ABSTRACT
BACKGROUND: Left ventricular (LV) endocardial pacing is a promising method to deliver cardiac resynchronization therapy (CRT). WiSE-CRT is a wireless LV endocardial pacing system, and delivers ultrasonic energy to an LV electrode. OBJECTIVE: The purpose of this study was to present short-term outcomes with the WiSE-CRT system in centers with no prior implanting experience. METHODS: Data were prospectively collected from 19 centers where WiSE-CRT systems were implanted during the roll-in phase of the SOLVE-CRT trial. Patients were followed at 1, 3, and 6 months, including transthoracic echo (TTE) at 6 months. RESULTS: The WiSE-CRT was successfully implanted in all 31 attempted cases, and 30 patients completed the 6-month follow-up. One patient underwent heart transplantation 1 month after implantation, and was excluded. Fourteen (46.7%) patients demonstrated ≥1 NYHA class improvement. TTE data were available in 29 patients. LV ejection fraction, LV end-systolic volume, and LV end-diastolic volume improved from 28.3% ± 6.7% to 33.5% ± 6.9% (P < .001), 134.9 ± 51.3 mL to 111.1 ± 40.3 mL (P = .0004), and 185.4 ± 58.8 mL to 164.9 ± 50.6 mL (P = .0017), respectively. There were 3 (9.7%) device-related type 1 complications: 1 insufficient LV pacing, 1 embolization of an unanchored LV electrode, and 1 skin infection. CONCLUSIONS: We demonstrated a high success rate of LV endocardial electrode placement in centers with no prior implanting experience. Favorable clinical responses in heart failure symptoms and significant LV reverse remodeling were noted.
Subject(s)
Cardiac Resynchronization Therapy Devices , Cardiac Resynchronization Therapy/methods , Heart Failure/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Prosthesis DesignSubject(s)
Adult Stem Cells/physiology , Antigens, Ly/metabolism , Membrane Proteins/metabolism , Myocardial Infarction/physiopathology , Myocytes, Cardiac/physiology , Animals , Antigens, Ly/genetics , Cell Differentiation , Cell Lineage , Cells, Cultured , Coronary Vessels/surgery , Disease Models, Animal , Green Fluorescent Proteins/genetics , Humans , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Transgenic , Muscle Development , Stem Cell TransplantationABSTRACT
Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
Subject(s)
Embryonic Stem Cells/physiology , Heart/physiology , Tissue Engineering , Action Potentials , Animals , Antigens, Differentiation/genetics , Antigens, Differentiation/metabolism , Calcium Signaling , Cell Differentiation , Cell Shape , Cells, Cultured , Embryonic Stem Cells/metabolism , Epigenesis, Genetic , Genotype , Histocompatibility/genetics , Histocompatibility Antigens Class II/genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, SCID , Myocardial Contraction , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/physiology , Organ Culture Techniques , Organoids/transplantation , Parthenogenesis , Phenotype , Stem Cell Transplantation , Transplantation, HomologousSubject(s)
Arrhythmias, Cardiac/etiology , Cardiomyopathies/therapy , Defibrillators, Implantable/adverse effects , Electrocardiography , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/etiology , Adult , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/therapy , Cardiomyopathies/diagnosis , Follow-Up Studies , Humans , Male , Monitoring, Physiologic/methods , Pacemaker, Artificial/adverse effects , Recurrence , Severity of Illness IndexSubject(s)
Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/diagnosis , Myotonic Dystrophy , Sodium Channel Blockers/adverse effects , Adult , Arrhythmias, Cardiac/complications , Humans , Male , Myotonic Dystrophy/classification , Myotonic Dystrophy/complications , Myotonic Dystrophy/drug therapy , Sodium Channels/physiologyABSTRACT
Despite the increasing number of sophisticated, computerized tools available to the practicing electrophysiologist for facilitating catheter ablation of ventricular tachycardia, the procedure is often quite challenging. Use of these tools needs to be kept in perspective, subservient to the judgment of the physician. This review explores a series of principles that should be applied in these procedures.
Subject(s)
Catheter Ablation/methods , Tachycardia, Ventricular/surgery , Cardiac Pacing, Artificial , Catheter Ablation/standards , Clinical Competence , Humans , Imaging, Three-Dimensional/methods , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/pathologyABSTRACT
Two-photon excitation microscopy has become the standard technique for high resolution deep tissue and intravital imaging. It provides intrinsic three-dimensional resolution in combination with increased penetration depth compared to single-photon confocal microscopy. This article will describe the basic physical principles of two-photon excitation and will review its multiple applications to cardiovascular imaging, including second harmonic generation and fluorescence laser scanning microscopy. In particular, the capability and limitations of multiphoton microscopy to assess functional heterogeneity on a cellular scale deep within intact, Langendorff-perfused hearts are demonstrated. It will also discuss the use of two-photon excitation-induced release of caged compounds for the study of intracellular calcium signaling and intercellular dye transfer.
Subject(s)
Cardiovascular System/cytology , Microscopy, Fluorescence, Multiphoton , Animals , Cardiovascular System/chemistry , Cardiovascular System/metabolism , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Humans , Photolysis , Signal TransductionABSTRACT
The cardiomyogenic potential of adult bone marrow (BM) cells after being directly transplanted into the ischemically injured heart remains a controversial issue. In this study, we investigated the ability of transplanted BM cells to develop intracellular calcium ([Ca(2+)](i)) transients in response to membrane depolarization in situ. Low-density mononuclear (LDM) BM cells, c-kit-enriched (c-kit(enr)) BM cells, and highly enriched lin(-) c-kit(+) BM cells were obtained from adult transgenic mice ubiquitously expressing enhanced green fluorescent protein (EGFP), and injected into peri-infarct myocardiums of nontransgenic mice. After 9-10 days the mice were killed, and the hearts were removed, perfused in Langendorff mode, loaded with the calcium-sensitive fluorophore rhod-2, and subjected to two-photon laser scanning fluorescence microscopy (TPLSM) to monitor action potential-induced [Ca(2+)](i) transients in EGFP-expressing donor-derived cells and non-expressing host cardiomyocytes. Whereas spontaneous and electrically evoked [Ca(2+)](i) transients were found to occur synchronously in host cardiomyocytes along the graft-host border and in areas remote from the infarct, they were absent in all of the >3,000 imaged BM-derived cells that were located in clusters throughout the infarct scar or peri-infarct zone. We conclude that engrafted BM-derived cells lack attributes of functioning cardiomyocytes, calling into question the concept that adult BM cells can give rise to substantive cardiomyocyte regeneration within the infarcted heart.
