Fate of Mitral Regurgitation After Transcatheter Closure of Atrial Septal Defect in Adults Yoichi Takaya, MDa, Yasufumi Kijima, MDa, Teiji Akagi, MDb,*, Koji Nakagawa, MDa, Hiroki Oe, MDa, Manabu Taniguchi, MDa, Shunji Sano, MDc, and Hiroshi Ito, MDa Although the volume overload of pulmonary circulation improves after atrial septal defect (ASD) closure, the increasing left ventricular preload may contribute to mitral regurgitation (MR) deterioration. We aimed to evaluate the impact of MR after transcatheter ASD closure on clinical outcomes in adults. A total of 288 consecutive patients who underwent transcatheter ASD closure were enrolled. Changes in MR were assessed at 1 month after the procedure. The end point was defined as cardiovascular events. After the procedure, MR ameliorated in 3 patients and unchanged in 253, whereas MR deteriorated in 32. During a median follow-up of 24 months, patients with MR deterioration had no cardiovascular events, and the event-free survival rate was not different between patients with MR deterioration and those with MR amelioration or no-change (p [ 0.355). Even in patients with MR deterioration, the New York Heart Association functional class improved after the procedure, with no cases of worsening functional class. Multivariate logistic regression analysis showed that MR deterioration was independently related to advanced age and female gender. The degree of enlargement of mitral valve annulus diameter after the procedure was greater in patients with MR deterioration than in those with MR amelioration or no-change, and it was correlated with the degree of MR deterioration. In conclusion, MR deterioration occurs in a minority of adult patients after transcatheter ASD closure; however, it is not linked with adverse outcomes. MR deterioration may be provoked by geometric changes in mitral valve annulus, especially in women with advanced age. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;116:458e462) Transcatheter closure of atrial septal defect (ASD) has been established as an effective treatment for secundumtype ASD.1e6 Although the volume overload of pulmonary circulation improves after transcatheter ASD closure, the increasing left ventricular preload may contribute to mitral regurgitation (MR) because of the elevation of left ventricular filling pressure. The alterations of atrial function, including atrial stiffness because of the device, may be associated with MR. Additionally, the configuration change of the mitral ring or the device itself touching the ring may cause MR. However, limited information is available regarding MR related to ASD closure.7e11 Hence, the effect of MR after ASD closure on clinical outcomes and the potential mechanisms of the changes in MR remain unknown. Therefore, we aimed to evaluate the fate of MR after transcatheter ASD closure in adult patients and its impact on clinical outcomes and to identify factors related to MR deterioration, including cardiac geometry.
a Department of Cardiovascular Medicine, bCardiac Intensive Care Unit, and cDepartment of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan. Manuscript received January 19, 2015; revised manuscript received and accepted April 16, 2015. See page 461 for disclosure information. *Corresponding author: Tel: (þ81) 86-235-7351; fax: (þ81) 86-2357353. E-mail address: [email protected] (T. Akagi).
0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.04.042
Methods We investigated 337 consecutive adult patients (>18 years) who underwent transcatheter ASD closure in our institution from April 2008 to November 2012. Of those patients, 7 who had mitral valve (MV) prolapse and 42 who did not receive transthoracic echocardiography in our institution at 1 month after the procedure were excluded. The remaining 288 patients constituted our study population. All patients gave written informed consent for the procedure. The study was approved by the ethics committee of our institution. Indications for transcatheter ASD closure were a hemodynamically significant left-to-right shunt on cardiac catheterization and echocardiography and/or clinical symptoms of heart failure or paradoxical embolism.3 Exclusion criteria included pulmonary hypertension with pulmonary vascular resistance >8 Wood units and other concomitant congenital heart diseases. Transcatheter ASD closure was performed as described previously,12 using the Amplatzer Septal Occluder (St. Jude Medical, St. Paul, Minnesota). All patients received aspirin 100 mg/day at least 48 hours before the procedure, and this was continued for 6 months. Clopidogrel was administered at a dose of 50 to 75 mg/day for 1 month after the procedure. Other medications, such as diuretics and antihypertension drugs, were continued. Transthoracic echocardiography (iE33; Philips Medical Systems, Andover, Massachusetts, and Atrida; Toshiba Medical Systems, Tokyo, Japan) was scheduled before and at 1, 3, and 6 months after the procedure. The color www.ajconline.org
Congenital Heart Disease/Mitral Regurgitation of Atrial Septal Defect
Doppler jet area of MR and left atrial area at the time of midsystole were measured by the area trace method in the apical 4-chamber view, and the ratio of MR jet area to left atrial area was calculated. The grade of MR was determined by the ratio, where 0% to 10% was none/trivial, 10% to 20% was mild, 20% to 40% was moderate, and >40% was severe.13,14 MV annulus diameter was measured in the apical 4-chamber and 2-chamber views during systole using the frame-by-frame technique. Left and right ventricular diameters were measured in 2-dimensional parasternal longaxis views. Left ventricular ejection fraction was derived using Teichholz’s formula. Early diastolic MV flow velocity and early diastolic septal mitral annular velocity were measured by pulsewave Doppler and tissue Doppler imaging, respectively. The changes in MR were assessed at 1 month after the procedure in this study because the considerable changes in cardiac geometry occurred within 1 month after the procedure,15e17 and the influence of other factors, including medications for MR, was considered to be less at this time. The amelioration or deterioration of MR was defined as the change in at least 1 grade after the procedure. Follow-up information was obtained by medical records, contact with the patient’s physicians, or interview with the patient or, if deceased, with family members. The end point was defined as cardiovascular events, including cardiovascular death, hospitalization because of heart failure or stroke, or new onset of atrial arrhythmias. Patients were followed from the date of the procedure until the date of first documentation of cardiovascular events or the latest of follow-up. The New York Heart Association functional class and plasma B-type natriuretic peptide levels were also assessed before and at the latest follow-up after the procedure. Data are shown as mean SD for continuous variables and as number and percentage for categorical variables. Statistically significant differences were analyzed by the t test and Mann-Whitney U test for continuous variables and the c2 test for categorical variables. Univariate and multivariate logistic regression analyses were performed to identify factors related to MR deterioration after the procedure. Variables for univariate analysis included age, gender, ASD diameter, pulmonary-to-systemic blood flow ratio, pulmonary artery pressure, New York Heart Association functional class, diuretics use, MR grade, early diastolic septal mitral annular velocity, left ventricular end-diastolic diameter, and MV annulus diameter before the procedure. Odds ratios are shown with 95% confidence intervals. The relations between the changes in the ratio of MR jet area to left atrial area after the procedure and the changes in cardiac geometry after the procedure were evaluated by Pearson’s correlation coefficients. The event-free survival rate was estimated by Kaplan-Meier analysis and compared by the log-rank test. Statistical analysis was performed with JMP, version 8.0 (SAS Institute Inc., Cary, North Carolina), and significance was defined as a value of p
a Department of Cardiovascular Medicine, bCardiac Intensive Care Unit, and cDepartment of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan. Manuscript received January 19, 2015; revised manuscript received and accepted April 16, 2015. See page 461 for disclosure information. *Corresponding author: Tel: (þ81) 86-235-7351; fax: (þ81) 86-2357353. E-mail address: [email protected] (T. Akagi).
0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.04.042
Methods We investigated 337 consecutive adult patients (>18 years) who underwent transcatheter ASD closure in our institution from April 2008 to November 2012. Of those patients, 7 who had mitral valve (MV) prolapse and 42 who did not receive transthoracic echocardiography in our institution at 1 month after the procedure were excluded. The remaining 288 patients constituted our study population. All patients gave written informed consent for the procedure. The study was approved by the ethics committee of our institution. Indications for transcatheter ASD closure were a hemodynamically significant left-to-right shunt on cardiac catheterization and echocardiography and/or clinical symptoms of heart failure or paradoxical embolism.3 Exclusion criteria included pulmonary hypertension with pulmonary vascular resistance >8 Wood units and other concomitant congenital heart diseases. Transcatheter ASD closure was performed as described previously,12 using the Amplatzer Septal Occluder (St. Jude Medical, St. Paul, Minnesota). All patients received aspirin 100 mg/day at least 48 hours before the procedure, and this was continued for 6 months. Clopidogrel was administered at a dose of 50 to 75 mg/day for 1 month after the procedure. Other medications, such as diuretics and antihypertension drugs, were continued. Transthoracic echocardiography (iE33; Philips Medical Systems, Andover, Massachusetts, and Atrida; Toshiba Medical Systems, Tokyo, Japan) was scheduled before and at 1, 3, and 6 months after the procedure. The color www.ajconline.org
Congenital Heart Disease/Mitral Regurgitation of Atrial Septal Defect
Doppler jet area of MR and left atrial area at the time of midsystole were measured by the area trace method in the apical 4-chamber view, and the ratio of MR jet area to left atrial area was calculated. The grade of MR was determined by the ratio, where 0% to 10% was none/trivial, 10% to 20% was mild, 20% to 40% was moderate, and >40% was severe.13,14 MV annulus diameter was measured in the apical 4-chamber and 2-chamber views during systole using the frame-by-frame technique. Left and right ventricular diameters were measured in 2-dimensional parasternal longaxis views. Left ventricular ejection fraction was derived using Teichholz’s formula. Early diastolic MV flow velocity and early diastolic septal mitral annular velocity were measured by pulsewave Doppler and tissue Doppler imaging, respectively. The changes in MR were assessed at 1 month after the procedure in this study because the considerable changes in cardiac geometry occurred within 1 month after the procedure,15e17 and the influence of other factors, including medications for MR, was considered to be less at this time. The amelioration or deterioration of MR was defined as the change in at least 1 grade after the procedure. Follow-up information was obtained by medical records, contact with the patient’s physicians, or interview with the patient or, if deceased, with family members. The end point was defined as cardiovascular events, including cardiovascular death, hospitalization because of heart failure or stroke, or new onset of atrial arrhythmias. Patients were followed from the date of the procedure until the date of first documentation of cardiovascular events or the latest of follow-up. The New York Heart Association functional class and plasma B-type natriuretic peptide levels were also assessed before and at the latest follow-up after the procedure. Data are shown as mean SD for continuous variables and as number and percentage for categorical variables. Statistically significant differences were analyzed by the t test and Mann-Whitney U test for continuous variables and the c2 test for categorical variables. Univariate and multivariate logistic regression analyses were performed to identify factors related to MR deterioration after the procedure. Variables for univariate analysis included age, gender, ASD diameter, pulmonary-to-systemic blood flow ratio, pulmonary artery pressure, New York Heart Association functional class, diuretics use, MR grade, early diastolic septal mitral annular velocity, left ventricular end-diastolic diameter, and MV annulus diameter before the procedure. Odds ratios are shown with 95% confidence intervals. The relations between the changes in the ratio of MR jet area to left atrial area after the procedure and the changes in cardiac geometry after the procedure were evaluated by Pearson’s correlation coefficients. The event-free survival rate was estimated by Kaplan-Meier analysis and compared by the log-rank test. Statistical analysis was performed with JMP, version 8.0 (SAS Institute Inc., Cary, North Carolina), and significance was defined as a value of p
