Mitral valve prolapse (MVP) is the most common valvular heart disease in women of reproductive age. Whether MVP increases the likelihood of adverse outcomes in pregnancy is unknown. The study objective was to examine the cardiac and obstetric outcomes associated with MVP in pregnant women. This retrospective cohort study, using the Healthcare Cost and Utilization Project National Readmission Sample database between 2010 and 2017, identified all pregnant women with MVP using the International Classification of Disease, Ninth and Tenth Revisions codes. The maternal cardiac and obstetric outcomes in pregnant women diagnosed with MVP were compared with women without MVP using multivariable logistic and Cox proportional hazard regression models adjusted for baseline demographic characteristics. There were 23,000 pregnancy admissions with MVP with an overall incidence of 16.9 cases per 10,000 pregnancy admissions. Pregnant women with MVP were more likely to die during pregnancy (adjusted hazard ratio 5.13, 95% confidence interval [CI] 1.09 to 24.16), develop cardiac arrest (adjusted odds ratio [aOR] 4.44, 95% CI 1.04 to 18.89), arrhythmia (aOR 10.96, 95% CI 9.17 to 13.12), stroke (aOR 6.90, 95% CI 1.26 to 37.58), heart failure (aOR 5.81, 95% CI 3.84 to 8.79), or suffer a coronary artery dissection (aOR 25.22, 95% CI 3.42 to 186.07) compared with women without MVP. Pregnancies with MVP were also associated with increased risks of preterm delivery (aOR 1.21, 95% CI 1.02 to 1.44) and preeclampsia/hemolysis, elevated liver enzymes, and low platelets syndrome (aOR 1.22, 95% CI 1.05 to 1.41). In conclusion, MVP in pregnancy is associated with adverse maternal cardiac outcomes and higher obstetric risks.
Cardiac conditions are responsible for greater than one-third of pregnancy-related deaths. As 3 of 5 pregnancy-related deaths have been deemed preventable, significant attention has been directed at identifying pregnant women at increased risk for adverse outcomes with the goal of decreasing maternal morbidity and mortality. , Mitral valve prolapse (MVP) is the most common valvular heart disease in women of reproductive age. It is estimated to affect 1% to 3% of the general population, with an unknown prevalence in pregnant women. The adverse outcomes associated with MVP range from hemodynamically significant mitral regurgitation, heart failure, and endocarditis to malignant cardiac arrhythmias and sudden cardiac death. The association between sudden cardiac death and MVP may be greater than previously suspected, occurring with an estimated annual risk as high as 2% in the general population. There are few published data about the risk of adverse cardiac outcomes associated with MVP in pregnant women, and the few published reports include a few patients. One such study indicates that women of reproductive age with MVP may be at a disproportionate risk of sudden cardiac death. Accordingly, the objective of this study was to compare cardiac and obstetric outcomes in pregnant women with MVP with pregnant women without MVP, utilizing a large database of patients.
Methods
The study population consisted of a nationally representative cohort of hospital admissions that took place between January 1, 2010 and December 31, 2017. The database was obtained from the Nationwide Readmission Database (NRD), Healthcare Cost and Utilization Project (HCUP), and the Agency for Healthcare Research and Quality dataset between 2010 and 2017. The NRD is the largest publicly available all-payer inpatient care database in the United States and contains discharge-level data from state data organizations, hospital associations, and private data organizations that participate in the HCUP project. The database provides a stratified sample of approximately 20% of discharges from HCUP-participating hospitals in the United States, representing more than 95% of the national population, and deidentified patient demographic and clinical information. This study was exempt from our Institutional Review Board review because we used a deidentified publicly available dataset.
The NRD was used to identify pregnant women who had a diagnosis of pregnancy and delivery by the International Classification of Diseases (ICD), Ninth Revision (ICD-9) and ICD, Tenth Revision (ICD-10) diagnosis codes from 2010 to 2017. We used ICD-9 and ICD-10 codes to identify patients with MVP (ICD-9 424.0 and ICD-10 I34.1). Only pregnant women ≥18 years of age were included.
We obtained baseline patient demographic, clinical, cardiac, and obstetric outcome data. Patient demographic data included age, obesity (body mass index ≥30), smoking history, location of medical care (urban vs rural), preexisting chronic hypertension, hyperlipidemia, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease/airway disease, malignancy, diabetes, and the Charlson co-morbidity index.
The primary study outcome was maternal death during the pregnancy-related admission. The secondary maternal outcomes included hospital readmission, cardiac arrest, any cardiac arrhythmia, stroke, acute congestive heart failure, myocardial infarction, coronary artery dissection, aortic dissection, thromboembolism, and endocarditis. Obstetric outcomes included Cesarean delivery, preterm delivery (before 37-week gestation), gestational hypertension, preeclampsia, hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome (a life-threatening condition of pregnancy marked by hemolysis, elevated liver enzyme levels, and low platelet levels), obstetric hemorrhage, or perinatal death. All associated ICD-9 and ICD-10 diagnosis codes are shown in Supplementary Table 1 for each outcome of interest.
The baseline characteristics of the study population were expressed as weighted values based on the prevalence of characteristics at the time of hospital discharge weights provided in the database. This weighting was performed to estimate the prevalence of the characteristics in a nationally representative sample for comparison with our data. Continuous variables with normal distribution were expressed as weighted mean ± SDs and with skewed distribution as weighted median with interquartile range. Categorical variables were expressed as weighted numbers with percentages and compared between respective comparison groups with the chi-square test and analysis of variance where appropriate for patients with and without MVP. We examined differences in inpatient mortality and hospital readmission between women with and without a diagnosis of MVP in multivariable Cox regression models adjusted for age (reference is age <35 years), elective admission, obesity, smoking status, histories of hypertension, diabetes mellitus, hyperlipidemia, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease/asthma, cancer, family history of premature coronary artery disease, urban versus rural hospital location, teaching hospital status, insurance status (could include multiple insurances), and Charlson co-morbidity index; multivariable adjusted hazard ratio with accompanying 95% confidence intervals (CIs) were calculated. For our secondary study outcomes, we computed odds ratio with 95% CI in multivariable adjusted logistic regression models adjusted for similar variables as previously mentioned. Weighted analyses were used for all statistical calculations. Statistical analysis was performed using STATA version 14.2 (StataCorp, College Station, Texas). All p values were 2-sided, with a significance threshold of p < 0.05.
Results
In a total of 13,620,427 pregnancy admissions between 2010 and 2017, there were 23,000 patients diagnosed with MVP, yielding an overall incidence rate of 16.9 cases per 10,000 pregnancy admissions. Of these, 22,996 were discharged alive and 315 women (1.4%) were readmitted within 30 days of discharge ( Figure 1 ).
The baseline characteristics of the study population are shown in Table 1 . Pregnant women with MVP were older, were less likely to be obese, have a higher co-morbidity burden, have private health insurance, and were more likely to be admitted to a teaching urban hospital.
| Mitral valve prolapse | |||
|---|---|---|---|
| Variable | Present (n= 23,000) | Absent (n= 13,597,427) | p-value |
| Age (years) | 34±6 | 30±6 | <0.001 |
| Pre-Gravid Body Mass Index ≥30 kg/m 2 | 1,384 (6.0%) | 1,118,108 (8.2%) | <0.001 |
| Current smoker | 1,024 (4.5%) | 616,142 (4.5%) | 0.74 |
| Pre-existing Diabetes | 352 (1.5%) | 178,113 (1.3%) | 0.12 |
| Pre-Existing Hypertension | 1,892 (8.2%) | 899,914 (6.6%) | <0.001 |
| Hyperlipidemia | 181 (0.8%) | 35,301 (0.3%) | <0.001 |
| Chronic kidney disease | 98 (0.4%) | 19,189 (0.1%) | <0.001 |
| Peripheral vascular disease | 54 (0.2%) | 5,407 (0.04%) | <0.001 |
| COPD/airway disease | 3,102 (14%) | 725,556 (5%) | <0.001 |
| Cancer | 57 (0.2%) | 13,192 (0.1%) | <0.001 |
| Family history of CAD | 509 (2%) | 140,398 (1.0%) | <0.001 |
| Academic Teaching hospital | 16,179 (70%) | 8,827,873 (65%) | <0.001 |
| Urban hospital | 17,374 (76%) | 9,963,151 (73%) | 0.001 |
| Charlson Score | <0.001 | ||
| 0 | 18,811 (82%) | 12,576,400 (93%) | |
| 1 | 3,471 (15%) | 923,384 (6.8%) | |
| 2 | 501 (2.2%) | 68,726 (0.5%) | |
| ≥3 | 217 (0.9%) | 28,917 (0.2%) | |
| Insurance status | <0.001 | ||
| Medicare | 363 (1.6%) | 111,673 (0.8%) | |
| Medicaid | 5,399 (24%) | 5,417,436 (40%) | |
| Private | 16,312 (71%) | 7,412,956 (55%) | |
| Self-pay | 236 (1.0%) | 233,391 (1.7%) | |
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