Subjects In Sinus Rhythm Research Articles

Tricuspid annular and right atrial volume changes are associated in healthy adults-insights from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

The tricuspid valve and its annulus (TA) and the right atrium (RA) play a significant role in regulating blood flow in the right heart. However, their effect on each other is not fully understood even in normal circumstances. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) is able to simultaneously assess TA and RA at the same time in a non-invasive way. The present study aimed to examine associations between tricuspid annular (TA) dimensions and right atrial (RA) volumes in healthy adults by 3DSTE. The present study comprised 144 healthy subjects (mean age: 34.4 ± 12.6 years, 72 males), who participated in this study on a voluntary basis for screening between 2011 and 2015. In all subjects, electrocardiography, two-dimensional Doppler echocardiography and 3DSTE have been performed. With increasing end-systolic maximum RA volume, all end-systolic and end-diastolic TA dimensions showed simultaneous increase, but in various degrees resulting in (non-significant) reduction of TA functional properties. Similarly, with increasing diastolic pre-atrial contraction and minimum RA volumes, TA dimensions increased simultaneously (except end-diastolic TA diameter), but in various degrees resulting in reduced TA fractional shortening and fractional area change. With increasing RA dimensions, end-systolic and end-diastolic TA dimensions showed simultaneous increase, but in different, sometimes not significant degrees. While RA stroke volumes showed increasing pattern with TA dilation, RA emptying fractions have not changed substantially. 3DSTE is suitable for non-invasive assessment of TA dimensions and RA volumes at the same time using the same 3D echocardiographic dataset. Significant associations between TA size and RA volumes exist in healthy circumstances. Strong associations in case of dilation of TA in the presence of higher RA volumes could partly explain functional tricuspid regurgitation later developing in subjects in sinus rhythm.

A unified framework for multi-lead ECG characterization using Laplacian Eigenmaps

Background. The analysis of multi-lead electrocardiographic (ECG) signals requires integrating the information derived from each lead to reach clinically relevant conclusions. This analysis could benefit from data-driven methods compacting the information in those leads into lower-dimensional representations (i.e. 2 or 3 dimensions instead of 12). Objective. We propose Laplacian Eigenmaps (LE) to create a unified framework where ECGs from different subjects can be compared and their abnormalities are enhanced. Approach. We conceive a normal reference ECG space based on LE, calculated using signals of healthy subjects in sinus rhythm. Signals from new subjects can be mapped onto this reference space creating a loop per heartbeat that captures ECG abnormalities. A set of parameters, based on distance metrics and on the shape of loops, are proposed to quantify the differences between subjects. Main results. This methodology was applied to find structural and arrhythmogenic changes in the ECG. The LE framework consistently captured the characteristics of healthy ECGs, confirming that normal signals behaved similarly in the LE space. Significant differences between normal signals, and those from patients with ischemic heart disease or dilated cardiomyopathy were detected. In contrast, LE biomarkers did not identify differences between patients with cardiomyopathy and a history of ventricular arrhythmia and their matched controls. Significance. This LE unified framework offers a new representation of multi-lead signals, reducing dimensionality while enhancing imperceptible abnormalities and enabling the comparison of signals of different subjects.

Atrial fibrillation is an independent risk factor for heart failure progression and pump failure mortality in HFpEF:: a propensity score matched analysis of the TOPCAT Americas study

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is associated with excess mortality and cardiovascular (CV) hospitalizations in HF patients (pts) with preserved systolic function (pEF) but the contributing factors to these outcomes are not known.. Purpose To analyze the independent impact of AF on clinical outcomes of HFpEF pts in the TOPCAT AMERICAS study using propensity score matched (PSM) cohorts to account for confounding by other comorbidities. Methods Study cohorts were PSM matched for 20 clinical, demographic & ECG variables. 3 matched cohorts based on baseline rhythm status at study entry were compared viz. subjects in sinus rhythm (SR), subjects in AF on baseline ECG & subjects with Any AF event by history or ECG. We analyzed CV mortality, adjudicated modes of death & morbidity during a mean follow up period of 2.9 yrs. Results 418 subjects in SR (SR cohort) were PSM with 418 subjects in AF on baseline ECG (AF on ECG cohort) & 418 pts with any AF event by history or ECG (Any AF cohort) at study entry. Any AF increased the risk of CV death (D), pump failure death (PFD), CV and HF hospitalization (H) and HF progression. AF on ECG increased risk of CVD, CVH, HFH and PFD (Tables). Neither AF cohort increased risk of sudden death (SD) {Figure}. Conclusion 1. AF is an independent risk factor for worsening CV outcomes in HFpEF. 2. This increased risk is due to a selective increase in symptomatic HF progression from early to advanced HF, HFH and PFD in advanced HF rather than SD. 3. Loss of AV synchrony & rate control in AF can independently impact HF progression in HFpEF with consequent HFH and PFD. Restoration of SR may offer benefits for CV outcomes in HFpEF & warrants evaluation.

The novel left atrial appendage strain parameters are associated with thrombosis risk in patients with non-valvular atrial fibrillation.

We sought to explore a novel left atrial appendage (LAA) strain parameter which could represent the cumulative adverse impact of chronic Atrial fibrillation (AF) on the LAA function, and the relationship between the LAA strain parameter and thrombosis risk in patients with non-valvular AF. We enrolled 268 patients with non-valvular AF and 58 sinus rhythm subjects who underwent transesophageal echocardiography in the study. LAA longitudinal strain amplitude (LAA LSA) was defined as the sum of the value of the maximum positive peak strain (LAA PLS) and the absolute value of the minimum negative peak strain (LAA NLS). Dense spontaneous echo contrast (SEC) was defined as grade 3 or 4 SEC. Compared to sinus rhythm group, the global LAA strain parameters were significantly lower in paroxysmal AF (n = 148), and the lowest of them were found in persistent AF (n = 120), which suggested that the global LAA strain parameters could evaluate LAA function in sinus rhythm, paroxysmal AF and persistent AF. Compared with patients in AF without SEC/thrombus (n = 113), the regional and global LAA strain parameters were significantly depressed in AF with SEC/thrombus (n = 155). Multivariate logistic regression analyses showed that LAA global LSA (OR 0.768; 95% CI:0.569, 0.970; p = 0.027) was an independent predicter of the SEC/thrombus. Compared with patients in AF without dense SEC or thrombus (n = 210), the regional and global LAA strain parameters were significantly impaired in the patients with dense SEC/thrombus(n = 58). LAA global LSA (AUC 0.884) had the best predictable accuracy for dense SEC or thrombus, and outperformed LAA PLS, LAA NLS, CHA2DS2-VASc score and conventional LAA functional parameters that have been used in the evaluation blood flow stasis in LAA. LAA LSA showed excellent interobserver and intra-observer agreement beyond LAA PLS and LAA NLS. The novel LAA strain parameters, which were feasible and reproducible parameters for evaluation LAA mechanic function, had good predictive accuracy for blood flow stasis in LAA beyond conventional LAA functional parameters.

Atrial Fibrillation can adversely impact Heart Failure with Preserved Ejection Fraction by its association with Heart Failure Progression and Mortality: A Post-Hoc Propensity Score-Matched Analysis of the TOPCAT Americas Trial.

Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity. We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11-1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12-1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05-3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04-1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02-2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11-4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09-1.72, P = 0.006 and HR 1.65, 95% CI 1.22-2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF. Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF. TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302.

S-29-5: EARLY CHANGES IN LEFT ATRIAL STRAIN AND GLOBAL VENTRICULAR FUNCTION IN HYPERTENSIVE PATIENTS WITH HEART FAILURE WITH PRESERVED EF

Background: Hypertension is one of leading causes in heart failure with preserved ejection fraction (HFpEF).Left atrial (LA) maximal volume and index (LAVI) had a prognostic value in patients with heart failure and incidence of atrial fibrilation (AF). Recently, LA mechanical function and LA strain have been introduced as alternative methods to assess LA performance more accuratly. Aim: To evaluate the relation between early changes in LA function and strain (PALS) and correlate the association with global left ventricular (LV) function and longitudinal strain (GLS) in patients with HFpEF.and arterial hypertension. Methods: We evaluated 152 subjects in sinus rhythm: 22 normals (31y ± 5), and 70 pts with HFpEF (65y ± 12), 60 pts HFrEF (64 y ± 10). Echocardiography was performed in all patients and follow up after 12 monts and analyzed offline in order to extract the global and segmental strain values of the LV and LA and LA volume and LAVI. Results: The two groups of patients were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. The LA diameter and maximal volume were higher in HFrEF group. The GLS is significantly reduced in HFrEF group. LV GLS is the main parameter for myocardial dysfunction, which changed significantly in the HFrEF (p < 0,001) at 12mFU. Reduced PALS in HFrEF was associated with impairment of all measures of LV systolic and diastolic function and events of atrial fibrilation / 33 % in HFrEF and 12 % in HFpEF/ and the correlation between global longitudinal strain and PALS was highly significant (p < 0.001; r = 0.71). At 12mFU, PALS was significantly associated with lower global longitudinal strain in group with HFrEF (p < 0.001, r = 0.61), LAVI > 28 ml/m2 (p < 0.01,r = 0.57) and slightly decreased in HFpEF /p < 0.5, r = 0.34/. ROC analysis shows the cut of value of 29 % for PALS which correlated with AF events. Conclusions: PALS and GLS are significantly reduced in HFpEF patients and decreased in HFpEF. PALS provides additional,prognostic value beyond LA volume and LAVI. Severe LV myocardial dysfunction and reduced GLS and decreased PALS, even still normal LAVI is a prognostic index for AF.

Abstract 12553: Adverse Cardiovascular Outcomes in Heart Failure (HF) With Preserved Systolic Function Associated With Atrial Fibrillation Are Due to Loss of Rhythm Control Impacting HF Status : A Propensity Score Matched Analysis of the TOPCAT Americas Study

Background: Atrial fibrillation (AF) is associated with excess mortality and cardiovascular (CV) hospitalizations in HF patients (pts) with preserved systolic function (pEF), Whether this is due to advanced co-morbidities or loss of atrioventricular (AV) synchrony & rate control in AF is unclear. Hypothesis: To analyze the independent impact of AF on clinical outcomes of HFpEF pts in the TOPCAT AMERICAS study using propensity score matched (PSM) cohorts to account for confounding by other comorbidities. Methods: Study cohorts were matched for 20 clinical, demographic & ECG variables. 3 matched cohorts based on baseline rhythm status at study entry were compared viz. subjects in sinus rhythm (SR), subjects in AF on baseline ECG & subjects with Any AF event by history or ECG. We analyzed CV mortality, adjudicated modes of death & morbidity during a mean follow up period of 2.9 yrs. Results: 418 subjects in SR (SR cohort) were PSM with 418 subjects in AF on baseline ECG (AF on ECG cohort) & 418 pts with any AF event by history or ECG (Any AF cohort) at study entry. Any AF increased risk of CV death(D), pump failure death (PFD), CV and HF hospitalization(H) and HF progression. AF on ECG increased risk of CVD, CVH, HFH and PFD (Tables). Neither AF cohort increased risk of sudden death (SD) {Figure}. Conclusion: 1. AF is an independent risk factor for worsening CV outcomes in HFpEF. 2. This increased risk is due to a selective increase in HF worsening, HFH and PFD rather than SD. 3. Loss of AV synchrony & rate control in AF can independently impact HF progression in HFpEF with consequent HFH and PFD. Restoration of SR may offer benefits for CV outcomes in HFpEF & warrants evaluation.

Correlation Between Serum Albumin and D-Dimer Levels in 909 Patients with Non-Valvular Atrial Fibrillation: A Retrospective Study from a Single Center in China.

BACKGROUND D-dimer level can reflect the hypercoagulable state of atrial fibrillation (AF) and predict thromboembolic events. However, no effective indicator associated with D-dimer of AF patients has been found to prevent thromboembolic events in AF. This retrospective study from a single center aimed to investigate the correlation between serum albumin and D-dimer levels in 909 patients with non-valvular AF (NVAF) and 653 subjects in sinus rhythm. MATERIAL AND METHODS A total of 909 NVAF patients and 653 sex- and age-matched sinus rhythm participants were used to compare serum albumin and D-dimer levels. Serum albumin was determined by colorimetry, and D-dimer level was determined by latex-enhanced photoimmunoassay. We analyzed the correlation of serum albumin and D-dimer with NVAF by correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve. RESULTS Albumin (P<0.001) and D-dimer (P<0.001) were significantly associated with NVAF. Among NVAF patients, D-dimer level was negatively correlated with albumin levels (P<0.001), and albumin level was an independent risk factor of abnormal D-dimer level (>0.5 ug/mL), which was also an effective predictor of abnormal D-dimer level (the area under the ROC curve was 0.77, P<0.001), and the optimal cutoff value was 36.95 g/L. CONCLUSIONS Serum albumin and D-dimer levels were significantly associated with NVAF. In NVAF patients, D-dimer level was inversely correlated with albumin levels, and albumin level was an independent risk factor and effective predictor of abnormal D-dimer level. Close examination and supplementation of serum albumin can prevent thromboembolic events, but further clinical research and confirmation are needed.

Low voltage area as a predictor of recurrence after a single pulmonary vein isolation procedure: results of the WAVE-MAP AF study

Abstract Background/Introduction Pulmonary vein isolation (PVI) is a recommended approach for atrial fibrillation (AF) ablation procedures. Substrate modification beyond PVI has mixed results but identifying and ablating low voltage zones and ablating those targets in addition to PVI may be beneficial. Electroanatomic mapping is critical to identify subjects that may require further substrate modification. Low voltage area may be predictive of optimal treatment approach. Purpose This was a prospective, multicenter, interventional study of a high-density grid-style mapping catheter (HD Grid) to characterize left atrial low voltage substrate during sinus rhythm (SR) and AF and identify associations with 12 month recurrence rates after a single de novo radiofrequency (RF) ablation using a PVI only approach. Methods This study (NCT03882021) enrolled 300 subjects at 18 centers in Europe and Israel. Subjects underwent de novo RF ablation for paroxysmal AF (PAF) (N=113), early persistent AF (PsAF; AF sustained 7 days to 3 months) (N=86) or non-early PsAF (AF sustained &amp;gt;3 months to 12 months) (N=101). High density voltage maps were collected with HD Grid. Two pre-ablation maps, in SR and AF, were created for each subject (N=196) followed by PVI only ablation. Low voltage area (using cutoffs of 0.1 mV to 1.5 mV) was investigated in SR and AF. Follow up visits were at 3, 6 and 12 months post-ablation, with a 24-hour Holter monitor at 12 months. A Cox proportional hazards model was used to identify associations between mapping data and 12 month AF/atrial flutter (AFL)/atrial tachycardia (AT) recurrence after a single PVI procedure. Results At 12 months, 75.5% of subjects were free from AF/AFL/AT recurrence. On average, PsAF subjects had more low voltage area than PAF subjects in SR and AF. However, while univariate analysis found no correlation between recurrence and PAF or PsAF diagnosis (p=0.1261), those with recurrence had a significantly larger percent left atrial low voltage area under 0.5 mV with simultaneous orthogonal bipole wave configuration (HDW) in both AF (p=0.0011) and SR (p=0.0210) than those without recurrence. Using HDW, low voltage area (identified as &amp;lt;0.5 mV) greater than 28% of the left atrium in SR (HR: 4.82, 95% CI: 2.08–11.18, p=0.0003) and greater than 72% in AF (HR: 5.66, 95% CI: 2.34–13.69, p=0.0001) were associated with a higher risk of AF/AFL/AT recurrence at one year. Conclusion(s) Using a standard cutoff of 0.5 mV, a larger percent low voltage area was associated with increased risk of recurrence in both SR and AF. Future analyses will explore optimal low voltage cutoffs and thresholds predictive of recurrence that may necessitate additional substrate modification beyond PVI. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Left atrial vorticity is independently associated with embolic brain infarcts and represents a promising imaging biomarker of cardioembolism in sinus rhythm and atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with embolic stroke, but risk scores such as CHA2DS2-VASc perform only modestly (C statistics 0.6–0.7). Meanwhile, up to 25% of embolic strokes in patients without AF have no identifiable cause, and occult left atrial (LA) thromboembolism may be a relevant mechanism in such cases. Purpose We hypothesised that imaging of left atrial blood flow could improve embolic risk prediction in patients with and without AF. We used 4D flow magnetic resonance imaging (MRI) to identify a biomarker that is: (a) independently associated with embolic brain infarction by brain MRI, (b) able to stratify blood flow characteristics both during AF and in sinus rhythm (SR), and (c) reproducible. Methods We recruited 3 patient cohorts to respectively address each aim. Firstly, to assess the association between LA flow parameters and embolic brain infarcts, we recruited cohort A, consisting of 134 patients (41% female; age 70±9 years) with a history of ischaemic stroke (N=44) or no history of stroke but with CHA2DS2VASc score ≥1 (N=90). Next, the sensitivity of 4D flow parameters to rhythm change was assessed in cohort B: 37 patients with persistent AF studied before and after cardioversion, whose results were compared with those of 23 healthy controls in SR [CHA2DS2-VASc = 0.0 (0.0–0.0)]. Finally, scan-rescan coefficients of variation (CV) and interval-scan CV at 30 days were determined in Cohort C (86 subjects; 64 in SR, 22 in AF). Brain MRI was used to identify large non-cortical or cortical brain infarcts (LNCCI) – i.e. infarcts likely to be embolic in origin. Results At least one LNCCI was present in 39 of 134 patients in cohort A. Lower LA vorticity was significantly associated with higher risk of prevalent LNCCIs (Figure 1), after adjustment for AF, age, and CHA2DS2VASc score [OR=2.10 (95% CI 1.12–3.92) per SD, P=0.02]. This association remained significant after further adjustment for other cardiac parameters (all P&amp;lt;0.05, Figure 1). By contrast, there was no significant association between peak velocity and LNCCIs (P=0.21). LA vorticity was sensitive to rhythm change, improving significantly in patients in cohort B in SR at ≥4 weeks after cardioversion (CV) of persistent AF (Figure 2A, paired P&amp;lt;0.001 vs pre-CV), but remained impaired compared to healthy controls (Figure 2B, P&amp;lt;0.01). Finally, reproducibility studies in cohort C showed that LA vorticity had a same-day scan-rescan CV of 7% without significant differences between SR and AF subjects (P&amp;gt;0.05), and also showed no significant temporal variability on interval scanning (P&amp;gt;0.05). Conclusions LA vorticity is reproducible, sensitive to changes in heart rhythm, and independently associated with embolic brain infarcts, suggesting a promising imaging biomarker of cardioembolism in SR and AF. LA blood flow imaging could improve stroke prediction and the personalisation of decisions about anticoagulation, regardless of heart rhythm. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Oxford BRC, BHF

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

BackgroundThe immune system significantly participates in the pathologic process of atrial fibrillation (AF). However, the molecular mechanisms underlying this participation are not completely explained. The current research aimed to identify critical genes and immune cells that participate in the pathologic process of AF.MethodsCIBERSORT was utilized to reveal the immune cell infiltration pattern in AF patients. Meanwhile, weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules that were significantly correlated with AF. The characteristic genes correlated with AF were identified by the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithm.ResultsIn comparison to sinus rhythm (SR) individuals, we observed that fewer activated mast cells and regulatory T cells (Tregs), as well as more gamma delta T cells, resting mast cells, and M2 macrophages, were infiltrated in AF patients. Three significant modules (pink, red, and magenta) were identified to be significantly associated with AF. Gene enrichment analysis showed that all 717 genes were associated with immunity- or inflammation-related pathways and biological processes. Four hub genes (GALNT16, HTR2B, BEX2, and RAB8A) were revealed to be significantly correlated with AF by the SVM-RFE algorithm and LASSO logistic regression. qRT–PCR results suggested that compared to the SR subjects, AF patients exhibited significantly reduced BEX2 and GALNT16 expression, as well as dramatically elevated HTR2B expression. The AUC measurement showed that the diagnostic efficiency of BEX2, HTR2B, and GALNT16 in the training set was 0.836, 0.883, and 0.893, respectively, and 0.858, 0.861, and 0.915, respectively, in the validation set.ConclusionsThree novel genes, BEX2, HTR2B, and GALNT16, were identified by WGCNA combined with machine learning, which provides potential new therapeutic targets for the early diagnosis and prevention of AF.

High density wave mapping to characterize low voltage substrate in sinus rhythm and atrial fibrillation: acute results from the WAVE-MAP AF study

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Background Pulmonary vein isolation (PVI) is a recommended approach for all atrial fibrillation (AF) ablation procedures, but PVI alone does not cure all AF. Supplementary substrate modification beyond PVI has mixed results. Identifying low voltage zones and ablating those targets in addition to PVI may be beneficial. Electroanatomic mapping is critical to identify subjects that may require further substrate modification. The amount of low voltage area may be predictive of the optimal treatment approach. Purpose This was a prospective, multicenter, interventional study of a high-density grid-style mapping catheter (HD Grid) to characterize left atrial (LA) low voltage substrate during sinus rhythm (SR) and AF in subjects undergoing de novo radiofrequency (RF) ablation for paroxysmal AF (PAF), early persistent AF (PsAF) (7 days-3 months) or non-early PsAF (&amp;gt;3 months-12 months) using a PVI only approach. Methods High-density voltage maps were collected with HD Grid during both SR and AF prior to ablation. Differences in low voltage area between (1) SR and AF and (2) simultaneous orthogonal bipole wave configuration (HDW) and standard along-the-spline linear electrode configuration (SD) were investigated. Results Three hundred subjects, enrolled at 18 centers in Europe and Israel, underwent PVI only RF ablation for PAF (N=113), early PsAF (N=79), and non-early PsAF (N=108). The average age was 62.0 ± 9.5 years and 70.3% (211/300) were male. SR maps and AF maps were available and evaluated in HDW and SD for 196 subjects (65.3%) (63 PAF, 65 early PsAF, 68 non-early PsAF). Mean LA surface area was 108.8 cm² and mean mapped surface area ranged from 83.2 to 89.5 cm². HDW maps showed less low voltage area compared to SD in all subgroups, both in AF and in SR (Figure). For example, in AF with a low voltage cutoff of 0.5 mV, mean low voltage area was 49.8 cm² using SD and only 45.6 cm² using HDW (p&amp;lt;.0001). Similarly, in SR with a low voltage cutoff of 0.5 mV, mean low voltage area was 16.1 cm² using SD and only 12.6 cm² using HDW (p&amp;lt;.0001). HDW showed significantly less low voltage area than SD in SR for all measured voltage cutoffs from 0.1 mV to 1.5 mV. On average, non-early PsAF subjects had a larger low voltage area than early PsAF subjects and PAF subjects in both SR and AF. In SR HDW, non-early PsAF subjects had 15.6 cm² under 0.5 mV, early PsAF subjects had 12.4 cm², and PAF subjects had 9.2 cm² (p=.0316). In AF HDW, non-early PsAF subjects had 56.6 cm² under 0.5 mV, early PsAF had 42.8 cm² and PAF subjects had 35.4 cm² (p&amp;lt;.0001). Conclusion Non-early PsAF subjects had the largest low voltage area on average compared to both early PsAF and PAF subjects in this study. Using HD grid, HDW provided better low voltage area characterization compared to SD in both SR and AF. The final results of this study will suggest whether an HDW substrate characterization of low voltage area can predict recurrences after a single PVI-only strategy procedure.

Association between early changes in left atrial strain and global left ventricular function in patients with heart failure with preserved EF ( HFpEF)

Abstract Funding Acknowledgements Type of funding sources: None. Background Left atrial (LA) maximal volume and index (LAVI) had a prognostic value in patients with heart failure and incidence of atrial fibrilation(AF) . Recently, LA mechanical function and LA strain have been introduced as alternative methods to assess LA performance more accuratly. Aim To evaluate the relation between early changes in LA function and strain ( PALS) and correlate the association with global left ventricular (LV) function and longitudinal strain (GLS) in patients with HFpEF. Methods We evaluated 132 subjects in sinus rhythm: 22 normals (31y ± 5), and 70 pts with HFpEF (65y ± 12), 60 pts HFrEF ( 64 y ± 10). Echocardiography was performed in all patients and follow up after 12 monts and analyzed offline in order to extract the global and segmental strain values of the LV and LA and LA volume and LAVI. Results The two groups of patients were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. The LA diameter and maximal volume were higher in HFrEF group. The GLS is significantly reduced in HFrEF group. LV GLS is the main parameter for myocardial dysfunction, which changed significantly in the HFrEF (p &amp;lt; 0,001) at 12mFU. Reduced PALS in HFrEF was associated with impairment of all measures of LV systolic and diastolic function and events of atrial fibrilation / 33 % in HFrEF and 12 % in HFpEF/ and the correlation between global longitudinal strain and PALS was highly significant (p &amp;lt; 0.001; r=-0.71). At 12mFU, PALS was significantly associated with lower global longitudinal strain in group with HFrEF (p &amp;lt; 0.001, r = 0.61 ), LAVI &amp;gt; 28 ml/m2 (p &amp;lt; 0.01,r = 0.57) and slightly decreased in HFpEF /p &amp;lt;0.5, r =0.34/. ROC analysis shows the cut –of value of 29 % for PALS which correlated with AF events. Conclusions: PALS and GLS are significantly reduced in HFpEF patients and decreased in HFpEF. PALS provides additional ,prognostic value beyond LA volume and LAVI. Severe LV myocardial dysfunction and reduced GLS and decreased PALS, even still normal LAVI is a prognostic index for AF.

Imaging of arrhythmia: Real-time cardiac magnetic resonance imaging in atrial fibrillation

ObjectivesQuantitative evaluations of function, volume and mass are fundamental in the diagnostic workup of different cardiovascular diseases and can be exactly determined by CMRI in sinus rhythm. This does not hold true in arrhythmia as CMR is hampered by reconstruction artifacts caused by inconsistent data from multiple heartbeats. Real-time (RT) MRI at high temporal resolution might reduce these problems. MethodsConsecutive patients with atrial fibrillation were prospectively included and underwent RT and conventional CINE CMR in randomized order. 29 patients were studied at 1.5 T and 30 patients at 3 T. At 3 T a group of 20 subjects in sinus rhythm served as controls. RT and CINE image quality was evaluated in different planes and for different wall sections using a Likert scale (from zero to four). Volumetric analysis was performed using two types of software and differences between RT and CINE CMR were evaluated. ResultsIn patients with atrial fibrillation RT CMR short axis (SA) resulted in a significantly higher image quality compared to CINE imaging both at 1.5 T and 3 T (1.5 T: mid SA: 3.55 ± 0.5 RT vs 2.6 ± 0.9 CINE, p = 0.0001; 3 T: mid SA: 3.15 ± 0.9 RT vs 2.6 ±1.0 CINE, p = 0.03); This qualitative difference was more marked and significant for the long axis views (2CV and 4CV) at 1.5 T (1.5 T: 2CV: 3.2 ± 0.6 RT vs 2.65 ± 1.1 CINE; p = 0.011; 4CV: 2.9 ± 0.69 RT vs 2.4 ± 0.9 CINE; p = 0.0044). During sinus rhythm CINE images were superior concerning diagnostic quality (3 T mid SA: 3.35 ± 0.45 RT vs 3.8 ± 0.5 CINE, p = 0.008). Quantitative analysis was successful with both software packages and the results showed a good correlation (Pearson correlation between 0.679 and 0.921 for patients). RT CMR resulted in slightly lower functional volumes than CINE CMR (3 T: patients: EDVI 86 ± 29 ml/m2 RT vs 93 29 ml/m2± 29 CINE, Pearson r = 0.902) but similar ejection fractions (3 T: patients: EF 47 ± 16% RT vs 45 ± 13% CINE, Pearson r = 0679; controls: EF 63 ± 6 RT vs 63 ± 3 CINE, Pearson r = 0.695). ConclusionRT CMR improves image quality in arrhythmic patients and renders studies more comfortable. Volumetric analysis is feasible with slightly lower values relative to CINE CMR, while ejection fractions are comparable.

Atrial Flutter Mechanism Detection Using Directed Network Mapping.

Atrial flutter (AFL) is a common atrial arrhythmia typically characterized by electrical activity propagating around specific anatomical regions. It is usually treated with catheter ablation. However, the identification of rotational activities is not straightforward, and requires an intense effort during the first phase of the electrophysiological (EP) study, i.e., the mapping phase, in which an anatomical 3D model is built and electrograms (EGMs) are recorded. In this study, we modeled the electrical propagation pattern of AFL (measured during mapping) using network theory (NT), a well-known field of research from the computer science domain. The main advantage of NT is the large number of available algorithms that can efficiently analyze the network. Using directed network mapping, we employed a cycle-finding algorithm to detect all cycles in the network, resembling the main propagation pattern of AFL. The method was tested on two subjects in sinus rhythm, six in an experimental model of in-silico simulations, and 10 subjects diagnosed with AFL who underwent a catheter ablation. The algorithm correctly detected the electrical propagation of both sinus rhythm cases and in-silico simulations. Regarding the AFL cases, arrhythmia mechanisms were either totally or partially identified in most of the cases (8 out of 10), i.e., cycles around the mitral valve, tricuspid valve and figure-of-eight reentries. The other two cases presented a poor mapping quality or a major complexity related to previous ablations, large areas of fibrotic tissue, etc. Directed network mapping represents an innovative tool that showed promising results in identifying AFL mechanisms in an automatic fashion. Further investigations are needed to assess the reliability of the method in different clinical scenarios.

Left atrial 4D flow cardiovascular magnetic resonance: a reproducibility study in sinus rhythm and atrial fibrillation

BackgroundFour-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows sophisticated quantification of left atrial (LA) blood flow, and could yield novel biomarkers of propensity for intra-cardiac thrombus formation and embolic stroke. As reproducibility is critically important to diagnostic performance, we systematically investigated technical and temporal variation of LA 4D flow in atrial fibrillation (AF) and sinus rhythm (SR).Methods Eighty-six subjects (SR, n = 64; AF, n = 22) with wide-ranging stroke risk (CHA2DS2VASc 0–6) underwent LA 4D flow assessment of peak and mean velocity, vorticity, vortex volume, and stasis. Eighty-five (99%) underwent a second acquisition within the same session, and 74 (86%) also returned at 30 (27–35) days for an interval scan. We assessed variability attributable to manual contouring (intra- and inter-observer), and subject repositioning and reacquisition of data, both within the same session (same-day scan–rescan), and over time (interval scan). Within-subject coefficients of variation (CV) and bootstrapped 95% CIs were calculated and compared.ResultsSame-day scan–rescan CVs were 6% for peak velocity, 5% for mean velocity, 7% for vorticity, 9% for vortex volume, and 10% for stasis, and were similar between SR and AF subjects (all p > 0.05). Interval-scan variability was similar to same-day scan–rescan variability for peak velocity, vorticity, and vortex volume (all p > 0.05), and higher for stasis and mean velocity (interval scan CVs of 14% and 8%, respectively, both p < 0.05). Longitudinal changes in heart rate and blood pressure at the interval scan in the same subjects were associated with significantly higher variability for LA stasis (p = 0.024), but not for the remaining flow parameters (all p > 0.05). SR subjects showed significantly greater interval-scan variability than AF patients for mean velocity, vortex volume, and stasis (all p < 0.05), but not peak velocity or vorticity (both p > 0.05).ConclusionsLA peak velocity and vorticity are the most reproducible and temporally stable novel LA 4D flow biomarkers, and are robust to changes in heart rate, blood pressure, and differences in heart rhythm.

Abstract 304: Adaptive Sarcomeric Remodeling of Left Atrial Cardiomyocytes in Non-failing Non-valvular Atrial Fibrillation

Contractile remodeling in sustained atrial fibrillation (AF) has been analyzed by limited studies whose results were confounded by either coexisting systolic heart failure or valve disease (valvular AF) or origin of tissue (right chamber instead of left, atrial appendage instead of main wall). We sought to assess the structural changes in contractile apparatus and its physiological implications on single cardiomyocyte mechanics in patients with non-failing non-valvular AF. We utilized left atrial wall tissue from rejected donor hearts from 5 subjects in sinus rhythm (SR) and 3 with AF (age 50, 2♀ vs 60, 1♀), all with no signs of cardiovascular or valvular disease. Isolated single skinned myocytes were mounted to a force transducer and length controller and set to an initial sarcomere length of 2.1 μm. Isometric active and passive forces were recorded using custom software during [Ca2+] solution switching (0.79 - 46.8 μM). Surprisingly, we found that isometric maximal calcium-activated force (Fmax) was almost two times higher in AF compared to SR patients (n: SR = 15 cells, AF = 9 cells, p &lt; 0.0001). This was unexpected, as previous studies found that AF patients had depressed contractile function, although these were confounded by heart failure and valve disease. There were no differences in calcium sensitivity, hill coefficient, or cell cross-sectional area (CSA) between SR and AF. We next performed 1D SDS-PAGE electrophoresis to compare myosin heavy chain (MHC) isoforms. In SR patients, atrial expression of β-MHC was very low (14% of total MHC expression), but this was significantly elevated in AF patients (37%, p = 0.05). The observed rise in contractile force might be a compensatory adaptation to sustain ventricular filling in initial stages of non-valvular non-failing AF patients. Or it may be a maladaptive response to atrial unloading resulting in wasted energy utilization. The contribution of this cellular increase in contractility to whole organ function is unclear. There is strong evidence that fibrotic remodeling and inflammation play an important role in AF, but the clinical challenge is still significant. Conversely, there has been very little work done on the contractile apparatus in AF, and whether it may represent a possible therapeutic target.

Normal reference values of left atrial volumes and volume-based functional properties using three-dimensional speckle-tracking echocardiography in healthy adults (Insights from the MAGYAR-Healthy Study).

The present study was designed to define normal reference values of three-dimensional speckle-tracking echocardiography (3DSTE)-derived left atrial (LA) volumes, stroke volumes (SVs), and emptying fractions (EFs) with regard to the cardiac cycle. The present study involved 256 healthy adult subjects in sinus rhythm who underwent complete two-dimensional Doppler echocardiography and 3DSTE at the same time. However, due to inferior image quality, 87 subjects have been excluded. The remaining population sample comprised of 169 patients who gave informed consent to participate in the study. While systolic maximum LA volume and early diastolic preatrial contraction LA volume did not change over age decades, late-diastolic minimum LA volume decreased and was lowest in subjects aged 40 to 49 years then increased after 50 years. Total atrial EF increased over age decades with a reduction after 50 years. Passive atrial EF showed a significant continuous increase over age decades. Active atrial EF did not change in younger ages and was the highest between ages 40 and 49 years with a significant impairment after 50 years. This study shows the age- and gender-dependency of normal values of 3DSTE-derived LA volumes, stroke volumes, and emptying fractions with regard to the cardiac cycle in healthy adult subjects.

Cardiac Computed Tomography for Atrial Fibrillation Patients Undergoing Ablation: Implications for the Prediction of Early Recurrence.

The objective of this study was to correlate early recurrence of atrial fibrillation (AF) after ablation with noninvasive imaging using cardiac computed tomography (CT). CT image data of 260 patients who had undergone wide area circumferential ablation (WACA) between October 2005 and August 2010 as well as from 30 subjects in sinus rhythm without a history of AF (control group) were retrospectively analyzed. To evaluate early outcome of AF ablation, all AF patients underwent follow-up with a 30-day event monitor 3 to 4 months after ablation. In addition, a cardiac CT was also performed 3 to 4 months after ablation to exclude pulmonary vein (PV) stenosis. The presence of early AF was correlated with anatomic and functional PV and left atrial parameters, as assessed by cardiac CT. A total of 70 patients (26.9%) were found to have early recurrence of AF. However, we found no association between PV or left atrial anatomic or functional parameters derived from cardiac imaging with early AF recurrence. Furthermore, no correlation (P>0.05) between AF recurrence and coronary artery stenosis, anatomic origin of the sinoatrial, or atrioventricular nodal arteries was observed. Finally, PV contraction did not predict AF recurrence. However, when comparing PV contraction in WACA patients with the control group, a significant (P<0.05) reduction in left superior PV and right superior PV contractility was found in patients after radiofreqency ablation. In our relatively large cohort, cardiac CT did not yield any anatomic or functional markers for the prediction of early AF recurrence after undergoing WACA. However, our data may provide insights into functional changes that occur following ablation procedures.

P1562 Normal reference values of three-dimensional speckle-tracking echocardiography-derived right atrial volumes and volume-based functional properties in healthy adult subjects

Abstract Introduction The right atrium (RA) has several roles including a systolic reservoir, early diastolic conduit and late-diastolic booster pump functions. The present study aimed to assess normal reference values of three-dimensional speckle-tracking echocardiography (3DSTE)-derived RA volumetric data and volume-based functional properties (stroke volumes, SVs and emptying fractions, EFs) in healthy adult subjects. Methods 260 healthy adult subjects in sinus rhythm with complete clinical and demographic dataset have been included in the present study. However, due to inferior image quality 110 subjects have been excluded. The remaining population comprised 150 cases (31.0 ± 11.6 years, 79 males). Complete two-dimensional Doppler echocardiography and 3DSTE have been performed in all subjects. Results While systolic maximum RA volume did not change over age decades, early and late-diastolic RA pre-atrial contraction volume and minimum RA volume increased over time. Significantly larger values could be detected in more than 50 year-old healthy subjects as compared to younger subjects. Total atrial SV remained almost unchanged over age decades with a significant reduction in subjects aged &amp;gt;50 years. Passive atrial SV showed a continuous reduction over age decades and significant difference could be demonstrated between subjects aged 18-29 years and &amp;gt;50 years. Active atrial SV increased over age decades with a significant reduction in subjects aged &amp;gt;50 years. Total atrial EF did not show any changes over age decades, but a significant reduction could be demonstrated in cases aged &amp;gt;50 years. Passive atrial EF showed significant continuous reduction over age decades. Active atrial EF did not change in younger ages, it was the highest at ages 40-49 years with a significant impairment after 50 years. Females proved to have tendentiously higher RA volumes respecting the cardiac cycle regardless of age. No significant differences could be demonstrated between RA stroke volumes between genders except between 40-49 years when females had tendentiously higher values. RA emptying fractions were non-significantly, but tendentiously higher in females as compared to that of males regardless of age. Conclusions Normal reference values of 3DSTE-derived RA volumes and volume-based functional properties and their age- and gender dependency were defined in healthy adult subjects.