Cardio-Obstetrics: A Focused Review.

PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of maternal mortality in the USA. All cardiovascular care providers should have a foundational knowledge on the management of pregnant individuals with heart disease. This focused review touches on several key cardio-obstetric themes. RECENT FINDINGS: Many individuals with cardiovascular disease can safely undergo pregnancy, but should have counseling preconception to optimize cardiac status. There are several cardiovascular conditions that are high risk for maternal mortality and morbidity. These individuals should be adequately counseled preconception and offered reliable birth control. The approach to a high-risk pregnant patient with cardiac disease is best managed by a multidisciplinary team to address potential maternal and fetal complications. Identification of at risk individuals can be estimated preconception with several risk scores. The development of risk scores to stratify and identify those at elevated risk during pregnancy is an area of continued research and development.

First Trimester Cardiac Biomarkers among Women with Peripartum Cardiomyopathy: Are There Early Clues to This Late-Pregnancy Phenomenon?

OBJECTIVE: Whether biomarkers may enable early identification of women who develop peripartum cardiomyopathy (PPCM) prior to disease onset remains a question of interest. STUDY DESIGN: A retrospective nested case-control study was conducted to determine whether first trimester N-terminal pro-B type natriuretic peptide (NT-proBNP) or high sensitivity cardiac troponin I (hs-cTnI) differed among women who developed PPCM versus unaffected pregnancies. Cases were matched to unaffected women by age, race, parity, and gestational age of sample (control A) and then further by blood pressure and pregnancy weight gain (control B). RESULTS: First trimester NT-proBNP concentrations were numerically higher among women who subsequently developed PPCM (116 pg/mL [83-177]) as compared with women in control A (56.1 pg/mL [38.7-118.7], p = 0.3) or control B (37.6 [23.3 - 53.8], p <0.05). A higher proportion of women who subsequently developed PPCM (50%) had detectable levels of hs-cTnI as compared with control A (0%, p = 0.03) or control B (18.8%, p = 0.52). Among both cases and controls, hs-cTnI values were low and often below the limit of detection. CONCLUSION: There were differences in first trimester NT-proBNP and hs-cTnI concentrations between women who subsequently developed PPCM and those who did not, raising the possibility the early pregnancy subclinical myocardial dysfunction may be associated with this late-pregnancy disease. KEY POINTS: · First trimester NT-proBNP is numerically higher among women who subsequently develop PPCM.. · First trimester hs-cTnI was nominally higher among women who developed PPCM versus those who did not.. · A significant proportion of normal pregnant women have undetectable hs-cTnI..

Menopausal age and left ventricular remodeling by cardiac magnetic resonance imaging among 14,550 women.

The present study included 14,550 postmenopausal female participants in the UK Biobank who completed cardiac magnetic resonance imaging. Earlier age at menopause was significantly and independently associated with smaller left ventricular end-diastolic volume and smaller stroke volume, a pattern suggesting acceleration of previously described age-related left ventricular remodeling. These findings may have implications for understanding mechanisms of heart failure, specifically heart failure with preserved ejection fraction, among women with early menopause.

Association of Premature Natural and Surgical Menopause With Incident Cardiovascular Disease.

Importance: Recent guidelines endorse using history of menopause before age 40 years to refine atherosclerotic cardiovascular disease risk assessments among middle-aged women. Robust data on cardiovascular disease risk in this population are lacking. Objective: To examine the development of cardiovascular diseases and cardiovascular risk factors in women with natural and surgical menopause before age 40 years. Design, Setting, and Participants: Cohort study (UK Biobank), with adult residents of the United Kingdom recruited between 2006 and 2010. Of women who were 40 to 69 years old and postmenopausal at study enrollment, 144 260 were eligible for inclusion. Follow-up occurred through August 2016. Exposures: Natural premature menopause (menopause before age 40 without oophorectomy) and surgical premature menopause (bilateral oophorectomy before age 40). Postmenopausal women without premature menopause served as the reference group. Main Outcomes and Measures: The primary outcome was a composite of incident coronary artery disease, heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation, ischemic stroke, peripheral artery disease, and venous thromboembolism. Secondary outcomes included individual components of the primary outcome, incident hypertension, hyperlipidemia, and type 2 diabetes. Results: Of 144 260 postmenopausal women included (mean [SD] age at enrollment, 59.9 [5.4] years), 4904 (3.4%) had natural premature menopause and 644 (0.4%) had surgical premature menopause. Participants were followed up for a median of 7 years (interquartile range, 6.3-7.7). The primary outcome occurred in 5415 women (3.9%) with no premature menopause (incidence, 5.70/1000 woman-years), 292 women (6.0%) with natural premature menopause (incidence, 8.78/1000 woman-years) (difference vs no premature menopause, +3.08/1000 woman-years [95% CI, 2.06-4.10]; P < .001), and 49 women (7.6%) with surgical premature menopause (incidence, 11.27/1000 woman-years) (difference vs no premature menopause, +5.57/1000 woman-years [95% CI, 2.41-8.73]; P < .001). For the primary outcome, natural and surgical premature menopause were associated with hazard ratios of 1.36 (95% CI, 1.19-1.56; P < .001) and 1.87 (95% CI, 1.36-2.58; P < .001), respectively, after adjustment for conventional cardiovascular disease risk factors and use of menopausal hormone therapy. Conclusions and Relevance: Natural and surgical premature menopause (before age 40 years) were associated with a small but statistically significant increased risk for a composite of cardiovascular diseases among postmenopausal women. Further research is needed to understand the mechanisms underlying these associations.

Aspirin Use in Women: Current Perspectives and Future Directions.

PURPOSE OF REVIEW: This review examines the recent literature on the use of low-dose aspirin (LDA) for primary and secondary prevention of cardiovascular disease in women, use of LDA for pre-eclampsia prevention in pregnancy, and the underutilization of aspirin therapy in women as compared to men. RECENT FINDINGS: While men and women should not differ with respect to aspirin use for secondary prevention, its role in primary prevention remains unclear for both sexes, with particular uncertainty in women. Reflective of this are conflicting recommendations in current guidelines for primary prevention and thus investigations of primary prevention aspirin use are ongoing and will play an important role in elucidating its efficacy. While there is significant heterogeneity in studies to date of LDA for pre-eclampsia prevention, based on recent meta-analyses suggesting promising results, guidelines now recommend initiation in high risk women after the 12th week of gestation. Finally, studies consistently reveal that aspirin therapy is underutilized in women as compared to men, suggesting a need to better educate physicians and the general public about its use in women. Further research is needed to better elucidate the role of aspirin in women for primary prevention of cardiovascular disease and for pre-eclampsia in high risk pregnant women. In addition, further investigation into the factors that lead to the current underutilization of aspirin in women are required in order to ensure that patients of both sexes are optimally treated, with the goal of improving cardiovascular outcomes in all patients.

Bicoastal Spontaneous Coronary Artery Dissection: A Therapeutic Dilemma.

Due to the potential for severe maternal morbidity and even mortality, pregnancy-associated spontaneous coronary artery dissection (P-SCAD) often presents as a clinical conundrum. While current recommendations encourage coronary interventions when medically indicated even during pregnancy, the hesitation still understandably exists. Meanwhile, given the rarity of the condition, the guidelines for management are still based on expert consensus. We present a case of P-SCAD in a 38-year-old woman with initial presentation at 28 weeks' gestation and recurrence at 9 days postpartum. A unique complication of this case is its transcontinental nature: the initial event occurred while the patient was on vacation across the country from her home. Questions arose not only with regard to her immediate management and care but also when she would be able to travel and how her complex care would be continued cross-country. This case raised important questions regarding the antepartum management of acute coronary syndrome (ACS). It also highlights the importance of multidisciplinary care, especially with a cardio-obstetrics team, in the management of P-SCAD and emphasizes the role for universal screening for cardiac diseases in pregnancy.

Recommendations for the Management of High-Risk Cardiac Delivery: ACC Cardiovascular Disease in Women Committee Panel.

Maternal mortality is a major public health crisis in the United States. Cardiovascular disease (CVD) is a leading cause of maternal mortality and morbidity. Labor and delivery is a vulnerable time for pregnant individuals with CVD but there is significant heterogeneity in the management of labor and delivery in high-risk patients due in part to paucity of high-quality randomized data. The authors have convened a multidisciplinary panel of cardio-obstetrics experts including cardiologists, obstetricians and maternal fetal medicine physicians, critical care physicians, and anesthesiologists to provide a practical approach to the management of labor and delivery in high-risk individuals with CVD. This expert panel will review key elements of management from mode, timing, and location of delivery to use of invasive monitoring, cardiac devices, and mechanical circulatory support.

Maternal Cardiovascular Health Post-Dobbs.

Maternal Cardiovascular Health Post-DobbsPregnancy is associated with increasing morbidity and mortality in the United States. In the post-Dobbs era, many pregnant patients at highest risk no longer have access to abortion, which has been a crucial component of standard medical care.

Coronary Microvascular Function Following Severe Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (ß, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (ß, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (ß, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.

Coronary Microvascular Function Following Severe Preeclampsia.

Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating pro- and anti-angiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. Methods: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography (PET) within 4 weeks of delivery. A control group of pre-menopausal, non-postpartum women was also included. Myocardial flow reserve (MFR), myocardial blood flow (MBF), and coronary vascular resistance (CVR) were compared across groups. Soluble fms-like tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) were measured at imaging. Results: The primary cohort included 19 women with severe preeclampsia (imaged at a mean 16.0 days postpartum), 5 with normotensive pregnancy (mean 14.4 days postpartum), and 13 non-postpartum female controls. Preeclampsia was associated with lower MFR (ß=-0.67 [95% CI -1.21 to -0.13]; P=0.016), lower stress MBF (ß=-0.68 [95% CI, -1.07 to -0.29] mL/min/g; P=0.001), and higher stress CVR (ß=+12.4 [95% CI 6.0 to 18.7] mmHg/mL/min/g; P=0.001) vs. non-postpartum controls. MFR and CVR after normotensive pregnancy were intermediate between preeclamptic and non-postpartum groups. Following preeclampsia, MFR was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest MBF (r=0.71; P<0.001), independent of hemodynamics. Conclusions: In this exploratory study, we observed reduced coronary microvascular function in the early postpartum period following severe preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves the coronary microcirculation. Further research is needed to establish interventions to mitigate risk of preeclampsia-associated cardiovascular disease.

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.

Importance: Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease. Objective: To identify proteins in the circulation associated with HDPs. Design, Setting, and Participants: Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023. Exposures: Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs). Main Outcomes and Measures: Gestational hypertension and preeclampsia. Results: Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins. Conclusions and Relevance: Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.

Infertility and Risk of Heart Failure in the Women's Health Initiative.

BACKGROUND: There is growing recognition that reproductive factors are associated with increased risk of future cardiovascular disease. Infertility has been less well studied, although emerging data support its association with increased risk of cardiovascular disease. Whether infertility is associated with future risk of heart failure (HF) is not known. OBJECTIVES: This study sought to examine the development of HF and HF subtypes in women with and without history of infertility. METHODS: We followed postmenopausal women from the Women's Health Initiative prospectively for the development of HF. Infertility was self-reported at study baseline. Multivariable cause-specific Cox models were used to evaluate the association of infertility with incident overall HF and HF subtypes (heart failure with preserved ejection fraction [HFpEF]: left ventricular ejection fraction of ≥50% vs heart failure with reduced ejection fraction [HFrEF]: left ventricular ejection fraction of <50%]). RESULTS: Among 38,528 postmenopausal women (mean age: 63 ± 7 years), 5,399 (14%) participants reported a history of infertility. Over a median follow-up of 15 years, 2,373 developed incident HF, including 807 with HFrEF and 1,133 with HFpEF. Infertility was independently associated with future risk of overall HF (HR: 1.16; 95% CI: 1.04-1.30; P = 0.006). Notably, when examining HF subtypes, infertility was associated with future risk of HFpEF (HR: 1.27; 95% CI: 1.09-1.48; P = 0.002) but not HFrEF (HR: 0.97; 95% CI: 0.80-1.18). CONCLUSIONS: Infertility was significantly associated with incident HF. This was driven by increased risk of HFpEF, but not HFrEF, and appeared independent of traditional cardiovascular risk factors and other infertility-related conditions. Future research should investigate mechanisms that underlie the link between infertility and HFpEF.

Evaluation and management of blood lipids through a woman's life cycle.

There are currently no sex-specific guidelines for evaluation and management of blood lipids. While previous guidelines acknowledge sex-specific risk enhancing factors for lipid management in women for CVD prevention, this review focuses on how lipids are impacted during normal hormonal changes throughout a woman's life cycle- during adolescence, pre-pregnancy, pregnancy, pre- and perimenopause, menopause, and at older ages. In this review, the authors focus on management of primary prevention of CVD by examining sex-specific cardiovascular risk factors at each stage and pay special attention to statin use, statin side effects and non-statin therapies. Women need to understand their personalized cholesterol goals and ally with their clinicians to ensure successful management. Additionally, we highlight the biases that exist when treating dyslipidemia in women and the special care clinicians should take to ensure appropriate and aggressive therapies are made available to female patients. Finally, the authors recommend future research should focus on increasing enrollment of women in lipid trials. This is of paramount importance in discovering sex-specific difference in lipid management.

Cardiovascular Complications of Pregnancy-Associated COVID-19 Infections.

Cardiovascular complications are frequently present in coronavirus-2019 (COVID-19) infection. These include microvascular and macrovascular thrombotic complications such as arterial and venous thromboembolism, myocardial injury or inflammation resulting in infarction, heart failure, and arrhythmias. Data suggest increased risk of adverse outcomes in pregnant compared with nonpregnant women of reproductive age with COVID-19 infection, including need for intensive care unit admission, mechanical ventilation, and extracorporeal membrane oxygenation utilization. Current statements addressing COVID-19-associated cardiac complications do not include pregnancy complications that may mimic COVID-19 complications such as peripartum cardiomyopathy, spontaneous coronary artery dissection, and preeclampsia. Unique to pregnancy, COVID-19 complications can result in preterm delivery and modify management of the pregnancy. Moreover, pregnancy has often been an exclusion criterion for enrollment in research studies. In this review, we summarize what is known about pregnancy-associated COVID-19 cardiovascular complications.

Pregnancy Considerations in the Multidisciplinary Care of Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a vasoconstrictive disease of the distal pulmonary vasculature resulting in adverse right heart remodeling. Pregnancy in PAH patients is associated with high maternal morbidity and mortality as well as neonatal and fetal complications. Pregnancy-associated changes in the cardiovascular, pulmonary, hormonal, and thrombotic systems challenge the complex PAH physiology. Due to the high risks, patients with PAH are currently counseled against pregnancy based on international consensus guidelines, but there are promising signs of improving outcomes, particularly for patients with mild disease. For patients who become pregnant, multidisciplinary care at a PAH specialist center is needed for peripartum monitoring, medication management, delivery, postpartum care, and complication management. Patients with PAH also require disease-specific counseling on contraception and breastfeeding. In this review, we detail the considerations for reproductive planning, pregnancy, and delivery for the multidisciplinary care of a patient with PAH.

The Utilization and Interpretation of Cardiac Biomarkers During Pregnancy: JACC: Advances Expert Panel.

Cardiac biomarkers are widely used in the nonpregnant population when acute cardiovascular (CV) pathology is suspected; however, the behavior of these biomarkers in the context of pregnancy is less well understood. Pregnant individuals often have symptoms that mimic those of cardiac dysfunction, and complications of pregnancy may include CV disease. This paper will summarize our current knowledge on the use of cardiac biomarkers in pregnancy and provide suggestions on how to use these tools in clinical practice based on the available evidence. Natriuretic peptides and troponin should not be measured routinely in uncomplicated pregnancy, where values should remain low as in the nonpregnant population. In the context of pre-existing or suspected CV disease, these biomarkers retain their negative predictive value. Elevations of both natriuretic peptides and troponin may occur without clear clinical significance in the immediate postpartum period. Elevations of these markers should always prompt further investigation into possible CV pathology.

Pregnancy outcome in thoracic aortic disease data from the Registry Of Pregnancy And Cardiac disease.

BACKGROUND: Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease is commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered a high risk period in women with underlying aortopathy. METHODS: The ESC EORP Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective global registry that enrolled 5739 women with pre-existing cardiac disease. With this analysis, we aim to study the maternal and fetal outcome of pregnancy in women with thoracic aortic disease. RESULTS: Thoracic aortic disease was reported in 189 women (3.3%). Half of them were patients with Marfan syndrome (MFS), 26% had a BAV, 8% Turner syndrome, 2% vascular Ehlers-Danlos syndrome and 11% had no underlying genetic defect or associated congenital heart defect. Aortic dilatation was reported in 58% of patients and 6% had a history of aortic dissection. Four patients, of whom three were patients with MFS, had an acute aortic dissection (three type A and one type B aortic dissection) without maternal or fetal mortality. No complications occurred in women with a history of aortic dissection. There was no significant difference in median fetal birth weight if treated with a beta-blocker or not (2960 g (2358-3390 g) vs 3270 g (2750-3570 g), p value 0.25). CONCLUSION: This ancillary analysis provides the largest prospective data review on pregnancy risk for patients with thoracic aortic disease. Overall pregnancy outcomes in women with thoracic aortic disease followed according to current guidelines are good.