Genetic determinants of responsiveness to mesenchymal stem cell injections in non-ischemic dilated cardiomyopathy.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness to MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial.

Methods: POSEIDON-DCM patients (n = 34) underwent genetic sequence analysis and deletion/duplication testing.

Alternative access for transcatheter aortic valve replacement in older adults: A collaborative study from France and United States.

Background: We examined the outcomes of older adults undergoing nontrans-femoral (non-TF) transcatheter aortic valve replacement (TAVR) procedures including trans-apical (TA), trans-aortic (TAo), trans-subclavian (TSub), and trans-carotid (TCa) techniques.

Methods And Results: This is an observational study of all consecutive older patients who underwent non-TF TAVR for symptomatic severe AS with Edwards Sapien (ES), Medtronic CoreValve, ES3 or Lotus Valve at three centers in France and the United States from 04/2008 to 02/2017. Baseline characteristics and clinical outcomes were defined according to VARC-2 criteria.

A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration.

Background: The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT).

Objectives: This study sought to test the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions.

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.

Methods: This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.

Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study).

Rationale: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure.

Objective: To compare the safety and efficacy of 2 doses of allogeneic bone marrow-derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy.

Methods And Results: Thirty patients with ischemic cardiomyopathy received in a blinded manner either 20 million (n=15) or 100 million (n=15) allogeneic human mesenchymal stem cells via transendocardial injection (0.

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

Background: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty.

Effects of Transendocardial Stem Cell Injection on Ventricular Proarrhythmia in Patients with Ischemic Cardiomyopathy: Results from the POSEIDON and TAC-HFT Trials.

Transendocardial stem cell injection in patients with ischemic cardiomyopathy (ICM) improves left ventricular function and structure but has ill-defined effects on ventricular arrhythmias. We hypothesized that mesenchymal stem cell (MSC) implantation is not proarrhythmic. Post hoc analyses were performed on ambulatory ECGs collected from the POSEIDON and TAC-HFT trials.

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial.

Background: Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM).

Objectives: The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM.

Methods: Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio.

Transient and persistent conduction abnormalities following transcatheter aortic valve replacement with the Edwards-Sapien prosthesis: a comparison between antegrade vs. retrograde approaches.

Background: Electrocardiographic conduction abnormalities following transcatheter aortic valve replacement (TAVR) with the Edwards-Sapien valve (ESV) are not uncommon and may be transient. We sought to examine the clinical time-course of conduction abnormalities after TAVR with ESV and determine risk factors for persistent abnormalities.

Methods: In this single-center prospective study, 116 consecutive patients underwent implantation of the ESV after approval by the Food and Drug Administration (FDA).

Elective or Emergency Use of Mechanical Circulatory Support Devices During Transcatheter Aortic Valve Replacement.

Objective: Evaluate the use of mechanical circulatory support (MCS) devices in high-risk patients undergoing transcatheter aortic valve replacement (TAVR).

Background: The use of MCS devices in elderly patients with multiple comorbidities undergoing TAVR is underexplored.

Methods: All patients undergoing TAVR at a single tertiary academic center who required MCS during index procedure between 2008 and 2015 were included in a prospective database.

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious.

Emergent Percutaneous Biventricular Support during Transcatheter Aortic Valve Replacement.

Coronary obstruction following transcatheter aortic valve replacement (TAVR) is a dreaded complication which occurs in less than 1% of the procedures. Temporary hemodynamic support may be required in cases of hemodynamic collapse while performing a high-risk percutaneous coronary intervention in these patients. A challenging case is described where emergent percutaneous biventricular support (Tandem Heart for right ventricular support and Impella CPTM for left ventricular support) was used as a bridge to recovery in a patient with coronary obstruction during TAVR with the Edwards SAPIEN prosthesis.

Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease.

An important stage in the development of any new therapeutic agent is establishment of the optimal dosage and route of administration. This can be particularly challenging when the treatment is a biologic agent that might exert its therapeutic effects via complex or poorly understood mechanisms. Multiple preclinical and clinical studies have shown paradoxical results, with inconsistent findings regarding the relationship between the cell dose and clinical benefit.

Synergistic Effects of Combined Cell Therapy for Chronic Ischemic Cardiomyopathy.

Background: Both bone marrow-derived mesenchymal stem cells (MSCs) and c-kit(+) cardiac stem cells (CSCs) improve left ventricular remodeling in porcine models and clinical trials. Using xenogeneic (human) cells in immunosuppressed animals with acute ischemic heart disease, we previously showed that these 2 cell types act synergistically.

Objectives: To more accurately model clinical applications for heart failure, this study tested whether the combination of autologous MSCs and CSCs produce greater improvement in cardiac performance than MSCs alone in a nonimmunosuppressed porcine model of chronic ischemic cardiomyopathy.

Combined Retrograde/Antegrade Approach to Transcatheter Closure of an Aortic Paravalvular Leak.

New interventional techniques have made transcatheter closure of aortic paravalvular leaks a viable therapeutic option to treat the sequelae of these defects, including congestive heart failure and hemolysis. We report the transcatheter closure of an aortic paravalvular leak via a combined retrograde/antegrade approach. This was necessary because of difficulty in crossing the defect with a sheath from the retrograde approach.

Prognostic value of serial B-type natriuretic peptide measurement in transcatheter aortic valve replacement (from the PARTNER Trial).

B-type natriuretic peptide (BNP) levels have shown a correlation with outcomes in studies of aortic valve surgery. Results from multicenter trials of BNP in transcatheter aortic valve surgery (TAVR) are lacking. The aim of this study was to investigate the prognostic role of serial measurement of BNP in transfemoral TAVR.

The story of the lost needle: Foreign body embolization to the heart.

A 61-year-old female was evaluated because of severe symptomatic mitral regurgitation. She was found to have a foreign body in the heart by cardiac catheterization. Through a retrospective review of serial imaging studies, we found that a hypodermic needle had been retained in the body from a prior abdominal wall surgery and had subsequently migrated to the heart.

Management of transcatheter aortic valve embolization into the left ventricle.

Embolization of transcatheter aortic valve replacement (TAVR) prostheses is a rare and serious procedural complication. While embolization into the aorta can sometimes be managed by transcatheter techniques, embolization into the left ventricle (LV) often requires immediate open heart surgery. We report three TAVR cases complicated by LV embolization.

Long-term outcomes associated with the transaortic approach to transcatheter Aortic valve replacement.

Objective: We investigated the long-term safety, efficacy and clinical outcomes associated with transaortic (TAO) transcatheter aortic valve replacement (TAVR) in the United States.

Background: We previously reported the technical feasibility and short-term safety of TAO TAVR. Compared to transapical (TAP) access, the TAO approach was associated with shorter median intensive care unit (ICU) length of stay (LOS) and more favorable technical learning curve.

Multimodality image guidance with Dyna-CT for transcatheter treatment of paravalvular leak of a stentless valve.

The transcatheter treatment of paravalvular leaks (PVL) are technically challenging procedures; they pose increasing difficulty in cases where there is a stentless valve, without the usual fluoroscopic landmarks. Hence, there is limited experience in treating this defect percutaneously. We present a case of a patient with an aortic PVL of a stentless valve and how the integrated use of multi-imaging modalities (transesophageal echocardiography, computed tomography and rotational angiography) allowed the demarcation of landmarks onto live fluoroscopy and guided the transcatheter occlusion of the PVL.

Rationale and design of the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy (the POSEIDON-DCM study): a phase I/II, randomized pilot study of the comparative safety and efficacy of transendocardial injection of autologous mesenchymal stem cell vs. allogeneic mesenchymal stem cells in patients with non-ischemic dilated cardiomyopathy.

While accumulating clinical trials have focused on the impact of cell therapy in patients with acute myocardial infarction (MI) and ischemic cardiomyopathy, there are fewer efforts to examine cell-based therapy in patients with non-ischemic cardiomyopathy (NICM). We hypothesized that cell therapy could have a similar impact in NICM. The POSEIDON-DCM trial is a phase I/II trial designed to address autologous vs.

Clinical outcomes with on-label and off-label use of the transcatheter heart valve in the United States.

Objective: We explored the efficacy, safety, and clinical consequences of on-label and off-label transcatheter aortic valve replacement (TAVR) in the real-world setting.

Background: The transcatheter heart valve (THV) was initially approved only for transfemoral (TF) delivery (on-label use) during TAVR in inoperable patients with severe aortic stenosis (AS). Because of lack of alternative options in TAVR-eligible patients with inadequate TF access, other routes have been utilized for THV implantation (off-label use), outcomes of which were previously unknown.

Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial.

Rationale: Although accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis.

Objective: To test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects.

New-onset atrial fibrillation after aortic valve replacement: comparison of transfemoral, transapical, transaortic, and surgical approaches.

Objectives: This study sought to determine the incidence of new-onset atrial fibrillation (AF) associated with different methods of isolated aortic valve replacement (AVR)-transfemoral (TF), transapical (TA), and transaortic (TAo) catheter-based valve replacement and conventional surgical approaches.

Background: The relative incidences of AF associated with the various access routes for AVR have not been well characterized.

Methods: In this single-center, retrospective cohort study, we evaluated a total of 231 consecutive patients who underwent AVR for degenerative aortic stenosis (AS) between March 2010 and September 2012.

Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial.

Rationale: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown.

Objective: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments.

Methods And Results: Biplane ventriculographic and endocardial tracings were recorded.