A Single Pathophysiological Pathway in Takotsubo Cardiomyopathy

Archives of Cardiovascular Disease (2014) 107, 245—252

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CLINICAL RESEARCH

A single pathophysiological pathway in

Takotsubo cardiomyopathy:

Catecholaminergic stress

Une seule voie physiopathologique à la cardiomyopathie de

Takotsubo : le stress catécholaminergique

a,b,1 a,b,∗,1

Elisabeth Coupez , Romain Eschalier ,

c a

Bruno Pereira , Romain Pierrard ,

a,b a,b

Géraud Souteyrand , Guillaume Clerfond ,

a a,b

Bernard Citron , Jean-René Lusson ,

d a,b

Nicolas Mansencal , Pascal Motreff

Department of Cardiology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

UMR 6284 CNRS-ISIT, Auvergne University, Clermont-Ferrand, France

Biostatistics Unit (Clinical Research and Innovation Direction), CHU de Clermont-Ferrand,

Clermont-Ferrand, France

Department of Cardiology, Université de Versailles-Saint-Quentin, Ambroise-Paré Hospital,

Centre de Référence des Maladies Cardiaques Héréditaires, Assistance Publique—Hôpitaux de

Paris, Boulogne-Billancourt, France

Received 25 January 2014; received in revised form 28 March 2014; accepted 1st April 2014

Available online 3 May 2014

KEYWORDS Summary

Takotsubo Background. — Takotsubo cardiomyopathy (TTC) continues to be under-diagnosed, due to its

cardiomyopathy; varying presentation, with potentially serious consequences if treatment is delayed.

Pheochromocytoma; Aims. — To demonstrate the consistent involvement of catecholaminergic stress in TTC, regard-

Catecholamines less of the trigger.

Methods. — Between 01 July 2009 and 31 August 2013, patients managed in our centre for

thoracic pain syndrome, with or without troponin release, were followed up prospectively.

␤

Abbreviations: +, ␤2-mimetic intoxication; CK, creatine kinase; LV, left ventricular; LVEF, left ventricular ejection fraction; PCPG,

pheochromocytoma/paraganglioma; TTC, Takotsubo cardiomyopathy.

∗

Corresponding author. Cardiology Department, Clermont-Ferrand University Hospital, 58, rue Montalembert, 63000 Clermont-Ferrand,

France.

E-mail address: [email protected] (R. Eschalier).

Elisabeth Coupez and Romain Eschalier are joint ﬁrst authors.

http://dx.doi.org/10.1016/j.acvd.2014.04.001

246 E. Coupez et al.

TTC was diagnosed from the apical ballooning seen on left ventricular imaging (angiography or

transthoracic echocardiography) in the absence of a signiﬁcant coronary artery lesion. Triggers

(emotional trauma, surgical stress and ␤2-mimetic intoxication) were recorded; catecholamine-

secreting tumours were screened for with a urinary methoxylate-derivative assay.

Results. — TTC was diagnosed in 40 out of 2754 (1.5%) patients with thoracic pain syndrome,

with or without troponin release. Triggers were emotional trauma (n = 29, 72.5%), surgical stress

(n = 5, 12.5%), adrenergic intoxication (n = 3, 7.5%) and catecholaminergic tumour (n = 3, 7.5%).

Mean left ventricular ejection fraction at admission was 38.0 ± 15.7%. Eight (20%) patients

initially showed cardiogenic shock. In-hospital mortality was 7.5%, with no deaths from car-

diogenic causes. Thirty-ﬁve (94.6%) of the survivors had recovered a normal left ventricular

ejection fraction (> 55%) by discharge.

Conclusion. — Whatever the trigger, the common denominator in TTC is catecholaminergic

stress. Classically suggested after emotional trauma, TTC may also be induced by surgical stress

␤

or endogenous or iatrogenic 2-mimetic intoxication. The various contexts all have a similarly

excellent cardiovascular prognosis if treated early.

MOTS CLÉS Résumé

Takot- Contexte. — La cardiomyopathie de Takotsubo (CTT) est sous-diagnostiquée ou tardivement du

subo cardiomyopathie ; fait des différents types de présentation pouvant conduire à des conséquences potentiellement

Phéochromocytome ; léthales.

Catécholamine Objectif. — Mettre en évidence qu’un stress catécholaminergique est l’unique voie phys-

iopathologique des CTT.

Méthodes. — Les patients hospitalisés en unité de soins intensifs pour douleur thoracique avec

ou sans libération de troponine entre le 1 juillet 2009 et le 31 août 2013 ont été suivis. Le diag-

nostic de CTT était porté devant l’aspect de ballonisation apical (ou médian/basal) du ventricule

gauche en l’absence de lésion coronaire. Les facteurs déclenchants étaient identiﬁés (stress

psychologique, contexte péri-opératoire, intoxication bêta-2 mimétique). La présence d’une

tumeur catécholaminergique était recherchée par dosage des dérivés méthoxylés urinaires.

Résultats. — Le diagnostic de CTT a été porté chez 40 patients pris en charge pour douleur

thoracique avec ou sans libération de troponine (40/2754, 1,5 %). Les facteurs déclenchants

retrouvés étaient : stress psychologique (n = 29, 72,5 %) ; péri-opératoire (n = 5, 12,5 %) ; intoxi-

cation bêta-mimétique (n = 3, 7,5 %) ; et tumeur sécrétante (n = 3, 7,5 %). La fraction d’éjection

moyenne ventriculaire gauche (FEVG) à la prise en charge était de 38,0 ± 15,7 %. La mortalité

intra-hospitalière était de 7,5 %. Trente-cinq survivants (94,6 %) avaient retrouvé une fonction

ventriculaire normale à la sortie d’hospitalisation.

Conclusions. — Peu importe le mécanisme, la décharge catécholaminergique est l’unique voie

physiopathologique de la CTT. Le stress psychologique est la description la plus classique mais

il est primordial d’évoquer ce diagnostic en cas de dysfonction ventriculaire gauche aiguë dans

un contexte péri-opératoire, d’intoxication au beta-mimétique et de rechercher la présence

d’une tumeur sécrétante de catécholamines.

Background (release of troponin and creatine kinase [CK]) [6]. Imag-

ing (transthoracic echocardiography, left ventricular [LV]

Takotsubo cardiomyopathy (TTC) is a rare, but potentially angiography or cardiac magnetic resonance imaging) shows

severe, disease [1,2] that was ﬁrst deﬁned in 1990 [3]. Sev- transient LV dysfunction; the regional wall motion abnormal-

eral retrospective studies have estimated that 0.7—4.9% of ities extend beyond a single epicardial vascular distribution

patients presenting with suspected acute coronary syndrome (apical ballooning with an octopus trap [Japanese: takot-

have TTC [4], and its incidence is estimated to be 29.8 per subo] pattern). Coronary angiography rules out signiﬁcant

1,000,000 inhabitants in a global population [4,5]. Classi- coronary artery stenosis [6] and normal LV systolic function

cally, diagnosis is considered in cases of emotional trauma is usually recovered within a few weeks [7,8].

[3]. The pathophysiology of TTC remains controversial.

The clinical presentation of TTC may mimic acute coro- Epicardial coronary spasm [9—11], atheromatous plaque

nary syndrome, generally involving chest pain, new electro- rupture [12], myocarditis [13] or infarction with healthy

cardiographical abnormalities and biological abnormalities coronaries [14] have been suggested, but are now dismissed

Takotsubo pathophysiology 247

[15]. Catecholaminergic stress following emotional trauma normality veriﬁed by the Shapiro—Wilk test and homoscedas-

is presently the hypothesis of choice [9,16]. However, the ticity by the Fisher—Snedecor test. Owing to sample size,

current Mayo Clinic criteria [6] require catecholamine- non-parametric tests were often preferred. Considering the

secreting tumour to be ruled out for a diagnosis of TTC. sample size and univariate results, no multivariable analysis

The aim of the present study was to demonstrate was considered. Finally, to study the evolution of variables

the major involvement of catecholaminergic stress in TTC at several time points, mixed models, taking into account

induced by different triggers. within and between subject variability, were considered.

Methods Results

Between 01 July 2009 and 31 August 2013, patients man- Study population characteristics

aged in our centre for chest pain syndrome and/or troponin

release were followed up. TTC was diagnosed exclu- Between 01 July 2009 and 31 August 2013, 2754 patients

sively from an LV angiographical or echocardiographical were admitted to our centre for chest pain, with or without

pattern of apical (typical TTC) or medial or basal balloon- troponin release. A diagnosis of TTC was conﬁrmed in 40

ing [17] (medial or inverse TTC) [6] without signiﬁcant patients (40/2754, 1.5%; Fig. 1). Medical care was initiated

coronary lesions on angiography. Left ventricular ejection at a mean of 9.8 6.2 hours after symptom onset.

fraction (LVEF) was measured on LV angiography (Axiom History-taking found acute adrenergic stress concomi-

Sensis XP; Siemens, Erlangen, Germany) and/or echocar- tant with symptom onset: emotional trauma (29/40, 72.5%:

diography using the Simpson biplane method (Vivid E9; including family death [11/29, 37.9%] and physical aggres-

GE-Vingmed, Horten, Norway). Tw o experienced blinded sion [3/29, 10.3%]), surgery (5/40, 12.5%: two ears, nose

operators analysed segmental kinetics retrospectively from and throat/bronchopulmonary carcinoma resections, one

DICOM recordings. laparoscopic hernia operation, one carotid endarterectomy

Data were collected on history, cardiovascular risk fac- and one kidney transplant) and adrenergic intoxication

␤

tors and context of onset (emotional trauma, surgical stress (3/40, 7.5%: two overdoses of 2-mimetics for acute

␤

or 2-mimetic intoxication [␤+]). asthma and one voluntary intoxication by intravenous

From 01 September 2011, all patients (19/40) under- adrenalin injection). These last three patients (adrener-

went complementary screening for catecholamine-secreting gic intoxication) were female (aged 27, 60 and 66 years,

tumour (pheochromocytoma/paraganglioma [PCPG]) by respectively), with a cardiogenic shock presentation for the

urinary methoxylate-derivative high-performance liquid youngest (voluntary intoxication by intravenous adrenalin

chromatography assay (Chromsystems GmbH, Munich, injection). Interestingly, in three (7.5%) patients, elevated

Germany) within the ﬁrst 3 days and thoracic-abdominal- urinary methoxylate-derivative concentrations enabled the

pelvic computed tomography or methoxy-isobutyl-isonitrile diagnosis of a catecholamine-secreting tumour (one para-

scintigraphy. Three measurements of 24-hour urinary ganglioma and two pheochromocytomas) leading to TTC,

methoxylate-derivative concentrations were taken during conﬁrmed by thoracic-abdominal-pelvic computed tomo-

the ﬁrst 3 consecutive days after admission. graphy or methoxy-isobutyl-isonitrile scintigraphy. These

The characteristics of the overall population and various three patients (two women and one man, aged 65, 50

groups were studied according to trigger mechanism: emo- and 41 years, respectively) did not exhibit any symp-

tional trauma, surgical stress, PCPG or ␤+. Clinical follow-up toms of catecholamine-secreting tumour (no hypertension,

comprised functional and therapeutic assessment at 1, 3 and headaches or palpitations) before the diagnosis of TTC.

12 months. Patients with TTC due to emotional trauma were older

± ±

LVEF was assessed by echocardiography and/or LV angiog- (68.9 11.7 vs 58.5 14.4 years; P = 0.05) and more were

raphy at initial assessment, and by echocardiography at 7 female (29/29 [100%] vs 6/11 [54.5%]; P = 0.001) compared

␤

days, 1 month and 12 months after onset. Troponin and with patients in the three other groups (surgery, + and

CK concentrations were measured during the initial hospi- PCPG). TTC characteristics are shown in Table 1.

tal stay at several time points after TTC onset (6, 12, 24, Tw o cases were of recurrence (one emotional trauma and

48 and 72 hours). Only peak CK and troponin concentrations one PCPG), at intervals of 3 months and 4 years, respec-

are presented. tively, after complete recovery.

There were immediate non-speciﬁc electrocardiograph-

Statistical analysis ical abnormalities in 27 (67.5%) patients: ST-segment and

T-wave abnormalities and presence of Q wave; the other 13

Statistical analysis was performed using Stata software, patients had normal electrocardiograms.

version 12 (StataCorp, College Station, TX, US). The tests

␣

were two-sided, with a type I error set at = 0.05. Base- Biological characteristics

line characteristics are presented as the mean ± standard

deviation or median (interquartile range) for each group for We observed increased peak concentrations of CK

continuous data and as the number of patients and associ- and troponin in all patients (40/40). The mean tro-

ated percentages for categorical variables. These variables ponin I peak concentration was 3.89 ± 6.1 ␮g/L (range

were compared between groups using the Chi or Fisher’s 0.071—30.5 ␮g/L [normal range 0.015—0.045 ␮g/L]) and

exact test for categorical variables and Student’s t test mean CK peak concentration was 687.3 ± 1587.0 ␮g/L

or the Mann—Whitney test for quantitative variables, with (range 96—6461 ␮g/L [normal range 39—308 ␮g/L]).

248 E. Coupez et al.

Figure 1. Flowchart of study patients. ␤+: ␤-mimetic intoxication; LV: left ventricle; PCPG: pheochromocytoma/paraganglioma; TTC:

Takotsubo cardiomyopathy; TTE: transthoracic echocardiography.

Nineteen patients had urinary methoxylate-derivative

screening. The mean urinary metanephrine concentration

was 2.28 ± 8.29 ␮mol/24 hours (emotional trauma 0.32

1.7 ␮mol/24 hours; surgical stress 0.65 ± 0.56 ␮mol/24

hours; ␤+ 0.41 ± 0.25 ␮mol/24 hours; PCPG 15.07 ± 19.8

␮

mol/24 hours) (normal range < 4.4 ␮mol/24 hours).

The mean urinary normetanephrine concentration was

2.40 ± 3.55 ␮mol/24 hours (emotional trauma 1.63 ± 0.8

␮

mol/24 hours; surgical stress 2.66 ± 0.73 ␮mol/24 hours;

␤

+ 1.62 ± 0.54 ␮mol/24 hours; PCPG 7.03 ± 8.9 ␮mol/24

hours) (normal range < 2.2 ␮mol/24 hours).

The mean total urinary metanephrine concentration was

4.68 ± 11.69 ␮mol/24 hours (emotional trauma 1.95 ±

0.93 ␮mol/24 hours; surgical stress 3.31 ± 1.28 ␮mol/

24 hours; ␤+ 2.04 ± 0.63 ␮mol/24 hours; PCPG 22.1 ±

28.4 ␮mol/24 hours) (normal range < 5.5 ␮mol/24 hours)

(Fig. 2).

The mean urinary concentrations of metanephrine,

Figure 2. Urinary metanephrine concentrations.Mean urinary

normetanephrine and total metanephrine were higher in the

metanephrine, normetanephrine and total metanephrine concen-

PCPG group than in the other groups (emotional trauma,

trations were in the normal ranges in emotional trauma, surgery

surgery and ␤+) (P < 0.05).

and ␤-mimetic intoxication situations. However, these three varia-

bles were higher in pheochromocytoma/paraganglioma (PCPG) than

Imaging characteristics in these other situations and were above the normal ranges.

Imaging (echocardiography [35/40, 87.5%] and/or LV angiog-

raphy [15/40, 37.4%]) was performed in the cardiological Evolutions of mean LVEF are presented in Table 2. Most

care unit within 3 hours of admission in all patients. Coro- patients (n = 35, 80.0%) presented with a typical TTC pat-

nary artery angiography (n = 40, 100%) found no signiﬁcant tern (Fig. 3) [6]. The ﬁve atypical forms (four medial and one

lesions. inverse TTC) were all secondary to emotional trauma. All the

Takotsubo pathophysiology 249

Table 1 Population characteristics.

All patients Emotional trauma Surgical stress ␤+ (n = 3; 7.5%) PCPG (n = 3; 7.5%)

(n = 40; 100%) (n = 29; 72.5%) (n = 5; 12.5%)

Mean age (years) 65.0 ± 13.0 67 ± 11.9 63.5 ± 1.7 51 ± 21 56.5 ± 9.2

Men/women 6/34 0/29 4/1 0/3 2/1 (n/n)

CVRFs

Hypertension 17 (42.5) 14 (48.3) 2 (40.0) 0 1 (33.3)

Smoking 12 (30.0) 8 (27.6) 2 (40.0) 1 (33.3) 1 (33.3)

Diabetes 3 (7.5) 3 (10.3) 0 0 0

Dyslipidaemia 6 (15.0) 5 (17.4) 1 (20.0) 0 0

Familial history 5 (12.5) 4 (13.8) 0 0 1 (33.3)

of CAD

Overweight 8 (20.0) 7 (24.1) 0 1 (33.3) 0

(BMI > 25 kg/m ) Previous

treatment

Beta-blockers 5 (12.5) 5 (17.5) 0 0 0

CCBs 7 (17.5) 4 (13.8) 2 (40.0) 1 (33.3) 0

ACEIs 3 (7.5) 3 (10.3) 0 0 0 Clinical

presentation

Chest pain 28 (70.0) 25 (86.2) 0 2 (66.7) 1 (33.3)

APO 4 (10.0) 4 (10.0) 0 0 0

Cardiogenic 8 (20.0) 1 (3.4) 5 (100) 1 (33.3) 1 (33.3)

shock

History of TTC 2 (5.0) 1 (3.4) 0 0 1 (33.3)

Forms of TTC (n)

Typical 35 24 5 3 3

Median 4 4 0 0 0

Inverse 1 1 0 0 0

Data are mean ± standard deviation or number (%), unless otherwise indicated. ACEI: angiotensin-converting enzyme inhibitor; APO:

acute pulmonary oedema; ␤+: ␤-mimetic intoxication; BMI: body mass index; CAD: coronary artery disease; CCB: calcium chan-

nel blockers; CVRF: cardiovascular risk factor; F: female; M: male; PCPG: pheochromocytoma/paraganglioma; TTC: Takotsubo

cardiomyopathy.

␤

perioperative, +-related and PCPG-related forms showed a In-hospital management

typical TTC pattern. There was no difference in imaging TTC

presentation between emotional trauma patients and other Nine (22.5%) patients required vasopressor amine support:

patients (P = 0.20); however, emotional trauma patients pre- adrenaline (n = 1, 2.5%); milrinone (n = 1, 2.5%); noradrena-

sented with a higher initial LVEF than other patients (42 14 line (n = 7), 17.5%; dobutamine (n = 4, 10.0%). Four patients

vs 29 17%; P = 0.01). (10.0%) required mechanically assisted circulation with

One emotional trauma patient experienced recurrence of extracorporeal membrane oxygenation for a mean of 3 ± 2

TTC during follow-up: the primary episode was typical TTC, days. Invasive mechanical ventilation was implemented in

with complete recovery and the second was inverse TTC. four patients (10.0%) for a mean of 7 ± 2 days. During

Table 2 Left ventricular ejection fraction follow-up of patients presenting with Takotsubo cardiomyopathy.

All patients Emotional trauma Surgical stress ␤+ (n = 3) PCPG (n = 3)

(n = 40) (n = 29) (n = 5)

Initial LVEF (%) 38.0 ± 15.7 40.1 ± 13.5 15.0 ± 5 52.0 ± 18.2 29.5 ± 0.7

LVEF at 7 days (%) 55.9 ± 10.7 53.6 ± 11.1 56.0 ± 1.73 70.3 ± 4.0 55.0 ± 3.5

LVEF at 1 month (%) 57.3 ± 3.7 57.4 ± 4.14 57.4 ± 2.7 56.0 ± 0.3 55.5 ± 0.7

LVEF at 1 year (%) 59.3 ± 3.6 60.2 ± 4.1 56.5 ± 2.1 58.3 ± 2.9 61.5 ± 9.2

Data are mean ± standard deviation. ␤+: ␤-mimetic intoxication; LVEF: left ventricular ejection fraction; PCPG: pheochromocytoma/paraganglioma.

250 E. Coupez et al.

Figure 3. Angiographic pattern of left ventricle typical Takotsubo cardiomyopathy. Typical left ventricle apical ballooning with an octopus

trap, with left ventricular ejection fraction (EF) of 45%.

the ﬁrst 48 hours, angiotensin-converting enzyme inhibitors hypothesis of catecholaminergic stress inducing acute LV

were prescribed in 23 (57.5%) cases, ␤-blockers in 13 (32.5%) dysfunction [13,18,19], which has been shown by the present

␣

cases and -blockers in three (7.5%) cases. The mean stay study to be consistently involved in varying clinical situations

in the cardiological care unit was 7.1 6.7 days. (Fig. 4).

Previous pathophysiological hypotheses have been ruled

Evolution out by the most recent ﬁndings. The hypothesis of myocardi-

tis was ruled out by myocardial biopsy results and was

Haemodynamic evolution was favourable in all cases. LVEF further conﬁrmed by more recent magnetic resonance

improved as of day 7 (Table 2).

However, three (7.5%) patients in the surgical stress

group died (D8, D17, D22) of surgery or intensive care

complications (nosocomial infections for two patients

and invasive mechanical ventilation complication for one

patient) after complete recovery of LVEF (> 55%). There was

no difference in terms of LVEF between emotional trauma

patients and other patients at month 1 (57 ± 4 vs 57 ± 2;

P = 0.62) and month 12 (59 ± 8 vs 60 ± 6; P = 0.46).

After a mean follow-up of 23 ± 15 months, 37/40 (92.5%)

patients were alive and free of symptoms, with a mean

LVEF of 59.3 ± 3.6%. Most surviving patients (n = 35, 94.6%)

showed normal LV systolic function (LVEF > 55%) at discharge;

36 (97.3%) showed normal LV systolic function by 1 month.

Discussion

The pathophysiology of TTC has been controversial ever

Figure 4. Pathophysiology of Takotsubo cardiomyopathy: from

since the disease was ﬁrst described [10] but is steadily adrenergic inundation to myocardial stunning. PCPG: pheochromo-

becoming less so. Several authors have agreed on the cytoma/paraganglioma.

Takotsubo pathophysiology 251

imaging ﬁndings of no signs of myocarditis [20]. The hypoth- Even in cases of identiﬁable exogenous stress,

esis of epicardial coronary spasm was put forward [10], but catecholamine-secreting tumour should be screened

ergonovine-induced spasm tests proved positive in only 14% for. Indeed, pheochromocytoma and paraganglioma have

of cases in the study by Abe et al. [9]. The hypothesis of an estimated incidence of 10 per million in the general

healthy coronary infarction was soon abandoned [12], as population [31]. However, the present study conﬁrmed

evolution tends toward complete recovery of LV function, that the incidence is signiﬁcantly higher in patients with

without myocardial necrotic sequelae on echocardiography TTC (7.5%), as described in some case reports [32]. In the

or cardiac magnetic resonance imaging. present cohort, a pheochromocytoma was discovered in a

The involvement of the adrenergic cascade is presently patient presenting with TTC following emotional shock (her

the hypothesis of choice [13]: physical or emotional stress husband’s funeral). A simple urinary methoxylate-derivative

␤

inundates myocardial -receptors, stunning the left ventri- assay can detect most actively-secreting catecholaminergic

cle. Blood catecholamine concentrations are higher in TTC tumours [33], as we demonstrated that the concentrations

patients than in Killip class III myocardial infarction patients were higher in such patients compared with in other

[21]. Anatomopathological biopsy ﬁnds disorganized cell groups.

architecture (hypertrophied myocytes, intracytoplasmic

areas ﬁlled with glycogen, reduced amount of contractile

Study limitations

protein actin) without apoptosis [21]. The distribution of

␤

myocardial receptors [22] (a majority of ␤2 receptors at

The limitations of the present study should be noted. The

the apex, with a negative inotropic effect; a majority of

sample only comprised 40 patients, although the incidence

␤

norepinephrine-sensitive 1 receptors in basal segments,

was similar to that in previous reports [6], and this was

with a positive inotropic effect) suggests the consistent

one of the largest prospective series published for an entity

involvement of catecholaminergic stress, whatever the ini-

that is still recent. The favourable spontaneous evolution of

tial trigger.

minor forms suggests that some cases may be undiagnosed,

Various causes of endogenous or exogenous stress (epilep-

especially in perioperative situations. Conversely, over the

tic seizure [23], surgery [24], meningeal haemorrhage

study period, the frequent use of the troponin assay and

[25,26], synephrine dietary supplements [27], hanging [28]

systematic very early coronary artery and LV angiography in

and severe emotional stress [6]) or massive consumption

case of myocardial infarction with non-ST segment elevation

␤

of 2-mimetics saturate myocardial 2 receptors, stunning

corrected such underestimation. We did not perform any

affected segments and inducing myocardial stunning that is

measurements of urinary metanephrin and normetanephrin

relieved by clearance of the sympathetic receptors. Under-

concentrations in patients managed in our intensive care

lying all these situations is thus sudden major endogenous

unit for chest pain without TTC, although several stud-

or exogenous catecholaminergic stress [29].

ies have evaluated this point, with several discrepancies

Studies are presently underway to analyse patients’

[21,34,35]. Finally, owing to the sample size, a lack of power

genetic predisposition to TTC, in terms of allele vari-

had to be conceded for statistical analysis.

ability and gene expression of catecholaminergic pathway

receptors, regulators and transducers (TAKOGENE study,

NCT01520610).

Although presentation may be extremely serious, Conclusions

haemodynamic prognosis is favourable overall [6]. In the

present cohort, there were no deaths due to LV systolic The acute left ventricular systolic dysfunction characteriz-

dysfunction and LVEF recovered completely (> 55%) in ing TTC consistently involved myocardial catecholaminergic

94.6% of surviving patients by discharge and in 97.3% by 1 stress, regardless of the underlying mechanism. Although

month. emotional shock is classically involved, it is essential to rule

Vasopressor amine support in our study was used before out catecholamine-secreting tumour (pheochromocytoma,

TTC diagnoses were made in a cardiogenic shock situa- paraganglioma). Haemodynamic instability in the perioper-

␤

tion in the majority of cases. After TTC diagnoses were ative period or in patients treated with 2-mimetics may

made, vasopressor amine support was stopped, which may also suggest TTC. The demonstration of this single patho-

explain the total recovery of this population. Some of physiological mechanism should allow early diagnosis and

these presentations may lead to misdiagnosis, especially in adapted treatment, usually enabling complete recovery of

the surgical situation [30], where onset of haemodynamic LV function.

instability primarily suggests anaphylactic shock. Failure

to obtain rapid response to vasopressors is an indica-

tion for perioperative echocardiography. Adrenergic drugs,

Disclosure of interest

however, could aggravate stunning if TTC has not been diag-

nosed.

The authors declare that they have no conﬂicts of interest

Medical management of the subacute phase relies on ␤-

concerning this article.

receptor blockers to maximize relief of adrenergic stress in

the affected myocardial segments, but also on angiotensin-

converting enzyme inhibitors to enhance LV recovery. Given

the risk of recurrence, however low (2/40 [5%] cases in the Acknowledgments

present series), long-course ␤-blockers should be consid-

ered. We thank Mr. Iain McGill for the editing of this manuscript.

252 E. Coupez et al.

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