Cardiovascular events and treatment of children with high risk medulloblastoma.

BACKGROUND: Children with high-risk medulloblastoma are treated with chemotherapeutic protocols which may affect heart function. We aimed to assesscardiovascular events (CVE) in children with medulloblastoma/primitive neuroectodermal tumors (PNET). METHODS: We retrospectively collected data from a case series of 22 children with high-risk medulloblastoma/PNET admitted to the Santobono-Pausilipon Hospital, Naples, Italy from 2008 to 2016. All patients received the Milan HART protocol for high-risk brain malignancies as first line treatment (induction phase), followed by a consolidation phase with Thiotepa and hematopoietic stem cells transplantation, except for 1 patient who received the Milan HART as second line therapy. Four patients also received second line treatment, while 4 patients also received maintenance therapy. Patients underwent cardiac examination, including ECG, echocardiography and serum biomarkers, before antineoplastic treatment initiation and then when clinically needed. Six patients developed CVE (CVE group); 16 patients had no CVE (NO-CVE group). FINDINGS: In the CVE group, 3 patients presented acute CVE during chemotherapy (2 patients with left ventricular (LV) dysfunction, 1 patient with arterial hypertension), while 3 patients presented chronic CVE after chemotherapy completion (2 patients with LV dysfunction, 1 patient with ectopic atrial tachycardia). After a 51 months median follow-up, 9 patients died: 4 from the CVE group (in 2 cases heart failure-related deaths) and 5 from the NO-CVE group (progression of disease). INTERPRETATION: A relevant percentage of children treated for medulloblastoma/PNET develops CVE. Heart failure potentially due to chemotherapy may represent a cause of death. Hence, in these patients, strict cardiac surveillance is essential. FUNDING: No funding was associated with this study.

New Oral Anticoagulants Versus Warfarin in Atrial Fibrillation After Early Postoperative Period in Patients With Bioprosthetic Aortic Valve.

BACKGROUND: The efficacy of novel nonvitamin K antagonist oral anticoagulants (NOACs) in nonvalvular atrial fibrillation (AF) to prevent stroke is well assessed, but NOACs use in AF that occurs after bioprosthetic aortic valve replacement (AVR) is not endorsed. This retrospective real-world study evaluated the efficacy and safety of NOACs prescribed no earlier than 4 months after AVR as an alternative to warfarin in patients with AF. METHODS: We pooled 1032 patients from the databases of 5 centers. Ischemic/embolic events and major bleeding rates were compared between 340 patients assuming NOACs and 692 prescribed warfarin. Propensity score matching was performed to avoid the bias between groups. RESULTS: The NOACs vs warfarin embolic/ischemic rate was 13.5% (46 of 340) vs 22.7% (157 of 692), respectively, (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.37-0.75; P < .001), and the incidence rate was 3.7% vs 6.9% patients/year, respectively (log-rank test P = .009). The major bleeding rate was 7.3% (25 of 340) vs 13% (90 of 692) (HR, 0.5; 95% CI, 0.33-0.84; P = .007), and the incidence rate was 2% vs 4% patients/year (log-rank test P = .002.) After propensity score matching, the NOACs vs warfarin embolic/ischemic rate was 13.1% (42 of 321) vs 21.8% (70 of 321) (HR, 0.6; 95% CI, 0.4-0.9; P = .02), and the incidence rate was 4.1% vs 6.7% patients/year (log rank test P = .01). The major bleeding rate was 7.8% (25 of /321) vs 13.7% (44 of 321) (HR, 0.5; 95% CI, 0.31-0.86; P = .01), and the incidence rate was 2.4% vs 4.2% patients/year (log-rank P = .01). CONCLUSIONS: In a real-word study, NOACs use overcomes the indications provided by guidelines. This study evidenced that NOACs use in patients who developed AF after bioprosthetic AVR was more effective in prevention of thromboembolism and safe in reduction of major bleeding events compared with warfarin.

Status of coronary disease and results from early endovascular aneurysm repair after preventive percutaneous coronary revascularization.

BACKGROUND: The incidence of coronary artery disease (CAD) is high in patients with an aortic aneurysm but preoperative routine coronary angiography and preventive coronary revascularization are not recommended to reduce cardiac events in patients with severe CAD. AIM: This study evaluated the safeness and efficacy of preventive percutaneous coronary intervention (PCI) in patients with severe CAD scheduled for endovascular aneurysm repair (EVAR). METHODS: All patients with descending thoracic aneurysm (DTA) or abdominal aortic aneurysm (AAA) scheduled for EVAR underwent preliminary coronary angiography. Based on coronary angiography results, 917 patients (40.7%) had significant CAD and were treated by percutaneous coronary intervention (PCI; CAD group) and 1337 patients (59.3%) were without or with mild/moderate CAD and were considered as controls (no-CAD group). To evaluate the safeness and efficacy of preventive PCI in patients with severe CAD undergoing EVAR, groups were compared for hospital and 12-month cardiac adverse events. RESULTS: CAD was present in 1210 patients (53.6%): significant in 917 patients (38%) and mild to moderate in 293 patients (5.3%). Hospital and 12-month cardiac events occurred in 15 (1.6%) and 13 (1.4%) CAD group patients and in 9 (0.7%) and 8 (0.4%) no-CAD group patients (p = .05 and p = .08), respectively. Hospital and 12-month cardiac deaths occurred in 3 (0.3%) and 2 (0.2%) CAD group patients and in 3 (0.2%) and 2 (0.2%) no-CAD group patients (p = .9 and p = .9), respectively. CONCLUSION: The strategy to treat severe CAD preoperatively by PCI and early subsequent EVAR brings a similar outcome to that in patients without or with mild/moderate CAD.

Safety of aortic aneurysm repair 8 weeks after percutaneous coronary intervention for coronary artery disease: a cohort study.

Guidelines advice against dual antiplatelet therapy (DAPT) discontinuation less than 12 months after percutaneous coronary intervention with drug-eluting stents (DES-PCI). However, any delay of necessary surgery in patients with descending thoracic (DTA) or abdominal aortic aneurysm (AAA), treated by DES-PCI, increases the risk of aneurysm rupture/dissection. We evaluated the safety of 8-week waiting time between DES-PCI and endovascular aortic repair (EVAR). 1152 consecutive patients with coronary artery disease (CAD) needing elective DTA or AAA repair were enrolled and divided into two groups. Group A included 830 patients treated by DES-PCI for significant CAD who underwent surgery 8 weeks after implantation. Group B included 322 patients treated by DES-PCI at least 6 months before with no residual significant CAD and treated by elective EVAR. Groups were compared according to a composite of death, myocardial infarction, stent thrombosis, cerebrovascular events and bleeding. No aneurysm rupture/dissection occurred while waiting for surgery. Hospital averse events occurred in 6.2% (52/830) group A patients versus 6.5% (21/322) group B patients (p = 0.8). Mortality was 0.7% (6/830) in group A and 0.9% (3/322) in group B (p = 0.7). Multivariate predictors of events were triple vessel DES-PCI (p < 0.001), > 3 stents implanted (p < 0.001), early-generation stents (p < 0.001), diabetes insulin requiring (p = 0.01), stent diameter < 3.0 mm (p = 0.009) and total stented length > 30 mm (p = 0.02). Eight weeks of waiting after DES-PCI in addition to an adequate management of DAPT were safe in terms of cardiac morbidity and bleeding complications. No aneurysm rupture occurred in the interval before surgery.

Aortic stenosis and aortic regurgitation express different titin isoforms: Differences and relationships with functional and geometric characteristics.

Background-Titin represents an important biomechanical sensor which determines compliance and diastolic/systolic function of the left ventricle (LV). To assess the different titin-isoform expression and the relationships with functional and geometric patterns, we analyzed titin-isoform expression and cardiomyocytes contractile function in myocardial biopsy samples of patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS) and for aortic regurgitation (AR). Method -Specimens, collected from the LV of 35 with AS and 35 with AR undergoing AVR were analyzed for titin-isoform expression and cardiomyocytes force measurement. Ten donor hearts were analyzed as controls for normal values. Results were implemented with preoperative geometry and function assessed by Doppler echocardiography. Results-Compared to controls, N2BA/N2B titin-isoforms ratio was reduced to 0.24 in AS (p < 0.001) but increased to 0.51 in AR (p < 0.001). N2BA/N2B titin-isoforms ratio was further reduced in 8 patients with severe (restrictive) diastolic dysfunction (0.17 ±â€¯0.03, p < 0.001) but was increased in patients with severe systolic dysfunction (0.58 ±â€¯0.07, p < 0.001). As compared to controls, Fpasive was higher in AS (6.7 ±â€¯0.2 vs 4.4 ± 0.4 kN/m2, p < 0.001) but was lower in AR (3.7 ±â€¯0.2 vs 4.4 ±â€¯0.4 kN/m2, p < 0.001). Total force was comparable. Fpassive was significantly higher in AS patients with severe than with moderate LV diastolic dysfunction (7.1 ± 0.5 vs 6.6. ±â€¯0.6, p = 0.004). Conclusions-titin-isoform expression differs in AS and AR as adaptive response to different pathophysiologic scenarios. Co-expressing isoforms at varying ratios results in modulation of the passive mechanical behavior of the LV at different degree of dysfunction and allows for compensative adjustment of the diastolic/systolic properties of the myocardium.

Impact of different values of prosthesis-patient mismatch on outcome in male patients with aortic valve replacement.

AIMS: Mortality and left ventricular mass (LVM) recovery/regression after aortic valve replacement in patients with prosthesis-patient mismatch (PPM) is controversial. This study evaluated the impact of different values of indexed effective orifice area (EOAi) in male patients on mortality and indexed LVM (ILVM) recovery/regression. METHOD: The study recruited 376 male patients with and without PPM after aortic valve replacement with different EOAi cut-off values. RESULTS: At EOAi 0.85 cm/m or less, 295 patients had PPM (78.5%). ILVM recovery occurred in 60.5% of no-PPM patients versus 46.1% of patients with PPM (P = 0.003), and ILVM regression was 35 versus 25% (P < 0.001). Time for ILVM regression was shorter in no-PPM group. At EOAi 0.75 cm/m or less, 201 patients had PPM (53.4%). ILVM recovery occurred in 55.4% of no-PPM patients versus 45.2% of patients with PPM (P = 0.06), regression was 32 versus 29% (P = 0.09). Time for ILVM regression was similar between groups. Regardless the cut-off value for PPM definition, mortality was similar. CONCLUSION: LVM recovery/regression, but not mortality, was different at different EOAi. The cut-off value at EOAi 0.75 cm/m or less guaranteed a more balanced patient distribution between groups and the best compromise between specificity and sensitivity.

Severe prosthesis-patient mismatch after aortic valve replacement for aortic stenosis: Analysis of risk factors for early and long-term mortality.

BACKGROUND: Severe prosthesis-patient mismatch (PPM) is considered to further decrease survival compared to moderate PPM. This study aimed to assess the impact of severe PPM on survival after aortic valve replacement (AVR). METHODS: We retrospectively studied 2404 consecutive patients with PPM who underwent first-time AVR for pure stenosis between January 2003 and December 2014. Mismatch was moderate for indexed effective valve orifice >0.65 to <0.85cm2/m2 and severe for indexed effective valve orifice ≤0.65cm2/m2. Moderate mismatch occurred in 2165 patients (89%), and severe in 239 (11%) patients. Logistic multiple regression with bootstrapping and propensity score analyses were performed using 29 clinical and demographic data to assess the risk-adjusted impact of severe mismatch on mortality. The Cox proportional hazards model was constructed to process the long-term outcome. RESULTS: Early mortality was 2.3% (51/2165) in moderate mismatch group and 3.7% (9/239) in severe mismatch group (p=0.2). Mortality at 5 and 10 years, was 218/1470 (14.8%) and 252/585 (43.1%) for moderate mismatch and 43/198 (21.7%) and 61/105 (58.1%) for severe mismatch (p=0.02 and p=0.006). Multivariable predictors of late mortality were as follows: age ≥70 years, left ventricular ejection fraction ≤40%, indexed left ventricular mass >220g/m2 and concomitant coronary artery revascularization. After propensity score matching, conditional logistic regression analysis demonstrated no relationship between severe mismatch and increased mortality at 5 postoperative years (HR, 0.9; 95% CI, 0.7-1.6; p=0.06), whereas it was significant at 10 postoperative years (HR, 1.9; 95% CI, 1.2-2.5; p=0.03). During the follow-up, severe mismatch was associated with more frequent hospital readmissions for cardiac events (0.12 vs. 0.08 events/patient/year, p=0.007). CONCLUSIONS: Patients with severe mismatch had lower long-term survival and higher incidence of hospital readmissions for cardiac events. However, the effect of severe mismatch on outcome appeared mainly related to the preoperative risk profile of each patient.

Comparison of Left Ventricular Myocardial Structure and Function in Patients with Aortic Stenosis and Those with Pure Aortic Regurgitation.

OBJECTIVE: We aimed to support the structural and functional distinction between aortic stenosis (AS) and aortic regurgitation (AR). METHODS: Biopsy specimens taken from 70 selected patients (35 with AS and 35 with AR) undergoing aortic valve replacement (AVR) were analyzed for their cardiomyocyte dimensions and structure, interstitial fibrosis and contractile function. To determine normal values of contractile function, 10 donor hearts were analyzed. RESULTS: Cardiomyocyte diameter was higher in AS than in AR (22.7 ± 2.2 vs. 13.2 ± 0.7 µm, p < 0.001). Length was higher in AR (121.2 ± 9.4 vs. 95.6 ± 3.7 µm, p < 0.001). Collagen volume fraction was increased in both AS and AR, but was lower in the AS specimens (7.7 ± 2.3 vs. 8.9 ± 2.3, p = 0.01). Myofibril density was reduced in AR (38 ± 4 vs. 48 ± 5%, p < 0.001). Cardiomyocyte diameter and length were closely linked to the relative left ventricular (LV) wall thickness (R2 = 0.85, p < 0.001 and R2 = 0.68, p = 0.003). The cardiomyocytes of AS patients had higher Fpassive (6.6 ± 0.3 vs. 4.6 ± 0.2 kN/m2, p < 0.001), but their total force was comparable. Fpassive was also significantly higher in AS patients with restrictive rather than pseudo-normal LV filling (7.3 ± 0.5 vs. 6.7 ± 0.6, p = 0.004). In AS patients, but not in AR patients, Fpassive showed a significant association with the cardiomyocyte diameter (R2 = 0.88, p < 0.001 vs. R2 = 0.31, p = 0.6). CONCLUSIONS: LV myocardial structure and function differ in AS and AR, allowing for compensative adjustment of the diastolic/systolic properties of the myocardium. © 2015 S. Karger AG, Basel.

Multiple composite grafts (k, π or double-Y) in coronary artery surgery: a choice or a necessity?

OBJECTIVES: Composite grafts allow complete arterial revascularization with minimal aortic manipulations. The Y-T configuration supplies all distal branches adequately, whereas it is unclear whether complex composite configurations (K, Π or double-Y) are equally at rest or when challenged by maximal requirements. METHODS: Forty-seven patients who underwent off-pump coronary artery revascularization by multiple arterial composite grafts (K, Π or double-Y) were retrospectively evaluated. Indication for this surgical option was porcelain aorta or conduit unavailability. Composite systems were evaluated by intraoperative flow measurements and perioperative transthoracic Doppler ultrasonography, 12 months later also by exercise test, sestamibi scintigraphy at rest and during induced hyperaemia and by 64-slice multidetector CT angiography. RESULTS: A total of 141 distal anastomoses were implanted as composite grafts. Perioperative flow measurements and 12-month Doppler ultrasonography were adequate at rest. At stress test, chest pain and/or induced ECG evidence of ischaemia are found in 16 patients (39%). During dipyridamole-induced hyperaemia, single-photon emission computed tomography image revealed that mean summed stress score was 7.2 ± 5.7, summed difference score 5.3 ± 4.2 and coronary flow reserve 1.7 ± 0.2. CONCLUSIONS: Multiple composite grafts, albeit adequate at rest, were unable to meet flow requirements during maximal hyperaemia. In daily practice, their use must be not a choice but rather a necessity in those patients without alternative options.

Y grafts with the left internal mammary artery and radial artery. Mid-term functional and angiographic results. Cohort study.

BACKGROUND: This retrospective cohort study investigated the functional and haemodynamic mid-term results over 3-years follow up of the left internal mammary artery (LIMA) conduit in composite Y-graft configuration with radial artery (RA) in a population of patients who underwent off-pump coronary artery bypass grafting (CABG). METHODS: 148 patients who underwent off-pump CABG with composite Y-graft, were evaluated over 3-year follow up. Two-day dipyridamole induced maximal hyperaemia/rest 99mTc-sestamibi was scheduled preoperatively and 36 months after surgery for functional evaluation. Morphological evaluation was performed by 64 slice multidetector computed tomography (CT) 36 months after surgery. RESULTS: Clinical adverse events were rare within 3 years follow up. Minimal to severe scintigraphic evidence of stress induced ischaemia occurred in 24 patients. Left ventricular (LV) hypertrophy (HR 3.1; 95% CI, 1.5-9.3; p = 0.01) and poor coronary run off (HR 4.1; 95% CI, 2.1-10.8; p = 0.005) were significant multivariate predictors of reversible stress induced ischaemia. 64 slice multidetector CT showed that the main stem of Y composite grafts was patent in all patients, while distal LIMA or RA was stenosed or occluded in 9 patients. CONCLUSION: Composite Y-graft was adequate to meet the flow requirements of target coronary artery either at rest or during maximal hyperaemia. The use of Y-graft should be carefully evaluated in patients with LV hypertrophy and/or poor coronary run-off.

Continuative statin therapy after percutaneous coronary intervention improves outcome in coronary bypass surgery: a propensity score analysis of 2501 patients.

OBJECTIVES: A history of percutaneous coronary intervention increases the risk of death and complications of coronary artery bypass grafting. This retrospective multicenter study evaluated the impact of continuative use of statin on postoperative outcomes when subsequent elective coronary artery bypass grafting is required after percutaneous coronary intervention. METHODS: Among 14,575 patients who underwent isolated first-time coronary artery bypass grafting between January 2000 and December 2010, 2501 who had previous percutaneous coronary intervention with stenting and fulfilled inclusion criteria were enrolled. Continuative statin therapy was used in 1528 patients and not used in 973 patients. Logistic multiple regression and propensity score analyses were used to assess the risk-adjusted impact of statin therapy on in-hospital mortality and major adverse cardiac events. The Cox proportional hazards model was constructed to assess the effect of continuative statin therapy on 24-month outcome. RESULTS: At multivariate analysis, age more than 70 years, 3-vessel or 2-vessel plus left main coronary disease, multivessel percutaneous coronary intervention, ejection fraction 0.40 or less, diabetes mellitus, and logistic European System for Cardiac Operative Risk Evaluation 5 or greater were independent predictors of hospital mortality and major adverse cardiac events. After propensity score matching, conditional logistic regression analysis demonstrated that continuative statin therapy before coronary artery bypass grafting reduced the risk for hospital and 2-year mortality (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.12-0. 57; P=.004 and OR, 0.6; 95% CI, 0.36-0.96; P=.04, respectively) and major adverse cardiac events (OR, 0.31; 95% CI, 0.18-0.78; P=.003 and OR, 0.5; 95% CI, 0.34-0.76; P=.006, respectively). CONCLUSIONS: Long-term statin treatment after percutaneous coronary intervention improves early and midterm outcome when surgical revascularization will be required.

Individualized strategy for clopidogrel suspension in patients undergoing off-pump coronary surgery for acute coronary syndrome: a case-control study.

OBJECTIVE: An increasing number of patients presenting for urgent coronary surgery have been exposed to clopidogrel, which constitutes a risk of bleeding and related events. Based on the wide variability in clopidogrel response and platelet function recovery after cessation, we evaluated the role of point-of-care platelet function testing to define the optimal time for off-pump coronary artery bypass graft (CABG) surgery in a case-control study. METHODS: Three equally matched groups (300 patients in total) undergoing isolated off-pump CABG for acute coronary syndrome were compared. Group A were treated with clopidogrel and prospectively underwent a strategy guided by platelet function testing. Outcomes were compared with 2 propensity score matched groups: group B underwent CABG after the currently recommended 5 days without clopidogrel; group C were never exposed to clopidogrel. RESULTS: Patients in group A had reduced postoperative bleeding compared with those in group B (523±202 mL vs 851±605 mL; P<.001) and a lower number of units packed red blood cells (PRBCs) transfused during the postoperative hospital stay (1.2±1.6 units vs 1.9±1.8 units; P=.004). Postoperative bleeding and the number of units of PRBCs transfused were similar in group A and group C. There was no difference in blood-derived products and platelet consumption, mortality, or the need for reoperation among the groups. Patients in group A waited 3.6±1.7 days for surgery. The strategy used for group A saved 280 days of hospital stay in total. CONCLUSIONS: The strategy guided by platelet function testing for off-pump CABG offers improved guidance for optimal timing of CABG in patients treated with clopidogrel. This strategy significantly reduces postoperative bleeding and blood consumption, and has a shorter waiting time for surgery than current clinical practice.

Doxycycline prevents intimal hyperplasia in vitro and may improve patency of the internal thoracic artery.

OBJECTIVES: The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency. METHODS: Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10⁻5 M and 10⁻6 M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels. RESULTS: At the end of the culture period, neointimal thickness was significantly (P = 0.001) dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases. CONCLUSIONS: Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis.

B-type natriuretic peptide as a biochemical marker of left ventricular diastolic function: assessment in asymptomatic patients 1 year after valve replacement for aortic stenosis.

OBJECTIVES Left ventricular (LV) diastolic dysfunction after aortic valve replacement (AVR) carries a substantial risk of development of heart failure and reduced survival. In addition to echocardiography, B-type natriuretic peptide (BNP) provides a powerful incremental assessment of diastolic function. This study evaluates BNP as a marker of LV diastolic dysfunction in a cohort of patients with preserved LV ejection fraction who underwent AVR for pure aortic stenosis and the relationship between BNP values and the grade of LV diastolic dysfunction. METHODS A total of 113 patients were included in the study. Echocardiographic evaluation was performed preoperatively, 5 days postoperatively and at 12-month follow-up, to assess LV dimensional and functional parameters. Diastolic function was labelled as normal, mild, moderate or severe dysfunction. Concomitantly, BNP levels were evaluated. RESULTS Mild to severe diastolic dysfunction occurred preoperatively in all patients. At 12-month follow-up, 65 (62.5%) patients had mild and 25 (24.1%) moderate to severe diastolic dysfunction. BNP values, categorized for quartile distribution, correlated with diastolic dysfunction grade (P<0.001 for each comparison). At receiver operating characteristic analysis, the BNP level of 120 pg/ml was 91% sensitive and 85% specific for diastolic disease, while 300 pg/ml was 80% sensitive and 91% specific for moderate or severe diastolic dysfunction. Twelve months after AVR, BNP values were strongly correlated with the significant echocardiographic parameters suggestive of diastolic dysfunction (P≤0.006 in all cases). CONCLUSIONS The BNP level following AVR is related to diastolic disease severity and may complement echocardiographic evaluation when symptoms are unclear and LV function is difficult to interpret.

Endothelial nitric oxide synthase expression in postmenopausal women: a sex-specific risk factor in coronary surgery.

BACKGROUND: After coronary artery bypass graft surgery, older women have less favorable clinical outcome and lower conduit patency compared with men. This less favorable outcome can be in part ascribed to impaired endothelium-derived nitric oxide (eNOS) production. This study evaluated endothelial nitric oxide synthase expression in internal mammary artery from postmenopausal women undergoing coronary artery bypass graft surgery. METHODS: Internal mammary artery segments were obtained from 20 postmenopausal woman and 20 matched male patients. Twenty more segments from younger patients were used as controls. Expression of eNOS messenger RNA in internal mammary artery endothelial cells were evaluated by polymerase chain reaction and real-time quantitative reverse transcription polymerase chain reaction. The eNOS protein level was assayed by Western blot. Vascular dynamics of specimens were evaluated by organ chamber methodology. RESULTS: In postmenopausal women, the band of messenger RNA for eNOS was reduced by 37.4% and by 25.2%, respectively, compared with matched men and the control group (62.6%±4.8% versus 74.8%±5.3%, p<0.001). In comparison with the control group lane, the eNOS protein immunoreactive band was 44.2% decreased in postmenopausal women and 34.5% decreased in matched men, and was significantly decreased in postmenopausal women as compared with matched men (55.8%±4.6% versus 65.5%±5.2%, p<0.001). Nitric oxide-mediated vasomotor dynamics were consistent with reduced eNOS production. CONCLUSIONS: Internal mammary artery endothelial cells from women after menopause undergoing coronary surgery have impaired expression of messenger RNA for eNOS and reduced eNOS levels. Reduced bioactivity of nitric oxide translates into impaired endothelial metabolism that could contribute to worse surgical outcome.