Markers of Cardiovascular Risk Associated with Pregnancy.

PURPOSE OF REVIEW: The purpose of the review is to summarize the unique cardiovascular disease (CVD) risk factors encountered during pregnancy and to provide the reader with a framework for acquiring a comprehensive obstetric history during the cardiovascular (CV) assessment of women. RECENT FINDINGS: Individuals with a history of pregnancies complicated by hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), preterm delivery, low birth weight, and fetal growth restriction during pregnancy are at a higher risk of developing short- and long-term CV complications compared to those without adverse pregnancy outcomes (APOs). Women with a history of APOs can be at increased risk of CVD even after achieving normoglycemia and normal blood pressure control postpartum. Risk assessment and stratification in women must account for these APOs as recommended by the 2019 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the primary prevention of CVD. Early recognition, monitoring, and treatment of APOs are key to limiting CVD complications late in maternal life. Recognition of APOs as female-specific cardiovascular risk factors is critical for risk stratification for women and birthing persons. Further research is needed to understand the complex interplay between genetics, environmental, behavioral, and maternal vascular health, and the association between APOs and CVD risk.

Pregnancy Associated Heart Failure With Preserved Ejection Fraction: Risk Factors and Maternal Morbidity.

BACKGROUND: Cardiovascular conditions are leading contributors to increasing maternal morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) results in the majority of HF admissions in women, yet its impact in pregnancy is unknown. We examined the prevalence rates, risk factors and adverse pregnancy outcomes in women with HFpEF during pregnancy-related hospitalizations in the United States. METHODS AND RESULTS: We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2002 through 2014 using the National Inpatient Sample. HFpEF cases were identified using the 428.3 International Classification of Diseases, 9th edition, Clinical Modification code. Weighting variables were used to provide national estimates, unconditional survey logistic regression to generate odds ratios and 95% confidence intervals (CI) representing adjusted associations with adverse pregnancy outcomes and Joinpoint regression to estimate temporal trends. Among 58,732,977 hospitalizations, there were 3840 HFpEF cases, an overall rate of 7 cases per 100,000 pregnancy-related hospitalizations; 56% occurred postpartum, 27% during delivery, and 17% antepartum. The temporal trend for hospitalization increased throughout the timeframe by 19.4% (95% CI 13.9-25.1). HFpEF hospitalizations were more common for Black, older, or poor women. Risk factors included hypertension (chronic hypertension and hypertensive disorders of pregnancy), anemia, obesity, diabetes, renal disease and coronary atherosclerosis; all known risk factors for HFpEF. Women with HFpEF were 2.61-6.47 times more likely to experience adverse pregnancy outcomes. CONCLUSIONS: The pregnancy-related HFpEF hospitalization prevalence has increased and is associated with adverse pregnancy outcomes. Risk factors resemble those outside pregnancy, emphasizing the need for screening and monitoring women with risk factors during pregnancy for HFpEF.

Cardiomyopathies in Pregnancy: Etiologies and Management Strategies.

The cardiomyopathies are a diverse group of disorders characterized by structural abnormalities of heart muscle, many of which have a genetic component. They are associated with substantial morbidity and mortality in pregnancy. We review the distinct forms of cardiomyopathy (dilated, hypertrophic, and functional) which can be seen during pregnancy, discuss complications associated with each distinct group such as heart failure, arrhythmias, and transmission to offspring, and address management strategies for stable and unstable patients.

Maternal Obesity Affects Cardiac Remodeling and Recovery in Women with Peripartum Cardiomyopathy.

OBJECTIVE: To examine the association between maternal obesity on left ventricular (LV) size and recovery in women with peripartum cardiomyopathy (PPCM). STUDY DESIGN: This was a prospective analysis of 100 women enrolled within 13 weeks of PPCM diagnosis and followed for a year in the Investigation of Pregnancy Associated Cardiomyopathy study. Adiposity was defined by standard body mass index (BMI) definitions for under/normal weight, overweight, and obesity. Demographic, clinical, and biomarker variables were compared across weight categories. OUTCOMES: LV end-diastolic diameter (LVEDD) and ejection fraction were measured at entry, 6, and 12 months postpartum. Multivariable regression models examined the relationship between adiposity, LV size, and leptin levels with cardiac recovery at 6 and 12 months postpartum. RESULTS: Obese and nonobese women had similar LV dysfunction at entry. Obese women had greater LV size and less LV recovery at 6 and 12 months postpartum. BMI was positively associated with leptin and ventricular diameter. Greater BMI at entry remained associated with less ventricular recovery at 6 months (p = 0.02) in adjusted race-stratified models. LVEDD at entry predicted lower ejection fraction at 6 months (p < 0.001) and similarly at 12 months. CONCLUSION: Obese women with PPCM had greater cardiac remodeling, higher leptin levels, and diminished cardiac recovery.

Dicarbonyl stress and glyoxalase enzyme system regulation in human skeletal muscle.

Skeletal muscle insulin resistance is a hallmark of Type 2 diabetes (T2DM) and may be exacerbated by protein modifications by methylglyoxal (MG), known as dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2 (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein expression, activity, and regulation remain largely unexplored in skeletal muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase enzyme system in the skeletal muscle of subjects with T2DM (age: 56 ± 5 yr.; BMI: 32 ± 2 kg/m2) compared with lean healthy control subjects (LHC; age: 27 ± 1 yr.; BMI: 22 ± 1 kg/m2). Skeletal muscle biopsies obtained from the vastus lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU·m-2·min-1)-euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress and lower GLO1 protein expression (-78.8%), which inversely correlated with BMI, percent body fat, and HOMA-IR, while positively correlating with clamp-derived glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%), which is a positive regulator of GLO1, while Keap1 protein expression, a negative regulator of GLO1, was elevated (207%). Additionally, insulin stimulation during the clamp had a differential effect on NRF2, Keap1, and MG-modified protein expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle insulin resistance. Whether these phenotypic differences contribute to the development of T2DM warrants further investigation.

Pheochromocytoma: Secondary Hypertension in Pregnancy.

Secondary hypertension can occur from a variety of renal and endocrine disorders. Pheochromocytoma, a rare catecholamine-secreting neuroendocrine tumor, is associated with adverse maternal and fetal outcomes in the absence of a timely diagnosis and a coordinated multidisciplinary approach. Clues to diagnosis include resistant hypertension or an adrenal mass on imaging.

Cardiovascular Disease in Hispanic Women: JACC Review Topic of the Week.

Cardiovascular disease affects 37% of Hispanic women and is the leading cause of death among Hispanic women in the United States. Hispanic women have a higher burden of cardiovascular risk factors, are disproportionally affected by social determinants of health, and face additional barriers related to immigration, such as discrimination, language proficiency, and acculturation. Despite this, Hispanic women show lower rates of cardiovascular disease and mortality compared with non-Hispanic White women. However, this "Hispanic paradox" is challenged by recent studies that account for the diversity in culture, race, genetic background, country of origin, and social determinants of health within Hispanic subpopulations. This review provides a comprehensive overview of the cardiovascular risk factors in Hispanic women, emphasizing the role of social determinants, and proposes a multipronged approach for equitable care.

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.

Ambulatory arrhythmia monitoring in pregnant patients with palpitations.

UNLABELLED: OBJECTIVE To assess the frequency of rhythm disturbances (RDs) obtained following placement of a Holter monitor or an event loop recorder (ERT) in patients referred to cardiologists. STUDY DESIGN: Ninety-six gravidas were referred to the cardiology clinic for palpitations, syncope, or dizziness and had Holter monitoring or ERT after a baseline electroencephalogram. Arrhythmias were classified by severity. RESULTS: Gestational age at referral was 22.6 weeks ± 8.3 days. Sixty-five patients had ERTs performed, and 19 had Holter monitors. Seventy-six percent had benign arrhythmias. In our ERT cohort, history of arrhythmias showed a fourfold increase in serious RD during gestation (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.1 to 20.3, p = 0.01); obesity (body mass index > 30) had a fourfold increased risk (OR 4.0, 95% CI 1.0 to 1, p = 0.03). Serious RD did not result in greater chance of cesarean delivery or induction of labor, or a newborn with arrhythmias. CONCLUSION: Most pregnant women with palpitations have benign arrhythmias. ERT appears to be a better method of diagnosis in pregnant women.

Sex Differences in Thoracic Aortic Disease and Dissection: JACC Review Topic of the Week.

Despite its higher prevalence among men, women with thoracic aortic aneurysm and dissection (TAAD) have lower rates of treatment and surgical intervention and often have worse outcomes. A growing number of women with TAAD also desire pregnancy, which can be associated with an increased risk of aortic complications. Understanding sex-specific differences in TAAD has the potential to improve care delivery, reduce disparities in treatment, and optimize outcomes for women with TAAD.

Feasibility and preliminary efficacy of acupuncture for angina in an underserved diverse population.

PURPOSE: Stable angina is ischemic chest pain on exertion or with emotional stress. Despite guideline-directed therapy, up to 30% of patients have suboptimal pain relief. The aims of this study were to: (1) determine the feasibility and acceptability of a randomized controlled trial (RCT) of acupuncture; and (2) evaluate preliminary efficacy of acupuncture with respect to reduction of pain and increased functional status and health-related quality of life (HRQoL). METHODS: Participants with stable angina for ⩾1 month received either a standardized acupuncture protocol, twice per week for 5 weeks, or an attention control protocol. Measures included the McGill Pain Questionnaire (average pain intensity (API), pain now) and the Seattle Angina Questionnaire-7 (functional status, symptoms, and HRQoL). Feasibility was defined as ⩾80% recruitment, ⩾75% retention following enrollment, and ⩾80% completion. Descriptive statistics and mixed-effects linear regression were used for analysis. RESULTS: The sample (n = 24) had a mean age of 59 ± 12 years, was predominantly female (63%), and represented minority groups (8% White, 52% Black, 33% Hispanic, and 8% Other). Feasibility was supported by 79% retention and 89% completion rates. The recruitment rate (68%) was slightly lower than expected. Acceptability scores were 87.9% for the acupuncture group and 51.7% for the control group. Outcomes were significantly better for the acupuncture versus control groups (API, b = -2.1 (1.1), p = 0.047; functional status, b = 27.6 (7.2), p < 0.001; and HRQoL, b = 38.8 (11.9), p = 0.001). CONCLUSIONS AND IMPLICATIONS: Acupuncture was feasible and acceptable in our diverse sample. We were slightly under the recruitment target of 80%, but participants who started the study had a high likelihood of completing it. Acupuncture shows promise for stable angina, but its effectiveness needs to be confirmed by a larger, adequately powered RCT. TRIAL REGISTRATION NUMBER: NCT02914834 (ClinicalTrials.gov).

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.

Arrhythmias in Pregnancy.

Increasing maternal mortality and incidence of arrhythmias in pregnancy have been noted over the past 2 decades in the United States. Pregnancy is associated with a greater risk of arrhythmias, and patients with a history of arrhythmias are at significant risk of arrhythmia recurrence during pregnancy. The incidence of atrial fibrillation in pregnancy is rising. This review discusses the management of tachyarrhythmias and bradyarrhythmias in pregnancy, including management of cardiac arrest. Management of fetal arrhythmias are also reviewed. For patients without structural heart disease, ß-blocker therapy, especially propranolol and metoprolol, and antiarrhythmic drugs, such as flecainide and sotalol, can be safely used to treat tachyarrhythmias. As a last resort, catheter ablation with minimal fluoroscopy can be performed. Device implantation can be safely performed with minimal fluoroscopy and under echocardiographic or ultrasound guidance in patients with clear indications for devices during pregnancy. Because of rising maternal mortality in the United States, which is partly driven by increasing maternal age and comorbidities, a multidisciplinary and/or integrative approach to arrhythmia management from the prepartum to the postpartum period is needed.

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.

Cardiovascular Testing and Imaging in Pregnant Women.

Cardiovascular disease is a major contributor to maternal morbidity and mortality and frequently preventable. Women with known cardiovascular disease should undergo cardiac evaluation before pregnancy. Many women with pregnancy-associated cardiac complications are not previously known to have cardiac disease. Women at high risk or who have signs or symptoms suggestive of heart failure, angina, or arrhythmias should undergo prompt evaluation. This article describes various diagnostic imaging modalities that can be used in pregnancy, including indications, strengths, and limitations.

Team-Based Care of Women With Cardiovascular Disease From Pre-Conception Through Pregnancy and Postpartum: JACC Focus Seminar 1/5.

The specialty of cardio-obstetrics has emerged in response to the rising rates of maternal morbidity and mortality related to cardiovascular disease (CVD) during pregnancy. Women of childbearing age with or at risk for CVD should receive appropriate counseling regarding maternal and fetal risks of pregnancy, medical optimization, and contraception advice. A multidisciplinary cardio-obstetrics team should ensure appropriate monitoring during pregnancy, plan for labor and delivery, and ensure close follow-up during the postpartum period when CVD complications remain common. The hemodynamic changes throughout pregnancy and during labor and delivery should be considered with respect to the individual cardiac disease of the patient. The fourth trimester refers to the 12 weeks after delivery and is a key time to address contraception, mental health, cardiovascular risk factors, and identify any potential postpartum complications. Women with adverse pregnancy outcomes are at increased risk of long-term CVD and should receive appropriate education and longitudinal follow-up.

Socioeconomic Determinants of Health and Cardiovascular Outcomes in Women: JACC Review Topic of the Week.

Socioeconomic disparities in cardiovascular risk factors and outcomes exist among women, particularly those of minority racial or ethnic backgrounds. Barriers to optimal cardiovascular health begin early in life-with inadequate access to effective contraception, postpartum follow-up, and maternity leave-and result in excess rates of myocardial infarction, stroke, and cardiovascular death in at-risk populations. Contributing factors include reduced access to care, low levels of income and social support, and lack of diversity among cardiology clinicians and within clinical trials. These barriers can be mitigated by optimizing care access via policy change and improving physical access to care in women with geographic or transportation limitations. Addressing structural racism through policy change and bolstering structured community support systems will be key to reducing adverse cardiovascular outcomes among women of racial and ethnic minorities. Diversification of the cardiology workforce to more closely represent the patients we serve will be beneficial to all women.

Peripartum Cardiomyopathy: Management Strategies for Pregnancy Termination.

Some women have underlying cardiovascular disease that leads to increased morbidity and mortality with pregnancy. These women may choose to terminate a pregnancy rather than face this increased risk. The optimal approach for pregnancy termination in women with cardiomyopathy is not well defined. We present two women with peripartum cardiomyopathy, both modified World Health Organization (mWHO) class IV and with elevated Cardiac Disease in Pregnancy (CARPREG II) pregnancy risk stratification scores who are at the highest risk for pregnancy continuation. Both underwent induced abortion, although the procedure was performed in very different settings. These cases illustrate factors that influence the mode and setting of pregnancy termination performance.

Global Left Ventricular Strain at Presentation Is Associated with Subsequent Recovery in Patients with Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a serious complication of pregnancy associated with variable degrees of left ventricular (LV) recovery. The aim of this study was to test the hypothesis that global LV strain at presentation has prognostic value in patients with PPCM. METHODS: One hundred patients with PPCM aged 30 ± 6 years were enrolled in the multicenter Investigation in Pregnancy Associated Cardiomyopathy study along with 21 normal female control subjects. Speckle-tracking global longitudinal strain (GLS) and global circumferential strain (GCS) analysis was performed. The predefined primary combined outcome variable was death, transplantation, LV assist device implantation, or evidence of persistent LV dysfunction (LV ejection fraction [LVEF] < 50%) at 1 year. RESULTS: GLS measurement was feasible in 110 subjects: 89 of 90 patients with PPCM (99%) with echocardiographic data and all 21 control subjects. Of 84 patients (94%) with 1-year follow-up, 21 (25%) had unfavorable primary outcomes: four LV assist device placements, two deaths, and 15 patients with persistent LV dysfunction. GLS at presentation with a cutoff of 10.6% (absolute value) was specifically associated with the subsequent primary outcome with 75% sensitivity and 95% specificity. GCS at presentation with a cutoff of 10.1% was associated with the primary outcome with 78% sensitivity and 84% specificity. GLS and GCS remained significantly associated with outcomes after adjusting for LVEF (GLS odds ratio, 2.07; P < .001; GCS odds ratio, 1.37; P = .005). GLS was significantly additive to LVEF (C statistic = 0.76-0.91, net reclassification improvement = 1.32, P < .001). CONCLUSIONS: GLS and GCS in patients with PPCM at presentation were associated with subsequent clinical outcomes, including death, LV assist device implantation, and evidence of persistent LV dysfunction. Strain measures may add prognostic information over LVEF for risk stratification.