Exam 2 Flashcards
What is the definition of preload and afterload? Given these drugs, vasodilators, diuretics, angiotensin inhibitors, inotropic agents, and RAAS inhibitors, what are their effects on preload and afterload?
Pre-load: The volume of blood in the ventricles at the end of diastole. It’s decreased by dilation of veins. If it’s decreased, myocardial perfusion will go up & O2 consumption will go down.
After-load: The force distributed on the ventricular wall when pumping blood to the body. It’s decreased by dilation of arteries. If it’s decreased, O2 consumption will go down.
- Vasodilators: Dilates veins, which lowers preload & congestive symptoms (ex. nitrates, hydralazine)
- Diuretics: decrease blood volume, which helps with HTN & preload (?) (ex. furosemide, bumetanide, torsemide)
- Angiotensin inhibitors: Decrease pressure and volume, which helps with afterload & preload (?)
- Inotropic agents: stimulates cardiac contractility (ex. digoxin, PDE3i, beta agonists)
- Renin/angiotensin system inhibitors: Decreases preload and afterload
How can you tell if a Frank-Starling curve is representing a heathy person or someone with HF? What effects do different HF drugs have on the Frank-Starling curve?
Frank-Starling relationship represents the concept that as the LV end-diastolic volume (aka preload) increases, the stroke volume will increase. Stoke volume is also increases when inotropy (force of contraction) increases.
Compared to a healthy heart, a failing heart will have a lower frank-starling curve.
Afterload and SV are inversely related. As afterload increases, stroke volume decreases. Again, a failing heart will have a lower F-S curve than a healthy heart.
What is the pathophysiology of HF, including the importance of cardiac remodeling and compensatory changes in autonomic nervous system function?
HF is a progressive disease of compensation and decompensation. It has many different causes.
- HFrEF is systolic failure (muscle weakened) and HFpEF is diastolic failure (fibrosis)
There are 3 types of cardiac remodeling:
1. Cardiac dilation - myocyte length > width, can be due to an MI or other insults to the heart, see fibrosis and myocyte death. This is very serious (end stage).
2. Pathological hypertrophy - myocyte length < width, can be due to HTN and aortic valve stenosis, see fibrosis, and can progress to HF.
3. Physiological hypertrophy - optimal muscle growth, can be due to chronic exercise or pregnancy, there’s no fibrosis, and this results in an increase of muscle mass/function.
In the short term, increased cardiac work causes HTN and sympathetic stimulation (more Ca2+). In the long term, this causes increased Ca2+ cycling, which leads to Ca2+-dependent apoptosis, and results in replacement of myocytes with fibroblasts.
Compensatory mechanisms - Help in the short term to increase SV, but eventually cardiac output gets lower and afterload gets higher
1. Sympathetic discharge
2. Renin release
3. Cardiac remodeling
What MOA do these drugs have: cardiac glycosides, PDE3i, β-AR agonists, RAAS inhibitors, diuretics, β-AR blockers, vasopressin antagonists, neprilysin inhibitor (molecular/cellular and physiological level and how it relates to the efficacy of the drug)
cardiac glycosides - ex. digoxin, ouabain; These block the Na+/K+ ATPase, which will increase the intracellular Na+ concentration. Increased Na+ will decrease Ca2+ removal. Therefore, more Ca2+ is reloaded into intracellular stores, more Ca2+ is released in response to stimulation, and muscle contracts with greater force. BUT there’s a risk of remodeling, so this isn’t a long-term solution.
PDE3 inhibitors - ex. milrinone, amrinone; These block the breakdown of cAMP, which activates more PKA, which results in increased intracellular Ca2+ concentration, increasing force of contraction, thus increasing stroke volume.
β-AR agonists - ex. dopamine, dobutamine; These increase stimulation of GPCRs that results in more Ca2+ in the cell.
renin/angiotensin inhibitors - ex. ACEi, ARB, renin inhibitor; Reduce formation of angiotensin II, which would cause aldosterone and ADH to be secreted, which would cause H2O retention & increased sympathetic activity.
diuretics - aldosterone antagonists reduce aldosterone, which reduces salt and water retention, which decreases blood volume.
β-AR blockers - ex. carvedilol, metoprolol, bisoprolol; β1- blockers limit myocyte contraction and slow the pacemaker cells in the heart. These counter increased sympathetic drive, hear workload, and adrenergic tone. Also counter hypertrophic remodeling.
vasopressin antagonists - block vasopressin (ADH) receptors, thus reducing water retention, vasoconstriction, platelet aggregation, and VSM/myocyte proliferation.
neprilysin inhibitor- increases levels of vasoactive peptides, which counters neurohumoral vasoconstriction, Na+ retention, and remodeling.
Which HF drugs are used in acute vs chronic HF, whether or not it would be expected to arrest or reverse cardiac remodeling, what toxicities it has, and whether or not that drug will prolong the patient’s life?
cardiac glycosides - (digoxin) used chronically, but not super long-term, as they can cause remodeling. These do not improve mortality, but they do improve pumping and pressure problems. Has very narrow therapeutic index. Can cause psych (delirium, fatigue), GI (anorexia, N/V), respiratory (increased response to hypoxia), and CV (pro-arrhythmic) toxicities.
PDE3 inhibitors - (milrinone, amrinone) used acutely. These do not improve mortality, but improve pressure & pumping problems. These are pro-arrhythmic and are associated with decreased survival.
β-AR agonists - (dobutamine, dopamine) used acutely. These improve pressure & pumping problems, but cause HTN long term and are prone to desensitization. These have no effect on mortality.
renin/angiotensin inhibitors - (ACE inhibitors like enalapril, ARBs like losartan, renin inhibitors like aliskiren) Used chronically. These stop and reverse remodeling. These alleviate pressure and volume problems. May cause angioedemia.
diuretics - (loop diuretics like furosemide, K+ sparing like spironolactone) These arrest and reverse hypertrophy. They also decrease blood volume.
β-AR blockers - (carvedilol, metoprolol, bisoprolol) Used in early stage HF. These decrease remodeling and reduce mortality in CHF. These inhibit sympathetic overactivity in CHF.
vasopressin antagonists - Used acutely.
neprilysin inhibitor - Counters neruohumoral vasoconstriction, Na+ retention, and remodeling. Used with an ARB (sacubitril/valsartan)
What are the mechanisms of calcium cycling in myocyte contraction?
- Ca2+ ATPase: Uses ATP to pump Ca2+ out of cytosol
- SERCA: (sarco/endoplasmic reticulum Ca2+/ATPase) uses ATP to pump Ca2+ out of cytosol and into the sarcoplasmic reticulum lumen
- NCX: Sodium-calcium exchanger. This doesn’t use ATP and is a MAJOR ROUTE!! Ca2+ is pumped out of cytosol and Na+ is pumped into cell
- Na+/K+ ATPase: Pumps Na+ out and K+ in (need to get the Na+ from NCX out of the cell)
What are the etiologies of HF? Which are associated with HFrEF and HFpEF?
HFrEF - a pumping issue (systolic) that is due to decreased contractility. Caused by dilated ventricles, which could be due to ischemic dilated cardiomyocytes (most common), non-ischemic dilated cardiomyocytes, or other causes (like HTN, obesity, stress, etc.)
- EF < 40%
HFpEF - a filling issue (diastolic) that is due to impairment in ventricular relaxation/filling. Most commonly caused by HTN.
- EF > 50%
(ejection fraction = ratio of stoke volume & end diastolic volume)
What parts of a patient’s PMI and current clinical findings would allow us to identify the patient’s most likely etiology of HF?
- HTN, CAD, DM
Lab assessment -
- EF <40% = HFrEF
-EF >50% = HFpEF
What non-drug and drug factors may result in precipitation and/or cause HF?
Non-drug: lack of compliance (with diet, drugs, or both), uncontrolled HTN, cardiac arrhythmias, etc.
Drug:
- Negative inotropes: antiarrhythmics, b-blockers, nonDHP CCBs
- Direct cardiac toxins: Doxorubicin, 5-FU, Imatinib, ethanol, cocaine, etc.
- Drugs that increase Na+ and H2O retention: Glucocorticoids, NSAIDs, Sodium containing drugs
What compensatory mechanisms occur in HF and how do they each become detrimental?
Increased preload - Good to optimize stroke volume, but causes pulmonary/systemic congestion and edema, and increased oxygen consumption.
Vasoconstriction - Good to maintain BP while there’s reduced cardiac output, but caused increased oxygen consumption, the increased afterload decreases stroke volume, and it further activates the compensatory mechanisms.
Tachycardia & increased contractility - Good to maintain cardiac output, but increases oxygen consumption, causes b-receptor down regulation and decreased responsiveness, causes ventricular arrhythmias, and increases risk of myocardial cell death.
Ventricular hypertrophy & remodeling - Good to maintain cardiac output, reduce myocardial wall stress, and reduces oxygen consumption, but results in diastolic/systolic dysfunction, increases risk of myocardiac cell death/ischemica, increases risk of arrhythmias, and causes fibrosis.
How would a patient with HF present? How can we differentiate between right and left-sided HF, HFrEF, and HFpEF?
Shortness of breath, swelling of feet & legs, chronic lack of energy, difficulty sleeping at night due to breathing problems, swollen or tender absomen with loss of appetite, cough with frothy sputum, increased urination at night, confusion and/or impaired memory
Right:
- Symptoms: abdominal pain, anorexia, nausea, bloating, constipation
- Signs: peripheral edema, JVD, HJR, hepatomegaly, ascites
Left:
- Symptoms: DOE, orthopnea, PND, tachypnea, bendopena, cough, hemoptysis
- Signs: Rales, S3 gallop, pulmonary edema, pleural effusion, Cheyne-Stokes respiration
What are the classifications and stages of HF?
NYHA Classifications:
I. Patients have cardiac disease, but no symptoms
II. Patients with cardiac disease that results in slight limitations of physical activity
III. Patients with cardiac disease that results in definite limitations of physical activity
IV. Patients with cardiac disease that results in symptoms at rest and inability to be physically active
Stages:
A. At high risk for developing HF, but no s/s (ex. HTN, CAD, DM, etc.)
B. Structural heart disease that is strongly associated with HF, but no s/s of HF
C. Current or prior symptoms of HF associated with underlying structural heart disease
D. Advanced structural heart disease and marked symptoms of HF at rest, despite maximal medical therapy & those who require specialized interventions
What are goals/measures we use to treat all HFrEF/rEF patients?
- Treatment depends on the patient’s stage/class
For both asymptomatic rEF & HFrEF:
1. Slow disease progression
2. Reduce s/s and improve QOL and prevent/reduce hospitalizations and the need for emergency care
3. Reduce mortality
General measures:
- Treat underlying causes
- Remove precipitating causes
- Exercise (with caution); Want 20-60mins 3-5x/week
- Reduce sodium to 2-3g/day
- Alcohol reduction to 1 or 2 drinks per day
- Fluid restriction <2L/day if hyponatremic or if diuretics aren’t controlling volume
- Monitor weight
- Smoking cessation
- Immunizations
What are the advantages and disadvantages of using these drugs to treat HFrEF: diuretics, ACEIs/ARBs, ARNIs, b-blockers, MRAs
Diuretics - Reduces intravascular volume, only take when symptomatic, keep pts out of the hospital, but does not reduce mortality
Spironolactone - Blocks aldosterone release, reduces mortality
Positive inotropes - Increase myocardial contractility, but don’t reduce mortality.
ACEi/ARB - Decrease ventricular afterload, block RAAS, reduces mortality
ARNIs - Block RAAS, reduces mortality
Vasodilators - Decrease ventricular afterload, ISDN/hydralazine reduces mortality
Beta blockers - Neurohormonal blockade, reduces mortality
How would we formulate a plan to treat HF patients based on presence or absence of symptoms, HF etiology, individual characteristics, etc.?
If no symptoms, no HF, just at high risk for developing HF: Use ACEi if ASCVD
If no symptoms, but has have structural heart disease that’s strongly associated with HF: Use ACEi and/or beta-blocker if past hx of MI or asymptomatic rEF
If current or prior symptoms associated with HF (rEF) + beyond: Use ARNi, ACEi, or ARB (ACEi/ARB if NYHA class IV), beta blocker, MRA, SGLT2i, and diuretic as needed
- Once doses have been optimized, if pts still have symptoms, can consider hydralazine/ISDN in AA patients, ivabradine if pt still has HR >70 on max b-blocker dose
What are the benefits and potential problems with using ACEIs, ARBs, and ARNIs in heart failure? How do these agents play different roles in whether or not the pt has HFrEF or asymptomatic rEF?
These agents improve symptoms, decrease hospitalizations, improved exercise intolerance, and reduce mortality. We see benefits regardless of etiology or severity of disease, and they MUST be used in all patients who aren’t contraindicated.
- Also additional benefit in patients with IHD, CKD, post-MI, and DM
- Cannot use if the patient is pregnant or planning to get pregnant
- Need to look out for symptomatic hypotension & other adverse effects
What changes would we want to make to a pts HF treatment in order to affect the pt’s morbidity and mortality?
- Want to replace current ACEi/ARB with an ARNI when possible in order to further reduce mortality (can’t use ARNI if pt had angioedema with ACEi, but CAN use ARB if pt had angioedema with ACEi [need to monitor closely])
These agents reduce mortality: ACEi/ARB/ARNI, MRA, SGLT2i, beta-blocker, hydralazine/ISDN
What are the benefits and potential problems with using beta blockers in symptomatic HFrEF and asymptomatic rEF? How would we use these to maximize benefits and reduce adverse effects associated with their use?
Beta blockers (carvedilol, metoprolol succinate, and bisoprolol) have been shown to reverse remodeling. They provide symptom relief, improve QOL, reduce hospitalizations, and reduce mortality.
- Before initiating, pts need to be euvolemic
- Do not abruptly d/c
Double the dose of these every 2 weeks, but monitor very closely for symptoms.
Why do we use diuretics in pts with symptomatic HF? How do we initiate loop diuretics?
Diuretics reduce hospitalizations for HF patients. They reduce the symptoms associated with fluid overload, improve exercise tolerance, and improve quality of life.
For this reason, all patients with s/s of fluid retention should be on a diuretic. Patients who do not have volume overload symptoms should NOT receive diuretics.
- If patient has kidney damage, diuretics probs won’t work as well. Also, they won’t work as well as patients are taking them due to decreasing the patients blood volume.
- We really only use ethacrynic acid if pt has a severe sulfa allergy)
We use thiazide diuretics if patients have mild HF. These lose effectiveness as renal function decreases. Often used in combo with a loop diuretic in pts who become resistant to single-drug therapy.
Initiation:
- Initiate at low-doses, then double and titrate to symptoms
- If pt is fluid overloaded, we want to reduce their weight by 1-2lbs/day
- Dose adjustment may be needed during ACEi/ARNi/ARB or b-blocker initiation
What is the role of aldosterone antagonists and SGLT2 inhibitors in HF?
Aldosterone antagonists - prevents aldosterone effects (sympathetic activation, parasympathetic inhibition, cardiac/vascular remodeling). These can decrease the LOSS of K and Mg, decrease Na retention, decrease sympathetic stimulation, and block the direct fibrotic action on the myocardium.
- Sprionolactione is non-selective, eplerenone is selective
- Use for Stage C patients
SGLT2i - reduces myocardial remodeling, preload, and afterload. These are used to reduce the risk of CV death or hospitalizations for HFrEF pts.
What is digoxin’s role in HF in patients with normal sinus rhythm? How would we use these therapeutically safely and effectively?
Digoxin provides benefits due to its neurohormonal modulation effects. It increases parasympathetic activity. Also binds to Na+/K+/ATPase contraction-coupling, while increases intracellular Ca2+, enhancing force of contraction.
Digoxin is effective in reducing hospitalizations, but not mortality. We would consider dig in patients who are symptomatic, despite being optimized. We would add digoxin before hydralazine/ISDN.
What is the role of ISDN/Hydralazine in patients with HF? How would we use these therapeutically safely and effectively?
- Causes reductions in preload and afterload. Reduces mortality.
- Good for the african american patients who are NYHA class III or IV (very sick) and are also receiving max therapy of other HF drugs.
- Good for patients with symptoms who can’t receive ARNi/ACEi/ARB due to drug intolerance or renal insufficiency
- AEs are a significant problem and major limiting factor in clinical trials.
Recommended oral doses:
BiDil (ISDN/Hydralazine): 20/37.5mg TID -> 40/75mg TID
What are the monitoring parameters and adverse effects of these agents: diuretics, digoxin, ACEIs, ARBs, ARNIs, b-blockers, MRAs, SGLT2s
diuretics - low Mg, K+, Na+, volume depletion, orthostatic hypotension, increase uric acid, increased or decreased Ca2+
- Monitor these after 1-2 weeks of initiation or increase: fluid intake/urinary output, body weight, s/s of congestion, JVD, BP, electrolytes, renal function
digoxin - anorexia, N/V, abdominal pain, visual disturbances, PCVs, AV block, arrhythmias, bradycardia, etc.
- Monitor serum digoxin conc. due to narrow therapeutic index
ACEIs/ARBs/ARNIs - angioedema, acute kidney failure, hyperkalemia, hypotension, cough (ACEi); ARNIs can cause more hypotension, but angioedema is rare.
- Monitor renal function and potassium prior to therapy, 1-2 weeks after each dose increase, then at 3-6 month intervals. Also when other treatments are added that may impact renal function.
b-blockers - Bradycardia, dizziness, hypotension, fatigue, sexual dysfunction, depression
- Monitor BP and HR 1-2 weeks after initiation. If needed, reduce the dose by 50% and try to titrate again. If only hypotension is experienced, reduce other drugs before reducing the beta blocker. Edema, fluid retention, fatigue/weakness.
MRAs - impotence, menstrual irregularities, hyperkalemia, gynecomastia (spironolactone)
- Monitor renal function and K+ within 3 days-1 week
SGLT2s - volume depletion, ketoacidosis in DM, hypoglycemia, infection risk
What are the similarities and differences in the treatment of HFrEF vs. HFpEF?
The most important thing for HFpEF is aggressively treating BP to less than 130/80.
- Diuretics should be used for volume relief
- SGLT2i may reduce hospitalizations and CV mortality
- Management of AF in HFpEF pts can improve symptomatic HF
- Diruetics as needed
- SGLT2i
- ARNi, MRA, ARB
*ACEi/ARBs don’t reduce mortality here, but reduce hospitalizations
*don’t use dig
What are the approximate IV equivalents for loop diuretics? What is the bioavailability for those agents?
Furosemide 40mg = Bumetanide 1mg = Torsemide 20mg = Ethacrynic acid 50mg
Furosemide = 50%
Bumetanide = 100%
Torsemide = 100%
Ethacrynic acid = 100%
What are the approximate ACEi equivalents? How do we initiate an ARNi based on the patient’s previous ACEi/ARB dose?
Enalapril 20mg/day = Captopril 150mg/day = Lisinopril 20-40mg/day
If on high-dose ACEi (>10mg daily enalapril) or high-dose ARB (>160mg total daily valsartan) = starting dose is S 49mg/V 51mg BID
If on low/medium dose of ACEi/ARB, or if ACEi/ARB naive, or eGFR < 30, moderate hepatic impairment, or if older than 75 years old = S 24mg/V 26mg BID
**remember not to start ARNI w/in 36 hours of ACE/ARB use
How do we dose-adjust for kidney function with MRAs?
**should not be given with CrCL < 30mL/min, SCr >2.5, or K+ >5
Spironolactone:
Normal dosing starts at 12.5-25mg QD and the target dose is 25mg QD
When CrCL is 30-49: starting dose is 12.5mg QD or QOD; the target dose is 12.5-25mg QD
Eplerenone:
Normal dosing starts at 25mg QD and the target dose is 50mg QD
When CrCL is 30-49: starting dose is 25mg QOD and target is 25mg QD
Why/when would you use ivabradine during HF treatment? What are the adverse effects?
Ivabradine reduces risk of hospitalization for symptomatic HF (EF <35%) when HR is > 70 while maxed out on a beta-blocker (or if contraindicated).
- Dose adjust to heart rate
AEs: fetal toxicity, atrial fibrillation, bradycardia, conduction disturbances
Why/when would you use vericiguat during HF treatment? What are the adverse effects?
Vericiguat reduces CV death/hospitalizations (is a sGC stimulator). Consider in high-risk patients with recent worsening symptomatic HFrEF, despite GDMT, to decrease hospitalization for HF and CV death.
*CI in pregnancy
AEs: hypotension, anemia
How can you identify key ion channels that account for the major current flow during the phase of nodal/myocyte action potential (0-4).
Myocytes:
Phase 0 - Na+ channel depolarization. Na+ floods into the cell. (also Ca2+ enters cell)
Phase 1 - Na+ channel closes
Phase 2 - K+ channels open, K+ exits the cell. (Ca2+ enters cell, late Na+ enters cell). Plateau phase
Phase 3 - Lots of K+ leaves the cell
Phase 4 - Back to resting potential, some leaky K+ channels allow K+ to exit cell.
Nodal cells:
Phase 0 - Ca2+ enters cell towards the threshold, funny channels are open
Phase 3 - K+ channels repolarize, K+ leaves cell
Phase 4 - funny channels open, K+ leaves cell due to activation by the vagus nerve
**ventricular myocytes are dependent on Na+, but the pacemaker cells (SA/AV node) depend on Ca2+ spikes.
How can you predict whether the change in action potential (due to arrhythmia or drug) will be proarrhythmic or antiarrhythmic?
Antiarrhythmic drugs:
- Na+ channel blockers: Class 1A has a mixed Na/K block that prolongs the QT interval, Class 1B only blocks Na+ and has no effect on ECG, Class 1C is a strong Na+ block, which widens the QRS and slows the depolarization of Na+ channels
- beta blockers will push the action potential to the right. these prevent arrhythmias due to catecholamines
- K+ channel blockers will prolong action potential duration & increases the effective refractory period. Increasing EFR terminates re-entry
- Ca2+ channel blockers will lower the peak of the action potential
What can certain changes in cardiac action potential do to the ECG?
Class 1A Na+ channel blockers - prolong QT interval
Class 1B Na+ channel blockers - do nothing
Class 1C Na+ channel blockers - widen QRS complex
beta-blockers slow the heart rate
K+ channel blocker prolong QT interval
How do these specific antiarrhythmic agents exhibit selectivity to either atrial or ventricular tissues? If applicable, how does it have a greater effect in arrhythmogenic cells?: Na+ channel blockers, beta adrenergic antagonists, K+ channel blockers, Ca2+ channel blockers
Na+ channel blockers -
Class 1a: quinidine
Class 1b: lidocaine, mexiletine; only ventricular tissues
Class 1c: flecainide; only ventricular and supraventricular
beta adrenergic antagonists - propranolol, metoprolol; unclear if atrial or ventricular, just know we want cardioselective
K+ channel blockers - amiodarone is atrial & ventricular, ibutilide is atrial, sotalol is atrial & ventricular, and dofetilide is atrial
Ca2+ channel blockers - verapamil, diltiazem; cardioselective (idk atrial/ventricular)
What is the MOA at the molecular level for these agents: Na+ channel blockers, beta adrenergic antagonists, K+ channel blockers, Ca2+ channel blockers, digoxin, adenosine
Na+ channel blockers - block the Na+ channels, thus inhibiting Na+ from entering the cell, slowing the rate of contraction.
beta adrenergic antagonists - block beta receptors, which is usually stimulated by NE, then increases cAMP & PKA, which would increase the HR. Now that it’s blocked, HR is decreased.
- esmolol, acebutolol, propanolol
K+ channel blockers - block potassium channels to lengthen action potential
Ca2+ channel blockers - Blocks the calcium influx, which is frequency dependent. The heart rate & contractility is decreased from this.
digoxin - inhibits the AV node
adenosine - depresses pacemaker cells, similar to M2 activation
What toxic side effects do these drugs cause: Na+ channel blockers, beta adrenergic antagonists, K+ channel blockers, Ca2+ channel blockers
Na+ channel blockers -
Class 1a: quinidine; Torsades de Pointes
Class 1b: lidocaine, mexiletine
Class 1c: flecainide
beta adrenergic antagonists - hypotension, dizziness, fatigue, bradycardia
K+ channel blockers - admiodarone may cause hypothyroidism, pulmonary fibrosis, photosensitization; blocking HERG channels can cause acquired long QT syndrome
Ca2+ channel blockers - hypotension, dizziness, fatigue
What are the normal time intervals for the PR interval, QRS duration, QT interval, and QTC interval (men and women)?
PR interval: 120-200ms (measure of AV nodal conduction time)
QRS duration: 80-120ms (sodium channels)
QT interval: 380-460ms (potassium channels)
QTc interval-men: 360-450ms (corrected for HR)
QTc interval-women: 360-460ms (corrected for HR)
What is torsades de pointes? What are some common drugs & drug classes that cause it?
When the QTc interval is more than 500ms, there is risk for torsades de pointes (drug-induced). This means ventricular repolarization is being prolonged too much. This can cause sudden cardiac death.
- Antiarrhythmic agents (ex. procainamide, sotalol, amiodarone)
- Antimicrobials (macrolides like azithromycin, fluoroquinolones)
- Antidepressants (citalopram, ecitalopram)
- Antipsychotics (ex. haloperidol, olanzapine)
- Anticancer (most drugs ending in -nib)
- Opioids (methadone)
What are different risk factors for each of the arrhythmias?
sinus bradycardia - MI, hyperkalemia, hypermagnesemia, drugs (digoxin, b-blockers, CCBs, amiodarone, dronedarone, ivabradine)
AV block -
sinus tachycardia -
atrial fibrillation - hypertension, CAD, HF, valvular heart disease, hyperthyroidism, PE, thoracic surgery, alcohol use
supraventricular tachycardia - gender (female), older than 65 years old
PVCs - Ischemic heart disease, MI, anemia, hypoxia, cardiac surgery
ventricular tachycardia - CAD, MI, HFrEF, electrolyte abnormalities, drugs (flecainide, propafenone, digoxin)
ventricular fibrillation - MI, HFrEF, CAD
What are the features, mechanisms, etiologies, symptoms, and goals of treatment for sinus bradycardia?
Features - Heart rate below 60bpm, impulses originate in the SA node
Mechanism - Decreases automaticity of the SA node, so it generates impulses slower than it should. (no re-entry happening)
Etiology - MI, ischemia, abnormal sympathetic/parasympathetic tone, electrolyte abnormalities (hyperkalemia, hypermagnesemia), drugs (ex. b-blockers, CCBs)
Symptoms - hypotension, dizziness, syncope
Goals of treatment - Treatment only necessary if pt is symptomatic
What are the features, mechanisms, etiologies, symptoms, and goals of treatment for atrial fibrillation?
Features - Chaotic & disorganized atrial activity due to no atrial contractions, ventricular rate of 120-180bpm, irregularly irregular rhythm, absent P-waves
Mechanism - abnormal atrial/pulmonary vein automaticity that then leads to atrial re-entry
Etiologies - hypertension, CAD, HF, valvular heart disease
Symptoms - could be asymptomatic, palpitations, dizziness, fatigue, SOB, angina (if pt has CAD), exacerbation of HF symptoms
Goals of treatment - HR <110bpm; if symptomatic or HFrEF, HR <80bpm
- Persistent AF: ventricular rate control, prevention of stroke/systemic embolism, conversion to sinus rhythm
- Paroxysmal AF: ventricular rate control, prevention of stroke/systemic embolism, maintenance of sinus rhythm
- Permanent AF: ventricular rate control, prevention of stroke/systemic embolism
What are the features, mechanisms, etiologies, symptoms, and goals of treatment for supraventricular tachycardia?
Features - regular rhythm, narrow QRS complexes, heart rate 110 -> 250bpm, spontaneous initiation and termination, P & T waves may blend together; Can be paroxysmal
Mechanisms - involves re-entry within the AV node (60%), accessory pathway, atria, and/or SA node.
Etiologies - Occurs more often in women, people over 65 years old, and often occurs in individual with not cardiovascular disease.
Symptoms - “neck-pounding,” palpitations, dizziness, weakness, lightheadedness, near-syncope, syncope, polyuria
Goals of treatment - terminate SVT, restore sinus rhythm, prevent recurrences. (SVT is not threatening, and doesn’t cause stroke because the atria are still contracting)
What are the features, mechanisms, etiologies, symptoms, and goals of treatment for premature ventricular complexes?
Features - Wide QRS complexes, only 0.8% prevalence in the healthy population. Prevalence increases with advancing age. Can be simple, pairs (couplets), every 2nd-4th beat (bigeminy, trigeminy, quadrigeminy), and frequent (at least one PVC on a 12-lead ECG, >30 PVCs per hour).
Mechanisms - Increases automaticity of ventricular muscle cells/Purkinje fibers
Etiologies - Ischemic heart disease, MI, anemia, hypoxia, cardiac surgery
Symptoms - Usually asymptomatic, frequent/repetitive PVCs may cause paltipations, dizziness, and lightheadedness
Goals of treatment - do not treat if asymptomatic. Goals of treatment are to reduce symptoms, since treating PVCs have not shown to improve mortality.
What are the features, mechanisms, etiologies, symptoms, and goals of treatment for ventricular tachycardia?
Features - Regular rhythm, wide QRS complexes, defines as a series of ≥ 3 consecutive PCVs at a rate of over 100bpm. These PVCs are monomorphic. VT can be nonsustained where it terminates spontaneously OR sustained, where the VT lasts longer than 30 seconds or it requires termination due to hemodynamic instability OR sustained monomorphic, where the pt doesn’t have any structural heart disease.
Mechanisms - increased ventricular automaticity, reentry
Etiologies - CAD, MI, HFrEF, electrolyte abnormalities, drugs (flecainide, propafenone, digoxin)
Symptoms - may be asymptomatic, palpitations, hypotension, dizziness, lightheadedness, syncope, angina
Goals of treatment - terminate VT, restore sinus rhythm, prevent recurrence of VT, reduce the risk of sudden cardiac death
What are the features, mechanisms, etiologies, symptoms, and goals of treatment for ventricular fibrillation?
Features - Irregular, disorganized, chaotic electrical activity with no recognizable QRS complexes
Mechanisms -
Etiologies - MI, HFrEF, CAD
Symptoms - sudden cardiac death/collapse
Goals of treatment - terminate ventricular fibrillation, restore sinus rhythm and spontaneous circulation (ROSC)
- The only effective treatment is defibrillation. Drugs are used to facilitate defibrillation, but cannot terminate VF on their own.
What are the non-pharm and pharm treatment options for sinus bradycardia?
non-pharm:
- permanent pacemaker
pharm:
- atropine
- if unresponsive to atropine: dopamine, epinephrine, isoproterenol
- if heart transplant or spinal cord injury: aminophylline, theophylline
What are the different definitions of atrial fibrillation?
Paroxysmal - intermittent episodes of AF. The episodes start suddenly and spontaneously, last for minutes to hours, and terminate suddenly and spontaneously.
Persistent - a continuous episode of AF that does not terminate spontaneously
- Could last more than 7 days
Long-standing persistent - continuous AF for longer than 12 months
Permanent - AF is always present. The patient is never again in sinus rhythm. This term is used when the patient and the provider make the decision to stop further attempts to restore sinus rhythm.
Nonvalvular - AF in the absense of rheumatic mitral valve stenosis, a mechanical or biprosthetic heart valve, or mitral valve repair
What are the different mechanisms of the drugs that are used for ventricular rate control in patients with atrial fibrillation?
Diltiazem - Direct AV node inhibition; May cause hypotension, HF exacerbation, bradycardia, and AV block
Verapamil - Direct AV node inhibition; May cause hypotension, HF exacerbation, bradycardia, and AV block
Beta-blockers - Direct AV node inhibition; May cause hypotension, bradycardia, HF exacerbation (if dose is too high), and AV block
Digoxin - Direct AV node inhibition & vagal stimulation; May cause N/V, anorexia, ventricular arrhythmias; If used with amiodarone, need to reduce dig dose by 1/2 & get blood conc. done afterwards
Amiodarone - beta-blocker and CCB action; the 1/2 life is very long, which makes it difficult to use for rate control; may cause hypotension, bradycardia, photosensitivity; inhibits CYP450
What are the different mechanisms of the drugs that are used to convert to sinus rhythm and maintenance of sinus rhythm in patients with atrial fibrillation?
*If AF has been present for less than 48 hours, converting to sinus rhythm is safe. If longer than 48 hours, we need to make sure there is no clot before converting to sinus rhythm.
Converting to sinus rhythm:
DC cardioversion - spontaneously depolarizes all myocardial cells, allowing sinus node to take over as the pacemaker. Do immideately if pt is hemodynamically unstable.
Amiodarone - Class I-IV, meaning it blocks Na+, K+, and Ca2+ channels, and beta receptors; Risk of bradycardia and hypotension (caution with digoxin)
Dofetilide - Class III, meaning it blocks K+ channels; oral dosing is important due to risk of torsades de pointes
Ibutilide - Class III, meaning it blocks K+ channels; only used in hospital; risk of torsades de pointes
Propafenone - Class IC, meaning it strongly blocks Na+ channels; Risk of HF exacerbation, so do not give to HF patient; Pill in the pocket
Flecainide - Class IC, meaning it strongly blocks Na+ channels; Risk of HF exacerbation, so do not give to HF patient; Pill in the pocket
Maintaining sinus rhythm:
Amiodarone, dofetilide, propafenone, flecainide
Dronedarone - Class III, meaning K+ channel blocker; risk of torsades de points, commonly used to maintain sinus rhythm, interacts with digoxin
Sotalol - beta-blocker; risk of torsades de pointes
What are the options for non-pharm therapy of atrial fibrillation and acute SVT and when would you select certain non-pharm/pharm options to treat these?
DCC - direct cardioversion to convert to sinus rhythm
Catheter ablation - to maintain sinus rhythm
Converting to sinus rhythm: DCC is always the go-to, but not always possible. Then we move to pharm therapy (amiodarone, dofetilide, ibutilide, flecainide, propafenone).
Maintaining sinus rhythm: Catheter ablation & drug therapy are equally favored (dofetilide, dronedarone, sotalol, flecainide, propafenone -> amiodarone).
Why is anticoagulation important for patients with atrial fibrillation?
The blood may have been stationary in the atria for a prolonged period of time, which could’ve caused a clot to form. We can’t risk that clot getting into the brain and causing a stroke, so we heavily rely on anticoagulants to dissolve these.
We look at the CHADS2-VASc score to determine which patients get anticoagulation. If the score is ≥ 2 in men and ≥ 3 in women, oral anticoagulants are recommended. MAY be considered if score is 1 in men or 2 in women
What are the different drug therapy options for anticoagulation with a fib patients?
*NOACs preferred over warfarin for NOAC-eligible patient with AF, UNLESS they have a mechanical heart valve (INR 2.5-3.5) or valvular AF (INR 2-3).
**Warfarin OR apixaban is preferred if pt has ESRD (CrCL <15mL/min) or on hemodialysis.
NOACs - dabigatran, rivaroxaban, apixaban, edoxaban
- apixaban is the only option if CrCL < 15mL/min
- all NOACs are pgp substrates
What are the MOAs for the drugs used to acutely terminate SVT?
Adenosine - Inhibits AV node conduction, which terminates reentrant pathway; Most commonly used, has 10 second half life, IV dosing (6, 12, 12); May cause transient chest pain, flushing, SOB, sinus pauses
beta-blockers - Inhibits AV node conduction, which terminates reentrant pathway; esmolol, propranlol, metoprolol
diltiazem - Inhibits AV node conduction, which terminates reentrant pathway
verapamil - Inhibits AV node conduction, which terminates reentrant pathway
What is the non-pharm therapy that is used for long-term prevention of recurrence of SVT?
- catheter ablation (burning out of pathway of the AC node)
What is the role of drug therapy for long-term prevention of recurrence of SVT?
Drug therapy is only used if the patients are symptomatic and if catheter ablation isn’t wanted.
If no HFrEF: beta-blockers, diltiazem, verapamil -> if no CAD, then can try flecainide or propafenone if first agents did not work.
If yes HFrEF: amiodarone, digoxin, dofetilide, sotalol
What is the role of drug therapy for management of asymptomatic and symptomatic PVCs?
We do not treat asymptomatic PVCs
Symptomatic:
- If no CAD or HF, can use b-blockers, diltiazem, or verapamil; if that doesn’t work, then try antiarrhythmic medication; if PVCs are more than 15% of beats and pt is unresponsive to drugs, we can do catheter ablation.
- If yes CAD: b-blockers, diltiazem, or verapamil; try other antiarrhythmic meds if that doesn’t work
- If yes HF: use only b-blockers
What are the MOAs of the drugs used for the treatment of acute episodes of VT?
Convert to sinus rhythm:
procainamide - antiarrhythmic Class IA
amiodarone - antiarrhythmic Class I-IV (blocks everything)
sotalol - beta-blocker
verapamil - nonDHP CCB
beta-blockers - esmolol, metoprolol, propranolol
Prevent recurrence of VT & SCD
ICD - implantable cardioverter defibrillator (treatment of choice)
catheter ablation - recommended for pts with prior MI and recurrent episodes of VT & who have failed other treatment
amiodarone, sotalol (use for pts with ICDs who have significant symptoms)
What is the dosing for sotalol and dofetalide?
Sotalol - when initiating, QTc must be ≤ 450ms. Check QTc after 2-4 hours of first dose. If QTc > 500ms at any point, d/c. If QTc is fine after 3 days, patient can be discharged OR increase the dose to 120mg BID for 3 days (while monitored).
CrCL > 60mL/min: 80mg BID
CrCL 40-60mL/min: 80mg QD
CrCL <40mL/min: CONTRAINDICATED
Dofetalide - when initiating, QTc must be ≤ 440ms. Must check QTc after 2-3 hours of the first dose. If the QTc has increased more than 15% or to >500ms, need to 1/2 the dose. d/c if QTc is > 500ms after the 2nd dose.
CrCL > 60mL/min: 500mcg PO BID
CrCL 40-60mL/min: 250mcg PO BID
CrCL 20-39mL/min: 125mcg PO BID
CrCL < 20mL/min: CONTRAINDICATED
What are the options and indications for non-pharm treatment of VT and VF?
treatment of VT with SHD:
1. IV procainamide
2. DCC or IV sotalol or IV amiodarone
3. DCC
treatment of VT w/o SHD:
1. use verapamil if verapamil-sensitive
1. use b-blocker if outflow tract VT
2. DCC
treatment of VF: #1 is defibrillation
1. epinephrine: vasopressor
2. amiodarone: antiarrhythmic class I-IV
2. lidocaine: class 1B
What are the markers for when a patient is hemodynamically unstable?
- Systolic BP < 90mmHg
- HR > 150bpm
- Ischemic chest pain
- Loss of consciousness
immediately shock if any of these are occuring
**want to sedate pts if possible
**due to sedation, patients cannot have eaten before getting shocked, which is a common reason for postponing elective shock
What are the monitoring parameters and frequency for patients on amiodarone?
*amiodarone is used to convert to sinus rhythm & maintain sinus rhythm in atrial fibrillation
- Liver function tests at baseline and every 6 months
- Thyroid function tests (T4 and TSH) at baseline and every 6 months
- Chest X-Ray at baseline and annually
- Pulmonary function tests at baseline and for unexplained dyspnea
- Ophthalmologic exam at baseline and if visual impairments/symptoms occur
