Sie sind auf Seite 1von 16

Accepted Manuscript

Title: Cardiovascular causes of maternal sudden death. Sudden


Arrhythmic Death Syndrome is leading cause in UK

Author: Dimitra Krexi Mary N. Sheppard

PII: S0301-2115(17)30109-4
DOI: http://dx.doi.org/doi:10.1016/j.ejogrb.2017.03.006
Reference: EURO 9810

To appear in: EURO

Received date: 6-1-2017


Revised date: 27-2-2017
Accepted date: 4-3-2017

Please cite this article as: Krexi D, Sheppard MN, Cardiovascular causes of
maternal sudden death. Sudden Arrhythmic Death Syndrome is leading cause in UK,
European Journal of Obstetrics and Gynecology and Reproductive Biology (2017),
http://dx.doi.org/10.1016/j.ejogrb.2017.03.006

This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.
Cardiovascular causes of maternal sudden death. Sudden Arrhythmic Death

Syndrome is leading cause in UK

Dimitra Krexi, Mary N Sheppard*msheppar@sgul.ac.uk

t
ip
Cardiac Risk in the Young, Department of Cardiovascular Pathology,

cr
Cardiovascular Sciences Research Centre, St George’s University of London,

London, United Kingdom

us
an
* Corresponding author. Cardiac Risk in the Young Department of

Cardiovascular Pathology, Cardiovascular Sciences Research Centre, Jenner


M
Wing, Floor 1 Cranmer Terrace St George’s University of London, London,

SW17 0RE, UK, Tel. 02087255959, fax 0208725 5139


d
te

Abstract
p

Objective This study aims to determine the causes of sudden cardiac death
ce

during pregnancy and in the postpartum period and patients’ characteristics.

There are few studies in the literature


Ac

Methods 80 cases of sudden unexpected death due to cardiac causes in

relation to pregnancy and postpartum period in a database of 4678 patients

were found and examined macroscopically and microscopically.

Results The mean age was 30±7 years with a range from 16 to 43 years. 30%

were 35 years old or older. 50% of deaths occurred during pregnancy and

50% during the postpartum period. 59.18% were obese or overweight where

1
Page 1 of 15
Body Mass Index data were available. The leading causes of death were

Sudden Arrhythmic Death Syndrome (SADS) (53.75%) and cardiomyopathies

(13.80%). Other causes include dissection of aorta or its branches (8.75%),

congenital heart disease (2.50%) and valvular disease (3.75%).

t
Conclusion This study highlights sudden cardiac deaths in pregnancy or in the

ip
postpartum period, which is mainly due to SADS with underlying

cr
channelopathies and cardiomyopathy. We wish to raise awareness of these

frequently under-recognised entities in maternal deaths and the need of

us
cardiological screening of the family as a result of the diagnosis.

Keywords
an
M
Sudden cardiac death, Cardiovascular maternal death, Sudden Arrhythmic

Death Syndrome (SADS), Cardiomyopathy, Cardiological screening


d
te

INTRODUCTION
p

There has been a decline of maternal mortality over the past decades in the
ce

western world (1) but maternal deaths are still the most common cause of
mortality among women of reproductive age(2,3). Maternal mortality ratio in
low- to middle-income countries is 14 times higher than in high-income
countries. This is partially due to lack of antenatal care, unmet needs for
Ac

family planning and education, as well as low rates of birth managed by


skilled attendants. While direct causes of maternal death such as
complications of hypertension, obstetric haemorrhage and sepsis remain the
largest cause of maternal death, cardiovascular disease emerges as an
important contributor to maternal mortality in both developing countries and
the developed world, hampering the achievement of the millennium
development goal, which aimed at reducing by three-quarters the maternal
mortality ratio until the end of 2015 (4). Maternal mortality rates rose markedly
from 2002 to 2006 in California. The California Pregnancy-Associated
Mortality Review retrospectively examined a case series of 64 cardiovascular
pregnancy-related deaths from 2002 through 2006. 864 died while pregnant
or within 1 year of pregnancy; 257 of the deaths were deemed pregnancy
related, and of these, 64 (25%) were attributed to cardiovascular disease (5).

2
Page 2 of 15
Cardiac disease is thus a leading cause of maternal death worldwide(6, 7).
The cardiac causes of death in pregnant and postpartum women vary
regarding their frequency and location in the world. There are few pathological
studies on maternal mortality related to cardiovascular diseases.

This study aims to present the cardiovascular causes of maternal sudden


death in United Kingdom and these patients’ characteristics. Both pathologists
and clinicians need to be aware of cardiac conditions leading to sudden

t
cardiac death, the effects of pregnancy and the risks of sudden death as

ip
maternal deaths due to cardiac diseases may be preventable if diagnosed
early.

cr
1 MATERIALS AND METHODS
1.1 Postmortem Examination

us
The Cardiac Risk in the Young (CRY) Cardiovascular pathology unit at St
George’s Medical School, London, acts as a specialist tertiary cardiac
pathology centre for sudden cardiac death (SCD) in the UK. All cases were
referred to our department because of a sudden cardiac death with no other

an
cause found at autopsy. Pathological analysis of all hearts was performed
with the consent of the coroner and the next of kin. The heart was examined
macroscopically and microscopically according to specific guidelines(8, 9).No
ethical approval was needed for this study.
M
1.1.1 Case Selection
We found 80 cases of maternal sudden death due to cardiac cause. We
included patients who died while pregnant and patients who died during the
d

postpartum period. Postpartum period was divided into three periods: initial or
acute period (the first 6–12 hours postpartum), subacute postpartum period
te

(up to six weeks after the end of pregnancy) and delayed postpartum period
(up to six months after the end of pregnancy) (10). We excluded direct
maternal deaths with amniotic fluid embolism (diagnosed from the presence of
p

fetal components in pulmonary vasculature), septic shock or directly due to


pre-eclampsia/eclampsia (diagnosed from the histological findings and clinical
ce

history) from this study. One limitation of the study is the absence of
ischaemic cardiac deaths which may reflect a referral bias to our centre.
Toxicology results were negative in all patients.
Ac

1.1.2 Data and Statistical Analysis


The patient’s age, circumstances of death and past medical history were
obtained from the referring pathologist/coroner. Patients were divided into two
age groups; one group under 35 years old and a second group 35 year old
and over. Obesity was defined according to WHO standards as BMI≥30 kg/m2
and above. Data are presented as mean±standard deviation. P values were
calculated using the student t test for continuous variables and the χ2 test for
independence or Fisher’s Exact test for categorical data. All tests were 2-
sided, and a significance value of P<0.05 was used. SPSS Statistics version
23 was used.

3
Page 3 of 15
2 RESULTS
2.1 Patients’ characteristics
A total 80 cases of maternal sudden cardiac death were identified from which
50% were during pregnancy and 50% postpartum (15% died in the initial or
acute period, 32.5% died in the subacute postpartum period and 2.5% died in
the delayed postpartum period). The mean age was 30±7 years with a range
from 16 to 43 years. 30% were 35 years old or older (Table 1).

t
ip
Data for BMI were available in 49 out of 80 cases (61.25% of the cohort) and
the mean BMI was 29.71±10 kg/m2 (range 18 to 70). Of these 49 cases,
42.86% were obese (BMI ≥ 30; n=21) and 16.33% were overweight (BMI ≥

cr
25, < 30; n=8).

2.2 Family History

us
A family history of premature sudden death (< 60 years) was documented in 6
out of the 80 cases with 4 reporting sudden death in <35 years.

2.3 Circumstances of death

an
The circumstances of death were mainly at rest (71.30%, n=57) followed by in
sleep (12.50%, n=10), during or immediately after physical/ emotional
exercise (5%, n=4), and unknown in 9 (11.30%). All the patients who died in
sleep were under 35 years old.
M
2.4 Symptoms prior to death
One or more cardiac symptoms immediately prior to death were reported in
30 out of 80 cases (37.50%), which were chest pain, shortness of breath,
d

syncope/collapse, dizziness and palpitations.


te

Cause of death (Table 2)

The main cause of death was sudden cardiac death with a morphologically
p

normal heart in 43 out of 80 cases (53.75%) following by cardiomyopathies in


ce

11 patients (13.80%) (7 dilated cardiomyopathy (Fig. 1), 2 obesity


Ac

cardiomyopathy, 1 arrhythmogenic right ventricular cardiomyopathy (ARVC),

1 Hypertrophic Cardiomyopathy (HCM)). Less common causes were 4 cases

of dissection of aorta (Fig. 2), 3 coronary artery dissection , 2 congenital heart

disease, 3 valvular diseases (2 floppy mitral valve and 1 mitral stenosis) and

14 miscellaneous causes (3 hypertension, 3 left ventricle hypertrophy one

with fibrosis, 1 thyrotoxic crisis during surgery for thyroid removal, 1 idiopathic

myocardial fibrosis, 1 Libman-Sacks endocarditis with SLE and

4
Page 4 of 15
atherosclerosis, 4 heart block, 1 myotonic dystrophy with dilated

cardiomyopathy.

Patients who died with a morphological normal heart were mainly under 35

years old while patients who died due to cardiomyopathy did not have

t
significant difference between the two age groups.

ip
Discussion

cr
We report 80 cases who died during pregnancy or postpartum. The mean age

was 30 years and 30% were 35 years old or older. It has been reported in the

us
literature, that women older than 35 years old have a high risk of sudden

an
death(11). Similarly, this study shows that sudden cardiac death is more likely

to occur to old females rather than to the young ones. Also, 59.18% were
M
obese or overweight (BMI ≥ 25 kg/m2). This finding suggests that BMI is a risk

factor of maternal sudden cardiac death and it should be taken in account in


d

daily clinical practice. BMI, as a risk factor, is not associated with the age of
te

the woman. High percentage of obese females who suffered a sudden cardiac

maternal death has also previously been reported in other studies(12, 13).
p

According to the eighth report of the confidential enquiries into maternal


ce

deaths in the United Kingdom, maternal death autopsies are often complex

and challenging and require more expertise than the average autopsy (14). To
Ac

our knowledge, this is the largest autopsy series of maternal cardiac deaths

and is based on the findings of a specialised cardiac pathology centre.

The vast majority of our cases had a morphologically normal heart indicating

sudden arrhythmic death syndrome (SADS) with the likelihood of death being

precipitated by an electrical disturbance as in the channelopathies (15).

Screening of families is essential since these channelopathies have been

5
Page 5 of 15
identified in up to 50% of families (16). Pregnancy may precititate the first

presentation of cardiac arrhythmia and point to an underlying channelopathy

or the patient may already be aware of such a diagnosis in herself or other

family members. A history of sudden young death in the family is very

t
important. The risk of pregnancy must be considered and obstetricians made

ip
aware of the family history or previous diagnosis. 6 of our SADS cases had a

cr
previous family history of sudden young death with 4 being under 35 years

old. In the pregnancy or postpartum period, arrhythmias may be a recurrence

us
of a previously diagnosed arrhythmia but in most cases there is no previous

an
history of arrhythmias or a diagnosis of a channelopathy (17).

Only few cases of SADS have been identified in previous maternal death
M
surveys. In the UK, the confidential enquiries started reported for the first time

this condition for the triennium 2000-2002. Maternal deaths with SADS may
d

not be so rare since the latest report counted 10 maternal SADS for 2006-
te

2008, making it an important cause (14). In view from the common occurrence

of postpartum deaths with SADS as shown in this study and the previous
p

confidential enquiries, there are cases left unascertained or unreported as a


ce

maternal death because of the remoteness from the pregnancy. It is important

to raise awareness of SADS in obstetric practice and examine the impact of


Ac

pregnancy on pathophysiological mechanisms of SADS. Brugada syndrome,

one of the channelopathies, is common in women, representing 42% of

patients in a recent database with higher risk of arrhythmic events in some

females (18).

This paper confirms the contribution of cardiomyopathies to maternal death. In

addition to the importance of dilated cardiomyopathy, particularly peripartum

6
Page 6 of 15
cardiomyopathy as shown in both UK(14) and US

data(19),Netherlands(20,21). Our study highlights obesity and hypertrophic

cardiomyopathy and arrhythmogenic cardiomyopathy. Only a few cases of

pregnancies with ARVC have been reported (22-24). It is noted in general

t
studies hat SADS is often underestimated (25,26) and cardiomyopathies over-

ip
diagnosed (27). Hypertensive disease, rheumatic heart disease and

cr
cardiomyopathies are major health problems in pregnancy, worldwide.

Undetected or untreated congenital heart defects, undiagnosed pulmonary

us
hypertension, uncontrolled heart failure and complications of sickle cell

an
disease are important challenges. Six factors in a UK study were

independently associated with maternal death: inadequate use of antenatal


M
care, substance misuse, medical comorbidities previous pregnancy problems,

hypertensive disorders of pregnancy and Indian ethnicity (28). In a USA study,


d

42 deaths were caused by cardiomyopathy, and the pregnancy-related


te

mortality rate from cardiomyopathy was 1.54 per 100,000 births. Women with

cardiovascular disease were more likely than women who died from non-
p

cardiovascular causes to be African-American and more likely to use illicit


ce

substances 37% were obese and 20% had a concomitant diagnosis of

hypertension or preeclampsia during pregnancy. (5) This study also


Ac

emphasises death in pregnancy and following delivery with pulmonary

hypertension. Pregnancy with congenital heart disease and pulmonary

hypertension is associated with a markedly increased risk of adverse

cardiovascular events and death for delivery and in the post-partum period

(29-32). Pulmonary arterial hypertension (PAH), including Eisenmenger

syndrome, has a risk of mortality in pregnancy of 10-40% (33).

7
Page 7 of 15
An association between pregnancy and aortic dissection is well established.

Because of increasing cardiovascular stress during pregnancy, the risk of

aortic dissection or rupture of an aneurysm increases with gestational age. In

this situation dissection and rupture of the aorta carry a high risk of maternal

t
mortality (34). All of these are thoracic dissections which can be also familial

ip
(35). Dissection of coronary arteries also occurs during pregnancy and the

cr
prognosis is poor with a high mortality of 38% (36,37). Increased estrogen

concentrations during pregnancy are known to cause increased fragmentation

us
of reticulin fibers, reduce acid mucopolysaccharides and loss of normal

an
corrugation of elastic fibers which may explain the higher risk of dissection in

these vessels (38). In Netherlands vascular dissection was the leading cause
M
of maternal death (39).

Heart block was reported in 4 cases and can be a challenge in pregnancy


d

(40).
te

In conclusion, significant risk factors of maternal death are age, BMI and

family history. These risk factors should be taken into account in clinical
p

obstetric practice. Patients with these risk factors need cardiac screening by a
ce

cardiologist with expertise in electrophysiology. SADS as a cause of maternal

death has only recently been recognised and we need to make the obstetric
Ac

community aware of these entities and the increased risks during pregnancy

and afterwards.

This study highlight that maternal cardiac death are due mainly to SADS in

UK. In these cases, a detailed past family history of sudden death or cardiac

arrhythmias is essential and screening of other family members is indicated to

avoid further deaths since these entities are commonly inherited.

8
Page 8 of 15
One limitation of the study is the absence of ischaemic cardiac deaths which

may reflect a referral bias to our centre.

Synopsis: Sudden Arrhythmic Death Syndrome is a leading cause of

maternal sudden cardiac death in United Kingdom.

t
ip
cr
Author Contribution

us
Both authors contributed to the design of the work, the acquisition, analysis,

and interpretation of data for the work, drafting the work, revising it critically

an
for important intellectual content, final approval of the version to be published

and agreement to be accountable for all aspects of the work in ensuring that
M
questions related to the accuracy or integrity of any part of the work are

appropriately investigated and resolved. Both authors are guarantors of the


d

paper. We assure that there is no one else who fulfils the criteria but has not
te

been included as an author.


p

The manuscript is an honest, accurate, and transparent account of the study


ce

being reported; that no important aspects of the study have been omitted; and

that any discrepancies from the study as planned have been explained.
Ac

Competing interests

All authors have completed the ICMJE uniform disclosure form at

www.icmje.org/coi_disclosure.pdf and declare: no support from any

organisation for the submitted work; no financial relationships with any

organisations that might have an interest in the submitted work in the previous

three years; no other relationships or activities that could appear to have

influenced the submitted work.

9
Page 9 of 15
Funding

Cardiac Risk in the Young (CRY)

Ethical Approval

t
No ethical approval was needed

ip
cr
Licence for Publication

The Corresponding Author has the right to grant on behalf of all authors and

us
does grant on behalf of all authors, a worldwide licence to the Publishers and

an
its licensees in perpetuity, in all forms, formats and media (whether known

now or created in the future), to i) publish, reproduce, distribute, display and


M
store the Contribution, ii) translate the Contribution into other languages,

create adaptations, reprints, include within collections and create summaries,


d

extracts and/or, abstracts of the Contribution, iii) create any other derivative
te

work(s) based on the Contribution, iv) to exploit all subsidiary rights in the

Contribution, v) the inclusion of electronic links from the Contribution to third


p

party material where-ever it may be located; and, vi) licence any third party to
ce

do any or all of the above


Ac

References
1. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C,
Heuton KR, et al. Global, regional, and national levels and causes of maternal
mortality during 1990-2013: a systematic analysis for the Global Burden of Disease
Study 2013. Lancet. 2014;384(9947):980-1004.
2. Shah IH, Say L. Maternal mortality and maternity care from 1990 to 2005:
uneven but important gains. Reprod Health Matters. 2007;15(30):17-27.

10
Page 10 of 15
3. Koonin LM, MacKay AP, Berg CJ, Atrash HK, Smith JC. Pregnancy-related
mortality surveillance--United States, 1987-1990. MMWR CDC Surveill Summ.
1997;46(4):17-36.
4. Mocumbi AO, Sliwa K, Soma-Pillay P. Medical disease as a cause of maternal
mortality: the pre-imminence of cardiovascular pathology. Cardiovascular journal of
Africa. 2016;27(2):84-8.
5. Hameed AB, Lawton ES, McCain CL, Morton CH, Mitchell C, Main EK, et al.

t
Pregnancy-related cardiovascular deaths in California: beyond peripartum

ip
cardiomyopathy. American journal of obstetrics and gynecology. 2015;213(3):379
e1-10.
6. Haththotuwa HR, Attygalle D, Jayatilleka AC, Karunaratna V, Thorne SA.

cr
Maternal mortality due to cardiac disease in Sri Lanka. Int J Gynaecol Obstet.
2009;104(3):194-8.
7. Engin-Üstün Y, Çelen Ş, Özcan A, Sanisoğlu S, Karaahmetoğlu S, Gül R, et al.

us
Maternal mortality from cardiac disease in Turkey: a population-based study. J
Matern Fetal Neonatal Med. 2012;25(11):2451-3.
8. Basso C, Burke M, Fornes P, Gallagher PJ, de Gouveia RH, Sheppard M, et al.

an
Guidelines for autopsy investigation of sudden cardiac death. Virchows Arch.
2008;452(1):11-8.
9. Sheppard MN. Approach to the cardiac autopsy. J Clin Pathol.
2012;65(6):484-95.
M
10. Romano M, Cacciatore A, Giordano R, La Rosa B. Postpartum period: three
distinct but continuous phases. J Prenat Med. 2010;4(2):22-5.
11. Laopaiboon M, Lumbiganon P, Intarut N, Mori R, Ganchimeg T, Vogel JP, et al.
Advanced maternal age and pregnancy outcomes: a multicountry assessment. BJOG.
d

2014;121 Suppl 1:49-56.


12. Hameed AB, Lawton ES, McCain CL, Morton CH, Mitchell C, Main EK, et al.
te

Pregnancy-related cardiovascular deaths in California: beyond peripartum


cardiomyopathy. Am J Obstet Gynecol. 2015.
p

13. Lamminpää R, Vehviläinen-Julkunen K, Gissler M, Selander T, Heinonen S.


Pregnancy outcomes of overweight and obese women aged 35 years or older - A
ce

registry-based study in Finland. Obes Res Clin Pract. 2015.


14. Wilkinson H, Advisers TaM. Saving mothers' lives. Reviewing maternal deaths
to make motherhood safer: 2006-2008. BJOG. 2011;118(11):1402-3; discussion 3-4.
15. Webster G, Berul CI. An update on channelopathies: from mechanisms to
Ac

management. Circulation. 2013;127(1):126-40.


16. Campuzano O, Allegue C, Partemi S, Iglesias A, Oliva A, Brugada R. Negative
autopsy and sudden cardiac death. Int J Legal Med. 2014;128(4):599-606.
17. Adamson DL, Nelson-Piercy C. Managing palpitations and arrhythmias during
pregnancy. Heart. 2007;93(12):1630-6.
18. Sieira J, Conte G, Ciconte G, de Asmundis C, Chierchia G-B, Baltogiannis G, et
al. Clinical characterisation and long-term prognosis of women with Brugada
syndrome. Heart. 2016.
19. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM.
Pregnancy-related mortality in the United States, 2006-2010. Obstet Gynecol.
2015;125(1):5-12.

11
Page 11 of 15
20. Schutte JM, Steegers EA, Schuitemaker NW, Santema JG, de Boer K, Pel M, et
al. Rise in maternal mortality in the Netherlands. BJOG. 2010;117(4):399-406.
21. Gunderson EP, Croen LA, Chiang V, Yoshida CK, Walton D, Go AS.
Epidemiology of peripartum cardiomyopathy: incidence, predictors, and outcomes.
Obstet Gynecol. 2011;118(3):583-91.
22. Agir A, Bozyel S, Celikyurt U, Argan O, Yilmaz I, Karauzum K, et al.
Arrhythmogenic right ventricular cardiomyopathy in pregnancy. International heart

t
journal. 2014;55(4):372-6.

ip
23. Iriyama T, Kamei Y, Kozuma S, Taketani Y. Management of patient with
arrhythmogenic right ventricular cardiomyopathy during pregnancy. J Obstet
Gynaecol Res. 2013;39(1):390-4.

cr
24. Lee LC, Bathgate SL, Macri CJ. Arrhythmogenic right ventricular dysplasia in
pregnancy: a case report. J Reprod Med. 2006;51(9):725-8.
25. Behr ER, Casey A, Sheppard M, Wright M, Bowker TJ, Davies MJ, et al. Sudden

us
arrhythmic death syndrome: a national survey of sudden unexplained cardiac death.
Heart. 2007;93(5):601-5.
26. Koplan BA, Stevenson WG. Sudden arrhythmic death syndrome. Heart.

an
2007;93(5):547-8.
27. de Noronha SV, Behr ER, Papadakis M, Ohta-Ogo K, Banya W, Wells J, et al.
The importance of specialist cardiac histopathological examination in the
investigation of young sudden cardiac deaths. Europace. 2014;16(6):899-907.
M
28. Nair M, Kurinczuk JJ, Brocklehurst P, Sellers S, Lewis G, Knight M. Factors
associated with maternal death from direct pregnancy complications: a UK national
case-control study. BJOG : an international journal of obstetrics and gynaecology.
2015;122(5):653-62.
d

29. Opotowsky AR, Siddiqi OK, D'Souza B, Webb GD, Fernandes SM, Landzberg
MJ. Maternal cardiovascular events during childbirth among women with congenital
te

heart disease. Heart. 2012;98(2):145-51.


30. Bowater SE, Thorne SA. Management of pregnancy in women with acquired
p

and congenital heart disease. Postgrad Med J. 2010;86(1012):100-5.


31. Curry R, Swan L, Steer PJ. Cardiac disease in pregnancy. Current opinion in
ce

obstetrics & gynecology. 2009;21(6):508-13.


32. Rosengarten D, Kramer MR. [Pregnancy in pulmonary arterial hypertension
patients]. Harefuah. 2013;152(9):547-51, 63, 62.
33. Krexi D, Sheppard MN. Pulmonary hypertensive vascular changes in lungs of
Ac

patients with sudden unexpected death. Emphasis on congenital heart disease,


Eisenmenger syndrome, postoperative deaths and death during pregnancy and
postpartum. Journal of clinical pathology. 2015;68(1):18-21.
34. Immer FF, Bansi AG, Immer-Bansi AS, McDougall J, Zehr KJ, Schaff HV, et al.
Aortic dissection in pregnancy: analysis of risk factors and outcome. Ann Thorac
Surg. 2003;76(1):309-14.
35. Wanga S, Silversides C, Dore A, de Waard V, Mulder B. Pregnancy and
Thoracic Aortic Disease: Managing the Risks. The Canadian journal of cardiology.
2016;32(1):78-85.
36. Koul AK, Hollander G, Moskovits N, Frankel R, Herrera L, Shani J. Coronary
artery dissection during pregnancy and the postpartum period: two case reports and
review of literature. Catheter Cardiovasc Interv. 2001;52(1):88-94.

12
Page 12 of 15
37. Herbst J, Winskog C, Byard RW. Cardiovascular conditions and the evaluation
of the heart in pregnancy-associated autopsies. Journal of forensic sciences.
2010;55(6):1528-33.
38. Manalo-Estrella P, Barker AE. Histopathologic findings in human aortic media
associated with pregnancy. Arch Pathol. 1967;83(4):336-41.
39. Schutte JM, de Jonge L, Schuitemaker NW, Santema JG, Steegers EA, van
Roosmalen J. Indirect maternal mortality increases in the Netherlands. Acta

t
obstetricia et gynecologica Scandinavica. 2010;89(6):762-8.

ip
40. Sundararaman L, Hochman Cohn J, Ranasinghe JS. Complete heart block in
pregnancy: case report, analysis, and review of anesthetic management. Journal of
clinical anesthesia. 2016;33:58-61.

cr
us
Fig. 1 Dilated cardiomyopathy with thin wall and hypertrabeculation

an
Fig. 2 Aortic dissection M
Table 1 Characteristics Stratified by Age

16-34 y 35-43 y Total P Value


d

N 56 24 80
te

Age, mean±SD, median 27.21±4.94 37.67±2.26 30±7

BMI, mean±SD, N 27.70±7.78, 34 34.28±12.99, 15 29.71±10, 49 0.084


p

Symptoms prior to death, N 22 (39.30%) 8 (33.30%) 30 (37.50%) 0.614

(%)
ce

Morphological normal heart, 35 (62.50%) 8 (33.30%) 43 (53.75%) 0.016*

N (%)
Ac

Cardiomyopathy, N (%) 7 (12.50%) 4 (16.70%) 11 (13.80%) 0.620

Other cause of death, N (%) 14 (25%) 12 (50.00%) 23 (32.50%) 0.029*

Pregnant, N (%) 32 (57.10%) 8 (33.30%) 40 (50%) 0.051

Postpartum, N (%) 24 (42.90%) 16 (66.70%) 40 (50%) 0.051

Death in sleep, N (%) 10 (17.90%) 0 (0%) 10 (12.50%) 0.028*

Death at rest, N (%) 42 (75%) 15 (62.50%) 57 (71.3%) 0.258

Death with exersion/ stress, 2 (3.60%) 2 (8.30%) 4 (5.00%) 0.579

N (%)

13
Page 13 of 15
Unknown, N (%) 2 (3.60%) 7 (29.20%) 9 (11.30%) 0.002*

Table 2 Causes of Death

Cause of Death Total % cohort

Morphological Normal Heart 43 53.75

t
ip
Cardiomyopathy 11 13.80

cr
Dissection of Aorta or its 7 8.75

branches

us
Congenital Heart Disease 2 2.50

Valvular Diseases 3 3.75

Floppy Mitral Valve

Mitral Stenosis
2

1 an 2.50

1.25
M
Miscellaneous Causes 14 17.50
d
p te
ce
Ac

14
Page 14 of 15
Filename: 9810.doc
Directory: C:\FMS\MNT_ELSEVIER_JOURNAL_EURO_9810_1
Template: C:\teesels\Normal.dot
Title:
Subject:
Author: home
Keywords:

t
Comments:

ip
Creation Date: 3/7/2017 4:04 PM
Change Number: 12
Last Saved On: 3/7/2017 4:33 PM

cr
Last Saved By: fs
Total Editing Time: 5 Minutes

us
Last Printed On: 3/7/2017 4:33 PM
As of Last Complete Printing
Number of Pages: 14
Number of Words: 27,448 (approx.)

an
Number of Characters: 156,459 (approx.)
M
d
p te
ce
Ac

Page 15 of 15