Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Cardiosphere-derived cells (CDCs) ameliorate skeletal and cardiac muscle deterioration in experimental models of Duchenne muscular dystrophy. The HOPE-2 trial examined the safety and efficacy of sequential intravenous infusions of human allogeneic CDCs in late-stage Duchenne muscular dystrophy.

Methods: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients with Duchenne muscular dystrophy, aged 10 years or older with moderate upper limb impairment, were enrolled at seven centres in the USA.

Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.

Background: Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events.

Current state of cardiac troponin testing in Duchenne muscular dystrophy cardiomyopathy: review and recommendations from the Parent Project Muscular Dystrophy expert panel.

Cardiac disease is now the leading cause of death in Duchenne muscular dystrophy (DMD). Clinical evaluations over time have demonstrated asymptomatic cardiac troponin elevations and acute elevations are associated with symptoms and cardiac dysfunction in DMD. Clinicians require a better understanding of the relationship of symptoms, troponin levels and progression of cardiac disease in DMD.

Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial.

Aims: Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial.

Methods And Results: We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI).

Allogeneic cardiosphere-derived cells for the treatment of heart failure with reduced ejection fraction: the Dilated cardiomYopathy iNtervention with Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial.

Aims: The DYNAMIC trial assessed the safety and explored the efficacy of multivessel intracoronary infusion of allogeneic cardiosphere-derived cells (CDCs) in patients with heart failure and reduced ejection fraction (HFrEF). Here we report the results of the DYNAMIC trial.

Methods And Results: We enrolled 14 patients with EF ≤35% and NYHA Class III-IV despite maximal medical and device-based therapy in this single-centre, open-label trial.

Combining Stem Cell Therapy for Advanced Heart Failure and Ventricular Assist Devices: A Review.

The use of stem cell therapy in combination with a left ventricular assist device (LVAD) for patients with advanced heart failure (HF) is an attractive concept with the potential to alter the natural history of HF. Cell therapy trials for HF have demonstrated excellent safety and encouraging results, but current rates of myocardial recovery after LVAD implantation are limited. Early trials combining these 2 therapies to increase the likelihood of recovery and to potentially obviate the need for subsequent transplantation appear promising.

The Relationship Between Psychological Symptoms and Ventricular Assist Device Implantation.

Context: Ventricular assist devices (VADs) improve quality of life in advanced heart failure patients, but there are little data exploring psychological symptoms in this population.

Objective: This study examined the prevalence of psychiatric symptoms and disease over time in VAD patients.

Methods: This prospective multicenter cohort study enrolled patients immediately before or after VAD implant and followed them up to 48 weeks.

Impact of Left Ventricular to Mitral Valve Ring Mismatch on Recurrent Ischemic Mitral Regurgitation After Ring Annuloplasty.

Background: In ischemic mitral regurgitation (IMR), ring annuloplasty is associated with a significant rate of recurrent MR. Ring size is based on intertrigonal distance without consideration of left ventricular (LV) size. However, LV size is an important determinant of mitral valve (MV) leaflet tethering before and after repair.

Pain and Functional Status in Patients With Ventricular Assist Devices.

Context: Ventricular assist devices (VADs) have been shown to improve survival and overall quality of life, but there are limited data on pain control and functional status in this patient population.

Objectives: This study examined changes in pain, functional status, and quality of life over time in VAD patients.

Methods: Patients were enrolled in this prospective cohort study before or as early after VAD implant as possible and then followed for up to 48 weeks.

ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) Trial: Rationale and Design.

Autologous cardiosphere-derived cells (CDCs) were the first therapeutic modality to demonstrate myocardial regeneration with a decrease in scar size and an increase in viable, functional tissue. Widespread applicability of autologous CDC therapy is limited by the need for patient-specific myocardial biopsy, cell processing, and quality control, resulting in delays to therapy and inherent logistical and economic constraints. Preclinical data had demonstrated equivalent efficiency of allogeneic to autologous CDCs.

Hybrid Coronary Revascularization for the Treatment of Multivessel Coronary Artery Disease: A Multicenter Observational Study.

Background: Hybrid coronary revascularization (HCR) combines minimally invasive surgical coronary artery bypass grafting of the left anterior descending artery with percutaneous coronary intervention (PCI) of non-left anterior descending vessels. HCR is increasingly used to treat multivessel coronary artery disease that includes stenoses in the proximal left anterior descending artery and at least 1 other vessel, but its effectiveness has not been rigorously evaluated.

Objectives: This National Institutes of Health-funded, multicenter, observational study was conducted to explore the characteristics and outcomes of patients undergoing clinically indicated HCR and multivessel PCI for hybrid-eligible coronary artery disease, to inform the design of a confirmatory comparative effectiveness trial.

Surgical ablation of atrial fibrillation during mitral-valve surgery.

Background: Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited.

Methods: We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation.

Usability and feasibility of a tablet-based Decision-Support and Integrated Record-keeping (DESIRE) tool in the nurse management of hypertension in rural western Kenya.

Background: Mobile health (mHealth) applications have recently proliferated, especially in low- and middle-income countries, complementing task-redistribution strategies with clinical decision support. Relatively few studies address usability and feasibility issues that may impact success or failure of implementation, and few have been conducted for non-communicable diseases such as hypertension.

Objective: To conduct iterative usability and feasibility testing of a tablet-based Decision Support and Integrated Record-keeping (DESIRE) tool, a technology intended to assist rural clinicians taking care of hypertension patients at the community level in a resource-limited setting in western Kenya.

Surgical treatment of moderate ischemic mitral regurgitation.

Background: Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain.

Methods: We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair (combined procedure).

Management practices and major infections after cardiac surgery.

Background: Infections are the most common noncardiac complication after cardiac surgery, but their incidence across a broad range of operations, as well as the management factors that shape infection risk, remain unknown.

Objectives: This study sought to prospectively examine the frequency of post-operative infections and associated mortality, and modifiable management practices predictive of infections within 65 days from cardiac surgery.

Methods: This study enrolled 5,158 patients and analyzed independently adjudicated infections using a competing risk model (with death as the competing event).

Impact of socioeconomic status measures on hospital profiling in New York City.

Background: Current 30-day readmission models used by the Center for Medicare and Medicaid Services for the purpose of hospital-level comparisons lack measures of socioeconomic status (SES). We examined whether the inclusion of an SES measure in 30-day congestive heart failure readmission models changed hospital risk-standardized readmission rates in New York City (NYC) hospitals.

Methods And Results: Using a Centers for Medicare & Medicaid Services (CMS)-like model, we estimated 30-day hospital-level risk-standardized readmission rates by adjusting for age, sex, and comorbid conditions.

Changing the research landscape: the New York City Clinical Data Research Network.

The New York City Clinical Data Research Network (NYC-CDRN), funded by the Patient-Centered Outcomes Research Institute (PCORI), brings together 22 organizations including seven independent health systems to enable patient-centered clinical research, support a national network, and facilitate learning healthcare systems. The NYC-CDRN includes a robust, collaborative governance and organizational infrastructure, which takes advantage of its participants' experience, expertise, and history of collaboration. The technical design will employ an information model to document and manage the collection and transformation of clinical data, local institutional staging areas to transform and validate data, a centralized data processing facility to aggregate and share data, and use of common standards and tools.

Nurse management of hypertension in rural western Kenya: implementation research to optimize delivery.

Background: Hypertension is the leading global risk factor for mortality. Hypertension treatment and control rates are low worldwide, and insufficient human resource capacity is among the contributing factors. Thus, a critical component of hypertension management is to develop novel and effective solutions to the human resources challenge.

Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices.

Background: Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy.

Methods And Results: In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation.

Asymmetric versus symmetric tethering patterns in ischemic mitral regurgitation: geometric differences from three-dimensional transesophageal echocardiography.

Background: Ischemic mitral regurgitation (IMR) results from mitral leaflet tethering from left ventricular remodeling. Heterogeneity in local or global left ventricular remodeling can result in differential tethering patterns and affect mitral valve function and the degree of mitral regurgitation. The aims of this study were to compare mitral valve geometry in asymmetric and symmetric tethering patterns using three-dimensional transesophageal echocardiography and to examine the impact of tethering pattern on IMR severity.

Dynamics of device innovation: implications for assessing value.

Background: In recent years, there has been growing interest in evaluating the health and economic impact of medical devices. Payers increasingly rely on cost-effectiveness analyses in making their coverage decisions, and are adopting value-based purchasing initiatives. These analytic approaches, however, have been shaped heavily by their use in the pharmaceutical realm, and are ill-adapted to the medical device context.