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Purpose: : There is a significant association between gram-positive bacteria and filamentous fungi that cause keratitis and poly-infections are frequent in these patients 1. In the early stage of the disease, these treatments can change the course of the infection. The aim of this work was to evaluate in vitro the effect of acyclovir ACV in bacterial and fungal coculture treated with antibiotics and antifungal drugs. Methods: : Bacterial and fungal from patients with keratitis were isolated and identified. Cocultures were performed between Fusarium oxysporum and Aspergillus fumigatus with S. Results: : Acyclovir decreased dramatically the growth of Fusarium oxysporum and Aspergillus fumigatus , this activity was affected by the association between Fusarium oxysporum and Aspergillus fumigatus with S aureus or S epidermidis as well as quinolone-antifungal combination except for the combination natamycin-quinolones. The antifungal activity of ACV is affected depending on the combination antifungal-quinolone and the bacterial species in the coculture. Purchase this article with an account. Alerts User Alerts. You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account. This feature is available to authenticated users only. Get Citation Citation. Get Permissions. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication. View Metrics. Forgot password? To View More Create an Account or Subscribe Now. You must be signed into an individual account to use this feature. This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.

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Context Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation AF. Pulmonary vein isolation PVI with radiofrequency ablation may cure AF, obviating the need for antiarrhythmic drugs and anticoagulation. Design, Setting, and Participants A multicenter prospective randomized study conducted from December 31, , to July 1, , of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs. Results Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up. At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey. There were no thromboembolic events in either group. Conclusion Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF. Larger studies are needed to confirm its safety and efficacy. Atrial fibrillation AF , which affects approximately 2 million people in the United States, is a major cause of stroke, adversely impacts quality of life, and is associated with increased mortality. Recently presented data from a study involving patients who had previously not responded to antiarrhythmic drug therapy suggests that patients who received catheter-based AF ablation had significantly less AF during follow-up than those who received further antiarrhythmic drug therapy. We conducted a multicenter prospective randomized pilot study. At the time our study was initiated, there were no consistent data about the success rates of PVI in the medical literature. Therefore, enrollment for our trial was open for 6 months regardless of the sample size obtained during that period. Patients were eligible to enter the study if they had experienced monthly symptomatic AF episodes for at least 3 months. Exclusion criteria were age younger than 18 years and older than 75 years, previous history of atrial flutter or AF ablation, previous history of open-heart surgery, previous treatment with antiarrhythmic drugs, and contraindication to long-term anticoagulation treatment. Each patient signed a written informed consent after approval by the institutional ethics and review board committees at each of the corresponding hospitals. Patients were not randomized to a rate-control strategy because, at the time the study was initiated, a rate-control strategy had not been shown to be as effective as a rhythm-control strategy. Physicians providing patient care were advised to keep patients in the same treatment group during the 1-year follow-up period. All patients underwent 3 preenrollment hour Holter monitoring studies. The primary end point of the study was any recurrence of symptomatic AF or asymptomatic AF lasting longer than 15 seconds during Holter or event monitoring in the 1-year follow-up period. Secondary end points included hospitalization rate during the 1-year follow-up and quality of life as assessed using the Medical Outcomes Study item Short-Form health survey Short-Form The physician providing patient care chose the drug used in the antiarrhythmic drug study group. Each study center was advised to use the maximum tolerable dose of each antiarrhythmic drug. An effort was made to use amiodarone only after the patient failed at least 2 antiarrhythmic drugs. The initiation of class I antiarrhythmic agents was conducted on an outpatient basis, while class III agents were administered in-hospital. The recommended medical regimen consisted of oral flecainide mg twice daily, propafenone mg 3 times daily, and sotalol mg twice daily. For patients not already receiving warfarin, anticoagulation with warfarin was initiated and maintained throughout the study in all patients enrolled in the antiarrhythmic drug group with a target international normalized ratio of 2 to 3. Patients were brought to the electrophysiologic laboratory in a fasting, nonsedated state. A multipolar mapping catheter was placed into the coronary sinus via the right internal jugular vein to record right atrial and coronary sinus electrograms. The ablation catheter and circular mapping catheter were placed via the right femoral vein to the left atrium using a double transseptal puncture technique. In addition, PVI was performed by using phased-array intracardiac echocardiographic monitoring with an intracardiac echocardiographic catheter introduced to the right atrium via the left femoral vein. When a scattered microbubble pattern was observed, energy was titrated down in 5-W increments until microbubble generation subsided. Energy delivery was terminated immediately when a brisk shower of dense microbubbles was observed. Intravenous heparin was administered to achieve an activated clotting time of to seconds. Radiofrequency ablation was performed wherever pulmonary vein potentials were recorded around the pulmonary vein antra. The end point of ablation was complete electrical disconnection of the pulmonary vein antrum from the left atrium. This was considered achieved when no pulmonary vein potentials could be recorded along the antrum or inside the vein by the circular mapping catheter, or if there was electrical dissociation of the pulmonary vein from the left atrium. At the end of the procedure, all 4 pulmonary venous antra were extensively remapped with the circular mapping catheter to check for any persisting pulmonary vein potentials and, if necessary, further ablation was performed to eliminate these potentials. All 4 pulmonary veins were isolated. Neurological checks were performed intermittently during the procedure, at the end of the procedure, and the following day just before discharge. Anticoagulation with warfarin was initiated on the evening of the PVI procedure and continued for at least 3 months with a target international normalized ratio of 2 to 3. Follow-up was scheduled at 1, 3, 6, and 12 months. A loop event-recorder, which was worn for 1 month, was used in all patients to monitor events during the first month and was repeated at 3 months. During the monitoring period, patients were asked to record when they experienced symptoms and 2 to 3 times daily, even if they were asymptomatic. Additional event-recorder monitoring was obtained after the 3-month period for patients with recurrence of symptoms. Patients were also monitored with a hour Holter recording before discharge, and at 3, 6, and 12 months postenrollment. In addition, patients were called by telephone on a monthly basis. All patients in the PVI group had a spiral computed tomographic scan after 3 months. This was repeated at 6 and 12 months, if there was evidence of any degree of pulmonary venous narrowing. All continuous variables are expressed as mean SD and were compared using Student t test. Differences among groups of continuous variables were determined by analysis of variance. SPSS version For the 2-month period after enrollment, AF recurrence and hospitalizations in both treatment groups were reported separately. This 2-month period was used to account for AF recurrences and hospitalizations that occurred during antiarrhythmic drug titration and to account for the fact that AF recurrence early after PVI may be transient and does not necessarily imply failure of PVI 19 ; therefore, these data are reported separately to minimize bias against the antiarrhythmic drug group of the study. However, for descriptive purposes, we also present a Kaplan-Meier curve of AF-free survival that includes all events and data during these 2 months. From December 31, , to July 1, , 70 patients were enrolled. Baseline characteristics of the study population are shown in Table 1 and Figure 1. The mean duration of AF symptoms and left ventricular ejection fraction in both groups were comparable. During the initial 2 months of follow-up, 20 patients in the antiarrhythmic drug group had recurrence of AF, which resulted in 26 hospitalizations for direct current cardioversion and medication adjustment. There were no hospitalizations in the PVI group during this period. No thromboembolic events occurred in either group. Three patients 2 in the antiarrhythmic drug group and 1 in the PVI group did not present for follow-up and were excluded from the primary analysis. These 3 patients were still alive based on vital statistics information available at the time of preparation of this article. There were no repeat ablation procedures throughout the 1-year period. The 1-year follow-up results are shown in Table 2 and Table 3. Three patients received the initial antiarrhythmic drugs only; in 6 patients, the dose of the initial antiarrhythmic drugs was increased; and in the remaining 16, the initial drug was changed to an alternative drug. Of the 27 patients who received flecainide, 20 experienced recurrence of symptomatic AF. Of those patients, the dosage was increased in 5 patients and changed to a second antiarrhythmic drug in 15 patients. Two of the 8 patients who received sotalol as the initial antiarrhythmic drug experienced recurrence of AF; amiodarone was then initiated for 1 patient and the dose was increased in the second patient. Figure 2 is a Kaplan-Meier curve presenting AF recurrences in both groups. At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in quality of life in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey Table 4. There were no thromboembolic events, defined as transient ischemic events, stroke, deep vein thrombosis, or pulmonary embolism, in either treatment group. Bleeding rates were similar in both groups. Incidence of documented bradycardia was higher in the antiarrhythmic drug group 3 \[8. After the 1-year follow-up dictated by the study protocol, 4 patients who had recurrence of AF in the PVI group underwent a second procedure. Three of these patients have remained AF free and are not taking antiarrhythmic drugs and 1 patient is in sinus rhythm with antiarrhythmic drug therapy. In the antiarrhythmic drug group, 3 of the patients with recurrence developed chronic AF. Of these patients, 15 are AF free and are not taking antiarrhythmic drugs and 3 are in sinus rhythm with antiarrhythmic drug therapy. One-year follow-up data were complete for all study participants except for the 3 patients who did not return for follow-up. To assess the possible effect of these missing data, we performed a sensitivity analysis assuming a worst-case scenario in which 1 patient in the PVI group was assumed to have AF recurrence and 2 patients in the antiarrhythmic drug group were assumed to have remained AF free. Under a similar worst-case scenario for hospitalization, there is little difference from the primary analysis. This is the first randomized study to our knowledge demonstrating that a strategy of using first-line PVI for symptomatic AF is associated with improved clinical outcomes compared with initial antiarrhythmic drug therapy. Pulmonary vein isolation was associated with less AF recurrence, improved quality of life, and a lower hospitalization rate during follow-up after the initial 2 months of follow-up. During the initial 2 months of follow-up, there were more recurrences in AF in both groups compared with the results reported at 1 year. However, events were higher in the antiarrhythmic drug group in this period. The initial 2 month period was used to account for AF recurrences and hospitalizations that occur during antiarrhythmic drug titration and to account for the fact that AF recurrence early after PVI may be transient and does not necessarily imply failure of PVI. Recent randomized trials 2 , 8 have shown that a strategy of rate control is comparable with a strategy of rhythm control using antiarrhythmic drugs in treating many patients with AF. We did not include a rate-control group because our study was initiated at a time when the results of these trials were unknown. Even so, the degree to which the results of these trials can be applied to our patient population is unclear. Our study population mainly consisted of younger patients with highly symptomatic AF. This population was underrepresented in recent trials, 2 , 8 which included mostly elderly patients with recurrent persistent AF. Elderly patients tend to be less symptomatic than younger patients with paroxysmal AF 20 ; therefore, a strategy limited to rate control in younger patients with symptomatic AF may not be as effective in controlling symptoms. In addition, the benefits of restoring sinus rhythm may be greater in younger patients because doing so may prevent progressive atrial remodeling that leads to chronic AF. The results of the rate-control vs rhythm-control trials might lead to the conclusion that sinus-rhythm restoration is of comparable efficacy with allowing patients to remain in AF with a controlled ventricular rate. Such a conclusion is unwarranted. These studies only showed that a strategy of rhythm control using antiarrhythmic drugs was comparable with a strategy of rate control. A limitation of all these trials is that the rhythm-control strategy was not efficacious. This suggests that the neutral results in the rate-control vs rhythm-control trials might be explained by the fact that the benefits of antiarrhythmic drugs in restoring sinus rhythm were negated by offsetting detrimental effects of antiarrhythmic drug therapy. In theory, a therapy that restores and maintains sinus rhythm while avoiding the deleterious effects of antiarrhythmic drugs would improve survival. Pulmonary vein isolation may be such a therapy. In a recent observational study involving a relatively large number of patients, Pappone et al 24 reported that AF ablation was associated with significantly lower mortality and adverse events compared with drug therapy. In current clinical practice, ablation therapy for AF is reserved for patients with symptoms who have failed multiple antiarrhythmic drug regimens. The primary concern in offering an ablation procedure to treat AF as first-line therapy is that complications from the procedure can occur. These complications include femoral pseudoaneurysm, arteriovenous fistula, pneumothorax, hemothorax, transient ischemic attack, and cardiac tamponade. The most serious complications resulting in permanent disability were uncommon death in 0. Significant pulmonary vein stenosis was reported in 1. Contrasting the risks of PVI are the risks associated with antiarrhythmic drug therapy, which may not be trivial. Our study had several limitations, which included a pilot study with a small number of relatively young patients and the ablation procedures performed at highly specialized centers. The sample size and 1-year follow-up period were not large enough to assess the effects of therapy on important but infrequent outcomes, such as stroke. The long-term cure rate for the PVI procedure is unknown. Quality of life was only assessed at baseline and 6-month follow-up. Although many patients were receiving atrioventricular nodal blocking agents, there was no rate-control group. Because of the potential for end-organ toxicity, the use of amiodarone was discouraged and used infrequently. However, amiodarone may be slightly more effective at maintaining sinus rhythm than other antiarrhythmic drugs. Also, techniques for performing AF ablation continue to change as knowledge, experience, and technology advance. Additionally, cost-effectiveness was not addressed in our study. In future studies, the initial 2-month follow-up period would most likely be taken into account when studying cost-effectiveness. Based on the results of our study, we conclude that PVI is a feasible first-line approach for the treatment of selected patients with symptomatic AF. To further assess whether the benefits of AF ablation outweigh the inherent risks of an invasive procedure requires a multicenter randomized trial with a larger number of centers and patients, and longer follow-up. Until such a study is performed, PVI should not be considered standard of care as first-line therapy for AF. Nevertheless, the results of our study suggest that ablation to cure AF may become the treatment of first choice in appropriately selected patients with AF. Author Contributions: Dr Natale had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Role of the Sponsor: Acuson did not participate in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. Figure 1. Figure 2. PVI indicates pulmonary vein isolation. Table 1. Table 2. Table 3. Table 4. Eur Heart J. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. Atrioventricular nodal modification and atrioventricular junctional ablation for control of ventricular rate in atrial fibrillation. J Cardiovasc Electrophysiol. Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium. Am J Cardiol. Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications. Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Current perspectives on curative catheter ablation of atrial fibrillation. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Pulmonary vein stenosis after catheter ablation of atrial fibrillation: emergence of a new clinical syndrome. Ann Intern Med. Feasibility of pulmonary vein ostia radiofrequency ablation in patients with atrial fibrillation: a multicenter study CACAF pilot study. Pacing Clin Electrophysiol. Bertaglia E. Med Care. Pulmonary vein antrum isolation: intracardiac echocardiography-guided technique. Clinical significance of early recurrences of atrial fibrillation after pulmonary vein isolation. Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Clinical presentation, investigation, and management of pulmonary vein stenosis complicating ablation for atrial fibrillation. Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy. Left atrial-esophageal fistula following radiofrequency catheter ablation of atrial fibrillation. Atrio-esophageal fistula as a complication of percutaneous transcatheter ablation of atrial fibrillation. A fatal complication due to radiofrequency ablation for atrial fibrillation: atrio-esophageal fistula. Ann Thorac Surg. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. Save Preferences. Privacy Policy Terms of Use. This Issue. Citations View Metrics. X Facebook More LinkedIn. Preliminary Communication. Oussama M. Wazni, MD ; Nassir F. Marrouche, MD ; David O. Antiarrhythmic Drug Treatment. Pulmonary Vein Isolation. Statistical Analysis. Study Population. Events During the Initial 2 Months of Follow-up. Follow-up After 2 Months. Quality of Life Assessment. Follow-up After 1 Year. Missing Data. Back to top Article Information. Financial Disclosures: None reported. Access your subscriptions. Access through your institution. Add or change institution. Free access to newly published articles. Purchase access. 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