Cell-Based Therapy in Cardiac Regeneration: An Overview.

Previous studies have demonstrated improvement of regional wall motion and global left ventricular function after successful recanalization of chronic total occlusion in coronary artery. However, the difference of benefits of recanalization between infarct site and noninfarct site is unknown. This study assessed the changes in left ventricular ejection fraction, regional wall motion after successful angioplasty of chronic total occlusions with or without previous myocardial infarction. This study also evaluated the factors that influenced the outcome of left ventricular function. We retrospectively studied 75 patients with a successfully recanalized chronic total occlusion in native coronary artery. Left ventriculograms were obtained at baseline and after 6 months. Global and regional left ventricular function were determined. The patients were divided into two groups. Group 1 comprised patients without previous myocardial infarction in the territories of total occlusion vessel that was recanalized. Group 2 comprised patients with previous myocardial infarction in the territories of total occlusion vessel that was recanalized. Left ventricular ejection fraction increased from 53.2% +/- 16.3% at baseline to 57.3% +/- 20.1% at 6-month follow-up in the whole group (P = 0.001). In group 1 patients, the evolution of left ventricular (LV) ejection fraction increased from 59.5% +/- 13.7% to 67.3% +/- 14.6% (P < 0.001). In group 2 patients, the evolution of LV ejection fraction increased, but not significantly, from 48.9% +/- 16.2% to 50.5% +/- 16.9% (P = NS). The evolution of LV ejection fraction increased from 47.6% +/- 17.4% to 50.8% +/- 17.5% (P < 0.05) in the subgroup of recanalization in infarct-related vessel that had rich collateral circulation and had long-term patency. The regional wall motion all significantly improved in group 1 patients (P < 0.05). The regional wall motion did not change in group 2 patients (P = NS). The influence of recanalization of chronic coronary occlusions on the improvement of left ventricular global function was different between myocardial infarction and nonmyocardial infarction patients. The left ventricular function did not improve in myocardial infarction patient. Regional wall motion improved in patients without previous myocardial infarction. For reliable improvement of left ventricular function after recanalization of chronic total occlusions, evidence (not only by symptom or treadmill test) of viable myocardium in recanalized vessel is important. It is also important to keep patency of infarct-related vessel that has good collateral circulation for improving the left ventricular function.

The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials. We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes. Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.

ACC/AHA/ASE 2003 Guideline Update for the Clinical Application of Echocardiography: Summary Article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to update the 1997 guidelines for the clinical application of echocardiography)

ACC/AHA/ASE 2003 Guideline Update for the Clinical Application of Echocardiography: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography).

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Value of Three-Dimensional Speckle-Tracking Longitudinal Strain for Predicting Improvement of Left Ventricular Function After Acute Myocardial Infarction

ObjectivesThe objective is to perform a meta-analysis of clinical trials that investigated the effects of bone marrow cell (BMC) therapy on left ventricular (LV) function and LV remodelling in patients...

Heart failure (HF) is a major public health and economic problem in Western countries and is one of the most common causes of hospitalization and death. Coronary artery disease is the underlying cause in more than two thirds of chronic HF patients. By 2020, the World Health Organization projects that ischemic heart disease alone will be the most important global cause of morbidity and mortality. The estimated increases in HF-related morbidity and mortality suggest that our understanding of the pathophysiological mechanisms of this syndrome is inadequate. Interest in the role of thyroid hormones (THs) in HF has increased in recent years. The driving considerations can be summarized as follows: (1) the known effects of THs on contractile and relaxation properties of the heart; (2) experimental findings offering strong support for the hypothesis that TH signaling is critical in preserving cardiac structure and performance under normal conditions and after cardiac injury; and (3) evidence that mildly altered TH function is strongly associated with a worsening prognosis in cardiac patients in general and in HF patients in particular. Diastolic function and systolic function are clearly influenced by THs.1 Ventricular contractile function is also influenced by changes in hemodynamic conditions secondary to TH effects on peripheral vascular tone.1 TH homeostasis preserves positive ventricular-arterial coupling, leading to a favorable balance for cardiac work. A study in rats demonstrated that chronic hypothyroidism alone can eventually lead to HF.2 Other studies suggest reduced cardiac tissue triiodothyronine (T3) levels after myocardial infarction (MI) or with development of hypertension by upregulating type 3 deiodinase (D3), which leads to deactivation of T3 and T4 (thyroxine).3–6 This review highlights a growing body of evidence from animal studies and small-scale clinical trials suggesting that low cellular thyroid activity at the cardiac tissue level may adversely affect HF …

Background: Fractional flow reserve (FFR) may provide clinically useful diagnostic information both in patients (pts) with normal left ventricular (LV) function as well as in pts with previous myocardial infarction (MI). However, the question remains to the relation between improvement of FFR and improvement of LV function in pts with previous MI undergoing percutaneous coronary intervention (PCI). Aim: The aim of the study was to evaluate the relation between FFR and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with functional improvement of LV function in pts with previous MI undergoing PCI. Methods: Study population consisted of 50 pts (mean age 53±8 years; 40 male) with previous MI and significant coronary stenosis in one-vessel CAD (33 LAD, 4 Cx, 13 RCA) undergoing PCI of infarct-related coronary artery. In all pts we have evaluated by single pressure/thermo wire FFR and CFRthermo before and immediately after PCI. In all pts, we have evaluated LV ejection fraction by echo and wall motion score index (WMSI) before and 3 months after PCI. Results: Coronary lesions were successfully treated in all pts with decrease of diameter stenosis from 63±7% to 18±9% (p&lt;0.001). FFR increased significantly (p&lt;0.001) from 0.62±0.15 to 0.91±0.06 after PCI, whereas CFRthermo increased significantly (p&lt;0.01) from 1.5±0.3 to 2.5±0.7. LV ejection fraction increased from 49±6% to 55±8% (p&lt;0.0001), and WMSI decreased from 1.44±0.24 to 1.29±0.29 (p&lt;0.0001). LV functional improvement was observed in 33/50 (66%) of pts. In pts with LV functional recovery in comparison to pts with no recovery there was significant difference in FFR before PCI (0.57±0.15 vs. 0.71±0.11, p=0.001), improvement of FFR during PCI (0.34±0.15 vs. 0.21±0.13, p=0.004), improvement of CFRthermo during PCI (1.2±0.6 vs. 0.6±0.5, p=0.001) and CFRthermo after PCI (2.7±0.7 vs. 2.1±0.6, p=0.008), respectively. Conclusion: Evaluation of FFR and CFRthermo provide significant prognostic information on LV functional recovery in pts with previous MI undergoing PCI. Lower FFR before PCI, higher CFRthermo after PCI, as well as higher improvement of FFR and CFRthermo during PCI are indicative of left ventricular functional improvement in pts with previous MI.

Introduction: Gastrointestinal bleeding (GIB) after continuous-flow left ventricular assist device (CF-LVAD) implantation is common, with an incidence estimated at 18-40% per year. While the pathophysiology of GIB in these patients is unclear, physiologic changes related to the absence of pulsatility may account for the high rates of GIB seen in these patients. Hypothesis: Improved left ventricular (LV) function (increased myocardial pulsatility) after LVAD implantation may be associated with decreased rates of GIB. Methods: We studied 119 consecutive patients with CF-LVADs implanted between March 2006-November 2016 who received serial transthoracic echocardiograms (TTE), including at least one pre-implant and one post-implant TTE. Left ventricular ejection fraction (LVEF) was assessed by experienced readers, with a kappa statistic between readers &gt;0.90. Improved LV function was defined as an improvement of at least 7% between the pre-implant LVEF and the best post-implant LVEF obtained with 9 months of the implantation date. Similarly, worsening LV function was defined as a decrease of at least 7%. Primary GIB was defined using INTERMACS adverse event criteria. Patients were followed until transplantation, device complication requiring explantation, or death. Results: The study sample was 58±12 years old, 72% male, and 63% Caucasian. Hemoglobin at implantation was 11±2 g/dL. Maximum LV recovery was seen a median of 103 (IQR 49-158) days after LVAD implantation. Improved LV function occurred in 25 (21%) patients, while LVEF remained stable or worsened in 94 (79%) of patients. When compared with patients whose LVEF remained stable or worsened, patients with improved LV function were more likely to be female (p=0.05). GIB occurred in 29 patients (24%). Improved LV function was associated with a significantly decreased risk of GIB (Figure; p=0.05). Conclusions: Improved LV function is seen in one-fourth of patients and is associated with a significantly decreased risk of GIB following CF-LVAD implantation.

Analysis of reported randomized trials of streptokinase therapy for acute myocardial infarction in the 1980s

Functional mitral regurgitation (MR) is a common finding in dilated cardiomyopathy. Left ventricular (LV) reverse remodeling with LV size reduction and improvement in LV function is a well recognized phenomenon. We aimed to evaluate the impact of LV remodeling on the mechanism leading to functional MR. Among 188 patients with non-ischemic dilated cardiomyopathy, 10 patients significantly improved their LV function, reduced LV size and MR severity during follow-up (RRMR). A comparison was made between their baseline and follow-up echocardiographic examinations and to a matched-control group of patients who did not improve (no RRMR). LV and left atrium (LA) dimensions and volumes, LV mass (LVM), LV ejection fraction (LVEF) (Simpsons), sphericity index (SI), mitral valve tenting area (TA) coaptation distance (CD), effective regurgitant orifice (ERO), and regurgitant volume were calculated. Multivariable analysis was performed in order to evaluate which echocardiographic parameters related to MR improvement in reverse remodeling. LV and LA dimensions and volumes, LVM, SI, TA, CD, ERO and right ventricle, in the RRMR group significantly decreased at follow-up (p < 0.04 for all). When compared to no RRMR, despite a similar ERO (0.2 ± 0.05 vs. 0.2 ± 0.08, p = 0.13) and a larger regurgitant volume (38 ± 9 vs. 29 ± 8 mL, p = 0.05) and despite similar clinical characteristics and medical treatment we found significantly higher LVEF, smaller LV dimensions and volumes, smaller LVM and SI in the RRMR group (p < 0.05 for all). On multivariable analysis the SI was the sole predictor of RRMR (p = 0.04, OR = 0.76, CI 0.58-0.99). Reverse remodeling characterized by improvement in LV function, reduction in LV size and an associated reduction in MR severity is related to LV SI at baseline.

Purpose: Aging exaggerates myocardial injury caused by sepsis and up-regulated the expression of cytokines. IL-37 is an anti-inflammatory cytokine, mice with transgenic expression of IL-37 are protected against endotoxic shock, exhibiting reduced lung and kidney damage. We tested the hypothesis that IL-37 protects the aging heart against endotoxemic cardiac depression via suppression of myocardial inflammatory responses. Methods: WT and IL-37 transgenic (tg) mice, males of adult (4-6 months) and aging (18-20 months), were treated with endotoxin (E. coli 011:B4; 0.5 mg/kg i.v.). Left ventricular (LV) function was measured with a pressure-volume microcatheter at 1-6 h after injection. Plasma and myocardial tissue homogenate were prepared for analysis of MCP-1, TNF-α and IL-1β by ELISA. Results: Endotoxin caused greater depression of LV function in WT aging mice, TNF-α and IL-1β in comparison to WT adult mice. Aging IL-37Tg mice had improved ejection fraction and cardiac output after LPS injection that were associated with lower myocardial levels of cytokines. To determine the role of MCP-1 in myocardial production of TNF-α and IL-1β, as well as in LV dysfunction, we treated WT aging mice with MCP-1-neutrlizing antibody and found that neutralization MCP-1 reduced myocardial TNF-α and IL-1β levels and improved LV function. Conclusions: Endotoxemia results in worse LV functional injury in aging WT mice. MCP-1 plays an important role in mediating the production of cardiac depressant cytokines and resultant LV dysfunction. IL-37 improves LV function in aging mice during endotoxemia through suppression of myocardial production of MCP-1 and cardiodepressant cytokines. Thus, IL-37 has the therapeutic potential for cardiac protection in the elderly against functional injury associated with major surgeries. ![Figure][1] Figure: Aging IL-37 Tg mice LV function [1]: pending:yes

The objective of the research is to investigate the role of very small embryonic-like stem cells (VSELs™), as well as CD34 + cells, in a study that will compare the efficacy of these two cell types for retinal repair.Licensing agreement: TiGenix & Sobi TiGenix (Belgium; www.tigenix.com)has licensed the marketing and distribution of ChondroCelect ® , the cell-based medicinal product for the repair of cartilage defects of the knee, to the international specialty healthcare company dedicated to rare diseases, Swedish Orphan Biovitrum AB (www.sobi.com).ChondroCelect was the first cellbased product to be approved in Europe.It is currently available for patients and reimbursed in Belgium, The Netherlands and Spain.Sales of ChondroCelect in 2013 were US$5.76 (EU€4.3)million, a growth of 25% on a like-for-like basis over 2012.Sobi will continue to market and distribute the product where it is currently available and has also acquired the exclusive rights to expand the product's availability to patients in multiple additional territories, including the rest of the EU, Norway, Switzerland, Turkey and Russia, plus the countries of the Middle East and North Africa.TiGenix will receive a royalty of 22% of the net sales of ChondroCelect in the first year of the agreement, and 20% of the net sales of ChondroCelect thereafter.There will be no upfront or milestone payments.The agreement took effect on June 1, 2014, and has a duration of 10 years. Launching new projects, products & servicesCatapult

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