1. DIABETIC
CARDIOMYOPATHY

2. Introduction
 Obesity and sedentary life style.
 By 2025 300 million will be affected
by Diabetes Mellitus.
 Cardiovascular disease accounts for
80% of death among diabetic patients.

3. Definition
 “A distinct entity characterized by the
presence of abnormal myocardial
performance or structure in the
absence of epicardial coronary artery
disease, hypertension and significant
valvular disease.”
 First described in 1972.(Ruber et al)
 On the basis of observations in 4
diabetic patients without evidence of
HT, CAD, valvular or congenital heart
disease.

4. Epidemiology
 Diabetes affects 180 million people
worldwide.
 2/3 of patients with established CVD
have impaired glucose homeostasis;
affects 30% of heart failure patients.
 Every 1% increase in HBA1c leads to
an 8% increase in heart failure.

5.  In United Kingdom Prospective
Diabetes Study(UKPDS), it was found
that
 For HBA1c <6%, there occurred 2.3
HF events /100 person – years.
 For HBA1c >10%, there occurred 11.9
HF events /100 person – years
 Prevalence of HF in general
population: 1-4%.
 Prevalence of HF in diabetic
population: 15%.

6. Pathology
 Enhanced thickening of capillary
basement membrane.
 Myocellular atrophy and hypertrophy.
 Myocardial and interstitial fibrosis.
 Fat droplet deposition.

7. Other characteristics
 Early changes in diastolic function –
affects up to 75% asymptomatic
diabetic patients.
 Collagen deposition.
 Presence of advanced glycosylation
end products(AGEs).
 Late compromise of LV systolic
function.

8. Pathogenesis
1) HYPERGLYCEMIA –
 Excess AGE and Reactive Oxygen
Species(ROS) formation with
deactivation of NO.
 Myocardial collagen deposition and
fibrosis.

10. 2) FATTY ACIDS
 Impaired glycolysis, pyruvate
oxidation, lactate uptake results in
apoptosis.
 Alteration of myocardial bioenergetics
and contraction/relaxation coupling.

11. 3) PROTEIN KINASE C
 Activation of DAG/PKC signal
tranduction pathway
 Reduction in tissue blood flow.
 Increased vascular permeability.
 Alterations in neovascularization.
 Enhanced extracellular matrix
deposition.

12. 4) RENIN ANGIOTENSIN SYSTEM(RAS)
 Activation of stretch receptors in heart
activates RAS and the SNS 
Cardiomyocyte hypertrophy and
apoptosis.
5) ALDOSTERONE INDUCED FIBROSIS
Existence of local cardiac renin-
angiotensin-aldosterone system have
been demonstrated.
 Myofibroblast growth with interstitial and
focal perivascular accumulation of
collagen.

13. 6) HYPOXIA INDUCED FACTOR 1/
VASCULAR ENDOTHELIAL
GROWTH FACTOR
 HIF - 1α activation via hypoxia/free
radicals induces angiopoietin,
PGF,PDGF-β and VEGF.
 In diabetes, VEGF and its receptors
are decreased significantly leading to
impaired angiogenesis.

14. 7) ENDOTHELIAL DYSFUNCTION
 Impaired endothelial NO production.
 Increased vasoconstrictor
prostaglandins, glycated proteins,
endothelium adhesion molecules
,platelet and vascular growth factors
which enhance vasomotor tone and
vascular permeability and limit growth
and remodelling .

15. 8) AUTONOMIC NEUROPATHY
 Decreased
sympathetic/parasympathetic
myocardial innervation with impaired
coronary resistance vessel vasodilator
response .
 Impaired ventricular diastolic filling.

18. Stages of diabetic
STAGES
cardiomyopathy
CHARACTERISTICS FUNCTIONAL STRUCTURAL METHODS
FEATURES FEATURES
Early stage Depletion of GLUT4 No overt functional Normal LV size, wall Sensitive
Increased FFA abnormalities or thickness, and mass methods such as
Carnitine deficiency possible strain, strain rate,
Ca2 homeostasis changes overt diastolic and
Insulin resistance dysfunction myocardial tissue
but normal ejection velocity
fraction
Middle stage Apoptosis and necrosis Abnormal diastolic Slightly increased LV Conventional
Increased AT II dysfunction and mass, echocardiograph
Reduced IGF-I normal or wall thickness, or size y or
Increased TGF-1 slightly decreased sensitive
Mild CAN ejection methods such as
fraction strain, strain rate,
and
myocardial tissue
velocity
Late stage Microvascular changes Abnormal diastolic Significantly Conventional
Hypertension dysfunction and increased LV echocardiograph
CAD ejection size, wall thickness, y
Severe CAN fraction and
mass

19. Clinical features
 Symptoms
-Typically pts c/o months of fatigue,
weakness, reduced exercise
tolerance
due to CHF.
-May also present as Arrythmia
or Sudden Death.
 Physical Signs
-Tachycardia
-Jugular venous distension
-Gallop heart sounds

20. Diagnosis
 CXR- Cardiomegaly
 ECG- Normal or low QRS voltage , abn
axis, non specific ST seg abnormalities,
conduction defects.
 2D Echo
 Tissue doppler echo
 Intravenous contrast echo
 Computed tomography
 Magnetic resonance imaging

21. 2D ECHO
 Preserved LV ejection fraction.
 Reduced early diastolic filling.
 Prolongation of isovolumetric
relaxation and increased atrial filling.
 Pre – ejection period(PEP) increased.
 LV ejection time(LVET)decreased.
 PEP/LVET increased.

22. GRADES OF DIASTOLIC DYSFUNCTION
 Grade 1- Abnormal Relaxation Pattern
 Reversal of E/A ratio
 Develop normally with age.
 Patients will not have any symptoms of
heart failure.
 E/A ratio- Ratio between early(E) and
late (atrial – A) ventricular filling velocity.
 E caused by accumulation of blood in the
atria during previous systole.
 A created by atrial contraction.

23. GRADE II - Pseudonormal Filling Dynamics
 Moderate diastolic dysfunction.
 Elevated left atrial filling pressure.
 Symptoms of heart failure.
 E/A ratio appears normal.
GRADE III – Reversible Restrictive Diastolic
dysfunction
 Reversal of diastolic abnormalities on echo
on performing Valsalva maneuver.
 E/A ratio > 2.
GRADE IV – Fixed Restrictive Diastolic
Dysfunction
 No reversibility of echo abnormalities.
 E/A ratio > 2

25. Trans-mitral valve spectral Doppler flow pattern
in a normal subject (upper panel), in a patient
with mild
diastolic dysfunction (abnormal relaxation;
middle panel),
and in a patient with severe (restrictive) diastolic
dysfunction (lower panel)

26. TISSUE DOPPLER ECHO
 In standard echo , high velocity low
amplitude filter looks at blood flow
through valves .
 TDI applies high velocity low
amplitude filter to myocardium thus
looking at myocardial tissue velocities.
 Results independent of pre load.
 Subtle systolic and diastolic
dysfunction can be defined.

27. INTRAVENOUS CONTRAST ECHO
 Non invasive means of assessing
integrity of the coronary
microcirculation and myocardial
perfusion.
 Relies on resonance of microbubble
contrast agents when excited by
diagnostic usg freq. producing
increased backscatter from blood.

28. Contrast echocardiographic sequence with microbubble contrast agent
defining myocardial perfusion within
different myocardial segments
Frame i) is immediately following a high power ultrasound flash which destroys
the micro-bubbles within the myocardium. Frames ii)–iv) show replenishment
of
micro-bubbles in the septum and lateral walls within 2 heartbeats. A clear

29. Treatment
GLYCAEMIC CONTROL
LIFESTYLE MODIFICATION
β BLOCKERS
 Chronic stimulation of SNS  inc.
heart rate and altered gene
expression  cardiac remodelling in
both HF and diabetes.
 Traditionally β blockers were not used
( insulin resistance and hypoglycemia
unawareness).

30.  But with recent advances in
understanding of heart failure and
importance of SNS, β blockers have
become essential in treatment of HF.
 COPERNICUS(Carvedilol Prospective
Randomized Cumulative Survival)
study
 67% reduction in morbidity and
mortality in HF patients treated with
carvedilol.

31. ACE INHIBITORS
 HOPE( Heart Outcomes Prevention
Evaluation) study
 Decreased cardiovascular morbidity
and mortality in diabetic patients.
 33% reduction in rate of development
of new HF.
 ARBs – additive effects on
hemodynamic measurements,
neurohormonal activity and LV
remodelling with ACE ≠.

32. Cardiovascular morbidity and mortality in the
HOPE study, illustrating a greater benefit in the
diabetic patients
ALL PATIENTS DIABETIC PATIENTS
Death from 26% 37%
cardiovascular causes
MI 20% 22%
Stroke 32% 33%
All- cause mortality 16% 24%
Revascularisation 15% 17%

33. STATINS
 Direct effect on cholesterol
metabolism.
 Augments collateral blood flow
downstream of activated plaques.
 Enhances endothelial cell NO
synthase activity.
 Prevents upregulation of VEGF
mRNA.
 Prevents AGE related damage.

34. Newer therapeutic directions
 PARP inhibitors[poly(ADP-ribose)
polymerase 1]
 Functions as DNA-nick-sensor enzyme.
 Hyperglycemia overproduction of
mitochondrial superoxideDNA strand
breaksactivation of PARPinhibits
GAPDHaccumulation of glycolytic
intermediatesactivate major
transducers of hyperglycemic
damage(AGE formation and PKC
pathway).
 PARP inhibitors block all those
pathways.
 Trials are going on.

35. THANKS