Left Size Research Articles

Factor Analysis of the Missed Diagnosis of Total Anomalous Pulmonary Venous Connection in Prenatal Echocardiography.

This study investigated the major factors contributing to the missed diagnosis of total anomalous pulmonary venous connection (TAPVC) in fetal echocardiography. We retrospectively analyzed the prenatal ultrasonic images of 32 fetuses with missed diagnoses of TAPVC, compared them with autopsy and postnatal surgical records, and summarized the most likely reasons leading to the missed diagnoses. We studied a total of 157 fetuses with TAPVC, 32 (20.3%) of whom were missed in prenatal echocardiography. The main factors for the missed diagnoses of TAPVC in the 32 fetuses were anatomic variants leading to the formation of a false pulmonary venous horn-like structure, the combination of TAPVC with other intracardiac anomalies, difficulty or inability to show the course and abouchement of TAPVC on conventional color Doppler flow imaging (CDFI), and excessive color flow gain, with a rate of approximately 53.1% (17/32). A decreased left atrial size and augmentation of the PLAS index may be indicators of false pulmonary venous horn-like structure. False pulmonary venous horn-like structures due to anatomic variants are a major factor in the missed diagnosis of fetal TAPVC. The presence of pulmonary venous horn-like structure in a four-chamber view does not completely exclude TAPVC.

Progress of echocardiography in the evaluation of left atrial function in patients with heart failure with preserved ejection fraction: a narrative review.

About half of all heart failures are heart failures with preserved ejection fraction (HFpEFs). As the population ages and metabolic disorders become more common, the prevalence of HFpEF continues to increase annually. Patients with HFpEF typically show a decline in various reserve capacities after exercise. According to recent research, patients with HFpEF may have significant clinical symptoms due to left atrial (LA) dysfunction. Patients with HFpEF may benefit greatly from the early detection of LA myocardial damage using echocardiographic measurements, particularly LA strain. This article examined state-of-the-art echocardiography as it relates to the assessment of LA function in patients with HFpEF. Databases such as PubMed, Google Scholar, and Baidu Scholar were searched to retrieve the latest articles on research advances in the field from 1998 to 2024. The article searches were not limited by rigid language or publication date constraints. This article outlines LA strain measurements using echocardiography, and provides the current normal reference range for LA strain values. Further, the features of differences in LA strain during exercise and rest are outlined for HFpEF patients in varying stages of heart failure. Finally, the clinical significance of LA strain in HFpEF is highlighted, including its substantial advantages in diagnosing diastolic dysfunction and left ventricular filling pressures, as well as its diagnostic and prognostic utility and potential as a therapeutic target. When evaluating the structure and function of the left atrium in patients with HFpEF, echocardiography shows a great deal of clinical promise. Specifically, LA strain may provide additional useful information for the early identification of LA dysfunction in HFpEF patients. The measurement of LA size is currently the only clinical test available for evaluating the left atrium in individuals with HFpEF. This review will enable ultrasonographers and physicians to better understand the clinical utility of LA strain in patients with HFpEF, and also provides important resources for future LA strain-related scientific research and clinical practice.

Evaluation of Cardiologic Alterations in Radiographs of Dogs with Bronchopneumonia Before and After Treatment

Pneumonia, a common respiratory disease in small animals, causes significant hypoxemia in dogs due to reduced lung capacity and cardiac output. In addition, pneumonia may lead to cardiac complications. This study aimed to evaluate the alterations in cardiac silhouette and main vessel views in dogs that underwent bronchopneumonia treatment, and the alterations were evaluated in radiographs of the dogs with bronchopneumonia before and after treatment. For this purpose, radiographic data from 26 dogs diagnosed with and treated for bronchopneumonia were analyzed. The measurements included left atrial size, long axis, short axis, the fourth thoracic vertebra length, aorta width, caudal vena cava width, and thoracic width. Radiographs obtained before and after treatment indicated no changes in the long and short axes of the vertebral hearth score, the fourth thoracic vertebrae length, aorta and caudal vena cava width, and thoracic width. However, in pre-treatment radiographs, the left atrial size was found to be larger compared to post-treatment radiographs. A strong positive correlation was observed between measurements of LAs and LAs/TV4 in both pre- and post-treatment radiographs, as well as in the measurement differences between pre- and post-treatment radiographs. As a consequence, the radiographs employed to monitor bronchopneumonia treatment may serve as an initial indicator of potential cardiac complications in affected dogs.

Left Atrial Size and Strain in Hypertensive Children Compared to Age-, Sex-, and Race/Ethnicity-Matched Controls.

Left atrial (LA) volume and peak longitudinal strain (LA strain) are indicators of left ventricular (LV) diastolic function in adults, but little is known about LA volume and strain in pediatric patients with hypertension (HTN). We evaluated LA volume and strain in pediatric cases with HTN compared to age-, sex-, and race/ethnicity-matched controls. This was a retrospective matched case-control study of patients who presented to the HTN clinic at CHOP from 12/2011 to 9/2018. Coarctation of the aorta, cardiomyopathy or heart transplantation cases were excluded. HTN was defined by an abnormal ambulatory blood pressure result. LA volume was measured by biplane area-length method and indexed to body surface area (BSA). LA strain and strain rate were measured using TOMTEC® software. Left ventricular mass index (LVMI) was measured by M-mode and the 5/6 area-length method indexed to height2.7. LV global longitudinal strain (LV GLS) was measured during the echocardiographic examination on the GE ultrasound machine for cases and offline using TOMTEC® software for controls. Measurements were compared using Chi-square, McNemar, or Wilcoxon signed rank tests. We included 47 cases and 47 controls. There was no difference in LA volume z-scores (-1.9 vs. -0.9, p = 0.068), LA strain (37.8% vs. 38.0%, p = 0.735) or LA strain rate (1.4 vs. 1.5, p = 0.852) in cases compared to controls. LVMI by M-mode and 5/6 area-length method was higher in cases compared to controls (40.0 vs. 33.7g/m2.7, p < 0.001 and 29.9 vs 24.4g/m2.7, p = < 0.001, respectively). LV GLS was decreased (less negative) in cases compared to controls. In summary there was no difference in LA volume or LA strain in cases compared to controls. In cases, LVMI was significantly elevated and LV GLS was significantly decreased, which may be the first response to HTN, prior to affecting LA size.

Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS.

Coagulation factor XI (FXI) inhibitors are a promising and novel class of anticoagulants, but a recent animal study found that FXI inhibition exacerbated diastolic dysfunction and heart failure (HF). In the ARIC study (Atherosclerosis Risk in Communities), we investigated whether plasma FXI level was associated with cardiovascular events and cardiac function. ARIC was our primary analytic cohort. We included 4471 participants (median age, 75 years; 57% female; 17% Black) who attended visit 5 (2011-2013) with Somalogic-quantified plasma FXI levels and echocardiographic cardiac function. Prevalent HF and atrial fibrillation (AF) cases were defined as having HF or AF diagnosed at or before each participant's visit 5 exam date. Incident HF and AF events were ascertained through 2021. Associations were assessed using Cox, logistic, and linear regression models. Primary prospective associations were also validated in the CHS (Cardiovascular Health Study) using an orthogonal FXI assay (enzyme-linked immunosorbent assay). At ARIC visit 5, there were 665 and 419 participants with prevalent HF and AF, respectively. During a median follow-up of 9 years, there were 580 and 788 incident HF and AF events, respectively. Lower FXI level was associated prospectively with higher incidence of HF (hazard ratio [HR], 1.36 [for each 1-unit decrement of log2-transformed FXI level] [95% CI, 1.01-1.83]) but not incident AF, and cross-sectionally with increased odds of AF (odds ratio [OR], 1.96 [95% CI, 1.23-3.07]) but not HF. In age-stratified analyses, decreased FXI was associated with higher incidence of HF in participants ≥75 years of age (HR, 1.57 [95% CI, 1.08-2.28]) but not <75 years of age (HR, 1.11 [95% CI, 0.68-1.79]). The inverse FXI-HF association was validated in CHS (HR, 1.18 [95% CI, 1.02-1.36]). At ARIC visit 5, lower FXI level was also associated with higher prevalence of diastolic dysfunction and worse E/A ratio, left atrial (LA) volume index, LA function, and left ventricular mass index, but not left ventricular ejection fraction or global longitudinal strain. Decreased FXI level is associated with greater incidence of HF, especially in older adults. It is also associated with prevalent AF, worse diastolic function, worse LA function, and greater LA size. More research is needed to assess potential unwanted effects of FXI inhibition on the risk of cardiovascular events and cardiac function.

Abstract 4117365: Effect Of Renal Denervation In Combination With Cardiac Ablation On The Recurrence Of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Background: Atrial fibrillation(AF) is the most common cardiac arrhythmia, affecting millions globally. Despite various treatments, recurrence remains high, especially among those with drug-resistant hypertension. Aim: To evaluate the efficacy of combining Renal Denervation and Cardiac Ablation compared to Cardiac Ablation Alone in reducing AF recurrence. Methods: A systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines, A search for randomized controlled clinical trials was carried out in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ScienceDirect until March 2024. Specifically, about adult patients aged 18 years and above diagnosed with AF and drug-resistant hypertension undergoing renal denervation and or cardiac ablation. The primary outcome was the recurrence of AF. The secondary outcomes were effects on systolic blood pressure, diastolic blood pressure, cardiovascular structural changes, glomerular filtration rate (eGFR). In addition, periprocedural events and major complication events. Dichotomous outcomes were calculated using relative risk (RR) with 95% confidence interval (CI). For continuous variables, the results were shown considering the mean difference (MD) and standard deviation with 95% CI. Results: From 409 studies identified, 8 studies and 695 patients were included. Meta-analysis showed a significant reduction in atrial fibrillation recurrence with the combination therapy (HR 0.66 [95% CI=0.55 – 0.79], p=0.00001). Blood pressure outcomes were superior in the combination group, with reductions in both systolic (MD = -9.66 mmHg [95% CI: -13.89, -5.42], p=0.00001) and diastolic pressures (MD = -7.09 mmHg [95% CI: -13.67, -0.50], p=0.003). Cardiovascular structural changes, such as left atrial size (RR 2.85 [95% CI: 2.13, 3.81], p=0.00001) and interventricular septal thickness (MD = -1.15 [95% CI: -1.85, -0.44], p=0.003), also favored the combination therapy. Kidney function, measured by eGFR was better preserved (MD = -10.34 [95% CI: -13.39, -7.28], p&lt;0.00001). Conclusion: The combination of RDN and CA is more effective than CA alone in reducing the recurrence of AF, with additional benefits in blood pressure control, cardiovascular structural improvements, and renal function preservation.

Abstract 4137726: A Deep Learning Digital Biomarker for Mitral Valve Prolapse using Echocardiogram Videos

Background: Mitral valve prolapse (MVP) has a prevalence of 2–3% and is a risk factor for heart failure and sudden death, but MVP diagnosis by transthoracic echocardiography (TTE) requires time and clinical expertise. We trained a deep learning model to classify MVP from TTE videos. Methods: DROID-MVP is a convolutional neural network trained to classify MVP using echocardiographer labels using 973,531 digital videos (parasternal long axis and apical views) from 45,657 studies performed in 15,728 cardiology patients at Massachusetts General Hospital. We validated DROID-MVP in 1,726 cardiology patients (4,869 studies) and 8,903 primary care patients (8,903 studies), and tested associations between predicted MVP score (range 0-1) and mitral regurgitation (MR) severity and left atrial (LA) anterior-posterior diameter in primary care patients with available measurements. Results: Of 15,728 patients (6,029 [38%] women; mean age at first TTE 61 ± 17 years) in the training set, 729 (4.6%) had at least 1 study with MVP. DROID-MVP identified MVP in both the cardiology (area under the receiver operating characteristic curve [AUC] 0.955 [95% confidence interval: 0.939-0.970]; average precision [AP] 0.716 [0.649-0.776]; prevalence 0.035) and primary care (AUC 0.966 [0.955-0.978]; AP 0.668 [0.601-0.730]; prevalence 0.022) test sets ( Figure 1 ). Discrimination persisted across strata of MR severity (AUC range 0.877-0.987). High (&gt;0.67) vs low (&lt;0.33) MVP score was associated with higher odds of moderate/severe MR (odds ratio 20.1 [12.2-33.4], p&lt;0.001) and higher LA diameter (2.7 [0.9-4.4] mm, p&lt;0.001; Figure 2 ), after adjusting for age, sex, height, and weight. Conclusions: A deep learning model identifies MVP from TTE videos with excellent discrimination and higher model predictions are associated with greater MR severity and LA size. Our work demonstrates how deep learning can automate MVP diagnosis and may serve as a digital biomarker of MVP-associated structural abnormalities.

Abstract 4135307: Integrating genomics and proteomics to identify causal proteins and biologic pathways for incident atrial fibrillation in chronic kidney disease

Introduction/ Background: Individuals with chronic kidney disease (CKD) are at an increased risk for developing atrial fibrillation (AF). Research Objective: By integrating genomics and proteomics, we sought to identify proteins and biologic pathways causally linked to the development of AF in the CKD population. Methods / Approach: We measured 4638 unique plasma proteins using SomaScan v.4.0 in participants (ppts) with CKD and no prior AF from 2 cohorts: Chronic Renal Insufficiency Cohort (CRIC, n=2654) and Atherosclerosis Risk in Communities Cohort (ARIC, n=1326). Associations of individual proteins with incident AF were analyzed using Cox regression after adjustment for demographics, comorbidities, and kidney function. Among proteins independently associated with incident AF in both cohorts, we tested for causality using two-sample Mendelian Randomization (MR). Previously published genome wide association studies (GWAS) were used to identify both protein quantitative loci (cis-pQTL) and summary statistics for incident AF. We then used Ingenuity Pathway Analysis to compare proteins and pathways associated with both incident AF and an increase in left atrial (LA) size across serial echocardiograms in CRIC. Results / Data: Over the 5-year analytic period, incident AF occurred in 150 ppts from CRIC and 140 ppts from ARIC. Eight proteins were independently associated with AF in both cohorts: NT-proBNP, SVEP1, TAGLN, TFF3, WAP4, MMP-12, CILP2 and NELL-1. Of these, 3 were significant in MR analysis (Figure 1): CILP2 and MMP-12 maintain structural integrity of the extracellular matrix in the heart and modulate the fibrotic response; NELL-1 is responsible for cell signaling in kidney disease and cardiovascular development. In addition, leading biologic pathways implicated in both development of AF and increase in LA size included systemic fibrosis (p=1.7x10 -4 for AF and 2.3 x10 -4 for LA); regulation of insulin-like growth factor (p=2.3 x10 -4 for AF and p=4.3 x10 -7 for LA) and extracellular matrix degradation (p=5.5 x10 -4 for AF and p=4.2 x10 -4 for LA). Conclusions: Trans-omics analyses identified 3 proteins causally associated with developing AF in the CKD population. Also, several pathways involved with cardiac remodeling and fibrosis are common to the development of AF and LA remodeling.

Approaches to rhythm control: Impact of electrical cardioversion versus pharmacological management on left atrial size and systolic performance in atrial fibrillation and flutter

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To compare the impact of electrical cardioversion (ECV) and pharmacological cardioversion (PCV) on left atrial size (LA) and left ventricular ejection fraction (LVEF), as well as to identify predictors of rhythm disorder recurrence in patients with atrial fibrillation (AF) or atrial flutter (AFL).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; A prospective observational cohort study was conducted on 105 patients with persistent AF or AFL at the University Clinical Centre Tuzla. The patients were divided into two groups: 53 underwent ECV and 52 received PCV. Demographic and clinical data, including ECG and transthoracic echocardiography, were collected. Follow-up assessments were conducted at 7 days, 1 month, and subsequently every 3 months for a year.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; Baseline characteristics were similar between the groups. Recurrence of rhythm disorder within one year was observed in 52.4% of cases, with ECV showing a slightly lower, though not significantly different, primary failure rate at 7 days compared to PCV (13.2% vs. 23.1%). Significant predictors of recurrence included longer duration of disorder (p&amp;amp;lt;0.001), hypertension (p=0.016), lack of pre-cardioversion amiodarone (p=0.027), and larger LA (p&amp;amp;lt;0.001). Both ECV and PCV significantly reduced LA over time, with no significant differences in LVEF between groups.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; Both ECV and PCV are effective in restoring sinus rhythm, with a trend towards lower recurrence in the ECV group. Predictors such as disorder duration, hypertension, lack of pre-cardioversion amiodarone, and LA should be considered when planning cardioversion to optimize patient outcomes.&amp;lt;/p&amp;gt;

Prediction of mortality, future arrhythmia and cardiovascular disease: an artificial intelligence-enhanced electrocardiography platform

Abstract Background Artificial intelligence-enhanced electrocardiography (AI-ECG) can be used to identify existing disease, but could additionally be used to predict occurrence of future disease and death. Purpose We developed an AI-ECG platform that predicts mortality and a wide spectrum of future arrhythmia and cardiovascular disease. Methods The AI-ECG risk estimation platform (AIRE) was developed in a dataset of 1,163,401 ECGs from 189,539 patients from a secondary care setting in the USA. Uniquely, AIRE uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves (Fig 1A). AIRE was fine-tuned to additionally predict the endpoints described below. Results AIRE accurately predicts risk of all-cause mortality (C-index 0.775 (0.773-0.776) and can differentiate prognosis in high- and low-risk subjects, even when only cardiologist-defined normal ECGs are considered (Fig 2B). Additionally, in Cox regression analyses, AIRE was superior to conventional risk factors (Fig 1B). AIRE accurately predicted future ventricular arrhythmia (c-index 0.760 (0.756-0.763)), future complete heart block (CHB) (0.809 (0.805-0.814), future atrial fibrillation (0.753 (0.751-0.756), future atherosclerotic cardiovascular disease (0.696 (0.694-0.698)) and future heart failure (0.787 (0.785-0.789)) . AIRE was superior to left ventricular ejection fraction (LVEF) in predicting risk of future ventricular arrhythmias in subjects with LVEF &amp;lt;50% (C-index 0.649 (0.638 – 0.660) vs 0.615 (0.603 – 0.626) p &amp;lt; 0.0001 ). For CHB prediction, AIRE was able to further risk stratify subjects with bifascicular block and syncope into low (1.9% 5 year CHB), intermediate (8.8%), and high risk (20.7%) groups, and could guide treatment decisions. We externally validated our findings in four diverse, transnational cohorts from Brazil and the UK, including volunteers, primary care subjects and patients with Chagas disease, and found AIRE accurately predicted all-cause mortality in all four external cohorts (Fig 2). Non-mortality endpoints were successful externally validated in the UKB. In explainability analyses, we found features of QRS morphology, low QRS voltage, poor precordial R wave progression, inverted and biphasic T waves and ST segment changes were the most significant morphological features associated with high predicted mortality (Fig 1D). Through phenome- and genome-wide association studies (GWAS), we identified candidate biological pathways including changes in cardiac structure (LV mass, LV trabeculation and left atrial size). GWAS identified variants adjacent to VGLL2, KCNQ1, CCDC91 and TBX3 which have been described in association with QT interval, biological aging and metabolic syndrome (Fig 1E). Conclusion AIRE could be used worldwide across a range of clinical contexts for risk estimation of not only mortality but a wide spectrum of future arrhythmia and cardiovascular diseases.Figure 1Figure 2

Evolution over time of cardiac biomarkers, electrocardiographic and echocardiographic features in a large cohort of patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis

Abstract Introduction Data on evolution of transthyretin wild-type cardiac amyloidosis (ATTRwt) during treatment with tafamidis is scarce. This hinders the quest for parameters of response and a priori treatment eligibility. Purpose To study the evolution of biomarkers, ECG, and echocardiographic features during early tafamidis treatment. Methods We prospectively collected data after 12-18 months of treatment in a single-centre database. Changes of NT-proBNP and high-sensitivity Troponin I (hs-cTnI) between baseline and follow-up evaluations (at 12 and 18 months) were tested for significance. For ECG and echocardiographic features, we considered baseline and the last available follow-up (median interval 11.1 months). Results We included 253 patients (median age 77[71-82]years; 90% males). Median (IQR) baseline NT-proBNP was 2472(1355-4749)ng/L, hs-cTnI 47(30-82)ng/L. Furosemide was administered in 58% of cases (median dose 25[25-50]mg/day). Compared to baseline, NT-proBNP was 2342(1316-4148)ng/L at 12 (p=0.886), and 2633(1393-6063)ng/L at 18 months (p=0.285), with 4% and 30% of patients showing ≥30% and ≥300ng/L increase at 12 and 18 months, respectively; hs-cTnI was 46(29-70)ng/L at 12 (p=0.947), and 44(25-68)ng/L at 18 months (p=0.866), with 35% and 7% showing a ≥20% increase at 12 and 18 months, respectively, and 21 (11.5% over 183 analyzable) with increase at 12 and reduction at 18 months. Patients on furosemide were 69% and 70% at 12 and 18 months, respectively; the dose increased to 37.5(25-75)mg/day at 18 months (p=0.009). At baseline, 117(47%) patients had history/permanent atrial fibrillation (AF). Forty-one(16%) had an implantable electronic device, 16(6%) underwent subsequent implantation. Median PR interval was 210(185-240)msec, trending toward prolongation (p=0.054). QRS duration increased (100[86-130]vs120[90-140]msec, p=0.004), together with conduction disturbances (left anterior fascicular block 30[21%]vs43[29%], p=0.036; right bundle branch block 14[10%]vs27[18%], p=0.002). AF prevalence raised from 19% to 25%. There were no significant changes in left ventricular (LV) geometry (septum thickness 18[16-20]vs18[16-20]mm, p=0.666; end-diastolic diameter 45±7vs45±8mm, p=0.434), systolic function (ejection fraction 51±10%vs49±11%, p=0.070), filling pressures (E/e’ 17[11-20]vs14.9[13-19], p=0.086) and left atrial size (mean volume 46±15vs48±13ml/m2, p=0.649). Tricuspid annular plane systolic excursion (18±4vs17±4mm) and pulmonary artery systolic pressure (40[33-45]vs36[30-45]mmHg) remained stable. Conclusions We did not observe neither improvement nor worsening of laboratory/instrumental variables within the first 12-18 months of tafamidis. There was a progression of electrical disorders. After initial progression hs-cTnI tended to improve. Extended follow-up and a matched case-control series will help identify possible later changes useful to monitor treatment response and effects of supporting heart failure treatments.

Gender differences in the evolution of echocardiographic HFpEF characteristics through age deciles: is menopause an inflection point?

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is more prevalent with advancing age and in females. Since sex hormones have trophic effects, menopause may be an inflection point in HFpEF gender characteristics. Aim To compare left ventricular (LV) echocardiographic parameters between gender, through age deciles. Methods A sequential "normal" outpatient cohort in sinus rhythm with Ejection Fraction (EF) &amp;gt;50%, ≤ mild valvular dysfunction, normal chamber sizes and tricuspid regurgitation (TR) gradient &amp;lt;39mmHg were included. Analysis was performed by Kruskal-Wallis and Mann-Whitney U tests. Results are median (quartiles) and p-values of &amp;lt;0.05 were considered significant. Results In 634 patients (65% females), EF tended be larger in females from the fifties decile; females EF 62% (59,65) versus males 60 (56,64) p= 0.013, sixties 62 (58,66) versus 61 (58,64), p=0.07, seventies 63 (59,67) versus 60 (55,64) p=0.009. Mitral inflow characteristics of HFpEF (E:A decreased and E;e’ increased) and TR gradient (increased) progressively evolved throughout the deciles, with no apparent gender difference (males and females all p&amp;lt;0.001). However, while body surface area (BSA) normalised LV diastolic diameters decreased in males (p&amp;lt;0.05) and females (p&amp;lt;0.01), LV systolic diameter (decrease, p&amp;lt;0.01) and left atrial size (increase, p&amp;lt;0.01) only changed in females. Conclusions Whilst age progressively alters hemodynamic echocardiographic characteristics of LV diastolic dysfunction in both sexes, females demonstrate larger LVEF from the fifties decade and left sided structural changes (smaller LV systolic diameter and larger left atrial size) not seen in males. This chronology supports a potential role of loss of sex hormones in HFpEF aetiology.

Left atrial enlargement: a crucial indicator for identifying atrial fibrillation in patients with hypertension

Abstract Background Left atrial enlargement resulting from hypertension is closely linked to the development and persistence of atrial fibrillation (AF). The newly proposed staging recognizes AF as disease continuum, which makes us aware that AF prevention should focus on the Pre-AF stage, and atrial enlargement is one of the important manifestations in this stage. Previous scoring systems, such as CHA2DS2-VASc and C2HEST, along with the recently highlighted left atrial diameter (LAD), have been significant tools for predicting AF occurrence. However, a comprehensive assessment of their utility is currently lacking. Purpose This study aims to explore the role of left atrial size in identifying atrial fibrillation (AF) among hospitalized hypertensives, and to compare its recognition effectiveness with previous scoring systems. Methods We conducted a cross-sectional analysis within hospitalized hypertensives. The discovery, internal and external validation datasets were established. The XGBoost was employed to identify key variables related to AF occurrence, which were ranked based on their importance scores. To gauge the predictive prowess of LAD regarding AF occurrence, we plotted the receiver operating characteristic curve (ROC) and calculated the area under the curve (AUC). This enabled us to pinpoint the LAD cutoff value corresponding to the maximum Youden index, indicative of susceptibility to AF. Subsequently, Youden index determined the optimal cutoff value from the ROC curve. Delong’s test compared the identification abilities of different tools within the same dataset. Logistic regression analysis assessed the correlation between clinical variables and left atrial size. Results The XGBoost revealed 17 variables affecting AF occurrence in hypertensives, with LAD, age, and HF ranking among the top 3 (Figure 2a). LAD had a more pronounced impact on AF occurrence than other variables. LAD-based identification of AF in hypertensives had AUC of 0.827 (95%CI: 0.816-0.837), with an optimal cutoff of 38mm. Subgrouping the study population by LAD≥38mm, ROC curves showed AUCs of 0.757 (95%CI: 0.745-0.768) for the discovery set, 0.750 (95%CI: 0.731-0.768) for internal validation, and 0.759 (95%CI: 0.743-0.776) for external validation. LAD≥38mm had a more higher and stable AUC value for judging the AF occurrence than CHA2DS2-VASc and C2HEST scores (Figure 2b). Hypertensives with LAD≥38mm had a 9.72-fold higher AF risk than those with LAD&amp;lt;38mm. Conclusion LAD is a pivot determinant for AF occurrence. LAD≥38mm is a valuable identifier for high-risk hypertensives prone to AF.Figure 1.Center illustrationFigure 2.XGboost and Delong’s test of ROC

Sex differences in paediatric onset hypertrophic cardiomyopathy

Abstract Background Hypertrophic Cardiomyopathy (HCM) is a heterogeneous disease characterised by age related incomplete penetrance and variable long term outcomes. Sex differences have been described in both the clinical phenotype and natural history of adults with the disease, which have been attributed to both biological (eg sex hormone effect) and non-biological (eg societal and cultural effects) factors. It is unknown if similar sex differences exist in childhood-onset HCM. Purpose This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. Methods Retrospective cohort study from an international registry of patients diagnosed under the age of 18 years with HCM. Patients with syndromic disease (RASopathy syndromes, inborn errors of metabolism, neuromuscular disease) were excluded. Sex differences in baseline characteristics and clinical outcomes were described. Primary outcomes were all-cause mortality or cardiac transplantation, Major Arrhythmic Cardiac Event (MACE) and heart failure event (defined as heart failure death or cardiac transplantation) Results Of 1262 patients, 851 (67.4%) were male (median age 11 yrs (IQR 7.4, 14.4) vs 11.1 (IQR 6.9, 14.0) in females, p=0.0312). Female patients were more likely to have a sarcomeric variant identified (n=208, 85.6% vs 388 (79.4%), p=0.041) despite equivalent genetic testing utilisation between sexes. Female patients were more likely to have severe heart failure symptoms (NYHA 3 or 4) (n=19, 6.1% vs n=20, 2.5% p value 0.030) but there was no difference in the proportion on medical therapy (male n=328, 39.7%, female n=167, 41.8, p value 0.476). The clinical phenotype in terms of degree of hypertrophy, left atrial size and left ventricular outflow tract gradient did not differ by sex. Over a median follow up of 5.2 years (IQR 2.4, 9.9) all-cause mortality or cardiac transplantation did not vary by sex but females were more likely to experience a heart failure event (females 0.6/100,000 pt years (95% CI 0.39-0.92) vs males 0.32/100,000 pt years (95% CI 0.21 – 0.50), hazard ratio 1.89, p value 0.0467). The incidence of MACE did not differ by sex but there was a trend towards higher implantable cardioverter defibrillator implantation in females (n=123, 30.7% vs n=210, 25.4%, p value 0.051). Conclusions For the first time, this study has shown sex differences in paediatric-onset hypertrophic cardiomyopathy. Despite no difference in baseline clinical phenotype, young female patients are more likely to experience heart failure symptoms and heart failure events over follow up. Further studies are required to explore the underlying mechanisms for these observed differences.Table summarising outcomes by sexSurvival free from heart failure

The prognostic and incremental value of T1 mapping for predicting adverse events in hypertrophic cardiomyopathy

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), the prognostic value of native T1 and extracellular volume fraction (ECV) for adverse cardiovascular events has not been well defined. Methods Consecutive 663 participants with HCM who underwent cardiovascular magnetic resonance (CMR) were recruited. The follow-up endpoints included heart failure (HF)-related death and sudden cardiac death (SCD) or aborted SCD. Results During the median follow-up time of 44 months (interquartile range [IQR]: 23 to 66.0 months), 56 (8.4%) participants reached composite endpoints including 38 (5.7%) with SCD or aborted SCD, 16 (2.4%) with HF-related death and 2 (0.3%) with heart transplantation. On multivariable Cox proportional hazards regression analyses, native T1 including late gadolinium enhancement (LGE) from three short axes were significantly associated with cardiac death (basal native T1: hazard ratio [HR], 1.06 per 10 ms increase; 95% confidence interval [CI], 1.02 to 1.09; middle native T1: HR, 1.05 per 10 ms increase; 95% CI, 1.01 to 1.09; apical native T1: HR, 1.04 per 10 ms increase; 95% CI, 1.02 to 1.07; all P &amp;lt; 0.05) after adjustment for non-sustained ventricular tachycardia, history of syncope, the extent of LGE, left atrial size, and NYHA class. Conversely, only basal ECV was associated with cardiac death (basal ECV including LGE area: HR, 1.08 per 1% increase, 95%CI, 1.03 to 1.13, P = 0.001; basal ECV excluding LGE: HR, 1.1 per 1% increase; 95%CI, 1.04 to 1.16; P &amp;lt; 0.001) In addition, participants with increased mean native T1 (≥1349.4 ms) or basal ECV(≥ 29.4%) were more likely to suffer from cardiac death in the entire study cohort or the subgroup with low LGE extent (&amp;lt;15%) or low ESC risk score (&amp;lt;6%) (all P &amp;lt; 0.05). Furthermore, the addition of mean LV native T1 (≥1349.4 ms) or basal ECV (≥ 29.4%) to current risk factors in the guidelines could further improve prediction for the composite endpoint (C-index increased to 0.719 from 0.521 for the AHA/ACC risk model, P &amp;lt; 0.001; C index increased to 0.709 from 0.514 for the ESC risk model; P &amp;lt; 0.001). Conclusions In this study of patients with HCM, mean native T1 of three short axes and basal ECV were independently associated with cardiac death and added incremental value to conventional clinical predictors for patients with HCM.Figure 1.Demonstrative images.Figure 2 Incremental Value of T1 mapping

Speckle tracking echocardiography for evaluation of myocardial functions before and after mitral valvuloplasty in dogs.

Myxomatous mitral valve disease (MMVD) is the most common acquired heart disease in dogs. Mitral valvuloplasty (MVP) addresses regurgitation, but the pre- and postoperative changes in myocardial function remain uncertain. This study evaluated myocardial motion before and after MVP using two-dimensional speckle-tracking echocardiography (2D-STE). Eight client-owned dogs undergoing MVP for MMVD. Myocardial deformation was assessed by 2D-STE before surgery and at 1- and 3-months post-surgery. Measurements included left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), cardiac twist, and right ventricular free wall GLS (RVFW-GLS). Postoperative decreases were observed in left ventricular internal dimensions, left atrial size, and early diastolic myocardial velocity, with an increase in peak late diastolic velocity. LV-GLS decreased at 1 month (-14.4%) and 3 months (-16.3%) compared to preoperative values (-24.4%) (p = 0.0078, p = 0.015). GCS decreased at 1 month (-12.9%) and 3 months (-14.8%) compared to preoperative values (-21.7%) (p = 0.0078). GRS decreased at 1 month (27.7%) and 3 months (32.0%) compared to preoperative values (67.7%) (p = 0.0078). No significant changes were observed in RVFW-GLS. Peak systolic twist increased at 3 months (9.1° vs. 4.9°, p = 0.039). Peak systolic apical rotation showed an upward trend at 3 months (p = 0.109). Left ventricular twist was mildly affected by LVIDd, LVIDDN, and sphericity index (R 2 = 0.187, p = 0.034; R 2 = 0.33, p = 0.0029; R 2 = 0.22, p = 0.019). Postoperative myocardial motion approached reference values, indicating significant improvement, particularly in left ventricular twisting motion. These findings highlight the positive impact of surgery on cardiac function in dogs with MMVD.

Association of serum testosterone levels with left atrial size, function, and risk of atrial fibrillation in adult men: observational and mendelian randomization analyses

Abstract Background Numerous studies have investigated the association between serum testosterone levels, testosterone replacement therapy (TRT), and cardiovascular risk. However, research examining the relationship between testosterone levels and atrial fibrillation (AF) risk remains limited. We comprehensively analyzed the association between total testosterone (TT) levels, intermediary phenotypes such as left atrium (LA) size and function, and the risk of AF in middle-aged and older men. Methods We utilized data from the UK Biobank, a population-based prospective cohort, focusing on 179,988 White men who had complete serum TT level data and no AF history. Observational associations between TT levels and LA imaging traits, as well as AF risk, were estimated using multivariable regression and time-dependent Cox regression models, treating TT levels as a time-varying variable. Genetic associations were examined by Mendelian randomization (MR), using both UK Biobank and external large consortia genome-wide association study data. Results During the median follow-up of 11.8 years (IQR 10.9–12.5), we observed 13,847 incident AF cases (7.7%). Participants with normal TT levels (≥ 300 ng/dL) showed a 15% reduced risk of AF (HR of 0.85 [95% CI, 0.82–0.89]) compared to those with low TT (&amp;lt; 300 ng/dL). Interestingly, participants undergoing TRT experienced a 51% higher risk of AF (1.51 [1.09–2.07]). Furthermore, each 1-standard deviation increase in TT levels was associated with a reduced AF risk (OR of 0.91 [0.89–0.93]) and an improved LA emptying fraction (1.29 [1.06–1.58]). Applying age-specific cutoff values for low TT levels highlighted a more pronounced AF risk reduction in participants with normal TT. MR analyses supported these observations, suggesting potential causal relationships between TT levels and both LA function and AF risk. Conclusions Our findings suggest that low TT levels are associated with reduced LA function and increased risk of AF, both observationally and genetically, indicating that serum TT could serve as a surrogate marker or even a potential causal mediator in the development of AF.Abstract tableAbstract figure

Predictive value of total atrial conduction time for developing cerebrovascular stroke in patients with sinus rhythm and normal left ventricular systolic function, a case-control study

Abstract Background Stroke is the second leading cause of death worldwide. Recently, atrial cardiopathy has become recognized as a substantial risk factor for cerebrovascular stroke. Greater LA size is linked to stroke in AF patients, but few data linking LA size to stroke in population with sinus rhythm. Purpose To investigate the value of total atrial conduction time (TACT) measured non-invasively by assessing PA-TDI duration as a predictor of stroke in patients who initially presented with sinus rhythm and have normal LV systolic function. Methods In our case-control study, we included 156 patients with acute ischemic stroke and 50 control subjects all presented in sinus rhythm and normal LV systolic function. All participants underwent echocardiography. The bi-plane modified Simpson's approach was used to determine the LV-EF. The left atrial (LA) diameter was measured also left atrial volume index (LAVI) was assessed. The PA-TDI interval was used to estimate the TACT. In the apical four-chamber view, the pulsed-wave tissue Doppler sample was positioned on the lateral and septal walls of the LA above the mitral annulus. The time between the onset of the P wave (lead II) and the peak of the A' wave was called the PA-TDI interval. Also, speckle tracking indices of LA strain were measured. Results LA volume index was larger in the stroke group (39.24±4 versus 33.6±2.8, p: 0.01), PA-TDI duration showed statistical highly significant difference between both groups (165.94±21.695 versus 99.4±22.960, p: &amp;lt;0.001). There were significantly impaired LAS parameters in the stroke group (LA reservoir, contraction &amp; conduit strain, 22.7%, -6.6% &amp; -16.1% versus 40%, -12%, and − 27% in the control group with P &amp;lt; 0.000). ROC curve showed the best cutoff point for LA volume index is &amp;gt;42.2 ml/m2 for prediction of stroke with area under the curve (AUC): 0.7, p value is 0.005. ROC curve showed the best cutoff point for PA-TDI is &amp;gt;155.5 ms. with AUC: 0.9, 90% sensitivity, 91% specificity, p value: &amp;lt;0.001. ROC curve showed that LA reservoir strain and LA stiffness can independently predict stroke at cut-off values of 30% &amp; 24.5% respectively, P &amp;lt; 0.001. Multivariate logistic regression analysis showed that hypertension, LA volume index, LA stiffness and PA-TDI duration are independent predictors of stroke (p: &amp;lt; 0.05, &amp;lt; 0.05, &amp;lt; 0.01 and &amp;lt; 0.001 respectively). Conclusions The assessment of electromechanical asynchrony by measuring the PA-TDI duration may help to predict patients at risk for stroke. It is easy to measure without the need for special software like speckle tracking indices. We also advise patients who exceed the cutoff points of LA volume index and PA-TDI duration to receive antithrombotic therapy for better stroke prevention. Also we recommend adding PA-TDI to CHA2DS2-VASC-HSF score to assess stroke risk in patients with sinus rhythm and paroxysmal AF during their sinus rhythm intervals.

Predictors of Right vEntricular Failure aftER LVAD implantation: PREFER LVAD study

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

The added value of advanced echocardiography in dilated cardiomyopathy: looking at the right heart

Abstract Introduction and aims Right ventricular (RV) dilation and dysfunction significantly impact the prognosis of dilated cardiomyopathy (DCM) patients, and early detection of subclinical changes is mandatory. Furthermore, right atrial (RA) size and function are still often neglected in DCM patients. Accordingly, our aims were to evaluate (i) right heart chambers and tricuspid annulus (TA) subclinical remodeling, and (ii) the prognostic value of RA compared to left atrial (LA) size and function in patients with DCM without clinical RV involvement, RV pressure/volume overload or sustained atrial tachyarrhythmias by advanced echocardiography techniques. Materials and methods Sixty-eight patients out of a cohort of 106 patients with DCM (mean age 60 years, 35 men) were evaluated by comprehensive transthoracic two- (2DE) and three-dimensional (3DE) and speckle-tracking (2DSTE) echocardiography, were compared to 62 age- and sex-matched healthy controls (mean age 61 years, 32 men), and were followed-up for 37 ± 16.6 months. Results DCM patients have RV and RA global longitudinal dysfunction by 2DSTE, and higher RA minimum volumes (Vmin) and TA areas despite having normal RV volumes and ejection fraction (EF) and RA maximum volumes (Vmax) by 3DE compared to controls (Table). RA and RV strain correlate with each other (r=0.360, p=0.013 for RA reservoir and r=0.347, p=0.017 for conduit strain). TA area correlates with RA contractile strain (r=-.293, p=0.046) and RV free-wall strain (r=0.373, p=0.008), RA Vmax (r=0.513, p&amp;lt;0.001), RV (r=0.404, p=0.004 for end-diastolic and r=0.444, p=0.001 for end-systolic) and left ventricular (LV) volumes (r=0.394, p=0.016) and LV EF (r=-.361, p=0.028). RA reservoir strain (AUC=0.769) has higher value for outcome prediction compared to LA strain (p=0.02 between them). Conclusion Patients with DCM have RV longitudinal dysfunction and decreased RA function, in the absence of clinical RV involvement or atrial arrhythmias, and decreased RA strain is associated with an increased risk of hospitalization and cardiac death.Comparison of right heart parametersPrognostic value of atrial function