Eur J Cardiothorac Surg 2003;24:731-740
© 2003 Elsevier Science NL
Cryoablation of the left posterior atrial wall: 95 patients and 3 years of mean follow-up
Eric Manassea*,
Fiorenzo Gaitab,
Simone Ghisellia,
Alessandro Barbonea,
Lucia Garberogliob,
Enrico Citterioa,
Diego Ornaghia,
Roberto Gallottia
a Department of Cardiac Surgery, Istituto Clinico Humanitas, Via Manzoni 56, Rozzano, Milano, Italy
b Department of Cardiology, Ospedale di Asti, Asti, Italy
Received 23 December 2002;
received in revised form 25 July 2003;
accepted 27 July 2003.
* Corresponding author. Tel.: +39-338-8115422; fax: +39-2-659-6205
e-mail: ericmana03{at}yahoo.it
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Abstract
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Objective: Endocardial ablation of the left atrial posterior wall has been used to treat atrial fibrillation. Aim of the study was to evaluate its efficacy looking for the ablation pattern allowing a fast execution with limited interference on atrial contractility. Moreover a statistical analysis to identify predictors of long-term sinus rhythm recovery has been provided. Methods: From April 1998 to May 2002, 95 patients with permanent (mean duration 65 months) or persistent (33%) atrial fibrillation have undergone three different ablation patterns, only 1 patient being affected by lone atrial fibrillation. Mean antero-posterior left atrial diameter was 76.2 mm. The prospective study collected information regarding variables related to patients’ demographics, disease's characteristics and type of surgical ablation employed. Dependent variables were presence of sinus rhythm either at discharge and at 6 months. A logistic regression analysis was used to estimate the association between the collected variables and sinus rhythm restoration. Results: In-hospital and late mortality rate were 3.2 and 6.3% respectively. At discharge 67 patients (72.8%) were in sinus rhythm while at a mean follow-up of 3 years, 81.4% of 86 surviving patients are in sinus rhythm. Major adverse events rate including cardiac reoperation, pace-maker implantation and cerebrovascular accident were 8.5, 6.3 and 4.2%, respectively. Pre-operative atrial fibrillation duration, left atrial dimension and type of mitral disease did not show any correlation with long term success while the lesion pattern and the rhythm at discharge were significant predictive factors. Survival is significantly higher in patients who converted to sinus rhythm at discharge (P=0.014) with respect to those who remained in atrial fibrillation. Conclusions: Permanent and persistent atrial fibrillation associated to a major cardiac disease can be safely treated with a linear ablation of the left atrial posterior wall. Satisfactory results in terms of rhythm restoration may be achieved regardless of the duration of the arrhythmia and its effects on atrial diameter. Any effort should be prompted to discharge patients in sinus rhythm. Life expectancy is longer if sinus rhythm is restored.
Key Words: Cryo • Ablation • Atrial fibrillation • Arrhythmia • Surgery • Endocardial • Cardiac
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1. Introduction
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Atrial fibrillation (AF) is a highly common arrhythmia with a relevant burden: mortality and morbidity increase though it is classified as benign. Its prevalence doubles each decade, reaching almost 9% at age 80–89 [1]. Patients with ‘chronic’ AF are usually better adapted than ‘paroxysmal’ AF, but the majority complain of exercise limitation, dyspnea on exertion and fatigability finally interfering with their normal lifestyle and job capacity. Loss of synchronous atrio-ventricular contraction and blood stasis are among the mechanisms responsible for the symptomatology. Poorer survival rates of AF patients compared with sinus rhythm (SR) people have been documented in the general population and also after surgery [2]. AF carries an important burden also when appearing only post-operatively as shown in the CASS registry: those with AF had a 5-year stroke risk of 22.5% as compared with 6.9% for those without [3]. The attributable risk for stroke associated with AF increases steeply with age up to 23.5% at age 80–89. AF is present in approximately 50% of patients undergoing surgery for mitral valve disease. Surgery of AF has developed through the years and different tools and ablation patterns continue to appear showing the problem is far from being definitively solved. Cryoablation effects on the heart were first described by Hass [4]. The mechanism of cryogenic tissue injury might be mitochondrial dysfunction followed by edema and cell necrosis, though other mechanisms have been proposed [5]. Extensive studies have already documented that cryosurgery has no short or long-term adverse effects on the vascular structures. Previous studies have identified different pre and operative predictors of success, as for left atrial systolic dimension correlating with SR restoration [6] while pre-operative AF duration correlated with atrial function recovery [7]. Others found a prognostic favourable correlation when mitral regurgitation was the prevalent mitral disease [8] or when there was not any need for associated tricuspid valve plasty [9]. With this study we wished to identify pre and peri-operative predictive factors of sinus rhythm restoration and get insights on the relative efficacy of different ablation patterns.
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2. Methods
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2.1. Study design and patient selection
This study was planned as a prospective cohort study. All patients presenting with permanent AF (PMAF) or persistent AF (PSAF) were enrolled in the study. PMAF was defined as continuous AF, not susceptible to cardioversion, lasting for more than 6 months pre-operatively. PSAF was defined as AF lasting for more than 6 months pre-operatively but transiently cardiovertible or lasting less than 6 months in presence of severely disabling symptomatology in spite of medical therapy and/or electrical cardioversion attempts. Patients with very depressed low ejection fraction (<25%) were excluded so as not to prolong the ischemic clamping time strictly necessary for the main surgical procedure. An informed consent was obtained by all patients prior to surgery. Data from four different categories were collected for each patient. Among patient's demographics: age, sex, type of AF, AF duration, coexistence of mitral disease and its functional classification, mean antero-posterior (A-P) left atrial diameter. Among surgical data: ablation pattern and need for tricuspid valve plasty. Need for electrical or pharmacological cardioversion and rhythm at discharge were chosen among the immediate post-operative course data. Finally among the follow-up data the following were collected: rhythm at discharge, at 6 months and at end of follow-up, need for prolonged antiarrhythmic therapy (>6 months), electrical cardioversion, transient arrhythmias and complain of palpitation, echocardiographic evaluation of A-P left atrial diameter.
2.2. Surgical technique
All operations were performed at the same institution by different surgeons, under routine cardiopulmonary bypass with double venous cannulation and moderate hypothermia. The left appendage was externally ligated when present. Once the left atrium was opened through a paraseptal incision after cold cardioplegic arrest, the ablation was started. A dual-probe cryosurgical system (Frigitronics, Cooper Surgical, Shelton, Connecticut) was used maintaining the nitrous oxide (N2O) pressure in the cylinders above 720 pounds per square inch; applications of 2 min (3 min between the inferior left pulmonary vein and the posterior mitral leaflet (PML) at -60°C were obtained using two probes simultaneously to avoid any gap and reduce the overall application time. The probe was applied on the external border of the pulmonary veins. The rest of the operation was carried out routinely once the ablation was completed.
2.3. Ablation pattern
At the beginning of our experience the ablation pattern was meant to isolate the posterior left atrial wall as a whole (figure of ‘A’): the four pulmonary veins box (4PVB) was connected to the PML (segments P1 and P3) with two parallel tracts to increase the chances of effective electrical block where the atrial wall is more thick. Then the two inferior pulmonary veins were no longer connected to each other in order to spare time (figure of ‘inverted U’). The following step was meant to reduce by almost 50% the dimension of the excluded akinetic area by connecting the 4PVB to the mitral anulus with one single tract (‘Rugby’ figure). The natural evolution of this concept was to isolate the 4PV orifices separately but discouraging short-term results forced us to the final and actual step: a figure of ‘7’ (Fig. 1)
. The ablation patterns defined as A-U-Rugby have all in common the exclusion of the 4PVB and hence are herewith defined as ‘closed techniques’. The ‘4PV’ pattern consisted of four focal applications. The "7" pattern is represented by a continuous line connecting the four pulmonary vein orifices and the mitral anulus without excluding any area and is hence herewith defined as ‘open technique’.
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Fig. 1. Internal view of the posterior aspect of the left atrium. Evolution of the ablation pattern from ‘A’ figure to ‘inverted U’ and successively to ‘rugby’ figure eliminating respectively tracts 1 or 2 (so called ‘closed techniques’); avoiding both tracts (1 and 2) lead to ‘7’ figure (defined as ‘open technique’). Four pulmonary veins technique consisted of four focal applications PVs’ orifices. LAA, left atrial appendage; and MPL, mitral posterior leaflet.
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2.4. Pharmacological protocol
Intra-operative direct cardioversion was performed in all patients with AF after weaning from bypass, when amiodarone i.v. infusion (600 mg/250 at 20 ml/h) was started regardless of the rhythm and heart rate. On the 2nd post-operative day, amiodarone oral administration was started (200 mg twice a day) unless propafenone was preferred because of the presence of disthyroidism. An electrical or pharmacological cardioversion was always attempted before discharge if AF or atrial flutter (AFF) were present. Withdrawal of antiarrhythmic therapy 3–6 months post-operatively, was suggested to the referring doctor in the absence of AF-AFF recurrence while oral anticoagulation therapy (OAT) could be withdrawn in the absence of a mechanical prosthesis already at 3 months.
2.5. Follow-up
Data were collected through outpatient visit, by routine ECG and/or echocardiography at 1, 6, 12 months and once a year, unless the presence of symptoms required differently, by ECG examination and telephone contact with both the patient and the referring physician. Should a patient have reported palpitations or general discomfort, it would have been assumed as having had supraventricular arrhythmias though in the absence of an ECG recording. Echocardiographic examinations were conducted with the patient in the left lateral supine position using commercially available ultrasonographic systems (Acuson, Sequoia and Aspen, Mountain View, CA). Apart from the usual morphological evaluation the following parameters were determined: left atrial A-P diameter in the parasternal long-axis view in accordance with standard recommendations and ejection fraction derived from the standard equation. All the parameters were obtained according to the guidelines of the American Society of Echocardiography. Trans-mitral and trans-tricuspid flow velocities measured by transthoracic-pulsed Doppler echocardiography from an apical four chamber-view with the sample volume positioned between the tips of the mitral and tricuspid leaflets during diastole; peak velocities of the early filling (E) wave and atrial contraction (A) wave were determined.
2.6. Statistical analysis
The analysis was focused on the followings: describing the basal characteristics of the enrolled patients; estimating the association between rhythm at discharge and demographic characteristics or ablation pattern; verifying the association between permanence in rhythm at 6 months and demographic characteristics, ablation pattern or rhythm at discharge; describing the probability of remaining in rhythm during the follow-up.
The description of the basal characteristic of the sample was made using summary statistical measures. Frequencies and percentages were used for categorical data while mean and standard deviation were chosen for continuous data. 
2 test and analysis of variance analysis when appropriate were used for comparison of the distribution of categorical and continuous variables among surgical patterns.
Analysis of the relationship between SR restoration, either at discharge and at 6 months, and the parameters considered as possible prognostic factors was made with a univariate logistic regression model. This analysis was repeated for SR presence at discharge and at 6 months, evaluating the prognostic role of immediate success. The same variables were considered in the multivariate logistic regression model if the p value was less than a chosen cut-off of 5%. Probability of permanence in SR over time and overall survival rate were calculated with Kaplan–Meier curves and compared with the log-rank test. All the analysis were made with the program Stata6 (http://www.stata.com).
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3. Results
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3.1. Population
From April 1998 to May 2002 at the Istituto Clinico Humanitas, endocardial cryoablation of the left atrial posterior wall was used in 95 consecutive patients to treat AF. Demographics are listed in Table 1. According to the ablation pattern employed. The distribution of the considered variables was similar in the three groups, except for the A-P left atrial diameter and the necessity for associated tricuspid valve plasty. In fact ‘4PV’ and ‘7’ figures were used more frequently in patients with smaller atria and more often when the tricuspidalization was severe enough to require a plasty. The majority of patients were in advanced New York Heart Association (N.Y.H.A.) Class. We treated either PMAF or PSAF; AF was lasting for more than 60 months in 43.5% of patients. All patients but 2, who had lone AF (LAF) and coronary disease respectively, were primarily referred for valvular disease, most often the mitral valve (70.5%). Lone aortic or tricuspid valvular disease were present in 6.3 and 1.1%, respectively, while complex valvular disease was present in 17.9% of patients. Intra-operative and post-operative data are provided in Tables 2 and 3. The slightly elongated cardiopulmonary bypass and aortic cross-clamp time reflect the procedural time of the cryoablation (15–20 min). Limited surgical exposure, as for right mini-thoracotomies, was not a contraindication. Mean length of stay was only mildly elongated in comparison to our standards reflecting the time required to prepare patients for the electrical cardioversion.
3.2. Mortality
Follow up is 100% complete, median time of follow-up is 36 months, ranging from 6 to 54 months. (Table 3). Overall crude mortality rate was 9/95 (9.4%). There were three in-hospital deaths (3.1%). There was one operative death due to tear of the posterior left atrial wall as a consequence of retracting the cryo-probe before thawing was completed. One patient died 1 month after the operation, in stable SR, because of septicemia. Another patient, in AF, died 49 days after the operation because of pneumonia. Among the 92 discharged patients there were six late deaths (6.5%), five being on AF: two patients at 8 and 45 months, one being on OAT, because of stroke; one patient at 3 months because of cardiac heart failure; one patient at 14 months, who needed intra-aortic balloon support and dialysis in the immediate postopertaive course, for intercurrent septicemia; one patient at 39 months for cerebral cancer. One patient submitted to an aortic valve replacement with a bioprosthesis, died in SR at 6 months because of stroke. Most frequent mode of death in our series is stroke.
3.3. Morbidity
3.3.1. Major cardiac reoperation
Among the 94 patients surviving the intervention, eight patients (8.5%) needed a major re-intervention. Three patients (3.1%) required early re-operation: two patients, respectively on 1st and 6th post-operative day, because of mitral valve plasty (MVP) failure; one patient on 6th post-operative day for peri-valvular leak in a redo mitral valve replacement. Five patients required late reoperation (5.3%) from 2 to 30 months after the operation: three patients because of MVP failure and two patients because of peri-valvular leak in a mitral valve replacement (MVR). The overall feature of 3.1% of peri-valvular leak is approximately the same of the non-cryo surgery population at our institution, therefore we may assume it not to be related to the arrhythmic procedure itself.
3.3.2. Minor reoperation
Two patients (2.1%) were reopened on 1st post-operative day because of bleeding not related to the ablation procedure.
3.3.3. Pacemaker implant
Among the 94 patients surviving the intervention, six patients (6.3%) needed a pace-maker implant, four of whom during hospitalization. Three patients submitted to a MVR and one patient to an aortic valve replacement (AVR) required pacemaker implant (3.1%) because of 3° atrio-ventricular block in three patients and sick-sinus-syndrome in one patient. The ablation pattern was respectively ‘4PV’ in one patient, ‘A’ in two patients and ‘7’ in one patient. Two patients required PM implant after discharge (2.2%): both of them had been submitted to MVR while the ablation pattern were ‘A’ and ‘7’, respectively.
3.3.4. Cerebrovascular accident
Overall cerebrovascular accident rate, including stroke and transient ischemic attack, was 4/94 (4.2%). One patient (1.1%), who had undergone a MVR, experienced a transient ischaemic attack resolved before discharge. Three patients (3.1%) experienced a lethal stroke at 7, 8 and 45 months, respectively. Two of them were on OAT because of the persistence of AF: they had undergone a coronary bypass and a bioprosthetic AVR respectively while the ablation pattern employed were ‘U’ and ‘4PV’, respectively. The third patient, in SR, had a bioprosthetic AVR with an ‘A’ figure.
3.3.5. Rhythm
3.3.5.1. Hospital rhythm
Fourty-two patients (44.2%) had undergone at least one electrical or pharmacologycal cardioversion before discharge. The N.Y.H.A. functional class improved in 62.6% of patients. Sixty-seven patients (72.8%) were discharged in SR.
The results of the univariate analysis are presented in Table 4. The only factor that was significative, with a level of 5%, was age. The risk of failure, defined as absence of SR at discharge, increases with age. Since this was the only relevant factor, a multivariate analysis was not performed.
3.3.5.2. Six months rhythm
The results of the univariate and multivariate logistical regression analysis are shown in Table 5. The risk of failure, defined as absence of SR at 6 months, increases with aging and presence of AF at discharge. Among ablation patterns, ‘4PV’ was associated to a worse prognosis (Fig. 2A)
. In the multivariate analysis the ablation patterns and presence of AF at discharge were the only independent prognostic factors of failure. Though statistical significance was not reached, a trend was observed when comparing the type of AF with respect to the presence of SR at end of follow-up: 59% (PMAF) and 39% (PSAF) either experienced transient supraventricular arrhythmias and/or palpitations or were on antiarrhythmic drugs. This result confirmed previous observations that permanent AF patients may reach the same results of the persistent AF patients at the cost of greater pharmacological requirements and more irregular course [10].
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Fig. 2. (A) Kaplan–Meier curve: probability of remaining free of supra-ventricular arrhythmias and/or palpitations according to the ablation pattern. (B) Survival according to rhythm at discharge.
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No evidence of association between preoperative duration of AF and SR status at 6 months was detected.
3.3.5.3. Rhythm at the end of follow-up
Fourty-two patients (44.2%) had undergone at least one electrical or pharmacologycal cardioversion before discharge. The N.Y.H.A. functional class improved in 62.6% of patients. Sixty-seven patients (72.8%) were discharged in SR. At the end of follow-up nine patients (13.4%), among those discharged in SR, present in AF; while 13 patients (52%) over 25 discharged in AF, are on SR. At a mean follow-up of 1091.4 days, 70 patients (81.4%) among 86 surviving, are in SR. Among patients in SR, 19 (27.1%) are still on antiarrhythmic therapy. A cardioversion, electrical and/or pharmacologycal, was necessary in nine patients (12.9%) of this cohort. In two patients (2.9%), among those submitted to a non-fluoroscopic navigation system (CARTO, Biosense, Webster), a radiofrequency ablation procedure performed in the presence of left atrial flutter due to a gap in the surgical ablation line, was successful in restoring stable SR. These early recurrences are also described by interventional electrophysiologists in 35% of patients within 2 weeks of catheter ablation and are associated with lower long-term success rate [11]. Thirty-two patients (45.7%) though being on SR, have experienced transient arrhythmias or complained of palpitations during the follow-up. The Kaplan–Meier AF-free curve splitted by treatment group, showed similar results to the analysis of 6 months rhythm, although the conventional statistical significance was not reached in this analysis: the likelihood of remaining continuously free of AF was worse in the ‘4PV’ than in the other two techniques: at 6 months (and 1 year) the probability of remaining free were 90.4 (72.7), 90.5 (90.5) and 97.4 (92.02) for the ‘4PV’, ‘7’ and ‘closed techniques’, respectively. Among patients on SR, 15 (18.5%) are still on OAT though not having a mechanical prosthesis, in two patients being related to pre-operative systemic embolization episodes.
Fig. 2B shows the relationship between the presence of SR rhythm at discharge and mortality, suggesting a clear association between long term prognosis and restoration of SR.
Table 6 describes the relationship between rhythm at end of follow-up and mortality, taking into consideration also patients who switched from AF to SR and conversely over time. A significant higher mortality is associated to patients who permanently persisted on AF with respect to those who converted to SR either definitely or temporarily.
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Table 6. Survival according to rhythm at the end of follow-up; it takes into consideration possible groups’ cross-over
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3.3.6. Atrial contractility
Though all patients have undergone an echocardiographic examination before discharge only 45 patients, among those on SR, have been visited at our outpatient echocardiography clinic laboratory between 3 and 9 months post-operatively. In fact not all patients were available due to the fact that they had been referred from another region. Over 80% showed bi-atrial activity as demonstrated by the presence of a valid trans-mitral and/or tricuspid A wave (>0.3 m/s) at the trans-thoracic examination.
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4. Discussion
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The social and individual impact of AF is well known. In fact patients may require several hospitalizations to control high ventricular response [12] or to treat symptoms related to congestive heart failure and finally may become severely disabled because of the discomfort related to heart rate variations or as a result of its most threatened complication, thromboembolism. Neither oral anticoagulation therapy is without risk for cerebrovascular accidents, especially at the beginning of the treatment and in older patients. AF patients have a mortality rate about twice that of age and sex matched individuals without AF, and a stroke rate 5-fold greater increasing up to 18-fold if AF is associated to rheumatic mitral disease. These data are consistent with our experience: 50% of late deaths are related to a stroke. Patients presenting with LAF associated to a major risk factor (>65 years-diabetes-hypertension-previous cerebrovascular accident-heart failure) have an annual risk of stroke of 4% or greater. Principal source of thromboembolism is localized to the left atrial appendage (LAA) in 91% of patients with LAF as compared to 57% of patients with associated rheumatic disease [13]. For these reasons the main goal of surgery should be to prevent future thromboembolic events. With this regard, exclusion of the left atrial appendage should always be considered as an essential part of any ablation technique [14]. Persistent AF should be considered with caution too because of its tendency to develop as permanent AF [15]. In our study the type of presenting AF was not an independent predictive factor though permanent AF patients experienced arrhythmias and needed therapy more frequently than persistent AF patients. We decided to treat those patients presenting with AF as an associated cardiac disease, one single patient with LAF being enrolled because of his willingness to refuse any other treatment but surgery. There have been reported better results treating lone atrial fibrillation, with respect to AF as an associated condition [14]. These promising data have forced us to work out also a thoracoscopic approach together with new ablation tools to treat expressly LAF patients [16]. Several surgical techniques had been proposed so far to treat AF. Some of them focused on the ‘critical mass’ concept while more recently particular attention was given to the ‘trigger foci’ theory [17,18]. The hypothesis of the surgical maze procedure was the elimination of all hypothetical bi-atrial re-entrant circuits realized by multiple incisions, amputation of appendages and PVs isolation aiming at a critical mass reduction (i.e. reducing the mass of electrically continuous atria below the critical threshold required for AF maintenance); finally the sinus impulse was directed from the sino-atrial node to the atrioventricular node along a specified route. Subsequently the concept of creating linear lesion lines to modify the substrate responsible for maintaining the arrhythmia was adopted by interventional electrophysiologists. Probably both strategies are correct: the first applies to the maintenance of AF while the second to its origin since AF requires triggers for initiation, a favourable substrate for maintenance and probably a favourable autonomic tone too. Because of the presence of a transition zone between the PVs’ endotelium and the left atrial endocardium, this area represents the proper substrate for micro re-entry development leading to premature atrial beats which may stimulate the atria in such a manner that macro re-entry circuits are set-up and become self-perpetuating [15]. Hence in our view, a combination of both techniques would offer greater likelihood of stable SR restoration. Consensus is still lacking regarding the necessity of a bi-atrial approach. Apparently the left atrium is the driving chamber for AF, at least when mitral valve disease is associated [19]. In consideration of the fact that the left posterior wall and the pulmonary vein orifices are involved in almost all of the approaches so far proposed by surgeons and electrophysiologists, we limited our ablation to the left atrium. There was already strong evidence that surgical ablation of the PVs region could be effective in the treatment of AF [20] and that a left atrial maze could be as effective as a bi-atrial procedure in restoring SR [21]. Clinical and sperimental works had proven left atrial lesions could obtain favourable results in the treatment of AF [22]. In fact an ablation of this region has a dual effect: the isolation of the trigger foci acts on the genesis of AF while the modification of the substrate acts on its maintenance. Due to its simplicity and reproducibility the design proposed by Sueda appeared to us most appealing. Replacing all the knife incisions with cryoablation applications would make the procedure safer and faster. Indeed cryoablation allows to replace ‘cut and sew’ sparing much cross-clamp time and reducing the risk of hemorrhage. The transmurality of cryolesions applied either endo or epicardially, has already been assessed, though their lack of consensus on whether this is essential or not [14]. Yet the ablation pattern remained to be established. Our goal was to develop a linear lesion as effective as possible in terminating AF. At the same time it needed to fulfill two requirements: it should be as short as possible to reduce the ischemic time and should also avoid any intrinsic limitation to atrial contractility. Given the worse immediate results obtained with the ‘4PV’ technique, this was immediately abandoned. The evolution from the ‘closed techniques’ to the open figure of ‘7’, which meets these requisites, appeared natural. Compared to ‘4PV’ pattern, these patterns showed equally better: the ‘closed techniques’ and the ‘7’ figure having been employed respectively more often with larger left atria and tricuspidalization of the mitral disease. Since the majority of patients were valvular, mostly mitral, we used an endocardial approach while the left atrium was already accessible. Applications of 2 min were used all along the ablation course but from the left inferior pulmonary vein to the PMA, where 3 min were used instead. In fact the first electrophysiological control studies performed at the beginning of our experience, revealed this tract to be at jeopardy for residual gaps, probably due its thickness. Should a gap be present between the pulmonary veins and the mitral anulus, left atrial flutter may present. Cox claimed it was essential to block all electrical conduction along the inferior portion of the left atrium between the inferior pulmonary vein orifices and the PMA, otherwise the continuity of the left atrium and septum could theoretically sustain long reentrant circuits responsible for atrial flutter. Eventually even though this region was completely divided, the electrical conduction among the atria could still propagate along the coronary sinus [23]. Anyway it may be speculated that in presence of a gap, interventional radiofrequency ablation should complete the ablation line quite easily. Furthermore, it appeared to us that when the ablation procedure was not sufficient in itself to terminate atrial fibrillation, electrical or pharmacologycal cardioversion became however more efficacious due to the modified substrate. The actuarial free of AF recurrence curve shows that at any given time interval worst results were achieved by the ‘4PV’ technique. Posterior left atrial stasis has been shown to be as important as appendage stasis for the risk of stroke, its risk being quantitatively related to the degree and becoming substantial with an atrial velocity <15 cm/s. Unfortunately transthoracic echocardiographic data seem to offer limited specificity [24]. Nevertheless other authors demonstrated that as long as there is right atrial-to-right ventricular synchrony and preserved right atrial function, the forward cardiac output is normal regardless of whether the left atrium is contracting [25]. We paid great attention towards preservation of left posterior atrial contractility though it may be speculated that contribution of this area to the whole atrial pump function may be naturally limited by the ‘anchor effect’ of the pulmonary veins. Magnetic resonance imaging visualization has shown that the roof of left atrium is the part that moves the least [14]. In either two of the more successful ablation patterns we propose, the entire atrial myocardium is still electrically activated, except for the pulmonary veins box and left atrial appendage, thus preserving an adequate postoperative atrial transport function. Longstanding pre-operative AF duration, huge left atrial dimension and right atrial involvement did not represent a contraindication in our experience, in evident contrast to published recommendations. It could be objected that in spite of SR restoration, a highly dilated and thin walled left atrium would not be able to reduce its dimension and regain a proper contractility with time. Though we may agree from a theoretical point of view, this was not our own experience as shown by the serial echocardiographic evaluation performed in more than half of our SR patients. When comparing mitral to non-mitral patients it appeared to be no correlation with long-term success, as well as when considering the tricuspidalization of the mitral disease. In contrast to previous data patients affected by prevalent mitral regurgitation did not show any difference with respect to patients with prevalent mitral stenosis [8]. Unfortunately, since different surgeons were involved, the analysis of the valvular etiology was not standardized and therefore its’ influence could not be analyzed. It is routine at our institution to treat aggressively post-operative AF and these patients made no exception. Therefore if electrolyte balance and antiarrhythmics drug infusion were not enough to re-establish SR, an external electrical cardioversion was always attempted before discharge. When longer follow-up then revealed this to be the strongest peri-operative predictor factor of long-term success, our policy became even more aggressive. In fact long-term success was clearly related to discharge rhythm regardless of the fact that SR was achieved with an electrical or pharmacologycal cardioversion, while there was no difference among SR patients with or without cardioversion. When all the surviving patients reached at least 6 months of follow-up, the time gap usually considered necessary for the atrial remodelling to complete, a more accurate analysis of different patterns employed could be done. The ‘closed technique’ and ‘7’ figure gave equally better results than the "4PV" technique though this result may reflect only a trend due to the lower number of patients enrolled in this third subgroup. We wish to struggle that our analysis is based on the lesion pattern that was performed at the time of surgery which may not represent the lesion effectively achieved. In other words for many reasons there may still be present some gaps in the ablation line transforming a theoretical ‘inverted U’ lesion in a real ‘7’ figure. Many factors could play a role, among others: malpositioning of the probe, insufficient cylinder pressure, reduced time of exposure and thicker wall. Therefore further and complete electrophysiological study should be warranted before misleading interpretations are given. Nevertheless in our opinion this study deserves attention because of multiple reasons: it is prospectic, a large number of patients has been enrolled, follow-up is 100% complete. New insights have been showed: a clear relationship between sinus rhythm restoration and survival, lack of predictive value of the most commonly recognized preoperative ‘prognostic factors’, relevance of the rhythm at discharge as the strongest predictive factor of long-term success (Fig. 2B).
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5. Conclusion
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Limited cryoablation of the posterior wall of the left atrium is effective in treating AF, both permanent and persistent. Satisfactory long-term results have been achieved in terms of stable regular rhythm restoration despite of pre-operative long-ongoing AF and large atrial chambers. The functional class and the actuarial survival rate improved dramatically when SR was recovered. It is conceivable now to broaden indications in two particular subsets of patients: valvular patients may be considered for more aggressive and earlier treatment at a time when a plasty is still feasible and LAF patients may take advantage of new thoracoscopic approaches.
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6. Study limitations
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Our study carries the bias that the ablation pattern was not randomly assigned but followed a natural chronological evolution which, for ethical reasons, could not be disregarded. Another limitation is represented by the number of patients who could be re-evaluated echocardiographically at our institution.
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Acknowledgments
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I wish to express all my gratitude to Dr Valter Torri (Biometry Unit, Istituto Mario Negri, Milan, Italy) and Emanuela Morenghi (Department of Biometry, Istituto Clinico Humanitas) and Dr Ugo La Marchesina (Echocardiography Department, Istituto Clinico Humanitas) for their invaluable work and suggestions.
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Abstract
1. Introduction
