Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.

OBJECTIVES: We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit. METHODS: Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data. RESULTS: AP fetuses (n = 13; 102±4d gestational age [term 115d]; 616 ± 139 g [g]; survival 46.4 ± 46.8 h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24 h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24 h. CONCLUSIONS: Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.

Surgical Melody Mitral Valve: A Paradigm Shift for Infants with Unrepairable Mitral Valve Disease.

BACKGROUND: Melody valve (Melody) for mitral valve replacement (MVR)(MelodyMVR) has been an effective strategy to treat unrepairable mitral valve disease in small children. The purpose of this study is to analyze survival, durability, and complications of MelodyMVR strategy. METHODS: Patients who underwent MelodyMVR between 2014 and 2023 were included. Transplant-free survival was analyzed with Kaplan-Meier analysis. Fine and Gray sub-distribution method was applied to quantify the cumulative incidence. RESULTS: Twenty-five patients underwent MelodyMVR. Median age and weight were 6.3 (4.4-15.2) months and 6.36 (4.41-7.57) kg. 60% had congenital mitral valve disease and 52% had dominant mitral regurgitation. The median diameter of the implanted Melody was 16 (14-18) mm. Mortality at 6 months, 1 year, and 5 years was 8.3% (95% CI, 2.2%-29.4%), 12.5% (4.2%-33.9%), and 17.6% (7.0%-40.7%), respectively. Two (8%) hospital survivors required early Melody replacement. Competing risk analysis showed that approximately 50% of patients underwent mechanical MVR by 3.5 years after MelodyMVR. Freedom from bleeding and thrombosis at 4 years was 87.5% (95%CI, 74.2%-100%). Eleven patients underwent mechanical MVR with no mortality. One (9%) required pacemaker implantation after mechanical MVR. CONCLUSIONS: MelodyMVR provides reasonable early and medium-term survival in small children and a high rate of successful bridge to mechanical MVR. MelodyMVR is associated with minimal pacemaker requirement, bleeding, and thrombosis. Early Melody functional deterioration necessitates early re-MVR, which can be achieved with minimal mortality and morbidity.

Longitudinal Evaluation of Congenital Cardiovascular Surgical Performance and Skills Retention Using Silicone-Molded Heart Models.

Objective: Hands-on surgical training (HOST) for congenital heart surgery (CHS), utilizing silicone-molded models created from 3D-printing of patients' imaging data, was shown to improve surgical skills. However, the impact of repetition and frequency of repetition in retaining skills has not been previously investigated. We aimed to longitudinally evaluate the outcome for HOST on two example procedures of different technical difficulties with repeated attempts over a 15-week period. Methods: Five CHS trainees were prospectively recruited. Repair of coarctation of the aorta (CoA) and arterial switch operation (ASO) were selected as example procedures of relatively low and high technical difficulty. Procedural time and technical performance (using procedure-specific assessment tools by the participant, a peer-reviewer, and the proctor) were measured. Results: Coarctation repair performance scores improved after the first repetition but remained unchanged at the follow-up session. Likewise, CoA procedural time showed an early reduction but then remained stable (mean [standard deviation]: 29[14] vs 25[15] vs 23[9] min at 0, 1, and 4 weeks). Conversely, ASO performance scores improved during the first repetitions, but decreased after a longer time delay (>9 weeks). Arterial switch operation procedural time showed modest improvements across simulations but significantly reduced from the first to the last attempt: 119[20] versus 106[28] min at 0 and 15 weeks, P = .049. Conclusions: Complex procedures require multiple HOST repetitions, without excessive time delay to maintain long-term skills improvement. Conversely, a single session may be planned for simple procedures to achieve satisfactory medium-term results. Importantly, a consistent reduction in procedural times was recorded, supporting increased surgical efficiency.

Early outcomes of moderate-to-high-risk pediatric congenital cardiac surgery and predictors of extracorporeal circulatory life support requirement.

Background: Cardiopulmonary failure refractory to medical management after moderate-to-high-risk congenital cardiac surgery may necessitate mechanical support with veno-arterial extracorporeal membrane oxygenation (ECMO). On the extreme, ECMO can also be initiated in the setting of cardiac arrest (extracorporeal cardiopulmonary resuscitation, ECPR) unresponsive to conventional resuscitative measures. Methods: This was a single-center retrospective cohort study of patients (n = 510) aged <3 years old who underwent cardiac surgery with cardiopulmonary bypass with a RACHS-1 score ≥3 between 2011 and 2014. Perioperative factors were reviewed to identify predictors of ECMO initiation and mortality in the operating room (OR) and the intensive care unit (ICU). Results: A total of 510 patients with a mean surgical age of 10.0 ± 13.4 months were included. Among them, 21 (4%) patients received postoperative ECMO-12 were initiated in the OR and 9 in the ICU. ECMO cannulation was associated with cardiopulmonary bypass duration, aortopulmonary shunt, residual severe mitral regurgitation, vaso-inotropic score, and postprocedural lactate (p < 0.001). Of the 32 (6%) total deaths, 7 (22%) were ECMO patients-4 were elective OR cannulations and 3 were ICU ECPR. Prematurity [hazard ratio (HR): 2.61, p < 0.01), Norwood or Damus-Kaye-Stansel procedure (HR: 4.29, p < 0.001), postoperative left ventricular dysfunction (HR: 5.10, p = 0.01), residual severe tricuspid regurgitation (HR: 6.06, p < 0.001), and postoperative ECMO (ECPR: HR: 15.42, p < 0.001 vs. elective: HR: 5.26, p = 0.01) were associated with mortality. The two patients who were electively cannulated in the ICU survived. Discussion: Although uncommon, postoperative ECMO in children after congenital cardiac surgery is associated with high mortality, especially in cases of ECPR. Patients with long cardiopulmonary bypass time, residual cardiac lesions, or increased vaso-inotropic requirement are at higher risk of receiving ECMO. Pre-emptive or early ECMO initiation before deterioration into cardiac arrest may improve survival.

Coronary artery lesions are associated with adverse cardiac events in children undergoing supravalvular aortic stenosis repair.

OBJECTIVES: The aim of this study was to identify the prevalence and anatomic characteristics of coronary artery lesions and their associated postoperative risk in patients undergoing supravalvular aortic stenosis repair. METHODS: The association between structural risk factors, postoperative ST-segment changes, and major adverse cardiac events was explored using logistic regression and the Fisher's exact test. RESULTS: In 51 consecutive patients with supravalvular aortic stenosis treated between 2000 and 2017, a total of 48 coronary lesions were identified in 27 patients (53%). Prominent ostial ridge (type I) was the most common coronary lesion, followed by small ostium with (IIIb) or without (IIIa) diffuse long-segment coronary narrowing, and adhesion of the coronary cusp (type II). There were 54 concomitant coronary procedures, including 43 primary corrections and 11 revisions. Thirty-three patients underwent supravalvular aortic stenosis repair with a bifurcated patch, of which 13 (39.4%) had right coronary artery distortion/kinking requiring patch plication (n = 8) and reimplantation (n = 5). Postoperative major adverse cardiac events (MACE) occurred in 9 patients (17.6%), including 3 deaths, 4 needing mechanical circulatory support, and 6 experiencing ventricular arrhythmias. Twenty-two patients (43.1%) had postoperative ST-segment changes, including 13 early changes that resolved within 24 h and 9 persistent changes lasting >24 h. Patients with type III lesions were associated with postoperative persistent ST-segment change (P = 0.04) and these lesions independently predicted postoperative MACE (P = 0.02). Patients with pre-existing coronary lesions were at elevated risk of right coronary artery distortion/kinking (P = 0.045). CONCLUSIONS: The prevalence of ST-segment changes and MACE is high in patients undergoing supravalvular aortic stenosis repair. The preoperative presence of complex coronary lesions is the most important predictor for postoperative major adverse cardiac events.

Superior cavopulmonary shunt via right vertical axillary mini-thoracotomy.

We present 2 cases of patients with univentricular heart physiology of different anatomic variants who successfully underwent minimally invasive bidirectional cavopulmonary anastomosis via the right vertical axillary mini-thoracotomy.

Minimally Invasive Surgery for Congenital Heart Disease.

Minimally invasive cardiac surgery for congenital heart disease has gained increasing acceptance within the specialty. However, most suitable candidates are still treated with a conventional median sternotomy. Adoption of minimally invasive techniques has proven essential in the surgical repair of acquired heart disease to increase patient satisfaction and to remain competitive in an ever-changing medical field. We herein summarize the currently available literature on minimally invasive congenital heart surgery. We describe available techniques and routes of access as well as the lesions amenable for minimally invasive repairs. Mainly derived from case series and smaller retrospective studies, we report available evidence on outcome, especially compared with conventional repairs through a median sternotomy. We highlight the unique challenges that arise from the wide range of lesions as well as from the spectrum of patients, ranging from infant to adulthood, and describe ways to mitigate those.

Mechanical atrioventricular valve replacement in patients with single ventricle palliation.

OBJECTIVES: Atrioventricular valve (AVV) replacements in patients with single-ventricle circulations pose significant surgical risks and are associated with high morbidity and mortality. METHODS: From 1997 to 2021, 16 consecutive patients with functionally single-ventricle physiology underwent mechanical AVV replacement. Primary outcome was transplant-free survival. Secondary outcomes included major postoperative morbidity. RESULTS: The median age of AVV replacement was 2 years old (interquartile range 0.6-3.8 years). All AVV replacements were performed with a St. Jude Medical mechanical valve, median 24 mm (range, 19-31mm). Extracorporeal membrane oxygenation (ECMO) was required in 4 patients. Operative mortality was 38% (6/16). There were 2 late deaths and 3 transplants. Transplant-free survival was 50% at 1 year, 37.5% at 5 years, and 22% at 10 years. Transplant-free survival was higher for patients with preserved ventricular function (P = 0.01). Difference in transplant-free survival at 1 year was 75% vs 25%, at 5 years was 62.5% vs 12.5% and at 10 years was 57% vs 0%. Three (19%) patients had complete heart block requiring permanent pacemaker insertion. 6 of 13 patients (46%) patients reached Fontan completion (3 patients operated at/after Fontan). Significant bleeding events occurred in 8 patients (50%) with 3 patients suffering major cerebrovascular accidents. There were 6 events of valve thrombosis in 5 patients, resulting in 2 deaths and 2 heart transplants. CONCLUSIONS: Mechanical valve replacement carries significant morbidity and mortality risk. While it successfully salvages about half of patients with preserved ventricular function, careful consideration of alternative options should be made before embarking upon mechanical valve replacement.

Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

OBJECTIVES: During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. DESIGN: Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. SETTING: PICU and cardiac ICU in a quaternary-care center. PATIENTS: Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO ( p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. CONCLUSIONS: There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Advanced imaging of fetal cardiac function.

Over recent decades, a variety of advanced imaging techniques for assessing cardiovascular physiology and cardiac function in adults and children have been applied in the fetus. In many cases, technical development has been required to allow feasibility in the fetus, while an appreciation of the unique physiology of the fetal circulation is required for proper interpretation of the findings. This review will focus on recent advances in fetal echocardiography and cardiovascular magnetic resonance (CMR), providing examples of their application in research and clinical settings. We will also consider future directions for these technologies, including their ongoing technical development and potential clinical value.

Longitudinal Assessment of Cerebral Blood Volume Variation in Human Neonates Using Ultrafast Power Doppler and Diverging Waves.

Longitudinal assessment of brain perfusion is a critical parameter for neurodevelopmental outcome of neonates undergoing cardiopulmonary bypass procedure. In this study, we aim to measure the variations of cerebral blood volume (CBV) in human neonates during cardiac surgery, using Ultrafast Power Doppler and freehand scanning. To be clinically relevant, this method must satisfy three criteria: being able to image a wide field of view in the brain, show significant longitudinal CBV variations, and present reproducible results. To address the first point, we performed for the first time transfontanellar Ultrafast Power Doppler using a hand-held phased-array transducer with diverging waves. This increased the field of view more than threefold compared to previous studies using linear transducers and plane waves. We were able to image vessels in the cortical areas as well as the deep grey matter and temporal lobes. Second, we measured the longitudinal variations of CBV on human neonates undergoing cardiopulmonary bypass. When compared to a pre-operative baseline acquisition, the CBV exhibited significant variation during bypass: on average, + 20±3 % in the mid-sagittal full sector ( [Formula: see text]), - 11±3 % in the cortical regions ( [Formula: see text]) and - 10±4 % in the basal ganglia ( [Formula: see text]). Third, a trained operator performing identical scans was able to reproduce CBV estimates with a variability of 4% to 7.5% depending on the regions considered. We also investigated whether vessel segmentation could further improve reproducibility, but found that it actually introduced greater variability in the results. Overall, this study demonstrates the clinical translation of ultrafast power Doppler with diverging-waves and freehand scanning.

Impact of cardiopulmonary bypass on cerebrovascular autoregulation assessed by ultrafast ultrasound imaging.

Newborns with congenital heart disease undergoing cardiac surgery are at risk of neurodevelopmental impairment with limited understanding of the impact of intra-operative cardiopulmonary bypass (CPB), deep hypothermia and selective cerebral perfusion on the brain. We hypothesized that a novel ultrasound technique, ultrafast power Doppler (UPD), can assess variations of cerebral blood volume (CBV) in neonates undergoing cardiac surgery requiring CPB. UPD was performed before, during and after surgery in newborns with hypoplastic left heart syndrome undergoing a Norwood operation. We found that global CBV was not significantly different between patients and controls (P = 0.98) and between pre- and post-surgery (P = 0.62). UPD was able to monitor changes in CBV throughout surgery, revealing regional differences in CBV during hypothermia during which CBV correlated with CPB flow rate (R2  = 0.52, P = 0.021). Brain injury on post-operative magnetic resonance imaging was observed in patients with higher maximum variation in CBV. Our findings suggest that UPD can quantify global and regional brain perfusion variation during neonatal cardiac surgery with this first intra-operative application demonstrating an association between CBV and CPB flow rate, suggesting loss of autoregulation. Therefore, the measurement of CBV by UPD could enable optimization of cerebral perfusion during cardiac surgery in neonates. KEY POINTS: The impact of cardiopulmonary bypass (CPB) on the neonatal brain undergoing cardiac surgery is poorly understood. Ultrafast power Doppler (UPD) quantifies cerebral blood volume (CBV), a surrogate of brain perfusion. CBV varies throughout CPB surgery and is associated with variation of the bypass pump flow rate during deep hypothermia. Association between CBV and bypass pump flow rate suggests loss of cerebrovascular autoregulatory processes. Quantitative monitoring of cerebral perfusion by UPD could provide a direct parameter to optimize CPB flow rate.

Cardioprotective Actions of a Glucagon-like Peptide-1 Receptor Agonist on Hearts Donated After Circulatory Death.

Background Heart transplantation with a donation after circulatory death (DCD) heart is complicated by substantial organ ischemia and ischemia-reperfusion injury. Exenatide, a glucagon-like peptide-1 receptor agonist, manifests protection against cardiac ischemia-reperfusion injury in other settings. Here we evaluate the effects of exenatide on DCD hearts in juvenile pigs. Methods and Results DCD hearts with 15-minutes of global warm ischemia after circulatory arrest were reperfused ex vivo and switched to working mode. Treatment with concentration 5-nmol exenatide was given during reperfusion. DCD hearts treated with exenatide showed higher myocardial oxygen consumption (exenatide [n=7] versus controls [n=7], over 60-120 minutes of reperfusion, P<0.001) and lower cardiac troponin-I release (27.94±11.17 versus 42.25±11.80 mmol/L, P=0.04) during reperfusion compared with controls. In working mode, exenatide-treated hearts showed better diastolic function (dp/dt min: -3644±620 versus -2193±610 mm Hg/s, P<0.001; Tau: 15.62±1.78 versus 24.59±7.35 milliseconds, P=0.02; lateral e' velocity: 11.27 ± 1.46 versus 7.19±2.96, P=0.01), as well as lower venous lactate levels (3.17±0.75 versus 5.17±1.44 mmol/L, P=0.01) compared with controls. Higher levels of activated endothelial nitric oxide synthase (phosphorylated to total endothelial nitric oxide synthase levels: 2.71±1.16 versus 1.37±0.35, P=0.02) with less histological evidence of endothelial damage (von Willebrand factor expression: 0.024±0.007 versus 0.331±0.302, pixel/µm, P=0.04) was also observed with exenatide treatment versus controls. Conclusions Acute treatment of DCD hearts with exenatide limits myocardial and endothelial injury and improves donor cardiac function.

Modified Warden Procedure for Partial Anomalous Pulmonary Venous Drainage to Promote Growth.

Extreme forms of partially anomalous pulmonary venous drainage with high entrance of the pulmonary veins into the superior caval vein can be challenging to correct without obstructing both systemic and pulmonary venous pathways. We report an unusual morphologic subform of this malformation and a surgical technique to address its specific anatomic peculiarities while maintaining growth potential of the venous pathways. We highlight that even such complex reconstructions can be performed minimally invasively.

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit (n = 12; 98 ± 4 days; 743 ± 350 g). The umbilical vessels were cannulated, and fetuses were supported for 46.4 ± 46.8 h using the pumped AP versus 11 ± 13 h on the pumpless AP circuit. Upon initiation of AP support on the pumped system, we observed supraphysiologic circuit flows, tachycardia, and hypertension, while animals maintained on a pumpless AP circuit exhibited subphysiologic flows. On the pumped AP circuit, there was a progressive decline in umbilical vein (UV) flow and oxygen delivery. We conclude that the addition of a centrifugal pump to the AP circuit improves survival of preterm pigs by augmenting UV flow through the reduction of right ventricular afterload. However, we continued to observe the development of heart failure within a matter of days.

Surgical Strategies in Single Ventricle Management of Neonates and Infants.

No area of congenital heart disease has undergone greater change and innovation than single ventricle management over the past 20 years. Surgical and catheterisation laboratory interventions have transformed outcomes such that in some subgroups more than 80% of the patients can survive into adulthood. Driven by parallel development in diagnostic imaging and cardiac intensive care, surgical management is focused on the neonatal period as the key time to creating a balanced circulation and limiting pulmonary blood flow. Different configurations of the circulation, including new types of surgical shunts, and the role of "hybrid" circulations provide greater options and better physiology. This overview focuses on these changes in surgical management and timing, but also looks at the exciting areas of regenerative therapies to improve ventricular function, and the concept of ventricular rehabilitation to achieve biventricular circulations in certain groups of patients. The importance of early (neonatal) intervention and multidisciplinary approach to management is emphasised, as well as looking beyond simply survival to also improving neurodevelopmental outcomes.

Branch pulmonary artery stenosis after arterial switch operation: The effect of preoperative anatomic factors on reintervention.

BACKGROUND: We hypothesized that preoperative patient characteristics and branch pulmonary artery (PA) size might influence the rate of postoperative branch PA reintervention in patients with transposition of the great arteries who undergo the arterial switch operation (ASO). METHODS: The retrospective single-center study included 262 consecutive (2008-2017) newborns who underwent the ASO. Demographic characteristics, echocardiography, and clinical outcomes were reviewed. Competing risk analysis modeled incidence of branch PA reintervention and cause-specific hazard regression for predictors analyses. RESULTS: Median age and weight were 7 (range, 5-11) days and 3.4 (range, 3.1-3.8) kg, respectively. Various types of early branch PA reinterventions (concomitant revision or reintervention during the intensive care unit stay) were required in 28 (10.7%) patients. These patients had prolonged ventilation (P < .001), intensive care unit duration (P < .001), worse right ventricular function (P = .043), and high in-hospital mortality (P = .010). Branch PA dimensions significantly decreased immediately after ASO compared with baseline measurements. The median follow-up duration was 20.8 (range, 0.9-44.7) months. Branch PA reintervention was common among survivors without early reinterventions (9.4%), and even more frequent among those with early reinterventions (25%). Subsequent reintervention (all catheter-based) was necessary for more than one-third of patients after initial branch PA reintervention. The multivariable analysis showed preoperative dimension of the left PA (hazard ratio, 0.527 [95% CI, 0.337-0.823]; P = .005), and right PA (hazard ratio, 0.503 [95% CI, 0.318-0.796]; P = .003) were independently associated with late branch PA reinterventions. CONCLUSIONS: Branch PA reintervention was common and often required surgical or catheter-based reinterventions after ASO. PA branch diameters became significantly smaller after ASO. Smaller preoperative branch PA predicted late branch PA reintervention, indicating a smaller margin of geometrical tolerance to this effect.

Anti-SARS-CoV-2 mRNA vaccines as inducers of humoral response against apolipoprotein A-1?

BACKGROUND: COVID-19 and some anti-SARS-CoV-2 vaccines trigger a humoral autoimmune response against a broad range of endogenous components, which may affect recipients' prognosis in predisposed individuals. Autoantibodies directed against apolipoprotein A-1 (AAA1 IgG) the major protein fraction of High Density Lipoprotein have been shown to be raised in COVID-19 and in rheumatoid arthritis (RA) patients and other populations where they have been associated with poorer outcomes. We wanted to assess the impact of anti-SARS-CoV-2 mRNA-based vaccination on AAA1 autoimmune biomarkers in RA patients. METHODS: 20 healthy controls and 77 RA mRNA-based vaccinated patients were collected at baseline, 3 weeks after the first vaccination, 2 and 8 weeks after the second vaccination. AAA1 and SARS-CoV-2 serologies were measured by immunoassays. Systemic and local symptoms occurring during the vaccination protocol were recorded. RESULTS: mRNA-based vaccination induced a significant increase in median AAA1 IgG levels in both healthy controls and RA patients overtime. However, in both populations, these medians trend did not translate into significant increase in AAA1 IgG seropositivity rates despite evolving from 5 to 10% in healthy controls, and from 9 to 12.9% in RA patients. No associations were retrieved between AAA1 IgG and symptoms of any kind during the vaccination protocol. CONCLUSIONS: mRNA-based vaccination seems to induce a light AAA1 IgG response in immunocompetent individuals within 2 months after the last injection. Although we did not observe any warning signs, the formal demonstration of the harmlessness of such biological warrants further studies.