Left Remodeling Research Articles

How different types of cardiomyopathy with hypertrophic phenotype affect left atrial remodeling and function

Abstract Background Left atrial (LA) dysfunction is a common feature in hypertrophic cardiomyopathies. How the underlying etiology and pathophysiology of different cardiomyopathies affects LA remodeling and function remains unexplored. Purpose The aim of our study is to investigate the influence of various cardiomyopathies with hypertrophic phenotype on LA remodeling and function. Methods Patients with left ventricular (LV) hypertrophic phenotype who underwent cardiac magnetic resonance (CMR) were included. A group of patients with a normal CMR was included as a control group. CMR acquisitions used for clinical indication of heart failure diagnosis and etiology were retrospectively analyzed to obtain LA reservoir, conduit, and booster strain, left atrioventricular coupling index (LACI) and LA sphericity. Differences between groups were assessed. To investigate the independent clinical associates of LA reservoir, conduit and booster strain, multivariable linear regression analyses were performed. Results A total of 375 individuals were analyzed including 321 patients diagnosed with LV hypertrophy and 54 patients with a normal CMR. Of the 321 patients with LV hypertrophy, 148 were diagnosed with hypertrophic cardiomyopathy (HCM), 35 with cardiac amyloidosis (CA), 41 with hypertensive cardiomyopathy (HTN) and 97 with severe asymptomatic aortic stenosis (AS). CMR LA characteristic and strain analysis results are summarized in Figure 1. The indexed LA end-systolic volume (iLAVmax), indexed LA end-diastolic volume (iLAVmin) and LA sphericity were larger in patients with CA when compared to other groups (all p<0.05). CA patients displayed more left atrioventricular uncoupling (lower LACI) when compared to individuals with HCM, HTN, AS, and controls (all p<0.001), while no significant differences were observed across other groups. CA patients exhibited lower LA reservoir and booster strains compared to the other groups (all p<0.05), whereas no significant differences were observed across other hypertrophic phenotype diseases. Age, iLAVMax and LACI were independently associated with all the three LA strain components (Figure 2, all p<0.05). Conclusions LA remodeling and function are affected differently across the various etiologies of LV hypertrophy. CA patients exhibit more pronounced atrial involvement, whereas those with HCM, asymptomatic AS, and HTN display similar patterns of atrial dysfunction and remodeling. Additionally, CMR-derived iLAVmax and LACI are independently correlated with LA function.

Prognostic impact of left atrial reverse remodeling in patients with ADHF-HFpEF regardless of atrial fibrillation -PURSUIT-HFpEF Registry-

Abstract Background Left atrial (LA) dilatation is associated with increased mortality in patients with cardiovascular disease including heart failure (HF) and LA reverse remodeling (LARR) was reported to be associated with favorable outcomes in patients with HF. However, it remains to be clarified whether LARR could have prognostic value in patients with HF with preserved ejection fraction (HFpEF). Purpose The purpose of this study is to elucidate whether LARR is associated with clinical outcome in patients with HFpEF in relation to the presence of atrial fibrillation (AF). Methods We prospectively studied 492 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome during the first year postdischarge. Echocardiography was performed just before discharge and at 1 year after discharge. LARR was defined as the reduction of 15% or more in left atrial end-systolic volume (LAV). The primary outcome was rehospitalization for worsening heart failure. Results All study patients were divided into 2 groups according to the presence of AF at discharge (AF group, n=182 and non-AF group, n=310). During a mean follow-up period of 1.4±1.2 years, 78 patients were rehospitalized for worsening heart failure (37 patients in AF group and 41 in non-AF group). ΔLAV, the degree of reduction in LAV during the first year postdischarge, was significantly independently associated with primary outcome after multivariable adjustment both in AF group (p=0.033, HR 0.992 [0.984-0.999]) and non-AF group (p=0.021, HR 0.986 [0.974-0.998]). Kaplan-Meier analysis revealed that patients with LARR had significantly lower risk for primary outcome than those without LARR not only in the whole study patients (8% vs 20%, p=0.001) but also both in AF group (9% vs 24% p=0.013) and in non-AF group (8% vs 16% p=0.043). Among clinical characteristics during the index hospitalization, the presence of AF and prior HF hospitalization were significantly independently associated with LARR at multivariate Cox logistic regression analysis (p=0.006, OR 0.554 [0.364-0.843] and p=0.007, OR 0.491 [0.292-0.826], respectively). Conclusion(s) The left atrial reverse remodeling could have the prognostic impact in patients with ADHF-HFpEF regardless of the presence of atrial fibrillation.Kaplan-Meier curves in AF and non-AF

Left atrial remodeling and novel biomarkers in obese patients with heart failure with preserved ejection fraction compared to type-2-diabetics and obese controls: a cardiac magnetic resonance study

Abstract Background Elevated filling pressures and subsequent left atrial (LA) dilation are common findings in heart failure with preserved ejection fraction (HFpEF), reflecting a chronic state of the disease and holding prognostic value. HFpEF is thought to develop through a long-term pro-inflammatory state triggered by comorbidities, such as obesity and type 2 diabetes mellitus (T2DM). Emerging biomarkers have shown associations with structural remodeling, but also increased myocardial stiffness. Purpose To elucidate the relationship between LA volume and function, and prognostic biomarkers (NT-proBNP, BNP-32, IL1R1, Galectin-3, and Pentraxin-3) in an obese cohort with T2DM or HFpEF and T2DM, versus healthy obese controls. Methods We conducted a prospective cohort study of 35 obese participants, divided into three groups: T2DM (n=16), HFpEF with T2DM (NYHA II-III, n=13), and healthy obese controls (n=6). Each subject underwent comprehensive CMR at a 3T scanner to assess LA strain and volume. Atrial strain was assessed on 2- and 4-chamber view cine images by experienced CMR investigators using dedicated software. Routine labs and serum levels of biomarkers were measured. If labs or images were repeated, the average was calculated. Statistical significance was determined through ANOVA and student’s t-test for group comparisons and Pearson correlation for associations between LA parameters and biomarker levels. Results Cohorts were evenly matched in terms of demographics, vital signs, and ventricular volumes and functions, as depicted in Table 1. Only one patient in the HFpEF subgroup reported history of atrial fibrillation. Both minimum and maximum LA volumes were significantly elevated in the HFpEF group compared to the T2DM and control groups (p < 0.018). LA strain (conduit, reservoir, and booster) was notably compromised in the HFpEF cohort, contrasting with the obese T2DM group where LA strain values did not differ significantly from those observed in obese controls (Figure 1). Biomarker analysis revealed a marked increase of NT-proBNP, BNP-32, Galectin-3, and Pentraxin-3 in the HFpEF cohort. In the HFpEF cohort, IL1R1 was the only biomarker that was strongly associated with higher left ventricular enddiastolic (r=0.69, p=0.003) and endsystolic volumes (r=0.75, p=0.009). Moreover, IL1R1 was the only biomarker associated with atrial functional changes (booster strain, r=-0.57, p=0.043) in the HFpEF patients. Our findings indicate that ILR1 plays a crucial role in the cardiometabolic (obesity-T2DM) HFpEF phenotype, with its activation leading to advanced cardiac remodeling. Conclusion Obese HFpEF patients with T2DM showed severely altered left atrial morphology and function compared to those that are only obese or obese with T2DM. Moreover, our findings revealed that atrial remodeling in this population is driven by pro-fibrotic inflammatory pathways.Characteristics of the study cohortLeft atrial strain analysis

Cardiac chamber three-dimensional volumes and deformation predict clinical outcomes in chronic mitral regurgitation

Abstract Background In patients with mitral regurgitation (MR), cardiac remodeling assessed by two-dimensional (2D) echocardiographic linear indexes is highly variable and not suitable for individualized risk assessment. Purpose To evaluate whether measurements of myocardial strain and left atrial (LA), left ventricular (LV) and right ventricular (RV) three-dimensional (3D) volumes improve risk assessment in MR. Methods In the prospective 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study (3D-PRIME), 176 patients with significant (moderate or greater) MR were investigated with 2D/3D echocardiography. Referral criteria for mitral intervention followed current guidelines. LA remodeling was assessed by the maximum and minimum 3D LA volume (3D-LAV), peak reservoir strain (LASr), and stiffness (i.e. the ratio: mitral peak E-wave divided by the annular e’ velocity (E/e´) / LASr). LV and RV were considered dilated in case of increased 3D end-diastolic (LV>=86/74 and RV>=87/74ml/m2 in men/women) and end-systolic volumes indexed for body surface area (LV>=41/33 and RV>=44/36ml/m2 in men/women). Peak global longitudinal strain was measured in the LV (LV-GLS) and the RV free wall (RV-FWS). The primary outcome was a composite of mitral valve surgery, percutaneous mitral edge-to-edge repair and death. Results During a 14 [8-24] months follow-up, the patients (70±13 years, 39% women) experienced 73 events including 14 deaths. In univariate survival analyses, LV and RV dilatation, but not LV-GLS and RV-FWS, were associated with the primary outcome (Figure) and had superior predictive value to 2D volumes and diameters (p<0.05). On contrary, both atrial size and function predicted outcome, with 3D-LAV (HR 1.01, 95% CI 1.00-1.01), LASr (HR 1.03, 95% CI 1.01-1.06) and increased LA stiffness (Figure) all significant predictors of events (p<0.05). In multivariate Cox analysis with adjustment for age, sex, body mass index and MR etiology, dilated LV (HR 2.6, 95% CI 1.5-4.4), dilated RV (HR 2.0, 95% CI 1.1-3.6) and increased LA stiffness ((HR 2.4, 95% CI 1.3-4.6) were independently associated with higher rate of events (p<0.05). Conclusion In patients with moderate or greater MR, increased cardiac chamber 3D volumes and LA stiffness, as well as impaired LA reservoir strain are associated with higher risk of disease progression towards mitral valve intervention and death. Our findings indicate that assessment of both cardiac chamber 3D size and LA deformation can contribute to increased diagnostic and prognostic precision in patients with MR.

The impact of diabetes on cardiac remodelling after transcatheter aortic valve implantation

Abstract Background Transcatheter aortic valve implantation (TAVI) induces reverse cardiac remodelling, an important outcome associated with lower mortality. Diabetes mellitus (DM) is common among TAVI patients and is one of the fastest growing chronic conditions worldwide. Despite its propensity to adversely affect myocardium, the influence of DM on post-TAVI remodelling remains poorly understood. Purpose To characterise the influence of DM on cardiac remodelling following TAVI. Methods Retrospective analysis of 202 patients undergoing TAVI at an Australian tertiary centre. 12-month myocardial remodelling was compared between DM and no DM groups. Results Of 202 patients, median age 82 (IQR: 76, 86) years, 50% female and median STS score 3.5 (2.5, 4.9), 62 (31%) had Type II DM. A robust multivariable analysis (C-Statistic 0.83) revealed DM (adjusted odds ratio [aOR] 2.3, p=0.042) and ≥ mild post-procedural paravalvular regurgitation (aOR 2.5, p=0.027) were independent predictors of poor left-ventricular mass index regression (LVMIr). Among diabetic patients, suboptimal disease control was associated with inferior LVMIr (6% vs -9%, p=0.011), while insulin dependency was not (-3% vs 2%, p=0.489). At 12-months, no differences were found in left-atrial remodelling, left and right-ventricular function, and prosthetic valve performance between DM and no DM groups. Poor LVMIr was associated with lower survival in Kaplan Meier analysis (65% vs 85%, log-rank p=0.049). Conclusion Among patients undergoing TAVI, those with DM demonstrate poorer LVMIr at 12-months. Improved glycaemic control may serve as an important strategy to optimise myocardial remodelling in diabetic patients undergoing TAVI.12-Month LVMI Regression

Effects of cardiac resynchronization therapy and physiologicaL pacing on left atrioventricular coupling index: the REPHYL-LACI study

Abstract Introduction Cardiac dyssynchrony and right ventricular pacing are associated with left atrial (LA) remodeling and atrioventricular uncoupling. Cardiac resynchronization therapy -CRT and conduction system pacing –CSP are important therapeutic options. Left atrioventricular coupling index (LACI) is a novel imaging parameter useful to describe the relationship between LA and left ventricle (LV). It could be measured as the ratio between LA end-diastolic volume (EDV) and the LV EDV or, alternatively, as the LA volume indexed for body surface area (LAVi) divided for a’ measured by tissue Doppler imaging (TDI) at medial mitral annulus level. Higher values indicate greater impairment of atrioventricular coupling. However, LACI has not been investigated in patients treated with CRT or CSP, and there is no comparison data about the two different measurement methodologies with echocardiography. Purpose To study the effects of CRT/CSP on LACI. Methods We retrospectively collected clinical, ECG and echocardiographic data of patients treated with standard CRT or CSP. Changes between baseline and follow-up (i.e. before and after CRT/CSP) were tested for significance. Baseline features were compared with these of a control group of patients without established major cardiovascular diseases. Results We enrolled fifty-six patients (median age at first echo 78[72.5-82]years; males 70%) and 56 controls (median age 77[72.5-83]years, p=0.974; males 57%, p= 0.170). Main clinical/instrumental data are shown in Table 1 and 2. In patients treated with CRT/CSP baseline LACIv (LAVid/LV EDV) was significantly lower than in controls (31[21-44]%vs34[29-48]%, p=0.040), despite higher LAVi and LV volumes in the first group (p<0.0001 for both). Conversely, LACId (LAVi/TDI-a’) was significantly higher in the CRT/CSP (4.48[2.81-8.28]vs2.89[2.36-3.67]mlxsecond/cm-1, p<0.0001). After a median follow-up of 515[282-1326]days, patients treated with CRT/CSP showed a significant increase of both LACIv (40[29-50]%, p=0.004) and LACId (4.95[3.77-9.89], p<0.0001). This worsening of atrioventricular coupling was accompanied by a trending LA dilatation with significant reduction of its reservoir function compared to baseline (expansion index 0.58[0.38-1.30]vs0.43[0.29-0.58], p=0.0002), despite a tendency toward stability or improvement of LV size and systolic/diastolic parameters. Conclusions In patients treated with CRT/CSP there is a worsening of LACI over time. We can speculate that the detrimental effects of artificial pacing might not be adequately counterbalanced by CRT/CSP, or that LV and LA pathology follow alternative trajectories with different responses to treatments. Moreover, the measurement of LACId should be probably avoided in patients with conduction disorders or paced. Further larger case-control studies are needed to clarify the usefulness of LACI as a valid parameter to assess atrioventricular coupling and its changes over time in patients treated with CRT/CSP.

Comparison of pulsed field ablation versus cryoballon and radiofrequency ablation for pulmonary vein isolation in atrial fibrillation patients with heart failure

Abstract Background Pulmonary vein isolation (PVI) is the gold standard for atrial fibrillation (AF) ablation and can be achieved by a variety of technical methodes. While thermal ablation modalities (TA), such as cryoballon (CB) and radiofrequency ablation (RF) have been established as the standard approaches, PFA has been introduced as a nvel non-thermal modality showing comparable safety and procedural efficiency. Despite the high incidence of AF in heart failure (HF) patients, data comparing outcomes of HF patients undergoing PVI by either PFA or thermal ablation (RFA/CB) are limited. Purpose This study’s aim was to compare the efficacy and safety of PFA for AF ablation versus CB/RFA in HF patients. Methods Consecutive HF patients with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction undergoing PVI for AF by either PFA or CB/RFA at our institution were included. The primary end-point was time to death or recurrence of AF. Secondary end-points were periprocedural complications and clinical and echocardiographic parameters. Results We included 140 HF patients who underwent PVI either by PFA (PFA group, 76 patients) or thermal ablation approaches (TA group, 64 patients). Our patients had a mean age of 69 years and were predominantly male (62%). There was no significant difference in the baseline characteristics and in the type of AF between both groups (42% with ParAF, 45% with PersAF) and 13% LSPersAF). The distribution of heart failure types was similar between both groups: HFpEF (PFA: 71%, TA: 75%), HFmrEF (PFA: 21%, TA: 20%) and HFrEF (PFA: 8 %, TA: 5%). After the 365-days follow-up period we observed no significant difference for the primary end-point between both groups (HR: 0.79, 95% CI 0.35-1.78; p=0.575). In total 58% of the PFA patients and 59% of the TA group were still free from AF. While symptom improvement was documented in both groups, patients in the PFA group showed significant improvement of left atrial volume index (p = 0.014), NT-pro BNP levels (p = 0.046), and left ventricular ejection fraction (LVEF) (p = 0.005). Conclusion In this study, PFA and thermal ablation modalities showed comparable results in terms of safety and procedural efficiency in patients with heart failure. Since previous studies have shown that HF patients with AF benefit from PVI using thermal ablation modalities, our results suggest that PFA might also be a promising ablation method in this vulnerable population, inducing left atrial reverse remodeling and thereby contributing to improvement of left ventricular systolic function.

Cocoa flavanols alleviate early diastolic dysfunction by decreasing left atrial volume in healthy elderly individuals

Abstract Background Enlargement of the left atrium (LA) predicts future cardiovascular events. Current guidelines recommend cocoa flavanol (CF) intake as it provides cardiovascular and metabolic benefits, although underlying mechanisms are not fully revealed. In this study, we hypothesized that CF intake reverses LA enlargement as a surrogate marker for diastolic dysfunction in elderly individuals without cardiovascular diseases. Methods and Results In a randomized, double-blinded trial, we investigated the effects of CF on systolic and diastolic heart function in healthy elderly individuals. Precise assessment of left-atrial and left-ventricular volume as well as strain rates, all together as emblems of early subclinical cardiac impairment, and markers of systolic function were measured by high-resolution cardiac magnetic resonance (CMR) imaging before and after CF intake. Sixty-three participants (59% male) aged ≥ 55 years received either 500 mg CF (n=30) or a placebo (n=33) twice daily for 30 days. CF counteracted subclinical cardiac dysfunction, evidenced by a reduction in maximal LA volume and LA volume index by 12.6±3.5% (p=0.0063 and p=0.0067) and LV end-diastolic volume (LVEDV) and LVEDV index by ~4.9±1.9% (p=0.049 and p=0.0413). CF intake did not influence strain, strain rate, and systolic function parameters, while the systolic blood pressure decreased by 7 mmHg [~4.7±1.9% (p=0.04)]. Conclusion We provide evidence that CF intake mitigates early changes of diastolic dysfunction and improves cardiovascular health by reversing left atrial and left ventricular remodeling. Cocoa flavanol consumption may prevent age-related cardiac changes in healthy elderly individuals and promote a health span free from cardiovascular diseases.

Echocardiographic evaluation of cardiac remodelling in a cohort of patients with heart failure and reduced ejection fraction treated with dapagliflozin

Abstract Background Several mechanisms have been proposed to explain SGLT2 inhibitors’ (SGLT2i) beneficial effects in patients with heart failure (HF), but their exact mode of action in this setting is not fully understood. Pivotal randomised clinical trials regarding this class of drugs in HF setting have not reported echocardiographic data regarding potential cardiac positive remodelling. Objectives To assess the effects of dapagliflozin treatment initiation on cardiac remodelling in patients with HF and reduced ejection fraction (HFrEF), with a focus on left ventricular performance and atrial volumetry. Methods In this retrospective observational study, we analysed data from 94 patients with HFrEF in whom dapagliflozin had been prescribed as part of HF treatment optimization. Inclusion criteria were: age > 18 years; ongoing optimal medical therapy (OMT) for HF according to 2021 ESC HF guidelines (except for SGLT2i); transthoracic echocardiogram within 30 days of baseline assessment demonstrating a left ventricular (LV) ejection fraction (EF) <40%; comprehensive assessment at 6 months with clinical, laboratory and echocardiographic data. Results Patients (mean age 71.7 ± 9.8, 76% males, coronary artery disease as HFrEF main aetiology in 66%) showed significant cardiac remodelling after dapagliflozin initiation, specifically in terms of stroke volume index (SVi, +9.7 ml/m2, p<0.001), LVEF (+5.1%, p<0.001), LV end-diastolic volume (LV EDV) index (-8.4 ml/m2, p<0.001), left atrial (LA) volume index (-3.9 ml/m2, p=0.026), and LV mass index (LVMi, -12.9 gr/m2, p=0.004). BNP tended to significantly decrease (-168.6 ng/L, p=0.025). Percentage of patients with an indication for ICD implantation in primary prevention went from 36.2% to 8.5%, p<0.001. We did not observe significant differences in terms of mitral regurgitation (MR) grading at follow-up (in particular, the proportion of patients with severe MR remained approximately stable: 7% vs 4%, p=0.86). We did not observe any change in diastolic function measured by E/e’ ratio (mean difference -0.6; 95% CI -2.2 to 0.9, p=0.41). Conclusions Treatment with dapagliflozin resulted in positive remodelling in our cohort of patients with HFrEF in terms of chamber volumes, contractility parameters (and this was not explained by an improvement in MR severity) and LVMi. There was a significant decrease in natriuretic peptide as well as in the proportion of patients with primary prevention ICD indication. Our findings highlight the need of further data to fully elucidate the exact mechanism that leads to LA and LV positive remodelling with SGLT2i.Figure 1.Change in TTE Parameters

Impact of adjacent thoracic structures in negative left atrial remodelling in atrial fibrillation

Abstract Background Previous work has suggested that compression from external structures can promote negative atrial remodelling in atrial fibrillation (AF) [1]. This is mechanistically plausible, with many recognised risk factors in developing AF (age, hypertension, obesity, obstructive sleep apnoea, etc.) related through activation of the autonomic nervous system with an associated increase in atrial pressure and chronic elevation in wall stress [2,3]. Such negative remodelling contributes to the existence of arrhythmogenic atrial substrate [4]. This is highly significant when we consider catheter ablation of extrapulmonary vein targets. Purpose This study aims to investigate the relationship between abnormal conduction patterns indicative of potential AF drivers and their proximity to structures adjacent to the left atrium (LA). Methods Eight patients with paroxysmal or persistent AF, scheduled for an elective catheter ablation procedure using a charge density mapping (CDM) system [5] underwent pre-procedural cardiac MRI. 3D surface mesh reconstructions of individuals’ LA and adjacent structures (ascending aorta [AoA], descending aorta [AoD], and spine) were produced from 2D MRI slices using a proprietary graphical interface tool developed in MATLAB (Figure 1A & B) [6]. MRI derived LA geometries were registered with their CDM counterparts by the Iterative Closest Point algorithm (Figure 1C); this enabled integration of MRI LA geometries into the CDM system. Subsequently, non-contact intrachamber voltage measurements from individuals’ procedures were used to derive cardiac activation directly onto MRI LA geometries. Abnormal conduction patterns representing possible AF drivers (focal firing, rotational propagation, and pivoting propagation) [5] were quantified as occurrences per second at each vertex of MRI LA geometries (Figure 1D). These conduction patterns could then be visualised and assessed in the context of adjacent structures (Figure 1E), with the Euclidean distance between each vertex of the MRI LA geometries and the closest point to their adjacent structures being calculated. Results Mean age was 65±9 years; 4 patients (50%) were male; AF was paroxysmal in 3 (37%) and persistent in 5 (63%); median time since AF diagnosis was 1 (1-3.8) years; ablation type was de novo in 5 (63%) and retreatment in 3 (38%). Frequencies of pivoting and rotational propagation were notably higher in regions of the LA closer to the AoA, and lower near the AoD and spine (Figure 2A & B). Conversely, focal firing showed a less prominent trend, being more frequent in LA regions nearer the AoD and distant from the AoA (Figure 2C). Conclusions Compression from the ascending aorta may promote anterior LA remodelling in AF, leading to increased pivoting and rotational AF drivers. Clinically, this suggests a potential target for ablation therapy with an anterior seatbelt line connecting the right superior pulmonary vein to the mitral annulus.

Left atrioventricular coupling index is an independent associate of new-onset AF and stroke in hypertrophic cardiomyopathy: a CMR study

Abstract Background Left atrial (LA) dysfunction is an important marker of disease progression in hypertrophic cardiomyopathy (HCM). LA volumes and functional parameters are associated with new-onset atrial fibrillation (AF) and its complications including stroke. The association between left atrioventricular coupling (LACI), a parameter reflecting the contribution of the left ventricular and LA remodeling to LA dysfunction, with the occurrence of new-onset AF and stroke has not been evaluated. Aim To investigate the association between LACI and the occurrence of new-onset AF or stroke in patients with HCM. Methods In patients with an established diagnosis of HCM and cardiac magnetic resonance (CMR) data, LACI was calculated as the ratio between the LA and the LV end-diastolic volumes. New-onset AF or occurrence of stroke comprised the primary combined endpoint. Cumulative event-free survival rates for the occurrence of the primary endpoint were estimated with the population divided according to a LACI cut-off value of 40%. The association between clinical and CMR variables and the primary endpoint was assessed with univariable and multivariable Cox proportional hazard regression models. Results Of 114 patients with HCM, (mean age 54±16 years, 33 (29%) female, LV ejection fraction 67.0±8.4%), 71 patients (49%) had a LACI > 40% (left atrioventricular uncoupling). During a median follow-up of 4.1 (1.8-6.4) years, 19 (16.7%) patients experienced new-onset AF or stroke. Patients with preserved left atrioventricular coupling (LACI ≤ 40%) had a lower cumulative rate of events compared to those with left atrioventricular uncoupling (log-rank p=0.031, Fig. 1). LACI was independently associated with new-onset AF or stroke after adjusting by the presence of late gadolinium enhancement (LGE) sex and age (HR=23.27, p=0.016). Conclusions In patients with HCM, the presence of left atrioventricular uncoupling is independently associated with the occurrence of new-onset AF or stroke.

Effect of radiofrequency ablation on improving cardiac structure and function in patients with atrial fibrillation and functional mitral regurgitation

Objective: Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone. Methods: This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups. Results: After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm2 vs. (-3.55±2.50) cm2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e' (ΔE/e':-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion: Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.

Clinical relevance of left atrial structural remodeling and non-pulmonary vein foci in atrial fibrillation.

The mechanistic role of left atrial (LA) structural remodeling as a non-pulmonary vein (PV) trigger in the initiation of atrial fibrillation (AF) remains uncertain. This study is aimed at prospectively evaluating the association between non-PV triggers and LA structural remodeling. A total of 517 patients undergoing catheter ablation for AF were included. After PV isolation, a standardized protocol was implemented to reveal non-PV triggers, which included burst pacing into AF followed by cardioversion during isoproterenol infusion. If pacing-induced atrial tachycardia (AT) was observed, mapping and catheter ablation were performed. The mean percentage of LA low-voltage area (LVA) < 0.5mV incrementally increased during right atrial pacing among the no induction (n = 470), AF (n = 21), and AT (n = 26) groups (2.6 ± 5.7%, 5.5 ± 6.4%, and 18.0 ± 21.5%, respectively; P < 0.001). In the AF induction group, non-PV foci originated from the left atrium in 13 of 25 foci (52%), and 8 of 13 LA non-PV foci (62%) were located in the septal region. All except 1 focus originated from the non-LVA < 0.5mV (8%), but 8 of the 13 LA foci originated from the LVA < 1.0mV (62%). There were no differences in AF recurrence among the groups (log-rank, P = 0.160). The majority of non-PV foci in the LA originated outside regions with advanced structural remodeling, thus suggesting the limited effectiveness of adjunctive ablation guided by the LVA < 0.5mV during sinus rhythm in eliminating non-PV triggers.

Cardiac remodelling in patients with atrial fibrillation and obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) can cause left atrial (LA) and left ventricular (LV) remodelling, which is linked to atrial fibrillation (AF). Whether continuous positive airway pressure (CPAP) can reverse LA and LV remodelling in patients with OSA and paroxysmal AF (PAF) has yet to be studied. We assessed the impact of CPAP treatment on LA and LV size and function in patients with OSA and PAF before and after catheter ablation. In a randomised controlled trial, we screened patients with PAF for OSA. We enrolled patients with an Apnoea-Hypopnoea Index ≥15/hour. The burden of AF was monitored by an implantable loop recorder in all patients. Patients were then randomised to CPAP treatment or standard care. Transthoracic echocardiography was performed at baseline and after 6 and 12 months to assess LV and LA function and remodelling with advanced echocardiographic imaging techniques. We enrolled 109 patients (63±7 years, body mass index 29.6±4.3, 76% men). 83 patients were scheduled for pulmonary vein isolation (PVI) and 26 for clinical follow-up only. 55 patients were randomised to CPAP and 54 to standard care. The burden of AF decreased significantly in patients who underwent PVI irrespective of treatment with CPAP (p for difference ≤0.001). Patients in the study group had LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) within the normal range, increased LA Volume Index (LAVI), LA volume (by speckle tracking) and decreased LA reservoir strain at baseline. We did not observe any improvement in LVEF, GLS, LAVI, LA volume or LA reservoir strain in either group during the 12 months of follow-up. In patients with PAF and OSA, treatment with CPAP was not associated with reverse LA remodelling within 12 months of follow-up.

Detection of Left Atrial Remodeling by Three-Dimensional Echocardiography in Symptomatic Patients Known to Had Non-Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is one of the most prevalent inherited disorders and a common cause of sudden heart death. Left atrial (LA) dilatation frequently occurs in patients with HCM as a result of impaired left ventricular (LV) relaxation or associated involvement of LA myocardium in HCM. We enrolled 170 patients known to had HCM (non-obstructive type) and 30 healthy subjects (control group). All of them underwent two-dimensional (2D) echocardiography to measure LV dimensions, function, LA dimension, LA deformations, pulmonary artery pressure (PAP) and LV global longitudinal strain (LVGLS). LA volumes and mechanics were also measured by three-dimensional (3D) echocardiography. By 2D echocardiography, patient group revealed significantly lower all LA functions vs. control group including reservoir (26 ± 4 vs. 43 ± 3, P < 0.001), conduit (-14 ± 2 vs. -25 ± 2, P < 0.001), and booster pump functions (-12 ± 2 vs. -18 ± 1, P < 0.001). PAP was significantly higher in patient group (42 ± 7 vs. 27 ± 4 in control group). LVGLS was significantly lower in patient group (-15±1.4% vs. -23±2% in control group). Using 3D speckle tracking echocardiography (STE), there were a significantly higher indexed maximum LA volume (Vmax indexed) (43.5 ± 5.6 vs. 28.7 ± 3.7, P < 0.001), but significantly lower left atrial strain at reservoir function (LASr) (24 ± 4 vs. 41 ± 3, P < 0.001), left atrial strain at conduit function (LAScd) (-13 ± 2 vs. -24 ± 2, P < 0.001), and left atrial strain at contractile function (LASct) (-11 ± 2 vs. -18 ± 1, P < 0.001). Three-dimensional transthoracic echocardiography (TTE) is a feasible method for the assessment of LA remodeling, but there is adverse LA remodeling in patients with long-standing non-obstructive HCM including impaired all LA mechanics and with increased septal thickness, there are more diastolic dysfunction and more reduction of LA mechanics.

Machine Learning Algorithm to Predict Atrial Fibrillation Using Serial 12-Lead ECGs Based on Left Atrial Remodeling.

We hypothesized that analysis of serial ECGs could predict new-onset atrial fibrillation (AF) more accurately than analysis of a single ECG by detecting the subtle cardiac remodeling that occurs immediately before AF occurrence. Our aim in this study was to compare the performance of 2 types of machine learning (ML) algorithms. Standard 12-lead ECGs of patients selected by cardiologists between January 2010 and May 2021 were used for ML model development. Two ML models (single ECG and serial ECG) were developed using a light gradient boosting machine-learning algorithm. Model performance was evaluated based on the area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, and F1 score. We trained the ML models on 415 964 ECGs from 176 090 patients. When testing the 2 ML models using external validation data sets, the performance of the serial-ML model was significantly better than that of the single-ML model for predicting new-onset AF (single- versus serial-ML model: sensitivity 0.744 versus 0.810; specificity 0.742 versus 0.822; accuracy 0.743 versus 0.816; F1 score 0.743 versus 0.815; area under the receiver operating characteristic curve 0.812 versus 0.880; P<0.001). The Shapley Additive Explanations analysis ranked P-wave duration and amplitude among the top 10 ECG parameters. An ML model based on serial ECGs from an individual had greater ability to predict new-onset AF than the ML model based on a single ECG. P-wave morphologies were associated with future AF prediction.

Kynurenines in heart failure with preserved ejection fraction: an influence of type 2 diabetes.

Given their association with inflammatory processes and oxidative stress, tryptophan metabolites involved in the kynurenine pathway (KP) play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D). The study aimed to examine the relationship between the parameters of HFpEF, as determined by transthoracic echocardiography, and metabolites of the KP. We prospectively included 120 patients with HFpEF, 60 with and 60 without T2D, and 55 controls. High‑performance liquid chromatography was used to quantify the serum metabolites of KP. Echocardiography was used to assess left ventricular systolic and diastolic function. The patients with HFpEF and T2D showed an increase in tryptophan, kynurenine, and anthranilic acid concentrations (P = 0.001, P <0.001, and P <0.001, respectively) with a concomitant decrease in 3‑hydroxykynurenine (P <0.001) and quinolinic acid (P = 0.003), as compared with those with HFpEF without T2D. Left ventricular and left atrial remodeling was more pronounced in the group with T2D, but differences between these parameters did not reach statistical significance. Left ventricular global longitudinal strain was lower in the subgroup of patients with HFpEF and T2D than in the subgroup without T2D (P = 0.003). The study showed altered tryptophan metabolism in patients with HFpEF, highlighting a possible connection. The findings suggest potential implications for targeted therapeutic strategies focusing on tryptophan metabolism and cardiac function in patients with HFpEF and T2D.

Mavacamten-Associated Temporal Changes in Left Atrial Function in Obstructive HCM: Insights From the VALOR-HCM Trial

BackgroundIn severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) trial showed that mavacamten reduced the eligibility for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients. Mavacamten also resulted in favorable cardiac remodeling, including improvement in biomarkers (eg, N-terminal pro–B-type natriuretic peptide and troponin T). However, the impact of mavacamten on left atrial (LA) function is unknown. ObjectivesThe aim of this study was to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial. MethodsVALOR-HCM included 112 symptomatic patients with obstructive HCM (mean age 60 years; 51% male). Patients assigned to receive mavacamten at baseline (n = 56) continued therapy for 56 weeks and those assigned to placebo transitioned to mavacamten (n = 52) from week 16 to week 56. Echocardiographic LA strain (reservoir, conduit, and contraction) was measured by using a vendor-neutral postprocessing software. ResultsAt baseline, the mean LA volume index (LAVI) and LA strain values (conduit, contraction, and reservoir) were 41.3 ± 16.5 mL/m2, −11.8% ± 6.5%, −8.7% ± 5.0%, and 20.5% ± 8.7%, respectively (all worse than reported normal). LAVI significantly improved by −5.6 ± 9.7 mL/m2 from baseline to week 56 (P < 0.001). There was a significant (P < 0.05) improvement in absolute LA strain values from baseline to week 56 (conduit [−1.7% ± 6%], contraction [−1.2% ± 4.5%], and reservoir [2.8% ± 7.7%]). Patients originally receiving placebo had no differences in LA measurements up to week 16. There was no significant improvement in LA strain values (conduit [−0.9% ± 3.8%], contraction [−0.4% ± 3.4%], and reservoir [1.4% ± 6.1%]; all; P = NS) from baseline to week 56 in patients with history of atrial fibrillation. ConclusionsIn VALOR-HCM, mavacamten resulted in an improvement in LAVI and LA strain at week 56, suggesting sustained favorable LA remodeling and improved function, except in the atrial fibrillation subgroup. Whether the advantageous LA remodeling associated with long-term treatment with mavacamten results in a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM remains to be proven. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072)

Management of Left Atrial Tachyrhythms in the Setting of HFpEF with Pulsed-Field Ablation: Treating Fire with Water?

Atrial fibrillation (AF) in the setting of heart failure (HF) with preserved ejection fraction (HFpEF) is a prevalent comorbidity and is enabled by adverse left atrial (LA) remodeling, dilation, and scar tissue formation. These changes are facilitated by poor left ventricular compliance. A growing body of clinical evidence and medical guidelines suggest that managing atrial tachyrhythms with catheter ablation (CA) is paramount to treating concomitant HF. This recommendation is complicated in that thermal CA modalities, namely radiofrequency ablation and cryoablation, are both therapeutic via inducing additional scar tissue. AF treatment with thermal CA may compound the atrial scar burden for patients who already have extensive scars secondary to HFpEF. Therefore, thermal CA could act as "gasoline" to the slowly burning "fire" within the LA, increasing the rate of AF recurrence. Pulsed-field ablation (PFA), which utilizes high-voltage irreversible electroporation, is a non-thermal CA technique that is capable of disrupting reentrant microcircuits and arrhythmogenic foci without inducing significant scar burden. PFA has the potential to mitigate the strong fibrosis response to thermal CA that predisposes to AF by serving as "water" rather than "gasoline". Thus, PFA may increase the efficacy and durability of CA for AF in HFpEF, and subsequently, may decrease the risk of procedural complications from repeat CAs. In this article, we provide a summary of the clinical concepts underlying HFpEF and AF and then summarize the data to date on the potential of PFA being a superior CA technique for AF in the setting of comorbid HFpEF.

Changes in epicardial adipose tissue volume before and after cryoballoon ablation in patients with atrial fibrillation: Supporting the “AF begets EAT” theory

BackgroundEpicardial adipose tissue (EAT) is closely associated with atrial fibrillation (AF), suggesting that it may be 1 of the causes of AF progression. However, it is unclear whether AF affects EAT. ObjectiveThis study aimed to demonstrate that sinus rhythm restoration reduces EAT volume (EATV) through left atrial reverse remodeling (LARR). MethodsWe analyzed data from 247 patients who underwent cryoballoon ablation for AF. EATV was assessed by contrast-enhanced computed tomography with a 3-dimensional analysis workstation, evaluating EATV surrounding the entire heart (total-EATV) and left atrium (LA-EATV) at baseline and 6 months after cryoballoon ablation. ResultsAt 6 months, all patients but 1 with persistent AF were in sinus rhythm. Total-EATV and LA-EATV were both significantly decreased in patients with persistent AF (n = 33; total-EATV: 148.8 ± 53.3 mL to 142.9 ± 53.5 mL [P = .01]; LA-EATV: 26.8 ± 11.3 mL to 25.2 ± 10.7 mL [P = .01]). No changes were observed in patients with paroxysmal AF (n = 214). Persistent AF was more strongly associated with LARR than paroxysmal AF (odds ratio, 2.34; 95% confidence interval, 1.01–5.44; P = .05). LARR showed an independent correlation with both total-EATV and LA-EATV reduction (odds ratio, 1.78 [P = .04] and 2.80 [P < .001], respectively). ConclusionThese findings suggest a novel “AF begets EAT” theory, complementing the previously accepted role of EAT as a cause of AF and supporting the “AF begets AF” mechanism.