Ventricular Interactions in the Normal and Failing Heart

Transcription

1 Ventricular Interactions in the Normal and Failing Heart Congenital Cardiac Anesthesia Society 2015

2 Pressure-volume relations Matched Left ventricle to low hydraulic impedance Maximal stroke work limited Ventricular volumes and ejection fraction sensitive to acute changes in afterload Afterload Volume sensitivity x4-5 of LV Right ventricle Volume Redington et al. Br Heart J 1989

3 Afterload Sensitivity MacNee W. Am J Respir Crit Care Med. 1994;150:

4 Shared fibres Series Parallel Geometric Co-ordination -Functional Acute Chronic Systole Diastole -Electrical Sanchez-Quintana et al. Heart 1999

5 PHT: A BIVENTRICULAR DISEASE? Myocardial crosstalk Damiano et al. Am J Physiol 1991

6 Aortic constriction leads to increased RV stroke volume and developed pressure during experimental PA constriction Yamashita et al. Jpn Circ J 1989 Belinkie et al. Circulation 1995 Apitz C et al. Thoracic & Cardiovasc Surg 2011

7 Acute RV failure 250 PA FLOW P=0.04 PA FLOW mls.min P=ns PA Band +Ao Band +NorEpi Apitz et al. J Thorac Surg 2011

8 Acute RV failure RV ESPVR RV ESPVR (mmhg.ml -1 ) P<0.002 Isolated acute RV systolic failure: Post bypass (e.g.ebsteins) Post transplant RV infarction PA Band +Ao Band +NorEpi Apitz et al. J Thorac Surg 2011

9 10 Infants, 2 toddlers Mean age 263 days 2 late deaths both LVNC J Heart Lung Transplant May;32(5):475-81

10 Acute RV failure RV ESPVR Pressure (mmhg) PVLoop Volume (mls) Apitz et al. Submitted 2010

11 RV afterload: Acute effects Contractility

12 RV afterload: Chronic effects Pressure Volume Redington et al. Br Heart J 1988:58:23-8

13 Chronic PHT RIGHT VENTRICLE Compensated adaptation, no RV failure Gaynor et al. Circulation 2005; 112:212-18

14 Chronic effects Pressure Volume

15 Physiology Symptomatic deterioration when PVR > SVR

16 Diastolic interaction? Raymond et al. JACC 2002; 39:1214-9

17 Physiology

18 Physiology

19 Diastolic interaction? Tricuspid valve Mitral inflow Increased duration of RV systole leads to reduced LV preload

20 Ventricular interaction Gan et al. Am J Physiol 2006; 290:

21 Ventricular interaction Gan et al. Am J Physiol 2006; 290:

22 Ventricular interaction (Systole-Diastole) Cardiac Output ~ Heart Rate Beware Tachycardia Rate control Gan et al. Am J Physiol 2006; 290: as a therapy?

23 Ventricular interaction Alkon, Humpl, Friedberg. Am J Cardiol 2011

24 Other therapeutic options? Reduce RV preload -Atrial Septal Defect Increase RV inotropy Reduce RV afterload Modify myocardial responses

25 Decreased RV afterload Pressure Volume

26 Chronic effects Pressure RV AFTERLOAD = SVR Volume

27 Outcomes Better survival despite higher PVR From Hopkins WE. Cor Art Dis 2005; 16:19-25

28 Outcomes Potts anastomosis (LPA to descending Aorta) 7 children (3 with TGA) All suprasystemic PAH (PVR WU.M 2 ) 1 perioperative death, F/U 22 months SaO vs 80+9% Improved NYHA, 6 MW, medical Rx Serraf et al ATS 2007

29 Serraf et al ATS 2007

30 N=8 Ann Thorac Surg 2012;94:817 24

31 Right-left heart interaction Hoffman et al. JTCVS 1994; 107:

32 Acute RV dilation 40 adult pigs Acute RV ischaemia LV and RV conductance catheter Brooks et al. Circulation 1999;100:761-7

33 Acute RV dilation Pericardium Closed Pericardium Open Brooks et al. Circulation 1999;100:761-7

34 Change in Cardiac Output Cardiac output (l/min ) 0-1 p = Pericardium Intact Pericardium Open

35 Parallel Interaction: ToF TOF - IVC Occlusion 100 ESPVR = 0.54 mmhg / ml Pressure (mmhg) EDPVR = 0.06 mmhg / ml Volume (x10-1 ml) AHA 2003

36 Parallel Interaction: ToF 100 TOF - IVC Occlusion ESPVR = 0.54 mmhg / ml TOF - PA Occlusion ESPVR = 0.35 mmhg / ml Pressure (mmhg) EDPVR = 0.06 mmhg / ml EDPVR = 0.19 mmhg / ml Volume (x10-1 ml) AHA 2003

37 Chronic parallel interaction?: ToF Davlouros et al JACC 2002 Ghai et al JACC 2002

38 Parallel interaction: ToF LEFT VENTRICULAR EJECTION LVEF pre-post PVR BEFORE AND AFTER PVR LV diastolic dysfunction? pre PVR post PVR Tobler et al. Am J Cardiol 2010

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40 T1 mapping: Tetralogy of Fallot Table 2. Post-contrast T1 values of patients and controls. IVS = interventricular septum; LV = left ventricle; RV = right ventricle Segment Patients (n = 18) Controls (n = 12) p IVS 438 ± 52 ms 467 ± 85 ms 0.27 LV lateral wall 443 ± 54 ms 510 ± 77 ms 0.01 RV inferior wall 394 ± 64 ms 429 ± 69 ms 0.25 RV anterior wall 333 ± 62 ms 392 ± 73 ms 0.04 Kozak,,Grosse-Wortmann. Ped Radiol 2014

41 Parallel interaction: signaling Chronic Banding Apitz et al. JTCVS 2012

42 Myocardial responses Methods AO+PAB PAB Groups: New Zealand kg AO+PAB PAB PAB PAB+AO n=9 n=9 RNA Extraction Real-time PCR Collect Heart Tissue Embed Tissue Histological Staining *only RV Image Analysis ET-1 ENDRA ENDRB MMP2 MMP9 TGF CTGF MT SR H&E Mild Ao banding ( LVP ~10mmHg reduces RV fibrosis Apitz JTCVS 2012

43 Myocardial responses Trichrom RV fibrosis (trichrom) ANOVA p=0.01 Picorius Red staining RV collagen (PSR) ANOVA p< Sham PA band Ao band PA + Ao band Losartan 0 Sham PA band Ao band PA + Ao band Losartan Friedberg M et al. Am J Respir Cell Mol Biol. 2013

44 Myocardial responses LV fibrosis (trichrom) 4 ANOVA p= Picorius Red staining LV collagen (PSR) ANOVA p< Sham PA band Ao band PA + Ao band Losartan 0 Sham PA band Ao band PA + Ao band Losartan Friedberg M et al. Am J Respir Cell Mol Biol. 2013

45 Conclusions Shared myocardium and pericardium imposes ventricular interaction Beneficial interactions may be harnessed RV dilation impairs biv systolic and diastolic function Improved understanding will lead to improved care and novel therapies