Pathophysiology

Myocardiocyte

The cardiac myocyte is the major cell involved in remodeling. Fibroblasts, collagen, the interstitium, and
the coronary vessels to a lesser extent, also play a role. A common scenario for remodeling is after
myocardial infarction. There is myocardial necrosis (cell death) and disproportionate thinning of the
heart. This thin, weakened area is unable to withstand the pressure and volume load on the heart in the
same manner as the other healthy tissue. As a result, there is dilatation of the chamber arising from the
infarct region. The initial remodeling phase after a myocardial infarction results in repair of the necrotic
area and myocardial scarring that may, to some extent, be considered beneficial since there is an
improvement in or maintenance of LV function and cardiac output. Over time, however, as the heart
undergoes ongoing remodeling, it becomes less elliptical and more spherical. Ventricular mass and
volume increase, which together adversely affect cardiac function. Eventually, diastolic function, or the
heart's ability to relax between contractions may become impaired, further causing decline.[7]

After a myocardial infarction (MI), cardiac myocyte death can be triggered by necrosis, apoptosis, or
autophagy, leading to thinning of the cardiac wall.[8] The surviving cardiac myocytes either arrange in
parallel or in series to each other, contributing to ventricular dilatation or ventricular hypertrophy,
depending on the loading stress on the ventricular wall.[7] Besides, reduced expression of V1 mysoin and
L-type calcium channels on cardiac myocytes are also thought to cause cardiac remodelling. Under
normal body conditions, fatty acid accounts for 60 to 90% of the energy supply of the heart. Post MI, as
fatty acid oxidation decreases, it leads to reduced energy supply for the cardiac myocytes, accumulation
of fatty acids to toxic levels, and dysfunction of mitochondria. These consequences also led to the
increase in oxidative stress on the heart, causing the proliferation of fibroblasts, activation of
metalloproteinases, and induction of apoptosis, which would be explained below. Besides, inflammatory
immune response after MI also contributes to the above changes.[8]

Besides, the cardiac interstitium which consisted of largely Type I and Type III collagen fibres are also
involved in cardiac remodeling. Cardiac collagen is synthesized by fibroblasts and degraded by
metalloproteinases.[7] Fibroblasts are activated post MI, leading to increased collagen synthesis and
fibrosis of the heart.[8] Increase expression of MMP1 and MMP9 led to degradation of collagen fibres,
and subsequently dilatation of the heart.[7] Several signal pathways such as Angiotensin II, Transforming
growth factor beta (TGF-beta), and Endothelin 1 are known to trigger synthesis and degradation of
collagen fibres in the heart.[8]

Other factors such as high blood pressure, activation of sympathetic system which releases norepinephrine,
activation of renin–angiotensin system which releases renin and anti-diuretic hormones are important contributors of
cardiac remodelling. However, atrial natriuretic peptide is thought to be cardio-protective