Evaluation of the effect of sodium zirconium cyclosilicate on arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with hyperkalaemia: protocol for the multicentre, randomised, controlled DIALIZE-Outcomes study.

INTRODUCTION: Patients with kidney failure receiving chronic haemodialysis have elevated risk of arrhythmias potentially increasing the likelihood of sudden cardiac death, stroke and hospitalisation. The DIALIZE study (NCT03303521) demonstrated that sodium zirconium cyclosilicate (SZC) was an efficacious and well-tolerated treatment for predialysis hyperkalaemia in patients undergoing haemodialysis. The DIALIZE-Outcomes study evaluates the effect of SZC on sudden cardiac death and arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with recurrent hyperkalaemia. METHODS AND ANALYSIS: International, multicentre, randomised, double-blind, placebo-controlled study conducted at 357 study sites across 25 countries. Adults (≥18 years) receiving chronic haemodialysis three times per week with recurrent predialysis serum potassium (K+) ≥5.5 mmol/L post long interdialytic interval (LIDI) are eligible. Patients (~2800) will be randomised 1:1 to SZC or placebo, starting at 5 g orally once daily on non-dialysis days and titrated weekly in 5 g increments (maximum 15 g) to target predialysis serum K+ 4.0-5.0 mmol/L post LIDI. The primary objective is to evaluate efficacy of SZC versus placebo in reducing occurrence of the primary composite endpoint of sudden cardiac death, stroke or arrhythmia-related hospitalisation, intervention or emergency department visit. Secondary endpoints include efficacy of SZC versus placebo in maintaining normokalaemia (serum K+ 4.0-5.5 mmol/L post LIDI) at the 12-month visit, preventing severe hyperkalaemia (serum K+ ≥6.5 mmol/L post LIDI) at the 12-month visit and reducing the incidence of individual cardiovascular outcomes. Safety of SZC will be evaluated. The study is event driven, with participants remaining in the study until 770 primary endpoint events have occurred. Average time in the study is expected to be ~25 months. ETHICS AND DISSEMINATION: Approval was obtained from the relevant institutional review board/independent ethics committee from each participating site (approving bodies in supplementary information). The results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: EudraCT 2020-005561-14 and clinicaltrials.gov identifier NCT04847232.

Indeterminate Prenatal Ultrasounds and Maternal Anxiety: A Prospective Cohort Study.

INTRODUCTION: Prenatal ultrasounds often yield indeterminate (incomplete or minor abnormality) findings with limited clinical utility. We evaluate impact of indeterminate findings on maternal anxiety. METHODS: A single-U.S.-center prospective cohort study administered the Perinatal Anxiety Screening Scale (PASS; control mean = 13.4; > 20 denotes clinically significant anxiety) before and after prenatal ultrasounds in February-May 2017. Ultrasound reports were coded as: normal; indeterminate; or major abnormality. Primary outcome was anxiety after indeterminate vs. normal ultrasounds. Secondary outcomes included anxiety change from pre-to-post-ultrasound and relative to women's characteristics. Linear regression adjusted for confounders. RESULTS: Of 286 ultrasounds, 51.0% were normal, 40.5% indeterminate (22.0% incomplete; 18.5% minor abnormality), and 8.0% major abnormalities. Indeterminate findings were unrelated to age, race, parity, infertility, or psychiatric history, but associated with gestational age (26.6%/45.0%/52.5% for first/second/third trimesters; p < 0.001), and obesity (48.8 vs. 37.0%; p = 0.031). Pretest anxiety was highest in second/third trimesters (p = 0.029), and in subjects aged age ≤ 24 or younger(p < 0.001), with a history of anxiety (p < 0.001),) or with prior pregnancy loss (p = 0.011). Mean anxiety score decreased pre-to-posttest across all groups. Indeterminate findings were associated with higher PASS scores than normal findings: pretest 20.1 vs. 16.4 (p = 0.026) and posttest 16.9 vs. 12.2 (p = 0.009; adjusted-p = 0.01). Versus normal ultrasounds, incomplete findings were associated with higher post-ultrasound anxiety (p = 0.007; adjusted-p = 0.01) and smaller decreases from pre-to-posttest (adjusted-p = 0.03), whereas minor abnormalities had higher pretest anxiety (p = 0.029) with larger pre-to-posttest decreases (adjusted-p =0.010). DISCUSSION: Indeterminate ultrasounds, especially incomplete findings, are associated with significantly higher anxiety than normal findings, suggesting need for evidence-based counseling, management and strategies for decreasing number of indeterminate results.

Fetal CHD and perinatal outcomes.

OBJECTIVE: To evaluate delivery management and outcomes in fetuses prenatally diagnosed with CHD. STUDY DESIGN: A retrospective cohort study was conducted on 6194 fetuses (born between 2013 and 2016), comparing prenatally diagnosed with CHD (170) to those with non-cardiac (234) and no anomalies (5790). Primary outcomes included the incidence of preterm delivery and mode of delivery. RESULTS: Gestational age at delivery was significantly lower between the CHD and non-anomalous cohorts (38.6 and 39.1 weeks, respectively). Neonates with CHD had a significantly lower birth weights (p < 0.001). There was an approximately 1.5-fold increase in the rate of primary cesarean sections associated with prenatally diagnosed CHD with an odds ratio of 1.49 (95% CI 1.06-2.10). CONCLUSIONS: Our study provides additional evidence that the prenatal diagnosis of CHD is associated with a lower birth weight, preterm delivery, and with an increased risk of delivery by primary cesarean section.

Foetal right atrial aneurysm and aortic coarctation with left ventricular dysfunction.

Aneurysms of the right atrium are rare in the paediatric population. We report a case of a foetal diagnosis of right atrial aneurysm with associated atrial tachycardia in foetal and postnatal life. Unique to our case are the findings of isolated pericardial effusion without hydrops fetalis and the development of aortic coarctation in postnatal life.

Prenatal ABO/RHD Genotyping: A New Paradigm to Allow for Fresh Whole Blood for Cardiopulmonary Bypass in the Immediate Newborn Period.

Compared to standard component therapy, fresh whole blood (FWB) offers potential benefits to neonates undergoing cardiopulmonary bypass (CPB) in the context of open cardiac surgery: decreased blood loss and subsequent risk of volume overload, improved coagulation status, higher platelet counts during and following CPB, circumvention of limited vascular access, and significantly reduced donor exposures. Obtaining FWB, however, entails 2-5 days of preparation, which often precludes its availability for neonates requiring CPB in the immediate newborn period. Using a multidisciplinary approach and molecular ABO/RHD genotyping on amniotic fluid, we developed a protocol to allow procurement of FWB for timed delivery followed by open cardiac surgery. Eligible subjects include patients undergoing genetic amniocentesis following the diagnosis of a fetal cardiac anomaly likely to require open surgical repair in the initial days after birth. This protocol has been successfully implemented following prenatal diagnosis of severe fetal cardiac anomalies. Taking advantage of the prenatal time period and the ability to perform fetal blood typing prenatally using molecular genotyping makes possible a new paradigm for the availability of FWB for CPB to improve perioperative, short-term, and long-term outcomes in a population comprised of some of the smallest and sickest patients who will undergo CPB.

Non-rheumatic streptococcal myocarditis mimicking acute myocardial infarction in an adolescent male.

An adolescent male with a recent history of streptococcal pharyngitis presented with severe substernal chest pain, troponin leak, and ST-segment elevation, which are suggestive of acute inferolateral myocardial infarction. The coronary angiogram was normal. The patient was subsequently diagnosed with non-rheumatic streptococcal myocarditis. He was treated with amoxicillin and had excellent recovery. Non-rheumatic streptococcal myocarditis is an important mimic of acute myocardial infarction in young adults.

First-Trimester Fetal Echocardiography: Identification of Cardiac Structures for Screening from 6 to 13 Weeks' Gestational Age.

BACKGROUND: Early fetal echocardiography (FE), performed at 12 to 16 weeks' gestational age (GA), can be used to screen for fetal heart disease akin to that routinely performed in the second trimester. The efficacy of FE at earlier GAs has not been as well explored, particularly with recent advances in ultrasound technology. The aim of this study was to evaluate the efficacy of early FE in assessing fetal heart structure, and the added benefit of color Doppler (CD), from as early as 6 weeks through to 13+6 weeks' GA. METHODS: Pregnant women were prospectively recruited for first-trimester FE. All underwent two-dimensional (2D) cardiac imaging combined with CD assessment, and all were offered second-trimester fetal echocardiographic evaluations. Fetal cardiac anatomy was assessed both in real time during FE and additionally offline by two separate reviewers. RESULTS: Very early FE was performed in 202 pregnancies including a total of 261 fetuses, with 92% (n = 241) being reassessed at ≥18 weeks' GA. Mean GA at FE was 10+6 weeks (range, 6+1 to 13+6 weeks). Transabdominal scanning was used in all cases, and transvaginal scanning was used additionally in most at <11 weeks' GA (n = 103 of 117 [88%]). There was stepwise improvement in image resolution of the fetal heart in those pregnancies that presented at later gestation for assessment. CD assisted with definition of cardiac anatomy at all GAs. A four-chambered heart could be identified in 52% of patients in the eighth week (n = 12 of 23), improving to 80% (n = 36 of 45) in the 10th week and 98% (n = 57 of 58) by the 11th week. The inferior vena cava was visualized by 2D imaging in only 4% (n = 1 of 23) in the eighth week, increasing to 13% (n = 6 of 45) by the 10th week and 80% (n = 25 of 31) by the 13th week. CD improved visualization of the inferior vena cava at earlier GAs to >80% (n = 37 of 45) from 10 weeks. Pulmonary veins were not visualized by either 2D imaging or CD until after the 11th week. Both cardiac outflow tracts could be visualized by 2D imaging in the minority from 8+0 to 10+6 weeks (n = 18 of 109 [16%]) but were imaged in most from 11+0 to 13+6 weeks (n = 114 of 144 [79%]). CD imaging improved visualization of both outflow tracts to 64% (n = 29 of 45) in the 10th week. On 2D imaging alone, both the aortic and ductal arches were seen in only 29% of patients in the 10th week (n = 13 of 45), increasing to 58% when CD was used (58% [n = 26 of 45]) and to >80% (n = 47 of 58) using CD in the 11th week. CONCLUSIONS: Very early FE, from as early as 8 weeks, can be used to assess cardiac structures. The ability to image fetal heart structures between 6 and 8 weeks is currently nondiagnostic. The use of CD significantly increases the detection of cardiac structures on early FE. The ideal timing of complete early FE, excluding pulmonary vein assessment, appears to be after 11 weeks' GA.

Placental Characteristics of Fetuses With Congenital Heart Disease.

OBJECTIVES: To investigate whether there is an association between congenital heart disease (CHD) and placental abnormalities. METHODS: We conducted a case-control study that included cases of infants with CHD who underwent cardiac surgery within 6 months of life at the Johns Hopkins Medical Center from 2000 to 2013, and gestational age-matched normal pregnancy controls (200 neonates per group). RESULTS: Overall, abnormal placental cord insertion (ie, eccentric, marginal, or velamentous) was associated with CHD (odds ratio, 2.33-3.76). The main cardiac defects associated with abnormal cord insertion were conotruncal defects (relative risk, 3.08; 95% confidence interval [CI], 1.48-6.40; P = .003), left heart disease (relative risk, 2.40; 95% CI, 1.32-4.37; P = .004), and right heart disease (relative risk, 2.22; 95% CI, 1.21-4.07; P = .010). The Placenta-to-birth weight ratio was not associated with CHD. Intrauterine growth restriction was associated with CHD (odds ratio, 3.00; 95% CI, 1.41-6.39; P = .004). CONCLUSIONS: Abnormal cord insertion, as well as intrauterine growth restriction, was determined to be correlated with the presence of CHD. On the basis of our results, we conclude that cord insertion should be evaluated at routine obstetric sonography, and further fetal heart evaluation is warranted if abnormal cord insertion is detected.