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IX International Symposium
HEART FAILURE & Co.
Milano, 18 Aprile 2009
“Re-thinking acute heart failure approach”
Acute Heart Failure
Management between Current
Guidelines and Patient Needs
Susanna Sciomer - Francesco Fedele
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.
STROKE
VOLUME?
General clinical classification
Gheorghiade M, Pang PS. JACC 2009; 53:557
Acute Exacerbations Contribute to the
Progression of the Disease
With each event, myocardial injury may
contribute to progressive LV dysfunction
Worsening signs and symptoms,
Neurohormonal and renal abnormalities
Occurr soon after discharge
CHF
Functional ability
CHF
AHF
High post-discharge event
AHF
Time
Gheorghiade M et al. Am J Cardiol. 2005; 96 (6A)
ESC guidelines 2008
AHF between Current Guidelines and
Patient Needs…
GUIDELINES
Currently available
assessment modalities
combined with recent
advances in
cardiovascular
therapies provide
present-day
opportunities to
improve post-discharge
outcomes.
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.
Management of AHF and diagnostic problems
Gheorghiade M, Pang PS. JACC 2009; 53:557
Diagnosis is more likely in the presence of multiple typical symptoms and
signs (ex. dyspnoea, fatigue, third heart sound, oedema, raised jugular
venous pressure.....)
True typical symptoms?
The presence of several signs has a good specificity but a low sensibility
Need of instrumental objective data to assess the diagnosis
Need to exclude other pathologies
Two-Minute Assessment of
Haemodynamic Profile
Evidence for Congestion
(elevated filling pressures)
Normal
Pulmonary
Edema
Hypovolemic
Shock
Cardiogenic
Shock
2.2 l/mq
Cardiac Index
Forrester’s diagram
Orthopnea
High Jugular Venous Pressure
Increasing S3
Loud P2
Edema
Ascites
Rales (uncommon)
Abdominojugular Reflux
18 mmHg
Evidence for Low Perfusion
Narrow Pulse Pressure
Pulsus Alterations
May be Sleepy, Obtunded
ACE-inhibitor-Related
Symptomatic Hypotension
Declining Serum Sodium Level
Worsening Renal Function
Low Perfusion at Rest?
Wedge pressure
Congestion at Rest?
No
Yes
No
Warm and Dry
Yes
Cold and Dry
Warm and Wet
Cold and Wet
Nohria, JAMA 2002; 287: 628
Diagnosis and initial treatment algorithm of AHF
ESC guidelines 2008
Non-invasive haemodynamic
evaluation (EF, SV, CI, PAPs…)
Gheorghiade M, Pang PS. JACC 2009; 53:557
AHF treatment strategy according to systolic blood pressure
ESC guidelines
2008
Preload
=
Contractility
Afterload
Systemic
Peripheral
Resistance
LV end-Diastolic
Volume
Stroke
Volume
LV end-Systolic
Volume
Heart Rate
Systemic
Pressure
Cardiac
Output
LV end-diastolic volume
-
LV end-systolic volume= STROKE VOLUME ???
Inotropic agents
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.
•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
Inotropic agents
Dobutamine:
cl IIa, Level Evidence B
PDEIs:
cl IIb, Level Evidence B
Dopamine:
cl IIb, Level Evidence C
Levosimendan: cl IIa, Level Evidence B
Digoxin iv : cl IIb, Level Evidence C
ESC Guidelines 2008
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)
•Increasing cardiac output
•Reduction of filling pressure
•Slow ventricular rate in rapid AF
AHF between Current Guidelines and
Patient Needs…
GUIDELINES
AHF Considerations
In elderly people comorbidities are the rule.
An overlapping is frequent between
comorbidities and precipitating factors.
NY Heart Failure Consortium, JACC 2004
Comorbidities and precipitating factors of AHF
ESC guidelines 2008
The Cardio-Renal Syndrome
ESC guidelines 2008
Gheorghiade M, Pang PS. JACC 2009; 53:557
HEART FAILURE & RENAL FAILURE
Terapheutical Approach
 Evaluation of anaemia and
electrolytes
 Drug monitoring
Ultrafiltration:
-No responsiveness to conventional therapy
(moderate-severe RF with creatinine > 2,5- 3
mg/dl)
-Emergency treatment in severe acute HF with
fluid overload
-Long-term treatment in pts who can’t undergo
heart transplant
Clinical effects
 Reabsorption of systemic

and pulmonary oedema
Haemodynamic stability
 Hyponatremia correction
 Increase of diuresis,
natriuresis and
responsiveness to diuretics
  hormons (NA, PRA,
Aldosterone)
 Removal of toxins and
mediators (citokins, TNF)
that impaired myocardial
and renal function (?)
Costanzo MR, Maya E. et al. JACC 2007
Haemodynamic effects
L/min/m2
mmHg b/min
3
120
Cardiac Index
*
2,5
*
100
2
Heart rate
MAP
80
1,5
Before UF
After UF
60
Baseline
End UF
24 h after
mmHg
Baseline
End UF
24 h after
mmHg
40
25
35
20
Right Atrial Pressure
Wedge Pressure
30
15
25
10
20
5
15
0
10
Baseline
End UF
24 h after
Courtesy of “CCM”
Baseline
End UF
24 h after
Overcoming the
spatial competition
between heart and
lungs
Ultrafiltration vs. Furosemide
in Moderate Heart Failure
Body Weight
kg
Plasma Renin Activity
%
3
160
2
*
120
1
* p<0.01 vs. day 0
80
0
*
-1
*
40
0
-2
-3
0
* * *
1
2
3
* * *
4
UF (n=8; 1710 ml)
Furosemide (n=8; 248 mg i.v.)
30 90
day
*
*
*
*
1
2
3
*
*
4
90
-40
0
day
Agostoni et al. Am J Med 1994
HEART FAILURE AND COPD
HEART
FAILURE
PATIENT
CHRONIC
PULMONARY
DISEASES
Clinical classification of AHF
ESC guidelines 2008
EVALUATION of SYSTOLIC RV PERFORMANCE
TAPSE
Tricuspid Annular Plane Systolic Excursion
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
 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.
Evaluation of Pts with HF
Functional evaluation of RV = Fundamental !
Goals of treatment in AHF
Goals of treatment in CHF
•To reduce mortality
•To reduce morbidity
•Prevention
ESC guidelines 2008
Improving post-discharge outcomes is the most important goal in AHFS
The right drug at the right time +
apropriate management of comorbidities!!!
ESC guidelines 2008
Thank you
REVIVE II: Primary Endpoint (n=600)
60
Placebo
Levosimendan
% Patients
30
20
10
P=.015
0
Improved
Unchanged
Worse
Packer M, et al. Presented at AHA Scientific Sessions 2005
SURVIVE
JAMA, May 2, 2007 – Vol. 297
REVIVE Conclusions
•
•
•
•
•
Previous ADHF studies focused on single measurements
of symptoms or hemodynamic improvement
REVIVE was a positive trial with a Clinical Composite Endpoint that assessed benefit over 5
days
Patient & Physician Global Assessments and Patient Assessment of Dyspnea all support the
outcome of the primary endpoint
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 drug
The higher Mortality Risk was observed in the Levosimendan low baseline blood pressure
cohort
SURVIVE Conclusions
• The SURVIVE trial demonstrated no survival difference between Levosimendan and
•
•
Dobutamine during long-term follow-up despite evidence for an early reduction of plasma BNP
level for Levosimendan.
These findings may be related to:
- the short duration of treatment in the trial;
- a selective effect of Levosimendan in specific subgroups;
- the lack of a true difference between the two drugs.
Further studies are needed to distinguish between these possibilities.