Asian Cardiovasc Thorac Ann 2007;15:476-481
© 2007 Asia Publishing EXchange Ltd
Prosthetic Valve Replacement in Adolescents with Rheumatic Heart Disease
Raja P Akhtar, FRCS,
Abdul R Abid, MBBS1,
Hasnain Zafar, MBBS,
Saqib S Sheikh, FCPS1,
Masud A Cheema, FRCS,
Jawad S Khan, FRCS
Department of Cardiac Surgery
1 Department of Cardiology, Punjab Institute of Cardiology, Lahore, Pakistan
For reprint information contact: Raja P Akhtar, FRCS Tel: 92 30 0846 5515 Fax: 92 42 920 0028 email: rajapakhtar{at}gmail.com, Punjab Institute of Cardiology, Ghaus-ul-Azam Road, Lahore, Pakistan.
 |
ABSTRACT
|
|---|
To assess long-term survival and anticoagulant-related complications after mechanical valve replacement in adolescents with rheumatic heart disease, 88 patients aged 
18 years were prospectively followed up for 10 years (404.2 patient-years). There were 58 (65.9%) boys and 30 (34.1%) girls, with a mean age of 15.4 ± 2.1 years. Mitral regurgitation was detected in 39 (44.3%) patients, and both mitral and aortic regurgitation in 15 (17%). Ball valves were inserted in 52 (59.1%) patients, bileaflet valves in 31 (35.2%), and single-disc valves in 5 (5.7%). There were 4 (4.5%) hospital deaths and 11 late deaths. Patient survival at 30 days, 3 months, 1, 5, and 10 years was 95.5%, 93.2%, 87.5%, 82.9%, and 82.9%, respectively. Mechanical valve thrombosis occurred in 4 patients; it was fatal in 3 of them. Three patients died from stroke. Severe hemorrhage required hospital admission in 4 (4.5%) patients. Mechanical valve replacement in adolescents, with careful follow-up and anticoagulation, has acceptable long-term results.
|
INTRODUCTION
|
|---|
Rheumatic heart disease is endemic in Pakistan, with a prevalence of 5.7 per 1,000.1 A high proportion of patients with rheumatic heart disease are 20 years old.1 The reasons for high incidences of rheumatic fever in Asian countries might be the climate, poor socioeconomic conditions and overcrowding, purulent streptococcal infections, and lack of access to proper medical facilities.1,2 Heart valves affected by rheumatic fever deteriorate rapidly due to recurrences that lead to severe debilitating disease and early death.3 Some cases may be suitable for percutaneous transvenous mitral commissurotomy or repair.3 This, along with strict prophylaxis, buys some time in patients who present early, but most require valve replacement.3 Prosthetic valve replacement in children carries many unique challenges including the small sizes of the left atrium, left ventricle, and valve annulus.4,5 In the long term, there are problems with anticoagulation, subsequent reoperations due to patient-prosthesis mismatch, and reoperation for other native valves due to recurrence of the rheumatic process.4,6 The aim of this study was to assess long-term survival and anticoagulation-related complications in adolescents with rheumatic heart disease requiring mechanical valve replacement.
|
PATIENTS AND METHODS
|
|---|
Between February 1996 and June 2006, prospective follow-up with clinical assessment, international normalized ratio (INR) measurement, and echocardiography was carried out in 88 consecutive adolescents (aged 18 years) undergoing mechanical heart valve replacement for rheumatic heart disease, by the same surgeon. Follow-up ranged from 0.16 to 10.08 years (mean, 3.28 ± 2.68 years; median, 2.75 years), with a total follow-up of 404.2 patient-years. The patients were divided into 3 age groups: group 1 were aged 12 years, group 2 were 13–15-years old, and group 3 were aged 16–18 years. Demographic details and diagnoses are given in Table 1
. The mitral valve was most frequently affected. Two patients had undergone a closed mitral commissurotomy at 4 and 5 years prior to valve replacement. One patient underwent surgery 1 month after percutaneous transvenous mitral commissurotomy. Most patients (92%) were in New York Heart Association functional classes III and IV, and 45 (51.1%) were in atrial fibrillation (AF). Severe pulmonary hypertension, with pulmonary artery pressure > 60 mm Hg, was present in 37 (42%) patients.
Cardiopulmonary bypass was established using a membrane oxygenator and moderate systemic hypothermia. Myocardial preservation was with St. Thomas’ Hospital solution until 1997; thereafter, blood cardioplegia was used, repeated every 20–25 min. The types of mechanical valves implanted were Starr-Edwards, St. Jude Medical, Carbomedics, and Sorin. Until December 2003, we used a Starr-Edwards ball valve as it was the least expensive available. Since then, only bileaflet valves have been used due to considerable reductions in price. Mitral valve replacement (MVR) was performed via standard left atrial exposure, using semi-continuous 3/4 Prolene sutures; a transseptal approach was used in 2 patients as it provided better exposure of the mitral valve. The posterior mitral leaflet was preserved in 31 of 43 patients undergoing MVR; 10 also required tricuspid valve repair. Aortic valve replacement (AVR) was carried out using an oblique aortotomy and interrupted pledgetted Ethicon Ethibond Excel 2/0 sutures (Johnson & Johnson, Piscataway, New Jersey, USA). In 7 of 15 patients undergoing double-valve replacement (DVR), after excising the aortic valve, the mitral valve was excised with preservation of the posterior mitral leaflet. Postoperatively, all patients were moved to the intensive care unit (ICU). After removal of chest drains on the 1st postoperative day, 5,000 units of unfractionated heparin (Heparin Sodium Injection USP, Pharmacia & Upjohn Company, Kalamazoo, Michigan, USA) was injected subcutaneously 8 hourly, and oral warfarin therapy (COUMADIN® DuPont Ethical Pharmaceuticals, Massachusetts,USA) was commenced. Heparin was continued until the INR was > 2. Patients were maintained at an INR of 2.5–3.5. All patients were assessed by 2D and color Doppler echocardiography (Toshiba 6000 Power Vision; Toshiba Medical Systems, Otawarashi, Tochigi-ken, Japan) preoperatively, postoperatively in the ICU, and prior to discharge. At discharge, they were counseled on oral anticoagulation and rheumatic prophylaxis. Follow-up echocardiography was performed at 3 months and then yearly unless otherwise indicated. Anticoagulation was monitored by checking the prothrombin time and INR; if required, patients were admitted until the optimum INR was achieved, and followed up weekly until proper control of INR was assured. Anticoagulation was managed according to the American College of Cardiology guidelines, updated from time to time during the study period.7
The primary endpoint was mortality (early and late). Early mortality was death within 30 days postoperatively or during the same hospital admission. The secondary endpoints were early and late complications. Early complications included pericardial effusion sufficient to cause hemodynamic compromise requiring pericardiocentesis, and wound infection during hospital stay. Late complications comprised anticoagulant-related events, such as valve thrombosis, central nervous system complications, and bleeding. Valve thrombosis was defined as any thrombus in the absence of infection, attached to or near a valve, which partly occluded blood flow or interfered with valve function.8 Valve thrombosis was confirmed by 2D and color Doppler echocardiography. Central nervous system complications included stroke (a new temporary or permanent neurological event) or a focal or global neurological deficit lasting more than 3 weeks or causing the death of the patient.8 A transient ischemic attack was defined as a fully reversible neurological event that lasted less than 24 hours.8 A bleeding event was any episode of major or external bleeding that caused death, hospitalization, or permanent injury (e.g. vision loss), or required blood transfusion.8 Females of child bearing age who conceived were followed up until completion of the pregnancy. During the early years of the study, they were given 5,000 IU of subcutaneous heparin 6–8 hourly in the 1st 12 weeks, followed by oral warfarin therapy until last 15 days of pregnancy, when they were admitted and switched to heparin therapy. Warfarin was restarted 24 hours after delivery at the pre-delivery dosage, along with heparin until INR > 2. This practice has changed, and warfarin is currently continued until 36 weeks when the patient is admitted and switched to intravenous heparin to maintain an activated partial thromboplastin time > twice the control level.
The data were analyzed using Statistical Package for Social Sciences version 14.0 for Windows (SPSS, Inc., Chicago, IL, USA). Categorical variables are expressed as percentages, and continuous variables are given as mean ± standard deviation. Actuarial survival was examined by the Kaplan-Meier method. Events were defined as death and valve-related complications. Linearized event rates were calculated by dividing the total number of events by the patient-years of follow-up.
|
RESULTS
|
|---|
A ball valve was used most often, followed by bileaflet and single-disc valves; operative variables are give in Table 2. There were 4 (4.5%) hospital deaths and 11 late deaths (Table 3); the details are given in Table 4. Of the 88 patients, 84 (95.5%) survived the operation and were discharged from the hospital, 82 (93.2%) were alive after 3 months, and 77 (87.5%) after 1 year (cumulative mortality, 13.5%). At the end of 5 years, survival was 82.9%, and at 10 years, overall survival was unchanged. Only 6 patients were lost to follow-up. Cumulative mortality after 10 years of follow-up was 17.1% (Figure 1). Early complications comprised pseudomonas chest infection in 1 patient, reexploration for bleeding in 3, and pericardial effusion in 2 on the 6th and 7th postoperative day, requiring drainage by pigtail catheter. Valve thrombosis occurred in 4 patients (linearized rate, 0.98% per patient-year). There were 3 fatal mechanical valve thromboses in patients who had undergone MVR with a ball valve (Table 3). One of these was a patient in AF who was 28 weeks pregnant and had stopped taking oral warfarin after MVR. Two patients who had MVR with a ball valve (1 in AF, 1 in sinus rhythm) died in local hospitals after presenting with valve thrombosis; both had a sub-therapeutic INR (< 1.5) and erratic follow-up with self medication. The 4th patient was in sinus rhythm after MVR with a bileaflet valve, and presented in cardiogenic shock secondary to valve thrombosis. She underwent successful thrombolysis with 1.5 million units of streptokinase (STREPTASE® Aventis Behring GmbH, Marburg, Germany). Prior to this event, her anticoagulation was managed at a different hospital and her INR was persistently below 2.0. One year later, she had a subdural hematoma for which craniotomy was carried out with a good recovery; her INR at that time was 4.0. Three patients died postoperatively due to stroke. One patient in AF after MVR developed left hemiplegia 60 months postoperatively. At the time of this event, her INR was 2.2. She made a full recovery. Two patients on irregular medication (INR, 1.5 and 1.3) and in AF after MVR and DVR, suffered a transient ischemic attack at 48 and 67 months postoperatively. One of these underwent AVR and repeat tricuspid valve repair 82 months after MVR; the mitral valve prosthesis was normal. Six patients reported minor dizzy spells. They had normal brain computed tomography scans and echocardiograms. Aspirin 75 mg was added, and they are symptom free. All had an INR in the therapeutic range. Severe hemorrhage occurred in 4 patients (linearized rate, 0.98% per patient-year), requiring admission to hospital. One patient died from intracerebral bleeding, another had a subdural hematoma, as mentioned earlier. The 3rd patient had an abortion secondary to excessive per vaginal bleeding. The 4th patient had gastric erosions. One patient experienced hemarthrosis of the knee joint. Minor bleeding episodes including epistaxis occurred in 6 (6.8%) patients. One nasal bleed required nasal packing. Four patients had one pregnancies each; 2 were uneventful and resulted in the birth of normal babies by spontaneous vaginal delivery. The 3rd patient died from a thrombosed valve, and the 4th was the case of abortion due to vaginal bleeding. All pregnant patients were managed according to the standard protocol, except the one who had valve thrombosis. She switched from oral anticoagulant to intermittent heparin at a lower dose, against medical advice.
View larger version (7K):
[in this window]
[in a new window]
|
Figure 1. Cumulative survival (Kaplan-Meier curve) of 88 adolescents after mechanical heart valve replacement.
|
|
|
DISCUSSION
|
|---|
Rheumatic fever leads to a rapid deterioration and severe deformation of affected valves, rendering them unsuitable for percutaneous intervention or surgical repair.3 Despite every effort to repair the native valves, it is often technically impossible due to grossly diseased and calcified valves.9 Even if a good repair is possible, the ongoing rheumatic process results in early repair failure and redo surgery.9 Homografts have excellent hemodynamics, do not require anticoagulation, and are resistant to thrombosis; but there are problems with availability, limited durability, technical difficultly of insertion, and the results are not reproducible by all.3,10 Bioprostheses in children and adolescents have been largely abandoned due to accelerated degeneration.10 Yu and colleagues11 have shown that bioprostheses have satisfactory results in rheumatic heart disease, but their study population was older. In the younger age group, there is a significant risk of structural valve deterioration, reported to range from 71% to 87% at 10 years.12,13
Our hospital mortality of 4.5% compares well with previous studies where a range of 3.2% to 14% was reported.4,5,12–16 Tiete and colleagues10 had an early mortality rate of 3.7% and a 10-year survival rate of 92% after left-sided mechanical heart valve replacement in children < 16 years of age. Most patients in their study had congenital valve disease, 16 had MVR and 2 had DVR; all with St. Jude valves. Our 10-year survival rate was lower (82.9%) and we encountered more bleeding and anticoagulant-related complications. This might be due to the different patient profile; all of our patients had rheumatic disease, more had AVR, our sample size was larger, and most patients suffering fatal events had erratic follow-up with sub-therapeutic anticoagulation. Ruel and colleagues12 studied 500 patients aged 18–50 years and reported 3.2% early mortality and 10-year survival of rates of 88.3% after AVR and 79.5% after MVR. They found that preoperative AF, left atrial diameter, functional class, and the need for concomitant coronary artery bypass grafting were independent risk factors for late death after MVR. In our study, 10/15 deaths were in patients in AF preoperatively, with class IV symptoms and increased left atrial size.
In a study by Kojori and colleagues4 of MVR in patients < 19-years old (83% congenital, 13% rheumatic, 4% other diseases), the mortality rate was 19% after 15 years. Complications included late arrhythmias (14%), endocarditis (5%), valve thrombosis (3%), bleeding (5%), and permanent pacemaker implantation (5%). In our study, arrhythmias occurred in 2 patients leading to death, while none had permanent pacemaker implantation. Our study differed in that all patients had rheumatic heart disease. John and colleagues3 reported 9.2% 30-day mortality and a 10-year survival rate of 85.6% in patients with rheumatic heart disease (73% < 40 years old; 14.3% < 20 years old) undergoing DVR. Thromboembolism occurred in 35/456 (7.7%) patients, but only 1 died of valve thrombosis, 2 died of major hemorrhage, and nonfatal bleeding occurred in 3. Prosthetic valve endocarditis occurred in 10 (2%) patients. They identified associated pulmonary hypertension as a strong predictor of both morbidity and mortality, with operative mortality of 38.1% in those with pulmonary artery pressures > 60 mm Hg.3 In our study, 37 (42%) patients had pulmonary artery pressures > 60 mm Hg, but we did not observe a significant association between pulmonary hypertension and morbidity or mortality. Long and colleagues13 from China reported 4.8% early mortality, mostly due to serious low output syndrome, while late deaths (3.8%) were due to endocarditis, heart failure, and severe arrhythmia.
The most notable limitation in our study was the use of ball valves until 2003 because of financial constraints. Ball valves are associated with a greater incidence of thromboembolism, and hence more morbidity compared to disc valves. Nevertheless, our experience with the Starr-Edward prosthesis has been good, with only 3 valve-related events among 52 Starr-Edwards valves implanted as aortic and mitral prostheses. Another limitation is that this was a single-surgeon and single-center study. However, this is a first such study in Pakistan, and we hope to enroll other surgeons and centers shortly.
Mechanical valve prostheses have excellent long-term performance but also the drawback of requiring lifelong anticoagulation. The valve pathology in our patients < 18 years was due to rheumatic fever, and not congenital, because of the prevalence of rheumatic fever in this part of the world. When valve conservation is not possible, mechanical heart valve replacement in adolescents has an acceptable long-term prognosis. The inherent complications of anticoagulation with mechanical valves do influence the outcome; however, with proper anticoagulation and follow-up, the complications can be minimized.
|
ACKNOWLEDGMENTS
|
|---|
The authors deeply acknowledge the Residents of the Cardiac Surgery Department, Punjab Institute of Cardiology Lahore, Mrs. Shumaila Afshan, office secretary, Mr. M Raza Qadeer, Librarian, Shaukat Khanum Cancer Research Hospital, and Dr. Farah Khandwala and Miss Alliya Akhtar for their help in completion of this article.
|
REFERENCES
|
|---|
- Rizvi SF, Khan MA, Kundi A, Marsh DR, Samad A, Pasha O. Status of rheumatic heart disease in rural Pakistan. Heart 2004;90;394–9.[Abstract/Free Full Text]
- Agarwal BL. Rheumatic heart disease unabated in developing countries. Lancet 1981;2(8252):910–1.[Medline]
- John S, Ravikumar E, John CN, Bashi VV. 25-year experience with 456 combined mitral and aortic valve replacement for rheumatic heart disease. Ann Thorac Surg 2000;69:1167–72.[Abstract/Free Full Text]
- Kojori F, Chen R, Caldarone CA, Merklinger SL, Azakie A, Williams WG, et al. Outcomes of mitral valve replacement in children: a competing-risks analysis. J Thorac Cardiovasc Surg 2004;128:703–9.[Abstract/Free Full Text]
- Alexiou C, Galogavrou M, Chen Q, McDonald A, Salmon AP, Keeton BK, et al. Mitral valve replacement with mechanical prostheses in children: improved operative risk and survival. Eur J Cardiothorac Surg 2001;20:105–13.[Abstract/Free Full Text]
- Erez E, Kanter KR, Isom E, Williams WH, Tam VK. Mitral valve replacement in children. J Heart Valve Dis 2003;12:25–9.[Medline]
- American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease); Society of Cardiovascular Anesthesiologists, Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing Committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 2006;48;e1–148.[Free Full Text]
- Edmunds LH Jr, Clark RE, Cohn LH, Grunkemeier GL, Miller DC, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations. The American Association for Thoracic Surgery, Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity. Ann Thorac Surg 1996;62:932–5.[Abstract/Free Full Text]
- Talwar S, Rajesh MR, Subramanian A, Saxena A, Kumar AS. Mitral valve repair in children with rheumatic heart disease. J Thorac Cardiovasc Surg 2005;129:875–9.[Abstract/Free Full Text]
- Tiete AR, Sachweh JS, Groetzner J, Gulbins H, Muehler EG, Messmer BJ, et al. Systemic mechanical heart valve replacement in children under 16 years of age. Clin Res Cardiol 2006;95:281–8.[Medline]
- Yu HY, Ho YL, Chu SH, Chen YS, Wang SS, Lin FY. Long-term evaluation of Carpentier-Edwards porcine bioprosthesis for rheumatic heart disease. J Thorac Cardiovasc Surg 2003;126:80–9.[Abstract/Free Full Text]
- Ruel M, Kulik A, Lam BK, Rubens FD, Hendry PJ, Masters RG, et al. Long-term outcomes of valve replacement with modern prostheses in young adults. Eur J Cardiothorac Surg 2005;27:425–33.[Abstract/Free Full Text]
- Long CZ, Zhou XM, Hu JG, Yin BL, Yang YF, Liu F, Yng JF. Prosthetic valve replacement in pediatric patients: analysis of 105 cases. Zhoghua Yi Xue Za Zhi 2005;85:1849–52.
- Shanmugam G, MacArthur K, Pollock J. Mechanical aortic valve replacement: long-term outcomes in children. J Heart Valve Dis 2005;14:166–71.[Medline]
- Shanmugam G, MacArthur K, Pollock J. Pediatric mitral valve replacement: incremental risk factors impacting survival and reintervention. J Heart Valve Dis 2005;14:158–65.[Medline]
- John S, Ravikumar E, Jairaj PS, Chowdhury U, Krishnaswami S. Valve replacement in the young patient with rheumatic heart disease. Review of a twenty-year experience. J Thorac Cardiovasc Surg 1990;99:631–8.[Abstract]
TOP
ABSTRACT
INTRODUCTION
