Left Atrial Peak Research Articles

Abstract 11812: Cardiopulmonary Exercise Test and Atrial Fibrillation in Obstructive Hypertrophic Cardiomyopathy: A Study From Septal Myectomy Patients

Background: Cardiopulmonary exercise test (CPET )is currently used to quantify functional limitation and to evaluate the indications for surgery among patients with hypertrophic cardiomyopathy (HCM). Patients with HCM often have atrial fibrillation (AF) and their relationship is not clear. Objective: To investigate the function limitation among HCM patients who meet indications for septal myectomy and the association between it and AF. Method: We reviewed 565 consecutive patients who underwent myectomy from February 2019 to October 2021, of which 212 did CPET and 24h Holter before surgery. Results: In this cohort (median age: 50.55(37.6-58) years; male: 126(59.4%); left ventricular outflow tract gradient (LVOTG)≥ 50 mmHg: 190(89.6%)), there was a severely impaired function (Peak Oxygen consumption (Peak VO2): 16.44 ± 4.02 ml/min/kg, adjusted Peak VO2%: 58.27%). Comparing different groups divided by Peak VO2, the lowest group was characterized by older age (58 vs 50 vs 43.9 years, p < 0.001), more female patients (57.7% vs 38% vs 25.7%, p < 0.001), higher NT-proBNP level (1299 pg/ml vs 1049 pg/ml vs 742.5 pg/ml, p = 0.004), and larger left atrial diameter (46.8mm vs 43.77 mm vs 42.71 mm, p < 0.001). The incidence of AF also significantly increased (30.98% vs 14.08% vs 7.14%, p < 0.001). Among various indicators of CPET, Peak VO2 showed the strongest correlation with AF (point-biserial correlation coefficient: -0.347, p < 0.001; 0.2279, p = 0.011; -0.2502, p < 0.001; for Peak VO2, ventilatory efficiency, and anaerobic threshold, respectively). Additionally, the incidence of AF decreased with increasing severity of obstruction (60% vs 33.3% vs 16.2% vs 7.1% among non-obstructive, 30≥maximum LVOTG < 50 mmHg, 50≥LVOTG < 100 mmHg, >100 mmHg patients, respectively, p = 0.001). In multivariate regression analysis adjusting for age, sex, BMI, and left atrial diameter, Peak VO2 and LVOTG remained independently associated with the development of AF (OR 0.854, 95% CI 0.743-0.973, p = 0.021 and OR 0.969, 95% CI 0.949-0.987, p = 0.002, respectively). Conclusions: CPET indicator, particularly PeakVO2, was independently associated with the occurrence of AF in eligible surgical patients with HCM. We also found that the higher extent of obstruction, the lower the incidence of AF.

Characterization of Subclinical Cardiac Dysfunction by Speckle Tracking Echocardiography in Patients With Non-severe Acute-Phase Myocarditis

Subclinical changes in left ventricular (LV) function have been demonstrated in patients with acute-phase myocarditis (AM) despite normal LV ejection fraction. The impact of AM on right ventricular (RV) and left atrial (LA) function has not been well described. This study aimed to assess for subclinical chamber dysfunction by speckle tracking echocardiography and its clinical relevance in this population. Patients with a diagnosis of AM (as per the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases) admitted to our institution from 2013 to 2018 were assessed. Patients with elevated serum troponin, normal coronary assessment, and normal LV ejection fraction on transthoracic echocardiogram were included. Clinical and echocardiographic parameters were compared with healthy age-, gender- and risk-factor matched controls. Global longitudinal strain assessed through speckle tracking echocardiography was performed using vendor independent software (v4.6; TomTec Arena, Munich, Germany). The final cohort consisted of 80 patients (40 AM patients and 40 controls). No significant differences in baseline clinical characteristics were observed between groups. Of the echocardiographic parameters, AM patients had lower LV-global longitudinal strain (p <0.01), lower RV free-wall strain (p=0.02) and lower peak LA strain (p <0.01). There were no differences in traditional echocardiographic measures of LV, RV, and LA function appreciated between groups. The presence of multichamber involvement was associated with peak Troponin levels (p <0.01). In conclusion, our study demonstrates the presence of global subclinical myocardial dysfunction in patients with AM. Additionally, the presence of multichamber involvement was significantly associated with degree of myocardial necrosis.

Positive left atrial remodeling in patients with paroxysmal atrial fibrillation after a successful radiofrequency pulmonary vein isolation.

The potential relationship between the initial left atrial (LA) echocardiographic parameters and LA remodeling after pulmonary vein isolation with RF energy (PVI) with effectiveness of this treatment is discussed. To determine the influence of initial and after follow-up transthoracic echocardiography derived predictors of successful PVI in patients with paroxysmal atrial fibrillation (AF). 80 patients with paroxysmal AF (58 [interquartile range, IQR], 50-63] years, males: 58 [IQR, 50-63]), hospitalized for the first time PVI procedure were included. Before and after a minimum of 6 months of follow-up period a clinical and echocardiographic evaluation were performed. LA morphological parameters (diameter, volumes and other detailed LA parameters), as well as LA peak segmental and global longitudinal strains (PLS) and LA wall strain synchrony were assessed. In the whole group after a follow-up period, patients presented higher mean LA Volconduit. Patients with no AF recurrences had lower post-PVI LA volumes, higher LA ejection fraction and LA expansion index, when compared to the patients after ineffective PVI. Patients who maintained sinus rhythm after PVI procedure were characterized by a higher initial segmental strains: LA PLSbasal-inferior and PLSapical-septal, as well as higher LA wall strain dispersion in time. Some echocardiographic parameters related to LA morphology improve after successful PVI treatment. LA strains and wall strain dispersion in time are not related to LA remodeling after successful PVI procedure. However the baseline LA standard and novel echocardiographic parameters cannot be used as a remote evaluation of the effectiveness of the PVI procedure.

Left atrial subclinical dysfunction in children with Kawasaki disease: a two-dimensional speckle-tracking echocardiography study.

Left atrial (LA) function is a very important prognostic indicator for many cardiovascular diseases. In this study, we aimed to determine whether LA function is impaired in children with Kawasaki disease (KD) and to analyze the relationships between LA deformation and conventional echocardiographic parameters and laboratory markers. A total of 50 KD patients during different disease phases and 50 age- and sex-matched controls were retrospectively analyzed. Patients in the acute phase based on coronary artery dilation (CAD) were subdivided into Group I (with CAD) and Group II (without CAD) and compared. During the acute phase, KD patients had a lower peak LA longitudinal strain (PLALS), a lower LA strain peak during LA contraction (LASct), and a lower LA strain rate peak during LA contraction (LASRct) than the controls. The PLALS, LASct and LASRct began to increase during the subacute phase, and during the convalescent phase, all LA strains in patients had recovered to normal compared with the control subjects. Subgroup analysis revealed that, compared with Group II, Group I had higher C-reactive protein (CRP) and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; however, there were no significant differences in LA strains. Only the PLALS during the acute phase was negatively correlated with left ventricular mass index, CRP and NT-proBNP. In patients with KD, LA function is impaired during the acute phase, and this impairment is transient. Two-dimensional speckled tracking echocardiography is a useful tool for detecting subclinical LA dysfunction.

Paradoxical increase in left atrial strains early after Covid-19 infection, a result of comprehensive recovery phase four-chamber strains study.

Cardiac consequences of Covid-19 infection have been mentioned in various studies as a serious risk factor for in-hospital mortality. However, the existence of residual cardiac dysfunction after the acute phase is seldom investigated especially in people without a history of specific medical disease.One hundred health care workers with positive reverse transcription-polymerase chain reaction test underwent comprehensive 2D and 3D echocardiography six to eight weeks after infection. Patients were classified into Mild, Moderate, and Severe groups based on their clinical characteristics of covid-19 infection, and all echocardiographic parameters were compared between the three groups. Left ventricular (LV) stroke volume index was reduced in all groups compared to normal ranges and was more prominent in the severe group (P-value < 0.05). 3D-derived LV global longitudinal strain (GLS) was significantly lower in the severe group in comparison to the mild group (- 19.3 ± 1 Vs. - 22.2 ± 2, P-value < 0.001) and correlated with highly sensitive CRP level at the acute phase. Left atrial (LA) strains, including LA peak strain, LA contraction strain, and LA reservoir strain, were considerably higher and LA volume index was significantly lower in the clinically severe covid patients. Analysis based on the extent of lung involvement showed significantly increased 3D-derived right ventricular volumes in patients who experienced severe pneumonia despite normalized strains. Conclusion: subclinical LV dysfunction as reduced stroke volume index and GLS exists in the early recovery phase of normal individuals with severe course of covid-19. LA function indicated by LA strains paradoxically increases in severe covid-19 infection in this phase.

Left atrial stiffness and strain are novel indices of left ventricular diastolic function in children: validation followed by application in multisystem inflammatory syndrome in children due to COVID-19.

We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C). We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (-)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e' from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e'LAPeakStrain (%-1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%-1 vs. 0.17%-1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%-1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%-1 for identifying myocardial injury. In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.

Atrial strain and occult atrial fibrillation in cryptogenic stroke patients: a systematic review and meta-analysis.

Cryptogenic stroke (CS) remains a significant cause of morbidity. Failure to identify the underlying pathology increases the rate of recurrence. Atrial fibrillation (AF) seems to be responsible for a substantial proportion of CS. Thus, there is an unmet need to identify and properly treat those with silent AF. To investigate the association between left atrial strain and newly diagnosed AF in CS patients. We searched major electronic databases for articles assessing the relationship between either peak left atrial longitudinal (PALS) or peak contractile (PACS) strain-quantified using speckle tracking echocardiography-and the incidence of occult AF during the diagnostic work-up of CS patients. Eleven studies (two thousand and eighty-one patients) were analyzed. Incidence of occult AF was 19%. Both PALS and PACS were significantly lower in patients with newly diagnosed AF (MD -8.6%, 95%CI -10.7 to -6.4, I2 86.4% and MD -5.5, 95%CI -6.8 to -4.2, I2 80.8%). According to the diagnostic accuracy meta-analysis, PALS < 20% present 71% (95%CI 47-87%) sensitivity and 71% (95%CI 60-81%) specificity for the diagnosis of occult AF, assuming a prevalence of 20%. The corresponding values for PACS < 11% are 83% (95%CI 57-94%) and 78% (95%CI 56-91%). Both PALS and PACS are significantly lower in patients with CS and silent AF. It seems that the cut-off values mentioned above could help physicians in identifying patients who may benefit more from prolonged rhythm monitoring. More studies are needed to confirm these findings.

PO-455617-18 SHORT COUPLED PREMATURE ATRIAL COMPLEXES LEAD TO ADVERSE ATRIAL REMODELING AND ATRIAL FIBRILLATION IN A SWINE MODEL

Frequent premature atrial complexes (PACs) are associated with left atrial (LA) myopathy and atrial fibrillation (AF), however, the effect of coupling interval and irregularity on the ensuing atrial myopathy has not been tested. To explore the impact of coupling interval and regularity of atrial ectopics on the development of atrial remodeling and AF in a swine model. Thirty-five swine underwent baseline electrophysiologic study followed by pacemaker implantation and pacing from the lateral LA via the coronary sinus for 16 weeks in 4 groups: 1) controls without PACs (CTRL, n=10); 2) 50% paced PACs at a short coupling interval (CI) of 250ms (Short-PAC, n=10); 3) 50% PACs at a long CI of 400ms (Long-PAC, n=5); and 4) regular pacing at a faster mean atrial rate (130 beats/min) than during PACs (Reg-130, n=10). At the terminal study, a repeat electrophysiologic study was performed followed by sacrifice and histologic analysis. Structural changes: The Short-PAC group had the greater degree of LA dilation (terminal - baseline: Short-PAC 5.9±1.2cm2 vs. Long-PAC 3.9±0.5cm2 vs. Reg-130 3.0±1.0cm2 vs. CTRL 0.9±0.3cm2, p<0.001) and decrease in peak LA strain (terminal - baseline: Short-PAC -17.3±3.2% vs. Long-PAC -12.7±2.9% vs. Reg-130 -8.2±2.9% vs. CTRL -0.7±4.2%, p<0.001). Electrophysiologic changes: The Short-PAC group had slower LA conduction velocity than the Reg-130 and CTRL groups (Short-PAC 1.1±0.2m/s vs. Long-PAC 1.2±0.1m/s vs. Reg-130 1.3±0.1m/s vs. CTRL 1.5±0.2m/s, p<0.001); atrial effective refractory period (ERP) was only decreased in the Reg-130 group (terminal - baseline: Short-PAC -4.0±23.6ms vs. Long-PAC -8.7±17.9ms vs. Reg-130 -23.7±14.3ms vs. CTRL -3.2±23.7ms, p=0.09). Fibrosis: percent LA fibrosis was highest in the Short-PAC group followed by Long-PAC, Reg-130, and then CTRL groups (Figure, Panel A). AF induction: The Short-PAC group had the longest duration of induced AF (Panel B). In a swine model, frequent PACs can cause structural and electrical atrial remodeling with a heightened propensity for AF. PACs led to slow conduction and fibrosis without change in atrial ERP, suggesting a process distinct from tachy-pacing induced atrial remodeling. Moreover, PACs with short CIs resulted in a greater degree of LA remodeling and induced AF duration compared to PACs with long CIs. These findings suggest that frequent, short coupled PACs pose the highest risk for developing atrial remodeling and AF.

PO-01-001 SHORT COUPLED PREMATURE ATRIAL COMPLEXES LEAD TO ADVERSE ATRIAL REMODELING AND ATRIAL FIBRILLATION IN A SWINE MODEL

Frequent premature atrial complexes (PACs) are associated with left atrial (LA) myopathy and atrial fibrillation (AF), however, the effect of coupling interval and irregularity on the ensuing atrial myopathy has not been tested. To explore the impact of coupling interval and regularity of atrial ectopics on the development of atrial remodeling and AF in a swine model. Thirty-five swine underwent baseline electrophysiologic study followed by pacemaker implantation and pacing from the lateral LA via the coronary sinus for 16 weeks in 4 groups: 1) controls without PACs (CTRL, n=10); 2) 50% paced PACs at a short coupling interval (CI) of 250ms (Short-PAC, n=10); 3) 50% PACs at a long CI of 400ms (Long-PAC, n=5); and 4) regular pacing at a faster mean atrial rate (130 beats/min) than during PACs (Reg-130, n=10). At the terminal study, a repeat electrophysiologic study was performed followed by sacrifice and histologic analysis. Structural changes: The Short-PAC group had the greater degree of LA dilation (terminal - baseline: Short-PAC 5.9±1.2cm2 vs. Long-PAC 3.9±0.5cm2 vs. Reg-130 3.0±1.0cm2 vs. CTRL 0.9±0.3cm2, p<0.001) and decrease in peak LA strain (terminal - baseline: Short-PAC -17.3±3.2% vs. Long-PAC -12.7±2.9% vs. Reg-130 -8.2±2.9% vs. CTRL -0.7±4.2%, p<0.001). Electrophysiologic changes: The Short-PAC group had slower LA conduction velocity than the Reg-130 and CTRL groups (Short-PAC 1.1±0.2m/s vs. Long-PAC 1.2±0.1m/s vs. Reg-130 1.3±0.1m/s vs. CTRL 1.5±0.2m/s, p<0.001); atrial effective refractory period (ERP) was only decreased in the Reg-130 group (terminal - baseline: Short-PAC -4.0±23.6ms vs. Long-PAC -8.7±17.9ms vs. Reg-130 -23.7±14.3ms vs. CTRL -3.2±23.7ms, p=0.09). Fibrosis: percent LA fibrosis was highest in the Short-PAC group followed by Long-PAC, Reg-130, and then CTRL groups (Figure, Panel A). AF induction: The Short-PAC group had the longest duration of induced AF (Panel B). In a swine model, frequent PACs can cause structural and electrical atrial remodeling with a heightened propensity for AF. PACs led to slow conduction and fibrosis without change in atrial ERP, suggesting a process distinct from tachy-pacing induced atrial remodeling. Moreover, PACs with short CIs resulted in a greater degree of LA remodeling and induced AF duration compared to PACs with long CIs. These findings suggest that frequent, short coupled PACs pose the highest risk for developing atrial remodeling and AF.

Echocardiographic Measures of Left Atrial Structure and Function and the Association with Atrial Fibrillation following Acute Coronary Syndrome

Introduction: Acute coronary syndrome (ACS) is associated with an increased risk of developing atrial fibrillation (AF). This arrhythmia is associated with adverse outcomes, making it important to identify high-risk patients. The aim was to evaluate the prognostic value of measures of left atrial (LA) structure and function in AF prediction following ACS. Methods: Three hundred and eighty-one patients who had a percutaneous coronary intervention for ACS were included in the study. Our endpoint was new-onset AF. Results: With a median follow-up time of 5.4 [3.9–6.8] years, 56 patients (14.7%) developed AF. Patients developing AF had significantly (p ≤ 0.05) increased maximal and minimal LA volumes (LAV_max and LAV_min, respectively). LAV_max and LAV_min remained significantly increased in AF patients when indexing to either body surface area (LAV_max/BSA and LAV_min/BSA, respectively), left ventricle length in end diastole (LAV_max/LVLd and LAV_min/LVLd, respectively), or late mitral annular diastolic velocity (LAV_max/a’ and LAV_min/a’, respectively), while LA expansion index (LAEi), LA emptying fraction (LAEF), and peak LA longitudinal strain (PALS) were decreased. In univariable Cox regressions, all LA measures were found to be predictors of AF. After multivariable adjustment for clinical and echocardiographic parameters, all measures reflecting atrial function (LAV_min, LAV_min/BSA, LAV_min/LVLd, LAV_min/a’, LAV_max/a’, LAEF, LAEi, and PALS) (p ≤ 0.05) but no structural measures (LAV_max, LAV_max/BSA, and LAV_max/LVLd) remained significant independent predictors of AF. Conclusion: Echocardiographic measures of LA function are independent predictors of AF following ACS. Evaluation of LA function might improve the prognostic workup, aid in risk stratification for AF, and improve selection for further examinations.

Left Atrial Functional Remodeling in Patients with Chronic Heart Failure Treated with Sacubitril/Valsartan.

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR-). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (-9.7 ± 5.2% vs. -7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined.

Change in minimum indexed left atrial volume predicts incident heart failure: the multi-ethnic study of atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: None. Background and Purpose Longitudinal change in the left atrium prior to the onset of heart failure has not been as well studied as left atrial (LA) dysfunction in pre-existing heart failure. This study used cardiac magnetic resonance (CMR) imaging to investigate the relationship between longitudinal change in LA volume and function and incident heart failure (HF), in a multi-ethnic population free of known cardiovascular disease at baseline. Methods and Results In the Multi-Ethnic Study of Atherosclerosis (MESA), 2470 participants (60±9 years, 47% males), free at baseline of clinically recognized cardiovascular disease, had LA volume, emptying fractions and peak longitudinal strain assessed with Multimodality Tissue Tracking (MTT; version 6.0 Toshiba, Japan) on CMR imaging at baseline (2000-02) and at follow-up 9.4±0.6 years later. Seventy three (3%) participants subsequently developed incident HF 7.1±2.1 years after the follow-up CMR exam. In cox regression models, an annualized change in all LA parameters were significantly associated with an increased risk of incident HF. An annual increase of 1ml/m2 in minimum indexed LA volumes (∆LAVimin) was most strongly associated with the risk of incident HF (Hazard Ratio(HR)=1.85, 95% confidence interval(CI) [1.49-2.29], P&amp;lt;0.001) and improved model reclassification and discrimination in predicting incident HF (c-statistic=0.80, 95%CI [0.75-0.86]; NRI=0.13, P=0.04; IDI=0.04, P=0.01; x2=6.52, P=0.69) adjusting for known risk factors (age, gender, systolic blood pressure, anti-hypertensive medication use, smoking status, diabetes mellitus, total cholesterol, previous atrial fibrillation) and baseline LA parameters. Conclusion In this multi-ethnic population free of clinical cardiovascular disease at baseline, ∆LAVimin was most strongly associated with, and incrementally predictive of incident HF, after adjusting for known risk factors and baseline LA measures.

Prognostic Significance of Cardiac Magnetic Resonance in Left Atrial and Biventricular Strain Analysis during the Follow-Up of Suspected Myocarditis.

To assess the variation in left atrial (LA) and biventricular strain and its prognostic value in the course of suspected myocarditis, this retrospective study included 55 patients with clinically suspected myocarditis who underwent cardiac magnetic resonance (CMR) examinations at baseline and follow-up periods. Cine images were used for feature tracking analysis. Paired Student's t test, McNemar's test, and Cox proportional hazard regression were used for statistical analysis. The LA total emptying fraction was the only functional index that showed a statistically significant improvement. The initial LA peak's late negative strain rate (SRa) was the only parameter with a significant predictive power of major adverse cardiac events under univariable (hazard ratio [HR] 2.396, 95% confidence interval [CI] 1.044-5.498, p = 0.039) and multivariable Cox survival analysis when adjusted by LA strain parameters (HR 5.072, 95% CI 1.478-17.404, p = 0.010), LA strain and functional parameters (HR 7.197, 95% CI 1.679-30.846, p = 0.008), and LA and biventricular strain and functional parameters (HR 10.389, 95% CI 2.250-47.977, p = 0.003). Thus, our findings indicate that CMR strain is useful for monitoring LA and ventricular function in suspected myocarditis, that LA function may recover preceding ventricular function changes, and that LA strain may serve as an incremental tool to predict adverse outcomes.

Response to 'Is the left atrium the key in the amyloid imaging lock?'

We thank Dr Bart for her commentary on our paper.1 The echocardiogram is the first-line imaging technique in patients with suspected cardiac amyloidosis (CA).2 Speckle-tracking analysis of the left ventricle should be systematically performed, as the apical sparing pattern is strongly suggestive of CA, particularly in individuals with unexplained hypertrophy.2 In patients in sinus rhythm, the left atrial (LA) function may be studies by calculating the peak LA longitudinal strain (PALS), which reflects the reservoir function, and peak LA contraction strain (PACS), which explores the contractile function of the LA. In our study, we reported that both PALS and PACS are severely depressed in patients with amyloid transthyretin (ATTR) CA.3 The mechanisms are (i) a progressive dilation and remodelling of the LA, due to diastolic dysfunction and leading to a depressed LA contractility, and (ii) amyloid deposition in the atrial walls, with an expansion of extracellular spaces and cardiomyocyte dysfunction. Structural and functional remodelling of the LA is more prominent in ATTR-CA, which is a slowly progressive disease, than in amyloid light-chain (AL)-CA, which has a more rapid progression.3 We agree with Dr Bart that this difference between ATTR- and AL-CA may be useful for the purposes of differential diagnosis. The exact role of cardiovascular magnetic resonance (CMR) in the diagnostic workup of CA has not been standardized yet, but CMR may implement baseline examination in patients with suspected CA. Several techniques (feature tracking, tagging, and tissue-phase contrast) allow to track the motion of LA throughout the cardiac cycle and represent the CMR equivalents of speckle-tracking imaging. The study cited by Dr Bart investigated the value of CMR-based LA strain in 54 patients with CA (30 AL and 24 ATTR), reporting a lower LA function in patients with ATTR vs. AL despite no significant differences in LA geometry.4 These findings are in agreement with our study.1 Echo- or CMR-based LA strain might then help differentiate AL- from ATTR-CA among patients starting the diagnostic workup for suspected CA. On the other hand, further investigations (cardiac scintigraphy with bone tracers, search for a monoclonal protein, and often histological analyses) are still needed to confirm the diagnosis of CA and its subtype, in agreement with the current algorithm.1 Beyond its possible diagnostic value, we think that LA strain might prove helpful for risk stratification and to track disease evolution. A more depressed LA strain is reasonably associated with more blood stasis and a greater risk of atrial thrombosis, and could then suggest the potential need for an anticoagulant therapy even when there is no history of atrial fibrillation.1,2 As for the second point, LA strain has a close association with disease severity and is highly reproducible, meaning that a deterioration of LA strain over time reflects disease progression, while unchanged or improved values over times may mirror the stabilizing or positive effects of disease-modifying therapies.5 In summary, LA strain could really become a ‘key in the amyloid imaging lock’.

Could echocardiographic left atrial characterization have additive value for detecting risks of atrial arrhythmias and stroke in patients with hypertrophic cardiomyopathy?

Abstract Background Atrial arrhythmia (AA) is considered a turning point for prognosis in hypertrophic cardiomyopathy (HCM) patients. Prediction of AA and associated stroke risk in patients with HCM is an important clinical challenge as these events can occur in young subjects and significantly impact their quality of life. (1) (2) Purpose We sought to assess whether an echocardiographic evaluation focused on the left atrial (LA) characterization could estimate the occurrence of AA and stroke in HCM patients. Methods 216 HCM-patients (52±16 years old) were enrolled between 2016 and 2019. All patients underwent transthoracic echocardiography for the evaluation of left atrial volume (LAV), left ventricular global longitudinal strain (LV-GLS), peak left atrial strain (PLAS) and peak atrial contraction strain (PACS) by speckle-tracking imaging. A composite endpoint was defined as a history of AA and/or a history of stroke or peripheral embolism and/or occurrence of AA. Results The patients were followed for 2.9 years. Among the 216 patients, 78 (36%) met the composite endpoint. These patients were older (50.3±16.7 vs. 57.1±14.4 years, p=0.0035), had a higher prevalence of arterial hypertension (42.3% vs. 62.3%; p=0.005) and had higher NT-proBNP levels. LAV (37.2±15.7 vs. 47±20 ml/m2, p=0.0001) was significantly higher in patients who met the composite endpoint, whereas PLAS and PACS were significantly impaired (26.6±9.12 vs. 19.3±9.54%; p&amp;lt;0.0001 and 13.1±6.3% vs. 8.8±6.5%; p&amp;lt;0.0001, respectively). After adjustment, PLAS and PACS remained independently associated with events with an odds ratio (OR) of 0.42 for PLAS (95% CI, [0.29–0.61]; p&amp;lt;0.0001). Stroke occurred in 67% of the patients without any clinical AA. PLAS with a cut-off of under 15.5% provided event detection with 91% specificity and demonstrated a predictive value for new-onset of AA. Although there was a high correlation between PLAS and LV-GLS, LV-GLS was not associated with the events. Conclusion The impairment of LA function assessed by 2D speckle-tracking echocardiography was strongly associated with AA and the risk of stroke, even in patients without any documented AA. Its value for guiding the management of HCM-patients requires further investigation. Funding Acknowledgement Type of funding sources: None.

Signals for reduced cognitive function are associated with subtle signs of atrial cardiomyopathy and left ventricular diastolic dysfunction – insights from a large population based study

Abstract Background/Introduction In recent years, it has been proposed that a thrombogenic atrial substrate due to various alterations in (left) atrial morphology and function could contribute to atrial thromboembolism even in the absence of (clinically overt) atrial fibrillation. This so-called atrial cardiomyopathy may pose a risk of stroke and cognitive decline beyond the presence of atrial fibrillation. Purpose To define the association of echocardiographic parameters of left atrial cardiomyopathy and left ventricular diastolic dysfunction with cognitive function in individuals free of clinically overt atrial fibrillation or stroke. Methods Data from the first 10,000 participants of a large German population-based cohort study were analysed. Of these, 8264 individuals underwent standardized transthoracic echocardiography and cognitive function testing at baseline. Parameters of left ventricular systolic and diastolic function as well as left atrial function were systematically assessed, including left atrial global peak strain. Cognitive function was quantified using the Animal Naming Test and the Trail Making Test A and B. We performed linear regression analyses with incremental adjustment to examine the association of echocardiographic parameters with the performance on the neuropsychological tests. Results After exclusion of 463 individuals with known AF and 309 individuals with prior/known stroke or severe depression, 7492 individuals were analysed (mean age 61.9±8.4 years, 52.3% women, median left ventricular ejection fraction 59% [25th/75th percentile 56/62%], median left atrial volume index 25.0 ml/m2 [25th/75th percentile 20/30 ml/m2]). In multivariable-adjusted analyses, E/e'-ratio was significantly associated with a worse performance on the Animal Naming Test (−0.24 per one standard deviation [SD] increase, 95% confidence interval [CI] −0.42 to −0.06), the Trail Making Test A (0.76 per one SD increase, 95% CI 0.35–1.17) and B (1.1 per one SD increase, 95% CI 0.09–2.11). Left atrial strain was associated with worse performance on Trail Making Test B (−1.39 per one SD increase, 95% CI −2.46 to −0.32). Increased left atrial volume index was associated with worse performance on the ANT (0.2, 95% CI 0.03–0.37). Conclusions Subtle echocardiographic signs of atrial cardiomyopathy and left ventricular diastolic dysfunction are associated with worse performance on cognitive function tests in a German middle-aged population. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): The Hamburg City Health Study (HCHS) is supported by the University Medical Center Hamburg-Eppendorf and by various grants from different institutions/organizations.

The Mueller maneuver attenuates left atrial phasic volumes and myocardial strain in healthy younger adults

Abstract Background Negative intrathoracic pressure swings alter cardiac loading conditions, which may impact left atrial hemodynamic function and augment atrial stress. If such changes occur and are repeated chronically, they may contribute to the marked atrial remodeling seen in states associated with forceful inspiratory efforts such as endurance training or obstructive sleep apnea. Purpose We studied the acute effects of static inspiratory efforts on left atrial chamber function, myocardial mechanics, and diastolic function. Methods We included healthy adults (10M/7F, 24±4 years) and used Mueller maneuvers to reduce intrathoracic pressure to a −30 cmH2O target for 15 seconds. Over 6 repeated trials, we used echocardiography to acquire left atrial and ventricular focused 2D images, and mitral Doppler inflow and annular tissue velocity spectra. Images were analyzed offline to determine left ventricular volumes, tissue relaxation velocities, trans-mitral filling velocities, and phasic left atrial volumes and myocardial strain using speckle-tracking imaging. Repeated measures were made at Baseline, within the last 5 seconds of the Mueller maneuver, and within the first 5 seconds after release, with 3–5 cardiac cycles averaged per measurement. Results Compared to Baseline, hemodynamic changes occurred during the late phase of the Mueller maneuver and immediately after release. Left ventricular stroke volume decreased by −10±4 mL (p&amp;lt;0.05) then returned to baseline upon release; this was associated with a −11±9 mL (p&amp;lt;0.05) reduction in end-diastolic volume. Left ventricular early diastolic filling attenuated, reflected by decreases in mitral annular relaxation velocity (−2±2 cm/s, p&amp;lt;0.05), E-wave filling velocity (−13±14 cm/s, p&amp;lt;0.05), and left atrial passive emptying volume (−5±5 mL, p&amp;lt;0.05), each normalizing upon release. Left atrial maximal volume decreased (−5±5 mL, p&amp;lt;0.05) during the Mueller maneuver, but increased relative to baseline (+4±5 mL, p=0.049) following release, while left atrial peak positive longitudinal strain decreased (−6±6%, p&amp;lt;0.05) and normalized upon release. Conclusions Attenuated left atrial and in turn ventricular filling may contribute to acute stroke volume reduction during forceful inspiratory efforts. Rapid changes in left atrial chamber volumes and myocardial strain with the release of forceful inspiratory efforts may reflect acute left atrial stress. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Natural Sciences and Engineering Research Council Discovery Grant

Impact of left atrial size and strain on new atrial arrhythmias during a 5-year follow-up in adults with congenital heart disease

Abstract Introduction Atrial arrhythmias are a common and important cause of morbidity and mortality in adults with congenital heart disease (ACHD). In acquired heart disease, left atrial (LA) strain has been shown to predict supraventricular tachyarrhythmias (SVT). This study sought to investigate if LA strain is also a reliable predictor of SVT in the ACHD population. Method We retrospectively obtained baseline clinical and echocardiographic data, including LA function parameters and strain, in 206 ACHD patients. Only patients with sinus rhythm at baseline and 5-years follow-up were included (median age 29, IQR 22–41 years). 157 participants had a left heart defect (aortic stenosis or aortic coarctation, with or without correction) and 49 a right heart defect (Fallot physiology). Diagnosis of sustained SVT was determined from clinical reports during the follow-up period (standard 12-lead ECG, ECG Holter). Results During a median follow-up of 6.2 years, a new or recurrent sustained SVT occurred in 16 patients (7.8%). Patients baseline characteristics are depicted in Table 1. Patients who developed SVT were older, had larger LA dimensions and left ventricular mass, more likely diastolic dysfunction on echo, and a lower peak LA longitudinal strain (PALS). PALS was a good predictor of SVT risk in patients with left and right heart defects with an area under the receiver-operating-curve of 0.857. By Cox regression analysis, patient in the lowest quartile for PALS had a 16.7-fold higher hazard ratio of SVT (95% confidence interval, 4.7 to 59.0, p&amp;lt;0.001) in comparison with the top three quartiles. Overall freedom from arrhythmia after 1, 3 and 5 years of follow-up was 98.1%, 96.1% and 94.2%, respectively. The freedom from SVT as a function of PALS quartiles is shown in Figure 1. Conclusion PALS provides predictive information about the occurrence of SVT in the ACHD population, regardless of the type of the lesion. Including the measurement of LA strain in the follow-up of these patients may permit to better identify patients at risk of future atrial arrhythmias. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Universitätsklinik für Kardiologie, Inselspital Bern

Change in left atrial function and volume predicts heart failure with preserved and reduced ejection fraction: the multi-ethnic study of atherosclerosis

Abstract Aims This study used cardiac magnetic resonance (CMR) imaging to investigate the relationship between longitudinal change in left atrial (LA) function and incident heart failure (HF), in a multi-ethnic population free of known cardiovascular disease at baseline. Methods and results In the Multi-Ethnic Study of Atherosclerosis (MESA), 2470 participants (60±9 years, 47% males), free at baseline of clinically recognized cardiovascular disease, had LA volume and function assessed with CMR imaging at baseline (2000–02) and 9.4±0.6 years later. Seventy three (3%) participants developed incident HF over 7.1±2.1 years; of these, 39 participants had preserved ejection fraction (HFpEF) and 34 participants had reduced ejection fraction (HFrEF). An annual decrease of 1-SD unit in peak LA strain (ΔLASmax) was most strongly associated with the risk of HFpEF (subdistribution HR=2.56, 95% confidence interval (CI) [1.34–4.90], P=0.004) and improved model reclassification and discrimination in predicting HFpEF (c-statistic=0.84, 95% CI [0.79–0.90]; NRI=0.34, P=0.01; IDI=0.02, P=0.02; x2=4.25, P=0.89) adjusting for event-specific risk factors and baseline LA parameters. An annual decrease of 1ml/m2 of pre-atrial LA volume index (ΔLAVipreA) was most strongly associated with the risk of HFrEF (subdistribution HR=1.88, 95% CI [1.44–2.45], P&amp;lt;0.001) and improved model reclassification and discrimination in predicting HFrEF (c-statistic=0.81, 95% CI (0.72–0.90); NRI=0.31, P=0.03; IDI=0.01, P=0.50; x2=15.4, P=0.08), adjusting for event-specific risk factors and baseline LA measures (Table 1). Conclusion In this multi-ethnic population free of clinical cardiovascular disease at baseline, ΔLASmax and ΔLAVipreA were associated with, and incrementally predictive of HFpEF and HFrEF respectively, after adjusting for event-specific risk factors and baseline LA measures. Disclaimer The views expressed in this abstract are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Heart, Lung and Blood InstituteNational Center for Advancing Translational Sciences

Blunted atrial reverse remodeling a year after catheter ablation for atrial fibrillation and their long-term rhythm outcome

Abstract Background Although active rhythm control by atrial fibrillation (AF) catheter ablation (AFCA) reduces left atrial (LA) dimension, blunted atrial reverse remodeling can be observed in patients with significant atrial myopathy. We explored the characteristics and long-term outcomes of AF patients who showed blunted atrial reverse remodeling despite no AF recurrence within a year after AFCA. Methods Among a total of 2,756 patients with AFCA, we included 1,685 patients (74.8% male, 60.2±10.1 years old, 54.5% paroxysmal AF) who underwent both baseline and 1-year follow-up echocardiogram, baseline LA&amp;gt;40mm, and did not recur within a year. We divided them into tertile groups (T1–T3) based on one-year percent change of LA dimension after propensity matching for age, sex, AF type, and baseline LA dimension. We also investigated the patients' genetic characteristics with blunted LA reverse remodeling (T1) using a genome-wide association study (GWAS). Results Patients with blunted LA reverse remodeling (T1, n=424) were independently associated with body mass index (OR 1.082 [1.010–1.160], p=0.025), LA peak pressure (OR 1.010 [1.002–1.019], p=0.019), LA wall thickness (OR 0.448 [0.252–0.789], p=0.006), LA voltage (OR 0.651 [0.463–0.907], p=0.012), and pericardial fat volume (OR 1.004 [1.001–1.008], p=0.014). Throughout 65.9±37.4 months of follow-up, the incidence of AF recurrence a year after the procedure was significantly higher in the T1 group than in T2 or T3 groups (Log-rank p&amp;lt;0.001). Among 894 patients with GWAS, ATXN1, XPO7, KRR1_PHLDA1, ZFHX3, and their polygenic risk score were associated with blunted LA reverse remodeling. Conclusions Patients with blunted LA reverse remodeling after AFCA were independently associated with low LA voltage, thin wall thickness, high LA pressure, and fat volume, and have a genetic background. Long-term clinical recurrence a year after AFCA was higher in this patient group with suspicious atrial myopathy. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health and WelfareNational Research Foundation of Korea