Cardio Flashcards 1
What are the cardinal symptoms of cardiac disease?
Chest pain - myocardium
Shortness of Breath - pulmonary artery HTN due to backup
Cough
Palpitation - awareness of heartbeat
Syncope - lost of posture/consciousness
What are non-specific symptoms of heart disease?
Abdominal pain/distention
Nasuea, vomiting
Polyuria, nocturia
Confusion, dizziness
Easy fatigability
What is systole?
Ventricular contration
What is diastole?
Atrial contraction, ventricular filling
What defines a pulse?
A wave along the arterial wall plus the reflected wave from the periphery, whose summation gives a waveform of the following form:
What defines tachycardia?
Resting HR greater than 100 bpm
What defines bradycardia?
Resting HR less than 60 bpm
What is pulsus alternans?
Seen in Left Ventricular systolic dysfunction
There is a change in strength of pulse from beat to beat
What is pulsus bigeminus?
Caused by regular bigemina dysrhythmias such as PVCs and PACs (premature ventricular/ premature atrial contractions)
normal + early beat due to premature contractions
What is pulsus bisferiens?
Seen in aortic regurgitation with or without stenosis, hypertrophic cardiomyopathy
Has multiple peaks at contraction - outflow obstruction with ejection occuring
What is pulsus paradoxus?
Seen in cardiac tamponade, constrictive pericarditis, obstructive lung disease
See changes in ventricular volume filling with breathing
Pericardial pressure exceeds chamber pressure of the sounds.
May hear heart sounds, but no pulse
What is a water-hammer pulse?
Seen in aortic regurgitation, fever, anemial, thyrotoxicosis, arteriovenous fistula, chronic alcoholism (all of these cause high volumes
What is jugular venous pressure and what is it useful for?
Internal jugular vein pressure - gives an assesment of Right Atrial pressure
Measured upright and at 30-45 degrees
Jugular Venous Distension (JVD) is an abnormal finding
What is the hepato-jugular reflex?
Assessment of RV function - press on abdomen, and you will normally see that the right heart accomodates for this within a heartbeat or two. Otherwise you may see prolonged JVD
Which segments of a jugular venous pressure waveform correspond to which aspects of a cardiac cycle?
What is S1 and where do you hear it best?
S1 is produced by the closing of the mitral and tricuspid valves
Best heard over the apex
Which heart sound is produced by the closing of the mitral and tricuspid valves?
S1
What conditions does an accentuated S1 heart sound indicate?
Shortened PR interval
Mid mitral stenosis
High cardiac output states
What conditions does a diminished S1 heart sound indicate?
Lengthened PR interval
Mitral regurgitation
Severe mitral stenosis
Stiff left ventricle (systemic HTN)
What is the S2 heart sound?
Produced by the closing of the pulmonary and aortic valve
What heart sound is produced by the pulmonary and aortic valve closure?
S2
What does a loud S2 indicate?
Aortic origin - systemic HTN, aortic aneurysm
Pulmonary origin - Pulmonary HTN, atrial septal defect
What does wide S2 splitting indicate?
Right bundle branch block or pulmonary stenosis
What does Fixed splitting of S2 indicate?
Atrial septal defect
What does paradoxical S2 splitting indicate?
Left bundle branch block or severe aortic stenosis
What is S3?
Dull, low pitched sound best heard with the bell of stethoscope that indicates volume overload or increased flow through mitral/tricuspid valve
What is S4?
Dull, low-pitched sound best heard with the bell of the stethoscope that indicates decrease in ventricular compliance resulting from ventricular hypertrophy
How do you describe a murmur?
Timing
Area of maximum intensity
Grading
Position best heard
Configuration (diamond shape, cresendo/decresendo….)
Respiratory variation
Conduction
What do the grades of systolic murmors correspond to?
Grade 1/6: barely audible (cardiologist)
Grade 2/6: faint but immediately audible (resident)
Grade 3/6: easily heard (med student)
Grade 4/6: with thrill (Four = four-nicate = its a thrill!)
Grade 5/6: very loud, heard with stethoscope lightly on chest
Grade 6/6: audible without the stethoscope on the chest
What are innocent murmurs?
Common in asymptomatic adults (common in pregnancy)
Heard on physical, but no other assoicated findings
What type of murmur is produced by aortic stenosis?
Systolic murmur
Has crescendo/decrescendo
Listen at right sternal edge, 2nd ICS w/ patient upright
What type of murmur is heard in mitral stenosis?
Diastolic murmur
Mid-diastolic murmur; augmented by rapid, deep inspirations or mild exercise
Listen to apex of heart w/ patient in left lateral position
What type of murmur is produced by mitral regurgitation?
Systolic murmur
Best heard at apex of heart with radiation to left sternal edge
What type of murmur is produced by aortic regurgitation?
Diastolic murmur
Best heard along lower left sternal border
What type of murmur is produced by a patent ductus arteriosus?
Continuous murmur
What information is given by a 12-lead EKG?
A recording of the electrical activity of the heart at a specific moment in time
Tells of depolarization and repolarization of the atria and ventricles
Can tell of heart geometry and metabolic state of the heart
What do you look for in an EKG reading?
Rate
Intervals (PR/QRS/QT)
Rhythm
Axis
Hypertrophy
Infarct/Ischemia
Which EKG leads are the precordial leads?
V1 to V6
Which EKG leads are the limb leads?
VI, VII, VIII, aVR, aVL, aVF
What is the placement of the six chest leads?
What is Einthoven’s triangle?
The comination of EKG leads VI, VII, and VIII
What is the directionality of VI?
Right arm to left arm:
What is the directionality of lead VII?
Right arm to left foot
What is the directionality of EKG lead VIII?
Left arm to left foot
What is the alignment of the limb leads on an EKG (i.e aVR, aVL, aVF, I, II, III)?
What is the p wave of an EKG?
Sequential depolarization of the right atria and left atria
What is the QRS complex of an EKG?
Right and left ventricular depolarization
What is the T wave of an EKG?
Ventricular repolarization
What is the PR interval?
Interval from onset of atrial depolarization to onset of ventricular muscle depolarization
What is the QRS interval?
Duration of ventricular depolarization
What is the QT interval?
Duration of ventricular depolarization
What is measured along x axis of EKG?
Time - usually 5mm = 0.2 seconds, 1mm = 0.04 seconds
What is measured along the y axis of the EKG?
Voltage
1mm = 0.1 mV
5mm = 0.5 mV
What is a normal PR interval?
120-200ms
What is a normal QRS interval?
<110ms
What is a normal QTc interval (QT interval)?
< 460ms
What is a good rule of thumb to calculate pulse rates on EKG?
Rate = 300 / # of boxes
What is a quick way to look at axis on EKG?
Lead I and Lead aVF (Is? Fine?)
Left hand first - thumbs up? (VI)
Right hand - thumbs up? (aVF)
Both good - normal
I good, aVF bad - left axis deviation
I bad, aVF good - right axis deviation
Both bad - extreme right axis deviation
How can you tell if there is left axis deviation on EKG?
Lead I is positive and aVF is negative
How can you tell if there is right axis deviation on EKG?
Lead I is negative and aVF is positive
How can you tell if there is extreme right axis deviation on EKG?
Both VI and aVF are negative
What causes right axis deviatioN?
Right Ventricular Hypertrophy (most common)
Chronic lung diseases, emboli, and others
What causes left axis deviation?
Left ventricular hypertrophy, left bundle branch block, and others
What assesments of cardiac function can you make from a chest x-ray?
Evaluate size of heart chambers and pulmonary consequences of heart disease
Dilations and gross anatomical deformations
What indicates enlarged heart on x-ray?
If the cardiac:thoracic ratio is over 0.5
Normal is 0.45
What is a normal cardiac:thoracic ratio?
0.45
Enlarged if greater than 0.5
What assesments of cardiac function can be made via an echocardiogram?
Anatomical relationships of movement
Valve and wall motion abnormalities
Doppler for blood flow direction, velocity, turbulence, and estimation of pressure gradients
What is special about trans-esophageal echocardiography?
Can get closer to the heart and use higher frequency in order to retrieve higher resolution images
What assesment of cardiac function can a CT scan perform?
Can look for calcium deposition in coronary arteries
Diseases of the pericardium
Aortic Dissection and aneurysm
What assessment of cardiac function does cardiac catheterization provide?
Measurement of the pressure in all of the chambers of the heart, the pulmonary artery, and the aorta
What are the normal pressures in the heart chambers and great vessels?
RA: 2-8
RV: 15-30/2-8
LA: 2-10
LV: 100-140/3-12
Aorta: 100-140/60-90
Pulm: 15-30/4-12
What is the normal pressure in the right atrium?
8-Feb
What is the normal pressure in the right ventricle?
15-30/2-8
What is the normal pressure in the pulmonary artery?
15-30/4-12
What is the normal pressure in the left atrium?
10-Feb
What is the normal pressure in the left ventricle?
100-140/3-12
What is the normal pressure in the aorta?
100-140/60-90
What assesment of cardiac function can contrast angiography provide?
Imaging of internal structures that are otherwise difficult to see on x-ray
Valvular insufficiency, intracardiac shunts, severity of coronary artery artherosclerosis
What is the definition of heart failure?
A structural or functional cardiac disorder that impairs the ability of the ventricles to eject blood (forward failure) or fill with blood (backward failure) or both
Not being able to move blood without higher filling pressure
What is forward failure?
An impairment in the ability of ventricles to eject blood
What is backward failure?
An impairment in the ability of ventricles to fill with blood
What are the mediators of cardiac output?
CO = HR x SV
SV = Stroke volume, comprised of Preload, Afterload, Contractility
Draw a normal Pressure-Volume Curve
What changes do you see in a pressure-volume loop with varying preload and constant pressure (afterload) and contractility?
What does this pressure-volume loop represent?
Varying preload with constant pressure (afterload) and contractility
What changes do you see in a pressure-volume loop with varying contractility and constant pressure (afterload) and preload?
What is the following pressure-volume loop indicative of:
Varying contractility with constant preload and pressure (afterload)
What do you see in a pressure-volume loop with varying pressure (afterload) and constant preload and contractility?
What is the following pressure-volume loop indicative of
Varying pressure (afterload) with constant preload and contractility
What type of heart failure do you see with decreased cardiac output, decreased left ventricular ejection fraction, or decreased contractility?
Systolic
What changes can you see in systolic heart failure?
Decreased cardiac output
Decreased LV ejection fraction
Dereased contractility
What is a normal ejection fraction?
Over 55%
What type of heart failure do you see elevated left, right end-diastolic pressures, with normal left ventricular ejection fractions?
Diastolic
What changes do you see in diastolic heart failure?
Elevated LV, RV end-diastolic pressures
Normal LV ejection fraction
How do you calculate/define ejection fraction?
EF = SV/EDV x 100
Stroke volume / End diastolic volume
What are potential etiologies of systolic heart failure?
Impaired contractility: CAD/MI, chronic volume overload(Mitral or Aortic Regurgitation), dilated cardiomyopathy
Increased afterload: Aortic stenosis, hypertension
What is the main difference between systolic and diastolic heart dysfunction?
Systolic dysfunction has reduced ejecton fraction (<50%)
What are potential etiologies of diastolic heart dysfunction?
Impaired diastolic filling: LV hypertrophy, restrictive cardiomyopathy, myocardial fibrosis, pericardial tamponade/constriction
What changes occur in the pressure-volume loops during systolic dysfunction?
What changes occur in the pressure-volume loops during diastolic dysfunction?
What are three compensatory mechanisms that can be activated during heart failure?
Frank-Starling Mechanism
Ventricular Hypertrophy
Neurohormonal Activation
What occurs during Frank-Starling compensation for heart failure?
Increase pressures to try to maintain cardiac output
During what type of heart failure do you see Frank-Starling compensation?
Systolic
How does hypertrophy help a failing ventricle?
Hypertrophy is a compensatory mechanism to reduce wall stress
Occurs more for diastolic heart failure
During which type of heart failure do you generally see hypertrophy as a compensatory mechanism?
Diastolic
Try to reduce wall stress by increasing thickness
What are two types of ventricular hypertrophy and when are they precipitated?
Eccentric - volume overload (chamber dilation): new sarcomeres are in series with old ones
Concentric - pressure overload: new sarcomeres in parallel with old ones
What is concentric hypertrophy?
Usually brought about due to pressure overload
Hypertrophy where new sarcomeres are in parallel with old
What is eccentric hypertrophy?
Ventricular hypertrophy brought about as a compensation for volume overload (chamber dilation)
New sarcomeres are in series with old
In what type of ventricular hypertrophy are new sarcomeres in parallel with old ones?
Concentric (pressure overload)
In what type of ventricular hypertrophy are new sarcomeres in series with old?
Eccentric (volume overload)
What type of ventricular hypertrophy does volume overload (chamber dilation) generally cause?
Eccentric
What type of ventricular hypertrophy does pressure overload generally cause?
Concentric
What are neurohormonal compensatory mechanisms in heart failure?
Adrenergic nervous system
Renin-angiotensin-aldosterone system (RAAS)
Antidiuretic hormone (ADH)
How does the adrenergic nervous system work to compensate for heart failure?
Systemic vascular resistance:
BP = CO + TPR
How does the Renin-Angiotensin-Aldosterone system work to compensate for heart failure?
NaCl and water retention increases circulating volume and therefore preload
Vasoconstriction maintains blood pressure but can add to afterload too
How does Antidiuretic Hormone act as a compensatory mechanism for heart failure?
NaCl and water retention whcih increases intravascular volume, increasing preload
What are some clinical manifestations (symptoms) of left sided heart failure?
Dyspnea (on exertion or at rest)
Orthopnea (needing to sleep erect)
Cough
Paroxysmal Nocturnal Dyspnea
Fatigue
What are some clinical manifestations (symptoms) of right sided heart failure?
Edema (peripheral, or ascites)
Right upper quadrant pain
Anorexia
Which side of the heart is likely to be failing when a patient presents with dyspnea, orthopnea, cough, paroxysmal nocturnal dyspnea, or fatigue?
Left sided heart failure
What side of the heart is likely to be failing if a patient presents with edema (peripheral or ascites), right upper quadrant pain, or anorexia?
Right sided heart failure
What are some signs on exam of left ventricular failure?
Tachycardia
Tachypnea
Rales
Pleural Effusion
Loud P2
S3 (systolic dysfunction)
S4 (diastolic dysfunction)
What are some signs on exam of right ventricular failure?
JVD
Hepatomegaly
Peripheral edema
If, upon exam, you find a patient has tachycardia, tachypnea, rales, pleural effusion, loud P2, S3 and/or S4, which ventricle do you suspect could be failing?
Left Ventricle
If, upon exam, you find a patient has JVD, hepatomegaly, and/or peripheral edema, which ventricle would you suspect to be failing?
Right ventricular failure
What are you likely to find upon chest x ray of a patient with heart failure?
Cardiomegaly
Vascular redistribution (interstitial edema)
Alveolar edema
Pleural effusion, bilaterally
What are goals of treatment for patients with heart failure with reduced ejection fraction?
Identify and correct underlying disease
Eliminate precipitating causes
Manage symptoms (decrease congestion, increase cardiac output)
Modulate neurohumoral response
Prolong long term survival
What are some therapies that can reduce mortality in heart failure?
ACE Inhibitors/Angiotensin Receptor Blockers
Beta blockers (acute - make it worse; chronic - may help)
Aldosterone antagonists
Hydralazine-Isosorbide dinitrate
ICD (implantable cardioverter defibrillator)
Cardiac resynchronisation + ICD
How/why are diuretics useful in treating heart failure?
Promote elimination of Na and water via the kidney
Reduce venous return to the heart, releive pulmonary congestion
There is no mortality benefit, only symptomatic releif
Overshooting it can lead to decreased CO
Do diuretics help reduce mortality in heart failure?
NO - only provide symptomatic releif
What is an example of a venous vasodilator?
Nitrates
What is an example of an arteriolar vasodilator?
Hydralazine
What is an examle of arteriolar and venous dilators?
ACE Inhibitors/Angiotensin Receptor Blockers (ARBs)
How do venous vasodilators work to treat heart failure?
Increase venous pooling, causing a decrease in the venous return to the heart
e.g. nitrates
How do arteriolar vasodilators work to treat heart failure?
Decreased systemic vascular resistance causes decreased LV afterload, increasing the stroke volume
e.g. Hydralazine
How do ACE inhibitors work?
Inhibit formation of Angiotensin II, decrease aldosterone
This increases the rate of Na+ elimination, decreasing the intravascular blood volume
As a result, this prevents the maladaptive ventricular remodeling of hypertrophy…
What are treatment options in the event that ACE inhibitors are not well tolerated?
ARBs
What are some beta blockers?
carvedilol, metroprolol, bisoprolol
improve overall and event free survival of all classifications of heart failure (NYHA classifications)
When are beta blockers contraindicated?
HR < 60 bpm
symptomatic bradycardia
Signs of peripheral hypoperfusion
COPD, Asthma
PR interval greater than 240 ms (2nd or 3rd AV block)
How does ionotropic therapy work?
Inhibits Na-K ATPase, causing an increase in intracellular Ca++, increasing contractility
When do you give ionotropic therapy?
In patients with heart failure in order to control symptoms
Significantly reduces hospitalization rates for heart failure, but does not provide benefit in terms of overall mortality
What is a phosphodiesterase inhibitor and when is it generally given?
Milrinone - only given in acute congestive heart failure
What is a beta agonist and when is it given?
Dopamine, dobutamine; only given in actue congestive heart failure
What are aldosterone antagonists and when are they given?
Spironolactone, eplerenone; act to increase diuresis and improves survival in congestive heart failure
What class of drug is spironolactone?
Aldosterone antagonist
Increases diuresis (improves survival in congestive heart failure)
What class of drug is eplerenone?
Aldosterone antagonist
Increases diuresis (improves survival in congestive heart failure)
What class of drug is dopamine?
Beta agonist - given in acute congestive heart failure
What class of drug is dobutamine?
beta agonist; given in acute congestive heart failure
What class of drug is milrinone?
Phosphodiesterase inhibitor; given in acute congestive heart failure
What class of drug is digitalis?
ionotropic
What class of drug is carvedilol?
Beta blocker - improves event-free survival of heart failure
contraindicated with heart rate <60bpm, symptomatic bradycardia, signs of peripheral hypoperfusion, asthma/COPD, PR interval greater than 240ms
What class of drug is metoprolol?
Beta blocker - improves event-free survival of heart failure
contraindicated with heart rate <60bpm, symptomatic bradycardia, signs of peripheral hypoperfusion, asthma/COPD, PR interval greater than 240ms
What class of drug is bisoprolol?
Beta blocker - improves event-free survival of heart failure
contraindicated with heart rate <60bpm, symptomatic bradycardia, signs of peripheral hypoperfusion, asthma/COPD, PR interval greater than 240ms
When are Implantable cardioverter-defibrillators (ICDs) used?
In patients with ischemic or non-ischemic cardiomyopathy and LVEF < 35%
provides significant survival benefit
What are the benefits of cardiac resynchronization?
Increased LV function
Increased Exercise capacity
Decreased heart failure exacerbation
Only indicated with patients with continued symptoms of heart failure while on maximum medical therapy, LVEF < 35%, prolonged QRS (>120 ms)
When are cardiac transplants indicated?
When all other medical treatments and managements have failed
How do you treat diastolic dysfunction?
Treat underlying condition - e.g. hypertension or pericardiectomy
Ionotropic agents are CONTRADICTED
Cautious use of diuretics for volume overload - stiff ventricles depend on high filling pressures to maintain cardiac output
What is the definition of a cardiomyopathy?
A structural or functional abnormality in the myocardium, independent of any other valvular, coronary, or myocardial involvement in systemic disease
What are the three main classifications of cardiomyopathies?
Dilated Cardiomyopathy (MC type): Features a reduced ejection fraction
Hypertrophic Cardiomyopathy: EF maintained, increased stiffness and diastolic dysfunction
Restrictive Cardiomyopathy: Infiltration by substances into myocardium marked by changes in compliance with preserved ejection fraction
What are the primary features of dilated cardiomyopathy (DCM)?
Cardiomegaly
Dilated ventricles
Impaired systolic function (decreased ejection fraction)
Increased myocardial mass
Increased predisposition to intra-cardiac thrombi
What is the etiology of dilated cardiomyopathy (DCM)?
Can basically be anything:
Idiopathic, familial, inflammatory (both infectious and non-infectious) toxic, metabolic, and neuromuscular
What is seen in the early stages of dilated cardiomyopathy (DCM)?
Tachycardia and inreased contractility to maintain cardiac output in light of a failure of the myocardium
What is seen in the later stages of dilated cardiomyopathy (DCM)?
Increased end-diastolic pressures along with decreased cardiac output.
This decreases renal perfusion which activates the R-A-A system to increase peripheral vascular resistance, further dilating all four chambers of the heart.
What are some symptoms of dilated cardiomyopathy (DCM)?
Dyspnea
Orthopnea
Paroxysmal Nocturnal Dyspnea
Weight gain
Edema
Decreased Exercise tolerance
Fatigue
Light-headedness
What are some physical findings (signs) of dilated cardiomyopathy (DCM)?
Cool extremities
Tachycardia
Displaced and diffuse apical impulse
Gallup rhythm
Rales
Signs of RV failure including JVD, hepatomegaly, edema, ascites
What do you see on chest x-ray in cases of dilated cardiomyopathy?
Cardiomegaly
Signs of heart failure including pulmonary vascular redistribution, interstitial and alveolar edema, pleural effusion
What do you see on EKG in cases of dilated cardiomyopathy?
Nothing specific, but may reveal a variety of abnormalities:
Chamber enlargement
Arrhythmias
Localized Q waves, dense fibrosis
Diffused ST, T wave abnormalities
What do you find on Echo in cases of dilated cardiomyopathies?
Chamber dilatation
Decreased ejection fraction (can be quantified here)
Presence or absence of intracardiac thrombus
Potentially concomitant valvular disease
Can be used to track pt progress
Why would you perform cardiac catheterization on a patient with dilated cardiomyopathy?
Useful to exclude coronary artery disease, valvular disease
Can perform a biopsy to confirm diagnosis of myocarditis
How do you treat dilated cardiomyoptahties (DCMs)?
Manage symptoms - medical treatment for systolic heart failure
Prevent complications such as arrhythmias or thromboembolic events
Prolong long term survival
Cardiac transplants
What is the prognosis for dilated cardiomyopathy patients?
1/3 will improve spontaneously
2/3 will have 5 year mortality of < 50% without cardiac transplant
What causes hypertrophic cardiomyopathy (HCM)?
Asymmetric hypertrophy of LV septum (not caused by chronic presure overload)
Inheritance is commonly autosomal dominant
What is seen on pathology of hypertrophic cardiomyopathy (HCM)?
Asymmetric LV septal hypertrophy
Disorganization of myocardial fibers in septum
What type of cardiomyopathy is suggested by asymmetric LV septal hypertrophy and findings of disorganized myocardial fibers in the septum?
Hypertrophic cardiomyopathy (HCM)
What are two different classes of hypertrophic cardiomyopathies?
HCMs with and wihtout outflow tract obstruction
What are some clinical symptoms of hypertrophic cardiomyopathy (HCM)?
Dyspnea
Angina
Syncope
Sudden cardiac death
What are some findings on exam (signs) of hypertrophic cardiomyopathy (HCM)?
Arterial pulse is abrupt and ill-sustained
S4 sounds
Double apical impuse
Signs of mitral regurgitation
Systolic murmor of HCM is distinct: crescendo and decrescendo at the lower left sternal border - increased with valsalva and standing, decreased with squatting
The obstruction is dynamic (increased afterload decreases obstuction; decreased afterload increases obstruction)
What do you find on chest x-ray in cases of hypertrophic cardiomyopathy (HCM)?
Nothing specific for HCM
What do you find on EKG in cases of hypertrophic cardiomyopathy (HCM)?
Left ventricular hypertrophy
LA enlargement
Q-wave and T-wave inversion
Arrhythmias
What do you find on echo on patients with hypertrophic cardiomyopathy?
Assymmetrical hypertrophy of the LV septum
Systolic anterior motion of the mitral valve
Intracavitary and subaortic pressure gradient
When do you perform cardiac catheteriation on patients suspicious for hypertrophic cardiomyopathy?
If the diagnosis is uncertain… This is usually not required
How do you treat hypertrophic cardiomyopathy (HCM)?
Beta blockers - negative inotropy (decrease oxygen demand, decrease LV outflow gradient during exercise, increase passive diastolic ventricular filling time, decrease frequency of ventricular ectopic beats)
Calcium channel blockers (instead of beta blockers)
Diuretics (in overt congestive heart failure)
Amiodarone (to treat arrhytmias)
ICD - family history of sudden cardiac death, ventricular wall greater than 30 mm, unexplained syncopal episodes, hx of tachyarrhytmia
Pacemakers
Surgical myomectomy
Percutaneous Septal Ablation
**** Avoid vasodilators, digitoxin****
How do beta blockers help in the treatment of hypertrophic cardiomyopathy (HCM)?
Decrease mocardial oxygen demand
Decrease LV outflow gradient during exercise
Increase passive diastolic ventricular filling time
Decrease frequency of ventricular ectopic beats
What is the natural history of hypertrophic cardiomyopathy?
Variable
Ranges from long life with few symptoms to rapid course with sudden death
When does sudden death occur in hypertrophic cardiomyopathy (HCM)?
When there are associated arrhythmias present
Which cardiomyopathy subtype is the least common?
Restrictive cardiomyopathy (dilated cardiomyopathy and hypertrophic cardiomopathy are more common)
What occurs in restrictive cardiomyopathy?
Diastolic dysfunction with preserved systolic function
Rigid myocardium - fibrotic or infiltrated
With end stage disease, the ventricular cavity may become obliterated
Cause of death at end stage is congestive heart failure
What is the etiology of restrictive cardiomyopathy (RCM)?
- *Non-infiltrative** (idopathic, scleroderma)
- *Infiltrative** (amyloid, sarcoid)
Storage diseases (Hemochromatosis, glycogen storage disease)
Endomyocardial diseases (endomyocardial fibrosis, hypereosinophilic syndrome)
Metastatic tumors
Radiation therapy
What is tropical endomyocardial firosis?
Unknown cause - seems to be related to troical environment
Disease in which firosis of ventricles occurs along with eosinophilia
Diastolic dysfunction and eventual obliteration of the left ventricle occur, and patients die by congestive heart failure
Treatments are often unsatisfactory, and surgeries (resections of oblierated tissue and valve repair) may only help in the short term
What is cardiac amyloidosis?
Primary: deposition of the Ig light chain (AL) fragments secreted by a plasma cell tumor (e.g. multiple myeloma)
Secondary: seen in variety of inflammatory conditions (Rheum. Arthr.)
Hereditary is autosomal dominant
Senile amyloidosis
In all: amyloid deposition is extracellular (between myocardial fibers, in the coronary arteries, veins and valves)
What are the different types of cardiac amyloidosis?
Primary: depositions of Ig light chain fragments secreted by plasma cell tumor
Secondary (to inflammatory condition, i.e. Rheumatoid Arthritis)
Hereditary (autosomal dominant)
Senile
What is the pathophysiology of restrictive cardiomyopathy (RCM)?
Rigid myocardium results in decreased ventricular filling (decerased cardiac output) and increased diastolic ventricular pressure (venous congestion)
As a result, you get symptoms of congestive heart failure (JVD< hepatomegaly, ascites, peripheral edema); and of decreased cardiac output (weakness, fatigue)
What are some clinical symptoms of restrictive cardiomyopathy (RCM)?
Dyspnea
Orthopnea
Paroxysmal Nocturnal Dyspnea
Weight gain
Decreased exercise tolerance
Edema
Fatigue
Light-headedness
What are some clinical exam findings (signs) of restrictive cardiomyopathy (RCM)?
Tachycardia
Rales
Kussmaul sign (Increased JVD with inspiration)
Other signs/symptoms of RV failure (JVD, hepatomegaly, edema, ascites)
What would a chest x-ray reveal for a patient with restrictive cardiomyopathy (RCM)?
Normal sized heart with signs of pulmonary congestion
What would an EKG reveal for a patient with restrictive cardiomyopathy (RCM)?
Non-specific ST-T changes, arrhytmias
What diagnostic test can you perform to differentiate a restrictive cardiomyopathy (RCM) from a constrictive pericarditis?
Cardiac CT or MRI
What is the treatment for restrictive cardiomyopathy?
There is a poor prognosis because treatment is mostly focused on treating the cause of the disease and symptoms; and often the causes are difficult to treat
Which cardiomyopathy is the most common?
Dilated cardiomyopathy (~90% of all cases)
What is the most common age of onset for dilated cardiomyopathy?
In males between 20 and 50 years old
What are findings on pathology of dilated cardiomyopathy?
Enlarged, flabby heart with dilatation of all chambers
Thin ventricles
Mural thrombi due to stasis
Absent valvular and vascular lesions that would cause secondary cardiac dilation
What are histological findings of dilated cardiomyopathy?
Non-specific, including:
Hypertrophied myocytes with enlarged, boxcar nuclei
Irregular myocytes with varying degrees of interstitial and endocardial fibrosis
What are common infectious causes of dilated cardiomyopathy?
Viral - Coxsackie, adenovirus, HIV, hep C, parvovirus
Parasitic - Trypanosoma cruzi (Chagas’ disease)
Bacteria - diptheria
Spirochete - Lyme disease (Boriella burgodrferi)
Rickettsial (Q fever)
Fungal (systemic)
What can clue you in to a viral etiology of dilated cardiomyopathy?
Lymphocyte aggregates with myocyte necrosis
What can clue you in to a fungal etiology of dilated cardiomyopathy?
Presence of hyphae on silver stain
What are non-infectous causes of dilated cardiomyopathy?
Granulomatous inflammatory disease (giant cell myocarditis, sarcoidosis)
Hypersensitivity (to antibiotics, sulfonamides)
Collagen vascular disease (polymyositis, dermatomyositis)
What histological features can identify giant cell myocarditis as the cause of dilated cardiomyopathy?
Multinucleated giant cells, interstitial infiltrate and myocyte necrosis
What are some drugs/toxins that can cause dilated cardiomyopathy?
Alcohol
Cocaine, emetine, anabolic steroids
Chemotherapy agents (anthracyclines, trastuzumab, IFN)
Other (hydroxychloroquine, chloroquine)
Heavy metals (lead, mercury)
Occupational (hydrocarbons, arsenicals)
What are the mechanisms of alcohol-related dilated cardiomyopathy?
Direct toxic effect of alcohol and its metabolites (acetaldehyde)
Secondary nutritional deficiency (thiamine)
Alcohol additives (cobalt)
What are some metabolic causes of dilated cardiomyopathy?
Nutritinal deficiencies (thiamine, selenium, carnitine)
Electrolyte deficiencies (calcium, phosphate, magnesium)
Endocrinopathy (thyroid, diabetes, …)
Obesity
Hemochromatosis (iron storage disorder)
What are some histological findings that can identify hemochromatosis as the cause of dilated cardiomyopathy?
Brown cytoplasmic iron pigments or a specific stain for iron
What is the most important cause of suddenc ardiac death in the young and in atheletes?
Hypertrophic Cardiomyopathy (HCM)
What are some causes of hypertrophic cardiomyopathy?
Genetic: genes encoding sarcomeric proteins (beta myosin heavy chain, for example)
What is the inheritance pattern of genetic hypertrophic cardiomyopathy?
Autosomal dominant with nearly complete penetrance
What are pathological features of the hypertrophy in hypertrophic cardiomyopathy?
Hypertrophy is asymmetric and confined to interventricular septum below the aortic valve in majority of patients
The interventricular septum is more hypertrophied than the free LV wall
What is a difference on gross pathology between hypertrophic cardiomyopathy and hypertrophy from hypertension?
HCM causes a disproportionate hypertrophy of the interventricular septum as opposed to the free LV wall
What are some microscopic/histologic freatures of hypertrophic cardiomyopathy?
Interstitial fibrosis and enlarged, box-car nuclei of the myocardial cells
Which cardiomyopathy is the least common?
Restrictive Cardiomyopathy (RCM)
What is the etiology of restrictive cardiomyopathy?
Primary: Tropical endomyocardial fibrosis - idiopathic
Secondary: infiltrative (amyloid, sarcoid, storage disorders), non-infiltrative (carcinoid, iatrogenic - i.e. due to radiation or chemo)
What is the gross appearance of a heart in restrictive cardiomyopathy?
Ventricles are of approximately normal size or slightly enlarged
Myocardium is firm and of normal thickness
There is bilateral dilation due to poor ventricular filling and pressure overloads.
What is Loeffler’s Endomyocarditis?
Restrictive cardiomyopathy that affects males in temperate climates
It results in death within months and can be identified on histology by an increased presence of eosinophils.
How do you identify amyloid when you suspect it to be the cause of restrictive cardiomyopathy?
Polarized congo red stain - you can see apple green birefringence
What is arrhythmogenic right ventricular cardiomyopathy (ARVC)?
A rare disease that is heritable and caused by mutations in desmosomal proteins (desmoplakin, plakophilin, desmoglein, desmocollin, plakoglobin)
Autosomal dominant, incomplete penetrance
Affects the right ventricle
Early phase is often clinically silent
Late phase predisposes to a disproportionate risk of arrhythmic events
What mutations are seen in arrhythmogenic right ventricular cardiomyopathy (ARVC)?
Mutations in desmosomal proteins
What is the inheritance pattern of arrythmogenic right ventricular cardiomyopathy?
Autosomal dominant
What do you see pathologically in arrhythmogenic right ventricular cardiomyopathy (ARVC)?
fatty and fibrofatty replacement of heart muscle
What is isolated left ventricular noncompaction (LVNC)?
Congenital myocardial disorder that is a common cause of cardiomyopathy in children
Presents with congestive heart failure, arrhythmia, or complications of thromboembolism
Persistence of the noncompacted endocardial layer is characteristic of the early fetal period before myocardial compaction is complete
Left ventricle is dilated or hypertrophied
What do you find on pathology in cases of isolated left ventricular noncompaction (LVNC)?
Complex meshwork of trabeculations and recesses
Sponge-like appearance of the LV wall
Abnormal myocardial hypoperfusion
What cells maintain the integrity and elasticity of arterial vasculature?
Endothelial cells and smooth muscle cells
What are some key characteristics of endothelial cells?
Impermeable to large molecules (LDL-C)
Anti-inflammatory
Promote vasodilation
Resist thrombosis
What are some important characteristics of smooth muscle cells?
Effect vasoconstriction/dilation in response to local or circulating molecules (provide tone)
Produce extracellular matrix that maintains vascular integrity (collagen provides strength; elastin provides flexibility)
They are contained within the arterial tunica media
Where are smooth muscle cells of the vasculature located?
In the tunica media of arteries
What is significant about a fatty streak?
It is a hallmark of early atherogenesis, and allows the entry of lipoprotein particles (LDL) into the sub-intimal space
This causes a recruitment of immunologic mediators (inflammation)
LDL is modified (oxidation or glycation)
mLDL is taken up by monocytes (foam cells), and these cells undergo necrosis
These lesions are apparent in healthy individuals by late teens
What is a foam cell?
A monocyte that has taken up mLDL from an arterial subinimal space
This is generally unregulated
These cells gorge themselves on LDL and become the necrotic core of an atherosclerotic lesion
What occurs during plaque progression of atherosclerosis?
Smooth muscle cells migrate to the sub-intimal space where they’re not supposed to be.
Smooth muscle cells proliferate and secrete extracellular matrix, producing the fibrous cap of the plaque.
This usually occurs outwardly and preserves the luminal diameter
Later on, this will occlude the vessel
What distinguishes a vulnerable plaque from a stable plaque?
What are characteristics of vulnerable atherosclerotic plaques?
What are characteristics of stable atherosclerotic plaques?
What occurs in atherosclerotic plaque disruption?
Fibrous cap ruptures as a consequence of hemodynamic stress and matrix degradation.
This is the most common mechanism for atherosclerotic-induced MI
This is a thrombogenic event, which causes a fibrin, red cell and platelet thrombus to form on top
Not all ruptures manifest clinically
What are likely manifestations of atherosclerosis?
Ischemic stroke or transient ischemic attack
Myocardial infarction, angina, sudden death
Intermittent claudication, critical limb ischemia, gangrene, necrosis
Recall, atherosclerosis is a SYSTEMIC disease that manifests locally
What are some risk factors for atherosclerosis?
- *Traditional:**
- Non-modifiable - *Age, Gender, Genetics;
*Modifiable - *Dyslipidemia, Smoking, Diabetes, Phisical Inactivity
Non-traditional:
Apolipoprotein (a)
C-reactive protein
Homocysteine
What relationship does cardiovascular disease have with age and sex?
Increases linearly with age
Risk is higher among men than in women in youth, but reverses with age.
What is the function of lipoprotein particles?
Transport cholesterol in serum
What is HDL-C?
High Density Lipoprotein Cholesterol
This is “Good” cholesterol
Acts as a reverse cholesterol transporter (takes from periphery and brings it back to the liver)
Why is HDL-C known as “good” cholesterol?
It participates in reverse cholesterol transport - takes cholesterol from the periphery to the liver
What is LDL-C?
Low Density Lipoprotein Cholesterol
“Bad Cholesterol” that deposits in the arterial wall leading to atherosclerosis
It is the primary target of pharmacotherapy
Why is LDL-C known as “bad” cholesterol?
It deposits in the arterial walls, leading to atherosclerosis
How can one lower LDL-C levels?
Diet/Exercise (Therapeutic Lifestyle Changes)
Pharmacologic therapy: Niacin; bile acid sequestrans; fibric acid; statins (HMG-CoA Reductase Inhibitors)
How do HMG-CoA Reductase Inhibitors (i.e. Statins) work?
Increase expression of LDL-C receptor in liver, thereby lowering serum levels of LDL-C
What are some benefits of statins?
Benefit is proportional to the degree of lowering of LDL-C
Also, you can see a modest elevation of HDL-C (this is good)
Also, favorably modulates vascular tone, stabilizes plaques, and reduces inflammation
What are some confounding factors that make it difficult to modulate LDL levels?
Cigarette smoking
Hypertension
Low HDL
Family history of coronary heart disease
Age
What are the LDL targets for individuals with coronary heart disease, 2+ risk factors, or 0-1 risk factors?
CHD: <100
2+ : <130
0-1 : <160
Is it a viable strategy to attempt to raise HDL-C levels?
Not really - many attempts have not been succesful or proven. Many have poor side effects
Best bet is to use non-pharmacologic methods (diet + exercise)
What are some cardiovascular effects of diabetes mellitus?
Enhanced inflammation
Increased platelet reactivity, hypercoagulability
Endothelial dysfunction
Nonenzymatic glycation of lipoproteins
Vascular stiffness and arterial calcification
Sum total is ACCELERATED atherosclerosis in a genearlly PROthrombotic state
What is meant by the statement that diabetes is a coronary heart disease “risk equivalent”?
It means that the risk for coronary heart disease among people with diabetes and no prior MI is equal to those who do not have diabetes but have had a prior MI
What are good treatment strategies for the mitigation of the risk of cardiovascular disease in diabetic patients?
Glycemic control is key
But often times that is not enough - need to also aggressively control modifiable cardiac risk factors (hypertension, hyperlipidemia, obesity)
What are some vascular effects of obesity/physical inactivity?
Inflammation - adipose tissue can secrete pro-inflammatory cytokines
Hypertension - increased cardiac output to meet increased metabolic demands of excess body weight + changes in vascular tone
Endothelial dysfunction
Insulin resistance - leading to diabetes
How is BMI measured?
weight in kg/ (height in meters)^2
What is the normal range of BMI?
18.5-24.9
What defines obesity?
BMI over 30
What is the relationship between BMI and mortality in US adults?
High mortality at both ends of BMI scale
Lower BMI mortality may be attributable to malnourishment, or frailty
How is smoking a risk factor for coronary heart disease?
Smoking is associated with excess of fatty streaks and raised lesions in abdominal aorta
Causes endothelial damage
Exerts prothrombotic effects on platelet function
Causes coronary vasoconstriction
Produces oxidative modification of LDL-C
What is homocysteine?
A biomarker of atherogenesis that may be linked to the pathophysiology of arteriosclerosis via oxidative stress, inflammation and platelet aggregation
Reduction of homocysteine does not correlate with reductions of cardiovascular risk
What is lipoprotein (a)?
A variant of LDL that contains apolipoprotein apo(a)
May impair endogenous thrombolysis and promote inflammation
Higher Lp(a) levels correlate with higher risk for CV events, but therapeutic benefits are unclear
What is C-Reactive Protein?
Acute phase reactant released by liver that is a good marker of inflammation
Has been associated with increased cardiac risk independent of cholesterol levels, but it is still unclear if CRP is a marker or mediator of atherosclerosis
How do you diagnose hypertension?
Two independent readings with the patient not ingesting caffeine or smoking 30 minutes prior to measurements
Patient sitting for 5 minutes
What are four determinants of blood pressure regulation?
Heart - provides cardiac output
Peripheral vasculature - vascular tone/resistance
Kidney - regulates intravascular volume, and is essential in the maintenence of chronic hypertensive states
Hormones/Reflexes - modulates all systems simultaneously
What is an equation that represents blood pressure?
BP = Cardiac output * Total peripheral resistance
What are the determinants of cardiac output?
Cardiac output = Heart rate * stroke volume
What are two determinants of stroke volume?
contractility and venous return
What are determinants of venous return?
blood volume and venous tone
How do the kidneys regulate blood pressure?
Renin-Angiotensin-Aldosterone system
What is pressure natriuresis?
Simple hemodynamics - more pressure = more in, increases GFR, increases Na and H20 excretion
Doesn’t involve sensors or circulating factors
In chronic hypertension, this is blunted… requires greater blood pressure to excrete a given salt load
What role do baroreceptors play in blood pressure and its regulation?
Moment-to-moment regulation of BP
Found in aortic arch and carotid sinuses
Reflex response that works relatively instantaneously
What is essential hypertension?
Elevation in BP without a readily identifiable cause
It is a syndrome rather than a disease with clear etiology
MOST COMMON form of HTN (~90%)
Diagnosis of exclusion - first need to rule out other potential causes that would secondarily produce hypertension
What are some causes of essential hypertension?
Genetics - still unclear
Systemic abnormalities - vascular tone or sympathetic overactivity
Renal abnormalities - excess Na/H20 retention, or horomonal dysregulation (high baseline renin levels, for example)
In younter patients, is essential hypertension usually systolic or diastolic?
Diastolic
In older patients, is essential hypertension usually systolic or diastolic?
systolic
What is secondary hypertension?
Hypertension in the setting of a clear structural/hormonal cause
Treatment may be curative
What are clinical clues to a diagnosis of secondary hypertension?
Very young, or new hypertension after age 50
More severe with rapid onset
Physical signs/symptoms of renal disease, stenosis
How can renal disease cause secondary hypertension?
Impaired ability of kidneys to excrete sodium/water causes a rise in intravascular volume which results in elevated cardiac output and blood pressure
What are some laboratory findings that can identify renal causes of secondary hypertension?
Elevated serum creatinine, abnormal urinalysis
What are renovascular causes of secondary hypertension?
Renal artery stenosis - atherosclerosis (in 2/3 of cases) or fibromuscular dysplasia (in 1/3 of cases, mostly in young women)
Stenosis causes reduced renal blood flow, which induces renin secretion and increased Angiotensin II (causing vasoconstriction) and increased aldosterone (causing sodium retention)
You can hear an abdominal bruit and you see an unexplained hypkalemia
Why do you see hypokalemia in renovascular causes of secondary hypertension?
In these patients you have increased aldosterone which increases sodium retention (at the expense of potassium - Na/K pump)
What are treatments for secondary hypertension due to renovascular causes?
Renal artery revascularization
ACE inhibitors
How can aortic coarctation cause secondary hypertension?
Narrowing of aorta causes reduced blood flow to kidneys which stimulates RAAS and increases angiotensin II causing vasoconstriction
You can see BP discrepancy - arms vs legs and left vs right arm in some cases
What are some endocrine causes of secondary hypertension?
Catecholamine-secreting tumors of neurendocrine cells in the adrenal medulla
Or excess mineralocorticoid secretion (aldosterone)
Or excess glucocorticoid secretion (cortisol)
How do catecholamine-secreting tumors of neuroendocrine cells cause secondary hypertension?
Release epi/norepi - causes vasoconstriction/tachycardia that can come in waves
How does excess mineralocorticoid secretion cause secondary hypertension?
Excess aldosterone - RAAS system activated
What is Conn Syndrome?
Primary aldosteronism - causes secondary hypertension
How does excess glucocorticoids cause secondary hypertension?
Cortisol - expands blood volume, stimulates RAAS
What is Cushing Syndrome?
Excess cortisol - rounded facial appearance, central obesity, muscle weakness and hypertension
How does hyperthyroidism cause hypertension?
Cardiac hyperactivity - increase in blood volume
How does hypothyroidism cause hypertension?
Diastolic hypertensoin due to increase in peripheral vascular resistance
What can be a cardiovascular side effect of oral contraceptives?
Hypertension - estrogen increases synthesis of angiotensinogen (RAAS)
What are some drug-related causes of hypertension
Oral contraceptives
Glucocorticoids
Erythropoetin
Sympathomimetics (OTC cold remedies)
Alcohol
Cocaine
What are some consequences of hypertension?
Physiologic/structural derangements that manifest chronically:
Increased workload of heart
Arterial damage (smooth muscle cell hypertrophy, endothelial dysfunction, loss of elasticity)
Organ damage (heart, cerebral vasculature, aorta, kidney, retina)
What are cardiac effects of hypertension?
Ventricular hypertrophy - leads to ventricular stiffness and diastolic dysfunction
Systolic dysfunction (due to potential myocardial ischemia)
Coronary Artery Disease - HTN promotes development of atherosclerosis which decreases myocardial oxygen supply; alos, increased cardiac work due to elevated BP causes increased myocardial oxygen demand
What are some cerebrovascular effects of hypertenison?
HTN is one of the strongest risk factors for stroke
Hemmorrhagic - rupture of microaneurysms
Ischemic - thrombosis due to atherosclerotic plaques and subsequent embolism
Treatment of BP reduces stroke-related deaths by 50%
What are some aorta-related complications of hypertension?
Aneurysm - abdominal aorta below renal arteries
Dissection of ascending and descending, due to intimal tears - high mortality
What is hypertensive crisis?
Urgency - BP > 180/110 with no end-organ damage; does not require hospitilization
Emergency - BP > 180/110 with signs of end-organ damage; Requires hospitalization
End organ damage can be hypertensive encephalopathy, dyspnea, eye damage
What differentiates a hypertensive urgency from a hypertensive emergency?
In both cases, SBP > 180 or DBP > 110, but in emergency there is sign of end-organ damage whereas in urgency there is not
What are components of a history/physical exam that can help identify hypertension?
Weight gain/loss, renal damage (history of UTIs)
Lifestyle behaviors such as alcohol or drugs
Medicaiton history of prescription and OTC
Murmurs, bruits, or BP discrepancies
What are some laboratory findings that may be helpful in identifying hypertension?
Renal abnormalities (creatinine, urine analysis)
Serum potassium (hypokalemia may clue to increaed aldosterone)
Blood glucose
What evidence of hypertension can be seen on electrocardiogram?
Evidence of LV hypertrophy
What are some non-pharmacologic treatments of hypertension?
Weight reduction, exercise, diet modification, salt restriction, smoking/drinking cessasition
What are some pharmacologic therapies for hypertension?
Diuretics (chepa, and ideal choice for management of uncomplicated hypertension)
Sympatholytic agents (Beta blockers) - reduce cardiac output and decrease renin secretion => Side effects include asthma, fatigue, and impotence
Why do alpha-2 adrenergic agonists help in the treatment of hypertension?
Reduce sympathetic outlow
However, have a poor side effect profile and are rarely used
Why are alpha-1 antagonists useful in treating hypertension?
Relax vascular smooth muscle and also have added benefit of reducing prostatic enlargement in older men
What is the effect of calcium blockers in treating hypertension?
Reduce influx of calcium necessary for cardiac/vascular smooth muscle contraction - reduces contractility and resistance
(peripheral vasodilator)
How do ACE inhibitors work in the treatment of hypertension?
Block conversion of angiotensin I to angiotensin II and block RAAS
Reduce mortality in high-risk cardiac patients
Side effects include dry cough and hyperkalemia
What are some side effects of ACE inhibitors?
Dry cough, hyperkalemia
What are ARBs?
Angiotensin-II receptor blockers
What is the first line agent for uncomplicated hypertension?
Thiazide diuretics
Have proven benefits and low cost with an acceptable safety profile
How do you choose a anti-hypertensive drug for a patient with complicated hypertension?
Consider co-morbidities and try to kill two birds with one stone:
E.g. avoid ACE inhibitors in women with child-bearing age (teratogenic)
Avoid diuretics in elderly - dehydration
What effect does the rate of blood flow have on the development of thrombi?
In areas of high shear stress, endothelial cells generate an anti-thrombotic state
In slow-flow areas, the arterial walls are thickend and there is decreased luminal size
What is the effect of endothelial derived relaxing factor (EDRF, a.k.a. NO) on the vasculature?
Inhibits smooth muscle contraction and proliferation
Inhibits platelet aggregation
Inhibits LDL oxidation
Decreases expression of adhesion molecules
Decreases endothelin production
What is endothelin?
A factor produced by endothelial cells of the vasculature that promotes vasoconstriction and coagulation
What is the role of endothelium in atherothrombosis?
Endothelium produces both pro- and anti- atherogenic substances:
Pro: vasoconstrictors, prothrombotics, pro-inflammatories, smooth muscle cell promoters
Anti: vasodilators, antithrombotics, anti-inflammatories, smooth muscle cell inhibitors
What event causes platelet aggregation in the vasculature?
Release of NO (due to injury or other endothelial dysfunction)
This causes platelet adhesion and subsequent thrombus formation
What is the difference between atherosclerosis and atherothrombosis?
People generally lives with atherosclerosis, but people die from atherothrombosis…
What function does aspirin have on atherothrombotic disease?
Inhibits Arachidonic Acid pathway viea acetylation of Cyclogenase enzymes (COX1 and COX2)
Inhibits platelet aggregation and is an effective, safe, and inexpensive antithrombotic agent
What is the efficacy of P2Y12 inhibitors vs aspirin?
More effective and efficacious in ASA-resistant patients
e.g. clopidogrel, prasugrel, ticagrelor
What is clopidogrel?
ADP receptor inhibitor - blocks platelet activation
Used as antithrombotic therapy - in patients who are ASA intolerant
What are diferent forms of pericardial disease?
Acute pericarditis
Pericardial effusion +/- cardiac tamponade
Constrictive pericarditis
What are some causes of acute pericarditis?
Infectious: viral are most common (coxsackie and echovirus), but the least commonly identified; often labeled as idiopathic
Bacterial in the case of pneumonias
TB with immigrants
Non-infectious: Post MI, metabolic disorders, surgery, trauma, radiation, drugs, malignancies, collagen vascular disease
What determines how much pericardial involvement there will be following an MI?
Infarct size
What is the mechanism of pericarditis following an MI?
Early - inflammatory
Late stages - immune mediated (weeks to months later). This is autoimmune
Known as Post Cardiac Injury sydnrome or Dressler’s Syndrome
What is Dressler’s Syndrome?
Post-MI autoimmune-mediated pericarditis
What are some symptoms of acute pericarditis?
Chest pain (retrosternal, pleuritic - i.e. on breathing, positional - e.g. when leanign forward)
Dyspnea (because of pain on breathing)
Fever
What are some signs of acute pericarditis?
Pericardial friction rub (ejection, early diastole, late diastole). This is best heard in expiration in a seated position
This is highly specific for pericarditis
What tests would you order when suspecting pericarditis?
CBC
Bacterial culture if febrile
EKG - check for ST elevation or PR depression
CXR
Echo
What findings do you find on EKG in acute pericarditis?
ST elevation in most leads (evidence of injury)
Depression of PR segment
Low voltage QRS
T wave inversion
What is suggested by this EKG?
Acute pericarditis
What is the treatment for acute pericarditis?
Bed rest
NSAIDs
Colchicine for the prevention of recurrent pericarditis (potent anti-inflammatory)
Steroids (only if recurring)
Treat for underlying etiology
What are some complications of acute pericarditis?
Constriction - scarring and loss of elasticity of the pericardial sac
Tamponade - accumulation of pericardial fluid under pressure
Recurrent pericarditis (autoimmune role suspected)
What can cause pericardial effusions?
Infections (viral, bacterial, TB)
Non-infectious - Malignancy, renal failure, hypothyroidism, radiation, trauma, aneurysim, AIDS
What is a significant contraindiction in the treatment of pericardial effusions?
DO NOT DRAIN - take to the OR. Draining can cause patients to bleed out
What are some symptoms of pericardial effusions?
Can be asymptomatic
Dyspnea
Cough
Dysphagia
Hiccup
Hoarseness
Abdominal fullness
What are some signs of pericardial effusions?
Muffled heart sounds
Decreased intensity of heart sounds
What is the appearance of pericardial effusion on x-ray?
Water-bottle heart
What is this x-ray suggestive of?
Pericardial effusion
What is cardiac tamponade?
A clinical syndrome of hypotension, tachycardia, and associated symptoms that occurs when intrapericardial pressure exceeds intracardiac pressure
What is the difference between slowly and rapidly developing pericardial effusions with tamponade?
Slowly - pericardium can stretch and the tamponade occurs with a larger volume
Rapid - pericardium has no time to stretch and the tamponade occurs with a smaller volume
How ist he pathophysiology of tamponade dependent on breathing?
Similar to constriciton
On inspiration, RV volume is greater than LV, on expiration, it is the opposite.
This is an exaggerated interventricular dependence
What are some clinical symptoms of cardiac tamponade?
Dyspnea
Orthopnea
Fatigue
What are some clinical signs of cardiac tamponade?
Tachycardia
Pulsus paradoxus
Increased JVP
Decreased Systolic BP with narrow pulse pressure
Muffled heart sounds
Dullness to percussion (Ewart’s Sign)
Kussmaul’s Sign (visible neck veins on inspiration)
Beck’s Triad - decreased arterial pressure, increased venous pressure, distant heart sounds
What is Beck’s Triad?
Decreased arterial pressure
Increased venous pressure
Distant heart sounds
What is Ewart’s Sign?
Dullness to percussion in left lung (collapse) in the context of cardiac tamponade
What is Kussmaul’s Sign?
Visibility of neck veins on inspiration
What are some characteristics of an EKG in the event of a cardiac tamponade?
Swigning heart - changes in electrical amplitude
What is the treatment of cardiac tamponade?
Pericardiocentesis (drain it)
IV fluids and pressor agents
What is constrictive pericarditis?
Pericarditis brought about by changes in the material properties of the pericardium
What are some issues that arise with constrictive pericarditis?
Diastolic heart failure (ejection is maintained) due to non-elastic, thick pericardium. The myocardium is usually fine.
Symptoms include exertional dyspnea and the right side of teh heart is affected more than left - congestive heart failure
What can cause constrictive pericarditis?
Heart surgery, radiation, idiopathic, connective tissue disease, infection, malignancy
What are some clinical symptoms of constrictive pericarditis?
Dyspnea
Fatigue
Weight gain
Chronic edema
What are some clinical signs of constrictive pericarditis?
Tachycardia
Hypotension
Elevated JVP
Kussmaul’s Sign
Pericardial Knock
Edema
Ascitis, hepatomegaly
Can look like jaundice
“sounds like a liver case, but looks like a heart case”
What are some findings you might see on EKG in cases of constrictive pericarditis?
In chronic cases - atrial fibrillation
What is somethign you might find on chest x-ray in a case of constrictive pericarditis?
Calcified pericardium
What is suggested in this chest x-ray?
Calcified pericardium - constrictive pericarditis
What is the most common source of prolonged A-V conduction?
Delays in the AV node
When might you normally have prolonged AV conduction?
When you sleep - high vagal tone
When might you normally have shorter AV conduction?
When you run - high sympathetic tone
What can shorten AV conduction?
Sympathetic tone
What is the effect of sympathetic tone on AV conduction?
Shortens
What is the rule in classifying 1st, 2nd, and 3rd degree AV blocks?
1, 2, 3 correspond to all, some, or none with regards to QRSs conducted following P
e.g. some p result in QRS, but not all = 2nd degree AV block
What is a 1st degree AV block?
prolonged, constant PR interval (longer than 200 ms) but every P has a QRS that follows
no real threat of sudden death
What are some causes of first degree heart block?
High vagal tone (atheletes)
Medications (beta blockers, calcium channel blockers)
Aortic sclerosis
What are some symptoms of first degree heart block?
Usually none, unless there is a severely prolonged PR interval
What is the treatment for a first degree heart block?
usually none
What are the three types of second degree heart block?
Mobitz 1 - progressive PR prolongation until dropped QRS
Mobitz 2 - sudden failure of conduction (and missed QRS)
2:1 conduction - something in between (every 2 P = 1 QRS)
What characterizes a second degree heart block, Mobitz Type I?
Progressively longer PR intervals until you drop a beat
What causes a Mobitz Type I second degree heart block?
High vagal tone (atheletes)
Medications (beta blockers, calcium channel blockers)
Aortic sclerosis/stenosis
What are some symptoms of a second degree heart block, Mobitz type I?
Usually none, aside from a sensation of skipped beats
What is the treatment for a second degree heart block, Mobitz type I?
Usually none
Where is the level of block in a second degree block, Mobitz type I?
usually at AV node
There is no real threat of sudden death
What is a second degree heart block, Mobitz Type II?
Sudden failure of conduction
What are the causes of a second degree heart block, Mobitz Type II?
Medication toxicity (digitoxin)
Myocardial infarction
Lyme disease
Advanced conduction system disease
What are some symptoms of a second degree heart block, Mobitz Type II?
Dizziness/syncope - but may be asymptomatic
predominantly asymptomatic
What is the treatment for a second degree heart block, Mobitz Type II?
Pacemaker - this is a potentially life threatening condition and requires intervention
Where in the conduction system is there a defect in a second degree heart block, Mobitz Type II?
Usually below the AV node, in the His-Purkinje system; Makes this a very dangerous condition with risk of sudden death
What is a second degree heart block 2:1 AV conduction?
Condition where there is a 2:1 P:QRS ratio
Cannot be classified as either Mobitz 1 or Mobitz 2
What is a third degree heart block?
A.k.a. complete heart block
P waves and QRS waves are dissociated
Atria and ventricles are not communicating and each are doing their own thing
What type of heart block is seen in this EKG?
2nd Degree AVB - Mobitz II
no change in PR interval and some QRS are dropped
What type of heart block is seen in this EKG?
2nd degree, Mobitz I
QRS are grouped together. PR progressively gets longer
What type of heart block is seen in this EKG?
3rd degree - P and QRS are completely dissociated - no pattern
Where does the right bundle course through?
The right side of the interventricular septum
Describe the right bundle.
Long, thin, discrete structure that courses down the right side of the interventricular septum
What is the result of a Right bundle branch block (RBBB)?
Delayed activation of the RV
This is common in the general population and usually has no prognostic significance
What are diagnostic critera for a right bundle branch block?
QRS > 120
Broad, notched ‘secondary’ R waves in right precordial leads (Bunny ears)
Deep S waves in left precordial leads
Where does the left branch course through?
The membranous portion of the interventricular septum near the aortic ring and then divides into three discrete branches: left anterior, left posterior, and left median fascicle
What is significant about a left bundle branch block?
usually indicates underlying structural heart disease
Dramatically alters ventricular activation
Must work these patients up
Describe the left branch.
More diffuse than the right branch. Courses through the membranous portion of the interventricular septum near the aortic ring and then divides into 3 discrete branches: left anterior, left posterior, and left median fascicles
What are the diagnostic criteria for a left bundle branch block (LBBB)?
QRS > 120
Small or absent R waves in V1/V2 and deep S waves in V1/V2
Broad, notched monophasic R waves in V5/V6 and usually in leads I and aVL
What is indicated by the following EKG?
LBBB
What is indicated by the following EKG?
RBBB
What does stable ischemic heart disease reflect in terms of the metabolic state of myocardial tissue?
An imbalance between the oxygen supply and demand
What are the two components of myocardial oxygen supply?
Blood oxygen content (Hemoglobin level and oxygen saturation) - usually not the culprit
Coronary flow - more common culprit in coronary artery disease
What are some determinants of coronary flow?
Q = P/R (directly proportional to perfusion pressure; inversely proportional to vascular resistance)
What is the minimum diastolic pressure needed to ensure adequate flow to the coronary arteries?
60-65 mm Hg
When during the cardiac cycle does coronary flow occur?
Diastole
What are factors that affect coronary vascular resistance?
Vascular tone
Degree of coronary stenosis
What are mediators of vascular tone?
Metabolic - adenosine, lactate, acetate, hydrogen ions, CO2
Neural Factors - Alpha (vasoconstriction) and Beta-2 (vasodilation) adrenergic receptors
Endothelial Factors - NO, prostacyclin, EDHF (vasodilators) ; endothelin-1 (vasoconstrictor)
What is the most important metabolic mediator of vascular tone?
Adenosine
Produced during hypoxemia (during anaerobic work)
Binds to vascualr smooth muscle and causes vasodilation
When is adenosine produced in the context of mediating vascular tone?
During hypoxemia
Causes vasscular smooth muscles to dilate, increasing vascular flow
What is the effect of adenosine on vascular smooth muscle?
Vasodilation - causes increased coronary flow in coronary vessels
What mechanisms of response to neural factors do coronary vessels contain?
Alpha (vasoconstriction) and Beta-2 (vasodilation) receptors
Which neural factors cause vasoconstriction in the coronary arteries?
Alpha adrenergic receptors
What neural factors cause vasodilation in the coronary vessels?
Beta-2 adrenergic receptors
What are the endothelium-dependent vasodilators?
ACh, Serotonin, Shear stress
The endothelium produces NO, Prostacyclin, EDHF in response to these factors, and induces vascular smooth muscle relaxation
This results in vasodilation and increased blood flow
What are the endothelium-dependent vasoconstrictors?
Thrombin, Angiotensin II, epinephrine
These cause the endothelium to produce endothelin 1 and causes vascular smooth muscle cell contraction
This results in reduced blood flow
What does endothelium-dependence mean?
It means that a factor would not have the resulting effect if not for the presence of an in-tact endothelium
What factors cause endothelial cells to produce NO, prostacyclin, and EDHF?
ACH, serotonin, shear stress
In which direction (vasodilation/vasoconstriction) is the balance tilted towards in healthy states of coronary artery function?
Vasodilation
In which direction (vasodilation/vasoconstriction) is the balance tilted towards in unhealthy states of coronary artery function (i.e. endothelial dysfunction)?
Vasoconstriction
What is the effect of ACh on smooth muscle in the absence of normal endothelial function?
Vasoconstriction
What is the effect of ACh in the presence of normal endothelial function?
Vasodilation
ACh alone causes vasoconstriction
However, the effect of ACh on the endothelial cells is to cause nitric oxide production (NO), which promotes vasodilation
The net effect is vasodilation
Abnormal response to ACh can suggest endothelial dysfunction
What is suggested by a vasoconstriction response to ACh by vessel endothelium?
That there may be endothelial dysfunction
Normal function of ACh in the context of healthy endothelium is vasodilation
What are determinants of myocardial oxygen demand?
Ventricular wall stress - wall stress promotes hypertrophy as a compensatory mechanism - more oxygen demand
Heart Rate - increased HR requires more oxygen demand
Contractility - stronger contractions requrie more energy/oxygen
What is the relationship between heart rate and the oxygen demand of the myocardium?
Direct relationship - greater the heart rate, the more oxygen is required
What is the relationship between the contractility of the myocardium and its oxygen demand?
Direct - more contractility (stronger/greater contractions) requires more oxygen
What is the relationship between ventricular wall stress and the oxygen demand of the myocardium?
Pressure overload states increase wall stress
Volume overload states increase wall stress
Myocytes hypertrophy in response to increased wall stress; this requires more oxygen
What are the determinants of ventricular wall stress?
P = pressure
r = radius
h = wall thickness
Hypertrophy (increase in h) is a response to increases in pressure/volume
What is the effect of atherosclerotic plaques on the resistance to coronary blood flow?
Plaques increase resistance
The reduction in luminal diameter exerts a much greater effect on increasing resistance than does the length of the lesion:
where R = resistance
L = length
r = luminal radius
What level of stenosis is requried to impair maximal blood flow under conditions of stress?
70% occlusion
What level of stenosis is required to impair blood flow at rest?
up to 90%
What characterizes endothelial cell dysfunction?
Release of endothelium-dependent vasodilators (prostacyclin/NO) may be impaired in response to normal stimuli (e.g. shear stress)
Vasodilatory effects of local metabolites (e.g adenosine) may be blunted
Vasoconstricting effects of catecholamines (e.g. ACh) predominates
Loss of antithrombotic effect of endothelial cells in response to stimuli (e.g. ADP, serotonin, thromboxane), resulting in a pro-thrombotic state in the setting of plaque rupture
What are non-atherosclerotic causes of myocardial ischemia?
Reduced oxygen supply: aortic regurgitation (decrease in diastolic pressure reduces coronary artery perfusion), acute blood loss (GI bleeds)
Increased oxygen demand: tachyarrhythmias, acute rise in BP - increases stress and causes necrosis, severe aortic stenosis
What are some medical issues that may cause reduced oxygen supply to the myocardium?
Atherosclerotic lesions of the coronary arteries
Aortic regurgitation - decreases diastolic pressure and reduces perfusing pressure of coronary arteries
Acute blood loss - for instance, due to a GI bleed
What are some medical issues that may cause increased oxygen demand from the myocardium?
Tachyarrhythmias - like rapid atrial fibrillation
Acute rises in blood pressure - will cause increased wall stress and necrosis (hypertensive crisis)
Severe aortic stenosis
What are potenial effects of ischemia on the myocardium?
Myocyte necrosis - irreversible cell death
Stunned myocardium - temporary dysfunction with function gradually restoring
Hibernating myocardium - chronic dysfunction that can have restored function with revascularization
What is myocyte necrosis?
Sequella of ischemia that is marked by irreversible cell death in the context of a prolonged episode (infarct)
Can be detected by EKG (Q wave) and in cardiac imaging (akinetic, thinned wall on echo)
What are signs of myocyte necrosis on EKG and Echo?
EKG - Q wave abnormalities
Echo - akinetic, thinned ventricular wall
What is a stunned myocardium?
Temporary systolic dysfunction after an episode of transient ischemia - not necrosis
Magnitude depends on degree of insult
Function gradually recovers with therapy
What is a hibernating myocardium?
Chronic ventricular dysfunction due to multivessel coronary artery disease in the setting of reduced blood supply (e.g. diabetes)
Revascularization restores ventricular function
What defines a stable angina?
Retrosternal chest discomfort precipitated by exertion and relieved by rest
Usually occurs when stenosis is less than 70% of the lumenal size
Myocardial oxygen supply may be unable to meet the oxygen demands during exertion
This is reproducible
What defines unstable angina?
New-onset SEVERE angina or increase in the severity and/or frequency of previously stable symptoms
Often caused by plaque rupture which leads to thrombosis, reducing myocardial oxygen supply
What is variant angina?
Episodes of coronary spasm reduce oxygen supply
Occurs at rest while stable angina occurs with increased demand
May be caused by endothelial dysfunction or increased sympathetic activity
What is Syndrome X?
Chest pain wtih positive stress test, and normal coronary arteries
Pain is significant
May be caused by microvascular dysfunction, spasm, or abnormal pain perception
What is silent ischemia?
Ischemia without clinical symptoms
More common in Diabetes, women, and elderly
Do you treat? Trials ongoing to address this possibility
What is most important in attempting to diagnose chronic stable angina?
History!
Quality, duration, location, associated sy mptoms, precipitants, and frequency
How long does chronic stable angina usually last?
Usually a few minutes - pain lasting a few seconds is normally non-cardiac
How is the pain in chronic stable angina localized?
Usually diffuse rather than focal sensation
Can radiate to left arm/neck
What are symptoms associated with chronic stable angina?
Shortness of breath, fatigue, diaphoresis (sweating), nausea
What are some precipitating factors that can be present in chronic stable angina?
Activities that increase myocardial oxygen demand - physical exertion, emotional stress
Usually relieved with several minutes of ceasing the activity
What role does the physical exam play in diagnosing stable angina?
More of a screening for other non-coronary vascular diseases (peripheral vascular disease, aortic aneurysm, renovascular - i.e. bruits)
Has a limited role in diagnosis as symptoms occur with activity
What diagnostic tests can help in diagnosing chronic stable angina?
EKG
Stress Test with Echo or Nuclear Perfusion
What findings on EKG can help diagnose chronic stable angina?
ST segment depression and/or T wave inversions reflect myocardial ischemia
ST segment elevation reflects myocardial injury (infarction)
Can likely be completely normal (~50% of pts)
What are two components of stress tests?
Stress - pharmacologic or exercise
Ischemic detection - via EKG, nuclear perfusion imaging, ultrasound
Exercise is always preferred as it allows for the assessment of functional capacity
What is coronary angiography?
Invasive procedure requiring contrast media that allows for direct visualization of stenotic lesions
GOLD STANDARD in diagnosis of CAD
Drawback: can only visualize lesions that obstruct lumen; unable to asses atherosclerotic disease in vascular wall
What is the gold standard in diagnosing coronary artery disease?
Coronary angiography
What are the goals of treatment for patients with coronary artery disease?
Improve quality of life (reduce anginal symptoms)
Improve quantity of life (reduce risk of fatal events)
How do you approach the treatment of stable coronary artery disease?
Drugs are the backbone and foundation of treatment in all patients
Revascularization in select patients - stents or bypass grafting
How are nitrates effective in treating CAD?
Cause venodilation which reduces LV volume, wall stress, and myocardial oxygen demand
Causes maximal coronary vasodilation
Useful in patients with spasm
need to provide nitrate-free intervals since tolerance can develop
no long-term survival or reduction in MI risk; SYMPTOM RELEIF ONLY
What is an important aspect of the dosing/prescribing of nitrates for chest pain?
To incorporate nitrate-free intervals since tolerance can develop
How are beta blockers effective in treating CAD?
Reduce myocardial oxygen demand by slowing heart rate and decreasing force of contraction via beta 1
Increases duration of systole may also increase oxygen supply
Benefits symptomatic patients, those with prior MIs, and those with heart failure
What are some side effects of beta blockers?
May provoke bronchospasm - use with caution in asthmatics
Heart block or significant bradycardia
Fatigue, sexual dysfunction
may mask reflexive tachycardia from hypoglycemia in insulin-treated diabetics
How does the flow/resistance in the pulmonary circulation compare to that of the systemic circulation?
High flow, low resistance
Due to high capacitance that can acoomodate increases in cariac output
Pulmonary arterioles offer very little resistance (systemic arterioles offer 75% of total resistance)
How does the pulmonary vascular resistance compare to systemic?
1/15th the resistance, due to the large cross sectional area.
(high flow)
What are some causes of pulmonary hypertension?
Left heart disease
Chronic thrombotic and/or embolic diseases
Parenchymal lung disease and/or chronic hypoxemia
Otehrs
What defines pulmonary hypertension?
Resting pulmonary artery pressures:
Systolic > 35
Diastolic > 15
Mean >25
And left atrial pressure < 15 mmHg (not transmitted from left heart back)
Pulmonary arteriolar resistance > 3 wood units
What is the threshold of resting mean pulmonary arterial pressure for pulmonary hypertenison?
> 25 mmHg
Also must check that left atrial (LVEDP) pressure < 15 mmHg to ensure it is not being transmitted back
What are three hallmark features of pulmonary arterial hypertension (PAH)?
Vasoconstriction
Smooth muscle and endothelial proliferation
Thrombosis (in situ)
What changes happen to the pulmonary vasculature in the presence of pulmonary artery hypertensoin?
High flow, low resistance changes to low flow, high resistance
Due to proliferation of endothelial cells and vasoconstriction
What are some mechanisms of PAH?
Homeostatic imbalance of vascular effectors (more vasoconstrictors, prothrombotics, and mitogenesis)
Environmental factors
Genetic factors
What role does prostacyclin and thromboxane A2 play in PAH?
Prostacyclin is a vasodilator, inhibits platelet activation, antiproliferative
TXA2 is vasoconstrictor and platelet agonist
Levels of TXA2 >> Prostacyclin in PAH
What is prostacyclin?
Vascular vasodilator, inhibitor of platelet activation, antiproliferative
Seen in low levels in PAH
What role does serotonin play in PAH?
Vasoconstrictor - promotes smooth muscle cell hypertrophy
Seen in higher levels in PAH patients
Platelets have impaired 5HT reuptake in PAH patients
What role does endothelin 1 play in PAH?
Endothelin 1 is a potent vasoconstrictor, stimulates smooth muscle cell proliferation
Plasma endothelin-1 levels are increased in PAH patients
Levels are inveresely proportional to magnitude of pulmonary blood flow
What role does nitric oxide play in PAH?
Vasodilator, inhibitor of platelet activation adn smooth muscle cell proliferation
Endothelial isoform of NO synthase is decreased in patients with PAH
What role does hypoxia play in the development of PAH?
Acutely - not so much
Systemically - induces vasodilation; Pulmonary bed - induces vasoconstriction
Chronically can lead to structural remodeling, smooth muscel cell proliferation, increased deposition of vascular matrix
What are anorexigens?
Similar to methamphetamines
Found to be associated with higher risks for PAH
What role do anorexigens play in PAH?
Found to be associated with higher risks of PAH
What role do CNS stimulants play in PAH?
Cocaine, methamphetamines have been associated with medial hypertrophy of pulmonary arteries
What role does the TGFβ receptor pathway play in PAH?
BMPR2 (bone morphogenic protein receptor type 2) modulates growth of vascular cells by suppressing it.
Mutations have been identified, but there is incomplete penetrance
What role does the serotinergic pathway play in PAH?
Variant genes increase expression of 5HT receptor
Increases serotonin-dependent vascular remodeling
Higher prevalence of varinat genes among pts with PAH than controls
Still lots unknown
What is the basic model of the development of PAH?
Risk factors + Genetic Predisposition leads to endothelial or smooth muscle cell dysfunction, leading to inflammation, thrombosis, remodeling and progression to disease
Describe the hemodynamic progression seen in PAH.
\
CO - cardiac output
PAP - pulmonary arterial pressure
PVR - pulmonary vascular resistance
RAP - right atrial pressure
What symptoms do we see in PAH patients?
Initially dyspnea, fatigue, maybe chest pain
Later - dyspnea, fatigue, chest pain, syncope, edema
What symptom almost always predates a diagnosis of PAH?
Dyspnea
What physical findings are present in PAH?
Elevated JVD
Tricuspid regurgitation
Pulmonary insufficiency (graham-steel murmur)
Accentuated S2
S3 gallup
Peripheral edema
Hepatomegaly, pulsatile liver, ascites
What EKG findings can you see in PAH?
Only seen in fairly advanced cases
RV hypertrophy
Right axis deviation
Right atrial enlargement
What evidence of PAH can you find on CXR?
Enlargement of central pulmonary arteries
Reduced caliber of peripheral vessels (pruning)
Cardiomegaly with RV enlargement
What is the most effective diagnostic workup tool for PAH screening?
Echocardiogram
Can screen for elevation in pulmonary pressure and rule out left heart disease/congenital heart disease
Must confirm with catheterization
What is the gold standard for diagnosing PAH?
Cardiac catheterization to measure pressures
What general measures must you ensure patients with PAH are taking?
Maintain oxygen saturation (maybe give oxygen, minimize low oxygen environments)
Routine vaccination - flu, pneumovax
Avoid vasoconstrictors (nicotine, sympathomimietics)
Avoid deep valsalva maneuvers
Avoid pregnancy
How can you treat PAH medically?
Diuretics to reduce volume overload
Digitalis may be useful in patients with LV dysfunction
Warfarin to mitigate prothrombotic state associated with PAH
Oxygen, when seen in chronic hypoxemia
How do diuretics help PAH patients?
Treats symptoms of volume overload
How does digitalis help PAH patients?
Unclear, but may be most useful with concomitant LV dysfunction
How can warfarin help PAH patients?
Treat prothombotic state associated with PAH
How can oxygen help PAH pateints?
Combats hypoxemic state that can worsen PAH
How can calcium channel blockers help PAH patients?
Benefit is only seen in a minority of patients
Rationale is to vasodilate patients
How do CCBs, endotheilal receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids help treat PAH?
Inhibit endothelin pathway, nitric oxide pathway, prostacyclin pathway that are all implicated in the development of PAH
What are key pathologic features of PAH?
Vasoconstrition
Cellular proliferation
Thrombosis
What are the targets of existing treatment approaches to PAH?
Reversing the underlying patholoic disturbances common in PAH
