1

HEMODYNAMICS & CARDIAC ADAPTATION1. Myocardium histology review

a. Striated muscle with branching, central nuclei, intercalated disksb. Also collagen, glycogen-rich conducting tissue, caps, coronaries in

epicardial fat, SR/T-tubules impt for Ca release/continuation of APc. H band and I band shorten in contraction, A band does not

2. Normal cardiac cyclea. LV > aortic valve > systemic circ > RA > tricuspid > RV > pulm valve > pulm a > lungs > pulm v > LA > mitral valve > LVb. AV valves have papillary muscles w/chordae tendinae attached, semilunar valves lack bothc. Mitral valve is the only one that has 2 cusps, the rest have 3 (can see congenital bicuspid malformation of aortic valve)

3. Definitionsa. Preload

i. volume (or pressure load) of blood present at start of contraction, basically the EDVii. reflective of venous filling pressure and maximal diastolic LV stressiii. determines myofiber length prior to contraction and therefore potential speed/force of contraction (Starling’s Law)iv. clinical: increases in preload cause eccentric hypertrophy

b. Afterloadi. pressure the contracting LV has to push against during systole, basically the SBP or PVRii. clinical: increases in afterload cause concentric hypertrophy

c. Contractility i. intrinsic capacity of myocardium to contract, independent of preload/afterload, due to increased velocity of

shorteningii. clinical: increased by exercise, catecholamines, inotropes; decreased by ischemia (lack of ATP), acidosis

d. Compliancei. distensibility, directly impacts preload (i.e. more distensible = easier to fill = higher EDV)ii. clinical: ↓ compliance from hypertrophy (HTN), fibrosis (pericarditis), ischemia (MI), edema (pulm congestion)

e. Frank-Starling (SV or CO on y-axis vs. EDV or preload on x-axis)i. normal: increase in preload increase sarcomere stretch increase energy of contraction increase COii. heart failure: lower contractility/flatter slope, need to find balance b/w increasing preload (which would increase

CO and thus maintain good perfusion) and preventing pulm edemaiii. athlete: higher contractility/steeper slopeiv. if preload is too low hypotension; if preload is too high pulm edema

f. LaPlacei. wall stress = ½ (Pwall

x radiuswall / thicknesswall) (think: balloon pops when filled)ii. clinical: chronic ↑wall stress due to dilatation (↑radius) induces hypertrophy ↑wall thickness to balance wall

stress b/c ↑wall stress limits myocardial perfusion via coronary flow (BUT ↑ wall thickness ↓ compliance)g. Ejection Fraction

i. % of EDV that is actually pumped out each beat, EF = SV / EDV, normal is 55-70%h. Stroke Volume

i. Volume of blood pumped with each systole, SV = EDV – ESV, normal is 70-90 mLii. Regulated by preload (↑SV w/ ↑PL), afterload (↓SV w/ ↑AL), contractility (↑SV w/ ↑contractility)

i. Cardiac Outputi. Volume of blood pumped by heart per minute, CO = SV x HR, normal is 5 L/min

1. HR is ↓ by vagal (PS) tone and ↑ by SS toneii. Measure via:

1. Fick’s Methoda. CO = O2 consumption (estimated @ 125) / AV oxygen difference (O2Pul a – O2Pul vein)

i. Oxygen content = O2 sat·Hgb [ ] ·Vol%·10 (where vol% = 1.36)b. Use for low output states, a-fib

2. Indicator Methoda. CO = rate of temperature inc of cold saline from RA > pulm a, or rate of dilution of dyeb. Use for high output states (hyperthyroidism)

3. Dopplera. Actually gives you SV by measuring outflow at aortic valve (that x HR = CO)b. Use for beat-to-beat and for determining severity of valvular dz

j. Cardiac Indexi. Normalizes CO to a persons size, CI = CO/Body Surface Area

4. PressuresSite SBP (mm Hg) DBP (mm Hg)RA ------- 5RV 25 5

Pulm a 25 10LA ------- 10LV 120 10

a. LA (aka PCWP or pulmonary capillary wedge pressure where balloon floated to block RV outflow tract, effectively determining the pressure on the other side of the pulmonary circulation, the PVP (pulmonary venous pressure) which is equal to LA pressure which in turn determines the magnitude of the EDV in the LV)

b. During diastole, pressures in the atria/ventricles should be equal, since the AV valves are openc. O2 sat should be about 75% in RA/RV/pulm a and 100% in PCWP/pulm v/LA/LV (important when determining shunts)

5. Resistance = mean pressure gradient / mean flow in dynes·sec·cm-5 or Woods unitsa. SVR = (Mean arterial pressure – RA pressure) / CO, normal is 900-1300 and at least 10x the PVR

i. HI = vasoconstricted / LO = vasodilated (ex: hi CO state, anemia, AV fistula)b. PVR = (PA pressure – PCWP) / CO, normal is 40-90

6. Shuntsa. If LR, see increase in O2 in right heart; if RL, see decrease in O2 in left heartb. ASD causes LA RA shuntc. VSD causes LV RV shunt

2

d. Patent ductus arteriosus causes aorta pulm a shunte. Eisenmenger’s Syndrome

i. LR shunt causes pulm congestion/↑PVR which causes right-sided hypertrophy until eventually the pressure is greater in the R heart than the L heart and the direction of the shunt switches to a RL shunt

7. Hypertrophya. An increase in myocyte volume (more sarcomeres/mito) in response to chronic abnormalities of wall stressb. Reactive hypertrophy is non-pathological and usually affects all chambers (myocardial work NOT increased)

i. Athletes, or any appropriate response, i.e. surrounding healthy myoctes near MIc. Concentric – increased thickness:vol ratio

i. Due to increase in afterload, (ex) HTN, aortic stenosisii. Sarcomeres laid in parallel to increase thickness decrease wall stress (good) + decrease compliance (bad)iii. Cardiac work is maintained at elevated level, thus compensatory increase preload to maintain higher CO

d. Eccentric – normal thickness:vol ratioi. Due to increase in preload (ex) aortic/mitral regurgitationii. Sarcomeres laid in series to dilate chamber increase compliance (good) + increase wall stress (bad)iii. Higher wall stress = stimulus for concentric hypertrophy sarcomeres in parallel too dilated chamber with

normal wall thickness (seen as enlarged heart on xray)iv. Cardiac work maintained at elevated level

e. Clinical consequences of hypertrophyi. Increase in collagen decrease in complianceii. Hypertrophy faster than capillary growth perfusion deficit/reduced coronary reserveiii. Decreased myosin ATPase activity impaired contractility

8. Remodeling – refers to LV volume ↑ and shape change in Pts w/ acute MI due to slippage of myocytes in days following MI9. Failure

a. Circulatory failure – insufficient oxygen delivery to tissues (may be independent of heart function)b. Heart failure – insufficient pump function (may be myocardial failure, valve rupture, etc)c. Myocardial failure – insufficient myocardial contractile function

i. Not every Pt in myocardial failure is in heart/circulatory-failure (which always have systemic adaptations) b/c of compensation, usually via increasing preload to maximize CO

1. If h/c-failure results despite adaptive measures like hypertrophy/dilation = decompensationii. Hallmark is low SV despite high preload (flat Frank-Starling curve) so ↓EF + poor response to ↑ afterload

10. Aginga. Normal changes: lipofuscin, protein x-linking w/ glucose, oxidative damage, decrease VO2 max (O2 consumption)/max HR/A-V

02 diff, decrease SV (thus an increase preload to maintain CO), impaired β-adrenergic fxn (higher levels of catechols but less sensitivity to them)

b. CV aging alters the substratei. Arteries become rigid, dilated, filled w/ plaquesii. Elastic collagen is replaced w/ rigid collageniii. High glucose x-links proteins (caramelization) → reduced elasticityiv. Earlier return of reflected pressure wave adds resistance (i.e. increases afterload) to LV → hypertrophy and stiffening

1. As LV contracts, young compliant aorta stretches/stores potential energy and remaining energy generates the pulse wave velocity that pushes blood thru the systemic circulation. In old person where aorta stretches less and less LV contraction energy stored in stretched wall as potential energy, more energy converted to pulse wave velocity so blood moving faster/reflected back faster at aortic valve.

2. More common for reflected wave to reach aortic valve while it’s still open in women b/c aorta shorterc. Age related changes of the LV: hypertrophy/myocyte enlargement, fibrosis, impaired relaxation (can > LA hypertrophy/a-

fib)d. Aging and HTN: increase arterial stiffness > increase BP/aortic impedance > increase afterload > LV hypertrophy > (1)

increase in LV EDP > increase LA size > a-fib, (2) increase in 02 demands > ischemia, (3) impaired diastolic fxn > CHF

CORONARY PHYSIOLOGY1. Blood supply of the heart

a. RCA: supplies inferior/right heart, courses in right AV groove, can give rise to conus arteryb. LCA: branches into…

i. Left anterior descending (LAD) – supplies anterior/apical heart, courses in anterior IV groove1. Gives rise to diagonal branches which supply anterior LV2. Gives rise to anterior septal a which supply anterior 2/3 of IV septum

ii. Left circumflex (LCF) – supplies posterior/lateral heart, courses in left AV groove

3

1. Gives rise to marginal branches which supply lateral LVc. Dominance defined by which artery (RCA or LCF) gives rise to posterior descending artery/supplies the AV node (SA ½:½)

i. PDA supplies posterior 1/3 IV septumii. 90% people are right dominant meaning that RCA gives rise to PDAiii. 10% are left dominant where LCF continues to crux and gives rise to PDA

d. Anterior papillary m = LAD/LCF, posterior papillary m = LCF/RCA (poorer supply than anterior)i. postero-medial papillary m of mitral valve only supplied by PDA so MI involving PDA can cause mitral regurg

e. Venous return from coronary blood flowi. Thebesian veins drain blood feeding RV into RV (small w/ little flow)ii. Anterior cardiac veins drain RV into RA (intermediate size)iii. Coronary sinus drains 85-90% of blood feeding LV to RA; in left AV groove

2. Myocardial O2 consumptiona. Coronary blood flow (O2 supply) is directly proportional to myocardial oxygen consumption (O2 demand)

i. Supply/demand must be linked since anaerobic metabolism is insufficient and extraction is near-maximalb. Increased heart rate, preload/afterload (wall stress), contractility will increase demandc. Increased coronary perfusion pressure/decreased resistance will increase supply (remember: Q = P/R)

3. Factors which regulate coronary blood flow:a. Anatomic:

i. Perfusion pressure drop when epicardial coronaries branch/pierce myocardium to feed subendocardium ↓ in flowii. Collateral vessels can provide additional routes for flow in atherosclerosis if occlusion is gradual

b. Hydraulic: most coronary flow occurs during diastole when heart is relaxed and not squeezing vessels shuti. Sub-endocardium contracts more than epicardium greater restriction of blood flow during systoleii. To make up for that + increased wall stress due to EDV + ↑ O2 demand VD of sub-endo vesselsiii. VD in sub-endo allows for homogenous blood flow but decreases VD reserve = ↑ risk of ischemia

c. Autoregulation: can refer to maintenance of flow/perfusion across myocardium despite changes in resistance throughout thickness or to maintenance of flow over wide range of perfusion pressures

i. Vessels decrease resistance via VD using “vasodilatory reserve”ii. In fixed stenotic lesion (pressure<60), vessels already maximally dilated and autoregulation not possible ischemia

d. Metabolic: adenosine is the most important mediator of VD in autoregulation (also acidosis, CO2, prostaglandins)i. Metabolic vasodilation is predominant mechanism controlling coronary blood flow in normal heart and is driven by

O2 consumption demands of myocardiumii. However, when atherosclerosis results in obstruction of coronary flow, hydraulic/anatomic/neural/humoral factors

assume much greater importancee. Neural: net effect sympathetic tone is VD (β2 outweighs )

i. β2 cause vasodilation (isoproterenol) while1/2 cause vasoconstriction (clonidine, methoxamine)f. Humoral: intact endothelium helps regulate vascular tone and coagulant state

i. NO will VD normal vascular SM via guanylate cyclase activation, nitroglycerine will work even if endothelial cells damaged b/c is metabolized to NO in SM cells

1. NO and platelet-derived prostacyclins inhibit platelets and VD2. Both HTN and atherosclerosis impair NO release by endothelium

ii. Endothelin-1 causes VC and is stimulated by thrombin/angiotensin II/epiiii. ACh will VD normal endothelium by ↑NO but VC if it’s damaged (i.e. in HTN/atherosclerosis) by causing

direct VC or vascular SM4. Ischemia = inadequate perfusion/flow occlusion low tissue O2 (hypoxia) and inadequate waste removal angina

i. Atherosclerosis pressure gradient across the lesion (lower P distally) decreased flow compensatory VD of distal vessels increases flow at the expense of VD reserves

ii. Eventually vessels are max VD, so in periods of high O2 demand, perfusion pressure is insufficient ischemiaiii. Fixed stenotic lesion >70% = ischemia w/ exercise, if >90% = ischemia at rest

b. Metabolic consequences: decreased HEP (high energy phosphate → ATP and creatine PO4 stores), activation of anaerobic glycolysis w/ production of lactate (heart usually takes up lactate but here it produces it)

c. Fxn’al consequences: i. ↓systolic contraction w/in seconds of ischemia onset (get hypokinesis (uniform shortening↓)/akinesis (no

shortening)/dyskinesis (paradoxical lengthening) effects on myocardial fiber shortening w/ ↑ing decrement in blood flow) and ↓ diastolic relaxation (get ↓ compliance) result in lower coronary perfusion gradient

ii. Myocardial stunning: reversible loss of fxn/contractility due to acute ischemia → fxn returns days post-reperfusion1. Often seen after thrombolytics given for an MI (flow re-established by function lags behind)

iii. Myocardial hibernation: reversible loss of fxn due to chronic ischemia where fxn returns immediately post-reperfusion

iv. <15-20 min of ischemia is normally reversible (attack of angina)

EKGs1. Four phases of cardiac AP

a. Phase 0 – Na+ channels open (massive Na influx depolarization)b. Phase 1 – Na+ channels close, K+ channels open (K efflux slight repolarization)c. Phase 2 – Ca+ channels open, K+ channels stay open (Ca influx balances K efflux plateau)d. Phase 3 – Ca+ channels close, K+ channels stay open (hyperpolarization)e. Phase 4 – ATP-Na/K Pump re-establishes resting membrane potential

i. Fast response = atrial/ventricular myoctyes (0.3-1 m/s) and Purkinje fibers (1-4 m/s)ii. Slow response = SA/AV node (0.02-0.1 m/s)

1. SA node is intrinsic pacemaker (60-100) due to overdrive suppression of slower automaticity foci a. In upper posterior wall of RA

2. AV node is sole structure capable to conduct depolarization to ventriclesf. Depolarization is a wave of positive charges contractiong. Repolarization is a wave of negative charges relaxation (at rest, negative intracellular charge)

4

2. Logisticsa. Paper

i. Horizontal is time, small sq = 0.04s, large sq = 0.2s, 5 large sq = 1sii. Vertical is deflection, small sq = 1mm (amplitude) = 0.1mV (voltage)

b. Limb Leadsi. Measures the frontal planeii. LI/aVL – lateral leads, LII/LIII/aVF – inferior leadsiii. Bipolar leads (Einthoven’s Triangle) -+-++- clockwise from top L

1. LI: R arm negative, L arm positive (+0°) 2. LII: L foot positive, R arm negative (+60°) 3. LIII: L foot positive, L arm negative (+120°)

iv. Unipolar Leads1. AVL – L arm positive (-30°)2. AVF – L foot positive (+90°)3. AVR – R arm positive (-150°)

c. Chest Leads i. Measures the transverse plane w/ unipolar leadsii. V1/V2 – R leads, V3/V4 – septal leads, V5/V6 – L leadsiii. Placement:

1. V1 – 4th intercostals space (ICS), R of sternum2. V2 – 4th ICS, L of sternum3. V4 – 5th ICS, midclavicular line4. V6 – 6th ICS, midaxillary line5. V3 is placed b/w V2 and V46. V5 is placed b/w V4 and V6

d. Vectorsi. (+) charges toward or (-) charges away from (+) electrode = (+) deflectionii. (+) charges away from or (-) charges toward (+) electrode = (-) deflectioniii. (+) OR (-) charges perpendicular to (+) electrode = biphasic (+/-) deflectioniv. Recall that (+) charges represent depolarization wave while (-) charges represent repolarization wave

3. Atrial Depolarization = P wave (<0.8s)i. Reflects SA AV node, vector = leftward, downward, forwardii. Look for +P in LII (max amplitude normally) and biphasic in V1 (and LIII)

b. PR interval = time b/w atrial contraction and ventricular contraction (normally <0.2s or 1 large sq)i. Since AV node is slow response, conduction is slowed delay (shown as PR segment) allows for ventricular filling

4. Ventricular Depolarization = QRS complex (<0.1s)i. First (-) deflection always = Q wave, first (+) deflection always = R wave

1. QS wave occurs when there is no R wave so can’t determine Q or S (count as Q if looking for Q waves)ii. Q wave – septal depolarization, vector rightward (b/c L bundle faster), downward, forward

1. Traditionally represented as negative, thus, look for Q in LI, aVL, V5-V6iii. R wave – “early” ventricular depol toward ventricular apex, vector leftward, downward, forward

1. Positive deflection in LI and LII (negative deflection in AVR) and + deflection w/ ↑magnitude from V1-6iv. S wave – “late” ventricular depol toward ventricular bases, vector leftward/upward (since L heart bigger)

1. Traditionally represented as negative, especially in avF, but + in LI and AVLb. R wave progression – becomes more positive from V1V6 (vs S wave becoming less negative from V1V6)c. Transition Zone – when + deflection of R wave is equal to – deflection of S wave

i. Normal = transition zone in V3 or V4ii. Right axis rotation = transition zone in V1 or V2iii. Left axis rotation = transition zone in V5 or V6

d. ST segment: represents plateau phase of fast response fiber AP, elevated in STEMI/depressed in NSTEMI, angina5. Ventricular Repolarization = T wave

a. Vector rightward/upward (but (-) charges)i. Opposite direction and opposite sign of R wave, thus P and T waves look similarii. General rule is that if the QRS is +, the T wave should be + as well

b. QT interval (beginning Q ‘til end of T)i. Represents whole of systole, clinically used as indicator of repolarization

1. Prolonged QT interval = risk for arrhythmiasii. Normal QT interval < ½ the R-R interval (if the HR is w/in normal limits)

6. Heart rate a. = # of QRS complexes per minute

i. Look for R wave peaking on line of big square ii. Rate is approximated # of big squares to next R (300, 150, 100, 75, 60, 50)iii. In cases of slow or irregular heart rates, count how many QRS complexes w/in 6 seconds (30 large sq), then x10

b. Overdrive suppression is mechanism by which faster beating pacemakers take priority to alternative automaticity focii. SA node pacemaker gives a “sinus rhythm” of 60-100bpm

1. Sinus tachy/brady is when rate is fast/slow but the heart is still under control of the SA nodeii. Atrial automaticity foci rate = 60-80bpmiii. Junctional automaticity foci rate = 40-60bpm iv. Ventricular automaticity foci = 20-40bpm

7. Mean QRS axis a. Determination

i. Look at QRS complexes in LI and AVF

Designation Axis LI AVFNormal 0° to +90° + +

5

Left axis deviation 0° to -90° + -Right axis deviation +90° to 180° - +

Extreme RAD or Undetermined axis -90° to 180° - -

ii. Look for most biphasic QRS complex of limb leads and move from that lead’s postion 90° in the direction of the quadrant identified above to determine more exact mean QRS axis

b. Clinical relevancei. Tall/thin individuals – vertical heart (not pathological), apex points at 90°ii. Obese individuals – horizontal heart (not pathological), apex points at 0°

1. So, if see biphasic QRS complex in LI or AVF, consider it as + so as not to assume an axis deviation when in fact you simply have one of the above 2 normal variants (must really be – to say it’s -)

iii. Hypertrophy – enlarged heart dominates = deviation of axis toward hypertrophied chamberiv. Myocardial infarction – infracted area loses electrical activity = deviation of axis away from infarct

8. Hypertrophya. Atrial = split P wave in LII, uneven biphasic P wave in V1 (<2.5mm)

i. In atrial dilation, larger chamber will become predominant over the other atrium, thus a splitting of the P wave1. Amplitude of one of the phases is predominant (first – R ; second – L) in V1

ii. Normally atria contract together and P wave is a continuous hump1. If one is hypertrophied, P hump will have an added bump (first – R ; second – L) in LII

b. RV hypertrophyi. Huge R wave in V1 (tends to be bigger than S wave)ii. Right axis rotation (DIFFERENT than deviation) – R wave transition zone moves to V1/V2

c. LV hypertrophyi. Precordial leads – see deep S in V1 and tall R in V5

1. Dx of LVH by Sokolow index = height of V5 R wave + depth of V1 S wave >35mmii. Limb leads – see deep S in LIII and tall R in LI

1. Dx by LVH by Lewis index = height of LI R wave + depth of LIII S wave >25mmiii. Ventricular strain, often associated with LVH, characterized by ST depression/ inverted T wave in V5/V6

9. Infarctiona. Three Stages to STEMI (ST segment Elevation acute MI)

i. 1st stage – T wave peak/T wave inversion (first 10 min of MI)ii. 2nd stage – ST segment elevation (first 15 min of MI) – most commonly seen in ER deptsiii. 3rd stage – appearance of Q waves, which never disappear, thus a sign of previous infarction

1. Q waves are longer (˃0.04s) and at least 1/3 amplitude of R wave of same complexb. Localization

i. Anterior infarction – V1-V4ii. Lateral infarction – LI, AVLiii. Inferior infarction – LII, LIII, AVFiv. Posterior infarction – No leads, thus invert and look at mirror image, then should see ST elevation in V1, V2

c. Pericarditis differs in that there are NO Q waves and diffuse ST elevation (multiple leads)10. Ischemia resulting in angina

a. ST segment depression often associated with T wave inversion

ARRYTHMIAS1. Arise from impaired initiation (SA node dysfxn), anomalous initiation (ectopic foci), impaired propagation (AV/His dysfxn)2. 3 main mechanisms:

a. Enhanced automaticity: β1 stimulation, hypokalemia, hypoxemia, ↑ stretch due to ↑preload or mitral valve prolapsed make slope of slow diastolic depolarization steeper such that HR increases

b. Triggered automaticity: abnormal depol interrupts normal cardiac AP (EADs and DADs)i. DADs due to intracellular Ca overload and ↑HRii. EADs due to marked prolongation of AP

c. Reentry (most common): can be anatomical (due to accessory pathway connecting atria and ventricles as in Wolff-Parkinson-White or WPW) or fxn’al (due to slow conduction region such as infarct)

3. Sinus “arrhythmia” is slight variation in R-R interval due to inspiration, otherwise…4. ALWAYS ALWAYS ALWAYS have a continuously varying R-R interval, this is the definition of an arrhythmia

a. Ablation is curative for many types of arrhythmias (surgical removal of tissue causing the problem)5. Irregular rhythms (atrial ectopic foci)

a. Wandering pacemaker: pacemaker activity wanders from SA node to atrial foci i. P’ waves (not from SA node) of different shapes, rate <100, irregular ventricular rhythm (continuously varying R-R)

b. Multifocal Atrial Tachycardia: same as WPi. Same as WP but rate >100, assoc w/ COPD due to chronic hypoxia

c. Atrial Fibrillation: multiple atrial foci with very rapid ratei. No complete atrial depol b/c of rapid rate, thus no P waves, only a segmented baseline

6

ii. AV node acts as a filter to allow only a few impulses to depol ventricles = protective (still irregular R-R)6. Escape (SA node failure)

a. Escape rhythm is when SA node fails completely alternative automaticity focus escapes and paces at its inherent rateb. Escape beat is when SA node fails transiently alternative focus produces single escape beat before restart of sinus rhythm

i. Atrial escape: pause + P’ waves with varying morphology + normal QRS; inherent rate 60-80 ii. Jxn escape: pause + no P wave + normal QRS; inherent rate 40-60

1. Jxn beat MAY produce retrograde atrial depol, seen as inverted P’ waveiii. Ventricular escape: pause + no P wave + huge wide QRS; inherent rate 20-40

1. Due to complete failure of SA node + atrial/jxn foci OR 3rd degree AV block2. QRS becomes wide when ventricle depolarization via regular myocytes rather than Purkinje fibers3. May cause cerebral hypoperfusion (Morgagni-Adams-Stokes) and episodes of syncope

7. Premature beats (irritable foci) – atrial, junctional, and ventricular typesa. A beat is generated earlier than expected in the normal rhythm due to an irritable focusb. PAB (premature atrial beats): P’ wave (or too-tall T wave) + normal QRS + pause

i. SA node is depolarized by PAB and resets in step w/ it, thus a refractory pause before the next cycleii. PAB w/ aberrant ventricular conduction: usually ventricles are able to be depol by PAB, but if one of the bundle

branches has not completely repol, there will be non-simultaneous depol of ventricles slightly widened QRSc. PJB: no P wave (or inverted P’ wave if it produced retrograde atrial depol) + normal QRS + paused. PVC: no P wave (hidden w/in QRS) + huge QRS + pause, DUE TO ISCHEMIA

i. SA node discharges on schedule, so P-P intervals are regularii. Pause has nothing to do w/ resetting of SA node, it’s b/c ventricles are not repol yet when normal stimulus arrivesiii. Unifocal or multifocal (many foci producing different QRS morphologies)iv. 3+ PVC in a row is called ventricular tachycardia, >30s is called sustained VT

1. PVCs caused by ischemia/hypokalemia/anti-arrhythmic drugs/mitral valve prolapse (MVP)v. R on T = when PVC falls on middle of T wave, this is really bad b/c ventricle is vulnerable here to developing VTvi. MVP produces benign PVCs (papillary m stretched during systole local ischemia activation of irritable foci)

1. More common in womene. Any of the premature beats can occur in bigeminy/trigeminy/quadrigeminy (repetitive pattern w/ premature beats dispersed

after given # of regular sinus beats)8. Tachyarrhythmias (sudden series of very fast beats)

a. Paroxysmal Tachycardia = rate 150-250i. Paroxysmal Atrial Tachycardia: P’ wave followed by QRS-Tii. PAT w/ AV Block: two P’ waves followed by QRS-T, think digitalis toxicity esp. if hypokalemiciii. Paroxysmal Jxn Tachy: no P wave (or inverted P’ if retrograde atrial depol) followed by QRS-T, may involve reentryiv. PAT/PJT (aka supraventricular tachy or SVT) w/ aberrant ventricular conduction: above + wide QRS (<0.14s)v. WWP: bundle of Kent is accessory pathway which connects atria/ventricles shortened PR interval aka delta wavevi. LGL (Lown-Ganong-Levine): James bundle is the accessory pathway no PR interval w/ P-QRS-T right in a rowvii. Paroxysmal Ventricular Tachy or simply VT: no P wave (hidden) + huge QRS (>0.14s), basically a run of PVCs

1. SA node continues to pace normally and occasionally, an atrial depol ventricular depol, seen as normal QRS within all the crazy PVCs (capture beat) or normal QRS fused w/ PVC (fusion beat)

b. Flutter (single foci) = rate of 250-350i. Atrial flutter: still get complete atrial depol→ seen as series of P’ waves (sawtooth), every 3rd one depol ventii. Ventricular flutter: still get complete vent depol→ seen as series of smooth sine waves

1. Despite depol, the rate is too high to eject blood decreased coronary perfusion ischemia multiple irritable foci ventricular fibrillation (type of cardiac arrest requiring CPR and defibrillation)

c. Fibrillation (multiple foci) = rate of 350-450i. Atrial fibrillation: no identifiable P waves, jagged baseline w/ a few QRS ii. Ventricular fibrillation: totally erratic

9. Blocks a. Sinus block: temporarily fails to fire dropped beat w/ pause (maybe escape beat)

i. Sick Sinus Syndrome (SSS): SA node dysfxn + failure of all supraventricular automaticity foci marked sinus bradycardia (sometimes w/ intermittent episodes of SVT)

b. AV Block: slow/eliminate conduction from atria to ventriclesi. 1st degree block: prolonged PR interval >0.2s, usually benignii. 2nd degree block:

1. Wenckebach (AV node affected): progressively lengthening PR interval until P wave is not followed by a QRS complex, then restarts (QRS complexes normal)

2. Mobitz (Purkinje fibers affected): some P waves just don’t make it to ventricles (normal PR w/ wide QRS)a. conduction ratio - # of P attempts:# of conducted beats; ex: 3:1 means 2 blocked/ 1 conductedb. pathological , must Tx w/ pacemaker (vs. Wenkebach, which is benign)

iii. 3rd degree block: complete block of SA impulse (P waves still regular!), QRS escape rhythm is jxn’al or ventriculariv. Bundle Branch Blocks: block localized in either R or L bundle branch ventricles depolarize asynchronously

1. Two QRS complexes are recorded a wide QRS complex with R-R’ spike2. RBBB complexes (NOT pathological) seen in V1/V2

a. Brugada Syndrome – familial condition caused by dysfunctional Na channelsi. RBBB assoc w/ ST elevation in V1-V3 w/o coronary occlusionii. Causes ~50% sudden death in healthy people w/o structural heart dziii. Need implant device to detect VT/VF and deliver shock

3. LBBB complexes are seen in V5/V6 and indicate cardiac ischemia11. Steps to EKG Interpretation

a. Rhythmi. P waves present? Look at LII (max +) and V1 (biphasic)ii. Is QRS wide or narrow/normal?iii. Is the rhythm regular or irregulariv. Is the relationship of P to QRS regular?

b. Ratec. Mean QRS Axis

i. Look at LI and AVF for quadrant

7

ii. Find most biphasic limb lead and move 90° toward quadrant identifiedd. Intervals (PR, QT, QRS)e. AV Blocks (PR elongation or T drop)f. BBBsg. Hypertrophyh. Ischemia

HEART SOUND/MURMURS

Systole = S1-S2 Diastole = S2-S1

NORMAL HEART SOUNDSSound Cause How to hear it Notes

S1 Mitral/tricuspid valve closure Diaphragm, over entire precordium

S2 Aortic/pulmonic valve closure

Diaphragm, over entire precordium

Normal splitting of P2 heard only over pulm valve*

Physiologic splitting: pulmonic closes later due to ↑ RV ejection time b/c of ↑ venous return during inspiration (single during expiration)

Pathologic splitting: wide fixed = ASD, narrow fixed = pulm HTN*, reverse split = left BBB, aortic stenosis (closes so late its after P2)

*with pulm HTN, can hear elsewhereS3 Sudden distention of

ventricles during rapid filling

Use bell, at apex

Early diastole“Ken-tuc-ky”

Considered normal in young, healthy ptAlways abnormal if pt >50, assoc w/ heart failure, mitral regurg, VSD (high flow across open valve)

BBB= bundle branch block

S4 S1 S2 S3 S4 S1

EC MS OS

8

ABNORMAL HEART SOUNDSSound Cause How to hear it Notes

S4 Forceful atrial kick in an effort to overcome a stiff ventricle

Use bell, at apex

Late diastole“Ten-nes-see”

Common, as hear if hypertrophied LVAssoc w/ HTN, aortic stenosis, hypertrophic cardiomyopathy

ClicksEjection Opening of stenotic

or deformed semilunars

Over involved valveDirectly after S1

Assoc w/ bicuspid aortic valve or aortic stenosis

Opening snap

Opening of stenotic mitral valve

Diaphragm, at apexDirectly after S2

Assoc w/ mitral stenosis

Mid-systolic Sudden tensing of deformed mitral valve

At apex@ start of murmur

Assoc w/ mitral valve prolapse

Knocks Sudden tensing of the pericardium during rapid filling

At apexEarly diastole (same as S3)

Assoc w/ constrictive pericarditis or restrictive cardiomyopathy

Bruits Turbulent flow due to stenosis

Heard over affected blood vessels

Assoc w/ vascular stenosis

RubsPericardial Inflamed serosal

surfaces rubbing together

At apex Assoc w/ pericarditisDescribed as “squeaky leather”

Thrills Flow obstruction Vibrations felt during systolic flow; assoc w/ aortic stenosis

MURMURS BY TIMINGSound Causes Notes

Systolic Aortic/pulmonic stenosisMitral/tricuspid regurgitation

Between S1S2

holocystolic Mitral regurgitationVSD

Blowing (w/ mid-systolic click if also MVP)Best heard w/ diaphragm at apex radiating to axilla

early Tricuspid regurgitation Heard best along L sternal bordermid-systolic Aortic stenosis (most common) Harsh crescendo-decresendo w/ ejection click

Best heard w/ diaphragm in 2nd RICS radiating to neck

late Mitral valve prolapse Starts once the valve collapses back aka mid-systolic clickBest heard w/ diaphragm at apex

Diastolic Aortic/pulmonic regurgitationMitral/tricuspid stenosis

Between S2S1

early Aortic regurgitation High-pitched decrescendo (sounds like someone breathing out hard)

Best heard w/ bell in 2nd RICS as pt leans forward holding exhalation

mid-diastolic Mitral stenosis Rumbling following opening snapBest heard w/ bell at apex w/ pt in left lat decubitus

continuous Aortopulmonary connectionsArterio-venous connections (AV fistula)

From uninterrupted flow of high P/R to low P/R w/o phasic interruption

Extremely loud murmursMURMURS BY CAUSE

1. A primer on Rheumatic Heart Dza. Post-group A β-hemolytic strep sequelab. Due to Abs to bacterial proteins (SLO and strep DNase B) that resemble proteins of the human heartc. Acute rheumatic fever w/ Sx onset several wks after strep throat

i. Pancarditis1. Aschoff bodies (foci of swollen degenerated collagen surrounded by lymphocytes/plasma cells/MØ

and caterpillar cells)2. Fibrinous pericarditis (“bread and butter”)3. MacCallum plaques (subendocardial thickenings) and small vegetations along valve closure lines/cusps

ii. Migratory polyarthritis of large jointsiii. Subcutaneous nodulesiv. Erythema marginatumv. Sydenham chorea

d. Chronic RHD i. See commissural fusion resulting in “fishmouth” or “buttonhole” valvular stenosis, esp. mitral valveii. See shortening of chordae tendinaeiii. See neovascularization and fibrotic valvular deformitiesiv. See hypertrophy and/or dilatation of chambers pushing against stenotic valves

2. Aortic Stenosisa. Etiology : bicuspid valve (congenital) > rheumatic (usually w/ MS) > degenerative (>65y)b. Pathology : bicuspid = that + heavy Ca, rheumatic = commissural/chordal fusion, degenerative = nodular stenosisc. Hemodynamic : pressure overload (as LV tries to push blood through narrowed valve) increased LV wall stress

compensatory concentric LV hypertrophy decreased LV wall stress at expense of decreased LV compliance LA hypertrophy extra kick to (1) help get blood into a stiff ventricle & (2) increase preload so that CO maintained

d. Heart sound : ejection click (if aortic cusps mobile) followed by harsh crescendo-decrescendo systolic murmur + S4

9

e. Clinical : i. Sx: angina (hypertrophy increased O2 demand but decreased O2 supply due to loss of coronary perfusion

pressure gradient), effort syncope (systemic VD w/ exercise + limited CO hypoTN), long latent periodii. Dx: pulsus parvus et tardus (pulse is slow and bounding due to dampened ejection into aorta) + murmuriii. Tx

1. no Sx = no limitations2. pressure gradient >30 but no Sx = exercise limitations/avoid diuretics3. pressure gradient >50 w/ Sx = surgery (balloon valvuloplasty, only palliative)

3. Mitral Stenosis (MS)a. Etiology : rheumatic heart dz or annular calcification (both more common in women)b. Pathology : commissural fusion, chordal shortening (both are dx of rheumatic), neovascularization of valve (H&E)c. Hemodynamic : pressure/vol overload (LA pushes blood through stenotic valve) (1) LA dilation/hypertrophy a-

fib stasis/thrombosis (2) pulm congestion R heart failure & (3) LV underloading and loss of COi. LV is normal in pure MS

d. Heart sound : opening snap followed by rumbling diastolic murmur + S2 spliti. Longer the murmur, the longer the valve is open, the higher the pressure gradient + more severe the stenosis ii. NO S3 b/c rapid diastolic filling not possible through stenotic valve

f. Clinical: iii. Sx: dyspnea (due to pulm congestion), rales, fatigue (due to decrease in CO), JVD/peripheral edema (due to

right heart failure), infective endocarditis (due to deformed valve, uncommon once valve is really rigid), thromboembolus (due to stasis in dilated LA), hemoptysis, Ortners syndrome (LA becomes very large and compresses the recurrent laryngeal n resulting in hoarseness)

iv. Dx: EKG = p-mitrale (biphasic p waves LII) + inverted p waves V1, CXR = dilated apical pulm vessels, ECHO = “hockeystick” valve leaflets

v. Tx: prophylaxis for rheumatic fever/endocarditis, diuretics (reduce volume overload), digoxin (control a-fib), anti-coagulation (prevent stroke), surgery if indicated (balloon valvuloplasty in pregnant woman w/ MS)

4. Aortic Regurg (AR)a. Etiology : rheumatic heart dz, congenital bicuspid, degenerative Ca, root dilatation (i.e. Marfans), endocarditis, syphilis b. Pathology : rheumatic = retraction, Marfans = abnormal collagen, acute endocarditis = perforationc. Hemodynamic changes :

i. CHRONIC: volume overload (backflow from aorta) compensatory LV dilation increased LV compliance at expense of increased LV wall stress LV hypertrophy (eccentric) + systemic VD increase in SV, coupled with increase in peripheral “run-off” (due to VD) CO maintained (and no ↑ in LV diastolic pressure)

ii. ACUTE: volume overload but LV relatively non-compliant (no time to dilate) flash pulm edema + loss of CO leading to systemic VC/↑afterload which exacerbates AR (also see high LV diastolic pressure b/c dilatation of LV has not occurred to accommodate regurg volume)

d. Heart sound : high-pitched decrescendo diastolic murmur + early systolic murmur (due to increased SV)e. Clinical :

i. Sx: CHRONIC = well tolerated, bounding pulse, lateral PMI / ACUTE = ARD, reflex VC high BPii. Dx: indicative hx + murmuriii. Tx: CHRONIC but Asx = prophylaxis, reduce afterload, CHRONIC w/ sx = valve replacement, ACUTE = surgery

5. Mitral Regurga. Etiology : MVP, rheumatic heart dz, infective endocarditis (acute or chronic), papillary m ruptureb. Pathology : MVP (see below), rheumatic = fibrosis/thickening chordae w/ min Ca/commissural fusion, endocarditis = valve

vegetation, papillary rupture = due to ischemia, thus some possible necrosisc. Hemodynamic changes :

i. CHRONIC = volume overload (backflow from LV) compensatory LA dilatation (a-fib risk) increased LA compliance at expense of increased LA wall stress LA hypertrophy (eccentric) ability to increase preload compensatory LV eccentric hypertrophy increase in SV and CO maintained

ii. ACUTE = volume overload but LA relatively non-compliant (no time to dilate) flash pulm edema + loss of COd. Heart sound : blowing holosystolic murmur (may obscure S1) + S3 w/ parasternal lifte. Clinical :

i. Sx: CHRONIC = well tolerated, some inability to increase SV during exercise / ACUTE = ARD, shockii. Dx: indicative hx + murmuriii. Tx: prophylaxis for endocarditis, diuretics, digitalis, VD (LV flow will take path of least resistance, i.e. ideally out

aorta not back to LA), mitral valve repair w/ LV dysfxn (even if sx mild, want to catch and fix early)6. Mitral Valve Prolapse

a. Etiology : congenital (ie Marfan- AD disorder of fibrillin-1)b. Pathology : myxoid degeneration of spongiosa (see in young women), enlarged mitral annulus, hoodingc. Hemodynamic changes : valve defect valve prolapse into LA during systole, usually associated with some degree of

mitral regurgitation and can cause foci of friction-induced fibrosis/thrombi where leaflets keep slamming into LA walld. Heart sound : mid-systolic click followed by late systolic murmur, louder if squatting (due to decreased venous return)e. Clinical :

i. Sx: usually ASx, murmur is discovered during physicalii. Dx: indicative hx + murmuriii. Tx: prophylaxis for endocarditis, aspirin, rarely surgery

7. Tricuspid Regurga. Etiology : infectious endocarditis (if isolated TR) due to IV drug use, RV enlargement due to left heart failureb. Pathology : endocarditis = vegetation, left failure = enlarged tricuspid annulusc. Hemodynamic changes : left failure pulm congestion/HTN RV dilation/hypertrophy enlarged tricuspid annulusd. Heart sound : holosystolic murmur that increases w/ inspiration (Caravello’s sign)e. Clincal :

i. Sx: hepatomegaly/JVD (due to right failure)ii. Dx: indicative hx + murmuriii. Tx: Tx left failure

8. Pulmonary Regurg (PR)a. Etiology : carcinoid, bacterial endocarditis, rheumatic (only if other valves also affected)b. Pathology : systolic leak from pulmonary art to RV

10

c. Clinical : usually not deleterious on its own b/c R heart can accommodate volume loadsi. Tx: Tx underlying condition

Basic Principles of Stenosis (chronic) → Failure of valve to completely OPEN1. Usually due to chronic scarring/calcification of valvular cusps→ Sx do not develop until the valve area narrows to <1/2 normal2. When area decreases <1/4 of normal area = serious symptomatic stenosis3. With serious stenosis, a pressure gradient exists across the valve orifice with higher pressure than normal proximal to the valve4. proximal chamber hypertrophy and subsequent dysfunction5. Most occurs progressively w/ long latent period Basic principles of Regurgitation (acute or chronic) → Failure of the valve to completely CLOSE1. Regurg causes a volume overload of the chambers proximal and distal to the leaking valve2. The ventricles must pump the normal amount of blood plus the regurgitant blood = increased preload3. Response to increase in preload is eccentric hypertrophy – both dilation and hypertrophy4. Inititally, eccentric hypertrophy increased performance but with significant increases in preload, irreversible damage and sx occur5. Replacement of a regurgitant valve must be done before irreversible damage occurs

VASCULAR DISEASE1. Arteriosclerosis has 3 varieties

a. Athero- and arteriolo- sclerosis (2 of 3) discussed separatelyb. Calcific Medial Sclerosis (Monckeberg Dz)

i. Deposits of Ca w/in media of small/medium muscular arteriesii. Usually incidental and w/o Sx

2. Arteritis or Vasculitis = inflammation of arteries due to direct infxn, immune response, or unknown causes, and are systemica. Auto-immune responses due to ANCAs (anti-neutrophil cytoplasmic Abs) w/ immune complex deposition

i. P-ANCA = perinuclear ANCA = Ab against MPO (microscopic polyangitis)ii. C-ANCA = cytoplasmic ANCA = Ab against proteinase-3 (Wegeners)

b. May also see auto-immune rxn to endothelial cells (Kawasaki)c. Affecting elastic main arteries

i. Temporal Arteritis – segmental vasculitis of temporal/ophthalmic/carotid a. branches, F>50 w/ acute loss of vision; biopsy shows giant cells/granulomatous inflamm disrupts int elastic lamina →fibrosis/luminal narrowing

1. steroid responsive ii. Takayasu Arteritis (“pulseless dz”)– vasculitis of aortic arch and its major branches, F<40 w/ cold fingers, weak

upper extremity pulses, visual deficits, aortic regurg, etc; biopsy shows giant cells/ granulomatous inflamm throughout thickness of vessel wall/aortic root dilation/narrowing of ostia/luminal narrowing

1. NOT steroid responsive unlike the other 2 granulomatous vasculitidesd. Affecting medium/small arteries

i. Wegeners Granulomatosis – necrotizing granulomas in vessels of resp tract/kidneys, 40-50y M w/ (+) C-ANCA, 1. steroid responsive

ii. Polyarteritis Nodosa – affects kidney/GI/heart (NOT lung), transmural focal/episodic vasculitis infarction/ thrombosis, biopsy shows fibrinoid necrosis (immune complexes deposited in artery so complement comes and destroys the vessel wall making it leaky to fibrinogen); young adult w/ episodic fever/malaise/myalgia

1. steroid responsive iii. Thromboangiitis Obliterans (Buerger dz) – recurrent vasculitis in radial/tibial art lead to obliterative thrombi and

inflammation affecting adjacent veins and nerves, 25y M smoker w/ severe pain at rest & gangrenee. Affecting arterioles/capillaries/venules

i. Microscopic Polyangiitis – rxn to Ag (drugs, microbe) see leukocytoclasia (fragmented PMNs), vascular lesions of same age, present w/ hemoptysis/hematuria/palpable purpura & (+) P-ANCA, responsive to removal of Ag

f. Affecting coronaries

11

i. Kawasakis Disease – young child w/ acute febrile illness cardiac complications due to anti-endothelial cell Abs, present w/ 5 classic sx: fever, non-purulent conjunctivitis, palm/sole erythema, desquamation, peripheral edema

g. Affecting Veinsi. Varicose veins due to chronically high pressure and poor wall support (usually NO thromboembolism)

1. Commonly superficial veins of lower extremeties (cosmetic other than poor drainage of area)2. Submucosal varicose veins can bleed fatally

ii. Thrombophlebitis and Phlebothrombosis of deep veins of legs due to stasis and hypercoagulability1. Can lead to pulmonary thromboembolism in addition to leg edema and tenderness

h. Affecting Lymphaticsi. Lymphangitis and Lymphadenitis where bacterial infxn causes vessel/node inflammationii. Lymphedema where obstruction of vessels/nodes leads to proximal dilatation and edema of affected area

3. Aneurysms = abnormal focal dilatation of vessel, usually arterya. True aneurysms are dilatation of intact vessel wall

i. Saccular subtype is focal/spherical/vascular outpouching and is usually more surgically-resectable b/c it involves only part of the vessel wall, not entire circumference

ii. Fusiform subtype is linear dilatation involving entire circumference of vessel (most AAAs)b. False aneurysms are collections of extravascular blood that is contained from rupture only by CTc. Atherosclerotic – most common, fusiform type, M>40 w/ subrenal AAA (abd aortic aneur), rupture = death, Tx by graftd. Syphilitic – fusiform type, ischemic destruction of elastic tissue of thoracic aorta (aka tree barking) due to obliterative

endarteritis of the vasa vasorum vessels (by lymphocytes and plasma cells) that feed large arteriesi. Unlike atherosclerosis, usually affects aorta at its root (dilatation of aortic arch) aortic regurgii. See ribbon-like effect on aortic intima w/ alternating bulges into lumen that can cause turbulence/↑thrombus riskiii. Complications include aortic insufficiency due to dilatation of aortic valve ring, superimposed atherosclerosis leading

to narrowing of coronary art ostium/ischemic heart dz, and compression/erosion of adjacent structurese. Dissection– transverse intimal tear in proximal aorta (usually near aortic valve) dissection of blood down laminar plane b/w

inner 2/3 and outer 1/3 of aortic wall death w/o surgeryi. Either 50yo M w/ HTN (not assoc w/ atherosclerosis) or Pt w/ CT abnormality (Marfans/Ehlers Danlos) w/ acute onset

excruciating chest painii. Cystic medial degeneration more common if CT abnormality (replacement of elastic tissue w/ ECM)iii. Classification

1. Type A (proximal) are most common and involve ascending aorta +/- descending aorta2. Type B (distal) only involve descending aorta beyond branching of L subclavian art

4. Vascular Tumorsa. Benign

i. Vascular ectasias (dilatations) present in skin/mucosa1. Congenital = nevus flammeus

a. Flat reddish-purple rgns on head/neck that usually regressb. Larger port wine stains, which often enlarge rather than regress

2. Acquired = spider telangiectasia assoc w/ ↑ E23.

ii. Hemangioma = blood filled cap1. Capillary subtype are red/blue spongy lesions that often spontaneously regress2. Cavernous subtype are reddish-blue spongy honeycomb mass

a. Dilated caps filled w/ blood or thrombi but endothelium normalb. Generally do NOT regress

iii. Lymphangiomas (capillary and cavernous subtypes)1. Capillary looks like blisters2. Cavernous usually in neck (cystic hygroma) and will require surgery

b. Malignanti. Kaposi’s sarcoma – classic/endemic/epidemic (in immunosuppressed) forms, see nodular reddish-purple lesions

1. Classic (chronic) is indolent dz affecting distal extremeties of old Mediterranean men2. Endemic is aggressive and involves lymph nodes (Africa)3. Immunosuppression-related (HIV) affects multiple organs

ii. Angiosarcoma – affects skin/soft tissue/liver (assoc w/ PVC/Thorotrast/arsenic exposure)/and breast1. Assoc w/ chronic lymphedema and radiation2. Poorly-circumscribed soft invasive mass3. Very POOR Px

12

CORONARY ARTERY DISEASE (ATHEROSCLEROSIS and SYSTEMIC HTN)1. Disease of epicardial vessels, characterized by endothelial dysfxn, vascular inflamm, and intimal buildup of

lipids/chol/Ca/debris plaque formation, luminal obstruction, abnormal blood flow, and target organ ischemia2. Atherosclerosis is leading cause of death in Western countries and can result in embolization/vascular occlusion/aneurismal dilatation

a. Risk Factorsi. Non-modifiable: age, gender, family hx/genetics are most powerful predictors ii. Modifiable: high LDL, low HDL, HTN, DM, smoking, obesity, sedentary lifestyle, type A personality, high

CRP/homocysteine/plasminogen activator inhibitor 1 (all have independent effects on risk, not synergistic)b. Pathophysiology

i. Chronic arterial endothelial injury w/ ↑vascular permeability/endothelium activation/adhesion platelets, monocytes, Th cells fatty streak more lipid accumulation (extracellular cholesterol clefts and foam cells) + SM prolif/migration from media to intima/matrix deposition fibrous cap overlying core of foam cells/chol luminal narrowing due to atheroma

1. Endothelial injury due to oxLDL (inactivation of NO/impaired VD), which is taken up by MΦ/SM cells → foam cells

ii. Repeated cycles of acute changes (rupture, erosion, intra-plaque hemorrhage) ↑risk of thrombus w/ partial/full occlusion

iii. Tends to occur in regions of branching/curvature where there is turbulent flow (lower abdominal aorta/coronaries/carotid)

3. Systemic HTN is elevation of arterial BP resulting in adverse health effects (sustained SBP ˃140 and/or DBP ˃90)a. ↑ w/ age and more common in men (if under 50yo) and blacksb. CV mortality risk doubles w/ every 20/10 increase in BPc. Nearly 1/3 USA adults has HTN (most are over 50, in fact over 2/3 of people over 65 have HTN)d. Risk factor for “metabolic syndrome” along w/ abdominal obesity, high TGs, low HDL, and high fasting glucosee. Long-term anti-HTN Tx significantly reduces CV events including stroke/MI/heart failure

i. Goal of Tx is BP ˂ 140/90 (130/80 if co-morbid DM or chronic kidney dz), esp. if over 50

Designation SBP (mm Hg) DBP (mm Hg)Normal (meet both criteria) ˂ 120 ˂ 80Pre-HTN 120-139 80-89Stage I HTN 140-159 90-99Stage II HTN ≥ 160 ≥ 100

f. Identifiable causes include sleep apnea, drugs, chronic kidney dz, primary aldosteronism, thyroid dz, cushing’s, coarc aorta, etc

g. Classification:i. Primary or essential HTN (majority)

1. Genetics/family hx and environmental factors contribute

13

ii. HTN secondary to another condition such as pregnancy/pheochromocytoma/coarctation of aorta/endocrine dysfunction or, most often, renal dz w/ chronic activation of the renin-angiotensin-aldosterone system

1. Atherosclerosis +/- superimposed thrombus at origin of renal artery (common in old men) will cause kidney to perceive hypovolemic state (I’m not getting enough blood!) and to activate renin-angiotensin system

2. Fibromuscular dysplasia can occur anywhere along renal a (common in young women) w/ same result3. Note that the kidney on the affected side suffers diffuse ischemic changes, but it’s the kidney on the

contralateral side, the one that has to compensate, that experiences more severe arteriolosclerosis/HTN effects

h. Complicationsi. Vascular pathology resulting in ischemic organ damage

1. Atherosclerosis of large arteries (already discussed)2. Arteriolosclerosis of arterioles and small muscular arteries

a. Hyaline form is most commoni. Leakage of plasma proteins into vessel wall w/ ↑ deposition of basement membrane

material and luminal narrowing (see diffuse pink thickening of wall)b. Hyperplastic w/ fibrinoid necrosis can be seen w/ severe malignant HTN where DBP ˃130

i. small vessel injury leads to leakage of plasma proteins (including fibrinogen) and thrombosis w/ release of GFs that lead to intimal hyperplasia/luminal narrowing

ii. luminal narrowing, depending on location, can lead to renin-angiotensin activation w/ renal vasoconstriction and HTN exacerbation

iii. See onion-skin lesion (concentric proliferation of intimal myofibroblasts) and ECM accumulation

ii. Cardiac dz (LV hypertrophy/CHF)iii. Cerebral hemorrhage

1. Hyaline/hyperplastic arteriolosclerosis and Charcot-Bouchard microaneurysms of small arteries leads to rupture (most commonly in putamen/thalamus/pons)

iv. Renal dz1. Benign nephrosclerosis (common in normal aging; exacerbated w/ primary HTN or DM)

a. See finely granular cortical surfaceb. Larger arteries (arcuate, intralobular) have fibro-elastic hyperplasiac. Small arteries and arterioles have hyaline arteriolosclerosisd. Does ↓ renal blood flow but usually only small ↓ in GFR

2. Malignant nephrosclerosis (assoc. w/ severe malignant HTN)a. See “flea-bitten” kidney surface w/ petechial hemorrhages on cortical surfaceb. Small arteries and arterioles have hyperplastic arteriolosclerosis w/ fibrinoid necrosisc. May see proteinuria, hematuria, and onset of acute renal failure

4. Chronic Stable Angina (reversible injury)a. Clinical syndrome characterized by chest pain with exertion (pain sensation due to adenosine activating A1 receptors)

i. Class I = no limitation of physical activityii. Class II = slight limitationiii. Class III = moderate limitationiv. Class IV = severe limitation, sometimes w/ Sx at rest

b. Usually due to fixed stenotic lesion (ie atherosclerosis) in an epicardial coronary arteryi. Vessels are maximally VD to increase perfusion (see above), but plaque prevents match of O2 supply/demand

c. Variant (Prinzmetal) Stable Angina (reversible injury)i. Focal vasospasm in addition to stenotic lesion so can see angina at rest in addition to w/ exertion

d. Sx: Retrosternal chest discomfort/heaviness that is relieved by rest/NTGi. Sx vary between pts, but are always the same for an individual pt (if significantly worsen, change, occur

more frequently, or have angina at rest → unstable angina)e. Dx:

i. EKG: ~50% of pts will have a normal resting EKG, otherwise look for ST depression >1mm (or elevation w/ Prinz)ii. Stress test: reproduces the angina Sx via exercise, yet not very specific/sensitiveiii. Imaging: complement stress test and help localize areas of ischemia

1. Coronary angiography is gold standard for identifying vessel narrowing2. Radioisotope uptake (or echo) demonstrates aerobic metabolism

f. Tx:i. Goal is to relieve Sx and, more importantly, prevent progression of CAD

1. Sx relief from sublingual NTG2. Dz modifiers include β-blockers, stents, Tx of modifiable risk factors (ex: statins to lower chol, BP meds)

ii. 2˚ prevention is ASA ASA ASA. All pts should be on aspirin! (unless they have a bleeding disorder/allergy)

14

ACUTE CORONARY SYNDROMES1. Spectrum of diseases which includes unstable angina, MI (NSTEMI, STEMI), and sudden death (LAD most often occluded)

a. Note that most MIs w/ ST elevation (STEMIs) will develop Q waves whereas those w/o ST elevation will be classified as unstable angina or NSTEMI based on whether cardiac enzymes are detectible

b. Rupture of vulnerable atherosclerotic plaque w/ superimposed thrombus is the underlying etiology in nearly all cases c. Exposure of plaque elements coagulation/thrombus formation + VC partial (unstable/NSTEMI) or full (STEMI) occlusiond. Possible to have coronary art vasospasm +/- thrombus and not have atherosclerosise. End result is ischemia switch to inefficient anaerobic metabolism, if >20min cell death

2. Unstable or Crescendo Angina occurs w/ partially occlusive thrombus and results in reversible injury3. MIs

a. Transmural MIs due to completely occlusive thrombus resulting in irreversible injuryi. Can see fibrinous pericarditis 2-3d later due to inflammatory response (“bread and butter”)

b. Subendocardial MIs occur when have a completely occlusive thrombus that is thrombolysed allowing some level of reperfusion, therefore only the highly-susceptible subendocardium infarcts

c. Necrotic area will first be dark red/mottled (12-24h) then pale (1-3d) then soft/yellow w/ hyperemic border (3-10d) and eventually a rubbery white scar (2mo)

i. Affected area is weakest/most susceptible to rupture 4-6d after MI when max breakdown /rebuilding minimal1. LV wall rupture risk greatest in old women2. LV rupture usually leads to hemopericardium and cardiac tamponade but can cause false aneurysms3. IV septum rupture leads to acute L→R shunt4. Papillary m rupture leads to acute MVR

d. Myocytolysis is reversible hydropic change seen in cells adjacent to necrotic areae. Effects of reperfusion

i. Salvage of reversibly-injured cellsii. Myocardial stunningiii. Hemorrhageiv. Contraction Band Necrosis (exposure to Ca causes transverse bands)v. ROS injury

4. Signs/Sx of MIa. Prolonged (>30min) severe crushing chest pain (CP) at rest, radiation to jaw/neck/arms, cool/clammy skin, SOB

i. atypical Sx like fatigue, NVD, MSΔs, esp. in women/elderlyb. NSTEMI tends to have “stuttering” CP as reperfusion through partial occlusion comes and goes

5. Physical Findings (depend heavily on location of ischemia)a. Rales – as EF declines, pulmonary congestion will occurb. S4 – impaired relaxation (ATP-dependent) stiff LVc. Mitral regurg – papillary m becomes ischemic (posterior medial papillary m is perfused only by PDA)d. High JVD – indicative of R infarct, especially if no pulm congestion

6. Lab valuesa. Troponin (TnI/TnT): found only in myocytes so presence indicates cell lysis, virtually Dx of MI (peak at 48h; high for 7-10d)b. CK-MB: creatine kinase specific for myocytes indicates cell lysis (peak at 24h and normal w/in 3d)

7. EKG changes (ST segment elevation, T wave inversion, new Q waves are characteristic)a. STEMI: EKG is abnormal and generally dx of MI

i. ANT infarction (LAD): V1-V4 changesii. INF infarction (RCA): II/III/aVF changesiii. LAT infarction (LCF): V5-V6, I, aVL changes

15

iv. POST infarcts (RCA): consistent chest pain, ST elevation w/ mirrorv. If V1 is involved (1) it’s a proximal occlusion (2) both LV/RV probably involved

b. NSTEMIi. EKG usually normal, dx by elevated serum troponin levels

c. Unstable anginai. EKG is normal, (and since no evidence of troponin/CK-MB), dx is one of exclusion

8. Txa. Acutely: ASA, clopidogrel, heparin, NTG + restart perfusion (90m or less = dramatic benefit)

i. If door to needle <90m, PCI (if stenting, ASA/clopidogrel/IIbIIIa(-) for surgery, continue ASA/clopidgrel post-op)ii. If door to needle >90m, thrombolytics (t-PA)

b. Post-MI: = ASA, clopidogrel, statin, ACE(-), b-blocker (last 3 decrease mortality)9. Vessel involved predicts where the infarct will occur

a. Anterior LV wall – LADb. Lateral LV wall – LCFc. Inferior/posterior – RCAd. Posterior septum – usually RCA (since 90% of people are R heart dominant)e. Extent of collateral blood vessels, duration, and metabolic demand of tissue near the lesion affects extent of infarct

10. Pathological Classificationa. Subendocardial infarction (by definition, does not extend into epicardium)

i. Partially occlusive thrombus from diffuse plaques w/ patchy areas of necrosis, smaller in sizeii. EKG normal

b. Transmural infarction (worse Px)i. Completely occlusive thrombus from single artery w/ solid area of necrosis, large in sizeii. EKG shows Q waves, ST elevationiii. Commonly pericarditis ~3d postMI

1. Dressler’s syndrome = pericarditis due to auto-Ab, 2-10w postMIiv. If posterior infarct, more likely to cause conduction disturbances, as nodes are predominantly supplied by RCA

c. “Wavefront phenomenon” i. Necrosis begins at level of subendocardium (due to less perfusion, higher workload) and expands outward ii. Want to intervene before wavefront expands so that a greater portion of heart can be spared

11. Pathological Findingsa. Contraction band necrosis

i. Hyper-eosinophilic contraction bands indicate reperfusion before death (cells dying in presence of O2)b. Pallor or hyperemia (if reperfusion) w/in 12-24hc. Dating of MIs (after the event)

i. 12 hrs – earliest histologic changes (wavy fiber change)ii. 24 hrs – earliest gross changes (coag necrosis)iii. 1-5 days – neutrophilic infiltrate predominantesiv. 7-10 days – macrophages predominate, beginning granulation tissuev. Weeks – fibrosis

12. Complications of MI a. Pump failure CHF, cardiogenic shock (low CO despite high preload, lethal)

i. ↓myocardial contractility or ↑ resistance to ventricular filling or ejection can cause CHF1. L heart failure

a. Usually see dilatiation of LV then LAb. Assoc w/ dyspnea/orthopnea/Paroxysmal nocturnal dyspnea/cyanosis/↓exercise tolerancec. Here rales on exam due to interstitial pulmonary edemad. See micro-hemorrhages (if chronic will see hemosiderin-laden MØ)

2. R heart failurea. Usually secondary to L heart failure where lung becomes congested and ↑ pressure R side of heart

must pump against or significant lung dz (cor pulmonale)b. Causes backward failure where see systemic congestion/pitting edema

b. Arrhythmiasc. RV infarction (inferior/posterior MI) shows signs of RV failure (ex: high JVP), often assoc w/ LV dysfxnd. Rupture

i. If free wall, 3-5d postMI tamponade, deathii. If IV septum L to R shunt, shockiii. If papillary m regurg, flash pulm edema, shock

e. Ventricular aneurysmi. Very bad b/c get stasis mural thrombus emboli stroke 6 ft underii. Expansion: altered healing which can result in a dilated wall (aneurysm)

1. Caused by dead/healing myocytes being pulled apart from stress of large preload (like eccentric hypertrophy)

2. EKG will show persistent ST elevation in the dilated regioniii. Extension: new necrosis extending from a previous MI

1. Ex: pt develops new onset CP, new ST segment changes, new CK/troponin increases while in postMI periodf. Mural thrombus due to stasis of blood from poor contractile activity or aneurysmg. Pericarditis (see above in “transmural”)

16

BLOOD PRESSURE/HTN1. Epidemiology

a. 65million American, extremely common in population, higher in obese and AA womenb. Hypertension >140/90 or with complications (diabetes/renal insufficiency) >130/80c. CV risk starts below hypertensive stated. People at highest risk have large pulse pressure (high SBP and low DBP), which occurs as arteries lose elasticity

2. Determinants of blood pressurea. Physical – blood volume (balance b/w SV input + output to high capacitance venous system) and arterial compliance (dV/dP)b. Physiologic – cardiac output and peripheral arterial resistance (mainly @ level of arterioles)c. Nuances

i. Ausculatory gap – silent gap between SBP/DBP, true systolic can be missed if pump up cuff to a point in that gapii. Pulsus paradoxus – pathological fall in SBP (>10) during inspiration, common sign in cardiac tamponade

3. Influence of peripheral vasculaturea. If CO and peripheral run-off are equal, BP is constantb. Elasticity of aorta

i. Highly elastic aorta can dampen degree of SBP elevation per stroke volume by storing elastic recoil energy1. Result is continuous perfusion in vasculature and heart can increase CO yet minimize work

ii. Distensibility, i.e. compliance, decreases with age or with diabetes, which widens PP1. Increase in pressure wave reflection increase in systolic + increase in run-off decrease in diastolic

iii. Central Aortic BP is typically lower than brachial a BP and is pressure that brain vasculature is exposed toc. Importance of endothelial integrity

i. NO (from L-arginine via eNOS or endothelial NO synthase) acts correctly on healthy endothelium1. Generates smooth muscle relaxation2. prevents platelet adhesion3. antagonizes angiotensin II–mediated vasoconstriction

ii. “endothelium dysfunction” (often in obesity/diabetes) causes ↑destruction/↓production of NO oxidative stress4. Diurnal variation – BP follows circadian rhythm & is lower at night

a. Non-dippers (night BP doesn’t fall at least 10%) and hyperdippers (falls >20mm) = higher risk for pressure-related CV injury5. Autoregulation – sigmoidal curve, thus perfusion is maintained within a range of blood pressures

a. NOTE: when BP rises, brain & kidney don’t VD to decrease resistance, rather they VC to slow down the flow, this is protective!b. Cerebral Blood Flow

i. As above, important b/c prevents ischemia (if BP falls) and edema (if BP rises)c. Renal Blood Flow – mechanisms act to maintain the GFR

i. Myogenic reflex: increased afferent pressure aff VC lower flow, decreased afferent pressure aff VD more flow

ii. Tubuloglomerular feedback: increased Na at macula densa (i.e. flow is hi) aff VC, decreased Na aff VDiii. Local RAS activation: low Na (i.e. flow is lo) renin release angiotensin II efferent VC more flow

6. Obesity-related HTN is characterized by:a. Increased sympathetic activity – insulin resistant visceral adipocytes release NEFAs into blood, which (1) increase a1

vasomotor tone and (2) decrease NO levelsb. Activation of RAS – angiontensin II Na reabsorption + aldosterone release more Na reabsorption. Thus, less Na is sensed

by JG inappropriate dilation of aff arteriole and eventual destruction of nephrons due to high glomeruler pressuresc. Increase ECF – all the Na reabsorption leads to water retention tood. Hypovitaminosis D/secondary hyperparathyroidism – Vit D3 is sequestered by adipocytes reactive rise in PTHe. Increased Na sensitivity (i.e. requires higher pressure to rid sodium) kidney rises BP to stimulate naturesisf. Pregnancy issues - obese mothers often have low birth wt/premature babies low # glom which lack autoregulatory ability

7. HTN and CARDIO complicationsa. Increased hemodynamic stress plaque ruptureb. Increased stretch of vasculature RAS activation arterial remodeling/hypertrophy vessel narrowing ischemiac. Increased stretch of vasculature also aneurysmsd. Increased afterload LV hypertrophy heart failure

17

8. HTN and RENAL complicationsa. HTN is 2nd leading cause of end stage renal dz or ESRD (DM is 1st) and is also linked to chronic kidney dzb. Nephron loss due to transmission of high SBP into the glomerulus

i. HTN afferent remodels and is fxn’ally incapable of maximally dilating loss of autoregulation1. Autoregulation normally via myogenic reflex (constriction of afferent arteriole when SBP↑ to protect glom)

and tubuloglomerular feedback based on NaCl at macula densa in distal tubule (constrict w/ ↑NaCl)ii. Now, relationship btw SBP/GlomP is close to linear, nephrons cannot tolerate such high pressures and dieiii. As # of nephrons declines, kidney relies on fewer nephrons to maintain GFR at necessary rate & has to compensate

1. Dilate afferent arteriole via prostaglandins and NO2. Constrict efferent arteriole via angiotensin II (RAS = renin-angiotensin system)3. Both lead to higher GlomP which perpetuates cycle

iv. Tx is ACEIs (or ARBs) which will decrease the SBP and thus the GlomP, slowing the damage1. ↓ GFR ↑ sCr, but don’t take pt off ACEI!! Short-term rise in serum Cr due to ↓GFR is lesser of two evils

c. Ischemic kidney due to atherosclerotic blockage of renal artery(ies)i. Unilateral RAS: renal hypoperfusion but NO compromised GFR or expanded intravascular volume

1. Contralateral kidney is fine and maintains GFRii. Bilateral RAS: renal hypoperfusion AND low GFR/expanded intravascular volumeiii. Both cause renal HTN refractory to anti-HTN Tx (bilateral much worse, though diuretics help w/volume overload)

1. ACEIs are contraindicated b/c they exponentially increase sCr irreversible injury

9. HTN and CNS complicationsa. Cerebral blood flow (CBF) is proportional to cerebral oxidative metabolism and is highly pCO2 sensitive (↑ w/ ↑pCO2)

i. Normally autoregulated over wide range of perfusion pressures (sigmoidal curve w/ plateau from 50-150)b. HTN right shift of whole curve, thus upper and lower limits of autoregulation (plateau rgn) are set at a higher overall BP

i. BP below lower limit of autoregulation max VD but still unable to maintain flow ischemia/stroke (can extract more O2 from blood for little while w/ ↓perfusion so some cushion, but can’t maintain very long)

ii. BP above upper limit max VC but still unable to slow flow ↑ hydrostaticP edema/HTN encephalopathyc. BP reflexively rises during acute ischemia (stroke) huge increase in SBP and paradoxical cerebral edema

i. “Watershed” around ischemic area is unresponsive to autoregulation and thus depends entirely on SBP for perfusion (this region is called the ischemic penumbra where cells damaged but still viable)

ii. Instinct is to give anti-HTN meds to prevent edema, but that would worsen ischemia and cause greater infarctiii. DO NOT give anti-HTN drugs unless SBP >230 or DBP ˃130

10. 2° hypertensiona. Hyperaldosteronism – increased aldosterone due to increased renin (usually tumor) increase Na reabsorption high BPb. Pheochromocytoma - neuroendocrine tumor of the adrenal glands or other catecholamine secreting tissues

i. Measure by serum metanephrine levelsc. Pregnancy - normally falls during 1st/2nd trimester but rises back to normal during 3rd trimester

i. Pre-eclampsia – onset of high BP after 20th week of pregnancy, emergency

18

ENDOCARDITIS1. Valve histology:

a. Very few blood vesselsb. Fibrosa = dense collagenous layer facing outflow forcec. Spongiosa = central core of loose CT w/ proteoglycansd. Elastin-rich layer facing chamber receiving inflow (called atrialis or ventricularis)

2. Endocarditis = deposition of adherent thrombotic debris (vegetation) on the valves or mural endocardium3. Infective Endocarditis (most serious type b/c destroy valve leaftlets and can lead to sepsis = medical emergency)

a. Acutei. More virulent orgs (Staph aureus) assoc w/ IV drug useii. Can infect normal valvesiii. Most commonly tricuspid valve (injection via IV use brings orgs to R heart first)iv. Can cause rupture, valve ring abscess, septic infarct, chronic regurg

b. Subacute i. Less virulent orgs (Strep viridans) assoc w/ dental proceduresii. Only infects damaged valvesiii. Most commonly mitral/aortic valves iv. Less destruction/less complications/less likely to cause septic infarction than acute infectionsv. Common finding is granulation tissue at the base of the vegetation

c. Predispositions = congenital heart defects, prosthetic valves (coagulase neg Staph epidermidis), IV drug use, catheters4. Non-bacterial thrombotic endocarditis (NBTE)

a. Sterile vegetation of fibrin/plts which do not directly cause valve damage (underlying tissue is normal)b. Form nodules along the line of valve closure (similar to rheumatic fever), valve doesn’t have to be damaged for this to occurc. Most commonly aortic/mitral valvesd. Don’t usually bother the valves but can throw emboli that cause infarctse. Predispositions = hypercoagulable states (think cancer pts), chronic diseases (think SLE, RA)

i. Libman-Sacks Endocarditis is assoc w/ SLE1. Vegetations on AV valves, chordae tendinae, or endocardial surface2. Thrombi adherent to areas of subendocardial fibrinoid necrosis/inflammation

ii. Carcinoid Heart Dz1. Pts have carcinoid syndrome w/ wheezing, flushing, diarrhea due to 5HT released from abnormal

neuroendocrine cells2. Endocardium of R heart thickened by accumulation of MPS-rich matrix w/ SM cells3. L heart protected b/c 5HT is metabolized in the lungs

5. Prosthetic valvesa. Bioprosthetic (from pig) eventual deterioration of tissueb. Mechanical (man-made) thrombi, hemolysis (metal parts cause sheer stress)

6. Clinical manifestations of endocarditisa. Most common presentation:

i. Fever (possibly low and intermittent; present in 90%) 1. Suspect IE if fever present ˃1wk

ii. Murmurs (can be new, or a change in current)1. Always regurgitation due to perforation/malcoaptation of valve2. Ring abscesses, chordal rupture, shunts contribute

iii. Acute onset CHF due to regurgiv. Bacteremiav. Embolization of veg (esp if >1cm) septic infarctvi. Constitutional sx like weight loss, night sweats, arthralgiasvii. *Various immune effects: petechaie, splinter hemorrhages (nail beds), Osler nodes (painful) and Janeway lesions

(non-tender) on palms/soles, Roth spots (retinal hemmorage white center)viii. Pericarditis

b. ECHO is gold standard to ID vegetation, a negative ECHO essentially rules out IEc. Dx requires combination of major/minor criteria to make definitive diagnosis

i. MAJOR: 2 positive blood culture, positive ECHO, new regurgitationii. MINOR: fever, predisposing cardiac condition, IV drug use, vascular sx*, immunologic sx*

1. Definitive IE = 2 major OR 1 major/3 minor OR 5 minor + histologic evidence from vegetation/emboli2. Possible IE = 1 major/1 minor OR 3 minor3. Negative IE = no histological evidence, resolved sx <4d w/ antibiotics, better explanation

d. Tx aims to sterilize vegetation through high [ ] of Abx

19

i. Low virulence = 2wk IV Abx ; high virulence = 4+wk IV Abx1. Amoxicillin or Clindamycin

ii. May need surgery if fungal endocarditis (Abx barely effective), abscess (no access), uncontrolled infxniii. Prophylaxis for various procedures (e.g. dental work) if have predisposing factors (congenital, prosthetic, prior IE)

1. MVP w/ MR is NOT an indication for prophylaxis

PERICARDITIS1. Definition

a. Inflammation of the pericardial surfaces, assoc with inflammatory infiltrate and fibrin exudateb. If pericardial pressure rises, the cardiac chambers may become compressed impaired ventricular filling decreased COc. Small amounts of fluid accumulated rapidly is usually worse than large amounts accumulated over time b/c tamponade

2. Acute Pericarditis (pericardium is actively inflamed)a. Primarily secondary to bacteria, viruses, TB, autoimmune (lupus, RA, Dressler’s), uremia/renal failure (accumulate slowly so

can see HUGE effusions), malignancy (breast, lung, lymphoma most common), radiation, drug inducedi. Serous pericarditis, causes = noninfectious, thus scant inflamm cells seen in exudates

1. Closest one to a transudateii. Fibrinous pericarditis (most common), causes = acute MI, Dresslers (occurs wk-mo post-MI), uremia/renal failure,

SLE/RA (AI attack on heart), radiation1. There is enough vascular permeability that fibrinogen leaks out (“bread and butter”)2. Moderate # acute inflammatory cells associated w/ eosinophilic fibrinous exudates3. Gives characteristic friction rub

iii. Suppurative pericarditis, causes = bacteria, thus tons inflamm cells seen in exudates + pus1. See creamy white/yellow fluid and granular hyperemic pericardial surfaces2. Commonly leads to constrictive pericarditis (chronic)

iv. Hemorrhagic pericarditis, causes = metastatic malignancy w/ angiogenesis, TB, bleeding disorderv. Caseous pericarditis, causes = TB (usually only in AIDS pts)

1. See foci of crumbly white material w/in pericardial surfaces (necrotizing granulomas)b. Clinical signs/Sx

i. Chest pain (palliative to lean forward), fever, tachycardia, dyspneaii. Loud friction rub

1. 3 component scratchy sound: mid-systolic (vent contraction), mid-diastolic (rapid vent filling), late diastolic (atrial contraction)

iii. EKG changes = ST elevation in all leads except aVRiv. Potential lab changes = ↑WBC count, ESR, CK-MB and troponin

c. Tx w/ NSAIDS, steroids, colchicine (anti-inflamm alkaloid)3. Chronic pericarditis

a. Adhesive pericarditis (common following serous or fibrinous acute pericarditis)i. Residual strands of CT b/w visceral/parietal pericardial surfaces

b. Soldier’s Plaques = focal firm collagenous thickening of pericardium that become calcifiedc. Constrictive pericarditis (common following suppurative or caseous acute pericarditis)

i. Pericardial space replaced by shell of dense fibrous/fibrocalcific CT that impairs diastolic fillingii. Chronic inflamm + fibrosis thickening/adherence to mycocardium calcification limited diastolic filling ↓CO

iii. Most common etiology is post-cardiac surgeryiv. Present with signs of right heart failure (JVD, hepatomegaly, peripheral edema)

1. Kussmaul’s Sign = inspiratory ↑ in JVP2. Pericardial Knock (early in diastole)3. Fatigue/hypotension/tachycardia

v. If calcified, may require pericardiectomy where peel calcified tissue off of heart (10% die during surgery)d. Adhesive mediastinopericarditis, causes = radiation/surgery involving mediastinum or suppurative or caseous pericarditis

i. Adhesion of parietal pericardium to mediastinum/surroundings ↑ cardiac workload hypertrophy/dilatation4. Cardiac tamponade

a. Dependent on both the rate and volume of fluid collectionb. Rise in pericardial pressure and compression of cardiac chambers in diastole impaired diastolic filling decreased COc. Clinical signs/sx

i. Hypotension, reflex tachy, shockii. Pulsus paradoxicus – accentuated RA filling during inspiration substantial decrease in LA volume (bulging

through IV septum) exaggerated lowering of systolic blood pressure (>10mm)iii. JVD/hepatomegaly/ascites/edema due to augmented venous return with compression of right heart

d. Tx = pericardiocentesis5. Pericardial effusions

a. Usually serous effusion that slowly fills the pericardium (slow enough not to impair diastolic filling)b. Common in renal or heart failurec. Clinical signs/sx

i. ECHO positive for fluid in pericardiumii. Muffled heart soundsiii. Ewarts sign (dullness, decreased breath sounds, and egophony over left posterior lung due to compression by the

enlarged pericardial sac)iv. EKG changes = alternating hi/lo QRS complexes due to heart “swinging” back and forth in fluid

20

6. Cardiac tumorsa. Primary tumors (usually benign)

i. Myxoma (most common cardiac tumor in adults)1. Can be familial assoc w/ Carney syndrome which is autosomal dominant2. Most commonly affects the LA (then RA), usually w/ a single polypoid gelatinous mass that can

obstruct/injure valves, embolize, and/or release cytokines3. Tumor is minimally cellular w/ scattered small spindle cells and stellate cells w/in myxoid matrix

ii. Rhabdomyoma (most common cardiac tumor/hamartoma in kids)1. Bulging intra-myocardial mass that can cause obstruction2. Characteristic large polygonal cells w/ central nuclei, intracellular vacuoles, and radiating bands of

eosinophilic cytoplasmiii. Papillary fibroelastoma

1. Myxoid fibrillary processes on “uptstream” surface of valve (looks like Alien face-sucker); can embolizeb. Secondary tumors (malignant)

i. Direct tumor spread leading to:1. Metastasis

a. Pericardial/epicardial surfaces see hemorrhagic effusion and cardiac constrictionb. Myocardium metastases w/in muscle can disrupt electrical signals

2. Vascular obstructiona. SVC syndrome where SVC obstruction leads to congestion/edema of head/neck/armsb. IVC syndrome where IVC obstruction leads to ↓ venous returnc. Pulmonary emboli can lead to impaired RV output

ii. Tumor-derived mediators1. NBTE can be due to mucinous adenocarcinoma2. Carcinoid heart dz due to 5HT in circulation (R heart)3. Amyloidosis due to excessive Ig production

21

CONGENITAL HEART DISEASE (CHD)1. Caused by defective heart development in 1st trimester and is most common birth defect

a. Common in chromosomal d/o i. 40% of trisomy 21 (Down) kidsii. 20-40% Turner (single X female)iii. 80% Trisomy 13 (Patau)iv. 93% Trisomy 18 (Edwards)v. 50+% DiGeorge (Ch21)

2. VSD is most common CHD followed by patent DA and Tetralogy of Fallot (TOF)3. Fetal Circulation

a. Fetal circulation usually prevents sx until after birthb. Placenta is the oxygenating organ and umbilical vein is most highly oxygenatedc. Fetal shunts – prevent blood from entering highly constricted pulmonary vascular bed

i. Ductus venosus (DV) – allows 50% of blood in umbilical v to bypasses the liver and enter IVC insteadii. Foramen ovale (FO) – allows blood in RA to bypass the lungs and enter LALVaorta instead (goes to heart/brain)iii. Ductus arteriosus (DA) – allows small amt of blood in pulm a to bypass the lungs and enter aorta (goes to

splanchnic/limbs)d. Transitional circulation

i. First breath expands lungs and its vasculature – b/c lower resistance, blood flows into lungs and shunts closeii. Clamping umbilical leads to regression of DV

4. Clinical Consequencesa. Congestive heart failure (L R shunts)

i. CO cannot meet needs of the bodyii. Mostly due to abnormal distribution of CO (b/c of shunt) but can be due to poor LV functioniii. Sx: feeding intolerance (this is exercise to infant), failure to grow, respiratory infections, dyspnea and fatigue

iv. Signs of CHD heart failure:1. Tachypnea (indicates pulmonary edema)2. Tachycardia (indicates SS activation trying to increase CO)3. Hepatomegaly (indicates RAS activation fluid retention, trying to increase SV)4. Do NOT usually see JVD or peripheral edema

b. Cyanosis (R L shunts)i. Easier to detect cyanosis at higher Hgb levels

1. 2 g/dL deox-Hgb normally in systemic arterial blood2. Need additional 3 g/dL deox-Hgb to detect cyanosis3. If have higher Hgb level (g/dL), that 3 g/dL is a lot smaller percentage of the total Hgb, and smaller

percentage changes in oxygen saturation are easier to detect than large percentage changesii. Signs of CHD cyanosis:

1. Clubbing (hypoxia stimulates VEGF more capillaries)2. Cerebral absesses/stroke (R L shunt bypass filtering ability of lung)3. Polycythemia (increased RBC in attempt to increase O2)

c. Pulmonary vascular disease (L R shunts)i. Inc pressure and flow intimal hyperplasia/vessel narrowing by 12-24 monthii. Eventually damage is irreversible increase PVR, once it exceeds SVR, switches to R L shunt (Eisenmenger’s)iii. Signs of CHD-induced pulm vascular disease: exercise intolerance, strokes, pulmonary hemorrhage

5. Classificationa. Left to Right Shunts (PDA, ASD, VSD)

i. Pulmonary flow exceeds systemic flow1. As PVR ↓ over 1st 6 wks of life, the difference b/w SVR and PVR ↑ and more blood crosses the L→R shunt

↑ volume to lungs ↑ volume to LA/LV LA/LV dilatation w/ ↑L heart DBP + pulm congestion/edemaa. pulm vasculature remodeling if pulm HTN allowed to persist

2. Loss of ox blood to R heart abnormally distributed CO that is perceived as “low” CO compensation via RAS activation fluid retention systemic congestion (remember: tachy-pnea/cardia, hepatomegaly)

ii. VSD = most common1. severity is due to size of defect and degree of pulmonary vascular resistance2. signs/sx:

a. Poor feeding, growth impairment, triadb. Loud S2 due to pulm HTNc. Holosystolic murmur (due to VSD) + diastolic murmur (due to ↑ flow across mitral valve)

i. Loudness of murmur inversely related to defect size b/c small defects = more turbulence3. surgery often required or will eventually lead to Eisenmenger’s if untreated

a. pulm HTN leads to remodeling of pulm vasculature ↑PVR until PVR exceeds SVR and direction of shunt switches to R→L (usually by teenage yrs w/o Tx)

b. Note, however, that 1/3 of VSDs have spontaneous closureb. Obstructive Lesions

i. Elevation of pressure proximal to the obstruction hypertrophy → hypertrophic ventricle will eventually failii. Coarctation of the Aorta (CoA) = most common

1. obstructive thickening of aortic wall >50% (a problem once ductus closes & blood can only go down aorta)

22

2. usually near/distal to left subclavian a3. signs/sx:

a. HTN proximal to coarctation (think: right arm HTN) + normal/↓ blood pressure in legsb. Collaterals often develop to bypass obstruction systolic murmur hear over spine

iii. Infant CoA syndrome = severe obstruction leads to acute LV failure (thus no time for hypertrophy)1. see gallop rhythm, pulm edema, weak pulses, mottled skin, possible cardiogenic shock w/

tachy-pnea/cardia and hepatomegalyc. Right to Left Shunts (ToF, tricuspid atresia, truncus arteriosus)

i. Systemic flow exceeds pulmonary flow 1. deox blood in systemic circulation cyanosis2. bypassing of lungs and their filtering emboli to brain

ii. Tetralogy of Fallot = most common1. severity is proportional to degree of RV outflow obstruction (deox blood will take path of least resistance)2. signs/sx:

a. RV outflow obstructionb. RVHc. Large VSDd. Overlying/overriding aortae. Holosystolic murmur (due to VSD) + systolic murmur (due to RV outflow obstruction)f. Single S2 (VSD equalizes pressure so aortic/pulmonic valves close simultaneously)g. Cyanosis does NOT respond to O2 therapy

3. Hypercyanotic spells (Tet spells)a. ↑PVR or ↓SVR causes sudden ↑ in R L shuntingb. Causes significant cyanosis syncope

d. Transpositioni. Great vessels arise from improper ventricles improper oxygenation/cyanosisii. Unlike RL shunts, amt pulm blood flow has no effect on degree of cyanosis depends on adequacy of mixingiii. Not compatible with life unless mixing can occur

1. best = FO or ASD, reliable b/c low pressures on both sides permit bi-directional shunting/minimal cyanosis2. PDA/VSD help some, but low resistance of pulm circulation favor blue blood to lungs, not red blood to aorta

iv. signs/sx: cyanosis from birth, tachypnea, poor feeding, corresponding murmur, single S2, metabolic acidosis

CARDIOMYOPATHY1. Results from a primary abnormality in myocardium2. Dilated Cardiomyopathy (DCM; most common):

a. Gradual degeneration of myocytes four chamber dilation w/ reactive hypertrophy (globoid heart) + systolic dysfxni. Extensive dilation stretches valve annulus mitral regurg, also predisposes to mural thrombi b/c of hypokinesisii. Very low contractility/EFiii. Histologically see non-specific myocyte atrophy/hypertrophy + fibrosis

b. True DCM is idiopathic, but similar clinical pic from EtOH, genetic (AD, cytoskeletal proteins), drugs (adriamycin), pregnancy, viral

i. Viral form is aka myocarditis1. Inflamm (esp. lymphocytes) is primary cause of cell degeneration

a. See soft mottled myocardium w/ normal to dilated chambers and sometimes mural thrombi2. 1˚ Coxsackie B, but can be due to other orgs (ex) diphtheria, in which exotoxin causes myocarditis3. Tend to be acute/self-limiting/subclinical (assoc w/ persistent viral genome in myocytes), rarely fulminate4. Other forms = sarcoidosis, drug hypersensitivity rxn (lots eosinophils), SLE

ii. Arrhythmogenic RV cardiomyopathy characterized by replacement of RV myocardium w/ fat/fibrous tissue leading to R-sided heart failure and arrhythmias

3. Hypertrophic Cardiomyopathy:a. Massive LV hypertrophy (“banana-shaped” LV cavity) small LV/impaired relaxation diastolic dysfxn

i. High contractility but low SV due to inadequate pumping (uncoordinated LV contraction)ii. Histologically see myofiber disarray (poorly conduct, which predisposes to arrhythmias)iii. See sub-aortic stenosis due to opaque white endocardial thickening in sub-aortic region (systolic ejection murmur)

b. Usually 1˚ familial (AD, sarcomere proteins), cause of death in young athletes4. Restrictive Cardiomyopathy:

a. Subendocardial fibrosis/infiltration by substance firm myocardium w/ normal/↑ thickness of ventricle wall low LV compliance diastolic dysfxn

i. Contractility is normal but low SV due to inadequate fillingii. Characteristic is Kussmaul’s sign (loss of the normal variation in JVD due to inspiration)iii. Histologically see amyloid, iron, glycogen vacuoles

b. Due to amyloidosis (Congo red), hemachromatosis, or glycogen storage dz whose accumulated substances stiffen hearti. Senile cardiac amyloidosis (amyloid from transthyretin)ii. Systemic amyloidosis (AL amyloid from Ig light chains and AA amyloid from serum amyloid-assoc prot)iii. Isolated atrial amyloidosis (amyloid from atrial natriuretic peptide)

23

HEART FAILURE1. CHF is dz of elderly, most common cause is ischemic heart dz due to coronary atherosclerosis, also most # of hospitalizations2. Heart cannot pump enough blood to meet bodies demand circulatory failure, most commonly due to myocardial failure

a. Myocardial Dysfxni. Systolic failure (2/3 cases): impaired pumping due to loss of muscle mass (i.e. postMI) low EF

1. Need greater preload (higher EDV) to increase SV and maintain CO (Frank-Starling) infarcted tissue thins LV dilation stretches annulus mitral regurgitation

a. Positive inotropic agent (ie catecholamines)= results in upward shift of Frank-Starling curve such that ↑CO achieved for given EDV (see downward shift of curve w/ CHF)

2. Increased EDV is transmitted back to LA, lungs (pulm edema), RV (RV failure mostly due to LV failure)3. Other causes = EtOH (damages contractility), adriamycin, cocaine, hypothyroidism, myocarditis

ii. Diastolic failure (1/3 cases): abnormal relaxation due to stiff LV (i.e. hypertrophy), but EF preserved1. Need greater pressure than normal to eject a given preload2. Sx dramatically worsened due to:

a. Ischemia (low O2), since relaxation is an ATP-dependent processb. Elevated heart rate since the duration of diastole (filling time)

3. Causes: severe HTN, hypertrophic cardiomyopathy, amyloidosis/hemochromatosisa. Sx of HCM: DOE, syncope, a-fib, S4, systolic murmur that increases w/ Valsalva

iii. Cor pulmonale: increased pulm vascular resistance due to lung dz RV failure1. ↑ R EDV is transmitted back to systemic venous circulation JVD, hepatomegaly, pitting edema2. Left heart typically unaffected, unless compressed by large RV3. Causes: fibrosis, silicosis, COPD, PE4. Oxygen therapy to dilate pulm arterioles helps by easy strain on RV

b. High Output Failurei. AV fistula (bypasses capillary bed) ↓ resistance, so in order to maintain BP/perfusion, CO increases dramaticallyii. Some of CO circulates through low resistance AVf thus reducing CO to other organs = circulatory failure

c. Dysrhythmias: chronic, inappropriate elevation of heart rate (atrial fib, flutter) or uncoordinated contractiond. Pericardial Disease: normally pliable, but in tamponade/constrictive pericarditis it stiffens restricted pumping/fillinge. Valvular Dysfunction: either regurgitation/stenosis circulatory failure

3. Hemodynamica. In CHF, problem is inadequate CO +/- pulm congestion various stages of warm/cool, dry/wet, etc.b. Frank-Starling curve shows CHF heart w/ lower contractility, lower EF

4. Neurohumoral: overall, NOT helpfula. Sympathetic increased HR/contractility (β1) + VC (1)

i. Elevated levels long-term increase mortality, but catechols are necessary evils – the increased HR/contractility helps maintain CO/BP but also ↑O2 demand, the VC helps maintain BP but also increases afterload to a failing heart

b. RAS angioII VC + Na retention + SS activation (aldosterone contributes to these effects)i. Same as above, it works to maintain BP but over time will only worsen the failure due to increased afterloadii. Renin released due to decreased CO/renal perfusion, decreased Na @ macula densa, 1 SS stimulationiii. angioII is growth factor leading to cardiac myocyte hypertrophy

c. BNP (brain natriuretic peptide) VD + ↑ Na excretion + ↓renin secretioni. Elevation is highly sensitive/specific test for heart failureii. Works to ↓ afterload, but VD decreases resistance/BP which forces failing heart to pump harder for sufficient CO iii. Normally effects are outweighed by RAS

5. Clinical presentationa. Low CO fatigue, DOE, cool skin, increased BUN:Cr ratio (due to low renal blood flow)b. Pulmonary edema SOB, orthopnea, PND, cardiac asthma, rales, S3c. LV dilation laterally displaced PMI, cardiomegaly on CXR, holosystolic murmur (MR)d. RV failure JVD, hepatomegaly, pitting edema, (+) hepatojugular reflex, elevated LFTs (due to hepatic congestion)e. Other Labs: hypoNa/hypoK (normally induced by therapy, ex: diuretics), high BNP

6. Tx: See pharm chart below, also bed-rest (↓ workload/catechol release + leg elevation = spontaneous diuresis), low Na diet (reduces Na and water retention)

24

PHARMACOLOGY1. HTN

a. Normal <120/<80, PreHTN: 120-140/80-90, Stage 1 HTN: 140-160/90-100, Stage 2 HTN: >160/>100b. Goals: HTN alone <140/90, diabetes/renal dz <130/80, LV dysfxn <120/80c. Commonly 1st line: thiazides, beta blockers, ACE (-), Ca channel blocker (if A-fib)

DIURETICS MOA Place in Therapy Clinical Pearls

Thiazides HCTZ Chlorthalidone

Blocks Na reabsorption in DCT DOC in isolated mild systolic HTNPreferred in AA ptsLess effective in RF

SE: hypoK, hypoTN, acute renal failure-ARF*, DM, goutdecrease stroke/MI

*decreased perfusion due to hypovolemia

Loop DiureticsFurosemideTorsemide

Blocks Na/Cl reabsorption in LOH excessive vol loss

Uncommon for HTNUsed in RF (Cr<20)

SE: hypoK, hypoTN, ARF, hypoMg, ototox

Potassium Sparing

TriamtereneAmiloride

Blocks Na reabsorption in CT/CD less K lost in urine

Adjunctive therapy to prevent hypoK

SE: hyperK caution w/ chronic renal insufficiency, or any situation w/ high K (supplements, salt substitutes)

ANTI-ADRENERGICSMOA Place in Therapy Clinical Pearls

Beta-BlockersMetoprololAtenololCarvedilol

Block cardiac β1 R ↓ HR ↓ CO ↓ BP

Use w/ concurrent heart dzDOC for hypertrophic CMMay not be as effective in AA

SE: bradycardia (caution w/ EF <40%), hypoTNcontraindicated in asthma (metoprolol best)may mask hypoglycemia in DMdecreases mortality

Alpha-BlockersTerazosinPrazosinDoxazosin

Block vascular R VD ↓ resistance ↓ BP

Uncommon due to hypoTNUsed if uncontrolled despite other meds

SE: hypoTN, orthostatic hypoTN, syncopenever use as monotherapy

RAS INHIBITORSDrug MOA Place in Therapy Clinical Pearls

ACE (-)LisinoprilCaptoprilRamipril

Blocks Ang I Ang II, thus blocking VC (↓ afterload) and Na retention (↓ preload)

1st line tx due to many compelling indications (heart failure, DM, CAD)DOC for heart failure

SE: acute renal failure, cough, angioedema, hypoTN, hyperK (monitor creatinine & K)decreases mortalityafter MI prevents remodeling

*decreased GFR due to dilation of efferent arteriole ANG II R Blockers

ValsartanLosartan

Blocks Ang II receptor same effects as above

Used if ACE (-) can’t be SE: similar to ACE (-) but no coughMore $

Aldosterone AntagSpironolactoneEplerenone

Comp antag of aldosterone R prevention of Na retention

Limited role SE: hyperK (K-sparing), ARF, gynecomastiaRenal clearance

Renin (-)Aliskiren

Inhibits renin to block conversion of angiotensinogen→ ang I

Newer drug, unknown SE: hyperK

VASODILATORSDrug MOA Place in Therapy Clinical Pearls

Ca Channel Blockers

Amlodipine (di)Nifedipine (di)Diltiazem (non)Verapamil (non)

Block L-type Ca channels decrease Ca influx into vascular SM cells VD

DHP: ↓ BPnon-DHP: ↓ BP AND HR

non-DHP often DOC in A-fib

SE: bradycardia (non), periph edema/hypoTN (di)constipation (verapamil)

Clonidine 2 agonist 3rd line Rebound HTN with abrupt discontinuation (taper)Hydralazine Direct vasodilator 3rd line Requires 3x/day dosing

Can induce drug-induced SLE-like rashMinoxidil 3rd line Orthostasis, reflex tachycardiaNote: di = dihydropyridines (DHP), which are vasodilators

non = non-dihydropyridines (non-DHP), which VD and ↓HR

25

2. CAD – goals of therapya. inhibit platelet aggregation = aspirin, clopidogrelb. reduce myocardial O2 demand = β-blockers, Ca channel blockersc. increase myocardial O2 supply = nitrates, Ca channel blockersd. prevent plaque formation/reduce lipid levels = Statinse. lower overall CV risk = ACE (-), ARBs, Eplerenone

INHIBIT PLATELET AGGREGATIONDrug MOA Place in Therapy Clinical Pearls

Aspirin Irreversible (-) of COX less TXA2 less plt activation

Secondary prevention for all pts with CAD and DM

SE: bleeding, GI decreases mortality post-MI

ClopidogrelTiclopidinePrasugrel

Block ADP receptor irreversible for life of plt

Used in pt w/ ASA allergyUsed in combo w/ ASA following acute coronary syndrome

SE: bleeding (risk double w/ ASA combo)Given prior to percutaneous intervention then continued for 3-9moStop 5-7d prior to invasive surgery

DECREASE MYOCARDIAL O2 DEMANDDrug MOA Place in Therapy Clinical Pearls

Beta-blockers Block cardiac β1 R ↓ HR/contractility ↓ 02 demand ↓ ischemia

DOC stable anginaALL post-MI pts

SE: bradycardia (caution w/ EF <40%), hypoTNcontraindicated in asthmamay mask hypoglycemia in DMdecreases mortality post-MI

Ca Channel BlockersNON-DHP ONLY!

Block L-type ↓ Ca influx ↓ HR/contractility ↓ O2 demand ↓ ischemia

Use if contra to β-blockerAdjunct to β-blocker

SE: bradycardia, constipation (verapamil)

INCREASE MYOCARDIAL O2 SUPPLYDrug MOA Place in Therapy Clinical Pearls

NitratesNTGIso mononitride

Exogenous source of NO VD ALL stable angina pt should have SL NTG for rescue

SE: headache, hypoTN

Ca Channel BlockersBOTH DHP/NON!

Block L-type ↓ Ca influx VD ↑ blood flow ↑ O2 supply

Use if contra to β-blockerAdjunct to β-blocker

SE: above + peripheral edema, hypoTN

REDUCE LIPID LEVELSDrug MOA Place in Therapy Clinical Pearls

StatinsSimvastatinAtorvastatinRosuvastatinPravastatinLovastatin

Inhibits HMG-CoA reductase thus preventing synthesis of cholesterol lowers LDL

Tx to goal LDL in “30s” Hi risk CAD <70 CAD/DM <100 No CAD/DM+2RF <130 No CAD/DM+1RF <160

SE: rhabdomyolysis/myopathyCYP3A4 system many DDIdecreases mortality in ACS

Start Tx when pt is 30 pts above their goal valueRFs: smoking, HTN, low HDL, family hx, age

LOWER OVERALL CV RISKDrug MOA Place in Therapy Clinical Pearls

ACE (-) See above decreases mortality in post-MI/CADAngiotensinRBlock Self-explanatory Use if s/e to ACE (-) decreases mortalityEplerenone Aldosterone antag decreases mortality in post-MIRanolazine indirectly prevents Ca

overload less ischemiaStill undefined used in refractory stable angina

Case148y African American F, no PMHBP = 150/90 (Stg 1), SCr = 1.5, K=4

No compelling indications + AA + cheap/easy = HCTZCase 248y African American F, DM/CKD/HTN, currently on clonidine/HCTZ/glyburideBP = 180/100 (Stg 2), CHECK Cr/K

Hi BP most likely due to abrupt discontinuation of clonidine rebound hypertensionDM/CKD = compelling indications for ACE (-), can also add beta blocker/aspirin

Case 365y Caucasian M, DM/stable angina/HTN, currently on HCTZBP = 140/90 (Stg I), CHECK Cr/K (…remember - goal for BP should be <130/85 due to diabetes)

DM/stable angina = compelling indications for beta blocker, aspirin, ACE (-), SL NTG for rescueShould check lipid panel, since high risk pt (due to DM/angina) want <70 LDL, consider adding statinIf BP still not controlled, can add renolazine

3. ACUTE CORONARY SYNDROMES/ATRIAL FIBRILLATION

26

ANTI-THROMBOTICSDrug MOA Place in Therapy Clinical Pearls

UFH Enhances action of antiTHB3 inactivation of IIa/IXa/Xa

NSTEMI, STEMI SE: HIT ( 50% decrease in plts)Peak effect w/in minutesPrevent new thrombi but NO lysis of existing thrombi

LMWH Same but more specific for Xa NSTEMI, STEMI SE: less chance of HITEliminated renally

Fondaparinux Direct Xa inhibitor Prevent DVTIf get HIT w/ heparin

No monitoring/dosed daily (predictable); low HIT riskInactive against preformed IIaRenal clearance

Bivalirudin Direct thrombin (-) If get HIT w/ heparin (-) both free and fibrin-bound thrombinThrombolytics

tPAstreptokinase

Convert plasminogen plasmin clot lysis

STEMI (vessel totally occluded & need to dissolve the clot)

Used mostly now for stroke (w/in 3h) and STEMI pt where percutaneous intervention no readily available

Note: Blocking 1 molecule of Xa will block ~50 molecules of IIa

ANTI-PLATELETSDrug MOA Place in Therapy Clinical Pearls

ASA Irr (-) COX no TXA2 no plt activation

Pretty much all heart probs SE: GI sx, bleedingDecreases risk of another MI by 20%

Clopidogrel Irr (-) ADP R no activation If allergic to ASAGP IIb/IIIa antag

AbciximabEptifibatide

Prevent plt aggregation by blocking fibrinogen x-linking

STEMI (abciximab)NSTEMI (eptifibatide)

Both have t½ ~2.5h

ANTI-COAGULANTSDrug MOA Place in Therapy Clinical Pearls

Warfarin Prevents synth of vit K-dep factors II/VII/IX/X via VKOR inhibition/lack of oxVitK recycling

a-fib + any high risk factor* DVT or PE

SE: bleeding (esp. intracranial), anaphylaxis (IV)Use low dose IV AND oral Vit K to reverseLong t1/2, hard to dose, check INR frequentlyTakes ~48h for peak effect (10+d to Css)DDIs w/ cyp2C9/3A4 users

ASA As above a-fib but no risk factors and <65yo

*note: risk of ischemic stroke is 2x greater in a-fib, CHADS2 Score gives stroke risk based on co-morbities (CHF, HTN, DM, TIA, age˃75) ----3+ of the 5 CHADS risk factors makes pt good candidate for warfarin due to high risk of stroke

4. HEART FAILURE(Refer to previous charts for more drug data)

27

a. Classes based on sx (go back one if sx improve) vs stages based on LV fxn (CHF is progressive, thus can only get worse)i. Normalii. 1 – Asymptomatic w/ LV dysfunction = ACE(-), ARBsiii. 2 – DOE w/ compensated CHF = diuretics, b-blockersiv. 3 – Limited physical activity w/ decompensated CHF = increased diuretics, spirnolactone, digoxinv. 4 – Bedridden w/ refractory CHF = inotropes, vasodilators, transplant

b. Drugs that may hurt CHF ptsvi. Diltiazem and Verapamil are only safe when treating diastolic failurevii. Flecainide and Moricizine are antiarrhythmics that can kill CHF ptsviii. Prazosin just doesn’t have any benefit

CHRONIC MGMT (compensated CHF)Drug MOA Place in Therapy Clinical Pearls

ACE(-) Block angiontensin II formation and bradykinin degradation (VD)

DOC for CHF (even Asx) SE: hyperK, dry coughdecreased mortality, slows progression

ARBs Block angiotensin II receptor AT1 If ACE(-) not tolerated SE: hyperKdecreased mortality

Diuretics (1˚ loop)

↓ volume less congestion Symptomatic relief only SE: hypoK, hypovolemia

Spironolactone Aldosterone R blocker Class III-IV CHF SE: hyper Kdecreased mortality

Digoxin Cardiac glycoside which blocks Na-K ATPase pump increase LV EF, CO, exercise capacity

If CHF still poorly controlledPositive inotropic agent

DDI: Amiodarone (↑ [dig])

SE: bradycardia, arrhythmias, hyperK, halosGI/CNS tox may be 1st sign of toxNO loading dose, NO correlation b/w dose/efficacyRenally excreted, MUST watch renal fxn

b-blockersMetoprololCarvedilol

Increases density of b1 R, (-) cardiotox of NE/Epi, decreases neurohormonal activation

Adjunct to ACE (-) SE: hypoTN w/ other antiHTNs, bradycardia w/ digdecreased mortalitymust titrate slowly to prevent CHF exacerbation

Nitrate (vein)+ hydralazine (art)

Venous VD decreased preload + arterial VD decreased afterload

If ACE(-) not toleratedAA pts as adjunct to ACE(-)

SE: hypoTN and reflex tachycardiadecreased mortalityincreased exercise capacity

ACUTE MGMT (decompensated CHF)Drug MOA Place in Therapy Clinical Pearls

Dobutamine β receptor agonist (β1 ↑ cardiac contractility, β2 ↓ BP)

Emergency IV inotrope/chronotrope improve sx and are only temporary (e.g. use while waiting for transplant)

Milrinone PDE(-) no breakdown cAMP increased muscle contract

Emergency Positive inotropeCauses peripheral VD

Nitroglycerine VD (↓preload) HTN emergencyNitroprusside Nitrite bound to cyanide VD

(↓preload and afterload)HTN emergency Cyanide or thiocyanate toxicity

methemoglobinemiaNesiritide BNP analog Rarely used HypoTN; may increase mortality/renal failure

PRESSORS (SBP<90 w/o hypovolemia, i.e. cardiogenic/septic shock, SHORT TERM ONLY!!!)Drugs MOA Effects

Dopamine Low – dopamine receptorMed – dopamine/β receptorsHigh – dopamine/β/ receptor

Low VDMed β1 stimulation (↑ HR/contractility)High 1 stimulation (↑ SVR/BP/afterload)

Epinephrine β1, β2 stimulation ↑ CO/SVRNE stimulation ↑ SVRNote: Long-term catecholamine tx (including dobutamine, dopamine, epi, NE) leads to desensitization and receptor downregulation

OTHER Drugs MOA Place in Therapy Clinical Pearls

AmiodaroneDofetilideDronedarone

Antiarrhythmic CHF + atrial fibrillationAtrial fibrillationAtrial fibrillation and flutter CI in heart failure

Amlodipine AntiHTN/antianginal CHF + HTN/stable anginaWarfarin Anticoagulant CHF + CAD/afib/etc Efficacy not provenTolvaptan Vasopressin antagonist Correct hypoNa in CHF pt No impact on mortality

HIGH YIELD

Adriamycin Can cause drug-induced dilated cardiomyopathyAnterior infarction LAD, leads V1-V4

28

Aschoff bodies Dx nodules of rheumatic feverAtrial fibrillation NO S4!!!! Can’t hear sound that reflects atrial contraction if there IS NO atrial contractionBuerger dz Small/medium vasculitis of young male smokers C-ANCA Wegener’s granulomatosisCaravello’s sign holosystolic murmur that increases w/ inspiration, seen in tricuspid regurgitationChagas dz Infxn Trypanosoma that can lead to myocarditisCheyne-Stokes respirations Cyclic pattern of respirations w/ increasing breaths followed by apnea, seen in CHFCommissural fusion Dx of rheumatic heart diseaseConcentric hypertrophy Increased thickness:vol, due to pressure overloadCoxsackie B MyocarditisCystic medial degeneration Seen in Marfans pts w/ dissecting aneurysmDelta wave Shortened PR segment seen in Wolfe-White-ParkinsonDiastolic murmur, blowing decres Aortic regurgitationDiastolic murmur, rumbling Mitral stenosisDressler syndrome 2-10w postMI fibrinous pericarditis, due to autoAbEccentric hypertrophy Normal thickness:vol (both dilation & hypertrophy), due to volume overloadEjection click Aortic stenosisEisenmengers RL shunt that results from untreated LR shunt, see cyanosisEwarts sign decreased breath sounds in L post lung due to compression by enlarged pericardial sacFriction rub Fibrinous pericarditisGloboid heart Dilated cardiomyopathyHypercyanotic spells Seen in Tetralogy of Fallot, sudden increase in RL shunting causes cyanosis/syncopeInferior infarction RCA, leads LII, LIII, AVFJames bundle Accessory pathway in LGL = no PR interval w/ P-QRS-T right in a rowJaneway lesions Non-tender nodules in palms/soles, suggestive of infectious endocarditisKaposi sarcoma Vascular sarcoma seen in AIDS ptsKussmaul’s sign JVP increases w/ inspiration, seen in constrictive pericarditis and hypertrophic CMLateral infarction LCF, leads LI, AVLLewis index Height of LI R wave + depth of LIII S wave >25mm, + for LVHMid-systolic click Mitral valve prolapseOpening snap Mitral stenosisOsler nodes Tender nodules in palms/soles, suggestive of infectious endocarditisP-ANCA Microvascular polyangitisPulsus paradoxus Exaggerated decrease of SBP during inspiration (>10mm), seen in pericarditis/tamponadePulsus parvus et tardus Pulse is weak and later than normal, seen in aortic stenosisPVC a premature beat, hidden P wave + huge QRS + pause, due to ischemiaR on T PVC falls on middle of T wave, bad b/c ventricle is vulnerable to developing VTRoth spots Retinal hemorrhages w/ central white spot, suggestive of infectious endocarditisS3 Rapid ventricular filling, heard in CHF/mitral regurgS4 Atrial contraction into stiff LV, heard in AS/HTN/hypertrophic cardiomyopathySeptic emboli/infarct Acute bacterial endocarditisSick Sinus Syndrome SA node dysfxn + failure of all supraventricular automaticity foci bradycardiaSokolow index Height of V5 R wave + depth of V1 S wave >35mm, + for LVHSystolic murmur, harsh cres/decres Aortic stenosisSystolic murmur, holosystolic Mitral regurgitationTransition Zone +/- deflection of R wave is equal, usually at V3/V4

After 938575 hours of trying to figure out the murmurs w/ Chris, this is what we boiled it down to. I know it doesn’t actually make any sense, but I really don’t care anymore.

Aortic Stenosis Pure AS concentric LV hypertrophy Mitral Stenosis Pure MS eccentric LA hypertrophy, LV is unchanged

Dr. V’s 5 basic principles of regurg state: 1. “Regurg causes a volume overload of the chambers proximal and distal to the leaking valve.”2. “The atria/ventricles must pump the normal amount of blood plus the regurgitant blood increased preload.”3. “The response to an increase in preload is eccentric hypertrophy – both dilation and hypertrophy.”

THUS…Aortic Regurgitation Pure AR eccentric LV hypertrophy + systemic VD (i.e. the distal dilation)Mitral Regurgitation Pure MR eccentric LA AND LV hypertrophy