Heart Failure and Renal Failure Gerasimos Filippatos, MD, FESC, FHFA President HFA
Definition Epidemiology Pathophysiology Management (?)
Recommendations for NHLBI in cardiorenal interactions related to heart failure The result of interactions between the kidneys and other circulatory compartments that increase circulating volume and symptoms of heart failure and disease progression are exacerbated. At its extreme, cardio-renal dysregulation leads to what is termed cardio-renal syndrome in which therapy to relieve congestive symptoms of heart failure is limited by further decline in renal function NHLBI Working Group. Cardio-renal connections in heart failure and cardiovascular disease: executive summary. Available at: http://www.nhlbi.nih.gov/meetings/workshops/cardiorenal-hf-hd.htm.
The New Definition of Cardiorenal Syndrome Cardiorenal Syndrome (CRS) General Definition: A pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ CRS Type I (Acute Cardiorenal Syndrome) Abrupt worsening of cardiac function (e.g. acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury CRS Type II (Chronic Cardiorenal Syndrome) Chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease CRS Type III (Acute Renocardiac Syndrome) Abrupt worsening of renal function (e.g. acute kidney ischaemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischemia) CRS Type IV (Chronic Renocardiac Syndrome) Chronic kidney disease (e.g. chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events CRS Type V (Secondary Cardiorenal Syndrome) Systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction Ronco C. et al, EHJ 2010
The Definition Any degree of cardiac dysfunction Any degree of kidney failure Iron Deficiency Any degree of anemia What defines the above factors?
The interaction between heart failure, renal dysfunction, anaemia, and iron deficiency. Macdougall I C et al. Eur J Heart Fail 2012;14:882-886
Classification of CKD Stage Description CreatClearance (ml/min/1.73m) 1 Early renal damage, ifother Markers of this (proteinuria or Structural abnormality) >90 2 Early renal insufficiency 60-89 3 Moderate renal failure 30-59 4 Severe renal failure 15-29 5 End stage renal disease <15 US National Kidney Foundation Classification. Am J Kid Dis 2002; 39: S1-246
Filippatos G et al. Eur Heart J 2014
Definition Epidemiology Pathophysiology Management (?)
From: Braunwald s Heart Disease. 9th ed. Philadelphia, Elsevier, 2011
Prevalence of renal dysfunction 60% of patients with egfr <60 ml/min egfr, ml/min/1.73 m2 Heywood et al., J Card Fail 2007; 13:422
Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure. Results from CHARM Low LVEF Preserved LVEF Hillege et al., Circulation. 2006;113:671-678
PROPORTION OF REMAINING IN STUDY BUN and Death or HF Rehospitalization 1.0 0.9 BUN < 18 mg/dl 0.8 BUN 19-26 mg/dl 0.7 BUN 27-39 mg/dl 0.6 0.5 Log-Rank Test P-Value = 0.0005 BUN > 40 mg/dl 0 10 20 30 40 50 60 70 DAYS IN STUDY Filippatos G et al.j Cardiac Failure 2007
Determinants and forms of worsening renal function in heart failure. Filippatos G et al. Eur Heart J 2013;eurheartj.eht515
Definition Epidemiology Pathophysiology Management (?)
cardiac output Hypotension Cardiac dysfunction systemic venous pressure ACEi/ ARBs Neurohormonal activation Renal hypoperfusion Renal dysfunction i.v. Furosemide Adenosine release Tubuloglomerular feedback Renal venous pressure Metra, Brutsaert, Dei Cas, Gheorghiade. IACC ESC Textbook, 2011
cardiac output Hypotension Cardiac dysfunction systemic venous pressure ACEi/ ARBs Neurohormonal activation Renal hypoperfusion Renal dysfunction i.v. Furosemide Adenosine release Tubuloglomerular feedback Renal venous pressure Metra, Brutsaert, Dei Cas, Gheorghiade. IACC ESC Textbook, 2011
Emerging Therapies in HF De Luca L, Mebazaa A, Filippatos G et al. Eur J Heart Fail 2008 Blocks adenosine mediated afferent arteriole vasoconstriction maintains GFR Inhibits reabsorption of sodium and water in the proximal tubule diuresis
MECHANISMS OF DISEASE PROGRESSION DRUG TOXICITY Cardiac and Renal Injury Cell death by necrosis and apoptosis Tn Release Fibrosis Progression of Heart and Kidney Failure RAAS Neurohormonal Activation Hemodynamic Deterioration Modified from Filippatos G et al. Am J Physiol 1999
Early drop in systolic blood pressure and worsening renal function in AHF: renal results of Pre RELAX AHF European Journal of Heart Failure vol 13, pages 961-967, 2014 DOI: 10.1093/eurjhf/hfr060
Early drop in systolic blood pressure and worsening renal function in AHF: renal results of Pre RELAX AHF European Journal of Heart Failure vol 13, pages 961-967, 2014 DOI: 10.1093/eurjhf/hfr060
Potential pathogenetic pathways linking heart failure with renal dysfunction. Filippatos G et al. Eur Heart J 2014
Definition Epidemiology Pathophysiology Management (?)
Heart Failure Drug Treatment Options Symptom Relieving Disease Modifying Diuretics Digoxin ACE inhibitors /angiotensin II receptor antagonists Beta-blockers Aldosterone receptor antagonists
Selected Placebo-Controlled Trials in Patients with Heart Failure: Renal Function of Participants and Medication Efficacy Shlipak, M. G. Ann Intern Med 2003;138:917-924
Treatment algorithm for patients with systolic heart failure, based on renal function Shlipak, M. G. Ann Intern Med 2003;138:917-924
ACE-I associated creatinine elevations Bakris GL et al. Arch Int Med 2000;160:685
Decompensated chronic HF Consider higher dose of diuretics in renal dysfunction or with chronic diuretic use. ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure
What to do next? 1. Increase furosemide dose 2. Ιntravenous infusion rather than bolus therapy 3. Substitution of an ineffective loop diuretic for another one 4. Add metolazone and/ or potasium sparing diuretic 5. Add dopamine at 2-5 mcg/k/m 6. Withdraw b-blocker and/ or ACE inhibitor 7. Add dobutamine 8. Add levosimendan 9. Start ultrafiltration 10. Start dialysis 11. Insert IABP 12. Insert another device Maisel A, Filippatos G, Heart Failure. Publisher Jaypoor Brothers, 2014
Renal Replacement Therapy I IIa IIb III Ultrafiltration may be considered for patients with obvious volume overload to alleviate congestive symptoms and fluid weight. I IIa IIb III Ultrafiltration may be considered for patients with refractory congestion not responding to medical therapy.
Acute Kidney Injury Timeline
Cardiorenal Interaction: The Future We need to use meaningful definitions and validate them in different clinical settings. We need to evaluate the impact of early biomarkers on diagnosis and various therapeutic approaches We need to appraise current evidence and generate wise recommendations for practice. We need research to generate the missing evidence.