Cardiovascular Disease – Part 1 - UCSF CME · 2013-07-02 · 1 UCSF Internal Medicine Board...

UCSF, Department of Medicine, CME

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UCSF Internal MedicineBoard Certification and Recertification Review

Cardiovascular Disease – Part 1

Andrew Boyle MBBS, PhD

July 2013

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From ABIM blueprint for Internal Med Board Exams

UCSF, Department of Medicine, CME 3

CASE 1: 45 y.o. male, with no PMH, presents with chest pain x 8 hours


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Case 1: What is the next step?

1) Start aspirin and heparin therapy

2) Start aspirin, low dose heparin and lytic therapy

3) Perform cardiac catheterization

4) Perform echocardiogram

5) Not sure


Acute Pericarditis

Characterized by pleuritic, positional chest pain, a rub, possibly a small pericardial effusion, EKG with diffuse ST-elevation and PR-depression, and PR-elevation in aVR

Cardiac enzymes can be elevated

Usually responds to oral NSAIDs

Thrombolytics may result in life-threatening hemorrhagic tamponade


Question 2: Thrombolytic therapy is a strict contraindication in all of

the following except:

1) Presence of AV-malformations in the brain

2) Any prior history of embolic stroke3) Recent GI bleed within 1 month4) Patient with metastatic disease to the

brain5) All of the above


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Absolute Contraindications

• Any prior intracranial hemorrhage

• Known structural cerebral vascular lesion (e.g., arteriovenous malformation)

• Known malignant intracranial neoplasm (primary or metastatic)

• Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours

• Suspected aortic dissection

• Active bleeding (excluding menses)

• Significant closed-head trauma or facial trauma within 3 months

ACC/AHA Guidelines 2004

Contraindications and Caution with Lytic Therapy


• History of chronic, severe, poorly controlled hypertension

• Severe uncontrolled hypertension on presentation (SBP > 180 mm Hg or DBP > 110 mm Hg)

• History of prior ischemic stroke greater than 3 months, dementia, or known intracranial pathology not covered in contraindications

• Traumatic or prolonged (> 10 minutes) CPR or major surgery (< 3 weeks)

• Recent (< 2 to 4 weeks) internal bleeding

• Noncompressible vascular punctures

• For streptokinase/anistreplase: prior exposure (> 5 days ago) or prior allergic reaction to these agents

• Pregnancy

• Active peptic ulcer

• Current use of anticoagulants: the higher the INR, the higher the risk of bleeding

Relative Contraindications To Lytics



Case 3: 57 year old diabetic with dyslipidemia

A 57-year-old woman with adult-onset diabetes mellitus has the following lipid profile:

Total serum cholesterol of 178 mg/dLLDL cholesterol level of 98 mg/dLHDL cholesterol of 35 mg/dLTriglyceride level of 592 mg/dL


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Case 3

Has been compliant with a low-fat, low-cholesterol, diabetic diet.

Glycohemoglobin A1C = 6.6% on oral therapy.


Case 3: Which of the following is the recommended initial drug therapy

for this patient?

1. A fibrate

2. Niacin

3. A statin

4. Ezetimide

5. A bile acid resin


Major Risk Factors for CV Disease

4 major modifiable traditional CV risk factors: Smoking

Diabetes Mellitus

Hypertension

Hyperlipidemia

80-90% patients with CAD have 1 CAD RF; >95% with a fatal CAD event had 1 CAD RF.

JAMA, August 20, 2003, vol 290, pp.891-97, 898-904.


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Hyperlipidemia in Diabetics

Diabetes mellitus is a coronary artery disease equivalent, and risk factor targets for patients with diabetes are the same as those in patients with established coronary disease.

This is irrespective of age or other risk factors.


Log-Linear Relationship Between LDL-C Levels and Relative Risk for CHD

3.7

2.9

2.2

1.7

1.3

1.0

40 70 100 130 160 190

Relative Risk for Coronary

Heart Disease (Log Scale)

LDL-Cholesterol (mg/dL)

Grundy, S. et al., Circulation 2004;110:227-39.


Pharmacologic Hypolipidemic Therapy

Goal is to reduce LDL <100 mg/dL (optional <70 mg/dL); a statin is the recommended initial agent.

If TG is very high (≥500 mg /L), treat this before the LDL to prevent pancreatitis.

Prevalence of abnormal HDL and TG in CAD:60% with HDL <40; 30% with TG >200.


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Risk Category LDL-C Goal Initiate TLCConsider

Drug Therapy

High risk:CHD or CHD risk equivalents (10-year risk >20%)

<100 mg/dL (optional goal:

<70 mg/dL)

100 mg/dL >100 mg/dL(<100 mg/dL: consider drug

options)

Moderately high risk:2+ risk factors (10-year risk 10% to 20%)

<130 mg/dL 130 mg/dL >130 mg/dL(100-129 mg/dL: consider drug

options)

Moderate risk:2+ risk factors (10 year risk <10%)

<130 mg/dL 130 mg/dL >160 mg/dL

Lower risk:0-1 risk factor

<160 mg/dL 160 mg/dL >190 mg/dL(160-189 mg/dL:

LDL-lowering drug optional)

ATP III LDL-C Goals

Grundy, S. et al., Circulation 2004;110:227-39.




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Treatment Options

Statins: modest effects on TG, HDL. Fibrates ↓TG 20-50%, ↑HDL 10-20%.

VA-HIT Study: Gemfibrozil reduced MI/ cardiac death.

Niacin: ↓TG 20-50%, ↑HDL 20-35%. Omega-3 fatty acids: ↓TG 20-30%, ↑HDL 1-

3%. Ezetimide is an intestinal brush border

cholesterol absorption inhibitor. May be added to a statin if the target LDL goal not achieved.


Case 4: 72 yo woman with NSTEMI

A 72-year-old woman comes to the emergency department with several episodes of substernal chest pressure over the past 24 hours. She has had four episodes of chest pressure occurring at rest and lasting 20-40 minutes.

History of hypertension, diabetes, and current smoking. Over the past day,

Medications include aspirin 325 mg daily; hydrochlorothiazide 25 mg daily; and glyburide 5 mg twice daily.


Case (cont’d)

Vital signs: pulse is 80/min and regular, blood pressure is 145/75 mmHg. Chest with basilar crackles and cardiac examination reveals a + S4.

ECG shows 2-mm ST-segment depression in leads V3-V6.

Serum troponin I is elevated at 3.7 ng/mL.


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Case 4

1. Schedule an exercise stress test within 48 hours.2. Begin intravenous heparin.3. Begin intravenous heparin and eptifibatide, and

schedule an exercise stress test within 48 hours.4. Begin intravenous heparin and eptifibatide, and

schedule coronary angiography within 48 hours.

Therapy with aspirin, sublingual nitroglycerin, and a β–blocker is begun. The patient is admitted to the coronary care unit.Which of the following should you do next?

Spectrum of Acute Coronary Syndromes

StableAngina

UnstableAngina

Non-Q wave MI

Q waveMI

ST Elevation MINon ST Elevation ACS ECG - ST

CK-MB

Troponin I or T

CRP

ECG - ST


TIMI Risk Score For UA/NSTEMI7 Independent Predictors

1. Age > 65 years

2. > 3 CAD risk factors (high cholesterol, family history, hypertension, diabetes, smoking)

3. Prior coronary artery disease (stenosis > 50 %)

4. ST-segment deviation on the ECG

5. > 2 anginal events < 24 hours

6. ASA in last 7 days

7. Elevated cardiac biomarkers (troponin or CK-MB)

Antman et al, JAMA 2000; 284 : 835-842.


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TIMI Risk Score For UA/NSTEMIUFH Group TIMI 11B (N= 1957)

4.78.3

13.219.9

26.2

40.9

0

10

20

30

40

50

0-1 2 3 4 5 6-7

D/M

I/Urg

Rev

asc

(%)

Number of Risk Factors

% Pts: 4.3 17.3 32.0 29.3 13.0 3.4

2 trend P <0.001

Antman et al, JAMA 2000; 284 : 835-842.


EARLY INVASIVE STRATEGY

Class I IndicationsAny of the high-risk indicators (Level of Evidence: A)

a) Recurrent angina at rest/low level activity despite Rx

b) Elevated Troponin

c) New ST-segment depression

d) Rec. angina/ischemia with CHF symptoms

e) Positive stress testf) EF <0.40 g) BP h) Sustained VTi) PCI <6 months, prior CABG

UA/NSTEMI 2002

14.5

24.2

16.914.3

0

5

10

15

20

25

30

TnT - TnT +

(%)

CONSERVATIVE INVASIVE

TACTICS: Troponin T: at 6 months

TnT cut point = 0.01 ng/ml (54% of Pts TnT +)

Death, MI, Rehosp ACS at 6 Months

OR=0.52*p<0.001

InteractionP<0.001

p=NS

*

N=414 N=396 N=463 N=495

Cannon, AHA, Nov 15, 2000, New Orleans, LA.


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11.8

20.3

12.816.1

19.5

30.6

0

5

10

15

20

25

30

35

Low 0-2 Intermed. 3-4 High 5-7

De

ath

/MI/

AC

S R

eh

os

p (

%)

TIMI Risk Score

CONS

TACTICS: TIMI UA Risk Score at 6 months

% of Pts: 25% 60% 15%

INV

OR=0.75CI (0.57, 1.00)

de Winter RJ et al. N Engl J Med 2005; 353:1095-1104.

ICTUS: Major results at one year

End point Early invasive strategy (%)

Selective invasive strategy (%)

p

Death/MI/rehospitalization for angina

22.7 21.2 NS

Death 2.5 2.5 NSMI 15.0 10.0 0.005Rehospitalization for angina

7.4 10.9 0.04

Invasive versus Conservative Treatmentin Unstable Coronary Syndromes

“optimal medical therapy: Aspirin, enoxaparin, clopidogrel, atorvastatin”

Relative-Risk of all cause Mortality:A meta-analysis of contemporary trials

(FRISC-II, ICTUS, ISAR-COOL, VINO, RITA-3, TIMI-18, TRUCS)

Bavry AA et. al. JACC 2006;48:1319-25


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Case 4 Evaluation

TIMI Risk Score 6/7 = high-risk.

Early coronary angiography is preferred strategy with treatment with GP IIb/IIIa receptor inhibitor.


Cardiac Catheterization


Case 5: 75 year old woman with NSTEMI

A 75-year-old woman with no past medical history presents to the ED 4 hours after the onset of stuttering, severe substernal chest pain with radiation to the left arm and jaw.

After two sublingual nitroglycerin tablets, the patient is free of chest pain.

Electrocardiography reveals 2-mm ST-segment depression in leads II, III, and aVF.


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Case 5 (cont’d)

The initial troponin I level is elevated at 8 ng/mL.

The patient has no clear-cut medical contraindications to anticoagulation. The patient is treated with aspirin, intravenous β-blocker, and intravenous nitroglycerin.


Case 5: In addition to the medications that have been started, which of the following would be the most optimal management strategy at this time?

1. Unfractionated heparin2. Enoxaparin3. Clopidogrel4. Clopidogrel, unfractionated heparin5. Clopidogrel, enoxaparin, diltiazem


Therapies in NSTEMI

LMWH versus UFH?

Dual anti-platelet therapy – when and for how long to treat?

Bivalirudin?


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Therapies in NSTEMI

LMWH versus UFH?


Bivalirudin?


LMWH versus UFH in ACS

Advantages of LMWH: More predictable absorption (low degree of

protein binding)

More predictable anticoagulant effect (no need to monitor PTTs)

Higher activity against factor Xa

Fewer adverse effects, including thrombocytopenia


8.6 7.1 0.82 (0.69-0.97) 18 0.02

6.5 5.2 0.79 (0.65-0.96) 21 0.02

5.3 4.1 0.77(0.62-0.95) 23 0.02

1.8 1.4 0.80 (0.55-1.16) 20 0.24

B

B

B

B

0.5 1 2

Day

2

8

14

43

UFH(%)

ENOX(%)

OR(95 CI)

Favors ENOX

Favors UFH

% P

O.R.

TIMI 11B/ESSENCE Meta-analysis:Enoxaparin vs. Unfractionated heparin

Heterogeneity: All P=NS

Death or MI

Antman, Circulation 1999;100:1602-8.


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SYNERGYSuperior Yield of the New Strategy of

Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors

Primary end point

Enoxaparin Heparin Hazard ratio

95% CI

Death/MI (%) 14 14.5 0.96 0.86-1.06

The SYNERGY Trial Investigators. JAMA 2004; 292:45-54.

•10 000 high-risk ACS patients, median age = 68, 34% women•Randomized to enoxaparin or UFH •>90% of patients went to the cath lab early (median of 21 hrs)•57% received a IIb/IIIa blocker•66% received clopidogrel

SYNERGY - Bleeding Events


Antman et al, JAMA 2000; 284 : 835-842.

Enoxaparin UFH P-value(n = 4993) (n = 4985)

GUSTO severe 2.9 2.4 0.106

TIMI major - clinical: 9.1 7.6 0.008

CABG-related 6.8 5.9 0.081Non-CABG-related 2.4 1.8 0.025H/H drop - algorithm 15.2 12.5 0.001

Any RBC transfusion 17.0 16.0 0.155

ICH < 0.1 < 0.1 NS


Therapies in NSTEMI

LMWH versus UFH?


Angiomax?


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Primary End Point ‐MI/Stroke/CV Death

This image cannot currently be displayed.

Clopidogrel+ ASA*

3 6 9

Placebo + ASA*

Months of Follow-Up

11.4%

9.3%

20% RRRP < 0.001

N = 12,562

0 12

* In combination with standard therapy

The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.

Fox et al. Circulation. 2004;110:1202-1208.

Medical Rx Group

Placebo

Clopidogrel

RR: 0.80 (0.69-0.92)

0.20

4

0.15

0.10

0.05

0.0

100 200 300

Clopidogrel

0.20

4

0.15

0.10

0.05

0.0

100 200 300

PCI Group

Placebo

RR: 0.72 (0.57-0.90)

0.20

4

0.15

0.10

0.05

0.0

100 200 300

CABG Group

Placebo

Clopidogrel

RR: 0.89 (0.71-1.11)

CURE: Benefit by Revascularization

CV

D/M

I/St

roke

CV

D/M

I/St

roke

CV

D/M

I/St

roke


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Placebo + ASA*

N = 6303

Clopidogrel + ASA*N = 6259

CURE ‐ Bleeding Results

• Major bleeding 2.7% 3.7%**

Life‐threatening bleeding 1.8% 2.2% †

Non‐life‐threatening bleeding 0.9% 1.5% ‡

• Minor bleeding 2.4% 5.1% §

End Point

* In combination with standard therapy

** P = 0.001; † P = NS; ‡ P = 0.002; § P < 0.001.

The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.


Therapies in NSTEMI

LMWH versus UFH?

Plavix therapy – when and for how long to treat?

Bivalirudin?


Moderate-high risk

ACS

ACUITY Study Design

An

gio

gra

ph

y w

ith

in 7

2h

Aspirin in allClopidogrel

dosing and timingper local practice

Aspirin in allClopidogrel

dosing and timingper local practice

UFH orEnoxaparin+ GP IIb/IIIa

Bivalirudin+ GP IIb/IIIa

BivalirudinAlone

R*

*Stratified by pre-angiography thienopyridine use or administration*Stratified by pre-angiography thienopyridine use or administration

Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,800)

Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,800)

ACUITY Design. Stone GW et al. AHJ 2004;148:764–75ACUITY Design. Stone GW et al. AHJ 2004;148:764–75

Medicalmanagement

PCI

CABG


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Ischemic Composite Endpoint

0

5

10

15

0 5 10 15 20 25 30 35

Cu

mu

lati

ve E

ven

ts (

%)

Days from Randomization

Estimate P(log rank)7.3%UFH/Enoxaparin + IIb/IIIa (N=4603)

Bivalirudin + IIb/IIIa (N=4604) 0.377.7%

Bivalirudin alone (N=4612) 0.307.8%

UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin AloneUFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone


Major Bleeding Endpoint

0

5

10

15

0 5 10 15 20 25 30 35

Cu

mu

lati

ve E

ven

ts (

%)

Days from Randomization

Estimate P(log rank)5.7%UFH/Enoxaparin + IIb/IIIa (N=4603)

Bivalirudin + IIb/IIIa (N=4604) 0.415.3%

Bivalirudin alone (N=4612) <0.00013.0%

UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin AloneUFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone


Medical Therapy for UA/NSTEMI

Antianginal therapy: -blockers, nitrates.

Antiplatelet therapy: aspirin, clopidogrel, plus GP IIb/IIIareceptor inhibitors for high-risk patients.

Newer anti-platelet agents: prasugrel, ticagrelor. Equal to or better than clopidogrel, but more bleeding.

Antithrombotic therapy: UFH, LMWH, Direct Thrombin Inhibitors, Factor Xa inhibitor (Fondaparinux).

Secondary prevention: lifestyle modifications, ACEI, statins, glycemic control.


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Case 6: 63 y.o. woman with STEMI

A 63-year-old non-English-speaking woman comes to the emergency department because of severe, steady precordial discomfort that began 10 hours ago. She thought that the chest pain may have been indigestion, but she had no relief with an antacid.

She has a history of hypertension. She is taking no medications.


Case 6 (cont’d)

Her heart rate is 92/min, and her blood pressure is 150/90 mmHg. Her lungs are clear to auscultation and cardiac examination reveals an S4.

Her electrocardiogram shows 3-mm ST-segment elevation in leads II, III, and aVF.


Case 6 continued

She is given a chewable aspirin, morphine 4 mg intravenously, metoprolol 5 mg intravenously, and nitroglycerin 20 μg/min intravenously with a decrease in her chest pain intensity from severe to moderate.

A hospital in the next county (1.5 hours away by ambulance) recently established a program that provides 24-hour angioplasty services.


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Case 7: Which of the following should be considered in the decision of whether to

refer this patient for treatment?:

1. Thrombolysis has a better outcome than angioplasty (with or without stenting) in this patient.

2. Thrombolysis and angioplasty (with or without stenting) are equivalent in outcome for this patient.

3. Angioplasty (with or without stenting) has a better outcome than thrombolysis in this patient.

4. Neither thrombolysis nor angioplasty (with or without stenting) should be performed in this patient.


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Glagov’s Model of Vascular Remodeling

Glagov S et. al. NEJM 1987


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Angiography Cannot Account forCoronary Remodeling

3.1 mm

3.1 mm

IVUS

IVUS

Adopted from Kinlay, S.

Angiogram


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Plaque Rupture


TIMI Risk Score for STEMI

Age 65-74 75

DM/HTN or angina

Weight < 67 kg

Time to rx > 4 hrsAnterior STE or LBBB

HR >100SBP < 100

Historical

Exam

Presentation

Killip II-IV

2 points3 points1 point

3 points

2 points1 point

1 point1 point

2 points

Risk Score = Total (0 -14)Morrow DA, Circulation 2000; 102: 2031



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“The longer you wait, the worse the outcome”

Antman E. et al. 2004, ACC/AHA Practice Guidelines


STEMI Reperfusion Therapy

Efficacy of thrombolysis falls off significantly >6 hours after onset of symptoms. PCI preferred for late presentation AMI patients.


Coronary Flow Rates with Lytics


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Coronary Flow Rates with PCI


Reperfusion

The medical system goal is to facilitate rapid recognition

and treatment of patients with STEMI such that door-to-

needle (or medical contact–to-needle) time for initiation

of fibrinolytic therapy can be achieved within 30

minutes or that door-to-balloon (or medical contact–to-

balloon) time for PCI can be kept within 90 minutes.



Fibrinolytic Therapy

Advantages

Widely available

Rapid, simple

therapy

Cardiologist not

required

Limitations

1-2% intracranial

bleeding

~50% with slow/no flow

Rescue PCI at risk,

delayed


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Primary PCI

Limitations

Access

Delay in restoring

flow if transferred

Expense, logistics

Advantages

Highly successful

(~>95%)

Early risk stratification

Earlier discharge

Fewer intracranial

bleeds


Primary PTCA vs. Thrombolytic Therapy

For every 1000 pts treated, PTCA compared with lytic therapy:

20 lives saved43 re-MI prevented13 ICH prevented

Meta-analysis of 23 trials suggests that

primary PTCA is preferred over lytic

therapy

Keely et al. Lancet 2003


Cases when PCI preferred to Fibrinolysis

Contraindications to fibrinolysis: PCI shown to have high success rate

Lower one-year mortality compared to historical controls

Late presentation (>6 hours)

CABG patients

Cardiogenic shock


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Prior to PCI – totally occluded RCA


After PCI – RCA s/p stenting

Recommendations for Triage and Transfer for PCI (for STEMI)

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

NEW

Recommendation

Each community should develop a STEMI system of care following the standards developed for Mission Lifeline including:

• Ongoing multidisciplinary team meetings with EMS, non-PCI-capable hospitals (STEMI Referral Centers), & PCI-capable hospitals (STEMI Receiving Centers)



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Recommendations for Triage and Transfer for PCI (for STEMI) (cont.)

NEW

Recommendation

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

It is reasonable to transfer high risk patients who receive fibrinolytic therapy as primary reperfusion therapy at a non-PCI capable facility to a PCI-capable facility as soon as possible where either PCI can be performed when needed or as a pharmacoinvasive strategy.



Case 8: 52 y.o. man with angina

A 52 year-old man with type-2 diabetes mellitus, atrial fibrillation, hyperlipidemia, and hypertension presents to your office with a new symptom of exercise-induced chest tightness. He describes a squeezing substernal sensation with radiation down his left arm. The discomfort comes on reliably with 1-2 blocks of brisk walking and is relieved with rest.


Case 8 (cont’d)

Medications: metoprolol 50mg bid, amlodipine 10mg qd, ASA 81mg qd, Warfarin and fluvastatin 20mg qhs.

His resting blood pressure and pulse are 110/70 mmHg and he is in atrial fibrillation with a pulse of 90 bpm.


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Case 8: The next most appropriate step is to obtain:

1. Highly reactive CRP level to assist with risk stratification

2. Electron beam CT to determine degree of coronary calcification

3. Multislice Coronary CT scan

4. Invasive coronary angiography

5. No further diagnostic testing


Framingham Risk Score

Prognostic value for primary prevention population.

Includes the following variables: Sex Age Total cholesterol HDL Smoking (current) Systolic blood pressure Diabetes


C-Reactive Protein

C-reactive protein adds prognostic information to that conveyed by the Framingham risk score (Nurses Health Study).

Whether CRP is just a marker of inflammation, or a causal agent increasing the risk of MI awaits further investigation.

CRP most useful in providing further risk assessment in healthy men and women with an intermediate risk score.

Ridker P, et al. NEJM. 2002; 347: 1557-65.


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Case 8 Answer Critique

CRP: Patient should be on maximal RF modification regardless of CRP level.

EBCT: Unhelpful in patient with classic angina.

MultiSlice Coronary CT scan: not very reliable when: Irregular HR (such as A-fib) Tachycardia Elevated Calcium score Possibly prior stents (especially when

the vessel is small)


Case 9: 56 y.o. man with heart failure post-MI

A 56 year-old man is seen days following an acute ST-segment elevation myocardial infarction. At that time, he had atypical symptoms of epigastic pain and presented the hospital 12 hours after onset of pain with dyspnea.

In the ER, he was found to have ST-segment elevations in leads V1-V4 with elevated jugular venous pressure, hypoxia, and rales in both lung fields.

Following successful coronary stenting of the left anterior descending coronary artery occlusion, he was left with a significant anterior wall motion abnormality.


Case 9 continued

He is currently on ASA, metoprolol, clopidogrel, an ACE inhibitor and a statin.

An echocardiogram showed a persistent anterior wall motion abnormality with an overall left ventricular ejection fraction of 35%.


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Case 9 continued

Vital signs are BP 132/70 mmHg, HR 70 bpm, RR 18/minute, and O2 saturation 94% on room air. Physical exam reveals mildly elevated jugular venous filling pressure, a third heart sound, basilar crackles, with no peripheral edema.


Case 9: The most important medicine to add to his heart

failure regimen would be:

1. Low dose digoxin

2. Nitrates

3. Eplerenone

4. Hydralazine

5. Angiotensin receptor blocker


EPHESUS TRIAL --- STEMI, EF <40% and CHF

Death

Pitt B et al NEJM 2003; 348: 1309

Eplerenone 25 mg, up-titrated to 50 mg daily

K+


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Case 10: 64 y.o. man with new Heart Failure

CC: A 64 year-old man is hospitalized because of dyspnea and leg edema. He has a longstanding history of essential hypertension that is treated with a thiazide diuretic and amlodipine.


Case 10 continued

PE: HR 110, BP 180/98, RR 20, afebrile JVP 10 cm, basilar rales, S3, S4, no murmur, 2+ pitting edema

ECG: sinus tachycardia with LBBB

CXR: large heart, mild pulmonary edema

Labs: normal


Case 10 continued

Echocardiography shows left ventricular ejection fraction of 25%. He has mild mitral and tricuspid regurgitation with an estimated pulmonary artery systolic pressure of 40 mmHg.

He receives furosemide, three boluses of 60 mg intravenously and over a 24-hour period and improves rapidly with diuresis of 2,400 mL.


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Case 10: All of the following statements are true except:

1. Ischemic work-up should be undertaken2. Beta-blocker therapy should be initiated

irrespective of whether coronary artery disease is diagnosed

3. Ace-inhibitor therapy will decrease mortality4. Digoxin will improve symptoms and decrease

mortality5. Implantable defibrillator should be

considered if the ejection fraction remains <35% despite medical therapy


AHA/ACC Heart Failure Guidelines: Stages of Heart Failure

A: Patients at high risk of developing heart failure because conditions associated with heart failure are present, but with no overt structural/functional abnormalities of the heart and no heart failure symptoms or signs Examples: Hypertension, diabetes mellitus,

coronary heart disease, cardiotoxin exposure, family history of DCM, past rheumatic fever, hemochromatosis



B: Patients with overt heart disease that is strongly associated with developing heart failure but who have never shown signs or symptoms of heart failure Examples: Ventricular hypertrophy, cardiac

chamber dilation, asymptomatic valve disease, prior MI or angina


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C: Patients with prior or current symptoms of heart failure associated with structural heart disease Examples: Dyspnea, fatigue, fluid retention or other

signs and symptoms due to cardiac dysfunction

D: Patients with advanced structural heart disease and marked symptoms of heart failure at rest despite maximal treatment and require specialized interventions Examples: Frequent CHF hospitalizations, hospital

bound on inotropes, heart transplant candidate, hospice patient


When evaluating a patient with heart failure, keep a wide differential in mind:


Medical Management of HF (1)

-blockers: indicated in patients with LV systolic dysfunction irrespective of CAD

ACEIs: indicated in patients with LV systolic dysfunction without a contraindication

ARBs: for patients intolerant to ACEIs - Cough with ACEIs in 5-10% of white patients of European descent; up to 50% of Chinese patients; non-productive; usually appears within first months of therapy; disappears within 1-2 weeks of discontinuation of therapy; re-appears within days of re-challenge.


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Medical Management of HF (2)

Nitrates/hydralazine: for patients intolerant to ACEIs/ARBs (i.e., renal insufficiency); or, in addition to optimal therapy in African-American patients (A-HeFT Trial).

Digoxin: decreases HF symptoms and reduces rehospitalization.

Diuretics: Loop diuretics: for symptoms of congestion Thiazide diuretics: for concomitant hypertension Aldactone: beneficial in patients with severe class III-IV

HF (Rales trial) and in patients with AMI and LV dysfunction (EPHESUS trial)


Sudden Cardiac Death in Heart Failure (SCD-HEFT) Trial

Benefit of ICD in both ischemicand non-ischemic CMP

Bardy GH et al, NEJM 2005


Case 11: 43 year old man with severe chest pain

Sudden onset of severe, crushing, retrosternal chest pain.

His initial ECG showed sinus tachycardia with anterior lead ST-segment elevation.

Five hours after the onset of pain, he received thrombolytic therapy in the emergency department with only transient relief.

He now has progressive dyspnea and is unable to lie flat.


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Case 11 cont’d

Physical examination: pulse 150/min with occasional irregularity, respirations labored at 28/min, and blood pressure is 98/80 mm Hg.

He appears diaphoretic, ashen, and apprehensive.

Jugular venous pressure cannot be estimated, carotid pulsation is thready, and the lungs have crackles bilaterally.

Cardiac examination reveals a soft first heart sound, a soft, widely split second heart sound, and a third heart sound, but no murmur.


Case 11 ECG: 1 hour after lytics


Case 11: This patient is most likely experiencing which of the

following complications?

1) Pericarditis. 2) Ventricular septal rupture. 3) Free wall rupture. 4) Cardiogenic shock. 5) Ventricular tachycardia.


34


Cardiogenic Shock

5-15% STEMI cases.

When AMI involves >40% of myocardium.

In-hospital mortality 50%.


Management

Intubation.

Pressors. Dopamine

Dobutamine

Levophed

Primary PCI.

IABP.


Case 12: 38 year-old woman with chest pain

To the ED with severe retrosternal CP. She reports that this is the fourth such

episode in the last week, the previous episodes having terminated spontaneously.

She has no risk factors for coronary artery disease but does have a history of migraine headaches.


35


Case 12 cont’d

Physical examination: pulse of 110/min, blood pressure of 140/90 mm Hg.

ECG shows 2-mm ST-segment elevation in leads V1-V3, with reciprocal depression in leads II, III, AVF.

The pain resolves within minutes of sublingual nitrate administration and a repeat electrocardiogram shows complete resolution of the ST-segment changes.


Case 12: Which of the following is the most likely

pathogenesis?

1) Pericarditis.

2) Coronary artery dissection.

3) Coronary thrombosis.

4) Coronary vasospasm.

5) Esophageal spasm.


Prinzmetal’s Angina

Younger women. Associated with vasospastic disease

(i.e., migraine HA). Diagnosis: History of nitrate-responsive CP, no CAD. ECG during pain Holter study Ergonovine provocation in cath lab


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Spontaneous Coronary Dissection

Rare condition associated with pregnancy

High morbidity

PCI preferred

Longterm aspirin, beta-blockers.


Case 13: 44 year-old man presents for the first time to your clinic for routine visit

Has no complaints.

No prior medical history.

No medications.

PE: Chest CTA, RRR, physiologic split S2, no murmur.

Since it is the first visit, a routine EKG is performed.


Case 13: ECG


37


Case 13: Which of the following is the

most appropriate next step?

1) Chest X-ray.

2) Exercise stress electrocardiography.

3) Dipyridamole radionuclide imaging.

4) Electron beam CT.

5) Repeat the EKG.


Incorrect Lead Placement

Remember to check for axis:

- QRS axis

- P-wave axis


EKG – correct precordial lead placement


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Case 14: 65 year-old woman to ED with severe CP

CP began suddenly 2 hours ago while lifting boxes. She is not short of breath, but she is nauseated. The pain has not been relieved by oxygen or nitroglycerin.

PMHx: poorly controlled hypertension, chronic renal insufficiency, and current smoking.


Case 14 cont’d

PE: blood pressure 100/52 mm Hg in both arms, pulse 120/min and regular. Remainder of his physical examination unremarkable.

ECG: sinus tachycardia, left ventricular hypertrophy, and no ST segment changes.


CXR


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Case 14: Which of the following diagnostic tests

should be done next?

A) Transthoracic echocardiogram. B) Emergent coronary angiogram. C) Transesophageal echocardiogram. D) Gastrograffin esophageal swallow.


Thoracic Aortic Dissection

Risk Factors: hypertension, atherosclerosis, Marfan’s, connective tissue disease .

History: severe, sudden, abrupt onset; tearing quality with radiation to the back.

PE: AI, unequal peripheral pulses uncommon.

ECG: LVH.

CXR: widened mediastinum (PPV 50%).


Aortic Dissection Diagnosis

Rapid diagnosis critical.

TEE, contrast CT, aortography, or MRI.


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Case 15: 55 year-old man with CAD, ESRD, HTN with CP

CP at rest, no improvement with NTG.

PE: anxious and diaphoretic. HR 80/min and regular, BP 85/55 mm Hg, and falls by 12 mm Hg during inspiration. CVP 12. Remainder unremarkable.


Case 15: ECG


Case 15 cont’d

RA 12 mm Hg

RV 16/10 mm Hg

PA 16/12 mm Hg

PCW 8 mm Hg

CI 1.6 L/min/m2.


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Case 15: What is the most likely diagnosis?

1) Pulmonary embolism. 2) Acute pericarditis. 3) Fluid overload. 4) Right ventricular infarction. 5) Pericardial tamponade.


RV Infarction

RCA occlusion, proximal to RV marginal branches.

Triad of hypotension, elevated CVP, clear lung fields.

Pulsus paradoxus may be present.

ECG: STE in RV4.


Tamponade

Same triad of hypotension, elevated CVP, clear lungs.

No STE on ECG (or diffuse if pericarditis).

Echocardiography to differentiate MI versus pericarditis with tamponade.


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Case 16: 70 year-old man with 90 minutes of CP


Case 16: In addition to aspirin, which of the

following is the best management strategy?

1) Percutaneous coronary intervention. 2) Nitrates, β-blocker, and angiotensin-

converting enzyme inhibitor. 3) Thrombolytic therapy and intravenous heparin. 4) Half-dose thrombolytic therapy, glycoprotein

IIB/IIIa receptor inhibitor, and heparin.


Posterior MI

LCx or distal branch off RCA occlusion.

Prominent R waves V1-3.

Horizontal ST-depression V1-3.

Posterior leads often helpful.


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Occluded LCx/OM


s/p PCI


Post-PCI ECG


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Should Gp IIb/IIIa inhibitors be

given in addition to lytic therapy?


Primary Endpoint: 30 Day Mortality

Days

% M

ort

ali

ty

5.9%

5.6%

p = 0.43 for superiority

Std. Reteplase (n = 8260)Abciximab + Dose Reteplase (n = 8328)

GUSTO V AMI

Non-Inferiority RR 0.95(95% CI, 0.84-1.08)

Lancet 2001; 357:1905-14


0.5

1.1

0.4

1.2

0.3

1.5

0.4

2.1

0

1

2

3

% o

f P

atie

nts

Std. Dose Reteplase (n = 8260)

Abciximab + Dose Reteplase (n = 8328)

p = 0.66

< 70 yrs > 75 yrs> 70 yrs < 75 yrs

ICH by Age Group

* Significant treatment interaction for the age 75 dichotomy; p = 0.033

p = 0.53

p = 0.27*

p = 0.069*

12/1088 24/114928/717937/717225/2030 31/213521/619324/6230

Lancet 2001; 357:1905-14

Prespecified Age 70 Analysis / Post-Hoc Age 75 AnalysisGUSTO V AMI


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Case 17: 46 y.o. female collapses in the ER (BP 180/88)


Case 17: What is the next best therapeutic test:

1) Cardiac echocardiography to rule out tamponade

2) Chest CT to rule out dissection

3) Head CT to rule out hemorrhage

4) Cardiac catheterization/PCI

5) None of the above


Case 18: 18 y.o. male presents to the clinic for routine

examination

He has no prior medical history and takes no medications

He is very active in sports and wants a medical clearance letter from you to participate in varsity college basketball

PE – normal

EKG – shown …..


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Case 18 continued – EKG


Case 18: Which of the following increases the risk of sudden

death in this patient?

1) Prior history of syncope

2) Family history of sudden death

3) Frequent runs of non-sustained VT

4) LV wall thickness of >30 mm

5) All of the above


Risk Factors for sudden death in Hypertroprophic Cardiomyopathy

per ACC/ESC Guidelines

Major

Cardiac arrest (VF)Spontaneous sustained VTFamily history of premature

sudden deathUnexplained syncopeLV thickness ≥ 30 mmAbnormal exercise BPNon-sustained VT (Holter)

Possible in Individual Patients

Atrial fibrillationMyocardial ischemiaLV outflow obstructionHigh-risk mutationIntense (competitive) physical

exertion


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Case 19: 51 y.o. male with syncope while waiting for the bus

Otherwise healthy

No PMH

No medications

No family history of sudden death

PE normal

EKG …..


Case 19: EKG


Case 19: Which one of the following is the best next test:

1) Activate the cath lab if within 90 minutes

2) Lytic therapy if cath lab can not be activated within 90 minutes

3) Call the Electrophysiology service

4) Leave me alone, I am getting tired!

5) None of the above


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Brugada Syndrome

Estimated 3-9% of out-of-hospital causes of VF arrest

Heritable disorder of the sodium channel (SCN5A) and makes patients susceptible to polymorphic VT and sudden death

No structural heart disease EKG with ST elevation in precordial leads (V1

and V2) – these changes can be dynamic and associated with RBBB

Patients with Brugada Syndrome who present with syncope have a 2-year risk of sudden cardiac death of 30% ICD is therefore recommended.


Case 20: For which of the following should antibiotic

prophylaxis be recommended?

A. Mitral valve prolapse with no murmur

B. Mitral valve prolapse with a murmur

C. Prior history of endocarditis

D. Bicuspid Aortic valve

E. All of the above


New AHA Recommendations …..

artificial heart valves a history of infective endocarditis certain specific, serious congenital (present from

birth) heart conditions, including: unrepaired or incompletely repaired cyanotic

congenital heart disease, including those with palliative shunts and conduits

a completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first six months after the procedure

any repaired congenital heart defect with residual defect at the site or adjacent to the site of a prosthetic patch or a prosthetic device

a cardiac transplant that develops a problem in a heart valve.


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Case 21: After placement of a drug eluting stent in the right coronary

artery, when should the patient have elective surgery?

A. 6 weeks

B. 3 months

C. 6 months

D. 12 months

E. Neither


What to do with Patients Awaiting Surgery after PCI?

Is there an optimal delay after coronary stenting prior to non-cardiac surgery?

Analysis of the Mayo Clinic PCI and Surgical databases (1990-2000)

207 patients identified who underwent surgery after a successful PCI with Bare Metal Stent

How did they do?

Wilson SH et al JACC 2003;42:234-40

UCSF, Department of Medicine, CME 147Wilson SH et al JACC 2003;42:234-40

Complications of non-cardiac surgery after coronary PCI

It is suggested that postPCI with a BMS, surgery be delayed by 6 weeks

What to do with DES????


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Case 22: Which of the following are contraindications to the placement

of an intra-aortic balloon pump?

A. Severe PVDB. Aortic dissectionC. Aortic aneurysmD. Severe aortic valve regurgitationE. All the above


IABP Pumping

DEFLATES INFLATES

Courtesy of Duy Nguyen, UCSF


Indications for IABP placement

Cardiogenic shock Acute MI Dilated cardiomyopathy with poor cardiac output

Mechanical complications of MI Papillary muscle rupture MR Ventricular Septal Defect (VSD)

Valvular Heart Disease Mitral regurgitation (especially acute MR) Aortic Stenosis complicated by hypotension or

coronary insufficiency Refractory myocardial ischemia

Facilitated revascularization for high-rsik cases


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Case 23: Patient with leg pain with ambulation sees you in clinic.

Ankle-brachial index is ordered and it is 1.4. This reflects that:

A. ABI > 1.0 is normalB. No more vascular testing is required

as the pain is most likely non-vascular given high ABI

C. ABI of > 1.2 is not predictive of risk of future events

D. A and B are correctE. None of the above are correct

ABI =

• Cornerstone of PAD Diagnosis

• Ankle and brachial systolic pressures taken using a hand-held Doppler device

• Supine position

• After 5+ minutes of rest

The Ankle‐Brachial Index

Ankle systolic pressureBrachial systolic pressure

Normal ABI 0.90-1.30

PAD ABI <0.90

Severe PAD ABI <0.40

Non-compressible ABI >1.30

Performance of the ABI Test

TEST SENSITIVITY SPECIFICITY

ABI 95-97% 99-100%

PULSE EXAM (DP)PULSE EXAM (PT)

50%

71%

73%

91%

Ouriel K, et al. Surgery. 1982 Jun;91(6):686-93. Criqui Circ 1985;71:516


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Pulse Volume RecordingsUpper thigh

Lower thigh

Calf

Ankle

Upper thigh

Lower thigh

Calf

Ankle

Pu

lse

Vo

lum

e R

eco

rdin

gs

Iliac/common femoral

SFA/popliteal

Below knee

Limitations of the ABI

• Appropriately trained staff to perform it• ABI correlates poorly with symptoms and functional

limitations• Decreased sensitivity for mild disease or inflow disease

– Exercise ABI critical for patients with suspected PAD and normal resting ABI

• Falsely elevated ABI for patients with “medial calcinosis” or calcified vessels– Diabetes mellitus– Renal failure– Hyperparathyroidism

Do Non‐Compressible Vessels Have any Meaning foa Diabetic? Yes!

Non‐compressible vessels (high ABI) independent predictor of adverse outcome

Significant PAD is generally present though ABI number is not interpretable

Do not consider an ABI > 1.3 “normal”


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Toe‐Brachial Index

Ratio of toe pressure to brachial pressure

Room must be warm to avoid vasoconstriction

Great toe pressure measured using small digit cuff and a flow sensor– Doppler– Strain gauge– Photoplethysmography

Digital vessels almost always compressible

Normal TBI > 0.7

Bonham PA. Nursing. 2003;33:54.

YearMcKenna M, Wolfson S, Kuller L. Atherosclerosis. 1991;87:119-128.

Low ABI: Independent Predictor of Survival

20

30

40

50

60

70

80

90

100

0 2 4 6 8 10

Su

rviv

al (

%)

ABI >0.85

ABI 0.4-0.85

ABI <0.4

N=744 vascular lab patients

ABI and CV Risk

Resnick, et al. Circulation. 2004; 109(6) 733.

ABI

N=4393 American IndiansStrong Heart Study

Optimal ABI?


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ABI Increases CV Risk Prediction Beyond the Framingham Score

• ABI Collaboration. JAMA (2008)

• Meta‐analysis of 16 cohort studies involving 480,325 person‐years of data

– e.g., ARIC, Edinburgh, Framingham offspring, Strong Heart, San Diego, Rotterdam

• Lowest risk of death in ABI 1.11 – 1.4 range

• For each Framingham risk category, low ABI (<.91) doubles CV event and death rate

• ABI adds additive information to Framingham risk score

– Risk reclassification or modification of treatment

• 19% of men

• 36% of women

ABI Collaboration. JAMA. 2008;300:197.

Cardiovascular Disease – Part 1 - UCSF CME · 2013-07-02 · 1 UCSF Internal Medicine Board...

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Transcript of Cardiovascular Disease – Part 1 - UCSF CME · 2013-07-02 · 1 UCSF Internal Medicine Board...