Hemodynamic improvement upon levosimendan treatment in low cardiac output patients following coronary artery bypass graft

Transcription

1 Hemodynamic improvement upon levosimendan treatment in low cardiac output patients following coronary artery bypass graft M. Buerke, K. Krohe, M. Russ, C. Schneider, H. Lemm, R. Prondzinsky, I. Friedrich, H. Bushnaq, R. Silber, K. Werdan Department of Medicine III & Department of Cardio-Thoracic Surgery Martin Luther-University Halle/Saale, Germany

2 Disclosure statement of financial interest The authors DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3 Symptoms Low cardiac output syndrome Clinical parameters Cardiac dysfunction Hypotension CI < 2,2 l/min/m² RRsys< 80 mmhg Increased afterload SVR > 1000 dynseccm 5 Tachycardia Oliguria HR > 100 /min < 0,5 ml/kg/h Acidosis ph < 7,35 Centralisation Dyspnea NYHA IV, cyanosis, cold limbs Female gender, age > 70 years, diabetes mellitus, 3-V-CAD, emergency or re-do surgery, STEMI (Rao et al.) Pulmonary & arterial Hypertension (Cortrufo et al.) Aortic clamp time (Kawamura et al.) Preexisting impaired renal function (Maganti et al.)

4 Vicious cycle of low cardiac output syndrome Myocardial Dysfunction Systolic Diastolic Cardiac Output Stroke Volume LVEDP Pulmonary Congestion Systemic Perfusion Hypotension Compensatory vasoconstriction Fluid Retention Coronary Perfusion pressure ISCHEMIA Hypoxemia Progressive myocardial Dysfunction DEATH

5 Outcome of low cardiac output syndrome Predictors of Low Cardiac Output Syndrome After Isolated Aortic Valve Surgery Prevalence of LCOS: 3.9% Mortality: 38% Maganti et al. 2004

6 Levosimendan Sensitizes cardiac troponin C towards Ca 2+ Improves Ca 2+ -dependent reconfiguration of the troponin complex leading to increased actin-myosin-crosslinks resulting in higher myocardial contractility

7 Levosimendan earlier studies Follath et al (LIDO-Studie) hemodynamic improvement (CI +30%, PCWP -20% after 24h) (Levo: 28%, Dobutamin: 15%) Mortality after 30 and 180 days (Levo: 7,8%, Dobutamin: 17%) Christoph,..., Buerke et al Levosimendan vs. IABP in cardiogenic shock Ruß,..., Buerke et al Hemodynamic improvement following levosimendan treatment in patients with acute myocardial infarction and cardiogenic shock Ruß,..., Buerke et al Right ventricular function in myocardial infarction complicated by cardiogenic shock: improvement with levosimendan

8 Levosimendan clinical use Treatment option for acute heart failure 1. Increased inotropy without proarrhythmogenic effects, effects on repolarisation, increase of oxygen consumption. 2. Decrease afterload by vasodilation due to ATPdependent K + -channel activation 3. Anti-Stunning-Effects Hepatic metabolism, T 1/2 ~1h, T 1/2 of metabolisms ~72h

9 Study design CABG LCOS Levosimendan epinephrine, norepinephrine, dobutamine -24h 0 3h 24h 48h 72h 96h N=41, March 2006 to February 2009

10 Patient characteristics Gender, (male / female) 29 (70,7%) / 12 (29,3%) Age, years, mean (range) 57.5 (24-73) BMI, mean (range) Kg/m ( ) Hypertension, n (%) 21 (51.2) Dyslipidemia, n (%) 17 (41.4) Diabetes mellitus, n (%) 14 (34.1) Previous AMI, n (%) 11 (26.8) Known heart failure, n (%) 29 (70.7) Cardiac risk factors (n=4), n/patient 1.4 Prior STEMI n (%) 7 (17.1) 1-vessel diseasen (%) 2-vessel diseasen (%) 3-vessel disease n (%) 5/41 (12,1%) 9/41 (22,0%) 15/41 (36,6%) Ejection fraction (echocardiography) 30,98±16,03 Prior Dialysis/acute renal failure, n 10/41 (24,4%) (%) APACHE score TP ±5,97 IABP before, during and after CABG 7 (17.1 %), 1 (2,4 %), 0 (0 %)

11 Patient characteristics number % EF reduced (<30%) 30 73,17 EF moderate reduced (<50%;>30%) 5 12,19 EF normal(>50%) 6 14,63 surgery 24 58,54 Re do surgery 15 36,59 survivial 23 56,1

12 min ¹ Overall effects HR & BP mmhg 100 Herzfrequenz Heart rate 120 Blutdruck Blood pressure RRsys RRdia MAP 82 Levo 0 Levo

13 L/min/m² dynscm⁵ Overall effects CI & SVR,PVR Cardiac index Index Systemic / pulmonary resistance Systemic / pulmonary resistance 3, ,50 2, , , SVR PVR 0, ,00 0

14 mmhg W/m² Overall effects PAM,RAP,PCWP & CPI 35 PAM RAP PCWP PAM RAP PCWP 0,60 Cardiac power index Cardiac Power Index ,50 0, , , PAM ZVD PCWP 0,10 0,00 CPI RVCPI

15 mmhg W/m² Outcome effects MAP & CPI Mean arterial pressure MAP Cardiac Power Index Cardiac power index 100 0, ,5 0,4 0, , Verstorben Non-Survivors Überlebt Survivors 0,1 0 Verstorben Non-Survivors Überlebt Survivors

16 min ¹ mmhg Gender effects HR & MAP Hart rate Heart rate MAP Mean arterial pressure Frauen Females Männer Males

17 L/min/m² dynscm ⁵ Gender effects CI & PVR CI Cardiac index PVR Pulmonary vascular resistance , , ,5 0 CI_F Females CI_M Males 50 0 Females PVR_F Males PVR_M

18 mmhg ml/min 120 Adverse effects of levosimendan Known adverse effects: Hypotension Bleeding Impaired renal function Blood pressure 66 Creatinine clearance creatinine clearance RRsys RRdia MAP

19 Conclusions In patients with low cardiac output syndrome.. -..Levosimendan improves hemodynamic effects. -..Levosimendan has beneficial effects on left and right ventricular failure. -..Levosimendan treatment did not result in profound hypotension, worsening of renal function or increased bleeding. Levosimendan is an useful option to treat patients with low cardiac output syndrome after coronary artery bypass surgery.

20 Thank you for your attention