-
JACC. Clinical Electrophysiology Dec 2019Although implantable cardioverter-defibrillators positively affect survival in patients at increased risk for arrhythmic sudden cardiac death, quality of life can be... (Review)
Review
Although implantable cardioverter-defibrillators positively affect survival in patients at increased risk for arrhythmic sudden cardiac death, quality of life can be negatively affected by recurrent therapies. Ventricular tachycardia (VT) ablation targets clinical arrhythmias to prevent recurrence. Although treatment of VT initially required open heart surgery, it has since been replaced by percutaneous ablation, a safe and effective catheter-based therapy to ablate myocardium from either the endocardial or the epicardial surface. Four basic mapping techniques are used to guide VT ablation: activation, entrainment, and pace and substrate mapping. Current recommendations for VT ablation, especially in the setting of structural heart disease, mostly reserve this treatment for patients for whom antiarrhythmic therapy has failed or is not tolerated or desired. These recommendations derive from multiple observational reports and several randomized prospective studies in patients with VT in the setting of ischemic cardiac disease. Patients are usually referred late in their clinical course for VT ablation, limiting enrollment in clinical trials and resulting in limited prospective randomized data on long-term outcomes with ablative therapy. Future research efforts should address unmet needs, including more rigorous assessment of survival benefit from VT ablation, outcomes data of VT ablation in patients with nonischemic cardiomyopathy, and assessment of strategies to improve intramural substrate ablation. Emerging technologies with disruptive potential include the use of lower ionic strength irrigants, energy delivery guided by impedance modulation, simultaneous unipolar and bipolar ablation, and novel ablation catheters, including the retractable needle-tip electrode catheter. Promising alternatives to radiofrequency ablation include alcohol ablation from the coronary arterial or venous system, direct current or pulsed field electroporation, and stereotactic body radiotherapy guided by noninvasive substrate mapping. Future studies are needed to demonstrate the safety and efficacy of these novel technologies compared with standard radiofrequency catheter ablation.
Topics: Catheter Ablation; Electrocardiography; Humans; Tachycardia, Ventricular
PubMed: 31857035
DOI: 10.1016/j.jacep.2019.09.015 -
Journal of Nippon Medical School =... 2018Idiopathic ventricular premature contractions (VPCs), defined as VPCs in the absence of obvious structural heart disease, are one of the common types of arrhythmia in... (Review)
Review
Idiopathic ventricular premature contractions (VPCs), defined as VPCs in the absence of obvious structural heart disease, are one of the common types of arrhythmia in clinical practice. They are sometimes complicated with non-sustained ventricular tachycardia (VT), and/or sustained VT with almost same QRS morphology in 12 leads ECG. Idiopathic VT (IVT) commonly occurs by focal mechanisms and the origins are distributed in a variety of sites in both ventricles. In this article, the clinical characteristics of IVT/IVPCs, the diagnostic algorithm, and how to ablate them will be reviewed.
Topics: Catheter Ablation; Electrocardiography; Humans; Tachycardia, Ventricular; Ventricular Premature Complexes
PubMed: 29731502
DOI: 10.1272/jnms.2018_85-14 -
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 -
Journal of Arrhythmia Jun 2021Coronary injury presenting as ST segment elevation (STE) during ablation procedures for different arrhythmias is a rare and most feared complication. There have been... (Review)
Review
Coronary injury presenting as ST segment elevation (STE) during ablation procedures for different arrhythmias is a rare and most feared complication. There have been multiple reports on STE during various ablation procedures in the recent past. Herein, we review various mechanisms, presentations, and management of STE observed during various ablations, including atrial fibrillation ablation cavotricuspid isthmus and ablation, supraventricular tachycardia ablations, coronary sinus ablation, and ventricular arrhythmia ablations.
PubMed: 34141005
DOI: 10.1002/joa3.12526 -
Science Translational Medicine Mar 2019Activin type II receptor (ActRII) ligands have been implicated in muscle wasting in aging and disease. However, the role of these ligands and ActRII signaling in the...
Activin type II receptor (ActRII) ligands have been implicated in muscle wasting in aging and disease. However, the role of these ligands and ActRII signaling in the heart remains unclear. Here, we investigated this catabolic pathway in human aging and heart failure (HF) using circulating follistatin-like 3 (FSTL3) as a potential indicator of systemic ActRII activity. FSTL3 is a downstream regulator of ActRII signaling, whose expression is up-regulated by the major ActRII ligands, activin A, circulating growth differentiation factor-8 (GDF8), and GDF11. In humans, we found that circulating FSTL3 increased with aging, frailty, and HF severity, correlating with an increase in circulating activins. In mice, increasing circulating activin A increased cardiac ActRII signaling and FSTL3 expression, as well as impaired cardiac function. Conversely, ActRII blockade with either clinical-stage inhibitors or genetic ablation reduced cardiac ActRII signaling while restoring or preserving cardiac function in multiple models of HF induced by aging, sarcomere mutation, or pressure overload. Using unbiased RNA sequencing, we show that activin A, GDF8, and GDF11 all induce a similar pathologic profile associated with up-regulation of the proteasome pathway in mammalian cardiomyocytes. The E3 ubiquitin ligase, Smurf1, was identified as a key downstream effector of activin-mediated ActRII signaling, which increased proteasome-dependent degradation of sarcoplasmic reticulum Ca ATPase (SERCA2a), a critical determinant of cardiomyocyte function. Together, our findings suggest that increased activin/ActRII signaling links aging and HF pathobiology and that targeted inhibition of this catabolic pathway holds promise as a therapeutic strategy for multiple forms of HF.
Topics: Activin Receptors, Type II; Activins; Adult; Aged; Aged, 80 and over; Aging; Animals; Constriction, Pathologic; Disease Models, Animal; Follistatin-Related Proteins; Frailty; Heart Failure; Heart Ventricles; Humans; Ligands; Male; Mice, Inbred C57BL; Middle Aged; Myocardium; Myocytes, Cardiac; Pressure; Proteasome Endopeptidase Complex; Proteolysis; Rats; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Severity of Illness Index; Signal Transduction; Systole
PubMed: 30842316
DOI: 10.1126/scitranslmed.aau8680 -
Europace : European Pacing,... Dec 2018
Topics: Animals; Arrhythmias, Cardiac; Atrial Remodeling; Dogs; Heart Ventricles; Myocardial Infarction; Neurons
PubMed: 29931207
DOI: 10.1093/europace/euy134 -
Reviews in Cardiovascular Medicine Mar 2022Outflow tract (OT) premature ventricular complexes (PVCs) are being recognized as a common and often troubling, clinical electrocardiographic finding. The OT areas... (Review)
Review
Outflow tract (OT) premature ventricular complexes (PVCs) are being recognized as a common and often troubling, clinical electrocardiographic finding. The OT areas consist of the Right Ventricular Outflow Tract (RVOT), the Left Ventricular Outflow Tract (LVOT), the Aortomitral Continuity (AMC), the aortic cusps and the Left Ventricular (LV) summit. By definition, all OT PVCs will exhibit an inferior QRS axis, defined as positive net forces in leads II, III and aVF. Activation mapping using the contemporary 3D mapping systems followed by pace mapping is the cornerstone strategy of every ablation procedure in these patients. In this mini review we discuss in brief all the modern mapping and ablation modalities for successful elimination of OT PVCs, along with the potential advantages and disadvantages of each ablation technique.
Topics: Catheter Ablation; Electrocardiography; Heart Ventricles; Humans; Tachycardia, Ventricular; Ventricular Premature Complexes
PubMed: 35345270
DOI: 10.31083/j.rcm2303103