•Consulting Fees/Honoraria: •Novartis, AstraZeneca, Janssen, Servier, Amgen, Sanofi

Managingfluid, salt, K+ and creatininein heartfailureor cardiorenalsyndromeDR SERGE LEPAGECO CHAIR, HF UPDATEPASTPRESIDENT, QHFSU DE SHERBROOKE Conflict of Interest Disclosures-Serge Lepage, MD, FRCPC, CSPQ •Consulting Fees/Honoraria: •Novartis, AstraZeneca, Janssen, Servier, Amgen, Sanofi •Clinical Trials: •Novartis, Amgen 2 Learning objectivesFollowingthissession, participants willbebetterable to: •Understandthe interaction of diabetes, kidneydiseaseand HF•Reviewthe management of potassium, the "forgottenion"•Understandestablished& new modalitiesfor the treatmentof potassium disorders Electrolyte and FluidDisturbancesin Congestive HeartFailureNew topic? November 22, 1951N EnglJ Med 1951; 245:812-821 Normal Physiology HF Physiology ClinicalEvaluation of HF Sodium and HF Edemaand Sodium Hyponatremiasignsand symptomsmayinclude: •Nauseaandvomiting•Headache•Confusion•Lossof energy, drowsinessandfatigue•Restlessnessandirritability•Muscle weakness,spasmsorcramps•Seizures•Coma Correction of hyponatremia Treatmentrecommendationsfor symptomatichypernatremiaRecommendationsare as follows:•Establishdocumentedonset(acute, < 24 h; chronic, >24h)•In acute hypernatremia, correct the serumsodium atan initial rate of 2-3 mEq/L/h (for 2-3 h) (maximum total, 12 mEq/L/d).•Measureserumand urine electrolytesevery1-2 hours•Performserial neurologicexaminationsand decreasethe rate of correction withimprovementin symptoms•Chronichypernatremiawithno or mildsymptomsshouldbecorrectedata rate not to exceed0.5 mEq/L/h and a total of 8-10 mEq/d (eg, 160 mEq/L to 152 mEq/L in 24 h).•If a volume deficitand hypernatremiaare present, intravascularvolume shouldberestoredwithisotonicsodium chloridepriorto free-water administration. Distribution of Total Body K+ Intracellular fluid3,500 mEq (140-150 mEq/L)Muscle:2,700 mEqLiver:250 mEqErythrocytes:250 mEqBone:300 mEq Extracellular fluid70 mEq (3.5-5.5 mEq/L) HeartFailureand Potassium The PARADIGM‐HF trial suggestthe incidence of hyperkalemiawas≈16% over a medianfollow‐up time of 27months, despitea highlyselectedand carefullymonitoredclinicaltrial population. Hyperkalemiaisroutinelydefinedas a serumpotassium level>5mmol/L WRF: Worseningrenalfunction Poor Sensitivity and Specificity of ECG as Diagnostic Testfor Hyperkalemia •In 127 patients with serum K+between 6-9.3 mEq/L, only 46% of ECGs noted to have changes1 •In 90 cases, only 24 noted to have characteristic T-wave changesas read by a cardiologist2 •Only 1/14 who presented with arrhythmias or arrest had strict criteria2 1. Acker CG, et al. Arch Intern Med.1998;158:917-924.2. Montague BT, et al. ClinJ Am SocNephrol.2008;3:324-330. 048121620 6-6.16.2-6.46.5-6.76.8-7.17.2-9.4 Frequency Potassium Quintile Potassium quintiles by presence ofstrict criteria for ECG changes YesNo ECG, electrocardiogram. Goals of Therapy to Treat Acute Hyperkalemia Modified from FloegeJ, Johnson RJ, FeehallyJ, eds. Comprehensive Clinical Nephrology. St. Louis, MO: Mosby; 2010.Modified from Weisberg LS. CritCare Med.2008;36(12):3246-3251. K+Redistribution Redistribute Extracellular K+Into Cells K+Elimination Enhance the Elimination of K+From the Body Antagonize the Effects of K+on Excitable Cell Membranes Membrane Stabilization Therapies to Treat Acute Hyperkalemia 1.Modified from Weisberg LS. CritCare Med.2008;36(12):3246-3251. 2.Modified from FloegeJ, Johnson RJ, FeehallyJ, eds. Comprehensive Clinical Nephrology.St. Louis, MO: Mosby; 2010. 3.Ballantyne F 3rd, Davis LD, Reynolds EW Jr. Am J Physiol.1975;229(4):935-940. CPS, calcium polystyrene sulfonate; MOA, mechanism of action; SPS, sodium polystyrene sulfonate. K+Redistribution1,2K+Elimination1,2Membrane Stabilization1,2 Calcium gluconate salt↓ threshold potential of cardiac myocytes1 Hypertonic solution↑ action potential rising velocity of cardiac myocytes in hyponatremic, hyperkalemic patients3 InsulinActivates the Na+/K+-ATPase pump1 b-adrenoceptor agonistsMOA unknown1 Sodium bicarbonateAlkalinizes the urine, thereby enhancing urinary K+excretion1 Loop diureticsEnhance urinary K+excretion2 SPS/CPSEnhance K+removal through the colon3 HemodialysisRemoval of K+from blood1 ViforInnomar Lokelma AstraZeneca ?CADTH Hyperkalemia Is a Major Reason for Discontinuation of MRA•134 HF patients followed in a Portuguese HF clinic•Spironolactone use in patients with SCr≤2.5 mg/dLand K+ ≤5 mEq/L•25% of patients withdrew from spironolactone therapy (19/76) Severe hyperkalemia (≥6 mEq/L) occurred in 7 patients who withdrew from spironolactone therapy (9.2%).HF, heart failure; MRA, mineralocorticoid receptor antagonist; SCr, serum creatinine. 17.1%14.5% 5.3%1.3%0 10 20 30 Hyperkalemia Renal function decline Gynecomastia OtherReason for spironolactone suspension (%) Discontinuation of MRA % of Patients Serum Potassium Levels During the Randomized Phase (Days 8–29) According to Study Group KosiborodM, et al. JAMA.2014;312(21):2223-2233. Serum Potassium Levels During the Open-Label Phase (48 hours) KosiborodM, et al. JAMA.2014;312(21):2223-2233. Potassium Levels with Sodium Zirconium Cyclosilicate 10 g Once-Daily During Phase 2 From “SodiumZirconiumCyclosilicatein Hyperkalemia”, David K. Packham, 352, 3, 222-231 copyright © NEJM, Reprintedwith permission from Massachusetts Medical Society * * * * * * * * * * On Drug On Drug vs. Placebo Off Drug Serum Potassium (mmol/liter) 5.4 5.0 5.2 4.8 4.6 4.4 0.012345678910 20191817161514131211 21 Day Placebo (N=61) ZS-9, 10 g (N=63) *P<0.05 Initial Effect of Patiromeron Serum Potassium Level: AMETHYST-DN (52 weeks) Bakris G, et al. JAMA.2015;314(2):151-161. Drug Withdrawal Prognosis•Hyponatremiais an independent predictor of morbidity and mortality in CHF•Hypokalemia is an independent predictor of sudden cardiac death•Hyperkaliemiaismore prevalentthanusuallythoughtand oftenassociatedwithdiseasemodifyingdrugwithdrawal•Serummagnesiumisnot an independentriskfactor of deathin patients withmoderateto severeCHF Thank you !