ACS and Heart FailureJonathon Firnhaber, MD, FAAFP

Associate Professor

The Brody School of Medicine at East Carolina University

Greenville, North Carolina

Learning Objectives

• Establish the diagnosis and therapy of acute coronary syndrome.

• Formulate the indications for fibrinolysis, glycoprotein llb/lIla agents, and angioplasty in acute coronary syndrome.

• Analyze the difference between systolic and diastolic cardiac dysfunction.

• Differentiate the therapies that increase the chance for survival in patients with heart failure and those that only improve symptoms.

• Review the role of neurohormonal activation in systolic heart failure.

Acute Coronary Syndrome

• Acute coronary syndrome– Unstable angina (UA)

– Non-ST-elevation myocardial infarction (NSTEMI)

– ST-elevation myocardial infarction (STEMI)

1. A 52-year-old man presents to the ED with a 45-minute history of squeezing substernal chest pressure radiating to his left arm.

An ECG from a routine physical two months ago was normal.

Question 1 ECG1. This patient’s history and ECG are most consistent with which one of the following?

A. Esophageal spasm

B. Acute ST segment elevation MI (STEMI)

C. Acute non-ST segment elevation MI (NSTEMI)

D. Pericarditis

ACS and Heart Failure

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1. This patient’s history and ECG are most consistent with which one of the following?

A. Esophageal spasm

B. Acute ST segment elevation MI (STEMI)

C. Acute non-ST segment elevation MI (NSTEMI)

D. Pericarditis6%

1%

36%

60%

ECG Findings: ST Segment Depression, Inferior and Lateral Precordial Leads

Acute Coronary Syndrome

• UA and NSTEMI are closely related, with similar presentations, but with differing severity:– Both cause ST-segment depression or prominent T-

wave inversion– Ischemia severe enough to cause myocardial injury

with release of biomarkers (troponin I, troponin T, CK-MB) = NSTEMI

• STEMI is distinguished from UA/NSTEMI by presence of ST-segment elevation on EKG (followed by Q wave)– Warrants immediate reperfusion therapy

Acute Coronary Syndrome

• Etiology: reduced myocardial perfusion– Reduced O2 supply (more common)

– Increased O2 demand

Acute Coronary Syndrome

• Most commonly due to occlusive thrombus developing on top of a disrupted atherosclerotic plaque– Nearly 50% at sites with < 50% luminal narrowing

• Other etiologies: – Spasm at site of atherosclerotic plaque– Normal coronary arteries with spasm

• Prinzmetal’s angina; transient ST elevation associated

– Arterial inflammation (Kawasaki disease)– Cocaine-induced (treat with NTG and CCB)

2. This patient’s initial troponin is normal. Which of the following statements about cardiac biomarkers is correct?

A. A single negative troponin excludes MI

B. Troponin is a better marker of reinfarction than is CK-MB

C. Myoglobin can be detected as early as 2 hours after the onset of myocardial necrosis

D. CK-MB and myoglobin rise and fall more slowly than troponin

ACS and Heart Failure

© American Academy of Family Physicians. All Rights Reserved.

2. This patient’s initial troponin is normal. Which of the following statements about cardiac biomarkers is correct?

A. A single negative troponin excludes MI

B. Troponin is a better marker of reinfarction than is CK-MB

C. Myoglobin can be detected as early as 2 hours after the onset of myocardial necrosis

D. CK-MB and myoglobin rise and fall more slowly than troponin

44%

1%

25%

31%

Troponin

• Troponin is the biomarker of choice in the evaluation of ACS. Troponin I and T are equivalent.

• Detected 3-6 hours after the onset of ischemic symptoms

• Normal serial troponin levels exclude myocardial infarction, but do not exclude unstable angina.

• Troponin remains elevated for 7-14 days post-MI

Myoglobin

• Earliest marker of MI– released from damaged muscle more rapidly than

CK-MB or troponin– can be detected as early as 2 hours after cardiac

necrosis– Peaks at about 8 hours; remains elevated < 24

hours• Sensitive but not specific.

– Cardiac origin must be confirmed with a more cardiac-specific enzyme

– false positives due to skeletal muscle injury

CK-MB

• Remains elevated for 36-48 hours following MI

• Early peak (12-18 hours) suggests reperfusion

• CK-MB and myoglobin rise and fall more rapidly than troponin

– better for diagnosing reinfarction

3. This patient continues to have pain despite treatment with IV NTG, morphine, ß-blocker, aspirin and heparin. A repeat ECG shows persistent ST segment depression. What is the next most appropriate intervention?

A. Emergency PCI (percutaneous coronary intervention)

B. Fibrinolysis

C. Emergency CABG

D. Glycoprotein IIb/IIIa agent

3. This patient continues to have pain despite treatment with IV NTG, morphine, ß-blocker, aspirin and heparin. A repeat ECG shows persistent ST segment depression. What is the next most appropriate intervention?

A. Emergency PCI (percutaneous coronary intervention)

B. Fibrinolysis

C. Emergency CABG

D. Glycoprotein IIb/IIIa agent12%

81%

6%

1%

ACS and Heart Failure

© American Academy of Family Physicians. All Rights Reserved.

2007 ACC/AHA UA/NSTEMI Guideline Revision

• Recommends initial invasive strategy in patients with the following characteristics:– Recurrent angina or ischemia at rest or with low-

level activities despite intensive medical therapy

– Elevated cardiac biomarkers (TnT or TnI)

– New or presumably new ST-segment depression

– Signs or symptoms of HF or new or worsening mitral regurgitation

– High-risk findings from noninvasive testing

2007 ACC/AHA UA/NSTEMI Guideline Revision

• Recommends initial invasive strategy in patients with the following characteristics:– Hemodynamic instability

– Sustained ventricular tachycardia

– PCI within 6 months

– Prior CABG

– High risk score (e.g., TIMI, GRACE)

– Reduced left ventricular function (LVEF less than 40%)

ACS Therapy: Fibrinolysis

• Fibrinolytic therapy or primary percutaneous coronary intervention (PCI) should be strongly considered in all STEMI patients with a symptom onset within 12 hours– tPA or reteplase (Retavase): heparin is given to

increase the likelihood of patency in the infarct-related artery

– Streptokinase or APSAC: heparin does not offer any additional benefit

ACS Therapy: Glycoprotein IIb/IIIa Inhibition

• Glycoprotein IIb/IIIa receptor blockers– Inhibit platelet aggregation

– Tirofiban (Aggrastat), Eptifibatide (Integrilin)• Further reduce the incidence of ischemic events in

patients with NSTEMI, when administered with heparin and aspirin

– Abciximab (ReoPro)• Reduces the risk of closure after angioplasty

ACS Therapy: PCI with Stent

• Bare metal– Bare metal acts as foreign body, increasing risk of in-

stent thrombosis – clopidogrel + ASA decreases risk; continue 1 month post-stent if no MI (or 12 months if post-MI)

– Epithelialization may progress to in-stent stenosis

• Drug-eluting– Delay epithelialization, maintaining bare metal longer;

continue clopidogrel + ASA for 12 months– Sirolimus (Cypher), Tacrolimus (Mahoroba), Paclitaxel

(Taxus)

ACS Therapy: Emergency CABG

• Considered only if coronary anatomy is not suitable for PCI

ACS and Heart Failure

© American Academy of Family Physicians. All Rights Reserved.

4. A 70-year-old woman with history of hypertension and type 2 diabetes presents to the ED with a 14-hour history of profound shortness of breath, but no chest pain.

Her current medications include HCTZ, lisinopril and insulin.

Question 4 ECG

4. This patient’s history and ECG are most consistent with which one of the following?

A. Unstable angina

B. Acute anterior wall ST segment elevation myocardial infarction

C. Pericarditis

D. Acute anterior wall ischemia

4. This patient’s history and ECG are most consistent with which one of the following?

A. Unstable angina

B. Acute anterior wall ST segment elevation myocardial infarction

C. Pericarditis

D. Acute anterior wall ischemia7%

0%

91%

4%

ECG FindingsQ waves and ST segment elevation with T-wave

inversion, anterior precordial leads (V2 – V5)ACS: STEMI

ST segments:• Elevation occurs immediately post plaque-rupture and

is consistent with myocardial injury.• Resolution of ST elevation suggests reperfusion.• Persistent ST elevation may be seen with aneurysm

formation.• ST depression indicates myocardial ischemia.

Q waves:• Develop approximately 12 hours post plaque-rupture,

and are indicative of (electrically) dead myocardium (MI).

• Typically permanent.

ACS and Heart Failure

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ACS: STEMI

• Anterior/Anteroseptal– LAD– Leads V1 – V4

• Lateral– Circumflex– Leads V5 – V6

• Inferior– RCA– Leads II, III, aVF

5. Which of the following medications improves survival post-MI?

A. Digoxin

B. Dihydropyridine calcium-channel blocker

C. Long-acting nitrate

D. ACE-inhibitor

5. Which of the following medications improves survival post-MI?

A. Digoxin

B. Dihydropyridine calcium-channel blocker

C. Long-acting nitrate

D. ACE-inhibitor89%

2%

4%

5%

Post-MI Survival

• ACE-inhibitors, ß-blockers, statins and ASA improve survival post MI.

• Nitrates, clopidogrel, calcium-channel blockers and digoxin may improve symptoms, but do not affect survival.

6. Which one of the following statements regarding systolic heart failure is correct?

A. Left ventricular ejection fraction is < 40%.

B. Systolic dysfunction produces different symptoms than diastolic dysfunction.

C. Systolic dysfunction results from increased ventricular stiffness.

D. Systolic dysfunction and diastolic dysfunction do not coexist in the same patient.

6. Which one of the following statements regarding systolic heart failure is correct?

A. Left ventricular ejection fraction is < 40%.

B. Systolic dysfunction produces different symptoms than diastolic dysfunction.

C. Systolic dysfunction results from increased ventricular stiffness.

D. Systolic dysfunction and diastolic dysfunction do not coexist in the same patient.

1%

57%

29%

14%

ACS and Heart Failure

© American Academy of Family Physicians. All Rights Reserved.

Systolic Heart Failure

• Systolic dysfunction: ejection fraction < 40%• Systolic dysfunction may produce the same

symptoms as diastolic dysfunction.• Diastolic dysfunction results from increased

ventricular stiffness and decreased ventricular compliance.

• Both systolic and diastolic dysfunction may be present in the same patient.

Systolic Heart Failure Treatment

Low cardiac output triggers neurohormonal activation, which ultimately results in premature apoptosis of cardiac myocytes.

• Preload reduction– Diuretics, nitrates

• Afterload reduction– ACEI, ARB, hydralazine, nitrates

• Sympathetic blockade– ß-blockers

• Aldosterone-antagonist therapy– Spironolactone, eplerenone (Inspra)

7. Which one of the following is considered a contraindication to the use of ß-blockers for congestive heart failure?

A. Mild asthma

B. Symptomatic heart block

C. New York Heart Association (NYHA) Class III heart failure

D. NYHA Class I heart failure in a patient with a history of a previous myocardial infarction

E. An ejection fraction <30%

7. Which one of the following is considered a contraindication to the use of ß-blockers for congestive heart failure?

A. Mild asthma

B. Symptomatic heart block

C. New York Heart Association (NYHA) Class III heart failure

D. NYHA Class I heart failure in a patient with a history of a previous myocardial infarction

E. An ejection fraction <30%

0%

4%

86%

3%

7%

ß-blockers and Heart Failure

• Mortality rates are improved in HF patients who receive ß-blockers in addition to diuretics and ACEIs.

• ß-blockers are effective in patients with NYHA Class II or III heart failure.

• There is no absolute threshold ejection fraction.

• ß-blockers decrease mortality in patients with prior MI, regardless of NYHA classification

ß-blockers and Heart Failure

• Contraindications to ß-blocker use include:– Hemodynamic instability

– Heart block

– Bradycardia

– Severe asthma

• ß-blockers may be initiated in patients with mild asthma or COPD, as long as they are monitored for potential interactions

ACS and Heart Failure

© American Academy of Family Physicians. All Rights Reserved.

ß-blockers and Heart Failure

• ß-blockers should be started when the patient is stable and euvolemic.

• ß-blocker benefit is a drug-specific effect, not a class effect. Proven ß-blockers include:– Metoprolol succinate– Carvedilol– Bisoprolol

8. Which one of the following is preferred for chronic treatment of congestive heart failure due to left ventricular systolic dysfunction?

A. Diuretics

B. Digoxin

C. Calcium channel blockers

D. ACE inhibitors

E. Hydralazine plus isosorbide dinitrate

8. Which one of the following is preferred for chronic treatment of congestive heart failure due to left ventricular systolic dysfunction?

A. Diuretics

B. Digoxin

C. Calcium channel blockers

D. ACE inhibitors

E. Hydralazine plus isosorbide dinitrate

76%

9%

10%

3%

4%

ACE-Inhibitors and Heart Failure

• ACEIs are preferred for CHF due to LV systolic dysfunction because they offer the greatest reduction in mortality.

Other Treatments for Heart Failure

• Hydralazine/isosorbide is a reasonable alternative.

• Diuretics typically should not be used as monotherapy.

• Digoxin may help with symptoms and decreases hospitalizations, but has not been proven to affect mortality. Aim for a serum level of <1.0 ng/mL

9. A 70-year-old woman with hypertension presents with progressive dyspnea. Rales at the lung bases are noted, and chest x-ray shows pulmonary edema with a normal size heart. Which of the following statements is true?

A. Viral cardiomyopathy presents with diastolic dysfunction.

B. Treatment of diastolic heart failure requires high-dose diuretics.

C. The ejection fraction with diastolic heart failure is > 40%.

D. Digoxin therapy should be considered in the majority of patients with diastolic heart failure.

ACS and Heart Failure

© American Academy of Family Physicians. All Rights Reserved.

9. A 70-year-old woman with hypertension presents with progressive dyspnea. Rales at the lung bases are noted, and chest x-ray shows pulmonary edema with a normal size heart. Which of the following statements is true?

A. Viral cardiomyopathy presents with diastolic dysfunction.

B. Treatment of diastolic heart failure requires high-dose diuretics.

C. The ejection fraction with diastolic heart failure is > 40%.

D. Digoxin therapy should be considered in the majority of patients with diastolic heart failure.

6%

6%

19%

70%

Diastolic Heart Failure

• RCTs specifically evaluating therapy for diastolic heart failure are limited.

• Patients tend to be volume sensitive and can develop hypotension with excessive diuresis.

• If rapid atrial fibrillation/flutter is present, digoxin is indicated for rate control.

• Careful preload reduction is appropriate.• Careful decrease in heart rate, using ß-blocker

or non-dihydropyridine CCB is appropriate.

10. A 56-year-old male with longstanding hypertension and a 30-pack-year smoking history has a 2-day history of dyspnea on exertion. Physical examination is only notable for rare crackles at the bases. Which one of the following serologic tests would be most helpful for detecting left ventricular dysfunction?

A. Brain-natriuretic peptide (BNP)

B. Troponin-T

C. C-reactive protein

D. D-dimer

E. Cardiac interleukin-2

10. A 56-year-old male with longstanding hypertension and a 30-pack-year smoking history has a 2-day history of dyspnea on exertion. Physical examination is only notable for rare crackles at the bases. Which one of the following serologic tests would be most helpful for detecting left ventricular dysfunction?

A. Brain-natriuretic peptide (BNP)

B. Troponin-T

C. C-reactive protein

D. D-dimer

E. Cardiac interleukin-2

1%

98%

0%

0%

2%

BNP and Heart Failure

• BNP is secreted from the ventricles in response to ventricular volume expansion and pressure overload.

• Release is directly proportional to ventricular dysfunction and correlates with end-diastolic pressure.

• BNP undergoes partial renal excretion; levels are inversely proportional to creatinine clearance.

BNP and Heart Failure

• BNP < 100 excludes CHF as a cause of dyspnea

• BNP > 400 confers a 95% likelihood of CHF

• BNP 100 – 400 requires further investigation– Pulmonary disorders that can elevate BNP include

lung cancer, cor pulmonale and pulmonary embolus– Other causes of BNP elevation include cirrhosis with

ascites, primary hyperaldosteronism, Cushing disease

– These disorders do not cause the same extent of BNP elevation as LV dysfunction

ACS and Heart Failure

© American Academy of Family Physicians. All Rights Reserved.

References: ACS / Heart Failure• ACC/AHA 2007 Guidelines for the Management of Patients With

Unstable Angina/Non–ST-Elevation Myocardial Infarction: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction) Circulation 2007;116;803-877.

• Braunwald E, Antman EM, Beasley JW, et al: ACC/AHA 2002 Guideline Update for the Management of Patients with Unstable Angina and Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Committee on the Management of Patients with Unstable Angina. American College of Cardiology/American Heart Association, 2002, pp 6-7.

References: ACS / Heart Failure• Krishnaswamy P, Lubien E, Clopton P, et al: Utility of beta-

natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic function. Am J Med 2001;111(4):274-279.

• Maisel AS, Mehra MR: Understanding B-type natriuretic peptide and its role in diagnosing and monitoring congestive heart failure. Clin Cornerstone 2005;7(Suppl 1):S7-S17.

• Jeremias A, Gibson M. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med. 2005; 142(9): 786-91.

• Miller CD, Roe MT, Mulgard J, et al. Impact of acute beta-blocker therapy for patients with non-ST-segment elevation myocardial infarction. Am J Med. 2007;120:685-692.

References: ACS / Heart Failure• Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of

carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362:7-13.

• Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol. 2007;50(25):2357-2368.

• Wu AH, Jaffe AS, Apple FS et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines: use of cardiac troponin and B-type natriuretic peptide or N-terminal proB-type natriuretic peptide for etiologies other than acute coronary syndromes and heart failure. Clin Chem. 2007;1;53(12):2086-96.

• Hunt SA, American College of Cardiology, et al. ACC/AHA 2005 guidelines update for the diagnosis and management of chronic heart failure in the adult. J Am Coll Cardiol. 2005; 46(6):e1-82.

Answers1. C2. C3. A4. B5. D6. A7. B8. D9. C10.A

ACS and Heart Failure

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