Serum Testosterone and Dihydrotestosterone and Incidence and Progression of Lower Urinary Tract Symptoms: Results From the REDUCE Study.

PURPOSE: Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support this idea. We tested if elevated serum testosterone or dihydrotestosterone were risk factors for lower urinary tract symptoms incidence in asymptomatic men and for lower urinary tract symptoms progression in symptomatic men. MATERIALS AND METHODS: A post hoc analysis of REDUCE was performed in 3009 asymptomatic men and in 2145 symptomatic men. REDUCE was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated prostate-specific antigen and negative prestudy biopsy. We estimated multivariable adjusted hazard ratios and 95% confidence intervals using Cox models to test the association between quintiles of serum testosterone and dihydrotestosterone at baseline and lower urinary tract symptoms incidence and progression and tested for interaction by treatment arm (dutasteride vs placebo). RESULTS: In asymptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms incidence (P = .9, P = .4). In symptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms progression (P = .9, P = .7). Results were similar in both placebo and dutasteride arms (all P interaction ≥ .3). CONCLUSIONS: In REDUCE, higher serum testosterone and higher serum dihydrotestosterone were not associated with either lower urinary tract symptoms incidence in asymptomatic men or lower urinary tract symptoms progression in symptomatic men. These data do not support the hypothesis that serum androgens in middle-aged men are associated with lower urinary tract symptoms.

Proactive esophageal cooling protects against thermal insults during high-power short-duration radiofrequency cardiac ablation.

BACKGROUND: Proactive cooling with a novel cooling device has been shown to reduce endoscopically identified thermal injury during radiofrequency (RF) ablation for the treatment of atrial fibrillation using medium power settings. We aimed to evaluate the effects of proactive cooling during high-power short-duration (HPSD) ablation. METHODS: A computer model accounting for the left atrium (1.5 mm thickness) and esophagus including the active cooling device was created. We used the Arrhenius equation to estimate the esophageal thermal damage during 50 W/ 10 s and 90 W/ 4 s RF ablations. RESULTS: With proactive esophageal cooling in place, temperatures in the esophageal tissue were significantly reduced from control conditions without cooling, and the resulting percentage of damage to the esophageal wall was reduced around 50%, restricting damage to the epi-esophageal region and consequently sparing the remainder of the esophageal tissue, including the mucosal surface. Lesions in the atrial wall remained transmural despite cooling, and maximum width barely changed (<0.8 mm). CONCLUSIONS: Proactive esophageal cooling significantly reduces temperatures and the resulting fraction of damage in the esophagus during HPSD ablation. These findings offer a mechanistic rationale explaining the high degree of safety encountered to date using proactive esophageal cooling, and further underscore the fact that temperature monitoring is inadequate to avoid thermal damage to the esophagus.

Medical Students' Progress in Detecting and Interpreting Visual and Auditory Clinical Findings.

Phenomenon: Detection of visual and auditory clinical findings is part of medical students' core clinical performance abilities that a medical education curriculum should teach, assess, and remediate. However, there is a limited understanding of how students develop these skills. While training physical exam technical skills has received significant attention and emphasis, teaching and assessing medical students' ability to detect and interpret visual and auditory clinical findings skills has been less systematic. Therefore, the purpose of this study is to investigate how medical students' visual and auditory clinical findings skills progress and develop over their four years of undergraduate medical education. This study will provide educators insights that can guide curriculum refinements that lead to improving students' abilities in this area. Approach: A computer-based progress exam was created to measure the longitudinal development of students' abilities to detect and interpret visual and auditory findings. After pilot testing, sixty test items were developed in collaboration with six clinical faculty members and two medical education researchers. The exam includes detection and description of ECG, x-ray, heart sounds, breath sounds, skin lesions, and movement findings. The exam was administered to students at the beginning of each training year since 2014. Additionally, the exam was administered to the Class of 2017 prior to their graduation. Measurement validity and reliability tests were conducted. Descriptive statistics and ANOVA were used to determine progress. Findings: More than 98% of students in four years of training completed the exam each year. The exam instrument had high reliabilities and demonstrated acceptable concurrent validity when compared with other academic performance data. Findings showed that students' visual and auditory clinical findings skills increased each training year until their fourth year. There was no performance improvement between incoming Year 4 students and graduating Year 4 students. While group means increased, class performance did not become more homogeneous across four years. Longitudinal data showed the same performance patterns as the cross-sectional data. Performance of the bottom quartile of graduating fourth-year students was not significantly higher than the performance of the top quartile of incoming first-year students who had not had formal medical training. Insights: A longitudinal study to follow learners' performance in detecting and interpreting visual and auditory clinical findings can provide meaningful insights regarding the effects of medical training programs on performance growth. The present study suggests that our medical curriculum is not effective in bringing all students to a higher level of performance in detecting and interpreting visual and auditory clinical findings. This study calls for further investigation how medical students can develop visual and auditory detection and interpretation skills in undergraduate medical education. There is a need for planned curriculum and assessment of medical students' skills in detecting and interpreting visual and auditory clinical findings.

Percutaneous left ventricular assist device support during ablation of ventricular tachycardia: A meta-analysis of current evidence.

INTRODUCTION: Catheter ablation of ventricular tachycardia (VT) can be an effective therapy to reduce VT burden, but often it is limited by the potential for hemodynamic instability. Percutaneous left ventricular assist devices (pLVADs) have been used to maintain hemodynamic support during VT ablation but the evidence regarding its clinical impact has been inconclusive. METHODS AND RESULTS: We sought to assess the clinical impact of pLVAD when used in VT ablation by conducting a meta-analysis of the current evidence. We searched Pubmed and found nine observational studies that compared clinical outcomes of VT ablation in patients with pLVAD support to controls with no pLVAD support. The pooled data did not show a significant difference in mortality between both groups, nor a difference in acute procedural success or in recurrence of VT. There was also no difference in the number of patients receiving a cardiac transplant or being enrolled in the transplant list. Although there was no difference in the ablation time between the groups, patients in the pLVAD group had a longer total procedural time and more procedure-related adverse effects. CONCLUSION: This meta-analysis did not show clinical benefits from using pLVAD support during VT ablation, whereas it was associated with longer procedure times and more complications. This study was, however, limited by the observational nature of the data. In view of these data, the risk and benefit of pLVAD support during VT ablation should be considered on an individual basis.

Evaluation of alpha and gamma aluminum oxide nanoparticle accumulation, toxicity, and depuration in Artemia salina larvae.

In this study, Artemia salina (crustacean filter feeders) larvae were used as a test model to investigate the toxicity of aluminum oxide nanoparticles (Al2O3 NPs) on marine microorganisms. The uptake, toxicity, and elimination of α-Al2O3 (50 nm and 3.5 µm) and γ-Al2O3 (5 nm and 0.4 µm) NPs were studied. Twenty-four and ninety-six hour exposures of different concentrations of Al2O3 NPs to Artemia larvae were conducted in a seawater medium. When suspended in water, Al2O3 NPs aggregated substantially with the sizes ranging from 6.3 nm to >0.3 µm for spherical NPs and from 250 to 756 nm for rod-shaped NPs. The phase contrast microscope images showed that NPs deposited inside the guts as aggregates. Inductively coupled plasma mass spectrometry analysis showed that large particles (3.5 µm α-Al2O3) were not taken up by Artemia, whereas fine NPs (0.4 µm γ-Al2O3) and ultra-fine NPs (5 nm γ-Al2O3 and 50 nm α-Al2O3) accumulated substantially. Differences in toxicity were detected as changing with NP size and morphology. The malondialdehyde levels indicated that smaller γ-Al2O3 (5 nm) NPs were more toxic than larger γ-Al2O3 (0.4 µm) particulates in 96 h. The highest mortality was measured as 34% in 96 h for γ-Al2O3 NPs (5 nm) at 100 mg/L (LC50 > 100 mg/L). γ-Al2O3 NPs were more toxic than α-Al2O3 NPs at all conditions.

Accumulation and toxicity of CuO and ZnO nanoparticles through waterborne and dietary exposure of goldfish (Carassius auratus).

Dietary and waterborne exposure to copper oxide (CuO) and zinc oxide (ZnO) nanoparticles (NPs) was conducted using a simplified model of an aquatic food chain consisting of zooplankton (Artemia salina) and goldfish (Carassius auratus) to determine bioaccumulation, toxic effects, and particle transport through trophic levels. Artemia contaminated with NPs were used as food in dietary exposure. Fish were exposed to suspensions of the NPs in waterborne exposure. ICP-MS analysis showed that accumulation primarily occurred in the intestine, followed by the gills and liver. Dietary uptake was lower, but was found to be a potential pathway for transport of NPs to higher organisms. Waterborne exposure resulted in about a 10-fold higher accumulation in the intestine. The heart, brain, and muscle tissue had no significant Cu or Zn. However, concentrations in muscle increased with NP concentration, which was ascribed to bioaccumulation of Cu and Zn released from NPs. Free Cu concentration in the medium was always higher than that of Zn, indicating CuO NPs dissolved more readily. ZnO NPs were relatively benign, even in waterborne exposure (p ≥ 0.05). In contrast, CuO NPs were toxic. Malondialdehyde levels in the liver and gills increased substantially (p < 0.05). Despite lower Cu accumulation, the liver exhibited significant oxidative stress, which could be from chronic exposure to Cu ions.

Investigating trends in interest for benign prostatic hyperplasia surgery options using Google Trends.

Understanding patient interest among surgical options is challenging. We used Google Trends to analyze interest in benign prostatic hyperplasia (BPH) surgeries recommended for prostate volumes <80 cc. Google Trends was queried with five BPH surgeries. Final rank of search terms was TURP, UroLift, Rezum, Aquablation, and Greenlight. Google Trends can be an effective tool for evaluating public interest trends in BPH surgery.

Sleeping altitude and sudden cardiac death.

BACKGROUND: Mountain activities characterized by strenuous exercise in a hypoxic setting place unique demands on the body. The mortality rate associated with mountain activities is high, with sudden cardiac death (SCD) representing the most frequent of all nontraumatic deaths. We evaluated the possible effect of acclimatization in reduction of SCD during high-altitude sojourns. METHODS: This was a retrospective cohort study involving all deaths (N = 559) that occurred during mountain activities in Austria from 1985 through 1993. Baseline patient demographics, cardiovascular comorbidities, smoking history, family history of SCD, sleeping altitude, annual mountaineering frequency, and physical activity on the day of SCD were included in a questionnaire previously used in a pilot study. RESULTS: Data from 301 of 599 individuals without prespecified exclusions were available for analysis (79% of eligible cohort). Sudden cardiac deaths happened mostly around noon (29%), and mean altitude at which SCDs occurred was 1,710 ± 501 m. When sleeping altitude was divided into quartiles (<700 m, 700-999 m, 1,000-1,299 m, and >1,299 m), the odds ratio for SCD on the first day at altitude when sleeping below 700 m was 5.7 (95% CI 2.8-11.6) as compared with sleeping above 1,299 m. CONCLUSION: For males >34 years, those with history of coronary artery disease and/or prior infarction, and those unaccustomed to physical activity at altitude, sleeping at moderate altitude before exercising at altitude may reduce the risk of SCD.

Effects of aqueous suspensions of titanium dioxide nanoparticles on Artemia salina: assessment of nanoparticle aggregation, accumulation, and toxicity.

Aquatic stability and impact of titanium dioxide nanoparticles (TiO2 NPs, 10-30 nm) were investigated using Artemia salina. Acute exposure was conducted on nauplii (larvae) and adults in seawater in a concentration range from 10 to 100 mg/L TiO2 NPs for 24 and 96 h. Rapid aggregation occurred in all suspensions of TiO2 NPs to form micrometer size particles. Yet, both nauplii and adults accumulated the aggregates significantly. Average TiO2 content in nauplii ranged from 0.47 to 3.19 and from 1.29 to 4.43 mg/g in 24 and 96 h, respectively. Accumulation in adults was higher ranging from 2.30 to 4.19 and from 4.38 to 6.20 mg/g in 24 and 96 h, respectively. Phase contrast microscopy images revealed that Artemia were unable to excrete the particles. Thus, the TiO2 aggregates filled inside the guts. No significant mortality or toxicity occurred within 24 h at any dose. Lipid peroxidation levels characterized with malondialdehyde concentrations were not statistically different from those of the controls (p > 0.05). These results suggested that suspensions of the TiO2 NPs were nontoxic to Artemia, most likely due to the formation of benign TiO2 aggregates in water. In contrast, both mortality and lipid peroxidation increased in extended exposure to 96 h. Highest mortality occurred in 100 mg/L TiO2 NP suspensions; 18 % for nauplii and 14 % for adults (LC50 > 100 mg/L). These effects were attributed to the particle loading inside the guts leading to oxidative stress as a result of impaired food uptake for a long period of time.

Improved hospital discharge and cost savings with esophageal cooling during left atrial ablation.

BACKGROUND: Left atrial ablation to obtain pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF) is a technologically intensive procedure utilizing innovative and continually improving technology. Changes in the technology utilized for PVI can in turn lead to changes in procedure costs. Because of the proximity of the esophagus to the posterior wall of the left atrium, various technologies have been utilized to protect against thermal injury during ablation. The impact on hospital costs during PVI ablation from utilization of different technologies for esophageal protection during ablation has not previously been evaluated. OBJECTIVE: To compare the costs of active esophageal cooling to luminal esophageal temperature (LET) monitoring during left atrial ablation. METHODS: We performed a time-driven activity-based costing (TDABC) analysis to determine costs for PVI procedures. Published data and literature review were utilized to determine differences in procedure time and same-day discharge rates using different esophageal protection technologies and to determine the cost impacts of same-day discharge versus overnight hospitalization after PVI procedures. The total costs were then compared between cases using active esophageal cooling to those using LET monitoring. RESULTS: The effect of implementing active esophageal cooling was associated with up to a 24.7% reduction in mean total procedure time, and an 18% increase in same-day discharge rate. TDABC analysis identified a $681 reduction in procedure costs associated with the use of active esophageal cooling after including the cost of the esophageal cooling device. Factoring in the 18% increase in same-day discharge resulted in an increased cost savings of $2,135 per procedure. CONCLUSIONS: The use of active esophageal cooling is associated with significant cost-savings when compared to traditional LET monitoring, even after accounting for the additional cost of the cooling device. These savings originate from a per-patient procedural time savings and a per-population improvement in same-day discharge rate.

Relative search popularity of five advanced prostate cancer medications using Google Trends.

BACKGROUND: There are many FDA-approved drugs for advanced prostate cancer (PC), yet public interest in these drugs is not well understood. We compared public interest and state-level predictors of interest in five common oral adjunctive hormonal therapies. METHODS: Google Trends™ was queried for: "Enzalutamide", "Abiraterone Acetate", "Bicalutamide", "Apalutamide", and "Darolutamide" in the United States from January 2004 to November 2022. Data are presented as relative search index (RSI) by month. RSI ranges from 0 to 100 with 100 being peak popularity, 50 being half of the peak popularity, and 0 representing insufficient data to be determined. RESULTS: Several drugs abruptly increased in popularity following FDA approval including abiraterone, enzalutamide, and apalutamide. All drugs decreased in popularity from January 2020 to July 2020, corresponding with the COVID-19 pandemic. In the most recent 5 years, enzalutamide and abiraterone were the most common searched drugs, with bicalutamide a close 3rd place. States that did not expand Medicaid were significantly more likely to have bicalutamide as the top search drug vs. states that expanded Medicaid (p = 0.012). Across all states with data (n = 39), higher bicalutamide RSIs were significantly associated with lower household income (r = 0.385, p = 0.02) and greater percent of uninsured adults (r = 0.426, p = 0.007). This is the first study using Google Trends to compare advanced PC drugs by search popularity. CONCLUSIONS: Despite the emergence of more effective medications, bicalutamide remains relatively popular, particularly in states with lower household income, more uninsured adults, or those that did not expand Medicaid, possibly due to its lower cost.

27-hydroxycholesterol and DNA damage repair: implication in prostate cancer.

Introduction: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects. Methods: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment analysis was done using the GSEA software with hallmark gene sets from MSigDB. Key changes were validated at mRNA and protein levels. Human PC transcriptomes from six datasets were analyzed to determine the correlation between CYP27A1 and DNA repair gene expression signatures. DNA damage was assessed via comet assays. Results: Transcriptome analysis revealed 27HC treatment downregulated Hallmark pathways related to DNA damage repair, decreased expression of FEN1 and RAD51, and induced "BRCAness" by downregulating genes involved in homologous recombination regulation in LNCaP cells. Consistently, we found a correlation between higher CYP27A1 expression (i.e., higher intracellular 27HC) and decreased expression of DNA repair gene signatures in castration-sensitive PC (CSPC) in human PC datasets. However, such correlation was less clear in metastatic castration-resistant PC (mCRPC). 27HC increased expression of DNA damage repair markers in PC cells, notably in AR+ cells, but no consistent effects in AR- cells and decreased expression in non-neoplastic prostate epithelial cells. While testing the clinical implications of this, we noted that 27HC treatment increased DNA damage in LNCaP cells via comet assays. Effects were reversible by adding back cholesterol, but not androgens. Finally, in combination with olaparib, a PARP inhibitor, we showed additive DNA damage effects. Discussion: These results suggest 27HC induces "BRCAness", a functional state thought to increase sensitivity to PARP inhibitors, and leads to increased DNA damage, especially in CSPC. Given the emerging appreciation that defective DNA damage repair can drive PC growth, future studies are needed to test whether 27HC creates a synthetic lethality to PARP inhibitors and DNA damaging agents in CSPC.

Atrioesophageal Fistula Rates Before and After Adoption of Active Esophageal Cooling During Atrial Fibrillation Ablation.

BACKGROUND: Active esophageal cooling reduces the incidence of endoscopically identified severe esophageal lesions during radiofrequency (RF) catheter ablation of the left atrium for the treatment of atrial fibrillation. A formal analysis of the atrioesophageal fistula (AEF) rate with active esophageal cooling has not previously been performed. OBJECTIVES: The authors aimed to compare AEF rates before and after the adoption of active esophageal cooling. METHODS: This institutional review board (IRB)-approved study was a prospective analysis of retrospective data, designed before collecting and analyzing the real-world data. The number of AEFs occurring in equivalent time frames before and after adoption of cooling using a dedicated esophageal cooling device (ensoETM, Attune Medical) were quantified across 25 prespecified hospital systems. AEF rates were then compared using generalized estimating equations robust to cluster correlation. RESULTS: A total of 14,224 patients received active esophageal cooling during RF ablation across the 25 hospital systems, which included a total of 30 separate hospitals. In the time frames before adoption of active cooling, a total of 10,962 patients received primarily luminal esophageal temperature (LET) monitoring during their RF ablations. In the preadoption cohort, a total of 16 AEFs occurred, for an AEF rate of 0.146%, in line with other published estimates for procedures using LET monitoring. In the postadoption cohort, no AEFs were found in the prespecified sites, yielding an AEF rate of 0% (P < 0.0001). CONCLUSIONS: Adoption of active esophageal cooling during RF ablation of the left atrium for the treatment of atrial fibrillation was associated with a significant reduction in AEF rate.

Reduced Procedure Time and Variability with Active Esophageal Cooling During Radiofrequency Ablation for Atrial Fibrillation.

Various methods are utilized during radiofrequency (RF) pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF) to protect the esophagus from inadvertent thermal injury. Active esophageal cooling is increasingly being used over traditional luminal esophageal temperature (LET) monitoring, and each approach may influence procedure times and the variability around those times. The objective of this study is to measure the effects on procedure time and variability in procedure time of two different esophageal protection strategies utilizing advanced informatics techniques to facilitate data extraction. Trained clinical informaticists first performed a contextual inquiry in the catheterization laboratory to determine laboratory workflows and observe the documentation of procedural data within the electronic health record (EHR). These EHR data structures were then identified in the electronic health record reporting database, facilitating data extraction from the EHR. A manual chart review using a REDCap database created for the study was then performed to identify additional data elements, including the type of esophageal protection used. Procedure duration was then compared using summary statistics and standard measures of dispersion. A total of 164 patients underwent radiofrequency PVI over the study timeframe; 63 patients (38%) were treated with LET monitoring, and 101 patients (62%) were treated with active esophageal cooling. The mean procedure time was 176 min (SD of 52 min) in the LET monitoring group compared to 156 min (SD of 40 min) in the esophageal cooling group (P = 0.012). Thus, active esophageal cooling during PVI is associated with reduced procedure time and reduced variation in procedure time when compared to traditional LET monitoring.

Active esophageal cooling during radiofrequency ablation of the left atrium: data review and update.

INTRODUCTION: Radiofrequency (RF) ablation of the left atrium of the heart is increasingly used to treat atrial fibrillation (AF). Unfortunately, inadvertent thermal injury to the esophagus can occur during this procedure, potentially creating an atrioesophageal fistula (AEF) which is 80% fatal. The ensoETM (Attune Medical, Chicago, IL), is an esophageal cooling device that has been shown to reduce thermal injury to the esophagus during RF ablation. AREAS COVERED: This review summarizes growing evidence related to active esophageal cooling during RF ablation for the treatment of AF. The review presents data demonstrating improved outcomes related to patient safety and procedural efficiency and suggests directions for future research. EXPERT OPINION: The use of active esophageal cooling during RF ablation reduces esophageal injury, reduces or eliminates fluoroscopy requirements, reduces procedure duration and post-operative pain, and increases long-term freedom from arrhythmia. These effects in turn increase patient same-day discharge rates, decrease operator cognitive load, and reduce cost. These findings are likely to further accelerate the adoption of active esophageal cooling.

Atrial fibrillation is a condition in which the heart beats irregularly, causing symptoms such as palpitations, dizziness, shortness of breath, and chest pain. Atrial fibrillation increases the risk of stroke, heart failure, dementia, and death. One treatment for atrial fibrillation is a procedure called a catheter ablation. This procedure is minimally invasive and is performed by a specialized cardiologist, called an electrophysiologist. The electrophysiologist, or operator, uses an energy source, such as radiofrequency energy (radio waves), to stop erratic electrical signals from traveling through the heart. One complication of the catheter ablation is an inadvertent injury to the esophagus, the organ that passes food from the mouth to the stomach. If the injury is severe, it may develop into an atrioesophageal fistula, which often results in death. In this review, a new technology is described that helps prevent this type of injury and can provide additional benefits for the patient, operator, and hospital.

New-Onset Atrial Fibrillation in Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Registry.

BACKGROUND: New-onset atrial fibrillation (AF) in patients hospitalized with COVID-19 has been reported and associated with poor clinical outcomes. We aimed to understand the incidence of and outcomes associated with new-onset AF in a diverse and representative US cohort of patients hospitalized with COVID-19. METHODS: We used data from the American Heart Association COVID-19 Cardiovascular Disease Registry. Patients were stratified by the presence versus absence of new-onset AF. The primary and secondary outcomes were in-hospital mortality and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, stroke, cardiogenic shock, and heart failure). The association of new-onset AF and the primary and secondary outcomes was evaluated using Cox proportional-hazards models for the primary time to event analyses. RESULTS: Of the first 30 999 patients from 120 institutions across the United States hospitalized with COVID-19, 27 851 had no history of AF. One thousand five hundred seventeen (5.4%) developed new-onset AF during their index hospitalization. New-onset AF was associated with higher rates of death (45.2% versus 11.9%) and MACE (23.8% versus 6.5%). The unadjusted hazard ratio for mortality was 1.99 (95% CI, 1.81-2.18) and for MACE was 2.23 (95% CI, 1.98-2.53) for patients with versus without new-onset AF. After adjusting for demographics, clinical comorbidities, and severity of disease, the associations with death (hazard ratio, 1.10 [95% CI, 0.99-1.23]) fully attenuated and MACE (hazard ratio, 1.31 [95% CI, 1.14-1.50]) partially attenuated. CONCLUSIONS: New-onset AF was common (5.4%) among patients hospitalized with COVID-19. Almost half of patients with new-onset AF died during their index hospitalization. After multivariable adjustment for comorbidities and disease severity, new-onset AF was not statistically significantly associated with death, suggesting that new-onset AF in these patients may primarily be a marker of other adverse clinical factors rather than an independent driver of mortality. Causality between the MACE composites and AF needs to be further evaluated.

Spironolactone therapy is associated with reduced ventricular tachycardia rate in patients with cardiomyopathy.

INTRODUCTION: Multiple pharmacological therapies currently in prevalent clinical use for cardiac diseases have antifibrotic properties. Spironolactone, a potent antifibrotic agent, is currently used for advanced heart failure. Therapies such as HMG-CoA reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors (ACEi) also have antifibrotic properties. However, the effect of these medications on the ventricular arrhythmia phenotype is currently unknown. Therefore, we set out to define the ventricular arrhythmia rates in patients actively treated with such therapies. METHODS AND RESULTS: We retrospectively evaluated the ventricular tachycardia (VT) rates in patients with structural heart disease actively treated with therapies with antifibrotic properties. VT rates were significantly diminished in patients treated with spironolactone (158 ± 26 beats per minute [bpm], n = 21) compared to patients on no medications (205 ± 22 bpm, n = 13) or those who were on similar heart-failure therapies but not on spironolactone (186 ± 32 bpm, n = 82). In addition, we observed that VT rates showed a significant trend toward lower rates in patients receiving either statins or ACEi, compared to patients on no medical therapy. In multivariate analysis, spironolactone therapy was identified as the single most significant variable for reduced VT rate. CONCLUSION: Use of spironolactone in patients with heart failure is associated with reduced VT rate. Similar but less-significant reductions in VT rates were observed with use of other pharmacological agents with antifibrotic properties, such as statins and ACEi. Our findings, at least in part, could account for reduction in sudden cardiac death rates documented with use of these therapies.

Preventing shoulder pain after cardiac rhythm management device implantation: a randomized, controlled study.

INTRODUCTION: Shoulder pain and disability ipsilateral to the implant site is a common complication of cardiac rhythm device implantation, yet very little has been published about this morbidity. We designed a study to assess the potential benefit of a simple exercise protocol in preventing shoulder pain postoperatively. METHODS AND RESULTS: Patients undergoing subcutaneous device implantation were randomized to one of two groups. The control group received standard instructions, whereas the exercise group was instructed on specific exercises aimed at strengthening or stretching the shoulder girdle, to be completed 3 days per week. Groups were postoperatively monitored for the development of shoulder discomfort and shoulder impingement by using physical examination and disability questionnaires. At 1 month, seven of 21 control patients reported developing shoulder pain or discomfort compared to one of 23 in the exercise group (P = 0.02). At 6 months, four of 23 control patients still reported worsening shoulder symptoms, compared to none in the exercise group (P = 0.11). In the control group, five of 19 patients developed a positive impingement test at 1 month, versus none in the exercise group (P = 0.01). Scores for the questionnaires designed to assess shoulder pain and dysfunction were worse in the control group. There were no activity-related complications in either group. CONCLUSION: Shoulder pain and disability occurs often following cardiac rhythm management device implantation. A simple exercise program aimed at strengthening the shoulder girdle is effective at preventing this complication.