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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.

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the electrical system of the sweet heart

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

slide2

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
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.

slide4
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 af a casual association
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 risk of incident af in women
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

slide7
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 increased glucose levels and dm may exert a proarrhythmic effect
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
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 stroke risk factors chads 2 score and anticoagulation state in 11526 adults with af
Events Rate by StrokeRiskFactors, CHADS2 Score and Anticoagulation State in 11526 Adults With AF

Go AS. JAMA. 2003; 290: 2685-2692

c aim semp j am coll cardiol 1999 34 1577

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
Neuroumoral Activation in AFIB

HIGH ATRIAL PRESSURE OR VOLUME

ATRIAL FIBROSIS

ATRIAL REMODELING

slide15

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 activator pioglitazone as upstream therapy for age related af in rats
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
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

atrial fibrillation in diabetics dm is associated with an increased risk of subsequent af but
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