First-in-human feasibility study of the aXess graft (aXess-FIH): 6-Month results.

OBJECTIVE: The creation of an arteriovenous fistula (AVF) is considered the most effective hemodialysis (HD) vascular access. For patients who are not suitable for AVF, arteriovenous grafts (AVGs) are the best access option for chronic HD. However, conventional AVGs are prone to intimal hyperplasia, stenosis, thrombosis, and infection. Xeltis has developed an AVG as a potential alternative to currently available AVGs based on the concept of endogenous tissue restoration. The results of the first 6-month follow-up are presented here. METHODS: The aXess first-in-human (FIH) study [NCT04898153] is a prospective, single-arm, multicenter feasibility study that evaluates the early safety and performance of the aXess Hemodialysis Graft. A total of 20 patients with end-stage renal disease were enrolled across six European investigational sites. RESULTS: At 6-months follow-up, all grafts were patent with primary and secondary patency rates were 80% and 100%, respectively. Three patients required a re-intervention to maintain graft patency, while one re-intervention was required to restore patency. One graft thrombosis and zero infections were reported. CONCLUSION: The expected advantages of the novel aXess Hemodialysis Graft over conventional AVGs would be evaluated by the analysis on long-term safety and effectiveness during the 5-year follow-up of the currently ongoing trial.

Oxygen Saturation Increase in Ischemic Wound Tissues after Direct and Indirect Revascularization.

BACKGROUND: The primary approach for treating ischemic wounds is restoring oxygen supply to the ischemic region. While direct angiosomal revascularization is often associated with better post-operative wound healing and limb salvage, its superiority over non-angiosomal revascularization remains controversial. This study aimed to compare intraoperative tissue oxygen saturation changes in ischemic zones following either direct or indirect revascularization in below-the-knee arteries. METHODS: This prospective observational study included patients undergoing direct and indirect below-the-knee endovascular revascularizations. Assignment to the groups was not randomized. Near-infrared spectroscopy was used to monitor rSO2 changes near the ischemic wounds intraoperatively. The changes were compared between the groups. RESULTS: 15 patients (50%) underwent direct angiosomal revascularization, while an equal number of patients underwent indirect revascularization. Overall, a statistically significant increase in regional oxygen saturation was observed after revascularization (p = 0.001). No statistically significant difference was found between the direct and indirect revascularization groups (p = 0.619). CONCLUSIONS: This study revealed a minor difference in the oxygen saturation increase between the angiosomal and non-angiosomal revascularization groups. Such a finding indicates that the clinical significance of angiosomal revascularization is negligible and might be concealed by confounding factors, such as the vessel diameter and outflow impact on the restenosis rate.

Validation of the Lithuanian Version of the Walking Impairment Questionnaire in Patients with Peripheral Arterial Disease.

Background and Objectives: The Walking Impairment Questionnaire (WIQ) is a short and simple tool to measure walking impairment for patients with peripheral arterial disease requiring no special equipment or trained staff. The aim of this study was to assess the validity and reliability of the culturally adapted Lithuanian WIQ version in patients with intermittent claudication. Materials and Methods: In total, 40 patients with intermittent claudication and ankle-brachial index < 0.90 participated in this study. Reliability and internal consistency of the questionnaire were assessed by the intra-class correlation coefficient (ICC) and Cronbach's alpha (α), respectively. Validity was determined by correlations between the WIQ scores and a subjective test (Quality of Life 5 Dimension Questionnaire 3 Level Version (EQ-5D-3L)) and objective tests (6 min walk test (6MWT), treadmill test, and ankle-brachial index). Results: The test-retest reliability was assessed as excellent with an intraclass correlation coefficient of 0.90. The values of Cronbach's alpha were 0.957 (I time) and 0.948 (II time) and indicated an excellent internal consistency. Statistically significant Spearman correlations were detected between the WIQ and walking distances on the 6MWT (rho 0.514, p < 0.001) and treadmill test (rho 0.515, p < 0.001). Higher WIQ scores were associated with longer walking distances and duration. Moderate negative and low negative correlations were found between the WIQ and EQ-5D-3L scores. Conclusions: The Lithuanian version of culturally adapted WIQ demonstrates reliability and validity for patients with intermittent claudication, supported by two different walking tests showing statistically significant moderate Spearman correlations.

Electrocardiographic Markers of Adverse Left Ventricular Remodeling and Myocardial Fibrosis in Severe Aortic Stenosis.

The optimal timing for aortic valve replacement (AVR) in aortic stenosis (AS) is still controversial and may be guided by markers of adverse left ventricular (LV) remodeling. We aim to assess electrocardiographic (ECG) strain in relation to LV remodeling and myocardial fibrosis. 83 severe AS patients underwent surgical AVR, with preoperative 12-lead ECG, cardiovascular magnetic resonance with T1 mapping and echocardiography with global longitudinal strain analysis. Collagen volume fraction (CVF) was measured in myocardial biopsies sampled during AVR. Patients with ECG strain had more severe AS, more advanced LV remodeling and evidence of heart failure. Patients with ECG strain had more diffuse fibrosis, as evident by higher mean native T1 values (974.8 ± 34 ms vs. 946.5 ± 28 ms, p < 0.001). ECG strain was the only predictor of increased LV mass index on multivariate regression analysis (OR = 7.10, 95% CI 1.46-34.48, p = 0.02). Patients with persistent ECG strain at 1 year following AVR had more advanced LV remodeling and more histological fibrosis (CVF 12.5% vs. 7.3%, p = 0.009) at baseline assessment. Therefore, ECG strain is a marker of adverse LV remodeling and interstitial myocardial fibrosis. Lack of improvement in ECG strain following AVR indicates more advanced baseline LV injury and higher levels of myocardial fibrosis.

The Early Effects on Tricuspid Annulus and Right Chambers Dimensions in Successful Tricuspid Valve Bicuspidization.

BACKGROUND: It is unclear to what degree of tricuspid annulus (TA) reduction is necessary to achieve good postoperative results in surgical bicuspidization. The study aimed to evaluate TA and right heart chamber's dimensions before and after heart surgery; and to compare TA parameters assessed by different modalities. METHODS: Forty patients underwent mitral valve surgery with or without concomitant tricuspid valve (TV) bicuspidization. Preoperative and postoperative measurements of TA dimensions were performed prospectively using two-dimensional (2D) and three-dimensional (3D) transthoracic echocardiography (TTE). Additionally, preoperative transesophageal echocardiography (TOE) was performed in the operating room prior to surgery. RESULTS: All patients had no or mild TR immediately after surgery. There was a significant reduction in 2D and 3D parameters of the TV and right chambers in the TV bicuspidization group. However, TV leaflets' tethering parameters did not change significantly. Preoperative 3D TTE measurements were smaller than those obtained through 3D TOE in the operation room, before surgery under general anesthesia. The 2D systolic apical 4Ch diameter and the parasternal short axis diameter mainly represent the 3D minor axis of the TA and are smaller than its 3D major axis. CONCLUSIONS: Although bicuspidization results in a one-third reduction of the TV area, tethering of the TV leaflets remains unchanged. Moreover, 3D TOE parameters of the TV under general anesthesia are larger than preoperative 3D TTE measurements. Conventional 2D measurements are insufficient for evaluating the maximum diameter of the TA.

A Comparison of the Catheter-Based Transapical and Surgical Treatment Modalities for Mitral Paravalvular Leak.

BACKGROUND: There is a lack of studies where the outcomes of mitral paravalvular leak treatment were compared between surgery and catheter-based closure. The aim of this study was to compare the outcomes of re-do surgery with transapical catheter-based paravalvular leak closure. METHODS: This is a retrospective observational study at a single institution; 76 patients were included. According to the treatment, two groups were formed: the "Surgical" group (49 patients after re-do surgery) and the "Catheter" group (27 patients after transapical catheter-based treatment). RESULTS: In-hospital myocardial infarction occurred in 9 (18%) cases in the "Surgical" group and none in the "Catheter" group, p = 0.018. Procedure-related life-threatening bleeding occurred in 9 (18%) patients in the "Surgical" group and none in the "Catheter" group, p = 0.018. Nine (18%) patients died in 30 days in the "Surgical" group, and none died in the "Catheter" group, p = 0.039. A mean follow-up was 3.3 years. No difference was found between the groups by the degree of residual paravalvular regurgitation either at discharge or at follow-up. During the follow-up, 19 (39%) patients died in the "Surgical" group and 2 (7%) among the "Catheter" patients. CONCLUSIONS: Transapical catheter-based closure of mitral paravalvular leak seems to be a safer treatment procedure than conventional re-do surgery, and the effectiveness of these procedures does not differ.

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study.

Myocardial fibrosis in aortic stenosis is associated with worse survival following aortic valve replacement. We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. A total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement and T1 mapping and global longitudinal strain analysis. Collagen volume fraction was measured in myocardial biopsies (71) that were sampled at the time of AVR. Results. CVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p<0.001). CVF median values were higher in LGE-positive versus LGE-negative patients [28.7% (19-33) vs 20.7% (15-30), respectively, p=0.040]. GLS was associated with invasively (CVF; r=-0.303, p=0.013) and non-invasively (native T1; r=-0.321, p<0.05) measured myocardial fibrosis. GLS and native T1 correlated with parameters of adverse LV remodelling, systolic and diastolic dysfunction and serum biomarkers of heart failure and myocardial injury. Conclusion. Our data highlight the role of myocardial fibrosis in adverse cardiac remodelling in AS. GLS has potential as a surrogate marker of myocardial fibrosis, and high native T1 and low GLS values differentiated patients with more advanced cardiac remodelling.

Technical Recommendations for Real-Time Echocardiography and Fluoroscopy Imaging Fusion in Catheter-Based Mitral Valve Paravalvular Leak and Other Procedures.

Widespread catheter-based interventions for structural heart disease have overtaken the treatment of paravalvular leaks (PVL). Multimodality imaging techniques play a crucial role in accurate diagnosis, procedure planning and performance. However, PVL closure is often technically challenging due to the complex anatomy of the defects and their relation to surrounding anatomical structures. The application of echocardiography and fluoroscopy imaging fusion (EFF) may simplify challenging imaginative three-dimensional reconstruction of the intracardiac anatomy and facilitate the procedure. To master new technology, personnel must make cognitive changes, overcome a learning curve, and obtain adequate theoretical knowledge. Main aim of this manuscript is to present basic recommendations for EFF application in practice, alongside, each scenario is supported by technically challenging clinical examples. We may conclude that our manuscript may provide useful information for physicians on EEF application in clinical practice.

Molecular Mechanisms behind Persistent Presence of Parvovirus B19 in Human Dilated Myocardium.

The role of parvovirus B19 (PVB19) in the pathogenesis of idiopathic dilated cardiomyopathy (DCM) remains poorly understood. Therefore, we have measured the levels of inflammation, fibrosis, apoptosis, and necrosis in endomyocardial biopsies (EMBs) and sera of nonischemic PVB19-positive (n = 14) and PVB19-negative (n = 18) DCM patients. Chronic persistence of PVB19 in myocardium did not induce significant infiltration of T cells (CD3 and CD45Ro) and macrophages (CD68), and did not secrete TNFα, IL-6, and CRB. The fibrosis in PVB19-positive EMBs was also lower compared to the virus-negative ones, while ECM degrading matrix metalloproteinase MMP1 and gelatinase MMP2 were significantly (by twofold) upregulated. In addition, there was no activation of neither apoptotic nor necrotic pathways. However, levels of antiapoptotic mitochondrial Bcl-2 and heat shock protein 60 (Hsp60) in PVB19-positive biopsies were almost threefold lower than in PVB19-negative ones revealing impairment of mitochondria. Altogether, data indicate that persistence of PVB19 in myocardiums of nonischemic DCM patients can cause myocardial ECM remodeling through the MMPs, such as MMP1 and MMP2, and mitochondrial impairment. The correlative analysis of measured biomarkers suggested likely further activation of apoptotic cell death pathways rather than fibrosis. Data also suggest that antiviral therapy could be beneficial for PVB19-positive DCM patients by managing further pathological myocardial remodeling.

Prevalence and prognostic relevance of myocardial inflammation and cardiotropic viruses in non-ischemic dilated cardiomyopathy.

BACKGROUND: Non-ischemic dilated cardiomyopathy (DCM) is a heterogeneous disease with a spectrum of etiological factors. However, subsets of the disease are not well-characterized with respect to these factors. The aim of this study was to evaluate the prevalence of myocardial inflammation and cardiotropic viruses in DCM patients and their impact on clinical outcome. METHODS: Fifty-seven patients with DCM underwent endomyocardial biopsy between 2010 and 2013. Biopsies were analyzed by polymerase chain reaction (PCR) for the presence of cardiotropic viruses, and inflammatory cell infiltration was assessed by immunohistochemistry. During a 5-year follow-up, 27 (47%) patients reached the composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death. RESULTS: Thirty-one (54%) patients had myocardial inflammation and cardiotropic viruses were detected in 29 (52%). The most frequent viruses were parvovirus B19 and human herpesvirus type-6. Four specific sub-groups were distinguished by PCR and immunohistochemistry: virus-positive (chronic) myocarditis, autoreactive inflammatory DCM, viral DCM, non-inflammatory DCM. The presence of a viral genome in myocardium or diagnosis of inflammatory DCM did not predict the outcome of composite outcome measures (p > 0.05). However, univariate Cox regression and survival function estimation revealed an association between inflammation by a high number of T-cells and poor prognosis. CONCLUSIONS: This study has shown that two markers - cardiotropic viruses and myocardial inflammation - are prevalent among DCM patients. They are also helpful in identifying sub-groups of DCM. An increased number of T-lymphocytes in the myocardium is a predictor of poor mid-term and long-term prognosis.

Midterm results of transventricular mitral valve repair: Single-center experience.

OBJECTIVE: The study objective was to evaluate the midterm outcomes of transventricular mitral valve repair and its association with the initial anatomy of the mitral valve. METHODS: This nonrandomized observational study included 88 patients (mean age, 60 years; 69% were men) who underwent transventricular mitral valve repair for severe degenerative mitral regurgitation between 2011 and 2017. Mitral valve function was assessed by echocardiography at 1 and 6 months and annually after the procedure. According to the location of mitral valve pathology, all patients were stratified into 4 anatomic types (A, B, C, and D). Results were assessed using Kaplan-Meier method, mixed-effects continuation ratio model, and multivariable Cox regression. RESULTS: Median follow-up of 42 months (interquartile range, 27-55) was complete for 83 patients (94.3%). There were 3 late deaths: 2 cardiac and 1 noncardiac. Recurrent mitral regurgitation greater than 2+ was observed in 29 patients (33%), and 18 patients (20.5%) underwent repeat surgery. Device success was 82% in type A at 6 months and thereafter; 87%, 85%, and 75% at 6, 12, and 36 months in type B, respectively; and 53% at 1 month and 20% at 24 months in type C. Probability of postoperative mitral regurgitation progression was higher in patients with greater preoperative left ventricular end-diastolic diameter, type B pathology, and type C pathology (P < .05). Risk factors of mitral regurgitation recurrence included increased left ventricle size (hazard ratio, 1.11; 95% confidence interval, 1.04-1.20; P = .001) and type C pathology (hazard ratio, 5.99; 95% confidence interval, 1.87-19.21; P = .003). CONCLUSIONS: Initial acceptable mitral regurgitation reduction after transventricular mitral valve repair of isolated P2 prolapse was possible but found durable in only 82% at 3 years. Higher risk of mitral regurgitation recurrence occurred with complex degenerative pathology.

Randomized Pilot Trial on Optimal Treatment Strategy, Myocardial Changes, and Prognosis of Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains an unresolved challenge. Many different diagnostic approaches are often required to diagnose, confirm, and evaluate MINOCA. The prevalence can be as high as 13% of all acute myocardial infarction patients, indicating that this condition is not rare. At this time, there have been no completed randomized clinical trials involving MINOCA patients, and a better understanding of the mechanisms and management of these patients is important. This exploratory analysis seeks to find possible etiologic factors, the value of novel biomarkers, and the effect of different treatment strategies in patients with MINOCA. METHODS: This prospective randomized pilot trial will include 150 patients with MINOCA. A thorough clinical, laboratory, and imaging evaluation will be performed, including novel biomarkers and modern imaging techniques (heart magnetic resonance imaging and noninvasive testing). The duration of the enrollment is 18 months, and duration of the follow-up is 12 months from the enrollment of the first patient. RESULTS: The trial is registered under www.clinicaltrials.gov: NCT04538924. The study is currently recruiting participants. CONCLUSIONS: Because MINOCA is not a benign disease, the results of the current investigation could inform future diagnostic and therapeutic strategies and enhance the understanding of MINOCA patients.

The use of near-infrared spectroscopy in the diagnosis of peripheral artery disease: A systematic review.

BACKGROUND: Peripheral arterial disease is a stenosis or occlusion of peripheral arteries that results in compromised blood flow and muscle ischemia. The available diagnostic methods are mostly used to measure and visualize blood flow and are not useful in the evaluation of perfusion, especially in diabetic patients, which is now considered to be a research priority by most of the vascular societies around the world as this is still a relatively poorly studied phenomenon. OBJECTIVE: The aim of this review is to explore the clinical significance of muscle tissue oxygenation monitoring in lower-extremity peripheral artery disease diagnosis using the near-infrared spectroscopy method. METHODS: A systematic search in PubMed, CINAHL, and Cochrane databases was performed to identify clinical near-infrared spectroscopy (NIRS) studies in English and Russian, published until September 2019, involving muscle tissue oxygenation in peripheral arterial disease (PAD). The manuscripts were reviewed by two researchers independently and scored on the quality of the research using MINORS criteria. RESULTS: After screening 443 manuscripts, 23 studies (n = 1580) were included. NIRS-evaluated recovery time seems to be more accurate than ankle-brachial index in diabetic patients to differentiate between moderate and severe claudication. Consistent findings across all the included studies showed that both the oxygenation and deoxygenation rates as well as the recovery times varied from patient to patient and therefore were not suitable for standardization. CONCLUSIONS: The clinical relevance of routine use of NIRS to diagnose PAD is unproven; therefore, its use is not currently part of standard-of-care for patients with PAD since the absolute values seem to vary significantly, depending on the outside conditions. More data need to be provided on the possible use of NIRS monitoring intraoperatively where the conditions can be more controlled.

Cardiomyogenic Differentiation Potential of Human Dilated Myocardium-Derived Mesenchymal Stem/Stromal Cells: The Impact of HDAC Inhibitor SAHA and Biomimetic Matrices.

Dilated cardiomyopathy (DCM) is the most common type of nonischemic cardiomyopathy characterized by left ventricular or biventricular dilation and impaired contraction leading to heart failure and even patients' death. Therefore, it is important to search for new cardiac tissue regenerating tools. Human mesenchymal stem/stromal cells (hmMSCs) were isolated from post-surgery healthy and DCM myocardial biopsies and their differentiation to the cardiomyogenic direction has been investigated in vitro. Dilated hmMSCs were slightly bigger in size, grew slower, but had almost the same levels of MSC-typical surface markers as healthy hmMSCs. Histone deacetylase (HDAC) activity in dilated hmMSCs was 1.5-fold higher than in healthy ones, which was suppressed by class I and II HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) showing activation of cardiomyogenic differentiation-related genes alpha-cardiac actin (ACTC1) and cardiac troponin T (TNNT2). Both types of hmMSCs cultivated on collagen I hydrogels with hyaluronic acid (HA) or 2-methacryloyloxyethyl phosphorylcholine (MPC) and exposed to SAHA significantly downregulated focal adhesion kinase (PTK2) and activated ACTC1 and TNNT2. Longitudinal cultivation of dilated hmMSC also upregulated alpha-cardiac actin. Thus, HDAC inhibitor SAHA, in combination with collagen I-based hydrogels, can tilt the dilated myocardium hmMSC toward cardiomyogenic direction in vitro with further possible therapeutic application in vivo.

Inflammation-Related Biomarkers Are Associated with Heart Failure Severity and Poor Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy.

Inflammation-related biomarkers are associated with clinical outcomes in mixed-etiology chronic heart failure populations. Inflammation-related markers tend to be higher in ischemic than in non-ischemic dilated cardiomyopathy (NI-DCM) patients, which might impact their prognostic performance in NI-DCM patients. Therefore, we aimed to assess the association of inflammation-related biomarkers with heart failure severity parameters and adverse cardiac events in a pure NI-DCM patient cohort. Fifty-seven patients with NI-DCM underwent endomyocardial biopsy. Biopsies were evaluated by immunohistochemistry for CD3+, CD45ro+, CD68+, CD4+, CD54+, and HLA-DR+ cells. Blood samples were tested for high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-α (TNF-α), soluble urokinase-type plasminogen activator receptor and adiponectin. During a five-year follow-up, twenty-seven patients experienced at least one composite adverse cardiac event: left ventricle assist device implantation, heart transplantation or death. Interleukin-6, TNF-α and adiponectin correlated with heart failure severity parameters. Patients with higher levels of interleukin-6, TNF-α, adiponectin or hs-CRP, or a higher number of CD3+ or CD45ro+ cells, had lower survival rates. Interleukin-6, adiponectin, and CD45ro+ cells were independently associated with poor clinical outcomes. All patients who had interleukin-6, TNF-α and adiponectin concentrations above the threshold experienced an adverse cardiac event. Therefore, a combination of these cytokines can identify high-risk NI-DCM patients.

Left ventricular global longitudinal strain predicts elevated cardiac pressures and poor clinical outcomes in patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Risk stratification in patients with non-ischemic dilated cardiomyopathy (NI-DCM) is essential to treatment planning. Global longitudinal strain (GLS) predicts poor prognosis in various cardiac diseases, but it has not been evaluated in a cohort of exclusively NI-DCM. Although deformation parameters have been shown to reflect diastolic function, their association with other hemodynamic parameters needs further elucidation. We aimed to evaluate the association between GLS and E/GLS and invasive hemodynamic parameters and assess the prognostic value of GLS and E/GLS in a prospective well-defined pure NI-DCM cohort. METHODS AND RESULTS: Forty-one patients with NI-DCM were enrolled in the study. They underwent a standard diagnostic workup, including transthoracic echocardiography and right heart catheterization. During a five-year follow-up, 20 (49%) patients reached the composite outcome measure: LV assist device implantation, heart transplantation, or cardiovascular death. Pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure, pulmonary vascular resistance (PVR) correlated with GLS and E/GLS (p < 0.05). ROC analysis revealed that GLS and E/GLS could identify elevated PCWP (≥ 15 mmHg) and PVR (> 3 Wood units). Survival analysis showed GLS and E/GLS to be associated with short- and long-term adverse cardiac events (p < 0.05). GLS values above thresholds of -5.34% and -5.96% indicated 18- and 12-fold higher risk of poor clinical outcomes at one and five years, respectively. Multivariate Cox regression analysis revealed that GLS is an independent long-term outcome predictor. CONCLUSION: GLS and E/GLS correlate with invasive hemodynamics parameters and identify patients with elevated PCWP and high PVR. GLS and E/GLS predict short- and long-term adverse cardiac events in patients with NI-DCM. Worsening GLS is associated with incremental risk of long-term adverse cardiac events and might be used to identify high-risk patients.

First in human experience with an epicardial beating heart device for secondary mitral regurgitation.

OBJECTIVE: We describe a novel, off-pump, epicardial implant that is intended to reshape both the mitral valve annulus and the left ventricle (LV) in those with secondary mitral regurgitation (MR). METHODS: Five patients underwent an epicardial implant with the Mitral Touch device (Mitre Medical Corp, Morgan Hill, Calif), during concomitant off-pump coronary artery bypass for secondary MR. The median age was 71.2 years; 4 patients had severe MR and 1 moderate. Patients were followed for 1 year with transthoracic echocardiography and computed tomography. Safety, cardiac remodeling, and MR were assessed by an independent core laboratory. RESULTS: One patient died within 30 days from nondevice-related organ failure and the remaining 4 survived through 1-year follow-up. Implant technical success was 100% and took an average of 52 minutes. Paired computed tomography showed mean left ventricular end-systolic volume remodeling at 1 and 12 months of -35% and -31%, respectively. They averaged left atrial end-systolic volume remodeling of -12% and -15% at 1 and 12 months. Right ventricular end-systolic volume changes of -19% and -8% and right atrial end-systolic volume remodeling of -5% and 1%, at the 1- and 12-month time points were noted. Regurgitant volume by transthoracic echocardiography decreased by 46% and 44% and the ejection fraction from 34.6% to 32.1% and 39.5%, at 1 and 12 months, respectively. There were no device-related complications reported to 1 year. CONCLUSIONS: The Epicardial Mitral Touch System for Mitral Regurgitation (ENRAPT-MR) study demonstrates a first-in-man, off-pump, epicardial repair of secondary MR. Procedural safety and geometric correction of the mitral valve apparatus and LV was achieved. Further studies in the United States are underway.

Rescue transventricular off-pump mitral valve repair with artificial neochords for acute mitral regurgitation due to postinfarction papillary muscle rupture.

BACKGROUND: We report 3 cases of rescue transventricular off-pump mitral valve (MV) repair in high-risk patients with acute mitral regurgitation (MR) due to post-myocardial infarction (MI) papillary muscle rupture (PMR). METHODS: The 3 patients presented with acute inferior ST elevation myocardial infarction, cardiogenic shock, and pulmonary edema. Their preoperative peak troponin I levels were 1909 ng/L, 16,963 ng/L, and 8299 ng/L. All 3 patients underwent successful percutaneous intervention to the culprit coronary artery, and antiplatelet therapy was initiated. All patients required inotropic support and had an intra-aortic balloon pump inserted preoperatively. Transesophageal echocardiography (TEE) demonstrated severe eccentric MR due to the leaflet prolapse secondary to PMR. The patients' estimated EuroSCORE II scores were 16.03%, 16.68%, and 7.81%, and their Society of Thoracic Surgeons scores were 14.77%, 18.24%, and 9.8%, respectively. All 3 patients underwent urgent transventricular off-pump MV repair using artificial chords, with 2 or 3 three neochords implanted. The duration of operation was <2 hours, and intraoperative and postoperative drainage was minimal in all cases. MV function was assessed by qualitative and semiquantitative TEE. RESULTS: Intraoperative MR reduction to a mild level was achieved in all 3 patients. All patients had moderate MR at discharge, likely due to left ventricular remodeling. Severe MR recurred in all patients, at 5, 4, and 2 months of follow-up, respectively. All 3 patients underwent an elective MV reoperation via conventional approach. CONCLUSIONS: Off-pump transventricular MV repair may offer a safe and feasible alternative to stabilize high-risk patients with acute MR due to post-MI PMR. Although early MR recurrence is concerning, urgent transventricular MV repair may serve as a bridge to conventional surgery in such unstable patients.

Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Improves Energetic Status and Cardiomyogenic Differentiation of Human Dilated Myocardium-Derived Primary Mesenchymal Cells.

BACKGROUND: In this study the effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) on the energetic status and cardiomyogenic differentiation of human healthy and dilated myocardium-derived mesenchymal stromal cells (hmMSC) have been investigated. METHODS: The hmMSC were isolated from the healthy and dilated post-operation heart biopsies by explant outgrowth method. Cell proliferation, HDAC activity, mitochondrial membrane potential, and level of adenosine triphosphate (ATP) were evaluated. The effect of SAHA on mitochondrial parameters has been investigated also by Seahorse XF analyzer and cardiomyogenic differentiation was confirmed by the expression of transcription factor NK2 Homeobox 5 (Nkx2.5), cardiac troponin T and alpha cardiac actin at gene and protein levels. RESULTS: Dilated myocardium-derived hmMSC had almost 1.5 folds higher HDAC activity compared to the healthy cells and significantly lower mitochondrial membrane potential and ATP level. HDAC class I and II inhibitor SAHA improved energetic status of mitochondria in dilated myocardium-isolated hmMSC and increased expression of cardiac specific proteins during 14 days of exposure of cells to SAHA. CONCLUSIONS: HDAC inhibitor SAHA can be a promising therapeutic for dilated cardiomyopathy (DCM). Dilated hmMSC exposed to SAHA improved energetic status and, subsequently, cardiomyogenic differentiation. Data suggest that human dilated myocardium-derived MSC still have cardio tissue regenerative potential, which might be stimulated by HDAC inhibitors.