Practical Points in Cardiorenal Syndrome

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Practical Points in Cardiorenal Syndrome Vichai Senthong, MD. Cardiovascular Unit, Faculty of Medicine Khon Kaen university HFCT Annual Scientific Meeting June 16, 2017, Eastin Grand Sathorn Hotel, Bangkok

Acute Heart Failure: 60-Day Readmission: 50% Patients with Inadequate Decongestion at Discharge: Are Know to be a Higher Risk of Admission and Mortality Each Readmission: Increased (Doubling) Mortality! Setoguchi S. et al. Am Heart J. 2007;154:260-66

Relief of Congestion is an Appropriate Target in the Treatment of Acute HF Diuretics Goal Adequate Decongestion (Dry and Warm) Method to Assessment Biomarker Guided Treatment NT-proBNP, hstnt, Hemoconcentration, or Transient Worsening Renal Function Shakar SF et al. Curr Treat Options Cardio Med (2014) 16:330;1-14

Current Goals for Decongestion Congestion Score: Based on Extent of Orthopnea, JVP, Edema (each on scale 0-3) Adequate Decongestion (Warm & Dry) Resolution of Orthopnea Trace to No Edema JVP of < 8 cm H2O Shakar SF et al. Curr Treat Options Cardio Med (2014) 16:330;1-14

The Clinical Course and Prognosis Value of Congestion: Finding from EVEREST trial Adequate Decongestion at Discharge is Associated with a Reduction in Readmission and Mortality Ambrosy AP. et al. Eur Heart J (2013) 34, 835-43

NO YES NO YES Signs/Symptoms Of Congestion Orthopnea/PND Elevated JVP Gut Congestion/Ascites Edema Rales Evidence of Low Perfusion Cold Sweated Extremities Mental Confusion Postural Hypotension Oliguria Stevenson LW. Eur J Heart Fail. 1999;1:251-57

Sequential nephron blockade Increasing diuretic dosage x Furosemide

Congestion is the Main Cause of HF Hospitalization Nieminen MS et al. Eur Heart J 2006 Nov;27(22):2725-36

Traditional Approach to Congestion in Heart Failure Diuretics (Furosemide) Relieve Symptom of Congestion and Edema

Diuretics in ADHF Limitations The Efficacy of diuretics to decrease mortality in HF has never bee established Diuretic Resistance Increased Mortality!

Diuretic Resistance in HF Definition Persistent Congestion despite adequate diuretic dose At least 80 mg of furosemide Cardiorenal Syndrome (CRS) Type 1: Acute CRS Acute Heart Failure leading to Worsening Renal Function (WRF) Cardiorenal Syndrome (CRS) Type 2: Chronic CRS Chronic Heart Failure leading to WRF Cardiorenal Syndrome (CRS) Type 3: Acute WRF leading to HF Cardiorenal Syndrome (CRS) Type 4: CKD leading to HF Cardiorenal Syndrome (CRS) Type 5: Systemic condition leading to simultaneous WRF and HF Neuberg GW, et al. Am Heart J 2002; 144:31-8 Ronco C, et al. Eur Heart J 2010;31:703-11

Pathophysiology of Cardiorenal Syndrome Low Cardiac Output?! Neuberg GW, et al. Am Heart J 2002; 144:31-8 Ronco C, et al. Eur Heart J 2010;31:703-11

Comprehensive analysis of the association between CI and renal function: 575 patients from ESCAPE trial, ESCAPE registry (PAC guided Tx) Advanced HF with LVEF 23 (+/-12) %, CI 2.3 (+/- 2.1) L/min/m2 Systolic BP <=125 mmhg, Creatinine <= 3.5 mg/dl Without Inotropic Drugs (Mirinone, Dopamine, or Dobutamine) Overall and Specific Subgroup Low LVEF <35% High RAP Low Systolic BP (<100 mmhg, 41%) More Impaired Renal (GFR <30) Hanberg JS, Testani JM, et al. J Am Coll Cardiol 2016; 67:2199-208

Does Increasing CO improve renal function? OPTIME-CHF Trial and ROSE-AHF Study that addresses this question Milrinone 0.5 mcg/kg/min vs Placebo Low-dose dopamine vs Placebo No difference in the rate of WRF between groups Klein et al. Circ Heart Fail 2008 Chen HH et al. JAMA 2013

Mullen W et al. J Am Coll Cardiol 2009; 53:589-96 and 2008; 51:300-6 patients admitted with ADHF Treated with Pulmonary Artery Catheter Guided Therapy Increased CVP is Associated with WRF Elevated IAP is associated with WRF CVP but not CI predicted WRF

Decongestion Strategy Wet&Warm Post hoc analysis DOSE-AHF trial ROSE-AHF trial CARRESS-HF trial Stepwise Pharmacological Care Algorithm (SPCA) Urine-output-guided diuretic adjustment VS Standard Decongestion Therapy SPCA: Greater in Decongestion, Without WRF Target = Adequate Decongestion (Warm&Dry) Dyspnea, Orthopnea: None Edema: Absent/trace JVP <= 8 cm H2O Grodin JL, et al. J Card Fail 2016;22:26-32

Stepwise Pharmacological Care Algorithm (SPCA) Adjust it to the next step in Table upward if UO is < 3L/day At 48-72 hours, Persistent Congestion (Wet&Warm) Low dose Dopamine/Dobutamine (2 ug/kg/min) NTG/Nesiritide Advanced Cardiorenal Therapy Grodin JL, et al. J Card Fail 2016;22:26-32

Decongestion Related WRF Does Not Alter Acute-HF Prognosis WRF/No Cong >> No WRF/Cong Metra et al, Circ Heart Fail 2012;5:54-62

Adequate Decongestion = Improved Renal Function Heart Failure Phenotype: Predominantly related to Congestive Renal Failure Phenotype How to identify Congestive Renal Failure Phenotype of HF? Clinical Findings: Venous Congestion (Elevated JVP), Acute CRS, Warm Response to Treatment Multimarker Biomarker Strategies Senthong, V. et al. Curr Heart Fail Rep. 2017; 14: 106-16

Intrarenal Venous Flow Pattern: A Window into Congestive Renal Failure Normal Continuous Intrarenal venous flow (IRVF) HF with Congestive Renal Failure DisContinuous Biphasic IRVF DisContinuous Monophasic IRVF Lida N, et al. J Am Coll Cardiol HF 2016; 4:674-82

HF Treatment one-size-fits-all approach HF Phenotype Personalized Approach >> one-size-fits-all Heart Failure with Congestive Renal Failure Senthong, V. et al. Curr Heart Fail Rep. 2017; 14: 106-16

Hemodynamic Stable HF 60% with Diuretic Resistance 80% NYHA III-IV Buckley et al, JACC Heart Fail 2016;4:1-8

Conclusion Congestion is the Main Causes of ADHF Venous Congestion (JVP,Gut Congestion) rather than reduced CO, may be the primary hemodynamic factor driving WRF in ADHF Congestive Renal Failure HypoTENSION HypoPERFUSION Diuretic Resistance: Increasing Diuretic Dosage Sequential Nephron Blockade with Different Diuretics Urine-output-guided diuretic adjustment Stepwise Pharmacological Care Algorithm (SPCA)

Thank You vichais@kku.ac.th