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.

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.

Prognostic implications of non-culprit plaques in acute coronary syndrome: non-invasive assessment with coronary CT angiography.

AIMS: Non-culprit plaques are responsible for a substantial number of future events in patients with acute coronary syndrome (ACS). In this study, we evaluated the prognostic implications of non-culprit plaques seen on coronary computed tomography angiography (CTA) in patients with ACS. METHODS AND RESULTS: Coronary CTA was performed in 169 patients (mean 59 ± 11 years, 129 males) admitted with ACS. Data sets were assessed for the presence of obstructive non-culprit plaques (>50% luminal narrowing), segment involvement score, and quantitative measures of plaque burden, after censoring initial culprit plaques. Follow-up was performed for the occurrence of major adverse cardiovascular events (MACEs) unrelated to the initial culprit plaque; cardiac death, second ACS, or coronary revascularization after 90 days. After a median follow-up of 4.8 (IQR 2.6-6.6) years, MACE occurred in 36 (24%) patients: 6 cardiac deaths, 16 second ACS, and 14 coronary revascularizations. Dyslipidaemia (hazard ratio [HR] 3.1 [95% confidence interval 1.5-6.6]) and diabetes mellitus (HR 4.8 [2.3-10.3]) were univariable clinical predictors of MACE. Patients with remaining obstructive non-culprit plaques (HR 3.66 [1.52-8.80]) and higher plaque burden index (HR 1.22 [1.01-1.48]) had a more risk of MACE. In multivariate analysis, with diabetes, dyslipidaemia, and plaque burden index, obstructive non-culprit plaques (HR 3.76 [1.28-11.09]) remained an independent predictor of MACE. CONCLUSION: Almost a quarter of the study population experienced a new event arising from a non-culprit plaque during a follow-up of almost 5 years. ACS patients with remaining obstructive non-culprit plaques or high plaque burden have an increased risk of future MACE.

Effect of body mass index on the image quality of rotational angiography without rapid pacing for planning of transcatheter aortic valve implantation: a comparison with multislice computed tomography.

AIMS: To evaluate the feasibility of procedural planning for transcatheter aortic valve implantation (TAVI) using rotational angiography (R-angio) by comparison with multislice computed tomography (MSCT) and to investigate determinants of the image quality of R-angio. METHODS AND RESULTS: Patients who underwent R-angio of the left ventricle and cardiac MSCT were eligible. R-angio acquisition was performed during contrast injection through a 6F pigtail catheter positioned in the left ventricle. On 3D R-angio and MSCT data sets, diameter measurements were made on short-axis images at the level of the aortic annulus (D(perimeter), D(area)), ascending aorta, sino-tubular junction (ST-junction), and the sinus of Valsalva. At the level of the aortic annulus, diagnostic image quality was obtained in 49 of 56 patients. In all patients with a body mass index (BMI) < 29 kg/m(2), image quality was acceptable whether or not rapid pacing was used. In patients with BMI ≥ 29 kg/m(2), the image quality was poor in 1 of 9 (11%) who were rapidly paced compared with 6 of 12 (50%) who were not. The correlation between R-angio and MSCT measurements was high for aortic annulus D(perimeter), D(area), ST-junction, Valsalva sinus, and ascending aorta (respectively, R = 0.90, 0.90, 0.91, 0.92, and 0.89). The correlations improved further when the analysis was limited to patients with a BMI < 29 kg/m(2) (respectively, 0.92, 0.92, 0.92, 0.92, and 0.93). CONCLUSION: R-angio of the left ventricle allows precise measurement of the aortic root and annulus and was feasible for sizing at the time of TAVI. Diagnostic image quality was obtained without rapid pacing in all patients with a BMI < 29 kg/m(2).

Diagnostic performance of computed tomography coronary angiography to detect and exclude left main and/or three-vessel coronary artery disease.

OBJECTIVES: To determine the diagnostic performance of CT coronary angiography (CTCA) in detecting and excluding left main (LM) and/or three-vessel CAD ("high-risk" CAD) in symptomatic patients and to compare its discriminatory value with the Duke risk score and calcium score. MATERIALS AND METHODS: Between 2004 and 2011, a total of 1,159 symptomatic patients (61 ± 11 years, 31 % women) with stable angina, without prior revascularisation underwent both invasive coronary angiography (ICA) and CTCA. All patients gave written informed consent for the additional CTCA. High-risk CAD was defined as LM and/or three-vessel obstructive CAD (≥50 % diameter stenosis). RESULTS: A total of 197 (17 %) patients had high-risk CAD as determined by ICA. The sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios of CTCA were 95 % (95 % CI 91-97 %), 83 % (80-85 %), 53 % (48-58 %), 99 % (98-99 %), 5.47 and 0.06, respectively. CTCA provided incremental value (AUC 0.90, P < 0.001) in the discrimination of high-risk CAD compared with the Duke risk score and calcium score. CONCLUSIONS: CTCA accurately excludes high-risk CAD in symptomatic patients. The detection of high-risk CAD is suboptimal owing to the high percentage (47 %) of overestimation of high-risk CAD. CTCA provides incremental value in the discrimination of high-risk CAD compared with the Duke risk score and calcium score. KEY POINTS: • Computed tomography coronary angiography (CTCA) accurately excludes high-risk coronary artery disease. • CTCA overestimates high-risk coronary artery disease in 47 %. • CTCA discriminates high-risk CAD better than clinical evaluation and coronary calcification.

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. men at low risk they were 97 % vs. 100 %, 79 % vs. 90 %, 80 % vs. 80 % and 97 % vs. 100 %, respectively. For intermediate risk they were 99 % vs. 99 %, 72 % vs. 83 %, 88 % vs. 93 % and 98 % vs. 99 %, respectively. CONCLUSION: CTCA has similar diagnostic accuracy in women and men at low and intermediate risk. KEY POINTS : • Coronary artery disease (CAD) is increasingly investigated by computed tomography angiography (CTCA). • CAD detection or exclusion by CTCA is not different between sexes. • CTCA diagnostic accuracy was similar between low and intermediate risk sex-specific-groups. • CTCA rarely misses obstructive CAD in low-intermediate risk women and men. • CAD yield by invasive coronary angiography after positive CTCA is similar between sex-risk-specific groups.

Comparison of the value of coronary calcium detection to computed tomographic angiography and exercise testing in patients with chest pain.

The aim of this study was to investigate the value of coronary calcium detection by computed tomography compared to computed tomographic angiography (CTA) and exercise testing to detect obstructive coronary artery disease (CAD) in patients with stable chest pain. A total of 471 consecutive patients with new stable chest complaints were scheduled to undergo dual-source multislice computed tomography (Siemens, Germany; coronary calcium score [CCS] and coronary CTA) and exercise electrocardiography (XECG). Clinically driven invasive quantitative angiography was performed in 98 patients. Only 3 of 175 patients (2%) with a negative CCS had significant CAD on CT angiogram, with only 1 confirmed by quantitative angiography. In patients with a high calcium score (Agatston score >400), CTA could exclude significant CAD in no more than 4 of 65 patients (6%). In patients with a low-intermediate CCS, CTA more often yielded diagnostic results compared to XECG and could rule out obstructive CAD in 56% of patients. For patients with CAD on CT angiogram, those with abnormal exercise electrocardiographic results more often showed severe CAD (p <0.034). In patients with diagnostic results for all tests, the sensitivity and specificity to detect >50% quantitative angiographic diameter stenosis were 100% and 15% for CCS >0, 82% and 64% for CCS >100, 97% and 36% for CTA, and 70% and 76% for XECG, respectively. In conclusion, nonenhanced computed tomography for calcium detection is a reliable means to exclude obstructive CAD in stable, symptomatic patients. Contrast-enhanced CTA can exclude significant CAD in patients with a low-intermediate CCS but is of limited value in patients with a high CCS.

Coronary calcium significantly affects quantitative analysis of coronary ultrasound: importance for atherosclerosis progression/regression studies.

BACKGROUND: Coronary atherosclerosis is a dynamic process, which progresses differently in coronary segments containing noncalcified or calcified plaques. This may have implications for the study of the effects of therapy on progression/regression. OBJECTIVE: To test this hypothesis, we performed a post-hoc analysis on data of a randomized trial in which perindopril treatment was compared with placebo on progression/regression of atherosclerosis with regard to the degree of calcification. METHODS AND RESULTS: The intracoronary ultrasound data of 118 patients, who were enrolled in the multicentre, double-blinded randomized trial (PERSPECTIVE), were analysed. Vessel, lumen and plaque areas were measured in 711 5-mm-long matched coronary segments (perindopril 360, placebo 351). Each individual intracoronary ultrasound cross-section was binary labelled for the presence of calcium (yes/no), and the degree of calcium was assessed as a percentage of length. The segments were classified into three groups: 0-25, 25-50 and 50-100% (percentage of length) calcification. Coronary plaques with no or little calcium (0-25%) regressed on perindopril and did not change on placebo (-0.33+/-1.74 vs. -0.03+/-1.66, respectively; P = 0.04). Plaques containing moderate calcium (group 25-50%) did not change and plaques with severe amounts of calcification (group 50-100%) equally progressed. CONCLUSION: Noncalcified plaques may be amenable to regression with ACE inhibitor treatment. The method, which considers the amount of calcium content in a plaque, may lead to new insights for quantitative analysis of the effects of therapy in progression/regression studies of atherosclerosis.

Three-dimensional and quantitative analysis of atherosclerotic plaque composition by automated differential echogenicity.

OBJECTIVE: To validate automated and quantitative three-dimensional analysis of coronary plaque composition using intracoronary ultrasound (ICUS). BACKGROUND: ICUS displays different tissue components based on their acoustic properties in 256 grey-levels. We hypothesised that computer-assisted image analysis (differential echogenicity) would permit automated quantification of several tissue components in atherosclerotic plaques. METHODS AND RESULTS: Ten 40-mm-long left anterior descending specimens were excised during autopsy of which eight could be successfully imaged by ICUS. Histological sections were taken at 5 mm intervals and analyzed. Since most of the plaques were calcified and having a homogeneous appearance, one specimen with a more heterogeneous composition was further examined: at each interval of 5 mm, 15 additional sections (every 100 microm) were evaluated. Plaques were scored for echogenicity against the adventitia: brighter (hyperechogenic) or less bright (hypoechogenic). Areas of hypoechogenicity correlated with the presence of smooth muscle cells. Areas of hyperechogenicity correlated with presence of collagen, and areas of hyperechogenicity with acoustic shadowing correlated with calcium. None of these comparisons showed statistical significant differences. CONCLUSION: This ex vivo feasibility study shows that automated three-dimensional differential echogenicity analysis of ICUS images allows identification of different tissue types within atherosclerotic plaques. This technology may play a role as an additional tool in longitudinal studies to trace possible changes in plaque composition.

Reproducible coronary plaque quantification by multislice computed tomography.

BACKGROUND: The aim of this study was to investigate reproducibility and accuracy of computer-assisted coronary plaque measurements by multislice computed tomography coronary angiography (QMSCT-CA). METHODS AND RESULTS: Forty-eight patients undergoing MSCT-CA and coronary arteriography for symptomatic coronary artery disease and quantitative intravascular ultrasound (IVUS, QCU) were examined. Two investigators performed the QMSCT-CA twice and a third investigator performed the QCU, all blinded for each other's results. There was no difference found for the matched region of interest (ROI) lengths (QCU 29.4 +/- 13 mm vs. QMSCT-CA 29.6 +/- 13 mm, P = 0.6; total length = 1,400 mm). The comparison of volumetric measurements showed (lumen QCU 267 +/- 139 mm(3) vs. mean QMSCT-CA 177 +/- 91 mm(3), P < 0.001; vessel 454 +/- 194 mm(3) vs. 398 +/- 187 mm(3), P <<0.001; and plaque 189 +/- 93 mm(3) vs. 222 +/- 121 mm(3); investigator 1, P = 0.02; and investigator 2, P = 0.07) significant differences. Automated lumen detection was also applied for QMSCT-CA (218 +/- 112 mm(3), P < 0.001 vs. QCU). The interinvestigator variability measurements for QMSCT-CA showed no significant differences. CONCLUSION: QMSCT-CA systematically underestimates absolute coronary lumen- and vessel dimensions when compared with QCU. However, repeated measurements of coronary plaque by QMSCT-CA showed no statistically significant differences, although, the outcome showed a scattered result. Automated lumen detection for QMSCT-CA showed improved results when compared with those of human investigators.

Drug-eluting stents show delayed healing: paclitaxel more pronounced than sirolimus.

AIMS: To understand wound healing after drug-eluting stents (DES) placement in humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by atherectomy from bare metal stents (BMS) and DES in comparison with de novo atherosclerosis. METHODS AND RESULTS: The tissue was retrieved from ISR in ten sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS, and nine stenotic de novo atherosclerotic lesions and processed for histology and immunocytochemistry. Patients with ISR in PES showed a significantly higher incidence of unstable angina upon presentation for re-intervention (P = 0.046). De novo tissue tended to be more collagen rich, whereas ISR tissue tended to be more proteoglycan rich. In all groups, cell content consisted almost exclusively of smooth muscle cells. Histology showed that fibrinoid in ISR tissue was present only in DES (P = 0.004), as late as 2 years following DES placement, indicating a persistent incomplete healing response. The amount of fibrinoid, given as a percentage of total tissue in each atherectomy specimen, was greater in PES than in SES (17 vs. 5%, P = 0.026). CONCLUSION: ISR in DES shows incomplete neointimal healing as late as 2 years after implantation. Patients with ISR in PES presented with more unstable angina and showed more pronounced signs of delayed healing than SES.

Aortic stiffness is associated with atherosclerosis of the coronary arteries in older adults: the Rotterdam Study.

OBJECTIVE: Aortic stiffness can lead to low diastolic blood pressure, thereby possibly limiting coronary perfusion. Therefore, the simultaneous occurrence of both aortic stiffness and coronary atherosclerosis can lead to an increased risk of subendocardial ischaemia. The aim of the present study was to investigate the association between aortic stiffness and coronary atherosclerosis. METHODS: The study was performed in 1757 subjects of the Rotterdam Study, a population-based study of elderly individuals. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity (PWV). Coronary atherosclerosis was assessed by measuring coronary calcification using electron beam tomography and expressed as a total calcium score. The total calcium score was log-transformed because of its skewed distribution. The association between PWV and coronary calcification was first evaluated after adjustment for age, sex, mean arterial blood pressure and heart rate. RESULTS: Linear regression analyses showed that increased PWV was associated with a higher log total coronary calcium score [beta-regression coefficient 0.11, 95% confidence interval (CI) 0.07-0.15]. Compared with the lowest quartile of PWV, multivariate odds ratios and corresponding 95% CI for advanced coronary calcification in the second, third and fourth highest quartiles were 1.17 (0.79-1.74), 1.58 (1.07-2.34) and 2.12 (1.40-3.20), respectively. CONCLUSIONS: In this large population-based study performed in elderly subjects aortic stiffness was strongly and independently associated with coronary atherosclerosis.

Adjustment method for mechanical Boston scientific corporation 30 MHz intravascular ultrasound catheters connected to a Clearview console. Mechanical 30 MHz IVUS catheter adjustment.

Intracoronary ultrasound (ICUS) is often used in studies evaluating new interventional techniques. It is important that quantitative measurements performed with various ICUS imaging equipment and materials are comparable. During evaluation of quantitative coronary ultrasound (QCU) software, it appeared that Boston Scientific Corporation (BSC) 30 MHz catheters connected to a Clearview ultrasound console showed smaller dimensions of an in vitro phantom model than expected. In cooperation with the manufacturer the cause of this underestimation was determined, which is described in this paper, and the QCU software was extended with an adjustment. Evaluation was performed by performing in vitro measurements on a phantom model consisting of four highly accurate steel rings (perfect reflectors) with diameters of 2, 3, 4 and 5 mm. Relative differences (unadjusted) of the phantom were respectively: 15.92, 13.01, 10.10 and 12.23%. After applying the adjustment: -0.96, -1.84, -1.35 and -1.43%. In vivo measurements were performed on 24 randomly selected ICUS studies. These showed differences for not adjusted vs. adjusted measurements of lumen-, vessel- and plaque volumes of -10.1 +/- 1.5, -6.7 +/- 0.9 and -4.4 +/- 0.6%. An off-line adjustment formula was derived and applied on previous numerical QCU output data showing relative differences for lumen- and vessel volumes of 0.36 +/- 0.51 and 0.13 +/- 0.31%. 30 MHz BSC catheters connected to a Clearview ultrasound console underestimate vessel dimensions. This can retrospectively be adjusted within QCU software as well as retrospectively on numerical QCU data using a mathematical model.

No change in endothelial-dependent vasomotion late after coronary irradiation.

PURPOSE: Mechanical injury from balloon angioplasty and stenting is known to cause prolonged endothelial dysfunction, even distal to the injured segment. Intravascular irradiation therapy is associated with delayed healing response and may therefore also impede endothelial functional recovery. This study was conducted to assess endothelial function late after the irradiation of atherosclerotic coronary arteries. METHODS AND MATERIALS: In 15 patients (8 with additional radiation and 7 with stenting only), directly after the intervention and at 6-month follow-up, endothelial function of the distal segment was studied by assessment of coronary diameter after intracoronary acetylcholine (Ach). Coronary flow reserve (CFR) and intravascular ultrasound (IVUS) investigation were performed for unequivocal interpretation of angiographic data. RESULTS: No significant different response to Ach could be detected at baseline nor at follow-up (-17 +/- 14% vs. -17 +/- 15% for radiation vs. nonradiation at baseline, P=1.0; -8 +/- 11% vs. -9 +/- 13% at follow-up, P=.8). IVUS data revealed more constrictive remodeling in the nonradiation patients, but a minimal increase in mean plaque area in the radiation patients compared with a significant decrease in nonradiation patients (+4% vs. -25%, P=.02). CONCLUSIONS: Irradiation of atherosclerotic coronary arteries does not affect endothelium-dependent vasodilatation acutely or at 6 months. Irradiated segments demonstrated less negative remodeling but higher plaque burden than the controls did.

Effectiveness of sirolimus-eluting stent for treatment of left main coronary artery disease.

The present study reports on the clinical outcome of 31 consecutive patients with left main coronary artery disease treated with a sirolimus-eluting stent. The implantation of this stent was associated with abolition of post-discharge fatal events and percutaneous reintervention.

Clinical introduction of the Tandemheart, a percutaneous left ventricular assist device, for circulatory support during high-risk percutaneous coronary intervention.

BACKGROUND: In patients with poor left ventricular function and high-risk coronary lesions, prolonged ischemia during percutaneous coronary intervention (PCI) may have major hemodynamic consequences. The Tandemheart is a percutaneous left ventricular assist device intended for short-term circulatory support. METHODS AND RESULTS: The Tandem-heart incorporates 9-17 F. arterial cannulae and a unique 21 F. transseptal cannula and centrifugal bloodpump. Operating at 7500 rpm, the pump withdraws oxygenated blood from the left atrium and delivers up to 4 liters/min to the arterial circulation. As of May 2001, the Tandem-heart was electively employed in three male patients (ages 52, 54 and 56) scheduled for high-risk PCI. The mean time to initial circulatory support was less than 30 minutes. Systemic hemodynamics significantly improved prior to PCI in two patients. Pump flow after one hour ranged from 2.43 to 3.8 liters/min (mean 3.17 liters/min) and duration of support from 23 to 49 hours (mean 33 hours). Procedural success was 100%, with no significant hemolysis or bleeding. Successful weaning was completed in all patients, who have remained free of major cardiac events up to seven months post-PCI. CONCLUSIONS: In this first clinical experience of elective use of Tandem-heart for circulatory support during high-risk PCI, the device was easily inserted and preserved hemodynamic stability, regardless of the intrinsic cardiac function, creating optimism for more widespread use for this and other indications.