Left Atrium Dysfunction Research Articles

Is left atrial reservoir strain a superior modality to predict acute left ventricular failure in hypertensive patients

Abstract Background The left atrium (LA) plays an important role in the pathophysiology of heart failure. Left Atrial function has 3 components and their relative contributions, under normal circumstance, include reservoir(40%), conduit (35%), and active pump(25%) function(1). All these functions can be assessed by their respective strain, measured in trans thoracic echocardiography usually by speckle tracking, from apical 4 and 2 chamber views. Of the 3 types of LA strain, LA reservoir strain (LAS-r), is the best reflection of atrial function(2). LA strain can detect LA dysfunction even before obvious LA enlargement, aiding preclinical diagnosis of cardiac dysfunction. Purpose To assess if Left atrial reservoir strain was a superior modality to predict acute Left Ventricular Failure in hypertensive patients. Methodology Our study cohort consisted of 200 hypertensive patients, 84 females and 116 males, 40 to 71 years old with hypertension duration of 6 months to 21 years .Patients with other co morbidities were excluded. All were on treatment and had BP ranging from normal to high. Sixty two (31%) had experienced one or more episodes of acute left ventricular failure(LVF). Patients underwent in addition to routine investigations, detailed ECHO including measurement of left ventricular global longitudinal strain(LVGLS- normal > -18) and LAS-r (Normal >35). Results and Discussions All patients had normal ejection fraction. 128 (64%) had LVDD. 102(79.8%) had grade 1 LVDD, 24 (18.6%) had grade II LVDD and 2 (1.6%) had Grade III. Forty eight (37.5%) of the 128 with LVDD experienced acute LVF and 23(47.9%) of them had grade 11 LVDD or more. Forty two (21%) had reduced LVGLS, of these, 18(42.9%) experienced acute LVF and of these, 14(77.8%) had in addition reduced LAS-r. One hundred and two (51%) had reduced LAS-r (LAS-r <25), of which 61(59.8%) had experienced acute LVF. 63(31.5%) had increased LA volume of which 37( 58.7%) had experienced acute LVF. 5.7% of patients with BP <150/90 had reduced LAS-r, 69.5% with BP between 150/90- 169/100 had reduced LAS-r and 85.4% with BP > 170 had reduced LAS-r. Of the 62 patients with acute LVF, 18(29%) showed reduced LVGLS, 48(77.4%) had LVDD, 37(59.7%) had increased LA volume and 61(98.4%) had reduced LAS-r indicating that the latter was an earlier, better predictor of acute LVF than the former three. Although there were no age or gender differences in the findings, the prevalence of reduced LAS-r was higher with less well controlled BP. Conclusions In our study, LAS-r, irrespective of the age or sex, was an earlier better predictor of acute LVF than reduction of LVGLS, LVDD or increased LA volumes, in hypertensive patients. The prevalence of reduced LAS-r was higher in patients with poorly controlled BP. Prognostic significance of LAS-r can help influence early clinical decision making and for defining early management.TABLE 1TABLE 2

Human epicardial adipose tissue-derived factors promote atrial endothelial dysfunction: role of pro-inflammatory cytokines and AT1R/NADPH oxidases/SGLT2 pro-oxidant pathway

Abstract Introduction Epicardial adipose tissue (EAT) has been suggested to contribute to left atrium dysfunction via paracrine mechanisms to induce endothelial dysfunction, pro-arrhythmogenic and pro-remodeling responses thereby favoring atrial fibrillation (AF) onset. Recently, sodium-glucose co-transporter2 inhibitors (SGLT2i) have been shown to reduce AF incidence, EAT volume, differentiation and inflammation, however, the underlying mechanisms are unknown. Purpose This study investigates the impact of human EAT-derived mediators on atrial endothelial cell function and, if so, to characterize the role of SGLT2 using the inhibitor empagliflozin (EMPA). Methods Epicardial and subcutaneous adipose tissues (SAT) were collected from 70 cardiac patients at a university hospital. Conditioned medium (CM, 24 h) from fats were applied to porcine atrial endothelial cells (AECs, first passage) for 24 h. Histology of tissues was assessed by haematoxylin and eosin staining, protein expression by Western blot analysis or immunofluorescence staining, mRNA levels by RT-qPCR, formation of reactive oxygen species (ROS) and nitric oxide (NO) by fluorescent probes, and pro-inflammatory cytokine levels by ELISA. Results Compared to SAT, EATs were more vascularized with increased infiltration of M1-like macrophages, expression of proinflammatory cytokines (IL-1ß, IL-6, TNF-α), markers of ECs VCAM-1 and eNOS, fibrosis TGF-β, NADPH oxidases NOX-1 and SGLT1/2. These effects were associated with a pro-oxidant response that was inhibited by neutralizing Abs directed against IL-1ß or IL-6, and by inhibition of either NOS, NADPH oxidases, ACE, AT1R or SGLT2. Levels of SGLT2 and ROS in EATs were higher in AF compared to non-AF patients and progressively increasing with age. CM of EATs showed higher concentrations of IL-1ß, IL-6, TNF-α and MCP-1 than that of SAT. Exposure of AECs to CM of EATs increased the level of oxidative stress that was positively correlated to the level of pro-inflammatory cytokines, and reduced basal and bradykinin-induced NO formation that was prevented by EMPA. It also resulted in upregulation of p53 and SGLT2 expression, and nuclear translocation of NF-kB by CM of the top quartile inflamed EATs but not by the lowest quartile of EATs or SATs, prevented by EMPA. Conclusion The findings indicate that compared to SATs, the EATs showed higher in situ expression and release of pro-inflammatory cytokines that contributed to oxidative stress involving the AT1R/NADPH oxidases/SGLT2 pro-oxidant pathway. CMs of inflamed EATs induced AECs dysfunction, oxidative stress and activation of NF-kB involving pro-inflammatory cytokines and SGLT2. Thus, SGLT2i appear as an interesting strategy to decrease EAT inflammation and improve endothelial function contributing to prevent cardiac remodeling and fibrotic responses.

Takotsubo syndrome: left atrial and ventricular myocardial strain impairment in the subacute and convalescent phases assessed by CMR.

We investigated the differences in impairment of left ventricle (LV) and left atrium (LA) contractile dysfunction between subacute and convalescent takotsubo syndrome (TTS), using myocardial strain analysis by cardiac magnetic resonance (CMR) feature-tracking technique. We retrospectively selected 50 patients with TTS clinical-radiological diagnosis who underwent CMR within 30days since symptoms onset: 19 studied during the early subacute phase (sTTS, ≤ 7days) and 31 during the convalescence (cTTS, 8-30days). We measured the following: LV global longitudinal, circumferential, and radial strain (lvGLS, lvGCS, lvGRS) and strain rate (SR) and LA reservoir (laS_r), conduit (laS_cd), and booster pump strain (laS_bp) and strain rate (laSR_r, laSR_cd, laSR_bp). Patients were compared with 30 age- and sex-matched controls. All patients were women (mean age 63years). TTS patients showed altered LV- and LA-strain features, compared to controls. sTTS was associated with increased laS_bp (12.7% versus 9.8%) and reduced lvEF (47.4% versus 54.8%), lvGLS (-12.2% versus 14.6%), and laS_cd (7.0% versus 9.5%) compared to cTTS (p ≤ 0.029). The interval between symptoms onset and CMR was correlated with laS_bp (r = -0.49) and lvGLS (r = 0.47) (p = 0.001 for both). At receiver operating characteristics analysis, laS_bp was the best discriminator between sTTS and cTTS (area under the curve [AUC] 0.815), followed by lvGLS (AUC 0.670). LA dysfunction persists during the subacute and convalescence of TTS. laS_bp increases in subacute phase with progressive decrease during convalescence, representing a compensatory mechanism of LV dysfunction and thus a useful index of functional recovery. Atrial strain has the potential to enhance the delineation of cardiac injury and functional impairment in TTS patients, assisting in the identification of individuals at higher risk and facilitating the implementation of more targeted and personalized medical therapies. • In TTS, after ventricular recovery, atrial dysfunction persists assessable with CMR feature tracking. • Quantitative assessment of atrial strain discriminates atrial functions: reservoir, conduit, and booster pump. • Atrial booster pump changes after acute TTS, regardless of ventricular function. • Atrial strain may serve as a temporal marker in TTS.

Effect of late gadolinium enhancement on left atrial impairment in myocarditis patients

ObjectiveThe aims of our study were to investigate the effect of the extent and location of late gadolinium enhancement (LGE) on the left atrium (LA) function in patients with acute myocarditis (AM) using cardiovascular magnetic resonance (CMR).MethodThis retrospective study performed CMR scans in 113 consecutive patients (89 males, 24 females; mean age 45.8 ± 17.3 years) with AM that met the updated Lake Louise criteria. Reservoir, conduit, and booster LA functions were analyzed by CMR feature tracking using dedicated software. Besides LA strain measurements, myocardial scar location and extent were assigned and quantified by LGE imaging.ResultsAM patients with septal LGE had impaired reservoir, conduit, and conduit strain rate function in comparison with AM patients with non-septal LGE (p = 0.001, for all). In fully adjusted multivariable linear regression, reservoir and conduit were significantly associated with left ventricle (LV) LGE location (β coefficient = 8.205, p = 0.007; β coefficient = 5.185, p = 0.026; respectively). In addition, LA parameters decreased according to the increase in the extent of LV fibrosis (LGE ≤ 10%; LGE 11–19%; LGE ≥ 20%). After adjustment in multivariable linear regression, the association with LV LGE extent was no longer statistically significant.ConclusionIn patients with acute myocarditis, LA function abnormalities are significantly associated with LV LGE location, but not with LGE extent. Septal LGE is paralleled by a deterioration of LA reservoir and conduit function.Clinical relevance statementLeft atrium dysfunction is associated with the presence of late gadolinium enhancement in the left ventricle septum and can be useful in the clinical prognostication of patients with acute myocarditis, allowing individually tailored treatment.Key Points• Myocardial fibrosis is related to atrial impairment.• The location of myocardial fibrosis is the main determinant of atrial dysfunction in myocarditis patients.• The quantification of atrial mechanisms may provide more in-depth insight into myocarditis pathophysiology.

Left Atrial Myopathy in Heart Failure With Preserved Ejection Fraction.

The left atrium (LA) plays an important role in facilitating left ventricular (LV) filling by acting as a reservoir, passive conduit, and active booster pump, as well as a regulator of blood volume through A-type natriuretic peptide secretion in response to stimulation by mechanical stretch of the cavity. LA myopathy has emerged as one of the most important non-LV contributors to disease progression in heart failure with preserved ejection fraction (HFpEF). LA dysfunction is common in HFpEF and is associated with more severe pulmonary vascular disease and right ventricular dysfunction, and increases the risk of incident atrial fibrillation or atrial functional mitral regurgitation, leading to limitations in cardiac output reserve and reduced exercise capacity. LA deformation assessed by 2-dimensional speckle-tracking echocardiography is useful for estimating abnormal hemodynamics or exercise capacity, discriminating HFpEF from non-cardiac dyspnea and is an independent predictor of adverse outcome in HFpEF. Thus, interventions directly targeting LA myopathy may improve outcomes in HFpEF with LA myopathy. This review provides information regarding the physiology of the LA in patients with HFpEF and discusses the importance of evaluation of LA function, management issues, and future directions through ongoing trials of medical interventions.

The impact of continuous positive airway pressure therapy on left atrial function assessed by 2D speckle tracking echocardiography in patients with obstructive sleep apnoea

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Obstructive sleep apnoea (OSA) is associated with left atrium (LA) remodelling and dysfunction, developing even before left ventricle (LV) hypertrophy and diastolic dysfunction. Two-dimensional speckle-tracking echocardiography (2D-STE) may help to detect subclinical LA dysfunction before irreversible cardiac changes. Purpose To evaluate changes of LA geometry and function after short term continuous positive airway pressure therapy (CPAP) for OSA using 2D-STE. Methods 47 obese patients aged between 18 to 65 years old were enrolled in the study. Control group (N=13) consisted of healthy subjects who either did not have OSA, or it was mild (apnea/hypopnea index (AHI) 5 – 14/ hour). OSA group (N=34) consisted of subjects with moderate or severe OSA (AHI ≥ 15/ hour). Transthoracic echocardiography and 2D STE analysis performed before and after 3 months of treatment with CPAP, for control group – at a baseline only. Statistical analyses were performed using the SPSS 27.0 software. The value of p<0.05 was considered as statistically significant. Results Control group was younger, had more female patients, and prevalence of arterial hypertension was lower compared to OSA group. All patients had preserved LV EF (>50 %) without significant differences between groups. OSA was related to more prevalent LV diastolic dysfunction (p = 0.023) and increased LV myocardial mass when indexed by height (46.11 (8.23) vs 38.96 (5.9) g/m 2.7, p = 0.007). OSA patients had significantly higher LA diameter (43.58 (8.19) vs 36.23 (3.08) mm, p <0.001), while LA volume did not differ even when indexed by height (p>0.05). LA reservoir strain was significantly lower in patients with OSA (26.56 (1.38) vs 31.01 (1.56) %, p<0.001) when compared to control group. After 3 months of CPAP treatment LA diameter, LA volume, LV MMi, LA conduit and contractile strain did not change , but prevalence of LV diastolic dysfunction decreased and LA reservoir strain improved. (Table 1). Conclusions Our study showed more prevalent LV diastolic dysfunction, increased LV myocardial mass indexed by height, together with reduced LA reservoir strain in OSA patients with preserved LV ejection fraction. Short term CPAP treatment significantly improved LV diastolic function and LA reservoir strain in OSA patients.

Left Atrial Remodeling in Patients With Severe Rheumatic Mitral Stenosis and Sinus Rhythm Using Two-Dimensional and Three-Dimensional Speckle Tracking Echocardiography

In mitral stenosis (MS), the combination of an increase in left atrium (LA) pressure and atrial inflammatory response is accompanied by increase in interstitial fibrosis of the atrial wall with disorganization of atrial muscle bundles, LA dysfunction and subsequently LA dilatation. We aimed to assess the effect of severe rheumatic MS on LA volumes and mechanics. We enrolled 40 patients with pure severe rheumatic MS and sinus rhythm as a patient group and 30 healthy subjects as a control group. All patient and control groups underwent two-dimensional (2D) transthoracic echo to measure left ventricle (LV) dimensions, function, LA deformations, estimated systolic pulmonary artery pressure (EPAP), and left ventricle global longitudinal strain (LV GLS). Also LA volumes and mechanics (LA strain during LV systole (reservoir function) and LV diastole (early = conduit, and late = booster pump = atrial contraction)) were measured by three-dimensional (3D) transthoracic echo; mitral valve (MV) area was measured by 3D transesophageal echo (as routine pre-percutaneous MV commissurotomy using multiplanar reconstruction in mid-esophageal apical long-axis view from LA prospective). By 2D transthoracic echo, patient group revealed significantly lower all LA function vs. control group including LA strain during reservoir (24 ± 6 vs. 43 ± 3, P < 0.001), LA strain during conduit (-11 ± 3 vs. -25 ± 2, P < 0.001), and during booster pump (-13 ± 4 vs. -18 ± 1, P < 0.001). EPAP was significantly higher in patient group (48 ± 7 vs. 27 ± 4 in control group). LV GLS was significantly lower in patient group (-16±2% vs. -23±2% in control group). All 3D LA volumes were significantly higher in patient group than control group including maximum LA volume (LAVmax) (76 ± 18 vs. 50 ± 5, P < 0.001), indexed LA volume (LAVi) (44.6 ± 10.1 vs. 28.7 ± 3.7, P < 0.001), LV minimum volume (LAVmin) (51 ± 15 vs. 30 ± 4, P < 0.001), and LA volume pre atrial contraction (LAVpre A) (63 ± 15 vs. 41 ± 6, P < 0.001). Also, there was significantly decreased LA strain using 3D speckle tracking echo in patient group including systolic deformation of LA (reservoir function) (23 ± 6 vs. 41 ± 3, P < 0.001) and diastolic deformation, early diastole (conduit function) (-10 ± 2 vs. -24 ± 2, P < 0.001), and late diastole (booster pump function) (-13 ± 4 vs. -18 ± 1, P < 0.001). All LA function markedly reduced in pure severe rheumatic MS. The reduction of LA mechanics is directly related to the degree of reduction of the stenotic MV area. LV GLS significantly reduced in severe MS and its reduction is directly related to the degree of reduction of the stenotic MV area and the LAVi by 3D echo.

Correlation between the level of C-reactive protein and the parameters of the functional status of the left atrium in patients with lymphoproliferative diseases against the background of chemotherapy

Aim. To assess the dynamics of functional changes in the left atrium (LA) in patients with lymphoproliferative diseases (LPD) before polychemotherapy (PCT), during treatment, after 6 courses of treatment, and the frequency of supraventricular arrhythmias (SVA) as well as the level of C-reactive protein. Material and methods. This is a prospective observational study of patients with confirmed diagnosis of lymphoma (n = 30; 57% men; median age 52 [34; 65] years old), who had no prior polychemotherapy. The comparison group included persons without lymphoma (n = 30; 49% men; median age 49 [36; 65] years old) comparable to the main group in terms of sex, age and risk factors for cardiovascular diseases. Patients with lymphoma underwent 24h-ECG monitoring and advanced transthoracic echocardiography with 2D speckle-tracking at baseline, and after 3 and 6 cycles (within 3 and 6 months) of anticancer treatment. Biomarkers of inflammation were measured. The results were compared to the data of the comparison group. Results. In lymphoma patients GLS LA, LA strain reservoir, LA strain conduit, and LA strain booster pump were found to be impaired at baseline but were comparable with these in matched controls. There was a significant decrease in GLS LA (LA strain reservoir 30% [26–41] vs 17% [15–31], p = 0.015) after 6 courses of PCT. In lymphoma patients before PCT, supraventricular tachycardia (SVT) was recorded significantly more often than in patients of the comparison group: 53% (n = 16) versus 20% (n = 6), (p = 0.02). The frequency of SVT was comparable in patients with LPD before and after 6 courses of chemotherapy: 53% (n = 16) vs 47% (n = 14) (p = 0 .7). Associations between the parameters of structural and functional changes in the LA and the incidence of SVA were not identified. A close correlation was found between the level of ESR, CRP and the parameters of the functional state of the LA. There was a significant relationship of the average strength between the ESR and the number of SVE in the analysis at all control points (rxy = 0.44, p &lt; 0.05). Conclusions. In lymphoma patients LA dysfunction occurs, which progressively worsens against the background of antitumor therapy, and is associated with the severity of systemic inflammation that may be a manifestation of the cardiotoxic effect of PCT, but additional studies are required.

Abnormal left atrial strain is associated with eventual diagnosis of atrial fibrillation in patients with embolic stroke of undetermined source

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with embolic stroke of undetermined source (ESUS) have no immediate attributable cause despite initial evaluation. Occult paroxysmal atrial fibrillation (pAF) diagnosed on prolonged electrocardiographic monitoring may be subsequently found in 20% of patients initially classified as ESUS [1]. Anatomic and functional alterations of left atrium (LA) are known to predict pAF in the general population [2]. Recent studies have suggested that LA dysfunction is linked to the risk of development of pAF in stroke patients and may precede LA enlargement [1]. LA strain analysis may be helpful to predict the development of pAF as it can detect subclinical functional impairment [2]. The aim of this study was to analyse whether LA strain can be a marker for the development of new-onset AF in patients with ESUS and sinus rhythm. Methods Our single-centre observational cohort study examined 157 patients hospitalised for ESUS in our tertiary hospital between October 2014 and October 2017 who underwent AF monitoring with an implantable loop recorder (ILR). These patients were followed up for occurrence of new-onset pAF and recurrence of ischaemic stroke. All patients underwent transthoracic echocardiography (TTE) during index hospitalisation as part of the workup for ESUS. Echocardiographic images were obtained and analysed post-hoc for two-dimensional (2D) speckle tracing deformation parameters. These LA strain parameters were analysed against the primary outcome of AF detection and secondary outcome of recurrent ischaemic stroke. Results A total of 157 ESUS patients, with a mean age of 61.0 (±11.6) years, were followed up for a median duration of 3.5 (interquartile range 3.29) years. ILR monitoring detected AF in 27 patients (17.2%). 27 patients developed recurrent ischaemic strokes. Of the 27 patients with newly diagnosed AF on ILR, 24 (88.9%) were commenced on oral anticoagulation; the remaining 3 patients were not on anticoagulation due to high bleeding risk and frailty. Patients who had newly diagnosed AF had more impaired left atrial reservoir strain (LASr; 23.5% ± 10.3%, P = 0.042) and left atrial conduit strain (LAScd; -10.5% ± 5.3%, P = 0.003) compared with patients who remained in sinus rhythm. Multivariable logistic regression analysis adjusting for age, sex, hypertension, hyperlipidaemia, diabetes mellitus and left ventricular ejection fraction (LVEF) showed that LAScd was associated with occult AF (adjusted odds ratio [aOR] = 1.110, 95% CI, 1.019-1.209, P = 0.017) and the composite outcome of AF and recurrent ischaemic stroke (OR = 1.069, 95% CI, 1.014-1.138, P = 0.038). Abnormal LAScd was significantly associated with occult AF even when stratified by normal LA volume index (LAVI) (OR = 2.672, 95% CI, 1.035-8.548, P = 0.048) and high LAVI (OR = 1.713, 95% CI, 1.023-2.869, P = 0.041). Conclusion Impaired left atrial strain was associated with occult AF detection in patients with ESUS undergoing ILR monitoring.

Left Atrial Velocity Vector Imaging Can Assess Early Diastolic Dysfunction in Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy

The function of left atrium (LA) is difficult to assess because of its ventricle-dependent, dynamic movement. The aim of this study was to assess LA function using velocity vector imaging (VVI) and compare LA function in patients with hypertrophic cardiomyopathy (HCMP) and left ventricular hypertrophy (LVH) with normal controls. Fourteen patients with HCMP (72% male, mean age of 52.6 ± 9.8), 15 hypertensive patients with LVH (88% male, mean age of 54.0 ± 15.3), and 10 age-matched controls (83% male, mean age of 50.0 ± 4.6) were prospectively studied. Echocardiographic images of the LA were analyzed with VVI, and strain rate (SR) was compared among the 3 groups. The e' velocity (7.7 ± 1.1; 5.1 ± 0.8; 4.5 ± 1.3 cm/sec, p = 0.013), E/e' (6.8 ± 1.6; 12.4 ± 3.3; 14.7 ± 4.2, p = 0.035), and late diastolic SR at mid LA (-1.65 ± 0.51; -0.97 ± 0.55; -0.82 ± 0.32, p = 0.002) were significantly different among the groups (normal; LVH; HCMP, respectively). The e' velocity, E/e', and late diastolic SR at mid LA were significantly different between normal and LVH (p = 0.001; 0.022; 0.018), whereas LA size was similar between normal and LVH (p = 0.592). The mean late diastolic peak SR of mid LA was significantly correlated with indices of diastolic function (E/e', e', and LA size). The SR is a useful tool for detailed evaluation of LA function, especially early dysfunction of LA in groups with normal LA size.

The association of left atrial mechanics with left ventricular morphology in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance study.

Hypertrophic cardiomyopathy (HCM) is related with structural and pathologic changes in the left atrium (LA) and left ventricle (LV). The aim of this study was to explore the association between LA mechanics and LV characteristics in patients with HCM using cardiac magnetic resonance feature tracking (CMR-FT). A total of 76 patients with HCM and 26 healthy controls were included in the study. The parameters including the extent of LV late gadolinium enhancement (LGE-%) and the LV early diastolic longitudinal strain rate (edLSR) were assessed for LV. LA conduit, booster, and reservoir functions were assessed by LA fractional volumes and strain analyses using CMR-FT. HCM patients were classified as HCM patients without LGE, with mild LGE-% (0% < LGE-% ł 10%), and prominent LGE-% (10% < LGE-%). HCM patients had worse LA functions compared with the controls (p < 0.05). The majority of LA functional indices were more impaired in HCM patients with regard to LGE. LA volumes were higher in HCM patients with prominent LGE-% compared with HCM patients with mild LGE-% (p < 0.05). However, only a minority of LA functional parameters differed between the 2 groups. LA strain parameters showed weak to modest correlations with LV LGE-% and LV edLSR. LV characteristics, to some extent, influence LA mechanics, but they might not be the only factor inducing LA dysfunction in patients with HCM.

Left Atrial Dysfunction in Children with Repaired Pulmonary Artery Atresia with Ventricular Septal Defect: A Cardiovascular Magnetic Resonance Imaging Study.

(1) Background: The left atrium (LA) is much more than a reservoir for left ventricular filling. The aim of this study was to assess the LA volume and function in patients with repaired pulmonary artery atresia with ventricular septal defect (rPA/VSD) using CMR. (2) Methods: 31 pediatric patients with rPA/VSD and 30 healthy controls were prospectively recruited. Left atrial ejection fraction (EF), strain and strain rate of three phases (reservoir, conduit, and pump) and left atrial volume were measured with cardiac function analysis software. (3) Results: Patients with rPA/VSD had decreased maximal volume index (p = 0.008). Compared to controls, LA reservoir strain and strain rate, conduit strain and strain rate, booster pump strain rate, total EF and passive EF were significantly lower (p = 0.001, p < 0.001, p = 0.001, p = 0.02, p = 0.03, p < 0.001, p < 0.001); the patients with preserved but lower RVEF(<50%) had lower reservoir strain, reservoir strain rate and pump strain rate (p = 0.01, p = 0.02, p = 0.04, respectively) than the patients with higher RVEF (≥50%). (4) Conclusions: In patients with rPA/VSD, LA function was altered when biventricular EF was preserved, which may provide an early indication of left ventricular diastolic dysfunction. CMR can detect LA dysfunction at an early stage, even before LA enlargement.

Prognostic implications of biventricular and left radial strain in heart failure

Abstract Background Chronic heart failure (CHF) is associated with the high ventricular filling pressures with subsequent negative impact on the left (LV) and right ventricular (RV), and left atrium (LA) mechanics, and pulmonary vasculature. All these could lead to poor long-term outcome. Purpose Assess the prognostic implications of LA, LV and RV mechanical dysfunction, and pulmonary hypertension, in CHF based on advanced echocardiographic technology. Methods A total of 2110 CHF patients were retrospectively reviewed and enrolled for the analyses. The 2D-Speckle tracking echocardiographic analysis was used to measure the peak LV, RV and LA longitudinal strain. The long-term outcomes were evaluated for all-cause CVS outcomes and recurrent hospitalization. Results For the 941eligible patients [mean age: 61±4; 62% male sex], 244 reached the combined endpoint. Population was divided into three groups based on the mean pulmonary artery systolic pressure (mPASP): Group 1, 25&amp;lt;mPASP≤40 mmHg; Group 2, 40&amp;lt;mPASP≤55 mmHg and Group 3, &amp;gt;mPASP 55 mmHg. Mean follow-up was 2.5±0.6 years. The higher mPASP was demonstrated in those with higher left atrial volume ndex (LAVI), NYHA ≥II class, pulmonary diseases, presence of at least moderate mitral and/or tricuspid regurgitation (TR) grades, significantly lower LVEF, lower strain values (LA, LV, RV), and tricuspid annular plane systolic excursion (TAPSE), p&amp;lt;0.001). High mPASP, lower LVEF and RV dysfunction were independent predictors of survival after multiple adjustments using different models. Conclusions Multiple factors are associated with poor outcomes in CHF; particularly the presence of RV dysfunction, severe PH and severely impaired, which would guide further manage of CHF and to consider other treatment options including device therapy or even transplantation. All these factors could strongly influence the risk stratification of patients with CHF Funding Acknowledgement Type of funding sources: None.

Left atrial dysfunction may precede left atrial enlargement and abnormal left ventricular longitudinal function: a cardiac MR feature tracking study

BackgroundThe role of the dysfunction of left atrium in the occurrence and development of cardiovascular disease has been gradually recognized. We aim to compare the impact on left atrial (LA) function between patients with hypertrophic cardiomyopathy (HCM) and hypertension (HTN) without LA enlargement using cardiovascular magnetic resonance feature tracking (CMR-FT), and if possible, explore the capability of LA function for providing clinical implication and predicting clinical adverse events in the early stage of cardiovascular disease.MethodsConsecutive 60 HCM patients and 60 HTN patients with normal LA size among 1413 patients who underwent CMR were retrospectively analyzed as well as 60 controls. Left atrial and ventricular functions were quantified by volumetric and CMR-FT derived strain analysis from long and short left ventricular view cines. The primary endpoint was a composite of all-cause death, stroke, new-onset or worsening heart failure to hospitalization, and paroxysmal or persistent atrial fibrillation.ResultsCompared to the controls, both HTN and HCM participants had impaired LA reservoir function (εs) and conduit function (εe) with the different stage of LA booster pump dysfunction (εa). LA strain was more sensitive than LV longitudinal strain (GLS) for evaluate primary endpoint (εs: 33.9% ± 7.5 vs. 41.2% ± 14.3, p = 0.02; εe: 13.6% ± 6.2 vs. 17.4% ± 10.4, p = 0.03; εa: 20.2% ± 6.0 vs. 23.7% ± 8.8, p = 0.07; GLS: -19.4% ± 6.4 vs. -20.0% ± 6.8, p = 0.70, respectively). After a mean follow-up of 6.8 years, 23 patients reached primary endpoint. Cox regression analyses indicated impaired LA reservoir and booster pump strain were associated with clinical outcomes in patients at the early stage of HTN and HCM (p < 0.05).ConclusionsCMR-FT-derived strain is a potential and robust tool in demonstrating impaired LA mechanics, quantifying LA dynamics and underlining the impacts on LA-LV coupling in patients with HTN and HCM without LA enlargement. The corresponding LA dysfunction is a promising metric to assess clinical implication and predict prognosis at the early stage, superior to GLS.

Cardiac Imaging for the Assessment of Left Atrial Mechanics Across Heart Failure Stages.

The left atrium (LA) is emerging as a key element in the pathophysiology of several cardiac diseases due to having an active role in contrasting heart failure (HF) progression. Its morphological and functional remodeling occurs progressively according to pressure or volume overload generated by the underlying disease, and its ability of adaptation contributes to avoid pulmonary circulation congestion and to postpone HF symptoms. Moreover, early signs of LA dysfunction can anticipate and predict the clinical course of HF diseases before the symptom onset which, particularly, also applies to patients with increased risk of HF with still normal cardiac structure (stage A HF). The study of LA mechanics (chamber morphology and function) is moving from a research interest to a clinical application thanks to a great clinical, prognostic, and pathophysiological significance. This process is promoted by the technological progress of cardiac imaging which increases the availability of easy-to-use tools for clinicians and HF specialists. Two-dimensional (2D) speckle tracking echocardiography and feature tracking cardiac magnetic resonance are becoming essential for daily practice. In this context, a deep understanding of LA mechanics, its prognostic significance, and the available approaches are essential to improve clinical practice. The present review will focus on LA mechanics, discussing atrial physiology and pathophysiology of main cardiac diseases across the HF stages with specific attention to the prognostic significance. Imaging techniques for LA mechanics assessment will be discussed with an overlook on the dynamic (under stress) evaluation of the chamber.

Morphological and secretory dysfunction of left atrium in Marfan syndrome

Abstract Introduction Marfan syndrome (MFS) is characterized by a mutation in the FBN1-gene which leads to a structural deficiency of the extracellular matrix component fibrillin-1 and a dysregulation of TGFβ. In recent years, cardiac remodeling with systolic and/or diastolic left ventricular dysfunction was shown in some MFS patients (Marfan Cardiomyopathy). Interestingly, in animal studies it has been shown that fibrillin-1 is abundantly present in atria and that TGFβ overexpression leads to atrial but not ventricular fibrosis (1, 2). However, the role of MFS for atrial remodeling and secretion (NT-proBNP) is unclear. Purpose To assess morphological and secretory function of the left atrium (LA) in patients with MFS and its relationship to left ventricular function. Methods We retrospectively analyzed echocardiographic and laboratory data in 307 Patients with MFS and in 147 healthy controls who had presented at our Marfan clinic between 23 February 2016 and 15 June 2020. At every visit, echocardiography had been carried out and NT-proBNP levels had been taken. A two-level mixed effects model was now performed to compare left atrial size between patients with MFS and controls. Results Left atrial size was significantly increased in patients with Marfan syndrome with and without aortic operation in medical history compared with controls (adjusted means: 18.4cm2 and 17.6cm2 vs. 15.5cm2 p&amp;lt;0.05). Body surface area (6.12, 95% CI: 4.26, 7.98 p&amp;lt;0.001), age (0.06, 95% CI: 0.02, 0.1 p&amp;lt;0.01), E/e' (0.3, 95% CI: 0.14, 0.46 p&amp;lt;0.001) and EF (−0.05, 95% CI: −0.10, −0.01 p=0.011) were significantly correlated with LA size. NT-proBNP was also increased, after logarithmic transformation, mean difference between unoperated patients with MFS and controls was 0.34 (95% CI: 0.11,0.57 p=0.004). Interestingly, NT-proBNP and LA size both were increased also in patients with normal left ventricular filling pressures, assessed by E/e' (see Figure 1). For increased LV filling pressures (E/e'&amp;gt;8), regression analyses revealed a more extensive dilatation of LA size in patients with MFS for further increase of E/e' compared to controls, although not significant for the latter. Haploinsufficiency mutations were associated with significant higher levels of NT-proBNP than dominant-negative (p=0.043) (see Figure 2), although this could not be shown for LA size. Atrial fibrillation (AF) tended to be more common in Marfan group (17/307 to 4/147, χ2 (1) = 1.79, p=0.181) but most patients with AF also had prior aortic operation. Conclusions Our data show that Marfan syndrome is associated with left atrial dilatation, accompanied by increased levels of NT-proBNP which seem to be independent of elevated left ventricular filling pressure. This supports the idea of a primary impairment of cardiac function. If this leads to an impaired clinical outcome, e.g. characterized by increased prevalence of AF and stroke, needs be investigated by further research. Funding Acknowledgement Type of funding sources: None.

Atrial Fibrillation (AF) and Ibrutinib, a Monocentric Experience: Should Cardiological Evaluation be a Guide in Clinical Practice?

IntroductionReported prevalence of AF in patients with chronic lymphocytic leukemia (CLL) on ibrutinib is approximately 5-10%. Management of AF in ibrutinib treated patients represents a multidisciplinary and challenging clinical need. Despite therapeutic advances, substantial morbidity and mortality still remain, and preventive or therapeutic strategies need to be implemented. Older age, male gender, arterial hypertension (AH) and valvular heart disease have recently been recognized as strong predictors of AF on ibrutinib. A clear relationship exists between an enlarged left atrium (LA), assessed by transthoracic echocardiography (TTE), and incidence of AF. LA dysfunction at ibrutinib start has been suggested as a predictor of AF: it helps identifying a selected cohort of patients who may benefit from strict follow-up and preventive strategies to reduce incidence of AF and associated complications. To date no prospective clinical trials have been conducted.AimTo analyse cardiovascular predictors and incidence of AF in a monocentric population of CLL patients on ibrutinib and in regular cardio-oncologic follow-up.MethodsFrom June 2014 to June 2017 we prospectively evaluated CLL patients requiring ibrutinib treatment at our Institution. Before starting therapy a full cardiovascular evaluation including accurate history, clinical examination and assessment of concomitant cardiovascular risk factors and cardioactive therapy were performed by an expert cardio-oncologist. All patients underwent non-invasive instrumental investigations performed by the same clinician: baseline electrocardiography (ECG) was used for rhythm documentation and TTE was focused on studying LA size and function. In a selected group of patients a 24 hours ECG monitoring was performed.ResultsFourty-three patients on ibrutinib were evaluated for a median of 12 months (range 1-37). Male/female ratio was 2.07 (M/F 29/14) and median age was 71 years (range 54-86). AF occurred in 7 patients (16.3%) after a median period of 6 months from the beginning of ibrutinib. Before starting therapy 30 patients (69.8%) had at least one cardiovascular risk factor, with 23 (53.5%) suffering from AH and 27 (62.8%) having more than one cardiovascular comorbidity. Twenty-three patients (53.5%) were regularly taking at least one cardioactive drug. We observed male gender and AH (p=0.009) to be significantly related to incidence of AF (p=0.04). One or more pre-existent cardiovascular comorbidity was found to be a strong predictive factor for AF (p=0.03). Concomitant cardioactive therapy and incidence of AF failed to show a significant correlation. Analysing TTE data, a strong predictive value of increased LA linear dimensions (p 0.02) and area (p 0.03) clearly emerged. Sixteen patients (37.2%) were evaluated through prolonged ECG-monitoring. We observed a trend to significance (p=0.07) of a higher maximal heart rate (HR) (109,5±0,7) reached in AF patients compared to those in stable sinus rhythm (73,35±30,6): higher HR, uncovering an increased sympathetic tone, is known to be a risk factor for AF. No significant correlation emerged between occurrence of AF and atrial conduction abnormalities recorded by baseline ECG.ConclusionsDue to the widespread use of ibrutinib in CLL population prompt recognition of AF high risk patients represents an emerging issue.As reported in literature, male sex and AH significantly correlate with AF development. LA enlargement represents a strong predictive factor for AF and TTE can reliably be used as a non-invasive exam to detect early signs of atrial dysfunction. In our cohort AF has occurred in a slightly higher percentage of patients treated with Ibrutinib than in literature. This finding, especially if validated in a larger CLL cohort, can suggest that silent, undetected AF is a common and a often underdiagnosed event in older patients with multiple risk factors. These initial results support a systematic cardiologic monitoring and AF screening program. Proper cardiological evaluation aims to identify patients at higher risk of AF. Educating patients to early recognize adverse events and behave accordingly to clinician's instructions allow to avoid unnecessary drug suspension. Comorbidity control and implementation of cardioactive therapy by an expert cardio-oncologist, preventing LA dilation and dysfunction, could be pursued as a means of reducing AF on ibrutinib. DisclosuresNo relevant conflicts of interest to declare.

Left atrial dysfunction and stiffness in pediatric and adult patients with Type 1 diabetes mellitus assessed with speckle tracking echocardiography.

Subclinical diastolic dysfunction in patients with Type 1 diabetes mellitus (T1DM) caused by myocardial injury due to diabetic cardiomyopathy leads to a high risk of death and heart failure. This myocardial injury extends not only to the left ventricle (LV) but also to the left atrium (LA). However, LA function in children and young adults with T1DM has not been extensively studied. Therefore, the aim of this study was to assess LA dysfunction in pediatric and adult patients with T1DM using LA strain analysis with echocardiography. Fifty-three patients (median age: 23 [range: 5-41] years) with T1DM. We divided the patients into three age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-41 years); 53 age- and sex-matched controls were divided into three corresponding groups (C1, C2, and C3). LA and LV functions were evaluated using echocardiography. LA reservoir strain was lower in the D2 and D3 groups than in the C2 and C3 groups (P = 0.001, P = 0.004, respectively). LA conduit strain was lower in the D2 group than in the C2 group (P = 0.002). LA stiffness was significantly greater in the D3 group than in the C3 group (P < 0.001). In patients with T1DM, LA phasic function decreased in adolescents and young adults, and LA stiffness increased in adult patients aged >30 years. LA phasic function and LA stiffness can be potentially used as early markers for diastolic dysfunction.

Left atrial reservoir strain in relation to metabolic and inflammatory biomarkers: a community-based study

Abstract Background The pathophysiological mechanisms that underlie progressive left atrium (LA) remodelling and dysfunction are only partially understood. Metabolic disturbances and chronic inflammation might mediate LA dysfunction. To date, population data investigating the contribution of these processes to LA reservoir dysfunction remain scarce. Purpose In a large population sample, we investigated the association between LA reservoir function and a panel of 38 metabolic and inflammatory biomarkers. Methods In 1236 community-dwelling individuals (mean age, 51.0 years; 51.5% women), we echocardiographically assessed LA reservoir strain (LARS) using 2D speckle-tracking analysis. LA reservoir dysfunction was defined as having LARS &amp;lt;23%. We applied partial least squares-discriminant analysis (PLS-DA) to identify biomarkers associated with LA dysfunction. We further explored the associations between LARS and selected biomarkers that were the most influential in PLS-DA, while adjusting for important clinical correlates such as age, sex, body mass index (BMI), heart rate, systolic blood pressure (BP) and antihypertensive treatment. We applied stepwise regression to identify the clinical features and circulating biomarkers most valuable for prediction of abnormal LARS. Results The three latent factors constructed from the panel of 38 biomarkers during PLS-DA explained 16.9% of the variation between the normal and the impaired LA function group. The PLS-DA model discriminated between normal and abnormal LA reservoir strain with 79% accuracy (P&amp;lt;0.0001). In PLS-DA, serum uric acid, serum insulin, γ-glutamyl transferase, interleukin-6, D-dimer and triglycerides were the top biomarkers responsible for class discrimination. On average, these top biomarkers were higher in the LA dysfunction group as compared to their normal counterparts (P&amp;lt;0.0001 for all). In multivariable-adjusted continuous analyses, LARS decreased significantly with the level of serum insulin, serum uric acid and γ-glutamyl transferase (P≤0.0035 for all). Of the clinical correlates and the top biomarkers selected in PLS-DA, stepwise regression models highlighted age, BMI, systolic BP, serum insulin, serum uric acid and interleukin-6 as the main predictors of an impaired LA reservoir function (see figure). Conjointly, these clinical and biochemical features identified LA reservoir dysfunction with an overall accuracy of 85%. Conclusions Circulating markers of insulin resistance, hyperuricemia and chronic inflammation were independently associated with impaired LA reservoir function. These markers may help to further unravel the pathophysiological processes behind LA maladaptation and improve the management of early LA dysfunction in the community. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders

Is insulin resistance play a role in left atrium dysfunction in young hypertensive patients?

Abstract Insulin resistance with normoglycemia could lead to subclinical inflammation, left atrium enlargement and ventricular systolic and diastolic dysfunction. The aim of our study was to analyzed associations between markers of insulin resistance and parameters of left atrium function in young hypertensive patients. Methods 965 young people were screened, among which 64 (6.6%) had high normal blood pressure and 57 (5.9%) had arterial hypertension. 121 patients with uncomplicated arterial hypertension grade 1–2 were included to the study (81% male, mean age 25.6 (7.3) years, 22 (18%) had obesity, 51 (42%) were smokers). All patients undergone clinical and laboratory evaluation, 24-h blood pressure monitoring, echocardiography. LA function were evaluated by 2D-speckle tracking echocardiography with left atrial reservoir strain (LASr), left atrial booster strain (LASb), left atrial conduit strain (LACs). Insulin level, serum glucose, was measured by using overnight fasting blood sampling between 7 am and 9 am. Insulin resistance was evaluated by HOMA-IR. Results Mean office systolic BP was 132 [122; 138]; diastolic BP – 70 [63; 76]. LAVI was 23 [19; 27] ml/m2. Mean insulin was 8.1 [5.4; 12.3] mIU/l, HOMA-IR – 1.9 [1.2; 2.8]. Correlations between LASr and body mass, waist circumference, insulin level, uric acid, HOMA-IR, E/e', LASb and insulin, HOMA-IR, uric acid, LASc and body mass, waist circumference, insulin level were revealed (p&amp;lt;0.05). Independent association LASc with BMI (B −0.22, p=0.02), LASb with insulin level (B −0.37, p=0.02), LASr with insulin (B −0.37, p=0.02) and with left ventricular (LV) global longitudinal strain (B −0.32, p=0.046) were confirmed in multiple stepwise regression model. Associations between endomyocardial LASb and insulin, HOMA-IR, endomyocardial LASr and body mass, waist circumference, insulin, uric acid, HOMA-IR, E/e', LASra and insulin and HOMA-IR, LASre with body mass, waist circumference, insulin, uric acid, HOMA-IR (p&amp;lt;0.05) were found during correlation analysis. Multiple stepwise regression showed independent associations endomyocardial LASb with HOMA-IR (B −0.44, p=0.005), endomyocardial LASr with HOMA-IR (B −0.46, p=0.003) and with LV global longitudinal strain (B −0.31, p=0.04), LASra with HOMA-IR (B −0.46, p=0.008), LASre with body mass (B −0.48, p=0.036) and with insulin (B −0.38, p=0.001). Conclusion Left atrium reservoir function is load dependent and influenced by LV function. For subclinical left atrium remodeling assessment booster function should be analized along with reservoir function. In young hypertensive patients insulin level were independently associated with left atrial dysfunction. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Project 5-100