Aritmiile cardiace

în bolile endocrine

Dr. Radu Vătăşescu

Laboratorul de Pacing şi Electrofiziologie Clinică
Clinica de Cardiologie
Spitalul Clinic de Urgenţă Bucureşti
 Aritmii çè boli endocrine
Substrat indus Agravate/demascate=
substrat pre-existent

•  Fibroza •  pe cord N
•  HV •  pe cord patologic
•  Cicatrice
–  IM
–  miocardite
•  Anomalii ionice

RV ,,Aritmii - b.endocrine" martie 2016 2

 Tiroida si sistemul cardio-vascular
•  disf(x) tiroidiene çè morbi-mortalitate c-v
Gencer et al Thyroid Dysfunction and Heart Failure 1

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, 1.27–2.72) 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
TABLE 1. CHANGES IN CARDIOVASCULAR FUNCTION d
ASSOCIATED WITH THYROID DISEASE.*
a
VALUES VALUES t
NORMAL IN HYPER- IN HYPO-
MEASURE RANGE THYROIDISM THYROIDISM
t
c
Systemic vascular resistance 1500–1700 700–1200 2100–2700
(dyn·sec·cm¡5)
t
Heart rate (beats/min) 72–84 88–130 60–80 h
Ejection fraction (%) 50–60 >60 «60 n
Cardiac output (liters/min) 4.0–6.0 >7.0 <4.5 t
Isovolumic relaxation time (msec) 60–80 25–40 >80 s
Blood volume (% of normal value) 100 105.5 84.5 i
Klein I, Ojamaa J. NEJM 2001 u
*The values for patients with hyperthyroidism and those with hypothy-
roidism are taken from Klein and Levey,6 Graettinger et al.,7 Mintz et al.,8 p
RV ,,Aritmii - b.endocrine" martie 2016 4
 Efecte h-d

Klein I, Danzi S. Circulation 2007 RV ,,Aritmii - b.endocrine" martie 2016 5

 TREs as homodimers or, more commonly, as heterodimers

Mecanisme i-celulare
Myopathy 359.9
with 1 of 3 isoforms of retinoid X receptor (RXR!, RXR", or
ICD-9 indicates International Classification of Diseases, Ninth Edition.
RXR#).16 While bound to T3, TRs induce transcription, and in

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 mecha-
RV ,,Aritmii - b.endocrine"
nisms involve T3 binding to TRs, which regulate transcription of specific cardiac genes. Nongenomic mechanisms include direct modu-martie 2016 6
Table 2. Effect of Thyroid Hormone on Cardiac Gene con
Expression hem
Positively Regulated Negatively Regulated
Eff
"-Myosin heavy chain !-Myosin heavy chain
He
Sarcoplasmic reticulum Ca2!-ATPase Phospholamban Thy
Na!/K!-ATPase Adenylyl cyclase catalytic subunits latu
!1-Adrenergic receptor Thyroid hormone receptor "1 left
Atrial natriuretic hormone Na!/Ca2! exchanger Thy
Voltage-gated potassium channels arte
(Kv1.5, Kv4.2, Kv4.3) arte
the
Non-genomic (direct) T3-mediated effects (heart and VMC):
sod
the -ion
absence of (sodium,
channels T3 theypotassium,
repress transcription.
and calcium)
17 Negatively
wh
regulated cardiac genes such as !-myosin heavy chain and
-actin polymerization com
-adenine nucleotide
phospholamban translocator
are induced in 1the
(mitochondrial
absence of membrane)
T3 and re- In h
pressed in the presence of T3 (Table 2).18 –20 out
Thyroid hormone effects on the cardiac myocyte are
Klein I, Danzi S. Circulation 2007 hyp
intimately associated with cardiac function via regulation of opp
RV ,,Aritmii - b.endocrine" martie 2016 7
 Aritmii atrialeçè Hypertiroidism
Induse Agravate/demascate=
substrat pre-existent

•  tahicardia sinusală* •  macro-reintrări

•  ESA –  TRNAV (,,intranodală)
–  TRAV (cale accesorie)
•  TA nesustinută si polimorfă –  Flutter A tipic
•  fibrilația atrială$ –  Flutter A pericicatr.
•  focale (tahicardii atriale)
* în lipsa altor cauze de TS
-anemie
–  automatism aN
-ICC –  micro-reintrari
-TEP –  activitate declansată
-sevraj, etc

$apariția sau agravarea poate fi primul semn la

varstnici; la tineri aparitia de novo ≈niciodată fără
alte semne de hipertiroidism

RV ,,Aritmii - b.endocrine" martie 2016 8

 afterdepolarization (DAD) in a pulmonary vein beating cardiomyoc

Aritmogeneza in hipertiroidism
(n # 34) During electrical stimuli of 0.1 Hz, there were two DAD after comp
Atrial (n # 16) 64 ! 1 98 ! 4 120 ! 15 240 ! 14 repolarization. Arrows indicate the occurrence of DAD.
Table 1. The AP Parameters
Values are means in! SE.the Hyperthyroid
*p " 0.05;
from control cells by Tukey test.
†p " 0.005; ‡p " 0.001and Control
significantly different
AP occurred after complete repolarization, which was co
PV Cardiomyocytes or APAtrial Myocytes
# action potential; APA # amplitude of AP; APD and APD # action
potential duration at 50% and 90% repolarization, respectively; MDP # maximal
50 sistent with DAD.
90

diastolic potential; PV # pulmonary vein. PV cardiomyocytes without spontaneous activities.

JACC Vol. 39, No. 2, 2002
Figure 2. Effects of thyroid hormone on the occurrence of delayed MDP APA APD50January 16, 2002:366–72
APD90 the example shown in Figure 3, the AP duration Thyroid (APD
Hormo
afterdepolarization (DAD) in a pulmonary vein beating cardiomyocyte.
During electrical stimuli of 0.1 Hz, there were two DAD after complete spontaneous (!mV) (mV)
activities, and 34 cells (ms)
did not have (ms)
spontane- and APD 90 ) of the hyperthyroid PV cardiomyocytes w
repolarization. Arrows indicate the occurrence of DAD. ous activities. The electrical capacitance was similar between shorter than that of control PV cardiomyocytes (Table 1).
AP occurred after complete Hyperthyroid was con- the hyperthyroid and control PV beating cardiomyocytes
repolarization, whichcardiomyocytes
the atrial cells, there was shorter AP duration (APD50)
sistent with DAD. (168 ! 28 pF vs. 143 ! 24 pF), nonbeating cardiomyocytes hyperthyroid cardiomyocytes than there was in cont
PV beating cells (n # 26) 55 ! 1 93
PV cardiomyocytes without spontaneous activities. As (136 ! 16 pF vs. 125 ! 8 pF) and atrial cells (155 ! 24 pF
! 2 155 ! 12‡ 278 ! 10‡ cardiomyocytes.
the example shown in Figure PV Nonbeating
3, the cells50 vs. 149 !62
AP duration (APD 28 ! pF).2 JACC94 !No.22, 2002118 ! 20† 286 ! 21‡ During electrical stimulation, Chen
Vol. 39, nine
et al.(45%)
369 of the
and APD90) of the hyperthyroid PV cardiomyocytes were PV cardiomyocytesJanuary
(n # 20) with
JACC 16, spontaneous
Vol. 39,2002:366–72
No. 2, 2002 activities. The hy- hyperthyroid non-beating
Thyroid Hormone PV
on PV cardiomyocytes
Cardiomyocytes
Chen et al. 369have DA
shorter than that of control PV cardiomyocytes (Table 1). In perthyroid PV beating January 16, 2002:366–72
cardiomyocytes had a faster beating which was Thyroid
higher Hormone
than the on PV Cardiomyocytes
incidence of DAD in control P
the atrial cells, there was shorterAtrial AP (n # 14)
duration (APD50) in rate than 62 ! 2 96 ! 1 52
the control PV beating cardiomyocytes (1.82 !! 14* 176 ! 18
hyperthyroid cardiomyocytes than there was in control
cardiomyocytes.
Control cardiomyocytes 0.13 Hz vs. 1.03 ! 0.15 Hz, p " 0.005). The AP duration
During electrical stimulation, PV beating
nine (45%) cells
of the(n 20
# 36)(APD50, APD 57 !90)1of the 92 hyperthyroid
! 3 220 ! PV16 beating383 cardio-
! 28
hyperthyroid non-beating PV cardiomyocytes have DAD, myocytes was shorter than that of control PV beating Figure 2. Effects of thyroid hormo
PV Nonbeating cells
which was higher than the incidence of DAD in control PV cardiomyocytes.
63 ! 1 92 ! 2 231 ! 18 374 ! 22 afterdepolarization (DAD) in a pulm
(n # 34) During electrical stimulation or in spontaneously beating During electrical stimuli of 0.1 Hz, th
Chen et al. myocytes, 64 12 ! (46%) of the JACC Vol. 39,
26 hyperthyroid PVNo. 2, 2002
beating
Atrial
Thyroid Hormone on PV Cardiomyocytes (n # 16) 1 98 ! 4 120 ! 15
January 240 ! 14 repolarization. Arrows indicate the oc
cardiomyocytes had EAD, and 24 (92%) of 16,
the2002:366–72
hyperthy-
Values are means ! SE. *proid PV beating
" 0.05; †p " cardiomyocytes
0.005; ‡p " 0.001 had delayed afterdepolar-
significantly different
1. The AP Parameters in the Hyperthyroid and Control
ardiomyocytes or Atrial Myocytes from control cells by Tukey test. ization (DAD). In contrast, none of the 36 control PV AP occurred after complete rep
beating cardiomyocytes had EAD (p " 0.0001 vs. hyper-
MDP APA
AP #APD action potential;
APD90
APA # amplitude of AP; APD50 and APD90 # action
thyroid cells), and only two (6%) of the cells had DAD (p " sistent with DAD.
potential duration at 50% and 90% repolarization, respectively; MDP # maximal
50
(!mV) (mV) (ms) (ms)
hyroid cardiomyocytes
diastolic potential; PV # pulmonary
0.0001 vs. hyperthyroid cells). Figure 1 shows an example of
the hyperthyroid vein. PV beating cardiomyocytes with the oc- PV cardiomyocytes without
ting cells (n # 26)
nbeating cells
55 ! 1 93 ! 2 155 ! 12‡ 278 ! 10‡
62 ! 2 94 ! 2 118 ! 20† 286 ! 21‡
currence of EAD during spontaneous beating. Figure 2 the example shown in Figure
shows the other example of the hyperthyroid PV cardiomy-
20)
n # 14)
spontaneous activities, and 34 cells did not have spontane-
62 ! 2 96 ! 1 52 ! 14* 176 ! 18 ocytes with DAD. During electrical stimuli, the triggered
and APD ) of the hyperthyro
90
l cardiomyocytes ous activities. The electrical capacitance was similar between shorter than that of control PV
ting cells (n # 36) 57 ! 1 92 ! 3 220 ! 16 383 ! 28
nbeating cells 63 ! 1 the92 ! 2 hyperthyroid
231 ! 18 374 ! 22
Figure 2. Effects of thyroid hormone on the occurrence of delayed
and control(DAD)
afterdepolarization PVin a beating
pulmonary vein cardiomyocytes
beating cardiomyocyte. the atrial cells, there was shor
Figure 4. Membrane currents of a hyperthyroid (A) and a control (B) pulmonary vein (PV) cardiomyocyte. The ionic currents were elicited on
34) During electrical stimuli of 0.1 Hz, there were two DAD after complete
n # 16) 64 ! 1 (168
98 ! 4 120 !!28 15 pF 240 ! vs.
14 143 ! 24Arrows
repolarization. pF),indicatenonbeating
the occurrence of cardiomyocytes hyperthyroid cardiomyocytes
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
DAD.
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

ntrol cells by Tukey test. (136 ! 16 pF vs. 125

re means ! SE. *p " 0.05; †p " 0.005; ‡p " 0.001 significantly different
! 8 pF)
AP occurred after and
complete atrial cells (155 ! con-24 pF has thecardiomyocytes.
currents (Ik) were indicated by circles and triangles, respectively.
repolarization, which was
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).
potential; PV # pulmonary vein.
vs. 149 ! 28 pF). PV cardiomyocytesbeating
duration at 50% and 90% repolarization, respectively;
50
MDP #
90
maximal
without
0.005).
The incidence
spontaneous
cardiomyocytes
The incidence
of EAD
(one
of EAD
in
non-beating cardiomyocytes (one in 34 cells, 3%, hyperthyroid
in 20inactivities.
cells, 5%) was As
hyperthyroid
PV non-
p !
similar
PV non- to
progressively
steps.
During
has the propertiesin amplitude
The depolarizing
progressively in amplitude
electrical
with increasing
of rapid activation
stepswith
also increasing
induced a slowly
stimulatio
kineticsdepolarization
and increased
activat-
depolarization
PV cardiomyocytes with spontaneous the example shown that
beating
in
cells,
that in
Figure
0%).
control
3, activities.
in cardiomyocytes
control PV non-beating
In atrial
PV
the
cells,
(one
AP
non-beating
in 20
duration
the incidence of The
cardiomyocytes
cells, 5%)
(APDwas
DAD (one
cardiomyocytes
50hy-
(0 in 34
similar
(0 in 14
to
34
ing
steps.
the hyperthyroid
non-inactivating
The depolarizing
ing characteristics
non-inactivating
steady
steps
of steady
state
delayedstate
also
non-beating
outward
induced
rectifier
current
outward
outward
a slowly
current
similar to
activat-
current.
similarThe
to
PV
aneous activities, and 34 cells did not have spontane- and APD90) of thecells, hyperthyroid PV cardiomyocytes were
tivities. The electrical capacitance perthyroidwas similar PV between beating
shorter cardiomyocytes
Figure 1.than that
Effects of of control
7%) or
0%).
incidence
cells, 7%)
thyroid
In EAD
PV
of
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Figure 3. Effects of thyroid hormone
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than
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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
2-Hz pacing train. Table 1
Biochemical Characteristics of the Patients longation of
y flow cytometry. Puri- potential dur
Atrial Normal Sinus
(1:200) with isotonic Fibrillation Rhythm after a 20-be
4% bovine serum albu- (n ! 17) (n ! 21) p Value 250, 500, 1,0
incubated with Chinese Age (yrs) 60.9 $ 12.7 45.7 $ 13.1 0.001* presence of I
ngth human thyrotropin Male (%) 47.1 42.9 1.00 for each paus
Antihuman IgG (H!L) Hypertension (%) 70.6 61.9 0.73
prolonged pa
Diabetes mellitus (%) 35.3 23.8 0.49
cyanate (BD Bioscience action potent
Coronary artery disease (%) 17.6 9.5 0.64
was the secondary anti- depolarizatio
Heart failure (%) 52.9 23.8 0.09
y was measured by flow local autonom
Ejection fraction (%) 51.6 $ 16.1 52.4 $ 16.2 0.88
en). A human monoclo- Left atrium (mm) 42.3 $ 7.8 38.3 $ 7.6 0.15
79% of the p
R that stimulates cyclic E (m/s) 0.83 $ 0.25 0.98 $ 0.37 0.17 IgG, respecti
1312 Stavrakis et al. JACC Vol. 54, No. 14, 2009
-TSHR cells confirmed DT (ms) Antibodies in Graves’ AF 245.2 $ 72.2 242.4 $ 77.9 0.90 of the stimu
Antiautonomic Receptor September 29, 2009:1309–16
E/E= 5.9 $ 2.5 6.6 $ 2.5 0.50 significantly
HR cells were maintained Serum thyrotropin (mU/l) 0.075 $ 0.12 0.071 $ 0.18 0.94 the left (EV5
longation of the terminal action potential duration (action
d with 10% fetal bovine Serum free thyroxine (ng/dl) 2.35 $ 1.3 3.08 $ 2.3
potential duration 0.22
at 90% of repolarization) was enhanced IgG, respect
ia), 100 U/ml penicillin, after a 20-beat pacing afterdepolariz
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
gen, Grand Island, New ratio between the early diastolic velocity of mitral inflow (E) and250,
that of500, 1,000,(E=).2,000, and 4,000 ms, respectively,
mitral annulus stimulation–i
in the
detached by phosphate- presence of IgG compared with control subjects (p !(32 lol 0.01nmol
thylenediaminetetraacetic sinus rhythm (60.9 $ 12.7 years vs. 45.7 for$ each13.1 pause
years, duration).
p % With rapid pacing followed ening, byand
a lo
etic acid. Counted (1 " 0.001). Otherwise, no difference was noted prolongedfor the pause, prolongation of the terminal phase
percent- gered firing w
of the
0 !l of diluted (1:200) age of male sex, presence of hypertension, diabetes mellitus, action potential clearly assumes the form of an early after-
Determinan
depolarization (Figs. 2B and 2C). Triggered firing for 14 withvaria
ocking at room tempera- coronary artery disease, and congestive heart failure between
local autonomic nerve stimulation was observed inAA 50%!1AR and an
e collected by centrifuga- the 2 groups. Echocardiographic indexes, including left ven-
79% of the pulmonary sleeve preparations before creased and afterAA!
d using pre- and post- tricular ejection fraction, left atrial diameter, early diastolic
IgG, respectively (p " NS). The IgG decreased the voltage
velocity of mitral inflow (E), decelerationof time effects (perce
ction in mean fluorescent theofstimulus
mitral Etrain flow needed to induce triggered firing,
nt adsorption. All exper- velocity (DT), and the ratio between the early diastolic velocity
significantly moving the stimulus voltage-response curve to related to the
and post-adsorbed serum of mitral inflow and that of mitralStavrakis Functional
annulus the Effects
(E/E=)
left didofal.
(EV IgG
not"Jdiffer
70 2 V vs. 96 # 2 V after and thebefore
copresenc
Figure 1 From Patients S,With et 50 Am # Coll
Graves’ Disease and Cardiol 2009
by enzyme-linked immu- significantly between the 2 groups.Control SerumIgG, respectively,
thyrotropin p !
and free 0.001) (Figs. 2D and 2E). independent
Early
Subjects on Purkinje Fiber Contractility
RV ,,Aritmii
afterdepolarization formation and local autonomic - b.endocrine" martie interval
2016nerve[CI]11
Aritmii ventriculareçè Hipertiroidism
Induse Agravate/demascate=
substrat pre-existent

•  NICIUNA! •  pe cord N
–  ESV/TV de tract de ejecție
–  +/-TV idiopatica VS
(fasciculara)
•  pe cord patologic
–  CAVD
–  CMH
–  post-IM

RV ,,Aritmii - b.endocrine" martie 2016 12

 Hipertiroidism

ICC HTP
•  secundară tachyCMP •  usoară (PAPs 30-50 mm Hg)
•  răspuns spectaculos la bB •  de debit
•  revers-remodelare
spectaculoasă

RV ,,Aritmii - b.endocrine" martie 2016 13

Klein and Danzi Hipotiroidism
Thyroid Disease and the Heart 1731

en Table 4. Cardiovascular Risks Associated With

s, Hypothyroidism
t- Impaired cardiac contractility and diastolic function
be
Increased systemic vascular resistance
ed
Decreased endothelial-derived relaxation factor
ed
to Increased serum cholesterol
Increased C-reactive protein
Increased homocysteine

p-
hypertension (diastolic), narrowed pulse pressure, cold intol-
st Klein I, Danzi S. Circulation 2007
erance, and fatigue.10,28 Overt hypothyroidism affects "3%
nd RV ,,Aritmii - b.endocrine" martie 2016 14
 Aritmii - hipotiroidism

Atriale Ventriculare
•  bradicardie sinusală •  LQT
•  ESV
•  TdP (exceptional)

RV ,,Aritmii - b.endocrine" martie 2016 15

 Interactiuni c-v -- tiroida
1732 Circulation October 9, 2007

1.0
EF > 20 % & total T3 > 1.2 nmol/L

P=0.002
.9
EF 20 % & total T3 > 1.2 nmol/L

P<0.0001
Survival

.8

P=0.02
EF > 20 % & total T3 1.2 nmol/L

.7

EF 20 % & total T3 1.2 nmol/L

.6
.

.5

.4
0 6 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 cardio-
vascular 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, levels.107–109 The decrease in serum T3 is proportional to the
rather than worsen, with treatment. 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 unde- and TSH levels, and the syndrome
RV ,,Aritmiiresults from impaired
- b.endocrine" hepatic
martie 2016 16
 Analogi ai h.tir.
Eprotirome Treatment of Hypercholesterolemia

Placebo Eprotirome, 25 µg Eprotirome, 50 µg Eprotirome, 100 µg

 
 +  * **+


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0 4 8 12 16 0 4 8 12 16
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Landeson
Figure 1. Effects PW,
of Eprotirome et al.Levels
on Serum N Engl J Med
of Cholesterol, 2010 and Triglycerides.
Lipoproteins,
AUTHOR: Ladenson RETAKE: 1st
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 é fact. coagulare é  metabolism vit K
é  metabolism ACO
084 Stuijver et al. Hyperthyroidism and coagulation •  >> pt acenocumarol
•  << pt warfarina

StuiverDJF
Figure 4: Haemostatic parameters for all medium-/high-quality et al. intervention
observational Thrombosis andprothrombin
studies. F1+2, Haemostasis 2012
fragment 1+2; pFN, plas-
ma fibronectin; cFN, cellulair fibronectin; VWF, von Willebrand factor; Ag, antigen; C, activity; PAP plasmin-antiplasmin complexes;
RV ,,Aritmii t-PA, tissue
- b.endocrine" type-plas-
martie 2016 18
 implantation. with more severe disease were treated with prednisone.

Amiodarona - tiroida
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
•  discrete aN ale testelor tiroidiene
Discussion
Considering the increased event rate, early thyroidectomy
may be worthwhile in selected cases because definite cure of
The present analysis confirms that medical therapy for AIT AIT can be achieved rapidly and long-term amiodaronetance of reduced left ventricular fun
•  hipotiroidismul ≠ indicație de oprire a AA
is challenging. It may take several months before euthyroid- therapy can be continued safely. Surgery is an optionpresence of left ventricular dysf
Duration
and in Patients
of Follow-Up
Stratified
and According
Incidence to of Left
the Primary
Ventricular Composite
FunctionEnd at Point
the Timein Allof Patients
AIT Diagnosis independent predictor of the pr
•  hipertiroidismul (I sau II) indicație de oprire a AA
Table 5
Duration of Follow-Up and Incidence of the Primary Composite End Point in All Patients
and in Patients Stratified According to Left Ventricular Function at the Time of AIT Diagnosis
multivariate analysis. This may be
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
Duration of follow-up (months) 50 (17–78) 50 (19–78) 44 (16–78) 0.54*
after AIT patients may remain
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)
2354 Conen et al. JACC Vol. 49, No. 24, 2007be considered as a therapeutic op
Ventricular fibrillation/tachycardia 10 (12) 2 (4) 8 (31)
Amiodarone-Induced Thyrotoxicosis
Implantation of defibrillator device 7 (8) 1 (2) 6 (23)
June 19, 2007:2350–5 analyses suggest that amiodarone
Pacemaker implantation 7 (8) 4 (7) 3 (12)
during and after AIT (16,17). H
Hospitalization for treatment complication 3 (4) tance of reduced
3 (5) left ventricular function
0 (15). However, 0.53‡ trolled data about continued amiod
the
presence of left ventricular dysfunction failed to be an with AIT are needed.
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.
independent predictor of the primary end point in the Clinical implications. In patien
multivariate analysis. This may be related to reduced statis- event rate suggests the need for clo
tical power because of the low number of patients in the therapy should be carefully selecte
Downloaded From: http://content.onlinejacc.org/ on 06/10/2013
group with reduced left ventricular function. Alternatively, thyroid ultrasound and Doppler
after AIT patients may remain at high long-term risk, ment of radioiodine uptake (19),
reducing the influence of left ventricular function on out- such as interleukin-6 (20) may be
come. This especially may be true when amiodarone as the AIT patients who may benefit f
most effective antiarrhythmic drug must be discontinued Early favorable response to a sho
permanently. might be another criterion for fin
Therefore, with regard to the high incidence of benefit from continuation of stero
arrhythmia-related events during long-term follow-up, con- tion of euthyroidism. Patients with
tinuation of amiodarone despite the occurrence of AIT may response to medical therapy a
be considered as a therapeutic option. Some uncontrolled thyroidectomy.
analyses suggest that amiodarone may be continued safely Because the findings from th
during and after AIT (16,17). However, prospective con- patients with AIT are at risk for co
trolled data about continued amiodarone therapy in patients period of time, prolonged follow-
with AIT are needed. tion of thyroid function should b
Conen D, et al, J Am Coll Cardiol
Figure Clinical
1 implications.
Event-Free Survival In patients with AIT, 2008 ticular,
the
RV ,,Aritmii - b.endocrine"
high clinicians should look for o
recurrence,martie 2016common19co
the most
 DM - arrhythmias
•  advGEPs, oxidative stress, polyol
–  ASC
–  Accelerated apoptosis, fibrosis, connexin 43 malfunction
–  é ventricular stiffness è éfilling pressure
•  GPZ deposition
•  LVH (PPAR-α mediated)
–  O-linked glycation of Ca2+/calmodulin-dependent PK II è
sarcolemal release è éCa2+ i-cel (Erickson JR et al, Nature 2013)
•  éfilling pressure
•  delayed afterdepolarizations
–  Cardiac neuropathy:
•  é sympathetic/parasimpathetic & maldistribution
•  Silent ischemia
•  é 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
depicted of side of the figure. Activation of
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
tyrosine control
kinases (RTK), and integrins in response
chow. to multiple stimuli result in the activation of numer-
ous signaling cascades, such as those employing
calcium
Isolation of Cardiac Myocytes and Electrophysiologic (Ca2!Adult
Studies. ), protein kinase C (PKC) isoforms,
cardiac ventricular myocytes were isolated,calcineurin, Ca2!/calmodulin kinase (CaMK),
and whole-cell
voltage-clamp recordings were obtained by using mitogen-activated
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
1864 Circulation AprilText, which is published as supporting information
16, 2002 on the generate
metabolism PNAS essential components
web site, www.pnas.org. involved in this adaptation (right).

Echocardiographic Studies. Transthoracic M-mode and two-

of transport into the mitochondrion (eg, becauseechocardiography
dimensional of excessive were performed
utilization for theongeneration
consciousof alternative cellular compo-
mice by using an Acuson Sequoia 256 Echocardiography system
fatty acid availability and/or CPTI inhibition
(Acuson, by malonyl-
Mountain View, CA), asnents, and entry
described (11).into the hexosamine
Methods for biosynthetic pathway.
CoA), cytosolic LCFACoA levels increase. The
measurements latter
of LV Increased
areand chamber
mass sizeflux through
using M-mode thehave
latter pathway leads to increased
utilized in the synthesis of both been described (DAG)
diacylglycerol (11). and O-linked glycosylation of proteins, affecting various pro-
ceramide. DAG is an allosteric activator of several PKC cesses such Figureas transcription,
3. Metabolic translation,
adaptationand and protein stabili-
maladaptation
isoforms. Increased DAG levels Histologic and PKC Analyses.
activity are After ob- harvest, a mid-ventricular
ty.37–39 of the heart.slice
As exemplified of stimuli
inVarious
Figure can result
2, glucose is morein rapid
than just

MEDICAL SCIENCES
served in myocytes isolated from myocardium
diabetic was snap-frozen
animals. 19,33 in an
a cryomold
energy source for sectioning
alterations
for thein fatty oracid
heart. and glucose
Failure metabolites
to adequately control
preserved in buffered formalin. To detect neutral within lipid, frozen
the cardiomyocyte. These metabolites then
Chronically activated PKC has been suggested to play a role intracellular
sections were stained with oil red O and counterstained glucose levels
act as essentialwith (glucotoxicity) has
signaling molecules for the adap- also been
in the development of insulin resistance. 34 Ceramide, whose implicated in
hematoxylin. To detect signs of fibrosis, sections were stained the
tation development
process. of
However, insulin
if the resistance
intensity and
of thein the
levels are elevated in the Zuckerwith Gomori’s
Diabetic Fattytrichrome.
(ZDF) rat generation of stimulus is too
reactive great, or
oxygen multiple(ROS)
species stimuli act simul-
in various
heart, can initiate apoptosis and cardiac dysfunction.20,35 In tissues.40,41 taneously (eg, pressure overload plus diabetes),
pathological accumulation of metabolites results in
Analysis of Myocardial
addition, fatty acids may affect cellular processes through TAG and Ceramide Levels.
Comparedmetabolic The quantitative
with fattymaladaptation.
acids, relatively little is known about
analysis of myocardial TAG species (12) and
the effects of ceramide (13) by on cardiac gene expression.
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
described. It has been known for some time Finck BN et al. PNAS 2003
(a)that
PPAR !-null mice
glucose are resistant to development of diabetic ventricular
availability
hypertrophy. (Left) Bars represent mean (" SEM) BV!BW ratios (n " 11) of
Glucose-Regulated Gene Expression affects the expression of several specific genes in the liv-
PPAR!!/! and PPAR!$/$ mice 6 weeks after an injection of vehicle or STZ.
As is true for fatty acids, glucose has multiple
Northern functions
Blotting in theNorthern
Analyses. blotting
er.42– analyses were per-
44 These genes include those encoding for pyruvate
(Right) Bars represent mean cellular capacitance (n " 12) of isolated cardio-
myocyte, extendingJanuary
392cardiacCirculation formed
far beyond 23,
its 2007
as use
described
as an (14)
energy by using kinase
radiolabeled
(PK), cDNA probes
acetyl-CoA for
carboxylase ! (ACC
myocytes !), fatty
from PPAR acid
!!/! and PPAR!$/$ mice 6 weeks after injection of vehicle
source. Once transported into the murine acyl-CoA viaoxidase
specific(ACO)synthase
and human glyceraldehyde-3- or STZ. *, P # 0.05 vs. vehicle-injected PPAR!!/! and all PPAR!$/$ mice. (b)
Young ME, McNulty P, Taegtmeyer H, Circulation 2002
regulatorySuch
proteins. transporters
O-linked(glucose
cardiomyocyte
phosphate dehydrogenase.
transporters
glycosylation [GLUTs]
of signaling 1, 4,
proteins concentrating
heart
(FAS),
also reverts
and Spot 14 (S14).
on theto aglucose/carbohydrate
fetal pattern PPARof
Through
micegene
investigations
Ventricular hypertrophy and dysfunction are exacerbated in diabetic MHC-
responsive
(Lower expression.
Left). Barsele-
63
represent mean (" SEM) BV!BW ratios (n " 7) of
and 8),atglucose
occurs serine becomes
and threoninephosphorylated
residues by hexokinase
otherwise used to
for
Analyses of H2O2 Levels and Reduced!Oxidized ments (GIRE/ChoRE)
Therefore, oneGlutathione in
or more common the
(GSH) promoter regions of these
signals must be present inmice after an injection of saline vehicle or STZ.
MHC-PPAR and NTG littermate
generate glucose
regulatory 6-phosphate.
phosphorylation. The
58 The latter
level of has multiple
cytosolic poten-
UDP-N- various glucose regulated genes, (Lower
a numberRight) Bars represent
ofheart.
candidate mean percent LV fractional shortening (n " 7 for
Ratios. Hydrogen peroxide levels (15) diabetic,
the fetal, and reduced GSH
hypertrophied, and unloaded This
each group) as assessed by echocardiographic analysis 6 weeks after an
tial fates.
acetyl These include
glucosamine, the flux
principal and
through oxidized
endthe product GSH
glycolyticof the (GSSG)
hex- levels
pathway (16)
transcriptionwere determined
factors have
common factor is most likely glucose. as
been identified
injection
that
The are believed
evidence
of vehicle or STZ.is
to
as
*, P # 0.05 vs. vehicle-injected NTG mice. **, P # 0.05
and full biosynthetic
osamine oxidation via the Krebs
pathway anddescribed.
cycle
the (or substrate
donor conversion used to be involved
follows (Figure 2).in glucose mediated gene
vs. NTGexpression.
mice and Upstream
vehicle-injected MHC-PPAR mice. (Upper) Representative
lactate),
for storageglycosylation,
protein as glycogen, entry is into
ratethelimiting
pentose phosphate
for the stimulatory factor (USF), Figure
stimulatory 4. Maldistribution
two-dimensional
protein 1 guided
(Sp1), M-mode
and of sympathetic
images of the LV obtained from the
Glucose is the primary fuel used by the fetal heart. At birth,
pathway (PPP) with concomitant Statistical Analysis.
ribose formation, Statistical
carbon comparisons
sterol were made
regulatory element by using
binding innervation
parasternal view
protein 1 in cardiac
(SREBP1) autonomiclevel
at the mid-ventricular
have neurop-
of control and diabetic NTG and
O-glycosylation of proteins (Figure 2, right). 59 Levels of increased dietary fatty
unpaired t test or ANOVA coupled to Scheffé’s test acids
when result
athy not only
(MIBG).
MHC-PPAR mice. in increased
MUGA indicates multiple
UDP-N-acetyl glucosamine are appropriate. in turn dependent All data on arethepresented as means " SEM, with a
gated acquisition scan.
TABLE 1. Fatty
uptake and metabolism Acid–Induced
of glucose, as wellGenes
statistically theand
assignificantTheir
activity Role
of in Fuel
difference Selection
defined a and Mitochondrial 0.05.Metabolism
TABLE 2. as Transcriptional
value of P #Alterations During Pressure Overload
glutamine:fructose 6-phosphate amidotransferase (GFAT),
Gene Encoding for
the rate limiting enzyme in hexosamine Results biosynthesis.60,61 Sp1
and Diabetes
Protein Function Vinik AI, Ziegler D. Circulation 2007
response independent of changes in BW, whole-cell membrane
References(C ) was used as a measure of myocyte volume in
capacitance m
Fatty acid translocase (FAT/CD36)
The Expression of the Diabetic Cardiomyopathic Phenotype Is Influ- cardiomyocytes
Hypertrophy 113, 114 Diabetes isolated from diabetic mice. Consistent with
is regulated by both reversible phosphorylation and reversible Fatty acid transport into the cell the increased BV!BW RV ,,Aritmii - b.endocrine"
ratio in diabetic PPAR!!/! martie
but not2016 in 21
enced by the Activity of PPAR!. To determine whether the
 DM - arrhythmias
•  Arrhythmias
–  ΔHRV
–  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, vention. The result
patients with diabetes mellitus may be more immobile and 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
t has been suggested that extracellular K+ ions are Table 4. Electrophysiological effects of hypokalem
Cardiology Journal 2011, Vol. 18, No. 3
equired to open the delayed rectifier channel [7].
Most– importantly,
Tissularhypokalemia alters the conduction
con- disturbances
Decrease in conduction velocity
Shortening 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 decele-
•  Apoptosis
ates. The latter effect leads to an AP with a long Early afterdepolarizations

•  Disarray
“tail”, resulting in an increase in the relative refrac-
ory period (RRP) and a decrease in the difference
–  Extracellular
of the resting membrane potential from the thresh-
Table 5. ECG manifestations of hypokalemia.
old potential • 
during
hypo-Kthe terminal
+ phase of the AP.
Thus, cardiac tissue demonstrates increased excit- Repolarization changes
–  é TDR
ability with associated ectopy for a considerable Decreased
Figure 1. Diagram of the ventricular amplitude
action potential superimposedand broadening
on the ECG at different extracellular potas
–  EAD
portion of the AP. Conduction slows because depo- trations (4.0, 3.0, 2.0
of
mEq/L).
the
The
T
numbers
waves
on the left designate the transmembrane potential in millivolts. Fro

arization begins in incompletely repolarized fibers. Prominent U waves

Furthermore, hypokalemia prolongs the plateau include: in increase inST QRSsegment
duration depression
without Hyperkalemia
a concomitant change in the QRS configuration; atrio-
he Purkinje fibers but shortens it in the ventricu-
ventricular block (AV);Tcardiac and arrest;
U waves increase fusion
in (in severe hypokalemia)
Although less common than hypok
ar fibers [12]. The AP tail of the conducting sys-
P wave amplitude and duration; and slight
Conduction abnormalities prolon- perkalemia may affect approximately 8
gation of the P–R interval. talized patients in the United States. Hy
em prolongs more than that of the ventricles, in- Increase in QRS duration is seen mainly in the setting of compro
Arrhythmogenic potential and
creasing the dispersion of repolarization. Hypokale-
clinical implications Atrioventricular
of hypokalemia
function, particularly in association with
block stration of a variety of nephrotoxic m
mia increases diastolic depolarization in Purkinje Hypokalemia-induced Cardiac arrest is clini-
hyperexcitability Hyperkalemia may result from either
cally manifested by an increase in supraventricular excretion or a shift of potassium from w
ibers, thereby increasing automaticity. and ventricular ectopy. Increase in P wave
In the Framingham Off- amplitude
(Table 6). and duration
In summary, the EP effects of hypokalemia spring Study, potassium and magnesium levels
Slight prolongation of the P-R interval
were inversely related to the occurrence of RV ,,AritmiiElectrophysiological
com- effects of hyp
- 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

 mon presentation that has previously been described in The temperature was 36.6°C, the blood pressure was 138/
literature. We presented one case of torsades de pointes due 78 mm Hg, the pulse rate was 101 beats/min, and the
to primary hyperaldosteronism. 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.
A 78-year-old
American man was
Journal of Emergency admitted
Medicine (2012) 30,to257.e5–257.e7
the hospital mask attached to a bag-valve ventilation system. On physical
because of suddenly losing his consciousness. His family examination, the pupils were 3 mm in diameter, equal, round,
had seen the patient slept 2 hours before and then saw him and reactive to light. There was no sign of trauma to the head
Scientific letters / Rev Esp Cardiol. 2012;65(5):479–488 487

www.elsevier.com/locate/ajem

Case Report

Torsade de pointes—a rare presentation of
primary hyperaldosteronism
Abstract
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
Primary aldosteronism was the most common form of
endocrine hypertension resulting in hypertension, metabolic
alkalosis, and hypokalemia. Ventricular arrhythmia in
association with primary hyperaldosteronism is an uncom-
mon presentation that has previously been described in
literature. We presented one case of torsades de pointes due
to primary hyperaldosteronism.
A 78-year-old man was admitted to the hospital
because of suddenly losing his consciousness. His family
had seen the patient slept 2 hours before and then saw him
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
verbal and physical stimulation. A patient was given a score
of 3 on the Glasgow coma scale. An electrocardiogram
obtained 5 minutes after the patient's arrival showed torsade
de pointes (Fig. 1). Spontaneous recovery within few minutes
was noted without any medications. Scientific letters / Rev Esp Cardiol. 2012;65(5):479–488
The temperature was 36.6°C, 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
mask attached to a bag-valve ventilation system. On physical
examination, the pupils were 3 mm in diameter, equal, round,
and reactive to light. There was no sign of trauma to the head

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
American Journal of Emergency Medicine (2012)
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 RV ,,Aritmii - b.endocrine" martie 2016 26
 Adrenal insufficiency - arrhythmias
011, Vol. 18, No. 3

Nabil El-She

Table 8. ECG manifestations of hyperkalemia.

Mild hyperkalemia (K = 5.5–7.5 mEq)

Tall, peaked, narrow-based T waves
Fascicular blocks (LAFB, LPFB)
Moderate hyperkalemia (K = 7.5–10.0 mEq)
d ECG is from a 74 year-old patient with a history of pacemaker implantation for sick sinus

First-degree atrioventricular block

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.

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

A I II III aVR aVL aVF

V1 V2 V3 V4 V5 V6

I II III aVR aVL aVF

C

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 Circulation March 13, 2012
Park et al Ventricular Tachycardia
e436 in Pheochromocytoma
Circulation e437
March 13, 2012

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

a hypervascular mass with central necrotic change involving the Figu
left adrenal gland (arrowhead) with lymph node metastasis in Figu
rapid
the left para-aortic space (arrow). C and D, Computed tomogra- rapid
tach
phy scans show multiple metastatic pulmonary nodules in both tach
bloc
Fig
lungs. E, The I-123 metaiodobenzylguanidine scan shows sev- bloc
B, N
rap
eral areas of abnormal uptake in the left upper posterior abdo- B,tac
tach N
men (arrowhead) and in the right lung field (arrow). F, Another tach
wasblo
region of focal uptake is visible between the previous lung was
less
B,
lesions on the follow-up scan. less
cope
tac
cope
waswa
was
nalec
les
nale
defib
cop
defib
cess
wa
cess
appr
nal
appr
defib
defi
defib
ces
app
Figure 2. A and B, Adrenal computed tomography scans show defi
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 tomogra-
phy scans show multiple metastatic pulmonary nodules in both
lungs. E, The I-123 metaiodobenzylguanidine scan shows sev-
eral areas of abnormal uptake in the left upper posterior abdo-
men (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, 82–500
!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
Acromegaly - arrhythmias - DM
• Endothelial dysfunction
• Acromegalic cardiomyopathy
•  Mechanisms - Left ventricular or biventricular hypertroph
–  Hypervolemia - Diastolic dysfunction
- Heart failure (end-stage)
–  é metabolism
• Valvular heart disease:
–  biV hypertrophy - Mitral and/or aortic annulus fibrosis/fibros
•  Diastolic disfx - Leaflet fibrosis/fibrosclerosis
- Leaflet thickening
•  Valve disease
- Calcifications
•  LVD (late) and CHF - Mitral and/or aortic regurgitation
–  DM - Aortic ectasia
• Arrhythmias:
•  Arrythmias - Ventricular ectopic beats
- Paroxysmal atrial fibrillation
–  Sinus tachycardia - Paroxysmal supraventricular tachycardia
- Sick sinus syndrome
–  Similar to other HCM - Ventricular tachycardia
(assoc. with exercise) - Bundle branch blocks
- Late potentials
RV ,,Aritmii - b.endocrine" martie 2016 31
 dle branch block
ventricular morphology,
hypertrophy, the possible presence inferior axis)
low-up.
of areas of fibrosis in the myocardium may
1A).beenTranssphenoidal
(Figure have responsible for the slowdown and surgical resec-
non-homogeneity in the propagation of action
tion of apotentials
pituitary adenoma
(2, 3) that induced had been per-
the ventricular
arrhythmias in our patient. The presence of a DISCUSSION
formed five
cochlearyears
implant previously.
contraindicated magnetic Serum levels of
resonance imaging, which might have demon-
growth hormone (GH)
strated the existence and
of areas insulin-like growth
of fibrosis. Cardiovascular disease is an important
In conclusion, careful evaluation of cardiac
factor-1 function,
(IGF-1) morphology,were 0.3
and activity and 138 ng/ml complication of acromegaly, accounting for
at diagnosis
and during follow-up appears to be essential
in the management of patients with
acromegaly. Malignant ventricular tach-
yarrhythmias 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 patient’s hands 225
Figure 2. Typical features of acromegaly in the patient apparently normal heart.

d by structural abnormalities including

rstitial fibrosis with extracellular deposi-
of 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 cardiovascu-
disease, reducing both cardiovascular mor-
Address for reprints:
Dr. Miguel A. Arias
Unidad de Arritmias y Electrofisiología Cardiaca
Hospital Virgen de la Salud, Planta Semisótano
Avda. Barber 30, 45004 Toledo, Spain
Phone: +34637463857 Fax: +34925265492
E-mail: maapalomares@secardiologia.es

Rev Port Cardiol 2011

e 3. Detail of the patient’s hands Figure 1. Twelve-lead electrocardiogram showing 225clinical ventricular tachycardia

RV ,,Aritmii - b.endocrine" martie 2016 32

Hyperparathyroidism - arrhythmias

•  êAPD è êQTc
–  VPBs
–  VF (severe & acute)
•  ST elevations
•  Ca2+ depositions:
–  AVB
–  BBB

RV ,,Aritmii - b.endocrine" martie 2016 33

Hypoparathyroidism - arrhythmias

•  éAPD è
–  é 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)

RV ,,Aritmii - b.endocrine" martie 2016 35