Significant Improvement In Ejection Fraction Research Articles

410 Early cardiac reverse remodeling in a large cohort of patients with HFrEF treated with Sacubitril/Valsartan

Abstract Background Despite the widespread use of Sacubitril/valsartan (Sac/Val) in patients with reduced ejection fraction (HFrEF), definite data on cardiac remodeling under treatment are still lacking. Methods We conducted a retrospective analysis on a large cohort of 201 consecutive HFrEF ambulatory patients who started Sac/Val in our HF unit between Sept. 2016 and Dec. 2018 on top of optimal medical treatment. Patients with both basal and follow up (at least 3 months) echocardiographic assessment (TTE) were included. Results A follow up TTE was performed in 100 patients (male 76%; mean age 67.4 ± 11.1 years; medium follow-up 309 ± 182 days). Baseline characteristics are shown in Tab.1. 34% of the patients reached the maximal dose (97/103 b.i.d.) while 18 interrupted the treatment. We observed an overall significant improvement in ejection fraction (EF), end-diastolic and end-systolic ventricular volumes (EDV/ESV), while just a trend in pulmonary pressures (PAPs) and mitral regurgitation (MR) reduction was noted (p = 0.06 and 0.09 respectively). Non ischemic etiology and high dose of Sac/Val were predictors of better remodeling (Fig.1). Conclusion In our study Sac/Val led to an early favorable ventricular remodeling assessed by echocardiography. The observed benefit was greater in patients on higher dose of the drug and non ischemic etiology. Table 1 n = 100 Clinical characteristics Systolic blood pressure (mmHg) 116 ± 11 Diastolic blood pressure (mmHg) 70 ± 9 Hemoglobin (g/dL) 13 ± 2.0 MDRD (ml/min/1.73 m2) 63 ± 21.4 Potassium (mmol/L) 4.26 ± 0.50 NYHA class II (n;%) 59 (59%) NYHA class III (n;%) 41 (41%) Ischemic etiology (n;%) 58 (58%) ICD (n;%) 41 (41%) CRT (n;%) 32 (32%) Beta-blockers (n;%) 94 (94%) ACEi or ARBs (n;%) 92 (92%) MRA (n;%) 77 (77%) Baseline clinical characteristics Abstract 410 Figure. Fig. 1

P1587 Echochardiographic estimation of the impact of long-term treatment with Trimetazidine on myocardial dysfunction in patients with ST elevation myocardial infarction

Abstract Outcome of ST elevation acute myocardial infarction (STEMI) is usually complicatedby congestive heart failure (HF) that impacts quality of life and prognosis. Spectrum of myocardial injury depends on intensity of impaired myocardial perfusion and on existing metabolic state. Metabolic changes occurring during early hours of myocardial infarction include increased secretion of catecholamines and production of circulating free fatty acids (FFAs). As myocardium depends on aerobic metabolism increased FFAs exert toxic effect on myocardium resulting in metabolic mismatch, decreased cardiac function and arrhythmias. Our aim was to diminish signs of HF after STEMI especially in patients (P)who could not undergo reperfusion therapy because of different reasons.We used long-term metabolic therapy (MT) with TrimetazidineMR(TMZ)just from the first day of STEMI during 3 months. Evaluation of heart function was based on ECG, Holter monitoring and echocardiographic (Echo) data received before and after treatment. We observed 50 P with STEMI who could not undergo reperfusion therapy. All were treated with standard therapy according to guideline. 35 of them (I group) additionally were treated with TMZ 80 mg p/o once a day for 3 months. The rest15 patients represented II - control group. P including in these groups were comparable according to echocardiographic data. These Patients did not reveal any life-threatening arrhythmias in the acute stage of MI and any prognostically indifferent arrhythmias in the following period. Echoinvestigation in dynamic (before treatment and after 3 months) showed significant improvement of ejection fraction (EF by 14,2%) and stroke volume (SVby14,8%) in patients with STEMI treated with TMZwhile in control group EF (by 4,5%) and SV (by 6,8%) wereincreasedslightly. After 3 months improvement of diastolic function was also prominent in patients treated with TMZ that was revealed by decreased diastolic volume. In patients treated with MT end diastolic diameter (EDD) diminished by 4,8%, end systolic diameter (ESD) - by 5,7%, end diastolic volume (EDV) - by 9,3% and end systolic volume (ESV) - by 14,9% while in control group EDD was decreased by 1,9%, ESD - by 2,8%, EDV - by 4,7% and ESV - by 4,1%. Diastolic dysfunction was also estimatedaccording to left ventricular filling pressure (LVFP) E/ethat was especially interesting in P with HF with mid-range and preserved EF. Before treatment (LVFP) was increased in 17 P from the first group and in 7 P in control group. In the first group increased LVFP significantly decreased in 12 P and moderately in 5, while in control group LVFPwas only decreased moderately in 4and slightly in 3 P. The received data make it relevant to useTMZmetabolic therapy for effective treatment of HF in patients with STEMI. MT not only improves the course of disease, but diminishes rehabilitation period as well.

Prognosis of heart transplant patients in Mashhad University of Medical Sciences.

IntroductionHeart transplant is the ultimate treatment for patients with end-stage heart failure.AimTo assess 50 heart transplant patients for underlying diseases, transplantation outcome and mortality rate during a 5-year follow-up program.Material and methodsFifty heart transplant patients who underwent heart transplantation from 2012 to 2017 were assessed for underlying diseases, organ rejection, duration of hospitalization, extubation time, cardiac output and survival. Biopsy samples were obtained after surgery for evaluation of rejection.ResultsDilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) were the most common underlying diseases with prevalence of 56% and 12%, respectively. Significant improvement in ejection fraction was observed following heart transplant. Minimum and maximum extubation and hospitalization times were 3–408 hours and 1–51 days, respectively. Organ rejection evaluation 10 days after heart transplantation revealed that 50% of patients did not show any rejection while 10% had severe rejection. At 30 days post-operatively the number of patients with grade III rejection decreased to 2% while 56% of patients had no sign of rejection. The 5-year survival rate was 66% while infection and arrhythmia were the most common causes of death.ConclusionsDCM and ICM are considered the most prevalent underlying diseases in heart transplant candidates. Ejection fraction reached normal ranges following transplant, which provides good quality of life. Low incidence of severe acute rejection demonstrates the effectiveness of our immunosuppressive therapy. In the cases of increased rejection, the patient’s immunosuppressive regimen was re-assessed accordingly.

P318Exosomes mediate myocardial regeneration of cardiac progenitor cells in a swine model of dilated cardiomyopathy

Abstract Introduction Stem cell therapy has been shown to improve cardiac function. The mechanisms of therapeutic efficacy are considered the secretion of paracrine factors but the details are still unknown. Hypothesis Exosomes are extracellular vesicles containing bioactive substances such as proteins, messenger RNAs and micro RNAs. We hypothesized that exosomes may be the main paracrine factors to mediate therapeutic efficacy of cardiosphere-derived cells (CDCs). Methods Farm pigs (30 kg, n=10) were treated by intracoronary administration of 10,000 microspheres (100–300 μm) into three vessels. Two weeks later, 9.0×106 CDCs pretreated by exosome inhibitor (EI; 20μM of GW4869) or DMSO as controls were selectively infused into three coronary arteries. Evaluation of ejection fraction (EF) was performed before cell infusion and 1 month after protocol treatment. Results Pigs developed diffuse hypokinetic heart failure (baseline EF 37.1%±2.1%) and randomly assigned into two groups (CDCs with EI: n=5, CDCs with DMSO: n=5). No serious adverse events were found during the CDCs infusion. Significant improvement of EF was observed in CDCs with DMSO group (37.1%±2.1% to 42.5%±3.0%; P=0.01), whereas no change was found in CDCs with EI group (37.1%±2.4% to 36.2%±2.9%; P=0.58). Myocardial fibrosis stained by picrosirius red was significantly reduced in CDCs with DMSO group compared with CDCs with EI group (9.5±3.6% versus 17.3±5.3%; P<0.01). Conclusions We confirmed the therapeutic efficacy of CDCs and these effects were mainly mediated by exosomes.

P2517Feasibility and safety of cardiac rehabilitation program during Ramadan fasting among patients having coronary artery disease and moderate left ventricular dysfunction

Abstract Background Ramadan fasting (RF) is an important worship activity for Muslims. It entails complete abstinence of food and fluids from dawn to sunset (14–16 hours) for 30 days. The safety and feasibility cardiac rehabilitation program during (RF) is largely unknown. Aim To assess safety and feasibility of cardiac rehabilitation program (CRP) during (RF) in patients with coronary artery disease (CAD) with moderate left ventricular dysfunction (LVD). Moreover, to study the effect of (RF) on some blood parameters Patients and methods Fifty three patients joining (CRP) at our university hospital were included in the study. All had (CAD) with moderate (LVD). Patients were divided into two groups according to their Ramadan fasting status. Group I (fasting) were 32, while group II (non fasting) were 21. All patients underwent exercise training during cardiac rehabilitation in Ramadan. Serum lipid profile, plasma osmolality, renal functions, echocardiography and exercise parameters were assessed before and after (CRP).Clinical follow up was available for one month post Ramadan. Results The two groups were similar in baseline characteristics including: risk factors, serum osmolality, urea, creatinine, lipid profile, hemoglobin values, ejection fraction and exercise parameters.All patients successfully completed the (CRP). No patient in group I had any ischemic episode or exacerbation of (LVD) during or one month after the end of Ramadan.After the program, both groups showed significant improvement in ejection fraction (group I: 43±2% to 52±2%, p<0.001, group II: 41.1±4 to 47.2±3%. p<0.002), total cholesterol (group I: 174.8±40.8 to 169.4±37.1 mg%, p=0.034, group II: 172.9±43.3 to 163.0±40.7 mg%, p=0.01), LDL: Group I: 100.7±33.4 to 94.5±261 mg%, p=0.023, group II: 104.5±42.1 to 93.8±33.8 mg%, p=0.005), and HDL: Group I: 42.7±10.6 to 44.5±10.9 mg%, p=0.029, group II: 40.6±8 to 45±8.9 mg%, p<0.001). However, triglyceride levels improved significantly only in group I (162.3±65.4 to 152.8±52.3 mg%, p=0.042, group II: 144±60 to 133.9±48.8 mg%, p=0.149) l. There was also similar improvement in exercise duration after (CRP) in both groups. It is worthy to note that fasting did not increase the serum osmolality in group I (277.91±15.14 before, and 281.01±11.61 mmol/L after (RF), p value= 0.34) Conclusion Cardiac rehabilitation is feasible and safe among patients with (CAD) and (LVD) during (RF). Moreover, (RF) resulted in significant improvement in serum triglycerides without change in plasma osmolality denoting absence of hemoconcentration despite fasting.

P5981Impact of radiotherapy on myocardial function and paravalvular leaks after transcatheter aortic valve implantation (TAVI)

Abstract Introduction Thanks to the anticancer therapies, the life expectancy of the oncologic patients has noticeably increased, but several cardiac diseases can be observed in these patients as the result of the cardiotoxic effects. Purpose To investigate the impact of radiotherapy on the clinical and echocardiographic outcomes, in patients with severe aortic stenosis (AS) and preserved left ventricle ejection fraction (LVEF) treated with transcatheter aortic valve implantation (TAVI). Methods We recruited patients with severe AS and left ventricular ejection fraction (LVEF) ≥50‰ treated with TAVI and who received prior radiotheraphy. Patients with LVEF <50‰, treated with valve in valve, with inadequate acoustic windows or the absence of echocardiographic images pre-TAVI and after 3–6 months were excluded. Demographic, clinical and echocardiographic data were recorded. Results 102 patients were included in the present analysis. They were divided in two groups: 19 (18‰) with an oncologic history treated with previous left thoracic/mediastinal radiotherapy and 83 (82‰) patients without an oncologic history. The two groups were homogeneous in terms of demographic and clinical data, brain natriuretic peptide (BNP), echocardiographic data pre-TAVI. They only differed for a greater prevalence of mitral stenosis and calcifications in the oncologic patients versus the non-oncologics (respectively 36‰ vs. 12‰ p=0,016; 73‰ vs. 29‰ p=0,001). No differences in terms of in-hospital clinical outcomes were observed. The echocardiographic evaluation in both groups showed a significant decrease of the peak velocities and of the transprosthetic gradients. There was a higher incidence of at least moderate degree paraprosthetic leaks in the oncologic group vs. the non-oncologic one: 6 (31‰ total leaks, 37‰ leaks >2+) vs. 7 (8‰ total leaks, 12‰ leaks >2+); p=0.029. After 3–6 months, there was not a statistically significant improvement of ejection fraction (EF) in neither of the two groups but there was a statistically significant improvement of transmural, subepicardial and subendocardial longitudinal strain values in the non-oncologic group compared to pre-TAVI values, respectively −19±4 vs. −17±4 (p<0.001); −17±3 vs. −15±3 (p<0.001); −22±4 vs. −19.8±4 (p<0.001). Any statistically significant improvement was detected in the group with history of anticancer treatments between the longitudinal strain values post and pre-TAVI (−18±3‰ vs. −16±3‰; −14±3‰ vs. −20±5‰; −20 ±± 5‰ vs. −19±4‰). Conclusions Patients affected by severe AS treated with TAVI and who received received prior radiotheraphy, showed the absence of statistically significant improvement of multilayer strain values, at 3–6 months after TAVI. Oncologic patients also had a higher incidence of haemodynamically relevant paravalvular leaks after the intervention, compared to the non-oncologic patients.

A Study of Intracoronary Injection of Hematopoietic Stem Cells in Pediatric Dilated Cardiomyopathy: Is It an Applicable Solution for Critically Ill Patients?

Background: Benefits of stem cell therapy on remodelling and cardiac function have been described in adults with dilated cardiomyopathy and acute myocardial infarction. Objectives: We investigated the effect of this treatment modality amongst children with severe dilated cardiomyopathy. Methods: Intracoronary injection of autologous bone marrow mononuclear stem cells was performed in our centers for 8 severely ill children during 2015 - 2016. The mean age of the patients was 10.1 years (5 girls, 3 boys). They were followed by longitudinal speckle tracking echocardiography (STE) and conventional echocardiography for 6 months. Results: Heart functional class improved in 62% of patients. M-mode echocardiography showed significant improvement in ejection fraction (mean 24.8 ± 8.3 vs. 37.4 ± 10.5) and in STE, the mean global longitudinal strain improved (GLS: -2.8 ± 1.9 vs. -5.2 ± 3.9). None of the patients had serious complications. Conclusions: Intracoronary injection of autologous mononuclear stem cells might improve the ventricular function and cardiac remodelling in pediatric patients with dilated cardiomyopathy and could be considered in critically ill patients.

Pioglitazone strengthen therapeutic effect of adipose-derived regenerative cells against ischemic cardiomyopathy through enhanced expression of adiponectin and modulation of macrophage phenotype

BackgroundThe efficacy of cell transplantation in heart failure is reportedly modest, but adjuvant drugs combined with cell therapy may improve this efficacy. Peroxisome proliferator-activated receptor (PPAR)γ, one of the hypoglycemic medicine for diabetes mellitus, reportedly enhances cytokine production in adipose tissue-derived regenerative cells (ADRCs). We hypothesized that combined administration of PPARγ agonists and ADRCs may enhance the paracrine effects of adiponectin (APN), leading to functional recovery in a chronic myocardial infarction (MI) model.MethodsADRCs were isolated from adipose tissues of adult rats by gradient centrifugation and embedded in bio-compatible fibrin-glue to produce ADRCs grafts. In the in vitro study, the ADRCs grafts released APN, which was significantly enhanced by the PPARγ agonist (PGZ, pioglitazone). Transplantation of ADRCs grafts (group A), ADRCs mixed with PGZ (group AP), APN knockdown-ADRCs (group Si) or PGZ (group P) onto the epicardium or a sham operation (group C) was performed (n = 10–20 per group).ResultsThe AP group showed significant improvement in ejection fraction compared to that in the other groups. In the AP group, a significantly larger number of M2-polarized macrophages was detected and existed for a significantly longer duration in the infarct area. Furthermore, comparing Si group and P group, western blotting of T-cadherin revealed that exogenous APN and local expression of T-cadherin were essential to this histological change and recovery of cardiac function.ConclusionsCombined administration of PPARγ agonist and ADRSCs activated M2-polarized macrophages with enhancement of APN paracrine effects and lead to better cardiac function in a rat infarction model.

Effect of cardiac resynchronization therapy on quality of life: Role of hypertension

Aims: To evaluate cardiac function, quality of life and role of hypertension in symptomatic heart failure in patients with Cardiac Resynchronization Therapy (CRT). Methods: 80 patients with heart failure were enrolled in our study. Among them 30 patients underwent CRT implantation (CRT group) and 50 patients received optimal medical therapy only (non-CRT group). Follow-up was carried out for 20 ± 2.828 months. Assessment of New York Hear Association (NYHA) class, QRS width, Ejection Fraction (EF), left ventricular end diastolic diameter, left ventricular end systolic diameter, interventricular septum, posterior wall thickness, degree of Mitral Regurgitation (MR) and Basic Natriuretic Peptide (BNP) level was performed at baseline and follow-up along with number of admissions and Quality of Life (QOL) assessment. Results: The baseline indices of patients in the CRT and non-CRT groups were statistically same (P>0.05). At the end of follow-up most indices showed significant improvement in the CRT group (P<0.05) except thickness of IVS and the PWT (P>0.05). The indices in the non-CRT group only showed significant improvement in EF and BNP level (P<0.05). Hypertensive patients did not show significant impact on number of admissions and QOL (P<0.05). Conclusions: Patients receiving CRT had an overall improved outcome with beneficial effects in cardiac remodeling, enhancing the left ventricular function and improving the quality of life. Hypertension was associated with poorer outcome

Evaluation of a guideline directed medical therapy titration program in patients with heart failure with reduced ejection fraction

IntroductionHeart failure is associated with recurrent hospitalizations and high mortality. Guideline directed medical treatment (GDMT), including beta blockers (BBs), angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs) and aldosterone antagonists (AAs) has shown to improve outcomes. Current guidelines recommend the use of these medication classes at maximally tolerated dosages. Despite the evidence, < 25% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) are on the appropriate medical regimen titrated to the target doses. As such, we sought to assess the utility of a focused GDMT clinic to reduce this gap. MethodsWe conducted a retrospective chart review through existing patient data in a single center teaching hospital of patients referred to a focused GDMT clinic primarily staffed with heart failure trained nurse specialists, physician assistants and cardiologists. Management guidelines were developed with protocols for the initiation and uptitration of all therapeutic agents considered as GDMT.Our primary objective was to determine whether enrollment into a dedicated nursing led guideline directed medical therapy clinic would increase the proportion of patients with heart failure with reduced ejection fraction on appropriate medications as well as medication dosages in patients, the percentage of patients on the following medications and percentage at target doses: Renin-Angiotensin-Aldosterone System Blockers, Evidence Based Beta Blockers, and Aldosterone Antagonists. Our secondary objective was to determine if there was any clinical benefit on objective measures including renal function, hospital admissions, mortality and implantable defibrillator shocks. ResultsBetween October 2015 and March 2017, 63 patients were identified by requisition forms, in which 61 were able to be identified based on legibility of identifying information. Mean duration of follow up was 264.44 ± 162.68 days over 7 ± 3.94 days. Mean ejection fraction was 21.8 ± 7.3%. New onset cardiomyopathies (diagnosed within 30 days) compiled 21% of the patient population while those with demonstrated cardiomyopathies (> 90 days) compiled 48% of the patient population. Patients with NYHA class III heart failure compiled 65% of the patient population.There was a statistically significant increase in the mean number of GDMT at any dose (2.31 ± 0.76 to 2.74 ± 0.66; p < 0.001) and mean number of GDMT at target doses (0.54 ± 0.79 to 1.52 ± 1.1; p < 0.001). Percentage of the population that were on no target doses at initial visit was 62% which was reduced to 18% after intervention.Clinical improvement was reflected in significant improvement in ejection fraction from 21.8 ± 7.8% to 36.2 ± 14.3% (p < 0.001). Increases in sodium and chloride were statistically small but significant. There a significant reduction in heart failure hospitalizations in comparison to a year prior to after the initial encounter in the clinic (p < 0.001). ConclusionThis pilot study showed that a nurse directed GDMT titration program successfully increased the number of GDMT that patients were able to tolerate in a timely fashion, all the while enhancing ejection fraction, sodium and chloride levels, with a reduction in rehospitalization rates.

Abstract 16932: Glucagon-Like Peptide 1 Receptor Agonist Mitigates Postinfarction Adverse Left Ventricular (LV) Remodeling in Mice; a Mechanism Linked to Mitophagy and the Restoration of Cardiac Fatty Acid Oxidation

Glucagon-like peptide 1 receptor agonist (GLP1Ra) and its variants have been shown to protect against cardiac ischemic injury. Less is known about their effects on adverse post-MI LV remodeling. Based on our observation that GLP1Ra stimulated mitophagy in H9C2 cardiac cells, we evaluated its effects on post-MI remodeling. Mice underwent permanent coronary artery ligation (PCAL), ensuring remodeling would be independent of changes in infarct size. Vehicle or GLP1Ra (Sigma) were administered i.p. 2h after the infarct and then every other day for a total of 6 doses. LV remodeling was assessed 30 days post-MI via echo. Histology was used to examine immune cell infiltration 7 days post-MI (early phase) via hematoxylin and eosin staining, and fibrosis by Masson’s trichrome after 30 days (late phase). GLP1Ra-treated mice exhibited a marked reduction in immune cell infiltration ( A ), and fibrosis ( B ). This corresponded to a significant improvement in ejection fraction (EF) and fractional shortening (FS) ( C ), although not to the levels of sham-operated mice (EF 60% and FS 30%, data not shown). We assessed the importance of GLP1Ra-induced mitophagy in Parkin KO (PKO) mice. GLP1Ra failed to attenuate adverse remodeling ( D and E ) and immune cell infiltration ( F ) in PKO mice implicating the importance of mitophagy as an underlying mechanism. We next determined the effect of GLP1Ra on the activation state of the pyruvate dehydrogenase complex (PDC), which governs substrate utilization. Ischemically injured hearts shift fuel use towards carbohydrate oxidation, which we confirmed in our PCAL model via decreased phosphorylation of the PDC. Post-MI administration of GLP1Ra promoted PDC phosphorylation and thereby restored fatty acid utilization during the early phase of remodeling ( G and H ). These findings suggest that alterations in cardiac metabolic poise after ischemic injury play a role in adverse remodeling and that stimulation of mitochondrial turnover influences this process.

Prospective evaluation of left atrial function and late gadolinium enhancement with 3T MRI in patients with atrial fibrillation before and after catheter ablation.

In a prospective, randomized study we performed left atrial (LA) functional imaging and late gadolinium enhancement (LGE) in patients undergoing pulmonary vein isolation with ablation of the anterior mitral line to evaluate LA function and visibility of the anterior mitral line and to explore the relationship of these factors to short- and long-term procedural success. Functional imaging of the LA and LGE-visualization 15min post i.v. administration of gadobutrol was performed on a 3T MRI system before and after ablation. Patients were grouped in (a) subjects with sinus rhythm, and (b) subjects without sinus rhythm at the follow-up-MRI. Eight patients were excluded due to poor image quality. 37 patients were allotted to group a, 4 patients to group b. Group a showed a significant improvement in ejection fraction (22.3 ± 7.1% vs. 27.2 ± 5.5%; p < 0.001), end-systolic volume (111.6 ± 48.3ml vs. 96.9 ± 37.2ml; p = 0.002), stroke volume (30.2 ± 12.6ml vs. 35.6 ± 12.6ml; p = 0.003) and LGE (12.5% vs. 83.7%; p < 0.001). Group b showed no significant changes in functional parameters or LGE. Patients with successful therapy at 12months showed significantly lower volumes in the baseline MRI. Scarring along the ablation pathways could be visualized with LGE. Patients with successful CA showed a significant improvement in LA cardiac parameters. Pre-ablation atrial volume seems to be a predictor for long-term success.

Transcatheter and minimally invasive surgical left ventricular reconstruction for the treatment of ischaemic cardiomyopathy: preliminary results†.

Adverse remodelling of the left ventricle (LV) after myocardial infarction (MI) results in a pathological increase in LV volume and reduction in LV ejection fraction (EF). We describe the preliminary results of a novel, multicentre, combined transcatheter and minimally invasive technique to reconstruct the remodelled LV by plication and exclusion of the scar, and to reduce the excess volume, resulting in decreased wall stress and increased EF. A novel hybrid transcatheter technique that relies on microanchoring technology (Revivent TC™ System, BioVentrix Inc., San Ramon, CA, USA) was used. The LV is reconstructed without the use of extracorporeal circulation by plication of the fibrous scar. This is achieved by implantation of a series of internal and external microanchors 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. Internal anchors are deployed by a transcatheter technique on the right side of the ventricular septum through the right internal jugular vein. Paired external anchors are advanced through a left-sided minithoracotomy and deployed on the LV epicardium. A specialized force gauge is used to bring these 'right ventricle (RV)-LV' anchors together under measured compression forces. LV-LV' anchor pairs through the LV apex beyond the distal tip of the RV complete the reconstruction. Patients who were considered eligible for the procedure presented with symptomatic heart failure (New York Heart Association class ≥II) and ischaemic cardiomyopathy (EF <40%) after anteroseptal MI. All patients had a dilated LV with either an a- or dys-kinetic scar in the anteroseptal wall and apex of ≥50% transmurality. Between October 2016 and April 2017, 9 patients (8 men, 1 woman; mean age 60 ± 8 years) were operated on in 2 Dutch centres. Procedural success was 100%. On average, 2.6 anchor pairs were used to reconstruct the LV. Comparing echocardiographic data preoperatively and directly postoperatively, LV ejection fraction increased from 28 ± 8% to 40 ± 10% (change +43%, P < 0.001) and LV volumes decreased LV end-systolic volume index 53 ± 8 ml/m2 to 30 ± 11 ml/m2 (change -43%, P < 0.001) and LVEDVI 75 ± 23 ml/m2 to 45 ± 6 ml/m2 (change -40%, P = 0.001). In 1 patient, an RV perforation occurred which necessitated conversion to full sternotomy. One patient underwent a postoperative revision because of RV restriction. After the removal of 1 'RV-LV' anchor pair, the patient recovered completely. Hospital mortality was 0%. The median duration of intensive care unit stay was 2 days [interquartile range (IQR) 1-46 days], and the median length of hospital stay was 9 days (IQR 3-57 days). Hybrid transcatheter LV reconstruction is a promising novel treatment option for patients with symptomatic heart failure and ischaemic cardiomyopathy after anteroseptal MI. The early results demonstrate that the procedure is safe and results in a significant improvement in EF and reduction in LV volumes in the early postoperative period.

Abstract 395: Pioglitazone and Glucagon-like Peptide 1 Receptor Agonist Mitigate Adverse Postinfarction Left Ventricular Remodeling in Lean Mice When Administered After the Infarct Independent of Changes in Infarct Size

Pioglitazone (PIO) and GLP-1R receptor agonist (GLP1Ra) have been shown to be cardioprotective against ischemic cardiac injury. Much less is known about the effects of these agents on adverse post-MI LV remodeling. Based on our earlier findings that PIO and a GLP1Ra stimulate mitochondrial turnover, we evaluated the effects of these agents on post-MI remodeling. Lean mice underwent permanent coronary artery ligation (PCAL) to ensure that remodeling would be independent of changes in infarct size. Vehicle, PIO and GLP1Ra (Sigma) were administered i.p. 2h after the infarct and then every other day for a total of 6 doses. Echo and histology (Masson’s trichrome) were used to assess LV remodeling 30 days post-MI (late phase); immune cell infiltration was assessed 7 days after PCAL (early phase) via hematoxylin and eosin (H&amp;E) staining. Both PIO and GLP1Ra were associated with significant improvements in ejection fraction and fractional shortening (A); however, at the dose used, neither drug restored function to that of the sham-operated mice (EF 60% and FS 30%, data not shown). GLP1Ra-treated mice exhibited a marked reduction in immune cell infiltration at 7d after PCAL (B), and fibrosis at 30d (C) compared to vehicle or PIO. While PIO had no effect on immune-cell infiltration and fibrosis, it was effective in attenuating post-MI remodeling. While sharing a common endpoint of attenuating adverse remodeling, the finding that PIO stimulates mitochondrial biogenesis and GLP1Ra induces mitophagy may help explain their disparate findings with respect to early phase remodeling.

Predictors of myocardial functional recovery following successful reperfusion of acute ST elevation myocardial infarction.

Following acute ST elevation myocardial infarction (STEMI), restoration of large-vessel patency does not mean complete perfusion recovery. Little is known regarding the predictors of successful myocardial reperfusion for the STEMI patients undergoing pharmacologic and mechanical reperfusion strategies. The aim of this clinical study was to find out the predictors of myocardial functional recovery following reperfusion of acute STEMI, represented by 3-month global longitudinal strain (GLS) value assessed by speckle tracking echocardiography. The study population included 400 patients presented with first acute STEMI with successful reperfusion by thrombolysis (group I) or primary percutaneous coronary intervention (PPCI) (group II). Electrocardiography (ECG) at baseline and 90minutes after coronary reperfusion was performed with assessment of ST resolution. Basal and 3-month follow-up echocardiography was performed with assessment of ejection fraction (EF), myocardial performance index (MPI), systolic myocardial excursion (S'), and GLS. There was nonsignificant difference between patients of both groups regarding age (P=0.422) and gender (P=0.272). Also, there was a nonsignificant difference between both groups regarding the risk factors of coronary artery disease like hypertension (P=0.511), diabetes mellitus (P=0.332), and smoking (P=0.381). But there was significant statistical difference between both groups regarding dyslipidemia (P=0.012). Ninety-minute ST resolution was significantly higher in PPCI group (P=0.042). Moreover, PPCI group had significant improvement of EF (P=0.013) during follow-up, and highly significant improvement of MPI, S' and GLS (P˂0.001) compared to the basal echocardiographic study. The percentage of change (∆) of each of the echocardiographic parameter was compared between both groups and revealed statistically significant improvement regarding EF, highly significant improvement of MPI, S' and GLS in favor of PPCI arm (group II). Multivariate regression analysis demonstrated that pain to reperfusion time, MI territory, ST resolution, and basal GLS value are the most important predictors for LV functional recovery. The study found pain to reperfusion time, MI territory, ST resolution, basal GLS value are the most important predictors of myocardial functional recovery. Regular follow-up with echocardiography for STEMI patients with different reperfusion strategies has informative impact on long-term clinical outcome. Also the study confirmed that PPCI is better than thrombolysis not only in restoring epicardial coronary flow but also in restoring microvascular and tissue perfusion assuring better myocardial functional recovery and better long-term clinical outcomes.

The Impact of a Nurse Led Guideline Directed Medical Therapy Clinic

Background Heart failure with reduced ejection fraction (HFrEF) is a leading cause of rehospitalizations, high morbidity and mortality. Current guidelines recommend the use of Guideline Directed Medical Therapy (GDMT) at maximum tolerated doses which have shown to improve outcomes. Unfortunately, Methods We conducted a retrospective chart review of existing patient data in a single center teaching hospital of patients referred to a nurse led GDMT clinic primarily staffed with heart failure trained nurses, physician assistants and cardiologists. Protocols for the initiation and uptitration of GDMT were developed based on existing guidelines. Our primary objective was to determine whether enrollment into a nurse led GDMT clinic would increase the proportion of patients with HFrEF on appropriate medications at doses. Our secondary objective was to determine the benefit on renal function, hospital admissions, mortality and implantable defibrillator shocks. Results Between November 2015 to November 2017, 61 patients were enrolled into the clinic. Mean duration of follow up was 264.44 days. Mean ejection fraction (EF) was 21.8%. New onset HFrEF (diagnosed 90 days) comprised 48% of the population. Patients with NYHA class III comprised 65% of the population. There was a statistically significant increase in the mean number of GDMT at any dose (2.31 to 2.74; p: Fig 1 ). There was a significant increase in utilization of ARNI and AA while a significant decrease in utilization of ACE-I ( Fig 2 ). There was a significant improvement in EF from 21.8% to 36.2% (p: Conclusions This pilot study showed that a nurse led GDMT titration program successfully increased the number of GDMT at target doses that patients were able to tolerate, all the while enhancing functional status, EF, sodium and chloride levels, with a reduction in rehospitalization rates.

The Structure‐function Remodeling and Therapeutic Effect of Tongxinluo Capsule in Rabbit Hearts of Myocardial Infarction

ObjectiveAnimal models are important to study basic mechanism of ischemic heart failure (HF). The objective of the study was to create rabbit models of myocardial infarction to investigate the structure‐function remodeling of the left ventricle (LV) and coronary arterial trees and the therapeutic effects of Tongxinluo Capsule.MethodNew Zealand white rabbits were randomly divided into sham group, model group and therapeutic group. The rabbit models were created through multiple coronary artery ligations. Echocardiographic, Micro‐CT and histological measurements were performed at postoperative 6 weeks and postoperative 12 weeks, respectively.ResultEchocardiographic measurements of the model group showed an approximately monotonic slope of ejection fraction and fractional shortening from 73% and 40% to 58% and 28% as well as persistent enlargement of LV cavity and slight mitral regurgitation at postoperative 12 weeks. Measurements of micro‐CT and histology revealed that coronary vascular sparseness and cardiac fibrosis related to inflammation occurred concurrently in adjacent zone of MI at postoperative 12 weeks although there was compensatory vascular growth at postoperative 6 weeks. Compared with the model group, the therapeutic group presented significant improvements in ejection fraction, fractional shortening, LV end‐systolic dimension and volume of cardiac output. The number of capillary vessels increased distinctly, while the infarct area decreased correspondingly.ConclusionsIn conclusion, these findings validate the proposed rabbit model and prove that the interaction of the degenerated coronary vasculature and increased ventricle wall stress relevant to cardiac fibrosis in vicinity of myocardial infarction (MI) facilitates the occurrence and development of ischemic HF. Furthermore, Tongxinluo Capsule has been proved in our study to play an essential role in protecting myocardium, improving blood supply of myocardium and relieving myocardial injury. To summarize, the post‐MI rabbit model can serve as a reference to test various drugs for treatment of ischemic HF, and contributes to the clinical application of Tongxinluo Capsule in the future.Support or Funding InformationThis research is supported in part by the National Natural Science Foundation of China Grant 11372010, 11672006 (Y Huo); Shenzhen Science and Technology Innovation Institution (China) Grant JCYJ20160427170536358 (Y Huo); and Hebei University (China) Grant 2015A1002 (Y Huo).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of SDF-1:CXCR4 in Impaired Post-Myocardial Infarction Cardiac Repair in Diabetes.

Diabetes is a risk factor for worse outcomes following acute myocardial infarction (AMI). In this study, we tested the hypothesis that SDF‐1:CXCR4 expression is compromised in post‐AMI in diabetes, and that reversal of this defect can reverse the adverse effects of diabetes. Mesenchymal stem cells (MSC) isolated from green fluorescent protein (GFP) transgenic mice (control MSC) were induced to overexpress stromal cell‐derived factor‐1 (SDF‐1). SDF‐1 expression in control MSC and SDF‐1‐overexpressing MSC (SDF‐1:MSC) were quantified using enzyme‐linked immunosorbent assay (ELISA). AMI was induced on db/db and control mice. Mice were randomly selected to receive infusion of control MSC, SDF‐1:MSC, or saline into the border zone after AMI. Serial echocardiography was used to assess cardiac function. SDF‐1 and CXCR4 mRNA expression in the infarct zone of db/db mice and control mice were quantified. Compared to control mice, SDF‐1 levels were decreased 82%, 91%, and 45% at baseline, 1 day and 3 days post‐AMI in db/db mice, respectively. CXCR4 levels are increased 233% at baseline and 54% 5 days post‐AMI in db/db mice. Administration of control MSC led to a significant improvement in ejection fraction (EF) in control mice but not in db/db mice 21 days after AMI. In contrast, administration of SDF‐1:MSC produced a significant improvement in EF in both control mice and db/db mice 21 days after AMI. The SDF‐1:CXCR4 axis is compromised in diabetes, which appears to augment the deleterious consequences of AMI. Over‐express of SDF‐1 expression in diabetes rescues cardiac function post AMI. Our results suggest that modulation of SDF‐1 may improve post‐AMI cardiac repair in diabetes. stem cells translational medicine 2018;7:115–124

Intramyocardial bone marrow mononuclear cells versus bone marrow–derived and adipose mesenchymal cells in a rat model of dilated cardiomyopathy

BackgroundEffects of cell therapy on dilated cardiomyopathy (DCM) have been investigated in pre-clinical models using distinct cellular types in each study. A single study that compares the effectiveness of different cells is lacking. MethodsWe have compared the effects of intramyocardial injection (IMI) of bone marrow (BM)–derived mononuclear cells (MNCs), BM and adipose tissue (AT) mesenchymal stromal cells (BM-MSCs and AT-MSCs) on heart function, histological changes and myocardial ultrastructure in a rat model of DCM. Isogenic Wistar rats were used to isolate the different cell types and to induce DCM by autoimmune myocarditis. Animals were randomly assigned to receive BM-MNCs, BM-MSCs, AT-MSCs or placebo at day 42 by IMI. Serial echocardiography was used to assess cardiac function and hearts obtained after sacrifice at day 70, were used for histological and ultrastructural analysis. Serum levels of type B-natriuretic peptide (BNP) and vascular endothelial growth-factor (VEGF) were determined at different time points. ResultsBM-MSC treatment induced significant improvement in ejection fraction (EF), fractional shortening (FS), left ventricular systolic diameter (LVESD) and systolic volume (LVESV). In contrast, changes in echocardiographic parameters with respect to pre-treatment values in animals receiving placebo, AT-MSCs or BM-MNCs were not statistically significant. EF and FS in animals receiving AT-MSCs were superior to those receiving placebo. BM-MSC transplantation induced also improvement in cardiac fibers organization and capillary density, fibrotic tissue reduction, increase in final VEGF concentration and BNP decrease. DiscussionIMI of BM or AT-MSCs improves LV function and induces more angiogenesis processes than BM-MNCs. In addition, BM-MSCs showed more anti-fibrotic effects and more ability to reorganize myocardial tissue compared with the other cell types.

Predictors of adverse effects after coronary artery bypass grafting in patients with reduced left ventricular ejection fraction

BackgroundTo determine adverse outcome and its specific perioperative predictors after coronary artery bypass grafting (CABG) in patients with reduced preoperative ejection fraction (EF). MethodsThis study included two propensity-score matched groups, each of 50 patients. Group I included patients with EF <50% and group II included patients with EF ≥50%. All patients underwent isolated, elective on-pump CABG between November 2014 and October 2016, at Assiut and Minia university hospitals. Preoperative, operative, postoperative and follow-up (6 months) data were collected and analyzed. The primary outcome was early 30 days mortality. ResultsEarly mortality was 8% in group I and 4% in patients in group II. The proportion of low cardiac output syndrome (LCOS) in group I was significantly higher than group II (44% versus 26%, P = 0.04). At the end of 6 months follow-up, most of patients in group I had significant improvement of EF and NYHA class. On multivariate analysis the significant predictors of outcome in group I were insertion of IABP for early mortality, incomplete revascularization for LCOS, sternal wound infection and LCOS for prolonged hospital stay. Preoperative change in wall motion score following dobutamine stress echocardiography (DSE) had good predictive accuracy for early mortality. ConclusionsInsertion of IABP, incomplete revascularization, wall motion scores on DSE, and postoperative LCOS are significant predictors of adverse outcome after CABG in patients with preoperative EF <50% and viable myocardium. A protocol approach should be established for such patients respecting perioperative risk factors.