Acute(ly) Decompensated Heart Failure Brian C. Jensen, MD July 12, 2010.

Acute(ly) Decompensated Heart Failure

Brian C. Jensen, MDJuly 12, 2010

Objectives

Is this heart failure?

How sick is this patient?

What needs to be done now and what can wait until morning?

When do I need to involve my resident?

When do I need to involve the cardiology fellow?

Definition

Heart Failure a complex clinical

syndrome that results from the inability of the

heart to meet the metabolic

demands of the body

Heart Failure with Preserved Ejection Fraction?!?

Heart Failure with Preserved Ejection Fraction (HFpEF)Systolic Dysfunction

EF < 40%EF > 40 %

Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200

40%

60%

Heart Failure Statistics

AHA Statistical Update: Circulation. 2009;119:e21-e181

5.7 million people have HF

670,000 new cases in 2006

292,000 annual deaths due to HF

1.1 million hospitalizations per year

Largest Medicare expenditure

$37 billion in 2006

Epidemiology of HF

Gheorghiade M, et al. Circulation 2005;112:3958-68

ADHERE(n=110 000)

Euro-HF(n=11 000)

OPTIMIZE-HF(n=48 612)

Demographic characteristics

Mean age, y 75 71 73

Women (%) 52 47 52

Known heart failure (%) 75 65 87

Preserved EF (%) 40 54 49

Medical history (%)

CHD 57 68 50

Hypertension 72 53 71

Diabetes 44 27 42

Atrial fibrillation 31 43 31

Renal insufficiency 30 17 30

COPD 31 ... 28

Causes of Heart FailureCoronary Artery Disease: Dead Meat Don’t Beat

Causes of Heart FailureCardiomyopathy

Felker, GM et al. N Engl J Med 2000;342: 1077-84

NomenclatureStage vs. Class

ACC-AHA Stage NYHA Functional Class

I Asymptomatic

II Symptomatic with moderate exertion

III Symptomatic with minimal exertion

IV Symptomatic at rest

A At high risk for HF but without structural heart disease or symptoms of HF (e.g. patients with hypertension or CAD)

B Structural heart disease but without symptoms of HF

C Structural heart disease with prior or current symptoms of HF

D Refractory HF requiring specialized interventions

Adapted from: Farrell MH, Foody JM, Krumholz HM. JAMA 2002;287:890

Classification of Recommendations and Level of Evidence

Level A: Data derived from multiple randomized clinical trials or meta-analyses Multiple populations evaluated

Level B: Data derived from a single randomized trial or nonrandomized studies Limited populations evaluated

Level C: Only consensus of experts opinion, case studies, or standard of care

Very limited populations evaluated

Class I Benefit >>> Risk

Procedure/ Treatment SHOULD be performed/ administered

Class IIa Benefit >> RiskAdditional studies with focused objectives needed

IT IS REASONABLE to perform procedure/administer treatment

Class IIb Benefit ≥ RiskAdditional studies with broad objectives needed; Additional registry data would be helpful

Procedure/Treatment MAY BE CONSIDERED

Class III Risk ≥ BenefitNo additional studies needed

Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

Heart Failure is Progressive

Prognosis in Advanced Heart FailureUnchanged in 20 years

Stevenson LW, Rose EA. Circulation 2003;108:3059

Stage D, NYHA Class IV 50% Mortality

Acute cardiogenic shock ImminentEnd organ dysfunction 1 monthInotrope-dependent 3-6 monthsACE-inhibitor intolerant 6 monthsCachexia, hyponatremia, CKD 6-12 monthsTolerating oral therapies ± 12 monthsStabilized to NYHA Class III > 24 months

Heart Failure in ContextOne Year Mortality

0

10

20

30

40

50

60

70

80

90

AIDS Leukemia Lung Cancer Pancreatic Cancer End-stage HF with Optimal Medical

ManagementDiagnosis

1 Y

ear

Mo

rtal

ity

(%)

Rose EA, et al. N Engl J Med. 2001 Nov 15;345(20):1435-43.

It’s 2:30 a.m. You’re paged to the ED to see this guy…

EVALUATION

DiagnosisModified Framingham Clinical Criteria

MAJOR MINORParoxysmal Nocturnal Dsypnea (PND) Bilateral leg edema

Orthopnea Nocturnal cough

Elevated jugular venous pressure (JVD) Dyspnea on ordinary exertion

Pulmonary rales Hepatomegaly

Third heart sound (gallop) Pleural effusion

Cardiomegaly on chest x-ray Tachycardia > 120 bpm

Pulmonary edema on chest x-ray Weight loss > 4.5 kg in 5 days

Diuresis > 4.5 kg in 5 days

McKee PA et al N Engl J Med 1971; 85:1441

Diagnosis requires 2 major or 1 major and 2 minor criteria

“Left” and “Right” Heart Failure

Distended Jugular Veinselevated right atrial pressure

Hepatomegalyelevated IVC pressure

Peripheral Edemaelevated capillary bed pressure

Pulmonary rales (“crackles”)elevated capillary pressure

S3 or S4 gallopincreased LV pressure, decreased compliance

Orthopneaincreased venous return

Evaluation of Heart Failure

EKGQ waves, LVH, heart block, tachyarrhythmia

CXRpulmonary edema, other causes of dyspnea

Blood testsChemistry panel: renal function, sodium, glucoseLiver function testsTnIBNP

EchocardiogramFunction (systolic and diastolic) ?Structure (LVH, dilation, valves, shunts)

Cardiac catheterization? “Left heart cath” and/or right heart cath

Decompensated Heart FailureWhy?

It is recommended that the following common potential precipitating factors for acute HF be identified as recognition of these comorbidities is critical to guide therapy:

• acute coronary syndromes/coronary ischemia• severe hypertension• atrial and ventricular arrhythmias• infections• pulmonary emboli• renal failure• medical or dietary noncompliance

New

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII Precipitating Factors for Acute HF

Copyright restrictions may apply.

Predictors of In-Hospital Mortality

ADHERE. JAMA 2005; 293:572-80

BUN > 43

SBP < 115

Creatinine > 2.75

Acute Decompensated Heart FailureSigns and Symptoms

“WET”

Dyspnea, orthopnea, PND, morning cough, peripheral

edema, rales, ascites, hepatic congestion, jugular

venous distention

CARD

IAC

OU

TPU

T

PULMONARY CAPILLARY WEDGE PRESSURE

“COLD”

Nausea, early satiety, altered mental status, acidosis, worsening renal or hepatic function, reduced capillary refill,

cold skin, hypotension, narrow pulse pressure

Inpatient TriageDecompensated Heart Failure

WARM AND DRYCompensated

Optimize oral therapy

Outpatient

COLD AND DRYLow Flow State

Inotropes, vasodilators, ?IABP

ICU

COLD AND WETDecompensated

Diuretics, vasodilators, inotropes

ICU

WARM AND WETCongested

Diuretics

ED or Inpatient

Adapted from Nohria,J Cardiac Failure 2000;6:64

CARD

IAC

OU

TPU

T

PULMONARY CAPILLARY WEDGE PRESSURE

Who’s Cold?Proportional Pulse Pressure

Pulse PressureSystolic BP- Diastolic BP

Proportional Pulse PressurePulse Pressure

Systolic BP

Stevenson LW and Perloff JK. JAMA 1989;261(6):884-8

Proportional Pulse Pressure ≤ 25% predicts Cardiac Index ≤ 2.2Sensitivity 91%Specificity 83%

Who’s Wet?How well does physical exam predict PCWP > 22 mmHg?

Stevenson LW and Perloff JK. JAMA 1989;261(6):884-8

Finding Sensitivity SpecificityJVP > 11cm 67% 74%Edema > trace 48% 69%Increased apical P2 37% 75%Rales 15% 85%Hepatomegaly 15% 92%S3 gallop 63% 40%Valsalva square root sign 13% 96%

Measurement of BNP

Measurement of natriuretic peptides (B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proNBP) can be useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of HF is uncertain. Measurement of natriuretic peptides (BNP and NT-proBNP) can be helpful in risk stratification.

The value of serial measurements of BNP to guide therapy for patients with HF is not well established.

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

NO CHANGE

Modified

BNP is Increased with Heart FailureIrrespective of Ejection Fraction

Maisel AS, et al. JACC 2003;41:2010

BNP Levels Have Prognostic ValueDirect correlation with mortality and readmission rate

Logeart D, et al. JACC 20042;40:976-82

NT-pro BNPToo Scarred for Battle?

All Ages

Younger (< 75)

Older (> 75)

BNP guided“Intensive Care”

Usual Care

BATTLESCARRED: J Am Coll Cardiol, 2010; 55:53-60

Invasive Hemodynamic Monitoring (?)

Invasive hemodynamic monitoring can be useful for carefully selected patients with acute HF who have persistent symptoms despite empiric adjustment of standard therapies, and

a. whose fluid status, perfusion, or systemic orpulmonary vascular resistances are uncertain;b. whose systolic pressure remains low, or is associated with symptoms, despite initial therapy;c. whose renal function is worsening with therapy;d. who require parenteral vasoactive agents; ore. who may need consideration for advanced device therapy or transplantation.

New

I IIa IIb III

Invasive Hemodynamic Monitoring ESCAPE

ESCAPE: JAMA 2005;294:1625-1633

Shah MR et al, JAMA 2005;294(13):1664-1670

ESCAPEMETA-ANALYSIS

MANAGEMENT

Sodi

um E

xcre

tion

Rate

Maximal Response

Efficie

ncy

Threshold

Loop Diuretic Dose

How Much Diuretic Should I Give? …Enough

Ceiling Doses of Loop Diuretics

FUROSEMIDE BUMETANIDE TORSEMIDEIV po IV po IV po

Renal Insufficiency moderate 80 80 2-3 2-3 20-50 20-50

severe 200 240 8-10 8-10 50-100 50-100

Cirrhosis (normal GFR) 40 80-160 1 1 10-20 10-20

CHF (normal GFR) 40-80 160-240 2-3 2-3 20-50 20-50

Adapted from Brater C. New Engl J Med 1999

What to do when the creatinine risesHint: it’s always “pre-renal”

Check volume status Orthostatics, skin turgor, mucous membranes

Check blood pressure (especially at peak onset of vasodilators)

Restrict sodium intake (and water if hyponatremic)

Check for intrinsic renal problems U/A with sediment

Consider vasodilators or inotropes

Consider ultrafiltration

Intensifying the Diuretic RegimenChicken or egg?

New

When diuresis is inadequate to relieve congestion, as evidence by clinical evaluation, the diuretic regimen should be intensified using either:

a. higher doses of loop diuretics;b. addition of a second diuretic (such as metolazone,

spironolactone or intravenous chlorthiazide) orc. Continuous infusion of a loop diuretic.

DIG Trial Substudy (Chicken)

Ahmed A et al. Int J Cardiol 2007; 125(2):246-53

Prospective Observational Study (Egg)

Mielniczuk LM et al. J Card Fail 2008;14:388-93

Stable

Unstable

Vasodilator Therapy

In patients with evidence of severely symptomatic fluid overload in the absence of systemic hypotension, vasodilators such as intravenous nitroglycerin, nitroprusside or neseritide can be beneficial when added to diuretics and/or in those who do not respond to diuretics alone. New

I IIa IIb III

Vasodilator TherapyNipride: A Challenge

Mullens W et al. J Am Coll Cardiol 2008;52:200–7

MO

RTAL

ITY NIPRIDE

NO NIPRIDE

Retrospective anaylsis (n = 175)ADHF with Cardiac Index < 2.0

RR = 0.54

Vasodilator TherapyNesiritide: Good, Bad, or irrelevant?

BNP-CARDS: Witteles RM et al. JACC 50(19) 1835-40FUSION-II: Yancy CW et al. Circ: Heart Failure. 2008;1:9-16

RE

NA

L F

AIL

UR

E

EV

EN

T-F

RE

E

SU

RV

IVA

L

BNP-CARDS (RCT n=75)1. ADHF2. CRINesiritide vs. Placebo

FUSION-II (RCT n = 911)1. ACC/AHA Stage C/DOutpatient Nesiritide vs. Placebo

Kass DA. Nature Medicine 2009; (15): 24 – 25

InotropesDobutamine

Milrinone

Inotropes…are not “pressors”

Felker GM, O’Connor CM. Am Heart J 2001;142:393-401

DRUG SV HR SVR BPDobutamine +++ ++ +/- +/-

Milrinone +++ + (SVT) - -Dopamine* + ++ ++ ++

*assuming moderate dose (2 – 5 mcg/kg/min)

Infusion of Positive Inotropic DrugsOPTIME-CHF, etc. III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Routine intermittent infusions of vasoactive and positive inotropic agents are not recommended for patients with refractory end-stage HF.

Modified

Use of parenteral inotropes in normotensive patients with acute decompensated HF without evidence of decreased organ perfusion is not recommended.

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIII

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OPTIME-CHF: Cuffe, Califf, Adams KF et al. JAMA 2002; 287(12):1541

OPTIME-CHF (RCT n = 951)ADHF not requiring inotropeMilrinone (500 mcg/kg/min) vs. Placebo

Digoxin: the only “inotrope” with dataDIG Trial

N Engl J Med 1997;336:525-33

Total mortality

HF Mortalityp=NS

p=0.06

Digoxin: the only “inotrope” with dataDIG Trial

N Engl J Med 1997;336:525-33

RR 0.75p < 0.001D

eath

or H

F H

ospi

taliz

ation

Time (Months)

DIGOXIN

PLACEBO

Summary of HF Pharmacotherapy

SAVE LIVES IMPROVE SYMPTOMSACE inhibitors/ARBs Diuretics

Beta blockers DigoxinHydralazine/Nitrates Inotropes

Aldosterone inhibitors TNG, nipride, nesiritide

DISCHARGE

Reconciling and Adjusting MedicationsOPTIMIZE-HF and B-CONVINCED: Don’t Stop the b-Blockers

In patients with reduced ejection fraction experiencing a symptomatic exacerbation of HF requiring hospitalization during chronic maintenance treatment with oral therapies known to improve outcomes, particularly ACE inhibitors or ARBs and beta-blocker therapy, it is recommended that these therapies be continued in most patients in the absence of hemodynamic instability or contraindications.

New

OPTIMIZE-HF substudy: Fonarow GC et al. JACC 2008; 52(3) 190-199

WITHDRAWN

NOT TREATED

CONTINUED

NEWLY STARTED

MO

RTAL

ITY

DAYS SINCE DISCHARGEHR death = 2.3

OPTIMIZE-HF (n = 5791)1. Admitted with HF2. Pre-specified follow-upDeath or hospitalization

Can We Wait to Start the Beta-Blockers?IMPACT - HF

Galtis WA, et al. JACC 2004;43:1534

Free

dom

from

Dea

th a

nd R

ehos

pita

lizati

on

Days Since Randomization

Pre-discharge

Post-discharge

ACE-inhibitor or Beta-blocker First?CIBIS-III

Willenheimer R, et al. Circulation 2005;112:2426-2435

Bisoprolol first

Enalapril first

(HR 0.94 (077-1.16), p= 0.0.019 for non-inferiority

Even

t-fr

ee S

urvi

val

Time (months)

“Optimal Medical Management”The Neurohormonal Component

10 mg bid

50 mg tid

5 mg bid

20 mg qd

4 mg qd

20-40 mg bid

Enalapril (Vasotec)

Captopril (Capoten)

Ramipril (Altace)

Lisinopril (Prinivil, Zestril)

Trandolapril (Mavik)

Quinapril (Accupril)

Carvedilol (Coreg)

Metoprolol XL/CR (Toprol XL)

Bisoprolol (Zebeta)

25-50 mg bid

200 mg qd

10 mg qd

ACE-inhibitor

-Blocker

Seattle Heart Failure Modehttp://depts.washington.edu/shfm/app.phpl

Effective Outpatient CareBegins with an Inpatient

Post-discharge systems of care, if available, should be used to facilitate the transition to effective outpatient care for patients hospitalized with HF.

New


Euro Heart Failure Survey (n = 3261)Interview 12-weeks after discharge

Recall…

Implementation…

46%

67%

Core MeasuresUNCH

EF assessmentACEi/ARB (LVEF <40%)BB (LVEF <40%)Smoking cessationDischarge Instructions

o Activityo Dieto Follow Upo Medicationso Symptoms Worseningo Daily Weights and “Rule of 2’s”

Referral for Refractory End-Stage HFWe are here to help

Referral for cardiac transplantation in potentially eligible patients is recommended for patients with refractory end-stage HF. NO CHANGE

Referral of patients with refractory end-stage HF to an HF program with expertise in the management of refractory HF is useful. NO CHANGE


UNC Heart Failure TeamCardiology (919-843-5214)

Patty Chang, MD MHS Kirkwood Adams, MDCarla Sueta Dupree, MD PhDBrian Jensen, MD

Cardiothoracic Surgery (919-966-3381)Brett Sheridan, MDMichael Bowdish, MDMichael Mill, MD

Transplant CoordinatorsScott Kowalczyk, RN BSN CTCCKatie McMahon, RN BSN

VAD CoordinatorMandy Bowen, RN BSN

DiagnosisEchocardiogram

Normal Dilated Cardiomyopathy

The Hemodynamic or “Mechanical” ParadigmThe Cardiovascular system as “Pump and Pipes”

=1

4

6

https://www.clevelandclinic.org/heartcenter/images/guide/heartworks/heart_bloodvessels.jpg

The Hemodynamic or “Mechanical” ParadigmHeart Failure Defined by Weights and Measures

Neurohormonal ParadigmThe Starting Lineup

Renin

Angiotensin I

Aldosterone

Norepinephrine

Other players: Endothelin, Vasopressin, ANP, BNP, etc

chronotropy, inotropy, vasoconstriction, renin secretion

sodium retention, cardiac fibrosis

Angiotensin II

ACEvasoconstriction, cardiomyocyte hypertrophy, aldosterone and vasopressin release, thirst

Converts angiotensinogen to angiotensin I

Neurohormonal ParadigmIn Context

http://www.cvphysiology.com/Blood%20Pressure/BP015.htm

Norepinephrine

Eje

ctio

n F

ract

ion 60 %

20 %Time (yrs)

Compensatory Mechanisms

SecondaryDamage

Asymptomatic Symptomatic

Index Event

Mann, Circulation 1999; 100: 999-1008

Sympathetic Activation in Heart Failure“Fight or Flight” in the brain, heart and kidneys

Disease progression

Cardiac sympatheticactivity

-adrenergicreceptors

VasoconstrictionSodium retention

Myocardial toxicityIncreased arrhythmias

Renal and vascularsympathetic activity

Activationof RAS

b-AR

Adapted from Packer M. Progr Cardiovasc Dis. 1998;39(Supp I):39-52

a1-AR

CNS sympathetic outflow

b-Blockers

Decrease Salt and Water Intake

Renin-Angiotensin SystemFriend and Foe

http://en.wikipedia.org/wiki/File:Renin-angiotensin-aldosterone_system.png

ACE inhibitorsARBs

Aldosterone antagonists

Neurohormonal AntagonistsWhy we do what we do

Adapted from: Remme WJ et al. Eur. Heart J. 2001;22:1527-1560.

Events prevented per 1000 patient-hours of treatment

Therapy Hospitalizations Prevented Deaths prevented Evidence

ACE-inhibitor 99 13 SOLVD

Beta-blocker 65 38 MERIT-HF

Spironolactone 138 57 RALES

Digoxin 40 0 DIG

Neurohormonal BlockadeThe Foundation

Angiotensin-converting enzyme (ACE) inhibitors are recommended for all patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated . NO CHANGE

Use of 1 of the 3 beta blockers proven to reduce mortality (i.e., bisoprolol, carvedilol, and sustained release metoprolol succinate) is recommended for all stable patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. Modified



Hydralazine and NitratesA-HeFT

The combination of hydralazine and nitrates is recommended to improve outcomes for patients self-described as African-Americans, with moderate-severe symptoms on optimal therapy with ACE inhibitors, beta blockers, and diuretics.

New


Bidil

Placebo

Aldosterone antagonistsBenefits and risks

Addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine 2.5 mg/dL or less in men or 2.0 mg/dL or less in women and potassium should be less than 5.0 mEq/L. Under circumstances where monitoring for hyperkalemia or renal dysfunction is not anticipated to be feasible, the risks may outweigh the benefits of aldosterone antagonists.

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIRA

LES

Clas

s (II

I-)IV

RALES: Pitt B, et al. N Engl J Med 1999; 341(10):709-17

EPHESUSHF post MI

EPHESUS: Pitt B, et al. N Engl J Med 2003; 348(14):1309-21

RR death = 0.85RR death = 0.70

NO CHANGE

ACE-inhibitor or Beta-blocker First?CIBIS-III

(Willenheimer R, et al. Circulation 2005;112:2426-2435)

The GuidelinesOutpatient Management

Jessup M, Brozena S. NEJM 2003;348:2007

Ventricular Assist Devices

Consideration of an left ventricular assist device as permanent or “destination” therapy is reasonable in highly selected patients with refractory end-stage HF and an estimated 1-year mortality over 50% with medical therapy.


NO CHANGE

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Acute(ly) Decompensated Heart Failure Brian C. Jensen, MD July 12, 2010.

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Transcript of Acute(ly) Decompensated Heart Failure Brian C. Jensen, MD July 12, 2010.