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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%
SHOCK Registry, Circulation 1995;91:873-81
GUSTO J Amer Coll Cardiol 1995;26:668-74
Slide 5
Schematic Diagram of Stunned
Myocardium
Clamp
Wall motion
abnormality
Wall motion
abnormality
during
occlusion
Coronary occlusion
Coronary reperfusion
Persistent wall motion
abnormality
(despite reperfusion
and viable myocytes)
Return of
function
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
Ischemic Myocardium
Cell death
Significant
residual
stenosis
Reperfusion
Segments with Segments with
myocardial
both stunning
stunning
and hibernation
Inotropic
support
No return
of function
Return of
myocardial function
Slide 8
Segments with
hibernating
myocardium
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
Proportion Alive
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
Hochman, J.S., et al, N Engl J Med
1999;341:625-34.
0
5
p =0.11
10
15
20
Days after Randomization
Slide 11
25
30
100
80
SHOCK Trial Mortality
P = 0.11
P = 0.027
P < 0.03
66.4
63.1
%
56
60
46.7
54.3
50.3
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.
Cotter, Eur Heart J. 2003:24:1287-1295
Slide 16
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
STEMI
1.42 Million
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
Plaque rupture
White HD. Am J Cardiol 1997;80 (4A):2B-10B.
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
STEMI:
Occlusive thrombus (platelets,
red blood cells, and fibrin)
UA/NSTEMI:
Partially-occlusive thrombus
(primarily platelets)
Intra-plaque
thrombus
(platelet-dominated)
Plaque core
UA = Unstable Angina
NSTEMI = Non-ST-segment Elevation Myocardial
Infarction
STEMI = ST-segment Elevation Myocardial
Infarction
Intra-plaque
thrombus
(platelet-dominated)
SUDDEN
DEATH
Slide 20
Plaque core
White HD. Am J Cardiol 1997;80
(4A):2B-10B.
Diagnostic Algorithm
&/or
ST-segment 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)
Non-ST Elevation ACS*
+ Troponin
or + CK-MB
Non-ST Elevation MI
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
Probability
of Death or MI
Placebo
0.20
0.15
0.10
Aspirin 75 mg
0.05
Risk ratio 0.52
95% CL 0.37 - 0.72
0.00
0
3
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.
Braunwald. Circulation. 2002;106:1893-2000.
www.acc.org/clinical/guidelines/unstable/unstable.pdf
Trial:
Day:

6
FRIC
(Dalteparin; n = 1,482)

14
FRAXIS
(nadroparin; n = 2,357)

(p= 0.032) 14

(p= 0.029) 14
ESSENCE
(enoxaparin; n = 3,171)
TIMI 11B
(enoxaparin; n = 3,910)
.75
LMWH
Better
Slide 23
1.0
UFH
Better
1.5
Effects of Clopidogrel
This graph demonstrates the effects of Clopidogrel in addition to Aspirin in
patients with ACS without ST-Segment Elevation
%
Death, MI, or Stroke
14
11.4
%
9.3%
Placebo
+ ASA
12
10
8
Clopidogre
l
+ ASA
6
4
N Engl J Med. 2001;345:494502.
2
0
0
3
6
9
Months of Follow-Up
Slide 24
20% RRR
P < 0.001
N=
12,562
12
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 ↑ BP persists with NTG+ β –
blocker, 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 βblocker
Immediate-release Ca2+ blocker with βblocker
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
ST-segment Depression Predicts
Higher Risk of Mortality in ACS
% Cumulative Mortality at 6 Months
10%
ST-segment depression
8.9%
8%
ST-segment elevation
6.8%
6%
4%
T-wave inversion
3.4%
2%
Savonitto S. J Am Med Assoc 1999; 281: 707-711.
30
60
90
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
Death/MI/ACS Rehosp (%)
TIMI UA Risk Score: Primary
Endpoint at 6 mos
CONS
35
30
25
20
15
10
5
0
% of Pts:
OR=0.55
CI (0.33, 0.91)
INV
OR=0.75
CI (0.57, 1.00)
30.6
20.3
19.5
16.1
11.8
12.8
Low
0-2
25%
Intermed. 3-4
60%
Slide 34
High
5-7
15%
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
Start immediate
 Aspirin
 Heparin or low-molecular-weight heparin
 GP IIb-IIIa inhibitor
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
Evaluate LV function
Symptoms/ischemia
Heart failure
Serious arrhythmia EF < .40 EF .40
Patient
stabilizes
Stress Test
Braunwald E, et al. 2002.
http://www.acc.org/clinical/guidelines/unstable/unstable.pdf.
Not low risk
Immediate angiography
Slide 38
Low risk
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
Braunwald, Circulation. 2002:106:1893-2000.
CAD and diabetes
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.
CABG
1 or 2VD, Suitable
for PCI
Clopidogrel,
IIb/IIIa inhib.
PCI
Discharge on ASA, Clopidogrel, Statin, ACEI
Braunwald E, et al.
Circ. 2002;106:1893.
Slide 43
Normal
Consider Alternative
Diagnosis
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.
www.acc.org/clinical/guidelines/unstable/unstable.pdf
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
Activation of RAS and SNS
Remodeling and progressive
worsening of LV function
Fibrosis, apoptosis,
hypertrophy, cellular/
molecular alterations,
myotoxicity
Morbidity and mortality
Arrhythmias
Pump failure
Slide 49
RAS, renin-angiotensin system; SNS, sympathetic nervous system.
Peripheral vasoconstriction
Hemodynamic alterations
Heart failure symptoms
Fatigue
Activity altered
Chest congestion
Edema
Shortness of breath
LV Remodeling After
Anteroseptal MI
1 week
3 months
EDV 189 mL ESV 146 mL
EDV 137 mL ESV 80 mL
EF 23%
EF 41%
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
•
Slide 53
JAMA. 1995. 273:1450
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)
•
Slide 55
JAMA.2000;283:1295
CAPRICORN
Carvedilol in post-MI patients with Reduced EF: All-Cause Mortality
Proportion Event-free
1.00
Carvedilol
0.90
n=975
Risk reduction
23%
0.80
Placebo
P=.031
n=984
0.70
Mortality rates: Placebo 15%; Carvedilol 12%
0.60
0
0
0.5
1
1.5
2
2.5
The CAPRICORN
Years Investigators. Lancet. 2001;357:1385–1390.
Slide 56
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
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.
100
90
Carvedilol n=115
% Survival
Risk reduction
 35%
80
P=.0014
Placebo n=113
70
60
Mortality rates: Placebo 19.7%; Carvedilol 12.8%
0
0
3
6
9
12
15
18
Months
Slide 58
21
COMET
• First head-to-head mortality study comparing two betablocking 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
•
Slide 59
Lancet 2003;362:7
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
RESOLVD 1999
candesartan vs.
enalapril
Avg 27%
6.1 vs 3.7 (p=NS)
ELITE II 2000
losartan vs. captopril
<40%
17.7 vs. 15.9 (p= NS)
ValHeft 2001
valsartan
<40%
19.9 vs. 19.4 (p= NS)
33% increased
mortal if not on ACE-I
CHARM 2003
candesartan
Small decrease in
mortality when added
to ACE-I
No increased
mortality w/ betablocker
Slide 61
Notes
Angiotensin Receptor Blockers
in CHF
• ARBs should be used in patients intolerant of ACE
inhibitors
• ARBs can be added on in patients receiving ACEinhibitors 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
Hyper-
Study
Drug
Patients
Added therapy
Mortality vs. placebo
RALES 1999
spironolactone
Class III and IV
CHF
ACE-I, no betablocker
Reduced from 46.3% to
35% (p<.001)
2%
EPHESUS 2003
eplerenone
Post-MI w/
EF<40% or
diabetes
ACE-I and betablocker
Reduced from 14.6% to
8.5% (p=.008)
5.5%
Slide 63
kalemia
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
•
Slide 65
NEJM.1997;336:525
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
•
Slide 66
NEJM.1986;314:1547
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)
•
Slide 67
NEJM 2004; 351:2049
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.
Slide 83
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 postprocedure, with resolution of chest pain. Hospital course
was uncomplicated. IABP removed on day #2, patient
discharged on hospital day #5.
Slide 84
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.
Slide 85
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;344:16511658.
Slide 86