Management of Atrial Fibrillation in the Emergency Department.

PURPOSE OF REVIEW: Atrial fibrillation (AF) is the most common arrhythmia in adults and is responsible for 600,000 emergency department (ED) visits each year in the USA. Over 60% of these patients are admitted to inpatient units. The prevalence of AF is increasing, resulting in higher numbers of AF-related ED visits and inpatient admissions. These trends underscore the need for improvements in the efficiency of AF management in the ED. RECENT FINDINGS: Several treatment protocols have been developed to address challenges associated with AF management in the ED, including: initiation of oral anticoagulant (OAC) therapy, cardioversion, and arranging for outpatient follow-up. Studies of these protocols have demonstrated that they can be utilized safely and effectively. Published treatment protocols for AF in the ED have been shown to reduce unnecessary hospital admissions and improve adherence to guideline-directed OAC therapy. Widespread adoption of AF treatment protocols could improve patient outcomes and reduce the costs associated with inpatient AF treatment.

Novel automated point collection software facilitates rapid, high-density electroanatomical mapping with multiple catheter types.

INTRODUCTION: Manual, point-by-point electroanatomical mapping requires the operator to directly evaluate each point during map construction. Consequently, point collection can be a slow process. An automated 3D mapping system was developed with the goal of improving key mapping metrics, including map completion time and point density. METHODS: Automated 3D mapping software that includes morphology and cycle length discrimination functions for surface and intracardiac electrograms was developed. In five swine, electroanatomical maps (EAMs) of all four cardiac chambers were generated in sinus rhythm. Four catheters were used: two different four-pole ablation catheters, a 20-pole circular catheter, and a 64-pole basket catheter. Automated and manual 3D mapping were compared for 12 different catheter-chamber combinations (paired sets of 10 maps for most combinations, for a total of 156 maps). RESULTS: Automated 3D mapping produced more than twofold increase in the number of points per map, as compared with manual 3D mapping (P ≤0.007 for all catheter-chamber combinations tested). Automated 3D mapping also reduced map completion time by an average of 29% (P < 0.05 for all comparisons). The amount of manual editing of the maps acquired with automated 3D mapping was minimal. CONCLUSION: Automated 3D mapping with the open-platform mapping software described in this study is significantly faster than manual, point-by-point 3D mapping. This resulted in shorter mapping time and higher point density. The morphology discrimination functions effectively excluded ectopic beats during mapping in sinus rhythm and allowed for rapid mapping of intermittent ventricular ectopic beats.

Safety and efficacy of delivering high-power short-duration radiofrequency ablation lesions utilizing a novel temperature sensing technology.

Aims: Delivery of high-power short-duration radiofrequency (RF) ablation lesions is not commonly used, in part because conventional thermocouple (TC) technology underestimates tissue temperature, increasing the risk of steam pop, and thrombus formation. We aimed to test whether utilization of an ablation catheter equipped with a highly accurate novel TC technology could facilitate safe and effective delivery of high-power RF lesions. Methods and results: Adult male Yorkshire swine were used for the study. High-power short-duration ablations (10-s total; 90 W for 4 s followed by 50 W for 6 s) were delivered using an irrigated force sensing catheter, equipped with six miniature TC sensors embedded in the tip electrode shell. Power modulation was automatically performed when the temperature reached 65°C. Ablation parameters were recorded and histopathological analysis was performed to assess lesion formation. One hundred and fourteen RF applications, delivered using the study ablation protocol in the ventricles of eight swine [53 in the right ventricle (RV), 61 in the left ventricle (LV)], were analysed. Average power delivered was 55.4 ± 5.3 W and none of the ablations resulted in a steam pop. Fourteen out of the 114 (12.3%) lesions were transmural. The mean lesion depth was 3.9 ± 1.1 mm for the 100 non-transmural lesions. Similar ablation parameters resulted in bigger impedance drop (11.6 Ω vs. 9.1 Ω, P = 0.009) and deeper lesions in the LV compared with the RV (4.3 ± 1.2 mm vs. 3.3 ± 0.8 mm, P < 0.001). Conclusion: Delivery of high-power short-duration RF energy applications, facilitated by a novel ablation catheter system equipped with advanced TC technology, is feasible, safe, and results in the formation of effective ablation lesions.

Single-scan rest/stress imaging: validation in a porcine model with 18F-Flurpiridaz.

PURPOSE: 18F-labeled myocardial flow agents are becoming available for clinical application but the ∼2 hour half-life of 18F complicates their clinical application for rest-stress measurements. The goal of this work is to evaluate in a pig model a single-scan method which provides quantitative rest-stress blood flow in less than 15 minutes. METHODS: Single-scan rest-stress measurements were made using 18F-Flurpiridaz. Nine scans were performed in healthy pigs and seven scans were performed in injured pigs. A two-injection, single-scan protocol was used in which an adenosine infusion was started 4 minutes after the first injection of 18F-Flurpiridaz and followed either 3 or 6 minutes later by a second radiotracer injection. In two pigs, microsphere flow measurements were made at rest and during stress. Dynamic images were reoriented into the short axis view, and regions of interest (ROIs) for the 17 myocardial segments were defined in bull's eye fashion. PET data were fitted with MGH2, a kinetic model with time varying kinetic parameters, in which blood flow changes abruptly with the introduction of adenosine. Rest and stress myocardial blood flow (MBF) were estimated simultaneously. RESULTS: The first 12-14 minutes of rest-stress PET data were fitted in detail by the MGH2 model, yielding MBF measurement with a mean precision of 0.035 ml/min/cc. Mean myocardial blood flow across pigs was 0.61 ± 0.11 mL/min/cc at rest and 1.06 ± 0.19 mL/min/cc at stress in healthy pigs and 0.36 ± 0.20 mL/min/cc at rest and 0.62 ± 0.24 mL/min/cc at stress in the ischemic area. Good agreement was obtained with microsphere flow measurement (slope = 1.061 ± 0.017, intercept = 0.051 ± 0.017, mean difference 0.096 ± 0.18 ml/min/cc). CONCLUSION: Accurate rest and stress blood flow estimation can be obtained in less than 15 min of PET acquisition. The method is practical and easy to implement suggesting the possibility of clinical translation.

Increased perforation risk with an MRI-conditional pacing lead: a single-center study.

BACKGROUND: Magnetic resonance imaging (MRI) has been considered contraindicated in patients with cardiac pacemakers (PPMs). Recently, Medtronic (MDT) MRI SureScan PPM (Medtronic Inc., Minneapolis, MN, USA) and leads were introduced into clinical practice in the United States of America. OBJECTIVE: To compare MDT CapSureFix 5086 MRI SureScan lead-associated perforation and dislodgement rates with MDT non-MRI SureScan active fixation leads. METHODS: We retrospectively analyzed the records of all patients implanted with MDT CapSureFix 5086 MRI SureScan leads as well as all patients implanted with MDT 4076 and 5076 leads at our institution from April 2011 to April 2014. RESULTS: Four of 72 patients implanted with MDT CapSureFix 5086 MRI SureScan leads (5.5%) had evidence of lead perforation, necessitating pericardiocentesis in three cases and lead revision in one case. Three of the four perforations were delayed perforations, presenting more than 3 weeks postimplant. Two patients implanted with MDT CapSureFix 5086 MRI SureScan leads (2.8%) had lead dislodgement. Of 420 patients implanted with MDT non-MRI SureScan leads, there were two perforations (0.47%) and four dislodgements (0.9%). There were significantly increased lead perforations associated with MDT CapSureFix 5086 MRI SureScan leads (P = 0.005) and a nonsignificant trend toward increased dislodgements (P = 0.18) when compared with MDT non-MRI SureScan leads. CONCLUSION: In contradiction to prior studies, this retrospective study suggests an increased perforation rate with MDT CapSureFix 5086 MRI SureScan leads. Most perforations were delayed perforations, presenting more than 3 weeks postimplant. Higher volume prospective studies with longer follow-up are needed to confirm our findings.

Towards regenerative therapy for cardiac disease.

Development of regenerative therapeutic strategies to reverse the progression of advanced heart failure is one of the most urgent clinical needs of this century. Insights gained from clinical trials of adult stem cells, together with fundamental scientific advances in cardiac stem cell and regenerative biology, are beginning to yield potential new targets and strategies for regenerative therapies. Of particular importance are new scientific discoveries related to intrinsic cardiac regeneration, renewal factors that can trigger regeneration, and tissue-engineering technology, which are beginning to change the way investigators view the scientific and clinical position of cardiovascular regenerative therapy.

Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species.

Mammalian preimplantation embryonic development (PED) is thought to be governed by highly conserved processes. While it had been suggested that some plasticity of conserved signaling networks exists among different mammalian species, it was not known to what extent modulation of the genomes and the regulatory proteins could "rewire" the gene regulatory networks (GRN) that control PED. We therefore generated global transcriptional profiles from three mammalian species (human, mouse, and bovine) at representative stages of PED, including: zygote, two-cell, four-cell, eight-cell, 16-cell, morula and blastocyst. Coexpression network analysis suggested that 40.2% orthologous gene triplets exhibited different expression patterns among these species. Combining the expression data with genomic sequences and the ChIP-seq data of 16 transcription regulators, we observed two classes of genomic changes that contributed to interspecies expression difference, including single nucleotide mutations leading to turnover of transcription factor binding sites, and insertion of cis-regulatory modules (CRMs) by transposons. About 10% of transposons are estimated to carry CRMs, which may drive species-specific gene expression. The two classes of genomic changes act in concert to drive mouse-specific expression of MTF2, which links POU5F1/NANOG to NOTCH signaling. We reconstructed the transition of the GRN structures as a function of time during PED. A comparison of the GRN transition processes among the three species suggested that in the bovine system, POU5F1's interacting partner SOX2 may be replaced by HMGB1 (a TF sharing the same DNA binding domain with SOX2), resulting in rewiring of GRN by a trans change.

Outcomes of Patients With Takotsubo Syndrome Compared With Type 1 and Type 2 Myocardial Infarction.

Background Takotsubo syndrome (TS) and myocardial infarction (MI) share similar clinical and laboratory characteristics but have important differences in causes, demographics, management, and outcomes. Methods and Results In this observational study, the National Inpatient Sample and National Readmission Database were used to identify patients admitted with TS, type 1 MI, or type 2 MI in the United States between October 1, 2017, and December 31, 2019. We compared patients hospitalized with TS, type 1 MI, and type 2 MI with respect to key features and outcomes. Over the 27-month study period, 2 035 055 patients with type 1 MI, 639 075 patients with type 2 MI, and 43 335 patients with TS were identified. Cardiac arrest, ventricular fibrillation, and ventricular tachycardia were more prevalent in type 1 MI (4.02%, 3.2%, and 7.2%, respectively) compared with both type 2 MI (2.8%, 0.8%, and 5.4% respectively) and TS (2.7%, 1.8%, and 5.3%, respectively). Risk of mortality was lower in TS compared with both type 1 MI (3.3% versus 7.9%; adjusted odds ratio [OR], 0.3; P<0.001) and type 2 MI (3.3% versus 8.2%; adjusted OR, 0.3; P<0.001). Mortality rate (OR, 1.2; P<0.001) and cardiac-cause 30-day readmission rate (adjusted OR, 1.7; P<0.001) were higher in type 1 MI than in type 2 MI. Conclusions Patients with type 1 MI had the highest rates of in-hospital mortality and cardiac-cause 30-day readmission. Risk of all-cause 30-day readmission was highest in patients with type 2 MI. The risk of ventricular arrhythmias in patients with TS is lower than in patients with type 1 MI but higher than in patients with type 2 MI.

Safe and effective delivery of high-power, short-duration radiofrequency ablation lesions with a flexible-tip ablation catheter.

Background: High-power, short-duration (HPSD) radiofrequency ablation (RFA) may reduce ablation time. Concerns that catheter-mounted thermocouples (TCs) can underestimate tissue temperature, resulting in elevated risk of steam pop formation, potentially limit widespread adoption of HPSD ablation. Objective: The purpose of this study was to compare the safety and efficacy of HPSD and low-power, long-duration (LPLD) RFA in the context of pulmonary vein isolation (PVI). Methods: An open-irrigated ablation catheter with a contact force sensor and a flexible-tip electrode containing a TC at its distal end (TactiFlexTM Ablation Catheter, Sensor EnabledTM, Abbott) was used to isolate the left pulmonary veins (PVs) in 12 canines with HPSD RFA (50 W for 10 seconds) and LPLD RFA (30 W for a maximum of 60 seconds). PVI was assessed at 30 minutes and 28 ± 3 days postablation. Computed tomographic scans were performed to assess PV stenosis after RFA. Lesions were evaluated with histopathology. Results: A total of 545 ablations were delivered: 252 with LPLD (0 steam pops) and 293 with HPSD RFA (2 steam pops) (P = .501). Ablation time required to achieve PVI was >3-fold shorter for HPSD than for LPLD RFA (P = .001). All 24 PVs were isolated 30 minutes after ablation, with 12/12 LPLD-ablated and 11/12 HPSD-ablated PVs still isolated at follow-up. Histopathology revealed transmural ablations for HPSD and LPLD RFA. No major adverse events occurred. Conclusion: An investigational ablation catheter effectively delivered RFA lesions. Ablation time required to achieve PVI with HPSD with this catheter was >3-fold shorter than with LPLD RFA.

Human embryonic stem cells: emerging technologies and practical applications.

Human embryonic stem cells possess the unique ability to differentiate into any adult cell type. Recent advances in the understanding of stem cell biology make new applications possible for stem cell based technology. Of note, it is now possible to reprogram terminally differentiated human somatic cells into pluripotent cells that are functionally equivalent to embryonic stem cells. These induced pluripotent cells may become the substrate for future disease models and cell-based therapies. In addition, novel techniques for genetic manipulation have increased the ease with which genes can be modified into stem cells. In this review, we describe these novel technologies as well as developments in the understanding of basic biology of stem cell pluripotency and differentiation.

A Practical Guide to Ultrasound-guided Venous Access During Implantation of Pacemakers and Defibrillators.

Ultrasound (US) guidance has been shown to be a safe and effective option for gaining access to the axillary vein during implantation of cardiovascular implantable electronic devices (CIEDs). However, US-based technique has not been universally adopted in CIED implantations performed in cardiac electrophysiology (EP) laboratories, despite potential advantages over other vascular access techniques. For this reason, not all cardiac electrophysiologists have been trained to use US guidance during CIED implantation. This review is intended to provide a practical guide to the use of US guidance to obtain axillary vein access in the EP laboratory setting.

Global disparities in arrhythmia care: Mind the gap.

Delivery of comprehensive arrhythmia care requires the simultaneous presence of many resources. These include complex hospital infrastructure, expensive implantable equipment, and expert personnel. In many low- and middle-income countries (LMICs), at least 1 of these components is often missing, resulting in a gap between the demand for arrhythmia care and the capacity to supply care. In addition to this treatment gap, there exists a training gap, as many clinicians in LMICs have limited access to formal training in cardiac electrophysiology. Given the progressive increase in the burden of cardiovascular diseases in LMICs, these patient care and clinical training gaps will widen unless further actions are taken to build capacity. Several strategies for building arrhythmia care capacity in LMICs have been described. Medical missions can provide donations of both equipment and clinical expertise but are only intermittently present and therefore are not optimized to provide the longitudinal support needed to create self-sustaining infrastructure. Use of donated or reprocessed equipment (eg, cardiac implantable electronic devices) can reduce procedural costs but does not address the need for infrastructure, including diagnostics and expert personnel. Collaborative efforts involving multiple stakeholders (eg, professional organizations, government agencies, hospitals, and educational institutions) have the potential to provide longitudinal support of both patient care and clinician education in LMICs.

Distinct etiologies of high-sensitivity troponin T elevation predict different mortality risks for patients hospitalized with COVID-19.

BACKGROUND: Cardiovascular events in the context of COVID-19 infection increase the risk of negative patient outcomes, but large cohort studies describing this association are limited. The purpose of the current study was to investigate the potential associations between cardiovascular events and mortality in patients hospitalized due to COVID-19. METHODS: A retrospective chart review was performed in 2450 patients hospitalized for confirmed COVID-19 infection within a single hospital network between March 15 and June 15, 2020. Logistic regression analysis was used to identify predictors of mortality. RESULTS: In the study population, 57% of patients had elevated high sensitivity troponin (hs-TnT) levels. Acute heart failure occurred in 23% of patients and arrhythmias were observed in 8% of patients. Of the 1401 patients with elevated hs-TnT levels, a primary cardiac etiology (e.g., myocardial infarction) was identified in 653 (47%) patients. In the remaining 748 (53%) patients, there was evidence of a primary non-cardiac etiology for hs-TnT elevation such as renal failure (n = 304) and critical illness (n = 286). Elevated hs-TnT was associated with increased risk of mortality. A significantly higher mortality rate was observed for hs-TnT elevation associated with a primary cardiac etiology (OR 4.6, 95% CI: 2.7-7.6; P < 0.001) than a primary non-cardiac etiology (OR 2.7, 95% CI: 1.6-4.5; P < 0.001). CONCLUSIONS: Elevated hs-TnT in the context of COVID-19 infection is associated with a significantly increased mortality risk. Hs-TnT elevation in the context of a primary cardiac etiology confers a nearly 2-fold higher mortality risk than hs-TnT elevation due to a primary non-cardiac etiology.

Outcomes of Patients Hospitalized With Cardiovascular Implantable Electronic Device-Related Infective Endocarditis, Prosthetic Valve Endocarditis, and Native Valve Endocarditis: A Nationwide Study, 2003 to 2017.

Background Most published reports describing outcomes of patients with cardiovascular implantable electronic device-related infective endocarditis (CIED-IE) are single-center studies with small patient sample sizes. The goal of this study was to utilize population-based data to assess trends in CIED-IE hospitalization and to compare outcomes between patients hospitalized with CIED-IE, prosthetic valve endocarditis (PVE), and native valve endocarditis (NVE). Methods and Results A query of the National (Nationwide) Inpatient Sample (NIS) database between 2003 and 2017 identified 646 325 patients hospitalized with infective endocarditis in the United States of whom 585 974 (90%) had NVE, 27 257 (4.2%) had CIED-IE, and 26 111 (4%) had PVE. There was a 509% increase in CIED-IE hospitalizations in the United States from 2003 to 2017 (P trend<0.001). In-hospital mortality and length of stay associated with CIED-IE decreased during the study period from 15% and 20 days in 2003 to 9.7% and 19 days in 2017 (P trend=0.032 and 0.018, respectively). The in-hospital mortality rate was lower in patients hospitalized with CIED-IE (9.2%) than in patients with PVE (12%) and NVE (12%). Length of stay was longest in the CIED-IE group (17 compared with 14 days for both NVE and PVE). Hospital costs were highest for the CIED-IE group ($56 000 compared with $37 000 in NVE and $45 000 in PVE). Conclusions Despite the fact that the number of comorbidities per patient with CIED-IE increased during the study period, mortality rate and hospital length of stay decreased. The mortality rate was significantly lower for patients with CIED-IE than for patients with NVE and PVE. Patients with CIED-IE had the longest lengths of stay and highest hospital costs.

Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains.

In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2,000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation, followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes -- the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes, and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells.

Usefulness of electrocardiographic parameters as compared with computed tomography measures of left atrial volume enlargement: from the ROMICAT trial.

INTRODUCTION: The 12-lead surface electrocardiogram (ECG) is commonly used as a noninvasive modality to assess for left atrial enlargement (LAE), but data comparing ECG against cardiac computed tomography (CT) for LAE is lacking. We aimed to determine the diagnostic performance of 6 ECG criteria for LAE as compared with CT left atrial volume (LAV) and index to body surface area (LAVI) as the reference standard. MATERIALS AND METHODS: In 339 patients (age: mean ± mean, 53 ± 12 years; 63% male), we evaluated the quantitative ECG parameters of P duration, P to PR segment ratio, P wave area, and P terminal force in lead V1. We also assessed qualitatively the morphology of bifid and biphasic P waves. Patients were stratified into top and lowest quartile of LAV and LAVI by CT. RESULTS: Of the 6 ECG criteria, patients with P duration greater than 110 milliseconds had a 2½-fold increase likelihood of being in the top quartile of LAV (adjusted odds ratio [OR], 2.51; P = .01) and LAVI (adjusted OR, 2.74; P = .007) as measured by CT. For this ECG criterion, the sensitivity and specificity were 71% and 55% for CT LAE by LAV and 61% and 55% for LAVI. The remaining ECG parameters of LAE assessed (P to PR segment ratio, P terminal force in lead V1, P wave area, bifid, and biphasic P wave) were not associated with LAE by CT-based LAV or LAVI (all P ≥ .20). DISCUSSION: Only P duration greater than 110 milliseconds was independently associated with LAE based on CT-derived LA volume and index. However, none of the established ECG parameters of LAE have sufficient diagnostic accuracies for predicting volumetric enlargement by CT, thus limiting its clinical utility.

MAUDE Database Analysis of Post-Approval Outcomes following Left Atrial Appendage Closure with the Watchman Device.

Left atrial appendage closure (LAAC) is an important strategy to reduce stroke risk in patients with non-valvular atrial fibrillation (AF) who are at high risk of bleeding on long-term anticoagulation. Real-world assessments of the safety of the Watchman LAAC device remain limited. The objective of this study was to determine the frequency and timing of adverse events associated with Watchman LAAC device implants performed after FDA approval. Adverse events associated with Watchman LAAC implants performed between March 2015 and March 2019 were identified through a search of the FDA Manufacturer and User Facility Device Experience (MAUDE) database. During the study period, 3,652 unique adverse events were identified. An estimated 43,802 Watchman implants were performed in the United States during the study period. The overall adverse event rate was 7.3% and the mortality rate was 0.4%. Of the 159 unique types of adverse events identified, pericardial effusion was most common (1.4%). Most adverse events (73%) occurred intraoperatively (59%) or within 1 day of the procedure (15%). However, 19% of deaths, 24% of strokes and 27% of device embolizations occurred >1 month after implantation. The rates of most Watchman-related adverse events reported in the MAUDE database were comparable to those observed in clinical trials. A majority of adverse events occurred within 1 day of implant. In conclusion, while the absolute event rates were low, a significant proportion of device embolizations, strokes, and deaths occurred >1 month after Watchman implant.

A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus.

Chikungunya virus (CHIKV) infection causes acute disease characterized by fever, rash and arthralgia, which progresses to severe and chronic arthritis in up to 50% of patients. Moreover, CHIKV infection can be fatal in infants or immunocompromised individuals and has no approved therapy or prevention. This phase 1, first-in-human, randomized, placebo-controlled, proof-of-concept trial conducted from January 2019 to June 2020 evaluated the safety and pharmacology of mRNA-1944, a lipid nanoparticle-encapsulated messenger RNA encoding the heavy and light chains of a CHIKV-specific monoclonal neutralizing antibody, CHKV-24 ( NCT03829384 ). The primary outcome was to evaluate the safety and tolerability of escalating doses of mRNA-1944 administered via intravenous infusion in healthy participants aged 18-50 years. The secondary objectives included determination of the pharmacokinetics of mRNA encoding for CHKV-24 immunoglobulin heavy and light chains and ionizable amino lipid component and the pharmacodynamics of mRNA-1944 as assessed by serum concentrations of mRNA encoding for CHKV-24 immunoglobulin G (IgG), plasma concentrations of ionizable amino lipid and serum concentrations of CHKV-24 IgG. Here we report the results of a prespecified interim analysis of 38 healthy participants who received intravenous single doses of mRNA-1944 or placebo at 0.1, 0.3 and 0.6 mg kg-1, or two weekly doses at 0.3 mg kg-1. At 12, 24 and 48 h after single infusions, dose-dependent levels of CHKV-24 IgG with neutralizing activity were observed at titers predicted to be therapeutically relevant concentrations (≥1 µg ml-1) across doses that persisted for ≥16 weeks at 0.3 and 0.6 mg kg-1 (mean t1/2 approximately 69 d). A second 0.3 mg kg-1 dose 1 week after the first increased CHKV-24 IgG levels 1.8-fold. Adverse effects were mild to moderate in severity, did not worsen with a second mRNA-1944 dose and none were serious. To our knowledge, mRNA-1944 is the first mRNA-encoded monoclonal antibody showing in vivo expression and detectable ex vivo neutralizing activity in a clinical trial and may offer a treatment option for CHIKV infection. Further evaluation of the potential therapeutic use of mRNA-1944 in clinical trials for the treatment of CHIKV infection is warranted.