Citations

Abstract OBJECTIVES Limited literature is available on the best management strategy for tricuspid valve (TV) disease in adults. We sought to review our long-term outcomes of TV surgery with regard to survival and reoperation. METHODS A retrospective analysis of all patients ≥18 years of age [n = 2541, aged 67 ± 13years, 1433 (56%) females] who underwent first-time TV surgery between January 1993 and December 2013 was done. There were 1735 patients who received TV repair and 806 patients underwent replacement. A gradient boosting machine model was used to derive a propensity score for predicting replacement using 27 preoperative characteristics. Four hundred and eighteen propensity-matched pairs of TV repair and replacement were identified. Cox proportional hazard regression was used on the matched subset to determine the effect of replacement. RESULTS Functional TV regurgitation was present in 54% (n = 1369). A bioprosthesis was used in 84% (n = 680) of replacements, while 54% (n = 934) of TV repairs were ring annuloplasties. Operative mortality was 8% (n = 212). Overall survival was 54%, 29% and 13% at 5, 10 and 15 years, respectively. After propensity score matching, replacement was significantly associated with increased mortality [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.18–2.00; P = 0.001]. The cumulative incidence of TV reoperation was similar between the 2 groups when accounting for the competing risk of death [Fine–Gray HR 1.56, 95% CI 0.9–2.8; P = 0.144]. CONCLUSIONS TV surgery is associated with poor outcomes due to multiple patient comorbidities. TV repair results in better survival compared to replacement in patients with similar comorbidities with no increased risk of getting a reoperation.

ABSTRACT Normal vitamin D homeostasis is critical for optimal health; nevertheless, vitamin D deficiency is a worldwide public health problem. Vitamin D insufficiency is most commonly due to inadequate cutaneous synthesis of cholecalciferol and/or insufficient intake of vitamin D, but can also arise as a consequence of pathological states such as obesity. Serum concentrations of 25(OH)D (calcidiol) are low in obesity, and fail to increase appropriately after vitamin D supplementation. Although sequestration of vitamin D in adipose tissues or dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients has been proposed to explain these findings, here we investigate the alternative mechanism that reduced capacity to convert parent vitamin D to 25(OH)D due to decreased expression of CYP2R1, the principal hepatic vitamin D 25-hydroxylase. To test this hypothesis, we isolated livers from female mice of 6 to 24 weeks of age, weaned onto either a normal chow diet or a high-fat diet, and determined the abundance of Cyp2r1 mRNA using digital droplet-quantitative PCR. We observed a significant (p < 0.001) decrease in Cyp2r1 mRNA in the liver of high-fat diet–fed mice relative to lean-chow–fed female mice. Moreover, there was a significant (p < 0.01) relationship between levels of Cyp2r1 mRNA and serum 25(OH)D concentrations as well as between Cyp2R1 mRNA and the ratio of circulating 25(OH)D3 to cholecalciferol (p < 0.0001). Using linear regression we determined a curve with 25(OH)D3/cholecalciferol versus normalized Cyp2R1 mRNA abundance with an R2 value of 0.85. Finally, we performed ex vivo activity assays of isolated livers and found that obese mice generated significantly less 25(OH)D3 than lean mice (p < 0.05). Our findings indicate that expression of CYP2R1 is reduced in obesity and accounts in part for the decreased circulating 25(OH)D. © 2019 American Society for Bone and Mineral Research.

Objective To present 6‐month safety and effectiveness data from a multicentre prospective study of aquablation in men with lower urinary tract symptoms (LUTS) attributable to benign prostatic hyperplasia ( BPH ) with prostate volumes between 80 and 150 mL. Methods Between September and December 2017, 101 men with LUTS attributable to BPH were prospectively enrolled at 16 centres in Canada and the USA. Results The mean prostate volume was 107 mL. The mean length of hospital stay after the aquablation procedure was 1.6 days (range: same day to 6 days). The primary safety endpoint (Clavien–Dindo grade 2 or higher or any grade 1 event resulting in persistent disability) at 3 months occurred in 45.5% of men, which met the study design goal of < 65% ( P < 0.001). At 6 months, 22% of the patients had experienced a Clavien–Dindo grade 2, 14% a grade 3 and 5% a grade 4 adverse event. Bleeding complications requiring intervention and/or transfusion were recorded in eight patients prior to discharge and in six patients after discharge. The mean International Prostate Symptom Score improved from 23.2 ± 6.3 at baseline to 6.7 ± 5.1 at 3 months, meeting the study's primary efficacy endpoint goal ( P < 0.001). The maximum urinary flow rate increased from 8.7 to 18.8 mL/s ( P < 0.001) and post‐void residual urine volume decreased from 131 at baseline to 47 at 6 months ( P < 0.0001). At 6 months, prostate‐specific antigen concentration reduced from 7.1 ± 5.9 ng/mL at baseline to 4.0 ± 3.9 ng/mL, a 44% reduction. Conclusions Aquablation is safe and effective in treating men with larger prostates (80–150 mL), without significant increase in procedure or resection time.

Objective Long QT syndrome (LQTS) is a known cause of unexpected death, leading some to recommend routine neonatal electrocardiographic (ECG) screening. We used continuous electronic heart rate corrected QT interval (QTc) monitoring to screen for interval prolongation in a cohort of hospitalized neonates to identify those at a risk of having LQTS. We hypothesized that this screening method would yield an acceptable positive predictive value (PPV). Study Design A cohort of 589 infants hospitalized in a level II neonatal intensive care unit were screened through continuous electronic QTc monitoring linked to an investigator-designed, computerized data sniffer. Screening was conducted from days-of-life 3 through 7 or until hospital discharge. The data sniffer alerted investigators for a 24-hour average QTc of ≥475 ms. Positively screened patients were further evaluated with 12-lead ECG. Results Positive screens were obtained in 5.6% of patients, all of whom had negative follow-up ECG testing (PPV = 0%). Furthermore, one-quarter of positively screened neonates underwent echocardiography based on ECG findings, none of which identified clinically relevant pathology. Conclusion Electronic monitoring of QTc in hospitalized neonates during the first week of life was not an efficient way to identify those at a risk of having LQTS. Conversely, screening triggered unnecessary testing.

Aim Angina pectoris in the absence of obstructive coronary artery disease (CAD) is common and is associated with poor quality of life (QOL). Coronary microvascular endothelial dysfunction is associated with myocardial ischaemia and is a common cause of angina. We hypothesise that evaluation of coronary endothelial function, its diagnosis and treatment will favourably impact QOL in patients with angina symptoms and non-obstructive CAD. Methods and results Follow-up was done on 457 patients with chest pain and non-obstructive coronary arteries who had undergone coronary vascular reactivity evaluation by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4±4.7 years, QOL was assessed by administration of the SF-36 QOL survey. Patients diagnosed and treated for microvascular endothelial dysfunction had a higher (better) overall mental composite score (44.8 vs 40.9, p=0.036) and mental health score (44.2 vs 40.7, p=0.047), and a trend towards higher vitality scores (39.1 vs 35.9, p=0.053) and role emotional scores (43.6 vs 40.4, p=0.073), compared with patients with normal endothelial function. Conclusion Among patients with chest pain and normal coronaries, diagnosis and treatment of coronary microvascular endothelial dysfunction in those with angina pectoris and non-obstructive CAD are associated with better QOL compared with patients with normal endothelial function.

Introduction: Accurately balancing risks of interventional treatment and intracranial hemorrhage (ICH) in the untreated course of unruptured brain arteriovenous malformation (uBAVM) patients is critical for optimal management. Observational studies of uBAVM afford an opportunity to address important gaps and previous criticisms of randomized data to help guide treatment decisions and assess long-term risk/benefit ratio. We previously published an individual patient data meta-analysis (IPDMA) in 4 MARS cohorts and identified ICH presentation and increasing age as significant predictors of ICH during follow-up, but was not powered to detect predictors in those with uBAVM. Thus, the goals of this project are to identify risk factors for ICH in uBAVMs, to estimate the risk with precision, and to create personalized, risk-prediction models. Methods: MARS is an international, multi-center study of 11 cohorts with target enrollment of 4,500 uBAVM patients ascertained through population-based or referral-based studies. We are harmonizing both retrospective and prospective data, including clinical, lifestyle, imaging, and angiographic factors. Treatments, complications, and functional outcomes (physician and patient-reported) will be updated annually between 2018-2022. We propose to: 1) identify predictors of outcome in uBAVMs using IPDMA; 2) test whether long-term outcomes differ by treatment using statistical approaches for causal inference and unbiased estimates; 3) compare treatment outcomes in randomized and non-randomized data to address generalizability; and 4) validate models and provide a novel tool for calculating individualized risks. Eligible sites have: a) prior BAVM publications; b) data from a minimum of 100 uBAVM patients; c) agree to random outcome adjudication; and d) agree to MARS data sharing policy. Discussion: The NIH-funded MARS consortium will provide important and comprehensive characterization of the untreated and treated course of uBAVMs, using large observational datasets and sophisticated epidemiological approaches. The data and models generated will be a useful resource for decision-making. We welcome participation from eligible sites with longitudinal data on uBAVM patients

Introduction: A 3.4% (95% CI: 2.1% to 4.7%) higher peri-procedural stroke and death risk has been previously documented for those treated with carotid artery stenting (CAS) relative to those treated with carotid endarterectomy (CEA). However, the CAS versus CEA treatment differences in long-term outcomes and the post-procedure durability have not been described. Methods: Data from the 4 largest CAS-versus-CEA randomized trials for treatment of symptomatic carotid atherosclerosis (EVA-3S, SPACE, ICSS, and CREST) were pooled, and treatment differences assessed for the outcome of any stroke or death during a 120-day peri-procedural period, plus ipsilateral stroke afterward. Results: Long-term follow-up was analysed for 4754 patients. Median length of follow-up across the studies ranged from 2.0 to 6.9 years, with 88 peri-procedural and 55 post-procedural events among those CEA-treated, and 169 and 64 for those CAS-treated. After the peri-procedural period, the annual rates of stroke following CAS was 0.6% (95% CI: 0.5 to 0.8) and following CEA 0.6% (95% CI: 0.5 to 0.8), resulting in non-significant durability differences of less than 1% over the period extending up to 9 years (see Table). The previously-documented 3.4% higher peri-procedural event rate in the CAS group contributed to a significant 3.1% (95% CI: 1.6% to 4.7%) treatment difference at 1-year, and the aforementioned similar durability implied that this significant difference remained relatively constant over the period extending up to 9 years (see table). Conclusions: The post-procedure durability of CAS and CEA were similar, both with event rates below 1%. The similarity of post-procedure events rates implies that the previously-documented higher peri-procedural in the CAS group is “carried forward” with a higher risk of outcomes extending to 9-years.