Therapeutics I Exam V (CAD + HF) Flashcards
Acute coronary syndrome, chronic coronary syndrome, Ischemic Heart disease, HFrEF, and HFpEF
What is a STEMI?
This is an ST-elevated myocardial infarction
What are the two ways in which revascularization is performed in acute coronary syndrome?
- Cardiac catheterization with PCI
- Coronary artery bypass grafting (CABG)
What is the goal of a stress test?
The goal of a stress test via both exercise and pharmacologic intervention is to increase heart rate and see if there are any EKG changes.
Which cardiac tests allows for an estimation of left ventricular ejection fraction?
Echocardiogram
Define coronary artery disease (CAD)?
CAD is a condition where the arteries that supply blood to the heart become narrowed or blocked. This change is typically due to plaque accumulation.
What are the three disease states are encompassed into coronary artery disease (CAD)?
Ischemic heart disease
Stable/ chronic coronary artery disease
Unstable/acute coronary artery disease
What is acute coronary syndrome (ACS)?
A spectrum of clinical syndromes associated with the rupture of an atherosclerotic plaque and/or partial or complete thrombosis of a coronary artery.
Acute coronary syndrome (ACS) presents clinically as what 3 different things?
Unstable angina, NSTEMI, and STEMI
T or F: Acute coronary syndrome is a medical emergency.
True!
What is angina?
Angina is pain, discomfort, or pressure localized in the chest that is caused by ischemia to the heart muscle.
Are STEMIs or NSTEMIs more prevelant?
NSTEMIs are more prevalent (70%)
For unstable angina in acute coronary syndrome, what biomarkers are present?
No biomarkers will be positive if unstable angina is the diagnosis. Only STEMI and NSTEMI have positive biomarkers.
Myocardial oxygen demand is affected by what 3 things?
Heart rate, contractility, and intra-myocardial wall tension during systole.
Adenosine is a potent _______________.
Vasodilator
The endothelium of blood vessels secretes _________ and ___________.
Nitric oxide and Prostacyclins
Carbon dioxide is a vaso___________.
Vasodilator
What is the difference between stable and unstable plaque?
Stable plaques are characterized by a thick fibrous cap and a low lipid content, while unstable plaques, also known as vulnerable plaques, have a thin fibrous cap and a high lipid content.
Once a plaque ruptures, what happens to that floating plaque?
A thrombus will form on top of the ruptured plaque and exposure to collagen and tissue factor promotes platelet adhesion to the plaque.
_______% of acute coronary syndrome cases are due to plaque rupture.
90%
What are modifiable risk factors for plaque rupture leading to an acute coronary event?
Smoking, high cholesterol, and diabetes
What are non-modifiable risk factors for plaque rupture leading to an acute coronary event?
Cap fatigue, atheromatous core size, cap thickness, cap inflammation, homocysteine, impaired fibrinolysis, and fibrinogen.
What is a myocardial infarction?
An MI is impairment of blood flow due to a coronary occlusion. The coronary occlusion arises from a ruptured atherosclerotic plaque that becomes a thrombosis.
What are the biochemical damages that occur to the heart with a myocardial infarction?
- loss of mitochondrial ATP
- Increase in anaerobic glycolysis accumulating H+ and lactate
- Tissue acidosis
What are the functional damages that occur to the heart with a myocardial infarction?
- rapid loss of contractile function in affected area
- electrical abnormalities that may result in arrhythmias following repurfusion
- myocardial cell death
Myocardial cell death begins _____-_____ minutes after an occlusion. Cell death is complete in 3-6 hours following the occlusion.
20-30 minutes
What is cardiac remodeling?
Remodeling is the body’s attempt to compensate for loss of cardiac muscle. It changes the size, shape, and function of the left heart often resulting in cardiac failure.
What are the 4 contributing factors to cardiac remodeling?
- Activation of RAAS
- Sympathetic nervous system
- Hemodynamics
- Mechanical
Why is cardiac remodeling bad?
- Increased end-diastolic ventricular pressure and volume which decreases CO
- Increased ventricular pressure increases wall stress further impairing the ventricles
- Increased wall stress increases thickness of the wall
- Process continues until there is a balance between wall thickness and ventricular pressure
All this does is lead to cardiac cells being exposed to higher energy signals and demand leading to more cell death, wall stress, and neurohormonal response which progresses into heart failure.
Cardiac remodeling eventually progresses into cardiac __________.
Failure
What is one of the top causes of heart failure?
Acute coronary syndrome
T or F: NSTEMI can progress into a STEMI if left untreated.
True
T or F: NSTEMI is more severe than a STEMI.
False. NSTEMI is less severe as it is only a partial block while a STEMI is a full block of a coronary artery.
What are the 3 subjective signs of acute coronary syndrome?
- Rest angina (chest pain while at rest)
- Newly onset of severe angina (within the last 2 months)
- Increasing angina in either duration, intensity, or frequency
What are the main symptoms associated with acute coronary syndrome?
Chest pain, arm pain, lower jaw pain, SOB, diaphoresis, or it could have no symptoms.
What percentage of patients experiencing an ACS event will not have the ‘normal’ symptoms?
33%. These patients do not present with chest pain but may present with sweating, nausea, fatigue, etc.
What are the 4 populations in which silent MIs are most common?
Older, women, diabetes, and prior heart failure
What are the risk factors for increased mortality with angina?
Heart failure, smoking, left main CAD, diabetes, or prior MI
What is the difference between stable and unstable angina?
Stable angina symptoms are triggered by an activity and the symptoms are less severe and less frequent. Stable angina can also be treated medically. On the other hand, unstable angina can occur with or without triggers, has severe symptoms and it is a form of acute coronary syndrome that is an emergency and needs to be treated ASAP.
Typical angina results from a temporary imbalance of myocardial oxygen demand and supply. What are the other 3 characteristics that must be met to be diagnosed with typical angina?
- Substernal chest discomfort due to….
- Exertion or emotional stress
- That is fixed by rest or nitroglycerin
A typical chest pain meets _______ out of 3 characteristics in order to be diagnosed.
(Angina characteristics:)
1. Substernal chest discomfort due to….
2. Exertion or emotional stress
3. That is fixed by rest or nitroglycerin
2
What are other common conditions that can present with chest pain?
Aortic dissection, pericarditis, PE, costochondritis, rib fracture, esophagitis, peptic ulcer, panic disorder, and much more.
What are some conditions that can provoke and exacerbate ischemia?
Hyperthyroidism, cocaine use, HTN, anxiety, anemia, asthma, COPD
NSTEMI can have EKG changes. What are some of those EKG changes that may be present?
ST segment depression and/or an inverted T wave
What is the EKG changes seen in a STEMI?
ST elevation (comes from the name itself lol)
What lab is always drawn when someone presents with chest pain?
Troponins!!
What is the significance of troponin?
Troponin levels increase with cell death. If myocardial cells are dying due to a block or partial block, troponin levels should be elevated.
What is a common complication of acute coronary syndrome in patients?
Cardiogenic shock is the most common and it seen more in STEMI patients than NSTEMI patients.
T or F: No scoring system exists to evaluate patient risk for a major acute coronary event when presenting to hospital with chest pain.
False. There are many clinical scoring tools available to determine risk for a major acute coronary event in patients presenting to the ER with chest pain.
What are the immediate goals for care from someone presenting/diagnosed with NSTEMI or unstable angina?
- Immediate relief of ischemia
- Prevent serious adverse outcomes like death or reinfarction
What testing could be done for someone presenting with NSTEMI or unstable angina?
Left ventricle function could be assessed via an echocardiogram
Every patient presenting with chest pain should receive what medications?
What is the THROMBINS acronym and why it is used?
THROMBINS stands for thienopyridine (P2Y12 inhibitors), Heparins (IV anticoags), RAAS (ACE/ARB), oxygen, morphine, b-blocker, intervention (PCI or CABG), nitroglycerin (SL or drip), and statin + salicylate
This acronym incudes all the medications that may be used in early hospital admission for acute coronary syndrome.
Why is nitroglycerin always given upon hospital arrival NSTEMI or unstable angina?
Nitrates reduce myocardial oxygen demand by enhancing myocardial oxygen delivery. Any decrease in oxygen demand in the heart we can get is good!
What is the MOA of nitroglycerin?
Nitroglycerin works as a peripheral and coronary vasodilator. It also decreases cardiac preload which decrease ventricular wall tension and decreases oxygen demand.
Is sublingual or IV drip nitroglycerin preferred for the presentation of NSTEMI or unstable angina?
Sublingual is preferred at first. After 3 doses of sublingual nitroglycerin with no angina relief, IV drip nitroglycerin can be considerd.
What is the sublingual dosing for nitroglycerin?
0.3-0.4 mg Q5min for a maximum of 3 doses
When should IV or sublingual nitroglycerin not be used, even in cases of acute coronary syndrome?
If the patient has taken sildenafil or vardenafil within the last 24 hours or has taken tadalafil within the last 48 hours.
What 3 patient populations are indicated for IV drip nitroglycerin and not sublingual nitroglycerin?
- patients who have persistent ischemia
- heart failure
- hypertensive crisis
T or F: IV nitroglycerin is indicated for patients with NSTE-ACS for the treatment of persistent ischemia, heart failure, or hypertension.
True
What is the IV nitroglycerin dosing for NSTEMI or unstable angina?
5 mcg/min continuous infusion. This medication can be titrated up.
What is the most common side effect associated with nitroglycerin?
Headaches
What other medication can be given to patients presenting/diagnosed with NSTEMI or unstable angina when angina symptoms are not relieved by nitroglycerin?
Morphine
What are the 2 main functions of morphine?
- Pain relief
- Causes venodilation and modestly decreases heart rate and blood pressure
What is the IV dosing for morphine?
1-5 mg Q3-4H IV
What medications should absolutely be discontinued and/or avoided for patients presenting with NSTEMI or unstable angina?
NSAIDS!!!!!!! NSAIDs increase the risk for a major adverse cardiac event
This does not include aspirin tho lol
Beta blockers work in NSTEMI and unstable angina because they decrease what 4 things?
- Decrease myocardial oxygen demand
- Decrease HR
- Decrease myocardail contractility
- Decreases blood pressure
Beta blockers work in NSTEMI and unstable angina because they decrease myocardial oxygen demand, heart rate, blood pressure, and myocardial contractility. What do 3 other things do beta blockers do?
- Increases diastolic time (due to reduction in HR)
- Improves ventricular filling
- Improves coronary artery perfusion
Oral beta blockers need to be administered within the first _______ hour of hospital arrival for cases of acute coronary syndrome.
24 hours
Are oral or IV beta blockers preferred in cases of acute coronary syndrome?
Oral administered within the first 24 hours of hospital arrival
What are the 5 contraindications for beta-blocker use in cases of acute coronary syndrome?
- Signs of heart failure
- Evidence of low-output state
- Increased risk for cardiogenic shock
- Heart block
- Active asthma
Always reevaluate contraindications every 24 hours to determine if patient becomes eligible for beta blocker.
T or F: IV Beta blocker are not harmful in cardiogenic shock or if they are at risk for shock.
False. IV Beta blockers are HARMFUL is cardiogenic shock.
What is cardiogenic shock?
This is when the blood pressure drops very low due to their heart not pumping well.
Which 3 beta-blockers are recommended to be started in a patient with NSTEMI (stabilized heart failure and reduced systolic fxn)?
Carvedilol, Bisoprolol, or metoprolol succiante
What 3 beta-blockers are shown to reduce mortality in patients presenting with NSTEMI with stabilized HF and decreased systolic function?
Metoprolol succinate
Bisoprolol
Carvedilol
Are beta blockers contraindicated in those with COPD or with a history of asthma?
No. Beta-blockers are only contraindicated with active asthma or reactive lung disease.
When should ACEi/ARBs be started in patients presenting with NSTEMI or unstable angina?
All patients with LVEF < 40% AND in those with HTN, diabetes, or stable CKD.
T or F: ACE inhibitor use in patients presenting with ACS can still be considered even if they do not have with LVEF < 40%, HTN, diabetes, or stable CKD.
True. No harm will be done to the patient but there is limited data on mortality outcomes in this population.
What is the MOA of aspirin?
Irreversibly inhibits COX-1 preventing platelet aggregation for 7-10 days.
T or F: Aspirin reduces the risk of death and developing an MI by about 50% compared to no anti-platelet therapy.
True.
When patients present to the hospital with possible ACS, what medication needs to be given right away to ALL patients, assuming no contraindications?
NON-ENTERIC COATED CHEWABLE ASPIRIN (162-325mg)
followed by maintenance doses (81mg) of aspirin indefinitely.
What should a patient receive if they have a major intolerance or major GI intolerance (contraindication) to aspirin but show up to the hospital with ACS?
Clopidogrel loading dose followed by daily maintenance dosing.
T or F: Patients already taking daily aspirin at home before undergoing a PCI in the cath lab should not take an additional dose of a non-enteric coated aspirin before the PCI.
False. Patients should take an additional 81-325mg non-enteric coated chewable aspirin before undergoing the PCI
T of F: After an ACS event, a person can discontinue their low-dose aspirin after 1 year.
False. After an ACS event, aspirin is continued indefinetly.
Once acute coronary syndrome is officially diagnosed what other antiplatelet needs to be started in addition to aspirin?
In addition to aspirin, clopidogrel (plavix), prasugrel (effient), or ticagrelor (brilinta) should be started as well.
Ticagrelor and prasugrel are preferred.
What two antiplatelets are preferred for dual-antiplatelet therapy after the official diagnosis of an acute coronary event?
Ticagrelor and prasugrel are preferred but clopidogrel can be used. Ticagrelor is preferred with NSTEMI treated with early invasive strategy while prasugrel is preferred for NSTEMI patients who undergo PCIs.
What is the black box warning for prasugrel?
Do not give to those with previous stroke or TIA.
A loading dose of a _________ ____________ should be given prior to a patient undergoing PCI with stenting.
P2Y12 Inhibitor
Once ACS is officially confirmed (NSTEMI, UA, or STEMI) what are the two pathways for treatment?
Conservative pathway or early invasive pathway. The conservative approach includes optimal medical therapy with angiography deferred or guided by ischemia while the early invasive pathway includes early angiography and revascularization (PCI or CABG).
What medication should given given before a patient enters the cath lab for a PCI?
A loading dose of P2Y12 inhibitor (600mg clopidogrel, 60mg prasugrel, or 180mg ticagrelor)
How long will a patient be continued on a P2Y12 inhibitor after an ACS event?
A minimum of 1 year
Lets break it all down one more time, what antiplatelet therapy is given to a confirmed ACS patient undergoing a PCI in the cath lab?
Aspirin + Ticagrelor or Prasugrel
Lets break it all down one more time, what antiplatelet therapy is given to a confirmed ACS patient undergoing a CABG in the cath lab?
Aspirin + ticagrelor or clopidogrel
(aspirin is continued during CABG and P2Y12 is started after the surgery, no loading dose of P2Y12s here due to the very recent major surgery)
Lets break it all down one more time, what antiplatelet therapy is given to a confirmed ACS patient that is not undergoing an invasive evaluation (no PCI or CABG)?
aspirin + ticagrelor
Lets break it all down one more time, what antiplatelet therapy is given to a confirmed STEMI only patient that is being treated with fibrinolytics? (this pathway is not commonly used anymore)
Aspirin + clopidogrel
Why do we give a non-enteric coated chewable aspirin instead of another formulation of aspirin to patients presenting with ACS?
Chewed aspirin is more rapidly absorbed therefore its antiplatelet effects will occur more rapidly.
Why are loading doses of P2Y12 inhibitors not give to a patient experiencing a STEMI that is being treated with a fibrinolytic?
A loading dose of an antiplatelet would increase bleeding risk when used in combination with a fibrinolytic (clot buster). However, the loading dose for clopidogrel ranges from 300-600mg. In cases of a STEMI being treated with a fibrinolytic, a 300mg loading dose would be given but not the 600mg loading dose.
What is the loading and maintenance dosing for clopidogrel?
300mg LD (STEMI w/ fibrinolytic) or 600mg LD for everything not involving a fibrinolytic
75mg daily maintenance dose
What is the loading and maintenance dosing for prasugrel?
60mg LD
10mg maintenance dosing (5mg if weight is less than 60kg or age 75+)
What is the loading and maintenance dosing for ticegrelor?
180mg LD
90mg BID maintenance dosing
Technically speaking, the efficacy of ticagrelor is reduced when combined with aspirin doses of greater than 100 mg. So why is it okay to give aspirin and ticagrelor to a patient with ACS?
It is okay to give a few doses of aspirin (162-325mg) with ticagrelor but when using the medication longterm, aspirin doses do need to be reduced to under 100 mg daily.
When do we use glycoprotein IIb/IIIa inhibitors (tirofiban and eptifibatide) in cases of ACS?
They are not used unless administered in the actual cath lab or the cardiologist wants to administer it. It can be considered in patients with NSTEMI and high risk features like a large thrombus.
When are anticoagulants added into the mix for ACS?
Some NSTEMI patients may need anticoagulation therapy in addition to aspirin and a P2Y12. These 3 together are ONLY used before revascularization can occur in an NSTEMI patient.
What do the guidelines recommend for anticoagulation therapy in addition to aspirin and a P2Y12 inhibitor for patients that need it prior to revascularization in the cath lab?
The only recommended options for anticoagulation in cases of ACS only during a patient’s hospital stay are IV anticoagulants like unfractionated heparin, bivalarudin, and enoxaparin.
Which type of heparin has the shortest half life?
Unfractionated heparin (THE heparin)
If CABG revascularization is being performed for an NSTEMI, what anticoagulant in recommended on top of the aspirin and P2Y12 inhibitor?
Unfractionated heparin
If PCI revascularization is being performed for an NSTEMI, what anticoagulant in recommended on top of the aspirin and P2Y12 inhibitor?
Bivalarudin and enoxaparin
Fondaparinux can be used but if it is, it can’t be the only anticoagulant on board due to risk of catheter thrombosis during procedure.
Are oral or IV anticoagulants give to NSTEMI ACS hospital patients prior to revascularization?
IV only always for ACS events
What anticoagulants should NEVER EVER EVER been used in cases of ACCS?
Warfarin and DOACs!!!!!
What is the unfractionated heparin dosing prior to revascularization for NSTEMI hosptial patients?
Initial therapy includes a loading dose of 60 IU/kg (max 4000 IU) with initial infusion at 12IU/kg/hr (max 1000 IU/hr) adjusted for aPTT range of 60-80s.
What is the bivalarudin dosing prior to revascularization for NSTEMI hosptial patients?
0.75 mg/kg bolus followed by 1.75mg/kg/hr via IV infusion during PCI procedure.
What is the fondaparinux dosing prior to revascularization for NSTEMI hosptial patients?
2.5 mg SubQ daily
What is the enoxaparin dosing prior to revascularization for NSTEMI hosptial patients?
Initial therapy includes 1mg/kg SubQ every 12 hr.
(1mg/kg every 24 hr if CrCl less than 30)
Why is unfractionated heparin the preferred anticoagulant given prior to CABG revascularization?
Unfractionated heparin has the quickest on and off time allowing for less bleeding risk
Considering the medications given for a PCI following ACS, how do medications change when a patient undergoes a CABG instead?
The medication remain mostly the same (think unfractionated heparin as the anticoagulant of choice in CABG though), however the timing is different due to the major risk for bleeding in a CABG procedure.
T or F: Just as aspirin is given prior to a PCI in the cath lab (even if they take it at home and already took it for the day), the same thing is given to patients undergoing a CABG.
True. Just as patients would take a non-enteric coated aspirin before a PCI, patients will also take this before undergoing a CABG.
Explain P2Y12 administration timing for an elective CABG procedure.
If that patient is already on a P2Y12 inhibitors clopidogrel or ticagrelor, discontinue the regimen for a minimum of 5 days before surgery. If they were on prasugrel, discontinue the regimen for a minimum of 7 days before surgery.
Before an elective CABG, a patient already on clopidogrel needs to have that medication discontinued at least _______ days prior to surgery.
5 days
Before an elective CABG, a patient already on ticagrelor needs to have that medication discontinued at least _______ days prior to surgery.
5 days
Before an elective CABG, a patient already on prasugrel needs to have that medication discontinued at least _______ days prior to surgery.
7 days
Explain P2Y12 administration timing for an urgent CABG procedure.
If the patient is already on clopidogrel or ticagrelor, discontinue the medications for a minimum of 24 hours before the CABG procedure to reduce the risk of bleeding.
For example, if a PCI was being performed and the surgeons realized they needed to switch to a CABG but the patient is on a P2Y12, they would need to wait at least 24 hours to begin surgery after discontinuing the medication.
Explain glycoprotein IIb/IIIa administration timing for patients referred for a CABG procedure.
If a patient takes tirofiban or eptifibatide, these medications need to be discontinued for at least 2-4 hours prior to surgery. If the patient is on abciximab, it needs to be discontinued for at least 12 hours prior to surgery.
What is the typical presentation of a STEMI?
Unremitting chest pain
What happens the moment the diagnosis if officially a STEMI based on EKG readings?
The patient is going to the cath lab pretty much right away for urgent revascularization via PCI ASAP. If the hosptial does not have the resources, fibrinolytics can be given.
Per the guidelines, how soon should a STEMI patient be in the cath lab after presenting with their symptoms?
90 minutes following onset of symptoms.
Per the guidelines, how soon should the blocked coronary artery in a STEMI be reopened/ revascularized via a PCI?
3 hours following the onset of symptoms.
T or F: Fibrinolytic treatment for STEMI shows better outcomes compared to PCI treatment for a STEMI.
False. PCI treatment indicated lower mortality rate in comparison to fibrinolytics. PCIs open arteries better than fibrinolytics. Additionally, PCIs reduce the risk for major bleeding and an intracranial hemorrhage.
Do STEMI patients treated with fibrinolytics eventually get anticoagulants?
Full anticoagulation with unfractionated heparin or enoxaparin needs to be initiated following for at least 48 hours following but should likely last a maximum of 8 days.
T or F: If a cath lab is not available, fibrinolytics are indicated in both NSTEMI and STEMI.
False. Fibrinolytics are NEVER indicated in an NSTEMI. Fibrinolytics are only indicated in STEMI patients that meet certain criteria. Fibrinolytics are always contradinicated in patients with a high bleeding risk.
What are the two major side effects of fibrinolytics?
Intracranial hemorrhage and major bleeding
What is the criteria a STEMI patient must meet to qualify for fibrinolytic therapy?
- Must present within 12 hours of symptom onset
- STE elevation on EKG greater than 1mm
When are fibrinolytics contraindicated?
There are absolute and not absolute contraindications for fibrinolytic use. Absolute contraindications for fibrinolytic use include PMH of intracranial hemorrhage, cerebral vascular malformation, aortic dissection, active bleeding, recent intracranial or spinal surgery, on anticoagulants, active endocarditis, acute ischemic stroke in last 3 months, or head injury in the last 3 months.
Do STEMI patients treated with fibrinolytics eventually get any antiplatelets?
Clopidogrel 75mg should be used for at least 14 days following coronary reperfusion with fibrinolytics.
If a STEMI patient does qualify for fibrinolytic therapy, a drip of the medication needs to be started with ________ minutes of that patients arrival.
30 minutes
How long should STEMI patients managed with fibrinolytics be on full anticoagulation?
Minimum of 48 hours and a maximum of 8 days.
Oxygen therapy is required in NSTEMI patients if their O2 stats are below ________%.
90%
What is a serious contraindication for beta blocker use?
Severe bradycardia
What medication is first line to relieve chest pain in NSTEMI patients?
Nitroglycerin
T or F: Beta blockers are recommended for early treatment in NSTEMI.
True
T or F: Not all patients with NSTEMI get an ACE or an ARB.
True
T or F: Warfarin and DOACs are used in ACS events.
FALSE
List the 6 medications and doses for post-ACS discharge medications.
- Aspirin: 81mg BID
- P2Y12 Inhibitor: Ticagrelor (90mg BID) or Prasugrel (10mg) preferred
- Beta-blocker: metoprolol succinate, carvedilol, or bisoprolol
- ACE inhibitor: can use ARB is ACE intolerant
- High intensity statin:
- Nitroglycerin: Sublingual PRN for angina or ACS recurrence
In the default strategy post-ACS, how long is a patient on dual-antiplatelet therapy?
At least for more than 12 months. The aspirin is continued indefinitely but P2Y12 discontinuation can be considered after 1 year.
If a person has a very high bleeding risk following PCI intervention, how is anti-platelet therapy managed post-ACS?
- Dual-antiplatelet therapy with aspirin and P2Y12 for 1 month
- Stop aspirin or the P2Y12 after 1 month
- Continue one as monotherapy for at least 12 months
All ACS patients need to be sent home with a high-intensity statin. What is the post-ACS LDL goal and what medication is added is patients are not at that goal?
The LDL goal is less than 55. If there LDL is greater than 70 or between 55 and 69, add ezetimibe or PCSK9-I.
Obtain a lipid panel 4-8 weeks after initiation of the statin therapy.
A lipid panel should be conducted _____-_____ weeks after statin initiation in post-ACS patients.
4-8 weeks
What are the 4 things included in secondary prevention for ACS patients?
- Cardiac rehabilitation
- Physical activity (150 minutes per week)
- DASH or mediterranean diet
- Lifestyle changes: smoking cessation, BP control, diabetes control, lipid control
The ____________ __________ requirement increases when there is an increase in heart rate, contractility, arterial pressure, or ventricular volume.
Myocardial oxygen
What two things can precipitate angina in patients with stable plaques?
Physical activity and sympathetic discharge
What are the 6 risk factor for chronic coronary disease?
Smoking, poor diet, lack of exercise, high lipid levels, comorbidities like HTN and diabetes, and overweight.
In patients that are diagnosed with chronic coronary disease but have yet to have an ACS event, what medication is recommended to reduce risk for an ACS event?
Aspirin 81mg
What 4 medications are used to reduce ischemia and relieve angina symptoms in those with chronic coronary disease?
Nitrates, beta blockers, CCBs, and ranolazine.
These medication reduce myocardial oxygen demand
What is the MOA of nitrates like nitroglycerin?
- Vein and artery dilation in the heart reducing wall stress from reduced ventricular volume and pressure.
- Systemic dilation increases bloodflow to deep myocardial tissue.
- Dilates large and small coronary arteries to relief spasms.
What is the first-line therapy for anginal attack prevention?
Nitrates like nitroglycerin
What are the 3 reasons that nitrates are used in therapy for chronic coronary disease?
- Terminates acute anginal attack
- Prevents stress-induced attacks
- Long-term prevention of ACS events
Can tolerance develop with nitrate use?
Yes! There needs to be an 8 hour nitrate-free period to prevent tolerance to this medication.
What is the sublingual nitroglycerin dosing for at-home prophylaxis?
0.3-0.4 mg taken 5 minutes before an activity
What is the heart rate goal for patients with chronic coronary disease?
Less than 70 bpm (this is what the beta-blocker is for)
What is the first-line medication for chronic angina that requires daily maintenance therapy?
Beta blockers (could be in addition to the nitrate and/or CCBs)
What is the MOA of calcium channels blockers in regards to the heart?
Non-DHP CCBs like diltiazem and verapamil reduce heart rate, contractility, and afterload. All the DHP CCBs like nifedipine only reduce afterload.
What is the main adverse effect associated with non-DPH CCBs like diltiazem and verapamil?
Bradycardia
What are the two main adverse effects associated with DHP CCBs?
Ankle edema and transient reflex tachycardia
_______ ________ should be prescribed as initial therapy for relief of symptoms in patients with stable ischemic heart disease/ chronic coronary disease.
Beta blockers
When should calcium channels blockers with nitrates be used in patients with stable ischemic heart disease/ chronic coronary disease?
If they are contraindicated for beta blockers or caused severe side effects for that patient, the beta blocker is stopped and DPH CCB and nitrates are started. If the beta-blocker does not work as monotherapy, DPH CCBs can be added in addition to the beta-blocker.
When would ranolazine be used for stable ischemic heart disease/ chronic coronary disease?
It is reserved for patient who have no achieved adequate responses with other antianginal medications. However, it can be used in combination with beta blockers for symptom relief if beta blocker monotherapy is not successful. It can also be a substitute for the beta-blockers.
What is the MOA of ranolazine?
It reduces the Ca2+ overload in ischemic myocytes through selective inhibition of late Na+ current. It prolongs the QT interval. It does NOT affect heart rate, inotropic state, hemodynamic state, or increase coronary blood flow.
What is a precaution that needs to be noted when combining beta-blockers and non-DPH CCBs?
Higher risk for bradycardia
When choosing a calcium channel blocker for chronic coronary disease, are non-DPHs or DPHs preferred?
DPHs CCBs like amlodipine and nifedipine are preferred.
What is the dosing for Ranolazine?
500mg BID then 1000mg BID
What are the 2 contraindications for ranolazine use?
- Preexisting Qt interval prolongation
- Hepatic impairment
Chronic stable angina therapy is considered successful if the patients have a functional capacity of CCS class _____ angina.
Class 1
Define heart failure.
Heart failure is a progressive clinical syndrome that can result from any disorder that impairs the ability of the ventricle to fill with blood or eject blood. The heart is not able to pump blood at a rate that meets the metabolic demands of the body.
What is the most common cause of heart failure?
Coronary artery disease
What are the 5 risks factors that increase the likelihood of developing heart failure?
MI, HTN, diabetes, obesity, and smoking
What is ejection fraction of the heart?
Ejection fraction is the amount of blood the left ventricle pumps into the body in 1 heart beat.
What is the typical ejection fraction for a normal healthy heart?
Around 55%. This means that 45% of the blood stays in that ventricle.
What is the % ejection fraction that categorizes heart failure with reduced ejection fraction (HFrEF)?
40% or less
What are the 3 characteristics of heart failure with reduced ejection fraction?
- Decreased contractility
- LVEF 40% or less
- Increased left ventricle size
What is heart failure with preserved ejection fraction (HFpEF)?
LVEF is 50% or greater but the ventricles do not get an adequate amount of blood from the venous system and these patients have a difficult time maintaining stroke volume.
The ventricles do not fill as much for example it might fill with 8ml of blood and not 12ml in a normal person. If that heart can still eject 4ml of blood, then the ejection fraction is 50%. The heart is still failing, but in a different way in comparison to HFrEF.
What are the 4 compensatory mechanisms activated in the body in response to heart failure?
- RAAS activation
- Adrenergic system activation
- Increased myocardial contractility
- Vasodilatory mechanism activation (BNP, NO, and prostaglandins)
What is the first compensatory mechanism that is activated in response to heart failure?
Autonomic nervous system dysfunction/ adrenergic systemic activation
What is occurring when the autonomic nervous system begins to dysfunction in heart failure?
There is an increase in sympathetic tone and decrease in vagal tone causing increased heart rate even at rest to maintain cardiac output. Systemic vascular resistance also increases due to release of local vasopressors and structural changes to vessels.
What are the 4 favorable effects of autonomic nervous system dysfunction in severe heart failure?
Increased heart rate
Increased contractility
Improved cardiac output
Maintain perfusion pressure
These are typically not good in those without severe heart failure as it will lead to remodeling
What are the many unfavorable effect of autonomic nervous system dysfunction in heart failure?
- Left ventricle remodeling and hypertrophy
- Arrhythmias
- Increased systemic vascular resistance increasing afterload
- sodium and water retention
- Renin release
What is the second compensatory mechanism that is activated in heart failure following autonomic nervous system dysfunction?
RAAS activation
What are the negative effects of RAAS activation in heart failure?
Bad effects occur at the angiotensin II type I receptor
- arterial vasoconstriction
- cell hypertrophy
- apoptosis in myocytes
- polydipsia
- norepinephrine release
What compound causes hyponatremia in heart failure patients?
Arginine vasopressin
How does arginine vasopressin excessive release in heart failure contribute to hyponatremia in these patients?
Arginine vasopressin tells the kidneys to hold onto water and its actions can indirectly affect sodium levels. Excess AVP can lead to water retention, diluting the sodium concentration in the blood, resulting in hyponatremia.
What are the 3 natriuretic peptides?
ANP (Atrial Natriuretic Peptide), BNP (Brain Natriuretic Peptide), and CNP (C-type Natriuretic Peptide)
T or F: Natriuretic peptides are increased in heart failure and cause vasodilation and natriuresis.
True. BNP levels can be measured in heart failure.
What is natriuresis?
Excretion of sodium in the urine
___________ of the heart leads to cardiac failure.
Remodeling
What are the 6 factors that can worsen heart failure?
- non-compliance with therapy or diet
- cardiac events
- atrial fibrillation
- pulmonary infections
- anemia
- drugs (anti-arrhythmics, beta blocks, nonDHP CCBs, conazoles, ethanol, and more)
Long-term __________ use is directly cardiotoxic and can precipitate heart failure.
Ethanol
What classes of medications can precipitate heart failure?
- Negative inotropes- anti-arrhythmics, beta blockers, non-dhp CCBs, itraconazole, and terbenafine
- Directly cardiotoxic- ethanol and a bunch more
- Na+/H20 retention- NSAIDS, COX-2 inhibitors, hormones, steroids, etc
What categorizes a patient as NYHA class I (mild)?
No limitation in physical activity as in normal day-to-day activities do not cause fatigue, palpitations, SOB, etc.
What categorizes a patient as NYHA class II (mild)?
Slight limitation in physical activity as in these patients are comfortable at rest but day-to-day physical activity results in fatigue, palpations, and SOB.
What categorizes a patient as NYHA class III (moderate??
Marked limitation of physical activity meaning they are comfortable at rest but even less than ordinary activity like getting off the couch and brushing teeth causes fatigue, palpatations, SOB, etc.
What categorizes a patient as NYHA class IV (severe)?
Unable to carry out any physical activity without discomfort and there are symptoms of cardiac insufficiency at rest.
T or F: All NYHA functional classifications of heart failure fit into the AHA/ACC stage C or D of heart failure.
True. NYHA categorizes the symptoms of heart failure meaning these patients are at least mildly symptomatic. In AHA/ACC stages of heart failure, stage C is symptomatic heart failure so this makes sense.
What is classified as stage A heart failure per the AHA/ACC guidelines?
These are patients at-risk for heart failure but they have no symptoms or signs of heart failure. This could include patients with HTN, diabetes, obesity, genetic variants, cardiotoxic agents, family history, and more
What is classified as stage B heart failure per the AHA/ACC guidelines?
These are patients without current or previous signs and symptoms of heart failure but they have evidence of 1 of the following; structural heart disease, evidence of increased filling pressures, or risk factors with increased natriuretic peptide levels, or persistently elevated cardiac troponin levels.
What is classified as stage C heart failure per the AHA/ACC guidelines?
Patients with current or previous signs and symptoms of heart failure.
What is classified as stage D heart failure per the AHA/ACC guidelines?
Evident heart failure symptoms that interfere with daily life with recurrent hospitalization despite attempts to optimize medical therapy.
For patients with AHA/ACC stage A heart failure, what are the appropriate prevention measures?
In stage A patients, treatment starts at the level of treating risk factors. This means that if they have hypertension, an ACE or ARB would be added. Additionally lifestyle counseling is important here including smoking cessation and alcohol cessation.
What are the subjective symptoms of heart failure (what the patient is experiencing)?
Dyspnea (SOB)
Orthopnea (laying down SOB)
Paroxysmal nocturnal dyspnea (SOB while sleeping)
Fatigue
Exercise intolerance
Fluid overload (pulmonary and peripheral edema)
Hemoptysis (coughing up blood)
Abdominal pain
anorexia
Nausea
bloating
poor appetite
What are the objective signs of heart failure?
- Pulmonary rales and edema
- S3 gallop
- cool extremities
- pleural effusion
- Cheyne-stokes respiration
- tachycardia
- cardiomegaly
- jugular venous distention (JVD)
- hepatojugular reflux
- hepatomegaly
What labs are run to determine heart failure?
BNP and pro-BNP. If elevated, it indicates a greater risk for short and long term outcomes with heart failure. SCr may also be decreased so can measure that as well.
_______________ is a marker of reduced survival and heart failure progression.
Hyponatremia
What are the two ways in which ejection fraction is determined?
Echo and catheterization
Before any medications are given for heart failure, what things should be done?
Treat and remove any underlying etiology causing the heart failure if possible. It could entail a valve replacement or repair, revascularization or anti-ischemic therapy in patients with CAD, reverse atrial fibrillation, and/or remove any drugs aggravating the heart failure.
What are the 4 non-pharmacologic methods used in addition to medications in those with heart failure?
- sodium restriction (2-3 grams per day or less than 1.5g for HTN)
- water restriction (2L per day)
- daily weight measurement (fluid overload)
- exercise
Which compensatory mechanism is beneficial in heart failure?
Upregulation of natriuretic peptides because they cause vasodilation.
Which lab is likely to be elevated in heart failure due to the disease and not any medications?
BNP
What are the two goals of pharmaceutical treatment for heart failure?
- Reduce ventricular preload and afterload
- Diminish neurohormonal vasoconstrictor activation (block adrenergic activation and RAAS)
What are the 5 medications that 99.9% of heart failure patients will receive?
- diuretics (thiazide or loop)
- ACE/ARB/ARNI
- Beta blocker
- SGLT2
- Spironolactone or eplerenone
Why do heart failure patients need a thiazide or loop diuretic?
Fluid retention is very common in heart failure. These diuretics help heart failure patients maintain euvolemia.
_____________ produce symptomatic benefits the fastest in heart failure.
Diuretics
T or F: Diuretics decrease hospitalizations and mortality among heart failure patients.
False. Diuretics decrease hospitalizations but there is no data on long-term mortality outcomes.
What are the 4 symptomatic benefits of diuretics in heart failure patients?
- decrease fluid retention
- improve exercise tolerance
- improve quality of life
- decrease hospitilizations
Diuretics in heart failure reduce __________ but have little effect on stroke volume and cardiac output in heart failure patients.
Preload
Why must diuretics be used with caution in heart failure patients?
Overdiuresis can decrease cardiac output and lead to dehydration.
How are diuretics dosed in heart failure?
Low doses for outpatient heart failure patients and titrate dose based on water weight gain.
Which type of diuretic is preferred in heart failure?
Loop diuretics like furosemide, torsemide, or bumetanide. If a person does not respond to the loop, a thiazide can be added on with the loop.
How is it determined that someone is a non-responder to loop diuretics?
Fluid weight gain
How is IV furosemide (lasix) converted to PO furosemide?
PO:IV is 2:1
For example, if a patient is on 80 mg of PO lasix, they would be on 40 mg of IV lasix. The other loop diuretics like bumetanide and torsemide are 1:1.
What needs to be monitored when a patient is on loop diuretics?
Renal function and electrolyte status
Why are ACE inhibitors used in heart failure?
They inhibit left ventricular remodeling after a myocardial infarction.
T or F: ACE inhibitors and ARBs increase survival and decrease hospitalizations in heart failure patients.
True! They also increase quality of life.
What is the drug Entresto?
This is an ARNI medication that includes both an ARB (valsartan) and a neprilysin inhibitor (Sacibitril).
What is the MOA of neprilysin inhibitors?
They increase natriuretic peptide levels by stopping their breakdown. They degrade angiotensin II as well to stop activation of RAAS.
When is Entresto indicated in heart failure and not just an ACE or an ARB?
It reduces the risk for cardiovascular death and hospitalization for heart failure patients with heart failure NYHA class II, III, and IV and those with reduced ejection fraction.
T or F: All patients with HFrEF should be on an ACE inhibitor, ARB, or ARNI (Entresto).
True! ARNI is preferred if patient has access.
T or F: ACE inhibitor and ARB dosing have targets that should be reached in order to reduce mortality in heart failure patients.
True
What are the only 3 beta blockers that are used in heart failure?
Metoprolol succinate (XL), carvedilol, and bisoprolol
T or F: Beta blockers reduce mortality in heart failure patients but have no effect on hospitalization rates.
False. Beta blockers reduce mortality and hospitalization rates in those with heart failure. Beta blockers have little to no effect on exercise tolerance.
Beta blockers increase _____________ and symptoms of heart failure.
Increases LVEF and improves symptoms and clinical status after about 3 months on the medication.
Why does it take around 3 months to see symptom and clinical status improvement in heart failure patients on beta blockers?
Initially, beta blockers can worsen heart failure by reducing ejection fraction but once the beta blocker is titrated up to the correct heart failure dosing, symptoms should improve.
How are beta-blockers titrated up to their appropriate dose?
Double the dose every 2 weeks until the target dose is reached.
What is the initial metoprolol succinate (Toprol XL) dosing for heart failure NYHA class II?
25 mg QD
What is the initial metoprolol succinate (Toprol XL) dosing for heart failure NYHA class III and IV?
12.5 mg QD
What is the target metoprolol succinate (Toprol XL) dosing for heart failure patients of all NYHA classes?
200mg daily
What is the initial carvedilol dosing for heart failure?
3.125 mg BID
What is the target carvedilol dosing for heart failure for those weighing less than 85kg?
25mg BID
What is the target carvedilol dosing for heart failure for those weighing more than 85kg?
50 mg BID
What is the initial bisoprolol dosing for heart failure?
1.25mg daily
What is the target bisoprolol dosing for heart failure?
10 mg daily
What is the heart rate goal in heart failure?
50-60 bpm
T or F: Loop diuretics are superior for removing excess fluid whole thiazide diuretics are better for treating high blood pressure.
True
Why do the guidelines strive for providers to get patients with heart failure to the target doses for ACEi/ARBs/ARNIs?
The target dose for these medications has the best reduction in overall mortaility.
T or F: ACE inhibitors and ARBs should be combined in heart failure patients.
False. Never combine ACEs and ARBs.
T or F: Aldosterone increases are correlated with decreased left ventricle mass.
False. There are directly correlated meaning as aldosterone levels rise so does the mass of the left ventricle. This is why 99.9% of patients need to be on an aldosterone antagonist.
How does aldosterone play a role in heart failure?
Aldosterone increases sodium concentrations potentiating edema, increase LV mass and fibrosis potentiating remodeling, decreases potassium and magnesium potentiating arrhythmias, and increases ischemic events.
When it the only case scenario in which aldosterone antagonist like spironolactone or eperlenone are not given?
SCr greater than 2.5 mg/dL
In order for a patient to get an aldosterone antagonist in heart failure, the patients needs to meet what 2 requirements?
GFR > 30 mL/min and serum K+ < 5 mEg/L
What are SGLT2 inhibitors?
These are sodium-glucose cotransporters. By inhibiting this transporter, the reabsorption of glucose is decreased and more is excreted as well as water.
Why are SGLT2 inhibitors used in heart failure?
The MOA of benefit in heart failure is unknown.
What are the adverse effects associated with SGLT2 inhibitors?
Hypotension
Hyperkalemia
Genital mycotic infections
UTIs
Increased urination
Euglycemic DKA
AKI
Bladder cancer
amputations
pancreatitis
What 5 populations are contraindicated for SGLT2 inhibitors?
Type 1 diabetics, allergies, severe renal impairment, end-stage renal disease, and those on dialysis.
What are the 2 SGLT2 inhibitors approved for use in heart failure?
Dapaglafozin and Empaglaflozin
When are SGLT2 inhibitors indicated in heart failure?
They are used in HFrEF.
T or F: SGLT2 inhibitors reduce the rate of hospitalizations and deaths in heart failure patients.
True
What are the 6 medications that only certain populations of those with heart failure will recieve?
- Long acting nitrates with hydralazine
- Ivabradine
- Digoxin
- Vericiguat
- Omega 3s
- potassium binders
When would long-acting nitrates and hydralazine be given in heart failure?
- If the patient is african american with NYHA class III or IV heart failure
OR - other patients who are intolerant to ACE/ARB/ARNI
T or F: Long acting nitrate and hydralazine combination are show to only reduce mortality.
True. These have no affect on hospitalization rates.
What are HCN channel blockers?
HCN channels blockers block the hyperpolarization-activated cyclic nueleotide-gated channels. The functions to lower heart rate.
What is the one HCN blocker learned in this section?
Ivabradine
When is ivabradine indicated in heart failure?
- LVEF 35% or less in sinus rhythm
- HR 70 BPM or greater
- on maximally tolerated dose of beta blocker or have contraindication
What is the dosing for ivabradine?
5 mg PO BID. Adjust dose based on HR and tolerability, do not exceed 7.5mg BID.
What effect does the HCN channel blocker, Ivabradine, have on mortality and hospitalizations?
No changes to mortality and may have a small decrease in hospitalizations.
What type of drug is Vericiguat?
This is an sGC activator that binds sGC and enhances the effect of nitric oxide to increase cGMP activity.
What effect does Vericiguat have on mortality and hosptilizations?
Combined decreased in death and hospitalizations
What is the dosing for VEriciguat?
2.5 mg daily. Max is 10mg daily
What effect does digoxin have on morality and hospitalizations in heart failure?
No effect on mortality but reduces rates of hosptial admissions.
What is the indication for use of digoxin in heart failure?
For those with symptomatic HFrEF even on guidelines directed therapy for heart failure.
What effect do omega-3 fatty acids have on mortality and hospitalizations in heart failure?
They reduce mortality and hospitalizations.
What are the two potassium binding agents that may be used in HFeRF?
Patiromer or Sodium Zirconium Cycosilicate. These are only indicated for patients on ACE/ARB/ARNI but have a potassium above 5.5 mEq/L.
In pregnant people with heart failure, what agents should absoluetly not be used?
ACE
ARB
ARNI
Aldosterone antagonist
SGLT2
Ivabradine
Vericiguat
What heart failure medications are safe in pregnancy?
Metoprolol succinate, hydralazine, nitrates, and diuretics
T or F: Ivabradine reduces mortality rate in patients with heart failure.
False. It may have some small decreases in hospitalizations.
What is the BP goal for those with HFpEF?
Less than 130/80
When are SGLT2 inhibitors used in HFpEF?
- NYHA class II-IV
- BNP greater than 100
if yes, they are used in combo with spironlactone
What is acute heart failure/decompensated heart failure?
It is a relatively sudden inability of the heart to maintain cardiac output adequate for the demands of the body.
What causes acute heart failure/ decompensated heart failure?
This type of heart failure is in response to neuroendocrine activation. It include sympathetic activation, RAAS activation, cytokine and endothelin release, and peptide release of vasopressin and natriuretic peptides.
What are the many things that can cause acute/decompensated heart failure?
- non-adherence with medical regimen
- acute myocardial ischemia
- uncorrected BP
- A fib or other arrhythmia
- addition of negative inotropic drugs
- PE
- NSAIDS
- alcohol and illicit drugs
- endocrine abnormalities
- infections
What is the TX approach for acute decompensated HF?
IV diuretics
IV vasodilators
IV positive inotropes
Which of the following is NOT a compensatory mechanism for heart failure?
A. Vasodilation due to increased NO, BNP, and prostaglandins
B. Activation of RAAS
C. Cardiac remodeling
D. Increased myocardial contracility
C. Cardiac remodeling
Which of the following is not a subjective sign of heart failure? (Subjective is what the patient is experiencing)
A. HTN
B. Orthopnea
C. Exercise intolerance
D. Fluid overload
E. Poor appetite
A. Hypertension
Which of the following lab values may be consistent in a patient with heart failure?
A. BNP >100
B. Elevated SCr
C. Hyponatremia
D. All of the above
D. All of the above
When is hydralazine indicated in heart failure patients?
A. African american patients with at least 3 months of LVEF <35%
B. African american patients with edema not controlled by loop diuretics
C. African american patients with potassium less than 5 and crcl less than 30
D. All of the above
A. African american patients with at least 3 months of LVEF <35%
Which of the following agents have mortality data in heart failure?
A. Furosemide
B. Entresto
C. Digoxin
D. Beta blockers
E. Aldosterone antagonist
F. Hydralazine and isosorbide dinitrate
G. Vericiguat
H. SGLT-2 inhibitors
I. Omega-3s
Entresto, Beta blockers, aldosterone antagonists, hydralazine and isosorbide dinitrate, and SGLT2
Loops only decrease hospitilizations
Which of the following explains the MOA of IV diuretics in acute decompensated heart failure?
A. Decreased preload
B. Decreased afterload
A. decreased preload
In patients with HFpEF, which of the following treatments is most recommended to reduce hospitalizations?
A. Loop diuretics
B. SGLT-2 inhibitors
C. Digoxin
D. Vericiguat
B. SGLT2 inhibitors
A patient with heart failure and persistent volume overload despite a loop diuretic, may benefit from the addition of what?
A. Thiazide diuretic
B. Beta blocker
C. Digoxin
D. SGLT2 inhibitor
A. thiazide diuretic
