Scared to Death

Abstract

Myocardial infarction with nonobstructed coronary arteries (MINOCA) can be triggered by intense emotions. We report 5 cases of emotional stress–related death where forensic examination attributed myocardial infarction to a coronary spasm, with the ultimate cause of death being arrhythmias in 4 cases and cardiac rupture in the fifth. (Level of Difficulty: Beginner.)

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MINI-FOCUS ISSUE: INTERVENTIONS
CASE REPORT: CLINICAL CASE SERIES
Scared to Death
Emotional Stress Causing Fatal Myocardial Infarction With
Nonobstructed Coronary Arteries in Women
Alberto Aimo, MD,
a,b
Marco Di Paolo, MD,
c
Vincenzo Castiglione, MD,
a,b
Martina Modena, BS,
a
Andrea Barison, MD, PHD,
a,d
Matteo Benvenuti, MD,
c
Valentina Bugelli, MD,
c
Carlo Pietro Campobasso, MD,
c
Benedetta Guidi, MD,
c
Paolo G. Camici, MD, PHD,
e
Michele Emdin, MD, PHD
a,e
ABSTRACT
Myocardial infarction with nonobstructed coronary arteries (MINOCA) can be triggered by intense emotions. We report
5 cases of emotional stress–related death where forensic examination attributed myocardial infarction to a coronary
spasm, with the ultimate cause of death being arrhythmias in 4 cases and cardiac rupture in the fifth. (Level of Dif-
ficulty: Beginner.) (J Am Coll Cardiol Case Rep 2020;2:2400–3) © 2020 The Authors. Published by Elsevier on
behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
The acronym MINOCA (myocardial infarction
with nonobstructed coronary arteries) de-
fines a condition in which clinical evidence
of myocardial infarction (MI) is associated with angio-
graphically normal or nearly normal coronary arteries
(stenosis <50%) (1). MINOCA is 3 times more frequent
among women and accounts for approximately 6% of
cases of MI, with a prognosis similar to that of
“obstructive”(type1)MI(2). Patients may die during
theacutephaseofMINOCA,andalthoughwearenot
aware of any specific analysis of the causes of death in
this setting, it is reasonable to assume that death may
result from ventricular arrhythmias or mechanical
complications of transmural MI (in patients with
longer survival after symptom onset), as in type 1
MI. An intense emotion may cause a MINOCA,
possibly through an intense catecholamine release
in the myocardium, which may trigger a coronary ar-
tery spasm or directly induce cardiomyocyte necrosis
with a typical histological appearance of contraction
band necrosis (3). Here we report 5 cases of fatal MI
that were classifiable as MINOCA and that occurred
after an intense emotion. These cases were identified
from a systematic search of all forensic examinations
performed over a 10-year time span at a single univer-
sity hospital (University Hospital of Pisa).
CASE DESCRIPTIONS
CASE 1. A 46-year-old woman was found dead in her
bed by her husband the morning after a violent
LEARNING OBJECTIVES
To learn that sudden cardiac death can occur
shortly after an intense emotion.
To understand the plausible mechanisms
underlying this phenomenon.
To learn the findings on forensic
examination.
ISSN 2666-0849 https://doi.org/10.1016/j.jaccas.2020.08.010
From the
a
Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy;
b
Cardiology Division, University Hospital of Pisa, Pisa,
Italy;
c
Department of Forensic Medicine, University of Pisa, Pisa, Italy;
d
Cardiology Division, Fondazione Toscana Gabriele
Monasterio, Pisa, Italy; and the
e
Cardiology Division, Vita Salute University and San Raffaele Hospital, Milan, Italy.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.
Manuscript received May 14, 2020; revised manuscript received August 7, 2020, accepted August 14, 2020.
JACC: CASE REPORTS VOL. 2, NO. 15, 2020
ª2020 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN
COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER
THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/).

altercation between them. At autopsy, a large area of
contraction band necrosis was present within the left
ventricular (LV) free wall, although the epicardial
coronary arteries did not display any significant
stenosis.
CASE 2. A 71-year-old woman was tied up during a
home invasion robbery and was found dead shortly
afterward. At autopsy, the only pathological finding
was extensive contraction band necrosis in the sub-
endocardial region of the LV free wall.
CASE 3. An 85-year-old woman was the victim of a
robbery. She called her neighbors for help, but a few
minutes later she reported chest pain and lost con-
sciousness. On first medical contact, the patient was
in cardiac arrest, and resuscitation maneuvers were
unsuccessful. Forensic examination demonstrated an
extensive area of transmural contraction band ne-
crosis in the LV free wall, with a few coronary artery
stenoses <50% in the left anterior descending and
circumflex arteries.
CASE 4. An 82-year old woman was tied to a chair
during a home invasion robbery and was found dead
in that position. Forensic examination showed sub-
endocardial contraction band necrosis in the antero-
lateral region of the left ventricle, with coronary
artery stenoses <50% in the circumflex and right
coronary arteries.
CASE 5. An 86-year-old woman was robbed in the
castle where she lived alone. She was dragged on the
floor by her hair and forced to reveal the location of
the safe. Approximately 1 h later, while reporting the
theft, she reported intense retrosternal chest pain and
was brought to the emergency department. The
electrocardiogram showed marked ST-segment
elevation in leads V
2
to V
6
, and high-sensitivity
troponin T (hs-TnT) levels were increased (106 ng/l
[reference value <14 ng/l]). A transthoracic echocar-
diogram demonstrated an akinetic area in the mid-
cavity and apical portion of the anterior LV wall,
together with hypokinesia of the remaining distal
segments. Coronary angiography was performed
approximately 2 h after symptom onset and showed
only 2 nonsignificant stenoses (both <30%) in the
right coronary artery (Figure 1A). The patient
remained stable and asymptomatic over the next
2 days, with modestly raised hs-TnT (660 ng/l on the
first day and 380 ng/l on the second day). Follow-up
echocardiograms showed hypokinetic LV distal seg-
ments. On the third day, the patient died suddenly of
cardiac arrest refractory to resuscitation maneuvers.
Post-mortem examination revealed a full-
thickness rupture in the distal portion of the
anterior LV wall that caused pericardial tam-
ponade (Figures 1B and 1C). Around the
rupture, histological examination demon-
strated an area of transmural myocardial ne-
crosis, in full accordance with an MI
occurring a few days earlier (Figure 1D). The
absence of significant coronary artery steno-
ses was confirmed.
DISCUSSION
In the first 4 cases, the diagnosis of MI was made
during autopsy, and the only significant pathological
finding on forensic examination was an area of
myocardial necrosis, either subendocardial or trans-
mural. In these cases, a malignant ventricular
arrhythmia elicited by myocardial ischemia or ne-
crosis could be assumed to be the direct cause of
death. In contrast, the fifth patient died 3 days after a
clinical diagnosis of MINOCA because of cardiac
rupture related to extensive, transmural necrosis,
with echocardiographic evidence of diffuse hypo-
kinesis of distal segments, compatible with an
initial form of takotsubo cardiomyopathy (Table 1).
In all cases, a working diagnosis of MINOCA was
made according to the diagnostic criteria proposed
by the European Society of Cardiology (1), whereas
the American Heart Association considers takotsubo
syndrome to be a separate entity from MINOCA (4).
Patients either had no coronary artery stenoses
(Cases 1 and 2) or <50% stenoses (Cases 3, 4, and 5).
Given that no evident cause of oxygen supply-
demand imbalance (e.g., plaque rupture or erosion,
thromboembolism, coronary dissection) emerged, the
MI events could be most likely attributed to an
emotional stress–induced epicardial or microvascular
spasm. Notably, an embolic cause of the MI could not
be completely ruled out in these cases, but it seemed
very unlikely because no evidence of embolic mate-
rial was found in the coronary arteries.
An intense emotion may trigger a MINOCA, as
suggested by a study where 76% of patients with
MINOCA reported an emotional stress, compared with
only 32% of patients with MI secondary to coronary
obstruction (5). In this study, when cases of takotsubo
syndrome were excluded, 17% of patients with
MINOCA reported an acute emotional distress versus
6% of patients with “obstructive”MI (5).
Spasm of the epicardial coronary arteries and/or
intramural arterioles is a common pathogenic
ABBREVIATIONS
AND ACRONYMS
hs-TnT =high-sensitivity
troponin T
LV =left ventricular
MI =myocardial infarction
MINOCA =myocardial
infarction with nonobstructed
coronary arteries
JACC: CASE REPORTS, VOL. 2, NO. 15, 2020 Aimo et al.
DECEMBER 2020:2400–3Fatal Stress-Related MINOCA
2401

mechanism in MINOCA and has been found on pro-
vocative testing in 27% of these patients (6). Coronary
artery spasm is defined as total or subtotal (>90%)
coronary artery occlusion, with ischemic electrocar-
diographic changes occurring either spontaneously or
in response to a provocative stimulus (7). Coronary
artery spasm is generally transient, causing Prinz-
metal angina, but occasionally it may be sufficiently
prolonged to induce an MI (8). Endothelial dysfunc-
tion, abnormal regulation of myofibril contraction,
and reduced parasympathetic tone are all possible
causes of vascular hyperreactivity. On this substrate,
macrovascular or microvascular spasm may be eli-
cited by sudden surges of sympathetic activity, as in
the case of intense emotions (4)orexogenoussub-
stances (e.g., methamphetamines or cocaine).
Emotional triggers could also promote cardiac elec-
trical instability and increase the risk of ventricular
arrhythmias, and possibly cardiac arrest, following
myocardial ischemia and necrosis. The possibility of a
stress-related trigger of MINOCA is also corroborated
by the circadian and circaseptan variations in its
onset, with an increased risk in the early morning and
on Mondays (9).
Another possible mechanism of cardiomyocyte
necrosis, not mutually exclusive with epicardial or
microvascular spasm, is a local increase in catechol-
amines, following a sudden increase in sympathetic
outflow to the heart (4). The same mechanisms could
explain the development of the specificformof
MINOCA known as takotsubo syndrome, which is also
elicited by intense emotions and typically develops in
middle-aged or older women (10). A disease contin-
uum can be postulated, ranging from local car-
diomyocyte necrosis triggering fatal arrhythmias to
more extensive damage leading to the alterations of
FIGURE 1 Fatal Transmural Myocardial Infarction Without Significant Coronary Artery Stenoses
Case 1. (A) Coronary angiography showing no significant stenoses in the right coronary artery (left) or the left anterior descending and
circumflex arteries (right). (B and C) Full-thickness rupture in the distal portion of the left ventricular anterior wall. (D) Cardiomyocyte
necrosis with red blood cell and neutrophil infiltrates (hematoxylin and eosin stain, original magnification 20).
Aimo et al.JACC: CASE REPORTS, VOL. 2, NO. 15, 2020
Fatal Stress-Related MINOCA DECEMBER 2020:2400–3
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LV geometry and function characteristic of takotsubo
syndrome. Cardiac rupture in the setting of takotsubo
syndrome is an extremely rare phenomenon, and
only approximately 20 cases showing this association
have been reported (11). When the first clinical
manifestation is not sudden cardiac death, an effort
should be made to elucidate the pathophysiology of
MINOCA to provide therapies targeting disease
mechanisms, for example, antispastic agents such as
calcium channel blockers or nitrate when epicardial
coronary vasospasm is believed to be the underlying
cause (4). Furthermore, modulation of the neuro-
hormonal response to stress holds some promise,
and an ongoing trial is evaluating the potential
benefit of angiotensin-converting enzyme inhibitors
and angiotensin receptor blockers in MINOCA
(Randomized Evaluation of Beta Blocker and Angio-
tensin Converting Enzyme Inhibitor /Angiotensin
Receptor Blocker Treatment in MINOCA Patients;
NCT03686696).
CONCLUSIONS
Fatal MINOCA may occur shortly after an intense
emotion. We report 5 cases where forensic examina-
tion established a diagnosis of MI and attributed it to
a coronary macrovascular or microvascular spasm,
with the ultimate cause of death being arrhythmias in
4 cases and LV free wall rupture in the fifth.
AUTHOR DISCLOSURES
The authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
ADDRESS FOR CORRESPONDENCE: Dr. Michele
Emdin, Scuola Superiore Sant’Anna and Fondazione
Toscana Gabriele Monasterio, Via G. Moruzzi 1, 56124
Pisa, Italy. E-mail: emdin@ftgm.it.ORm.emdin@
santannapisa.it.
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KEY WORDS emotional stress, forensic
examination, MINOCA, myocardial infarction
TABLE 1 Timeline
Event Case1 Case2 Case3 Case4 Case5
Event type Altercation Robbery Robbery Robbery Robbery
Time of day of the event Evening Evening Evening Evening Evening
Death ? ? w1 h after the robbery ? 3 days after coronary angiography
Body found Day after (morning) Around 3 h after the robbery —Day after (morning) —
Likely cause of death Ventricular arrhythmia Ventricular arrhythmia Ventricular arrhythmia Ventricular arrhythmia Left ventricular wall rupture
JACC: CASE REPORTS, VOL. 2, NO. 15, 2020 Aimo et al.
DECEMBER 2020:2400–3Fatal Stress-Related MINOCA
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