Predictors of spontaneous pregnancy loss in single ventricle physiology.

BACKGROUND: Pregnant patients with single ventricle (SV) physiology carry a high risk of spontaneous pregnancy loss (SPL), yet the clinical factors contributing to this risk are not well defined. METHODS: Single-centre retrospective study of pregnant patients with SV physiology seen in cardio-obstetrics clinic over the past 20 years with chart review of their obstetric history. Patients without a known pregnancy outcome were excluded. Univariable Bayesian panel-data random effects logit was used to model the risk of SPL. RESULTS: The study included 20 patients with 44 pregnancies, 20 live births, 21 SPL and 3 elective abortions. All had Fontan palliation except for two with Waterston and Glenn shunts. 10 (50%) had a single right ventricle (RV). 14 (70%) had moderate or severe atrioventricular valve regurgitation (AVVR). Atrial arrhythmias were present in 16 (80%), Fontan-associated liver disease (FALD) in 15 (75%) and FALD stage 4 in 9 (45%). 12 (60%) were on anticoagulation. Average first-trimester oxygen saturation was 93.8% for live births and 90.8% for SPL. The following factors were associated with higher odds of SPL: RV morphology (OR 1.72 (95% credible interval (CrI) 1.0008-2.70)), moderate or severe AVVR (OR 1.64 (95% CrI 1.003-2.71)) and reduced first-trimester oxygen saturation (OR 1.83 (95% CrI 1.03-2.71) for each per cent decrease in O2 saturation. CONCLUSION: Pregnant patients with SV physiology, particularly those with RV morphology, moderate or severe AVVR, and lower first-trimester oxygen saturations, have a higher risk of SPL. Identifying these clinical risk factors can guide preconception counselling by the cardio-obstetrics team.

Outcomes of combined left bundle branch area pacing with atrioventricular nodal ablation in patients with atrial fibrillation and pulmonary disease.

INTRODUCTION: Concomitant left bundle branch area pacing (LBBAP) with atrioventricular (AV) nodal ablation is emerging as a viable management option in atrial fibrillation refractory to medical management. Its viability in patients with pulmonary disease and atrial fibrillation is unknown. METHODS AND RESULTS: This is a retrospective, observational cohort study in consecutive patients who underwent concomitant LBBAP with AV nodal ablation with advanced pulmonary disease at the Cleveland Clinic Fairview Hospital between January 2019 and January 2023. Patient characteristics, comorbidities, and medication use were extracted via chart review. Rates of hospitalizations, medication use, and structural disease seen on echocardiography were compared before and after the procedure. There were 27 patients with group 3 pulmonary hypertension who underwent the procedure. In the 24 months preprocedure, there were 114 admissions for heart failure or atrial fibrillation compared to 9 admissions postprocedure (p < .001). Mean follow up was 17.3 ± 12.1 months. There were no significant complications or lead dislodgements. Echocardiographic characteristics were similar prior to and after pacemaker implantation. Use of medications for rate and rhythm control was common preprocedure, and was reduced dramatically postprocedure. CONCLUSION: This small, retrospective cohort study suggests concomitant LBBAP with AV nodal ablation may be safe and efficacious for management of atrial fibrillation in patients with advanced pulmonary disease.

Characteristics of sudden death by clinical criteria.

Sudden death is a leading cause of deaths nationally. Definitions of sudden death vary greatly, resulting in imprecise estimates of its frequency and incomplete knowledge of its risk factors. The degree to which time-based and coronary artery disease (CAD) criteria impacts estimates of sudden death frequency and risk factors is unknown. Here, we apply these criteria to a registry of all-cause sudden death to assess its impact on sudden death frequency and risk factors. The sudden unexpected death in North Carolina (SUDDEN) project is a registry of out of-hospital, adjudicated, sudden unexpected deaths attended by Emergency Medical Services. Deaths were not excluded by time since last seen or alive or by prior symptoms or diagnosis of CAD. Common criteria for sudden death based on time since last seen alive (both 24 hours and 1 hour) and prior diagnosis of CAD were applied to the SUDDEN case registry. The proportion of cases satisfying each of the 4 criteria was calculated. Characteristics of victims within each restrictive set of criteria were measured and compared to the SUDDEN registry. There were 296 qualifying sudden deaths. Application of 24 hour and 1 hour timing criteria compared to no timing criteria reduced cases by 25.0% and 69.6%, respectively. Addition of CAD criteria to each timing criterion further reduced qualifying cases, for a total reduction of 81.8% and 90.5%, respectively. However, characteristics among victims meeting restrictive criteria remained similar to the unrestricted population. Timing and CAD criteria dramatically reduces estimates of the number of sudden deaths without significantly impacting victim characteristics.

Peritraumatic Plasma Omega-3 Fatty Acid Concentration Predicts Chronic Pain Severity Following Thermal Burn Injury.

Chronic pain is a significant comorbidity of burn injury affecting up to 60% of survivors. Currently, no treatments are available to prevent chronic pain after burn injury. Accumulating evidence suggests that omega-3 fatty acids (O3FAs) improve symptoms across a range of painful conditions. In this study, we evaluated whether low peritraumatic levels of O3FA predict greater pain severity during the year after burn injury. Burn survivors undergoing skin autograft were recruited from three participating burn centers. Plasma O3FA (n = 77) levels were assessed in the early aftermath of burn injury using liquid chromatography/mass spectrometry, and pain severity was assessed via the 0 to 10 numeric rating scale for 1 year following burn injury. Repeated-measures linear regression analyses were used to evaluate the association between peritraumatic O3FA concentrations and pain severity during the year following burn injury. Peritraumatic O3FA concentration and chronic pain severity were inversely related; lower levels of peritraumatic O3FAs predicted worse pain outcomes (ß = -0.002, P = .020). Future studies are needed to evaluate biological mechanisms mediating this association and to assess the ability of O3FAs to prevent chronic pain following burn injury.

microRNA-mRNA Profile of Skeletal Muscle Differentiation and Relevance to Congenital Myotonic Dystrophy.

microRNAs (miRNAs) regulate messenger RNA (mRNA) abundance and translation during key developmental processes including muscle differentiation. Assessment of miRNA targets can provide insight into muscle biology and gene expression profiles altered by disease. mRNA and miRNA libraries were generated from C2C12 myoblasts during differentiation, and predicted miRNA targets were identified based on presence of miRNA binding sites and reciprocal expression. Seventeen miRNAs were differentially expressed at all time intervals (comparing days 0, 2, and 5) of differentiation. mRNA targets of differentially expressed miRNAs were enriched for functions related to calcium signaling and sarcomere formation. To evaluate this relationship in a disease state, we evaluated the miRNAs differentially expressed in human congenital myotonic dystrophy (CMD) myoblasts and compared with normal control. Seventy-four miRNAs were differentially expressed during healthy human myocyte maturation, of which only 12 were also up- or downregulated in CMD patient cells. The 62 miRNAs that were only differentially expressed in healthy cells were compared with differentiating C2C12 cells. Eighteen of the 62 were conserved in mouse and up- or down-regulated during mouse myoblast differentiation, and their C2C12 targets were enriched for functions related to muscle differentiation and contraction.

Obesity increases the risk of chronic pain development after motor vehicle collision.

Obesity has been found to increase the risk of musculoskeletal pain (MSP) in other settings, but to our knowledge, the influence of increased body mass index on pain outcomes after common trauma exposures such as motor vehicle collision (MVC) has not been assessed. In addition, obesity results in biomechanical changes, as well as physiologic changes including reduced hypothalamic pituitary adrenal axis negative feedback inhibition, but mechanisms by which obesity may result in worse post-traumatic outcomes remain poorly understood. In this study, we evaluated the influence of body mass index on axial and overall MSP severity (0-10 numeric rating scale) 6 weeks, 6 months, and 1 year after MVC among 917 European Americans who presented to the emergency department for initial evaluation. After adjusting for an array of sociodemographic factors, obesity (particularly morbid obesity) was an independent risk factor for worse MSP after MVC (eg, RR 1.41 [95% CI 1.11, 1.80] for moderate or severe MSP 6 months after MVC among morbidly obese vs normal weight MVC survivors). Interestingly, substantial effect modification was observed between obesity risk and a genetic variant known to reduce hypothalamic pituitary adrenal axis negative feedback inhibition (FKBP5 rs9380526). (eg, 41% vs 16% increased risk of moderate or severe MSP at 6 months among obese individuals with and without the risk allele.) Further studies are needed to elucidate mechanisms underlying chronic pain development in obese trauma survivors and to develop interventions that will reduce chronic pain severity among this common, at-risk group.