Clinical Outcomes of Women with Peripartum Cardiomyopathy With and Without Preeclampsia: a Population-based Study
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1 Clinical Outcomes of Women with Peripartum Cardiomyopathy With and Without Preeclampsia: a Population-based Study Isabelle Malhamé, MSc Candidate in Epidemiology, McGill University Obstetric Medicine Fellow, Brown University Natalie Dayan, Cristiano S. De Moura, Michelle Samuel, Evelyne Vinet, Louise Pilote
2 None Conflict of Interest
3 Background Preeclampsia is strongly associated with Peripartum Cardiomyopathy (PPCM) as both conditions may share a common pathophysiology 1,2 Not all women with PPCM present with co-incident preeclampsia Differences in clinical outcomes in women with PPCM with and without preeclampsia remain to be elucidated by large epidemiologic studies 1. Bello N, The relationship between pre-eclampsia and peripartum cardiomyopathy: a systematic review and meta-analysis. J Am Coll Cardiol 2013;62: Damp J, Relaxin-2 and Soluble Flt1 Levels in Peripartum Cardiomyopathy: Results of the Multicenter IPAC Study. JACC Heart failure 2016;4:380-8.
4 Objective To compare the occurrence of Major Adverse Cardiovascular Events (MACE) and death between women with PPCM and co-incident preeclampsia (peppcm) and women with PPCM without preeclampsia (PPCM) in a large population sample To compare pharmacologic treatment duration between women with peppcm and PPCM
5 Data Source A claims based administrative database from the United States: Commercial Plans and Encounters Database of the MarketScan Research Databases January 1 st, 2010 to December 31 st, 2014
6 Cohort selection: Study Population Women with obstetric deliveries No heart disease within 6 months prior to conception PPCM cases selection: ICD-9 code for PPCM Between 1 month prior to delivery and 5 months postpartum Mandatory procedure code for echocardiogram
7 Outcome Definition Major Adverse Cardiovascular Events (MACE) 1,2 Acute heart failure (including ventricular fibrillation and cardiac arrest) Pulmonary edema Acute respiratory distress Thromboembolism Puerperal cerebrovascular disorder Mechanical ventilation Mechanical circulatory support Heart transplantation Intra-cardiac device implantation Permanent pacemaker implantation Conversion of cardiac rhythm In-hospital death Within 6 months from diagnosis of PPCM 1. Sigakis MJ et al. The Validity of Discharge Billing Codes Reflecting Severe Maternal Morbidity. Anesthesia and analgesia. 2.Kolte D et al. Temporal trends in incidence and outcomes of peripartum cardiomyopathy in the United States: a nationwide population-based study. J Am Heart Assoc.
8 Treatment Duration Duration of guideline-based pharmacologic therapy for heart failure From initial prescription until discontinuation of medication
9 Statistical Methods Log binomial regression for relative risk (RR) of MACE and 95% confidence intervals (CI) Adjusted for advanced maternal age, multiple pregnancy, chronic hypertension, obesity, and diabetes mellitus (type 1, type 2, and gestational combined) Kruskal-Wallis test for significance between treatment duration in days Two-sided significance level 0.05
10 Flow Diagram Obstetric deliveries n = 1,557,409 Women no known cardiac disease n= 1,028,488 Total PPCM cases n= 804 peppcm n= 281 PPCM n = 523
11 Baseline Characteristics peppcm N= 281 PPCM N= 523 p Value* Timing of diagnosis in days (mean [sd]) 17.3 (31.0) 24.4 (38.6) Mean age (mean [sd]) 31.8 (6.7) 31.9 (5.7) 0.77 Age above 35 years 107 (38.1%) 182 (34.8%) 0.65 Multiple pregnancy 39 (13.9%) 39 (7.5%) <0.01 Gestational diabetes 85 (30.2%) 106 (20.3%) <0.01 Type 1 diabetes 7 (2.5%) 2 (0.4%) 0.01 Type 2 diabetes 38 (13.5%) 51 (9.8%) 0.10 Obesity 98 (34.9%) 125 (23.9%) <0.01 Chronic hypertension 198 (70.5%) 178 (34.0%) <0.01 Chronic kidney disease 17 (6.0%) 9 (1.7%) <0.01 Systemic autoimmune rheumatic disease + 5 (2.5%) 13 (1.8%) 1 *Comparing peppcm and PPCM
12 Frequency (%) Results peppcm PPCM Individual MACE components *p value <0.05 MACE = Major Adverse Cardiovascular Events
13 Results peppcm n(%) PPCM n(%) MACE 121 (43.1%) 162 (31.0%) Death 1 (0.4%) 6 (1.1%) Crude RR 95% CI Adjusted RR 95% CI MACE 1.39 (1.15, 1.67) 1.27 (1.04, 1.55) Death 0.31 (0.02, 1.80) There was a 27% increased risk of MACE in women with peppcm compared to women with PPCM
14 Treatment Duration Group Patients treated Median (days) IQR p Value Loop Diuretics Mineralocorticoid Receptor Antagonists Angiotensin Converting Enzyme Inhibitors Beta-Blockers Nitroglycerine- Hydralazine Angiotensin Receptor Blockers peppcm 81 (28.9 %) PPCM 104 (19.9 %) peppcm 31 (11.0 %) PPCM 33 (6.3 %) peppcm 96 (34.2 %) PPCM 107 (20.5 %) peppcm 113 (40.2 %) PPCM 142 (27.2 %) peppcm 6 (2.1 %) PPCM 6 (1.1 %) peppcm 7 (2.5 %) PPCM 15 (2.9 %)
15 Summary We found an overall higher incidence of MACE in women with co-incident preeclampsia This was mostly driven by a higher incidence of acute heart failure and pulmonary edema Despite this, there may be a lower mortality risk for women with co-incident preeclampsia Duration of therapy with ACEI may be longer for women without preeclampsia, possibly reflecting a longer time to recovery
16 Discussion Other studies in different geographic settings with smaller sample sizes have also reported worse initial outcomes for women with co-incident preeclampsia 1,2,3 This may be explained by several mechanisms: Distinctions in left ventricular remodeling seen on echocardiography 3 peppcm concentric remodeling PPCM eccentric remodeling Preeclampsia is associated with increased afterload and increased capillary permeability independently from PPCM The long term prognosis of women with preeclampsia may however be better, with shorter time to LVEF recovery 1,2,3,4 1. Ntusi NB, PloS one Ersboll AS, European journal of heart failure Lindley KJ, Circulation Heart failure Barasa A, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2017:1-8.
17 Discussion Strength: Large population sample Strict selection criteria for PPCM Indicators of morbidity validated in pregnancy Limitations: Retrospective study Administrative database Generalizability limited to insured women in US Clinical parameters lacking
18 Conclusion Our findings lend further support to the notion that peppcm and PPCM present important distinctions within the PPCM syndrome 1,2 Future studies are warranted to determine whether preeclampsia affects the efficacy of novel therapies and patients long term prognosis 1. Lindley KJ, Mann DL. Impact of Preeclampsia on Clinical and Functional Outcomes in Women With Peripartum Cardiomyopathy. Circulation Heart failure Bauersachs J. Poor Outcomes in Poor Patients?: Peripartum Cardiomyopathy-Not Just Black and White. JAMA cardiology 2017
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