Andy Ignaszewski MD FRCPC Director, Heart Function Clinic PHC/UBC Vancouver, BC Canada

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1 Andy Ignaszewski MD FRCPC Director, Heart Function Clinic PHC/UBC Vancouver, BC Canada

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

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15 HF: The Fastest Rising Cardiovascular Condition In Canada Depending on the severity of symptoms, heart dysfunction, age and other factors, HF can be associated with an annual mortality of between 5% and 50% Up to 40% to 50% of people with congestive heart failure die within five years of diagnosis 1. Yeung et al., CMAJ 2012: 184 (14): E / 2. Bhatia RS, et al. N Engl J Med. 2006;355(3): / 3. Jong P, et al. Circulation. 2003;108:

Age (median) years Ischemic heart disease Hypertension Diabetes COPD Atrial fibrillation or flutter

16 The Typical HF Patient Is Older And Has Multiple Comorbidities Characteristics of patients hospitalized with a new diagnosis of heart failure 1997 (n=20,039) 52 % 51 % 2007 (n=17,262) % 36 % 26 % 25 % 23 % 28 % Age (median) years Ischemic heart disease Hypertension Diabetes COPD Atrial fibrillation or flutter Charlson-Deyo Comorbidity Index Score % 47 % 35 % 23 % 30 % 39 % Yeung et al., CMAJ 2012: 184 (14): E

Heart Failure Trajectory Palliative and Supportive Care Excellent Physical Function 1 2

initiated Plateau of variable length reached with initial medical management, or

$4 Stage D HF, with refractory symptoms and limited function Death Phase 5 End of life$ Time Sudden Death Event Transplant or Ventricular Assist Device Dotted lines represent

Time Sudden Death Event Transplant or Ventricular Assist Device Dotted lines represent

17 Heart Failure Trajectory Palliative and Supportive Care Excellent Physical Function Phase 1 Phase 2 Phase 3 Initial symptoms of HF develop and HF treatment is initiated Plateau of variable length reached with initial medical management, or following mechanical support or heart transplant Functional status decline with variable slope; intermittent exacerbations of HF that respond to rescue efforts 5 Phase 4 Stage D HF, with refractory symptoms and limited function Death Phase 5 End of life Time Sudden Death Event Transplant or Ventricular Assist Device Dotted lines represent sudden cardiac death that can occur anytime during the trajectory Goodlin SJ. J Am Coll Cardiol. 2009;54(5):

18 Reduced EF: Different Diseases With The Same Prognosis? Adjusted Survival Curves for Patients with Heart Failure with Reduced or Preserved Ejection Fraction during the Year after the First Hospital Admission HTN DM Survival (%) Preserved ejection fraction Preserved EF or Diast HF 75 Reduced ejection fraction Reduced EF or Syst HF Days Bhatia S, Liu P, et al., N Engl J Med 2006; 355:260-9

19 Change In Ejection Fraction (EF) For Patients With Preserved And Reduced EF HFpEF Ejection fractions do not remain the same forever they will change over time and therefore should be checked periodically (or at least thought about) as there is no predefined schedule for EF measurement Estimated EF (%) HFrEF Time After Diagnosis (years) Dunlay SM. et al. Circ Heart Fail. 2012;5(6):

20 HF Outcomes Unchanged Despite Advances In Medical Therapy The average lifespan of HF patients is 5.5 years 1 Approximately 1 in 4 HF patients is readmitted to the hospital within 1 year of discharge 2 Prognosis for HF patients remains poor with only slight improvements in overall mortality 3 In-hospital mortality rate* 1-year risk-adjusted mortality for outpatients** % 35.7% % 33.8% *p<0.1/**p< Alter DA, et al. J Gen Intern Med Sep;27(9): Lee DS, et al. Can J Cardiol. 2004;20: Yeung DF, et al. CMAJ. 2012;184(14):E

21 Current Challenges Associated With HF Care In Canada HF cannot be cured by relieving symptoms - Often progresses without signs or symptoms - Clinical focus has been to control symptoms Risk/Mismatch for patient care is common Patients discharged are often unprepared and unsupported - Patients unable to self-manage information overload - Frequent returns to emergency - 30-day readmission rates are high

22 Disease Progression Pathway For Heart Failure Stage A At high risk for HF but without structural heart disease or symptoms of HF. Stage B Structural heart disease but without signs or symptoms of HF. Stage C Structural heart disease with prior or current symptoms of HF. Stage D Refractory HF requiring specialized interventions. Patients have risk factors for the development of HF such as CAD, hypertension or diabetes mellitus but do not demonstrate impaired left ventricular function, hypertrophy, cardiac chamber enlargement, and are asymptomatic. Patients have evidence of left ventricular hypertrophy and/or left ventricular dysfunction, however are asymptomatic. Patients have evidence of left ventricular dysfunction and have either current symptoms of HF or have experienced symptoms of HF in the past. Patients have evidence of left ventricular dysfunction and severe symptoms of HF. Hunt SA, et al. Circulation. 2005;112(12):e

23 Time From First Diagnosis Of Chronic Heart Failure Until Consultation With A Cardiologist Proportion of patients who have not consulted Time since CHF diagnosis (days) Many patients with suspected new-onset CHF do not receive prompt cardiology care, as stipulated by current recommendations. Equity of access for women and those with lower socioeconomic status appears to be problematic Ehrmann FD, et al. Can J Cardiol Dec;25(12):

24 Risk Treatment Mismatch In the Pharmacotherapy Of Heart Failure Percentage Low risk Moderate risk 0 High risk 0 ACE ACE/ARB Beta Blockers Lee et al. EFFECT Study JAMA 2005;294:

25 CCS HF Algorithm Recommended Initial Referral And Wait Time Routine, Elective Referral Chronic HF disease management NYHA II NYHA I minimal or no symptoms See within 12 weeks, ideally within 6 Initial Referral Situational wait time benchmarks Initial Referral Urgency Semi-Urgent, Intermediate Risk New diagnosis of HF, stable, compensated NYHA II/III Worsening HF on therapy Mild symptoms with valvular or renal disease or hypotension Urgent New diagnosis of HF, not improving on therapy (unstable, decompensated) Progression to NYHA IV HF Post-hospitalization or ER visit for HF Severe HF with valvular or renal disease or hypotension Post myocardial infarction HF Emergent Acute severe myocarditis Rapidly progressive heart failure/cardiogenic shock Heart failure with ACS or MI Transplant and device evaluation of unstable patients New-onset acute pulmonary edema See within 4 weeks, ideally within 2 See within 4 weeks, ideally within 2 See within 24 hours Heart Failure Care Howlett JG et al. The Canadian Cardiovascular Society Heart Failure Companion: Bridging Guidelines to Your Practice. CJC 2015;1-15.

26 CCS HF Algorithm Recommended Follow-up Frequency Follow-up Frequency* High Risk Individual NYHA IIIb or IV symptoms Recent HF hospitalization During titration of HF medications New onset heart failure Complications of HF therapy (rising creatinine, hypotension) Need to down-titrate or discontinue beta-blockers or ACEi/ARB Severe concomitant and active illness (e.g. COPD, frailty) Frequent ICD firings (1 month) Intermediate Risk Individual No clear features of high or low risk. Low Risk Individual NYHA I or II No hospitalization in past year No recent changes in medications Receiving optimal medical/device HF therapies Follow-up every 1-4 weeks or as clinically indicated (remote monitoring possible for some titrations) Follow-up every 1-6 months Follow-up every 6-12 months Heart Failure Care Make inactive or consider for discharge from HF clinic if a minimum of 2 of the following characteristics are present: Stable NYHA I or II for 6-12 months On optimal therapies Reversible causes of HF fully controlled Having access to General Practitioner with expertise in management of HF Stable adherence to optimal HF therapy No hospitalization for >1 year LVEF >35% (consistently shown if more than one recent EF measurement) Primary care provider has access to urgent specialists reassessment *Visit frequency may increase during medication titration Howlett JG et al. The Canadian Cardiovascular Society Heart Failure Companion: Bridging Guidelines to Your Practice. CJC 2015;1-15.

Heart Failure Is A State Of Neurohormonal Imbalance As HF advances, the RAAS becomes the predominantly activated neurohormonal system Currently, marketed drugs target only the RAAS system However,

27 Heart Failure Is A State Of Neurohormonal Imbalance As HF advances, the RAAS becomes the predominantly activated neurohormonal system Currently, marketed drugs target only the RAAS system However, the NP system is counter-regulatory to the RAAS system in HF Physiological response NP system RAAS Pathophysiological response NPs Ang II Vasodilation Inactive fragments AT 1 receptor Vasoconstriction BP BP Sympathetic tone Aldosterone Fibrosis Hypertrophy HF symptoms/ progression Sympathetic tone Aldosterone Fibrosis Hypertrophy Natriuresis/diuresis Ang=angiotensin; AT1=angiotensin type 1; BP=blood pressure; NP=natriuretic peptide; RAAS=renin-angiotensin-aldosterone system Ferro et al. Circulation 1998;97: ; Levin et al. N Engl J Med 1998;339:321 8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42; Schrier et al. Kidney Int 2000;57: ; Schrier & Abraham. N Engl J Med 1999;341:577 85

28 Decline In Systolic Function Leads To Activation Of Three Major Neurohormonal Systems Sympathetic nervous system Natriuretic peptide system NPRs NPs Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy HF SYMPTOMS & PROGRESSION Ang=angiotensin; AT1R=angiotensin II type 1 receptor; HF=heart failure; NPs=natriuretic peptides; NPRs=natriuretic peptide receptors; RAAS=renin-angiotensin-aldosterone system Levin et al. N Engl J Med 1998;339:321 8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42; Kemp & Conte. Cardiovascular Pathology 2012; ; Schrier & Abraham. N Engl J Med 2009;341: Epinephrine Norepinephrine α 1, β 1, β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility Renin angiotensin aldosterone system Ang II Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis AT 1 R

Sustained Activation Of The RAAS Has A Detrimental Effect In HF Cardiac dysfunction leads to RAAS activation sustained activation puts further strain on the weakened heart, creating a vicious cycle

29 Sustained Activation Of The RAAS Has A Detrimental Effect In HF Cardiac dysfunction leads to RAAS activation sustained activation puts further strain on the weakened heart, creating a vicious cycle RAAS suppression as an effective strategy in treating HF ACEIs Hypertrophy Fibrosis Sympathetic tone Cardiac remodeling Myocyte necrosis Heart rate Contractility ACEIs ACE ARBs Sodium and water retention MRAs Blood volume Angiotensinogen Ang I Ang II Aldosterone Adrenal gland Direct renin inhibitors* Renin Vasoconstriction Hypertrophy Blood pressure ADH secretion Pituitary gland Water absorption Blood volume *Studies ongoing; not approved for treatment of HF ACE=angiotensin-converting enzyme; ACEI=angiotensin-converting-enzyme inhibitor; ADH=antidiuretic hormone; ARB=angiotensin receptor blocker; Ang=angiotensin; HF=heart failure; MRA=mineralocorticoid receptor antagonist; RAAS=renin-angiotensin-aldosterone system Zaman et al. Nat Rev Drug Discov 2002;1:621 36; Schrier, Abraham. N Engl J Med 1999;341:577 85; Brewster et al. Am J Med Sci 2003;326:15 24; Schmeider. Am J Hypertens 2005;18:720 30; McMurray et al. Eur Heart J 2012;33:

30 Mortality In HFrEF Remains High Despite The Introduction Of New Therapies That Improve Survival Reduction in relative risk of mortality vs. placebo ACEI* β-blocker* MRA* ARB* 16% (4.5% ARR; mean follow up of 41.4 months) SOLVD 1,2 34% (5.5% ARR; mean follow up of 1.3 years) CIBIS-II 3 30% (11.0% ARR; mean follow up of 24 months) RALES 4 17% (3.0% ARR; median follow up of 33.7 months) CHARM- Alternative 5 Survival rates in chronic HF have improved with the introduction of new therapies 1 However, significant mortality remains ~50% of patients die within 5 years of diagnosis 6 8 *On top of standard therapy at the time of the study (except in CHARM-Alternative where background ACEI therapy was excluded) patient populations varied between trials and as such relative risk reductions cannot be directly compared. SOLVD (Studies of Left Ventricular Dysfunction), CIBIS-II (Cardiac Insufficiency Bisoprolol Study II) and RALES (Randomized Aldactone Evaluation Study) enrolled chronic HF patients with LVEF 35%. CHARM-Alternative (Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity) enroled chronic HF patients with LVEF 40%. ACEI=angiotensin-converting-enzyme inhibitor; ARB=angiotensin receptor blocker; HF=heart failure; HFrEF=heart failure with reduced ejection fraction; LVEF=left ventricular ejection fraction; MRA=mineralocorticoid receptor antagonist 1. McMurray et al. Eur Heart J 2012;33: ; 2. SOLVD Investigators. N Engl J Med 1991;325: ; 3. Granger et al. Lancet 2003;362:772 6; 4. CIBIS-II Investigators. Lancet 1999;353:9 13; 5. Pitt et al. N Engl J Med 1999;341:709-17; 50; 6. Go et al. Circulation 2014;129:e28-e292; 7. Yancy et al. Circulation 2013;128:e ; 8. Levy et al. N Engl J Med 2002;347:

31 NEP Inhibition Must Be Accompanied By Simultaneous RAAS Blockade NEP metabolizes Ang I and Ang II via several pathways 1,2 Inhibition of NEP alone is insufficient as it is associated with an increase in Ang II levels, counteracting the potential benefits of NEP inhibition 2 Angiotensinogen Renin NEP Ang I ACE NEP Ang II AT 1 receptor Ang-(1 7) Inactive fragments NEP inhibition must be accompanied by simultaneous RAAS blockade (e.g. AT 1 receptor blockade) 2 Biological actions Signalling cascades Hypertrophy Fibrosis Vasoconstriction Hypertrophy Na + /H 2 O retention Aldosterone release Norepinephrine release Sympathetic tone ACE=angiotensin converting enzyme; AT1 = angiotensin II type 1; Ang=angiotensin; NEP=neprilysin; RAAS=renin angiotensin aldosterone system 1. Von Lueder et al. Circ Heart Fail 2013;6: ; 2. Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131 9

32 Simultaneous Inhibition Of Neprilysin And Suppression Of The RAAS With LCZ696 Has Complementary Effects LCZ696 Enhancing cgmp-mediated effects of natriuretic peptides Vasodilation Natriuretic and diuretic effects Proliferation Hypertrophy SNS outflow/sympathetic tone Aldosterone secretion Detrimental effects of vascular remodeling Suppressing RAAS-mediated effects Vasoconstriction Sodium and water retention Ventricular hypertrophy/remodeling Aldosterone secretion Cardiac fibrosis Sympathetic tone Systemic vascular resistance cgmp=cyclic guanosine monophosphate; RAAS=renin-angiotensin-aldosterone system; SNS=sympathetic nervous system Levin 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: Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131 9

33 PARADIGM-HF: Primary Endpoint: Death From CV Causes Or First Hospitalization For HF Cumulative probability Hazard ratio = 0.80 (95% CI: ) p<0.001 NNT to prevent one primary event: 21 HR: 20% difference favoring LCZ Enalapril LCZ696 Days since randomization No. at risk LCZ Enalapril *The numbers of patients who would need to have been treated (NNT) to prevent one primary event was evaluated over the duration of the trial McMurray et al. N Engl J Med 2014;371 (11):

34 PARADIGM-HF: Prospectively Defined Safety Events Event, n (%) Hypotension LCZ696 (n=4,187) Enalapril (n=4,212) p value 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) 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) 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 Fewer patients in the LCZ696 group than in the enalapril group stopped their study medication because of an Adverse Events (AE) (10.7 vs. 12.3%, p=0.03) McMurray et al. N Engl J Med 2014;371 (11):

35 PARADIGM-HF: Conclusions LCZ696 was more effective than enalapril in: - Reducing the risk of CV death and HF hospitalization - Reducing the risk of CV death - Reducing the risk of HF hospitalization - Reducing all-cause mortality - Incrementally improving symptoms and physical limitations LCZ696 was better tolerated than enalapril: - Less likely to cause cough, hyperkalemia or renal impairment - Less likely to be discontinued due to an adverse event - More hypotension, but no increased discontinuations - Not more likely to cause serious angioedema Interpretation - The effect of LCZ696 to stabilize the course of heart failure is likely to have important ramifications for both quality of life and resource utilization in this disorder 1. McMurray et al. N Engl J Med 2014;371 (11): ;

36 Relationship Between Changes In Heart Rate And Mortality In Studies On CHF 60 Profile 40 Xamoterol Change in mortality (%) Cibis Nor Timolol Mocha Gesica Bhat Anz Vheft (Prozosin) Solvd Consensus Vheft (Hdz/isdn) Promise -80 Us Carvedilol Change in heart rate (beats/min-1) Kjekshus and Gullestad. Eur Heart J Supplements 1999, Vol. 1 (Suppl H):H64-H69

37 Discharge HR And Risk Of Adjusted 30 Day Mortality In Patients With CHF N=9,097 Consecutive HF Patients Unadjusted Odds Ratio * Adjusted Odds Ratio <90 Discharge Heart Rate (bpm) <90 Discharge Heart Rate (bpm) p <0.05 p <0.01 * p <0.001 Habal, Liu, Lee. Circulation HF 2014; 7:12-20

Ivabradine Inhibits The I f Current R R 0mV -40mV Exclusive HR reduction

decreasing the depolarization slope and reducing heart rate.

impact on action potential threshold or shape. Thollon C et al.

38 Ivabradine Inhibits The I f Current R R 0mV -40mV Exclusive HR reduction -70mV Ivabradine inhibits the If current by blocking the I f channel, thus decreasing the depolarization slope and reducing heart rate. Ivabradine reduces spontaneous action potential frequency; there is no impact on action potential threshold or shape. Thollon C et al. Br J Pharmacol. 1994;112:37-42 DiFrancesco D., I(f) current and its inhibition Curr Med Res Opin 2005.

39 SHIFT Trial: Mean Heart Rate Reduction 90 HR = 0.82 ( ) p< Heart rate (bpm) Placebo Ivabradine Mean ivabradine dose: 6.4 mg bid at 1 month 6.5 mg bid at 1 year weeks Months Böhm M, et al. Lancet ;376(9744):

40 SHIFT Trial: Primary Endpoint CV Death Or Hospital Admission For Worsening CHF Cumulative frequency (%) HR = 0.82 ( ) p< Placebo Ivabradine 18% RRR Months Swedberg K, et al. SHIFT Investigators. Lancet. 2010;376(9744):

41 SHIFT Trial: Incidence Of relevant Serious AEs During The Study By System Organ Class Ivabradine group (n=3232) Placebo group (n=3260) p value Events Patients with an event Events Patients with an event All serious adverse events (45%) (48%) Cardiac disorders (28%) (30%) General disorders an administration site conditions (7%) (8%) Infection and infestations (7%) (7%) Nervous system disorders (4%) (5%) Respiratory, thoracic, and mediastinal disorders (3%) (4%) Surgical and medical procedures (3%) (4%) Gastrointestinal disorders (3%) (3%) Neoplasm (benign, malignant, and unspecified) (2%) (2%) Renal and urinary disorders (2%) (1%) Hepatobiliary disorders (1%) (1%) Eye disorders (1%) (<1%) 0.374

42 CCS HF Algorithm: Therapeutic Approach To Patients With CHF And Reduced Ejection Fraction Diuretics to relieve congestion Titrated to minimum effective dose to maintain euvolemia NYHA I Continue triple therapy NYHA I or LVEF <35% Continue present management Reassess every 1-3 years or with clinical status change Patient with LVEF <40% Triple Therapy ACEi (or ARB if ACEi intolerant), BB, MRA Titrate to target doses or maximum tolerated evidence-based dose Reassess Symptoms NYHA II-IV SR, HR 70 bpm ADD Ivabradine and SWITCH ACEi or ARB to LCZ696 for eligible patients Reassess Symptoms and LVEF NYHA I-III and LVEF 35% refer to ICD/CRT algorithm Consider LVEF reassessment every 1-5 years NYHA II-IV SR with HR 70 bpm or AF or pacemaker SWITCH ACEi or ARB to LCZ696 for eligible patients NYHA IV Consider: Hydralazine/nitrates Referral for advanced HF therapy (mechanical circulatory support/transplant) Advance HF referral Reassess as needed according to clinical status Non-pharmacologic therapies (teaching self care, exercise) Advance Care Plan and Documentation of Goals of Care

43 Multidisciplinary Approach To HF Management Primary care physicians Cardiologists Nurses Internists Pharmacists Patient Other specialists Dieticians Psychological support Caregivers Physiotherapists

44 Model For Future Disease Management Of HF From this To this! Heart Failure Clinic Heart Failure Clinic Patient with Heart Failure Other Care Provider HF Patient Family and community Primary Care Provider Primary Care Provider

45 Team Approaches And In-Person Communication Reduce HF Readmissions Hospital readmissions per month ** Hospital readmissions days per month -1.5 Single heart failure expert and telephone communication Single heart failure expert and in-person communication Team and in-person communication -2.9** -4.3* -6.4*** * p=0.06 ** p=0.05 *** p<0.001 Sochalski J, et al. Health Aff (Millwood) Jan-Feb;28(1):

46 Follow-up Cardiovascular Care Importance of Follow-up Care: A study of 3,136 patients in Alberta with Heart Failure found those who received regular cardiovascular follow-up visits with a family physician had better outcomes Kaplan Meier Survival Curves For Care Received, by Ambulatory Specialty Combined care (both specialist and family physician) Care by family physician only No follow-up care Cumulative Survival Log-rank = p< Days of Follow-up Ezekowitz JA, et al. Impact of specialist follow-up in outpatients with congestive heart failure. CMAJ 2005;172:

47 Compliance With Non-pharmacological Recommendations And Outcome In HF Patients % Overall non-compliant Cum survival Overall compliant Adjusted for age, NYHA functional class, stroke, diabetes, coronary artery disease, and previous HF admission HR 1.40 ( ); p= Pharmacological management Target-achieving management Lifestyle management Time to primary outcome Compliance with non-pharmacological recommendations is lower than with pharmacological 1 Patients non-compliant with the non-pharmacological recommendations had an increased risk for the composite endpoint of death or HF hospitalization 2 1. Ho TH. et al. PLoS One. 2014;9(4):e van der Wal MH, et al. Eur Heart J. 2010;31(12):

48 The Benefits Of Rehabilitation In HF Exercise-based cardiac rehabilitation programs for patients with HF improve: Exercise capacity Skeletal and respiratory muscle function Quality of life Autonomic function Biomarkers The Canadian Cardiovascular Society has adopted recommendations that physical activity be considered for stable patients with systolic dysfunction. Exercise programs also and reduce depressive symptoms as well as cardiovascular risk factors. McKelvie RS, et al. Can J Cardiol 2013;29(2):

49 Multidisciplinary HF Management Meta-Analysis Relative risk reduction achieved with multidisciplinary teams Mortality HF Hospitalizations All-cause Hospitalizations Relative risk reduction (%) -19% -25% -26% Duration of interventions in the pooled studies ranged from one visit to 30 months. McAlister FA et al. J Am Coll Cardiol 2004;44:810-9.

50 Impact Of Care At A Multidisciplinary Congestive HF Clinic: A Randomized Trial 1.00 Probability of not requiring readmission to hospital Intervention group Control group 0 p< Time (days) Ducharme A, et al. CMAJ. 2005;173(1):40-45.

51 CCS Guidelines Non-Pharmacological Management What Should HCPs Look For and Talk About? Talk to patients about their priorities Identify specific targets for therapy Look for, and treat, depression Discuss advance directives, living wills and substitute decision-makers Follow patients closely and systematically Educate about early warning signs of decompensation and how to respond Discuss salt and fluid intake Use daily morning weights with a diary and tailored prn diuretic dosing Measure supine and erect BP Follow creatinine and K+ closely Eliminate harmful drugs Arnold JMO, Liu P et al. Can J Cardiol 2006;22(1):23-45.

52 Conclusions HF is the fastest growing and most deadly CV condition in Canada M&M remains high New effective medical treatments are available sacubitril/valsartan ivabradine Best outcomes with multidisciplinary approaches

53 Sex With Patients Doctor Dave had sex with one of his patients and felt guilty all day long. No matter how much he tried to forget about it, he couldn't. The guilt and sense of betrayal was overwhelming. But every once in a while he'd hear an internal, reassuring voice that said: "Dave, don't worry about it. You aren't the first doctor to sleep with one of their patients and you won't be the last. And you're single. Just let it go.." But invariably the another voice would bring him back to reality, whispering... "Dave, you're a veterinarian..."

Sacubitril/Valsartan in HFrEF for All Protagonist View George Honos MD FRCPC FCCS FACC

Sacubitril/Valsartan in HFrEF for All Protagonist View George Honos MD FRCPC FCCS FACC Head of Cardiology Medical Manager / CV Program CHUM Disclosure Statement Within the past two years: I have had an