E u
T h r m t
G
Andrea
Supplement Epidemiolo under 35 ye
The causes o higher in ma results suppo males and fe the expressiv
Genetic C S
a Mazzanti*
* Mo
§ D
tary Figure ogy of Sudde
ears.
of SCD were ales than in f ort the conce emales, it is
vity of IADs
Causes of Suppleme
*§, MD, Ric
olecular Cardi Department o
e 1.
en Cardiac
e largely com females (inc ept that, whi likely that o s, including
f Sudden entary in
ccardo Mar
iology, IRCCS of Molecular M
Death (SCD
mparable in idence rate r ile the geneti other environ the predispo
n Cardiac nformatio
agna, MD*,
S S. Maugeri F Medicine, Univ
D) between
both gender ratio 2.0, p <
ic determina nmental, beh osition to SC
c Death i on docum
, and Silvia
Foundation, P versity of Pavi
2000-2009 i
s, but the rat
< 0.01), indep ants of IADs havioral and CD, in males.
in the Yo ment
G. Priori, M
Pavia, Italy ia, Pavia, Italy
in Denmark
te of SCD w pendent of a s are equally hormonal fa .
oung
MD, PhD*§
y
k in individu
was significan age. These
prevalent in actors increa
§
uals
ntly n
se
Women are represented in red, men in blue. SADS: Sudden arrhythmic death syndrome (unexplained after autopsy), CAD: coronary artery disease, ARVC: Arrhythmogenic right ventricular cardiomyopathy, CM: cardiomyopathy, Cor Art: coronary arteries.
From: Winkel BG, Risgaard B, Bjune T et al. Gender differences in sudden cardiac death in the young-a nationwide study. BMC Cardiovasc Disord 2017;17:19.
Supplementary Figure 2.
High homology between the Ro52 protein and HERG channels can be the cause of QTc prolongation of autoimmune origin.
Panel A. Relevant homology between Ro52 protein and HERG channel linear structure at the pore region.
Panel B. The secondary structure of a single HERG channel α1 subunit. The pore‐forming extracellular loop is located between S5 and S6. Black and blue circles represent similar and identical amino acids between Ro52 protein and HERG channel.
Panel C, Top view of the tetrameric HERG channel.
From: Fabris F, Yue Y, Qu Y et al. Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea-pigs. J Physiol 2016;594:6175-6187.
Supplementary Figure 3.
Truncating FLNC Mutations are associated to Arrhythmogenic Cardiomyopathy.
Participation in strenuous exercise after the diagnosis of ARVC
Truncating FLNC mutations can alter the sarcomere adhesion to the cytoplasmic membrane, weakening the attachment of myocytes. The consequence is a particular form of cardiomyopathy characterized mainly by left ventricular dilation and systolic dysfunction, myocardial fibrosis predominantly affecting the left ventricle, and a high burden of ventricular arrhythmias that leads to sudden cardiac death. From: Ortiz-Genga MF, Cuenca S, Dal Ferro M et al. Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies. J Am Coll Cardiol 2016; 68:2440-2451.
Supplementary Figure 4.
Kaplan-Meier estimate of cumulative survival free from the first life-threatening arrhythmic event (LAE) during follow-up with patients stratified on the participation in strenuous exercise after the diagnosis of ARVC
Participation in strenuous exercise after the diagnosis of ARVC was independently associated with a three fold increased risk of experiencing a first LAE at follow up (Hazard Ratio 2.98; p=0.028).
This finding is particularly important, regarding a modifiable risk factor, it gives the rationale to modify the life style of patients with a diagnosis of ARVC, which should avoid the participation in
competitive sports, according to a Class I c indication of the most recent guidelines.
From: Mazzanti A, Ng K, Faragli A et al. Arrhythmogenic Right Ventricular Cardiomyopathy:
Clinical Course and Predictors of Arrhythmic Risk. J Am Coll Cardiol 2016;68:2540-2550.
