pulmonary congestion
TRANSCRIPT
Acute Heart FailurePulmonary Congestion
Mihai Gheorghiade MD, FACCProfessor of Medicine and Surgery
Director of Experimental TherapeuticsCenter for Cardiovascular Innovation
Northwestern University Feinberg School of Medicine, Chicago, Illinois
Conflict of Interest Conflict 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.
AHFSEpidemiology
• 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
Worsening Chronic Heart Failure: The Major Reason for HF
HospitalizationsWorsening chronic
heart failure (75%)
De novo heart
failure (23%)
Advanced/ end-stage
heart failure (2%)
Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21Cleland JG et al. Eur Heart J. 2003; 24: 442
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
ADHERE EURO HF OPTIMIZE-HF(107,920 pts.) (11,327 pts.) (48,612 pts.)
Any dyspnea (%) 89 70 90?
Dyspnea at rest (%) 34 40 45Fatigue (%) 32 35 23Rales (%) 68 N/A 65Peripheral edema (%) 66 23 65Systolic 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
Definition
• Hemodynamic congestion: high LV filling pressures.
• Clinical congestion: symptoms (dyspnea) and signs (JVD, rales, edema).
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
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
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
Cha
nge
(%)
-10
0
10
20
30
40
RV Systolic Pressure
Estimated PA Diastolic Pressure
Heart Rate
More than 50% of Patients Have Little or no Weight Loss During Hospitalization
Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21
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
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
Sur
viva
l (%
)
p < 0.001
No congestion (N=80)
1-2 congestion (N=40)
3-5 congestion (N=26)
Reassess at 4-6 weeks
• Sodium restriction• Fluid restriction• Loop diuretics• Thiazide diuretics• MR antagonists• Metolazone• Vasopressin Antagonists• Ultrafiltration/dialysis
Interventions to Relieve Congestion
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
*
Secondary Endpoints: Day 1Secondary Endpoints: Day 1
– 1.7 ± 1.8
– 1.0 ± 1.8
– 1.8 ± 2.0
– 0.9 ± 1.9
Both trialsP<0.001
Difference 0.7 kg 0.9 kg
Δ inDyspnea
(% of pts with baseline dyspnea)
Trial A Trial B
Δ in BW (kg)
Tolvaptan Placebo Tolvaptan Placebo
Both trialsP<0.001
37 35 33 31
24 24 2523
1611 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
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/m2
2.6 L/min/m2
19%
Rest Peak Exercise LVEFN=16*Baseline values are for the combined group†
P<.05 as compared with baseline
†
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Patients Admitted for Heart FailureIV Digoxin, 0.5 mg x 2
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
• 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 and outcomes.
Congestion in Heart Failure: Conclusions