Low-voltage areas in the left atrium predict atrial fibrillation recurrence after catheter ablation and are associated with adverse outcomes like death, heart failure, and stroke. Detecting low-voltage areas (LVAs) typically requires invasive procedures, highlighting the need for a simple, minimally invasive marker. Vasoactive intestinal peptide (VIP), a neuropeptide released during parasympathetic stimulation, affects electrophysiological remodeling in atrial fibrillation. We hypothesized that serum VIP could serve as a biomarker for detecting LVAs in these patients.

This prospective, cross-sectional study was conducted at Hokkaido University Hospital between August 2021 and September 2023. We included 108 patients with atrial fibrillation scheduled for catheter ablation. Blood samples were collected during ablation to measure VIP using an ELISA. Electroanatomical mapping identified LVAs, defined as regions with bipolar voltage ≤0.5 mV and occupying >5% of the left atrial surface. Statistical analyses evaluated the relationship between VIP and LVAs. Fifty-one patients (47%) had LVAs, with significantly higher serum VIP levels than those without (335.1 versus 247.7 pg/mL, P<0.001). VIP levels and female sex were statistically significant factors of LVAs. Adding VIP to the existing score significantly improved its discrimination (area under the curve: 0.784 versus 0.707, P<0.001).

Serum VIP levels are higher in patients with atrial fibrillation with LVAs, suggesting its potential as a noninvasive biomarker for detecting these areas and improving clinical management.

Characterizing atrial fibrillation (AF) substrate can guide ablation strategies.

A novel parameter, peak frequency (PF), was evaluated in its ability to characterize the substrate in AF.

Patients undergoing persistent AF ablation were included. Patients had omnipolar voltage (OV) and PF maps in AF and bipolar voltage (BV) maps in sinus rhythm (SR) at pacing intervals of 600 and 250 ms. PF was evaluated at sites of fixed remodeling (low voltage zones [LVZs] across all maps), functional remodeling (LVZs in AF OV and SR BV 250 ms maps) and non-LVZs. PF was defined as the highest frequency detected in the electrogram.

In 40 patients, the average voltage in AF OV maps differed significantly from that in SR BV 600 ms maps (0.49±0.76 mV in AF OV vs 1.12±0.97 mV SR BV 600 ms; P<.001) but not SR BV 250 ms maps (0.49±0.76 mV in AF OV vs 0.52±0.84 mV SR BV 250 ms; P=.10). PFs of ≥244 and ≤214 Hz were predictive of non-LVZs (odds ratio [OR] 3.91; P<.001) with an area under the curve (AUC) of 0.71 and of fixed remodeling (OR 17.67; P<.001) with an AUC of 0.90, respectively. A PF between 215 and 236 Hz was predictive of functional remodeling (OR 2.83; 95% confidence interval 2.71-2.95; P<.001) with an AUC of 0.76. A majority of LVZs identified only in AF OV maps exhibited PF compatible with that seen in non-LVZs, suggesting that PF analysis can pinpoint potential overestimations of LVZs.

PF can effectively discern between sites of fixed remodeling, functional remodeling, and potential overestimations of LVZs. PF may thereby aid in better characterization of the substrate in AF.

Background: Chronic liver disease (CLD) and cirrhosis contribute to approximately 2 million deaths annually, with primary causes including alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and chronic hepatitis B and C infections. Among these, MASLD has emerged as a significant global health concern, closely linked to metabolic disorders and a leading cause of liver failure and transplantation. Objective: This review aims to highlight the interplay between cirrhosis and cardiac dysfunction, emphasizing the pathophysiology, diagnostic criteria, and management of cirrhotic cardiomyopathy (CCM). Methods: A comprehensive literature review was conducted to evaluate the hemodynamic and structural cardiac alterations in cirrhosis. Results: Cirrhosis leads to portal hypertension and systemic inflammation, contributing to CCM, which manifests as subclinical cardiac dysfunction, impaired contractility, and electrophysiological abnormalities. Structural changes, such as increased left ventricular mass, myocardial fibrosis, and ion channel dysfunction, further impair cardiac function. Vasodilation in the splanchnic circulation reduces peripheral resistance, triggering compensatory tachycardia, while the activation of the renin-angiotensin-aldosterone system (RAAS) promotes fluid retention and increases cardiac preload. Chronic inflammation and endotoxemia exacerbate myocardial dysfunction. The 2005 World Congress of Gastroenterology (WCG) and the 2019 Cirrhotic Cardiomyopathy Consortium (CCC) criteria provide updated diagnostic frameworks that incorporate global longitudinal strain (GLS) and tissue Doppler imaging (TDI). Prolonged QT intervals and arrhythmias are frequently observed. Managing heart failure in cirrhotic patients remains complex due to intolerance to afterload-reducing agents, and beta-blockers require careful use due to potential systemic hypotension. The interaction between CCM and major interventions, such as transjugular intrahepatic portosystemic shunt (TIPS) and orthotopic liver transplantation (OLT), highlights the critical need for thorough preoperative cardiac evaluation and vigilant postoperative monitoring. Conclusions: CCM is a frequently underdiagnosed yet significant complication of cirrhosis, impacting prognosis, particularly post-liver transplantation. Early identification using echocardiography and thorough evaluations of arrhythmia risk in cirrhotic patients are critical for optimizing management strategies. Future research should focus on targeted therapeutic approaches to mitigate the cardiac burden in cirrhotic patients and improve clinical outcomes.

Emerging evidence underscores the impact of circadian rhythms on cardiovascular processes, particularly in conditions such as hypertension, myocardial infarction, and heart failure, where circadian rhythm disruptions are linked to disease progression and adverse clinical outcomes. Circadian clock proteins are intricately linked to myocardial electrophysiological remodeling and epigenetic pathways associated with arrhythmias in heart failure. In the context of heart failure, circadian clock dysregulation leads to electrophysiological remodeling in the cardiomyocytes, which can precipitate life-threatening arrhythmias such as ventricular tachycardia (VT) and ventricular fibrillation (VF). This dysregulation may be influenced by environmental factors, such as diet and exercise, as well as genetic factors. Moreover, epigenetic modifications in heart failure have been implicated in the regulation of genes involved in cardiac hypertrophy, fibrosis, and inflammation. The interplay between circadian clock proteins, myocardial electrophysiological remodeling, and epigenetic pathways in heart failure-related arrhythmias is complex and multifaceted. Further research is needed to elucidate how these processes interact and contribute to the development of arrhythmias in heart failure patients. This review aims to explore the connections between circadian rhythms, myocardial electrophysiology, and arrhythmias related to heart failure, with the goal of identifying potential therapeutic targets and interventions that may counteract the adverse effects of circadian disruptions on cardiovascular health.

Abnormal P wave terminal force in lead V1 (PTFV1) has been associated with adverse outcomes in various cardiovascular conditions. However, the potential role of PTFV1 in patients with left ventricular noncompaction (LVNC) has not been reported. Therefore, this study aims to investigate the prevalence of PTFV1 in patients with LVNC and explore its possible association with abnormalities in both the left atrium (LA) and left ventricle (LV).

From January 2016 to December 2017, 93 patients diagnosed with LVNC via cardiovascular magnetic resonance (CMR) were enrolled in the study. Clinical, echocardiographic, CMR, and electrocardiogram data were retrospectively collected and analyzed independently.

The mean age of the 93 patients at diagnosis was 44.3 ± 13.9 years, with 64.5 % being male. Abnormal PTFV1 was present in 23.6 % of the patients. Those with abnormal PTFV1 had significantly higher rates of NYHA functional class III or IV (86.4 % vs. 19.7 %, p < 0.001), LV thrombus (9.0 % vs. 4.2 %, p = 0.049), and late gadolinium enhancement (63.6 % vs. 33.8 %, p = 0.013). These patients also had significantly greater mitral regurgitation grades, larger LA and LV volume indices, and lower LV ejection fraction (LVEF). Receiver operating characteristic curve analysis showed moderate-to-high area under the curve (AUC) values (ranging from 0.72 to 0.83) for various indices in identifying abnormal PTFV1, with LVEF showing the highest AUC of 0.83. Binary logistic regression identified LVEF as the only independent factor associated with abnormal PTFV1 (OR = 0.89, p = 0.003).

Abnormal PTFV1, observed in approximately one-quarter of LVNC patients, is linked to more severe cardiac remodeling and dysfunction, and its presence can be predicted by a reduced LVEF.

Convincing evidence for the efficacy of ablation as first-line therapy in paroxysmal AF (PAF) and its clear superiority to medical therapy for rhythm control in both PAF and persistent AF (PsAF) has generated considerable interest in the optimal timing of ablation. Based on this data, there is a widespread view that the principle of 'the earlier the better' should be generally applied. However, the natural history of AF is highly variable and non-linear, and for this reason, it is difficult to be emphatic that all patients are best served by ablation early after their initial AF episodes. Sufficient evidence exists to indicate a conservative approach is reasonable in patients with infrequent and non-progressive episodes (i.e. absence of progressive increase in burden culminating in PsAF) in whom symptoms remain mild and well-controlled. A conservative management phase should be marked by assiduous attention to risk factor modification, changes in frequency and duration of AF episodes, and patient preferences. If and when AF does begin to progress, accumulating evidence indicates that early ablation accompanied by ongoing attention to risk factors provides the best outcomes.

Electrographic flow (EGF) mapping allows for the visualization of global atrial wavefront propagations. One mechanism of initiation and maintenance of atrial fibrillation (AF) is stimulation from EGF-identified focal sources that serve as driver sites of fibrillatory conduction. Electrographic flow consistency (EGFC) further quantifies the concordance of observed wavefront patterns, indicating that a healthier substrate shows more organized wavefront propagation and higher EGFC. Freedom from AF (FFAF) recurrence has accordingly been shown to be higher in patients with ablated vs. unablated sources and with high vs. low EGFC.

(1) Measure FFAF across EGF-derived phenotypes in patients enrolled in the AF-FLOW Global Registry; (2) determine if a relationship exists between EGFC and percentage of healthy voltage as measured from bipolar voltage maps.

The AF-FLOW Global Registry is a multicenter, prospective study of 25 all-comer AF patients who underwent concomitant high-density bipolar voltage mapping with a 16-electrode grid mapping catheter and EGF mapping with a 64-pole basket catheter. The EGF algorithm detects extra-pulmonary vein sources as origins of excitation from a singularity of divergent flow vectors and was used to localize RF ablation targets. Overall, EGFC per atrium was also computed as the average of the modulus of individual EGF vectors, where the vector length represents the consistency of flow patterns. Patients were then assigned phenotypes on the basis of source presence or absence and EGFC, and rates of FFAF at 1-year were compared across the four resulting phenotypes. Atrial EGFC was also compared to the percentage of healthy tissue determined by bipolar voltage mapping.

Patients with paroxysmal AF had higher FFAF than persistent AF (PeAF) and long-standing PeAF patients; patients receiving de novo ablation had higher FFAF than those receiving redo ablation. Patient phenotyping revealed that those with high EGFC had higher FFAF than those with low EGFC (p = 0.015). Atrial EGFC was also correlated to the percent of high voltage tissue across all patients (r = 0.651, p < 0.0001).

EGF mapping provides insights into the mechanistic nature of AF and the atrial health of the underlying substrate. Therefore, further studies are needed to develop phenotype-specific treatments for the disease.

ClinicalTrials.gov identifier: NCT05481359.

End-stage heart failure (HF) accounts for 1% to 10% of all HF cases. It is frequently associated with coexistent atrial fibrillation due in part to structural changes related to altered hemodynamics, increased wall stress, and neurohormonal activation. The treatment remains challenging because of frequent atrial remodeling, comorbidities, and high recurrence rates. Studies have found no benefit of medical rhythm control compared with rate control. However, recent data suggest that catheter ablation might be associated with a reduction in HF symptomatology and all-cause mortality. Alternative treatment options including AV nodal ablation are available for refractory cases, but should not delay urgent heart transplantation.

Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation.

We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials through August 2024. Pairwise, prognostic, and reconstructed time-to-event data meta-analyses were conducted using R V. 4.3.1. Our primary end point was time to first AF recurrence, with secondary end points of all-cause mortality, tamponade, stroke, and heart failure.

Our cohort included 23 studies with 43 711 patients. Shorter DAT was significantly associated with reduced AF recurrence across both paroxysmal and persistent AF subgroups (P<0.01). There was a significant decrease in benefit for paroxysmal AF over time and a slight decrease in benefit for persistent AF over time. However, the benefit remained significant in both over time. DAT per year was significantly associated with a 10% increased risk of AF recurrence. Reconstructed Kaplan-Meier analysis showed that DAT >1 year was significantly associated with a 70% increased risk of AF recurrence in paroxysmal AF and 30% in persistent AF. DAT ≤1 year was significantly associated with decreased all-cause mortality (P<0.01) and showed a trend toward an association with a lower incidence of stroke (P=0.08). However, there was no significant difference in heart failure between DAT ≤1 year and DAT >1 year.

Early ablation is more beneficial in paroxysmal AF, with a notable decrease in benefit over time, while in persistent AF, the benefit remains significant but slightly decreases over time. Shorter DAT was significantly associated with decreased all-cause mortality and showed a trend toward an association with a lower incidence of stroke.

URL: https://www.crd.york.ac.uk/prospero/display_record.php?; Unique identifier: CRD42024525542.

Persistent atrial fibrillation (AF) patients with tachycardia-induced cardiomyopathy (TIC) undergoing catheter ablation have similar or even better outcomes than patients without TIC. Data regarding atrial substrate remodeling are scarce in cases of TIC. We assessed regional distribution of left atrial (LA) bipolar voltage, the extent of low-voltage zones (LVZs), and outcomes of voltage-guided ablation in AF patients with and without TIC.

In all, 139 patients with persistent AF presenting for a first voltage-guided catheter ablation were enrolled, 61 with TIC and 78 with structurally normal hearts. LA voltage maps were obtained using a 3-dimensional electroanatomical mapping system in sinus rhythm. LVZ was defined as <0.5 mV. Compared with non-TIC patients, TIC patients had a lower indexed LA volume (median [interquartile range] 58.6 [50.6-68.7] vs. 63.4 [60.1-76.1] mL/m2; P<0.01) and higher LA voltage (2.3 [1.5-2.8] vs. 1.7 [1-2.6] mV; P=0.02). LVZs were less frequently found in patients with than without TIC (8 [13.1%] vs. 30 [39%]; P<0.01). There was no significant difference in atrial tachyarrhythmia (AT)-free survival rate over a 36-month follow-up between the 2 groups (log-rank test, P=0.176). No predictor of AT recurrence was identified.

TIC patients exhibit less LA substrate remodeling with a smaller LA volume, higher bipolar voltage, and fewer LVZs than non-TIC patients. They have a similar favorable outcome after a single procedure.

Atrial flutter (AFL), defined as macro-re-entrant atrial tachycardia, is associated with debilitating symptoms, stroke, heart failure, and increased mortality. AFL is classified into typical, or cavotricuspid isthmus (CTI)-dependent, and atypical, or non-CTI-dependent. Atypical AFL is a heterogenous group of re-entrant atrial tachycardias that most commonly occur in patients with prior heart surgery or catheter ablation. The ECG pattern is poorly predictive of circuit anatomy but may still provide mechanistic insight. AFL is difficult to manage medically and catheter ablation is the preferred treatment for most patients. Recent progress in technology and clinical electrophysiology has led to detailed characterization of re-entry circuits and effective ablation strategies. Combined activation and entrainment mapping are key to identifying the re-entry circuit. The presence of a slow-conducting isthmus, localized re-entry, dual-loop re-entry or bystander loops may lead to misleading activation maps but can be identified by electrogram examination and entrainment mapping. In the occasional patient without inducible AFL, substrate mapping in sinus rhythm may be a viable strategy. Long-term ablation success requires the creation of a transmural continuous lesion across a critical component of the re-entry circuit. Procedural endpoints include bidirectional conduction block across linear lesions and non-inducibility of atrial tachycardia. The present review discusses the epidemiology, mechanisms, ECG characteristics, electrophysiological characterization, and catheter ablation of atypical AFL.

Arrhythmias are divided into supraventricular and ventricular, depending on where they originate [...].

The innovative peak frequency mapping facilitates the quantification of electrogram sharpness. However, reference values for normal atrial tissue are currently undefined. In this study, we explored the distribution of peak frequency and omnipolar peak-to-peak voltage (V-max) in a normal heart.

Twenty-two patients with structurally normal heart were included. Either the right atrium (RA) and superior vena cava (SVC) or the left atrium (LA) and pulmonary veins (PVs) were mapped during sinus rhythm.

In total, 13,654 points in the RA and 4143 points in the SVC from 15 patients and 4662 points in the LA and 2761 points in PVs from 7 patients were analyzed. The correlation between peak frequency and V-max was weak (R = 0.223). The median peak frequency was larger in the SVC than in the RA (441 [358-524] Hz vs. 358 [291-441] Hz, P < 0.0001) and in PVs than in the LA (346 [253-441] Hz vs. 323 [262-397] Hz, P < 0.0001). Conversely, the median V-max was smaller in the SVC than in the RA (1.96 [0.77-3.75] mV vs. 4.11 [2.10-6.83] mV, P < 0.0001) and in PVs than in the LA (1.16 [0.33-3.17] mV vs. 4.42 [2.63-6.84] mV, P < 0.0001). More than 95% of peak frequencies were > 174 Hz in the RA and > 185 Hz in the LA, and > 95% of V-maxes were > 0.52 and > 1.07 mV in the RA and LA, respectively.

Given the limited correlation between peak frequency and V-max, and recognizing their potential to provide distinct information, they can be used complementarily. Employing these parameters to extract varied insights can provide comprehensive understandings of tissue characteristics.

Electrographic flow (EGF) mapping reconstructs atrial electrical wavefront propagation, potentially revealing sources of atrial fibrillation (AF). Electrographic flow consistency (EGFC) measures the concurrence of wavefront patterns and may provide insights into atrial substrate health. This study aimed to compare EGF patterns during atrial fibrillation (AF) with sinus rhythm (SR) and explore the correlation between EGFC and regional bipolar voltage.

In this single-center, prospective study, AF patients underwent mapping of the atria using bipolar voltage and EGF mapping. Mapping was performed during both AF and SR using a 16-electrode grid catheter (bipolar mapping) and a 64-pole basket catheter (EGF mapping). EGFC was computed as the average modulus of individual EGF vectors, reflecting flow pattern consistency.

Ten patients were enrolled. EGF identified 11 sources with a mean source activity of 32 ± 9% during AF. Eight out of eleven sources in AF converted to passive "sinks" when mapped in SR. EGFC was significantly lower during AF compared to SR (0.74 ± 0.14 vs 1.0 ± 0.11 AUs, P < 0.01), consistent with EGFC quantifying the more chaotic wavefront propagation during arrhythmia. No spatial correlation between areas of high EGFC during AF and SR was observed. EGFC correlated with bipolar voltage across rhythms and atria (r = 0.647, P < 0.0001).

EGF patterns varied by rhythm with AF showing lower EGFC values. EGFC correlated with bipolar voltage across rhythms and atria, suggesting its potential as an atrial myopathy marker akin to high-density voltage mapping and offering insights into atrial substrate health. Trial registration ClinicalTrials.gov Identifier: NCT06260670.

During catheter ablation of post-infarct ventricular tachycardia (VT), substrate mapping is used when VT is non-inducible or poorly tolerated. Substrate mapping aims to identify regions of slowly conducting myocardium (borderzone) within and surrounding myocardial scar for ablation. Historically, these tissue types have been identified using bipolar voltage mapping, with areas of low bipolar voltage (<0.50 mV) defined as scar, and areas with voltages between 0.50 mV and 1.50 mV as borderzone. In the era of high-density mapping, studies have demonstrated slow conduction within areas of bipolar voltage <0.50 mV, suggesting that this historical cut-off is outdated. While electrophysiologists often adapt voltage cut-offs to account for this, the optimal scar-borderzone threshold is not known. In this review, we discuss dynamic voltage mapping, a novel substrate mapping technique we have developed, which superimposes data from both activation and voltage maps, to help delineate the post-infarct VT circuit through identification of the optimal scar-borderzone voltage threshold.

Paroxysmal atrial fibrillation is a common arrhythmia, and its development process and prediction of the degree of atrial fibrosis are of great significance for treatment and management. Optical imaging technology provides a new means for non-invasive observation of atrial electrical activity. The aim of this study is to investigate the predictive effect of sinus node recovery time on the degree of atrial fibrosis in patients with paroxysmal atrial fibrillation, and to provide a basis for the application of optical imaging technology in the study of atrial fibrosis. The study collected clinical and optical imaging data from a group of patients with paroxysmal atrial fibrillation, and used statistical analysis methods to investigate the relationship between sinus node recovery time and the degree of atrial fibrosis. The research results indicate that there is a significant correlation between the recovery time of the sinus node and the degree of atrial fibrosis, that is, there is a positive correlation between the prolonged recovery time of the sinus node and the aggravation of atrial fibrosis. SNRT can serve as an effective indicator for evaluating atrial matrix and can be applied to predict recurrence after catheter ablation of paroxysmal atrial fibrillation. Shortening SNRT through catheter ablation can become an important predictor of effective catheter ablation.

As atrial fibrillation (AF) progresses from initial paroxysmal episodes to the persistent phase, maintaining sinus rhythm for an extended period through pharmacotherapy and catheter ablation becomes difficult. A major cause of the deteriorated treatment outcome is the atrial structural and electrophysiological heterogeneity, which AF itself can exacerbate. This heterogeneity exists or manifests in various dimensions, including anatomically segmental structural features, the distribution of histological fibrosis and the autonomic nervous system, sarcolemmal ion channels, and electrophysiological properties. All these types of heterogeneity are closely related to the development of AF. Recognizing the heterogeneity provides a valuable approach to comprehending the underlying mechanisms in the complex excitatory patterns of AF and the determining factors that govern the seemingly chaotic propagation. Furthermore, substrate modification based on heterogeneity is a potential therapeutic strategy. This review aims to consolidate the current knowledge on structural and electrophysiological atrial heterogeneity and its relation to the pathogenesis of AF, drawing insights from clinical studies, animal and cell experiments, molecular basis, and computer-based approaches, to advance our understanding of the pathophysiology and management of AF.

Atrial high-rate episodes (AHREs) are frequent in patients with cardiac implantable electronic devices. A decrease in device-detected P-wave amplitude may be an indicator of periods of increased risk of AHRE.

The objective of this study was to assess the association between P-wave amplitude and AHRE incidence.

Remote monitoring data from 2579 patients with no history of atrial fibrillation (23% pacemakers and 77% implantable cardioverter-defibrillators, of which 40% provided cardiac resynchronization therapy) were used to calculate the mean P-wave amplitude during 1 month after implantation. The association with AHRE incidence according to 4 strata of daily burden duration (≥15 minutes, ≥6 hours, ≥24 hours, ≥7 days) was investigated by adjusting the hazard ratio with the CHA2DS2-VASc score.

The adjusted hazard ratio for 1-mV lower mean P-wave amplitude during the first month increased from 1.10 (95% confidence interval [CI], 1.05-1.15; P < .001) to 1.18 (CI, 1.09-1.28; P < .001) with AHRE duration strata from ≥15 minutes to ≥7 days independent of the CHA2DS2-VASc score. Of 871 patients with AHREs, those with 1-month P-wave amplitude <2.45 mV had an adjusted hazard ratio of 1.51 (CI, 1.19-1.91; P = .001) for progression of AHREs from ≥15 minutes to ≥7 days compared with those with 1-month P-wave amplitude ≥2.45 mV. Device-detected P-wave amplitudes decreased linearly during the 1 year before the first AHRE by 7.3% (CI, 5.1%-9.5%; P < .001 vs patients without AHRE).

Device-detected P-wave amplitudes <2.45 mV were associated with an increased risk of AHRE onset and progression to persistent forms of AHRE independent of the patient's risk profile.

Arrhythmias are increasingly recognized as severe complications of precapillary pulmonary hypertension, encompassing pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Despite their significant contribution to symptoms, morbidity, in-hospital mortality, and potentially sudden death in PAH/CTEPH, there remains a lack of comprehensive data on epidemiology, pathophysiology, and outcomes to inform the management of these patients. This review provides an overview of the latest evidence on this subject, spanning from the molecular mechanisms underlying arrhythmias in the hypertrophied or failing right heart to the clinical aspects of epidemiology, diagnosis, and treatment.

Atrial fibrillation (AF) causes progressive structural and electrical changes in the atria that can be summarized within the general concept of atrial remodeling. In parallel, other clinical characteristics and comorbidities may also affect atrial tissue properties and make the atria susceptible to AF initiation and its long-term persistence. Overall, pathological atrial changes lead to atrial cardiomyopathy with important implications for rhythm control. Although there is general agreement on the role of the atrial substrate for successful rhythm control in AF, the current classification oversimplifies clinical management. The classification uses temporal criteria and does not establish a well-defined strategy to characterize the individual-specific degree of atrial cardiomyopathy. Better characterization of atrial cardiomyopathy may improve the decision-making process on the most appropriate therapeutic option. We review current scientific evidence and propose a practical characterization of the atrial substrate based on 3 evaluation steps starting with a clinical evaluation (step 1), then assess outpatient complementary data (step 2), and finally include information from advanced diagnostic tools (step 3). The information from each of the steps or a combination thereof can be used to classify AF patients in 4 stages of atrial cardiomyopathy, which we also use to estimate the success on effective rhythm control.

Heart failure (HF) and atrial fibrillation (AF) are prevalent cardiovascular diseases that contribute significantly to morbidity, mortality, hospitalisation, and healthcare costs. It is not uncommon for these conditions to coexist and have mutually reinforcing effects. A critical factor in the aetiology of these conditions is oxidative stress, driven by reactive oxygen species (ROS), which contributes to atrial remodelling and fibrosis. The recent introduction of new drugs for the treatment of heart failure has also had an impact on the management of atrial fibrillation due to their influence on oxidative stress. The objective of this review is to analyse the effects of these therapies, including their role in mitigating ROS, on the prevention and treatment of AF in HF patients.

Reduced cardiorespiratory fitness (CRF) is an independent risk factor for the progression of atrial fibrillation (AF). We hypothesized that reduced CRF is associated with structural, functional, and electrical remodeling of the left atrium.

This study sought to correlate objectively assessed CRF with functional and electrical left atrial (LA) parameters using invasive and noninvasive assessments.

Consecutive patients with symptomatic AF undergoing catheter ablation were recruited. CRF was objectively quantified pre-ablation by using cardiopulmonary exercise testing. Using peak oxygen consumption, participants were classified as preserved CRF (>20 mL/kg/min) or reduced CRF (<20 mL/kg/min). LA stiffness was assessed invasively with hemodynamic monitoring and imaging during high-volume LA saline infusion. LA stiffness was calculated as ΔLA diameter/ΔLA pressure over the course of the infusion. LA function was assessed with echocardiographic measures of LA emptying fraction and LA strain. Electrical remodeling was assessed by using high-density electroanatomical maps for LA voltage and conduction.

In total, 100 participants were recruited; 43 had reduced CRF and 57 had preserved CRF. Patients with reduced CRF displayed elevated LA stiffness (P = 0.004), reduced LA emptying fraction (P = 0.006), and reduced LA reservoir strain (P < 0.001). Reduced CRF was also associated with reduced LA voltage (P = 0.039) with greater heterogeneity (P = 0.027) and conduction slowing (P = 0.04) with greater conduction heterogeneity (P = 0.02). On multivariable analysis, peak oxygen consumption was independently associated with LA stiffness (P = 0.003) and LA conduction velocities (P = 0.04).

Reduced CRF in patients with AF is independently associated with worse LA disease involving functional and electrical changes. Improving CRF may be a target for restoring LA function in AF.

Focal and rotational activations have been demonstrated in atrial fibrillation (AF), but their relationship to each other and to structural remodeling remains unclear.

The purpose of this study was to assess the relationship of focal and rotational activations to underlying low-voltage zones (LVZs) (<0.5 mV) and to determine whether there was a temporal (≤500 ms) and spatial (≤12 mm) relationship between these activations.

Patients undergoing catheter ablation for persistent AF were included. All patients underwent pulmonary vein isolation. Unipolar signals were collected to identify focal and rotational activations using a wavefront propagation algorithm.

In 40 patients, 105 activations were identified (57 [54.3%] focal; 48 [45.7%] rotational). Rotational activations were co-localized to LVZs (35/48 [72.9%]) whereas focal activations were not (11/57 in LVZ [19.3%]; P <.001). The proportion of the left atrium occupied by LVZs predicted rotational activations occurrence (area under the curve 0.96; 95% confidence interval 0.90-1.00; P <.001). In patients with a relatively healthy atrium, in which the atrium consisted of ≤15% LVZs, only focal activations were identified. Thirty-two of the 35 rotational activations (91.4%) located in LVZs also showed a temporal and spatial relationship to a focal activation. The presence of a LVZ within 12 mm of the focal activation was a strong predictor for whether a paired rotational activation would also occur in that vicinity.

Rotational activations are largely confined to areas of structural remodeling and have a clear spatial and temporal relationship with focal activations suggesting they are dependent on them. These novel mechanistic observations outline a plausible model for patient-specific mechanisms maintaining AF.

Lack of the typical nocturnal blood pressure (BP) fall, i.e non-dipper, has been known as a cardiovascular risk. However, the influence of non-dipper on atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been unclear. We investigated the clinical impact of non-dipping as evaluated by 24-hour ambulatory BP monitoring on the long-term outcome of AF recurrence post-PVI in 76 AF patients with a history of increased BP. The PVI procedure was successful in all 76 patients (mean age, 66±9years; antihypertensive medication, 89%; non-paroxysmal AF, 24%). Twenty patients had AF recurrence during a median follow-up of 1138 days. There was no difference in BP levels between the AF recurrence and non-recurrence groups (average 24 h systolic BP:126 ± 17 vs.125 ± 14 mmHg; P = 0.84). On the other hand, the patients with non-dipper had a higher AF recurrence than those with dipper (38.9% vs.15.0%; P = 0.018). In Cox hazard analysis adjusted by age, non-paroxysmal AF and average 24-hr systolic BP level, the non-dipper was an independent predictor of AF recurrence (HR 2.78 [95%CI:1.05-7.34], P = 0.039). Non-dipper patients had a larger left atrial (LA) volume index than the dipper patients (45.9 ± 17.3 vs.38.3 ± 10.2 ml/m2, P = 0.037). Among the 58 patients who underwent high-density voltage mapping in LA, 11 patients had a low-voltage area (LVA) defined as an area with a bipolar voltage < 0.5 mV. However, there was no association of LVA with non-dipper or dipper (22.2% vs.16.1%, P = 0.555). Non-dipper is an independent predictor of AF recurrence post-PVI. Management of abnormal diurnal BP variation post-PVI may be important.

Chronic kidney disease (CKD) is commonly associated with unfavorable cardiovascular outcomes and remains the leading cause of mortality in individuals with end-stage renal disease (ESRD). Despite substantial knowledge about the impact of CKD on the left heart, the right heart, which holds significant clinical relevance, has often been overlooked and inadequately assessed in ESRD patients who have undergone kidney transplant (KTx). This study aimed to evaluate the effects of KTx on the right heart chambers in ESRD patients. 57 adult KTx candidates were enrolled in this prospective longitudinal study, while 49 of them were included in the final assessment. Patients underwent a comprehensive cardiac assessment, including conventional echocardiography, speckle tracking echocardiography, and three-dimensional heart modeling both before and after surgery. Echocardiographic assessments showed significant increases in right ventricular (RV) ejection fraction, RV fractional area change (RVFAC), tricuspid annular plain systolic excursion, RV fractional shortening, right atrial (RA) reservoir, conduit, and booster strains, and RV global longitudinal strain (RVGLS). Moreover, significant reductions in RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume, RV end-diastolic diameter (RVEDD) in mid-cavity view, systolic pulmonary artery pressure was observed (all P values < 0.05). However, no significant difference was found in S velocity, as well as RVEDD in basal and apex-to-annulus view. Moreover, pre-KTx measurements of RVGLS, RVEDD (apex-to-annulus diameter), RV fractional shortening, and S velocity were predictors of RVGLS after KTx. RA conduit strain was also identified as a predictor of RA conduit strain after KTx. Additionally, age, RVEDV, RVESV, RVFAC, and RA reservoir strain before KTx were identified as independent predictors of RA reservoir strain after KTx. The findings of this study demonstrate a significant improvement in right heart function following KTx. Furthermore, strain analysis can provide valuable insights for predicting right heart function after KTx.

Device therapy is a nonpharmacological approach that presents a crucial advancement for managing patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). This review investigated the impact of device-based interventions and emphasized their potential for optimizing treatment for this complex patient demographic. Cardiac resynchronization therapy, augmented by atrioventricular node ablation with His-bundle pacing or left bundle-branch pacing, is effective for enhancing cardiac function and establishing atrioventricular synchrony. Cardiac contractility modulation and vagus nerve stimulation represent novel strategies for increasing myocardial contractility and adjusting the autonomic balance. Left ventricular expanders have demonstrated short-term benefits in HFpEF patients but require more investigation for long-term effectiveness and safety, especially in patients with AF. Research gaps regarding complications arising from left ventricular expander implantation need to be addressed. Device-based therapies for heart valve diseases, such as transcatheter aortic valve replacement and transcatheter edge-to-edge repair, show promise for patients with AF and HFpEF, particularly those with mitral or tricuspid regurgitation. Clinical evaluations show that these device therapies lessen AF occurrence, improve exercise tolerance, and boost left ventricular diastolic function. However, additional studies are required to perfect patient selection criteria and ascertain the long-term effectiveness and safety of these interventions. Our review underscores the significant potential of device therapy for improving the outcomes and quality of life for patients with AF and HFpEF.

Radiofrequency ablation (RFA) procedures for atrial fibrillation frequently fail to prevent recurrence, partially due to limitations in assessing extent of ablation. Optical spectroscopy shows promise in assessing RFA lesion formation but has not been validated in conditions resembling those in vivo.

Catheter-based near-infrared spectroscopy (NIRS) was applied to porcine hearts to demonstrate that spectrally derived optical indices remain accurate in blood and at oblique incidence angles.

Porcine left atria were ablated and mapped using a custom-fabricated NIRS catheter. Each atrium was mapped first in phosphate-buffered saline (PBS) then in porcine blood.

NIRS measurements showed little angle dependence up to 60 deg. A trained random forest model predicted lesions with a sensitivity of 81.7%, a specificity of 86.1%, and a receiver operating characteristic curve area of 0.921. Predicted lesion maps achieved a mean structural similarity index of 0.749 and a mean normalized inner product of 0.867 when comparing maps obtained in PBS and blood.

Catheter-based NIRS can precisely detect RFA lesions on left atria submerged in blood. Optical parameters are reliable in blood and without perpendicular contact, confirming their ability to provide useful feedback during in vivo RFA procedures.

Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19-0.84; P-value = 0.015). In contrast, among patients with an uplift score < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure.

Heart failure (HF) increases the probability of cardiac arrhythmias, including atrial fibrillation (AF), but the mechanisms linking HF to AF are poorly understood. We investigated disturbances in Ca2+ signaling and electrophysiology in rabbit atrial myocytes from normal and failing hearts and identified mechanisms that contribute to the higher risk of atrial arrhythmias in HF. Ca2+ transient (CaT) alternans-beat-to-beat alternations in CaT amplitude-served as indicator of increased arrhythmogenicity. We demonstrate that HF atrial myocytes were more prone to alternans despite no change in action potentials duration and only moderate decrease of L-type Ca2+ current. Ca2+/calmodulin-dependent kinase II (CaMKII) inhibition suppressed CaT alternans. Activation of IP3 signaling by endothelin-1 (ET-1) and angiotensin II (Ang II) resulted in acute, but transient reduction of CaT amplitude and sarcoplasmic reticulum (SR) Ca2+ load, and lowered the alternans risk. However, prolonged exposure to ET-1 and Ang II enhanced SR Ca2+ release and increased the degree of alternans. Inhibition of IP3 receptors prevented the transient ET-1 and Ang II effects and by itself increased the degree of CaT alternans. Our data suggest that activation of CaMKII and IP3 signaling contribute to atrial arrhythmogenesis in HF.

Calcific aortic valve stenosis (CAVS) is associated with an increased risk of atrial fibrillation (AF) in observational studies, but whether these associations are causal has not been determined. This study aimed to explore the potential causal relationship between CAVS and AF via Mendelian randomization (MR). Genetic variants from the genome-wide association study (GWAS) summary data of the European population for CAVS were used to investigate the association with AF. The inverse variance weighted (IVW) approach was used to obtain the primary causal inference, and several sensitivity analysis approaches, such as the MR‒Egger and weighted median (WM), were performed to assess the robustness of the results. A total of nineteen valid and independent genetic SNPs associated with CAVS were obtained from the GWAS database. Genetically predicted CAVS (OR: 1.105; 95% CI: 1.072-1.139; p = 8.60E-11) was associated with an increased risk of AF. Similar results were discovered in the sensitivity analyses by using MR Egger and weighted median approaches. An MR design was used to reduce confounding variables and the potential for reverse causality bias. The results provide genetic evidence that CAVS considerably increased the risk of AF.

The left atrium (LA) plays a critical role in receiving pulmonary venous return and modulating left ventricular (LV) filling. With the onset of exercise, LA function contributes to the augmentation in stroke volume. Due to the growing focus on atrial imaging, there is now evidence that structural remodeling and dysfunction of the LA is associated with adverse outcomes including incident cardiovascular disease. In patients with established disease, pathological changes in atrial structure and function are associated with exercise intolerance, increased hospital admissions and mortality, independent of left ventricular function. Exercise training is widely recommended in patients with cardiovascular disease to improve patient outcomes and maintain functional capacity. There are widely documented changes in LV function with exercise, yet less attention has been given to the LA. In this review, we first describe LA physiology at rest and during exercise, before exploring its association with cardiac disease outcomes including atrial fibrillation, heart failure, and stroke. The adaptation of the LA to short- and longer-term exercise training is evaluated through review of longitudinal studies of exercise training in healthy participants free of cardiovascular disease and athletes. We then consider the changes in LA structure and function among patients with established disease, where adverse atrial remodeling may be implicated in the disease process. Finally, we consider important future directions for assessment of atrial structure and function using novel imaging modalities, in response to acute and chronic exercise.

Ultra-high-density mapping systems allow more precise measurement of the heart chambers at corresponding conduction velocities (CVs) and voltage amplitudes (VAs). Our aim for this study was to define and compare a basic value set for unipolar CV and VA in all four heart chambers and their separate walls in healthy, juvenile porcine hearts using ultra-high-density mapping.

We used the Rhythmia Mapping System to create electroanatomical maps of four pig hearts in sinus rhythm. CVs and VAs were calculated for chambers and wall segments with overlapping circular areas (radius of 5 mm).

We analysed 21 maps with a resolution of 1.4 points/mm2. CVs were highest in the left atrium (LA), followed by the left ventricle (LV), right ventricle (RV), and right atrium (RA). As for VA, LV was highest, followed by RV, LA, and RA. The left chambers had a higher overall CV and VA than the right. Within the chambers, CV varied more in the right than in the left chambers, and VA varied in the ventricles but not in the atria. There was a slightly positive correlation between CVs and VAs at velocity values of <1.5 m/s.

In healthy porcine hearts, the left chambers showed higher VAs and CVs than the right. CV differs mainly within the right chambers and VA differs only within the ventricles. A slightly positive linear correlation was found between slow CVs and low VAs.

Atrial fibrillation is the most common type of cardiac arrhythmias in humans, mostly caused by hyper excitation of specific areas in the atrium resulting in dyssynchronous atrial contractions, leading to severe consequences such as heart failure and stroke. Current therapeutics aim to target this condition through both pharmacological and non-pharmacological approaches. To test and validate any of these treatments, an appropriate preclinical model must be carefully chosen to refine and optimise the therapy features to correctly reverse this condition. A broad range of preclinical models have been developed over the years, with specific features and advantages to closely mimic the pathophysiology of atrial fibrillation. In this review, currently available models are described, from traditional animal models and in vitro cell cultures to state-of-the-art organoids and organs-on-a-chip. The advantages, applications and limitations of each model are discussed, providing the information to select the appropriate model for each research application.

Optimal method for voltage assessment in AF remains unclear.

This study evaluated different methods for assessing atrial voltage and their accuracy in identifying pulmonary vein reconnection sites (PVRSs) in atrial fibrillation (AF).

Patients with persistent AF undergoing ablation were included. De novo procedures: voltage assessment in AF with omnipolar voltage (OV) and bipolar voltage (BV) methodology and BV assessment in sinus rhythm (SR). Activation vector and fractionation maps were reviewed at voltage discrepancy sites on OV and BV maps in AF. AF voltage maps were compared with SR BV maps. Repeat ablation procedures: OV and BV maps in AF were compared to detect gaps in wide area circumferential ablation (WACA) lines that correlated with PVRS.

Forty patients were included: 20 de novo and 20 repeat procedures. De novo procedure: OV vs BV maps in AF; average voltage 0.55 ± 0.18 mV vs 0.38 ± 0.12 mV; P = 0.002, voltage difference of 0.20 ± 0.07 mV; P = 0.003 at coregistered points and proportion of left atrium (LA) area occupied by low-voltage zones (LVZs) was smaller on OV maps (42.4% ± 12.8% OV vs 66.7% ± 12.7% BV; P < 0.001). LVZs identified on BV maps and not on OV maps correlated frequently to wavefront collision and fractionation sites (94.7%). OV AF maps agreed better with BV SR maps (voltage difference at coregistered points 0.09 ± 0.03 mV; P = 0.24) unlike BV AF maps (0.17 ± 0.07 mV, P = 0.002). Repeat ablation procedure: OV was superior in identifying WACA line gaps that correlated with PVRS than BV maps (area under the curve = 0.89, P < 0.001).

OV AF maps improve voltage assessment by overcoming the impact of wavefront collision and fractionation. OV AF maps correlate better with BV maps in SR and more accurately delineate gaps on WACA lines at PVRS.

The development of atrial flutter and fibrillation (AFL/AF) in patients with pre-capillary pulmonary hypertension has been associated with an increased risk of morbidity and mortality. Rate and rhythm control strategies have not been directly compared.

Eighty-four patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) with new-onset AFL/AF were identified in the ASPIRE registry. First, baseline characteristics and rates of sinus rhythm (SR) restoration of 3 arrhythmia management strategies (rate control, medical rhythm control and DC cardioversion, DCCV) in an early (2009-13) and later (2014-19) cohort were compared. Longer-term outcomes in patients who achieved SR versus those who did not were then explored.

Sixty (71%) patients had AFL and 24 (29%) AF. Eighteen (22%) patients underwent rate control, 22 (26%) medical rhythm control and 44 (52%) DCCV. SR was restored in 33% treated by rate control, 59% medical rhythm control and 95% DCCV (p < 0.001). Restoration of SR was associated with greater improvement in functional class (FC) and Incremental Shuttle Walk Distance (p both <0.05). It also independently predicted superior survival (3-year survival 62% vs 23% in those remaining in AFL/AF, p < 0.0001). In addition, FC III/IV independently predicted higher mortality (HR 2.86, p = 0.007). Right atrial area independently predicted AFL/AF recurrence (OR 1.08, p = 0.01). DCCV was generally well tolerated with no immediate major complications.

Restoration of SR is associated with superior functional improvement and survival in PAH/CTEPH compared with rate control. DCCV is generally safe and is more effective than medical therapy at achieving SR.

Radiofrequency (RF) linear ablation at the left atrial (LA) roof and bottom to isolate the LA posterior wall using contiguous and optimized RF lesions was evaluated. Achieving isolation of the LA posterior wall is challenging as two continuous linear lesion sets are necessary.

Forty consecutive patients with symptomatic atrial fibrillation (AF) and arrhythmia substrates affecting the LA posterior wall underwent posterior wall isolation by linear lesions across the roof and bottom. The cohort was divided into two groups: group 1 (20 patients) linear ablation guided by contact force (CF) only; group 2 (20 patients) guided by ablation index (AI) and interlesion distance.

Bidirectional block across the LA roof and bottom was achieved in 40/40 patients. Additional endocardial RF applications in 5 patients from group 1 vs. 3 patients from group 2 resulted in posterior wall isolation in all patients. Procedure duration was almost equal in both groups. CF and AI were significantly higher in group 2 for the roof line, whereas no statistical difference was found for the bottom line. AI-guided LA posterior wall isolation led to a significantly lower maximum temperature increase. The mean AI value as well as the mean value for catheter-to-tissue CF for the roof line were significantly higher when AI-guided ablation was performed. Standard deviation in group 2 showed a remarkably lower dispersion.

Ablation index guided posterior wall isolation for substrate modification is safe and effective. AI guided application of the posterior box lesion allows improved lesion formation.

Cardiac amyloidosis (CA), caused by the deposition of insoluble amyloid fibrils, impairs different cardiac structures, altering not only left ventricle (LV) systo-diastolic function but also atrial function and the conduction system. The consequences of the involvement of the cardiac electrical system deserve more attention, as well as the study of the underlying molecular mechanisms. This is an issue of considerable interest, given the conflicting data on the effectiveness of conventional antiarrhythmic strategies. Therefore, this review aims at summarizing the arrhythmic burden related to CA and the available evidence on antiarrhythmic treatment in this population.