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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/m2, (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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

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

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. 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. 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. 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). Modified QRSd can effectively predict the efficacy of CRT in patients with a "mid-range" QRSd. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective To explore the difference in left ventricular reverse remodeling (LVRR) between coarctation of aorta (CoA) complicated by bicuspid aortic valve (BAV) and that by tricuspid aortic valve (TAV) after percutaneous intervention. Methods The clinical data on 47 patients undergoing percutaneous balloon dilation and stent implantation due to CoA in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2014 to December 2021 were retrospectively analyzed. According to the preoperative imaging data, there were 18 patients with BAVA and 29 with TAV. The results of echocardiography before and one year after the procedure were compared. Results CoA Vmax, CoA PG, LVEDd, LVEDdi, LVM and LVMI were significantly improved in CoA patients one year after percutaneous intervention, and 23.4% of the patients developed left ventricular reverse remodeling. AV Vmax, AV PG and LVEDdi in the patients with BAV were higher than those in the TAV group (P = 0.005 and P = 0.007; P = 0.03), and the rate of left ventricular reverse remodeling in BAV patients was lower than that in TAV patients, but there was no statistical significance. Multivariate analysis did not find any influence factors affecting left ventricular reverse remodeling one year after the procedure. Conclusions Part of the CoA patients develops left ventricular remodeling reversal one year after percutaneous intervention. LVRR in patients with BAV is lower than that in those with TAV, which still needs further clinical research. [ABSTRACT FROM AUTHOR]

Abstract Background For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. Methods We retrospectively reviewed 65 patients with advanced NIDCM (LVEF

Background: For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. Methods: We retrospectively reviewed 65 patients with advanced NIDCM (LVEF < 40%) who underwent mitral surgery. Of them, 47 (72%) underwent mitral annuloplasty and 18 (28%) replacement for secondary MR. The primary endpoint was postoperative reduction in indexed LV end-systolic volume (LVESVI). Results: At baseline, there was no intergroup difference in LVESVI (123 ± 47 vs. 147 ± 37 ml/m2, P = 0.055), LVEF (27 ± 8% vs. 25 ± 6%, P = 0.41), incidence of severe MR (57% (27/47) vs. 72% (13/18), P = 0.40), or EuroSCORE II score (6.2% vs. 7.6%, P = 0.90). At 6 months, the annuloplasty group reduced LVESVI to a greater degree than the replacement group (P < 0.001), yielding significantly smaller postoperative LVESVI (96 ± 59 vs. 154 ± 61 ml/m2, P < 0.001) and better LVEF (P < 0.001). The rates of moderate/severe recurrent MR were 17% (8/47) and 0%, respectively. Multivariable analysis demonstrated that mitral annuloplasty (OR 6.10, 95% CI 1.14–32.8, P = 0.035) was significantly associated with postoperative LV reverse remodeling. Cumulative survival was not different between the groups (P = 0.26). Conclusions: In patients with NIDCM, mitral annuloplasty reduced LV volume to a greater degree than did mitral replacement. These findings may assist with surgical options for secondary MR associated with NIDCM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background In some patients with nonischemic cardiomyopathy (NICM), left ventricular (LV) function improves with medical assistance, resulting in left ventricular reverse remodeling (LVRR). However, predictors of LVRR are not fully understood. The left atrium (LA) has been reported as a prognostic predictor in patients with heart failure (HF). The present study aimed to evaluate clinical predictors of LVRR related to LA function on cardiac magnetic resonance (CMR). Methods A total of 103 patients with reduced left ventricular ejection fraction (LVEF) were enrolled in this retrospective study between September 2015 and July 2021. CMR parameters, including strain data, were measured in all patients. Echocardiographic data obtained approximately 2 years after enrollment were analyzed to assess LVRR. Results LVRR occurred in 46 patients (44.7%) during follow-up. The value of LA conduit strain was higher in the LVRR group than in the non-LVRR group (6.6 [interquartile range (IQR): 5.6–9.3]% versus 5.0 [IQR: 3.0-6.2]%; p 6.2% compared to those with ⩽6.2%. (log-rank test, p = 0.019). Conclusions LA conduit strain derived from CMR is an independent predictor of LVRR in patients with NICM.

BACKGROUND: Left Ventricular reverse remodeling is a major indicator of functional improvement in patients with ischemic cardiomyopathy undergoing revascularization. We aimed to investigate the ability of right ventricular functions to predict left ventricular reverse remodeling (LVRR) in those patients. METHODS Subjects presented with ICM (n=52) were included and underwent right ventricular (RV) functions assessment. By the end of study patients were divided into two groups depending on positive LVRR response defined as =15% decrease in LV endsystolic volume (LVESV). Group 1 (n=28) with positive LVRR and group 2 (n= 24) without. RESULTS A significant difference between the two groups regarding right ventricular systolic tricuspid annular velocity (RV S'), RV myocardial performance index (RV MPI), RV free wall strain (RVFWS) and RV global longitudinal strain (RV GLS) was noticed. RV GLS was superior to RVFWS in prediction of LVRR (AUC difference of 0. 12, P= <0.001) and the later was superior to RV S' and RV MPI in the same regards. CONCLUSION: We conclude that right ventricular function may predict LVRR outcome of revascularization, with the RV GLS being the most powerful predictor. [ABSTRACT FROM AUTHOR]

Background: In some patients with nonischemic cardiomyopathy (NICM), left ventricular (LV) function improves with medical assistance, resulting in left ventricular reverse remodeling (LVRR). However, predictors of LVRR are not fully understood. The left atrium (LA) has been reported as a prognostic predictor in patients with heart failure (HF). The present study aimed to evaluate clinical predictors of LVRR related to LA function on cardiac magnetic resonance (CMR). Methods: A total of 103 patients with reduced left ventricular ejection fraction (LVEF) were enrolled in this retrospective study between September 2015 and July 2021. CMR parameters, including strain data, were measured in all patients. Echocardiographic data obtained approximately 2 years after enrollment were analyzed to assess LVRR. Results: LVRR occurred in 46 patients (44.7%) during follow-up. The value of LA conduit strain was higher in the LVRR group than in the non-LVRR group (6.6 [interquartile range (IQR): 5.6–9.3]% versus 5.0 [IQR: 3.0-6.2]%; p < 0.001). The multivariate logistic regression analysis showed that LA conduit strain was an independent predictor of LVRR (odds ratio [OR]: 1.216, 95% confidence interval [CI]: 1.050–1.408; p = 0.009). The area under the receiver operating characteristic (ROC) curve of the LA conduit strain was 0.746, and the cutoff value was 6.2%. The Kaplan‒Meier analysis revealed that the incidence of adverse cardiac events was significantly lower in patients with LA conduit strain > 6.2% compared to those with ⩽6.2%. (log-rank test, p = 0.019). Conclusions: LA conduit strain derived from CMR is an independent predictor of LVRR in patients with NICM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Mixed aortic valve disease (MAVD) is a frequent concomitant valve disease with unique cardiac pathological changes compared to predominant aortic stenosis (PAS). The previous studies about the MAVD are contradictory. Therefore, a new perspective is needed to assess the value of TAVR for this cohort of patients. Methods: From January 2018 to December 2021, 90 MAVD patients and 72 PAS patients who underwent TAVR in our hospital were collected. 1:1 propensity score matching analysis was used to control the bias in patient selection. The dynamic changes in left ventricular morphology and hemodynamics were compared by generalized estimating equations. Univariate or multivariate logistic regression analysis was used to screen for independent risk factors for the non‐occurrence of left ventricular reverse remodeling (non‐LVRR). Results: After the matching procedure, 112 patients were included in the analysis (56 in each group). Baseline characteristics were similar between the two groups. LVRR occurred in both groups, but MAVD had greater left ventricular end‐diastolic volume index and left ventricular mass index, a higher incidence of mitral regurgitation (MR), and a more pronounced transformation of ventricular geometry patterns. Post‐operative MR (odd ratio [OR]: 10.05; 95% confidence interval [CI]: 2.08–48.57; p <.001) and coronary artery disease (OR: 2.82; 95% CI: 1.08–7.34; p =.034) were independent risk factors for non‐LVRR. Conclusion: LVRR also occurs in patients with MAVD, post‐operative MR and coronary artery disease were independent risk factors for non‐LVRR. [ABSTRACT FROM AUTHOR]

Abstract Background We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT). Methods We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%. Results A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69–78 years) and 56.6% being male. LVMi decreased (P mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and mild at baseline was the only statistically significant predictor of a decrease of LVMi

Background: Delayed heart-to-mediastinum ratio (HMR) has been associated with catecholamine levels and contractile reserve in dilated cardiomyopathy (DCM); however, there is scant evidence regarding the association between cardiac sympathetic activity and left ventricular reverse remodeling (LV-RR). We calculated the 123I-metaiodobenzylguanidine (123I-mIBG) HMR and washout rate (WR) in patients with DCM and investigated their associations with LV-RR. Methods: From April 2003 to January 2020, in 120 patients with DCM who underwent 123I-mIBG scintigraphy. 66 patients undergoing follow-up echo and taking a beta-blocker from baseline were examined the relationship between 123I-mIBG and LV-RR. After that, this prognostic value for composite cardiac events was evaluated in the entire 120 patients. Results: In LV-RR analysis, patients were 50.4 ± 12.2 years, with a mean left ventricular ejection fraction of 28.6%. Of 66 patients, 28 (42.4%) achieved LV-RR. Multiple logistic regression analysis of LV-RR revealed that not delayed HMR but the WR (cutoff value: 13.5%) was an independent predictor of LV-RR (odds ratio 6.514, p = 0.002). In the analysis for composite cardiac events, even though WR itself does not have the prognostic capacity, Kaplan–Meier survival curves divided by the cutoff value (delayed HMR = 2.0, WR = 13.5) showed that delayed HMR and WR values enabled the stratification of high-risk patients (log-rank p < 0.001). Conclusions: The 123I-mIBG WR was associated with the prevalence of LV-RR in patients taking 100% of beta-blockers and 98.5% of renin-angiotensin system inhibitors. Reflecting the contractile reserve, the combined assessment of the delayed HMR and WR could be used to further precisely stratify the patients with DCM. [ABSTRACT FROM AUTHOR]

Background: We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT). Methods: We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%. Results: A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69–78 years) and 56.6% being male. LVMi decreased (P < 0.0001) while EAT volume increased and the average CT attenuation decreased (both P < 0.0001) at one year. Baseline atrial fibrillation (P = 0.042), mitral regurgitation ≥ mild (P = 0.006), aortic regurgitation (AR) > mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and < 15%. AR > mild at baseline was the only statistically significant predictor of a decrease of LVMi < 15% at one year (OR 0.33, 95% CI: 0.13 to 0.84, P = 0.021) in multivariate regression. Conclusions: Concomitant more-than-mild AR might predict better left ventricular reverse remodeling regression after TAVR. [ABSTRACT FROM AUTHOR]

Abstract Background Aortic valve neocuspidization (AVNeo) has emerged as a promising aortic valve procedure, and is expected to have a larger effective orifice area (EOA) than commercially available bioprostheses. It is, however, unclear which indices could facilitate left ventricular (LV) reverse remodeling after AVNeo. The aim of this study is to verify the impact of global left ventricular afterload on the LV reverse remodeling following AVNeo. Methods Data-available consecutive 38 patients (median age, 77; interquartile range, 72.8–82.0) undergoing AVNeo for severe aortic stenosis were enrolled in this study. Preoperative and the last follow-up echocardiographic data were retrospectively analyzed including the valvuloarterial impedance (Zva), a marker of global LV afterload. Reduction in LV geometry index (LVGI) and relative wall thickness (RWT) were used as an indicator for LV reverse remodeling. Results The Zva reduced in 24 patients (63.2%) during the follow-up period (median, 12 months). Reduction in Zva significantly correlated to improvement of LV geometry (LVGI (r = 0.400, p = 0.013) and RWT (r = 0.627, p

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]

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. [ABSTRACT FROM AUTHOR]

Women with severe aortic stenosis (AS) have better long-term prognosis after transcatheter aortic valve implantation (TAVI) compared to men. Whether this is caused by sex-related differences in left ventricular (LV) reverse remodeling after TAVI is unknown. Patients with severe AS who underwent transfemoral TAVI between 2007 and 2018 were selected. LV dimensions, volumes, and ejection fraction (LVEF) were assessed by transthoracic echocardiography before TAVI and at 6 and 12 months follow-up after TAVI. LV reverse remodeling was defined as the percentual LV mass index (LVMi) reduction compared to baseline. The primary outcome was all-cause mortality. A total of 459 patients (80 ± 8 years; 52% male) were included. At 6 and 12 months follow-up, both sexes showed significant reductions in LV volumes and LVMi accompanied by improvement in LVEF, without significant differences between the sexes over time. During a median follow-up of 2.8 [IQR 1.9–4.3] years, 181 (39%) patients died. Women showed better outcomes compared to men (log-rank p = 0.024). In addition, male sex was independently associated with all-cause mortality in multivariable Cox regression (HR 1.423, 95% CI 1.039–1.951, p = 0.028). No association was observed between the interaction of percentual LVMi reduction and sex with outcomes (p = 0.64). Men and women with severe AS had similar improvement in LVEF, and similar reductions in LV volumes and LVMi at 6 and 12 months after TAVI. Women showed better survival after TAVI as compared to men. The superior outcomes noted in women after TAVI are not associated with sex differences in LV reverse remodeling. [ABSTRACT FROM AUTHOR]

Background: A novel cardioprotective drug, vericiguat, reduces the risk of cardiovascular mortality for patients already on guideline-directed medical therapy. However, the effect of vericiguat on left ventricular (LV) reverse remodeling in patients with reduced LV ejection fraction (LVEF) with or without guideline-directed medical therapy, known as quadruple medical therapy, remains undetermined., Methods and Results: This study comprised 73 heart failure (HF) patients with reduced LVEF (<45%) from 5 institutions in Japan. Echocardiography was performed before and 6.1±3.9 months after administration of vericiguat. LV reverse remodeling was observed in all patients (LV end-diastolic volume 156.1±52.6 vs. 139.3±60.0 mL; P<0.001; LV end-systolic volume 108.1±41.2 vs. 91.8±51.2 mL; P<0.001; LVEF 31.8±7.4 vs. 37.6±12.3 %; P<0.001). LV reverse remodeling was also observed in 54 patients who could not undergo quadruple medical therapy for several reasons. Moreover, the incidence of cardiovascular events was also similar for patients who received or did not receive quadruple medical therapy (log-rank P=0.555)., Conclusions: Significant LV reverse remodeling was observed in HF patients with reduced LVEF following administration of vericiguat. LV reverse remodeling was also observed in patients who could not receive quadruple medical therapy, thus making administration of vericiguat a potential new approach for treatment of these patients., Competing Interests: H. Tanaka received remuneration from AstraZeneca plc, Ono Pharmaceutical Company, Limited. Pfizer Inc, Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Boehringer Ingelheim GmbH, Abbott Japan LLC, and Novartis International AG. K.H. has received research funding from Daiichi Sankyo Company, Limited, Actelion Pharmaceuticals Japan, Terumo Corporation, Abbott Vascular Japan, Otsuka Pharmaceutical Company, Limited, Kowa Company, Limited, Takeda Pharmaceutical Company Limited, Nihon Medi-Physics Company Limited, Novartis Pharma Company Limited, Bayer Company Limited, Biotronic Japan Company Limited, FUJIFILM Toyama Chemical Company Limited, Medtronic Japan Company Limited, Sysmex Company Limited. The remaining authors have no conflicts of interest to declare., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Objective: We investigated whether or not a history of multiple percutaneous coronary interventions (PCIs) is associated with clinical outcomes after surgery for ischemic mitral regurgitation. Methods: A total of 309 patients with chronic ischemic mitral regurgitation and left ventricular ejection fraction ≤40% who underwent restrictive mitral annuloplasty were classified as follows: patients with no or 1 previous PCI (nonmultiple PCI group [n = 211]) and patients with 2 or more previous PCIs (multiple PCIs group [n = 98]). Mean follow-up duration was 53 ± 40 months. Results: Before surgery, there were no intergroup differences in patient demographic characteristics except for lower estimated glomerular filtration rate in patients with multiple PCIs. These patients underwent concomitant coronary artery bypass grafting less frequently with a lower number of distal anastomoses (P

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).

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. [ABSTRACT FROM AUTHOR]

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/m2), 272 (32%) in quintile 2 (65-95 mL/m2), 247 (29%) in quintile 3 (95-125 mL/m2), 151 (18%) in quintile 4 (125-155 mL/m2), and 93 (11%) in quintile 5 (>155 mL/m2). 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. [ABSTRACT FROM AUTHOR]

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 (LASr). 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 LASr, was observed in survivors compared to non-survivors (43 [29–64] % vs. 8 [2–28] %, P < 0.001, respectively). After multivariate analysis, delta LASr 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 LASr 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. [ABSTRACT FROM AUTHOR]

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. 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). 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. [Display omitted] • What is already known: Vericiguat reduced cardiovascular death or hospitalization for heart failure in the patients with worsening heart failure (WHF) in VICTORIA study. • What is unknown: Little is known about the effects of vericiguat on right ventricular dysfunction associated with HFrEF. • What this study adds: Vericiguat improved RV-PA coupling and induced LV reverse remodeling. The treatment effects were independent of the quadruple therapy and WHF. • Clinical implications: Patients with HFrEF may benefit from early starting of vericiguat to prevent progression of biventricular adverse remodeling. [ABSTRACT FROM AUTHOR]

Hypo-attenuated leaflet thickening (HALT) of transcatheter aortic valves is detected on multidetector computed tomography (MDCT) and reflects leaflet thrombosis. Whether HALT affects left ventricular (LV) reverse remodeling, a favorable effect of LV afterload reduction after transcatheter aortic valve implantation (TAVI) is unknown. The aim of this study was to examine the association of HALT after TAVI with LV reverse remodeling. In this multicenter case–control study, patients with HALT on MDCT were identified, and patients without HALT were propensity matched for valve type and size, LV ejection fraction (LVEF), sex, age and time of scan. LV dimensions and function were assessed by transthoracic echocardiography before and 12 months after TAVI. Clinical outcomes (stroke or transient ischemic attack, heart failure hospitalization, new-onset atrial fibrillation, all-cause mortality) were recorded. 106 patients (age 81 ± 7 years, 55% male) with MDCT performed 37 days [IQR 32–52] after TAVI were analyzed (53 patients with HALT and 53 matched controls). Before TAVI, all echocardiographic parameters were similar between the groups. At 12 months follow-up, patients with and without HALT showed a significant reduction in LV end-diastolic volume, LV end-systolic volume and LV mass index (from 125 ± 37 to 105 ± 46 g/m2, p = 0.001 and from 127 ± 35 to 101 ± 27 g/m2, p < 0.001, respectively, p for interaction = 0.48). Moreover, LVEF improved significantly in both groups. In addition, clinical outcomes were not statistically different. Improvement in LVEF and LV reverse remodeling at 12 months after TAVI were not limited by HALT. [ABSTRACT FROM AUTHOR]

Background: Aortic valve neocuspidization (AVNeo) has emerged as a promising aortic valve procedure, and is expected to have a larger effective orifice area (EOA) than commercially available bioprostheses. It is, however, unclear which indices could facilitate left ventricular (LV) reverse remodeling after AVNeo. The aim of this study is to verify the impact of global left ventricular afterload on the LV reverse remodeling following AVNeo.Methods: Data-available consecutive 38 patients (median age, 77; interquartile range, 72.8-82.0) undergoing AVNeo for severe aortic stenosis were enrolled in this study. Preoperative and the last follow-up echocardiographic data were retrospectively analyzed including the valvuloarterial impedance (Zva), a marker of global LV afterload. Reduction in LV geometry index (LVGI) and relative wall thickness (RWT) were used as an indicator for LV reverse remodeling.Results: The Zva reduced in 24 patients (63.2%) during the follow-up period (median, 12 months). Reduction in Zva significantly correlated to improvement of LV geometry (LVGI (r = 0.400, p = 0.013) and RWT (r = 0.627, p < 0.001)), whereas increase in EOA index did not significantly correlate to LVGI (r = 0.009, p = 0.957), or RWT (r = 0.105, p = 0.529)). The reduction in Zva was the multivariate predictor of LV reverse remodeling.Conclusions: Low global LV afterload led to significant LV reverse remodeling even after AVNeo, which could achieve better valve performance than the conventional bioprostheses. [ABSTRACT FROM AUTHOR]

Background: Left ventricular (LV) structural and functional changes have been reported in patients with aortic stenosis (AS) who have undergone transcatheter aortic valve implantation (TAVI); however, the relationship between change in LV structure and systolic function and tissue characteristics assessed via cardiovascular magnetic resonance imaging (CMRI) post-TAVI has been not fully elucidated. This study aimed to investigate this relationship in patients with severe AS who underwent TAVI and CMRI., Methods: In this retrospective study, 65 patients who underwent TAVI and CMRI at the 6-month follow-up were analyzed. The relationship between percent changes in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and LV mass (LVM) (⊿LVEDV, ⊿LVESV, ⊿LVEF, and ⊿LVM) and those in the native T1 value (⊿native T1) was analyzed using a correlation analysis. Moreover, extracellular volume fraction (ECV) value changes were analyzed., Results: The ⊿native T1 significantly decreased from 1292.8 (1269.9-1318.4) ms at pre-TAVI to 1282.3 (1262.6-1310.2) ms at the 6-month follow-up (P = 0.022). A significant positive correlation between ⊿LVEDV, ⊿LVESV, and ⊿LVM and ⊿native T1 (r = 0.351, P = 0.004; r = 0.339, P = 0.006; r = 0.261, P = 0.035, respectively) and a tendency toward a negative correlation between ⊿LVEF and ⊿native T1 (r = -0.237, P = 0.058) were observed. The ECV value increased significantly from 26.7 % (25.3-28.3) to 28.2 % (25.7-30.5) (P = 0.002)., Conclusions: The decrease in native T1 might be associated with LV reverse remodeling. Evaluating structural and functional changes using CMRI may be useful for patient management., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis., Competing Interests: This work was supported by grants from the SENSHIN Medical Research Foundation (to Dr Nomura), the Japan Foundation for Applied Enzymology (to Drs Ko, Nomura, and Dai), the Kanae Foundation for the Promotion of Medical Science (to Dr Nomura), the MSD Life Science Foundation (to Dr Nomura), the Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), the Tokyo Biomedical Research Foundation (to Dr Nomura), the Astellas Foundation for Research on Metabolic Disorders (to Dr Nomura), the Novartis Foundation (Japan) for the Promotion of Science (to Dr Nomura), the Japanese Circulation Society (to Drs Ko and Nomura), the Takeda Science Foundation (to Drs Ko and Nomura), the Cell Science Research Foundation (to Dr Nomura), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Dr Nomura), the Japan Heart Foundation (to Dr Ko), and the Daiichi-Sankyo Foundation of Life Science (to Dr Nomura); a Grant-in-Aid for Scientific Research (A) (to Dr Nomura); a Grant-in-Aid for Scientific Research (S) (to Dr Komuro); the UTEC-UTokyo FSI Research Grant Program (to Dr Nomura); the JST FOREST Program (grant JPMJFR210U) (to Dr Nomura); a Japan Society for the Promotion of Science Grant-in-Aid for Japan Society for the Promotion of Science fellow (23KJ0434) (to Dr Dai) and AMED JP23ek0109600h0002 (to Dr Ko); and JP20ek0109487, JP18km0405209, JP21ek0109543, JP21tm0724601, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011, JP23tm0724607, JP23gm4010020, JP23tm0524009, JP23tm0524004, JP23jf0126003, and JP24ek0109755 (to Drs Nomura and Komuro). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

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. [ABSTRACT FROM AUTHOR]

Background Cardiac fibrosis plays a crucial role in the pathogenesis of dilated cardiomyopathy (DCM). HE4 (human epididymis protein 4) is a secretory protein expressed in activated fibroblasts that exacerbates tissue fibrosis. In the present study, we investigated the clinical utility of HE4 measurement in patients with DCM and its pathophysiological role in preclinical experiments in vivo and in vitro. Methods and Results We measured serum HE4 levels of 87 patients with DCM. Endomyocardial biopsy expressed severe fibrosis only in the high HE4 group (P

• 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: Coronary collateral circulation (CCC) is linked to myocardial remodeling severity in patients with chronic ischaemic heart disease (IHD). However its effect on left ventricular reverse remodeling (LVRR) in patients with chronic IHD underwent coronary artery bypass surgery (CABG) has never been reported. Purpose of this study was to investigate the effect of CCC grade on the LVRR event in patients with chronic IHD underwent CABG. Methods: This prospective cohort study was performed in patients with chronic IHD underwent CABG. The CCC was classified using Rentrop collateral score, i.e low CCC grade (Rentrop score 0 and 1) and high CCC grade (Rentrop score 2 and 3). LVRR event was defined as a reduction in left ventricular end systolic volume (LVESV) of 10% or more, measured by a 3D echocardiography at 1.5 months post CABG compared to the baseline before CABG. Results: A total of 22 patients (81.8% male) with mean of age 58.6 years old were enrolled. LVRR occurred in 50% patients. LVRR event was significantly higher in the patients with high CCC grade than the low CCC grade patients (p=0.009). The high CCC grade increased LVRR event independently (odds ratio=26.67; relative risk=6.93). Conclusions: High coronary collateral circulation may increase left ventricular reverse remodeling event in patients with chronic ischemic heart disease underwent coronary artery bypass surgery. Keywords: coronary collateral circulation; left ventricular reverse remodeling; chronic ischaemic heart disease; coronary artery bypass surgery; 3D echocardiography.

• The number of elderly heart failure patients is rapidly increasing in Japan. • The management of elderly heart failure patients is a critical issue. • Our findings showed that the indication of cardiac resynchronization therapy (CRT) should not be determined by age. • CRT is a useful tool in heart failure pandemic era. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Background: Elevations of resting heart rate (HR) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) are often missed, resulting in some patients with an indication for ivabradine reportedly being missed. Methods and Results: We studied 30 relatively stable HFrEF outpatients, and ivabradine was administered when regular follow-up echocardiography showed a resting HR ≥75 beats/min. Significant left ventricular reverse remodeling was observed 10.1±3.9 months after administration of ivabradine. Conclusions: This finding may well make this procedure a potential new approach for preventing worsening of HF for relatively stable patients with HFrEF., Competing Interests: H.T. has received remuneration from AstraZeneca plc, Ono Pharmaceutical Company, Limited, Pfizer Inc, Otsuka Pharmaceutical Co., Ltd, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Boehringer Ingelheim GmbH, Abbott Japan LLC, and Novartis International AG., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Determination of the prognosis and treatment outcomes of dilated cardiomyopathy is a serious problem due to the lack of valid specific protein markers. Using in-depth proteome discovery analysis, we compared 49 plasma samples from patients suffering from dilated cardiomyopathy with plasma samples from their healthy counterparts. In total, we identified 97 proteins exhibiting statistically significant dysregulation in diseased plasma samples. The functional enrichment analysis of differentially expressed proteins uncovered dysregulation in biological processes like inflammatory response, wound healing, complement cascade, blood coagulation, and lipid metabolism in dilated cardiomyopathy patients. The same proteome approach was employed in order to find protein markers whose expression differs between the patients well-responding to therapy and nonresponders. In this case, 45 plasma proteins revealed statistically significant different expression between these two groups. Of them, fructose-1,6-bisphosphate aldolase seems to be a promising biomarker candidate because it accumulates in plasma samples obtained from patients with insufficient treatment response and with worse or fatal outcome. Data are available via ProteomeXchange with the identifier PXD046288.

Background: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established., Purpose: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation., Study Type: Prospective, single-center, two arm, interventional vs. nonintervention observational study., Population: Forty-four patients (male N = 30; median age 68 [59-75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing "watchful waiting" (WW)., Field Strength/sequence: 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots)., Assessment: Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi)., Statistical Tests: Included Student t-test/Mann-Whitney test/Fisher's exact test, Bland-Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05., Results: While Bland-Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement -36 mL to 65 mL), than between 4DF-MR and TTE (bias -8; limits of agreement -106 mL to 90 mL) and PMRI and TTE (bias -23; limits of agreement -105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89)., Data Conclusion: This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation., Evidence Level: 2 TECHNICAL EFFICACY: Stage 5., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Abstract Background Left ventricular reverse remodeling (LVRR) in patients with ST-elevation myocardial infarction (STEMI) is associated with a good prognosis. Serum levels of ADAMTS-7 might be used for the prognosis of STEMI. This study aimed to investigate the relationship between serum ADAMTS-7 levels and LVRR. Methods This was a prospective study of 104 patients with STEMI who underwent revascularization and 63 controls. ADAMTS-7 serum levels were measured on days 1, 3, and 7 and in months 1 and 6 after STEMI. A decrease ≥ 15% of the left ventricular end-systolic volume at 6 months was defined as LVRR. Results The serum levels of ADAMTS-7 in patients with LVRR were lower than those without LVRR (3.84 ± 2.26 vs. 5.02 ± 2.54, P = 0.032) 7 days after STEMI and the difference between day 7 and day 1 (ΔADAMTS-7) was even significantly lower (− 1.31 ± 0.94 vs. − 0.30 ± 0.22, P = 0.021). Multivariate analysis showed that ΔADAMTS-7(day 7 minus day 1) was independently associated with LVRR (OR = − 0.322, 95% CI = − 0.996 to − 0.074, P = 0.028). Receiver operating characteristic (ROC) curve analysis showed that LVRR could be predicted (sensitivity 89%, specificity 82%, and area under the curve 0.896) when ΔADAMTS-7(day 7 minus day 1) was

Sudden cardiac death and arrhythmia-related events in patients with non-ischaemic dilated cardiomyopathy (NICM) have been significantly reduced over the last couple of decades as a result of evidence-based pharmacological and non-pharmacological therapeutic strategies. Nevertheless, the arrhythmic stratification in patients with NICM remains extremely challenging, and the simple indication based on left ventricular ejection fraction appears to be insufficient. Therefore, clinicians need to go beyond the current criteria for implantable cardioverter-defibrillator implantation in the direction of a multiparametric evaluation of arrhythmic risk. Several parameters for arrhythmic risk stratification, ranging from electrocardiographic, echocardiographic, imaging-derived and genetic markers, are crucial for proper arrhythmic risk stratification and a multiparametric evaluation of risk in patients with NICM. In particular, integration of cardiac magnetic resonance parameters (mostly late gadolinium enhancement) and specific genetic information (ie, presence of LMNA, PLN, FLNC mutations) appears fundamental for proper implementation of the current arrhythmic risk stratification. Finally, a novel approach focused on both arrhythmic risk and prediction of left ventricular reverse remodelling during follow-up might be useful for effective multiparametric and dynamic arrhythmic risk stratification in NICM. In the future, a complete and integrated evaluation might be mandatory to implement arrhythmic risk prediction in patients with NICM and to discriminate the competing risk between heart failure-related events and life-threatening arrhythmias. [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]

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/dtmax 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. [ABSTRACT FROM AUTHOR]

Background: The course of newly diagnosed dilated cardiomyopathy (DCM) varies from persistent reduction of left ventricular ejection fraction (LVEF) to recovery or even worsening. The aim of the present study was to examine the prognostic value of selected biomarkers with regard to changes in LVEF. Methods: Main inclusion criterion was LVEF ≤45% with exclusion of coronary artery or valvular heart disease. The primary endpoint was LVEF ≤35% in the follow-up echocardiogram. Galectin-3, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) were related to the endpoint. Results: Data from 80 DCM patients (55 male, mean age 53 years) were analyzed. Median LVEF was 25% (IQR 25–30). The endpoint was met for 24 patients (30%). These had higher baseline levels of galectin-3 (median 20.3 ng/mL [IQR 14.3–26.9] vs. 14.7 ng/mL [IQR 10.9–17.7], p = 0.007) and NT-proBNP (3089 pg/mL [IQR 1731–6694] vs. 1498 pg/mL [IQR 775–3890]; p = 0.004) in univariate Cox regression analysis. ROC analysis revealed that CRP (median 0.4 mg/dL [IQR 0.2–1.2]) was also related to the endpoint (p = 0.043). Conclusion: Higher levels of galectin-3, NT-proBNP, and CRP were associated with LVEF ≤35% in our cohort. An approach utilizing a combination of biomarkers for patient management should be assessed in further studies. [ABSTRACT FROM AUTHOR]

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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.

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. [ABSTRACT FROM AUTHOR]