Deckers, J.W.

Incomplete segregation of MYH11 variants with thoracic aortic aneurysms and dissections and patent ductus arteriosus (Article)

2013-05-01T00:00:00Z

Thoracic aortic aneurysms and dissections (TAAD) is a serious condition with high morbidity and mortality. It is estimated that 20% of non-syndromic TAAD cases are inherited in an autosomal-dominant pattern with variable expression and reduced penetrance. Mutations in myosin heavy chain 11 (MYH11), one of several identified TAAD genes, were shown to simultaneously cause TAAD and patent ductus arteriosus (PDA). We identified two large Dutch families with TAAD/PDA and detected two different novel heterozygote MYH11 variants in the probands. These variants, a heterozygote missense variant and a heterozygote in-frame deletion, were predicted to have damaging effects on protein structure and function. However, these novel alterations did not segregate with the TAAD/PDA in 3 out of 11 cases in family TAAD01 and in 2 out of 6 cases of family TAAD02. No mutation was detected in other known TAAD genes. Thus, it is expected that within these families other genetic factors contribute to the disease either by themselves or by interacting with the MYH11 variants. Such an oligogenic model for TAAD would explain the variable onset and progression of the disorder and its reduced penetrance in general. We conclude that in familial TAAD/PDA with an MYH11 variant in the index case caution should be exercised upon counseling family members. Specialized surveillance should still be offered to the non-carriers to prevent catastrophic aortic dissections or ruptures. Furthermore, our study underscores that segregation analysis remains very important in clinical genetics. Prediction programs and mutation evaluation algorithms need to be interpreted with caution.

Microsimulation for Clinical Decision-Making in Individual Patients With Established Coronary Artery Disease (Article)

2012-11-29T00:00:00Z

Background: In cardiovascular disease, numerous evidence-based prognostic models have been created, usually based on regression analyses of isolated patient datasets. They tend to focus on one outcome event, based on just one baseline evaluation of the patient, and fail to take the disease process in its dynamic nature into account. We present so-called microsimulation as an attractive alternative for clinical decision-making in individual patients. We aim to further familiarize clinicians with the concept of microsimulation and to inform them about the modeling process. Methods and Results: We describe the modeling process, advantages and disadvantages of microsimulation. We illustrate the concept using a hypothetical 60-year-old patient, with several cardiac risk factors, who is hospitalized for myocardial infarction. By using microsimulation, we calculate this patient’s probability of death. In our example, this particular patient’s estimated life expectancy turns out to be 8.9 years. While calculating this life expectancy, we were able to account for multiple outcome events and changing patient characteristics. Conclusions: Microsimulation takes into account the dynamic nature of coronary artery disease by estimating most likely outcomes regarding a broad range of clinical events. Moreover, microsimulation can be used to evaluate treatment effects by estimating the event-free life expectancy with and without treatment. Hence, microsimulation has several advantages compared to modeling techniques such as regression.

The new European Society of Cardiology guidelines on myocardial revascularisation: An appraisal (Article)

2012-01-01T00:00:00Z

The latest European Society of Cardiology (ESC) guidelines on myocardial revascularisation are reviewed. The nearly 300 recommendations make it difficult to apply them in their totality. The authors would propose 20-30 recommendations per guideline based on sound clinical evidence. Also, the scope of the current guidelines is very wide as it includes topics already incorporated in other guidelines, such as strategies for pre-intervention diagnosis and imaging as well as on secondary prevention. Some recommendations in the new guidelines are sensible and will not be disputed. In particular, the encouragement of a balanced multidisciplinary decision process (the 'heart team') is welcome. Although coronary revascularisation in unstable high risk patients is well accepted, this is less the case for the low risk patient with chest pain. This issue is controversial and a balanced discussion of the pros and cons of percutaneous coronary intervention is missing. Despite convincing evidence indicating lack of benefit of percutaneous coronary intervention for chronic total occlusion, this procedure is not discouraged. Lastly, most committee members were interventional cardiologists or cardiac surgeons. Guideline committees should be representative of the whole group of professionals as the interpretation of the evidence by specialists may be biased. There may be a role for procedure oriented guidelines but, in that case, the items at issue should remain confined to matters directly related to technical aspects of the procedure.

Changes in clinical profile, treatment, and mortality in patients hospitalised for acute myocardial infarction between 1985 and 2008 (Article)

2011-11-02T00:00:00Z

Objectives: To quantify the impact of the implementation of treatment modalities into clinical practice since 1985, on outcome of patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). Methods: All consecutive patients admitted for STEMI or NSTEMI at the Thoraxcenter between 1985 and 2008 were included. Baseline characteristics, pharmacological and invasive treatment modalities, and survival status were collected. The study population was categorised in three groups of patients: those hospitalised between 1985-1990, 1990-2000, and 2000-2008. Results: We identified 14,434 patients hospitalised for myocardial infarction (MI). Both STEMI and NSTEMI patients were increasingly treated with the current guideline based therapy. In STEMI, at 30 days following admission, cumulative mortality rate decreased from 17% in 1985-1990 to 13% in 1990-2000, and to 6% in 2000-2008. Adjusted 30-day and three-year mortality in the last period was 80% and 68% lower than in 1985, respectively. In NSTEMI, at 30 days following admission, cumulative mortality rate decreased from 6% in 1985-1990 to 4% in 1990-2000, and to 2% in 2000-2008. Adjusted 30-day and three-year mortality in the last period was 78% and 49% lower than in 1985, respectively. For patients admitted between 2000 and 2008, 3 year survival of STEMI and NSTEMI patients was 87% and 88%, respectively. Conclusions: Our results indicate substantial improvements in acute- and long-term survival in patients hospitalised for MI, related to improved acute- as well as long-term treatment. Early medical evaluation in suspected MI and intensive early hospital treatment both remain warranted in the future.

Aortic homograft endocarditis caused by Campylobacter jejuni (Article)

2011-11-01T00:00:00Z

We report the first case of homograft endocarditis caused by Campylobacter jejuni, which was treated successfully with antibiotic therapy and valve replacement. To our knowledge, only two other cases of C. jejuni endocarditis, involving native valves, have been reported in the medical literature. Copyright

Measures of body composition and risk of heart failure in the elderly: The Rotterdam study (Article)

2011-05-01T00:00:00Z

Objectives: The incidence of heart failure increases with aging. Aim of the present, study was to determine whether measures body composition predict incident heart failure in older adults. Selling: Prospective community-based cohort study. 5, 868 men and women aged 55 years and older participating the Rotterdam study. Measures of body mass index and waist circumference were obtained at baseline. Information on incident heart failure was obtained during follow-up. Cox regression analyses were performed to investigate the possible association between measure of body composition and incident heart failure. Results: During a mean follow up of 10.9 (SD ±4.4) years, 765 participants had heart failure. After adjustment for age and gender, 1-standard deviation of body mass index, waist circumference and the waist-hip ratio predicted heart failure (HR 1.25; 95% CI 1.17-1.34; HR 1.26; 95% CI 1.18-1.36; and HR 1.17; 95% CI 1.08-1.27), respectively. In age-stratified analyses, 1-standard deviation of body mass index (1.17; 95% CI 1.06-1.29) and waist circumference (1.16; 95% CI 1.05-1.29) were still associated with the risk of heart failure in the oldest participants, whereas the waist-hip ratio was not (1.06; 95% CI 0.945-1.18). Conclusion: Although estimates decrease with age, measures of overall and central adiposity predict incident heart failure among community dwelling older adults.

Statins for primary prevention of cardiovascular disease. (Article)

2011-03-30T00:00:00Z

Variation in the von Willebrand factor gene is associated with von Willebrand factor levels and with the risk for cardiovascular disease (Article)

2011-01-27T00:00:00Z

High levels of von Willebrand factor (VWF) are associated with an increased risk for cardiovascular disease (CVD). Although VWF levels are strongly heritable and genetic susceptibility is an important risk factor for CVD, information on the contribution of common VWF gene variants to VWF levels and CVD risk is limited. In a case-control study of 421 young patients with a first event of acute coronary heart disease (CHD) or ischemic stroke (IS), and 409 healthy control participants (men aged ≤ 45 years, women aged ≤ 55 years), 27 haplotypetagging single-nucleotide polymorphisms (ht-SNPs), covering the total common VWF gene variation, were selected and genotyped. The associations between these SNPs, VWF antigen (VWF:Ag) levels, VWF collagen-binding (VWF:CB) activity, and CVD risk was investigated. Two new associations were identified. For ht-SNP rs4764478 (intron 45), the increase in VWF:Ag levels and VWF:CB activity per minor allele was 0.082 (± 0.026) IU/mL (P = .001) and 0.096 (± 0.030) IU/mL (P = .002), respectively. ht-SNP rs216293 (intron 17) was associated with CVD risk (odds ratio, 1.44; 95% confidence interval [CI], 1.12-1.86 per minor allele). We confirmed the association between rs1063857 and CVD risk. Our data show that common variants in the VWF gene are associated with VWF levels and with the risk for CVD.

Statins and all-cause mortality in high-risk primary prevention of patients with cardiovascular risk factors (Article)

2010-12-13T00:00:00Z

Effect of genetic variations in syntaxin-binding protein-5 and syntaxin-2 on von willebrand factor concentration and cardiovascular risk (Article)

2010-12-01T00:00:00Z

Background - Elevated von Willebrand factor (VWF) plasma levels are associated with an increased risk of cardiovascular disease. A meta-analysis of genomewide association studies on VWF identified novel candidate genes, that is, syntaxin-binding protein 5 (STXBP5) and syntaxin 2 (STX2), which are possibly involved in the secretion of VWF. We investigated whether VWF antigen levels (VWF:Ag), VWF collagen-binding activity (VWF:CB) and the risk of arterial thrombosis are affected by common genetic variations in these genes. Methods and Results - In 463 young white subjects (men ≤45 years of age and women ≤55 years of age), who were included 1 to 3 months after a first event of arterial thrombosis, and 406 control subjects, we measured VWF:Ag and VWF:CB. Nine haplotype tagging single-nucleotide polymorphisms of STXBP5 and STX2 were selected and subsequently analyzed using linear regression with additive genetic models adjusted for age, sex, and ABO blood group. The minor alleles of rs9399599 and rs1039084 in STXBP5 were associated with lower VWF plasma levels and activity, whereas the minor allele of rs7978987 in STX2 was associated with higher VWF plasma levels and activity. The minor alleles of the single-nucleotide polymorphisms in STX2 were associated with a reduced risk of arterial thrombosis (rs1236: odds ratio, 0.73 [95% confidence interval, 0.59, 0.89]; rs7978987: odds ratio, 0.81 [95% confidence interval, 0.65, 1.00]; rs11061158: odds ratio, 0.69 [95% confidence interval, 0.55, 0.88]). Conclusions-Genetic variability in STXBP5 and STX2 affects both VWF concentration and activity in young individuals with premature arterial thrombosis. Furthermore, in our study, genetic variability in STX2 is associated with the risk of arterial thrombosis. However, at this point, the underlying mechanism remains unclear.

Statin prescription in men and women at cardiovascular risk: To whom and when? (Article)

2010-09-01T00:00:00Z

PURPOSE OF REVIEW: To review the recent evidence of the effectiviness of statin therapy in the primary prevention of cardiovascular disease in men and women without established cardiovascular disease (CVD). RECENT FINDINGS: The use of statins in patients without established CVD has important public health implications. Until recently, research has provided ambiguous answers and the reliability of treatment in older people (>65 years), women, and patients with diabetes has remained uncertain, mainly because of a lack of data or inconsistent findings within these clinically defined groups. The Justification for the use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) demonstrated a significant benefit of rosuvastatin in low-risk patients with no apparent vascular disease, low-density lipoprotein levels of less than 3.4 mmol/l, and elevated high sensitivity C-reactive protein. The latest meta-analysis of statins in 70 000 patients without established CVD confirmed the overall benefit of statins in these low-risk patients and found no significant heterogeneity of the treatment effect in the clinically defined subgroups of elderly (>65 years), women, and patients with diabetes. SUMMARY: The use of statins in low-risk patients without CVD remains a matter of intense debate, even following the latest findings from the JUPITER. Statins reduce cardiovascular risk and mortality in this patient category. However, the overall absolute risk reductions and cost-effectiveness of long-term statin prescription should be kept in mind before prescribing statins to relatively healthy individuals. The exact threshold of baseline risk of CVD has not been determined yet and is a challenge for emerging treatment guidelines in primary prevention.

Unrecognised myocardial infarction and long-term risk of heart failure in the elderly: The Rotterdam study (Article)

2010-09-01T00:00:00Z

Objective: To examine the association between unrecognised myocardial infarction (MI) as detected by electrocardiography and the long-term risk of heart failure. Design: The Rotterdam Study is a prospective population-based cohort study of the general population of a suburb of the city of Rotterdam, The Netherlands. Participants: At baseline 2581 men and 3724 women aged ≥55 years were classified on the basis of electrocardiography, interview and clinical data into those with recognised MI, those with ECG-based unrecognised MI and those without MI. The participants were followed-up for incident heart failure, death or end of the study period on 12 October 2006. Results: During a median follow-up time of 13.2 years, 823 cases of heart failure occurred, of which 403 in men. Independently of cardiovascular risk factors, recognised and unrecognised MIs yielded HRs of developing heart failure in men of 2.6 (95% CI 2.0 to 3.3) and 2.1 (95% CI 1.5 to 2.9), respectively. In women, recognised MI was associated with heart failure (HR=2.8; 95% CI 1.9 to 4.1), whereas unrecognised MI was not significantly related to the risk of heart failure (HR=1.1; 95% CI 0.7 to 1.7). Conclusion: Unrecognised MI detected by electrocardiography yields a long-term risk of heart failure equivalent to recognised MI in men, but is not significantly related to heart failure in women. In the light of the high incidence of both unrecognised MI and heart failure in the elderly, it may be worthwhile for both doctors and patients to improve responsiveness to typical and atypical symptoms of MI.

Distribution of echocardiographic parameters and their associations with cardiovascular risk factors in the Rotterdam Study (Article)

2010-07-01T00:00:00Z

Insight into echocardiographic parameters in the general population may facilitate early recognition of ventricular dysfunction, reducing the population morbidity and mortality of heart failure. We examined the distribution of structural, systolic and diastolic echocardiographic parameters and their associations with cardiovascular risk factors in the Rotterdam Study, a population-based cohort study in men and women aged ≥55 years. Participants with prevalent heart failure, myocardial infarction and atrial fibrillation and flutter were excluded. Echocardiographic parameters were assessed using two-dimensional, M-mode and Doppler echocardiography. Echocardiograms were available in 4,425 participants. Structural parameters were generally larger in men, and most consistently associated with age, body mass index and blood pressure in both sexes. Prevalence of moderate or poor left ventricular systolic function was 3.9% in men and 2.1% in women. Age, body mass index and blood pressure were most consistently associated with systolic function. E/A ratio was lower in women than in men. Age and diastolic blood pressure were most consistently associated with E/A ratio in both sexes. In conclusion, ventricular systolic and diastolic dysfunction is present in asymptomatic individuals. Selected established cardiovascular risk factors are associated with structural, systolic and diastolic parameters.

Clinical synergy of perindopril and calcium-channel blocker in the prevention of cardiac events and mortality in patients with coronary artery disease. Post hoc analysis of the EUROPA study (Article)

2010-05-01T00:00:00Z

Background: The purposes of the study were to determine the effects of addition of perindopril to long-term continuous treatment with calcium-channel blocker (CCB) on cardiac outcomes in the stable coronary artery disease (CAD) population of EUROPA and to explore the presence of synergy between perindopril and CCB in secondary prevention. Methods: We identified participants receiving CCB at every visit during the 4.2-year follow-up and analyzed the effect of addition of perindopril (n = 1,022 perindopril/CCB vs n = 1,100 placebo/CCB). Results: Addition of perindopril to CCB significantly reduced total mortality by 46% (P < .01 vs placebo) and primary end point (a composite of cardiovascular mortality, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 35% (P < .05 vs placebo). There were 41%, 54%, and 28% reductions in cardiovascular mortality, hospitalization for heart failure, and myocardial infarction, respectively. Comparison of hazard ratios suggests the presence of a clinical synergy between perindopril and CCB, with a greater effect than addition of individual effects. Conclusion: Addition of perindopril to CCB in stable CAD patients had a significant supplementary impact on cardiac outcomes and mortality.

Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients (Article)

2009-11-01T00:00:00Z

ADAMTS13 may play a role in arterial thrombosis by cleaving the highly active and thrombogenic ultralarge Von Willebrand Factor (VWF) multimers into less active VWF multimers. The aim was to investigate the relationship between plasma levels of ADAMTS13, VWF and genetic variation in the ADAMTS13 gene with cardiovascular disease. We performed a case-control study in 374 patients with a first-ever arterial thrombosis before the age of 45 years in males and 55 years in women. We included 218 patients with coronary heart disease (CHD), 109 patients with ischemic stroke (IS) and 47 patients with peripheral arterial disease (PAD) and 332 healthy population-based controls. ADAMTS13 and VWF levels were measured 1-3 months after the event. ADAMTS13 levels were associated with cardiovascular disease (OR antigen 5.1 (95% CI 3.1-8.5, p < 0.001) and OR activity 4.4 (95% CI 2.5-7.5, p < 0.001), in the lowest quartiles). VWF levels were associated with cardiovascular disease (OR antigen 2.1 (95% CI 1.3-3.3, p = 0.001) and OR activity 2.0 (95% CI 1.3-3.1, p = 0.003), in the highest quartile). Patients with combined low ADAMTS13 levels and high VWF levels had an odds ratio of 7.7 (95% CI 3.3-17.7) (p for trend <0.0001). No association was found between genetic variation in the ADAMTS13 gene with levels of ADAMTS13 or with risk of cardiovascular disease. In conclusion, levels of ADAMTS13 and VWF are strongly associated with the risk of cardiovascular disease.

The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. (Article)

2009-07-20T00:00:00Z

OBJECTIVES: To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. DESIGN: Meta-analysis of randomised trials. DATA SOURCES: Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I(2) statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. RESULTS: 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. CONCLUSION: In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.

Genetic variants associated with cardiac structure and function: A meta-analysis and replication of genome-wide association data (Article)

2009-07-08T00:00:00Z

Context: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. Objective: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Design, Setting, and Participants: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n=12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n=4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10-7to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Main Outcome Measures: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. Results: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1%of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). Conclusions: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.

The role of thrombin activatable fibrinolysis inhibitor in arterial thrombosis at a young age: The ATTAC study (Article)

2009-05-29T00:00:00Z

Background and objectives: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and may therefore contribute to the pathophysiology of arterial thrombosis. The aim of the present study was to elucidate the pathogenetic role of TAFI levels and genotypes in young patients with arterial thrombosis. Patients and methods: In a case-control study, 327 young patients with a recent first-ever event of coronary heart disease (CHD subgroup) or cerebrovascular disease (ischemic stroke subgroup) and 332 healthy young controls were included. TAFI levels [intact TAFI, activation peptide (TAFI-AP) and (in)activated TAFI (TAFIa(i)] and TAFI activity were measured and genetic variations in the TAFI gene (-438G/A, 505G/A and 1040C/T) were determined. Results: In the total group of patients, TAFIa(i) levels were higher (145.1 ± 37.5%) than in controls (137.5 ± 31.3%, P = 0.02). Plasma levels of intact TAFI, TAFI-AP and TAFI activity were similar in patients and controls. In the CHD subgroup (n = 218), intact TAFI levels were higher (109.4 ± 23.0%) than in controls (102.8 ± 20.7%, P = 0.02). In 325Ile/Ile homozygotes, lower TAFI levels and a decreased risk of arterial thrombosis were observed (OR 0.58, 95% CI 0.34-0.99) compared with patients with the common 325Thr/Thr genotype. This association was most evident in CHD patients (OR 0.48, 95% CI 0.26-0.90). Haplotype analyses supported a role for the Thr325Ile polymorphism. Conclusions: TAFIa(i) levels were higher in patients with cardiovascular disease. Furthermore, the TAFI 325Thr/Ile polymorphism was associated with lower TAFI levels and with the risk of cardiovascular disease in young patients, especially in CHD.

Echocardiographic parameters and all-cause mortality: The Rotterdam Study (Article)

2009-04-03T00:00:00Z

Background: Even when heart failure has not yet become clinically manifest, preclinical ventricular dysfunction may be present, and therapeutic interventions introduced at this time may reduce morbidity and mortality. However, data on the predictive value of echocardiographic characteristics in the general population remain relatively scarce. Methods: The Rotterdam Study is a population-based cohort study in men and women aged ≥ 55 years. Participants with prevalent heart failure, myocardial infarction and atrial fibrillation and flutter at the time of echocardiography were excluded. Structural, systolic and diastolic parameters were assessed using two-dimensional, M-mode and Doppler echocardiography. Echocardiograms were available in 4425 participants. Results: During a mean follow-up of 3.0 years, 226 participants died. Increased left ventricular mass was an independent risk factor for all-cause mortality, particularly in men (hazard ratio per standard deviation of natural log transformed left ventricular mass, 1.20 (95% CI, 1.01-1.43)). Fractional shortening and left ventricular systolic function did not show a clear association with mortality. E/A ratio < 0.75 was an independent risk factor in men (age-adjusted hazard ratio 1.82 (95% CI 1.23-2.69)). This was further reflected by diastolic function: impaired relaxation was a risk factor in men, but not in women. Conclusions: Structural and diastolic echocardiographic parameters are associated with all-cause mortality in an asymptomatic population. However, the evidence is still inadequate to support the usefulness of echocardiography for screening to identify asymptomatic individuals with preclinical ventricular dysfunction.

Hypofibrinolysis is a risk factor for arterial thrombosis at young age (Article)

2009-04-01T00:00:00Z

The relationship between defective fibrinolysis and arterial thrombosis is uncertain. The evaluation of the plasma fibrinolytic potential might provide stronger evidence linking fibrinolysis to arterial thrombosis than the evaluation of the individual fibrinolytic factors. We determined the plasma fibrinolytic potential of 335 young survivors of a first arterial thrombosis, including coronary artery disease (n = 198), ischaemic stroke (n = 103) and peripheral artery disease (n = 34), enrolled in a population-based case-control study and of 330 healthy individuals. Patients had significantly higher clot lysis times (CLTs) than the controls. Odds ratios (ORs) were calculated as a measure of relative risk. The OR for arterial thrombosis was determined in these subjects who had a CLT above the 60th, 70th, 80th, 90th and 95th percentiles of the values found in the control subjects. We found a progressive increase in risk of arterial thrombosis in subjects with hypofibrinolysis (OR: 1·7, 2·0, 2·3, 2·3 and 2·9, respectively). Relative risk estimates obtained in the whole group were comparable those obtained in the event-subgroups. In conclusion, a low plasma fibrinolytic potential, found in 10% of the population, increases the relative risk of arterial thrombosis twofold. This points to an important contribution of hypofibrinolysis to the burden of arterial thrombosis.

Secondary prevention of coronary disease with ACE inhibition-does blood pressure reduction with perindopril explain the benefits in EUROPA? (Article)

2009-04-01T00:00:00Z

Aims: We determined whether blood pressure (BP) lowering by perindopril was related to its benefit in the EUROPA study. Methods and results: Twelve thousand two hundred eighteen patients with documented coronary artery disease received perindopril 8 mg once daily or matching placebo after a 4-week run-in period in which all patients received perindopril. Patients were excluded if systolic (S) BP was >180 or <100 mmHg. Mean age was 60 years (range 26-89). 27% had a history of hypertension. After 4.2 years of follow-up, the primary endpoint (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) was observed in 603 (9.9%) placebo versus 488 (8.0%) perindopril patients [20% relative risk reduction (RRR), CI 9-29%, P∈=∈0.003]. There was no interaction between baseline SBP levels (using JNC-7 cutoff values) and treatment effect. If anything, the greatest RRR of the primary endpoint (32%) occurred in patients with the lowest SBP (<120 mmHg) in whom perindopril did not reduce SBP. Also, RRR during blinded treatment was comparable, irrespective of whether BP decreased or not or of the extent of BP reduction during perindopril treatment. Conclusion: The treatment benefit in EUROPA cannot be fully explained by baseline BP or BP reduction with perindopril. Other mechanisms including direct anti-atherosclerotic effects of ACE inhibition may play a role.

N-terminal pro-brain natriuretic peptide testing in the emergency department: Beneficial effects on hospitalization, costs, and outcome (Article)

2008-07-01T00:00:00Z

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) is an established biomarker for heart failure. Assessment of this biomarker in patients with acute dyspnea presenting to the emergency department (ED) may aid diagnostic decision-making, resulting in improved patient care and reduced costs. Methods: In a prospective clinical trial, patients presenting with acute dyspnea to the ED of the Erasmus Medical College, Rotterdam, the Netherlands, were randomized for either rapid measurement or no measurement of NT-proBNP. For ruling out heart failure, cutoff values of 93 pg/mL in male and 144 pg/mL in female patients were used, and for ruling in heart failure, a cutoff value of 1,017 pg/mL was used. Time to discharge from the hospital and costs related to hospital admission were primary end points. Bootstrap analysis was used for comparison of costs and 30-day mortality between the NT-proBNP and control group. Results: A total of 477 patients (54% male) was enrolled. The mean age was 59 years, with 44% of patients having a history of cardiac disease. Median time to discharge from the hospital was 1.9 days (interquartile range [IQR], 0.12-8.4 days) in the NT-proBNP group (n = 241) compared with 3.9 days (IQR, 0.16-11.0 days) in the control group (n = 236) (P = .04). Introduction of NT-proBNP testing resulted in a trend toward reduction in costs related to hospital admission and diagnostic investigations of $1,364 per patient (95% CI $-246 to $3,215), whereas 30-day mortality was similar (15 patients in the NT-proBNP and 18 patients in the control group). Conclusions: Introduction of NT-proBNP testing for heart failure in the ED setting reduces the time to discharge and is associated with a trend toward cost reduction.

Frequency of the von Willebrand factor Tyr1584Cys polymorphism in arterial thrombosis [1] (Article)

2008-03-01T00:00:00Z

ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis: Results from the PERTINENT study (Article)

2008-01-01T00:00:00Z

The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-α), and a biomarker of thrombosis, d-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-α, and d-dimer in 291 patients. There was no significant effect of treatment on CRP or fibrinogen. In contrast, there were significant reductions in TNF-α (27.60-25.20 pg/mL; P < 0.05) and d-dimer (0.24-0.18 μg/mL; P < 0.05) with perindopril over 1 year. Survival analysis of the prognostic significance of baseline CRP failed to detect a significant role for the prediction of cardiovascular events over 4 years (lower versus higher tertile: 1.54; 95% confidence interval 0.88-2.68; P = 0.16). In conclusion, in the PERTINENT trial, we observed significant effects of ACE inhibition on biomarkers of the atherothrombotic complications (d-dimer) and the proinflammatory cytokine TNF-α, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen).

The Cardioprotective Effects of the Angiotensin-Converting Enzyme Inhibitor Perindopril in Patients With Stable Coronary Artery Disease Are Not Modified by Mild to Moderate Renal Insufficiency. Insights From the EUROPA Trial (Article)

2007-11-27T00:00:00Z

Objectives: This study sought to examine whether the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitor therapy by perindopril are modified by renal function in patients with stable coronary artery disease. Background: A recent study reported that an impaired renal function identified a subgroup of patients with stable coronary artery disease more likely to benefit from ACE inhibition therapy. In light of the growing interest in tailored therapy for targeting medications to specific subgroups, remarks on the consistency of the treatment effect by ACE inhibitors are highly important. Methods: The present study involved 12,056 patients with stable coronary artery disease without heart failure randomized to perindopril or placebo. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease equation. Cox regression analysis was used to estimate multivariable-adjusted hazard ratios. Results: The mean eGFR was 76.2 (±18.1) ml/min/1.73 m2. During follow-up, the primary end point (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) occurred in 454 of 5,761 patients (7.9%) with eGFR ≥75 and in 631 of 6,295 patients (10.0%) with eGFR <75. Treatment benefits of perindopril were apparent in both patient groups either with eGFR ≥75 (hazard ratio 0.77; 95% confidence interval 0.64 to 0.93) or eGFR <75 (hazard ratio 0.84; 95% confidence interval 0.72 to 0.98). We observed no significant interaction between renal function and treatment benefit (p = 0.47). Using different cutoff points of eGFR at the level of 60 or 90 resulted in similar trends. Conclusions: The treatment benefit of perindopril is consistent and not modified by mild to moderate renal insufficiency.

Insight into ACE inhibition in the prevention of cardiac events in stable coronary artery disease: The EUROPA trial (Article)

2007-11-01T00:00:00Z

The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) investigated the effect of angiotensin-converting enzyme inhibition on the prevention of cardiac events in patients with stable coronary artery disease (CAD) without apparent heart failure. Perindopril 8 mg/day significantly reduced a composite outcome of cardiovascular death, nonfatal myocardial infarction or resuscitated cardiac arrest by 20% compared with placebo, in addition to standard preventive therapies. This review describes the substudies and subpopulation analyses carried out within the EUROPA population, concluding that the benefits of perindopril extend to all stable CAD patients, even revascularized patients or those with preserved left ventricular function. Data on the pathophysiological mechanisms underlying CAD indicate direct vascular protection with perindopril. This helps explain why perindopril is beneficial in preventing cardiac events in stable CAD patients.

Cost effectiveness of perindopril in reducing cardiovascular events in patients with stable coronary artery disease using data from the EUROPA study (Article)

2007-09-01T00:00:00Z

Background: The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported. Objective: To assess the cost effectiveness of perindopril in stable coronary heart disease in the UK. Methods: Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health-related quality of life values were taken from published sources. A cost-effectiveness analysis is presented as a function of the risk of a primary event (non-fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money. Results: The median incremental cost of perindopril for each quality-adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as £9700 (interquartile range £6400-£14 200). Overall, 88% of the EUROPA population had an estimated cost per QALY below £20 000 and 97% below £30 000. For a threshold value of cost effectiveness of £30 000 per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care. Conclusions: Whether the use of perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.

Long-Term Effect of Perindopril on Coronary Atherosclerosis Progression (from the PERindopril's Prospective Effect on Coronary aTherosclerosis by Angiography and IntraVascular Ultrasound Evaluation [PERSPECTIVE] Study) (Article)

2007-07-15T00:00:00Z

The multicenter EUROPA trial of 12,218 patients showed that perindopril decreased adverse clinical events in patients with established coronary heart disease. The PERSPECTIVE study, a substudy of the EUROPA trial, evaluated the effect of perindopril on coronary plaque progression as assessed by quantitative coronary angiography and intravascular ultrasound (IVUS). In total 244 patients (mean age 57 years, 81% men) were included. Evaluable paired quantitative coronary angiograms were obtained from 96 patients randomized to perindopril and from 98 patients to placebo. Concomitant treatment at baseline consisted of aspirin (90%), lipid-lowering agents (70%), and β blockers (60%). The primary and secondary end point was the difference of minimum and mean lumen diameters (quantitative coronary angiography) or mean plaque cross-sectional area (IVUS) measured at baseline and 3-year follow-up between the perindopril and placebo groups. After a median follow-up of 3.0 years (range 1.9 to 4.1), no differences in change in quantitative coronary angiographic or IVUS measurements were detected between the perindopril and placebo groups (minimum and mean luminal diameters -0.07 ± 0.4 vs -0.02 ± 0.4 mm, p = 0.34; mean luminal diameter -0.05 ± 0.2 vs -0.05 ± 0.3 mm, p = 0.89; mean plaque cross-sectional area -0.18 ± 1.2 vs -0.02 ± 1.2 mm2, p = 0.48). In conclusion, we found no progression in coronary artery disease by quantitative coronary angiography and IVUS with long-term administration of perindopril or placebo, possibly because most patients were on concomitant treatment with a statin.

Efficacy of perindopril in reducing risk of cardiac events in patients with revascularized coronary artery disease (Article)

2007-04-01T00:00:00Z

Background: The aim of the study was to assess the effect on cardiac events of adding perindopril 8 mg once daily to standard preventive therapy in the subgroup of EUROPA patients with previous revascularization and without previous myocardial infarction (MI). Methods: We conducted a subgroup analysis of the EUROPA study patients according to their revascularization and previous MI history. Among the 12 218 patients of EUROPA, we identified 6709 (54.9%) patients who had a previous revascularization. Approximately equal proportions had undergone percutaneous coronary intervention (3122) or coronary artery bypass grafting (3136). Of the revascularized patients, 3047 (24.9%) patients had not experienced a previous MI. Results: Out of the 6709 revascularized patients, 3340 were treated with perindopril and 3369 with placebo. Baseline characteristics were similar to the whole EUROPA population in terms of demographics, medical history, physical examination (heart rate, blood pressure), and medications at screening. The mean patient age was 60 years, and 85% were men. The relative risk reduction with perindopril 8 mg was 17.3% (95% CI 1.3%-30.8%, P = .035) for the composite primary end point of cardiovascular death, nonfatal MI, and resuscitated cardiac arrest and was 23% (95% CI 4.9%-37.6%, P = .015) for fatal and nonfatal MI. In the 3047 revascularized patients without a history of MI, perindopril was associated with a relative risk reduction of 31.7% for fatal and nonfatal MI (95% CI 4.4%-51.2%, P = .026). Conclusion: Perindopril 8 mg daily is beneficial for primary and secondary prevention of cardiac events in patients with coronary artery disease without clinical evidence of heart failure including those with previous revascularization.

Evaluation of a hand carried cardiac ultrasound device in an outpatient cardiology clinic (Article)

2005-01-01T00:00:00Z

OBJECTIVE: To determine the diagnostic potential of a hand carried cardiac ultrasound (HCU) device (OptiGo, Philips Medical Systems) in a cardiology outpatient clinic and to compare the HCU diagnosis with the clinical diagnosis and diagnosis with a full featured standard echocardiography (SE) system. METHODS: 300 consecutive patients took part in the study. The HCU examination was performed by an experienced echocardiographer before patients visited the cardiologist. The echocardiographer noted whether the HCU device was able to confirm or reject the referral diagnosis, which abnormality was detected, and whether SE investigation was necessary. Physical examination by a cardiologist followed and thereafter, whenever required, a complete study with an SE was carried out. The HCU data were compared with the clinical diagnosis of the cardiologist and the SE diagnosis in a blinded manner. RESULTS: The cardiologist referred 203 of 300 patients for an SE study and 13 patients for transoesophageal echocardiography. In 84 patients no further examination was considered necessary. HCU echocardiography was able to confirm or reject the suspected clinical diagnosis in 159 of 203 (78%) patients. In 44 of 203 (22%) patients SE Doppler was needed. Agreement between the HCU device and the SE system for the detection of major abnormalities was excellent (98%). The HCU device missed 4% of the major findings. Among the 84 patients not referred for an SE, the HCU device detected unsuspected major abnormalities missed with the physical examination in 14 (17%). CONCLUSION: Integration of an HCU device with the physical examination augments the yield of information.

Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects. (Article)

2004-12-01T00:00:00Z

AIMS: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects. METHODS AND RESULTS: We investigated 4264 normotensive and 2174 hypertensive participants of the Rotterdam Study, a population based prospective cohort study. All subjects were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart failure in normotensive subjects were the same over all genotype strata (10 per 1000 person-years). In hypertensive subjects, the IR increased with the number of D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years). Hypertensive subjects carrying the II-genotype did not have an increased risk of heart failure compared to normotensive II subjects. However, hypertensive subjects carrying one or two copies of the D-allele did have a significantly increased risk of heart failure (ID: RR: 1.4 (1.1-1.9) and DD: RR: 1.5 (1.2-2.1)). CONCLUSION: Our findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.

Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. (Article)

2004-09-01T00:00:00Z

AIMS: To determine the prevalence, incidence rate, lifetime risk and prognosis of heart failure. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based cohort study in 7983 participants aged > or =55. Heart failure was defined according to criteria of the European Society of Cardiology. Prevalence was higher in men and increased with age from 0.9% in subjects aged 55-64 to 17.4% in those aged > or =85. Incidence rate of heart failure was 14.4/1000 person-years (95% CI 13.4-15.5) and was higher in men (17.6/1000 man-years, 95% CI 15.8-19.5) than in women (12.5/1000 woman-years, 95% CI 11.3-13.8). Incidence rate increased with age from 1.4/1000 person-years in those aged 55-59 to 47.4/1000 person-years in those aged > or =90. Lifetime risk was 33% for men and 29% for women at the age of 55. Survival after incident heart failure was 86% at 30 days, 63% at 1 year, 51% at 2 years and 35% at 5 years of follow-up. CONCLUSION: Prevalence and incidence rates of heart failure are high. In individuals aged 55, almost 1 in 3 will develop heart failure during their remaining lifespan. Heart failure continues to be a fatal disease, with only 35% surviving 5 years after the first diagnosis.

Insulin-like growth factor-I gene polymorphism and risk of heart failure (the Rotterdam Study) (Article)

2004-08-01T00:00:00Z

We studied 4,963 participants of the population-based Rotterdam Study and found that a genetically determined chronic exposure to low insulin-like growth factor-I (IGF-I) levels is associated with an increased risk for heart failure in elderly patients.

Continuously improving the practice of cardiology (Article)

2004-01-01T00:00:00Z

Guidelines for the management of patients with cardiovascular disease are designed to assist cardiologists and other physicans in their practice. Surveys are conducted to assess whether guidelines are followed in practice. The results of surveys on acute coronary syndromes, coronary revascularisation, secondary prevention, valvular heart disease and heart failure are presented. Comparing surveys conducted between 1995 and 2002, a gradual improvement in use ofsecondary preventive therapy is observed. Nevertheless, important deviations from established guidelines are noted, with a significant variation among different hospitals in the Netherlands and in other European countries. Measures for fiuther improvement of clinical practice indude more rapid treatment of patients with evolving myocardial infarction, more frequent use of clopidogrel and glycoprotein IIb/IIIa receptor blockers in patients with acute coronary syndromes, more frequent use of 5-blockers in patients with heart failure and more intense measures to encourage patients to stop smoking. Targets for the proportion ofpatients who might receive specific therapies are presented.

Patients with acute coronary syndromes without persistent ST elevation undergoing percutaneous coronary intervention benefit most from early intervention with protection by a glycoprotein IIb/IIIa receptor blocker. (Article)

2002-02-01T00:00:00Z

BACKGROUND: Many patients with acute coronary syndromes are offered percutaneous coronary intervention. However, the appropriate indications for, and optimal timing of, such procedures are uncertain. We analysed timing of intervention and associated events (death and myocardial infarction) in the PURSUIT trial in which 9461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide, or placebo for 72 h. Other treatment was left to the investigators. 2430 patients underwent percutaneous coronary intervention within 30 days. Four groups were distinguished, who underwent percutaneous coronary intervention on day 1; on days 2 or 3; at 4 to 7 days; or between 8 until 30 days, for eptifibatide- and placebo-treated patients. RESULTS: The four groups treated with placebo demonstrated total 30-day events of 15.9% for day 1 percutaneous coronary intervention, 17.7%, 15.0% and 18.2%, respectively, for successive intervals of later intervention. Later intervention was associated with more pre-procedural events (2.2% to 13.7%, P=0.001) which was balanced by a decrease in procedure-related events (12.1 to 3.1%, P=0.001), while the overall 30-day event rates were similar. Eptifibatide-treated patients with percutaneous coronary intervention on day 1 had the lowest rate of 30-day events (9.2%, P<0.05 vs other groups). In this group, pre-procedural risk was only 0.3%, while percutaneous coronary intervention on eptifibatide treatment was associated with low procedural risk (7.2%). The total 30-day event rate for later percutaneous coronary intervention in patients receiving eptifibatide was 14.0 on days 2 and 3, 15.0% for days 4 to 7 and 17.4% for days 7 to 30, respectively. CONCLUSION: Patients treated with a platelet glycoprotein IIb/IIIa receptor blocker, and early percutaneous coronary intervention (within 24 h) had the lowest event rate in this post hoc analysis. Thus 'watchful waiting' may not be the optimal strategy. Rather an early invasive strategy with percutaneous coronary intervention under protection of a platelet glycoprotein IIb/IIIa receptor blocker should be considered in selected patients. Randomized trials are warranted to verify this issue.

Systematic adjudication of myocardial infarction end-points in an international clinical trial. (Article)

2001-09-04T00:00:00Z

BACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment) myocardial infarction (MI) in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial. METHODS: The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. RESULTS: The CEC identified 5005 patients with suspected infarction (46%), of which 1415 (28%) were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. CONCLUSIONS: End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates.

Disagreements between central clinical events committee and site investigator assessments of myocardial infarction end-points in an international clinical trial: review of the PURSUIT study (Article)

2001-09-04T00:00:00Z

Abstract: Background Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and those adjudicated by a central clinical events committee (CEC) to determine the reasons for differences in event rates. Methods The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. The primary end-point was death or post-enrolment MI at 30 days as assessed by the CEC; this end-point was also constructed using site-reported events. The CEC identified suspected MIs by systematic review of clinical, cardiac enzyme, and lectrocardiographic data. Results The CEC identified 5005 (46%) suspected events, of which 1415 (28%) were adjudicated as MI. The site investigator and CEC assessments of whether a MI had occurred disagreed in 983 (20%) of the 5005 patients with suspected MI, mostly reflecting site misclassification of post-enrolment MIs (as enrolment MIs) or underreported periprocedural MIs. Patients for whom the CEC and site investigator agreed that no end-point MI had occurred had the lowest mortality at 30 days and between 30 days and 6 months, and those with agreement that a MI had occurred had the highest mortality. Conclusion CEC adjudication provides a standard, systematic, independent, and unbiased assessment of end-points, particularly for trials that span geographic regions and clinical practice settings. Understanding the review process and reasons for disagreement between CEC and site investigator assessments of MI is important to design future trials and interpret event rates between trials.

The prognosis of heart failure in the general population: The Rotterdam Study. (Article)

2001-08-22T00:00:00Z

AIMS: To determine the prognosis, cause of death, and its determinants in participants of the population-based Rotterdam Study who were found to have heart failure. METHODS AND RESULTS: In 5255 Rotterdam Study participants (aged 68.9+/-8.6 years, 3113 women) the presence of heart failure was determined. Data were analysed with Cox's proportional-hazards models. One hundred and eighty-one participants (age 77.3+/-7.9 years, 109 women) had heart failure. Of these 85 (47%) died during the 4.8-8.5 (mean 6.1) years of follow-up. One, 2 and 5 years' survival was 89%, 79%, and 59%, representing an age-adjusted mortality twice that of persons without heart failure (hazard ratio 2.1, 95% CI 1.8-2.7). The hazard ratio for sudden death was even more pronounced: 4.8, (95% CI 2.6-8.7). Diabetes mellitus, impairment of renal function and atrial fibrillation were associated with a poor outcome. A higher blood pressure and body mass index conferred a more favourable prognosis in those with heart failure. CONCLUSION: Heart failure generally afflicts older subjects in the community, carries a poor prognosis, especially in the presence of concomitant diseases, and confers a fivefold increase in the risk of sudden death.

Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty (Article)

2001-01-01T00:00:00Z

OBJECTIVE: Lefradafiban is the orally active prodrug of fradafiban, a glycoprotein IIb/IIIa receptor antagonist. The present phase II study aimed to determine the dose of lefradafiban that provides 80% blockade of the glycoprotein IIb/IIIa receptors by fradafiban, and to study the pharmacodynamics and safety of different doses in patients with stable angina undergoing angioplasty. DESIGN: A double blind, placebo controlled, dose finding study. SETTING: Four academic and community hospitals in the Netherlands. PATIENTS: 64 patients with stable coronary artery disease undergoing elective percutaneous transluminal coronary angioplasty. INTERVENTIONS: 30 mg, 45 mg, and 60 mg of lefradafiban three times daily or placebo was given for 48 hours. MAIN OUTCOME MEASURES: The primary safety end point was the occurrence of bleeding, classified as major, minor, or insignificant according to the thrombolysis in myocardial infarction (TIMI) criteria. Efficacy indices included per cent fibrinogen receptor occupancy (FRO), ex vivo platelet aggregation, and plasma concentrations of fradafiban. RESULTS: Administration of lefradafiban 30, 45, and 60 mg three times daily resulted in a dose dependent increase in median FRO levels of 71%, 85%, and 88%, respectively. Inhibition of platelet aggregation was closely related to FRO. There were no major bleeding events. The 60 mg lefradafiban group had a high (71%) incidence of minor and insignificant bleeding. The incidence of bleeding was 44% in the 30 mg and 45 mg groups, compared with 9% in placebo patients. Puncture site bleeding was the most common event. The odds of bleeding increased by 3% for every 1% increase in FRO. CONCLUSIONS: Lefradafiban is an effective oral glycoprotein IIb/IIIa receptor blocker. The clinical effectiveness of doses up to 45 mg three times daily should be investigated.

Risk of stroke associated with abciximab among patients undergoing percutaneous coronary intervention (Article)

2001-01-01T00:00:00Z

CONTEXT: Abciximab, a potent inhibitor of the platelet glycoprotein IIb/IIIa receptor, reduces thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). Because of its potent inhibition of platelet aggregation, the effect of abciximab on risk of stroke is a concern. OBJECTIVE: To determine whether abciximab use among patients undergoing PCI is associated with an increased risk of stroke. DESIGN: Combined analysis of data from 4 double-blind, placebo-controlled, randomized trials (EPIC, CAPTURE, EPILOG, and EPISTENT) conducted between November 1991 and October 1997 at a total of 257 academic and community hospitals in the United States and Europe. PATIENTS: A total of 8555 patients undergoing PCI with or without stent deployment for a variety of indications were randomly assigned to receive a bolus and infusion of abciximab (n = 5476) or matching placebo (n = 3079). One treatment group in EPIC received a bolus of abciximab only. MAIN OUTCOME MEASURE: Risk of hemorrhagic and nonhemorrhagic stroke within 30 days of treatment among abciximab and placebo groups. RESULTS: No significant difference in stroke rate was observed between patients assigned abciximab (n = 22 [0.40%]) and those assigned placebo (n = 9 [0.29%]; P =.46). Excluding the EPIC abciximab bolus-only group, there were 9 strokes (0.30%) among 3023 patients who received placebo and 15 (0.32%) in 4680 patients treated with abciximab bolus plus infusion, a difference of 0.02% (95% confidence interval [CI], -0.23% to 0.28%). The rate of nonhemorrhagic stroke was 0.17% in patients treated with abciximab and 0.20% in patients treated with placebo (difference, -0.03%; 95% CI, -0.23% to 0.17%), and the rates of hemorrhagic stroke were 0.15% and 0.10%, respectively (difference, 0.05%; 95% CI, -0.11% to 0.21%). Among patients treated with abciximab, the rate of hemorrhagic stroke in patients receiving standard-dose heparin in EPIC, CAPTURE, and EPILOG was higher than in those receiving low-dose heparin in the EPILOG and EPISTENT trials (0.27% vs 0.04%; P =.057). CONCLUSIONS: Abciximab in addition to aspirin and heparin does not increase the risk of stroke in patients undergoing PCI. Patients undergoing PCI and treated with abciximab should receive low-dose, weight-adjusted heparin.

Safety and preliminary efficacy of one month glycoprotein IIb/IIIa inhibition with lefradafiban in patients with acute coronary syndromes without ST-elevation; a phase II study. (Article)

2000-12-01T00:00:00Z

AIMS: Oral glycoprotein IIb/IIIa inhibitors might enhance the early benefit of an intravenous agent and prevent subsequent cardiac events in patients with acute coronary syndromes. We assessed the safety and preliminary efficacy of 1 month treatment with three dose levels of the oral GP IIb/IIIa blocker lefradafiban in patients with unstable angina or myocardial infarction without persistent ST elevation. METHODS: The Fibrinogen Receptor Occupancy STudy (FROST) was designed as a dose-escalation trial with 20, 30 and 45 mg lefradafiban t.i.d. or placebo. Five hundred and thirty-one patients were randomized in a 3:1 ratio to lefradafiban or placebo in a double-blind manner. Efficacy was assessed by the incidence of death, myocardial infarction, coronary revascularization and recurrent angina. Safety was evaluated by the occurrence of bleeding classified according to the TIMI criteria and by measuring clinical laboratory parameters. RESULTS: There was a trend towards a reduction in cardiac events with lefradafiban 30 mg when compared with placebo and lefradafiban 20 mg. The benefit was particularly apparent in patients with a positive (> or = O.1 ng. ml(-1)) troponin I test at baseline and less so in those with a negative test result. In patients receiving lefradafiban, the cardiac event rate decreased with increasing minimal levels of fibrinogen receptor occupancy. There was a dose-dependent increase in the incidence of bleeding: the composite of major or minor bleeding occurred in 1% of placebo patients, 5% of patients receiving lefradafiban 20 mg and in 7% of patients receiving 30 mg, with an excessive risk (15%) in the 45 mg group which resulted in early discontinuation of this dose level. Gingival and arterial or venous puncture site bleedings were most common and accounted for more than 60% of all haemorrhagic events. There was an increased incidence of neutropenia (neutrophils <1. 5 x 10(9)/l) in the lefradafiban groups (5.2% vs 1.5% in the placebo group), which did not result from bone marrow depression but rather from a reversible redistribution of neutrophils by margination or clustering. CONCLUSION: One month's treatment with the oral glycoprotein IIb/IIIa inhibitor lefradafiban in patients with unstable angina and myocardial infarction without persistent ST elevation resulted in a decrease in cardiac events with lefradafiban 30 mg and a dose-dependent increase in haemorrhagic events. The observed favourable trend towards a reduction in cardiac events in patients with elevated troponin levels requires confirmation in a large clinical trial.

Prospective study of early discharge after acute myocardial infarction (SHORT) (Article)

2000-06-15T00:00:00Z

Aims To identify, without additional investigation, a large group of myocardial infarction patients at low risk who would qualify for early discharge. Methods The decision rule was developed in 647 unselected patients with consecutively admitted myocardial infarction, and validated in 825 others. Daily event-rates were calculated for major (death, ventricular fibrillation, recurrent infarction, heart failure, advanced AV-block) and minor (unstable angina and rhythm-abnormalities) cardiac complications. Results Patients free from major complications until day 7 (44% of all patients) were found to constitute a very low risk group and thus would qualify for discharge at day 7. Of the 39% of patients with an uncomplicated infarction (low risk) in the validation group, 31% were discharged at day 7, while 8% stayed longer because of non-cardiac co-morbidity, for social reasons or logistic problems. No major adverse event occurred within 7 days after hospital discharge and only 1·8% developed complications within 1 month. The median duration of hospital stay for all in-hospital survivors was 7 days compared to 10 days in the control group. Conclusion Prospective application of the early discharge decision rule, based upon simple clinical variables and without the need for additional non-invasive and/or invasive tests, resulted in a significant reduction of hospital stay. The decision rule correctly classified patients into high and low risk groups and appeared feasible and safe. Its efficacy was demonstrated by its ability to identify a large group of post infarction survivors at low risk for complications during follow-up.

Geographic variability in outcomes within an international trial of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes. Results from PURSUIT. (Article)

2000-03-04T00:00:00Z

AIMS: Variations in outcome of patients from different geographic regions have been observed in many large international trials. We analysed the factors that might contribute to the geographic variations in patient outcome and treatment effect as observed in the PURSUIT trial. METHODS: In PURSUIT, 9461 patients with acute coronary syndromes without persistent ST-elevation were randomized to the platelet inhibitor eptifibatide or placebo for 72 h in 27 countries in four geographic regions: Western (n=3697) and Eastern Europe (n=1541) as well as North (n=3827) and Latin America (n=396). The primary end-point was the 30-day composite of death or myocardial infarction. In the initial univariate analysis, the treatment effect appeared greater in N. America than in W. Europe, while no benefit was apparent in L. America and E. Europe. However, the confidence intervals were wide and overlapping. To study these differences, a subdivision in an early and late patient outcome and treatment effect was made. Accordingly, we analysed the rate of death or infarction at 72 h censored for percutaneous coronary intervention and the rate between 3 and 30 days, respectively. Additional analyses were performed with different definitions of myocardial infarction using progressively higher thresholds of CK(-MB) elevation. Multivariable analysis was used to evaluate the relation between region and outcome and to determine the adjusted odds ratios for the eptifibatide treatment effect. RESULTS: Major differences in baseline demographics were apparent among the four regions; in particular, more patients from E. Europe had characteristics associated with impaired outcome. Interventional treatment also varied considerably, with more patients from N. America undergoing revascularization. Despite differences in the 72 h event rate, eptifibatide showed a consistent trend towards a reduction in the composite end-point among all four regions and for all definitions of infarction. Relative reductions ranged from 17-42% in W. Europe, 23-35% in N. America, 0-33% in E. Europe, and 55-82% in L. America. After multivariable adjustment, the pattern of benefit with eptifibatide was consistent among the regions. In patients undergoing percutaneous coronary intervention during study drug infusion in W. Europe (n=266) and N. America (n=931), the relative reduction in myocardial infarction during medical therapy ranged from 56-75% in W. Europe and 14-67% in N. America, while the reduction in procedure-related events ranged from 12-44% and 25-61% for different definitions of infarction. After multivariable adjustment neither benefit nor rebound were apparent after study drug discontinuation, or after 3 days in all regions, except in L. America. In general, the differences in outcome and treatment effect were greatest when the protocol definition of myocardial infarction (CK(-MB) >1 upper normal limit) was applied. Under stricter definitions, these differences became smaller and disappeared with the investigator's assessment. CONCLUSION: The analysis suggests that the apparent differences in patient outcome and eptifibatide treatment effect can be explained largely by differences in baseline demographics and adjunctive treatment strategies as well as by the methodology of myocardial infarction definition and the adjudication process.

Cigarette smoking status and outcome among patients with acute coronary syndromes without persistent ST-segment elevation: Effect of inhibition of platelet glycoprotoin IIb/IIIa with eptifibatide (Article)

2000-01-01T00:00:00Z

BACKGROUND: Studies have shown that cigarette smokers constitute a substantial proportion of patients with acute coronary syndromes (ACS) and have platelet-rich coronary thrombi. We characterized the influence of smoking status on outcome of patients with ACS without persistent ST-segment elevation and tested the hypothesis that selective inhibition of the platelet glycoprotein IIb/IIIa receptor with eptifibatide would improve outcomes among cigarette smokers. METHODS: The study population included patients enrolled in the PURSUIT trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) with known smoking status presenting with ischemic chest pain

Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. (Article)

2000-01-01T00:00:00Z

CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation. OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased. DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997. PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization. MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality. RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both). CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.

Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators (Article)

2000-01-01T00:00:00Z

BACKGROUND: Appropriate treatment policies should include an accurate estimate of a patient's baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation. METHODS AND RESULTS: We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81). CONCLUSIONS: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process.

Registration and management of smoking behaviour in patients with coronary heart disease. The EUROASPIRE survey. (Article)

1999-11-01T00:00:00Z

AIMS: To establish to what extent smoking status and its management is recorded in coronary patients' medical records, and to investigate their motivation to change smoking behaviour. METHODS: In EUROASPIRE, a survey on secondary prevention in 21 hospitals in the Czech Republic, Finland, France, Germany, Hungary, Italy, the Netherlands, Slovenia and Spain, data were collected from records of 4863 consecutive patients =<70 years of age, with previous (>6 months) admission for coronary bypass operation, angioplasty, myocardial infarction or ischaemia. Of these, 3569 patients were interviewed 1.6 years following their index hospitalization. RESULTS: Of the 82% of patients whose pre-hospitalization smoking behaviour was known, 34% were smokers. Documentation was significantly better in younger patients, in males and patients requiring angioplasty or bypass operation. In only 35% of 1364 smokers was the smoking habit recorded again after discharge from hospital At the time of the interview, 554 of the interviewed patients were still smoking. In over 90% of the smokers, advice to quit smoking was reported at interview. A positive relationship was found between receiving advice and seeking help to stop smoking, between receiving advice to stop smoking and attempting to stop, as well as between seeking help and attempting to stop. CONCLUSION: In almost 20% of coronary patients, smoking habits are not documented in medical records, and in only 35% of the smoking patients is smoking status documented at the follow-up. After a cardiac event requiring hospitalization as many as 50% of patients continue their smoking habit and so there is further potential to reduce the risk of recurrent coronary disease. Advice to stop smoking motivates patients to seek help and to attempt to stop smoking. Physicians repeated advice to stop smoking is important and smoking status should always be documented at follow-up.

Anticoagulant properties, clinical efficacy and safety of efegatran, a direct thrombin inhibitor, in patients with unstable angina. (Article)

1999-08-01T00:00:00Z

AIMS: Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and efficacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. METHODS: Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0.105 mg. kg(-1). h(-1)to 1.2 mg. kg(-1). h(-1)over 48 h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. Efficacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. RESULTS: Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1.2 mg. kg(-1). h(-1)resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant differences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients. CONCLUSION: Administration of efegatran sulphate at levels of at least 0.63 mg. kg(-1). h(-1)provided an anti-thrombotic effect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent.

Sustained benefit at 10-14 years follow-up after thrombolytic therapy in myocardial infarction (Article)

1999-06-01T00:00:00Z

AIMS: To investigate whether the benefit of thrombolytic therapy was sustained beyond the first decade. We report the 10-14 year outcome of 533 patients who were randomized to treatment with intracoronary streptokinase or to conventional therapy during the years 1980-1985. METHODS AND RESULTS: Details of survival and cardiac events were obtained from the civil registry, from medical records or from the patient's physician. At follow-up, 158 patients (59%) of the 269 patients allocated to thrombolytic treatment and only 129 patients (49%) of the 264 conventionally treated patients were alive. The cumulative 1-, 5- and 10-year survival rates were 91%, 81% and 69% in patients treated with streptokinase and 84%, 71% and 59% in the control group, respectively (P=0.02). Reinfarction during 10-years of follow-up was more frequent after thrombolytic therapy, particularly during the first year. Coronary bypass surgery and coronary angioplasty were more frequently performed after thrombolytic therapy. At 10 years approximately 30% of the patients were free from subsequent cardiac events.Independent determinants of mortality were elderly age, indicators of impaired residual left ventricular function, multivessel disease and an inability to perform an exercise test at the time of hospital discharge. CONCLUSION: Improved survival after thrombolytic therapy is maintained beyond the first decade. Age, left ventricular function, multivessel disease and an inability to perform an exercise test were independent predictors for long-term mortality, as they are predictors for early mortality.

Clinical Significance of Thrombocytopenia During a Non-ST-Elevation Acute Coronary Syndrome (Article)

1999-01-01T00:00:00Z

BACKGROUND: The significance of thrombocytopenia in patients experiencing an acute coronary syndrome (ACS) has not been examined systematically. We evaluated this condition in a large non-ST-elevation ACS clinical trial, with particular interest paid to its correlation with clinical outcomes. METHODS AND RESULTS: Patients presenting without persistent ST elevation during an ACS were randomized to receive a double-blind infusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor eptifibatide or placebo in addition to other standard therapies including heparin and aspirin. The primary end point was death/nonfatal myocardial infarction (MI) at 30 days, whereas bleeding and stroke were the main safety outcomes. Thrombocytopenia (nadir platelet count <100x10(9)/L or <50% of baseline) occurred in 7.0% of enrolled patients. The time to onset was a median of 4 days in both treatment arms. Patients with thrombocytopenia were older, weighed less, were more likely nonwhite, and had more cardiac risk factors. These patients experienced significantly more bleeding events: they were more than twice as likely to experience moderate/severe bleeding after adjustment for confounders. Univariably, ischemic events (stroke, MI, and death) occurred significantly (P<0.001) more frequently in patients with thrombocytopenia; multivariable regression modeling preserved this association with death/nonfatal MI at 30 days. Neither the use of heparin or eptifibatide was found to independently increase thrombocytopenic risk. CONCLUSIONS: Although causality between thrombocytopenia and adverse clinical events could not be established definitively, thrombocytopenia was highly correlated with both bleeding and ischemic events, and the presence of this condition identified a more-at-risk patient population.

Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study (Article)

1999-01-01T00:00:00Z

AIMS: To determine the prevalence of heart failure and symptomatic as well as asymptomatic left ventricular systolic dysfunction in the general population. METHODS AND RESULTS: In 5540 participants of the Rotterdam Study (age 68.9+/-8.7 years, 2251 men) aged 55-95 years, the presence of heart failure was determined by assessment of symptoms and signs (shortness of breath. ankle oedema and pulmonary crepitations) and use of heart failure medication. In 2267 subjects (age 65.7+/-7.4 years, 1028 men) fractional shortening was measured. The overall prevalence of heart failure was 3.9% (95% CI 3.0+/-4.7) and did not differ between men and women. The prevalence increased with age, with the exception of the highest age group in men. Fractional shortening was higher in women and did not decrease appreciably with age. The prevalence of left ventricular systolic dysfunction (fractional shortening <=25%) was approximately 2.5 times higher in men (5.5%, 95% CI 4.1-7.0) than in women (2.2%, 95% CI 1.4-3.2). Sixty percent of persons with left ventricular systolic dysfunction had no symptoms or signs of heart failure at all. CONCLUSIONS: The prevalence of heart failure is appreciable and does not differ between men and women. The majority of persons with left ventricular systolic dysfunction can be regarded as having asymptomatic left ventricular systolic dysfunction.

Stroke in Patients With Acute Coronary Syndromes: Incidence and Outcomes in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial (Article)

1999-01-01T00:00:00Z

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.

The cardiac infarction injury score as a predictor for long-term mortality in survivors of a myocardial infarction (Article)

1998-01-01T00:00:00Z

AIMS: The Cardiac Infarction Injury Score (CIIS) is an electrocardiographic classification system that was developed as a diagnostic tool to assess the extent of cardiac injury in acute myocardial infarction. We investigated the prognostic value of the CIIS in post-myocardial infarction patients. METHODS AND RESULTS: The prognostic values of the CIIS for total and cardiac mortality was assessed in a large series (n = 3395) of patients who were enrolled in the ASPECT trial. Standard 12-lead electrocardiograms, recorded prior to hospital discharge were coded according to the CIIS and the Minnesota Code. Mean CIIS was 26 (range--8 to 59). After adjustment for other baseline characteristics, the CIIS was directly related to the risk of total mortality and cardiac mortality. At one-year follow-up the relative risks of CIIS > or = 40, CIIS 30-40 and CIIS 20-30 were significantly higher than in those with a CIIS < 20. The relative risks were, respectively, 2.3 (1.2-4.4), 2.2 (1.3-3.9) and 1.6 (0.9-2.9). At 3 year follow-up, the relative risks were, respectively, 2.1 (1.4-3.2), 1.7 (1.2-2.4) and 1.5 (1.0-2.1). The relative risks for total mortality were similar. When patients with major ECG abnormalities, as defined by the Minnesota code, were excluded, the associations were still significant in the CIIS classes 30-40 and > 40. CONCLUSION: The CIIS ECG scoring system is an important predictor for long-term cardiac mortality in post myocardial infarction patients. It can easily be automated and is efficient for classifying cardiac injury in epidemiological studies.

Estimated gain in life expectancy (Article)

1996-01-01T00:00:00Z

Currently several modes of reperfusion therapy for acute myocardial infarction are available. Streptokinase, accelerated alteplase and direct angioplasty are the most frequently used. These options are increasingly effective, but are also increasingly complex and costly. Since, unfortunately, physicians are often restricted by budget limitations, choices must be made in clinical practice to provide optimal therapy to individual patients. In order to guide such decision making, we developed a model to predict the expected benefit of therapy in terms of gain in life expectancy. Patients' life expectancy will decrease after infarction. Part of this loss can be prevented by early reperfusion therapy. The clinical benefit of therapy ranges from negligible gain in patients with small infarcts treated relatively late to an expected gain of more than 2 years in patients with extensive infarction treated within 3 h of onset of symptoms. The expected benefits are presented in a set of tables and depend on age, previous infarction, estimated infarct size, treatment delay and intracranial bleeding risk. With the help of these table, resources will be allocated in such a manner that patients who will benefit the most will receive the most effective therapy. Patients with similar expected treatment benefit will be offered the same mode of therapy. Future life years were discounted at 5% per year. The arbitrary thresholds currently applied for decision making at the Thoraxcenter are: no reperfusion therapy when the estimated gain in discounted life expectancy was < 1 month, streptokinase for 1-4 months and accelerated alteplase for a gain >or = 5 months. Direct angioplasty is recommended in patients with an estimated gain > or = 12 months, and in patients with an increased risk of intracranial bleeding. In this way, approximately 80% of our patients will be treated with thrombolytics (40% streptokinase and 40% accelerated alteplase), while in 10% direct angioplasty will be initiated. Patients with small infarcts presenting late will not receive reperfusion therapy. These threshold values have been chosen arbitrarily, and different thresholds may be selected in other centres. However, the developed model would guarantee that treatment decisions are made in a consistent manner, to provide optimal therapy for patients with evolving myocardial infarction, in spite of limited resources.

Implementation of a pre-hospital decision rule in general practice. Triage of patients with suspected myocardial infarction (Article)

1996-01-01T00:00:00Z

OBJECTIVE: To improve pre-hospital triage of patients with suspected acute cardiac disease. DESIGN: Prospective study. SUBJECTS. Patients with symptoms suggestive of acute cardiac pathology, who were seen by a general practitioner, for whom acute admission into hospital was requested, and in whom a pre-hospital electrocardiogram was recorded by the ambulance service. METHODS: The study consisted of two phases. In the first phase, a decision rule was developed based on clinical characteristics and electrocardiographic findings in 1005 patients with suspected acute cardiac pathology. In the second phase, the decision rule was prospectively validated. Symptoms were recorded by a standardized questionnaire by the general practitioner and a computerized electrocardiogram was made by the ambulance nurses at the patient's home. Three electrocardiographic outcomes were available: 'normal electrocardiogram', 'possible myocardial infarction' or 'extensive myocardial infarction'. By use of the predictive model, the general practitioner could decide if hospitalization was necessary or not. MAIN OUTCOME MEASUREMENTS: Identification of patients at low (stable angina, atypical chest pain, other pathology) and high (myocardial infarction, unstable angina) probability of acute cardiac pathology. RESULTS: Among 977 patients with a complete pre-hospital evaluation in the validation phase of the study, the decision rule recommended 'no hospitalization' in 227 patients (23%). The general practitioner followed this advice in 44% of these patients. Although seven of them developed a non-Q wave myocardial infarction, no complications occurred in patients not admitted. In addition, the general practitioner did not hospitalize 19 (2%) of 750 patients for whom the decision rule recommended admission. Pre-hospital triage by the general practitioner resulted in a 12% (118 of 977 patients) reduction of the number of patients admitted to the Coronary Care Units. CONCLUSIONS: Pre-hospital triage by the general practitioner was facilitated using a standardized questionnaire and pre-hospital electrocardiography, and resulted in a reduction in the number of patients admitted to the Coronary Care Unit, and proved to be safe.

Clinical perspective. Coronary artery disease: prevention of progression and prevention of events (Article)

1995-01-01T00:00:00Z

Bevordering van snelle en gerichte verwijzing van patienten met een mogelijk hartinfarct door ECG thuis (Article)

1995-01-01T00:00:00Z

Snelle en adequate behandeling van patiënten met een hartinfarct is levensreddend en beperkt de schade aan de hartspier (infarctgrootte). Niet alleen de duur, maar ook de kwaliteit van het leven na een infarct wordt zo verbeterd. Levensbedreigende ritmestoornissen, met name ventrikelfibrilleren, kunnen worden gedetecteerd door middel van elektrocardiografische bewaking, en kunnen doorgaans adequaat worden behandeld met defibrillatie en resuscitatie. Reperfusie van de bij het infarct afgesloten coronairarterie leidt tot herstel van de bloedtoevoer naar het bedreigde myocard, zodat de ischemische myocyten kunnen herstellen en de infarctgrootte wordt beperkt. Indien reperfusietherapie kan worden gestart binnen 3 h na het begin van de klachten van een infarct, daalt het sterfterisico met maar liefst gemiddeld 50. Toediening tussen 3 en 6 h vermindert het sterfterisico met ongeveer 25 en latere toediening, tot 12 h, met ongeveer 12,5.1 Hoe vroeger, hoe ... etc.

Editorial: New directions in anticoagulant and antiplatelet treatment (Article)

1995-01-01T00:00:00Z

Pre-hospital thrombolytic therapy with either alteplase or streptokinase. Practical applications, complications and long-term results in 529 patients (Article)

1995-01-01T00:00:00Z

OBJECTIVE: To assess the practical application, safety and long-term outcome of pre-hospital thrombolytic intervention with either alteplase or streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more than 30 min duration, presenting within 6 h of symptom onset and with electrocardiographic evidence of extensive evolving myocardial infarction. METHODS: Eligibility of patients was established by the general practitioner or the ambulance nurse using a standardized questionnaire with (contra-) indications for thrombolytic therapy. Computerized ECG was recorded by ambulance nurses. In the presence of extensive ST segment elevation (sum ST deviation of at least 1.0 mV), eligible patients received either 100 mg alteplase (n = 246) or 50 mg alteplase in the ambulance followed by 0.75 x 10(6) IE streptokinase in hospital (n = 90), or 1.5 x 10(6) IE streptokinase intravenously (n = 193). MAIN OUTCOME MEASUREMENTS: Death and life-threatening complications (ventricular fibrillation, cardiac arrest) and side effects (hypotension, allergic reactions) during transportation to hospital and in the first 24 h following hospitalization, and survival up to 5 years follow-up. RESULTS: From 1988-1993, 529 patients received thrombolytic treatment initiated pre-hospital. The time gained by pre-hospital administration of thrombolysis amounted to 50 min. The rate of complications during transportation and during the first 24 h after hospitalization was low. Hospital mortality was 2% and 1-year mortality 3%. Cumulative survival at 5 years was 92%. This was superior to the 84% 5-year survival observed in a matched group of 239 patients with similar baseline characteristics treated with alteplase in hospital. CONCLUSIONS: Pre-hospital administration of either alteplase or streptokinase is feasible and safe and results in significant time gain. The long-term prognosis is excellent in spite of extensive evolving myocardial infarction upon admission.

Acute and long-term outcome of directional coronary atherectomy for stable and unstable angina (Article)

1994-10-05T00:00:00Z

The clinical efficacy and safety of directional coronary atherectomy for the treatment of stable and unstable angina were assessed in 82 patients with stable and 68 patients with unstable angina. Therefore, clinical and angiographic follow-up was obtained in a prospectively collected consecutive series of 150 atherectomy procedures. Restenosis was assessed clinically and by quantitative angiography. The overall clinical success rate of atherectomy for patients with unstable and stable angina was 88% and 91%, respectively. No significant differences were found for in-hospital event rates between the unstable and stable angina groups: death (1.5% vs 0%), myocardial infarction (10% vs 6%), and emergency bypass operation (3% vs 2%). These clinical events were related to the occurrence of abrupt occlusions (8.8% in patients with stable and 6.1% in those with unstable angina; p = NS). Clinical follow-up was achieved in 100% of the patients with stable and unstable angina at a mean interval of 923 and 903 days, respectively. Two-year survival rates were 96% and 97% in the populations with unstable and stable angina, respectively. There were no significant differences with respect to bypass surgery and angioplasty, but event-free survival at 2 years was significantly lower in the unstable (54%) than the stable (69%) angina group. Quantitative coronary angiography did not detect any difference in luminal renarrowing during the 6-month angiographic follow-up period. Although directional coronary atherectomy can be performed effectively in patients with unstable and stable angina, the long-term clinical outcome was less favorable in the unstable angina group.(ABSTRACT TRUNCATED AT 250 WORDS)

Complicaties kort na percutane transluminale angioplastiek of na coronariachirurgie bij 183 vergelijkbare patienten met een meervatscoronaria-aandoening (Article)

1994-01-01T00:00:00Z

Acute and long-term outcome of directional coronary atherectomy for stable and unstable angina (Article)

1994-01-01T00:00:00Z

Verbetering opname-beleid op de hartbewakingseenheden (Article)

1993-03-05T00:00:00Z

Which angiographic variable best describes functional status 6 months after successful single-vessel coronary balloon angiopasty? (Article)

1993-01-01T00:00:00Z

OBJECTIVES. The aim of this study was to determine which quantitative angiographic variable best describes functional status 6 months after coronary balloon angioplasty. BACKGROUND. Several angiographic restenosis criteria have been developed. These can be divided into those that describe the change in lesion severity and those that merely describe lesion severity at follow-up angiography. The functional significance of these criteria is unknown. METHODS. We studied 350 patients with single-vessel coronary artery disease who underwent a single-site balloon dilation. Sensitivity and specificity curves were constructed for the prediction of anginal status and exercise electrocardiography of four quantitative angiographic variables that describe restenosis. The point of highest diagnostic accuracy for the variables was determined at the intersection of the sensitivity and specificity curves. Results of exercise electrocardiography were considered indicative for ischemia 6 months after angioplasty if horizontal or downsloping ST segment depression > or = 1 mm occurred. RESULTS. The points of highest diagnostic accuracy of the angiographic variables were similar for both anginal status and exercise electrocardiography: 1.45 and 1.46 mm for the minimal lumen diameter measurements, 45.5% and 46.5% for the percent diameter stenosis measurements at follow-up, -0.30 and -0.32 mm for change in minimal lumen diameter and -10% and -10% for the change in percent diameter stenosis at follow-up. CONCLUSIONS. Angiographic variables reflecting a change in lesion severity at follow-up angiography were only slightly less accurate than variables that describe lesion severity at follow-up. The large study group and the fact that the same optimal values for diagnostic accuracy of the various quantitative angiographic variables were obtained for the prediction of two different markers of ischemia suggests that these values reflect the lesion severity or increase in lesion severity in major epicardial vessels at which coronary flow reserve is unable to meet myocardial demands.

Safety and efficacy of recombinant Hirudin (CGP 39 393) versus Heparin in patients with stable angina undergoing coronary angioplasty (Article)

1993-01-01T00:00:00Z

BACKGROUND. Enhanced thrombin activity has been associated with acute and long-term complications following balloon angioplasty (percutaneous transluminal coronary angioplasty (PTCA). We evaluated, in a 2-to-1 randomized, double-blind trial, the effects of recombinant hirudin, CGP 39 393, relative to unfractionated sodium heparin on periprocedural events, bleeding, early angiographic outcome, and coagulation in 113 patients with stable angina undergoing PTCA. METHODS AND RESULTS. Prior to PTCA, 20 mg CGP 39 393 was administered as a bolus, followed by continuous infusion at a rate of 0.16 mg.kg-1 x h-1, or 10,000 IU sodium heparin was administered as a bolus and continued at a rate of 12 IU.kg-1 x h-1 for 24 hours. Infusion was adjusted to activated partial thromboplastin time (APTT) levels. ST segment was monitored for 24 hours, and angiograms were analyzed with quantitative technique (QCA). In 74 CGP 39 393- and 39 heparin-treated patients, 132 lesions were dilated. Myocardial infarction and/or emergency coronary bypass surgery occurred in 1 (1.4%) CGP 39 393 patient compared with 4 (10.3%) heparin patients (relative risk, 7.6; 95% confidence interval, 0.9, 65.6). At 24 hours, complete perfusion was present in 91% heparin and 100% CGP 39 393 patients. Significant ST segment displacement was found in 11% of heparin versus 4% of CGP 39 393 subjects. Bleeding occurred only at the puncture site in 4 CGP 39 393-treated patients. QCA did not reveal significant differences between the groups. APTT values were more often in the target range and more stable in CGP 39 393 patients. Levels of thrombin-antithrombin III complexes, prothrombin fragment F1+2, and fibrinopeptide A indicated that CGP 39 393 was an effective inhibitor of thrombin activity. CONCLUSIONS. CGP 39 393 can safely be administered to patients undergoing elective PTCA for stable anginal symptoms and may have a more favorable anticoagulant profile than heparin.

Usefulness of repeat coronary angiography 24 hours after balloon angioplasty to evaluate early lminal deterioration and facilitate quantitative analysis (Article)

1993-01-01T00:00:00Z

Because of the unavoidable occurrence of vessel disruption after successful coronary balloon angioplasty, the reliability of quantitative angiographic analysis in that setting has been questioned. For this reason and the suggested occurrence of delayed elastic recoil, repeat angiography at 24 hours has been advocated in clinical interventional trials. In this study, these issues are confronted by performing comprehensive quantitative analysis (Cardiovascular Angiographic Analysis System) of coronary angiograms, acquired in multiple identical projections immediately after and 24 hours after angioplasty, in 102 patients with 110 successfully dilated lesions. Vasomotion was controlled by intracoronary nitrate before angiography and all patients were fully anticoagulated (activated partial thromboplastin time 85 to 120 seconds) for > 24 hours. Paired Student's t tests applied to angiographic measurements revealed that there was no significant deterioration in minimal luminal diameter or cross-sectional area from immediately after angioplasty to 24 hours later. It can thus be inferred that there is no phenomenon of delayed elastic recoil, at least during this time period. Measurement accuracy and precision of the Cardiovascular Angiographic Analysis System from the postangioplasty angiogram are highly acceptable, at < 0.01 and +/- 0.20 mm, respectively. Therefore, it is concluded that routine repeat 24-hour angiography is not indicated after successful angioplasty. A highly significant increase (p < 0.001) in reference diameter (+0.11 +/- 0.18 mm) was responsible for the apparent increase in percent diameter stenosis (2.4 +/- 7%), a finding that demonstrates the potential for error by selective application of percent diameter stenosis measurements alone. Preferential use of absolute luminal measurements is thus strongly recommended for clinical trials with angiographic monitoring.

Het functioneren van een inspannings-elektrocardiografische service voor huisartsen; een beschrijving van 498 patienten (Article)

1993-01-01T00:00:00Z

Retardation and arrest of progression or regression of cronary artery disease : a review (Article)

1993-01-01T00:00:00Z

Lumen narrowing after percutaneous transluminal coronary balloon angioplasty follows a near gaussian distribution: a quantitative angiographic study in 1,445 successfully dilated lesions (Article)

1992-01-01T00:00:00Z

To determine whether significant angiographic narrowing and restenosis after successful coronary balloon angioplasty is a specific disease entity occurring in a subset of dilated lesions or whether it is the tail end of a gaussian distributed phenomenon, 1,445 successfully dilated lesions were studied before and after coronary angioplasty and at 6-month follow-up study. The original cohort consisted of 1,353 patients of whom 1,232 underwent repeat angiography with quantitative analysis (follow-up rate 91.2%). Quantitative angiography was carried out off-line in a central core laboratory with an automated edge detection technique. Analyses were performed by analysts not involved with patient care. Distributions of minimal lumen diameter before angioplasty (1.03 +/- 0.37 mm), after angioplasty (1.78 +/- 0.36 mm) and at 6-month follow-up study (1.50 +/- 0.57 mm) as well as the percent diameter stenosis at 6-month follow-up study (44 +/- 19%) were assessed. The change in minimal lumen diameter from the post-angioplasty angiogram to the follow-up angiogram was also determined (-0.28 +/- 0.52 mm). Seventy lesions progressed toward total occlusion at follow-up. All observed distributions approximately followed a normal or gaussian distribution. Therefore, restenosis can be viewed as the tail end of an approximately gaussian distributed phenomenon, with some lesions crossing a more or less arbitrary cutoff point, rather than as a separate disease entity occurring in some lesions but not in others.

Therapeutic dissection after successful coronary balloon angioplasty: no influence on restenosis or on clinical outcome in 693 patients. The MERCATOR Study Group (Multicenter European Research Trial with Cilazapril after Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis) (Article)

1992-01-01T00:00:00Z

OBJECTIVES: The objective of this study was to examine the relation between an angiographically visible coronary dissection immediately after successful coronary balloon angioplasty and a subsequent restenosis and long-term clinical outcome. BACKGROUND. The study population comprised all 693 patients who participated in the MERCATOR trial (randomized, double-blind, placebo-controlled restenosis prevention trial of cilazapril, 5 mg two times a day). METHODS. Cineangiographic films were processed and analyzed at a central angiographic core laboratory, without knowledge of clinical data, with use of an automated interpolated edge detection technique. Dissection was judged according to the National Heart, Lung, and Blood Institute classification. Angiographic follow-up was obtained in 94% of patients with 778 lesions. Two approaches were used to assess the restenosis phenomenon: 1) categoric, using the traditional cutoff criterion of greater than 50% diameter stenosis at follow-up, and 2) continuous, defined as absolute change in minimal lumen diameter (mm) between the postcoronary angioplasty and follow-up, adjusted for the vessel size (relative loss). Clinical outcome was ranked according to the most serious adverse clinical event per patient during the 6-month follow-up period, ranging from death, nonfatal myocardial infarction, coronary revascularization and recurrent angina requiring medical therapy to none of these. RESULTS. Dissection was present in 247 (32%) of the 778 dilated lesions. The restenosis rate was 29% in lesions with and 30% in lesions without dissection (relative risk 0.97; 95% confidence interval 0.77 to 1.23). The relative loss in both groups was 0.10 (mean difference 0; 95% confidence interval -0.03 to 0.03). Clinical outcome ranged from death in 4 patients (0.9%) without dissection and 1 patient (0.4%) with dissection; nonfatal myocardial infarction in 4 (0.9%) without and 8 (3.2%) with dissection; coronary revascularization in 73 (16.6%) without and 32 (12.7%) with dissection; recurrent angina requiring medical therapy in 88 (20%) without and 47 (18.7%) with dissection to no serious adverse event in 272 (61.7%) without and 114 (65.1%) with dissection. CONCLUSIONS. These data indicate that a successfully dilated coronary lesion with an angiographically visible dissection is no more likely to develop restenosis, and is not associated with a worse clinical outcome, at 6-month follow-up than is a dilated lesion without visible dissection on the post-balloon angioplasty angiogram.

Changes in the electrocardiographic response to exercise in healthy women (Article)

1990-01-01T00:00:00Z

Changes in the P wave, QRS complex, ST segment, and T wave during and after maximal exercise were quantitatively analysed in 116 healthy women with a mean age of 39. The corrected orthogonal Frank lead electrocardiogram was continuously recorded and computer processed during bicycle ergometry. With exercise, maximal spatial P wave vectors shifted downward. The Q wave amplitude became more negative and the R wave amplitude diminished considerably in leads X and Y: the S wave amplitude decreased only slightly in these leads. The QRS vectors shifted towards right and posteriorly during exertion and a further shift in the same direction was seen in the recovery period. The ST segment amplitude 60 ms after the J point decreased with exertion and became negative at heart rates above 140 beats per minute, in particular in lead Y. ST segment depression increased with age. The T wave amplitude decreased during exercise and increased sharply in the recovery period. Though mean R wave amplitude in leads X and Y became more negative with exercise, this response was unpredictable in individual women. The exercise induced changes in QRS vectors in women resembled those described in men. Changes in the amplitude of the R wave should not be used for the diagnosis of coronary disease in women. ST segment depression was more pronounced in the inferiorly oriented lead Y than in lead X but it was unrelated to changes in the QRS vectors in these leads.

A comparison of methods of analysing exercise tests for diagnosis of coronary artery disease (Article)

1989-01-01T00:00:00Z

The diagnostic accuracy of the following methods of analysing exercise tests were evaluated: (a) the cumulative area of ST segment depression during exercise normalised for workload and heart rate (exercise score); (b) discriminant analysis of electrocardiographic exercise variables, workload, and symptoms; and (c) ST segment amplitude changes during exercise adjusted for heart rate. Three hundred and forty five men without a history of myocardial infarction were studied. One hundred and twenty three were apparently healthy. Less than half (170) had coronary artery disease. All had a normal electrocardiogram at rest. A Frank lead electrocardiogram was computer processed during symptom limited bicycle ergometry. The accuracy of the exercise score (a) was low (sensitivity 67%, specificity 90%). Discriminant analysis (b) and ST segment amplitude changes adjusted for heart rate (c) had excellent diagnostic characteristics (sensitivity 80%, specificity 90%), which were little affected by concomitant use of beta blockers. Both methods seem well suited for diagnostic application in clinical practice.

Long-acting coronary vasodilatory action of the molsidomine metabolite Sin I: a quantitative angiographic study (Article)

1987-01-01T00:00:00Z

The vasodilatory action of molsidomine was studied by intracoronary injection of its active metabolite, Sin 1. In 10 patients repeat coronary angiography in multiple projections was performed before and 2 minutes after administration of 1 mg of Sin 1, and before and after a second injection 60 minutes later. Contours of obstructed and non-obstructed segments of the left coronary artery were quantitatively analysed with a computer-based angiography analysis system. Immediately after its administration, Sin 1 increased the mean diameters of 44 normal coronary segments by 12% (P less than 0.001). Significant vasodilation (8%) was still observed after 60 minutes. At that time, repeated administration of Sin 1 increased the vasodilation by an additional 14% with respect to the control situation. An increase in obstruction diameter was observed in 6 out of 8 obstructed segments. Mean increase in the minimal obstruction diameter was still 10% after 60 minutes.

Contribution of dynamic vascular wall thickening to luminal narrowing during coronary arterial vasomotion (In Book)

1984-01-01T00:00:00Z

Ineligibility for predischarge exercise testing after myocardial infarction in the elderly (Article)

1984-01-01T00:00:00Z

This study describes the clinical profile and prognosis of elderly patients not eligible for predischarge exercise testing. The database consisted of 133 patients 55-64 years of age, and 111 patients older than 64 years of age who survived an acute myocardial infarction. Follow-up was one year. In the younger age group, 24 (18%) patients were unable to perform the test, in contrast to 63 (57%) of the elderly subjects. In these two groups, one-year mortality rates were 13% and 37%, compared with 6% and 4% for the respective patients eligible for stress testing. Clinical profile and radionuclide ejection fraction between ineligible patients in both age groups were similar. Ejection fraction measurement was the best predictor of late mortality in those patients who did not have an exercise test. It is concluded that ineligibility for predischarge exercise test identifies a high-risk group, especially in patients older than 64 years of age.

Predischarge stress test after myocardial infarction in the old stage : results and prognostic value (Article)

1984-01-01T00:00:00Z

The aim of this study was to evaluate the results of predischarge stress testing in the elderly, and to assess the prognostic value of the test during one-year follow-up. The database consisted of 48 patients older than 64 years of age and 109 patients 55-64 years of age, who survived acute myocardial infarction, out of 532 consecutive patients admitted for myocardial infarction. Stress-test results were not different in the two groups. During one-year follow-up mortality was 6% in the younger patients and 4% in the older group, and the incidence of non-fatal reinfarctions was 8% in both groups. Mortality was best predicted by the extent of blood pressure rise (43 +/- 26 mmHg in survivors vs 19 +/- 15 mmHg in non-survivors, P less than 0.001). Stress-test results were no more predictive when non-fatal reinfarction was added to mortality as an end-point. We conclude that for patients in whom the stress test is not contraindicated, age does not affect stress test results, the extent of blood pressure rise during a stress test is the best single predictor of mortality, stress tests are not predictive of reinfarctions.