Circulation Journal Vol.76, February 2012

Circulation JournalOfficial Journal of the Japanese Circulation Societyhttp://www.j-circ.or.jp

ortic stenosis is an age-related disorder that is charac-terized by calcification of the aortic valve, local lipid accumulation, inflammation, and neo-angiogenesis.1

Because the aged population is increasing, increased numbers of patients are experiencing aortic stenosis, so the number of patients requiring aortic valve replacement (AVR) is increas-ing.2 AVR still remains the standard therapy for symptomatic severe aortic stenosis, although transcatheter aortic valve implantation is considered as an alternative therapy for elderly patients at high risk for perioperative complications.3 In Asian countries in particular, female and elderly patients with aortic valve stenosis often have a small aortic annulus.

Prosthesis-patient mismatch (PPM) is the difference bet-ween the area of the implanted prosthetic valve and that of the patients native valve without a stenotic lesion. Previous stud-ies have shown that PPM, defined as an effective orifice area index (EOAI ie, effective orifice area divided by body surface area (BSA))

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University. All patients had previously granted permission for use of their medical records for research purposes.

OperativeTechniquesAortic valve surgery was performed via standard median ster-notomy. Cardiopulmonary bypass was initiated after cannula-tion of the ascending aorta, superior vena cava, and inferior vena cava. A left ventricular vent was inserted via the right upper pulmonary vein. Antegrade/retrograde cold blood car-dioplegia was administered intermittently to maintain cardiac arrest. Moderate hypothermia was applied. After complete excision of the diseased aortic valve, the diameter of the aortic annulus was measured with sizers (St. Jude Medical) for selec-tion of the appropriate prosthesis. The 17-mm St. Jude Medi-cal Regent prosthesis was implanted in the intra-annular posi-tion with the use of 2-0 polyester everting mattress sutures in 65 patients, 2-0 interrupted braided polyester sutures in 12 patients, and in the supra-annular aortic position in 1 patient. Warfarin sodium was started on the day of surgery and con-tinued thereafter so that the international normalized ratio of prothrombin time was maintained in accordance with Ameri-can College of Cardiology/American Heart Association guide-lines. Operative data are shown in Table1.

EchocardiographyStandard M-mode dimensions were obtained according to the American Society of Echocardiography criteria. The mean of 3 measures from 2 different cardiac cycles was taken. The

following variables were obtained: end-diastolic septal thick-ness, left ventricular end-diastolic dimension, and end-dia-stolic left ventricular posterior wall thickness. All Doppler measurements were averaged from more than 3 cycles in patients with sinus rhythm and more than 5 cycles in those with atrial fibrillation. Maximum pressure gradients were cal-culated from the complete Bernoulli equation. Left ventricular mass was calculated according to the Devereux formula.7 The EOA was determined by the standard continuity equation and indexed to BSA.

Follow-upFollow-up transthoracic echocardiographic data were ob-tained for 35 (45%) of the 78 patients at 13.310.8 (mean SD) months after surgery. The clinical status of each patient was evaluated by means of direct hospital visits and telephone in-terviews. Follow-up was 100% complete. Mean follow-up was 32.619.6 months (range, 570 months). A major adverse valve-related event was defined according to the guidelines for reporting after cardiac valve interventions.8

StatisticalAnalysisData are reported as mean SD. Preoperative and postopera-tive echocardiographic data for all patients were compared and analyzed by paired Students t-test. Patients were divided into 2 groups: with and those without PPM at discharge. Dif-ferences between the groups were analyzed by chi-square test or unpaired Students t-test as appropriate. Logistic regression was used to identify factors associated with in-hospital death. Variables were entered into multivariate analysis if univari-ate analysis yielded a P-value

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367Mid-Term Outcomes With 17-mm Regent for AVR

age, preoperative NYHA class III or IV, hypertension, dia-betes, and a concomitant procedure were associated with a major adverse valve-related cardiac event. Multivariate analy-sis showed diabetes to be the only independent predictor of a major adverse valve-related cardiac event (Table3). Freedom from reoperation was 100%. Long-term survival and freedom from cardiac death are shown in Figure2. Of the 76 survivors, 9 (12%) died during the follow-up period: malignancy (n=2), heart failure (n=1), pneumonia (n=1), renal failure (n=1), and unknown (n=4). Actuarial 1-year, 3-year, and 5-year survival rate were 94.8%, 86.3%, and 78.7%, respectively. Univariate analysis identified age, diabetes, renal insufficiency, ejection fraction 1.5mg/dl.HR,hazardratio;CI,confidenceinterval.

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368 OKAMURA H et al.

EchocardiographicVariablesPreoperative echocardiography yielded a mean aortic valve area index of 0.410.13 cm2/m2, a mean left ventricular-aortic pressure gradient (LVAo-PG) of 59.021.5 mmHg, and a mean left ventricular mass index (LVMI) of 17553 g/m2. Follow-up echocardiography revealed a significant decrease in mean LVAo-PG (16.66.8 mmHg), a significant decrease in LVMI (11632 g/m2), and a significant increase in mean

EOAI (0.970.21 cm2/m2). There was no significant difference between the preoperative and postoperative ejection fractions (0.600.14 vs. 0.630.07).

EffectofPPMonLong-TermSurvivalandEchocardiographicVariablesThe EOA was obtained at discharge for 58 (74%) of 78 patients. Of these 58 patients, 18 (31%) had PPM with an

Figure2. Long-term postoperativesurvival and freedom from cardiacdeath.

Figure3. Follow-upechocardiograph-icvariablesofpatientswith(n=18)andwithout(n=40)prosthesis-patientmis-match(PPM)atdischarge.Follow-upvalue in comparison to preoperativevalue.LVAo-PG, leftventricular-aorticpressuregradient;LVMI,leftventricu-larmassindex.

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369Mid-Term Outcomes With 17-mm Regent for AVR

EOAI

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370 OKAMURA H et al.

prosthesis.20,21 These findings suggest that implantation of a 17-mm Regent valve provides not only excellent operative results but also good survival, associated with the better hemo-dynamic results. Minardi et al reported satisfactory hemody-namic performance in 19 patients with the 17-mm Regent valve under dobutamine stress as well as at rest.22

Garatti et al also showed good early and long-term out-comes after AVR with a 17-mm mechanical valve, although their evaluation included only the 17-mm Sorin Bicarbon Slim prosthesis (Sorin Biomedica, Saluggia, Italy), and the 17-mm St. Jude Medical Hemodynamic Plus (St. Jude Medical).23 It must be noted that the follow-up periods were relatively short and the number of patients in each study was small. So, we need to look more carefully into the safety and effectiveness of the 17-mm valve in a large number of patients.

The drawback of a mechanical valve is lifelong anticoagu-lation, and close monitoring is required to prevent postopera-tive complications, including thromboembolism and antico-agulation-related bleeding. Some could argue that mechanical valves (vs. bioprostheses) will increase mortality and morbid-ity as a result of anticoagulation.24 However, in our series, we encountered cerebral hemorrhage in 2 patients, accounting for a linearized rate of 0.5% per patient-year, but no cerebral infarction. These complication rates are comparable to those of patients given a bioprosthesis. Aupart et al studied clinical outcomes of AVR in 1,133 patients who received a biopros-thesis and reported a bleeding complication rate of 0.3% per patient-year and thromboembolism rate of 0.6% per patient-year.25 Despite the need for lifelong anticoagulation in patients who receive a mechanical prosthesis, some reports have indi-cated no significant differences in postoperative quality of life, survival, or incidence of complications between mechanical and biological valves.26

The effect of PPM on prognosis and cardiac function remains controversial. Mohty et al indicated that PPM nega-tively influences long-term survival in specific patient groups such as those with low cardiac function or severe PPM.27 Moon et al reported that PPM had a negative impact on long-term survival only for patients 70 years of age or less.28 Vicchio et al showed that in patients over age 70, severe or moderate PPM did not influence long-term outcome, left ven-tricular mass regression or quality of life.29 In our series, there was no difference in survival or reduction in LVMI between patients with and without PPM, although the incidence of severe PPM was low. Also, our study included only a small number of patients with low cardiac function or severe PPM.

Another mechanical valve currently available for a small aortic annulus is the 16-mm ATS-Advanced Performance valve (ATS Medical, Inc, Minneapolis, MN, USA). Kobayashi et al reported on 15 patients in whom the 16-mm valve was implanted.30 There was no in-hospital mortality or significant postoperative reduction of LVMI despite a high incidence of PPM. However, some of their patients given the 16-mm valve showed no improvement in left ventricular diastolic function at mid-term follow-up.

StudyLimitationsThe limitations of our study should be taken into consider-ation. The main limitation is the relatively low echocardio-graphic follow-up rate. Most of our patients were followed up at another hospital or clinic, some of which were far from the hospital where the operation was performed. In addition, the study group comprised mostly elderly patients. Nearly half of the patients were unable to return for echocardiographic assessment. Whether or to what degree this low follow-up rate

affected our survival and LVMI regression data is unknown. Furthermore, the low incidence of severe PPM in our series might have obscured the potential affect of PPM on out-comes.

ConclusionsIn summary, the 17-mm Regent prosthesis produced satisfac-tory results in terms of survival, physical capacity, and hemo-dynamic performance. Thus, the 17-mm prosthesis could be a reasonable alternative, especially in patients with a small aor-tic annulus. Although we confirmed the safety and effective-ness of the prosthesis over 33 months of follow-up, we need to evaluate outcomes over a longer period and in a substan-tially large study group.

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