Which I.V. therapies work

in HHF?

Gerasimos Filippatos, MD, FESC, FHFA

President

Heart Failure Association

NONE !!!

Outcome in acute HF is still poor

Death, Rehospitalization or ER visit

DOSE CARRESS-HF

40% at

60 days

All-cause death or hospitalization

Chronic HF: 17.2%

Acute HF: 35.1%

Days from enrollment

A. Maggioni, U Dahltrom, G, Filippatos et al EJHF2011

EURObservational Research Program:

The Heart Failure Pilot Survey

1-year all cause mortality:

acute HF – 16.8% chronic HF – 6.8%

Management of acute heart failure:

why so difficult ?

Clinical Factors:

Underlying causes: multifactorial, precipitating factor often

not identified

Clinical presentation: spectrum of various conditions,

heterogeneous pathophysiology

Cardiovascular and non-cardiovascular comorbidities

Pathophysiological targets: uncertain

End-points selection: not standardized

Courtesy of Piotr Ponikowski

Terminology

• HHF

• AHF

• ADHF

• WHF

• WCHF

• AHFS….

Recommendations for the treatment of acute

heart failure in HFA/ESC 2012 guidelines

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

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

Thrombosis/thromboembolism prophylaxis is recommended for patients

hospitalized with HF I B

Serum electrolytes, urea nitrogen, and creatinine should be measured

during the titration of HF medications, including diuretics I C

Goals of Treatment in Acute Heart Failure

Immediate

(ED/ICU/CCU)

Intermediate (in-hospital)

Long-term and pre-

discharge

management

Phases in the

AHF management

• Treat symptoms

• Restore oxygenation

• Improve organ perfusion &

haemodynamics

• Limit cardiac/renal damage

• Prevent thrombo-embolism

• Minimize ICU length of

stay

•Stabilise patient and

optimise treatment strategy

• Initiate and up-titrate

disease-modifying

pharmacological therapy

•Consider device therapy in

appropriate patients

• Identify aetiology and

relevant co-morbidities

• Plan follow-up strategy

• Enrol in disease

management programme,

educate, initiate appropriate

lifestyle adjustments

• Plan to up-titrate/optimize

disease-modifying drugs

• Assess for appropriate

device therapy

• Prevent early readmission

• Improve symptoms, quality

of life and survival

ESC /HFA Guidelines for the Diagnosis and Treatment

of Acute and Chronic Heart Failure 2012

Goals of Treatment in Acute Heart Failure

Immediate

(ED/ICU/CCU)

Intermediate (in-hospital)

Long-term and pre-

discharge

management Phases in the

AHF management

• Treat symptoms

• Restore oxygenation

• Improve organ perfusion &

haemodynamics

• Limit cardiac/renal damage

• Prevent thrombo-embolism

• Minimize ICU length of

stay

•Stabilise patient and

optimise treatment strategy

• Initiate and up-titrate

disease-modifying

pharmacological therapy

•Consider device therapy in

appropriate patients

• Identify aetiology and

relevant co-morbidities

• Plan follow-up strategy

• Enrol in disease

management programme,

educate, initiate appropriate

lifestyle adjustments

• Plan to up-titrate/optimize

disease-modifying drugs

• Assess for appropriate

device therapy

• Prevent early readmission

• Improve symptoms, quality

of life and survival

ESC /HFA Guidelines for the Diagnosis and Treatment

of Acute and Chronic Heart Failure 2012

Recommendations on Prehospital and Early

Hospital Management of AHF:

A consensus paper from the Heart Failure

Association of the ESC, the European Society

of Emergency Medicine and the Society of

Academic Emergency Medicine

EHJ and EJHF 2015: In Press

Important developments

Better use of old drugs

New Drugs

Treatment of co-morbidities

Diuretics in Hospitalized

Patients

ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

Decompensated chronic HF

• Consider higher dose of diuretics in

renal dysfunction or with chronic

diuretic use.

Diuretic Optimization Strategies

Evaluation in Acute Heart Failure (DOSE)

To evaluate the safety and efficacy of various initial strategies of furosemide

therapy in patients with ADHF

– Route of administration: • Q12 hours bolus

• Continuous infusion

– Dosing • Low intensification (1 x oral dose)

• High intensification (2.5 x oral dose)

Diuretics in Hospitalized Patients

If patients are already receiving loop diuretic therapy, the

initial intravenous dose should equal or exceed their

chronic oral daily dose and should be given as either

intermittent boluses or continuous infusion.

I IIa IIb III

EURObservational Research Programme

Heart Failure PILOT

Acute HF: persisting congestion at discharge and all-cause mortality during the follow-up

Pulmonary and/or

Peripheral congestion

MORTALITY

p<.0001

82.1%

24.0%

At admission At discharge

Determinants and forms of worsening renal function in heart failure.

Filippatos G et al. Eur Heart J 2013;eurheartj.eht515

What to do next ?

1. Increase furosemide dose

2. Ιntravenous infusion rather than bolus therapy

3. Substitution of an ineffective loop diuretic for another one

4. Add metolazone and/ or potasium sparing diuretic

5. Add dopamine at 2-5 mcg/k/m

6. Withdraw b-blocker and/ or ACE inhibitor

7. Add vasodilator

8. Add dobutamine

9. Add levosimendan

10. Add vasopressin antagonist ?

11. Start ultrafiltration

12. Start dialysis

13. Insert IABP

14. Insert another device

Maisel A, Filippatos G, Heart Failure. Jaypoor. Publishers, 2014

If symptomatic hypotension is absent, intravenous

nitroglycerin, nitroprusside or nesiritide may be considered

an adjuvant to diuretic therapy for relief of dyspnea in

patients admitted with acutely decompensated HF.

I IIa IIb III

ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012

Hasenfuss G and Teerlink J, EHJ 2011

Inotropic Therapies

Inotropic Support

Short-term, continuous intravenous inotropic support may

be reasonable in those hospitalized patients presenting

with documented severe systolic dysfunction who present

with low blood pressure and significantly depressed

cardiac output to maintain systemic perfusion and

preserve end-organ performance.

I IIa IIb III

MECHANISMS OF DISEASE PROGRESSION

Cardiac and Renal Injury Cell death by necrosis and apoptosis

Tn Release

Fibrosis

Progression

of Heart and

Kidney Failure

Neurohormonal

Activation

Hemodynamic

Deterioration

Modified from Filippatos G et al. Am J Physiol 1999

Acute Timeline

29

Conclusions

The IV drug therapy in acute HF has not changed

much in the last few decades

• only one drug in the USA and one drug in Europe have

been approved in the last 15 years

There is a need to identify treatment strategies

and regimens that reduce mortality and the

incidence of HF rehospitalization