Main stay of pathogesis of HCM is due to its

mutation in the sarcomer protein structure causes

the change in structural protein sarcomere which
leads to increase in the muscle cell size [13].Due to
these mutations cadiac muscle muscles undergoes
very huge diarrangment of large muscle cells and
leading to cause fibrosis in structural components of
cardiac muscle cell causing left ventriculat
hypertrophy and increase in interventricular
septum thickness [14]. On histopathological
examination arrangement of cardiomyocytes are in
irregular arrangemt and there is accumulation of
extracellular connective tissue leading to fibrosis and
there nuclei is lost its normal structure [15].
These changes manifests obstruction to outflow
tract during systolic stage (contraction stage) of
cardiac cycle which increases the Left ventricular
end systolic volume [figure 1] ,increase in thickness
of the left ventricular wall progress to dysfunction
in diastole(relaxing stage),and increase in thickness
may also cause the increase in need of blood supply
if not accomapained may cause ischemia of the
tissue,and valves are moved anteriorly leading to
mitral regurgitation [16].
FIGURE 2
Increase in thickness of left ventricular wall and
interventricular septum causes the obstruction of
Aorta,causes increase in left ventricular diastolic
volume and pressure,because of movement of mitral
valve anteriorly cause the mitral regurgitation.
The incidence of atrail fibrillation is increases in
patients with HOCM ,the main reason is changes in
left ventricular thickness leading to increase in left
atrium promotes the abnormalities in
electricalcondiction in left atrial contraction [17].
 MECHANISMS CASUING FOR ECTOPIC ATRAIL
FIBRILLATION
There are few machanims that leads to change in normal
automcity of cardiac muscle cell and causing Atrial
fibrillation.

Action potential of atrial muscle cells are maintained by

inward rectifier K+ current and pacemaker current
(If),through these channels atomicity is attained[18].
The resting action potential is stabilized due to high
flow of K+ ions through respective channel, although
there is high pacemaker current but inward rectifier
K+ current is much larger than this and maintaining
the stable automacity moreover unbalance in this
mainly cause of increased automcity by decrease in
K+ current and increase in pacemaker current [18].

Early afterdepolarizations is caused mainly by

prolongation of actinpotential duraration due to
allowing of L-type Ca2+ current (ICaL) to recover from
inactivation causing depolarizing inward movement
of Ca2+ ions.These changes that take place in atrila
muscle cell is main reason for the increase in
prevalence of atrail fibrillation in congenital long-QT
syndrome patients[19].

Delayed afterdepolarizations due to abnoarmal

release of calcium Ca2+ from sarcoplasmic reticulum
stores during diastole, Specialized sarcoplasmic
reticulum Ca2+ channels are called ryanodine
receptors [RyRs].This abnormal release is due to
response to Ca2+ in the transmembrane. RyRs are
closed during diastole but opened due to channel
abnormality or overlead of calcium in the
sarcoplasmic reticulum.so there is an Na+-
Ca2+ exchanger where one Ca2+ released is
exchanged with 3 extracellular Na+ leading to net
depolarizing inward positive-ion movement,These
changes leads to delayed afterdepolarizations[20].
13 Marian AJ, Braunwald E. Hypertrophic
Cardiomyopathy: Genetics, Pathogenesis, Clinical
Manifestations, Diagnosis, and Therapy. Circ Res.
2017 Sep 15;121(7):749-770. doi:
10.1161/CIRCRESAHA.117.311059. PMID:
28912181; PMCID: PMC5654557.

14 Brigden W. Hypertrophic cardiomyopathy. Br

Heart J. 1987 Oct;58(4):299-302. doi:
10.1136/hrt.58.4.299. PMID: 3314948; PMCID:
PMC1277258.

15 Varnava AM, Elliott PM, Mahon N, Davies MJ,

McKenna WJ. Relation between myocyte disarray
and outcome in hypertrophic cardiomyopathy. Am J
Cardiol. 2001 Aug 1;88(3):275-9. doi: 10.1016/s0002-
9149(01)01640-x. PMID: 11472707.

16 Medical Masterclass contributors, Firth J.

Cardiology: hypertrophic cardiomyopathy. Clin Med
(Lond). 2019 Jan;19(1):61-63. doi:
10.7861/clinmedicine.19-1-61. PMID: 30651247;
PMCID: PMC6399630.
17 Paur H, Wright PT, Sikkel MB, Tranter MH,
Mansfield C, O'gara P, Stuckey DJ, Nikolaev
VO, Diakonov I, Pannell L, Gong H. High levels
of circulating epinephrine trigger apical
cardiodepression in a β2-adrenergic
receptor/Gi–dependent manner: A new model
of Takotsubo cardiomyopathy. Circulation. 2012
Aug 7;126(6):697-706.
18 Stillitano F, Lonardo G, Zicha S, Varro A, Cerbai
E, Mugelli A, Nattel S. Molecular basis of funny
current (If) in normal and failing human heart.
Journal of molecular and cellular cardiology. 2008
Aug 1;45(2):289-99.

19 Johnson JN, Tester DJ, Perry J, Salisbury BA,

Reed CR, Ackerman MJ. Prevalence of early-onset
atrial fibrillation in congenital long QT syndrome.
Heart Rhythm. 2008 May 1;5(5):704-9.
20 Yeh YH, Wakili R, Qi XY, Chartier D, Boknik P,
Kääb S, Ravens U, Coutu P, Dobrev D, Nattel S.
Calcium-handling abnormalities underlying atrial
arrhythmogenesis and contractile dysfunction in
dogs with congestive heart failure. Circulation:
Arrhythmia and Electrophysiology. 2008 Jun
1;1(2):93-102.