Ischemic Heart Failure

Transcription

1 Kalymnos Days Hellenic Cardiological Society Kalymnos, June 11, 2016 Ischemic Heart Failure Filippos Triposkiadis, MD, FESC, FACC Professor of Cardiology Director, Department of Cardiology Larissa University Hospital Larissa, Greece

2 Epidemiology Pathophysiology Treatment Viability Testing Conclusions

3 Epidemiology

4 Shepard D, et al. Circ Cardiovasc Qual Outcomes 2015;8:

5 Map of Age-Standardized Ischemic Heart Disease Mortality Rate per Persons Moran AE, et al. Circulation. 2014;129:

6 The Heart Failure Paradox: An Epidemic of Scientific Success Jessup M. Circulation. 2014;129: Terzic A, Behfar A. Trends Cardiovasc Med, 2016, in press

7 Characteristics of Hospitalized Patients with HF LVEF 50% (n=40,354) 40% LVEF<50% (n=15,184) LVEF<40% (n=55083) Age (years) 78 (67-85) 76 (65-84) 70 (58-80) Female sex (%) Body mass index>30 kg/m 2 (%) Anemia Hypertension Diabetes (oral therapy) Diabetes (insulin) Chronic/recurrent atrial fibrillation Coronary artery disease Pulmonary disease Chronic kidney disease Steinberg B, et al. Circulation 2012;126:65-75

8 Variable Odds ratios* (95% CI) P value Hypertension 9.43 (5.85, 15.17) < Myocardial infarction 0.06 (0.04, 0.09) < Obesity 3.24 (2.23, 4.69) < Diabetes 0.57 (0.37, 0.90) 0.01 *Higher odds for: i) HFpEF, if OR>1.0; ii) HFrEF, if OR<1.0 Determinants of the HF Phenotype Giamouzis G, et al. Heart Failure 2016, Florence

9 Survival Survival Definition of Ischemic Cardiomyopathy (?) (Ischemic HFrEF) for Use in Clinical Research The clinical history and coronary anatomy of pts with symptomatic HF and LVEF 40% undergoing diagnostic coronary angiography between 1986 and 1999 (n =1,921) was assessed. Five classification schemes were tested to develop the best definition of ischemic cardiomyopathy for prognostic purposes. Patients with 75% stenosis of the LMCA or proximal LAD were included in the ischemic group. Non ischemic 1 VD No significant CAD Ischemic 2 VD 3 VD Years Years Patients with single-vessel disease and no history of MI or revascularization should be classified as nonischemic for prognostic purposes. Felker GM, et al. J Am Coll Cardiol 2002;39:210 8

10 Ischemic Cardiomyopathy (Ischemic HFrEF): Independent Predictors of Survival in the Best Multivariable Model Felker GM, et al. J Am Coll Cardiol 2002;39:210 8

11 Operating Characteristics of Stress Testing in HFpEF Clinical, hemodynamic, echocardiographic, treatment, and outcome characteristics examined in consecutive patients with previous HFpEF (n=376) hospitalizations who underwent coronary angiography during an 8 year study. Hwang SJ, et al. J Am Coll Cardiol 2014;63:

12 Longitudinal Changes in LVEF in HFpEF Μedian interval of 1,314 days (IQR: 655 to 1,947 days) Hwang SJ, et al. J Am Coll Cardiol 2014; 63 :

13 Εffect of Coronary Artery Disease in HFpEF Survival Μedian follow-up of 1,457 days (IQR: 692 to 2,366 days) Hwang SJ, et al. J Am Coll Cardiol 2014;63:

14 Pathophysiology

15 Determinants of the Myocardial Blood Flow Gaemperli O, et al. European Heart Journal 2013; 34:

16 The Ischaemic Cascade Gaemperli O, et al. European Heart Journal 2013; 34:

17 Spectrum of Myocardial Dysfunction in Ischaemic Heart Failure Shah BN, et al. Eur Heart J 2013;34:

18 The Concept of Lethal Reperfusion Injury Ovize M, et al. Cardiovascular Research 2010; 87:

19 The No-Reflow Phenomenon Bouleti C, et al. Archives of Cardiovascular Disease 2015; 108:

20 Infarct Size as a Function of Duration of Ischemia and Residual/ Collateral Blood flow Heusch G. Compr Physiol 2015;5:

21 Relationship Between Baseline LVEF and Subsequent Change in LVESV and LVEDV Schächinger V, et al. Eur J Heart Fail 2009;11:973 9

22 Relationship Between Initial Infarct Size (% LV Mass) and Subsequent Change in LVEDV Index Wu E, et al. Heart 2008;94:730 6

23 Inflammation and Remodeling after AMI Westman PC, et al. J Am Coll Cardiol 2016;67:

24 Complex Cardiac ECM with Potential Functions of Some Residing Matrix Elements Healthy Myocardium Myocardial Infarction Rienks M, et al. Circ Res. 2014;114:

25 Left Ventricular Wall Stress, Geometry, and Remodeling in Myocardial Infarction D Elia N, et al. J Am Coll Cardiol Img 2015;8:

26 Pathophysiology of Functional Mitral Regurgitation D Elia N, et al. J Am Coll Cardiol Img 2015;8:

27 Treatment

28 Therapeutic Algorithm in Patients with Symptomatic HFrEF ESC Guidelines 2016

29 Enrolment and Outcomes in the STICH Hypothesis 1 and Hypothesis 2 Trials Jones RH, et al. N Engl J Med 2009;360:

30 The STICH Trial: CABG with or without SVR Between September 2002 and January 2006, 1000 patients with a LVEF 35% or less, coronary artery disease amenable to CABG, and dominant anterior LV dysfunction that was amenable to SVR were randomly assigned to undergo either CABG alone (n=499) or CABG with SVR (n=501 patients). The primary outcome was a composite of death from any cause and hospitalization for cardiac causes. The median follow-up was 48 months. Jones RH, et al. N Engl J Med 2009;360:

31 The STICH Trial: CABG in Patients with LV Systolic Dysfunction /Intermediate Outcomes Between July 2002 and May 2007, 1212 patients with LVEF 35% or less and CAD amenable to CABG randomly assigned to medical therapy alone (n=602) or medical therapy plus CABG (n=610). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of CV death and of death from any cause or hospitalization for CV causes. Median follow-up 56 months. Velazquez EZ, et al. N Engl J Med 2011;364:

32 The STICH Extension Study: CABG in Patients with LV Systolic Dysfunction /Long-Term Outcomes Outcomes The median duration of follow-up, including the current extended-followup study, was 9.8 years. Velazquez EZ, et al. N Engl J Med 2016;374:

33 Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation 301 patients randomly assigned to undergo either CABG alone or CABG plus mitral valve repair. Patients were followed for 2 years for clinical and echocardiographic outcomes. Michler RE, et al. N Engl J Med 2016;374:

34 Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation 251 patients randomly assigned to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed Goldstein D, et al. N Engl J Med 2016;374:344-53

35 Cumulative Failure of MV Repair or MV Replacement Goldstein D, et al. N Engl J Med 2016;374:344-53

36 Impact of Revascularization on Longitudinal Changes in LVEF in HFpEF Hwang SJ, et al. J Am Coll Cardiol 2014; 63 :

37 Impact of Revascularization on Survival in Patients With HFpEF With CAD Hwang SJ, et al. J Am Coll Cardiol 2014; 63 :

38 Viability Testing

39 Myocardial Viability Testing and Impact of Revascularization on Prognosis in CAD and LV Dysfunction: A Meta-Analysis 24 viability studies reporting patient survival using thallium perfusion imaging, F-18 fluorodeoxyglucose metabolic imaging or dobutamine echocardiography. There were 3,088 patients (2,228 men), LVEF 32±8%, followed for 25±10 months. Allman KC, et al. J Am Coll Cardiol 2002;39:1151 8

40 The STICH Trial: Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, 298 were randomly assigned to receive medical therapy plus CABG and 303 to receive medical therapy alone. The comparison shown not adjusted for other prognostic baseline variables. After adjustment on multivariable analysis, the between-group difference was not significant (P = 0.21). Bonow RO, et al. N Engl J Med 2011;364:

41 The STICH Trial: Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction Bonow RO, et al. N Engl J Med 2011;364:

42 The STICH Trial: Kaplan-Meier Analysis of Mortality Rates in Patients With Myocardial Viability Bonow RO, et al. J Am Coll Cardiol Img 2015;8:1121 9

43 The STICH Trial: Kaplan- Meier Analysis of Mortality Rates in Patients With Myocardial Viability in 3 Subgroups of ESVI Bonow RO, et al. J Am Coll Cardiol Img 2015;8:1121 9

44 The CHRISTMAS Trial: Myocardial Viability as Determinant of LVEF Response to Carvedilol in HF Double-blind, RT carvedilol vs. placebo for 6 months in individuals with stable, chronic HF due to ischaemic LV systolic dysfunction. 489 patients enrolled, of whom 387 were randomised. The primary endpoint was change in LVEF, measured by RNV, in hibernators vs. nonhibernators, on carvedilol compared with placebo. Analysis was by intention to treat. Cleland JGF, et al. Lancet 2003; 362: 14 21

45 Conclusions

46 CAD is a contributing factor in approximately 50% cases of HF and adversely affects survival. Ischemic HF is increasing in incidence due advancements in AMI management with overall improved survival. Stunned and hibernating (viable) myocardium together with myocardial necrosis and scar tissue contribute to the development of LV remodeling and ischemic HF. The results of the STICH Extension Study support a significant benefit of CABG plus medical therapy over medical therapy among patients with ischemic HF. Observational studies suggest that patients with viable myocardium may benefit after revascularization. However, RCTs dispute the value of viability testing. In ischemic HF with moderate MR, MV repair does not retard progression of LV remodelling or significantly improve survival or reduce overall adverse events or readmissions. In ischemic HF with severe MR, MV replacement provides more durable correction of MR, which, however, must be weighed against the consequences related to the prosthetic valve.

47

48

49

50

51 Pre-procedural factors Reasons viable myocardium may not recover function following revascularization Post-procedural factors Post-procedural factors Shah BN, et al. Eur Heart J 2013;34:

52 15 th Cardiology Congress of Northern Greece Thessaloniki, May 26-28, 2016 Ischemic Heart Failure Filippos Triposkiadis, MD, FESC, FACC Professor of Cardiology Director, Department of Cardiology Larissa University Hospital Larissa, Greece

53 Sustained VT Anchored to Compact Scar Ripplinger CM, et al. Heart Rhythm 2009; 6: 87 97

54 Critical Determinants of Myocardial Infarction Injury Montecucco F, et al. European Heart Journal 2016; 37:

55 The STICH Trial: Patients, Randomization, and Follow-up Between July 2002 and007, 1212 pts with an LVEF 35% and CAD amenable to CABG were randomly assigned to medical therapy alone (n=602) or medical therapy plus CABG (n=610). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from CV causes and of death from any cause or hospitalization for CV causes.

56 The STICH Trial: CABG in Patients with LV Systolic Dysfunction/Intermediate Subgroup Analyses of Death from Any Cause Velazquez EZ, et al. N Engl J Med 2011;364:

57

58 Infarct Size Reduction by Pre- and Postconditioning Zhao Z-Q, et al. Am J Physiol Heart Circ Physiol 2003;285:H579 H588

59 The STICH Trial: Extent of Viability and ESV Expressed as Continuous Variables Bonow RO, et al. J Am Coll Cardiol Img 2015;8:1121 9

60 The Conditioning Stimulus and the Impact of Co-Morbidity and Drug Therapies Bell RM, et al. Basic Res Cardiol 2016; 111:41

61 Anti-Inflammatory Therapy in Myocardial Infarction: Pre-Clinical Evidence Montecucco F, et al. European Heart Journal 2016; 37:

62 Reduction of Infarct Size Heusch G, et al Lancet 2014; 383(9932):

63 Apoptosis Predominates in Nonmyocytes in Heart Failure Park M, et al. Am J Physiol Heart Circ Physiol 297:H785 H791

64

65

66

67

68

69 The STICH Extension Study: CABG in Patients with LV Systolic Dysfunction/Long-Term Subgroup Analyses of Death from Any Cause Velazquez EZ, et al. N Engl J Med 2016;374:

70 Temporal Trends in Ischemic Heart Disease Mortality in 21 World Regions, 1980 to 2010 The Global Burden of Disease 2010 Study Males Females Moran AE, et al. Circulation. 2014;129:

71

72 A Novel Paradigm for HFpEF: Comorbidities Drive Myocardial Dysfunction and Remodeling Through Coronary Microvascular Endothelial Inflammation Hypertension Overweight/Obesity Diabetes Mellitus Kidney disease Iron deficiency COPD IL-6 TNF-α sst2 Pentraxin 3 Endothelium ONOO- ROS NO VCAM E-selectin TGF-β Leukocytes Fibroblasts Myofibroblasts sgc Collagen Cardiomyocytes cgmp Fpassive PKG Hypertrophy Paulus WJ, Tschoepe C. JACC 2013; 62:263-71

73 Myocardial Remodeling in HF R EF Endothelium Collagen Autophagy Apoptosis Necrosis Cardiomyocytes ROS Ischemia Infection Toxicity Paulus WJ, Tschoepe C. JACC 2013; 62:263-71

74 Ischaemic Conditioning Bell RM, et al. Basic Res Cardiol 2016; 111:41

75 Positive and Negative Arterial Remodelling Influences the Consequences of Atherosclerosis Heusch G, et al Lancet 2014; 383(9932):

76 Role of Microembolisation in Coronary Vascular Remodelling Heusch G, et al. Circulation 2009; 120:

77 Myocardial Remodelling in Response to Pressure Load Opie LH, et al. Lancet. 2006; 367:

78 The Metabolic Vicious Circle in Heart Failure Opie LH. Lancet. 2004; 364:

79 The Concept of Lethal Reperfusion Injury Ovize M, et al. Cardiovascular Research 2010; 87:

80 The STICH Trial: Severity of Remodeling, Myocardial Viability, and Survival Interactions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 9 years; ejection fraction #35%), with a median follow-up of 5.1 years. Bonow RO, et al. J Am Coll Cardiol Img 2015;8:1121 9

81 Optimal Healing Post Myocardial Infarction Francis Stuart SD, et al. Journal of Molecular and Cellular Cardiology 2016; 91:

82

83

84

85 Prognostic Significance of Biomarkers in Patients With CAD and LV Dysfunction: STICH HYPOTHESIS 1 Feldman AM, et al. Circ Heart Fail 2013;6:

86 Biphasic Monocyte Response During Early Myocardial Remodeling Swirski FK, Nahrendorf M. Science 2013 ; 339(6116):

87 Prognostic Significance of Biomarkers in Patients With CAD and LV Dysfunction: STICH HYPOTHESIS 2 Feldman AM, et al. Circ Heart Fail 2013;6:

88 Prediction of Functional Recovery Post-Revascularization Kaandorp TA, et al. Heart 2005;91:

89 Ischemic Heart Disease Shepard D, et al. Circ Cardiovasc Qual Outcomes 2015;8:

90 Heart Failure Etiology Gheorghiade M, et al. Circulation 2006;114:

91 Ischaemia/Reperfusion Injury and the Different Forms of Cell Death Bell RM, et al. Basic Res Cardiol 2016; 111:41

92