The consistency of the treatment effect of an ACE-inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease: A combined analysis of individual data of ADVANCE, EUROPA, and PROGRESS trials

AimsAngiotensin-converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk in different groups of patients. Whether these effects can be generalized to the broad group of patients with vascular disease is unknown. Therefore, we undertook a combined analysis using individual data from ADVANCE, EUROPA, and PROGRESS to determine the consistency of the treatment effect of perindopril-based regimen in patients with vascular disease or at high risk of vascular disease.Methods and resultsWe studied all-cause mortality and major cardiovascular outcomes during a follow-up of about 4 years in the 29 463 patients randomly assigned a perindopril-based treatment regimen or placebo. The perindopril-based regimens were associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.89; 95 confidence interval (CI) 0.82-0.96; P = 0.006], cardiovascular mortality (HR 0.85; 95 CI 0.76-0.95; P = 0.004), non-fatal myocardial infarction (HR 0.80; 95 CI 0.71-0.90; P < 0.001), stroke (HR 0.82; 95 CI 0.74-0.92; P = 0.002), and heart failure (HR 0.84; 95 CI 0.72-0.96; P = 0.015). Results were consistent in subgroups with different clinical characteristics, concomitant medication use, and across all strata of baseline blood pressure.ConclusionThis study provides strong evidence for a consistent cardiovascular protection with an ACE-inhibitor treatment regimen (perindopril-indapamide) by improving survival and reducing the risk of major cardiovascular events across a broad spectrum of patients with vascular disease

Multicentre reference values for cardiac magnetic resonance imaging derived ventricular size and function for children aged 0-18 years

AIMS: Cardiovascular magnetic resonance (CMR) imaging is an important tool in the assessment of paediatric cardiac disease. Reported reference values of ventricular volumes and masses in the paediatric population are based on small cohorts and several methodologic differences between studies exist. We sought to create steady-state free precession (SSFP) CMR reference values for biventricular volumes and mass by combining data of previously published studies and re-analysing these data in a standardized manner. METHODS AND RESULTS: A total of 141 healthy children (68 boys) from three European centres underwent cine-SSFP CMR imaging. Cardiac structures were manually contoured for end-diastolic and end-systolic phases in the short-axis orientation according to current standardized CMR post-processing guidelines. Volumes and masses were derived from these contours. Age-related reference curves were constructed using the lambda mu sigma method. Median age was 12.7 years (range 0.6-18.5). We report biventricular volumes and masses, unindexed and indexed for body surface area, stratified by age groups. In general, boys had approximately 15% higher biventricular volumes and masses compared with girls. Only in children aged <6 years old no gender differences could be observed. Left ventricle ejection fraction was slightly higher in boys in this study population (median 67% vs. 65%, P = 0.016). Age-related reference curves showed non-linear relations between age and cardiac parameters. CONCLUSION: We report volumetric SSFP CMR imaging reference values for children aged 0-18 years old in a relatively large multi-centre cohort. These references can be used in the follow-up of paedi

Does Repeated Measurement of a 6-Min Walk Test Contribute to Risk Prediction in Children with Dilated Cardiomyopathy?

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients >= 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2-6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5-5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86-0.95 p <0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test

Individualized angiotensin-converting enzyme (ACE)-inhibitor therapy in stable coronary artery disease based on clinical and pharmacogenetic determinants: The PERindopril GENEtic (PERGENE) risk model

Background-Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. Methods and Results-Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 t

Suradnja geodeta sa sudskim vještacima građevinske struke u postupku legalizacije objekata izgrađenih prije 15. veljače 1968. godine

U radu je opisana važnost prilaganja uporabne dozvole prilikom upisa objekata u zemljišne knjige. Iz novog zakona o državnoj izmjeri i katastru nekretnina (»Narodne novine«, broj 16/07) moguće je zaključiti kako će i katastarskim uredima građevna dokumentacija predstavljati važnu ulogu prilikom ovjere geodetskih elaborata upisa građevina. Detaljno je opisan postupak interakcije građevinskih vještaka sa geodetima prilikom evidentiranja građevina koje su izgrađene prije 15.veljače 1968., a nisu evidentirane u službenoj dokumentaciji Državne geodetske uprave. U radu su navedeni i sastavni dijelovi geodestkih elaborata kao i sastavni dijelovi elaborata o utvrđivanju starosti građevina

Diagnostic performance of exercise bicycle testing and single-photon emission computed tomography: Comparison with 64-slice computed tomography coronary angiography

To conduct a comparison of the diagnostic performance of exercise bicycle testing and singlephoton emission computed tomography (SPECT) with computed tomography coronary angiography (CTCA) for the detection of obstructive coronary artery disease (CAD) in patients with stable angina. 376 symptomatic patients (254 men, 122 women, mean age 60.4 ± 10.0 years) referred for noninvasive stress testing (exercise bicycle test and/or SPECT) and invasive coronary angiography were included. All patients underwent additional 64-slice CTCA. The diagnostic performance of exercise bicycle testing (ST segment depression), SPECT (reversible perfusion defect) and CTCA (≥50% lumen diameter reduction) was presented as sensitivity, specificity, positive and negative predictive value (PPV and NPV) to detect or rule out obstructive CAD with quantitative coronary angiography as reference standard. Comparisons of exercise bicycle testing versus CTCA (n = 334), and SPECT versus CTCA (n = 61) were performed. The diagnostic performance of exercise bicycle testing was significantly (P value0.05): 77% (95% CI, 50-92) vs. 82% (95% CI, 56-95). We observed a PPV of 91% (95% CI, 77-97) vs. 93% (95% CI, 81-98); andNPVof 72% (95%, 46-89) vs. 93% (95%, 66-100). SPECT and CTCA yielded higher diagnostic performance compared to traditional exercise bicycle testing for the detection and rule out of obstructive CAD in patients with stable angina

Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction:Results from the POPular Genetics Trial

INTRODUCTION: The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI). OBJECTIVE: In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel. METHODS: A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies). RESULTS: Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant. CONCLUSION: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872

Computed tomography coronary angiography accuracy in women and men at low to intermediate risk of coronary artery disease

Objectives To investigate the diagnostic accuracy of CT coronary angiography (CTCA) in women at low to intermediate pre-test probability of coronary artery disease (CAD) compared with men. Methods In this retrospective study we included symptomatic patients with low to intermediate risk who underwent both invasive coronary angiography and CTCA. Exclusion criteria were previous revascularisation or myocardial infarction. The pre-test probability of CAD was estimated using the Duke risk score. Thresholds of less than 30 % and 30-90 % were used for determining low and intermediate risk, respectively. The diagnostic accuracy of CTCA in detecting obstructive CAD (≥50 % lumen diameter narrowing) was calculated on patient level. P<0.05 was considered significant. Results A total of 570 patients (46 % women [262/570]) were included and stratified as low (women 73 % [80/109]) and intermediate risk (women 39 % [182/461]). Sensitivity, specificity, PPV and NPV were not significantly different in and between women and men at low and intermediate risk. For women vs. me

Does Repeated Measurement of a 6-Min Walk Test Contribute to Risk Prediction in Children with Dilated Cardiomyopathy?

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM