Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns.

Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4) were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques.

The clinical risk in heart transplantation: is it evaluable?

At the moment, there is no score to evaluate clinical risk in heart transplantation. There is a need for such an instrument due to the extended criteria for donations and for recipient evaluation for transplantation. We divided the 203 consecutive patients who underwent heart transplantation (HTx). Between January 1999 and December 2007 into two groups: high and low risk based on several common well-defined variables. Donors were also divided into high- and low-risk groups. We matched the four groups to obtain risk cohorts: GA (high risk), GB and GC (intermediate risk) versus GD (low risk). We analyzed the 30 day-mortality showing a significant difference between GD and the other groups (P = .05) in contrast to no significant difference in 1- and 3-year survival rates among GA, GB, GC, and GD. Although the development of a specific score for heart transplantation is desirable and would be useful, a careful, case-by-case evaluation is indispensable.

Validation of limited sampling strategy for estimation of mycophenolic acid exposure during the first year after heart transplantation.

BACKGROUND: Individualization of mycophenolate mofetil (MMF) dosing based on mycophenolic acid (MPA) therapeutic drug monitoring may minimize the risk of organ transplant rejection. The MPA area under the 12-hour concentration-time curve (MPA-AUC(0-12h)) is a more powerful predictor of rejection than are MPA trough levels. Measurement of MPA-AUC(0-12h,) however, is difficult and clinically impractical. The limited sampling strategy (LLS) has been proposed to overcome this problem. OBJECTIVE: To validate the predictive performance of MPA LSS algorithms previously published for heart transplant (HTx) recipients (initial group) when applied to a new independent group of 29 HTx recipients (validation group) during the first year after transplantation. PATIENTS AND METHODS: In a previous study, we established 2 algorithms using a LSS in HTx recipients: (1) 5.568 + 0.902 x C(1.25) + 2.022 x C(2) + 4.594 x C(6) and (2) 3.8 + 1.025 . C(1.25) + 1.819 x C(2) + 1.566 x C(4) + 3.479 x C(6). Agreement between abbreviated AUC and the full AUC(0-12h) was tested using the Bland-Altman method. The validation group was used to test and assess bias and precision. RESULTS: The 2 LSS algorithms used predicted the corresponding MPA-AUC(0-12h) with a mean bias of -4.85% and -3.6% and mean precision of 15.9% and 14%, respectively. CONCLUSIONS: The MPA-AUC(0-12h) obtained using the LSS may be useful to guide clinical management and dosing. This study prospectively validates 2 algorithms for calculation of MPA-AUC(0-12h) using an LSS calculated in HTx recipients. Bias and precision values suggest that our algorithms could be used for MPA therapeutic drug monitoring predictions in HTx recipients who share the same characteristics.

Therapeutic mycophenolic acid monitoring by means of limited sampling strategy in orthotopic heart transplant patients.

Therapeutic drug monitoring (TDM) is essential to maintain the efficacy of many immunosuppressant drugs while minimizing their toxicity. TDM of mycophenolate mofetil requires area under the curve AUC determinations but appears laborious, costly, and clinically impractical. To overcome these problems, limited sampling strategies (LSS) have been proposed in adult and pediatric renal transplant patients. The purpose of this study was to develop an LSS in heart transplant patients. Forty-four mycophenolic acid (MPA) full AUC(0-12h) profiles were generated by high-performance liquid chromatography in nine heart transplant patients during the first 12 weeks posttransplant. Each patient received concomitant cyclosporine and prednisone therapy. Multiple stepwise regression analysis was used to define the time points of MPA levels to explain the MPA AUC(0-12h). Agreement between abbreviated AUC and the full AUC(0-12h) was tested by means of a Bland and Altman analysis. The highest coefficient of determination r(2) among MPA AUC and single concentrations (r(2) = .610) was observed with C(2), while C(12) provided the lowest one (r(2) = .003). Stepwise linear regression showed that the minimal model with the best estimation of MPA AUC(0-12h) was obtained at timed values of 1.25, 2, and 6 hours. The corresponding estimated model was AUC = 5.568 + 0.902 * C(1.25) + 2.022 * C(2) + 4.594 * C(6) (r(2) = .926). Bland and Altman analysis revealed good agreement between predicted AUC and full AUC. A further interesting model equation obtained by four samples was AUC = 3.800 + 1.015 * C(1.25) + 1.819 * C(2) + 1.566 * C(4) + 3.479 * C(6) (r(2) = .948).

Intraoperative transesophageal echo-Doppler evaluation of stentless aortic xenografts. Incidence and significance of moderate gradients.

BACKGROUND: The aim of this study was to assess the utility of intraoperative transesophageal echocardiography (TEE) in the evaluation of patients undergoing aortic valve replacement with the CryoLife-O'Brien (CLOB) Stentless Porcine Aortic Bioprosthesis. METHODS: Between May 1994 and March 1995, 26 patients (15 men, mean age 68.4+/-10.78 years) had a CLOB valve in the aortic position. Transprosthetic gradients and valve regurgitation were detected by intraoperative TEE. Prosthetic regurgitation and transvalvular gradients were evaluated at six-month intervals using transthoracic echo-Doppler (TTE). RESULTS: The majority of implants resulted in low gradients (83.7%), with only four patients exhibiting a moderate gradient (15.3%). Color flow Doppler imaging showed central aortic regurgitation in only four of 25 patients (trivial, n=4; mild, n=1). There was one paravalvular leak (trivial, n=1). At follow-up examination (mean 37+/-12 months), 24 of 25 patients exhibited low mean gradients (7.25+/-2.81 mmHg). At follow-up one patient who had low velocities in the LVOT at perioperative evaluation exibited a moderate gradient (45 mmHg) with an effective orifice area of 0.8-0.9 cm(2). CONCLUSIONS: Intraoperative TEE was effective in assessing prosthetic stentless valve function.

Stentless aortic valve replacement in elderly patients.

OBJECTIVE: Seven-year clinical and hemodynamic results of the Cryolife O'Brien (CLOB) stentless bioprosthesis in elderly patients are reported. METHODS: From 1993 to 2000, 36 patients aged >75 years had a CLOB implanted in the aortic position. Eighteen (50%) were male. All patients were monitored with serial echocardiograms performed preoperatively, at discharge, six months, one year and yearly thereafter. RESULTS: The 30-day mortality was 2.4% (1/36). Actuarial survival at one, five and seven years were 96.7+/-1.5, 94.8+/-2.0 and 94.8+/-2.0%, respectively. Peak and mean gradients (PG and MG) reduced and effective orifice area index (EOAI) increased over time (P<0.001). Left ventricular mass index (LVMI) reduced by 32 g/m2 at discharge (P<0.001) and by 33 g/m2 at six months (P<0.001) without further significant changes. CONCLUSIONS: In our series CLOB xenograft resulted to be a satisfactory valve substitute in elderly patients.

Left ventricular mass regression after aortic valve replacement with CryoLife-O'Brien stentless aortic bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: Left ventricular (LV) hypertrophy has been shown adversely to affect LV function and late outcome after aortic valve replacement (AVR). The study aim was to assess the time course of LV mass regression (LVMR) after AVR with a CryoLife-O'Brien stentless bioprosthesis, and to identify factors affecting late reduction of myocardial hypertrophy. METHODS: In total, 113 patients (60 males, 73 females; mean age 70.9+/-6.5 years) were studied by echocardiography preoperatively, at discharge, at six and 12 months postoperatively, and yearly thereafter. LV diameter and thickness were measured using M-mode echocardiography; LV mass was calculated using the Devereux formula and indexed by body surface area (BSA). RESULTS: LV end-systolic diameter, end-diastolic diameter, septal thickness and wall thickness decreased significantly after surgery (p <0.001). LV mass index (LVMI) was reduced by 16.6, 13.6, 10.1, 3.1, 3.3, 1.7, 2.6, and 1.8% at discharge and at 6 months and 1, 2, 3, 4, 5, and 6 years, respectively. Most LVMR occurred within the first year, with further (not significant) reductions at later examinations. Male sex (p = 0.002), arterial blood pressure > or =150 mmHg (p <0.001), LV ejection fraction (LVEF) < or =35% (p = 0.01), NYHA functional class > or = III (p = 0.01), atrial fibrillation (p <0.001), mean transvalvular gradient > or =40 mmHg (p = 0.001), and prevalent aortic incompetence (p <0.001) were factors influencing LVMR, independently of baseline effective orifice area and prosthesis size. CONCLUSION: AVR with the CryoLife-O'Brien stentless prosthesis resulted in significant LVMR. These findings encourage the use of this bioprosthesis in appropriate patients.

The A-Med right heart support for off-pump coronary artery bypass grafting.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) presents several advantages but, mainly due to the impaired diastolic filling of the right ventricle, the displacement of the heart can cause hemodynamic instability. The aim of this study was to investigate the possible role of the A-Med right heart support during OPCAB. METHODS: We report our early experience with the A-Med system (A-Med, West Sacramento, CA, USA) during OPCAB. The system consists of a coaxial cannula, a microcentrifugal pump and a control console. The coaxial cannula is passed through the right atrium with the tip of the cannula positioned in the main pulmonary artery. Thus the blood is actively removed from the right atrium and returned to the pulmonary artery. RESULTS: We successfully used this right heart support in 2 patients undergoing elective OPCAB. In both cases the system was used during the exposure of the proximal portion of the obtuse marginal branch. A mean pump flow of 3.2 l/min guaranteed normal cardiac output and hemodynamic stability during the exposure of the posterior target area. No complication occurred and the patients were discharged shortly after surgery. CONCLUSIONS: In our early experience the A-Med right heart support was safe and effective and allowed achievement of hemodynamic stability during exposure of the posterior areas of the left ventricle.

Time course of left ventricular remodeling after stentless aortic valve replacement.

BACKGROUND: Stentless aortic valves are associated with a significant decrease in left ventricular hypertrophy. This study examined the time course and factors affecting left ventricular mass regression (LVMR) after aortic valve replacement (AVR) with Cryolife O'Brien (CLOB) (Cryolife International, Atlanta, Ga) stentless valves. METHODS: Between 1993 and 2000, 130 consecutive patients underwent AVR with CLOB. Mean age was 71.3 +/- 6.3 years. Sixty-four (49.2%) were male. Mean body surface area (BSA) was 1.7 +/- 0.2 m(2). Mean valve size implanted was 23.6 +/- 2.0 mm. All patients were monitored with serial echocardiograms; the first study was performed preoperatively, and subsequent controls were at 6 months, 1, 2, 3, 4, 5, 6, and 7 years, respectively. Left ventricular mass was calculated by the Devereux formula and indexed by BSA. RESULTS: Analysis of variance showed a significant reduction in the left ventricular mass index (LVMI) over time (P < .001). Most LVMRs occurred within the first 6 months, and after 1 year LVMI had decreased by 37.5% with further, but not statistically significant, reductions at later examinations. We found that baseline BSA > 1.75 m(2), male sex, arterial blood pressure > or = 150 mm Hg, left ventricular ejection fraction < or = 35%, New York Heart Association functional class > or = III, non-sinus rhythm, and prevalent aortic incompetence to be factors influencing LVMR. LVMR was not related to postoperative effective orifice area < or = 0.85 cm/m(2) and prosthetic size. CONCLUSIONS: AVR with a CLOB valve is followed by a significant LVMR that occurs soon after surgery. It is influenced by several patient-related factors: most of them can be predicted preoperatively.

HBV and HCV infections in heart transplant recipients.

BACKGROUND: Heart transplant (HTx) recipients risk acquiring hepatotropic viral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of these infections on post-HTx survival remains unclear. The aim of the present study was to define the prevalence, clinical features, and natural history of HBV and HCV infections in a cohort of HTx recipients. METHODS: We retrospectively studied 360 consecutive patients who had undergone HTx. Clinical picture, hepatic injury indexes, and HBV/HCV viral serology were followed post-transplant. RESULTS: During follow-up (average, 8 +/- 3.1 years), 49 (16.5%) of the HTx recipients tested positive for at least 1 of the 2 viruses (3.1% HBV, 12% HCV, 0.5% concomitant infection). The prevalence of HCV infection in heart transplant recipients transplanted before and after 1990 was 28% and 4.2%, respectively, the latter being markedly lower (p < 0.001) than in earlier series of HTx recipients and much lower than expected in the age- and sex-matched general population. All HBV-positive and 58% of HCV-positive recipients developed chronic liver disease. Sixteen percent of patients developed cirrhosis during follow-up, and 8% died of end-stage liver disease. CONCLUSIONS: The prevalence of HBV and HCV in a large population of HTx recipients is not very different from that reported in the general population. Active viral replication of HBV and an aggressive natural history of both infections are seen in HTx recipients, however. The low prevalence of HBV- and HCV-related infection in recent series probably reflects current viral screening and vaccination policies.

Early and midterm results of model 300 CryoLife O'Brien stentless porcine aortic bioprosthesis.

BACKGROUND: The Cryolife O'Brien (CLOB) is a composite stentless bioprosthesis constructed from noncoronary leaflets of three porcine aortic valves. This study aimed to investigate early and midterm results after aortic valve replacement with CLOB xenograft. METHODS: Between 1993 and 2000, the CLOB was implanted in 125 patients (62 men; mean age 71.3+/-6.4 years). Mean prosthesis size was 23.6+/-2 mm. Mean follow-up time was 37.0+/-12.1 months. Patients underwent echocardiographic studies preoperatively, at discharge, at 6 and 12 months postoperatively, and yearly thereafter. RESULTS: Early (30-day) mortality rate was 2.4% (3 of 125 patients). Of the four late deaths, none was valve related. Actuarial 7-year survival was 93.6%+/-3%. Seven-year freedom from primary valve failure was 98.1%+/-1.8%. All patients showed an improvement of functional status (p < 0.001). ANOVA revealed a significant reduction over time in peak and mean systolic gradients (p < 0.001). Effective orifice area index increased (p < 0.001) and left ventricular mass index significantly reduced in all valve sizes (p < 0.001) during this time interval. CONCLUSIONS: Because the early and midterm results with CLOB xenograft have been satisfactory, we encourage its use as a valve substitute, particularly in patients with small aortic roots.

Coronary artery bypass grafting in patients with dialysis-dependent renal failure: ten-year results.

BACKGROUND: Coronary artery disease has been reported to be accelerated in patients with chronic renal failure on maintenance dialysis. Coronary artery bypass grafting (CABG) in patients on long-term dialysis is still a debated issue. METHODS: We retrospectively reviewed 19 patients (12 men, 7 women, mean age 64 +/- 11.2 years) with end-stage renal disease who underwent CABG between 1990 and 2000. Operative procedures were CABG alone in 15 (78.9%) patients and CABG associated with valve procedures in 4 (21.1%) patients. RESULTS: The early (30-day) mortality rate was 10.5% (2 of 19 patients). Non-fatal complications occurred in 6 patients (31.5%). Four delayed deaths occurred; the actuarial survivals at 1, 2, 5 and 10 years were 0.86 +/- 0.14, 0.78 +/- 0.10, 0.68 +/- 0.13 and 0.54 +/- 0.15 respectively. Among 13 survivors the mean Canadian Cardiovascular Society class was 1.3 +/- 0.3 (p < 0.001 vs preoperatively). ANOVA procedures showed age (p = 0.01), Canadian Cardiovascular Society class > or = III (p < 0.001), urgent/emergency operation (p < 0.001), left ventricular ejection fraction < 0.50 (p < 0.001), a prior myocardial infarction (p = 0.01), a preoperative mean creatinine level > or = 5 mg/dl (p = 0.02) and a duration of dialysis > or = 60 months (p = 0.03) to be strongly related to early and delayed mortality. CONCLUSIONS: CABG in patients with dialysis-dependent chronic renal failure is associated with acceptable results. Accurate patient selection, early referral to surgery, and adequate perioperative management are advisable.

Aortic repair in Marfan's syndrome: prevention of mechanical leaflets damage.

Aortic incompetence in Marfan's syndrome results from distortion or dilatation of the sinuses of Valsalva, annuloaortic ectasia or a combination of these problems. Valve leaflets in these patients are macroscopically normal in spite of aortic insufficiency. Replacement of the ascending aorta, root and aortic valve with a composite graft was, for a long time, the treatment of choice for Marfan patients. Valve-preserving procedures (remodeling or reimplantation) provide the advantages of avoiding the shortcomings of standard surgical techniques, and maintaining the functional integrity of the left ventricular (LV) outflow tract, aortic root and ascending aorta. We developed a modified valve-sparing reimplantation technique for avoiding leaflet damage. This was achieved by leaving a 'cushion' of aortic wall (8--10 mm) that, sewn on the Dacron graft, works as a 'damper' and prevents leaflets injury during the systolic opening of the valve. For final judgment of this operative method long-term results are necessary.

The CryoLife O'Brien stentless porcine aortic bioprosthesis: 5-year follow-up.

BACKGROUND: Mortality, morbidity, complication rates, and echo hemodynamic results using the Cryolife O'Brien stentless aortic bioprosthesis over a 5-year period are reported. METHODS: The stentless valve was implanted in 97 conscecutive patients, 54 male and 43 female, mean age 70.9 +/- 6.5 years. All patients underwent preoperative, discharge (early study), 6-month (intermediate study), and late (18.3 +/- 10.4 months) echocardiography. RESULTS: The actuarial 5-year survival rate was 93.9% +/- 3%. Aortic regurgitation was absent in 95.5%, mild in 3.4%, and moderate in 1.1%. Peak and mean systolic gradients were significantly lower at discharge (p < 0.001) and at the 6-month follow-up (p < 0.001) but did not significantly fall further at the late study (p = NS). The effective orifice area index at discharge (p < 0.001) and at 6 months (p < 0.001) differed significantly from preoperative values, but variations at late study were not significant (p = NS). Left ventricular mass index decreased early postoperatively (p < 0.001) and at 6-month assessment (p < 0.001) with a further significant reduction at late echocardiography (p = 0.04). CONCLUSIONS: The 5-year results of this stentless valve showed a low rate of valve-related complications with excellent hemodynamic performance in all valve sizes.

Early recovery of left ventricular function after stentless versus stented aortic valve replacement for pure aortic stenosis and severe cardiac dysfunction.

OBJECTIVE: The aim of this study was to evaluate early recovery of systolic function after stentless aortic valve replacement (AVR) versus stented AVR. METHODS: Fifty-four consecutive patients with pure aortic stenosis and impaired left ventricular function (LVEF < or = 35%) were studied retrospectively. Aortic regurgitation, concomitant valvular or coronary artery surgery, atrial fibrillation, and a previous AVR were exclusion criteria. Twenty-two patients (mean age, 70.0 +/- 6.5 years) received a stentless bioprosthesis and 32 (mean age, 58.9 +/- 6.2 years, P =.031 between groups) a mechanical or stented biologic valve. Patients underwent echocardiography preoperatively, at discharge, at 6 months, and at 1 year after surgery. RESULTS: At 6 months, analysis of variance demonstrated significant differences between groups in fractional shortening measured at the endocardium and midwall fractional shortening (<0.001), velocity of circumferential shortening (P <.001) ejection fraction (P =.02), left ventricular mass index (P <.001), systolic meridional wall stress, and circumferential wall stress (P <.001), One-year studies confirmed these findings. CONCLUSION: LV function showed, after a stentless AVR, an early recovery greater than in patients receiving a stented valve.

Open heart surgery in patients with dialysis-dependent renal insufficiency.

OBJECTIVE: Chronic renal failure (CRF) is commonly considered a significant factor for increased morbidity and mortality after cardiac surgery. METHODS: To assess the risk in our population we retrospectively analyzed 28 patients (16 men and 12 women, mean age 58.1+/-10.8 years) with end-stage renal disease (ESRD) undergoing cardiac surgery between 1989 and 2001. Sixteen (57.2%) patients had isolated coronary artery bypass grafting (CABG), nine (32.1%) had isolated valve replacement, and three (10.7%) underwent combined CABG and valve replacement. Preoperatively, 20 (71.4%) patients were on hemodialysis and eight (28.6%) on peritoneal dialysis. Mean preoperative duration of dialysis was 38.7+/-24.9 months (range, 3 to 93 months). RESULTS: There were two perioperative deaths (30-day mortality, 7.1%). Actuarial survival at 1, 2, 5, and 12 years was 0.85+/-0.7, 0.73+/-0.10, 0.65+/-0.12, and 0.54+/-0.14, respectively. Among 22 survivors, mean NYHA class was 1.7+/-0.8 (p < 0.001 vs. preoperatively) and mean CCS class was 1.6+/-0.6 (p < 0.001 vs. preoperatively). CCS/NYHA functional class IV (p = 0.01), urgent/emergency operation (p < 0.001), LVEF < 35% (p < 0.001) were strongly related to early and late mortality. CONCLUSIONS: Open-heart operations can be performed with acceptable short- and long-term results in patients with CRF on dialysis. Adequate preoperative management with identification of high-risk patients and a more aggressive approach before the onset of symptoms of cardiac failure are advisable.

Lymphoproliferative disorders in heart transplant recipients: role of hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection.

Post-transplant lymphoproliferative disorders (PTLD) are a well known complication after orthotopic heart transplantation (OHT). Although Epstein-Barr virus (EBV) infection has long been implicated in the pathogenesis of such disorders, other factors may play a part. Because of its lymphotropic properties, hepatitis C virus (HCV) may induce clonal expansion of B-lymphocytes and lead to PTLD. The aim of this study was to evaluate the potential association between HCV and EBV infection and PTLD in OHT patients. The retrospective study considered 404 adult patients screened for HCV. EBV serology, histology, and molecular analysis on tissue biopsies were performed in the PTLD patients (10/404, 2.5%). HCV positivity was found in 36/404 (8.9%) patients. The EBV genome was expressed on all neoplastic tissue samples analyzed. A higher proportion of HCV-positive patients developed PTLD than the HCV-negative cases (8% vs 2%, P = 0.017). EBV has a demonstrated role in the onset of PTLD, but HCV infection probably has to be considered as well.