Clinical material and methods. Copyright by ICR Publishers 2003

Transcription

1 Fourteen Years Experience with the CarboMedics Valve in Young Adults with Aortic Valve Disease Jan Aagaard 1, Jens Tingleff 2, Per V. Andersen 1, Christel N. Hansen 2 1 Department of Cardio-Thoracic and Vascular Surgery, Odense University Hospital, Odense, 2 Department of Cardio- Thoracic Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Background and aim of the study: Homografts and the Ross procedure are recommended by many surgeons for aortic valve replacement (AVR) in young adults. The study aim was to monitor patient outcome over a 14-year period after implanting mechanical CarboMedics prosthetic heart valves in young adults with aortic valve disease. Methods: Between November 1987 and December 2000, 55 patients (42 males, 13 females; median age 33 years; range years) each received a CarboMedics valve in the aortic position. All patients were included on a consecutive and nonselected basis. Concomitant surgery was performed in five patients. Anticoagulation was commenced on postoperative day 1. After discharge, patients were followed up by their cardiologist or general practitioner using questionnaires and telephone calls. Actuarial estimates of survival and freedom from morbid events were calculated using the Kaplan- Meier method. Results: No patient died during surgery. Complete follow up data were available for all patients; total follow up was 404 patient-years (pt-yr). The 30-day mortality rate was zero. Actuarial survival at 14 years was 90 ± 4.9%, and actuarial freedom from all valverelated events 92 ± 3.7%. No valve thrombosis or major bleeding events were identified. Linearized rates per 100 pt-yr were: embolism 0.25; paravalvular leakage 0.25; prosthetic endocarditis 0.25; and reoperation There was no hemolysis, prosthetic valve dysfunction, or structural deterioration. Conclusion: Over a 14-year period, implantation of the CarboMedics prosthetic heart valve has proven to be an excellent solution for AVR in young adults with aortic valve disease. The Journal of Heart Valve Disease 2003;12:81-86 Autografts and cryopreserved homografts are currently considered as excellent choices for replacement of the diseased aortic valve in young adults (1). Both approaches obviate the need for anticoagulation, have superior hemodynamics and a low incidence of thromboembolism and infection. The requirement for a second aortic valve operation for patients with a homograft or an autograft is expected to increase, as popularity and availability of these valves increases. Since, in terms of durability, mechanical valves are superior to all other types of valve or valve procedure, the present study involved the specific investigation of a young heart valve population, as mechanical valves have been used exclusively in this patient cohort at the authors institution. Here, the authors experience with the CarboMedics prosthetic heart valve implanted in Address for correspondence: Jan Aagaard MD, Department of Cardio-Thoracic and Vascular Surgery, Odense University Hospital, DK-5000 Odense C, Denmark the aortic position over a 14-year period in patients aged 40 years is presented. Clinical material and methods Patients Between November 1987 and December 2000, 55 patients (42 males, 13 females; median age 33 years; range: 15 to 40 years) each received a CarboMedics heart valve prosthesis in the aortic position. All patients were included in the present study on a consecutive and non-selected basis. At the time of surgery, 71% of the patients were in NYHA functional classes III or IV. Hemodynamic evaluation was made using echocardiography and, in selected cases, by angiography. The etiology was native endocarditis in 22% of the patients; in all of these the endocarditis was acute, and the patients were operated as urgent cases. In the other patients, the etiology was calcification and/or degeneration. In total, 24% of the patients underwent urgent surgery, in the majority of cases due to unstable hemodynamics. Copyright by ICR Publishers 2003

2 82 CarboMedics valve in young adults J Heart Valve Dis Table I: Prosthetic valve sizes in 55 young patients undergoing aortic valve replacement with a CarboMedics heart valve prosthesis. Valve size (mm) No. of patients Surgical technique The sizes of valves implanted are detailed in Table I. Five patients (9%) had undergone previous valve surgery (valvuloplasty in four cases, valve replacement in one patient). Concomitant procedures were necessary in five patients. Myomectomy (according to Morrow) was performed in one patient, closure of ventricular septal defect in two patients, and closure of a fistula between a coronary artery and the main pulmonary artery, and between the ascending aorta and the right ventricle each in one patient. The surgical technique was standardized, and included total cardiopulmonary bypass with moderate hypothermia (30-32 C) between 1987 and 1996, and slight hypothermia (36 C) between 1997 and Antegrade, cold crystalloid cardioplegia was used between 1987 and 1994, and combined antegrade and retrograde, cold blood cardioplegia between 1995 and A single aortic cross-clamp was used. Anticoagulation with warfarin was commenced on postoperative day 1. Until 1992, the anticoagulation policy in Denmark was to maintain the International Normalized ratio (INR) at ; however, due to the number of bleeding events that occurred in general, the INR target level was thereafter reduced to Follow up Eight of the patients formed part of a multicenter trial set up by the manufacturer for an FDA application. These patients were followed up on a prospective basis. After discharge from hospital, patients were examined in the outpatient clinic at one and six months, at one year, and thereafter annually over a five-year period. Subsequently, patients were followed up by their general practitioner or cardiologist. Questionnaires were mailed to the general practitioner on an annual basis. The latest follow up was conducted in the spring of 2002, by sending questionnaires to the general practitioner and contacting patients directly by telephone. The other 47 patients were examined in the outpatient clinic at one month after surgery, and followed up thereafter by their cardiologist or local practitioner. A follow up on these patients was conducted in the spring of 2002, again by sending questionnaires to the general practitioner and contacting patients by telephone. In addition, hospital patient databases were checked for all patients. If the collected data provided the slightest impression of a possible valve-related complication, the patient was investigated meticulously. Guidelines for reporting morbidity and mortality as defined by Edmunds et al. (2) were followed throughout the study. Data analysis Actuarial estimates of survival and freedom from morbid events were calculated using the Kaplan-Meier method. Thromboembolic and anticoagulation-related bleeding events were calculated from postoperative day 1. Results Follow up data were available for all 55 patients. The median follow up period was 7.6 years (range: 0.9 to 14.3 years); total cumulative follow up was 404 patient-years (pt-yr). Mortality The actuarial survival rate is shown in Figure 1. Overall survival at 14 years was 90 ± 4.9%. Early mortality There was no operative mortality, and none of the patients died within 30 days of valve replacement. Late mortality In total, four patients died during the follow up period, but in none of the patients was death valve-related. One 32-year-old male committed suicide at one year after surgery, and one 33-year-old male died five years after surgery due to cardiomyopathy. Two patients (a 45-year-old woman and a 45-year-old man) died five years after surgery as a result of myocardial infarction caused by severe coronary atherosclerosis. Valve-related complications The linearized rates of valve-related complications are shown in Table II.

3 J Heart Valve Dis CarboMedics valve in young adults 83 Figure 1: Actuarial survival in 55 young patients after aortic valve replacement with a CarboMedics heart valve prosthesis. Figure 2: Actuarial freedom from all valve-related events in 55 young patients after aortic valve replacement with a CarboMedics heart valve prosthesis. Valve thrombosis No patient experienced thrombosis of the implanted heart valve. Embolism One patient experienced an embolic event at one year after surgery, and this caused a myocardial infarction. However, this patient had been without anticoagulation for six days in connection with minor surgery prior to the embolic event. Anticoagulant-related bleeding No major bleeding events were registered in any patient. Paravalvular leakage One patient with native valve endocarditis developed paravalvular leakage at six months after the primary surgery, and consequently underwent a repeat operation. At surgery, there was no sign of recurrent infection, and the original (23 mm) prosthesis was explanted and replaced with a 25 mm valve. The patient s postoperative recovery was uneventful. Prosthetic valve endocarditis One patient developed a complicating prosthetic endocarditis secondary to a severe postoperative mediastinitis. The patient was reoperated on successfully at two months after the initial surgery. Table II: Complications during follow up * in 55 young patients after aortic valve replacement with a CarboMedics heart valve prosthesis. Complication No. of No. of Linearized patients events rate + Mechanical failure Valve dysfunction Hemolysis Thrombosis Embolism ARB, major events Paravalvular leak PVE Reoperation * Total follow up was 404 patient-years. + Per 100 patient-years. ARB: Anticoagulant-related bleeding; PVE: Prosthetic valve endocarditis.

4 84 CarboMedics valve in young adults Hemolysis, prosthetic valve dysfunction and structural deterioration During the follow up period there have been no reports of either clinically important hemolysis, prosthetic valve dysfunction or structural failure among this group of patients. Reoperation Two patients were reoperated on successfully to alleviate problems that were valve-related. As mentioned earlier, one patient suffered a secondary postoperative prosthetic endocarditis and one suffered a non-infectious paravalvular leakage. All valve-related events Freedom from all valve-related events is shown in Figure 2. Clinical status During follow up, all patients showed an improvement in their functional status, with 34 patients in NYHA class I, and 17 in class II. After convalescence Following postoperative convalescence, all patients resumed their work and normal lifestyle, including sporting activities. None of the patients was disturbed by the valve sound. Discussion Although the main indication for using a mechanical valve rather than either a bioprosthetic valve, the Ross operation or a homograft is related to the superior durability of the mechanical prosthesis, the major concern with these valves remains their thrombogenic potential and the need for postoperative anticoagulation. Currently, the goal is to avoid thrombosis and embolism, and to find a balance between the lowest level of thromboembolic events and bleeding complications. The reported background incidence of spontaneous bleeding in patients aged 64 years and without anticoagulation is approximately 0.8% per year, while for transient plus non-transient cerebral ischemic attacks the rate is approximately 1.3% per year if unselected men aged years are taken into account (3). When operating on young adults, the Ross procedure and homograft valves are considered by many surgeons to be better alternatives to the mechanical valve (4-7). The major difference between the Ross procedure and homograft valves on the one hand, and the mechanical valve on the other hand, is the possibility of anticoagulation-related bleeding occurring with the latter approach. Nevertheless, thromboembolic events, J Heart Valve Dis endocarditis and reoperation are complications that will occur no matter which type of valve or valve procedure is used. Thromboembolic phenomena are rare following the implantation of either autograft or homograft valves (1). With regard to whether the resistance of homografts to recurrent or persistent infection is greater than with mechanical valves, Haydock et al. (8) and McGiffen and colleagues (9) have each reported data from two comparative clinical studies with large patient cohorts. Both groups showed that homografts appear to have a lower immediate risk of recurrent endocarditis than either mechanical valves or xenografts. Haydock et al. (8) reported an overall incidence of recurrent endocarditis of 10% for homografts versus 17% for xenografts or mechanical prostheses, while McGiffin et al. (9) reported incidences of 0% and 17%, respectively. However, these studies were not randomized and were carried out over a 20-year period; hence, differences in outcome may not only be due to the replacement device used but may also reflect differences in patient selection, surgical approach, and perioperative management during the observation period. In a later retrospective study by Niwaya et al. (10), the recurrence rate in patients with prosthetic aortic valve replacement was 12.5% (one of eight patients) versus 3% (two of 60 patients) respectively among patients who received either a homograft or autograft for aortic valve replacement, but again this study was not randomized. In a previous study (11), the recurrence rate of endocarditis was 2% in a group of patients treated for acute endocarditis with radical debridement and implantation of mechanical or stented bioprosthetic devices. The supposed greater resistance of homografts (12) and autografts to recurrent infection is attributed to the content of viable cells in the former with use of a cryopreservation technique. The major concern with autografts and homografts is the need for a second operation within a certain time frame. As Blackstone and Kirklin (13) have pointed out, the risk of a second valve procedures is clearly increased, and therefore every effort should be made to make the first valve procedure long-lasting. The major indication for reoperation after a Ross procedure is either because of an increasing incompetence of the autograft valve, or due to an increasing stenosis of the pulmonary homograft valve. In patients with aortic homograft valves the dominant indication for reoperation is structural valve degeneration resulting in progressive aortic regurgitation. It is expected that about one-third of patients aged <40 years will require reoperation within 12 years after homograft implantation (14). Thus, the issue of homograft or autograft durability is particularly pertinent for the subgroup of younger patients who are expected to live beyond 15

5 J Heart Valve Dis CarboMedics valve in young adults 85 years after operation, and in whom the probability of reoperation will increase (15). In a report by O Brien and colleagues on 1,022 homografts in the aortic position with a median follow up of 7.3 years (7), freedom from reoperation due to structural deterioration for all cryopreserved valves at 15 years was 47% in patients aged 0-20 years, and 85% in patients aged years. The incidence of valve-related reoperations was low both for the autograft and the homograft up to five years (1), but thereafter the deterioration rate increased (especially in homografts), and at 10 years the freedom from reoperation was 88% in the autograft group and 72% in the homograft group. In a homograft study reported by Lund et al. (16), the freedom from reoperation at 10 years was 82%. A mid-term report by Elkins et al. (17) identified a freedom from reoperation after the Ross procedure (autograft and homograft) of 89% at five years, while a 10-year report with a median follow up at 7.7 years of the Ross procedure showed a number of autograft failures during the first five years. Therefore the technique was subsequently changed with narrowing of the aortic annulus (5). During the second five-year period of the study only one patient developed failure of the autograft. In the series reported by Chambers et al. (18), freedom from reoperation for autograft failure was 88% at 10 years and 69% at 25 years. The development of pulmonary homograft stenosis is another cause of late reoperation following the Ross procedure. Ross registry data (19) report a 4% need for revision of the right ventricular outflow tract at five years, and a 16% incidence at 20 years. Among reports on the Ross procedure there is, apart from the patients who have already been reoperated on, a number of cases who are followed closely because of either a slight to moderate autograft insufficiency or a slight to moderate stenosis of the pulmonary homograft. Cryopreserved homografts are unlikely to be available at most centers if a patient is admitted for urgent operation. The Ross procedure is a demanding double procedure which involves the implantation of a homograft, and is not always an option in an urgent situation. In the present study, which involved young valve patients, a mechanical valve was chosen for implantation in the aortic position. The indication for valve surgery was endocarditis in almost one-fourth of the patients, while among the total patient material onefourth required urgent surgery, with the main indication for this being unstable hemodynamics. There was no operative mortality, and the 30-day mortality rate was zero. Although four patients died during the follow up period, the cause of death was not valve-related in any of these cases. Moreover, only two patients were reoperated on - one after two months, and one after six months. In addition, there have not been any late reoperations. In conclusion, the implantation of a CarboMedics heart valve prosthesis in the aortic position of young adult patients indicates that a mechanical valve represents an excellent solution for aortic valve replacement in these cases. References 1. Knott-Craig CJ, Elkins RC, Santagelo KL, McCue C, Lane MM. Aortic valve replacement: Comparison of late survival between autografts and homografts. Ann Thorac Surg 2000;69: Edmunds LH, Jr., Clark RE, Cohn LH, et al. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg 1996;62: Horstkotte D, Schulte H, Bircks W, Strauer B. Unexpected findings concerning thromboembolic complications and anticoagulation after complete10 year follow-up of patients with St. Jude Medical prostheses. J Heart Valve Dis 1993;2: Pessotto R, Wells WJ, Baker CJ, Luna C, Starnes VA. Midterm results of the Ross procedure. Ann Thorac Surg 2001;71:S336-S Oswalt JD, Dewan SJ, Mueller MC, Nelson S. Highlights of a ten-year experience with the Ross procedure. Ann Thorac Surg 2001;71:S332-S Linden PA, Cohn LH. Medium-term follow up of pulmonary autograft aortic valve replacement: Technical advances and echocardiographic follow up. J Heart Valve Dis 2001;10: O Brien MF, Harrocks S, Stafford EG, et al. The homograft aortic valve: A 29-year, 99.3% follow up of 1,022 valve replacements. J Heart Valve Dis 2001;10: Haydock D, Barratt-Boyes B, Macdo T, Kirklin JW. Aortic valve replacement for active infectious endocarditis in 108 patients. J Thorac Cardiovasc Surg 1992;103: McGiffen DC, Galbraith AJ, McLachlan GJ, et al. Aortic valve infection. J Thorac Cardiovasc Surg 1992;104: Niwaya K, Knott-Craig CJ, Santangelo K, Lane MM, Chandrasekaran K, Elkins RC. Advantage of autograft and homograft valve replacement for complex aortic valve endocarditis. Ann Thorac Surg 1999;67: Aagaard J, Andersen PV. Acute endocarditis treated with radical debridement and implantation of mechanical or stented bioprosthetic devices. Ann Thorac Surg 2001;71: Fischlein T, Schütz A, Uhlig A, et al. Integrity and viability of homograft valves. Eur J Cardiothorac Surg 1994;8:

6 86 CarboMedics valve in young adults 13. Blackstone EH, Kirklin JW. Death and other timerelated events after valve replacement. Circulation 1985;72: O Brien MF, McGiffin DC, Stafford EG, et al. Allograft aortic valve replacement: Long-term comparative clinical analysis of the viable cryopreserved and antibiotic 4 degrees C stored valves. J Card Surg 1991;6: McGiffin DC, Galbraith AJ, O Brien MF, et al. An analysis of valve re-replacement after aortic valve replacement with biologic devices. J Thorac Cardiovasc Surg 1997;113: Lund O, Chandrasekaran V, Grocott-Manson R, et J Heart Valve Dis al. Primary aortic valve replacement with allografts over twenty-five years: Valve-related and procedure-related determinants of outcome. J Thorac Cardiovasc Surg 1999;117: Elkins RC, Lane MM, McCue C. Pulmonary autograft reoperation: incidence and management. Ann Thorac Surg 1996;62: Chambers JC, Somerville J, Stone S, Ross DN. Pulmonary autograft procedure for aortic valve disease. Circulation 1997;96: Oury JH, Hiro SP, Maxwell M, Lamberti JJ, Duran CM. The Ross procedure: Current registry results. Ann Thorac Surg 1998;66:S162-S165