Lewei Duan

Atrial Fibrillation and Atrial Flutter in Pregnant Women—A Population‐Based Study

Background The goal of this study was to determine the prevalence of atrial fibrillation and atrial flutter (AF) in pregnant women and to examine the impact of AF on maternal and fetal outcomes. Methods and Results Between January 1, 2003 and December 31, 2013, there were 264 730 qualifying pregnancies (in 210 356 women) in the Kaiser Permanente Southern California hospitals, among whom AF was noted in 157 pregnancies (129 women; 61.3 per 100 000 women, or 59.3 per 100 000 pregnancies). Prevalence of AF (per 100 000 women) in white, black, Asian, and Hispanic women was 111.6, 101.7, 45.0, and 34.3, respectively. Older age was associated with higher odds of having AF. Compared to women <25 years of age, the odds ratio (OR) of AF was 4.1 in women age 30 to 34 years, 4.9 in women age 35 to 39 years, and 5.2 in women age ≥40. Odds of AF episodes were higher during the third trimester compared to the first trimester (OR, 3.2; 95% CI: 1.5–7.7). Among AF patients, adverse maternal cardiac events were rare—2 women developed heart failure and there were no strokes or systemic embolic events and no maternal death. There were 156 live births (99.4% of all pregnancies). Compared to women without AF, fetal birth weights were similar, but rate for neonates’ admission to the neonatal intensive care unit was higher (10.8% vs 5.1%; P=0.003). Conclusions AF is rare in pregnant women. Certain factors such as increased maternal age and white race increase the odds of having AF. Major maternal and fetal complications are infrequent, albeit a source of concern.

β-Blocker Exposure in Pregnancy and Risk of Fetal Cardiac Anomalies

This population-based cohort study examines the risk of fetal cardiac malformations associated with maternal β-blocker exposure.

Maternal and fetal outcomes in pregnant women with heart failure

Objectives The goal of this study is to report the prevalence, aetiology and clinical outcome of pregnant women with heart failure. Methods This is a retrospective community-based cohort study that included pregnant women in the Kaiser Permanente Health System between 2003 and 2014. Women with heart failure were identified using International Classification of Disease, Ninth Revision codes. Medical records were manually reviewed to confirm diagnosis and adjudicate outcomes. Results In a cohort of 385 935 pregnancies, 488 (0.13%) had a diagnosis of heart failure, corresponding to 126 cases per 100 000 pregnancies. Peripartum cardiomyopathy was the most common cause of heart failure, accounting for 333 (68.2%) cases. Preterm birth and caesarean delivery were more common in patients with heart failure. Neonatal death rate was higher in the heart failure group (1.0% vs 0.4%, p=0.03). Infants delivered to women with heart failure had lower birth weights (3112.0±774.0 g vs 3331.9±575.5 g, p<0.001) and lower Apgar score at 1 min (7.9±1.5 vs 8.3±1.1, p<0.001). Median follow-up was 6.2 years (IQR 3.2–9.2). During follow-up, 7 (1.4%) in the heart failure group and 423 (0.11%) in the control group died. Heart failure was associated with a 7.7-fold increase risk of death (adjusted HR 7.7, 95% CI 3.6 to 16.4, p<0.001). Conclusion Heart failure during pregnancy is associated with unfavourable fetal outcomes including prematurity and low birth weight. While the overall mortality rate was low, pregnant women with heart failure carried an excess risk of death compared with controls.

Association between encounter frequency and time to blood pressure control among patients with newly diagnosed hypertension: a retrospective cohort study

This retrospective cohort study of 95 957 patients from a large integrated healthcare organization was conducted to examine whether the frequency and intervals between outpatient encounters were associated with achieving blood pressure (BP) control. Patients were followed up until they were censored or achieved BP control up to 1 year. Additionally, this study examined the time to BP control. On average, follow‐up was significantly longer in patients with uncontrolled BP at 292.9 days compared with 232.2 days in those with BP control. The controlled BP group had significantly more encounters on average compared with the uncontrolled BP group (4.1 vs 3.1, standardized difference 0.33). As the number of days increased between encounters from the 1 to < 14 days, there was a consistently lower likelihood of achieving BP control. Encounter intervals of ≥180 days were associated with the lowest likelihood of achieving BP control. These findings suggest that there may be an optimal number of encounters to benefit patients with hypertension.

Beta-blocker subtypes and risk of low birth weight in newborns

Beta‐blockers are one of the most commonly prescribed classes of antihypertensive medications during pregnancy. Previous studies reported an association between beta‐blocker exposure and intrauterine growth restriction. Whether some beta‐blocker subtypes may be associated with higher risk is not known. This is a retrospective cohort study of pregnant women exposed to beta‐blockers in the Kaiser Permanente Southern California Region between 2003 and 2014. Logistic regression models were used to evaluate association between exposure to different beta‐blocker agents and risk of low fetal birth weights. In a cohort of 379 238 singleton pregnancies, 4847 (1.3%) were exposed to beta‐blockers. The four most commonly prescribed beta‐blockers were labetalol (n = 3357), atenolol (n = 638), propranolol (n = 489), and metoprolol (n = 324). Mean birth weight and % low birth weight (<2500 g) were 2926 ± 841 g and 24.4% for labetalol, 3058 ± 748 g and 18.0% for atenolol, 3163 ± 702 g and 13.3% for metoprolol, 3286 ± 651 g and 7.6% for propranolol, and 3353 ± 554 g and 5.2% for non‐exposed controls. Exposure to atenolol and labetalol were associated with increased risks of infant born small for gestational age (SGA) (atenolol: adjusted OR 2.4, 95% CI: 1.7‐3.3; labetalol: adjusted OR 2.9, 95% CI: 2.6‐3.2). Risk of SGA associated with metoprolol or propranolol exposure was not significantly different from the non‐exposed group (metoprolol: adjusted OR 1.5, 95% CI: 0.9‐2.3; propranolol: adjusted OR 1.3, 95% CI: 0.9‐1.9). Association between beta‐blocker exposure and SGA does not appear to be a class effect. Variations in pharmacodynamics and confounding by indication may explain these findings.

Statin exposure during first trimester of pregnancy is associated with fetal ventricular septal defect

BACKGROUND A growing number of young women are exposed to statins during their first trimester of pregnancy. The goal of this study is to examine if first trimester statin exposure is associated with an increase in risk of fetal congenital cardiac anomalies. METHODS In a cohort of 379,238 pregnancies, we examined the risk of fetal congenital cardiac anomalies in association with maternal exposure to statin therapy during the first trimester of pregnancy using logistic regression models and propensity score matching methods. RESULTS 280 women were exposed to statins. Congenital cardiac anomalies were present in 14 (5.0%) of pregnancies exposed to statin and 5282 (1.4%) of non-exposed pregnancies. First-trimester statin exposure was associated with an increased risk of ventricular septal defect (adjusted odds ratio [OR] 3.3, 95% confidence interval [CI]l 1.8-6.0, p < 0.001). This association was confirmed in an analysis using a propensity score-matched cohort (OR 4.7, 95% CI 2.0-10.8, p < 0.001). CONCLUSIONS Exposure to statins during the first trimester of pregnancy is associated with fetal ventricular septal defect.

Comparison of Effects of Statin Use on Mortality in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction

Randomized trials showed no survival benefit with statin therapy in heart failure (HF) patients with reduced ejection fraction (HFrEF). Whether these results are generalizable to HF patients with preserved ejection fraction (HFpEF) or with mid-range ejection fraction is unclear. In a cohort of 13,440 patients with HF, 9,903 (73.7%) were treated with statins. The association between statin use and all-cause mortality was assessed with Cox proportional hazard regression models and survival time inverse probability weighting propensity scores analyses. Multivariable Poisson regression models with robust error variance were applied to estimate the rate ratios (RR) for hospitalization. The association between statin treatment and clinical outcomes differed by ejection fraction group. In patients with HFpEF, statin use was associated with reduced mortality (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.66 to 0.81, p <0.001; average treatment effect [ATE] 0.48, 95% CI 0.13 to 0.84, p = 0.007) and reduced all-cause hospitalization (RR 0.82, 95% CI 0.76 to 0.89, p <0.001). In contrast, in patients with HFrEF, no significant association was observed between statin use and mortality (HR 0.86, 95% CI 0.74 to 1.0, p = 0.054; ATE 0.41, 95% CI -0.09 to 0.93, p = 0.11) or hospitalization (RR 0.92, 95% CI 0.82 to 1.04, p = 0.17). Similarly, in patients with mid-range ejection fraction, there was no significant association with reduced mortality (HR 0.76, 95% CI 0.60 to 0.95, p = 0.02, ATE 0.3, 95% CI -0.84 to 1.43, p = 0.61) or hospitalization (RR 1.07, 95% CI 0.9 to 1.27, p = 0.44). In conclusion, statin use was associated with improved clinical outcomes in patients with HFpEF but not in patients with HFrEF or mid-range ejection fraction.

Competing Risks for Mortality in Patients With Asymptomatic Pancreatic Cystic Neoplasms: Implications for Clinical Management

Objectives:Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. Current clinical practice guidelines emphasize management based on cyst-related features. We aimed to evaluate the impact of comorbidity on mortality in PCN patients via competing risk analysis.Methods:We analyzed a retrospective cohort of patients diagnosed between 2005–2010, with follow-up through 2015, for overall and cause-specific mortality. Comorbidities were classified by the Charlson comorbidity index. We used Cox proportional hazards regression to evaluate the independent effect of cyst features, age, gender, and comorbidities on cause-specific mortality. Subgroup analysis was performed to determine the cause-specific mortality based on four a priori clinical profiles—healthy patients with low- or high-risk cysts, and high-comorbidity patients with low- or high-risk cysts.Results:A total of 1,800 patients with PCNs comprised the study cohort (median follow-up 5.7 years). A total of 402 deaths (22.3%) occurred during the study period: 43 pancreatic cancer and 359 non-pancreatic cancer deaths. Compared to healthy patients without any high-risk cyst features (reference group), patients with high comorbidity as well as high-risk cyst features had an increased risk of overall mortality (Cox hazard ratio 6.30, 95% confidence interval (CI) 4.71, 8.42, P<0.01), pancreatic cancer mortality (subdistribution hazard ratio (SHR) 51.13, 95% CI 6.35, 411.29, P<0.01), as well as non-pancreatic cancer mortality (SHR 5.24, 95% CI 3.85, 7.12, P<0.01). Meanwhile, low-risk patients with a high-risk cyst were more likely to experience pancreatic cancer mortality (SHR 68.14, 95% CI 9.27, 501.01, P<0.01) rather than non-pancreatic cancer mortality (SHR 1.22, 95% CI 0.88, 1.71, P=0.23), compared to the reference group. Similarly, compared to the reference group, high-risk patients with a low-risk cyst were more likely to experience non-pancreatic cancer mortality (SHR 3.96, 95% CI 2.98, 5.26, P<0.01) rather than pancreatic cancer mortality (SHR 2.35, 95% CI 0.14, 38.82, P=0.55).Conclusions:Most of the deaths in the study were unrelated to pancreatic cancer. This has implications for clinical management. By applying patient-related factors in conjunction with cyst features, we defined commonly encountered patient profiles to help guide PCN clinical management.