Diabetic Diabetic CardiomyopathyCardiomyopathy

Prof .Ali .M. KaseemProf .Ali .M. KaseemInternal Medicine and Cardiology Internal Medicine and Cardiology

DepartmentDepartment Sohag Faculty of MedicineSohag Faculty of Medicine

AgendaAgenda Magnitude of the problemMagnitude of the problem Definition , pathophysiology and Definition , pathophysiology and

risk factors of diabetic risk factors of diabetic cardiomyopathycardiomyopathy

ManagementManagement Role of RAAS inhibitors and B.B Role of RAAS inhibitors and B.B SummarySummary

FACTSFACTS The percentage of patients with DM and heart failure in different

studies ranged between 20-26%.

DM is 2-5 times more common patients with HF.DM is 2-5 times more common patients with HF.

Every 1% increase in HA1c translates into 15 % increase the risk Every 1% increase in HA1c translates into 15 % increase the risk of developing HF.of developing HF.

The frequency of risk factors for HF ( IHD , HT , dyslipidemia , LVH The frequency of risk factors for HF ( IHD , HT , dyslipidemia , LVH ) is increased in diabetics .) is increased in diabetics .

DM is an independent risk factor for death in patients with systolic DM is an independent risk factor for death in patients with systolic dysfunction. dysfunction.

Risk of Different Outcomes Associated with Diabetes in HF. LEF and HF.PEF

MacDonald M R et al. EHJ 2008;29:1377-85

Diabetic CardiomyopathyDiabetic CardiomyopathyDCMDCM

Some diabetic patients do not have obvious Some diabetic patients do not have obvious ischemic insults that lead to progressive HF.ischemic insults that lead to progressive HF.

The entity of diabetic cardiomyopathy was originally described in 1972 on the basis of observations in four diabetic patients who presented with HF without evidence of hypertension, CAD, valvular or congenital heart disease.

Anatomical dissection of the myocardium revealed LVH and myocardial fibrosis.

DefinitionDefinitionDiabetic cardiomyopathy Diabetic cardiomyopathy refers to myocardial refers to myocardial disease in diabetic disease in diabetic subjects that cannot be subjects that cannot be ascribed to hypertension, ascribed to hypertension, CAD, or any other known CAD, or any other known cardiac diseasecardiac disease

DCM

Evidences in favour of diabetic Cardiomyopathy

Functional changes : LV diastolic dysfunction LV systolic dysfunction Anatomical changes : Myocyte hypertrophyMyocyte hypertrophy Interstitial fibrosis and infiltration with periodic acid-Interstitial fibrosis and infiltration with periodic acid-

Schiff (PAS)-positive materialsSchiff (PAS)-positive materials Alterations in the myocardial capillary basement Alterations in the myocardial capillary basement

membranes membranes Intramyocardial microangiopathyIntramyocardial microangiopathyMyocardial fibrosis correlates with Myocardial fibrosis correlates with

increased risks for neuropathy, increased risks for neuropathy, nephropathy, and retinopathynephropathy, and retinopathy

Risk factors for DCM 1- Hyperglycemia

2-Insulin resistance

3-Hypertension4-Dyslipidemia

5-Obesity6-Diabetic nephropathy

Nephropathy

MANAGEMENT OF MANAGEMENT OF CARDIOMYOPATHY AND HEART CARDIOMYOPATHY AND HEART

FAILURE IN DIABETESFAILURE IN DIABETES

Control of risk factorsControl of risk factorsTight BP and glycemic Tight BP and glycemic controlcontrol

Treat etiologic / Treat etiologic / aggravating factorsaggravating factors

LifestyleLifestyleTeam workTeam work

Can glucose control Can glucose control improve diastolic functionimprove diastolic function? ?

The UKPDS evaluated the relationship between exposure to glycemia over time and the development of diabetic cardiomyopathy in patients with type 2 diabetes :

For each 1% reduction in mean HbA1c, there was a 14% associated decrease in risk for myocardial infarction and a 16% decrease in risk for heart failure.

Can glucose control Can glucose control improve diastolic functionimprove diastolic function? ?

Epidemiological analysis of a prospective, multicenter, population-based study of patients with newly diagnosed type 2 DM:

Good glycemic control was associated with a lower incidence of diabetic cardiomyopathy (27% vs 9%), whereas postprandial blood glucose levels were among the independent predictors for cardiovascular morbidity and mortality.

Vasc Health Risk Manag. 2009;5:859–871.

UKPDS Blood Pressure Study:UKPDS Blood Pressure Study:Tight vs. Less Tight ControlTight vs. Less Tight Control

1148 type 2 patients1148 type 2 patients BP lowered to avg. 144/82 (controls-154/87); 9 yr BP lowered to avg. 144/82 (controls-154/87); 9 yr

follow-upfollow-up

EndpointEndpoint Risk Reduction(%) P ValueRisk Reduction(%) P Value

Any diabetes related endpointAny diabetes related endpoint 2424 0.0046 0.0046Diabetes related deathsDiabetes related deaths 3232 0.019 0.019Heart failureHeart failure 5656 0.0043 0.0043StrokeStroke 4444 0.013 0.013Myocardial infarctionMyocardial infarction 2121 NS NSMicrovascular diseaseMicrovascular disease 3737 0.0092 0.0092

UKPDS. BMJ. 317: 703-713. 1998.

DRUG THERAPY OF HEART DRUG THERAPY OF HEART FAILURE IN DIABETESFAILURE IN DIABETES

Treating heart failure and diabetes Treating heart failure and diabetes separately separately

Drug therapy :Drug therapy :• ACEI (ARBs )ACEI (ARBs )• BBBB• Aldosterone blocadeAldosterone blocade• CCBCCB• DiureticsDiuretics• StatinsStatins

Disease ProgressionHypertrophy, apoptosis, ischemia,arrhythmias, remodeling, fibrosis

Angiotensin II Norepinephrine

Neurohormonal ActivationNeurohormonal Activation in in HF and DM HF and DM

RAAS inhibitorsBeta blockers

ACEI and ARBsACEI and ARBsHOPE ,SOLVD, RESOLVD , and HOPE ,SOLVD, RESOLVD , and

Assessment of Treatment with Assessment of Treatment with Lisinopril and Survival trialsLisinopril and Survival trials

Greater benefits with ACEI in Greater benefits with ACEI in diabetic subgroups with HF. diabetic subgroups with HF.

Increase responsiveness to insulin.Increase responsiveness to insulin. Reduction in Hb A1cReduction in Hb A1c. .

ACEI in DM (Ramipril)

BB in HFBB in HF 20102010 BB are recommended for all patients with BB are recommended for all patients with

HF due to left ventricular systolic HF due to left ventricular systolic dysfunction, including :dysfunction, including :

Older adults Older adults Patients with :Patients with :

1)1) Diabetes mellitus Diabetes mellitus 2)2) Peripheral vascular disease Peripheral vascular disease 3)3) Erectile dysfunction Erectile dysfunction 4)4) Interstitial pulmonary diseaseInterstitial pulmonary disease5)5) COPD without reversibilityCOPD without reversibility

NICE GUIDELINES (2010)NICE GUIDELINES (2010)

ER, extended release.

Adapted from: MERIT-HF Study Group. Lancet. 1999;353:2001 2007.CIBIS-II Investigators. Lancet. 1999;353:9 13.Packer M, et al. N Engl J Med. 2001;344:1651 1658.

Follow up (months) Time (days)

CIBIS II

Log rank P=.00006

Bisoprolol

Placebo

n=2647

0 200 400 600 800

Prob

abili

ty o

f sur

viva

l

COPERNICUS

Surv

ival

(%)

34%Mortality: 34% 35%

Carvedilol

Placebo

P=.00014 (unadjusted)P=.0014 (adjusted)

n=2289

Months0 4 8 12 16 20 24 28

MERIT HF

Cum

ulat

ive

mor

talit

y (%

) 20

15

10

5

0

P=.0062 (adjusted)P=.00009 (nominal)

Placebo

n=3991

.9

.8

.7

.6

.5

.4

.3

.2

.1

1.0

00 3 6 9 12 15 18 21

ER Metoprolol Succinate

Beta Blockers Decrease Mortality in Mild to Advanced Symptomatic HF

100

90

80

70

60

50

Drugs effect and Insulin sensitivity Drugs effect and Insulin sensitivity (IS)(IS)

Decreased ISDecreased ISHigh-dose High-dose

thiazide thiazide Diuretics are perhaps Diuretics are perhaps

best avoided in DM best avoided in DM patient . patient .

Loop diureticsLoop diuretics have ahave a lesser effect on lesser effect on

glucose metabolism glucose metabolism and are preferred to and are preferred to thiazide agents.thiazide agents.

Improve ISImprove IS Angiotensin-Angiotensin-

converting converting enzyme inhibitors enzyme inhibitors

Angiotensin-II Angiotensin-II receptor blockersreceptor blockers

Vasodilators. Vasodilators.

Special considrationSpecial considrationReduce polypharmacy Reduce polypharmacy Adverse drug reactions : Adverse drug reactions :

Glitazones , NSAID , DiuriticsGlitazones , NSAID , DiuriticsElectrolyte abnormalitiesElectrolyte abnormalitiesRenal and hepatic Renal and hepatic functionsfunctions

SUMMARYSUMMARY Patients with DM have a high risk for LVD and a poor Patients with DM have a high risk for LVD and a poor

prognosis once they develop HF.prognosis once they develop HF.

Diabetic cardiomyopathy refers to LVD in diabetic patients Diabetic cardiomyopathy refers to LVD in diabetic patients with no evidence of CAD or any other known cardiac disease with no evidence of CAD or any other known cardiac disease . .

The pathophysiology of diabetic cardiomopathy includes : The pathophysiology of diabetic cardiomopathy includes : functional , anatomical and metabolic abnormalities .functional , anatomical and metabolic abnormalities .

Choice of drugs for the management of HF in diabetic Choice of drugs for the management of HF in diabetic patients should be directed at changing the natural history patients should be directed at changing the natural history of the disease.of the disease.

ACEI and BB should be given as first-line therapy in ACEI and BB should be given as first-line therapy in diabetic cardiomyopathy . diabetic cardiomyopathy .

Aggressive risk-factor modification in addition to tight BP Aggressive risk-factor modification in addition to tight BP and glycemic control are crucial in the management and glycemic control are crucial in the management diabetic cardiomyopathy . diabetic cardiomyopathy .

جمهورية رئيس جمهورية مطلوب رئيس مطلوب ناصيتين على لقطة ناصيتين بلد على لقطة بلد احمر وبحر ابيض احمر بحر وبحر ابيض بحر بحيرات وخمس نهر بحيرات بها وخمس نهر بها33 وقناة وقناة اهرامات اهرامات يساع يساع ميدان مليون مليون 55ميدان مواطن 8585تشطيب تشطيب مواطن مليون مليون وابنه ديكتاتور وابنه استعمال ديكتاتور استعمال سنة سنة 3030مرفوعة مرفوعة المسروق العفش استعادة بعد المسروق التسليم العفش استعادة بعد التسليم