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Mitral Annular Disjunction in the Context of Mitral Valve Prolapse: Identifying the At-Risk Patient.JACC. Cardiovascular Imaging Apr 2024Mitral annular disjunction (MAD), a separation between the left atrium/mitral valve annulus and the left ventricular myocardium, is frequently seen in patients with... (Review)
Review
Mitral annular disjunction (MAD), a separation between the left atrium/mitral valve annulus and the left ventricular myocardium, is frequently seen in patients with arrhythmic mitral valve prolapse. Although an association exists between MAD and ventricular arrhythmias, little is known regarding the identification of individuals at high risk. Multimodality imaging including echocardiography, computed tomography, cardiac magnetic resonance, and positron emission tomography can play an important role in both the diagnosis and risk stratification of MAD. Due to a paucity of data, clinical decision making in a patient with MAD is challenging and remains largely empirical. Although MAD itself can be corrected surgically, the prevention and treatment of associated arrhythmias may require medical therapy, catheter ablation, and an implantable cardioverter-defibrillator. Prospective data are required to define the role of implantable cardioverter-defibrillators, targeted catheter ablation, and surgical correction in selected, at-risk patients.
PubMed: 38703174
DOI: 10.1016/j.jcmg.2024.03.006 -
Europace : European Pacing,... Aug 2023This article will discuss the past, present, and future of ventricular tachycardia ablation and the continuing contribution of the Europace journal as the platform for...
This article will discuss the past, present, and future of ventricular tachycardia ablation and the continuing contribution of the Europace journal as the platform for publication of milestone research papers in this field of ventricular tachycardia ablation.
Topics: Humans; Tachycardia, Ventricular; Catheter Ablation
PubMed: 37622589
DOI: 10.1093/europace/euad225 -
JCI Insight Jul 2023Excessive activation of cardiac fibroblasts (CFs) in response to injury provokes cardiac fibrosis, stiffness, and failure. The local mediators counterregulating this...
Excessive activation of cardiac fibroblasts (CFs) in response to injury provokes cardiac fibrosis, stiffness, and failure. The local mediators counterregulating this response remain unclear. Exogenous C-type natriuretic peptide (CNP) exerts antifibrotic effects in preclinical models. To unravel the role of the endogenous hormone, we generated mice with fibroblast-restricted deletion (KO) of guanylyl cyclase-B (GC-B), the cGMP-synthesizing CNP receptor. CNP activated GC-B/cGMP signaling in human and murine CFs, preventing proliferative and promigratory effects of angiotensin II (Ang II) and TGF-β. Fibroblast-specific GC-B-KO mice showed enhanced fibrosis in response to Ang II infusions. Moreover, after 2 weeks of mild pressure overload induced by transverse aortic constriction (TAC), such KO mice had augmented cardiac fibrosis and hypertrophy, together with systolic and diastolic contractile dysfunction. This was associated with increased expression of the profibrotic genes encoding collagen I, III, and periostin. Notably, such responses to Ang II and TAC were greater in female as compared with male KO mice. Enhanced Ang II-induced CNP expression in female hearts and augmented GC-B expression and activity in female CFs may contribute to this sex disparity. The results show that paracrine CNP signaling in CFs has antifibrotic and antihypertrophic effects. The CNP/GC-B/cGMP pathway might be a target for therapies combating pathological cardiac remodeling.
Topics: Mice; Animals; Male; Female; Humans; Natriuretic Peptide, C-Type; Ventricular Remodeling; Vasodilator Agents; Fibrosis; Angiotensin II; Fibroblasts
PubMed: 37227779
DOI: 10.1172/jci.insight.160416 -
Circulation. Cardiovascular... Aug 2023Alcohol septal ablation (ASA) is a minimally invasive treatment for drug-refractory obstructive hypertrophic cardiomyopathy. Detailed assessment of pressure changes and...
BACKGROUND
Alcohol septal ablation (ASA) is a minimally invasive treatment for drug-refractory obstructive hypertrophic cardiomyopathy. Detailed assessment of pressure changes and predictors of mortality and procedure success are not well defined.
METHODS
This is a single-center study evaluating pressure changes and predictors of mortality and procedure success in transseptal ASA. Survival analysis and predictors of mortality were assessed using the Kaplan-Meier analysis and Cox regression, respectively.
RESULTS
A total of 156 patients were included (mean age, 67.3 years; 46.8% women). Left atrial (LA) pressure and left ventricular outflow tract (LVOT) gradient decreased, whereas aortic pulse pressure (PP) increased post-ASA. Patients with lower baseline mean LA pressure (
82% (gradient change median), and PP increase >19% (PP change median) had superior survival. On Cox univariable regression, baseline mean LA pressure >median (19 mm Hg; hazard ratio [HR], 2.09 [95% CI, 1.05-4.18]; =0.036), residual LVOT gradient (HR, 1.02 [95% CI, 1.01-1.03]; =0.003), and LVOT gradient percent reduction median (28 mm Hg; HR, 2.36 [95% CI, 1.17-4.76]; =0.016), baseline mean LA pressure >median (19 mm Hg; HR, 2.70 [95% CI, 1.33-5.50]; =0.006), percentage reduction in gradient CONCLUSIONS
ASA is associated with an acute decrease in the LVOT gradient and LA pressures and increase in aortic PP. Mean LA pressure, percentage decrease in LVOT gradient, and increase in PP are strong predictors of survival free of all-cause mortality following ASA and are important variables for procedural guidance.
Topics: Humans; Female; Aged; Male; Treatment Outcome; Ethanol; Cardiomyopathy, Hypertrophic; Cardiac Surgical Procedures; Hemodynamics; Ablation Techniques
PubMed: 37582173
DOI: 10.1161/CIRCINTERVENTIONS.123.013068 -
Journal of Arrhythmia Aug 2023Evidence on the impact of obesity on catheter ablation for ventricular tachycardia (VT) is scarce.
BACKGROUND
Evidence on the impact of obesity on catheter ablation for ventricular tachycardia (VT) is scarce.
METHOD AND RESULTS
We queried the Nationwide Readmissions Database to determine the hospital outcomes and procedural complications of VT ablation among the obese and nonobese populations. Obesity was associated with a more prolonged length of stay ( < .01), higher cost of hospitalization ( < .01), and higher rates of pericardial effusion or hemopericardium ( = .05) and vascular complications ( = .05). There was no significant difference in early mortality, 30-day readmissions, and other procedural complications.
CONCLUSION
VT ablation could be performed relatively safely among patients with obesity.
PubMed: 37560290
DOI: 10.1002/joa3.12892 -
Journal of the American Heart... Mar 2024Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and...
BACKGROUND
Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model.
METHODS AND RESULTS
Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], =0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; =0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve.
CONCLUSIONS
Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.
Topics: Humans; Aged; Atrial Fibrillation; Angiopoietin-2; Interleukin-6; Models, Statistical; Stroke Volume; Ventricular Remodeling; Risk Factors; Prognosis; Recurrence; Ventricular Function, Left; Biomarkers; Catheter Ablation; Treatment Outcome; Atrial Remodeling
PubMed: 38471835
DOI: 10.1161/JAHA.123.031029 -
Clinical Cardiology Jan 2024Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.
Topics: United States; Humans; Cardiomyopathy, Hypertrophic; Heart; Disease Progression; Heart Failure; Myosins
PubMed: 38269637
DOI: 10.1002/clc.24207 -
Journal of Clinical Medicine Apr 2024Ventricular fibrillation (VF) is a common cause of sudden cardiac death in patients with channelopathies, particularly in the young population. Although pharmacological... (Review)
Review
Ventricular fibrillation (VF) is a common cause of sudden cardiac death in patients with channelopathies, particularly in the young population. Although pharmacological treatment, cardiac sympathectomy, and implantable cardioverter defibrillators (ICD) have been the mainstay in the management of VF in patients with channelopathies, they are associated with significant adverse effects and complications, leading to poor quality of life. Given these drawbacks, catheter ablation has been proposed as a therapeutic option for patients with channelopathies. Advances in imaging techniques and modern mapping technologies have enabled increased precision in identifying arrhythmia triggers and substrate modification. This has aided our understanding of the underlying pathophysiology of ventricular arrhythmias in channelopathies, highlighting the roles of the Purkinje network and the epicardial right ventricular outflow tract in arrhythmogenesis. This review explores the role of catheter ablation in managing the most common channelopathies (Brugada syndrome, congenital long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). While the initial results for ablation in Brugada syndrome are promising, the long-term efficacy and durability of ablation in different channelopathies require further investigation. Given the genetic and phenotypic heterogeneity of channelopathies, future studies are needed to show whether catheter ablation in patients with channelopathies is associated with a reduction in VF, and psychological distress stemming from recurrent ICD shocks, particularly relative to other available therapeutic options (e.g., quinidine in high-risk Brugada patients).
PubMed: 38673656
DOI: 10.3390/jcm13082384 -
Journal of Cardiovascular Development... Aug 2023Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in... (Review)
Review
Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in CA, including supraventricular arrhythmias, conduction system disturbances, or ventricular arrhythmias, play a major role in CA morbidity and mortality, and thus require supplementary management. Among them, AF is the most frequent arrhythmia during CA hospitalizations and is associated with significantly higher mortality, while ventricular arrhythmias are also common and are usually associated with poor prognosis. Early diagnosis of potential arrythmias could be performed through ECG, Holter monitoring, and/or electrophysiology study. Clinical management of these patients is quite significant, and it usually includes initiation of amiodarone and/or digoxin in patients with AF, potential electrical cardioversion, or ablation in specific patients with indication, as well as initiation of anticoagulants in all patients, independent of AF and CHADS-VASc score, for potential intracardiac thrombus. Moreover, identification of patients with conduction disorders that could benefit from prophylactic pacemaker implantation and/or CRT as well as identification of patients with life-threatening ventricular arrythmias that could benefit from ICD could both increase the survival rates of these patients and improve their quality of life.
PubMed: 37623350
DOI: 10.3390/jcdd10080337 -
Journal of the American Heart... Jul 2023Background Although the critical role of pericytes in maintaining vascular integrity has been extensively demonstrated in the brain and the retina, little is known about...
Background Although the critical role of pericytes in maintaining vascular integrity has been extensively demonstrated in the brain and the retina, little is known about their role in the heart. We aim to investigate structural and functional consequences of partial pericyte depletion (≈60%) in the heart of adult mice. Methods and Results To deplete pericytes in adult mice, we used platelet-derived growth factor receptor β-Cre/ERT2; Rosa mice and compared their phenotype with that of control mice (Rosa) chosen among their littermates. Cardiac function was assessed via echocardiography and left ventricular catheterization 1 month after the first tamoxifen injection. We found mice depleted with pericytes had a reduced left ventricular ejection fraction and an increased end-diastolic pressure, demonstrating both systolic and diastolic dysfunction. Consistently, mice depleted with pericytes presented a decreased left ventricular contractility and an increased left ventricular relaxation time (dP/dt). At the tissue level, mice depleted of pericytes displayed increased coronary endothelium leakage and activation, which was associated with increased CD45 cell infiltration. Consistent with systolic dysfunction, pericyte depletion was associated with an increased expression of myosin heavy chain 7 and decreased expression of ATPase sarcoplasmic/endoplasmic reticulum Ca2 transporting 2 and connexin 43. More important, coculture assays demonstrated, for the first time, that the decreased expression of connexin 43 is likely attributable to a direct effect of pericytes on cardiomyocytes. Besides, this study reveals that cardiac pericytes may undergo strong remodeling on injury. Conclusions Cardiac pericyte depletion induces both systolic and diastolic dysfunction, suggesting that pericyte dysfunction may contribute to the occurrence of cardiac diseases.
Topics: Mice; Animals; Connexin 43; Stroke Volume; Ventricular Function, Left; Cardiomyopathies; Heart; Pericytes
PubMed: 37345826
DOI: 10.1161/JAHA.122.029279