Diabetes Mellitus and Heart Failure:A Bidirectional Relationship

Dr. Yehia Kishk

Prof. of cardiology

Asyut University

Aswan 3rd Feb 2016

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“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?

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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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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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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