ADVERTISEMENT
Safety and Efficacy of Transcatheter Closure of Patent Ductus Arteriosus With Severe Mitral Regurgitation in Adults
Abstract: Background. Transcatheter closure is the usual treatment for patent ductus arteriosus (PDA), but its safety and efficacy have not been reported in adult PDA patients with severe mitral regurgitation. Study design. A retrospective study on 27 consecutive patients diagnosed with PDA and severe mitral regurgitation and treated using transcatheter closure between September 2010 and September 2012 at the Department of Cardiology of Changhai Hospital in Changhai, China. Left ventricular (LV) diastolic volume and function, pulmonary artery pressure, and instantaneous reverse-flow volume were examined by echocardiography before PDA closure, immediately after closure, and 1 year after closure. Results. After the procedure, the LV diastolic volume (P<.05) and instantaneous reverse-flow volume (P<.001) were significantly decreased. There was no effect on the ejection fraction (P>.05). Pulmonary arterial systolic pressure was unchanged 1 year after closure (from 46.41 ± 19.92 mm Hg to 45.43 ± 13.64 mm Hg; P=.58). All procedures were uneventful and only mild complications occurred (hemolysis in 2 cases, subcutaneous hematoma in 4 cases, and fever in 2 cases). Conclusion. Transcatheter closure can decrease the LV volume and instantaneous reverse-flow volume in adult PDA patients with severe mitral regurgitation. This procedure is effective and has a good safety profile.
J INVASIVE CARDIOL 2016;28(1):30-33
Key words: congenital heart disease, patent ductus arteriosus, transcatheter closure
_____________________________________
Patent ductus arteriosus (PDA) is common and accounts for 6%-11% of all congenital heart disease.1,2 Left-to-right shunting through the ductus may result in left ventricular (LV) overload and remodeling.3 Structural changes of the heart and stretching of the mitral annulus and chordal apparatus eventually lead to mitral regurgitation.4 PDA complicated with severe mitral regurgitation is not rare, and is commonly treated with open-heart surgery.5,6 Although open-heart surgery has a minimal operative mortality, some risks still exist, including residual shunting, surgical trauma, cardiopulmonary bypass, postpericardiotomy syndrome, and wound infection.
Transcatheter PDA closure has been proven an effective and less invasive option, with good outcomes.7-10 Presently, transcatheter PDA closure is the standard therapy for PDA due to reduced surgical procedure-related complications and length of hospital stay. However, the efficacy of transcatheter closure for PDA complicated with severe mitral regurgitation has not been investigated, except in a few anecdotal single case reports.11-14
Therefore, the aim of the present study was to evaluate the immediate and 1-year outcomes of transcatheter PDA closure in adult patients with severe mitral regurgitation by retrospectively examining the hemodynamics, echocardiography, and complications of a 27-patient study group. The results of the present study could allow the treatment of these patients using a less morbid approach.
Methods
Patients. We collected the data from consecutive adult patients who were diagnosed with PDA at the Department of Cardiology, Changhai Hospital in Changhai, China between September 2010 and September 2012. The indication for PDA closure at our institution is either systolic or continuous murmur and PDA presence confirmed by echocardiography. The inclusion criteria were: (1) age ≥15 years; (2) mitral regurgitant fraction >50%; (3) patients who refused open-heart surgery; and (4) life expectancy >1 year. Patients were excluded from the study if they had: (1) history of endocarditis; (2) history of cardiac surgery; (3) recent myocardial infarction (within 3 months); (4) severe pulmonary hypertension with right-to-left shunt and pulmonary resistance >14 Wood units; and (5) recent embolic events within 30 days. This study was approved by the Ethics Committee of our Medical University. Written informed consent was obtained from the patients or their guardians.
Echocardiography. Echocardiography was performed with the patient lying in the supine position or left lateral semirecumbent position. All echocardiographic examinations were carried out by a single observer (Dr Chen) using the Acuson Sequoia C256 echocardiography system (Siemens). Data were saved for later analysis. An electrocardiographic tracing was recorded simultaneously. Standard parasternal, apical, and subcostal views were used to detect any additional cardiac abnormality in the PDA patients.
The degree of severity of mitral regurgitation was shown by the regurgitant fraction, which is the percentage of the LV stroke volume that regurgitates into the left atrium and is calculated as: (Vmitral – Vaortic) / Vmitral × 100%, where Vmitral is the blood volume through the mitral valve during ventricular diastole and Vaortic is the blood volume through the aortic valve during ventricular systole. We recorded the regurgitant fraction as ranked data, to provide quantitative data. We defined the level of mitral regurgitation according to Zoghbi et al.15 Severe mitral regurgitation was defined as a regurgitant fraction >50%.15
Cardiac catheterization. Cardiac catheterization was performed to close the PDA using a percutaneous device (Shape Memory Alloy PDA occlusion devices; Shanghai Shape Memory Alloy Material Co, Ltd) under local anesthesia with systemic heparinization and prophylactic intravenous cefradine. Pressure and saturation measurements of the LV, aortic arch, and main pulmonary artery were recorded before occlusion of the PDA. Angiography was performed in the distal aortic arch before and after PDA occlusion.
Aspirin 100 mg/day was administered after the procedure for 6 months to prevent thrombosis. Transesophageal echocardiography and x-ray were performed at 7 days, 30 days, 90 days, and 1 year post PDA closure. The patients were followed by telephone at 1 month post procedure and at the outpatient clinic at 3 months and 1 year post procedure.
Statistical analysis. Statistical analysis was performed using SPSS 17.0 (SPSS, Inc). Normally distributed continuous variables are expressed as mean ± standard deviation, and were compared using the Student’s t-test. Non-normally distributed continuous variables are expressed as median and interquartile range (IQR), and were compared using the Wilcoxon-Mann-Whitney test. Categorical data were compared using the chi-square test. P-values <.05 were considered statistically significant.
Results
Patient characteristics. The baseline characteristics and clinical features of the 27 patients are presented in Table 1. Mean age was 41.0 ± 2.6 years. PDA size was 8.67 ± 4.49 mm. PDA shape was tubular in 9 patients (33.3%), funnel-like in 13 patients (48.1%), window-like in 4 patients (14.8%), and mushroom-like in 1 patient (3.7%). Left atrium diameter was 4.46 ± 0.75 cm, left ventricular end-systolic diameter was 4.69 ± 0.84 cm, and left ventricular end-diastolic diameter was 6.24 ± 0.84 cm. Ejection fraction value was 52.46 ± 9.05%. Pulmonary arterial systolic pressure was 47.59 ± 22.14 mm Hg. Body mass index (BMI) was 22.86 ± 2.64 kg/m2. Seven patients (25.9%) suffered from hypertension (2 patients [7.4%] from diabetes, and 5 patients [18.5%] from atrial fibrillation). The size of the occlusion device was 15.30 ± 6.43 mm. Hospital stay was 6.0 ± 3.5 days.
Twenty-three patients completed the 1-year follow-up period, during which no residual shunting was observed. Four patients were lost after the 1-month follow-up.
Echocardiography results. Table 2 shows the echocardiographic variables at 7 days, 30 days, 90 days, and 1 year after PDA closure. After 7 days, left ventricular end-diastolic diameter was improved (from 6.24 ± 0.84 cm to 6.00 ± 0.83 cm; P<.001). Compared with baseline, there were improvements at 30 days, 90 days, and 1 year in left atrium diameter (from 4.46 ± 0.75 cm to 4.06 ± 0.76 cm to 3.94 ± 0.83 cm to 3.71 ± 0.78 cm; all P≤.001 vs baseline), in left ventricular end-systolic diameter (from 4.69 ± 0.84 cm to 4.24 ± 0.87 cm to 4.06 ± 0.92 cm to 3.87 ± 0.92 cm; all P<.001 vs baseline), and in left ventricular end-diastolic diameter (from 6.24 ± 0.84 cm to 5.69 ± 0.85 cm to 5.53 ± 0.86 cm to 5.34 ± 0.75 cm; all P<.001 vs baseline). Ejection fraction and pulmonary arterial systolic pressure remained unchanged (all P>.05).
When comparing the short-term echocardiographic outcomes (at 30 days) to the long-term outcomes (at 1 year), there was a significant improvement in left ventricular diameter (P<.001), left ventricular end-systolic diameter (P<.001), left ventricular end-diastolic diameter (P<.001), and ejection fraction (P=.02).
Color Doppler echocardiography showed no residual shunting after the procedure. One year after the procedure, 18 patients had mild regurgitation, 3 patients had moderate regurgitation, and 2 patients showed no change. The 2 patients who showed no change continued to have severe regurgitation 1 year after the operation. However, 1 of these patients showed improved New York Heart Association (NYHA) class from III to II despite the fact that ventricular remodeling did not occur, while ejection fraction slightly increased from 38% to 40%. The other patient showed worsening heart function, with an increase in pulmonary arterial pressure from 18 to 40 mm Hg; this patient also had a history of hypertension, diabetes, and atrial fibrillation.
Complications. Surgeries were successful in all patients, without any occlusion. Hemolysis occurred in 2 patients, subcutaneous hematoma in 4 patients, and fever in 2 patients after transcatheter closure of PDA. All complications were non-severe and were managed medically.
Discussion
The management of PDA with severe mitral regurgitation remains a challenge for cardiologists and surgeons. The conventional treatment for this condition is open-heart surgery with PDA ligation and mitral valve replacement under cardiopulmonary bypass. Although surgical PDA ligation has been proven safe and effective, residual leaks do occur due to incomplete closure during ligation, which often requires recanalization.16 In addition, life-long anticoagulation therapy is needed after mitral valve replacement, imposing increased risk of bleeding. Transcatheter closure has been a well-established procedure since the invention of the new Amplatzer duct occluder, which remarkably improved the outcomes of PDA occlusion.8,17 Nevertheless, there is a lack of data about the outcomes in adult PDA patients who have severe mitral regurgitation.
Therefore, the aim of the present study was to evaluate the immediate and 1-year outcomes of transcatheter PDA closure with severe mitral regurgitation in adult patients. The major finding of this study is that PDA complicated with severe mitral regurgitation can be closed effectively using a standard PDA occluder. Our 1-year follow-up results in 23 patients showed the feasibility and effectiveness of the transcatheter device for closing PDA with severe mitral regurgitation. Early complications related to transcatheter PDA closure in our study included hemolysis, hematoma, and fever. These adverse events were manageable and acceptable compared with the benefits.
Organic and functional mitral regurgitation are totally different disease entities regarding their pathophysiology and management.18 Mitral regurgitation following PDA is most probably functional with normal mitral valve leaf. Functional mitral regurgitation can be reduced after effective treatment of the underlying disease in humans and animals.5,13,19 Transcatheter PDA closure can immediately decrease the LV preload by abolishing the left-to-right shunt. The mitral annular area undergoes changes due to sudden reduction in the preload, thus reducing the preexisting LV volume.20,21 Reducing the size of the mitral annulus can greatly improve mitral regurgitation.
Persistent LV systolic dysfunction has been noticed in adult patients despite successful PDA closure,3 which might be associated with sudden reduction in preload and relative increase in afterload due to removal of low-resistance pulmonary circulation, leading to “afterload mismatch.” In our study, however, the postoperative LV systolic dysfunction was significantly improved. Specifically, the severe systolic dysfunction in 2 patients who could not tolerate open-heart surgery was well managed with transcatheter device closure. Baseline LV ejection fraction, extent of LV dilatation, and PDA diastolic gradient, which were all favorable in the patients of this study, can predict the postclosure LV systolic function.22
Study limitations. This study has some limitations. The sample size is small due to the rarity of adult PDA patients with severe mitral regurgitation, which makes it impossible to draw a solid conclusion. The large age range can induce heterogeneity bias and compromise the generalization of our findings. Finally, further assessment with a longer follow-up is needed.
Conclusion
Transcatheter closure can decrease the LV volume and instantaneously reverse flow volume in adult PDA patients with severe mitral regurgitation. This procedure showed good safety profile and efficacy.
References
1. Rao PS. Coil occlusion of patent ductus arteriosus. J Invasive Cardiol. 2001;13:36-38.
2. Krichenko A, Benson LN, Burrows P, Moes CA, McLaughlin P, Freedom RM. Angiographic classification of the isolated, persistently patent ductus arteriosus and implications for percutaneous catheter occlusion. Am J Cardiol. 1989;63:877-880.
3. Jeong YH, Yun TJ, Song JM, et al. Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure. Am Heart J. 2007;154:436-440.
4. Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med. 2005;352:875-883.
5. Schneider DJ. The patent ductus arteriosus in term infants, children, and adults. Semin Perinatol. 2012;36:146-153.
6. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in collaboration with the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:e143-e263.
7. Masura J, Tittel P, Gavora P, Podnar T. Long-term outcome of transcatheter patent ductus arteriosus closure using Amplatzer duct occluders. Am Heart J. 2006;151:755.e7-755.e10.
8. Masura J, Walsh KP, Thanopoulous B, et al. Catheter closure of moderate- to large-sized patent ductus arteriosus using the new Amplatzer duct occluder: immediate and short-term results. J Am Coll Cardiol. 1998;31:878-882.
9. Bilkis AA, Alwi M, Hasri S, et al. The Amplatzer duct occluder: experience in 209 patients. J Am Coll Cardiol. 2001;37:258-261.
10. Faella HJ, Hijazi ZM. Closure of the patent ductus arteriosus with the Amplatzer PDA device: immediate results of the international clinical trial. Catheter Cardiovasc Interv. 2000;51:50-54.
11. Hobo K, Hanayama N, Umezu K, Shimada N, Toyama A, Takazawa A. Adult patent ductus arteriosus: successful surgery with mitral valvuloplasty. Asian Cardiovasc Thorac Ann. 2009;17:302-303.
12. Harley HR, Watkins AG. A case of rheumatic mitral regurgitation and persistent ductus arteriosus. Br Heart J. 1962;24:245-248.
13. Peller OG, Gold JP, Isom OW. Patent ductus arteriosus associated with rheumatic mitral regurgitation in the adult. Am J Cardiol. 1987;60:924-926.
14. Watanabe N, Toyofuku M, Sato T, et al. A case of adult patent ductus arteriosus with congestive heart failure and severe mitral regurgitation. Cardiovasc Interv Ther. 2011;26:278-280.
15. Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr. 2003;16:777-802.
16. Forbes TL, Evans MG. Optimal elective management of patent ductus arteriosus in the older child. J Pediatr Surg. 1996;31:765-767.
17. Thanopoulos BD, Hakim FA, Hiari A, et al. Further experience with transcatheter closure of the patent ductus arteriosus using the Amplatzer duct occluder. J Am Coll Cardiol. 2000;35:1016-1021.
18. De Bonis M, Maisano F, La Canna G, Alfieri O. Treatment and management of mitral regurgitation. Nat Rev Cardiol. 2012;9:133-146.
19. Saunders AB, Gordon SG, Boggess MM, Miller MW. Long-term outcome in dogs with patent ductus arteriosus: 520 cases (1994-2009). J Vet Intern Med. 2014;28:401-410.
20. Galal MO, Amin M, Hussein A, Kouatli A, Al-Ata J, Jamjoom A. Left ventricular dysfunction after closure of large patent ductus arteriosus. Asian Cardiovasc Thorac Ann. 2005;13:24-29.
21. Eerola A, Jokinen E, Boldt T, Pihkala J. The influence of percutaneous closure of patent ductus arteriosus on left ventricular size and function: a prospective study using two- and three-dimensional echocardiography and measurements of serum natriuretic peptides. J Am Coll Cardiol. 2006;47:1060-1066.
22. Kim YH, Choi HJ, Cho Y, Lee SB, Hyun MC. Transient left ventricular dysfunction after percutaneous patent ductus arteriosus closure in children. Korean Circ J. 2008;38:596-600.
___________________________________________
*Joint first authors.
From the Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted August 28, 2014, provisional acceptance given November 11, 2014, final version accepted February 17, 2015.
Address for correspondence: Xianxian Zhao, Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Email: zxxmedsci@163.com
