Reverse Cardiac Remodeling Research Articles

Impact of Transcatheter Mitral Valve Repair on Left Ventricular Remodeling in Secondary Mitral Regurgitation: A Meta-Analysis

ABSTRACT Background: Secondary mitral regurgitation (MR) arises from left ventricular (LV) dilatation and remodeling, and commonly is treated with transcatheter mitral valve repair. We examined the impact of MitraClip on reverse cardiac remodeling in patients with severe, symptomatic secondary MR. Methods:: An electronic search was performed through January 2018 for studies that reported cardiac chamber dimensions prior to and after treatment with MitraClip in patients with secondary MR. The mean difference (MD) with 95% CI was calculated using fixed or random inverse variance models. Outcomes of interest were changes in LV end-systolic and end-diastolic volumes (LVESV, LVEDV) and dimensions (LVESD, LVEDD). Secondary outcomes included left atrial (LA) volume, systolic pulmonary artery pressure (sPAP) and LV ejection fraction (LVEF). Results: A total of 16 studies with 1,266 patients were included in the present analysis. The weighted mean follow-up period (±SD) was 11.5 ± 7.2 months. MitraClip was associated with significant reduction in LVEDV (−14.24 ml, 95% CI [−22.53, −5.94], p = 0.0008), LVESV (−7.67 ml, CI [−12.30, −3.03], p = 0.001), LVEDD (−2.92 mm [−3.65, −2.19 mm], p < 0.00001), and LVESD (−1.92 mm [−2.92, −0.92], p = 0.0002). MitraClip was also associated with reduction in LA volume (−16.36 ml [23.23, −9.49 ml], p < 0.00001) and sPAP (−6.93 mmHg [−8.76, −5.10], p < 0.00001), and a significant increase in LVEF (+ 2.78% [0.91, 4.66], p = 0.004). Conclusions: In patients with severe symptomatic secondary MR, MitraClip is associated with modest, but favorable LV and LA reverse remodeling. The impact of these changes on clinical outcomes deserves further study.

EP26 PRELIMINARY RESULTS OF LAST GENERATION SURGICAL BIOPROSTHESES IN SMALL AORTIC ANNULI: TRIFECTA VS INTUITY

Background and Aim: Aortic valve replacement (AVR) in patients with small aortic annulus is associated with increased risk of patient-prosthesis mismatch. Results of 19–21 Trifecta vs Intuity bioprostheses in patients with annular size &lt;21 mm are compared. Methods: Between 2013 and 2017,we retrospectively analyzed 25 (22 women,76.8 ±6.6 years) Trifecta AVR patients vs 26 (23 women, 78.6 ± 4.7 years) Intuity AVR patients.Combined procedures and reinterventions were excluded.Body surface area, left ventricular mass index and Euroscore-II were not different (p:0.68, 0.92 and 0.96 respectively). Results: Cardiopulmonary-bypass time was 108.6 ± 22.5 and 84.4 ± 20.5 minutes(p: 0.012);aortic cross-clamp time was 79.3 ± 14.6 and 60.73 ± 15.3 minutes in the Trifecta and in the Intuity group respectively(p:0.001). There wasn’t significant difference in postoperative transvalvular gradients.Lenght of hospital stay and major complications were not significantly different between the two groups.Follow-up is still ongoing. At 3.5 ± 1.2 years,41.1% of patients were followed-up. Until now, no significant difference neither in term of mortality nor in major complications have been observed.Peak pressure gradients were 29.2 ± 11.5 and 20.7 ± 5.9 mmHg (p:0.04);mean 16.2 ± 6.4 and 11 ± 3.03 mmHg (p: 0.02).Effective orifice area (EOA) was 1.43 ± 0.24 and 1.3 ± 0.2 cm2(p:0.5).There is no significant difference in reverse cardiac remodeling (left ventricular mass index 134.4 vs 124.4 g/m2.p:0.43). Conclusions: Trifecta and Intuity prostheses provide excellent hemodynamic results in small aortic annulus AVR. Operative times with Intuity were significantly lower. EOA was similar in both groups,however Trifecta presented significantly higher gradients at follow-up. Preliminary data need to be confirmed: completion of follow-up (July 2018) could provide stronger evidence to these first surveys.

Cytokines profile of reverse cardiac remodeling following transcatheter aortic valve replacement

ObjectivePrevious studies have suggested that cytokines and growth factors may predict ventricular recovery following aortic valve replacement (AVR). The primary objective of this study was to identify cytokines that predict ventricular recovery following transcatheter AVR (TAVR). MethodsWe prospectively enrolled 121 consecutive patients who underwent TAVR. Standard echocardiographic assessment at baseline, 1-month and 1-year after TAVR included left ventricular (LV) mass index (LVMI) and global longitudinal strain (GLS). Blood samples were obtained at the time of the procedure to measure cytokines using a 63-plex Luminex platform. Partial least squares-discriminant analysis was performed to identify cytokines associated with ventricular remodeling and function at baseline as well as 1 year after TAVR. ResultsThe mean age was 84 ± 9 years, with a majority of male subjects (59%), a mean LVMI of 120.4 ± 45.1 g/m2 and LVGLS of −13.0 ± 3.2%. On average, LV mass decreased by 8.1% and GLS improved by 20.3% at 1 year following TAVR. Among cytokines assayed, elevated hepatocyte growth factor (HGF) emerged as a common factor significantly associated with worse baseline LVMI and GLS as well as reduced ventricular recovery (p < 0.005). Other factors associated with ventricular recovery included a select group of vascular growth factors, inflammatory mediators and tumor necrosis factors, including VEGF-D, ICAM-1, TNFβ, and IL1β. ConclusionWe identified a network of cytokines, including HGF, that are significantly correlated with baseline LVMI and GLS, and ventricular recovery following TAVR.

CMR quantitation of change in mitral regurgitation following transcatheter aortic valve replacement (TAVR): impact on left ventricular reverse remodeling and outcome

Current echocardiographic data reporting the impact of concomitant mitral regurgitation (MR) on outcome in patients who undergo transcatheter aortic valve replacement (TAVR) are conflicting. Using cardiovascular magnetic resonance (CMR) imaging, this study aimed to assess the impact of MR severity on cardiac reverse remodeling and patient outcome. 85 patients undergoing TAVR with CMR pre- and 6 m post-TAVR were evaluated. The CMR protocol included cines for left (LV) and right ventricular (RV) volumes, flow assessment, and myocardial scar assessment by late gadolinium enhancement (LGE). Patients were dichotomised according to CMR severity of MR fraction at baseline (‘non-significant’ vs ‘significant’) and followed up for a median duration of 3 years. Forty-two (49%) patients had ‘significant MR’ at baseline; they had similar LV and RV size and function compared to the ‘non-significant MR’ group but had greater LV mass at baseline. In those with significant MR at baseline, 77% (n = 32) had a reduction in MR post-TAVR, moving them into the ‘non-significant’ category at 6-months, with an overall reduction in MR fraction from 34 to 17% (p < 0.001). Improvement in MR was not associated with more favourable cardiac reverse remodeling when compared with the ‘non-improvers’. Significant MR at baseline was not associated with increased mortality at follow-up. Significant MR is common in patients undergoing TAVR and improves in the majority post-procedure. Improvement in MR was not associated with more favourable LV reverse remodeling and baseline MR severity was not associated with mortality.

Abstract 542: Manipulation of Beta Adrenergic Receptor in Pressure-Overloaded Murine Hearts Mimics Adverse Cardiac Remodeling and Reverse Remodeling

Background: Adverse cardiac remodeling (ACR) during pressure overload is a major concern in development of heart failure (HF). Cardiac reverse remodeling (CRR) normally occurs following induction of beta-receptor blockade and is linked to improved prognosis of HF. However, the detailed and regulatory mechanisms of both ACR and CRR remain to be fully elucidated. To solve these issues, a novel highly reproducible model that mimics these pathophysiological conditions is needed. Methods and results: We explored suitable experimental conditions for establishing a highly reproducible model that mimics adverse cardiac remodeling. To examine suitable durations of transverse aortic constriction (TAC) before one-week infusion of ISO (3mg/kg/day), mice were distributed into three groups according to TAC durations. Proportion of adverse cardiac remodeling was 44.4% (4 of 9) in one-week, 60.0% (6 of 10) in two-week, and 91.7% (11 of 12) in three-week TAC groups. Next we examined adequate dose of ISO infusion after three weeks of TAC. Proportion of adverse cardiac remodeling was 37.5% (3 of 8) in 1mg/kg/day, 83.3% (5 of 6) in 3mg/kg/day, and 100% (8 of 8) in 10mg/kg/day group. But infusion of 10mg/kg/day ISO caused an increase in systolic BP. Thus we identified 3-week TAC and subsequent one-week ISO (3mg/kg/day) infusion as a suitable model for ACR. To identify molecular signatures of failing hearts of our ACR model, we performed RNA-Seq analyses. We found the up-regulated genes were mainly related to fibrosis including Fbn1 , C1qtnf6 and Loxl2 and the down-regulated genes associated with mitochondrial functions including, Uqcrc1 , Ndufs3 , and Idh2 . Next, we followed the changes in cardiac function after ceasing ISO to investigate CRR. Decreased LVFS gradually recovered to baseline within 7 weeks after cessation of ISO and exhibited CRR. Gene expression signature of CRR hearts was almost identical to that of TAC hearts without ISO infusion. Conclusions: Our model exhibits a transition to adverse cardiac remodeling and subsequent reverse remodeling with high reproducibility. This novel mouse model might add new insights into these cardiac remodeling.

Foreword

Progressive thinning and dilation of the LV due to ischemic heart failure (IHF) increases wall stress and myocardial oxygen consumption. Injectable biopolymers implanted in the myocardial wall have been used to increase wall thickness to reduce chamber volume, decrease wall stress, and improve cardiac function. We sought to evaluate the efficacy of a biopolymer (Algisyl-LVR) to prevent left ventricular (LV) remodeling in a swine model of IHF.IHF was induced in 11 swine by occluding the marginal obtuse branches of the left circumflex artery. Eight weeks later, Algisyl-LVR was injected into the LV myocardial free wall in five of the 11 animals. Echocardiographic examinations were done every 2 weeks for 16 weeks.Within eight weeks of treatment, the ejection fraction increased from 30.5% ± 7.7% to 42.4% ± 3.5% (treated group) vs. 37.3% ± 3.8% to 34.3% ± 2.9% (control), p < 0.01. Stroke volume increased from 18.5 ± 9.3 mL to 41.3 ± 13.3 mL (treated group) vs. 25.4 ± 2.3 mL to 31.4 ± 5.3 mL (control), p < 0.05. Wall thickness in end-diastole of the infarcted region changed from 0.69 ± 0.06 cm to 0.81 ± 0.13 cm (treated group) vs. 0.73 ± 0.09 cm to 0.68 ± 0.11 cm (control), p < 0.05. Sphericity index remained almost unchanged after treatment, although differences were found at the end of the study between both groups (p < 0.001). Average myofiber stress changed from 16.3 ± 5.8 kPa to 10.2 ± 4.0 kPa (treated group) vs. 15.2 ± 4.8 kPa to 17.9 ± 5.6 kPa (control), p < 0.05.Algisyl-LVR is an effective strategy that serves as a micro-LV assist device to reduce stress and hence prevent or reverse maladaptive cardiac remodeling caused by IHF in swine.

Adverse effects of left ventricular electrical dyssynchrony on cardiac reverse remodeling and prognosis after aortic valve surgery

BackgroundElectrical dyssynchrony (ED) is one of the important contributing mechanisms in the progression of heart failure. We hypothesized that ED would interfere with cardiac reverse remodeling and affect prognosis after aortic valve surgery. MethodsA total of 411 consecutive patients (233 males, mean age 65±11 years) who underwent aortic valve surgery were retrospectively analyzed. The patients were divided into two groups according to the presence of ED [Group 1: no ED (n=382, 93%), Group 2: ED (n=29, 7%)]. ED was defined as either left ventricular bundle branch block, or electrical pacing rhythm. Cardiac reverse remodeling was assessed at 1 year after surgery by the changes in left ventricular ejection fraction (LVEF), LV end-systolic volume (LVESV), and left atrial volume index (LAVI). The primary endpoint was a composite of hospitalization for heart failure, and all-cause mortality. ResultsAt 1 year after surgery, group 2 showed lower LVEF (58±15% vs. 64±9%, p=0.044), and higher LAVI (42±18ml/m2 vs. 33±13ml/m2, p=0.018) than group 1. However, LVESV values (55±38ml vs. 42±24ml, p=0.076) were not significantly different. In particular, in patients with reduced preoperative LVEF, the LVEF was markedly increased in group 1 but not in group 2 after 1 year. During a median follow-up of 39 months, group 2 showed a worse clinical outcome than group 1 (20.7% vs. 7.6%, p=0.031). After adjusting for confounding factors in the multivariate analyses, age [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.06–1.16, p<0.001] and the presence of ED (HR 2.43, 95% CI 1.01–5.89, p=0.046) were found to be independent predictors of clinical outcomes. ConclusionsED after aortic valve surgery negatively affected cardiac remodeling and prognosis.

Gender Differences in Cardiac Reverse Remodeling in Mechanically Unloaded Hearts

Gender Differences in Cardiac Reverse Remodeling in Mechanically Unloaded Hearts

Extracellular volume fraction assessed using cardiovascular magnetic resonance can predict improvement in left ventricular ejection fraction in patients with dilated cardiomyopathy

T1 mapping using cardiac magnetic resonance (CMR) is useful for myocardial assessment. However, its prognostic value is not well defined. The aim of this study was to determine whether T1 mapping with CMR can predict reverse cardiac remodeling in patients with non-ischemic dilated cardiomyopathy (NIDCM). We also investigated the predictive prognostic value of T1 mapping with CMR in these patients. We included 33 patients with NIDCM admitted to Nippon Medical School Hospital between February 2012 and October 2015. All patients underwent CMR and echocardiography for clinical assessment within 1month of admission (13 ± 16days). Follow-up echocardiography was performed no sooner than 6months after the initial echocardiogram (536 ± 304days). We evaluated the correlations between native and post-contrast T1 values/extracellular volume fraction (ECV) and the difference in left ventricular ejection fraction (ΔLVEF) determined at baseline and follow-up echocardiography. No correlation was noted between ΔLVEF and native (p = 0.150, r = - 0.256) or post-contrast T1 values (p = 0.956, r = - 0.010). However, a significant and substantial correlation was found between ΔLVEF and ECV (p = 0.043, r = - 0.355). Four patients were hospitalized for heart failure (HF), but no cardiovascular-related deaths occurred over a median follow-up period of 34months (interquartile range 25-49months). Kaplan-Meier curves stratified by the median value of ECV were created. The higher ECV groups experienced a significantly higher incidence of HF-related hospitalization (p = 0.0159). ECV measured by CMR can predict improvements in LVEF in patients with NIDCM. In addition, ECV may be a predictive factor for HF-related hospitalization.

Efficacy of intramyocardial injection of Algisyl-LVR for the treatment of ischemic heart failure in swine

BackgroundProgressive thinning and dilation of the LV due to ischemic heart failure (IHF) increases wall stress and myocardial oxygen consumption. Injectable biopolymers implanted in the myocardial wall have been used to increase wall thickness to reduce chamber volume, decrease wall stress, and improve cardiac function. We sought to evaluate the efficacy of a biopolymer (Algisyl-LVR) to prevent left ventricular (LV) remodeling in a swine model of IHF. MethodsIHF was induced in 11 swine by occluding the marginal obtuse branches of the left circumflex artery. Eight weeks later, Algisyl-LVR was injected into the LV myocardial free wall in five of the 11 animals. Echocardiographic examinations were done every 2weeks for 16weeks. ResultsWithin eight weeks of treatment, the ejection fraction increased from 30.5%±7.7% to 42.4%±3.5% (treated group) vs. 37.3%±3.8% to 34.3%±2.9% (control), p<0.01. Stroke volume increased from 18.5±9.3mL to 41.3±13.3mL (treated group) vs. 25.4±2.3mL to 31.4±5.3mL (control), p<0.05. Wall thickness in end-diastole of the infarcted region changed from 0.69±0.06cm to 0.81±0.13cm (treated group) vs. 0.73±0.09cm to 0.68±0.11cm (control), p<0.05. Sphericity index remained almost unchanged after treatment, although differences were found at the end of the study between both groups (p<0.001). Average myofiber stress changed from 16.3±5.8kPa to 10.2±4.0kPa (treated group) vs. 15.2±4.8kPa to 17.9±5.6kPa (control), p<0.05. ConclusionsAlgisyl-LVR is an effective strategy that serves as a micro-LV assist device to reduce stress and hence prevent or reverse maladaptive cardiac remodeling caused by IHF in swine.

Cardiac remodelling after valvular replacement in patients with aortic stenosis: A substudy from Translink

Reverse cardiac remodelling is a major goal of aortic valve replacement (AVR). Global longitudinal strain (GLS) currently allows a more sensitive evaluation of systolic function than left ventricle ejection fraction (LVEF). The European Translink FP7 project prospectively included patients with aortic stenosis scheduled for surgical or percutaneous AVR. The present substudy included patients enrolled in Nantes University Hospital. Patients were separated in two groups according to baseline left ventricle (LV) GLS value (normal ≤ or altered > −16%). Changes in LV GLS and cardiac morphology were evaluated 6 months after AVR. Two hundred patients (64% men, mean age 74 ± 9 years) were included and the follow up at 6 months was completed in 127. LVEF at baseline was 62 ± 10% and GLS −16.1 ± 3.7%. Patients with impaired GLS at baseline ( n = 85, 43%) were more often diabetics and obese, and had higher NT-proBNP levels. Cardiac cavities remodelling was more pronounced, LVEF was moderately decreased (57.1 ± 10.9% vs. 65.9 ± 7.3%; P < 0.001), and valvulo-arterial impedance was higher. These patients experienced a significant improvement in GLS at 6 months (−15.3 ± 3.8% vs. −12.9 ± 2.3%; P < 0.001), in contrast with patients with normal GLS at baseline (-18.7 ± 1.6% vs. −18.1 ± 2.6%; P = 0.07). Baseline LVEF and septal E/Ea were significantly associated with GLS value at 6 months in multivariate analysis. There was no significant change in left atrium size but a decrease in E/Ea at 6 months. Despite a significant decrease in pulmonary artery pressure, there was a significant alteration of right ventricle strain at 6 months (−20.7 ± 4.7% vs. −23.2 ± 5.8%; P < 0.001), in correlation with tricuspid annulus dilatation ( Fig. 1 ). Left ventricle presented a significant reverse remodelling after surgical or percutaneous AVR, especially in patients with altered GLS before procedure. This favourable LV remodelling contrast with unfavourable right cavities remodelling.

Bariatric Surgery-Induced Cardiac and Lipidomic Changes in Obesity-Related Heart Failure with Preserved Ejection Fraction.

ObjectiveTo determine the effects of gastric bypass on myocardial lipid deposition and function and the plasma lipidome in women with obesity and heart failure with preserved ejection fraction (HFpEF).MethodsA primary cohort (N=12) with HFpEF and obesity underwent echocardiography, magnetic resonance spectroscopy before, and 3- and 6-mos after bariatric surgery. Plasma lipidomics were performed on pre- and 3-mo post-surgery in the primary cohort and confirmed in a validation cohort (N=22).ResultsAfter surgery-induced weight loss, Minnesota Living with Heart Failure questionnaire scores, cardiac mass, and liver fat decreased (P < 0.02, < 0.001, = 0.007); echo-derived e′ increased (P = 0.03), but cardiac fat was unchanged. Although weight loss was associated with decreases in many plasma ceramide and sphingolipid species, plasma lipid and cardiac function changes did not correlate.ConclusionsSurgery-induced weight loss in women with HFpEF and obesity is associated with improved symptoms, reverse cardiac remodeling and improved relaxation. While weight loss associated with plasma sphingolipidome changes, cardiac function improvement was not associated with lipidomic or myocardial triglyceride changes. Our study results suggest that gastric bypass ameliorates obesity-related HFpEF and that cardiac fat deposition and lipidomic changes may not be critical to its pathogenesis.

Cardiovascular response to prescribed detraining among recreational athletes.

Exercise-induced cardiac remodeling (EICR) and the attendant myocardial adaptations characteristic of the athlete's heart may regress during periods of exercise reduction or abstinence. The time course and mechanisms underlying this reverse remodeling, specifically the impact of concomitant plasma volume (PV) contraction on cardiac chamber size, remain incompletely understood. We therefore studied recreational runners ( n = 21, age 34 ± 7 yr; 48% male) who completed an 18-wk training program (~7 h/wk) culminating in the 2016 Boston Marathon after which total exercise exposure was confined to <2 h/wk (no single session >1 h) for 8 wk. Cardiac structure and function, exercise capacity, and PV were assessed at peak fitness (10-14 days before) and at 4 wk and 8 wk postmarathon. Mixed linear modeling adjusting for age, sex, V̇o2peak, and marathon finish time was used to compare data across time points. Physiological detraining was evidenced by serial reductions in treadmill performance. Two distinct phases of myocardial remodeling and hematological adaptation were observed. After 4 wk of detraining, there were significant reductions in PV (Δ -6.0%, P < 0.01), left ventricular (LV) wall thickness (Δ -8.1%, <0.05), LV mass (Δ -10.3%, P < 0.001), and right atrial area (Δ -8.2%, P < 0.001). After 8 wk of detraining, there was a significant reduction in right ventricle chamber size (end-diastolic area Δ = -8.0%, P < 0.05) without further concomitant reductions in PV or LV wall thickness. Abrupt reductions in exercise training stimulus result in a structure-specific time course of reverse cardiac remodeling that occurs largely independently of PV contraction. NEW & NOTEWORTHY Significant reverse cardiac remodeling, previously documented among competitive athletes, extends to recreational runners and occurs with a distinct time course. Initial reductions in plasma volume and left ventricular (LV) mass, driven by reductions in wall thickness, are followed by contraction of the right ventricle. Consistent with data from competitive athletes, LV chamber volumes appear less responsive to detraining and may be a more permanent adaptation to sport.

Percutaneous repair of mitral valve regurgitation in patients with severe heart failure: comparison with optimal medical treatment

Background: Occurrence of severe mitral valve (MV) regurgitation (MR) is an independent negative predictor of mortality in patients with severe systolic heart failure (HF). This study examines clinical effects and cardiac reverse remodelling in patients with severe systolic HF receiving percutaneous mitral valve repair (PMVR) using MitraClip in comparison to patients receiving optimal medical therapy only.Methods: Between 2010 and 2014, 86 patients (Society of Thoracic Surgeons score: 10.5% ± 1.2%) with severe HF (left ventricular [LV] ejection fraction; LVEF: 25% ± 2%; LV endsystolic diameter [LVESD]: 55 ± 3 mm) and severe MR received PMVR using MitraClip. Cardiac reverse remodelling and clinical parameters were compared to HF patients with severe MR (from our HF outpatient clinic; n = 69; LVEF: 26% ± 1.4%; LVESD: 53 ± 2 mm) receiving optimal medical therapy (OMT) only. All patients received stable OMT and were characterised by echocardiography, 6-minwalk-distance test and cardiac biomarkers within a 24 months observation period.Results: PMVR in patients with end-stage HF and severe MR resulted in reduction of MR and significant additional cardiac reverse remodelling (LVEF: 26 ± 1.4 vs. 33% ± 2%, p < .05; LVESD: 53 ± 2 vs. 47 ± 2 mm, p < .05) over the 24 months observation period as compared to pharmacologically-only managed comparators.Conclusions: Both OMT and PMVR cause cardiac reverse remodelling and relief of symptoms in patients with HF and severe MR. PMVR results in significant additional cardiac reverse remodelling compared to pharmacologically-only managed patients.

Abstract 20932: Dynamic Regulation of Myocardial Long Noncoding RNAs in Human Heart Failure and Reverse Remodeling With Left Ventricular Assist Device Support

Introduction: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression and have been implicated in various biological processes. Modulating lncRNA levels could be a plausible strategy for the treatment of heart failure (HF), however the specific lncRNAs responsible for cardiac reverse remodeling remain largely unknown. Hypothesis: Myocardial lncRNAs mediate reverse remodeling through cis -regulation of the neighboring mRNAs Methods: RNA sequencing was performed using total RNA isolated from failing human myocardium before (n=21) and after (n=12) left ventricular assist device (LVAD) implantation as well as from non-failing controls (n=5). Mapped reads for all GENCODE v26 lncRNAs were calculated. Differentially regulated mRNAs and lncRNAs were identified using a fold-change cut-off of 2 and a false discovery rate of 5%. Pearson correlation coefficient was used to determine the relationship between lncRNA and neighboring mRNAs. Results: 81 incident HF and 47 reverse remodeling lncRNAs were identified (Figure 1A). 46 HF lncRNAs (56.8%) were normalized following LVAD support and showed reciprocal regulation in the pre- vs. post-LVAD myocardium (Figure 1B). Recovery lncRNAs included recently described Myheart (originating in the MYH7 locus) as well as novel lncRNAs (NPPA-AS1, RORB-AS1, lnc-TECRL). Majority of the antisense, intergenic, and intronic myocardial lncRNAs demonstrated a positive correlation with neighboring genes suggesting cis -regulation by lncRNAs during cardiac reverse remodeling (Figure 1C). Conclusions: Myocardial lncRNAs are dynamically regulated during myocardial remodeling (HF) and reverse remodeling with LVAD support. Mechanical unloading is accompanied by partial normalization of the pathological lncRNA signature. Further studies will determine mechanisms by which neighboring protein coding genes are regulated by lncRNAs in the failing human heart.

Percutaneous repair of severe mitral valve regurgitation secondary to chordae rupture in octogenarians using MitraClip.

The aim of this study was to assess feasibility and clinical effectiveness of the MitraClip device in octogenarians suffering from severe mitral valve regurgitation due to chordae rupture. The MitraClip procedure is a suitable technique in high-risk surgical patients to achieve safe and effective percutaneous repair of mitral valve regurgitation. Octogenarians show cumulative risk and social aspects hindering mitral valve surgery. No data exists regarding the use of the MitraClip device in high-risk octogenarians suffering from mitral valve chordae rupture. Between October 2009 and March 2017 98 high-risk octogenarians (society of thoracic surgeons score [STS]: 9.7% ± 0.8) with mitral valve prolapse and consecutively chordae rupture were treated with the MitraClip after interdisciplinary discussion. Successful mitral valve repair was achieved in 91% of the octogenarians. Repair of the mitral valve caused immediate and significant reduction of dyspnoea (NYHA class: 3.5 ± 0.4 vs 2.0 ± 0.3; P < 0.001), cardiac reverse remodeling (LVESD: 39 ± 0.8 vs 35 ± 0.8; P < 0.01) and amelioration of cardiac biomarkers (NTproBNP (4884 ± 52 ng/L vs 2473 ± 210 ng/L; P < 0.05,). Effects were stable over the 12 months observation period. None of our patients died intraprocedurally. Percutaneous repair of chordae rupture is feasible and safe in high-risk octogenarians. The MitraClip should be considered to repair severe mitral valve regurgitation due to mitral valve chordae rupture in high-risk octogenarians after interdisciplinary discussion even facing a challenging anatomy.

O11-3 - Early Administration of Mineralocorticoid Receptor Antagonist Is Useful for Cardiac Reverse Remodeling in Asymptomatic Patients with Dilated Cardiomyopathy

Background: Cardiac reverse remodeling (CRR) is considered to be one of surrogate markers of favorable prognosis in dilated cardiomyopathy (DCM). The administration of mineralocorticoid receptor antagonist (MRA) with ACE inhibitor and beta blocker is recommended to reduce future cardiac events in all symptomatic heart failure patients with reduced ejection fraction. However, little is known about the efficacy of MRA for asymptomatic heart failure patients. We aimed to investigate the association between early administration of MRA and CRR in asymptomatic DCM patients. Methods: We enrolled 74 DCM patients classified as NYHA I in this retrospective cohort study. All patients were divided into two groups; MRA(+) group (n = 33) and MRA(-) group (n = 41). CRR was defined as an absolute increase in left ventricular ejection fraction ≧10% accompanied by a decrease in left ventricular end-diastolic diameter >10% as assessed by echocardiography at 12 months. Results: As for baseline characteristics, the mean of left ventricular ejection fraction and end-diastolic diameter was 36% and 61 mm, respectively. The administration rate of ACE inhibitors/ARBs and was 82% and 81%. Thirty-three (45%) patients were treated with MRA. The rate of CRR was significantly higher in MRA(+) group than in MRA(-) group (58% vs 27%, P = .007). Conclusions: Early administration of MRA is useful for CRR in asymptomatic NYHA I patients with DCM, which may potentially result in a good prognosis.

Abstract P292: Reversal of Cardiac Remodeling After Surgical Intervention Leads to Distinct Cardiac Function Outcomes

Hypertension is the leading cause of cardiovascular diseases Nevertheless diagnosed hypertension can be controlled and monitored with adequate drug regimens. Yet once cardiac hypertrophy is established, a number of patients develop diastolic cardiac dysfunction resulting from cardiac remodeling with fibrosis and cell death. The present study aims to test the hypothesis that animals with aortic stenosis for five weeks can restore cardiac function after the removal of the aortic constriction. Male mice with 10 weeks of age were randomized in three groups Sham , Rem , and Tac . After five weeks of the establishment of cardiac hypertrophy the aortic constriction was removed and the animals were followed for additional five weeks Rem . The positive control group Tac remained with the clip until ten weeks. Echocardiography was performed after 72 hours of the removal of the five weeks stenosis Rem and at the end of ten weeks. We also used cutoff points based on sham group for the ejection fraction EF≥45% and the ratio of E wave per e’ E/e’≤35 . The Rem group was separated into two outcomes according to the presence of dysfunction. Results were expressed as mean ± standard error of the mean SEM. Statistical analyses were performed and p≤0.05 were considered statistically significant. Septum thickness increased after five weeks of stenosis in both Rem 0.812±0.01mm and Tac 0.764±0.02mm groups as compared to sham group 0.675±0.01mm p≤0.05. Left ventricle mass was significantly different in Sham vs Tac 73.98±2.40mg vs 111.79±11.81mg p&lt;0.0001 After 10 weeks the REM group did not present any hypertrophy markers. Among 18 animals of Rem group, 9 had reduced EF compared to sham after 5 weeks 36.97±1.87%vs52,74±4.17% p&lt;0.0001 and after 10 weeks 49±1.13%vs40±1.06% p&lt;0.0001 constituting an occurrence of systolic problems of 50%. When we analyzed E/e’ 13 animals presented diastolic dysfunction and an increased ratio compared to sham animals 41.07±1.12vs30.79±1.95 p&lt;0.05 at 5 weeks. Therefore, the occurrence of diastolic dysfunction reached 72%. The proposed model induced hypertrophy. Despite that, only half the Rem animals had a reduction in ejection fraction, whereas most developed diastolic dysfunction. These findings open a new path for the investigation of these distinct outcomes

246 - Phenotype of Super-Responders to Stem Cell Therapy for Non-Ischemic Dilated Cardiomyopathy

Background: The POSEIDON-DCM trial reported a marked increase in ejection fraction (EF) in non-ischemic dilated cardiomyopathy (NIDCM) patients receiving allogeneic mesenchymal stem cells (MSC), with half of the patients transitioning from HFrEF to heart Failure with recovered EF HFrecEF (defined by EF increasing to > 40%). Here we sought clinical factors predictive of this response and correlates of this recovery. Methods: POSEIDON-DCM (n = 34) patients were divided into 2 groups: Super-responders EF > 40 (n = 9; baseline EF: 32.1 ± 10.5%, EDV: 277.1 ± 71.5 mL), or low-responders EF < 40 (n = 15; baseline EF: 23.9 ± 9.75%, EDV: 382.7 ± 174.5mlL). Ten patients were excluded due to absence of follow-up CT/MRI imaging. Parameters measured at baseline, 6 and 12 months after MSC injection included sphericity index (SI), ejection fraction (EF) and end diastolic (EDV) and systolic (ESV) volume as measured by cardiac CT or MRI, and functional parameters such as MLHFQ score, 6-min walk distance (6MWD), and NYHA classification. Results: EF increased at 12 months by 15.0 ± 2.9 units (P = .001) in the EF > 40 group, and by 2.2 ± 1.7 units (P = .22) in the EF < 40 group (P < .0001 between groups). Importantly, the two groups were indistinguishable at baseline with regard to EF, age, gender, duration of disease, medication use, cardiac volumes or functional parameters. The increase in EF in super responders was driven by a profound decrease in cardiac volumes. EDV -62.5 ± 33.4 mL in the EF > 40 group vs +6.5 ± 10.2 mL in the EF < 40 group (P = .02 between groups); and ESV -75.8 ± 27.6 mL in the EF > 40 group (P = .02) vs -2.5 ± 8.6 mL in the EF < 40 group (P = .005 between groups). Reverse cardiac remodeling was evident by sphericity index. End Systolic SI decreased -0.1 ± 0.04 in the EF > 40 group (P = .03) vs +0.007 ± 0.02 in the EF < 40 group (P = .7) (P = .0003 between groups). Functional capacity and QOL consistently improved to a greater extent in the EF > 40 group: 6 minute walk distance improved 52 ± 2m (P = .04) in the EF > 40 group vs 16 ± 2m in the EF < 40 group (P = .3; P = .058 between groups) at 12 months. MLHFQ decreased -21.5 ± 8.5 (P = .006) in the EF > 40 group vs -16.1 ± 4.4 in the EF < 40 group (P = .02; P = .03 between groups) at 12 months. NYHA class decreased in both groups (P < .004) with no between group significance. Conclusions: The POSEIDON-DCM trial revealed a NIDCM subpopulation highly responsive to treatment with intramyocardial MSCs, who are not discernable at baseline by phenotypic or demographic characteristics. High responders have greatly enhanced improvements in functional capacity and reversing cardiac remodeling. Future studies to identify this subpopulation will have major implications for the management of advanced cardiomyopathic syndromes.

Postprocedural Changes of Tricuspid Regurgitation After MitraClip Therapy for Mitral Regurgitation

The effect of percutaneous mitral valve repair using the MitraClip system on tricuspid regurgitation (TR) has not been well investigated. We retrospectively analyzed 102 consecutive patients who underwent the successful MitraClip procedure, and who also had a preprocedural and 1-year follow-up transthoracic echocardiography. TR severity was graded by standard guideline-recommended criteria. At 1 year after the MitraClip procedure, the degree of TR regressed (at least 1 grade) in 23% of the patients, was unchanged in 62% of the patients, and progressed in 16% of the patients. Compared with patients in the other groups, the patients with TR regression had a greater severity of TR at baseline. The TR regression group showed a significant reduction in the systolic pulmonary artery pressure (sPAP) (49 ± 13 to 37 ± 11 mm Hg, p <0.05), a right-sided cardiac reverse remodeling (right ventricular diameter: 41 ± 7 to 39 ± 7 mm, tricuspid annular diameter: 48 ± 8 to 46 ± 9 mm, both p <0.05), and an increase in the right ventricular fractional area change (38 ± 7 to 40 ± 7%, p <0.05). In the multivariate analysis, the decrease in sPAP was the only independent parameter change associated with TR regression. In conclusion, TR regression was observed in 23% of the patients after the successful MitraClip procedures, and favorable echocardiographic parameter changes were detected in this group. Only a reduction in sPAP was independently associated with TR regression.