10. Heart Failure, Pulmonary HTN, Transplant Flashcards
Name 3 contraindications to heart transplant
- Elevated PVR
- Drug/alcohol addiction
- Active PE (resolved PE is NOT)
In a Fontan patient, is PLE or plastic bronchitis a contraindication to tranplant?
No, but they do increase risk
Most common indication for heart transplant in teenage years?
Cardiomyopathy
Most common indication for heart transplant in patients >1?
Cardiomyopathy
-Dilated, restrictive, hypertrophic, non-compaction
Most common indication for heart transplant in infants?
CHD (need has been decreasing)
Name some findings of transplant rejection
- Tachycardia
- New murmurs (MR/TR)
- Evidence of congestion (hepatomegaly, JVD, abnormal CXR)
- Gallop rhythm
What can cause a soft flow murmur in a patient early after heart transplant?
Anemia
Most common echo findings in active transplant rejection?
- New effusion
- Increased wall thickness and ventricular mass
- Increased MR/TR
- Decreases in MV TDI velocities
What is a potential complication in patients with HLHS after transplant?
Recoarctation of the aorta- may need cath for balloon angioplasty or stenting
HLHS patient s/p transplant, right arm HTN and abdominal aortic doppler with diastolic flow continuation… cause?
Re-coarctation
Contraindications to combined heart/lung transplant for pediatric patients
- Active TB
- Active malignancies
- Sepsis
- Severe systemic or neuromuscular diseases
- Multiorgan dysfunction
- Social concerns
*On ECMO at time of listing is controversial
Name 3 common indications for a heart-lung transplant
- CF
- Pulm HTN
- Eisenmenger
Transplant patient with irritability, tremulousness and seizures… which medication should you get a level to check for toxicity?
Tacrolimus
True or False: B-blockers have little effect on tacrolimus/cyclosporine levels?
True
What medications can increase tacrolimus/cyclosporine levels?
- Antifungals (fluconazole)
- Amiodarone
- Macrolides
- CCB
- Metoclopramide
What medications can decrease tacrolimus/cyclosporine levels?
- Octreotide
- Some anticonvulsants (phenytoin, phenobarbital, carbamazepine)
- Antibiotics (nafcillin, IV bactrim)
What is chronic inflammation of the bronchioles that results in fibrous deposition and ultimately obstructs airways?
Bronchiolitis obliterans
What is a form of chronic rejection in lung transplant recipients?
Bronchiolitis obliterans
What is the clinical presentation of bronchiolitis obliterans?
Non-specific… can be URI like at first, increase in exertional dyspnea, decreased daily spirometry values
Elevated exhaled NO levels and decreased mid-expiration flow rates (FEF 25 to 75) in a lung transplant patient?
Bronchiolitis obliterans
Poor prognostic indications in restrictive cardiomyopathy?
- Significant cardiomegaly
- Pulmonary venous congestion on CXR
- Elevated LVEDP
- Degree of LA dilation
What happens to TDI parameters in patients with restrictive cardiomyopathy?
Low
True or false, RAE on echo and TR murmur are poor prognostic indicators in restrictive cardiomyopathy?
False, but can be indicative of degree of RV dysfunction
What is the gold standard test to rule out rejection in transplant patient?
Myocardial biopsy
Besides myocardial biopsy, what other testing can suggest rejection of heart transplant?
- Cardiac MRI
- ECG (low-voltage QRS signals)
- BNP (trend)
- Echo
What 2 things should you consider in a transplant patient with a new-onset arrhythmia?
- Rejection
- Coronary artery vasculopathy
*Further out from transplant, likely coronary artery vasculopathy
Side effects of tacrolimus when levels too high?
- Irritability
- Tremulousness
- Seizures
Side effects of azathioprine and mycophenolate?
- Leukopenia
2. GI: Constipation, diarrhea, nausea
Side effects of sirolimus?
- Diarrhea
2. Mouth sores
Side effects of prednisone?
- Mood changes
- Increased appetite
- Increased blood glucose
- Weight gain
- Cushingoid appearance
- Osteoporosis
Familial pulmonary HTN gene?
BMPR2
What chromosome is BMPR2 found on?
2
How is the BMPR2 gene (pulm HTN) inherited?
AD (low penetrance, 20%)
TBX5
Holt-Oram (large ASD + radial anomalies)
MLL2
Kabuki
JAG1
Alagille
PTNP11
Noonan
MOA Sildenafil?
PGE-5 inhibitor-
Blocks phosphodiesterase from degrading cyclic GMP in smooth muscle cells and promotes vasodilation
Name 3 endothelin receptor antagonists
- Bosentan
- Abrisentan
- Macitentan
MOA ambrisentan?
Selective endothelin A receptor antagonist
MOA bosentan and macitentan?
Endothelin A and B receptor antagonist
What drug is used IV to restore balance of endogenous thromboxanes and prostacyclins to induce vasodilation?
Prostacyclin (prostaglanin I2)
What drug suppresses the production of prostaglandins and thromboxanes by irreversibly inactivating the cyclooxygenase enzyme
ASA
What is definitive therapy for restrictive cardiomyopathy?
Transplant
True or False: Without transplant, patients with restrictive cardiomyopathy have up to 50% mortality within 2-3 years of diagnosis of restrictive cardiomyopathy?
True
Besides transplant, what is the only medical therapy to help with symptoms in restrictive cardiomyopathy?
Limited diuresis
*Have to be cautious, patients are preload sensitive
Are ACEi helpful in restrictive cardiomyopathy?
No
Why is a liver US done as part of transplant evaluation?
Risk of long-term hepatic congestion
What should always be ruled out in patients with an elevated RVSP?
Pulmonary vein stenosis
*LAE points to ventricles/cardiomyopathy as issue versus pulmonary veins however
Dilated cardiomyopathy, on enalapril, carvedilol, spironolactone and lasix… what medication can be added if continued HF symptoms?
Digoxin
Should you start digoxin in a HF patient who is asymptomatic?
No
Which HF patients may need lower doses of digoxin?
- Renal dysfunction
- Taking carvedilol
- Taking amiodarone
In HF patients, when would you wean medications?
Only if ventricular function has improved
When can milrinone be used in HF patients in the outpatient setting?
Bridge to transplant
MOA spironolactone?
Inhibits aldosterone at distal tubule
*K-sparing, mild diuretic effect (used concurrently with loop or thiazide)
Where does acetazolamide act?
Proximal convolute tubule (carbonic anhydrase inhibitor)
Where do thiazide diuretics act?
Distal convoluted tubule (inhibit Na/Cl transport)
Where do loop diuretics act?
Thick ascending limb of loop of Henle (inhibit Cl-Na-K cotransport)
Where to Ca channel blockers act?
L-type Ca channels in heart
What agents can cause methemoglobinemia?
- Topical anesthetic agnents- Lidocaine, benzocaine, prilocaine
- Dapsone
When is dapsone used?
PCP prophylaxis in patients who can’t use Bactrim
How do you treat methmeoglobinemia?
- Stop offending agent
2. Methylene blue
How does methemoglobinemia present?
Acute hypoxia
MOA Enalapril?
ACEi- Decreases the amount of angiotensin I that is converted to angiotensin II
- Angiotensin II is a vasoconstrictor, ACEi promote vasodilation
- ACEi decrease degradation of bradykinins
- ACEi reduce production of aldosterone
What do you need to counsel females about who take ACEi?
Avoid pregnancy
What grade of rejection is defined by biopsy with intersitial and/or perivascular infiltrates with up to one focus of myocyte damage following heart transplant?
Grade 1R (mild)
What grade of rejection is defined by biopsy with 2 or more foci of infiltrate with associated myocyte damage following heart transplant?
Grade 2R (moderate)
What grade of rejection is defined by biopsy with diffuse infiltrate with multifocal myocyte damage (with or without edema, hemorrhage or vasculitis) following heart transplant?
Grade 3R (severe)
Above what rejection grade in heart transplant should be treated?
2R or greater
How is heart transplant rejection initially treated?
Pulsed steroids
True or False: Grade 1R rejection after heart transplant shouldn’t be treated
False- Decision is controversial and depends on several factors like prior biopsies, protocols at the institution and comorbidities
If familial/inherited, what is the most common pattern of inheritance in DCM?
AD- 50% risk of developing DCM for children of affected individual
*There are rare forms inherited as an x-linked or autosomal recessive pattern (often associated with neuromuscular disease or metabolic derangements)
What is the most common complication of azathioprine and mycophenolate?
Leukopenia
Besides leukopenia, what is another common side effect of azathioprine and mycophenolate?
GI: Constipation, diarrhea, nausea
What rejection medication can cause irritability and tremulousness if levels are too high?
Tacrolimus
List side effects of prednisone
0Mood changes
- Increased appetite
- Increased blood glucose
- Weight gain
- Cushingoid appearance
- Long term use associated with osteoporosis
When there is EBV mismatch between donor and recipient in heart transplant, what is done to reduce the likelihood of development of post-transplant lymphoproliferative disorder (PTLD)?
Minimize immunosuppression therapy
True or False: Post-transplant lymphoproliferative disorder is a significant cause of graft loss and death after transplant?
True
What has been shown to improve survival in the settling of PTLD following transplant?
Reduction in immunosuppression early after transplant
The majority of lymphomas after transplant are related to what?
EBV
Can someone with PTLD be listed for re-transplant?
Controversial (institution-dependent)
How is Barth syndrome inherited?
X-linked recessive
DCM or LVNC, hypotonia, proximal muscle weakess, neutropenia, short stature?
Barth
*Age and severity vary widely
What gene mutation is seen with Barth syndrome?
TAZ mutation
*Encodes Tafazzin protein
In a patient with heart failure and a dry hacking cough, what medication adjustment should be made?
Switch from ACEi to ARB
Why does ACEi cause cough?
- Mechanism not fully determined, thought to be related to increased local concentration of kinins and substance P (may induced bronchial irritation)
- May also be related to arachidonic acid pathway activation…lead to elevated levels of thromboxane and subsequent bronchoconstriction
Cough due to ACEi usually improves in what timeframe?
Within a week
True or False: ACEi induced cough has a high rate of recurrence
True- Up to 67% if second challenge of medication given
Management options for coronary artery vasculopathy following transplant?
- ASA
- Statin drug (pravastatin)
- Switching from a calcineurin inhibitor (cyclosporine, tacrolimus, pimecrolimus) to an mTOR inhibitor (sirolimus or everolimus)
Coronary angiography with areas of diffuse coronary luminal narrowing in multiple branches and biopsy with no evidence rejection after transplant?
Severe coronary artery vasculopathy
Can you do stenting for coronary artery vasculopathy following transplant?
In certain situations… typically doesn’t have long-term benefit due to high instance of re-stenosis
What is the best option for severe coronary artery vasculopathy following transplant?
List for re-transplant
What are 2 treatment options for rejection after transplant?
- Steroids
2. Plasmapheresis
True or False: Many patients with coronary artery vasculopathy following transplant get presumptive treatment for rejection
True (with hope for clinical improvement)
*This shouldn’t be done in lieu of listing for re-transplant
What should you consider in a post-transplant patient with irritability and prominent venous distention in head/neck?
SVC obstruction
*Can be seen with SVC thrombus or obstruction at SVC anastomosis
Risk for SVC obstruction following transplant increases in what 2 patients groups?
- Prior SVC intervention (Glenn)
2. Bicaval anastomosis for transplant
What % of pediatric heart transplant recipients require further intervention on SVC?
10%
What is 1st line treatment for SVC obstruction following heart transplant?
Angioplasty +/- stenting
What drug inhibits the Cl-Na-K cotransport in the thick ascending limb of the loop of Henle?
Loop diuretic (Lasix)
What is the preferred primary diuretic therapy in systolic heart failure?
Loops
What drugs inhibit Na/Cl transport in the distal convoluted tubule?
Thiazides
Where do carbonic anhydrase inhibitors (like acetazolamide) act?
In the proximal convoluted tubule
How do K sparing diuretics like spironolactone work?
Inhibit aldosterone at distal tubule
- Reduce K loss in urine
- Mild diuretic effect… usually used with loop or thiazide
What do CCB do?
Block l-type Ca channels in the heart
MOA for carvedilol?
Non-selective B blockade
Alpha blockade
MOA of metoprolol?
Selective blockade of B1
Little to no effect on B2
MOA ACEi?
Inhibition of ACE
Prevents conversion of angiotensin I to angiotensin II
What drug has direct vasodilation of arterioles with subsequent decrease in systemic resistance?
Hydralazine
What does hydralazine do to afterload, CO, filling pressure?
Decreases afterload
Increases CO
Decrease filling pressures
*Dilates peripheral arteries
What drug blocks epithelial Na channels in late distal convoluted tubule and collecting duct?
Amiloride
What is the effect of amiloride?
- Inhibits Na reabsorption from lumen in late distal convoluted tubule and collecting duct
- Reduces net negative potential of lumen of tubule (reduces both K and H excretion)
