A CHALLENGE OF THE

ADVANCED HEART FAILURE

Prof. Davor Milicic, MD, PhD, FESC, FACC

University of Zagreb School of Medicine

Department of Cardiovascular Diseases

University Hospital Centre Zagreb

CROATIA

DISCLOSURES

• Conslultancies & lectures within last 2 y: Boerhinger Ingelheim, Merck, Pfizer, MSD, Sanofi Aventis, Pliva, Krka, Genzyme, Sandoz, Belupo, JGL, Astra Zeneca, Berlin Chemie Menarini, PharmaS, Medtronic, Medis Adria, Marck Medical

Heart failure -

the leading malignant disease!

PREVALENCE

0.4% - 3% total population

10% population over 65 y

PROGNOSIS

• Avarage

mortality

about 50%/ 5 y

• ADVANCED HF

• mortality 50%/ 1y

ADVANCED HF

• Acute or chronic

• Reversible: partially/completely

• Progressive: refractory..... terminal

• Terminal HF with life saving potential

• Terminal HF and MOF

TERMINAL heart failure:

–Refractory to maximal conventional treatment (drugs, CRT, AICD, ultrafiltration)

– Terminal phase of a malignant disease

IS THERE ANYTHING BEHIND THE WALL?

ADVANCED ..... END STAGE.........TERMINAL HEART FAILURE

HEART TRANSPLANTATION

● 1967. Christiaan N. Barnard, South Africa

● 1980. Cyclosporin (Stanford, USA)

● 30th September 1988 (Zagreb, Croatia). – 1st HTx in Eastern Europe,

● J. Sokolic, University Hospital Centre Zagreb, Croatia

HTx, University Hospital Centre Zagreb

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During the last 5 years > 1 Htx per month

Translpanted patients

10-y Survival, University Hospital Centre Zagreb

1988-1999 2000-2010

30 d: 85%

1 y: 80%

5 y: 64%

9 y: 54%

30 d: 73%

1 y.: 63%

5 y.: 49%

10 y: 35%

LIMITATIONS OF HTx

• Limited availability of donor hearts

• Patients on HTx lists die

• Problem of a possibly reversible advanced HF

• Problem of patients with temporary contraindication for HTx

• Problem of patients with absolute contraindication for HTx

• Solution: B R I D G I N G

Necessity of bridging

• Bridging to HTx

• Bridging to recovery

• Bridging to another bridge

• Bridging to final decision

No guidelines!

Bridging

• Pharmacological

• Non pharmacological• AICD/CRT

• Ultrafiltration, immunoabsorbtion

• Remote control

• Surgery

• Stemm cells

• VADs

• Total Arteficial Heart

0,4

0,5

0,6

0,7

0,8

0,9

1,0

0 30 60 90 120 150 180

Pro

bab

ility

of

Surv

ivin

g

Days Since Start of Study Drug Infusion

Levosimendan Dobutamine

SURVIVE : 180-Day All-Cause Mortality (levo vs.

dobutamine)

Overall 180-d

Mortality: 27%

Mebazaa JAMA 2007

New drugs on the horizon

ECE + NEP-Inhibitors(Daglutril)

New Natriuretic Peptides(Ularitide, Nesiritide, CD-NP)

Na+-K+ +SERCA-ATPase

Inhibitors(Istaroxime)

New Polypeptides(Relaxin)

AGE-Breakers(TRC 4185)

Renin-Inhibitors(Aliskiren)

Aldosterone-

Syntase-Inhibitors(LCI, FAD 286)

Myosine Activators(CK 1827-452)

sGC-Modulators(Cinaciguat, Riociguat, BAY 60-4552)

Early application of UF resulted in significant fluid removal

Bart et. al. JACC 2005;46:2043-2046 (n=40)

RAPID HF TRIAL

The UNLOAD trial

Primary End Point : Weight Loss at 48 H

Weig

ht

Loss (

kg)

Ultrafiltration Arm Standard Care Arm

P =.001

M = 5.0, CI + 0.68 kg

(N=83)

M = 3.1, CI + 0.75 kg

(N=84)

6 -

5 -

4 -

3 -

2 -

1 -

0 -

Costanzo MR et al. J Am Coll Cardiol. 2007;49:675-683.

STEMM CELLS results from trials

Randomised trials (AMI and/or HF)

• BOOST (nucl. BMC)

• REPAIR-AMI (monon. BMC)

• Lueven-AMI (lymphoc. BMC)

• ASTAMI (monon. BMC)

• FINCELL (monon. BMC)

• REGENT (monon. MBC)

• TOPCARE-CHD (mon. BMC)

• MAGIC (skeletal myoblasts)

Outcome

• EF (+); LVEDV (Ø)

• EF (+); LVEDV (Ø)

• Reg. EF (+); EF i LVEDV (Ø)

• EF i LVEDV (Ø)

• EF (+); LVESV i LVEDV (Ø)

• EF (+); LVESV i LVEDV (Ø)

• EF (+); LVEDV (Ø)

• LVEDV i LVESV (+); EF

Revascularization procedures

• The most common cause of HF is Coronary Artery Disease

• CAD is present in 60– 70% of patients with HF and impaired LVEF 1,2

• Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) should be considered in selected HF patients with CAD

1 Lloyd-Jones DM, Larson MG, Leip EP, Beiser A, D’Agostino RB, Kannel WB, Murabito JM, Vasan RS, Benjamin EJ, Levy D. Lifetime risk for developing conges- tive heart failure: the Framingham Heart Study. Circulation 2002;106:3068–3072. 2 Gheorghiade M, Sopko G, De Luca L, Velazquez EJ, Parker JD, Binkley PF, Sadowski Z, Golba KS, Prior DL,Rouleau JL, Bonow RO. Navigating the cross- roads of coronary artery disease and heart failure. Circulation 2006;114: 1202 – 1213.

Aortic valve surgery

• Aortic stenosis

– in eligible patients with HF symptoms and severe AS

– in asymptomatic patients with severe AS and impaired LVEF (<50%)

• Aortic regurgitation

– in all eligible patients with severe AR who have symptoms of HF

– in asymptomatic patients with severe AR and moderately impaired LVEF (LVEF<50%)

Mitral valve surgery

• Organic mitral regurgitation

– for patients with LVEF >30% (valve repair if possible).

– for patients with severe MR and LVEF<30% (medical therapy should be a first choice)

• Functional mitral regurgitation

– in patients with severe functional MR and severely depressed LV function, who remain symptomatic despite OMT

• Ischaemic mitral regurgitation

– in patients with severe MR and LVEF>30% when CABG is planned.

Non pharmacological Tx for AHFS

“General” and ICU Tx

PCI and surgical Tx

Mechanical Circulatory

Support (MCS)

“

Mechanical Circulatory Support (MCS)

• IABP

• ECMO/ECLS

• VAD

• TAH

INTRA-AORTIC BALLOON PUMP

Effects of IABP• Blood moves during diastole (when the pump inflates)

to the proxymal part of the aorta

• Pump deflation during systole reduces afterload by creating a vacuum effect

• Systolic pressure decrease by 20%• Aortic diastolic pressure increase by 30%• Mean arterial pressure increase• Heart rate reduction by 20% • Pulmonary capillary wedge pressure decrease by 20%• Cardiac output increase by 20 percent

Marchionni N et al. Effective arterial elastance and the hemodynamic effects of intraaortic balloon counterpulsation in patients with

coronary heart disease. Am Heart J. 1998;135(5 Pt 1):855.

IABP

• INDICATIONS :

– Acute Myocardial Infarction

– Ventricular arrhythmias

– Cardiogenic Shock

– Unstable Angina

– Cardiac Surgery

• CONTRAINDICATIONS :

• (Absolute Contraindications) :

– Aortic regurgitation

– Aortic dissection

– Severe peripheral vascular disease

– Complete cardiac arrest

• (Relative Contraindications) :

– Uncotrolled sepsis and bleeding diathesis

Klinika za kardijalnu kirurgiju KBC Zagreb

Extracorporeal Membrane Oxygenation

ECMO

Venoarterial:ECLS

Both provide respiratory support, but only VA ECMO provides hemodynamic support

Venovenous: ECMO

ECMO Outcomes

• VA ECMO provides acute support in patients incardiogenic shock

• ECMO is initiated until the patient recovers or being switched to VAD

• Several studies and case series reported survival rates of 20-43% among patients who received VA ECMO1-4

1 Younger JG et al. Extracorporeal resuscitation of cardiac arrest. Acad Emerg Med. 1999;6(7):700.1 Massetti M et al. Back from irreversibility: extracorporeal life support for prolonged cardiac arrest. Ann Thorac Surg. 2005;79(1):178.2 Kelly RB et al. Duration of cardiopulmonary resuscitation before extracorporeal rescue: how long is not long enough? ASAIO J. 2005;51(5):665.3 Combes A et al. Outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med. 2008;36(5):1404.4 Pagani FD et al. The use of extracorporeal life support in adult patients with primary cardiac failure as a bridge to implantable left ventricular assist device. Ann Thorac Surg. 2001;71(3 Suppl):S77.

Klinika za kardijalnu kirurgiju KBC Zagreb

PORTABLE ECMO

Maquet CardioHelp - ECMO, transportable

VAD - Options

LVAD RVAD BIVAD

VAD: classification

• Short term

• Medium term

• Long term

• Pulsatile

• Nonpulsatile

Survival to transplantation of patients supported by LVAD versus control (device unavailability or family

refusal)

J Thorac Cardiovasc Surg 2001: 122:1186-1195

ESC HF Guidelines, 2012

HeartMate II BTT – Hemodynamic and Functional Status Response

Miller LW, Pagani FD, Russell SD, et al. N Engl J Med 2007;357:885-96

Criteria for VAD selection

• Failure of one or two ventricles?

• Prediction of mechanical support duration

• Anticipation of final outcome

• Logistic circumstances

ESC HF Guidelines, 2012

CHALLENGE

• KEY QUESTION:

TERMINAL HF & LIFE SAVING POTENTIAL

versus

TERMINAL HF IN A TERMINAL PATIENT

Levitronix centrifugal, paracorporeal, short term support

in a 32 yo pt with DCM, Cardiogenic + septical shock, and MOF + HIT

1st successful bridge to heart transplant (BTT) at University Hospital Center Zagreb 2008.

University Hospital Centre

Zagreb,

HTX since 1988.

MCSsince 2008.

Short-term VADs

Levitronix Centrimag(continuous-flow, centrifugal-type rotaryextracorporal blood pump)

Availability : 30 days

Medtronic Biomedicus(centrifugal –type extracorporal blood pump)

Availability : 7 days

Medium- and Long-term VADs

Pulsatile flow, external (paracorpoeral) VAD

Availability – 6 to 12 months

Continuous flow, intracorporeal VADs

Availability – still not determined

HM-2

Heatrware

P-VAD

MCS: device selection algorithm at University Hospital Centre Zagreb

ACUTE & ADVANCED

REFRACTORY HF

POSTCARDIOTOMY NON-SURGERY RELATED

VAD (Biomedicus) or ECLS

VAD ( Levitronix)

PVAD / HeartMate

CARDIOGENIC

SHOCKREFRACTORY HEART

FAILURE

ECLS, IABP Levitronix

PVAD or HeartMateHTx or

“Destination”

Conclusion• No strict guidelines

• Cardiology and Cardiac Surgery

• Mandatory:

DEDICATED HEART TEAMS IN TERTIARY

CENTRES

• Right decision for the right patient in the right moment at the right place

• Universal goals: life prolongation and quality of life

Thank you!