Morphology of human sinoatrial node and its surrounding right atrial muscle in the global obesity pandemic-does fat matter?

Introduction: The sinus node (SN) is the main pacemaker site of the heart, located in the upper right atrium at the junction of the superior vena cava and right atrium. The precise morphology of the SN in the human heart remains relatively unclear especially the SN microscopical anatomy in the hearts of aged and obese individuals. In this study, the histology of the SN with surrounding right atrial (RA) muscle was analyzed from young non-obese, aged non-obese, aged obese and young obese individuals. The impacts of aging and obesity on fibrosis, apoptosis and cellular hypertrophy were investigated in the SN and RA. Moreover, the impact of obesity on P wave morphology in ECG was also analyzed to determine the speed and conduction of the impulse generated by the SN. Methods: Human SN/RA specimens were dissected from 23 post-mortem hearts (preserved in 4% formaldehyde solution), under Polish local ethical rules. The SN/RA tissue blocks were embedded in paraffin and histologically stained with Masson's Trichrome. High and low-magnification images were taken, and analysis was done for appropriate statistical tests on Prism (GraphPad, USA). 12-lead ECGs from 14 patients under Polish local ethical rules were obtained. The P wave morphologies from lead II, lead III and lead aVF were analyzed. Results: Compared to the surrounding RA, the SN in all four groups has significantly more connective tissue (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals and young obese individuals) and significantly smaller nodal cells (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals, young obese individuals). In aging, overall, there was a significant increase in fibrosis, apoptosis, and cellular hypertrophy in the SN (P ≤ 0.05) and RA (P ≤ 0.05). Obesity did not further exacerbate fibrosis but caused a further increase in cellular hypertrophy (SN P ≤ 0.05, RA P ≤ 0.05), especially in young obese individuals. However, there was more infiltrating fat within the SN and RA bundles in obesity. Compared to the young non-obese individuals, the young obese individuals showed decreased P wave amplitude and P wave slope in aVF lead. Discussion: Aging and obesity are two risk factors for extensive fibrosis and cellular hypertrophy in SN and RA. Obesity exacerbates the morphological alterations, especially hypertrophy of nodal and atrial myocytes. These morphological alterations might lead to functional alterations and eventually cause cardiovascular diseases, such as SN dysfunction, atrial fibrillation, bradycardia, and heart failure.

Left Atrio-ventricular Coupling Index: A Novel Diastolic Parameter to Refine Prognosis in Heart Failure.

BACKGROUND: Left atrioventricular coupling index (LACI), an index coupling left atrial (LA) to left ventricular (LV) volume at end-diastole, showed to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. The present study aimed to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). METHODS: We retrospectively analyzed 1158 stable HF patients, on optimal medical therapy (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (endpoint: all-cause death/HF-hospitalization) was assessed by Cox regression. Results were validated in an external cohort of 242 HF patients. RESULTS: In the derivation cohort, the median LACI value was 0.29 (IQR:0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. While the prevalence of grade-1 DD (ASE/EACVI classification) progressively decreased across LACI tertiles, the prevalence of grade-3 DD significantly increased (8%,23%, and 46% respectively, P<0.0001). A cut-off value ≥0.26 identified moderate-to-severe DD with an area-under the-curve of 0.75. During follow-up (median 28 months, IQR:11-53), 407 (35%) patients reached the endpoint. On multivariable analysis, LACI was independently associated with outcomes (HR for 1-SD increase 1.16; 95%CI 1.06-1.28; P=0.002), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<0.0001). The prognostic value of LACI was consistent in the external validation cohort. CONCLUSIONS: LACI is associated with DD severity and is an independent predictor of outcomes in HF patients.

Secondary tricuspid regurgitation: incidence, types, and outcomes in atrial fibrillation vs. sinus rhythm.

BACKGROUND AND AIMS: Incidence and types of secondary tricuspid regurgitation (TR) are not well defined in atrial fibrillation (AFib) and sinus rhythm (SR). Atrial secondary TR (A-STR) is associated with pre-existing AFib; however, close to 50% of patients with A-STR do not have AFib. The aim of this study was to assess incidence, types, and outcomes of ≥ moderate TR in AFib vs. SR. METHODS: Adults with and without new-onset AFib without structural heart disease or ≥ moderate TR at baseline were followed for the development of ≥ moderate TR. Tricuspid regurgitation types were pacemaker, left-sided valve disease, left ventricular (LV) dysfunction, pulmonary hypertension (PH), isolated ventricular, and A-STR. RESULTS: Among 1359 patients with AFib and 20 438 in SR, 109 and 378 patients developed ≥ moderate TR, respectively. The individual types of TR occurred more frequently in AFib related to the higher pacemaker implantation rates (1.12 vs. 0.19 per 100 person-years, P < .001), larger right atrial size (median 78 vs. 53 mL, P < .001), and higher pulmonary pressures (median 30 vs. 28 mmHg, P < .001). The most common TR types irrespective of rhythm were LV dysfunction-TR and A-STR. Among patients in SR, those with A-STR were older, predominantly women with more diastolic abnormalities and higher pulmonary pressures. All types of secondary TR were associated with all-cause mortality, highest in PH-TR and LV dysfunction-TR. CONCLUSIONS: New-onset AFib vs. SR conferred a higher risk of the individual TR types related to sequelae of AFib and higher pacemaker implantation rates, although the distribution of TR types was similar. Secondary TR was universally associated with increased mortality.

Anomalous drainage of inferior vena cava into left atrium associated with ostium secundum atrial septal defect: a case report.

Background: Anomalous drainage of inferior vena cava (IVC) into left atrium (LA) is a rare aetiology of cyanosis in adults. This condition may be associated with atrial septal defects, anomalous pulmonary venous drainage, and pulmonary arteriovenous fistulas. This case report presents an instance of anomalous drainage of IVC into LA, associated with ostium secundum atrial septal defect (ASD). It contributes to the existing literature by highlighting the diagnostic challenges associated with this anomaly, particularly during surgical intervention. Case summary: A 38-year-old male presented with a six-year history of exertional dyspnoea and episodic palpitation. Transthoracic echocardiography revealed a large secundum (ASD), the IVC draining into LA, a left superior vena cava, and mild mitral regurgitation. These findings were further confirmed by right and left heart catheterization and CT angiogram. The patient was referred to CTVS department for surgical correction. The post-operative course was uneventful. At a 1.4-year follow-up, the patient reported significant improvement in symptoms. Discussion: We present a case of anomalous drainage of IVC into LA, associated with ostium secundum ASD. An ASD co-occurs with this condition in ∼70% of the reported cases. This anomaly differs from a low or inferior vena caval secundum ASD, where a prominent Eustachian valve can cause blood shunting from the IVC to LA. If the surgeon is not vigilant, this can be mistaken for the inferior ASD rim, potentially leading to iatrogenic diversion of IVC blood to LA upon ASD closure, resulting in cyanosis. This case underscores the diagnostic and surgical challenges associated with this condition.

Porcine lungs perfused with three different flows using the 8-h open-atrium cellular ex vivo lung perfusion technique.

The number of lung transplantations is limited due to the shortage of donor lungs fulfilling the standard criteria. The ex vivo lung perfusion (EVLP) technique provides the ability of re-evaluating and potentially improving and treating marginal donor lungs. Accordingly, the technique has emerged as an essential tool to increase the much-needed donor lung pool. One of the major EVLP protocols, the Lund protocol, characterized by high pulmonary artery flow (100% of cardiac output [CO]), an open atrium, and a cellular perfusate, has demonstrated encouraging short-EVLP duration results. However, the potential of the longer EVLP duration of the protocol is yet to be investigated, a duration which is considered necessary to rescue more marginal donor lungs in future. This study aimed to achieve stable 8-h EVLP using an open-atrium cellular model with three different pulmonary artery flows in addition to determining the most optimal flow in terms of best lung performance, including lung electrolytes and least lung edema formation, perfusate and tissue inflammation, and histopathological changes, using the porcine model. EVLP was performed using a flow of either 40% (n = 6), 80% (n = 6), or 100% (n = 6) of CO. No flow rate demonstrated stable 8-h EVLP. Stable 2-h EVLP was observed in all three groups. Insignificant deterioration was observed in dynamic compliance, peak airway pressure, and oxygenation between the groups. Pulmonary vascular resistance increased significantly in the 40% group (p < .05). Electrolytes demonstrated an insignificant worsening trend with longer EVLP. Interleukin-8 (IL-8) in perfusate and tissue, wet-to-dry weight ratio, and histopathological changes after EVLP were insignificantly time dependent between the groups. This study demonstrated that stable 8-h EVLP was not feasible in an open-atrium cellular model regardless of the flow of 40%, 80%, or 100% of CO. No flow was superior in terms of lung performance, lung electrolytes changes, least lung edema formation, minimal IL-8 expression in perfusate and tissue, and histopathological changes.

Performance and failure of right ventricle to pulmonary artery conduit in congenital heart disease.

INTRODUCTION: Surgical implantation of a right ventricle to pulmonary artery (RV-PA) conduit is an important component of congenital heart disease (CHD) surgery but with limited durability leading to re-intervention. Current single-center, retrospective, cohort study is reporting results of surgically implanted RV-PA conduits in a consecutive series of children and adults with CHD. METHODS: Patients with CHD referred for RV-PA conduits surgical implantation (October 1997 and January 2022) have been included. Primary outcome was conduit failure defined as peak gradient above 64mmHg/severe regurgitation/need for conduit-related interventions. Longitudinal echocardiographic studies were available for mixed-effect linear regression analysis. RESULTS: Two-hundred and fifty-two patients were initially included. One hundred and forty-nine patients were elegible for follow-up data collection. After a median follow-up time of 49 months the primary study endpoint occurred in 44 (29%) patients. Multivariable Cox regression model identified adult age (>18 years) at implantation and pulmonary homograft as protective factors (HR 0.11, 95% CI 0.02-0.47 and HR 0.34, 95% CI 0.16-0.74, respectively). Fever within 7 days of surgical conduit implantation was a risk factor for early (within 24 months) failure (OR 4.29, 95% CI 1.41-13.01). Longterm use of oral anticoagulant was independently associated with slower progression of peak echocardiographic gradient across conduits (mixed effect linear regression p-value 0.027). CONCLUSION: In patients with CHD, surgically implanted RV-PA conduit failure is faster in children and after non-homograft conduit implantation. Early fever after surgery is a strong risk factor for early failure. Longterm anticoagulation seems to exert a protective effect.

Estimate of the hydraulic force in the aging heart: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Coupling between left ventricle (LV) and left atrium (LA) plays a central role in the process of cardiac remodeling during aging and development of cardiac disease. The hydraulic force (HyF) is related to variation in size between LV and LA. The objectives of this study were to: (1) derive an estimate of left atrioventricular HyF using cine- Magnetic Resonance Imaging (MRI) in healthy subjects with a wide age range, and (2) study its relationship with age and conventional diastolic function parameters, as estimated by reference echocardiography. METHODS: We studied 119 healthy volunteers (mean age 44 ± 17 years, 58 women) who underwent Doppler echocardiography and MRI on the same day. Conventional transmitral flow early (E) and late (A) LV filling peak velocities as well as mitral annulus diastolic longitudinal peak velocity (E') were derived from echocardiography. MRI cine SSFP images in longitudinal two and four chamber views were acquired, and analyzed using feature tracking (FT) software. In addition to conventional LV and LA strain measurements, FT-derived LV and LA contours were further used to calculate chamber cross-sectional areas. HyF was approximated as the difference between the LV and LA maximal cross-sectional areas in the diastasis phase corresponding to the lowest LV-LA pressure gradient. Univariate and multivariate analyses while adjusting for appropriate variables were used to study the associations between HyF and age as well as diastolic function and strain indices. RESULTS: HyF decreased significantly with age (R²=0.34, p < 0.0001). In addition, HyF was significantly associated with conventional indices of diastolic function and LA strain: E/A: R²=0.24, p < 0.0001; E': R²=0.24, p < 0.0001; E/E': R²=0.12, p = 0.0004; LA conduit longitudinal strain: R²=0.27, p < 0.0001. In multivariate analysis, associations with E/A (R2 = 0.39, p = 0.03) and LA conduit strain (R2 = 0.37, p = 0.02) remained significant after adjustment for age, sex, and body mass index. CONCLUSIONS: HyF, estimated using FT contours, which are primarily used to quantify LV/LA strain on standard cardiac cine MRI, varied significantly with age in association with subclinical changes in ventricular filling. Its usefulness in cohorts of patients with left heart disease to detect LV-LA uncoupling remains to be evaluated.

Left atrial and ventricular longitudinal strain by cardiac magnetic resonance feature tracking improves prognostic stratification of patients with ST-segment elevation myocardial infarction.

We aimed to investigate the predictive value of left atrium (LA) and left ventricle (LV) longitudinal strain derived by CMR-FT early after ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Patients with STEMI who received pPCI and completed CMR within the following week were enrolled. LA and LV longitudinal strain parameters were derived from cine CMR by FT; conventional CMR indexes were also performed. The primary endpoint was the occurrence of major cardiovascular adverse events (MACE), defined as a composite of death, reinfarction, and congestive heart failure (HF). 276 participants (median age, 57 years, IQR, 48-66 years; 85% men) were included in this study. CMR was usually completed on the 5 (IQR,4-7) days after pPCI. During a median follow-up of 16 months, MACE occurred in 35 (12.7%) participants. Multivariable Cox regression analysis showed that LA conduit strain (HR 0.91, 95%CI: 0.84, 0.98, p = 0.013) and LV global longitudinal strain (HR 1.17, 95%CI: 1.03, 1.34, p = 0.016) remained independently associated with MACE. Participants with impaired LA conduit strain (≤ 12.8%) and LV global longitudinal strain (> -13.1%) had a higher risk of MACE than those with preserved. Longitudinal strain of LA and LV could provide independent prognostic information in STEMI patients, and comprehensive assessment of Left atrial and ventricular longitudinal strain significantly improved the prognosis.

Cardiac Mechanics and the Risk of Atrial Fibrillation in a Community-Based Cohort of Older Adults.

BACKGROUND: Assessment of cardiac structure and function improves risk prediction of new-onset atrial fibrillation (AF) in different populations. We aimed to comprehensively compare standard and newer measures of cardiac structure and function in improving prediction of AF in a cohort of older adults without history of AF and stroke. METHODS: We included 5050 participants without prevalent AF and stroke (mean age 75 ± 5 years, 59% women and 22% Black) from the Atherosclerosis Risk in Communities (ARIC) study who underwent complete 2-dimensional echocardiography, including speckle-tracking analysis of the left ventricle (LV) and left atrium (LA). We assessed the association of cardiac measures with incident AF (including atrial flutter) and quantified the extent to which these measures improved model discrimination and risk classification of AF compared with the CHARGE-AF score. RESULTS: Over a median follow-up time of 7 years, 676 participants developed AF (incidence rate, 2.13 per 100 person-years). LV mass index and wall thickness, E/e' and measures of LA structure and function, but not LV systolic function, were associated with incident AF, after accounting for confounders. Above all, LA reservoir strain, contraction strain, and LA minimal volume index (C-statistics [95%Confidence interval]: 0.73 [0.70,0.75], 0.72 [0.70,0.75] and 0.72 [0.69,0.75], respectively) significantly improved the risk discrimination of the CHARGE-AF score (baseline C-statistic: 0.68 [0.65,0.70]) and achieved the highest category-based net reclassification improvement (29%, 24% and 20%, respectively). CONCLUSIONS: In a large cohort of older adults without prevalent AF and stroke, measures of LA function improved the prediction of AF more than other conventional cardiac measures.

Molecular Pathways and Animal Models of Atrial Septal Defect.

The relative simplicity of the clinical presentation and management of an atrial septal defect belies the complexity of the developmental pathogenesis. Here, we describe the anatomic development of the atrial septum and the venous return to the atrial chambers. Experimental models suggest how mutations and naturally occurring genetic variation could affect developmental steps to cause a defect within the oval fossa, the so-called secundum defect, or other interatrial communications, such as the sinus venosus defect or ostium primum defect.

Clinical Presentation and Therapy of Total Anomalous Pulmonary Venous Return.

Total anomalous pulmonary venous return (TAPVR) is rare (accounting for about 1% of all CHD) and can occur as a single lesion or in combination with other types of CHD (such as heterotaxy or HLHS). TAPVR is defined as an abnormal connection where all pulmonary veins do not drain into the left atrium but into the right atrium either directly or through a vein that is connected to the right atrium. TAPVR can be divided into four anatomic groups (Fig. 32.1): (1) supracardiac (about 55%), (2) cardiac (about 30%), (3) infracardiac (about 13%), and (4) mixed (very rare). In addition, it can be divided into two physiological types: nonobstructed and obstructed. Embryologically, all pulmonary veins usually connect to a pulmonary venous confluence that connects to the left atrium. If this connection does not occur, the pulmonary venous confluence connects to a systemic vein instead.

Chronic mild to moderate mitral regurgitation will not have an impact on left atrial strain parameters in the pediatric population.

BACKGROUND: Left atrial strain (LAS) analysis represents a newer non-invasive, sensitive and specific technique for assessing left atrial (LA) function and early detection of its deformation and dysfunction. However, its applicability in mitral regurgitation (MR) in pediatric population remains unexplored, raising pertinent questions regarding its potential role in evaluating the severity and progression of the disease. OBJECTIVE: To investigate the impact of chronic MR in children and adolescents on LA remodeling and function. METHODS: The study included 100 participants. Patients with primary and secondary chronic MR lasting at least 5 years fit our inclusion criteria. The exclusion criteria from the study were: patients with functional mitral regurgitation due to primary cardiomyopathies, patients with artificial mitral valve, patients with MR who had previously undergone surgery due to obstructive lesions of the left heart (aortic stenosis, coarctation of the aorta), patients with significant atrial rhythm disorders (atrial fibrillation, atrial flutter). The echocardiographic recordings were conducted by two different cardiologists. Outcome data was reported as mean and standard deviation (SD) or median and interquartile range (Q1-Q3). RESULTS: The study included 100 participants, of whom 50 had MR and the remaining 50 were without MR. The average age of all participants was 15.8 ± 1.2 years, with a gender distribution of 37 males and 63 females. There was a significant difference in the values of LA volume index (LAVI), which were higher in patients with MR (p= 0.0001), S/D ratio (and parameters S and D; p= 0.001, p= 0.0001, p= 0.013), mitral annulus radius (p= 0.0001), E/A ratio (p= 0.0001), as well as septal e' (m/s), lateral e' (m/s), and average E/e' ratio, along with the values of TV peak gradient and LV global longitudinal strain (%). There was no significant difference in LA strain parameters, nor in LA stiffness index (LASI). CONCLUSION: Our findings revealed significant differences in several echocardiographic parameters in pediatric patients with MR relative to those without MR, providing insight into the multifaceted cardiac structural and functional effects of MR in this vulnerable population.

Trajectory of Diastolic Function after Heart Transplantation as Assessed by Left Atrial Deformation Analysis.

Diastolic dysfunction (DD) is a prevalent and clinically significant complication after heart transplantation (HTX). We aimed to characterize the diastolic function of HTX recipients with both short-term and long-term follow-ups by applying left atrial (LA) deformation analysis. We consecutively enrolled and followed up with 33 HTX patients. Three assessments were performed one month, 3-5 months, and 3-5 years after surgery. Beyond conventional echocardiographic measurements, apical four-chamber views optimized for speckle tracking analysis were acquired and post-processed by dedicated software solutions (TomTec AutoStrain LA and LV). Left atrial phasic functions were characterized by reservoir, conduit, and contraction strains. We categorized diastolic function according to current guidelines (normal diastolic function, indeterminate, DD). At the first assessment, nine (27%) patients were in the DD category, and eleven (33%) were indeterminate. At the second assessment, only one patient (3%) remained in the DD category and six (18%) were indeterminate. At the third assessment, 100% of patients were categorized as having normal diastolic function. LA reservoir strain gradually increased over time. LA contraction strain significantly improved from the second to the third assessment. We found a correlation between the LA reservoir strain and NT-proBNP (r = 0.40, p < 0.05). DD is prevalent immediately after HTX but rare until the end of the first postoperative quarter. Speckle tracking analysis enables the characterization of LA phasic functions that may reflect both short- and long-term changes in diastolic function and correlate with NT-proBNP.

Change in left atrial function and volume predicts incident heart failure with preserved and reduced ejection fraction: Multi-Ethnic Study of Atherosclerosis.

AIMS: The role of change in left atrial (LA) parameters prior to the onset of heart failure (HF) remains unclear. We used cardiac magnetic resonance (CMR) imaging to investigate the relationship between longitudinal change in LA function and incident HF in a multi-ethnic population with subclinical cardiovascular disease (CVD). METHODS AND RESULTS: In this prospective multi-ethnic cohort study, 2470 participants (60 ± 9 years, 47% males), free at baseline of clinical CVD, had LA volume and function assessed via multimodality tissue tracking on CMR imaging at baseline (2000-02) and a second study 9.4 ± 0.6 years later. Free of HF, 73 participants developed incident HF [HF with preserved ejection fraction (HFpEF), n = 39; reduced ejection fraction (HFrEF), n = 34] 7.1 ± 2.1 years after the second study. An annual decrease of 1 SD unit in peak LA strain (ΔLASmax) was most strongly associated with the risk of HFpEF [subdistribution hazard ratios (HR) = 2.56, 95% confidence interval (CI) (1.34-4.90), P = 0.004] and improved model reclassification and discrimination in predicting HFpEF [C-statistic = 0.84, 95% CI (0.79-0.90); net reclassification index (NRI) = 0.34, P = 0.01; and integrated discrimination index (IDI) = 0.02, P = 0.02], whilst an annual decrease of 1 mL/m2 of pre-atrial indexed LA volumes (ΔLAVipreA) was most strongly associated with the risk of HFrEF [subdistribution HR = 1.88, 95% CI (1.44-2.45), P < 0.001] and improved model reclassification and discrimination in predicting HFrEF [C-statistic = 0.81, 95% CI (0.72-0.90); NRI = 0.31, P = 0.03; and IDI = 0.01, P = 0.50] after adjusting for event-specific risk factors and baseline LA measures. CONCLUSION: ΔLASmax and ΔLAVipreA were associated with and incrementally predictive of HFpEF and HFrEF, after adjusting for risk factors and baseline LA measures in this population of subclinical CVD.

Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Structural, Functional, and Electrical Remodeling of the Atria With Reduced Cardiorespiratory Fitness: Implications for AF.

BACKGROUND: Reduced cardiorespiratory fitness (CRF) is an independent risk factor for the progression of atrial fibrillation (AF). We hypothesized that reduced CRF is associated with structural, functional, and electrical remodeling of the left atrium. OBJECTIVES: This study sought to correlate objectively assessed CRF with functional and electrical left atrial (LA) parameters using invasive and noninvasive assessments. METHODS: Consecutive patients with symptomatic AF undergoing catheter ablation were recruited. CRF was objectively quantified pre-ablation by using cardiopulmonary exercise testing. Using peak oxygen consumption, participants were classified as preserved CRF (>20 mL/kg/min) or reduced CRF (<20 mL/kg/min). LA stiffness was assessed invasively with hemodynamic monitoring and imaging during high-volume LA saline infusion. LA stiffness was calculated as ΔLA diameter/ΔLA pressure over the course of the infusion. LA function was assessed with echocardiographic measures of LA emptying fraction and LA strain. Electrical remodeling was assessed by using high-density electroanatomical maps for LA voltage and conduction. RESULTS: In total, 100 participants were recruited; 43 had reduced CRF and 57 had preserved CRF. Patients with reduced CRF displayed elevated LA stiffness (P = 0.004), reduced LA emptying fraction (P = 0.006), and reduced LA reservoir strain (P < 0.001). Reduced CRF was also associated with reduced LA voltage (P = 0.039) with greater heterogeneity (P = 0.027) and conduction slowing (P = 0.04) with greater conduction heterogeneity (P = 0.02). On multivariable analysis, peak oxygen consumption was independently associated with LA stiffness (P = 0.003) and LA conduction velocities (P = 0.04). CONCLUSIONS: Reduced CRF in patients with AF is independently associated with worse LA disease involving functional and electrical changes. Improving CRF may be a target for restoring LA function in AF.

Inflow Tract Development.

The development of the inflow tract is undoubtedly one of the most complex remodeling events in the formation of the four-chambered heart. It involves the creation of two separate atrial chambers, the formation of an atrial/atrioventricular (AV) septal complex, the incorporation of the caval veins and coronary sinus into the right atrium, and the remodeling events that result in pulmonary venous return draining into the left atrium. In these processes, the atrioventricular mesenchymal complex, consisting of the major atrioventricular (AV) cushions, the mesenchymal cap on the primary atrial septum (pAS), and the dorsal mesenchymal protrusion (DMP), plays a crucial role.

Clinical Presentation and Therapy of Atrioventricular Septal Defect.

Atrioventricular septal defects (AVSDs) consist of a number of cardiac malformations that result from abnormal development of the endocardial cushions. AVSDs occur in 0.19 of 1000 live births and constitute 4-5 % of congenital heart defects. AVSDs can be categorized as incomplete (or partial) or complete, and intermediate or transitional.

Left atrial function in middle-aged men and women with and without paroxysmal atrial fibrillation: Data from the Akershus Cardiac Examination (ACE) 1950 study.

PURPOSE: To assess left atrial (LA) function in individuals with known paroxysmal atrial fibrillation (AF) compared with healthy and nonhealthy individuals without atrial fibrillation. METHODS: The Akershus Cardiac Examination 1950 Study included 3,706 individuals all born in 1950. LA strain assessment of reservoir (LASr), conduit (LAScd) and contractile (LASct) functions were performed in all participants by investigators blinded to clinical data. Participants with cardiovascular disease, obesity, diabetes, pulmonary or renal disease were defined as nonhealthy, and those without as healthy. Patients with paroxysmal AF were identified through medical history and ECG documentation. RESULTS: LA strain assessment was feasible in 3,229 (87%) of the participants (50% women). The healthy group (n = 758) had significantly higher LASr and LAScd than the nonhealthy (n = 2,376), but LASct was similar between the groups. Participants with paroxysmal AF had significantly lower values of all strain parameters than the other groups. Multivariable logistic regression showed a significantly reduced probability of having AF per standard deviation increase in LASr and LASct. A nonlinear restricted cubic spline model fitted better with the association of LASr with paroxysmal AF than the linear model, and LA strain values below the population mean associated with an increased probability of having AF, but for values above the population mean no such association was present. CONCLUSION: Compared to participants without AF, those with known paroxysmal AF had significantly lower values of all LA strain parameters during sinus rhythm. Lower values of LA strain were associated with a significantly increased probability of having AF.