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 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

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)

1.02 (0.77–1.35)

2.67 (1.57– 4.55)

3.27 (2.23–4.81)

1.57 (0.95 –2.60)

1.62 (1.15–2.29)

2.69 (2.21–3.27)

1.39 (1.05–1.83)

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

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-SPxm↑ 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

AF increases of stroke risk 4-5 fold

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

(Mas

on’s

tric

rhom

ic)

Elastic fibers (O

rceine)

SR

AF

Human 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