Left Function Research Articles

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 < 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.

Left atrial function and long-term survival after cardiac resynchronization therapy

Abstract Background Left atrial (LA) reservoir strain after CRT has been linked to long-term outcome, but the role of LA function in response to cardiac resynchronization therapy (CRT) is incompletely understood. LA dyssynchrony during left bundle branch block has negative effects on LA function beyond LA reservoir strain. We hypothesized that correction of LA dyssynchrony after CRT has added value to LA reservoir strain as a marker of long-term outcome. Purpose To explore the role of LA function in long-term survival after CRT. Methods In a recent prospective multicenter study of 168 patients, LA segmental and global strains were measured by speckle-tracking echocardiography before and 7 ± 1 months after CRT. LA reservoir strain was measured as the difference between peak and minimum global strain during the atrial cycle and LA dyssynchrony as the time delay between onset systolic stretch of the interatrial septum and LA lateral wall. Since LA reservoir strain < 18% is associated with elevated LV filling pressure, we used 18% as cutoff and for LA dyssynchrony 43 ms (mean after CRT in the present study). All-cause mortality was used as clinical endpoint during follow-up. Results After 6 years ± 21 months (mean ± SD) follow-up, 35 (21%) patients died. LA reservoir strain was significantly lower (15 ± 9% vs 20 ± 10%, p = 0.003) and LA dyssynchrony numerically higher (61 ± 68 ms vs 39 ± 69 ms, p = 0.099) in patients who died compared to survivors. LA reservoir strain ≥ 18% after CRT was associated with favorable long-term survival (HR: 0.51, 95% CI: 0.26 - 0.98) (upper panel in the Figure). LA dyssynchrony was not independently associated with mortality. However, when used in concert with LA reservoir strain ≥ 18% after CRT, it identified patients with perticularly excellent long-term survival (HR: 0.17, 95% CI: 0.05 - 0.58 vs patients with reservoir strain ≥ 18% and persistent LA dyssynchrony) (lower panel in the Figure). Patients with preserved LA reservoir strain but persistent LA dyssynchrony had similar outcome as patients with reduced LA reservoir strain (HR: 0.98, 95% CI: 0.45 - 2.12). Conclusion LA reservoir strain ≥ 18% and absence of LA dyssynchrony is associated with excellent long-term survival after CRT.LA strain after CRT and survival

Left atrial strain parameters are able to predict presence of atrial fibrillation

Abstract Background Three-dimensional speckle-tracking echocardiography allows evaluation of left atrial function, left atrial function has been assessed in various diseases for prognostication [1]. Atrial fibrillation (AF) is most common arrhythmia, and one of its manifestations is increased left atrial filling pressure and left atrial dilatation. Methods Echocardiography loops were collected between December 2019 and December 2021, only valid atrial loops, and sinus rhythm during examination. Spearman test was used for correlation matrices of left atrial parameters; uni- , multivariate and binary logistic regression to predict presence or absence of atrial fibrillation. Results A total of 116 patients (50% females) aged 76.9±11.2 were included in the analysis. Males and females differed in anthropometric and other clinical parameters. Intra- and interobserver variability was close to 1% since most of the measurements are semi-automatized. 2D and 3D left atrial volumes correlated significantly (r=0.8, P<0.0001, Fig.1). Almost all left atrial strain measurement uni- and multivariately predicted the presence of atrial fibrillation, binary logistic regression identified two most significant parameters (left atrial longitudinal strain reservoir and conduit phase, LASr, LAScd, P=0.042, P=0.044, respectively, Fig.2). LASr is significantly greater in patients without history of AF vs patient with AF history, (16±16, 10.5±7.1, respectively, P=0.012). The probability of sinus rhythm increases linearly with the increasing value of LASr. Conclusion Left atrial longitudinal strain was able to differentiate patients with paroxysmal atrial fibrillation as compared to patients without history of this arrhythmia.

Identification of genetic variants associated with exercise-induced atrial fibrillation in high-performing racehorses

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in athletes. Despite a lower burden of classical cardiovascular risk factors, the prevalence of AF in athletes is comparable to that in the general population of similar age (~13%, mean age 65.5), suggesting that exercise-induced AF may have different underlying mechanisms. The prevalence of AF in thoroughbred (TB) and standardbred (STB) racehorses is also relatively high (~5%), suggesting exercise as an independent risk factor. Due to selective breeding and complete control of pedigrees, racehorses are well-suited for genetic studies. Common and rare genetic variation explain a substantial part of AF variance, but no study has identified genetic variants associated with exercise-induced AF in any species. Objective In this project, we aimed to use the racehorse as a model to identify genetic variants associated with exercise-induced AF, and in a future study, possibly replicate the results in human athletes. Here we present preliminary results from the genome-wide association study (GWAS) of AF in racehorses. Methods We collected blood or hair samples from 181 STB and TB racehorses in which 71 had paroxysmal or persistent AF verified by ECG. We extracted DNA and performed whole-genome genotyping using a commercial equine genotyping platform (670k markers). We phased and imputed un-genotyped markers and increased the sample size of the control group, using publicly available equine data from similar breeds from the European Nucleotide Archive. We conducted a GWAS of 7.85 million markers in 71 cases and 296 controls using PLINK2 with covariates adjusted for population stratification, batch and sex. Results We identified one significant locus downstream of the protocadherin gene PCDH18 associated with AF in racehorses. The same locus has been associated with the ECG-trait P-wave terminal force in humans. Changes in P-wave terminal force is associated with increased atrial size, delayed interatrial conduction, left ventricular fibrosis and left atrial function, and considered a good predictor of AF occurrence. Several non-significant but interesting signals were also identified including the genes SLC6A15 (amino acid transport), MYBPH (myosin binding), MYF6 and MYOG (myoblast differentiation). Conclusion In these preliminary results, we have identified a new genetic locus associated with AF in racehorses. In addition, we have identified several candidate genes for further studies to elucidate the genetic background of exercise-induced AF. We aim to replicate our findings in a population of human athletes. Our results may aid the development of risk prediction tools for exercise-induced AF and new drugs for tailored treatment of AF in general.

Impact of left atrial appendage closure on left atrial function: insights from the OCEAN-LAAC registry

Abstract Background Percutaneous left atrium appendage closure (LAAC) is an effective therapy to prevent thromboembolic events among patients with atrial fibrillation (AF) (Ref 1). However, since the left atrium appendage (LAA) potentially serves as a part of the left atrium (LA) volume and a buffer for increasing LA pressure, this procedure may impair LA compliance (Ref 2). Purpose In this study, we sought to investigate the effect of LAAC on LA function. Methods/Results The OCEAN-LAAC registry is an ongoing, multicentre Japanese registry including patients who underwent LAAC in Japan (Ref 3). Among 225 patients from the registry, LA volume index (LAVI) and tricuspid regurgitation pressure gradient (TRPG) at baseline and 6 months after the procedure were analysed. In the overall population, no significant increase in LAVI (Abstract Picture 1A) and TRPG (Abstract Picture 1B) was observed (LAVI baseline vs 6 months, 55.0 [44.0, 70.0] ml/m2 vs 55.0 [42.0, 75.6] ml/m2; P = 0.31; TRPG, 25.0 [20.3, 32.0] mmHg vs 25.0 [20.0, 32.0] mmHg; P = 0.85). However, particular patients underwent an increase in LAVI (Abstract Picture 1C), and multivariable analysis showed smaller LAVI and elevated TRPG at baseline, rather than any procedural factors, were significantly associated with an increase in LAVI (Odds ratio (OR) for baseline LAVI: 0.98 [95% confidential interval (CI): 0.97 - 0.996]; OR for baseline TRPG: 1.04 [95% CI: 1.00 - 1.08]). A 5 ml/m2 increase in LAVI at a 6-month follow-up was significantly associated with subsequent heart failure hospitalization (HFH) (Hazard ratio: 3.37 [95% CI: 1.18 - 9.65]) (Abstract Picture 2A). However, this predictive value was not observed in patients with lower LAVI (≤ 55 ml/m2) at baseline; instead, it was observed in those with a baseline LAVI over 55 ml/m² (Abstract Picture 2B). Conclusions In summary, our study did not elucidate the negative impact of LAAC on LA function, yet demonstrated an increase in LAVI at 6 month follow-up was frequently observed in patients with lower LAVI and higher TRPG at baseline. Additionally, increase in LAVI was significantly associated with subsequent HFH, which was more evident in patients with higher LAVI at baseline.

Association of left atrial strain and exercise capacity among patients with hypertension: a single center study

Abstract Introduction Hypertension has been identified as one of the leading risk factors for developing cardiovascular disease in the Philippines. 1 The long term increase in afterload causes the progressive decline in both the systolic and diastolic function of hypertensive patients. There has been an increasing recognition in the role of left atrial function in the pathophysiology of several cardiac diseases, including hypertension. Purpose For patients with hypertension, exercise capacity is reduced by 30%.2 As exercise capacity is a known prognostic marker for adverse cardiovascular outcomes, identifying patients with hypertension with impaired left atrial reservoir strain may also improve cardiovascular risk stratification. With the use of two-dimensional (2D) speckle tracking echocardiography, left atrial strain can now be utilized in the evaluation of left atrial reservoir, conduit, and contractile function. Left atrial strain (LA strain) can now serve as a biomarker of adverse cardiovascular outcomes, including the exercise capacity of patients. Another goal of the study is to identify other clinical and echocardiographic factors that may affect exercise capacity Methods A single center, retrospective cross sectional study was conducted in a tertiary hospital to validate the association of left atrial strain with exercise capacity in terms of metabolic equivalent (METs) achieved during treadmill exercise echocardiography of patients diagnosed with hypertension. The primary objective of this study is to determine the left atrial strain cutoff that reliably discriminates poor, fair, average, good, or high exercise capacity. Data was obtained by conducting a chart and echocardiography review of adult patients from January 2023 to April 2023. The independent association of LA strain with METs was studied with regression analysis. Results were considered significant at p≤0.05 at 95% confidence interval. Receiver-operating characteristic curve analysis was utilized to determine the strength of the LA strain to discriminate between the different exercise capacities. Results A total of 136 patients were included in the study. LA strain, particularly the reservoir, can discriminate exercise capacity, specifically to discriminate good to high capacity from fair to average as their AUC is 0.678 (95% CI 0.58 to 0.77, p=.0001). The best cut-off is 30.2 which resulted to 80% sensitivity (95% CI 66.3 to 90) while specificity is only 51.16% (95% CI 40.1 to 62.1). Spearman rank correlation analysis showed that LA reservoir is significantly correlated with E/A and E/e’. The relationships are linear and positive. Among the other 2D echo parameters, only EDV, E/a and E/e’ were found to have a linear relationship or correlation with METS. Conclusion The study revealed that there is moderate correlation of LA reservoir strain in terms of METS achieved during treadmill stress echocardiography (rs=0.3196, p=0.0001).LA reservoir strain AUCLA strain and other echo parameters

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

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

Left atrial strain differences between hypertensive and sarcomeric left ventricular hypertrophy: a sign of sarcomeric auricular myopathy?

Abstract Introduction In clinical practice, left ventricular (LV) hypertrophy is a common finding that can be caused by physiologic or pathologic conditions. An etiologic diagnosis is extremely important because it may change the prognosis and management of the patient and his family. Left atrial (LA) dysfunction is common due to diastolic dysfunction but, in patients with sarcomeric LV hypertrophy, primary cardiomyopathy disease could also be present. Purpose To evaluate if there are differences in LA function between arterial hypertension (HT) and hypertrophic cardiomyopathy (HCM) patients. Methods 73 patients with HCM (according to ESC guidelines criteria) and 82 patients with HT (under treatment with ≥1 hypertensive drug for ≥3 months) and ≥13mm of LV hypertrophy underwent an echocardiography to assess LA function with strain analysis and LV diastolic function. Continuous normally distributed variables were compared with T-student test and categoric variables with square-chi or exact Fisher test if required, accepting as significant a p-value <0.05. Results Globally, HCM patients showed thicker LV walls and larger LA indexed volumes (18.7±4.7 vs. 13.3±0,8 mm and 44.9±20.7 vs. 30.7±8.8 ml/m2, p<0.000 for both). Also, HCM patients presented diastolic dysfunction and atrial fibrillation history in a higher frequency (31 vs. 7.6% and 16.4% vs. 0%, p<0.000 for both). LA strain was significantly lower in HCM patients as compared to the HT group (LA contractile 11.5±5.8 vs. 17.2±4.4, p<0.000; LA conduit 12.2±5.4 vs. 13.3±3.8, p=0.041; and LA reservoir 23.9±8.7 vs. 31.1±5.9, p<0.000). In the subgroup of patients with moderate-severe LV hypertrophy (<17mm) and no significant mitral regurgitation (n=103; HCM=21, HT=82), LA contractile strain remained lower in HCM as compared to HT patients (13.2±4.8% vs. 17.2±4.4%, p<0.000) (figure 1); without differences in diastolic dysfunction, LA volumes, significant mitral regurgitation or atrial fibrillation history. Conclusions Our results show that LA strain is more impaired in HCM patients as compared to HT patients. Specifically, contractile LA strain remained lower even in those patients with moderate-severe LV hypertrophy, despite having similar LV diastolic function, LA indexed volumes, significant mitral regurgitation, or atrial fibrillation history. These findings could be caused by HCM involvement of the LA myocytes. In the context of moderate-severe hypertrophy of unknown origin with non-significant mitral regurgitation, the detection of abnormally reduced LA strain could indicate the presence of an HCM.Figure 1

Left atrial parameters predict incident atrial fibrillation and flutter in patients with heart failure with reduced ejection fraction

Abstract Background Left atrial (LA) function parameters have shown prognostic value in relation to incidence of atrial fibrillation in the general population, but this remains to be investigated in patients with heart failure with reduced ejection fraction (HFrEF). Purpose This study aimed to investigate the relationship between LA function parameters and the risk of incident atrial fibrillation/atrial flutter (AF/AFL) in patients with HFrEF. Methods Subjects free of AF/AFL were retrospectively included from a HF clinic and followed using the Danish National Patient Registry. Cox proportional hazards regression was used to assess the prognostic value of LA function parameters. These included LA ejection fraction (LAEF), peak atrial longitudinal strain (PALS), peak atrial contractile strain (PACS) and LA conduit strain (LACS). In addition, multivariable Cox regression was performed to adjust for demographic and echocardiographic parameters, including LA volume index (LAVi). The LA function parameters that remained significant in adjusted analysis were examined using cubic splines, and cutoff values corresponding to a hazard ratio (HR) equal to 1 were derived from these. Results The total study population consisted of 435 subjects with a left ventricular ejection fraction (LVEF) ≤45% (mean age 65.6±11.7 years, male sex 70.1%) free from AF/AFL at baseline. During a median follow-up of 11.4 years [IQR: 10.8, 14.2], 111 (25.5%) developed AF/AFL. Subjects who met the outcome were generally older (69.0±8.8 years vs. 64.4±12.4, p<0.001), had lower baseline heart rate, and a higher prevalence of moderate or severe valve disease (12.6% vs. 3.1%, p<0.001). They also had higher LV mass index and LV internal diastolic diameter index, but similar LVEF. These subjects had larger LAVi (30 ml/m2 [IQR: 24, 38] vs. 26 ml/m2 [IQR: 20, 32], p<0.001), while LAEF (33±14.8% vs. 39±14.9%, p<0.001), PALS (20.3% [IQR: 16.2, 26.5] vs. 23.2% [IQR: 18.6, 29.6], p=0.001), and PACS (9.7% [IQR: 6.9, 13.5] vs. 12.0% [IQR: 7.8, 16.4], p=0.004) were all significantly lower. LACS was similar between groups. In univariable Cox regression, all LA parameters were significant predictors of the AF/AFL (LAEF: HR 0.98 per 1% increase, 95% CI 0.96-0.99, p=0.0002, PALS: HR 0.96 per 1% increase, 95% CI 0.94–0.98, p=0.0008, PACS: HR 0.95 per 1%, 95% CI 0.93–0.98, p=0.0024, LACS: HR 0.96, 95% per 1% increase CI 0.92–0.998, p=0.039. In adjusted analysis, however, only LAEF (HR 0.98, 95% CI 0.976-0.995, p=0.0087) and PACS (HR 0.96, 95% CI 0.993–0.999, p=0.044) remained significant. Splines were constructed for LAEF and PACS (Figure 1), and a cutoff for increased risk of AF/AFL at 38% for LAEF and 12% for PACS, respectively, were derived (Figure 2). Conclusion LAEF and PACS are associated with risk of incident AF/AFL in patients with HFrEF, independent of clinical and echocardiographic risk factors. Our results suggest an increased risk of AF/AFL at LAEF below 38% and PACS below 12%.Figure 1 SplinesFigure 2 Cumulative incident curves

The predictive value of left atrial functional parameters for recurrence of atrial fibrillation after catheter ablation in patients

Abstract Background Catheter ablation (CA) is a first-line treatment option for patients with symptomatic or drug-refractory atrial fibrillation (AF), yet the recurrence rate of AF post-CA remains considerably high. Studies have reported that left atrial (LA) functional parameters can serve as predictive factors for AF recurrence, however, the results remains controversial. Purpose This study aims to investigate the predictive value of LA functional parameters for AF recurrence following CA in patients. Methods We prospectively enrolled patients with AF who underwent CA for the first time from June 2022 to May 2023 and met the inclusion criteria at our institution. All patients underwent pre-ablation evaluation of LA structure and function, including LA diameter (LAD), LA maximum volume (LAVmax), LA minimum volume (LAVmin), LA pre-systolic volume (LAVpre), LA reservoir strain (LASr), LA strain conduit (LAScd), LA contraction strain (LASct), and LA ejection fraction (LAEF) using three-dimensional speckle tracking echocardiography. AF recurrence was defined as atrial tachycardia occurring 3 months after ablation and lasting longer than 30s. Patients were followed up for 9 months post-CA , and the primary end point was any atrial tachycardia occurring at 3 months after ablation. Results A total of 85 patients with AF were ultimately included in this study, with an average age of 68.9±11.0 years, 54.2% of whom were male. During the 9-month follow-up, 30 patients (35.29%) experienced recurrence postoperatively, while 55 patients (64.71%) still maintained sinus rhythm. Compared with the AF non-recurrence group, the AF recurrence group had significantly increased LAD (46.4±5.5mm vs. 42.3±4.5mm, p<0.05), LAVmax (80.7±21.3mL vs. 67.1±22.0mL, p<0.05), LAVmin (63.8±18.0mL vs. 42.8±16.9mL, p<0.05) and LAVpre (72.4±19.4mL vs. 53.9±16.8mL, p<0.05). Meanwhile, in AF recurrence group, LAEF (21.7±6.8% vs. 37.5±8.0%, p<0.05), LASr (5.1±3.1% vs. 12.0±5.4%, p<0.05), LAScd (-4.0±3.6% vs. -7.3±5.7%, p<0.05), and LASct (-1.0±3.8% vs. -3.3±4.9%, p<0.05) were significantly decreased. Multivariate logistic regression analysis revealed that LASr (OR=0.640, 95%CI 0.425-0.964, p<0.05) and LAEF (OR=0.816, 95%CI 0.694-0.960, p<0.05) were independent risk factors for predicting AF recurrence. ROC curve analysis showed that both LAEF (AUC=0.935, 95%CI 0.871-0.999) and LASr (AUC=0.903, 95%CI 0.833-0.973) possess high predictive values. Furthermore, the combined model of LAEF and LASr (AUC=0.954, 95%CI 0.905-1.000) had a greater predictive value than any one of the two indicators (p<0.05). Conclusion Taken together, these findings indicate that LAEF and LASr are independent predictors of AF recurrence following CA in patients with AF. Combination of the two indicators can more accurately assess the risk of recurrence in AF patients post-CA.

The impact of preoperative four-chamber strain on failure of the maze IV procedure for atrial fibrillation: insights from conventional and speckle-tracking echocardiography

Abstract Background Prior studies have linked decreased left atrial (LA) and left ventricular (LV) function to the failure of both catheter ablation and surgery for atrial fibrillation (AF). Yet, the effects of right atrial (RA) and right ventricular (RV) function on the failure of interventional therapy remain unexplored. This study evaluates four-chamber strain parameters using conventional echocardiography and speckle-tracking analysis to evaluate the contributions of preoperative left heart and right heart function to the failure of surgery for atrial fibrillation. Methods We retrospectively analyzed 821 patients who had surgical AF ablation, using pre- and postoperative data from electronic records to assess AF recurrence and thromboembolic events. Of these, 531 had LA ablation only and 290 had bi-atrial Maze-IV procedures. Four-chamber strain was evaluated via speckle-tracking on preoperative echos with TomTec Arena, excluding low-quality images. Univariate and multivariate logistic regression analyses were conducted to assess the influence of AF duration, LV ejection fraction, age, and gender on post-PAF surgery AF recurrence, thromboembolic events with results shown as odds ratios (ORs) in the table. An OR over 1.00 indicates a higher recurrence risk per variable increment. SAS software was used for all statistical analysis. Results In our cohort with a median age of 67.4±11.0 (46.2% female), unadjusted analyses revealed that increased LA and RA volumes and decreased RV free wall strain were significantly associated with AF recurrence post-surgical ablation. Conversely, each unit decrease in LA and RA peak reservoir strain corresponded to a 6% increase in the risk of AF recurrence, indicating an inverse relationship. Adjusted analyses for LA and RA end diastolic volumes and strain values showed a similar direction of association with AF recurrence, though these were not statistically significant. Similarly, lower LA and RA peak strains and larger atrial volumes were suggestive of an increased risk for postoperative thromboembolic stroke, but did not reach statistical significance, potentially due to the low event rate (1.8% of the cohort). Conclusion Conventional echocardiography offers a practical tool for identifying patients at high risk for AF recurrence and potential thromboembolic events after AF ablation surgery. Our study confirms that reduced preoperative LA, RA and RV strain values and enlarged volumes of LA and RA are strongly associated with AF recurrence following surgical ablation. Additionally, RA strain and volume are as predictive as LA metrics, underscoring their importance in risk stratification. These echocardiographic parameters may also hold value in forecasting the likelihood of postoperative stroke.

Analysis of the left atrial appendage function by intracardiac echocardiography in patients with atrial fibrillation

Abstract Introduction Intracardiac echocardiography (ICE) is frequently performed during catheter ablation procedures in order to guide the transseptal puncture and has been recently used to evaluate the morphology of the LAA. Purpose The objective of this study was to evaluate the feasibility of using an ICE catheter placed in the coronary sinus (CS) to delineate the LAA function during catheter ablation for atrial fibrillation. Methods We included 21 consecutive patients (age 62±9 years, 5 women, 6 paroxysmal AF) who underwent catheter ablation for AF. An 8-Fr phased-array ICE catheter was used to obtain images of the LAA, while in sinus rhythm. The LAA was visualized with the ICE probe placed sequentially in the left atrium (LA, Figure A), with the ultrasound section plane parallel to the long axis of the left ventricle (LV), and in the CS, with the ultrasound section plane perpendicular to the LV long axis (Figure B). LAA emptying flow velocity, and LAA fractional area change (FAC) were used to evaluate LAA function. There were no procedural complications. Results ICE imaging was possible in all cases. The LAA peak flow velocity was similar when the ICE catheter was placed in the LA and in the CS (64±7 cm/s and 62±5cm/s respectively, P=NS). The LAA FAC was significantly lower when the ICE catheter was placed in the CS when compared to an LA location (14±6% vs 36±14%; P<0.001). The LAA FAC measured from the LA correlated with the mitral annular plane systolic excursion while the LAA FAC measured from the CS did not. Thus, LAA contraction in a plane perpendicular to the LV long axis is independent of the LV longitudinal contraction. These results suggest that in our patient group most of the LAA contraction was due to the longitudinal movement of the LV base during systole and diastole. Conclusions Imaging of LAA using an ICE probe positioned in the LA and CS was feasible in all cases. The LV longitudinal contraction appears to impact the LAA function.

Left atrial cardiomyopathy predicts stroke recurrence and atrial fibrillation

Abstract Background Markers of atrial cardiomyopathy, encompassing both left atrial (LA) structure and function, have been linked to an increased long-term risk of ischemic stroke and atrial fibrillation (AF). However, the short-term risk associated with these markers in patients with stroke without previously known or detected AF during stroke workup remains insufficiently characterized. Purpose To investigate the association between functional and structural markers of atrial cardiomypathy using cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) in patients with stroke of either i) undetermined etiology or ii) small or large-vessel stroke and the recurrence of stroke or new-onset AF. Methods Between 2019 and 2021 we consecutively included 91 patients with a recent stroke (<30 days) without known or detected AF during at least 48-hours of continuous monitoring. All patients had CMR with LGE to determine LA emptying fraction, LA volumes, and LA fibrosis. The primary endpoint was a composite of stroke recurrence or new-onset AF. Results Baseline characteristics are presented in Table 1. Over a median follow-up of 2.3 years, fourteen patients (15%) reached the combined endpoint of stroke or new-onset AF. Multivariable cause specific regression analysis demonstrated that a lower LA emptying fraction was associated with the primary endpoint (hazard ratio [HR], 1.41 per 5% decrease [95% CI, 1.09–1.82]). LA volumes and LA fibrosis did not show any associations with the combined endpoint (Table 2). Subgroup analysis indicated that the results were predominantly driven by new-onset AF in patients with stroke of undetermined etiology Conclusion Our results suggests that LA emptying fraction, measured using CMR, may serve as a prognostic indicator for stroke recurrence or new-onset atrial fibrillation in patients without detected AF, especially in those with stroke of undetermined etiology. Surprisingly, LA fibrosis was not associated with either recurrence of stroke or new-onset AF.

Measures of left atrial structure and function predict cardiovascular death in patients with heart failure with reduced ejection fraction

Abstract Background The role of the left atrium (LA) is increasingly recognized as a predictor of cardiovascular health outcomes. This study aimed to investigate the prognostic value of LA strain in relation to cardiovascular (CV) death in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods In this retrospective cohort analysis, patients diagnosed with stable HFrEF and free from atrial fibrillation at baseline were included. All patients had a Left Ventricular Ejection Fraction (LVEF) of 45% or below at the time of referral. Baseline clinical and echocardiographic parameters were collected from the database of the HF outpatient clinic, and data on CV death was gathered through the Danish National Patient Registry. LA function was assessed by means of LA emptying fraction (LAEF), peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA conduit strain (LACS). Uni- and multivariable Cox regression models adjusted for clinical and echocardiographic baseline characteristics were used to determine the association between LA parameters and CV death. Cubic splines were used to identify cutoff values for LA parameters corresponding to a HR of 1. Results The study population consisted of 495 patients (mean age 66 ±11.5 years, 71% males). During a follow-up of 10.9 years [IQR: 6.2; 13.4], 134 (27%) patients reached the outcome of CV death. At baseline, patients who died of CV death were generally older (70.7±9.7 years vs. 64.2±11.7, p<0.001), had a higher prevalence of diabetes (25.4% vs. 13.9%, p=0.004), and a higher prevalence of moderate or severe valve disease (11.2% vs. 3.9%, p=0.004), as well as a lower LVEF (25.1%±8.5 vs. 29.4±8.9, p<0.001). Among LA parameters, the patients who met the outcome had a significantly lower LAEF (30.5% [IQR: 18.0; 42.0] vs. 38.9% [IQR: 29.0; 49.3], p<0.001), PALS (18.2% [IQR: 12.7; 24.4] vs. 23.0% [IQR: 18.3; 29.9], p<0.001), PACS (7.7% [IQR: 2.9; 13.6] vs. 11.7% [IQR: 7.9; 16.4], p<0.001), and LACS (9.4% [IQR: 7.2 ; 12.4] vs. 11.9% [IQR: 8.8; 15.0], p<0.001). Lower levels of all LA parameters were associated with an increased risk of CV death in univariable analysis (p<0.0001 for all parameters). However, in multivariable analysis, only LAEF (HR 0.99 per 1% increase, 95% CI 0.973-0.999, p=0.039), PALS (HR 0.96 per 1% increase, 95% CI 0.931–0.991, p=0.011), and PACS (HR 0.94 per 1% increase, 95% CI 0.90–0.98, p=0.002) remained significant. Splines for LAEF, PALS, and PACS were constructed with identified cutoff points for higher CV death risk (Figure 1), which were utilized to generate Kaplan-Meier curves (Figure 2). Conclusion Lower LA parameters, including LAEF, PALS, and PACS, are associated with increased risk of CV death in patients with HFrEF.Spline curves for LAEF, PALS, and PACS.Kaplan-Meier survival estimates for CVD

Differences in left atrial stain, endothelial glycocalyx, arterial elasticity and myocardial efficiency between ESUS, lacunar, cardioembolic and atherosclerotic type of stroke

Abstract Background Patients with stroke are at greater risk of developing cardiovascular complications. Purpose We addressed endothelial glycocalyx, arterial stiffness, left atrial and ventricular function in patients with lacunar, atherosclerotic, cardioembolic and stroke of undetermined source (ESUS). Methods We recruited 194 patients (aged 58.8± 10.8 years old) with acute cerebral stroke (47 lacunar, 50 atherosclerotic,48 ESUS and 49 cardioembolic) and 50 controls with similar risk factors and 40 controls with similar profile regarding common risk factors (diabetes, hypertension, hyperlipidemia, coronary artery disease, smoking; p>0.05 for all comparisons). We measured: (1) perfused boundary region (PBR) of the sublingual microvessels (diameter range 5–25 μm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity carotid-to-femoral (PWV), central systolic blood pressure (cSBP), and central diastolic blood pressure (cDBP), (3) Left atrial (LA) strain using speckle-tracking imaging, (4) left ventricular global longitudinal strain and (5) left ventricular myocardial work index (GWI), constructive work (GCW), wasted work (GWW) and work efficiency (GWE), (6) ventriculoarterial coupling, expressed by the ratio PWV/GLS. Results Compared with controls, patients with stroke had higher PWV (11.98±3.21 vs 9.61±1.28 m/sec, p=0.001), PBR (2.20±0.31 vs 1.94±0.20, p=0.019) and central SBP (137.41±24.83 vs 121.15±17.46 mmHg, p=0.018), while LV ventricular (-16.44±4.70 vs -20.89±2.45%, p=0.001) and atrial deformation (26.81±9.32 vs 37.05±5.08%, p<0.001) were more impaired in patients with stroke (p < 0.05). Patients with ESUS had more impaired LA reservoir strain and contraction strain compared to the other 2 stroke types (ESUS 22.9±8.72%, -13.90±4.96%, Lacunar 29.71±10.52%, -16.11±6.10%, atherosclerotic 26.78±10.14%, -13.74±5.65%, p<0.05). Also, patients with ESUS demonstrated better PBR compared to the lacunar and atherosclerotic types (ESUS 2.10±0.27 μm, Lacunar 2.26±0.29 μm, atherosclerotic 2.19±0.29μm, p<0.05). Patients with atherosclerotic stroke had higher PWV compared with other stroke types (Atherosclerotic: 13.59±3.87 m/sec, Lacunar: 11.41±2.35 m/sec, Cardioembolic: 10.66±3.28 m/sec, ESUS: 11.72±2.67 m/sec). Also, patients with atherosclerotic stroke demonstrated the worst PWV/GLS ratio (Atherosclerotic: -0.97±0.35, Lacunar: -0.69±0.25, Cardioembolic: -0.76±0.21, ESUS: -0.70±0.28). Patients with cardioembolic stroke showed similar trend with ESUS, as far LA strain is considered. Conclusion Patients with stroke have impaired atrial strain, endothelial glycocalyx and arterial stiffness, compared with controls. Arterial stiffness and ventriculoarterial coupling are more affected in atherosclerotic strokes. LA strain is more impaired in the ESUS and cardioembolic stroke albeit that endocalyx, though abnormal,is less impaired in these stroke types.

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.

Long-term changes in cardiac geometry and mechanics after bariatric surgery- insights from the FatWest study

Abstract Background Patients with severe obesity have a high prevalence of subclinical cardiac organ damage including impaired longitudinal and radial cardiac mechanics. Previous studies on the impact of bariatric surgery on cardiac remodeling, most of them with short patient follow-up, have yielded inconsistent results. Purpose To assess progressive changes in cardiac geometry and mechanics up to five years following bariatric surgery. Methods In the prospective Bariatric Surgery on the West Coast of Norway (FatWest) study, cardiac remodeling was assessed by 2D echocardiography preoperatively and at six months, one year and five years after Roux-en-Y gastric bypass in a cohort of 97 patients (44±10 years, 72% women, body mass index [BMI] 41.8±4.8 kg/m²). Excess weight loss (EWL) was calculated as: absolute weight loss/(initial weight-ideal weight)x100. Left ventricular (LV) size was assessed by the LV mass/ height^2.7, LV longitudinal mechanics by the peak global longitudinal strain (GLS) and radial mechanics by the midwall shortening (MWS). LV myocardial oxygen demand was estimated from the LV mass-wall stress-heart rate product. Right ventricular diameter was measured in the basal one-third of the ventricular cavity. Left atrial (LA) reservoir function was assessed by the LA emptying fraction. Results After a mean follow-up of 63±13 months, the average postoperative EWL was 66%. Overall, both right ventricular diameter, LV mass index, LV GLS, myocardial oxygen demand and LAEF (68% vs. 64%) improved significantly at the 5-year follow-up (all p<0.05), while MWS remained unchanged (Figure). Prevalence of normal LV geometry increased gradually from 56% to 80%, while that of LV hypertrophy fell from 36% to 16% (p<0.001). Analyses of temporal trends showed that improvement in BMI, LV mass and LV GLS occurred during the first postoperative year (Figure). In Cox regression analysis, a low 5-year GLS was associated with preoperative hypertension after adjustment for age, sex, preoperative diabetes mellitus, and postoperative changes in BMI, mean blood pressure and myocardial oxygen demand (p<0.01). In a similar linear model, after adjustment for the same covariates, LV mass index at the 5-year follow-up was independently related to the magnitude of the postoperative BMI reduction (R² = 0.58, p<0.001). Conclusion Ventricular size and longitudinal mechanics are significantly improved 5 years after bariatric surgery, with the reverse remodeling occurring during the first postoperative year. Residual abnormal 5-year LV geometry and mechanics are related to preoperative hypertension and suboptimal BMI reduction.Figure

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 (< 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

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<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

Left atrial volumetric-mechanical coupling index as a marker of subclinical primary heart involvement in systemic sclerosis

Abstract Background Primary heart involvement in systemic sclerosis (SSc) is a common yet often clinically silent marker of poor prognosis. Up to 80% of patients have histopathological evidence of heart involvement, highlighting the need for better screening and diagnostic methods. N-terminal pro-brain natriuretic peptide (NTproBNP), a well-established cardiac biomarker, is often increased in patients with SSc, but with a not fully understood mechanism. Meanwhile, left atrial volumetric-mechanical coupling index (LACI), a new echocardiographic parameter, has been shown to predict cardiovascular outcomes in heart failure patients and the general population, but it has not been studied in SSc. Purpose To identify new echocardiographic parameters, particularly related to left atrial volume and function, as markers of increased NTproBNP in SSc patients without overt heart involvement. Methods Consecutive SSc patients without overt heart disease referred for routine cardiac screening underwent 2D and 3D transthoracic echocardiography, including atrial and ventricular strain analysis. LACI was calculated by both 2D and 3D echocardiography as the ratio between the left atrial volume index and the tissue-Doppler-imaging septal a’ velocity. Patients with significant structural and functional changes suggestive of systolic or diastolic dysfunction or pulmonary hypertension, and those with impaired global left ventricular strain were excluded. Logistic regression, Pearson correlation coefficients, and area under the receiver-operating characteristic curve (AUC) are used to analyze the association and predictive power of LACI for elevated NTproBNP. Results A total of 36 SSc patients (55±10 years old; 34 (94%) women; mean disease duration 14±11 years) were included. Sixteen (44.4%) had diffuse cutaneous involvement (dcSSc). Seventeen (47%) patients had increased NTproBNP levels (i.e. >125 pg/mL). Among all tested variables, 3D LACI had the best correlation with NTproBNP values (r = 0.63, p<0.001). A 3D LACI of >2 associated with NTproBNP of >125 pg/mL (odds ratio 7.33 [95%CI 1.38-38.8]; p=0.01) and predicted these increased values with a sensitivity of 76.9% and a specificity of 81.2% (AUC 0.78). NTproBNP was also correlated with 2D LACI (r=0.55, p<0.001), peak left atrial longitudinal strain (r=-0.42, p=0.01), and left atrial contraction strain (r=0.48, p=0.005). Compared to patients with limited cutaneous involvement, those with dcSSc had higher NTproBNP values (250±139.6 vs 107.2±110.9 pg/mL, p=0.001), higher 3D LACI values (2.6±0.9 vs 1.9±0.5, p=0.02), with similar left atrial and ventricular strain parameters. Conclusion Left atrial volumetric-mechanical coupling index assessed by 3D echocardiography is significantly associated with and predictive of elevated NTproBNP levels in SSc patients without overt heart disease and may be a potentially useful non-invasive marker for screening for early subclinical heart involvement in SSc patients.