Ueda 2016 diabetes mellitus and heart failure - yahia kishk

1. Diabetes Mellitus and Heart Failure:
A Bidirectional Relationship
Dr. Yehia Kishk
Prof. of cardiology
Asyut University
Aswan 3rd Feb 2016
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2. “TDI revealed LV diastolic dysfunction in
> 60% of asymptomatic type 2 DM”
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3.  The prevalence of HF among patients with DM.
 The bidirectional relationship between diabetes and HF.
 Diagnostic approach of patients with suspected HF.
 Diabetes drugs to be used with caution in HF.
Objectives
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4.  Prevalence of HF in general population:
is 2%- 3% and 10-20% in age >70 yrs
 Prevalence cardiomyopathy in diabetics:
is12% and 22% in age >64 yrs
 In HF patients 27% may have T-2 DM.
Dickstein K et al. Eur Heart J;29:2388–442, 2008
Gomez-Soto FM et al. Int J Cardiol 2010. 4
Despite recent advances in therapy for HF:
Epidemiology

5. Mortality in Chronic HF
Tribouilloy C et al. Eur Heart J 2008;29:339–47.
5-years HF survival is less than 50%, irrespective of ejection fraction
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6. 6
Several studies have confirmed the association between HF and DM.

7.  Association between DM and HF that is partly
linked to CAD and HTN.
 CVD is the primary cause of death in diabetic
population.
 Coronary artery disease
 Associated hypertension,
 Heart failure and diabetic cardiomyopathy.
Loffroy R, et al Arch Cardiovasc Dis. 2009; 102: 607-615.
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8.  There is also another association between absolute
blood glucose levels and HF independent of
coexisting HTN or CAD.
 Diabetic cardiomyopathy with either systolic or
diastolic LV dysfunction in absence of clinically
significant coronary, valvular or hypertensive
disease.
Masugata H, et al.. Diabetes Res Clin Pract 2008;79:91-6.
Rubler S, et al.. Am J Cardiol 1972;30:595– 602.
Kannel WB, et al. Am J Cardiol. 1974; 34: 29-34
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9.  Diabetic cardiomyopathy was first described by
Rubler et al. in 1972 based on postmortem findings.
 In 1974 Framingham Study established the
epidemiologic link between diabetes and HF:
 The risk of HF was 2.4-fold in men and 5-fold in women.
 and remained elevated at 3.8 in men and 5.5 in women
when patients with coronary or rheumatic heart disease
were excluded
Masugata H, et al.. Diabetes Res Clin Pract 2008;79:91-6.
Rubler S, et al.. Am J Cardiol 1972;30:595– 602.
Kannel WB, et al. Am J Cardiol. 1974; 34: 29-34
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10.  UKPDS: prevalence of heart failure in type 2 DM
correlates with levels of HbA1c:
 Every 1% increase in Hgb A1c leads to 8% increase in HF
 2.3 HF cases/1000 person/yr in patients with HbA1c: <6%.
 11.9 HF /1000 person/yr in patients high HbA1c: >10%.
Stratton IM, et al. Brit Med J. 2000; 321: 405-412.
. Bertoni AG, et al. Diabetes Care. 2004; 27: 699-703..
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11. From Diabetes Mellitus to Heart FailureFrom Heart Failure to Diabetes Mellitus
From Diabetes Mellitus to Heart FailureFrom Heart Failure to Diabetes Mellitus
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Mechanisms of heart failure in DM

12.  Diabetes frequently precedes HTN, CAD and CKD
which are major risk factors for HF.
 Hypertension: pressure overload.
 IHD: diabetes accelerates the appearance and
progression of coronary atherosclerosis.
 Diabetic nephropathy: fluid retention and eventually
volume overload.
 Lipotoxicity due to accumulation of FFA in heart muscle.
Goyal BR, Mehta AA.. Hum Exp Toxicol. 2013; 32: 571-590.
Voulgari C, et al. Vasc Health Risk Manag. 2010; 6: 883-903.
From Diabetes Mellitus to Heart Failure
Mechanisms of heart failure in DM
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13. Circulation, 2007;115:321313
stimulates transcription
generation
(Reactive Oxygen Species)

14. Perivascular fibrosis (A) and fibrosis between myocytes (B) in a patient with
diabetes mellitus at autopsy
Myocardial fibrosis and myocyte hypertrophy
in diabetic cardiomyopathy
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15. A) Fibrotic infiltration.
B) Quantitative analysis of fibrosis. The
collagen volume fraction was higher in
the diabetic group than in the control
group
Myocardial fibrosis and myocyte hypertrophy
in diabetic cardiomyopathy
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16.  Decreased physical activity in HF patients may lead to
decreased insulin sensitivity hyperglycemia.
 Increased catecholamine levels and sympathetic
activity stimulate gluconeogenesis and glycogenolysis.
 Lenient monitoring for impaired glucose metabolism in
early stages of HF.
From Heart Failure to Diabetes Mellitus
 Hypoperfusion and congestion of the pancreas and
liver, which may impair their ability to regulate metabolic
homeostasis.
 Adverse effects of HF treatments, such as β-blockers
and diuretics in blood glucose control.
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17. Structural changes include:
(i) LV hypertrophy, assessed by 2DE or CMR imaging
(ii) increased integrated backscatter in the LV (septal and posterior wall);
(iii) late Gd enhancement of the myocardium in CMR.
Functional changes are due to:
(i) LV diastolic dysfunction, assessed by PWD and TDI;
(ii) LV systolic dysfunction, demonstrated by TDI/SRI;
(iii) limited systolic and/or diastolic functional reserve, assessed by
exercise TDI.
Metabolic changes are primarily associated with:
(i) a reduced ratio of cardiac phosphocreatine to adenosine triphosphate;
(ii) elevated myocardial triglyceride content.
Approach to Diagnosis of Diabetic Cardiomyopathy
Using 2DE, TDI, CMR
Rijzewijk LJ, et al.. J Am Coll Cardiol. 2010; 56: 225-233.
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18. J Am Coll Cardiol. 2003;42(3):454-457.
Wall motion abnormalities
The Echocardiographic Cascade of
Diabetic Cardiomyopathy.
Glycation cause early structural alteration
with accumulation of myocardial CT which induces:
Each of these variables is detected by its specific ultrasound technology
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19. • Normal person with good diastolic function; high E and e', normal E/e'.
• Patient with diastolic dysfunction without increased filling pressure;:low E and e', normal E/e' ratio.
• Patient with diastolic dysfunction and increased filling pressure;: high E, low e' and high E/e.
Relation between mitral flow and mitral annulus velocity
(PWD/TDI)
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reduction of annular (e΄)
Combination of pulsed TDI velocity of the medial mitral annulus during
passive filling (e΄) with the early passive transmitral inflow velocity (E)

20. Boyer Jk et al. Am J Cardiol. 2004; 93: 870-875.
 In asymptomatic type 2 DM, TDI revealed LV diastolic
dysfunction in 63%, while abnormal transmitral LV filling
pattern was detected in only 46%.
Boyer JK, et al. Am J Cardiol. 2004; 93: 870-875.
 Overt HF and compromised LV systolic function
occurs in advanced stages of HF.
 Forward HF (weakness, fatigue, angina, syncope)
 Backward HF (dyspnea, raised jugular vein pressure,
lower extremity edema, hepatomegaly).
Clinical Presentation and
Diagnostic Approach
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21. Therapeutic strategies for diabetic
HF and cardiomyopathy
Heart fail rev 201321

22. Diabetes Drugs to Use with Caution in Heart Failure
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23. Diabetes Drugs to Use with Caution in Heart Failure
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(Glitazones)

24. Aggressive Glycemic Control
 Is important as it decrease FFA oxidation by
myocardial cells and increase glucose utilization.
 Does intensive glycemic control associated with better
cardiovascular outcomes?
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25.  DCC trial and UKPD study provided evidence that
Intensive glycemic control prevents the development and
progression of microvascular complications in patients
with type 1 or type 2 diabetes.
 The 2013 ESC Guidelines on diabetes, pre-diabetes,
and CVD consider tight glycemic control (HbA1c<7%) as
a class I indication to decrease microvascular
complications and class IIa for the prevention of CVD.
 ACCORD, ADVANCE, and VADT trials revealed no
significant effect of intensive glycemic control on
mortality or on amelioration of cardiovascular events.
Miki T,. Heart Fail Rev. 2013; 18: 149-166.
Rydén L, et al. Nat Rev Cardiol. 2010; 7: 369-375.
Bloomgarden ZT. Diabetes Care. 2008; 31: 1913-1919.
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26. Conclusions
 HF and DM frequently co-exist in a bidirectional
relationship.
 At the moment several pathophysiological
connections have been proposed.
 Both DM and HF are characterized by high morbidity
and mortality, and treatment must target the overall
improvement as DM treatment can decompensate HF
and vice versa.
 Diabetes Drugs to be Used with Caution in Heart
Failure.
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27. 28

28. In this apical 4-chamber view (focus on left ventricle), the sample is obtained at the septal region of the mitral annulus (yellow
circle).Y-axis represents myocardial velocity (cm/s) and the X-axis represents time. The velocity curve has a positive peak (s′)
during systole and two negative peaks during diastole, an early (e′) and a late (a′) peak.
Myocardial velocity curve by
color tissue Doppler imaging
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29. ACCF/AHA classification of HF