1. DIASTOLIC DYSFUNCTION
AMONG ELDERLY
WITH DIABETES MELLITUS
Dr Doha Rasheedy
Assistant lecturer of geriatric medicine
Geriatrics Intensive care unit
Geriatric medicine department
Ain Shams University

2.  Nearly half of HF patients have normal LV
systolic function (diastolic dysfunction).
 Diastolic dysfunction is a major
contributor to hospital admissions among
elderly population.
 Associated with high morbidity and
mortality.
.(Zile and Brustaert, 2002)

3.  Diastolic dysfunction is abnormality of
diastolic distensibility, filling, or
relaxation of the left ventricle.
 When clinical syndrome of heart
failure develop it is called Diastolic
heart failure .
(Aurigemma and Gaash,2004)

4.  The mechanical abnormalities in diastole
are caused mainly by ventricular
relaxation (impaired lusiotrophy ) and/or 
ventricular stiffness.

5. Aging and
diastolic
function

6. Aging is an independent risk for
diastolic dysfunction because:
↓Speed of LV relaxation with age, even in
the absence of cardiovascular disease dt:
 ↓levels or activity of the sarcoplasmic
reticulum calcium ATP-ase pump (SERCA) .
 ↑levels or activity of phospholamban (the
naturally occurring SERCA-inhibitory protein).
(Garcia, 2000)

7. ↑ LV stiffness with age dt:
↑ collagen cross-linking, ↑ connective
tissue matrix
 ↑smooth muscle content (myocyte
hypertrophy) to compansate for
apoptosis
 loss of elastic fibers
(Garcia, 2000)

9.  Diabetes mellitus can affect cardiac
structure and function in the absence
of hypertension and coronary artery
disease, a condition called diabetic
cardiomyopathy.
 Diastolic dysfunction has been
described as an early sign of this
diabetic cardiomyopthy preceding the
systolic dysfunction.
(Boudina and Abel, 2007)

10. The pathogenesis of diabetic cardiomyopathy:
 Several hypotheses have been proposed:
1- Advanced glycation:
 Of interstitial proteins such as collagen, which
results in myocardial stiffness.
 Of SERCA protein lead to decreased its
activity and prolonged cardiac relaxation
(Hayat et al., 2004)
 2-Endothelial dysfunction

11.  3-Activation of the Renin-Angiotensin-
aldosterone System: (RAAS)
 oxidative damage
 cardiomyocyte and endothelial cell apoptosis.
(Boudina and Abel, 2007)
 4- Increased Oxidative Stress:
hyperglycemia result in excess formation of mitochondrial
reactive oxygen spieces (ROS)
 (NO) level
 myocardial inflammation with myocardial
collagen deposition and fibrosis.
(Young et al., 2002)

12.  5-Autonomic dysfunction
 6-Mitochondrial Dysfunction
 oxidative phosphorylation capacity.
  ATP production.
 7-Inflammatory dysfunction
 expression of nuclear factor kB triggers for
a cascade of pro-inflammatory cytokines
which induce collagen synthesis and fibrosis.
(Boudina and Abel, 2007)

13.  8-Altered Substrate Metabolism
(Metabolic Cardiomyopathy):
 glucose and lactate metabolism and fatty
acid (FA) metabolism .
 FA uptake > oxidation rates in the heart →lipid
accumulation in the myocardium that may
promote lipotoxicity.
 Lipid intermediates such as ceramide promote
apoptosis of cardiomyocytes.
(Boudina and Abel, 2007)

14. Diagnosis of Diastolic heart failure
Is based on three criteria:
 Clinical features of heart failure, particularly left
heart failure;
 A normal ejection fraction (over 50%);
 Evidence of abnormal left ventricular relaxation,
filling, diastolic distensibility or diastolic stiffness.

15. Assessment of Diastolic function
 1-Cardiac catheterisation with simultaneous
pressure and volume measurements
(invasive).
 2-Isovolumic relaxation time (IVRT) A normal
IVRT is about 70±12 ms, about 10ms longer
in those over forty If it's prolonged, it
indicates poor myocardial relaxation.
 3-Transmitral inflow (E/A; E wave
deceleration)
 4-pulmonary venous inflow (atrial flow
reversal) Pulmonary vein Doppler
(Garcia, 2000)
 5-Tissue Doppler imaging
(Satpathy and Mishra,2006)

16. Patterns of Left Ventricular Diastolic Filling
(Aurigemma and Gaash,2004)

17. Management

18. Prevention
 Primary prevention of diastolic heart failure
includes smoking cessation and aggressive
control of hypertension, hypercholesterolemia,
and coronary artery disease. Lifestyle
modifications such as weight loss, smoking
cessation, dietary changes, limiting alcohol
intake, and exercise are equally effective in
preventing diastolic and systolic heart failure.
(Satpathy and Mishra,2006)

19. Management
 The goals of treating diastolic dysfunction :
 normalizing blood pressure.
 promoting regression of left ventricular
hypertrophy.
 preventing tachycardia.
 maintaining atrial contraction
.(Zile and Brustaert, 2002)

20.  Diuretics may improve dyspnea (Watch for
excessive preload reduction, stroke
volume)
 Nitrates Treat and prevent myocardial
ischemia.
.(Zile and Brustaert, 2002)

21. Calcium channel blockers
 Decrease cytoplasmic calcium concentration
and allow myocardial relaxation.
 Reduce blood pressure.
 Reducing myocardial ischemia.
 Regression of left ventricular hypertrophy.
 Slowing the heart rate.
.(Zile and Brustaert, 2002)

22. Beta blockers
 Slowing heart rate .
 Reducing blood pressure
 Reduce myocardial ischemia
 Promoting regression of left ventricular
hypertrophy.
 Antagonizing the excessive adrenergic
stimulation during heart failure.
 Beta blockers have been independently
associated with improved survival in patients
with diastolic heart failure
.(Zile and Brustaert, 2002)

23. Angiotensin converting enzyme (ACE)
inhibitors, Angiotensin (AT) receptor
antagonists, and Aldosterone
antagonists
 Block neurohormonal activation.
 Promote regression of hypertrophy and
prevent myocardial fibrosis.
 Reduce the congestive state.
.(Zile and Brustaert, 2002)

24. Maintain atrial contraction
 Cardioversion of atrial fibrillation.
 Sequential atrioventricular pacing.
 Beta-blockers.
 Calcium-channel blockers.
 Radiofrequency ablation modification
ofatrioventricular node and pacing.
(Aurigemma and Gaash,2004)

25. Digoxin
 Positive inotropic agents (such as digoxin)
are generally not recommended in the
treatment of patients with isolated diastolic
HF, because left ventricular ejection fraction
is preserved.
 Digoxin had no effect on all-cause or cause
specific mortality or CV hospitalizations.
(Aurigemma and Gaash,2004)

26. Alagebrium chloride
 Alagebrium chloride is known to reduce the
pathological condition through breaking AGE
cross-links. However, there has been little
assessment regarding the impact of alagebrium
on AGE-dependent signaling or restoring
structural physiology of human heart.
(Seo et al.,2008)

27. Future consideration
 There is ongoing clinical trial SERCA Gene
Therapy Trial This study is not yet open for
participant recruitment.

28. Summary
 Diastolic Dysfunction is common in elderly
diabetic patients.
 Diastolic Dysfunction is multifactorial.
 Non invasive imaging techniques can be
used for diagnosis.
 At this time, further studies are needed to
determine optimal treatment strategies

29. THANK YOU