Dronedarone for the Treatment of Atrial Arrhythmias in Adults With Congenital Heart Disease.

BACKGROUND: Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity. METHODS: A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed. RESULTS: The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included ß-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months. CONCLUSION: Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.

Autoimmune rheumatic diseases in women with coronary microvascular dysfunction: a report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project.

Background: While autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history. Methods: Women with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis. Results: Of the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups. Conclusions: Among women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.

Imaging and guiding intervention for tricuspid valve disorders using 3-dimensional transesophageal echocardiography in pediatric and congenital heart disease.

In the pediatric and congenital heart disease (CHD) population, tricuspid valve (TV) disorders are complex due to the variable TV morphology, its sophisticated interaction with the right ventricle as well as associated congenital and acquired lesions. While surgery is the standard of care for TV dysfunction in this patient population, transcatheter treatment for bioprosthetic TV dysfunction has been performed successfully. Detailed and accurate anatomic assessment of the abnormal TV is essential in the preoperative/preprocedural planning. Three-dimensional transthoracic and 3D transesophageal echocardiography (3DTEE) provides added value to 2-dimensional imaging in the characterization of the TV to guide therapy and 3DTEE serves as an excellent tool for intraoperative assessment and procedural guidance of transcatheter treatment. Notwithstanding advances in imaging and therapy, the timing and indication for intervention for TV disorders in this population are not well defined. In this manuscript, we aim to review the available literature, provide our institutional experience with 3DTEE, and briefly discuss the perceived challenges and future directions in the assessment, surgical planning, and procedural guidance of (1) congenital TV malformations, (2) acquired TV dysfunction from transvenous pacing leads, or following cardiac surgeries, and (3) bioprosthetic TV dysfunction.

Continuous-Flow Ventricular Assist Device Support in Adult Congenital Heart Disease: A 15-Year, Multicenter Experience of Temporary and Durable Support.

Heart failure (HF) is common in adult congenital heart disease (ACHD) patients; however, use of continuous-flow ventricular assist devices (CF-VADs) remains rare. We reviewed outcomes of patients with congenital heart disease greater than or equal to 18 years of age at the time of CF-VAD implant at the affiliated pediatric and adult institutions between 2006 and 2020. In total, 18 ACHD patients (15 with great anatomical complexity) received 21 CF-VADs. Six patients (median age 34 years) received seven percutaneous CF-VADs with a median duration of support of 20 days (3-44 days) with all patients survived to hospital discharge and two patients were bridged to durable CF-VADs. Fourteen patients (median age 38 years) received durable CF-VADs. Thirteen patients (93%) survived to hospital discharge and the median duration of support was 25.8 months (6.4-52.1 months). Estimated survival on durable CF-VAD at 1, 3, and 5 years was 84%, 72%, and 36%, respectively. Three patients were successfully bridged to transplantation. Device-related complications include cerebrovascular accident (n = 5), driveline infection (n = 3), device infection requiring chronic antibiotic therapy (n = 4), gastrointestinal bleeding (n = 6), and presumed pump thrombosis (n = 5). These results show percutaneous and durable CF-VADs can support ACHD patients with advanced HF.

A Multisite Retrospective Review of Direct Oral Anticoagulants Compared to Warfarin in Adult Fontan Patients.

PURPOSE: Direct oral anticoagulants (DOACs) are not recommended in adult Fontan patients (Level of Evidence C). We hypothesized that DOACs are comparable to warfarin and do not increase thrombotic and embolic complications (TEs) or clinically significant bleeds. METHODS: We reviewed the medical records of adult Fontan patients on DOACs or warfarin at three major medical centers. We identified 130 patients: 48 on DOACs and 107 on warfarin. In total, they were treated for 810 months on DOACs and 5637 months on warfarin. RESULTS: The incidence of TEs in patients on DOACs compared to those on warfarin was not increased in a statistically significant way (hazard ratio [HR] 1.7 and p value 0.431). Similarly, the incidence of nonmajor and major bleeds in patients on DOACs compared to those on warfarin was also not increased in a statistically significant way (HR for nonmajor bleeds in DOAC patients was 2.8 with a p value of 0.167 and the HR for major bleeds was 2.0 with a p value 0.267). In multivariate analysis, congestive heart failure (CHF) was a risk factor for TEs across both groups (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.6) and bleed history was a risk factor for clinically significant bleeds (OR = 6.8, 95% CI = 2.7-17.2). CONCLUSION: In this small, retrospective multicenter study, the use of DOACs did not increase the risk of TEs or clinically significant bleeds compared to warfarin in a statistically significant way.

The Role of Health Literacy in Prostate Cancer Screening.

OBJECTIVE: To determine if there is an association between self-reported health literacy and rates of prostate cancer screening through PSA testing. METHODS: This secondary data analysis utilized information from the 2016 Behavioral Risk Factor Surveillance System (BRFSS). The primary exposure was self-reported health literacy, and the primary outcome was whether patients underwent prior PSA testing. Males 55-69 years old from 13 states were included in the study and were excluded if they had any missing data. Participants were categorized into low, moderate, or high level of health literacy. Confounders were adjusted for using binary logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: A total of 12,149 participants were included. Five percent of participants reported low health literacy, 54% moderate health literacy, and 41% high health literacy. Compared with study participants who self-reported high levels of health literacy, the odds of undergoing PSA testing were 59% lower in those with low health literacy (OR 0.41; 95% CI 0.28-0.64) and 30% lower in those with moderate health literacy (OR 0.70; 95% CI 0.60-0.83). CONCLUSIONS: Our research demonstrates a positive association between self-reported health literacy and the likelihood of PSA screening. While PSA screening can be controversial, health literacy may serve as a window into which patients are more likely to be proactive in their urologic care. Future studies examining how health literacy effects other urologic conditions is necessary.

An industrial approach towards solid dosage development for first-in-human studies: Application of predictive science and lean principles.

Tablet development is challenging during early clinical phases of drug discovery because of dose uncertainty, limited active pharmaceutical ingredient availability, and short lead times. Here, we introduce a new framework to expedite product development using a suite of in-house and commercially available predictive tools developed through the integration of computer modelling and material-sparing characterisation methods. The strategy underpins the use of dry granulation for formulation development with guidance on scale-up and manufacturability to achieve 'First Time Right'. We present an analytical strategy based on predictive science with a focus on stability, and shelf-life related attributes to assure product quality. Thus, we provide a holistic approach towards robust, scientific product development through integrated project knowledge and risk-based approaches, delivering significant savings in both material and resources.

Platypnea-Orthodeoxia Syndrome Caused by an Intracardiac Shunt.

Platypnea-orthodeoxia syndrome, a rare condition characterized by posture-related dyspnea, is usually caused by an intracardiac shunt, hepatopulmonary syndrome, or shunting resulting from severe pulmonary disease. We report the case of a 33-year-old woman who presented with increasing dyspnea and oxygen desaturation when she sat up or arose. Our diagnosis was platypnea-orthodeoxia syndrome. A lead of a previously implanted pacemaker exacerbated a severe tricuspid regurgitant jet that was directed toward the patient's intra-atrial septum. Percutaneous closure of a small secundum atrial septal defect eliminated right-to-left shunting and substantially improved the patient's functional status. In addition to this case, we discuss this unusual condition.

Precision Medicine in Lung Cancer Treatment.

Lung cancer remains second most common cancer in men and women in the United States. More than 50% of patients are diagnosed in the advanced stage. Traditionally, chemotherapy has been the backbone of management of stage IV lung cancer. A better understanding of the molecular pathogenesis has led to rapid development of targeted therapy and immunotherapy. This has led to significant improvement in survival of patients with lung cancer stages III to IV. These drugs are being studied in early stage lung cancer. Several trials are ongoing to improve the survival and quality of life of our patients.

Saline Contrast Transesophageal Echocardiography in Fontan Patients: Assessment of the Presence, Type, and Size of Right to Left Shunts.

Right to left (R-L) shunts resulting in cyanosis or systemic embolization occur after the Fontan procedure. The primary modality of diagnosing these is angiography. Successful delineation of these shunts in Fontan patients using selective saline contrast transesophageal echocardiography (SCTEE) may allow for reduced radiation and contrast exposure. We hypothesized that SCTEE could accurately determine the presence, type, and semiquantitative shunt size of R-L shunts in Fontan patients. SCTEE was performed in Fontan patients undergoing angiography for clinical indications. Injections were performed in six sites: mid-Fontan, right and left pulmonary arteries, superior and inferior vena cavae, and innominate vein. R-L shunt size was subjectively graded as 0 = absent, 1 = small, and 2 = medium or large based on echo contrast density in the left atrium. SCTEE was compared to angiography. 33 patients with Fontan were studied with median age 15 years, median weight 50.1 kg, and median O2 saturation of 90% in the R-L shunt group and 95% in the no R-L shunt group. R-L shunt types included intracardiac shunts (ICS), veno-venous collaterals (VVCs), arteriovenous malformations (AVMs), and their combinations. SCTEE versus angiography results were the same for the presence, type, and size of R-L shunts in 79% (26/33). SCTEE identified shunts in 88% (29/33). Angiography identified shunts in 85% (28/33). Neither method missed any medium or large R-L shunts. SCTEE and angiography had similar accuracy. SCTEE accurately detected the presence, type, and size of R-L shunts in most Fontan patients in this study. This can be used to guide targeted angiography, reducing radiation exposure and contrast load.

Guidewire pacing during transcatheter aortic valve implantation in a patient with complex congenital heart disease.

We present a case of temporary guidewire pacing in a patient with Fontan anatomy during transcatheter aortic valve implantation. Temporary pacing was successfully achieved utilizing this method without complications. There is an increasing population of patients with complex congenital heart disease and expanding variety of transcatheter interventions. Due to limitations in vascular access and surgical anatomies, guidewire pacing may have a wide array of potential applications in pediatrics and the congenital heart disease population.

The Prevalence of Psychiatric Disorders Among Elective Plastic Surgery Patients.

Purpose: Psychiatric disorder is one of the predictors of poor outcome in cosmetic plastic surgery patients. A US study in 1960 showed that 72.4% of 98 cosmetic plastic surgery patients had a psychiatric disorder. In our study, we predict that the prevalence of psychiatric disorders will be statistically significant among patients seeking elective plastic surgery in comparison with the general US population. Methods: We conducted a retrospective review study of 1000 adult patients seeking elective plastic surgery at The University of Kansas Medical Center Plastic Surgery Department from 2011 to 2016. Results: From 1000 patients seeking elective plastic surgery procedure, 441 (44.1%) patients have or had a history of psychiatric disorder. Most common psychiatric disorders were major depressive disorder (n = 223; 50.6%) and generalized anxiety disorder (n = 145; 32.9%). Conclusion: Our study indicates that psychiatric disorders are prevalent in patients seeking elective plastic surgery at our institution. Anxiety and depression were the most common diagnoses, and this is possibly due to these being the most common psychiatric disorders in the US population. Results highlight the importance of provider vigilance for psychiatric patients seeking elective plastic surgery.