There is no conflict of interests for the following presentation

Transcription

1 There is no conflict of interests for the following presentation

2 Inflammation and Left Ventricular Diastolic Dysfunction Cho-Kai Wu MD National Taiwan University Hospital, Taipei, Taiwan

3 Diastolic heart failure 1. At least 1/3 ~1/2 of all patient with CHF have a normal or near-normal ejection fraction 2. LV diastolic dysfunction independent prognostic marker for the mortality of critically ill patients with preserved EF and for healthy population NEJM 2004, 351: Shock 2010; 33: 141-8

4 Introduction DHF is a Multifactorial Disease Age Race Gender Obesity Cytokines activation SNS activation Diabetes Mellitus Genetic factors Hypertension Arterial stiffness Volume load Hyperlipidemia Pericardial Endocardial

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6 Cytokines decrease SERCA mrna amount J Mol Cell Cardiol 28, (1996)

7 Hypothesis Inflammatory Cytokines Changes of SERCA2 levels LV diastolic dysfunction or even DHF Especially in specific patients with high inflammation!!!

8 SERCA2 Luciferase expression in cardiomyocytes after cytokines

9 SERCA 2 Real-time PCR results

10 SERCA2 Western Blot

11 Calcium Current Changes Functional changes

12 Inflammation and DHF Clinical Studies

13 Methods Group 1 Clinical Variables Age (difference<5 yrs) Gender Enrolled Exclusion Study Subjects criteria (Exclusion Significant Criteria/Clinical CAD Variables) from Taiwanese Population Significant valvular heart disease Hypertension Smoking YES Diastolic dysfunction: Congenital heart diseases E/Em >15 or 8<E/Em 15 E/A<0.7 and E deceleration time >280 cm/s Systolic BP (difference <10 mmhg) Heart transplantation Diastolic BP (difference <10 mmhg) Variants of cardiomyopathies Anti-Hypertensive therapy NO Active Infection or 32 Cases Inflammation 70 Controls Inflammatory Cytokines levels Overt hyperthyroidism HOMA, Lipids Devereux RB Am J Cardiol 57: , 1986 Pericardial disease J Am Coll Cardiol 7: , 1986 All patients received Abdominal CT

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18 Methods CAPD patients Enrolled Clinical Exclusion Study Variables Subjects criteria (Exclusion Significant Criteria/Clinical CAD Variables) from Taiwanese Population Significant valvular heart disease Age (difference<5 yrs) Gender Hypertension Smoking Diastolic dysfunction: E/Em >15 or 8<E/Em 15 E/A<0.7 and E deceleration time >280 cm/s Congenital heart diseases Systolic Heart BP (difference transplantation <10 mmhg) Diastolic Variants BP (difference of cardiomyopathies <10 mmhg) Anti-Hypertensive therapy Active Infection or 101 CAPD Inflammation 120 controls Inflammatory Cytokines levels Overt hyperthyroidism Lipids, Glucose Devereux RB Am J Cardiol 57: , 1986 Pericardial disease J Am Coll Cardiol 7: , 1986 Chronic lung disease

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22 Conclusion Inflammatory Cytokines SERCA2 decreased Calcium current changes LV diastolic dysfunction Inhibition of inflammatory cytokines (ex: Obesity, PD patients Higher inflammatory cytokines levels with statin) May reverse the process Cytokines changes parallel Cardiac diastolic dysfunction parameters and improve outcomes in specific group Addition interaction between inflammation with specific group for LVDD

23 Acknowledgments and Our Study Group Chia-Ti Tsai, MD Chuen-Den Tsen, MD Juey-Jen Hwang, MD Jen-Kuang Lee, MD Jiunn-Lee Lin, MD Ling-Ping Lai, MD Kwan-Lih Hsu, MD Yung-Zu Tseng, MD Fu-Tien Chiang, MD National Taiwan University Hospital, Taiwan Thanks for Your Attention

24 Am J Physiol Heart Cir Physiol 2007; 202:H

25 J Mol Cell Cardiol 1999; 31:

26 Am J Physiol Heart Circ Physiol 2003; 286: H Circ Res 1994; 75:

27 SERCA 2 Real-time PCR results for different doses

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