Prevalence and management of familial hypercholesterolaemia in patients with chest pain admitted to hospital: a retrospective observational study.

OBJECTIVES: Patients with familial hypercholesterolaemia (FH) are genetically burdened by a lifelong elevation of the low-density lipoprotein cholesterol (LDL-C) level, putting them at a very high risk of premature ischaemic heart disease (IHD). This study aims to assess the prevalence of FH among patients admitted for IHD and the preventive treatment status before admission. DESIGN: Observational, retrospective, register-based study. SETTING: Individuals discharged with a diagnosis of IHD were enrolled consecutively throughout 2012-2016 from the cardiac care units of two hospitals in Copenhagen. PARTICIPANTS: 4223 individuals were discharged during the period. Inclusion criteria for further investigation were the availability of one measurement of LDL-C at the time of admission. In total, 2797 individuals were included for further investigation. There were no exclusion criteria. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary objective has been to determine the prevalence of FH in the population. The secondary objective has been to determine the use of lipid-lowering therapy and to which extend the individuals reach their treatment goal. RESULTS: Among the 2797 consecutive patients evaluated, the prevalence of potential FH was 7.7% (1: 13) and 6.8% (1:15) had probably or definite FH. The prevalence of FH was age-dependent: Among the 680 patients (24.3%) with premature IHD (men <55 years/women <60 years), 136 patients (20.0%) had potential FH and 21 (3.1%) had probable/definite FH. None were diagnosed and almost none attained their treatment goal. CONCLUSIONS: There is still a massive lack of recognition of FH in patients admitted to a cardiac care unit with a diagnosis of IHD. Despite a measured high LDL-C, the diagnosis was not made for any patients not even in patients who were admitted at an early age or had a previous cardiovascular event.

Genetic testing increases the likelihood of a diagnosis of familial hypercholesterolaemia among people referred to lipid clinics: Danish national study.

BACKGROUND AND AIMS: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. METHODS: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. RESULTS: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. CONCLUSIONS: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.

Importance of Risk Assessment in Timing of Invasive Coronary Evaluation and Treatment of Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome: Insights From the VERDICT Trial.

Background The optimal timing of invasive examination and treatment of high-risk patients with non-ST-segment-elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard-care invasive coronary angiography on the risk of all-cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non-ST-segment-elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48-72 hours) invasive strategy. The primary outcome of the present study was all-cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow-up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16-3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63-1.10]) (Pinteraction=0.006). Conclusions In patients with non-ST-segment-elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high-risk and low-risk patients with non-ST-segment-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

INTRODUCTION: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. METHODS AND ANALYSIS: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022. ETHICS AND DISSEMINATION: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible. TRIAL REGISTRATION NUMBER: NCT04121949; Pre-results.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Screening for potential familial hypercholesterolaemia in general practice: an observational study on prevalence and management.

BACKGROUND: Familial hypercholesterolaemia (FH) is a common genetic disorder causing premature cardiovascular disease (CVD). The estimated prevalence of probable or definite FH is 1:200-250 individuals, according to the Dutch Lipid Clinic Network (DLCN) criteria for FH. In Denmark approximately 12% of cases are identified. AIM: To provide knowledge of the prevalence and management of FH in general practice. DESIGN & SETTING: A collaboration between six general practice clinics and the department of cardiology at Bispebjerg hospital in Denmark. METHOD: A total of 9652 patient records were screened for hypercholesterolaemia. All patients with a low-density lipoprotein cholesterol (LDL-C) ≥5.0 mmol/l were included in the study population and their records were investigated in order to perform a diagnostic score according to the DLCN criteria. RESULTS: It was found that 2382 individuals had a lipid measurement available, and 236 of those had an LDL-C ≥5.0 mmol/l. In total, 34 individuals were found to have probable or definite FH (DLCN score ≥5). Only three individuals had been diagnosed and treated with lipid-lowering therapy. Of 236 individuals with high LDL-C, only 25 individuals met their treatment target. By excluding patients with signs of secondary hypercholesterolaemia, a subgroup of 115 individuals with potential primary hypercholesterolaemia was established. Among those, 21 individuals were found to have probable or definite FH (1:114 individuals). CONCLUSION: The study shows that there is a massive lack of recognition of FH in general practice. Despite a measured high LDL-C, the diagnosis is rarely made and only a few patients are treated accordingly. Of the patients undergoing treatment, only a few reached their treatment target.

Coronary risk of patients with valvular heart disease: prospective validation of CT-Valve Score.

OBJECTIVE: To prospectively validate the CT-Valve score, a new risk score designed to identify patients with valvular heart disease at a low risk of coronary artery disease (CAD) who could benefit from multislice CT (MSCT) first instead of coronary angiography (CAG). METHODS: This was a prospective cohort study of patients referred for valve surgery in the Capital Region of Denmark and Odense University Hospital from the 1 February 2015 to the 1 February 2017. MSCT was implemented for patients with a CT-Valve score ≤7 at the referring physician's discretion. Patients with a history of CAD or chronic kidney disease were excluded. The primary outcome was the proportion of patients needing reevaluation with CAG after MSCT and risk of CAD among the patients determined to be low to intermediate risk. RESULTS: In total, 1149 patients were included. The median score was 9 (IQR 3) and 339 (30%) had a score ≤7. MSCT was used for 117 patients. Of these 29 (25%) were reevaluated and 9 (7.7%) had CAD. Of the 222 patients with a score ≤7 that did not receive an MSCT, 14 (6%) had significant CAD. The estimated total cost of evaluation among patients with a score ≤7 before implementation was €132 093 compared with €79 073 after, a 40% reduction. Similarly, estimated total radiation before and after was 608 mSv and 362 mSv, a 41% reduction. Follow-up at a median of 32 months (18-48) showed no ischaemic events for patients receiving only MSCT. CONCLUSION: The CT-Valve score is a valid method for determining risk of CAD among patients with valvular heart disease. Using a score ≤7 as a cut-off for the use of MSCT is safe and cost-effective.

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Coronary risk stratification of patients with newly diagnosed heart failure.

Objective: Coronary artery disease (CAD) is frequent in patients with newly diagnosed heart failure (HF). Multislice CT (MSCT) is a non-invasive alternative to coronary angiography (CAG) suggested for patients with a low-to-intermediate risk of CAD. No established definition of such patients exists. Our purpose was to develop a simple score to identify as large a group as possible with a suitable pretest risk of CAD. Methods: Retrospective study of patients in Denmark undergoing CAG due to newly diagnosed HF from 2010 to 2014. All Danish patients were registered in two databases according to geographical location. We used data from one registry and multiple logistic regression with backwards elimination to find predictors of CAD and used the derived OR to develop a clinical risk score called the CT-HF score, which was subsequently validated in the other database. Results: The main cohort consisted of 2171 patients and the validation cohort consisted of 2795 patients with 24% and 27% of patients having significant CAD, respectively. Among significant predictor, the strongest was extracardiac arteriopathy (OR 2.84). Other significant factors were male sex, smoking, hyperlipidaemia, diabetes mellitus, angina and age. A proposed cut-off of 9 points identified 61% of patients with a 15% risk of having CAD, resulting in an estimated savings of 15% of the cost and 21% of the radiation. Conclusions: A simple score based on clinical risk factors could identify HF patients with a low risk of CAD; these patients may have benefitted from MSCT as a gatekeeper for CAG.

Relationship between patient presentation and morphology of coronary atherosclerosis by quantitative multidetector computed tomography.

AIMS: Quantitative computed tomography (QCT) allows assessment of morphological features of coronary atherosclerosis. We aimed to test the hypothesis that clinical patient presentation is associated with distinct morphological features of coronary atherosclerosis. METHODS AND RESULTS: A total of 1652 participants, representing a spectrum of clinical risk profiles [787 asymptomatic individuals from the general population, 468 patients with acute chest pain without acute coronary syndrome (ACS), and 397 patients with acute chest pain and ACS], underwent multidetector computed tomography. Of these, 274 asymptomatic individuals, 254 patients with acute chest pain without ACS, and 327 patients with acute chest pain and ACS underwent QCT to assess coronary plaque volumes and proportions of dense calcium (DC), fibrous, fibro fatty (FF), and necrotic core (NC) tissue. Furthermore, the presence of vulnerable plaques, defined by plaque volume and tissue composition, was examined. Coronary plaque volume increased significantly with worsening clinical risk profile [geometric mean (95% confidence interval): 148 (129-166) mm3, 257 (224-295) mm3, and 407 (363-457) mm3, respectively, P < 0.001]. Plaque composition differed significantly across cohorts, P < 0.0001. The proportion of DC decreased, whereas FF and NC increased with worsening clinical risk profile (mean proportions DC: 33%, 23%, 23%; FF: 50%, 61%, 57%; and NC: 17%, 17%, 20%, respectively). Significant differences in plaque composition persisted after multivariable adjustment for age, gender, body surface area, hypertension, statin use at baseline, diabetes, smoking, family history of ischaemic heart disease, total plaque volume, and tube voltage, P < 0.01. CONCLUSION: Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation.

Prediction of obstructive coronary artery disease and prognosis in patients with suspected stable angina.

AIMS: We hypothesized that the modified Diamond-Forrester (D-F) prediction model overestimates probability of coronary artery disease (CAD). The aim of this study was to update the prediction model based on pre-test information and assess the model's performance in predicting prognosis in an unselected, contemporary population suspected of angina. METHODS AND RESULTS: We included 3903 consecutive patients free of CAD and heart failure and suspected of angina, who were referred to a single centre for assessment in 2012-15. Obstructive CAD was defined from invasive angiography as lesion requiring revascularization, >70% stenosis or fractional flow reserve <0.8. Patients were followed (mean follow-up 33 months) for myocardial infarction, unstable angina, heart failure, stroke, and death. The updated D-F prediction model overestimated probability considerably: mean pre-test probability was 31.4%, while only 274 (7%) were diagnosed with obstructive CAD. A basic prediction model with age, gender, and symptoms demonstrated good discrimination with C-statistics of 0.86 (95% CI 0.84-0.88), while a clinical prediction model adding diabetes, family history, and dyslipidaemia slightly improved the C-statistic to 0.88 (0.86-0.90) (P for difference between models <0.0001). Quartiles of probability of CAD from the clinical prediction model provided good diagnostic and prognostic stratification: in the lowest quartiles there were no cases of obstructive CAD and cumulative risk of the composite endpoint was less than 3% at 2 years. CONCLUSION: The pre-test probability model recommended in current ESC guidelines substantially overestimates likelihood of CAD when applied to a contemporary, unselected, all-comer population. We provide an updated prediction model that identifies subgroups with low likelihood of obstructive CAD and good prognosis in which non-invasive testing may safely be deferred.

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

[Cholesterol-lowering treatment with PCSK9-inhibitors].

Monoclonal antibodies inhibiting proprotein convertase subtilisin-kexin type 9 constitute a new class of lipid-lowering drugs. Currently, evolocumab and alirocumab are marketed. A recent cardiovascular outcome study with evolocumab has shown a cardiovascular (CV) event reduction of 15% in high-risk individuals at very low levels of low-density lipoproteins. The adverse event profile up to two years is mild. Treatment is very costly, and data on CV endpoints are still limited. Treatment is restricted to patients at very high risk of getting CV diseases and on a maximal tolerated statin and ezetimibe treatment in addition to dietary intervention.

Value of Myocardial Perfusion Assessment With Coronary Computed Tomography Angiography in Patients With Recent Acute-Onset Chest Pain.

OBJECTIVES: The authors sought to perform a randomized controlled trial to evaluate the clinical efficacy of combined examination with coronary computed tomography angiography (CTA) and computed tomography perfusion imaging (CTP) compared to coronary CTA alone. BACKGROUND: Stress myocardial CTP may increase diagnostic specificity when added to coronary CTA in patients suspected of having ischemic heart disease. METHODS: Patients recently hospitalized for acute-onset chest pain, who had acute coronary syndrome had been ruled out by normal electrocardiograms, normal troponin levels, and relief of symptoms, and who had a clinical indication for outpatient noninvasive testing, were screened for inclusion in the CATCH-2 (CArdiac cT in the treatment of acute CHest pain 2) trial (NCT02014311). Patients were randomized 1:1 to examination with coronary CTA or coronary CTA+CTP. The primary endpoint was the frequency of coronary revascularization among patients referred for invasive coronary angiography (ICA) based on index computed tomography evaluation. Secondary endpoints were invasive procedural complications at index-related ICA, post-index cardiac death, hospital admittance because of recurrence of chest pain, unstable angina pectoris, or acute myocardial infarction, ICA, and revascularization. RESULTS: Among 300 patients allocated to the coronary CTA+CTP group, 41 (14%) were referred for ICA compared with 89 (30%) allocated to coronary CTA (p < 0.0001). The primary endpoint occurred in 50% of coronary CTA+CTP patients versus 48% of invasively examined patients (p = 0.85). The total number of revascularizations was significantly lower in the coronary CTA+CTP group compared to the coronary CTA group (n = 20 [7%] vs. n = 42 [14%]; p = 0.0045). At median follow-up of 1.5 years, the occurrence of secondary endpoints was similar in the 2 groups. CONCLUSIONS: A post-discharge diagnostic strategy of coronary CTA+CTP safely reduces the need for invasive examination and treatment in patients suspected of having ischemic heart disease. (CArdiac cT in the treatment of acute CHest pain 2-Myocardial CT Perfusion [CATCH2]; NCT02014311).

Low diagnostic yield of non-invasive testing in patients with suspected coronary artery disease: results from a large unselected hospital-based sample.

Aims: Stable angina is the most common presentation of heart disease and has a good prognosis. With declining coronary artery disease (CAD), rates a diagnostic approach balancing costs and benefits is a challenge, particularly in women. This study describes the real-life diagnostic workup in a large hospital to explore whether the diagnostic approach may be improved. Methods and results: We identified 4028 patients free of CAD, referred for and assessed with non-invasive (NIT) or invasive test for stable suspected CAD in 2012-15. In both the sexes, the majority (>85%) presented with chest pain as primary symptom. Women had more non-angina (60.2 vs. 54.5%) and less typical angina (8.2 vs. 11.8%, P < 0.001). Despite a mean pretest probability of 20.9% in women and 45.1% in men (P < 0.001), only 69 (3.1%) women and 190 men (10.4%) were diagnosed with obstructive CAD. In all, 93% underwent a NIT and 80% of these were normal. Among the 1238 men and 1595 women with non-angina or dyspnoea, only 6.1% and 2.9%, respectively, had positive NIT. After multiple adjustments, women remained less likely to have positive NIT [odds ratio (OR) 0.42 95% confidence interval (95% CI 0.32-0.56)] and given a positive test also less likely to have obstructive CAD [OR 0.30 (0.17-0.52)]. The C-statistics for predicting positive NIT was 0.77 (0.72-0.82) in women and 0.77 (0.74-0.80) in men. Conclusion: These data confirm the very low diagnostic yield of non-invasive and invasive assessment of CAD in current clinical practice, particularly in women and in patients with atypical symptoms. Data call for a more rational approach to avoid unnecessary testing.

Coronary risk stratification of patients undergoing surgery for valvular heart disease.

BACKGROUND: Multislice computed tomography (MSCT) is a non-invasive, less expensive, low-radiation alternative to coronary angiography (CAG) prior to valvular heart surgery. MSCT has a high negative predictive value for coronary artery disease (CAD) but previous studies of patients with valvular disease have shown that MSCT, as the primary evaluation technique, lead to re-evaluation with CAG in about a third of cases and it is therefore not recommended. If a subgroup of patients with low- to intermediate risk of CAD could be identified and examined with MSCT, it could be cost-effective, reduce radiation and the risk of complications associated with CAG. METHODS: The study cohort was derived from a national registry of patients undergoing CAG prior to valvular heart surgery. Using logistic regression, we identified significant risk factors for CAD and developed a risk score (CT-valve score). The score was validated on a similar cohort of patients from another registry. RESULTS: The study cohort consisted of 2221 patients, 521 (23.5%) had CAD. The validation cohort consisted of 2575 patients, 771 (29.9%) had CAD. The identified risk factors were male sex, age, smoking, hyperlipidemia, hypertension, aortic valve disease, extracardiac arteriopathy, ejection fraction <30% and diabetes mellitus. CT-valve score could identify a third of the population with a risk about 10%. CONCLUSION: A score based on risk factors of CAD can identify patients that might benefit from using MSCT as a gatekeeper to CAG prior to heart valve surgery.

Myocardial perfusion 320-row multidetector computed tomography-guided treatment strategy for the clinical management of patients with recent acute-onset chest pain: Design of the CArdiac cT in the treatment of acute CHest pain (CATCH)-2 randomized controlled trial.

AIMS: Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP. METHODS: Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded. DISCUSSION: The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain.

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease.

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATERIALS AND METHODS: A total of 242 subjects referred for diagnostic evaluation of possible CAD had blood samples obtained before, 5 min after, and again 20 h after a symptom-limited exercise test. RESULTS: Totally 40 subjects had CAD with ≥ 50% stenosis, 115 subjects had no stenosis and 87 subjects served as controls. In univariate analysis CAD-subjects had higher median baseline NT-pro-BNP-levels (85.3 ng/L) compared with non-CAD-subjects (41.3 ng/L) and controls (40.1 ng/L), both p < 0.001, but the association disappeared in multivariate analysis adjusted for age and gender. NT-pro-BNP increased similarly after exercise in CAD-subjects, non-CAD-subjects, and controls (median increase 8.14 ng/L) and the increase was positively associated with baseline NT-pro-BNP but not presence of CAD. Median baseline cTnT was 6.25 ng/L in CAD-subjects and 3.00 ng/L in non-CAD-subjects as well as controls, both p < 0.0001. Median ΔcTnT (baseline to 20 h after exercise) was higher in CAD-subjects than non-CAD-subjects and controls (0.62 ng/L vs. 0.0 ng/L, p < 0.001). A linear relationship between ΔcTnT and 'percent of predicted maximal heart rate achieved' was found in subjects with ≥ 70% stenosis (n = 24, r = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP.

Level of education and risk of heart failure: a prospective cohort study with echocardiography evaluation.

AIMS: With increasing socioeconomic disparity in cardiovascular risk factors, there is a need to assess the role of socioeconomic factors in chronic heart failure (CHF) and to what extent this is caused by modifiable risk factors. METHODS AND RESULTS: In a prospective cohort of 18 616 men and women without known myocardial infarction or CHF examined in 1976-78, 1981-83, 1991-94, and 2001-03 in the Copenhagen City Heart Study, we studied the effect of education on CHF incidence. During a median follow-up of 21 years (range 0-31), 2190 participants were admitted to hospital for CHF. Age-adjusted hazard ratio (HR) for intermediary (8-10 years) and high level of education (>10 years) with low (< 8 years) as reference was 0.69 (0.62-0.78) and 0.52 (0.43-0.63), respectively, with similar associations in men and women. After adjusting for updated cardiovascular risk factors, corresponding HRs were 0.75 (0.67-0.85) and 0.61 (0.50-0.73). In a random subset of the population examined with echocardiography in 2001-03 (n = 3589), education was associated with left ventricular (LV) hypertrophy, LV dilatation, reduced LV ejection fraction, and severe diastolic dysfunction (P for trend, all <0.05), whereas no association was found for mild diastolic dysfunction (P for trend, 0.61). With the exception of LV hypertrophy, significant associations persisted after adjustment for potential mediating factors. CONCLUSION: In this cohort study, the level of education was associated with cardiac dysfunction and predicted future hospital admission for CHF. Only a minor part of the excess risk was mediated through traditional cardiovascular risk factors. Strategies to reduce this inequality should be strengthened.