PREP 2022 Flashcards
Absent pulmonary valve syndrome is most commonly associated with what?
ToF
Absent pulmonary valve syndrome occurs in what % of ToF?
2.5%
True or False: In absent pulmonary valve syndrome, there can be complete absence of pulmonary valve tissue or a small ridge of tissue at the valve annulus which is often hypoplastic?
True
What is the presentation of absent pulmonary valve syndrome?
Varies widely from minimal symptoms to respiratory distress/failure
What causes respiratory distress in absent pulmonary valve syndrome?
Proximal and/or distal bronchial compression
What can be done to improve respiratory distress in absent pulmonary valve syndrome?
-Prone position (reduces bronchial compression by the PAs and decreases ventilation/perfusion mismatch)
-Intubation/PPV for patients with persistent respiratory distress
How can ToF absent PV syndrome result in cyanosis?
R-L shunting at the VSD
True or False: Patients with ToF absent PV syndrome are dependent on unrestrictive mixing at the atrial level?
False
The absence of what is hypothesized to be associated with the development of absent pulmonary valve syndrome?
PDA (only rare cases where absent pulmonary valve syndrome develops with the presence of a PDA)
Respiratory distress in ToF absent PV syndrome is often the result of what?
Dilated pulmonary arteries causing bronchial compression
What can help to decrease ventilation/perfusion mismatch in ToF absent PV syndrome?
Prone positioning (moves that PAs off the airway to decrease bronchial compression)
*Patients with persistent respiratory distress may require intubation and PPV
How is the RP relationship determined?
-Draw a line at the midway point between 2 R waves
-If the P wave falls in the first half of the RR interval, it is short RP tachycardia
-If the P wave falls in the second half of the RR interval, it is long RP tachycardia
What is the differential diagnosis for a long RP tachycardia?
-Atrial ectopic tachycardia
-PJRT
-Atypical AVNRT
-Sinus tachycardia
Describe the P-waves in PJRT
Deeply negative in the inferior leads (II, III, aVF)
Describe the P-waves in sinus tachycardia?
-Normal P-wave axis and morphology (positive in I and aVF)
Long RP tachycardia with low-amplitude P waves and a biphasic P-wave in lead I… most likely etiology?
EAT- Long RP tachycardia with abnormal P-waves, but not PJRT (P-waves would be negative in II, III, aVF)
True or False: Patients with EAT can have incessant tachycardia?
True- Rate may not be significantly elevated and patients can be asymptomatic delaying diagnosis…. longer duration of tachycardia before diagnosis, greater risk of patient developing tachycardia induced cardiomyopathy
What should be done before treating EAT?
Echo- need to assess for structural abnormalities and ventricular dysfunction
What is the typical first line therapy for EAT if function is preserved?
B-blockers
After beta-blockers, what are the next medications used for EAT?
-Sotalol or Flecainide
-Amiodarone as a 3rd line agent
Besides antiarrhythmics, what can be done to treat EAT?
Ablation- Potentially curative with high success rates and low complication rates
*Should be considered 1st line if patient is adequate size (and if there is ventricular dysfunction)
Describe the RP relationship in SVT due to WPW and typical AVNRT
Short RP
What is the differential diagnosis for long RP tachycardia?
-EAT
-PJRT
-Atypical AVNRT
-Sinus tachycardia
Patients with incessant atrial tachycardia are at risk of developing what?
Tachycardia induced cardiomyopathy (more common when HR isn’t significantly elevated)
Failure to thrive, macroglossia, mild respiratory distress, cardiomegaly, hepatomegaly, mild generalized hypotonia, elevated CK and transaminases?
Classic infantile-onset Pompe
In classic infantile-onset Pompe disease, enzyme assay will shoe a severe deficiency of what?
Acid alpha glucosidase
What is a lysosomal storage disorder characterized by deficiency or complete absence of the lysosomal enzyme, acid alpha glucosidase (GAA)?
Pompe
-Also known as glycogen storage disease type II or acid maltase deficiency
What causes Pompe disease?
Autosomal recessive mutation of the GAA gene on chromosome 17q25
What does deficiency of acid alpha glucosidase result in?
Accumulation of glycogen in lysosomes and cytosol of target organs (skeletal muscle, cardiac muscle, liver)
How does Pompe disease present?
Wide spectrum of disease manifestations that vary in time of clinical onset, severity of symptoms, rapidity of disease progression and overall prognosis
What does the disease severity in Pompe correlate with?
Amount of residual GAA (alpha glucosidase) activity
How is Pompe disease calssified?
-Infantile onset
-Late onset
*According to age of initial clinical presentation
When and how does classic infantile Pompe disease usually present?
-1st 2 months of life
-Generalized hypotonia, cardiomegaly, respiratory distress, feeding difficulties, failure to thrive
What is the characteristic cardiac finding in Pompe patietns?
HCM
What causes HCM in Pompe patietns?
Deposition of glycogen into the myocardium
Besides HCM, what other cardiac findings can be seen in Pompe disease?
LVNC
What is often seen on echo in Pompe patients?
LVOTO due to HCM
What is seen on ECG in Pompe disease?
-Short PR interval
-Tall QRS complexes with increased voltages
-Increased QT dispersion
What is often seen in a later stage of infantile Pompe disease?
Progressive dilation of the ventricle
What is the natural history of Pompe disease if left untreated?
Death by 1-2 years due to cardiorespiratory failure
Patients with classic infantile Pompe disease that what % of residual GAA (alpha glucosidase) activity?
<1%
How does non-classic infantile Pompe disease present?
1st year after birth, but is associated with less severe cardiomyopathy and slower disease progression
How does late-onset Pompe disease present?
-Any time after infancy as a progressive skeletal myopathy
-Typically not associated with any cardiac manifestations
-Enzyme assay with 4-40% of residual GAA (alpha glucosidase) activity
What is the specific treatment for Pompe disease?
-Enzyme replacement therapy using recombinant human GAA (alpha glucosidase)… has been available since 2006
True or False: In infantile Pompe disease, early institution of enzyme replacement therapy has been shown to decrease LV mass, improve skeletal muscle function and prolong overall survival?
True
True or False: In infantile Pompe disease, early institution of enzyme replacement therapy improves LV voltages, QT dispersion and PR intervals on ECG?
True
True or False: In late-onset disease, enzyme replacement therapy has been shown to slow the progression of muscle weakness?
True
True or False: Pompe disease is on the newborn screening protocol in many states?
True (since 2015)
When is the best time to initiate enzyme replacement therapy in infantile Pompe disease?
First few days after birth
Severe aortic root dilation is commonly seen in what?
Connective tissue disorders like Marfan
True or False: It would be quite unusual to see a dilated LV with severely decreased LV function in the early phase of infantile Pompe?
True- can be seen at a later stage in classic infantile Pompe disease when the ventricular function deteriorates and the heart dilates
True or False: Pericardial effusion is not specifically associated with infantile Pompe disease?
True
What is a glycogen storage disorder caused by a deficiency or complete absence of lysosomal acid alpha glucosidase?
Pompe
How does classic infantile Pompe disease present?
Rapidly progressive entity manifesting in early infancy with hypotonia, HCM and respiratory distress
What is essential for survival beyond infancy in classic infantile Pompe disease?
Prompt diagnosis and initiation of enzyme replacement therapy with recombinant human acid alpha glucosidase
True or False: Late-onset Pompe disease isn’t typically associated with cardiac manifestations?
True
What is normal velocity flow in the ductus arteriosus on a fetal echocardiogram?
0.6-1.4m/sec
What is the size of the ductus arteriosus equivalent to in fetal life?
Pulmonary trunk and descending aorta
True or False: In fetal life, the ductus arteriosus carries the majority of the fetal RV output into the descending aorta?
True
Depending on gestational age, what % of the RV output actually flows into the developing lungs?
10-25%
How is ductal patency maintained during fetal life?
Regulatory action of prostaglandins, nitric oxide, and low fetal O2 saturations
What causes premature ductal constriction in a fetus?
-Extrinsic agents: NSAIDS like indomethacin or herbal supplements
-Idiopathic
*Uncommon and often underrecognized, but can have bad consequences
What is the result of prenatal ductal constriction and ductal closure?
-Acute increase in fetal RV afterload
-Results in RVH, TR, RAE and increase R-L shunting across the foramen (depends on severity of ductal constriction)
-Increased pressure in pulmoanry vessels can cause dilation of MPA and branches with PS, PI or pulmonary vascular disease (thickening of media of pulmonary arterioles in response to obligatory increased flow to lung parenchyma)
-Severe cases- progressive RV failure resulting in hydrops fetalis and fetal demise
What is the most common echo finding in premature ductal constriction?
Disproportionate RVH
What are some findings on fetal echo in premature ductal constriction?
-Disproportionate RVH (most common)
-Ductus arteriosus narrow (much smaller than adjacent pulmonary trunk)
-Color Doppler with high-velocity jet across ductus arteriosus into descending aorta
-PI <1.9
-RV dilation
-TR
-Right heart failure
What is the pulsatility index?
-Measure of resistance to flow
-Peak systolic velocity-End diastolic velocity/Mean velocity
What is the normal range of pulsatility index for the ductus arteriosus?
1.9-2.5
In the presence of ductal constriction, what is the pulsatility index?
<1.9
What findings on fetal echo predict imminent fetal hydrops?
-Prominent reversal in ductus venosus flow with atrial contraction
-Presence of umbilical venous pulsations
What should be done if ductal constriction is seen on fetal echo?
-Close serial follow-up
-Maternal history to assess for possible causes (NDAIDS, etc) and discontinue is able
-Consider delivery with worsening RV function and impending hydrops (after birth PVR drops and decreases RV afterload)
What do the postnatal manifestations and overall outcome of ductal constriction in utero depend on?
Severity, duration and gestational age at onset
True or False: Ductal constriction is rare prior to 27 weeks gestation and the risk increases with advancing gestational age?
True
What are postnatal symptoms of ductal constriction?
-Mild cyanosis
-PPHN
-Severe respiratory distress
-Neonatal death
What may be needed postnatally for an infant with ductal construction?
-Close monitoring
-O2
-Pulmonary vasodilators
-Ventilator support
-ECMO
True or False: In some instances, fetal ductal closure is diagnosed postnatally in a cyanotic neonate with disproportionately thickened RV, R-L shunt at atrial level and absent ductus arteriosus within 24 hours of birth?
True
What is the result of premature constriction and closure of the fetal ductus arteriosus?
Acute increase in the RV afterload in the fetus
*Severe cases, progressive RV failure resulting in hydrops and fetal demise
What are the key echo findings in premature ductal cosntriction?
Disproportionate RVH, narrow ductus arteriosus with accelerated flow, ductal PI of <1.9
What can occur postnatally due to premature ductal construction?
-Mild cyanosis
-PPHN
-Severe respiratory distress
-Neonatal death
*Depends on the degree, duration and developmental stage at onset of ductal constriction
What are the major Jones criteria for acute rheumatic fever in the low-risk population?
-Carditis: Clinical or subclinical
-Polyarthritis
-Syndenham chorea
-Erythema marginatum
-Subcutaneous nodules
What are the minor Jones criteria for acute rheumatic fever in the low-risk population?
-Polyarthralgia
-Fever (>38.5C)
-ESR >60 and/or CRP >3
-Prolonged PR interval (unless carditis is a major criterion)
What is required to diagnose acute rheumatic fever?
2 major
1 major + 2 minor
Evidence of preceding strep infection
Rheumatic carditis is seen in what % of acute rheumatic fever cases?
40-70%
Where is the inflammation in rheumatic carditis?
All layers of the heart (pancarditis)
What is the predominant feature in rheumatic carditis?
Valvulitis
What is the most common cardiac manifestation of acute rheumatic carditis?
-MR (occurs in 95% of cases)
-Then AI (20% with MR and 5% isolated AI)
What is the clinical presentation of rheumatic carditis?
Ranges from asymptomatic murmur to acute severe heart failure
What is often an early sign of carditis?
Tachycardia
Describe the murmur of MR that can be seen in carditis due to acute rheumatic fever?
-High-pitched
-Holosystolic
-Cardiac apex with radiation to the axilla
-Often soft (even if significant regurgitation)
-May hear a middiastolic rumbling murmur of relative MS (Carey-Coombs murmur)… but isolated MS doesn’t occur in acute rheumatic carditis
True or False: In carditis due to acute rheumatic fever, mild MR often resolves whereas moderate to severe MR often progresses to chronic rheumatic heart disease?
True
What is the most common valvular lesion in adults with chronic rheumatic heart disease?
Mitral stenosis
*Can initially have MR that improves with subsequent development of MS many years later
*AS is another late sequelae of rheumatic fever, occurring 20-30 years after the acute episode
Describe the murmur heard with isolated AI
-Soft
-Early diastolic
-Decrescendo
*Isolated AI can occur with acute rheumatic carditis, but isn’t the most common manifestation
How is rheumatic carditis classified?
Pancarditis, but is predominantly a valvulitis
What is the most common valvular abnormality in acute rheumatic fever?
MR
What is the natural history with mild MR in acute rheumatic fever?
Often resolves
What is the natural history with moderate-severe MR in rheumatic heart disease?
Often progresses to chronic rheumatic heart disease
Describe what happens in a double chambered RV?
-Perimembranous VSD and development of obstructive RV muscle bundles
-Leads to a higher-pressure RV proximal to the RV muscle bundles and a lower-pressure RV distal to the RV muscle bundles
-Proximal portion of RV has a high RV pressure (and high TR jet gradient and low VSD gradient)
-There will be a high gradient across the RV muscle bundle
-PV is usually normal and there will be no significant additional gradient across the pulmonary valve
-PA pressure is normal
When does double-chambered RV usually present?
-Infancy or childhood
-Can be diagnosed in adults
Double-chambered RV is frequently associated with what other form of congenital heart disease?
Perimembranous VSD (90% of cases)
*VSD may not be seen in a patient with isolated double chambered RV, but there may have been a VSD that closed spontaneously
What is often seen in association with a VSD and double-chambered RV?
Subaortic membrane
What other forms of CHD is double chambered RV associated with?
-Perimembranous VSD
-Subaortic membrane
-ToF
-Ebstein
-DORV
-Single ventricle variants
-Other forms of CHD
Describe the development of double chambered RV from a pathological perspective
-Progressive hypertrophy of anomalous RV muscle located below (proximal to) the infundibular septum
-Includes hypertrophy of the crista supraventricularis, trabecular tissue, or moderator band
What causes double chambered RV?
-Abnormal blood flow patterns within RV may lead to abnormal RV muscular hypertrophy
-Often develops as a perimembranous VSD decreases in size- possibly due to higher flow gradient across the VSD entering the RV body and anomalous RV muscle bundles
-Also may be that VSD becomes smaller or closes spontaneously as adjacent anomalous RV muscle bundles hypertrophy with increasing gradient/obstruction from the double chambered RV
-Can also develop in patients who have undergone surgery for VSD closure
What do the symptoms associated with double chambered RV depend upon?
Degree of obstruction and presence of associated congenital heart abnormalities
What are some of the possible symptoms associated with double chambered RV?
-Exercise intolerance
-Dyspnea
-Syncope
-Chest pain
-Arrhythmias
-Combination
*Most children are asymptomatic
What has been reported in patients with unrepaired double chambered RV that can lead to acute symptoms caused by a sudden increase in the obstruction?
Endocarditis
What are some of the physical exam findings seen in double chambered RV?
-SEM without a valve click (differentiates from RV obstruction from valvar PS)
-RV heave or thrill (if moderate to high gradient and if RV proximal to level of obstruction is significantly hypertrophied)
What is seen on ECG in double chambered RV?
RV hypertrophy
How is double chambered RV diagnosed?
-Children: Echo is usually sufficient (subcoastal or parasternal RV inflow-outflow imaging
-Adults: May need TEE, CT, MRI, cath or combination
What is done for surgical repair of double chambered RV?
-Resection of abnormal RV muscle, usually through the TV
-Presence of any associated cardiac abnormalities (VSD, etc. should be evaluated and addressed at the same time)
When is surgical repair of double chambered RV indicated?
-Peak pressure >40mmHg within RV body
-Increasing gradient
-Evidence of cardiac-related symptoms
True or False: Surgical repair of uncomplicated double chambered RV is highly successful with low morbidity and morality?
True- Reoperation for recurrent double chambered RV is unusual when there has been adequate surgical relief of RV obstruction
True or False: Transcatheter intervention via balloon angioplasty or stent placement is not usually successful as definitive repair of double chambered RV, but it has been performed in patients who are at high surgical risk?
True
Double chambered RV is most commonly seen in what patients?
Young patients in association with a restrictive perimembrnaous VSD
True or False: Most children with double chambered RV are asymptomatic?
True
When is surgical repair via resection of abnormal RV muscle bundles indicated for double chambered RV?
-Gradient greater than 40mmHg across the anomalous RV muscle bundles
-Presence of symptoms
-Associated anomalies that warrant surgical intervention
What is important as part of screening for adults with repaired CoA?
3D imaging
How often should an adult with repaired CoA have 3D imaging?
Every 5 years or less (depending on complexity of case)
Besides re-coarctation, what is a risk in patients who have undergone repair of coarctation?
Aneurysm at site of prior repair
Which patients with repaired CoA and are at increased risk for aneurysm at site fo repair?
Those who have undergone a polyethylene terephthalate (Dacron) graft repair
What is often required to diagnose an aneurysm in an adult with repaired CoA?
3D imaging via CT or MRI (echo can often miss large aneurysms)
Besides screening for aneurysm at the site of a CoA repair, what else is CTA or MRI helpful for in these patients?
Assessment of the size of the ascending aorta (especially if the patient has a bicuspid aortic valve)
Current guidelines suggest surgical intervention for aneurysm of the ascending aorta once it is above what measurement?
> 5-5.5cm
What surgical approach is an option for patients who have a large ascending aortic aneurysm, but a well- functioning aortic valve (even if bicuspid)?
Valve-sparing aortic root replacement
What is a big problem for patients who have undergone CoA repair (especially in those whose repair happens outside of infancy?
HTN
Persistent HTN may predispose someone with repaired CoA to what?
Early atherosclerotic heart disease
*Need to try to achieve goal directed medical therapy
All adults with repaired CoA should undergo what to evaluate for aneurysm or re-coarctation at least every 5 years?
3D imaging of aorta
What are options for 3D imaging of the aorta?
CT or MRI- Echo is helpful as a screening tool, but isn’t good to detect things like aneurysm (especially in repaired CoA patients)
What is a common problem in patients who have undergone repair of CoA?
HTN- Treatment needs to be aimed at goal-directed medical therapy
True or False: Routine stress tests are part of the follow-up assessment of patients who have CoA?
False
What is in the differential diagnosis for new-onset LV dilation and systolic dysfunction in a teenager?
-CHD
-Cardiomyopathy
-Myocarditis
-Athletes heart
What should be assessed during history for a teenager with new-onset LV dilation and systolic dysfunction?
-Recent viral illness (myocarditis)
-Palpitations (tachyarrhythmia-induced cardiomyopathy)
-Chest pain or syncope with exertion (coronary anomaly)
-Exercise intolerance
-Family history: Inherited forms of cardiomyopathy (dilated, arrhythmogenic, hypertrophic, LVNC) or CHD
In pediatrics, athlete’s heart is most often encountered in patients with what?
LVH and a questionable diagnosis of HCM
True or False; Athlete’s heart can overlap with other cardiomyopathies (DCM, arrhythmogenic cardiomyopathy, myocarditis)?
True
True or False: Exercise-induced cardiac remodeling manifests differently in athletes in endurance v. strength training?
True
Describe the exercise-induced cardiac remodeling seen in endurance athletes
-Volume overload during sustained high cardiac output
-Biventricular dilation
-Biatrial enlargement
-Low normal resting EF
-Mild-moderate eccentric LVH
What causes the eccentric hypertrophy seen in endurance athletes?
New sarcomeres are added in series to existing sarcomeres leading to volume overload-induced cardiac hypertrophy
*Distinct from pathologic hypertrophy in hypertrophic cardiomyopathy
True or False: There are dilation volume cutoffs for the LV and RV which reliably differentiate between physiologic v. pathologic heart dilation?
False- Unless the heart is markedly dilated
True or False: As little as 3-5 hours of exercise per week and >5 hours of exercise are associated with a high proportion of adults outside published normal ranges for both hypertrophy and dilation?
True
True or False: In athletes, EFs are often lower than one would expect at rest given dilation of the LV?
True
What is one way to distinguish a low-normal EF as being due to athletic status v. pathology?
Exercise test
-Athletes wouldn’t have exercise intolerance would probably have supranormal results on exercise testing without inducible arrhythmia
-Imaging at rest would show normal diastolic parameters
-Exercise imaging can show normalization of cardiac function
Athlete’s heart is a diagnosis of…
Exclusion (due to heightened awareness of SCD in young athletes)
*Need to consider athlete’s heart when factoring in exercise restriction… athletes with no pathologic disease can affect quality of life and economic opportunities
What can be done to distinguish between athletes heart and cardiomyopathy?
-Period of deconditioning (3-6 months) to see if parameters normalize
-If they don’t, findings are consistent with cardiomyopathy v. athlete’s heart
What are some forms of CHD that may be associated with ventricular dilation and decreased function over time?
-L-R shunt lesions (ASD, VSD, PDA, AVM)
-L obstructive lesions (CoA)
-LV volume overload (valvulopathy)
-Coronary anomalies
*These will often have associated PE findings except coronary anomalies
*Most picked up by echo, may need MRI or CT for something like sinus venosus ASD, coronary anomalies, aortic arch issues, etc
True or False: Findings of athlete’s heart can overlap with the various cardiomyopathies?
True- Dilated, hypertrophic, ARVC, myocarditis
Which form of heterotaxy has associated twin AV nodes and SVT
Right atrial isomerism
Which form of heterotaxy has associated complete heart block and bradyarrhythmias?
Left atrial isomterism
True or False: All patients with heterotaxy syndrome are at risk for both tachy and bradyarrhythmias?
True
What is the differential diagnosis when there is a change in QRS morphology on ECG?
-Intermittent preexcitation
-Aberrant conduction
-Ventricular rhythm
-Twin AV nodes
What is suggested when there is a change in QRS morphology always preceded by a change in the P-wave morphology?
Twin AV nodes
*When the atrial impulse occurs from one site, it conducts down the close AV node
*When the atrial stimulus occurs from a different site closer to the other AV node, conduction changes to that second AV node
What are clues that change in QRS morphology is due to intermittent preexcitation?
-Usually no change in P-wave morphology that precedes each change in QRS morphology
-Beats that are preexcited would have the characteristics of preexcitation (short PR, wide QRS, delta wave)
What can occur with premature atrial beats that come at a time when one of the bundles is refractory?
Aberrant conduction
What is rate-related aberrancy?
As the HR increases one of the bundles is refractory and not able to conduct
What situations can result in aberrancy?
Acidosis
Electrolyte abnormalities
*QRS complex would gradually change not be a beat to beat difference
True or False: There is usually not a change in P-wave morphology with aberrant conduction?
True
What is the differential diagnosis for a change in QRS morphology?
-Intermittent preexcitation
-Aberrant conduction
-Ventricular rhythm
-Twin AV nodes
What is the differential diagnosis of a wide QRS tachycardia?
-Ventricular rhythm (v-tach, torsades)
-Supraventricular rhythm with aberrancy (sinus tachycardia with underlying BBB or pre-excitation, SVT with aberrancy)
-Antidromic supraventricular tachycardia
-Artifact
How can you distinguish sinus rhythm with artifact?
-See if QRS complexes can be detected within the artifact recording… will see narrow QRS complexes marching through the time of the artifact at a rate similar to what was seen before/after artifact
-Can also look at other leads as well
What is considered a toxic digoxin level?
> 2ng/mL
Generalized ST segment depression, T-wave inversion, accelerated junctional rhythm with atrioventricular block, curved sagging of ST segments?
Digoxin overdose
True or False: Digoxin toxicity can cause nearly every possible arrhythmia?
True
What are some arrhythmias that are more suggestive of digoxin toxicity?
-New-onset AV block
-Accelerated junctional rhythm with or without high-degree AV block
-Nonparoxysmal atrial tachycardia with AV block
-Bidirectional ventricular tachycardia
What will happen if digoxin toxicity is not promptly recognized and treated?
-Ventricular fibrillation
-May not be responsive to defibrillation
What is lifesaving in cases of digoxin toxicity?
Digoxin-specific antibody fragements
What can be given for ventricular tachyarrhythmias due to digoxin toxicity?
Lidocaine or phenytoin (while awaiting digoxin antibodies)
What can be given for bradyarrhythmias due to digoxin toxicity?
Atropine (while awaiting digoxin antibodies)
What are common symptoms seen in digoxin toxicity?
GI- Diarrhea and vomiting
What lab abnormality is seen in digoxin toxicity?
Hyperkalemia (indicative of severe digoxin toxicity)
How does digoxin toxicity cause hyperkalemia?
-Blocks the sodium and potassium adenosine triphosphatase pump
-Results in increased extracellular potassium that causes hyperkalemia
What lab derangement can occur once antidigoxin antibodies are given for digoxin toxicity?
Hypokalemia- requires prompt correction
Coadministration of what results in an increase in serum digoxin levels?
Amiodarone
How is digoxin excreted?
Via kidneys through glomerular filtration and active tubular secretion
Why does amiodarone result in increased serum digoxin levels?
It likely inhibits renal tubular secretion of digoxin
What needs to be done to the digoxin dose in patients who are concomitantly using amiodarone?
Lower by 50%
*Need to monitor digoxin levels carefully
What can happen if amiodarone is started without lowering digoxin dose?
Digoxin toxicity
An increase in what lab value may result in increased digoxin levels?
Creatinine- Digoxin is excreted by the kidneys, reduced kidney function could increase levels
The ingestion of what dose of digoxin by a child without underlying heart disease can result in serious toxic effects?
0.3mg/kg
True or False: Measurement of serum digoxin concentrations in kids doesn’t always correlate with toxic effects?
True- Need a high index of suspicion and familiarity with the clinical signs and ECG changes
True or False: Once antidigoxin antibodies are administered, serum digoxin levels can’t be relied on and a 2nd dose may be needed after 12 hours based solely on clinical findings?
True
When should extracorporeal cardiopulmonary resuscitation be considered?
In refractory cardiac arrest for select populations (children with heart disease) with a witnessed in-hospital cardiac arrest in settings with adequate systems and resources to use ECPR effectively
True or False: On the basis of current studies, there is insufficient evidence to recommend consideration of extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest?
True
*Indications rapidly evolving and individual patients considerations should be discussed with the responsible ICU, ECMO and surgical teams before determining any specific patient’s eligibility
Can patients in the ICU for noncardiac conditions with witnessed arrest be considered for extracorporeal cardiopulmonary resuscitation?
Yes… but patients with things like septic shock are unlikely to receive adequate flow/supports through peripheral cannulation and would have less favorable outcomes (unless surgeon would do central cannulation)
What does extracorporeal cardiopulmonary resuscitation involve?
Adjunctive use of mechanical cardiopulmonary support to assist during or immediately after cardiopulmonary resuscitation
When should extracorporeal cardiopulmonary resuscitation be considered?
In refractory cardiac arrest for select populations (children with heart disease) with a witnessed in-hospital cardiac arrest in settings with adequate systems and resources to use ECPR effecitvely
What are commonly used benzodiazepines in pediatric cardiac patients?
-Lorazepam
-Diazepam
-Midazolam
How do benzodiazepines work?
Bind to the GABA (y-aminobutyric acid) A receptors, mostly in the CNS, and hyperpolarizing them to be more responsive to GABA inhibition
-Leads to sedation, anxiolysis and decreased excitability
What are the effects of benzodiazepines?
Sedation, anxiolysis, decreased excitability
What causes the cardiac effects of benzodiazepiens?
Combination of reduced sympathetic activity caused by sedation and reduced parasympathetic stimulation in response to GABA activation in the nucleus ambiguus and reduced vagal tone
What are the cardiac effects of benzodiazepines?
-Depends on dose
-Hypotension
-Bradycardia or tachycardia: Attributable to reduction in sympathetic stimulation or overinhibition of parasympathetic outflow and baroreceptor reflex stimulation by lowered BP
-Direct negative inotropic effect on myocardial contractility (due to Ca channel suppression in the SR)
True or False: Benzodiazepines are generally well tolerated at low doses?
True
True or False: Benzodiazepines have been directly implicated in acute CV collapse and cardiac arrest (mostly at high doses), in rapid IV bolus, or in neonates/patients with cyanotic CHD?
True- Use with caution
What is a benzodiazepine antagonist?
Flumazenil
How does flumazenil work?
Competitive inhibition at the benzodiazepine-binding site on GABA receptors
*Used as an antidote in benzodiazepine overdose
What causes the cardiac effects of flumazenil?
Increased sympathetic stimulation with benzodiazepine reversal
What are the cardiac effects of flumazenil?
-Tachycardia
-Ventricular ectopy
-SVT
*Older adults, can see complete heart block and spontaneous cardiac arrest, but not understood why this happens
What happens to patients that receive flumazenil?
-Transient increase in circulating epinephrine and norepinephrine
-Results in increased HR, BP, PA pressure, wedge pressure and LVEF
-No significant increase in CVP
What are the non-cardiac effects of flumazenil?
-Seizures or status epilepticus (can be fatal)
-Anxiety
-Agitation
Which patients have the most concerning side effects from flumazenil?
Those with longstanding benzodiazepine dependence (seizures and status epilepticus which can be fatal)
What can happen if a patient has had a large dose of benzodiazepine and was then given flumazenil?
Can develop rebound sedation after antagonistic effects of flumazenil wear off
What causes benzodiazepines effects on cardiac activity?
-Reduced parasympathetic outflow (reducing vagal tone)
-Reduced sympathetic stimulation
-Direct myocardial suppression
What are benzodiazepine antagonist effects on cardiac activity attributable to?
Increased sympathetic outflow causing a transient increase in circulating epinephrine and norepinephrine levels
True or False: Benzodiazepines and their antagonists must be used with extreme caution in patients with cyanotic CHD, neonates and those with abnormal cardiac function?
True
Grade 2/6 systolic murmur along the left sternal border that becomes louder when rising from a crouched position?
LVOT murmur (think HOCM)
What are some ECG findings consistent with HOCM?
-Sinus bradycardia
-Pronounced ventricular hypertrophy by voltage
-T-waves in precordial leads with a strain pattern
What is the Sokolow-Lyon criteria for ventricular hypertrophy?
Sum of the R wave in V6 and S wave in V1 >35mm
True or False: LVH on resting ECG has a low sensitivity/specificity and PPV for LVH?
True
What should you consider for an ECG with deep S wave in V6, tall R wave in V1 and t-wave inversion in the lateral leads?
-Pulmonary HTN
-PS
-Other pathologies involving RV and outflow tract
What is the modified Bernoulli equation?
Pressure Gradient (mmHg) = 4V2 (V = peak velocity)
In the modified Bernoulli equation, what is ingored?
The proximal velocity- ignored if it is <1 M/sec
*When a fixed or dynamic proximal gradient is present, the accelerated velocity must be factored into the equation
True or False: In the setting of severe multilevel obstruction, the presence of 2 stenoses in series may make it impossible to ascertain the precise individual contribution of each by echo?
True
Which tends to be higher, Doppler peak gradients or peak-to-peak cath gradients?
Doppler peak gradients
What constitutes mild pulmonary valve stenosis?
Peak velocity <3M/sec
Peak gradient <36mmHg
What constitutes moderate pulmonary valve stenosis?
Peak velocity 3-4M/sec
Peak gradient 36-64mmHg
What constitutes severe pulmonary valve stenosis?
Peak velocity >4M/sec
Peak gradient >64mmhg
An RV pressure of what % systemic is consistent with moderate pulmonary stenosis?
50-75%
True or False: Severity of PS using Doppler derived gradients has demonstrated a reasonable correlation between peak-to-peak gradients obtained by catheterization?
True
How can you calculate pressure decrease across a stenotic semilunar valve by echo?
Peak velocities obtained from CW Doppler signals across a stenotic semilunar valve are converted into a pressure gradient by the modified Bernoulli equation
What are other names for a doubly committed juxta-arterial VSD?
-Subpulmonary
-Supracristal
-Subarterial
Where is a double committed juxta-arterial VSD seen on a short axis view on echo?
-Proximal to the pulmonary valve and more distal from the tricuspid valve
*Perimembranous VSD are seen in close proximity to the tricuspid valve
What can be used to estimate the pressure gradient between the right and left ventricles in patients with VSDs?
CW Doppler
How do you estimate the pressure gradient between the RV and LV in a patient with a VSD?
*Doppler measurement of peak velocity across defect
*Convert to pressure gradient using modified Bernoulli equation (P = 4V2
*Subtract pressure gradient from patient’s SBP to estimate RVSP and PA pressure
True or False: In the absence of RVOTO, smaller VSDs are nearly always associated with restrictive hemodynamics?
True- High velocity and high peak trans-septal gradient with low estimated RV pressures
What type of VSDs tend to demonstrate unrestrictive hemodynamics?
Large VSD
*Low velocity and low peak trans-septal gradient with elevated estimated RV pressures
What causes a doubly committed juxta-arterial VSD?
Absence of the subpulmonary infundibulum (this normally serves to lift the pulmonary trunk away from the base of the heart)
*Results in fibrous continuity between the aortic and pulmonary valves
What can happen to the aortic valve in a doubly committed juxta-arterial VSD?
Risk for aortic valve leaflet prolapse (most commonly the right coronary cusp) due to deficiency of muscular support
What should be done for a small, restrictive, doubly committed juxta-arterial VSD?
-Supportive care
-Routine follow-up to assess for future evidence of aortic valve prolapse or AI
What information does Spectral Doppler provide about VSD hemodynamics?
Characterizes restrictive v. nonrestrictive based on the peak velocity by using the modified Bernoulli equation to estimate peak trans-septal pressure gradients
Why do doubly committed juxta-arterial VSDs need to be monitored so closely?
Risk for AV prolapse
What defines critical PS?
Ductal dependence to maintain adequate pulmonary blood flow
What is the treatment of choice for valvar PS?
Pulmonary balloon valvuloplasty
What might be needed following pulmonary balloon valvuloplasty?
PGE
Why might an infant need PGE following pulmonary balloon valvuloplasty?
RVH associated with poor compliance and a hyperdynamic infundibulum can result in preferential R-L atrial shunting of systemic venous return and a reduced RV output
What can be given after pulmonary balloon valvuloplasty to improve diastolic filling of the noncompliant, hypertrophied and potentially hypercontractile RV?
Beta blockade
How does beta blockade help after pulmonary balloon valvuloplasty?
-Reduces HR
-Reduces contractility
-Improves diastolic filling
*This can promote antegrade flow across the pulmonary valve
What kind of receptors are beta-adrenergic receptors and where are they located?
-Transmembrane guanine nucleotide (G) protein-coupled receptors
-Located on the cardiac sarcolemma
What activates B-adrenergic receptors?
-Norepinephrine
-Epinephrine
-Catecholamines
Stimulatory (Gs) proteins link G-protein coupled receptors to what, which then produces what?
-Adenylyl cyclase
-Cyclic adenosine monophosphate (cAMP) from adenosine triphosphate
How do inhibitory (Gi) protein receptors inhibit the production of cAMP?
Deactivate adenylyl cyclase
What does cAMP activate that results in an increase in the rate/force of myocardial contraction through the opening of Ca channels and increase in myocardial relaxation through increased reuptake of Ca?
Protein kinase A pathway
How does Gs protein receptor stimulation affect conduction?
-Accelerates rate of conduction
-Gs protein receptor stimulation within the conduction system increases the pacemaker current within the sinus node… accelerates rate of conduction
What interrupts the link between G-protein coupled receptors and adenylyl cyclase resulting in decreased contractility and HR?
Muscarinic stimulation of Gi protein receptors after vagal activation
What improves with a reduction in HR?
Filling time- there is an increase in the amount fo time spent in diastole during the cardiac cycle
Where are B1 adrenergic receptors found?
Heart
Where are B2 adrenergic receptors found?
Bronchial and vascular smooth muscle
What do B-blockers result in?
-Reduction in rate/force of myocardial contraction
-Reduction in pacemaker current and rate of conduction
What is the difference between first, second and thirs generation B-blockers?
-First generation are nonselective for B1/B2 blockade
-Second generation have a relative selectivity for B1
-Third are nonselective with additional benefits like alpha-blocking activity
Propranolol and nadolol are what generation B-blocker?
1st
Metoprolol, atenolol and esmolol are what generation B-blocker?
2nd
Carvedilol is what generation B-blocker?
3rd
What are 2 proposed mechanisms for Beta-blockers decreasing BP?
-Reduced CO
-Blockade of B-receptors within the renal juxtaglomerular complex (reduces circulation levels of renin)
What causes the reduction in myocardial O2 demand for patients taking a B-blocker?
-Reduction in HR and BP
-Limiting increases in contractility that result from exercise or agitation
What are the effects of B-blockers on the heart?
-Reduction in rate and force of myocardial contraction
-Reduction in pacemaker current and rate of conduction
Elevated partial pressure of PCO2 with proportionately low pH?
Acute respiratory acidosis without compensation
In acute onset respiratory acidosis, the pH decreases by 0.08 for every _mmHg increase in PCO2 above normal (40mmHg)?
10
In the case of chronic respiratory acidosis (>72 hours), metabolic compensation with an increase in serum bicarbonate is predicted by what formula?
3.5 * (change in PCO2/10)
What type of ventilation is optimal for Glenn circulation and why?
-Negative pressure
-Extubated
-Spontaneous breathing
-SVC blood return to the pulmonary vasculature is passive
What are the effects of mild hypercapnia (PCO2 45-55mmHg) on Glenn physiology?
-Leads to cerebral vasodilation
-Leads to increased cerebral blood flow
-May improve perfusion through the Glenn circulation
Giving what can improve metabolic acidosis or a pulmonary HTN crisis?
NaBicarb
If a patient doesn’t have adequate ventilatory capacity, giving what can worsen hypercapnia and acidosis, potentially leading to pulmonary vasoconstriction?
Bicarb
What should be done to the ventilator settings if the lungs are overinflated or there is inadequate exhalation (like in bronchospasm)?
Decrease PEEP
Worsening compliance can lead to what metabolic derangement?
Respiratory acidosis
What should always be considered in cases of respiratory acidosis?
Malpositioned ET tube
Permissive hypercapnia up to what improves pulmonary blood flow in the Glenn circulation?
55mmHg
*But hypercapnia leading to acidosis may also trigger pulmonary vasoconstriction
What defines tricuspid atresia?
-Cyanotic CHD
-Complete absence of tricuspid valve, obligate R-L atrial level shunting, hypoplasia of RV
What do the clinical features in tricuspid valve atresia largely depend on?
-Great artery relationship
-Presence or absence of obstruction to pulmonary blood flow or systemic flow
True or False: Most patients with tricuspid atresia have normally related great arteries?
True
What % of patients with tricuspid atresia have D-TGA?
12-25%
*Aorta comes from hypoplastic RV
In tricuspid atresia, what does a large VSD in the setting of normally related great arteries result in?
Overcirculation
In tricuspid atresia, what does a restrictive VSD, pulmonary stenosis or pulmonary atresia result in?
Reduced pulmonary flow and ductal dependency
Tricuspid atresia with D-TGA and restrictive VSD result in what?
Compromised systemic blood flow- may be associated with a hypoplastic aortic arch or CoA
True or False: All patients with tricuspid atresia are committed to the single ventricle pathway?
True
-Goal to transition from parallel systemic and pulmonary circulations to circulations that are in series
What will happen to a baby with time who has tricuspid atresia with normally related great vessels, a large VSD and no evidence of obstruction to pulmonary blood flow?
Will develop excessive pulmonary blood flow as PVR drops- may be tachypneic, etc
What should be done for an infant with tricuspid atresia with normally related great vessels, a large VSD and no evidence of obstruction to pulmonary blood flow?
-Begin diuretic therapy
-Consider MPA band to protect pulmonary vascular bed from excessive pulmonary blood flow/high pressure (this makes sure the patient will be a candidate for the bidirectional Glenn then Fontan)
Why do patients need to be monitored for cyanosis after PA band in the setting of tricuspid atresia with normally related great vessels?
-Ventricular hypertrophy can develop
-This can lead to restriction of the ventricular level shunt
What needs to be done for an infant with tricuspid atresia, normally related great arteries and reduced pulmonary blood flow due to a restrictive VSD, PS or PA?
-Need a L-R shunt
-PGE to maintain ductal patency
-Eventual systemic to PA shunt or ductal stent for stable source of pulmonary blood flow
A DKS (MPA to ascending aorta) with systemic to PA shunt is needed in tricuspid atresia with what?
D-TGA and restrictive VSD
-Will have restricted systemic blood flow from subaortic obstruction from VSD and pulmonary overcirculation from increased CO from LV to MPA
-May need ductal patency to ensure adequate systemic output until surgery
Patients with tricuspid atresia and what will experience pulmonary overcirculation and will benefit from PA banding?
-Normally related great vessels
-Large VSD
What type of tricuspid atresia patients are ductal dependent pending establishment of a stable source of pulmonary blood flow?
-Normally related great arteries
-Reduced pulmonary blood flow due to restrictive VSD, PS, or PA
What type of tricuspid atresia patient will have restrictive systemic blood flow and pulmonary overcirculation?
-D-TGA
-Restrictive VSD
What is needed for tricuspid atresia patients with D-TGA and restrictive VSD?
-DKS with systemic to PA shunt (ensures adequate systemic blood flow with reduced low pressure pulmonary flow)
*Hypoplastic arch or CoA can also be addressed
When does subaortic stenosis most often occur?
In association with other forms of CHD or after prior surgical repair of CHD (rare as an isolated defect)
What are the most common congenital cardiac anomalies associated with subaortic stenosis?
-VSD
-PDA
-Bicuspid aortic valve
-CoA
-IAA (especially with co-existing Shone syndrome
-AVCD
What can be seen years following repair of a posterior malalinged VSD and IAA?
LVOTO due to subaortic membrane
What is IAA usually associated with?
-Posterior malalignment of the infundibular ventricular septum with a VSD in that region
-Aortic valve hypoplasia (bicuspid)
-AS (can be significant)
What does neonatal repair of IAA typically include?
-VSD patch closure
-Aortic arch reconstruction
What are options for neonatal repair of IAA + VSD in patients where primary VSD closure may not address the LVOTO (or LVOT stenosis or AS are significant)?
-Resection of infundibular septum with VSD enlargement
-Single or staged repair via Norwood-Rastelli approach (depending on degree of LVOT narrowing and AV morphology)
-Single ventricle palliation (severe LVOTO)
True or False: Patients with interrupted aortic arch/VSD often have residual and/or recurrent LVOTO?
True- may need to be re-addressed surgically
True or False: It would be unusual for a neonate to require isolated AV canal repair?
True (usually done at a few months of age)
True or False: Subaortic membrane is not a common post-operative complication after TAPVR?
True
What is a common complication after IAA/VSD repair?
Subaortic stenosis
What infants are considered high-risk and should be referred to a neurodevelopmental follow-up program?
-Exposure to postnatal corticosteroids
-TPN use
-In utero alcohol, nicotine or controlled substances
-High-risk cyanotic lesions
-Prolonged critical illness
-Neonatal surgery with CPB
-Prematurity
-Developmental delay
-Suspected syndrome or genetic anomaly
-Mechanical circulatory support
-Transplant
-Cardiopulmonary resuscitation
-Seizures
-Abnormal neuroimaging
*Does not specifically list high-risk medications
What are the most commonly implicated neonatal medication exposures associated with neurodevelopmental disorders?
-Neuro-sedative agents
-Antiepileptics
-Glucocorticoids
What are some of the adverse effects of loop diuretics (furosemide and bumetanide)?
-Hypokalemia
-Hypochloremia
-Metabolic alkalosis
-Hypercalciuria (leads to bone loss/renal calcification with chronic use)
-Ototoxicity
What is the ototoxic effect of loop diuretics thought to be related to?
-Peak serum concentration reaching a toxic level
*Recent study reported complete elimination of sensorineural hearing loss in patients with single ventricle disease after QI slowing the infusion rate of IV loop diuretics (lower peak serum concentration at slower rates)
True or False: Bumetanide has significantly less ototoxicity than furosemide at equivalent diuretic doses?
True- even though it has a similar MOA on the cochlea
True or False: The ototoxic effects of loop diuretics may be delayed?
True
Why is it important for patients who have required loop diuretics to have good neurodevelopmental follow-up?
-Risk for ototoxicity and sensorineural hearing loss
-Ototoxic effects may be delayed
-Many patients discharged home on diuretics
-Need comprehensive neurodevelopmental follow-up including interval language development assessments
True or False: In-utero exposure to acetaminophen has been associated with autism and ADHD?
True
*But no data linking postnatal acetaminophen with neurodevelopmental disorders
True or False: No studies have independently associated prostaglandins or ranitidine with neurodevelopmental delays?
True
What patients should be referred to a comprehensive neurodevelopmental follow-up program?
-Complex CHD
-Risk factors for neurodevelopmental disorders: Exposures to antiepileptics, neurosedatives, high-dose loop diuretics, corticosteroids
What is the position of the MPA relative to the aorta in D-TGA?
Posterior and leftward to the aorta
A large LA, elevated E/A ratio and short MV deceleration time are all indicative of what?
Abnormal diastolic function
Chronic LA HTN due to restrictive physiology can result in what?
-Arrhythmias
-Pulmonary HTN
-Thromboembolic events (stasis or pooling of blood in atria
*Could all potentially result in a syncopal episode
What happens to patients with restrictive physiology during exercise?
-Increased HR can help increase CO up to a point
-These patients have a relatively fixed SV which decreases ability to compensate for increased demands of exercise (ventricles fill less well with elevated HR)
True or False: LAE in the absence of significant MR is a relatively good marker for diastolic dysfunction in children?
True
Describe the findings on mitral valve inflow Doppler that are consistent with restrictive physiology
-Tall, narrow mitral E wave
-Diminutive A wave
-E/A ratio >3
-E wave deceleration time short (<130ms)
What causes the short E-wave deceleration time on mitral inflow Doppler in restrictive physiology?
Rapid equalization of the LA filling pressure with the elevated LVEDP in a stiff, less compliant ventricle
True or False: No single echo parameter for diastolic function should be used in isolation as a determiner for the presence of diastolic dyusfunction?
True
True or False: The application of adult echo criteria for diastolic dysfunction has overall poor correlation in pediatric patients?
True
What are the more useful parameters in children for the assessment of diastolic dysfunction?
-LA volume/size
-Short mitral deceleration times
What gives the most accurate assessment of the ventricular filling pressures and quantification of diastolic abnormalities (including restrictive physiology)?
Direct measurement of LVEDP via cath
*Also gives PA pressures and PVR which can become significantly elevated with restrictive physiology
What are some of the risks associated with cardiac cath?
-Myocardial perforation
-Arrhythmia
-TV or vessel injury
What findings would you expect on cath for a patient with a tall, narrow mitral E wave, diminutive A wave, E/A ratio >3 and E wave deceleration time <130msec on echo?
Elevated LVEDP (restrictive physiology)
Despite preserved systolic function on echo, patients after aortic valve interventions are at risk for what?
Diastolic dysfunction (restrictive physiology being on severe end of spectrum)
True or False: All patients with CHD should be educated about their diagnosis and the reasons they will need lifelong cardiology care?
True
What are some of the life-long risks for patients with CoA who have undergone surgical or catheter-based repair?
-Recurrent CoA
-Aortic aneurysms
-Pseudoaneurysms
-Aortic dissection
-HTN
What % of patients with repaired CoA require reintervention in adulthood?
11%
What kind of imaging should all adults with repaired CoA have periodically?
3D imaging of the aorta via MRA or CTA
What are some of the Class I recommendations for adults with repaired CoA?
-3D imaging of aorta via MRA or CTA periodically
-Checking resting BP in upper/lower extremities to assess for recoarctation
-Surgical repair or catheter-based stenting in patients with recoarctation and HTN
-Goal-directed medical therapy for the management of HTN
When treating an adult s/p CoA repair for HTN, what do you have to be cautious about?
That degree of CoA isn’t so severe to acutely decrease LE perfusion with aggressive anti-hypertensives until recurrent CoA is managed appropriately
What are the Class II recommendations for adults with repaired CoA?
-Ambulatory BP monitoring to diagnose/manage HTN
-Screening for intracranial aneurysms
-Exercise testing to assess for exercise-induced HTN
-Balloon angioplasty in patients with CoA who are ineligible for stent placement or surgical repair
Intracranial aneurysms can occur in up to what % of patients with CoA?
10%- and can increase in frequency with age
True or False: In adults s/p CoA repair, TEE may be able to identify an area of recurrent CoA, but can’t profile the entire thoracic aorta and may be insufficient for identifying aneurysms, pseudoaneurysms, dissections or remotely located CoA?
True- why cross-sectional imaging is more appropriate (especially with incomplete history or gaps in follow-up)
What is the most common genetically inherited hyperlipidemia?
Familial hypercholesterolemia
Which is more common, heterozygous or homozygous familial hypercholesterolemia?
Heterozygous
-Heterozygous: 1/200-250
-Homozygous: 1/160,000-300,000
When should children be screened for hyperlipidemia regardless of risk factors or comorbidities?
9-11 and 17-21
Which children should have hyperlipidemia screening starting after age 2?
-CV Risk Factors: CHD, Kawasaki disease with persistent coronary artery aneurysms, heart transplants
-Non-CV Risk Factors: Chronic renal disease, DM, stem cell transplants
Familial hypercholesterolemia should be suspected in any pediatric patient with what findings?
-Fasting LDL >160mg/dL
-Family history of premature CAD or elevated LDL in a 1st degree relative
If an LDL level > what is detected in a patient <20 years, there is an 80% chance of familial hypercholesterolemia?
190
Mutations in what genes can be detected by genetic testing for familial hyperlipidemia?
-LDL receptor
-Apolipoprotein B
-Proprotein convertase subtilisin/kesin type 9 (PCSK9)
*Genetic testing isn’t routinely recommended
What are the first line of pharmacologic agents to treat familial hypercholesterolemia in children and adults?
Statins
How do statins work?
-Inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (rate-limiting enzyme in cholesterol biosynthesis)
-Upregulates LDL receptors in the liver
Besides lowering LDL, what other effects do statins have?
-Modest effect on lowering triglyceride levels
-Modest effect on raising high-density lipoprotein cholesterol levels
What does the expected effect on LDL lowering with statin use depend on?
Dose and intensity of the statin
What are considered to be the more potent statins?
-Atorvastatin
-Rosuvastatin
Which 2 statins are approved for use in children as young as 8?
-Pitavastatin
-Pravastatin
Which statins are approved for use in children over 10?
-Atorvastatin
-Rosuvastatin
-Lovastatin
-Fluvastatin
*In addition to pitavastatin and pravastatin
How are statins started/titrated in children?
-Start with lowest possible dose
-Gradual up-titration to achieve desired LDL <130
What are some of the adverse effects of statins?
-Statin-associated muscle symptoms
-Increase in hepatic transaminases
-Transient GI upset
-Concern for teratogenicity
True or False: Multiple studies have found no adverse effects of statins on growth, development or sexual maturation?
True
What are clinically significant adverse effects of statins that require discontinuation of therapy?
-Severe myopathy
-Rhabdomyolysis
-Hepatic dysfunction
*Rare in children and adolescents
How often should LFTs be checked when starting a statin?
-Before initiation
-Repeat measurements at 4, 8 and 12 weeks after initiation
An elevation in hepatic transaminases above what is concerning and should prompt discontinuation of statin therapy?
> 3x upper limit of normal
*Should evaluate for alternative causes for the increase as well
True or False: If you stop a statin for elevated transaminases, you can re-initiate treatment with a statin at a lower dose (or different statin) with close monitoring of transamianses once the levels have normalized?
True
Besides LFTs, what other lab value should be measures before initiating a statin?
Creatinine kinase (CK)
When do repeat CK levels need to be checked when starting a statin?
Only if the patient has muscle symptoms
A CK level above what should prompt temporary discontinuation of a statin?
CK >10x the upper limit of normal
*or clinically significant statin-associated muscle symptoms- be sure to assess for alternative etiologies (exercise, hypothyroidism, trauma)
True or False: You can try to reinitiate statin therapy after it was discontinued due to elevated CK/muscle symptoms?
True- once levels/symptoms have normalized… re-start in controlled fashion at a lower dose
What do you need to counsel female patients about who are taking a statin?
Teratogenic effects of the drug
What can be given to patients with clinically significant elevations in TG levels to prevent acute episodes of pancreatitis?
Fenofibrate or bezafibrate (minimal effect on LDL)
