Faculty Bibliography

PURPOSE/OBJECTIVE:This study aimed to examine associations of bisphenol and phthalate exposure with arterial stiffness among women of reproductive age. METHODS:Participants include 637 adult women enrolled in the New York University Children's Health and Environment Study (NYU CHES), a prospective pregnancy cohort. The concentrations of eight bisphenols and 22 phthalate metabolites were quantified in up to three spot urine samples. Primary outcomes included brachial artery distensibility (BrachD) and carotid-femoral pulse wave velocity (cfPWV) as measures of peripheral and central arterial stiffness, respectively, along with blood pressure assessed at repeated study visits up to seven years from exposure measures. Associations between averaged, log2-transformed, creatinine-standardized chemical concentrations and subclinical vascular outcomes of interest were examined using linear mixed-effects models. RESULTS:In covariate-adjusted models, a doubling of bisphenol A was positively associated with BrachD (0.09%/mmHg, 95% confidence interval [CI] = 0.02, 0.16), a doubling of bisphenol S was negatively associated with mean arterial pressure (MAP) (-0.52 mmHg, 95% CI = -0.98, -0.05), a doubling of di(2-ethylhexyl) phthalate (DEHP) metabolites was negatively associated with diastolic blood pressure (DBP) (-0.81 mmHg, 95% CI = -1.38, -0.23) and MAP (-0.83 mmHg, 95% CI = -1.45, -0.21), and a doubling of antiandrogenic phthalate metabolites was associated with 0.62 mmHg lower DBP (95% CI = -1.22, -0.03) and 0.66 mmHg lower MAP (95% CI = -1.30, -0.02). CONCLUSION/CONCLUSIONS:These findings suggest that routine exposure to bisphenols and DEHP may be associated with vasorelaxation, potentially related to these chemicals' estrogenic and/or antiandrogenic effects.

INTRODUCTION/UNASSIGNED:Platelet hyperreactivity is linked to inflammation and cardiovascular risk in nonpregnant populations, but its relationship to placentally mediated pregnancy outcomes is undefined. We prospectively evaluated platelet hyperreactivity in pregnancy and subsequent ischemic placental disease (IPD), and examined aspirin's (ASA) effect on platelet activity by baseline platelet phenotype. METHODS/UNASSIGNED: RESULTS/UNASSIGNED:Of 66 pregnant participants recruited, 61 had first-trimester LTA; 20 (32.8%) had platelet hyperreactivity. Participants with hyperreactivity were more likely to develop IPD than those without (55% versus 24%, adjusted odds ratio [aOR] 3.77 (95% CI [1.05-13.53]), with consistent directionality across individual components despite low event frequencies. Participants with platelet hyperreactivity showed greater platelet aggregation to ADP, collagen, and low-dose AA. Platelet transcriptomic profiling distinguished participants with versus without platelet hyperreactivity and revealed differential expression of pathways related to platelet activity, energy metabolism, and immune regulation. Among 45 high-risk participants recommended ASA, those with hyperreactivity exhibited higher AA-induced aggregation (24% vs 12.5% platelet aggregation, p=0.01) despite similar serum TxB2 levels. CONCLUSION/UNASSIGNED:First-trimester platelet hyperreactivity was present in approximately one-third of participants and was independently associated with increased risk of IPD. Participants with platelet hyperreactivity demonstrated distinct transcriptomic signatures and greater platelet aggregation despite ASA use. Together, these findings support a contributory role for platelets in placental ischemic pathology and highlight the need to elucidate mechanisms and develop platelet-targeted preventive strategies.

BACKGROUND:Myocardial infarction with non-obstructive coronary arteries (MINOCA) has several underlying causes, including mimicking conditions in some cases. Imaging is recommended to identify MINOCA etiologies, but it remains unclear which patients are most likely to have abnormal findings. We characterized MINOCA mechanisms, analyzed predictors of imaging abnormalities and explored sex differences. METHODS:We enrolled patients with clinical diagnosis of MI in an international, prospective, diagnostic study at 28 sites in US, Canada and UK. After a women-only phase, we included both sexes. Individuals with ≥50% diameter stenosis or coronary dissection on angiography, or alternate causes for the clinical presentation, were excluded. Participants had multi-vessel coronary optical coherence tomography (OCT) during index coronary angiography and cardiac magnetic resonance imaging (CMR) within one week. Independent core laboratories interpreted imaging, blinded to other results. RESULTS:Among 754 patients enrolled, 389 had MINOCA and 336 with MINOCA underwent OCT (270 women and 66 men); CMR was completed in 284 (85%). An OCT-defined culprit lesion was identified in 45% (116/270 women [43% ] and 35/66 men [53%], p=0.18). CMR demonstrated an ischemic pattern in 114/284 (40%), similar by sex (96/225 women [43%] vs. 18/59 men [31%], p=0.12). A non-ischemic pattern was observed in 23% (23% of women, 25% of men, p=0.78). We identified a cause of the clinical presentation in 79% of patients with both tests completed: 59% had an ischemic cause of MINOCA and 20% had a non-ischemic mimicking condition. OCT alone found a MINOCA etiology in 151/336 (45%) and CMR alone in 180/284 (63%). Predictors of an OCT culprit lesion included age, abnormal angiogram, and number of vessels imaged, but 27% of normal angiograms harbored a culprit lesion. Predictors of abnormal CMR were peak troponin, shorter time to CMR, and non-Asian race, but CMR was abnormal in 40% when troponin was <4-fold above the upper reference limit. CONCLUSIONS:The combination of multi-vessel coronary OCT and CMR in patients with a clinical diagnosis of MINOCA confirmed MI in 59% and identified an alternate cause (MINOCA mimic) in 20%. Clinical factors had limited utility to predict imaging abnormalities. No sex differences in imaging results were detected.

BACKGROUND:Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6-15 % of MI patients. Cardiac magnetic resonance (CMR) imaging identifies MINOCA etiologies, but access may be limited. METHODS:We assessed associations between the index electrocardiogram (ECG) and CMR in MINOCA. Women with MI and < 50 % angiographic stenosis in all vessels were prospectively enrolled at 16 sites. CMR (median 6d from MI) was analyzed for late gadolinium enhancement (LGE), myocardial edema, and wall motion. We assessed ECGs for T-wave inversions (TWI), Q-waves (QW), ST-elevations (STE), ST-depressions (STD), and fragmented QRS complexes (fQRS). We calculated the DETERMINE score (# leads TWI + # fQRS +2*[# QW], excluding aVR, V1). RESULTS:Among 112 women with interpretable ECG, 81.3 % (91/112) had abnormal ECG; 50 % (56/112) had ≥1 TWI. CMR was abnormal in 74.1 % (83/112), with LGE in 49.1 % (55/112) and myocardial edema in 61.6 % (69/112). DETERMINE score ≥ 3 was associated with abnormal CMR (adjusted odds ratio [aOR] aOR 6.06 [1.89, 24.6], p = 0.002) and LGE (aOR 3.10 [1.26, 8.00], p = 0.013), but not edema (aOR 1.86 [0.80, 4.43], p = 0.152). TWI was also associated with abnormal CMR and LGE after adjustment (aOR 3.13 [1.08, 10.1], p = 0.036, aOR 3.23 [1.27, 8.63], p = 0.013, respectively), but not edema (aOR 1.26 [0.54, 2.96], p = 0.589). Specificity for abnormal CMR was 0.83 for DETERMINE score ≥ 3 and 0.75 for TWI. No other ECG findings were associated with CMR abnormality. CONCLUSION/CONCLUSIONS:DETERMINE score ≥ 3 and the presence of any TWI were associated with abnormal CMR and with LGE in MINOCA. Our findings demonstrate that the index ECG can provide insight on CMR findings but without sensitivity or specificity required to forgo the CMR. We reaffirm the central role of CMR in elucidating MINOCA pathophysiology.

BACKGROUND:Adverse pregnancy outcomes (APOs), hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm birth are associated with ischemic heart disease in later life. OBJECTIVES/OBJECTIVE:The authors aimed to study the features of premature myocardial infarction (MI) among women with and without prior APOs. METHODS:We performed a retrospective analysis of women with premature MI (<65 years of age) referred for left heart catheterization matched with a database of abstracted pregnancy data. We compared MI characteristics and epicardial coronary anatomy between women with and without APOs during their index pregnancy and evaluated time from delivery to MI. RESULTS:= 0.010). Women with and without APOs had similar MI features including rates of ST-segment elevation MI, obstructive and multi-vessel coronary artery disease, percutaneous coronary intervention, and shock. CONCLUSIONS:Among women with premature MIs, 39% had a history of an APO. Women with APO history presented sooner after pregnancy but had similar MI characteristics vs those without APOs. Pregnancy history may identify women who warrant early, aggressive cardiovascular disease prevention.

Background/UNASSIGNED:Women with infertility and heart disease (HD) are increasingly seeking assisted reproductive technology (ART). There is only one other study that examines the safety profile of ART in this population. This study aims to evaluate the cardiac, reproductive, and obstetric outcomes of ART in women with HD. Methods/UNASSIGNED:fertilization (IVF), oocyte cryopreservation (OC) or embryo banking (EB) with HD were included. Cases were matched 3:1 with age-, cycle type- and cycle start date- matched controls without HD. Outcomes included cardiovascular (CV), reproductive, and obstetric complications during or following ART. Results/UNASSIGNED:Twenty women with HD were included. 15 (75%) had congenital HD, 1 (5%) had valvular disease, 1 (5%) had acquired cardiomyopathy, and 3 (15%) had arrhythmias. 90% were New York Heart Association class I. 55% of HD cases were modified WHO (mWHO) risk classification 1-2, 40% were mWHO 2-3 or 3, 5% were mWHO 4. Cases underwent 25 IVF, 5 OC, and 5 EB cycles and were compared with 79 controls who underwent 174 cycles. No CV complications or deaths occurred amongst cases following ART or pregnancy. There was no difference in risk of ART or obstetric outcomes amongst cases versus controls. Conclusion/UNASSIGNED:For women with HD in this small, low -risk cohort, ART posed few risks that were similar in frequency to healthy controls.