This document discusses a study evaluating the use of radiofrequency needle ablation for treatment of refractory ventricular arrhythmias. 31 patients with recurrent ventricular tachycardia or ventricular arrhythmia causing reduced ventricular function received needle ablation after failing standard catheter ablation and drugs. The procedure was generally safe, with 7 patients experiencing minor adverse events. At follow-up of 6-12 months, 15 patients were free of recurrent arrhythmia and 6 others had significant improvement. The study suggests radiofrequency needle ablation may be a useful option for patients with arrhythmias not adequately treated by standard approaches.

1. Infusion Needle Radiofrequency
Ablation for Treatment of
Refractory Ventricular
Arrhythmias
DOI: 10.1016/j.jacc.2018.12.070
April 2, 2019

2. BACKGROUND
• Catheter ablation is an important therapy to prevent and reduce recurrent episodes
of ventricular tachycardia (VT) in patients who have implanted defibrillators
(ICDs) and premature ventricular beats and nonsustained VT causing significant
symptoms or contributing to depressed ventricular function.
• In multicenter trials, however, approximately one-half of the patients have at least
one recurrence of VT.
• When ablation and antiarrhythmic drugs fail, therapeutic options are often limited
and outcomes are poor.
• In one series, patients undergoing additional surgical and/or transcoronary alcohol
ablation after catheter ablation failed had a 6-month mortality rate of 17% and a
55% rate of recurrent VT.

3. • Effective ablation requires identification and damage of the tissue causing
the arrhythmia. Endovascular catheters are limited to ablation of tissue
within about 7 mm of the endocardial surface.
• Percutaneous access to the pericardial space allows ablation of tissue in the
subepicardium, but is often limited by epicardial fat, inaccessibility due to
pericardial adhesions in patients who have had prior cardiac surgery, and
risk of collateral injury to adjacent coronary arteries.
• Inaccessibility of arrhythmogenic areas is an important cause of ablation
failure and likely explains the worse outcome of ablation in nonischemic
heart disease, as compared with coronary artery disease.
• To identify and ablate arrhythmia substrate that is deep to the endocardium,
we developed a technique of radiofrequency (RF) needle infusion ablation
for myocardial use.

4. • Following enhancements to the catheter design, this U.S. Food and
Drug Administration investigational device exemption trial was
initiated to assess the safety and outcome of RF needle infusion
ablation in patients with recurrent ventricular arrhythmias that had
failed control with conventional irrigated RF ablation and
antiarrhythmic drug therapy.

5. METHODS
• Patients with episodes of sustained monomorphic VT or incessant
ventricular arrhythmia for >20% of beats in a 24-h period associated with
reduced ventricular function (ejection fraction <40%) that had failed to
respond to antiarrhythmic drug therapy due to inefficacy or intolerance and
failed catheter ablation due to spontaneous recurrence of the arrhythmia
were offered participation in the study.
• Exclusion criteria included: idiopathic VT not causing depressed ventricular
dysfunction, protruding left ventricle (LV) thrombus, myocardial infarction
within 2 months, Class IV heart failure or cardiogenic shock unless due to
VT, contraindication to heparin, allergy to radiographic contrast dye, severe
aortic stenosis or mitral regurgitation with a flail mitral leaflet, unstable
angina, thrombocytopenia <50,000, and other disease processes likely to
limit survival to <12 months.

6. • Mapping and ablation were performed with patients under conscious
sedation or general anesthesia.
• Electrophysiological catheters and an intracardiac echocardiography
(ICE) catheter were placed from femoral arteries or veins.
• LV access was achieved by a retrograde aortic or transseptal atrial
approach.
• Systemic anticoagulation was achieved with heparin.
• Electroanatomical maps were created using a 3-D mapping system
(CARTO 3; Biosense Webster, Irvine, California).
• Ventricular anatomy and catheter position were observed with ICE
(SoundStar; Biosense Webster or Viewflex; Abbott Medical).

7. • Endocardial voltage maps of the chamber of interest were generated in
sinus or paced rhythm with a 3.5-mm tip standard ablation catheter
(ThermoCool SmartTouch, CF-sensing catheter; Biosense Webster) or
a multi-electrode catheter (PentaRay NAV Catheter; Biosense
Webster).
• Low-voltage scar was defined as an area having a bipolar electrogram
amplitude <1.5 mV; low unipolar LV voltage was defined as <8.3 mV
for septum and LV and <5.5 Mv for right ventricle (RV) free wall.

8. NEEDLE ABLATION CATHETER
• The needle ablation catheter is an 8-French catheter
with a dome (tip) electrode and single ring
electrode. The dome electrode has a single hole
through which the 27-g needle electrode can be
extended for up to 10 mm. The needle is electrically
isolated from the dome electrode and contains a
thermocouple within its lumen near the tip. A
position sensor allows display of the dome
electrode and distal catheter shaft position on the
electroanatomic mapping system.
• The length of the needle was adjusted to be less
than myocardial thickness in the targeted region,
and was initially set to 6 to 9 mm (median, 7 mm).
The dome electrode port and needle are each
independently irrigated with heparinized saline at 1
ml/min during mapping. The needle is used as an
electrode for recording unipolar electrograms and
bipolar electrograms (between the needle and the
dome or ring electrodes).

9. • Unipolar needle and dome electrograms are recorded on multiple
channels to allow high-pass filtering at different settings of 0.5, 30, or
40 Hz. Bipolar recordings were high-pass filtered at 30 or 40 Hz.
Pacing can be performed from the needle or dome electrode. Failure to
capture with unipolar pacing at 10 mA and ≥2 ms pulse width was
considered an indication of electrically unexcitable tissue due either to
scar or acute RF lesion creation.

10. ABLATION PROCEDURE
• Initial mapping to identify ablation targets was performed as previously
described with a standard irrigated ablation or multispline mapping catheter.
Ventricular geometry was defined with ultrasound and voltage mapping. If
the arrhythmia was not present at baseline it was induced with programmed
stimulation with up to 4 extra stimuli and burst pacing and with epinephrine
or isoproterenol infusion if required. Hemodynamically unstable
arrhythmias were terminated by pacing or cardioversion. The initial
mapping catheter was then exchanged for the needle ablation catheter. If VT
produced hemodynamic instability, activation and entrainment were
assessed at only selected sites during brief episodes. Because needle
ablation can spare the endocardium, conventional endocardial irrigated RF
ablation was allowed at the discretion of the investigator (Biosense Webster,
ThermoCool, or Surround Flow with maximum power of 50 W).

11. • Endocardial sites thought to be closest to the arrhythmia origin were
selected for needle deployment. For scar-related arrhythmias, areas of
low bipolar or unipolar voltage thought to be closest to the VT circuit
based on activation and entrainment mapping, or for unstable VTs,
pace-mapping, were initially evaluated. For premature ventricular
complexes (PVCs), the area of earliest endocardial activation was
initially evaluated. Using ICE and fluoroscopic guidance to attempt to
achieve a perpendicular position of the catheter tip to the
endocardium, the needle was extended into the myocardium and the
needle irrigation was paused.

12. • Unipolar pacing from the needle electrode was performed to assess tissue
excitability at 10 mA, 2 ms pulse width stimulus strength. If there was no
capture pacing at 10 mA, 9 ms pulse width could be assessed. If no capture
was detected, the needle was retracted and mapping continued. At sites
selected for ablation 1 ml of 50:50 saline and radiographic contrast
(iopamidol [76%]) solution was injected manually and tissue staining was
assessed with fluoroscopy. If the site was still selected for ablation, normal
saline was infused through the needle at 2 ml/min for 60 s (CoolFlow pump;
Biosense Webster) followed by initiation of RF energy during continued
saline irrigation at 2 ml/min. Dome irrigation was 1 ml/min for mapping
and ablation. RF was applied in a temperature-controlled mode set to 60ºC
and with power initially limited to 15 to 35 W and manually increased to
achieve a temperature of 60ºC.

13. • Maximum power and lesion duration were 50 W and 120 s, respectively. Needle
infusion was then paused and unipolar needle pacing was performed to assess
post-ablation capture. Absence of capture at the stimulus output that had
previously captured was taken as evidence of lesion creation. RF was terminated
for an increase in impedance of >2 to 3 ohms after the initial fall.
• The procedure goal was abolition of all inducible sustained monomorphic VTs, or
abolition of the ambient or provokable nonsustained arrhythmia that was the
ablation target, or absence of further identifiable target sites. For scar-related VTs
we sought to render the target region unexcitable to needle pacing that captured
prior to ablation. In patients with low-voltage scar, ablation was performed at
multiple sites that captured surrounding the initially identified site. Programmed
stimulation was then typically repeated and other induced VTs were targeted.
• For septal arrhythmias, needle insertion could start from either the right or left side
of the septum, followed by the opposite side if ablation at the initial sites was
ineffective or good target sites were not identified.

14. POST PROCEDURE
• Anticoagulation and arrhythmia drug management were left to the
discretion of the treating physicians as per usual laboratory protocols.
• Patients underwent anticoagulation treatment with heparin overnight
and then either aspirin, warfarin, or a direct-acting anticoagulant for at
least 3 months.
• Follow-up visits occurred 3 to 6 weeks and 5 to 7 months after
ablation.
• An echocardiogram was obtained prior to hospital discharge and 5 to 7
months after ablation.

15. PRIMARY ENDPOINTS
• The prespecified efficacy endpoint for sustained VT was control of VT defined by
freedom from hospitalization for recurrent VT during the 6 months following ablation.
• Efficacy endpoint for ventricular arrhythmia causing significant ventricular dysfunction
was a decrease in ambient ventricular arrhythmia to <5,000 ventricular beats daily.
• Safety endpoint was absence of all serious adverse events that are potentially device
related and occur within 30 days of the ablation procedure.
• A clinical or presumptive clinical VT is one that has been documented to occur
spontaneously or is within 20 ms in cycle length of a VT that has been documented to
occur spontaneously.
• Modification of the VT substrate was defined as abolition of at least one inducible
sustained VT but continued presence of another inducible sustained VT.

16. RESULTS
STUDY POPULATION
• A total of 42 patients met the entry criteria
and were consented for the procedure.
• Ablation with the needle catheter was not
performed in 11 patients: because in 10
patients the arrhythmia origin was identified
on the endocardium and conventional
irrigated ablation was successful and in 1
patient the procedure was aborted when
intracardiac ultrasound identified a large
mobile thrombus in the right ventricle prior to
placement of electrophysiological catheters.
• A total of 31 patients had ablation with the
needle catheter.

20. SAFETY
• Any adverse event requiring therapy within 30 days
occurred in 7 patients (23%)
• One patient developed a pericardial effusion that was
drained percutaneously without sequelae . One patient
experienced LV lead dislodgement. One patient developed
heart block from septal ablation, which was expected. One
patient with a left ventricular ejection fraction of 39%, but
heart failure related to catecholamine cardiomyopathy from
a recently resected pheochromocytoma and VT storm
experienced heart failure exacerbation requiring diuresis
after the procedure. One patient experienced a pulmonary
embolism 4 days after the procedure following a long
airplane flight and recovered after thrombolytic therapy.

21. • A very small amount of coagulum on the dome electrode of the needle
catheter was observed during the procedure in 12 patients. This occurred
following an impedance rise. No clinically evident embolic events occurred.
• Echocardiograms were obtained prior to hospital discharge in 28 patients,
and were interpreted by the respective institution’s imaging specialists
independent of the study. Left ventricular ejection fraction decreased by
>5% in 2 patients, increased by >5% in 4 patients, and changed <5% in the
remainder. A new small pericardial effusion was noted in the patient who
had pericardiocentesis at the time of the procedure. In 2 patients, mitral
regurgitation that was mild pre-procedure was mild to moderate after the
procedure with no new structural abnormalities of the valve identified.

22. FOLLOW-UP
• At discharge, antiarrhythmic drugs were unchanged in 10
patients and decreased in 21 patients.
• During a median follow-up of 259 (range, 204 to 339) days from
the initial procedure, 15 patients were free from recurrent
arrhythmia: 4 for whom PVCs were the predominant target and
11 with sustained VT.
• In addition, 6 patients, who had frequent or incessant VT
episodes prior to ablation, had marked improvement with 1 to 6
episodes in the 6 months after ablation.
• There was 1 death from pneumonia 6 months after ablation in a
patient who suffered recurrent VT that was not related to the
death.
• Repeat catheter ablation was performed in 5 patients in the
failed group.

23. • Repeat needle ablation was performed in 2 patients. One patient with non-
ischemic cardiomyopathy who required intravenous lidocaine for VT suppression
prior to his initial procedure had 2 VT episodes terminated by his ICD after
ablation. After a second needle ablation 9 weeks after initial ablation, he remained
free of further VT (last follow-up at 201 days after the second procedure). A
patient with hypertrophic cardiomyopathy who continued to have inducible and
spontaneous VT from the basal LV after 2 needle ablation procedures had surgical
septal myectomy, but continued to have occasional VT. Three patients had
subsequent endocardial ablation procedures with conventional irrigated catheters.
Two had endocardial ablation that acutely modified inducible VT in 1 patient and
abolished inducible VT in the other. The fifth patient had multiple morphologies of
PVCs that were abolished acutely with ablation, but had recurrent PVCs with
different morphologies during follow-up.

24. ILLUSTRATIVE CASE OF SEPTAL VTs DUE TO LAMIN
CARDIOMYOPATHY
• A patient with lamin cardiomyopathy, atrioventricular block, and LV
ejection fraction 28% had recurrent VTs originating from the basal
septum and periaortic area.
• Prior ablation included endocardial RF ablation, transcoronary ethanol
ablation of proximal septal arteries, and simultaneous unipolar
ablation from both sides of the septum.
• At electrophysiology study, 5 different morphologies of VT were
induced by catheter manipulation and pacing but mapping was limited
by spontaneous changes in QRS morphology and hemodynamic
intolerance.

25. • Needle ablation targeted the low-voltage region of the basal to mid
septum from the right ventricle and LV. Evidence of intramural
substrate included septal areas of pre-systolic potentials on the needle
that were not seen from the overlying dome electrode and areas where
pacing stimuli delivered from the needle, but not the dome electrode
on the overlying endocardium captured.
• Needle RF lesions were delivered extending from the septum into the
periaortic region. Following ablation, burst pacing no longer provoked
VT. Amiodarone was reduced to 200 mg daily.
• He remained free of VT for 21 months when he had a single episode
of VT during a heart failure exacerbation.

26. A=An RAO view shows the needle catheter traversing the tricuspid valve and
curved toward the septum. The needle is deployed in the septum and a small
area of injected contrast staining (arrow) is evident.
B=The approach to the inferior septum from a transseptal approach.
C=The electroanaomic maps of the LV and RV, viewed from the inferior
aspect of the heart, with the apex at the top. Black tags indicate sites where
the needle was inserted, but no ablation performed, often because needle
pacing failed to capture. Maroon tags are needle ablation sites.

27. DISCUSSION
• Ventricular arrhythmia substrate deep to the endocardium is an important
cause of failure of VT ablation. An infusion needle ablation catheter was
developed to attempt to address this problem.
• We previously demonstrated feasibility of this approach in 8 patients using
a prototype catheter. The catheter was then redesigned to irrigate the lumen
through which the needle extends, and to reinforce the handle.
• The present multicenter series with this catheter is the largest experience
with intramural needle ablation in humans. In a population of patients with
difficult to control arrhythmias who had failed antiarrhythmic drug therapy
and a median of 2 prior catheter ablation procedures, abolition of the
arrhythmia was achieved in 48% and substantial improvement was achieved
in an additional 19% with acceptable safety.

28. • In a series of 67 patients who had the alternatives of surgery and/or
transcoronary ethanol ablation the 30-day and 6-month mortality rates
were 10% and 17%, respectively, and more than one-half had
arrhythmia recurrences. Several interesting observations help improve
our understanding of intramural ablation and its potential.
• Identification of intramural ablation targets is a major challenge. Initial
target sites were selected based on anatomic information from voltage
mapping and intracardiac ultrasound imaging along with endocardial
mapping. This approach produced reasonable outcomes. Repeated
insertion of the 27-gauge needle into the myocardium for mapping was
well tolerated. Pre-procedural imaging of scar, which was not
routinely done, would be of great interest to potentially improve
mapping guidance.

29. • As expected, many patients had unmappable VTs, leading to a substrate
ablation type of approach, with needle insertion into the region below the
best endocardial sites and ablation if pacing on the needle captured at these
regions. Prior experimental work has shown that creation of large RF
ablation lesions with the needle requires infusion of saline into the
myocardium. This likely creates a “virtual electrode” in the tissue that
distributes the RF current; however, continued irrigation during RF also
cools the electrode, which also may permit increased current delivery at the
target temperature. The injection of saline into the tissue likely has
electrophysiological consequences, and we observed arrhythmia
suppression by injection of saline into the tissue. Hence, confirmation of the
location of the needle in a potential VT circuit by recording or pacing from
the needle during VT was more limited than we anticipated.

30. • Infusion needle ablation can spare the endocardium, and, hence,
additional endocardial ablation will be warranted in some patients.
Although all of our patients had failed prior endocardial ablation, we
did identify endocardial sites that captured with pacing and we elected
to apply additional endocardial RF ablation at these sites in 6 patients
after needle ablation was judged acutely effective. The role of this
approach remains to be defined, but a favorable effect of endocardial
ablation in 2 patients with recurrent VT during follow-up suggests that
additional endocardial ablation will be important for some patients.

31. • This study provides important insights into the safety of intramural saline injection into
the ventricular myocardium. With each needle ablation we injected 3 ml of saline/contrast
prior to RF application and continued infusing at 2 ml/min for the duration of the RF
application, hence, another 3 ml of saline for a 90-second RF application. The
myocardium is organized in layers and appears to easily accommodate this volume of
fluid, which likely drains through lymphatics, and Thebesian vessels. In 1 case, however,
we did raise an epicardial bleb likely due to dissection of fluid through the tissue. This
occurrence raises an important safety concern, exposing a potential mechanism of
tamponade. Indeed, this occurred in 1 patient with a focal LV outflow tract arrhythmia, in
whom scar may have been absent. On the other hand, despite multiple RF applications, up
to 66 applications in a patient with scar-related VT, intramural fluid collections and
significant pericardial effusion were not observed in other patients. All procedures used
intracardiac ultrasound that is very sensitive to detection of pericardial effusions.
Dissecting intramural hematomas have been reported with endocardial RF ablation,
possibly related to intramural hemorrhage. We believe it is prudent to limit saline
injection to sites where ablation is being performed and otherwise avoid myocardial fluid
injection, particularly when there is no evidence of scar.

32. • We occasionally observed small impedance rises and a very small amount of coagulum at
the dome electrode port for the needle, similar, but smaller, than that which we have seen
with currently approved irrigated and nonirrigated RF ablation catheters. We speculate
that this may occur when the needle is not completely inserted into the myocardium. With
a gap between the dome electrode and the tissue, the portion of the needle in the blood
pool may reach temperatures sufficient for coagulum formation despite irrigation of the
lumen in the dome. Whether increasing this irrigation rate would be beneficial is not
known. In all cases, the coagulum was small and adherent to the dome electrode. The
catheter was always inspected for coagulum when removed. No coagulum was observed
without a prior impedance increase during RF. We did not observe coagulum when RF
delivery was promptly terminated for any impedance increase. This precaution may be
important for preventing coagulum formation. No clinically evident embolic events
occurred, but we did not obtain pre-procedure and post-procedure magnetic resonance
imaging.

33. STUDY LIMITATIONS
• This is an observational series of patients who had failed available ablation
and antiarrhythmic drug therapies.
• There is no control group.
• We did not mandate another endocardial or epicardial ablation be performed
at the same procedure prior to using the needle, but as noted did withdraw
10 patients after endocardial mapping suggested, and ablation confirmed,
that the VT could be interrupted without needle ablation.
• The prespecified follow-up period of a minimum of 6 months is relatively
short, but was thought to be sufficient in view of the severity of the
arrhythmias.
• Procedures were performed at a small number of experienced centers.

34. • Ablation technologies are evolving and we do not have direct
comparison data for needle ablation versus bipolar ablation, which was
investigational during this study, although bipolar ablation and
simultaneous 2-site unipolar ablation had failed in 2 patients who had
successful needle ablation.
• Our prior work supported the safety of the saline infusion and energy
parameters used; it is possible that lesion size could be further
increased by altering injectate conductivity or other parameters.

35. CONCLUSIONS
• Infusion needle RF ablation offers a new ablation therapy for patients
with recurrent VT that, in this multicenter series, provided significant
potential benefit and acceptable safety.
• A strategy of targeting VT based on endocardial mapping data appears
reasonable.
• Further studies to refine methods for targeting intramural substrate and
confirm efficacy and safety are warranted.

36. THANK YOU