Prospective Observational Study of N-terminal Pro-Brain Natriuretic Peptide Levels in Obese and Nonobese Women during Pregnancy.

OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, varies by body mass index (BMI) outside of pregnancy. This study aimed to determine whether obesity affects NT-proBNP levels in pregnancy. STUDY DESIGN: This was a prospective observational study of healthy pregnant people in the third trimester (3TM) and postpartum (PP). Patients were excluded if they had significant medical comorbidities or if their fetuses had anomalies, growth restriction or aneuploidy. NT-proBNP was measured at 28 weeks (3TM), predelivery (PD), 1 to 2 days PP (immediate postpartum [IPP]), and 4 to 6 weeks PP (delayed postpartum [DPP]). LogNT-proBNP levels were analyzed using linear mixed effects models, including BMI < or ≥30, time, and time-by-BMI interactions. RESULTS: Fifty-five people (28 [51%] with BMI ≥ 30 and 27 [49%] with BMI < 30) were enrolled. A greater proportion of obese than nonobese subjects developed hypertensive disorders of pregnancy (50 vs. 15%, p = 0.010) and obese patients had higher systolic blood pressures at all time points (p < 0.05). NT-proBNP levels (median [interquartile range] in pg/mL) were 18 (6-28) versus 26 (17-48) at 3TM, 16 (3-38) versus 43 (21-60) at PD, 58 (20-102) versus 63 (38-155) at IPP, and 33 (27-56) versus 23 (8-42) at DPP for obese compared with nonobese patients. In linear mixed effects models, logNT-proBNP was lower in obese patients at 3TM (ß = -0.89 [95% confidence interval, CI: -1.51, -0.26]) and PD (ß = -1.05 [95% CI: -1.72, -0.38]). The logNT-proBNP trends over time differed by BMI category, with higher values in obese patients at both PP time points compared with the 3TM (IPP ß = 1.24 [95% CI: 0.75, 1.73]; DPP ß = 1.08 [95% CI: 0.52, 1.63]), but only IPP for nonobese patients (ß = 0.87 [95% CI: 0.36, 1.38]). CONCLUSION: Obese patients had lower NT-proBNP levels than nonobese patients during pregnancy but not PP. The prolonged PP elevation in NT-proBNP in obese patients suggests that their PP cardiac recovery may be more prolonged. KEY POINTS: · NT-proBNP levels are lower in obese than nonobese patients during pregnancy.. · Levels remain elevated in obese, but not nonobese, patients up to 4 to 6 weeks' postpartum.. · A lower threshold for concern regarding NT-proBNP levels may be needed in obese pregnant people..

Congenital and Acquired Valvular Heart Disease in Pregnancy.

PURPOSE OF REVIEW: The number of pregnancies complicated by valvular heart disease is increasing. This review describes the hemodynamic effects of clinically important valvular abnormalities during pregnancy and reviews current guideline-driven management strategies. RECENT FINDINGS: Valvular heart disease in women of childbearing age is most commonly caused by congenital abnormalities and rheumatic heart disease. Regurgitant lesions are well tolerated, while stenotic lesions are associated with a higher risk of pregnancy-related complications. Management of symptomatic disease during pregnancy is primarily medical, with percutaneous interventions considered for refractory symptoms. Most guidelines addressing the management of valvular heart disease during pregnancy are based on case reports and observational studies. Additional investigation is required to further advance the care of this growing patient population.

Maternal and Pregnancy Outcomes Following Heart Transplantation in the United States.

BACKGROUND: Improved survival following heart transplantation (HT) has led to more recipients contemplating pregnancy, but data on outcomes are limited. OBJECTIVES: The authors used a national data set to investigate and describe outcomes of pregnancies and deliveries in the United States in HT recipients. METHODS: Diagnosis and procedure codes from the 2010-2020 Nationwide Readmissions Database identified delivery hospitalizations, history of HT, comorbid conditions, and outcomes. The authors compared rates of severe maternal morbidity (SMM), nontransfusion SMM, cardiovascular SMM (cSMM), and preterm birth from delivery hospitalization between HT recipients and no-HT recipients. The authors evaluated readmission to 330 days postpartum. Logistic and proportional hazard regressions were performed, adjusting for age, socioeconomic and facility characteristics, and clinical comorbidities. RESULTS: Among 19,399,521 deliveries, 105 were HT recipients. Compared with no-HT, HT recipients were at higher risk for all SMM (24.8% vs 1.7%), nontransfusion SMM (20.8% vs 0.7%), cSMM (7.3% vs 0.12%), and preterm birth (43.3% vs 8.2%), all P < 0.001. In adjusted analyses, HT recipients had 16-fold greater odds of SMM, 28-fold greater odds of nontransfusion SMM, 38-fold greater odds of cSMM, and 7-fold greater odds of preterm birth. HT recipients had higher morbidity rates during delivery hospitalization and higher readmission rates within 1 year following delivery (26.9% vs 3.8%; adjusted HR: 6.03 [95% CI: 3.73-9.75]). CONCLUSIONS: Delivery with history of HT is associated with significantly increased rates of SMM, preterm birth, and hospital readmission. These results provide data regarding pregnancy outcomes for use when counseling patients with HT history who are considering pregnancy or who are pregnant.

Instituting a Curriculum for Cardio-Obstetrics Subspecialty Fellowship Training.

Maternal mortality is rising in the United States, and cardiovascular disease is the leading cause. Adverse pregnancy outcomes such as preeclampsia and gestational diabetes heighten the risk of cardiovascular complications during pregnancy and the peripartum period and are associated with long-term cardiovascular risks. The field of cardio-obstetrics is a subspecialty within adult cardiology that focuses on the management of women with or at high risk for heart disease who are considering pregnancy or have become pregnant. There is growing recognition of the need for more specialists with dedicated expertise in cardio-obstetrics to improve the cardiovascular care of this high-risk patient population. Current recommendations for cardiovascular fellowship training programs accredited by the Accreditation Council for Graduate Medical Education involve establishing core competency in the knowledge of managing heart disease in pregnancy. However, little granular detail is available of what such training should entail, which can lead to knowledge gaps. Additionally, dedicated advanced subspecialty training in this area is not commonly offered. Multidisciplinary collaborative teams have been shown to improve outcomes in cardiac patients during pregnancy, and cardiovascular fellows-in-training interested in cardio-obstetrics should have the opportunity to participate in and contribute to a pregnancy heart team. In this document, we describe a proposed specialized cardio-obstetrics training pathway that could serve to adequately prepare trainees to competently and comprehensively care for women with cardiovascular disease before, during, and after pregnancy.

Risk Factors and Outcomes Associated With Hypertensive Disorders of Pregnancy in Maternal Congenital Heart Disease.

Background: Among women with congenital heart disease (CHD), risk factors for hypertensive disorders of pregnancy (HDP) and the association of HDP with adverse outcomes are unknown. Objectives: The purpose of this study was to identify risk factors for HDP among women with and without CHD and to assess the association of HDP with adverse events. Methods: This retrospective cohort study included the first live birth for each woman who was pregnant in Alberta, Canada, between January 1, 2005, and December 31, 2018. The prevalence of HDP among women with and without CHD was compared. Multivariable models were used to determine the independent associations between maternal characteristics and HDP and to assess the strength of associations between HDP and CHD with adverse events. Results: Of the total birth events, 0.6% (N = 2,575) occurred in women with CHD. HDP were more common among women with CHD (11.2% vs 8.1%, P < 0.0001). Chronic hypertension and diabetes mellitus were strongly associated with HDP among women with CHD (adjusted odds ratio [aOR]: 4.56; 95% confidence interval [CI]: 2.95-7.03; and aOR: 3.33; 95% CI: 1.48-7.49, respectively). Coarctation of the aorta was the only CHD lesion independently associated with increased risk for HDP (aOR: 1.76; 95% CI: 1.02-3.02). HDP, as opposed to CHD, was more strongly associated with having a complicated delivery admission, preterm delivery, and small for gestational age infant. Conclusions: HDP were more common among women with CHD. The strongest risk factors for HDP among women with CHD were acquired. The presence of HDP, rather than CHD, was more strongly associated with certain adverse outcomes.

The utility of modified Butler-Leggett criteria for right ventricular hypertrophy in detection of clinically significant shunt ratio in ostium secundum-type atrial septal defect in adults.

BACKGROUND: This study was performed to test the hypothesis that there exists a correlation between the Butler-Leggett (BL) criterion for right ventricular hypertrophy on the electrocardiogram and the Qp/Qs shunt ratio in adults with ostium secundum atrial septal defects (ASDs). METHODS: Demographic, cardiac catheterization, ASD closure, and electrocardiographic data were acquired on 70 patients with secundum ASDs closed percutaneously. Simple linear regression and logistic regression models were created to test the hypothesis. RESULTS: The mean Qp/Qs ratio and BL criterion value were 1.61 +/- 0.46 and 0.11 +/- 0.41, respectively. The BL criterion values correlated with shunt ratios (r(2) = 0.11 and P = .004). A BL criterion value greater than 0 mV predicted a significant shunt ratio (Qp/Qs > or = 1.5) (odds ratio, 4.8; 95% confidence interval, 1.3, 18.1; P = or <.0001) with a sensitivity of 0.68 and specificity of 0.65. CONCLUSION: Our results indicate that there is limited utility of the BL criterion at detecting right ventricular volume overload, although a BL criterion value greater than 0 mV being used to identify patients with significant intracardiac shunts yielded a sensitivity of 0.68 and specificity of 0.65.

Right Ventricular Failure and Congenital Heart Disease.

Survivorship into adulthood of patients with congenital heart disease is due to improvements in prenatal detection, novel surgeries, and specialized adult congenital heart disease care. As patients survive further into adulthood, long-term complications of congenital and repaired physiology have been more clearly elucidated. The overall mortality of patients with adult congenital heart disease with heart failure is around 4%. Congenital malformations, palliations, residual defects, and resultant physiology impact the right ventricle. This relationship influences morbidity and mortality. For this discussion, focus on atrial septal defects, Ebstein anomaly, Tetralogy of Fallot, transposition of the great vessels, and single right ventricle physiology.

Impact of a Palliative Care Education Module in Patients With Heart Failure.

BACKGROUND: Heart failure (HF) impacts 6.2 million American adults. With no cure, therapies aim to prevent progression and manage symptoms. Inclusion of palliative care (PC) helps improve symptoms and quality of life. Heart failure guidelines recommend the inclusion of PC in HF therapy, but referrals are often delayed. OBJECTIVE: Introduce PC to patients with HF and examine the impact on PC consults, readmission, mortality, and intensive care unit (ICU) transfers. METHODS: Patients (n = 60) admitted with HF to an academic hospital were asked to view a PC educational module. A number of PC consults, re-admissions, mortality, and transfers to the ICU were compared among participants and those who declined. RESULTS: Nine patients in the intervention group (n = 30) requested a PC consult (P = .042) versus 2 in the usual care group (n = 30; P = .302). There was no statistically significant difference in readmissions, mortality, or ICU transfers between groups. CONCLUSIONS: Palliative care education increases the likelihood of PC utilization but in this short-term project was not found to statistically impact mortality, re-admissions, or transfers to higher levels of care.

Increased Risk of Aortic Dissection Associated With Pregnancy in Women With Turner Syndrome: A Systematic Review.

IMPORTANCE: Turner syndrome (TS) is one of the most common chromosomal abnormalities in women. The condition is characterized by gonadal dysgenesis and is associated with structural cardiac abnormalities. Assisted reproductive technology with oocyte donation may be successful but places women with TS at increased risk of aortic dissection and death. OBJECTIVE: To summarize all cases of aortic dissection associated with pregnancy in women with TS and provide guidance regarding the safety of pregnancy. EVIDENCE ACQUISITION: Systematic review of PubMed for reports of women with TS, aortic dissection, and pregnancy. RESULTS: There are 14 total reported cases of aortic dissection associated with pregnancy in women with TS. Ten of these cases occurred during pregnancy or in the first month postpartum. The majority of affected pregnancies resulted from oocyte donation, 2 of which were multiple gestations. Two women had a documented history of hypertension, and 3 pregnancies were complicated by preeclampsia. Bicuspid aortic valve and coarctation of the aorta were the most common associated cardiac anomalies. More than half of women had some degree of aortic dilatation. Two women had no identifiable risk factors. CONCLUSIONS AND RELEVANCE: Women with TS who desire pregnancy must be thoroughly counseled regarding the increased risk of aortic dissection during pregnancy and postpartum. Preconception consultation with maternal-fetal medicine, reproductive endocrinology, and cardiology is necessary along with a comprehensive physical evaluation. If women with TS choose to pursue pregnancy, they require rigorous cardiac monitoring each trimester during pregnancy and postpartum.

Evaluating the Impact of Interruptive Alerts within a Health System: Use, Response Time, and Cumulative Time Burden.

BACKGROUND: Health systems often employ interruptive alerts through the electronic health record to improve patient care. However, concerns of "alert fatigue" have been raised, highlighting the importance of understanding the time burden and impact of these alerts on providers. OBJECTIVES: Our main objective was to determine the total time providers spent on interruptive alerts in both inpatient and outpatient settings. Our secondary objectives were to analyze dwell time for individual alerts and examine both provider and alert-related factors associated with dwell time variance. METHODS: We retrospectively evaluated use and response to the 75 most common interruptive ("popup") alerts between June 1st, 2015 and November 1st, 2016 in a large academic health care system. Alert "dwell time" was calculated as the time between the alert appearing on a provider's screen until it was closed. The total number of alerts and dwell times per provider per month was calculated for inpatient and outpatient alerts and compared across alert type. RESULTS: The median number of alerts seen by a provider was 12 per month (IQR 4-34). Overall, 67% of inpatient and 39% of outpatient alerts were closed in under 3 seconds. Alerts related to patient safety and those requiring more than a single click to proceed had significantly longer median dwell times of 5.2 and 6.7 seconds, respectively. The median total monthly time spent by providers viewing alerts was 49 seconds on inpatient alerts and 28 seconds on outpatient alerts. CONCLUSION: Most alerts were closed in under 3 seconds and a provider's total time spent on alerts was less than 1 min/mo. Alert fatigue may lie in their interruptive and noncritical nature rather than time burden. Monitoring alert interaction time can function as a valuable metric to assess the impact of alerts on workflow and potentially identify routinely ignored alerts.

The Use of Implantable Cardioverter-defibrillators in the Prevention of Sudden Cardiac Death: A Focus on Congenital Heart Disease and Inherited Arrhythmia Syndromes.

Some congenital heart diseases (CHDs) and inherited arrhythmia syndromes are associated with an increased risk of sudden cardiac death (SCD). Appropriate selection criteria for implantable cardioverter-defibrillator (ICD) implantation in these patients are poorly defined due to a paucity of data available from randomized clinical trials, leading to current guidelines relying more on non-randomized studies and expert opinions to make their recommendations. This review describes available evidence-based risk stratification methods for identifying patients at risk for SCD, as well as current guideline-driven management strategies for the use of ICDs in patients with CHD and inherited arrhythmia syndromes.

Evaluation and Management of Maternal Congenital Heart Disease: A Review.

OBJECTIVE: Congenital heart defects represent the most common major congenital anomalies. The objective of this review was to define the most common forms of congenital heart disease (CHD) in pregnancy, outline preconception counseling, discuss the associated morbidity and mortality of each lesion, and review current recommendations for management of CHD in pregnancy. EVIDENCE ACQUISITION: A MEDLINE search of "congenital heart disease in pregnancy" and specific conditions in pregnancy including "ventricular septal defect," "atrial septal defect," "left outflow obstruction," "right outflow obstruction," "tetralogy of Fallot," and "transposition of the great vessels" was performed. RESULTS: The evidence included in the review contains 18 retrospective studies, 8 meta-analyses or systematic reviews or expert opinions, 5 case reports including surgical case reports, 2 prospective studies, and 2 clinical texts. CONCLUSIONS: Given advances in surgical and medical management, women with a history of congenital cardiac defects are more frequently reaching childbearing age and requiring obstetric care. Many women with CHD can have successful pregnancies, although there are a few conditions that confer significant maternal risk, and pregnancy may even be contraindicated. Appropriate care for women with CHD requires a knowledge of cardiac physiology in pregnancy, the common lesions of CHD, and coordinated care from cardiology and maternal-fetal medicine specialists.

Extra-cardiac manifestations of adult congenital heart disease.

Advancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations.

STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle.

It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. However, little is known about STIM1 in excitable cells, such as striated muscle, where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to show SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide insight into the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells.

Ablation of the secondary heart field leads to tetralogy of Fallot and pulmonary atresia.

Recent studies in chick and mouse embryos have identified a previously unrecognized secondary heart field (SHF), located in the ventral midline splanchnic mesenchyme, which provides additional myocardial cells to the outflow tract as the heart tube lengthens during cardiac looping. In order to further delineate the contribution of this secondary myocardium to outflow development, we labeled the right SHF of Hamburger-Hamilton (HH) stage 14 chick embryos via microinjection of DiI/rhodamine and followed the fluorescently labeled cells over a 96-h time period. These experiments confirmed the movement of the SHF into the outflow and its spiraling migration distally, with the right side of the SHF contributing to the left side of the outflow. In contrast, when the right SHF was labeled at HH18, the fluorescence was limited to the caudal wall of the lengthening aortic sac. We then injected a combination of DiI and neutral red dye, and ablated the SHF in HH14 or 18 chick embryos. Embryos were allowed to develop until day 9, and harvested for assessment of outflow alignment. Of the embryos ablated at HH14, 76% demonstrated cardiac defects including overriding aorta and pulmonary atresia, while none of the sham-operated controls were affected. In addition, the more severely affected embryos demonstrated coronary artery anomalies. The embryos ablated at HH18 also manifested coronary artery anomalies but maintained normal outflow alignment. Therefore, the myocardium added to the outflow by the SHF at earlier stages is required for the elongation and appropriate alignment of the outflow tract. However, at later stages, the SHF contributes to the smooth muscle component of the outflow vessels above the pulmonary and aortic valves which is important for the development of the coronary artery stems. This work suggests a role for the SHF in a subset of congenital heart defects that have overriding aorta and coronary artery anomalies, such as tetralogy of Fallot and double outlet right ventricle.

Secondary heart field contributes myocardium and smooth muscle to the arterial pole of the developing heart.

The arterial pole of the heart is the region where the ventricular myocardium continues as the vascular smooth muscle tunics of the aorta and pulmonary trunk. It has been shown that the arterial pole myocardium derives from the secondary heart field and the smooth muscle tunic of the aorta and pulmonary trunk derives from neural crest. However, this neural crest-derived smooth muscle does not extend to the arterial pole myocardium leaving a region at the base of the aorta and pulmonary trunk that is invested by vascular smooth muscle of unknown origin. Using tissue marking and vascular smooth muscle markers, we show that the secondary heart field, in addition to providing myocardium to the cardiac outflow tract, also generates prospective smooth muscle that forms the proximal walls of the aorta and pulmonary trunk. As a result, there are two seams in the arterial pole: first, the myocardial junction with secondary heart field-derived smooth muscle; second, the secondary heart field-derived smooth muscle with the neural crest-derived smooth muscle. Both of these seams are points where aortic dissection frequently occurs in Marfan's and other syndromes.