: psychosocial assessment

Psychologist: psychological testing

what are you evaluating for regarding the pts emotional/mental state throughout the heart transplantation process?

- Emotional reaction to transplantation process evaluated during each stage

- Coping style when waiting may predict aspects of quality of life (better = optimistic)

- Caregiver's stress and coping style

how does UNOS prioritize patients for cardiac transplantations?

- Compatibility: blood type, height, weight, other medical factors with computer system determining order candidates will receive offer

- Medical urgency considered for prioritization of hearts (urgency status assigned)

- Pediatric status also considered for prioritization of hearts

- Geography: transport time of organ needs to be short

- Right-sized organ

what is the max organ preservation time for hearts?

4-6 hours

what are key factors to determining urgency status?

1. Implanted device to replace or stimulate circulation (total artificial heart or VAD)

2. Receiving other support for circulation or breathing (ECMO or IABP)

3. Medication to stimulate heart function

4. Life-threatening irregular heart function (tachycardia, fibrillation, arrhythmia)

5. Need one or more other organ transplants (heart-lung, heart-liver)

what factors give pts a higher priority for heart transplantations?

1. if pt is on one or more advanced therapies (ECMO, VAD, or artificial heart)

AND/OR

2. pt has difficult to control, life-threatening condition (ventricular arrhythmia, tachycardia or fibrillation)

3. if current treatment complicated by infection or clotting and/or if treatment requires pt to stay in hospital → higher status than those not having complications or able to leave hospital

what are the 4 surgical techniques for heart transplantations?

1. heterotopic

2. total transplantation (orthotopic)

3. biatrial

4. bicaval

what is the heterotopic surgical technique?

- aka "piggyback" technique

- performed less frequently than orthotopic

- mismatching of size between donor and recipient may warrant

- new heart can act as an assistive device if complications arise

- recipient's heart left in place and donor heart connected to right side of chest

what is the total transplantation (orthotopic) surgical techniqiue?

- complete excision of recipient atria + complete AV transplantation + separate bicaval and pulmonary venous anastomoses

- native heart removed and replaced by donor organ in same anatomic location as original heart

- infrequently used

what is the biatrial surgical technique?

- used for orthotopic heart transplantation

- leaves recipient SA node intact to avoid need for venous anastomoses; SA node functional through collateral bronchial circulation and innervation to atrial remnants

- donor heart's SA node is denervated and operates independently of recipient's → two separate P waves on ECG

what is the bicaval surgical technique?

- sewing separate caval anastomoses

- improved atrial function, lower rate of post-op arrhythmias, decreased need for permanent pacing, decreased tricuspid regurgitation

what is the main medication given to heart transplantation pts and what is its function?

Immunosuppressive agents --> reduce normal immune system's response to foreign tissue

what medication(s) are given to heart transplantation pts in stage 1? what is the name of this stage?

"induction agents" --> given at time of transplantation

1. Strong dose immunosuppressive

2. High dose corticosteroid (methylprednisolone)

what medication(s) are given to heart transplantation pts in stage 2? what is the name of this stage?

"maintenance agents" --> may be part of daily meds

1. Calcineurin inhibitor

2. Antiproliferative agent

3. Corticosteroids

what medication(s) are given to heart transplantation pts in stage 3? what is the name of this stage?

"rejection treatement"

1. Strong doses immunosuppressants

Acute cellular rejection occurs in ______ of heart transplant patients in first year after transplant

more than 25%

what are common immunosuppressive induction agents for transplantation?

1. Alemtuzumab

2. Antithymocyte globulin

3. Basiliximab

4. Muromonab

what are common immunosuppressive maintenance agents for transplantation?

1. Corticosteroids

2. Calcineurin inhibitors

3. Antiproliferative agents

4. Target of rapamycin (TOR) inhibitors

what are common immunosuppressive rejection treatment agents for transplantation?

1. Alemtuzumab

2. Antithymocyte globulin

3. Intravenous immunoglobulin (IVIG)

4. Muromonab

5. Corticosteroid

6. Rituximab

what are HLA antibodies?

human leukocyte antigen antibodies --> proteins that can be found in pts blood that can interfere with success of transplant

what are changes after heart transplantation surgery?

1. Denervation occurs with possible reinnervation

2. Delayed reaction to stimulus of activity → emphasis on warm up and cool down

3. Decreased HR response to activity → RPE or ventilatory response should be used

4. BP should be monitored (HTN is significant concern d/t possibility of ischemia)

5. Avoid long periods of isometrics and position pt correctly

6. VO2 max improves after heart transplantation, but still well below predicted values

what are differences in HR, HR elevation from rest, HR response to activity, and initial CV response to exercise between a normal heart and a denervated heart?

Normal Heart:

1. HR: 60-100 bpm

2. HR elevation from rest: up to 120 bpm (parasympathetic withdrawal); >120 bpm (sympathetic system)

3. HR response to activity: immediate HR increase

4. Initial CV w/ exercise: immediate CO increase

Denervated Heart:

1. HR: can increase to 90-110 bpm

2. HR elevation from rest: HR increases after 5 min d/t catecholamines

3. HR response to activity: delayed HR increase

4. Initial CV w/ exercise: HR does not change

what are differences in peak HR with exercise, SV, LVEF, SBP, DBP between a normal heart and a denervated heart?

Normal Heart:

peak HR with exercise: increase 10 bpm per MET

SV: 70 mL

LVEF: 50-65%

SBP: 7-10 mmHg per MET

DBP: rises gradually with exercise (<10 mmHg), remains the same, or drops slightly (<10 mmHg)

Denervated Heart:

peak HR with exercise: 70-80% of normal

SV: lower

LVEF: lower

SBP: at rest = same or higher; exercise peak = reduce to 80% of normal

DBP: at rest = elevated; exercise = increases abnormally or may decline (>20 mmHg)

what pulmonary values are changed after heart transplantation?

1. VO2max

2. Ventilatory threshold

3. Anaerobic threshold

4. Minute ventilation

5. Lung volumes and capacities

what are differences in VO2max, ventilatory threshold, anaerobic threshold, minute ventilation, and lung volumes/capacities after heart transplantation?

1. VO2max: 50-70% of gender and age-matched norms

2. Ventilatory threshold: 2.5 METs

3. Anaerobic threshold: reduced

4. Minute ventilation: Ventilatory efficiency (VE/VCO2) steadily improves approaching normal values 6-12 months post-transplantation

5. Lung volumes and capacities: FEV1 improves

what is included in the PT exam prior to heart transplantation surgery?

1. Submaximal treadmill or cycle ergometer testing, 6MWT

2. Chest ROM

3. balance, strength, gait, mobility deficits

7. pacing, energy conservation education

8. monitoring of vitals

9. frailty assessment

VO2max < 14 mL/kg/min =

VO2max > 14 mL/kg/min =

(in context of prior to heart transplantation)

VO2max < 14 mL/kg/min = higher risk of death, refer for transplantation

VO2max > 14 mL/kg/min = transplantation may be able to be deferred

what is frailty prior to heart transplantation associated with?

associated with postoperative complications, poor outcomes, and poor quality of life

how is frailty defined? what are 2 scoring tools used?

by 3 of 5 possible symptoms:

1. Unintentional weight loss of >10 lbs within a year

2. Sarcopenia

3. Fatigue

4. Slow gait speed

5. Reduced physical activity

--> Frailty Index (FI) and Fried Frailty Phenotype (FFP)

what are the benefits of pre-op rehab? what is included? when does it typically begin?

1. Training effects from long-term rehabilitation programs can be made

2. Training effects mainly peripheral adaptations providing functional and exercise capacity improvements

3. May also help with survival while on waiting list

--> Includes: education, CV endurance training, MSK strength and flexibility training, breathing retraining

--> Typically begin in formal cardiac rehab program (home or community exercise program)

when does acute post-op inpatient rehab begin?

Evaluated in ICU when medically stable --> 12-24 hours after surgery

what are considerations for the acute post-op inpatient eval?

1. Protective isolation observed (PT and pt)

2. Tubes and wires = intubated and mechanically ventilated; meds through IV lines; chest drainage tubes; endocardial pacemaker wires; urinary catheter; monitoring devices

3. STERNAL PRECAUTIONS!

what does the acute post-op inpatient PT exam focus on?

1. Impaired gas exchange

2. Airway clearance

3. Effects of prolonged static positioning during surgery

4. Pain

5. Mobility restrictions

what are the goals of acute post-op inpatient PT?

1. Optimize pulmonary hygiene and chest wall mechanics to wean from ventilator and supplemental O2

2. Improve strength and ROM in upper extremities and thoracic region

3. Improve exercise tolerance through ADLs and exercise at low to moderate intensity

what values at rest would indicate a pt is not appropriate for therapy at that time (post transplantation)?

HR > 120 BPM

SBP > 190 mm Hg

DBP > 110 mm Hg

ECG abnormalities that impair perfusion

RPE > 13/20 or 4/10 (somewhat hard)

what values would indicate that you should terminate therapy (or if these values aren't reached, you may progress)?

HR ↑ > 40 BPM above resting level

SBP ↑ > 40 mm Hg with exercise

SBP ↓ > 10 mm Hg below resting level with exercise

DBP ↑ > 15 mm Hg with exercise

ECG abnormalities worsen and impair perfusion

RPE increases to ≥ 15/20 or 5/10 (hard) with exercise

what values (at rest and/or with exercise) would indicate that you should terminate therapy?

Dyspnea index > 15

Excessive fatigue

Vertigo

Claudication

Mental confusion or dizziness

typically, how long is acute care stay post heart transplantation?

1-2 weeks

once the pt is moved out of the ICU, what should treatment focus on?

1. Achieving independence with mobility and ADL tasks

2. Increasing endurance

3. Strengthening proximal muscle groups

4. Weight-bearing exercises

5. Education on safety, correct performance of exercises and activity, sternal precautions, self-monitoring of heart rate and RPE, aerobic exercise guidelines, signs and symptoms of rejection or other complications

what is the leading cause of death within the first 30 days after transplantation? what is the second leading cause?

1. primary graft failure or failure of allograft

2. acute rejection and infection (bacterial infection most common)

what is acute rejection?

presence of preformed antibodies or infiltrates of mononuclear cells, which lead to myocyte necrosis; donor organ unable to maintain cardiac output

when is acute rejection suspected vs confirmed?

suspected when exhibiting s/ss of exercise and activity intolerance

confirmed with endomyocardial biopsy

how can you reverse acute rejection?

by increased dosage of immunosuppressive medication

what are s/s of acute rejection post-transplantation?

1. Low grade fever

2. Increase in resting BP

3. Hypotension with activity

4. Myalgia

5. Fatigue

6. Decreased exercise tolerance

7. Ventricular dysrhythmias

8. Dyspnea

9. Weight gain due to water retention

10. Decreased urine output

when does post-op outpatient rehab for transplantation begin?

Begins after discharge from hospital and continues for ~6 weeks

what is the gradual exercise testing protocol for post-transplantation pts?

1. Incremental treadmill test: of 1 MET or less every 30 sec-1 min OR 1-2 METs per 2-3 min stage (modified Naughton)

2. Stationary cycle testing: 10-15 W/min or 25-30 W/2-3 min

what cannot be used to detect exercise test endpoint with post-transplantation pts?

angina due to denervated heart

what training range is not appropriate for post-transplantation pts and why? what should be used instead?

- HR based training range is NOT appropriate d/t denervated myocardium - use Borg RPE, MET level, oxygen saturation, other limiting symptoms

what are special considerations for outpatient exercise prescription for post-transplantation pts?

1. D/t delayed HR response, longer warm-up and cool-down periods needed

2. Immunosuppression therapy can lead to bone loss, DM, and HTN (aerobic and resistance training can help manage these)

3. HIIT has been used with positive results (work/rest intervals similar to those for HF, but HR not used to guide intensity)

4. ROM and work rate of activities and exercises using upper limbs should be restricted for up to 12 weeks d/t sternotomy

what is the FITT dosing for aerobic exercise prescription post-transplantation?

F: 3-5 days/week

I: RPE 11-14 on 6-20 scale or talk test ONLY!

T: progressively increase to 20-60 min/day

T: treadmill or free-walking, stationary cycling, dual action stationary bike

what is the FITT dosing for resistance training prescription post-transplantation?

F: 1-2 non-consecutive days/eek

I: begin at 40% 1-RM for upper body, 50% 1-RM for lower body - gradual increase to 70% 1-RM over weeks-months

T: 1-2 set, 10-15 reps each exercise

T: weight machines = best; dumbbells, elastic bands, body weight

what is the FITT dosing for flexibility training prescription post-transplantation?

F: ≥2-3 d/wk; daily most effective

I: tightness/slight discomfort

T: 10-30 sec hold (static); 2-4 reps each exercise

T: static, dynamic, and/or PNF stretching

what are other post-transplantation complications that can occur in outpatient rehab?

1. Chronic rejection (develops as form of coronary atherosclerosis)

2. Cytomegalovirus (CMV) infection

3. Renal dysfunction

4. HTN

5. Neuromuscular dysfunction

6. Steroid myopathy

7. Pleural effusion

8. T2DM

9. Osteoporosis

10. Hyperlipidemia

11. Anemia

12. Malignancy

13. GI complications

in a 3-5 year period post-transplantation, what are the most common causes of death?

- malignancy

- cardiac allograft vasculopathy

- renal failure

why might a pt not be suitable for heart transplantation?

1. Not meeting criteria for organ system failure

2. Presence of contraindications

3. Unable to meet psychosocial requirements

4. Decreased overall benefits for patient from transplantation

5. Pt opted for more conservative surgical or medical management

what is the ideal alternative therapy for pts that are not suitable for heart transplantation?

mechanical circulatory support devices (MCSDs) or home pharmacologic management

what are examples of MCSDs? which is the most common?

- Left, right, or bi-ventricular assist devices

- Total artificial heart (TAH)

- LVAD most common

what are the benefits of IV inotropic therapy?

1. Improve CO and systemic perfusion

2. Reduce myocardial oxygen consumption

3. Enhance coronary perfusion

4. Slow rapid HR

5. Restore baroreceptor function

6. Reverse neurohumoral activation

7. Restore cardiac size and shape

8. Promote cardiac and vascular repair

9. Enhance survival

what are common IV inotropic agents?

dobutamine and milrinone

what is a VAD?

- implantable, electrically powered device

- provides permanent support of systemic circulation

when does Medicare cover a VAD>

for pts who are not transplantation candidates or with <2-year life expectancy with NYHA class IV heart failure

what is the most common device used as a "bridge" to transplantation?

LVAD

what is a pVAD?

- percutaneous VAD

- temporary

- before LVAD placed

when are LVADs used?

for pts with end-stage HF with reduced ejection fraction (HFrEF)

what are indications for durable medical support?

1. LVEF <25%

2. NYHA IIIb-IV symptoms for at least 45 of last 60 days

3. Refractory HF symptoms despite optimal medical and device therapy

4. VO2max < 14 mL/kg/min

5. Continued need for IV inotropic therapy d/t symptomatic hypotension, worsening end organ function, or persistent pulmonary edema

6. IV inotropic medication use for ≥ 14 days

7. IABP support for ≥ 7 days

8. CO <2L/min

what LVADs are approved by the FDA?

1. HeartMate II

2. HeartWare ventricular assist device system

3. HeartMate 3

FDA-approved LVADs are __________ pumps

continuous (non-pulsatile) flow pumps

how are LVADs implanted?

via sternotomy or thoracotomy

how long do LVAD batteries last? what does the LVAD external controller show?

- batteries last up to 12 hours

- controller show battery charge, LVAD speed, flow, power, pulsatility index

LVAD speed is set to ensure what?

set to ensure adequate left ventricular unloading

what complications can arise if LV unloading is too little or too much?

Too little unloading -> pulmonary edema and HF

Too much unloading -> suctioning -> hypotension and arrhythmias

optimal LVAD function is based on what 2 principles?

1. Preload dependent

2. Afterload sensitive (cannot have too much pressure to work against)

what are the survival rates on continuous flow LVAD?

1 year = 83%

3 years = 63%

5 years = 46%

what should be included in the pt history assessment?

1. Recent device parameters and alarms

2. Symptoms of driveline infection

3. HF symptoms

4. ICD shocks

5. Signs of hemoglobinuria (can indicate LVAD thrombosis)

5. Overt bleeding (hemoglobinuria, melena)

what are considerations for the physical examination of pts with LVADs?

1. Frequently have no palpable pulse (or faint and intermittent)

2. BP may not be measurable by auscultation

3. "Hum" of LVAD should be heard on auscultation

Target mean arterial pressure (MAP) for pts with LVAD =

what MAP may warrant therapeutic intervention?

60-80 mmHg

>90 mmHg may warrant therapeutic intervention

why might pts with LVAD not have a palpable pulse?

due to high levels of sympathetic nerve activity from baroreceptor unloading

Sustained ventricular tachycardia or ventricular fibrillation in pts with VAD generally precipitate:

worsening R HF --> prompt attention needed

what lab values are tested to evaluate for anemia, anticoagulation goals, and hemolysis?

1. INR (anticoagulation)

2. Plasma-free hemoglobin >40 mg/dL

3. Lactate dehydrogenase (LDH)

4. Urinalysia (hemoglobulinuria)

what imaging tests are commonly seen with LVADs?

1. Periodic echocardiography

2. Contrast-enhanced gated CT scan

3. PET imaging with F-18 fluoro-2-deoxyglucose

what do periodic echocardiographies assess?

- LV function

- filling pressures

- inflow cannula position

- orientation

- obstruction

- adequacy of LV unloading

- aortic valve opening

- aortic insufficiency

what do Contrast-enhanced gated CT scans assess?

1. Inflow cannula malpositioning

2. Outflow graft thrombosis, kinking, narrowing

what do PET imaging with F-18 fluoro-2-deoxyglucose assess?

1. Presence and extent of infection if infection suspected

what is included in the medical management of pts with LVADs?

1. HF therapy

2. Management of HTN

3. Antithrombotic therapy

what medical management is used for volume overload?

diuretics

what medical management is used for HTN?

Angiotensin converting enzyme inhibitor or angiotensin II receptor blocker and/or beta blocker

what medical management is used to decrease need for potassium repletion in patients with preserved renal function?

aldosterone antagonist

what is the preferred management for HTN?

HF medications

For those with continuous flow LVADs, mean arterial BP goal is:

≤ 80 mmHg