Vein of Marshall Ethanol Infusion for Persistent Atrial Fibrillation

Although the risk of stroke is comparable in persistent and paroxysmal AF, the prevalence of
persistent AF increases dramatically with increasing age, and thus is an overall more
significant cause of morbidity and mortality. In the United States, there are currently an
estimated 3.0 million adults with AF, and this number is expected to double in the next 25
years. Hospitalizations with a primary diagnosis of AF are close to half a million per year,
which generates a tremendous economic burden on the health care system. When compared to
health care costs of non-AF control subjects, patients with AF have greater annual healthcare
costs (up to $8705 total annual incremental cost). On the basis of current prevalence data,
it is estimated that AF leads to a national incremental health care cost of up to $26
billion. Inadequacy of pharmacological treatment options for persistent AF Management
strategies are directed at heart rate control and stroke prevention -mere palliation- or at
rhythm control. It has been shown that rhythm control strategies using antiarrhythmic drugs
offer no benefit in elderly patients or patients with heart failure. Most of the lack of
benefit of such rhythm control strategy is thought to be due to the adverse effects and
suboptimal efficacy of antiarrhythmic drugs that can potentially augment mortality. Indeed,
preservation of normal sinus rhythm is associated with decreased mortality. Dronedarone, the
only antiarrhythmic drug shown to improve outcomes in nonpermanent AF compared to placebo,
has been shown to double mortality, stroke and hospitalization for heart failure in the
PALLAS study in patients with permanent. Thus, antiarrhythmic drugs remain suboptimal at best
for the treatment of AF.

Shortcomings of catheter ablation of persistent AF Weak mechanistic rationale: Isolation of
the pulmonary vein (PVs2) and adjacent LA (PV antrum) is the accepted procedural endpoint,
based on the mechanistic concept that atrial extrasystoles arising from the PVs initiate
paroxysmal AF. Other, non-PV triggers have been demonstrated.36 The link between PV extra
systoles and AF is clear in paroxysmal AF, but not in persistent AF, in which the mechanisms
of AF seem to be related more to a chronic atrial substrate than to acute triggers.4 Indeed,
intramural reentry in the posterior LA seems to be particularly relevant in chronic models of
AF. In persistent AF, the procedure has evolved, rather simplistically, to include additional
lesions -besides isolation of the PVs, variably placed in the posterior wall, LA roof, and
towards the mitral annulus, the superior vena cava,44 left atrial appendage, and other areas
where complex fractionated atrial electrograms (CFAE) may be mapped. This brute force
approach of simply destroying more tissue has yielded additional success, but new procedural
targets with solid mechanistic bases are needed.

Suboptimal success and need for repeat procedures. Despite the additional tissue destruction,
ablation success in persistent AF is with much lower than in paroxysmal AF, with single
procedure success reported as low as 27%, 36%, or 49%, but up to 61% or 67%, depending on
study heterogeneities in: definitions of persistent AF and of recurrence of AF, the type of
AF monitoring, and ablation technique and operator experience. In order to achieve overall
acceptable success rates, (which can reach up to 79%-94%), there is a consistent need for
repeat procedures (sometimes up to 4) and the concomitant use of antiarrhythmic drugs. The
rate of repeat procedures in experienced centers can reach up to 70 to 80%.PMF after catheter
ablation of persistent AF. Clinical failures of a first ablation procedure are caused, in a
significant portion of patients, by atrial flutters, rather than recurrent AF, and recurrence
as flutter portends a greater chance of success in a second procedure. Such atrial flutters
may be caused by perimitral reentry in up to 33-60% of the patients. Catheter ablation of PMF
involves the creation of a linear lesion from the mitral annulus to the left inferior PV (the
so-called mitral isthmus).Achieving a complete ablation (defined by bidirectional conduction
block across the ablation line) can be very difficult, with success rates reported as 32%,
64%, or 71%. It sometimes requires ablation inside the coronary sinus (CS), in close
proximity to the circumflex coronary artery, which could be damaged of note, incomplete
ablation of the mitral isthmus is proarrhythmogenic, increasing the risk of recurrent flutter
by up to 4 times.

Inclusion Criteria:

1. Patients between the ages of 21 and 85 years

2. Diagnosed with symptomatic persistent AF Documentation of history of AF for at least 6
months AF not spontaneously converting to sinus rhythm, persisting for ≥7 days Sinus
rhythm after cardioversion is NOT exclusion, provided that≥2 episodes of persistent AF
occurred in the previous 6 months

3. Resistant or intolerant to at least one class I, II, or III anti arrhythmic drugs
(AAD)

4. Patients deemed candidates for radio frequency(RF) ablation of AF

5. Able and willing to comply with pre-, post-, and follow-up requirements.

Exclusion Criteria:

1. Patients with previous PVAI procedure or left heart ablation procedure.

2. Left atrial thrombus.

3. LA diameter greater than 65 mm on long axis parasternal view, or left atrial volume
more than 200 cc by MRI or CT.

4. Left ventricular ejection fraction < 30%.

5. Cardiac surgery within the previous 180 days.

6. Expecting cardiac transplantation or other cardiac surgery within 180 days.

7. Coronary percutaneous transluminal coronary angioplasty (PTCA)/stenting within the
previous 90 days.

8. Documented history of a thrombi-embolic event within the previous 90 days.

9. Diagnosed atrial myxoma.

10. Significant restrictive, constrictive, or chronic obstructive pulmonary disease with
chronic symptoms.

11. Significant congenital anomaly or medical problem that in the opinion of the
investigator would preclude enrollment

12. Women who are pregnant.

13. Acute illness or active infection at time of index procedure documented by either
pain, fever, drainage, positive culture and/or leukocytosis (WBC > 11. 000 mm3) for
which antibiotics have been or will be prescribed.

14. Creatinine> 2. 5 mg/dl (or > 221 μmol/L, except for patients in dialysis).

15. Unstable angina.

16. Myocardial infarction within the previous 60 days.

17. History of blood clotting or bleeding abnormalities.

18. Contraindication to anticoagulation.

19. Contraindication to computed tomography or MRI procedures.

20. Life expectancy less than 1 year.

21. Uncontrolled heart failure.

22. Presence of an intramural thrombus, tumor, or other abnormality that precludes
catheter introduction or positioning.

23. Presence of a condition that precludes vascular access.

24. Institute for Natural Resources (INR) greater than 3. 5 within 24 hours of procedure.

25. Cannot be removed from antiarrhythmic drugs for reasons other than AF.

26. Unwilling or unable to provide informed consent.

27. Current reported alcoholism.