Left Ventricle Reverse Remodeling Research Articles

Characterization of biventricular alterations in myocardial (reverse) remodelling in aortic banding-induced chronic pressure overload

Aortic Stenosis (AS) is the most frequent valvulopathy in the western world. Traditionally aortic valve replacement (AVR) has been recommended immediately after the onset of heart failure (HF) symptoms. However, recent evidence suggests that AVR outcome can be improved if performed earlier. After AVR, the process of left ventricle (LV) reverse remodelling (RR) is variable and frequently incomplete. In this study, we aimed at detecting mechanism underlying the process of LV RR regarding myocardial structural, functional and molecular changes before the onset of HF symptoms. Wistar-Han rats were subjected to 7-weeks of ascending aortic-banding followed by a 2-week period of debanding to resemble AS-induced LV remodelling and the early events of AVR-induced RR, respectively. This resulted in 3 groups: Sham (n = 10), Banding (Ba, n = 15) and Debanding (Deb, n = 10). Concentric hypertrophy and diastolic dysfunction (DD) were patent in the Ba group. Aortic-debanding induced RR, which promoted LV functional recovery, while cardiac structure did not normalise. Cardiac parameters of RV dysfunction, assessed by echocardiography and at the cardiomyocyte level prevailed altered after debanding. After debanding, these alterations were accompanied by persistent changes in pathways associated to myocardial hypertrophy, fibrosis and LV inflammation. Aortic banding induced pulmonary arterial wall thickness to increase and correlates negatively with effort intolerance and positively with E/e′ and left atrial area. We described dysregulated pathways in LV and RV remodelling and RR after AVR. Importantly we showed important RV-side effects of aortic constriction, highlighting the impact that LV-reverse remodelling has on both ventricles.

Mechanisms of recurrent regurgitation after transapical off-pump mitral valve repair with neochord implantation†.

The aim of this study was to describe possible mechanisms of recurrent mitral regurgitation (MR) in patients who have been treated with the NeoChord procedure. Patients presenting with recurrent severe or moderate MR were categorized as Not Expected Surgical-Like Result (NESLR)-Redo and NESLR-MR2 [NESLR reintervention or moderate MR (2+), respectively]. NESLR patients were stratified by onset (intraoperative, perioperative 24 h-30 days, or early 30 days to follow-up), by MR jet direction (central or eccentric) and by jet orientation (anterior or posterior). Specific mechanisms of NESLR were analysed. Fifty-two patients were identified with 13 (25%) categorized as NESLR-Redo, and 39 (75%) as NESLR-MR2. NESLR-Redo patient stratification included: intraoperative = 2 patients (1.2%), both eccentric anteriorly directed jets; perioperative = 7 patients (4.2%), all eccentric with 3 anteriorly and 4 posteriorly directed jets; and early = 4 patients (2.4%), 1 central, 3 eccentric, 2 posteriorly and 1 anteriorly directed jets. NESLR-MR2 patient stratification included: perioperative = 2 patients (5.1%), both eccentric, 1 anteriorly and 1 posteriorly directed jets; and early = 37 patients (94.9%), 4 central, 33 eccentric, 22 anteriorly and 11 posteriorly directed jets. Possible mechanisms of recurrent MR were identified as: patient selection (17.3%), technical issues (28.8%), progression of baseline disease (15.4%), left ventricle reverse remodelling (1.9%), excessive over-tensioning (35.8%) and PML curling (30.8%). The mechanisms of recurrent MR after the NeoChord procedure can be determined. Understanding recurrent MR mechanisms has led to improvements in procedural standardization and ad hoc prevention strategies that have been widely adopted since our initial clinical experience.

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

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

"RFEF" and mitral regurgitation jet direction: surrogate markers for likelihood of left ventricle reverse remodeling in patients with moderate chronic ischemic mitral regurgitation.

Surgical management of moderate chronic ischemic mitral regurgitation (CIMR) is controversial. We propose a simplified classification of moderate CIMR based on regurgitant fraction (RF), ejection fraction (EF), and jet direction (central/eccentric) to predict left ventricle (LV) remodeling and identify patient subsets which need mitral valve (MV) repair along with coronary artery bypass grafting (CABG). In this prospective controlled study (n = 210), patients with moderate CIMR were randomized. Group I (n = 106) underwent off-pump CABG alone while group II (n = 104) underwent CABG + MV repair. The product of regurgitation fraction and ejection fraction ("RFEF") was taken as a surrogate for myocardial reserve. The cut-off defined was 0.12; patients with RFEF ≤ 0.12 were categorized as the "bad" and those with RFEF > 0.12 as the "good" subset. The patients were further subdivided on the basis of their mitral regurgitation (MR) jet direction (central/eccentric). The percentage improvement in left ventricular end-systolic volume index (LVESVI) and MR grade were recorded 6monthly. Analysis of the continuous variable "RFEF" in conjunction with jet direction was performed. At 12months, the patient in good subset with central direction of jet showed improvement in LVESVI % in both groups (p = 0.428), while the patients in bad subset with eccentric direction of jet showed significantly higher improvement in LVESVI %, group II as compared to group I (p = 0.004). This study thus identifies "RFEF" as a surrogate for reverse remodeling capacity. In association with MR jet direction, predicts the subset of moderate CIMR patients most likely to have maximum LVESVI and MR grade reduction.

YIA-CS1-2 - Comparison between Cardiac Magnetic Resonance and Myocardial Ultrastructural Features in Patients with Dilated Cardiomyopathy to Predict Recovery of Cardiac Function

Background: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging is a useful modality to detect myocardial fibrosis. However, some patients with dilated cardiomyopathy (DCM) are not accompanied by LGE. Methods: Endomyocardial biopsy from left ventricle (LV) was performed in 55 consecutive DCM patients (55.5 ± 13.1 years, 82% men), at their initial presentation with decompensated HF. Ultrastructural features of cardiomyocytes were detected by electron microscopy. LV functional changes over time by trans-thoracic echocardiography were examined. Definition of LV reverse remodeling (LVRR) is increasing LV ejection-fraction (EF) from >10% to a final value of >35% at 12 months. Results: During median follow-up of 2.1 years, 12 patients (22%) were readmitted for HF recurrence. Myofilament lysis, which are apparent in degenerated cardiomyocytes of DCM, were identified in 41 (72%), and autophagic vacuoles in cardiomyocytes were identified in 24 (42%). Multiple-regression analysis showed that independent predictors of LVRR were higher Body-Mass Index (P = .031), usage of Aldosterone-Receptor Antagonist (P = .013), autophagy (P = .003), and absence of LGE (P = .015) and myofilament lysis (P = .012). Independent predictors of readmission due to HF recurrence were C-reactive protein (hazard-ratio [HR], 1.995; 95% confidence-interval [CI], 1.065–3.737), myofilament lysis (HR, 14.854; 95% CI, 1.725–127.878), and absence of autophagic vacuoles (HR, 0.055; 95% CI, 0.006–0.483). Conclusions: Ultrastructural features are useful to predict not only their prognosis, but also LVRR in patients with DCM.

Resolution of Mitral Regurgitation With Left Ventricular Assist Device Support

Cardiac valve disease is common in patients with end-stage heart failure undergoing left ventricular assist device implantation (LVAD). The aim of this study was to determine if preoperative mitral regurgitation (MR) affects outcomes and hemodynamics in patients after LVAD implantation. From March 2006 through May 2015, 238 consecutive patients underwent LVAD implantation. Patient cohorts included less than moderate to severe MR (< moderate-severe, n= 195) and greater than or equal to moderate to severe MR (≥ moderate-severe, n= 43). Demographics, operative characteristics, postoperative outcomes, hemodynamic and echocardiographic data, and resolution of MR were compared at 30 and 180 days post-LVAD. Significant hemodynamic improvements were seen in central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, left ventricular ejection fraction, and left ventricular end-diastolic diameter, irrespective of preoperative MR severity. Significant resolution of MR occurred across both cohorts, with only 4 of 168 (2.4%) patients with ≥ moderate-severe MR at 180 days post-LVAD. There were no differences in complications or survival between MR severity cohorts postoperatively. LVAD implantation unloads the left ventricle to promote left ventricle reverse remodeling and correct functional MR across all severity levels. The resolution of MR is sustained at 180 days post-LVAD. These results coupled with no survival difference with uncorrected MR between < moderate-severe MR and ≥ moderate-severe MR makes concomitant mitral valve repair or replacement at the time of LVAD implantation unnecessary.

Left atrium in cardiac resynchronization therapy: Active participant or innocent bystander

BackgroundCardiac resynchronization therapy (CRT) is an established treatment for patients with advanced heart failure that results in improvement of left ventricle (LV) systolic function and LV reverse remodeling. This may have a positive effect on the size and the function of the left atrium (LA). We assessed the LA function, dimensions, and volumes before and after CRT implantation. MethodsA total of 37 patients with mean age of 55.3±9.64years including 11 (29.7%) females, having symptomatic heart failure [ejection fraction (EF) <35%, left bundle branch block >120ms, with New York Heart Association III or ambulatory class IV] were enrolled, and underwent CRT implantation. M-mode, two-dimensional (2D) echocardiography, tissue Doppler imaging, and 2D strain (ɛ) imaging were done assessing LV volumes, ejection fraction, and diastolic function, LA diameter, area, maximal and minimal volumes, LA EF, and longitudinal strain (ɛ). Patients were reassessed after 3months. A reduction in LV end-systolic volume of ≥10% was defined as volumetric responders to CRT. Patients with decompensated New York Heart Association class IV, sustained atrial arrhythmias, rheumatic or congenital heart diseases, nonleft bundle branch block, and those who were poorly echogenic, were excluded. ResultsTwenty-four (64.8%) patients were volumetric responders (group A). Both groups were matched regarding demographic, clinical, electrocardiographic, and echocardiographic criteria apart from the LA dimension and volumes which were significantly lower in the responders group prior to CRT. At the end of the follow-up, only the responders group had further significant reduction in LA diameter (41.6±1.67 vs. 43.88±1.82mm, p<0.01), maximal volume (62.2±18.3 vs. 73.04±21.78ml, p<0.01), minimal volume (32.6±12.3 vs. 41.8±13.97, p<0.01), together with a significant increase in LA EF (48.3±11.3 vs. 41.99±13.9, p<0.01), positive longitudinal strain (16.59%±5.89 vs. 12.45%±6.12, p<0.01), and negative longitudinal strain (−3.3±1.9 vs. −1.62±1.2, p<0.01) compared to baseline readings, a finding that was not present in the nonresponders group. In addition, atrial fibrillation was significantly higher in the nonresponders group. Baseline LA diameter and volumes were found to be independent predictors of response to CRT by multivariate analysis. ConclusionsCRT induces LA anatomic, electrical, and structural reverse remodeling that could be assessed by conventional 2D echocardiography and 2D (ɛ) strain imaging. LA dimension and volumes were independent predictors of response to CRT and can help in selection of candidates for it.

Abstract P253: Carvedilol Benefits in Hypertensive Cardiomyopathy

Left ventricle remodeling is a common consequence of uncontrolled hypertension. Hypertension treatment including renin-angiotensin-aldosterone system inhibition and beta-blockers offers cardiac protection. Carvedilol uses in cardiomyopathy from different etiology have shown good results in left ventricle reverse remodeling. There is a lack of information regarding carvedilol use in hypertensive cardiomyopathy. The main objective in this study was to evaluate the use of carvedilol in hypertensive patients with reduced left ventricle ejection fraction. We evaluate 98 subjects with reduced left ventricle ejection fraction (55 years age, 59 males, 64 white, 34 nonwhite) before and after at least six months of carvedilol use. Clinical data, laboratory tests, and echocardiogram were evaluated at least 6 months before and after carvedilol was added to the treatment. Other causes of cardiomyopathy, including coronary artery disease, were excluded. A hundred percent of patients was taking diuretic and renin-angiotensin-aldosterone system inhibitors. Twenty eight percent were using statins, 19% were using antidiabetic drugs, and 29% were taking digoxin. Blood pressure and heart rate (144/92 mmHg, 84 bpm) decreased significantly after (130/82 mmHg, 70 bpm) carvedilol treatment. Ejection fraction improved in 68.5% patients. Let ventricle diastolic diameter decreased from 62 to 56 mm, left ventricle systolic diameter decreased from 53 to 42 mm, left ventricle mass index decreased from 145 to 129 g/m 2 , left ventricle relative posterior wall increased from 0.32 to 0.36. Carvedilol, in addition to antihypertensive drugs, showed improvement in hemodynamic parameters, and in echocardiographic structural and functional parameters in hypertensive cardiomyopathy patients.

Impact of transcatheter aortic valve implantation on the left ventricular mass.

Aortic stenosis (AS) induces pressure overload of the left ventricle (LV) and results in left ventricular hypertrophy. The remodeling of the LV in patients with AS is a com-plex process including structural and functional disturbances. After aortic valve replacement, reverse remodeling of LV begins. The aim of this study was to evaluate the impact of transcatheter aortic valve ımplantation (TAVI) on LV mass (LVM) in early and mid-term follow-ups after the procedure. We enrolled consecutive 75 patients who underwent successful TAVI. Transthoracic echocardiography was performed prior to TAVI and at hospital discharge, in the 1st month and 6th month of the follow-ups. The mean LV ejection fraction improved significantly after TAVI (54.2 ± 15.0% to 57.3 ± 11.7%, p < 0.001). There were no significant changes between the baseline and discharge mean LVM and LVM index values (LVMI; p = 0.1). However, LVMI decreased significantly in the 1st month of follow-up compared to baseline (123.3 ± 20.3 to 127.9 ± 21.3 g/m², respectively, p < 0.001). Also, significant regression of LVM was observed at the 1st month of follow-up compared to baseline (228.3 ± 33.5 g vs. 236.5 ± 34.2 g, respectively, p < 0.001). Furthermore, the significant regression in both of LVM and LVMI continued at 1st and 6th months of the follow-ups (p < 0.001). A significant regression of LVM was observed after TAVI. These changes may have prognostic value in patients with severe AS.

Abstract 19622: Trans-apical Off-pump Mitral Valve Repair With Neochords Implantation: One Year Clinical and Echocardiographic Follow-up

Introduction: TOP-MINI is a new micro invasive surgical procedure to treat degenerative mitral valve regurgitation due to flail/prolapse. Hypothesis: This prospective single centre study sought to assess the safety and effectiveness of the TOP-MINI procedure up to one year follow-up. Methods: Clinical and Echocardiographic outcomes were evaluated at 1, 3, 6 months and 1 year follow-up for all patients underwent TOP-MINI procedure from November 2013 to March 2015. Procedural success was defined as residual MR≤2+ at any time. Results: Sixty-one patients were treated during study period. One year survival was 96.7±2.3%. Freedom from MR&gt;2+ is shown in figure 1 Panel A, Freedom from MR&gt;2+ according to valve anatomy (Type A isolated P2 disease, Type B posterior multisegment disease, Type C anterior or bileaflet and/or calcified disease) is shown in Figure 1 Panel B. Freedom from MR&gt;2+ according to STS risk profile is shown in Figure 2. The trend of Echocardiographic parameters is shown in Figure 3. Conclusions: TOP-MINI is a safe and effective procedure at 1 year FU. Residual MR is influenced by valve anatomy showing good results in Type A and B patients. Future techniques refinements are needed in order to improve outcomes of Type C patients. The lack of annuloplasty procedure does not influence negatively left ventricle reverse remodeling.

Hemodynamic device-based optimization in cardiac resynchronization therapy: concordance with systematic echocardiographic assessment of AV and VV intervals

Hemodynamic device-based optimization in cardiac resynchronization therapy: concordance with systematic echocardiographic assessment of AV and VV intervals M&aacute;rio M Oliveira, Luisa M Branco, Ana Galrinho, Nogueira da Silva, Pedro S Cunha, Bruno Valente, Joana Feliciano, Ricardo Pimenta, Ana Sofia Delgado, Rui Cruz Ferreira Santa Marta Hospital, Lisbon, Portugal Background: Inappropriate settings of atrioventricular (AV) and ventriculo-ventricular (VV) intervals can be one of the factors impacting response to cardiac resynchronization therapy (CRT). Optimal concordance of AV and VV intervals between echocardiographic-based assessment and a device-based automatic programming with a hemodynamic sensor was investigated, together with left ventricle (LV) reverse remodeling after 6 months of regular automatic device-based optimization.Methods: We evaluated blindly 30 systematic echocardiographic examinations during 6 months in 17 patients (12 men, 64&plusmn;10 years, in sinus rhythm and New York Heart Association class III; 76% with non-ischemic dilated cardiomyopathy, LV ejection fraction [LVEF] &lt;35%, QRS 130 milliseconds and LV dyssynchrony) implanted with the SonRtip lead and a cardioverter-defibrillator device. Dyssynchrony (AV, VV, or intraventricular) was evaluated by an experienced operator blinded to the device programming, using conventional echocardiography, tissue synchronization imaging, tissue Doppler imaging, radial strain, and 3D echocardiography.Results: Either no AV or VV dyssynchrony (n=11; 36.7%) or a slight septal or lateral delay (n=13; 43.3%) was found in most echocardiography examinations (80%). AV or VV dyssynchrony requiring further optimization was identified in one-fifth of the examinations (20%). At 6 months, 76.5% patients were responders with LV reverse remodeling, of which 69% were super-responders (LVEF &gt;40%). A statistically significant increase in LVEF was observed between baseline and 6 months post implant (P&lt;0.01). One patient died from non-cardiac causes.Conclusion: Concordance between echocardiographic methods and device-based hemodynamic sensor optimization was found in most examinations (80%) post CRT. After 6 months of systematic optimization with SonR, patients showed a statistically significant increase in LVEF, with a high rate of reverse remodeling. Keywords: cardiac resynchronization therapy, hemodynamic sensor, atrioventricular delay, interventricular delay, reverse remodeling

Sex Differences in Aortic Stenosis and Outcome Following Surgical and Transcatheter Aortic Valve Replacement.

Aortic stenosis is the commonest valve defect in the developed world and is associated with a high mortality once symptomatic. There is a difference in the way that male and female hearts remodel in the face of chronic pressure overload: women develop a concentrically hypertrophied, small cavity left ventricle (LV), whereas men are more prone to the development of eccentric hypertrophy. At a cellular level, there is an increase in collagen and metalloproteinase gene expression in males suggesting a different regulation of extracellular volume composition according to sex. Male hearts with aortic stenosis appear to have more fibrosis than their female comparators. The trigger for this appears to be in part related to estrogen receptor signaling, but other factors such as renin-angiotensin activation, nitric oxide, and circulating noradrenaline levels may also be implicated. Treatment options include surgical valve replacement (SAVR) and more recently transcatheter aortic valve replacement (TAVR). Female sex may be a risk factor for adverse outcome following SAVR and conversely appears to confer a survival advantage when undergoing TAVR. Whether the lower mortality seen following TAVR in women compared with men (despite their increased age and frailty) reflects their longer life expectancy, smaller annular size (and less post-TAVR aortic regurgitation), more favorable LV reverse remodeling, or more likely, a combination of these factors remains to be established.

Reduction in coronary microvascular resistance through cardiac resynchronization and its impact on chronic reverse remodelling of left ventricle in patients with non-ischaemic cardiomyopathy.

Left bundle branch block (LBBB) induces mechanical dyssynchrony, thereby compromising the coronary circulation in non-ischaemic cardiomyopathy. We sought to examine the effects of cardiac resynchronization therapy (CRT) on coronary flow dynamics and left ventricular (LV) function. Twenty-two patients with non-ischaemic cardiomyopathy (New York Heart Association class, III or IV; LV ejection fraction, ≤35%; QRS duration, ≥130 ms) were enrolled. One week after implantation of the CRT device, coronary flow velocity and pressure in the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCx) were measured invasively, before and after inducing hyperemia by adenosine triphosphate administration, with two programming modes: sequential atrial and biventricular pacing (BiV) and atrial pacing in patients with LBBB or sequential atrial and right ventricular pacing in patients with complete atrioventricular block (Control). We assessed hyperemic microvascular resistance (HMR, mean distal pressure divided by hyperemic average peak velocity) and the relationship between the change in HMR and mid-term LV reverse remodelling. Hyperemic microvascular resistance was lower during BiV than during Control (LAD: 1.76 ± 0.47 vs. 1.54 ± 0.45, P < 0.001; LCx: 1.92 ± 0.42 vs. 1.73 ± 0.31, P = 0.003). The CRT-induced change in HMR of the LCx correlated with the percentage change in LV ejection fraction (R = -0.598, P = 0.011) and LV end-systolic volume (R = 0.609, P = 0.010) before and 6 months after CRT. Cardiac resynchronization therapy improves coronary flow circulation by reducing microvascular resistance, which might be associated with LV reverse remodelling.

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure.

BackgroundThe data on the prognostic values of high sensitivity C-reactive protein (hsCRP) levels in patients with advanced symptomatic heart failure (HF) receiving cardiac resynchronization therapy (CRT) are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome.MethodsA total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF.ResultsDuring the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP (> 3 mg/L) prior to CRT was associated with a significant 2.39-fold increase (P = 0.006) in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels (–0.5 ± 4.1 mg/L reduction) compared with non-responders (1.7 ± 6.1 mg/L increase, P = 0.018). Compared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations (Log-rank P < 0.001). The echocardiographic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high.ConclusionsOur findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.

Gender-related clinical and echocardiographic outcomes at 30-day and 12-month follow up after MitraClip implantation in the GRASP registry.

To assess the influence of patients' gender on the outcomes of percutaneous edge-to-edge mitral valve repair (PMVR) using the MitraClip system. Although gender-related differences have been extensively documented in patients who undergo surgery for moderate-to-severe (3+) and severe (4+) mitral regurgitation (MR), studies assessing whether these differences exist after PMVR are lacking. Clinical and echocardiographic data through 12-month follow up from 171 consecutive patients whom underwent MitraClip implantation and were dichotomized by the gender (106 males and 65 females) were obtained. The primary safety endpoint was the incidence of major adverse events at 30 days and the primary efficacy endpoint was freedom from death, surgery for mitral valve dysfunction, or grade≥3+ MR at 12-month follow up. The primary safety endpoint was observed in four males (3.8%) and four females (6.2%) (P=0.358). Remarkable reduction in MR postprocedure was revealed in both groups, and these results were mostly sustained. Furthermore, left ventricle reverse remodeling and New York Heart Association (NYHA) functional class improvement were revealed in both groups, but females tended to demonstrate worse results over time (P=0.083). The primary efficacy endpoint obtained by Kaplan-Meier estimates was observed in 76.3 and 70.2%, respectively (log rank P=0.231). MitraClip implantation in patients with 3+ and 4+ MR is safe and efficacious until mid-term follow up, regardless of patients' gender. Despite improvement in NYHA functional class in both groups, female gender demonstrated a trend toward poorer results. Further validation of our findings is warranted.

Association of tricuspid regurgitation with clinical and echocardiographic outcomes after percutaneous mitral valve repair with the MitraClip System: 30-day and 12-month follow-up from the GRASP Registry.

The aim of this study was to evaluate the association of baseline tricuspid regurgitation (TR) on the outcomes after percutaneous mitral valve repair (PMVR) with the MitraClip system. Data from 146 consecutive patients with functional mitral regurgitation (MR) were obtained. Two different groups, dichotomized according to the degree of pre-procedural TR (moderate/severe, n = 47 and none/mild, n = 99), had their clinical and echocardiographic outcomes through 12-month compared. At 30-day, the primary safety endpoint was significantly higher in moderate/severe TR compared with none/mild TR (10.6 vs. 2.0%, P = 0.035). Marked reduction in MR grades observed post-procedure were maintained through 12 months. Although NYHA functional class significantly improved in both groups compared with baseline, it was impaired in moderate/severe TR compared with the none/mild TR group (NYHA > II at 30 day: 33.3 vs. 9.2%, P < 0.001; at 1 year: 38.5 vs. 12.3%, respectively, P = 0.006). Left ventricle reverse remodelling and ejection fraction improvement were revealed in both groups. The primary efficacy endpoint at 12-month determined by freedom from death, surgery for mitral valve dysfunction, or grade ≥ 3+ MR was comparable between groups, but combined death and re-hospitalization for heart failure rates were higher in the moderate/severe TR group. Multivariable Cox regression analysis demonstrated that baseline moderate/severe TR and chronic kidney disease were independent predictors of this combined endpoint. Although PMVR with MitraClip led to improvement in MR, TR, and NYHA functional class in patients with baseline moderate/severe TR, the primary safety endpoint at 30-day was impaired, while moderate/severe TR independently predicted death and re-hospitalization for heart failure at 12-month.

Cardiac resynchronization therapy restored ventricular septal myocardial perfusion and enhanced ventricular remodeling in patients with nonischemic cardiomyopathy presenting with left bundle branch block

Left bundle branch block (LBBB) causes intraventricular conductional delay, which results in left ventricle (LV) mechanical dyssynchrony. In the absence of coronary artery disease, patients with LBBB often have diminished accumulation of technetium-99m compounds at the myocardial septal area in electrocardiogram-gated single-photon emission computed tomography. To investigate whether cardiac resynchronization therapy (CRT) could improve septal myocardial perfusion, leading to favorable reverse remodeling. The study included all 26 patients with nonischemic cardiomyopathy eligible for CRT, who presented with LBBB, New York Heart Association class II-IV heart failure, and LV ejection fraction ≤35%. Single-photon emission computed tomography was performed at baseline and 6 months after CRT. Perfusion counts were measured at the ventricular septum and LV lateral free wall. Left ventricular end-systolic volume (LVESV) was measured by echocardiography to evaluate LV reverse remodeling by CRT. At baseline, a perfusion defect at the LV septal myocardial area was confirmed in 19 of 26 (73%) patients. In these patients, septal perfusion significantly increased 6 months after CRT (56.1% ± 22.8% vs 82.9% ± 21.2%; P < .001). LVESV reduction and improved septal perfusion index were positively correlated (r = .561; P = .012), whereas no correlation was found between LVESV reduction and the difference of QRS duration before and 6 months after CRT (r = .218; P = .371). The improvement in LV septal perfusion was associated with LV reverse remodeling. CRT could restore LV septal myocardial perfusion and ameliorate ventricular reverse remodeling in most patients with nonischemic cardiomyopathy and LBBB.

Predictors of improvement in diastolic function after transcatheter aortic valve implantation.

Aortic stenosis is associated with concentric left ventricle (LV) hypertrophy or remodeling resulting in impaired diastolic function and elevated left-sided filling pressure. We investigated the changes in LV geometry and LV filling hemodynamics, giving emphasis to parameters associated with changes in diastolic function after transcatheter aortic valve implantation (TAVI). Comprehensive diastolic assessment was performed before and six months after TAVI in 70 patients with severe aortic stenosis. Patients with any degree of mitral stenosis or >mild left-sided valvular regurgitation were excluded. In the entire cohort six months after TAVI, LV end-diastolic diameter increased (44.1±6 versus 45±6mm, P=0.02), whereas LV mass and relative wall thickness (RWT) decreased (270.1±76 versus 245.1±75g and 0.53±0.15 versus 0.46±0.1, respectively; P<0.0001 for both). Lateral e' increased (5.8±2 versus 6.6±3cm/s, P=0.03) and left atrium (LA) volume, E/e' ratio, and systolic pulmonary pressure decreased (88.1±30 versus 80±28cc, 18±7.8 versus 16.3±5.5, and 42.7±14.9 versus 38.7±12mmHg, respectively; P<0.05 for all), suggesting reduction in LA pressure. The improvement in LA volume and E/e' was almost exclusively seen in patients with LV hypertrophy before TAVI (P<0.05 both), as opposed to patients with concentric remodeling. In our preliminary study, TAVI resulted in LV and LA reverse remodeling, and improved LV relaxation and LA filling pressure in patients with severe aortic stenosis and concentric hypertrophy. Patients with concentric remodeling at baseline seem to have limited improvement in LV diastolic function and filling pressure following TAVI, but larger clinical trials would be required to conclude if they have no improvement at all.

Synthetic prostacyclin agonist, ONO1301, enhances endogenous myocardial repair in a hamster model of dilated cardiomyopathy: A promising regenerative therapy for the failing heart

Remodeling of the left ventricle (LV) in idiopathic dilated cardiomyopathy (IDCM) is known to be associated with multiple pathologic changes that endogenous factors, such as hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), protect against. Although a clinically relevant delivery method of these factors has not been established, ONO1301, a synthetic prostacyclin agonist, has been shown to upregulate multiple cardioprotective factors, including HGF and VEGF, invivo. We thus hypothesized that ONO1301 may reverse LV remodeling in the DCM heart. ONO1301 dose-dependently added to the normal human dermal fibroblasts and human coronary artery smooth muscle cells invitro, to measure the expression of HGF, VEGF, stromal cell-derived factor (SDF)-1, and granulocyte-colony stimulating factor (G-CSF), assessed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. δ-Sarcoglycan-deficient J2N-k hamsters, which is an established DCM model, were treated by epicardial implantation of an atelocollagen sheet with or without ONO1301 immersion or sham operation. ONO1301 dose-dependently upregulated expression of these 4 factors invitro. ONO1301 treatment, which induced dominant elevation of ONO1301 levels for 2 weeks, significantly preserved cardiac performance and prolonged survival compared with the other groups. This treatment significantly upregulated expressions of cardioprotective factors and was associated with increased capillaries, attenuated fibrosis, and upregulation of α-sarcoglycan in the DCM heart. ONO1301 atelocollagen-sheet implantation reorganized cytoskeletal proteins, such as α-sarcoglycan, increased capillaries, reduced fibrosis, and was associated with upregulated expression of multiple cardioprotective factors, leading to preservation of cardiac performance and prolongation of survival in the δ-sarcoglycan-deficient DCM hamster.

Impact of correction of ischemic mitral valve on left ventricular reverse remodeling

Background Chronic ischemic mitral regurgitation (IMR) is frequent complication of myocardial infarction. It is associated with high cardiovascular morbidity and mortality. We examined the effects of surgery of ischemic mitral valve on reverse remodeling of left ventricle, impact on functional state of patients after operation, assessment of early morbidity and mortality. Methods