SHA24/033001

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the company/ companies listed below that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

Affiliation/Financial Relationship

Company

•

Grant/Research Support

• • • • • •

Bayer Boehringer Ingelheim Novartis Roche Servier Iroko

•

Consulting Fees/Honoraria

• • • •

Bayer Boehringer Ingelheim Roche Servier

Heart Failure The 5 most relevant points from the new ESC Guidelines Roberto Ferrari

What is new?

• Expanded indication for mineralocorticoid (aldosterone) receptor antagonists (MRAs).

• New indication for the sinus node inhibitor ivabradine.

• Expanded indication for resynchronization therapy (CRT).

• New role of coronary revascularisation in systolic HF. • Recognition of the growing use of ventricular assist devices (VADs).

Mineral Corticoid Receptor Antagonist RALES:

Spironolactone in severe HF (NYHA III – IV)

EPHESUS: Eplerenone in post MI and LVD or HT EMPHASIS: Eplerenone in mild HF (NYHA II – III) on top of contemporary treatment

RALES

Randomized ALdactone Evaluation Study Death / CV hospitalisation 1.00 0.90 30% risk reduction 0.80

Spironolactone

0.70 0.60

Placebo

0.50 0.00 0

3

6

9 12 15 18 21 24 27 30 33 36 Months Pitt et al. NEJM 1999

Cumulative Kaplan-Meier estimates of rates of the primary outcome and other outcomes, according to study group

N Eng J Med 364;1 January 2011

Initial pharmacological therapy

What is new?

• New indication for the sinus node inhibitor ivabradine.

• Expanded indication for resynchronization therapy (CRT).

• New role of coronary revascularisation in systolic HF. • Recognition of the growing use of ventricular assist devices (VADs).

If current in the sinus node: the determinant of HR Sinus node action potential and currents

Sinus node mV 0

500

ms

-50

pA

I -50 50

f

IK I CaL

Sinus node channels -50

I

CaT

-50

Ca channel T- type

f-channel -50 Ca channel L- type

K channel

Robinson RB, DiFrancesco D. Fundamental and Clinical Cardiology; NY; Marcel Decker; 2001:151-170.

I NaCa

Suppresssion of If current RR 0 mV

Heart rate reduction exclusively

-40 mV

-70 mV

Ivabradine

• 30% reduction of diastolic slope • other currents maintain pacemaker activity • safety factor of ivabradine

Objectives To evaluate whether ivabradine improves outcomes in patients with: 1 Moderate to severe chronic HF 2 LV ejection fraction ≤ 35% 3 Sinus rhythm, HR ≼ 70 bpm and 4 Recommended therapy

CV death or hospitalization for HF (%) 40

Placebo

HR = 0.82

p<0.0001

- 18%

30

Ivabradine

20

10

NNT for 1 year = 26 0 0

6

12

18

Months Swedberg K, et al. Lancet 2010;376: 875-885.

24

30

Hospitalization for HF (%) 30

Placebo

HR = 0.74

- 26%

p<0.0001 20

Ivabradine 10

0 0

6

12

18

Months Swedberg K, et al. Lancet 2010;376: 875-885.

24

30

Pre-specified subgroups Test for interaction

Age

<65 years ≥65 years

Sex

Male Female

Beta-blockers No Yes

Aetiology of heart failure Non-ischaemic Ischaemic

NYHA class

NYHA class II NYHA class III or IV

Diabetes No Yes

Hypertension No Yes

Baseline heart rate

p=0.029

<77 bpm ≥77 bpm

0.5

1.0 Hazard ratio

Favours ivabradine

1.5

Favours placebo

Pharmacological therapy â&#x20AC;&#x201C; next step

What is new?

• Expanded indication for resynchronization therapy (CRT).

• New role of coronary revascularisation in systolic HF. • Recognition of the growing use of ventricular assist devices (VADs).

CRT for severe HF: two pivotal trials COMPANION CV death or CV hospitalization Event free survival (%) 100 Medical therapy CRT-P p=0.002 80 CRT-D p<0.001

CARE-HF Death or CV hospitalization Event free survival (%) 100 Medical therapy CRT-P p<0.001 80

60

60

40

40

20

20

0

0 0

500

1000 Days

Bristow et al. Engl J Med 2004;350:2140-50

1500

0

500

1000

1500

Days Cleland et al. NEJM 2005

MADIT â&#x20AC;&#x201C; CRT Study (2009) Multicenter Automatic Defibrillator Implantation Trial

N Engl J Med. 2009 Oct 1;361(14):1329-38

RAFT

Resynchronised / Defibrillation for Ambulatory Heart Failure Trial

N Engl J Med 2010; 363:2385-2395

An expanded indication for cardiac resynchronisation therapy (CRT) Recommendations LBBB QRS morphology CRT, preferable CRT-D is recommended in patients in sinus rhythm with a QRS duration of > 130 ms, LBBB QRS morphology, and an EF <30%, who are expected to survive for > 1 year with good functional status, to reduce the risk of HF hospitalisation and the risk of premature death.

Non-LBBB QRS morphology CRT, preferably CRT-D should be considered in patients in sinus rhythm with a QRS duration of > 150 ms, irrespective of QRS morphology, and an EF <30%, who are expected to survive for > 1 year with good functional status, to reduce the risk of HF hospitalisation and risk of premature death

Class a

Level b

Ref c

I

A

154,155

IIa

A

154,155

QRS morphology, duration and effect of CRT CRT-D vs. ICD only HR for primary endpoint

Patients All

RAFT

MADIT-CRT

0.75 (0.64, 0.87)

0.66 (0.52, 0.84)

LBBB

QRS < 150 QRS ≥ 150

0.89 (0.60, 1.32) 0.51 (0.37, 0.69)

0.55 (0.35, 0.86) 0.41 (0.30. 0.56)

Non-LBBB

QRS < 150 QRS ≥ 150

1.24 (0.70, 2.19) 0.83 (0.47, 1.47)

1.41 (0.85, 2.32) 0.92 (0.52, 1.64)

Cardiac resynchronisation therapy (CRT): Summary 1. Expanded indication for patients with mild symptoms 2. Less certain about patients a) in atrial fibrillation b) with right bundle branchblock /IVCD (non-LBBB)

When to consider CRT and ICD

What is new? â&#x20AC;˘ New role of coronary revascularisation in systolic HF. â&#x20AC;˘ Recognition of the growing use of ventricular assist devices (VADs).

So, after STICH, should we perform revascularisation in all CAD patients with low EF ?

STICH Take home messages • CABG improves secondary outcomes

(CV death & all cause death + CV hospitalisations) but not all cause mortality in CAD patients with low EF < 35 %.

• Benefit more pronounced in very low EF< 27 %

• Viable myocardium (SPECT) is associated

with better survival but not if adjusted with confounders

New information on the role of coronary revascularisation in systolic HF Recommendations CABG is recommended for patients with angina and significant left main stenosis, who are otherwise suitable of surgery and expected to survive > 1 year with good functional status, to reduce the risk of premature death CABG is recommended for patients with angina and two or three vessel coronary disease, including a left anterior descending stenosis, who are otherwise suitable for surgery and expected to survive > 1 year with good functional status, to reduce the risk of hospitalisation for cardiovascular causes and the risk of premature death from cardiovascular causes

Class a

Level b

Ref c

I

C

-

I

B

191

What is new? â&#x20AC;˘ Recognition of the growing use of ventricular assist devices (VADs).

HeartMate II trial 200 patients, ineligible for transplantation. Randomised 2:1 continuous- vs. pulsatile-flow device. Mean age 64 years and mean LVEF 17%.

REMATCH

• LVAD or BiVAD indicated on top of E.B. therapy as a bridge to transplant (IB) or in selected patients (IIa B)

• To reduce symptoms and hospitalisation

Other news

• No more distinction between

systolic or diastolic HF but……just HF with or without preserved EF

• No further indication for HF with preserved EF

HFPEF Treatment effect on mortality Trial Name / Author

Relative Risk (95% CI)

ALLHAT - A ALLHAT - B ALLHAT - C CHARM - P DIG Hong Kong DHF Trial - A Hong Kong DHF Trial - B I-PRESERVE PEP - CHF SENIORS V-HeFT I - A V-HeFT I - B V-HeFT II Aronow et al. (1997)

1.19 (0.81, 1.75) 0.76 (0.49, 1.18) 0.90 (0.47, 1.72) 1.03 (0.87, 1.21) 1.00 (0.80, 1.25) 0.30 (0.03, 2.77) 0.16 (0.01, 2.98) 1.02 (0.91, 1.14) 1.06 (0.75, 1.51) 0.93 (0.65, 1.31) 1.31 (0.77, 2.24) 1.06 (0.59, 1.91) 0.65 (0.39, 1.09) 0.73 (0.58, 0.93)

Overall (95 % CI)

0.99 (0.92, 1.06)

Test for heterogeneity: l² =17.1%, P=0.267 Test for overall effect: P=0.699 0.1

Active Arm

1

10

Control Arm Holland et al., JACC, vol.57, 2011; 16:1676-86

Summary • ACEi + β-blockers + diuretics • If insufficient, addition of MRAs and Ivabradine (HR>70bpm)

• Consider CTR on the basis of

ECG and revascularisation on the basis of vitality

Summary â&#x20AC;˘ No further good news for HF and preserved EF

â&#x20AC;˘ Assist devices useful as bridge to transplantation

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