Trends and Outcomes of Mechanical Circulatory Support in Peripartum Women, 2002-2014: A Nationwide Inpatient Sample Analysis

ARTICLE IN PRESS Journal of Cardiothoracic and Vascular Anesthesia 000 (2019) 16

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Original Research

Trends and Outcomes of Mechanical Circulatory Support in Peripartum Women, 2002-2014: A Nationwide Inpatient Sample Analysis ,1

Elizabeth K. Cotter, MD*,x , Jennifer Banayan, MD*,z, Avery Tung, MD*, Atul Gupta, MD*, Ariel Mueller, MAy, Sajid Shahul, MD* *

Department of Anesthesia and Critical Care, University of Chicago Medical Center, Chicago, IL Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA z Northwestern University, Department of Anesthesiology, Chicago, IL x Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS

y

Objectives: To systematically explore the relationship among the use of mechanical circulatory support (MCS), the timing of placement, and outcomes in pregnancy. Design: Using the National Inpatient Sample and National Readmissions Database, the authors performed a retrospective, cohort analysis of peripartum women who received MCS. Setting: United States hospitals. Participants: A weighted sample of women who received MCS during the antepartum, delivery, or postpartum period between 2002 and 2014. Interventions: MCS Measurements and Main Results: There were 1,386 women who received MCS during their admission. These women were older and had more comorbidities than women without MCS. The mean time from admission to device placement was 5.4 days for all women, and MCS use was highest in urban teaching hospitals. Overall, peripartum use of MCS has increased since 2002, but mortality did not change during the same period. After adjusting for potential confounders, the odds ratio for mortality when MCS was placed within 6 days of admission was 0.48 (95% confidence interval 0.23-0.98) with the adjusted probability of death rising from 18.6% to 32.5% when the device was placed on or after day 6. Conclusions: Similar to trends in the general population, use of MCS has increased in the peripartum period. Women receiving MCS were generally older and had more comorbidities than those not receiving MCS. Increased time to device placement may worsen mortality. Further research will help identify appropriate candidates and factors that improve survival. Ó 2019 Elsevier Inc. All rights reserved. Key Words: Mechanical Circulatory Support; IABP; ECMO; pregnancy

PERIPARTUM CARDIAC complications account for 41% of all maternal deaths in the United States.1 In parturients with cardiogenic shock from peripartum cardiomyopathy, amniotic fluid embolism, and pulmonary emboli, mechanical circulatory support (MCS) devices are increasingly used. Such devices include intra-aortic balloon pumps (IABP), veno-venous and The authors received no financial support for this manuscript. 1 Address reprint requests to Elizabeth K. Cotter, MD, Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS 66160. E-mail address: [email protected] (E.K. Cotter). https://doi.org/10.1053/j.jvca.2019.11.047 1053-0770/Ó 2019 Elsevier Inc. All rights reserved.

veno-arterial extracorporeal membrane oxygenation (ECMO), left ventricular assist devices, and paracorporeal ventricular assist devices (PVAD).2-4 Respiratory syndromes exacerbated by pregnancy, such as influenza-induced acute respiratory distress syndrome, are also potentially treatable using MCS. More than 15 case reports have been published on the use of veno-venous ECMO in pregnant women with H1N1 associated acute respiratory distress syndrome.5 The use of MCS devices has increased dramatically in the past decade.6,7 A 2015 analysis of the National Inpatient

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Sample (NIS) Database found a 433% increase in ECMO use in the general population from 2006-2011.6 A report by the Extracorporeal Life Support Organization corroborated this finding7 and added that the increase in ECMO use was greatest in adults with respiratory failure. Survival to discharge in adults treated with MCS has also improved over time. In 2015, survival rates were 57% and 42% for respiratory and cardiac failure, respectively.7 Little data describe the incidence of, risk factors for, and outcomes associated with MCS use in the peripartum period. Case reports of ECMO use during pregnancy and post partum report maternal survival rates around 80%.5,8,9 However, these reports likely suffer from selection bias. The timing of mechanical support device placement could also impact survival. Studies of postcardiotomy shock suggest that early MCS placement may improve survival,10 and the American College of Cardiology Consensus Statement on Percutaneous Mechanical Circulatory Support recommends early mechanical support in patients who fail to improve quickly after initial interventions.11 No large studies have systematically examined the relationship among the use of MCS, the timing of placement, and the outcomes in pregnancy. The authors hypothesized that the trend toward increased use of mechanical support in nonpregnant patients would also be observed in peripartum patients and that MCS placement early in the hospital course would decrease peripartum mortality. To test this hypothesis, the authors analyzed data from the NIS. They also analyzed data from the Nationwide Readmissions Database (NRD) to examine the rate and major causes of readmissions among parturients who underwent MCS. Both large, national, administrative databases record the incidence, outcomes, comorbidities and readmission rates for patients who receive MCS during the peripartum period. Materials and Methods Data Source and Study Population The need for internal review board approval was waived for this study. The data that support the findings of this study are available from the National Inpatient Sample (NIS) and National Readmissions Database (NRD), but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are available from the authors upon reasonable request and with permission of the NIS and NRD. The authors performed a retrospective cohort analysis using the 2002-2014 NIS and the 2014 NRD. The NIS database is administered by the The Healthcare Cost and Utilization Project (HCUP) and provides discharge billing data on approximately 8 million inpatient stays annually.12 The NIS uses a stratified framework (based on ownership/control, bed size, teaching status, urban/rural location, and region) to sample 20% of all participating hospitals (N = 4,924 in 2013) and weights the sample to produce data estimates for 95% of all inpatient hospitalizations in the U.S. The authors’

methodology accounted for the 2012 change in NIS design with more stable and precise estimates than previous versions. The NIS data set includes demographic information, comorbidities, principal and secondary diagnoses and procedures, inpatient mortality, and disposition. NRD 2014, like the NIS, is a HCUP-maintained inpatient database of 21 participating states. The NRD data are weighted to estimate national trends.13 Unweighted, the NRD 2014 consists of approximately 14 million discharges. The weighted database represents approximately 26 million discharges nationwide. Each patient is assigned a unique de-identified linkage number to track discharges from initial and subsequent admissions. The authors identified women who were hospitalized during the antepartum, delivery, or postpartum periods. Antepartum hospitalizations were identified using clinical classification software categories developed by the HCUP, which groups International Classification of Disease-ninth revision (ICD-9) diagnoses into clinically relevant categories. Maternal hospitalizations for delivery were identified using a previously validated method employing ICD-9 codes.14 Postpartum hospitalizations were identified utilizing a previously published NIS algorithm encompassing 3 separate methods. First, the authors searched for discharges with the fifth digit subclassification of “4” in primary or secondary diagnosis ICD-9 codes, representing postpartum encounters. Second, a code for postpartum care after delivery (ICD-9 V24) was identified. Third, they searched for postpartum diagnosis related group codes: 376 or 377 for years 2002-2007, 776 or 769 for years 2008-2013. The authors examined all women aged 15-44 years who received any MCS during the delivery hospitalization. The authors defined MCS as an intraortic balloon pump (ICD-9 code 37.61), veno-arterial or veno-venous ECMO (ICD-9 39.65, 37.62), left ventricular assist device (ICD-9 37.66), and PVAD (ICD-9 37.68). Time to device placement was determined by using procedure codes for MCS placement and calculated as the amount of time passed from admission to placement of the device. NIS defines this code as “PRDAY” which is time from hospital admission to procedure. Each patient in the database may have up to 25 ICD-9 codes. In an effort to reduce confounding, the authors individually examined each entry to ensure that the primary reason for admission was delivery or worsening cardiac or respiratory failure. Use agreements prevent the reporting of conditions with fewer than 10 occurrences per year to prevent patient identification. Exposure, Outcome, and Covariates To evaluate the effect of time to MCS on inpatient mortality, the authors created a multivariable logistic regression. In their model, the exposure of interest was whether time to MCS was greater or less than 6 days. In pregnant women with cardiogenic shock, the authors’ previous work has shown decreased odds of death when MCS was placed within 6 days of admission.4 The primary outcome was inpatient mortality during the same delivery hospitalization. Potential confounders in this model included known risk factors for maternal mortality during delivery, such as age, mode of delivery, and surrogates for socioeconomic

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status (median household income per zip code of residence and insurance status: Medicare, Medicaid, private insurance, selfpay, no charge, and other). To adjust for the presence and severity of comorbid conditions, the authors used the Bateman Comorbidity Index which has been specifically validated in obstetric patients to predict severe maternal morbidity or mortality.15,16 Variables integrated in the index include severe preeclampsia/eclampsia, pulmonary hypertension, multiple gestation, placenta previa, and previous cesarean section. The variables are weighted based on their likelihood of contributing to acute maternal end-organ injury or death. To identify comorbidities, the authors used a comprehensive set of validated measures developed for use with the NIS.17 The ICD-9 codes in this study can be found in Appendix 1. Statistical Analysis Analyses were performed using SAS 9.4 (SAS Institute, Cary, NC) and SUDAAN 11.1 (Research Triangle Institute, Research Triangle Park, NC). The authors weighted estimates to adjust for design effects of the sampling. Categorical variables were presented as frequencies or proportions and compared using the chi-squared test. Univariate and

multivariable logistic regression models were constructed to test the association between time to MCS and mortality. All tests were two-sided and p values below 0.05 were considered statistically significant. Results Demographics and Patient Characteristics The authors identified 1,386 women (weighted) who received MCS during their admission. Demographic data appear in Table 1. Of patients who received MCS, 55.7% were older than 25 years (p < 0.001). The most common payers were Medicaid and private insurance, and median household incomes did not differ between patient groups. Of MCS devices, 80.9% were placed in urban, teaching hospitals. No region of the country placed more mechanical devices than any other. Overall, women receiving MCS had more comorbidities (Table 2) than women not receiving the intervention. They were Table 2 Maternal Comorbidities Weighted N (%)

Table 1 Patient Demographics Weighted N (%) No Mechanical Support

Mechanical Support

Number of Patients 57,401,102 1,386 Age (years) N (%) N (%) 15-24 35,239,890 (61.38) 613(44.24) 25-34 22,022,186 (38.36) 710 (51.2) 35 + 149,545 (0.26) 63 (4.55) Race White 24,146,590 (51.71) 515 (46.49) Black 6,809,731 (14.58) 373 (33.64) Hispanic 10,821,593 (23.18) 136 (12.31) Asian or Pacific Islander 2,302,243 (4.93) 29 (2.66) Other 2,260,473 (4.84) 50 (4.49) Median Household Income for Patient’s Zip Code (percentile) 0-25th 14,458,124 (27.86) 405 (30.97) 26th-50th 13,109,620 (25.26) 355 (27.12) 51st-75th 12,622,067 (24.32) 288 (21.98) 76th-100th 11,705,507 (22.56) 261 (19.93) Primary Expected Payer Medicare 414,238 (0.72) 126 (9.12) Medicaid 24,288,517 (42.38) 613 (44.39) Private Insurance 28,959,352 (50.52) 552 (40.01) Self-Pay 1,984,255 (3.46) 37 (2.67) Other 1,543,071 (2.69) 53 (3.81) Hospital Characteristics Teaching Status Rural 6,446,263 (11.28) 48 (3.46) Urban Nonteaching 23,158,454 (40.51) 216 (15.67) Urban Teaching 27,563,103 (48.21) 1,117 (80.87) Region of Hospital Northeast 9,468,927 (16.49) 196 (14.17) Midwest or Northcentral 12,186,172 (21.23) 344 (24.8) South 21,742,531 (37.87) 562 (40.56) West 14,013,991 (24.41) 284 (20.47)

p Value

<0.001

<0.001

0.46

<0.001

<0.001

0.33

3

Number of Patients Patient Comorbidities Hypertension Congestive Heart Failure Valvular Disease Pulmonary Circulation Disorders Paralysis Other Neurologic Disorders Chronic Pulmonary Disease Obesity Hypothyroid Alcohol Abuse Chronic Anemia Iron Deficiency Anemia Sepsis Drug Abuse Diabetes Without Chronic Complications Diabetes With Chronic Complications Collagen Vascular Disease/ Rheumatoid Arthritis Renal Failure Liver Disease Peripheral Vascular Disorders Peripartum Cardiomyopathy Preeclampsia Severe Preeclampsia Eclampsia Pulmonary Embolism/Deep Venous Thrombosis Depression Psychoses Weight Loss

No Mechanical Support

Mechanical Support

p Value

57,401,102

1,386

1,232,604 (2.16) 66,376 (0.12) 285,953 (0.5) 25,579 (0.04)

260 (18.82) 418 (30.28) 158 (11.42) 123 (8.92)

<0.001 <0.001 <0.001 <0.001

27,587 (0.05) 339,454 (0.59) 1,859,293 (3.25) 1,862,783 (3.26) 1,071,168 (1.87) 91,937 (0.16) 5,077,272 (8.89) 3,888,581 (6.81) 33,699 (0.06) 892,428 (1.56) 622,759 (1.09)

10 (0.71) 59 (4.3) 111 (8.04) 138 (10.03) 66 (4.76) 0 241 (17.43) 236 (17.12) 177 (12.74) 58 (4.17) 87 (1.43)

0.18 0.006 0.006 <0.001 0.04 <0.001 <0.001 <0.001 <0.001 0.028 <0.001

79,644 (0.14)

0

0.5

138,252 (0.24)

38 (2.74)

0.01

38,968 (0.07) 82,253 (0.14) 10,116 (0.02)

83 (6) 15 (1.09) 10 (0.72)

<0.001 0.13 0.17

42,581 (0.07) 1,336,634 (2.3) 654,349 (1.14) 42,994 (0.07) 115,203 (0.2)

705 (50.84) 72 (5.19) 19 (1.33) 14 (1.03) 233 (16.78)

<0.001 0.027 0.77 0.11 <0.001

1,035,541 (1.81) 456,588 (0.8) 47,505 (0.08)

85 (6.17) 24 (1.74) 141 (10.19)

0.004 0.22 <0.001

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Mortality

Table 3 Maternal Complications Weighted N (%)

Number of Patients Cardiogenic Shock Acute Myocardial Infarction Amniotic Fluid Embolism Coagulopathy Acute Respiratory Distress Syndrome Mechanical Ventilation Fluid and Electrolyte Disorders Cardiac Arrest Death

No Mechanical Support

Mechanical Support

p Value

57,401,102 1,542 (0.0) 4792 (0.01) 2,460 (0) 658,791 (1.15) 7097 (0.01)

1,386 746 (53.84) 324 (23.41) 10 (0.82) 421 (30.48) 15 (1.07)

<0.001 <0.001 0.16 <0.001 0.08

57,718 (0.1) 715,095 (0.01)

693 (50.04) 612 (44.31)

<0.001 <0.001

4,393 (0.01) 9,516 (0.02)

171 (12.37) 269 (19.4)

<0.001 <0.001

Table 4 Types of Mechanical Circulatory Support Mechanical Support Weighted N (%) Number of Patients Type of MCS ECMO IABP VAD

1,386 231 (16.65) 721 (57.18) 63 (4.55)

Abbreviations: ECMO, extracorporeal membrane oxygenation; IABP intraaortic balloon pumps; MCS, mechanical circulatory support; VAD, ventricular assist devices.

more likely to have peripartum cardiomyopathy (50.84% v 0.07%), congestive heart failure (30.28% v 0.12%), valvular disease (11.42% v 0.5%), pulmonary embolus/deep venous thrombosis (16.78% v 0.2%), or pulmonary circulation disorders (8.92% v 0.04%). MCS use was not associated with hypertensive disorders of pregnancy (specifically severe preeclampsia and eclampsia) or amniotic fluid embolism. Women with cardiogenic shock and acute myocardial infarction were also more likely to receive MCS (53.84% v 0% and 23.41% v 0.01%, respectively) (Table 3). Table 4 lists the distribution of MCS devices. The most common MCS device was an IABP (57.18%).

Of the women receiving MCS, 171 (12.37%) suffered a cardiac arrest during their admission. Overall, in-hospital mortality was considerably higher for women receiving MCS than for pregnant women who did not receive MCS (19.4% v 0.02%, p < 0.001) (Table 3). The mean time from admission to device placement was 5.4 days for all women. After adjusting for potential confounders the odds ratio for mortality when MCS was placed within 6 days of admission was 0.477 (95% confidence interval 0.233-0.979), with the adjusted probability of death rising from 18.64% to 32.45% when the device was placed on or after day 6. Trends From 2002 to 2009, MCS use during the perinatal period increased from 8.74 to 39.72 devices per million women. Since 2009, MCS use has trended downward, with 30.02 devices per million women placed in 2014 (Fig 1). Over the 12 year study period, mortality for peripartum women who received MCS rose to 42.7% in 2006 and subsequently declined to 24% in 2014. The mortality rate in 2014 did not differ from that in 2002 (Fig 2). In the 2014 NRD, the 30 day readmission rate was 11.60% among parturients who had received MCS. The most common reasons for readmission were acute pericarditis (30%), postpartum cardiovascular disease (18.41%), coagulation abnormalities (17.81%), postpartum hypertension (17.60%), and acute renal failure (16.11%). Discussion The use of MCS in pregnancy has previously been described only in case reports, series, and literature reviews.5,8,18-20 The paucity of data precludes understanding of what factors impact survival in these patients and is also reflected in the lack of guidelines on the use of MCS in pregnancy from Extracorporeal Life Support Organization or the American Congress of Obstetricians and Gynecologists. The authors show that the trend toward greater use of MCS in the adult population is also present in peripartum women and that placement of MCS

Fig 1. Peripartum MCS trends by year

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Fig 2. Peripartum MCS in-hospital mortality by year

more than 6 days after admission was associated with a higher probability of death. The authors’ observation that MCS placement increased substantially over the study period are consistent with existing literature. From 1999-2011, overall ECMO use in the United States increased >400% before declining slightly in 2014.6,21 This upward trend is coincident with the increasing availability of PVADs that facilitate MCS placement in emergent conditions.22 In contrast, since 2009 the use of peripartum ECMO has declined when compared to the general adult population.7 Although the reasons for the recent decline in MCS use in peripartum patients is not clear, the 2009 H1N1 flu epidemic in may have partly accounted for a transient spike and a subsequent decline. Alternatively, because a large proportion of MCS in this study consists of IABPs, the publication of reports questioning its utility in cardiogenic shock may also have played a role in the decline. The overall 19.4% mortality rate observed is lower than previously published mortality rates for ECMO in the adult population7 but is consistent with existing reports of ECMO in pregnancy.5,8 Possible reasons for lower mortality in peripartum ECMO are a younger age and a high incidence of potentially reversible causes such as peripartum cardiomyopathy.23 Another possible reason for a lower observed mortality in this study is the high rate of peripartum patients receiving an intraaortic balloon pump. Such patients are less critically ill than their counterparts receiving ECMO or PVADs and their inclusion in this study may have shifted the mortality rate downward. Despite a declining mortality over time for adult ECMO patients (cardiac and respiratory failure),7,24 the authors found no similar trend in mortality for MCS in pregnancy throughout the study period. This lack of improvement parallels the increasing morbidity from maternal cardiovascular disease in the United States. As the burden of disease increases, many women are presenting in more advanced stages and thus may not be salvageable with MCS. The authors also found that MCS use within 6 days of admission correlated with lower in-hospital mortality when compared with later initiation. This finding is also consistent with existing literature. In nonpregnant adults, multiple studies suggest that placement of MCS prior to initiating inotropes or

vasopressors favorably impacts survival after acute myocardial infarction or cardiogenic postcardiotomy shock.7,10 Although the authors were unable to identify precisely when the critical organ failure occurred relative to device placement, their results suggest that placing MCS earlier in the hospital course may reduce mortality in peripartum patients with cardiogenic shock or respiratory failure. As the use of such devices grows, further work will be needed to identify appropriate candidates and the factors that improve survival. The predictors of death in patients receiving short-term MCS include age, a diagnosis of cardiogenic shock, use of an IABP before additional MCS, or the need for cardiopulmonary resuscitation.23 Risk factors for mortality with MCS in pregnancy are not yet known. Not surprisingly, obstetric patients receiving MCS had more discharge diagnoses relating to cardiac and respiratory failure. Both pulmonary embolism and cardiogenic shock had a higher association with MCS. However, amniotic fluid embolism (AFE) did not, even though ECMO is an ideal treatment strategy for the most severe cases of AFE. One possible explanation is that AFE may be underreported given the difficulty in definitively making the diagnosis. This study has several limitations. Its retrospective nature does not let us comment on causality. Although the authors were able to determine the time from admission to device placement, their analysis does not allow us to determine the time from delivery or organ failure to device placement. The authors also could not determine which conditions were present before placement of MCS and which developed after. Thus, they could not determine the indication for mechanical support or the proximate cause of death. In addition, owing to the limitations of ICD-9 coding, the authors could not determine the type of device placed in each patient. For example, in ICD-9 codes, PVAD would indicate both Impella (Abiomed United States, Danvers, MA) or TandemHeart (Cardiac Assist Technologies, Pittsburgh, PA). Conclusion The peripartum use of MCS has been increasing in parallel with increases in the general population. Mortality with MCS in pregnancy is lower than in the general adult population but

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has not displayed a downward trend over time. Longer times from admission to placement of mechanical support correlated with worsened outcomes. Additional research will allow a better understanding of the epidemiology of MCS use in peripartum patients with cardiac or respiratory failure refractory to stabilization. Conflict of Interest AT is Editor of Anesthesia and Analgesia. The other authors (EC, JB, AG, AM, SS) have no competing interests to disclose. Appendix 1 ICD 9 codes for the Bateman comorbidity index; http:// www.drugepi.org/wp-content/uploads/2011/04/maternal_co morbidity_index_code_final.txt. ICD 9 codes for severe maternal morbidities: http://www. cdc.gov/reproductivehealth/maternalinfanthealth/severemater nalmorbidity.html ICD 9 codes for other comorbidities and procedures: - Russo, C.A. (Thomson Reuters), Wier, L. (Thomson Reuters) and Steiner, C. (AHRQ). Hospitalizations Related to Childbirth, 2006. HCUP Statistical Brief #71. April 2009. U.S. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcupus.ahrq.gov/reports/statbriefs/ sb71.pdf. - Stranges, E. (Thomson Reuters), Wier, L.M. (Thomson Reuters) and Elixhauser, A. (AHRQ). Complicating Conditions of Vaginal Deliveries and Cesarean Sections, 2009. - HCUP Statistical Brief #131. May 2012. Agency for Healthcare Research and Quality, Rockville, MD. Available at http://www.hcup-us.ahrq.gov/reports/statbriefs/ sb131.pdf. (Accessed March 15, 2012). - Moore JE (AHRQ), Witt WP (Truven Health Analytics), Elixhauser A (AHRQ). Complicating Conditions Associated With Childbirth, by Delivery Method and Payer, 2011. HCUP Statistical Brief #173. May 2014. Agency for Healthcare Research and Quality, Rockville, MD. http:// www.hcup-us.ahrq.gov/reports/statbriefs/sb173-Child birth-Delivery-Complications.pdf.

References 1 Creanga AA, Berg CJ, Syverson C, et al. Pregnancy-related mortality in the United States, 2006-2010. Obstet Gynecol 2015;125:5–12. 2 Pregnancy Mortality Surveillance System. vol 2017. Atlanta, GA: Centers for Disease Control; 2017.

3 Lima FV, Parikh PB, Zhu J, et al. Association of cardiomyopathy with adverse cardiac events in pregnant women at the time of delivery. JACC Heart Fail 2015;3:257–66. 4 Banayan J, Rana S, Mueller A, et al. Cardiogenic shock in pregnancy: Analysis from the National Inpatient Sample. Hypertens Preg 2017;36:117–23. 5 Moore SA, Dietl CA, Coleman DM. Extracorporeal life support during pregnancy. J Thorac Cardiovasc Surg 2016;151:1154–60. 6 Sauer CM, Yuh DD, Bonde P. Extracorporeal membrane oxygenation use has increased by 433% in adults in the United States from 2006 to 2011. ASAIO J 2015;61:31–6. 7 Thiagarajan RR, Barbaro RP, Rycus PT, et al. Extracorporeal Life Support Organization Registry International Report 2016. ASAIO J 2017;63:60–7. 8 Sharma NS, Wille KM, Bellot SC, et al. Modern use of extracorporeal life support in pregnancy and postpartum. ASAIO J 2015;61:110–4. 9 Agerstrand C, Abrams D, Biscotti M, et al. Extracorporeal membrane oxygenation for cardiopulmonary failure during pregnancy and postpartum. Ann Thorac Surg 2016;102:774–9. 10 Akay MH, Gregoric ID, Radovancevic R, et al. Timely use of a CentriMag heart assist device improves survival in postcardiotomy cardiogenic shock. J Card Surg 2011;26:548–52. 11 Rihal CS, Naidu SS, Givertz MM, et al. 2015 SCAI/ACC/HFSA/STS clinical expert consensus statement on the use of percutaneous mechanical circulatory support devices in cardiovascular care. J Am Coll Cardiol 2015;65:e7–e26. 12 Dufour P, Vinatier D, Puech F. The use of intravenous nitroglycerin for cervico-uterine relaxation: a review of the literature. Arch Gynecol Obstet 1997;261:1–7. 13 Nationwide Readmissions Database (NRD), Healthcare Cost and Utilizaiton Project (HCUP). Agency for Healthcare Research and Quality, Rockville, MD. 2013. https://www.hcup-us.ahrq.gov/nrdoverview.jsp. 14 Kuklina EV, Whiteman MK, Hillis SD, et al. An enhanced method for identifying obstetric deliveries: implications for estimating maternal morbidity. Maternal Child Health 2008;12:469–77. 15 Bateman BT, Mhyre JM, Hernandez-Diaz S, et al. Development of a comorbidity index for use in obstetric patients. Obstet Gynecol 2013;122:957–65. 16 Metcalfe A, Lix LM, Johnson JA, et al. Validation of an obstetric comorbidity index in an external population. Br J Obstet Gynecol 2015;122:1748–55. 17 Mhyre JM, Bateman BT, Leffert LR. Influence of patient comorbidities on the risk of near-miss maternal morbidity or mortality. Anesthesiology 2011;115:963–72. 18 King PT, Rosalion A, McMillan J, et al. Extracorporeal membrane oxygenation in pregnancy. The Lancet 2000;356:45–6. 19 Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: population based cohort study. Br Med J (Clin Res Ed) 2010;340: c1279. 20 Biderman P, Carmi U, Setton E, et al. Maternal salvage with extracorporeal life support: lessons learned in a single center. Anesth Analg 2017;125:1275–80. 21 McCarthy FH, McDermott KM, Kini V, et al. Trends in U.S. extracorporeal membrane oxygenation use and outcomes: 2002-2012. Semin Thorac Cardiovasc Surg 2015;27:81–8. 22 Khera R, Cram P, Lu X, et al. Trends in the use of percutaneous ventricular assist devices: analysis of national inpatient sample data, 2007 through 2012. JAMA Int Med 2015;175:941–50. 23 Arany Z, Elkayam U. Peripartum cardiomyopathy. Circulation 2016; 133:1397–409. 24 Stretch R, Sauer CM, Yuh DD, et al. National trends in the utilization of short-term mechanical circulatory support: incidence, outcomes, and cost analysis. J Am Coll Cardiol 2014;64:1407–15.