Cardiac safety of ribociclib evaluated with 24-hour rhythm Holter electrocardiogram.

OBJECTIVE: We aimed to evaluate cardiac safety profile of ribociclib with 24-h rhythm Holter ECG. MATERIAL AND METHOD: Forty-two female metastatic breast cancer patients were included in the study. Rhythm Holter ECG was performed before starting treatment with ribociclib and after 3 months of the treatment initiation. RESULTS: The mean age of the patients was 56.36 ± 12.73. 52.4% (n = 22) of the patients were using ribociclib in combination with fulvestrant and 47.6% (n = 20) with aromatase inhibitors. None of the patients developed cardiotoxicity. When the rhythm Holter results before and in third month of the treatment were compared, there was no statistically significant difference. CONCLUSION: This is the first study evaluating effects of ribociclib treatment on cardiac rhythm with Holter ECG. The findings suggested ribociclib has a low risk of causing early cardiotoxicity.

Reference ranges for ambulatory heart rate measurements in a middle-aged population.

BACKGROUND: Elevated heart rate (HR) predicts cardiovascular disease and mortality, but there are no established normal limits for ambulatory HR. We used data from the Swedish CArdioPulmonary Imaging Study to determine reference ranges for ambulatory HR in a middle-aged population. We also studied clinical correlates of ambulatory HR. METHODS: A 24-hour ECG was registered in 5809 atrial fibrillation-free individuals, aged 50-65 years. A healthy subset (n=3942) was used to establish reference values (excluding persons with beta-blockers, cardiovascular disease, hypertension, heart failure, anaemia, diabetes, sleep apnoea or chronic obstructive pulmonary disease).Minimum HR was defined as the lowest 1-minute HR. Reference ranges are reported as means±SDs and 2.5th-97.5th percentiles. Clinical correlates of ambulatory HR were analysed with multivariable linear regression. RESULTS: The average mean and minimum HRs were 73±9 and 48±7 beats per minute (bpm) in men and 76±8 and 51±7 bpm in women; the reference range for mean ambulatory HR was 57-90 bpm in men and 61-92 bpm in women. Average daytime and night-time HRs are also reported. Clinical correlates, including age, sex, height, body mass index, physical activity, smoking, alcohol intake, diabetes, hypertension, haemoglobin level, use of beta-blockers, estimated glomerular filtration rate, per cent of predicted forced expiratory volume in 1 s and coronary artery calcium score, explained <15% of the interindividual differences in HR. CONCLUSION: Ambulatory HR varies widely in healthy middle-aged individuals, a finding with relevance for the management of patients with a perception of tachycardia. Differences in ambulatory HR between individuals are largely independent of common clinical correlates.

Defining the blanking period, using continuous ECG monitoring, after cryoballoon pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. A blanking period (BP) of 3 months is used in clinical trials and practice. However, the optimal BP duration after PVI remains undefined. OBJECTIVE: The aim of this study was to objectively define, using continuous monitoring by an implantable loop recorder, the optimal BP duration after cryoballoon PVI. METHODS: We enrolled consecutive patients who had cryoballoon PVI and an implantable loop recorder. We determined the time of the last confirmed episode of AF within the blanking period. This was then correlated with AF recurrence in the first year after ablation. RESULTS: There were 210 patients (66 ± 9 years; 138 [66%] male; 116 [55%] paroxysmal AF; CHA2DS2-VASc score, 2.5 ± 1.6). We defined 4 distinct groups based on the last AF episode within the BP: no AF days 0-90 (n = 96 [46%]) and last AF 0-30 days (n = 46 [22%]), 31-60 days (n = 18 [9%]), and 61-90 days (n = 50 [24%]). After the 3-month BP, 101 (48%) patients had AF recurrence at 160 ± 86 days. Compared with patients with no AF in the BP, those with recurrent AF and AF burden >0% 30 days after ablation had a significantly greater AF recurrence during long-term follow-up (P = .001). CONCLUSION: Our data show that the approximately one-third of patients in whom AF occurs and who have a burden of >0% after the first month that follows PVI are at significantly higher risk of long-term recurrent AF. We therefore suggest that the blanking period be limited to a month after cryoballoon PVI.

Breast MRI in patients with implantable loop recorder: initial experience.

OBJECTIVES: To investigate the feasibility of breast MRI exams and guided biopsies in patients with an implantable loop recorder (ILR) as well as the impact ILRs may have on image interpretation. MATERIALS AND METHODS: This retrospective study examined breast MRIs of patients with ILR, from April 2008 to September 2022. Radiological reports and electronic medical records were reviewed for demographic characteristics, safety concerns, and imaging findings. MR images were analyzed and compared statistically for artifact quantification on the various pulse sequences. RESULTS: Overall, 40/82,778 (0.049%) MRIs during the study period included ILR. All MRIs were completed without early termination. No patient-related or device-related adverse events occurred. ILRs were most commonly located in the left lower-inner quadrant (64.6%). The main artifact was a signal intensity (SI) void in a dipole formation in the ILR bed with or without areas of peripheral high SI. Artifacts appeared greatest in the cranio-caudal axis (p < 0.001), followed by the anterior-posterior axis (p < 0.001), and then the right-left axis. High peripheral rim-like SI artifacts appeared on the post-contrast and subtracted T1-weighted images, mimicking suspicious enhancement. Artifacts were most prominent on diffusion-weighted (p < 0.001), followed by T2-weighted and T1-weighted images. In eight patients, suspicious findings were found on MRI, resulting in four additional malignant lesions. Of six patients with left breast cancer, the tumor was completely visible in five cases and partially obscured in one. CONCLUSION: Breast MRI is feasible and safe among patients with ILR and may provide a significant diagnostic value, albeit with localized, characteristic artifacts. CLINICAL RELEVANCE STATEMENT: Indicated breast MRI exams and guided biopsies can be safely performed in patients with implantable loop recorder. Nevertheless, radiologists should be aware of associated limitations including limited assessment of the inner left breast and pseudo-enhancement artifacts. KEY POINTS: • Breast MRI in patients with an implantable loop recorder is an infrequent, feasible, and safe procedure. • Despite limited breast visualization of the implantable loop recorder bed and characteristic artifacts, MRI depicted additional lesions in 8/40 (20%) of cases, half of which were malignant. • Breast MRI in patients with an implantable loop recorder should be performed when indicated, taking into consideration typical associated artifacts.

Neuroimmune modulation mediated by IL-6: A potential target for the treatment of ischemia-induced ventricular arrhythmias.

BACKGROUND: Neural remodeling in the left stellate ganglion (LSG), as mediated by neuroimmune reactions, promotes cardiac sympathetic nerve activity (SNA) and thus increases the incidence of ventricular arrhythmias (VAs). Interleukin-6 (IL-6) is an important factor of the neuroimmune interaction. OBJECTIVE: The present study explored the effects of IL-6 on LSG hyperactivity and the incidence of VAs. METHODS: Eighteen beagles were randomly allocated to a control group (saline with myocardial infarction [MI], n = 6), adeno-associated virus (AAV) group (AAV with MI, n = 6), and IL-6 group (overexpression of IL-6 via AAV vector with MI, n = 6). Ambulatory electrocardiography was performed before and 30 days after AAV microinjection into the LSG. LSG function and ventricular electrophysiology were assessed at 31 days after surgery, and a canine MI model was established. Samples of the LSG were collected for immunofluorescence staining and molecular biological evaluation. Blood samples and 24-hour Holter data were obtained from 24 patients with acute MI on the day after they underwent percutaneous coronary intervention to assess the correlation between IL-6 levels and SNA. RESULTS: IL-6 overexpression increased cardiac SNA and worsened postinfarction VAs. Furthermore, sustained IL-6 overexpression enhanced LSG function, promoted expression of nerve growth factor, c-fos, and fos B in the LSG, and activated the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway. Clinical sample analysis revealed a correlation between serum IL-6 levels and heart rate variability frequency domain index as well as T-wave alternans. CONCLUSION: IL-6 levels are correlated with cardiac SNA. Chronic overexpression of IL-6 mediates LSG neural remodeling through the signal transducer and activator of transcription 3/regulator of G protein signalling 4 signaling pathway, elevating the risk of VA after MI.

Multimodality imaging in patients with implantable loop recorders: Tips and tricks.

An implantable loop recorder (ILR) is a leadless rectangular device used for prolonged electrocardiographic monitoring for up to 3 years. This miniaturized device, inserted subcutaneously, allows clinicians to investigate possible cardiac rhythm disturbances in patients suffering from recurrent unexplained syncope. As the age of the population increases rapidly and the number of ILR patients amplifies, the clinical significance of ILRs is undeniable. Although radioopaque and easily seen on plain chest radiographs and other imaging modalities, ILRs may represent a challenge for clinicians and radiologists to recognize their classic appearance and differentiate them from numerous other cardiac devices. This article aims to summarize current literature on ILRs, their basic function, types, and indications for implantation, but most of all, it aims to familiarize clinicians and radiologists with common imaging features of these devices, safety issues, and artifact-reducing methods. Specifically, this review discusses the typical appearance of ILRs on major diagnostic imaging modalities, including chest X-ray, mammography, ultrasonography, computed tomography, and magnetic resonance imaging (MRI). Furthermore, optimization strategies to mitigate image artifacts and safety issues regarding MRI are discussed.

Cuantificación de la extrasistolía supraventricular y ventricular en el holter de 24 horas: significación pronóstica en estudios actuales / Quantification and clinical significance of supraventricular and ventricular extrasystoles in holter recordings: a review

En la actualidad existen diferencias en la interpretación y cuantificación de los extrasístoles supraventriculares y ventriculares en el Holter de ritmo cardíaco y no existe siempre una misma definición e interpretación de lo que se denomina como "escaso", "ocasional", "frecuente" o "muy frecuente". El objetivo del presente trabajo ha sido revisar las evidencias actuales y sus fundamentos en relación a la cuantificación o carga de la extrasistolía supraventricular y ventricular en un Holter de ritmo cardíaco, lo que debiera contribuir a una mayor precisión y mejor interpretación de la información cuantitativa en la práctica clínica diaria con este examen. Se revisa en la literatura el concepto de carga de extrasístoles supraventriculares y ventriculares y su relación con eventos clínicos: fibrilación auricular y accidente cerebrovascular en el caso de la extrasistolía supraventricular y mortalidad post infarto y deterioro de la función ventricular en el caso de la extrasistolía ventricular. De esta manera se cuantifica en base a la evidencia la extrasistolía supraventricular y ventricular.

Considerable differences exist in the quantification and clinical significance of both supraventricular and ventricular extrasystoles found in Holter recordings. Usually extrasystoles were classified as rare, occasional, frequent and very frequent. Current publications were analyzed regarding the frequency and clinical significance or these arrhythmias, especially in in relation to prior myocardial infarction, ventricular dysfunction, atrial fibrillation and cerebro vascular events. Tables showing limits to define the severity of supraventricular and ventricular extrasystoles are included.

Procedural Characteristics, Safety, and Follow-up of Modified Right-Sided Approach for Cardioneuroablation.

BACKGROUND: Cardioneuroablation is one of the emerging therapies in vasovagal syncope. In this study, we present a simple method of cardioneuroablation performed via a rightsided approach, targeting anterior-right and right-inferior ganglionated plexi, along with procedural and follow-up data. METHODS: Patients who had underwent cardioneuroablation between March 2018 and September 2019 with vasovagal syncope in 2 clinics were enrolled in the study. All patients underwent radio-anatomically guided radiofrequency ablation targeting anterior-right ganglionated plexi and right-inferior ganglionated plexi. Syncope and symptom burden, 24-hour ambulatory electrocardiogram data at presentation, and at follow-up were assessed along with procedural data. RESULTS: A total of 23 patients underwent modified right-sided cardioneuroablation. Mean basal cycle length decreased significantly from 862.3 ± 174.5 ms at the beginning of the procedure 695.8 ± 152.1 ms following the final radiofrequency ablation (P < .001). Mean 24-hour ambulatory heart rate increased significantly from 66.4 ± 10.7 bpm at baseline to 80 ± 7.6 bpm at follow-up (P < .001). Only 1 patient had 1 episode of syncope following the procedure at the mean follow-up period of 10 ± 2.9 months. The same patient had recurrent presyncope. CONCLUSION: The right-sided cardioneuroablation approach was found to be an effective treatment for vasovagal syncope and may be regarded as a default initial cardioneuroablation technique.

Prospective arrhythmia surveillance after a COVID-19 diagnosis.

BACKGROUND: Cardiac arrhythmias have been observed among patients hospitalised with acute COVID-19 infection, and palpitations remain a common symptom among the much larger outpatient population of COVID-19 survivors in the convalescent stage of the disease. OBJECTIVE: To determine arrhythmia prevalence among outpatients after a COVID-19 diagnosis. METHODS: Adults with a positive COVID-19 test and without a history of arrhythmia were prospectively evaluated with 14-day ambulatory electrocardiographic monitoring. Participants were instructed to trigger the monitor for palpitations. RESULTS: A total of 51 individuals (mean age 42±11 years, 65% women) underwent monitoring at a median 75 (IQR 34-126) days after a positive COVID-19 test. Median monitoring duration was 13.2 (IQR 10.5-13.8) days. No participant demonstrated atrial fibrillation, atrial flutter, sustained supraventricular tachycardia (SVT), sustained ventricular tachycardia or infranodal atrioventricular block. Nearly all participants (96%) had an ectopic burden of <1%; one participant had a 2.8% supraventricular ectopic burden and one had a 15.4% ventricular ectopic burden. While 47 (92%) participants triggered their monitor for palpitation symptoms, 78% of these triggers were for either sinus rhythm or sinus tachycardia. CONCLUSIONS: We did not find evidence of malignant or sustained arrhythmias in outpatients after a positive COVID-19 diagnosis. While palpitations were common, symptoms frequently corresponded to sinus rhythm/sinus tachycardia or non-malignant arrhythmias such as isolated ectopy or non-sustained SVT. While these findings cannot exclude the possibility of serious arrhythmias in select individuals, they do not support a strong or widespread proarrhythmic effect of COVID-19 infection after resolution of acute illness.

Acompanhamento a longo prazo de paciente do sexo masculino com fibroma cardíaco assintomático / Long-Term follow-up of an asymptomatic man with a cardiac fibroma

Descreve-se o caso de um homem de 19 anos assintomático com fibroma de ventrículo esquerdo em acompanhamento por 15 anos, sem tratamento.(AU)

Here we describe a case of a 19-year-old asymptomatic man with a left ventricular fibroma on follow-up for 15 years with no treatment required.(AU)

Left atrial function analysis in patients with functional mitral regurgitation associated with dilated cardiomyopathy / Análise da função atrial esquerda em pacientes com insuficiência mitral funcional associada à miocardiopatia dilatada

BACKGROUND: Functional mitral regurgitation (FMR) is associated with dilated cardiomyopathy (DC), heart failure (HF), and worsening left atrial function (LAF). Patients with DC and FMR may present left atrial dysfunction resulting from both ventricular dysfunction and valve disease, but it is unknown whether the presence of valve disease will lead to greater LAF impairment. OBJECTIVE: This study aimed to evaluate the relationship between LAF parameters and FMR degree in patients with DC. METHODS: This cross-sectional observational study included 214 patients with DC, 46 without FMR (control group) and 168 with mild, moderate or severe FMR. An LAF analysis was performed by speckle tracking echocardiography (STE) and atrial volumetric variation. RESULTS: LAF analyzed by STE by means of reservoir strain, conduit strain and active contraction strain was reduced in the sample, with values of 14.3%, 8.49% and 5.92%, respectively. FMR degree was significantly associated with reservoir strain (0.27 ± 0.16 versus 0.15 ± 0.09; p < 0.001) and contraction strain (19.2 ± 7.3 versus 11.2 ± 2.7; p < 0.001). FMR was also associated with a reduced LAF assessed by volumetric analysis: total atrial emptying fraction of 0.51 ± 0.13 versus 0.34 ± 0.11 and active atrial emptying fraction of 0 .27 ± 0.16 versus 0.15 ± 0.09 (p < 0.001). CONCLUSION: In a population with DC, FMR was associated with reduced LAF assessed by STE and atrial volume variation.

FUNDAMENTO: A insuficiência mitral funcional (IMF) está associada à miocardiopatia dilatada (MD), à insuficiência cardíaca (IC) e à piora da função atrial esquerda (FAE). A FAE pode decair tanto pela disfunção ventricular quanto pela valvopatia, mas não se sabe se esta leva a um prejuízo maior da FAE. OBJETIVO: Avaliar a relação entre a piora de parâmetros de FAE com o grau de IMF, em pacientes com MD. MÉTODOS: Trata-se de estudo observacional transversal, que incluiu 214 pacientes com MD, sendo 46 sem IMF (controle) e 168 com IMF discreta, moderada ou grave. A análise da FAE foi realizada por ecocardiografia por speckle tracking (STE) e por variação volumétrica atrial. RESULTADOS: A FAE, analisada por STE­ por meio do strain de reservatório, conduto e contração ativa ­ encontrou-se reduzida na amostra, com valores respectivos de 14,3%, 8,49% e 5,92%. O grau de IMF associou-se significativamente com os valores do strain de reservatório (0,27±0,16 versus 0,15±0,09; p <0,001. CONCLUSÃO: Em uma população com MD, a presença de IMF associa-se à redução da FAE de reservatório e de contração, avaliada por STE e pela variação volumétrica atrial.

Identifying patients with atrial fibrillation recurrences after two pulmonary vein isolation procedures.

INTRODUCTION: Pulmonary vein isolation (PVI) is an important treatment for atrial fibrillation (AF). However, many patients need more than one procedure to maintain long-term sinus rhythm. Even after two PVIs some may suffer from AF recurrences. We aimed to identify characteristics of patients who fail after two PVI procedures. METHODS AND RESULTS: We included 557 consecutive patients undergoing a first PVI procedure with a second-generation 28 mm cryoballoon. Follow-up procedures were performed using radiofrequency ablation targeting reconnected PVs only. Recurrent AF was defined as any episode of AF lasting >30 s on ECG or 24 hour Holter monitoring performed at 3, 6 and 12 months post procedure. Mean age was 59.1±10.2 years, 383 (68.8%) were male, 448 (80.4%) had paroxysmal AF and the most common underlying condition was hypertension (36.6%). A total of 140/557 (25.1%) patients underwent redo procedure with PVI only. Of these patients 45 (32.4%) had recurrence of AF. These patients were comparable regarding age and sex to those in sinus rhythm after one or two procedures. Multivariate logistic regression showed that non-paroxysmal AF (OR 1.08 (95% CI 1.01 to 1.15), estimated glomerular filtration rate (OR 0.96, 95% CI 0.94 to 0.99), bundle branch block (OR 4.17, 95% CI 1.38 to 12.58), heart failure (OR 4.17, 95% CI 1.38 to 12.58) and Left Atrium Volume Index (OR 1.04, 95% CI 1.01 to 1.08) were associated with AF recurrence after two PVIs. The area under the curve for the identified risk factors was 0.74. CONCLUSIONS: Using a PVI-only approach, recurrence of AF after two AF ablation procedures is associated with more advanced underlying disease and persistent types of AF.

Effect of Continuous Electrocardiogram Monitoring on Detection of Undiagnosed Atrial Fibrillation After Hospitalization for Cardiac Surgery: A Randomized Clinical Trial.

Importance: Postoperative atrial fibrillation (POAF) occurring after cardiac surgery is associated with adverse outcomes. Whether POAF persists beyond discharge is not well defined. Objective: To determine whether continuous cardiac rhythm monitoring enhances detection of POAF among cardiac surgical patients during the first 30 days after hospital discharge compared with usual care. Design, Setting, and Participants: This study is an investigator-initiated, open-label, multicenter, randomized clinical trial conducted at 10 Canadian centers. Enrollment spanned from March 2017 to March 2020, with follow-up through September 11, 2020. As a result of the COVID-19 pandemic, enrollment stopped on July 17, 2020, at which point 85% of the proposed sample size was enrolled. Cardiac surgical patients with CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex) score greater than or equal to 4 or greater than or equal to 2 with risk factors for POAF, no history of preoperative AF, and POAF lasting less than 24 hours during hospitalization were enrolled. Interventions: The intervention group underwent continuous cardiac rhythm monitoring with wearable, patch-based monitors for 30 days after randomization. Monitoring was not mandated in the usual care group within 30 days after randomization. Main Outcomes and Measures: The primary outcome was cumulative AF and/or atrial flutter lasting 6 minutes or longer detected by continuous cardiac rhythm monitoring or by a 12-lead electrocardiogram within 30 days of randomization. Prespecified secondary outcomes included cumulative AF lasting 6 hours or longer and 24 hours or longer within 30 days of randomization, death, myocardial infarction, ischemic stroke, non-central nervous system thromboembolism, major bleeding, and oral anticoagulation prescription. Results: Of the 336 patients randomized (163 patients in the intervention group and 173 patients in the usual care group; mean [SD] age, 67.4 [8.1] years; 73 women [21.7%]; median [interquartile range] CHA2DS2-VASc score, 4.0 [3.0-4.0] points), 307 (91.4%) completed the trial. In the intent-to-treat analysis, the primary end point occurred in 32 patients (19.6%) in the intervention group vs 3 patients (1.7%) in the usual care group (absolute difference, 17.9%; 95% CI, 11.5%-24.3%; P < .001). AF lasting 6 hours or longer was detected in 14 patients (8.6%) in the intervention group vs 0 patients in the usual care group (absolute difference, 8.6%; 95% CI, 4.3%-12.9%; P < .001). Conclusions and Relevance: In post-cardiac surgical patients at high risk of stroke, no preoperative AF history, and AF lasting less than 24 hours during hospitalization, continuous monitoring revealed a significant increase in the rate of POAF after discharge that would otherwise not be detected by usual care. Studies are needed to examine whether these patients will benefit from oral anticoagulation therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02793895.

Association of Mitral Annular Disjunction With Cardiovascular Outcomes Among Patients With Marfan Syndrome.

Importance: Mitral annular disjunction (MAD) has received particular interest in patients with mitral valve prolapse, ventricular tachycardia, and sudden cardiac death. The clinical significance of MAD for patients with Marfan syndrome (MFS) remains largely unexplored. Objective: To define the prevalence of MAD and examine its association with cardiovascular outcomes and arrhythmia among patients with MFS. Design, Setting, and Participants: This retrospective, single-center cohort study included 142 patients with a diagnosis of MFS based on the revised Ghent criteria and a confirmed (likely) pathogenic variant in the FBN1 gene who underwent regular follow-up between January 1, 2004, and December 31, 2019. Main Outcomes and Measures: The presence of MAD was assessed by echocardiography, and the extent of MAD was categorized in tertiles. Patients also underwent resting electrocardiography and 24-hour Holter monitoring. Outcomes included aortic events (aortic dissection or prophylactic aortic surgery), arrhythmic events (defined as sustained ventricular tachycardia or sudden cardiac death), and mitral valve surgery. Results: A total of 142 patients (72 female patients [51%]; median age at first examination, 25 years [range, 2-64 years]) were evaluated. Forty-eight patients (34%) had MAD. Patients with MAD had larger aortic root z scores than patients without MAD (4.1 [interquartile range, 2.8-5.7] vs 3.0 [interquartile range, 1.8-4.0]; P < .001) and more often had mitral valve prolapse (34 of 48 [71%] vs 14 of 94 [15%]; P < .001), ventricular ectopy (14 of 33 [42%] vs 15 of 70 [21%]; P = .03), and nonsustained ventricular tachycardia (13 of 33 [39%] vs 12 of 70 [17%]; P = .01). During follow-up, aortic events occurred at similar rates among patients with vs without MAD (15 of 43 [35%] vs 21 of 84 [25%]; P = .24), but patients in the upper MAD tertile (>10 mm) showed a higher occurrence of aortic events compared with patients with MAD of 10 mm or smaller (9 of 15 [60%] vs 6 of 28 [21%]; P = .01). Patients with arrhythmic events (n = 5) and patients requiring mitral valve surgery (n = 7) were observed exclusively in the group displaying MAD. Conclusions and Relevance: This study suggests that MAD among patients with MFS is associated with the occurrence of arrhythmic events, a higher need for mitral valve intervention, and, among patients with extensive MAD, more aortic events. Cardiac imaging for patients with MFS should consider the assessment of MAD as a potential marker for adverse outcomes.

Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial.

BACKGROUND: To which extent atrial remodeling occurs before atrial fibrillation (AF) is unknown. OBJECTIVE: The PREventive left atrial appenDage resection for the predICtion of fuTure Atrial Fibrillation (PREDICT-AF) study investigated such subclinical remodeling, which may be used for risk stratification and AF prevention. METHODS: Patients (N = 150) without a history of AF with a CHA2DS2-VASc score of ≥2 at an increased risk of developing AF were included. The left atrial appendage was excised and blood samples were collected during elective cardiothoracic surgery for biomarker discovery. Participants were followed for 2 years with Holter monitoring to determine any atrial tachyarrhythmia after a 50-day blanking period. RESULTS: Eighteen patients (12%) developed incident AF, which was associated with increased tissue gene expression of collagen I (COL1A1), collagen III (COL3A1), and collagen VIII (COL8A2), tenascin-C (TNC), thrombospondin-2 (THBS2), and biglycan (BGN). Furthermore, the fibroblast activating endothelin-1 (EDN1) and sodium voltage-gated channel ß subunit 2 (SCN2B) were associated with incident AF whereas the Kir2.1 channel (KCNJ2) tended to downregulate. The plasma levels of COL8A2 and TNC correlated with tissue expression and predicted incident AF. A gene panel including tissue KCNJ2, COL1A1, COL8A2, and EDN1 outperformed clinical prediction models in discriminating incident AF. CONCLUSION: The PREDICT-AF study demonstrates that atrial remodeling occurs long before incident AF and implies future potential for early patient identification and therapies to prevent AF (ClinicalTrials.gov identifier NCT03130985).

Diagnosis and prevention of the vasodepressor type of neurally mediated syncope in Japanese patients.

We investigated circulatory dynamics in patients with vasodepressor type neurally mediated syncope (VT-NMS) by performing high-resolution Holter electrocardiography and a correlation analysis of changes in adenylate cyclase activity, blood pressure, and pulse during the head-up tilt test. Holter electrocardiography was performed for 30 patients. Adenylate cyclase activity was evaluated in lymphocytes from blood samples taken at rest and during the head-up tilt test. There was no change in autonomic nerve fluctuation during electrocardiography in VT-NMS patients, but our results showed a significant difference in blood pressure and adenylate cyclase activity between VT-NMS patients and healthy volunteers; the systolic blood pressure of VT-NMS patients decreased after 5 min, while at 10 min, the adenylate cyclase activity was the highest (0.53%) and the systolic blood pressure was the lowest (111.8 mm Hg). Pulse rates increased after 10 min. VT-NMS patients showed higher blood pressure, pulse rate, and adenylate cyclase activity during the tilt test than did healthy volunteers. In patients with syncope, standing for longer than 10 minutes may increase the risk of VT-NMS. From our results, we consider it likely that high systolic blood pressure and adenylate cyclase activity at rest cause fainting in VT-NMS patients. Our findings may be helpful for identifying individuals with a high risk of developing NMS in the healthy population.

Clinical characteristics and risk of arrhythmic events in patients younger than 12 years diagnosed with Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an inheritable disease with an increased risk of sudden cardiac death. Although several score systems have been proposed, the management of children with BrS has been inconsistently described. OBJECTIVE: The purpose of this study was to identify the characteristics, outcome, and risk factors associated with cardiovascular and arrhythmic events (AEs) in children younger than 12 years with BrS. METHODS: In this single-center case series, all children with spontaneous or drug/fever-induced type 1 Brugada electrocardiographic (ECG) pattern and younger than 12 years at the time of diagnosis were enrolled. RESULTS: Forty-three patients younger than 12 years at the time of diagnosis were included. The median follow-up was 3.97 years (interquartile range 2-12 years). In terms of first-degree atrioventricular block, premature beats, nonmalignant AEs, malignant AEs, and episodes of syncope, no significant differences were observed either between patients with spontaneous and drug/fever-induced type 1 Brugada ECG pattern or between female and male patients (except a significant difference between female and male patients for first-degree atrioventricular block). A higher incidence of malignant AEs was observed in patients with syncope (3 of 8 [37.5%] vs 0 of 35 [0%]; P = .005) than in patients without syncope. SCN5A mutations were associated with a higher occurrence of malignant AEs (3 of 14 [21.4%] vs 0 of 25 [0%]; P = .04) compared with no SCN5A mutations. CONCLUSION: A spontaneous type 1 Brugada ECG pattern is not associated with a higher incidence of syncope, first-degree atrioventricular block, premature beats, nonmalignant AEs, and malignant AEs than the drug/fever-induced type 1 Brugada ECG pattern. Syncope events are correlated with an increased incidence of malignant AEs. Moreover, SCN5A mutations are associated with a higher occurrence of malignant AEs.

Feasibility of P wave Centric Ambulatory Electrocardiogram Monitoring in Infants and Young Children.

P wave centric ambulatory electrocardiographic (ECG) monitoring has emerged as an important tool aiding the diagnosis of arrhythmias. However, their efficacy and user experience in infants and young children are not well established. A retrospective study was performed to detail clinical and user experience of ECG monitoring using the Carnation Ambulatory Monitor (CAM) patch (Bardy Diagnostics Inc., Seattle, WA) in patients less than 10 kg. Additionally, 2 different monitor locations (over the sternum and horizontal over the left axilla) were assessed to address the optimal placement in these patients. A total of 33 CAM reports from 25 patients, aged 0 to15 months were included in the study. Mean patient age was 4.2 months ± 5.0 and mean weight was 5.3 kg ± 2.4. Thirty-six percent of patients (9/25) had known congenital heart disease. Indications for monitoring included: tachyarrhythmia (15/33, 45%), bradyarrhythmia (6/33, 18%), ectopic rhythm (9/33, 27%), cardiac tumor (1/33, 1%), and prolonged QT interval (1/33, 1%). All CAM reports showed clear, identifiable P waves which were diagnostic and lead to changes in medical management for 30% of patients (e.g., medication adjustments or discharge from cardiology care). We found the upright placement over the sternum performed better than the horizontal placement over the left axilla for small infants and children less than 10 kg. A P wave centric single-lead ECG monitor is helpful in providing accurate diagnostics tracings in infants and small children aiding in their clinical management.

Screening for Atrial Fibrillation in the Older Population: A Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention. Objective: To evaluate 2 home-based AF screening interventions. Design, Setting, and Participants: This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices. Interventions: The control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods. Main Outcomes and Measures: With intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors. Results: Of the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%). Conclusions and Relevance: In this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard clinical outcomes are now needed to evaluate the potential benefits and harms of AF screening. Trial Registration: ClinicalTrials.gov Identifier: NCT02392754.