The Electrical System Of The Sweet Heart

G.L. Botto, MD, FACC, FESCU.O. Cardiologia

U.O.Elettrofisiologia Ospedale Sant’Anna, Como

Atrial Fibrillation In Diabetics:

A Turning Point In Life Expectancy

AFIB Within The Cardiovascular ContinuumAFIB Within The Cardiovascular Continuum

Risk factors(diabetes,

hypertension)Atrial fibrillation

MI

Atherosclerosis and LVH

Remodeling Ventriculardilation

HF

End-stage microvascular heart disease

Death

AF is NOT a DISEASE, but rather a manifestation of a number

of CLINICAL SYNDROMES, some of which are curable

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

0 16

Furberg CD. Am J Cardiol 1994; 74: 236-241.

4 8 12

1.03 (1.00–1.05)1.03 (1.00–1.05)

1.02 (0.77–1.35)1.02 (0.77–1.35)

2.67 (1.57– 4.55)2.67 (1.57– 4.55)

3.27 (2.23–4.81)3.27 (2.23–4.81)

1.57 (0.95 –2.60)1.57 (0.95 –2.60)

1.62 (1.15–2.29)1.62 (1.15–2.29)

2.69 (2.21–3.27)2.69 (2.21–3.27)

1.39 (1.05–1.83)1.39 (1.05–1.83)

4.35 (1.42–13.35)4.35 (1.42–13.35)

Age (per 7-yr interval) *

CHF *Valvular

heart disease *

Stroke *

Mitral stenosis *

LA diameter *

Aortic regurgitation *

Hypertension *

Gender(men vs women)

* p < 0.05 ( ) 95% CI

Development of a Risk Score for AF: A Community-Based Cohort (Framingham HS) Hazard Regression Coefficient for 10-Year Risk of AF

Development of a Risk Score for AF: A Community-Based Cohort (Framingham HS) Hazard Regression Coefficient 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 ?

Risk of newly AF by duration of treated DM Risk of newly AF by level of Hb A1c

Dublin S. J Gen Intern Med 2010; 25: 853-8

Type 2 Diabetes Mellitus and Riskof Incident AF in Women

Schoen T. J Am Coll Cardiol 2012; 60: 1421–8

the risk associated with T2DM is mainly mediated by changes of other AF RF

Type-2 Diabetes Mellitus and Risk of AFMeta-Analysis of Cohort and Case-Control Studies on 108.703 Cases

Huxley RR. Am J Cardiol 2011; 108: 56-62

• Studies that had adjusted for multiple risk factors reported a smaller effect estimate compared to age-adjusted studies.(RR 1.24, 95% CI 1.06 to 1.44, vs 1.70, 1.29 to 2.22).

• The population attributable fraction of AF owing to T2DM was 2.5% (95% CI 0.1 to 3.9).

How Increased Glucose Levels and DM May Exert a Proarrhythmic Effect ?

■ No evidence to indicate that T1DM is associated with an increased risk of AFCollier A. Postgrad Med J 1987; 63: 895-897

►Insulin resistence rather than hyperglicemia is responsible for the increased risk of AF

■ Insulin resistence is also a mechanism by which hypertension and obesity are associated with increased risk of AF

Yamagishi SI. Horm Metab Res 2008; 40: 640-644Ostgren SJ. Diabetes Obes Metab 2004; 6: 367-74

■ DM and impaired glucose tolerance are associated with LVH which is a significant risk factor for AF

Rutter MK. Circulation 2003; 107: 448-454

■ Long-term inflammation may be the mech mediating the link between DM and AF

Thrombogenesis Markers in Different Type of AF

Author Journal/Year Biomarkers AF Types Results

Li-Saw-Hee FL. Eur Heart J 2001

Fibrinogen, vWF, sP-Selectin

Pxm, Pst, Prmvs Healty

Prm ↑ F, vWF and sP-S

Pxm↑ F and vWF, not sP-SPst and Healty normal level of all

Kamath S. Blood Coagul Fibrin 2002

Fibrinogen, D-dimer, vWF, sP-Selectin, β-thromboglulin

Pxm, Pst, Prmvs Controls

β-T and D-d ↑ in AF, highest in PrmF and sP-S = similar in C

Motoki H. Circ J 2009

TAT, PF4, Plasmin-Antiplasmin complex

Pxm, Prm TAT, PF4 ↑ in Pxm, PrmP-APc no ≠

Marin F. Heart 2004

D-dimer, vWF Acute AF, Prm, vs Healty vs Control

D-dimer, vWF ↑ in acAF and Prm

Wang TL. Cardiology 2004

D-dimer Acute AF vs Prm D-dimer ↑ 30 day after CV in acAF vs Prm

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

Atrial FibrillationCHA2DS2VASc Score And Stroke Rate

Atrial FibrillationCHA2DS2VASc Score And Stroke Rate

Events Rate by Stroke Risk Factors, CHADS2 Score and Anticoagulation State in 11526 Adults With AF

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

C Aimé-Sempé. J Am Coll Cardiol 1999;34:1577.

Col

agen

(M

ason

’s tr

icrh

omic

)

Elastic fibers (O

rceine)

SR

AF

Human AF Substrate: Surgical BiopsiesHuman AF Substrate: Surgical Biopsies

Neuroumoral Activation in AFIBHIGH ATRIAL PRESSURE OR VOLUME

ATRIAL FIBROSIS

ATRIAL REMODELING

■ TZDs have been proven to have - anti-inflammatory and - 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 pts with TZD use were the study cohort and 7928 pts w/out TZD use were the comparison cohort

Thiazolidinediones (Rosiglitazone)Agonists Of Peroxisome Proliferator Activated Receptor Gamma (PPAR-γ)

Can Prevent New Onset AF In Pts With Non-insulin Dependent Diabetes

Chao TF, Chen SA, Int J Cardiol 2011; 156: 199-202

-31%

PPAR-γ Activator (Pioglitazone) as Upstream Therapy for Age-Related AF in Rats

Xu D. J Cardiovasc Electrophysiol, 2012; 23: 209-217

Clinical Benefits Of TZDs On Atrial Fibrillation PreventionHome PD, et al. Rosiglitazone evaluated for cardiovascular 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. Secondary prevention of macrovascular events in patients with type 2 diabetes in the proACTIVE study (prospective pioglitazone clinical trial in macrovascular events): a randomised controlled trial

Lancet 2005;366:1279–89

DeFronzo, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance (ACT-NOW)

N Engl J Med 2011;364:1104–15

Atrial Fibrillation 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-term inflammation may be the mech mediating the link

between DM and AF

■ Rooms for further upstream Rx in AF

■ AF in diabetics patients exerts an elevated thromboembolic risk