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Cardiogenic Shock, Acute Coronary Syndromes and Heart Failure

Fredric Ginsberg, M.D.

Joseph Parrillo, M.D.

Slide 2

Cardiogenic Shock

• Inadequate tissue perfusion resulting from cardiac dysfunction • Clinical definition: decreased cardiac output and tissue hypoxia in the presence of adequate intravascular volume • Hemodynamic definition: Sustained systolic BP<90 mmHg, cardiac index <2.2 L/min/m2, PCWP > 15 mm Hg

Parrillo, J. 2005

Slide 3

Causes of Cardiogenic Shock

• Acute MI – Pump failure – Mechanical complications – Right ventricular infarction • Other conditions – End-stage cardiomyopathy – Myocarditis (Fulminant Myocarditis) – Myocardial contusion – Prolonged cardiopulmonary bypass – Septic shock with myocardial depression – Valvular disease – Stress cardiomyopathy Slide 4

CARDIOGENIC SHOCK Evolution of the Disease

•

Frequently, shock develops after presentation for myocardial infarction.

SHOCK Registry • At presentation 25% in shock • Within 24 hours 75% (median delay = 7 hours) GUSTO Trial • At presentation • After admission 11% in shock 89% Slide 5 SHOCK Registry, Circulation 1995;91:873-81 GUSTO J Amer Coll Cardiol 1995;26:668-74

Schematic Diagram of Stunned Myocardium

Clamp Wall motion abnormality Coronary occlusion Wall motion abnormality during occlusion Coronary reperfusion Return of function Persistent wall motion abnormality (despite reperfusion and viable myocytes) Gradual return of function (hours to days)

From Kloner, R.A., Am J Med 1986;86:14.

Slide 6

Hibernating Myocardium

Wall motion abnormality Atherosclerotic narrowing Wall motion abnormality due to chronic ischemia without infarction From Kloner, R.A.,

Am J Med

1986;86:14.

Slide 7

Cell death

Ischemic Myocardium

Reperfusion Significant residual stenosis Segments with myocardial stunning Segments with both stunning and hibernation Segments with hibernating myocardium No return of function Inotropic support Return of myocardial function Slide 8 Relief of ischemia

Initial Approach: Management

• Assure Oxygenation – Intubation and ventilation if needed • Venous access • Pain relief • Continuous EKG monitoring • Hemodynamic support – Fluid challenge if no pulmonary edema – Vasopressors for hypotension • Dopamine • Norepinephrine Slide 9

Intra-Aortic Balloon Counterpulsation

• Reduces afterload and augments diastolic perfusion pressure • Beneficial effects occur without increase in oxygen demand • No improvement in blood flow distal to critical coronary stenosis • No improvement in survival when used alone • May be essential support mechanism to allow for definitive therapy Slide 10

Revascularization in Acute Myocardial Infarction

Early revacularization in Acute Myocardial Infarction complicated by cardiogenic shock 1.0

Overall 30-Day Survival in the Study

0.8

Revascularization (n=152) Survival = 53%

0.6

0.4

Medical therapy (n=150) Survival = 44%

0.2

0.

0 0 Hochman, J.S., et al,

N Engl J Med

1999;341:625-34.

5 10 15

p =0.11

20

Days after Randomization

25 30 Slide 11

100

SHOCK Trial Mortality

80

%

60 P = 0.11

46.7

56 P = 0.027

50.3

63.1

P < 0.03

66.4

54.3

40 Revasc Med Rx 20 0 30 days 6 months

Slide 12

1 year

ACC/AHA Class I Indication

• Patients with ST segment elevation MI who have cardiogenic shock and are less than 75 years of age should be brought immediately or secondarily transferred to facilities capable of cardiac catheterization and rapid revascularization (PCI or CABG) if it can be performed within 36 hours of onset of shock. (Level of Evidence: A) Slide 13

National Registry of MI

• National Registry of MI early Revascularization is Underutilized in Cardiogenic Shock – Despite ACC/AHA recommendation to treat patients <75 years of age aggressively with early mechanical revascularization, – In 2001, 2 years after the guidelines were published, only 41% of patients with cardiogenic shock complicating AMI were treated with primary PTCA and only 3.1% underwent early CABG.

– These data demonstrate significant underutilization of guideline recommended therapy.

Babaev A et al Circ 2002 106(19):1811 (abstract)

Slide 14

Pathophysiology of Cardiogenic Shock

• The following are observations from the SHOCK Trial and Registry that Challenge the Classic Paradigm – LVEF is only moderately depressed (30%), with a wide range of EFs and LV sizes noted.

– Systemic vascular resistance (SVR) on vasopressors is not elevated (~ 1350), with a very wide range of SVRs measured.

– A clinically evident systemic inflammatory response syndrome is often present in patients with CS.

– Most survivors (85%) have NYHA functional Class I-II CHF status.

Hochman JS. Circ .2003;107:2998-3002.

Slide 15

Overproduction of Nitric Oxide The Overproduction of Nitric Oxide May Cause Both Myocardial Depression and Inappropriate Vasodilatation.

Thus, excess nitric oxide and peroxy nitrites may be a major contributor to cardiogenic shock complicating MI.

Slide 16 Cotter, Eur Heart J. 2003:24:1287-1295

Acute Coronary Syndromes: Definitions

Acute coronary syndrome

:

Constellation of clinical symptoms compatible with acute myocardial ischemia 1. ST-segment elevation MI (STEMI) 2. Non-ST-segment elevation MI (NSTEMI) 3. Unstable angina Braunwald. Circulation 2002; 106:1893-2000.

www.acc.org/clinical/guidelines/unstable/unstable.pdf

Unstable angina:

1.angina at rest (usually >20 minutes) 2.new-onset of class III or IV angina 3.increasing angina (from class I or II to III or IV) Slide 17

Hospitalizations in the US Due to Acute Coronary Syndromes

Acute Coronary Syndromes ~1.8 Million Hospital Admissions

UA/NSTEMI

1.42 Million

STEMI

0.41 Million Admissions Admissions Per Year Per Year National Hospital discharge survey 1999. National Center for health Statistics/Centers for Disease Control and Prevention. Series 13, No. 14. September 20000. Slide 18

Pathogenesis of Acute Coronary Syndromes

White HD. Am J Cardiol 1997;80 (4A):2B-10B.

Plaque rupture Platelet adhesion Platelet activation Partially occlusive arterial thrombosis & unstable angina Microembolization & non-ST-segment elevation MI Totally occlusive arterial thrombosis & ST-segment elevation MI

Slide 19

Structure of Thrombus Following Plaque Disruption

UA/NSTEMI: Partially-occlusive thrombus (primarily platelets) STEMI: Occlusive thrombus (platelets, red blood cells, and fibrin)

Intra-plaque Plaque core thrombus (platelet-dominated) Intra-plaque thrombus Plaque core (platelet-dominated)

UA = Unstable Angina NSTEMI = Non-ST-segment Elevation Myocardial Infarction STEMI = ST-segment Elevation Myocardial Infarction SUDDEN DEATH

White HD.

Am J Cardiol

1997;80 (4A):2B-10B.

Slide 20

Diagnostic Algorithm

&/or + T roponin or + CK-MB

ST-segment elevation MI Non-ST Elevation ACS* Non-ST Elevation MI Therapeutic goal: rapidly break apart fibrin mesh to quickly restore blood flow Consider fibrinolytic therapy, if indicated, or primary percutaneous coronary intervention (PCI) Therapeutic goal: prevent progression to complete occlusion of coronary artery and resultant MI or death Consider GP IIb-IIIa inhibitor + aspirin + heparin before early diagnostic catheterization Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf

.

Slide 21

Risk of MI & Death During Treatment

The following graph displays the risk of MI and death during treatment with low-dose aspirin and iv heparin in men with unstable cad

Wallentin LC, et al. J Am Coll Cardiol, 1991;18:1587-93.

0.25

Placebo 0.20

0.15

0.10

0.05

0.00

0 3 Aspirin 75 mg Risk ratio 0.52

95% CL 0.37 - 0.72

6 Months

Slide 22

9 12

Low Molecular Weight Heparin (LMWH) vs. Unfractionated Heparin (UFH)

The following chart displays the low molecular weight heparin (LMWH) vs. unfractionated heparin (Ufh) in non-st elevation ACS: effect on death, MI, recurrent ischemia.

Trial:

Braunwald. Circulation. 2002;106:1893-2000.

www.acc.org/clinical/guidelines/unstable/unstable.pdf



Day: 6 FRIC

(Dalteparin; n = 1,482) 

14 FRAXIS

(nadroparin; n = 2,357) 

(p= 0.032) 14 ESSENCE

(enoxaparin; n = 3,171) 

(p= 0.029) 14 TIMI 11B

(enoxaparin; n = 3,910)

.75

LMWH Better 1.0

UFH Better 1.5

Slide 23

Effects of Clopidogrel

This graph demonstrates the effects of Clopidogrel in addition to Aspirin in patients with ACS without ST-Segment Elevation

14 % 12 10 Placebo + ASA 11.4

% 9.3% 8 6 4 2 0 0

N Engl J Med. 2001;345:494 502.

3 6 Months of Follow-Up

Slide 24

Clopidogre + ASA 9 l 20% RRR P < 0.001

12 N = 12,562

Hospital Care Anti-Thrombotic Therapy

I IIa IIb III

Immediate aspirin Clopidogrel,if ASA contraindicated Aspirin + Clopidogrel, for up to 1 month, if medical therapy or PCI is planned Heparin (IV unfractionated, LMW) with antiplatelet agents listed above Enoxaparin preferred over UFH unless CABG is planned within 24 hours Braunwald. Circulation 2002;106:1893-2000.

www.acc.org/clinical/guidelines/unstable/unstable.pdf

Slide 25

Hospital Care Platelet GP IIb/IIIa Inhibitors (1)

I IIa IIb III

Any GP IIb/IIIa inhibitor + ASA/Heparin for all patients, if cath/PCI planned Eptifibatide or tirofiban + ASA / Heparin for high risk * patients in whom early cath/PCI is not planned. Any GP IIb/IIIa inhibitor for patients already on ASA + Heparin + clopidogrel, if cath/PCI is planned Braunwald. Circulation 2002;106:1893-2000.

www.acc.org/clinical/guidelines/unstable/unstable.pdf

Slide 26

Hospital Care Platelet GP IIb/IIIa Inhibitors (2)

I IIa IIb III

Eptifibatide or tirofiban + ASA / Heparin for patients without continuing ischemia in whom PCI is not planned.

Abciximab for patients in whom PCI is not planned.

Braunwald. Circulation 2002;106:1893-2000.

www.acc.org/clinical/guidelines/unstable/unstable.pdf

Slide 27

Hospital Care Anti-ischemic Therapy (1)

I IIa IIb III

β -blocker (IV ► oral) if not contraindicated Non-dihydropyridine Ca2+ antagonist if β blocker contraindicated and no LV dysfunction, for reccurrent ischemia ACE inhibitor if blocker , ↑ BP persists with NTG+ β – for patients with CHF or diabetes.

Braunwald. Circulation 2002;106:1893-2000.

www.acc.org/clinical/guidelines/unstable/unstable.pdf

Slide 28

Hospital Care Anti-Ischemic Therapy (2)

I IIa IIb III

ACE inhibitor for all ACS pts Extended-release CA2+ blocker instead of β blocker Immediate-release Ca2+ blocker with β blocker

C

Long-acting Ca2+ blocker for recurrent ischemia, if no contraindications and NTG + β-blocker used fully Braunwald. Circulation 2002;106:1893-2000.

www.acc.org/clinical/guidelines/unstable/unstable.pdf

Slide 29

10% 8%

ST-segment Depression Predicts Higher Risk of Mortality in ACS

% Cumulative Mortality at 6 Months ST-segment depression 8.9% ST-segment elevation 6.8%

6% 4%

T-wave inversion 3.4%

2% 30 60 90 Savonitto S.

J Am Med Assoc

1999; 281: 707-711.

120

Days from randomization

Slide 30 150 180

Mortality Rates According to Level of Cardiac Troponin

Slide 31

Variables Used in the TIMI Risk Score

• Age >65 years • At least 3 risk factors for CAD • Known prior coronary stenosis of >50% • ST segment deviation on presenting ECG • At least 2 anginal events in prior 24 hours • Use of aspirin in prior 7 days • Elevated serum cardiac biomarkers Slide 32

Number of TIMI Risk Factors Predicts Short-Term Recurrent Events

Slide 33

TIMI UA Risk Score: Primary Endpoint at 6 mos

35 30 25 20 15 10 5 0

CONS 11.8

12.8

INV OR=0.75

CI (0.57, 1.00) 20.3

16.1

OR=0.55

CI (0.33, 0.91) 30.6

19.5

% of Pts:

Low 0-2

25%

Intermed. 3-4

60%

High 5-7

15%

Slide 34

Troponin and ST-Segment Shift Predict Benefit of Invasive Treatment Strategy

Cannon. J Invas Cardiol 2003; 15:22B Slide 35

• • •

Management of Patients with Unstable Angina

ACC/AHA Guideline Update for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation MI Class I An early invasive strategy in patients with a high-risk indicator: – Recurrent angina/ischemia despite intensive anti-ischemic rx – Elevated troponin-T or troponin-I – New or presumably new ST-segment depression – Recurrent angina/ischemia with CHF sx, S3, pulmonary edema, worsening rales, or new or worsening MR – High-risk findings on noninvasive stress testing – Depressed LV systolic function (EF <40%) – Hemodynamic instability – Sustained ventricular tachycardia – PCI within 6 months – Prior CABG Braunwald, Circulation. 2002:106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pd

Either early invasive or early conservative strategy if not high risk Slide 36

2002 ACC/AHA Guidelines for the Management of High-risk NSTE ACS

At presentation ST-segment depression &/or elevated cardiac troponin Need to immediately arrest thrombus progression Need to eliminate occlusive ruptured plaque



Aspirin

 

Heparin or low-molecular-weight heparin GP IIb-IIIa inhibitor Start immediate Send for catheterization & revascularization within 24-48 hours Cautionary information

  

No clopidogrel within 5-7 days prior to CABG surgery No enoxaparin within 24 hours prior to CABG surgery No abciximab, if PCI is not planned

Adapted from Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf

.

Slide 37

Ongoing Evaluation in an Early Conservative Strategy

Early medical management Recurrent Symptoms/ischemia Heart failure Serious arrhythmia Evaluate LV function EF < .40

EF  .40

Patient stabilizes

Braunwald E, et al. 2002.

http://www.acc.org/clinical/guidelines/unstable/unstable.pdf

.

Not low risk Stress Test Low risk Immediate angiography Slide 38 Follow on Medical Rx

Guideline Update

• ACC/AHA Guideline Update for the Management of Patients with Unstable Angina and on-ST-Segment Elevation MI - Class I indications for revascularization with PCI or CABG • CABG for > 50% stenosis of the left main coronary artery • CABG for 3 vessel CAD • CABG for 2 vessel CAD including proximal LAD stensoes & EF < 50% • PCI or CABG for 1 or 2 vessel CAD, no proximal LAD large area of viability, high-risk noninvasive test • PCI for patients with multivessel CAD, normal EF, no diabetes • IV platelet GP IIb/IIIa inhibitior in ACS patients undergoing PCI Braunwald, Circulation. 2002:106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pd

Slide 39

Guideline Update

• ACC/AHA Guideline Update for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation MI Class IIa indications for revascularization with PCI or CABG • Repeat CABG for patients with multiple saphenous vein graft stenoses especially if LAD graft • PCI for focal saphenous vein graft lesions or multiple lesions if poor surgical candidate • PCI or CABG for patients with 1 or 2 vessel CAD, not proximal LAD, but moderate area of viability and ischemia • PCI or CABG for patients with 1 vessel CAD with proximal LAD • CABG with Internal Mammary artery for patients with multivessel CAD and diabetes Braunwald, Circulation. 2002:106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pd

Slide 40

Recommendations for Revascularization

Braunwald, Circulation. 2002:106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pd

Slide 41

ACC/AHA REVISED GUIDELINES

Braunwald E, et al. Circ. 2002;106:1893.

UA/NSTEMI



ASA, Heparin/Enox.,



block., Nitrates, Clopidogrel



RISK STRATIFY High Risk * Low Risk * Recurrent ischemia; Trop; ST; LV failure/dysf.;

hemodynamic instability; VT; prior CABG



Enoxeparin. Preferred to UFH (IIa)



If coronary arteriography >24 hours

Slide 42

ACC/AHA REVISED GUIDELINES

Braunwald E, et al. Circ. 2002;106:1893.

High Risk Cor. Arteriography LMCD, 3VD+LV Dys., or Diab. Mell.

1 or 2VD, Suitable for PCI CABG Clopidogrel, IIb/IIIa inhib.

PCI Normal Consider Alternative Diagnosis Discharge on ASA, Clopidogrel, Statin, ACEI

Braunwald E, et al.

Discharge Medications

I IIa IIb III

ASA, if not contraindicated Clopidogrel, when ASA contraindicated Aspirin + Clopidogrel, for up to 9 months  -blocker, if not contraindicated Lipid  agents (statins) + diet ACE Inhibitor: CHF, EF < 40%, DM, or HTN Braunwald, Circulation. 2002:106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pd

Braunwald. Circulation 2002;106:1893-2000.

Slide 44

Death or Major Cardiovascular Events

This graph displays the all-cause death or major cardiovascular events in all randomized subjects Slide 45

Reductions in Major Cardiac End Points

Cannon CP, et al N Engl J Med. 2004:350:1495-1504 Slide 46

Risk Factor Modification

Braunwald, Circulation. 2002:106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pd

Slide 47

Heart Failure due to LV Systolic Dysfunction

• Approximately 5 million Americans have Heart Failure (male to female ratio 1:1) • 550,000 new cases annually • Hospital discharges 1,000,000 annually • 80% of men and 70% of women under the age of 65 with HF will die within 8 years Numbers based on 2000 data.

American Heart Association.

2003 Heart and Stroke Statistical Update

. Dallas, Tex: AHA; 2002.

Slide 48

Neurohormonal Activation in Heart Failure

Myocardial injury to the heart (CAD, HTN, CMP, Valvular disease) Initial fall in LV performance,  wall stress Remodeling and progressive worsening of LV function

Activation of RAS and SNS

Fibrosis, apoptosis, hypertrophy, cellular/ molecular alterations, myotoxicity Peripheral vasoconstriction Hemodynamic alterations Morbidity and mortality Arrhythmias Pump failure Slide 49 RAS, renin-angiotensin system; SNS, sympathetic nervous system.

Heart failure symptoms

F

atigue

A

ctivity altered

C

hest congestion

E

dema

S

hortness of breath

LV Remodeling After Anteroseptal MI

1 week 3 months

EDV 137 mL ESV 80 mL EF 41% EDV 189 mL ESV 146 mL EF 23%

Apical 4 Chamber View

Slide 50

Drugs for Heart Failure

• ACE-inhibitors • Beta-blockers • Angiotensin receptor blockers • Aldosterone antagonists • Loop diuretics • Nitrates with hydralazine • Digoxin • Nesiritide, inotropic agents Slide 51

ACE-Inhibition and CHF Trials

• SAVE--captopril, 1992. Post-MI (not CHF) with EF<40%, f/u 42 mos, 2231 pts. Mortality reduced from 25% to 20% NEJM 1992;327:669 • SOLVD--enalapril, 1991. CHF pts, class II-III, EF<35%, f/u 41 mos, 2569pts. Mortality reduced from 39% to 35% NEJM 1991;325:293 • SOLVD--enalapril, 1992. Asymptomatic LV dysfunction, EF<35%, f/u 37 mos, 4228 pts Non-significant reduction in mortality, significant reduction in CHF and hospitalization NEJM 1992;327:685 Slide 52

ACE-I and CHF: Meta-analysis

• Captopril, enalapril, ramipril, quinapril, lisinopril • 32 trials, 7105 patients, FC II-III • 2 mortality trials • Combined: total mortality reduced 21.9% to 15.8% and total mortality plus CHF hosp reduced 32.6% to 22.4% • Summary: – 1. Improvement in risk of death or MI or CHF hospitalization – 2. Class effect • JAMA. 1995. 273:1450 Slide 53

Beta Blockade-Rationale

• Catecholamine levels are increased in CHF • Higher levels correlate with more severe disease • Catecholamines contribute to myocyte hypertrophy and necrosis (apoptosis) • More ischemia, arrhythmia, vasoconstriction and LV dilatation Slide 54

Metoprolol

• MERIT-HF: Metoprolol tartrate • Preceded by 2 previous trials in CHF (MDC, RESOLVD) • 3,991 patients, mean f/u 12months, class II-III • Mean EF 28% • Results: stopped early as total mortality + all cause hospitalization was reduced 38% to 32% (p=.00012) and total mortality reduced 10.8% to 7.2 % (p<.0001) • JAMA.2000;283:1295 Slide 55

CAPRICORN

Carvedilol in post-MI patients with Reduced EF: All-Cause Mortality 1.00

0.90

0.80

0.70

0.60

0 0 0.5

Carvedilol n=975 Placebo n=984 Risk reduction  23%

P

=.031

Mortality rates: Placebo 15%; Carvedilol 12%

1

Slide 56

1.5

2 2.5

Years

–1390.

COPERNICUS

• Carvedilol in Class III-IV Heart Failure • Inclusion: EF<25%, class III-IV,euvolemic • 2,289 patients, mean f/u 10.4 months, stopped early • Mortality 18.5% (placebo) vs. 11.4% with carvedilol 35% reduction (p<.00013) • No difference in withdrawal rates • Mortality curves diverge within 3 weeks; thus, beneficial effects are not delayed and can occur at low dose NEJM 2001; 344:1651 Slide 57

100 90 80

COPERNICUS

All-cause Mortality

Packer M et al.

N Engl J Med.

2001;344:1651 –1658.

Coreg (carvedilol) Prescribing Information. GlaxoSmithKline, Research Triangle Park, NC. Mar 2003.

Carvedilol

n=115

Risk reduction



35%

P

=.0014

Placebo

n=113

70 60

Mortality rates: Placebo 19.7%; Carvedilol 12.8%

0 0 3 6 9 12 Months 15 18

Slide 58

21

COMET

• First head-to-head mortality study comparing two beta blocking agents in CHF--carvedilol vs. short-acting metoprolol titrate • 3,029 patients, class II-III, EF<35%, 80% male, 99% Caucasian • Carvedilol compared to metoprolol reduced annual mortality from 10.0% to 8.3% and prolonged median survival by 1.4 years • Lancet 2003;362:7 Slide 59

Beta Blockers for CHF: Summary

• Ischemic or non-ischemic CMP • All symptomatic CHF patients • Class II - IV • Hemodynamically stable and euvolemic • Even in “compensated” patients as there is a high likelihood of symptoms progression in 12 months • Beneficial effects are in addition to effects of other therapies Slide 60

Angiotensin Receptor Blockers in CHF

Trial Drugs Baseline EF Mortality vs. ACE-I Notes RESOLVD 1999 candesartan vs. enalapril Avg 27% 6.1 vs 3.7 (p=NS) <40% 17.7 vs. 15.9 (p= NS) ELITE II 2000 losartan vs. captopril ValHeft 2001 CHARM 2003 valsartan candesartan <40% 19.9 vs. 19.4 (p= NS) 33% increased mortal if not on ACE-I Small decrease in mortality when added to ACE-I No increased mortality w/ beta blocker Slide 61

Angiotensin Receptor Blockers in CHF

• ARBs should be used in patients intolerant of ACE inhibitors • ARBs can be added on in patients receiving ACE inhibitors and beta blockers with a small added benefit • Increased risk of hypotension, hyperkalemia and renal insufficiency when added on to ACE-I and beta-blocker therapy Slide 62

Aldosterone Blockers in CHF

Study Drug Patients Added therapy Mortality vs. placebo Hyper kalemia RALES 1999 spironolactone Class III and IV CHF ACE-I, no beta blocker Reduced from 46.3% to 35% (p<.001) 2% EPHESUS 2003 eplerenone Post-MI w/ EF<40% or diabetes ACE-I and beta blocker Reduced from 14.6% to 8.5% (p=.008) 5.5% Slide 63

Aldosterone Blockers

• Aldosterone blockers should be used in patients with chronic heart failure with low EF (spironolactone) and in patients post-MI with heart failure with EF<40% or diabetes mellitus (eplerenone) • Contraindications: renal insufficiency (creat >2.5 mg%) or hyperkalemia (over 5.0) • Patients on aldosterone blockers must have renal function and electrolytes carefully and frequently monitored Slide 64

Digoxin and CHF: “Dig Trial”

• 1997, CHF with EF<45%, NSR, class II-III • 6,800 patients, 94% ACE-I, little beta-blocker, f/u 37 months • Total and CV mortality: No significant differences • Decreased need for hospitalization for CHF, 2% hospitalized for dig toxicity • Summary: Use digoxin for symptomatic benefit, not mortality benefit • NEJM.1997;336:525 Slide 65

Vasodilators and CHF

• V-HeFT I: 1986: preceded use of ACE-I and beta blockers for CHF • Placebo vs. prazosin vs. combined isosorbide dinitrate (avg 136 mg) with hydralazine (avg 270 mg) • 642 pts, EF<45% • All cause mortality improvement only with ISDN+Hydralazine (p=.04) • Recommend: Use for patients unable to take ACE-I or ARB • NEJM.1986;314:1547 Slide 66

Vasodilator Therapy: A-Heft

• Therapy with ISDN and hydralazine added on to standard CHF therapy.

• 1050 black patients; class III-IV heart failure, EF<45% • 76% on ACE-I/ARB, 74% on beta-blocker • Mortality reduced from 10.2% to 6.2% at 10 month follow-up (p=0.02) • NEJM 2004; 351:2049 Slide 67

NESIRITIDE (BNP)

• Inpatient intravenous infusion • Arterial and venodilator • Natriuresis and diuresis • No tolerance or proarrhythmia • Associated with hypotension • Rapid fall in PCWP • No adverse effect on mortality Slide 68

Intravenous Inotropic Agents

• • • ACC/AHA Guidelines (Circ. 2001; 104:2996.) • 1. For symptomatic systolic dysfunction (Stage C): Class III (i.e. NOT indicated): Long term intermittent use of an infusion of a positive inotropic drug (level of evidence C) • • 2. For refractory end-stage CHF (Stage D): Class IIb: Continuous intravenous infusion of a positive inotropic agent for palliation of symptoms (level of evidence C) Class III (NOT indicated): Routine intermittent infusions (level of evidence B) Slide 69

Search for Aggravating Medical Conditions

• Ischemia, arrhythmias, conduction abnormalities • Worsening valve regurgitation • Hypertension, bilateral renal artery stenosis • Anemia, thyroid disease, infection, renal failure, obstructive sleep apnea, medication noncompliance Slide 70

Patients Refractory to Pharmacologic Therapy

• Resynchronization therapy to improve heart failure (biventricular pacemaker) • Revascularization if documented ischemia • ICD implant to reduce risk of sudden arrhythmic death • Surgery: CABG, valve repair, transplant Slide 71

Case Studies

•The following are case studies that can be used for review of this presentation. Review Cases End Slide 72

Case #1

• A 49-year-old female presented to the emergency department of a community hospital with a 5-day history of chest pain. The pain was retrosternal, radiated to both arms, and was brought on by mild exertion. Chest pains increased in frequency over the 5 days.

Slide 73

Case #1

• Past medical history: No cardiovascular illness • Cardiac Risk Factors: – chronic cigarette smoker – Multiple family members with MI at age 50-60 • Physical exam: BP 120/80, HR 80 per min, Lungs clear, normal cardiac exam • ECG: normal sinus rhythm, normal • Laboratory: – total cholesterol 177mg% – triglycerides 247 mg% – HDL 27mg% – LDL 101mg% FBS 109mg% – TROPONIN=0.52 (nl< .05) Slide 74

Case #1

• Hospital course: • Patient was treated with aspirin, low molecular weight heparin (enoxaparin) and nitroglycerin topically • On day 2, patient was transferred to a tertiary hospital for cardiac catheterization • Coronary angiography showed significant single vessel coronary artery disease with a 95% stenosis of the mid-right coronary artery. There was also a 30% stenosis of the LAD and a 40% stenosis of the mid circumflex coronary artery.

• Patient underwent successful and uncomplicated stenting of the RCA.

Slide 75

Case #1

• Discharge medications: – aspirin 325 mg daily – clopidogrel 75 mg daily – atorvastatin 80 mg daily – metoprolol 50 mg bid – lisinopril 10 mg daily • Patient counseled regarding cessation of cigarette smoking Slide 76

Case #2

• A 58-year-old female presents to the emergency department with severe dyspnea, awakening her from sleep.

• HPI: two-month history of gradually worsening exertional dyspnea without chest pain • PMH: Hypertension, hyperlipidemia; non-smoker, no alcohol use • Medication on admission: amlodipine 5 mg daily Slide 77

Case #2

• Physical exam: marked respiratory distress HR 110 per min, BP 160/105, Chest: rales in all fields, Heart: regular tachycardia, S3 gallop, no murmur, Extremities: no edema • ECG: sinus tachycardia, voltage criteria for LVH, ST segment depression laterally. • CXR: cardiomegaly, pulmonary edema • Laboratory: Normal CBC. Normal electrolytes, renal function and liver enzymes Slide 78

Case #2

• Hospital course: Initially treated with intravenous furosemide and intravenous nitroglycerin with resolution of signs and symptoms of pulmonary edema and lowering of BP to 110/80 in 24 hours.

• Echocardiogram: Markedly dilated LV with severe global hypokinesis and calculated LV ejection fraction of 20%. Normal appearance of mitral and aortic valves. Mild mitral regurgitation.

• Coronary angiography: No significant coronary artery stenoses.

Slide 79

Case #2

• Diagnosis: Congestive heart failure due to idiopathic dilated cardiomyopathy in the setting of chronic hypertension.

• Patient discharged feeling well on the following medications: – lisinopril 10 mg daily – carvedilol 12.5 mg bid – spironolactone 25 mg daily – digoxin 0.125 mg daily Slide 80

Case #3

• 60-year-old male presents to the emergency room of a community hospital with a two-hour history of severe chest pain associated with severe diaphoresis, dizziness and presyncope • PMH: type 2 diabetes mellitus, no previous cardiac illness Slide 81

Case #3

• Examination: HR 80 per min BP 78/54 – Pale, diaphoretic, Lungs clear – Heart: No murmur or S3 gallop • ECG: NSR, marked ST segment elevation in leads II, III and aVF • CXR: Normal heart size, clear lung fields Slide 82

Case #3

• Course: Patient was emergently transferred to a tertiary hospital for cardiac catheterization • Hemodynamics: RA=22 mmHg PA=32/22 PCWP mean=23 mmHg • Coronary Angiography: total occlusion of proximal right coronary artery. Treated with successful and uncomplicated angioplasty and stenting. Intra-aortic balloon pump placed.

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Case #3

• Diagnosis: Acute inferior wall myocardial infarction complicated by cardiogenic shock due to right ventricular infarction • Hospital course: Patient’s BP improved to 110/78 post procedure, with resolution of chest pain. Hospital course was uncomplicated. IABP removed on day #2, patient discharged on hospital day #5.

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Selected References

• Hochman JS, Sleeper LA, Webb JG, et al. Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock.. N Eng J Med. 1999;341:625-634 • Anderson JL, Adams CD, Antman EM, Bridges CM, et al. ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/ Non-ST Elevation Myocardial Infarction-2002: Executive Summary. A Report of the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Unstable Angina/Non-ST-Elevation Myocardial Infarction). J Am Coll Cardiol 2007; 50: 652-726.

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Selected References

• Adams KF, Lindenfeld J, Arnold JMO, et al. Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guidelines. J Cardiac Failure. 2006;12:10-38.

• Packer M, Coats AJ, Fowler MB, et al, Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of Carvedilol on Survival in Severe Chronic Heart Failure. N Eng J Med. 2001;344:1651 1658.

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