Novel Epicardial Access Technique Facilitated by Carbon Dioxide Insufflation of the Pericardium for Ablation of Ventricular Arrhythmias: Lessons From the Early Experience From a Single Centre in Australia.

INTRODUCTION: Epicardial access for mapping and ablation of the epicardial substrate may be required in catheter ablation of ventricular tachycardias (VT). However, high complication rates are associated with the standard epicardial access approach. Recently, a novel method of intentional coronary vein (CV) exit with pericardial CO2 insufflation to facilitate epicardial access has been described. This study describes our initial experience with this technique. METHODS: Patients undergoing epicardial VT ablation between 1 February 2021 to 31 May 2022 at the Royal Prince Alfred Hospital, Sydney, NSW, were included in this study. Via femoral venous access, a branch of the coronary sinus was sub-selected and intentional CV exit was performed with a high tip load coronary angioplasty wire. A microcatheter was then advanced over the wire into the pericardial space, followed by pericardial CO2 insufflation, facilitating subxiphoid pericardial puncture. RESULTS: Five (5) patients underwent epicardial access for VT mapping and ablation. All patients had successful intentional CV exit and CO2 facilitated epicardial access. The mean time to successful epicardial access was 37.2±17.5 minutes. With increasing operator experience, there was improvement in epicardial access times, with the fifth case requiring only 13 minutes. There was one case of inadvertent right ventricular puncture (without haemodynamic or ventilatory compromise) due to inappropriate CO2 insufflation into the right ventricle. Epicardial access was successful on the second attempt. CONCLUSION: This is the first case series of epicardial access facilitated by CO2 insufflation in Australia. This technique enabled successful epicardial access in all patients in our early experience, with no adverse outcomes from epicardial access. With increasing operator experience, this technique may allow for more widespread adoption of up-front epicardial access for the treatment of VT.

Systematic review of electrophysiology procedures in patients with obstruction of the inferior vena cava.

AIMS: The objective of the study was to conduct a systematic review to describe and compare the different approaches for performing cardiac electrophysiology (EP) procedures in patients with interrupted inferior vena cava (IVC) or equivalent entities causing IVC obstruction. METHODS: We conducted a structured search to identify manuscripts reporting EP procedures with interrupted IVC or IVC obstruction of any aetiology published up until August 2020. No restrictions were applied in the search strategy. We also included seven local cases that met inclusion criteria. RESULTS: The analysis included 142 patients (mean age 48.9 years; 48% female) undergoing 143 procedures. Obstruction of the IVC was not known before the index procedure in 54% of patients. Congenital interruption of IVC was the most frequent cause (80%); and, associated congenital heart disease (CHD) was observed in 43% of patients in this setting. The superior approach for ablation was the most frequently used strategy (52%), followed by inferior approach via the azygos or hemiazygos vein (24%), transhepatic approach (14%), and retroaortic approach (10%). Electroanatomical mapping (58%), use of long sheaths (41%), intracardiac echocardiography (19%), transesophageal echocardiography (15%) and remote controlled magnetic navigation (13%) were used as adjuncts to aid performance. Ablation was successful in 135 of 140 procedures in which outcomes were reported. Major complications were only reported in patients undergoing AF ablation, including two patients with pericardial effusion, one of whom required surgical repair, and another patient who died after inadvertent entry into an undiagnosed atrioesophageal fistula from a previous procedure. CONCLUSION: The superior approach is most frequent approach for performing EP procedures in the setting of obstructed IVC. Transhepatic approach is a feasible alternative, and may provide a "familiar approach" for transseptal access when it is required. Adjunctive use of long sheaths, intravascular echocardiography, electro-anatomical mapping and remote magnetic navigation may be helpful, especially if there is associated complex CHD. With careful planning, EP procedures can usually be successfully performed with a low risk of complications.

Hmox1 (Heme Oxygenase-1) Protects Against Ischemia-Mediated Injury via Stabilization of HIF-1α (Hypoxia-Inducible Factor-1α).

OBJECTIVE: Hmox1 (heme oxygenase-1) is a stress-induced enzyme that catalyzes the degradation of heme to carbon monoxide, iron, and biliverdin. Induction of Hmox1 and its products protect against cardiovascular disease, including ischemic injury. Hmox1 is also a downstream target of the transcription factor HIF-1α (hypoxia-inducible factor-1α), a key regulator of the body's response to hypoxia. However, the mechanisms by which Hmox1 confers protection against ischemia-mediated injury remain to be fully understood. Approach and Results: Hmox1 deficient (Hmox1-/-) mice had impaired blood flow recovery with severe tissue necrosis and autoamputation following unilateral hindlimb ischemia. Autoamputation preceded the return of blood flow, and bone marrow transfer from littermate wild-type mice failed to prevent tissue injury and autoamputation. In wild-type mice, ischemia-induced expression of Hmox1 in skeletal muscle occurred before stabilization of HIF-1α. Moreover, HIF-1α stabilization and glucose utilization were impaired in Hmox1-/- mice compared with wild-type mice. Experiments exposing dermal fibroblasts to hypoxia (1% O2) recapitulated these key findings. Metabolomics analyses indicated a failure of Hmox1-/- mice to adapt cellular energy reprogramming in response to ischemia. Prolyl-4-hydroxylase inhibition stabilized HIF-1α in Hmox1-/- fibroblasts and ischemic skeletal muscle, decreased tissue necrosis and autoamputation, and restored cellular metabolism to that of wild-type mice. Mechanistic studies showed that carbon monoxide stabilized HIF-1α in Hmox1-/- fibroblasts in response to hypoxia. CONCLUSIONS: Our findings suggest that Hmox1 acts both downstream and upstream of HIF-1α, and that stabilization of HIF-1α contributes to Hmox1's protection against ischemic injury independent of neovascularization.

Androgens Stimulate EPC-Mediated Neovascularization and Are Associated with Increased Coronary Collateralization.

Endothelial progenitor cells (EPCs) play a key role in neovascularization and have been linked to improved cardiovascular outcomes. Although there is a well-established inverse relationship between androgen levels and cardiovascular mortality in men, the role of androgens in EPC function is not fully understood. In this study, we investigated the effects of androgens on 2 subpopulations of EPCs, early EPCs (EEPCs) and late outgrowth EPCs (OECs), and their relationships with coronary collateralization. Early EPCs and OECs were isolated from the peripheral blood of young healthy men and treated with dihydrotestosterone (DHT) with or without androgen receptor (AR) antagonist, hydroxyflutamide, in vitro. Dihydrotestosterone treatment enhanced AR-mediated proliferation, migration, and tubulogenesis of EEPCs and OECs in a dose-dependent manner. Furthermore, DHT augmented EPC sensitivity to extracellular stimulation by vascular endothelial growth factor (VEGF) via increased surface VEGF receptor expression and AKT activation. In vivo, xenotransplantation of DHT pretreated human EPCs augmented blood flow recovery and angiogenesis in BALB/c nude male mice, compared to mice receiving untreated EPCs, following hindlimb ischemia. In particular, DHT pretreated human OECs exhibited higher reparative potential than EEPCs in augmenting postischemic blood flow recovery in mice. Furthermore, whole blood was collected from the coronary sinus of men with single vessel coronary artery disease (CAD) who underwent elective percutaneous intervention (n = 23). Coronary collateralization was assessed using the collateral flow index. Serum testosterone and EPC levels were measured. In men with CAD, circulating testosterone was positively associated with the extent of coronary collateralization and the levels of OECs. In conclusion, androgens enhance EPC function and promote neovascularization after ischemia in mice and are associated with coronary collateralization in men.

Sudden Cardiac Death and Ventricular Arrhythmias in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition, with an associated increased risk of ventricular arrhythmias and sudden cardiac death. Young and asymptomatic patients, including professional athletes, are not spared this risk. Implantable cardiac defibrillators (ICDs) are highly effective in terminating malignant ventricular arrhythmias in this group, but they are associated with significant morbidity, such as inappropriate shocks and device complications. Accurate prognostication to guide ICD implantation is therefore essential. The interplay of traditional risk factors, risk modifiers and predictive models creates a complex decision-making environment for the HCM clinician. Risk stratifying tools are expanding with improved understanding of advanced imaging modalities, such as late gadolinium enhancement on cardiac magnetic resonance imaging (cMRI). Once the decision to implant a defibrillator is reached, the choice of device and programming in HCM is unique and should take into account disease substrate and younger age of patients.

Catheter Ablation of Post-Infarct VT: Mechanisms, Strategies and Outcomes.

Ventricular arrhythmias are one of the leading causes of death in patients with a prior myocardial infarction. Implantable cardioverter-defibrillators (ICDs) are very effective in the prevention of sudden cardiac death but the risk of recurrence remains an issue since defibrillation does not alter the underlying substrate. Recurrent ICD shocks are distressing and are associated with an increase in mortality. Catheter ablation is an effective treatment for recurrent ventricular tachycardia in these patients, particularly when antiarrhythmic therapy produces side effects or is ineffective. This paper reviews the underlying mechanisms of VT in patients with a prior myocardial infarction, and the indications, strategies and outcomes of catheter ablation.

National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the diagnosis and management of atrial fibrillation 2018.

INTRODUCTION: Atrial fibrillation (AF) is increasing in prevalence and is associated with significant morbidity and mortality. The optimal diagnostic and treatment strategies for AF are continually evolving and care for patients requires confidence in integrating these new developments into practice. These clinical practice guidelines will assist Australian practitioners in the diagnosis and management of adult patients with AF. Main recommendations: These guidelines provide advice on the standardised assessment and management of patients with atrial fibrillation regarding: screening, prevention and diagnostic work-up; acute and chronic arrhythmia management with antiarrhythmic therapy and percutaneous and surgical ablative therapies; stroke prevention and optimal use of anticoagulants; and integrated multidisciplinary care. Changes in management as a result of the guideline: Opportunistic screening in the clinic or community is recommended for patients over 65 years of age. The importance of deciding between a rate and rhythm control strategy at the time of diagnosis and periodically thereafter is highlighted. ß-Blockers or non-dihydropyridine calcium channel antagonists remain the first line choice for acute and chronic rate control. Cardioversion remains first line choice for acute rhythm control when clinically indicated. Flecainide is preferable to amiodarone for acute and chronic rhythm control. Failure of rate or rhythm control should prompt consideration of percutaneous or surgical ablation. The sexless CHA2DS2-VA score is recommended to assess stroke risk, which standardises thresholds across men and women; anticoagulation is not recommended for a score of 0, and is recommended for a score of ≥ 2. If anticoagulation is indicated, non-vitamin K oral anticoagulants are recommended in preference to warfarin. An integrated care approach should be adopted, delivered by multidisciplinary teams, including patient education and the use of eHealth tools and resources where available. Regular monitoring and feedback of risk factor control, treatment adherence and persistence should occur.

Atrial Fibrillation in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder with a spectrum of clinical manifestations. Patients with HCM are predisposed to developing atrial fibrillation (AF) due primarily to advanced diastolic dysfunction and left atrial (LA) dilatation and remodelling. Atrial fibrillation causes a progressive symptomatic and functional decline, as well as increased thromboembolic risk and mortality, particularly in the setting of rapid ventricular rates and left ventricular outflow tract (LVOT) obstruction. The mainstay of management of AF in HCM is a combination of non-pharmacological lifestyle and risk factor modification, long-term anticoagulation, and rhythm control with antiarrhythmic medications. There is a growing body of evidence indicating that an early and aggressive rhythm control strategy may result in more favourable outcomes.

Catheter Ablation of Recurrent Ventricular Fibrillation: A Literature Review and Case Examples.

Ventricular fibrillation (VF) electrical storm is a serious and life-threatening event, and is often triggered by premature ventricular complexes (PVCs). Catheter ablation of these PVC triggers have been described in a variety of clinical situations, including post-myocardial infarction (MI), patients with structurally normal heart, as well as in patients with Brugada Syndrome and Long QT Syndrome. We provide a literature review on this topic, using case examples for illustration.

Characterization of Endothelial Progenitor Cell Interactions with Human Tropoelastin.

The deployment of endovascular implants such as stents in the treatment of cardiovascular disease damages the vascular endothelium, increasing the risk of thrombosis and promoting neointimal hyperplasia. The rapid restoration of a functional endothelium is known to reduce these complications. Circulating endothelial progenitor cells (EPCs) are increasingly recognized as important contributors to device re-endothelialization. Extracellular matrix proteins prominent in the vessel wall may enhance EPC-directed re-endothelialization. We examined attachment, spreading and proliferation on recombinant human tropoelastin (rhTE) and investigated the mechanism and site of interaction. EPCs attached and spread on rhTE in a dose dependent manner, reaching a maximal level of 56±3% and 54±3%, respectively. EPC proliferation on rhTE was comparable to vitronectin, fibronectin and collagen. EDTA, but not heparan sulfate or lactose, reduced EPC attachment by 81±3%, while full attachment was recovered after add-back of manganese, inferring a classical integrin-mediated interaction. Integrin αVß3 blocking antibodies decreased EPC adhesion and spreading on rhTE by 39±3% and 56±10% respectively, demonstrating a large contribution from this specific integrin. Attachment of EPCs on N-terminal rhTE constructs N25 and N18 accounted for most of this interaction, accompanied by comparable spreading. In contrast, attachment and spreading on N10 was negligible. αVß3 blocking antibodies reduced EPC spreading on both N25 and N18 by 45±4% and 42±14%, respectively. In conclusion, rhTE supports EPC binding via an integrin mechanism involving αVß3. N25 and N18, but not N10 constructs of rhTE contribute to EPC binding. The regulation of EPC activity by rhTE may have implications for modulation of the vascular biocompatibility of endovascular implants.

Routine Implant of Biventricular Devices Guided by an Electroanatomic Mapping System - Ready for Prime-Time?

Biventricular devices play an important adjunctive role in the treatment of heart failure. However, biventricular device implantation is associated with significant radiation exposure and a high proportion of non-response to cardiac resynchronization therapy (CRT). The use of electroanatomic mapping (EAM) during biventricular device implantation may help overcome these issues. This article will review the literature on the role of EAM in biventricular device implantation.