Background: Previous studies have shown that the highest dominant frequency (DF) is located in the left atrium (LA) during atrial fibrillation (AF) in pacing‐induced AF. However, there have been few studies on the mechanisms of the increased DF of AF during acute atrial dilatation. The purpose of this study was to investigate the mechanisms of the increased maximal DF (max DF) in pacing‐induced AF during acute atrial dilatation. Methods: In eight Langendorff‐perfused canine hearts (26 ± 2 kg), noncontact balloon catheters were placed into the right atrium (RA) and LA, respectively. AF was induced by extrastimulation pre‐ and postdilatation in the atrium (0 and 15 cm H2O, respectively). Fast Fourier transformation analysis was performed to analyze the max DF and harmonic index (HI) from the bi‐atrial unipolar virtual electrograms during AF. The fibrillation cycle lengths were obtained from different atrial sites. The number of wavefronts was analyzed during AF. The frequency of regional splitting was defined as the number of wavefront splits per second in different atrial regions during AF. The percentage of the low‐voltage zones (<0.5 mV) was defined as the ratio of the area of the low‐voltage zones to the total atrial surface area. Results: The DF was measured during AF. The shortest fibrillation cycle length was located in the LA posterior wall and became shorter during acute atrial dilatation. The max DF was located in the LA posterior wall and increased during acute atrial dilatation (7.1 ± 0.8 vs 8.8 ± 2.1, P = 0.02). The max DF of the LA correlated with the wavefront number (r = 0.797, P < 0.001 predilatation; r = 0.860, P < 0.001 postdilatation). The splitting of wavefronts facilitated the formation of new wavefronts. During acute atrial dilatation, the frequency of regional splitting was closely correlated with the percentage of the low‐voltage zones (r = 0.876, P < 0.001). Furthermore, the LA posterior wall had a higher percentage of the low‐voltage zones than the other sites. Conclusion: In acute atrial dilatation, the percentage of the low‐voltage zones increased, especially in the LA posterior wall, which correlated with the regional splitting of the AF wavefronts. The increase in the splitting facilitated the formation of new wavefronts and resulted in a higher max DF during acute atrial dilatation.

OBJECTIVES:This study was aimed at evaluating the efficacy of non-contact mapping and ablation of non-incisional atypical right atrial (RA) flutters. BACKGROUND:The majority of atypical RA flutters were reported in patients after surgical incision of the RA. METHODS:The study group consisted of 15 patients (61 +/- 13 years, 8 males) with atypical atrial flutter (AFL). The RA activation during AFL was delineated using a non-contact mapping system (EnSite 3000 with Precision Software, Endocardial Solutions, St. Paul, Minnesota). The narrowest part of each reentrant circuit was targeted using radiofrequency energy. RESULTS:In all 15 patients, non-contact mapping showed AFLs confined to the RA with RA activation time accounting for 100% of the cycle length (210 +/- 19 ms). During single-loop re-entry in seven patients, the activation wave front circulated around the central obstacle (CO) in the anterolateral wall with conduction through the channel between the CO and the crista terminalis (CT). During figure-of-eight re-entry in eight patients, simultaneous upper and lower loop re-entry through the conduction gap in the CT was found in four patients, and simultaneous upper loop and free-wall single-loop re-entry was observed in four patients. Radiofrequency ablation of the free-wall channel and/or CT gap was effective in eliminating these AFLs in 13 patients. During a follow-up of 16.8 +/- 3.8 months, two patients had recurrence of left AFL, and one had recurrence of atrial fibrillation. CONCLUSIONS:Atypical RA flutters could arise from single-loop or double-loop figure-of-eight re-entry. Radiofrequency ablation of the free-wall channel and/or the CT gap was effective in eliminating these arrhythmias.

Introduction: The aim of this study was to delineate activation patterns around the crista terminalis (CT) using high‐resolution noncontact mapping. Methods and Results: Twenty‐six patients with typical atrial flutter (20 counterclockwise and 6 clockwise) were enrolled in the study. A noncontact mapping system was used to map atrial flutter. There were three activation patterns around the line(s) of block. Type I (n = 6) showed activation around a single complete line of block located in the CT. Type II (n = 17) showed activation around a single incomplete line of block with a conduction gap in the CT. Type III (n = 3) showed activation around double lines of block, one located in the CT and the other located in the sinus venosa region. Simultaneous activation around the tricuspid annulus and through the CT gap could result in double loop reentry (n = 12). After successful ablation of the cavotricuspid isthmus (CTI) in 24 patients, upper loop reentry was still induced in 12 patients with double loop reentry. Subsequent ablation of the CT gap was performed successfully in these 12 patients, and no arrhythmia was inducible thereafter. During the follow‐up period of 8.4 ± 4.1 months, there was no recurrence of atrial flutter in any patient. Conclusion: During typical atrial flutter, the CT might be an incomplete barrier. Simultaneous conduction through the CTI and CT gap could result in double loop reentry. Radiofrequency ablation of the CTI and CT gap was effective in eliminating this arrhythmia. (J Cardiovasc Electrophysiol, Vol. 15, pp. 406‐414, April 2004)

Introduction: High recurrence rate is still a major problem associated with ablation of paroxysmal atrial fibrillation (AF). Most of the recurrences occur within 6 months after ablation. The characteristics of very late recurrent AF (>12 months after ablation) have not been reported. Methods and Results: Two hundred seven patients with drug‐refractory AF underwent successful focal ablation or isolation of AF foci. After the first ablation procedure, Holter monitoring and event recorders were used to evaluate symptomatic recurrent AF. A second ablation procedure was recommended if the antiarrhythmic drugs could not control recurrent AF. During long‐term follow‐up (mean 30 ± 11 months, up to 51 months), 70 patients had recurrent AF, including 13 patients (6%) with very late (>12 months) recurrent AF (group 1) and 57 patients (28%) with late (within 12 months after ablation) recurrent AF(group 2). Group 1 patients had a significantly lower incidence of multiple (≥2) AF foci (23% vs 63%, P = 0.02) than group 2 patients. In addition, the incidence of antiarrhythmic drugs use (38% vs 84%, P = 0.001) to maintain sinus rhythm after the first episode of recurrent AF was significantly lower in group 1 than group 2 patients, and the incidence of a second intervention procedure (8% vs 35%, P = 0.051) tended to be lower in group 1 than group 2 patients. Conclusion: The incidence of very late recurrent AF after ablation of paroxysmal AF is very low, and the clinical outcome of patients with very late recurrent AF is benign. (J Cardiovasc Electrophysiol, Vol. 14, pp. 598‐601, June 2003)

Background-Most of the ectopic beats initiating paroxysmal atrial fibrillation (PAF) originate from the pulmonary vein (PV). However, only limited data are available on PAF originating from the non-PV areas.Methods and Results-Two hundred forty patients with a total of 358 ectopic foci initiating PAF were included. Sixty-eight (28%) patients had AF initiated by ectopic beats (73 foci, 20%) from the non-PV areas, including the left atrial posterior free wall (28, 38.3%), superior vena cava (27, 37.0%), crista terminalis (10, 3.7%), ligament of Marshall (6, 8.2%), coronary sinus ostium (1, 1.4%), and interatrial septum (1, 1.4%). Catheter ablation eliminated AF with acute success rates of 63%, 96%, 100%, 50%, 100%, and 0% in left atrial posterior free wall, superior vena cava, crista terminalis, ligament of Marshall, coronary sinus ostium, and interatrial septum, respectively. During a follow-up period of 22+/-11 months, 43 patients (63.2%) were free of antiarrhythmic drugs without AF recurrence.Conclusions-Ectopic beats initiating PAF can originate from the non-PV areas, and catheter ablation of the non-PV ectopy has a moderate efficacy in treatment of PAF.

OBJECTIVES This study was aimed at delineating the reentrant circuit of right atrial (RA) upper loop re-entry using noncontact three-dimensional mapping.BACKGROUND Various forms of atypical atrial flutter including lower loop re-entry and left atrial flutter have been demonstrated. However, little is known about upper loop re-entry in the RA.METHODS The study population consisted of eight patients (65 12 years, seven men) with atypical atrial flutter. Right atrial activation during atrial flutter was visualized using a noncontact mapping system (EnSite-3000 with Clarity Software, St. Paul, Minnesota) for a three-dimensional reconstruction of the endocardial depolarization. The narrowest part of the re-entrant circuit was targeted using radiofrequency catheter ablation.RESULTS Noncontact mapping showed macro-re-entry confined to the RA free wall with RA activation time accounting for 100% of the cycle length (214 +/- 21 ms) in all eight patients. Two patients had counterclockwise activation, and six patients had clockwise activation around the central obstacle, which was composed of the crista terminalis, the area of functional block, and superior vena cava. The lower turn-around points were located at the conduction gap in the crista terminalis. Radiofrequency linear ablation of the conduction gap in the crista terminalis was performed and eliminated atrial flutter in six patients without recurrence during a follow-up of 3.2 +/- 1.1 months.CONCLUSIONS Atypical atrial flutter could arise from upper loop re-entry in the RA with conduction through the gap in the crista terminalis. Radiofrequency linear ablation of the conduction gap was effective in eliminating this atrial arrhythmia. (C) 2002 by the American College of Cardiology Foundation.

Double Paroxysmal Supraventricular Tachycardias. Introduction: Coexistence of double tachycardias in one patient has been infrequently reported. Furthermore, the mechanisms of transition between double paroxysmal supraventricular tachycardias have not been well studied. Methods and Results: Thirty‐five patients with two paroxysmal supraventricular tachycardias were studied. Group IA consisted of 3 patients with spontaneous transition between AV reciprocating tachycardia (AVRT) and AV nodal reentrant tachycardia (AVNRT). Group IB consisted of 13 patients without spontaneous transition between AVRT and AVNRT. Group IIA consisted of 5 patients with spontaneous transition between AVNRT and atrial tachycardia (AT). Group IIB consisted of 14 patients without spontaneous transition between AVNRT and AT. The absolute values of differences between the two tachycardia cycle lengths were significantly smaller in patients with than in those without transition between the two tachycardias (25 ± 8 msec vs 90 ± 46 msec, P < 0.05, IA vs IB; 21 ± 25 msec vs 99 ± 57 msec, P < 0.01, IIA vs IIB). The cutoff point of 25 msec had 80% positive predictive value for transition between the two tachycardias. Transition between two tachycardias occurred due to a spontaneous premature atrial complex (30%), conduction block at one limb of tachycardia (20%), or tachycardiainduced tachycardia (50%). Absence of transition between two tachycardias might be explained by the absence of a spontaneous premature atrial complex, longer cycle length of the first tachycardia, larger difference between two tachycardia cycle lengths, or induction of each tachycardia under different situations. Conclusion: Double supraventricular tachycardias with similar tachycardia cycle lengths are vulnerable to transition between different tachycardias.

Background The atrial musculature in the cavotricuspid isthmus is a part of posterior inputs to the AV node. In patients with typical atrial flutter, effects of radiofrequency ablation of this isthmus on AV node conduction are still unknown. Methods and Results This study included 16 patients with clinically documented typical atrial flutter. Group 1 had 8 patients without and group 2 had 8 patients with dual AV nodal pathway physiology. Electrical pacing from the interatrial septum and low right atrium was performed to evaluate antegrade AV node function before and after ablation of the cavotricuspid isthmus. In group 1, the AV node conduction properties were similar before and after ablation. In group 2, the AV node Wenckebach cycle length and maximal AH interval during low right atrium (356±58 versus 399±49 ms, P =0.008; 303±57 versus 376±50 ms, P =0.008) and interatrial septum (365±62 versus 393±59 ms, P =0.008; 324±52 versus 390±60 ms, P =0.008) pacing were significantly longer after ablation. Elimination of the slow pathway after ablation was noted in 2 patients, including 1 with AV nodal reentrant echo beats. Conclusions Radiofrequency ablation of the cavotricuspid isthmus was effective in eliminating typical atrial flutter without injury of antegrade fast AV node conduction. The atrial musculature in the cavotricuspid isthmus significantly contributed to the slow AV node conduction.

OBJECTIVES:This study investigated the extent of fractionation of paced right atrial electrograms in patients with and without paroxysmal atrial flutter (AFL) or atrial fibrillation (AF). BACKGROUND:Slow conduction through nonuniform anisotropic atrial muscles, represented by fractionated electrograms, may favor the generation of atrial tachyarrhythmias. METHODS:This study included 10 control patients (Group 1), 8 patients with documented paroxysmal AFL (Group 2) and 10 patients with documented paroxysmal AF (Group 3). Five electrode catheters were placed in the different sites of the right atrium and one catheter was positioned at the coronary sinus ostium. Atrial pacing from one site was done by a constant drive train with an extrastimulus inserted every fourth beat while recording at the other five sites was performed. The delay of each fractionated potential in the high-pass filtered atrial electrogram in response to extrastimulation was determined and used to construct conduction curves of delay versus the S1S2 interval. RESULTS:The mean increase in electrogram duration between a coupling interval of 350 ms and 10 ms above atrial refractoriness was significantly greater in Groups 2 and 3 compared with that in Group 1 (8.5 +/- 2.5 vs. 11.0 +/- 2.7 vs. 5.9 +/- 2.3 ms, respectively, p < 0.001). The mean S1S2 interval at which delay increased suddenly was also longer in Groups 2 and 3 compared with Group 1 (326 +/- 9 vs. 343 +/- 12 vs. 307 +/- 17 ms, respectively, p < 0.001). CONCLUSIONS:Increased delays in the individual potential of the fractionated atrial electrograms may be related to the development of AFL and AF.

Low density lipoprotein (LDL) oxidation and lipid accumulation are thought to enhance the progression of atherosclerosis. Apolipoprotein H (apoH) has been implicated in the development of human atherosclerosis. However, the roles of apoH in the oxidative modification of LDL and cellular accumulation of lipid constituents remained uncharacterized. In this study, the level of plasma apoH was found to be significantly associated with the oxidative susceptibility of LDL in human subjects. Plasma levels of apoH were positively correlated with the lag time but negatively correlated with LDL oxidation rate in conjugated diene formation. By using a J774 A.1 macrophage culture system, we found that apoH could not only inhibit the formation of conjugated diene and thiobarbituric acid-reactive substances, but also reduce the electrophoretic mobility of oxidized LDL. Furthermore, apoH decreased cellular accumulation of cholesterol via a reduction in cholesterol influx and an increase in cholesterol efflux. This is the first demonstration that apoH appears to have "antioxidant"-like effects on LDL oxidation. The results also suggest that apoH can inhibit the translocation of cholesterol from extracellular pools to macrophages, suggesting that apoH may play an important role in the prevention of atherosclerosis.

OBJECTIVES We investigated the electrophysiologic characteristics in the initiation of paroxysmal atrial fibrillation (PAF) from a focal area.BACKGROUND The electrophysiologic characteristics in the initiation of PBF are still not clear.METHODS The study group consisted of 77 patients (M/F = 65/12, age 66 +/- 12 years) with frequent episodes of PAF; we analyzed: 1) 15 cycle lengths of electrical activity before the onset of atrial fibrillation (AF); 2) coupling interval (CI) of the first ectopic beat just before the initiation of AF: and 3) the prematurity; of an ectopic beat (prematurity index [PI] = CI/mean of preceding 15 cycle lengths).RESULTS A total of 111 episodes of sustained AF were identified, Two patterns of AF initiation were observed: group I (59/111, 53%) included the episodes preceded bu cycle length oscillation, and group II (52/111, 47%) included the episodes initiated by a single ectopic beat with preceding cycle. length relatively constant. The PI of group I episodes was significantly greater than that of group II (0.41 +/- 0.12 vs. 0.34 +/- 0.10, p < 0.01). The CI (267 +/- 54 ms vs. 217 +/- 55 ms, p < 0.05), AF1 (194 +/- 36 ms rs. 153 +/- 37 ms, p < 0.05) and PI (0.49 +/- 0.13 ts. 0.37 +/- 0.11, p < 0.01) of the AF episodes from the superior vena cava (SVC) were significantly longer and greater than those of AF episodes from pulmonary veins (PVs).CONCLUSIONS In patients with PAF originating from PVs or the SVC, two major initiating patterns were found. Moreover, the electrophysiologic characteristics in the initiation of AF originating from the SVC were also different from those of AF initiating from the PVs. (J Am Coll Cardiol 2001;37:1658-64! (C) 2001 by the,American College of Cardiology.

BACKGROUND:Regional differences in recovery of tachycardia-induced changes of atrial electrophysiological properties have not been well studied.METHODS AND RESULTS:In the control group (5 dogs), atrial effective refractory period (AERP) and inducibility of atrial fibrillation (AF) were assessed before and every 4 hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8-week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF were assessed before and after complete AVJ ablation with 8-week rapid right atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs), AERP and inducibility of AF were assessed before and after 8-week rapid left atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were obtained from 7 epicardial sites. In the control group, atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change. In the 2 experimental groups, recovery of atrial electrophysiological properties included a progressive recovery of AERP shortening, recovery of AERP maladaptation, and decrease of duration and episodes of reinduced AF. However, recovery of shortening and maladaptation of AERP and inducibility of AF was slower at the LA than at the RA and Bachmann's bundle.CONCLUSIONS:The LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties, and this might play a critical role in initiation of AF.

BACKGROUND Multifocal atrial tachycardia (MAT) is a difficult clinical problem generally associated with acute cardiorespiratory illness. The purpose of this study was to assess the feasibility and clinical usefulness of atrioventricular (AV) junction modification as a nonpharmacologic therapy for medically refractory MAT. METHODS AND RESULTS Thirteen patients with COPD and medically refractory MAT underwent AV junction modification. Complications and outcome of this procedure were monitored. Subjective perceptions of quality of life assessed by a semiquantitative questionnaire and cardiac performance study were obtained before ablation (baseline) and 1 and 6 months after ablation. Radiofrequency energy was applied until the average ventricular rate fell to < 100 beats/min. Ablation procedures controlled the ventricular response in 11 of 13 patients (84%). One patient had unsuccessful modification. Another patient developed delayed complete AV block on the second day after ablation. In these 13 patients, average ventricular rate was reduced from a mean of 145 +/- 11 to 89 +/- 22 beats/min immediately after the ablation (p < 0.01). One patient had recurrent symptomatic MAT at 1 month after ablation; this patient underwent a second procedure without late recurrence. All patients were followed up for at least 6 months (mean, 11 +/- 5 months; range, 6 to 18 months). General quality of life and frequency of significant symptoms improved significantly in patients with successful modification at 1 and 6 months. The left ventricular ejection fraction increased significantly after ablation (44.5 +/- 7.3% at baseline, 49.4 +/- 4. 2% at 1 month, and 50.0 +/- 4.9% at 6 months; all p < 0.05). However, right ventricular ejection fraction remained unchanged (34.7 +/- 6. 2% at baseline, 35.7 +/- 4.4% at 1 month, and 34.3 +/- 4.6% at 6 months; all p > 0.05). The consumption of health-care resources (including frequency of hospital admission and emergency department attendance, antiarrhythmic drug trials) decreased significantly 6 months after AV junction modification. Pulmonary function and theophylline level remained unchanged during follow-up. CONCLUSIONS AV junction modification offers an effective therapy for controlling ventricular rate in medically refractory MAT. This procedure improves the quality of life and left ventricular function in selected patients with symptomatic and medically refractory MAT.

Introduction: Use of endocardial atrial activation sequences from recording catheters in the right atrium, His bundle, and coronary sinus to predict the location of initiating foci of atrial fibrillation (AF) before an atrial transseptal procedure has not been reported. The purpose of the present study was to develop an algorithm using endocardial atrial activation sequences to predict the location of initiating foci of AF before transseptal procedure.Methods and Results: Seventy-five patients (60 men and 15 women, age 68 +/- 12 years) with frequent episodes of paroxysmal AF were referred for radiofrequency ablation. By retrospective analysis, characteristics of the endocardial atrial activation sequences of right atrial, His-bundle, and coronary sinus catheters from the initial 37 patients were correlated with the location of initiating foci of AF, which were confirmed by successful ablation, The endocardial atrial activation sequences of the other 38 patients were evaluated prospectively to predict the location of initiating foci of AF before transseptal procedure using the algorithm derived from the retrospective analysis. Accuracy of the value <0 msec (obtained by subtracting the time interval between high right atrium and His-bundle atrial activation during atrial premature beats from that obtained during sinus rhythm) for discriminating the superior vena cava or upper portion of the crista terminalis from the pulmonary vein (PV) foci was 100%, When the interval between atrial activation of ostial and distal pairs of the coronary sinus catheter of the atrial premature beats was <0 msec, the accuracy for discriminating left PV foci from right PV foci was 92% in the 24 foci from the left PVs and 100% in the 19 foci from the right PVs,Conclusion: Endocardial atrial activation sequences from right atrial, His-bundle, and coronary sinus catheters can accurately predict the location of initiating foci of AF before transseptal procedure. This may facilitate mapping and radiofrequency ablation of paroxysmal AF.

We present a case of primary hyperparathyroidism with hypercalcemia in a patient who had spontaneous attacks of ventricular tachycardia. Right ventricular burst pacing reproducibly induced ventricular tachycardia in the electrophysiological laboratory after intravenous administration of calcium‐gluconate, and verapamil could terminate the tachycardia. After resection of the parathyroid adenoma, the calcium level was restored to normal, and ventricular tachycardia did not occur again during the follow‐up period,

Several atrial pacing modes have been reported to be effective in the prevention of atrial fibrillation (AF); they included biatrial pacing, dual site right atrial pacing, Bachmann's bundle (BB) pacing, and coronary sinus pacing. However, the relative efficacy and electrophysiological mechanisms of these pacing modes in the prevention of AF are not clear. In 15 patients (age 54 ± 14 years) with paroxysmal AF, P wave duration, effective refractory period, and atrial conduction time were determined with six different atrial drive pacings, that were right atrial appendage (RAA), BB, right posterior interatrial septum (RPS), distal coronary sinus (DCS), RAA plus RPS simultaneously (DSA), and RAA plus DCS simultaneously (BiA). All these patients consistently had AF induced with early RAA extrastimulation coupling to RAA drive pacing. No patient had AF induced with RAA extrastimulation coupled to BB, RPS, or DCS drive pacing, but seven and eight patients had AF induced with RAA extrastimulation coupled to DSA and BiA drive pacing, respectively. The P wave duration was longest during RAA pacing, and became shorter during other atrial pacing modes. Analysis of electrophysiological change showed that early RAA extrastimulation coupled to RAA drive pacing caused the longest atrial conduction delay among these atrial pacing modes; BB, RPS, and DCS drive pacing caused a greater reduction of this conduction delay than DSA and BiA drive pacing. In addition, the effective refractory periods of RAA determined with BB, RPS, and DCS drive pacing were similar and longer than that determined with DSA and BiA drive pacing. In patients with paroxysmal AF, this arrhythmia was readily induced with RAA extrastimuli coupled to RAA drive pacing. BB, RPS, and DCS pacing were similar and more effective than DSA and BiA pacing in preventing AF.

BACKGROUND:Irbesartan is a newly developed angiotensin II receptor antagonist. Its antihypertensive efficacy and safety in Taiwanese patients with mild to moderate hypertension remains to be determined.METHODS:This was a multicenter, double-blind, randomized, parallel group study. One hundred and sixteen patients from three centers were enrolled. After a placebo lead-in period of 14 days, 55 patients (24-75 years-of-age) who had a mean seated diastolic blood pressure of 95 to 110 mmHg were randomized to once-daily treatment with irbesartan 150 mg or enalapril 10 mg. Doses were doubled at week 4 if trough seated diastolic blood pressure was 90 mmHg or more. Trough blood pressure was measured at zero, two, four and eight weeks of treatment.RESULTS:Both treatments lowered blood pressure with no significant difference in efficacy between treatment groups. Irbesartan 150 mg to 300 mg provided reductions in trough seated systolic and diastolic blood pressures at week 8 of -16.5 mmHg and -7.2 mmHg, respectively, with 36% of patients having a favorable response. Similarly, enalapril 10 mg to 20 mg reduced systolic and diastolic blood pressure by -10.6 mmHg and -5.0 mmHg, respectively, with a response rate of 43%. Headache, malaise and dizziness were the major adverse reactions observed in both groups. The incidence of drug-related cough was significantly higher with enalapril (18%) than with irbesartan (0%).CONCLUSIONS:Irbesartan 150 mg to 300 mg once daily was as effective in lowering blood pressure as enalapril 10 mg to 20 mg once daily. Both irbesartan and enalapril were well tolerated, while there was a significantly lower incidence of cough with irbesartan compared with enalapril.