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Background: Although the "obesity paradox" is comprehensively elucidated in heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the role of body composition in left ventricular (LV) remodeling, LV reverse remodeling (LVRR), and clinical outcomes is still unclear for HF with mildly reduced ejection fraction (HFmrEF)., Methods: Our study is a single-centre, prospective, and echocardiography-based study. Consecutive HFmrEF patients, defined as HF patients with a left ventricular ejection fraction (LVEF) between 40 and 49%, between January 2016 to December 2021 were included. Echocardiography was re-examined at 3-, 6-, and 12-month follow-up to assess the LVRR dynamically. Body mass index (BMI), fat mass, fat-free mass, percent body fat (PBF), CUN-BAE index, and lean mass index (LMI) were adopted as anthropometric parameters in our study to assess body composition. The primary outcome was LVRR, defined as: (1) a reduction higher than 10% in LV end-diastolic diameter index (LVEDDI), or a LVEDDI < 33 mm/m 2 , (2) an absolute increase of LVEF higher than 10 points compared with baseline echocardiogram, or a follow-up LVEF ≥50%. The secondary outcome was a composite of re-hospitalization for HF or cardiovascular death., Results: A total of 240 HFmrEF patients were enrolled in our formal analysis. After 1-year follow-up based on echocardiography, 113 (47.1%) patients developed LVRR. Patients with LVRR had higher fat mass (21.7 kg vs. 19.3 kg, P = 0.034) and PBF (28.7% vs. 26.6%, P = 0.047) compared with those without. The negative correlation between anthropometric parameters and baseline LVEDDI was significant (all P < 0.05). HFmrEF patients with higher BMI, fat mass, PBF, CUN-BAE index, and LMI had more pronounced and persistent increase of LVEF and decline in LV mass index (LVMI). Univariable Cox regression analysis revealed that higher BMI (HR 1.042, 95% CI 1.002-1.083, P = 0.037) and fat mass (HR 1.019, 95% CI 1.002-1.036, P = 0.026) were each significantly associated with higher cumulative incidence of LVRR for HFmrEF patients, while this relationship vanished in the adjusted model. Mediation analysis indicated that the association between BMI and fat mass with LVRR was fully mediated by baseline LV dilation. Furthermore, higher fat mass (aHR 0.957, 95% CI 0.917-0.999, P = 0.049) and PBF (aHR 0.963, 95% CI 0.924-0.976, P = 0.043) was independently associated with lower risk of adverse clinical events., Conclusions: Body composition played an important role in the LVRR and clinical outcomes for HFmrEF. For HFmrEF patients, BMI and fat mass was positively associated with the cumulative incidence of LVRR, while higher fat mass and PBF predicted lower risk of adverse clinical events but not LMI., (© 2024. The Author(s).)

Partial or complete imaging resolution of left ventricular (LV) systolic dysfunction in patients with heart failure with reduced ejection fraction (HFrEF) has gone by many names in the past few decades, including LV recovery, remission, reverse remodeling, and, most recently, improvement. This phenomenon has been described in a variety of clinical scenarios, including removal of an acute myocardial insult, unloading with durable LV assist devices, and treatment with various devices as well as pharmacotherapies, termed guideline-directed medical therapy (GDMT). Irrespective of definition, systolic improvement is associated with improved clinical outcomes compared to persistent systolic dysfunction. In the past few years, systolic improvement has been distinguished from HFrEF as a new clinical entity referred to as HF with improved EF (HFimpEF). Given the relative novelty of this condition, there is a paucity of data with regard to the clinical trajectory and management of this population. In this review, we describe the history of myocardial improvement terminology and explore notable findings that have led to the delineation of HFimpEF. Additionally, we highlight the importance of understanding LV trajectory and the potential opportunity for new GDMT management for clinicians when treating patients with HFimpEF., Competing Interests: Dr. Wilcox is a consultant for Abbott, Abiomed, Astra Zeneca, and Boehringer Ingelheim. The other authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Backgrounds: A soluble guanylyl cyclase stimulator vericiguat has been shown to reduce cardiovascular mortality or hospitalization for heart failure in patients with worsening heart failure in the VICTORIA study. However, little is known about the effects of vericiguat on biventricular structure and function., Methods and Results: A retrospective analysis of 63 consecutive patients with heart failure with reduced ejection fraction (HFrEF) who were treated with vericiguat was performed. Clinical data and echocardiographic parameters were compared between baseline and follow-up after the initiation of vericiguat. The median follow-up duration was 266 days. Treatment with vericiguat significantly reduced the plasma BNP levels (log-transformed) compared to baseline (2.46 ± 0.51 vs. 2.14 ± 0.58, p < 0.0001). Left ventricular end-diastolic volume index and left ventricular end-systolic volume index were significantly reduced (LVEDVI, 113.5 ± 46.3 vs. 103.6 ± 51.0, p = 0.0056; LVESVI, 82.0 ± 41.9 vs. 72.8 ± 44.7, p = 0.0077; respectively). The tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, an indicator of right ventricle-pulmonary artery (RV-PA) coupling, increased significantly after the treatment (0.56 ± 0.29 vs. 0.92 ± 1.09, p < 0.0001). Univariate and multivariate analyses showed that the treatment effects of vericiguat on BNP levels, LV reverse remodeling, and RV-PA coupling were not correlated with the achievement of the quadruple therapy with beta-blockers, renin-angiotensin system inhibitors, mineralocorticoid inhibitors, and sodium-glucose cotransporter-2 inhibitors, nor with worsening heart failure (WHF)., Conclusion: Treatment with vericiguat improved adverse LV remodeling and RV-PA uncoupling in HFrEF patients. These effects were independent of WHF and achieving the quadruple therapy. Patients with HFrEF may benefit from early initiation of vericiguat to prevent biventricular adverse remodeling., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) is effective for patients with heart failure with QRS duration (QRSd) ≥150 ms. However, its beneficial effect seems to be limited for those with "mid-range" QRSd (120-149 ms). Recent studies have demonstrated that modifying QRSd to left ventricular end-diastolic volume (LVEDV)-modified QRSd-improves the prediction of clinical outcomes of CRT., Objective: The purpose of this study was to investigate the clinical impact of the modified QRSd on the efficacy of CRT in patients with "mid-range" QRSd., Methods: We conducted a retrospective, multicenter, observational study, with heart failure hospitalization (HFH) after CRT as the primary endpoint. Modified QRSd is defined as QRSd divided by LVEDV, determined through the Teichholtz method of echocardiography., Results: Among the 506 consecutive patients considered, 119 (mean age 61 ± 15 years; 80% male, QRSd 135 ± 9 ms) with a "mid-range" QRSd who underwent de novo CRT device implantation were included for analysis. During median follow-up of 878 days [interquartile range 381-1663 days], HFH occurred in 45 patients (37%). Fine-Gray analysis revealed modified QRSd was an independent predictor of HFH (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.96-0.99; P <.01). Receiver operating characteristic curve analysis revealed a cutoff value of 0.65 ms/mL for the modified QRSd in predicting HFH. Patients above the threshold exhibited a significantly lower incidence of HFH than patients below the threshold (HR 0.46; 95% CI 0.25-0.86; P = .01)., Conclusion: Modified QRSd can effectively predict the efficacy of CRT in patients with a "mid-range" QRSd., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100 mmHg in systole) than for the non-low blood pressure group (> 100 mmHg in systole) (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Left ventricular (LV) systolic dysfunction represents a highly treatable cause of heart failure (HF). A substantial proportion of patients with HF with reduced ejection fraction (EF;HFrEF) demonstrate improvement in LV systolic function (termed HF with improved EF [HFimpEF]), either spontaneously or when treated with guideline-directed medical therapy (GDMT). Although it is a relatively new HF classification, HFimpEF has emerged in recent years as an important and distinct clinical entity. Improvement in LVEF leads to decreased rates of mortality and adverse HF-related outcomes compared to patients with sustained LV systolic dysfunction (HFrEF). While numerous clinical and imaging factors have been associated with HFimpEF, identification of which patients do and do not improve requires further investigation. In addition, patients improve at different rates, and what determines the trajectory of HFimpEF patients after improvement is incompletely characterized. A proportion of patients maintain improvement in LV systolic function, while others experience a recrudescence of systolic dysfunction, especially with GDMT discontinuation. In this review we discuss the contemporary guideline-recommended classification definition of HFimpEF, the epidemiology of improvement in LV systolic function, and the clinical course of this unique patient population. We also offer evidence-based recommendations for the clinical management of HFimpEF and provide a roadmap for future directions in understanding and improving outcomes in the care of patients with HFimpEF., Competing Interests: Declaration of competing interest Dr. Pensa reports no disclosures. Dr. Shah is supported in part by grants from the National Institutes of Health and the American Heart Association. In the past 12 months, Dr. Shah has served as a consultant for Amgen and Cytokinetics. Dr. Shah is a co-inventor on a patent for ex-RNAs signatures of cardiac remodeling. Dr. Khan is supported in part by grants from the National Institutes of Health. Dr. Wilcox is supported in part by grants from the National Institutes of Health. Dr. Wilcox serves as a consultant/advisory board for Astra Zeneca, Abiomed, Abbott, Boehringer Ingelheim and Cytokinetics., (Copyright © 2024. Published by Elsevier Inc.)

Late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) prevents left ventricular reverse remodeling (LVRR), resulting in a poor prognosis. However, the prognosis of patients who have LGE and achieve LVRR and patients who do not have LGE and do not achieve LVRR remains unknown. This study aimed to answer this question by sorting patients with heart failure based on the presence of LGE and LVRR and comparing their prognoses. Another aim was to identify useful factors for predicting LVRR.All patients were followed-up for 24 months. LVRR was defined as a ≥ 10% increase at the last follow-up at 12 ± 6 months from baseline, on echocardiography. The primary endpoint was a composite of cardiovascular death and hospitalization due to worsening heart failure within 18 ± 6 months. Baseline data and data from each outpatient visit were collected and analyzed. We enrolled 80 consecutive patients with heart failure and reduced left ventricular ejection fraction (< 50%) who underwent CMR.LGE was positive in 40 patients (50.0%) and LVRR was observed in 50 patients (63%). The incidence of the primary endpoint was significantly lower in the group that achieved LVRR, regardless of LGE status (LGE-positive group, P = 0.01; LGE-negative group, P = 0.02). In the multivariate analysis, the percentage change in NT-pro BNP levels at 3 months, NT-pro BNP levels at 6 months, and age were independent predictors of LVRR.LGE-positive patients may have a better prognosis if they achieve LVRR. Serial NT-pro BNP testing may be a valuable predictor of LVRR.

Objective Spontaneous mechanical alternans (MA), or pulsus alternans, has been observed in heart failure patients with hypertension or tachycardia for 150 years and is considered a sign of a poor prognosis. However, in some dilated cardiomyopathy (DCM) patients with MA, optimal medical therapy (OMT) brings left ventricular reverse remodeling (LVRR), a preferable prognostic indicator. This study examined the probability of LVRR in DCM patients with spontaneous MA and whether or not LVRR can be predicted by the baseline blood pressure or heart rate. Methods We conducted a single-center, retrospective observational study of newly diagnosed DCM patients from January 2017 to December 2020. Results Thirty-three newly diagnosed DCM patients were retrospectively examined. Spontaneous MA was observed during diagnostic cardiac catheterization in at least 1 of the pressure waveforms of the aorta, left ventricle, pulmonary artery, or right ventricle in 10 patients (30%) (MA-group). LVRR after OMT was achieved roughly equally in the MA group (6 of 10, 60%) and the non-MA group (12 of 23, 52%). In the MA group, those who achieved LVRR had a significantly higher baseline systolic aortic pressure (more than 120 mmHg in all 6 patients) than those who did not, although the baseline heart rate did not show a significant correlation with LVRR. In contrast, in the non-MA group, LVRR was unrelated to the baseline aortic pressure or heart rate. Conclusion The probability of LVRR in newly-diagnosed DCM patients with spontaneous MA was similar to that in those without spontaneous MA. Spontaneous MA may not necessarily be a sign of a poor prognosis if observed in patients with a preserved blood pressure.

Background: Myocardial fibrosis may increase vulnerability to poor prognosis in patients with heart failure (HF), even in those patients exhibiting left ventricular reverse remodeling (LVRR) after guideline-based therapies., Objectives: This study sought to characterize fibrosis at baseline in patients with HF with left ventricular ejection fraction (LVEF) <50% by determining serum collagen type I-derived peptides (procollagen type I C-terminal propeptide [PICP] and ratio of collagen type I C-terminal telopeptide to matrix metalloproteinase-1) and to evaluate their association with LVRR and prognosis., Methods: Peptides were determined in 1,034 patients with HF at baseline. One-year echocardiography was available in 665 patients. Associations of peptides with 1-year changes in echocardiographic variables were analyzed by multivariable linear mixed models. LVEF was considered improved if it increased by ≥15% or to ≥50% or if it increased by ≥10% to >40% in patients with LVEF ≤40%. Cardiovascular death and HF-related outcomes were analyzed in all patients randomized to derivation (n = 648) and validation (n = 386) cohorts., Results: Continuous associations with echocardiographic changes were observed only for PICP. Compared with high-PICP (≥108.1 ng/mL) patients, low-PICP (<108.1 ng/mL) patients exhibited enhanced LVRR and a lower risk of HF-related outcomes (P ≤ 0.018), with women and nonischemic patients with HF showing a stronger LVEF increase (interaction P ≤ 0.010). LVEF increase was associated with a better prognosis, particularly in low-PICP patients (interaction P ≤ 0.029). Only patients with both low PICP and improved LVEF exhibited a better clinical evolution than patients with nonimproved LVEF (P < 0.001)., Conclusions: Phenotyping with PICP, a peptide associated with myocardial fibrosis, may be useful to differentiate patients with HF who are more likely to experience clinical myocardial recovery from those with partial myocardial improvement., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the Spanish Ministry of Science, Innovation, and Universities (MICINN) (SAF2017-84324-C2-1-R, SAF2017-85574-R and DPI2017-83721-P); the Institute of Health Carlos III (ISCIII) (PI17/01487, PI18/00256, PIC18/00014, PI18/01469 and PI20/01319), CIBER Cardiovascular (CB16/11/00403 and CB16/11/00483) projects, as a part of the National R&D&I Plan, cofunded by ISCIII-Sub-Directorate-General for Research Assessment and Promotion and the European Regional Development Fund (ERDF); Directorate General of Industry, Energy and Innovation, Government of Navarra (MINERVA II project) and the European Commission (HOMAGE-2012-305507 and H2020-CRUCIAL-2019-848109-2). Dr Bayés-Genís has received grants and personal fees from AstraZeneca, Vifor, Boehringer Ingelheim, Novartis, Roche Diagnostics, and Critical diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association between different right ventricular (RV) lead positions as assessed by cardiac computed tomography (CT) and echocardiographic and clinical outcomes in patients receiving cardiac resynchronization therapy (CRT)., Methods: We reviewed patient records of all 278 patients included in two randomized controlled trials (ImagingCRT and ElectroCRT) for occurrence of heart failure (HF) hospitalization or all-cause death (primary endpoint) during long-term follow-up. Outcomes were compared between RV lead positions using adjusted Cox regression analysis. Six months after CRT implantation, we estimated left ventricular (LV) reverse remodeling by measuring LV end-systolic and end-diastolic volumes by echocardiography. Changes from baseline to 6 months follow-up were compared between RV lead positions. Device-related complications were recorded at 6-month follow-up., Results: During median (interquartile range) follow-up of 4.7 (2.9-7.1) years, the risk of meeting the primary endpoint was similar for patients with non-apical vs. apical RV lead position (adjusted hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.54-1.12, p = 0.17) and free wall vs. septal RV lead position (adjusted HR 1.03, 95% CI 0.72-1.47, p = 0.86). Changes in LV ejection fraction and dimensions were similar with the different RV lead positions. We observed no differences in device-related complications relative to the RV lead position., Conclusions: In patients receiving CRT, the risk of HF hospitalization or all-cause death during long-term follow-up, and LV remodeling and incidence of device-related complications after 6 months are not associated with different anatomical RV lead position as assessed by cardiac CT., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Many patients with dilated cardiomyopathy (DCM) progress to heart failure (HF), although some demonstrate left ventricular (LV) reverse remodeling (LVRR), which is associated with better outcomes. The pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio has been used as a prognostic predictor in patients with HF, although this tool's usefulness in predicting LVRR remains unknown., Methods and results: Data from a prospective observational study of 211 patients diagnosed in 2000-2020 with DCM were retrospectively analyzed. Sixty-nine patients with New York Heart Association class I or II HF were included. LVRR was observed in 23 patients (33.3%). The mean LV ejection fraction (29%) and LV end-diastolic dimension (64.5 mm) were similar in patients with and without LVRR. The PAD/AoD ratio was significantly lower in patients with LVRR than those without (81.4% vs. 92.4%, respectively; P=0.003). The optimal PAD/AoD cut-off value for detecting LVRR was 0.9 according to the receiver operating characteristic curve analysis. Multivariate analysis identified a PAD/AoD ratio ≥0.9 as an independent predictor of presence/absence of LVRR. Cardiac events were significantly more common in patients with a PAD/AoD ratio ≥0.9 than those with a ratio <0.9, after a median follow up of 2.5 years (log-rank, P=0.007)., Conclusions: The PAD/AoD ratio can predict LVRR in patients with DCM.

Background: Right ventricular pacing (RVP) induces abnormal electrical activation and asynchronous ventricular contraction and leads to pacing induced cardiomyopathy (PICM) in 10%-20% of patients. Cardiac resynchronization therapy (CRT) utilizing biventricular pacing (BVP) is the recommended treatment. Left bundle branch pacing (LBBP) is a novel physiological pacing technique which may serve as an alternative to CRT. This study assessed feasibility and outcomes of LBBP delivered CRT in patients with PICM., Methods: Total 20 consecutive patients with PICM who received an upgrade of their pacemaker to LBBP were prospectively studied. Acute success rate, complications, functional and echocardiographic response, and hospitalization for heart failure within 6 months from implantation were evaluated., Results: LBBP was successfully delivered in all patients. Median duration of RVP before upgrade to LBBP was 3.8 years and the RVP was 99%. LBBP resulted in significant QRS narrowing (from 193 ± 18 ms to 130 ± 17 ms [p < .001]), improvement in LVEF (from 32% ± 6 % to 47% ± 8% [p < .001]) and NYHA class (from 2.8 ± 0.4 to 1.4 ± 0.5 [p < .001]) at 6 months. No LBBP-related complications occurred. No patients were hospitalized for heart failure or died., Conclusion: LBBP is feasible and safe in delivering CRT in PICM. Preliminary analyses demonstrated significant electrical resynchronization and favorable improvement in LV function and NYHA functional class at short term follow-up. Data needs to be validated in large randomized controlled trials., (© 2022 Wiley Periodicals LLC.)

Background: Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT)., Objective: The purpose of this study was to evaluate the impact of baseline LV volumes on LV reverse remodeling after CRT and whether this is associated with improved survival., Methods: Patients were stratified into quintiles according to baseline LV end-diastolic volume indexed for body surface area (LVEDVi). LV reverse remodeling was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up after CRT. Independent associates of LV remodeling were assessed and long-term mortality rates were compared between patients with and without LV reverse remodeling (across LVEDVi quintiles)., Results: A total of 864 patients were included (mean age 66 ± 10 years; 657 patients (76%) were male), of whom 101 (12%) were in quintile 1 (<65 mL/m 2 ), 272 (32%) in quintile 2 (65-95 mL/m 2 ), 247 (29%) in quintile 3 (95-125 mL/m 2 ), 151 (18%) in quintile 4 (125-155 mL/m 2 ), and 93 (11%) in quintile 5 (>155 mL/m 2 ). Patients with larger baseline LVEDVi had worse survival after CRT (log-rank, P = .019). The cumulative 10-year survival was significantly better in patients with vs without LV reverse remodeling (48.7% vs 33.9%; P < .001). Significant LV reverse remodeling was observed in all LVEDVi quintiles. In addition, patients with LV reverse remodeling had superior survival than did patients without LV reverse remodeling, regardless of baseline LVEDVi quintile (log-rank, P < .05 for all)., Conclusion: Many patients with larger baseline LV volumes still show significant LV reverse remodeling after CRT and had superior survival (regardless of baseline LV volumes) than did patients without LV reverse remodeling. Therefore, CRT should not be denied on the basis of severe LV dilatation., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) reverse remodeling has been identified as a strong predictor of long-term survival in patients receiving CRT. Interestingly, CRT induces reverse remodeling in the left atrium (LA) as well. It is currently unknown to what extent LA reverse remodeling is correlated to long-term survival after CRT. This study aims to assess the long-term prognostic value of left atrium (LA) reverse remodeling in patients undergoing cardiac resynchronization therapy (CRT)., Methods: Baseline and 3-months follow-up echocardiograms after CRT implantation were prospectively assessed to determine changes in left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), left atrial volume (LAV), and left atrial reservoir strain (LAS r ). Multivariate Cox regression analysis was performed to identify predictors for long-term survival., Results: In our study population of 99 patients with a mean follow-up of 6.3 ± 2.1 years, 43 patients (43%) reached the end-point of all-cause mortality. More extensive LA reverse remodeling, as measured by a relative increase in LAS r , was observed in survivors compared to non-survivors (43 [29-64] % vs. 8 [2-28] %, P < 0.001, respectively). After multivariate analysis, delta LAS r remained the only significant predictor of mortality [HR per 5%: 0.90 (0.86-0.95); AUC 0.78 (0.68-0.88)]., Conclusion: An increase in LAS r is associated with favorable long-term outcome after CRT. The observed clinical importance of LA reverse remodeling after CRT asks for further validation in larger prospective cohorts., (© 2021. Japanese Society of Echocardiography.)

Background: The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled., Objectives: The study sought to assess the prognostic impact of disease-causing genetic variants in DCM., Methods: Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR)., Results: After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.09-2.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction ≤35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene., Conclusions: In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the following institutions: the Instituto de Salud Carlos III (AC16/0014, PI18/0004, PI20/0320) and the European Union (GENPROVIC project from ERA-CVD framework). The Hospital Universitario Puerta de Hierro and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARD-Heart). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The number of heart failure (HF) patients has been rapidly increasing in Japan, and considering the most explosive aging occurring in Asia, the management of elderly HF patients and longer life expectancy are critical issues. The aim of the present study was to evaluate whether the mid-term prognosis after cardiac resynchronization therapy (CRT) implantation was influenced by age and to investigate, in detail, the difference in the change ratio of echocardiographic parameters according to the age group of interest., Methods and Results: This retrospective analysis included 173 patients who underwent CRT implantation in our hospital from February 2008 to March 2019. Eighty patients (46%) were classified into the elderly group (≥75 years) and the rest in the non-elderly group. The study population was also classified with propensity score matching. The mid-term prognosis including all-cause death and hospitalization for HF, and the ratio of CRT responders were compared between the 2 groups. CRT response was defined as left ventricular (LV) end-systolic volume reduction ≥15% at follow-up echocardiography within a year. During a median follow-up of 1057 [interquartile range: 412, 2107] days, adverse events were not significantly different between the 2 groups before and after matching (before matching; all-cause death: log-rank p = 0.323, hospitalization for HF: log-rank p = 0.376, after matching; all-cause death: log-rank p = 0.325, hospitalization for HF: log-rank p = 0.516). Moreover, the rate of CRT responders was not significantly different between the 2 groups before and after matching (before matching, p = 0.718; after matching, p = 0.666)., Conclusions: In elderly HF patients, CRT provided the same clinical benefits as in non-elderly HF patients, furthermore, there was a similar trend in LV reverse remodeling between the 2 groups. The present study demonstrated that the indication of CRT implantation should not be determined by age., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Multipoint pacing [Multipoint™ Pacing (MPP), Abbott] via a single left ventricular lead (Quartet™ LV lead, Abbott) improves acute left ventricular (LV) function and response to cardiac resynchronization therapy (CRT). Aim of this study was to examine additional benefits in terms of LV reverse remodeling and CRT response by activating MPP in responders and non-responders to conventional biventricular pacing (CONV)., Methods: 43 consecutive patients receiving CRT (Quadra Assura MP™, Abbott) received LV dP/dt max optimized CONV programming for 6 months. MPP programming with large anatomical electrode separation (> 30 mm) and basal LV1 pacing location was activated afterwards. Echocardiographic and clinical parameters were obtained at baseline, 6- and 12-month follow-up (FU). The response was defined as an improvement of LVESV ≥ 15% and super-response as improvement ≥ 30% relative to baseline., Results: 41 patients completed FU (one died of non-cardiac cause and one was lost to FU) and after 6 months CONV, 26 patients (63%) were classified as CRT responders. With MPP, the response rate increased to 90% (p < 0.001). Super-response also improved significantly with MPP compared to CONV (71% vs. 22%; p < 0.005). LV reverse remodeling in terms of LVESV improved significantly with MPP compared to CONV (79 ± 45 ml vs. 103 ± 64 ml; p < 0.001). NYHA-class only improved significantly with CONV relative to baseline (1,8 ± 0,7 vs. 2,7 ± 0,5; p < 0.001), but not further with MPP (1,7 ± 0,6 vs. 1,8 ± 0,7; p = 0.49)., Conclusion: Multipoint pacing significantly improves response and super-response to CRT as well as LV reverse remodeling compared to conventional biventricular pacing.

Sacubitril/valsartan has been shown to improve clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF), but its effects on left ventricular (LV) systolic function and reverse remodeling parameters remain to be established. We hereby describe the case of a 41 year old man with HFrEF and severe reduction of left ventricular ejection fraction (LVEF). The patient was first treated with triple HF therapy (beta-blocker, angiotensin converting enzyme inhibitor and mineralocorticoid antagonist), but after three months he was still symptomatic and with an LVEF firmly low. In consideration of poor response to therapy, we switched angiotensin converting enzyme inhibitor to sacubitril/valsartan to the maximum tolerated dose (49/51 mg bid) with a marked improvement in LV systolic function and reduction in LV volumes at follow-up. In light of the almost normalized LVEF the patient was also removed from the list for the implantation of a cardiac resynchronization therapy defibrillator. In conclusion, our case showed a strong beneficial effect of sacubitril/valsartan on reverse remodeling and LVEF beyond the benefits of concomitant optimal medical therapy. This result is particular noteworthy because it was obtained although the patient wasn't able to reach the full dose of the drug. Physicians should always consider this drug effect when more demanding therapeutic strategies are needed for their HF patients.

Background: We aimed to evaluate effect of heart rate (HR) reduction on left ventricular reverse remodeling (LVRR) in Korean patients with heart failure with reduced ejection fraction (HFrEF)., Methods: Ambulatory patients with HFrEF, who had paired echocardiograms, N-terminal prohormone brain natriuretic peptide (NT-proBNP), and global assessment score (GAS) at baseline and 6-month (n = 157), were followed up on preset treatment schedule with bisoprolol., Results: The LVRR occurred in 49 patients (32%) at 6-month. In multivariable analysis, independent predictors associated with LVRR were use of anti-aldosterone agent (odds ratio [OR], 4.18; 95% confidence interval [CI], 1.80-9.71), young age (OR, 0.96; 95% CI, 0.92-0.99), high baseline HR (OR, 3.76; 95% CI, 1.40-10.10), and favorable baseline GAS (OR, 1.73; 95% CI, 1.06-2.81). Beneficial effect of bisoprolol, in terms of LVRR, NT-proBNP, and GAS, was remarkable in the high HR group (baseline HR ≥ 75 beats per minute [bpm]), which showed a large HR reduction., Conclusion: High baseline HR (≥ 75 bpm) showed an association with LVRR and improvement of NT-proBNP and GAS in patients with HFrEF. This seems to be due to a large HR reduction after treatments with bisoprolol. Trial registry at www.ClinicalTrials.gov, NCT00749034., Competing Interests: Disclosure: The authors have no potential conflicts of interest to disclose.

Background: A prophylactic implantable cardioverter defibrillator (ICD) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) is only indicated when left ventricular ejection fraction (LVEF) reassessment remains ≤35% after 3-6 months on optimal pharmacological therapy. However, LVEF may not improve during this period and the patient may be exposed to an unnecessary risk of sudden cardiac death. This study aimed to determine the incidence and predictors of the absence of left ventricular reverse remodeling (LVRR) after pharmacological treatment optimization in patients with HFrEF to design a risk score of absence of LVRR., Methods: Consecutive outpatients with LVEF ≤35% were included in this observational prospective study. Up-titration of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradine was performed in our Heart Failure (HF) Unit. The absence of LVRR was defined as the persistence of an LVEF ≤35% at the 6-month follow-up., Results: One hundred and twenty patients were included. At the 6-month follow-up, 64%, 76%, 72%, and 7% of patients were at 100% of the target dose of ACE inhibitors/ARBs, beta-blockers, MRAs, and ivabradine, respectively. LVRR was observed in 48% of the patients. Ischemic cardiomyopathy, prolonged HF duration, and larger left ventricular end-diastolic diameter index (LVEDDI) were independent predictors of the absence of LVRR. The risk score based on these predictors showed a c-statistic value of 0.81., Conclusions: Pharmacological treatment optimization is associated with LVRR in approximately half of cases, reducing potential ICD indications in parallel. However, ischemic cardiomyopathy, prolonged HF duration, and larger LVEDDI predict the absence of LVRR and favor ICD implantation without delay. The risk score based on the former predictors may help the clinician with the timing of ICD implantation., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The clinical impact of left ventricular (LV) segmental wall motion abnormalities (SWMA) in patients with idiopathic dilated cardiomyopathy (IDCM) has not been well elucidated.Among 100 consecutive IDCM patients with follow-up visits, we enrolled 85 after excluding those with left bundle branch block and/or ventricular pacemaker implantation. LV wall motion was assessed using left ventriculography scored for 7 segments according to the American Heart Association classification as follows: 0, normokinesis; 1, hypokinesis; 2, akinesis; and 3, dyskinesis. SWMA were defined as a score dispersion of more than 1 degree among the segments.SWMA was exhibited by 26 patients. Kaplan-Meier curves demonstrated that the patients with SWMA (SWMA+) had a significantly higher cardiac event-free rate than the patients without SWMA (P < 0.001). Cox proportional hazards analysis showed that SWMA+ was an independent predictor of cardiac events (P = 0.03; hazard ratio = 3.38; 95% confidence interval [CI], 1.11-10.8). Furthermore, multiple regression analysis showed that SWMA+ was an independent predictor of decreased LV end-systolic dimension index after optimal pharmacotherapy (β = -0.24; 95%CI, -9.12 to -0.73; P = 0.02).SWMA is common in patients with IDCM and is independently associated with a poor prognosis and less morphometric and functional improvement of LV in response to pharmacotherapy.

In idiopathic dilated cardiomyopathy (DCM), myocardial deformational parameters and their relationships remain incompletely characterized. We measured those parameters in patients with DCM, during left ventricular reverse remodeling (LVRR). Prospective study of 50 DCM patients (in sinus rhythm), with left ventricular ejection fraction (EF) <40%. LVRR was defined as an increase of ten units of EF and decrease of diastolic left ventricular diameter (LVDD) in the absence of resynchronization therapy. Performed morphological analysis, myocardial performance quantification (LV and RV Tei indexes) and LV averaged peak systolic longitudinal strain (SSR long) and circumferential strain (SSR circ). At baseline, mean EF was 25.4 ± 9.8%, LVDD was 62.4 ± 7.4 mm, LVDD/BSA of 34.2 ± 4.5 mm/m 2 and 34% had MR grade >II/IV. LVRR occurred in 34% of patients within 17.6 ± 15.6 months and was associated with a reduced rate of death or heart failure hospitalization (5.9% vs. 33.3; p = 0.03). Patients with LVRR had a final EF of 48.9 ± 7.9% (Δ LV EF of 22.4%) and there was a significant decrease (p < 0.05) in: LVDD/BSA, LV systolic diameter/BSA, LV diastolic volume, LV systolic volume, LV mass; an increase (p < 0.05) in sphericity index. However, measures of diastolic function (LA volume/BSA, e'velocity and' E/e'ratio), final LV and RV Tei indexes were not significantly different from baseline. Additionally, final SSR circ and SSR long values were not different from basal. Patients who recovered EF >50% (n = 10), SSR circ and SSR long were inferior to normal. Improvement in EF occurred in one-third of DCM pts and was associated with a decrease of major cardiac events. There was an improvement of diastolic and systolic volumes and in sphericity index, confirming truly LV reverse reshaping. However, myocardial performance indexes, SSR long and SSR circ in reverse-remodeled DCM were still abnormal, suggesting a maintained myocardial systolic and diastolic dysfunction.

Background: The left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (DCM) and the treatment with carvedilol in infants with severe heart failure remain poorly understood., Methods: We reviewed the medical records of 5 infants around 12 months old referred to our hospital with severe heart failure due to DCM. Increased left ventricular fractional shortening (LVFS) by more than 10% and the percent of normal of left ventricular end-diastolic dimension (%LVDd) less than 120% were defined as LVRR in this study., Results: DCM onset ranged from 8 to 16 months. Initial treatment of their acute heart failure was successful in all 5 but 4 patients relapsed despite the usual dose of carvedilol (induction 0.02-maintenance 0.4mg/kg/day), and developed worsening heart failure. Brain natriuretic peptide (BNP) levels which increased again after the acute treatment had fallen subsequent to discontinuing or decreasing carvedilol. Over 24 months, LVFS had increased from 11±2% (mean±SD) to 34±5% (p<0.05), and %LVDd decreased from 149±27% to 108±11% (p<0.05)., Conclusions: LVRR was found at 2 years after the onset of DCM. Usual dose induction of carvedilol therapy can sometimes worsen heart failure after successful initial conventional treatment for the acute heart failure in DCM. Close control of carvedilol treatment may determine the prognosis of infantile DCM around 12 months old. It is prudent to increase low-dose carvedilol slowly corresponding with the BNP level., (Copyright © 2015. Published by Elsevier Ltd.)

Background: The relationship between changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic or clinical definitions of response to cardiac resynchronization therapy (CRT) has not been evaluated. The aims of the present evaluation were to assess: (1) the relationship between changes in NT-proBNP after 6 months of CRT and clinical and echocardiographic responses; (2) the association between NT-proBNP changes and long-term outcome., Methods: In 170 patients treated with CRT (age 61 ± 11 years, 75% male), clinical and echocardiographic parameters and circulating NT-proBNP levels were assessed at baseline and 6 months after CRT. At 6 months follow-up, improvement in New York Heart Association class ≥ 1 point, decrease in left ventricular end-systolic volume ≥ 15%, and decrease in NT-proBNP ≥ 15% defined clinical, echocardiographic, and neurohormonal CRT response, respectively. All-cause mortality data were collected and related to neurohormonal response., Results: Neurohormonal, echocardiographic, and clinical response rates were 54%, 58%, and 66%, respectively. The majority of patients (71%) showing echocardiographic response had NT-proBNP reduction ≥ 15%. In contrast, only 58% of patients who showed clinical response also had NT-proBNP reduction ≥ 15%. During a median follow-up of 32 months, 40 patients died. Patients with neurohormonal response demonstrated a superior long-term outcome compared to patients without neurohormonal response (log-rank P = 0.02)., Conclusions: NT-proBNP reduction ≥ 15% showed better agreement with echocardiographic response compared to clinical response. Neurohormonal response was associated with superior long-term outcome compared to insufficient reduction in NT-proBNP levels., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: Prediction of response to cardiac resynchronization therapy (CRT) is still an unsolved major issue. The interface between left ventricular mechanics, coronary sinus (CS) lead, and pacing delivery has been little investigated., Objective: To investigate CS lead tip movements at baseline and during biventricular pacing (BiV) in the hypothesis that they could provide some insights into left ventricular mechanical behavior in CRT., Methods: Three-dimensional reconstruction of CS lead tip trajectory throughout the cardiac cycle using a novel fluoroscopy-based method was performed in 22 patients with chronic heart failure (19 men; mean age 70 ± 10 years). Three trajectories were computed: before (T-1) and immediately after (T0) BiV start-up and after 6 months (T1). CRT response was the echocardiographic end-systolic volume reduction ≥15% at T1. Metrics describing trajectory at T0, T-1, and T1 were compared between 9 responders (R) and 13 nonresponders (NR)., Results: At T-1 trajectories demonstrated heterogeneous shapes and metrics, but at T0 the variations in the ratio between the two main axes (S1/S2) and in the eccentricity were statistically different between R and NR, pointing out a trajectory's change toward a significantly more circular shape at BiV start-up in R. Remarkably, R and NR could be completely separated by means of the percent variation in S1/S2 from T-1 to T0 (R: 47.5% [31.5% to 54.1%] vs. NR: -25.6% [-67% to -6.5%]). This single marker computed at T0 would have predicted CRT response at T1., Conclusions: Preliminary data showed that CS lead tip trajectory changes induced by BiV were related to mechanical resynchronization., (© 2013 Heart Rhythm Society. All rights reserved.)

Jia Shi,1,2,&ast; Meng-Jiao Shao,3,&ast; Miao Yu,1,2 Bao-Peng Tang1,2 1Cardiac Pacing and Physiological Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bao-Peng Tang, Cardiac Pacing and Physiological Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Email tangbaopeng1111@163.comBackground: Inflammation and cardiac fibrosis are important pathogenic drivers of heart failure. The fibrosis-4 index (FIB-4) is associated with a higher degree of fibrosis. The systemic immune inflammation index (SII) is associated with a higher degree of systemic inflammation status. Previous studies have shown that they are associated with a poor prognosis for cardiovascular disease. We sought to investigate the value of FIB-4 combined with the SII as a novel inflammation-fibrosis combined index (IFCI) in predicting left ventricular reverse remodeling (LVRR) and prognosis among reduced ejection fraction heart failure (HFrEF) patients.Methods: A total of 895 patients with HFrEF were continuously recruited. Receiver operating characteristic curves were drawn to assess the abilities of inflammation-fibrosis indicators to predict LVRR. Multivariable Cox regression analysis was used to examine independent predictors of composite cardiac events and all-cause death.Results: After six months of follow-up, 344 (38.4%) patients experienced LVRR. The IFCI had the largest area under the curve (0.835, P < 0.001). In multivariate-adjusted logistic regression analyses, FIB-4, SII, and IFCI were predictive of LVRR (P value < 0.05). The IFCI was associated with a 3.686-fold higher risk of non-LVRR (odds ratio [OR] = 3.686, P < 0.001). Moreover, an increased IFCI predicted a poor prognosis in HFrEF patients. The highest risk of composite cardiac events (hazard ratio [HR] = 2.716, P < 0.001) was observed in the top IFCI-tertile group, and similar results were found regarding independent risk indicators of all-cause death.Conclusion: In summary, this study indicated that increased IFCI at admission offers good predictability regarding non-LVRR and predicts the risk of all-cause mortality or composite cardiovascular events due to HFrEF patients and could be used as a novel marker.Keywords: heart failure, left ventricular reverse remodeling, inflammation-fibrosis combined index, fibrosis-4 index, systemic immune inflammation index, prognosis

Aim: Response to cardiac resynchronization therapy varies significantly among patients, with one third of them failing to demonstrate left ventricular reverse remodeling after cardiac resynchronization therapy. Left atrial size and function is increasingly recognized as a marker of disease severity in the heart failure population. The aim of this study was to evaluate whether echocardiographic left atrial indices predict left ventricular reverse remodeling after cardiac resynchronization therapy. Materials and methods: Ninety-nine cardiac resynchronization therapy candidates were prospectively included in the study and underwent echocardiography before and 3-months after cardiac resynchronization therapy implantation. Cardiac resynchronization therapy response was defined as a 15% relative reduction in left ventricular end-systolic volume. Indexed left atrial volume, left atrial reservoir strain, left ventricular end-diastolic volume, and left ventricular ejection fraction along with other known predictors of cardiac resynchronization therapy response (gender, etiology of heart failure, presence of typical left bundle branch block pattern, QRS duration >150 ms) were included in a multivariate logistic regression model to identify predictors for cardiac resynchronization therapy response. Results: Cardiac resynchronization therapy response occurred in n = 63 (64%) patients. The presence of a typical left bundle branch block (OR 4.2, 95 CI: 1.4-12.1, p = 0.009), QRS duration >150 ms (OR 4.2, 95 CI: 1.4-11.0, p = 0.029), and left atrial volume index (OR: 0.6, 95 CI: 0.4-0.9, p = 0.012) remained the only significant predictors for cardiac resynchronization therapy response after three months. None of the baseline left ventricular parameters showed an independent predictive value. Conclusion: Left atrial size at baseline is an independent predictor and is inversely proportional to left ventricular volumetric reverse remodeling in cardiac resynchronization therapy candidates. [ABSTRACT FROM AUTHOR]

ObjectiveAt present, there is no early prediction model of left ventricular reverse remodeling (LVRR) for people who are in cardiac arrest with an ejection fraction (EF) of ≤35% at first diagnosis; thus, the purpose of this article is to provide a supplement to existing research.Materials and methodsA total of 109 patients suffering from heart attack with an EF of ≤35% at first diagnosis were involved in this single-center research study. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, with analysis features including demographic characteristics, diseases, biochemical data, echocardiography, and drug therapy. Extreme gradient boosting (XGBoost), random forest, and logistic regression algorithm models were used to distinguish between LVRR and non-LVRR cases and to obtain the most important features.ResultsThere were 47 cases (42%) of LVRR in patients suffering from heart failure with an EF of ≤35% at first diagnosis after optimal drug therapy. General statistical analysis and machine learning methods were combined to exclude a number of significant feature groups. The median duration of disease in the LVRR group was significantly lower than that in the non-LVRR group (7 vs. 48 months); the mean values of creatine kinase (CK) and MB isoenzyme of creatine kinase (CK-MB) in the LVRR group were lower than those in the non-LVRR group (80.11 vs. 94.23 U/L; 2.61 vs. 2.99 ng/ml; 27.19 vs. 28.54 mm). Moreover, AUC values for our feature combinations ranged from 97 to 94% and to 87% when using the XGBoost, random forest, and logistic regression techniques, respectively. The ablation test revealed that beats per minute (BPM) and disease duration had a greater impact on the model’s ability to accurately forecast outcomes.ConclusionShorter disease duration, slightly lower CK and CK-MB levels, slightly smaller right and left ventricular and left atrial dimensions, and lower mean heart rates were found to be most strongly predictive of LVRR development (BPM).

• Left ventricular reverse remodeling (LVRR) after atrial fibrillation (AF) ablation is common in patients with left ventricular systolic dysfunction. • LVRR was predicted by non-paroxysmal AF without apparent structural heart disease. • Recurrence as persistent AF was associated with LVRR but paroxysmal AF was not. • Patients with LVRR experienced less heart failure hospitalizations and cardiovascular deaths. Left ventricular (LV) reverse remodeling (LVRR) after catheter ablation of atrial fibrillation (AFCA) has not been fully described. This study investigated the predictors and clinical outcomes of LVRR after AFCA in patients with LV systolic dysfunction. Of 3319 consecutive patients who underwent first-time AFCA between January 2012 and October 2019, 376 with a baseline LV ejection fraction of <50% were retrospectively evaluated. They were subjected to 256-slice multidetector computed tomography (MDCT) scanning at baseline and 3 months after AFCA. The LVRR was defined as a decrease in the LV end-systolic volume of ≥15%. The prevalence of LVRR was 83% (n = 306). Multivariate logistic regression analysis including age, body mass index, diabetic status, beta-blocker use, and LV diastolic diameter revealed that the predictors of LVRR were non-paroxysmal atrial fibrillation (AF) (odds ratio, 2.68; 95% confidence interval, 1.42–5.05; p = 0.002) and absence of apparent underlying structural heart disease (4.81; 2.31–10.0; p <0.001). The prevalence of LVRR differed depending on AF recurrence pattern prior to the post-MDCT [no episode vs. paroxysmal episode (lasting <7 days) vs. persistent episode (lasting ≥7 days), 84% vs. 81% vs. 63%, respectively, p = 0.023]. During a median follow-up of 32 months, the incidence of paroxysmal form of AF recurrence was similar, whereas persistent form of AF recurrence was less frequent in patients with LVRR (10.5% vs. 18.6%, p = 0.018). Heart failure hospitalizations (2.3% vs. 15.7%, p <0.001), cardiovascular deaths (0.7% vs. 4.3%, p = 0.015), and all-cause deaths (1.3% vs. 5.7%, p = 0.018) were similarly less frequent in those with LVRR. LVRR after AFCA, which was predicted by non-paroxysmal AF without any apparent structural heart disease at baseline, was associated with persistent form of AF recurrence prior to the evaluation. LVRR was associated with favorable clinical outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Left ventricular (LV) pacing at sites of prolonged LV delay (QLV) or at long interventricular delay (right ventricle [RV]-LV) is strongly associated with cardiac resynchronization therapy (CRT) response. QLV and RV-LV have been independently evaluated, but little is known regarding the interrelationship between these measures or of delay to the RV.Objective: The purpose of this study was to evaluate the relationship between measures of electrical delay on CRT response in the SMART-AV (SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy) trial.Methods: In 419 patients, QLV and RV-LV were measured. CRT response was defined as a >15% reduction in LV end-systolic volume from implant to 6 months. The correlation between QLV and RV-LV and the clinical variables associated with the difference between QLV and RV-LV (QRV) were determined. Multivariable logistic regression was used to analyze the association between these measures on CRT response. A machine learning algorithm was used to construct a classification tree to predict response to CRT.Results: The cohort was 66% male (age 66 ± 11 years), 75% had left bundle branch block; and QRS was 150 ± 25 ms. QLV and RV-LV were highly correlated (R2 = 0.71). A longer QRV was observed among patients with right bundle branch block, ischemic cardiomyopathy, and increased QRS. In a multivariable model including QLV, RV-LV, and other known predictors of CRT response, RV-LV, but not QLV, remained associated with CRT response (odds ratio 1.13; 95% confidence interval 1.02-1.26; P = .017). Combining the 2 measures achieved better prediction of CRT response in the group with intermediate RV-LV.Conclusion: RV-LV is a better predictor of CRT response than QLV. There is incremental value in using both measurements or QRV in certain subpopulations. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Although an increased heart rate (HR) is a strong predictor of poor prognosis in cases of chronic heart failure (HF), the clinical value of HR as a predictor in acute decompensated HF (ADHF) is unclear. Seventy-eight patients with nonischemic dilated cardiomyopathy (NIDCM) with sinus rhythm who were first hospitalized for ADHF from 2002 to 2010 were retrospectively investigated after exclusion of patients with tachycardia-induced cardiomyopathy. The patients were divided into two groups stratified by HR on admission with a median value of 113 beats/min (Group H with HR ≥ 113 beats/min; Group L with HR < 113 beats/min). Despite similar backgrounds, including pharmacotherapy for HF, HR changes responding to titration of β-blocker (BB) therapy and myocardial interstitial fibrosis, left ventricular (LV) ejection fractions improved more significantly 1 year later in Group H than in Group L (57 % ± 11 % vs. 46 % ± 12 %, P < 0.001). Cardiac event-free survival rates were also significantly improved in Group H ( P = 0.038). Multiple regression analysis revealed that only the peak HR on admission was an independent predictor of LV reverse remodeling (LVRR) 1 year later ( β = 0.396, P = 0.005). High HR on first admission for ADHF is a strong predictor of LVRR, with a better prognosis in the event of NIDCM in response to optimal pharmacotherapy, independent of pre-existing myocardial damage and subsequent HR reduction by BB therapy. [ABSTRACT FROM AUTHOR]

Background: The role of atrioventricular optimization (AVO) for cardiac resynchronization therapy (CRT) is controversial. Identifying subgroups that benefit from optimization is important to improve CRT outcomes. Pacing at sites of late electrical activation, as assessed by the QLV interval, improves remodeling with CRT. Objective: To evaluate whether pacing at sites of long left ventricular (LV) electrical delay increases the effectiveness of AVO. Methods: This substudy of the SMART-AV trial included 280 subjects who were randomized to either an electrogram-based AVO (SmartDelay) or nominal atrioventricular delay (120 ms). The QLV interval was defined as the time from the onset of QRS to the LV electrogram peak. CRT response was defined prospectively as a >15% reduction in left ventricular end systolic volume from implant to 6 months. Results: The cohort was 68% men, with a mean age of 66 ± 11 years and LV ejection fraction of 28% ± 8%. Longer QLV durations were significantly associated with CRT response (P < .01) for the entire cohort. Moreover, the benefit of AVO increased as QLV prolonged. At the longest QLV quartile, there was more than a 6-fold increase in the likelihood of a remodeling response compared with nominal atrioventricular delays. Conclusions: Baseline electrical dyssynchrony, as measured by the QLV interval, predicted CRT response. At long QLV intervals, AVO can increase the likelihood of structural response to CRT. AVO and QLV optimized that LV lead location may work synergistically to maximize CRT response. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine the prevalence and prognostic role of left ventricular reverse remodeling (LVRR) in idiopathic dilated cardiomyopathy (IDCM). Background: Tailored medical therapy can lead to LVRR in IDCM. The prevalence and prognostic impact of LVRR remain unclear. Methods: We consecutively enrolled 361 IDCM patients. LVRR was defined as a left ventricular ejection fraction increase of ≥10 U or a left ventricular ejection fraction of ≥50% and a decrease in indexed left ventricular end-diastolic diameter of ≥10% or indexed left ventricular end-diastolic diameter of ≥33 mm/m2 at 24 months (range 9 to 36 months). Follow-up echocardiographic data were available for 242 patients (67%), 34 (9%) died/underwent heart transplantation (HTx) before re-evaluation, and 85 (24%) did not have a complete re-evaluation. After re-evaluation, the surviving patients were followed for 110 ± 53 months; there were 55 deaths (23%) and 32 HTx (13%). Results: LVRR was found in 89 of 242 patients (37%). Baseline predictors of LVRR were higher systolic blood pressure (p = 0.047) and the absence of left bundle branch block (p = 0.009). When added to a prognostic baseline model including male sex, heart failure duration, New York Heart Association functional classes III to IV, LVEF, significant mitral regurgitation, and beta-blockers, LVRR, New York Heart Association functional classes III to IV, and significant mitral regurgitation after 24 months emerged as independent predictors of death/HTx and heart failure death/HTx. The model including follow-up variables showed additional prognostic power with respect to baseline model (for death/HTx, area under the curve: 0.80 vs. 0.70, respectively, p = 0.004). Furthermore, only LVRR was significantly associated with sudden death/major ventricular arrhythmia in the long-term. Conclusions: LVRR characterized approximately one-third of IDCM patients surviving 2 years while receiving optimal medical therapy and allowed a more accurate long-term prognostic stratification of the disease. [Copyright &y& Elsevier]

Cardiac resynchronization therapy improves mortality and heart failure symptoms in patients with sinus rhythm, depressed left ventricular ejection fraction, a wide QRS complex and moderate-to-severe heart failure symptoms. The results of recent trials suggest that in similar patients with minimal heart failure symptoms cardiac resynchronization therapy is associated with left ventricular reverse remodeling, and may prevent the progression of heart failure. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Objectives: This study explored the effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) twist, particularly in relation to LV lead position. Background: LV twist is emerging as a comprehensive index of LV function. Methods: Eighty heart failure patients were included. Two-dimensional echocardiography was performed at baseline, immediately after CRT, and at 6-month follow-up. Speckle-tracking analysis was applied to assess LV twist. The LV lead was placed preferably in a (postero)lateral vein, and at fluoroscopy, the position was classified as basal, midventricular, or apical. Response to CRT was defined as reduction of LV end-systolic volume ≥15% at 6-month follow-up. A control group comprised 30 normal subjects. Results: Peak LV twist in heart failure patients was 4.8 ± 2.6° compared with 15.0 ± 3.6° in the control subjects (p < 0.001). At 6-month follow-up, peak LV twist significantly improved only in responders (56%), from 4.3 ± 2.4° to 8.5 ± 3.2° (p < 0.001). The strongest predictor of response to CRT was the improvement of peak LV twist immediately after CRT (odds ratio: 1.899, 95% confidence interval: 1.334 to 2.703, p < 0.001). Furthermore, LV twist significantly improved in patients with an apical (from 4.3 ± 3.1° to 8.6 ± 3.0°, p = 0.001) and midventricular (from 4.8 ± 2.2° to 6.4 ± 3.9°, p = 0.038) but not with a basal (5.0 ± 3.3° vs. 4.1 ± 3.2°, p = 0.28) LV lead position. Similarly, LV ejection fraction significantly increased in patients with an apical (from 26 ± 7% to 37 ± 7%, p < 0.001) and midventricular (from 26 ± 6% to 33 ± 8%, p < 0.001) but not with a basal (26 ± 5% vs. 28 ± 8%, p = 0.30) LV lead position. Conclusions: An immediate improvement of LV twist after CRT predicts LV reverse remodeling at 6-month follow-up. [Copyright &y& Elsevier]