Acute Heart Failure Management between Current Guidelines and Patient Needs

Susanna Sciomer - Francesco Fedele

IX International SymposiumHEART FAILURE & Co.IX International SymposiumHEART FAILURE & Co.

Milano, 18 Aprile 2009Milano, 18 Aprile 2009

“Re-thinking acute heart failure approach”“Re-thinking acute heart failure approach”

Dept. of Cardiovascular, Respiratory and Morphological Sciences

“Sapienza” University of Rome, Italy

Dept. of Cardiovascular, Respiratory and Morphological Sciences

“Sapienza” University of Rome, Italy

ESC guidelines 2005

++

Acute heart failure: a rapid onset or change in the signs and symptoms of HF, resulting in the need for urgent therapy. AHF may be either new HF or worsening of pre-existing chronic HF. Multiple cardiovascular and non-cardiovascular

morbidities may precipitate AHF.

Acute heart failure: a rapid onset or change in the signs and symptoms of HF, resulting in the need for urgent therapy. AHF may be either new HF or worsening of pre-existing chronic HF. Multiple cardiovascular and non-cardiovascular

morbidities may precipitate AHF.

STROKE VOLUME?STROKE VOLUME?

General clinical classificationGeneral clinical classificationGheorghiade M, Pang PS. JACC 2009; 53:557Gheorghiade M, Pang PS. JACC 2009; 53:557

Time

Func

tiona

l abi

lity

AHF

With each event, myocardial injury may contribute to progressive LV dysfunction

Acute Exacerbations Contribute to the Progression of the Disease

Gheorghiade M et al. Am J Cardiol. 2005; 96 (6A)

CHF

AHF

CHF

High post-discharge eventHigh post-discharge event

Worsening signs and symptoms, Neurohormonal and renal abnormalities Occurr soon after discharge

Worsening signs and symptoms, Neurohormonal and renal abnormalities Occurr soon after discharge

ESC guidelines 2008

GUIDELINESGUIDELINES

AHF between Current Guidelines and Patient Needs…

HF (as a diagnosis at hospital discharge) has tripled over the last 3

decades.This trend will likely

continue due to:aging population, improved

survival after myocardial infarction, better prevention of

sudden cardiac death.

HF (as a diagnosis at hospital discharge) has tripled over the last 3

decades.This trend will likely

continue due to:aging population, improved

survival after myocardial infarction, better prevention of

sudden cardiac death.

Currently available assessment modalities

combined with recent

advances in cardiovascular

therapies provide present-day

opportunities to improve post-

discharge outcomes.

Currently available assessment modalities

combined with recent

advances in cardiovascular

therapies provide present-day

opportunities to improve post-

discharge outcomes.

Management of AHF and diagnostic problems Management of AHF and diagnostic problems

Gheorghiade M, Pang PS. JACC 2009; 53:557Gheorghiade M, Pang PS. JACC 2009; 53:557

Diagnosis is more likely in the presence of multiple typical symptoms and Diagnosis is more likely in the presence of multiple typical symptoms and signs (ex. dyspnoea, fatigue, third heart sound, oedema, raised jugular signs (ex. dyspnoea, fatigue, third heart sound, oedema, raised jugular venous pressure.....)venous pressure.....)

The presence of several signs has a good specificity but a low sensibility The presence of several signs has a good specificity but a low sensibility

Need of instrumental objective data to assess the diagnosisNeed of instrumental objective data to assess the diagnosisNeed to exclude other pathologiesNeed to exclude other pathologies

True typical symptoms?True typical symptoms?

Evidence for Congestion(elevated filling pressures)

OrthopneaHigh Jugular Venous PressureIncreasing S3Loud P2EdemaAscitesRales (uncommon)Abdominojugular Reflux

Evidence for Low Perfusion

Narrow Pulse PressurePulsus AlterationsMay be Sleepy, ObtundedACE-inhibitor-Related Symptomatic HypotensionDeclining Serum Sodium LevelWorsening Renal Function

Congestion at Rest?

Low

Per

fusi

on a

t R

est? No

No

Yes

Yes

Warm and Dry

Cold and Dry

Warm and Wet

Cold and Wet

Nohria, JAMA 2002; 287: 628

Two-Minute Assessment of Haemodynamic Profile

Forrester’s diagram

Car

diac

Ind

ex

Wedge pressure

Hypovolemic Shock

Normal

Cardiogenic Shock

PulmonaryEdema

18 mmHg

2.2

l/m

q

Diagnosis and initial treatment algorithm of AHFDiagnosis and initial treatment algorithm of AHF

ESC guidelines 2008

Gheorghiade M, Pang PS. JACC 2009; 53:557Gheorghiade M, Pang PS. JACC 2009; 53:557

Non-invasive haemodynamic evaluation (EF, SV, CI, PAPs…)Non-invasive haemodynamic evaluation (EF, SV, CI, PAPs…)

Preload

LV end-Diastolic Volume

Afterload

LV end-Systolic Volume Heart

Rate

Cardiac Output

SystemicPressu

reContractili

ty

Systemic Periphera

l Resistanc

e Stroke Volum

e

=

AHF treatment strategy according to systolic blood pressureAHF treatment strategy according to systolic blood pressure

ESC guidelines2008

LV end-diastolic volume - LV end-systolic volume= STROKE VOLUME ???LV end-diastolic volume - LV end-systolic volume= STROKE VOLUME ???

Inotropes with vasodilator properties should be

reserved for those pts with

low-output state (low BP with

organ hypoperfusion),

who don’t respond to

other therapies.

Inotropes with vasodilator properties should be

reserved for those pts with

low-output state (low BP with

organ hypoperfusion),

who don’t respond to

other therapies.

Inotropic agentsInotropic agents

•Improves cardiac contractility by binding to Troponin C in cardiomyocytes•Significant vasodilation through ATP-sensitive potassium channels•Mild PDE inhibitory action

•Improves cardiac contractility by binding to Troponin C in cardiomyocytes•Significant vasodilation through ATP-sensitive potassium channels•Mild PDE inhibitory action

CO and SV

PCWP

CO and SV

PCWP

ESC Guidelines 2008

Dopamine: cl IIb, Level Evidence C

Dobutamine: cl IIa, Level Evidence B

PDEIs: cl IIb, Level Evidence B

Levosimendan: cl IIa, Level Evidence B

Inotropic agentsInotropic agents

Several inotropic agents are currently available for AHFS; most of them do not

appear to be safe and effective; despite

significant improvement in the hemodynamic

profile, they have potential deleterious

effects on: Myocardium (increased myocardial

oxygen demand)Blood Pressure (hypotension)Renal Function (impairment)

Digoxin iv : cl IIb, Level Evidence C Digoxin iv : cl IIb, Level Evidence C

•Increasing cardiac output•Reduction of filling pressure•Slow ventricular rate in rapid AF

•Increasing cardiac output•Reduction of filling pressure•Slow ventricular rate in rapid AF

GUIDELINESGUIDELINES

AHF between Current Guidelines and Patient Needs…

AHF ConsiderationsIn elderly people comorbidities are the

rule.An overlapping is frequent between

comorbidities and precipitating factors.

NY Heart Failure Consortium, JACC 2004

ESC guidelines 2008

Comorbidities and precipitating factors of AHFComorbidities and precipitating factors of AHF

The Cardio-Renal SyndromeThe Cardio-Renal Syndrome

Gheorghiade M, Pang PS. JACC 2009; 53:557Gheorghiade M, Pang PS. JACC 2009; 53:557

ESC guidelines 2008

HEART FAILURE & RENAL FAILUREHEART FAILURE & RENAL FAILURE Terapheutical Approach Terapheutical Approach

Evaluation of anaemia and Evaluation of anaemia and electrolyteselectrolytes

Drug monitoring Drug monitoring Ultrafiltration:Ultrafiltration: -No responsiveness to conventional therapy -No responsiveness to conventional therapy

(moderate-severe RF with creatinine > 2,5- 3 mg/dl)(moderate-severe RF with creatinine > 2,5- 3 mg/dl)

-Emergency treatment in severe acute HF with fluid -Emergency treatment in severe acute HF with fluid overloadoverload

-Long-term treatment in pts who can’t undergo heart -Long-term treatment in pts who can’t undergo heart transplanttransplant

Costanzo MR, Maya E. et al. JACC 2007

Clinical effectsClinical effects Reabsorption of Reabsorption of

systemic and pulmonary systemic and pulmonary oedemaoedema

Haemodynamic stabilityHaemodynamic stability

Hyponatremia Hyponatremia

correctioncorrection Increase of diuresis, Increase of diuresis,

natriuresis and natriuresis and responsiveness to responsiveness to diureticsdiuretics

hormons (NA, PRA, hormons (NA, PRA,

Aldosterone)Aldosterone)

Removal of toxins and Removal of toxins and

mediators (citokins, mediators (citokins,

TNF) that impaired TNF) that impaired

myocardial and renal myocardial and renal

function (?)function (?)

60

80

100

120

Baseline End UF 24 h after

1,5

2

2,5

3

Baseline End UF 24 h after

*

L/min/m2 mmHg b/min

*Cardiac Index

Heart rate MAP

0

5

10

15

20

25

Baseline End UF 24 h after10

15

20

25

30

35

40

Baseline End UF 24 h after

mmHg mmHg

Right Atrial Pressure Wedge Pressure

Overcoming the spatial

competition between heart

and lungs

Haemodynamic effectsHaemodynamic effects

Courtesy of “CCM”Courtesy of “CCM”

Before UF After UF

Ultrafiltration vs. Furosemidein Moderate Heart Failure

Agostoni et al. Am J Med 1994

-3

-2

-1

0

1

2

3

0 1 2 3 4 30 90

day

Furosemide (n=8; 248 mg i.v.)

UF (n=8; 1710 ml)

kg

Body Weight Plasma Renin Activity

-40

0

40

80

120

160

0 1 2 3 4 90

%

day

* * ** * *

*

***

*

* **

*

* p<0.01 vs. day 0

HEART HEART FAILUREFAILURE

CHRONIC CHRONIC PULMONARY PULMONARY

DISEASESDISEASES

PATIENTPATIENT

HEART FAILURE AND COPDHEART FAILURE AND COPD

Clinical classification of AHF

ESC guidelines 2008

The level of excursion of the tricuspid valvular plane during systole (TAPSE) corresponds with RV ejection fraction (5 mm ~ 20% RVEF, 10 mm ~ 30% RVEF, 15 mm ~ 40% RVEF, and 20 mm

~ 50% RVEF).

Bleeker GB, Heart 2006

TAPSETricuspid Annular Plane Systolic Excursion

EVALUATION of SYSTOLIC RV PERFORMANCE

RV is fully involved in HF and its function is an important prognostic marker.

Evaluation of PAP and RV function can provide some indipendent predictors of mortality in HF.

Functional evaluation of RV = Fundamental !

Evaluation of Pts with HF

ESC guidelines 2008

Goals of treatment in AHFGoals of treatment in AHF

Goals of treatment in CHFGoals of treatment in CHF

•To reduce mortality

•To reduce morbidity

•Prevention

•To reduce mortality

•To reduce morbidity

•Prevention

Improving post-discharge outcomes is the most important goal in AHFSImproving post-discharge outcomes is the most important goal in AHFS

ESC guidelines 2008

Multidisciplinary approach

Multidisciplinary approach

The right drug at the right time + apropriate management of comorbidities!!!The right drug at the right time + apropriate management of comorbidities!!!

Thank youThank you

REVIVE II: Primary Endpoint (n=600)REVIVE II: Primary Endpoint (n=600)

10

20

30

0

60

Improved WorseUnchanged

P=.015

% P

atie

nts

Placebo

Levosimendan

Packer M, et al. Presented at AHA Scientific Sessions 2005

JAMA, May 2, 2007 – Vol. 297

SURVIVE SURVIVE

• Previous ADHF studies focused on single measurements Previous ADHF studies focused on single measurements of symptoms or hemodynamic improvementof symptoms or hemodynamic improvement

• REVIVE was a positive trial with a Clinical Composite Endpoint that assessed REVIVE was a positive trial with a Clinical Composite Endpoint that assessed benefit over 5 daysbenefit over 5 days

• Patient & Physician Global Assessments and Patient Assessment of Dyspnea all Patient & Physician Global Assessments and Patient Assessment of Dyspnea all support the outcome of the primary endpointsupport the outcome of the primary endpoint

• The safety and mortality profile of levosimendan can be explained in terms of the The safety and mortality profile of levosimendan can be explained in terms of the baseline characteristics (ie, blood pressure) of patients and the mechanism of the baseline characteristics (ie, blood pressure) of patients and the mechanism of the drugdrug

• The higher Mortality Risk was observed in the Levosimendan low baseline blood The higher Mortality Risk was observed in the Levosimendan low baseline blood pressure cohortpressure cohort

• The SURVIVE trial demonstrated no survival difference between Levosimendan and The SURVIVE trial demonstrated no survival difference between Levosimendan and Dobutamine during long-term follow-up despite evidence for an early reduction of Dobutamine during long-term follow-up despite evidence for an early reduction of plasma BNP level for Levosimendan. plasma BNP level for Levosimendan.

• These findings may be related to:These findings may be related to: - the short duration of treatment in the trial;- the short duration of treatment in the trial; - a selective effect of Levosimendan in specific subgroups;- a selective effect of Levosimendan in specific subgroups; - the lack of a true difference between the two drugs. - the lack of a true difference between the two drugs. • Further studies are needed to distinguish between these possibilities.Further studies are needed to distinguish between these possibilities.

SURVIVE SURVIVE ConclusionsConclusions

REVIVE REVIVE ConclusionsConclusions