Blinded, randomized trial of sonographer versus AI cardiac function assessment.

Artificial intelligence (AI) has been developed for echocardiography1-3, although it has not yet been tested with blinding and randomization. Here we designed a blinded, randomized non-inferiority clinical trial (ClinicalTrials.gov ID: NCT05140642; no outside funding) of AI versus sonographer initial assessment of left ventricular ejection fraction (LVEF) to evaluate the impact of AI in the interpretation workflow. The primary end point was the change in the LVEF between initial AI or sonographer assessment and final cardiologist assessment, evaluated by the proportion of studies with substantial change (more than 5% change). From 3,769 echocardiographic studies screened, 274 studies were excluded owing to poor image quality. The proportion of studies substantially changed was 16.8% in the AI group and 27.2% in the sonographer group (difference of -10.4%, 95% confidence interval: -13.2% to -7.7%, P < 0.001 for non-inferiority, P < 0.001 for superiority). The mean absolute difference between final cardiologist assessment and independent previous cardiologist assessment was 6.29% in the AI group and 7.23% in the sonographer group (difference of -0.96%, 95% confidence interval: -1.34% to -0.54%, P < 0.001 for superiority). The AI-guided workflow saved time for both sonographers and cardiologists, and cardiologists were not able to distinguish between the initial assessments by AI versus the sonographer (blinding index of 0.088). For patients undergoing echocardiographic quantification of cardiac function, initial assessment of LVEF by AI was non-inferior to assessment by sonographers.

Body Mass Index, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk.

BACKGROUND: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. METHODS: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. RESULTS: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. CONCLUSIONS: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

Incident stroke in individuals with peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM), a form of heart failure with reduced ejection fraction (HFrEF) that occurs during the final month of pregnancy through the first 5 months postpartum, is associated with heightened risk for maternal morbidity and mortality. Stroke is a common complication of HFrEF but there is limited data on the incidence of stroke in PPCM. METHODS: Using statewide, nonfederal administrative data from 2000 to 2015, we analyzed age-adjusted risk of stroke within 3 years after PPCM-associated pregnancies. RESULTS: PPCM was associated with a greater than 4-fold increased risk of pregnancy-related stroke (aHR 4.7, 95% CI: 3.0-7.5). This risk was highest at the time of PPCM diagnosis but remained elevated in the first postpartum year. CONCLUSION: Our findings confirm the strong association between PPCM and stroke, with risk that persists throughout and after the peripartum period.

Sex Differences in Myocardial and Vascular Aging.

It is well known that cardiovascular disease manifests differently in women and men. The underlying causes of these differences during the aging lifespan are less well understood. Sex differences in cardiac and vascular phenotypes are seen in childhood and tend to track along distinct trajectories related to dimorphism in genetic factors as well as response to risk exposures and hormonal changes during the life course. These differences underlie sex-specific variation in cardiovascular events later in life, including myocardial infarction, heart failure, ischemic stroke, and peripheral vascular disease. With respect to cardiac phenotypes, females have intrinsically smaller body size-adjusted cardiac volumes and they tend to experience greater age-related wall thickening and myocardial stiffening with aging. With respect to vascular phenotypes, sexual dimorphism in both physiology and pathophysiology are also seen, including overt differences in blood pressure trajectories. The majority of sex differences in myocardial and vascular alterations that manifest with aging seem to follow relatively consistent trajectories from the very early to the very later stages of life. This review aims to synthesize recent cardiovascular aging-related research to highlight clinically relevant studies in diverse female and male populations that can inform approaches to improving the diagnosis, management, and prognosis of cardiovascular disease risks in the aging population at large.

Pregnancy Outcomes in Women Who Developed Elevated Blood Pressure and Stage I Hypertension after 20 Weeks Gestation.

OBJECTIVE: The American College of Obstetrics threshold for hypertension (≥140/90 mm Hg) differs from those of the American College of Cardiology (ACC) and the American Heart Association (AHA). It is unknown if ACC/AHA hypertension levels are associated with adverse pregnancy outcomes (APOs) after 20 weeks gestation. The purpose of this study is to analyze APOs in women with blood pressure (BP) in the elevated or stage 1 range after 20 weeks gestation. STUDY DESIGN: This was a secondary analysis of the nuMoM2b prospective cohort study of 10,038 nulliparous, singleton pregnancies between 2010 and 2014. BP was measured at three visits during the pregnancy using a standard protocol. Women without medical comorbidities, with normal BP by ACC/AHA guidelines (systolic BP [SBP] < 120 and diastolic BP [DBP] < 80 mm Hg) up to 22 weeks, were included. Exposure was BP between 22 and 29 weeks gestation: normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP: 120-129 and DBP < 80 mm Hg), and stage 1 (SBP: 130-139 or DBP: 80-89 mm Hg). The primary outcome was hypertensive disorder of pregnancy (HDP) at delivery. Secondary outcomes included fetal growth restriction (FGR), placental abruption, preterm delivery, and cesarean delivery. Multivariable-adjusted odds ratio (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: Of 4,460 patients that met inclusion criteria, 3,832 (85.9%) had BP in the normal range, 408 (9.1%) in elevated, and 220 (4.9%) in stage 1 range between 22 and 29 weeks. The likelihood of HDP was significantly higher in women with elevated BP (aOR 1.71, 95%CI: 1.18,2.48), and stage 1 BP (aOR: 2.79, 95%CI: 1.84,4.23) compared to normal BP (p < 0.001). Stage 1 BP had twice odds of FGR (aOR: 2.33, 95%CI: 1.22,4.47) and elevated BP had three times odds of placental abruption (aOR: 3.03; 95%CI: 1.24,7.39). CONCLUSION: Elevated or stage 1 BP >20 weeks of pregnancy are associated with HDP, FGR, and placental abruption. KEY POINTS: · Elevated and stage 1 BP increases risk for HDP.. · Elevated BP increases risk for placental abruption.. · Stage 1 BP increases risk for FGR..

Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study.

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2-1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5-3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

The 2017 American College of Cardiology and American Heart Association blood pressure categories in the second half of pregnancy-a systematic review of their association with adverse pregnancy outcomes.

OBJECTIVE: A relationship between the 2017 American College of Cardiology and American Heart Association blood pressure thresholds and adverse pregnancy outcomes has been reported, but few studies have explored the diagnostic test properties of these cutoffs when used within pregnancy. DATA SOURCES: Electronic databases were searched (2017-2021) for measurements of blood pressure in pregnancy at >20 weeks, classified according to the 2017 American College of Cardiology and American Heart Association criteria, and their relationship with pregnancy outcomes. Blood pressure was categorized as "normal" (systolic blood pressure of <120 mm Hg and diastolic blood pressure of <80 mm Hg), "elevated blood pressure" (systolic blood pressure of 120-129 mm Hg and diastolic blood pressure of <80 mm Hg), "stage 1 hypertension" (systolic blood pressure of 130-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg), and "stage 2 hypertension" (systolic blood pressure of ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg). STUDY ELIGIBILITY CRITERIA: Studies recording blood pressure at or above 20 weeks gestation were included. METHODS: Meta-analyses were used to investigate the strength of the association between blood pressure cutoffs and adverse outcomes, and the diagnostic test properties were calculated accounting for gestation. RESULTS: There were 12 included studies. The American College of Cardiology or American Heart Association blood pressure categories were determined from peak blood pressures at any point from 20 weeks of gestation and at specific gestational ages (20-27, 28-32, or 33-36 weeks of gestation), as available. A higher (vs normal) blood pressure category was consistently associated with adverse outcomes. The strength of association between blood pressure categories and adverse outcomes was the greatest with "stage 2 hypertension" (blood pressure of ≥140/90 mm Hg). The results were similar when peak blood pressure was reported either at any time from 20 weeks of gestation or within gestational age groups (as above). No blood pressure category was useful as a diagnostic "rule-out test" for adverse outcomes, as all negative likelihood ratios were ≥0.2. Only "stage 2 hypertension" was useful as a "rule in-test," with positive likelihood ratios of ≥5.0, for maximum blood pressure at >20 weeks of gestation for preeclampsia and blood pressure within any gestational age groups for preeclampsia, eclampsia, stroke, maternal death, and stillbirth. CONCLUSION: From 20 weeks of gestation, blood pressure thresholds of 140 mm Hg (systolic) and 90 mm Hg (diastolic) were useful in identifying women at increased risk of adverse pregnancy outcomes, irrespective of the specific gestational age at blood pressure measurement. Lowering the blood pressure threshold for abnormal blood pressure at >20 weeks of gestation would not assist clinicians in identifying women at heightened maternal or perinatal risk. No American College of Cardiology or American Heart Association blood pressure threshold can provide reassurance that women are unlikely to develop adverse outcomes.

Hypertension Across a Woman's Life Cycle.

PURPOSE OF REVIEW: We reviewed the effects of hypertension and the means to prevent and treat it across the spectrum of a woman's lifespan and identified gaps in sex-specific mechanisms contributing to hypertension in women that need to be addressed. RECENT FINDINGS: Hypertension continues to be an important public health problem for women across all life stages from adolescence through pregnancy, menopause, and older age. There remain racial, ethnic, and socioeconomic differences in hypertension rates not only overall but also between the sexes. Blood pressure cutoffs during pregnancy have not been updated to reflect the 2017 ACC/AHA changes due to a lack of data. Additionally, the mechanisms behind hypertension development in menopause, including sex hormones and genetic factors, are not well understood. In the setting of increasing inactivity and obesity, along with an aging population, hypertension rates are increasing in women. Screening and management of hypertension throughout a women's lifespan are necessary to reduce the burden of cardiovascular disease, and further research to understand sex-specific hypertension mechanisms is needed.

Hypertension in Women Across the Lifespan.

PURPOSE OF REVIEW: We will highlight the biological processes across a women's lifespan from young adulthood through menopause and beyond that impact blood pressure and summarize women's representation in hypertension clinical trials. RECENT FINDINGS: Throughout their lifetime, women potentially undergo several unique sex-specific changes that may impact their risk of developing hypertension. Blood pressure diagnostic criteria for pregnant women remains 140/90 mmHg and has not been updated for concordance with the 2017 ACC/AHA guideline due to a lack of data. Although on a population level, women develop hypertension at later ages than men, new data shows women's BP starts to increase as early as the third decade. Understanding how age and sex both contribute to hypertension in elderly women is crucial to identify optimal blood pressure and treatment targets. Effective screening, monitoring, and treatment of hypertension throughout a women's lifespan are necessary to reduce CVD risk. We highlight several gaps in the literature pertaining to understanding sex-specific hypertension mechanisms.

Similarity-based health risk prediction using Domain Fusion and electronic health records data.

Electronic Health Record (EHR) data represents a valuable resource for individualized prospective prediction of health conditions. Statistical methods have been developed to measure patient similarity using EHR data, mostly using clinical attributes. Only a handful of recent methods have combined clinical analytics with other forms of similarity analytics, and no unified framework exists yet to measure comprehensive patient similarity. Here, we developed a generic framework named Patient similarity based on Domain Fusion (PsDF). PsDF performs patient similarity assessment on each available domain data separately, and then integrate the affinity information over various domains into a comprehensive similarity metric. We used the integrated patient similarity to support outcome prediction by assigning a risk score to each patient. With extensive simulations, we demonstrated that PsDF outperformed existing risk prediction methods including a random forest classifier, a regression-based model, and a naïve similarity method, especially when heterogeneous signals exist across different domains. Using PsDF and EHR data extracted from the data warehouse of Columbia University Irving Medical Center, we developed two different clinical prediction tools for two different clinical outcomes: incident cases of end stage kidney disease (ESKD) and severe aortic stenosis (AS) requiring valve replacement. We demonstrated that our new prediction method is scalable to large datasets, robust to random missingness, and generalizable to diverse clinical outcomes.

Receipt of Proton-Pump Inhibitors during Pregnancy and Risk for Preeclampsia.

OBJECTIVE: This study aimed to determine whether receiving a proton-pump inhibitor (PPI) prescription during pregnancy was associated with decreased risk for preeclampsia. STUDY DESIGN: The Truven Health MarketScan database was used to determine whether receiving a PPI prescription was associated with risk for preeclampsia. Risk for preeclampsia was evaluated based on the presence or absence of receiving a PPI prescription (1) any time during pregnancy, and 2) individually during the 1st, 2nd, and 3rd trimesters. In addition to evaluating risk for all preeclampsia, severe preeclampsia and preterm severe preeclampsia were evaluated. Adjusted models including risk factors such as chronic hypertension, maternal age, multiple gestation, and diabetes were performed with adjusted risk ratios (aRR) with 95% confidence intervals [CIs] as measures of effect. RESULTS: A total of 2,755,885 women were included in the analysis of whom 69,249 were prescribed a PPI during pregnancy (2.5%). In adjusted models, receiving a PPI prescription anytime during pregnancy (aRR 1.28, 95% CI 1.24-1.32), the 1st trimester (aRR 1.12, 95% CI 1.04-1.22), the 2nd trimester (aRR 1.20, 95% CI 1.15-1.26), and the 3rd trimester (aRR 1.41, 95% CI 1.35-1.47) were all associated with increased risk for preeclampsia. Risk for severe preeclampsia was also significantly increased with receiving a PPI prescription anytime during pregnancy (aRR 1.21, 95% CI 1.15-1.27), during the 2nd trimester (aRR 1.14, 95% CI 1.06-1.23), and during the 3rd trimester (aRR 1.33, 95% CI 1.24-1.43), but not the first trimester (aRR 1.04, 95% CI 0.92-1.19). Evaluating the risk for preterm severe preeclampsia, adjusted risk was significantly increased with receiving a PPI prescription in the second trimester (aRR 1.35, 95% CI 1.21-1.52) but not the first trimester (aRR 1.06, 95% CI 0.86-1.32). CONCLUSION: In this analysis of payer data, receiving a PPI prescription during pregnancy was not associated with decreased risk for preeclampsia. Further empiric research is required to determine whether an effect may be present. KEY POINTS: · Proton pump inhibitors were not associated with decreased risk for preeclampsia.. · Proton pump inhibitors were not associated with decreased risk for severe preterm preeclampsia.. · Proton pump inhibitors are commonly prescribed during pregnancy..

Associations Between Sleep Disorders and Hypertensive Disorders of Pregnancy and Materno-fetal Consequences.

PURPOSE OF THE REVIEW: To review the data supporting the associations between sleep disorders and hypertensive disorders of pregnancy, their diagnosis, consequences, treatment, and potential mechanisms. RECENT FINDINGS: The prevalence of sleep-disordered breathing, insomnia, and restless legs syndrome increases as pregnancy progresses secondary to physiologic changes associated with pregnancy. Sleep-disordered breathing is strongly associated with the development of gestational hypertension and preeclampsia, both of which are associated with increased risk of perinatal complications. Diagnosing sleep disorders in pregnant presents added challenges, but polysomnography remains the gold standard for diagnosing sleep-disordered breathing in this group. Sleep disorders, and especially sleep-disordered breathing, are highly prevalent among pregnant women and associated with hypertensive disorders of pregnancy. Clinicians should be mindful of this association and endeavor to identify at-risk women for further evaluation.

Prevention, Diagnosis, and Management of Hypertensive Disorders of Pregnancy: a Comparison of International Guidelines.

PURPOSE OF REVIEW: Hypertensive disorders of pregnancy (HDP)-gestational hypertension, preeclampsia, and eclampsia-are a leading cause of adverse maternal and perinatal outcomes internationally. Prevention, timely diagnosis, and prompt management can reduce associated morbidity. The purpose of this review is to compare international guidelines pertaining to HDP. RECENT FINDINGS: Fourteen HDP guidelines were compared relative to guidelines for the United States (US) where the authors practice. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. Recommended dose and gestational age at initiation vary. Diagnoses of chronic hypertension, gestational hypertension, and preeclampsia in pregnant women are similar, although blood pressure (BP) thresholds for antihypertensive medication initiation and treatment targets vary due to the limitations in high-quality evidence. There are differences among international HDP guidelines related to dose and timing of aspirin initiation, thresholds for antihypertensive medication initiation, and BP targets. However, all guidelines acknowledge the significant morbidity associated with HDP and advocate for timely diagnosis and management to reduce associated morbidity and mortality. More research is needed to understand optimal BP thresholds at which to initiate antihypertensive medication regimens and BP targets in pregnancy.

Cases in Precision Medicine: A Personalized Approach to Stroke and Cardiovascular Risk Assessment in Women.

Cardiovascular disease is the leading cause of death among women in the United States, and stroke is third. This article uses a case scenario to examine female sex-specific cardiovascular risk factors across the lifespan and describes a precision medicine-based approach to risk factor modification and primary prevention. It also presents recent updates to the role of genetic testing and polygenic risk scores for the prediction of stroke and cardiovascular disease.

Weight History and Subclinical Myocardial Damage.

BACKGROUND: Excess weight is associated with subclinical myocardial damage, as reflected by high-sensitivity cardiac troponin T (hs-cTnT) concentrations, which portends high heart failure risk. However, the association between weight history and myocardial damage is unknown. METHODS: We evaluated 9062 Atherosclerosis Risk in Communities (ARIC) visit 4 (1996-1999) participants with a body mass index (BMI) ≥ 18.5 kg/m2 and no previous cardiovascular disease. We cross-tabulated visit 4 ("current") BMI categories of normal weight, overweight, and obese with those at visit 1 (1987-1989) and with BMI categories calculated from self-reported weight at age 25 years. Duration of obesity was calculated in years. A cumulative weight measure of "excess BMI-years" was also calculated [product of mean BMI (centered at 25 kg/m2) over all ARIC time points × follow-up duration]. We used logistic regression to estimate associations of weight history metrics with increased hs-cTnT (≥14 ng/L) at visit 4. RESULTS: Overall, 623 individuals (7%) had increased hs-cTnT at visit 4. Within each current BMI category, previous excess weight was associated with increased hs-cTnT, with the strongest associations for those with past and current obesity [odds ratio (OR), 3.85; 95% CI, 2.51-5.90 for obesity at age 25 years and visit 4]. Each 10-year longer obesity duration was associated with increased hs-cTnT (OR, 1.26; 95% CI, 1.17-1.35). Each 100 higher excess BMI-years was also progressively associated with increased hs-cTnT (OR, 1.21; 95% CI, 1.14-1.27). CONCLUSIONS: Previous obesity and greater cumulative weight from young adulthood increase the likelihood of myocardial damage, indicating long-term toxic effects of adiposity on the myocardium and the need for weight maintenance strategies targeting the entire life span.

Out of Office Blood Pressure Measurement in Pregnancy and the Postpartum Period.

PURPOSE: Hypertensive disorders of pregnancy are increasing in prevalence and associated with significant maternal and perinatal morbidity and mortality. RECENT FINDINGS: Increased emphasis has been placed recently on the use of out-of-office (i.e., home and ambulatory) blood pressure (BP) monitoring to diagnose and manage hypertension in the general population. Current guidelines offer limited recommendations on the use of out-of-office BP monitoring during pregnancy and postpartum. This review will discuss the recent literature on BP measurement outside of the office and its use for screening, diagnosis, and treatment in pregnancy and postpartum, and will illuminate areas for future research.