Radiation therapy for ventricular arrhythmias.

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non-invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment.

Aggregatibacter actinomycetemcomitans pacemaker lead infection-A case report and literature review.

Aggregatibacter spp. is a rare cause for cardiac device infections. Due to limited data, the management of Aggregatibacter spp. device infections is not clearly defined but should always involve device removal and prolonged intravenous antibiotics.

Long-Term Safety and Efficacy of Transcatheter Microwave and Radiofrequency Denervation in a Chronic Ovine Model.

BACKGROUND: Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long-term safety and efficacy of transcatheter microwave RDN in vivo in normotensive sheep in comparison to conventional radiofrequency ablation. METHODS AND RESULTS: Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80-120 W for 240 s-480 s) and 12 to 16 radiofrequency ablations (180 s-240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.5 months (chronic N=15), and compared with undenervated controls (N=4). Microwave RDN produced substantial circumferential perivascular injury compared with radiofrequency at both 2 weeks [area 239.8 (interquartile range [IQR] 152.0-343.4) mm2 versus 50.1 (IQR, 32.0-74.6) mm2, P <0.001; depth 16.4 (IQR, 13.9-18.9) mm versus 7.5 (IQR, 6.0-8.9) mm P <0.001] and 5.5 months [area 20.0 (IQR, 3.4-31.8) mm2 versus 5.0 (IQR, 1.4-7.3) mm2, P=0.025; depth 5.9 (IQR, 1.9-8.8) mm versus 3.1 (IQR, 1.2-4.1) mm, P=0.005] using mixed models. Renal denervation resulted in significant long-term reductions in viability of renal sympathetic nerves [58.9% reduction with microwave (P=0.01) and 45% reduction with radiofrequency (P=0.017)] and median cortical norepinephrine levels [71% reduction with microwave (P <0.001) and 72.9% reduction with radiofrequency (P <0.001)] at 5.5 months compared with undenervated controls. CONCLUSIONS: Transcatheter microwave RDN produces deep circumferential perivascular ablations without significant arterial injury to provide effective and durable RDN at 5.5 months compared with radiofrequency RDN.

Beyond Conventional Cardiac Resynchronisation Therapy: A Review of Electrophysiological Options in the Management of Chronic Heart Failure.

The incidence of heart failure (HF) continues to grow and burden our health care system. Electrophysiological aberrations are common amongst patients with heart failure and can contribute to worsening symptoms and prognosis. Targeting these abnormalities with cardiac and extra-cardiac device therapies and catheter ablation procedures augments cardiac function. Newer technologies aimed to improvement procedural outcomes, address known procedural limitations and target newer anatomical sites have been trialled recently. We review the role and evidence base for conventional cardiac resynchronisation therapy (CRT) and its optimisation, catheter ablation therapies for atrial arrhythmias, cardiac contractility and autonomic modulation therapies.

Catheter Ablation vs Antiarrhythmic Drug Therapy for Treatment of Premature Ventricular Complexes: A Systematic Review.

There is variability in treatment modalities for premature ventricular complexes (PVCs), including use of antiarrhythmic drug (AAD) therapy or catheter ablation (CA). This study reviewed evidence comparing CA vs AADs for the treatment of PVCs. A systematic review was performed from the Medline, Embase, and Cochrane Library databases, as well as the Australian and New Zealand Clinical Trials Registry, U.S. National Library of Medicine ClinicalTrials database, and the European Union Clinical Trials Register. Five studies (1 randomized controlled trial) enrolling 1,113 patients (57.9% female) were analyzed. Four of five studies recruited mainly patients with outflow tract PVCs. There was significant heterogeneity in AAD choice. Electroanatomic mapping was used in 3 of 5 studies. No studies documented intracardiac echocardiography or contact force-sensing catheter use. Acute procedural endpoints varied (2 of 5 targeted elimination of all PVCs). All studies had significant potential for bias. CA seemed superior to AADs for PVC recurrence, frequency, and burden. One study reported long-term symptoms (CA superior). Quality of life or cost-effectiveness was not reported. Complication and adverse event rates were 0% to 5.6% for CA and 9.5% to 21% for AADs. Future randomized controlled trials will assess CA vs AADs for patients with PVCs without structural heart disease (ECTOPIA [Elimination of Ventricular Premature Beats with Catheter Ablation versus Optimal Antiarrhythmic Drug Treatment]), with impaired LVEF (PAPS [Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy] Pilot), and with structural heart disease (CAT-PVC [Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease]). In conclusion, CA seems to reduce recurrence, burden, and frequency of PVCs compared with AADs. There is a lack of data on patient- and health care-specific outcomes such as symptoms, quality of life, and cost-effectiveness. Several upcoming trials will offer important insights for management of PVCs.

Frequency Domain Analysis of Endocardial Electrograms for Detection of Nontransmural Myocardial Fibrosis in Nonischemic Cardiomyopathy.

BACKGROUND: Voltage mapping in nonischemic cardiomyopathy can fail to identify midmyocardial substrate for ventricular arrhythmias, an important cause of ablation failure. OBJECTIVES: The aim of this study was to assess whether frequency domain analysis of endocardial left ventricular electrograms (EGMs) can better predict the presence of midmyocardial fibrosis (MMF) compared with voltage amplitude. METHODS: Nonischemic cardiomyopathy patients undergoing ventricular tachycardia ablation with registered preprocedural cardiac computed tomography and late iodine enhancement were included. Presence of fibrosis at each EGM site was assessed. Bipolar and unipolar EGMs were transformed to the frequency domain using multitaper spectral analysis. Singular value decomposition of the EGM frequency spectrum was used within a supervised machine learning process to select features to predict the presence of MMF and compare against predictions using voltage amplitude. RESULTS: Thirteen patients were included (median age 57 years [IQR: 28-73 years], median ejection fraction 40% [IQR: 15%-57%]). A total of 6,015 EGM pairs were processed: 2,459 EGM pairs in MMF areas and 3,556 EGM pairs in non-MMF areas. Supervised classifiers were trained with stratified k-fold cross-validation within patients. The distribution of mean area under the curve metrics using frequency features, f, was significantly greater than voltage feature area under the curve metrics, v, (mean f = 0.841 [95% CI: 0.789-0.884] vs mean v = 0.591 [95% CI: 0.530-0.658]; P < 0.001), indicating that frequency-trained classifiers better predicted the presence of MMF. CONCLUSIONS: These data indicate the promising discriminatory value of endocardial EGM frequency content in the assessment of concealed myocardial substrate. Further studies are needed to investigate the importance of the specific frequency features identified.

A Prospective, Multicentre Randomised Controlled Trial Comparing Catheter Ablation Versus Antiarrhythmic Drugs in Patients With Structural Heart Disease Related Ventricular Tachycardia: The CAAD-VT Trial Protocol.

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.

The health digital twin to tackle cardiovascular disease-a review of an emerging interdisciplinary field.

Potential benefits of precision medicine in cardiovascular disease (CVD) include more accurate phenotyping of individual patients with the same condition or presentation, using multiple clinical, imaging, molecular and other variables to guide diagnosis and treatment. An approach to realising this potential is the digital twin concept, whereby a virtual representation of a patient is constructed and receives real-time updates of a range of data variables in order to predict disease and optimise treatment selection for the real-life patient. We explored the term digital twin, its defining concepts, the challenges as an emerging field, and potentially important applications in CVD. A mapping review was undertaken using a systematic search of peer-reviewed literature. Industry-based participants and patent applications were identified through web-based sources. Searches of Compendex, EMBASE, Medline, ProQuest and Scopus databases yielded 88 papers related to cardiovascular conditions (28%, n = 25), non-cardiovascular conditions (41%, n = 36), and general aspects of the health digital twin (31%, n = 27). Fifteen companies with a commercial interest in health digital twin or simulation modelling had products focused on CVD. The patent search identified 18 applications from 11 applicants, of which 73% were companies and 27% were universities. Three applicants had cardiac-related inventions. For CVD, digital twin research within industry and academia is recent, interdisciplinary, and established globally. Overall, the applications were numerical simulation models, although precursor models exist for the real-time cyber-physical system characteristic of a true digital twin. Implementation challenges include ethical constraints and clinical barriers to the adoption of decision tools derived from artificial intelligence systems.

Cost of cardiac stereotactic body radioablation therapy versus catheter ablation for treatment of ventricular tachycardia.

AIMS: To compare the cost of cardiac stereotactic body radioablation therapy (SBRT) versus catheter ablation for treating ventricular tachycardia (VT). BACKGROUND: Cardiac SBRT is a novel way of treating refractory VT that may be less costly than catheter ablation, owing to its noninvasive, outpatient nature. However, the true costs of either procedure are not well described, which could help inform a more appropriate reimbursement for cardiac SBRT than simply cross-indexing existing procedural rates. METHODS: Process maps were derived for the full patient care cycle of both procedures using time-driven activity-based costing. Step-by-step timestamps were collected prospectively from a 10-patient SBRT cohort and retrospectively from a 59-patient catheter ablation cohort. Individual costs were estimated by multiplying timestamps with capacity cost rates (CCRs) for personnel, space, equipment, consumable, and indirect resources. These were summed into total cost, which for cardiac SBRT was compared with current catheter ablation and single-fraction lung SBRT reimbursements, both potential reference rates for cardiac SBRT. RESULTS: The direct and total procedural costs of cardiac SBRT ($7549 and $10,621) were 49% and 54% less than those of VT ablation ($14,707 and $23,225). These costs were significantly different from current reimbursement for catheter ablation ($22,692) and lung SBRT ($6329). After including hospitalization expenses (≥$15,000), VT ablation costs at least $27,604 more to furnish than cardiac SBRT. CONCLUSIONS: Time-driven activity-based costing (TDABC) can be a helpful tool for assessing healthcare costs, including novel treatment approaches. In addition to its clinical benefits, cardiac SBRT may provide significant cost reduction opportunities for treatment of VT.

Substrate Modification Using Stereotactic Radioablation to Treat Refractory Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy.

OBJECTIVES: This study aimed to determine the feasibility of using radioablation for arrhythmogenic a substrate modification. BACKGROUND: Stereotactic body radiation therapy (SBRT) is a promising therapy for ventricular tachycardia (VT) refractory to catheter ablation. METHODS: A total of 6 male patients (median age 72 years) with ischemic cardiomyopathy (left ventricular ejection fraction 20% [interquartile range (IQR): 16%-25%]) and VT refractory to antiarrhythmic medications and catheter ablations underwent SBRT to extensive scar substrate. In addition to electroanatomical mapping, 5 of 6 patients had computed tomography segmentation using MUSIC (IHU Liryc, Univ. Bordeaux and Inria Sophia Antipolis, France). Regions of wall thinning <5 mm, calcification, and intramyocardial fat were targeted for radioablation at 25 Gy. RESULTS: The median planning target volume was 319 (IQR: 280-330) mL. Device-treated or sustained VT episodes were not significantly reduced by radioablation (median 42 [IQR: 19-269] to 29 [IQR: 0-81]; P = 0.438). However, a reduction in device shocks was observed from 12 (IQR: 3-19) to 0 (IQR: 0-1) (P = 0.046). Over a follow-up period of 231 (IQR: 212-311) days, 3 patients died of end-stage heart failure and 3 of 6 patients had possible adverse events (heart failure exacerbation, pneumonia, and an asymptomatic pericardial effusion). CONCLUSIONS: Substrate modification using SBRT assisted by computed tomography segmentation is feasible for treatment of VT in patients with ischemic cardiomyopathy. Although a significant reduction in device shocks was observed, suboptimal VT burden reduction and significant mortality rate in this cohort of patients with advanced cardiomyopathy underscore the need to improve mechanistic understanding for antiarrhythmic effects to guide dosing and targeting of scar substrates.

Remote magnetic navigation compared to contemporary manual techniques for the catheter ablation of ventricular arrhythmias in structural heart disease.

BACKGROUND: There are limited data comparing remote magnetic navigation (RMN) to contemporary techniques of manual-guided ventricular arrhythmia (VA) catheter ablation. OBJECTIVES: We compared acute and long-term outcomes of VA ablation guided by either RMN or contemporary manual techniques in patients with structural heart disease. METHODS: From 2010-2019, 192 consecutive patients, with ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM) underwent catheter ablation for sustained ventricular tachycardia (VT) or premature ventricular complexes (PVCs), using either RMN (n = 60) or manual (n = 132) guided techniques. Acute success and VA-free survival were compared. RESULTS: In ICM, acute procedural success was comparable between the 2 techniques (manual 43.5% vs. RMN 29%, P = 0.11), as was VA-free survival (manual 83% vs. RMN 74%, P = 0.88), and survival free from cardiac transplantation and all-cause mortality (manual 88% vs. RMN 87%, P = 0.47), both at 12-months after final ablation. In NICM, manual compared to RMN guided, had superior acute procedural success (manual 46% vs. RMN 19%, P = 0.003) and VA-free survival 12-months after final ablation (manual 79% vs. RMN 41%, P = 0.004), but comparable survival free from cardiac transplantation and all-cause mortality 12-months after final ablation (manual 95% vs. RMN 90%, P = 0.52). Procedural duration was shorter in both subgroups undergoing manual guided ablation, whereas fluoroscopy dose and complication rates were comparable. CONCLUSION: RMN provides similar outcomes to manual ablation in patients with ICM. In NICM however, acute success, and long-term VA-free survival was better with manual ablation. Prospective, multi-centre randomised trials comparing contemporary manual and RMN systems for VA catheter ablation are needed.

Cardiac stereotactic body radiation therapy for ventricular tachycardia: Current experience and technical gaps.

INTRODUCTION: Despite advances in drug and catheter ablation therapy, long-term recurrence rates for ventricular tachycardia remain suboptimal. Cardiac stereotactic body radiotherapy (SBRT) is a novel treatment that has demonstrated reduction of arrhythmia episodes and favorable short-term safety profile in treatment-refractory patients. Nevertheless, the current clinical experience is early and limited. Recent studies have highlighted variable duration of treatment effect and substantial recurrence rates several months postradiation. Contributing to these differential outcomes are disparate approaches groups have taken in planning and delivering radiation, owing to both technical and knowledge gaps limiting optimization and standardization of cardiac SBRT. METHODS AND FINDINGS: In this report, we review the historical basis for cardiac SBRT and existing clinical data. We then elucidate the current technical gaps in cardiac radioablation, incorporating the current clinical experience, and summarize the ongoing and needed efforts to resolve them. CONCLUSION: Cardiac SBRT is an emerging therapy that holds promise for the treatment of ventricular tachycardia. Technical gaps remain, to be addressed by ongoing research and growing clincial experience.

The Rapidly-Developing Area of Radiocardiology: Principles, Complications and Applications of Radiotherapy on the Heart.

Ventricular arrhythmias are the leading cause of sudden cardiac death. Current treatment strategies for ventricular tachycardia, including antiarrhythmic drugs and catheter ablation, have limited efficacy in patients with structural heart disease. Noninvasive ablation with the use of externally applied radiation (cardiac radioablation) has emerged as a promising and novel approach to treating recurrent ventricular tachycardias. However, the heart is generally an "organ at risk" for radiation treatments, such that very little is known on the effects of radiotherapy on cardiac ultrastructure and electrophysiologic properties. Furthermore, there has been limited interaction between the fields of cardiology and radiation oncology and physics. The advent of cardiac radioablation will undoubtedly increase interactions between cardiologists, cardiac electrophysiologists, radiation oncologists and physicists. There is an important knowledge gap separating these specialties, but scientific developments, technical optimisation, and improvements depend on intense multidisciplinary collaboration. This manuscript seeks to review the basic of radiation physics and biology for cardiovascular specialists in an effort to facilitate constructive scientific and clinical collaborations to improve patient outcomes.

Intracardiac Echocardiography to Guide Catheter Ablation of Ventricular Arrhythmias in Ischemic Cardiomyopathy.

Intracardiac echocardiography (ICE) allows intraprocedural assessment of cardiac anatomy and identification of ischemic myocardial scar and is useful for guidance of the ablation catheter and monitoring for complications. In this review, the authors discuss and provide examples of how ICE can be used to obtain additional information to understand arrhythmia mechanisms and facilitate catheter ablation therapy for ventricular arrhythmias arising from ischemic scar substrates.

Optimizing Impedance Change Measurement During Radiofrequency Ablation Enables More Accurate Characterization of Lesion Formation.

OBJECTIVES: This study sought to determine whether a novel impedance thermal imaging system (ITIS) provides an impedance measurement that is better correlated with lesion dimensions than circuit impedance during radiofrequency (RF) ablation. BACKGROUND: A 5- to 10-Ω impedance drop is clinically used to corroborate an effective RF ablation lesion. However, the contribution of local tissue heating to circuit impedance change is small and dependent on the local environment of the catheter and placement of the grounding patch. METHODS: ITIS uses ablation catheter and skin electrodes to perform 4-terminal impedance measurements with separate voltage sensing and current injection electrode pairs. Seven sheep underwent endocardial ventricular irrigated RF ablation at 40 W for 60 s. ITIS impedance and circuit impedance were both measured throughout ablation. When the sheep were sacrificed, ablation lesions were cut along their long axis; the depth, width, and surface area of the cut surface were measured. RESULTS: A total of 68 RF ablations were performed, with a median depth of 3.5 mm (interquartile range [IQR]: 2.1 to 4.9 mm), width of 8.3 mm (IQR: 5.7 to 10.8 mm), and surface area of 23.8 mm2 (IQR: 9.3 to 43.0 mm2). ITIS impedance change had good correlation with lesion depth, width, and surface area (R = 0.76, R = 0.87, and R = 0.87, respectively); and superior to circuit impedance for lesion depth, width, and surface area (p = 0.0018, p = 0.0004, and p = 0.0001, respectively). CONCLUSIONS: By optimizing the current path and using 4-terminal impedance measurement during RF ablation, the contribution of tissue temperature changes to measured impedance is better standardized to provide a more reliable measure than conventional ablation circuit impedance.

Advantages and challenges for noninvasive atrial fibrillation ablation.

PURPOSE: Although catheter ablation is an effective therapy for atrial fibrillation (AF), risks remain and improved efficacy is desired. Stereotactic radiotherapy is a well-established therapy used to noninvasively treat malignancies with precision. We sought to evaluate stereotactic arrhythmia radioablation (STAR) as a therapeutic option for treating AF. METHODS AND RESULTS: Three cancer patients with drug refractory AF were enrolled. Planning software using 3-D CT of the left atrium was used to design a desired ablation volume encompassing antral circumferential pulmonary vein isolation, roof and floor lines to create a "box" lesion set. After planning, patients were treated in the radioablation suite. STAR was able to deliver the intended radiation dose to the target in all 3 patients. No complications were observed over a follow-up period of 24 months. One patient with paroxysmal AF died from deterioration of cancer. The autopsy revealed evidence of fibroblasts and fibrogenesis in the region of atrial tissues targeted with radioablation. In one of these patients, left atrial posterior wall electrograms recorded from the esophagus before and 3 months after STAR indicated successful electrical isolation. CONCLUSIONS: This is the first report of non-invasive radioablation of the left atrium with demonstration of successful electrical isolation. Although STAR may be safe and effective in delivering ablative energy to the left atrium, further evaluation is warranted regarding effectiveness.