Aritmiile cardiace

n bolile endocrine
Dr. Radu Vtescu

Laboratorul de Pacing i Electrofiziologie Clinic

Clinica de Cardiologie
Spitalul Clinic de Urgen Bucureti

Aritmii boli endocrine

Substrat indus

Agravate/demascate=
substrat pre-existent

Fibroza
HV
Cicatrice

pe cord N
pe cord patologic

IM
miocardite

Anomalii ionice

RV ,,Aritmii - b.endocrine" martie 2016

Tiroida si sistemul cardio-vascular

disf(x) tiroidiene morbi-mortalitate c-v
Gencer et al

Thyroid Dysfunction and Heart Failure

gure. Hazard ratios (HRs) for heart failure (HF) events according to thyroid-stimulating hormone (TSH) levels. Age- and sex-adjust
Gencer B, et al. Circulation 2012
Rs and their 95% confidence intervals (CIs) are represented by squares. Squares to the right of the solid lines indicate increased
HF events. Sizes of data markers are proportional to the inverse of the variance of the HRs.

86 (95% CI, 1.272.72) for TSH of 10.0 to 19.9 mIU/L (P

analyses was 1.46 RV

(95%
CI, 0.94 2.27) compared3
,,Aritmii - b.endocrine" martie 2016

Efecte h-d

c
d

TABLE 1. CHANGES IN CARDIOVASCULAR FUNCTION

ASSOCIATED WITH THYROID DISEASE.*

MEASURE

NORMAL
RANGE

VALUES
IN HYPER-

VALUES
IN HYPO-

THYROIDISM

THYROIDISM

15001700 7001200 21002700

Systemic vascular resistance
(dynseccm5)
Heart rate (beats/min)
7284
88130
6080
Ejection fraction (%)
5060
>60
60
Cardiac output (liters/min)
4.06.0
>7.0
<4.5
Isovolumic relaxation time (msec)
6080
2540
>80
Blood volume (% of normal value)
100
105.5
84.5
Klein I, Ojamaa J. NEJM 2001
*The values
for patients with hyperthyroidism and those with hypothyroidism are taken from Klein and Levey,6 Graettinger et
al.,7 Mintz et al.,8
RV ,,Aritmii - b.endocrine" martie 2016

a
t
t
c
t
h
n
t
s
i
u
p

Efecte h-d

Klein I, Danzi S. Circulation 2007

RV ,,Aritmii - b.endocrine" martie 2016

Myopathy

TREs as homodimers or, more commonly, as heterodimers

with 1 of 3 isoforms of retinoid X receptor (RXR!, RXR", or
RXR#).16 While bound to T3, TRs induce transcription, and in

Mecanisme i-celulare
359.9

ICD-9 indicates International Classification of Diseases, Ninth Edition.

Klein I, Danzi S. Circulation 2007

Figure 1. T3 effects on the cardiac myocyte. T3 has both genomic and nongenomic effects on the cardiac myocyte. Genomic mechaRV ,,Aritmii
- b.endocrine"
nisms involve T3 binding to TRs, which regulate transcription of specific cardiac genes. Nongenomic mechanisms
include
direct modu-martie 2016

Table 2. Effect of Thyroid Hormone on Cardiac Gene

Expression
Positively Regulated

Negatively Regulated

"-Myosin heavy chain

!-Myosin heavy chain

Sarcoplasmic reticulum Ca2!-ATPase

Na!/K!-ATPase

!1-Adrenergic receptor
Atrial natriuretic hormone

Phospholamban
Adenylyl cyclase catalytic subunits
Thyroid hormone receptor "1
Na!/Ca2! exchanger

Voltage-gated potassium channels

(Kv1.5, Kv4.2, Kv4.3)
Non-genomic (direct) T3-mediated effects (heart and VMC):

17 Negatively
the -ion
absence
of (sodium,
T3 theypotassium,
repress transcription.
channels
and calcium)
regulated
cardiac genes such as !-myosin heavy chain and
-actin polymerization
-adenine nucleotide
translocator
(mitochondrial
membrane)
phospholamban
are induced
in 1the
absence of
T3 and repressed in the presence of T3 (Table 2).18 20
Thyroid
hormone effects on the cardiac myocyte are
Klein I, Danzi S. Circulation 2007
intimately associated with cardiac function via regulation of
RV ,,Aritmii - b.endocrine" martie 2016

con
hem

Eff
He

Thy
latu
left
Thy
arte
arte
the
sod
wh
com
In h
out
hyp
opp
7

Aritmii atriale Hypertiroidism

Induse

Agravate/demascate=
substrat pre-existent

tahicardia sinusal*
ESA
TA nesustinut si polimorf
fibrilaia atrial$

macro-reintrri

* n lipsa altor cauze de TS

-anemie
-ICC
-TEP
-sevraj, etc

TRNAV (,,intranodal)
TRAV (cale accesorie)
Flutter A tipic
Flutter A pericicatr.

focale (tahicardii atriale)

automatism aN
micro-reintrari
activitate declansat

apariia sau agravarea poate fi primul semn la

varstnici; la tineri aparitia de novo niciodat fr
alte semne de hipertiroidism
$

RV ,,Aritmii - b.endocrine" martie 2016

afterdepolarization (DAD) in a pulmonary vein beating cardiomyoc

During electrical stimuli of 0.1 Hz, there were two DAD after comp
repolarization. Arrows indicate the occurrence of DAD.

Aritmogeneza in hipertiroidism
(n # 34)
Atrial (n # 16)

64 ! 1 98 ! 4 120 ! 15

240 ! 14

Values are means in

! SE.the
*p " 0.05;
p " 0.005; p " 0.001and
significantly
different
Table 1. The AP Parameters
Hyperthyroid
Control
from control cells by Tukey test.
APAtrial
# action potential;
APA # amplitude of AP; APD and APD # action
PV Cardiomyocytes or
Myocytes
potential duration at 50% and 90% repolarization, respectively; MDP # maximal

AP occurred after complete repolarization, which was co

sistent with DAD.
PV cardiomyocytes without spontaneous activities.
diastolic potential; PV # pulmonary vein.
JACC Vol. 39, No. 2, 2002
Figure 2. Effects of thyroid hormone on the occurrence of delayed
MDP
APA
APD50January 16, 2002:36672
APD90 the example shown in Figure 3, the AP duration
Thyroid (APD
Hormo
afterdepolarization (DAD) in a pulmonary vein beating cardiomyocyte.
and
APD
)
of
the
hyperthyroid
PV
cardiomyocytes
w
spontaneous
activities,
and
34
cells
did
not
have
spontane90
(!mV) (mV)
(ms)
(ms)
During electrical stimuli of 0.1 Hz, there were two DAD after complete
repolarization. Arrows indicate the occurrence of DAD.
shorter than that of control PV cardiomyocytes (Table 1).
ous activities. The electrical capacitance was similar between
the atrial cells, there was shorter AP duration (APD50)
AP occurred after complete Hyperthyroid
repolarization, whichcardiomyocytes
was con- the hyperthyroid and control PV beating cardiomyocytes
hyperthyroid
cardiomyocytes than there was in cont
(168 ! 28 pF vs. 143 ! 24 pF), nonbeating cardiomyocytes
sistent with DAD.
PV
beating
cells
(n
#
26)
55
!
1
93
!
2
155
!
12
278
!
10
cardiomyocytes.
PV cardiomyocytes without spontaneous activities. As (136 ! 16 pF vs. 125 ! 8 pF) and atrial cells (155 ! 24 pF
nine
PV
Nonbeating
cells50 vs. 149 !62
!No.22, 2002118 ! 20 286 ! 21 During electrical stimulation, Chen
28 !
pF).2 JACC94
the example shown in Figure
3, the
AP duration (APD
Vol. 39,
et al.(45%)
369 of the
16,
2002:36672
Thyroid
Hormone
on
PV
Cardiomyocytes
and APD90) of the hyperthyroid PV cardiomyocytes were PV cardiomyocytesJanuary
hyperthyroid
non-beating
PV
cardiomyocytes
with
spontaneous
activities. The hyJACC
Vol. 39,
No. 2, 2002
Chen et al.
369have DA
(n # 20)
January 16, 2002:36672
Thyroid
Hormone
on
PV Cardiomyocytes
shorter than that of control PV cardiomyocytes (Table 1). In perthyroid PV beating
which
was
higher
than
the
incidence
of
DAD
in control P
cardiomyocytes had a faster beating
Atrial
# 14)
!
2
96
!
1
52
!
14*
176
!
18
the atrial cells, there was shorter
AP (n
duration
(APD50) in rate than 62
the control PV beating cardiomyocytes (1.82 !
hyperthyroid cardiomyocytes than there was in control
Control
cardiomyocytes
0.13 Hz vs. 1.03 ! 0.15 Hz, p " 0.005). The AP duration
cardiomyocytes.
(APD50, APD
PV16
beating383
cardioPV beating
cells
(n 20
# 36)
57 !90)1of the
92 hyperthyroid
! 3 220 !
! 28
During electrical stimulation,
nine (45%)
of the
Figure 2. Effects of thyroid hormo
hyperthyroid non-beating PV cardiomyocytes have DAD, myocytes was shorter than that of control PV beating
PV
Nonbeating
cells
63
!
1
92
!
2
231
!
18
374
!
22
afterdepolarization (DAD) in a pulm
which was higher than the incidence of DAD in control PV cardiomyocytes.
During electrical stimulation or in spontaneously beating
(n # 34)
During electrical stimuli of 0.1 Hz, th
Chen et al.
JACC Vol. 39,
2, 2002
myocytes, 64
12 !
(46%)
of
the
26 hyperthyroid
PVNo.
beating
Atrial
(n
#
16)
1
98
!
4
120
!
15
240
!
14
repolarization. Arrows indicate the oc
Thyroid Hormone on PV Cardiomyocytes
January
cardiomyocytes had EAD, and 24 (92%)
of 16,
the2002:36672
hyperthyPV beating
had delayed
afterdepolarValues are means ! SE. *proid
" 0.05;
p " cardiomyocytes
0.005; p " 0.001
significantly
different
1. The AP Parameters in the Hyperthyroid and Control
ization
(DAD).
In
contrast,
none
of
the
36
control PV
from control cells by Tukey test.
ardiomyocytes or Atrial Myocytes
beating cardiomyocytes had EAD (p " 0.0001 vs. hyperAP #APD
action potential;
APA
# amplitude of AP; APD50 and APD90 # action
MDP
APA
APD90
thyroid cells), and only two (6%) of the
cells had DAD (p "
50
potential
duration
at
50%
and
90%
repolarization, respectively; MDP # maximal
(!mV) (mV)
(ms)
(ms)
0.0001 vs. hyperthyroid cells). Figure 1 shows an example of
diastolic potential; PV # pulmonary
vein. PV beating cardiomyocytes with the ochyroid cardiomyocytes
the hyperthyroid
ting cells (n # 26)
55 ! 1 93 ! 2 155 ! 12 278 ! 10
currence of EAD during spontaneous beating. Figure 2
nbeating cells
62 ! 2 94 ! 2 118 ! 20 286 ! 21
shows the other example of the hyperthyroid PV cardiomy20)
90
ocytes with DAD. During electrical stimuli, the triggered
n # 14)
62 ! 2 96 ! 1 52 ! 14* 176 ! 18
50

90

AP occurred after complete rep

sistent with DAD.
PV cardiomyocytes without
the example shown in Figure
and APD ) of the hyperthyro
spontaneous activities, and 34 cells did not have spontanel cardiomyocytes
shorter than that of control PV
ous activities. The electrical capacitance was similar between
ting cells (n # 36)
57 ! 1 92 ! 3 220 ! 16 383 ! 28
Figure 2. Effects of thyroid hormone on the occurrence of delayed
nbeating cells
63 ! 1 the
92 ! 2 hyperthyroid
231 ! 18 374 ! 22
the atrial cells, there was shor
and
control(DAD)
PVin a beating
afterdepolarization
pulmonary vein cardiomyocytes
beating cardiomyocyte.
34)
During electrical stimuli of 0.1 Hz, there were two DAD after complete
n # 16)
64 ! 1 (168
98 ! 4 120
15 pF
240 ! vs.
14 143
hyperthyroid cardiomyocytes
repolarization.
the occurrence of cardiomyocytes
DAD.
!!28
! 24Arrows
pF),indicate
nonbeating
re means ! SE. *p " 0.05; p " 0.005; p " 0.001 significantly different
AP occurred
after and
complete
repolarization,
which was
(136 ! 16 pF vs. 125
! 8 pF)
atrial
cells (155
! con24 pF has thecardiomyocytes.
ntrol cells by Tukey test.
non-beating cardiomyocytes (one in 34 cells, 3%, p !
properties of rapid activation kinetics and increased
action potential; APA # amplitude of AP; APD and APD # action
sistent with DAD. 0.005).
The
incidence
of
EAD
in
hyperthyroid
PV nonprogressively
in amplitude
with increasing
non-beating cardiomyocytes (one in 34 cells, 3%,
p !
has the properties
of rapid activation
kineticsdepolarization
and increased
duration at 50% and 90% repolarization,
respectively;
MDP
#
maximal
During
electrical
stimulatio
vs. 149 ! 28 pF). PV cardiomyocytesbeating
cardiomyocytes
(one
in 20inactivities.
cells,
5%) was As
similar
to
steps.
The depolarizing
stepswith
also increasing
induced a slowly
activatwithout
spontaneous
0.005).
The incidence
of
EAD
hyperthyroid
PV nonprogressively
in amplitude
depolarization
potential; PV # pulmonary vein.
that
in cardiomyocytes
control PV non-beating
cardiomyocytes
(0 in 34
ing
non-inactivating
steady
state
outward
current
similar
to
beating
(one
in
20
cells,
5%)
was
similar
to
steps.
The
depolarizing
steps
also
induced
a
slowly
activatthe
example
shown
in
Figure
3,
the
AP
duration
(APD
hyperthyroid
non-beating
PV
50hyPV cardiomyocytes with spontaneous
activities.
cells,
0%).
In atrial
cells,
the incidence
of The
DAD (one
the
of steady
delayedstate
rectifier
outward
current.
The
that in
control
PV
non-beating
cardiomyocytes
(0 in 14
34
ing characteristics
non-inactivating
outward
current
similar
to
and APD90) of thecells,
hyperthyroid
PV
cardiomyocytes
were
aneous activities, and 34 cells did not have spontane7%) or
(0 in the
14 incidence
cells, 0%)ofwas
similar
density
of the steadyofstate
outward
current
fromThe
the
0%).
In EAD
atrial cells,
DAD
(onetointhe
14Figure
the3.characteristics
delayed
rectifier
current.
Effects
of thyroid
hormone
on outward
the(measured
action
potential
(AP)
durat
which
was
than
the
inci
perthyroid
beating
cardiomyocytes
had
acells,cells,
faster
beating
incidence
of
inin
1614
0%)0%)
or EAD
(0 inIn
16tocells,
at the
endoutward
of 1higher
s depolarization
from "40
mV
shorter
that
control
PV
cardiomyocytes
(Table
1).
cells, 7%)
orDAD
EAD
similar
theof a outward
density
ofcurrent
thevein
steady
state
current
(measured
from
the electricall
tivities. The electrical capacitance
was similar PV
between
Figure 1.than
Effects
of of
thyroid
hormone
on(0(0the
occurrence
ofwas
early
after
pulmonary
(PV)
non-beating
cardiomyocyte
driven
0%)
in
control
atrial
cells.
to
%60
mV)
was
also
greater
in
hyperthyroid
(n
#
20)
than
it
incidence
of
DAD
(0
in
16
cells,
0%)
or
EAD
(0
in
16
cells,
outward
current
at
the
end
of
1
s
depolarization
from
"40
mV
Figure
6. Membrane
a hyperthyroid
(A)There
and a control
pulmonary
(PV) cardiomyocyte.
The io
the
atrial cells,
wasvein
shorter
duration
(APD
) inacurrentsaofrate
depolarization
in a there
pulmonary
beatingAP
cardiomyocyte.
The
cell
of 0.1 Hz.
was a (B)
shorter
AP vein
duration
at 50% repolarizat
yperthyroid and control PV beating cardiomyocytes
50has
of thyroid
hormone
onpotential
ionic
currents
PV
was
in ranging
control
(n also
#!20
32)
PV
beating
cardiomyocytes
(0.78
$
rate
than
the
control
PV
beating
cardiomyocytes
(1.82
of
!40
mVofto!
testand
potentials
from
mVthe
to hyperthyroid
!120
mV. The
inset
shows
0%)(2
control
atrial
cells.
to
mV)
was
greater
in
(n #
20)
thanthere
itthe various
Figure 3. Effects of thyroid hormone
on the action
potential
(AP)Chen
duration
rapid
spontaneous
activity
with
oscillation
plateau
phase
at %60
90%
repolarization
in
hyperthyroid
than
was9incl
Y-C,
et
al.Effects
Jin Hz)
Am
Coll
Cardiol
hyperthyroid
cardiomyocytes
than
there during
was
in control
! 28
pF vs. 143 ! 24 pF), nonbeating
cardiomyocytes
RV
,,Aritmii
- b.endocrine"
martie(A)2016
current-voltage
curves2002
of the two cells.
The
hyperthyroid
and control PV cardiomyocytes
had similar electrical
ca
Figure 4. Membrane currents of a hyperthyroid (A) and a control (B) pulmonary vein (PV) cardiomyocyte. The ionic currents were elicited on
depolarization from "40 mV to %60 mV. The inset shows the various clamp protocols. The hyperthyroid and control PV cardiomyocytes had similar
Figure 4. Membrane currents of a hyperthyroid (A) and a control (B) pulmonary vein (PV) cardiomyocyte. The ionic currents were elicited on
electrical capacitance. C and D show the measured current-voltage curves of the two cells. The overall transient outward (Ito) and the steady state outward
depolarization from "40 mV to %60 mV. The inset shows the various clamp protocols. The hyperthyroid and control PV cardiomyocytes had similar
currents (Ik) were indicated by circles and triangles, respectively.
electrical capacitance. C and D show the measured current-voltage curves of the two cells. The overall transient outward (Ito) and the steady state outward
currents (Ik) were indicated by circles and triangles, respectively.

50

90

of a pulmonary vein (PV) non-beating cardiomyocyte driven electrically at

DEPOLARIZATION-INDUCED
CURRENTS.
cardiomyocytes.
Effects of thyroid
hormone on ionic currents
of PV

0.06
pA/pF
vs. (n
0.58
! 0.05).
was in
control
#$
32)0.04
PV pA/pF,
beating pcardiomyocytes
(0.78 $

Sawin CT, et al. N Engl J Med 1994

RV ,,Aritmii - b.endocrine" martie 2016

10

Antiautonomic Receptor Antibodies in Graves AF

m when introduced as
Clinical, Echocardiographic,
Biochemical
Clinical,
Characteristics
Echocardiographic,
and
of the Patients
and
Table 1
2-Hz pacing train.
Biochemical Characteristics of the Patients
y flow cytometry. PuriAtrial
Normal Sinus
(1:200) with isotonic
Fibrillation
Rhythm
4% bovine serum albu(n ! 17)
(n ! 21)
Age (yrs)
60.9 $ 12.7
45.7 $ 13.1
incubated with Chinese
Male (%)
47.1
42.9
ngth human thyrotropin
Hypertension (%)
70.6
61.9
Antihuman IgG (H!L)
Diabetes mellitus (%)
35.3
23.8
cyanate (BD Bioscience
Coronary artery disease (%)
17.6
9.5
was the secondary antiHeart failure (%)
52.9
23.8
y was measured by flow
Ejection fraction (%)
51.6 $ 16.1
52.4 $ 16.2
en). A human monocloLeft atrium (mm)
42.3 $ 7.8
38.3 $ 7.6
R that stimulates cyclic
E (m/s)
0.83 $ 0.25
0.98 $ 0.37
1312
Stavrakis et al.
-TSHR cells
confirmed
DT (ms) Antibodies in Graves AF 245.2 $ 72.2
242.4 $ 77.9
Antiautonomic Receptor

HR cells were maintained

d with 10% fetal bovine
ia), 100 U/ml penicillin,
gen, Grand Island, New
detached by phosphatethylenediaminetetraacetic
etic acid. Counted (1 "
0 !l of diluted (1:200)
ocking at room temperae collected by centrifugad using pre- and postction in mean fluorescent
nt adsorption. All experand post-adsorbed serum
by enzyme-linked immu-

longation of
potential dur
after a 20-be
p Value
250, 500, 1,0
0.001*
presence of I
1.00
for each paus
0.73
prolonged pa
0.49
action potent
0.64
depolarizatio
0.09
local autonom
0.88
79% of the p
0.15
IgG, respecti
0.17
JACC Vol. 54, No. 14, 2009
of the stimu
0.90
September 29, 2009:130916
significantly
E/E=
5.9 $ 2.5
6.6 $ 2.5
0.50
the left (EV5
Serum thyrotropin (mU/l)
0.075 $ 0.12
0.071 $ 0.18
0.94
longation of the terminal action potential duration (action
Serum free thyroxine (ng/dl)
2.35 $ 1.3
3.08 $ 2.3
0.22
IgG, respect
potential
duration
at 90% of repolarization) was enhanced
afterdepolariz
after
a 20-beat
pacing
DT & deceleration time of mitral E flow velocity; E & early diastolic
velocity
of mitral inflow;
E/E= & train at 6 Hz for pause durations of
stimulationi
ratio between the early diastolic velocity of mitral inflow (E) and250,
that of500,
mitral annulus
1,000,(E=).2,000, and 4,000 ms, respectively,
in the
lol
presence of IgG compared with control subjects (p !(32
0.01nmol
ening,
for$
each
pause
duration).
byand
a lo
sinus rhythm (60.9 $ 12.7 years vs. 45.7
13.1
years,
p % With rapid pacing followed
prolonged
pause,
prolongation of the terminal phase
of the
gered
firing w
0.001). Otherwise, no difference was noted
for the
percentaction
potential
clearly
assumes
the
form
of
an
early
afterDeterminan
age of male sex, presence of hypertension, diabetes mellitus,
depolarization (Figs. 2B and 2C). Triggered firing
withvaria
for 14
coronary artery disease, and congestive heart failure between
local autonomic nerve stimulation was observed inAA
50%!1AR
and an
the 2 groups. Echocardiographic indexes,
including
left
ven79% of the pulmonary sleeve preparations before creased
and afterAA!
tricular ejection fraction, left atrial diameter,
early
diastolic
IgG, respectively (p " NS). The IgG decreased the voltage
effects (perce
velocity of mitral inflow (E), decelerationof
time
mitral Etrain
flow needed to induce triggered
theofstimulus
firing,
related
to the
velocity (DT), and the ratio between the early
diastolic
velocity
significantly moving the stimulus voltage-response curve to
thebefore
copresenc
Functional
Effects
IgG
of mitral inflow and that of mitralStavrakis
annulus
(E/E=)
didofal.
not
the
left
(EV
"Jdiffer
70
# Coll
2 V vs.
96 # 2 V
after and
50
S,With
et
Am
Cardiol
2009
Figure 1 From Patients
Graves Disease and
independent
respectively,
p !
0.001) (Figs. 2D and 2E).
Early
significantly between the 2 groups.Control
SerumIgG,
thyrotropin
and free
Subjects
on Purkinje
Fiber Contractility
RV
,,Aritmii
b.endocrine"
martie
2016
11
interval
afterdepolarization formation and local autonomic
nerve[CI]

Aritmii ventriculare Hipertiroidism

Induse

Agravate/demascate=
substrat pre-existent

NICIUNA!

pe cord N
ESV/TV de tract de ejecie
+/-TV idiopatica VS
(fasciculara)

pe cord patologic
CAVD
CMH
post-IM

RV ,,Aritmii - b.endocrine" martie 2016

12

Hipertiroidism
ICC
secundar tachyCMP
rspuns spectaculos la bB
revers-remodelare
spectaculoas

HTP
usoar (PAPs 30-50 mm Hg)
de debit

RV ,,Aritmii - b.endocrine" martie 2016

13

Klein and Danzi

en
s,
tbe
ed
ed
to

pst
nd

Hipotiroidism
Thyroid Disease and the Heart

1731

Table 4. Cardiovascular Risks Associated With

Hypothyroidism
Impaired cardiac contractility and diastolic function
Increased systemic vascular resistance
Decreased endothelial-derived relaxation factor
Increased serum cholesterol
Increased C-reactive protein
Increased homocysteine

hypertension (diastolic), narrowed pulse pressure, cold intolKlein I, Danzi S. Circulation 2007
erance, and fatigue.10,28 Overt hypothyroidism affects "3%
RV ,,Aritmii - b.endocrine" martie 2016

14

Aritmii - hipotiroidism
Atriale
bradicardie sinusal

Ventriculare
LQT
ESV
TdP (exceptional)

RV ,,Aritmii - b.endocrine" martie 2016

15

Interactiuni c-v -- tiroida

1732

Circulation

October 9, 2007

1.0

20 % & total T3 > 1.2 nmol/L

.8
EF > 20 % & total T3

1.2 nmol/L

EF

1.2 nmol/L

.7
20 % & total T3

P<0.0001

EF

P=0.02

Survival

.9

P=0.002

EF > 20 % & total T3 > 1.2 nmol/L

.6
.
.5
.4

12

18

Follow-up Time (months)

Figure 4. Low T3 syndrome and ejection fraction as predictors of mortality. A low T3 level is a better predictor of all-cause and cardiovascular mortality than is an abnormal left ventricular ejection fraction. EF indicates ejection fraction. Reprinted from Pingitore et al108
with permission of the publisher. Copyright 2005, Elsevier.

atherosclerotic cardiovascular disease more often improve,

rather than worsen, with treatment.

levels.107109 The decrease in serum T3 is proportional to the

severity of the heart disease as assessed by the New York Heart
Klein I, Danzi S. Circulation 2007
Association functional classification.107 The low T3 syndrome is
Subclinical Thyroid Disease
defined as a fall in serum T3 accompanied by normal serum T4
Subclinical hyperthyroidism is characterized by a low or undeRV ,,Aritmiiresults
- b.endocrine"
martie 2016
and TSH levels, and the syndrome
from impaired
hepatic

16

Analogi ai h.tir.
Eprotirome Treatment of Hypercholesterolemia

Placebo

Eprotirome, 25 g

Eprotirome, 50 g

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20
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Eprotirome, 100 g

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12

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Landeson
PW,
et al.Levels
N Engl
J Med
2010 and Triglycerides.
Figure 1. Effects
of Eprotirome
on Serum
of Cholesterol,
Lipoproteins,
RETAKE:
1st
AUTHOR: Ladenson
RV ,,Aritmii - b.endocrine"
Mean changes in levels of serum low-density lipoprotein (LDL) cholesterol (Panel A), apolipoprotein
B (Panel B),martie 2016

17

Coagulare - hipertiroidism
productie fact. coagulare

084

Stuijver et al. Hyperthyroidism and coagulation

metabolism vit K
metabolism ACO

>> pt acenocumarol
<< pt warfarina

StuiverDJF
et al. intervention
Thrombosis
andprothrombin
Haemostasis
2012
Figure 4: Haemostatic parameters for all medium-/high-quality
observational
studies. F1+2,
fragment 1+2; pFN,
plasma fibronectin; cFN, cellulair fibronectin; VWF, von Willebrand factor; Ag, antigen; C, activity; PAP plasmin-antiplasmin
complexes;
t-PA, tissue
type-plasRV ,,Aritmii
- b.endocrine"
martie
2016

18

implantation.
with more severe disease were treated with prednisone.
Finally, multivariate Cox regression analysis showed that
We could not identify enough patients treated with
the use of prednisone remained a predictor of the primary
iopanoic acid to make valid conclusions. Thyroidectomy was
end point after adjusting for confounding variables (hazard
performed relatively late. Higher fT4 levels suggest that
ratio 1.96; 95% confidence interval 1.03 to 3.72).
2354
Conen et al.
patients
with the most severe disease underwent surgery.
Amiodarone-Induced Thyrotoxicosis
Considering the increased event rate, early thyroidectomy
Discussion
may be worthwhile in selected cases because definite cure of
AIT can be achieved rapidly and long-term amiodaronetance of reduced left ventricular fun
The present analysis confirms that medical therapy for AIT
therapy can be continued safely. Surgery is an optionpresence of left ventricular dysf
is challenging. It may take several months before euthyroidindependent predictor of the pr
Duration
and
in Patients
of Follow-Up
Stratified
and According
Incidence to
of Left
the Primary
Ventricular
Composite
FunctionEnd
at Point
the Time
in All
of Patients
AIT Diagnosis
multivariate analysis. This may be
Duration of Follow-Up and Incidence of the Primary Composite End Point in All Patients
Table 5
and in Patients Stratified According to Left Ventricular Function at the Time of AIT Diagnosis
tical power because of the low n
group with reduced left ventricula
All Patients (n ! 84)
Normal EF (n ! 57)
Impaired EF (n ! 26)
p Value
after AIT patients may remain
Duration of follow-up (months)
50 (1778)
50 (1978)
44 (1678)
0.54*
Primary composite end point (%)
47 (56)
28 (49)
19 (73)
0.04 reducing the influence of left ven
Death (%)
16 (19)
8 (14)
8 (31)
0.07 come. This especially may be true
Heart transplantation (%)
3 (4)
1 (2)
2 (8)
0.23 most effective antiarrhythmic dru
Hospitalization for heart failure (%)
13 (16)
8 (14)
5 (19)
0.55 permanently.
Stroke (%)
5 (6)
2 (4)
3 (12)
0.18
Therefore, with regard to
Acute myocardial infarction (%)
3 (4)
2 (4)
1 (4)
1.00 arrhythmia-related events during lo
Hospitalization for arrhythmia management (%)
23 (27)
11 (19)
12 (46)
0.01
tinuation of amiodarone despite th
Atrial fibrillation
7 (8)
5 (9)
2 (8)
be considered as a therapeutic op
2354
Conen et al.
JACC Vol. 49, No. 24, 2007
Ventricular fibrillation/tachycardia
10 (12)
2 (4)
8 (31)
Amiodarone-Induced Thyrotoxicosis
June 19, 2007:23505
analyses suggest that amiodarone
Implantation of defibrillator device
7 (8)
1 (2)
6 (23)
during and after AIT (16,17). H
Pacemaker implantation
7 (8)
4 (7)
3 (12)
tance
of
reduced
left
ventricular
function
(15).
However,
the
Hospitalization for treatment complication
3 (4)
3 (5)
0
0.53 trolled data about continued amiod
with AIT are needed.
presence of left ventricular dysfunction failed to be an
Data are numbers (percentage) or median (interquartile range). *p value is based on a Mann-Whitney U test. p value is based on a chi-square test. p value is based on a Fisher exact test.
Clinical implications. In patien
independent predictor of the primary end point in the
event rate suggests the need for clo
multivariate analysis. This may be related to reduced statistherapy should be carefully selecte
tical power because of the low number of patients in the
Downloaded From: http://content.onlinejacc.org/ on 06/10/2013
thyroid ultrasound and Doppler
group with reduced left ventricular function. Alternatively,
ment
of radioiodine uptake (19),
after AIT patients may remain at high long-term risk,
such
as
interleukin-6 (20) may be
reducing the influence of left ventricular function on outAIT
patients
who may benefit f
come. This especially may be true when amiodarone as the
Early
favorable
response to a sho
most effective antiarrhythmic drug must be discontinued
might
be
another
criterion for fin
permanently.
benefit
from
continuation
of stero
Therefore, with regard to the high incidence of
tion
of
euthyroidism.
Patients
with
arrhythmia-related events during long-term follow-up, conresponse to medical therapy a
tinuation of amiodarone despite the occurrence of AIT may
thyroidectomy.
be considered as a therapeutic option. Some uncontrolled
analyses suggest that amiodarone may be continued safely Because the findings from th
patients with AIT are at risk for co
during and after AIT (16,17). However, prospective conperiod of time, prolonged followtrolled data about continued amiodarone therapy in patients
tion of thyroid function should b
with AIT are needed.
clinicians should look for o
Figure
1
Event-Free
Survival
Clinical
implications.
In
patients
with
AIT,
the
high
Conen D, et al, J Am Coll Cardiol
2008 ticular,
RV ,,Aritmii - b.endocrine"
2016common19co
recurrence,martie
the most

Amiodarona - tiroida

discrete aN ale testelor tiroidiene

hipotiroidismul indicaie de oprire a AA
hipertiroidismul (I sau II) indicaie de oprire a AA

DM - arrhythmias
advGEPs, oxidative stress, polyol
ASC
Accelerated apoptosis, fibrosis, connexin 43 malfunction
ventricular stiffness filling pressure
GPZ deposition
LVH (PPAR- mediated)

O-linked glycation of Ca2+/calmodulin-dependent PK II

sarcolemal release Ca2+ i-cel (Erickson JR et al, Nature 2013)
filling pressure
delayed afterdepolarizations

Cardiac neuropathy:
sympathetic/parasimpathetic & maldistribution
Silent ischemia
QTc
RV ,,Aritmii - b.endocrine" martie 2016

20

Figure 1. Hypothetical involvement of metabolism

in cardiac adaptation. The central dogma for the

To inhibit mitochondrial import of long-chain
fatty acid
adaptation of the myocardium to various stimuli is
(LCFA), mice were injected i.p. with the !
enantiomer
of side of the figure. Activation of
depicted
on the left
etomoxir (25 ng!kg) or vehicle (sterile water) G-protein
daily for 3coupled
weeks.receptors (GPCR), receptor
During this 3-week period, mice were fed either
HF or
control
tyrosine
kinases
(RTK), and integrins in response
chow.
to multiple stimuli result in the activation of numer-

1864

Circulation

ous signaling cascades, such as those employing

calcium
(Ca2!Adult
), protein kinase C (PKC) isoforms,
Isolation of Cardiac Myocytes and Electrophysiologic
Studies.
Ca2!/calmodulin kinase (CaMK),
cardiac ventricular myocytes were isolated,calcineurin,
and whole-cell
mitogen-activated
voltage-clamp recordings were obtained by using
an Axopatchprotein kinases (MAPKs), and
1D patch-clamp amplifier and the PCLAMP 8 phosphatidylinositol
software package 3-kinase (PI3K). The latter
affect transcription and translation, processes
(Axon Instruments, Foster City, CA), as described
(10).forFurther
essential
the chronic adaptation of the heart.
description of these and other methods is found
in Supporting
The current
review hypothesizes that alterations in
which is published as supporting information
on the generate
PNAS essential components
metabolism
AprilText,
16, 2002
web site, www.pnas.org.
involved in this adaptation (right).

cesses such Figure

as transcription,
translation,
stabiliceramide. DAG is an allosteric activator of several PKC
3. Metabolic
adaptationand
and protein
maladaptation
After
a mid-ventricular
of stimuli
As exemplified
inVarious
Figure
2, glucose
is more
than just
ty.3739
of the heart.slice
can result
in rapid
isoforms. Increased DAG levels Histologic
and PKC Analyses.
activity are
ob- harvest,
myocardium
snap-frozen
in an
a cryomold
for sectioning
oracid
alterations
in fatty
and glucose
metabolites
19,33
energy source
for the
heart.
Failure
to adequately
control
served in myocytes isolated from
diabetic was
animals.
preserved in buffered formalin. To detect neutral
frozen
within lipid,
the cardiomyocyte.
These metabolites then
intracellular
glucose
levels
(glucotoxicity)
has
also
been
Chronically activated PKC has been
suggested
to
play
a
role
act as essentialwith
signaling molecules for the adapsections were stained with oil red O and counterstained
34 Ceramide, whose
implicated
in
the
development
of
insulin
resistance
and
in
the
in the development of insulin resistance.
tation
process.
However,
if
the
intensity
of
the
hematoxylin. To detect signs of fibrosis, sections were stained
stimulus
is too
great, or
multiple(ROS)
stimuli act
simulgeneration of
reactive
oxygen
species
in various
levels are elevated in the Zuckerwith
Diabetic
Fattytrichrome.
(ZDF) rat
Gomoris
(eg, pressure overload plus diabetes),
tissues.40,41 taneously
heart, can initiate apoptosis and cardiac dysfunction.20,35 In
pathological accumulation of metabolites results in
Analysis
of
Myocardial
TAG
and
Ceramide
Levels.
The
quantitative
Comparedmetabolic
with fattymaladaptation.
acids, relatively little is known about
addition, fatty acids may affect cellular processes through
analysis of myocardial TAG species
(12) and
(13) by on cardiac gene expression.
the effects
of ceramide
glucose metabolism
reactive oxygen species.36
Fig. 1. The diabetic cardiac phenotype is influenced by the activity of PPAR!.
electrospray ionization mass spectrometry (ESIMS) has been
(a)that
PPAR
!-null mice
are resistant to development of diabetic ventricular
It
has
been
known
for
some
time
glucose
availability
described.
hypertrophy. (Left) Bars represent mean (" SEM) BV!BW ratios (n " 11) of
affects the expression of several specific
genes in the livGlucose-Regulated Gene Expression
PPAR!!/! and PPAR!$/$ mice 6 weeks after an injection of vehicle or STZ.
44 These genes include those encoding for pyruvate
As is true for fatty acids, glucose has
multiple
functions
in theNorthern
er.42
Northern
Blotting
Analyses.
blotting
analyses were per(Right) Bars represent mean cellular capacitance (n " 12) of isolated cardioformed
as use
described
by using kinase
radiolabeled
probes
for
myocytes
from PPAR
!!/! and
PPAR!$/$ mice 6 weeks after injection of vehicle
myocyte, extendingJanuary
far beyond
its
as an (14)
energy
! (ACC
!), fatty
acid
(PK), cDNA
acetyl-CoA
carboxylase
392cardiacCirculation
23,
2007
or STZ.
vs. vehicle-injected PPAR!!/! and all PPAR!$/$ mice. (b)
acyl-CoA
and human
glyceraldehyde-3*, P # 0.05
source. Once transported into the murine
cardiomyocyte
viaoxidase
specific(ACO)synthase
(FAS),
and Spot 14 (S14).
Through
investigations
Ventricular hypertrophy and dysfunction are exacerbated in diabetic MHCphosphate dehydrogenase.
63
regulatorySuch
transporters
transporters
[GLUTs]
1, 4,
concentrating
on the
responsive
eleproteins.
O-linked(glucose
glycosylation
of signaling
proteins
heart
also reverts
to aglucose/carbohydrate
fetal pattern
gene
expression.
PPARof
mice
(Lower
Left). Bars
represent mean (" SEM) BV!BW ratios (n " 7) of
and 8),atglucose
phosphorylated
by
hexokinase
to
ments
(GIRE/ChoRE)
in
the
promoter
regions
of
these
MHC-PPAR
and
NTG
littermate
occurs
serine becomes
and threonine
residues
otherwise
used
for
Therefore, oneGlutathione
or more common
signals must be present inmice after an injection of saline vehicle or STZ.
Analyses of H2O2 Levels and Reduced!Oxidized
(GSH)
(Lower
Right) Bars
represent
mean percent LV fractional shortening (n " 7 for
58 The
generate glucose
6-phosphate.
The
latter
has
multiple
potenvarious
glucose
regulated
genes,
a number
ofheart.
candidate
level
of
cytosolic
UDP-Nregulatory
phosphorylation.
the fetal,
hypertrophied,
and
unloaded
This
Ratios. Hydrogen peroxide levels
(15) diabetic,
and reduced
GSH
each group) as assessed by echocardiographic analysis 6 weeks after an
tial fates.
These include
through
glycolytic
pathway
transcription
factors
have
been
identified
that
are
believed
to
and
oxidized
GSH
(GSSG)
(16)
were
determined
as
acetyl
glucosamine,
the flux
principal
endthe
product
of the
hex- levels
common factor is most likely glucose.
The
evidence
as
injection
of vehicle
or STZ.is
*, P # 0.05 vs. vehicle-injected NTG mice. **, P # 0.05
described.
and full biosynthetic
oxidation via
the Krebs
cycle
(or substrate
conversion
to
be
involved
in
glucose
mediated
gene
expression.
Upstream
osamine
pathway
and
the
donor
used
vs.
NTG
mice
and
vehicle-injected
MHC-PPAR mice. (Upper) Representative
follows (Figure 2).
Figure
4. Maldistribution
of sympathetic
two-dimensional
guided
M-mode
images of the LV obtained from the
lactate),
storageglycosylation,
as glycogen, entry
pentose phosphate
stimulatory
factor
(USF),
stimulatory
protein
1
(Sp1),
and
for
protein
is into
ratethelimiting
for the
Glucose is the primary fuel used by the fetal heart. At birth,
Statistical Analysis.
Statistical
comparisons
were made
by using
parasternal view
at the mid-ventricular
of control and diabetic NTG and
innervation
in cardiac
autonomiclevel
neurop59 Levels
sterol
regulatory
element
binding
protein
1
(SREBP1)
have
pathway (PPP) with
concomitant
ribose
formation,
carbon
of
O-glycosylation
of proteins
(Figure
2, right).
increased
dietarysfatty
not
only
in increased
MHC-PPAR
mice.
unpaired t test or ANOVA coupled
to Scheffe
test acids
when result
athy
(MIBG).
MUGA
indicates multiple
UDP-N-acetyl glucosamine are appropriate.
in turn dependent
on are
thepresented as means " SEM, with a
All data
gated acquisition scan.
TABLE 1. Fatty
AcidInduced
Their
Role
Selection
Mitochondrial
uptake and metabolism
of glucose,
as wellGenes
assignificant
theand
activity
of in Fuel
statistically
difference
defined
a and
value
of P #Alterations
0.05.Metabolism
TABLE
2. as Transcriptional
During Pressure Overload
response independent of changes in BW, whole-cell membrane
glutamine:fructose
6-phosphate amidotransferase (GFAT),
and Diabetes
Gene Encoding for
Protein
Function
References(C ) was used as a measure of myocyte volume in
capacitance
Results
m
the rate limiting enzyme in hexosamine
biosynthesis.60,61 Sp1
cardiomyocytes
isolated from diabetic mice. Consistent with
Fatty acid translocase (FAT/CD36)
113, 114 Diabetes
Hypertrophy
The
Expression
of
the
Diabetic
Cardiomyopathic
Phenotype
Is
Influis regulated by both reversible phosphorylation and reversible
Fatty acid transport into the cell
RV ,,Aritmii
- b.endocrine"
martie
2016
the increased BV!BW
ratio in diabetic
PPAR!!/!
but not
in

MEDICAL SCIENCES

Echocardiographic Studies. Transthoracic M-mode and twodimensional

were
performed
consciousof alternative cellular compoof transport into the mitochondrion (eg, becauseechocardiography
of excessive
utilization
for theongeneration
mice by using an Acuson Sequoia 256 Echocardiography system
nents,
and entry
the hexosamine
biosynthetic pathway.
fatty acid availability and/or CPTI
inhibition
by malonyl(Acuson,
Mountain
View, CA), as
described
(11).into
Methods
for
Increased
through
thehave
latter pathway leads to increased
CoA), cytosolic LCFACoA levels
increase. The
latter
areand chamber
measurements
of LV
mass
sizeflux
using
M-mode
O-linked glycosylation of proteins, affecting various proutilized in the synthesis of both been
diacylglycerol
described (DAG)
(11). and

Finck BN et al. PNAS 2003

Young ME, McNulty P, Taegtmeyer H, Circulation 2002

Vinik AI, Ziegler D. Circulation 2007

enced by the Activity of PPAR!. To determine whether the

21

DM - arrhythmias
Arrhythmias
HRV
resting tachycardia
Orthostatic Tachycardia and Bradycardia
Syndromes
A.T. / A.FL / A.Fib (including fetuses and
neonates of diabetic mothers!)
Malignant ventricular arrhythmias

RV ,,Aritmii - b.endocrine" martie 2016

22

observed in this trial in patients with diabetes mellitus. Second,

patients with diabetes mellitus may be more immobile and

vention. The result

a secondary preven

Figure
cumu
patien

Ruwald MH et al,Downloaded
Circulationfrom
2013
http://circ.ahajournals.org/ by RADU VATASESCU
DM vs ICD in primary prophylaxy MADIT-RIT

RV ,,Aritmii - b.endocrine" martie 2016

23

Villous adenoma, Zollinger-Ellison syndrome

Hyperaldosteronism - arrhythmias

Mechanisms

Table 4. Electrophysiological effects of hypokalem

t has been suggested that extracellular K+ ions
are
Cardiology Journal 2011, Vol. 18, No. 3
equired to open the delayed rectifier channel [7].
Decrease
in conduction velocity
importantly,
Tissularhypokalemia alters the
conduction
disturbances
Most
conShortening of the effective refractory period
iguration of the
action potential (AP), with the du Fibrosis
Prolongation of the relative refractory period
ation of phase 2 first increasing and subsequently
Myocyte hypertrophy
Increased automaticity
decreasing, whereas the slope of phase 3 deceleEarly afterdepolarizations
Apoptosis
ates. The latter
effect leads to an AP with a long
Disarray
tail, resulting
in an increase in the relative refracory period (RRP) and a decrease in the difference
Extracellular
of the resting
membrane potential from the threshTable 5. ECG manifestations of hypokalemia.
+
old potential
during
the
terminal
phase
of
the
AP.
hypo-K
Thus, cardiac tissue demonstrates increased excitRepolarization changes
TDR
ability with associated ectopy for a considerable
Decreased
amplitude
and
broadening
Figure 1. Diagram of the ventricular
action potential
superimposed
on the
ECG at different extracellular potas
trations
(4.0,
3.0,
2.0
mEq/L).
The
numbers
on
the
left
designate
the
transmembrane
potential in millivolts. Fro

EAD
of
the
T
waves
portion of the AP. Conduction slows because depoProminent U waves
arization begins in incompletely repolarized fibers.
include:
QRS
duration depression
without
segment
Furthermore, hypokalemia prolongs the plateau
in increase inST
Hyperkalemia
a concomitant change in the QRS configuration; atriohe Purkinje fibers but shortens it in the ventricuand arrest;
U waves
fusion
(in severe
hypokalemia)
ventricular block (AV);Tcardiac
increase
in
Although less
common than hypok
P
wave
amplitude
and
duration;
and
slight
prolonperkalemia
may
affect
approximately 8
ar fibers [12]. The AP tail of the conducting sysConduction abnormalities
gation of the PR interval.
talized patients in the United States. Hy
em prolongs more than that of the ventricles, inIncrease in QRS duration
is seen mainly in the setting of compro
Arrhythmogenic potential and
function, particularly in association with
creasing the dispersion of repolarization. Hypokaleblock stration of a variety of nephrotoxic m
clinical implications Atrioventricular
of hypokalemia
Hypokalemia-induced
hyperexcitability
Hyperkalemia may result from either
mia increases diastolic depolarization in Purkinje
Cardiac
arrest is clinically manifested by an increase in supraventricular
excretion or a shift of potassium from w
ibers, thereby increasing automaticity.
Increase
in P wave
and ventricular ectopy.
In the Framingham
Off- amplitude
(Table 6). and duration
spring
Study,
potassium
and
magnesium
levels
In summary, the EP effects of hypokalemia
Slight prolongation of the P-R interval

effects of hyp
were inversely related to the occurrence of RV
com,,AritmiiElectrophysiological
- b.endocrine" martie 2016
24

Hyperaldosteronism - arrhythmias
Atrial arrhythmias
atrial fibrillation
atrial flutter (typical/atypical)
Focal atrial tachycardias (localized re-entry)

Ventricular arrhythmias
TdP
Monomorphic VT (rare, associated with LVH)
VF
RV ,,Aritmii - b.endocrine" martie 2016

25

The temperature was 36.6C, the blood pressure was 138/

78 mm Hg, the pulse rate was 101 beats/min, and the
respiratory rate was 25 breaths/min. Oxygen saturation was
100% while patient was receiving 100% oxygen through a
.revespcardiol.org, day 28/11/2013. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.
American
Journal of Emergency
Medicine
(2012) 30,to257.e5257.e7
mask attached to a bag-valve ventilation system. On physical
A 78-year-old
man was
admitted
the hospital
examination, the pupils were 3 mm in diameter, equal, round,
because of suddenly losing his consciousness. His family
and reactive to light. There was no sign of trauma to the head
had seen the patient slept 2 hours before and then saw him
mon presentation that has previously been described in
literature. We presented one case of torsades de pointes due
to primary hyperaldosteronism.

Scientific letters / Rev Esp Cardiol. 2012;65(5):479488

487

www.elsevier.com/locate/ajem

Case Report
Torsade de pointesa rare presentation of
primary hyperaldosteronism

suddenly stopped, unconscious, and cannot be awaken, with

rapid respirations.
He was brought to a local hospital immediately. On arrival
in the emergency department, the patient was unresponsive to
Abstract
verbal and physical stimulation. A patient was given a score
Document downloaded from http://http:://www.revespcardiol.org, day 28/11/2013. This copy is for personal use. Any transmission of this document by any media or format is str
of 3 on the Glasgow coma scale. An electrocardiogram
Primary aldosteronism was the most common form of
obtained 5 minutes after the patient's arrival showed torsade
endocrine hypertension resulting in hypertension, metabolic
de pointes (Fig. 1). Spontaneous recovery within few minutes
alkalosis, and hypokalemia. Ventricular arrhythmia in
Scientific letters / Rev Esp Cardiol. 2012;65(5):479488
was noted without any medications.
association with primary hyperaldosteronism is an uncomThe temperature was 36.6C, the blood pressure was 138/
mon presentation that has previously been described in
78 mm Hg, the pulse rate was 101 beats/min, and the
literature. We presented one case of torsades de pointes due
respiratory rate was 25 breaths/min. Oxygen saturation was
to primary hyperaldosteronism.
100% while patient was receiving 100% oxygen through a
mask attached to a bag-valve ventilation system. On physical
A 78-year-old man was admitted to the hospital
examination, the pupils were 3 mm in diameter, equal, round,
because of suddenly losing his consciousness. His family
and reactive to light. There was no sign of trauma to the head
had seen the patient slept 2 hours before and then saw him

Fig. 1

An electrocardiogram obtained 5 minutes after the patient's arrival showed torsade de pointes.

0735-6757/$ see front matter. Crown Copyright 2012 Published by Elsevier Inc. All rights reserved.

am showing an intense hypokalemia with prolonged QT interval. B, electrocardiogram after resolving hypokalemia with normal QT

e of a white 50-year-old man who was

cause he suffered a syncopal episode while
an accident. The only interesting aspect of
as that he was diagnosed with arterial
hs before. He started treatment with
sartan 160 mg and hydrochlorothiazide
te control. Since then he said that he
, had polyuria and polydipsia, without

A transthoracic echocardiogram was performed, which ruled

out structural heart disease. In view of an aetiological diagnosis,
the adrenal function was examined, which showed high plasma
aldosterone concentrations and absence of plasma renin activity. A
thoracoabdominal computerised tomography scan was also
performed showing a lobulated homogeneous tumour of
6.8 cmx6.2 cmx4 cm dependent on the left adrenal gland
(Fig. 2A) which did not affect other organs. Diagnosis was therefore

American Journal of Emergency Medicine (2012)

RV ,,Aritmii - b.endocrine" martie 2016

26

Nabil El-She
Adrenal insufficiency - arrhythmias

011, Vol. 18, No. 3

Table 8. ECG manifestations of hyperkalemia.

Mild hyperkalemia (K = 5.57.5 mEq)
Tall, peaked, narrow-based T waves
Fascicular blocks (LAFB, LPFB)
Moderate hyperkalemia (K = 7.510.0 mEq)

d ECG is from a 74 year-old patient with a history of pacemaker implantation for sick sinus
ented to the Emergency Room with complaints of weakness. He went into asystole shortly
sium serum level at the time of the cardiac arrest was 10 mEq/L.

First-degree atrioventricular block

Decreased P wave amplitude followed by
disappearance of the P waves and sinus arrest
ST segment depression

Severe hyperkalemia (K > 10.0 mEq)

Atypical bundle branch block (LBBB, RBBB), IVCD
Ventricular tachycardia, ventricular fibrillation,
idioventricular rhythm
LAFB left anterior fascicular block; LPFB left posterior fascicular
block; LBBB left bundle branch block; RBBB right bundle
branch block; IVCD intraventricular conduction delay

an atrial and ventricular action potential superimposed on the ECG for extracellular potassium
and 12.0 mEq/L. The numbers on the left designate the transmembrane potential in millivolts,
he bottom designate extra cellular potassium concentration [mEq/L]. From [14].

RV ,,Aritmii - b.endocrine" martie 2016

27

Cardiology Journal 2011, Vol. 18, No. 3

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

RV ,,Aritmii - b.endocrine" martie 2016

28

Pheochromocytoma
(usually) paroxysmal arrhythmias

Sinus tachycardia
Atrial tachycardia / atrial fibrilation
PSVT / atrial flutter (contributing)
PVCs
NSVT
VT/VF (rarely)

RV ,,Aritmii - b.endocrine" martie 2016

29

e436
Park et al

Circulation

March 13, 2012

Ventricular Tachycardia
e437
e436 in Pheochromocytoma
Circulation
March 13,
2012

Figure 2. A and B, Adrenal computed tomography scans show

a hypervascular mass with central necrotic change involving the
left adrenal gland (arrowhead) with lymph node metastasis in
the left para-aortic space (arrow). C and D, Computed tomography scans show multiple metastatic pulmonary nodules in both
lungs. E, The I-123 metaiodobenzylguanidine scan shows several areas of abnormal uptake in the left upper posterior abdomen (arrowhead) and in the right lung field (arrow). F, Another
region of focal uptake is visible between the previous lung
lesions on the follow-up scan.

Figu
Figu
rapid
rapid
tach
tach
bloc
Fig
bloc
B,
N
rap
B,tac
N
tach
tach
was
blo
was
less
B,
less
cope
tac
cope
was
wa
was
nalec
les
nale
defib
cop
defib
cess
wa
cess
appr
nal
appr
defib
defi
defib
ces
app
defi

Figure 2. A and B, Adrenal computed tomography scans show

a hypervascular mass with central necrotic change involving the
left adrenal gland (arrowhead) with lymph node metastasis in
the left para-aortic space (arrow). C and D, Computed tomography scans show multiple metastatic pulmonary nodules in both
lungs. E, The I-123 metaiodobenzylguanidine scan shows several areas of abnormal uptake in the left upper posterior abdomen (arrowhead) and in the right lung field (arrow). F, Another
region of focal uptake is visible between the previous lung
lesions on the follow-up scan.

Figure 3. Changes in the levels of urinary catecholamine and its

metabolites. Before the adrenalectomy, urinary concentrations
of normetanephrine (!2000 !g/24 h; reference range, 82500
!g), vanillymandelic acid (VMA; 25.9 mg/24 h; reference range,
"9 mg), and norepinephrine (!2000 !g/24 h; reference range,
15 80 !g) were significantly elevated. They began to decrease
after removal of the mass and returned to within the normal

RV ,,Aritmii - b.endocrine" martie 2016

30

- IGT
- DM
Endothelial dysfunction
Acromegalic cardiomyopathy
- Left ventricular or biventricular hypertroph
- Diastolic dysfunction
- Heart failure (end-stage)
Valvular heart disease:
- Mitral and/or aortic annulus brosis/bros
- Leaet brosis/brosclerosis
- Leaet thickening
- Calcications
- Mitral and/or aortic regurgitation
- Aortic ectasia
Arrhythmias:
- Ventricular ectopic beats
- Paroxysmal atrial brillation
- Paroxysmal supraventricular tachycardia
- Sick sinus syndrome
- Ventricular tachycardia
- Bundle branch blocks
- Late potentials

Acromegaly - arrhythmias
Mechanisms
Hypervolemia
metabolism
biV hypertrophy

Diastolic disfx
Valve disease
LVD (late) and CHF

DM

Arrythmias
Sinus tachycardia
Similar to other HCM
(assoc. with exercise)

RV ,,Aritmii - b.endocrine" martie 2016

31

low-up.
ventricular
hypertrophy,
the possible presence inferior axis)
dle branch
block
morphology,
of areas of fibrosis in the myocardium may
responsible for the slowdown and
(Figure have
1A).beenTranssphenoidal
surgical resecnon-homogeneity in the propagation of action
(2, 3) that induced
the ventricular
tion of apotentials
pituitary
adenoma
had been perarrhythmias in our patient. The presence of a
DISCUSSION
formed five
Serum levels of
cochlearyears
implant previously.
contraindicated magnetic
resonance imaging, which might have demonCardiovascular disease is an important
growth hormone
(GH)
and
insulin-like growth
strated the existence
of areas
of fibrosis.
In conclusion, careful evaluation of cardiac
factor-1 function,
(IGF-1)
were
0.3
and 138 ng/ml complication of acromegaly, accounting for
morphology,
and activity
at diagnosis
and during follow-up appears to be essential
in the management of patients with
acromegaly. Malignant ventricular tachyarrhythmias may account for some cases of
recurrent syncope and sudden cardiac death
in acromegalic patients, even in those with an
Figure 3. Detail of the patients hands
apparently normal heart.
Figure 2. Typical features of acromegaly in the patient

d by structural abnormalities including

rstitial fibrosis with extracellular deposiof collagen and myofibrillar derangement,
as of monocyte necrosis and lymphocyte
ltration. The development of ventricular
unction and progression to cardiac failure
y be related to increased myocyte apoptosis.
Normalizing GH and IGF-1 levels can slow
even halt the progression of cardiovascudisease, reducing both cardiovascular mor-

e 3. Detail of the patients hands

225

Address for reprints:

Dr. Miguel A. Arias

Unidad de Arritmias y Electrofisiologa Cardiaca
Hospital Virgen de la Salud, Planta Semistano
Avda. Barber 30, 45004 Toledo, Spain
Phone: +34637463857 Fax: +34925265492
E-mail: maapalomares@secardiologia.es

Rev Port Cardiol 2011

Figure 1. Twelve-lead electrocardiogram showing 225clinical ventricular tachycardia

RV ,,Aritmii - b.endocrine" martie 2016

32

Hyperparathyroidism - arrhythmias
APD QTc
VPBs
VF (severe & acute)

ST elevations
Ca2+ depositions:
AVB
BBB

RV ,,Aritmii - b.endocrine" martie 2016

33

Hypoparathyroidism - arrhythmias
APD
QTc
Low amplitude / flat / inverted T wave

TdP

RV ,,Aritmii - b.endocrine" martie 2016

34

 What we seek we shall find; what

we flee from flees from us.
Ralph Waldo Emerson (American Poet, Lecturer and
Essayist, 1803-1882)
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35