canadian cardiovascular society heart failure guidelines
TRANSCRIPT
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
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
Canadian Journal of Cardiology Volume 33 2017
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
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
Canadian Journal of Cardiology Volume 33 2017
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
Canadian Journal of Cardiology Volume 33 2017
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.
Canadian Journal of Cardiology Volume 33 2017
PONTIAC study
• 65% relative risk reduction (RRR) in the primary combined event rate of hospitalization or death
due to cardiac disease at 2 years.
Canadian Journal of Cardiology Volume 33 2017
Canadian Journal of Cardiology Volume 33 2017
Selected Risk Markers for the
Development of Heart Failure
Canadian Journal of Cardiology Volume 33 2017
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
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]
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
Canadian Journal of Cardiology Volume 33 2017
Major Precipitants of Decompensation from Established
Heart Failure
Canadian Journal of Cardiology Volume 33 2017
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
Canadian Journal of Cardiology Volume 33 2017
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
Canadian Journal of Cardiology Volume 33 2017
Canadian Journal of Cardiology Volume 33 2017
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
Canadian Journal of Cardiology Volume 33 2017
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%
Moe GW, Ezekowitz JA et al., Can J Cardiol
Medications in HF: Patients
“Medications don’t work in patients who
don’t take them”
- C. Everett Koop
Moe GW, Ezekowitz JA et al., Can J Cardiol
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
Intracorporeal pumps.
Mary Ann Peberdy et al. Circulation. 2017;135:e1115-e1134
Copyright © American Heart Association, Inc. All rights reserved.
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