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The New England Journal of Medicine Dec 2017Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with...
BACKGROUND
Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia.
METHODS
We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter-defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging.
RESULTS
From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation "blanking period" (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year.
CONCLUSIONS
In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes-Jewish Hospital Foundation and others.).
Topics: Aged; Aged, 80 and over; Catheter Ablation; Cicatrix; Defibrillators, Implantable; Electrocardiography; Electrophysiologic Techniques, Cardiac; Fatal Outcome; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Radiosurgery; Stroke; Stroke Volume; Tachycardia, Ventricular; Tomography, X-Ray Computed
PubMed: 29236642
DOI: 10.1056/NEJMoa1613773 -
Progress in Biophysics and Molecular... Jan 2016Many cardiac electrophysiological abnormalities are accompanied by autonomic nervous system dysfunction. Here, we review mechanisms by which the cardiac nervous system... (Review)
Review
Many cardiac electrophysiological abnormalities are accompanied by autonomic nervous system dysfunction. Here, we review mechanisms by which the cardiac nervous system controls normal and abnormal excitability and may contribute to atrial and ventricular tachyarrhythmias. Moreover, we explore the potential antiarrhythmic and/or arrhythmogenic effects of modulating the autonomic nervous system by several strategies, including ganglionated plexi ablation, vagal and spinal cord stimulations, and renal sympathetic denervation as therapies for atrial and ventricular arrhythmias.
Topics: Animals; Heart Atria; Heart Diseases; Heart Ventricles; Humans; Nervous System Physiological Phenomena
PubMed: 26780507
DOI: 10.1016/j.pbiomolbio.2015.12.015 -
Cell Stem Cell Jan 2015Mesenchymal stem cells (MSCs) reside in the perivascular niche of many organs, including kidney, lung, liver, and heart, although their roles in these tissues are poorly...
Mesenchymal stem cells (MSCs) reside in the perivascular niche of many organs, including kidney, lung, liver, and heart, although their roles in these tissues are poorly understood. Here, we demonstrate that Gli1 marks perivascular MSC-like cells that substantially contribute to organ fibrosis. In vitro, Gli1(+) cells express typical MSC markers, exhibit trilineage differentiation capacity, and possess colony-forming activity, despite constituting a small fraction of the platelet-derived growth factor-β (PDGFRβ)(+) cell population. Genetic lineage tracing analysis demonstrates that tissue-resident, but not circulating, Gli1(+) cells proliferate after kidney, lung, liver, or heart injury to generate myofibroblasts. Genetic ablation of these cells substantially ameliorates kidney and heart fibrosis and preserves ejection fraction in a model of induced heart failure. These findings implicate perivascular Gli1(+) MSC-like cells as a major cellular origin of organ fibrosis and demonstrate that these cells may be a relevant therapeutic target to prevent solid organ dysfunction after injury.
Topics: Animals; Antigens; Aorta; Blood Vessels; Bone Marrow Cells; Cell Differentiation; Cell Lineage; Cells, Cultured; Colony-Forming Units Assay; Diphtheria Toxin; Endothelial Cells; Fibrosis; Heart Ventricles; Homeostasis; Humans; Kruppel-Like Transcription Factors; Mesenchymal Stem Cells; Mice; Myofibroblasts; Neovascularization, Physiologic; Organ Specificity; Pericytes; Proteoglycans; Receptor, Platelet-Derived Growth Factor beta; Stem Cell Niche; Zinc Finger Protein GLI1
PubMed: 25465115
DOI: 10.1016/j.stem.2014.11.004 -
Circulation Feb 2022Left ventricular noncompaction cardiomyopathy (LVNC) was discovered half a century ago as a cardiomyopathy with excessive trabeculation and a thin ventricular wall. In...
BACKGROUND
Left ventricular noncompaction cardiomyopathy (LVNC) was discovered half a century ago as a cardiomyopathy with excessive trabeculation and a thin ventricular wall. In the decades since, numerous studies have demonstrated that LVNC primarily has an effect on left ventricles (LVs) and is often associated with LV dilation and dysfunction. However, in part because of the lack of suitable mouse models that faithfully mirror the selective LV vulnerability in patients, mechanisms underlying the susceptibility of LVs to dilation and dysfunction in LVNC remain unknown. Genetic studies have revealed that deletions and mutations in (PR domain-containing 16) cause LVNC, but previous conditional knockout mouse models do not mirror the LVNC phenotype in patients, and the underlying molecular mechanisms by which PRDM16 deficiency causes LVNC are still unclear.
METHODS
cardiomyocyte-specific knockout () mice were generated and analyzed for cardiac phenotypes. RNA sequencing and chromatin immunoprecipitation deep sequencing were performed to identify direct transcriptional targets of PRDM16 in cardiomyocytes. Single-cell RNA sequencing in combination with spatial transcriptomics was used to determine cardiomyocyte identity at the single-cell level.
RESULTS
Cardiomyocyte-specific ablation of in mice caused LV-specific dilation and dysfunction, as well as biventricular noncompaction, which fully recapitulated LVNC in patients. PRDM16 functioned mechanistically as a compact myocardium-enriched transcription factor that activated compact myocardial genes while repressing trabecular myocardial genes in LV compact myocardium. Consequently, LV compact myocardial cardiomyocytes shifted from their normal transcriptomic identity to a transcriptional signature resembling trabecular myocardial cardiomyocytes or neurons. Chamber-specific transcriptional regulation by PRDM16 was attributable in part to its cooperation with LV-enriched transcription factors Tbx5 and Hand1.
CONCLUSIONS
These results demonstrate that disruption of proper specification of compact cardiomyocytes may play a key role in the pathogenesis of LVNC. They also shed light on underlying mechanisms of the LV-restricted transcriptional program governing LV chamber growth and maturation, providing a tangible explanation for the susceptibility of LV in a subset of LVNC cardiomyopathies.
Topics: Animals; DNA-Binding Proteins; Heart Ventricles; Mice; Mice, Knockout; Myocardium; Myocytes, Cardiac; Transcription Factors
PubMed: 34915728
DOI: 10.1161/CIRCULATIONAHA.121.056666 -
Clinical Medicine (London, England) Sep 2023Ventricular tachycardia (VT) describes rapid heart rhythms originating from the ventricles. Accurate diagnosis of VT is important to allow prompt referral to specialist... (Review)
Review
Ventricular tachycardia (VT) describes rapid heart rhythms originating from the ventricles. Accurate diagnosis of VT is important to allow prompt referral to specialist services for ongoing management. The diagnosis of VT is usually made based on electrocardiographic data, most commonly 12-lead echocardiography (ECG), as well as supportive cardiac telemetric monitoring. Distinguishing between VT and supraventricular arrhythmias on ECG can be difficult. However, the VT diagnosis frequently needs to be made rapidly in the acute setting. In this review, we discuss the definition of VT, review features of wide-complex tachycardia (WCT) on ECG that might be helpful in diagnosing VT, discuss the different substrates in which VT can occur and offer brief comments on management considerations for patients found to have VT.
Topics: Humans; Tachycardia, Supraventricular; Diagnosis, Differential; Tachycardia, Ventricular; Heart Ventricles; Electrocardiography
PubMed: 37775174
DOI: 10.7861/clinmed.2023-23.5.Cardio3 -
Europace : European Pacing,... Dec 2018
Topics: Animals; Arrhythmias, Cardiac; Atrial Remodeling; Dogs; Heart Ventricles; Myocardial Infarction; Neurons
PubMed: 29931207
DOI: 10.1093/europace/euy134 -
JACC. Clinical Electrophysiology Dec 2022
Topics: Humans; Papillary Muscles; Heart Ventricles; Mitral Valve Insufficiency
PubMed: 36543497
DOI: 10.1016/j.jacep.2022.08.030 -
Transactions of the American Clinical... 2009Ventricular tachycardia (VT) is a life-threatening arrhythmia that is common to all forms of heart disease and an important cause of sudden death. Ventricular scars from... (Review)
Review
Ventricular tachycardia (VT) is a life-threatening arrhythmia that is common to all forms of heart disease and an important cause of sudden death. Ventricular scars from infarction or replacement fibrosis provide a substrate for reentry that is a common cause. Understanding the pathophysiologic link between ventricular scars and ventricular tachycardia informs approaches to identify patients at risk, has led to development of methods to ablate the arrhythmia substrate that can be applied even in severe heart disease, and suggests future diagnostic and therapeutic strategies.
Topics: Catheter Ablation; Cicatrix; Defibrillators, Implantable; Electrophysiological Phenomena; Heart Ventricles; Humans; Risk Factors; Tachycardia, Ventricular
PubMed: 19768192
DOI: No ID Found -
JACC. Clinical Electrophysiology Feb 2023Frequent premature ventricular complexes (PVCs) can result in a reversible form of cardiomyopathy that usually affects the left ventricle (LV).
BACKGROUND
Frequent premature ventricular complexes (PVCs) can result in a reversible form of cardiomyopathy that usually affects the left ventricle (LV).
OBJECTIVES
The objective of this study was to assess whether frequent PVCs have an impact on right ventricular (RV) function.
METHODS
Serial cardiac magnetic resonance (CMR) studies were performed in a series of 47 patients before and after ablation of frequent PVCs.
RESULTS
Patients with RV cardiomyopathy (ejection fraction [EF] <0.45) had more frequent PVCs than did patients without decreased RV function (23% ± 11% vs 15% ± 11%, P = 0.03). Likewise, patients with LV cardiomyopathy (EF <0.50) had more frequent PVCs than did patients without decreased LV function (23% ± 10% vs 14% ± 12%, P = 0.003). LV dysfunction was present in 21 patients (45%). In patients with LV dysfunction, 15 patients (32%) had biventricular dysfunction, and 6 patients (13%) had isolated LV dysfunction. A total of 19 patients (40%) had RV dysfunction, and 4 of the patients with RV dysfunction (9%) had isolated RV dysfunction. Cardiac magnetic resonance was repeated 1.9 ± 1.3 years after ablation. In patients with successful ablation, RV function improved, and in patients without successful ablation, RV function did not significantly change (before and after ablation RVEF 0.45 ± 0.09 and 0.52 ± 0.09; P < 0.001 vs. 0.46 ± 0.07 and 0.48 ± 0.04; P = 0.14, respectively).
CONCLUSIONS
Frequent PVCs can cause RV cardiomyopathy that parallels LV cardiomyopathy and is reversible with successful ablation.
Topics: Humans; Heart; Heart Ventricles; Ventricular Premature Complexes; Ventricular Dysfunction, Right; Ventricular Dysfunction, Left
PubMed: 36858685
DOI: 10.1016/j.jacep.2022.09.016 -
European Journal of Pharmacology Aug 2018Heart failure (HF) is a clinical syndrome characterized by ventricular contractile dysfunction. About 50% of death in patients with HF are due to fetal ventricular... (Review)
Review
Heart failure (HF) is a clinical syndrome characterized by ventricular contractile dysfunction. About 50% of death in patients with HF are due to fetal ventricular arrhythmias including ventricular tachycardia and ventricular fibrillation. Understanding ventricular arrhythmic substrates and discovering effective antiarrhythmic interventions are extremely important for improving the prognosis of patients with HF and reducing its mortality. In this review, we discussed ventricular arrhythmic substrates and current clinical therapeutics for ventricular arrhythmias in HF. Base on the fact that classic antiarrhythmic drugs have the limited efficacy, side effects, and proarrhythmic potentials, we also updated some therapeutic strategies for the development of potential new antiarrhythmic interventions for patients with HF.
Topics: Anti-Arrhythmia Agents; Heart Conduction System; Heart Failure; Heart Ventricles; Humans; Myocytes, Cardiac; Prognosis; Tachycardia, Ventricular; Treatment Outcome; Ventricular Fibrillation
PubMed: 29940156
DOI: 10.1016/j.ejphar.2018.06.024