1
ORIGINAL ARTICLE Left Ventricular Hemodynamic Changes and Clinical Outcomes after Transcatheter Atrial Septal Defect Closure in Adults Peter Ermis, MD,* Wayne Franklin, MD,* Venkatachalam Mulukutla, MD,* Dhaval Parekh, MD,* and Frank Ing, MD† *Department of Pediatric Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, Tex, USA; † Department of Pediatric Cardiology, Children’s Hospital of Los Angeles, Los Angeles, Calif, USA ABSTRACT
Objectives. The objectives of this study are to assess current management algorithms for left ventricular (LV) hemodynamic and diastolic changes following atrial septal device occlusion in adult patients. Background. Percutaneous closure is now routine for atrial septal defects (ASDs). Previous studies show ventricular size normalization following percutaneous closure. Case reports have discussed the incidence of early LV dysfunction following ASD device placement with some recommending delay of closure or placement of a fenestrated device in patients with elevated LV pressures. Method. All adult patients with an isolated secundum ASD who underwent percutaneous repair were included in this study. In addition to placement of the Amplatzer septal occluder, all patients had a pre and postprocedure transthoracic echocardiography performed measuring myocardial performance index (MPI). Left ventricular end diastolic pressure (LVEDP) was measured before and after balloon occlusion. Results. Nineteen patients (17 female and two male) were included in this study. Average age was 47.2 years (± 12.7 years). All defects were of clinical significance with average Qp : Qs = 2.0 (± 0.6). Balloon occlusion led to a significant (P < .01) increase in LVEDP (pre-LVEDP mean = 7.1 mm Hg, post-LVEDP mean = 15.3 mm Hg). There was no significant change in MPI. ASD device size displayed a modest correlation relative to the change in LVEDP (R = 0.42, P = .09). Conclusions. Percutaneous ASD closure induces an increase in LVEDP. Despite this, all patients tolerated device closure without complication. It appears safe to close ASDs in these patients. Key Words. Adult Congenital Heart Disease; Atrial Septal Defect; Percutaneous Catheter Intervention
Introduction
S
ecundum atrial septal defects (ASDs) account for 7–12% of all congenital heart disease in childhood and up to 22% in the adult population.1–3 While the majority of children are asymptomatic, most adults present with symptoms such as exercise intolerance, dyspnea, or palpitations.4 Closure of ASDs has been shown to result in a significant decrease in symptoms and exercise improvements.3,5 First demonstrated by King and Mills in the 1970s, ASDs are now routinely closed via an intravascular transcatheter approach using a variety of occlusion devices. Since its introduction in the 1990s, the Amplatzer septal occluder (ASO) © 2014 Wiley Periodicals, Inc.
(St. Jude Medical, St. Paul, MN, USA) is now the most commonly used device for these percutaneous interventions. The ASO is one of only two devices approved by the Federal Drug Administration (FDA) for ASD closure.6–9 Previous studies show right and left ventricular (LV) size improvement by echocardiographic assessment within 24 hours following percutaneous closure and normalization of biventricular size within 1 year.1,3,5,10,11 A small number of studies have discussed the incidence of early LV dysfunction following device placement in adults. Also, it is widely accepted that LV diastolic function decreases with age. Several case reports have discussed early ventricular dysfunction following Congenit Heart Dis. 2014;••:••–••
2 device closure in patients with known restrictive LV physiology.1,11–15 Some authors have reported LV conditioning with diuretics (primarily furosemide therapy) or dopamine prior to ASD closure in the patient with a markedly restrictive LV.16,17 Other studies have reported closure with fenestrated occluder devices in these patients.18,19 We hypothesized that an abrupt cessation of left to right atrial level shunting at the time of device closure will lead to an acute increase in LV end diastolic pressures (LVEDP), especially in the elderly patient with decreased LV compliance, left atrial hypertension, and pulmonary edema. We believe that this acute change in hemodynamics will be represented by an increase in signs of volume overload following device placement. No observational studies have reported direct measurements of LV pressure to evaluate acute hemodynamic changes following percutaneous ASD repair. Our study directly measures LVEDP before and after ASD occlusion. Materials and Methods
All adult patients under the care of the Adult Congenital Heart Disease Service with an isolated secundum ASD who underwent percutaneous repair at our institution from November 2006 to November 2010 were prospectively included in this study. All hospital records and catheterization reports were reviewed. All ASDs were closed using standard technique. The catheterization procedures utilized conscious sedation with fentanyl and versed. A right heart catheterization was completed and saturations obtained to calculate Qp : Qs. Afterward, a pigtail catheter was advanced to the LV, and LVEDP was measured. Then, a sizing balloon was used to occlude the defect, and the LVEDP measurements once again were recorded. Using the assistance of intracardiac echocardiography, the ASD was closed. In addition to ASD closure, patients had pre and postprocedure transthoracic echocardiography performed to record mitral inflow and LV outflow tract Doppler measurements. Myocardial performance index (MPI; MPI = isovolemic contraction time + isovolemic relaxation time/ejection time) was measured before and after device implantation via transthoracic echocardiographic Doppler measurements. Institutional review board approval was obtained for this study. Statistical analysis was performed using spss (IBM SPSS Statistics, Chicago, IL, USA). The paired Student t-test was perCongenit Heart Dis. 2014;••:••–••
Ermis et al. formed to determine statistical differences in measurement over time. Linear regression analysis and analysis of variance (ANOVA) were utilized to calculate correlation factors. A P value of less than .05 was considered statistically significant.
Results
Nineteen patients (Table 1) were included in this study. Mean age was 47.2 years (± 12.7) with an average body mass index of 25.8 (± 6.3). Of the 19 patients, six patients had a medical history of hypertension, two patients had hyperlipidemia, one patient had history of stroke, one patient with hypothyroidism, and one patient had a history of coronary artery disease with previous percutaneous coronary intervention to the left anterior descending (Table 1). No additional comorbid medical conditions were present. None of the patients had LV hypertrophy by preoperative transthoracic echocardiogram, calculated by standard measurements. The mean Qp : Qs was 2.0 (± 0.6). The median septal defect size as measured by static balloon sizing under fluoroscopy and intracardiac echocardiography was 22 mm (14–29) and 20 mm (12.5– 28.5), respectively. The median ASO size device implanted was 20 mm (14–30). No fenestrated devices were implanted. Pre- and postocclusion LVEDP measurements were available in all patients while pre- and postocclusion MPI measurements were available in 14 of the 19 patients. The decreased number of MPI data relates to those studies having inadequate echo images obtained to properly make this measurement. The mean LVEDP increased from 7.1 to 15.3 mm Hg after device occlusion, which was statistically significant (P < .01) (Figure 1). The MPI, however, did not display a statistically significant change. A total of five patients had an LVEDP after balloon occlusion that was greater than 20 mm Hg. Three of these patients had a preocclusion LVEDP of greater than 10 mm Hg, while the other two had a preocclusion LVEDP of 6 and 8 mm Hg. Using linear regression analysis (Table 2), there was no significant correlation in change in LVEDP relative to patient age, body mass index, weight, body surface area, Qp : Qs, or preprocedure MPI. As compared with other variables, ASD device size did display greater correlation relative to change in LVEDP (R = 0.53, R2 = 0.28), although this still signifies a fairly weak correlation. No additional correlations were noted using regression analysis.
3 ASO, Amplatzer septal occluder; BMI, body mass index; BSA, body surface area; CAD, coronary artery disease; EDP, end diastolic pressure; GERD, gastroesophageal reflux disease; HCTZ, hydrochlorothiazide; HLD, hyperlipidemia; HTN, hypertension; LAD, left anterior descending; MPI, myocardial performance index; NA, no comorbid diagnoses; PCI, percutaneous coronary intervention; RA, rheumatoid arthritis; TIA, transient ischemic attack.
0.53 0.39 0.21 0.5 0.1 0.33 0.61 0.17 0.87 NA 0.42 0.35 0.31 0.27 NA NA NA NA NA 0.69 0.32 0.36 0.48 0.43 0.31 0.52 0.17 0.4 NA 0.77 0.05 0.13 0.31 NA NA NA NA NA 13 15 6 2 4 15 14 3 6 7 5 8 16 4 8 5 10 7 8 17 21 14 7 12 19 22 9 9 14 9 15 26 13 12 10 22 21 18 4 6 8 5 8 4 8 6 3 7 4 7 10 9 4 5 12 14 10 30 22 20 22 22 26 30 20 32 24 14 20 24 22 28 22 26 26 20 2.2 1.7 2.1 1.2 2.0 1.7 2.4 2.5 3.5 1.5 1.5 1.1 2.1 1.8 2.0 1.8 1.9 2.0 3.1 F F F F F F M F F F F F F F F F F M F 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
48 27 37 46 54 31 65 46 51 62 54 47 59 28 67 47 59 28 40
1.62 1.73 1.69 1.74 1.95 2.21 1.69 2.00 1.77 1.58 1.57 1.44 1.64 1.85 1.76 1.83 1.74 2.05 1.82
23.2 24.2 17.5 24.8 40.7 40.4 20.8 33.4 21.7 26.5 21.8 18.9 29.0 26.6 23.6 24.7 23.0 26.1 23.9
Aspirin None None None Diltiazem None None None Atenolol Candesartan None Aspirin None None None Levothyroxine Valsartan/HCTZ Clopidogrel, aspirin, amlodipine, pravastatin None
NA NA NA NA NA, HLD NA HTN HTN HTN HTN GERD NA NA Migraines Hypothyroid, TIA, RA Hypothryoid HTN CAD, s/p PCI LAD, HLD NA
ASO Size (cm) Preop Meds BMI BSA Age Gender Patient
Table 1.
Patient Characteristics with Atrial Septal Device Closure
Preop Diagnosis
Qp : Qs
Pre-EDP (mm Hg)
Post-EDP (mm Hg)
Delta EDP (mm Hg)
Pre-MPI
Post-MPI
LV Dysfunction with ASD Closure in Adults
During the hospital course, two of the 14 patients received intravenous furosemide due to postprocedure dyspnea. One patient who had history of hypertension received one dose of IV furosemide, and the second patient received three doses prior to discharge the following day. These patients, who were both 59 years old, had baseline LVEDPs of 10 and 12 mm Hg that increased after balloon occlusion to 22 and 26 mm Hg, respectively. Both patients were not on diuretic prior the procedure and went home the following day without any events. One patient had an episode of syncope in the hospital, and one patient had episode of chest pain overnight that after evaluation was felt to be atypical. One patient had atrial tachycardia occurring 3 weeks after the procedure, and she converted to sinus rhythm after overnight treatment with esmolol IV and digoxin. She was discharged on atenolol and digoxin without recurrence of arrhythmia. Discussion
ASDs are one of the most common forms of congenital heart disease diagnosed during adulthood. Often, closure is indicated due to large atrial shunts or for noncardiac indications (such as cryptogenic stroke). Currently, these are most commonly closed percutaneously in the cardiac catheterization laboratory with the ASO being most commonly used.6 Given the later age at diagnosis, older adult patients often exhibit chronic changes in LV hemodynamics (such as restrictive physiology).13,20 Previously, there has been some debate about closing those defects in patients with marked LV restriction or signs of abnormal filling hemodynamics. Most of the controversy for this approach stems from a small number of case studies discussing patients with complications following closure. Some investigators recommend prophylactic treatment with anticongestive therapy prior to device closure.16,17,21,22 Others have encouraged a cautious approach in those adults with high filling pressures: deferring closure or utilizing a fenestrated device.23 There has been some inconsistency in literature regarding what constitutes high filling pressures. One study pretreats all patients with diastolic dysfunction, whereas another study only pretreats in the setting of left atrial pressures greater than 10 mm Hg.17 Yet another study delays closure in those with LVEDP greater than 10 mm Hg during balloon test occlusion of the ASD.16 Age greater Congenit Heart Dis. 2014;••:••–••
4
Ermis et al.
Figure 1. Change in left ventricular end diastolic pressure following balloon occlusion of atrial septal defect.
Table 2.
Change in LVEDP and Correlative Factors Following Atrial Septal Device Closure
LVEDP
Mean Value Predevice
Mean Value Postdevice
7.1 mm Hg
15.3 mm Hg
Correlation Coefficient
P Value .5 .3 >.5 .09 >.5 >.5 >.5
LVEDP, left ventricular end diastolic pressure; BMI, body mass index; ASO, Amplatzer septal occluder; BSA, body surface area.
than 60 years has also indicated a need for pretreatment or device closure delay.21 In our study, we found that LVEDP increased in all patients following device closure. This finding is consistent with previously published data showing an immediate increase in mitral inflow following ASD closure. Pulmonary venous flow decreases, but the removal of the septal defect leads to increased mitral inflow and alteration of LV hemodynamics.24,25 Despite the fact that 10 (71%) patients could be labeled as high risk based on previous literature (age greater than 60 years, left atrial pressure greater than 10 mm Hg at baseline, or LVEDP greater than 10 mm Hg with defect occlusion), no patient in our study demonstrated significant heart failure symptoms, and only two patients required diuretics in the postprocedure period. Based on conventional risk factors (age, pre-LVEDP, post-LVEDP), these two patients had the highest preprocedure risk as they both were of increased age (59 years), had a relatively elevated LVEDP at baseline (10 and 12 mm Hg, respectively), and had an elevated Congenit Heart Dis. 2014;••:••–••
LVEDP after balloon sizing (22 and 26 mm Hg, respectively).
Speculation: LVEDP These findings are likely multifactorial relating to the particular patient population and the underlying postulated mechanisms for diastolic dysfunction in patients with ASDs. First, our population may be innately different than the previously reported populations. While LVEDP did increase following device closure, only one patient had an abnormal LVEDP (normal = 5–12 mm Hg) at baseline, and none were higher than 14 mm Hg. Five (36%) patients still had LVEDPs measuring within normal range after device closure. In addition, much of the recent literature supports the idea that LV diastolic dysfunction in the setting of right ventricular volume overload relates to geometric changes in the LV cavity and not actual LV myocardial stiffness.11,14,26–28 It has been speculated that this problem is of less concern in the younger patient because of increased LV elasticity in those patients.18,25 Thus, there is strong evidence in lit-
5
LV Dysfunction with ASD Closure in Adults erature that RV volumes rapidly decrease immediately following ASD closure.1,29–33 This should allow for the LV cavity to conform to a more conventional geometric shape following device closure. This rapid conformational change might allow for the LV to better accommodate the increased pressures due to shunt closure. This may be the case in spite of underlying LV myocardial noncompliance.
predicting which patients need closer monitoring. Periodically, postprocedure diuretic therapy may be indicated but should be reserved for symptomatic patients.
Speculation: MPI The MPI remained unchanged with a mean value of 0.39 postdevice compared with 0.38 prior to closure. Due to the small numbers present in this study (only 14 patients had MPI measurements available for comparison), it is difficult to draw conclusions from the data. That MPI remains unchanged despite a significant increase in LVEDP may relate to a performance reserve that might exist in these otherwise healthy individuals (i.e., the ability to tolerate the acute rise in LV pressures). This reasoning could explain the relatively benign course of even those patients with a marked increase in LVEDP following device closure. If this were true, MPI, as compared with LVEDP, may correlate more closely with clinical outcomes in this patient population. This is only speculative as MPI data were available in only one of the two patients in our study who required diuretics following closure. In addition, this patient’s MPI, despite increasing from 0.13 to 0.31, remained within a normal range following closure.
Wayne Franklin: Concept/design, data analysis/ interpretation, critical revision of the article, approval of the article.
Limitations Our results are limited due to the small number of patients, especially those requiring intervention. Our results also represent a specific cohort of adults with baseline LVEDPs less than 15 mm Hg and may not be applicable for patients with higher baseline pressures. In addition, there were no established criteria to determine the need for diuretic use as this was left up to the discretion of the individual cardiologist.
References
Conclusions
Percutaneous ASD closure induces a statistically significant acute increase in LV diastolic pressures, especially in those patients with a large ASD. This was found to be irrespective of patient age or degree of left-to-right shunting. Despite these changes, adults tolerate ASD closure in patients with an LVEDP < 15 prior to device closure. Preand post-LVEDP are important measurements in
Author Contributions Peter Ermis: Concept/design, data analysis/interpretation, drafting of the article, statistics, approval of the article.
Venkatachalam Mulukutla: Concept/design, data analysis/ interpretation, drafting of the article, statistics, approval of the article. Dhaval Parekh: Critical review of the article, data analysis/ interpretation, approval of the article. Frank Ing: Concept/design, data analysis/interpretation, critical revision of the article, approval of the article.
Corresponding Author: Peter Ermis, MD, Department of Pediatric Cardiology, Texas Children’s Hospital, MC WT 19345-C, Houston, TX 77030, USA. Tel: (1)832-826-5600; Fax: (1)832-826-1901; E-mail: [email protected] Conflict of interest: The authors of this study have no conflicts of interest or disclosures to report. Accepted in final form: June 9, 2014.
1 Jategaonkar S, Scholtz W, Schmidt H, Horstkotte D. Percutaneous closure of atrial septal defects: echocardiographic and functional results in patients older than 60 years. Circ Cardiovasc Interv. 2009;2 (2):85–89. 2 Rastogi N, Smeeton NC, Qureshi SA. Factors related to successful transcatheter closure of atrial septal defects using the Amplatzer septal occluder. Pediatr Cardiol. 2009;30 (7):888–892. 3 Kaya MG, Baykan A, Dogan A, et al. Intermediateterm effects of transcatheter secundum atrial septal defect closure on cardiac remodeling in children and adults. Pediatr Cardiol. 2010;31 (4):474–482. 4 Gatzoulis MA, Redington AN, Somerville J, Shore DF. Should atrial septal defects in adults be closed. Ann Thorac Surg. 1996;61 (2):657–659. 5 Khan AA, Tan JL, Li W, et al. The impact of transcatheter atrial septal defect closure in the older population: a prospective study. JACC Cardiovasc Interv. 2010;3 (3):276–281. 6 Abd El Rahman M, Hui W, Timme J, et al. Analysis of atrial and ventricular performance by tissue Congenit Heart Dis. 2014;••:••–••
6
7 8
9
10
11
12
13
14
15 16
17
18
19
Ermis et al. Doppler imaging in patients with atrial septal defects before and after surgical and catheter closure. Echocardiography. 2005;22 (7):579–585. Al-Hindi A, Cao Q, Hijazi Z. Transcatheter closure of secundum atrial septal defect in the elderly. J Invasive Cardiol. 2009;21 (2):70–75. Everett AD, Jennings J, Sibinga E, et al. Community use of the Amplatzer atrial septal defect occluder: results of the multicenter MAGIC atrial septal defect study. Pediatr Cardiol. 2008;30 (3):240–247. Masura J, Gavora P, Formanek A, Hijazi ZM. Transcatheter closure of secundum atrial septal defects using the new self-centering Amplatzer septal occluder: initial human experience. Cathet Cardiovasc Diagn. 1997;42:388–393. Mainzer G, Braver Y, Khoury A, et al. Morphologic, mechanical, conductive, and hemodynamic changes following transcatheter closure of atrial septal defect. Congenit Heart Dis. 2010;5 (1):25–31. Pascotto M, Santoro G, Cerrato F, et al. Timecourse of cardiac remodeling following transcatheter closure of atrial septal defect. Int J Cardiol. 2006;112 (3):348–352. Majunke N, Bialkowski J, Wilson N, et al. Closure of atrial septal defect with the Amplatzer septal occluder in adults. Am J Cardiol. 2009;103 (4):550– 554. Tomai F, Gaspardone A, Papa M, Polisca P. Acute left ventricular failure after transcatheter closure of a secundum atrial septal defect in a patient with coronary artery disease: a critical reappraisal. Catheter Cardiovasc Interv. 2002;55 (1):97–99. Carabello BA, Gash A, Mayers D, Spann JF. Normal left ventricular systolic function in adults with atrial septal defect and left heart failure. Am J Cardiol. 1982;49 (8):1868–1873. Davies H, Oliver G, Rappoport W, Gazetopoulos N. Abnormal left heart function after operation for atrial septal defect. Br Heart J. 1970;32 (6):747–753. Schubert S, Peters B, Abdul-Khaliq H, Nagdyman N, Lange P, Ewert P. Left ventricular conditioning in the elderly patient to prevent congestive heart failure after transcatheter closure of atrial septal defect. Catheter Cardiovasc Interv. 2005;64 (3):333– 337. Ewert P, Berger F, Nagdyman N, et al. Masked left ventricular restriction in elderly patients with atrial septal defects: a contraindication for closure? Catheter Cardiovasc Interv. 2001;52:177–189. Kenny D, Cao Q, Hijazi Z. Fenestration of a gore helix septal occluder device in a patient with diastolic dysfunction of the left ventricle. Catheter Cardiovasc Interv. 2011;78:594–598. Holzer R, Cao Q, Hijazi Z. Closure of a moderately large atrial septal defect with a self-fabricated Amplatzer occluder in an 85-year-old patient with reduced diastolic elasticity of the left ventricle. Catheter Cardiovasc Interv. 2005;64:513–518.
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20 Rao PS, Lorch S. Left ventricular function after percutaneous occlusion of atrial septal defects. Echocardiography. 2010;27 (3):351–353. 21 Swan L, Varma C, Yip J, et al. Transcatheter device closure of atrial septal defects in the elderly: technical considerations and short-term outcomes. Int J Cardiol. 2006;107 (2):207–210. 22 Masutani S, Senzaki H. Left ventricular function in adult patients with atrial septal defect: implication for development of heart failure after transcatheter closure. J Card Fail. 2011;17 (11):957–963. 23 MacDonald ST, Arcidiacono C, Butera G. Fenestrated Amplatzer atrial septal defect occluder in an elderly patient with restrictive left ventricular physiology. Heart. 2010;97 (5):438–438. 24 Masutani S, Taketazu M, Mihara C, et al. Usefulness of early diastolic mitral annular velocity to predict plasma levels of brain natriuretic peptide and transient heart failure development after device closure of atrial septal defect. Am J Cardiol. 2009;104 (12):1732–1736. 25 Lin WW, Fu YC, Jan SL, et al. Immediate change in pulmonary venous flow pattern after deployment of occluder device for atrial septal defect. Echocardiography. 2009;26 (4):452–458. 26 Pascotto M, Santoro G, Caso P, et al. Global and regional left ventricular function in patients undergoing transcatheter closure of secundum atrial septal defect. Am J Cardiol. 2005;96 (3):439–442. 27 Booth DC, Wisenbaugh T, Smith M, DeMaria AN. Left ventricular distensibility and passive elastic stiffness in atrial septal defect. J Am Coll Cardiol. 1988;12 (5):1231–1236. 28 Walker RE, Moran AM, Gauvreau K, Colan SD. Evidence of adverse ventricular interdependence in patients with atrial septal defects. Am J Cardiol. 2004;93:1374–1377. 29 Brochu M-C. Improvement in exercise capacity in asymptomatic and mildly symptomatic adults after atrial septal defect percutaneous closure. Circulation. 2002;106 (14):1821–1826. 30 Shaheen J, Alper L, Rosenmann D, et al. Effect of surgical repair of secundum-type atrial septal defect on right atrial, right ventricular, and left ventricular volumes in adults. Am J Cardiol. 2000;86:1395–1397. 31 Wu ET, Akagi T, Taniguchi M, et al. Differences in right and left ventricular remodeling after transcatheter closure of atrial septal defect among adults. Catheter Cardiovasc Interv. 2007;69 (6):866–871. 32 Du Z-D, Cao Q-L, Koenig P, Heitschmidt M, Hijazi Z. Speed of normalization of right ventricluar volume overload after transcather closure of atrial septal defect in childrens and adults. J Am Coll Cardiol. 2001;88:1450–1453. 33 Altindag T, Roos-Hesselink J, Cuypers J, et al. Transcatheter device closure of atrial septal defects in patients aged 40 years and older. Neth Heart J. 2010;18 (11):537–542.
ORIGINAL ARTICLE Left Ventricular Hemodynamic Changes and Clinical Outcomes after Transcatheter Atrial Septal Defect Closure in Adults Peter Ermis, MD,* Wayne Franklin, MD,* Venkatachalam Mulukutla, MD,* Dhaval Parekh, MD,* and Frank Ing, MD† *Department of Pediatric Cardiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, Tex, USA; † Department of Pediatric Cardiology, Children’s Hospital of Los Angeles, Los Angeles, Calif, USA ABSTRACT
Objectives. The objectives of this study are to assess current management algorithms for left ventricular (LV) hemodynamic and diastolic changes following atrial septal device occlusion in adult patients. Background. Percutaneous closure is now routine for atrial septal defects (ASDs). Previous studies show ventricular size normalization following percutaneous closure. Case reports have discussed the incidence of early LV dysfunction following ASD device placement with some recommending delay of closure or placement of a fenestrated device in patients with elevated LV pressures. Method. All adult patients with an isolated secundum ASD who underwent percutaneous repair were included in this study. In addition to placement of the Amplatzer septal occluder, all patients had a pre and postprocedure transthoracic echocardiography performed measuring myocardial performance index (MPI). Left ventricular end diastolic pressure (LVEDP) was measured before and after balloon occlusion. Results. Nineteen patients (17 female and two male) were included in this study. Average age was 47.2 years (± 12.7 years). All defects were of clinical significance with average Qp : Qs = 2.0 (± 0.6). Balloon occlusion led to a significant (P < .01) increase in LVEDP (pre-LVEDP mean = 7.1 mm Hg, post-LVEDP mean = 15.3 mm Hg). There was no significant change in MPI. ASD device size displayed a modest correlation relative to the change in LVEDP (R = 0.42, P = .09). Conclusions. Percutaneous ASD closure induces an increase in LVEDP. Despite this, all patients tolerated device closure without complication. It appears safe to close ASDs in these patients. Key Words. Adult Congenital Heart Disease; Atrial Septal Defect; Percutaneous Catheter Intervention
Introduction
S
ecundum atrial septal defects (ASDs) account for 7–12% of all congenital heart disease in childhood and up to 22% in the adult population.1–3 While the majority of children are asymptomatic, most adults present with symptoms such as exercise intolerance, dyspnea, or palpitations.4 Closure of ASDs has been shown to result in a significant decrease in symptoms and exercise improvements.3,5 First demonstrated by King and Mills in the 1970s, ASDs are now routinely closed via an intravascular transcatheter approach using a variety of occlusion devices. Since its introduction in the 1990s, the Amplatzer septal occluder (ASO) © 2014 Wiley Periodicals, Inc.
(St. Jude Medical, St. Paul, MN, USA) is now the most commonly used device for these percutaneous interventions. The ASO is one of only two devices approved by the Federal Drug Administration (FDA) for ASD closure.6–9 Previous studies show right and left ventricular (LV) size improvement by echocardiographic assessment within 24 hours following percutaneous closure and normalization of biventricular size within 1 year.1,3,5,10,11 A small number of studies have discussed the incidence of early LV dysfunction following device placement in adults. Also, it is widely accepted that LV diastolic function decreases with age. Several case reports have discussed early ventricular dysfunction following Congenit Heart Dis. 2014;••:••–••
2 device closure in patients with known restrictive LV physiology.1,11–15 Some authors have reported LV conditioning with diuretics (primarily furosemide therapy) or dopamine prior to ASD closure in the patient with a markedly restrictive LV.16,17 Other studies have reported closure with fenestrated occluder devices in these patients.18,19 We hypothesized that an abrupt cessation of left to right atrial level shunting at the time of device closure will lead to an acute increase in LV end diastolic pressures (LVEDP), especially in the elderly patient with decreased LV compliance, left atrial hypertension, and pulmonary edema. We believe that this acute change in hemodynamics will be represented by an increase in signs of volume overload following device placement. No observational studies have reported direct measurements of LV pressure to evaluate acute hemodynamic changes following percutaneous ASD repair. Our study directly measures LVEDP before and after ASD occlusion. Materials and Methods
All adult patients under the care of the Adult Congenital Heart Disease Service with an isolated secundum ASD who underwent percutaneous repair at our institution from November 2006 to November 2010 were prospectively included in this study. All hospital records and catheterization reports were reviewed. All ASDs were closed using standard technique. The catheterization procedures utilized conscious sedation with fentanyl and versed. A right heart catheterization was completed and saturations obtained to calculate Qp : Qs. Afterward, a pigtail catheter was advanced to the LV, and LVEDP was measured. Then, a sizing balloon was used to occlude the defect, and the LVEDP measurements once again were recorded. Using the assistance of intracardiac echocardiography, the ASD was closed. In addition to ASD closure, patients had pre and postprocedure transthoracic echocardiography performed to record mitral inflow and LV outflow tract Doppler measurements. Myocardial performance index (MPI; MPI = isovolemic contraction time + isovolemic relaxation time/ejection time) was measured before and after device implantation via transthoracic echocardiographic Doppler measurements. Institutional review board approval was obtained for this study. Statistical analysis was performed using spss (IBM SPSS Statistics, Chicago, IL, USA). The paired Student t-test was perCongenit Heart Dis. 2014;••:••–••
Ermis et al. formed to determine statistical differences in measurement over time. Linear regression analysis and analysis of variance (ANOVA) were utilized to calculate correlation factors. A P value of less than .05 was considered statistically significant.
Results
Nineteen patients (Table 1) were included in this study. Mean age was 47.2 years (± 12.7) with an average body mass index of 25.8 (± 6.3). Of the 19 patients, six patients had a medical history of hypertension, two patients had hyperlipidemia, one patient had history of stroke, one patient with hypothyroidism, and one patient had a history of coronary artery disease with previous percutaneous coronary intervention to the left anterior descending (Table 1). No additional comorbid medical conditions were present. None of the patients had LV hypertrophy by preoperative transthoracic echocardiogram, calculated by standard measurements. The mean Qp : Qs was 2.0 (± 0.6). The median septal defect size as measured by static balloon sizing under fluoroscopy and intracardiac echocardiography was 22 mm (14–29) and 20 mm (12.5– 28.5), respectively. The median ASO size device implanted was 20 mm (14–30). No fenestrated devices were implanted. Pre- and postocclusion LVEDP measurements were available in all patients while pre- and postocclusion MPI measurements were available in 14 of the 19 patients. The decreased number of MPI data relates to those studies having inadequate echo images obtained to properly make this measurement. The mean LVEDP increased from 7.1 to 15.3 mm Hg after device occlusion, which was statistically significant (P < .01) (Figure 1). The MPI, however, did not display a statistically significant change. A total of five patients had an LVEDP after balloon occlusion that was greater than 20 mm Hg. Three of these patients had a preocclusion LVEDP of greater than 10 mm Hg, while the other two had a preocclusion LVEDP of 6 and 8 mm Hg. Using linear regression analysis (Table 2), there was no significant correlation in change in LVEDP relative to patient age, body mass index, weight, body surface area, Qp : Qs, or preprocedure MPI. As compared with other variables, ASD device size did display greater correlation relative to change in LVEDP (R = 0.53, R2 = 0.28), although this still signifies a fairly weak correlation. No additional correlations were noted using regression analysis.
3 ASO, Amplatzer septal occluder; BMI, body mass index; BSA, body surface area; CAD, coronary artery disease; EDP, end diastolic pressure; GERD, gastroesophageal reflux disease; HCTZ, hydrochlorothiazide; HLD, hyperlipidemia; HTN, hypertension; LAD, left anterior descending; MPI, myocardial performance index; NA, no comorbid diagnoses; PCI, percutaneous coronary intervention; RA, rheumatoid arthritis; TIA, transient ischemic attack.
0.53 0.39 0.21 0.5 0.1 0.33 0.61 0.17 0.87 NA 0.42 0.35 0.31 0.27 NA NA NA NA NA 0.69 0.32 0.36 0.48 0.43 0.31 0.52 0.17 0.4 NA 0.77 0.05 0.13 0.31 NA NA NA NA NA 13 15 6 2 4 15 14 3 6 7 5 8 16 4 8 5 10 7 8 17 21 14 7 12 19 22 9 9 14 9 15 26 13 12 10 22 21 18 4 6 8 5 8 4 8 6 3 7 4 7 10 9 4 5 12 14 10 30 22 20 22 22 26 30 20 32 24 14 20 24 22 28 22 26 26 20 2.2 1.7 2.1 1.2 2.0 1.7 2.4 2.5 3.5 1.5 1.5 1.1 2.1 1.8 2.0 1.8 1.9 2.0 3.1 F F F F F F M F F F F F F F F F F M F 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
48 27 37 46 54 31 65 46 51 62 54 47 59 28 67 47 59 28 40
1.62 1.73 1.69 1.74 1.95 2.21 1.69 2.00 1.77 1.58 1.57 1.44 1.64 1.85 1.76 1.83 1.74 2.05 1.82
23.2 24.2 17.5 24.8 40.7 40.4 20.8 33.4 21.7 26.5 21.8 18.9 29.0 26.6 23.6 24.7 23.0 26.1 23.9
Aspirin None None None Diltiazem None None None Atenolol Candesartan None Aspirin None None None Levothyroxine Valsartan/HCTZ Clopidogrel, aspirin, amlodipine, pravastatin None
NA NA NA NA NA, HLD NA HTN HTN HTN HTN GERD NA NA Migraines Hypothyroid, TIA, RA Hypothryoid HTN CAD, s/p PCI LAD, HLD NA
ASO Size (cm) Preop Meds BMI BSA Age Gender Patient
Table 1.
Patient Characteristics with Atrial Septal Device Closure
Preop Diagnosis
Qp : Qs
Pre-EDP (mm Hg)
Post-EDP (mm Hg)
Delta EDP (mm Hg)
Pre-MPI
Post-MPI
LV Dysfunction with ASD Closure in Adults
During the hospital course, two of the 14 patients received intravenous furosemide due to postprocedure dyspnea. One patient who had history of hypertension received one dose of IV furosemide, and the second patient received three doses prior to discharge the following day. These patients, who were both 59 years old, had baseline LVEDPs of 10 and 12 mm Hg that increased after balloon occlusion to 22 and 26 mm Hg, respectively. Both patients were not on diuretic prior the procedure and went home the following day without any events. One patient had an episode of syncope in the hospital, and one patient had episode of chest pain overnight that after evaluation was felt to be atypical. One patient had atrial tachycardia occurring 3 weeks after the procedure, and she converted to sinus rhythm after overnight treatment with esmolol IV and digoxin. She was discharged on atenolol and digoxin without recurrence of arrhythmia. Discussion
ASDs are one of the most common forms of congenital heart disease diagnosed during adulthood. Often, closure is indicated due to large atrial shunts or for noncardiac indications (such as cryptogenic stroke). Currently, these are most commonly closed percutaneously in the cardiac catheterization laboratory with the ASO being most commonly used.6 Given the later age at diagnosis, older adult patients often exhibit chronic changes in LV hemodynamics (such as restrictive physiology).13,20 Previously, there has been some debate about closing those defects in patients with marked LV restriction or signs of abnormal filling hemodynamics. Most of the controversy for this approach stems from a small number of case studies discussing patients with complications following closure. Some investigators recommend prophylactic treatment with anticongestive therapy prior to device closure.16,17,21,22 Others have encouraged a cautious approach in those adults with high filling pressures: deferring closure or utilizing a fenestrated device.23 There has been some inconsistency in literature regarding what constitutes high filling pressures. One study pretreats all patients with diastolic dysfunction, whereas another study only pretreats in the setting of left atrial pressures greater than 10 mm Hg.17 Yet another study delays closure in those with LVEDP greater than 10 mm Hg during balloon test occlusion of the ASD.16 Age greater Congenit Heart Dis. 2014;••:••–••
4
Ermis et al.
Figure 1. Change in left ventricular end diastolic pressure following balloon occlusion of atrial septal defect.
Table 2.
Change in LVEDP and Correlative Factors Following Atrial Septal Device Closure
LVEDP
Mean Value Predevice
Mean Value Postdevice
7.1 mm Hg
15.3 mm Hg
Correlation Coefficient
P Value .5 .3 >.5 .09 >.5 >.5 >.5
LVEDP, left ventricular end diastolic pressure; BMI, body mass index; ASO, Amplatzer septal occluder; BSA, body surface area.
than 60 years has also indicated a need for pretreatment or device closure delay.21 In our study, we found that LVEDP increased in all patients following device closure. This finding is consistent with previously published data showing an immediate increase in mitral inflow following ASD closure. Pulmonary venous flow decreases, but the removal of the septal defect leads to increased mitral inflow and alteration of LV hemodynamics.24,25 Despite the fact that 10 (71%) patients could be labeled as high risk based on previous literature (age greater than 60 years, left atrial pressure greater than 10 mm Hg at baseline, or LVEDP greater than 10 mm Hg with defect occlusion), no patient in our study demonstrated significant heart failure symptoms, and only two patients required diuretics in the postprocedure period. Based on conventional risk factors (age, pre-LVEDP, post-LVEDP), these two patients had the highest preprocedure risk as they both were of increased age (59 years), had a relatively elevated LVEDP at baseline (10 and 12 mm Hg, respectively), and had an elevated Congenit Heart Dis. 2014;••:••–••
LVEDP after balloon sizing (22 and 26 mm Hg, respectively).
Speculation: LVEDP These findings are likely multifactorial relating to the particular patient population and the underlying postulated mechanisms for diastolic dysfunction in patients with ASDs. First, our population may be innately different than the previously reported populations. While LVEDP did increase following device closure, only one patient had an abnormal LVEDP (normal = 5–12 mm Hg) at baseline, and none were higher than 14 mm Hg. Five (36%) patients still had LVEDPs measuring within normal range after device closure. In addition, much of the recent literature supports the idea that LV diastolic dysfunction in the setting of right ventricular volume overload relates to geometric changes in the LV cavity and not actual LV myocardial stiffness.11,14,26–28 It has been speculated that this problem is of less concern in the younger patient because of increased LV elasticity in those patients.18,25 Thus, there is strong evidence in lit-
5
LV Dysfunction with ASD Closure in Adults erature that RV volumes rapidly decrease immediately following ASD closure.1,29–33 This should allow for the LV cavity to conform to a more conventional geometric shape following device closure. This rapid conformational change might allow for the LV to better accommodate the increased pressures due to shunt closure. This may be the case in spite of underlying LV myocardial noncompliance.
predicting which patients need closer monitoring. Periodically, postprocedure diuretic therapy may be indicated but should be reserved for symptomatic patients.
Speculation: MPI The MPI remained unchanged with a mean value of 0.39 postdevice compared with 0.38 prior to closure. Due to the small numbers present in this study (only 14 patients had MPI measurements available for comparison), it is difficult to draw conclusions from the data. That MPI remains unchanged despite a significant increase in LVEDP may relate to a performance reserve that might exist in these otherwise healthy individuals (i.e., the ability to tolerate the acute rise in LV pressures). This reasoning could explain the relatively benign course of even those patients with a marked increase in LVEDP following device closure. If this were true, MPI, as compared with LVEDP, may correlate more closely with clinical outcomes in this patient population. This is only speculative as MPI data were available in only one of the two patients in our study who required diuretics following closure. In addition, this patient’s MPI, despite increasing from 0.13 to 0.31, remained within a normal range following closure.
Wayne Franklin: Concept/design, data analysis/ interpretation, critical revision of the article, approval of the article.
Limitations Our results are limited due to the small number of patients, especially those requiring intervention. Our results also represent a specific cohort of adults with baseline LVEDPs less than 15 mm Hg and may not be applicable for patients with higher baseline pressures. In addition, there were no established criteria to determine the need for diuretic use as this was left up to the discretion of the individual cardiologist.
References
Conclusions
Percutaneous ASD closure induces a statistically significant acute increase in LV diastolic pressures, especially in those patients with a large ASD. This was found to be irrespective of patient age or degree of left-to-right shunting. Despite these changes, adults tolerate ASD closure in patients with an LVEDP < 15 prior to device closure. Preand post-LVEDP are important measurements in
Author Contributions Peter Ermis: Concept/design, data analysis/interpretation, drafting of the article, statistics, approval of the article.
Venkatachalam Mulukutla: Concept/design, data analysis/ interpretation, drafting of the article, statistics, approval of the article. Dhaval Parekh: Critical review of the article, data analysis/ interpretation, approval of the article. Frank Ing: Concept/design, data analysis/interpretation, critical revision of the article, approval of the article.
Corresponding Author: Peter Ermis, MD, Department of Pediatric Cardiology, Texas Children’s Hospital, MC WT 19345-C, Houston, TX 77030, USA. Tel: (1)832-826-5600; Fax: (1)832-826-1901; E-mail: [email protected] Conflict of interest: The authors of this study have no conflicts of interest or disclosures to report. Accepted in final form: June 9, 2014.
1 Jategaonkar S, Scholtz W, Schmidt H, Horstkotte D. Percutaneous closure of atrial septal defects: echocardiographic and functional results in patients older than 60 years. Circ Cardiovasc Interv. 2009;2 (2):85–89. 2 Rastogi N, Smeeton NC, Qureshi SA. Factors related to successful transcatheter closure of atrial septal defects using the Amplatzer septal occluder. Pediatr Cardiol. 2009;30 (7):888–892. 3 Kaya MG, Baykan A, Dogan A, et al. Intermediateterm effects of transcatheter secundum atrial septal defect closure on cardiac remodeling in children and adults. Pediatr Cardiol. 2010;31 (4):474–482. 4 Gatzoulis MA, Redington AN, Somerville J, Shore DF. Should atrial septal defects in adults be closed. Ann Thorac Surg. 1996;61 (2):657–659. 5 Khan AA, Tan JL, Li W, et al. The impact of transcatheter atrial septal defect closure in the older population: a prospective study. JACC Cardiovasc Interv. 2010;3 (3):276–281. 6 Abd El Rahman M, Hui W, Timme J, et al. Analysis of atrial and ventricular performance by tissue Congenit Heart Dis. 2014;••:••–••
6
7 8
9
10
11
12
13
14
15 16
17
18
19
Ermis et al. Doppler imaging in patients with atrial septal defects before and after surgical and catheter closure. Echocardiography. 2005;22 (7):579–585. Al-Hindi A, Cao Q, Hijazi Z. Transcatheter closure of secundum atrial septal defect in the elderly. J Invasive Cardiol. 2009;21 (2):70–75. Everett AD, Jennings J, Sibinga E, et al. Community use of the Amplatzer atrial septal defect occluder: results of the multicenter MAGIC atrial septal defect study. Pediatr Cardiol. 2008;30 (3):240–247. Masura J, Gavora P, Formanek A, Hijazi ZM. Transcatheter closure of secundum atrial septal defects using the new self-centering Amplatzer septal occluder: initial human experience. Cathet Cardiovasc Diagn. 1997;42:388–393. Mainzer G, Braver Y, Khoury A, et al. Morphologic, mechanical, conductive, and hemodynamic changes following transcatheter closure of atrial septal defect. Congenit Heart Dis. 2010;5 (1):25–31. Pascotto M, Santoro G, Cerrato F, et al. Timecourse of cardiac remodeling following transcatheter closure of atrial septal defect. Int J Cardiol. 2006;112 (3):348–352. Majunke N, Bialkowski J, Wilson N, et al. Closure of atrial septal defect with the Amplatzer septal occluder in adults. Am J Cardiol. 2009;103 (4):550– 554. Tomai F, Gaspardone A, Papa M, Polisca P. Acute left ventricular failure after transcatheter closure of a secundum atrial septal defect in a patient with coronary artery disease: a critical reappraisal. Catheter Cardiovasc Interv. 2002;55 (1):97–99. Carabello BA, Gash A, Mayers D, Spann JF. Normal left ventricular systolic function in adults with atrial septal defect and left heart failure. Am J Cardiol. 1982;49 (8):1868–1873. Davies H, Oliver G, Rappoport W, Gazetopoulos N. Abnormal left heart function after operation for atrial septal defect. Br Heart J. 1970;32 (6):747–753. Schubert S, Peters B, Abdul-Khaliq H, Nagdyman N, Lange P, Ewert P. Left ventricular conditioning in the elderly patient to prevent congestive heart failure after transcatheter closure of atrial septal defect. Catheter Cardiovasc Interv. 2005;64 (3):333– 337. Ewert P, Berger F, Nagdyman N, et al. Masked left ventricular restriction in elderly patients with atrial septal defects: a contraindication for closure? Catheter Cardiovasc Interv. 2001;52:177–189. Kenny D, Cao Q, Hijazi Z. Fenestration of a gore helix septal occluder device in a patient with diastolic dysfunction of the left ventricle. Catheter Cardiovasc Interv. 2011;78:594–598. Holzer R, Cao Q, Hijazi Z. Closure of a moderately large atrial septal defect with a self-fabricated Amplatzer occluder in an 85-year-old patient with reduced diastolic elasticity of the left ventricle. Catheter Cardiovasc Interv. 2005;64:513–518.
Congenit Heart Dis. 2014;••:••–••
20 Rao PS, Lorch S. Left ventricular function after percutaneous occlusion of atrial septal defects. Echocardiography. 2010;27 (3):351–353. 21 Swan L, Varma C, Yip J, et al. Transcatheter device closure of atrial septal defects in the elderly: technical considerations and short-term outcomes. Int J Cardiol. 2006;107 (2):207–210. 22 Masutani S, Senzaki H. Left ventricular function in adult patients with atrial septal defect: implication for development of heart failure after transcatheter closure. J Card Fail. 2011;17 (11):957–963. 23 MacDonald ST, Arcidiacono C, Butera G. Fenestrated Amplatzer atrial septal defect occluder in an elderly patient with restrictive left ventricular physiology. Heart. 2010;97 (5):438–438. 24 Masutani S, Taketazu M, Mihara C, et al. Usefulness of early diastolic mitral annular velocity to predict plasma levels of brain natriuretic peptide and transient heart failure development after device closure of atrial septal defect. Am J Cardiol. 2009;104 (12):1732–1736. 25 Lin WW, Fu YC, Jan SL, et al. Immediate change in pulmonary venous flow pattern after deployment of occluder device for atrial septal defect. Echocardiography. 2009;26 (4):452–458. 26 Pascotto M, Santoro G, Caso P, et al. Global and regional left ventricular function in patients undergoing transcatheter closure of secundum atrial septal defect. Am J Cardiol. 2005;96 (3):439–442. 27 Booth DC, Wisenbaugh T, Smith M, DeMaria AN. Left ventricular distensibility and passive elastic stiffness in atrial septal defect. J Am Coll Cardiol. 1988;12 (5):1231–1236. 28 Walker RE, Moran AM, Gauvreau K, Colan SD. Evidence of adverse ventricular interdependence in patients with atrial septal defects. Am J Cardiol. 2004;93:1374–1377. 29 Brochu M-C. Improvement in exercise capacity in asymptomatic and mildly symptomatic adults after atrial septal defect percutaneous closure. Circulation. 2002;106 (14):1821–1826. 30 Shaheen J, Alper L, Rosenmann D, et al. Effect of surgical repair of secundum-type atrial septal defect on right atrial, right ventricular, and left ventricular volumes in adults. Am J Cardiol. 2000;86:1395–1397. 31 Wu ET, Akagi T, Taniguchi M, et al. Differences in right and left ventricular remodeling after transcatheter closure of atrial septal defect among adults. Catheter Cardiovasc Interv. 2007;69 (6):866–871. 32 Du Z-D, Cao Q-L, Koenig P, Heitschmidt M, Hijazi Z. Speed of normalization of right ventricluar volume overload after transcather closure of atrial septal defect in childrens and adults. J Am Coll Cardiol. 2001;88:1450–1453. 33 Altindag T, Roos-Hesselink J, Cuypers J, et al. Transcatheter device closure of atrial septal defects in patients aged 40 years and older. Neth Heart J. 2010;18 (11):537–542.
