Abstract Background Cardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart ...disease (SHD) and recurrent ventricular tachyarrhythmias (VT). Objectives This study assessed the value of CSD and the characteristics associated with outcomes in this population. Methods Patients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD. Results Between 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided–only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up. Conclusions CSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided–only procedure.
The recent global pandemic due to COVID-19 is caused by a type of coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite rigorous efforts worldwide to control the spread ...and human to human transmission of this virus, incidence and death due to COVID-19 continue to rise. Several drugs have been tested for treatment of COVID-19, including hydroxychloroquine. While a number of studies have shown that hydroxychloroquine can prolong QT interval, potentially increasing risk of ventricular arrhythmias and Torsade de Pointes, its effects on immune cell function have not been extensively examined. In the current review, an overview of coronaviruses, viral entry and pathogenicity, immunity upon coronavirus infection, and current therapy options for COVID-19 are briefly discussed. Further based on preclinical studies, we provide evidences that i) hydroxychloroquine impairs autophagy, which leads to accumulation of damaged/oxidized cytoplasmic constituents and interferes with cellular homeostasis, ii) this impaired autophagy in part reduces antigen processing and presentation to immune cells and iii) inhibition of endosome-lysosome system acidification by hydroxychloroquine not only impairs the phagocytosis process, but also potentially alters pulmonary surfactant in the lungs. Therefore, it is likely that hydroxychloroquine treatment may in fact impair host immunity in response to SARS-CoV-2, especially in elderly patients or those with co-morbidities. Further, this review provides a rationale for developing and selecting antiviral drugs and includes a brief review of traditional strategies combined with new drugs to combat COVID-19.
Left and bilateral cardiac sympathetic denervation (CSD) have been shown to reduce burden of ventricular arrhythmias acutely in a small number of patients with ventricular tachyarrhythmia (VT) storm. ...The effects of this procedure beyond the acute setting are unknown.
The purpose of this study was to evaluate the intermediate and long-term effects of left and bilateral CSD in patients with cardiomyopathy and refractory VT or VT storm.
Retrospective analysis of medical records for patients who underwent either left or bilateral CSD for VT storm or refractory VT between April 2009 and December 2012 was performed.
Forty-one patients underwent CSD (14 left CSD, 27 bilateral CSD). There was a significant reduction in the burden of implantable cardioverter-defibrillator (ICD) shocks during follow-up compared to the 12 months before the procedure. The number of ICD shocks was reduced from a mean of 19.6 ± 19 preprocedure to 2.3 ± 2.9 postprocedure (P < .001), with 90% of patients experiencing a reduction in ICD shocks. At mean follow-up of 367 ± 251 days postprocedure, survival free of ICD shock was 30% in the left CSD group and 48% in the bilateral CSD group. Shock-free survival was greater in the bilateral group than in the left CSD group (P = .04).
In patients with VT storm, bilateral CSD is more beneficial than left CSD. The beneficial effects of bilateral CSD extend beyond the acute postsympathectomy period, with continued freedom from ICD shocks in 48% of patients and a significant reduction in ICD shocks in 90% of patients.
The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of ...neuroscience‐based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.
Epicardial ablation has been shown to be a useful adjunct for treatment of ventricular tachycardia (VT).
To report the trends, safety, and efficacy of epicardial mapping and ablation at a single ...center over an 8-year period.
Patients referred for VT ablation (June 2004 to July 2011) were divided into 3 groups: ischemic cardiomyopathy (ICM), nonischemic cardiomyopathy (NICM), and idiopathic ventricular arrhythmias (VA). Patients with scar-mediated VT who underwent combined epicardial and endocardial (epi-endo) mapping and ablation were compared with those who underwent endocardial-only (endo-only) ablation with regard to patient characteristics, acute procedural success, 6- and 12-month clinical outcomes.
Among 144 patients referred for VT ablation, 95 patients underwent 109 epicardial procedures (94% access rate). Major complications were seen in 8 patients (8.8%) with pericardial bleeding (>80 cm(3)) in 6 cases (6.7%), although no tamponade, surgical intervention, or procedural mortality was seen. Patients with ICM who underwent a combined epi-endo ablation had improved freedom from VT compared with those who underwent endo-only ablation at 12 months (85% vs 56%; P = .03). In patients with NICM, no differences were seen between those who underwent epi-endo ablation and those who underwent endo-only ablation at 12 months (36% vs 33%; P = 1.0). In idiopathic VA, only 2 of 17 patients were successfully ablated from the epicardium.
In this large tertiary single-center experience, complication rates are acceptably low and improved clinical outcomes were associated with epi-endo ablation in patients with ICM. Patients with NICM represent a growing referred population, although clinical recurrence remains high despite epicardial ablation. Epicardial ablation has a low yield in idiopathic VA.
Abstract Background In patients referred for radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in the setting of structural heart disease, early post-procedural mortality (EM) ...has not been previously investigated. Objectives The purpose of this study was to evaluate EM after catheter ablation of scar-related VT. Methods Associations between clinical and procedural variables and EM (within 31 days of the procedure) were tested in patients with structural heart disease undergoing RFCA of VT at 12 international centers. Results Of 2,061 patients (mean age 62 ± 13 years; left ventricular ejection fraction LVEF 34 ± 13%; 53% ischemic etiology), EM occurred in 100 (5%; 95% confidence interval CI: 4% to 6%). A total of 54 (3%) patients died before hospital discharge (median 9 days after the procedure; 25% for refractory VT), including 12 (0.6%) after a major procedure-related complication. In multivariable analysis, the following factors were found to be significantly associated with EM: LVEF (odds ratio OR per percent decrease: 1.12; 95% CI: 1.05 to 1.20; p < 0.001), chronic kidney disease (OR: 2.73; 95% CI: 1.10 to 6.80; p = 0.030), presentation with VT storm (OR: 3.61; 95% CI: 1.37 to 9.48; p = 0.009), and presence of unmappable VTs (OR: 5.69; 95% CI: 1.37 to 23.69; p = 0.017). Recurrent VT was also associated with an increased risk of subsequent death (hazard ratio: 7.19; 95% CI: 5.57 to 9.28; p < 0.001) and EM (hazard ratio: 11.45; 95% CI: 7.47 to 17.59; p < 0.001). Conclusions In a contemporary cohort of patients with scar-related VT undergoing RFCA, EM occurred in 5% of cases. Clinical and procedural variables indicating poorer clinical status (low LVEF, chronic kidney disease, VT storm, and unmappable VTs) and post-procedural VT recurrence may predict EM. Identification of such features may prompt early consideration for hemodynamic support or other care to help mitigate later potential complications.
The meticulous control of cardiac sympathetic and parasympathetic tone regulates all facets of cardiac function. This precise calibration of cardiac efferent innervation is dependent on sensory ...information that is relayed from the heart to the central nervous system. The vagus nerve, which contains vagal cardiac afferent fibers, carries sensory information to the brainstem. Vagal afferent signaling has been predominantly shown to increase parasympathetic efferent response and vagal tone. However, cardiac vagal afferent signaling appears to change after cardiac injury, though much remains unknown. Even though subsequent cardiac autonomic imbalance is characterized by sympathoexcitation and parasympathetic dysfunction, it remains unclear if, and to what extent, vagal afferent dysfunction is involved in the development of vagal withdrawal. This review aims to summarize the current understanding of cardiac vagal afferent signaling under in health and in the setting of cardiovascular disease, especially after myocardial infarction, and to highlight the knowledge gaps that remain to be addressed.
Purpose
Cardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the ...pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure.
Methods
Data from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clinical practice are summarized.
Results
A harmonic interplay between the heart and the autonomic nervous system exists at multiple levels of the neuraxis. This interplay becomes disrupted in the setting of cardiovascular disease, resulting in pathological changes at multiple levels, from subcellular cardiac signaling of neurotransmitters to extra-cardiac, extra-thoracic remodeling. The subsequent detrimental cycle of sympathovagal imbalance, characterized by sympathoexcitation and parasympathetic withdrawal, predisposes to ventricular arrhythmias, progression of heart failure, and cardiac mortality. Knowledge on the etiology and pathophysiology of this condition has increased exponentially over the past few decades, resulting in a number of different neuromodulatory approaches. However, significant knowledge gaps in both sympathetic and parasympathetic interactions and causal factors that mediate progressive sympathoexcitation and parasympathetic dysfunction remain.
Conclusions
Although our understanding of autonomic imbalance in cardiovascular diseases has significantly increased, specific, pivotal mediators of this imbalance and the recognition and implementation of available autonomic parameters and neuromodulatory therapies are still lagging.
Background
Initial studies have reported excellent safety and efficacy for stereotactic body radiation therapy (SBRT) in patients with refractory ventricular tachycardia (VT).
Methods
This is a ...single-center retrospective analysis of eight consecutive patients who underwent SBRT for refractory, scar-related VT. The anatomic target for radioablation was defined based on surface 12-lead ECG VT morphology, cardiac magnetic resonance imaging, and electroanatomic mapping data when available. The target volume treated and the prescribed radiation dose (15–25 Gy) was based on the combined clinical assessment of the cardiac electrophysiologist and radiation oncologist. Ventricular arrhythmias, radiation-related outcomes, and adverse events were monitored at follow-up.
Results
Eight patients underwent nine SBRT sessions. All patients were male with an average age of 75 ± 7.3 years and mean ejection fraction of 21 ± 7%. SBRT was performed with delivery of an average of 22.2 ± 3.6 Gy in a single session with a procedure time of 18.2 ± 6.0 min. All but one session was performed on an inpatient basis. No acute complications occurred. During a median follow-up of 7.8 months (IQR 4.8, 9.9), ICD therapies decreased from median 69.5 (43.5, 115.8) pre-SBRT to 13.3 (IQR 7.7, 35.8) post-SBRT (
p
= 0.036). There were three patient deaths in the follow-up period, unrelated to SBRT. Apparent clinical benefit occurred 33% of the time after SBRT.
Conclusions
The patients experienced overall reduction in VT burden following SBRT, though not with the immediate effect seen in other patient series. Further studies (basic, translational, and clinical) are essential to determine the benefit of SBRT and if so, the optimal protocols and patient selection.
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