The beneficial effects of long-term enzyme replacement therapy on cardiac involvement in Japanese Fabry patients.

Fabry disease is a hereditary disorder that occurs due to the reduction or absence of alpha-galactosidase A activity, which leads to cardiac involvement including left ventricular hypertrophy (LVH). Enzyme replacement therapy (ERT) provides better patient outcomes by preventing serious complications. However, there have been very few studies on the long-term effects of ERT on the cardiac manifestations in Japanese Fabry patients. We retrospectively analyzed the data from the medical records of 42 Fabry patients (male, n = 17; female, n = 25) who were followed at Jikei University Hospital, and in whom the long-term effects of ERT could be evaluated (median follow-up period: male, 11 years; female, 8 years). The slope of the left ventricular mass (LVM) increase was 3.02 ±â€¯3.41 g/m2/year in males and 1.69 ±â€¯2.73 g/m2/year in females. In a subgroup analysis, the slopes of males with and without LVH did not differ to a statistically significant extent; however, the slope in female patients without LVH was significantly smaller than that of female patients with LVH. We then compared our data to the natural historical data that have previously been reported. In comparison to the previously reported data, we found a significant reduction in the LVM changes (g/height2.7/year) of patients who received long-term ERT (male, 4.07 ±â€¯1.03 to 1.25 ±â€¯1.39; female, 2.31 ±â€¯0.81 to 0.78 ±â€¯1.23). Long-term ERT effectively prevents LVH in Fabry patients. This effect was also observed in the patients with LVH prior to the initiation of ERT.

The role of successful catheter ablation in patients with paroxysmal atrial fibrillation and prolonged sinus pauses: outcome during a 5-year follow-up.

AIMS: Although patients with paroxysmal atrial fibrillation (AF) and prolonged sinus pauses [tachycardia-bradycardia syndrome (TBS)] are generally treated by permanent pacemaker, catheter ablation has been reported to be a curative therapy for TBS without pacemaker implantation. The purpose of this study was to define the potential role of successful ablation in patients with TBS. METHODS AND RESULTS: Of 280 paroxysmal AF patients undergoing ablation, 37 TBS patients with both AF and symptomatic sinus pauses (age: 62 ± 8 years; mean maximum pauses: 6 ± 2 s) were analysed. During the 5.8 ± 1.2 years (range: 5-8.7 years) follow-up, both tachyarrhythmia and bradycardia were eliminated by a single procedure in 19 of 37 (51%) patients. Repeat procedures were performed in 14 of 18 patients with tachyarrhythmia recurrence (second: 12 and third: 2 patients). During the repeat procedure, 79% (45 of 57) of previously isolated pulmonary veins (PVs) were reconnected to the left atrium. Pulmonary vein tachycardia initiating the AF was found in 46% (17 of 37) and 43% (6 of 14) of patients during the initial and second procedure, respectively. Finally, 32 (86%) patients remained free from AF after the last procedure. Three patients (8%) required pacemaker implantation, one for the gradual progression of sinus dysfunction during a period of 6.5 years and the others for recurrence of TBS 3.5 and 5.5 years after ablation, respectively. CONCLUSION: Catheter ablation can eliminate both AF and prolonged sinus pauses in the majority of TBS patients. Nevertheless, such patients should be continuously followed-up, because gradual progression of sinus node dysfunction can occur after a long period of time.

Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

Improvement of atrioventricular conduction following catheter ablation of atrioventricular nodal reentry tachycardia in a patient with a prolonged PR interval.

We herein present the case of a 60-year-old male with narrow QRS tachycardia who had a remarkable PR prolongation during sinus rhythm. The tachycardia was diagnosed as a slow-fast atrioventricular nodal reentry tachycardia. Slow pathway ablation was performed after the confirmation of the presence of an antegrade fast pathway. Following the elimination of the slow pathway, the PR and atrio-His intervals became shortened from 470 and 420 to 170 and 120 ms, respectively. Moreover, the improvement of atrioventricular conduction after the slow pathway ablation lasted for at least 34 months.

Substrate modification by pulmonary vein isolation and left atrial linear ablation in patients with persistent atrial fibrillation: its impact on complex-fractionated atrial electrograms.

UNLABELLED: PV and Linear Ablation for CFAEs. INTRODUCTION: Linear ablations in the left atrium (LA), in addition to pulmonary vein (PV) isolation, have been demonstrated to be an effective ablation strategy in patients with persistent atrial fibrillation (PsAF). This study investigated the impact of LA linear ablation on the complex-fractionated atrial electrograms (CFAEs) of PsAF patients. METHODS AND RESULTS: A total of 40 consecutive PsAF patients (age: 54 ± 10 years, 39 males) who underwent catheter ablation were enrolled in this study. Linear ablation of both roofline between the right and left superior PVs and the mitral isthmus line joining from the mitral annulus to the left inferior PV were performed following PV isolation during AF. High-density automated CFAE mapping was performed using the NAVX, and maps were obtained 3 times during the procedure (prior to ablation, after PV isolation, and after linear ablations) and were compared. PsAF was terminated by ablation in 13 of 40 patients. The mean total LA surface area and baseline CFAEs area were 120.8 ± 23.6 and 88.0 ± 23.5 cm(2) (74.2%), respectively. After PV isolation and linear ablations in the LA, the area of CFAEs area was reduced to 71.6 ± 22.6 cm(2) (58.7%) (P < 0.001) and 44.9 ± 23.0 cm(2) (39.2%) (P < 0.001), respectively. The LA linear ablations resulted in a significant reduction of the CFAEs area percentage in the region remote from ablation sites (from 56.3 ± 20.6 cm(2) (59.6%) to 40.4 ± 16.5 cm(2) (42.9%), P < 0.0001). CONCLUSION: Both PV isolation and LA linear ablations diminished the CFAEs in PsAF patients, suggesting substrate modification by PV and linear ablations. (J Cardiovasc Electrophysiol, Vol. 23, pp. 962-970, September 2012).

Impact of body mass index on clinical outcome in patients hospitalized with congestive heart failure.

BACKGROUND: Obesity has recently been shown to have a favorable effect on the prognosis of patients with congestive heart failure (CHF), but only a few such studies are available in Japan. The purpose of the present study was to investigate whether the obesity paradox is still present after adjusting for CHF characteristics. METHODS AND RESULTS: A total of 219 patients hospitalized with CHF were reviewed, and the impact of body mass index (BMI) on prognosis was examined. Patients were divided into 4 groups according to BMI quartiles. The endpoint was defined as all-cause death or unplanned CHF hospitalization. According to univariate analysis, a higher BMI was associated with better outcomes. High-BMI patients were younger, likely to be male, and had a higher prevalence of hypertension and diabetes. The plasma B-type natriuretic peptide (BNP) levels and blood urea nitrogen (BUN) levels were lower, while the serum hemoglobin and sodium levels were higher in high-BMI patients. The prevalence of atrial fibrillation was lower in high-BMI patients. Predictors for all-cause death or CHF hospitalization based on univariate analysis were age, prior CHF hospitalization, estimated glomerular filtration rate, plasma BNP levels, BUN levels, and serum hemoglobin and sodium levels. According to multivariate analysis, a high BMI was still associated with better outcomes. CONCLUSIONS: High BMI was associated with better clinical outcomes in Japanese CHF patients.

Identification of a conduction gap of the mitral isthmus by using a novel high-density mapping catheter.

Peri-mitral atrial flutter, which is a type of macroreentrant atrial tachycardia circulating around the mitral annulus, was terminated with the guidance of the high-density mapping catheter. A 72-year-old woman with atrial fibrillation and atrial tachycardia presented with symptoms of congestive heart failure. The recurrent peri-mitral atrial flutter following the initial catheter ablation for atrial tachycardia and atrial fibrillation was terminated by radiofrequency application on the gap that was identified using a novel high-density mapping catheter.

Real-time dominant frequency analysis of the pulmonary vein in patients with paroxysmal atrial fibrillation.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) can be treated with pulmonary vein isolation (PVI). A spectral analysis can identify sites of high-frequency activity during atrial fibrillation (AF). We investigated the role of the PVs on AF perpetuation by dominant frequency (DF) analysis. METHODS: Thirty-one consecutive patients with PAF who underwent PVI were included in the prospective study. DF was calculated in each of the PVs, 16, five, and five sites in the left atrium, the coronary sinus, and the right atrium, respectively. In patients presenting sinus rhythm at the baseline, AF was induced by pacing. The PVs were then divided into two groups; PVs demonstrated the highest DF (HDF-PV) and others. RESULTS: One patient was excluded from the analysis because sustained AF could not be induced. AF was terminated in 43.3% (13/30) of patients during ablation. Of 92 PVs isolated during AF, 30 and 62 PVs were classified into the HDF-PV and others, respectively. PAF was more frequently terminated by the HDF-PV isolation compared to the others (33.3% [10/30] vs 4.8% [3/62], P = 0.0004). Interestingly, nine of the 30 HDF-PVs showing the highest DF among all 30 regions, including extra PVs, led to AF termination in 88.9% (eight out of nine) of cases. Moreover, the HDF-PVs isolation resulted in a greater AF cycle length prolongation than the other PVs isolation (12.1±5.0 vs 2.7±7.6 ms, P = 0.007). CONCLUSION: Termination of PAF was more frequently observed during ablation of the PVs with the highest DF. The PV showing high DF played an important role in the maintenance of PAF.

Adenosine-induced atrial tachycardia and multiple foci initiating atrial fibrillation eliminated by catheter ablation using a non-contact mapping system.

A 47-year-old male with both atrial tachycardia and atrial fibrillation underwent catheter ablation. During the procedure, rapid administration of adenosine triphosphate induced atrial tachycardia. A non-contact mapping system revealed a focal atrial tachycardia originating from the lateral right atrium, which was successfully ablated. Following the ablation of tachycardia, atrial fibrillation was induced by the injection of adenosine along with multiple extra pulmonary vein foci, which were eliminated by the application of radiofrequency under the guidance of a non-contact mapping system.

Dormant pulmonary vein conduction induced by adenosine in patients with atrial fibrillation who underwent catheter ablation.

BACKGROUND: intravenous administration of adenosine triphosphate (ATP) is used to induce transient pulmonary vein (PV) reconduction (dormant PV conduction) following PV isolation. This study investigated the detailed characteristics of dormant PV conduction in patients with atrial fibrillation (AF) who underwent catheter ablation. METHODS: two hundred sixty consecutive patients (235 men; mean age, 54 ± 10 years) who underwent catheter ablation of their AF were included in this study. ATP was injected following PV isolation to induce dormant PV conduction, which was then eliminated by radiofrequency application. RESULTS: dormant PV conduction was induced by ATP in 60.4% (157/260) of the patients and in 25.3% (258/1,021) of the isolated PVs. This transient PV reconduction was more frequently observed in the left superior PV in comparison with other PVs (P < .0001). There was no significant difference in the prevalence of the dormant PV conduction among patients with paroxysmal AF, persistent AF, and long-lasting AF (62%, 66%, and 48%, respectively; P = .13). During the follow-up period, repeat AF ablation was performed in 70 patients with recurrent AF. The dormant PV conduction was less frequently induced in the repeat procedure than in the initial procedure (60.4% vs 31.4%, P < .0001). CONCLUSIONS: dormant PV conduction was evenly induced among AF types. The repeat PV isolation led to the decrease in incidence of the ATP-induced acute transient pharmacological PV reconduction.

Completion of mitral isthmus ablation using a steerable sheath: prospective randomized comparison with a nonsteerable sheath.

BACKGROUND: Although mitral isthmus (MI) ablation in atrial fibrillation (AF) patients has been shown to be an effective ablative strategy, the establishment of the bidirectional conduction block of the MI is technically challenging. We investigated the usefulness of a steerable sheath for MI ablation in patients with persistent AF and its impact on the clinical outcome of persistent AF ablation. METHODS: A total of 80 consecutive patients undergoing MI ablation were randomized to 1 of the following 2 groups: group S (using a steerable long sheath) or group NS (using a nonsteerable long sheath). MI ablation was performed by using an open-irrigated ablation catheter with the guidance of a 3-dimensional mapping system. The endpoint of the MI ablation was the achievement of a bidirectional block. RESULTS: Bidirectional block through the MI was achieved in 87.5% (70/80) of patients with 14.0 ± 6.7 minutes of radiofrequency application. The bidirectional block was more frequently achieved in patients in group S compared to group NS (97.5% (39/40) vs 77.5% (31/40), P = 0.02). Additionally, epicardial ablation within the coronary sinus was less frequently required in group S compared to group NS (12.5% (5/40) vs 72.5% (29/40), P < 0.0001). Atrial tachycardia after the procedure more frequently occurred in the patients in whom MI block had not been achieved during the initial procedure (40.0% (4/10) vs 10.0% (7/70), P = 0.04). CONCLUSIONS: The MI block could be achieved in the majority of patients by using a steerable sheath. An incomplete MI block increased the risk of AT following persistent AF ablation.

Different strategies for performing pulmonary vein isolation in patients with pulmonary vein rhythm.

Pulmonary vein (PV) isolation was performed in atrial fibrillation (AF) patients whose cardiac rhythm was dominated by the ectopic beats originating from the PV. We herein report two cases with dominant PV ectopic rhythm that underwent catheter ablation for the treatment of paroxysmal AF. In one case, a permanent pacemaker implantation was required to treat a symptomatic long sinus pause after the isolation of all four PVs, while no AF was documented during the 5-year period after ablation. However, the isolation of all four PVs except for a PV with a dominant ectopic rhythm was performed in the other case. The latter case was free from both AF and symptomatic bradycardia following the procedure without the implantation of a pacemaker. Selective PV isolation therefore appears to be an effective therapy to both achieve the successful treatment of AF and to prevent the manifestation of sick sinus syndrome.

Comparison of the clinical outcome after pulmonary vein isolation based on the appearance of adenosine-induced dormant pulmonary vein conduction.

BACKGROUND: The elimination of transient pulmonary vein (PV) reconduction (dormant PV conduction) revealed by adenosine in addition to PV isolation reduced the atrial fibrillation (AF) recurrence after catheter ablation. The dormant PV conduction is induced in approximately half of the AF patients that undergo PV isolation. The present study compared the clinical outcome of AF ablation in patients whose dormant PV conduction was eliminated by additional radiofrequency applications with the outcome in patients without dormant conduction. METHODS: A total of 233 consecutive patients (206 male, 54.2 +/- 10.1 years) that underwent AF ablation were included in the present study. Dormant PV conduction was induced by the administration of adenosine triphosphate after PV isolation and was eliminated by supplemental radiofrequency application. All patients were followed up for >12 months (mean 903 days) after the first ablation. RESULTS: Following PV isolation, dormant PV conduction was induced in 139 (59.7%) of 233 patients and was successfully eliminated in 98% (223/228) of those in the first ablation procedure. After the first procedure, 63.9% (149/233) of patients were free from AF recurrence events. The success rates of a single or final AF ablation in patients with the appearance of the dormant PV conduction were similar to those of patients without dormant conduction (P = .69 and P = .69, respectively). CONCLUSIONS: Dormant PV conduction was induced in over half of the patients with AF. After the elimination of adenosine triphosphate-induced reconnection, the clinical outcome of patients with the dormant PV conduction was equivalent to that of patients without conduction.

Prospective randomized comparison of a steerable versus a non-steerable sheath for typical atrial flutter ablation.

AIMS: Although cavotricuspid isthmus (CTI) ablation can cure typical atrial flutter (AFL), it might be difficult to achieve a bidirectional conduction block in the isthmus in some patients. We investigated the usefulness of a steerable sheath for CTI ablation in patients with typical AFL or atrial fibrillation. METHODS AND RESULTS: A total of 40 consecutive patients (36 males; mean age 55.2 +/- 10.0 years) undergoing CTI ablation were randomized to one of the following two groups: group S (using a steerable long sheath) or group NS (using a non-steerable long sheath). Ablation was performed using an 8 mm tip catheter. The anatomy of the CTI was evaluated by a dual-source computed tomography scan prior to the procedure. The procedural endpoint was the achievement of a bidirectional isthmus conduction block. Bidirectional block in the CTI was achieved in all patients with 485.3 +/- 416.4 s of radiofrequency (RF) application. The CTI anatomy, including the length, depth, and morphology, was similar between the two groups. The duration and total amount of RF energy delivery were significantly shorter and smaller in group S than in group NS (310 +/- 193 vs. 661 +/- 504 s, P = 0.006, and 12,197 +/- 7306 vs. 26,906 +/- 21,238 J, P = 0.006, respectively). CONCLUSION: The use of a steerable sheath reduced the time and amount of energy needed to achieve a bidirectional conduction block in the CTI. For patients in whom the establishment of a conduction block is difficult, a steerable sheath should be considered as a therapeutic option for typical AFL ablation.

Recruitment of immune cells across atrial endocardium in human atrial fibrillation.

BACKGROUND: Although clinical studies have suggested a link between inflammation markers and atrial fibrillation (AF), it is still unclear whether local immunologic responses actually exist in human atria during AF. METHODS AND RESULTS: To address this point, human left appendages were obtained from 16 patients who underwent cardiac surgery (5 with sinus rhythm (SR) and 11 with AF) and subjected to immunohistochemical analysis. In all the AF specimens, adhesion and migration of CD45-reactive cells were consistently observed predominantly in the atrial endo- and subendomyocardium and more prominently than in SR. Most of them were immunologically active CD68-positive macrophages, whereas CD3-positive T cells infiltrated to a lesser extent. Scavenger-receptor A staining revealed maturation of macrophages not in the endocardium but in the midmyocardium, a gradient from endo- to midmyocardium. In the endocardium, along with adhesion molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1), a chemotactic protein-1, which facilitates the recruitment, was more abundantly expressed in AF than in SR. Cytokines including transforming growth factor-beta and interleukin-6 were frequently expressed by these macrophages. CONCLUSIONS: These observations collectively imply active adhesion and recruitment of macrophages across the endocardium in human fibrillating atria, thereby supporting the concept of local immunologic inflammatory responses around the atrial endocardium of AF.

Impact of pulmonary vein isolation on the autonomic modulation in patients with paroxysmal atrial fibrillation and prolonged sinus pauses.

AIMS: The efficacy of catheter-based pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (AF) and prolonged sinus pauses [bradycardia-tachycardia syndrome (BTS)] has been already described. However, the effects of PVI on autonomic modulation in BTS patients remain to be determined. We, therefore, examined the alteration in the autonomic modulation through the PVI procedure by using a heart rate variability (HRV) analysis of 24 h ambulatory monitoring. METHODS AND RESULTS: This study consisted of 26 symptomatic paroxysmal AF patients either with prolonged sinus pauses on termination of AF (>3.0 s, BTS group, n = 11) or without any evidence of sinus node dysfunction (control group, matched for sex and age, n = 15) who underwent PVI. All 11 BTS patients became free from both AF and prolonged sinus pauses without pacemaker implantation (23 +/- 14 months of observation). The mean heart rate significantly increased in the control group (P < 0.05), but not in the BTS group after the PVI procedure, although the HRV parameters of root-mean-square successive differences in the adjacent NN intervals, standard deviation of the NN intervals, and high frequency did significantly decrease in both groups (P < 0.05). CONCLUSION: Although the parasympathetic modulation was significantly attenuated after the PVI procedure, the mean heart rate did not increase in the BTS patients, probably due to the pre-existing sinus node dysfunction.

Hypoxemia in inferior pulmonary veins in supine position is dependent on obesity.

RATIONALE: Although arterial oxygen concentration decreases in obese subjects, the mechanism for this remains to be determined. OBJECTIVES: The blood gas level in each pulmonary vein (PV) was measured in supine subjects with diverse body mass index (BMI) values, to determine whether there was a regional insufficiency in gas exchange depending on the subject's BMI. METHODS: Forty subjects with normal cardiopulmonary function who underwent a catheter ablation for atrial fibrillation were included. Before delivering any radiofrequency energy application, blood samples were obtained from each of the four PVs during physiologic breathing in a supine position to measure the PO2 and PCO2 values. Spirometry and ventilation/perfusion lung scintigraphy were also performed. MEASUREMENTS AND MAIN RESULTS: The PO2 value was significantly higher in superior veins than inferior veins (91.8 +/- 13.5, 70.8 +/- 16.3, 92.2 +/- 11.1, and 73.6 +/- 13.7 mm Hg, in the left superior, left inferior, right superior, and right inferior PV, respectively). There was a significant inverse relationship between the PO2 and PCO2 values. Neither the spirometry nor lung scintigraphy could detect any remarkable findings corresponding to the low PO2 values. Among the various clinical characteristics, only the BMI was significantly associated with the decreased PO2 value in the inferior veins. CONCLUSIONS: Hypoxia in obese subjects in a supine position is thus considered to be primarily caused by insufficient gas exchange in the regions of lung linked to the inferior PVs. The inverse relationship between the BMI and PO2 value in the inferior PVs suggests a possible subclinical manifestation of obesity-related respiratory insufficiency.

The dormant epicardial reconnection of pulmonary vein: an unusual cause of recurrent atrial fibrillation after pulmonary vein isolation.

The case of a 65-year-old man with recurrent atrial fibrillation after undergoing segmental pulmonary vein isolation caused by the reconnection of previously isolated pulmonary veins is herein reported. Interestingly, frequent ectopic firings in the left superior pulmonary vein conducted to the left atrium, not through its ostium but through the supposed epicardial pathway at the region of the Marshall ligament, which had been absent during the first treatment session. The reisolation of the left superior pulmonary vein by radiofrequency application in the left atrial appendage thus successfully eliminated the occurrence of atrial fibrillation.

Reduction of AF recurrence after pulmonary vein isolation by eliminating ATP-induced transient venous re-conduction.

BACKGROUND: Recent evidence has suggested that the transient re-conduction of the isolated pulmonary vein (PV) induced by the intravenous injection of adenosine (dormant PV conduction) might predict the incidence of subsequent venous reconnection after the procedure, which is the main cause of the atrial fibrillation (AF) recurrence after PV isolation (PVI). We tested the hypothesis that the elimination of these dormant PV conductions by additional radiofrequency (RF) applications can improve the efficacy of the PVI. METHODS AND RESULTS: One hundred forty-eight patients (124 males; mean age 53 +/- 9 years) with drug-refractory AF underwent the PVI procedure. The standard PVI was performed in 94 patients (Group A), whereas the elimination of adenosine triphosphate (ATP)-induced dormant conduction using additional RF energy was performed in addition to the standard PVI in other 54 patients (Group B). Dormant conduction was observed in 56% of the patients (30/54) in Group B and 95% of these transient re-conductions were successfully eliminated by additional RF applications (mean: 1.5 +/- 1.0 times). During the mean follow-up period of 20 months, recurrences of AF after the procedures were observed significantly less frequently in Group B (20%) than in Group A (40%) (P < 0.05). CONCLUSION: The use of additional RF applications to eliminate transient PV reconnection induced by ATP injection led to a reduction of AF recurrence after PVI, most likely due to the minimization of the subsequent PV reconnection.