Journal of Cardiovascular Development and Disease

Background: Aortic valve and root replacement (AVRR) is a standardised procedure to treat patients with aortic valve and root disease. In centres with a well-established aortic valve and root repair program (valve repairs and Ross operations), only patients with very complex conditions receive AVRR; this procedure uses a mechanical or biological composite valve graft (modified Bentall–de Bono procedure). The aim of the study was to evaluate the short- and long-term results after AVRR in a high-risk population with complex pathologies. Methods: Between 2005 and 2018, a total of 273 consecutive patients (mean age 64 ± 12.8 years; 23% female) received AVRR. The indication for surgery was an acute type A aortic dissection in 18%, infective endocarditis in 36% and other pathologies in 46% patients; 39% were redo procedures. The median EuroSCORE II was 11.65% (range 1.48–95.63%). Concomitant surgery was required in 157 patients (58%). Results: The follow-up extended to 5.2 years (range 0.1–15 years) and it was complete in 96% of the patients. The 30-day mortality was 17%. The overall estimated survival at 5 and 10 years was 65% ± 3% and 49% ± 4%, respectively. Univariate and multivariate logistic regression analyses revealed the following risk factors for survival: perioperative neurological dysfunction (OR 5.45), peripheral artery disease (OR 4.4) and re-exploration for bleeding (OR 3.37). Conclusions: AVRR can be performed with acceptable short- and long-term results in a sick patient population. The Bentall–De Bono procedure may be determined to be suitable for only elderly or high-risk patients. Any other patients should receive an AV repair or the Ross procedure in well-established centres. Full article

Pulmonary arterial hypertension (PAH), a female predominant disease, carries a high maternal and fetal mortality in pregnancy despite improved insight and the development of novel therapies. The high risk is attributed to the adaptive changes that take place to promote healthy fetal development during pregnancy, which can adversely affect the already compromised right ventricle in patients with PAH. While in the prior era emphasis was placed on termination of pregnancy, here we will illustrate through a multidisciplinary approach and meticulous planning at an expert center, these high-risk women can undergo successful childbirth. Full article

(1) Background: In pulmonary arterial hypertension (PAH), pregnancy is regarded a contraindication due to high maternal and fetal morbidity and mortality. We report our experience in the management of pregnancies in PAH. (2) Methods: retrospective observational study in a nationally accredited pulmonary hypertension (PH) center from 2013 to 2021. (3) Results: seven pregnancies in six women with PAH, ranging from low to high risk and 21 to 37 years old. Half had known pre-existing PAH before pregnancy. One had a multifetal gestation, and one was pregnant twice under our care. PH medical therapy and serial clinical assessment throughout pregnancy were implemented with focused attention on optimizing right heart function. Delivery was planned by a multidisciplinary team involving PH cardiology, maternal fetal medicine, and obstetric anesthesiology. Patients delivered between 31 and 40 weeks of gestation; five of the seven were via cesarean section. All received regional anesthesia and were monitored in the PH intermediate step-down unit after delivery until discharge. In all cases, delivery was without complications with excellent outcomes for the mother and child. (4) Conclusions: Multidisciplinary and tailored management of PAH in pregnancy, emphasizing optimized right heart function prior to delivery, can result in excellent clinical outcomes in a referral PH center. Full article

Background: The coronavirus disease 2019 (COVID-19) pandemic has restricted people’s activities and necessitated the discontinuation of cardiac rehabilitation (CR) programs for outpatients. In our hospital, CR for outpatients had to be discontinued for 3 months. We investigated the influence of this discontinuation of CR on physical activity, body composition, and dietary intake in cardiovascular outpatients. Method: Seventy-eight outpatients who restarted CR were investigated. We measured body composition, balance test, stage of locomotive syndrome, and food frequency questionnaire (FFQ) results at restart and 3 months later. We also investigated the results of examination that were obtained before discontinuation. Results: With regard to baseline characteristics, the percentage of male was 62.7% (n = 49), and average age and body mass index were 74.1 ± 8.5 years and 24.9 ± 7.0 kg/m², respectively. Stage of locomotive syndrome and the results of FFQ did not change significantly. The one-leg standing time with eyes open test significantly worsened at restart (p < 0.001) and significantly improved 3 months later (p = 0.007). With regard to body composition, all limb muscle masses were decreased at restart and decreased even further 3 months later. Conclusions: Discontinuation of CR influenced standing balance and limb muscle mass. While the restart of CR may improve a patient’s balance, more time is required for additional daily physical activities. The recent pandemic-related interruption of CR should inspire the development of alternatives that could ensure the continuity of CR in a future crisis. Full article

Background: Although degenerative aortic valve stenosis (DAS) is the most prevalent growth-up congestive heart valve disease, still little known about relationships between DAS severity, vascular stiffness (VS), echocardiographic parameters, and serum biomarkers in patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR). The objective of this study was to identify biomarkers associated with DAS severity, and those that are associated with cardiovascular death (CVD) and episodes of chronic heart failure (CHF) exacerbation. Methods: A total of 137 patients with initially moderate-to-severe DAS were prospectively evaluated for the relationship between DAS severity, baseline VS, and serum biomarkers (uPAR, GDF-15, Gal-3, IL-6Rα, ET-1, PCSK9, RANTES/CCL5, NT-proBNP, and hs-TnT), and were followed-up for 48 months. The prognostic significance of each variable for CVD and CHF risk was measured by hazard ratio of risk (HR), which was calculated by Cox’s proportional hazard model. Results: DAS severity showed correlations with IL-6Rα (r = 0.306, p < 0.001), uPAR (r = 0.184, p = 0.032), and NT-proBNP (r = −0.389, p < 0.001). Levels of ET-1 and Gal-3 were strongly correlated with VS parameters (r = 0.674, p < 0.001; r = 0.724, p < 0.001). Out of 137 patients, 20 were referred to TAVR, 88 to SAVR, and 29 to OMT. In TAVR patients, the highest levels of ET-1, Gal-3, and VS were found as compared to other patients. The highest incidence of CVD was observed in patients who underwent TAVR (35%), compared to SAVR (8%) and OMT (10.3%) (p = 0.004). In a multivariate analysis, ET-1 occurred predictive of CVD risk (HR 25.1, p = 0.047), while Gal-3 > 11.5 ng/mL increased the risk of CHF exacerbation episodes requiring hospital admission by 12%. Conclusions: Our study indicated that ET-1 and Gal-3 levels may be associated with the outcomes in patients with DAS. Full article

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term “elderly” corresponds to different ages in the literature, but it is defined by considerable comorbidity and heterogeneity. Cancer incidence, specifically colorectal cancer, is increased in older patients with IE and impacts its outcome. Diagnosis of IE in elderly patients is challenging due to the atypical presentation of the disease and the lower performance of imaging studies. Enterococcal etiology is more frequent than in younger patients. Antibiotic treatment should prioritize diminishing adverse effects and drug interactions while maintaining the best efficacy, as surgical treatment is less commonly performed in this population due to the high surgical risk. The global assessment of elderly patients with IE, with particular attention to frailty and geriatric profiles, should be performed by multidisciplinary teams to improve disease management in this population. Full article

We examined whether adding robot-supported balance exercises to cardiac rehabilitation improves the ability to balance in older adults with cardiovascular disease (CVD). We conducted a prospective study in 52 older adults who had been hospitalized for worsening CVD. Once weekly for four months, for a total of sixteen sessions as outpatients, the subjects used a Balance Exercise Assist Robot (BEAR) to perform balance exercises and an ergometer for aerobic exercises. Participants’ mean age was 76.9 ± 6.8 years (range, 65–95 years), and their mean brain natriuretic protein level was 164.0 ± 190.0 pg/mL. After the intervention, participants showed significant improvements in gait speed (before, 1.06 ± 0.33 m/s; after, 1.23 ± 0.30 m/s; p < 0.001), Short Physical Performance Battery score (before, 10.02 ± 2.25; after, 10.88 ± 1.79; p ˂ 0.001), timed up-and-go (before, 11.11 ± 5.07 s; after, 9.45 ± 3.45 s; p ˂ 0.001), and knee extension (before, 26.97 ± 11.78 kgf; after, 30.13 ± 13.04 kgf; p = 0.001). Cardiac rehabilitation including exercises using BEAR improved physical functioning and the ability to balance in older adults with CVD. Frail and prefrail patients improved, whereas robust ones did not change. Full article

Background: Literature suggests an association between shift work and cardiovascular disease (CVD). Limited evidence is available on how a cessation of shift work affects CVD risk factors. Aim: We investigated whether a five-month plant shutdown affected CVD risk factors in 30 industrial shift workers. Methods: We collected demographic data, self-reported data on physical activity (PA) and medical history by questionnaire. Pre- and post-plant shutdown, we measured blood pressure (BP), heart rate, lipids, glycosylated hemoglobin (HbA1c) and C-reactive protein (CRP). Additionally, we collected markers of inflammation, Matrix metalloproteinase-9 (MMP-9), Interleukin-6 (IL-6), Monocyte chemoattractant protein-1 (MCP-1), Tumor necrosis factor-alpha (TNF-α), P-selectin, Interleukin-1 beta (IL-1β), and Interleukin-23 (IL-23). We also examined arterial stiffness (central blood pressure, augmentation pressure, and pulse wave velocity) by means of SphygmoCor^® (AtCor Medical Pty Ltd., Sydney, Australia). We monitored sleep by actigraphy prior to and after plant shutdown, with additional registration of sleep quality and assessment of insomnia symptoms. Results: After five months of plant shutdown, we found that HbA1c increased by 1.9 mmol/mol, weight by 1 kg and MCP-1 by 27.3 pg/mL, all unexpectedly. The other markers of inflammation did not change during shutdown, but CRP decreased close to significant levels. There were no changes in lipids during follow-up. Pulse-wave velocity (PWV) was reduced from 8.1 m/s (SD = 1.5) to 7.6 m/s (SD = 1.5), p = 0.03. The workers reported fewer signs of insomnia after shutdown. Conclusions: Our findings suggest that a five-month cessation in shift work increases weight and HbA1c, but also improves insomnia symptoms and reverses arterial stiffening. Full article

Due to shortages of medical resources during the Coronavirus Disease 2019 (COVID-19) pandemic, an allocation algorithm for Transcatheter Aortic Valve Replacement (TAVR) was established. We investigated the impact on patient selection and procedural results. In total, 456 TAVR patients before (pre-COVID-19 group) and 456 TAVR patients after (COVID-19 group) the implementation of our allocation algorithm were compared. Concerning patient characteristics, the COVID-19 group revealed a higher rate of cardiac decompensations/cardiogenic shocks (10.5% vs. 1.3%; p < 0.001), severe angina pectoris (Canadian Cardiovascular Society (CCS) II, III and IV: 18.7% vs. 11.8%; p = 0.004), troponin elevation (>14 ng/L: 84.9% vs. 77%; p = 0.003) and reduced left ventricular ejection fraction (LVEF) (<45%: 18.9% vs. 12%; p = 0.006). Referring to procedural characteristics, more predilatations (46.3% vs. 35.1%; p = 0.001) and a longer procedural time (80.2 min (+/−29.4) vs. 66.9 min (+/−17.5); p < 0.001) were observed. The success rate was evenly high; no differences in safety parameters were reported. Examining the utilization of hospital resources, the COVID-19 group showed a shorter in-hospital stay (8.4 days (+/−5.9) vs. 9.5 days (+/−9.33); p = 0.041) and fewer TAVR patients were treated per month (39 (+/−4.55) vs. 46.11 (+/−7.57); p = 0.03). Our allocation algorithm supported prioritization of sicker patients with similar efficient and safe TAVR procedures. In-hospital stay could be shortened. Full article

Cardioneuroablation (CNA) is proposed as a promising therapy for patients with sinoatrial node dysfunction (SND) that is mediated by excessive vagal tone. However, a series of urgent questions about CNA remain unanswered. From December 2020 to March 2022, six patients with symptomatic SND who underwent CNA were summarized in this report. Sequential CNA targeting Ao-SVC GP, PMLGP, RAGP, and LSGP was performed in patients, guided by fractionated intracardiac electrograms and dynamically evaluated by extracardiac vagal stimulation (ECVS). The results showed that Ao-SVC GP ablation led to a significant increase in heart rate (HR) and the elimination of sinus arrest evoked by ECVS, while the vagal responses of atrial ventricular block were eliminated by the ablation of PMLGP and LSGP. Post-procedure HR increased up to 64–86% of the maximum HR of an atropine test at baseline. The median HR from Holter monitoring increased from 52.8 ± 2.1 bpm at baseline to 73.0 ± 10.4 bpm after the procedure (p = 0.012) and to 71.3 ± 10.1 bpm at the six-month follow-up (p = 0.011). Bradycardia-related symptoms disappeared in all patients at the six-month follow-up. This case series reveals the feasibility of using the ECVS-assisted sequential CNA technique and indicates the critical role of ECVS in dynamically evaluating the impact of sequential CNA on the vagal control of SAN and AVN. Full article

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the first human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the fourth post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19th century, but did not receive much recognition by embryologists. Full article

Background: Takotsubo syndrome (TTS) is a syndrome with ambiguous pathophysiology. Impaired kidney function (KF) seems to impact the outcome of patients with TTS. We hypothesized that KF worsens the outcome among TTS patients and furthermore, TTS patients with concomitant KF experience more adverse events compared to myocardial infarction (MI) patients with concomitant KF. Methods and Results: This retrospective single-center study comprised two groups (cohorts) of patients including patients with TTS and concomitant KF (n = 61, 27.1%) and patients with MI and concomitant KF (n = 164, 72.9%). The clinical outcomes were delineated as short-term outcomes defined as in-hospital adverse events during index hospitalization and long-term outcomes defined as adverse events over five-year clinical follow-ups. All-cause mortality, stroke, cardiopulmonary resuscitation (CPR), life-threatening arrhythmias, need for respiratory support, and cardiogenic shock with subsequent use of inotropic agents during index hospitalization were denoted as in-hospital adverse events. All-cause mortality, rehospitalization due to heart failure, stroke, thromboembolic events, and the recurrence of primary pathology (TTS and MI) were analyzed during five-year follow-ups after index hospitalization. A higher mortality rate was noted among TTS patients with KF compared to TTS without KF. In addition, in-hospital event rates in patients with TTS and concomitant KF compared to MI and concomitant KF were comparable with the exception of a higher rate of respiratory support in TTS patients. The mortality rate was significantly higher among patients with TTS and KF at 4 years (29.5% vs. 15.9%, p = 0.02) and 5 years (34.4% vs. 20.7%, p = 0.03) in comparison to patients with MI and concomitant KF. In contrast, the rate of re-hospitalization related to heart failure was higher at 30 days, and at one-, four-, and five-year follow-ups in patients suffering from MI and KF compared to TTS and concomitant KF. Additionally, the recurrence of MI after 4 and 5 years was higher than the recurrence of TTS (4.9% vs. 15.2%; 4.9% vs. 16.5%). There were no differences in life-threatening arrhythmias and stroke in both groups. Conclusions: Patients with TTS and concomitant KF have higher all-cause mortality when compared to MI and concomitant KF. The mechanisms responsible remain to be determined. Full article

Congenital heart disease (CHD) is a frequent occurrence, with a prevalence rate of almost 1% in the general population. However, the pathophysiology of the anomalous heart development is still unclear in most patients screened. A definitive genetic origin, be it single-point mutation or larger chromosomal disruptions, only explains about 35% of identified cases. The precisely choreographed embryology of the heart relies on timed activation of developmental molecular cascades, spatially and temporally regulated through epigenetic regulation: chromatin conformation, DNA priming through methylation patterns, and spatial accessibility to transcription factors. This multi-level regulatory network is eminently susceptible to outside disruption, resulting in faulty cardiac development. Similarly, the heart is unique in its dynamic development: growth is intrinsically related to mechanical stimulation, and disruption of the intrauterine environment will have a direct impact on fetal embryology. These two converging axes offer new areas of research to characterize the cardiac epigenetic regulation and identify points of fragility in order to counteract its teratogenic consequences. Full article

Sudden infant death syndrome (SIDS), the most common cause of infant death in developed countries, is attributed to diverse trigger factors. Malignant cardiac dysrhythmias are potentially treatable etiologies, and congenital long QT syndrome (LQTS) is the most common cardiac ionic channelopathy confronted. β-Blockers or class Ib agents are the drugs of choice for the control of arrhythmias, and an implantable cardioverter defibrillator (ICD) should be considered for secondary prevention in survivors of lethal cardiac death. We report the case of a 4-day old neonate, later genetically confirmed as LQT type 3 (LQT3), who survived a pulseless torsades de pointes (TdP) attack and was successfully treated with propranolol, mexiletine, and ICD implantation. Full article

Athlete ECG interpretation criteria have been developed and refined from research in athlete populations; however, current guidelines are based on available data primarily from Caucasian and Black athletes. This study aimed to assess the impact of ethnicity on ECG interpretation in athletes. A systematic review was conducted of the MEDLINE, EMBASE, Scopus, SPORTDiscus, and Web of Science databases, for papers that assessed athlete screening ECGs and compared findings on the basis of ethnicity. Fifty-one papers which compared ECGs from various ethnicities were included. Most studies assessed Black athletes against Caucasian athletes and found a greater prevalence of T-wave inversion (TWI) (2.6–22.8% vs. 0–5.0%) and anterior TWI (3.7–14.3% vs. 0.6–2.0%). Black athlete subgroups in Africa had TWI (20–40%) and anterior TWI (4.3–18.7%) at a higher prevalence than other Black athletes. Athletes who were defined as mixed-race, Asian, and Pacific Islander are potentially more like Black athletes than Caucasian athletes. Black ethnicity is known to have an impact on the accurate interpretation of athlete ECGs; however, there is nuance related to origin of both parents. Asian and Pacific Islander origin also may impact athlete ECG interpretation. Further research is required to assist in distinguishing abnormal and normal athlete ECGs in different ethnic populations. Full article

Purpose: The “FIDE Project” (Fitness Implantable DEvice) was organized by the Institute of Sports Medicine and Science and the World Society of Arrhythmias with the aim of demonstrating the usefulness of exercise training in improving functional capacity in patients with implantable cardiac devices. Materials and Methods: Thirty sedentary patients were selected for the project (25 males and 5 females), with a mean age of 73 ± 5 years (range 44–94 years). Twenty-five were implanted with a Pacemaker (PM) and five with an Implantable Cardioverter Defibrillator (ICD). Atrial fibrillation/atrial flutter was present in ten (34%) patients, post-ischemic dilated cardiomyopathy in five (17.2%), sick sinus syndrome in six (20,7%), complete atrium-ventricular block in six (20.7%), hypertrophic cardiomyopathy in one (3.4%) and recurrent syncope in one (3.4%). The baseline assessment comprised cardiovascular examination, resting and stress ECG, cardiopulmonary exercise testing (V ̇O2peak), strength assessment of different muscle groups, and a flexibility test. The same measurements were repeated after 15–20 consecutive training sessions, over a 2-month period. The exercise prescription was set to 70–80% of HRR (Heart rate reserve) and to 50–70% of 1RM (1-repetition maximum, muscular force). The training protocol consisted of two training sessions per week performed in our institute, 90 min for each (warm-up, aerobic phase, strength phase and stretching) and one or more at home autonomously. Results: The cardiopulmonary testing after the training period documents a significant improvement in V ̇O2peak (15 ± 4 mL/kg/min vs. 17 ± 4; p = 0.001) and in work load (87 ± 30 watts vs. 108 ± 37; p = 0.001). Additionally, strength capacity significantly increased after the cardiac rehabilitation program, (quadriceps: 21 ± 18 kg vs. 29 ± 16 kg, p = 0.00003). Flexibility tests show a positive trend, but without statistical significance (sit-and-reach test: −19 ± 11 cm vs. −15 ± 11.7 cm; back-scratch test: −19 ± 11.6 cm vs. −15 ± 10 cm; lateral flexibility right −44 ± 1.4 cm vs. −43 ± 9.5 cm; left −43 ± 5 vs. −45 ± 8.7 cm). Conclusion: A brief period of combined aerobic, strength and flexibility exercise training (FIDE project) proved to be effective and safe in improving functional capacity in patients with cardiac implantable devices. Full article

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training. Full article

Purpose: We assessed the application of appropriate use criteria of coronary computed tomography angiography (CCTA) in comparison to invasive coronary angiography results and revascularization rates in patients with coronary artery disease (CAD). Methods: 1305 patients referred to invasive coronary angiography (ICA) after CCTA were evaluated retrospectively. The primary indication for CCTA was assessed according to the consensus for intermediate-risk (15–85% pre-test probability) into appropriate (A), inappropriate (I), and uncertain while referring to published guidelines. Patients’ risk factors, angina, and heart failure symptoms (Canadian Cardiovascular Society classification (CCSC), New York Heart Association (NYHA); clinical data; and ICA results were gathered. Results: Of 1305 patients referred to CCTA prior to ICA, 496 (38.0%) were appropriate, 766 (56.9%) inappropriate, and 43 (3.3%) uncertain. Of 766 patients with inappropriate CCTA referrals, 370 (48.3%) were classified as “inappropriately low” (<15% pre-test probability) and 396 (51.7%) as “inappropriately high” (>85%) in regard to the recommended CCTA utilization. Sub-analysis of the adherence to the appropriate use criteria did not differ between the source of the referring physicians (intramural tertiary, private practice primary care, or external secondary care hospitals). Obstructive CAD with subsequent revascularization rates (total of 39.2%) did not differ significantly between the appropriate (38.3%), inappropriate (41.0%), or uncertain (23.3%) groups (p = 0.068). Conclusion: The total coronary revascularization rate after CCTA was 39.2% and not different among low, intermediate, and pre-test probability groups. These findings support the role of CCTA as an excellent gatekeeper in patients with suspected obstructive CAD even beyond pre-test probability calculation models. Full article

Diabetes mellitus (pregestational (PDM) and gestational (GDM)) is associated with adverse pregnancy outcomes (APOs). However, studies exploring the association of APOs with maternal glycemia among women without PDM/GDM are limited. We utilized data from 4119 women (307—PDM; 582—GDM; 3230—non-PDM/GDM) in the Boston Birth Cohort (1998–2016). Women in the non-PDM/GDM group were subdivided by tertiles of 1 h, 50 g oral glucose load test at 24–32 weeks: T1: 50–95 mg/dL (n = 1166), T2: 96–116 mg/dL (n = 1151), T3: 117–201 mg/dL (n = 913). Using multivariable logistic regression, we examined the association of maternal glycemia with APOs—preterm birth (PTB) and hypertensive disorders of pregnancy (HDP)—and adverse perinatal outcomes—high birth weight (HBW), cesarean section (CS), and sub-analyses by race-ethnicity. Compared to women in T1, women in T2 and T3 had a higher prevalence of pre-existing hypertension (T1: 2.8% vs. T2: 5.2% vs. T3: 6.3%) and obesity (T1: 13.3% vs. T2: 18.1% vs. T3: 22.9%). Women in T2 and T3 had higher odds of HBW (adjusted odds ratio aOR T2: 1.47 [1.01–2.19] T3: 1.68 [1.13–2.50]) compared to women in T1. Additionally, women in T2, compared to T1, had higher odds of HDP (aOR 1.44 [1.10–1.88]). Among non-Hispanic Black (NHB) women, those in T2 and T3 had higher odds of HDP compared to T1 (aOR T2 1.67 [1.13–2.51]; T3: 1.68 [1.07–2.62]). GDM and PDM were associated with higher odds of HBW, CS, PTB, and HDP, compared to women in T1. In this predominantly NHB and Hispanic cohort, moderate maternal glycemia without PDM/GDM was associated with higher odds of HBW and HDP, even more strongly among NHB women. If confirmed, a review of current guidelines of glucose screening and risk stratification in pregnancy may be warranted. Full article