State-of-the-Art: Treatment of Renal Dysfunction in Heart Failure. W. H. Wilson Tang, MD Cleveland Clinic, U.S.A.

Transcription

1 State-of-the-Art: Treatment of Renal Dysfunction in Heart Failure W. H. Wilson Tang, MD Cleveland Clinic, U.S.A.

2

3 Heart Failure Exacerbates Renal Insufficiency ADHERE Registry: Prevalence of CKD by egfr (in ml/min/1.73m2) Heywood et al, J Card Fail 2007 Racial & Cardiovascular Risk Anomalies Study: Risk of Heart Failure and Adverse Renal Outcomes George et al, Circ Heart Fail 2017

4 Cardio-Renal Disease : Then and Now The term comprises cases of combined cardiovascular and renal disease without such manifest predominance of either as to justify a prompt determination of the one element as primary and important and the other as secondary and unimportant Primary valvular or myocardial disease with secondary renal disease Primary arterial or arteriolar disease with secondary renal & myocardial disease Primary renal disease with secondary myocardial and vascular disease Stengel A, JAMA 1914 Ronco et al, EHJ 2009; Ronco et al, JACC 2009

5 Challenging Definition: Dynamic Renal Function Clinical/Renal Predictors: Hypertension Hepatojugular reflux egfr / BUN -blocker/spironolactone Cardiac Predictors: JVD LVEF RV dysfunction (RAP/PCWP) No central hemodynamic predictors Other Renal Measures: BUN Sodium or chloride Cystatin C Albuminuria Testani et al, AJC 2010; Testani et al, JCF 2011; Grodin et al, Am Heart J 2015

6 One-Size-Fits-All Approach in Acute HF Is Challenged Trial Drug/Population Differences ASCEND-HF (n=7141) Nesiritide to improve dyspnea/outcomes DOSE-AHF (n=308) Furosemide dose/route to improve dyspnea/outcomes CARRESS-HF (n=188) Ultrafiltration in WRF to improve dyspnea/outcomes PROTECT (n=2033) Rolofylline to prevent WRF and improve outcomes ROSE-AHF (n=360) Nesiritide/dopamine in CKD to prevent WRF RELAX-AHF (n=1161) Early serelaxin to improve dyspnea/outcomes BLAST-AHF (n=621) TRV027 to improve dyspnea/outcomes AVOID-HF (n= 224) Early ultrafiltration to improve dyspnea/outcomes TRUE-AHF (n=2157) Ularitide to improve dyspnea/outcomes TACTICS/SECRETS (n=507) Tolvaptan in acute HF to improve dyspnea/outcomes ATHENA-AHF (n=360) High dose spironolactone to improve serial NT-proBNP RELAX-AHF2 (n=6505) Early serelaxin to improve dyspnea/outcomes

7 Minimal Tubular Injury in Acute HF: Pseudo-AKI Neutrophil gelatinase associated lipocalin (NGAL) Dupont et al, Eur J Heart Fail 2012

8 Venous Congestion & Cardio-Renal Compromise RAP Mullens et al, JACC 2008 Iida et al; Tang et al, JACC Heart Failure 2016

9 Renal Responses to Raised Intravascular Volume Increase Renal Venous Impedance Index (VII) * p<0.01 Less Diuresis/Natriuresis with Higher VII Nijst et al, JACC-HF 2017

10 MEMs-Based Pressure Monitoring CHAMPION Study Inclusion: 550 NYHA III, HF hosp 12 months, egfr 25 ml/min, clopidogrel/warfarin x 1 month Abraham et al, Lancet 2011; Abraham et al, JCHF 2016

11 Relief of Intra-abdominal Pressure Transcatheter Renal Venous Decongestion (TRVD) Mullens et al, JACC 2008 Bartunek et al, EuroPCR 2016 (abstract)

12 Natriuretic Responses to Loop Diuretics Urinary Sodium and Furosemide Excretion during Diuresis in Acute HF Diuretic Efficiency = Net fluid output per doubling of furosemide equivalents Singh et al, J Card Fail 2014 Testani et al, JACC 2014 Rao et al, JASN 2017

13 Ultrafiltration for WRF: Neurohormonal Responses CARRESS-HF Ultrafiltration Bart et al, NEJM 2012; Kitai, Tang et al, Circ Heart Fail 2017

14 Cardio-Renal Dysregulation in HF Kim & Tang. In review 2017

15 Intersections between Neurohormonal, Sympathetic & Inflammatory Activation Urine Interleukin-6 Hanberg, Tang, Testani et al, Eur J Heart Fail 2017 (in press) Tissue Macrophages Fujiu et al, Nat Med 2017

16 Metabolic Disturbance: Gut Microbial TMA/TMAO Tang et al, JACC 2014; Tang et al, CircRes 2015; Organ et al, CircHF 2016; Suzuki et al, Heart 2016

17 Evidence on Chronic HF Therapy in CKD Most clinical trials excluded patients with egfr <30 ml/min/1.73m2 Damman, Tang, et al, JACC 2014

18 Targeting Sodium Handling at the Nephron Sodium-Glucose Co-Transporter (SGLT-2) inhibitors Chimeric Natriuretic Peptides Angiotensin Receptor Neprilysin Inhibitor (ARNI) Bodey et al, Int J Cardiol 2016; Voors, EJHF 2015; Wanner et al, NEJM 2016; Pan et al, PNAS 2009

19 Treatment of Renal Dysfunction in Heart Failure: A Sobering Conclusion We have pretty much taken care of patients with cardio-renal diseases the same way for the past half a century need to inspire new ideas/solutions: Recognizing LVEF and creatinine are flawed metrics for guiding therapy More precise/less iatrogenic approaches are needed to better: prevent/relief venous congestion while maintaining perfusion (hemodynamics) preserve natriuretic responses with adequate solutes/drugs (neurohormonal) Biological insights of cardio-renal interactions (e.g. inflammation/ metabolism) need to be translated to therapeutic solutions at the bedside