acute heart failure:therapeutic update
TRANSCRIPT
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Magdy El-Masry,MDProf. of Cardiology
Tanta Faculty of MedicineTanta,Egypt
Acute Heart Failure:Therapeutic Update
CardioEgypt 2014
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Algorithm for management of acute heart failure
Current therapeutic strategies
Novel therapeutic strategies
Newer inotropic drugs
New Recommendations for the Hospitalized Patient
Presentation Focus
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(i) Acute Decompensated HF :Worsening chronic HF or De novo HF
(ii) Pulmonary edema
(iii) Hypertensive AHF
(iv) Cardiogenic shock
(v) Isolated right HF
(vi) ACS and HF
Acute heart failure is a heterogeneous syndrome with multiple presentations
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Suggested initial triage in patients with suspected AHF syndromes
3%
50% 47%
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Suggested treatment algorithm for patients with hypertensive AHF syndromes.
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Suggested treatment algorithm for patients with normotensive AHF syndromes .
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Suggested treatment algorithm for patients with hypotensive AHF syndromes.
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What Should be the Goals of Therapy of AHF?
• Make the patient feel better: reduce dyspnea and improve QOL• Reduce Mortality• Reduce Rehospitalization• Do it safely
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Various targets for therapies used in the management of acute heart failure.
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Current Treatment of Acute Heart Failure
Diuretics
ReduceFluid
Volume(Na+&H20)
Vasodilators
DecreasePreloadand/or
Afterload
Inotropes
AugmentContract-
ility
88% 21% 15%
Use in ADHERE Registry
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Loop diuretics Vasodilators
Inotropics
MOST COMMON IV MEDICATIONS USED IN AHF
Used in 88% of cases 10% 1% 10%
6%6% 3%
?
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Novel therapeutic targets for thetreatment of acute heart failure
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Sites of action of drugs producing diuresis and natriuresis.
Rolofylline
Tolvaptan
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Sites of action of vasodilators.
NesiritideUlaritide
Relaxin
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Sites of action of inotropic agents.
Istaroxime
Levosimendan
Omecamtiv mecarbil
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Why do new agents fail in Phase III trials?
In recent years a repeated finding, particularly in clinical trials of patients with AHF, is that the positive results that are observed in preclinical and Phase II studies are not confirmed in large Phase III RCTs.
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A Word About Inotropes.
In the setting of AHF, inotropic agents are only recommended in patients with SBP > 90 mmHg and evidence of inadequate organ perfusion despite other therapeutic interventions.
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Intravenous Inotropic Agents Used in AHF
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Issues with Current Inotropes
Initial choice of therapy
Weaning
Patient related variables
Differences in efficacy
Adverse effect profile
Survival data
“Long-term” infusions
There is an urgent clinical need for agents that improve cardiac performancewith a favourable safety profile.
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Drugs Inotropic mechanism
Digoxin Sodium-potassium-ATPase inhibition
Dobutamine, dopamine b-Adrenoceptor stimulation
Enoximone, milrinone Phosphodiesterase inhibition
Levosimendan Calcium sensitization
Istaroxime Sodium-potassium-ATPase inhibitionplus SERCA activation
Omecamtiv mecarbil Acto-myosin cross-bridge activation
Gene transfer SERCA activation
Nitroxyl donor;CXL-1020
SERCA activation plus vasodilation
Ryanodine receptorstabilizer; S44121
Ryanodine receptor stabilization
Etomoxir, pyruvate Energetic modulation
Inotropic mechanisms and drugs
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Results of the recent AHF trials (disappointing)
Primary End Point Patients Study
Calcium Sensitizer (Levosimendan)Change CI 24 h and PCWP 24 h 203 LIDOMortality 30 d and Mortality 180 d
299 CASINO
Composite global assess. at 6 h, 24 h 5 d
600 REVIVE II
Mortality 180 d 800 SURVIVE
SERCA agonist & Na/K ATPase inhibitor (Istaroxime)PCWP Changes from baseline 120 HORIZON-HF
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Phase 2 testing offered disappointing data
This clinical trial was designed to evaluate an intravenous formulation of omecamtiv mecarbil in 613 patients hospitalized with acute heart failure.
The Phase 2 study did not meet its primary endpoint of dyspnea (shortness of breath) response but did show favorable dose- and concentration-related trends on dyspnea response
ATOMIC-AHF (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure) ESC Congress 2013 in Amsterdam
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Calcium sensitizersLevosimendan (Simdax®) increasessensitivity of troponin in the heartto calcium. This results in increased myocardial contractility. It is infusedi.v. for short treatment of AHF.
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Levosimendan : ESC Guidelines 2012
Patients with hypotension, hypoperfusion or shock
An i.v. infusion of levosimendan (or a phosphodiesterase inhibitor) may be considered to reverse the effect of ẞ-blockade if ẞ-blockade is thought to be contributing to hypoperfusion. • The ECG should be monitored continuously because inotropic
agents can cause arrhythmias and myocardial ischaemia, • and, as these agents are also vasodilators, blood pressure should be
monitored carefully.Class of recommendation IIb . Level of evidence C
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2013 ACCF/AHA Guideline for the Management of Heart FailureA Report of the American College of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines
Updated GuidelinesNew Recommendations for the Hospitalized Patient
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Worsening chronicheart failure (75%)
De novo heartfailure (23%)
Advanced/ end-stageheart failure (2%)
Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21Cleland JG et al. Eur Heart J. 2003; 24: 442
The Major Reason for Heart Failure Hospitalizations
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Therapies in the Hospitalized HF Patient
Recommendation COR LOE
HF patients hospitalized with fluid overload should be treated with intravenous diuretics
I B
HF patients receiving loop diuretic therapy, should receive an initial parenteral dose greater than or equal to their chronic oral daily dose, then should be serially adjusted
I B
New
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Therapies in the Hospitalized HF Patient
Recommendation COR LOE
When diuresis is inadequate, it is reasonable toa) Give higher doses of intravenous loop diuretics; or b) add a second diuretic (e.g., thiazide)
IIa B
New
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Therapies in the Hospitalized HF Patient
Recommendation COR LOE
Low-dose dopamine infusion may be considered with loop diuretics to improve diuresis
IIb B
Ultrafiltration may be considered for patients with refractory congestion
IIb C
Intravenous nitroglycerin, nitroprusside or nesiritide may be considered an adjuvant to diuretic therapy for stable patients with HF
IIb A
New
New
New
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Therapies in the Hospitalized HF Patient
Recommendation COR LOE
HFrEF patients requiring HF hospitalization on GDMT should continue GDMT unless hemodynamic instability or contraindications
I B
Initiation of beta-blocker therapy at a low dose is recommended after optimization of volume status and discontinuation of intravenous agents
I B
New
New
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Recommendations for Inotropic Support
Recommendations COR LOECardiogenic shock pending definitive therapy or resolution I C
Short-term support for threatened end-organ dysfunction in hospitalized patients withstage D and severe HFrEF
IIb B
Short-term intravenous use in hospitalized patients without evidence of shock orthreatened end-organ performance is potentially harmful
III:Harm B
New
New
New
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