Transcript III - UNC School of Medicine

Acute(ly) Decompensated
Heart Failure
Brian C. Jensen, MD
July 12, 2010
Objectives
Is this heart failure?
How sick is this patient?
What needs to be done now and what can wait until morning?
When do I need to involve my resident?
When do I need to involve the cardiology fellow?
Definition
Heart Failure
a complex clinical
syndrome that
results from the
inability of the
heart to meet the
metabolic demands
of the body
Heart Failure with Preserved Ejection Fraction
?!?
40%
EF > 40 %
EF < 40%
60%
Heart Failure with Preserved Ejection Fraction (HFpEF)
Systolic Dysfunction
Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200
Heart Failure Statistics
5.7 million people have HF
670,000 new cases in 2006
292,000 annual deaths due to HF
1.1 million hospitalizations per year
Largest Medicare expenditure
$37 billion in 2006
AHA Statistical Update: Circulation. 2009;119:e21-e181
Epidemiology of HF
ADHERE
Euro-HF
OPTIMIZE-HF
(n=110 000)
(n=11 000)
(n=48 612)
Mean age, y
75
71
73
Women (%)
52
47
52
Known heart failure (%)
75
65
87
Preserved EF (%)
40
54
49
CHD
57
68
50
Hypertension
72
53
71
Diabetes
44
27
42
Atrial fibrillation
31
43
31
Renal insufficiency
30
17
30
COPD
31
...
28
Demographic characteristics
Medical history (%)
Gheorghiade M, et al. Circulation 2005;112:3958-68
Causes of Heart Failure
Coronary Artery Disease: Dead Meat Don’t Beat
Causes of Heart Failure
Cardiomyopathy
Felker, GM et al. N Engl J Med 2000;342: 1077-84
Nomenclature
Stage vs. Class
ACC-AHA Stage
NYHA Functional Class
A At high risk for HF but without
structural heart disease or symptoms
of HF (e.g. patients with hypertension
or CAD)
B Structural heart disease but without
symptoms of HF
I Asymptomatic
II Symptomatic with moderate exertion
C Structural heart disease with prior or
current symptoms of HF
III Symptomatic with minimal exertion
D Refractory HF requiring specialized
IV Symptomatic at rest
interventions
Adapted from: Farrell MH, Foody JM, Krumholz HM. JAMA 2002;287:890
Classification of Recommendations and
Level of Evidence
Class I
Class IIa
Class IIb
Class III
Benefit >>> Risk
Benefit >> Risk
Additional studies with
focused objectives
needed
Benefit ≥ Risk
Additional studies with
broad objectives needed;
Additional registry data
would be helpful
Risk ≥ Benefit
No additional studies
needed
Procedure/ Treatment
SHOULD be
performed/
administered
IT IS REASONABLE to
perform
procedure/administer
treatment
Procedure/Treatment
MAY BE CONSIDERED
Level A:
Data derived from multiple randomized clinical trials or meta-analyses
Multiple populations evaluated
Level B:
Data derived from a single randomized trial or nonrandomized studies
Limited populations evaluated
Level C:
Only consensus of experts opinion, case studies, or standard of care
Very limited populations evaluated
Procedure/Treatment
should NOT be
performed/administered
SINCE IT IS NOT HELPFUL
AND MAY BE HARMFUL
Heart Failure is Progressive
Prognosis in Advanced Heart Failure
Unchanged in 20 years
Stage D, NYHA Class IV
Acute cardiogenic shock
End organ dysfunction
50% Mortality
Imminent
1 month
Inotrope-dependent
ACE-inhibitor intolerant
Cachexia, hyponatremia, CKD
3-6 months
6 months
6-12 months
Tolerating oral therapies
Stabilized to NYHA Class III
± 12 months
> 24 months
Stevenson LW, Rose EA. Circulation 2003;108:3059
Heart Failure in Context
One Year Mortality
90
80
1 Year Mortality (%)
70
60
50
40
30
20
10
0
AIDS
Leukemia
Lung Cancer
Diagnosis
Pancreatic Cancer End-stage HF with
Optimal Medical
Management
Rose EA, et al. N Engl J Med. 2001 Nov 15;345(20):1435-43.
It’s 2:30 a.m.
You’re paged to the ED to see this guy…
EVALUATION
Diagnosis
Modified Framingham Clinical Criteria
MAJOR
MINOR
Paroxysmal Nocturnal Dsypnea (PND)
Bilateral leg edema
Orthopnea
Nocturnal cough
Elevated jugular venous pressure (JVD)
Dyspnea on ordinary exertion
Pulmonary rales
Hepatomegaly
Third heart sound (gallop)
Pleural effusion
Cardiomegaly on chest x-ray
Tachycardia > 120 bpm
Pulmonary edema on chest x-ray
Weight loss > 4.5 kg in 5 days
Diuresis > 4.5 kg in 5 days
Diagnosis requires 2 major or 1 major and 2 minor criteria
McKee PA et al N Engl J Med 1971; 85:1441
“Left” and “Right” Heart Failure
Distended Jugular Veins
elevated right atrial pressure
Hepatomegaly
elevated IVC pressure
Pulmonary rales (“crackles”)
elevated capillary pressure
S3 or S4 gallop
increased LV pressure,
decreased compliance
Orthopnea
Peripheral Edema
elevated capillary bed pressure
increased venous return
Evaluation of Heart Failure
EKG
Q waves, LVH, heart block, tachyarrhythmia
CXR
pulmonary edema, other causes of dyspnea
Blood tests
Chemistry panel: renal function, sodium, glucose
Liver function tests
TnI
BNP
Echocardiogram
Function (systolic and diastolic) ?
Structure (LVH, dilation, valves, shunts)
Cardiac catheterization?
“Left heart cath” and/or right heart cath
Decompensated Heart Failure
Why?
I IIa IIb III
Precipitating Factors for Acute HF
It is recommended that the following common
potential precipitating factors for acute HF be
identified as recognition of these comorbidities is
critical to guide therapy:
• acute coronary syndromes/coronary ischemia
• severe hypertension
• atrial and ventricular arrhythmias
• infections
• pulmonary emboli
• renal failure
• medical or dietary noncompliance
New
Predictors of
In-Hospital
Mortality
BUN > 43
SBP < 115
Creatinine > 2.75
Copyright restrictions may apply.
ADHERE. JAMA 2005; 293:572-80
Acute Decompensated Heart Failure
Signs and Symptoms
CARDIAC OUTPUT
“WET”
Dyspnea, orthopnea, PND,
morning cough, peripheral
edema, rales, ascites,
hepatic congestion, jugular
venous distention
“COLD”
Nausea, early satiety, altered mental status, acidosis,
worsening renal or hepatic function, reduced capillary refill,
cold skin, hypotension, narrow pulse pressure
PULMONARY CAPILLARY WEDGE PRESSURE
Inpatient Triage
CARDIAC OUTPUT
Decompensated Heart Failure
WARM AND DRY
WARM AND WET
Compensated
Congested
Optimize oral therapy
Diuretics
Outpatient
ED or Inpatient
COLD AND DRY
COLD AND WET
Low Flow State
Decompensated
Inotropes, vasodilators, ?IABP
Diuretics, vasodilators, inotropes
ICU
ICU
PULMONARY CAPILLARY WEDGE PRESSURE
Adapted from Nohria,J Cardiac Failure 2000;6:64
Who’s Cold?
Proportional Pulse Pressure
Pulse Pressure
Systolic BP- Diastolic BP
Proportional Pulse Pressure
Pulse Pressure
Systolic BP
Proportional Pulse Pressure ≤ 25% predicts Cardiac Index ≤ 2.2
Sensitivity 91%
Specificity 83%
Stevenson LW and Perloff JK. JAMA 1989;261(6):884-8
Who’s Wet?
How well does physical exam predict PCWP > 22 mmHg?
Finding
JVP > 11cm
Edema > trace
Increased apical P2
Rales
Hepatomegaly
S3 gallop
Valsalva square root sign
Sensitivity
67%
48%
37%
15%
15%
63%
13%
Specificity
74%
69%
75%
85%
92%
40%
96%
Stevenson LW and Perloff JK. JAMA 1989;261(6):884-8
Measurement of BNP
I IIa IIb III
Measurement of natriuretic peptides (B-type
natriuretic peptide (BNP) or N-terminal pro-B-type
natriuretic peptide (NT-proNBP) can be useful in the
evaluation of patients presenting in the urgent care
setting in whom the clinical diagnosis of HF is
uncertain. Measurement of natriuretic peptides (BNP
and NT-proBNP) can be helpful in risk stratification.
Modified
The value of serial measurements of BNP to guide
therapy for patients with HF is not well established.
NO CHANGE
BNP is Increased with Heart Failure
Irrespective of Ejection Fraction
Maisel AS, et al. JACC 2003;41:2010
BNP Levels Have Prognostic Value
Direct correlation with mortality and readmission rate
Logeart D, et al. JACC 20042;40:976-82
NT-pro BNP
Too Scarred for Battle?
Younger (< 75)
All Ages
BNP guided
“Intensive Care”
Usual Care
Older (> 75)
BATTLESCARRED: J Am Coll Cardiol, 2010; 55:53-60
Invasive Hemodynamic Monitoring (?)
I IIa IIb III
Invasive hemodynamic monitoring can be useful for
carefully selected patients with acute HF who have
persistent symptoms despite empiric adjustment of
standard therapies, and
New
a. whose fluid status, perfusion, or systemic or
pulmonary vascular resistances are uncertain;
b. whose systolic pressure remains low, or is associated
with symptoms, despite initial therapy;
c. whose renal function is worsening with therapy;
d. who require parenteral vasoactive agents; or
e. who may need consideration for advanced device
therapy or transplantation.
Invasive Hemodynamic Monitoring
ESCAPE
META-ANALYSIS
ESCAPE
ESCAPE: JAMA 2005;294:1625-1633
Shah MR et al, JAMA 2005;294(13):1664-1670
MANAGEMENT
How Much Diuretic Should I Give?
…Enough
Sodium Excretion Rate
Maximal Response
Threshold
Loop Diuretic Dose
Ceiling Doses of Loop Diuretics
FUROSEMIDE
BUMETANIDE
TORSEMIDE
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
Cirrhosis (normal GFR)
40
80-160
1
1
10-20
10-20
CHF (normal GFR)
40-80
160-240
2-3
2-3
20-50
20-50
Renal Insufficiency
Adapted from Brater C. New Engl J Med 1999
What to do when the creatinine rises
Hint: it’s always “pre-renal”
 Check volume status
 Orthostatics, skin turgor, mucous membranes
 Check blood pressure (especially at peak onset of vasodilators)
 Restrict sodium intake (and water if hyponatremic)
 Check for intrinsic renal problems
 U/A with sediment
 Consider vasodilators or inotropes
 Consider ultrafiltration
Intensifying the Diuretic Regimen
Chicken or egg?
When diuresis is inadequate to relieve congestion, as evidence by
clinical evaluation, the diuretic regimen should be intensified using
either:
a. higher doses of loop diuretics;
b. addition of a second diuretic (such as metolazone,
New
spironolactone or intravenous chlorthiazide) or
c. Continuous infusion of a loop diuretic.
DIG Trial Substudy (Chicken)
Prospective Observational
Study (Egg)
Stable
Unstable
Ahmed A et al. Int J Cardiol 2007; 125(2):246-53
Mielniczuk LM et al. J Card Fail 2008;14:388-93
Vasodilator Therapy
I IIa IIb III
In patients with evidence of severely
symptomatic fluid overload in the absence of
systemic hypotension, vasodilators such as
intravenous nitroglycerin, nitroprusside or
neseritide can be beneficial when added to
diuretics and/or in those who do not respond to
diuretics alone.
New
Vasodilator Therapy
Nipride: A Challenge
MORTALITY
Retrospective anaylsis (n = 175)
ADHF with Cardiac Index < 2.0
NIPRIDE
RR = 0.54
NO NIPRIDE
Mullens W et al. J Am Coll Cardiol 2008;52:200–7
Vasodilator Therapy
Nesiritide: Good, Bad, or irrelevant?
FUSION-II (RCT n = 911)
1. ACC/AHA Stage C/D
Outpatient Nesiritide vs. Placebo
EVENT-FREE
SURVIVAL
RENAL FAILURE
BNP-CARDS (RCT n=75)
1. ADHF
2. CRI
Nesiritide vs. Placebo
BNP-CARDS: Witteles RM et al. JACC 50(19) 1835-40
FUSION-II: Yancy CW et al. Circ: Heart Failure. 2008;1:9-16
Inotropes
Dobutamine
Milrinone
Kass DA. Nature Medicine 2009; (15): 24 – 25
Inotropes
…are not “pressors”
DRUG
Dobutamine
SV
+++
HR
++
SVR
+/-
BP
+/-
Milrinone
Dopamine*
+++
+
+ (SVT)
++
++
++
*assuming moderate dose (2 – 5 mcg/kg/min)
Felker GM, O’Connor CM. Am Heart J 2001;142:393-401
Infusion of Positive Inotropic Drugs
I IIa IIb III
OPTIME-CHF, etc.
Routine intermittent infusions of vasoactive and positive inotropic agents are
not recommended for patients with refractory end-stage HF.
Modified
I IIa IIb III
Use of parenteral inotropes in normotensive patients with acute decompensated
HF without evidence of decreased organ perfusion is not recommended.
OPTIME-CHF (RCT n = 951)
ADHF not requiring inotrope
Milrinone (500 mcg/kg/min) vs. Placebo
New
OPTIME-CHF: Cuffe, Califf, Adams KF et al. JAMA 2002; 287(12):1541
Digoxin: the only “inotrope” with data
DIG Trial
Total mortality
p=NS
HF Mortality
p=0.06
N Engl J Med 1997;336:525-33
Digoxin: the only “inotrope” with data
Death or HF Hospitalization
DIG Trial
PLACEBO
RR 0.75
p < 0.001
DIGOXIN
Time (Months)
N Engl J Med 1997;336:525-33
Summary of HF Pharmacotherapy
SAVE LIVES
ACE inhibitors/ARBs
Beta blockers
Hydralazine/Nitrates
Aldosterone inhibitors
IMPROVE SYMPTOMS
Diuretics
Digoxin
Inotropes
TNG, nipride, nesiritide
DISCHARGE
Reconciling and Adjusting Medications
OPTIMIZE-HF and B-CONVINCED: Don’t Stop the b-Blockers
In patients with reduced ejection fraction experiencing a symptomatic
exacerbation of HF requiring hospitalization during chronic maintenance
treatment with oral therapies known to improve outcomes, particularly ACE
inhibitors or ARBs and beta-blocker therapy, it is recommended that these
therapies be continued in most patients in the absence of hemodynamic
instability or contraindications.
New
OPTIMIZE-HF (n = 5791)
1. Admitted with HF
2. Pre-specified follow-up
Death or hospitalization
MORTALITY
WITHDRAWN
NOT TREATED
CONTINUED
NEWLY STARTED
DAYS SINCE DISCHARGE
HR death = 2.3
OPTIMIZE-HF substudy: Fonarow GC et al. JACC 2008; 52(3) 190-199
Can We Wait to Start the Beta-Blockers?
Freedom from Death and Rehospitalization
IMPACT - HF
Pre-discharge
Post-discharge
Days Since Randomization
Galtis WA, et al. JACC 2004;43:1534
ACE-inhibitor or Beta-blocker First?
CIBIS-III
Event-free Survival
(HR 0.94 (077-1.16), p= 0.0.019 for non-inferiority
Bisoprolol first
Enalapril first
Time (months)
Willenheimer R, et al. Circulation 2005;112:2426-2435
“Optimal Medical Management”
The Neurohormonal Component
ACE-inhibitor
Enalapril (Vasotec)
Captopril (Capoten)
Ramipril (Altace)
Lisinopril (Prinivil, Zestril)
Trandolapril (Mavik)
Quinapril (Accupril)
10 mg bid
50 mg tid
5 mg bid
20 mg qd
4 mg qd
20-40 mg bid
b-Blocker
Carvedilol (Coreg)
Metoprolol XL/CR (Toprol XL)
25-50 mg bid
200 mg qd
Bisoprolol (Zebeta)
10 mg qd
Seattle Heart Failure Mode
http://depts.washington.edu/shfm/app.phpl
Effective Outpatient Care
Begins with an Inpatient
I IIa IIb III
Post-discharge systems of care, if available, should be used to
facilitate the transition to effective outpatient care for patients
hospitalized with HF.
New
Euro Heart Failure Survey (n = 3261)
Interview 12-weeks after discharge
Recall…
46%
Implementation… 67%
Core Measures
UNCH
 EF assessment
 ACEi/ARB (LVEF <40%)
 BB (LVEF <40%)
 Smoking cessation
 Discharge Instructions
o
o
o
o
o
o
Activity
Diet
Follow Up
Medications
Symptoms Worsening
Daily Weights and “Rule of 2’s”
Referral for Refractory End-Stage HF
We are here to help
Referral for cardiac transplantation in potentially eligible
patients is recommended for patients with refractory
end-stage HF.
NO CHANGE
I IIa IIb III
Referral of patients with refractory end-stage HF to
an HF program with expertise in the management
of refractory HF is useful.
NO CHANGE
UNC Heart Failure Team
Cardiology (919-843-5214)
Patty Chang, MD MHS
Kirkwood Adams, MD
Carla Sueta Dupree, MD PhD
Brian Jensen, MD
Cardiothoracic Surgery (919-966-3381)
Brett Sheridan, MD
Michael Bowdish, MD
Michael Mill, MD
Transplant Coordinators
Scott Kowalczyk, RN BSN CTCC
Katie McMahon, RN BSN
VAD Coordinator
Mandy Bowen, RN BSN
Diagnosis
Echocardiogram
Normal
Dilated Cardiomyopathy
The Hemodynamic or “Mechanical” Paradigm
The Cardiovascular system as “Pump and Pipes”
6
1
4
=
https://www.clevelandclinic.org/heartcenter/images/guide/heartworks/heart_bloodvessels.jpg
The Hemodynamic or “Mechanical” Paradigm
Heart Failure Defined by Weights and Measures
Neurohormonal Paradigm
The Starting Lineup
Renin
Converts angiotensinogen to angiotensin I
Angiotensin I
vasoconstriction, cardiomyocyte hypertrophy,
aldosterone and vasopressin release, thirst
ACE
Angiotensin II
Aldosterone
Norepinephrine
sodium retention, cardiac fibrosis
chronotropy, inotropy, vasoconstriction,
renin secretion
Other players: Endothelin, Vasopressin, ANP, BNP, etc
Neurohormonal Paradigm
In Context
Norepinephrine
http://www.cvphysiology.com/Blood%20Pressure/BP015.htm
Ejection Fraction
Compensatory
Mechanisms
60 %
Secondary
Damage
20 %
Time (yrs)
Asymptomatic
Symptomatic
Mann, Circulation 1999; 100: 999-1008
Sympathetic Activation in Heart Failure
“Fight or Flight” in the brain, heart and kidneys
CNS sympathetic outflow
 Cardiac sympathetic
activity
b-Blockers
Renal and vascular
sympathetic activity
b-adrenergic
receptors
b-AR
Myocardial toxicity
Increased arrhythmias
Decrease Salt and
Water Intake
Activation
of RAS
a1-AR
Vasoconstriction
Sodium retention
Disease progression
Adapted from Packer M. Progr Cardiovasc Dis. 1998;39(Supp I):39-52
Renin-Angiotensin System
Friend and Foe
ACE inhibitors
ARBs
Aldosterone
antagonists
http://en.wikipedia.org/wiki/File:Renin-angiotensin-aldosterone_system.png
Neurohormonal Antagonists
Why we do what we do
Events prevented per 1000 patient-hours of treatment
Hospitalizations
Prevented
Deaths prevented
ACE-inhibitor
99
13
SOLVD
Beta-blocker
65
38
MERIT-HF
Spironolactone
138
57
RALES
Digoxin
40
0
DIG
Therapy
Evidence
Adapted from: Remme WJ et al. Eur. Heart J. 2001;22:1527-1560.
Neurohormonal Blockade
The Foundation
I IIa IIb III
I IIa IIb III
Angiotensin-converting enzyme (ACE) inhibitors are
recommended for all patients with current or prior
symptoms of HF and reduced LVEF, unless
contraindicated .
NO CHANGE
Use of 1 of the 3 beta blockers proven to reduce mortality
(i.e., bisoprolol, carvedilol, and sustained release
metoprolol succinate) is recommended for all stable
patients with current or prior symptoms of HF and
reduced LVEF, unless contraindicated.
Modified
Hydralazine and Nitrates
A-HeFT
I IIa IIb III
The combination of hydralazine and nitrates is recommended to improve
outcomes for patients self-described as African-Americans, with
moderate-severe symptoms on optimal therapy with ACE inhibitors, beta
blockers, and diuretics.
New
Bidil
Placebo
Aldosterone antagonists
Benefits and risks
I IIa IIb III
Addition of an aldosterone antagonist is recommended in selected patients
with moderately severe to severe symptoms of HF and reduced LVEF who
can be carefully monitored for preserved renal function and normal
potassium concentration. Creatinine 2.5 mg/dL or less in men or 2.0 mg/dL
or less in women and potassium should be less than 5.0 mEq/L. Under
circumstances where monitoring for hyperkalemia or renal dysfunction is not
anticipated to be feasible, the risks may outweigh the benefits of aldosterone
antagonists.
NO CHANGE
RR death = 0.70
RALES
Class (III-)IV
RR death = 0.85
EPHESUS
HF post MI
EPHESUS: Pitt B, et al. N Engl J Med 2003; 348(14):1309-21
RALES: Pitt B, et al. N Engl J Med 1999; 341(10):709-17
ACE-inhibitor or Beta-blocker First?
CIBIS-III
(Willenheimer R, et al. Circulation 2005;112:2426-2435)
The Guidelines
Outpatient Management
Jessup M, Brozena S. NEJM 2003;348:2007
I IIa IIb III
HeartMate II
Jarvik 2000
Ventricular Assist Devices
Consideration of an left ventricular assist device as permanent or
“destination” therapy is reasonable in highly selected patients with
refractory end-stage HF and an estimated 1-year mortality over 50% with
medical therapy.
NO CHANGE