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Diabetes Mellitus and Heart Failure:A Bidirectional Relationship
Dr. Yehia Kishk
Prof. of cardiology
Asyut University
Aswan 3rd Feb 2016
1
“TDI revealed LV diastolic dysfunction in
> 60% of asymptomatic type 2 DM”
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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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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
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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Several studies have confirmed the association between HF and DM.
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: 607-615.7
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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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 womenwhen 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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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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From Diabetes Mellitus to Heart FailureFrom Heart Failure to Diabetes MellitusFrom Diabetes Mellitus to Heart FailureFrom Heart Failure to Diabetes Mellitus
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Mechanisms of heart failure in DM
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 FailureMechanisms of heart failure in DM
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Circulation, 2007;115:3213 13
stimulates transcription
gen
era
tio
n
(Reactive Oxygen Species)
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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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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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.16
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: 225-233.17
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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• 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)
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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Therapeutic strategies for diabetic
HF and cardiomyopathy
Heart fail rev 201321
Diabetes Drugs to Use with Caution in Heart Failure
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Diabetes Drugs to Use with Caution in Heart Failure
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(Glitazones)
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?
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.
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.
27
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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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ACCF/AHA classification of HF