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 (

%)

16

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)

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

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)

20

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)

21

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

26

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

27

Congestion May Contribute to the Progression of Heart

Failure in Patients Admitted With HF

28

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

29

*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

30

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

31

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

34

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

42