1. Program Information

2. Cardiogenic Shock, Acute Coronary Syndromes and Heart Failure
Fredric Ginsberg, M.D.
Joseph Parrillo, M.D.
This presentation will review the current recommendations regarding the evaluation and treatment of 3 important and common cardiovascular illnesses: cardiogenic shock, acute coronary syndromes, and heart failure due to LV systolic dysfunction.

3. 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
Cardiogenic shock is defined as persistent hypotension and tissue hypoperfusion due to cardiac dysfunction, in the presence of adequate intravascular volume. Clinical signs of cardiogenic shock include sustained systolic BP less than 90 mm Hg, tachycardia, oliguria, cool extremities, and altered mental status. Hemodynamic findings include cardiac index less than 2.2 L/min and pulmonary artery occlusion pressure over 15 mm Hg.
Parrillo, J 3

4. 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
The most common cause of cardiogenic shock is left ventricular failure due to massive acute myocardial infarction. Mechanical complications of acute myocardial infarction that lead to cardiogenic shock include acute, severe mitral regurgitation due to papillary muscle rupture, ventricular septal rupture, and cardiac free-wall rupture. Right ventricular infarction complicating acute inferior wall infarction often leads to cardiogenic shock. Causes of cardiogenic shock other than acute myocardial infarction include end-stage cardiomyopathy, fulminant myocarditis, and transient apical ballooning syndrome, or stress cardiomyopathy. 4

5. CARDIOGENIC SHOCK Evolution of the Disease
• Frequently, shock develops after presentation for myocardial infarction.
- SHOCK Registry
• At presentation % in shock
• Within 24 hours %
(median delay = 7 hours)
- GUSTO Trial
• At presentation 11% in shock
• After admission 89%
In patients with acute myocardial infarction who develop shock, only 25% will present in shock at hospital admission. Shock often develops during the first day of hospitalization. In the SHOCK trial registry, the mean time from onset of myocardial infarction to shock was seven hours.
SHOCK Registry, Circulation 1995;91:873-81
GUSTO J Amer Coll Cardiol 1995;26:668-74 5

6. Schematic Diagram of Stunned Myocardium
Clamp
Wall motion
abnormality
Coronary occlusion
Wall motion
abnormality
during
occlusion
Coronary reperfusion
Persistent wall motion abnormality
(despite reperfusion
and viable myocytes)
The pathophysiology of cardiogenic shock due to left ventricular failure from acute myocardial infarction includes irreversible left ventricular dysfunction due to myocardial necrosis. Potentially reversible left ventricular dysfunction may also be present, due to processes termed myocardial stunning and hibernation. Stunned myocardium demonstrates persistent dysfunction after ischemia has been relieved, for example with thrombolysis or angioplasty. Function will return in hours to days.
Return of
function
Gradual return of
function (hours to days)
From Kloner, R.A., Am J Med 1986;86:14. 6

7. Atherosclerotic narrowing
Hibernating Myocardium
Wall motion abnormality
Atherosclerotic narrowing
Hibernation refers to dysfunctional myocardium due to chronic ischemia. Ventricular wall motion abnormality due to hibernation is potentially reversible with restoration of normal blood flow. Necrosis, stunning and hibernation may all be present to varying degrees in patients with cardiogenic shock.
Wall motion abnormality
due to chronic ischemia
without infarction
From Kloner, R.A., Am J Med 1986;86:14. 7

8. Ischemic Myocardium Cell death Reperfusion
Significant residual stenosis
Segments with myocardial stunning
Segments with both stunning and hibernation
Segments with hibernating myocardium
Inotropic support
This schematic summarizes the pathophysiology of left ventricular dysfunction seen in cardiogenic shock due to acute myocardial infarction. No return of function is anticipated in areas of myocardium which become necrotic. Reperfusion therapy in acute myocardial infarction may result in stunned myocardium, and function of these areas will return after a period of supportive therapy. Areas of myocardium supplied by stenotic coronary arteries may be dysfunctional as a result of chronic ischemia, and function can recover with revascularization.
Relief of ischemia
No return of function
Return of myocardial function 8

9. 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
Recognizing the presence of cardiogenic shock early in its course is of paramount importance. Patients should be assessed rapidly to diagnose the cause of cardiogenic shock, including evaluation of the ECG and echocardiography. Patients are evaluated regarding the need for sedation, supplemental oxygen, intubation and mechanical ventilation. Initial medical therapy includes fluid challenge for significant hypotension, if there is no evidence of pulmonary edema. Dopamine or norepinephrine are used to maintain arterial pressure adequate for tissue perfusion. 9

10. 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
Intra-aortic balloon counterpulsation is very useful to support patients with cardiogenic shock. Beneficial hemodynamic effects include improving cardiac output by decreasing after-load and improving coronary blood flow, without increasing myocardial oxygen demand. Current ACC/AHA guidelines list balloon counterpulsation as a class I recommendation for patients with cardiogenic shock not responding quickly to other measures. It may result in short term functional improvement of ischemic myocardium. It likely does not improve outcomes unless its use is combined with coronary revascularization. 10

11. Revascularization in Acute Myocardial Infarction
Early revacularization in Acute Myocardial Infarction complicated by cardiogenic shock
Overall 30-Day Survival in the Study
Hochman, J.S., et al, N Engl J Med 1999;341:
Proportion Alive
Days after Randomization
0.6
0.2
0.0
0.8
Revascularization (n=152)
Medical therapy (n=150)
1.0
0.4 5 10 15 20 25 30
Survival = 53%
Survival = 44%
p =0.11
The landmark SHOCK trial prospectively randomized 302 patients with cardiogenic shock due to acute myocardial infarction and left ventricular failure to either emergency early revascularization with PCI or bypass surgery versus initial medical stabilization with drug therapy and balloon counterpulsation. Thirty day survival was higher in the revascularization group, although this improvement did not reach statistical significance. 11

12. SHOCK Trial Mortality Revasc Med Rx % 100 P = 0.11 P = 0.02780
66.4
63.1 % 56 60
54.3
50.3
46.7 40
Revasc
Med Rx 20
30 days
6 months
1 year 12

13. 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)
Therefore, emergency revascularization with either coronary angioplasty or coronary bypass surgery is a class I indication in current AHA/ACC guidelines for the treatment of cardiogenic shock due to acute myocardial infarction in patients younger than age 75, if it can be performed within 36-hours of the onset of shock. Patients older than age 75 had worse outcomes with emergency revascularization in the SHOCK trial, but the number of patients in this age group was small. Careful patient selection for urgent revascularization is important in those older than 75 years. Rapid transfer of patients with cardiogenic shock from hospitals without revascularization capability to those with revascularization facilities should occur early in the course of the illness. 13

14. 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.
Unfortunately, invasive procedures are under-used in patients with cardiogenic shock. Registry data indicate that in 2001, only 44% of patients with cardiogenic shock underwent emergency revascularization. Another database reported in 2004 that only 54.4% of patients with cardiogenic shock underwent emergency angioplasty. It is necessary to improve systems of care for myocardial infarction patients in order to translate the benefits of early revascularization to wider implementation.
Babaev A et al Circ (19):1811 (abstract) 14

15. 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.
The first bullet: awkward language to juxtapose the words “moderate” and “severe”. Can we just say “moderately depressed”
Hochman JS. Circ .2003;107: 15

16. 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.
Nitric oxide synthase inhibition can raise blood pressure in patients with persistent cardiogenic shock after percutaneous intervention.
The mechanism of this effect is unknown, but may involve both an effect on coronary and other organ perfusion pressure, and potentially an improvement in cardiac function.
Cotter, Eur Heart J. 2003:24: 16

17. Acute Coronary Syndromes: Definitions
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
Unstable angina:
angina at rest (usually >20 minutes)
new-onset of class III or IV angina
increasing angina (from class I or II to III or IV)
Braunwald. Circulation 2002; 106:
Acute myocardial ischemia causes symptoms and signs referred to as acute coronary syndromes (or ACS). ACS can be due to myocardial infarction, with or without ST segment elevation on ECG, or unstable angina, which is defined as prolonged angina at rest, new onset of angina with minimal provocation, or worsening of stable angina. ACS is responsible for 1.6 million hospitalizations annually in the United States, with 1.3 million admissions due to non-ST elevation myocardial infarction or unstable angina. This presentation will discuss ACS due to non-ST elevation myocardial infarction and unstable angina. 17

18. Hospitalizations in the US Due to Acute Coronary Syndromes
~1.8 Million Hospital Admissions
UA/NSTEMI
1.42 Million
Admissions
Per Year
STEMI
0.41 Million
Admissions
Per Year
National Hospital discharge survey National Center for health Statistics/Centers for Disease Control and Prevention. Series 13, No. 14. September 18

19. Pathogenesis of Acute Coronary Syndromes
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
White HD. Am J Cardiol 1997;80 (4A):2B-10B.
The pathogenesis of ACS most often involves fissuring and disruption of an atherosclerotic plaque in a coronary artery. This leads to platelet adhesion and activation, stimulating formation of an occluding thrombosis. If the coronary is totally occluded, ST elevation infarction often occurs. Non-ST elevation myocardial infarction and unstable angina often result from a partially occlusive coronary thrombosis or distal microvascular thromboembolism from the plaque-associated thrombus. Coronary vasoconstriction or vasospasm may also play a role.
Acute coronary syndromes occur as a result of thrombus formation in response to rupture of an atherosclerotic plaque in the vessel wall. Spontaneous or intervention-induced plaque rupture promotes adhesion of platelets from the circulation, followed by platelet activation and platelet aggregation. Platelet aggregation leads to the formation of partially occlusive coronary thrombi, which clinically manifest as unstable angina (with occlusions > 70%), or, if prolonged occlusion results in myocardial damage, as NSTEMI. NSTEMI is caused by dislodgement and embolization of platelet-rich microthrombi into the coronary microvasculature, blocking blood flow, and causing heart muscle death. Complete occlusion of coronary arteries (>90%) manifests clinically as STEMI. 19

20. Structure of Thrombus Following Plaque Disruption
UA/NSTEMI: Partially-occlusive thrombus (primarily platelets)
Intra-plaque thrombus (platelet-dominated)
Plaque core
STEMI: Occlusive thrombus (platelets, red blood cells, and fibrin)
Intra-plaque thrombus (platelet-dominated)
SUDDEN DEATH
This graphic depicts how plaque rupture and partially occlusive or totally occlusive thrombus leads to myocardial ischemia and infarction.
The clinical manifestation of coronary thrombosis depends on the extent and duration of thrombotic occlusion. Unstable angina and non-ST-segment elevation MI are characterized by mural, platelet-rich thrombi, which do not completely block coronary blood flow and therefore cause ischemia of relatively short duration.
The aggregated platelets can serve as a substrate for further thrombus propagation, leading to formation of an occlusive red thrombus formed by entrapment of red blood cells within the fibrin mesh. This complete occlusion results in abrupt and persistent ischemia that clinically manifests as ST-segment elevation MI. Left untreated, occlusion of the coronary arteries can lead to sudden cardiac death.
UA = Unstable Angina
NSTEMI = Non-ST-segment Elevation Myocardial Infarction
STEMI = ST-segment Elevation Myocardial Infarction
White HD. Am J Cardiol 1997;80 (4A):2B-10B. 20

21. Diagnostic Algorithm + Troponin or + CK-MB &/or
Therapeutic goal: rapidly break apart fibrin mesh to quickly restore blood flow
ST-segment elevation MI
Non-ST Elevation ACS*
Non-ST Elevation MI
+ Troponin or + CK-MB
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
&/or
The therapeutic goal in ST elevation myocardial infarction is to rapidly restore blood flow through the occluded coronary artery. This can be done with emergency coronary interventions such as angioplasty and stenting, or with fibrinolytic drugs. In non-ST elevation myocardial infarction, the diagnosis is supported by the presence of acute ST segment depression on ECG and/or elevation of serum cardiac biomarkers. The goal in non-ST elevation myocardial infarction is to prevent progression to complete coronary artery occlusion and to restore adequate blood flow to ischemic myocardium.
During the past 20 years, management of acute coronary syndromes (ACS) has focused on rapid identification and treatment of patients with STEMI. However, it is now recognized that the same urgency should also be used for management of patients with NSTEMI or unstable angina, because their morbidity and mortality rates are similar to those of patients with STEMI. Thus, in modern practice, the goal is to rapidly identify and appropriately treat not only patients with STEMI (who benefit from fibrinolytic therapy), but also high-risk NSTE ACS patients who may benefit from ACC/AHA Guidelines-recommended management, including early GP IIb-IIIa inhibitor therapy and early diagnostic catheterization.
Braunwald E, et al 21

22. 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:
0.00
0.05
0.10
0.15
0.20
0.25 3 6 9 12
Probability of Death or MI
Placebo
Aspirin 75 mg
Risk ratio % CL
Months 22

23. 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:
Trial:
FRIC
(Dalteparin; n = 1,482)
FRAXIS
(nadroparin; n = 2,357)
ESSENCE
(enoxaparin; n = 3,171)
TIMI 11B
(enoxaparin; n = 3,910) 
(p= 0.032)
(p= 0.029)
LMWH
Better
UFH 6 14
Day: 23

24. Effects of Clopidogrel
This graph demonstrates the effects of Clopidogrel in addition to Aspirin in patients with ACS without ST-Segment Elevation 2 4 6 8 10 12 14
Death, MI, or Stroke
Clopidogrel + ASA 3 9
Placebo + ASA
Months of Follow-Up
11.4%
9.3%
20% RRR
P < 0.001
N = 12,562 %
N Engl J Med. 2001;345:
Clopidogrel provided a 20% relative risk reduction in the composite outcome of MI, stroke or CV death (95% CI , P < 0.001). Overall there were 719 (11.4%) first events in the placebo group and 582 (9.3%) in the clopidogrel group. The hazard rate curves began to separate within the first few hours after therapy initiation and continued to diverge over the remainder of the trial. 24

25. Hospital Care Anti-Thrombotic Therapy
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
None
Enoxaparin preferred over UFH unless CABG is planned within 24 hours
Braunwald. Circulation 2002;106: 25

26. Hospital Care Platelet GP IIb/IIIa Inhibitors (1)
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
None
Braunwald. Circulation 2002;106: 26

27. Hospital Care Platelet GP IIb/IIIa Inhibitors (2)
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.
None
Braunwald. Circulation 2002;106: 27

28. Hospital Care Anti-ischemic Therapy (1)
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.
None
Braunwald. Circulation 2002;106: 28

29. Hospital Care Anti-Ischemic Therapy (2)
IIa
IIb
III
ACE inhibitor for all ACS pts
Extended-release CA2+ blocker instead of β-blocker
Immediate-release Ca2+ blocker with β-blocker
None
Long-acting Ca2+ blocker for recurrent ischemia, if no contraindications and NTG + β-blocker used fully C
Braunwald. Circulation 2002;106: 29

30. ST-segment Depression Predicts Higher Risk of Mortality in ACS
% Cumulative Mortality at 6 Months
10% 8% 6% 4% 2%
ST-segment depression 8.9%
ST-segment elevation 6.8%
T-wave inversion 3.4%
ST segment depression during chest pain has been shown to have a significant predictive value for increased mortality.
The findings of the long-term mortality analysis from Dr. Savonitto of the GUSTO IIb trial revealed that patients who presented initially with ST-segment depression and who were managed with aspirin plus a thrombin inhibitor (UFH) during initial hospitalization experienced higher mortality at 6 months than patients who presented with ST-segment elevation MI and were treated with fibrinolytics. This indicates the need for more aggressive treatment for NSTE ACS to prevent early MI and resultant long-term mortality.
Savonitto S. J Am Med Assoc 1999; 281:
Days from randomization 30

31. Mortality Rates According to Level of Cardiac Troponin
Similarly, the degree of elevation of cardiac troponin also is correlated with worse survival. Higher peak troponin levels predict more adverse events.
Mortality Rates According to Level of Cardiac Troponin
The prognostic value of baseline cardiac troponin values was assessed in 1404 patients with UA or NSTEMI enrolled in the prospective, randomized Thrombolysis in Myocardial Ischemia Phase IIIB trial (TIMI-IIIB).
Mortality at 6 weeks was significantly higher in 573 patients with troponin I levels ≥ 0.4 ng/mL than in 831 patients with levels < 0.4 ng/mL. Each 1 ng/mL increment was associated with a significant (P = 0.03) increase in the risk of death after adjustment for baseline variables that were independently predictive of death.
Cardiac troponin T levels are interchangeable with troponin I levels.
Thus, measurement of cardiac troponin levels permits the early identification of patients with ACS at increased risk of death. However, troponin levels may not be detectable up to 6 hours after an event.
Antman EM, Tanasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335: 31

32. 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
Patients who present with ACS may stabilize and have a relatively good prognosis, or they may develop complications including transmural infarction, heart failure, arrhythmias and death. Tools such as the TIMI risk score have been developed to aid in the risk-stratification of patients who present with ACS. This table lists the 7 factors which have been shown to be associated with an increase the risk of serious complications. 32

33. Number of TIMI Risk Factors Predicts Short-Term Recurrent Events
The presence of the characteristics listed in the TIMI risk score can be used to estimate prognosis. The higher the number of risk factors, the worse the prognosis. If 5, 6 or 7 risk factors are present, there is a 26-41% risk of severe adverse event occurring within two weeks. 33

34. TIMI UA Risk Score: Primary Endpoint at 6 mos Death/MI/ACS Rehosp (%)
CI (0.33, 0.91)
CONS
INV
11.8
20.3
12.8
16.1
19.5
30.6 5 10 15 20 25 30 35
Low
Intermed. 3-4
High
OR=0.75
CI (0.57, 1.00)
Death/MI/ACS Rehosp (%)
The TIMI risk score has also been evaluated as a predictor of outcomes after therapeutic interventions. If patients have a low score, under 2, outcomes with medical or conservative management are equivalent to results with an invasive approach. However, in patients with intermediate or high risk scores, a strategy utilizing early cardiac catheterization results in improved outcomes.
% of Pts: % % % 34

35. Troponin and ST-Segment Shift Predict Benefit of Invasive Treatment Strategy
The presence or absence of troponin elevation and ST segment changes on ECG during symptoms can be used to guide management. Invasive strategies utilizing routine early cardiac catheterization does not seem to improve outcomes in patients who do not have these findings. However, ST changes or troponin elevation should lead to strong consideration of early coronary revascularization.
Cannon. J Invas Cardiol 2003; 15:22B 35

36. 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
Either early invasive or early conservative strategy if not high risk
Braunwald, Circulation. 2002:106: 36

37. 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
The revised ACC/AHA NSTE ACS Guidelines recommend that all high-risk NSTE ACS patients be treated with an early invasive management strategy. This entails administration of the following acute therapies for high-risk NSTE ACS patients: aspirin (clopidogrel, if aspirin cannot be given), beta blockers, enoxaparin (preferred) or unfractionated heparin, and a GP IIb-IIIa inhibitor (eptifibatide or tirofiban), followed by diagnostic catheterization within hours to determine the definitive management procedure (PCI, CABG surgery, or medical management) required.
Send for catheterization & revascularization within 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 37

38. Ongoing Evaluation in an Early Conservative Strategy
Recurrent
Symptoms/ischemia
Heart failure
Serious arrhythmia
Patient stabilizes
EF .40
Stress Test
Not low risk
Follow on Medical Rx
Evaluate LV function
EF < .40
Low risk
Immediate angiography
Early medical management
Braunwald E, et al
This algorithm demonstrates decision making steps if an early conservative strategy is chosen. Coronary angiography should be strongly considered if patients do not stabilize and show signs of recurrent ischemia, heart failure or serious arrhythmias. Abnormal left ventricular systolic function or significant ischemia on stress testing should also lead to consideration of coronary angiography.
Patients managed with an early conservative strategy should be continuously monitored to detect signs and symptoms of continuing/recurrent ischemia. Patients with these features, as well as those who develop heart failure or serious arrhythmia, should immediately undergo diagnostic angiography.
Patients whose condition stabilizes should be evaluated by stress testing and for left ventricular function in order to identify additional patients who would benefit from immediate angiography (i.e., those with intermediate-to high-risk features on stress testing and those with left ventricular ejection fraction < 40%).
In patients with a low-risk profile on stress testing, medical therapy should be continued. 38

39. 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: 39

40. 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: 40

41. Recommendations for Revascularization
Braunwald, Circulation. 2002:106: 41

42. ACC/AHA REVISED GUIDELINES
UA/NSTEMI
High Risk *
ASA, Heparin/Enox., 
 block., Nitrates, Clopidogrel 
RISK STRATIFY
Low Risk
Braunwald E, et al. Circ. 2002;106:1893.
* Recurrent ischemia; Trop; ST; LV failure/dysf.;
hemodynamic instability; VT; prior CABG
 Enoxeparin. Preferred to UFH (IIa)
 If coronary arteriography >24 hours 42

43. ACC/AHA REVISED GUIDELINES
LMCD, 3VD+LV Dys.,
or Diab. Mell.
CABG
High Risk
Cor. Arteriography
1 or 2VD, Suitable
for PCI
Normal
Clopidogrel,
IIb/IIIa inhib.
Consider Alternative
Diagnosis
Discharge on ASA, Clopidogrel, Statin, ACEI
PCI
Braunwald E, et al. Circ. 2002;106:1893.
Braunwald E, et al.
Circ. 2002;106:1893. 43

44. Discharge Medications
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
None
ACE Inhibitor: CHF, EF < 40%, DM, or HTN
Braunwald, Circulation. 2002:106:
Braunwald. Circulation 2002;106: 44

45. Death or Major Cardiovascular Events
This graph displays the all-cause death or major cardiovascular events in all randomized subjects
Cannon CP, et al. N Engl J Med. 2004:350: 45

46. Reductions in Major Cardiac End Points
Cannon CP, et al N Engl J Med. 2004:350: 46

47. Risk Factor Modification
Braunwald, Circulation. 2002:106: 47

48. 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
Heart failure is a very common health problem. Approximately 5 million Americans suffer with heart failure, and more than 550,000 new cases are reported annually. Over 1 million hospital discharges in the United States list heart failure as the primary diagnosis each year. The high prevalence of heart failure places a large economic burden on the health care system.
Despite many advances in therapy, the prognosis for patients with heart failure remains poor. Mortality rates are high, and patients discharged from the hospital with heart failure have high rates of readmission.
SCOPE OF THE PROBLEM: #OF PTS, HEALTHCARE $$, POOR PROGNOSIS
Congestive heart failure (CHF) afflicts approximately 5 million people in the United States. It is estimated that there are 550,000 new cases of heart failure annually. Roughly equal numbers of men and women have CHF. Almost all CHF patients will have at least one acute episode with symptoms requiring hospitalization and treatment with intravenous medications to stabilize their condition. The incidence of heart failure is 10 per 1000 for individuals that are over 65 years of age. There is a tremendous economic burden due to heart failure. CHF now represents the most common cause of hospitalization in patients over 65 years of age. The prognosis of this condition in the absence of optimal treatment remains poor. Only 50% of CHF patients survive for 5 years or more.
Numbers based on 2000 data.
American Heart Association Heart and Stroke Statistical Update. Dallas, Tex: AHA; 2002. 48

49. 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
Fibrosis, apoptosis, hypertrophy, cellular/ molecular alterations, myotoxicity
Remodeling and progressive
worsening of LV function
BEGINS WITH ANY INJURY/STRESS
MALADAPTIVE NeuroHORMONAL ACTIVATION
The pathophysiology of systolic heart failure involves a process termed ventricular remodeling. This process is initiated by injury to heart muscle from illnesses such as hypertension, myocardial infarction or valvular disease. The response to myocardial injury, increased wall tension and a fall in left ventricular performance includes activation of neurohormonal systems, including the renin-angiotensin-aldosterone system and the sympathetic nervous system. This neurohormonal activation leads to myocardial fibrosis, myocyte necrosis and progressive left ventricular dilatation and worsening systolic function. Systemic vasoconstriction and tachycardia lead to further deterioration in left ventricular function. Worsening left ventricular function leads to the typical heart failure symptoms of fatigue due to reduced cardiac output, and dyspnea and edema due to pulmonary and peripheral venous congestion.
Peripheral vasoconstriction
Hemodynamic alterations
Heart failure symptoms
Morbidity and mortality
Arrhythmias
Pump failure
Fatigue Activity altered Chest congestion Edema Shortness of breath
RAS, renin-angiotensin system; SNS, sympathetic nervous system. 49

50. LV Remodeling After Anteroseptal MI
1 week
3 months
DILATATION, CHANGE IN GEOMETRY
These echocardiographic images demonstrate left ventricular remodeling. One week after an acute anteroseptal myocardial infarction, left ventricular volume is increased and ejection fraction is reduced, seen in the image on the left. Three months later, without additional acute infarction, left ventricular remodeling has resulted in further dilation of left ventricle and further reduction in ejection fraction, seen in the image on the right.
EDV 137 mL ESV 80 mL
EF 41%
EDV 189 mL ESV 146 mL
EF 23%
Apical 4 Chamber View 50

51. Drugs for Heart Failure
ACE-inhibitors
Beta-blockers
Angiotensin receptor blockers
Aldosterone antagonists
Loop diuretics
Nitrates with hydralazine
Digoxin
Nesiritide, inotropic agents 51

52. ACE-Inhibition and CHF Trials
SAVE--captopril, 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, CHF pts, class II-III, EF<35%, f/u 41 mos, 2569pts. Mortality reduced from 39% to 35% NEJM 1991;325:293
SOLVD--enalapril, Asymptomatic LV dysfunction, EF<35%, f/u 37 mos, pts Non-significant reduction in mortality, significant reduction in CHF and hospitalization NEJM 1992;327:685
Studies using ACE-inhibitors as treatment for systolic heart failure were reported in the early 1990’s. These studies showed consistent reduction in mortality in patients with New York Heart Association classes 2 and 3 heart failure. When patients with asymptomatic left ventricular dysfunction were treated with ACE-inhibitors, significant reduction in the development of heart failure symptoms and in hospitalization for heart failure was seen. 52

53. 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 :1450
A meta-analysis of 32 ACE-inhibitor trials which enrolled over 7,000 patients revealed an absolute mortality reduction of 6% with significant improvement in symptoms and functional
class. All ACE –inhibitor drugs are felt to be beneficial in systolic heart failure.
28% mortality reduction 53

54. 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
Adaptive compensatory mechs vs maladaptive
Beta-blocker therapy was then studied. The rationale for this approach was based on the observations that catecholamine levels are high in patients with heart failure, and the higher the levels then the more severe the condition. It is known that excessive catecholamines have deleterious effects on myocytes including inducing hypertrophy and apoptosis. Catecholamines also worsen ischemia and are arrhythmogenic. 54

55. 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
The MERIT-HF trial reported the experience using the cardioselective, long-acting formulation of metoprolol. In these patients with systolic heart failure, significant reductions in mortality and hospitalizations was seen with metoprolol when added to ACE-inhibitor therapy.
35% mortality reduction (again) 55

56. Proportion Event-free
CAPRICORN
Carvedilol in post-MI patients with Reduced EF: All-Cause Mortality
0.5 1
1.5 2
2.5
Carvedilol n=975
Placebo n=984
Proportion Event-free
23%
P=.031
Risk reduction
Mortality rates: Placebo 15%; Carvedilol 12%
1.00
0.90
0.70
0.60
0.80
The CAPRICORN Study used the beta and alpha-blocker carvedilol in post-myocardial infarction patients with reduced ejection fraction. Survival was improved with the use of this medication.
All death 15%vs 12% All death or CV admit 37%vs. 35% (p=.2)
The CAPRICORN Investigators. Lancet. 2001;357:1385–1390.
Years 56

57. Carvedilol in Class III-IV Heart Failure
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
Carvedilol was also studied in the most severe heart failure patients whose left ventricular ejection fractions were below 25% and who were in New York Heart Association Class 3 or 4. In this study, called COPERNICUS, a very significant mortality benefit was seen with this drug.
NEJM 2001; 344:1651 57

58. COPERNICUS All-cause Mortality
% Survival
Carvedilol
Placebo 3 6 9 12 15 18 21
Months
100 90 80 60 70
Risk reduction
 35%
n=115
n=113
Packer M et al. N Engl J Med. 2001;344:1651–1658.
Coreg (carvedilol) Prescribing Information. GlaxoSmithKline, Research Triangle Park, NC. Mar 2003.
Mortality curves for carvedilol and placebo began to diverge as early as three weeks after initiation of therapy in this study.
Mortality rates: Placebo 19.7%; Carvedilol 12.8% 58

59. 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
A study called the COMET trial compared therapy with carvedilol to treatment with short-acting metoprolol. It showed better survival with carvedilol. 59

60. 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
In summary, multiple trials have demonstrated improved outcomes with the use of beta-blockers in patients with ischemic and nonischemic cardiomyopathy, LV dysfunction and heart failure. Mortality benefits are in addition to benefits seen with ACE-inhibitors. Beta-blockers approved for use in heart failure are carvedilol, bisoprolol, and sustained-release metoprolol. 60

61. 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)
ELITE II 2000
losartan vs. captopril
<40%
17.7 vs (p= NS)
ValHeft 2001
valsartan
19.9 vs (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/ beta-blocker
Angiotensin receptor blockers have been examined in several studies in patients with heart failure. Valsartan and candesartan have been found to improve symptoms and life expectancy in patients intolerant to ACE-inhibitors. 61

62. 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
When angiotensin receptor blockers were added to ACE-inhibitor therapy in the CHARM study, a small improvement in mortality was seen, although the incidence of hyperkalemia, hypotension and renal insufficiency was greater. 62

63. 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%
Aldosterone blockers are an important part of medical therapy for severe heart failure. The RALES trial showed significant mortality benefit in functional class 3 and 4 patients when spironolactone was added to ACE-inhibitor therapy. In another trial, eplerenone, when added to ACE-inhibitor and beta-blocker therapy, was shown to improve survival in patients after myocardial infarction who were diabetic or who had heart failure. 63

64. 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
Careful monitoring of renal function and serum potassium levels is essential when aldosterone blockers are used. These drugs are indicated in patients with severe systolic heart failure. Contra-indications include renal insufficiency and baseline hyperkalemia. 64

65. 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
Digoxin has a long history of use in patients with heart failure. However, the large “dig trial” did not show a mortality benefit with digoxin therapy, although hospitalizations for heart failure were reduced. Digoxin can be used in patients with persistent symptoms who are already taking ACE-inhibitors or angiotensin receptor blockers, beta-blockers, and aldosterone blockers. Renal insufficiency is a relative contra-indication. 65

66. 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
An early study called VAL-Heft showed improved mortality in heart failure patients with the use of the combination isosorbide dinitrate with hydralazine. 66

67. 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
This drug combination is indicated for African-American patients with heart failure and should be considered for other patients who are intolerant to ACE-inhibitors and angiotensin receptor blockers. 67

68. 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
Several parenteral medications are available for use in patients hospitalized with heart failure. Nesiritide is a recombinant form of BNP which has arterial and venous dilating properties. It can promote a modest diuresis and may result in a significant, rapid fall in pulmonary capillary occlusion pressure. It can aggravate systemic hypotension. Preliminary studies have shown no adverse effect on mortality. Further studies to assess the short and long-term benefits of nesiritide are ongoing. 68

69. 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)
Intravenous inotropic drugs have fallen out of favor, as their use is associated with an increase in mortality in heart failure patients. Long-term continuous or intermittent inotrope infusions are not used. Inotropes should only be used to improve end-organ perfusion in patients in shock, or for palliation of symptoms in end-stage disease. 69

70. 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
When patients are admitted to hospital with decompensated chronic heart failure, there should be a careful search for aggravating co-morbidities. Often, non-adherence with medications or with salt and fluid restrictions is identified. Aggravating cardiac conditions include myocardial ischemia, arrhythmias such as atrial fibrillation, or worsening valve regurgitation. Extra-cardiac conditions such as anemia, thyroid disease, worsening renal function and infection are often present. 70

71. 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
When patients continue to have severe heart failure symptoms despite appropriate medical therapy, other options are available. If ECG shows QRS duration greater than 120 msec and left ventricular ejection fraction is below 35%, then resynchronization therapy with a biventricular pacemaker is indicated. Revascularization should be considered when significant ischemia is demonstrated. Cardiac surgery options include coronary bypass and valve repair or replacement in appropriate patients. Lastly, therapy with an implantable defibrillator, while not a treatment for heart failure symptoms, can extend life by preventing sudden death caused by ventricular arrhythmias. 71

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

73. 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. 73

74. 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) 74

75. 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. 75

76. 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 76

77. 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 77

78. 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 78

79. 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. 79

80. 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 mg daily 80

81. 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 81

82. 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 82

83. 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. 83

84. 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. 84

85. 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:
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: 85

86. Selected References
Adams KF, Lindenfeld J, Arnold JMO, et al. Executive Summary: HFSA 2006 Comprehensive Heart Failure Practice Guidelines. J Cardiac Failure ;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 ;344: 86