Pathophysiology and Diagnosis of Heart Failure

Transcription

1 Pathophysiology and Diagnosis of Heart Failure Francesco Paneni, MD, PhD, FESC Cardiology Unit Karolinska University Hospital Stockholm, Sweden Cardiology University Hospital Zurich Switzerland

2 Disclosures: None

3 Case Vignette A 58-year-old man with no previous medical history presents with 3 months of progressive dyspnea on exertion and mild lower-extremity edema. Initial evaluation: FPG 167 mg/dl HbA 1c 7.8% Triglycerides 210 mg/dl HDL 30 mg/dl BP 135/80 mmhg Echocardiogram: moderate LV hypertrophy, ejection fraction 52%, pseudonormal diastolic filling (grade II DD), dilated inferior vena cava Coronary angiography: Non critical disease of LAD and RCA

4 Case Vignette Diagnosis T2D ATHEROGENIC DISLIPIDEMIA DIASTOLIC HEART FAILURE

5 Prevalence of HF in T2D Modified from Thrainsdottir IS, Aspelund T, Thorgeirsson G, et al. The association between glucose abnormalities and heart failure in the population-based Reykjavik study, Diabetes Care 28: , 2005.)

6 Glycemic status and HF No CHD CHD The ARIC study, Diabetologia 51: , 2008.

7 Prognosis of HF in T2D Diabetes in heart failure: prevalence and impact on outcome in the population, Am J Med 119: , 2006

8 Diabetic Cardiomyopathy Ventricular dysfunction that occurs independently of coronary artery disease and hypertension The postmortem findings and clinical records of 27 patients

9 Diabetic Cardiomyopathy Pathology The autopsy findings consisted of left ventricular hypertrophy and, in 1 case, right ventricular hypertrophy as well, in the absence of major coronary artery disease. Histopathologic study revealed diffuse fibrotic strands extending between bundles of muscle fibers and myofibrillar hypertrophy. In 1 case, the small intramural coronary arterioles demonstrated thickening of the wall and narrowing of the lumen due primarily to the deposition of acid mucopolysaccharide material in the subendothelial layers and subsequent subintimal thickening and medial hypertrophy. Rubler et al. Am J Cardiol. 1972;30:

10 Diabetic Cardiomyopathy Pathology Perivascular Fibrosis Cardiac Fibrosis

11 Sciarretta, Paneni et al. Clin Sci (Lond). 2009;116:467-77

12 Diabetic Cardiomyopathy Fang et al. Endocr Rev 25: , 2004

13 Diabetic Cardiomyopathy Fang et al. Endocr Rev 25: , 2004

14 IR/T2D Diabetic Cardiomyopathy Metabolic Changes INSULIN FFAs FAT Glucose GLUT-4 CARDIOMYOCYTE Paneni F, Cosentino F. Diabetes and Cardiovascular Disease: A Guide to Clinical Management Springer

15 Diabetic Cardiomyopathy Lipotoxicity and glucotoxocity INSULIN RESISTANCE K-ATP SERCA OXIDATION ROS NADPH p66 Shc PPARα PARP GAPDH AGEs

16 Diabetic Cardiomyopathy Molecular Mechanisms Advanced Glycation End Products (AGEs) Fraser D.A., Hanssen K.F. (2005). Making sense of advanced glycation endproducts and their relevance to diabetic complications. International Diabetes monitor. 17(3):1-7.

17 Diabetic Cardiomyopathy Molecular Mechanisms Heart Failure: A Companion to Braunwald s Heart Disease. 2nd edition

18 Diabetic Cardiomyopathy Lipotoxicity and glucotoxocity LIPOTOXICITY FFA oxidation Oxidative stress Ceramides generation Mitochondrial dysfunction Apoptosis K-ATP GLUCOTOXICITY Mito ROS accumulation PARP/GAPDH Apoptosis PKC activation AGEs SERCA

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20 Diabetic Cardiomyopathy: Hallmark Features Boudina S, Abel ED: Diabetic cardiomyopathy revisited, Circulation 115: , 2007

21 T2D Heart Failure in T2D Pathophysiology Phase I Phase II Ouzounian et al. Nat Clin Pract Cardiovasc Med 2008;5:375-86

22 Heart Failure in T2D Pathophysiology Heart Failure: A Companion to Braunwald s Heart Disease. 2nd edition

23 Diastolic Heart Failure Owan et al. N Engl J Med 2006; 355:251-9

24 Prognosis of Patients with Preserved and Reduced Ejection Fraction Owan et al. N Engl J Med. 2006; 355:251-9

25 Heart Disease in T2D Diagnosis Global CV risk Signs Symptoms Structural abnormalities Functional abnormalities

26 Heart Disease in T2D Diagnosis 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013; 128: e240-e327

27 Heart Disease in T2D Diagnosis The Health ABC Heart Failure score. Circ Heart Fail 2008;1: )

28 Heart Failure in T2D Diagnosis Pimobendan Multicenter Research Group. Am Heart J, 1992;124(4):

29 Diastolic Heart Failure Diagnosis 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013; 128: e240-e327

30 Heart Disease in T2D Diagnosis ECG Rhythm abnormalities Conduction abnormalities LA enlargement LVH Repolarization changes Prior MI? v1

31 Heart Disease in T2D Diagnosis Echocardiography Chamber dilation LVH LV geometry (RWT) Diastolic function LA volume Ejection Fraction Valvular disease IVC Ischemia

32 Diastolic Dysfunction Diagnosis RAPID FILLING ATRIAL CONTRACTION

33 Diastolic Dysfunction Diagnosis >1 < >2

34 Diastolic Dysfunction Diagnosis DIASTOLIC DYSFUNCTION LVH/Fibrosis

35 Diastolic dysfunction and HF Modified from From AM, Scott CG, Chen HH: The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction: a population-based study, J Am Coll Cardiol 55: , 2010

36 Heart Disease in T2D Diagnosis Cardiac MRI Circulation. 2008;118(10):

37 Heart Disease in T2D Biomarkers RAAS NPs ADM ST2 MMPs 3-NT oxldl Troponin Caspase-3 CRP AGEs IL-6 UACR Cys C NGAL

38 Heart Failure in T2D Biomarkers NT-proBNP Maisel et al. N Engl J Med 2002;347:

39 Heart Disease in T2D Biomarkers NT-proBNP In ambulatory patients with dyspnea, measurement of BNP or N- terminal pro-b-type natriuretic peptide (NT-proBNP) is useful to support clinical decision making regarding the diagnosis of HF, especially in the setting of clinical uncertainty. Measurement of BNP or NT-proBNP is useful for establishing prognosis or disease severity in chronic HF ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013; 128: e240-e327

40 Take Home Message Patients with T2D are at high risk of developing HF FFAs oxidation and hyperglycemia and are the main drivers of myocardial damage in DM Diastolic dysfunction, LVH and increased atrial volume are common features of diabetic cardiomypathy Assess global CV risk Structural heart disease must be ruled out in T2D patients (clinical exam, biomarkers, diagnostic tests)

41 Thank You