Hf nurse ccreview2011

Acute Heart Failure

Allen S. Anderson, M.D., FACC

Director, Heart Failure ProgramMedical Director of Cardiac TransplantationAssociate Professor of MedicineUniversity of Chicago Medical Center

Diagnosis and Treatment

TheTheCCenter forenter for

HHearteartFFailureailure

ManagementManagement

Diagnosis of CHF: Clinical Diagnosis of CHF: Clinical ChallengeChallenge

• Symptoms and signs of heart failure like shortness of breath and edema have a broad differential diagnosis

• Physical exam is neither sensitive nor specific for CHF and, even in good hands, there are often errors

• CXR findings have limited accuracy for CHF

• One-third to one-half of patients with CHF have normal systolic function

Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85

Goals for Therapy of Acute Goals for Therapy of Acute Decompensated Heart FailureDecompensated Heart Failure

Absence of orthopnea

No peripheral edema

No hepatomegaly/ascites

Valsalva square wave absent

Jugular venous pressure < 8 cm

Warm extremities

Systolic blood pressure > 80

SBP-DBP/SBP > 0.25

Pulmonary capillary wedge pressure < 15 mmHg

Right atrial pressure < 8 mmHg

Systemic vascular resistance < 1200 dynes-sec-cm-5

Systolic blood pressure > 80 mmHg

Assessed Clinically Measured Directly

Stevenson LW. Eur J Heart Failure 1999;1:251-257

The Physical ExamAs A Diagnostic Test

PCWP>20- 22 mmHg

Sensitivity Specificity Can’t tell

Orthopnea 90% 95%

JVP inc. 80% 98% 15%

Valsalva 90% 90% 25%

HJ Reflux 92% 81% ?

Perip edema 25% 95% 5%

Rales 15% 95%

From Ewy, McIntyre et al, Stevenson & Perloff, Zema et al.

Invasive Hemodynamic Assessment

• Invasive• Significant Complications• Expensive• Requires ICU or Cath Lab setting• Data sometimes difficult to interpret

Goals of Acute HF Therapy

• Alleviate symptoms• Treat volume overload• Preserve/improve end organ function• Limit hospitalization• Initiate/optimize chronic therapy• Prevent readmission• Improve long-term outcomes

Rapid Assessment of Hemodynamic StatusRapid Assessment of Hemodynamic Status

Congestion at Rest

LowPerfusion

at RestC

NO

NO YES

YES

L

A BWarm &

DryWarm &

Wet

Cold & WetCold & Dry

(Complex)(Low Profile)

Signs/Symptoms of Congestion:

Orthopnea / PNDJV DistensionHepatomegalyEdemaRales (rare in chronic

heart failure)Elevated est. PA

systolicValsalva square wave

Possible Evidence of Low Perfusion:Narrow pulse pressure Cool extremitiesSleepy / obtunded Hypotension with ACE inhibitorLow serum sodium Renal Dysfunction (one cause)

Current Treatment of Acute Heart FailureCurrent Treatment of Acute Heart Failure

DiureticsAquaretics

Ultrafiltration

Reducefluid

VolumeNa+

&H20

Vasodilators

DecreasePreload

AndAfterload

Inotropes

AugmentContract-

ility

Diuretic Resistance• Poor oral absorption due to gut edema• Decreased perfusion of kidney results in decreased delivery

of loop diuretics• Decreased GFR results in decreased filtered load of sodium• Volume depletion activates plasma renin activity and

stimulates SNS• Increased proximal tubule reabsorbtion of sodium,

particularly in setting of elevated AII and elevated catecholamine levels

• Increased distal reabsorbtion of sodium, stimulated by aldosterone

• Associated with tubular hypertrophy: resetting basal rates of sodium reabsorbtion.

Diuretic Principles

• The right dose is what it takes to effect diuresis– as high as it takes– as low as you can

• High dose loop vs loop+metolazone• Continuous IV infusion of loop diuretic• Flexible dosing• Daily weights

Change in Weight From Admission to Discharge

The ADHERE Registry First Quarter 2002 Benchmark Report. 2002:29

Primary End PointWeight Loss at 48 Hr

Primary End PointWeight Loss at 48 Hr

Freedom From Re-hospitalization for Heart

Failure

Therapy CO PCWP BP HRArrhythmia

Shorter Onset

LongerOffset

Dopamine (ng/kg/min)

Low (<3)Mod (3–7)High (7–15)

↔↑

↑↑

↔↔↔

↔↑

↑↑

↔↑

↑↑

↔↑↑

↑↑↑

+++++++++

000

Dobutamine ↑↑↑ ↓ ↔ ↑ ↑↑ +++ 0

Milrinone ↑↑ ↓ ↓ ↑ ↑↑ + ++

Nitroglycerin ↑ ↓↓ ↓↓ ↔ ↔ +++ 0

Nesiritide ↑ ↓↓ ↓ ↔ ↔ ++ ++

Nitroprusside ↑ ↓↓ ↓↓↓ ↔ ↔ ++++ 0

↑ increase; ↓ decrease; + effect (number of and qualitatively associated with degree of effect); 0 no effect

Intravenous Agents for Heart Failure

Reference: Adapted from Young JB. Rev Cardiovasc Med .2001;2(suppl 2):S19.

Most Common IV MedicationsAll Enrolled Discharges (n=105,388) October 2001-January 2004

0

10

20

30

40

50

60

70

80

90

100

Pat

ien

ts (

%)

IV Diuretic Dobutamine Dopamine Milrinone Nesiritide Nitroglycerin Nitroprusside

IV Vasoactive Meds

88%

6% 6% 10%3% 1%

10%

Profiles and Therapies of Profiles and Therapies of Advanced Heart FailureAdvanced Heart Failure

Yes

R. Bourge, UAB Cardiology (adapted from L. Stevenson)Stevenson LW. Eur J Heart Failure 1999;1:251-257

No

Warm and DryPCW and CI

normal

Warm and WetPCW elevated

CI normal

Cold and WetPCW elevatedCI decreased

Cold and DryPCW low/normal

CI decreased

VasodilatorsNitroprussideNitroglycerine

Nesiritide

Inotropic DrugsDobutamine

MilrinoneCalcium Sensitizers

Nl SVR High SVR

Congestion at Rest

LowPerfusion

at Rest

No

Yes

Limitations Of Traditional Vasodilators

• Tachyphylaxis• Headache • Underdosed• Titration required

NitroglycerinNitroglycerin

NitroprussideNitroprusside

• Difficult titration • ICU (± arterial line)• Coronary “steal”• Toxic metabolites• Increased renin

Reference: Fonarow GC. Rev Cardiovasc Med. 2002;3(suppl 4):S18

Nitroglycerin dose and change in PCWP during treatment with Nitroglycerin

0

20

40

60

80

100

120

140

160

180

0 3 6 9 12 15 18 21 24

Time (hours)

NT

G d

os

e (

mic

rog

ram

s/m

in)

-8

-7

-6

-5

-4

-3

-2

-1

0

Ch

an

ge

in P

CW

P (m

mH

g)

NTG Dose

Change in PCWP*

*

**

*

*

[n=9 (<3 hrs); n=12 (>3 hrs)]

U. Elkayam et al. Am J Card. 2004: 93; 237-240

* p<0.05 versus baseline

VMAC Trial: Hemodynamic Improvement

Nitroglycerin Nesiritide

Placebo

BL 1 2 3-10

-9

-8

-7

-6

-5

-4

-3

-2

-1

0

# p < 0.05 versus placebo* p < 0.05 versus NTG

# *

# * #

* #

#

# *

Time (hours)

Mean Change from Baseline (mm Hg)

(All Treated CatheterizedPatients, as Randomized)

References: 1. Publication Committee for the VMAC Investigators (Vasodilation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerinfor the treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002;287:1531-1540.2. NATRECOR® Full Prescribing Information.

Randomized (n=7141)

Study population-ASCEND

Placebo MITT=3511

Placebo (n=3577)• Did not receive study drug (n=66)

Hypotension (n=28)

Exclusion criteria (n=8)

Physician decision (n=6)

Participant withdrew consent (n=14)

Other reason (n=10)

Nesiritide MITT=3496

Nesiritide (n=3564)•Did not receive study drug (n=68)

Hypotension (n=26)

Exclusion criteria identified (n=9)

Physician decision (n=6)

Participant withdrew consent (n=16)

Other reason (n=11)

Co-Primary outcome: 30-day all-cause mortality or HF rehospitalization

10.1

4.0

6.1

Hazard Ratio 0.93 (95% CI: 0.8,1.08) P=0.31

9.4

3.6

6.0

Placebo

Nesiritide

HF Rehospitalization30-day Death/HF Rehospitalization

30-day Death0

2

4

6

8

10

12

Risk Diff (95 % CI) -0.7 (-2.1; 0.7) -0.4 (-1.3; 0.5) -0.1 (-1.2; 1.0)

%

All Subjects N=6836

SexFemaleMale

N=2335 N=4501

Age≤ 6465-74≥ 75

N=3029N=1774N=2033

Race

WhiteBlack or African AmericanAsianOther

N=3849N=1018N=1671N= 297

Region

North AmericaLatin AmericaAsia-PacificCentral EuropeWestern Europe

N=3098N= 644N=1668 N= 956N= 470-10 -5 0 5 10

30 day death/HF readmission subgroups

Difference (%) and 95% Confidence Interval

Risk Difference <1: Favors Nesiritide; Risk Difference >1: Favors Placebo

All Subjects N=6836

Baseline SBP (mmHg)< 123

≥ 123

N=3346

N=3490

Baseline Ejection Fraction (%)<40

≥ 40

N=4362

N=1187

Renal function- MDRD GFR (mL/min/m2)

<60

≥ 60

N=3395

N=3093

History of CADNo

Yes

N=3092

N=3742

History of Diabetes MellitusNo

Yes

N=3923

N=2913

-10 -5 0 5 10




-10 -5 0 5 10

All Subjects N=6836

Inotrope Use at Randomization

No

Yes

N=6556

N=280

Vasodilators

None

Any IV Vasodilators

No IV Nitroglycerin

IV Nitroglycerin

N=5889

N=942

N=5943

N=892

Diuretic Use from Hosp through Rand

No

Yes

N=691

N=6145

Study Drug BolusNo

Yes

N=2609

N=4227

Time from Hosp to Rand

<15.53

≥15.53

N=3426

N=3410




70

60

50

40

30

20

10

0

10

20

30

40%

Su

bje

cts

24 Hours

Markedly Better

Minimally Worse

Moderately Better

Moderately Worse

Minimally Better

Markedly Worse

No Change

Co-Primary Endpoint: 6 and 24 hour dyspnea

70

60

50

40

30

20

10

0

10

20

30

40

% S

ub

ject

s

50

60

6 Hours

3444Placebo

13.4

28.7

34.1

21.7

P=0.030*

3416Nesiritide

15.0

29.5

32.8

20.3 3398Placebo

27.5

38.6

22.1

9.5

3371Nesiritide

30.4

37.8

21.2

P=0.007*

8.6

42.1% 44.5%

66.1% 68.2%

All Subjects N=6860 N=6769

SexFemaleMale

N=2343 N=4517

N=2308 N=4461

Age≤64 Years65-74 Years≥75 Years

N=3064 N=1779 N=2017

N=3011 N=1761 N=1997

Race

WhiteBlackAsianOther

N=3815 N=1022 N=1722 N=300

N=3758 N=1009 N=1702 N=299

Region

North AmericaLatin AmericaAsia-PacificCentral EuropeWestern Europe

N=3074 N=636 N=1719 N=962 N=469

N=3026 N=639 N=1698 N=949 N=457

0 1 20 1 2

OR <1: Favors Placebo; OR >1: Favors Nesiritide;Odds Ratio of Markedly/Moderately vs. Other

24 hours6 hours

Dyspnea at 6 and 24 HoursOdds for Moderate-Marked Improvement


SBP<123≥123

N=3369N=3491

N=3314 N=3455

GFR<60≥60

N=3494N=3121

N=3349 N=3075

Ejection Fraction

<40≥40

N=4385N=1186

N=4335 N=1171

CADNoYes

N=3115N=3743

N=3082N=3685

DiabetesNoYes

N=3930N=2930

N=3887 N=2882

0 1 2 0 1 2

24 hours6 hours




InotropesNoYes

N=6574 N=286

N=6481 N=288

Vasodilators

NoneAny IV VasoNo IV NitroIV Nitro

N=5912 N=943 N=5965 N=894

N=5835 N=929 N=5886 N=882

DiureticsNoYes

N=691 N=6169

N=679 N=6090

Study Medication Bolus

NoYes

N=2612 N=4248

N=2564 N=4205

Time from Hosp to Rand

<15.53≥15.53

N=3428N=3432

N=3369N=3400

0 1 20 1 2

24 hours6 hours



Placebo(n=3511)

Nesiritide(n=3496)

Difference (95% CI)

P-value

Persistent or worsening HF or all-cause mortality through discharge

4.8%(165)

4.2% (147)

-0.5(-1.5 to 0.5)

0.30

Days alive and outside of hospital through Day 30

20.7 20.90.2

(-0.13 to 0.53)

0.16

CV death or CV rehosp through Day 30

11.8% (402)

10.9%(372)

-0.9(-2.4 to 0.6)

0.24

Secondary endpoints

3383Placebo

3364Nesiritide

24 Hours

Markedly Better

Minimally Worse

Moderately Better

Moderately Worse

Minimally Better

Markedly Worse

No Change

Wellbeing at 6 and 24 hours (markedly/moderate)

70

60

50

40

30

20

10

0

10

20

30

40

% S

ub

ject

s

50

60

3430Placebo

3406Nesiritide

6 Hours

70

60

50

40

30

20

10

0

10

20

30

40%

Su

bje

cts

50

60

P=0.318 P=0.018

12.2 13.2

28.1 28.2

34.6 33.9

22.9 22.0

24.9 27.1

38.8 38.6

23.6 22.6

9.8 9.2

Renal Safety

Anytime Through Day 30

Placebo(n=3509)

Nesiritide

(n=3498)

P-value

>25% decrease eGFR 29.5% 31.4% 0.11

End of Treatment Creatinine

Creatinine (mg/dL)

Cu

m D

ist

0 2 4 6 80

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Discharge or 10 day Creatinine

Creatinine (mg/dL)

Cu

m D

ist

0 2 4 6 80

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

NesiritidePlacebo

Placebo(n=3509)

Nesiritide(n=3498)

Risk Difference (95% CI)

P- value

Any hypotension (Through Day 10/discharge)

15.3%(538)

26.6% (930)

11.3(9.4 to 13.1)

<.001

Asymptomatic Hypotension

12.4%(436)

21.4%(748)

9.0(7.2 to 10.7)

<.001

Symptomatic Hypotension4.0%(141)

7.1%(250)

3.1(2.1 to 4.2)

<.001

Hypotension

COMBINED 30 day w/out ASCEND 1.28 (0.73, 2.25)

30-day mortality meta-analysis

1 100.1

Odds Ratio (95% CI)

PROACTION (N=237) 6.93 (0.89, 53.91)

Mills (N=163) 0.38 (0.05, 2.74)

Efficacy (N=127) 1.24 (0.23, 6.59)

Comparative (N=175) 1.43 (0.50, 4.09)

PRECEDENT (N=147) 0.59 (0.18, 2.01)

VMAC (N=498) 1.63 (0.77, 3.44)

ASCEND-HF (N=7007) 0.89 (0.69, 1.14)

COMBINED with ASCEND 1.00 (0.76, 1.30)

University of ChicagoUniversity of Chicago

Center for Heart Failure ManagementCardiac Transplant Service

Allen S. Anderson, M.D., FACC Director, Center for Heart FailureMedical Director Transplant Service

Valluvan Jeevanandam, M.D.Chief, Cardiothoracic SurgerySurgical Director Transplant Service

Transplant CoordinatorsCatherine Murks, RN, CNPRosalind Davis, RN

Heart Failure CoordinatorsElinor Lowry, RNBarbara Valentine-Bates, RN

Transplant Social WorkerRina Murao, LCSW

Education

Hf nurse ccreview2011