Characteristics, Treatment Strategies and Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction: A Contemporary Dutch Cohort.

Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high morbidity and mortality. Our study aimed to gain insights into patient characteristics, outcomes and treatment strategies in CS patients. Patients with CS who underwent percutaneous coronary intervention (PCI) between 2017 and 2021 were identified in a nationwide registry. Data on medical history, laboratory values, angiographic features and outcomes were retrospectively assessed. A total of 2328 patients with a mean age of 66 years and of whom 73% were male, were included. Mortality at 30 days was 39% for the entire cohort. Non-survivors presented with a lower mean blood pressure and increased heart rate, blood lactate and blood glucose levels (p-value for all <0.001). Also, an increased prevalence of diabetes, multivessel coronary artery disease and a prior coronary event were found. Of all patients, 24% received mechanical circulatory support, of which the majority was via intra-aortic balloon pumps (IABPs). Furthermore, 79% of patients were treated with at least one vasoactive agent, and multivessel PCI was performed in 28%. In conclusion, a large set of hemodynamic, biochemical and patient-related characteristics was identified to be associated with mortality. Interestingly, multivessel PCI and IABPs were frequently applied despite a lack of evidence.

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Development and Internal Validation of a Practical Model to Identify Observe Patients of the European Society of Cardiology 0/1-h Algorithm at Low Risk of a Coronary Diagnosis.

BACKGROUND: Patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) assigned to the "observe" zone of the European Society of Cardiology (ESC) 0/1-h algorithm form a heterogeneous group known to have an unfavourable prognosis. We aim to elucidate the clinical characteristics and management of these patients and generate a model that is predictive of a coronary diagnosis at index visit to the emergency department (ED). METHODS: A retrospective observational cohort study, including adult patients presenting to the ED with suspected NSTE-ACS assigned to the "observe" zone of the ESC 0/1-h algorithm. Multivariable logistic regression analysis was performed for the prediction of a coronary diagnosis. Internal validation was performed using bootstrap resampling. RESULTS: A total of 750 patients were included; mean age 66 ± 13 years, 35% women, 50% with prior history of coronary artery disease (CAD). In 372 (50%) patients a diagnosis was established within 30 days of index presentation, of whom 169 (45%) patients had a coronary-related event. Multivariable logistic regression analysis generated a 12-point risk score incorporating 5 variables for the prediction of such event, including type of angina, chest pain occurring during inspiration, prior history of CAD, ST-segment deviation on electrocardiogram, and estimated glomerular filtration rate <60. The final model had an optimism-corrected c-statistic of 0.78 (95% confidence interval [CI]: 0.74-0.82). A score <6 ruled out a coronary event in 276 (37%) patients, with a sensitivity and negative predictive value of 90% (95% CI: 84-94) and 94% (91-96), respectively. CONCLUSION: A score <6 identifies patients at low risk of a coronary diagnosis and can guide clinical decision-making in choosing the appropriate diagnostic test.

Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease.

OBJECTIVES: In this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR). BACKGROUND: CT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies. METHODS: At 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics. RESULTS: ICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively. CONCLUSIONS: Dynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795).

Coronary CT angiography for improved assessment of patients with acute chest pain and low-range positive high-sensitivity troponins: study protocol for a prospective, observational, multicentre study (COURSE trial).

INTRODUCTION: Current evaluation of patients suspected of a non-ST-elevation acute coronary syndrome (NSTE-ACS) involves the use of algorithms that incorporate clinical information, electrocardiogram (ECG) and high-sensitivity cardiac troponins (hs-troponins). While primarily designed to rule out NSTE-ACS safely, these algorithms can also be used for rule in of NSTE-ACS in some patients. Still, in a substantial number of patients, these algorithms do not provide a conclusive work-up. These patients often present with an atypical clinical profile and low-range positive hs-troponin values without a characteristic rise or fall pattern. They represent a heterogeneous group of patients with various underlying conditions; only a fraction (30%-40%) will eventually be diagnosed with a myocardial infarction. Uncertainty exists about the optimal diagnostic strategy and their management depends on the clinical perspective of the treating physician ranging from direct discharge to admission for invasive coronary angiography. Coronary CT angiography (CCTA) is a non-invasive test that has been shown to be safe, fast and reliable in the evaluation of coronary artery disease. In this study, we will determine the usefulness of CCTA in patients with acute chest pain and low-range positive hs-troponin values. METHODS AND ANALYSIS: A prospective, double-blind, observational, multicentre study conducted in the Netherlands. Patients aged 30-80 years presenting to the emergency department with acute chest pain and a suspicion of NSTE-ACS, a normal or non-diagnostic ECG and low-range positive hs-troponins will be scheduled to undergo CCTA. The primary outcome is the diagnostic accuracy of CCTA for the diagnosis of NSTE-ACS at discharge, in terms of sensitivity and negative predictive value. ETHICS AND DISSEMINATION: This study was approved by the Medical Research Ethics Committee of Erasmus Medical Center in Rotterdam, the Netherlands (registration number MEC-2017-506). Written informed consent to participate will be obtained from all participants. This study's findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03129659).

Undetectable High-Sensitivity Troponin T as a Gatekeeper for Coronary Computed Tomography Angiography in Patients Suspected of Acute Coronary Syndrome.

OBJECTIVES: The aim of this study was to characterize the safety and efficiency of a strategy employing the limit of detection (LoD) of high-sensitivity troponin T (hs-TnT) as a gatekeeper for coronary computed tomography angiography (CCTA) in suspected acute coronary syndrome (ACS) patients in the emergency department (ED). METHODS: We included suspected ACS patients who underwent CCTA and were evaluated with hs-TnT. Patients were categorized as below the LoD and at or above the LoD. The primary outcome was 30-day major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or coronary revascularization. RESULTS: The study population consisted of 177 patients (mean age 55 ± 10 years, 50.3% women), and 16 (9.0%) patients reached the primary outcome. None of the patients died, while 13 had an adjudicated diagnosis of ACS, and 3 underwent elective coronary revascularization. There were 77 patients (44%) with an hs-TnT value below the LoD (MACEs; n = 1 [1.3%]) and 100 (56%) with at or above the LoD levels (MACEs; n = 15 [15%]). None of 67 patients with an hs-TnT value below the LoD and <50% stenosis on CCTA experienced MACEs. Out of the 10 patients with an hs-TnT value below the LoD and ≥50% stenosis on CCTA, 1 patient underwent elective percutaneous coronary revascularization. In patients with an hs-TnT value at or above the LoD, 74 patients had <50% stenosis on CCTA, and 2 patients (3%) were diagnosed with myocardial infarction without obstructive coronary artery disease confirmed on invasive angiography. Thirteen (50%) patients with an hs-TnT value at or above the LoD and ≥50% stenosis on CCTA experienced MACEs (11 ACS and 2 elective percutaneous coronary revascularizations). CONCLUSION: Our findings support that implementing the LoD of hs-TnT as a gatekeeper may reduce the need for CCTA in suspected ACS patients in the ED.

Pressure-Volume Loop Analysis in Percutaneous Coronary Intervention-Induced Shock.

High-risk percutaneous coronary intervention may lead to undesirable clinical scenarios such as cardiogenic shock. We describe the hemodynamic changes using pressure-volume loop analyses in percutaneous coronary intervention-induced shock. (PULsecath mechanicaL Support Evaluation [PULSE]; NCT03200990) (Level of Difficulty: Intermediate.).

HEART score improves efficiency of coronary computed tomography angiography in patients suspected of acute coronary syndrome in the emergency department.

AIMS: Coronary computed tomography angiography is increasingly employed in the emergency department for suspected acute coronary syndrome patients. The HEART score has been proposed for initial risk stratification in these patients. The aim of this study was to investigate the diagnostic value and efficiency of the HEART score before coronary computed tomography angiography. METHODS AND RESULTS: We included patients suspected of acute coronary syndrome who underwent coronary computed tomography angiography in the emergency department. Based on the HEART score, patients were stratified as low-risk (HEART≤3), intermediate-risk (HEART4-6) and high-risk (HEART≥7). We assessed coronary computed tomography angiography for the presence of significant coronary artery disease (>50% stenosis). The primary outcome, the level of major adverse cardiac events, was a composite endpoint of all-cause mortality, acute coronary syndrome or coronary revascularisation within 30 days. The study population consisted of 340 patients (mean age: 55.6±10.1 years, 44.7% women), major adverse cardiac events occurred in 45 (13.2%) patients. The incidence of major adverse cardiac events in patients stratified as low-risk (35.0%), intermediate-risk (56.8%) and high-risk (8.2%) was 3.4%, 12.4% and 60.7%, respectively. All four low-risk patients with major adverse cardiac events had a HEART score of three. An algorithm where coronary computed tomography angiography is reserved for patients with HEART 3-6 resulted in a sensitivity of 97.8%, specificity of 84.1%, negative predictive value of 99.6% and positive predictive value of 48.4%, while reducing the need for coronary computed tomography angiography by 22% (n=75). CONCLUSION: The predictive value of coronary computed tomography angiography for 30-day major adverse cardiac events in suspected acute coronary syndrome patients is good, and reserving coronary computed tomography angiography for HEART score 3-6 patients reduces the number of needed coronary computed tomography angiograms without affecting diagnostic accuracy.

Round-the-clock performance of coronary CT angiography for suspected acute coronary syndrome: Results from the BEACON trial.

OBJECTIVE: To assess the image quality of coronary CT angiography (CCTA) for suspected acute coronary syndrome (ACS) outside office hours. METHODS: Patients with symptoms suggestive of an ACS underwent CCTA at the emergency department 24 hours, 7 days a week. A total of 118 patients, of whom 89 (75 %) presented during office hours (weekdays between 07:00 and 17:00) and 29 (25 %) outside office hours (weekdays between 17:00 and 07:00, weekends and holidays) underwent CCTA. Image quality was evaluated per coronary segment by two experienced readers and graded on an ordinal scale ranging from 1 to 3. RESULTS: There were no significant differences in acquisition parameters, beta-blocker administration or heart rate between patients presenting during office hours and outside office hours. The median quality score per patient was 30.5 [interquartile range 26.0-33.5] for patients presenting during office hours in comparison to 27.5 [19.75-32.0] for patients presenting outside office hours (p=0.043). The number of non-evaluable segments was lower for patients presenting during office hours (0 [0-1.0] vs. 1.0 [0-4.0], p=0.009). CONCLUSION: Image quality of CCTA outside office hours in the diagnosis of suspected ACS is diminished. KEY POINTS: • Quality scores were higher for coronary-CTA during office hours. • There were no differences in acquisition parameters. • There was a non-significant trend towards higher heart rates outside office hours. • Coronary-CTA on the ED requires state-of-the-art scanner technology and sufficiently trained staff. • Coronary-CTA on the ED needs preparation time and optimisation of the procedure.

Sex Differences in the Performance of Cardiac Computed Tomography Compared With Functional Testing in Evaluating Stable Chest Pain: Subanalysis of the Multicenter, Randomized CRESCENT Trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease).

BACKGROUND: Cardiac computed tomography (CT) represents an alternative diagnostic strategy for women with suspected coronary artery disease, with potential benefits in terms of effectiveness and cost-efficiency. METHODS AND RESULTS: The CRESCENT trial (Calcium Imaging and Selective CT Angiography in Comparison to Functional Testing for Suspected Coronary Artery Disease) prospectively randomized 350 patients with stable angina (55% women; aged 55±10 years), mostly with an intermediate coronary artery disease probability, between cardiac CT and functional testing. The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. Sex differences were studied as a prespecified subanalysis. Enrolled women presented more frequently with atypical chest pain and had a lower pretest probability of coronary artery disease compared with men. Independently of these differences, cardiac CT led in both sexes to a fast final diagnosis when compared with functional testing, although the effect was larger in women (P interaction=0.01). The reduced need for further testing after CT, compared with functional testing, was most evident in women (P interaction=0.009). However, no sex interaction was observed with respect to changes in angina and quality of life, cumulative diagnostic costs, and applied radiation dose (all P interactions≥0.097). CONCLUSIONS: Cardiac CT is more efficient in women than in men in terms of time to reach the final diagnosis and downstream testing. However, overall clinical outcome showed no significant difference between women and men after 1 year. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01393028.

Is there still a role for cardiac CT in the emergency department in the era of highly-sensitive troponins?

Physicians practicing cardiovascular medicine are every day confronted with patients presenting with symptoms suggestive of an acute coronary syndrome (ACS). Over the years, there have been substantial technical advances, such as the introduction of new non-invasive imaging techniques and the introduction of new highly sensitive cardiac biomarkers. Physicians have adopted these new assets and have become more experienced with them thus improving medical care. Nevertheless, the search for an efficient, yet safe diagnostic work-up for patients presenting with symptoms suggestive of ACS is ongoing. A large proportion of patients will require some form of non-invasive testing and the choice for the diagnostic modality as well as its timing are important steps in this process. Cardiac computed tomography (CT), a non-invasive imaging technique that rapidly provides visualization of the coronary artery tree, is an attractive option, with its unparalleled negative predictive value for obstructive coronary artery disease (CAD). With the introduction of highly-sensitive troponins (hsTn), the role of non-invasive testing, including cardiac CT, has changed. This review will provide an oversight on what is known about cardiac CT in acute chest presentations. Furthermore, we will discuss the changing role of cardiac CT in the era of hsTn and the possibility of their combined use in the work-up of suspected ACS patients. hsTn is currently an established tool for the diagnosis and triage of patients with suspected ACS. The role of cardiac CT has shifted now to a secondary, comprehensive rule-out test in patients with inconclusive biomarker status, providing information on stenosis severity, plaque burden, high-risk features and the presence of other serious conditions that can also give rise to hsTn.

Diagnostic value of transmural perfusion ratio derived from dynamic CT-based myocardial perfusion imaging for the detection of haemodynamically relevant coronary artery stenosis.

OBJECTIVES: To investigate the additional value of transmural perfusion ratio (TPR) in dynamic CT myocardial perfusion imaging for detection of haemodynamically significant coronary artery disease compared with fractional flow reserve (FFR). METHODS: Subjects with suspected or known coronary artery disease were prospectively included and underwent a CT-MPI examination. From the CT-MPI time-point data absolute myocardial blood flow (MBF) values were temporally resolved using a hybrid deconvolution model. An absolute MBF value was measured in the suspected perfusion defect. TPR was defined as the ratio between the subendocardial and subepicardial MBF. TPR and MBF results were compared with invasive FFR using a threshold of 0.80. RESULTS: Forty-three patients and 94 territories were analysed. The area under the receiver operator curve was larger for MBF (0.78) compared with TPR (0.65, P = 0.026). No significant differences were found in diagnostic classification between MBF and TPR with a territory-based accuracy of 77 % (67-86 %) for MBF compared with 70 % (60-81 %) for TPR. Combined MBF and TPR classification did not improve the diagnostic classification. CONCLUSIONS: Dynamic CT-MPI-based transmural perfusion ratio predicts haemodynamically significant coronary artery disease. However, diagnostic performance of dynamic CT-MPI-derived TPR is inferior to quantified MBF and has limited incremental value. KEY POINTS: • The transmural perfusion ratio from dynamic CT-MPI predicts functional obstructive coronary artery disease • Performance of the transmural perfusion ratio is inferior to quantified myocardial blood flow • The incremental value of the transmural perfusion ratio is limited.

[Coronary artery calcium score in clinical practice]. / De coronaire calciumscore in de klinische praktijk.

Since the beginning of the 1990s it is possible to obtain images of the heart using CT technology to visualise coronary calcifications. The amount of coronary calcification can be quantified with a coronary artery calcium score. Today, there is sufficient scientific evidence that justifies the use of the coronary artery calcium score in selected patients. In asymptomatic patients, the coronary artery calcium score can be used for more precise and tailored risk stratification for the occurrence of future cardiovascular events. The absence of coronary calcification is associated with a good prognosis. In addition, the coronary artery calcium score can also be used as the initial test in symptomatic patients, to dictate treatment strategies going forward.

Prognostic Value of Coronary Computed Tomography Imaging in Patients at High Risk Without Symptoms of Coronary Artery Disease.

At present, traditional risk factors are used to guide cardiovascular management of asymptomatic subjects. Intensified surveillance may be warranted in those identified as high risk of developing cardiovascular disease (CVD). This study aims to determine the prognostic value of coronary computed tomography (CT) angiography (CCTA) next to the coronary artery calcium score (CACS) in patients at high CVD risk without symptoms suspect for coronary artery disease (CAD). A total of 665 patients at high risk (mean age 56 ± 9 years, 417 men), having at least one important CVD risk factor (diabetes mellitus, familial hypercholesterolemia, peripheral artery disease, or severe hypertension) or a calculated European systematic coronary risk evaluation of >10% were included from outpatient clinics at 2 academic centers. Follow-up was performed for the occurrence of adverse events including all-cause mortality, nonfatal myocardial infarction, unstable angina, or coronary revascularization. During a median follow-up of 3.0 (interquartile range 1.3 to 4.1) years, adverse events occurred in 40 subjects (6.0%). By multivariate analysis, adjusted for age, gender, and CACS, obstructive CAD on CCTA (≥50% luminal stenosis) was a significant predictor of adverse events (hazard ratio 5.9 [CI 1.3 to 26.1]). Addition of CCTA to age, gender, plus CACS, increased the C statistic from 0.81 to 0.84 and resulted in a total net reclassification index of 0.19 (p <0.01). In conclusion, CCTA has incremental prognostic value and risk reclassification benefit beyond CACS in patients without CAD symptoms but with high risk of developing CVD.

Coronary CT angiography derived fractional flow reserve: Methodology and evaluation of a point of care algorithm.

BACKGROUND: Recently several publications described the diagnostic value of coronary CT angiography (coronary CTA) derived fractional flow reserve (CTA-FFR). For a recently introduced on-site CTA-FFR application, detailed methodology and factors potentially affecting performance have not yet been described. OBJECTIVE: To provide a methodological background for an on-site CTA-FFR application and evaluate the effect of patient and acquisition characteristics. METHODS: The on-site CTA-FFR application utilized a reduced-order hybrid model applying pressure drop models within stenotic regions. In 116 patients and 203 vessels the diagnostic performance of CTA-FFR was investigated using invasive FFR measurements as a reference. The effect of several potentially relevant factors on CTA-FFR was investigated. RESULTS: 90 vessels (44%) had a hemodynamically relevant stenosis according to invasive FFR (threshold ≤0.80). The overall vessel-based sensitivity, specificity and accuracy of CTA-FFR were 88% (CI 95%:79-94%), 65% (55-73%) and 75% (69-81%). The specificity was significantly lower in the presence of misalignment artifacts (25%, CI: 6-57%). A non-significant reduction in specificity from 74% (60-85%) to 48% (26-70%) was found for higher coronary artery calcium scores. Left ventricular mass, diabetes mellitus and large vessel size increased the discrepancy between invasive FFR and CTA-FFR values. CONCLUSIONS: On-site calculation of CTA-FFR can identify hemodynamically significant CAD with an overall per-vessel accuracy of 75% in comparison to invasive FFR. The diagnostic performance of CTA-FFR is negatively affected by misalignment artifacts. CTA-FFR is potentially affected by left ventricular mass, diabetes mellitus and vessel size.

Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial.

AIMS: To compare the effectiveness and safety of a cardiac computed tomography (CT) algorithm with functional testing in patients with symptoms suggestive of coronary artery disease (CAD). METHODS AND RESULTS: Between April 2011 and July 2013, 350 patients with stable angina, referred to the outpatient clinic of four Dutch hospitals, were prospectively randomized between cardiac CT and functional testing (2 : 1 ratio). The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. By 1 year, fewer patients randomized to cardiac CT reported anginal complaints (P = 0.012). The cumulative radiation dose was slightly higher in the CT group (6.6 ± 8.7 vs. 6.1 ± 9.3 mSv; P < 0.0001). After 1.2 years, event-free survival was 96.7% for patients randomized to CT and 89.8% for patients randomized to functional testing (P = 0.011). After CT, the final diagnosis was established sooner (P < 0.0001), and additional downstream testing was required less frequently (25 vs. 53%, P < 0.0001), resulting in lower cumulative diagnostic costs (€369 vs. €440; P < 0.0001). CONCLUSION: For patients with suspected stable CAD, a tiered cardiac CT protocol offers an effective and safe alternative to functional testing. Incorporating the calcium scan into the diagnostic workup was safe and lowered diagnostic expenses and radiation exposure.

Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study.

BACKGROUND: It is uncertain whether a diagnostic strategy supplemented by early coronary computed tomography angiography (CCTA) is superior to contemporary standard optimal care (SOC) encompassing high-sensitivity troponin assays (hs-troponins) for patients suspected of acute coronary syndrome (ACS) in the emergency department (ED). OBJECTIVES: This study assessed whether a diagnostic strategy supplemented by early CCTA improves clinical effectiveness compared with contemporary SOC. METHODS: In a prospective, open-label, multicenter, randomized trial, we enrolled patients presenting with symptoms suggestive of an ACS at the ED of 5 community and 2 university hospitals in the Netherlands. Exclusion criteria included the need for urgent cardiac catheterization and history of ACS or coronary revascularization. The primary endpoint was the number of patients identified with significant coronary artery disease requiring revascularization within 30 days. RESULTS: The study population consisted of 500 patients, of whom 236 (47%) were women (mean age 54 ± 10 years). There was no difference in the primary endpoint (22 [9%] patients underwent coronary revascularization within 30 days in the CCTA group and 17 [7%] in the SOC group [p = 0.40]). Discharge from the ED was not more frequent after CCTA (65% vs. 59%, p = 0.16), and length of stay was similar (6.3 h in both groups; p = 0.80). The CCTA group had lower direct medical costs (€337 vs. €511, p < 0.01) and less outpatient testing after the index ED visit (10 [4%] vs. 26 [10%], p < 0.01). There was no difference in incidence of undetected ACS. CONCLUSIONS: CCTA, applied early in the work-up of suspected ACS, is safe and associated with less outpatient testing and lower costs. However, in the era of hs-troponins, CCTA does not identify more patients with significant CAD requiring coronary revascularization, shorten hospital stay, or allow for more direct discharge from the ED. (Better Evaluation of Acute Chest Pain with Computed Tomography Angiography [BEACON]; NCT01413282).

Increased Aortic Valve Calcification in Familial Hypercholesterolemia: Prevalence, Extent, and Associated Risk Factors.

BACKGROUND: Familial hypercholesterolemia is typically caused by LDL receptor (LDLR) mutations that result in elevated levels of LDL cholesterol (LDL-C). In homozygous FH, the prevalence of aortic valve calcification (AoVC) reaches 100% and is often symptomatic. OBJECTIVES: The objective of this study was to investigate the prevalence, extent, and risk-modifiers of AoVC in heterozygous FH (he-FH) that are presently unknown. METHODS: Asymptomatic patients with he-FH and 131 non-familial hypercholesterolemia controls underwent CT computed tomography calcium scoring. AoVC was defined as the presence of calcium at the aortic valve leaflets. The extent of AoVC was expressed in Agatston units, as the AoVC-score. We compared the prevalence and extent of AoVC between cases and controls. In addition, we investigated risk modifiers of AoVC, including the presence of LDLR mutations without residual function (LDLR-negative mutations), maximum untreated LDL-cholesterol (maxLDL), LDL-C, blood pressure, and coronary artery calcification (CAC). RESULTS: We included 145 asymptomatic patients with he-FH (93 men; mean age 52 ± 8 years) and 131 non-familial hypercholesterolemia controls. The prevalence (%) and AoVC-score (median, IQR) were higher in he-FH patients than in controls: 41%, 51 (9-117); and 21%, 21 (3-49) (p < 0.001 and p = 0.007). Age, untreated maxLDL, CAC, and diastolic blood pressure were independently associated with AoVC. LDLR-negative mutational he-FH was the strongest predictor of the AoVC-score (OR: 4.81; 95% CI: 2.22 to 10.40; p = <0.001). CONCLUSIONS: Compared to controls, he-FH is associated with a high prevalence and a large extent of subclinical AoVC, especially in patients with LDLR-negative mutations, highlighting the critical role of LDL-C metabolism in AoVC etiology.

Fractional flow reserve computed from noninvasive CT angiography data: diagnostic performance of an on-site clinician-operated computational fluid dynamics algorithm.

PURPOSE: To validate an on-site algorithm for computation of fractional flow reserve (FFR) from coronary computed tomographic (CT) angiography data against invasively measured FFR and to test its diagnostic performance as compared with that of coronary CT angiography. MATERIALS AND METHODS: The institutional review board provided a waiver for this retrospective study. From coronary CT angiography data in 106 patients, FFR was computed at a local workstation by using a computational fluid dynamics algorithm. Invasive FFR measurement was performed in 189 vessels (80 of which had an FFR ≤ 0.80); these measurements were regarded as the reference standard. The diagnostic characteristics of coronary CT angiography-derived computational FFR, coronary CT angiography, and quantitative coronary angiography were evaluated against those of invasively measured FFR by using C statistics. Sensitivity and specificity were compared by using a two-sided McNemar test. RESULTS: For computational FFR, sensitivity was 87.5% (95% confidence interval [CI]: 78.2%, 93.8%), specificity was 65.1% (95% CI: 55.4%, 74.0%), and accuracy was 74.6% (95% CI: 68.4%, 80.8%), as compared with the finding of lumen stenosis of 50% or greater at coronary CT angiography, for which sensitivity was 81.3% (95% CI: 71.0%, 89.1%), specificity was 37.6% (95% CI: 28.5%, 47.4%), and accuracy was 56.1% (95% CI: 49.0%, 63.2%). C statistics revealed a larger area under the receiver operating characteristic curve (AUC) for computational FFR (AUC, 0.83) than for coronary CT angiography (AUC, 0.64). For vessels with intermediate (25%-69%) stenosis, the sensitivity of computational FFR was 87.3% (95% CI: 76.5%, 94.3%) and the specificity was 59.3% (95% CI: 47.8%, 70.1%). CONCLUSION: With use of a reduced-order algorithm, computation of the FFR from coronary CT angiography data can be performed locally, at a regular workstation. The diagnostic accuracy of coronary CT angiography-derived computational FFR for the detection of functionally important coronary artery disease (CAD) was good and was incremental to that of coronary CT angiography within a population with a high prevalence of CAD.