Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients With Peripheral Artery Disease (STOP-PAD) Trial: Six-Month Results.

To present the 6-month results of the tromal Cell-Derived Factor-1 Plasmid reatment fr atients with eripheral rtery isease (STOP-PAD) trial. The trial was an attempt to alter the course of chronic limb-threatening ischemia (CLTI) with a biological agent vs placebo after successful arterial revascularization at or below the knee. The multicenter, randomized, double-blinded, placebo-controlled, phase 2B STOP-PAD trial ( identifier NCT02544204) randomized 109 patients (mean age 71 years; 68 men) with Rutherford category 5 or 6 CLTI and evidence of persistent impaired forefoot perfusion following recent successful revascularization to 8- (n=34) or 16-mg (n=36) intramuscular injections of a non-viral DNA plasmid-based treatment vs placebo (n=34).

SDF-1 plasmid treatment for patients with peripheral artery disease (STOP-PAD): Randomized, double-blind, placebo-controlled clinical trial.

The efficacy of biologic therapies in critical limb ischemia (CLI) remains elusive, in part, due to limitations in trial design and patient selection. Using a novel design, we examined the impact of complementing revascularization therapy with intramuscular JVS-100 - a non-viral gene therapy that activates endogenous regenerative repair pathways. In this double-blind, placebo-controlled, Phase 2B trial, we randomized 109 patients with CLI (Rutherford class V or VI) to 8 mg or 16 mg intramuscular injections of placebo versus JVS-100.

Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized Phase II trial.

Background: Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF).

Methods: Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections.

An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure.

Rationale: Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1.

Objective: We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters.

Effect of peri-infarct pacing early after myocardial infarction: results of the prevention of myocardial enlargement and dilatation post myocardial infarction study.

Background: Left ventricular (LV) remodeling has been attributed to the segmental loss of viable myocardium due to myocardial infarction (MI), which results in redistribution of cardiac workload, with increased regional wall stress in and around the infarct zone. Because ventricular pacing has been shown to reduce regional wall stress and workload in regions near the pacing site, this trial was designed to test whether chronic pacing near the infarct attenuates LV remodeling.

Methods And Results: Eighty patients with an anterior MI, peak creatine kinase >2000 mU/mL, ejection fraction ≤35%, wall motion abnormality (WMA) in >5 of 16 segments, and QRS <120 ms, were randomized to either control (implantable cardioverter-defibrillator [ICD]) or biventricular pacing with peri-infarct LV lead placement (cardiac resynchronization therapy [CRT]-D) arms between 2 and 14 days after the MI.

Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing.

Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics.

Ventricular preexcitation modulates strain and attenuates cardiac remodeling in a swine model of myocardial infarction.

Background: Myocardial infarction modifies the distribution of stress within the heart, increasing wall stress in ischemic and surrounding tissue, which often leads to adverse left ventricular remodeling. Electrical preexcitation pacing with appropriate timing of high-stress regions can reduce local strain and may attenuate global remodeling.

Methods And Results: Myocardial infarction was induced in 24 swine to study the short-term (n=12) and long-term (n=12) effects of therapy.

Feasibility of biventricular pacing in patients with recent myocardial infarction: impact on ventricular remodeling.

To test the hypothesis that biventricular pacing after a myocardial infarction with reduced ejection fraction can attenuate left ventricular (LV) remodeling, the authors studied 18 patients (myocardial infarction within 30-45 days, ejection fraction View Article and Find Full Text PDF

Early revascularization and ACC/AHA guideline-compliant medical management improve left ventricular function and short-term prognosis in patients presenting with acute myocardial infarction and severe left ventricular dysfunction.

Background: Myocardial infarction (MI) complicated by severe left ventricular (LV) dysfunction is associated with significant morbidity and mortality. The natural history of this population with contemporary revascularization and guideline-based medical therapies is poorly defined. We sought to determine the impact of contemporary treatment strategies on LV function and prognosis in patients with MI and severe LV dysfunction.

Importance of spatiotemporal heterogeneity of cellular restitution in mechanism of arrhythmogenic discordant alternans.

Background: Spatially discordant cellular alternans form a substrate for development of unidirectional block and ventricular fibrillation. However, the mechanisms responsible for discordant alternans remain poorly understood. Previous work suggests electrical restitution is critical to the development of alternans in single cells.

Area of left ventricular regional conduction delay and preserved myocardium predict responses to cardiac resynchronization therapy.

Unlabelled: Cardiac resynchronization therapy.

Background: A significant proportion of patients with dilated cardiomyopathy and left bundle branch block (LBBB) do not respond to cardiac resynchronization therapy (CRT). The purpose of this study was to investigate whether the electromechanical properties of the myocardium would predict acute hemodynamic improvement during left ventricular (LV) pacing.

Functional impact of rate irregularity in patients with heart failure and atrial fibrillation receiving cardiac resynchronization therapy.

Aims: Atrial fibrillation (AFib) with a rapid ventricular response may adversely impact cardiac performance, especially in patients with heart failure. However, it remains uncertain whether rhythm irregularity per se has unfavourable effects apart from tachycardia, and whether rate regularization alone can improve heart function.

Methods And Results: Nine subjects with chronic AFib, atrioventricular nodal block, and symptomatic heart failure (ejection fraction 14-30%) were studied using a pressure-volume catheter.

Left ventricular resynchronization therapy in a canine model of left bundle branch block.

Positive responses to left (LV) and biventricular (BV) stimulation observed in heart failure patients with left bundle branch block (LBBB) suggest a possible mechanism of LV resynchronization. An anesthetized canine LBBB model was developed using radio frequency ablation. Before and after ablation, LV pressure derivative over time (dP/dt) and aortic pulse pressure (PP) were assessed during normal sinus rhythm with right ventricle (RV), LV, or BV stimulation combined with four atrioventricular delays in six dogs.