Role of Circulating Angiotensin Converting Enzyme 2 in Left Ventricular Remodeling following Myocardial Infarction: A Prospective Controlled Study.

Angiotensin-converting enzyme 2 (ACE2) cleaves Angiotensin-II to Angiotensin-(1-7), a cardioprotective peptide. Serum soluble ACE2 (sACE2) activity is raised in chronic heart failure, suggesting a compensatory role in left ventricular dysfunction. Our aim was to study the relationship between sACE2 activity, infarct size, left ventricular systolic function and remodeling following ST-elevation myocardial infarction (STEMI). A contrast-enhanced cardiac magnetic resonance study was performed acutely in 95 patients with first STEMI and repeated at 6 months to measure LV end-diastolic volume index, ejection fraction and infarct size. Baseline sACE2 activities, measured by fluorescent enzymatic assay 24 to 48 hours and at 7 days from admission, were compared to that obtained in 22 matched controls. Patients showed higher sACE2 at baseline than controls (104.4 [87.4-134.8] vs 74.9 [62.8-87.5] RFU/µl/hr, p<0.001). At seven days, sACE2 activity significantly increased from baseline (115.5 [92.9-168.6] RFU/µl/hr, p<0.01). An inverse correlation between sACE2 activity with acute and follow-up ejection fraction was observed (r = −0.519, p<0.001; r = −0.453, p = 0.001, respectively). Additionally, sACE2 directly correlated with infarct size (r = 0.373, p<0.001). Both, infarct size (β = −0.470 [95%CI:−0.691:−0.248], p<0.001) and sACE2 at 7 days (β = −0.025 [95%CI:−0.048:−0.002], p = 0.030) were independent predictors of follow-up ejection fraction. Patients with sACE2 in the upper tertile had a 4.4 fold increase in the incidence of adverse left ventricular remodeling (95% confidence interval: 1.3 to 15.2, p = 0.027). In conclusion, serum sACE2 activity rises in relation to infarct size, left ventricular systolic dysfunction and is associated with the occurrence of left ventricular remodeling

Association of central obesity with unique cardiac remodelling in young adults born small for gestational age

Being born small for gestational age (SGA, 10% of all births) is associated with increased risk of cardiovascular mortality in adulthood together with lower exercise tolerance, but mechanistic pathways are unclear. Central obesity is known to worsen cardiovascular outcomes, but it is uncertain how it affects the heart in adults born SGA. We aimed to assess whether central obesity makes young adults born SGA more susceptible to cardiac remodelling and dysfunction.A perinatal cohort from a tertiary university hospital in Spain of young adults (30-40 years) randomly selected, 80 born SGA (birth weight below 10th centile) and 75 with normal birth weight (controls) was recruited. We studied the associations between SGA and central obesity (measured via the hip-to-waist ratio and used as a continuous variable) and cardiac regional structure and function, assessed by cardiac magnetic resonance using statistical shape analysis. Both SGA and waist-to-hip were highly associated to cardiac shape (F = 3.94, P < 0.001; F = 5.18, P < 0.001 respectively) with a statistically significant interaction (F = 2.29, P = 0.02). While controls tend to increase left ventricular end-diastolic volumes, mass and stroke volume with increasing waist-to-hip ratio, young adults born SGA showed a unique response with inability to increase cardiac dimensions or mass resulting in reduced stroke volume and exercise capacity.SGA young adults show a unique cardiac adaptation to central obesity. These results support considering SGA as a risk factor that may benefit from preventive strategies to reduce cardiometabolic risk.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: [email protected]

Impact of left atrial volume, sphericity, and fibrosis on the outcome of catheter ablation for atrial fibrillation

INTRODUCTION: To investigate the relation between left atrial (LA) volume, sphericity, and fibrotic content derived from contrast-enhanced cardiac magnetic resonance imaging (CE-CMR) and their impact on the outcome of catheter ablation for atrial fibrillation (AF). METHODS AND RESULTS: In 83 patients undergoing catheter ablation for AF, CE-CMR was used to assess LA volume, sphericity, and fibrosis. There was a significant correlation between LA volume and sphericity (R = 0.535, P < 0.001) and between LA volume and fibrosis (R = 0.241, P = 0.029). Multivariate analyses demonstrated that LA volume was the strongest independent predictor of AF recurrence after catheter ablation (1.019, P = 0.018). CONCLUSION: LA volume, sphericity, and fibrosis were closely related; however, LA volume was the strongest predictor of AF recurrence after catheter ablation

Combined Area of Left and Right Atria May Outperform Atrial Volumes as a Predictor of Recurrences after Ablation in Patients with Persistent Atrial Fibrillation—A Pilot Study

Background and Objectives: Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. Materials and Methods: This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.1%] persistent AF). Four-chamber cine-sequence was selected to measure LA and RA area, and ventricular end-systolic image phase to obtain atrial 3D volumes. The effect of different variables on event-free survival was investigated using the Cox proportional hazards model. Results: In patients with persistent AF, combined LA and RA area indexed to body surface area (AILA + RA) predicted AF recurrences (HR = 1.08, 95% CI 1.00-1.17, p = 0.048). An AILA + RA cut-off value of 26.7 cm2/m2 had 72% sensitivity and 73% specificity for predicting recurrences in patients with persistent AF. In this group, 65% of patients with AILA + RA > 26.7 cm2/m2 experienced AF recurrence within 2 years of follow-up (median follow-up 11 months), compared to 25% of patients with AILA + RA ≤ 26.7 cm2/m2 (HR 4.28, 95% CI 1.50-12.22; p = 0.007). Indices of LA and RA dilatation did not predict AF recurrences in patients with paroxysmal AF. Atrial 3D volumes did not predict AF recurrences after ablation. Conclusions: In this pilot study, the simple measurement of AILA + RA may predict recurrences after ablation of persistent AF, and may outperform measurements of atrial volumes. In paroxysmal AF, atrial dilatation did not predict recurrences. Further studies on the role of RA and LA remodelling are needed

Recurrent NOMO1 gene deletion is a potential clinical marker in early-onset colorectal cancer and is involved in the regulation of cell migration

The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 (NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1, there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC–IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial–mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.This study was supported by the health research program of the Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness, PI20/01569 and PI20/0974), co-funded by FEDER funds, and Mutua Madrileña Foundation (FMM20/001). A.M.-M was supported by a predoctoral research grant from the Dr. Moraza Fundation (FMoraza18/001). P.G.V and N.G.-U were supported by a predoctoral research grant from the Consejería de Educación—Junta de Castilla y León. A.N.H. was supported by the National Institutes of Health K12 HD043483 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Scar channels in cardiac magnetic resonance to predict appropriate therapies in primary prevention.

Background Scar characteristics analyzed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related with ventricular arrhythmias. Current guidelines are based only on the left ventricular ejection fraction to recommend an implantable cardioverter-defibrillator (ICD) in primary prevention. Objectives Our study aims to analyze the role of imaging to stratify arrhythmogenic risk in patients with ICD for primary prevention. Methods From 2006 to 2017, we included 200 patients with LGE-CMR before ICD implantation for primary prevention. The scar, border zone, core, and conducting channels (CCs) were automatically measured by a dedicated software. Results The mean age was 60.9 ± 10.9 years; 81.5% (163) were men; 52% (104) had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 29% ± 10.1%. After a follow-up of 4.6 ± 2 years, 46 patients (22%) reached the primary end point (appropriate ICD therapy). Scar mass (36.2 ± 19 g vs 21.7 ± 10 g; P 10 g (25.31% vs 5.26%; hazard ratio 4.74; P = .034) and the presence of CCs (34.75% vs 8.93%; hazard ratio 4.07; P = .003) were also strongly associated with the primary end point. However, patients without channels and with scar mass < 10 g had a very low rate of appropriate therapies (2.8%). Conclusion Scar characteristics analyzed by LGE-CMR are strong predictors of appropriate therapies in patients with ICD in primary prevention. The absence of channels and scar mass < 10 g can identify patients at a very low risk of ventricular arrhythmias in this population

Progressive and Simultaneous Right and Left Atrial Remodeling Uncovered by a Comprehensive Magnetic Resonance Assessment in Atrial Fibrillation

Background Left atrial structural remodeling contributes to the arrhythmogenic substrate of atrial fibrillation (AF), but the role of the right atrium (RA) remains unknown. Our aims were to comprehensively characterize right atrial structural remodeling in AF and identify right atrial parameters predicting recurrences after ablation. Methods and Results A 3.0 T late gadolinium enhanced-cardiac magnetic resonance was obtained in 109 individuals (9 healthy volunteers, 100 patients with AF undergoing ablation). Right and left atrial volume, surface, and sphericity were quantified. Right atrial global and regional fibrosis burden was assessed with validated thresholds. Patients with AF were systematically followed after ablation for recurrences. Progressive right atrial dilation and an increase in sphericity were observed from healthy volunteers to patients with paroxysmal and persistent AF; fibrosis was similar among the groups. The correlation between parameters recapitulating right atrial remodeling was mild. Subsequently, remodeling in both atria was compared. The RA was larger than the left atrium (LA) in all groups. Fibrosis burden was higher in the LA than in the RA of patients with AF, whereas sphericity was higher in the LA of patients with persistent AF only. Fibrosis, volume, and surface of the RA and LA, but not sphericity, were strongly correlated. Tricuspid regurgitation predicted right atrial volume and shape, whereas diabetes was associated with right atrial fibrosis burden; sex and persistent AF also predicted right atrial volume. Fibrosis in the RA was mostly located in the inferior vena cava-RA junction. Only right atrial sphericity is significantly associated with AF recurrences after ablation (hazard ratio, 1.12 [95% CI, 1.01-1.25]). Conclusions AF progression associates with right atrial remodeling in parallel with the LA. Right atrial sphericity yields prognostic significance after ablation

Utilidad de la resonancia magnética en pacientes con fibrilación auricular tributarios de tratamiento con ablación percutánea de las venas pulmonares

[spa] a) Antecedentes.La ablación percutánea mediante radiofrecuencia (APRF) de las venas pulmonares (VPs) es un tratamiento efectivo en pacientes con fibrilación auricular (FA). Sin embargo, su impacto en los volúmenes y función auricular izquierdas no han sido plenamente estudiados. La estenosis de las VPs es una complicación potencial del procedimiento ablativo, pero su incidencia es incierta.b) Hipótesis.- La RM es una técnica que podría ser de utilidad en el estudio anatómico de las VPs y de la AI y en la cuantificación de los volúmenes auriculares y de la función contráctil auricular izquierda antes y después de la ablación percutánea de la FA mediante radiofrecuencia.- Los cambios volumétricos auriculares medidos por RM podrían ser un predictor de respuesta al tratamiento a medio plazo.- La RM permitiría la detección de estenosis de las VPs en pacientes sometidos a APRF.c) Objetivos.- Valorar y demostrar la utilidad de la RM en pacientes con FA tributarios de APRF de las VPs.- Evaluar los cambios volumétricos y funcionales de la AI tras la APRF.- Evaluar la incidencia de estenosis en relación al procedimiento ablativo.d) Metodología.Los cambios volumétricos auriculares se evaluaron en una serie de 55 pacientes sometidos a ablación circunferencial de las VPs (ACVP) a los que se practicó RM antes y 4-6 meses después del procedimiento. Se evaluó el volumen telediastólico auricular izquierdo (Vmax), el volumen telesistólico (Vmin) así como la fracción de eyección auricular izquierda (FEAI).La incidencia de estenosis de las VPs se evaluó mediante RM en una serie de 73 pacientes con FA refractaria al tratamiento médico sometidos a APRF de las VPs, bien mediante técnica de ablación segmentaria ostial selectiva (ASOS) o bien mediante ACVP.e) ResultadosDe los 55 pacientes con RM de seguimiento, 38 (69.1%) se mantuvieron libres de arritmia (grupo I), mientras que los 17 pacientes restantes tuvieron recurrencia de la arritmia (grupo II) durante un periodo de seguimiento de 11.8 ± 7.2 meses. El Vmax medio tras la ACVP disminuyó tanto en el grupo I como en el grupo II. Sin embargo, el Vmin medio sólo disminuyó significativamente en el grupo I. Consecuentemente, no hubo cambios significativos en la FE AI media tras la ablación en el grupo I . (40±11% vs 38±10%; p=0.27). De hecho, la FE AI permaneció estable o aumentó en el 68% de pacientes sin recurrencia de la arritmia tras la ACVP, mientras que en el grupo II se observó una disminución de la FE AI media (37±10% vs 27±10%; p<0.001). La única variable independiente asociada con recurrencia de la arritmia en el modelo multivariado fue el Vmin medido tras el procedimiento ablativo, con riesgo relativo de 1.04 (intervalo de confianza del 95%, 1.02-1.06, p < 0.001).En el segundo estudio la ablación se realizó mediante el procedimiento de ASOS en 32 pacientes y en 41 la ablación se realizó mediante el método de ACVP. No hubo diferencias significativas en la tasa de eficacia del procedimiento según la técnica empleada durante un período de seguimiento de 14.7 ± 12.2 meses. Sin embargo, la incidencia de estenosis de VPs fue mayor en el grupo tratado con ASOS (18.8% vs 0%, p=0.005).f) Conclusiones- Los resultados de esta tesis demuestran que la RM, como técnica de imagen no invasiva, es útil en el estudio anatómico sistemático de las VPs y de la AI en pacientes con FA tributarios de APRF.- La capacidad contráctil de la AI se conserva o incluso mejora en la mayoría de pacientes con buena respuesta a la ACVP. El Vmin de la AI sólo disminuye en los pacientes sin recurrencia de la FA, siendo el Vmin de la AI post-ablación un predictor de respuesta al tratamiento.- La incidencia de estenosis depende de la técnica ablativa utilizada, pudiendo aparecer en los pacientes tratados con ASOS, mientras que es una complicación muy infrecuente en los pacientes tratados mediante ACVP.[eng] "USEFULNESS OF MAGNETIC RESONANCE IMAGING IN PATIENTS HAVING PERCUTANEOUS PULMONARY VEIN ABLATION OF ATRIAL FIBRILLATION"TEXT:Pulmonary vein (PV) radiofrequency ablation is a curative procedure for patients with atrial fibrillation(AF). However, his relationship with left atrial (LA) contractility is limited. PV stenosis has been recognized as a potential complication of the ablation procedure, but its incidence remains unclear.Magnetic Resonance Imaging (MRI) may be an accurate and reproducible technique for depicting the anatomical structures of LA and PVs and to quantify LA volumes and LA ejection fraction (LA EF).Changes in LA volumes may be a predictor of the outcome of the procedure. PV stenosis after AF ablation may be a complication related to the ablation technique.Changes in LA volumes were evaluated in a series of 55 consecutive patients who underwent (MRI) before and 4-6 months after circumferential PV ablation (CPVA). LA end-diastolic (LAmax) and LA end-systolic (LAmin) volumes were measured. During a mean follow-up of 12 ± 7 months, 38 patients (69%) were arrhythmia free. There was a significant decrease in mean LAmax volume in both groups, whereas mean LAmin volume only decreased in patients without recurrences. Mean LA EF was preserved after CPVA in patients arrthythmiafree (40 ± 11% vs 38 ± 10%; P = 0.27) but decreased in patients with AF relapses (37 ± 10% vs 27 ± 10%; P < 0.001).The incidence of PV stenosis was analysed in a series of 73 consecutive patients. Selective segmental ostial ablation (SSOA) was performed in 32 patients, and the remaining 41 patients underwent CPVA. Six patients had a significant PV stenosis, all in SSOA group none in CPVA group (18.8% vs 0%; p= 0.005). The results of these studies confirm that MRI is useful for the anatomic study of PVs and LA. The technique is accurate for:1. Quantifying LA volumes and LA EF2. Identifying anatomical variants of the LA and PV stenosisLAmax volume reduction after CPVA occurs regardless of the clinical efficacy of the procedure, whereas LAmin volume decreases only in patients free of arrhythmia recurrences. LA EF is preserved or even increased in the majority of patients after successful PV ablation.PV stenosis is a potential complication of the SSOA of AF. The PV stenosis is seldom observed in CPVA approach