- Leading cause of death for all races in the US

- Higher rates for blacks and hispanics than whites

- Risk increases with age

- 55 of every 100,000 Americans die of CVD each year

- Huge economic cost too!!

- An attribute that is associated with disease occurrence after adjusting for other known risk factors

- Age, sex (male), family history (M<55 and F<65), and chromosome 9p2 mutation --> No methods for prevention

- Hypertension (<140/90), hypercholesterolemia, diabetes, inactivity, diabetes and smoking --> Useful methods from prevention are available

- Assessed since 1948 with the Framingham Heart Study

- Spouses generally develop CHD together --> Higher rates of women developing CHD when their husband has CHD

- Strength --> Represented with a large relative risk (RR)

- Consistency --> Confirmed for other populations

- Temporality --> Ability to establish which came first

- Biological gradient --> Dose-response relationship

- Plausibility --> Acceptable given current biological knowledge

- Coherence --> Consistent with other facts known about the disease process

- Experiment --> Animal/RCT consistent data

- Analogy --> Similar associations are causal

- Prevalence: Proportion of people in a population who have disease at a point in time --> Snapshot in time

- Incidence: Number of new cases developing disease in a population during a given time interval --> Over a period of time

- Higher rates of smoking in less educated individuals

- Most adult smokers started smoking before 18 years old

- Increased risk of CHD with increased smoking habit

- Health Consequences of smoking: Heart disease, stroke, dementia, vascular disease, cancer, chronic lung disease, adverse pregnancy outcomes, and impotence

- Intervention: Ask, Advise, Assist, and Arrange

- Smoking cessation: Weight gain, significant decrease in MI risk (1 or 1.1 RR after 2 years), 10 years of life gained when patient quit by age 30

- QUIT!!!

- ~3 sessions/week of vigorous activity for >20 min or ~5 sessions/week of light/moderate activity >30 min

- Men: 40% for whites, 36% for blacks, and 30% for Hispanics

- Women: 36% for whites, 24% for blacks, and 26% for Hispanics

- Increased fitness leads to reduced RR for CVD and mortality

- 70% of US is considered sedentary (<30 min of activity/week)

- Increased prevalence in the US --> Primarily in southeastern states

- Women: RR of 3.8 with diabetes for CVD

- Men: RR of 2.0 with diabetes for CVD

- Worse to have diabetes as an obese woman in regards to CVD risk!!

- Diabetes treatment --> Decreases lipid levels and slows progression of microvascular disease

- Increased total cholesterol and LDL levels --> Increased RR for CVD

- Decreased HDL --> Increased RR for CVD

- Total cholesterol: <200 (desirable), 200-239 (borderline), and >240 (high)

- LDL cholesterol: <130 (desirable), 130-159 (borderline), and >160 (high)

- HDL cholesterol: >35 (desirable), <35 (undesirable)

- Triglycerides: <200 (desirable), 200-400 (borderline high), 400-1,000 (high) and >1,000 (very high)

- Pancreatitis is really the only reason triglycerides get >1,000

- Chylomicrons: Exogenous triglycerides surrounded by AI, AII, AIV, and B-48 apoproteins

- VLDL: Endogenous triglycerides and phospholipids surrounded by B-100, CI, CII, CIII, and E apoproteins

- IDL: Esterified cholesterol and phospholipids surrounded by B-100 and E apoproteins

- LDL: Triglycerides and esterified cholesterol surrounded by B-100 apoprotein

- HDL: Phospholipids and cholesterol surrounded by AI, AII, CII, and E apoprotein

- B-48: Gut secretion/biosynthesis

- B-100: Liver secretion/biosynthesis

- CII: Activates lipoprotein lipase

- CI, AI, and AIV: Activates Lecithin:Cholesterol Acyltransferase (LCAT)

- D: Activates Cholesterol ester transfer protein (CETP)

- B-100 and E: Binds LDL receptor

- E: Binds remnant receptor

- AI and AII: Binds HDL receptor

- CI, CII, and CIII: Inhibits binding to hepatic E receptor

- Hyperchylomicronemia

- Deficiency in lipoprotein lipase --> Familial LPL or Apo CII deficiency

- Cholesterol levels are normal

- Triglycerides are greatly elevated

- Familial hypercholesterolemia (FH): LDL receptor deficiency

- LDL and total cholesterol levels are increased

- Normal triglycerides

- Patients develop premature CVD

- 1 in 1,000,000 occurance

- 1/500 gene frequency

- Tendinous xanthomas common

- Family Dysbetalipoproteinemia

- Increased cholesterol and triglycerides

- Incomplete catabolism of chylomicrons and VLDL particles

- Increased incidence of peripheral vascular disease or CVD

- 1/10,000 occurance

- Palmar xanthomas (yellow) common

- Familial Endogenous Hypertriglyceridemia

- Accumulation of VLDL in plasma --> Milky appearance

- Heterozygous incidence is 1%

- Triglycerides between 200 and 500 mg/dL

- Increased risk of premature CVD

- Accumulation of VLDL and chylomicrons in plasma --> Milky appearance

- Uncommon

- Triglycerides are >500 mg/dL

- Increased risk of diabetes

- Etiology not certain

- Every 5 years for all adults >20 years old --> Total cholesterol levels

- Obtain sample after >14 hour fast

- Screen for HDL in a setting of documented CVD or strong family history

- Evaluate for other CVD risk factors

- Physical Exam: Check for bruits and xanthomas

- Consultation: Talk with patient, repeat lipid profile, and rule out secondary causes

- Cholesterol: 200 mg cholesterol=8-10 mg/dL in serum

- Saturated fat: Every 1% of calories=2.7 mg/dL

- Weight reduction: Obesity is associated with increased triglycerides and reduction in HDL

- Soluble fiber: Helps keep you full!!

- Based upon LDL-cholesterol levels

- Initiation levels of LDL differ depending if patient has risk factors or CVD

- Drug therapy with CHD: LDL >130

- Dietary therapy with CHD: LDL >100

- LDL <100 mg/dL in patients with diabetes and vascular disease --> Goal for treatment is <70 mg/dL

- BMI >25: Overweight --> 64% of Americans

- BMI >30: Obese --> ~50% by 2025

- Obesity --> RR of 1.4 to 3.0 depending of severity of obesity

- Abnormal waist to hip ratio: M >0.9 and W >0.85

- Apple body type --> Higher obesity risk --> Central obesity/toxic waist

- Cardiovascular disease

- Sleep apnea

- Diabetes --> 60-70% are overweight

- Dyslipidemia

- Hypertension --> 80% are overweight

- Cancer

- Phlebitis/cellulitis

- Osteoarthritis

- Gout

- Gynecological abnormalities

- Gall bladder disease

- Liver steatosis

-~20% of children are now obese

- Childhood factors: Maternal obesity, low family income, high fat/calorie intake, and avid TV watching

- Adult factors: Maternal obesity, birth weight, and timing/rate of maturation

1. Hormones released

- Angiotensinogen --> Increases BP

- Free fatty acids --> Increased insulin resistance

- Plasminogen Activator Inhibitor --> Pro-thrombotic

- IL-6, CRP, and TNF --> Pro-inflammatory cytokines

- Adiponectin --> Decreases inflammation and increases insulin sensitivity

2. Association with diabetes --> Central adipose tissue specific

- Releases more angiotensinogen, FAs, PAIs, and cytokines --> Increased BP, insulin resistance, thrombosis, and inflammation

- Releases less adiponectin --> Increased inflammation and decreases insulin sensitivity

3. Large adipocytes are located around the trunk and small adipocytes are located around the butt and thighs

- ~Pre-diabetic state

- Need 3 of the 5 characteristics to qualify

- Twice the risk of CVD with metabolic syndrome

1. Abdominal obesity/Increased weight circumference (M >102 cm or F >88 cm)

2. Increased triglycerides (>150 mg/dL)

3. Low HDL (M <40mg/dL or F <50mg/dL)

4. Blood pressure (>130/>85 mmHg)

5. Fasting glucose (>100 mg/dL)

- 5% or 10% weight loss over 6 months --> Significant decrease in morbidity

- Decreased HbA1c, blood pressure, and total cholesterol

- Need at least 10% weight loss to make a real difference!!

- Increased HDL levels

- Decreased trigylceride levels only seen with 5-10% weight loss

- Inflammatory biomarkers: TNF, IL-6, P-selectin, ICAM-1 and VCAM-1 all reduced after 12 months

- Dieting: Specific diet doesn't matter, decreased caloric intake matters more

- Less than 1% of obese patients are prescribed meds for weight loss

- Phentermine: Amphetamine derivative --> Short term use (12 weeks) --> Do not use in children, hypertensives or CVD patients

- Orlistat: Lipase inhibitor --> Inhibits 1/3 of lipid absorption

- Topiramate/phentermine (Qsymia)

- Discontinued meds: Sibutramine, fenfluaramine/dexfenfluaramine (Fen-Phen), and cannaboid receptors

-Rimonabant (Endocannabinoid Med): Inhibit endogenous pleasure centers to reduce hunger --> Ended up causing unexpected suicides

- Most effective treatment for obesity --> Amount and duration --> Life changing intervention!!

- Indications: BMI >40 or BMI >35 with CVD risk factors

- Contraindications: History of non-compliance, pyschiatric illnesses, and surgical risks

- Roux-en-Y (gold standard) and adjustable gastric banding procedures

- Can lose 50-70% of weight --> Usually maintain about 20% weight loss due to decreased metabolic rate (survival mode)

- 29% reduction in risk of death after 10 years

- 80% of patients without diabetes afterwards --> Blood sugars stabilize within weeks!!

- Niacin --> Vitamin B3

- Recommended dose is 20 mg/day --> Treatment with >1 g/day

- Decreases triglycerides --> Decreases fatty acid release from adipose tissue and decreases hepatic VLDL synthesis and release

- Increased HDL cholesterol --> Decreased Apo A1 hepatic uptake

- Liver damage

- Cutaneous flush --> Prostaglandin mediated

- Gastrointestinal toxicity

- Gemfibrozil --> Activates transcription factor, PPAR-a

1. Decreases serum triglycerides --> Increased lipoprotein lipase activity and FA oxidation and decreased VLDL secretion from the liver

2. Increased serum HDL cholesterol --> Increased Apo AI and AII gene expression

3. Increased LDL receptor expression --> Small decrease in LDL cholesterol

- Cholestyramine

- Positively charged --> Bind negatively charged bile acids

1. Enhance hepatic conversion of cholesterol to bile acids

2. Increased clearance of LDL cholesterol from plasma

3. Increased hepatic expression of LDL receptors

- All help to reduce serum LDL levels

- Oral administration with negligible bioavailability

- Increased serum triglycerides

- GI side effects --> Constipation, impaired fat absorption and must not be taken with anionic drugs

- Other drugs should be taken either 1 hour before or 3 hours after

- Ezetimibe

- Inhibits intestinal cholesterol absorption via NPC1L1 transporter

- Reduces serum LDL cholesterol by 20%

- Often formulated with statins for additive decrease in LDL

- Reduces LDL cholesterol

- Does not reduce the plaque size 

- May increase cancer risk

- Less effective than niacin-statin combination therapy at reducing mean carotid intima-media thickness and CV events

- Selective and potent competitive inhibitors of hepatic HMG-CoA reductase --> Lowers LDL by 25-60%

- Small increase in HDL cholesterol and decrease in triglycerides

1. Increases expression of LDL receptor

- Increased activity of protease --> Releases sterol-regulatory-element binding protein from the ER --> Interacts with LDL gene --> Incorporates LDL receptor into hepatic membrane

2. Increases hepatic clearance of LDL-cholesterol from plamsa

- Full effect takes several weeks --> Persistent with chronic administration

- Fully reversible on termination of drug

- Time on the market --> Generic vs. brand and safety data

- Prodrug vs. active drug

- Hepatic uptake mechanism via OATP

- Clearance: P450, renal or biliary

- Elimination half-life

- Potency --> Greatest with newest agents

- Maximum efficacy

- Regression of atherosclerotic plaque

- Plaque stabilization

- Reduction of inflammation and inflammatory markers

- Decreased thrombogenicity

- Reversal of endothelial dysfunction

- Inhibition of leukocyte interaction with antigen-presenting cell

- Contraindicated during pregnancy

- May increase diabetes risk

- Increased levels of serum hepatic enzymes --> Rare but reversible

- Myopathy (myalgia, myositis, or rhabdomyolysis) --> Rare and possibly through mitochondrial toxicity?

- Higher risk with higher dosage of medications

1. Lomitapide: Inhibits microsomal triglyceride transfer protein --> Blocks VLDL assembly and secretion

2. Mipomersen: Inhibits apo B-100 synthesis --> Decreases LDL cholesterol

- Oligonucleotide antisense apo B-100 mRNA protein

- Subcutaneous injection given once a week

- Lesion composed of cells, extracellular matrix, and lipid

- Cells: Endothelial and smooth muscle cells, macrophages, and lymphocytes

- Extracellular matrix: Collagen, elastin, and proteoglycan

- Lipid: Cholesterol esters

- Raised intimal plaque with a core of lipid (necrotic center) and a fibrous cap covering the core

- Most likely locations: Abdominal aorta, coronary, carotid and popliteal arteries

- Response to injury via endothelial dysfunction, lipid insudation, monocyte/macrophage infiltration and smooth muscle cell migration

1. Endothelial cell injury

2. Fatty streak

3. Accumulation of immune cells

4. Smooth muscle cell migration

- Reasons for injury: Hyperlipidemia, hypertension, smoking, hemodynamic factors (turbulence), toxins, viruses, and immune reactions

- Results in cell dysfunction

1. LDL particles migrate into intima --> Become oxidized via the release of reactive oxygen species

- Due to increased angiotensin II release in hypertensives as well as mechanical stress

2. Leukocyte infiltration due to increased endothelial expression of ICAM and VCAM --> Diapedesis

- Accumulation of foam cells within the intima

- Begin to form in infancy --> Universally present by age 10

- Does not disturb blood flow

- Probable precursor to atheromatous plaques

- Foam cells: Macrophages that envelop oxidized LDL particles via scavenger receptors

- Increased production of pro-inflammatory cytokines IL-1, TNF and MCP-1

- Via increased expression of ICAM and VCAM on endothelial cells

- Migrating immune cells take up oxidized-LDL and become foam cells

- Increased pro-inflammatory cytokines (IL-1, TNF, and MCP-1)

- Smooth muscle cells begin to migrate from media to intima

- Migrate from the media into the plaque within the intima

- Begin to deposit collagen and other ECM proteins (elastin and proteoglycans)

- Extracellular lipids accumulates

- Cells respond to increased FGF and TGF-a

- Erosion: Top layers of plaque become exposed to blood and a small thrombus results

- Rupture: More extensive damage --> Larger thrombus forms --> Can be occlusive

- Hemorrhage: Possible in the microvasculature at the corners of atheromas --> Cause larger thrombi

- Thrombosis: Can occur on its own

- Rupture is more common in atheromas that have a large lipid core with a thin fibrous cap

- More clinically significant

- Calcification

- Rupture or erosion

- Internal hemorrhage

- Associated thrombosis

- Medial atrophy/replacement --> Can result in aneurysm or wall rupture

- All of these can lead to progressive arterial stenosis

- Atheromas that are less susceptible to erosion/rupture

- Symptoms develop with exertion

- Significant lesion

- >50% reduction in diameter with 75% reduction in cross sectional area

- Nutritional demand is met at rest, but not with exertion

- Larger than a significant lesion

- Still fixed lesion

- >75% reduction in diameter with 90% reduction in cross sectional area

- Leads to chronic Ischemic Heart Disease

- Nutritional needs are not being met at rest or during exertion

- Plaque with a large lipid core and thin fibrous cap

- Susceptible to erosion, rupture or hemorrhage

- Lumen is usually larger in this case

- Smaller lipid core with thick fibrous cap

- Lumen is usually smaller in this case

- Less susceptible to erosion, rupture and hemorrhage

- Can be caused at the original site of an atheroma

- Atheroma can progress through the media to damage the integrity of the wall

- Vessel wall begins to balloon out

- Very susceptible to rupture!!

- Most likely locations: Abdominal aortic aneurysm or other arteries with lots of branches

- Saccular: Located on one side

- Fusiform: Located on both sides

- False aneurysm/Pseudoaneurysm: Blood escapes through a hole in the media and balloons out on outer vessel surface

- Dissection: Blood forms a new passage through the media layer underneath the adventitia

- Deficiency of blood flow in part of an organ due to stenosis/obstruction of a vessel --> Cannot supply nutrient demand

- IHD syndromes: Angina pectoris, myocardial infarction, sudden cardiac death, and chronic ischemic heart disease

- Insidious onset of heart failure over time due to progressive myocardial damage

- Pathology: Hypertrophy and marked dilation of all 4 chambers

- Histopathology: Myocardial atrophy, myocyte hypertrophy, subendocardial vacuolization and replacement fibrosis

- Results in pulmonary edema, pleural effusion, and hepatic congestion (nutmeg liver)

- 0-4 hours: invisible

- 4-24 hours: Dark mottling

- 1-14 days: Progressively more defined pale area --> Yellow area surrounded by hyperemic zone

- More than 14 days: Gray scarred area

- 1-3 hours: Wavy fiber change

- 4-12 hours: Coagulative necrosis occurs

- 5 hours: Nuclear pyknosis

- 24-48 hours: Karyolysis

- 6-8 hours: Early neutrophilic infiltration

- 48 hours: Peak neutrophilic infiltration

- 4 days: Macrophage infiltration

- 3 days: Vessel proliferation

- 4 days: Fibroblast proliferation

- 9 days: Collagen deposition

- 2-4 weeks: Granulation tissue peak

- >6 weeks: Mature scar

- Location, severity, and rate of occlusion

- Size of vascular bed of occluded vessel

- Duration of survival

- Metabolic demands

- Collateral vessels

- Vasospasm

- Heart rate, rhythm, and BP

- Pericarditis: Hemorrhagic epicardium resulting in fibrinous pericarditis (2-3 days after)

- Cardiac tamponade: Myocardial rupture (3-6 days after)

- Mural thrombi: Can happen anytime

- Papillary muscle infarct/rupture (3-6 days after)

- Myocardial infarct with hemorrhage --> Due to dual blood supply

- Contraction band necrosis: Accelerated necrosis of irreversibly injured myocytes --> After reperfusion (even 2 min after) --> Hypercontraction due to Ca2+ influx

- Ventricular aneurysm and chronic IHD --> Late sequelae

- Cells of sinoatrial node, atrioventricular node, Purkinje fibers, and atrial and ventricular myocytes

- Slightly different action potentials seen for these cell types but essentially the same

- Resting potential is less negative (-60mV)

- Phases 0-4

- Phase 0: Due to Ca2+ current and less rapid upstroke

- Phase 4: Upslope due to specialized Na current

- P-wave: Depolarization of the atria

- QRS Complex: Depolarization of the ventricles --> Don't always have a Q wave and can have weird looking QRS complexes in pathology

- ST segment: Isoelectric segment between the QRS and T wave --> Elevated or depressed with pathology

- T wave: Repolarization of muscle fibers in the ventricle

- Augmented limb leads: aVf (I modified), aVl (II modified, and aVr (III modified)

- Bipolar limb leads: I, II, and III 

- Precordial leads: V1, V2, V3, V4, V5, and V6

- Frontal plane leads are used to determine the QRS axis

- V1 and V2 --> Good view of RV

- V5 and V6 --> Good view of LV

- Read I and aVL together, II, III, and aVf together, V1 and V2 together, V3 and V4 together, and V5 and V6 together

- Determine rate, rhythm, axis, intervals, chamber size, and injury

- Axis: Look at I and aVf leads --> Normal, left, right, and intermediate

- Rhythm: Sinus, atrial, junctional, and ventricular

- Think about normal physiology and the individual patient

- 1 mm= .1 mV and 40 ms

- 5 mm boxes= .2s

- 1 box between --> 300 bpm, 2 boxes --> 150 bpm, 3 boxes --> 100 bpm, 4 boxes --> 75 bpm, and 5 boxes --> 60 bpm

- V1: small R wave and deep S wave

- V2: smaller R wave and deep S wave

- V3+V4: Larger R wave with smaller S wave

- V5+V6: Large R wave

- I+II: Positive R wave

- If negative R wave on I or II --> Not sinus beat or limbs on wrong

- Normal sinus: Every QRS has P wave before --> 60-100 bpm

- Sinus Tachycardia: >100 bpm

- Sinus bradycardia: <60 bpm

- Direction of the ventricular depolarization

- Normal --> Down and to the left --> Between 0 and 90 degrees

- Described by limb leads I and aVf

1. Rightward deflection --> I(-) and aVf(+) --> right heart failure, etc

2. Leftward deflection --> I(+) and aVf (-)

- Physiologic: + II lead

- Pathologic: - II lead

3. Extreme rightward deflection/Intermediate --> I(-) and aVf (-)

- PR interval: .12-.20s --> Some variation is normal based on vagal tone --> Prolonged means slow AV node conduction

- QRS: <.10s --> Wide means bundle branch block, ventricular ectopic beat, toxic drug effect, or severe hyperkalemia

- QT: <.44s after correction for heart rate

- ST segment elevation --> Injury or infarction

- ST segment depression --> Ischemia

- T wave inversion --> Ischemia

- RSR' segment: Seen on V1 --> R' higher than R because RV signal is closer to V1

- Wide QRS complex seen

- RV contraction is delayed because signal must pass from myocyte to myocyte

- V2: Weird notched QRS complex

- V6, I, and aVl Leads: Broader S wave --> R' seen from a different angle

- Delayed LV contraction --> Dysynchronous contraction and always pathologic

- Very weird QRS complexes observed

- V1: small R wave --> Only normal lead

- I, aVl, V5+V6: Broad/deep S wave

- V5+V6: Monophasic or notched R wave

- Very large R waves seen on V5 and V6

1. Cornell Criteria

- S wave on V3 + R wave on aVL= >28mm in men or > 20mm in women

2. Other Criteria

- R on aVL>11 mm or R in I >15mm

- S on V1 + R in V5 or V6 >35mm

- Rightward deviation >+110 degrees

- R/S ratio in V1>1

- S/R ratio in V6>1

- R wave in V1 >7mm

- S wave in V1 <2mm

- qR pattern seen in V1

- rSR' in V1 with R'>10mm

1. Left atrial enlargement

- P terminal force in V1 is more negative than 0.04mm/sec

- Leftward shift of P-wave axis

- Notched P wave in II or III

2. Right atrial enlargement

- P wave is tall and peaked with a height >2.5mm in II, III, or aVf

- Rightward shift of P-wave axis

- Positive deflection of the P-wave in V1 or V2 is greater than 1.5 mm

- Premature atrial contraction: Occurs before the next sinus beat is expected --> Looks different

- Premature ventricular contraction: Strange looking QRS complex (wider and distorted) --> Not preceded by P wave

- Normal: <120/<80

- Prehypertension: 139-120/89-80

- Stage I Hypertension: 159-140/99-90

- Stage II Hypertension: >160/>100

- For hypertension values --> Can qualify with either systolic or diastolic values

- ~75 million people over 20 years old with hypertension

- 50% of people over the age of 60

- Only 79% are aware they have hypertension

- 69% are on drug treatment to lower their BP

- Only 45.4% of patients treated are controlled to <140/<90

- Complications: End organ failure leading to brain hemorrhage/stroke, retinopathy, peripheral vascular disease, LVH/CHF, and renal failure

- Mortality doubles with every 20 mmHg increase in blood pressure

- Mean Arterial Pressure (MAP) --> Depends on CO and TPR

- CO= SV x HR

- TPR depends on vascular structure and tone and blood volume

- Accounts for 90-95% of cases --> Unknown etiology

- Contributing Factors: Increased sympathetic activity, increased AII activity and mineralocorticoid excess, genetic factors, increased sodium intake, obesity and weight gain

- Only 5% of cases --> Known etiology

- Sleep apnea

- Drug-induced

- Chronic kidney disease

- Primary aldosteronism

- Renovascular disease

- Chronic steroid therapy and Cushing's syndrome

- Pheochromocytoma

- Coarctation of the aorta

- Thyroid or parathyroid disease

- Lose weight if overweight (BMI <25 kgm2)

- Adopt Dietary Approaches to Stop Hypertension eating plan (DASH) --> Emphasizes fruits, vegatables, low fat dairy, reduced sodium intake, whole grains, poultry, fish, and nuts

- Reduce sodium intake to no more than 100 mmol/day (2.5 g)

- Increase aerobic activity --> 30-45 min most days of the week

- Limit alcohol consumption

- Stop smoking

- Reduce saturated fat intake

- Maintain adequate intake of K, Ca, and Mg

- Weight reduction --> 5-10mmHg/10kg

- DASH eating plan --> 8-14 mmHg

- Dietary sodium reduction --> 2-8 mmHg

- Physical activity --> 4-9 mmHg

- Limit alcohol consumption --> 2-4 mmHg

- Diuretics

- Agents affecting adrenergic function

- Vasodilators

- Agents affecting the Renin Angiotensin Aldosterone System (RAAS)

- Results of treatment: 2 mmHg reduction leads to 7% reduction in CVD mortality and 10% reduction in stroke mortality

- Inhibits salt and water reabsorption

- Decreases blood volume

- Therefore decreases TPR and BP

- Thiazide diuretics are first line for treatment

- Low dose thiazides --> Systolic hypertension only

- Loop diuretics --> Removal of edema

- Elevated plasma renin, angiotensin II, and aldosterone --> Reflexive BP increase

- Levels increase due to volume and sodium depletion

1. B-Blockers (Metoprolol): Block B1 receptors

- Decreased HR, CO, and CF

- Decreased renin release --> Decreased AII and TPR

2. CNS A2 agonists (clonidine): Stimulate A2 receptors

- Not used routinely for hypertension treatment in the elderly --> CNS effects and orthostatic hypotension

3. Selective A1 antagonists (prazosin): Block vascular A1

- Vasodilation, decreased TPR and MAP

- Do not use in CHF!! --> Tachycardia due to reflex responses

- Amlodopine, diltiazem, and verapamil

- Arterial smooth muscle --> Block L-type voltage gated Ca channels --> Prevent Ca influx --> Vasodilation

- Cardiac Tissue: "non-dihydropyridine" compounds block Ca entry into myocytes

- Adverse effects: Reflex tachycardia and ankle edema

- Drug interaction: May precipitate AV block with other drugs (B-blockers)

- Angiotensin Converting Enzyme (ACE) Inhibitors

- Angiotensin AT1 receptor blockers (ARB)

- Side Effects: Hyperkalemia when ACEI/ARB used with K-sparing diuretic

- Diabetes --> All antihypertensives

- Chronic kidney disease --> ACEI and ARB

- Heart failure --> Thiazides, B-blockers, ACEI, ARB, and Aldo antagonists (spironolactone)

- Post-myocardial infarction --> B-blocker and ACEI

- High CAD risk --> All antihypertensives

- Experimental surgical procedure --> Ablates the sympathetic innervation of the kidney

- Used in patients with drug resistant hypertension

- Severe hypertension only!!

- Renin secreted by the juxtaglomerular cells in the kidney

- Renin cleaves angiotensinogen to angiotensin I

- Angiotensin converting enzyme (ACE) cleaves AI to AII

- AII stimulates aldosterone release from the adrenal gland

- AII --> Vasoconstriction, macrophage activation, endothelial cell dysfunction, increased lipoxygenase activity, heart hypertrophy, and platelet aggregation

- Drugs with -pril

- Inhibits ACE to inhibit the conversion of AI to AII

- Inhibits the resulting vasoconstriction, endothelial dysfunction, increased lipoxygenase activity, hypertrophy, macrophage activation and platelet aggregation that results

- Differences in specific drugs: Potency, elimination, duration of action, tissue specificity, SH-group, and prodrug vs. active drug

- Altered peripheral resistance (TPR) --> Rapid pressor response

- Altered renal function (Na reabsorption and aldosterone release) --> Slow pressor response

- Altered cardiovascular structure --> LV hypertrophy and remodeling

- Brain --> Stroke due to atherosclerosis and vasoconstriction

- Vasculature --> Vasoconstriction, vascular hypertrophy, and endothelial dysfunction

- Heart --> LV hypertrophy, fibrosis, remodeling and apoptosis

- Kidney --> Decreased GFR, proteinuria, increased aldosterone release and glomerular sclerosis

- Cardiac myocyte --> Hypertrophy and NE release

- Fibroblast --> Hyperplasia, collagen synthesis, and fibrosis

- Peripheral artery --> Vasoconstriction, endothelial cell dysfunction, hypertrophy, and decreased compliance

- Kidney --> K loss and sodium retention

- Leads to ischemic events, progressive heart failure and sudden cardiac death!! 

- Hypotension in hypovolemic patients

- Renal insufficiency in patients with volume depletion, hypotension and bilateral renal stenosis

- Hyperkalemia in patients on K-sparing diuretic, COX inhibitors, diabetics with hyporeninemic hypoaldosteronism and Na restricted patients

- Cough and angioedema --> Kinin related (Increased bradykinin levels)

- Neutropenia, nephrotic syndrome, skin rash, and taste disturbances --> Captopril especially!!

- Intolerance --> History of angioedema or anaphylaxis

- Bilateral renal stenosis

- Pregnancy

- Renal insufficiency

- Hyperkalemia

- Severe hypotension

- Via chymase in the liver

- Angiotensinogen in the liver converted to AII

- Escapes ACE inhibition

- Drugs with -sartan

- Block AT1 receptor specifically

- AT1 receptor leads to vasoconstriction and proliferation

- AT2 receptor leads to vasodilation and anti-proliferative effect

- Thought to have more complete renin system inhibition

- Comparable to ACE inhibitors in almost all situations

- Fewer side effects --> Cough and angioedema --> No bradykinin effects

- Same renal effects

- Direct renin inhibition preventing angiotensinogen conversion to angiotensin I

- Similar effects as ACE inhibitors

- Side effect: Diarrhea at high doses --> Others largely unknown!! 

- Dose adjustment for fecal elimination but no dose adjustment for renal insufficiency

- Can cause LV mass regression

- Not really used clinically because side effects are so uncertain!!

- Hypertension --> Prevention or reversing LVH

- Secondary prevention of vascular disease

- Post-acute MI

- Improving survival and hemodynamics in CHF

- Protecting against progression of neuropathy (diabetic and non-diabetic)

- Reduction of AII levels --> Reduce vasoconstriction

- Sympatholytic effects --> Central and peripheral

- Increase vasodilatory effects of bradykinin and prostaglandins

- Reduce LVH

- Improves symptoms

- Reduced remodeling and progression

- Reduce hospitalization of patients

- Improved survival

- Reduces the progression of renal disease

- Improves intraglomerular pressure via dilation of the glomerular arterioles

- Helps increase GFR and RPF

- Finely dynamic process of maintaining fluidity of blood, repairing vascular injury, and limiting blood loss

1. Local vasoconstriction

2. Formation of primary plug

3. Formation of thrombus (secondary plug)

4. Fibrinolysis

- Formation of primary platelet plug

- Initiated by vascular injury --> Blood exposed to underlying ECM

- Platelet adhesion and activation via thromboxane A2 and IIb/IIIa integrins --> Results in fibrinogen binding

- Platelet granule release via ADP, TXA2 and Ca release

- Formation of secondary plug (coagulation)

- Sequential proteolytic cascade leading to the cleavage of fibrinogen to fibrin

- Many steps require Vitamin K as a co-factor

1. Endothelial cells secrete t-PA

2. Thrombomodulin --> Binds Factors V and VIII

3. Prostacyclin

4. Antithrombin III --> Inactivates Factors IIa, IXa, Xa, XIa, and XIIa

5. Tissue Factor Pathway Inhibitor --> Inhibits extrinsic pathway

- Inappropriate clot formation --> >2 million deaths/year

- Emboli: Dislodged thrombus that travels

- Can lead to ischemia or infarction

- Results from arterial or venous thrombi

- Risk factors: Endothelial cell injury, recent surgical procedures, hypercoagulability, and oral contraceptives

- Oral contraceptives --> Increased hepatic synthesis of clotting factors

- Antiplatelet Drugs --> Acetylsalicylic acid (aspirin), P2Y12 antagonists, and GPIIb/IIIa antagonists

- Low dose aspirin --> 325 mg/day

- Selectively inhibits thromboxane A2 synthesis via COX-1

- Absorption: Rapid oral absorption --> Peak conc. 15-20 min after dose

- Higher dose --> Inhibition of prostacyclin production and reduction in clinical efficacy for antiplatelet effect

- No antiplatelet drug is more effective than aspirin

- Side effects: Increased incidence of hemorrhagic stroke and GI bleeding

- Plavix

- Inhibits P2Y12ADP receptor --> Inhibits ADP receptor for glycoprotein IIb/IIIa pathway

- Pathway is crucial for cross-linking platelets

- Prodrug --> Metabolized by CYP2C19 in the liver

- Side effects: Prolonged bleeding, thrombotic thrombocytopenia purpura, and FDA black box warning for CYP2C19 mutants

- Therapeutic Uses: Reduction of stroke, MI, unstable angina, and death in patients with recent MI or stroke

- CYP2C19 polymorphisms (3) --> Normal function (1) and loss-of-function alleles (2)

- FDA black box warning --> Warn about reduced effectiveness in patients who are poor metabolizers

- Inform health care professionals that tests are available

- Advise healthcare professionals to consider use of other anti-platelet medications

- GPIIb/IIIa Platelet Receptor inhibitors --> Monoclonal antibody

- Therapeutic Uses: Reduces restenosis and recurrent MI when used with aspirin and heparin

- Side effects: Major hemorrhagic event in 1-10% of patients

- Act on the clotting cascade

- Heparin

- Warfarin

- Dabigatran

- Catalyzes the inhibition of factors IXa, Xa, and thrombin by enhancing antithrombin III activity

- Increases antithrombin III activity 1000 fold

- Testing is required to determine dose effect on coagulation

- Absorption: No PO absorption, IV or SC only

- Must be monitored!! 

- NOT for long term therapy

- Measuring the activated partial thromboplastin time (aPTT)

- Normal: 25-39s, therapeutic range: 2-2.5x normal

- Monitored every 6 hours when given IV

- Not monitored when given SC

- Use: Venous thrombosis, pulmonary embolism, angina, acute MI, atrial fibrillation, vascular surgery, and catheter implantation

- Safe to use during pregnancy!! --> Doesn't cross placenta

- Side Effects:Hemorrhage, osteoporosis, spontaneous fractures, and heparin-induced thrombocytopenia (1-4%)

- Contraindications: Hemorrhage, thrombocytopenia, hypertension, renal or hepatic disease, endocarditis or history of HIT

- Protamine can be given to antagonize overdose effects

- Occurs 5-14 days after therapy

- 50% decrease in platelets

- Highest risk in post-operative patients and women

- Immune system develops IgG antibodies to heparin --> Forms complex

- Systemic hypercoagulation results

- Can cause DVT, PE, MI, stroke, necrosis, organ infarction and death

- Treatment: Give alternative anticoagulant, stop heparin, and administer hirudin to irreversibly inhibit thrombin

- Enoxaprin and fondaparinux

- Inhibits Factor Xa by antithrombin

- Use: Venous thromboembolism, thrombosis, pulmonary embolism, and unstable angina

- Monitor with renal insufficiency, obesity and pregnancy

- Incomplete neutralization by protamine

- Advantages over heparin: Longer half life, faster absorption, once daily SC injections, lower risk of thrombocytopenia and osteoporosis

- Most widely used anticoagulant due to predicatabilty of the pharmacokinetics

- Blocks carboxylation of glutamate in prothrombin and Factors VII, IX, and X --> Inactive coagulation factors

- Vitamin K epoxide reductase converts factors to active

- Slow onset of action (8-12 hours) --> Maximal effect 3-5 days after administration

- Must be closely monitored!!

- Initiate at 5-10 mg

- Maintenance dose of 5-7mg/d

- Monitor using international normalized ratio (INR)

- INR=PTpt/PTnormal

- Normal INR=1

- Therapeutic INR= 2-3

- Pt with tilting disk heart valves=2.5-3.5

- Use: Acute DVT, pulmonary embolism, venous thromboembolism, acute MI, prosthetic heart valve replacement, and chronic atrial fibrillation

- Side Effects: Hemorrhage which increases with intensity and duration of therapy and teratogenic effect in pregnant women

- Drug interactions: Increases metabolism with aspirin, anabolic steroids, antibiotics, etc, and decreases metabolism with chronic alcohol abuse, oral contraceptives, corticosteroids, barbiturates, etc.

- Direct thrombin inhibitor

- Oral dosing twice daily

- Low MW pro-drug, rapidly converted to active form

- Use: Stroke prevention in patients with atrial fibrillation (only US approved use)

- Side Effects: Hemorrhage, heartburn, stomach upset, and increased risk of MI

- Contraindiciations: Not yet established

- Benefits: No monitoring needed, rapid onset of action, no adverse drug reactions

- Issues: Cost!!!!!

- Streptokinase, Alteplase, Reteplase, and Tenecteplase

- Effective only if used rapidly after onset of thrombosis

- Use: Acute ischemic stroke and MI, pulmonary embolism, severe deep venous thrombosis, and ascending thrombophlebitis

- Inhibitors: Aminocaproic acid --> Inhibits plasminogen to plasmin conversion

- Side effect: Hemorrhage --> Intracranial most severe

- Contraindications: Brain tumor, aneurysm, stroke, major surgery within 14 days, active bleeding in GI or urinary tract, severe platelet shortage and severe uncontrolled hypertension

- First thrombolytic available

- Catalyzes the conversion of plasminogen to plasmin

- Acts throughout the circulation --> Systemic effect

- Side effects: Allergic reaction, tolerance, and increased bleeding risk

- Alteplase, reteplase, and tenecteplase

- Endogenous thrombolytic agent --> Human gene cloned, expressed and purified from bacteria

- Preferentially activates plasminogen bound to fibrin --> Within an active clot

- t-PA is effective at lysing thrombi during treatment of acute MI

- Fat-soluble vitamin found in leafy green vegetables

- Vitamin K is synthesized by intestinal flora

- Causes: Hospitalized patients due to poor diet, parenteral nutrition, surgery or multiple antibiotic therapy

- Symptoms: Bleeding and osteoporosis

- Treatment: Oral or parenteral Vitamin K1 --> Onset of effect is delayed for 6 hours

- Rapid administration IV can produce dyspnea, chest and back pain, and even death!!

- Spontaneous bleeding occurs when coagulation factor activity is less than 5-10% of normal

- Hemophilia A/Classic Hemophilia --> Factor VIII deficiency --> Treated with lyophilized factor VIII

- Hemophilia B/Christmas Disease --> Factor IX deficiency

- Fibrinogen deficiency --> Cryoprecipitate can be obtained from whole blood and can isolate fibrinogen from that

1. Left Main Coronary Artery --> Between LA and pulmonary trunk to reach AV groove --> Left Anterior Descending and Left Circumflex Branches

- LAD --> Anterior 2/3 of septum and apical portion of the anterior papillary muscle

- Left circumflex --> Posterior and lateral surface of the LV

2. Right Coronary Artery --> Right AV groove --> Posteriorly between RA and RV 

- Right Coronary Artery --> RV via acute marginal branches

- Posterior descending artery --> Inferior and posterior aspect of the ventricles and posterior 1/3 of septum

- AV node artery --> Supplies the AV node

- Right dominant system --> Normal

- Left dominant system --> Posterior descending and lateral branches off left circumflex instead --> More prone to problems with atherosclerosis

- Co-dominant --> Posterior inferior ventricles supplied by both the left and right main branches

- Atherosclerosis of coronary arteries

- Thickness of the wall that artery supplies

- Dual blood supply/collaterals

- Coronary vasospasm

- Hypoxemia due to anemia or hypotension

- Coronary vasculitis

- Coronary anomalies --> 2nd leading cause of death in young athletes and military recruits

- Myocardial contractility --> Assessed by BP and HR

- Wall stress

- Chest discomfort --> Determine quality, location, severity, provocative factors, and relief

- Age, gender, and risk factors

- Classes of angina --> I:much exertion, II:moderate exertion, III:minimal exertion, and IV:at rest

- Use history to determine true cardiac from GI, musculoskeletal and pulmonary pain!!

- Hypertension

- Weight and body habitus

- Vascular bruits

- Heart size --> PMI

- Skin condition

- Eye grounds --> Xanthelasma or corneal arcus --> Cholesterol deposits

- Normal EKGs are taken in the office and used essentially as part of the physical exam --> Look for ST depression or elevation

- Helps diagnose atypical presentation of CAD --> Not necessary really in typical presentations

- Slowly increase the amount of exertion for the patient

- Slowly increases HR, BP, and wall stress and observe ECG results

- Must determine exercise capacity --> 1 MET= 3.5 mLO2/kg/min or 1 kcal/kg/hour

- Increased MET value --> Increased prognosis

- Must achieve 85% of max HR during test for it to be accurate

- Max HR= 220-age

- Sensitivity --> 70%

- Specificity --> 70%

- PPV --> 63/66 --> 95%

- NPV --> 7/34 --> 21%

- Values vary depending on whether the population has high or low prevalence of diease --> These represent high prevalence

- Diagnosis of CAD

- Adequacy of medical or revascularization treatment

- Activity counseling

- Exercise prescription

- Rhythm assessement

- Diagnosis of valvular heart disease --> Aortic stenosis, mitral stenosis, mitral regurgitation, and hypertrophic obstructive cardiomyopathy

- Performed in patients with abnormal resting ECGs

- Provide increased diagnostic accuracy --> Sensitivity 85-90% and specificity 85-90%

- Helps localize ischemia to the specific vessel or territory

- Echo taken before and after exercise and differences are examined

- Contrast can also be added for contrast echo

- Tomographic imaging planes

- Inject radioisotope into patient and examine where the isotope goes

- Takes cross sections on multiple planes 

- Compare rest and stress scans to determine ischemia

1. Injection of dobutamine --> Beta agonist --> Increased HR, BP, and contractility

- Echo taken before and after injection

2. Nuclear perfusion scan can also be taken before and after administration

- Injection of adenosine or dipyridimole --> Direct coronary vasodilator with minimal change in HR, BP, and contractility

1. Positron Emission Tomography (PET) --> Higher energy, higher resolution, shorter time, but expensive!!

2. Single Photon Emission Computed Tomography (SPECT)

- Lower energy, lower resolution, and takes alot longer

- Less expensive

- Current gold standard for true diagnosis of stenosis

- Quantitative

- Clearly defines anatomy

- Useful in revascularization planning

- Not a functional test

- Invasive procedure --> Risky!!

- Inject contrast into vessels and use CT technology to view coronary vasculature

- Scanning time --> 5-7 secs

- High radiation dose --> 50x CXR

- High negative predictive value vs. cardiac catheterization to exclude CAD

- Chest pain or discomfort due to myocardial ischemia or reduced blood flow

- Stable angina --> Remains stable and doesn't progress --> Becomes unstable if it progresses suddenly

- Unstable angina --> New presentation or gets progressively worse suddenly

- Responsible for angina, unstable angina, SOB for acute LV dysfunction, and arrhythmias

- Oxygen supply and demand mismatch --> Pathophysiology

- Due to:

1. Atherosclerotic narrowing of coronary artery

2. Reduced oxygen supply via anemia or hypotension

3. Increased oxygen demand due to tachyarrhythmias, hypertensive emergencies, or severe aortic valve stenosis

- Hyperthermia

- Hyperthyroidism

- Drugs such as cocaine or meth

- Hypertension

- Anxiety

- Hypertrophic cardiomyopathy

- Anemia

- Hypoxemia

- Sickle Cell Disease

- Drug toxicity such as cocaine or meth

- Pneumonia

- Obstructive Sleep Apnea

- Occurs in an unstable plaque --> Thrombosis formation due to erosion or rupture of plaque

- NSTEMI: Non-ST segment elevation myocardial infarction

- STEMI: ST-elevation myocardial infarction

- Discomfort in the chest, jaw, shoulder, back or arm

- Aggravated by exertion or emotional stress

- Relieved by nitroglycerin

- Increased occurance in patients with CAD

- Can also occur in patients with valvular disease, hypertrophic cardiomyopathy, and uncontrolled hypertension

- Can occur in patients with vasospasm and without plaque formation

- Increased wall stiffness

- Decreased myocardial contractility

- Repolarization abnormalities --> ST segment changes

- Arrhythmias/sudden death

- Symptoms of angina

- LV systolic function --> Necrosis of heart tissue

- Beta blockers

- Calcium channel blockers

- Nitrates

- Morphine

- First line treatment for exertion angina --> Mortality reduction in pts with history of MI or systolic heart failure

- Competitively inhibit B receptors --> B1 in heart and B2 in vascular smooth muscle

- Metoprolol is highly selective for B1

- Labetalol and carvedilol --> Also block alpha receptors

- Some lipid soluble --> Hepatically cleared and can cross the BBB --> CNS side effects (metoprolol and propranolol)

- Low dose pindolol for a patient with a low resting HR

- Reduce myocardial oxygen demand and decrease renin release from the kidney

- Bronchospasm

- Bradycardia

- Depression, nightmares and insomnia

- Fatigue

- Erectile dysfunction

- Dihydropyridine --> Amlodipine --> More effect on vasculature

- Non-dihydropyridine --> Verapamil and diltiazem --> More effect on heart

- Block L-type voltage gated Ca channel in heart and vasculature

- Dilate coronary arteries and peripheral arterioles

- Decreases cardiac contractility and AV node conduction

- Also vasodilates coronary arteries and peripheral vasculature

- Edema --> Amlodipine

- Constipation

- Nausea

- Headache

- Rash

- Hypotension

- Dizziness

- Liver dysfunction

- Gingival hyperplasia

- Sexual dysfunction

- Avoid in patients with heart failure --> May worsen symptoms!!

- Short acting --> Nitroglycerin --> Sublingual (.3-.4 mg dose)

- Intermediate acting --> Isosorbide dinitrate (twice daily) --> 10-20 mg

- Long acting --> Isosorbide mononitrate (once daily) --> 30-120 mg

- Venodilators, coronary vasodilators, and arteriolar dilators --> Metabolized in cells to liberate NO

- Decrease myocardial oxygen demand --> Systemic vasodilation

- Improve exercise tolerance in chronic stable angina

- Venodilation --> Lowers preload --> Decreases wall stress and decreases oxygen demand

- Dilate coronary arteries --> Especially helpful in patients with vasospasm

- Anti-platelet and anti-inflammatory effects --> Inhibits IIb/IIIa binding

- Lipophilic compounds --> Rapidly absorbed from the skin and GI tract

- IV preparations also available

- Effects are exacerbated by sildenafil --> Cannot take within 24 hours of taking viagra

- Attenuation of the vascular effects

- Not due to altered pharmacokinetics

- Can be reduced by using intermittent therapies

- Headache and flushing

- Hypotension

- Contraindications --> Sildenafil within 24 hours, hypertrophic cardiomyopathy, acute RV infarction, and severe aortic stenosis

- Patients with severe aortic stenosis are very preload sensitive!!

- Increased preload with the same afterload --> Increased SV

- Increased contractility means the heart can handle a higher preload --> Increased SV

- Increased afterload without increased contractility --> Decreased SV with the same preload --> Increased ESV

- Technical Definition: When heart is unable to pump the blood at the rate required or the heart can only do so with an increased filling pressure

- Operational Definition: Clinical syndrome resulting from cardiac decompensation characterized by interstitial volume overload and/or inadequate tissue perfusion

- Myocardial infarction --> Atherosclerosis 

- Toxins --> Alcohol, etc

- Chronic hypertension --> Increased afterload

- Myocarditis --> Any infection

- Idiopathic/genetic causes

- Cardiomyopathy

- Systolic HF: Post-MI/myocarditis --> Thin walls with dilated ventricle size --> Doesn't contract well so decreased contractility and SV

- Diastolic HF: Hypertension and hypertrophy --> Very thick walls but contracts well --> Problem with filling due to ventricle size --> Decreased SV but normal contractility

1. Volume expansion

- Renal mechanisms --> RAAS and vasopressin highly activated in HF patients

- Venous constriction

- Increased preload --> Increased CO but with elevated filling pressure

2. Neurohumoral Activation

- RAAS and sympathetic nervous system activation --> Highly activated in HF patients

- Increased contracility and HR --> Increased CO

- Vasoconstriction --> Venoconstriction but increased afterload and blood flow redistribution

- Results in volume expansion as well

- All lead to myocardial remodeling due to mechanical stress, AII, NE/E, inflammatory cytokines, oxidative stress, and endothelin production

- Compensatory hypertrophy --> Occurs within days to months in athletes --> Completely reversible when stress removed

1. Abnormal calcium handling --> Ca resequestration highly decreased --> Increased Ca during systole and diastole --> Poor relaxation

2. Apoptosis of myocytes --> Stimulated by mechanical stress, B-agonists, inflammatory cytokines, AII, reactive oxygen species, etc

3. Abnormal amounts of interstitial collagen --> LV cavity dilation and/or impaired relaxation of LV

- Hypertrophy

- Myocardial dysfunction

- Myocyte apoptosis

- Myocardial remodeling

- All lead to the development of heart failure --> Either systolic or diastolic

- Decreased amplitude of contraction due to impaired calcium release

- Loss of functional myocytes by necrosis or apoptosis

- Altered sarcomere function --> Changes in protein content, isoforms and/or function

- Left ventricular remodeling --> Increased chamber size and wall thinning

- Impaired relaxation due to impaired Ca reuptake into SR

- Increased LV wall stiffness due to increased fibrosis and/or alteration in sarcomere properties

- Left ventricle remodeling with increased wall thickness

- Normal or small LV chamber size

- 5 million people affected --> 400,000 new cases/year and 260,000 deaths/year

- Annual mortality of 30-50% with severe and 10-20% with mild/moderate HF

- Increasing incidence in the US because people are living longer

- Women, elderly, diabetics and hypertensives are more predisposed to develop diastolic HF (HFpEF)

- Patients with coronary artery disease are predisposed to develop systolic HF (HFrEF)

- Fatigue, cold extremities, mental obtundation, and kidney or liver dysfunction --> Increased CO

- Tissue congestion --> SOB and leg or abdomen edema

- Left sided congestion --> SOB

- Right Sided congestion --> Leg and abdomen edema

- Classification: I (No limitation), II (Mild limitation), III (marked limitation), and IV (severe limitation)

- Prognostic Predictors: classification, co-morbidity, ejection fraction, functional capacity, plasma neurohormones, and ventricular arrhythmias

- Laboratory Evaluation: Electrolytes, BUN, Cre, LFTs, INR, CK, TnI, TFTs, and consider Fe studies, HIV, and ESR values

- Also evaluate EKG, chest x-ray, and echocardiogram

- Eliminate symptoms

- Stabilize hemodynamics

- Correct organ hypoperfusion

- Prepare for transition to chronic therapy

- Parenteral diuretics --> Furosemide

- Parenteral vasodilators --> Nitroprusside, nitroglycerine, and nesiritide

- Parenteral ionotropes --> Dobutamine and milrinone

- Reduce venous congestion --> Improve SOB and edema

- Reduce end-diastolic volume and wall stress --> Anti-remodeling

- Drawbacks --> Electrolyte problems, RAAS activation, and overdiuresis problems

- Same results in chronic HF treatment as well

- Dose needs to be titrated for specific patient

- Reduce the vasoconstrictive effects of RAAS and sympathetic activation

- Reduces CO and left ventricular filling pressure

- Hydralazine --> Arteriodilator --> Decreased afterload --> Can cause pedal edema

- Nitrates --> Venodilator --> Decrease preload

- Nitroprusside: NO donor --> Decreases both preload and afterload --> Contains CN so toxicity possible and needs titration

- Natriuretic Peptides (Nesiritide): Increased ANP & BNP in serum --> Unique receptor for vasodilation --> Decreases preload and afterload but much safer than Nitroprusside

- Ionotropes (Dobutamine, isoproterenol, dopamine, and milrinone)

- Dobutamine --> Selective B1 agonist --> Increased HR and contractility by increased Ca concentration --> Must be titrated and risk of desensitization

- Isoproterenol --> B1+B2 agonist --> Increased heart contractility and vasodilator of vasculature

- Dopamine --> D-agonist --> Selective for renal vasculature in low doses --> High doses non-specific for A and B-receptors

- PDE Inhibitors (Milrinone): Inhibits cAMP degradation --> Increased heart contractility and potent vasodilation --> No issue with desensitization

- Tachycardia

- Arrhythmias

- Ischemia

- Hypotension --> Only in PDE inhibitors due to potent vasodilatory effect

- Increased systemic resistance --> Need vasodilator as well as diuretics, etc

- Low systemic resistance --> Ionotrope like dobutamine and maybe even dopamine to vasoconstrict and raise resistance

- Reduce or eliminate symptoms

- Increase quality of life

- Prolong survival --> Decrease mortality

1. Oral diuretics --> Reduce volume

2. Oral ACE inhibition --> Reduce symptoms by inhibiting RAAS, vasodilating and reducing aldosterone levels

3. Aldosterone inhibition (spironolactone) --> Directly reduces aldosterone levels --> Increased survival with ACE inhibitor

4. Oral Vasodilators (Hydralazine/Isosorbide dinitrate combination) --> Increased survival in African Americans

- A1 blocker (prazosin) --> No improvement in survival

- Many don't work! --> Ca channel blocker, prostacyclin, etc!!

5. B-blockers (Metoprolol and carvedilol) --> Increased LVEF in 3 months --> Takes time to develop effect and modifies remodeling

6. Ionotropes (Digoxin/Digitalis) --> Inhibits Na/K ATPase --> Increases Ca --> Increased vagal tone and decreased sympathetic tone --> Decreased vasoconstriction, and HR (decreased AV conduction)

- Decreased hospitalization with digoxin therapy

- Increased survival with ACE inhibitor and B-blocker treatment

- Almost always on a diuretic

- ACE inhibitors/ARBs --> Unless contraindicated

- Spironolactone --> Class III-IV HF patients

- Hydralazine/isosorbide dinitrate --> African Americans

- Digitalis --> Class III and IV HF patients --> Symptoms relief and hospitalization reduction --> Only for HFrEF patients

- HFpEF

- No real drug regimen guidelines --> Studies done on systolic HF (HFrEF) patients

- Control BP --> <130/<80 mmHg

- Control ventricular rate and prevent arrhythmias

- Reduction in central blood volume with diuretics

- SA node --> Right atrial --> Left atria --> AV node --> Septal depolarization --> Ventricular QRS complex --> Ventricular repolarization (T-wave)

- PR segment --> Isoelectric --> Conduction time from SA node to AV node and septum

- ST segment --> Isoelectric before repolarization

- U wave: Late repolarization of His/Purkinje system --> Only present sometimes

- V1+V2: Sit over the RV --> small initial + (septal depolarization) followed by - QRS complex

- V3+V4: Sit over septum --> R wave gets progressively taller while S wave gets smaller --> No Q wave

- V5+V6: Sit over LV --> Tiny - but mostly + QRS --> Has Q wave

- I: Between right and left arm --> + if electrical current from right to left

- II: Between right arm and foot --> Always +

- III: Between left arm and foot --> Free (- or +) depending on patient

- Normally upright in leads I, II, aVf, V4-V6

- Negative in aVr

- Often biphasic (pos-neg) in V1

- Duration: <0.12 s (3 small boxes)

- Amplitude: <0.25 mV (2.5 small boxes)

- LA hypertrophy --> Broad and notched P wave

- RA hypertrophy --> Tall and narrow peaked P wave (P pulmonale)

- Ectopic atrial focus --> Inverted or biphasic (neg-pos) in leads I, II, aVf, and V4-V6

- Retrograde P waves: Negative P wave following QRS

- Every P wave should be associated with a QRS

- PR should be stable --> 0.14-0.20s

- PR interval changes with HR so must be modified

- Variability of PR interval --> AV conduction abnormality

- PR interval >0.20s

- Long RR interval due to non-conductive P wave

- Mobitz Type I/ Wenckebach: Progressive prolongation of PR interval before a non-conductive P wave --> AV node abnormality

- Mobitz Type II: Stable PR interval before and after pause --> Pause may last for 2 or more beats --> His/Purkinje system abnormality

- 2:1 AV block: Every other beat has non-conducting P wave --> Either Mobitz type I or type II

- Complete heart block

- No relationship between P waves and QRS complexes

- Totally different atrial and ventricular rates --> Atrial is faster than ventricular rate

- QRS complexes due to escape rhythm --> Either junctional or ventricular

- Etiology of QRS complex depends on the morphology NOT rate

- Normal looking QRS complex in leads I, II, aVf, and V4-V6

- Negative QRS in aVr

- R wave amplitude progressively increases and S wave depth decreases from V1-V6

- R/S becomes >1 in leads V3-V4 (Transition Point)

- Increased QRS amplitude in precordial and/or limb leads in young patients and with myocardial hypertrophy

- Low voltage QRS: <5mm in limb leads or <10 mm in precordial leads --> Due to loss of muscle mass, effusion, thick pericardium, lung disease and obesity

- Small septal Q waves normally seen in limb leads and lateral precordial leads (V5+V6)

- Significant Q waves: >0.04 sec and/or >1mm in depth --> Old myocardial infarction

- Inferior Wall MI: Q waves and ST abnormalities in leads II, III, and aVf --> Supplied by RCA

- Anteroseptal MI: Q waves and ST abnormalities in V1-V2 --> Supplied by LAD 

- Anteroapical MI: Q waves and ST abnormalities in V3-V4 --> Supplied by LAD

- Anterolateral MI: Q waves and ST abnormalities in V5-V6 --> Supplied by LAD

- Lateral MI: Q waves and ST abnormalities in I and aVL --> Supplied by Left circumflex artery

- Posterior MI: Tall R wave in V1 (R/S>1) with duration >0.04s --> In association with inferior MI --> RCA

- Normal: 0.06-0.10s --> Does not change with HR

- Intraventricular conduction delay (IVCD): >0.1s duration

- Left or Right Bundle Branch Block: >0.12s --> RSR' for RBBB and wide QRS with LBBB

- Hyperkalemia: >0.24s duration --> Medical emergency --> Can cause death! 

- Electrical/QRS alternans --> Beat to beat changes in QRS amplitude due to changes in T wave amplitude/morphology

- Begins at J point and ends at the onset of T wave

- Slightly concave and smooth --> Isoelectric

- ST elevation: Early repolarization (LVH or normal), transmural ischemia, MI, aneurysm, and pericarditis

- Pericarditis --> Diffuse ST segment elevation in all leads

- ST depression: Subendocardial ischemia --> Upsloping, horizontal or downsloping

- Onset of QRS complex to the end of the T wave

- Must be corrected for HR (QTc) --> 0.44-0.48s

- QRS complex duration is part of the calculation and correction process

1. Long QT interval causes:

- Delayed repolarization (low Ca or Mg) --> Long ST with normal T

- Prolonged repolarization (drugs or congenitally) --> Normal ST with broad T wave

2. Short QT interval: High Ca or Mg or congenital short QT syndrome

- Normal: Asymmetric with slower upstroke and faster downstroke --> Both smooth

- Notched or irregularities --> May be superimposed P waves

- T waves are tall, peaked, and symmetric: Hyperkalemia

- T wave abnormalities are common: Flat, biphasic, or inverted --> LVH, pericarditis, ischemia, myocarditis, metabolic abnormalities, CNS abnormalities or non-specific

- Ischemic myocardial event that is a direct consequence of atherosclerotic plaque activation and local thrombus formation --> Unstable plaque formation

- ACS is the #1 killer of women in the US

- .33 million/year for STEMI

- 1.24 million/year for UA/NSTEMI

- 1/3 of patients with these events will die --> Most occur before patients receive medical attention

- Hospitalized mortality is 5-10%

- Fissure size and extent of exposure to subendothelial tissues 

- Tissue factor expression on endothelial cells

- Plasminogen activator inhibitor type I levels

- Levels of compensatory antithrombotic activities

- Blood viscosity and plasma fibrinogen levels

- Platelet aggregability

- Unstable angina --> ST depression due to plaque rupture but no myocyte necrosis

- NSTEMI --> Some myocyte necrosis but no ST elevation

- STEMI --> Transmural infarction --> ST elevation and high prevalence of arrhythmias

- Thromboembolism --> Disrupted or eroded plaque

- Non-plaque associated coronary thromboembolism

- Dynamic obstruction (vasospasm) of epicardial or microvascular vessels

- Progressive mechanical obstruction to flow

- Coronary artery inflammation (vasculitis)

- Secondary unstable angina

- Coronary artery dissection

- All except thromboembolism are NOT acute coronary syndrome

- Myocyte necrosis occurs within 5-20 minutes of occlusion/infarction

- Area become hypokinetic and then akinetic

- The portion of the wall then begins to bulge and weaken in hours to days

- Rest of the heart becomes hyperkinetic to compensate

- Results in hypertrophy and remodeling of the heart over days to months

- History: Chest discomfort, sudden death, ventricular arrhythmia, SOB, N/V, diaphoresis, weakness/syncope, mild fever and anxiety/impending doom

- Atypical/silent MI: More common in the elderly and women (~20%)

- ECG Changes for STEMI: ST elevation (acute), ST elevation with decreased R wave and Q wave (hours), T wave inversion and deeper Q wave (1-2 days), normal ST and inverted T (days), and only Q wave persists (weeks)

- ECG Changes for NSTEMI: ST depression or T wave inversion

- Serum biomarkers: creatine kinase and troponin

- Unstable angina

- Pericarditis

- Aortic dissection

- Costochondritis

- Musculoskeletal pain

- Gastrointestinal pain

- Pulmonary embolus

- Pleuritis

- Pneumonia

- Anxiety

- All must be considered in the DDx

1. Troponin: 95% increase from normal and present within 2-6 hours of symptoms --> Stays up for a while

- Very specific and allows for early diagnosis

2. Creatine kinase MB (CK-MB): Takes longer to go up but decreases after a couple of days

- Not specific but can quantify damage (severity)

- Late diagnostic tool

- Can diagnose re-infarction

- Normal or ST depression during event

- ST segments and T waves go back to normal weeks later

- No Q waves present in this case

1. Typical rise and fall of biomarkers for necrosis with at least one of the following symptoms:

- Ischemic symptoms

- Pathologic Q waves on ECG

- Ischemic ECG changes --> ST depression/elevation

- Coronary intervention

OR

2. Pathologic findings of an acute MI --> Wall thinning at infarction site with hypertrophy around the site

- Stabilize hemodynamics and rhythm

- Relieve ischemic pain

- Decrease myocardial oxygen demand

- Increased myocardial oxygen supply and coronary perfusion

1. Thrombolysis: tPA works to chemically break up clot --> Bleeding risk associated and only works within 12 hours of onset of symptoms --> Reduced mortality, improved LVF, reduced CHF, and reduced arrhythmias

2. Percutaneous Coronary Intervention (PCI): Catheter threaded up the femoral or carotid artery to the coronary vessel that is occluded --> Balloon expanded or stent placed to reperfuse tissue

- PCI is better if available quickly and at a good center

- Significantly reduced mortality --> Down to 5%

- PCI indicated in pts <75 years old showing signs of cardiogenic shock to reduce mortality

- 40 min: Small zone of necrosis surrounded by ischemic but viable tissue

- 3 hours: Larger zone of necrosis surrounded by a smaller ischemic but viable region

- 24 hours: Largest zone of necrosis --> Will not extend more but also will not regress --> Necrosis complete

- Medically manage initially

1. Asprin --> Gold Standard for treatment (325 mg initially and then 81 mg daily dose) --> 20-25% reduction in mortality

- Often administered with clopidogrel as well for increased anti-platelet therapy

2. Morphine, nitrates and O2 --> Relieve pain and reduce HR and BP but no real change in mortality

3. B-blockers --> Reduce O2 demand, counteract catecholamine effect, reduce arrhythmia risk, redirect blood flow to subendocardium, reduce recurrent ischemia and reduce cardiac rupture

4. Heparin or LMWH --> Anti-coagulant

1. Ca channel blockers (vasodilation) --> Reduce O2 demand and increase O2 supply --> Reduce afterload, slightly reduce preload and contractility

2. ACE Inhibitors --> For pts with diabetes, pulmonary congestion, LVEF <40%, hypertension and CHF

3. ARBs --> Patients who are intolerant of ACE inhibitors and have HF or LVEF <40%

- Determine whether patient should go to cath lab

- Must have 3 or more of these to be considered high risk

1. Age >65 years

2. 3 or more CAD risk factors

3. Prior CAD --> Restenosis of previous PCI within 6 months

4. ASA in last 7 days --> Clot is resistant to one anti-platelet agent

5. 2 or more anginal events in the last 24 hours --> Progression of disease

6. ST deviation

7. Elevated cardiac markers

- High risk: GPIIb/IIIa inhibitor and coronary angiography

- Low risk: Medically manage and perform stress testing

1. Invasive strategy

- Recurrent angina/ischemia at rest

- High risk findings on stress test

- Hemodynamic instability

- Signs/symptoms of HF or new/worsening mitral regurgitation

- LVEF <40%

- PCI within 6 months

- Sustained ventricular tachycardia

- Elevated cardiac biomarkers

- New ST segment deviation

- High risk score (3 or more)

2. Conservative strategy

- Low risk score

- Patient preference in the absence of high risk factors

- Recurrent ischemia --> Post MI angina or reinfarction/infarction extension

- Pericarditis

- Post Myocardial Infarction Syndrome (Dressler's Syndrome)

- Thromboembolism

- Ventricular fibrillation

- Ventricular tachycardia

- Accelerated idioventricular rhythm

- Atrial fibrillation

- Sinus tachycardia

- Sinus bradycardia

- AV nodal heart block/bundle branch block

- When LVEF <40% --> ICD implanted to prevent arrhythmias

1. Left ventricular pump failure --> Loss of muscle mass due to infarction

2. Cardiogenic shock --> Heart can't pump to provide adequate perfusion throughout the body

3. Right ventricular infarction --> RV can't pump enough into lungs and into LA --> Shows sign of right sided HF without any signs of left sided HF (pulmonary edema)

4. Myocardial rupture --> Ventricular-septal defect, papillary muscle rupture, and left ventricular free wall rupture (pseudoaneurysm/cardiac tamponade)

- Education: nitroglycerin use, symptoms of recurrent ischemia, diet, optimal weight, exercise, and smoking cessation

- Smoking cessation --> 50% decreased risk of recurrent symptoms if you quit smoking!!

- Explain the importance of medical compliance especially with aspirin/clopidogrel

- BP target --> 130/85

- Statin to lower LDL to <70 mg/dL

- Diabetics: HbA1C <7.0%

- Arrange follow up appointment with internist and cardiologist

- Encourage patient to enroll in cardiac rehabilitation program

- Major criteria: Carditis, polyarthritis, chorea (St. Vitus dance), erythema marginatum, and subcutaneous nodules

- Minor criteria: Fever, arthralgias, previous ARF, positive acute phase reactants (ESR,CRP), Prolonged PR interval

- Thickening of mitral or aortic valve leaflets

- Most commonly mitral valve involvement

- Inflow stenosis: Increased venous pressure leading to ventricular diastolic filling dysfunction

- Inflow regurgitation: Increased ventricular volume leading to systolic dysfunction (volume overload)

- Outflow stenosis: Increased ventricular pressure leading to diastolic/relaxation dysfunction

- Outflow regurgitation: Increasd ventricular volume leading to systolic dysfunction (volume overload)

- Inflammation and edematous reaction in the valve leaflets and chordae tendinae

- Hyaline vegetations along the line of the closure of the valve result

- Hyaline deposits heal by fibrosis and calcification

- Fusion of the valvular commissures --> Classic fish mouth appearance

- Valvular stenosis and chordal thickening

- Frequently results in mixed stenosis and regurgitation

1. Severe MS sounds and location

- Base: Abnormally loud S1 and shorter S2-OS interval

- Apex: Crescendo, presystolic murmur, loud S1, S2 and OS sounds, with mid-diastolic murmur

- Inspection: JVP is a-wave (S1) dominant

2. Loud S1 sound --> Increased LA pressure and late closure of mitral valve

3. Opening snap --> Mitral valve opens earlier than normal and louder

4. Mid-diastolic murmur --> Corresponds with LA-LV gradient

5. Heart sounds and HR --> Louder S1 sound with increased HR and shorter MDM and PSM with increased HR

- Etiology: Rheumatic fever

- Issues due to increased LA pressure

- Pulse: Often Afib and tachycardia predisposes to CHF

- Increased JVP

- Left and right sided failure result due to volume overload

- Palpable pulmonic component of S2 because pulmonic valve closes later

- Medical: Diuretics, B-blockers (HR), and anticoagulation for Afib

- Surgical: Valvular replacement

- Precutaneous baloon valvuloplasty --> Balloon used to expand the lumen of the stenotic valve

- Acute: Papillary muscle rupture due to MI, myxomatous degeneration (MVP), and endocarditis

- Chronic: Rheumatic, MVP, endocarditis, lupus/RA, degenerative, idiopathic, and secondary to LV remodeling

1. Prolapse: Mid-systolic click

2. Acute: Loud S1, initiates explosive systolic murmur and S3 sound --> Brief pauses between S1 and S2 and murmur

3. Chronic/compensatory: Blowing holosystolic murmur and mid-diastolic rumble due to increased LA and LV compliance

- Inspection: Apex beat is displaced, rocking of stethoscope by LV and left subcostal heave (RV)

- Auscultation: Explosive ESM after S1, isolated S2, and thudding/rumbling S3

- Inspection: Apex beat displaced to 7th lateral intercostal space (7LICS) and outward excursion of stethoscope head during systole

- Auscultation: Blowing murmur with outward excursion, thudding sound with inward return, holosystolic murmur over LV and S3 sound

- Normal BP

- Issue is LV volume overload --> Dilated LV

- Variable degrees of left and associated right HF

- Possible RVH

- Palpable P2 if PAH present

- Medical: Diuretics, ACE inhibitors (Decrease afterload), and ionotropes

- Surgery: MV repair or replacement

- Congenital: Bicuspid, monocuspid, subvalvar and supravalvar issues

- Acquired: Rheumatic and degenerative/atherosclerotic

- Aortic root: Marfans syndrome, degenerative, hypertension, aneurysm, dissection and syphilis

- Aortic valve: Congenital and acquired

- Acute vs. late presentations

- Leads to LVH

- Symptoms: Angina, CHF and syncope (late)

- Increased LV-Ao pressure gradient --> Systolic murmur

- Gradient determined through doppler

- Later peak of murmur --> Larger gradient

1. Chronic: MSM and EDM (base) and Austin Flint and split S1 (apex)

2. Acute: MSM and abbreviated EDM (base) and Austin Flint and absent S1 (apex) --> Leads to tachycardia with loud S2 sound --> Quincke's pulse seen in fingernails 

- Volume overload is the issue

- Chronically well tolerated but can result in CHF

- Physical exam findings: LV dilation, RV dilation and RVH late, wide pulse pressure, and CHF late

- Medical: Diuretics, ACE inhibitors (decrease afterload), and ionotropes??

- Surgery: Aortic root/valve replacement

- Due to endocarditis

- Complications of endocarditis --> CHF, surgery, emboli, drug failure, abcess, pericarditis, fistulae, neurologic, renal failure, and musculoskeletal

- Present in aortic regurgitation

- Apex: Tachycardia of 110 bpm, dynamic and displaced apical impulse, absence of S1 and triple cadence

- Triple cadence: MSM, S2 initiating a brief EDM, MDM superimposed on EDM (to-fro-FRO)

- Right atrium: 0-7 mmHg

- Right ventricle: 15-25 mmHg/0-8mmHg

- Pulmonary artery: 15-25mmHg/8-15mmHg

- Pulmonary capillary wedge pressure: 6-12 mmHg

- Left atrium: 6-12 mmHg

- Left ventricle: 90-140mmHg/60-90mmHg

- Management of complicated MI

- Define etiology of respiratory distress

- Determine etiology of shock

- Assess efficacy of medical management

- Intraoperative monitoring

- Evaluation of cardiac tamponade

- Assess valvular heart disease

- Fluid management

- Pneumothorax

- Hemothorax

- Tracheal perforation

- Sepsis

- Hematoma

- Thrombosis

- Right ventricular perforation

- Arrhythmia

- Heart block

- PA rupture

- Pulmonary infarction

- Bernoulli equation: Q= Change in P/R

- Can help determine stenotic or regurgitant valves

1. Evaluation of CO

- Fick Principle: CO=O2 consumption (Hb content)/(A-V O2 difference)

- Thermodilution Method: Temperature over time --> Determines CO in L/min (5 L/min normal)

2. Evaluation of Resistance

- Systemic: (Mean AoP-Mean RAP)(80)/CO

- Pulmonary: (Mean PAP-MeanPCWP)(80)

- Allows for mixing of oxygenated and deoxygenated blood

- Any O2 % change of 7 or more --> Shunt

- Step up seen on right heart and step down seen in left heart --> Small step down for left heart

- Look for where exactly the step-up is to determine where the shunt is

- Reentry: Most common mechanism. Involves a circuit around which the impulse travels around and around

- Enhanced automaticity: Accleration in the rate of impulse generation of an ectopic focus --> Becomes the dominant pacemaker if the rate is faster than the SA node

- Triggered activity: Uncommon mechanism in the human heart

- Early premature P wave preceding a premature QRS complex

- P wave morphology is different from normal

- May be unifocal or multifocal

- Pause after the PAC of variable duration --> 2PP or 1PP interval

- Atrial bigeminy --> Every other QRS complex is a PAC

- Atrial trigeminy --> Every third QRS complex is a PAC

- Atrial rhythm: Rate <100

- Atrial tachycardia: 100-220 bpm

- Distinct P waves are uniform in morphology but different from sinus rhythm

- PR interval is constant and may even be the same as sinus rhythm

- Isoelectric baseline between P waves

- QRS intervals may be regular or regularly irregular based on extent of AV block in atrial tachycardia

- Rate of 260-320 bpm --> May be slowed with antiarrhythmic drugs

- Flutter waves: Neg/pos in leads II, III and aVf --> Uniform morphology, amplitude and interval

- No isoelectric baseline between flutter waves

- Sawtooth wave pattern

- QRS intervals are regular or regularly irregular based on extent of AV block

- Rate of 320-450 bpm or more

- No organized atrial activity or distinct P waves

- Irregular in morphology, amplitude and interval

- Coarse with recent AF and fine with chronic AF

- QRS intervals are irregularly irregular --> HR depends on AV nodal conduction (up to 170 bpm)

- No P wave infront of QRS complex

- Inverted P wave may be present due to retrograde activation

- QRS intervals are regular

- QRS morphology similar to that of sinus rhythm

1. Junction rhythm --> Rate <100

2. Junctional tachycardia --> Rate >100

3. Atrioventricular nodal reentrant tachycardia (AVNRT) --> Rate 140-220 bpm --> Usually no retrograde P waves seen --> P wave may be superimposed on the end of the QRS complex as R' or S wave

- Early wide QRS complex (>0.12s) without a preceding P wave

- Retrograde P wave possible

- Most commonly followed by a compensatory pause --> 2 PP intervals --> 1 PP interval possible (interpolated)

- Pause depends on whether the signal retrogradely activates the AV node

- May be uniforcal or multifocal

- Ventricular bigeminy --> Every other QRS is a PVC

- Ventricular trigeminy --> Every third QRS is a PVC

- Rate <60 bpm

- Accelerated Idioventricular rhythm --> Rate 60-100 bpm

- QRS complexes wide (>0.12s) and abnormal

- P wave dissociated from QRS complexes --> Often no P waves seen

- Negative P wave possible --> VA conduction

- QRS complexes and ST-T waves may show non-rate related variability in morphology

- Fusion or captured (Dressler) beats may be seen

- Rate >100 bpm

- Nonsustained (NSVT): >3 sequential ventricular beats lasting less than 30 seconds

- Sustained VT (SVT): Sequential ventricular beats lasting more than 30 seconds or until someone intervenes

- Monomorphic: One QRS morphology

- Polymorphic: Variable QRS morphologies

- Torsade des pointes: Polymorphic VT in a patient with baseline QT interval prolongation (prolonged QTc)

- No organized QRS complexes

- Fibrillatory waves irregular in morphology, interval and amplitude

- Commonly leads to sudden death!

1. Class I: Class III/IV angina, high-risk on non-invasive testing, and following cardiac arrest

2. Class IIa: Class III/IV angina that improves to Class I/II with medical therapy, progressively abnormal non-invasive testing, unable to risk stratify, class I/II with intolerance/failure to medical therapy, and specific occupations (pilot)

3. Class III: Angina in patients who are not candidates for revascularization, screening for CAD in asymptomatic patients, and after CABG/PCI in absence of ischemia

1. Stable angina: Class I/II with intolerance to meds and class III/IV for pre-revascularization

2. Acute coronary syndrome

3. Post-MI angina

4. Acute myocardial infarction --> STEMI

5. Markedly positive exercise testing

6. Rule out CAD

1. Defines severity

2. Presurgical study --> Confirm severity, rule out associated diseases, and define coronary anatomy

- PCI procedures --> Balloon valvuloplasty and percutaneous aortic valve replacement

1. Diagnosis

2. Associated lesions

3. Define coronary anatomy

4. Assess physiology

- PCI --> Balloon closure of septal defects

1. Congestive --> Rule out CAD and biopsy of tissue

2. Restrictive --> Assess physiology

3. Hypertrophic --> Assess physiology and define coronary anatomy

- Recent stroke

- Progressive renal insufficiency

- Active GI bleeding

- Fever

- Infection

- Severe anemia

- Uncontrolled hypertension

- Electrolyte imbalance

- Oral anticoagulation

- Decompensated CHF

- Limited life expectancy

- Depends on experience of operator, length of procedure and level of patient acuity

- Major: Death, MI, stroke, and arrhythmias

- Minor: Perforation, coronary dissection, acute renal failure, anaphylaxis

- Pseudocomplications may occur --> During same hospitalization

- Class III/IV angina symptoms

- Change in pattern of angina

- Ischemia on non-invasive testing

- Left ventricular dysfunction

- Diabetes

1. Balloon angioplasty --> High re-stenosis rate

2. Atherectomy

3. Thrombectomy

4. Stents --> Bare or drug-eluting --> Reduced re-stenosis

- Eliminate vessel recoil that contributes to the re-stenosis

- Drug eluting stents don't endothelialize as quickly as bare --> Thrombotic risk

- Diabetes mellitus

- Chronic kidney disease

- Completeness of revascularization

- LV systolic dysfunction

- Previous CABG (for multivessel disease)

- Ability to comply with and tolerate treatment

- Inflammation of the myocardium --> Can be infectious or non-infectious/autoimmune

- May involve myocytes, interstitium, vascular elements or pericardium

- History: Viral prodrome, asymptomatic, palpitations, and chest pain --> Can lead to acute CHF

- Physical Exam: HR >100 bpm, laterally displaced PMI, mitral/tricuspid regurg., and evidence of embolisms

- Active myocarditis: Lymphocytic infiltration with myocytolysis on LM

1. Infectious

- Viruses

- Bacterial

- Mycoplasma

- Protozoa

- Parasites

- Fungus

- Varicella

- Rickettsia

- Spirochetes

2. Non-Infectious

- Drugs

- Hypersensitivity states --> Lupus or Rheumatic Fever

- Radiation

- Heavy Metal --> Cobalt

- Insect stings

1. Diagnosis

- EKG: Non-diagnostic ST-T wave changes, arrhythmias, Q waves and conduction delays

- CXR: Normal, LV dilation or pulmonary congestion

- TnI/CPK-MB serum levels

- Viral studies/PCR

- Radionuclide studies

- CMRI

- Endomyocardial biopsy --> Gold standard for definitive

2. Treatment: Treatment of infection or immunosuppressive therapy for non-infectious causes

- Supportive: Bedrest, reduce afterload, inotropes, antiarrhythmics/anticoagulation

- Complete recovery

- Relapses after months-years

- Recovery with mild residual symptoms

- Chronic myocarditis --> CHF

- Sudden death

1. Primary --> Dilated, hypertrophic, or restrictive --> Idiopathic

- Also arrhythmogenic right ventricular cardiomyopathy --> Very rare

2. Secondary/Specific --> Ischemic, valvular, hypertensive or arrhythmic

- Other: Toxins (cocaine/ETOH), infectious, non-infectious, post-partum, metabolic (diabetic), and endocrine

3. Genetic --> Neuromuscular diseases and familial --> Over 26 genes associated

- Decreased systolic cardiomyopathy --> Reduced ejection fraction

- Dilation/increased left ventricular volume

- History: Asymptomatic, left sided or right sided failure

- Physical exam: Left heart failure (rales, lateral PMI, S3, S4, holosystolic murmur) and right heart failure (JVD, hepatomegaly, and right sided S3)

- Diagnosis: CXR, EKG, Echo, coronary angiography/CT angio, and endomyocardial biopsy

- Mortality: 24% at 1 year --> 57% at 5 years untreated

- Treatment: ACE-I/ARB, B-blockers, diuretics, digoxin, nitrates, antiarrhythmics, anticoagulants, LVAD, or transplant

- "Broken-heart" cardiomyopathy

- Catecholamine mediated reversible cardiomyopathy

- Stress induced --> Surge of catecholamines --> Apical ballooning of ventricle --> dilated cardiomyopathy

- Totally reversible if stress removed

- Myofibril disarray with hypertrophy of the interventricular septum --> Can lead to outflow tract obstruction

- Decreased ventricular compliance --> Reduced filling capacity

- Ischemia from inefficient ATP use, intimal thickening of coronary arteries, and supply/demand mismatch

- Leads to excessive fibrosis/myopathy/CHF

- Ventricular ectopy also possible

- History: Sudden cardiac death in children/athletes, symptoms of CHF, and arrhythmias

- Physical exam: Brisk upstroke in carotids, double impulse PMI with S4, systolic murmur with outflow obstruction and holosystolic murmur from MR

- Increased incidence: Reduced ventricular volume when sitting upright or doing Valsalva or increasing contractility with exercise or digitalis

- Decreased incidence: Increasing ventricular volume by lying down or reducing contractility with B-blockers or cardiac depressants

1. Diagnosis: CXR, EKG, Echo, or cardiac cath (exclude CAD, etc)

2. Therapy: B-blockers, Ca-channel blockers, antiarrhythmics, pacing from RV, septal artery ablation, myomectomy, and genetic counseling

- Avoid hypovolemia and sympathetic stimulation

- Cautious diuretic use

- Arrhythmias: Ventricular or atrial and sinus bradycardia/arrest

- Hemodynamics: Left ventricular outflow obstruction

- Abnormal diastolic function due to infiltration

- Systolic function is normal initially but becomes progressively worse with infiltrations

- Presentation mimicks constrictive pericarditis

- Endomyocardial causes: Fibrosis, Loeffler's CMP, hypereosinophilia, radiation, and tumors

- Myocardial: Infiltrative diseases (amyloidosis/sarcoidosis), and storage diseases

- Monoclonal antibody in urine or serum

- Results in: nephrotic syndrome, hepatomegaly, carpal tunnel syndrome, macroglossia, malabsorption/diarrhea, peripheral neuropathy, and cardiomyopathy

- History: Heart failure (SOB), palpitations, arrhythmias, and symptoms of underlying disease

- Physical Exam: JVD, S3 and regurg., rales, and pulmonary edema

1. Diagnosis: CXR, EKG (low voltage), echo (thick walls), catheterization, and endomyocardial biopsy

2. Treatment: Depends on underlying disease, bone marrow and heart transplant for amyloidoses and supportive care

- Non-organized re-entrant wavelets

- Symptoms: None, irregular/skipping heartbeat, palpitations, fatigue, exercise interolerance, lightheadedness, dyspnea, anxiety, and angina

- Risk factors: Age, sleep apnea, hypertension, diabetes/obesity, MI and CHF

- Consequences: Thromboembolism and tachycardia

- Paroxsymal: Recurrent (>2 episodes) with spontaneous termination within 7 days

- Persistent: Sustained beyond 7 days

- Long-standing persistent: Continuous for >1 year

- Permanent: Cardioversion failed

1. B-blockers and Ca channel blockers to slow AV conduction

2. Anti-coagulation for most patients but not all!

- Anti-coagulation depends on CHADS2 score and thromboembolism risk

- Risk is greatest for patients with prior stroke/TIA, diabetes, hypertension and CAD

- CHADS-2 score >2 --> Anti-coagulation therapy with warfarin

- New anti-coagulants --> Dabigatran, rivaroxaban, and apixaban --> No INR monitoring and standard dosing

3. Direct current cardioversion --> Works very well temporarily but Afib almost always comes back

4. Anti-arrhythmic drugs --> Amiodarone, flecainide, and sotalol

- LA appendage occlusion device --> Signficantly decreases thromboembolism risk

- Catheter ablation/cautory surgeries --> Cut the atrial into multiple different sections to minimize number of wavelets possible

- Maintained by multiple circulating wavelets of activation --> >6

- Critical mass of wavelets must be maintained to perpetuate AF

- Higher wavelength --> Slow conduction and short refractoriness --> Multiple wavelets possible

- More possible in dilated/enlarged atria

- Adds onto substrate hypothesis

- Pulmonary veins create their own electrical impulse that can extend into the atria and perpetuate wavelets

- These PV impulses drive Afib

- Surgical cautory of connection between the atria and pulmonary veins --> Helps stop early Afib --> Doesn't work for late Afib

- 8/1000 live births --> Most common birth defect

- Risk factors: Genetics, environment, maternal illness (diabetes) and toxin exposure

- ~85% of infants with CHD will reach adulthood --> Adult congenital heart disease

- Day 15: Two separate endocardial tubes

- Day 21: Tubes fuse --> RA/LA, LV, RV, CT, and AA from inferior to superior

- Day 28: Folding and twisting begins --> RV becomes bound to CT --> PA and LV becomes bound to AVV and AS --> Aortic arch

- Day 50: Mature heart with intact valves and papillary muscles should be present

1. Septum primum grows towards the endocardial cushion --> Ostium primum develops

2. As septum primum grows towards endocardial cushion to obstruct ostium primum, ostium secundum begins to form via apoptosis

3. Septum secundum grows down over the ostium secundum to partially occlude and develop valve

4. Septum primum becomes the valve of the foramen ovale

- Oxygenation through the placenta NOT lungs

- Ductus venosus --> Bypasses the liver and dumps directly into IVC --> Carries high O2 content blood and preferentially passes through PFO

- Patent foramen ovale (PFO) --> Supply of blood flow to LA from RA

- Patent ductus arteriosus --> Between PA and aorta --> Flow bypasses the lungs and enters directly into ascending aorta

1. Foramen ovale closure

- Increased pulmonary flow due to decreased resistance

- Increased LA pressure and decreased RA pressure

2. PDA closes

- Decreased PGE1 production --> Vasoconstriction occurs

- Increased PaO2

3. Ductus venosus closes

- Blood flow from placenta decreases --> Closure due to decreased flow

- Result in decreased pulmonary blood flow

- Right to left shunting occurs

- Bluish discoloration of the skin --> O2 sat of 80-85%

- Intracardiac vs. intrapulmonary shunt

1. Tetralogy of Fallot/Pulmonary atresia

2. Transposition of great arteries

3. Tricuspid atresia

4. Truncus arteriosus remains --> Single outflow

5. Total anomalous pulmonary venous return

6. Eisenmenger syndrome --> Increased pulmonary vessel vasculature --> Increased resistance and RHF --> Leads to right to left shunt

- Left to right shunting occurs --> Pulmonary overcirculation occurs

- Obstructive causes --> Right or left sided

1. Ventricular septal defects

2. Atrial septal defects

3. Patent ductus arteriosus

4. Aortopulmonary window

5. Atrioventricular septal defect --> Endocardial cushion

6. Left-transposition of great arteries

- 5-10% of CHD cases --> Secundum (50-70%) and primum (30%), and sinus venosus defect (10%)

- Most common CHD in adults

- Patent foramen ovale --> 20% of general population

- Left to right shunt

1. Partial Anomalous Pulmonary Venous Return --> Associated with sinus venosus type --> Some PVs return to RA instead of LA --> RA dilation

2. Mitral valve prolapse is common with secundum type

3. Lutembacher syndrome: ASD and mitral stenosis  

- Murmur: Systolic murmur due to pulmonary stenosis or volume overload of the RV

- Complications: Depends on size, volume/pressure overload, exercise intolerance, atrial arrhythmias, PAH, paradoxical embolism, and RHF (late)

- Treatment: Open heart surgery via pericardial patch or transcatheter closure for secundum ASDs

- Most common CHD in children --> ~20% of CHD

- Types: Inlet, membranous (70%), muscular (20%), outlet or supracristal

- Left to right shunt

- Murmurs: Fixed split S2 sound, systolic murmur and mild diastolic rumble possible depending on location --> Larger defects don't have any murmur

- Complications: LA and ventricular dilation, CHF, aortic valve prolapse or regurgitation, PAH, atrial arrhythmia, endocarditis, and Eisenmenger syndrome

- Treatment: endocarditis antibiotic prophylaxis, surgical repair with minimally invasive surgery, and transcatheter closure

- 1/2500-1/5000 live births --> 5% of CHD

- Risk factors: Prematurity, maternal rubella, and high altitude births

- Left to right shunt

- Pulmonary overcirculation

- Can be silent

- Murmur: All of systole and most of diastole

- LA and ventricular volume overload

- Atrial arrhythmias/dyspnea

- PAH or Eisenmenger's syndrome

- Differential cyanosis/hypoxemia --> High O2 content for head and UE while low O2 content for LE

- Endarteritis --> Prevalence increases with age

- Treatment: Thoracotomy, coil occlusion, or PDA device/plug to block PDA

- Most infants with CHD have no risk factors

- 1985: 4 chamber view on echo to improve accuracy of screening

- 1992: Incorporate outflow tract views to improve accuracy of screening

- Increased upslope of phase 4 due to increased Ica

- If upslope reaches a threshold level --> Cells depolarize

- Anti-arrhythmics --> Reduce slope of phase 4 depolarization --> Decrease automaticity by blocking Ca

- Delayed After Depolarization: Reactivation of Na channel depolarization due to spontaneous leak of Ca from SR

- Early After Depolarization: Due to reactivation of L-type Ca channel and/or Na/Ca exchanger --> Triggers another action potential

- EAD can easily lead to torsades de pointes in patients with prolonged QT intervals

- Anti-arrhythmics decreased triggered activity by reducing Ca currents and stabilizing resting membrane potential

- Most common cause of arrhythmia

- Only occurs in patients with slow and fast conduction pathways through the heart

- Slow pathway --> Slow conduction with short refractory period --> Allows for closely coupled impulses

- Fast pathway --> Fast conduction with long refractory period --> Impulses must be dispersed based on refractory period

1. Sinus impulse travels down fast pathway

2. Premature beat cannot travel down fast pathway because it's already depolarized --> Travels down slow pathway

3. By the time the impulse of slow pathway reaches the intersection of the slow and fast pathways, fast pathway has refracted --> Retrograde/anterograde impulse up fast pathway that allows for re-entry into circuit

- Anti-arrhythmic drugs slow impulse conduction and increase refractory period of slow pathway --> Prevents re-entry into circuits

- Na channel blockers

- Class Ia --> Intermediate dissociation --> Procainamide

- Class Ib --> Fast dissociation --> Lidocaine --> Acute and IV only

- Class Ic --> Slow dissociation --> Flecainide --> PO administration --> Used for structurally normal hearts

- Normally dissociate from channel when channel is closed

- Flecainide can precipitate functional bundle-branch or AV node block --> Slows His/Purkinje conduction

- Work better at higher HRs

- Mostly atrial arrhythmias --> Can precipitate Atrial Flutter though

- B-blockers --> Metoprolol

1. Reduces automaticity by reducing slope of phase 4 depolarization

2. Reduces reentry through AV node by prolonging phase 3 --> increased refractory period

3. Reduced triggered activity by reducing Ca currents

- Uses: Atrial and ventricular arrhythmias

- Side Effects: Hypotension, bradycardia, heart block, fatigue, depression, erectile dysfunction, and negative iontropy

- Contraindications: SA node dysfunction, cardiogenic shock and severe hypotension

- K channel blockers --> Prolonges repolarization by blocking outward K current

- Decrease the excitable gap by increasing refractoriness of the tissue --> head meets the tail and extinguishes arrhythmia

- Works best on slower HRs --> Increased prolongation

- *Dofetilide*, sotalol (II&III), and amiodarone (I,II,III,&IV)

- Amiodarone is the drug of choice for abnormal hearts

- Side effects: Torsades de pointes with QT prolongation

- Uses: Atrial & ventricular arrhythmias

- Ca channel blockers --> Verapamil --> Heart specific

1. Reduces HR by increasing threshold of SA node

2. Reduces AV node conduction by prolonging phase 0 and phase 3

3. Reduces triggered activity by reducing Ca currents

- Uses: Atrial & ventricular arrhythmias

- Side effects: Hypotension, bradycardia, heart block, negative inotropy, dizziness, headaches and constipation

- Contraindications: SA node dysfunction, heart failure and hypotension

- Reduces cAMP levels and reduces Ica

- Only IV administration

- Uses: Termination of atrial arrhythmias (SVT)

- Pharmacokinetics: Very short half-life

- Mechanism: Slows AV node conduction and reduces spontaneous depolarization of the SA node

- Side effects: Hypotension, heart block, prolonged asystole, bronchoconstriction, flusing, CP and SOB

- Contraindications: 2nd or 3rd degree heart block, SA node dysfunction (hypersensitivity)

- Inhibits Na/K ATPase

1. Reduce automaticity by reducing slope of phase 4

2. Reduce reentry through AV node by prolonging phase 4 and phase 0

3. Positive inotropic effect by increasing cytosolic Ca

4. Increased vagal tone

- Uses: Atrial arrhythmias

- Administration: IV or PO

- Pharmacokinetics: 80% bioavailability and renally excreted

- Side effects: Atrial & ventricular arrhythmias, bradycardia, heart block, N/V, dizziness, confusion, delirium, and visual disturbances

- Contraindications: Heart block, cardiomyopathy due to amyloid, RCM, CCM or HCM

- Presents with N/V, dizziness, and yellow halos in visual fields

- PHx: Hypertension and mild renal impairment --> Reason for toxicity

- Auscultation: Regular by tachycardic rhythm

- Labs: High Cre (4.5), low K (2.3), and high digoxin (3.8)

- EKG: Retrograde P waves seen --> Enghanced automaticity or triggered activity cause retrograde P

- Characteristic arrhythmia due to mitral or aortic valve surgery, digoxin toxicity, ARF, lyme, inferior infarction with ischemia to AV node, and increased adrenergic tone

- Side Effects: Atrial & ventricular arrhythmias, bradycardia, and heart block

- Symptoms are exacerbated by hypokalemia

- All due to decreased AV nodal activity from ischemia, infection or toxicity --> Usually benign though

- Most common type of SVT (60%) --> 2:1 female to male prevalence 

- PHx: Palpitations that initiate with skipped beat and lasts for 10-30 minutes

- Vitals: HR 184 bpm and BP 98/52

- Cannon A waves in JV --> Contraction of A&V against closed tricuspid valve

- AVNRT --> P wave superimposed on QRS complex (~R')

- Simultaneous activation of the atrium and ventricle

- Treatment: Carotid sinus massage to stimulate vagal tone then adenosine --> Metoprolol for discharge and referral for catheter ablation

- PHx: Symptoms following exercise, syncope due to palpitations

- Vitals: HR 220 bpm and BP 112/68 mmHg

- Retrograde P wave superimposed on T wave

- Circuit: AV node --> Ventricle --> Accessory pathway --> Atria --> AV node

- Retrograde conduction or concealed conduction resulting in normal QRS pattern

- Treatment: Amenable to AV nodal blockers without WPW syndrome then catheter ablation

- Circuit: Accessory Pathway --> Ventricle --> AV node --> Atria --> Accessory pathway

- Anterograde/manifest conduction resulting in Delta wave --> Myocardium depolarized directly from accessory pathway

- Presents at Wolf Parkinson White Pattern on EKG

- Treatment: Amenable to AV nodal blockers without WPW syndrome then catheter ablation

- 0.1-0.3% of population

- Short PR interval, delta wave, and ORT or ART tachycardia on EKG

- Symptoms: Palpitations, SOB, CP, presyncope and syncope

- Sudden cardiac death possible but rare

- Due to rapid anterograde conduction of atrial fibrillation over the accessory pathway

- Treatment: Avoid AV nodal blockers (promotes AP conduction), IV procainamide to slow AP conduction (only indication), cardioversion, and refer for catheter ablation

- PHx: Palpitations and near syncope

- Vitals: HR 190 bpm and BP 82/52 mmHg

- Most often due to a reentrant mechanism --> Post MI or some other mechanism causing scaring (structurally abnormal hearts)

- Wide QRS complex (>0.12s) --> V-A dissociation often present

- Can easily degenerate to Vfib --> Sudden death!

- Causes: HCM, sarcoidosis, arrhythmogenic right ventricular dysplasia and repaired tetralogy of Fallot

- Treatment: Catheter ablation and ICD implantation

- PHx: Syncope, sotalol for Afib control, hypertension and renal dysfunction

- Vitals: HR 42 bpm and BP 185/94

- Often seen with prolonged QT interval --> Prolonged repolarization leading to after polarizations (triggered activity)

- Acquired Long QT: Sotalol, erythromycin and antihistamines

- Congenital Long QT: Mutations in K channel

- Leads to torsades de pointes --> Life threatening!

- Treatment: Cardioversion, removal from meds if med induced, and ICD implantation

1. Peripheral Arterial Disease: Intermittent claudication, critical limb ischemia, and acute limb ischemia

2. Aortic aneurysmal disease

3. Aortic dissection

1. Atherosclerosis --> Most common cause

2. Non-atherosclerotic: Large vessel vasculitis, arterial embolism, extravascular compression, fibromuscular dysplasia, adventitial cystic disease, and fibroelastosis

- High prevalence in the US

- Risk factors: Diabetes, smoking, age, hypertension, and total cholesterol

- Increased relative risk for PAD patients with CAD and CHD

- Blood flow determined by pressure gradient

- Resistance ~ 1/R4

- Stenosis of an artery to a critical diameter results in precipitous fall in blood flow

- Also, stenosis leads to reduced vascular responses

- Asymptomatic

- Atypical symptoms

- Intermittent claudication --> Exertional LE pain/discomfort, cramping, and resolves with rest --> Demand exceeds supply with activity

- 

- Pseudoclaudication: Onset with walking/standing, paresthetic, bilateral, present with variable distances, caused by spinal stenosis, and relieved by sitting down or leaning forward

- Claudication: Onset with walking, cramping/aching feeling, not always bilateral, present with constant distances, caused by atherosclerosis, and relieved by standing still

- Exam: Diminished/absent peripheral pulses, bruits, evidence of atherosclerosis, hair loss on skin, color changes, ulceration, and measurement of ankle pressures

- Diagnosis: Ankle brachial index, segmental pressures, pulse volume recording, duplex imaging and doppler analysis, transcutaneous oxygen, exercise testing, CT/MR angiography and contrast angiography

- Determine the arm, posterior tibialis and dorsalis pedis pressures on both sides

- Right ABI: Higher right ankle pressure/higher arm pressure

- Left ABI: Higher left ankle pressure/higher arm pressure

- Normal: <0.9

- Mild obstruction: 0.81-0.90

- Moderate obstruction: 0.41-0.80

- Severe: 0.00-0.40

- Prevent ischemic cardiovascular events

- Slow the progression of atherosclerosis

- Improve tissue viability and promote healing

- Provide relief from the symptoms of intermitten cladication

- Risk Factor Modification: Quit smoking, reduce LDL <100 mg/dL, reduce BP <130/85 mmHg, and reduce HbA1C <7%

- Treatment: Aspirin or clopidogrel (antiplatelet)

- Exercise therapy --> Goal is to increase the time until symptoms appear and have to stop exercising --> Walking plan

- Medications: Pentoxifylline and Cilostazol

- Revascularization: Really only used for patients with really severe symptoms --> For patients who fail meds or exercise therapy

- Exercise therapy showed the greatest symptom improvement

- Phosphodiesterase III inhibitor

- Improves walking distance in mild to severe claudication

- Dosage: 100 mg twice daily

- Side effects: Headache and GI symptoms

- Contraindications: CHF

- Decreases blood viscosity

- Modest improvement in treadmill walking distance

- Clinical revelance is uncertain --> Limited information on effect on quality of life

- Dosage: 400 mg three times a day

- Side effects: GI symptoms

- Indications for PCI: Claudication that affects quality of life, limb salvage, and vasculogenic impotence

- Indications for Bypass surgery & endoarterectomy: Limb threatening ischemia with pain at rest and intermittent claudication that failed non-surgical treatment