uResearchgrant:uAmgen , Novartis , SanofiuLecture feesuNovartis , Servier , Astra Zeneca , Bohringer Ingenheim , BayeruAd BoardsuAlnylam, Servier , Novartis , Bayer

Inotropes for HFREFHeart stimulation: Classifying the “tropes” of heart failureHe who wants a mule without fault, must walk on footDr Serge LepageHF Update 2020 Planning Committee Co-ChairHead, HeartFunctionClinicCIUSSS de l’Estrie CHUSMember, PrimaryPanel HF Guidelines Disclosure of Potential Conflicts of Interest uResearchgrant:uAmgen , Novartis , SanofiuLecture feesuNovartis , Servier , Astra Zeneca , Bohringer Ingenheim , BayeruAd BoardsuAlnylam, Servier , Novartis , Bayer Theoretical clinical characteristics of an ideal positive inotropic agentuEasytitration for rapidon/off effectuMyocardialoxygensupply/demandbalance uSteadyeffectin time (no tachyphylaxis) uDirect positive inotropiceffectuβ-independentpositive inotropicstimulation uFew or no arrhythmogeniceffectuNo intracellularcalcium overloaduMaintenance of the coronaryperfusion pressure uBeneficialeffectson regionalvascularbedsuReasonablebenefit/riskbalance Question 1uLow cardiacoutput isusualyassociatedwithall theseclinicalfeaturesexceptone u1: confusionu2: hypotensionu3: hepaticcongestionu4: oliguriau5: SvO2 < 65% Question 1uLow cardiacoutput isusualyassociatedwithall theseclinicalfeaturesexceptone u1: confusionu2: hypotensionu3: hepaticcongestionu4: oliguriau5: SvO2 < 65% Symptoms and signs of low perfusion vs. congestion in heart failure patients Question 2uLow cardiacoutput isusuallya signof decreasedleftventricularsystolicfunctionu1: Trueu2: False Question 2uLow cardiacoutput isusualya signof decreaseleftventricularsystolicfunctionu1: Trueu2: False Pathophysiologic mechanisms of low-output heart failure CCS guidelinesu2012: Inotropic agents have not been shown to improve patient outcomes.uOPTIME-HF No statistically significant benefit was found from the use of milrinone in terms of mortality or hospitalizations, whereas milrinone was linked to increased risk of prolonged hypotensive episodes and arrhythmias.23 In a subgroup analysis, milrinonewas associated with increased mortality rates in patients with HF of ischaemicaetiologyu2017: Consider Advanced HF management strategiesfor pts NYHA 3 or 4 with more then one of•LVEF < 25% and, if measured, peak exercise oxygen consumption < 14 mL/kg/min (or less than 50% predicted).•Evidence of progressive end organ dysfunction due to reduced perfusion and not to inadequate ventricular fillingpressures.•Recurrent HF hospitalizations ( 2 in 12 months) not due to a clearly reversible cause.•Need to progressively reduce or eliminate evidence based HF therapies such as ACEis, MRAs, or b-blockers, •because of circulatory-renal limitations such as renal insufficiency or symptomatic hypotension. •Diuretic refractoriness associated with worsening renalfunction.•Requirement for inotropic support for symptomatic relief or to maintain end organ function.•Worsening right HF (RHF) and secondary pulmonary hypertension.•Six-minute walk distance < 300 m.•Increased 1-year mortality (eg, > 20%-25%) predicted by HF riskscores•Progressive renal or hepatic end organ dysfunction.•Persistent hyponatremia(serumsodium < 134 mEq/L).•Cardiaccachexia.•Inability to perform activities of daily living. CCS guidelines 2017 ESC HF guidelines Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomisedclinical trials with meta-analysis and trial sequential analysis Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials 1854 patients were enrolled (904 patients in ESSENTIAL-I and 950 patients in ESSENTIAL-II). Levosimendanin Acute and Advanced Heart Failureresults for mortality and hospitalisations Levosimendanrevive study Question 3uInotropicsupport is:u1: a one size fitsallu2: as been provento improvesurvivalu3: shouldbetailoredto eachclinicalsituationu4: wouldpreferto askJonathan or Shelly Question 3uInotropicsupport is:u1: a one size fitsallu2: as been provento improvesurvivalu3: shouldbetaileredto eachclinicalsituationu4: wouldpreferto askJonathan or Shelly Subtypes of clinicalpresentation INTERMACS profiles and outcomes of ambulatory advanced heart failure patients: A report from the REVIVAL Registry The Journal of Heart and Lung TransplantationVolume 39, Issue 1, Pages 16-26 (January 2020) INTERMACS profiles and outcomes of ambulatory advanced heart failure patients: A report from the REVIVAL Registry The Journal of Heart and Lung TransplantationVolume 39, Issue 1, Pages 16-26 (January 2020) DOI: 10.1016/j.healun.2019.08.017 Figure 5 The Journal of Heart and Lung Transplantation2020 39, 16-26DOI: (10.1016/j.healun.2019.08.017) Copyright © 2019 International Society for Heart and Lung TransplantationTerms and Conditions INTERMACS profiles and outcomes of ambulatory advanced heart failure patients: A report from the REVIVAL Registry New classification:CalcitropesMyotropesMitotrophesInotropy produced by conventional agents, includingcatecholamines, phosphodiesterase-3 inhibitors, andcardiac glycosides (e.g., digitalis), all increasemyocardial force production by altering the concentrationof intracellularCa+Because myosin is the central actor of thesarcomere, therapeutics that target the myosin, actin,the associated regulatory proteins, or other structural elements of the sarcomere through calcium independentmechanisms Myocardial energetics are centered around mitochondrialenergyproduction, and drugs acting at themitochondria are therefore proposed to be calledmitotropes. COSMIC-HF trialThe Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF trial) was a randomised, parallel-group, double-blind, placebo-controlled phase II study conducted over 87 sites in 13 countries GALACTIC HF. The primary efficacy outcome is the time to cardiovascular death or first HF event. The study has 90% power to assess a final hazard ratio of approximately 0.80 in cardiovascular death, the first secondary outcome GALACTIC-HF Trialu8256 participantsuEstimated Primary Completion Date : January 27, 2021upharmacokinetic-guided dose titration strategyusing doses of 25, 37.5, or 50 mg twice daily. ConclusionsuWhenthe goinggetstoughuIn a PandemicuIn ADHFuYou have to reactuGivenappropriatelyuInotropes can improvehemodynamicsuWithminimal harmuNew mitoptopesand myotropesare cominguTo improvesymptomsuAnd hopefullyreducehospitalisations and mortality Thank youSerge Lepageserge.lepage@usherbrooke.caBe sure to follow us on Twitter! @CanHFSociety