Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: the PROSPER study.

Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), are implicated in the development of atherosclerosis. The role of anti-inflammatory cytokines, like IL-10, is largely unknown. We investigated the association of four single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene (4259AG, -1082GA, -592CA, and -2849GA), with coronary and cerebrovascular disease in participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. All associations were assessed with Cox proportional hazards models adjusted for sex, age, pravastatin use, and country. Haplotype analysis of the four SNPs showed a significant association between haplotype 4 (containing the -592A variant allele) and risk of coronary events (P = 0.019). Moreover, analysis of separate SNPs found a significant association between -2849AA carriers with incident stroke (HR (95%CI) 1.50 (1.04-2.17), P value = 0.02). Our study suggests that not only proinflammatory processes contribute to atherosclerosis, but that also anti-inflammatory cytokines may play an important role.

A randomized comparison of the effects of aspirin and clopidogrel on thrombotic risk factors and C-reactive protein following myocardial infarction: the CADET trial.

A randomized, double-blind multicenter trial-the Clopidogrel and Aspirin: Determination of the Effects on Thrombogenicity (CADET) trial-was carried out to compare the effects of clopidogrel vs. aspirin on thrombotic variables and C-reactive protein (CRP), over a 6-month period of treatment, in patients with an acute myocardial infarction within the previous 3-7 days, who were not scheduled for major surgery including coronary artery bypass grafting. Patients (n = 184) were randomly allocated to aspirin (75 mg day(-1)) or clopidogrel (75 mg day(-1)). Blood samples were taken at baseline and then at clinic visits at 1, 3 and 6 months. By 1 month, clottable and immunonephelometric fibrinogen, D-dimer, von Willebrand factor, factor VIII and CRP were significantly (P < 0.05) reduced from baseline values in both treatment groups; as well as tissue plasminogen activator antigen in the aspirin group only. At 6 months, there were no differences between treatment groups (P > 0.05) for any of the variables, whether or not potential confounding variables were adjusted for. Similarly, there were no differences between treatments in the difference between baseline and final values for any of the variables. Aspirin and clopidogrel were thus found to have similar effects on thrombotic variables and CRP in this patient population.

The role of myocardial perfusion scanning, heart rate variability and D-dimers in predicting the risk of perioperative cardiac complications after peripheral vascular surgery.

OBJECTIVES: To study the value of a number of proposed prognostic factors in prediction of the risk of perioperative cardiac events after vascular surgery. DESIGN AND METHODS: Two hundred and ninety-seven patients undergoing peripheral vascular surgery were prospectively studied. Patients underwent preoperative 24 h ambulatory electrocardiography, measurement of haemostatic variables, myocardial assessment of perfusion by dipyridamole-thallium scintigraphy and radionuclide ventriculography. The primary endpoint was cardiac death or nonfatal myocardial infarction within 30 days of surgery. A combined endpoint included the primary endpoint plus occurrence of cardiac failure, unstable angina or serious arrhythmias. RESULTS: The primary endpoint occurred in 21 (7%), and the combined endpoint in 41 (14%) of patients. On multivariate analysis, increased age, previous myocardial infarction, aortic surgery, impaired heart rate variability and a positive thallium scan were independent predictors of primary end-points. Preoperative atrial fibrillation and increased fibrin D-dimer were additional predictors of the combined endpoint. Construction of receiver-operator characteristic curves to examine the incremental value of predictive models showed that sensitivity and specificity of clinical data alone for primary endpoints was 71% and 72% respectively, while for the full model (incorporating heart rate variability and thallium data) this rose to 84% and 80% (p=0.0001). CONCLUSIONS: Preliminary screening using clinical data has limited value in risk assessment prior to vascular surgery but preoperative heart rate variability, D-dimers and thallium scanning provide modest incremental predictive value.

Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure.

OBJECTIVE: Myocardial cellular electrophysiology and intracellular Ca2+ regulation are altered in heart failure. The extent of these changes may vary within the layers of the ventricular wall. To examine this, cell size, action potential and intracellular Ca2+ transient characteristics (Fura-2) were measured in single cardiac myocytes from sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricle of rabbits with heart failure. METHODS: Myocytes were isolated from animals with heart failure induced by chronic coronary artery ligation and from sham operated controls. Trans-membrane potential was measured using high resistance microelectrodes electrodes (30 M omega; 2 M KC1). Fura-2 was loaded into cells by incubation with the AM form. Subsequent fluorescence measurements were used to measure intracellular Ca2+ concentration at a range of stimulus frequencies. RESULTS: Resting cell length was significantly greater in the heart failure group; approximately 115% of control values in sub-epicardial and mid-myocardial cells, and approximately 108% in sub-endocardial cells. Using criteria described by previous studies on other mammalian hearts, functional M cells were identified by a higher maximum rate of depolarisation and longer action potential duration at 90% repolarisation (APD90) compared to the two other myocyte sub-types. In the heart failure group, APD90 and Ca2+ transient duration (CaD50) were prolonged in sub-epicardial and M cells but shortened in sub-endocardial myocytes. These changes were significant at lower stimulus frequencies, but the relative effect diminished at higher frequencies (3 Hz). Peak systolic [Ca2+] was reduced in sub-epicardial and M cells but increased in sub-endocardial cells in the heart failure group compared to controls. At higher stimulus frequencies, end diastolic Ca2+ levels were lower in sub-epicardial cells but higher in sub-endocardial myocytes of the heart failure group compared with controls. In general, changes were greater in heart failure animals with more severe in vivo ventricular dysfunction (ejection fraction < or = 44%). CONCLUSIONS: Heart failure was associated with an increased cell size throughout the left ventricle, but the form of the changes in electrophysiology and Ca2+ transient were dependent on the myocyte sub-type. In particular sub-endocardial cells displayed markedly different changes compared to the other myocyte sub-types.

Effect of socioeconomic deprivation on waiting time for cardiac surgery: retrospective cohort study.

OBJECTIVE: To determine whether the priority given to patients referred for cardiac surgery is associated with socioeconomic status. DESIGN: Retrospective study with multivariate logistic regression analysis of the association between deprivation and classification of urgency with allowance for age, sex, and type of operation. Multivariate linear regression analysis was used to determine association between deprivation and waiting time within each category of urgency, with allowance for age, sex, and type of operation. SETTING: NHS waiting lists in Scotland. PARTICIPANTS: 26 642 patients waiting for cardiac surgery, 1 January 1986 to 31 December 1997. MAIN OUTCOME MEASURES: Deprivation as measured by Carstairs deprivation category. Time spent on NHS waiting list. RESULTS: Patients who were most deprived tended to be younger and were more likely to be female. Patients in deprivation categories 6 and 7 (most deprived) waited about three weeks longer for surgery than those in category 1 (mean difference 24 days, 95% confidence interval 15 to 32). Deprived patients had an odds ratio of 0.5 (0.46 to 0.61) for having their operations classified as urgent compared with the least deprived, after allowance for age, sex, and type of operation. When urgent and routine cases were considered separately, there was no significant difference in waiting times between the most and least deprived categories. CONCLUSIONS: Socioeconomically deprived patients are thought to be more likely to develop coronary heart disease but are less likely to be investigated and offered surgery once it has developed. Such patients may be further disadvantaged by having to wait longer for surgery because of being given lower priority.

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

Effects of cyclic adenosine monophosphate (cAMP) on sarcoplasmic reticulum Ca(2+)-loading in failing rabbit and human cardiac trabeculae.

The response of cardiac SR Ca(2+)-loading to cAMP in failing rabbit and human myocardium was examined. Right ventricular (RV) trabeculae were isolated and mounted for isometric tension measurement. They were treated with saponin to permeabilise the sarcolemma but retain SR function, and bathed in a mock intracellular solution including adenosine triphosphate (ATP) and buffered calcium. Caffeine (10 mM) was used to release calcium from the SR. The amplitude of the caffeine-induced contracture was used as a quantitative gauge of the calcium content of the SR. Trabeculae were isolated from rabbits with coronary ligation-induced heart failure (LIG, n = 11), sham operated controls (SH, n = 10), isoprenaline-infused rabbits (ISO, 7 days mini-osmotic pump 100 micrograms/kg.h; n = 7) and saline-infused controls (SAL, n = 7). Failing human RV trabeculae were obtained at the time of cardiac transplantation. Failing rabbit trabeculae demonstrated increased baseline caffeine-induced contractures compared with controls, the response to cAMP was similar in the two groups (LIG 9.3 +/- 2.8 vs SH 10.6 +/- 3.2% Fmax; P = 0.55), There was no difference in the baseline SR Ca(2+)-loading in ISO trabeculae compared with SAL controls but there was a marked difference in the response to cAMP (11.1 +/- 5.4 vs 4.2 +/- 2.1% Fmax, P = 0.02). SR Ca(2+)-loading in failing human RV trabeculae was related to the severity of LV dysfunction (r = 0.59, P = 0.04) and demonstrated a marked cAMP-induced enhancement of caffeine-contracture (20.2 +/- 4.7% increase of Fmax) which was greater in patients with low compared with high ejection fraction. While beta-receptors are known to be down regulated in heart failure these results suggest that the scope for cAMP-mediated enhancement of SR Ca(2+)-loading is maintained.

Sarcoplasmic reticulum Ca2+ loading in rabbits 8 and 15 weeks after coronary artery ligation.

Calcium uptake by cardiac sarcoplasmic reticulum (SR) is reported to be reduced in heart failure in the human and in a number of animal models. However, the majority of studies have examined end-stage heart failure in the human and few animal studies have taken account of the duration and severity of left ventricular dysfunction. In this study we have compared SR Ca2+ loading in a haemodynamically assessed, coronary artery ligation model of heart failure at 8 and 15 weeks after ligation. Trabeculae were isolated from the right ventricle and mounted for isometric tension measurement. They were treated with saponin to permeabilize the sarcolemma but retain SR function and bathed in a mock intracellular solution including adenosine triphosphate (ATP) and buffered Ca2+. Caffeine was used to release Ca2+ from the SR. The amplitude of the caffeine-induced contracture was used as a quantitative gauge of the Ca2+ content of the SR. Eight weeks after ligation, trabeculae demonstrated enhanced SR Ca2+ uptake as manifest by larger caffeine-induced contractures (e.g. 200 nM [Ca2+], 120 s loading - 38.2+/-9.2 versus 67.3+/-10.1% of maximum Ca2+-activated force, FCa, max, P=0.03). At 15 weeks, trabeculae from ligated hearts were not significantly different from controls with SR Ca2+ loading returning to control levels (e.g. 200 nM [Ca2+], 120 s loading - 47.3+/-9.6 versus 30.2+/-12.8% FCa, max, P=0.12). These data suggest that SR Ca2+ loading may increase in the early stages of heart failure and fall back to normal with an increasing duration of left ventricular dysfunction. Increased incidence of spontaneous Ca2+ release observed from the SR at 8 weeks and not at 15 weeks may represent an arrhythmogenic mechanism specific to the early phase of heart failure.

Effects of in vitro and in vivo exposure to doxorubicin (adriamycin) on caffeine-induced Ca2+ release from sarcoplasmic reticulum and contractile protein function in 'chemically-skinned' rabbit ventricular trabeculae.

Doxorubicin is an anthracycline antibiotic that is used widely as a chemotherapeutic agent. However, the usefulness of this agent is limited due to its cardiotoxic effects. The mechanisms associated with this cardiotoxicity remain essentially unknown, despite numerous studies describing a range of structural and functional abnormalities. The purpose of the present study was to determine the in vivo and in vitro effects of doxorubicin exposure on sarcoplasmic reticulum (SR) Ca2+-content and contractile protein function. The Ca2+-content of SR is shown to have a biphasic response to in vivo and in vitro doxorubicin exposure that is time- and dose-dependent. In vitro doxorubicin exposure initially reduces the SR Ca2+-content, but the predominant action to block the SR Ca2+-release channel increases SR Ca2+-content within 60 min. Similar results are observed with in vivo doxorubicin exposure: it leads to Ca2+-overload. These data are consistent with the view that doxorubicin acts in a similar manner to ryanodine and results in cardiomyopathy due to Ca2+-overload.

Role of nitric oxide, cyclic GMP and superoxide in inhibition by adenosine of calcium current in rabbit atrioventricular nodal cells.

OBJECTIVE: To study the intracellular pathways which mediate the inhibitory actions of adenosine on isoprenaline-stimulated calcium current (ICa) in atrioventricular (AV) nodal myocytes. METHODS: The whole-cell patch-clamp technique was used to record ICa from rabbit AV nodal cells, isolated by enzymatic and mechanical dispersion. RESULTS: Isoprenaline, 0.1 microM, increased peak ICa from 0.58 +/- to 1.23 +/- 0.1 nA, and this increase was reversibly inhibited by adenosine, 10 microM (83 +/- 6%), which we have previously shown to be mediated by nitric oxide (NO) production. A membrane-permeable analogue of cyclic GMP, 8-Br-cGMP (300 microM), an inhibitor of cGMP-stimulated phosphodiesterase, prevented the effect of adenosine on ICa-Methylene blue (10 microM), an inhibitor of NO-sensitive guanylyl cyclase and a generator of superoxide (.02-), did not prevent, but increased, the inhibiting action of adenosine (49.5 +/- 6.6%, P < 0.01). Methylene blue (50 microM) caused a reduction of ICa, with further inhibition when combined with adenosine. A .O(2-)-generating system, xanthine oxidase (0.02 U/ml) and purine (2.3 mM), also increased the inhibitory action of adenosine on ICa. Inhibition of ICa by adenosine in the presence of xanthine oxidase was not prevented by 8-Br-cGMP (300 microM) and was not influenced by pre-incubation of cells with a NO synthase inhibitor, L-NAME (0.5 mM). CONCLUSIONS: The inhibitory effect of adenosine on ICa in rabbit AV nodal myocytes can be mediated by two mechanisms--stimulation of cGMP-stimulated phosphodiesterase by NO-induced cGMP, and a mechanism which involves interaction with .O2- production.

Prolonged asystole induced by head up tilt test. Report of four cases and brief review of the prognostic significance and medical management.

Head up tilt is an established test for assessing patients with vasovagal syncope. Prolonged asystole during the test has previously been reported in patients suffering from the malignant form of this syndrome. Little is known about the prognostic significance of this response and there is no consensus about the optimum treatment. Four such patients are reported who were treated pharmacologically. During follow up they remained free from major events and their symptoms were well controlled. Conservative management is the initial method of choice and only if this fails should implantation of a dual chamber permanent pacemaker be considered.

Role of endogenous opioids and catecholamines in vasovagal syncope.

Head-up tilt testing demonstrates vasovagal mechanisms as a cause for syncope, but the pathophysiology underlying this condition remains unclear. The aim of this study was (i) to measure plasma beta-endorphins, adrenocorticotrophic hormone, cortisol, catecholamines, and brain natriuretic peptide during head-up tilt, and (ii) to assess the effect of naloxone infusion during head-up tilt in subjects with reproducible vasovagal syncope. During the assessment of unexplained syncope, 71 subjects underwent a total of 93 tilt tests (60-70 degrees head upwards for 40-45 min or until syncope occurred) during which frequent blood sampling was performed. Subjects with a positive tilt test (n = 56) (mean duration to syncope 23.6 min) showed a larger rise in beta-endorphin levels prior to syncope (baseline 4.7 +/- 2.2 vs syncope onset 6.9 +/- 3.2 pmol.l-1, P = 0.0001) than those with a negative test (n = 37) (baseline 3.9 +/- 3.9 vs end of test 4.9 +/- 2.3 pmol.l-1, P = 0.03). During tilting, adrenocorticotrophic hormone, cortisol, and noradrenaline increased; adrenaline and brain natriuretic peptide remained unchanged; and these responses were similar in positive and negative test groups. Naloxone (2.6 mg.kg-1 i.v. bolus followed by 20 micrograms.kg-1.min-1 infusion), administered in a double-blind fashion during head-up tilt in nine subjects, failed to modify either the time to syncope or the vasodepressor response. Thus, endogenous opioids appear not to be an important trigger for vasovagal syncope, and other pathophysiological mechanisms should be considered.

Coronary haemodynamics in left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. Previous studies have shown that patients with left ventricular hypertrophy develop electrocardiographic changes and left ventricular dysfunction during acute hypotension, and suggest that the lower end of autoregulation may be shifted upwards. AIM: To measure coronary blood flow (velocity) and flow reserve during acute hypotension in patients with left ventricular hypertrophy. PATIENTS: Eight patients with atypical chest pain and seven with hypertensive left ventricular hypertrophy; all with angiographically normal epicardial vessels. SETTING: Tertiary referral centre. METHODS: The physiological range of blood pressure was determined by previous ambulatory monitoring. Left ventricular mass was determined by echocardiography. At cardiac catheterisation, left coronary blood flow velocity was measured using a Judkins style Doppler tipped catheter. During acute hypotension with sodium nitroprusside, coronary blood flow velocity was recorded at rest and during maximal hyperaemia induced by intracoronary injection of adenosine. Quantitative coronary angiography was performed manually. RESULTS: For both groups coronary blood flow velocity remained relatively constant over a range of physiological diastolic blood pressures and showed a steep relation with diastolic blood pressure during maximal hyperaemia with intracoronary adenosine. Absolute coronary blood flow (calculated from quantitative angiographic data), standardised for left ventricular mass, showed reduced flow in the hypertensive group at rest and during maximal vasodilatation. CONCLUSION: The results are consistent with an inadequate blood supply to the hypertrophied heart, but no upward shift of the lower end of the autoregulatory range was observed.

Nitric oxide mediates the anti-adrenergic effect of adenosine on calcium current in isolated rabbit atrioventricular nodal cells.

The aim of this study was to determine if adenosine exerts an anti-adrenergic effect on rabbit isolated atrioventricular (AV) nodal cells and, if so, the dependence of this effect on nitric oxide (NO) production. Inward Ca current, ICa, was measured in AV nodal cells, enzymatically isolated from rabbit hearts. Isoprenaline (0.1 microM) increased ICa from 676 +/-59 to 1102 +/-86 pA (n =25). This isoprenaline-induced increase in ICa(178 +/-15% of control) was abolished in the presence of 10 microM adenosine (ICa100 +/-2% of control, n =9, P <0.05). This effect of adenosine was completely blocked by the A1 receptor antagonist CPDPX (8-cyclopentyl l, 3-dipropylxanthine, 0.1 microM). In cells pre-treated with the NO synthase inhibitor, L-nitro-arginine methyl ester (L-NAME, 1 mM) the isoprenaline-induced increase in ICa(208 +/-39% of control, n=7) was not reduced by the addition of 10 microM adenosine (195 +/-32% of control). Co-incubation of cells in L-NAME with L-arginine (1 mM, the endogenous substrate of NO synthase) restored the adenosine-induced attenuation of ICa. In these cells, isoprenaline increased ICa (157 +/-7% of control, n =6), and, following addition of adenosine (10 microM) ICa was reduced to 107 +/-8% (P <0.05). The NO-releasing agent SIN-1 (3-morpholino-sydnonimine, 100 microM), inhibited ICa augmented by isoprenaline (n=5). It is concluded that adenosine exerts an anti-adrenergic effect on the AV node via A1 receptors to attenuate a catecholamine-stimulated increase in ICa and that this action involves the intracellular production of NO.

Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group.

BACKGROUND: Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS: We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS: Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051). CONCLUSIONS: Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.

Adenosine increases potassium conductance in isolated rabbit atrioventricular nodal myocytes.

OBJECTIVE: To study the actions of adenosine on the electrophysiology of spontaneously active, rod-shaped cells enzymatically isolated from rabbit atrioventricular (AV) node. METHODS: Calcium-tolerant myocytes were isolated from the region of the AV node by enzymatic and mechanical dispersion. They were rod- or spindle-shaped, with spontaneous activity at 35-37 degrees C, and had higher membrane resistances (776 +/- 283 M omega, n = 13), compared to atrial cells (41 +/- 18.2 M omega, n = 7; P < 0.001). Membrane potential, spontaneous action potentials and transmembrane ionic currents were studied using the whole-cell patch-clamp technique, in current-clamp and voltage-clamp mode. RESULTS: Adenosine (0.1-50 microM) slowed or abolished the spontaneous activity, with hyperpolarisation of the membrane potential. Voltage-clamp experiments showed that adenosine induced an inwardly rectifying time-independent current. The adenosine-induced current was shown to be carried by potassium ions by the effect of increasing external potassium, which altered the reversal potential in accordance with the calculated potassium equilibrium potential. The A1 adenosine receptor antagonist, CPDPX (8-cyclopentyl-1,3-dypropylxanthine), reversed the effects of adenosine and an A1 receptor agonist, R-PIA [R(-)N(6)-(2-phenylisopropyl)adenosine] had effects similar to adenosine. Adenosine also caused a small decrease in inward calcium current (ICa) in some AV nodal cells. CONCLUSIONS: These results indicate that adenosine acts at A1 adenosine receptors to suppress spontaneous activity, hyperpolarise membrane potential and induce a time-independent potassium current in AV nodal cells. These actions, combined with reduction in inward calcium current in some cells, may underlie the negative chronotropic and dromotropic actions of adenosine on rabbit AV nodal cells.

Randomised, prospective evaluation of a new pericardial heart valve: outcome after seven years.

Between 2 February 1987 and 20 March 1990, 170 patients were randomly allocated to receive a new pericardial heart valve (the Bioflo) or the Carpentier-Edwards supra-annular porcine bioprosthesis. Eighty-five patients (mean age 61 years, range 38-77) received 93 Bioflo valves, 46 having aortic valve replacement (AVR), 31 mitral valve replacement (MVR) and 8 aortic and mitral valve replacement (A+MVR); 85 patients (mean age 62.1 years, range 41-77) received 99 Carpentier-Edwards porcine valves (48 AVR, 23 MVR and 14 A+MVR). Cumulative follow-up totals 926 patient-years (mean 5.45 +/- 1.93, median 6.03, maximum 7.47 years). The overall operative mortality rate for the Bioflo group was 2.4%, and 5.9% for the Carpentier-Edwards group. At 7 years, there was no statistically significant difference in survival or in any prosthesis-related complication between the pericardial and porcine valve recipients overall, or when the data were analysed according to valve implant position. The actuarial survival rate at 7 years for the Bioflo group was 80.1 +/- 5.1% and 72.3 +/- 5.9% for the Carpentier-Edwards group. Freedom from structural valve deterioration (SVD) at 7 years for Bioflo patients was 98.5 +/- 1.5% and for Carpentier-Edwards patients 91.2 +/- 4.1%. No patient in the Bioflo group has required reoperation for SVD. The randomised prospective trial has proven practical and effective and has shown the pericardial valve to perform at least as well as the porcine valve up to 7 years when all of the standard outcome measures of valve performance are assessed.