European Journal of Heart Failure (2016) 18, 534–536 EDITORIAL COMMENT

doi:10.1002/ejhf.522

Risk assessment for pregnancy with cardiac

disease—a global perspective
Karen Sliwa1,2* and John Anthony3
1 HatterInstitute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, SA MRC Cape Heart Centre, University of Cape Town, South Africa;
2 Soweto Cardiovascular Research Unit, University of the Witwatersrand, Johannesburg, South Africa; and 3 Division of Obstetrics and Gynaecology, Groote Schuur Hospital,
University of Cape Town, South Africa

This article refers to ‘Global cardiac risk assessment in The mWHO classification showed only a moderate performance

.........................................................................................................
the Registry Of Pregnancy And Cardiac disease: results in predicting risk between women with or without cardiac events
of a registry from the European Society of Cardiology’, [c-statistic 0.711, 95% confidence interval (CI) 0.686–0.735] with a
by I.M. van Hagen, et al., published in this issue on pages better performance in advanced countries compared with emerg-
523–533. ing countries. Novel findings were that pre-pregnancy signs of heart
failure and atrial fibrillation added prognostic value in advanced
Cardiac disease is emerging as the most important indirect cause countries. However, follow-up was only available for all patients up
if maternal death globally.1 Cardiac conditions can be pre-existing to 1 week after delivery, probably missing a number of events such
(e.g. rheumatic or congenital heart disease) and unmasked by as additional heart failure, prosthetic valve complications, or sud-
increased volume load in pregnancy, or can be caused by preg- den death.2 The authors provided a very useful colour-coded risk
nancy [e.g. hypertensive disorders or peripartum cardiomyopathy chart, which determines <35%, 35–65%, and more than 65% risk
(PPCM)].2,3 Physicians are therefore increasingly faced with provid- in emerging and advanced countries according to pre-pregnancy
ing adequate counselling on pregnancy risk to women wishing to mWHO class. Is this chart based on the mWHO comprehensive
conceive who are known to have cardiac disease (e.g. operated enough? Probably not.
congenital heart disease or previous valve replacement because Mortality data contextualize the risk of cardiac disease in preg-
of rheumatic heart disease), or present in the advanced stage of nancy with case fatality rates approaching 1 in 200.5 This has refer-
pregnancy (>20 weeks) having heart failure because of pre-existing ence to other obstetric complications that are viewed as high-risk;
or newly acquired cardiac disease. The strength of epidemiological for example pre-eclampsia has a cited case fatality rate of 1 in 1500
data used as a basis for counselling is a function of sample size and, and eclampsia leads to mortality in 1 in 50 cases.6,7 The maternal
although cardiac disease may be globally prevalent, single centres mortality ratio in low-to-middle income countries (LIMCs) is 14
have too few patients to create meaningful datasets for analysis. times higher than in high-income countries (HICs).8 A number of
Internationally constructed databases provide a bigger dataset from deficiencies, including lack of ante-natal care, late booking, lack of
which inferences can be drawn. appropriate referral systems to higher level of care, no family plan-
Iris van Hagen and colleagues4 validated the modified World ning, overall poor education, and low rates of birth managed by
Health Organization (mWHO) risk classification in advanced and skilled health-care attendants contribute to the high maternal death
emerging countries and identified additional risk factors for car- rates in LIMCs. Direct causes of maternal death such as obstetric
diac events during pregnancy using data from the Registry of Preg- haemorrhage and sepsis, as well as complications of hypertensive
nancy and Cardiac Disease (ROPAC), which includes more than disorders of pregnancy remain the biggest numerical contributors.
2500 pregnant women. The spectrum of cardiac disease differed These direct causes can also occur in women with cardiac dis-
in advanced vs. emerging countries with congenital heart disease ease; for example, obstetric haemorrhage can complicate delivery
being the most prevalent diagnosis in advanced countries, and in women with a prosthetic heart valve needing anti-coagulation.
valvular heart disease and cardiomyopathies being the most com- In LMICs, searches for heart disease in pregnant women is not
mon diagnoses in emerging countries. There was a substantial dif- performed routinely, and peripartum cardiomyopathy, Chagas dis-
ference in cardiac events between regions, occurring in 12.8% of ease, human immunodeficiency virus (HIV) cardiomyopathy, and
patients in advanced countries vs. 36.3% in emerging countries. endomyocardial fibrosis present specific challenges because of their

The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology.
DOI: 10.1002/ejhf.501
*Corresponding author: Hatter Institute for Cardiovascular Research in Africa, Cape Heart Centre, 4th Floor Chris Barnard Building, Faculty of Health Sciences, University of
Cape Town, Private Bag X3, Observatory, 7935 Cape Town, South Africa. Tel: +27 21 406 6457; E-mail: Karen.Sliwa-Hahnle@uct.ac.za

© 2016 The Authors

European Journal of Heart Failure © 2016 European Society of Cardiology
Editorial Comment 535

Maternal Health Factors

Late presentation ( > 20 weeks)
Pre-existing heart failure
Atrial Fibrillation
Anaemia

Conditions listed at the Modified

WHO stage I-IV

Conditions not listed as:

Cardiac sarcoidosis, constrictive Health System Factors
pericarditis, Un-skilled health care workers
HIV Cardiomyopathy Lack of tools to make early
Chagas’ cardiomyopathy and others diagnosis
Inappropriate referral algorithm
Long distance to appropriate
care
Maternal Socioeconomic Factors:
Age < 18 or Age > 35
Poor maternal education
Low household income
Long distance to appropriate care

Figure 1 Factors contributing to increased maternal and fetal risk in pregnant women with heart disease.

poor prognosis and high prevalence in some geographical areas.9 of congenital disease, this is likely to reflect the occurrence of
................................................................................................

Anaemia caused by a number of conditions such as poor nutrition, surgical intervention, whereas in emerging countries both medical
helminthic infections, and malaria are common among pregnant and surgical intervention related to congenital and valvular heart
women in LMICs, contributing to heart failure in women with disease is likely to play a role. The data serve to underscore the
cardiac disease. In the global prospective registry of rheumatic value of treatment before pregnancy: ‘The mWHO, even if factors
heart disease (REMEDY), which enrolled 3343 patients, 1825 were such as AF [atrial fibrillation] and pre-existing heart failure are
women of child-bearing age (12–51 years) and only 65 (3.6%) were included, still has a number of deficiencies as a comprehensive
using contraception, reflecting the poor provision of family plan- risk prediction score, even if factors such as atrial fibrillation
ning and pre-pregnancy advice for a condition that occurs in many and pre-existing heart failure are included. Firstly, it includes only
regions of the world.10 risks for the women with cardiac disease and fails to highlight
Data from the current publication4 also outline the general risk the effects on the fetus in advanced cardiac disease (e.g. which
of adverse events taking place during pregnancy; it is unsurprising can be intrauterine death, low birth weight, and preterm birth
but useful to know that mWHO 4 category patients have a one with long-term consequences). Many conditions common in LMICs
in two risk of such an event and that the percentage of patients and elsewhere are also not included in the mWHO, including for
falling into this category is far greater in emerging countries than example: Chagas’ disease, HIV CMO, cardiac sarcoidosis amongst
in developed nations. It is also notable that valvular heart disease others.’
is more likely to fall into mWHO category 3 and category 4 than Other cofactors increasing the risk of morbidity such as low or
other cardiac diseases. high maternal age, anaemia, poor nutrition, and being underweight
The data presented bear further consideration insofar as the or severely overweight are also not included. Most importantly
risk of adverse events between mWHO category 1 and category 2 socioeconomic factors such as low education of the mother and
show a similar incidence, possibly indicating that patients previously unskilled health-care workers, lack of appropriate tools to make an
assigned to low-risk categories merit multidisciplinary assessment early diagnosis, or detection of heart failure, and long distances to
both at the beginning of pregnancy and again immediately before tertiary care need to be part of the overall risk assessment.
delivery. Figure 1 highlights the factors that are likely to contribute to
The analysis of parity also provokes speculation because increas- increased maternal and fetal risk in pregnant women with cardiac
ingly severe disease is associated with a falling prevalence of nul- disease which could be used in conjunction with the risk chart for
liparity despite little difference in maternal age. This may point to cardiac events by Hagen et al.4 Specific guidelines on management
the cumulative effects of successive pregnancies on cardiac function of women with un-operated or operated rheumatic heart disease
and merits further investigation. in LMICs were also recently published.11
The influence of cardiac intervention in decreasing the risk of In summary, risk prediction for pregnant women with heart
adverse events is also notable in both emerging and advanced disease should consider the unique profile of cardiovascular dis-
country datasets. In advanced countries, with a higher proportion ease in LMICs and the contribution of a number of risk factors.

© 2016 The Authors

European Journal of Heart Failure © 2016 European Society of Cardiology
536 Editorial Comment

Counselling individual patients is an integral component of med- Nolte S, Norheim OF, Nyakarahuka L, Oh IH, Ohkubo T, Olusanya BO, Omer

............................................................................................................................
SB, Opio JN, Orisakwe OE, Pandian JD, Papachristou C, Park JH, Caicedo AJ,
ical care in which an estimate of risk is recognized to be this
Patten SB, Paul VK, Pavlin BI, Pearce N, Pereira DM, Pesudovs K, Petzold M,
very composite of disease-specific risk, risk arising from individual Poenaru D, Polanczyk GV, Polinder S, Pope D, Pourmalek F, Qato D, Quistberg
variability related to biological susceptibility, and co-morbid condi- DA, Rafay A, Rahimi K, Rahimi-Movaghar V, ur Rahman S, Raju M, Rana SM, Refaat
A, Ronfani L, Roy N, Pimienta TG, Sahraian MA, Salomon JA, Sampson U, Santos
tions combined with environmental circumstances, often induced
IS, Sawhney M, Sayinzoga F, Schneider IJ, Schumacher A, Schwebel DC, Seedat
by lack of resources and expertise. All these elements are difficult S, Sepanlou SG, Servan-Mori EE, Shakh-Nazarova M, Sheikhbahaei S, Shibuya K,
to integrate into a single risk estimate to which individual patients Shin HH, Shiue I, Sigfusdottir ID, Silberberg DH, Silva AP, Singh JA, Skirbekk V,
Sliwa K, Soshnikov SS, Sposato LA, Sreeramareddy CT, Stroumpoulis K, Sturua L,
can attach a particular value.
Sykes BL, Tabb KM, Talongwa RT, Tan F, Teixeira CM, Tenkorang EY, Terkawi AS,
The current dataset extends our statistical knowledge of risk and Thorne-Lyman AL, Tirschwell DL, Towbin JA, Tran BX, Tsilimbaris M, Uchendu
if health system issues could be incorporated in risk prediction it US, Ukwaja KN, Undurraga EA, Uzun SB, Vallely AJ, van Gool CH, Vasankari TJ,
Vavilala MS, Venketasubramanian N, Villalpando S, Violante FS, Vlassov VV, Vos
may improve our ability to counsel patients and avoid a substantial
T, Waller S, Wang H, Wang L, Wang X, Wang Y, Weichenthal S, Weiderpass
portion of maternal morbidity and mortality. E, Weintraub RG, Westerman R, Wilkinson JD, Woldeyohannes SM, Wong JQ,
Conflict of interest: None to declare. Wordofa MA, Xu G, Yang YC, Yano Y, Yentur GK, Yip P, Yonemoto N, Yoon SJ,
Younis MZ, Yu C, Jin KY, El Sayed Zaki M, Zhao Y, Zheng Y, Zhou M, Zhu J, Zou
XN, Lopez AD, Naghavi M, Murray CJ, Lozano R. Global, regional, and national
levels and causes of maternal mortality during 1990–2013: a systematic analysis
References for the Global Burden of Disease Study 2013. Lancet 2014;384:980–1004.
1. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, 2. Sliwa K, Libhaber E, Elliott C, Momberg Z, Osman A, Zuhlke L, Lachmann
Heuton KR, Gonzalez-Medina D, Barber R, Huynh C, Dicker D, Templin T, T, Nicholson L, Thienemann F, Roos-Hesselink J, Anthony J. Spectrum of
Wolock TM, Ozgoren AA, Abd-Allah F, Abera SF, Abubakar I, Achoki T, cardiac disease in maternity in a low-resource cohort in South Africa. Heart
Adelekan A, Ademi Z, Adou AK, Adsuar JC, Agardh EE, Akena D, Alasfoor 2014;100:1967–1974.
D, Alemu ZA, Alfonso-Cristancho R, Alhabib S, Ali R, Al Kahbouri MJ, Alla F, 3. Naidoo P, Desai D, Moodley J. Maternal deaths due to pre-existing cardiac
Allen PJ, AlMazroa MA, Alsharif U, Alvarez E, Alvis-Guzman N, Amankwaa AA, disease. Cardiovasc J Afr 2002;13:17–19.
Amare AT, Amini H, Ammar W, Antonio CA, Anwari P, Arnlov J, Arsenijevic VS, 4. van Hagen I, Boersma E, Johnson M, Thorne S, Parsonage W, Subias P,
Artaman A, Asad MM, Asghar RJ, Assadi R, Atkins LS, Badawi A, Balakrishnan K, Lesniak-Sobelga A, Iryuga O, Sorour K, Taha N, Maggioni AP, Hall R,
Basu A, Basu S, Beardsley J, Bedi N, Bekele T, Bell ML, Bernabe E, Beyene TJ, Roos-Hesselink J. Global cardiac risk assessment in the Registry Of Pregnancy
Bhutta Z, Bin Abdulhak A, Blore JD, Basara BB, Bose D, Breitborde N, Cardenas And Cardiac disease: results of a registry from the European Society of
R, Castaneda-Orjuela CA, Castro RE, Catala-Lopez F, Cavlin A, Chang JC, Che Cardiology. Eur J Heart Fail 2016;18:523–533.
X, Christophi CA, Chugh SS, Cirillo M, Colquhoun SM, Cooper LT, Cooper C, 5. MacKay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia
da Costa Leite I, Dandona L, Dandona R, Davis A, Dayama A, Degenhardt L, and eclampsia. Obstetr Gynecol 2001;97:533–538.
De Leo D, del Pozo-Cruz B, Deribe K, Dessalegn M, deVeber GA, Dharmaratne 6. Douglas KA, Redman C. Eclampsia in the United Kingdom. BMJ
SD, Dilmen U, Ding EL, Dorrington RE, Driscoll TR, Ermakov SP, Esteghamati A, 1994;309:1395–1400.
Faraon EJ, Farzadfar F, Felicio MM, Fereshtehnejad SM, de Lima GM, Forouzanfar 7. Knight M. Eclampsia in the United Kingdom 2005. BJOG 2007;114:
MH, Franca EB, Gaffikin L, Gambashidze K, Gankpe FG, Garcia AC, Geleijnse JM, 1072–1078.
Gibney KB, Giroud M, Glaser EL, Goginashvili K, Gona P, Gonzalez-Castell D, 8. United Nations. Millennium Development Goals Report 2013. United Nations, New
Goto A, Gouda HN, Gugnani HC, Gupta R, Gupta R, Hafezi-Nejad N, Hamadeh York; 2013.
RR, Hammami M, Hankey GJ, Harb HL, Havmoeller R, Hay SI, Pi IB, Hoek HW, 9. Mocumbi AO, Sliwa K, Soma-Pillay P. Medical disease as a cause for maternal
Hosgood HD, Hoy DG, Husseini A, Idrisov BT, Innos K, Inoue M, Jacobsen KH, mortality: the pre-imminence of cardiovascular pathology. Cardiovasc J Afr 2016;
Jahangir E, Jee SH, Jensen PN, Jha V, Jiang G, Jonas JB, Juel K, Kabagambe EK, in press.
Kan H, Karam NE, Karch A, Karema CK, Kaul A, Kawakami N, Kazanjan K, 10. Zühlke L, Engel ME, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, Mauff
Kazi DS, Kemp AH, Kengne AP, Kereselidze M, Khader YS, Khalifa SE, Khan EA, K, Islam S, Joachim A, Daniels R, Francis V, Ogendo S, Gitura B, Mondo C,
Khang YH, Knibbs L, Kokubo Y, Kosen S, Defo BK, Kulkarni C, Kulkarni VS, Okello E, Lwabi P, Al-Kebsi MM, Hugo-Hamman C, Sheta SS, Haileamlak A,
Kumar GA, Kumar K, Kumar RB, Kwan G, Lai T, Lalloo R, Lam H, Lansingh Daniel W, Goshu DY, Abdissa SG, Desta AG, Shasho BA, Begna DM, ElSayed
VC, Larsson A, Lee JT, Leigh J, Leinsalu M, Leung R, Li X, Li Y, Li Y, Liang J, A, Ibrahim AS, Musuku J, Bode-Thomas F, Okeahialam BN, Ige O, Sutton C,
Liang X, Lim SS, Lin HH, Lipshultz SE, Liu S, Liu Y, Lloyd BK, London SJ, Lotufo Misra R, Abul Fadl A, Kennedy N, Damasceno A, Sani M, Ogah OS, Olunuga T,
PA, Ma J, Ma S, Machado VM, Mainoo NK, Majdan M, Mapoma CC, Marcenes Elhassan HH, Mocumbi AO, Adeoye AM, Mntla P, Ojji D, Mucumbitsi J, Teo K,
W, Marzan MB, Mason-Jones AJ, Mehndiratta MM, Mejia-Rodriguez F, Memish Yusuf S, Mayosi BM. Characteristics, complications, and gaps in evidence-based
ZA, Mendoza W, Miller TR, Mills EJ, Mokdad AH, Mola GL, Monasta L, de la interventions in rheumatic heart disease: the Global Rheumatic Heart Disease
Cruz Monis J, Hernandez JC, Moore AR, Moradi-Lakeh M, Mori R, Mueller UO, Registry (the REMEDY study). Eur Heart J. 2015;36:1115–1122a.
Mukaigawara M, Naheed A, Naidoo KS, Nand D, Nangia V, Nash D, Nejjari 11. Sliwa K, Johnson MR, Zilla P, Roos-Hesselink JW. Management of valvular disease
C, Nelson RG, Neupane SP, Newton CR, Ng M, Nieuwenhuijsen MJ, Nisar MI, in pregnancy: a global perspective. Eur Heart J. 2015;36:1078–1089.

© 2016 The Authors

European Journal of Heart Failure © 2016 European Society of Cardiology