ueda2011 ak-diabetic cardiomyopathy_d.ali

1. DiabeticDiabetic
CardiomyopathyCardiomyopathy
Prof .Ali .M. KaseemProf .Ali .M. Kaseem
Internal Medicine and CardiologyInternal Medicine and Cardiology
DepartmentDepartment
Sohag Faculty of MedicineSohag Faculty of Medicine

2. AgendaAgenda
 Magnitude of the problemMagnitude of the problem
 Definition , pathophysiology and riskDefinition , pathophysiology and risk
factors of diabetic cardiomyopathyfactors of diabetic cardiomyopathy
 ManagementManagement
 Role of RAAS inhibitors and B.BRole of RAAS inhibitors and B.B
 SummarySummary

3. 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 riskEvery 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 , LVHThe 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 systolicDM is an independent risk factor for death in patients with systolic
dysfunction.dysfunction.

6. Risk of Different Outcomes Associated
with Diabetes in HF. LEF and HF.PEF
MacDonald M R et al. EHJ 2008;29:1377-85

9. Diabetic CardiomyopathyDiabetic Cardiomyopathy
DCMDCM
 Some diabetic patients do not have obviousSome 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.

10. DefinitionDefinition
Diabetic cardiomyopathy refersDiabetic cardiomyopathy refers
to myocardial disease into myocardial disease in
diabetic subjects that cannotdiabetic subjects that cannot
be ascribed to hypertension,be ascribed to hypertension,
CAD, or any other knownCAD, or any other known
cardiac diseasecardiac disease

11. DCM

12. 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-Schiff (PAS)-Interstitial fibrosis and infiltration with periodic acid-Schiff (PAS)-
positive materialspositive materials
 Alterations in the myocardial capillary basement membranesAlterations in the myocardial capillary basement membranes
 Intramyocardial microangiopathyIntramyocardial microangiopathy
Myocardial fibrosis correlates with increased risks forMyocardial fibrosis correlates with increased risks for
neuropathy, nephropathy, and retinopathyneuropathy, nephropathy, and retinopathy

13. Risk factors for DCM
1- Hyperglycemia
2-Insulin resistance
3-Hypertension
4-Dyslipidemia
5-Obesity
6-Diabetic nephropathy

14. Nephropathy

19. MANAGEMENT OF CARDIOMYOPATHYMANAGEMENT OF CARDIOMYOPATHY
AND HEART FAILURE IN DIABETESAND HEART FAILURE IN DIABETES
Control of risk factorsControl of risk factors
Tight BP and glycemic controlTight BP and glycemic control
Treat etiologic / aggravatingTreat etiologic / aggravating
factorsfactors
LifestyleLifestyle
Team workTeam work

20. Can glucose control improveCan glucose control improve
diastolic functiondiastolic 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.

21. Can glucose control improveCan glucose control improve
diastolic functiondiastolic 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.

24. 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 follow-upBP lowered to avg. 144/82 (controls-154/87); 9 yr follow-up
EndpointEndpoint Risk Reduction(%) P ValueRisk Reduction(%) P Value
Any diabetes related endpointAny diabetes related endpoint 2424 0.00460.0046
Diabetes related deathsDiabetes related deaths 3232 0.0190.019
Heart failureHeart failure 5656 0.00430.0043
StrokeStroke 4444 0.0130.013
Myocardial infarctionMyocardial infarction 2121 NSNS
Microvascular diseaseMicrovascular disease 3737 0.00920.0092
UKPDS. BMJ. 317: 703-713. 1998.

25. DRUG THERAPY OF HEART FAILUREDRUG THERAPY OF HEART FAILURE
IN DIABETESIN DIABETES
 Treating heart failure and diabetes separatelyTreating heart failure and diabetes separately
 Drug therapy :Drug therapy :
• ACEI (ARBs )ACEI (ARBs )
• BBBB
• Aldosterone blocadeAldosterone blocade
• CCBCCB
• DiureticsDiuretics
• StatinsStatins

26. Disease Progression
Hypertrophy, apoptosis, ischemia,
arrhythmias, remodeling, fibrosis
Angiotensin II Norepinephrine
Neurohormonal ActivationNeurohormonal Activation
inin HF and DMHF and DM
RAAS inhibitors
Beta blockers

27. ACEI and ARBsACEI and ARBs
HOPE ,SOLVD, RESOLVD , andHOPE ,SOLVD, RESOLVD , and
Assessment of Treatment withAssessment of Treatment with
Lisinopril and Survival trialsLisinopril and Survival trials
 Greater benefits with ACEI inGreater 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..

28. ACEI in DM (Ramipril)

30. BB in HFBB in HF
20102010
 BB are recommended for all patients with HFBB are recommended for all patients with HF
due to left ventricular systolic dysfunction,due to left ventricular systolic dysfunction,
including :including :
 Older adultsOlder adults
 Patients with :Patients with :
1)1) Diabetes mellitusDiabetes mellitus
2)2) Peripheral vascular diseasePeripheral vascular disease
3)3) Erectile dysfunctionErectile dysfunction
4)4) Interstitial pulmonary diseaseInterstitial pulmonary disease
5)5) COPD without reversibilityCOPD without reversibility
NICE GUIDELINES (2010)NICE GUIDELINES (2010)

31. 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.
Follow­up (months) Time (days)
CIBIS-II
Log rank P=.00006
Bisoprolol
Placebo
n=2647
0 200 400 600 800
Probabilityofsurvival
COPERNICUS
Survival(%)
34%Mortality: 34% 35%
Carvedilol
Placebo
P=.00014 (unadjusted)
P=.0014 (adjusted)
n=2289
Months
0 4 8 12 16 20 24 28
MERIT-HF
Cumulativemortality(%)
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
0
0 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

33. Drugs effect and Insulin sensitivity (ISDrugs effect and Insulin sensitivity (IS((
Decreased ISDecreased IS
High-dose thiazideHigh-dose thiazide
Diuretics are perhaps bestDiuretics are perhaps best
avoided in DM patient .avoided in DM patient .
Loop diureticsLoop diuretics
have ahave a lesser effect onlesser effect on
glucose metabolism andglucose metabolism and
are preferred to thiazideare preferred to thiazide
agents.agents.
Improve ISImprove IS
Angiotensin-convertingAngiotensin-converting
enzyme inhibitorsenzyme inhibitors
Angiotensin-II receptorAngiotensin-II receptor
blockersblockers
Vasodilators.Vasodilators.

35. Special considrationSpecial considration
Reduce polypharmacyReduce polypharmacy
Adverse drug reactions :Adverse drug reactions :
Glitazones , NSAID , DiuriticsGlitazones , NSAID , Diuritics
Electrolyte abnormalitiesElectrolyte abnormalities
Renal and hepatic functionsRenal and hepatic functions

37. SUMMARYSUMMARY
 Patients with DM have a high risk for LVD and a poor prognosis oncePatients with DM have a high risk for LVD and a poor prognosis once
they develop HF.they develop HF.
 Diabetic cardiomyopathy refers to LVD in diabetic patients with noDiabetic cardiomyopathy refers to LVD in diabetic patients with no
evidence of CAD or any other known cardiac disease .evidence of CAD or any other known cardiac disease .
 The pathophysiology of diabetic cardiomopathy includes : functional ,The pathophysiology of diabetic cardiomopathy includes : functional ,
anatomical and metabolic abnormalities .anatomical and metabolic abnormalities .
 Choice of drugs for the management of HF in diabetic patients shouldChoice of drugs for the management of HF in diabetic patients should
be directed at changing the natural history of the disease.be directed at changing the natural history of the disease.
 ACEI and BB should be given as first-line therapy in diabeticACEI and BB should be given as first-line therapy in diabetic
cardiomyopathy .cardiomyopathy .
 Aggressive risk-factor modification in addition to tight BP andAggressive risk-factor modification in addition to tight BP and
glycemic control are crucial in the management diabeticglycemic control are crucial in the management diabetic
cardiomyopathy .cardiomyopathy .

38. ‫جمهورية‬ ‫رئيس‬ ‫مطلوب‬‫جمهورية‬ ‫رئيس‬ ‫مطلوب‬
‫ناصيتين‬ ‫على‬ ‫لقطة‬ ‫بلد‬‫ناصيتين‬ ‫على‬ ‫لقطة‬ ‫بلد‬
‫احمر‬ ‫وبحر‬ ‫ابيض‬ ‫بحر‬‫احمر‬ ‫وبحر‬ ‫ابيض‬ ‫بحر‬
‫بحيرات‬ ‫وخمس‬ ‫نهر‬ ‫بها‬‫بحيرات‬ ‫وخمس‬ ‫نهر‬ ‫بها‬
33‫وقناة‬ ‫اهرامات‬‫وقناة‬ ‫اهرامات‬
‫يساع‬ ‫ميدان‬‫يساع‬ ‫ميدان‬55‫مليون‬‫مليون‬
‫تشطيب‬‫تشطيب‬8585‫مواطن‬ ‫مليون‬‫مواطن‬ ‫مليون‬
‫وابنه‬ ‫ديكتاتور‬ ‫استعمال‬‫وابنه‬ ‫ديكتاتور‬ ‫استعمال‬
‫مرفوعة‬‫مرفوعة‬3030‫سنة‬‫سنة‬
‫المسروق‬ ‫العفش‬ ‫استعادة‬ ‫بعد‬ ‫التسليم‬‫المسروق‬ ‫العفش‬ ‫استعادة‬ ‫بعد‬ ‫التسليم‬