The Electrical System Of The Sweet Heart
Atrial Fibrillation In Diabetics : A Turning Point In Life Expectancy. The Electrical System Of The Sweet Heart. G.L. Botto, MD, FACC, FESC U.O. Cardiologia U.O.Elettrofisiologia Ospedale Sant’Anna, Como. Remodeling. Ventricular dilation. MI. HF.
The Electrical System Of The Sweet Heart
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AtrialFibrillation In Diabetics: A Turning Point In Life Expectancy The Electrical System Of The Sweet Heart G.L. Botto, MD, FACC, FESC U.O. Cardiologia U.O.Elettrofisiologia Ospedale Sant’Anna, Como
Remodeling Ventricular dilation MI HF End-stage microvascular heart disease Atherosclerosis and LVH Risk factors (diabetes, hypertension) Death Atrial fibrillation AFIB Within The Cardiovascular Continuum AF is NOT a DISEASE, but rather a manifestation of a number of CLINICAL SYNDROMES, some of which are curable
CHS Multivariate Correlates of AF Prevalence Age (per 7-yr interval) * 1.03 (1.00–1.05) Gender(men vs women) 1.02 (0.77–1.35) 2.67 (1.57–4.55) CHF * Valvular heart disease * 3.27 (2.23–4.81) 1.57 (0.95–2.60) Stroke * 4.35 (1.42–13.35) Mitral stenosis * 1.62 (1.15–2.29) Aortic regurgitation * 2.69 (2.21–3.27) LA diameter * 1.39 (1.05–1.83) Hypertension * 0 4 8 12 16 * p < 0.05 ( ) 95% CI FurbergCD. Am J Cardiol 1994; 74: 236-241.
Development of a Risk Score for AF: A Community-BasedCohort (Framingham HS)HazardRegressionCoefficient for 10-Year Risk of AF Schnabel RB. Lancet 2009; 373: 739-45
Cumulative Exposure to DM and Risk of Prevalent AFA Casual Association ? Risk of newly AF by duration of treated DM Risk of newly AF by level of Hb A1c Dublin S. J GenInternMed 2010; 25: 853-8
Type 2 Diabetes Mellitus and Riskof Incident AF in Women the risk associated with T2DM is mainly mediated by changes of other AF RF Schoen T. J AmCollCardiol 2012; 60: 1421–8
Type-2 DiabetesMellitus and Risk of AFMeta-Analysis of Cohort and Case-Control Studies on 108.703 Cases • Studiesthathadadjustedfor multiple risk factors reported a smaller effect estimate compared to age-adjusted studies.(RR 1.24, 95% CI 1.06 to 1.44, vs1.70, 1.29 to 2.22). • The population attributable fraction of AF owing to T2DM was 2.5% (95% CI 0.1 to 3.9). Huxley RR. Am J Cardiol 2011; 108: 56-62
How IncreasedGlucoseLevels and DM MayExert a ProarrhythmicEffect ? • No evidence to indicate that T1DM isassociated with an increasedrisk of AF • Collier A. PostgradMed J 1987; 63: 895-897 • Insulinresistenceratherthanhyperglicemiaisresponsible for the increasedrisk of AF • Insulinresistenceisalso a mechanism by whichhypertension and obesityare associated with increasedrisk of AF • Yamagishi SI. HormMetab Res 2008; 40: 640-644 • Ostgren SJ. DiabetesObesMetab 2004; 6: 367-74 • DM and impairedglucosetolerance are associated with LVHwhichis a significantriskfactor for AF • Rutter MK. Circulation 2003; 107: 448-454 • Long-terminflammationmay be the mechmediating the link between DM and AF
CT Scan in an AFIB Patient With Ischemic Stroke in The Territory of the MCA AF increases of stroke risk 4-5 fold
Events Rate by StrokeRiskFactors, CHADS2 Score and Anticoagulation State in 11526 Adults With AF Go AS. JAMA. 2003; 290: 2685-2692
Human AF Substrate: Surgical Biopsies C Aimé-Sempé. J Am Coll Cardiol 1999;34:1577. SR Colagen (Mason’s tricrhomic) Elastic fibers (Orceine) AF
Neuroumoral Activation in AFIB HIGH ATRIAL PRESSURE OR VOLUME ATRIAL FIBROSIS ATRIAL REMODELING
Thiazolidinediones (Rosiglitazone)Agonists Of Peroxisome Proliferator Activated Receptor Gamma (PPAR-γ)Can Prevent New Onset AF In Pts With Non-insulinDependentDiabetes • TZDs have been proven to have - anti-inflammatoryand - anti-oxidant effects in addition to- anti-diabetic activity • 12,065 NIDDM pts from the “National Health Insurance Research Database” by the Taiwan National Health Research Institutes • 4137 ptswith TZD use were the study cohort and 7928 pts w/out TZD use were the comparison cohort -31% Chao TF, Chen SA, Int J Cardiol 2011; 156: 199-202
PPAR-γ Activator (Pioglitazone) as Upstream Therapy for Age-Related AF in Rats Xu D. J CardiovascElectrophysiol, 2012; 23: 209-217
Clinical Benefits Of TZDs On Atrial Fibrillation Prevention Home PD, et al. Rosiglitazoneevaluatedforcardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009;373:2125–35 Dormandy, et al. Secondarypreventionofmacrovascularevents in patients with type 2 diabetes in the proACTIVE study (prospectivepioglitazoneclinical trial in macrovascularevents): a randomisedcontrolled trialLancet 2005;366:1279–89 DeFronzo, et al. Pioglitazonefordiabetespreventionin impaired glucose tolerance (ACT-NOW) N Engl J Med 2011;364:1104–15
AtrialFibrillation in DiabeticsDM is associated with an increased risk of subsequent AF but … • The population-attributable fraction of AF owing to DM is very low • Studies that had adjusted for multiple RFs reported a smaller effect • The risk associated with T2DM is mainly mediated by changes of other AF RF • The mech that may underpin the relation between DM and AF remains speculative • Long-terminflammationmay be the mechmediating the link between DM and AF • Rooms for furtherupstreamRxin AF • AF in diabeticspatientsexerts an elevatedthromboembolicrisk