Atrial Ejection Fraction Research Articles

Longitudinal Worsening of Left and Right Sided Cardiac Function in Patients with Sickle Cell Disease

Rationale: Sickle cell disease (SCD) is a genetic hemoglobinopathy characterized by hypercoagulability and accelerated mortality. Venous thromboembolism (VTE) occurs in 11-12% of SCD patients by age of 40 and increases mortality risk two to three-fold. Transthoracic echocardiography (TTE) can identify mortality risk factors in SCD including an elevated tricuspid regurgitant jet velocity (TRV) and diastolic dysfunction. We sought to characterize longitudinal changes in left and right sided cardiac function and to identify the impact of VTE in this process. Methods: We conducted a retrospective review of 402 consecutive SCD adults, 18 years of age and older, treated at our institution between 2003 and 2021. Deep venous thrombosis and/or pulmonary embolism with confirmatory diagnostic imaging defined VTE. Demographics, clinical history, laboratory data, and diagnostic evaluation were abstracted from the medical record. For echocardiographic data, clinical echocardiograms were individually re-analyzed with extensive coding of left ventricular (LV) and right ventricular (RV) systolic and diastolic function. Data were recorded at time of first contact or prior to VTE if applicable and were repeated at five years post-VTE. In the non-VTE group, baseline and five-year longitudinal data were obtained. Results: Within our cohort, 62% were HbSS/HbSβ 0, 56% were female, and 19% had a prior VTE. Prior history of acute chest syndrome, stroke, surgical splenectomy, and avascular necrosis was more common in the VTE group (p<0.01 for each comparison). Mortality was significantly higher in the VTE group compared to the non-VTE group (13% v 6%, p=0.04). In our cohort, 146 patients had initial and 5-year follow-up echocardiography (107/329 of non-VTE group, 39/75 of VTE group). Longitudinally, there were significant declines in both medial e ‘ and lateral e’ velocity and the E/A ratio, reflective of worsening left ventricular diastolic dysfunction. Right-sided cardiac function also worsened with a significantly increased TRV and right ventricular base dimension in follow-up echocardiograms. Of note, the baseline TRV was higher in the VTE group compared to the non-VTE group. In the VTE group, E/A ratio significantly decreased and RV base dimension significantly increased on follow-up study. In the non-VTE group, significant increases in TRV and RV base dimension were observed along decreases in left atrial ejection fraction, medial and lateral e', and E/A ratio on follow-up study (Table 1). Conclusions: Patients with SCD and VTE have increased mortality compared to those without VTE. Echocardiography demonstrates longitudinal worsening of left ventricular diastolic and right-sided cardiac function. These changes were more pronounced in the non-VTE group, and the lack of changes in the VTE group may reflect missing data. Our findings need to be confirmed prospectively but suggest the importance of a deeper evaluation of echocardiography to better understand the progression of SCD related cardiac dysfunction and pulmonary hypertension.

Left atrial appendage angiography for stroke risk prediction in patients with atrial fibrillation.

The current risk stratification schemes for stroke in patients with atrial fibrillation (AF) are insufficient for an accurate assessment of stroke risk. This study evaluates the association between the mechanical function of the left atrial appendage (LAA), as assessed by angiography, and the risk of stroke. We conducted a cross-sectional study to assess the mechanical function of the LAA by measuring the left atrial appendage ejection fraction (LAAEF) and grading the contrast retention (CR) using angiography. A total of 746 patients referred for a left atrial appendage occlusion (LAAO) procedure with (n=151; stroke group) or without (n=595; control group) a history of stroke were included in the analysis. LAAEF was significantly lower (14% [9-19] vs 20% [12-33]; p<0.001) and grade 3 CR was more common (66.9% vs 33.9%; p<0.001) in patients with a history of stroke. Multivariable analysis showed that CR was independently associated with stroke in patients with AF (grade 2 vs grade 1=7.29; 95% confidence interval [CI]: 2.84-21.65; p<0.001; grade 3 vs grade 1=16.45; 95% CI: 6.16-51.02; p<0.001). The receiver operating characteristics curve demonstrated that CR identified patients with stroke more accurately than the CHA2D-VASc score (C-statistic 0.712 vs 0.512; p<0.001), and the combination of CR and the CHA2DS2-VASc score provided the best performance (C-statistic 0.871 vs 0.829 [CHA2DS2-VASc score alone]; p=0.048) Conclusions: Impaired mechanical function of the LAA, indicated by a low LAAEF and CR, is associated with a history of stroke in patients with AF. Assessment of CR using LAA angiography helps improve the stratification scheme for stroke risk prediction.

PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation.

Atrial fibrillation (AF)-the most common sustained cardiac arrhythmia-increases thromboembolic stroke risk 5-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C (protein phosphatase 1 regulatory subunit 12C)-the PP1 (protein phosphatase 1) regulatory subunit targeting MLC2a (atrial myosin light chain 2)-causes hypophosphorylation of MLC2a and results in atrial hypocontractility. Right atrial appendage tissues were isolated from human patients with AF versus sinus rhythm controls. Western blots, coimmunoprecipitation, and phosphorylation studies were performed to examine how the PP1c (PP1 catalytic subunit)-PPP1R12C interaction causes MLC2a dephosphorylation. In vitro studies of pharmacological MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with electrophysiology studies. In human patients with AF, PPP1R12C expression was increased 2-fold versus sinus rhythm controls (P=2.0×10-2; n=12 and 12 in each group) with >40% reduction in MLC2a phosphorylation (P=1.4×10-6; n=12 and 12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF (P=2.9×10-2 and 6.7×10-3, respectively; n=8 and 8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a and dephosphorylation of MLC2a. Mice treated with lentiviral PPP1R12C vector demonstrated a 150% increase in left atrial size versus controls (P=5.0×10-6; n=12, 8, and 12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in mice treated with lentiviral PPP1R12C vector was significantly higher than in controls (P=1.8×10-2 and 4.1×10-2, respectively; n=6, 6, and 5). Patients with AF exhibit increased levels of PPP1R12C protein compared with controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key determinant of atrial contractility in AF.

Association between subclinical atherosclerosis and cardiac structure and function-results from the UK Biobank Study.

Heart failure (HF) is a major health problem and early diagnosis is important. Atherosclerosis is the main cause of HF and carotid intima-media thickness (IMT) is a recognized early measure of atherosclerosis. This study aimed to investigate whether increased carotid IMT is associated with changes in cardiac structure and function in middle-aged participants of the UK Biobank Study without overt cardiovascular disease. Participants of the UK Biobank who underwent CMR and carotid ultrasound examinations were included in this study. Patients with heart failure, angina, atrial fibrillation, and history of myocardial infarction or stroke were excluded. We used multivariable linear regression models adjusted for age, sex, physical activity, body mass index, body surface area, hypertension, diabetes, smoking, ethnicity, socioeconomic status, alcohol intake, and laboratory parameters. In total, 4301 individuals (61.6 ± 7.5 years, 45.9% male) were included. Multivariable linear regression analyses showed that increasing quartiles of IMT was associated with increased left and right ventricular (LV and RV) and left atrial volumes and greater LV mass. Moreover, increased IMT was related to lower LV end-systolic circumferential strain, torsion, and both left and right atrial ejection fractions (all P < 0.05). Increased IMT showed an independent association over traditional risk factors with enlargement of all four cardiac chambers, decreased function in both atria, greater LV mass, and subclinical LV dysfunction. There may be additional risk stratification that can be derived from the IMT to identify those most likely to have early cardiac structural/functional changes.

Abstract EC.02: Myosin Light Chain Dephosphorylation By Ppp1r12c Promotes Atria Hypocontractility In Atrial Fibrillation

Background: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, increases thromboembolic stroke risk five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C, the PP1 regulatory subunit targeting atrial myosin light chain 2 (MLC2a), causes hypophosphorylation of MLC2a and results in atrial hypocontractility. Methods: Right atrial appendage tissues were isolated from human AF patients versus sinus rhythm (SR) controls. Western blots, co-immunoprecipitation, and phosphorylation studies were performed to examine how the PP1c-PPP1R12C interaction causes MLC2a de-phosphorylation. In vitro studies of pharmacologic MRCK inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with EP studies. Results: In human patients with AF, PPP1R12C expression was increased two-fold versus SR controls with &gt; 40% reduction in MLC2a phosphorylation. 12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF. In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Lenti-12C mice demonstrated a 150% increase in LA size versus controls, with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in Lenti-12C mice was significantly higher than controls. Conclusions: AF patients exhibit increased levels of PPP1R12C protein compared to controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key regulator of atrial contractility in AF.

The Relationship between Hyperuricemia and Echocardiographic Parameters in Patients with Chronic Atrial Fibrillation.

Purpose Uric acid serves as a marker for cardiovascular risk and is often linked to inflammation and oxidative stress. There is evidence suggesting an association between uric acid and atrial fibrillation (AF), including its severity and occurrence of crises, as well as its involvement in cardiovascular mechanisms. The objective of this study was to assess the correlation between hyperuricemia and echocardiographic features in patients with chronic AF lasting for more than 5 years. Methods This case-control study involved 107 patients diagnosed with chronic non-valvular AF. Uric acid levels were measured in all patients, and they were divided into two groups: the first group consisted of 66 patients with hyperuricemia (>7.2 mg/dL), while the second group included 41 patients with normal uric acid levels. Echocardiography (TTE) was performed to evaluate each patient. Various clinical and echocardiographic parameters, such as left ventricle telediastolic (LVTDD) and telesystolic (LVTSD) diameters, left atrial diameter (LAD), aortic diameter (AoD), ejection fraction (EF), and pulmonary artery pressure (PAP), were analyzed. Results Binary logistic regression analysis revealed a statistically significant relationship between uric acid levels (>7.2 mg/dL) and LAD. For each unit increase in LAD, the probability of having hyperuricemia increased by 9% [odds ratio (OD): 0.91, 95% confidence interval (CI): 0.84-0.99]. A significant relationship was found between uric acid levels (>8 mg/dL) and LVESD (p = 0.045) as well as PAP (p = 0.006). For every unit increase in LVESD, the likelihood of having uric acid levels greater than 8 mg/dL increased by 22% [OD: 0.82, 95% CI: 0.67-0.99, b = -0.2]. Likewise, for each unit increase in PAP, the probability of having uric acid levels greater than 8 mg/dL was 9.4% [OD: 0.91, 95% CI: 0.86-0.97, b = -0.09]. Conclusions This study demonstrates that hyperuricemia has a significant relationship with the development of atrial remodeling, with an important association observed between hyperuricemia and an increase in left atrial diameter. Hyperuricemia is also correlated with an enlargement of the left ventricle end-systolic diameter and pulmonary artery pressure, showing a possible influence that hyperuricemia might have also left ventricle morphology and right ventricle function.

Left atrial function as a determinant of symptoms in patients with severe degenerative mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Background Understanding the pathophisiology of symptoms onset in degenerative mitral regurgitation may be helpful in the management of asymptomatic patients. Left atrium (LA) is far from simply being a passive connection chamber between mitral valve and pulmonary circulation, and the role of left atrial function as a predictor of symptoms onset has not yet been evaluated. The increase in atrial pressure that causes elevation of pulmonary capillary pressures and the onset of dyspnoea may be driven by the reduction of left atrial compliance, which can be assessed by peak atrial longitudinal strain (PALS) derived from speckle tracking echocardiography. Aim To assess the role of left atrial function as a determinant of symptoms in patients with severe degenerative MR. Methods We analysed retrospectively all patients affected by severe degenerative MR evaluated for cardiac surgery between May 2019 and July 2022 at IRCCS San Raffaele Hospital. The cohort was divided in symptomatic (NYHA &amp;gt;I) and asymptomatic (NYHA =I) patients. A comprehensive assessment of LA function was performed including pulmonary venous blood flow, LA ejection fraction, LA fractional atrial change, and PALS. Patients with atrial fibrillation during echocardiographic evaluation, left ventricular disfunction and more than mild left heart valvulopathy associated with MR were excluded. Results The final study population consisted of 408 patients. The grade of MR, assessed by multiparametric approach, was not different between the two groups. Age, history of coronary artery disease, dyslipidaemia, hypertension and history of atrial fibrillation were found to be predictive on symptomatology. Fractional area change (OR: 0.89; CI:0.87–0.91, p &amp;lt;0.001), atrial ejection fraction (OR: 0.92, CI= 0.90–0.94, p &amp;lt;0.001), atrial volume(OR: 1.04, CI: 1.02–1.05, p&amp;lt;0.001), pulmonary artery systolic pressure(OR:1.09, CI:1.06–1.13, p&amp;lt;0.001) and longitudinal atrial strain (OR:0.88, CI:0.85–0.90, p&amp;lt;0.001) but not EROA ( OR:1.06, CI: 0.63–2.30, p = 0.8) were found to be predictive. On multivariate logistic regression, only indexed biplane LA volume (OR: 1.02, CI 1.00–1.07, p = 0.035) and PALS (OR: 1.02, CI: 0.87–0.94, p&amp;lt;0.001) were found to be predictive. The best PALS threshold to identify symptomatic patients was 22% (OR: 3.3, SE 67%, SP 87%). Conclusions LA function is a determinant of symptoms in severe degenerative MR. The reduction of PALS appears to be a predictor of symptoms and a value of PALS &amp;lt; 22% identified symptomatic patients with 85% specificity and 67% sensitivity.

Determinants and prognosis of aortic valve calcification in conjunction with carotid atherosclerosis and left ventricular function

Abstract Funding Acknowledgements Type of funding sources: None. Background Aortic valve (AV) sclerosis is known as a progressive atherosclerotic disease causing aortic stenosis (AS). However, its contributors and prognostic value in patients without overt AS have not been well investigated. Purpose In this study, we sought to evaluate its determinants and prognostic value in conjunction with carotid atherosclerosis and left ventricular (LV) function. Methods Consecutive 4,689 patients who underwent both carotid ultrasound and echocardiography were followed during 3.6 ± 1.3 years after exclusion of patients with bicuspid aortic valve (n=12), rheumatic heart disease (n=7), overt AS (n=62) and AV replacement status (n=10). AV sclerosis was classified as pure AV sclerosis and AV sclerocalcification according to cusp thickening and presence of hyper-echogenicity in any cusps. Results Their mean age was 61.1±11.7 years and 1,836 (39%) were women. Of them 2,003 (43%) had pure AV sclerosis and 523 (11%) had AV sclerocalcification. Presence of AV sclerocalcification was independently correlated with age, presence and degree of carotid plaques, ventricular septal thickness, high density lipoprotein level and presence of atrial fibrillation. Presence of AV sclerocalcification was significantly related with composite cardiovascular events (all CVE, unstable angina, acute myocardial infarction and all cause death; log rank p = 0.011) and future heart failure (HF) admission (p&amp;lt;0.001) but not with pure AV sclerosis. In multivariate analysis, presence of carotid plaques was most strongly associated with all CVE, however when adding AV sclerocalcification on carotid plaques, it added the significant prognostic values (p = 0.015). Regarding future HF admission, the significance was attenuated after introducing left atrial volume index and LV ejection fraction. Conclusions AV sclerocalcification has additive prognostic value on carotid plaque for future atherosclerotic events. Although, AV sclerocalcification was related to future HF admission it was mainly mediated by concomitant LV dysfunction, suggesting a surrogate marker rather than independent risk factor.

Routine 4D Cardiac Computed Tomography to Identify Concomitant Transthyretin Amyloid Cardiomyopathy in TAVI candidates with Severe Aortic Stenosis

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Bangerter-Rhyner Foundation, Pfizer, GAMBIT foundation. Background Transthyretin amyloid cardiomyopathy (ATTR-CM) may coexist in patients with severe aortic stenosis (AS) considered for transcatheter aortic valve implantation (TAVI). The diagnosis of ATTR-CM by 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD)-scintigraphy is costly, whereas endomyocardial biopsy is associated with relevant procedural risks and sampling error. Objectives To evaluate whether ATTR-CM may be diagnosed by routine 4D cardiac computed tomography (4DCCT). Methods In a prospective screening study for ATTR-CM, the diagnostic performance of 4DCCT-based left- (LV), right ventricular (RV) and left atrial (LA) dimensions, ejection fraction (EF) and myocardial strain was evaluated against DPD-scintigraphy to identify ATTR-CM. Diagnostic predictors and a newly developed 4DCCT-score were validated by internal bootstrapping. Results Among 263 patients considered for TAVI (57% males,age 83±4.6 years) undergoing 4DCCT, DPD-scintigraphy (Perugini grade 2–3) confirmed co-existing ATTR-CM in 27 (10.3%) patients. Patients with ATTR-CM had impaired 4DCCT-based LVEF, LV global longitudinal strain (GLS), and LA-GLS. LV mass index, LV-GLS, LA-GLS and relative apical longitudinal strain (ratio of apical to basal/midventricular strain), each predicted the presence of ATTR-CM with an area under the curve (AUC) of &amp;gt;0.7. Implementing these parameters with cutoff-values of ≥81g/m2, ≥-14.9%, &amp;lt;11.5% and ≥1.7 in an unweighted score yielded high prognostic accuracy (AUC=0.89; 95%CI:0.81–0.94;p&amp;lt;0.001), robust to internal bootstrapping validation (AUC=0.88;95%CI:0.82–0.94). If two criteria were fulfilled, sensitivity and specificity to detect ATTR-CM were 96.3 and 58.9%, respectively. Conclusions Clinically indicated, routine 4DCCT in patients considered for TAVI provides high diagnostic yield to detect concomitant ATTR-CM, by assessing LV- and LA-GLS, LV relative apical longitudinal strain and LV mass index.

Left Atrial Function Assessment By Speckle Tracking Echocardiography In Low-Risk Atrial Fibrillation Patients.

To compare the left atrial function utilising speckle tracking echocardiography in patients with low-risk and high-risk non-valvular atrial fibrillation. The descriptive, cross-sectional study was conducted at the cardiology department of Kafrelsheikh University Hospital, Egypt, from January 2021 to January 2022, and comprised low-risk atrial fibrillatin participants in group I, high-risk atrial fibrillatin patients in group II, and healthy controls in group III. After detailed medical history, the subjects underwent 12-lead electrocardigram, and echocardiographic assessment, including two dimensional, M-mode, tissue doppler, and speckle tracking of the left atrium. The association of left atrial strain with Congestive heart failure, hypertension, age ≥75 (doubled), diabetes,stroke (doubled), vascular disease sex category (female)score was explored. Data was analysed using SPSS 28. Of the 90 subjects, there were 30(33.3%) in each of the 3 groups. The mean age among the groups was significantly different among the groups (p=0.014). Left atrial ejection fraction and left atrial strain had an overall significant difference among the groups(p<0.001). Congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease sex category (female)score was negatively correlated with Left atrial ejection fraction and (p<0.001) and left atrial strain (p<0.001). In individuals with atrial fibrillatin, there was a significant decrease in left atrial strain and left atrial function. The use of speckle tracking echocardiography allowed for a more detailed analysis of left atrial mechanics. The correlation of left atrialstrain and left atrial ejection fraction with Congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease sex category (female) score was significantly negative.

Sex-Specific Impairment of Cardiac Functional Reserve in HFpEF: Insights From the HFpEF Stress Trial

BackgroundHeart failure with preserved ejection fraction (HFpEF) has been observed to have a twice as high prevalence in women compared to men with similar predisposing risk factors between both sexes. ObjectivesThis study aimed to identify sex-specific pathophysiological features in HFpEF using rest and exercise stress right heart catheterization (RHC), echocardiography and cardiovascular magnetic resonance imaging (CMR). MethodsSeventy-five patients with exertional dyspnea, preserved ejection fraction (EF) (≥50%), and signs of diastolic dysfunction on echocardiography were prospectively recruited in the HFpEF Stress Trial. Patients underwent RHC, echocardiography and CMR at rest and during exercise stress. Patients were diagnosed with HFpEF and noncardiac dyspnea according to RHC measurements. ResultsAfter exclusion, the final study cohort comprised 68 patients (females n = 44, males n = 24) with a mean age of 66.9 ± 9.7 years. Compared to men, women with HFpEF revealed lower right ventricular stroke volumes during exercise stress (females 38.1 vs males 50.4 mL/m2 BSA; P = 0.011). This was accompanied by a decreasing left atrial EF in women but not men comparing resting to exercise conditions (females −2.7% vs males 2.5%, P = 0.020) and impaired left ventricular filling (females 35.5 vs males 44.2 mL/m2 BSA, P = 0.017) in women with HFpEF during exercise stress. These sex-specific differences were not present in noncardiac dyspnea. ConclusionsWomen with HFpEF demonstrate sex-specific functional alterations of right ventricular, left atrial, and left ventricular function during exercise stress. This unique pathophysiology represents a sex-specific diagnostic target, which may allow early identification of women with HFpEF for future individualized therapeutic approaches.

Aortic Stiffness and Cardiac Modification After Open or Endovascular Aortic Treatment: Preliminary Results of a Single-Center Prospective Cohort Study

Increased aortic stiffness (AoS), is considered an independent marker of cardiovascular mortality and morbidity. Aortic endovascular treatment correlates to a worsening of AoS, indirectly evaluated with pulse wave velocity (PWV). This could lead to changes in cardiac geometry and efficiency over time. The aim of this study is to evaluate possible changes in AoS with consequent alterations in cardiac function after endovascular (ER) or open (OR) repair, also analyzing different endograft fabric. Patients who were candidate for elective ER or OR for different abdominal aortic disease were enrolled. PWV was measured during the preoperative period and after 1 year. Doppler echocardiography was performed before surgery and after 1 year evaluating arterial (Ea) and ventricular (Ees) elastance and their coupling (Ea/Ees), left ventricular left atrial volume index and left atrial volume index, ejection fraction, and ratio of early ventricular filling to atrial systole (E/A). Furthermore, systolic and diastolic blood pressure and exercise tolerance by the Specific Activity Scale score were assessed preoperatively and after one-year. All data were compared between ER and OR groups and between endo-PTFE and endo-Polyester group. Sixty patients have been enrolled in the 2-year period from 2019 to 2021 (19 OR and 41 ER). Both groups were homogeneous considering cardiovascular risk factors, except for age, which was lower for the OS group (67.2 ± 7.2 vs 75.4 ± 6.4 years; P < .001). Fifty-one patients completed the follow-up (13 OR, 38 ER). PWV increased in both groups, significantly in ER (+2.9 m/second; P = .016). Systolic blood pressure grew in both ER (+20.2 mm Hg; P < .001) and OR groups (+18.4 mm Hg; P = .005). Diastolic blood pressure grew in ER group (+5.2 mm Hg; P = .009) Ea increased +0.3 mm Hg/mL/m2 in both ER and OR groups (P = .026; P = .020), without significant changes in Ea/Ees coupling. E/A ratio decreased (−0.1; P < .001) in the ER group. No significant changes in left ventricular left atrial volume index, left atrial volume index and ejection fraction were recorded (Table I). In ER group, the Specific Activity Scale score got worse (+0.3; P = .004) and three cardiac events were recorded. Considering the subanalysis endo-PTFE vs endo-Polyester, PWV (+3.8 m/second; P = .023) and Ea (+0.4 mm Hg/mL/m2; P = .008) increased significantly in endo-Polyester group only (Table II). AoS increases after ER, mostly in patients with a polyester-covered device. Furthermore, the reversal of E/A ratio means an initial alteration in ventricular diastole, not related to significant mid-term changes in cardiac geometry. These changes could lead to diastolic disfunction with an increased risk of cardiovascular events over time. Further investigation is needed to validate our results.Table IPulse wave velocity (PWV), pressures and echocardiographic data after 1 year of follow-up in the open repair (OR) and endovascular repair (ER) groupsCharacteristicsOR (n = 13)P < .05ER (n = 38)P < .05Preoperative1 YearPreoperative1 YearPWV (m/second)11.6 ± 5.215.5 ± 8.1.05712.7 ± 3.615.6 ± 6.3.016SBP (mm Hg)132.9 ± 22.8151.3 ± 15.9.005134.7 ± 15.6154.9 ± 16.9<.001DBP (mm Hg)78.2 ± 8.481.9 ± 8.5.41573.9 ± 9.979.1 ± 8.4.009LVVi (mL/m2)50.3 ± 1257 ± 15.2.35948.1 ± 17.350.9 ± 16.2.093LAVi (mL/m2)31.5 ± 8.334.5 ± 13.6.89831.9 ± 6.634.9 ± 11.6.378EF (%)60 ± 5.758 ± 6.8.21559.4 ± 6.358.8 ± 6.1.604E/A ratio0.8 ± 0.31 ± 0.5.2500.8 ± 0.20.7 ± 0.2<.001Ea (mm Hg/mL/m2)1.4 ± 0.31.7 ± 0.4.0201.5 ± 0.51.8 ± 0.5.026Ees (mm Hg/mL/m2)1.6 ± 0.81.9 ± 0.5.1481.6 ± 0.61.7 ± 0.6.188Ea/Ees1 ± 0.30.9 ± 0.2.5781 ± 0.31.1 ± 0.3.740DBP, Diastolic blood pressure; Ea, arterial elastance; E/A, early ventricular filling to atrial systole ratio; Ees, ventricular end-systolic elastance; EF, ejection fraction; LAVi, left atrial volume index; LVVi, left ventricular volume index; SBP, systolic blood pressure.All data are reported as mean ± standard deviation. Open table in a new tab Table IIPulse wave velocity (PWV), pressures and echocardiographic data after 1 year of follow-up in endo-PTFE and endo-Polyester group.CharacteristicsEndo-PTFE (n = 15)P < .05Endo-Polyester (n = 23)P < .05Preoperative1 YearPreoperative1 YearPWV (m/second)11.7 ± 3.114 ± 4.6.09112.9 ± 3.116.7 ± 7.1.023SBP (mm Hg)128.7 ± 16.7157.3 ± 19.5<.001138.7 ± 13.9153.3 ± 15.1<.001DBP (mm Hg)68.7 ± 8.179 ± 7.1.00277.3 ± 9.479.1 ± 9.3.356LVVi (mL/m2)44.9 ± 9.647.7 ± 9.2.18450.2 ± 20.753 ± 19.4.330LAVi (mL/m2)32.8 ± 6.736.5 ± 13.2.31331.3 ± 6.833.9 ± 10.7.685EF (%)59.2 ± 4.158.9 ± 3.7159.5 ± 7.558.8 ± 7.2.557E/A ratio0.9 ± 0.30.7 ± 0.2.0160.8 ± 0.20.7 ± 0.2.001Ea (mm Hg/mL/m2)1.7 ± 0.71.7 ± 0.5.6071.4 ± 0.31.8 ± 0.5.008Ees (mm Hg/mL/m2)1.6 ± 0.71.8 ± 0.7.1761.6 ± 0.71.7 ± 0.6.637Ea/Ees1.1 ± 0.31 ± 0.3.5701 ± 0.31.1 ± 0.3.391DBP, Diastolic blood pressure; Ea, arterial elastance; E/A, early ventricular filling to atrial systole ratio; Ees, ventricular end-systolic elastance; EF, ejection fraction; LAVi, left atrial volume index; LVVi, left ventricular volume index; SBP, systolic blood pressure.All data are reported as mean ± standard deviation. 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Preclinical safety and biodistribution assessment of Ad-KCNH2-G628S administered via atrial painting in New Zealand white rabbits.

Post-operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Despite implementation of several pharmacological strategies, incidence of POAF remains at approximately 30%. An adenovirus vector encoding KCNH2-G628S has proven efficacious in a porcine model of AF. In this preclinical study, 1.5 × 1010 or 1.5 × 1012 Ad-KCNH2-G628S vector particles (vp) were applied to the atrial epicardium or 1.5 × 1012 vp were applied to the whole epicardial surface of New Zealand White rabbits. Saline and vector vehicle served as procedure controls. Animals were followed for up to 42 days. Vector genomes persisted in the atria up to 42 days, with no distribution to extra-thoracic organs. There were no adverse effects attributable to test article on standard toxicological endpoints or on blood pressure, left atrial or ventricular ejection fractions, electrocardiographic parameters, or serum IL-6 or troponin concentrations. Mononuclear infiltration of the myocardium of the atrial free walls of low-dose, but not high-dose animals was observed at 7 and 21 days, but these changes did not persist or affect cardiac function. After scaling for heart size, results indicate the test article is safe at doses up to 25 times the maximum proposed for the human clinical trial.

Analysis of bi-atrial function using CMR feature tracking and long-axis shortening approaches in patients with diastolic dysfunction and atrial fibrillation.

Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.

PO-01-095 REGIONAL DIFFERENCES IN ATRIAL FIBER STRAINS IN HEART FAILURE PATIENTS WITH AND WITHOUT ATRIAL FIBRILLATION

Left atrial (LA) strain is inhibited by atrial fibrosis, which is a hallmark of atrial fibrillation (AF). Retrospective gated computed tomography (CT) imaging with feature tracking (FT) can measure three-dimensional (3D) local LA strain. Atrial myocardial fiber directions may play an important role in preferred deformation, and therefore atrial fiber strains should be considered. Using the average endocardial fiber architecture from seven hearts imaged ex vivo with high resolution diffusion-tensor magnetic resonance imaging (DT-MRI), the endocardial fiber strain can be measured. To investigate regional and global differences in atrial endocardial fiber strains between heart failure (HF) patients with and without AF. 30 HF patients underwent 10-frame gated CT imaging, and FT was used to measure local endocardial fiber strain (Fig. A). The LA body was classified into five regions using Universal Atrial Coordinates (Fig. B). Global and regional strains were reported as the mean strain over the entire LA body surface and within each region, respectively. The fiber strain range over the cardiac cycle was used to stratify between HF patients with and without AF. The left ventricular ejection fraction (LVEF) and left atrial ejection fraction (LAEF) were calculated from the gated CT images. HF patients with AF had smaller global fiber strain ranges than those without AF (5.9 ± 3.7 % vs 14.2 ± 8.9 %, p = 0.011) (Fig. C). All regions had higher strain ranges in HF patients without AF and the anterior wall exhibited the most significant difference between groups (7.8 ± 4.1 vs 17.9 ± 10.6, p = 0.009). ROC analysis using global strain range to stratify between patient groups gave an AUC of 0.853 (Fig. D). The anterior wall was the region with the highest AUC of 0.842. LVEF was similar between patient groups (p=0.682), however LAEF differed (p=0.002) (Fig. E). Patients with AF had decreased fiber strain ranges globally and regionally compared to those without AF. Strain range in the anterior wall most significantly decreased in the presence of AF, which may suggest a regionally higher fibrosis burden. The LVEF was similar between HF patients with and without AF, however the LAEF differed, which suggests strain differences were driven by LA dysfunction.

PO-02-192 NEW ONSET, RECURRENCE AND PROGRESSION OF ATRIAL FIBRILLATION AFTER CARDIAC SURGERY DURING 2.5 YEARS OF CONTINUOUS RHYTHM MONITORING

Atrial fibrillation (AF) in the early postoperative phase (POAF) is a frequent complication after cardiac surgery which is also associated with late AF-recurrences. However, it is unknown how POAF-burden (percentage of time in AF) progresses in the time following surgery. Recent studies suggested that AF-burden is associated with increased risk of stroke and therefore identifying factors associated with a higher POAF-burden is desirable. To investigate POAF-burden progression patterns and factors associated with increased POAF-burden after cardiac surgery during 2.5 years of continuous rhythm monitoring. Patients with and without history of AF undergoing cardiac surgery were included. Preoperatively, all patients underwent transthoracic echocardiography, electrocardiography, and blood biomarker analysis. Continuous rhythm monitoring was performed over a period of 2.5 years with an implantable loop recorder. POAF-burden progression was calculated as percentage of time in AF for different time intervals (0-3, 3-12, and 12-30 months). Classification of burden was performed based on the cut-off values for tertiles. In addition, AF-characteristics such as episode duration and ventricular rate were analyzed as potential surrogate markers of POAF-burden. The study population consisted of 98 patients which completed 2.5 years of rhythm FU. Highest POAF-burden was observed in the first 3 postoperative months with a significant reduction between 3-12 moths (p=0.007) (Figure 1). In the period between 12-30 months an increase in POAF burden was observed for all groups (p<0.001), however the burden remained lower as compared to the first 3 postoperative months (Figure 1). Univariable differences between patients with and without progression of POAF-burden are shown in Table 1. Multivariable analysis showed no independent predictors of POAF-burden progression. Individual postoperative POAF-burden was strongly associated with the longest POAF-episode (Spearman’s rho=0.86, 95%CI: 0.75-0.92, p<0.001), and to a lower extent with the duration of the median episode (Spearman’s rho=0.38, 95%CI: 0.13-0.58, p=0.001). Patients developing POAF have the highest POAF-burden in the first 3 postoperative months. Increased atrial volumes and reduced atrial ejection fraction seem to be associated with AF-burden progression. Also, AF-burden seems to be highly correlated to the longest individual episode duration.

Effects and mechanism of Compound Qidan Formula on rats with HFpEF induced by hypertension and diabetes mellitus based on Ang Ⅱ/TGF-β1/Smads signaling pathway

Ethnopharmacological relevanceCompound Qidan Formula is composed of traditional Chinese herbs and has a good curative effect in the clinical application of cardiovascular diseases such as heart failure. However, its potential molecular mechanisms of action remain highly unknown. Aim of the studyTo observe the effect of Compound Qidan Formula on cardiac function in rats with HFpEF induced by hypertension and diabetes mellitus, and to explore its mechanism from Ang Ⅱ/TGF-β1/Smads signaling pathway. Materials and methodsA total of 50 SPF-grade spontaneously hypertensive rats (SHR) aged 14 weeks, fed with a high-fat and high-sucrose diet for 16 weeks, and after 2 weeks of a high-fat and high-sucrose diet, 1% streptozotocin (25 mg/kg body weight)was injected intraperitoneally to establish a rat model of HFpEF induced by hypertension and diabetes mellitus. After 8 weeks of intragastric administration, the changes in cardiac morphology and function were evaluated by echocardiography after anesthesia; the heart tissue was taken and embedded in paraffin for Masson staining, and the pathomorphological changes of left atrial tissue were observed under the optical microscope; the mRNA transcription levels of Ang Ⅱ, AT1R, TGF-β1, Smad2, Smad3, MMP-9 and TIMP-1in left atrial tissue of rats were detected by RT-PCR; and the protein expressions were detected by Western blot. ResultsCompared with the SHR-DM group, the QD-Low and QD-High groups significantly decreased the left atrial (LA) anteroposterior diameter and interventricular septal thickness (IVST) and improved the peak velocity of mitral valve blood flow in early diastolic period (E), maximum mitral valve blood flow in systolic period (A), mitral ring myocardial movement velocity in early diastolic period (e’) and E/e' ratio; the QD-High group significantly improved the E/A ratio, left atrial ejection fraction (LAEF) and left ventricular ejection fraction(LVEF). Masson staining showed that compared with the WKY group, the SHR-DM group had obvious myocardial histomorphological lesions. Compared with the SHR-DM group, the Compound Qidan Formula groups significantly improved cardiomyocyte hypertrophy and disordered arrangement and inhibited myocardial fibrosis; the mRNA expression levels of Ang Ⅱ, AT1R, TGF-β1, Smad2, Smad3, and MMP-9 in myocardial tissue of Compound Qidan Formula groups were significantly decreased, and the mRNA expression level of TIMP-1 was significantly increased. The protein expression levels of Ang Ⅱ, TGF-β1, P-Smad2/3, and MMP-9 were significantly decreased. ConclusionCompound Qidan Formula, composed of traditional Chinese herbs, can significantly improve cardiac function, improve atrial and ventricular remodeling, and prevent myocardial fibrosis and hypertrophy in rats with HFpEF induced by hypertension and diabetes mellitus. The mechanism may be related to regulating the Ang Ⅱ/TGF-β1/Smad2/3 signaling pathway.

Atrial fibrillation episode status and incidence of coronary slow flow: A propensity score-matched analysis.

Previous studies have shown that patients with a history of atrial fibrillation (AF) have a higher risk of developing coronary slow flow (CSF). However, whether AF episode status affects the incidence of CSF has not been confirmed. This study investigated the correlation between AF episode status and the incidence of CSF. We enrolled patients with AF who underwent coronary angiography for symptoms of myocardial ischemia between January 1, 2017, and April 30, 2022, at our institution and classified them according to whether they had an episode of AF in the perioperative period. The outcomes were defined the occurrence of CSF overall and in each of the three coronary arteries. The analysis was repeated after adjusting the baseline information by the propensity score matching method in a 1:1 ratio. 214 patients who met the inclusion and exclusion criteria were included in the study (AF episode group: 100 patients, AF non-episode group: 114 patients). Before matching, age, left atrial size, ejection fraction, heart rate, CSF incidence, and mean corrected thrombolysis in myocardial infarction frame counts were higher in patients with intraoperative AF episodes than in patients without episodes. To prevent the dependent variable (CSF incidence) from being confounded by confounding factors, we matched the two groups for age, left atrial size, and ejection fraction. In the logistic regression analysis, the incidence of CSF was significantly higher in the intraoperative AF episode group (P = 0.010, OR = 2.327, 95% CI: 1.226-4.416) than in the non-episode group. In patients with AF, AF episode status is significantly correlated with an increased overall incidence of CSF.

Cardiovascular magnetic resonance rest and exercise-stress left atrioventricular coupling index to detect diastolic dysfunction.

Left atrial and ventricular (LA/LV) dysfunction are interlinked in heart failure with preserved ejection fraction (HFpEF); however, little is known about their interplay and relation to cardiac decompensation. We hypothesized that cardiovascular magnetic resonance (CMR) left atrioventricular coupling index (LACI) would identify pathophysiological alterations in HFpEF and be amenable to rest and ergometer-stress CMR. Patients with exertional dyspnoea, signs of diastolic dysfunction (E/e' ≥ 8), and preserved ejection fraction (EF; ≥50%) on echocardiography were prospectively recruited and classified as HFpEF (n = 34) or noncardiac dyspnoea (NCD, n = 34) according to pulmonary capillary wedge pressure (PCWP) on right-heart catheterization (rest/stress ≥ 15/25 mmHg). LA and LV volumes were assessed on short-axis real-time cine sequences at rest and during exercise stress. LACI was defined as the ratio of the LA-to-LV end-diastolic volume. Cardiovascular hospitalization (CVH) was assessed after 24 mo. Volume-derived LA (P ≥ 0.008) but not LV (P ≥ 0.347) morphology and function at rest and during exercise stress detected significant differences comparing HFpEF and NCD. There was impaired atrioventricular coupling in HFpEF at rest (LACI, 45.7% vs. 31.6%, P < 0.001) and during exercise stress (45.7% vs. 27.9%, P < 0.001). LACI correlated with PCWP at rest (r = 0.48, P < 0.001) and during exercise stress (r = 0.55, P < 0.001). At rest, LACI was the only volumetry-derived parameter to differentiate patients with NCD from patients with HFpEF, which were identified using exercise-stress thresholds (P = 0.001). Resting and exercise-stress LACI dichotomized at their medians were associated with CVH (P ≤ 0.005). Assessment of LACI is a simple approach for LA/LV coupling quantification and allows easy and fast identification of heart failure with preserved ejection fraction (HFpEF).NEW & NOTEWORTHY Evaluation of the left atrioventricular coupling index (LACI) in a rest and exercise-stress cardiovascular magnetic resonance imaging protocol allows identification of patients with heart failure and preserved ejection fraction with high diagnostic accuracy. LACI holds similar diagnostic accuracy at rest compared with left atrial ejection fraction during exercise stress. This highlights the value of LACI as a widely available and cost-effective test for diastolic dysfunction, which may help to guide patient selection for referral to specialized testing/treatment.

Assessment of fetal left atrial volume and function using anovel left atrial volume tracking method.

Several fetal cardiovascular structural defects may alter the hemodynamics of the cardiac chambers resulting in changes in chamber sizes. Quantitative measurements of the sizes of cardiac chambers can augment the diagnostic power of fetal echocardiography. Using a new left atrial volume tracking (LAVT) method, time-left atrial volume curves (TLAVCs) can be automatically obtained. The goal of this study was to examine whether this method can be used to evaluate left atrial volume (LAV) and provide reference values for LAV and indices of left atrial function in normal human fetuses. Two hundred and four normal human fetuses were enrolled. Using LAVT, the maximal left atrial volume (LAVmax) and minimal left atrial volume (LAVmin) were measured from TLAVCs. Left atrial ejection fraction (EF) was calculated. The maximal left atrial area (LAAmax) and minimal left atrial area (LAAmin) were measured using manual method tracing. Between 21 and 40 weeks, mean LAVmax increased from 0.27 ml to 4.15 ml, and mean LAVmin increased from 0.13 ml to 2.26 ml, respectively, while the EF remained stable at around 0.43. From 21 to 40 weeks, mean LAAmax increased from 0.61 cm2 to 2.64 cm2, and mean LAAmin increased from 0.34 cm2 to 1.53 cm2. This study establishes reference values for fetal LAV during the second half of gestation. The LAVT method appears to be feasible in estimating fetal LAV and shows potential for assessing left atrial function.