Significant Improvement In Ejection Fraction Research Articles

The Safety and Efficacy of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Patients With Heart Failure and Myocardial Infarction: A Meta-Analysis of Clinical Trials.

Evidence from preclinical and clinical studies suggests that human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) may be useful in treating heart failure and acute myocardial infarction (MI). However, the effects of stem cell therapy on patients with heart failure remain the subject of ongoing controversy, and the safety and effectiveness of HUC-MSCs therapy have not yet been proven. To date, there has been no systematic overview and meta-analysis of clinical studies using HUC-MSCs therapy for heart failure and MI. The purpose of this study is to assess the safety and efficacy of HUC-MSC therapy versus a placebo in patients with heart failure and MI. While preparing this systematic review and meta-analysis, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer literature search of PubMed was performed. We considered randomized controlled trials (RCTs) that reported data on the safety and efficacy of HUC-MSC transplantation in patients with heart failure and MI. Two investigators independently searched the literature, extracted data, and rated the quality of the included research. Pooled data were analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was ejection fraction (EF), whereas the secondary outcomes were readmission and mortality rates. Three RCTs (201 patients) were included in this meta-analysis. The overall effect did not favor either of the two groups in terms of risk of readmission (risk ratio = 0.5, 95% confidence interval (CI) = 0.22-1.15, p = 0.10) as well as mortality rate (risk ratio = 0.44, 95% CI = 0.14-1.44, p = 0.18). However, there was an improvement in EF in patients who received HUC-MSCs compared to placebo after 12 months of transplantation (mean difference (MD) = 3.21, 95% CI = 2.91-3.51, p < 0.00001). At the six-month follow-up period, there was no significant improvement in EF (MD = 1.30, 95% CI = -1.94-4.54), p = 0.43), indicating that the duration of follow-up can shape the response to therapy. Our findings indicate that HUC-MSC transplantation can improve EF but has no meaningful effect on readmission or mortality rates. Existing evidence is insufficient to confirm the efficacy of HUC-MSCs for broader therapeutic applications. Therefore, additional double-blind RCTs with larger sample sizes are required.

Treatment of ischemic heart failure through ultrasound-targeted microbubble destruction and it's mechanism

Abstract Background The cavitation effect mediated by ultrasonic-targeted microbubble destruction (UTMD) can regulate the microenvironment and circulation of ischemic myocardium. The UTMD cavitation effect can rapidly enhance blood perfusion and improve cardiac function in patients with ischemic heart failure. However, the internal mechanism of this treatment has yet to be reported. Objective The objective of this study was to explore the underlying mechanism of UTMD-mediated cavitation effect to rapidly improve cardiac function in rats with ischemic heart failure. Methods In the first part of the study, the ischemic heart failure model was induced by ligation of the left anterior descending branch coronary in Sprague-Dawley rats, the rats were randomly divided into 7 groups: sham group, HF group, HF+MB(microbubble) group, HF+US(ultrasound) group, HF+UTMD group, HF+UTMD+LY294002(PI3K inhibitor) group, and HF+LY294002 group. Serum BNP level and echocardiographic parameters were measured to evaluate cardiac function. Thereafter, SD rats were treated with UTMD by specific ultrasonic parameters and microbubble concentration, cardiac function should be reassessed after treatment. Finally, the myocardial tissues were extracted for Western Blot and immunohistochemical analysis to detect the protein expression of the PI3K/Akt/eNOS signaling pathway, and the contents of serum nitric oxide(NO) and myocardial ATP were detected by Elisa. Results The application of UTMD resulted in significant improvements in ejection fraction (EF) and fractional shortening (FS) in rats with ischemic heart failure, as compared to the HF group (EF: 37.16 ± 1.21% vs. HF+UTMD: 46.31 ± 3.00%, P=0.0057; FS: 18.53 ± 0.58% vs. HF+UTMD: 24.05 ± 1.84%, P=0.0089). Additionally, UTMD treatment led to the activation of the PI3K/Akt/eNOS signaling pathway (HF vs. HF+UTMD, P &amp;lt; 0.01), and promoted the production of NO and ATP (HF vs. HF+UTMD, both, P&amp;lt; 0.05). However, when a PI3K inhibitor was used, the cardiac protective effects of UTMD treatment were largely eliminated. EF and FS deteriorated significantly (EF: HF+UTMD+LY294002: 42.84±2.88% vs. HF+LY294002: 32.73±3.05%, P&amp;lt;0.0001; FS: HF+UTMD+LY294002: 21.94±1.69% vs. HF+LY294002: 16.36±1.76%, P&amp;lt;0.0001), and the production of NO and ATP decreased significantly (HF+UTMD+LY294002 vs. HF+LY294002, both, P&amp;lt; 0.05). Conclusion The UTMD-mediated cavitation effect can rapidly improve the cardiac function of ischemic heart failure rats by activating PI3K/Akt/eNOS signaling pathway and promoting the release of NO and ATP.

Abstract P3071: Targeting Neutrophil Sting And Type I Interferon Activation In Myocardial Ischemia-Reperfusion Injury

Introduction: Inflammation following myocardial ischemia/reperfusion (MI/R) plays a significant role in damaging cardiomyocytes and influencing infarct size, with neutrophils being the most rapid and numerous cells in the post-MI/R heart at 24 hours post reperfusion. Preliminary single-cell RNA sequencing data shows type I interferon (IFN) responding neutrophils are present in the hearts of mice 24 hours post-MI/R. The following study aims to address how the type I IFN responding neutrophil phenotype identified in single-cell RNA sequencing data affects cardiac inflammation in MI/R. We hypothesize that STING and type I IFN activation in neutrophils in the early stages of inflammation can exacerbate inflammation, causing further damage to the heart in MI/R. Methods: Male C57BL/6J mice (10-11 weeks old) underwent 60 minutes of ischemia followed by reperfusion, and were dosed with either vehicle, a STING inhibitor (H151), or an IFNAR1 antibody (ab) at reperfusion and at 24 hours following reperfusion. Cardiac function was assessed two weeks post-reperfusion via echocardiography and tissue samples were collected for histological analysis. Results: Mice treated with IFNAR1 ab showed significant improvement in ejection fraction (44.9% ± 6.8) compared to mice treated with vehicle (31.9% ± 6.2; One-way ANOVA, N=5-6, p&lt;0.05). Additionally, mice treated with IFNAR1 ab showed significant improvements in left ventricular end systolic volume (LVESD) (3.16mm ± 0.52) compared to vehicle treated mice (3.89mm ± 0.40; One-way ANOVA, N=5-6, p&lt;0.05). Mice treated with H151 showed significant improvement in ejection fraction (43.8% ± 7.1) compared to mice treated with vehicle (31.9% ± 6.2; One-way ANOVA, N=5-6, p&lt;0.05). Treatment with H151 or IFNAR1 ab reduced scar size (7.22% ± 3.6; 7.88% ± 3.1%) compared to mice treated with vehicle (9.74% ± 3.7; N=5-6). Conclusion: These data show that targeting the early IFN response in MI/R can improve cardiac function, and provide a basis for studies identifying the effects of the neutrophil specific STING and type I IFN activation following MI/R. If correct, this pathway could be a powerful and clinically feasible point of intervention to improve cardiac recovery after MI/R.

Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia.

Friedreich's ataxia (FA) is a life-threatening autosomal recessive disorder characterized by neurological and cardiac dysfunction. Arrhythmias and heart failure are the main cause of premature death. From prior studies in murine models of FA, adeno-associated virus encoding the normal human frataxin gene (AAVrh.10hFXN) effectively treated the cardiac manifestations of the disease. However, the therapeutic dose window is limited by high level of human frataxin (hFXN) gene expression associated with toxicity. As a therapeutic goal, since FA heterozygotes have no clinical manifestations of FA, we estimated the level of frataxin (FXN) necessary to convert the heart of a homozygote to that of a heterozygote. In noncardiac cells, FA heterozygotes have 30-80% of normal FXN levels (17.7-47.2 ng/mg, average 32.5 ng/mg) and FA homozygotes 2-30% normal levels (1.2-17.7 ng/mg, average 9.4 ng/mg). Therefore, an AAV vector would need to augment endogenous in an FA homozygote by >8.3 ng/mg. To determine the required dose of AAVrh.10hFXN, we administered 1.8 × 1011, 5.7 × 1011, or 1.8 × 1012 gc/kg of AAVrh.10hFXN intravenously (IV) to muscle creatine kinase (mck)-Cre conditional knockout Fxn mice, a cardiac and skeletal FXN knockout model. The minimally effective dose was 5.7 × 1011 gc/kg, resulting in cardiac hFXN levels of 6.1 ± 4.2 ng/mg and a mild (p < 0.01 compared with phosphate-buffered saline controls) improvement in mortality. A dose of 1.8 × 1012 gc/kg resulted in cardiac hFXN levels of 33.7 ± 6.4 ng/mg, a significant improvement in ejection fraction and fractional shortening (p < 0.05, both comparisons) and a 21.5% improvement in mortality (p < 0.001). To determine if the significantly effective dose of 1.8 × 1012 gc/kg could achieve human FA heterozygote levels in a large animal, this dose was administered IV to nonhuman primates. After 12 weeks, the vector-expressed FXN in the heart was 17.8 ± 4.9 ng/mg, comparable to the target human levels. These data identify both minimally and significantly effective therapeutic doses that are clinically relevant for the treatment of the cardiac manifestations of FA.

P176 GLOBAL LONGITUDINAL STRAIN AS A PREDICTOR OF RESPONSE TO CARDIAC CONTRACTILITY MODULATION IN PATIENTS WITH HEART FAILURE: A CASE SERIES

Abstract Background Cardiac contractility modulation (CCM) in heart failure (HF) patients with reduced ejection fraction (HFrEF) is an innovative therapy which may contribute to increased exercise capacity and quality of life and reduced hospitalizations. With speckle–tracking echocardiography and global longitudinal strain (GLS), changes in myocardial function can be detected with greater sensitivity than conventional approaches for measuring diastolic and systolic function, including left ventricular ejection fraction. We aim to analyze the usefulness of GLS in detecting improvement in systolic function and response to CCM treatment. Methods We studied 5 patients with CCM referred to our outpatient cardiology clinic. All patients underwent complete echocardiography with evaluation of GLS and ejection fraction. Follow–ups were performed at 1, 3, and 6 months. Results All patients were men (mean age 65.3±15.7 yrs). Mean baseline ejection fraction was 37.1±9.3%, mean GLS was 7.7±3.1%, and patients had mild–to–moderate left ventricular enlargement (mean indexed telediastolic volumes 101.4±8.7 ml/m2). Follow–up performed at the first month showed values similar to baseline values. Between the third and sixth months, a non–significant improvement in ejection fraction and GLS was recorded (EF 40.75±9.6% p=0.51; GLS 8.9±4.2 p=0.62). Indexed telediastolic volumes were reduced (101.4±9.3 ml/m2 vs 89.5±7.4 ml/m2 p=0.05). Conclusions CCM therapy seems to be useful in achieving volumetric remodeling in patients with HFrEF. GLS assessment may be useful in detecting improvement in systolic function. Further studies with larger samples and longer follow–up are needed to confirm these results.

PO-02-009 LEAD REVISION AND OPTIMIZATION OF CRT NONRESPONDERS USING ELECTRICAL DYSSYNCHRONY MAPPING

Identification and treatment of CRT nonresponders who have poor LV lead position is a significant clinical problem. To describe how a new technology for measuring electrical dyssynchrony can be used to identify CRT patients with poor LV lead position and optimize their device programming with or without LV lead revision. An ECG system of 9 anterior/9 posterior leads was used to quantify a novel measure of electrical dyssynchrony called cardiac resynchronization index (CRI), defined as % change in area under the curve between all combinations of anterior and posterior electrodes as compared to native (CRT off). An electrical dyssynchrony map (EDM) was used to graphically display CRI values at multiple different atrial-ventricular delays (AVD) and ventricular-ventricular delays (VVD). Poor LV lead position was defined as optimal CRI (CRIopt) < 90% or need for VVD > -80 ms (LV ahead) to achieve CRIopt. We studied 19 CRT nonresponder patients with poor LV lead position based on EDM criteria. Mean CRI was 31.8±21.5%. LV lead location was anterior (n=8), apical (n=6) and posterior/lateral (n=5). Figure 1 shows an EDM of a patient before and after lead revision. Initial lead was an anterior epicardial lead. CRIopt was at VVD of -90 ms (LV-paced ahead) and EF did not improve with optimization. After placement of a lateral LV lead, VVD optimization of -30 ms resulted in an improvement in EF from 25% to 33%. Fifteen patients were programmed to CRIopt. Four patients were optimized to LV-only pacing at the optimal AVD and 11 were programmed biventricular with mean VVD -61±25 ms (LV-paced ahead). Five of these patients had minimal or no improvement with optimization. and underwent lead revision. Four patients did not have a device setting with a substantially improved CRI and 2 of 4 underwent LV lead revision. All 7 patients with LV lead revision had repeat optimization after lead revision. LV ejection fraction (EF) measured 4-6 months post-optimization improved significantly (p ≤ 0.05) from 29.1 ± 7.1% to 33.5 ± 5.8% in the 17 patients optimized by reprogramming and/or lead revision. EDM is a noninvasive, practical methodology that can be used to identify CRT nonresponder patients with poor LV lead position, determine whether lead revision may be of benefit, and optimize device programming before and/or after lead revision. This clinical approach results in a significant improvement in EF of 4.4%.

Heart Failure and Myocarditis in a 27-Year-Old Male with Human Immunodeficiency Virus

HIV-associated cardiomyopathy is a complication of HIV infection that affects the structure and function of the heart. Early detection and diagnosis is crucial and routine cardiac workup is recommended with people living with HIV. In this report, we have a 27-year-old, Male, who identifies as gay, with a history of AIDS and has been living with HIV since 5 years from admission with a recent undetectable viral load. He presented with undocumented fever, cough and dyspnea over 7 days nonresponsive to Azithromycin. Multimodality imaging stands in the forefront of diagnosis of HIV-associated Cardiomyopathy and cardiomyopathies in general. Transthoracic 2D echocardiography or Cardiac MRI is recommended on initial evaluation among patients suspected to have the disease in order to identify its specific phenotype. Echocardiography is further recommended in monitoring the progression of the disease and response to therapy. Patient’s initial echocardiogram fulfilled the criteria for DCM with an LVEDD of 59mm and a reduced ejection fraction of 40%. Due to scheduling issues, Cardiac MRI was done 77 days after guideline-directed medical therapy for heart failure with reduced ejection fraction ARNI, beta-blockers, SGLT-2 inhibitors, and diuretics as needed. Results showed significant improvement in ejection fraction to 60%, with resolution of previously seen hypokinesia, but persistence of the LV dilatation with an LV volume index of 121 mL/m2. More importantly, post-contrast imaging on the short axis show that there are linear mid-wall enhancement indicative of non-ischemic patterns of enhancement involving the basal to mid anterior septum, basal to mid inferior septum, basal to mid inferolateral, and basal lateral segments characteristic of a post-myocarditis cause of dilated cardiomyopathy.

Effects of angiotensin receptor-neprilysin inhibitors (ARNIs) on the glucose and fat metabolism biomarkers leptin and fructosamin

Abstract Background Heart Failure with reduced ejection fraction (HFrEF) has a life time risk about 20% among adults aged 40 years or older and a 5-year mortality rate about 60% [1,2]. However novel therapies have shown to improve this outcome. One novel agent are angiotensin receptor-neprilysin inhibitors (ARNIs) that increase the BNP levels via inhibiting neprilsyin [3]. This has beneficial effects on heart failure by reducing preload, inflammation and fibrosis. Neprilysin also interacts with leptin and is known to correlate with the incidence and progression of heart failure if chronically elevated [4]. Furthermore beneficial affects of ARNI therapy on glucose metabolism were reported in a post-hoc analysis of the PARADIGM-HF trial [5]. In this study we aim to investigate the effect of ARNI therapy on the fat metabolism markers leptin and on the glucose metabolism marker fructosamin. Methods In total, we included 74 patients with HFrEF with ischemic (N=37) and non-ischemic (n=37) origin in the present study. The mean NYHA class was II–III, the mean BMI 28 (SD 6.3). Patients had well established heart failure therapy before starting ARNI therapy with sacubitril/valsartan. 88% of patients were on ACE-inhibitors, 86% on beta blockers and 68% on mineralocorticoid receptor antagonists. Serum samples were obtained and analyzed for leptin, fructosamin and pBNP before and 3–6 month after ARNI therapy. The clinical parameters LVEF and NYHA class were assessed before and 3–6 month after ARNI therapy. Results Baseline leptin level was 15.0 (SD 17.2), baseline fructosamin level was 370.1 (SD 167.7) and baseline pBNP level was 1494.9 (SD 1281.4). Under therapy a significant improvement of ejection fraction from 29,8% to 37,5% (7,7 SD 8,5 P≤0.001), an improvement of NYHA stadium from 2.46 (SD 0.62) to 1.96 (SD 0.63, p=0.005) and a significant decrease of pBNP (562.1 SD 1256.4, p=0.018) was found. Along with that, a significant increase in leptin levels (3.6 SD 8.85, p=0.012) and a significant increase in fructosamine levels (93.5 SD 160.6, p=0.013) was shown. Conclusion Under therapy with ARNI we showed a sufficient therapy response with improvement of ejection fraction and decrease of pBNP in line with literature. Surprisingly metabolism biomarkers did significantly worsen under the first three to six month after new ARNI therapy. To distinguish between a side effect of ARNI therapy or consequence of heart failure itself further investigations are needed. Funding Acknowledgement Type of funding sources: None.

The role of a multidisciplinary heart failure clinic in optimization of guideline-directed medical therapy: HF-optimize

BackgroundGuideline-directed medical therapy (GDMT) reduces mortality and hospitalizations in adults with heart failure with reduced ejection fraction (HFrEF); however, few are receiving GDMT. National registries show as few as 1% of patients are receiving appropriate GDMT. Development of heart failure clinics achieving optimal GDMT are crucial to improve outcomes for HFrEF patients. ObjectiveWe developed a multidisciplinary HF-Optimize clinic aimed at improving GDMT use along with providing education, resources, and comorbidity screening for adults with HFrEF. MethodsWe targeted patients with newly diagnosed HFrEF and/or recent or multiple admissions for 6 visits over 12 weeks. We measured medication use, ejection fraction, 6-minute walk test distance, and health-related quality of life (EuroQol Visual Analog Scale) at visits 1 and 6. ResultsOne-hundred ten patients completed all visits. Patients were a mean age of 58 (±14) years, 37% were female, and 42% were of non-White race. From visit 1 to visit 6, utilization of GDMT increased from 35.5% to 85.5% (p < 0.001) and significant improvements in ejection fraction (25.9% to 35.5%, p < 0.001), 6-minute walk distance (1032 feet to 1121.7 feet, p = 0.001), and quality of life (63.8/100 vs 70.8/100, p = 0.002). Only 2 patients (1.8%) that completed HF-Optimize had a 30-day heart failure readmission. ConclusionOur multidisciplinary HF-Optimize clinic improved medication usage and clinical outcomes. Further studies are needed to validate outcomes of multidisciplinary GDMT clinics.

Midterm Outcome of Hybrid Transcatheter and Minimally Invasive Left Ventricular Reconstruction for the Treatment of Ischemic Heart Failure

BackgroundLeft ventricular (LV) remodeling after anterior myocardial infarction (AMI) can cause a pathological increase in LV volume, reduction in LV ejection fraction (EF), and symptomatic heart failure (HF). This study evaluates the midterm results of a hybrid transcatheter and minimally invasive surgical technique to reconstruct the negatively remodeled LV by myocardial scar plication and exclusion with microanchoring technology. MethodsRetrospective single-center analysis of patients who underwent hybrid LV reconstruction (LVR) with the Revivent TransCatheter System. Patients were accepted for the procedure when they presented with symptomatic HF (New York Heart Association class ≥ II, EF < 40%) after AMI, in the presence of a dilated LV with either akinetic or dyskinetic scar in the anteroseptal wall and/or apex of ≥50% transmurality. ResultsBetween October 2016 and November 2021, 30 consecutive patients were operated. Procedural success was 100%. Comparing echocardiographic data preoperatively and directly postoperatively, LVEF increased from 33 ± 8% to 44 ± 10% (p < 0.0001). LV end-systolic volume index decreased from 58 ± 24 mL/m2 to 34 ± 19 mL/m2 (p < 0.0001) and LV end-diastolic volume index decreased from 84 ± 32 mL/m2 to 58 ± 25 mL/m2 (p < 0.0001). Hospital mortality was 0%. After a mean follow-up of 3.4 ± 1.3 years, there was a significant improvement of New York Heart Association class (p = 0.001) with 76% of surviving patients in class I-II. ConclusionsHybrid LVR for symptomatic HF after AMI is safe and results in significant improvement in EF, reduction in LV volumes, and sustained improvement in symptoms.

Cardiac resynchronization therapy response in cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is a nonischemic cardiomyopathy (NICM) characterized by infiltration of noncaseating granulomas involving the heart with highly variable clinical manifestations that can include conduction abnormalities and systolic heart failure. Cardiac resynchronization therapy (CRT) has shown significant promise in NICM, though little is known about its efficacy in patients with CS. To determine if CRT improved cardiac remodeling in patients with CS. We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent CRT implantation at the Mayo Clinic enterprise from 2000 to 2021. Baseline characteristics, imaging parameters, heart failure hospitalizations and need for advanced therapies, and major adverse cardiac events (MACE) were assessed. Our cohort was comprised of 55 patients with 61.8% male and a mean age of 58.7 ± 10.9 years. Eighteen (32.7%) patients had definite CS, 21 (38.2%) had probable CS, while 16 (29.1%) had presumed CS, and 26 (47.3%) with extracardiac sarcoidosis. The majority underwent CRT-D implantation (n = 52, 94.5%) and 3 (5.5%) underwent CRT-P implantation with 67.3% of implanted devices being upgrades from prior pacemakers or implantable cardioverter defibrillators. At 6 months postimplantation there was no significant improvement in ejection fraction (34.8 ± 10.9% vs. 37.7 ± 14.2%, p = .331) or left ventricular end-diastolic diameter (58.5 ± 10.2 vs. 57.5 ± 8.1 mm, p = .236), though mild improvement in left ventricular end systolic diameter (49.1 ± 9.9 vs. 45.7± 9.9 mm, p < .0001). Within the first 6 months postimplantation, 5 (9.1%) patients sustained a heart failure hospitalization. At a mean follow-up of 4.1± 3.7 years, 14 (25.5%) patients experienced a heart failure hospitalization, 11 (20.0%) underwent cardiac transplantation, 1 (1.8%) underwent left ventricular assist device implantation and 7 (12.7%) patients died. Our findings suggest variable response to CRT in patients with CS with no overall improvement in ventricular function within 6 months and a substantial proportion of patients progressing to advanced heart failure therapies.

Impact of exercise training on myocardial contractile functions assessed by cardiac magnetic resonance in post-myocardial infarction patients

BackgroundImprovement of functional capacity and mortality reduction in post-MI patients were found to be associated with regular exercise training. The cardiac magnetic resonance (CMR) is considered the most accurate non-invasive modality in quantitative assessment of left ventricular (LV) volumes and systolic functions. Our main objective was to investigate the impact of exercise training on LV systolic functions in patients post anterior MI using CMR. 32 patients on recommended medical treatment 4 week after having a successful primary PCI for an anterior MI were recruited, between May 2018 and May 2019. They were divided into two groups, training group (TG): 16 assigned to a 12 week exercise training program and control group (CG): 16 who received medical treatment without participating in the exercise training program. Treadmill exercise using modified Bruce protocol was done to TG before and after the training program in order to record the resting and maximum HR, metabolic equivalent (MET), and calculate HR reserve. CMR was performed for all patients 4 weeks after PCI and was repeated after completion of the study period to calculate ejection fraction (EF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and wall motion score index (WMSI).Results100% were males. 6 patients from CG dropped during follow-up, no statistically significant difference between the two groups regarding age, BMI, smoking status, hypertension, diabetes mellitus and dyslipidemia. Using the CMR, the TG showed significant improvement in EF (36.6 ± 14.2% to 43.1 ± 12.4%; P < 0.001) and WMSI (2.03 ± 0.57 to 1.7 ± 0.49; P < 0.001), without statistically significant change in LV volumes. Regarding CG no significant changes in EF, WMSI, LV volumes were found. There was significant improvement in EF and WMSI change before and after study in TG vs. CG [6.5 (2.3–9.0) vs. − 2.0 (− 6.8 to 1.3), P value < 0.001] and [− 0.3 (− 0.5 to 0.1) vs. 0.1 (− 0.1 to − 0.5), P value 0.001] respectively.Conclusions12 weeks of exercise training program in post-MI patients have a favorable impact on LV global and regional systolic functions without adversely affecting LV remodeling (as assessed by CMR).

Comparing the effect of bone marrow mono-nuclear cells with mesenchymal stem cells after acute myocardial infarction on improvement of left ventricular function: a meta-analysis of clinical trials

BackgroundThe effect of transplantation of bone-marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs) on ejection fraction (LVEF) has been studied in patients with acute myocardial infarction (AMI) in clinical trials. This raises the question that which type of cell may help improve LVEF better in AMI patients. No meta-analysis of clinical trials has yet addressed this question.MethodsElectronic databases were searched thoroughly to find eligible trials on the effects of transplantation of BM-MNCs and MSCs in patients with AMI. The primary outcome was improvement in LVEF. Data were synthesized using random-effects meta-analysis. For maximizing the credibility of subgroup analysis, we used the instrument for assessing the Credibility of Effect Modification of Analyses (ICEMAN) for meta-analyses.ResultsA total of 36 trials (26 on BM-MNCs and 10 on MSCs) with 2489 patients (1466 were transplanted [1241 with BM-MNCs and 225 with MSCs] and 1023 as controls) were included. Both types of cells showed significant improvements in ejection fraction in short-term follow-up (BM-MNCs: WMD = 2.13%, 95% CI = 1.23 to 3.04, p < 0.001; MSCs: WMD = 3.71%, 95% CI = 2.32 to 5.09, p < 0.001), and according to ICEMAN criteria, MSCs are more effective. For selected population of patients who received stem cell transplantation in early course after AMI (less than 11 days), this effect was even more pronounced (BM-MNC: WMD = 3.07%, 95% CI = 1.97 to 4.17, p < 0.001, I2 = 40.7%; MSCs: WMD = 5.65%, 95% CI = 3.47 to 7.84, p < 0.001, I2 = 84.6%).ConclusionOur results showed that transplantation of MSCs after AMI might increase LVEF more than BM-MNCs; also, based on ICEMAN, there was likely effect modification between subgroups although uncertainty still remained.

Non-invasive hemodynamic evaluation following TAVI for severe aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: None. Background Various hemodynamic changes occur following Transcatheter aortic valve implantation (TAVI) that impact treatment decisions. NICaS, a noninvasive whole-body bio-impedance monitoring system to assess hemodynamics and fluid balance, was tested in patients with severe aortic stenosis (AS) before and after TAVI. Methods Between October 2019 and December 2020 all consecutive patients with severe AS undergoing TAVI were assessed by NICaS at several time points – 24 hours before (baseline) and after the procedure, at hospital discharge and at 30 days to 1 year follow-up. Excluded were patients undergoing TAVI due to reasons other than severe AS, patients under general anesthesia and those who died at the catheterization lab or immediately following the procedure. Results We performed hemodynamic analysis on 97 consecutive patients who underwent TAVI using either Medtronic Evolut R (54%), Edwards Sapien 3 (32%) or SYMETIS ACURATE neo (13%). Patients were more often women (54%) and had multiple comorbidities including hypertension (83%), dyslipidemia (79%), coronary artery disease (46%), and diabetes mellitus (37%). Compared to baseline NICaS measurements, we observed increases in systolic blood pressure (BP) and total peripheral resistance (TPR) within 24 hours following TAVI (systolic BP 132.5±22.3 mmHg at baseline versus 148.4±23.9 mmHg after TAVI, P&amp;lt;0.001; TPR 1754±520 versus 2094±752 dynes*s/cm5, respectively, P&amp;lt;0.001) while cardiac output (CO), cardiac index (CI) and stroke volume (SV) decreased (CO 4.2±1.2 versus 3.9±1.2 L/min, respectively, P=0.013; SV 62±15 versus 56±15.8 mL, P=0.002). However, opposite trends were demonstrated exclusively in patients with ejection fraction (EF) under 40%. At follow-up (median 59 days, IQR [39.5-91]) these hemodynamic measurements returned to values that were not statistically different from the baseline, despite a significant improvement in EF from baseline to follow-up (55.6±11.6 to 59.4±9.4%, P&amp;lt;0.001). Conclusion A unique pattern of short and longer term adaptive hemodynamic changes was demonstrated using the NICaS system among patients undergoing TAVI. These findings require validation and further research to their underlying mechanism if NICaS is to be used as a bedside monitoring tool to guide treatment decisions.

Five-Year Outcome of Hybrid Transcatheter and Minimally Invasive Left Ventricular Reconstruction for the Treatment of Ischemic Heart Failure

<h3>Purpose</h3> Remodelling of the left ventricle (LV) after anterior myocardial infarction (AMI) can result in a pathological increase in LV volume, reduction in LV ejection fraction (EF) and symptomatic heart failure (HF). We describe the five-year results of a hybrid transcatheter and minimally invasive surgical technique to reconstruct the remodelled LV by myocardial scar plication and exclusion. <h3>Methods</h3> Patients were eligible for the procedure when they presented with symptomatic HF (NYHA-class ≥II, EF<40%) after AMI. All patients had a dilated LV with a- or dyskinetic scar in the anteroseptal wall and/or apex ≥50% transmurality. Hybrid transcatheter and minimally technique (BioVentrix Revivent TC) that relies on micro-anchoring technology is used to reconstruct the LV by plication of the fibrous scar. A series of internal and external anchors are brought together over a PEEK (poly-ether-ether-ketone) tether to form a longitudinal line of apposition between the LV free wall and the anterior septum from the mid-ventricle to the apex. Internal anchors are deployed by transcatheter technique on the right side of the ventricular septum. External anchors are advanced through a left sided mini-thoracotomy and the anchor-pairs are brought together under measured compression forces. Additional external apical anchor pairs complete the reconstruction. <h3>Results</h3> Between October 2016 and October 2021 29 patients (24 males, 5 females; mean age 62 ± 12 years) were operated in a single Dutch centre. On average 2.3 ± 0.8 anchor-pairs were used for reconstruction. Comparing echocardiographic data pre- and directly postoperatively, LVEF increased from 33 ± 8 to 44 ± 10% (change +35%, P<0.001) and LV-volumes decreased: LVESVI 56 ± 27 to 35 ± 19 ml/m² (change -36%, P<0.001) and LVEDVI 85 ± 33 to 59 ± 25 ml/m² (change -30%, P<0.001). Hospital mortality was 0%. and median length of hospital stay was 7 days (IQR 5-61 days). Survival at 60 months was 86%. At latest follow-up, 85% of surviving patients were in NYHA-class I-II compared to 19% preoperatively. <h3>Conclusion</h3> Hybrid transcatheter and minimally invasive LV reconstruction is a promising treatment option for patients with symptomatic HF after AMI. Five-year results demonstrate that the procedure is safe and results in significant improvement in EF, reduction in LV volumes and sustained improvement in symptoms.

Impact of a cardio-oncology unit on prevention of cardiovascular events in cancer patients.

AimsAs the world population grows older, the co‐existence of cancer and cardiovascular comorbidities becomes more common, complicating management of these patients. Here, we describe the impact of a large Cardio‐Oncology unit in Southern Italy, characterizing different types of patients and discussing challenges in therapeutic management of cardiovascular complications.Methods and resultsWe enrolled 231 consecutive patients referred to our Cardio‐Oncology unit from January 2015 to February 2020. Three different types were identified, according to their chemotherapeutic statuses at first visit. Type 1 included patients naïve for oncological treatments, Type 2 patients already being treated with oncological treatments, and Type 3 patients who had already completed cancer treatments. Type 2 patients presented the highest incidence of cardiovascular events (46.2% vs. 12.3% in Type 1 and 17.9% in Type 3) and withdrawals from oncological treatments (5.1% vs. none in Type 1) during the observation period. Type 2 patients presented significantly worse 48 month‐survival (32.1% vs. 16.7% in Type 1 and 17.9% in Type 3), and this was more evident when in the three groups we focused on patients with uncontrolled cardiovascular risk factors or overt cardiovascular disease at the first cardiologic assessment. Nevertheless, these patients showed the greatest benefit from our cardiovascular assessments, as witnessed by a small, but significant improvement in ejection fraction during follow‐up (Type 2b: from 50 [20; 67] to 55 [35; 65]; P = 0.04).ConclusionsPatients who start oncological protocols without an accurate baseline cardiovascular evaluation are at major risk of developing cardiac complications due to antineoplastic treatments.

THE EVALUATION OF THE TREATMENT WITH THE EXERCISE TISSUE DOPPLER ECHOCARDIOGRAPHIC PARAMETERS WITH NEBIVOLOL TREATMENT IN PATIENTS WITH HEART FAILURE

Objective: Heart failure is one of the most important disease which threats population’s health. Its prevalance increases both in our country and in the world in years. Nebivolol is a molecule which is proved its efficacy in the treatment of heart failure. The aim of this study was to evaluate the changes in echocardiographic parameters such as tissue doppler imaging and myocardial performance index (MPI) after 6 months of nebivolol treatment in patients with heart failure. Method: 20 patients with heart failure were enrolled to the study The average age was 59.8 ± 8.4 years (15 men, 5 women). During rest and exercise (cycle ergometer) we recorded conventional and tissue doppler parameters. In the first examination we recorded basal measurements. Then nebivolol treatment was administered. After 6 months nebivolol treatment we measured again same echocardiographic parameters. Results: The average Ejection fraction (EF) of patients with heart failure in this study was %38.85 ± 6.45 in the first examination. The average EF was increased to %40.95 ± 5.47 in the end of the study (p<0.05). After 6 months nebivolol treatment both during rest and exercise we found significant improvements in the tissue doppler parameters and MPI. Conclusions: Nebivolol is associated with significant improvements in EF in the patients with heart failure. In addition, both during rest and exercise, it’s associated with improvements in tissue doppler parameters which can show beneficial effect on the prognosis of this group of patients.

Systemic delivery of large-scale manufactured Wharton's Jelly mesenchymal stem cell-derived extracellular vesicles improves cardiac function after myocardial infarction.

Introduction:Cardiovascular disease and myocardial infarction are leading causes of morbidity and mortality in aged populations. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are under evaluation as a therapeutic option for the treatment of myocardial infarction.Aim:This study aimed to develop a large-scale manufacturing procedure to harvest clinical-grade EVs required for the translation of EVs to the clinic.Methods and Results:We compared the efficiency of large scale MSC-derived EV production and characterized EV miRNA cargo using the Quantum bioreactor with either fetal bovine serum or human platelet lysate (PLT)-containing expansion media. We tested the potency of the EV products in a murine model of acute myocardial infarction. Our results demonstrate an advantage of the Quantum bioreactor as a large-scale platform for EV production using PLT media; however, both media produced EVs with similar effects in vivo. The systemic delivery of EV products improved cardiac function following myocardial infarctions as indicated by a significant improvement in ejection fraction as well as parameters of cardiac performance, afterload, contractility and lusitropy.Conclusion:These findings have important implications for scale-up strategies of EVs and will facilitate clinical trials for their clinical evaluation.

Improvement of left ventricular function with surgical revascularization in patients eligible for implantable cardioverter-defibrillator.

Left ventricular ejection fraction (EF) ≤ 35% is the cornerstone criterion for implantable cardioverter-defibrillator (ICD) eligibility. Improvement in EF may occur in ICD-eligible patients after coronary artery bypass graft surgery (CABG). However, the incidence, predictors, and outcomes of this process are unclear. We studied 427 patients with EF ≤ 35% who underwent CABG in the Surgical Treatment for Ischemic Heart Failure (STICH) trial and had a systematic pre- and postoperative (4 months) EF assessment using the identical cardiac imaging modality. All imaging studies were interpreted at a core laboratory. Improvement in EF was defined as postoperative EF > 35% and >5% absolute improvement from baseline. Of the 427 patients (mean age 61.8 ± 9.5 and 50 women), 125 (29.2%) had EF improvement. Their mean EF increased from 26.8% (±5.8%) to 43.3% (±6.5%) (p < .0001). EF improvement occurred in only 20% of patients with a preoperative EF < 25%. The odds of EF improvement were 1.96 times higher (95% confidence interval [CI]: 0.91-4.23, p = .09) in patients with myocardial viability. In adjusted analyses, EF improvement was associated with a significantly lower risk of all-cause mortality (hazard ratio [HR]: 0.58, 95% CI: 0.35-0.96; p = .03) and heart failure mortality (HR: 0.31, 95% CI: 0.11-0.87; p = .027). Nearly 1/3rd of ICD-eligible patients undergoing CABG had significant improvement in EF, obviating the need for primary prevention ICD implantation. These results provide patients and clinicians data on the likelihood of ICD eligibility after CABG and support the practice of reassessment of EF after revascularization.

Abstract 13994: Single-Dose Intervention With Rapamycin at Reperfusion Preserves Cardiac Function Through Attenuation of Inflammation and Increased Cardiomyocyte Proliferation in Diabetic Rabbit- Role of Hippo Pathway

Background: Rapamycin (RAPA, mTOR inhibitor) given at reperfusion protects diabetic rabbit hearts against ischemia/reperfusion (I/R) injury by reducing infarct size and apoptosis. We hypothesized that RAPA administration may preserve post-ischemic cardiac function through decreased inflammation and increased cardiomyocyte proliferation with regulation of YAP- the effector of Hippo pathway). Methods and Results: Diabetes (DM) was induced by administration of alloxan monohydrate (125 mg/kg, i.v.) in New Zealand rabbits (n=12; body weight≈3 kg, 4-month-old). Four weeks after alloxan treatments, conscious diabetic rabbits (maintaining blood glucose&gt;250 mg/dL) were subjected to 45 min of ischemia and 10 days of reperfusion (R) by inflating/deflating previously implanted hydraulic balloon occluder. RAPA (0.25 mg/kg, i.v.) or DMSO (vehicle) was infused 5 min before onset of R. Post-I/R cardiac function in diabetic rabbit, assessed by echocardiography, showed significant improvement of ejection fraction (EF, Fig. A ). Left ventricular fibrosis ( Fig. B , evaluated by picrosirius red staining) was attenuated following treatment of RAPA in diabetic rabbits. Immunofluorescence staining revealed the attenuation of post-I/R inflammasome formation with RAPA treatment as shown by reduced ASC aggregation (apoptosis speck-like protein with a caspase recruitment domain) in cardiomyocytes ( Fig. C ). RAPA suppressed the phosphorylation of YAP in cytosol of cardiomyocytes ( Fig. D ). Proliferation markers, Ki-67 positive and phospho-Aurora B Kinase positive cells indicated cardiomyocytes were in G2-M phase in RAPA-treated diabetic rabbits after I/R injury ( Fig. E ). Conclusion: RAPA treatment at reperfusion preserves cardiac function and improves cardiomyocyte proliferation with attenuation of inflammation and possibly regulation of Hippo pathway following I/R injury in diabetes.