Page 254 - fbkCardioDiabetes_2017

230 Congestive Heart Failure in Diabetic...!
How it is Different?

Renin Angiotensin Aldosterone system imbalance toward higher relative sympathetic drive .
activation Sympathetic over activity is a common future in DM
DM is associated with the activation of the RAAS and CHF.. In non-diabetic CHF, sympathetic activa-
with consequent over production of angiotensin II, tion occurs in the later CHF stages leading to insulin
which contributes to heart fibrosis by stimulating ex- resistance, where as cardiac autonomic neuropathy
tra cellular matrix component synthesis, apoptosis/ is a central determinant of the diabetes induced mi-
proliferation, vascular inflammation and oxidative crovascular complication worsening metabolic and
damage. functional alteration in diabetic cardiomyopathy.. The
subsequent progression to CHF in turn, increases
Oxidative, Nitrosative and Nitrative stress. sympathetic activity. Increased cardiac sympathetic
activity, as already discussed, increases lipolysis,
Hyperglycemia –induced pathway activation even- FFA overflow influencing myocardial substrate utili-
tually results in the production of oxygen- derived zation,Mitochondrial uncoupling and oxidative stress
oxidants from both mitochondrial and non-mitochon- with consequent cardiac dysfunction, Cardiac auto-
drial sources.
nomic neuropathy is also associated to a depressed
A chronic increase in oxidative stress has several baroreflex function leading to impaired regulation of
harmful effect on the CV system by directly dam- heart rate variability, stroke volume and blood pres-
aging proteins and DNA, by interfering with nitric sure that have been associated with both systolic and
oxide production and by a modulation of intracellu- diastolic dysfunction., Patients with severe cardiac
lar, signaling pathways and proteins involved in the autonomic neuropathy may have distal sympathetic
stimulated production of reactive oxygen species. Mi- denervation associated with proximal ventricular is-
tochondrial derived- reactive oxygen species appear lands of hyperinnervation that result in myocardial
to play the most crucial role as they can interact with regions that are unstable electrically. In the Action
nitric oxide to form peroxynitrite species which at- to Control Cardiovascular Risk in Diabetes (ACCORD)
tract various biomolecules leading (among other pro- trial, in which cardiac autonomic neuropathy was
cesses) to the production of a modified amino acid, strongly associated with all cause and CV disease
nitrotyrosine, that can disrupt endothielial nitric oxide mortality independent of baseline CVD, DM duration,
synthase activity ultimately reducing nitric oxide bio- multiple traditional CV risk factors and medications .
availability and resulting in endothelial dysfunction.
CLINICAL PHENOTYPES OF DIABETIC
Disease of Small Cardiac Vessels HEART FAILURE
Hyperglycemia is known to induce microangiopa- Diastolic dysfunction
thy, mainly through AGE formation characterized
by thickening of the capillary basement membranc The most frequent and earliest functional abnormal-
and formation of micoaneurysms .These structur- ity in the diabetic heart is impaired diastolic compli-
al alterations cause functional modification such ance, setting the stage for CHF with normal EF.(74).
as impaired nitric oxide production and permeabili- Although this alteration is not unique to DM. It has
ty of the endothelium with consequent endothelial been detected in up to 75% of asymptomatic patient
dysfunction The consequent deficiency in coronary with DM, it has been detected in upto 75% a symp-
blood flow reserve-contributes to loss of contractile tomatic patients with DM. A small study provided in
proteins and myocyte necrosis with reactive focal sight into the phenotypic characteristics
perivascular and interstitial fibrosis,. collagen depo- of patient with DM with LV diastolic dysfunction::40%
sition and hypertrophy of myocardial cells. had diastolic dysfunction, of which two third had im-
paired relaxation and one third pseudo- normaliza-
Cardiac Autonomic Neuropathy tion of mitral inflow on Doppler echocardiography.
Cardiac autonomic neuropathy is a common micro- Of note, patients with diastolic dysfunction were
vascular complication of DM affecting a almost 17% young (mean age 43yrs), normotensive, and under
of the patient with type 1 and 22% of those with type good diabetic control,supporting the hypothesis that
2 DM The severity of hyperglycemia and DM duration diastolic dysfunction. is an early feature in DM. The
are major determinants of cardiac autonomic neurop- development of diastolic dysfunction, found in both
athy, which leads to impaired regulation of CV func- systolic heart failure and HFpEF, though complex
tion .An early manifestation of cardiac autonomic and multifactorial, clearly it is a primary feature of
neuropathy is parasympathetic denervation with an diabetic heart failure.

GCDC 2017