Transcript ACE-inhibitor or Beta

ACUTE HEART FAILURE AFTER
MYOCARDIAL INFARCTION
Nurkić Midhat MD PhD FESC
• In most patients with heart failure due to left
ventricular systolic dysfunction, the underlying
cause is coronary heart disease
• To reduce progression to heart failure in a
patient with acute myocardial infarction, it is
important to achieve the earliest possible
reperfusion, whether by thrombolysis or primary
percutaneous coronary intervention
ACUTE HEART FAILURE
Sudden development of a large
myocardial infarction or rupture of a
cardiac valve in a patient who
previously was entirely well
LV Remodelling Post MI
Acute infarction
(hours)
Infarct expansion
(hours to days)
Global remodelling
(days to months)
• Acute heart failure (AHF) is the one of the
most common disorders encountered in
medical practice, and is associated with a
high mortality and morbidity rate despite
contemporary therapy
Heart Failure after Acute MI
Cumulative HF (%)
30
25
20
15
10
5
0
0
30
Days
1
2
3
4
5
6
Years
7
8
9
10
Time
Kannel et al, 1979
Apical 4 chamber view: End diastole
LV Remodelling Post Anteroseptal MI
1 week
EDV: 137 ml ESV: 80 ml
EF: 41%
3 months
EDV: 189 ml ESV: 146 ml
EF: 23%
Sharpe N. 2000
Heart failure
• Clinical syndrome that may result from any
structural or functional cardiac disorder that
impairs the pumping ability of the heart
• It not only reduces life expectancy but is
associated with symptoms of breathlessness,
fluid retention and fatigue that markedly impair
quality of life
Pathologic Progression of CV Disease
Sudden
Death
Coronary artery
disease
Hypertension
Diabetes
Myocardial
injury
Pathologic
remodeling
Low ejection
fraction
Death
Cardiomyopathy
Pump
failure
Valvular disease
• Neurohormonal
stimulation
• Endothelial
dysfunction
• Myocardial
toxicity
Adapted from Cohn JN. N Engl J Med. 1996;335:490–498.
Symptoms:
Dyspnea
Fatigue
Edema
Chronic
heart
failure
Explosive Increase in HF
AHA.Heart Disease and Stroke Statistics – 2005 Update
• 1979 – 2002: Hospital discharges from HF rose from
377,000 to 970,000 per year
• 1992 – 2002: Deaths increased 35.3%
• Number of patients with HF is expected to double in 30
years
Similarities Between Acute MI and Acute
Decompensated HF in the US
Incidence
Acute MI
ADHF
1 million per year
1 million per year
3–4%
3–4%
2%
10%
Clearly defined
(coronary
thrombosis)
Uncertain
Beneficial
Minimal/no benefit or
deleterious compared with
placebo
Many
Level A
None
Mortality
In-hospital
After discharge (60–90
d)
Pathophysiological
target(s)
Clinical benefits of
interventions in published
clinical trials
ACC/AHA
recommendations
(Gheorghiade M, et al. Circulation 2005;112:3958-68)
Natural History of Chronic and Acute
Heart Failure
Normal heart
Chronic heart failure
5 million in the US
10 million in Europe
Initial
myocardial
injury
Heart Viability
Death
What if fluid overload
causes progressive HF?
First ADHF episode:
Pulmonary edema
ER admission
Later ADHF episodes:
Rescue therapy
ICU admission
Initial phase
Gheorghiade M. Am J Cardiol. 2005;96(suppl 6A):1-4G.
Last year
Mechanism of Worsening HF with Renal
Dysfunction
Renal dysfunction
(Schrier RW. JACC
2006;47:1-8)
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?
♥
♥
♥
♥
♥
♥
♥
♥
♥
What do these patients look like?
How do you know how much to diurese?
Is BNP useful in judging diuresis?
How to use diuretics
What do you do when the creatinine
increases?
Is ultrafiltration useful?
ACE-inhibitors or beta-blockers first?
Should beta-blockers be started in hospital?
When should you use intravenous therapy?
Predictors
of InHospital
Mortality
Fonarow, G. C. et al. JAMA
2005;293:572-580.
Copyright restrictions may apply.
Heart Failure Risk Scoring System
Lee, D. S. et al. JAMA 2003;290:2581-2587.
Mortality Rates in Acutely Decompensated
Heart Failure by Risk Score
Lee, D. S. et al. JAMA 2003;290:2581-2587.
They’re Sicker Than We Think
Mortality risk after 1st hospitalization for ADHF:
(Age, male gender, ischemia and decreased LVEF worsen
prognosis)
•In-hospital: 3%
•30-day: 7.9%
•One year: 30%
•Five years: 60%
Baker, DW et al. Am Heart J 2003; 146(2): 258-64
Ho KK, et al. Circulation 1993; 88(1): 107-15
Jong P, et al. Arch Int Med 2002; 162(15) 1689-94
Narang R ,et al. Eur Heart J 1996; 17(9) 1390-1403
Comparative Five Year Mortality
• Adenocarcinoma of the colon (IIIB): 36%
• COPD (FEV1 30-39% predicted): 53%
• ESRD (dialysis-dependent): 60-80%
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?
♥
♥
♥
♥
♥
♥
♥
♥
♥
What do these patients look like?
How do you know how much to diurese?
Is BNP useful in judging diuresis?
How to use diuretics
What do you do when the creatinine
increases?
Is ultrafiltration useful?
ACE-inhibitors or beta-blockers first?
Should beta-blockers be started in hospital?
When should you use intravenous therapy?
Congestion in HF:
Most Admitted Patients are “Wet”
100%
Admitted Patients (%)
90%
89%
74%
80%
67%
70%
65%
60%
50%
34%
40%
30%
20%
10%
0%
Any Dyspnea
Pulmonary
Congestion
(CXR)
Rales
Peripheral
Edema
(ADHERE Registry. 3rd Qtr 2003 National Benchmark Report.)
< at Rest
Dyspnea
Time Course of Events Preceding
ADHF Hospitalization
(-89 to -1)
ePAD (19)
Thoracic
Impedance (15)
SDAAM (16)
(-25 to -5)
(-21 to ?)
Dyspnea (8-9)
Edema,
Cough,
Fatigue (7)
Cough (10)
Weight gain (11)
Days
I
-90
Dyspnea (3)
Edema (12)
II
I
-25
I
I
I
I
-20
I
I
I
I
I
I
-15
I
I
I
I
I I
-10
I
I
I
I I
-5
I
I I I I
0
Admission
I
I
I
I
5
I
I
I
I
I
10
Rapid Assessment of Hemodynamic Status
Congestion at Rest
NO
Low
Perfusion
at Rest
N
O
Y
E
S
YES
Signs/Symptoms of
Congestion:
Orthopnea / PND
JV Distension
Hepatomegaly
Edema
Rales (rare in chronic
heart failure)
Elevated est. PA
systolic( loud P2
and RV lift)
Valsalva square wave
Abdominojugular
reflux
S3
Possible Evidence of Low Perfusion:
Narrow pulse pressure
Cool extremities
Sleepy / obtunded
Hypotension with ACE inhibitor
Low serum sodium
Renal Dysfunction (one cause)
Elevated LFTs
Pulsus alternans
Rapid Assessment of Hemodynamic Status
Congestion at Rest
NO
Low
Perfusion
at Rest
N
O
Y
E
S
Warm
& Dry
YES
Warm &
Wet
67%
Cold &
Dry
5%
Cold &
Wet
28%
Nohria,J Cardiac Failure 2000;6:64
Potential Endpoints of Therapy in ADHF
•
•
•
•
•
•
•
Resting symptoms
JVD
Rales
Edema
PCW or Cardiac Output
BNP
Echo (mitral regurgitation or PA
pressure)
(Drazner M, et al. J Heart Lung Tx 1999;1126. Rosario, et al. JACC 1998;1819-24. Johnson, et
al. Ciruclation 1998 [abstract])
Is the Swan-Ganz Catheter Useful in the
Patient with Acute Decompensated HF?
NO
(Stevenson, et al. JAMA 2005;294:1625-1633)
Early Response of PCW but not CI Predicts
Subsequent Mortality in Advanced Heart Failure
Total Mortality Risk%
Total Mortality Risk%
60
60
50
50
PCW > 16 mmHg
40
30
40
Cardiac Index > 2.6 L/min-M2
30
199
PCW < 16 mmHg
20
20
Cardiac Index < 2.6 L/min/M2
236
10
257
10
P=0.001
0
0
6
12
Months
18
24
0
220
0
6
P=NS
12
Months
18
24
Final hemodynamic measurement in 456 advanced HF patients after tailored vasodilator therapy
(Fonarow G Circulation 1994;90:I-488)
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?
♥
♥
♥
♥
♥
♥
♥
♥
♥
What do these patients look like?
How do you know how much to diurese?
Is BNP useful in judging diuresis?
How to use diuretics
What do you do when the creatinine
increases?
Is ultrafiltration useful?
ACE-inhibitors or beta-blockers first?
Should beta-blockers be started in hospital?
When should you use intravenous therapy?
BNP is Increased with HF and
Systolic or Diastolic Dysfunction
Maisel AS, et al. JACC 2003;41:2010
BNP Levels Pre-discharge Predict Mortality
and Readmisssion
(Logeart D, et al. JACC 20042;40:976-82)
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?
♥
♥
♥
♥
♥
♥
♥
♥
♥
What do these patients look like?
How do you know how much to diurese?
Is BNP useful in judging diuresis?
How to use diuretics
What do you do when the creatinine
increases?
Is ultrafiltration useful?
ACE-inhibitors or beta-blockers first?
Should beta-blockers be started in hospital?
When should you use intravenous therapy?
Sodium Reabsorption Sites in the Nephron
70%
Proximal Tubule
5%
Distal Tubule
Glomerulus
20%
Loop of Henle
Collecting Tubule
Loop
Diuretics
Thiazide
Diuretics
1-4%
Ceiling Doses of Loop Diuretics (mg)
Furosemide bumetanide
torsemicle
IV
po
IV
po
IV
po
moderate
80
80
2-3
2-3
20-50
20-50
severe
200
240
8-10
8-10
50-100
50-100
40
80-160
1
1
10-20
10-20
40-80
160240
2-3
2-3
20-50
20-50
Renal Insufficiency
Cirrhosis with
normal GFR
CHF with normal GFR
(Adapted from Brater C. New Engl J Med 1999)
Bioavailability of Loop Diuretics
100% -
80% -
50% -
10% furosemide
torsemide
bumetanide
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?
♥
♥
♥
♥
♥
♥
♥
♥
♥
What do these patients look like?
How do you know how much to diurese?
Is BNP useful in judging diuresis?
How to use diuretics
What do you do when the creatinine
increases?
Is ultrafiltration useful?
ACE-inhibitors or beta-blockers first?
Should beta-blockers be started in hospital?
When should you use intravenous therapy?
Baseline Renal Dysfunction and Worsening Renal Function
(WRF) are Additive in Predicting Mortality in HF Patients
Predictors of WRF were thiazide
diuretics, increased BUN, and
vascular disease
And a fall in sCr of >
0.3 mg/dL was
associated with
improved mortality
sCreatinine
≤1.2
WRF (>0.3mg/dL) no
1.2-2.0
≥2.0
≤1.2
1.2-2.0
≥2.0
no
no
yes
yes
yes
(de Silva, R. et al. Eur Heart J 2006 27:569-581)
What to do when the creatinine begins to
increase?
• Check volume status
• Check blood pressure (especially at peak
onset of vasodilators)
• Restrict sodium intake (and water if
hyponatremic)
• Check for renal problems (obstructions,
prooteinuria, interstitial nephritis)
• Consider vasodilators or inotropes
• Consider ultrafiltration
Ultrafiltration Improved Weight Loss But
Not Symptoms
End points
Ultrafiltration Diuresis
p
n
83
84
•Weight loss, primary end point 5.0
(mean kg)
3.1
0.001
•Dyspnea score, primary end
point (mean)
6.4
6.1
0.35
•Net fluid loss (mean L)
4.6
3.3
0.001
•K<3.5 mEq/L (%)
1
12
0.018
•Need for vasoactive drugs (%)
3
13
0.015
48 hours
Costanzo MR. American College of Cardiology 2006
Scientific Sessions; March 12, 2006; Atlanta, GA.
Ultrafiltration Decreased Rehospitalization
End points
Ultrafiltration Diuresis
p
90 days
•Rehospitalization (%)
18
32
0.022
•Rehospitalization days (mean)
1.4
3.8
0.022
•Unscheduled office/ED visits (%)
21
44
0.009
Costanzo MR. American College of Cardiology 2006 Scientific
Sessions; March 12, 2006; Atlanta, GA.
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?
♥
♥
♥
♥
♥
♥
♥
♥
♥
What do these patients look like?
How do you know how much to diurese?
Is BNP useful in judging diuresis?
How to use diuretics
What do you do when the creatinine
increases?
Is ultrafiltration useful?
ACE-inhibitors or beta-blockers first?
Should beta-blockers be started in hospital?
When should you use intravenous therapy?
ACE-inhibitor or Beta-blocker First?
CIBIS-III
(Willenheimer R, et al. Circulation 2005;112:2426-2435)
ACE-inhibitor or Beta-blocker First?
CIBIS-III
Bisoprolol first
Enalapril first
(HR 0.94, CI = 077-1.16, = = 0.0.019 for noninferiority)
(Willenheimer R, et al. Circulation 2005;112:2426-2435)
ACE-inhibitor or Beta-blocker First?
CIBIS-III
Bisoprolol first
Enalapril first
Survival
(HR 0.88, CI = 0.63-1.22, p = 0.44)
(Willenheimer R, et al. Circulation 2005;112:2426-2435)
ACE-inhibitor or Beta-blocker First?
CIBIS-III
Enalapril first
Freedom
from
hospitaliz
ation for
worsening
HF
Bisoprolol first
(HR = 1.25, CI = 0.87-1.81, p = 0.23)
(Willenheimer R, et al. Circulation 2005;112:2426-2435)
Current Treatment of Heart Failure
Acutely Decompensated Heart Failure (ADHF)
♥ How to predict mortality?
♥
♥
♥
♥
♥
♥
♥
♥
♥
What do these patients look like?
How do you know how much to diurese?
Is BNP useful in judging diuresis?
How to use diuretics
What do you do when the creatinine
increases?
Is ultrafiltration useful?
ACE-inhibitors or beta-blockers first?
Should beta-blockers be started in hospital?
When should you use intravenous therapy?
Goals in the Treatment of the Patient with
Acutely Decompensated HF
Diuretics
Nesiritide
Milrinone
Improve symptoms
yes (+++)
yes (+)
?
Decrease mortality
?
?(↑)
?(↑)
yes
no
no
?
no
no
yes
no(↑)
no(↑)
Decrease hospitalization
Duration
Repeat hospitalization
Decreased costs