Transcript Congestion in Heart Failure - Open Secret Communications

Congestion in Heart Failure
Mihai Gheorghiade, MD
Professor of Medicine
Northwestern University
Feinberg School of Medicine
Chicago, Illinois
Congestion in HF
Definitions
2
Congestion in Heart Failure (HF)
Clinical congestion: symptoms (dyspnea) and signs
(JVD, rales, edema)
Hemodynamic or cardiopulmonary congestion: high
LV filling pressures with or without clinical congestion
JVD, jugular venous distention; LV, left ventricular.
3
Hemodynamic Congestion
Often Does Not Translate
into Signs/Symptoms of HF
4
Hemodynamic Congestion Often Does
Not Translate in Signs/Symptoms
 Among patients with severe heart failure1
– PCWP 33 ± 6 mm Hg, CI 1.8 ± 0.5, LVEF 0.18 ± 0.06
– CXR: 27% no congestion, 41% minimal congestion
 Among patients with moderate to severe heart failure2
– PCWP 30 ± 9 mm Hg, CI 2.1 ± 0.8, LVEF 0.18 ± 0.06
– No rales: 84%, no edema: 80%, no JVP 50%,
no orthopnea: 22%
 Cardiopulmonary congestion may not be recognized
clinically (doesn’t translate into symptoms/signs until late)
CXR, chest X-ray; LVEF, left ventricular ejection fraction.
1 Mahdyoon H, et al. Am J Card. 2003;63:625-627.
2 Stevenson LW, et al. JAMA. 1989;261:884-888.
5
Both Patients Have High PCWP
• Radiographic congestion and CTR often does not correlate with PCWP
PCWP, pulmonary capillary wedge pressure; CTR, cardiothoracic ratio.
Kono T, et al. Jpn Circ J. 1992;56:359-365.
6
Symptoms and Signs: The Tip
of the Congestion Iceberg in HF
S
Y
M
P
T
O
M
S
Systemic
congestion
(JVD, edema)
 Hydrostatic
pressure
 Oncotic pressure
 Permeability
Lymphatic drainage
capacity
Alveolar-capillary
membrane integrity
Abnormal lung function
Respiratory muscle dysfunction
Other factors
 RV + RA pressure
Dyspnea
Increase PA pressure
Increased PCWP (congestion)
 LA and LV diastolic pressure
LVDP + impaired volume regulation
Alveolar edema
Redistribution in
pulmonary vascular bed
+ interstitial edema
Mitral
regurgitation
Abnormal LV function (systolic and/or diastolic)
RV, right ventricular; RA, right atrial; PA, pulmonary artery; LA, left atrial; LVDP, left ventricular diastolic pressure.
7
Absence of Specific Signs, Symptoms and
CXR Findings Doesn’t Exclude High PCWP
•
Ability to predict PCWP >18-20 mm Hg in patients with severe heart failure
Dyspnea on exertion
Orthopnea
Edema
JVD
S3
CXR
Cardiomegaly
Redistribution
Interstitial edema
Pleural effusion
Sens.
Spec.
66
66
46
70
73
97
60
60
43
PPV, positive predictive value; NPV, negative predictive value.
Adapted from Chakko S, et al. Am J Med. 1991;90:353-359.
Adapted from Butman SM, et al. J Am Coll Cardiol. 1993;22:968-974.
PPV
NPV
52
47
73
79
42
45
61
79
85
66
27
37
46
62
44
10
68
73
79
61
75
78
76
--52
53
47
8
Importance of Recognizing
Congestion Early
 Identifying hemodynamic congestion early will lead
to early treatment, and prevent hospitalizations and
possibly progression of heart failure
9
Congestion Is the Main Reason
for Heart Failure Hospital
Admissions and Readmissions
10
Acute Heart Failure Syndromes
(AHFS) Epidemiology (US)
 1 million admissions per year with the primary
diagnosis of heart failure (HF)
 3,000,000 admissions per year with
primary or secondary diagnosis of HF
 Post-discharge event rate (readmissions/death):
35% at 60 days
Gheorghiade M, et al. Circulation. 2005;112:3958-3968.
11
AHFS: Hospitalizations
 Worsening chronic HF (80%)
 Acute de novo heart failure
(diagnosed for the first time) (15%)
 Advanced/end-stage/refractory HF (5%)
Gheorghiade M, et al. Circulation. 2005;112:3958-3968.
12
Clinical Presentation of Patients
Hospitalized with Heart Failure
(200,000 patients)
Any dyspnea (%)
89
Dyspnea at rest (%)
34
Fatigue (%)
32
Rales (%)
68
Peripheral edema (%)
66
Initial CXR assessed (%)
91
Chest X-ray congestion (%)
75
Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.
Cleland JG, et al. Eur Heart J. 2003;24:442-463.
13
Congestion, Not Low Cardiac Output:
Main Finding in Hospitalized Patients
SBP >140 mm Hg1
SBP 90-140 mm Hg1
SBP <90 mm Hg1
50%
48%
2%
Mean heart rate (bpm)2
 90
PCWP (mm Hg)2
25-30
Cardiac index2
usually preserved
1 Fonarow
2
GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.
The VMAC Investigators. JAMA. 2002;287:1531-1540.
14
Outcomes
ADHERE
EURO HF
(150,000 pts) (11,327 pts)
> 2.5 kg weight loss (%)
50
N/A
OPTIMIZE-HF
(50,000 pts)
50
HF Symptoms
Unchanged/worse
Better (symptomatic)
Better (asymptomatic)
Length of stay (days)
In-hospital mortality (%)
Mortality at 2-3 mos (%)
Readmissions at 2-3 mos (%)
<1
40
50
4.3 (3, 7)
4
N/A
N/A
Adams KF, et al. Am Heart J. 2005;149:209-216.
Cleland JGF, et al. Eur Heart J. 2003;24:442-463.
Fonarow GC, et al. J Am Coll Cardiol. 2005; oral presentation 844-4.
<3
40
51
11
7
6.5
24
4 (3, 7)
4
9
31
15
Patients (%)
More Than 50% of Patients Have Little or
No Weight Loss During Hospitalization
35
30
25
20
15
10
5
0
33%
24%
13%
7%
15%
6%
3%
(<-20)
(-20 to -15)(-15 to -10) (-10 to -5)
(-5 to 0)
(0 to 5)
(5 to 10)
2%
(>10)
Change in Weight (lbs)
Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.
16
Change in Heart Failure Signs and
Symptoms (Admission to Discharge)
Admission
Discharge
79
42
50
33
53
58
5
12
4
57
33
57
20
50
6
13
6
13
Symptoms (%)
Dyspnea on exertion
Dyspnea at rest
Orthopnea
PND
Fatigue
Signs (%)
JVP > 6 cm
Rales
S3 gallop
Edema >2+
PND, paroxysmal nocturnal dyspnea.
Gattis WA, et al. J Am Coll Cardiol. 2004;43:1534-1541.
17
Hospitalizations for Heart Failure
 Clinical congestion is the primary reason for HF
admissions
 Low cardiac output and associated signs/symptoms
are uncommon
 Suboptimal weight reduction during hospitalization
 Although appearing improved clinically, many
patients are discharged with signs and symptoms
(related to hemodynamic congestion that is not
being identified clinically)
18
Congestion and Prognosis
in Heart Failure
19
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
1
Event-free survival
Event-free survival
JVD & S3* Predict
Hospitalization/Death
No S3
P<0.001
0
250
S3
500
750
1000
1250
1500
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
No JVP
P<0.001
JVP
0
250
750
1000
1250
1500
Days
Days
Endpoint
500
Elevated JVP
S3
Elevated JVP and S3
All-cause mortality
1.15 (0.95-1.38)
1.15 (0.99-1.33)
1.17 (1.02-1.35)
HF hospitalization
1.32 (1.08-1.62)
1.42 (1.21-1.66)
1.43 (1.23-1.66)
*Difficult to assess clinically.
Drazner MH, et al. N Engl J Med. 2001;345:574-581.
20
High PCWP at Hospital Discharge Is
Associated with Higher Long-Term Mortality
60
60
Mortality (%)
Mortality (%)
50
50
PCWP >16 mmHg
N=199
40
40
P=0.001
30
20
30
10
10
0
0
6
12
18
Time (months)
Fonarow GC, et al. Circulation. 1994;90:I-488.
P=NS
20
PCWP ≤16 mmHg
N=257
0
CI >2.6 L/min/m2
N=236
24
0
6
CI ≤2.6 L/min/m2
N=220
12
18
Time (months)
24
21
Post-discharge Freedom from Congestion
Is Associated with Better Prognosis
100
No congestion (N=80)
Survival (%)
80
1-2 congestion (N=40)
60
P<0.001
40
3-5 congestion (N=26)
20
Reassess at 4-6 weeks
0
0
6
12
18
Months after reassess
24
Criteria for congestion: Orthopnea, JVD, weight gain ≥2 lb in a week, need
(0-5)
to increase diuretic dose, leg edema
Lucas C, et al. Am Heart J. 2000;140:840-847.
22
High PCWP: Important Independent
Predictor for Survival
 In the ESCAPE trial, PCWP and not cardiac output
was a significant predictor of subsequent survival
 Other independent predictors of survival:
– Systolic blood pressure <120 mm Hg
– Distance walked in 6 minutes
– Blood urea nitrogen
ESCAPE Investigators. Presented at the 77th American Heart Association Scientific Sessions.
Late Breaking Clinical Trials Session. New Orleans, LA. 11/10/2004.
23
Pathophysiology
of Congestion
Way congestion develops?
What are the consequences?
24
Why Do Patients With HF
Develop Congestion?
Heart
 Cardiac pump function/loading conditions (diastolic failure)
Kidney
 Sodium and water handling (retention/edema)
Neurohormonal abnormalities
 Modulates cardiac and renal function
– eg, excess vasopressin ≥ hyponatremia, water retention
All 3 need to be abnormal in order to have significant congestion
25
The Cardiorenal Syndrome
in Heart Failure
Decreased cardiac output
Decreased cardiac
performance
Increased water
& Na+ retention
(Congestion)
Impaired renal
function
Modified from Abraham WT.
Neurohormonal
activation
Increased
venous pressure
Diminished
blood flow
Decreased renal
perfusion
26
Effect of Increasing Central
Venous Pressure (CVP) on GFR in
Intact Dogs with Constant BP
1.4
Raised venous
pressure:
A direct cause
of renal sodium
retention
GFR (ml/min)
P<.05
1.1
P<.05
0.8
High CVP significantly
impairs GFR
0.5
0
0
6.25
2
12
GFR, glomerular filtration rate; BP, blood pressure.
Firth JD et al. Lancet. 1988;1(8593):1033-1035.
18.75
4 Hg
mm
25
0
6
Central Venous Pressure
8
27
Congestion May Contribute
to the Progression of Heart
Failure in Patients
Admitted With HF
28
Progression of Heart Failure
Coronary artery
disease
Hypertension
Arrhythmia
Left ventricular
injury
Pathologic
Remodeling
Low ejection
fraction
Death
Cardiomyopathy
Pump
failure
Valvular disease
• Neurohormonal
stimulation
• Endothelial
dysfunction
• Vasoconstriction
• Renal sodium
retention
Cohn J. N Engl J Med. 1996;335:490-498.
Symptoms:
Dyspnea
Fatigue
Edema
Chronic
heart
failure
29
Severe Congestion (PCWP/LVDP)
in Heart Failure* –
Potential Deleterious Effects
 Subendocardial ischemia/cell death by necrosis/apoptosis1
 Changes in extracellular matrix structure and function1
 Changes in LV shape:
– Increased afterload
– Leads to mitral regurgitation
 Impaired cardiac venous drainage from coronary veins
(diastolic dysfunction)
 Lower threshold for arrhythmias
 Progression of LV dysfunction/remodeling
*The number of patients with congestion will probably increase due to a decrease in the rate of sudden death
(beta-blockers, ICD).
1Gheorghiade M, et al. Circulation. 2005;112:3958-3968.
30
Myocardial Injury in AHFS
Hemodynamic deterioration
(eg, fluid overload)

Myocardial injury (Tn release)

Progression of heart failure
Tn, serum troponin.
.
Gheorghiade M, et al. Circulation. 2005;112:3958-3968
31
Pilot Randomized Study of Nesiritide vs
Dobutamine in Heart Failure
(PRESERVD-HF) Patients with CAD
 At the time of admission for HF, elevations of TnT
and TnI are present in 43% and 74% of patients
 During hospitalizations, among those without
elevated Tn at baseline, 42% of patients will release
TnI and 8% of patients will release TnT
 TnT/I correlated with short term outcomes
TnT, troponin T; TnI, troponin I.
Gheorghiade M, et al. Am J Cardiol. 2005;96(6A).
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AHFS: Prognostic Value of Tn T
1
0.9
TnT <0.1 ng/mL (N=46)
0.8
Survival
0.7
0.6
TnT >0.1 ng/mL (N=32)
0.5
0.4
0.3
0.2
0.1
0
3
6
9
12
15 18
21
24 27
30 33
36
Months
Perna ER, et al. Am Heart J. 2002;143:814-820.
33
Acute Exacerbations May Contribute
to the Progression of Heart Failure
Cardiac Function
With each event, myocardial injury may
contribute to progressive LV dysfunction
Acute event

Death
Time
Gheorghiade M, et al. Am J Cardiol. 2005;96(6A-11A).
34
ESCAPE
%
Trial Design: ESCAPE was a randomized study of pulmonary artery catheter (PAC) guided therapy (n=215)
vs clinical assessment alone (n=218) among patients hospitalized with recurrent heart failure but without an
established need for a PAC. Primary endpoint was days neither dead nor hospitalized through 6 months.
Results
Rehospitalization
Death
 Study population had severe illness (mean
by 6 months
by 6 months
LVEF 20% and mean SBP 105.6 mm Hg)
P=NS
P=NS
 Trial discontinued early by DSMB due to lack
25
3
of efficacy
 No difference between groups in primary
20
endpoint of days neither dead nor hospitalized
through 6 months (HR 1.00; 95% CI 0.83-1.21
2
 Also no difference in frequency of
15
rehospitalization or death (Figure)
 Both groups had improvements in exercise and
quality of life endpoints, with non-significant
10
trend for larger improvement in PAC group
1
Conclusions
 Among patients hospitalized with recurrent
5
heart failure but without an established need
for a PAC, use of PAC to guide therapy was
not associated with a reduction in days neither
0
0
dead nor hospitalized compared with clinical
PAC
Control
assessment alone
SBP, systolic blood pressure.
 Data cannot be extrapolated to patients that do
Presented at AHA Scientific Sessions 2004.
have indication for PAC guided therapy
www.cardiosource.com
35
Mortality at 6 Months in Patients
Admitted with HF in the ESCAPE Trial
35
Mortality
30
25
%
20
15
10
5
0
NA:
121-134
135-136
137-139
140-147 mEq/dL
CI
1.8 2.3
1.9  1.2
2.1  2.1
1.9  2.1
PCWP
27  19
22  18
25  15
22  17
RAP
15  9
12  8
12  8
98
CI, cardiac index; RAP, right atrial pressure.
Gheorghiade M, et al. Presented at ACC, 2005.
36
Rapid and Substantial vs Gradual and
Modest Hemodynamic Improvement
 In patients hospitalized for HF, normalization of
markedly abnormal hemodynamics with high doses
of diuretics, vasodilators and/or inotropes was
associated with an increase in post-discharge
mortality and hospitalizations (ESCAPE)
 In outpatients with HF, hemodynamic improvement
appears to prevent hospitalizations in class III but not
IV patients (COMPASS)
37
Hospitalizations for Heart Failure:
Congestion Precedes Hospitalization
Pressure Change
Hospitalization
40
Percent Change
RV Systolic Pressure
Estimated PA Diastolic Pressure
30
Heart Rate
20
10
0
-10
Baseline
-7
-6
-5
-4
-3
-2
-1
Recovery
Days Relative to the Event
Adamson PB, et al. J Am Coll Cardiol. 2003;41:565-571.
38
Congestion in HF: Conclusions
 Congestion is an important predictor of mortality
and morbidity
 Congestion is the primary cause of HF hospital
admissions and predicts readmissions
 Hemodynamic congestion is often difficult to
recognize, delaying appropriate interventions
 Clinical congestion often lags behind hemodynamic
congestion
 Congestion may contribute to the progression of HF
39
Hemodynamic Congestion
 Hemodynamic or cardiopulmonary congestion (elevated PCWP)
starts days or weeks prior to hospitalization
 May occur in the absence of signs (rales, JVD, edema) or
symptoms of clinical congestion
 Early treatment of hemodynamic congestion
may prevent hospitalization and progression
of heart failure
 Improved methods of monitoring hemodynamic congestion may
improve clinical management
and outcomes
40
Why Prevent Hospitalizations*?
 Prevent possible myocardial injury
(progression of HF)
 Once the patient is hospitalized, we're forced to use
interventions (eg, inotropic agents) that may cause
myocardial injury
 High post-discharge mortality and hospitalizations
 Cost
*The most important predictor of prognosis.
Gheorghiade M, et al. Circulation. 2005;112:3958-3968.
41
ACC/AHA HF Performance
Measures: Outpatient
 Initial laboratory tests
 Left ventricular systolic function assessment
 Weight measurement
 Blood pressure measurement
 Assessment of clinical symptoms of congestion
 Assessment of clinical signs of congestion
 Assessment of activity level
 Patient education
 Beta-blocker therapy in patients with HF and LVSD
 ACEI or ARB in patients with HF and LVSD
 Warfarin therapy in patients with atrial fibrillation
ACC/AHA, American College of Cardiology/American Heart Association;
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.
Bonow RO, et al. J Amer Coll Cardiol. 2005;46:1144-1178.
42