congestion in heart failure mihai gheorghiade, md professor of medicine northwestern university...
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Congestion in Heart Failure
Mihai Gheorghiade, MD
Professor of Medicine Northwestern University
Feinberg School of MedicineChicago, 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
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.
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)
5
• Radiographic congestion and CTR often does not correlate with PCWP
Kono T, et al. Jpn Circ J. 1992;56:359-365.
Both Patients Have High PCWP
PCWP, pulmonary capillary wedge pressure; CTR, cardiothoracic ratio.6
Increase PA pressure
Systemic congestion
(JVD, edema)
RV + RA pressure
SYMPTOMS
Symptoms and Signs: The Tip of the Congestion Iceberg in HF
Abnormal LV function (systolic and/or diastolic)
LA and LV diastolic pressure
LVDP + impaired volume regulation
Dyspnea
Increased PCWP (congestion) Redistribution in pulmonary vascular bed
+ interstitial edema
Alveolar edema
Hydrostatic pressure Oncotic pressure Permeability Lymphatic drainage capacityAlveolar-capillary membrane integrity
Mitralregurgitation
Abnormal lung functionRespiratory muscle dysfunctionOther factors
RV, right ventricular; RA, right atrial; PA, pulmonary artery; LA, left atrial; LVDP, left ventricular diastolic pressure. 7
• Ability to predict PCWP >18-20 mm Hg in patients with severe heart failure
Sens. Spec. PPV NPV
Dyspnea on exertion 66 52 45 27Orthopnea 66 47 61 37Edema 46 73 79 46JVD 70 79 85 62S3 73 42 66 44CXR Cardiomegaly 97 10 61 --- Redistribution 60 68 75 52 Interstitial edema 60 73 78 53 Pleural effusion 43 79 76 47
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.
Absence of Specific Signs, Symptoms and CXR Findings Doesn’t Exclude High PCWP
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
Gheorghiade M, et al. Circulation. 2005;112:3958-3968.
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
11
Gheorghiade M, et al. Circulation. 2005;112:3958-3968.
AHFS: Hospitalizations
Worsening chronic HF (80%)
Acute de novo heart failure (diagnosed for the first time) (15%)
Advanced/end-stage/refractory HF (5%)
12
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.
Clinical Presentation of Patients Hospitalized with Heart Failure
(200,000 patients)
13
SBP >140 mm Hg1 50%SBP 90-140 mm Hg1 48%SBP <90 mm Hg1 2%
Mean heart rate (bpm)2 90
PCWP (mm Hg)2 25-30
Cardiac index2 usually preserved
Congestion, Not Low Cardiac Output: Main Finding in Hospitalized Patients
1 Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.2 The VMAC Investigators. JAMA. 2002;287:1531-1540. 14
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.
Outcomes
ADHERE EURO HF OPTIMIZE-HF
(150,000 pts) (11,327 pts) (50,000 pts)
> 2.5 kg weight loss (%) 50 N/A 50
HF Symptoms
Unchanged/worse < 1 < 3 Better (symptomatic) 40 40 Better (asymptomatic) 50 51
Length of stay (days) 4.3 (3, 7) 11 4 (3, 7)In-hospital mortality (%) 4 7 4Mortality at 2-3 mos (%) N/A 6.5 9Readmissions at 2-3 mos (%) N/A 24 31
15
Fonarow GC. Rev Cardiovasc Med. 2003;4(Suppl 7):S21-S30.
More Than 50% of Patients Have Little or No Weight Loss During Hospitalization
2%3%
15%
33%
24%
13%
6%7%
0
5
10
15
20
25
30
35
(<-20) (-20 to -15)(-15 to -10) (-10 to -5) (-5 to 0) (0 to 5) (5 to 10) (>10)
Change in Weight (lbs)
Pat
ien
ts (
%)
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Admission Discharge
Symptoms (%)
Dyspnea on exertion 79 58Dyspnea at rest 42 5Orthopnea 50 12
PND 33 4Fatigue 53 57
Signs (%)
JVP > 6 cm 33 6Rales 57 13S3 gallop 20 6Edema >2+ 50 13
PND, paroxysmal nocturnal dyspnea.Gattis WA, et al. J Am Coll Cardiol. 2004;43:1534-1541.
Change in Heart Failure Signs and Symptoms (Admission to Discharge)
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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)
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Congestion and Prognosis in Heart Failure
19
JVD & S3* Predict Hospitalization/Death
*Difficult to assess clinically.Drazner MH, et al. N Engl J Med. 2001;345:574-581.
Eve
nt-f
ree
surv
ival
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0 250 500 750 1000 1250 1500
Days
No S3
S3P<0.001
Eve
nt-f
ree
surv
ival
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
00 250 500 750 1000 1250 1500
Days
No JVP
JVPP<0.001
Endpoint 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)
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High PCWP at Hospital Discharge Is Associated with Higher Long-Term Mortality
Fonarow GC, et al. Circulation. 1994;90:I-488.
Time (months)
N=199
N=257
PCWP >16 mmHg
PCWP ≤16 mmHg
Mortality (%)
0 6 12 18 240
10
20
30
40
50
60
P=0.001
CI >2.6 L/min/m2
CI ≤2.6 L/min/m2
Mortality (%)
0 6 12 18 240
10
20
30
40
50
60
P=NS
N=236
N=220
Time (months)
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Post-discharge Freedom from Congestion Is Associated with Better Prognosis
Lucas C, et al. Am Heart J. 2000;140:840-847.
Criteria for congestion: Orthopnea, JVD, weight gain ≥2 lb in a week, need (0-5) to increase diuretic dose, leg edema
100
80
60
40
20
0 0 6 12 18 24
Months after reassess
Su
rviv
al (
%)
P<0.001
No congestion (N=80)
1-2 congestion (N=40)
3-5 congestion (N=26)
Reassess at 4-6 weeks
22
ESCAPE Investigators. Presented at the 77 th American Heart Association Scientific Sessions. Late Breaking Clinical Trials Session. New Orleans, LA. 11/10/2004.
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
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
Decreased cardiacperformance
Decreased cardiac output
Impaired renalfunction Decreased renal
perfusion
Increased water& Na+ retention(Congestion)
Diminishedblood flow
Neurohormonalactivation
Increased venous pressure
Modified from Abraham WT.
The Cardiorenal Syndrome in Heart Failure
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P<.05
P<.05
Raised venous pressure: A direct cause of renal sodium retention
0.5
0.8
1.1
1.4
0 2 4 6 8 0 6.25 12 18.75 25 0
Central Venous Pressure
GF
R (
ml/m
in)
mm Hg
High CVP significantlyimpairs GFR
GFR, glomerular filtration rate; BP, blood pressure.Firth JD et al. Lancet. 1988;1(8593):1033-1035.
Effect of Increasing Central Venous Pressure (CVP) on GFR in
Intact Dogs with Constant BP
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Congestion May Contribute to the Progression of Heart
Failure in Patients Admitted With HF
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Cohn J. N Engl J Med. 1996;335:490-498.
PathologicRemodeling
Low ejectionfraction
Death
Symptoms:DyspneaFatigueEdema
Chronicheartfailure
• Neurohormonal stimulation
• Endothelialdysfunction
• Vasoconstriction• Renal sodium
retention
Arrhythmia
Pump failure
Coronary artery disease
Hypertension
Cardiomyopathy
Valvular disease
Left ventricularinjury
Progression of Heart Failure
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*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.
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
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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.
Myocardial Injury in AHFS
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TnT, troponin T; TnI, troponin I.
Gheorghiade M, et al. Am J Cardiol. 2005;96(6A).
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
32
Perna ER, et al. Am Heart J. 2002;143:814-820.
1
Months
TnT >0.1 ng/mL (N=32)
TnT <0.1 ng/mL (N=46)
0 3 6 9 12 15 18 21 24 27 30 33 36
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
Su
rviv
al
AHFS: Prognostic Value of Tn T
33
Time
Car
dia
c F
un
ctio
n
Acute event
With each event, myocardial injury may contribute to progressive LV dysfunction
Gheorghiade M, et al. Am J Cardiol. 2005;96(6A-11A).
Death
Acute Exacerbations May Contribute to the Progression of Heart Failure
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ESCAPE
Results Study population had severe illness (mean
LVEF 20% and mean SBP 105.6 mm Hg) Trial discontinued early by DSMB due to lack
of efficacy No difference between groups in primary
endpoint of days neither dead nor hospitalized through 6 months (HR 1.00; 95% CI 0.83-1.21
Also no difference in frequency of rehospitalization or death (Figure)
Both groups had improvements in exercise and quality of life endpoints, with non-significant trend for larger improvement in PAC group
Conclusions Among patients hospitalized with recurrent
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 dead nor hospitalized compared with clinical assessment alone
Data cannot be extrapolated to patients that do have indication for PAC guided therapy
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.
SBP, systolic blood pressure.Presented at AHA Scientific Sessions 2004.www.cardiosource.com
Death by 6 months
P=NS
Rehospitalization by 6 months
P=NS25
20
15
10
5
0
%
PAC
1
0Control
2
3
35
%
NA:
CI
PCWP
RAP
1.8 2.3
27 19
15 9
1.9 1.2
22 18
12 8
2.1 2.1
25 15
12 8
1.9 2.1
22 17
9 8
CI, cardiac index; RAP, right atrial pressure.
Gheorghiade M, et al. Presented at ACC, 2005.
mEq/dL
Mortality at 6 Months in Patients Admitted with HF in the ESCAPE Trial
0
5
10
15
20
25
30
35
121-134 135-136 137-139 140-147
Mortality
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
Adamson PB, et al. J Am Coll Cardiol. 2003;41:565-571.
Pressure Change Hospitalization
Days Relative to the Event
Baseline -7 -6 -5 -4 -3 -2 -1 Recovery
Per
cen
t C
han
ge
-10
0
10
20
30
40RV Systolic Pressure
Estimated PA Diastolic Pressure
Heart Rate
Hospitalizations for Heart Failure:Congestion Precedes Hospitalization
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
*The most important predictor of prognosis.Gheorghiade M, et al. Circulation. 2005;112:3958-3968.
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
41
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.
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
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