Citations

Abstract Aim Women with gestational diabetes mellitus (GDM) display adverse lifetime cardiometabolic health. We examined whether early metformin in GDM could impact cardiometabolic risk factors postpartum. Methods EMERGE, a double-blind, placebo-controlled trial, randomized pregnancies 1:1 to placebo or metformin at GDM diagnosis and followed participants from randomization until 12 ± 4 weeks postpartum. In total, 478 pregnancies were available for postpartum maternal assessment, 237 and 241 assigned to metformin and placebo respectively. Weight (kg), body mass index (BMI) (kg/m2), waist circumference (cm), and blood pressure (mmHg) were measured, infant feeding method documented, and blood specimens drawn for a 75-gram oral glucose tolerance test, fasting insulin, C-peptide, and lipid analysis. Results Despite similar weight and BMI at trial randomization, participants receiving metformin had significantly lower weight (79.5 ± 15.9 vs 82.6 ± 16.9 kg; P = .04) and BMI (29.3 [5.6] vs 30.5 [5.4]; P = .018) at the postpartum visit. However, no difference in weight change from randomization to 12 weeks postpartum was observed between metformin and placebo groups. Overall, 29% (n = 139) of the cohort met criteria for prediabetes or diabetes, with no positive impact with metformin. There were also no differences in measurements of insulin resistance, blood pressure, or lipids between groups. Conclusion Early metformin use in GDM did not impact important cardiometabolic parameters in the early postpartum period despite significant benefits in weight gain and insulin use in pregnancy.

Abstract Objective ANCA-negative granulomatosis with polyangiitis (GPA) remains a diagnosis of exclusion. Clinical differences between patients with ANCA-negative vs ANCA-positive GPA have not been analysed in sizable case-control studies, and the effects of ANCA-seroconversion from negative to positive are not well documented. Methods A single-centre, sex and age matched case-control study evaluated ANCA-negative vs ANCA-positive GPA from 1 January 1996 to 31 December 2015. Patients who experienced seroconversion were the subject of a case-crossover study. Clinical data and outcomes were retrieved from electronic medical records. Results ANCA-negative GPA was identified in 110 patients; 65% were female; median age was 55 (IQR 39–65) years at time of diagnosis. Disease severity was milder in ANCA-negative GPA (BVAS/WG = 2 vs 6, P < 0.001). Mucous membranous/eye manifestations were more frequent in ANCA-negative GPA. General symptoms, pulmonary and renal involvement were more frequent in ANCA-positive GPA. Patients with ANCA-positive GPA relapsed more over 60 months (21.8% vs. 9.1%, P = 0.009) compared with ANCA-negative GPA and had shorter time to event (P = 0.043). Patients with general manifestations, BMI > 30kg/m2 and necrotizing granulomatous inflammation were more likely to relapse. The 16 patients who seroconverted into ANCA-positive during follow-up had higher mean BVAS/WG at time of diagnosis (P < 0.001) and increased incidence of relapses (P = 0.004) after seroconversion. Necrotizing granulomatous inflammation on biopsy in ANCA-negative GPA patients was identified as a risk factor for subsequent seroconversion to ANCA-positivity. Conclusion Patients with ANCA-negative GPA have milder disease and a lower frequency of relapse than those with ANCA-positive GPA. ANCA appearance portended higher disease severity and an increased frequency of relapses.

Abstract Aims The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved. Methods and results We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular–pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660–0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656–0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference −0.072, 95% CI −0.123 to −0.020, p = 0.006, and −0.043, 95% CI −0.067 to −0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all). Conclusions Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.

Abstract Aims Women with congenital heart disease (CHD) are at risk of pregnancy-related adverse outcomes (PRAO). The purpose of this study was to assess temporal changes in cardiac structure and function (cardiac remodelling) during pregnancy, and the association with PRAO in women with CHD. Methods and results Retrospective study of pregnant women with CHD and serial echocardiograms (2003–2021). Cardiac structure and function were assessed at pre-specified time points: prepregnancy, early pregnancy, late pregnancy, and postnatal period. PRAO was defined as the composite of maternal cardiovascular, obstetric, and neonatal complications. The study comprised 81 women with CHD (age, 29 ± 5 years). Compared to the baseline echocardiogram, there was a relative increase in right ventricular systolic pressure (RVSP) (relative change 13 ± 5%, P < 0.001, in early pregnancy; and 18 ± 5%, P < 0.001, in late pregnancy). There was a relative decrease in right ventricle free wall strain (RVFWS) (relative change −11 ± 3%, P < 0.001, in late pregnancy; and −11 ± 4%, P = 0.003, in postnatal period), and a relative decrease in RVFWS/RVSP (relative change, −10 ± 5%, P = 0.02 in early pregnancy, −26 ± 7%, P < 0.001, in late pregnancy, and −14 ± 5%, P < 0.001, in postnatal period). Baseline right ventricular to pulmonary arterial (RV–PA) coupling, and temporal change in RV–PA coupling were associated with PRAO, after adjustment for maternal age and severity of cardiovascular disease. Conclusion Women with CHD had a temporal decrease in RV systolic function and RV–PA coupling, and these changes were associated with PRAO. Further studies are required to delineate the aetiology of deterioration in RV–PA coupling during pregnancy, and the long-term implications of right heart dysfunction observed in the postnatal period.

Abstract Hypertensive emergencies cause substantial morbidity and mortality, particularly when acute organ injury is present. Careful and effective strategies to reduce blood pressure and diminish the effects of pressure-mediated injury are essential. While the selection of specific antihypertensive medications varies little across different forms of hypertensive emergencies, the intensity of blood pressure reduction to the target pressure differs substantially. Treatment hinges on balancing the positive effects of lowering blood pressure with the potential for negative effects of organ hypoperfusion in patients with altered autoregulatory mechanisms. When patients do not have acute organ injury in addition to severe hypertension, they benefit from a conservative, outpatient approach to blood pressure management. In all cases, long term control of blood pressure is paramount to prevent recurrent hypertensive emergencies and improve overall prognosis. This review discusses the current evidence and guidelines on the evaluation and management of hypertensive emergency.

Objective Compare the effectiveness of palatoplasty and pharyngoplasty procedures at resolving hypernasality in patients with 22q11.2 deletion syndrome (22q). Design Retrospective cohort study. Setting Metropolitan children's hospital. Patients Fourteen patients with 22q presenting for management of velopharyngeal insufficiency. Interventions Palatoplasty or pharyngoplasty procedure. Main Outcome Measure Resolution of hypernasality 12 months postoperatively. Results Both procedure groups had a mean preoperative velopharyngeal gap of 6.2 mm during phonation. No patient who underwent palatoplasty achieved resolution of hypernasality; 1/7 patients had worse hypernasality, 4/7 had no change, and 2/7 had improved hypernasality. In contrast, hypernasality was resolved in 6/7 patients in the pharyngoplasty group, which was significantly ( P = .03) higher than the palatoplasty group. Conclusions In patients with 22q, palatoplasty procedures may be less effective than pharyngoplasty procedures at resolving hypernasality. This may be due to underlying anatomic or physiologic differences, such as increased pharyngeal depth and hypodynamic muscles.