Exam II Flashcards
(180 cards)
1
Q
Myocardial ischemia: Reperfusion injury can occur when introducing new blood during an MI.
Common manifestations of Reperfusion injury include:
- Myocardial stunning
- Microvascular dysfunction
- Lethal reperfusion injury
_________ occurs when there is myocyte injury and death. It is associated with contraction band necrosis (myofibril contraction + reperfusion induced Ca2+ injury)
A
Lethal Reperfusion Injury
2
Q
Heart Failure drugs:
- Thiazides and Thiazide-like diuretics inhibit the ________ cotransporter in the DCT. This ultimately decreases Na reabsorption (inc. exretion of Na and water)
- They also increase expression of _____ calcium channels (increasing Ca2+ absorption and subsequent transport to the interstitium via NCX1)
A
- Na/Cl- (NCC)
- TRPV5
- -hypercalcemia
3
Q
Heart failure drugs: Diuretics help to decrease the volume overload in HF (dec. congestive symptoms). They are also used in HTN and edema.
What are the effects of diuretics in HF?
A
- Loop diuretics (furosemide)
- -higher efficacy in HF - Thiazide-like diuretics (metolazone, chlortalidone)
- -more potent than thiazides (hydrochlorothiazide)
- -longer duration w/ fewer side effects
- -good at night - K+ sparing diuretics (spironolactone)
- -less useful in acute decompensated HF
NOTE: Do NOT improve mortality or morbidity
NOTE 2: Thiazides and K+ sparing often combined w/ Loop
4
Q
Angina drugs - Ca2+ channel blockers:
_____ (amlodipine, felodipine) decrease arteriolar tone and systemic vascular resistance (TPR). This helps to decrease arterial and intraventricular pressure.
- dec. wall tension
- dec. O2 demand
A
Dihidropyridines
amlodipine, felodipine
5
Q
Endocarditis: Infective endocarditis is classified in several ways:
- Temporal evolution
- Infection site
- Cause of Infection/Pre-disposing risk factor
True/False - With regard to the cause of infection, Intravenous drug abuse (IVDA), prosthetic heart valves and congenital abnormalities may be involved.
A
True
6
Q
Myocarditis: When would you suspect viral myocarditis?
A
Px presents w/ recent febrile illness, prominent myalgia followed by angina-like chest pain, dyspnea or arrhythmia.
Dx: Elevated troponin
Initial Injury: 2ndary to direct invasion by the virus
NOTE: further injury w/ IL-1, TNF, anti-heart Abs
7
Q
Heart failure drugs: Diuretics help to decrease the volume overload in HF (dec. congestive symptoms). They are also used in HTN and edema.
What are the effects of diuretics in HF?
A
- Loop diuretics (furosemide)
- -higher efficacy in HF - Thiazide-like diuretics (metolazone, chlortalidone)
- -more potent than thiazides (hydrochlorothiazide)
- -longer duration w/ fewer side effects
- -good at night - K+ sparing diuretics (spironolactone)
- -less useful in acute decompensated HF
NOTE: Do NOT improve mortality or morbidity
NOTE 2: Thiazides and K+ sparing often combined w/ Loop
8
Q
These K+ sparing diuretics induce
- hyperkalemia
- metabolic acidosis
A
Amiloride/Triamterene (non-steroidal)
Amiloride: 1st pass
9
Q
Heart Failure: The following describes heart failure on what side?
- dyspnea (difficulty w/ inspiration)
- bibasilar inpiratory crackles
- -“cardiac asthma”
- rust-colored sputum (heart-failure cells)
- pulmonary edema
A
Left sided heart failure
- juxtacapillary J receptors - rapid shallow breathing
- fluid collects around bronchioles – expiratory wheezing “cardiac asthma”
10
Q
Endocarditis: Remember, infective endocarditis usually affects L. side of heart (mitral). If the right side is involved, IV drug abuse.
The most common cause is bacteremia (infection). Patients often present with a fever of unknown origin***.
What are the most common infective species and ways to diagnose?
A
- S. aureus (MC)
- -high virulence
- -previously damaged or normal - Strep Viridans (2nd MC)
- -low virulence
- -infect previously damaged valve
Diagnosis:
- -blood culture
- -Echo
- -fever (unknown origin)
- -heart failure MC cause of death
11
Q
Myocarditis: Chagas Disease: In acute Chagas disease, cardiac damage results from direct invasion of myocardial cells and subsequent inflammation. It is mild in most, but can lead to progressive cardiac failure. How is it diagnosed?
A
Dx: find organisms in blood
NOTE: Following acute phase, many become asymptomatic, which can last lifetime
12
Q
Anti-arrhythmics: True/False - Flecainiade (Class IC) can be used during pregnancy and is a first line choice for fetal SVT
A
True
13
Q
Endocarditis: Libman-Sacks and Non-bacterial thrombotic endocarditis are non-infectious vegetations, meaning they did not occur from bacterial or viral infection.
Describe these forms of endocarditis, how they arise, and what they affect
A
- Libman Sacks
- sterile, warty lesions
- systemic lupus
- lesions: either side of valve
- Tri and Mi valves
* deformity - Non-bacterial thrombotic
- non-deforming sterile veg.
- platelets and fibrin
- due to procoagulant circulating mucin (pancreatic/colon cancer)
* *embolize w/ infarct
14
Q
Heart failure drugs: PDE inhibitors are contraindicated with which of the following drugs?
a. digitalis
b. heparin
c. warfarin
d. insulin
e. tizanidine
A
Answer: Tizanidine (muscle relaxant)
Also: Selegiline (MAO inh.); Anagrelide (thrombocytosis)
—dec. b.p. and inc. side effects
15
Q
Myocardial Ischemia: True/False Over the ensuing weeks to months, infarcted tissue is replaced by dense scar tissue (type I). This tissue is not able to contract.
It can be stained with Trichrome stain.
A
True
16
Q
Heart Failure drugs: B1 blockers not only can be used to treat HTN, but can also be used to treat HF.
What are the actions of B-blockers on the heart? in blood vessels?
A
- Heart:
- -competitive antagonists of B1-receptors (sympathetic)
- slow heart rate and force of contraction (dec. b.p., dec. SA node)
-blocks NE/E
- Blood vessels:
- inc. dilation
- dec. b.p.
17
Q
Angina drugs: True/False: O2 requirements inc. where there is an increase in HR, contractility, arterial pressure or ventricular volume
A
True
NOTE: cardiac muscle cannot develop appreciable O2 debt during stress and repay it later
18
Q
Rheumatic fever: Diagnosis of a patient with rheumatic fever usually as follows:
“Patient presents with known group A strep pharyngitis followed 2-3 weeks by one or more of the other manifestations”
What is the criteria for diagnosis?
A
Need 2 major OR 1 major/2 minor criteria
Minor:
- -fever
- -arthralgia
- -raised erythrocyte sedimentation (ESR)
- -C-reactive protein
- -Leukocytosis
- -ECG w/ prolonged PR
- -previous episode of RF
19
Q
Myocardial Ischemia: Describe the pathologic finding during acute MI 3-7 days post-MI
A
Gross:
–Red (hemorrhage - necrotic area; granulation tissue)
Microscopic:
- -macrophages remove necrotic debris
- -Risk of rupture:
- —free wall: cardiac tamponade
- —mitral regurgitation (papillary muscles rupture)
- —interventricular septum (VSD – L to R shunt)
20
Q
Myocardial Ischemia: Atherosclerosis is the major cause of Myocardial Ischemia.
What again are the risk factors for atheroslerosis?
A
-Age (male >45; female >55)
-Family history of premature CHD
(1st degree male relative <55 or female <65)
-Lipid abnormalities (inc. LDL)
-Smoking ***
-HTN
-Diabetes mellitus
-elevated serum homocysteine levels
-metabolic syndrome (3x inc. risk for coronary atherosclerosis; 3/5 Dx)
NOTE: HDL >60 = reduced risk
21
Q
Angina drugs - Nitrates and Nitrites: In unstable angina, these drugs dilate _______ coronary arteries and thus reduce myocardial O2 demand.
A
dilate epicardial coronary arteries
*can also prevent platelet aggregation
22
Q
Myocardial Ischemia: Prinzmetal angina also known as _________ is pain associated with myocardial ischemia. It is caused by focal or diffuse spasm of the SM of a coronary artery.
A
Vasospastic angina
- hyperreactivity of vascular SM
- can involve normal or atherosclerotic vessels
23
Q
Myocardial Ischemia: True/False - During an MI, necrosis involves half of the thickness of the myocardium within 2-3 hours of onset. Usually, by 6 hours, ischemia is transmural.
A
True
24
Q
Heart Failure Drugs: Thiazides can induce vasodilation via activation of Ca2+ induced _____ channels. This hyperpolarizes the membrane, closing L-type Ca2+ channels and causes SM relaxation (vasodilation)
A
K+ channels
- hyperpolarize
- dec. Ca2+ release
- vasodilation
25
Describe the steps for managing atrial flutter/fibrillation and paroxysmal supraventricular tachycardia
1. Carotid sinus massage/valsalva
- -if hemodynamically stable
2-4. Drugs to slow ventric. rate
a. beta blockers, Ca2+ blockers, digoxin, adenosine
2-4. drugs to convert atrial rhythm
--ibutilide, dofetilide, sotalol
3-4. cardioversion if drugs don't work (plus aspirin)
--or as 1st choice
5. Long term management**** FOR EXAM
6. Catheter/surgical oblation or pacemaker
26
Anti-arrhythmics: Afterdepolarizations are believed to result from abnormal calcium influx during or immediately after phase ______ of ventricular action potential. They can lead to extrasystoles and tachycardia.
1. Early afterdepolarizations (EAD's) are often _____ induced which is why it can be a dangerous trigger for arrhythmia
2. Late or delayed (DAD's) are often ____ induced, which is why tachycardia can trigger an arrhytmia.
1. EAD: bradycardia induced
| 2. DAD: tachycardia induced
27
Heart Failure Drugs: Thiazides can induce vasodilation via activation of Ca2+ induced _____ channels. This hyperpolarizes the membrane, closing L-type Ca2+ channels and causes SM relaxation (vasodilation)
K+ channels
- hyperpolarize
- dec. Ca2+ release
- vasodilation
28
Ischemic Heart: Myocardial Ischemia (ischemic heart disease) is the leading cause of death in the U.S.
It results from an imbalance between myocardial O2 supply and cardiac demand. Atherosclerosis of the coronary arteries (coronary heart disease) can cause decreased perfusion to the heart, and thus, cause cardiac myocytes to be deprived of adequate O2 supply.
What are clinical presentations of Ischemic heart disease (coronary heart disease/myocardial ischemia)?
1. Angina pectoris
- -most common
- chest "pain" from ischemia tissue injury
* *inc. risk of infarction
* *discomfort, heaviness, rubber band, elephant
2. MI
- -ischemic necrosis of heart muscle
* heart attack
3. Chronic ischemia
- -results in heart failure
- -need O2 for contraction; not getting it
4. Sudden cardiac death
29
A 59 year old female presents to the clinic with syncope, angina and dyspnea. Upon auscultation, you can hear a crescendo-decrescendo that radiates to the carotids.
What is the most likely valvular disorder?
aortic stenosis
* commissural fusion
* calcified valve (hydroxyapetite)
* schistocytes (fragmented RBC's)
30
Myocardial Ischemia: Thrombosis of the RCA can lead to this.
Common features include:
- bradycardia (right. coronary supplies AV, SA)
- hypotension
- Rt. heart failure
- preserved LV function
RIght ventricular MI
31
The following describes what valvular disorder?
- opening snap
- history rheymatic fever
mitral stenosis
32
Heart Failure Drugs: What are common side effects of Thiazides?
Common:
1. Most common:
- headaches, blurred vision
- postural hypotension
- allergies (sulfonamide)
2. Others:
A. electrolyte imbalance (hypokalemia; metabolic alkalosis; hypercalcemia; hyponatremia; prolonged use)
B. metabolic imbalance
(dec. insulin = insulin tolerance; hyperuricemia = gout)
33
Heart Failure drugs: Phosphodiesterase inhibitors include amrinone and milrinone.
They are positive inotropes and are considered 2nd line agents for CHF.
When are they most used?
- IV
- short term management of acute HF and refractory HF
*milrinone higher activity than amrinone
34
The following describes what valvular disorder?
- holocystolic
- history of rheumatic fever
- radiates to axilla
Mitral regurg.
35
Myocardial Ischemia: Angina results from ischemia (loss of blood flow to the heart).
Ischemia leads to acidosis and decreased ATP formation. This loss of ATP impairs Na/K+ pumps, and leads to cell swelling and release of chemical mediators (adenosine) that stimulate pain receptors.
Where can the pain be felt?
* chest, neck, lower jaw, down left arm
| * Referred pain -- dermatomes that correspond to same segments as the heart (C7-T4 sympathetic afferents)
36
Herat failure drugs: B-adrenergic agonists are sympathomimetic drugs that stimulate the sympathetic nervous system.
What are examples of these drugs and their features?
1. Dopamine
- -non-specific
- -D1 = D2 > B > a
- -vasodilation
2. Dobutamine
- -selective
- B1 > B2 >> a
- -increases renal perfusion
* extremely strong (IV)
* not 1st line meds
* mainly in life threatening situations (acute HF; refractory HF; severe failure following MI, cardiogenic shock)
37
Heart Failure Drugs: WHat are the most common side effects of ACE inhibitors?
- dizziness, hypOtension
- dry cough***
- skin rashes
- fever
- hyperkalemia
NOTE:
- -Fetal toxicity (2nd-3rd trimester)
- -angioedema (rare)
- -acute renal failure
**NO CNS effects (No BBB)
38
Angina drugs: True/False: O2 requirements inc. where there is an increase in HR, contractility, arterial pressure or ventricular volume
True
39
Myocardial Ischemia: STEMI involves ST segment elevation and new Q wave formation.
Common complications of STEMI include
1. Cardiogenic Shock
2. Lethal arrhythmias
3. Heart Failure
4. Rupture
5. Mural thrombus
6. Pericarditis
Rupture usually occurs between days 3-7 (wall is the weakest). There are 3 possibilities:
a. Anterior wall rupture
b. Posteriomedial papillary muscle rupture
c. Interventricular septum rupture
Describe these
4. Rupture (days 3-7 (weakened wall))
a. ant. wall rupture (MC)
- -thrombosis of LAD, cardiac tamponade
- -rapid/fatal
b. posteromedial papillary muscle dysfunction
- -due to inferior MI (thrombosis of rt. coronary artery)
- -acute onset of mitral regurg./LHG
c. Interventricular septim rupture
- -thombosis of LAD
- -Left to R. shunt (RHF)
- -inc. O2 in RV
40
Heart Failure: Most ACE inhibitors are pro-drugs that must be activated.
Which of the following is not a pro-drug?
a. Captopril
b. Benazepril
c. Lisinopril
d. Quinapril
Answer:
Captopril (short acting)
Benazapril (intermediate)
Lisinopril (long acting)
41
Myocardial Ischemia: Chest discomfort described as pressure, heaviness, squeezing. It is typically diffuse, with gradual onset and offset after 2-5 minutes.
It is the most common clinical manifestation of myocardial ischemia.
Angina pectoris
*other symptoms: nausea, fatigue, diaphoresis, SOB
NOTE: usually middle aged males; females w/ menopause
Tx: Nitroglycerin (venodilation)
42
Rheumatic Fever: RF is a multi-system disease that occurs from an autoimmune reaction against ______. This affects multiple organ systems including joints, heart, skin and brain.
Nearly all manifestations resolve, EXCEPT valbular heart damage (chornic rheumatic heart disease)
Group A strep
43
Myocardial Ischemia:
1. What would we see in a patient who has >70% of the vascular cross sectional area?
2. What would we see in a patient who has 90% stenosis?
1. Asymptomatic at rest; Chest discomfort (Angina) w/ activity (mowing, shoveling snow)
2. Ischemia even at rest
- -chronically ischemic
44
Anti-arrhythmics: List the anti-arrythmic drugs associated with the classes listed:
```
Class I
Class II
Class III
Class IV
Other
```
Class I: Na2+ channel blockers
Class II: B- blockers
Class III: K+ channel blockers
--prolong effective refractory period (prolong action potential)
Class IV: Ca2+ channel blockers
Others: digoxin, adenosine and Mg Sulfate
45
Heart Failure: A form of heart failure that is normally due to a non-compliant (stiff ventricle).
Ejection fraction is normal at rest (dec. SV and LVEDV), but is decreased with exertion.
Diastolic Heart Failure
(HFpEF)
-S4 heart sound (secondary to blood enterning non-compliant ventricle)
Causes:
- LVH
- Hypertrophic cardiomyopathy
- Restrictive cardio (amyloidosis)
46
Myocardial Ischemia: A form of tissue death associated with rupture of atheromatous plaque within a coronary artery.
- thrombogenic necrotic material within the plaque is exposed
- platelets adhere to exposed material
- thrombus forms, occluding blood flow
* *ischemic necrosis of cardiac myocytes
Myocardial infarction
*ischemic necrosis of cardiac myocytes (due to plaque rupture in coronary artery)
Tx: Aspirin prevents further thrombosis (inhibits COX-1 which inhibits Thromboxane A-2)
47
Anti-arrhythmics: These class IV drugs are non-Dihydropyridine Calcium channel blockers.
They block Ca2+ channels in the heart and vascular SM. They are used to Tx supraventricular tachycardia.
Verapamil and Diltiazam
NOTE: Verapamil preferred during pregnancy
48
Rheumatic heart disease: _________ refers to the long term sequelae of acute RF (rheumatic fever). Over decades, patients commonly develop calcification and fibrosis of heart valves (esp. the mitral valve) leading to stenosis w/ resistance to flow.
Over time, inc. LA pressure leads to dilatation of the LA (inc. risk of atrial fibrillation)
Chronic rheumatic heart disease
- inc. fibrosis of leaflets (commissural fusion)
- inc. LA pressure and dilatation (atrial fib risk)
- pulmonary HTN
- leads to RVH (risk eventual R. sided HF)
49
Angina drugs: Ranolazine is a last choice drug for angina.
It works by inhibiting ____ influx in the heart, leading to reduced Na/Ca exchange and dec. calcium overload.
Ranolazine
*slight reduce in O2 demand
50
The following describes what valvular disorder?
- holosystolic
- IVDA
Tricuspid regurg.
51
Heart failure drugs: What are the adverse effects of Beta blockers?
- bradycardia
- hypOtension
- SOB
- drowsiness, depression
- Reynaud's (numb cold)
- sexual dysfunction
- bronchospasm (non-selective)
**Glucagon (Tx B-blocker overdose)
52
Anti-arrhythmics: This drug blocks the Na/K pump current -
- positive inotropic effect
- -negative chronotropic effect (not causing bradycardia).
It CAN be used during pregnancy.
Digoxin
53
Myocardial Ischemia: Sudden onset of severe, crushing retrosternal discomfort that lasts > 30 minutes.
It is NOT relieved by Nitroglycerin and can have radiating pain down the inner left arm, into the jaw, shoulder and epigastrium.
Acute MI
* referred pain C7-T4 sympathetics/dermatomes
* diaphoresis, anxiety, hypotension
54
Anti-arrhythmic drugs: True/False: Most anti-arrhythmic drugs are pro-arrhythmic
True
55
Myocardial Ischemia: Myocardial Oxygen supply is determined by two main factors:
1. blood flow through coronary arteries
2. oxygen carrying capacity
What affects oxygen carrying capacity?
1. Severe anemia
- -dec. cell count = dec. O2
2. Decreased O2 saturation
- -Hb issues (CO poisoning; Methemoglobinemia)
56
Anti-arrhythmics: This Class III drug is:
- given intravenously (IV)
- converts patients with atrial flutter or fibrillation to a normal sinus rhythm.
- inc. risk of patient harm (if error)
Ibutilide
NOTE: can cause torsade de pointes
**heightened risk of significant patient harm (if used in error)
57
Heart Failure: True/False - The type of heart failure (systolic or diastolic) can be determined by ejection fraction
True
1. low EF (<0.5) = systolic
2. normal EF (>0.5) = diastolic
NOTE:
- systolic: impaired contraction/ejection
- diastolic: impaired relaxation/filling
58
Anti-arrythmic drugs: Class IA anti-arrhythmic drugs are used when other Tx do not work. These act as open channel blockers (inc. QRS depolarization) and include the drugs:
- Disopyramide
- Procainamide
- Quinidine
1. Disopyramide
- -not used much
- -6hrs
2. Procainamide
- -IM and IV only in U.S
- -3rd level choice
- -lasts 7hrs; cleared in 6
3. Quinidine
- -life threatening arrhytmias
- -not used often
59
Heart failure: True/False - Left sided abnormal heart sounds/murmurs do NOT increase with inspiration, but intensity of R. sided murmurs DO increase on inspiration
True
Rinspiration
Lexpiration
60
Heart failure drugs: List the drug interactions with dobutamine
1. Monoamine oxidase inhibitors (anti-depressant)
- -inc. catechols
- -inc. dobutamine side effects
* dec. dose of dobutamine
NOTE: no interaction with CV drugs
61
Anti-arrhythmics: True/False - Class IV drugs slow the AV node conduction velocity and prolong the AV node refractory period. Thus, they terminate AV node re-entry that causes supraventricular tachycardia
True
62
Myocardial Ischemia: What is the most common trigger for plaque rupture w/ regard to acute coronary syndrome, angina and MI? What determines onset?
Trigger: sympathetic nervous system
--HR and BP
(physcial/sexual activity, anger, anxiety, work stress, cocaine, war/terror)
Onset: circadian rhythm of biological pathways
**MI's most common in the morning
NOTE: vulnerability of plaques to rupture (content of lipids and inflamm cells) is the MOST important
63
Angina drugs: Which of the following is a method for modifying risk factors for coronary atherosclerosis?
a. smoking cessation
b. reduce obesity
c. diabetes management
d. reduce HTN
e. reduce hyperlipidemia
f. gradual intro to exercise
All of the above
64
Heart Failure drugs: What are the 4 stages of Heart failure?
1. Stage 1
- -breathlessness/tiredness
- -brisk walk or jog (exertion)
2. Stage 2
- -comfortable when resting
- -heart races/breathlessness when walking or taking stairs
3. Stage 3
- -palpitation or tiredness
- -difficulty with simple tasks (getting out of a chair)
Stage 4
- -heart and breath inc. at rest
- -tiredness at rest
- -anxiety and palpations all the time
65
Anti-arrhythmics - Class C drugs: Flecainide can induce bronchospasm and seizures while Propafenone causes agrnulocytosis and anemia.
When are Class IC drugs most commonly used?
Severe supraventricular arrhythmias and/or life threatening ventricular arrhythmia
NOTE: PVC's in otherwise normal hearts should NOT be given flecainide
(perfectly controlled rhythm and rate leads to increased mortality and morbidity)
66
Anti-arrhythmics: Re-entry is characterized by retrograde conduction of an impulse into previously depolarized tissue. It is normally caused by a unidirectional conduction block in a bifurcating conduction pathway.
What are the 3 necessary requirements/events for re-entry to occur?
1. obstacle to normal AP conduction
2. unidirectional block (dec. conduction of the impulse anterograde; normal conduction retrograde)
3. conduction time through the retrograde pathway MUST exceed the refractory period of the re-entered tissue
67
Heart Failure: What are the most common side effects of vasodilators?
- headache, nausea, diarrhea, flushing, hypotension
- tachycardia (due to hypotension)
- inc. RAAS
* countered by B-blockers and diuretics
NOTE: prolonged use of hydralazine at high doses = lupus like syndrome
NOTE 2: Nesiritide can induce renal failure; inc. risk of mortality; no arrhythmias
68
Endocarditis: Infective endocarditis is usually caused by bacterial infection of the endocardial surface of the heart.
It primarily affects the cardiac valves and sometimes involves the mural endocardium. What is the mechanism by which it damages the valves?
1. Fibrin/platelets adhere to valve
- -damaged area -- forms clot
2. Bacteremia leads to infection of clot
3. Organisms within clot proliferate
- -vegetation (friable - break off and form emboli)
4. Infection and subsequent host immune response damages valve leaflets
- -or chordae tendinae
- -heart murmur
69
Angina drugs:
What drugs serve as the drug of choice for treating variant (vasospastic) form of angina
Calcium Channel blockers
--- relieve and prevent coronary artery spasm, increasing coronary blood flow.
NOTE: nifedipine/nimodipine = inc. reflex tachycardia
70
Myocardial Ischemia: Because the myocardium cannot increase O2 extraction, an increase in O2 demand requires increased perfusion (blood flow).
Which of the following are determinants of oxygen demand?
a. HR
b. myocardial contractility
c. myocardial wall tension
d. systolic b.p. (afterload)
All of the above
* Wall tension:
- -product of preload and myocardial muscle mass
- -inc. tension = inc. O2 demand
*Also: physical activity, thryotoxicosis (e.g. hypothyroidism), aortic stenosis, cocaine/amphetamines inc. O2 demand
71
Heart Failure Drugs: What is the mechanism of action of Antiotensin Receptor Blockers (ARBs: AT1RWhat inhibitors)?
-Relax Vascular SM
(dilation; inc. flow; dec. afterload)
- dec. aldosterone (dec. preload)
- dec. NE (dec. sympathetic)
NOTE: Valsartan (AT1R inhibitor); Sacubitril (pro-drug; active neprilysin inhibitor -- breaks down natriuretic peptides)
72
Heart failure drugs: Which of the following is a positive inotropic drug?
a. B1-adrenoceptor agonist (dobutamine)
b. digitalis (digoxin and digitoxin)
c. ACE inhibitors (lisinopril)
d. ARBs (candesartan)
Answer: A and B
- B1 agonists (dobutamine)
- Phosphodiesterase inhibitors (amrinone, milrinon)
-DIgitalis (digoxin, digitoxin)
73
Endocarditis/Myocarditis:
A young, hispanic girl presents to the ER with unilateral periorbital swelling and erythematous discoloration on her eye (Romana's sign). She has developed cardiac arrhythmia and is inc. risk of fatality due to infection by this microorganism
Trypanosoma cruzi
(Chagas disease)
- SOuth AMerica/Brazil
* triatomine bugs (kissing bug) - enter host via mucous membranes
NOTE: T cruzi penetrates SM, SK and heart muscle, but primarily affects heart
74
Heart Failure Drugs: Aside from treating HF, what other disease states can ACE inhibitors help treat?
a. HTN
b. Post MI
c. DIabetes Mellitus
d. Proteinuria
e. Post-transplant
Answer ALL
75
Heart failure drugs: A patient presents with HA, dyspnea, and chest pain after being prescribed a heart failure drug.
Other adverse effects include: tolerance (downreg receptors), arrhythmias and ischemia.
The prescribed drug acts as a B-agonist. You suspect
Dobutamine
- overdose = inc. SBP
- less arrhythmogenic than milrinone
NOTE: Milrinone (PDE inhibitor) and Dobutamine (B-agonist) are both inotropic drugs.
76
Rheumatic fever: By the time RF begins, pharyngeal cultures will be negative (strep will have resolved).
In this case, what could be used to confirm a recent GAS infection?
--antistrep Ab titers
Antibody assays:
- -anti-streptolysin O (1st)
- -anti-DNAse B (2nd; if anti-strep is not elevated)
77
Myocardial Ischemia: There are two types of Acute MI -
1. _____ involves ST segment elevation. In this case, it involves the full thickness of the myocardium, and new Q waves develop.
2. _____ involves subendocardial infarction. Q waves are absent and there is NO ST elevation.
1. STEMI
2. Non-STEMI
* **high troponins
78
Myocardial Ischemia: Myocardial Oxygen supply is determined by two main factors:
1. blood flow through coronary arteries
2. oxygen carrying capacity
What can cause decreased flow through the coronary arteries?
1. Atherosclerosis **
2. Vasoconstriction
- -cocaine (a1 vasoconstrictor), amphetamines, vasospastic angina (Prinzmetal)
3. Increased HR
- -inc. systole (dec. coronary artery filling in diastole)
- -dec. blood flow to heart
79
Heart Failure: The most common type of Left Heart Failure.
Common initial insults include:
- loss of cardiac muscle secondary to ischemia
- pressure overload (HTN, aortic stenosis)
- volume overload (aortic regurg; mitral regurg.; renal failure or TACO
- cardiomyopathy
Systolic Heart failure
(Heart failure with reduced ejection fraction; HFrEF)
* dec. myocardial contractility = dec. SV and inc. LVEDV
* low EF
NOTE: Normal EF = 50-65%
NOTE 2: TACO = transfusion associated circulatory overload
80
Heart Failure: How do ACEI's and ARB's induce acute renal failure?
Inhibit Ang II (efferent arterioles)
-arteriole remains dilated - dec. GFR
**Contraindicated in renal failure
81
Angina:
1. ______ is the most common type of angina. It is caused by atherosclerotic obstruction of the large cororonary vessels.
2. _____ is a transient, reversible spasm of localized portions of the coronary blood vessels.
3. ____ is due to acute episodes, even while at rest. It may have previously been stable. It is associated with high incidence of MI and sudden death
1. Stable angine (effort)
2. Variant angina (Prinzmetal's)
3. Unstable
* *Prinzmetal's can be unstable if attacks occur w/ increasing severity/freq.
NOTE: cardiac muscle cannot develope appreciable O2 debt during stress and repay it later
82
Heart Failure: ALthough ARB's are used mainly for Tx HTN, they can also be used to treat CHF in patients who are intolerant to ACE (due to coughing)
Valsartan w/ Sacubitril (neprilysin inhibitor) is used for chronic HF.
What are the benefits of these drugs?
- less hospitalization/mortality
- better benefits in HFpEF
- approved for kids >1yr
NOTE: reduce stroke w/ cerebrovascular; reduce diabetes in type 2 (improve insulin release)
83
Myocarditis:
A young, hispanic girl presents to the ER with erythematous discoloration on her eye (Romana's sign). She has developed myocarditis with cardiac arrhythmia and is at inc. risk of fatality due to infection by this microorganism
Trypanosoma cruzi
(Chagas disease)
- SOuth AMerica/Brazil
* triatomine bugs (kissing bug) - enter host via mucous membranes
NOTE: T cruzi penetrates SM, SK and heart muscle, but primarily affects heart
84
Endocarditis: THe symptoms of infective endocarditis are often non-specific and include
- fever (MC)
- anorexia
- weight loss
- malaise
- headache
- manifestations of HF due to valve insufficiency
What are common 2ndary complications?
-focal neurologic (embolic stroke; cerebral
abscesses)
- back pain (vertebral osteomyelitis)
- renal failure (type III hypersensitivity)
- arthralgia (synovitis)
- osler nodes/Roth spots (immune-mediated vasculitis)
85
Endocarditis: Infective endocarditis is classified in several ways:
1. Temporal evolution
2. Infection site
3. Cause of Infection/Pre-disposing risk factor
True/False: With regard to site of infection, Left sided valves are most often involved. Think I.V. drug abuse if the R. side is involved.
True
86
Myocardial Infarction: Describe the classic ECG patterns seen in the walls of the heart during acute MI
1. ANterior wall infarction
2. Lateral wall infarction
3. Inferior wall infarction
4.
1. Anterior wall
- -LAD occlusion
- -Leads: V2-V4
2. Lateral wall
- -left circumflex occlusion
- -Leads I, AvL, V5-V6
3. Inferior wall
- -RCA occlusion
- -Leads II, III, aVF
NOTE: Appearance of abnormalities in a large # of leads suggests either extensive injury or concomitant pericarditis
87
Chagas disease: A patient with chronic Chagas disease typically presents 5-15 yrs post-infection. Persistence of the parasitemia leads to prolonged host immune response.
Symptoms often include arrhythmias, heart failure and chest pain along with megaesophagus and megacolon. What causes these chronic symptoms?
- Cross reaction w/ host-myocardial cells and conductance pathways
- leads to dilated cardiomyopathy or cardiac arrhythmias
Dx: Serology
NOTE: small % develop to chronic
88
Anti-arrhythmic drugs: The following describes what CLass IA drug?
1. Cardiac
-normal sinus rhythm, but 2-3x inc. in mortality
(prolongs QT interval)
2. can cause torsades de pointes
3. Increases digoxin plasma levels
4. Can be used during pregnancy
Quinidine
89
Heart Failure: In heart failure, blood backs up behind the failing ventricle. With left heart failure, blood backs up into ______ circulation due to increased hydrostatic pressure. With right heart failure, blood backs up into _____ circulation.
Left: pulmonary
--vascular congestion -- inc. hydrostatic pressure - transudation of fluid into the interstitium and alveoli -- dyspnea and orthopnea
*back up in atrium leads to overflow backward into pulmonary veins
Right: systemic venous system
--edema of lower extremities, liver, GI tract
90
Heart Failure drugs:
1. Hydralazine acts on the arterial endothelum where it dec. TPR and ______, ultimately increasing cardiac ouput and dec. O2 demand.
2. Isosorbide dinitrate increases NO levels, dilating arteries by inc. _____ levels. This increases cardiac contractility
1, Hydralazine
--dec. afterload
2. Isosorbide dinitrate
- -inc. cGMP; inc. contractility (inc. Calcium)
91
Myocardial Ischemia: Describe diagnosis and Treatment of Stable angina
1. Dx
- -stress test (ST segment depression > 1mm
(subendocard. ischemia)
2. Tx
A. Acute: rest (dec. O2 demand), Nitroglycerin (sublingual; systemic vasodilation reduces vent. wall stress)
B. To reduce episodes/improve exercise tolerance:
- -Beta blockers (dec. HR and contractility)
- -Ca2+ channel blockers (coronary; peripheral vasodilation; reduce contractility)
92
Myocardial Ischemia: A complication of STEMI that involves outpouching of scar tissue (weakened).
A common sign is:
-precordial bulge during systole (blood enters aneurysm causing ant. chest wall movement)
Ventricular aneurysm
NOTE: Complications: heart failure due to lack of contraction, clot w/ embolus, rupture is uncommon (scar is tensile)
93
Heart failure: Left sided heart failure is more common than right sided, however, failure of both ventricules can occur (biventricular failure).
There are two types of failure, backward and forward. D
1. Backward failure describes the back up of blood behind the failing ______. LHF results in pulmonary edema, and RHF results in peripheral edema (ascites, JVD and hepatomegaly).
2. Forward failure is due to decreased perfusion as a result of reduced ____. This leads to weakness and fatigue
1. Backward: Failing ventricles
| 2. Forward: Reduced CO
94
Myocardial Ischemia: Reperfusion involves restoration of blood flow to previously injured myocytes via angioplasty or thrombolytics. The sooner it is applied, the better as it limits the size of the infarct and reduced mortality.
However, it can also cause further damage, known as reperfusion injury. What are the mechanisms of reperfusion injury?
a. ROS
b. altered intracell. Ca2+ handling
c. microvascular and endothelial cell dysfunction
d. altered myocardial metabolism
e. neturophil, platelet and complement activation
all of the above
95
Myocardial Ischemia: Chest discomfort described as pressure, heaviness, squeezing. It is typically diffuse, with gradual onset and offset after 2-5 minutes.
It is the most common clinical manifestation of myocardial ischemia.
Angina pectoris
*other symptoms: nausea, fatigue, diaphoresis, SOB
96
Heart failure: Along with manifestations of pulmonary congestion (dyspnea, orthopnea, hypoxemia, bibasilar crackles) what can be seen in radiographic findings of a person w/ Left sided heart failure?
1. Cardiomegaly (>50%)
2. Pleural effusion
3. Central edema
4. Kerley B lines (interlobular edema)
5. Vascular engorgement
6. Vascular redistribution
97
Rheumatic fever: Acute Rheumatic fever normally develops 2-3 weeks after pharyngitis. It usually affects 5-15y/o.
What are the predominant clinical manifestations?
1. Arthritis (1st)
2. Carditis (most lethal)
-transmural (pancarditis)
-chronic rheumatic heart disease due to valvular fibrosis
-affects all valves
(mitral > aortic > Tri > pulm)
NOTE: chronic rheumatic heart disease is seen more in females; manifests middle age as valvular stenosis or insufficiency
98
Heart Failure Drugs: Potassium sparing diuretics include
- spironolactone and eplerenone
- amiloride and triamterene
What are the mechanisms of actions of these drugs?
1. Spironolactone/Eplerenon
- compete w/ aldosterone
- dec. gene expression of Na channels in apical membrane
- dec. Na/K pumps in basolateral (inc. Na excretion)
- dec. K+ excretion
2. Amiloride/Triamterene
- block apical Na channel
- dec. Na2+ reabsorption
99
Anti-arrhythmics: Class II drugs are B-adrenergic receptor blockers such as
1. Esmolol
2. Propanolol (B1 and B2)
3. Metoprolol
Esmolol is used in _______ ONLY. Propanolol and Metoprolol are used in _____ and _____ arrhythmias. What is their significance?
1. Esmolol
- -acute HTN emergencies only
2. Propanolol and Metoprolol
- -supravent. and vent. arrhythmias
- -dec. death after MI
* ONLY drugs that reduce mortality in asymptomatic patients
100
Anti-arrhythmics: What does long term management involve in treating atrial flutter/fib or PSVT?
1. beta blockers
- -metoprolol, propanolol
and/or non DHP Ca2+ blockers
2. amiodarone, sotalol, dofetilide, flecainide
101
Heart Failure Drugs: What are common side effects of Thiazides?
Common:
1. Most common:
- headaches, blurred vision
- postural hypotension
- allergies (sulfonamide)
2. Others:
A. electrolyte imbalance (hypokalemia; metabolic alkalosis; hypercalcemia; hyponatremia; prolonged use)
B. metabolic imbalance
(dec. insulin = insulin tolerance; hyperuricemia = gout)
102
Anti-arrhythmics: Class III drugs primarily block K+ channels.
The following describes which drug?
1. used to maintain sinus rhythm
2. bad for long term outcomes
- -prolongs QT
- -NO torsade
3. Adverse:
- blue gray discoloration
- thyroid abnormalities
* *pulmonary fibrosis
Amiodarone
Administer:
- oral (long term; atrial and vent.)
- I.V. (acute vent.; Tx w/ epinephrine)
NOTE: AVOID class III during pregnancy UNLESS a life threatening arrhythmia is present
103
Myocardial Ischemia: True/False: Over time, chronically ischemic tissue will stimulate the formation of new collateral vessels, which can often mitigate the effects of ischemia by carrying blood to under-perfused areas.
True
*angiogenesis (VEGF)
104
Myocardial Ischemia: When would we most likely see a "silent" acute MI?
-elderly, diabetics and women
105
Rheumatic fever: A patient presents with complaints of palpitations and chest pain (carditis). He also reports arthritis of the large joints (knee, shoulders). He complains it began in the legs and migrated upward.
On PE you note a rash on the trunk and arms appearing as a snake-like ring with central clearing (erythema marginatum). There are painless, firm subcutaneous nodules on the back of his wrists, elbows and knees. Patient exhibits rapid, purposeless movement (sydenham's chorea)
Hx is significant for untreated GAS infection. You suspect
JONES
*Rheumatic fever
106
Heart Failure Drugs: These K+ sparing diuretics induce
- GI disturbances (diarrhea; ulcers; common)
- Hyperkalemia (life threatening)
- Gynecomastia, impotence, dec. libido
Spironolactone and Eplerenone (steroidal)
107
Myocardial Ischemia: The most common cause of Acute MI is atherosclerosis/plaque.
Which of the following are less common causes?
a. vasculitis of coronary arteries
b. cocaine (vasoconstriction)
c. embolization (plaque from elsewhere)
d. hypercoagulability disorders
e. viral infection
Answer: A-D
*coronary artery disruption (aortic dissection - retrograde; iatrogenic - revascularization)
*Kawasaki disease
(multi-system - coronary artery aneurysms, cardiac ischemia, MI)
108
Myocardial Ischemia: STEMI involves ST segment elevation and new Q wave formation.
Common complications of STEMI include
1. Cardiogenic Shock
2. Lethal arrhythmias
3. Heart Failure
4. Rupture
5. Mural thrombus
6. Pericarditis
_________ is due to stasis within hypokinetic heart. It is associated with inc. risk of peripheral embolization
Mural thrombus
*blood clot due to stasis of blood within the heart
109
Myocardial Ischemia: True/False - Cardiac enzymes are released only when there is cell death (necrosis). Troponin is NOT released with the tissue is just ischemic.
Other causes of increased troponin include cardiac surgery and myocarditis.
True
110
Endocarditis: Infective endocarditis is classified in several ways:
1. Temporal evolution
2. Infection site
3. Cause of Infection/Pre-disposing risk factor
With regard to evolution, ______ endocarditis rapidly damages cardiac structures, seeds extracardiac sites and progresses to death within weeks (if untreated)
Acute endocarditis
111
Myocardial ischemia: A chronically ischemic heart tends to develop collateral circulation. These collaterals bypass the occlusion and help prevent MI if the main vessel is occluded.
What symptoms would you see in the patient?
- asymptomatic at rest
| - ischemia w/ exertion (can't inc. blood flow)
112
Heart failure drugs: Milrinone and amrinone are inotropic agents that act as PDE inhibitors. In doing so, they alter the intracellular movement of Ca2+.
Explain their mechanism of action
- target PDE-3 (cardiac and SM)
- inc. cAMP
- inc. calcium flux in heart during action potential
- inc. myocardial contractility
* *vasodilation
* dec. vascular resistance
113
Anti-arrhythmics: This class II (beta blocking) and III (activity) drug is NOT for patients with a QTc > 440msec. It can cause torsade de pointes and bronchospasm
Sotalol
| Class II and III
114
Angina drugs:
Which of the following is anti-thrombotic and is used for aspirin sensitive patients?
a. Clopidogrel
b. Organic nitrite and nitrate
c. ACE inhibitors
d. Calcium channel blockers
Clopidogrel
(preventive agent)
*others are anti-ischemic agents
115
Heart failure drugs: Digitalis glycosides (Digoxin; synthetic and Digitoxin; foxglove) are used in HF because they inc. contractility.
They are also used in what heart arrythmias?
atrial fibrillation
(dec. AV node conduction)
* NOT ventricular
* DO NOT dec. mortality
116
Rheumatic Fever: When do the ANti-strep and Anti-DNAse B titers rise and peak?
1. Anti-strep
- -rise 1 week
- -peak 3-6wks post-infection
2. AntiDNAse B
- -1-2 wks
- -peak 6-8 wks
117
Right heart murmurs are best heard during ______, while left heart murmurs are best heard during _____
1. Rinspiration
| 2. Lexpiration
118
Heart Failure Drugs: Vasodilators are used for HTN, angina, pre-eclampsia and HF.
Vasodilators include:
1. Hydralazine
2. Nitrates
_______ is an arterial vasodilator that acts to decrease afterload in ACUTE HF (esp. patients who cannot tolerate ACE inhibitors or are unresponsive to diuretics). It is usually used in combo w/ diuretics and sympathetic blockers
Hydralazine
*NOT monotherapy
119
Heart Failure drugs: This type of diuretic has the following features:
- rapid onset
- short duration of action (less useful for HTN)
- act in TAL (ascending)
- inhibits NKCC cotransporter (hyponatremia and diuresis)
- inc. Mg2+ excretion
- inc. Ca2+ exretion
Loop diuretics (furosamide)
Adverse effects
1. -electrolyte imbalance
2. metabolic issues
* hypocalcemia
* hypokalemia
3. ototoxicity (tinnitus, vertigo)
-ethacrynic acid
--IV large doses
(alter electrolytes in endlymph of inner ear)
120
Heart Failure Drugs: Dry cough is the most common side effect of ACE inhibitors.
What causes dry cough?
Inc. bradykinin and Substance P
-usually degraded by ACE
NOTE: bradykinin vasodilates -- inc. anti-HTN effects of ACEI's
121
Endocarditis: Which of the following is a risk factor for developing endocarditis?
1. Mitral valve prolapse
2. Degenerative valve disease
3. IV drug abuse
4. Prosthetic Heart Valves
Answer: All of the above
* Congenital valvular disease
* Previous endocard.
* Rheumatic disease
1. Mitral
- -MC underlying cardiac condition
3. IV use
- -S. aureus (predominant)
- -tricuspid valve
4. Prosthetic
- -mechanical = initially susceptible
- -bioprosthetic = inc. risk after 1 yr
122
Anti-arrhythmics: This drug is a nucleoside that is administered as a rapid IV bolus.
It is the drug of choice for prompt conversion of paroxysmal supravent. tachycardia.
Adenosine
*may be used during pregnancy
NOTE: adverse effects - flush; bronchospasm, headache
123
Heart Failure drugs: Which of the following increases Digoxin and its side effects?
a. ACE inhibitors
b. K+ sparing diuretics
c. Ca2+ channel blockers
d. Warfarin
Answer: K+ sparing diuretics
124
Myocardial Ischemia: Describe the Pathological Finding in Acute MI:
1. During first 4 hours
2. After 12-24 hrs
3. From 1-3 days
1. 1st 4 hrs.
- -no gross changes
2. 12-24 hours
- -neutrophils enter periphery
- -contraction bands (periphery; calcium influx and hypercontraction)
- -early coagulation necrosis
3. 1-3 days
- -gross: pale
- -microscopic: coagulation necrosis (myocyte nuclei and striations disappear)
- -abundant neutrophils
125
Myocardial Infarction: What are the common ECG changes seen in acute MI?
1. Inverted T wave
- -ischemia
2. ST segment elevation >1mm
- -STEMI
- -irreversibly injured myocardial cell
3. New Q waves
- -coagulative necrosis
NOTE: high probability of AMI if ST-segment elevation of > 1mm is seen in 2 anatomically contiguous leads or by presence of new Q waves. **a normal ECG does NOT exclude AMI.
126
Myocardial ischemia: Vasospastic angina results in high grade obstruction of the coronary vessels. What is the most common manifestation of this?
Transmural ischemia
- entire thickness of myocardium
* typically at rest
NOTE: complications include acute MI (w/ atherosclerosis), arrhythmias, Sudden cardiac death
127
A young female age 18 presents to the clinic with possible MI. She says she experienced dyspnea and chest discomfort/pain. Her troponin levels were elevated, but her coronary angiogram was normal.
A sample taken revealed lymphocytic infiltrate with focal myocyte necrosis.
What do you suspect?
Viral Myocarditis
* elevated troponin
* variable ECG
* normal angiogram
* Echo: key for ventricular dysfunction in myocarditis
NOTE: many recover; some dilated cardiomyopathy
128
Angina drugs - Ca2+ channel blockers:
______ (dialtizem, verapamil) ALSO decrease HR and contractility, causing further decrease in myocardial O2 demand.
*Caution w/ these drugs unless HR is elevated. It is contraindicated in Heart Failure.
Non-dihydropyridines
*dialtazem, verapamil
Normal HR: 60-100bpm
**Not for Heart Failure
129
Heart Failure Drugs: Vasodilators are used for HTN, angina, pre-eclampsia and HF.
Vasodilators include:
1. Hydralazine
2. Nitrates
Nitrates (nitroprusside) and Nesiritide (IV) are venodilators (dec. preload). When would they be used?
Neseritide (venodilator) -- acute decompensated HF
Isosorbide dinitrate and hydralazine (dec. pre/afterload) = 1st oral combo approved for African Americans
130
Anti-arrhythmics: This class III drug
- is not meant for patients with a QTc > 440 msec
- potent blocker of IKr (used to maintain sinus rhythm after a fib or flutter)
- requires titrated dose (avoid QT prolongation)
Dofetilide
*can cause torsade depointes
NOTE: it is initiated and adjusted in the hospital, with restricted access.
131
Myocardial ischemia: Reperfusion injury can occur when introducing new blood during an MI.
Common manifestations of Reperfusion injury include:
1. Myocardial stunning
2. Microvascular dysfunction
3. Lethal reperfusion injury
Describe Microvascular dysfunction
Microvascular dysfunction
- -endothelial cell dysfunction
- -vasoconstriction
- -platelets, leukocytes
- -inc. vasc. permeability
* *limits perfusion - "no reflow"
132
Angina drugs - B-adrenergic Receptor Antagonists: These drugs are NOT vasodilators.
They are useful in Stable Angine (managment of angina of effort).
What are the effects of these drugs?
- dec. HR
- dec. b.p.
- dec. contractility
* *dec. O2 demand
* prevent reflex tachy (via nitrates or dihydropyridines)
Include: Carvedilol, labetalol, acebutalol, metoprolol and propranolol
NOTE: NOT for variant or acute angina
133
Anti-arrhythmics: Procainamide is a class IA drug that induces adverse effects similar to quinidine.
Long term procainamide therapy can produce a ______ syndrome in 1/3 of patients
Transient lupus erythematosus-like syndrome (arthritis and arthralgia)
NOTE: can be used ACUTELY during pregnancy
134
Heart failure drugs: Milrinone (PDE inhibitor) and Dobutamine (B-agonist) are both inotropic drugs.
Which of these two drugs has the following adverse effects:
1. Thrombocytopenia
2. Liver toxicity
3. Nausea and vomiting
4. Mortality w/ long term use
5. OVerdose -- hypotension via vasodilation
Milrinone
* good during short term use
* fewer adverse effects than amrinone
135
Anti-arrythmics: Differentiate between channel level and tissue level
Channel level:
-Closed > Open > Inactivated > Closed
* closed channels CAN be opened
* inactivated channels CANNOT be opened (refractory)
Tissue Level: Excitable (rest) > Excited (act. pot.) > Refractory > Excitable
NOTE: at rest, channels are CLOSED
136
A patient presnts with dyspnea, crackles, and cough with fatigure.
Upon assessment, you find they have a pansystolic murmur. What is their disorder?
Mitral regurgitation
137
Heart failure: Describe the S3 and S4 heart sounds heard in relation to heart failure
1. S3 (after S2)
- -aortic regurg; heart failure
- -normal in children and young adults (under 40)
- overly compliant/volume overloaded ventricle
* *Ken tuc ky
2. S4 (before S1)
- -LVH
- -"atrial kick" (late diastole; never normal)
- -stiff or overloaded ventricle
* *Ten nes see
138
Myocardial Infarction: Myocardial Ischemia: STEMI involves ST segment elevation and new Q wave formation.
Common complications of STEMI include
1. Cardiogenic Shock
2. Lethal arrhythmias
3. Heart Failure
4. Rupture
5. Mural thrombus
6. Pericarditis
7. Ventricular aneurysm
________ usually occurs between 1-7 days post-MI. It presents with chest pain and friction rub. It is relieved by leaning forward.
Pericarditis
* Dressler syndrome (autoimmune pericarditis)
- -2-8 wks post-cardiac injury
- -auto-Abs against damaged heart muscle
139
Heart Failure Drugs: In patient's with heart failure, ACE inhibitos help to lower blood pressure while increasing blood to the heart.
What is its mechanism of action?
1. arterial dilation (dec. afterload)
2. coronary dilation (inc. blood flow to heart)
3. dec. aldosterone
(dec. volume; dec. preload)
4. decrease mortality
140
Heart failure drugs: Which of the following are drugs that decrease resistance (TPR)?
a. ACE inhibitors (lisinopril)
b. ARBs (AT1RI's; candesartan)
c. B1-antagonists (carvedilol)
d. Arterial and Venous vasodilators
e. Diuretics
Answer: All of the above
- arterial vasodilators (hydralazine)
- venous (neseritide)
141
Heart failure drugs:
1. DIuretics are combined with ______ as 1st line therapy for HTN.
--better outcome than monotherapy to decrease HTN (esp. in African American patients)
ACE, ARB's and B-blockers
142
Anti-arrhythmics: Lidocaine is a class 1B drug that can induce arrhythmia, heart block or bradycardia.
True/False: It can be used during pregnancy.
True
143
Myocardial Ischemia: STEMI involves ST segment elevation and new Q wave formation.
1/3 of patients w/ STEMI die within 24 hours, but this can vary depending on the extend of the infarct, and LV function. Survivors tend to have residual cardiac dysfunction.
Common complications of STEMI include
1. Cardiogenic Shock
2. Lethal arrhythmias
3. Heart Failure
4. Rupture
5. Mural thrombus
6. Pericarditis
The most common overall arrhythmias associated with STEMI are ______, but the most common fatalities are due to _______.
Most common overall arrhythmias: Premature ventricular contractions (PVC)
Most common cause of death: V-fib
144
Anti-arrhythmic drugs: Increased automaticity of the heart can be caused by any change that decreases the time required for depolarization and causes a shift in the threshold potential.
1. Parasympathetic stimulation makes the slope of depolarization more shallow, thus taking ____ to reach threshold.
2. Sympathetic stimulation makes the slope steeper, thus taking ______ amount of time to get to threshold
1. Parasymp: longer
| 2. Symp: shorter
145
Heart Failure: ACE inhibitors interact with the following drugs:
- antacids
- iron salts
- K+sparing diuretics
What effects do they cause?
Antacids: dec. absorption
Iron salts: dec. efficacy
K+ sparing: inc. hyperkalemia; vasodilation
146
Angina drugs - Nitrates/Nitrites:
They are NOT for use within 24 hours of ______ and ______ or 48 hours of tadalafil use. They may also cause hypotension, dizziness and syncope
24 hours: sildenafil, vardenafil
48 hrs: tadalafil
Major effects: orthostatic hypotension, tachycardia, throbbing headache
*prolonged exposure: tachyphylaxis (tolerance)
147
Heart Failure Drugs: How do ACEI's produce hyperkalemia?
They inhibit aldosterone
| decrease potassium excretion via Na/K+ pump
148
A 58 year old caucasian female presents with difficulty breathing.
She claims that it worsens at night when she is lying down. She uses 2 pillows to prop herself up, which improves her breathing.
S3 and S4 sounds are heard on auscultation as well as a pansystolic murmur.
What is her disorder?
Left sided heart failure
1. S3 = 1st cardiac sign of HF
2. Functional MV regurg:
- -stretched annulus due to LVEDV
3. Orthopnea:
- -discomfort breathing while lying down
- -fluid redistributes from splanchnic into central circulation during recumbancy
* *# of pillows
* *sitting up inc. gravity -- redistribute fluid/dec. preload
4. Paroxysmal nocturnal dyspnea
- -dyspnea that awakens patient from sleep
- -wheezing and coughing
149
Anti-arrhythmics: Class I C drugs are open channel blockers and include the oral drugs _____ and ____.
Flecainide and Propafenone (both oral)
150
Heart failure drugs: What are the adverse effects of Beta blockers?
- bradycardia
- hypOtension
- SOB
- drowsiness, depression
- Reynaud's (numb cold)
- sexual dysfunction
- bronchospasm (non-selective)
**Glucagon (Tx B-blocker overdose)
151
Myocardial ischemia: Calculate Heart Rate
1. 300/number of large boxes OR
2. #'s
3. Count # QRS complexes b/t 6 sec time markers x10
```
300
150
100
75
60
50
43
37
```
152
Endocarditis: Infective endocarditis is classified in several ways:
1. Temporal evolution
2. Infection site
3. Cause of Infection/Pre-disposing risk factor
With regard to evolution, ______ follows an indolent course, causing slow structural damage to the heart. It rarely metastasizes and gradually progresses (unless complicated by embolism).
Subacute endocarditis
153
Myocardial Ischemia: Acute coronary syndrome refers to
1. Unstable Angina
2. Acute MI
a. Non-ST segment (NSTEMI)
b. ST-segment MI (STEMI)
______ is a pattern of increasingly frequent, increasingly severe (prolonged; > 20min) angina that is not related to exercise and is not relieved by rest.
Unstable angina
- not relieved by rest
- not associated w/ exercise
* NO ST segment elevation
* NO troponin elevation
NOTE: if ST elevation (STEMI); if troponin elevation (NSTEMI)
154
What are the effects of pre-load and afterload on heart murmurs?
1. Inc. preload
2. Dec. preload
3. Inc. afterload
4. Dec. afterload
1. Inc preload (squat, sit, leg raise)
- --louder murmuer
2. Dec. preload (valsalva)
- -dec. blood to heart
- -soft murmur
3. Inc. afterload (hand grip)
- -louder regurg.
4. Dec. afterload (amyl nitrite)
- -louder prolapse
155
Angina drugs - Nitrates and Nitrites: These drugs relax SM in stable angina.
Low concentrations of organic nitrates _____ veins which predominates over arterioles.
Arteriodilation also helps cause dec. afterload.
Nitrates: Venodilation
- inc. venous capacitance = dec. ventricular EDV (preload)
- inc. subendocardial perfusion
- dec. myocardial O2 demand
156
Myocardial Ischemia: Because the myocardium cannot increase O2 extraction, an increase in O2 demand requires increased perfusion (blood flow).
Which of the following are determinants of oxygen demand?
a. HR
b. myocardial contractility
c. myocardial wall tension
d. systolic b.p.
All of the above
* Wall tension:
- -product of preload and myocardial muscle mass
- -inc. tension = inc. O2 demand
*Also: physical activity, thryotoxicosis, aortic stenosis, cocaine/amphetamines inc. O2 demand
157
Murmurs: "Myxomatous degeneration of the valve leaflets.
A patient presents with a mid-systolic click, then murmur of mitral regurgitation
Mitral valve prolapse
*click - snapping of chordae tendinae
158
Myocardial ischemia: Reperfusion injury can occur when introducing new blood during an MI.
Common manifestations of Reperfusion injury include:
1. Myocardial stunning
2. Microvascular dysfunction
3. Lethal reperfusion injury
_______ is prolonged contractile dysfunction. It is reversible, but the heart needs time to recover.
1. Myocardial stunning
159
Angina drugs: What are the steps in treating Acute MI?
MONA
1. Oxygen (only if needed (pulse-ox)
2. Nitrates
3. Aspirin
4. IV started
5. Beta blockers (if tachy and NOT in HF)
6. Maybe Morphine
NOTE: normal pulse ox = 98%
160
Myocardial Ischemia: ________ refers to death from cardiac cause within 1 hour of symptom onset.
Risk factors include:
1. ***Ischemic heart disease
2. Obesity
3. Diabetes
4. Hyperlipidemia
5. HTN
6. Smoking
7. Previous MI
Sudden cardiac death
Nont-coronary artery causes:
- cardiomyopathies
- aortic stenosis
- cocaine
- myocarditis
- conduction defects
161
Angina drugs: Nitrates and Nitrites are useful agents for the treatment of angina.
__________ is the most frequently used agent for immediate treatment of angina because of its rapid onset of action. However, it is not a good choice for maintenance therapy (b/c of duration).
Sublingual nitroglycerin
NOTE: Slowly absorbed preps are buccal, oral, transderm (maintenance therapy; risk tolerance)
--reduce tolerance w/ nitrate free period (8-10hrs observed)
162
Heart failure drugs: What is the mechanism of action of Digoxin (digitalis glycoside)?
1. inhibits Na ATPase in sarcolemma
2. Inc. Na
3. Inc. Na/Ca exchanger
4. Inc. Ca2+ in myocytes
5. inc. contractility and SV at any given preload
Indirect:
- inc. vagal activity
- dec. AV node conduction
- dec. heart rate (neg. chronotropy)
163
Myocardial Ischemia: Laboratory diagnosis of acute MI involves serial testing for cardiac _____, which are specific for myocardial injury (because they regulate Ca3+ mediated muscle contraction.)
Troponins
* appear 3-12 hours, peak at 24 and disappear within 7-10 days
* Troponin stays positive for 7-10 days
NOTE: use serial testing since it may take a few hours to rise
NOTE 2: ECG BEST test for early diagnosis; confirms in 80%
164
Heart Failure: Excessive fluid retention leads to
- inc. LVEDV/LVEDP
- inc. PWCP
- pulmonary edema and SOB
What is released upon increased fluid and ventricular stretching?
BNP
-released from ventricles (when stretched)
- natriuretic
- relieves workload on heart
- Diagnostic
165
Myocardial Ischemia: Acute coronary syndrome is usually due to plaque disruption associated w/ thrombosis (clot formation). This leads to severe, transient reduction in coronary blood flow. It can ultimately result in unstable angina, or worse, acute MI.
Describe the pathogenesis of acute coronary syndrome and how it leads to thrombus formation.
1. Atherosclerotic plaques
- -foam cells and SM cells accumulate
2. Oxidized LDL within foam cells contains cytotoxic, chemotactic and procoagulant agents
3. Thinning of fibromuscular cap
- -as plaque grows
- -macrophage proteases
- -neutrophil elastases
4. Plaque fissure/rupture
- -due to mechanical stress
5. Adhesion and aggregation of platelets
- -coagulation pathway activated
6. Blood clot forms
- -obstructs blood flow
- -ischemia
166
Myocardial Ischemia: Atherosclerosis (the major cause of Myocardial Ischemia) can be caused by metabolic syndrome.
To have metabolic syndrome, a person must have 3 out of 5 of the following criteria:
1. Hyperinsulinemia
2. Obesity
3. Dec. HDL
4. Hypertriglyceridemia
5. Increased b.p.
What are the values?
1. Hyperinsulinemia (glucose >100mg/dL)
2. Obesity (waist >40 men; >35 women)
3. Decreased HDL (<40mg/dL men; <50mg/dL women)
4. HyperTG (>150mg)
5. Increased b.p./HTN (>130/85mmHg)
167
Heart failure: A patient presents with hepatosplenomegaly, peripheral edema and JVD (dec. venous return from the head).
You suspect heart failure of the ________ side
Right side
-failure of RV leads to inc. pressure within the RA --- increased pressure within the RA impairs venous return from the body
NOTE: Right sided heart failure (RV failure) is most commonly caused by LV failure.
168
Heart failure drugs: Dobutamine is a B-agonist with positive inotropic activity (inc. force of contraction).
It also has a mild positive chronotropic effect (inc. rate of contraction).
What other effects does dobutamine have?
- inotropic (B1), chronotropic
- vasodilator (B2 agonist)
- dec. ventricular filling pressure (preload)
- improves output (afterload) w/out inc. O2 demand
169
Myocardial ischemia: Sudden cardiac death pathogenesis differs b/t children and adults.
What is the most common cause of death in children? in adults?
1. Children
- aortic stenosis***
- hypertrophic cadiomyopathy
2. Adults
- -Lethal arrhythmia
- -disrupted atherosclerotic plaque with subsequent thrombus formation (AMI)
170
Myocardial Ischemia: Describe the pathologic finding during acute MI 7-10 days post-MI
- Yellow necrosis
- Granulation tissue and collagen = well developed
NOTE: non-infarcted myocardium = red
- -acute infarct: pale tan
- -old infarct: white
171
Anti-arrhythmic drugs: Arrhythmias result in decreased cardiac ouput and can cause ischemia, syncope, or sudden death.
True/False: Anti-arrhythmic drugs may be life saving in moderately severe to highly symptomatic patients. They are NOT meant for mild arrhythmias.
True
172
Heart Failure: Heart failure is a clinical syndrome that occurs when the CO is inadequate to meet physiologic demands at normal filling pressures.
Manifestations include
- Fatigue
- SOB
- Edema
How does the body respond to heart failure (compensate)?
1. Baroreceptors
- -changes in pressure (tension) of arterial wall
- -nucleus tractus solitarus -- vasomotor center
* inc. sympathetic (inc. contractility)
2. RAAS -- sodium and water retention
- -response to dec. renal perfusion from dec. CO
NOTE: Though initially helpful, over time, these mechanisms lead to changes (loss of myocytes, fibrosis) that contribute negatively on heart function. **This is why drugs that antagonize these systems are used to Tx HF.
173
Anti-arrhythmics: This drug is given as an IV to suppress drug-induced arrhythmias.
Mg Sulfate
**1st choce if Torsades de Pointe (fix electrolyte imbalance)
174
What improves mitral valve prolapse? What makes it worse?
Better:
--Squatting (inc. blood volume in LV -- delays prolapse)
Worse:
--Standing (dec. blood volume)
175
Anti-arrhythmics: List the order for Tx of Ventricular arrhythmias
1/2. Drugs to convert rhythm
--amiodarone (w/ epi), lidocaine, procainamide, adenosine, verapamil, metoprolol
1/2: Cardioversion (if drugs don't works; or 1st choice if vent. fibrillation)
NOTE: Mg IV is 1st in the case of torsade/drug induced arrhythmias (w/ isoproterenol)
3/4. Long term management
- -mexiletine, sotalol, flecainide (primary)
- -amiodarone (secondary)
3/4. Catheter/surgical oblation; pacemaker; cardioverter-defibrillator
176
Myocardial Ischemia: ______ refers to progressive HF resulting from long-term ischemic damage to the myocardium. Typically the damaged myocardium is replaced by scar tissue.
Clinical findings include:
1. biventricular heart failure
2. angina pectoris
3. evolution into dilated cardiomyopathy
Chronic ischemic heart disease
177
Angina:
1. ______ is the most common type of angina. It is caused by atherosclerotic obstruction of the large cororonary vessels.
2. _____ is a transient, reversible spasm of localized portions of the coronary blood vessels.
3. ____ is due to acute episodes, even while at rest. It may have previously been stable. It is associated with high incidence of MI and sudden death
1. Stable angine (effort)
2. Variant angina (Prinzmetal's)
3. Unstable
- -plaque rupture/platelets
* *Prinzmetal's can be unstable if attacks occur w/ increasing severity/freq.
178
Anti-arrythmic drugs: Class IB drugs are inactivated channel blockers and include Lidocaine and Mexiletine.
What are their features?
1. Lidocaine (IV)
- -elimination: 1.5 hours
- -acute vent. arrhythmias
2. Mexiletine (oral)
- -10 hrs
- -eliminates: 11hrs
- -lng-term prophylaxis
179
Heart failure: Which of the following tests may be used to diagnose heart failure?
a. Angiogram
b. Echo
c. BNP and N=terminal pro-BNP
d. ECG
e. Chest X-ray
Answer: B-E
1. Echo:
- -EF measures function
- -valvular function
- -indicative of prior MI
2. BNP
- -released when stretched (heart failure)
- -diagnose and prognosis
3. ECG
- -cardiac rhythm
- -LCH or prior MI (Q waves)
- -normal ECG excluded LV systolic dysfunction
4. Chest X-ray
- -cardiac size, pulmonary
180
Heart Failure drugs: Digoxin Toxicity (>1.2ng/ml) typically presents with which of the following symptoms?
a. altered color perception
b. bradycardia (enhanced vagal effect)
c. paroxysmal atrail tachycardia with AV block
d. regularized atrial fibrillation
Answer: All of the above
Digitalis derivatives: low therapeutic index
Digoxin/Digitoxin overdose can be treated with dogixin/digitoxin antibody
