Acute myocardial infarction (AMI) during pregnancy is an uncommon but potentially devastating complication of the gravid state. Acute myocardial infarction occurs during pregnancy with an incidence of approximately 3 to 10 cases per 100,000 deliveries1, 2, 3, 4 and is associated with 5% to 7% maternal case-fatality rate with grave risks to the developing fetus.2, 3 Hormonal and hemodynamic changes in the cardiovascular system and the hypercoagulable state of pregnancy in part account for the increased risk of AMI during pregnancy, which occurs with a frequency approximately 3- to 4-fold higher than that for nonpregnant women of childbearing age.5 In addition, previous population-based studies reported that maternal age, tobacco use, hypertension, diabetes mellitus, and thrombophilia are independent risk factors associated with AMI during pregnancy.2, 3Investigation of AMI during pregnancy or the puerperium has been particularly challenging because of low incidence of events and heterogeneous clinical presentations. Consequently, recent epidemiology and data on the contemporary approaches to the management of AMI during pregnancy are limited. We analyzed hospital admissions from a large national database to evaluate trends in the incidence, in-hospital management, and outcomes of AMI complicating pregnancy and the puerperium in the United States.
Discussion
In this analysis of a large national administrative database, AMI occurred in 1 of every 12,400 hospitalizations during pregnancy and the puerperium overall and in 1 of every 46,921 hospitalizations for labor or delivery. Acute myocardial infarction during pregnancy was independently associated with advanced maternal age, tobacco use, hypertension, dyslipidemia, diabetes mellitus, known heart failure, anemia, and malignancy. The frequency of AMI diagnoses during pregnancy and the puerperium increased over time because of an increase in NSTEMI diagnoses. Acute myocardial infarction during pregnancy was strongly associated with increased in-hospital mortality in both unadjusted and multivariable-adjusted analyses. Mortality rates in patients with pregnancy-related AMI remained stable over time at 4.5%.
The increasing incidence of AMI complicating pregnancy is remarkable, as it occurred despite advances in reduction of cardiovascular risk over the past decade. There are a number of plausible explanations for these trends. Greater numbers of patients with advanced maternal age may underlie some of the trends in AMI reported in this analysis, as the mean age at hospitalization for labor and delivery increased over time. In the present study and in previous reports, advanced maternal age is strongly associated with AMI during pregnancy, with up to a 30-fold increased odds in women 40 years or older in comparison to pregnant women younger than 20 years.3, 5 Still, in the present analysis, there was a significant increase in rates of AMI over time after adjustment for age and race (P<.001). Increases in AMI diagnoses during pregnancy may also be related to changes in the prevalence of cardiovascular risk factors or the frequency of cardiac biomarker screening during hospitalization for pregnancy and the puerperium. Improved diagnosis of NSTEMI with higher-sensitivity cardiac biomarker assays and increasing provider awareness of AMI in women may also be related to the observed findings.
Mechanisms of AMI during pregnancy are uncertain. In many cases, AMI may be due to conventional acute coronary syndromes. Traditional risk factors, including tobacco use, hypertension, and diabetes, are independently associated with the risk of AMI during pregnancy.2, 3, 7 As women of childbearing age are generally perceived to be at low cardiovascular risk, preexisting ischemic heart disease may be underdiagnosed in this population. Young women with occult CAD may be less likely to receive intensive management of uncontrolled risk factors.8, 9, 10, 11 However, in many cases, AMI may be independent of conventional cardiovascular risk factors. The hypercoagulable state of pregnancy increases the risk of thrombotic coronary syndromes because of increases in fibrinogen and other coagulation factor concentrations coupled with diminished fibrinolysis.12 Substantial increases in the circulating sex hormones estrogen and progesterone, changes in hemodynamics, hemodilution, and increases in cardiac output during pregnancy can lead to progressive connective tissue weakening, increased vascular shear stress, and spontaneous coronary artery dissection (SCAD).13, 14, 15 In the present analysis, coronary dissection was documented in 15% of all AMI cases, although previous case series suggest that dissection may occur in up to 40% of AMI cases during pregnancy.5, 7, 16 Consequently, SCAD has been frequently cited as a key etiology of AMI during pregnancy and the puerperium.17 The modest frequency of SCAD in the present analysis may reflect underrecognition or undercoding of this important diagnosis. Therefore, the true incidence and outcomes of SCAD during pregnancy warrant further exploration.
In this cohort, cesarean sections were associated with a higher frequency of AMI than were vaginal deliveries, another important finding that warrants further study. We were not able to assess the potential contributions of hemodilution, anemia, tachycardia, hypertension, surgical stressors, and other mismatches in myocardial oxygen supply and demand during pregnancy in relation to type 2 AMI.18
The optimal management of AMI during pregnancy remains uncertain. Based on the European Society of Cardiology guidelines, coronary angiography and PCI are the preferred strategies for patients with STEMI during pregnancy (class I, level of evidence C) and invasive management should also be considered for patients with NSTEMI and high-risk features (class IIa, level of evidence C).12 An analysis of outcome data from 1992 to 1995 and from 1995 to 2005 time periods revealed a marked increase in the rates of PCI (from 2% to 42%) and a concomitant decrease in the rates of maternal mortality (from 20% to 11%), suggesting an association between invasive management and improved mortality.5 However, in the present analysis, nearly half of women with AMI complicating pregnancy were managed conservatively. This may be related to concerns about potential complications of coronary angiography and PCI during pregnancy, radiation risks to the mother and fetus, or a perception that atherosclerotic cardiovascular disease is not anticipated in women of childbearing age. Although coronary angiography is necessary to establish a diagnosis of SCAD, PCI in this setting is associated with a high rate of complications and should be reserved for select patients with ischemia refractory to medical therapy.17 Lower-than-expected invasive management of women with AMI during pregnancy and the puerperium may also relate to uncertainty about the safety of drug-eluting stents or periprocedural anticoagulation and antiplatelet therapy in this setting. Low-dose acetylsalicylic acid is considered relatively safe during pregnancy. Thienopyridines are classified by the US FDA as pregnancy category B, although there is insufficient evidence to establish long-term safety during pregnancy. Furthermore, antiplatelet and anticoagulant therapies are associated with a risk of peripartum hemorrhage. Other guideline-directed medical therapies for cardiovascular risk reduction, including angiotensin-converting enzyme inhibitors (US FDA pregnancy category D) and statins (US FDA pregnancy category X), are contraindicated during pregnancy because of the risk of harm to the fetus.19
In-hospital mortality of 4.5% in the present analysis is similar to mortality in previously published reports.3 The maternal case-fatality rate after AMI was highest during the peripartum period and lower in the antepartum and postpartum periods.2, 5 This finding may be related to bleeding risks associated with labor and delivery that may preclude the use of preferred medical and percutaneous therapies for AMI.
There are several limitations to the present analysis. First, trimester of pregnancy could not be determined from this large administrative data set, nor could the sequence of AMI and delivery when both events occurred during the same hospital admission. Similarly, the duration of the postpartum period is not specified by ICD-9codes and could not be definitively established for this analysis, although it is conventionally defined as the 6-week period after delivery. However, thrombotic risks may persist beyond this 6-week time period.20 Second, because of the limitations of ICD-9 coding data from a national hospital data set, detailed findings from coronary angiography were not available for patients who underwent invasive management. As such, the frequency of atherosclerotic plaque rupture, intraluminal thrombus formation, coronary artery dissection, and coronary artery spasm could not be determined from these data. Similarly, the incidence of specific comorbidities associated with coronary artery dissection, such as fibromuscular dysplasia, was also not available. Rates of coronary dissection in this cohort were lower than those reported in a small series of AMI during pregnancy.7 Because many women did not undergo coronary angiography for AMI in the present study, underascertainment of coronary dissection is possible. Third, in-hospital medical management was not recorded in this administrative data set and was not available for the present analysis. Fourth, there is potential for undercoding and miscoding from administrative data sets, especially for cardiovascular risk factors and comorbidities in patients with and without AMI during pregnancy. Changes in ICD-9 coding over time may have also affected the study findings and represent an unavoidable limitation of an analysis of a large administrative database. Fifth, treatment patterns may have evolved substantially over the 13-year time period used for the present analysis. Specifically, increasing recognition of the ischemic risks during pregnancy, greater sensitivity of cardiac biomarkers, and improvements in PCI may have affected the present findings. As a consequence, definitive statements regarding the benefit of invasive therapy in this small cohort identified over a long time period may be unreliable. Sixth, although maternal in-hospital mortality was reported in the present study, fetal and newborn outcomes were not available. Finally, the study findings were derived from the US population and may not be generalizable to other cohorts.
Conclusion
In a large national database from the United States, AMI occurred in 8.1 cases per 100,000 hospitalizations during pregnancy and the puerperium. Overall, 53% of patients with AMI during pregnancy underwent invasive management and 25% underwent coronary revascularization. Invasive management was independently associated with lower mortality. Despite contemporary management strategies, maternal mortality rates remained high.
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