Over the past 25 years, pregnancy-related mortality has doubled in the United States.1 Cardiovascular disease has emerged as a leading and increasing cause of maternal mortality in the United States and globally.2–5 Until recently, two of the most common causes of maternal mortality were hemorrhagic and embolic disease (pulmonary and amniotic fluid embolism).4 However, improvements in diagnosis and management of these conditions, especially hemorrhagic complications, have resulted in significant decreases in associated mortality. Despite this, maternal mortality has risen. Cardiovascular disease, therefore, remains a leading contributor to U.S. maternal mortality that needs to be addressed.1,4,5
The physiologic requirements of pregnancy challenge women with both known and undiagnosed cardiac disease. Cardiac disease in pregnancy can present as heart failure, arrhythmias or sudden death, and ischemia. Pre-existing cardiac disease can be the result of congenital heart disease, valvular heart disease, hypertensive heart disease, or coronary artery disease. In addition, there are unique diseases such as peripartum cardiomyopathy and rare diseases such as aortic dissection or primary coronary artery dissection, which may present with increased frequency during pregnancy.2,6,7
In Illinois, vascular events (eg, emboli and thromboses), cardiovascular disease, and hemorrhage were the most common causes of pregnancy-related mortality between 2002 and 2012.8 The purpose of this study was to estimate the role of specific cardiovascular diseases in maternal mortality in Illinois over a 10-year period, to examine demographic characteristics of women who died from cardiac-related causes, and to estimate the proportion of pregnancy-associated cardiovascular mortality that was potentially preventable.
MATERIALS AND METHODS
We performed a retrospective review of maternal cardiovascular deaths in Illinois from 2002 to 2011 using data from the Illinois Department of Public Health maternal mortality review database. The Illinois Department of Public Health identifies maternal deaths in several ways, including direct notification by the hospital where the death occurred, a death certificate checkbox indicating that the decedent had been pregnant within 1 year of death, vital records searches, newspaper articles, and obituaries. In Illinois, all known deaths of women within a year of pregnancy, irrespective of cause of death, are reviewed by regional supervising perinatal centers that monitor statewide networks of maternity hospitals. After a maternal death, an Illinois Department of Public Health staff member responsible for maternal mortality data collects all available records on the decedent including death certificate, associated birth or fetal death certificate, and medical records and enters data on decedent characteristics into a Microsoft Access database before sending the records to the perinatal center for review. The perinatal center administrator abstracts data about the case onto a standardized abstraction form to facilitate review of the case with the standing mortality and morbidity review committee at the hospital of death using the maternal mortality review form. The maternal mortality review form includes demographics such as race or ethnicity and age, characteristics of the pregnancy and delivery or termination, the committee's determination of the cause of death as related to the pregnancy, and their assessment of potential preventability of the death. After the review, data from the portion of the maternal mortality review form are entered into the database. Before a case review is considered complete, the Illinois Department of Public Health staff member rechecks the database against the form and any conflicting or implausible data points are corrected in consultation with the perinatal center. The process of perinatal center review has been described in greater detail elsewhere.8,9
The perinatal center that reviewed the death assessed whether the death was potentially preventable and identified any health care provider, system, or patient factors that contributed to the potential preventability of death. Preventability was defined as any action or inaction on the part of the health care provider (including physicians, nurses, anesthetists, and any other health care provider of care to pregnant or postpartum women), system, or patient that may have caused or contributed to the progression to death.10 Health care provider factors included incomplete or inappropriate management, delay in diagnosis or delay in treatment, or failure to identify patient as high risk. Systems factors included staff knowledge or training deficits, delay in blood product administration, poor charting, and failure to refer patients. Patient factors included alcohol or substance abuse, smoking, failure to seek care, and noncompliance with treatment.
In previous studies using this database, we defined cause of death as the single cause identified from a prepopulated list of common causes of maternal death found on the second page of the maternal mortality review form.8,9 For this analysis, we used the International Classification of Diseases, 9th Revision (ICD-9) diagnosis codes for the immediate and up to three underlying causes of death listed in the “Evaluation of Death” section on page 1 of the maternal mortality review form. These ICD-9 codes are identified during the course of case review and may reflect the death certificate, autopsy results, or the clinical judgment of the committee based on in-depth review of the medical records. Because the ICD-9 codes include underlying causes in addition to the immediate cause of death, this method allowed us to assess for cardiovascular causes that gave rise to the mortality even if they were not the immediate cause of death. Cardiovascular death was defined as deaths with ICD-9 codes beginning with 394, 401, 414, 424, 425, 430–434, 435, or 441 and specific codes 642.0–642.7, 642.9, 648.5–648.6, 648.8, 671.4, 674.0, and 674.5 for immediate or underlying cause of death on the maternal mortality review form (see Appendix 1, available online at http://links.lww.com/AOG/A943, for specific ICD-9 codes). In accordance with the Centers for Disease Control and Prevention, we define pregnancy-related deaths as “the death of a woman while pregnant or within 1 year of pregnancy termination—regardless of the duration or site of the pregnancy—from any cause related to or aggravated by the pregnancy or its management, but not from accidental or incidental causes.”1 Among pregnancy-related mortality, deaths were considered directly attributable to pregnancy if related to the pregnancy itself (such as preeclampsia, postpartum hemorrhage, or peripartum cardiomyopathy) and considered indirectly related to pregnancy if attributed to confounding effects of pregnancy on pre-existing maternal medical conditions such as pre-existing cardiac disease or intracranial aneurysm.11 Deaths were considered unrelated if not secondary to pregnancy (such as acute pulmonary edema secondary to cocaine use, motor vehicle accident, or homicide).
The pregnancy-associated cardiovascular mortality rate was defined as the number of women who died from a cardiovascular-related cause during pregnancy up until within 1 year after the pregnancy's completion regardless of the duration or site of pregnancy or reason for pregnancy termination divided by the corresponding number of live births in Illinois during the study period multiplied by 100,000. We calculated the pregnancy-associated cardiovascular mortality rate overall and by age group and racial or ethnic group and we used Poisson regression to estimate rate ratios with 95% confidence intervals (95% CIs). It was neither appropriate nor possible to calculate mortality rates by timing of death, relation to pregnancy, or preventability because there are no corresponding categories of live births for those characteristics. We used χ2 and Fisher exact tests to compare preventable factors cited in potentially preventable deaths secondary to cardiovascular etiology with those cited in potentially preventable noncardiac deaths. We used SAS 9.3 for all data analysis. Because all of the women in the maternal mortality review database are deceased, the institutional review boards at the Illinois Department of Public Health and the University of Illinois at Chicago determined that this research did not involve “human subjects” as defined in 45 CFR 46.102(f).
There were 636 deaths in Illinois from 2002 to 2011 of women who were pregnant or within 1 year of pregnancy for an overall death rate of 37.1 per 100,000 live births. Of these, 140 (22.0%) were cardiovascular in origin. The overall pregnancy-associated cardiovascular mortality rate was 8.2 (95% CI 6.9–9.6) deaths per 100,000 live births. There were 1,712,700 live births during the study period.
The characteristics of women who died in Illinois from cardiac and noncardiac causes are presented in Table 1. Compared with women who died from other causes (noncardiac), a greater proportion of women who died of cardiac causes were older than 30 years of age (55.0% compared with 41.1%, P=.04), within 6 weeks postpartum (56.7% compared with 49.2%, P<.01), and died as the direct or indirect result of pregnancy (66.7% compared with 27.6%, P<.01).
In Illinois, cardiac mortality rose as women aged; women aged 30–39 years died of cardiac causes at almost twice the rate of women aged 20–29 years (rate ratio [RR] 1.67, 95% CI 1.16–2.41) and the rate increase was nearly fourfold in women aged 40 years and older (RR 3.78, 95% CI 1.97–7.24). Non-Hispanic black women died from cardiovascular causes at three times the rate of non-Hispanic white women (RR 3.1, 95% CI 2.14–4.48). There were no statistical differences in cardiac mortality rates among Hispanic, non-Hispanic white, and Asian women.
Acquired heart disease was the predominant etiology of maternal cardiovascular mortality in the Illinois population (n=136 [97.1%]). Cardiomyopathy was the most common etiology (n=39 [27.9%]) followed by stroke (n=32 [22.9%]), hypertension-related deaths (n=18 [12.9%]), arrhythmias (n=15 [10.7%]), and coronary artery disease (n=13 [9.3%]). Of the 39 women who died of cardiomyopathy, 12 (30.8%) were designated as peripartum cardiomyopathy (specifically stated as peripartum cardiomyopathy or ICD-9 code 674.5); and 14 (35.9%) women were listed as cardiomyopathy without determination of etiology (data not shown). Valvular heart disease and dissections were rarer, accounting for only 7.2% of deaths combined. Congenital heart disease was rare, the etiology in only four patients (2.9%). Specific distribution of cardiovascular etiology is shown in Appendix 2, available online at http://links.lww.com/AOG/A943.
Comparison of women who died from cardiomyopathy in contrast to other cardiovascular etiologies is shown in Table 2. Women with cardiomyopathy were more likely to be younger than women who died of other cardiovascular causes (P=.02). Cardiomyopathy-associated deaths were significantly more likely to be considered directly related to pregnancy (P<.01) than other cardiac etiologies. Women younger than 20 years of age had more than three times the rate of cardiomyopathy mortality compared with women aged 20 to 29 years (RR 3.38, 95% CI 1.38–8.27). Non-Hispanic black women died of cardiomyopathy at four times the rate of non-Hispanic white women (RR 4.06, 95% CI 2.08–7.93).
Of the 140 cardiac deaths, 39 (28.1%) were classified as potentially preventable. Factors contributing to potentially preventable cardiac-related and noncardiac deaths are shown in Table 3. Incomplete, delayed, or inappropriate diagnosis or treatment were the more commonly cited among cardiac-related deaths compared with noncardiac-related deaths (n=19 [48.7%] and n=37 [19.2%], respectively; P<.01). Health care provider failure to refer the patient for a higher level of care was also more commonly cited among potentially preventable cardiac-related deaths than among women who died of noncardiac-related causes (15.4% compared with 3.1%; P<.01). Cardiac-related deaths were also more likely to be associated with patient noncompliance with treatment (35.9% compared with 6.7%, P<.01), smoking (20.5% compared with 6.7%, P<.01), obesity (12.8% compared with 1.0%, P<.01), and too few prenatal visits (10.3% compared with 2.6%, P=.02) than noncardiac deaths.
We found that more than one fifth of all pregnancy-associated deaths in Illinois were the result of cardiovascular causes, a pregnancy-associated cardiovascular mortality rate of 8.2 deaths per 100,000 live births, similar to that noted in other research.12 Cardiomyopathy was also the most common etiology of cardiovascular death. More than half of the cardiovascular deaths occurred in the first 6 weeks postpartum and were pregnancy-related.
In our study, the preponderance of cardiovascular deaths in the older population is especially striking given that only 40.1% of births occurred in women older than age 30 years of age. Increasing cardiovascular death as women aged is partly explained by the rising prevalence of cardiovascular disease in the older population, 10 per 100,000 in women aged 20–39 years old and 35.5 per 100,000 in those 40–59 years old.13
This article expands on previous research. Our analysis is based on multidisciplinary maternal mortality review, which is better positioned to assess cause of death, relation to pregnancy, and potential for prevention than assessments based on death certificate review alone.14 We also addressed risk factors for cardiovascular mortality such as advanced maternal age. Most importantly, we discovered that more than one in four maternal cardiac deaths was potentially preventable and identified aspects of care amenable to change such as monitoring patients at risk for several weeks postpartum.
Risk factors for cardiovascular disease likely play an important role in maternal cardiac mortality. Globally as well as in Illinois, rates of obesity, gestational and pre-existing diabetes, chronic hypertension, and hypertensive disorders of pregnancy have increased.15–19 In the United Kingdom, obesity was found to contribute to the risk of sudden arrhythmic death in addition to the risk of pregnancy-associated ischemia and cardiomyopathy. Analysis of the National Inpatient Sample for temporal trends in pre-existing medical conditions and obstetric complications found that women with chronic hypertension were at increased risk of developing cardiomyopathy with pregnancy.20
It is important to note that the first 6 weeks postpartum were a critical period for cardiovascular mortality in our study. In retrospective analyses of pregnancy-associated myocardial infarction and spontaneous coronary dissection, most events occurred in this timeframe (Tweet MS, Hayes SN, Gulati R, Rose CH, Best PB. Abstract 17453: clinical features of peripartum spontaneous coronary artery dissection. Circulation 2014;130).7,21 This suggests the need for more extensive postpartum care for women with hypertension, preeclampsia, or other cardiac risk factors or symptoms. Maternal early warnings have been proposed to aid diagnosis for other critical illnesses such as sepsis and hemorrhage.19 A questionnaire for women with a history of peripartum cardiomyopathy has been shown to aid in the diagnosis of heart failure recurrence.22 The Illinois Department of Public Health implemented a maternal hypertension initiative to reduce morbidity and mortality in women with hypertensive disorders of pregnancy and chronic hypertension in 2016. Development of algorithms for diagnosis of cardiovascular disease in pregnancy analogous to guidelines used to risk-stratify women with known previously diagnosed cardiovascular disease such as Cardiac Disease in Pregnancy (CARPREG study),23 ZAHARA,24 and modified World Health Organization criteria25 is an avenue for future research.
We found delays in cardiac diagnosis and initiation of therapy to be important preventable contributors to maternal cardiac mortality as have others.26 A previous retrospective analysis of peripartum cardiomyopathy found delays in 50% of patients with major adverse events.27 Delays in diagnosis may reflect in part that normal puerperal signs and symptoms can be similar to those of heart failure. Women also may not recognize they are at risk. A study of younger patients with acute myocardial infarction found that only half considered themselves at risk of heart disease and even fewer reported being told they were at risk.28 Failure to anticipate possible presence of cardiac disease may contribute to the higher mortality we found in the youngest age group.
There are some limitations to this study. The data presented are from reviews conducted by regional perinatal centers; although each center used the same review form, review processes can vary. We did not have data on the level of care at the site of delivery nor the specific level of health care provider that may be associated with potentially preventable factors. The accuracy of the perinatal center reviews in comparison with the state maternal mortality review committee was addressed in a previous publication.9 The state review committee was more likely to find that deaths were preventable and that preventability was largely the result of health care provider and system factors and fewer patient factors. Addition of a cardiologist might have clarified etiology for deaths that were not completely specified, such as “cardiac disease of pregnancy,” and refined etiology of cardiomyopathy. Illinois has had a cardiologist on the statewide committee since December 2014.
Despite our study limitations, the Illinois findings add to our understanding of cardiovascular disease as a leading contributor to maternal mortality by addressing risk factors to be assessed and that a large proportion of maternal mortality is potentially preventable by addressing issues such as the importance of monitoring patients at risk for several weeks postpartum while hemodynamic changes are still in flux. Our data support the need for more investigations into cardiovascular maternal mortality, organized communication between obstetricians and cardiologists, and the need for systems designed to better educate and communicate cardiovascular risk factors and warning signs to pregnant women and medical care providers.
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3. Knight MTDKS, Shakespeare J, Gray R, Kurinczuk JJ, editors, on behalf of MBRACE-UK. Saving lives, improving mothers' care. Surveillance of maternal deaths in the UK 2011–2013. Oxford (United Kingdom): Oxford University of Oxford, National Perinatal Epidemiology Unit, Unit NPE; 2015.
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