Acute Decompensated Heart Failure in Hospitalized Patients

Michael M. Givertz, M.D.Medical Director, Heart Transplant/Mechanical Circulatory Support

Brigham and Women’s HospitalAssociate Professor of Medicine

Harvard Medical SchoolBoston, MA

The 1st Kuwait-North American Update in Internal Medicine

Heart Failure is a Progressive Disease

The Course of Heart Failure

Goodlin et al., J Am Coll Cardiol 2009;54:386

Trends in ADHF Morbidity/Mortality

Chen et al., JAMA 2011;306:1669

Markers of Advanced Disease and Poor Prognosis

• Severe (objective) exercise intolerance• ACE inhibitor or β-blocker intolerance• High-dose diuretics• RV failure, 2 pulmonary hypertension• Hyponatremia, anemia, hyperuricemia• Chronic kidney disease (CKD)• Cardiac cachexia

Muscle Wasting in Heart Failure

Repeat Hospitalizations and Death

Setoguchi et al., Am Heart J 2007;154:260

6-12 months

ADHF: Who are They?

• Older (mean age 70s)• ≈50% women• 40-50% preserved EF• Over 85% with chronic HF• Multiple co-morbidities

– Hypertension– Diabetes– Chronic kidney disease

Shortness of Breath is the Main Reason for HF Hospitalization

Congestion (Not Low Output) is the Main Finding in Hospitalized Patients

Systolic blood pressure (%)1

> 140 mm Hg 50 90 – 140 mm Hg 48 < 90 mm Hg 2Mean heart rate (bpm)2 ≈90PCWP (mm Hg)2 25 – 30Cardiac index2 Usually preserved

1Fonarow et al. Rev Cardiovasc Med 2003;4 Suppl 7:S212VMAC Investigators. JAMA 2002;287:1531

Congestion is Often Unrecognized and Precedes Hospitalization

Adamson et al., J Am Coll Cardiol 2003;41:565Yu et al., Circulation 2005;112:841

HR

PADP

PASP

CardioMEMS: Pressure Measurement System

Dear Michael M. Givertz, MDA new reading has come in for your patient, 31-003 C-Z which violated the alert threshold set up for "Mean Pressure above 20.0 mmHg". The reading was taken on 25 Jan 04:06 EST.

Systolic: 89Diastolic: 51Mean: 66Heart Rate: 91

Pressure waveform is attached.

Thank you,CardioMEMS Alert System

0 90 180 270 360 450 540 630 720 810 9000

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Treatment Control

6 Months 15 Months

CHAMPION Study: HF Hospitalizations

p < 0.001, based on Negative Binomial Regression

HF

Hos

pita

lizat

ions

, no.

At RiskTreatment 270 262 244 209 168 130 107 81 28 5 1Control 280 267 252 215 179 138 105 67 25 10 0

ACC/AHA Guidelines for ADHFGuidelines

N=25

Class IN=18

Class IIN=5

Class IIIN=2

IIaN=4

IIbN=1

Evidence AN=1

Evidence BN=3

Evidence BN=1

Evidence CN=3

Evidence CN=14

Evidence BN=2

Evidence CN=1

Consensus opinion 72%, “Evidence” 28%

Class I, Level of Evidence A

• Concentrations of BNP1 or NT-proBNP2 should be measured in patients being evaluated for dyspnea in which the contribution of HF is not known. Final diagnosis requires interpreting these results in the context of all available clinical data and ought not to be considered a stand alone test.

1Maisel et al., N Engl J Med 2002;347:161 (BNP Study)2Januzzi et al., Am J Cardiol 2005;95:948 (PRIDE Study)

Unfortunately, the routine use of serial natriuretic peptide measurements to monitor hemodynamics has not been shown to be helpful in improving the outcomes of the hospitalized patient with HF (ACC/AHA)

Diuretics for ADHF and Fluid Overload• Treatment with IV loop diuretics should begin

in the ED without delay, as early intervention may be associated with better outcomes (Level of evidence B).

• If patients are already receiving loop diuretics, initial IV dose should equal or exceed chronic oral dose (Level of evidence C).

• When a patient with congestion fails to respond to IV diuretics, consider increased dose of loop diuretic, addition of second diuretic, continuous infusion of loop diuretic (Level of evidence C)

DOSE Study

Felker et al., N Engl J Med 2011;364:797

DOSE Study

• 308 patients with ADHF• Randomized 2x2 to low vs. high-dose

furosemide and IV bolus vs. continuous infusion

• No differences at 72 hours in:– Global symptom assessment (1° efficacy endpoint)– Change in renal function (1° safety endpoint)

Felker et al., N Engl J Med 2011;364:797

Death, Rehospitalization, or ED Visit

Felker et al., N Engl J Med 2011;364:797

Secondary Endpoints: Low vs. High Dose Strategy

Low High P value

Dyspnea VAS AUC at 72 hours 4478 4668 0.041

% free from congestion at 72 hrs 11% 18% 0.091

Change in weight at 72 hrs -6.1 lbs -8.7 lbs 0.011

Net volume loss at 72 hrs 3575 mL 4899 mL 0.001

Change in NTproBNP at 72 hrs (pg/mL) -1194 -1882 0.06

% Treatment failure 37% 40% 0.56

% with Cr increase > 0.3 mg/dLwithin 72 hrs

14% 23% 0.041

Length of stay, days (median) 6 5 0.55

Cardiorenal Syndrome: Worsening Renal Function During Treatment of ADHF

• Increase in creatinine ≥ 0.3 mg/dl• Occurs in 15-30% of admissions• Risk factors:

– Older age– HTN, DM– Baseline renal dysfunction

• May be associated with adverse outcomes during the hospitalization and post-discharge

Gottlieb et al., J Card Fail 2002;8:136Forman et al., J Am Coll Cardiol 2004;43:61

Transient vs. Persistent Worsening Renal Function

Aronson et al., J Card Fail 2010;16:541

N = 467 with ADHF, WRF in 115 (24%)

+1.17

+0.60

Ultrafiltration: An Attractive Alternative to Diuretics

• More effective way to restore sodium balance1

– removal of isotonic vs. hypotonic saline• No effect on serum electrolytes• Rapid and predictable fluid removal• Does not stimulate neurohormones• May restore diuretic responsiveness and

improve long-term outcomes2

1Jessup and Costanzo, J Am Coll Cardiol 2009;53:5972Agostoni et al., J Am Coll Cardiol 1993;21:424

Minimally Invasive Ultrafiltration

• FDA approved, portable device• Non-ICU, routine nursing• PICC or central line• UNLOAD (sponsor-initiated)

– Greater weight loss at 48 hours compared to IV diuretics (5 vs. 3.1 kg; p < 0.001)

– Decreased HF hospitalization at 90 days

Costanzo et al., J Am Coll Cardiol 2007;49:675

CARRESS Study

Bart et al., N Engl J Med 2012;367:2296

N = 188 with ADHF, Cre ↑ ≥ 0.3, persistent congestionRandomized to UF vs. stepped pharmacologic care

CARRESS Study: Primary Endpoint

Bart et al., N Engl J Med 2012;367:2296

Cre ↑ 0.23

Cre ↓ 0.04

CARRESS: Adverse Events

Bart et al., N Engl J Med 2012;367:2296

• More patients in UF group (72%) had SAEs compared to stepped pharmacologic care (57%)– Renal failure– Bleeding– IV catheter-related

• No difference in 60-day mortality or rate of death or HF rehospitalization

Options for Diuretic Resistant Patients

• Vasodilators– IV Nitroprusside, nitroglycerin– Hydralazine/nitrates

• Positive inotropes– Dobutamine– Milrinone– Dopamine (renal-dose vs. higher doses)

• Mechanical circulatory support

Dobutamine: Interpatient Variability

Colucci et al., Circulation 1986;73:III175

Tolerance to (Not All) Inotropes

N = 20, severe chronic HF, CI 1.63 L/min/m2

Mager et al., Am Heart J 1991;121:1974

Is There Really a Role for Low-Dose Dopamine?

Chen et al., JAMA 2013:310:2533

N = 380 with ADHF and estimated GFR 15-60 ml/minRandomized to dopamine 2 mcg/kg/min vs. placebo

ROSE Study

No effect on symptoms, 60-day readmission or 180-day mortalityMore tachycardia

Chen et al., JAMA 2013:310:2533

Worst Prognosis with Inotrope Dependence

Hershberger, J Card Fail 2003;9:180 Rogers, J Am Coll Cardiol 2007;50:741

Community-based Clinical trial

ADHF is a Good Time to Address Risks and Co-Morbidities

• Arrhythmias or conduction disease– consider ICD for primary prevention– AF: consider amiodarone/CV, ablation– LBBB: consider CRT*

• Risk of thromboembolism: need for anticoagulation or anti-platelet therapy

• Anemia, diabetes, obesity, sleep apnea• Advanced directives

*should NOT be used as a “bail-out”

Dying with HF is Rarely Unexpected

• N = 160• Mean age 60, 74% male• Mean duration of HF: 5 years• 40% died in hospital, 10% with hospice• Within 6 months of death:

– 93% NYHA class III or IV– 74% hospitalized at least once– mean Na 128, Cre 3.1, Hct 30

Teuteberg et al, J Card Fail 2006;12:47

Comprehensive Discharge Instructions

Six key aspects of care• Diet• Medications (adherence and uptitration)• Activity level• Follow-up appointments• Daily weights• What to do if HF worsens?

Thank you for your attention