Iron therapy and severe arrhythmias in HFrEF: rationale, study design, and baseline results of the RESAFE-HF trial.

AIMS: The Iron Intravenous Therapy in Reducing the burden of Severe Arrhythmias in HFrEF (RESAFE-HF) registry study aims to provide real-word evidence on the impact of intravenous ferric carboxymaltose (FCM) on the arrhythmic burden of patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency (ID), and implanted cardiac implantable electronic devices (CIEDs). METHODS AND RESULTS: The RESAFE-HF (NCT04974021) study was designed as a prospective, single-centre, and open-label registry study with baseline, 3, 6, and 12 month visits. Adult patients with HFrEF and CIEDs scheduled to receive IV FCM as treatment for ID as part of clinical practice were eligible to participate. The primary endpoint is the composite iron-related endpoint of haemoglobin ≥ 12 g/dL, ferritin ≥ 50 ng/L, and transferrin saturation > 20%. Secondary endpoints include unplanned HF-related hospitalizations, ventricular tachyarrhythmias detected by CIEDs and Holter monitors, echocardiographic markers, functional status (VO2 max and 6 min walk test), blood biomarkers, and quality of life. In total, 106 patients with a median age of 72 years (14.4) were included. The majority were male (84.9%), whereas 92.5% of patients were categorized to New York Heart Association II/III. Patients' arrhythmic burden prior to FCM administration was significant-19 patients (17.9%) received appropriate CIED therapy for termination of ventricular tachyarrhythmia in the preceding 12 months, and 75.5% of patients have frequent, repetitive multiform premature ventricular contractions. CONCLUSIONS: The RESAFE-HF trial is expected to provide evidence on the effect of treating ID with FCM in HFrEF based on real-world data. Special focus will be given on the arrhythmic burden post-FCM administration.

The usability and effect of an mHealth disease management platform on the quality of life of patients with paroxysmal atrial fibrillation - The emPOWERD-AF study.

Atrial fibrillation (AF) is the most common arrhythmia. myAlgos is an mHealth disease management system consisting of physician-oriented platform and patient-oriented smartphone app. Our purpose was to assess the usability of myAlgos by physicians and patients and the effect of myAlgos on the quality of life (QoL) in patients with paroxysmal AF (PAF). Physicians rated the platform with the Post-Study System Usability Questionnaire (PSSUQ). Patients rated the app with the mHealth App Usability Questionnaire (MAUQ). The e-medicine Platform for Optimizing the Workflow in hEaRt Diseases (emPOWERD-AF) study investigated the effect of myAlgos in PAF patients randomized to full/control version. QoL was measured by the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) and 5-level EQ-5D (EQ-5D-5L) questionnaires. myAlgos got a PSSUQ score of 2.52 ± 0.36 by five physicians and a MAUQ score of 79.9% by 33 patients. In emPOWERD-AF, 80 patients were randomized 1:1 (58.1 ± 8.7 years, 66% male). The median AFEQT change at 6 months was +2.63% in full version users and -1.63% in controls (p < .001). The myAlgos platform and app were easy-to-use and improved QoL in patients.

Syncope without prodromes is associated with excessive plasma release of adenosine at the time of syncope during head-up tilt table test.

BACKGROUND: In syncopal patients without underlying structural disease, we sought to investigate the association of Adenosine Plasma Levels (ADP) with the clinical presentation of neurally mediated syncope (NMS) and the outcomes of Head-Up Tilt Table Test (HUTT) and Adenosine test (ADT). METHODS: We studied 124 patients with different clinical types of NMS, i.e., Vasovagal (VVS, n=58), non-prodromes (NPS, n=18), or situational syncope (SS, n=48), using a standard protocol including HUTT and ADT. During HUTT, ADP was measured in the supine position, at table tilting and in syncope. RESULTS: Baseline ADP did not differ among groups. ADP at syncope were higher in NPS (n=5) compared to VVS (n=20): 0.23 vs. 0.12 µΜ, p=0.03, and SS (n=22): 0.04 µΜ, p=0.02. In NPS, ADP increased from supine to syncope (n=5): 0.15 vs. 0.23 µΜ, p=0.04. In VVS, ADP increased only from supine to tilt position: 0.11 vs. 0.14 µΜ, p=0.02. In SS, ADP did not change during HUTT. In positive vasodepressor HUTT, ADP increased from supine to tilt position (p=0.002) and at syncope (p=0.01). In SS, 20.0% exhibited cardioinhibitory HUTT vs. 6.8% in other forms of syncope (p=0.04). In SS, 22.9% manifested positive ADT vs 6.6% in other types of syncope (p=0.012). CONCLUSION: The subset of NPS patients with positive HUTT, show excessive ADP release at the time of syncope. This may explain the lack of prodromes in this form of syncope. Such observations contribute to the understanding of distinct profiles of clinical forms of syncope and may differentiate the management approach accordingly.

Comparing efficacy and safety in catheter ablation strategies for atrial fibrillation: a network meta-analysis.

BACKGROUND: There is no consensus on the most efficient catheter ablation (CA) strategy for patients with atrial fibrillation (AF). The objective of this study was to compare the efficacy and safety of different CA strategies for AF ablation through network meta-analysis (NMA). METHODS: A systematic search of PubMed, Web of Science, and CENTRAL was performed up to October 5th, 2020. Randomized controlled trials (RCT) comparing different CA approaches were included. Efficacy was defined as arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of 6 months. RESULTS: In total, 67 RCTs (n = 9871) comparing 19 different CA strategies were included. The risk of recurrence was significantly decreased compared to pulmonary vein isolation (PVI) alone for PVI with renal denervation (RR: 0.60, CI: 0.38-0.94), PVI with ganglia-plexi ablation (RR: 0.62, CI: 0.41-0.94), PVI with additional ablation lines (RR: 0.8, CI: 0.68-0.95) and PVI in combination with bi-atrial modification (RR: 0.32, CI: 0.11-0.88). Strategies including PVI appeared superior to non-PVI strategies such as electrogram-based approaches. No significant differences in safety were observed. CONCLUSIONS: This NMA showed that PVI in combination with additional CA strategies, such as autonomic modulation and additional lines, seem to increase the efficacy of PVI alone. These strategies can be considered in treating patients with AF, since, additionally, no differences in safety were observed. This study provides decision-makers with comprehensive and comparative evidence about the efficacy and safety of different CA strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number: CRD42020169494 .

P-Wave Beat-to-Beat Analysis to Predict Atrial Fibrillation Recurrence after Catheter Ablation.

The identification of patients prone to atrial fibrillation (AF) relapse after catheter ablation is essential for better patient selection and risk stratification. The current prospective cohort study aims to validate a novel P-wave index based on beat-to-beat (B2B) P-wave morphological and wavelet analysis designed to detect patients with low burden AF as a predictor of AF recurrence within a year after successful catheter ablation. From a total of 138 consecutive patients scheduled for AF ablation, 12-lead ECG and 10 min vectorcardiogram (VCG) recordings were obtained. Univariate analysis revealed that patients with higher B2B P-wave index had a two-fold risk for AF recurrence (HR: 2.35, 95% CI: 1.24-4.44, p: 0.010), along with prolonged P-wave, interatrial block, early AF recurrence, female gender, heart failure history, previous stroke, and CHA2DS2-VASc score. Multivariate analysis of assessable predictors before ablation revealed that B2B P-wave index, along with heart failure history and a history of previous stroke or transient ischemic attack, are independent predicting factors of atrial fibrillation recurrence. Further studies are needed to assess the predictive value of the B2B index with greater accuracy and evaluate a possible relationship with atrial substrate analysis.

Comparing Efficacy and Safety in Catheter Ablation Strategies for Paroxysmal Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

Although catheter ablation (CA) is an established treatment for paroxysmal atrial fibrillation (PAF), there is no consensus regarding the most efficient CA strategy. The objective of this network meta-analysis (NMA) was to compare the efficacy and safety of different CA strategies for PAF. A systematic search was performed in PubMed, Web of Science, and CENTRAL until the final search date, 5 October 2020. Randomised controlled trials (RCT) comparing different CA strategies and methods for pulmonary vein isolation (PVI) were included. Efficacy was defined as lack of arrhythmia recurrence after CA and safety as any reported complication related to the procedure during a minimum follow-up time of six months. In total, 43 RCTs comparing 11 different CA strategies involving 6701 patients were included. The risk of recurrence was significantly decreased in comparison with PVI with radiofrequency only for the following treatments: PVI with adjuvant ablation (RR: 0.79, CI: 0.65-0.97) and PVI with sympathetic modulation (RR: 0.64, CI: 0.46-0.88). However, PVI with radiofrequency was superior to non-PVI strategies (RR: 1.65, CI: 1.2-2.26). No statistically significant difference was found in safety between different CA strategies. Concerning different PVI strategies, no difference was observed either in efficacy or in safety between tested strategies. This NMA suggests that different PVI strategies are generally similar in terms of efficacy, while PVI with additional ablation or sympathetic modulation may be more effective than PVI alone. This study provides decision-makers with insights into the efficacy and safety of different CA strategies.

Ultrasound-guided versus anatomic landmark-guided vascular access in cardiac electrophysiology procedures: A systematic review and meta-analysis.

INTRODUCTION: Electrophysiology (EP) procedures are nowadays the gold-standard method for tachyarrhythmia treatment with impressive success rates, but also with a considerable risk of complications, mainly vascular. A systematic review and meta-analysis was performed to evaluate the safety of ultrasound (US)-guided femoral vein access in EP procedures compared to the traditional anatomic landmark-guided method. METHODS: We searched Pubmed (MEDLINE), Embase, Web of Science, and Cochrane electronic databases for relevant entries, dated from January 1st, 2000 to June 30th, 2021. Only observational studies and randomized controlled trials were included in this analysis. Data extraction included study details, patient characteristics, procedure details, and all types of vascular complications. Complications were classified as major if any intervention, prolongation of hospitalization, or readmission was required. RESULTS: 9 studies (1 randomized controlled trial and 8 observational), with 7858 participants (3743 in the US-guided group, 4115 in the control group), were included in the meta-analysis. Overall vascular complication rates were significantly decreased in the US-guided group compared to the control group (1.2 versus 3.2%, RR = 0.38, 95% CI, 0.27-0.53), in all EP procedures. Sub-group analysis of AF ablation procedures yielded similar results (RR 0.41, 95% CI, 0.29-0.58, p < 0.00001). The event reduction effect was significant for both major and minor vascular complications. CONCLUSION: US-guided vascular access in EP procedures is associated with significantly reduced vascular complications, compared to the standard anatomic landmark-guided approach, regardless of procedure complexity.

Sex-related differences in plaque characteristics and endothelial shear stress related plaque-progression in human coronary arteries.

BACKGROUND AND AIMS: Clinical atherosclerosis manifestations are different in women compared to men. Since endothelial shear stress (ESS) is known to play a critical role in coronary atherosclerosis development, we investigated differences in anatomical characteristics and endothelial shear stress (ESS)-related plaque growth in human coronary arteries in men compared to women. METHODS: 1183 coronary arteries (male/female: 944/239) from the PREDICTION study were studied for differences in artery/plaque and ESS characteristics, and ESS-related plaque progression (6-10 months follow-up) among men and women and after stratification for age. All characteristics were derived from IVUS-based vascular profiling and reported per 3 mm-segments (13,030 3-mm-segments (male/female: 10,465/2,565)). RESULTS: Coronary arteries and plaques were significantly smaller in females compared to males; but no important differences were observed in plaque burden, ESS and rate of plaque progression. Change in plaque burden was inversely related to ESS (p<0.001) with no difference between women versus men (ß: -0.62 ± 0.13 vs -0.68 ± 0.05, p=0.62). However, stratification for age demonstrated that ESS-related plaque growth was more marked in young women compared to men (<55 years, ß: -2.02 ± 0.61 vs -0.33 ± 0.10, p=0.007), reducing in magnitude over the age-categories up till 75 years. CONCLUSIONS: Coronary artery and plaque size are smaller in women compared to men, but ESS and ESS- related plaque progression were similar. Sex-related differences in ESS-related plaque growth were evident after stratification for age. These observations suggest that although the fundamental processes of atherosclerosis progression are similar in men versus women, plaque progression may be influenced by age within gender.

Beat-to-Beat P-Wave Analysis Outperforms Conventional P-Wave Indices in Identifying Patients with a History of Paroxysmal Atrial Fibrillation during Sinus Rhythm.

Early identification of patients at risk for paroxysmal atrial fibrillation (PAF) is essential to attain optimal treatment and a favorable prognosis. We compared the performance of a beat-to-beat (B2B) P-wave analysis with that of standard P-wave indices (SPWIs) in identifying patients prone to PAF. To this end, 12-lead ECG and 10 min vectorcardiogram (VCG) recordings were obtained from 33 consecutive, antiarrhythmic therapy naïve patients, with a short history of low burden PAF, and from 56 age- and sex-matched individuals with no AF history. For both groups, SPWIs were calculated, while the VCG recordings were analyzed on a B2B basis, and the P-waves were classified to a primary or secondary morphology. Wavelet transform was used to further analyze P-wave signals of main morphology. Univariate analysis revealed that none of the SPWIs performed acceptably in PAF detection, while five B2B features reached an AUC above 0.7. Moreover, multivariate logistic regression analysis was used to develop two classifiers-one based on B2B analysis derived features and one using only SPWIs. The B2B classifier was found to be superior to SPWIs classifier; B2B AUC: 0.849 (0.754-0.917) vs. SPWIs AUC: 0.721 (0.613-0.813), p value: 0.041. Therefore, in the studied population, the proposed B2B P-wave analysis outperforms SPWIs in detecting patients with PAF while in sinus rhythm. This can be used in further clinical trials regarding the prognosis of such patients.

The impact of atrial mechanical function on age-dependent presentation of neurocardiogenic syncope.

BACKGROUND: The contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive. HYPOTHESIS: We assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences. METHODS: We assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age <35 (group A, n = 56) and >35 years (group B, n = 68). Echocardiographic indices were measured before head-up tilt test (HUTT). RESULTS: A total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m2 , p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p < .001) and LA peak strain rate (reservoir phase 1.83 ± 1.04 vs. 1.36 ± 0.96 1/s, p = .012, conduit phase 2.36 ± 1.25 vs. 1.36 ± 0.78 1/s, p = .001). Group A showed smaller minimum right atrial (RA) volume, better RA systolic function, superior left ventricular diastolic indices, and lower filling pressures. Group A patients were more likely to have >3 recurrences (82.0% vs. 50.1%, p < .05). CONCLUSIONS: Patients with younger age of NCS onset and more syncopal recurrences manifest smaller LA and RA dimensions with distinct patterns of systolic and diastolic function and better LA reservoir and contraction properties. These findings may indicate an increased susceptibility to preload reduction, thereby triggering the NCS mechanism.

Novel Lesional Transcriptional Signature Separates Atherosclerosis With and Without Diabetes in Yorkshire Swine and Humans.

[Figure: see text].

Is the Adenosine Test Obsolete in the Clinical Assessment of Syncope of Unknown Origin?

Syncope is a common clinical condition affecting 50% of the general population; however, its exact pathophysiology and underlying mechanisms remain elusive. The adenosine test (ADT) has been proposed as a complementary diagnostic test in the work-up of syncope of unknown origin aiming to further elucidate the underlying pathogenetic mechanism of spontaneous syncope. Although ADT has not been endorsed by the recent European Society of Cardiology guidelines on syncope management, the use of a quick, safe and non-invasive test which can contribute to an accurate diagnosis and rationalised therapy, may deserve further consideration. This review summarises the evidence on the role of ADT in the investigation and management of syncope of unknown origin and highlights future perspectives in this area. The authors also analyse the current challenges and research targets on adenosine plasma levels and its receptors due to the involvement of the adenosine pathway in the ADT response.

Excessive Supraventricular Ectopic Activity and Adverse Cardiovascular Outcomes: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality. RECENT FINDINGS: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately. RESULTS: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70-2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24-4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25-2.07). Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes.

Impact of Radiofrequency Ablation and Antiarrhythmic Medications on the Quality of Life of Patients with Supraventricular Tachycardias: Preliminary Validation of the Greek Version of the Umea22 (U22) Questionnaire.

OBJECTIVE: This study aims to (i) translate, culturally adapt, and preliminarily validate the arrhythmia-specific Umea22 (U22) questionnaire and (ii) assess the impact of radiofrequency (RF) ablation and medical treatment on the quality of life of patients with supraventricular tachycardias (SVTs). METHODS: A total of 140 patients with atrioventricular nodal re-entry tachycardia (AVNRT) and atrioventricular re-entry tachycardia (AVRT) were enrolled in the study. Of these, 100 patients underwent RF ablation (group A) and 40 patients were managed with antiarrhythmic medications (group B). Health-related quality of life (HRQoL) was assessed for both groups using the Short Form-36 Health Survey (SF-36) and the arrhythmia-specific Umea22 (U22) questionnaire at baseline and 3-month follow-up. Exploratory and confirmatory factor analyses were performed to assess the validity of the U22 questionnaire. Univariate comparisons of HRQoL scores between study timepoints and multivariate regression analyses adjusting for baseline confounders were conducted. RESULTS: The factor analysis of the U22 questionnaire yielded a six-factor model ("burden of spells"; "heart contractility"; "character of spells"; "general/non-specific feeling"; "other specific somatic symptoms"; "fear") with acceptable fit results. Patients of group A showed significant improvement in all SF-36 and U22 scores at 3 months' follow-up compared to baseline (all p<0.05). Patients of group B presented deterioration of the total SF-36 score (p=0.001) and improvement of certain U22 measures, namely, well-being (p=0.004), heartbeat speed, and intensity during arrhythmia spells (p<0.0001 for both measures) at 3 months' follow-up, compared to baseline. Employment status, male sex, and urban residence emerged as important predictors. CONCLUSION: The Greek version of the U22 questionnaire is a valid tool to assess SVT-related symptoms. RF ablation appears to exert more pronounced beneficial outcomes on HRQoL of patients with SVTs compared to medical treatment. Prompt referral of patients with SVTs to specialist centers may favorably affect their quality of life and should be encouraged.

ARCOCT: Automatic detection of lumen border in intravascular OCT images.

BACKGROUND AND OBJECTIVE: Intravascular optical coherence tomography (OCT) is an invaluable tool for the detection of pathological features on the arterial wall and the investigation of post-stenting complications. Computational lumen border detection in OCT images is highly advantageous, since it may support rapid morphometric analysis. However, automatic detection is very challenging, since OCT images typically include various artifacts that impact image clarity, including features such as side branches and intraluminal blood presence. This paper presents ARCOCT, a segmentation method for fully-automatic detection of lumen border in OCT images. METHODS: ARCOCT relies on multiple, consecutive processing steps, accounting for image preparation, contour extraction and refinement. In particular, for contour extraction ARCOCT employs the transformation of OCT images based on physical characteristics such as reflectivity and absorption of the tissue and, for contour refinement, local regression using weighted linear least squares and a 2nd degree polynomial model is employed to achieve artifact and small-branch correction as well as smoothness of the artery mesh. Our major focus was to achieve accurate contour delineation in the various types of OCT images, i.e., even in challenging cases with branches and artifacts. RESULTS: ARCOCT has been assessed in a dataset of 1812 images (308 from stented and 1504 from native segments) obtained from 20 patients. ARCOCT was compared against ground-truth manual segmentation performed by experts on the basis of various geometric features (e.g. area, perimeter, radius, diameter, centroid, etc.) and closed contour matching indicators (the Dice index, the Hausdorff distance and the undirected average distance), using standard statistical analysis methods. The proposed method was proven very efficient and close to the ground-truth, exhibiting non statistically-significant differences for most of the examined metrics. CONCLUSIONS: ARCOCT allows accurate and fully-automated lumen border detection in OCT images.

Updates in Cardiac Resynchronization Therapy for Chronic Heart Failure: Review of Multisite Pacing.

PURPOSE OF REVIEW: Cardiac resynchronization therapy (CRT) reduces the morbidity and mortality of patients with left ventricular (LV) systolic dysfunction and intra-ventricular conduction delay. However, its clinical outcomes are heterogeneous and not all patients show a beneficial response. Multisite pacing (MSP), by stimulating the myocardium from more than one locations, is a potential therapeutic option in patients requiring CRT. This article provides a current update in the methods and outcomes of MSP, as well as in challenges in this field and opportunities for further research and development. RECENT FINDINGS: MSP can be delivered either with multiple leads or with quadripolar LV leads which can stimulate the LV from two separate sites. Initial results are promising but not always consistent across studies. Larger patient subgroups and longer follow-up duration are required for more conclusive evaluation of MSP. Routine use of MSP in clinical practice cannot be advocated at present. In selected patient subgroups, however, MSP could be considered. Newer devices and expanding knowledge are expected to facilitate the more widespread implementation of MSP and the assessment of its effects in the clinical outcomes of CRT.

Evolving understanding of the heterogeneous natural history of individual coronary artery plaques and the role of local endothelial shear stress.

PURPOSE OF REVIEW: Anatomic and morphologic features of high-risk coronary plaque have been identified by novel imaging modalities, but it has been less clear which ostensibly high-risk plaques will actually destabilize and cause a new cardiac event. Different plaques with different morphologies coexist within the same artery, but the impact of this heterogeneity on the natural history of coronary artery disease has not been extensively investigated. RECENT FINDINGS: Coronary plaques exhibit remarkable heterogeneity of local morphological and blood-flow patterns, including endothelial shear stress (ESS), along their longitudinal axis, with important implications for the heterogeneous natural history of coronary disease. The natural history of individual plaques is considerably divergent, with most plaques, even ostensibly high-risk plaques, becoming quiescent and only a minority progressing to destabilize and precipitate a new clinical event. Local areas of proinflammatory low ESS appear to be an important condition for plaque destabilization. SUMMARY: Characterization of an individual atherosclerotic plaque based on a snapshot of morphological features at a specific location, such as the minimal lumen diameter, may not be sufficiently comprehensive to accurately reflect the risk associated with that plaque. A detailed assessment of both anatomical and functional pathobiologic characteristics in the longitudinal plaque dimension may enhance our understanding of atherosclerosis progression and improve the management of individual patients with coronary artery disease.