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Cardiac
Hypertrophy!
PHYS30001 Cardiovascular Health !
Genes & Hormones!
Professor Stephen Harrap!

Cardiac hypertrophy!
Definition!
Normal

growth!
Growth stimuli!
Characteristics of hypertrophy!
Consequences of hypertrophy!

Definition!
enlargement

of the heart!

global!
left

ventricular!
right ventricular!

Normal growth!
Timing!
Characteristics!
Controls!

Normal growth!
Timing!
parallels

body growth!
doubles in size after 6 months!
triples in size after 1 year!

Normal growth!
Characteristics

- macroscopic!

from

ovoid to spheroid in shape!

greater change in left than right ventricle!
greater wall thickening!
greater increase in ventricular capacity!

RV: 2 to 20 ml!
LV: 2 to 40 ml!

Normal growth!
Characteristics

- microscopic!

myocardial

cell division (hyperplasia)

ceases after first few months!
further growth through hypertrophy!
increased fibre diameter!

RV: 10 to 16 m!
LV: 10 to 20m!

increased

proportion of fibroendothelial

cells!
from 1:1 to 2.5:1!

Normal growth!
Controls!
number

of cells!
hypothalamic-pituitary axis!
growth hormone/IGF!
thyroxine!

Normal growth!
Correlates!
body

size (esp. lean body mass)!

blood pressure!
angiotensin II!
catecholamines!
family history!

Left ventricular mass (g) in healthy young adults!

20

mean = 159 g

10

0
60

100

140

180

220

260

300

340

Growth determinants!
extrinsic!
hemodynamic!

stroke volume!
systolic wave form!
non-hemodynamic!

hormones!
neural!
intrinsic!
genetic!
autocrine,

paracrine!

Heart size correlation between

relatives!

MZ twins
DZ twins
Sibs
Cousins
Spouses

!0.90!
!0.33!
!0.17!
!0.07!
!0.05!

Causes of hypertrophy!
myocardial

infarction!
hypertension!
valve disease!
obesity!
unknown!

Phases of cardiac hypertrophy!

development!
compensated!
decompensated
a

spectrum!

(failure)!

Development of hypertrophy!
increased

work!

preload!
afterload!

increased

strain on !

ventricular

wall!
individual muscle cells!

Patterns of hypertrophy!
normal

concentric

eccentric

pressure
overload

volume
overload

Development of hypertrophy!
cellular

response!

increased

myocardial cell size (> 20 m diam)!

increased number of fibroendothelial cell
number!
especially around epicardial vessels!
increased

interstitial matrix!

Development of hypertrophy!
subcellular

response!

regression

to fetal patterns of gene

expression!
more mitochondria (more energy)!
extra myofibrils (contractile elements)!
more sarcoplasmic reticulum (excitation/
contraction coupling)!
switch from low- to high-ATPase myosin!

Compensated hypertrophy!
normalisation

of strain on individual
sarcomeres and cells!
normalisation of workrate:mass ratio!

Compensated hypertrophy!
normal

cardiac output but!

myocardial cells !
develop

less tension at a given length (less

interactions between actin and myosin)!
develop tension more slowly (reduced
ability of actin to activate myosin ATPase
activity)!

Decompensated hypertrophy!
falling

workrate:mass ratio!
symptomatic deterioration!
heart failure!
death!

Cardiac hypertrophy and

cardiovascular risk!
after

age, LV hypertrophy is the single

most important risk factor for
cardiovascular death!

Consequences of hypertrophy!
greater

risk of cardiovascular death!

underlying

disease!
electrical instability!