Exploring Changes in Myocyte Structure, Contractility, and Energetics From Mechanical Unloading in Patients With Heart Failure Undergoing Ventricular Assist Device Implantation: A Systematic Review and Meta-Analysis.

AIMS: Recent reports of myocardial recovery after mechanical unloading with left ventricular assist devices (LVADs) have challenged the prevailing notion that end-stage heart failure (HF) is irreversible. To improve our understanding of this phenomenon, we comprehensively analysed the structural, functional, and energetic changes in failing human cardiomyocytes after LVAD implantation. METHODS: Based on a prospectively registered protocol (PROSPERO-CRD42022380214), 30 eligible studies were identified from 940 records with a pooled population of 648 patients predominantly with non-ischaemic cardiomyopathy. RESULTS: LVAD led to a substantial regression in myocyte size similar to that of donor hearts (standardised mean difference, -1.29; p<0.001). The meta-regression analysis revealed that HF duration was a significant modifier on the changes in myocyte size. There were some suggestions of fibrosis reversal (-5.17%; p=0.009); however, this was insignificant after sensitivity analysis. Developed force did not improve in cardiac trabeculae (n=5 studies); however, non-physiological isometric contractions were tested. At the myocyte level (n=4 studies), contractile kinetics improved where the time-to-peak force reduced by 41.7%-50.7% and time to 50% relaxation fell by 47.4%-62.1% (p<0.05). Qualitatively, LVAD enhanced substrate utilisation and mitochondrial function (n=6 studies). Most studies were at a high risk of bias. CONCLUSION: The regression of maladaptive hypertrophy, partial fibrosis reversal, and normalisation in metabolic pathways after LVAD may be a testament to the heart's remarkable plasticity, even in the advanced stages of HF. However, inconsistencies exist in force-generating capabilities. Using more physiological force-length work-loop assays, addressing the high risks of bias and clinical heterogeneity are crucial to better understand the phenomenon of reverse remodelling.

Left ventricular mass predicts cardiac reverse remodelling in patients treated with empagliflozin.

BACKGROUND: The cardiovascular (CV) benefits of sodium-glucose transport protein 2 inhibitors have been attributed, in part, to cardiac reverse remodelling. The EMPA-HEART CardioLink-6 study reported that sodium-glucose cotransporter-2 inhibition for 6 months with empagliflozin was associated with a significant reduction in left ventricular mass indexed to body surface area (LVMi). In this sub-analysis, we evaluated whether baseline LVMi may influence how empagliflozin affects cardiac reverse remodelling. METHODS: A total of 97 patients with type 2 diabetes and coronary artery disease were randomized to empagliflozin (10 mg/d) or matching placebo for 6 months. The study cohort was divided into those whose baseline LVMi was ≤ 60 g/m2 and those who had a baseline LVMi > 60 g/m2. Subgroup comparisons were conducted using a linear regression model adjusted for baseline values (ANCOVA) that included an interaction term between LVMi subgroup and treatment. RESULTS: Baseline LVMi was 53.3 g/m2 (49.2-57.2) and 69.7 g/m2 (64.2-76.1) for those with baseline ≤ 60 g/m2 (n = 54) and LVMi > 60 g/m2 (n = 43) respectively. The adjusted difference of LVMi regression between those randomized to empagliflozin and placebo were - 0.46 g/m2 (95% CI: -3.44, 2.52, p = 0.76) in the baseline LVMi ≤ 60 g/m2 subgroup and - 7.26 g/m2 (95% CI: -11.40, -3.12, p = 0.0011) in the baseline LVMi > 60 g/m2 subgroup (p-for-interaction = 0.007). No significant associations were found between baseline LVMi and 6-month change in LV end systolic volume-indexed (p-for-interaction = 0.086), LV end diastolic volume-indexed (p-for-interaction = 0.34), or LV ejection fraction (p-for-interaction = 0.15). CONCLUSIONS: Patients with higher LVMi at baseline experienced greater LVM regression with empagliflozin.

Prevalence of glucose metabolism disorders and its association with left atrial remodelling before and after catheter ablation in patients with atrial fibrillation.

AIMS: To investigate the exact prevalence of glucose metabolism disorders, and their impact on left atrial (LA) remodelling and reversibility in patients with atrial fibrillation (AF). METHODS AND RESULTS: We examined 204 consecutive patients with AF who underwent their first catheter ablation (CA). Oral glucose tolerance test was used to evaluate glucose metabolism disorders in 157 patients without known diabetes mellitus (DM). Echocardiography was performed before and 6 months after CA. Oral glucose tolerance test identified abnormal glucose metabolism in 86 patients [11 with newly diagnosed DM, 74 with impaired glucose tolerance (IGT) and 1 with impaired fasting glucose (IFG)]. Ultimately, 65.2% of patients had abnormal glucose metabolism. Diabetes mellitus group had the worst LA reservoir strain and LA stiffness (both P < 0.05), while there was no significant difference in baseline LA parameters between normal glucose tolerance (NGT) group and IGT/IFG group. The prevalence of LA reverse remodelling (≥15% decrease in the LA volume index at 6 months after CA) was significantly higher in NGT group compared with IGT/IFG and DM group (64.1 vs. 38.6 vs. 41.5%, P = 0.006). Both DM and IFG/IGT carry a significant risk of lack of LA reverse remodelling independent of baseline LA size and AF recurrence. CONCLUSION: Approximately 65% of patients with AF who underwent their first CA had abnormal glucose metabolism. Patients with DM had significantly impaired LA function compared with non-DM patients. Impaired glucose tolerance/IFG as well as DM carries significant risk of unfavourable LA reverse remodelling. Our observations may provide valuable information regarding the mechanisms and therapeutic strategies of glucose metabolism-related AF.

Prediction of Left Ventricular Reverse Remodelling: A Mini Review on Clinical Aspects.

Improvement of left ventricular ejection fraction (LVEF) in patients after the first manifestation of heart failure with reduced ejection fraction (HFrEF) has currently been observed more frequently than it was years ago. This appears to be due to the early initiation of comprehensive HF therapy. According to these observations, a new HF syndrome category, heart failure with improved ejection fraction (HFimpEF), was introduced. In this short review, we present definitions of reverse remodelling, myocardial remission, and myocardial recovery. We provide an overview of clinical research aimed at evaluating reverse remodelling in different populations of patients with HFrEF. Clinical and imaging characteristics and biomarkers identified as predictors of reverse remodelling and improvement of the LVEF are discussed. We also briefly address the current views on the management of patients with HFimpEF. In-depth study and knowledge of the molecular mechanisms underlying the reverse remodelling process may lead to the identification of new individualized therapeutic approaches for HFrEF.

Transcriptomic Signatures of End-Stage Human Dilated Cardiomyopathy Hearts with and without Left Ventricular Assist Device Support.

Left ventricular assist device (LVAD) use in patients with dilated cardiomyopathy (DCM) can lead to a differential response in the LV and right ventricle (RV), and RV failure remains the most common complication post-LVAD insertion. We assessed transcriptomic signatures in end-stage DCM, and evaluated changes in gene expression (mRNA) and regulation (microRNA/miRNA) following LVAD. LV and RV free-wall tissues were collected from end-stage DCM hearts with (n = 8) and without LVAD (n = 8). Non-failing control tissues were collected from donated hearts (n = 6). Gene expression (for mRNAs/miRNAs) was determined using microarrays. Our results demonstrate that immune response, oxygen homeostasis, and cellular physiological processes were the most enriched pathways among differentially expressed genes in both ventricles of end-stage DCM hearts. LV genes involved in circadian rhythm, muscle contraction, cellular hypertrophy, and extracellular matrix (ECM) remodelling were differentially expressed. In the RV, genes related to the apelin signalling pathway were affected. Following LVAD use, immune response genes improved in both ventricles; oxygen homeostasis and ECM remodelling genes improved in the LV and, four miRNAs normalized. We conclude that LVAD reduced the expression and induced additional transcriptomic changes of various mRNAs and miRNAs as an integral component of the reverse ventricular remodelling in a chamber-specific manner.

Mechanisms underlying the pathophysiology of heart failure with preserved ejection fraction: the tip of the iceberg.

Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with a complex aetiology often associated with several comorbidities, such as left ventricle pressure overload, diabetes mellitus, obesity, and kidney disease. Its pathophysiology remains obscure mainly due to the complex phenotype induced by all these associated comorbidities and to the scarcity of animal models that adequately mimic HFpEF. Increased oxidative stress, inflammation, and endothelial dysfunction are currently accepted as key players in HFpEF pathophysiology. However, we have just started to unveil HFpEF complexity and the role of calcium handling, energetic metabolism, and mitochondrial function remain to clarify. Indeed, the enlightenment of such cellular and molecular mechanisms represents an opportunity to develop novel therapeutic approaches and thus to improve HFpEF treatment options. In the last decades, the number of research groups dedicated to studying HFpEF has increased, denoting the importance and the magnitude achieved by this syndrome. In the current technological and web world, the amount of information is overwhelming, driving us not only to compile the most relevant information about the theme but also to explore beyond the tip of the iceberg. Thus, this review aims to encompass the most recent knowledge related to HFpEF or HFpEF-associated comorbidities, focusing mainly on myocardial metabolism, oxidative stress, and energetic pathways.

The Degree of Cardiac Remodelling before Overload Relief Triggers Different Transcriptome and miRome Signatures during Reverse Remodelling (RR)-Molecular Signature Differ with the Extent of RR.

This study aims to provide new insights into transcriptome and miRome modifications occurring in cardiac reverse remodelling (RR) upon left ventricle pressure-overload relief in mice. Pressure-overload was established in seven-week-old C57BL/6J-mice by ascending aortic constriction. A debanding (DEB) surgery was performed seven weeks later in half of the banding group (BA). Two weeks later, cardiac function was evaluated through hemodynamics and echocardiography, and the hearts were collected for histology and small/bulk-RNA-sequencing. Pressure-overload relief was confirmed by the normalization of left-ventricle-end-systolic-pressure. DEB animals were separated into two subgroups according to the extent of cardiac remodelling at seven weeks and RR: DEB1 showed an incomplete RR phenotype confirmed by diastolic dysfunction persistence (E/e' ≥ 16 ms) and increased myocardial fibrosis. At the same time, DEB2 exhibited normal diastolic function and fibrosis, presenting a phenotype closer to myocardial recovery. Nevertheless, both subgroups showed the persistence of cardiomyocytes hypertrophy. Notably, the DEB1 subgroup presented a more severe diastolic dysfunction at the moment of debanding than the DEB2, suggesting a different degree of cardiac remodelling. Transcriptomic and miRomic data, as well as their integrated analysis, revealed significant downregulation in metabolic and hypertrophic related pathways in DEB1 when compared to DEB2 group, including fatty acid ß-oxidation, mitochondria L-carnitine shuttle, and nuclear factor of activated T-cells pathways. Moreover, extracellular matrix remodelling, glycan metabolism and inflammation-related pathways were up-regulated in DEB1. The presence of a more severe diastolic dysfunction at the moment of pressure overload-relief on top of cardiac hypertrophy was associated with an incomplete RR. Our transcriptomic approach suggests that a cardiac inflammation, fibrosis, and metabolic-related gene expression dysregulation underlies diastolic dysfunction persistence after pressure-overload relief, despite left ventricular mass regression, as echocardiographically confirmed.

Electrocardiographic optimization techniques in resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a cornerstone of therapy for patients with heart failure, reduced left ventricular (LV) ejection fraction, and a wide QRS complex. However, not all patients respond to CRT: 30% of CRT implanted patients are currently considered clinical non-responders and up to 40% do not achieve LV reverse remodelling. In order to achieve the best CRT response, appropriate patient selection, device implantation, and programming are important factors. Optimization of CRT pacing intervals may improve results, increasing the number of responders, and the magnitude of the response. Echocardiography is considered the reference method for atrioventricular and interventricular (VV) intervals optimization but it is time-consuming, complex and it has a large interobserver and intraobserver variability. Previous studies have linked QRS shortening to clinical response, echocardiographic improvement and favourable prognosis. In this review, we describe the electrocardiographic optimization methods available: 12-lead electrocardiogram; fusion-optimized intervals (FOI); intracardiac electrogram-based algorithms; and electrocardiographic imaging. Fusion-optimized intervals is an electrocardiographic method of optimizing CRT based on QRS duration that combines fusion with intrinsic conduction. The FOI method is feasible and fast, further reduces QRS duration, can be performed during implant, improves acute haemodynamic response, and achieves greater LV remodelling compared with nominal programming of CRT.

Biomarkers to predict the response to cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an established non-pharmacological treatment for selected heart failure patients with wide QRS duration. However, there is a persistent number of non-responders throughout. The prediction of the CRT response is paramount to adequately select the correct patients for CRT. One of the expanding fields of research is the development of biomarkers that predict the response to CRT. A review of the available literature on biomarkers in CRT patients has been performed to formulate a critical appraisal of the available data. The main conclusion of our review is that biomarker research in this patient population is very fragmented and broad. This results in the use of non-uniform endpoints to define the CRT response, which precludes an in-depth comparison of the available data. To improve research development in this field, a uniform definition of the CRT response and relevant endpoints is necessary to better predict the CRT response.

Effect of Continuous-Flow Mechanical Circulatory Support on Microvasculature Remodeling in the Failing Heart.

Left ventricle (LV) unloading caused by a left ventricular assist device (LVAD) has been shown to enhance reverse LV remodeling in end-stage cardiomyopathy. Several reports consistently suggest that a pulsatile-flow LVAD has more profound effects compared to continuous-flow LVAD, though the responsible mechanisms are not fully understood. We hypothesized that arterial pulsatility, being affected by the type of LVAD, may affect microvasculature and functional/pathological LV remodeling in end-stage cardiomyopathy. The study included 18 patients with chronic heart failure who underwent LVAD implantation. Eight patients were implanted with pulsatile-flow LVAD, and 10 patients were implanted with continuous-flow LVAD. The results of serial echocardiograms and histopathological assessment of transmural LV tissues, which were collected during the implantation and removal of LVADs, were compared between the groups. The results of echocardiography showed that LV systolic dimension and LV ejection fraction improved greatly in the pulsatile-flow LVAD group compared to the continuous-flow LVAD group. Histological analysis showed that in both groups, increased microvasculature density and decreased cardiomyocyte size during LVAD support had no significant difference. In contrast, only the patients with continuous-flow LVADs had presented with significant increase in α-smooth muscle actin (α-SMA)-positive layer thickness and the number of proliferating cell nuclear antigen (PCNA)-positive cells of myocardial arterioles. We concluded that the use of long-term continuous-flow LVAD support, having less pulsatility, had induced more thickening to the medial layer of myocardial arterioles compared to the use of pulsatile-flow LVADs. Our findings suggest that the pathological impairment of myocardial microvascular structure during continuous-flow LVAD support may be a novel mechanism which accounts for the difference in LV remodeling depending on the type of LVAD.

Cardiac resynchronization therapy for patients with cardiac sarcoidosis.

Aims: Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. Methods and results: We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Conclusions: Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias.

Left Ventricular Mechanical Reverse Remodelling Not Followed by Electrical Reverse Remodelling: A Case Report.

Patients with severely depressed left ventricular ejection fractions (LVEFs) receive implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden death. However, in some patients, LVEFs may improve or even normalize over time, and these patients would no longer be qualified for ICD implantation based on the original criteria for which they have initially received an ICD. We report a patient with idiopathic dilated cardiomyopathy whose LVEF recovered to normal values after pharmacological therapy. Meanwhile, the patient had life-threatening ventricular fibrillation, aborted by the ICD. We reflect on the pathological features of left ventricular reverse remodelling and ventricular arrhythmogenesis, where the myocardial substrate appears to play an important role. Also, after LVEF improvement in a patient with a cardiac device, there is still a debate on whether we should perform a battery replacement.

A prospective study examining the role of myocardial Fibrosis in outcome following mitral valve repair IN DEgenerative mitral Regurgitation: rationale and design of the mitral FINDER study.

BACKGROUND: The optimal management of chronic severe primary degenerative mitral regurgitation (MR) is to repair the valve but identification of the optimal timing of surgery remains challenging. Current guidelines suggest 'watchful waiting' until the onset of symptoms or left ventricular (LV) dysfunction but these have been challenged as promoting 'rescue surgery'. Better predictors are required to inform decision-making in relation to the necessity and timing of surgery. Chronic volume overload is a stimulus for adverse adaptive LV remodelling. Subclinical reduction in LV strain before mitral repair predicts a fall in LV ejection fraction following surgery and is thought to reflect the development of myocardial fibrosis in response to chronic volume overload. Myocardial fibrosis can be detected non-invasively using cardiac magnetic resonance (CMR) imaging techniques as an expansion of the extracellular volume (ECV). METHODS/DESIGN: This study investigates whether: 1) patients with above median ECV will have smaller reduction in end-systolic volume index (as a measure of the degree of reverse LV remodelling) on CMR following mitral valve repair, compared to those with below median ECV; and 2) higher ECV on CMR, validated through histology, adversely impacts upon post-operative complications and symptomatic improvement following surgery. This is a multi-centre, prospective, cross-sectional comparison of patients prior to and 9 months following surgery for chronic severe primary degenerative MR. To establish the natural history of ECV in MR, an additional cohort of patients with asymptomatic MR who do not wish to consider early repair will be followed. Investigations include CMR, cardiopulmonary exercise test, stress echocardiography, signal-averaged electrocardiogram, 24-h electrocardiogram monitoring, laboratory tests and patient-reported outcome measures. Patients undergoing surgery will have cardiac biopsies performed at the time of mitral valve repair for histological quantification of fibrosis. DISCUSSION: This study will advance our understanding of ventricular remodelling in MR, its impact on patient symptoms and ventricular response following surgery. Establishing the link between myocardial fibrosis (measured on CMR and validated through histology), with early ventricular dysfunction, will offer physicians a novel non-invasive biomarker that can further inform the timing of surgery. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov ( NCT02355418 ) on 30th November 2015.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.

AIMS: Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. METHODS AND RESULTS: A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). CONCLUSION: Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase.

Predictors of left atrial volume index reduction following cryoballoon-based pulmonary vein isolation.

AIMS: Ablation for atrial fibrillation (AF) has been suggested to be associated with 'reverse left atrial remodelling'. Reduction in left atrial volume index (LAVIR) is regarded as a determinant of reverse remodelling following pulmonary vein isolation (PVI). However, there is paucity on data about the predictors for LAVIR after PVI. In this study, we aimed to investigate predictors of LAVIR at 12 months in AF patients undergoing cryoballoon-based PVI. METHODS AND RESULTS: Patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the recent consensus recommendations, were enrolled and followed-up for 12 months in this prospective observational study. Left atrial volume was derived using the biplane area-length method. A total of 160 patients (54.25 ± 7.66 years, 44.40% female) were involved in the study. Reduction in left atrial volume index occurred in 120 patients. Age [hazard ratio (HR): 0.901, 95% confidence interval (CI): 0.828-0.981, P = 0.017], hypertension (HR: 0.151, 95% CI: 0.048-0.471, P = 0.001), mild mitral regurgitation (MR) (HR: 5.327, 95% CI: 1.489-19.058, P = 0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005-0.065, P< 0.001) were found to be independent predictors for LAVIR. CONCLUSION: To the best of our knowledge, this is the largest study in the literature investigating the predictors of LAVIR following AF ablation. According to this data, younger patients without hypertension or moderate MR are most likely to experience LAVIR following ablation.

Atrial reverse remodelling is associated with outcome of cardiac resynchronization therapy.

AIMS: To study the prognostic effect of atrial reverse remodelling on outcome of cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Patients receiving a CRT device in the University Medical Centre Groningen were included. Atrial reverse remodelling was defined as a ≥10% reduction in left atrial volume index at 6-month follow-up. Success of CRT was defined as ventricular reverse remodelling with a reduction in left ventricular end-systolic volume of ≥15% at 6-month follow-up. Primary endpoint was all-cause mortality or heart failure hospitalizations. A total of 365 patients (mean age 65.1 ± 11.0 years, 73% men) were included; among them, 221 (61%) were in sinus rhythm and had no prior atrial fibrillation (AF), and 144 patients (39%) had a history of AF. During a mean follow up of 2.0 ± 1.0 years, 49 patients died. Cox regression analysis revealed that patients with no atrial and no ventricular reverse remodelling had the worst outcome (hazard ratio 3.1, 95% confidence interval 1.4-7.1, P = 0.006). Outcome in patients with only atrial reverse remodelling was comparable with outcome in patients with both atrial and ventricular reverse remodelling (hazard ratio 2.0, 95% confidence interval 0.7-5.6, P = 0.21). CONCLUSION: Patients without atrial and ventricular reverse remodelling have the worst outcome. Patients with only atrial reverse remodelling have improved left ventricular diastolic filling during follow-up and demonstrate a comparable outcome with patients with both atrial and ventricular reverse remodelling. Assessment of atrial reverse remodelling may provide additional prognostic information in determining CRT outcome.

Reversal of spherical remodelling of the left atrium after pulmonary vein isolation: incidence and predictors.

AIMS: Pulmonary vein isolation (PVI) induces left atrial (LA) volume reduction, known as reverse remodelling (RR). The related changes in LA shape have not yet been evaluated. Left atrial sphericity (LASP) is a new shape-based marker of remodelling that compares LA geometry and a perfect sphere and is a powerful predictor of PVI success. We aimed to evaluate the effect of PVI on LASP and describe the concept of spherical and volumetric RR. METHODS AND RESULTS: Left atrial sphericity and volume were automatically obtained with self-customized software using a magnetic resonance imaging-based three-dimensional reconstruction of LA. Reverse remodelling was defined as improvement in LASP (spherical RR) or volume reduction (volumetric RR). In a series of 102 patients, spherical and volumetric RR was observed in 42.2 and 69%, respectively. Patients with paroxysmal atrial fibrillation (AF) had higher probability to present spherical RR as compared with patients with persistent AF (50.8 vs. 29.3%, P = 0.03). Patients with persistent AF showed significant post-procedural worsening of LASP (81.9 vs. 82.9%, P = 0.04). Patients with no recurrence showed a trend towards a higher proportion of spherical RR compared with those with recurrences (46.2 vs. 32.4%, respectively); no differences were observed in volumetric RR (62.1 vs. 62.9%, respectively). Paroxysmal AF was the only independent predictor of spherical RR. CONCLUSION: Pulmonary vein isolation leads to spherical RR in a substantial proportion of patients, and in higher proportion of patients with paroxysmal AF. Reverse remodelling may be caused by a combination of scarring and myocardial structural recovery. Changes in LASP might be more specific than volume reduction to detect favourable remodelling.

Prognostic value of left atrial reverse remodelling in patients hospitalized with acute decompensated heart failure.

AIMS: Left atrial (LA) volume index (LAVI) in chronic heart failure (HF) predicts cardiovascular outcomes. However, the association between LAVI reduction during acute decompensated HF (ADHF) and its prognostic potential is limited. We hypothesized that LA reverse remodelling (LARR) after ADHF therapy would be associated with better clinical outcomes. METHODS: This retrospective study analysed clinical outcomes and the LAVI reduction rate of 363 out of 861 patients hospitalized for ADHF who underwent two-point echocardiography at admission and discharge between January 2015 and December 2019. The mean age was 74.3 ± 13.6 years, and the mean ejection fraction (EF) was 38.9 ± 15.2%. The follow-up echocardiogram was performed 13.0 [9.5, 20] days after admission. As the median LAVI reduction rate was 7.02%, the LARR was defined as an LAVI reduction rate >7%. RESULTS: During the 34.0 ± 20.2 months of follow-up, 117 patients (32.2%) reached the primary endpoint defined as cardiovascular death and rehospitalization for ADHF. Kaplan-Meier survival analysis showed that patients with LARR had a better prognosis. Multivariate analysis indicated that LARR was an independent predictor of cardiovascular events. Similar findings were observed in the subgroup analyses of patients with persistent/permanent atrial fibrillation and those with non-HF with reduced EF. Among patients who were brain natriuretic peptide (BNP) responders, defined as a relative reduction of >70% in BNP from admission to discharge, non-LARR was observed in 41.6%. BNP responders without LARR experienced worse prognoses. CONCLUSIONS: LARR in the early vulnerable phase after hospitalization for ADHF was associated with better long-term clinical outcomes.

Incidence and predictors of heart failure with improved ejection fraction category in a HFrEF patient population.

AIMS: The aim of the study was to assess the incidence and predictive factors of the development of heart failure with improved ejection fraction (HFimpEF) category during a 1 year follow-up period in a heart failure with reduced ejection fraction (HFrEF) patient population managed in a heart failure outpatient clinic. METHODS AND RESULTS: The study evaluated data from patients enrolled in the Hungarian Heart Failure Registry (HHFR). The incidence and predictive factors of the development of the HFimpEF category after 1 year follow-up were assessed in the group of patients who had HFrEF at baseline. We evaluated the incidence and predictors of the development of HFimpEF after a 1 year follow-up in relation to time since diagnosis of HFrEF in patients diagnosed within 3 months, between 3 months and 1 year, and beyond 1 year. The predictive factors of the development of HFimpEF were analysed using univariate and multivariate logistic regression analysis. Of the 833 HFrEF patients enrolled in the HHFR, the development of HFimpEF was observed in 162 patients (19.5%) during 1 year follow-up. In the whole patient population, independent predictors of the development of HFimpEF were female gender [odds ratio (OR): 1.73; 95% confidence interval (CI): 1.01-2.96; P < 0.05], non-ischaemic aetiology (OR: 1.95; 95% CI: 1.15-3.30; P < 0.05), and left ventricular end-diastolic diameter (LVEDD) <60 mm (OR: 2.04; 95% CI: 1.18-3.51; P < 0.05). The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The incidence of HFimpEF was 27.1% in patients diagnosed within 3 months, 18.4% in patients diagnosed between 3 months and 1 year, and 12.2% in patients diagnosed beyond 1 year. Non-ischaemic aetiology (OR: 4.76; 95% CI: 1.83-12.4; P < 0.01) and QRS width (OR: 0.81; 95% CI: 0.71-0.94; P < 0.01) for patients diagnosed within 3 months, LVEDD (OR: 0.54; 95% CI: 0.32-0.90; P < 0.05) and left atrial diameter ≤45 mm (OR: 5.44; 95% CI: 1.45-20.4; P < 0.05) for patients diagnosed between 3 months and 1 year, and LVEDD < 67 mm (OR: 2.71; 95% CI: 1.07-6.88; P < 0.05) for patients diagnosed beyond 1 year were found to be independent predictive factors. CONCLUSIONS: In our study, in this HFrEF patient population managed in a heart failure outpatient clinic, the 1 year incidence of HFimpEF was found to be ~20%. The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The most important predictors of the development of HFimpEF were female sex, non-ischaemic aetiology, narrower QRS width, and smaller diameter of the left ventricle and left atrium.