Pulmonary congestion

1. Acute Heart Failure
Pulmonary Congestion
Mihai Gheorghiade MD, FACC
Professor of Medicine and Surgery
Director of Experimental Therapeutics
Center for Cardiovascular Innovation
Northwestern University Feinberg School of Medicine, Chicago, Illinois

2. Conflict of InterestConflict of Interest
Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma AG,
Cardiorentis Ltd, CorThera, Cytokinetics, CytoPherx, Inc, DebioPharm S.A.,
Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, INC,
Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Ono
Parmaceuticals USA, Otsuka Pharmaceuticals, Palatin Technologies, Pericor
Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay
Pharmaceuticals, Sticares InterACT,Takeda Pharmaceuticals North America,
Inc and Trevena Therapeutics; and has received signficant (> $10,000)
support from Bayer Schering Pharma AG, DebioPharm S.A.,
Medtronic,Novartis Pharma AG, Otsuka Pharmaceuticals, Sigma Tau, Solvay
Pharmaceuticals, Sticares InterACT and Takeda Pharmaceuticals North
America, Inc.

3. AHFS
Epidemiology
• 1 million admissions per year with the
primary diagnosis of HF in USA
• 3,000,000 admissions per year with primary
or secondary diagnosis of HF
• Post discharge event rate (readmissions/
death): 35%* at 60 days
.
*50% in pts. with BP<120mmHg at admission

4. Worsening Chronic Heart Failure:
The Major Reason for HF
Hospitalizations
Worsening chronic
heart failure (75%)
De novo heart
failure (23%)
Advanced/ end-stage
heart failure (2%)
Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21
Cleland JG et al. Eur Heart J. 2003; 24: 442

5. Demographic and Clinical
Characteristics of AHFS Patients
Median age (years) 75 Hx of Atrial Fibrillation 30%
Women >50% Renal abnormalities 30%
Hx of CAD 60% SBP >140 mm Hg 50%
Hx of Hypertension 70% SBP 90-140 mm Hg 45%
Hx of Diabetes 40% SBP <90 mm Hg 5%
Preserved EF 50%
Adams KF, et al. Am Heart J. 2005;149: 209.
Cleland JGF et al. Eur Heart J. 2003; 24: 442;
Fonarow GC, et al. J Am Coll Cardiol. 2007
Data on approximately 200,000 patients

7. ADHERE EURO HF OPTIMIZE-HF
(107,920 pts.) (11,327 pts.) (48,612 pts.)
Any dyspnea (%) 89 70 90?
Dyspnea at rest (%) 34 40 45
Fatigue (%) 32 35 23
Rales (%) 68 N/A 65
Peripheral edema (%) 66 23 65
Systolic BP (%)
< 90 mmHg 2 < 1 < 8
90 - 140 mmHg 48 70 44
> 140 mmHg 50 29 48
Adams KF et al. Am Heart J. 2005; 149: 209; Cleland JGF et al. Eur Heart J. 2003; 24: 442; Fonarow GC et al. J Am Coll Cardiol. 2005; 45: 345A
Hospitalizations for HF: Patient
Characteristics

8. Definition
• Hemodynamic congestion: high LV filling
pressures.
• Clinical congestion: symptoms (dyspnea)
and signs (JVD, rales, edema).

9. Congestion in Heart Failure* –
Potential deleterious effects
• LV Remodeling:
- increased afterload (wall stress)
- worsening mitral regurgitation
• Increased PA/RA pressure with systemic congestion
• Neurohormonal activation
• Subendocardial ischemia/cell death by
necrosis/apoptosis1
• Changes in extra cellular matrix structure and function1
• Progression of LV dysfunction
• Impaired cardiac drainage from coronary veins (diastolic
dysfunction)
• Lower threshold for arrhythmias
* The number of patients with congestion will probably increase due to a decrease in the rate
of sudden death (beta blockers, ICD)
1
Filippatos GS et al. Am J Physiol. 1999; 277: H445

10. Hemodynamic deterioration
(e.g., fluid overload)

Myocardial injury (Tn release)

Progression of heart failure
Congestion may Contribute to
Myocardial Injury
Gheorghiade et al. Am Heart J. 2003; 145: S3

11. Adamson PB et al. J Am Coll Cardiol. 2003; 41: 565
Congestion Precedes
Hospitalization
Pressure Change Hospitalization
Days Relative to the Event
Baseline -7 -6 -5 -4 -3 -2 -1 Recovery
Change(%)
-10
0
10
20
30
40
RV Systolic Pressure
Estimated PA Diastolic
Pressure
Heart Rate

12. More than 50% of Patients Have Little or no Weight
Loss During Hospitalization
Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21

13. Change in Heart Failure Signs and Symptoms
(Admission to Discharge)
Admission Discharge
Symptoms (%)
Dyspnea on exertion 79 58
Dyspnea at rest 42 5
Orthopnea 50 12
PND 33 4
Fatigue 53 57
Signs (%)
JVP > 6cm 33 6
Rales 57 13
S3 gallop 20 6
Edema > 2+ 50 13
Gattis WA et al. J Am Coll Cardiol. 2004; 43: 1534

14. Lucas C et al. Am Heart J. 2000; 140: 840
Post-discharge Freedom of Congestion is Associated with
Better Prognosis
Criteria for congestion: Orthopnea, JVD, wt. 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
Survival(%)
p < 0.001
No congestion (N=80)
1-2 congestion (N=40)
3-5 congestion (N=26)
Reassess at 4-6 weeks

18. • Sodium restriction
• Fluid restriction
• Loop diuretics
• Thiazide diuretics
• MR antagonists
• Metolazone
• Vasopressin Antagonists
• Ultrafiltration/dialysis
Interventions to Relieve Congestion

19. Diuretics
• Loop diuretics in pts. with CrCl < 30
• Have to be given bid to avoid rebound Na
reabsorbtion
• May use thiazides if CrCl > 30
• Use combination (e.g. furosemide +
thiazide), iv bolus or iv drips
• Metolazone in refractory HF or in pts. with
renal failure. Should not be used daily.
• Add spironolactone if Cr < 2.5 and K < 5.5

22. *
Secondary Endpoints: Day 1Secondary Endpoints: Day 1
– 1.7
± 1.8
– 1.0
± 1.8
– 1.8
± 2.0
– 0.9
± 1.9
Both trials
P<0.001
Difference 0.7 kg 0.9 kg
Δ in
Dyspnea
(% of pts with baseline
dyspnea)
Trial A Trial B
Δ in BW (kg)
Tolvaptan Placebo Tolvaptan Placebo
Both trials
P<0.001
37 35 33 31
24
24
25
23
16
11 14
11
–2 –3 –2 –3
–20
0
20
40
60
80
Tolvaptan Placebo Tolvaptan Placebo
(n=894) (n=915) (n=941) (n=914)
Improved
worsened
Markedly better
Moderately better
Minimally better
Worse

28. Acute Hemodynamic Effects of Digoxin in
Pts. with Systolic Dysfunction and Sinus
Rhythm
Gheorghiade M, et al. J Am Coll Cardiol. 1989;13:134.
PCWP Cardiac Index LVEF
N/AN/A
Baseline*: 32 mm Hg 40 mm Hg
Baseline*: 1.9 L/min/m
2
2.6 L/min/m
2
19%
Rest Peak Exercise LVEFN=16
*Baseline values are for the combined group†
P<.05 as compared with baseline
†
†
†
†
†
†
†
†
†
†
†
Patients Admitted for Heart Failure
IV Digoxin, 0.5 mg x 2

31. Management of Congestion in
Patients Hospitalized for HF
• Short term management of severe congestion
should include:
– Loop diuretics
– MR antagonists
– Tolvaptan (particularly in patients with low serum
sodium)
– Digoxin

32. • Congestion is an important predictor of mortality
and morbidity.
• Congestion is the primary cause of heart failure
hospital admissions and predicts readmissions.
• Hemodynamic congestion is often difficult to
recognize, delaying appropriate interventions.
• Clinical congestion often lags behind
hemodynamic congestion.
• Hemodynamic congestion contributes to
progression of heart failure.
• Improved methods to monitoring hemodynamic
congestion may improve clinical management
Congestion in Heart Failure:
Conclusions