Iron deficiency among blood donors: experience from the Danish Blood Donor Study and from the Copenhagen ferritin monitoring scheme.

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.

Clinical outcome of transfusions with extended red blood cell matching in ß-thalassemia patients: A single-center experience.

BACKGROUND: The development of alloantibodies may complicate the management of patients with ß-thalassemia. An extended antigenic matching may reduce the risk of alloimmunization. Our previous study showed that the introduction of molecular red blood cell (RBC) typing allows finding suitable blood units for multi-transfused patients. The aim of this study was to evaluate the benefit of RBC transfusion with extended antigenic match. MATERIALS AND METHODS: At the University of Campania "L. Vanvitelli", we selected ß-thalassemia major patients (age ≤23 years), without preformed alloantibodies. Data of patients receiving transfusion of leukoreduced RBC units for a period of one year with partial better match (PBM) including ABO, RhD, C/c, E/e, K/k antigens and consecutive one year with extended match (EM) including ABO, RhD, C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, S/s antigens, were compared. RESULTS: Eighteen patients, 8 males and 10 females with a mean age of 15.4 years (6.4 SD) received a mean number of 41.2 (6.0 SD) RBC units transfused with PBM and 41.8 (6.2 SD) with EM protocols. After two years of RBC transfusions with both antigen matching protocols, no new alloantibodies were developed in patients. No significant differences in Hb concentration and volume of RBC transfused were found between PBM and EM protocols. CONCLUSIONS: Thalassemia patients may benefit from receiving RBC transfusions based on extended antigen matching as demonstrated by the lack of new alloantibodies. However, our data show a high concordance between PBM and EM protocols considering pre-transfusion Hb, increment of Hb and volume of RBC transfused.

Causes of iron overload in blood donors - a clinical study.

BACKGROUND AND OBJECTIVES: Despite the obligate iron loss from blood donation, some donors present with hyperferritinaemia that can result from a wide range of acute and chronic conditions including hereditary haemochromatosis (HH). The objective of our study was to investigate the causes of hyperferritinaemia in the blood donor population and explore the value of extensive HH mutational analyses. MATERIALS AND METHODS: Forty-nine consecutive donors (f = 6, m = 43) were included prospectively from the Capital Regional Blood Center. Inclusion criteria were a single ferritin value >1000 µg/l or repeated hyperferritinaemia with at least one value >500 µg/l. All donors were questioned about their medical history and underwent a physical examination, biochemical investigations and next-generation sequencing of HH-related genes, including the HFE gene, the haemojuvelin gene (HFE2/HJV), the hepcidin gene (HAMP), the ferroportin 1 gene (SLC40A1) and the transferrin receptor 2 gene (TFR2). RESULTS: Forty of 49 donors were mutation positive with a combined 69 mutations, 54 of which were located in the HFE gene. There were 11 mutations in the TFR2 gene, two mutations in the HFE2 gene and two mutations in the HAMP gene. Only four donors had apparent alternative causes of hyperferritinaemia. CONCLUSION: HH-related mutations were the most frequent cause of hyperferritinaemia in a Danish blood donor population, and it appears that several different HH-genotypes can contribute to hyperferritinaemia. HH screening in blood donors with high ferritin levels could be warranted. HH-related iron overload should not in itself result in donor ineligibility.

Emerging strategies of blood group genotyping for patients with hemoglobinopathies.

Red cell alloimmunization is a serious problem in chronically transfused patients. A number of high-throughput DNA assays have been developed to extend or replace traditional serologic antigen typing. DNA-based typing methods may be easily automated and multiplexed, and provide reliable information on a patient. Molecular genotyping promises to become cheaper, being not dependent on serologic immunoglobulin reagents. Patients with hemoglobinopathies could benefit from receiving extended genomic typing. This could limit post transfusional complications depending on subtle antigenic differences between donors and patients. Patient/donor compatibility extended beyond the phenotype Rh/Kell may allows improved survival of transfused units of red blood cells (RBC) and lead to reduced need for blood transfusion and leading to less iron overload and reduced risk of alloimmunization. Here we discuss the advantages and limitations of current techniques, that detect only predefined genetic variants. In contrast, target enrichment next-generation sequencing (NGS) has been used to detect both known and de novo genetic polymorphisms, including single-nucleotide polymorphisms, indels (insertions/deletions), and structural variations. NGS approaches can be used to develop an extended blood group genotyping assay system.

Characterization of blood donors with high haemoglobin concentration.

BACKGROUND AND OBJECTIVES: The literature contains little on the prevalence and causes of high predonation haemoglobin levels among blood donors. This study aimed to characterize and develop an algorithm to manage would-be donors with polycythaemia. MATERIALS AND METHODS: Between November 2009 and November 2011, we offered haematology consultations to blood donors with repeated haemoglobin concentration (Hb) above the WHO limit for polycythaemia vera (PV) (10·2 and 11·5 mm/16·5 and 18·5 g/dl for women and men, respectively). Investigation of such donors included Hb, haematocrit, mean cell volume, erythropoietin, ferritin, platelet count and leucocyte count, JAK2 V617 and JAK2 exon12 analysis, as well as other routine measurements. RESULTS: Among 46 such donors, 39 had a history of smoking, which contributes to erythrocytosis. Two had PV, five had severe hypertension, one of them because of renal artery stenosis, and two had diabetes mellitus. Thus, we found a high morbidity among such donors. Of the 36 others, 30 donated again before May 2012, at which time the Hb was significantly lower. CONCLUSION: We recommend JAK2 V617 and JAK2 exon12 screening and clinical investigation for donors with concurrently high Hb, high haematocrit and iron deficiency. We also recommend that they stop or cut down on smoking to reduce the risk of thrombosis in general. We disqualified 10 of the donors.

Ethical aspects of blood donors and the recipients of their blood.

To date medical care is inextricable based on blood donors and blood products. The continuing increase and intensification of tests and guidelines also results in a change in deferral and abnormal test results. Donors and recipients of their blood are faced with this information and are confronted with a kaleidoscope of thoughts and emotions. The discussion with respect to paid versus nonpaid donation is not new, but other aspects are less often discussed. We describe these other aspects for donors and recipients of their blood and hope to open the ethical discussion; if and to what extent we should have limits?

Use of statistical process control in the production of blood components.

Introduction of statistical process control in the setting of a small blood centre was tested, both on the regular red blood cell production and specifically to test if a difference was seen in the quality of the platelets produced, when a change was made from a relatively large inexperienced occasional component manufacturing staff to an experienced regular manufacturing staff. Production of blood products is a semi-automated process in which the manual steps may be difficult to control. This study was performed in an ongoing effort to improve the control and optimize the quality of the blood components produced and gives an example of how to meet EU legislative requirements in a small-scale production centre. Data included quality control measurements in 363 units of red blood cells, 79 units of platelets produced by an occasional staff with 11 technologists and 79 units of platelets produced by an experienced staff with four technologists. We applied statistical process control to examine if time series of quality control values were in statistical control. Leucocyte count in red blood cells was out of statistical control. Platelet concentration and volume of the platelets produced by the occasional staff were out of control, which was not the case with the experienced staff. Introduction of control charts to a small blood centre has elucidated the difficulties in controlling the blood production and shown the advantage of using experienced regular component manufacturing staff.

Aberrant expression of the CD8 antigen in B cell chronic lymphocytic leukaemia.

We report a case of aberrant expression of the T cell antigen CD8 in a patient with B cell chronic lymphocytic leukaemia (B-CLL). A 62-year-old Caucasian female with several enlarged lymph nodes and suspected to have B-CLL was referred to our laboratory for routine immunophenotyping. Peripheral blood cell count showed moderate leucocytosis without other abnormalities. The dual-colour flow cytometric analysis showed a typical B-CLL phenotype (CD45+, CD19+, kappa+, lambda-, CD20+, CD23+, IgM+, HLA-DR+, CD5/CD19+, CD3-). In addition, aberrant expression of the T cell marker CD8 was found, present on approximately 64% of the leukemic cells. This is a rare even, the significance and nature of this aberration has not yet been fully determined. In this case, our patient had a rapid response to treatment with a remarkable reduction in the number of leukemic cells only two weeks after beginning treatment.

M-mode echocardiography in aortic stenosis. Clinical correlates and prognostic significance after valve replacement.

To relate preoperative findings at M-mode echocardiography to preoperative clinical and haemodynamic status and to identify possible echocardiographic risk factors for mortality after aortic valve replacement (AVR), 250 patients with AVR for aortic stenosis (AS) were studied. In follow-up averaging 3.2 years there were 22 early (< 30 days) and 23 late deaths. Rising NYHA function class and cardiothoracic index, and left ventricular (LV) failure were related to rising LV end-diastolic and end-systolic diameter index (EDDI, ESDI), and to increasing LV muscle mass index and decreasing fractional shortening (FS). High peak-to-peak systolic aortic valve gradient and LV end-systolic pressure were related to small dimensions of LV with increased FS and posterior wall thickness (PWTh). EDDI < or = 20 mm/m2 and increasing PWTh were independent risk factors for early mortality. Patients with EDDI < or = 20 mm/m2 had normal or supranormal FS. PWTh was the only independent risk factor in long-term survival: 5-year rates being 81 +/- 6%, 94 +/- 3% and 85 +/- 7% for PWTh < or = 13, 14-17 and > or = 18 mm, respectively (p = 0.03). Prevalence of concomitant coronary artery disease (CAD) rose with decreasing PWTh. Angina pectoris in non-CAD patients was related to very high PWTh. Subnormal EDDI was associated with poor surgical outcome, and dilated, poorly contracting LV with congestive heart failure prior to AVR. The degree of LV hypertrophy seemed to be the dominant risk factor, but confounders included myocardial ischaemia due to CAD in low-grade hypertrophy or to hypertrophy per se. A hypothetically confounding factor is the reversibility potential of moderate or severe LV hypertrophy following AVR.

The potential for normal long term survival and morbidity rates after valve replacement for aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The sequelae of early aortic valve replacement (AVR) for aortic stenosis (AS) are controversial, with an increasing body of opinion regarding the patient risk profile as having an influence on long term survival and prosthesis-related morbidity rates. We therefore undertook a comparison of the morbidity and mortality rates of the patients undergoing AVR at our institution over a 22 year period with those in the background population to establish whether early intervention leads to an increased incidence of either. METHODS: A multivariate risk analysis of 630 consecutive patients with AS who were alive 30 days after AVR performed between January 1965 and December 1986 was completed. The patients had a mean age of 59 years (range 14-78 years), 98% received a mechanical prosthetic valve, and 71% were in functional classes III or IV preoperatively. RESULTS: Relative to an age- and sex-matched background population, the patients suffered a slight excess mortality during the first postoperative year, and a significant excess mortality after the 12th year, which was primarily related to congestive heart failure (64% of deaths versus 25% during the first 12 years; p < 0.01). A multivariate Cox regression model allowed calculation of a prognostic index for each patient. The index divided the patients into three groups (from low to high index): group A (n = 195) had normal sex- and age-specific survival, group B (n = 165) had a slight late (> 12th year) excess mortality, while group C (n = 270) had significant excess mortality throughout the follow up. Multivariate risk analysis of thromboembolism (1.7%/pt-yr), anticoagulant related hemorrhage (1.5%/pt-yr), all prosthesis-related complications combined (4.2%/pt-yr), and sudden cardiac events (arrhythmia and myocardial infarct; 1.8%/pt-yr) identified variables underlying advanced preoperative heart disease, coronary artery disease and systemic hypertension as the decisive risk factors. The preoperative prevalence of these risk factors as well as the postoperative incidence of the complications differed significantly between the three patient groups; A < B < C. Incidence rates of stroke in the patients (95% confidence interval) and in sex- and age-matched background populations were: group A, 0.48 (0.13-0.83) and 0.34 %/pt-yr, respectively, group B, 1.07 (0.46-1.68) and 0.52%pt-yr, respectively, and group C, 2.28 (1.50-3.06) and 0.68%/pt-yr respectively. Similar results were obtained for incidence rates of myocardial infarct. CONCLUSION: Operative intervention early in the course of AS, being equivalent to a favorable risk profile, may result in an age- and sex-specific normal long term survival, generally low rates of prosthesis-related complications and a normal incidence of the dominant thromboembolic and hemorrhagic events and of myocardial infarction.

Thirty-day mortality after valve replacement for aortic stenosis over the last 22 years. A multivariate risk stratification.

Over the last 22 years (1965-86), the 30-day mortality rate (30-DMR) after valve replacement for primary or predominant aortic stenosis (AS, N = 690) fell from 20.0% for the first 100 consecutive patients, via 7.8% for the next 490, to 2.0% for the final 100 (P less than 0.0001). There was, however, a wide scatter in 30-DMR in the 11 consecutive 2-year periods, as well as during later years. The variation in 30-DMR was paralleled by changes in a high risk prognostic index (derived from a logistic regression model) and in a high coronary artery disease (CAD) score. In patients with a high CAD score who died within 30 days, 93% (N = 25) had CAD at autopsy compared with 37% (N = 11) of those with a low CAD score (P less than 0.0001). In 205 patients evaluated by coronary arteriography, the 30-DMR was 4.1% in 122 without CAD, 3.6% (3.8% for triple vessel/left main stem) for 55 with CAD who underwent bypass grafting, and 17.9% for 28 with CAD who did not have bypass grafting (P less than 0.0001). Left ventricular failure (LVF; episodes of pulmonary oedema and/or stasis), age, pronounced hypertrophy/strain in the ECG, and a high CAD score were independent incremental risk factors for 30-DMR. Quantitatively, LVF increased the risk 10 times more than pronounced hypertrophy/strain and a high CAD score. LVF also neutralized the influence of age. Modifying (symptom-masking) digitalis and/or diuretic treatment in functional class II patients (N = 189) increased the 30-DMR from 0.9% to 9.1% (P less than 0.01). The scatter of operative year-specific 30-DMR was related to changes in preoperative prognostic patient profiles and to unrevascularized CAD. Operative intervention in AS patients, even with discrete symptoms, and consistent revascularization of significant CAD, should be strongly advocated.

Valve replacement for calcified aortic stenosis in septuagenarians infers normal life-length.

Aortic valve replacement because of pure or predominant stenosis was performed in 1970-1986 on 101 patients aged 70-78 years, including 80 in NYHA function class III or IV. There were 16 deaths within 30 days, and coronary artery disease (unbypassed in all but 1 case) was found in 11 of the 13 with autopsy or preoperative arteriography. None of the 12 patients without significant coronary artery disease at angiography died perioperatively,but one of 12 with combined valve replacement and coronary artery bypass grafting died. Cumulative 1-year survival among the 101 patients/the 85 survivors of the first 30 days and/a normal population matched for sex, age and year of operation was 75/90/96%. Corresponding percentages for 5 years were 64/75/77, for 10 years 43/52/52, and for 15 years 35/42/27. Advanced disease with kidney failure or left ventricular end-diastolic pressure greater than 20 mmHg independently increased the overall mortality rate. The linearized rat of cerebral events (haemorrhage, embolism) was 2.7/100 patient years (age-specific background rate 1.6-1.9/100 patient years). The 30-day mortality among septuagenarians was reduced to 3% in 1988-1989 by routine revascularization in significant coronary artery disease. The patients who survived the first 30 days had normal life expectancy. Early operation may further improve the results.

Twenty-two-year experience with aortic valve replacement. Starr-Edwards ball valves versus disc valves.

From 1965 through 1986, 817 patients underwent aortic valve replacement at our institution. Six hundred forty-five patients received Starr-Edwards ball valves, including 286 Silastic ball valves (Models 1200/1260), 165 cloth-covered caged-ball prostheses (Models 2300/2310/2320), and 194 track-valve prostheses (Model 2400). In contrast, 172 patients received disc-valve prostheses, including 126 St. Jude Medical aortic bi-leaflet disc valves, 32 Lillehei-Kaster pivoting disc valves, and 14 Björk-Shiley valves (6 convexoconcave and 8 monostrut). With respect to preoperative data, the 2 groups were comparable, with the following differences. The Starr-Edwards group included 1) more men (77% versus 51%; p < 0.0001); 2) a significantly older patient population (59 +/- 10 years versus 56 +/- 15 years; p < 0.0001); 3) more patients in New York Heart Association functional class III or IV (72% versus 65%; p < 0.01); 4) fewer patients with angina pectoris as a limiting symptom (20% versus 36%; p < 0.0001); and 5) patients who tended to receive larger prostheses (26 +/- 2 mm versus 23 +/- 3 mm, p < 0.0001). The overall 10-year survival rate +/- standard error was 59% +/- 2% for patients receiving Starr-Edwards valves and 63% +/- 6% for those with disc valves. The linearized complication rates (expressed as percentage per patient-year +/- standard error) for the Starr-Edwards and disc-valve groups, respectively, were 2.0% +/- 0.2% and 1.4% +/- 0.5% for thromboembolism, 2.1% +/- 0.2% and 3.9% +/- 0.8% for Coumadin-related hemorrhage, 0.5% +/- 0.1% and 0.3% +/- 0.2% for endocarditis, 0.3% +/- 0.1% and 0.7% +/- 0.3% for other prosthesis-related complications, and 4.8% +/- 0.1% and 6.4% +/- 1.0% for all complications together. There were no instances of thrombotic occlusion or mechanical failure. After the 6th postoperative year, no thromboembolic events were encountered in patients with a Silastic ball valve; the 15-year freedom from thromboembolic events was 89%. Cox regression analysis showed that 1) a prosthetic orifice diameter of 15 mm or less was associated with an increased mortality; 2) disc valves entailed an increased rate of hemorrhage and prosthesis-related complications considered as a whole; 3) and Lillehei-Kaster valves led to an increased rate of prosthesis-related complications other than thromboembolism, hemorrhage, and endocarditis. Neither the type of prosthesis nor the size influenced the rate of thromboembolism, endocarditis, or prosthesis replacement. Because of their proven durability and relatively low price, we advocate the continued use of Starr-Edwards Model 1260 Silastic ball valves that have an orifice diameter of 16 mm or more.

[Prosthesis-endocarditis in the aortic position in a 22-year case load. Surgical versus conservative treatment]. / Protese-endocarditis i aortaposition i et 22 års materiale. Kirurgisk kontra konservativ behandling.

During the period 1965-1986, a total of 852 patients underwent isolated aortic valve replacement. With 4,875 patients-years at risk, 24 patients developed prosthetic valve endocarditis (PE; 0.49% per patient-year). The five, ten and fifteen year cumulative freedoms from PE were 98.2%, 95.4% and 93.0%, respectively. PE was unrelated to pre- or intraoperative data. No patients submitted to operation for acute/subacute bacterial endocarditis of the native aortic valve developed PE. Out of the 12 episodes of PE within two years of the operation, seven (58%) were caused by Staphylococcus albus compared with two out of 12 (17%; p less than 0.05) subsequent episodes of PE. Seven of the nine infections with Staphylococcus albus were caused by a highly resistant nosocomial variant. Ten of the PE patients underwent replacement of the prosthesis while 14 were treated conservatively. The two therapeutic groups were comparable, although the surgically treated patients tended to be younger and to have more impaired cardiac status. All surgically treated patients and all patients treated conservatively and in whom post mortem verification was possible had paravalvular defects, annular abscesses and/or vegetations on the prosthesis. The thirty-day, one year and ten year cumulative survivals were 80%, 80% and 50%, respectively, after replacement of the prosthesis and 64%, 21% and 7%, respectively, after conservative treatment (p = 0.02). A Cox regression analysis identified conservative treatment, infection with Escherichia coli or Haemophilus influenzae and the need to intensify digitalis/diuretic treatment for congestive heart failure as independent risk factors. It is concluded that replacement of the prosthesis early in the course of the disease should be considered as the treatment of choice.

Valve replacement for aortic regurgitation: earlier operation may reduce the rate of late complications related to the prostheses.

Predictability of prosthesis- and sudden heart-related complications was examined in 121 patients who were alive 30 days after valve replacement (1965-86) for aortic regurgitation. A variety of prosthetic valves, mainly mechanical, were used. The Cox regression model was used to identify independent risk factors and to estimate the predicted freedom of events relative to combinations of these risk factors. In the following, linearized event-rates (LER) are given as number of events per 100 patient years +/- standard error. No risk factors could be identified for endocarditis (LER: 0.3 +/- 0.2) or anticoagulant-related hemorrhage (LER: 1.7 +/- 0.6). Only factors underlying deranged preoperative patient and heart status and cardioplegic method, but not the type of prosthetic valve, had predictive influence on the other complications. Predicted 10-year event-freedoms for low- versus high-risk estimate were 98% versus 46% for thromboembolism (LER: 2.1 +/- 0.6), 87% versus 68% for all prosthesis-related complications (LER: 5.0 +/- 0.8), 100% versus 0% for sudden heart-related events (LER: 2.0 +/- 0.5; myocardial infarction and arrhythmia), and 72% versus 38% for combined prosthesis- and sudden heart-related morbidity and mortality (LER: 7.0 +/- 1.0). By deciding to operate early in the course of aortic regurgitation, the rate of these complications may be "actively" reduced, and longevity and life quality of the patients improved.

Long-term prosthesis-related and sudden cardiac-related complications after valve replacement for aortic stenosis.

Predictability of prosthesis-related and sudden cardiac-related complications was examined in 630 patients who were alive 30 days after valve replacement (1965 to 1986) for aortic stenosis. Follow-up totaled 4,072 patient-years. A variety of prosthetic valves, mainly mechanical, were used. The Cox regression model was used to identify independent risk factors and to estimate predicted event-freedoms relative to combinations of these risk factors. There were no risk factors for endocarditis (0.5 +/- 0.1 [number of events per 100 patient-years +/- the standard error]). Except for "other" prosthesis-related complications (0.4 +/- 0.1), adversely influenced by porcine bioprostheses (n = 15) and by the Lillehei-Kaster prosthesis (n = 25), only factors underlying diseased preoperative patient/cardiac status had predictive influence. Predicted 10-year event-freedoms for low-risk versus high-risk estimate were 86% versus 73% for thromboembolism (1.7 +/- 0.2), 95% versus 32% for anticoagulant-related hemorrhage (2.4 +/- 0.2), 69% versus 36% for all prosthesis-related complications (5.0 +/- 0.4), 93% versus 0% for sudden cardiac-related events (myocardial infarction and arrhythmia) (1.8 +/- 0.2), and 66% versus 0.5% for combined prosthesis-related and sudden cardiac-related morbidity and mortality (6.8 +/- 0.4). In 193 patients with coronary arteriography, coronary artery disease was a significant risk factor for each of the complication modalities examined except other prosthesis-related complications, prosthesis replacement, and endocarditis. Deciding to operate early in the course of aortic stenosis might "actively" reduce the rate of these complications.

The influence of coronary artery disease and bypass grafting on early and late survival after valve replacement for aortic stenosis.

The influence of coronary artery disease and bypass grafting on survival after valve replacement for aortic stenosis (1975 to 1986, N = 512) was analyzed. Mean follow-up for 30-day survivors was 5.1 years (0.1 to 12.9 years). A total of 205 patients had coronary angiography performed: 122 did not have coronary artery disease, 55 with coronary artery disease underwent bypass grafting, and 28 with coronary artery disease did not. Early mortality rates (less than or equal to 30 days)/5-year cumulative survivals (standard error) were 4.1%/86% (4%), 3.6%/68% (8%), and 17.9%/51% (13%), respectively (p less than 0.05/p less than 0.01). Triple vessel/left main stem disease was more prevalent in patients with coronary disease who underwent bypass grafting (47%) than in those who did not (14%; p less than 0.05). Multivariate analysis revealed that right ventricular failure and omission of bypass grafting in patients with coronary artery disease were independent determinants of early mortality. A Cox regression analysis identified coronary artery disease and aortic valve gradient as determinants of mortality after hospital dismissal, which was not influenced by bypass grafting. On the basis of a coronary artery disease score (positive predictive value for coronary artery disease of 66%) developed on the patients with angiography, 307 patients without angiography were divided into 234 with a low score and 73 with a high score. Early mortality rates/5-year survivals (standard error) were 6.4%/86% (2%) and 16.4%/67% (6%), respectively (p less than 0.01/p less than 0.001). Autopsy revealed stenotic or occlusive coronary artery disease in 92% of 12 early deaths in the group with a high coronary artery disease score and in 33% of 15 in the group with a low score (p less than 0.01). Left ventricular failure and a high coronary artery disease score were independent determinants of early mortality, whereas cardiothoracic index, a high coronary artery disease score, and left ventricular failure were independent predictors of death after hospital dismissal. Despite more severe coronary artery disease, bypass grafting reduced early mortality to a level comparable with that of patients without coronary artery disease, contrasting with a high early mortality rate for unbypassed coronary artery disease. Coronary artery disease increased the late mortality rate, which was not modified by bypass grafting. In the group without angiography, undiagnosed and unbypassed coronary artery disease probably increased both early and late mortality. Coronary angiography should be performed in all adult patients with aortic stenosis, and those with significant coronary artery disease should undergo bypass grafting concomitant with valve replacement.