The Electrical System
Of The Sweet Heart
Atrial Fibrillation In
Diabetics:
A Turning Point In
Life Expectancy
G.L. Botto, MD, FACC, FESC
U.O. Cardiologia
U.O.Elettrofisiologia
Ospedale Sant’Anna, Como
AFIB Within The Cardiovascular Continuum
Remodeling
Ventricular
dilation
MI
HF
End-stage
microvascular
heart disease
Atherosclerosis and
LVH
Risk factors
(diabetes,
hypertension)
Atrial fibrillation
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
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
Furberg CD. Am J Cardiol 1994; 74: 236-241.
8
12
* p < 0.05
(
16
) 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 Risk
of Incident AF in Women
the risk associated with T2DM is mainly mediated by changes of other AF RF
Schoen T.
J Am Coll Cardiol
2012; 60: 1421–8
Type-2 Diabetes Mellitus and Risk of AF
Meta-Analysis of Cohort and Case-Control Studies on 108.703 Cases
• 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).
Huxley RR. Am J Cardiol 2011; 108: 56-62
How Increased Glucose Levels and DM
May Exert a Proarrhythmic Effect ?
■ No evidence to indicate that T1DM is associated with an increased risk of AF
Collier 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: 640-644
Ostgren 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, Prm
vs Healty
Prm ↑ F, vWF and sP-S
Kamath S.
Blood Coagul Fibrin
2002
Fibrinogen, D-dimer,
vWF, sP-Selectin,
β-thromboglulin
Pxm, Pst, Prm
vs Controls
β-T and D-d ↑ in AF, highest in
Prm
F and sP-S = similar in C
Motoki H.
Circ J
2009
TAT, PF4, PlasminAntiplasmin
complex
Pxm, Prm
TAT, PF4 ↑ in Pxm, Prm
P-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
Pxm↑ F and vWF, not sP-S
Pst and Healty normal level of all
CT Scan in an AFIB Patient With
Ischemic Stroke in The Territory of the MCA
AF increases of stroke risk 4-5 fold
Atrial Fibrillation
CHA2DS2VASc 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
AF
Elastic fibers (Orceine)
SR
Colagen (Mason’s tricrhomic)
Human AF Substrate: Surgical Biopsies
C Aimé-Sempé. J Am Coll Cardiol 1999;34:1577.
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-insulin Dependent Diabetes
■
■
■
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
-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 Cardiovasc Electrophysiol, 2012; 23: 209-217
Clinical Benefits Of TZDs On
Atrial Fibrillation Prevention
Home 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 Diabetics
DM 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