canadian cardiovascular society heart failure guidelines

Canadian Cardiovascular Society Heart Failure Guidelines: Top

Five Take-aways for the Family Physician

Miroslaw Rajda MD,FRCPDirector, Heart Function and Heart

Transplant ClinicApril05.2018

Learning Objectives

1. Discuss advances in the diagnosis and prevention of heart failure

2. Update knowledge and decision making

around risk assessment of patients and

optimal pharmacological and

nonpharmacological treatment options

Learning Objectives

3. Align heart failure prevention and treatment

strategies to integrate the new 2017 Canadian

Cardiovascular Society Heart Failure

Guidelines into daily clinical practice.

4. Advanced therapies and what you need to

know about therapeutic options for patients

with very advanced heart failure.

Conflict of Interest Disclosure

• Research – Novartis, Amgen, Servier, Janssen

• Advisory boards – Pfizer, Novartis, Roche,Servier

• CME’s – Novartis, Servier

www.ccs.ca

Introduction

• 600 000 Canadians have CHF

• 3080 admissions in 2015 in NS with diagnosis of CHF

• In hospital mortality 16.2% (2015 in NS)

• 30 day readmission rate 21% ( 2015 in NS)

• 1 year readmission rate 33.5% (2014 in NS)

• Median length of stay 9 days (2015 in NS)

Difficulties in Diagnosing“Heart Failure”

Can be a wide range of presentations

Many of the symptoms of heart failure overlap with other disease states such as COPD, obesity, nephrotic syndrome, drug- induced edema, cirrhosis and sleep apnea

Diagnosis of Heart Failure

Canadian Journal of Cardiology Volume 33 2017

Adapted from Burnett JC. J Hypertens. 2000;17(Suppl 1):S37-S43.

ANP = Atrial Natriuretic Peptide

BNP = B-type Natriuretic Peptide

CNP = C-type Natriuretic Peptide

Peptide Primary Origin Stimulus of Release

ANP Cardiac atria Atrial distension

BNP Ventricular myocardium Ventricular overload

CNP Endothelium Endothelial stress

Natriuretic Peptides:Origin and Stimulus of Release

• Synthesis

Synthesis in cardiac myocytes


Natriuretic Peptide Levels

“Breathing Not Properly” Study Maisel, Wu et al. NEJM 2002;347:161-7.

• 1586 patients presenting to the ED with

shortness of breath

• Data recorded: history, physical exam, lab

tests

• Initial assessment by ED physicians

• Followup assessment: 2 cardiologists with

access to all tests (echos), hospital course,

response to treatment, etc.

• BNP measured

Breathing not Properly Study

321 Patients with dyspnea (gold standard dx of CHF, pts with COPD with RHF dx with CHF).

Morrison LK et al. J Am Coll Cardiol. 2002;39:202-209.

0

100

200

300

400

500

600

700

800

900

1000

CHF COPD Asthma ActBronch

Pneumonia PE

Cause of Dyspnea

BN

P (

pg

/mL)

BNP Assay for DifferentiatingHeart Failure from Lung Disease

Heart failure outcomes Logeart et al. J Am Coll Cardiol 2004;43:635-641

Prevention of HF and Asymptomatic LV Dysfunction

• Screening to Prevent Heart Failure (STOP-HF)

• Patients with BNP >50 pg/ml – underwent ECHO and collaborative care

• Higher rate of RAAS inhibitors, fewer HF events and lower rate of hospitalization for HF


Prevention of HF and Asymptomatic LV

Dysfunction

• The NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease (PONTIAC) study used a cut point of NT-proBNP > 125 pg/mL to apply further cardiology consultation and individualized b-blockade and renin- angiotensin-aldosterone system uptitration.


PONTIAC study

• 65% relative risk reduction (RRR) in the primary combined event rate of hospitalization or death

due to cardiac disease at 2 years.


Selected Risk Markers for the

Development of Heart Failure


Prognostic Risk Scores

• Facilitate discussion about expectations and reasonable goals of therapy by incorporating objective measures into discussion

• Avoid relying on single, opinion-based prognostic factors

• Help plan approach to patient care moving forward

Risk ScoresScore Name Population Endpoint Other Considerations Access Variables

Seattle Heart Failure Model645

HFrEF Mortality risk at 1, 2 and 5 years with or without intervention. Mean life expectancy.

Restricted to clinical trial patients with ‘severe’ HF; Lab data entry non-SI units; More than 20 variables to enter.

https://depts.washington.edu/shfm/

Age, gender, NYHA class, weight, EF, SBP, ischemic etiology, diuretic dose, Na, lymphocyte count, Hgb, cholesterol, uric acid, use of ACEi/ARB/BB/aldosterone blocker/allopurinol/statins, QRS>120msec, use of device therapy

MAGGIC Risk Score646

HFrEF and HFpEF Mortality risk at 1 and 3 years

Cohorts from many sites; missing data in the overall analysis.

www.heartfailurerisk.org

Age, gender, NYHA class, diabetes, COPD, timing of diagnosis, EF, smoking, SBP, creatinine, BMI, use of beta-blocker/ACEi/ARB

3C-HF647 HFrEF and HFpEF Mortality risk at 1 year Patients from centres with experience with HF management; mostly Caucasian patients; Lab data entry in non-SI units.

http://www.3chf.org/site/home.php

Age, NYHA class, AF, valvular heart disease, EF, anemia, diabetes, hypertension, creatinine, use of ACEi/ARB or beta-blockers.

BCN- Bio-HF648 HFrEF and HFpEF Mortality risk at 1,2 and 3 years

Limited to patients with chronic HF treated in HF unit in a tertiary hospital. Lab data entry in US units. Use of biomarkers improves accuracy but is optional.

www.BCNBioHFcalculator.cat

Age, gender, NYHA class, Na, eGFR, Hgb, EF, diuretic dose, use of statins, beta-blockers or ACEi/ARB. Optional: hs-cTnT, ST2, Nt-pro-BNP

EFFECT649 Hospitalized HFrEF and HFpEF

30-day and 1-year mortality

Limited to hospitalized patients; missing current clinically important variables

http://www.ccort.ca/Research/CHFRiskModel.aspx

Age, respiratory rate, SBP, BUN, Na, CVD, dementia, COPD, cirrhosis, cancer, Hgb

EHMRG650 HFrEF and HFpEFpatients presenting to the ED

7 day mortality Limited to patients presenting to the ER and only short-term mortality; missing current clinically important variables

https://ehmrg.ices.on.ca

Age, arrival by ambulance, triage SBP, triage HR, triage O2 sat, potassium, creatinine, active cancer, metolazone, troponin. Optional: BNP

ELAN651 Hospitalized HFrEF and HFpEF

180-day mortality Limited to hospitalized patients Age, edema, SBP, serum sodium, serum urea, NYHA class at discharge, NT-proBNP at discharge and change in NT-proBNP

ADHERE652 HFrEF and HFpEF In-hospital mortality Limited to hospitalized patients BUN, creatinine, SBP

LACE653 Hospitalized patients 30-day mortality or readmission

Limited to hospitalized patients Length of stay, acute admission, comorbidity index, # of ED visits in last 6 months

2017 Guidelines: Prognostic risk scores

http://depts.washington.edu/shfm/index.php

• Insert age, gender, weight, EF, systolic BP, NYHA class level, medications and lab data

• Graph will appear showing mortality risk over 1,2, and 5 years

Seattle Heart Model

http://depts.washington.edu/shfm/index.php

Seattle Heart Model

• The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) Risk Calculator assigns an integer score based on heart failure risk factors to predict mortality at 1 and 3 years.

• Can be used in heart failure patients with reduced or preserved ejection fraction (EF).

• Not yet externally validated for patients with reduced EF.

• Excludes biomarkers known to correlate with mortality, such as B-type natriuretic peptide.

MAGGIC Risk Calculator for Heart Failure

From: Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studiesEur Heart J. 2012;34(19):1404-1413. doi:10.1093/eurheartj/ehs337Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: [email protected]

MAGGIC Risk Calculator for Heart Failure

From: Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studiesEur Heart J. 2012;34(19):1404-1413. doi:10.1093/eurheartj/ehs337Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: [email protected]

• Prognostic risk scores have a role in patient care to better define expectations, goals of therapy and a care plan

• Where possible, risk scores should be incorporated into practice and used to convey risk to patients

• Scores also useful in discussions between clinicians to adequately characterize the overall risk of a patient and determine a consistent treatment plan

2017 Guidelines: Prognostic risk scores

Moe GW, Ezekowitz JA et al., Can J Cardiol

HF Management

Medications

Risk factor modification

Procedures

Self-care

Device therapy

Multidisciplinary team

Ezekowitz, CMAJ, 2005, 172, 189

Lack of continuity of care leads to worse outcomes 1/3 of patients have no follow-up

0%

5%

10%

15%

20%

25%

30%

35%

40%

GP + Spec Spec GP No FU

Mo

rtal

ity

30-day mortality

1-year mortality

Consultation within 1 year post HF hospitalization 42% 1% 24% 34%

GP + Spec Spec GP No follow-up

Clinical Approach to CHF: Consider etiology

Identify triggers

Exclude ischaemia

General measures

Symptomatic therapy

Prognostic therapy

CHF Therapy

Etiology of HF – which investigation


Major Precipitants of Decompensation from Established

Heart Failure


Non-Pharmacological Management

Regular physical activity is recommended for all patients with stable symptoms and impaired LV systolic function

Before starting a training program, all patients should have a graded exercise stress test to assess functional capacity, ischemia, and optimal heart rate


Non-Pharmacological Management

All patients with symptomatic HF should not add salt to their diet and patients with advanced HF should reduce salt to <2 g/day

Daily morning weight should be monitored in HF patients

Restriction of daily fluid intake to 1.5-2 L/day should be considered for patients with fluid retention or congestion


1. McMurray et al. Eur Heart J 2012;33:1787–847; 2. SOLVD Investigators. N Engl J Med 1991;325:293–302; 3. CIBIS-II Investigators. Lancet 1999;353:9–13;

4. Zannad et al. N Engl J Med 2011;364:11-21; 5. Granger et al. Lancet 2003;362:772–6; 6.

Mortality of HF patients has improved with contemporary

therapies, but residual risk remains high

Re

ductio

n in

re

lative

ris

k

of

mort

alit

yvs.

pla

ce

bo

ACEI* β-blocker* MRA*ARB*

16%(4.5% ARR;

mean follow-up

of 41.4 months)

SOLVD 1,2

17%(3.0% ARR;

median follow-up

of 33.7 months)

CHARM-

Alternative5

34%(5.5% ARR;

mean follow-up

of 1.3 years)

CIBIS-II3

24%(3% ARR;

median follow-up

of 27 months)

EMPHASIS-HF4

Ivabradine selectively inhibits the If current

DiFrancesco, Drugs 2004; 64 (16): 1757-1765

R R

If current

Heart rate reduction

Slows diastolic depolarization slope

ΔRR

Ivabradine

If is the main current of diastolic depolarization that leads to the generation ofa new potential action

Sinus node

18 years

Class II to IV NYHA heart failure

Ischaemic/non-ischaemic aetiology

LV systolic dysfunction (EF 35%)

Heart rate 70 bpm

Sinus rhythm

Documented hospital admission for worsening heart failure 12 months

Inclusion criteria for SHIFT

Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81.

Chronic HF background treatment

89 91

84

61

22

3

90 91

83

59

22

4

0

10

20

30

40

50

60

70

80

90

100

Beta-blockers ACEIs and/orARBs

Diuretics Aldosterone antagonists

Digitalis ICD/CRT

Ivabradine

Placebo

Patients (%)

Effect of ivabradine on primary outcome

CV death or hospitalization for HF

0 6 12 18 24 30

40

10

0

Hazard ratio=0.76

P<0.0001

Pati

ents

wit

hp

rim

ary

com

po

site

en

d p

oin

t (%

)

Time (months)

20

30

Placebo

Ivabradine

www.shift-study.comBöhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

Ivabradine

Selective heart rate lowering drug with early clinical benefits on top of recommended therapy

By reversing cardiac remodeling - LV volumes & LVEF

With a good safety and tolerability profile whatever the background therapy across various patient profiles

Reduction of CV mortality and HF hospitalization by 18%

Reduction mortality by

Reduction HF hospitalization by 26%

The higher the heart rate at baseline, the greater the benefits

17% (all-cause)17% (CV)39% (HF)

Patients heart rate ≥ 75 bpm

PARADIGM-HF

Vasorelaxation

Blood pressure

Sympathetic tone

Aldosterone levels

Fibrosis

Hypertrophy

Natriuresis/diuresis

Inactive

fragments

Natriuretic and othervasoactive peptides*

AT1 Receptor

Vasoconstriction

Blood pressure

Sympathetic tone

Aldosterone

Fibrosis

Hypertrophy

Angiotensinogen(liver secretion)

Ang I

Ang II

RAAS

––

*Neprilysin substrates listed in order of relative affinity for NEP: ANP, CNP, Ang II, Ang I, adrenomedullin, substance P, bradykinin, endothelin-1, BNPLevin et al. N Engl J Med 1998;339:321–8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27–42;

Schrier & Abraham N Engl J Med 2009;341:577–85; Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131–9;Feng et al. Tetrahedron Letters 2012;53:275–6

ENTRESTO

Sacubitril (AHU377; pro-drug)

InhibitingEnhancing

LBQ657(NEP inhibitor)

OH

OHN

O

HO

O

Valsartan

N

NHN

N

N

O

OH

O

ENTRESTO simultaneously inhibits NEP (via LBQ657) and blocks the AT1 receptor (via valsartan)

PARADIGM-HF: Key inclusion criteria

McMurray et al. Eur J Heart Fail. 2013;15:1062–73

Chronic HF NYHA FC II–IV with LVEF ≤40%*

BNP (or NT-proBNP) levels as follows:

• ≥150 (or ≥600 pg/mL), or

• ≥100 (or ≥400 pg/mL) and a hospitalization for HFrEFwithin the last 12 months

≥4 weeks’ stable treatment with an ACEI or an ARB#, and a β-blocker

BP>100 mmHg

Aldosterone antagonist should be considered for all patients (with treatment with a stable dose for ≥4 weeks, if given)

*The ejection fraction entry criteria was lowered to ≤35% in a protocol amendment #Dosage equivalent to enalapril ≥10 mg/day

Characteristic*LCZ696 (n=4187)

Enalapril (n=4212)

Age, years 63.8 ± 11.5 63.8 ± 11.3

Women, n (%) 879 (21.0) 953 (22.6)

Ischemic cardiomyopathy, n (%) 2506 (59.9) 2530 (60.1)

LV ejection fraction, % 29.6 ± 6.1 29.4 ± 6.3

NYHA functional class, n (%)II III

2998 (71.6)969 (23.1)

2921 (69.3)1049 (24.9)

SBP, mmHg 122 ± 15 121 ± 15

Heart rate, beats/min 72 ± 12 73 ± 12

NT pro-BNP, pg/mL (IQR) 1631 (885–3154) 1594 (886–3305)

BNP, pg/mL (IQR) 255 (155–474) 251 (153–465)

History of diabetes, n (%) 1451 (34.7) 1456 (34.6)

Treatments at randomization, n (%)

Diuretics 3363 (80.3) 3375 (80.1)

Digitalis 1223 (29.2) 1316 (31.2)

β-blockers 3899 (93.1) 3912 (92.9

Mineralocorticoid antagonists 2271 (54.2) 2400 (57.0)

ICD 623 (14.9) 620 (14.7)

CRT 292 (7.0) 282 (6.7)

PARADIGM-HF: Summary of baseline characteristics

*mean ± standard deviation, unless statedMcMurray, et al. N Engl J Med 2014; ePub ahead of print: DOI: 10.1056/NEJMoa1409077.

Randomization

n=8442

PARADIGM-HF: Study design

*Enalapril 5 mg BID (10 mg TDD) for 1–2 weeks followed by enalapril 10 mg BID (20 mg TDD) as an optional starting run-in dose for those patients who are treated with ARBs or with a low dose of ACEI; †200 mg TDD; ‡400 mg TDD; §20 mg TDD.

McMurray et al. Eur J Heart Fail. 2013;15:1062–73; McMurray et al. Eur J Heart Fail. 2014;16:817–25;McMurray, et al. N Engl J Med 2014; ePub ahead of print: DOI: 10.1056/NEJMoa1409077.

2 Weeks 1–2 Weeks 2–4 Weeks

Single-blind activerun-in period

Double-blind Treatment period

On top of standard HFrEF therapy (excluding ACEIs and ARBs)

Median of 27 months’ follow-up

LCZ696 200 mg BID‡

LCZ696 100 mg BID†

Enalapril 10 mg BID*

Enalapril 10 mg BID§

LCZ696 200 mg BID‡

0

1

6

3

2

4

0

2

4

8

Enalapril(n=4212)

360 720 10800 180 540 900 1260Days After Randomization

4187

4212

3922

3883

3663

3579

3018

2922

2257

2123

1544

1488

896

853

249

236

LCZ696

Enalapril

Patients at Risk

1117

Kap

lan

-Meie

r E

sti

mate

o

fC

um

ula

tive R

ate

s (

%)

914

LCZ696(n=4187)

HR = 0.80 (0.73-0.87)

P = 0.0000002

Number needed to treat = 21

PARADIGM-HF: Primary endpoint

McMurray NEJM 2014

4187

4212

4056

4051

3891

3860

3282

3231

2478

2410

1716

1726

1005

994

280

279

LCZ696

Enalapril

Enalapril(n=4212)

LCZ696(n=4187)

HR = 0.84 (0.76-0.93)

P<0.0001

Kap

lan

-Meie

r E

sti

mate

of

Cu

mu

lati

ve R

ate

s (

%)

Days After RandomizationPatients at Risk

360 720 10800 180 540 900 12600

16

32

24

8

835

711

PARADIGM-HF: All cause mortality

McMurray NEJM 2014

Prospectively defined safety events

McMurray, et al. N Engl J Med 2014; ePub ahead of print: DOI: 10.1056/NEJMoa1409077.

• Fewer patients in the LCZ696 group than in the enalapril group stopped their study medication because of an AE (10.7 vs 12.3%, p=0.03)

Event, n (%)LCZ696

(n=4187)Enalapril(n=4212) p-value‡

Hypotension

Symptomatic 588 (14.0) 388 (9.2) <0.001

Symptomatic with SBP <90 mmHg 112 (2.7) 59 (1.4) <0.001

Elevated serum creatinine

≥2.5 mg/dL 139 (3.3) 188 (4.5) 0.007

≥3.0 mg/dL 63 (1.5) 83 (2.0) 0.10

Elevated serum potassium

>5.5 mmol/L 674 (16.1) 727 (17.3) 0.15

>6.0 mmol/L 181 (4.3) 236 (5.6) 0.007

Cough 474 (11.3) 601 (14.3) <0.001

Angioedema (adjudicated by a blinded expert committee)

No treatment or use of antihistamines only 10 (0.2) 5 (0.1) 0.19

Catecholamines or glucocorticoids without hospitalization 6 (0.1) 4 (0.1) 0.52

Hospitalized without airway compromise 3 (0.1) 1 (<0.1) 0.31

Airway compromise 0 0 ---

Entresto Initiation

• 36 hrs washout period for patients on ACE-inhibitors

• Reduction in diuretics dose

• Low dose Entresto for patients not on maximal guideline recommended doses of ACE inhib or ARB

• F/U in 2-4 wks with blood work

Mortality Benefit of Angiotensin Neprilysin Inhibition

System

10%

20%

30%

40%

ACEinhibitor

Angiotensinreceptorblocker

0%

% D

ecre

ase i

n M

ort

ality

16%

20%

Effect of ARB vs placebo derived from CHARM-Alternative trial

Effect of ACE inhibitor vs placebo derived from SOLVD-Treatment trial

Effect of LCZ696 vs ACE inhibitor derived from PARADIGM-HF trial

Angiotensinneprilysininhibition

17%


Medications in HF: Patients

“Medications don’t work in patients who

don’t take them”

- C. Everett Koop


Medications in HF: Providers

Medications don’t work in patients:

whose Health Care Professionals don’t prescribe them

whose HCP don’t prescribe them

optimally

whose HCP don’t prescribe them safely

Control: BP, Cr, K+, Na+

Indication: All patients without contraindication

Monitoring of the different treatments for HF and reducedejection fraction

Control: BP, Cr, K+, Na+Indication: Alternative to ACEI

Control: BP, HRIndication: All patients without contraindication

Control: BP, Cr, K+, Na+Indication: All patients without contraindication

Control: BP, Cr, K+, Na+

Indication: Replacement for ACEI or ARB in patients with stable chronic HF with reduced left ventricular ejection fraction NYHA Class II or III

Control: HRIndication: Patients with stable chronic HF with reduced left ventricular ejectionfraction (≤ 35%) NYHA Class II or III in SR and HR ≥ 77 bpm

ACEI

ARB

BB

MRA

ARNI

Ivabradine

Discontinuation of Treatment in HF

Additional Treatment Optionsin Heart Failure

Devices

• Defibrillators

• Biventricular Pacemakers(CRT)

Surgery

• Revascularization

• Valvular reconstruction

Mechanical circulatory support

IABP/LVAD

Transplantation

VAD Candidates

Decompensated end stage chronic

CHF

Post surgical shock

Acute myocarditis

Post AMI cardiogenic shock

Indications for VAD

• Bridge to transplant (BTT)

– most common

– allow rehab from severe

CHF while awaiting

donor

• Bridge to recovery (BTR)

– unload heart, allow

“reverse remodeling”

– can be short- or long-

term

• “Destination” therapy (DT)/Long-term devices

– permanent device, instead of transplant

– currently only in transplant-ineligible patients

• Bridge to candidacy (BTC)/Bridge to decision (BTD)

– when eligibility unclear at implant

– not true “indication” but true for many pts

Take Home Messages

• Biomarkers are very useful in diagnosing , monitoring and for prognosis of HF

• Prognostic risk scores are very helpful to communicate prognosis to the patients

• Triple therapy with B-blocker, ACE inhib/ARB and MRA is the mainstay of treatment for CHF

• New classes of medications are available(Lancoraand Entresto)

• MCS and heart transplant are available for selected patients with end-stage HF

canadian cardiovascular society heart failure guidelines

Documents