Cryoballoon ablation for atrial

fibrillationThe Newcastle experience

By Nick Jackson

CryoenergyThe first animal based studies on cryoenergy ablation were performed in ’91.

Freezing causes immediate freeze rupture of cells and delayed necrosis and apoptosis. Freezing also causes vascular stasis and leading to ischaemia.

Cell death occurs instantly when temperature falls below -40º

◦Slow thawing increases damage through recrystallization, and prolonged hyperosmolarity/cell stress

◦Repeat freezing: Tissue cooling is faster, ice crystals grow larger, and greater depth of freezing is achieved.

Wound HealingCryogenic lesions in muscle heal by fibrosis like an ischaemic infarct

Fibrotic area is sharply demarcated and homogenous

Collagen fibres, elastin and fibroblasts resist damage to freezing◦They preserve the tissue architecture and serve as scaffold for repair

◦Damaged collagen is slowly absorbed and replaced

Cryo Lesion

Advantages of CryoPreservation of extracellular matrix

Less/no risk of atrio-oesopageal fistula

Less/no risk of PV stenosis

Preservation of endothelium

Minimal thrombus formation and less stroke risk.

Painless

No need for general anaesthesia but pts do get an ‘ice-cream’ headache.

Cryoadhesion

Less difficulty for the operator

6

The Arctic Front Balloon The Arctic Front Balloon CatheterCatheter

7

Method

200 consecutive pts who had CBA for symptomatic af between march 2008 and feb 2011.

Documented af of ecg.

Exclusion criteria: Severe valvular pathology or echo abnormality, decompensated heart failure, recent AMI or CABG surgery or severe comorbidity.

MethodLocal anaesthesia and sedation.

EP catheters placed in the CS and SVC via the femoral vein and a trans-septal puncture was performed.

Pts were anticoagulated with either warfarin prior, IV heparin to achieve an ACT >250 or a combination.

Venograms of all PVs were then obtained with a multipurpose catheter and PV diameters were recorded.

FlexCath sheath in RLPV

MethodA Lasso catheter was then advanced to the LA to measure electrical activity in all PVs.

For ablation the lasso catheter was removed and a Cryocath arctic front balloon was advanced to the LA.

23mm or 28mm balloon was used.

LUPV was wired with the balloon inflated at the vein os, contrast is injected to check vein occlusion/contact.

A 5 min freeze is applied and then repeated and so on for all four PVs.

Excellent Occlusion

LUPV good occlusion

RUPV good occlusion

MethodPhrenic nerve stimulation was performed during right sided PVI.

The Lasso catheter was then replaced into the LA to check for complete PVI.

If ongoing potentials were recorded then further CBA were performed and if these were unsuccessful a RFA catheter was used.

Pts who had successful procedures tended to have their AADs and or warfarin ceased 1 -3 months following at the cardiologists discretion.

Poor Occlusion

LUPV occlusion with poor balloon position (28mm).

RLPV typical leak

RLPV good occlusion

Freeze

MethodPts were followed up with ecgs and clinic visits at 0, 3, 6 and 12 months and then at cardiologist discretion.

routine holter at 3/12 and then further telemetry generally to inv symptoms.

Correspondence from GPs and other specialists was reviewed and all pts were contacted by phone at the end of their f/u.

Pt demographicParoxysmal Persistent P valve

Patients 139 61

Age 62.3 (SD 6.6 years) 59.3 (SD 9.5 years) 0.044

Sex 46 (33%) Female, 93 (66%) Male 13 (21.3%) Female, 48 (78.7%) Male 0.09

Average time to CBA, years

5 (2.63 - 9) 4 (1 - 9)

Parox fqncy weekly

1.5 (0.4 - 3.5) N/A

Thyroid Function 5 (3.6%) Hypothyroid, 10 (7.2%) Hyperthyroid, 124 (89.2%) Euthyroid

3 (4.9%) Hypothyroid, 5 (8.2%) Hyperthyroid, 53 (86.9%) Euthyroid 0.87

LVEF 61.8% (SD 8.7%) 57.4% (SD 13%) 0.0058

By grouping LVEF ≤30% (1), 31-49% (5), ≥50% (133) LVEF ≤30% (5), 31-49% (6), ≥50% (49)

LA diameter 41.0mm (SD 6.6mm) 45.8mm (SD 7.6mm) 0.0005

By grouping 68 (48.9%) normal, 55 (39.6%) mild, 3 (2.2%) mild-mod, 11 (7.9%) moderate, 2 (1.4%) severe

16 normal, 22 mild, 1 mild-mod, 12 moderate, 2 mod-severe, 6 severe 0.0004

Echo abnormality 6/139 (4.3%), (Moderate valvular disease, pulm htn or LV dilatation) 2/61 (3.3%) 0.73

LVH Mild 9/139 (6.5%) 2/61 (3.3%) 0.36

Hypertension 73/139 (52.5%) 27/61 (45.9%) 0.28

Diabetes Mellitus DM 10/139 (7.2%), IGT 3/139 (2.2%) 5/61 (8.2%) 0.79

Stroke/TIA 11 Pre-procedure, 2 post, 1 TIA pre, 1 TIA post 3 Prior 0.18

CCF/ EF ≤30% 15/139 (10.8%) 17/61 (27.9%) 0.002

Alcohol (>2 SD dly)

43/100 (43%) 13/43 (30.2%) 0.15

Smoking status Current 4%, Prior 24% Current 8.7%, Prior 8.7% 0.71

Procedure ResultsParoxysmal Persistent P value

Prior Procedures 12 Prior AF and 5 Prior flutter ablations (17) 1 Prior AF and 5 prior flutter ablations (6) 0.07

Repeat Procedures 11 RF, 6 Cryo, 4 Combined, 1 had 2 RF repeats (23) 7 RF, 2 Cryo, 2 Combined, 1 had 2 RF repeats (13) 0.96

Procedural anticoagulation 69 Heparin (49.6%), 44 Warfarin (31.7%), 26 Combined (18.7%)

27 Heparin (44.3%), 28 Warfarin (45.9%), 6 Combined (9.8%)

0.09

Anti-arhythmic at 3 months 43 Nil, 6 Amiodarone, 30 Flecainide, 57 Sotalol 10 Nil, 10 Amiodarone, 5 Flecainide, 33 Sotalol, 1 Flec/Sotalol

0.0006

Cryoballoons Used 28mm: 99, 23mm: 37, Both: 3 28mm: 47, 23mm: 13, Both: 1 0.69

Procedure duration (min) 140 (120 - 170) Min 85, Max 289

Fluroscopy duration (min) 31 (23 - 39) Min 11, Max 97

Number of freezes per vein LSPV 2.6 +/- 1, LIPV 2.5 +/- 0.9, RSPV 2.1 +/- 0.7, RIPV 2.4 +/- 0.9, L com 4.6 +/- 2.2, RMPV 1.2 +/- 0.4 <0.0001

Isolation rate per vein (balloon only) LSPV 96.7%, LIPV 98.3%, RSPV 95.3%, RIPV 90.2%, L com 83.3%, RMPV 100% 0.00013

Isolation rate per vein (balloon and RF, 20/200 used RF)

LSPV 98.3%, LIPV 98.9%, RSPV 96.4%, RIPV 97.4%, L com 94.4% 0.533

Total Isolation rates 93.6% (balloon only), 97.7% (Balloon and RF) 0.0032

Isolation rates per balloon 23mm: 96.5%, 28mm: 92.6%, Both: 100% 0.058

Phrenic nerve palsy rates per balloon 23mm: 4 transient, 2 persistent (12%), 28mm: 5 transient, 4 persistent (6.3%) 0.19

Procedure Duration

Freedom from AF

Freedom by Early Recurrence

Redo Procedures200 Pts were followed for up to 3 years with a mean of 18 months and 8 days.

4 were lost to f/u. 7 did not reach the end of the blanking period

35 repeat procedures. (22 RF, 6 Both, 8 CBA). Median time to rpt was 199 (113-337) days and median f/u was 389 (250-566) days.

Paroxysmal Pts: 35% had no further recurrence and 50% had ≤1 recurrence after rpt.

Persistent: 33.3% had no further recurrence following rpt.

ComplicationsMinor (33) Major (2)

9 Transient PNP, 6 PNPs

Right upper lobectomy for Pulm infarction

6 Minor haemoptysis Gastroparesis present > 1 year

3 Fluid overloads/ APOs

1 Pneumonia3 Pleuritic CP persisting

beyond procedure

1 Oesophageal ulceration

1 Transient visual field defect (TIA)

2 Vasovagals requiring medical Tx

<2% uncomplicated haematomas

1 Right Iliac vein perforation <2% Headaches requiring more than simple analgesia

Discussion

In this study 56.5% and 36.5% of patients were free from symptomatic AF at two years in the paroxysmal and persistent groups respectively.

This compares with the previously quoted rates of 47-78% at three years for freedom from AF with RFA (1-4).

Recent studies also using CBA have shown rates of freedom from paroxysmal AF of 74% at eighteen months (10), 69.9% at twelve months (14), 52.5% at a mean of nine months (13) and 70% at a mean of nine months (12).

The recurrence rates for persistent AF patients range from 42% at eighteen months (10) to 50% at a mean of nine months (13).

DiscussionPatients with persistent AF were younger but had significantly larger LA diameters (41 versus 45.8mm, p 0.0005) and lower LVEFs (61.8% versus 57.4%, p 0.0058).

Persistent AF pts had less freedom from recurrent episodes in this trial and in the largest CBA trial by Neumann et al. and these tended to be of greater duration and often still required AADs or CV for termination.

Recurrences were 72.6% and 51.5% for patients who had had ≤2 recurrences (self limiting recurrences for <24 hours only in the paroxysmal group).

Malmborg et al. (13) reported 17.5% of patients treated with CBA for symptomatic AF had a reduction in symptom frequency as assessed at clinic visits.

Infrequent recurrent episodes of AF may be initiated by atrial ectopy outside of the pulmonary veins and pulmonary vein isolation may limit the maintenance of AF or convert persistent AF to paroxysmal AF in this situation (15, 9).

Procedure Duration

Over 200 CBA procedures the median procedure duration of 140 minutes and fluoroscopy time of 31 minutes compares favourably to >200 minutes on average for RFA (1,3).

Prior CBA studies have shown median procedural times of 155-232 minutes and fluoroscopy times of 35-58 minutes (10-13, 21, 25).

As with the study by Van Belle et al. procedure and fluroscopy times plateau after around 30 procedures (11).

STOP AF trial reported procedural durations as high as 371 minutes (200-650) and may reflect a lack of procedural experience by a number of operators in this trial (14).

Isolation Rates93.6% of pulmonary veins isolated with CBA alone. In a further 10% of patients a conventional RF catheter was used to achieve 97.7% isolation.

A conventional catheter allows small breaks in circumferential isolation to be joined. Limited application reduces the risk of serious RFA complications caused by excessive heating and structural changes in the pulmonary veins such as PVS, AOF and possibly stroke (21).

RSPV received significantly fewer CBAs possibly due to concern over phrenic nerve palsy and the RIPV and LCPVs were significantly more difficult to isolate with balloon only.

The LCPV is a larger vein making complete occlusion more difficult. The RIPV due to its position often requires special catheter manipulation similar to that described by Chun et al. (12). With a RFA catheter there was no significant difference between individual vein isolation rates.

Balloon SizeTrend towards greater isolation rates with the 23mm balloon over the 28mm balloon (96.5% versus 92.6%, p 0.058).

Also found by Van Belle (11) and may be because the smaller balloon ablates further into the vein where more complete contact and more stable positioning can be achieved.

The 23mm balloon seems more prone to causing PNP (10,16), although the difference was not significant in our study.

It may also be less effective at isolating PV ectopy (17) and may lead to more PVS due to ablation in a smaller portion of the vein.

STOP-AF trial (14) had a PVS rate of 3.1% which may have related to long mean procedure duration (371m), repeat procedure rate during blanking of 19% or 23mm balloon use and proceduralist technique.

No symptomatic PVS in our study and no symptomatic or radiographic PVS in four other CBA trials (10-13) which compares favourably to an overall >50% PVS rate of 1.3% in a worldwide survey of RFA (3).

Complications0.93% major complication rate. One patient suffered gastroparesis due to damage to peri-oesophageal vagal plexi by excessive cooling.

Dysphagia and hypomotility occur in around 1% of patients undergoing RFA (18) and studies have shown that transient, reversible thermal lesions may occur in the oesophagus or stomach following CBA as well (19).

There are as yet no published cases of AOF due to CBA but the incidence even with RF is only around 0.03% (20).

Right upper lobectomy.

ComplicationsHeadache, pleuritic chest pain, minor heamoptysis and fluid overload tended to resolve following the procedure or within a week.

There were no major bleeds suggesting performing the procedure on warfarin is appropriate.

Transient PNP occurred in 4.5% and persistent PNP in 3% of patients. One PNP taking 12 months to recover. In five studies using CBA the rate of persistent PNP ranged from 2.5-7.4% (10-14) while in RFA rates are around 0.48% (26) but complete recovery may be less likely.

PNP is often minimally symptomatic and tends to recover early but may persist for 6-12 months and may cause symptoms in those with underlying lung disease.

ComplicationsOne patient had transient partial visual field loss two days following (TIA). The incidence of stroke or TIA following RFA is around 0.4-2% (3, 9).

Several studies on CBA have not reported any incidence of stroke or TIA (10-13.)

cryoenergy is less disruptive to the PV endothelium and leads to less in situ thrombus formation.

STOP-AF trial, however, reported an incidence of stroke/TIA of 4.3% (14) which seems discordant with other studies and may reflect the greater mean procedure duration, greater number of procedures per patient and greater number of CBAs per vein.

Limitations

This was a non-randomised retrospective study that largely used symptomatology to determine freedom from recurrent AF.

This cohort of patients, however, had frequent and highly symptomatic episodes of AF prior to the CBA and the main goal of CBA was relief of symptoms.

Complication rates were also largely assessed by symptoms so it is possible some patients may have experienced an asymptomatic reduction in PV diameter.

Conclusions

CBA achieves freedom from symptomatic AF in 56.7% of paroxysmal and 36.5% of persistent AF patients at two years.

At this time 72.6% of paroxysmal AF patients had ≤2 symptomatic recurrences.

Balloon based catheter technique improves procedural time over RFA and the use of cryoenergy by experienced operators appears to reduce the risk of major complications including PVS, AOF and stroke but with an increased risk of PNP.

References• 1. Fisher JD, Spinelli MA, Mookherjee D et al. Atrial fibrillation ablation: reaching the mainstream. Pacing Clin Electrophysiol. 2006; 29:523-537.

• 2. Papone C, Rosanio S, Augello et al. Mortality, morbidity and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomised long term study. J Am Coll Cardiol 2003; 42:185.

• 3. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Packer D, Skanes A. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation 2005;111:1100-1105.

• 4. Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Balaban K, Pavia SV, Schweikert R, Saliba W, Abdul-Karim A, Pisano E, Fanelli R, Tchou P, Natale A. Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol 2002;40:464-474.

• 5. Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005; 293:2634.

• 6. Pappone C, Augello G, Sala S, et al. A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll Cardiol 2006; 48:2340.

• 7. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991. 22:983.

• 8. Lake RR, Cullen KJ, deKlerk et al. Atrial fibrillation in an elderly population. Aust NZ J Med 1989. 19:321-326.

• 9. Cutlip D. Radiofrequency catheter ablation to prevent recurrent atrial fibrillation In: Basow DS, editors. UpToDate. Waltham, MA. Jan 2011.

• 10. Neumann T, Vogt J and Schumacher B et al. Circumferential Pulmonary Vein Isolation With the Cryoballoon Technique: Results From a Prospective 3-Center Study. J. Am. Coll. Cardiol. 2008;52;273-278.

References• 11.Van Belle Y, Janse P, Rivero-Ayerza MJ, Thornton AS et al. Pulmonary vein isolation using an occluding cryoballoon for circumferential ablation:

feasibility, complications, and short-term outcome. Eur Heart J. 2007 Sep;28(18):2231-7.

• 12. Chun KR, Schmidt B, Metzner A et al. The 'single big cryoballoon' technique for acute pulmonary vein isolation in patients with paroxysmal atrial fibrillation: a prospective observational single centre study. Eur Heart J. 2009 Mar;30(6):636-7.

• 13. Helena Malmborg*, Stefan L Honnerholm, and Carina Blomstr Hom-Lundqvist. Acute and clinical effects of cryoballoon pulmonary vein isolation in patients with symptomatic paroxysmal and persistent atrial fibrillation. Europace (2008) 10, 1277–1280.

• 14. Packer DL, Irwin JM, Champagne J et al. Safety and Effectiveness Trial Evaluated the Arctic Front® Cardiac CryoAblation Catheter System for the Treatment of Paroxysmal Atrial Fibrillation. ACC Atlanta. March 2010.

• 15. Haissaguerre M, Jais P and Shah DC et al. Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins. N Engl J Med. Sep 1998; 339:659-666.

• 16. Kuck KH and Furnkranz A. Cryoballoon Ablation of Atrial Fibrillation. J Cardiovasc Electrophysiol, Vol. 21. 1427-1431, December 2010.

• 17. Arentz. T Weber R and Burkle G et al. Small or large isolation areas around the pulmonary veins for the treatment of atrial fibrillation? Results from a prospective randomized study. Circulation 2007;115:3057-3063.

• 18. Calkins H, Brugada J and Packer DL et al. HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-Up: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation Developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and Approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace 2007;9:335-79.

References• 19. Furnkranz A, Chun KRJ and Metzner A et al. Esophageal Endoscopy Results After Pulmonary Vein Isolation Using the Single Big Cryoballoon Technique. J Cardiovasc

Electrophysiol, Vol. 21 (8). 869-874. Aug 2010.

• 20. Lickfett L. Esophagoscopy following cryoballoon pulmonary vein ablation: Can the promise be met? 10.1016/j.hrthm.2009.04.013. Heart rhythm society.

• 21. Defaye P, Kane A and Chaib A et al. Efficacy and Safety of pulmonary vein isolation by cryoablation for the treatment of paroxysmal and persistent atrial fibrillation. Europace. Mar 2011,

• 22. Gaita F, Leclercq JF and Schumacher B. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: Comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electroophysiol. Mar 2011.

• 23. Nadji G, Hermida JS and Quenum S. Dual balloon size strategy for cryoisolation of the pulmonary veins in patients with atrial fibrillation. Comparison of 23 and 28 mm diameter cryoballoons. Arch Cardiovasc Dis. 2011 Feb;104(2):70-6.

• 24. Thomas D, Katus HA and Voss F. Asymptomatic pulmonary vein stenosis after cryoballoon catheter ablation of paroxysmal atrial fibrillation. J Electrocardiol. 2010.

• 25. Van Belle Y, Janse P and Theuns D et al. One year follow up after cryoballoon isolation of the pulmonary veins in a patient with paroxysmal atrial fibrillation. Europace 2008. 10, 1271-1276.

• 26. Sacher F, Monahan KH and Thomas SP et al. Phrenic Nerve Injury After Atrial Fibrillation Catheter Ablation. J Am Coll Cardiol, 2006; 47:2498-2503 .