LA Function Research Articles

Abstract 4135617: Large Scale Proteomics Identifies Circulating Biomarkers Relating Atrial Fibrillation to Heart Failure: the Atherosclerosis Risk in Communities Study

Introduction: There is a bidirectional relationship between atrial fibrillation (AF) and heart failure (HF) risk. Data regarding shared and unique pathways underlying each are limited. Aims: Identify plasma proteins associated with both incident AF and HF and determine the extent to which associations with one outcome are conditional on interval occurrence of the other outcome. Methods: Among participants in the community-based Atherosclerosis Risk in Communities study free of HF and AF at study visit 5 (2011-2013), we measured 4,955 plasma proteins (SomaScan aptamer-affinity assay). We performed parallel analyses of individual protein associations with incident HF and AF using multivariable Cox regression adjusted for demographic and clinical covariates at Bonferroni significance. We then repeated the analysis for each outcome in models censoring participants with interval occurrence of the other outcome (i.e. incident AF censoring for interval HF, and vice versa). We tested associations of AF-related proteins with echocardiographic and Zio patch measures at Visit 5. Results: Among 4,118 participants included, mean age was 75±5 years, 60% were female, and 18% reported Black race. We identified 83 proteins associated with incident HF (n=355 incident events at 7 [IQR 6-8] year follow-up) and 24 with incident AF (n=517 incident events at 8 [7-9] years), of which 10 were associated with both. In models of incident HF censoring for interval AF, 63 (76%) proteins remained significantly associated with HF. In contrast, in the analysis of incident AF censoring for interval HF, only 4 (17%) proteins remained associated with AF, of which 3 were also associated with HF risk (Figure). These 4 AF-related proteins were associated with measures of LV diastolic function (LA volume, E/e’. average), LV mass index, LA function (LA reservoir, LA contraction), and supraventricular ectopy density (all p<0.05). Conclusion: Nearly half of proteins reflecting AF risk also associate with HF, greater than 80% of AF-associated proteins are HF-dependent, and even those that are not correlate with measures of LV remodeling and dysfunction. These findings suggest that AF-related mechanisms among older adults are part of a wider HF syndrome.

Atrial fibrillation substrate and impaired left atrial function: a cardiac MRI study.

Structural and fibrotic remodelling is a well-known contributor to the atrial fibrillation (AF) substrate. Epicardial adipose tissue (EAT) is increasingly recognized as a contributor through electrical remodelling in the atria. We aimed to assess the association of LA fibrosis and EAT with LA strain and function using cardiac magnetic resonance (CMR) imaging in patients with AF. LA fibrosis was assessed using late gadolinium enhancement CMR, LA EAT was assessed using the fat-water separation Dixon sequence, and feature tracking was applied to assess global longitudinal strain in its three components [reservoir (GLRS), conduit (GLCdS), and contractile (GLCtS)]. LA emptying fraction and LA volume were measured using the cine sequences. All CMR images were acquired in sinus rhythm. One hundred one AF patients underwent pre-ablation CMR (39% female, average age 62 years). LA fibrosis was negatively associated with the three components of global longitudinal strain (GLRS: R = -0.35, P < 0.001; GLCdS: R = -0.24, P = 0.015; GLCtS: R = -0.2, P = 0.046). Out of the different sections of the LA, fibrosis in the posterior and lateral walls was most negatively correlated with GLRS (R = -0.32, P = 0.001, and R = -0.33, P = 0.001, respectively). LA EAT was negatively correlated with GLCdS (R = -0.453, P < 0.001). LA fibrosis was negatively correlated with LA emptying fraction but LA EAT was not (R = -0.27, P = 0.007, and R = -0.22, P = 0.1, respectively). LA EAT and fibrosis were both positively correlated with LA volume (R = 0.38, P = 0.003, and R = 0.24, P = 0.016, respectively). LA fibrosis, a major component of the AF substrate, and EAT, an important contributor, are associated with a worsening LA function through strain analysis by CMR.

Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy.

Obesity is a known risk factor for heart failure with preserved ejection fraction (HFpEF) and is considered a distinct phenotype with more concentric remodeling. Epicardial adipose tissue (EAT) is also increased in obesity-related HFpEF and is associated with adverse events. The Cardiac Magnetic Resonance (CMR) Substudy of the SUMMIT trial was aimed to examine the effects of tirzepatide on cardiac structure and function with the underlying hypothesis that it would reduce left ventricular (LV) mass and EAT in obesity-related HFpEF. One hundred seventy-five patients with obesity-related HFpEF from the parent study of tirzepatide (2.5mg SQ weekly, increasing to a maximum of 15mg weekly) or matching placebo underwent CMR at baseline, which consisted of multiplanar cine imaging. One hundred six patients completed the CMR and had adequate image quality for analysis of LV and LA structure and function and paracardiac (epicardial plus pericardial) adipose tissue at both baseline and 52 weeks. The prespecified primary endpoint of this substudy was between-group changes in LV mass. LV mass decreased by 11 g (95% C.I. -19 to -4) in the treated group (n = 50) when corrected for placebo (n =56) (p=0.004). Paracardiac adipose tissue decreased in the treated group by 45 ml (95% C.I. -69 to -22) when corrected for placebo (p<0.001). The change in LV mass in the treated group correlated with changes in body weight (p<0.02) and, tended to correlate with changes in waist circumference and blood pressure (p=0.06 for both). The LV mass change also correlated with changes in LV end diastolic volume and LA end diastolic and end systolic volumes (p<0.03 for all). The CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared to placebo and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial.

Association between CHA2DS2-VASc score and left atrial function by speckle tracking echocardiography in patients with sinus rhythm

Abstract Background The CHA2DS2-VASc score is a scoring system that was first used for the risk assessment of cerebrovascular or thromboembolic events in patients with atrial fibrillation (AF). The factors that constitute the CHA2DS2-VASc scoring system can all individually have an impact on LA function. The application of this scoring system can also be applied to patients without AF. The LA structural remodeling and/or functional impairment play a part in the pathogenesis and development of AF and independent of rhythm, may result in atrial hemostasis and confer a prothrombotic diathesis, resulting in thromboembolic stroke. Speckle- tracking echocardiography (STE) makes it possible to measure LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement. Purpose The aim of our study was to assess the left atrial function in patients with sinus rhythm with different CHA2DS2-VASc scores (low, moderate and high) by speckle tracking echocardiography and to identify the association between them. Methods This study was conducted using prospectively collected data (1st May, 2022 to 30th October 2022) from patients with sinus rhythm and different CHA2DS2-VASc scores (50 Low risk score patients (1 for females and 0 for males), 50 moderate risk score patients (2 for females and 1 for males) and 50 high risk score patients (≥3 for females and ≥2 for males) After obtaining an informed consent, all volunteers underwent thorough history taking, 12 lead ECG and conventional transthoracic echocardiography and speckle-tracking echocardiography. Results LA strain during the reservoir (LASr) and conduit phases (LAScd) were statistically significantly lower in the high-risk score group (33.2 ± 7.1 and 20.3 ± 5.7) than the moderate-risk score group (36.9 ± 6.1 and 23.5 ± 4.8, p = 0.005 and 0.003 respectively) and low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9, p &amp;lt; 0.001). In addition, LASr and LAScd were statistically significantly lower in moderate- risk score group (36.9 ± 6.1 and 23.5 ± 4.8) than the low -risk score group (40.6 ± 5.6 and 26.9 ± 3.9 ,p=0.007 and 0.001 respectively). Conclusion Higher CHA2DS2-VASc scores were associated with decreased LA strain during the reservoir and conduit phases as markers of LA function with relatively high accuracy and at the very early stage even in the absence of LA enlargement.

Serial changes in left atrial strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from VALOR-HCM trial

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, a cardiac myosin inhibitor, reduces the eligibility for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Mavacamten also resulted in favorable cardiac remodeling, including improvement in left atrial volume index (LAVI), LV diastolic function, and biomarkers (NT-proBNP and troponin T). However, the impact of mavacamten on LA function is not known. Objective We sought to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean age 60 years, 51% male). Patients assigned to mavacamten at baseline (n=56) continued therapy for 56 weeks and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). Echocardiographic LA strain assessment was performed according to the current American and European guideline recommendations, using a vendor-neutral post processing software. For assessment of LA strain components (reservoir, conduit, and contraction), the non-foreshortened apical 4-chamber view was utilized. The zero reference was set at end-diastole. Results Serial changes in LAVI and all components of mean LA strain from baseline to week 56 are shown in the Figure. At baseline, LAVI and all mean LA strain values were worse than reported normal mean thresholds. There was a continued and significant improvement in all 3 LA strain values, from baseline to week 56, along with a significant reduction in LAVI. Improvement in LAVI was seen earlier than improvements in LA strain. There was a significant inverse correlation between change in mean LAVI and LA reservoir strain from baseline to week 56 (r= -0.42, p&amp;lt;0.001). Conclusions In the VALOR-HCM trial, average LAVI and baseline LA strain values were significantly worse than reported normal thresholds. Treatment with mavacamten resulted in an improvement in LAVI and LA strain values from baseline through week 56 suggesting a sustained favorable impact on cardiac remodeling. The advantageous cardiac remodeling associated with long-term treatment with mavacamten may in turn have a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM.Serial changes in LA strain in VALOR-HCM

Novel method in mice to evaluate left atrial (LA) systolic contribution to left ventricular volume (LV) using pressure-volume (PV) loops

Abstract Background LA myopathy is a critically important non-LV contributor to the progression of HFpEF (heart failure with preserved ejection fraction) in patients and is associated with a severe phenotype, leading to impaired cardiac output reserve and reduced exercise capacity. In normal humans LA systole contributes ~20% of total LV filling, but with HFpEF, this contribution decreases to &amp;lt;16% with a greater reliance on this contribution to LV filling. Purpose We sought to investigate LA function as a critical component of cardiac function analysis by utilizing the LV pressure signal to identify and quantify the contribution of volume during LA systole to the total LV volume in mice with HFpEF. Methods Hypertension (HTN)-associated HFpEF C57BL/6J mice were subjected to chronic aldosterone infusion and 1% NaCl for 4 weeks (SAUNA model). Obesity after a high fat diet (HFD: 60% fat diet) for 16 weeks followed by the SAUNA protocol, induced HTN and obesity associated HFpEF. Blood pressure was monitored weekly. Mice were anesthetized with isoflurane, intubated, chest opened to expose the heart and allow placement of a PV catheter (Transonic) which was introduced into the LV via apical stab with a 27G needle. Calibration of the PV catheter was performed according to the manufacturer’s instructions. Atrial systole was identified using 2nd order derivative of the LV pressure signal. Contribution of LA systole was calculated using volume at the beginning of LA systole identified by the 2nd order derivative of the LV pressure signal and subtracting from the LV end diastolic volume. The % of LA systole contribution was calculated as a % of the total LV stroke volume. Data was analyzed with LabChart pro software (AD Instruments). Results SAUNA mice had normal LVEF, moderate HTN and lung congestion. PV relationships demonstrated Tau was impaired in HFpEF vs. control mice (14±1 vs. 10±0.5 ms) with a shift of the PV loop to the left (Fig. A.) In control mice, the atrial systole contributed 39± 4% to LV volume and was impaired in HFpEF mice 20± 3% a 1.95-fold reduction (P&amp;lt;0.01). Importantly atrial systole contribution was increased in obese mice 53±5 %. However, the combination of obesity and HTN, both common comorbidities in HFpEF, resulted in a reduced LA systole contribution by 1.43-fold to 37± 9%, (P&amp;lt;0.005; Fig B). Conclusion A novel method of % atrial systole from LV PV loop using 2nd order derivative to quantify the volume contribution of atrial systole to total LV stroke volume was identified in mice. LA dysfunction was present in murine HTN-associated HFpEF with/without obesity.

Clustering analysis based on clinically available data for improving risk stratification and outcome prediction of hypertension

Abstract Background Hypertension (HTN) is a heterogeneous condition with several factors contributing to adverse outcomes. Machine learning can harness complex data to unveil outcome predictors and guide prevention. Purpose To use clustering analysis on clinical data to identify HTN risk profiles and their associations with cardiovascular abnormalities and clinical outcomes. Methods A cohort of 14,840 UK Biobank hypertensive participants without pre-existing heart failure (HF) who underwent cardiovascular magnetic resonance (CMR) assessment was examined using K-means clustering on 79 clinical attributes. The clusters’ association with incident HF, mortality, atrial fibrillation (AF), and major adverse cardiovascular events (MACE) were evaluated, alongside imaging characteristics, with mediation analysis probing the role of imaging in risk differentiation. All post-hoc analyses were adjusted for vascular risk factors (VRFs), including diabetes, hypercholesterolaemia, previous myocardial infarction. Results Three distinct clusters differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles were identified. Cluster 1 (lowest risk), predominantly females, exhibited the most favourable metabolic profile and outcomes. Cluster 2 (highest risk), predominantly males, had the most adverse metabolic and cardiovascular profiles, and the highest risk of all adverse outcomes, especially AF and HF (hazard ratio (HR) 1.80 [1.45–2.25] and 1.85 [1.39–2.46]; p &amp;lt;0.005). This group was associated with more eccentric LV hypertrophy (LVH), overall poorer left atrial emptying function (LAEF), bi-ventricular systolic function and LV mechanics, and higher systemic vascular resistance (Figure 1). Cluster 3 (intermediate risk) was a more heterogeneous group with the highest burden of diabetes and adiposity and a moderate rise in AF and MACE risk (HR 1.61 [1.12-2.32] and 1.30 [1.07-1.58]; p &amp;lt;0.05). This cluster was associated with concentric LV remodelling and better indices of cardiac mechanics, but greater impairment in LA booster pump function (active LAEF) than Cluster 2 (Figure 1). Cluster 2's effect on MACE was mostly mediated through LV mass increase (proportion mediated, 67%), followed by changes (reducing) in LV global longitudinal strain (33%), and ejection fraction (25.4%). The indirect effect of CMR changes in the association between cluster 3 and MACE was much smaller with the highest proportion of the effects mediated through increased myocardial wall thickness (26%) but not LV mass, and changes in all the components of LA function. Conclusions Clinical data clustering provides insight into distinct HTN risk profiles, each with specific imaging characteristics and clinical trajectories, hinting at different pathophysiological mechanisms. Enhanced phenotyping can facilitate tailored interventions based on the disease subtype and improve clinical outcomes.Figure 1.

Left atrial strain measured by three-dimensional echocardiography predicts atrial fibrillation in the general population

BackgroundLeft atrial (LA) strain by three-dimensional echocardiography (3DE), has been proposed as a more accurate measure of LA function, providing incremental prognostic benefits over traditional two-dimensional approaches. ObjectivesOur aim was to evaluate the prognostic value of LA strain by 3DE in predicting incident atrial fibrillation (AF) in the general population. MethodsThe study included 4466 participants from a prospective longitudinal cohort study in the general population, among these 3DE LA strain was analysed in 1935 participants. The endpoint was incident AF. Adjustments were made for the CHARGE-AF clinical risk score. ResultsMean age was 54 ± 17 years, 43 % were male. During a median follow-up time of 4.8 years (interquartile range 4.3–5.5 years) 59 participants (3.0 %) developed AF. In univariable analysis, all three parameters were associated with incident AF (p value for all <0.01). After multivariable adjustments, only LA reservoir strain (LASr) and LA contractile strain (LASct) were associated with incident AF (LASr: HR 1.12 (1.07–1.17), p < 0.001, per 1 % decrease; LASct: HR 1.16 (1.09–1.24), p < 0.001, per 1 % decrease), whereas LA conduit strain (LAScd) was not (HR 1.04 (0.98–1.10), p = 0.17, per 1 % decrease). Both LASr (continuous net reclassification index 0.37 ± 0.14; p = 0.003) and LASct (continuous net reclassification index 0.41 ± 0.14; p = 0.002) provided incremental prognostic information beyond the CHARGE-AF risk score. ConclusionLASr and LASct measured by 3DE are independently associated with incident AF and provided incremental prognostic information beyond existing risk scores.

The Effect of Upright Posture on Left Atrial Strain in Competitive Athletes.

Left atrial strain (LAS) assessment by speckle tracking echocardiography (STE) has been shown to be a remarkable means of quantifying LA function as an early marker of LV pathology. As exercise testing is also performed on a treadmill, the aim of this study was to investigate the effect of upright posture on LAS in healthy athletes. Fifty male athletes (mean age 25.7 ± 7.3 years) underwent transthoracic echocardiography (TTE) in the upright and left lateral positions. In addition to the conventional echocardiographic parameters, in all athletes, LA conduction strain (LAScd), contraction strain (LASct), reservoir strain (LASr), and maximum LA volume (LAVmax) were assessed by STE in both positions. Comparing upright posture and the left lateral position, LAScd (-14.0 ± 5.9% vs. -27.4 ± 7.1%; p < 0.001), LASct (-4.6 ± 3.5% vs. -11.3 ± 4.1%; p < 0.001), LASr (18.7 ± 7.6% vs. 38.7 ± 8.0%; p < 0.001), and LAVmax (24.4 ± 8.8% vs. 50.0 ± 14.2%) differed significantly. Upright posture has a significant effect on LA deformation, with decreased LAScd, LASct, and LASr. The results of this study contribute to the understanding of athletes' hearts and must be considered when performing echocardiography in healthy athletes on a treadmill.

Effects of prosthesis-patient mismatch on cardiac function and clinical outcome after transcatheter aortic valve implantation

Abstract Background Transcatheter aortic valve implantation (TAVI) prostheses have better hemodynamics compared to surgical prostheses, with a lower incidence of prosthesis-patient mismatch (PPM). Nonetheless, the effects of PPM have been controversial regarding clinical impact. This study aims to determine the short-term impact of PPM on cardiac function and the effect of PPM on mid-term outcome in patients undergoing transfemoral TAVI with balloon-expandable valves. Methods One hundred sixty consecutive patients (76.5±7.4 years, 85 men) were enrolled and examined before and 30 days after TAVI, by comprehensive echocardiogram (speckle tracking echocardiography and strain analysis). Patients were divided according to measured PPM (PPMM) into PPMM group: indexed effective orifice area (EOAi)≤0.85 cm2/m2 (n=64), and No-PPMM group: EOAi&gt;0.85 cm2/m2 (n=96). Predictors and predictive value of PPMM were analyzed based on the primary endpoint, 3-year all-cause mortality. Results Impaired LA function was independently associated with PPMM after TAVI (global LA strain - OR 0.92, p = 0.022). Three-year mortality was higher in the PPMM group (23.4% vs. 10.4% in the No-PPMM group, p=0.026). Conclusions Our study revealed significantly worse impairment of LA function in patients with PPMM compared to those without PPMM on short-term follow-up, which correlated with 3-year mortality.

The impact of diabetes mellitus on cardiac function assessed by magnetic resonance imaging in patients with hypertrophic cardiomyopathy

BackgroundThe adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM).MethodsA total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression.ResultsCompared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (β = − 6.05, P < 0.001) and impaired global longitudinal strain (β = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (β = − 45.81, P = 0.008), LV global circumferential strain (β = 18.25, P = 0.003), LA reservoir strain (β = − 59.20, P < 0.001) and strain rate (β = − 2.90, P = 0.002).ConclusionsDiabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.

Determinants of invasive left atrial pressure in patients with atrial fibrillation.

Estimation of left ventricular (LV) filling pressures in patients with a history of atrial fibrillation (AF) is challenging due to lack of reliable parameters. This study investigates the association between cardiac structure and function and invasive mean left atrial pressure (LAP). This is a multi-centre prospective study enrolling patients undergoing transcatheter ablation for AF. The invasive measurement of LAP was performed at the time of the procedure while the echocardiography within the previous 24 h. A mean LAP ≥ 15 mmHg was considered as increased. Overall, 101 patients were included (mean age 65.8 ± 8.5 years, 68% male, mean LV ejection fraction 56.6 ± 8.0%). No significant differences regarding clinical characteristics were detected between the group of patients with normal (n = 47) or increased LAP (n = 54). The latter showed lower values of LV global longitudinal strain, larger left atrial volumes (LAVs) and worse right ventricular (RV) function. After multivariable adjustment, higher E/e' ratio (P = 0.041) and minimal LAV index (LAVI min) (P = 0.031), lower peak atrial longitudinal strain (P = 0.030), and RV free wall longitudinal strain (P = 0.037), but not maximal LAV index (LAVI max) (P = 0.137), were significantly associated with mean LAP. The associations were not modified by cardiac rhythm. Overall, LAVI min showed the best diagnostic accuracy to predict elevated LAP (area under the curve 0.703). LA structure and function assessment well correlates with mean LAP in patients with a history of AF. These measures may be used in the assessment of filling pressure in these patients.

Impact of maternal diabetes mellitus on fetal atrial strain.

While Maternal Diabetes Mellitus (DM) is well known to affect the size and function of multiple fetal organ systems, effects on developing heart chamber function remain difficult to assess. We sought to determine the independent impact of maternal DM on fetal cardiac function in middle pregnancy. We prospectively recruited mothers with all categories of DM and non-diabetic healthy controls (NDC). Echocardiograms were optimized for chamber quantification and strain analysis. Left atrial area (LAA), LA strain (LAS), right atrial strain (RAS), global longitudinal ventricular strain (GLS) and Right ventricular free wall strain (RV FWS) were evaluated by 2 blinded operators. After excluding 9 mothers with poor fetal image quality, images from 104 mothers with DM and 47 NDC were analyzed. Mothers with DM and NDCs were well matched for age, blood pressure, smoking prevalence, and gestational age. Fetal heart rate (FHR) was significantly higher in fetuses of mothers with DM compared to NDC (147 ± 10bpm vs. 144 ± 8, p = 0.04). LAA in fetuses of mothers with DM trended towards being larger in size (1.68 ± 0.4cm2 vs. 1.56 ± 0.4cm2, p = 0.08). Fetal septal diameters were larger in maternal DM compared to NDC (2.7 ± 0.5cm vs. 2.5 ± 0.5cm, p = 0.001). GLS was similar between the groups. Fetal LAS was lower in maternal DM (28.8 ± 8.8% vs. 33.3 ± 10.4%, p = 0.007) and was independently associated with maternal DM after adjusting for GLS and FHR. Fetal RAS was lower in maternal DM (27.7 ± 10.4% vs. 31.8 ± 10.3%, p = 0.007), however only determinates were estimated fetal weight and RV FWS. Maternal DM independently impairs fetal LA function in mid pregnancy. These early functional changes in the developing heart warrant future studies investigating impact on cardiovascular health.

Role of NOD1 in atrial myopathy associated with heart failure

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funding: Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ISCIII [PI17/01344 and PI20/01482]), Ministry of Education (FPU19/01973), SEC, Proyecto Traslacional 2019, FEDER, FSE, CIBER-CV, a network funded by ISCIII Introduction Heart failure (HF) is a complex syndrome that constitutes one of the leading causes of cardiovascular death worldwide. Although multifactorial mechanisms appear to be responsible of atrial and ventricular HF-myopathy, the innate immune system and the derived inflammatory response have gained much attention in the last years. Previous studies from our group have demonstrated that the nucleotide-binding oligomerization domain 1 (NOD1), a receptor of the innate immune system, plays a role in HF left ventricular (LV) dysfunction. However, its role in HF-atrial myopathy remains completely unknown. The main purpose of our study is to determine the role of NOD1 in human and experimental HF-atrial myopathy. Methods and Results The study was performed in two cohorts of individuals who underwent heart valve repair surgery, 51 non-failing individuals (NF) with LV ejection fraction (LVEF)&amp;gt;50% and NT-ProBNP levels&amp;lt;200pg/mL and 41 subjects with medium to severe reduced EF (HF)&amp;lt;50% and NT-ProBNP levels&amp;gt;200pg/mL. An informed consent was signed by all patients. Atrial myocardial tissue was excised from the atrial appendage and prepared for biochemical and histological studies. Echocardiography analysis showed that left and right atrial areas (LA and RA) were significantly increased in the HF group compared to NF, while LA and RA reservoir functions were significantly decreased in HF. Immunostaining demonstrated NOD1 location in atrial cardiomyocytes, being the protein levels of NOD1 and its specific adaptor RIP2 significantly increased in atrial tissue obtained from HF vs. NF. Although the prevalence of atrial fibrillation (AF) was significantly higher in the HF group compared to NF, the upregulation of NOD1 was not conditioned by the presence of AF. Similarly, pigs that underwent transverse aortic constriction (TAC) or proximal left circumflex coronary artery occlusion involving the LA branch (LAI), showed an upregulation of NOD1 pathway in atrial tissue, compared with the sham operated animals. Interestingly, an atrial upregulation of NOD1 axis was also observed in wild-type TAC mice, whereas Nod1-/- knockout mice showed a prevention in both structural and functional atrial remodelling induced by TAC, mainly by a prevention of intracellular calcium mishandling in isolated atrial cardiomyocytes. Finally, wild-type mice injected i.p. for 3 days with 3.3 mg/kg with a selective activator of NOD1, showed increased structural atrial remodelling and intracellular calcium mishandling compared to the vehicle-treated group. Conclusions Our results demonstrate that NOD1 axis is upregulated in human, swine and murine atrial failing myocardium. Genetic deletion of NOD1 prevented HF-atrial structural and functional remodelling, mainly by avoiding intracellular calcium mishandling, whereas its pharmacological activation induced atrial dilation and intracellular Ca2+ mishandling. All these data uncover NOD1 as a new player in atrial HF-remodelling.

Associations between 3D-based Left Atrial Volumetric and Blood Flow Parameters in a Single-Site Cohort of the Multi-Ethnic Study of Atherosclerosis.

Purpose To investigate associations between left atrial volume (LAV) and function with impaired three-dimensional hemodynamics from four-dimensional flow MRI. Materials and Methods A subcohort of participants from the Multi-Ethnic Study of Atherosclerosis from Northwestern University underwent prospective 1.5-T cardiac MRI including whole-heart four-dimensional flow and short-axis cine imaging between 2019 and 2020. Four-dimensional flow MRI analysis included manual three-dimensional segmentations of the LA and LA appendage (LAA), which were used to quantify LA and LAA peak velocity and blood stasis (% voxels < 0.1 m/sec). Short-axis cine data were used to delineate LA contours on all cardiac time points, and the resulting three-dimensional-based LAVs were extracted for calculation of LA emptying fractions (LAEFtotal, LAEFactive, LAEFpassive). Stepwise multivariable linear models were calculated for each flow parameter (LA stasis, LA peak velocity, LAA stasis, LAA peak velocity) to determine associations with LAV and LAEF. Results This study included 158 participants (mean age, 73 years ± 7 [SD]; 83 [52.5%] female and 75 [47.4%] male participants). In multivariable models, a 1-unit increase of LAEFtotal was associated with decreased LA stasis (β coefficient, -0.47%; P < .001), while increased LAEFactive was associated with increased LA peak velocity (β coefficient, 0.21 cm/sec; P < .001). Furthermore, increased minimum LAV indexed was most associated with impaired LAA flow (higher LAA stasis [β coefficient, 0.65%; P < .001] and lower LAA peak velocity [β coefficient, -0.35 cm/sec; P < .001]). Conclusion Higher minimum LAV and reduced LA function were associated with impaired flow characteristics in the LA and LAA. LAV assessment might therefore be a surrogate measure for LA and LAA flow abnormalities. Keywords: Atherosclerosis, Left Atrial Volume, Left Atrial Blood Flow, 4D Flow MRI Supplemental material is available for this article. © RSNA, 2024.

Adiposity influences on myocardial deformation: a cardiovascular magnetic resonance feature tracking study in people with overweight to obesity without established cardiovascular disease

The objective of this study was to assess whether dietary-induced weight loss improves myocardial deformation in people with overweight to obesity without established cardiovascular disease applying cardiovascular magnetic resonance (CMR) with feature tracking (FT) based strain analysis. Ninety people with overweight to obesity without established cardiovascular disease (age 44.6 ± 9.3 years, body mass index (BMI) 32.6 ± 4 kg/m2) underwent CMR. We retrospectively quantified FT based strain and LA size and function at baseline and after a 6-month hypocaloric diet, with either low-carbohydrate or low-fat intake. The study cohort was compared to thirty-four healthy normal-weight controls (age 40.8 ± 16.0 years, BMI 22.5 ± 1.4 kg/m2). At baseline, the study cohort with overweight to obesity without established cardiovascular disease displayed significantly increased global circumferential strain (GCS), global radial strain (GRS) and LA size (all p < 0.0001 versus controls) but normal global longitudinal strain (GLS) and normal LA ejection fraction (all p > 0.05 versus controls). Dietary-induced weight loss led to a significant reduction in GCS, GRS and LA size irrespective of macronutrient composition (all p < 0.01). In a population with overweight to obesity without established cardiovascular disease subclinical myocardial changes can be detected applying CMR. After dietary-induced weight loss improvement of myocardial deformation could be shown. A potential clinical impact needs further studies.

Exercise echocardiography to assess left atrial function in patients with symptomatic AF

BackgroundLeft atrial (LA) function contributes to the augmentation of cardiac output during exercise. However, LA response to exercise in patients with atrial fibrillation (AF) is unknown. We explored the LA mechanical response to exercise and the association between LA dysfunction and exercise intolerance. MethodsWe recruited consecutive patients with symptomatic AF and preserved left ventricular ejection fraction (LVEF). Participants underwent exercise echocardiography and cardiopulmonary exercise testing (CPET). Two-dimensional and speckle-tracking echocardiography were performed to assess LA function at rest and during exercise. Participants were grouped according to presenting rhythm (AF vs sinus rhythm). The relationship between LA function and cardiorespiratory fitness in patients maintaining SR was assessed using linear regression. ResultsOf 177 consecutive symptomatic AF patients awaiting AF ablation, 105 met inclusion criteria; 31 (29.5 %) presented in AF whilst 74 (70.5 %) presented in SR. Patients in SR augmented LA function from rest to exercise, increasing LA emptying fraction (LAEF) and LA reservoir strain. In contrast, patients in AF demonstrated reduced LAEF and reservoir strain at rest, with failure to augment either parameter during exercise. This was associated with reduced VO2Peak compared to those in SR (18.4 ± 5.6 vs 22.5 ± 7.7 ml/kg/min, p = 0.003). In patients maintaining SR, LAEF and reservoir strain at rest and during exercise were associated with VO2Peak, independent of LV function. ConclusionThe maintenance of SR in patients with AF is associated with greater LA reservoir function at rest and greater augmentation with exercise compared to patients in AF. In patients in SR, reduced LA function is associated with reduced exercise tolerance, independent of LV function.

The impact of extensive ablation strategy for persistent atrial fibrillation on left atrial function and cardiovascular events: Insights from EARNEST-PVI randomized controlled trial

Abstract Background Left atrial (LA) function is paid attention as the marker for several cardiovascular events. In catheter ablation for persistent atrial fibrillation (AF), extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram ablation in addition to pulmonary vein isolation (PVI-plus), could impair LA function more severely than PVI-alone strategy. Purpose The aim of this study is to investigate the impact of PVI-plus strategy on LA function and an incidence of cardiovascular events. Methods This study is a post-hoc subanalysis of the EARNEST-PVI randomized controlled trial (NCT03514693), which investigated the efficacy of the PVI-alone strategy in comparison with PVI-plus strategy for persistent AF. From the 497 participants of EARNEST-PVI trial, we enrolled 191 patients with full datasets of pre- and post-ablation cardiac computed tomography (CT). Patients were divided into PVI-alone and PVI-plus groups. Within one month before and 3 months after ablation, LA volume index (LAVI) and LA emptying fraction (LAEF) were calculated. We assessed (i) post-ablation LAEF (LAEFpost), (ii) AF/AT -free rate after final session, and (iii) association between PVI-plus strategy and composite cardiovascular events; all-cause death, embolic stroke, and heart failure (HF) hospitalization. Results The baseline LAVI and LAEF were not different between PVI-alone (N=96) and PVI-plus groups (N=95) [LAVI: 71.4(57.8, 82.0) vs. 68.7(61.0, 78.1), P=0.92, LAEF: 13.7(10.0, 17.4) vs. 13.0(10.0, 16.9), PVI-alone vs. PVI-plus, P=0.78]. In overall patients, LAEFpost did not differ [34.4 (26.1, 40.7) vs. 31.6 (26.0, 37.4), P=0.13]. In the analysis of patients showing sinus rhythm during the CT study, however, LAEFpost was significantly higher in PVI-alone (N=87) than in PVI-plus group (N=93) [35.7(29.0, 41.0) vs. 31.7(26.1, 37.5), P=0.011] (Figure 1). AF/AT-free survival rate after final session during median follow-up of 44 months tended to be higher in PVI-plus (72.9% vs. 84.2%, P=0.053) (Figure 2). The composite cardiovascular events-free rate were not different among two groups (94.8% vs. 96.8%, P=0.42) (Figure 3). LAEFpost was significantly lower in patients with composite events (N=8) than those without (N=183) [18.7(11.5, 28.1) vs. 33.1 (27.0-38.1), P=0.0051]. In multivariate Cox regression model adjusted with age≥75, gender and pre-LAVI, PVI-plus did not show association with composite events (HR: 0.90, 95%CI: 0.18-4.47, P=0.89), while LAEFpost showed strong association (HR:0.88, 95%CI: 0.80-0.96, P=0.0039). Conclusion Compared with PVI-alone strategy, PVI-plus strategy impaired LA function more severely, but tended to have higher ablation success rate, and did not increase cardiovascular events. LAEFpost was independently associated with cardiovascular events. Regardless of ablation strategy, patients with reduced post-ablation LA function should be observed carefully.Post-ablation LA function and recurrenceCardiovascular events and LA function

Echocardiographic predictors of occult atrial fibrillation in patients with cryptogenic stroke

Abstract Background Left atrial (LA) strain has been proposed as an echocardiographic predictor of subsequent atrial fibrillation (AF) in patients presenting with cryptogenic stroke (CS). The purpose of this study was to compare the predictive value of LA strain parameters with traditional echocardiographic measurements for predicting occult AF in patients with CS. Methods We conducted a single-center retrospective cohort study of patients with cryptogenic stroke who underwent implantable cardiac monitor (ICM) placement. Transthoracic echocardiogram (TTE) parameters collected included mitral e and e’ velocities, and LA volume index (LAVI). LA strain was calculated offline using speckle-tracking in apical 4 and 2 chamber views, during the reservoir, conduit, and contractile phases of the cardiac cycle. Strain measurements obtained in each view were averaged (Figure 1). AF episodes had to last at least 2 minutes to qualify as an AF event. Results The cohort consisted of 269 patients with cryptogenic stroke who underwent ICM placement between April 2015 to December 2020, of them 45 patients had AF detected by ICM during follow-up. Echocardiographic evidence of dilated LA measured using LAVI (p=0.043) as well as lower filling pressures measured using e/e’ (p=0.033) were significantly associated with AF. (Table 1). LA function using strain in reservoir, conduit, and contractile phases was not significantly associated with AF (Table 1). Conclusion Increased LA size, but not abnormal LA function was significantly associated with incident AF in patients with CS.

Impaired left atrial reservoir function associated with large v wave in patients with transthyretin amyloid cardiomyopathy

Abstract Background Impaired atrial function, in addition to ventricular diastolic dysfunction, is one of the hallmarks of cardiac amyloidosis (ATTR-CM). Two-dimensional speckle tracking echocardiography is a useful technique for quantitative assessment of LA stiffness. A large v wave on pulmonary artery wedge (PAW) pressure waveform is the findings suggesting LA overload and impaired LA reservoir function. Although large v waves on PAW pressure waveforms are sometimes observed in ATTR-CM patients, their hemodynamic background and clinical significance have not been well described. Purpose To investigate the clinical importance of LA function obtained by echocardiography and PAW pressure waveform and the association of enhanced large PAW v wave to clinical outcomes in ATTR-CM patients. Methods We retrospectively analyzed central hemodynamics in 136 ATTR-CM patients without severe mitral regurgitation. Large v wave was defined 10 mmHg above mean PAW pressure. We divided 136 ATTR-CM into large v wave group (n = 27) and non-large v wave group (n = 109), and compared the differences in baseline parameters and echocardiographic parameters. Results Patients in the large v wave group showed higher mean PAW pressure (24mmHg vs. 14mmHg, p&amp;lt;0.0001). There were no significant differences in age, prevalence of atrial fibrillation, high-sensitivity cardiac troponin T levels (0.060 ng/ml vs. 0.044 ng/mL, p = 0.341), B-type natriuretic peptide levels (188.3 pg/ml vs. 178.7 pg/mL, p = 0.386). In addition, LV ejection fraction, LA diameter, E/e` and cardiac index showed no significant differences between the two groups. However, LA peak longitudinal strain (LS) and LS rate (LSR), evaluation of LA reservoir function, expressed significant depression in large v wave group (LS: 6.24 % vs 9.21 %, p&amp;lt;0.0001, LSR: 0.29 1/s vs 0.38 1/s, p = 0.005). Conclusions In ATTR-CM patients, the impaired LA reservoir function associated with extent of large v wave on PAW pressure. This result suggested that impaired LA function may be useful for assessing the progression of ATTR-CM and the deterioration of central hemodynamics.