Cardiorenal Syndrome

Transcription

1 SOCIEDAD ARGENTINA DE CARDIOLOGIA Cardiorenal Syndrome Joint session ESC-SAC ESC Congress 2012, Munich César A. Belziti Hospital Italiano de Buenos Aires I have no conflicts of interest to declare

2 Cardiorenal Syndrome Definition Prevalence Pathophisiology Clasification Prognosis New markers Therapeutic strategies

3 CRS - definition- State in which therapy to relieve the heart failure (HF) symptoms is limited by further worsening renal function (NIHLB, 2004) State in which each dysfunctional organ has the ability to initiate and perpetuate disease in the other organ through common hemodynamic, neurohormonal, and immunological / biochemical feedback pathways

4 Prevalence of renal dysfunction in HF Creatinine >2 mg/dl Creatinine > 3 mg/dl Renal substitution % ADHERE Registry : 274 hospitals in USA. N: 105, 388 ADHF

5 GFR in 200 patients with ADHF. Hospital Italiano de Buenos Aires GFR GFR GFR GFR (ml/min/1.73 m 2 ) (>90) (90-60) (<60) N (%) 36 (18%) 54 (27%) 110 (55%) Creatinine (mean : 1.57± 0.6 mg/dl ) GFR MDRD (mean: 59.5±17 ml/min/1.73 m2 ) Worsening renal function in patients admitted with acute decompensated heart failure: Incidence, Predictors and prognostic value. C. Belziti et al. HFSA, Toronto, Canada, 2008

6 CRS- Pathophisiology Low cardiac output Sympathetic overactivity RAAS overactivity Oxidative injury / inflammation / endothelial dysfunction Intraabdominal and central venous pressure elevation

7 HF Low cardiac output Arterial underfilling Sympathetic Nervous System RAAS non osmotic release ADH Lower renal perfusion Lower GFR H 2 O and Na retention

8 CRS- Pathophisiology Low cardiac output Sympathetic overactivity RAAS overactivity Oxidative injury / inflammation / endothelial dysfunction Intraabdominal and central venous pressure elevation

9 C R S: Oxidative injury / inflammation/ endothelial dysfunction RAAS NO / ROS Inflammation SNS RAAS NADH oxidase NO / ROS Cell Adhesion Molecules Inflammation AT- II SNS NO: Nitric oxide ROS: Reactive oxygen species SNS: Sympathetic Nervous System RASS: Renin-Angiotensin-Aldosterone System Adapted from L G Bongartz, M J Cramer, P A Doevendans et al. Eur Heart J, 2004

10 Changes in serum Creatinine mg/dl GFR (ml/min/1.73 m2 Number of patients Central Venous Pressure (CVP), Intra-Abdominal Pressure (IAP) and renal function Relationship between IAP and changes in seric creatinine Distribution of CVP and the relationship between CVP and GFR in 2557 patients Changes in IAP (mmhg) CVP mmhg Mullens et al. Damman et al

11 CRS - Clasification- Cardio-renal 1. Acute 2. Chronic Renal-cardiac 3. Acute 4. Chronic 5. Systemic disease Adapted from Ronco et al.

12 -Prognosis- HF: Mortality in patients with mild renal failure HR: 1.56 ( ) Cr >1.0 / GFR<90 - >53= GFR >90 ml= G L Smith et al.jacc 2006; 47:

13 Prognosis- HF: Mortality in patients with moderate/severe renal failure HR: 2.31 ( ) Cr >1.5 / GFR<53= GFR > 90 ml= G L Smith et al.jacc 2006; 47:

14 Incremental Mortality Risk per 10 ml/min GFR HR: 1.07 ( ) per 1 mg/dl Creatinine HR: 1.33 ( ) HR (IC 95%) G L Smith et al.jacc 2006; 47:

15 CHARM N=2680 p en USA (Added, Alternative, Preserved) H Hillege, D Nitsch, M. Pfeffer al Circulation Feb 7;113(5): a) EF < 40 % CV Mortality / HF Hospitalisation b) EF 40 % GFR by MDRD equation (ml/min / 1.73 m2)

16 ADHF & Worsening renal function 1.0 Kaplan- Meier curve of HF rehospitalisation free survival. % P< N= 200 pts. Without WRF With WRF (23%) WRF: Cr 0.3 mg/dl and GFR 25% m WRF (worsening renal function) Belziti CA et al. Worsening renal function in patients admitted with acute decompensated heart failure: Incidence, predictors and prognostic value. Rev Esp Cardiol. 2010; 63(3):

17 ADHF & Worsening renal function 1.0 Survival % P = 0, HF rehospitalisations Without WRF With WRF % P = 0, months meses without WRF With WRF meses months Belziti CA et al. Worsening renal function in patients admitted with acute decompensated heart failure: Incidence, predictors and prognostic value. Rev Esp Cardiol. 2010; 63(3):

18 Multivariate Analysis AGE: >80 años GFR: <60 ml/min/1.73 m 2 SBP: < 90 mmhg. WRF >>Mortality / HF rehospitalitations Belziti CA et al. Worsening renal function in patients admitted with acute decompensated heart failure: Incidence, predictors and prognostic value. Rev Esp Cardiol. 2010; 63(3):

19 New biomarkers of renal dysfunction / injury BUN Creatinine GFR (MDRD) Albumin (UAE) renal dysfunction: Cystatin-C tubular injury: NGAL, KIM-1, NAG

20 Seric Cystatin-C CYS-C No active tubular secretion No extrarenal elimination No re-entering to bloodstream CYS-C level is not affected by : Age Gender BMI Diet

21 Prognostic value of seric CYS-C in AHF (460 p.) 87.4% 59.6% normal Creatinine - normal CYS-C normal Creatinine - increased CYS-C (>mediana) Lassus J et al. Prognostic value of cystatin C in acute heart failure in relation to other markers of renal function and NT-proBNP. European Heart Journal 2007;28:1841-7

22 One year survival by tertiles of seric CYS-C 9.9% 24.8% 44.8% First tertile: <1.13 mg/dl Second tertile: Third tertile: >1.55 Lassus J et al. European Heart Journal 2007

23 Risk stratification combining tertiles of CYS-C and NT pro-bnp Mortality Lassus J et al. European Heart Journal 2007

24 Biomarkers of tubular damage in CHF CHF N= 90 Controls N=20) * p < vs controls Damman et al. Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart 2010; 96: 1297e 1302.

25 Risk of HF rehospitalisations / death

26 Therapeutic strategies Avoid harm during treatment (diuretics, nephrotoxic drugs) Early detection of renal dysfunction (new markers) Renal-preserving treatments (future)

27 Drugs Urine flow Mortality Natriuretic peptides Nesiritide + No change Isotonic fluid removal Ultrafiltration + Vasopresin receptor antagonist Tolvaptan + Adenosine receptor blocker Rolofilline + Inotropes Levosimendan + Devices << sympathetic drive?? Intrarenal delivery of drugs??

28 SOCIEDAD ARGENTINA DE CARDIOLOGIA Thank you for your attention!! César A. Belziti Hospital Italiano de Buenos Aires