Efficacy of Aspirin for primary prevention among adults with high-risk type 2 diabetes in the ACCORD trial.

AIM: To assess the  of aspirin use for primary prevention of cardiovascular disease (CVD) with incident atherosclerotic CVD and mortality in high-risk type 2 diabetes. METHODS: In this post hoc analysis, we included participants in the ACCORD trial without CVD at baseline. The association between aspirin use and the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular [CV] death) and all-cause mortality was evaluated using Cox proportional hazard analysis adjusting for demographics, CV risk factors and comorbidities. RESULTS: Eligible participants (n = 6330) were aged 62.8 ± 5.9 years at baseline, 43.8% of the participants were female, and 3026 (47.8%) used aspirin. Over a median (interquartile range) follow-up of 4.9 (4.1-5.7) years, the number (%) of primary outcome and all-cause mortality events in those who used aspirin (vs. those who did not), was 196 (6.5) versus 229 (6.9) and 146 (4.8) versus 147 (4.5), respectively. The adjusted hazard ratios (95% confidence interval) associated with aspirin use for the primary outcome and all-cause mortality were 0.94 (0.77-1.14) and 1.08 (0.85-1.36), respectively. CONCLUSION: In high-risk individuals with type 2 diabetes, the use of aspirin for primary prevention was not associated with a decreased risk of incident CVD or all-cause mortality.

Mechanisms of action behind the protective effects of proactive esophageal cooling during radiofrequency catheter ablation in the left atrium.

Proactive esophageal cooling for the purpose of reducing the likelihood of ablation-related esophageal injury resulting from radiofrequency (RF) cardiac ablation procedures is increasingly being used and has been Food and Drug Administration cleared as a protective strategy during left atrial RF ablation for the treatment of atrial fibrillation. In this review, we examine the evidence supporting the use of proactive esophageal cooling and the potential mechanisms of action that reduce the likelihood of atrioesophageal fistula (AEF) formation. Although the pathophysiology behind AEF formation after thermal injury from RF ablation is not well studied, a robust literature on fistula formation in other conditions (eg, Crohn disease, cancer, and trauma) exists and the relationship to AEF formation is investigated in this review. Likewise, we examine the abundant data in the surgical literature on burn and thermal injury progression as well as the acute and chronic mitigating effects of cooling. We discuss the relationship of these data and maladaptive healing mechanisms to the well-recognized postablation pathophysiological effects after RF ablation. Finally, we review additional important considerations such as patient selection, clinical workflow, and implementation strategies for proactive esophageal cooling.

Association between blood pressure levels and premature atrial contractions in patients with hypertension.

BACKGROUND: High blood pressure (BP) induces left atrial structural and functional remodeling that increases susceptibility to atrial arrhythmia. We hypothesized that lower systolic BP (SBP) levels are associated with a lower prevalence of premature atrial contractions (PACs) in patients with hypertension. METHODS: This analysis included 4,697 participants (mean age 62±13.1 years, 50% women, 25.6% blacks) with hypertension from the Third National Health and Nutrition Examination Survey who did not have a prior history of cardiovascular disease (CVD). Multivariable logistic regression was used to examine the cross-sectional association between SBP and prevalence of PACs ascertained from 12-lead resting electrocardiograms. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality. RESULTS: Approximately 1.6% (n=74) of participants had baseline PACs. Patients with SBP ≤140 mmHg had a lower prevalence of PACs than those with SBP ≥140 mmHg (1.1% vs. 1.9%, p-value=0.01). In a multivariable logistic regression model, each 10 mmHg decrease in SBP was associated with a 12% lower odds of PACs (OR (95%CI): 0.88 (0.77-0.99)). During 14 years of follow-up, 645 CVD deaths occurred. In a multivariable-adjusted Cox model, presence of PACs was associated with a 78% increased risk of CVD mortality (HR (95%CI): 1.78 (1.23-2.60)). CONCLUSIONS: In patients with hypertension, lower SBP levels are associated with a lower prevalence of PACs, and presence of PACs is associated with a higher risk of CVD mortality risk. These findings highlight the potential role of BP lowering in the management of cardiac arrhythmias.

Relationship Between Sarcopenia and Intensive Blood Pressure Control Efficacy and Safety: A Secondary Analysis of SPRINT.

BACKGROUND: Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. RESULTS: Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. CONCLUSIONS: Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Role of dofetilide in patients with ventricular arrhythmias.

BACKGROUND OR PURPOSE: To assess effectiveness of dofetilide in reducing the burden of ventricular arrhythmias (VAs). BACKGROUND: Prior small sample studies show that dofetilide has benefit in reducing VA. However, large sample investigations with long-term follow-up are lacking. METHODS: Two hundred seventeen consecutive patients admitted between January 2015 and December 2021 for dofetilide initiation for control of VA were assessed. Dofetilide was successfully started in 176 patients (81%) and had to be discontinued in the remaining 41 patients (19%). Dofetilide was initiated for control of ventricular tachycardia (VT) in 136 patients (77%), whereas 40 (23%) patients were initiated on dofetilide for reducing the burden of premature ventricular complexes (PVCs). RESULTS: The mean follow-up was 24 ± 7 months. In total, among the 136 VT patients, 33 (24%) died, 11 (8%) received a left ventricular assist device (LVAD), and 3 (2%) received a heart transplant during follow-up. Dofetilide was discontinued in 117 (86%) patients due to lack of sustained effectiveness during follow-up. Dofetilide use was associated with similar odds of the composite outcome of all-cause mortality/LVAD/heart transplant (OR: 0.97, 0.55-4.23) in patients with ischemic cardiomyopathy (ICM) compared to those with non-ischemic cardiomyopathy (NICM). Dofetilide did not reduce PVC burden during follow-up in the 40 patients with PVCs (mean baseline PVC burden: 15%, at 1-year follow-up: 14%). CONCLUSIONS: Dofetilide use was less effective in reducing VA burden in our cohort of patients. Randomized controlled studies are needed to confirm our findings.

The effects of binge drinking on attention in young adults.

Introduction: Alcohol binge drinking is highly prevalent among young adults. While research has established the neurotoxic effects of general alcohol consumption, binge drinking presents unique deleterious effects on the brain through the acute intoxication and withdrawal cycle. The detrimental impacts of binge drinking have been reported across a broad range of cognitive abilities in young adults, however, the research regarding its relationship to attention is mixed. This study investigates the relationship between binge drinking and attention performance in young adults. Moreover, there is evidence to suggest that males and females are uniquely impacted by the neurotoxic effects of binge drinking, so the present study tests the moderating role of sex, as well as the influence of earlier age of binge drinking onset. Methods: One-hundred and five university students were recruited for the study. After collecting socio-demographic, and alcohol use information, participants completed four cognitive tasks designed to measure the three attention networks according to the Attention Network Theory; alerting, orienting, and executive control. Linear hierarchical regressions were used to predict performance with binge drinking score, sex and age of first binge drinking session as predictors. Results: Binge drinking, sex, and age of first binge drinking session did not predict attention impairment, nor did sex moderate the relationship, at least in the selected cognitive tasks. The tasks used to measure attention did not relate in the expected manner. Discussion: While there were no differences in attention performance between those who binge drink and controls in this study, the relationship between binge drinking and attention impairments in young adults may be more nuanced and future research directions are suggested. Theoretical and practical implications of these findings are discussed.

Association between weight variability, weight change and clinical outcomes in hypertension.

Objective: The effect of body weight variability (BWV) and body weight change (BWC) in high-risk individuals with hypertension, but without diabetes mellitus (DM) remains unclear. We examined the effect of BWV and BWC on the primary outcome [the composite of myocardial infarction (MI), other acute coronary syndromes, stroke, acute decompensated heart failure (HF), or cardiovascular (CV) death] and all-cause mortality in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: In this post-hoc analysis, we used multivariate Cox regression models to examine the risk associated with BWV and BWC for the primary outcome in SPRINT. BWV was defined as the intra-individual average successive variability (ASV). BWC was defined as baseline weight minus final weight. Results: A total of 8714 SPRINT participants (mean age 67.8 ± 9.4 years, 35.1 % women, 58.9 % Whites) with available data on body weight were included. The median follow-up was about 3.9 years (IQR, 3.3-4.4). In multivariable-adjusted Cox models, each 1 unit standard deviation (SD) of BWV was significantly associated with a higher risk for the primary outcome, all-cause mortality, HF, MI, and stroke [HR(95 % CI)]: 1.13 (1.07-1.19; p < 0.0001), 1.22 (1.14-1.30; p < 0.0001), 1.16 (1.07-1.26; p < 0.001), 1.10 (1.00-1.20; p = 0.047), and 1.15 (1.05-1.27; p = 0.005), respectively. Similarly, each 1 unit SD of BWC was significantly associated with a higher risk of the primary outcome, all-cause mortality, MI, and HF: 1.11(1.02-1.21; p = 0.017), 1.44 (1.26-1.65; p < 0.0001), 1.16 (1.01-1.32; p = 0.041) and 1.19 (1.02-1.40; p = 0.031) respectively. However, there was no significant association with CV death (for both BWV and BWC) or stroke (BWC). Conclusion: In high-risk hypertension, BWV and BWC were both associated with higher risk of the primary outcome and all-cause mortality. These results further stress the clinical importance of sustained weight loss and minimizing fluctuations in weight in hypertension.

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.

Association of silent myocardial infarction on electrocardiogram and coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. OBJECTIVE: Characterize the relationship between SMI on ECG and CAC. METHODS: Eligible participants from the Multi-Ethnic Study of Atherosclerosis study had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. RESULTS: Among 6705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0-261.7] vs. 0 [0-81.5]; p < .0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48-3.20, p < .0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06-2.16, p = .02). CONCLUSION: An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.

Association between physical activity and clinical outcomes in high-risk hypertension: Post-hoc analysis of SPRINT.

Objective: Engaging in physical activity (PA) is recommended to reduce the risk of morbidity and mortality in patients with hypertension. However, the association between PA and clinical outcomes in individuals with high-risk hypertension is understudied. We examined the relationship between PA and clinical outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT investigated the benefit of intensive (vs. standard) blood pressure treatment in patients with high-risk hypertension. Methods: Baseline data on PA was self-reported. Vigorous-intensity PA (VPA) was categorized into 2 groups based on frequency of "Rarely or Never" and 1 or more sessions/month. Moderate-intensity PA (MPA) was also categorized into 2 groups based on average duration/day of <15 min and 15 or more minutes. Using multivariable Cox regression, we estimated the associations between PA the primary outcome which was a composite of cardiovascular events, and all-cause mortality. Results: A total of 8,320 (age 67.8 ± 9.3, 34.9% women) of SPRINT participants with data on PA were included. During a median follow-up of 3.8 years, 619 primary outcome, and 419 all-cause mortality events occurred. Compared to not engaging in VPA, the risk of the primary outcome, myocardial infarction, and all-cause mortality (HR 95% CIs) associated with VPA of ≥1sessions/month was 0.79(0.65-0.94; p=0.009), 0.70(0.52-0.93; p=0.014) and 0.75(0.60-0.94; p=0.011), respectively. Similarly, the risk of the primary outcome and all-cause mortality (HR 95% CI) associated with engaging in MPA for ≥15 min/day, relative to <15 min/day was 0.76(0.63-0.93; p=0.008) and 0.80(0.62-1.02; p=0.066), respectively. Conclusion: Among individuals with hypertension from the SPRINT study, VPA and MPA at a threshold of ≥1sessions/month and MPA of ≥15 min/day respectively, were both associated with a lower risk for cardiovascular events, and VPA was also associated with a reduced risk for all-cause mortality. Further studies are required to identify the optimal volume and intensity of PA in high-risk hypertension.

A comparative study of the two leadless pacemakers in clinical practice.

INTRODUCTION: AVEIR-VR leadless pacemaker (LP) was recently approved for clinical use. Although trial data were promising, post-approval real world data with regard to its effectiveness and safety is lacking. To report our early experience with AVEIR-VR LP with regard to its effectiveness and safety and compare it with MICRA-VR. METHODS: The first 25 patients to undergo AVEIR-VR implant at our institution between June and November 2022, were compared to 25 age- and sex-matched patients who received MICRA-VR implants. RESULTS: In both groups, mean age was 73 years and 48% were women. LP implant was successful in 100% of patients in both groups. Single attempt deployment was achieved in 80% of AVEIR-VR and 60% of MICRA-VR recipients (p = 0.07). Fluoroscopy, implant, and procedure times were numerically longer in the AVEIR-VR group compared to MICRA-VR group (p > 0.05). No significant periprocedural complications were noted in both groups. Incidence of ventricular arrhythmias were higher in the AVEIR-VR group (20%) compared to the MICRA-VR group (0%) (p = 0.043). At 2 and 8 weeks follow-up, device parameters remained stable in both groups with no device dislodgements. The estimated battery life at 8 weeks was significantly longer in the AVEIR-VR group (15 years) compared to the MICRA-VR group (8 years) (p = 0.047). With 3-4 AVEIR-VR implants, the learning curve for successful implantation reached a steady state. CONCLUSION: Our initial experience with AVEIR-VR show that it has comparable effectiveness and safety to MICRA-VR. Larger sample studies are needed to confirm our findings.

Spatial transcriptomic analysis of Sonic hedgehog medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition.

BACKGROUND: Medulloblastoma (MB) is a malignant tumour of the cerebellum which can be classified into four major subgroups based on gene expression and genomic features. Single-cell transcriptome studies have defined the cellular states underlying each MB subgroup; however, the spatial organisation of these diverse cell states and how this impacts response to therapy remains to be determined. METHODS: Here, we used spatially resolved transcriptomics to define the cellular diversity within a sonic hedgehog (SHH) patient-derived model of MB and show that cells specific to a transcriptional state or spatial location are pivotal for CDK4/6 inhibitor, Palbociclib, treatment response. We integrated spatial gene expression with histological annotation and single-cell gene expression data from MB, developing an analysis strategy to spatially map cell type responses within the hybrid system of human and mouse cells and their interface within an intact brain tumour section. RESULTS: We distinguish neoplastic and non-neoplastic cells within tumours and from the surrounding cerebellar tissue, further refining pathological annotation. We identify a regional response to Palbociclib, with reduced proliferation and induced neuronal differentiation in both treated tumours. Additionally, we resolve at a cellular resolution a distinct tumour interface where the tumour contacts neighbouring mouse brain tissue consisting of abundant astrocytes and microglia and continues to proliferate despite Palbociclib treatment. CONCLUSIONS: Our data highlight the power of using spatial transcriptomics to characterise the response of a tumour to a targeted therapy and provide further insights into the molecular and cellular basis underlying the response and resistance to CDK4/6 inhibitors in SHH MB.

Anatomical location of leadless pacemaker and the risk of pacing-induced cardiomyopathy.

BACKGROUND: It is unclear if the location of implantation of the leadless pacemaker (LP) makes a difference in the incidence of pacing-induced cardiomyopathy (PICM). AIM: The aim of this study was to compare the incidence of PICM based on the location of implantation of LP. METHODS: A total of 358 consecutive patients [women: 171 (48%), mean age: 73 ± 15 years] with left ventricular ejection fraction (EF) > 50%, who received an LP (Micra) between January 2017 and June 2022, formed the study cohort. Micra-AV and Micra-VR were implanted in 122 (34%) and 236 (66%) patients, respectively. Fluoroscopically, the location of implantation of LP in the interventricular septum (IS) was divided into two equal halves (apex/apical septum [AS] and mid/high septum [HS]). During follow-up, PICM was defined as an EF drop of ≥10%. RESULTS: LP was implanted in 109 (34%) and 249 (66%) patients at AS and HS locations, respectively. During a mean 18 ± 8 months follow-up, 28 patients (7.8%) developed PICM. Among the 249 patients with HS placement of LP, 10 (4%) developed PICM, whereas among the 109 patients with AS placement of LP, 18 (16.5%) developed PICM (p = .002). AS location was associated with a higher risk of PICM compared to HS locations (adjusted hazard ratio: 4.42, p < .001). CONCLUSION: AS location of LP was associated with a higher risk of PICM compared to HS placement. Larger randomized studies are needed to confirm our findings.

A novel ELP1 mutation impairs the function of the Elongator complex and causes a severe neurodevelopmental phenotype.

BACKGROUND: Neurodevelopmental disorders (NDDs) are heterogeneous, debilitating conditions that include motor and cognitive disability and social deficits. The genetic factors underlying the complex phenotype of NDDs remain to be elucidated. Accumulating evidence suggest that the Elongator complex plays a role in NDDs, given that patient-derived mutations in its ELP2, ELP3, ELP4 and ELP6 subunits have been associated with these disorders. Pathogenic variants in its largest subunit ELP1 have been previously found in familial dysautonomia and medulloblastoma, with no link to NDDs affecting primarily the central nervous system. METHODS: Clinical investigation included patient history and physical, neurological and magnetic resonance imaging (MRI) examination. A novel homozygous likely pathogenic ELP1 variant was identified by whole-genome sequencing. Functional studies included in silico analysis of the mutated ELP1 in the context of the holo-complex, production and purification of the ELP1 harbouring the identified mutation and in vitro analyses using microscale thermophoresis for tRNA binding assay and acetyl-CoA hydrolysis assay. Patient fibroblasts were harvested for tRNA modification analysis using HPLC coupled to mass spectrometry. RESULTS: We report a novel missense mutation in the ELP1 identified in two siblings with intellectual disability and global developmental delay. We show that the mutation perturbs the ability of ELP123 to bind tRNAs and compromises the function of the Elongator in vitro and in human cells. CONCLUSION: Our study expands the mutational spectrum of ELP1 and its association with different neurodevelopmental conditions and provides a specific target for genetic counselling.

Look before you place: A bizarre ECG artifact due to lead placement.

The Electrocardiogram (ECG) is a readily available non-invasive test used in the evaluation of a patient with angina. ECG artifacts are common and stem from a number of different reasons including lead placement and must be identified to appropriately manage patients. We present the case of an elderly patient for whom an ECG was performed to evaluate chest pain showing an abnormal waveform concerning for an ST elevation myocardial infarction (STEMI). Closer inspection of the ECG revealed a characteristic pattern documented in the literature known as Aslanger's Sign seen when an ECG lead is placed over an artery.

Evaluation of lead-based echodensities on transesophageal echocardiogram in patients with cardiac implantable electronic devices.

INTRODUCTION: Transesophageal echocardiography (TEE) is recommended to rule out endocarditis in patients with cardiac implantable electronic devices (CIED). A lead-based echodensity (LBE), however, is often found on TEE in patients with a CIED and may not represent an infection. We sought to evaluate the predictors, characteristics, and clinical significance of LBEs seen on TEE in patients with a CIED. METHODS: Patients with a CIED were retrospectively identified from a database using International Classification of Diseases (ICD)-9/ICD-10 codes and were cross-matched with Current Procedural Terminology codes for a TEE. Clinical and follow-up data were collected. A blinded echo board-certified cardiologist reviewed all TEEs. RESULTS: Out of the 231 patients in the cohort, 191 had TEE performed for a noninfection-related indication while 40 TEEs were part of an endocarditis workup. A total of 50 LBEs were identified, and a majority were in the noninfection cohort. Systemic anticoagulant use in the noninfection cohort was associated with a decreased odds of having LBE on TEE (odds ratio [OR] of 0.23 [95% confidence interval [CI]: 0.06-0.60, p = .003]). Lead dwell time in the noninfection cohort was associated with an increased odds of having LBE on TEE (OR 1.21 (95% CI: 1.04-1.39, p = .009]). CONCLUSION: In our cohort of patients who had TEE for noninfection indications we found that systemic anticoagulant use is associated with fewer LBEs on TEEs, suggesting possible thrombin fibrin composition of LBE.

Comparison of Bolus Dosing of Methohexital and Propofol in Elective Direct Current Cardioversion.

Background Methohexital and propofol can both be used as sedation for direct current cardioversion (DCCV). However, there are limited data comparing these medications in this setting. We hypothesized that patients receiving methohexital for elective DCCV would be sedated more quickly, recover from sedation faster, and experience less adverse effects. Methods and Results This was a prospective, blinded randomized controlled trial conducted at a single academic medical center. Eligible participants were randomly assigned to receive either methohexital (0.5 mg/kg) or propofol (0.8 mg/kg) as a bolus for elective DCCV. The times from bolus of the medication to achieving a Ramsay Sedation Scale score of 5 to 6, first shock, eyes opening on command, and when the patient could state their age and name were obtained. The need for additional medication dosing, airway intervention, vital signs, and medication side effects were also recorded. Seventy patients who were randomized to receive methohexital (n=37) or propofol (n=33) were included for analysis. The average doses of methohexital and propofol were 0.51 mg/kg and 0.84 mg/kg, respectively. There were no significant differences between methohexital and propofol in the time from end of injection to loss of conscious (1.4±1.8 versus 1.1±0.5 minutes; P=0.33) or the time to first shock (1.7±1.9 versus 1.4±0.5 minutes; P=0.31). Time intervals were significantly lower for methohexital compared with propofol in the time to eyes opening on command (5.1±2.5 versus 7.8±3.7 minutes; P=0.0005) as well as at the time to the ability to answer simple questions of age and name (6.0±2.6 versus 8.6±4.0 minutes; P=0.001). The methohexital group experienced less hypotension (8.1% versus 42.4%; P<0.001) and less hypoxemia (0.0% versus 15.2%; P=0.005), had lower need for jaw thrust/chin lift (16.2% versus 42.4%; P=0.015), and had less pain on injection compared with propofol using the visual analog scale (7.2±9.7 versus 22.4±28.1; P=0.003). Conclusions In this model of fixed bolus dosing, methohexital was associated with faster recovery, more stable hemodynamics, and less hypoxemia after elective DCCV compared with propofol. It can be considered as a preferred agent for sedation for DCCV. Registration URL: https://www.clinicaltrials.gov/ct; Unique identifier: NCT04187196.