Lecture 28: Relative Risk Factors for and Prevention of Heart Disease

1. Life Expectancy?
a. 70-80 years for most….if trauma or infection doesn’t get you.
b. Unchanged in at least 4000 years!
2. Leading Causes of Death 2014 (as of 2017, so 3 year lag time)
a. Heart disease: 614,348
b. Cancer: 591,699
c. Chronic lower respiratory diseases: 147,101
d. Accidents (unintentional injuries): 136,053
e. Stroke (cerebrovascular diseases): 133,103
f. Alzheimer's disease: 93,541
g. Diabetes: 76,488
h. Influenza and pneumonia: 55,227
i. Nephritis, nephrotic syndrome, and nephrosis: 48,146
j. Intentional self-harm (suicide): 42,773
3. VA and Heart Disease
a. Virginia's death rate from diseases of the circulatory system has fallen every year since 2000. After adjusting for
differences in age, in 2010 there were 227 deaths per 100,000 people in Virginia and 236 in the nation, giving
Virginia the 25th lowest rate in the country.
b. Cardiovascular death rates also continue to fall across much of the state.
c. In 2011, the Northern, Valley, and Central regions of Virginia had the lowest age-adjusted death rate for major
cardiovascular disease, with 157, 207, and 217 deaths per 100,000 people, respectively.
d. The Southside region again had the highest rate in 2011, with 299 deaths per 100,000 people.
4. Cardiac Risk Equivalent
a. Symptomatic carotid artery disease
b. Peripheral arterial disease
c. Abdominal aortic aneurysm.
d. AS ESTABLISHED BY NHLBI ★
e. ACC/AHA and NKF all list chronic kidney disease as a CHD risk equivalent.
f. Mild to moderate kidney dysfunction also associated with increased risk
g. Note: not all people come in with chest pain and SOB, but rather complaint that they have to stop and rest more
5. Risk Factors

6. CVD RIsk Factors

a. NON-MODIFIABLE
i. Age
ii. Gender (men > women)
 iii. Family history
iv. Established CVD Disease

b. MODIFIABLE
i. Cigarette Smoking (zero = amt to safely smoke without developing risk of CVD)
ii. Hypertension
iii. Hypercholesterolemia
iv. Low HDL-Cholesterol (HDL cholesterol is the scavenger molecule that mobilizes energy stores)
v. Obesity (more work for your heart)
vi. Diabetes Mellitus
vii. Hypertriglyceridemia
viii. Sedentary Lifestyle (recommendations vary, but 45 mins 5 days a week)
7. Risk Factors for Coronary Heart Disease; AHA
a. Major Risk factors
i. Increasing age - @ 80% of people who die from CHD > 65 yo. women more likely to die than men at old
ages from MI
ii. Gender – men > risk than women even after menopause
iii. Heredity – includes race, Fam Hx counts
iv. Tobacco – 2-3x > than non smokers, secondhand smoke also increases risk
v. Cholesterol – risk increases with > cholesterol
vi. Hypertension – increase heart’s workload
vii. Physical inactivity – regular moderate to vigorous physical activity helps prevent heart and blood vessel
disease
viii. Obesity – increased risk especially midline
ix. DM – risk equivalent
b. Other Contributing Factors
i. Stress either direct or indirect
ii. Etoh – in excess causes ↑ BP, obesity, accidents, CVA, elevated triglycerides; risk is ↓in those who drink
moderately
8. Heart Studies
a. Framingham ★
i. 7733 patients ages 40-94
ii. Helped us define cardiac risk
iii. Note: followed patients for decades to look at cholesterol, BP, how likely they were based on stats to get
CHD
b. Interheart Study – 52 countries nine potentially modifiable risk factors accounted for 90% risk associated with first
MI:
smoking, dsylipidemia,hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits and
vegetables, regular etoh use, regular exercise
9. Risk Differs with Age and Sex
a. DM and low HDL - higher risk in women
b. Smokers- increased risk 6x in women and 3 x in men
c. Age and HTN
10. Age as a Risk Factor
a. CAD increased with age
b. > 45 years of age in men
c. > 55 years of age in women
11. Family History
a. Significant independent risk factor, particularly for younger individuals
 b. Physicians health study ( 22,000 for 13 years) and Womens health Study (40,000 for 6 years) - paternal MI before
age 60 was associated with increased risk and any maternal hx associated with increased risk
c. Framingham offspring study showed increased risk of cardiovascular events if premature CAD was found in
males(father) prior to age 55 and females(mother) prior to age 65; increased risk with siblings also
12. Lipids
a. Randomized trials show decreased risk with lower cholesterol levels; may also be independent risk reduction from
statins
b. Risk increased with elevated LDL, total cholesterol and low HDL
c. Increased total to HDL cholesterol level
d. Hypertriglyceridemia
e. Increased nonHDL chol
f. Increased Lp(a)
g. Increased apolipoprotein B(LDL) and decreased apolipoprotein A-1 (HDL)
h. Small dense LDL
i. Apolipoprotein E genotypes
j. Note: high LDL and low triglycerides = less harmful; low LDL and high triglycerides = more harmful
13. Hypertension
a. Interheart study predicted hypertension was responsible for 18% of risk for first MI
b. SBP and DBP both risks.
c. Duration and degree contribute to risk
d. Higher BP; higher risk
e. More medical problems; more risk
f. Note: if you want to know health problems, ask for medications list
14. Diabetes Mellitis
a. Copenhagen heart study showed increased risk of MI or stroke was 2-3x, and death 2x (independent of other CHD
risk factors)
b. Interheart study DM responsible for 10% risk
c. 2002 NCEP (National Cholesterol Education Program) designated DM a CAD risk equivalent
d. Higher blood glucose levels correlate with increased cardiovascular risk for diabetics and non-diabetics;
e. 1% increase in HgbA1c associated with pooled relative risk of CHD and stroke of 1.18.
15. Obesity
a. Framingham offspring study; adjusting for risk factors increased BMI associated with increased risk of CHD, and
CVD.
b. Metabolic syndrome – abdominal obesity, hypertension, diabetes, and hyperlipidemia; increased risk for CAD
16. Metabolic Syndrome
a. Increased risk for heart disease and DM type 2
b. Evidence from: Kuopio Ischemic Heart Disease Risk Factor Study demonstrated higher rates of coronary,
cardiovascular and all cause mortality
c. Metabolic syndrome defined as 3 of 5 traits and medical conditions ★ know these numbers
i. Elevated waist circumference - Waist measurement of 40 inches or more in men, 35 inches or more in
women **
ii. Elevated levels of triglycerides - 150 mg/dL or higher or taking medication for elevated triglyceride levels
iii. Low levels of HDL (high-density lipoprotein) or good cholesterol - Below 40 mg/dL in men, below 50
mg/dL in women, or taking medication for low HDL cholesterol level
iv. Elevated blood pressure levels - For systolic blood pressure, 130 mm Hg or higher; 85 mm Hg or higher
for diastolic blood pressure; or taking medication for elevated blood pressure levels
v. Elevated fasting blood glucose levels - 100 mg/dL or higher or taking medication for elevated blood
glucose levels[30] (Note: The American Association of Clinical Endocrinologists, the International Diabetes
Federation, and the World Health Organization have other, similar, definitions for metabolic syndrome.)
17. Lifestyle
 a. Exercise – regular exercise has protective effect against CHD and all cause mortality; Interheart study showed lack
of regular exercise had 12 % risk of first MI. Womens Health Initiative study showed 30% reduction in vascular
events
b. Cigarette smoking – increase risk 6X in women and 3x in men (smoking > 20/day). Interheart study showed 20%
PAR (percent added risk) for first MI; benefits of quitting no matter how long or how much smoked
c. Diet- consumption of fruit and vegetables is inversely related to risk of CHD; Interheart study- lack of daily
consumption of fruit and vegetables has PAR of 14%.
d. Etoh - Relative risk reduction in both men and women who are moderate drinkers; Interheart study showed PAR of
7% for non drinkers. Reduced risk from elevation of HDL and antioxidant, antithrombotic, and anti-inflammatory
effects.
e. Psychosocial factors – increased stress , increased risk but may be due to coping factors (smoking, overeating,
increased etoh); strong association between depression and CAD
f. Estrogen deficiency – incidence of CHD increases in women after menopause; Womens Health Initiative and HERS
trial showed no cardioprotective effect for estrogen-progestin replacement and may have been harmful.
18. US vs VA

19. Prevention
a. Stop smoking
b. reduce Etoh
c. BP normal
d. BS under control
e. Physical exercise
f. Normal BMI/ waist circumference
g. Healthy diet – dark colored fruits and vegetables, whole grains, lean meats, avoid excess sugars, avoid trans fats,
hydrogenated fats, and saturated
--Pediatrics --
1. Pediatrics: Metabolic Syndrome
a. Metabolic syndrome defines as 3 of 5 traits and medical conditions ;ages 10-16 age > 16 use adult criteria
i. Elevated waist circumference - Waist measurement of > 90th percentile **
ii. Elevated levels of triglycerides - 150 mg/dL or higher or taking medication for elevated triglyceride levels
iii. Low levels of HDL (high-density lipoprotein) or good cholesterol - Below 40 in boys and girls
iv. Elevated blood pressure levels - For systolic blood pressure, 130 mm Hg or higher; 85 mm Hg or higher
for diastolic blood pressure; or taking medication for elevated blood pressure levels
v. Elevated fasting blood glucose levels - 100 mg/dL or higher or taking medication for elevated blood
glucose levels[30] (Note: The American Association of Clinical Endocrinologists, the International Diabetes
Federation, and the World Health Organization have other, similar, definitions for metabolic syndrome.)
b. Note: acanthosis nigricans ??? growing on neck due to endocrine problem
2. Pediatric CVD Risks
a. Metabolic syndrome
b. Obesity
c. Hypertension
 d. Lipid abnormalities
e. DM- screen with obesity, maternal DM, low birth weight
f. Targeted cholesterol screening:
i. 2-8 years and 12-16
ii. moderate or high risk medical condition
iii. CVD risk factors: DM, hypertension, BMI > or = 95% percentile or smoking
iv. Family hx of early CVD or severe hypercholesterolemia
g. Consider treatment if total cholesterol
i. 200 in children and adolescents
ii. > 225 in young adults ages 20-24
iii. Treatment of choice is statin
h. May 21, 2012 — Thirty-seven percent of normal-weight adolescents had at least 1 risk factor for cardiovascular
disease (CVD), as did 49% of those who were overweight and 61% of those who were obese, according to a study
published May 21 in Pediatrics.
i. Ongoing cross sectional data reported every 2 yrs; looked at CVD risk pre HT or HTN, elevated LDL, low HDL, and
pre DM or DM
-- Cardiac Controversy --
1. NY Times
a. Op-Ed Contributors
b. Don’t Give More Patients Statins
c. By JOHN D. ABRAMSON and RITA F. REDBERG
d. John D. Abramson, a lecturer at Harvard Medical School and the author of “Overdosed America: The Broken
Promise of American Medicine,” serves as an expert in litigation involving the pharmaceutical industry. Rita F.
Redberg is a cardiologist at the University of California, San Francisco Medical Center and the editor of JAMA
Internal Medicine
2. Old vs New Guidelines
a. Old guidelines were recommendations then authors sought evidence
b. New guidelines based on RCTs
c. Cardiac risk calculator has not been studied in RCTs
d. New pooled cohort to base decisions on cardiac risk
e. ARIC Atherosclerosis Risk in Communities
f. CARDIA Coronary Artery Risk Assessment in Young Adults

3. New Cholesterol Guidelines

a. New risk factor threshold to treat at 7.5% evidence? not there; it will increase the number of healthy people for
whom statins are recommended by nearly 70 % **
b. New calculator - validated? not really
c. Primary prevention now focused on statin use, not worried about LDL number anymore
d. Statins as primary prevention will prevent 1-2 heart attacks in 100 people who take drug for 5 years
e. Underestimation of SEs: myopathy, DM, memory loss; @ 20 in 100 will have side effects
4. Statins
a. Chair and Vice Chair of guidelines questionable ties to drug companies
b. The Cochrane review[4] published by Kausik Ray and colleagues in the Archives of Internal Medicine a few years
ago showed little or no mortality benefit for statins in primary prevention.
c. Overall the risks of statins are underestimated, in recent data about 20% of patients at risk for muscle aches and
pains or at risk for diabetes
d. Statins are effective for people with known heart disease. But for people who have less than a 20 percent risk of
getting heart disease in the next 10 years, statins not only fail to reduce the risk of death, but also fail even to
reduce the risk of serious illness —article co-written by one of us. That article shows that, based on the same data
 the new guidelines rely on, 140 people in this risk group would need to be treated with statins in order to prevent
a single heart attack or stroke, without any overall reduction in death or serious illness.
5. Summary
a. Risk calculations are the start of a discussion that should include smoking cessation, diet and exercise
Guidelines don’t write RXs
-- Tools --
1. ASCVD Risk Assessment Tool
a. REGARDS Analysis Answers Critics of New CV-Risk Equations
i. The controversial risk equations recently introduced in the 2013 ACC/AHA guideline on the assessment of
cardiovascular risk may be a more accurate predictor of atherosclerotic CV-disease events than its critics
claim.
ii. When Dr Paul Muntner (University of Alabama at Birmingham) and colleagues applied the "pooled-
cohort" risk equations to a contemporary cohort of people not on statins and without standard statin
indications, its risk predictions were similar to observed event rates. The analysis was reported here, with
simultaneous publication in JAMA. However, Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA)
remains critical: "In the new Rotterdam data and in the reanalysis of the REGARDS data as a whole, the
ACC/AHA calculator overestimated risk and calibrated poorly, quite consistent with prior studies," he told
heartwire.
b. age 20 or older who doesn't already have heart disease or diabetes.
c. By age 40, everyone should know their risk score using this tool and should assess their risk every five years
d. If you have a family member who had heart disease at an early age (mother or sister before age 65, or father or
brother before age 55) you should know about your risk factors and be screened earlier than age 20.
e. Do not use this tool if you already have been diagnosed with heart disease, diabetes, peripheral arterial disease,
abdominal aortic aneurysm or carotid artery disease. You are already at high risk (more than 20 percent) to have a
heart attack or die from coronary heart disease in the next 10 years.

2. ACC Risk Estimation Tool

a. The 10-year calculated ASCVD risk is a quantitative estimation of absolute risk based upon data from
representative population samples.
b. The 10-year risk estimate for "optimal risk factors" is represented by the following specific risk factor numbers for
an individual of the same age, sex and race: Total cholesterol of 170 mg/dL, HDL-cholesterol of 50 mg/dL,
untreated systolic blood pressure of 110 mm Hg, no diabetes history, and not a current smoker.
c. Example: If the 10-year ASCVD risk estimate is 10%, this indicates that among 100 patients with the entered risk
factor profile, 10 would be expected to have a heart attack or stroke in the next 10 years.
d. Lifetime Risk
i. The lifetime calculated ASCVD risk represents a quantitative estimation of absolute risk for a 50 year old
man or woman with the same risk profile.
 ii. This estimation of risk is based on the grouping of risk factor levels into 5 strata.
1. All risk factors are optimal* ★
2. ≥1 risk factors are not optimal†
3. ≥1 risk factors are elevated‡
4. 1 major risk factor§
5. ≥2 major risk factors§
iii. The division of lifetime risk by these 5 strata leads to thresholds in the data with large apparent changes in
lifetime risk estimates.
iv. Example: An individual that has all optimal risk factors except for a systolic blood pressure of 119 mm Hg
has a lifetime ASCVD risk of 5%. In contrast, a similar individual that has all optimal risk factors except for
a systolic blood pressure of 120 mm Hg has a lifetime ASCVD risk of 36%. This substantial difference in
lifetime risk is due to the fact that they are in different stratum.
3. Primary Prevention ASCVD
a. Individuals with LDL-C ≥190 mg/dL or triglycerides ≥500 mg/dL should be evaluated for secondary causes of
hyperlipidemia. (I B)
b. Adults ≥21 ★ years of age with primary LDL-C ≥190 mg/dL should be treated with high-intensity statin therapy
unless contraindicated. For individuals unable to tolerate high-intensity statin therapy, use the maximum tolerated
statin intensity. (I B)
c. For individuals ≥21 years of age with an untreated primary LDL-C ≥190 mg/dL, it is reasonable to intensify statin
therapy to achieve at least a 50% LDL-C reduction. (IIa B)
d. For individuals ≥21 years of age with an untreated primary LDL-C ≥190 mg/dL, after the maximum intensity of
statin therapy has been achieved, addition of a nonstatin drug may be considered to further lower LDL-C. Evaluate
the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and consider patient
preferences. (IIb C)
4. Primary Prevention; Diabetes age 40-75 with LDL 70-189
a. Moderate-intensity statin therapy should be initiated or continued for adults 40 to 75 years of age with diabetes
mellitus. (I A)
b. High-intensity statin therapy is reasonable for adults 40 to 75 years of age with diabetes mellitus with a ≥7.5%
estimated 10-year ASCVD risk unless contraindicated. (IIa B)
c. In adults with diabetes mellitus, who are <40 or >75 years of age, it is reasonable to evaluate the potential for
ASCVD benefits and for adverse effects, for drug-drug interactions, and to consider patient preferences when
deciding to initiate, continue, or intensify statin therapy.
5. Primary Prevention; without DM, ASCVD 10 year risk > 7.5 %, 40-75 years of age, LDL 70-189
a. The Pooled Cohort Equations should be used to estimate 10-year ASCVD risk for individuals with LDL-C 70 to 189
mg/dL without clinical ASCVD to guide initiation of statin therapy for the primary prevention of ASCVD. (I B)
b. Before initiating statin therapy for the primary prevention of ASCVD in adults with LDL-C 70 - 189 mg/dL without
clinical ASCVD or diabetes it is reasonable for clinicians and patients to engage in a discussion which considers the
potential for ASCVD risk reduction benefits and for adverse effects, for drug-drug interactions, and patient
preferences for treatment. (IIa C)
c. Adults 40 to 75 years of age with LDL-C 70 to 189 mg/dL, without clinical ASCVD or diabetes and an estimated
10-year ASCVD risk ≥7.5% should be treated with moderate- to high-intensity statin therapy. (I A) ★
d. It is reasonable to offer treatment with a moderate-intensity statin to adults 40 to 75 years of age, with LDL-C 70 to
189 mg/dL, without clinical ASCVD or diabetes and an estimated 10-year ASCVD risk of 5% to <7.5%. (IIa B)
e. In adults with LDL-C <190 mg/dL who are not otherwise identified in a statin benefit group, or for whom after
quantitative risk assessment a risk-based treatment decision is uncertain, additional factors may be considered to
inform treatment decision making. In these individuals, statin therapy for primary prevention may be considered
after evaluating the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and
discussion of patient preferences. (IIb C)
 6. When in Doubt; Additional Factors
a. Statin benefit may be less clear in other groups; additional factors may be considered to inform treatment decision
making.
b. 5 to <7.5% 10-year ASCVD risk
c. Primary LDL-C ≥160 mg/dL or other evidence of genetic hyperlipidemias
d. Family history of premature ASCVD
e. High sensitivity C-reactive protein ≥2 mg/L
f. Coronary artery calcium score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity
g. Ankle-brachial index <0.9
h. Lifetime risk of ASCVD
7. Secondary Prevention ASCVD
a. Clinical ASCVD includes acute coronary syndromes, history of MI, stable or unstable angina, coronary or other
arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin.
b. High-intensity statin therapy should be initiated or continued as first-line therapy in women and men ≤75 years
of age who have clinical ASCVD, unless contraindicated. (I A) ★
c. In individuals with clinical ASCVD in whom high-intensity statin therapy would otherwise be used, when high-
intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects
are present, moderate-intensity statin should be used as the second option if tolerated. (I A)
d. In individuals with clinical ASCVD >75 years of age, it is reasonable to evaluate the potential for ASCVD risk-
reduction benefits and for adverse effects, drug-drug interactions and to consider patient preferences, when
initiating a moderate- or high-intensity statin. It is reasonable to continue statin therapy in those who are
tolerating it
8. Statin Intensity
a. High-Intensity Statin (NOT MANY CHOICES!!) ★
i. Daily dose lowers LDL-C, on average by approximately ≥50%
ii. Atorvastatin 40*-80 mg
iii. Rosuvastatin 20-(40) mg
b. Moderate-Intensity Statin
i. Daily dose lowers LDL-C, on average by approximately 30% to <50%
ii. Atorvastatin 10-(20) mg
iii. Fluvastatin 40 mg bid
iv. Fluvastatin XL 80 mg
v. Lovastatin 40 mg
vi. Pitavastatin 2-4 mg
vii. Pravastatin 40-(80) mg
viii. Rosuvastatin (5)-10 mg
ix. Simvastatin 20-40 mg**
c. Low-Intensity Statin
i. Daily dose lowers LDL-C, on average by approximately <30%
ii. Fluvastatin 20-40 mg
iii. Lovastatin 20 mg
iv. Simvastatin 10 mg
v. Pitavastatin 1 mg
vi. Pravastatin 10-20 mg

Lecture 30: Diagnosis and Management of Lipid Disorders

1. Lipoproteins
a. Carry various amounts of TG and cholesterol
b. Chylomicrons = transport vehicle for dietary fat
c. VLDL = carries endogenously produced TG + secreted by liver
d. LDL = catabolic product of VLDL + major carrier of cholesterol in plasma
 i. Oxidized LDL is present in atherosclerotic lesions and enters arterial endothelium where it facilitates
accumulation of foam cell precursors. It has multiple proatherogenic characteristics.
e. HDL = Cardioprotective, inhibits foam cell accumulation in arterial wall by efflux of cholesterols from cells
f. Note: HDL = good cholesterol; LDL = bad cholesterol

2. LDL Particles
a. LDL particles are heterogeneous in size, density, and composition
i. Phenotype pattern A – Large particle size, ≥26.3 nm in diameter (less LDL particles)
ii. Phenotype pattern B – Small particle size, <25.8 nm in diameter (smaller, more dense LDL particles)
iii. Phenotype pattern I – Intermediate particle size (mixed distribution), 25.8 to 26.3 nm in diameter
b. Small, dense LDL particles (phenotype B) are cholesterol-depleted LDL particles that are associated with
i. Increased TGs
ii. Decreased HDL-C
iii. Increased risk of CHD, presumably from the excess total LDL particles
iv. Note: don’t want to have small pattern B because its bad
3. Small, Dense LDL-C
a. May have lower cholesterol concentration as reported on a standard lipid panel, but have a large number of
circulating atherogenic LDL particles
b. Increased risk of atherogenicity due to
i. Enhanced oxidative susceptibility
ii. Reduced clearance by LDL receptors in the liver with increased LDL receptor-independent binding in the
arterial wall
iii. Endothelial dysfunction that is independent of the concentrations of other lipids
4. Apolipoproteins
a. Water-soluble (lipoproteins are insoluble in plasma)
b. Function in the regulation of lipoprotein metabolism
i. Transport and redistribution of lipids among various cells and tissues
ii. Cofactors for enzymes of lipid metabolism
iii. Through maintenance of the structure of the lipoprotein particles
c. Apo-B ★ is main apolipoprotein for chylomicrons and LDL-C → atherogenic
i. Apo-B levels indicate the number of atherogenic particles present
ii. Some groups propose that Apo-B is a superior predictor of CHD compared to non-HDL-C and LDL-C
iii. Note: Apo-B is the main atherogenic one and may be a better predictor
5. Definitions
a. Lipid disorders – Includes disorders of lipoprotein metabolism but also lipodystrophies and some lipid storage
disorders. In many clinical discussions, this term has been used to mean clinical disorders associated with abnormal
levels of total, HDL, and LDL cholesterol, as well as triglycerides
b. Lipoprotein disorder – Specifically refers to clinical disorders of the lipoproteins that carry cholesterol and
triglyceride
c. Dyslipidemia – Used for lipid values that are associated with disease or increased risk of disease and for which lipid
altering therapy might be of value
d. Hyperlipidemia – Elevation of serum total or LDL-cholesterol or triglyceride
6. Dyslipidemia
a. Total cholesterol, LDL-C, triglyceride, or lipoprotein(a) levels above the 90th percentile or HDL-C or apo A-1 levels
below the 10th percentile for the general population
b. Incidence is high – in 2000 ~25% of adults in the US had a total cholesterol > 239.4 mg/dL (90th percentile cut off)
or were taking lipid lowering medications
7. Familial Hypercholesterolemia
a. High LDL-C level from birth, a propensity to tendon xanthomata, and early onset coronary heart disease
b. Monogenic, autosomal dominant disorder caused by defects in the gene that encode for the apo B/E (LDL)
receptor
c. Results in reduced clearance of LDL particles from the circulation and an elevation in plasma LDL-C
d. Increased uptake of modified LDL (oxidized or other modifications) by the macrophage scavenger receptors,
resulting in macrophage lipid accumulation and foam cell formation
e. Can be seen with mutations in the PCSK9 gene or mutations in the gene that codes for apolipoprotein B
i. Note: new medications have been made to target these mutations
f. Homozygous vs. Heterozygous FH
i. Homozygous – rare (1 in 1,000,000 births)
1. FH is inherited with gene dosing effect -> homozygotes more adversely affected than
heterozygotes
2. More common in consanguineous families in which heterozygous FH is running
ii. Heterozygous – much more common (1 in 200-500 births in North America and Europe)
1. High LDL-C levels from birth, premature CHD, a FHx of hypercholesterolemia, and tendon
xanthomata
8. Hypertriglyceridemia
a. Disorder of elevated triglycerides
i. Normal – <150 mg/dL
ii. Borderline high – 150 to 199 mg/dL
iii. High – 200 to 499 mg/dL
iv. Very high – ≥500 mg/dL
b. Percentage of adults with triglyceride levels above:
i. 150 mg/dL – 33%
ii. 200 mg/dL – 18%
iii. 500 mg/dL – 1.7%
iv. 1000 mg/dL – 0.4%
 c. Why do we care? Elevated triglyceride levels are independently associated with increased risk of CVD events
d. Note: a lot of other things can cause this (pregnancy, obesity, medications, excessive alcohol consumption)
i. There are primary causes, but we don’t need to know
e. Treatment
i. Often induced by secondary causes, so treatment is to control those disorders
ii. Lifestyle Modifications ★
1. Mild-moderate: weight loss, reducing carbohydrates
2. Very high to severe: clearance of chylomicrons becomes very slow = higher TGs in morning =
accumulation of chylomicrons = increased risk for pancreatitis ** and other manifestations of
elevated chylomicrons
a. Restrict dietary fat to less than 25-40 g daily, including “good” fats
3. Avoid alcohol overuse → can precipitate pancreatitis **
iii. Medications
1. Goal is to prevent pancreatitis and lower CVD risk
2. Treatment for TGs > 886 to lower risk of pancreatitis
3. No strong evidence that targeting hypertriglyceridemia improves CVD outcomes
4. Fibrates – Gemfibrozil and Fenofibrate
a. Can reduce TGs by as much as 50% or more
b. Can be associated with muscle toxicity, esp when combined with statin (cholesterol
medication)
5. Nicotinic Acid – Niacin
a. Can reduce TGs by 15-25%
b. Can have harmful effects when combined with statins, so not often used (not well
tolerated)
6. Fish oil – OTC or Lovaza
a. Reduces VLDL production and can lower TGs by as much as 50% or more
b. Usually needs to be high dose (4 grams per day)
9. Risk Factors for Coronary Heart Disease
a. Modifiable Risk Factors
i. Tobacco abuse
ii. Hypertension
iii. Hyperlipidemia
1. High LDL
2. Low HDL
3. High TGs
iv. Obesity and overweight
v. Physical inactivity
vi. Stress
vii. Diet and nutrition
viii. Alcohol intake
ix. Moderate okay!
b. Non-modifiable Risk Factors
i. Age (Male > 45 yo, Female > 55 yo)
ii. Gender (male)
iii. Family history of early CHD
1. < 55 yo in a male first-degree relative or
2. < 65 yo in a female first-degree relative
iv. Race (African American, Mexican American, American Indian, native Hawaiian, Asian American)
10. Risk Factor Equivalents
a. Diabetes
b. Chronic kidney disease, stage > 3B
 c. Noncoronary atherosclerotic disease (stroke, peripheral vascular disease, carotid disease, abdominal aortic
aneurysm)
d. Metabolic syndrome
11. Metabolic Syndrome
a. Arises from insulin resistance accompanying abnormal adipose deposition and function
b. Note: if 3 of 5 of these ★ → increased risk of CHD

12. How to Check Cholesterol

a. Fasting lipid profile
i. Traditionally checking cholesterol has been done fasting (patient without anything to eat for 9-12 hours
prior to the venipuncture)
ii. Includes total cholesterol, LDL-C, HDL-C, TGs
iii. Total cholesterol can be elevated or HDL-C can be low (< 40 mg/dL) with elevated TGs
b. Non-fasting lipid profile
i. Includes total cholesterol, HDL-C
ii. Calculates non-HDL-C (total cholesterol - HDL) ★
1. Better predictor of CHD risk than LDL-C alone
13. Calculating Risk - ASCVD Risk Estimator
a. In 2013 the American Heart Association and American College of Cardiology came out with new prevention
guidelines to help determine who is at risk for Atherosclerotic Cardiovascular Disease (ASCVD)
i. Defined as coronary death or nonfatal MI, or fatal or nonfatal stroke
b. Estimates 10 year and lifetime risks for ASCVD
i. Lifetime risks for ages 20-59 yo
c. Based on data from multiple community-based populations
i. Applicable to African American and non-Hispanic white men and women aged 40-79 yo
ii. For other ethnic groups, recommend using equations for non-Hispanic whites, but this may
under/overestimate risk
d. Note: looks more at the non-HDL-C (only asks about HDL and total cholesterol levels)
i. Plugs in the information and tells if you need to be on cholesterol medication → decides who needs
treatment
14. Case:
a. Mr. Jones is a 57 yo white male presenting to your clinic to establish care. He has no past medical history and
doesn’t take any medications. He is a smoker (30 pack year history). You ordered a fasting lipid panel before he
came in.
i. BP: 123/78
ii. Total cholesterol: 204
iii. HDL-C: 42
b. Risk: 12.7% → recommends moderate to high-intensity statin
c. Risk if patient quit smoking: 7.3% → probably does not need medication
15. Who Needs Treatment? (Statin Benefit Groups)
a. Primary Prevention
i. (1) LDL-C > 190 mg/dL
 1. Should be treated with high-intensity statin
ii. (2) Diabetes and age 40-75 yo with LDL-C 70-189 mg/dL
1. Moderate-intensity statin for all adults 40-75 yo with DM ★ (almost all Diabetics should be on
statin meds)
2. High-intensity statin for all adults 40-75 yo with DM and > 7.5% estimated ASCVD risk
iii. (3) No diabetes and estimated 10 year ASCVD risk > 7.5% who are between 40-75 yo with LDL-C 70-189
mg/dL
1. Moderate- to high-intensity statin
b. (4) Secondary Prevention: Clinical ASCVD
i. Includes acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial
revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin
ii. High-intensity statin therapy should be initiated or continued as first-line therapy in women and men ≤75
years of age who have clinical ASCVD, unless contraindicated

16. Statins
a. Mainstay of treatment for dyslipidemias
b. HMG CoA reductase inhibitor
c. Works in liver to prevent formation of cholesterol
d. Most effective at lowering LDL-C, but has modest effects on lowering TGs and increasing HDL-C
e. Other benefits:
i. may also improve endothelial function
ii. have antioxidant and anti-inflammatory effects
iii. stabilize atherosclerotic plaque
 f. Statin Therapy Monitoring
i. It is hard to monitor whether or not people are benefiting from cholesterol medications
1. If on high: want to reduce by > 50% from untreated baseline
2. If on moderate: want to reduce by 30-50% from untreated baseline
17. Cholesterol Absorption Inhibitors - Ezetimibe
a. Impairs dietary and biliary cholesterol absorption at the brush border of the intestine without affecting the
absorption of triglycerides or fat soluble vitamins
b. Can be combined with statins
c. Has anti-inflammatory effect like statins
d. Lowers LDL-C by about 20%
18. PCSK-9 Inhibitors - Evolocumab and Ali-rocumab
a. Injectable monoclonal antibodies
b. Can lower LDL-C by 50-80%
c. Approved for use in patients with heterozygous familial hypercholesterolemia or clinical ASCVD who require
additional reductions in LDL-C
d. Note: criteria for these getting approved are very hard so not a lot of people on them
i. Have to prove they have had a heart attack or stroke or heterozygous familial hypercholesterolemia
19. Lifestyle Modifications
a. Diet recommendations for LDL-C lowering
i. Consume a diet that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy
products, poultry, fish, legumes, non-tropical vegetable oils and nuts; and limits intake of sweets, sugar-
sweetened beverages, and red meats
ii. Aim for a dietary pattern that achieves 5-6% of calories from saturated fat
b. Diet recommendations for blood pressure lowering
i. Consume a diet that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy
products, poultry, fish, legumes, non-tropical vegetable oils and nuts; and limits intake of sweets, sugar-
sweetened beverages, and red meats
ii. Lower sodium intake
iii. Consume no more than 2400 mg of sodium per day
iv. Note: recommendations for lowering LDL-C and BP are very similar
c. Diets for weight loss
i. Reduced calorie intake for obese or overweight individuals who would benefit from weight loss, as part of
a comprehensive lifestyle intervention
1. 1200-1500 kcal/day for women and 1500-1800 kcal/day for men.
ii. Prescribe a calorie-restricted diet for obese or overweight individuals who would benefit from weight loss,
based on the patient's preferences and health status, and preferably refer to a nutrition professional for
counseling
d. Physical activity recommendations
i. Advise adults to engage in aerobic physical activity to reduce LDL-cholesterol, non-HDL-cholesterol, and
BP
1. Frequency: 3-4 sessions a week
2. Intensity: Moderate to vigorous
 3. Duration: 40 minutes on average
ii. Physical activity recommendations for secondary prevention
1. Aerobic exercise
a. Frequency: 3-5 days/week
b. Intensity: 50-80% of exercise capacity
c. Duration: 20-60 minutes
2. Resistance exercise
a. Frequency: 2-3 days/week
b. Intensity: 10-15 repetitions/set to moderate fatigue
c. Duration: 1-3 sets of 8-10 upper and lower body exercises
e. Tobacco Cessation Recommendations
i. 5 R's for patients not ready to quit (make them tell you why smoking is bad for them)
1. Relevance—Encourage the patient to indicate why quitting is personally relevant.
2. Risks—Ask the patient to identify potential negative consequences of tobacco use.
3. Rewards—Ask the patient to identify potential benefits of stopping tobacco use.
4. Roadblocks—Ask the patient to identify barriers or impediments to quitting.
5. Repetition—The motivational intervention should be repeated every time an unmotivated
patient has an interaction with a clinician. Tobacco users who have failed in previous quit
attempts should be told that most people make repeated quit attempts before they are
successful.
ii. 5 A's for patients that are ready to quit
1. Ask—Systematically identify all tobacco users at every visit.
2. Advise—Strongly urge all smokers to quit.
3. Assess—Identify smokers willing to make a quit attempt.
4. Assist—Aid the patient in quitting (gum, patches, etc)
5. Arrange—Schedule follow-up contact.
20. Why do we care about cholesterol?
a. Note: as LDL gets higher → risk of CAD increases
i. Controlling cholesterol will decrease risk of developing CAD and coronary events
21. Challenges to Treatment
a. Medication compliance
b. Diet adherence/lifestyle changes
c. Little impact of brief physician counseling on certain patients
Lecture 31: The Cold and Blue Extremity
1. Intro
a. Cyanosis: Bluish color of skin and mucous membranes resulting from ↑ concentration of reduced (de-oxygenated)
hemoglobin.
i. When occurring in an extremity, may be physiologic or pathologic.
1. Physiologic vasoconstriction occurs in cold states, when blood is shunted to internal organs
2. Pathologic cyanosis occurs as a result of arterial blood flow obstruction
3. Pathologic cyanosis results from arterial or venous thrombosis, embolism, external
compression, or vasospasm.
2. Virchow’s Triad
a. Venous Stasis + Endothelial Damage + Hypercoagulable state → Thrombosis
b. In 1845, Virchow postulated 3 factors important in the development of thrombosis: impairment of blood flow
(stasis), vascular injury, & alterations of the blood (hypercoagulability).
3. Hemostasis
a. Remarkably complex, reflecting need for fine balance between uninterrupted blood flow and rapid, localized
response to vascular injury (clotting).
b. Hemostatic processes
i. primary (platelets, vascular wall)
 ii. secondary (plasma protein) phases.
c. Primary hemostasis requires platelet adhesion, release of platelet granules, and platelet cohesion. To adhere,
platelets become attached to exposed subendothelial collagen and von Willebrand factor (vFW★). vFW allows
platelets to stick on arterial walls despite high shear stress. Consequently arterial clots are typically composed of
platelets and little fibrin (white clots). These plugs readily dislodge & embolize to distant sites.
4. Primary Hemostasis - Platelets
a. Platelet activation and secretion is driven by intracellular signaling.
i. Phospholipases liberate arachidonic acid from membrane phospholipids.
b. Arachidonic acid is converted to various platelet activators:
c. Thromboxane is short-lived (~30sec) & promotes degranulation, platelet shape change, and clumping
d. Aspirin and ibuprofen work by inhibiting cyclooxygenase .
i. Other anti-platelet drugs work on surface receptors.
ii. Platelets are closely associated with fibrinogen, which allows the primary clot to be strengthened.
5. Secondary Hemostasis
a. Secondary hemostasis is divided into 3 processes:
i. multiple-step coagulation cascade leading to thrombin generation
ii. thrombin induced formation of a fibrin clot
iii. complex fibrinolytic mechanisms aimed at limiting clot propagation.
b. Vein injuries typically are composed mainly with fibrin mesh and red blood cells (red clots).
i. The ends of such clots are friable and may break off and travel to the lungs (pulmonary embolism).
c. Red Blood Cells trapped in a cross-linked fibrin clot – a “red clot”
6. Practical Causes of Thrombosis
a. Hypercoagulable States
i. Mutations
1. Factor V Leiden
2. Prothrombin
3. Protein C & S deficiency
4. Antithrombin III
5. Hyperhomocysteinemia
ii. Acquired
1. Anti-Phospholipid antibodies:
2. Lupus antibodies
3. Anticardiolipin
4. Hyperhomocysteinemia
iii. Iatrogenic “doctor caused”
1. Prostacycline relative to Thromboxane
2. Caused by Cox-2 inhibitors - celecoxib
7. Clot Digestion
a. Regulatory mechanisms to limit the size of the clot produced
b. Plasmin activated to digest cross-linked Fibrin clots.
c. Released products are detectable in circulation and are measured as fibrin-degradation products (FDPs) & “D-
Dimers”
i. KNOW: plasmin is the active form that removes clots by breaking up fibrin → releases FDPs
1. If you suspect a DVT….order an FDP and D-dimer ★ to tell you that there is an active clot
8. Practical Causes of Thrombosis
a. Atherosclerosis (ruptured plaque) or Acute Trauma (fractures and dislocations) → endothelial damage
9. Atherosclerosis
a. Arteries are dynamic, microenvironment responds to changes in local pressure.
b. Atherosclerosis is a leading cause of arterial disease in patients over 40
i. Risk increased with diabetes, hypertension, hypercholesterolemia, hyper-homocysteinuria, & cigarette
smoking.
 c. Sites include abdominal aorta & iliac arteries (30% of symptomatic pts) and femoral & popliteal vessels (80-90% of
patients).
d. Involvement of the distal vasculature is more common in elderly and in patients with diabetes
e. Lesions form at arterial branch points where there is turbulent flow & increased shear force on the vessel wall; also
at areas of intimal injury
f. Figures show gross and histologic sections: Note foam cells in atherosclerotic plaque covered by fibrous tissue
g. Although small dense LDL are the most atherogenic, it is because they can get into the subendothelial space and
can be oxidized, leading to their relentless uptake by macrophages
i. Note: it is the OXIDIZED LDL ★ that causes damage
h. When the endothelium is disturbed, elements under the surface are exposed leading to clot formation; the
thrombus blocks downstream flow and there is resulting ischemia and vasoconstiction
10. Practical Causes of Thrombosis
a. Prolonged Immobility: Long car rides, Hospital, Airplane → Stasis
11. Cases: Some things to Consider…
a. Always use all available information!
b. Is it acute or chronic?
c. Is it or could it become emergent
d. What’s the expected course of the disease?
e. What’s the patient want to do?
f. What counsel should you give?
12. Case #1 Presentation
a. Chief complaint:
i. George W., is a 27 year old rugby player who was hit during the game today. You witnessed the injury.
b. Joint exam includes
i. Inspection & palpation, iv. Stability testing,
ii. Range of motion v. Neurologic (sensation & reflexes)
iii. Strength vi. Vascular (pulses)

c. Knee Dislocation
i. Neurovascular status – if compromised, joint must be relocated - THIS IS AN EMERGENCY!
ii. Occult damage to popliteal artery in 20% of cases.
1. Arteriogram ★ (picks up kinks - flap of endothelium that could flop open and clog off
downstream)
iii. Pulses are NOT always reliable physical exam sign of occult trauma
iv. Intima is damaged, later folds over blocking flow & leads to obstruction
v. Note: you’re worried about the popliteal artery grinding against the tibia → endothelial damage
d. Acute Arterial Thrombosis
i. Occurs where there restriction of blood flow
1. Atherosclerotic plaque
2. Vessel trauma
ii. Symptoms & character
1. Rapid onset - minutes/hours
2. Coldness, paresthesia in the limb distal to the site of occlusion.
3. Limb is cold and often cyanotic
4. Absent pulses distal to the obstruction.
e. Embolism - Acute Arterial Obstruction
i. 4x more common than thrombus in-situ (the knee dislocation case)
ii. Heart is most common source of clot
1. Atrial fibrillation
2. Acute MI
 iii. Acute MI
1. 5% have peripheral artery emboli
2. 30% of all peripheral artery emboli
3. Risk increased with larger, transmural, and anterior wall infarction
4. Primarily platelets - lodge at artery bifurcation points
iv. Dx: Arteriogram
13. Case #2
a. W.B. is a 78 year old who complains of 6 month history of gradually increasing severity of left calf ache and cramp
like symptoms with walking, which improve with sitting and resting for several minutes
i. Note: person walking and legs get heavy and have to rest → claudication (indicates peripheral vascular
disease)
b. Past Medical History:
i. Hypercholesterolemia, hypertension.
c. Social history.
i. Carpenter
ii. Smokes 1 pack per day since he was 11.
iii. Married and has several grandchildren.
d. Peripheral Artery Disease (PAD)
i. “Intermittent Claudication” is the symptom – The story
ii. Chronic arterial insufficiency
iii. Pain, ache, cramps, numbness, or fatigue in muscles; when severe, cyanosis.
iv. Onset with exertion/improves with rest ★
v. Symptoms below the level of obstruction.
vi. Night symptoms when legs are horizontal improve with legs dependent.
vii. Clues
1. History
2. Exam signs of decreased arterial reserve
a. Hair loss on lower extremity
b. Bruits
c. Nail changes (onychogryphosis - hypertrophied thick nail)
d. Shiny, atrophic, or broken down skin
e. Pallor, cyanosis

e. Intermittent Claudication
i. Symptomatic Patients have
1. 5 year survival rate of 70%
2. 10 year survival rate of 50%
3. Most deaths are sudden or secondary to heart attack.
4. 50% have significant coronary artery disease
ii. 75% of non-diabetic patients will remain stable or improve.
iii. 5% ultimately undergo amputation.
iv. Prognosis worse in diabetics and smokers.
v. Note: diabetics and smokers get this first, we can’t fix it but can slow the progression
f. Work-up for Claudication
i. Doppler ultrasound
ii. Ankle Brachial Index (ABI)
1. An ankle systolic blood pressure is < 50% of the arm is consistent with significant ischemia.
iii. Exercise testing for functional limitations.
 iv. Angiography
1. used when planning surgical intervention
2. Shows arterial “run off”
g. Treatments for Claudication
i. (ABCDE) Protocol
1. A. Anti-platelet Medication
a. Decrease platelet activity
i. Aspirin, Clopidogrel (Plavix)
b. Increase microcirculation (**)
i. Cilostazol (Pletal), Pentoxifylline (Trental)
2. B. Control BP, use Beta Blockers (CHF, MI)
3. C. Reduce Cholesterol & Cease tobacco (vasoconstriction)
4. D. Dietary fat & hypertension,control diabetes
5. E. Exercise - Progressive & strenuous (to point of symptoms)
14. Case #3:
a. 58 year old with right calf swelling for the past 2 days. Noticed it after waking yesterday. 3 days ago she rode in a
car back from Tennessee.
i. Note: unilateral extremity swelling → always think DVT
1. Hx: Long car ride and then woke up w/leg swelling….concerned that blood clot will break and go
to lung (PE)
b. Deep Venous Thrombosis
i. Blood clots in the iliac femoral or popliteal veins.
ii. Symptoms
1. Unilateral leg edema, warmth and erythema.
2. Stagnant blood leads to cyanosis – “phlegmasia cerulea dolens”.
iii. Risk for pulmonary embolism ★
iv. Usually lower extremity
1. Upper extremity (seen in “effort thrombosis” in weight lifters)
c. Physical Exam
i. Tenderness of affected calf
ii. Pulses unaffected
iii. Usually >2cm circumference difference ★ measured 10 cm below distal pole of patella.
iv. Homan’s sign used but questionable sensitivity and specificity
d. DIagnosis
i. Doppler Ultrasound
1. Tech dependent
2. Proximal vein thrombosis the Positive predictive value (PPV) is close to 95%.
3. More difficult in the calf, sensitivity is 50-75% while specificity is 95%
a. SPIN/SNOUT
ii. MRI -
iii. Venography
1. Contrast injected into veins and xray taken
e. Treatment
i. Anticoagulation
1. Heparin or low molecular weight heparins are given initially – first 24 hours ★
2. Coumadin
a. Factors II, VII, IX, X
b. Similar to vitamin K
c. Treatment 3-6 months.
d. INR
3. Drugs interfere with lab testing…
 ii. Decompression stockings (prevents the shiny, atrophic skin with pigmentation and scarring)
1. Pressure gradient
2. Elevation
iii. DVT damages vein valves
1. Chronic venous congestion
iv. Skin atrophy & ulcerated with prolonged venous pressure.
v. Note: do pedal pump at the office!!!
15. Case #4
a. This 36 year old patient comes into your office. She has had pain with exertion in the back of her calf for the past
several months. Now her toes “turn blue and white” in the cold and she had these “black spots” on the end of her
toes that are hard and dry. She smokes…
b. Physical Exam Findings
i. Triad of claudication, migratory superficial vein thrombophlebitis, and Raynaud’s phenomenon.
ii. Distal claudication
1. Trophic nail changes, skin breakdown and gangrene.
iii. Normal popliteal and brachial arteries but reduced or absent radial, ulnar, and/or tibial pulses.
c. Thromboangiitis obliterans (Buerger’s Disease)
i. Inflammatory occlusive vascular disorder of small and medium sized arteries in the distal upper and lower
extremities.
1. Not associated with proximal atherosclerosis.
ii. Incidence is 12-20/100,000.
iii. Men : Women (3:1)
iv. < 40 and Asian and eastern European descent.
v. STRONGLY related to cigarette smoking.
d. Diagnosis
i. Arteriography - shows smooth tapering segmental lesions in distal vessels and collateral vessel formation.
1. classic findings of multiple small and medium sized arterial occlusions with compensatory
“corkscrew collateral” ★ vessel formation (pathognomonic)
e. Raynaud’s Phenomenon
i. Episodic digital ischemia.
ii. After cold exposure, patient has sequential blanching, cyanosis, and rubor.
iii. Cold sensation and parasthesia often present.
iv. Women : Men (5:1).
v. Strong association with chronic vibration exposure (chainsaws, typists, jackhammers, pianists)
16. Case #5
a. A 22 year-old complains of a 3 week history of numbness in her right arm. Came on after lifting boxes moving into
her appartment. Symptoms come on quickly whenever she’s in this position. The arm never changes color. if she
rests and changes position, it gets better in a minute or two.
b. Thoracic Outlet Syndrome
i. Compression of the subclavian vessels and brachial plexus at the superior aperture of the chest, most
commonly against the first rib ★ → treat the 1st rib dysfunction!!
ii. Other terms for TOS include: scalenus anticus syndrome, costoclavicular syndrome, hyperabduction
syndrome, cervical rib syndrome, & first thoracic rib syndrome.
iii. Most common symptoms of TOS are:
1. Neck, shoulder, arm and hand pain
2. Poor circulation to the extremities
3. Weakness, numbness and fatigue in the arm and hand
iv. Thoracic outlet bounded by the scalene triangle and the clavicle & first rib
c. Clinical Diagnosis
i. Adson’s test:
 1. (+) ↓ radial pulse with arm abducted & externally rotated, while the patient looks toward
affected side
ii. EAST – Elevated arm stress test
iii. Pain at 1st rib
iv. Trunk rotation asymmetry
v. Arteriogram & EMG
d. Paget Schroetter Syndrome
i. AKA effort thrombosis
ii. Unilateral swelling of upper extremity
iii. Thrombosis of Axilosubclavian vein
iv. Associated with weight lifting & often with dysfunctions of 1st rib → pinches subclavian → clot
v. Treatment is surgical resection of first rib & anticoagulation
e. Osteopathic Treatment
i. Classical treatments
1. Strapping, Physical therapy, First rib resection
ii. Muscle Energy and HVLA
17. Summary:
a. Using all available information facilitated by
i. Knowledge of underlying disease
ii. Thorough history
iii. Directed physical examination
b. What causes a cold and/or blue extremity?
i. Secondary to arterial compromise
Secondary to venous blockage

Lecture 32: Vasculitis

1. Reminder!
a. In 2012 the big Rheum group (ACR) changed the names of
b. Churg-Strauss → eosinophilic granulomatosis with polyangiitis (EGPA)
c. Wegener’s → granulomatosis with polyangiitis (GPA)
2. Vasculitis Definition
a. Inflammation within blood vessel walls leads to vessel narrowing, occlusion, aneurysm, or rupture
b. Categorized by vessel size
i. Large, medium and small vessel vasculitides
c. Epidemiology varies among diseases
i. Age, ethnicity, and race all differ
ii. Uncommon but not rare
d. Significant overlap between disease entities
i. Presentation can range from life threatening multisystem organ dysfunction to localized skin rash
e. Etiology generally unknown
i. Can be primary or secondary disease
ii. Secondary to due to medications or autoimmune diseases
3. Categorization for Primary Based on Vessel Size
a. Large vessels – aorta & its main branches
b. Medium vessels – muscular arteries and arterioles
c. Small vessels - incorporates all vessels below macroscopic disease, includes capillaries & postcapillary venules
4. Symptoms by Vessel Size

a. Purpura - non-blanching rash when you press on it

5. H&P
a. History: Thorough including ROS (pt may not correlate rash w/elbow pain), medications, risk factors for Hepatitis
b. PE: extent of vascular lesions, the distribution of affected organs, and the presence of additional disease processes.
Look for mononeuritis multiplex and palpable purpura
c. Labs: CMP, CK, ESR, Hepatitis panel, UA, CXR, EKG
i. ANA – positive suggestive autoimmune disease
ii. Complement – can be low in cryoglobulinemia
iii. ANCA – suggestive of ANCA-associated vasculitis
6. Diagnosis and Treatment
a. Dx: generally confirmed by tissue biopsy of affected organ
b. Tx: STEROIDS are the mainstay of treatment.
i. Often require lengthy courses
ii. Can lead to multiple complications long term
iii. Some vasculitis require steroids & cytotoxic drugs such as cyclophosphamide
iv. After initial disease, move to remission and attempt to move away from steroids
c. Prognosis: Serious & sometimes fatal disease.
d. Early deaths due to active disease
e. Late deaths due to complications of therapy/disease
7. Predominantly Large Vessel
a. Aorta & its main branches are affected
b. Giant cell arteritis
c. Takayasu's arteritis
d. Behçet's syndrome – FYI (Remember Block 2?)

8. Giant Cell Arteritis ★

a. AKA temporal arteritis
 b. Pathophys: Affects large caliber vessels containing internal elastic membranes and vasa vasorum
i. Found in the extracranial arteries of the head and neck
ii. Transmural lymphocytic infiltrate in the vessel wall with disruption of the internal elastic lamina
iii. Multinucleated giant cells within vessel wall
iv. Activation of dendritic cells express TLR, activating release of cytokines → activate CD4+ → IFN-γ causes
macrophages to aggregate and granulomas to form
c. Epi: > 50 years old, women (2:1), Scandinavian descent. Most common form of vasculitis in adults. (Mean age of
onset = 79 yo)
d. Bonus: Why are intracranial arteries not affected by GCA?
i. Because these arteries lose the internal elastic lamina and vasa vasorum when the penetrate the dura
e. Distribution: Superficial Temporal Arteries, Vertebral arteries, ophthalmic & posterior ciliary arteries also
i. Note: b/c it affects the opthalmic a → worry about vision
f. S/sx: Usually begins insidiously over weeks to months
i. Constitutional symptoms: fever, fatigue
ii. New HA - temporal or occipital headache, scalp tenderness
iii. Vision loss (from inflammation of ophthalmic artery)
iv. Jaw claudication – pain in masseter muscle associated w/ chewing
v. Polymyalgia rheumatica (limb-girdle weakness) – high association
g. PE: Tenderness and thickness over involved temporal arteries, possibly bruits in neck, may see beading or pulseless
temporal a.
h. Labs: elevated CRP or ESR, normochromic anemia, thrombocytosis (increased platelets)
i. Dx: Temporal artery biopsy (see internal elastic lamina disruption on biopsy
i. Biopsy reveals a necrotizing arteritis with a predominance of mononuclear cells or a granulomatous
process with multinucleated giant cells
ii. Possibly may use clinical features alone for dx
j. Tx: Responds rapidly to corticosteroids.
i. Tx prior to Dx to avoid visual loss (will not affect biopsy results for 4 weeks).
ii. Then slowly taper steroids after 6 weeks of treatment (some need steroids > 1 year).
iii. If repeated flares, may utilize corticosteroid-sparing immunosuppressive agents such as MTX,
mycophenolate mofetil (Cellcept).
k. Complications: Aortic aneurysm, vision loss - permanent, corticosteroid side effects
9. Takayasu’s Arteritis
a. Rare, nondescript. Takes a long time to diagnose. Called “pulseless” disease.
b. Vasculitis that affects the aorta and major branches
c. Epi: Primarily young women (<40 yo), particularly Asian & Mexican
d. Pathophys: Similar to GCA. Autoimmune process targeting large elastic-containing vessels. Panarteritis involving
infiltration of DCs. Giant cells and granulomatous inflammation found in the media of the vessel.
e. Most common arteries affected: Aorta, L SC artery causing stenosis, occlusion, dilatation or aneurysm of the artery.
f. S/Sx: fatigue, wt loss, F, arthralgias/myalgias, HTN, bruits, diminished pulses, unequal arm blood pressures, aortic
regurgitation
g. Lab: elevated ESR, mild anemia
h. Imaging: Thickening of the vessel wall from inflammation can be seen on MRI, U/s & CT. MRA or angiography
also utilized.
i. Dx: Usually based on imaging and clinical presentation
j. Tx: Steroids x 1-3 months, then taper
k. Complications: stenotic vessels may require bypass, angioplasty if no collaterals present
10. Predominantly Medium Vessel Vasculitides
a. Polyarteritis nodosa (PAN)
b. Kawasaki disease
c. Buerger's disease – see Dr. Bolin’s cold & blue extremities lecture (also called thromboangitis obliterans)
d. Rheumatoid vasculitis - FYI
 e. Primary angiitis of the central nervous system - FYI
11. Polyarteritis Nodosa
a. Not ANCA associated.
b. Etiology: idiopathic, Hep B, Hep C, or hairy cell leukemia
c. Pathophys: immune complexes → transmural inflammation of muscular arteries .
i. Thickening of the vessel wall and intimal proliferation luminal narrowing, ↓ blood flow & predisposing to
thrombosis
ii. No granulomas
d. S/sx:
i. Systemic: fatigue, wt loss, muscle weakness (↑ CK), fever, arthralgias
ii. Skin - erythematous nodules, palpable purpura, livedo reticularis, digital and limb ischemia ulcers, and
bullous or vesicular eruption
iii. Kidney - renal insufficiency and HTN
iv. Neuro - mononeuropathy multiplex
v. GI – mesenteric ischemia due to ischemia in GI arteries
vi. CV - myocardial ischemia ischemic cardiomyopathy
vii. Usually spares lungs
e. Dx: Hx + PE + Biopsy of affected organ
i. Labs: Hepatitis panel, ESR, LFTs, ANCA (should be negative)
f. Tx:
i. Associated w/ Hep B or C, tx underlying infection.
ii. Not associated w/ Hep steroids & immunosuppressive medications.
g. Prognosis – poor if untreated. Renal failure and mesenteric, cardiac, or cerebral infarction are the major causes of
death.

12. Kawasaki’s Disease

a. Typically a self-limited condition. Most common vasculitis in kids.
b. Etiology: unknown. Possibly infection in predisposed pts.
c. Epi: More in Asians. Winter-spring predominance of cases is characteristic.
d. <5 yo. Male > Female
e. Medium-sized arteries, specifically coronary arteries affected.
f. Pathophysiology of Kawasaki – Proposed
Inflammatory/infectious stimulus w/ some possible genetic susceptibility → cytokines, IL, MMP target endothelial
cells fragments internal elastic lamina → vascular damage (aneurysm of coronary arteries) fibrous tissue develops
→ stenosis of vessel walls
g. Reflect widespread inflammation of medium- and small-sized blood vessels.
h. S/sx: (Dx based on 4 of the following 5 + fever > 5 days)
i. Fever – minimally responsive to antipyretics, above 38.5
ii. Bilateral conjunctival injection
 iii. Oral mucous membrane changes, including injected or fissured lips, injected pharynx, or strawberry
tongue
iv. Peripheral extremity changes, including erythema of palms or soles or edema of hands or feet (acute
phase), as well as periungual desquamation (convalescent phase)
v. Polymorphous rash - perineal erythema and desquamation, followed by macular, morbilliform, or
targetoid skin lesions of the trunk and extremities
vi. Cervical lymphadenopathy (at least one lymph node >1.5 cm in diameter)
vii. Other s/sx: V/D, tachycardia, gallop or muffled heart sounds, irritability,
i. Labs:
i. ESR elevated, elevated WBC and left shift
ii. Normochromic, normocytic anemia
iii. Pyuria (WBC in urine)
iv. Transaminitis (elevations in LFTs)
v. Hyponatremia → correlates to increased risk for coronary artery aneurysm
j. Early Diagnosis & Treatment is critical b/c helps prevent long-term complications
k. Complications: coronary artery aneurysm, cardiomyopathy with depressed myocardial contractility and heart
failure, myocardial infarction, arrhythmias, and peripheral arterial occlusion
l. Tx:
i. ASA + IVIG (only time you give kids with a fever ASA)
ii. Significantly reduces risk of aneurysm formation
iii. Effectiveness best established for pts treated within the first 7 to 10 days of illness (some benefit if given
later as well)
iv. Steroids have been used in pts who fail to respond
m. Persistent or recrudescent fever is the single strongest risk factor for the development of coronary artery (CA)
aneurysms
n. Case of 4 yo boy who at age 2 months had severe Kawasaki with documented coronary artery aneurysms.
Presented w/ CP at age 4 y, found to have EKG changes and aneurysm of RCA with 50% stenosis & LCA aneurysm
w/ 90% stenosis. Was planned for CABG but prior developed cardiogenic shock & ischemic cardiomyopathy and
AMI. Underwent CABG complicated by VF. Survived w/ no Neuro deficit. Current symptom free and in
elementary school.
o. KD pts may have long-term cardiovascular adverse effects, regardless of history of coronary artery involvement
p. Most uncertainty lies in pts w/ had CAA that regressed and their long-term prognosis & recommended surveillance
13. Predominantly Small Vessel Vasculitides
a. “ANCA-associated” disorders
i. Wegener's granulomatosis (GPA)
ii. Microscopic polyangiitis (MPA)
iii. Churg-Strauss syndrome (EGPA)
14. Whats ANCA?
a. Anti-neutrophil cytoplasmic antibodies (ANCAs)
b. Autoantibodies that mistakenly attack neutrophils
c. The major auto-antigens
i. Proteinase-3 (PR3)
ii. Myeloperoxidase (MPO)
d. Associations
i. p-ANCA ≈ MPO
ii. c-ANCA ≈ PR3
e. Initially we tested w/ immunofluorescence
i. Diffuse or cytoplasmic ANCA (c-ANCA) is largely correlated with antibodies to PR3.
ii. Perinuclear pattern (p-ANCA) is largely correlated to MPO.
f. Now we use antigen-specific testing for PR3 & MPO
i. Check anti-MPO and anti-PR3 antibodies
15. ANCA-associated Vasculitides
a. Include GPA, microscopic polyangiitis, EGPA
b. Affects small to medium sized arteries
c. “Pauci-immune” (few immune complexes) glomerulonephritis

d. Overlapping symptoms. Vasculitis can affect almost any organ.

e. Mononeuritis multiplex – vasculitis affects the vaso nervorum → critical ischemia → defined as nerve damage in
two or more named nerves in separate parts of the body
i. S/sx: pain, paresthesia, numbness, and weakness
ii. foot-drop is the most common manifestation.
iii. Pts with tibialis anterior weakness must raise their knee on the affected side high in order to avoid
tripping over the weakened foot, leading to a “foot-slapping” gait.
f. Purpuric skin rash - nonblanchable, hemorrhagic skin lesions that result from the leakage of red blood cells into
the skin
g. Dx: Usually biopsy affected tissue
h. Prognosis: rapidly progressive & usually fatal unless treated
i. Initial: Glucocorticoids, cyclophosphamides
ii. Maintenance: move off steroids as able
iii. Remissions & relapses are common
iv. Despite advances, AAVs still have higher mortality than general population
i. Complications: ESRD, death, infections, malignancy, CV disease
16. Microscopic Polyangiitis (MPA)
a. Type of ANCA associated small vessel vasculitis
b. ** Pulmonary renal syndrome **
c. Necrotizing vasculitis, pauci-immune
d. Epi: 30-50 yo
e. S/sx: hematuria, rapidly progressive loss of kidney function, pulmonary hemorrhage ( → coughing and peeing
blood)
i. 1/3 of pts have lung involvement: cough, dyspnea, pleurisy, hemoptysis, pulmonary hemorrhage
ii. Fever, arthralgia, purpuric skin rash, mononeuritis multiplex
f. Dx: p-ANCA (MPO) and biopsy of affected organ
i. Kidney: pauci-immune focal or diffuse necrotizing glomerulonephritis (indistinguishable from GPA)
ii. Note: MPA doesn’t have granulomas like GPA.
g. Tx: Steroids & cyclophosphamide
h. Prognosis: renal failure/dysfunction is prominent and may require dialysis
i. Pathophysiology: (going in depth here, but the others are very similar)
i. Trigger (infectious or environmental) leads to a burst of cytokines
ii. Primes the neutrophils or monocytes
iii. Leads to local upregulation of adhesion molecules on endothelium
iv. Enhances expression of ANCA antigens on the cell surface.
v. Activated neutrophils or monocytes may degranulate and release reactive oxygen species (O) and
lysosomal enzymes, leading to endothelial injury and further activation of the endothelial cell surface.
 vi. Products released from degranulated inflammatory cells become bound to endothelial cells and further
serve as targets of ANCA

17. Granulomatosis with Polyangiitis (GPA)

a. Formerly called Wegener’s granulomatosis
b. Organs affected: lungs, kidneys, upper airway
c. Epi: 60-70 yo, men/female equal, rare disease.
d. Systemic necrotizing vasculitis
e. Pathophys: essentially same as MPA (previous slide)
f. S/sx:
i. Constitutional s/sx: fever, migratory arthralgias, malaise, anorexia, wt loss
ii. ★ Upper airway: sinusitis, nasal/inner ear/laryngotracheal inflammation, cartilage erosion, nasal septal
perforation, saddle nose deformity, hearing loss
iii. Ocular: scleritis, uveitis, keratitis
iv. Pulmonary: cough, hemoptysis, pleurisy, cavitary multifocal infiltrates or nodules, pulmonary
hemorrhage (shows as diffuse opacities)
v. Kidney: hematuria, (often not present initially, but develops in 80% of pts over two years from
presentation)
g. Dx: Kidney or lung biopsy
i. Pauci-immune glomerulonephritis
ii. 70-80% will have +PR3 (c-ANCA)* (remember: don’t want a C on your GPA)
h. Imaging: CXR findings are variable. Common manifestations include nodules, patchy or diffuse opacities and
fleeting pulmonary infiltrates, and hilar adenopathy
i. Tx: High dose steroids, cyclophosphamide. Pt have frequent relapses
j. Prognosis: Untreated patients have a 90% mortality rate w/i 2 years.
i. Mortality rates 13% at 8 years in patients treated with cyclophosphamide.
18. Eosinophilic Granulomatosis with Polyangiitis (EGPA)
a. Formerly called Churg-Strauss syndrome
b. Characterized by Rhinosinusitis/Asthma & eosinophilia ★
c. Epi: mean 40 yo, no gender or race prevalence
d. Pathophys: eosinophilic infiltration, prominent necrosis, interstitial and necrotizing perivascular granulomas
e. S/sx:
i. Prodromal phase: atopic disease, asthma, allergic rhinitis, recurrent sinusitis (nondestructive), nasal
polyposis
ii. Eosinophilic phase: peripheral blood eosinophilia > 10%, eosinophilic infiltrates (lungs & GI tract)
iii. Vasculitis phase: vascular & extravascular granulomatosis, nonspecific constitutional s/sx,
1. Lung: migratory pulmonary infiltrates and granulomas
2. Kidney: Necrotizing pauci-immune glomerulonephritis
3. Other: purpuric skin rash, mononeuritis multiplex, heart failure,
f. Dx: Biopsy with eosinophilic tissue infiltration, p-ANCA in 40% of pts
 g. Tx: steroids & cyclophosphamide

19. Causes of Secondary Vasculitis

a. Infections - Hep C, Hep B, HIV, parvovirus B19
b. Neoplasms – Hairy Cell Leukemia
c. Autoimmune d/o – SLE, RA, Sjögren, Systemic sclerosis, IBD
d. Meds – antimicrobial, anti-thyroid, anticonvulsant, antiarrhythmic, diuretics, anticoagulants, NSAIDs, leukotriene
inhibitors, allopurinol, TNF modulators, interferon alpha
20. Buzzword Summary:
a. Large
i. GCA – Elderly, temporal artery, elevated ESR, associated w/ PMR
ii. Takayasu – Asian, pulseless disease
b. Medium
i. PAN – associated w/ Hep B, renal vessels, immune complexes
ii. Kawasaki - < 5 yo, strawberry tongue, fever and coronary artery involvement
c. Small
i. GPA (Wegener’s) – c-ANCA (PR3), Destructive URT, blood in lungs & kidneys
ii. MPA – p-ANCA(MPO), lungs and kidneys but no Nose
iii. EGPA (Churg) – asthma, sinusitis (nondestructive), eosinophilia, kidneys

Lecture 33: Congenital Heart Disease

1. Embryology
2. Fetal Circulation
a. Baby’s PaO2 is 65% at first and then raises to 95% after 10 minutes of life
b. Oxygenated blood → RA → LA → pumped out to body

c. Oxygenated blood from placenta → umbilical Vein → Ductus Venosus → Inferior Vena Cava where it mixes with
deoxygenated blood from the body → Right Atrium → Foramen Ovale → Left Atrium → Left Ventricle Aorta →
Body → Umbilical Arteries → Placenta.
d. A small amount of blood Right Atrium → Right Ventricle → Pulmonary Artery → Ductus Arteriosus → Aorta
3. Physiologic Changes in the first 24 hours after Birth
a. First Breath causes increased alveolar O2 causes vasodilation of the pulmonary vessels and therefore decreased
pressure.
b. The Ductus Arteriosus constricts and becomes the Ligamentum Arteriosus.
c. Left Atrial pressure increases and Right Atrial pressure decreases. This pressure causes the Foramen Ovale to close
and become the Fossa Ovalis.
d. The Ductus Venosus closes becoming the Ligamentum Venosum
e. Umbilical vein becomes ligamentum teres.
f. Umbilical arteries become medial umbilical ligaments
g. Note: know the structures and what ligament they become ★
4. Risk Factors
a. Family History
b. Maternal medications (NSAIDS, Lithium, Thalidomide, Hydantoin)
c. Maternal Alcohol and Cocaine use
d. Maternal Diabetes
e. Maternal infections (Rubella, Toxoplasmosis)
f. Genetic syndromes: (Down Syndrome, DiGeorge, Turner Syndrome, Noonans, William syndrome)
g. Note: structural defects can cause murmurs, but some are innocent so know how to tell the difference
5. Genetic Syndromes with Cardiac Associations
a. Note: boards love these and put the genetic disorder → want to know what congenital heart disorder
i. Pick VSD if you don’t know because it is the most common

6. Classification

7. Clinical Presentation of Heart Disease

a. Cyanosis
b. Sweating
c. Pale and Cool Skin
d. Fatigue
e. Tachypnea
f. Tachycardia
g. Weak or absent pulses
h. Poor feeding
i. Poor weight gain (should be gaining 30 grams per day for 30 days)
j. Diaphoresis (diaphoretic during feeding)
k. Fatigue
l. Clubbing (usually in 3rd world countries)
m. Edema (pitting edema)
n. Syncope
o. Heart Failure – Peripheral and Pulmonary Edema, Shock, Hepatomegaly
8. Normal Heart
 a. Understand normal heart and its flow

9. Acyanotic Heart Defects

a. Patent Ductus Arteriosus
b. Atrial Septal Defect
c. Ventricular Septal Defect
d. Coarctation of the Aorta
e. Endocardial Cushion Defect
10. Case:
a. You are called to the nursery to evaluate a baby who is 48 hours old and tachypneic.
i. Note: normal RR is 50 , want to know maternal PMHx, UDS, immunizations/prenatal care, AGPAR
b. This is a 36 weeker born via C-section due to failure to progress. Mom had good prenatal care. Mom does have a
history of gestational DM. No other medications, tobacco or alcohol exposure. All Serologies are negative.
11. What are some important components of the Physical exam that are important?
a. Vitals:
i. Height, Weight, Head Circumference
ii. Resp rate, HR, BP in all 4 extremities (assess if flow is the same throughout)
iii. Pre and Post Ductal Sats
1. Pre is before ductus arteriosus (right hand) and anything after that is post ductal
2. Should be > 95% and no more than a difference of 3
iv. Pulse Pressure: Systolic minus Diastolic
1. Normal 30-50 mm Hg
b. General:
i. Dysmorphic features, SGA, Nutritional status
c. Resp:
i. Respiratory distress, grunting, Increased work of breathing, Cyanosis
d. Cardiac
i. Murmur, thrills, displaced PMI, bounding or weak pulses
e. MSK:
i. Edema
12. Pre and Post Ductal Saturations

13. Case
a. Vital Signs: T 98.9F RR 80 HR 180 BP 130/90 O2 Sat 97% On RA
i. Note: important to ask if saturation is on room air or on supplemental O2
b. Gen: In apparent respiratory distress, Fussy
c. HEENT: NCAT PERL Oropharynx and nares without obstruction or lesion
 d. RESP: Tachypneic, Nasal flaring, Subcostal and Intercostal Retractions
e. CV: Tachycardia Harsh systolic ejection murmur heard left Axilla and Back.
f. Abd: Soft/ND/NT, no hepatosplenomegaly noted
g. EXT: No clubbing cyanosis or edema Right Brachial pulses easily palpated but right femoral pulse seems weak.
i. Note: femoral pulses weak = coarctation
h. Derm: No rashes. Capillary refill in the right hand is brisk but in the left foot very prolonged.
i. You ask the nurse to take 4 extremity BP’s and sats.

14. Patent Ductus Arteriosus (PDA)

a. 5-10% of congenital heart disease
b. The ductus typically closes in 24 to 48 hours of life.
c. PDA is due to failed closure of the ductus
d. If the ductus fails to close, as the pulmonary pressure drops blood is
allowed to flow from the Aorta to the Pulmonary artery causing a left
to right shunt.
e. Increased incidence noted in premature and maternal Rubella.
f. Clinical Presentation:
i. Severity of symptoms depends on the extent of shunting
ii. The amount blood being shunted depends on the size of the PDA
iii. PE
1. Murmur: Continuous Machine like murmur ★ heard best on the 2nd left intercoastal space
2. Widened Pulse pressure
3. Bounding Pulse
4. Thrill and / or Displaced PMI if severe
g. Diagnosis and Treatment
i. If PDA is small, the imaging and EKG might be normal
ii. EKG:
1. Right ventricular hypertrophy due to increase pulmonary HTN
2. Note: EKG will show right axis deviation
iii. CXR:
1. Increased pulmonary vasculature
2. Enlarged pulmonary arteries
iv. Echo: Left to right shunting
v. Treatment:
1. Supportive measure
2. Closed with indomethacin/ ibuprofen
3. Surgical ligation
- Note: if patient has PDA, some are ductus dependent
lesions and need prostaglandins to keep it open
15. Atrial Septal Defect
a. Approximately 10% of all congenital heart defects
b. Atrial septum grows out of the endocardial cushions to divide the
atrium.
c. Failed growth or excessive resorption of the septum causes ASD.
d. Higher pressures in the left atrium causes a left to right shunt
e. Increased incidence in Down syndrome and Fetal Alcohol syndrome.
f. Clinical Presentation
 i. Asymptomatic
ii. Respiratory distress
iii. Failure to thrive
iv. Exercise intolerance
v. Large ASD’s can cause pulmonary edema and right sided heart failure
1. there’s more blood left to right → right atrium to right ventricle → right has to work harder to
pump out
vi. Systolic ejection murmur. Fixed split S2
1. Note: hear two sounds (pulmonic valve closes after aortic valve)
g. EKG:
i. Right axis Deviation (right heart is working harder)
ii. Right ventricular enlargement

h. CXR: Cardiomegaly
i. Echo: Showing left to right blood flow across ASD
j. Treatment:
i. If small: monitoring
ii. Gold standard is surgical closure
16. Ventricular Septal Defect
a. Most common of all Congenital Heart defects ★
b. Caused by a defect in formation of the ventricular septum
- Membranous portion or muscular portion
c. Left to right shunt
d. Increased incidence in Downs Syndrome, FAS and gestational DM.
e. Clinical Presentation
- Typically asymptomatic at birth
- Around 6-8 weeks of life pulmonary vascular resistance decreases
which increases the left to right shunt causing symptoms.
- Small VSD’s often have a loud murmur (smaller hole, louder the
murmur)
- Pansystolic murmur heard best at the left lower sternal base.
f. Diagnosis and Treatment
i. EKG:
1. Small VSD will have a normal study
2. Large VSD shows left ventricular hypertrophy
a. Note: this is because the aorta doesn’t have enough blood and tells body to pump
harder → tachycardia and hypertrophy, but makes shunting worse
ii. CXR: Cardiomegaly and increased pulmonary vasculature
iii. Echo: Showing defect in the septum and left to right shunt
iv. Treatment:
1. 1/3rd will close spontaneously
2. Initial Tx: Diuretics, digoxin for afterload reduction
3. Surgical Closure
17. Endocardial Cushion Defects or Atrioventricular Canal Defect
a. Caused by abnormal development of endocardial cushion which causes failure of the
septum to fuse with the endocardial cushion leading to abnormal atrioventricular
valves.
b. Defect may be partial or complete
- Complete: Only one common AV valve
- Partial: Two AV valves but one might be malformed.
c. Left to right shunting through the ASD and VSD
 d. Could lead to atrioventricular valve insufficiency
e. Increased incidence in Down’s Syndrome.
f. Clinical Presentation
- Typically develop around 6-8 weeks when the pulmonary vascular resistance decreases leading to left to
right shunt
- Symptoms vary based on the defect and if there is AV valve insufficiency
- Pulmonary valve hypertension may develop
- Variable murmur
g. Diagnosis and Treatment
i. ECG: Left axis deviation
ii. CXR: Cardiomegaly with increased vascular markings
iii. Echo: Blood flow through the defect
iv. Treatment: Diuretics and Surgical repair
18. Coarctation of the Aorta
a. 8 to 11% of CHD; Boys > Girls
b. Congenital narrowing of the Aorta
c. Can have associated anomalies
d. If there is a severe coarctation, then it will be ductal dependent.
i. Note: have an ↑ likelihood of increasing oxygenation if you decrease the circuit (keep heart from not
working hard)
e. Increased incidence in Turner Syndrome
f. Clinical Presentation
i. Failure to thrive
ii. Leg pain with exercise
iii. Respiratory distress
iv. Headache
v. Harsh Systolic ejection murmur heard best in the left axilla and back.
vi. Weak or absent femoral pulses
vii. Upper extremity hypertension
g. Diagnosis and Treatment
i. ECG: Left Ventricular hypertrophy
ii. CXR: Rib notching is a late finding
iii. Echo: Location and degree of coarctation
iv. Treatment:
1. Initially Prostaglandins and diuretics
2. Cardiac catheter and Ballooning
3. Open heart surgery

Lecture 34: Congenital Heart Defects - Cyanotic

1. What is Cyanosis
a. Central
i. Typically caused by cardiac or respiratory issues
ii. Involves the trunk and mucous membranes
b. Peripheral
i. Located on the hands and feet (acrocyanosis)
ii. Sluggish blood flow in capillaries due to cold or peripheral vascular disorder
iii. Does not include trunk or mucous membranes.
2. Clinical Presentation of Heart Disease
a. Cyanosis, Sweating, Pale and Cool Skin, Fatigue, Tachypnea,
Tachycardia, Weak or absent pulses, Poor feeding, Poor weight
gain, Diaphoresis, Fatigue, Clubbing, Edema, Syncope, Heart
Failure – Peripheral and Pulmonary Edema, Shock, Hepatomegaly
3. Truncus Arteriosus
a. 1% of congenital Heart defects
b. Causes by the failure of the Truncus to divide into the Aorta and
the Pulmonary arteries → Leads to one great vessel with a single
valve → Pulmonary Hypertension
c. Large VSD

d. Clinical Presentation
i. Cyanosis is minimal
ii. Will hear a continuous systolic ejection murmur that radiates to the back with a single loud S2.
iii. Bounding pulses (a lot of blood going through both vessels into the truncus)
iv. Infants will develop congestive heart failure, tachypnea and cough in the first couple of weeks
1. Note: seem uncomfortable when they are eating (sweating and uncomfortable)
e. Diagnosis and Treatment
i. CXR: Large heart with increased pulmonary vascular markings
ii. ECG: Bilateral ventricular hypertrophy and cardiomegaly
1. Note: right side is pumping harder because pulmonary resistance is higher
iii. Echo: Shows with single outflow
iv. Treatment:
1. Diuretics for CHF
2. Surgical corrections in the first few weeks of like
a. Close the VSD
 b. Separate the pulmonary artery from the trunk
c. Make a connection between the right ventricle and pulmonary artery.
3. Fatal by 1 year if untreated.
4. Transposition of the Great Vessels

a. 5% of all congenital heart defects

b. Most common cyanotic heart disease to present in a newborn
c. Defect:
i. The Aorta that should arise from the left ventricle and carry oxygenated blood to the rest of the body now
arises from the right ventricle and carries deoxygenated blood to the body
ii. The Pulmonary artery that should arise from the right ventricle and carry deoxygenated blood to the lungs
now arises from the left ventricle and carries oxygenated blood to the lungs.
d. Survival depends on having a mixing lesion.
i. PDA, ASD, PFO, VSD
e. Ductal Dependent lesion
f. Clinical Presentation
i. As the ductus closes the neonate will be cyanotic
ii. No murmur
iii. Tachypnea
iv. Clubbing
v. And all the other signs and symptoms of heart defects
g. Diagnosis and Treatment
i. CXR:
1. Egg on a string appearance
2. Increased pulmonary vasculature
ii. EKG:
1. RVH
2. R axis deviation
iii. Echo:
1. Diagnosis to define the flow
iv. Treatment:
1. Prostaglandin E1 to keep the ductus arteriosus open.
2. For those who do not respond to the PGE1 undergo the Rashkind procedure.
3. Surgery is done within the first week.
4. Procedure of choice is the arterial switch
5. Good long term outcome.
5. Prostaglandins E1 (PGE1)
a. Alprostadil
 b. It is a derivative of an endogenous substance that keeps
the ductus open in utero.
c. Administration prevents the ductus from closing.
d. The drip should be started before the ductus closes
e. Side effects:
- Apnea, flushing, hypotension, seizure, fever
- Be prepared to intubate
6. Tetralogy of Fallot
a. 9-14 % of all congenital Heart defects
b. Most common cyanotic heart defect
c. 4 components:
- Pulmonary stenosis
- RV hypertrophy
- Large VSD
- Overriding Aorta
d. Clinical Presentation
i. Cyanosis within the first year of life
ii. Tet spells
1. Sudden development of blue skin, nails and crying due to transient increase pulmonary
resistance
2. Rapid drop in amount of oxygen in the blood.
3. The instinctive squatting maneuver increased blood to the lungs
iii. High pitched systolic ejection murmur
iv. Signs and symptoms of heart defects
e. Diagnosis and Treatment
i. CXR:
1. Boot shaped heart
2. Decreased pulmonary vasculature
ii. EKG: RVH
iii. Echo:
1. Can see the 4 components
2. Prenatal echo
iv. Treatment:
1. PGE1 if severe pulmonic stenosis is noted
2. Beta blockers used while waiting for surgery
3. Staged surgery
4. Might need an artificial pulmonic valve
5. If untreated can lead to Right heart failure
7. Tricuspid Atresia
a. 2% of all CHD
b. Endocardial cushions fail to form the valve
c. Defect:
- Complete absence of the tricuspid valve
- Hypoplastic Right ventricle
- An ASD or PFO and VSD or PDA are required for mixing and survival.

d. Clinical Presentation
i. Cyanosis unresponsive to Oxygen
ii. Single S2 with a holosystolic murmur
iii. Tachypnea
 iv. Similar signs and symptoms for heart defects
e. Diagnosis and Treatment
i. CXR:
1. Variable heart size
2. Decreased pulmonary vascular markings
ii. ECG:
1. LVH
2. LAD
iii. Echo:
1. Diagnosis
iv. Treatment:
1. PGE1: ductal dependent for pulmonary circulation if no or small VSD
2. Surgery is palliative and not curative
3. Goal of surgery is to get blood to the lungs
4. Post op patients can develop arrhythmias,
effusions, CHF
8. Total Anomalous Pulmonary Venous Return (TAPVR)
a. Approximately 1% of CHD
b. Defect:
- The pulmonary veins are malpositioned.
- Therefore they bring oxygenated blood into the right
heart rather than the left.
- PFO or ASD essential for survival
c. Types:
- Supracardiac
- Infracardiac
- Cardiac
- Mixed
d. Clinical Manifestations
i. Cyanosis severity is dependent on amount of obstruction of drainage from pulmonary veins
ii. Poor growth
iii. Tachypnea
iv. Dyspnea
v. Other signs and symptoms of CHD
e. Diagnosis and Treatment
- CXR:
1. Snowman sign
2. Cardiomegaly
- ECG:
3. RAD
4. RVH
- Echo:
5. Diagnostic
- Treatment:
6. PGE1 ???
7. Surgical correction in the first month of life
8. Prognosis is good
9. 80% will die if not corrected by 1 year of age
9. Double Outlet Right Ventricle
a. 1% of CDH
b. Defect:
- Both great vessels connect to the right ventricle
- A VSD is always present
c. Symptoms:
- Cyanosis
- Tet Spells
- Holosystolic murmur and a diastolic rumble
d. ECG:
- RVH since pushing against systemic pressures of the aorta
- Atrial enlargement
e. CXR: Cardiomegaly
f. Echo: Diagnosis
g. Treatment:
i. Diuretics and ACE inhibitors for Right sided heart failure
ii. Surgical correction
iii. Prognosis depends on the size and location of the VSD or any other defects
10. Hypoplastic Left Heart
a. 1-2% of CHD
b. Most common cardiac defect to cause death in the first month of life
c. Most complex and most challenging
d. Boys > girls
e. Defect:
- Hypoplastic left heart
- Stenotic or no mitral valve
- Small aorta and small or stenotic aortic valve
- ASD or PDA (2 connections necessary for survival)
f. Clinical Presentation
i. Cyanosis develops as the ductus closes
ii. 1/3rd of infant will present in shock
iii. Soft systolic ejection murmur
iv. Single loud S2.
g. Diagnosis and Treatment
i. ECG:
1. Sinus Tachycardia
2. RA enlargement
3. Right ventricular hypertrophy
4. Right Axis deviation
ii. CXR:
1. Cardiomegaly
2. Increase pulmonary vascular markings
iii. Echo: Diagnostic
iv. Treatment:
1. Do not give oxygen
2. PGE1 ductal dependent
3. Surgical treatment in stages
4. Untreated will lead to death in 1-2 weeks of life
11. Ebstein’s Anomaly
 a. Less than 1% of CDH
b. Associated with maternal lithium use
c. Defect:
- Downward displacement of the tricuspid valve into the right ventricle
- Also has PFO or ASD

d. Clinical Manifestations
i. Depends on degree of cyanosis which depends on the extent of left to right shunt
ii. Can present at any age.
iii. Signs and symptoms of CHD
iv. Pansystolic murmur of tricuspid insufficiency heard best on the right 4rth intercostal space.
e. Diagnosis and Treatment
i. ECG: Large p waves
ii. CXR: Very large heart and decreased pulmonary vascular markings
iii. Echo: Diagnosis
iv. Treatment:
1. Timing of surgery is dependent on severity
12. Pulmonary Atresia
a. Defect: Lack of formation of the pulmonary valve
b. Types:
- Pulmonary Atresia with intact ventricular septum
1. RV does not develop due to blood flow → MPA
remains small → Pulmonary valve does not form
- Pulmonary Atresia with a ventricular septal defect
2. RV not as small in utero due to left to right shunt
via VSD → very similar to Tetralogy of fallot.
c. Clinical Manifestation
i. Severe cyanosis and increased work of breathing as soon as the PDA closes
ii. Signs and symptoms of CHD
d. ECG: Mild left axis deviation
e. Echo: Diagnostic
f. Treatment:
i. PGE1
ii. Catheterization
iii. Surgery

LECTURE 36: CHRONIC MANAGEMENT OF CORONARY ARTERY DISEASE

1. Definition: symptom complex when atherosclerotic coronary vessel supply can’t meet demand (ischemia)
2. Discomfort in chest, or back, shoulder, arm usually lasting up to 10 minutes
3. Aggravated by stress or exertion (trouble exercising) & relieved by rest or nitroglycerin
4. Women > men
5. Stable
6. Induced by physical exertion, exposure to cold, eating, emotional stress; Lasts 5-10 minutes, relieved by rest or nitroglycerin
7. EKG: Normal or nonspecific ST-T changes, Signs of previous MI (Q wave slight elevated), ST segment depression during angina
8. ≥70% luminal narrowing of one or more coronary arteries from atherosclerosis
9. Medical therapy: Aspirin, sublingual NTG, anti-ischemic medications*
10. Tx goals: 1st prevent further coronary obstruction, MI, & death, 2 nd limit sxs that interfere with exercise capacity
11. Unstable: unstable until proven otherwise!!***
12. Increase in anginal frequency, severity, or duration now occurring at less activity/rest; may be less responsive to NTG
13. EKG: Same as stable angina although changes may be more pronounced
14. Plaque rupture with platelet and fibrin thrombus causing worsening coronary obstruction
15. Medical therapy: Aspirin, anti-ischemic medications, heparin or LMWH, glycoprotein IIb/IIIa inhibitors, statin
16. Prinzmetal’s or Variant
17. Angina without provocation, typically at rest
18. EKG: Transient ST segment elevation during pain; Often with associated AV block or ventricular arrhythmias
19. Coronary artery spasm
20. Medical therapy: CCBs, nitrates (beta blockers can make it worse)
21. Office Management
22. Characterize chest pain, reduce risk factors for progression, prescribe meds, tx sxs, detect changes, prevent MI/death
23. Angina must include: Substernal chest discomfort/pressure, provoked by exertion/emotional stress, relieved by rest/NTG
24. Assess physical functioning using NYHA Classification***
i. Class I: no limitation of activity
ii. Class II: slight limitations – walking up stairs rapidly, exertion after meals
iii. Class III: marked limitation – walking 1-2 blocks, stairs at normal pace
iv. Class IV: inability to carry out physical activity at rest
25. Physical Examination look for
i. Signs of vascular disease: abnormal fundi, decreased peripheral pulses, bruits
ii. End organ damage from HTN: abnormal fundi, bruit
iii. Aortic valve stenosis: systolic murmur, abnormal pulses
iv. Let sided heart failure: S3, displaced PMI, rales
v. Right sided heart failure – JVD, ascites, edema
vi. Ear lobe dent/bulb thing – Sign of CHF
26. DDx for Anginal Pain
i. Cardiovascular non-ischemic: aortic dissection, pericarditis
ii. Pulmonary: PE, pneumothorax, pleuritic, pneumonia
iii. GI: esophageal reflux, biliary colic, cholecystitis, peptic ulcer, pancreatitis
iv. Chest wall: costochondritis, VZV, rib fracture, somatic dysfunction
v. Psychiatric: anxiety, somatoform disorder, affective disorder, thought disorder
27. CAD Risks
28. Non-modifiable: Age, male, FHx
29. Modifiable: Hyperlipidemia, HTN, DM, Metabolic syndrome, cigarettes, sedentary lifestyle, heavy ETOH, obesity
i. Smoking: complete cessation
ii. BP control: <140/90 if age < 60 or if 60+ with CKD
iii. Lipid management: if 10 year ASCVD > 7.5%, treat with statin
iv. Weight management: BMI < 25; waist circumference < 40 in for men, < 35 for women
v. Influenza & pneumococcal vaccine
30. Medications with evidence of CAD reduction
31. ASA: taken by all patients with CAD unless allergic, failed therapy or angioplasty
32. BBs: particularly in patients with previous MI – reduces HR/contractile force & blocks sympathetic tone
i. B1 selective: atenolol, metoprolol Nonselective: propranolol
ii. SE: bradycardia, impaired glucose control, depression, impotence, exercise intolerance
33. Statins: limit cholesterol synthesis & increase catabolism of LDL-C
34. ACEI: reduce cardiovascular death, M I, & stroke – reduces vasoconstriction & PVR/BP
i. SE: cough, potential worsening kidney function & hyperkalemia, angioedema
35. ARBs: block ANTII receptors, decreasing vasoconstriction & release aldosterone
36. Nitrates
i. Decrease myocardial oxygen demands by systemic vasodilation, reduce preload, dilate coronary arteries
ii. Improve exercise tolerance
iii. Increased therapeutic response when added to BBs or CCBs
iv. Cannot take with PDIs (Viagra, cealis)
37. CCBs: block Ca2+ into myocytes – coronary and peripheral arterial vasodilators
 i. Dihydropyridines: greater effect on vascular smooth muscle (Amlodipine, nifedipine)
ii. Nondihydropyridines: decreased ionotropic & chronotropic action (Verapamil, diltiazem)
38. Antiplatelets: Aspirin (COX inhibitor), Clopidogrel (inhibits ADP receptors)
39. Effectiveness of Treatment for CAD (SORT)*
40. A: consistent, good quality patient-oriented evidence
i. Aspirin – if contraindicated, consider clopidogrel
ii. Cholesterol reduction – when LDL ≤ 130 and target LDL < 100
iii. BP control – goal ≤ 130/80
iv. Coronary artery bypass grafting
41. B: inconsistent or limited-quality patient-oriented evidence
i. BBs – initial therapy in absence of contraindications
ii. ACEs: up to 17% reduction in mortality in post MI patients
iii. CCBs & long-acting nitrates – in combination with BBs or when BBs are ineffective or contraindicated
iv. Smoking cessation therapy – provide counseling, nicotine replacement, formal programs
v. Cholesterol reduction – when LDL = 100-129 and target LDL < 100
vi. Exercise program – moderate intensity activity 30 mins 3-4 times per week
vii. Percutaneous transcutaneous angioplasty – anatomy suitable for catheter treatment and normal LV function
viii. CABG or PTCA – patients who failed medical therapy
42. C: consensus, disease-oriented evidence, usual practice, expert opinion, case series
i. Sublingual NTG – immediate relief of angina
ii. Weight reduction – in patients > 120% ideal body weight
iii. DM management – data lacking
43. CATH: When dx is uncertain after NIT, determination of therapy surgical vs medical, when intervention is necessary (STEMI)
44. CABG: Extended survival in pa tients with severe left main disease or severe three vessel disease and depressed LV dysfunction
45. Courage Trial: Addition of PCI to OMT did not reduce cumulative rates of MI and death and was not cost-effective

LECTURE 37: CONGESTIVE HEART FAILURE

Cor Pulmonale – Right Ventricular Failure
 Definition: alteration in RV ventricle, independent of LV failure
 Major causes: ACUTE – Adult Respiratory Distress Syndrome & massive PE CHRONIC – COPD
 Physiologic Effects: exertional dyspnea, decreased arterial saturation due to V/Q mismatch
 Tx: NO digoxin, review instructions with pt, lifestyle modifications & smoking cessation are the two biggest problems with pts
Left Ventricular Failure
 Definition: Inability to supply enough blood to meet the metabolic needs of the human body – must compensate in the ventricle, etc.
 30-35% of pts with the most severity diet within 1 year due to hemodynamic deterioration or a malignant ventricular arrhythmia
 Causes: 1. Ischemic Heart Disease, 2. Dilated Cardiomyopathy, 3. Valvular Heart Disease
 Check out slide 9 for pathophysiology
 Systolic Dysfunction – heart failure with reduced ejection fraction (HFrEF)
o #1 cause is ischemic heart disease
o Dilation of LV = eccentric hypertrophy (myocytes in series) → low EF and CO

 Afterload dependent
 Tx: general measures (diet, exercise, etc.), ACEI/ARB, BB, Diuretics, Aldosterone antagonist
 Remember: hydralazine & isosorbide dinitrate for Af. Am.
 Indications for devices!
  ICD (Class II or III): expected survival > 1 year & either ischemic cardiomyopathy ≥ 40 days post MI OR nonischemic w/
EF ≤ 35%
 Cardiac Resync therapy (CRT) [Class II-IV]: LVEF < 35%, QRS > 120 ms, on maximal medical therapy
 Left Ventricular Assist Device: awaiting cardiac transplant or recovery from cardiogenic shock, destination therapy
(will die)
 Diastolic Dysfunction – heart failure with preserved ejection fraction (HFpEF)
 LV is stiff & can’t relax = concentric hypertrophy (myocytes in parallel)
 Preload dependent
 Tx: generally same as HFrEF but the same drugs don’t seem to work – Candesartan seems beneficial
 Evaluation: Hx, PE, Labs (CBC, CMP, UA, BNP), CXR, EKG, TEE (most important)
 BNP: B-type natriuretic peptide – raises with HF
 Normal pulmonary capillary wedge pressure = 8-12 mmHg
 Know the NYHA Classification to the right! TEST QUESTION!
 Stages of CHF: 1. Redistribution, 2. interstitial edema, 3. alveolar edema
 Signs: 1. Cardiomegaly, 2. Peribronchial cuffing, 2. Air bronchogram
 Sign of stage 2: Kerley B Lines: short, parallel lines in lung periphery, representing fluid in interlobular septa
 Mostly seen at the costophrenic angles on PA and in substernal region on lateral views
 Acute Decompensated LV Failure/Pulmonary Edema
 ABCs: stable or unstable? Keep O2 sat >90%
 Twin objectives of pharm therapy: relief of pulmonary congestion & improved systemic tissue perfusion
 Pharm Treatment: slide 37 & 38
 Furosemide doesn’t work when the BP is too high or low
 BP is too high? Give NTG
 SBP 70-100 with no S/Sx of shock? Give Dobutamine
 SBP < 70? Give NE
 Morphine isn’t used anymore for preload reduction – used for sxs control & pain
 Continue current medications, but take off BB if hemodynamically unstable
 Identifying end stage LVHF: intolerance to meds, constant SBP < 90 mmHg, 2+ hospital visits for HF, progressive Na+ decline,
etc.
 Discharge Criteria: LV function assessment, medical therapy. NOTE: Risk of re-admission and death is highest 30 days after
discharge
 FOUND ON GOOGLE (idk if it’s right): Galt became a military surgeon and served as director of the VA state apothecary until
1780.

Lecture 38: Adult Congenital Heart Disease

1. Definition - ACHD
a. Congenital cardiovascular disease – abnormality in cardiocirculatory structure or function that is present at birth,
even if it is discovered much later.
b. An estimated 85% of children diagnosed with CHD will survive into adulthood
i. Some CHD is not diagnosed in infancy and more often dx in adults when causes clinical symptoms
1. E.g. ASD, VSD, coarc
ii. Some CHD repaired/corrected kids doing well and surviving until adulthood and need management as
adults
c. The overall # adult patients with CHD is now > pediatric cases
i. 3,000 per million adult CHD patients in US in 2012
d. Not simply continuation of childhood experience. Lesions and risk factors change
i. Arrhythmias, Valve failure, CHF, lipids, HTN, rapid progression of stenotic lesion
2. Atrial Septal Defects
a. 2nd most common CHD lesion in adults
b. 4 types
i. Ostium primum
ii. Ostium secundum ← Most Common
iii. Sinus venosus
iv. Coronary sinus defects
c. Causes L → R shunt
d. Size of the shunt matters
i. Larger ASD may cause CHF and FTT in child (will present earlier in life)
 ii. Smaller ASD may not be detected until adolescent/adulthood. (will present later in life)
e. Adolescent/Adult presenting s/s:
i. Asymptomatic: only have murmur or abnormal CXR or abnormal EKG
ii. Symptomatic: Exercise intolerance, palpitations
iii. Can progress to cyanosis, right ventricular failure right axis deviation on EKG
f. !!! Wide and fixed split S2!!!! & Systolic Ejection Murmur at 2nd Left intercostal space (pulmonic area)
g. Dx: Echocardiography (ultrasound)
h. Tx: When symptomatic or clinically relevant, device closure or surgery
i. Long term: risk for atrial fibrillation
i. Because electrical impulses are generated in the right atrium

3. Ventricular Septal Defect

a. Classified by location and margins
i. Membranous, muscular (most common is perimembranous)
b. Size of defect causes type of shunt
i. Small/ min restricted L→R – usually no LV vol overload or pulm HTN
ii. Moderately restricted L→R - causes L atrial and ventricular dilation and dysfunction and ↑ in pulmonary
vascular resistance
iii. Large/nonrestricted – Lg L R shunt with vol overload → pulm HTN → can progress to Eisenmenger
c. Adult presenting s/s:
i. Small VSD– usually asysmptomatic
ii. Mod VSD – varies; asymptomatic to CHF in child (R sided overload can lead to CHF)
iii. Lg VSD – Most present w/ CHF in childhood
d. PE: Harsh pansystolic (across all of systole)/holosystolic murmur – smaller the VSD, louder the associated murmur
e. Dx: Echo
f. Tx: Patch or device closure
g. Long-term complications: residual VSD, heart block, arrhythmias, Pulmonary Artery HTN, aortic or tricuspid valve
regurgitation
4. Coarctation of the Aorta
a. Constricted aortic segment w/ some infolding of neointimal tissue
i. Classically located in the thoracic aorta distal to the origin of the L SC artery at about the level of the
ductal structure
ii. Collateral vessels/blood supply often develop
b. If obstruction is severe, will present in infancy
i. Clinical s/s: decreased pulses in LEs, CHF, hypoperfusion
c. Adult presenting s/s:
i. Weakness/pain in legs (leg claudication), difference in BP btwn/ UE & LEs, difference in BP btwn/ arms,
reduced femoral pulses (or delay), LVH, exertional headaches, possible midsystolic murmur over chest &
back (murmur radiates to the back and becomes continuous when severe)
d. Associated with
i. Turner’s syndrome (45 XO)
ii. Bicuspid aortic valve (50%)
e. Long-term: LVH, recoarctation, HTN, Early CAD, Aortic aneurysm, endocarditis
f. Coarc Dx:
i. CXR – may show rib notching
 ii. Doppler echo
iii. MRI
g. Treatment
i. Balloon dilation and/or stent placement
ii. Goal = get more blood flow around the choke point by opening the area back up
5. Fetal Circulation
a. Foramen Ovale - allows most of the blood that enters the RA to flow into the left atrium bypassing RV.
i. From LA, the oxygenated blood is pumped into LV & into the aorta, which carries it to the body tissues
ii. Bypasses the lungs since the lungs don’t oxygenate a fetus’ blood
b. Normally the foramen ovale closes at birth when increased BP on the left side of the heart forces the opening to
close.
6. Patent Foramen Ovale
a. ~25% general population has this
b. Usually asymptomatic
c. Possibility for clot to pass from R → L of heart (bypassing the lungs) and then go to brain
i. Paradoxical embolus → Cryptogenic stroke
d. 92% had R→L shunt with Valsalva
e. ↑ incidence of migraines in pts with PFO. ???? Pathophysiology & ??? Closing PFO decrease migraines
i. No clear indications for closing PFO at this time.
f. Dx: Bubble study
i. TTE with agitated saline injected. Pt Valsalva and you see the bubbles go RL across the PFO
g. ?? Close the PFO in Stroke Patients ??
i. In patients with cryptogenic stroke or TIA who had a PFO, closure with a device did not offer a greater
benefit than medical therapy alone for the prevention of recurrent stroke or TIA.
7. Congenital Aortic Stenosis
a. Patho: thickening of the valve and commonly bicuspid (also can be uni or tri). Will secondarily calcify in adulthood
leading to presentation in adulthood
b. Adult presenting s/s: Varies
i. Asymptomatic all the way to
ii. Dyspnea, angina, syncope, and ultimately heart failure (usually 50-70 yo)
c. PE: systolic ejection murmur (crescendo-decrescendo) at the “aortic area” or R 2nd intercostal space w/ radiation
to carotids
d. Dx: Echo
e. Tx: Medical therapy when early & asymptomatic. Surgery w/ valve replacement when symptomatic or severe AS.
f. Bicuspid valves may need aortic root repaired/replaced if enlarged
g. Pathophysiology:
i. Aortic stenosis → LV Hypertrophy → LV dilation → CHF
ii. The valve doesn’t allow blood out and left heart works harder causing it to become fatigued and lead to
heart failure

8. Various Surgeries for CHD

a. Device closure via catheterization
i. Used for ASD and PFO
b. VSD
i. If small, closed by device
ii. If large, may require open-heart surgery and patch
iii. Often can be seen with various other CHD lesions
c. Blalock-Taussig Shunt
 i. AKA “BT shunt” or “modified BT shunt”
ii. Often first step of the surgery for single ventricle repair
iii. Palliation - ↑ blood flow to lungs
iv. R or L Subclavian artery to Branch PA
v. Note: increase blood flow to the lungs and get more oxygen
d. Tetralogy of Fallot Repair
i. TOF defects
1. Large VSD
2. Narrowing of RVOT
3. Overriding aorta
4. RVH
ii. Sometimes staged with modified BT shunt first
iii. Then next surgery in few months:
1. Patch VSD
2. Widen outflow tract with patch
3. Remove shunt
e. Fontan
i. Used as correction for a “single ventricle” (E.g. TA, PA, HLHS, HRHS and double-inlet ventricle)
ii. Fontan procedure results in the flow of systemic venous blood to the lungs without passing through a
ventricle
iii. Staged procedure
1. Typically completed btwn 18 mo & 4 yo
f. HLHS – example of Fontan as final procedure
i. Cyanotic heart lesion
ii. Staged procedures
1. Norwood w/ BT shunt
2. Bi-directional Glenn
3. Fontan
g. Norwood with BT Shunt - Creation of RV to aorta pathway
i. Converts the right ventricle into the main ventricle pumping blood to both the lungs and the body
ii. Aorta is constructed from the base of the pulmonary artery and the narrowed aorta
iii. BT shunt gets blood back to the lungs
iv. Overall mixing (single system) with sats ~80s%
h. Bidirectional Glenn Procedure
i. SVC is divided w/ top portion connected to PA
1. Remove BT shunt
ii. Goal: reduce the volume load on the hypertrophied single ventricle that pumps in parallel to the
pulmonary and systemic circulations
iii. RV pumps to aorta and venous blood flows (from upper part of body) goes directly to lungs
iv. Aorta now sends more oxygenated blood to body
v. Note: upper half of return is going straight to lungs and only the blood from the lower legs is going
straight to the heart to get mixed in
i. Fontan Completion
i. IVC is connected to the RPA either through the heart or via a Gore-tex tunnel (extracardiac conduit)
ii. Glenn is left in place
iii. So what’s happening now?
1. IVC & SVC return blood to the PA (all deoxygenated blood goes straight to the lungs)
2. Blood returns from lungs to PV → LA → ASD to RA → RV → Aorta and O2 blood to body

j. Cardiac Transplant
i. Adult patients w/ repaired CHD with progressive heart failure
 1. Also see in kids w/ severe CHD (e.g. pulm atresia, heterotaxy, TAPVR, severe valve disease) or
who have failed repairs
ii. PAH – with high, unmodifiable pulmonary vascular resistance can be contraindication → (if yes, think
heart-lung transplant)
iii. Complications
1. Immunosuppression/infection
2. Diabetes, HTN, hyperlipidemia
3. Cardiac allograft vasculopathy (CAV) – form of aggressive atherosclerosis. Characterized by
neointimal proliferation of vascular smooth muscle cells → concentric narrowing of vessels silent
MIs. Not affected by immunosuppression.
iv. Pimp fact – vagus nerve is severed in transplant. So transplanted can’t respond to medications to block
parasympathetic (e.g. adenosine treating bradycardia, must use isoproterenol). Can require pts to need
pacemaker
9. Sequelae of CHD
a. Congestive Heart Failure
i. Left or right sided (depends on physiology)
ii. Treat underlying cause of heart failure
1. Use medications such as diuretics, ACEI, BB, etc.
iii. Risk factors: e.g. sustained arrhythmia, hyperthyroidism
1. Volume overload – pregnancy, valvular regurgitation, LR shunts
b. Cyanosis
i. Desaturation can come from mixing or shunting of arterial/venous blood
ii. Can cause increased or decreased pulmonary blood flow
iii. Hypoxemia → ↑epo production → ↑RBC volume
iv. Clinical sequelae:
1. Hyperviscosity, platelet dysfunction (clotting) & bleeding tendencies, hypertrophic
osteoarthropathy
v. Tx: ?oxygen therapy for pulmonary vasodilatory effect, tx underlying heart lesion
vi. Hyperviscosity Syndrome
1. Patients have secondary erythrocytosis syndrome
2. This increases blood viscosity
3. Clinical s/s: HA, faintness, dizziness, fatigue, altered mentation (from decreased cerebral blood
flow), visual disturbances, paresthesias, tinnitus, and myalgias
4. Tx: Therapeutic phlebotomy symptoms arise or HCT > 75%
vii. Arthritic
1. Hypertrophic osteoarthropathy - syndrome of clubbing of the digits, periostitis of the long
(tubular) bones, and arthritis
a. Clubbing
b. Periostitis - Subperiosteal new bone formation exists along the distal diaphysis of
tubular bones, progressing proximally over time
c. Osteoarthritis & also increase risk of gout
2. Schamroth’s sign: There is no diamond-shaped window when the dorsal surfaces of
corresponding finger of each hand are opposed
c. Pulmonary Hypertension
i. Multiple causes:
1. Pulmonary overcirculation – can increase pulmonary arterial pressure
2. Pulmonary vasoconstriction
3. Pulmonary vascular disease
ii. Explains why push to do corrective surgery at a young age
iii. Progressive and can be high morbidity
iv. Difficult to tx:
 1. Tx underlying heart disease
2. Oxygen
3. Phosphodiesterase 5 inhibitors (e.g. Viagra)

d. Eisenmenger Syndrome ★
i. Note: question will have a child from a different country…..(because we fix this in developed countries)
ii. Triad: systemic-to-pulmonary communication, pulmonary arterial disease, and cyanosis
iii. Occurs when pulmonary obstructive vascular disease reverses a L→R shunt to a bidirectional (L→R &
R→L)
iv. Usually occurs in unrepaired CHD
1. Systemic to pulmonary circulation connection that leads to pulmonary hypertension and
eventually a right-to-left or bidirectional shunt
2. E.g. VSD, ASD, PDA → become cyanotic in teens/20s
3. Patho: Arteriolar medial hypertrophy, intimal proliferation, and fibrosis from over-circulation →
obliteration of the pulmonary vascular bed
v. This example caused by large VSD
vi. A L→R shunt over time (left unrepaired) now puts more pressure on RV → RV hypertrophy → ↑pulm
artery pressures
vii. Pulm arteries show intimal hyperplasia, medial hypertrophy and secondary luminal thrombosis
viii. Ultimately develop bidirectional shunt
ix. Decreasing incidence given earlier surgeries/repairs
x. Clinical s/s: usually related to cyanosis & pulmonary HTN
1. Arrhythmia, hemoptysis, VTE, syncope, CHF, central cyanosis, endocarditis, clubbing
xi. Tx:
1. Meds: endothelin receptor antagonist (bosentan) or PDE inhibitor (sildenafil)
2. Lung transplant + repair cardiac defect (or heart transplant)
e. Cardiac Arrhythmias
i. Major clinical challenge
ii. Can worsen as they age
iii. Present with almost every CHD
iv. E.g. atrial flutter, atrial fibrillation, complete heart block, ventricular tachycardia, sinus node dysfunction
f. Infective Endocarditis (FYI)
i. CHD more at risk
ii. Risk factors: prosthetic heart valves or prosthetic material used for valve repair, prior hx of IE, persistently
cyanotic, residual defects from a repair, cardiac transplant and 6 mo after a prosthetic material repair
iii. Indications for antibiotics for dental procedures
g. Neurodevelopmental Disability
i. Risk factors: severity of the lesion (?oxygen levels), open heart surgery, syndromes.
ii. Deficits:
1. mild cognitive impairment
2. impaired social interaction
3. impairments in core communication skills,
4. inattention, impulsive behavior
5. impaired executive function
iii. Causes: ? Open heart surgery may result in cerebral macroemboli & microemboli to the central nervous
system or a period of global cerebral ischemia
10. Transitions into Adult Care
a. Kids w/ CHD grow up and live into adulthood
i. Adolescence is tricky
ii. May have concomitant mood d/o, social issues
 b. Goal: provide developmentally appropriate care to move adolescent into adult health care model
c. Shift responsibility of care from adult to patient
d. Integrate patients into medical home with multidisciplinary care (e.g. social worker, cardiologist, PCP, etc.)
e. Create a medical passport for patient to carry
i. Diagnosis, PMHx & PSHx, Meds, Allergies, Emergency Care plan
ii. Endocarditis prophylaxis plan

11. General CHD Recommendations

a. Pregnancy
i. CONSULT A SPECIALIST IN ACHD!
1. Discuss possible need for anticoagulation
2. Discuss genetics of CHD
ii. Cyanotic CHD – 32% incidence of maternal cardiovascular complications & 37% incidence of fetal
prematurity
1. Those with resting sats > 85% fare better
iii. Contraindicated in Eisenmenger syndrome
1. ~50% maternal and 60% fetal mortality
iv. Outcome usually favorable in disease with good functional status and systemic ventricular function
v. Estrogen containing OCP not recommended in those with
1. Cyanosis from intracardiac shunt
2. Severe PAH
3. Fontan repair
b. Exercise
i. Competitive sports should be avoided in cyanotic patients
ii. Depends on the lesion, but in general
1. Low to moderate intensity exercise safe
2. Caution with straining/lifting
c. Travel
i. Avoid dehydration
ii. Avoid prolonged sitting
iii. Supplemental oxygen may be considered for cyanotic patients during long-distance flights
iv. Virchow’s triad - endothelial injury, circulatory stasis, hypercoagulable state
12. General Cardiovascular Recommendations
a. Same as for every other adult
b. No smoking
c. Control risk factors (Obesity, HTN, DM, Cholesterol)
13. Summary:
a. ACHD is both adults diagnosed with CHD as adults and children with CHD now grown up
b. ASD - Wide and fixed split S2 murmur, L→R shunt, risk for atrial fibrillation as adults
c. VSD – presentation based on size of defect, smaller defects present as adults. L→R shunt
d. Coarctation of the aorta - HTN in UE, decreased lower extremity pulses
e. PFO – found when investigating stroke etiology. ?closure?
f. Congenital aortic stenosis – likely from bicuspid valve. SEM with radiation to the carotids
g. Eisenmenger – triad of systemic-to-pulmonary communication, pulmonary arterial disease, and cyanosis
h. Sequalae of CHD – arrhythmias, CHF, cyanosis, neurodevelopmental disability
These pts need multidisciplinary care with good transition of care.
LECTURE 13: CARDIAC CATHETERIZATION
Cardiac Catherization
 Definition: Radiopaque catheter is inserted into a peripheral vessel and passed under fluoroscopic control into the heart
 Patient Prep: consider co-morbidities, ECG, renal function, CBC, aspirin 2 hrs prior, stop anti-coags 2 days prior
 Femoral Approach: **high risk of retroperitoneal hematoma (hemoglobin will drop, “I can’t feel my legs”)**
o If someone’s bleeding you put pressure north of the puncture site due to the angle that you insert the needle
 Radial Approach: safer & preferred
 Right-sided heart catheterization – via a vein
o Pathway: SVC or IVC → RA → RV → PA, creating a wedge
o Indications: measures pressure , HF, PTN, O2 sats (looks at shunts)
 Left-sided heart catheterization – via an artery
o Get into the coronary ostium and shoot down dye to detect a blockage
o Can also go down into the LV to measure LVEDV
o Indications: MI or blockages
 Absolute CI: mentally incompetent or refuses consent
 Risks & Complications: fairly low – bleeding, MI, TIA, death (rare)
Coronary Angiography: gold standard for diagnosis of coronary artery disease
 Technique: gain access, perform, LVgraphy & measurement of LV pressures
 Risks & Complications: fairly low – bleeding, MI, TIA, death (rare)
Coronary Artery Disease: > 50% diameter stenosis in one or more vessels – must be > 70% to stent

LECTURE 14: ACUTE CORONARY SYNDROME

STEMI: new ST elevation at the J point in at least 2 contiguous leads

 **Coronary Arteries**
o II, III, avF: Inferior MI (RCA)
o V1-V4: Anterior MI (LAD)
o I, avL, V5-V6: Lateral MI (LCX)
NSTEMI: no persistent ST elevation

 Cardiac enzymes elevated = NSTEMI vs. not = Unstable Angina

 Don’t give fibrinolytics to NSTEMI pts

Risk Factors: Smoking, DM, elevated total/LDL cholesterol, low HDL cholesterol, HTN, CAD FHx
Pathophysiology of Atherosclerosis
 Endothelial Dysfunction, fatty streak, stable (fibrous) plaque, unstable plaque
o If the fibrous cap ruptures, the platelets adhere, activate, & aggregate
  Pop out GP IIb-IIIa receptors → thrombus
 ADP & TXA2 receptors perpetuate the clot
 **ADP Receptor Antagonists: Clopidogrel (Plavix), Prasurgrel, Ticagrelor
 TXA2 Receptor Antagonist: Aspirin**
S/Sx: pain (pressure, burning), sympathetic response (sweats, tachy), parasympathetic (N/V), fever, etc.
 If it’s the same kind of chest pain for 3 weeks, then it’s probs not an ACS
DDx:
 Pericarditis: Sharp, pleuritic pain; friction rub, relieved when sitting forward, diffuse ST elevation with PR depression
 Aortic Dissection: really bad pain radiating through to the back, associated with Marfan’s
 Pulmonary Embolus: #1 diagnostic sign is tachycardia
 PNA: Cough, sputum, fever, consolidation changes
 Esophageal spasm: #1 missed dx for ACS, retrosternal burning, after meals or at night
Atypical presenters: women, elderly, DM, dyspnea, syncope, lethargy, pain in the back, diaphoresis
Serum Markers
 CK-MB: elevated after injury to cardiac tissue, converts ADP to ATP
o Rises 4-8 hours after MI, peaks by 24 hours, returns to normal in 48-72 hours

 Troponin: Powerful marker of myocyte damage – VERY sensitive & specific

o Rises 3-4 hours, peaks 18-36 hours, returns to normal in 10-14 days
o Other events with elevation: CHF, ICU, renal failure, CVA, myocarditis
Approach to ACS – time sensitive with specific goals
 **Door to ECG is 10 minutes → to balloon is 90 minutes or to needle is 30 minutes (if you can’t do PCI within 120 minutes)**
o Do PCI within 12 hours of sxs onset for STEMI pts and cardiogenic shock or acute severe HF pts regardless of time
 Don’t do it in a noninfarcted artery in pts with STEMI who are hemodynamically stable
 Fondaparinux shouldn’t be used as sole anti-coag due to risk of catheter thrombosis
 Fibrinolytics: loading dose of P2Y12 receptor should be given asap (clopidogrel, prasurgrel, ticagrelor)
 If you get a stent put in, you have to be on ASA for the rest of your life and an ADP-R antagonist for 1 year
 Proves an issue for surgery – you have to be off the medication 5-7 days prior
 NOTE: Prasurgrel is contraindicated in pts with previous strokes, and you can’t load with it
 NOTE: ASA dosage with Ticagrelor MUST be 81 mg
 ** ASA & Clopidogrel should be administered in pts with STEMI who get fibrinolytic therapy**
 If suspected ACS: MONA (morphine, oxygen, NTG, aspirin), pull serial EKGs, monitor
 Morphine: ubiquitous effects – reverse with Narcan
 Oxygen: Supplemental if arterial O2 < 90% or respiratory distress
 Nitrates: CI: hypotension, bradycardia, PDE use (24 hours for Viagra, 48 hours for Cialis), suspected RV infarct
 Aspirin: 4 x 81 mg chewed
Beta Blockers: should be given in the first 24 hours in patients w/ ACS
Statins: pleiotropic effect
Secondary Prevention: BP < 140/90, LDL < 100, TG < 200, A1c < 7%, smoking cessation, physical activity, diet

LECTURE 15: COMPLICATIONS OF ACUTE CORONARY SYNDROMES

**Big right infarct with a blowing holosystolic murmur, you have mitral regurgitation because you’ve blown a papillary muscle**
 Pathognomonic for an inferior MI
If you see someone that hemodynamically collapses, it’s a death sentence – if you blow your LV you’re done
Recurrent Angina: post-infarction angina without reinfarction
 Structural: in-stent thrombosis
LV Failure/Cardiogenic Shock: “always think LAD”
 Degree of dysfunction correlates with the extent and location of myocardial injury
 Non-infarcted myocardium can be temporarily “stunned” → hypo/akinesis
Thromboembolism: Most common in large anterior MI – consider EF < 30%
Bradycardia mostly seen on right side of heart (RCA, inferior wall MI) vs. Tachycardia seen on either side
 SA node & AV node supplied by RCA, Bundle of His supplied by LAD
VT/VF (“if your electrical activity is starting in the ventricles you’re in bad shape”)
 Defibrillation, CPR, Amiodarone 300mg IV
PVC: in an MI, you’ll have a scar that’ll cause electrical instability/PVCs
 Suppression does not provide mortality benefit – you just monitor
Mobitz type II 2 degree AV node block – gets closer to the AV node, so you want to treat
nd

Complete AV block – you need to insert a pacemaker

Interventricular Septal Rupture – seen with LAD infarcts
Free Wall Rupture – you’re dead
Pericarditis: diffuse ST segment elevation with PR depression, **Dressler’s syndrome (2-4 weeks post-MI)**