Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure.

Background: Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF).

Objectives: This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF.

Methods: This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies.

A Path Forward for Regenerative Medicine.

Although clinical trials of cell-based approaches to cardiovascular disease have yielded some promising results, no cell-based therapy has achieved regulatory approval for a cardiovascular indication. To broadly assess the challenges to regulatory approval and identify strategies to facilitate this goal, the Cardiac Safety Research Consortium sponsored a session during the Texas Heart Institute International Symposium on Cardiovascular Regenerative Medicine in September 2017. This session convened leaders in cardiovascular regenerative medicine, including participants from academia, the pharmaceutical industry, the US Food and Drug Administration, and the Cardiac Safety Research Consortium, with particular focus on treatments closest to regulatory approval.

Evolution of Left Ventricular Assist Device Therapy for Advanced Heart Failure: A Review.

Importance: The mortality rate for the most advanced forms of heart failure with medical therapy alone remains unacceptably high at 30% to 80% at 1 year. In the past decade, left ventricular assist devices have assumed an increasingly prominent role in the management of these patients. This review included all English-language articles published over the past 15 years on left ventricular assist devices.

Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT(®) (Refractory Angina Cell Therapy) Clinical Update and Cost-Effective Analysis.

Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT(®) phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT's clinical update, assessing long-term sustained efficacy.

Human Umbilical Cord Blood for Transplantation Therapy in Myocardial Infarction.

Cell-based therapy is a promising therapy for myocardial infarction. Endogenous repair of the heart muscle after myocardial infarction is a challenge because adult cardiomyocytes have a limited capacity to proliferate and replace damaged cells. Pre-clinical and clinical evidence has shown that cell based therapy may promote revascularization and replacement of damaged myocytes after myocardial infarction.

Patient selection for ventricular assist devices: a moving target.

The number of patients with advanced heart failure that has become unresponsive to conventional medical therapy is increasing rapidly. One of the most promising new alternatives to heart transplantation is use of ventricular assist devices (VADs). To date, there are no guidelines for appropriate selection for use of these devices that are approved by national societies in the field.

Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.

Background: Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes.

Methods And Results: We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation.

Risk assessment for continuous flow left ventricular assist devices: does the destination therapy risk score work? An analysis of over 1,000 patients.

Objectives: This study sought to assess the utility of the Destination Therapy Risk Score (DTRS) in patients with continuous flow left ventricular assist devices (LVAD).

Background: The DTRS was developed to predict the risk of 90-day in-hospital mortality with pulsatile flow LVAD as destination therapy (DT). Despite ongoing use in patients with continuous flow devices, its utility has not been studied in such populations.

Clinical, molecular, and genomic changes in response to a left ventricular assist device.

The use of left ventricular assist devices in treating patients with end-stage heart failure has increased significantly in recent years, both as a bridge to transplantation and as destination therapy in those who are ineligible for cardiac transplantation. This increase is based largely on the results of several recently completed clinical trials with the new second-generation continuous-flow devices that showed significant improvements in survival, functional capacity, and quality of life. Additional information on the use of the first- and second-generation left ventricular assist devices has come from a recently released report spanning the years 2006 to 2009, from the Interagency Registry for Mechanically Assisted Circulatory Support, a National Heart, Lung, and Blood Institute-sponsored collaboration between the U.

Chronic treatment with clenbuterol modulates endothelial progenitor cells and circulating factors in a murine model of cardiomyopathy.

The purpose of this study was to determine the effects of chronic treatment with the beta 2 adrenergic receptor agonist clenbuterol on endothelial progenitor cells (EPC) in a well-characterized model of heart failure, the muscle LIM protein knockout (MLP(-/-)) mouse. MLP(-/-) mice were treated daily with clenbuterol (2 mg/kg) or saline subcutaneously for 6 weeks. Clenbuterol led to a 30% increase in CD31(+) cells in the bone marrow of MLP(-/-) heart failure mice (p < 0.

Recommendations for successful training on methods of delivery of biologics for cardiac regeneration: a report of the International Society for Cardiovascular Translational Research.

The field of myocardial regeneration (angiogenesis and myogenesis) might prove to play an important role in the future management of cardiovascular disease. Stem cells are currently undergoing testing in Phase I and Phase II clinical trials. Methods of delivery will affect the outcome of such therapies, perhaps significantly.

Clinical management of continuous-flow left ventricular assist devices in advanced heart failure.

Continuous-flow left ventricular assist devices (LVAD) have emerged as the standard of care for advanced heart failure patients requiring long-term mechanical circulatory support. Evidence-based clinical management of LVAD-supported patients is becoming increasingly important for optimizing outcomes. In this state-of-art review, we propose key elements in managing patients supported with the new continuous-flow LVADs.

Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes.

Objective: The aim of this study was to evaluate the incidence, risk factors, and effect on outcomes of right ventricular failure in a large population of patients implanted with continuous-flow left ventricular assist devices.

Methods: Patients (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec, Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the occurrence of right ventricular failure. Right ventricular failure was defined as requiring a right ventricular assist device, 14 or more days of inotropic support after implantation, and/or inotropic support starting more than 14 days after implantation.

Contemporary use of ventricular assist devices.

The introduction of the heart lung machine more than 50 years ago proved in principle that heart function can be replaced, albeit for short periods. This was followed by attempts to produce total or partial artificial hearts that could function for prolonged periods of time. Progress in this field has been intermittent but has accelerated considerably in the past 10 years, with ventricular assist devices (VADs) reaching an impressive degree of sophistication and complexity owing to the contributions from clinicians, engineers, scientists, industrialists, and others.

Sex and age dimorphism of myocardial gene expression in nonischemic human heart failure.

Background: We report the first comprehensive analysis of gene expression differences by sex and age in left ventricular samples from 102 patients with dilated cardiomyopathy.

Methods And Results: Gene expression data (HG-U133A gene chip, Affymetrix) were analyzed from 30 females and 72 males from 3 separate centers. More than 1800 genes displayed sexual dimorphism in the heart (adjusted P value <0.

Impact of center volume on outcomes of left ventricular assist device implantation as destination therapy: analysis of the Thoratec HeartMate Registry, 1998 to 2005.

Background: More than 400 patients with end-stage heart failure underwent left ventricular assist device (LVAD) implantation of LVAD as destination therapy (DT) after the US Food and Drug Administration approval of DT in 2002. Because most of these patients had surgeries at hospitals that were newly accredited, we sought to examine the impact of LVAD center volume on the outcomes of DT.

Methods And Results: From July 1998 through December 2005, a total of 377 patients underwent implantation of HeartMate I LVAD as DT at 68 centers in the United States.