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.

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.

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.

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.

Frequency Content of Unipolar Electrograms May Predict Deep Intramural Excitable Substrate: Insights From Intramural Needle Catheter Ablation of Ventricular Tachycardia.

OBJECTIVES: This study sought to identify midmyocardial arrhythmogenic substrates by examining the frequency content of unipolar endocardial surface electrograms, comparing sites with transmural scar versus sites with intramural excitable substrate (IES) as identified during needle catheter ablation for ventricular tachycardia (VT). BACKGROUND: Midmyocardial arrhythmogenic substrates are a common reason catheter ablation for VT may fail. METHODS: A total of 659 intramural needle sites were studied in 26 patients (age 61 ± 9 years, 85% male, 69% nonischemic cardiomyopathy) who underwent intramural needle catheter ablation for VT. Among 136 sites where endocardial pacing did not capture (threshold >10 mA), needle pacing captured at 29 indicating IES, and did not capture at 107 indicating transmural scar. Intramural needle ablation was performed at 21 of 29 IES sites. Analysis of voltage amplitude, duration, and power spectra of endocardial and intramural needle electrograms was performed. RESULTS: IES sites compared with transmural scar had higher endocardial unipolar electrogram voltage, 0.99 (interquartile range [IQR]: 0.69 to 1.62) mV versus 0.78 (IQR: 0.61 to 1.09) mV; p = 0.038; higher unipolar intramural needle electrogram voltage, 1.16 (0.80 to 1.69) mV versus 0.76 (0.6 to 1.12) mV; p = 0.003; higher endocardial unipolar frequency power particularly in the 5- to 20-Hz band, 1.97 (IQR: 0.93 to 3.89) mV2/s versus 1.03 (IQR: 0.63 to 2.22) mV2/s; p = 0.002; and higher unipolar intramural electrogram frequency particularly in the 0 to 10 Hz range, 3.02 (IQR: 0.98 to 6.95) mV2/s versus 1.33 (IQR: 0.70 to 3.13) mV2/s; p = 0.018. Endocardial unipolar frequency in the 5- to 20-Hz band identified sites with IES, area under the curve of 0.676; p = 0.002; power frequency integral of >0.77 mV2/s provided a 90% sensitivity and 41% specificity. CONCLUSIONS: The frequency content of unipolar electrograms may complement voltage in the detection of deep intramural substrates to facilitate VT catheter ablation. (Intramural Needle Ablation for Ablation of Recurrent Ventricular Tachycardia; NCT01791543).

Irrigated Microwave Catheter Ablation Can Create Deep Ventricular Lesions Through Epicardial Fat With Relative Sparing of Adjacent Coronary Arteries.

BACKGROUND: Radiofrequency ablation depth can be inadequate to reach intramural or epicardial substrate, and energy delivery in the pericardium is limited by penetration through epicardial fat and coronary anatomy. We hypothesized that open irrigated microwave catheter ablation can create deep myocardial lesions endocardially and epicardially though fat while acutely sparing nearby the coronary arteries. METHODS: In-house designed and constructed irrigated microwave catheters were tested in in vitro phantom models and in 15 sheep. Endocardial ablations were performed at 140 to 180 W for 4 minutes; epicardial ablations via subxiphoid access were performed at 90 to 100 W for 4 minutes at sites near coronary arteries. RESULTS: Epicardial ablations at 90 to 100 W produced mean lesion depth of 10±4 mm, width 18±10 mm, and length 29±8 mm through median epicardial fat thickness of 1.2 mm. Endocardial ablations at 180 W reached depths of 10.7±3.3 mm, width of 16.6±5 mm, and length of 20±5 mm. Acute coronary occlusion or spasm was not observed at a median separation distance of 2.7 mm (IQR, 1.2-3.4 mm). Saline electrodes recorded unipolar and bipolar electrograms; microwave ablation caused reductions in voltage and changes in electrogram morphology with loss of pace-capture. In vitro models demonstrated the heat sink effect of coronary flow, as well as preferential microwave coupling to myocardium and blood as opposed to lung and epicardial fat phantoms. CONCLUSIONS: Irrigated microwave catheter ablation may be an effective ablation modality for deep ventricular lesion creation with capacity for fat penetration and sparing of nearby coronary arteries because of cooling endoluminal flow. Clinical translation could improve the treatment of ventricular tachycardia arising from mid myocardial or epicardial substrates.

Noninvasive stereotactic radioablation for the treatment of atrial fibrillation: First-in-man experience.

PURPOSE: Catheter ablation is an effective therapy for atrial fibrillation (AF). However, risks remain, and improved efficacy is desired. Stereotactic body radiotherapy (SBRT) is a well-established therapy used to noninvasively treat malignancies and functional disorders with precision. We evaluated the feasibility of stereotactic radioablation for treating paroxysmal AF. METHODS: Two patients with drug-refractory paroxysmal AF underwent pulmonary vein isolation with SBRT. After placement of a percutaneous active fixation temporary pacing lead tracking fiducial, computed tomography (CT) angiography was performed to define left atrial anatomy. A tailored planning treatment volume was created to deliver contiguous linear ablations to isolate the pulmonary veins and posterior wall. Patients were treated on an outpatient basis in the radioablation suite. Clinical follow-up was performed through at least 24 months after therapy. RESULTS: Both patients successfully underwent SBRT planning and treatment without significant early or long-term side effects up to 48 months of follow-up. One patient had AF recurrence after 6 months free of arrhythmia, while the second patient remains free of AF after 24 months with fibrosis detected on MRI scan consistent with the ablation lesion set. An incidentally noted small pericardial effusion occurred in one patient. CONCLUSION: Stereotactic radioablation may be feasible for the treatment of drug-refractory AF. Further evaluation is warranted.

Transvascular Pacing of Aorticorenal Ganglia Provides a Testable Procedural Endpoint for Renal Artery Denervation.

OBJECTIVES: This study sought to develop a method to assess renal sympathetic nerve function through localization and pacing of aorticorenal ganglia (ARG). BACKGROUND: Transcatheter renal denervation procedures often fail to produce complete renal denervation because of the lack of a physiological procedural endpoint. METHODS: High-frequency pacing was performed in the inferior vena cava and aorta in sheep (n = 19) to identify ARG pace-capture sites. Group A (n = 5) underwent injection at the ARG pace-capture site for histological verification, group B (n = 6) underwent unilateral irrigated radiofrequency ablation of ARG pace-capture sites and assessment of renal innervation at 1 week post-procedure; and group C (n = 8) underwent ARG pacing before and 2 to 3 weeks after unilateral microwave renal denervation. RESULTS: ARG pace-capture responses were observed at paired discrete sites above the ipsilateral renal artery eliciting a change in mean arterial blood pressure of 22.2 (interquartile range [IQR]: 15.5 to 34.3 mm Hg; p < 0.001) with concurrent ipsilateral renal arterial vasoconstriction, change in main renal artery diameter of -0.42 mm (IQR: -0.64 to -0.24 mm; p < 0.0001), and without consistent contralateral renal vasoconstriction. Sympathetic ganglionic tissue was observed at ARG pace-capture sites, and ganglion ablation led to significant ipsilateral renal denervation. Circumferential renal denervation resulted in immediate and sustained abolition of ARP pacing-induced renal vasoconstriction and significant ipsilateral renal denervation. CONCLUSIONS: Transvascular ARG pace-capture is feasible and recognized by concurrent hypertensive and ipsilateral renal arterial vasoconstrictive responses. Abolition of ARG pacing-induced vasoconstriction may indicate successful renal sympathetic denervation and serve as a physiological procedural endpoint to guide transcatheter renal denervation.

Transcatheter microwave ablation can deliver deep and circumferential perivascular nerve injury without significant arterial injury to provide effective renal denervation.

BACKGROUND: Clinical studies of transcatheter radiofrequency renal denervation for treating hypertension have been hampered by the lack of consistent denervation efficacy. We aimed to demonstrate the short-term efficacy and safety of transcatheter microwave renal denervation. METHODS: A novel 7F microwave system was validated in a sheep model of unilateral renal denervation. Up to two microwave ablations were delivered to each artery with maximum power at 100-110 W for 480 s. RESULTS: Catheter deployment and ablation was successful in all 19 targeted vessel segments, and ablation produced substantial circumferential perivascular injury; median ablation lesion area greater than 395 [interquartile range (IQR) 251-437] mm, depth 17.1 (IQR 15.8-18.4) mm, length 16 (IQR 12-20) mm, without collateral visceral injury. Limiting power to 100 W minimized arterial injury, while maintaining a deep circumferential perivascular ablation. Microwave denervation reduced median functional sympathetic nerve surface area at the renal hilum on antityrosine hydroxylase staining by 100% (IQR 87-100%, P = 0.0039), and median renal cortical norepinephrine content by 83% (IQR 76-92%, P = 0.0078), compared to the paired control kidney at 2-3 weeks postprocedure. CONCLUSION: Transcatheter microwave ablation can produce deep circumferential perivascular ablations over a long segment of the renal artery without significant arterial or collateral visceral injury to provide effective renal denervation.

Transcatheter non-contact microwave ablation may enable circumferential renal artery denervation while sparing the vessel intima and media.

AIMS: Trials of transcatheter renal artery denervation (RDN) have failed to show consistent antihypertensive efficacy. Procedural factors and limitations of radiofrequency ablation can lead to incomplete denervation. The aim of the study was to show that non-contact microwave catheter ablation could produce deep circumferential perivascular heating while avoiding injury to the renal artery intima and media. METHODS AND RESULTS: A novel microwave catheter was designed and tested in a renal artery model consisting of layers of phantom materials embedded with a thermochromic liquid crystal sheet, colour range 50-78°C. Ablations were performed at 140 W for 180 sec and 120 W for 210 sec, delivering 25,200 J with renal arterial flow at 0.5 L/min and 0.1 L/min. Transcatheter microwave ablations 100-160 W for 180 sec were then performed in the renal arteries of five sheep. In vitro, ablations at 140 W and 0.5 L/min flow produced circumferential lesions 5.9±0.2 mm deep and 19.2±1.5 mm long with subendothelial sparing depth of 1.0±0.1 mm. In vivo, transcatheter microwave ablation was feasible with no collateral visceral thermal injury. There was histological evidence of preferential outer media and adventitial ablation. CONCLUSIONS: Transcatheter microwave ablation for RDN appears feasible and provides a heating pattern that may enable more complete denervation while sparing the renal arterial intima and media.