Lipoprotein apheresis in Germany - Still more commonly indicated than implemented. How can patients in need access therapy?

BACKGROUND: Although lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5-10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of lipoprotein apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD. Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care. METHODS: Based on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure. RESULTS: Working as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy. We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral. CONCLUSIONS: Incidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially above the German average, thus contributing to an extraordinary reduction of cardiovascular events in the population we in particular feel responsible for.

Lipidological competence centres and networks: Future perspectives to improve healthcare of patients with disorders of lipid metabolism.

BACKGROUND: Numerous healthcare studies have shown that more than 90% of all patients with dyslipidaemia are not treated adequately. OBJECTIVES: The "Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen (DGFF)" [German Society of Lipidology], a non-profit professional membership organization, has already made a series of efforts to improve the care of patients suffering from dyslipidaemia. A recent outcome is the nationwide implementation and certification of Lipidological Competence Centres and Networks (LCCNs). METHODS AND RESULTS: By involving numerous external medical cooperation partners and combining the detailed work of different in-house medical specialists, the Medical Care Centre Kempten-Allgäu was able to improve both the diagnosis and treatment of patients exhibiting disorders of lipid metabolism (DLM). This local lipidological network is so successful, that it may serve as a nationwide standard model for outpatient lipidological care. Detailed organizational structures for improved lipidological care which are suitable to provide a template for future guidelines for the certification of LCCNs have been developed by the Medical Care Centre Kempten-Allgäu. Stringent requirements of implementation with respect to medical staff, content and structure, staff training, patient education and public relations as well as to documentation, quality assurance and quality improvement must be fulfilled both by the lipidological competence centre (LCC) and the cooperation partners within the lipidological network (LN). Finally, members of the health care system (e.g. health policy and health insurances) should be involved in this attempt and convinced of financial support. CONCLUSION: The implementation and certification of national LCCNs supported by DGFF could contribute to a comprehensive improvement in the care of patients with dyslipidaemia, resulting in prevention of cardiovascular diseases and reduction of cardiovascular sequelae.

CT Attenuation of Pericoronary Adipose Tissue in Normal Versus Atherosclerotic Coronary Segments as Defined by Intravascular Ultrasound.

BACKGROUND: The factors influencing genesis of atherosclerosis at specific regions within the coronary arterial system are currently uncertain. Local mechanical factors such as shear stress as well as metabolic factors, including inflammatory mediators released from epicardial fat, have been proposed. We analyzed computed tomographic (CT) attenuation of pericoronary adipose tissue in normal versus atherosclerotic coronary segments as defined by intravascular ultrasound (IVUS). PATIENTS AND METHODS: We evaluated the data sets of 29 patients who were referred for invasive coronary angiography and in whom IVUS of 1 coronary vessel was performed for clinical reasons. Coronary CT angiography was performed within 24 hours from invasive coronary angiography. Computed tomographic angiography was performed using dual-source CT (Siemens Healthcare; Forchheim, Germany). A contrast-enhanced volume data set was acquired (120 kV, 400 mA/rot, collimation 2 × 64 × 0.6 mm, 60-80 mL intravenous contrast agent). Intravascular ultrasound was performed using a 40-MHz IVUS catheter (Atlantis; Boston Scientific Corporation, Natick, Mass) and motorized pullback at 0.5 mm/s. Sixty corresponding coronary artery segments within the coronary artery system were identified in both dual source computed tomography and IVUS using bifurcation points as fiducial markers. In dual source computed tomography data sets, 8 serial parallel cross sections (2-mm slice thickness) were rendered orthogonal to the center line of the coronary artery for each segment. For each cross section, pericoronary adipose tissue within a radius of 3 mm from the coronary artery and enclosed within the epicardium (excluding coronary veins and myocardium) was manually traced and mean CT attenuation values were obtained. Intravascular ultrasound was used to define coronary segments as follows: presence of predominantly fibrous atherosclerotic plaque (hyperechoic), presence of predominantly lipid-rich atherosclerotic plaque (hypoechoic), and absence of atherosclerotic plaque. RESULTS: In IVUS, 20 coronary segments with fibrous plaque, 20 segments with lipid-rich plaque, and 20 coronary segments without plaque were identified. The mean CT attenuation of pericoronary adipose tissue for segments with any coronary atherosclerotic plaque was -34 ± 14 Hounsfield units (HU), as compared with -56 ± 16 HU for segments without plaque (P = 0.005). The density of pericoronary fat in segments with fibrous versus lipid-rich plaque as defined by IVUS was not significantly different (-35 ± 19 HU vs -36 ± 16 HU, P = 0.8). CONCLUSIONS: Mean CT attenuation of pericoronary adipose tissue is significantly lower for normal versus atherosclerotic coronary segments. This supports a hypothesis of different types of pericoronary adipose tissue, the more metabolically active of which might exert local effects on the coronary vessels, thus contributing to atherogenesis.

Influence of Cardiovascular Risk Factors on the Prevalence of Coronary Atherosclerosis in Patients with Angiographically Normal Coronary Arteries.

RATIONALE AND OBJECTIVES: Cardiovascular (CV) disease is predominately influenced by CV risk factors and coronary computed tomography angiography (CTA) is capable of detecting early-stage coronary artery disease. We sought to determine the influence of CV risk factors on the prevalence of nonobstructive atherosclerosis in patients with normal-appearing coronary arteries in invasive coronary angiography (ICA). MATERIALS AND METHODS: In this retrospective analysis, we included 60 consecutive symptomatic patients, having undergone ICA and coronary CTA. Coronary dual source CTA was performed using electrocardiogram-triggered retrospective gated image acquisition at 40%-70% of RR interval (tube voltage 100-120 kV, tube current time product 320-440 mAs, 60 mL contrast, and flow rate 6 mL/s). RESULTS: Out of 60 patients (32 men, mean age 61 ± 11 years) with a normal coronary artery appearance in ICA, 45 (75%) patients showed atherosclerotic plaque in CTA. Plaque was present in 14 of 60 (23%) left main, 41 of 60 (68%) left anterior descending, 21 of 60 (35%) circumflex coronary arteries, and 24 of 60 (40%) right coronary arteries. More than 15% of all coronary artery segments showed detectable plaques. Interobserver agreement ranged from good to very good on a per-patient, per-vessel, and per-segment level. Patients with presence of plaque were significantly older (P = 0.005) and showed higher incidence of arterial hypertension (P = 0.019) as compared to individuals without coronary plaque in dual source computed tomography. CONCLUSIONS: The prevalence of coronary atherosclerosis by CTA is substantial in symptomatic patients with normal invasive coronary angiogram. Hypertension and older age significantly influence the prevalence of atherosclerotic plaque and highlight the importance of risk-modifying therapy.

Aortic annulus eccentricity before and after transcatheter aortic valve implantation: Comparison of balloon-expandable and self-expanding prostheses.

INTRODUCTION: The geometry of the aortic annulus and implanted transcatheter aortic valve prosthesis might influence valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of catheter-based aortic valve prostheses. METHODS: Eighty consecutive patients with severe aortic valve stenosis (mean age 82 ± 6 years) underwent computed tomography before and after TAVI. Aortic annulus diameters were determined. Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity were analysed. RESULTS: Aortic annulus eccentricity was reduced in patients after TAVI (0.21 ± 0.06 vs. 0.08 ± 0.06, p<0.0001). Post-TAVI eccentricity was significantly lower in 65 patients following implantation of a balloon-expandable prosthesis as compared to 15 patients who received a self-expanding prosthesis (0.06 ± 0.05 vs. 0.15 ± 0.07, p<0.0001), even though the extent of aortic valve calcification was not different. After TAVI, patients with a higher calcium amount retained a significantly higher eccentricity compared to patients with lower amounts of calcium. CONCLUSIONS: Patients undergoing TAVI with a balloon-expandable prosthesis show a more circular shape of the implanted prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification.

Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: Findings gathered from more than 36,000 treatments at one center in Germany.

LDL cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are main risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 36,745 LA treatments of 118 patients with CVD in a retrospective, monocentric study. Indications were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (n = 35). Average age of patients at start of LA treatment was 58.1 years for males and 62.5 years for females. Medium interval between the first cardiovascular event and LA treatment was 6.4 ± 5.6 years and the average LA treatment period was 6.8 ± 4.9 years. On average treatments were performed once a week, via peripheral venous access in 79.3% of non-hemodialysis patients. In patients with hypercholesterolemia initial pre-LA LDL-C was lowered from 176.4 ± 67.0 mg/dL by 66.7 ± 10.8% per session, achieving a long-term interval mean value of 119.8 ± 34.7 mg/dL, i.e. reduction by 32.1 ± 19.6% (p < 0.0001). In patients with isolated elevated Lp(a) initial pre-LA Lp(a) was lowered from 127.2 ± 67.3 mg/dL by 66.8 ± 5.8% per session, achieving a long-term interval mean value of 60.0 ± 19.5 mg/dL, i.e. reduction by 52.8 ± 23.0% (p < 0.0001). After start of LA the average annual rate of major adverse coronary events (MACE) of all patients declined by 79.7% (p < 0.0001). Subgroup analysis showed decline by 73.7% (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4% (p < 0.0001) in patients with isolated elevated Lp(a). Adverse events (AE) occurred in 1.1% of treatments. LA treatment of patients with high risk for CVD due to LDL and/or Lp(a) hyperlipoproteinemia was effective, safe, and well tolerated. The number of cardiovascular events, at least during a six-year period, declined by 80%.

Clinical benefit of long-term lipoprotein apheresis in patients with severe hypercholesterolemia or Lp(a)-hyperlipoproteinemia with progressive cardiovascular disease.

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Efficacy, safety, and tolerability of lipoprotein apheresis (LA) were investigated in 118 patients with CVD covering a period with 36,745 LA treatments in a retrospective, monocentric study. Indications for LA were severe hypercholesterolemia (n = 83) or isolated Lp(a) hyperlipoproteinemia (Lp(a)-HLP) (n = 35). In patients with hypercholesterolemia, initial pre-LA LDL-C was 176.4 ± 67.0 mg/dL. In patients with isolated Lp(a)-HLP, initial pre-LA Lp(a) was 127.2 ± 67.3 mg/dL. Mean reduction rates of LA were 67 % for both LDL-C and Lp(a). During chronic LA, the average annual rate of major adverse cardiac events of all patients declined by 79.7 % (p < 0.0001). Subgroup analysis showed decline by 73.7 % (p < 0.0001) in patients with severe hypercholesterolemia, and by 90.4 % (p < 0.0001) in patients with isolated Lp(a)-HLP. Adverse events occurred in 1.1 % of treatments. LA treatment of patients with a high risk for CVD due to hypercholesterolemia and/or Lp(a)-HLP demonstrated clinical benefit and was safe and well tolerated.

Comparison of quantitative atherosclerotic plaque burden from coronary CT angiography in patients with first acute coronary syndrome and stable coronary artery disease.

BACKGROUND: Coronary CTA allows characterization of non-calcified and calcified plaque and identification of high-risk plaque features. OBJECTIVE: We aimed to quantitatively characterize and compare coronary plaque burden from CTA in patients with a first acute coronary syndrome (ACS) and controls with stable coronary artery disease. MATERIALS AND METHODS: We retrospectively analyzed consecutive patients with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina with a first ACS, who underwent CTA as part of their initial workup before invasive coronary angiography and age- and gender-matched controls with stable chest pain; controls also underwent CTA with subsequent invasive angiography (total n = 28). Culprit arteries were identified in ACS patients. Coronary arteries were analyzed by automated software to quantify calcified plaque (CP), noncalcified plaque (NCP), and low-density NCP (LD-NCP, attenuation <30 Hounsfield units) volumes, and corresponding burden (plaque volume × 100%/vessel volume), stenosis, remodeling index, contrast density difference (maximum percent difference in attenuation/cross-sectional area from proximal cross-section), and plaque length. RESULTS: ACS patients had fewer lesions (median, 1), with higher total NCP and LD-NCP burdens (NCP: 57.4% vs 41.5%; LD-NCP: 12.5% vs 8%; P ≤ .04), higher maximal stenoses (85.6% vs 53.0%; P = .003) and contrast density differences (46.1 vs 16.3%; P < .006). Per-patient CP burden was not different between ACS and controls. NCP and LD-NCP plaque burden was higher in culprit vs nonculprit arteries (NCP: 57.8% vs 9.5%; LD-NCP: 8.4% vs 0.6%; P ≤ .0003); CP was not significantly different. Culprit arteries had increased plaque lengths, remodeling indices, stenoses, and contrast density differences (46.1% vs 10.9%; P ≤ .001). CONCLUSION: Noninvasive quantitative coronary artery analysis identified several differences for ACS, both on per-patient and per-vessel basis, including increased NCP, LD-NCP burden, and contrast density difference.

Accuracy of prospectively ECG-triggered very low-dose coronary dual-source CT angiography using iterative reconstruction for the detection of coronary artery stenosis: comparison with invasive catheterization.

OBJECTIVE: To evaluate the image quality and diagnostic accuracy of very low-dose computed tomography (CT) angiography (CTA) for the evaluation of coronary artery stenosis. BACKGROUND: Iterative reconstruction (IR) has shown to substantially reduce image noise and hence permit the use of very low-dose data acquisition protocols in coronary CTA. METHODS: Fifty symptomatic patients with an intermediate likelihood for coronary artery disease underwent coronary CTA (heart rate: 59 ± 5 bpm, prospectively ECG-triggered axial acquisition, 100 kV, 160 mAs, 2 × 128 × 0.6 mm collimation, 60 mL contrast, 6 mL/s) prior to invasive coronary angiography. CTA images were reconstructed using both standard filtered back projection (FBP) and a raw data-based IR algorithm [Sinogram Affirmed Iterative Reconstruction (SAFIRE), Siemens Healthcare]. Subjective image quality (four-point Likert scale from 0 = non-diagnostic to 3 = excellent image quality), image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), as well as the presence of coronary stenosis >50% were independently determined by two observers. RESULTS: The mean dose-length product was 46.8 ± 3.5 mGy cm (estimated effective dose 0.66 ± 0.05 mSv). IR led to significantly improved objective image quality compared with FBP (image noise: 41 ± 12 vs. 49 ± 11 HU, P < 0.0001; CNR: 16 ± 8 vs. 12 ± 4, P < 0.0001; SNR: 13 ± 7 vs. 10 ± 3, P < 0.0001). Four coronary segments were not evaluable on FBP data, whereas all segments showed diagnostic image quality with IR. To detect significant coronary stenosis, sensitivity, specificity, positive predictive value, and negative predictive value were 69% (11/16), 97% (175/180), 69% (11/16), and 97% (175/180) per vessel with FBP data sets, respectively. With IR data sets, the corresponding values were 81% (13/16), 97% (178/184), 68% (13/19), and 98% (178/181). These differences were not statistically significant (P = 0.617). CONCLUSIONS: Raw data-based IR significantly improves image quality in very low-dose prospectively ECG-triggered coronary dual-source CTA when compared with standard reconstruction using FBP.

Reproducibility of aortic annulus measurements by computed tomography.

OBJECTIVES: To evaluate a systematic approach for measurement of aortic annulus dimensions by cardiac computed tomography. METHODS: CT data sets of 64 patients were evaluated. An oblique cross-section aligned with the aortic root was created by systematically identifying the caudal insertion points of the three aortic cusps and sequentially aligning them in a double oblique plane. Aortic annulus dimensions, distances of coronary ostia and a suitable fluoroscopic projection angle were independently determined by two observers. RESULTS: Interobserver intraclass correlation coefficients (ICC) for aortic annulus diameters were excellent (ICC 0.89-0.93). Agreement for prosthesis size selection was excellent (ĸ = 0.86 for mean, ĸ = 0.84 for area-derived and ĸ = 0.91 for circumference-derived diameter). Mean distances of the left/right coronary ostium were 13.4 ± 2.4/14.4 ± 2.8 mm for observer 1 and 13.2 ± 2.7/13.5 ± 3.2 mm for observer 2 (p = 0.30 and p = 0.0001, respectively; ICC 0.76/0.77 for left/right coronary artery). A difference of less than 10° for fluoroscopic projection angle was achieved in 84.3% of patients. CONCLUSIONS: A systematic approach to generate a double oblique imaging plane exactly aligned with the aortic annulus demonstrates high interobserver and intraobserver agreements for derived measurements which are not influenced by aortic root calcification. KEY POINTS: • Systematic approach to generate a double oblique imaging plane for TAVI evaluation. • This method is straightforward and software independent. • An approach with high reproducibility, not influenced by aortic root calcification.

Automated attenuation-based selection of tube voltage and tube current for coronary CT angiography: reduction of radiation exposure versus a BMI-based strategy with an expert investigator.

BACKGROUND: Recently developed automated algorithms use the topogram and the corresponding attenuation information before coronary CT angiography (CTA) to allow for an individualized anatomic-based selection of tube current (mAs) and voltage (kV). OBJECTIVES: The value of these algorithms in reducing the associated radiation exposure was evaluated. METHODS: One hundred patients underwent coronary CTA with dual-source CT with prospectively electrocardiogram-triggered axial data acquisition. In all patients, tube parameters (current and voltage) were suggested by both an experienced investigator according to the patient's body mass index (BMI; calculated as weight divided by height squared; kg/m(2)) and by an automated software according to attenuation values of the initial topogram. The first 50 consecutive patients (group 1) underwent coronary CTA with dual-source CT with tube parameters suggested by the experienced investigator (BMI-based tube parameters), whereas in another 50 consecutive patients (group 2) CT data acquisition was performed with tube settings of the automated software. Subsequently, subjective image quality (4-point rating score from 0 = nondiagnostic to 3 = excellent image quality), image noise (SD of CT number within the aortic root), as well as signal- and contrast-to-noise ratios and mean effective radiation doses, were compared between both groups. RESULTS: Both groups showed comparable image quality parameters (group 1 vs 2: noise, 28.1 ± 6.0 HU vs 29.9 ± 5.4 HU, P = .12; signal-to-noise ratio, 16.4 ± 3.9 vs 16.8 ± 4.1, P = .54; contrast-to-noise ratio, 18.6 ± 4.1 vs 19.2 ± 4.3, P = .49; 4-point rating score, 2.8 ± 0.3 vs 2.9 ± 0.3, P = .81). Tube voltage, current, and mean effective radiation dose for groups 1 and 2 were 111 ± 12 kV and 108 ± 12 kV (P = .18), 361 ± 32 mAs and 320 ± 48 mAs (P < .001), and 2.3 mSv (25th; 75th percentile, 1.5; 2.8 mSv) and 1.4 mSv (25th; 75th percentile, 1.1; 1.9 mSv) (P < .001), respectively. CONCLUSIONS: Automated attenuation-based selections of individualized tube parameters are superior to BMI-based selections with expert oversight and show a potential for reduction of radiation exposure in coronary CTA, and image quality is maintained.

Stent evaluation in low-dose coronary CT angiography: effect of different iterative reconstruction settings.

BACKGROUND: Different iterative reconstruction (IR) techniques compensate increased noise from lower tube current-time product settings, yet the differences between IR settings remain unclear. OBJECTIVE: Aim of this study was to test whether different IR settings have a clinically relevant influence on image quality and on the diagnostic accuracy of low-dose CT angiography in patients with a stent. METHODS: Forty-two patients with 73 coronary stents were prospectively enrolled. Data were acquired with dual-source CT, and images were reconstructed with standard filtered back projection (FBP) and raw data-based IR with different settings (I3, I4, I5). Quantitative parameters, including CT-attenuation, noise, signal-to-noise ratio, contrast-to-noise ratio, as well as the presence of in-stent stenosis > 50% were determined. All patients had invasive angiography as reference standard. RESULTS: Mean effective dose was 0.32 ± 0.02 mSv. Image noise decreased significantly compared with FBP (I3 = 29%; I4 = 38% and I5 = 45%), whereas signal-to-noise and contrast-to-noise ratios increased significantly (all IR settings P < .01). Subjective image quality was superior with all IR settings (P < .01). FBP sensitivity, specificity, positive predictive value, and negative predictive value were 83%, 71%, 36%, and 96% per stent compared with 100%, 76%, 44%, and 100%, respectively, in IR reconstructions independent of the IR setting applied. CONCLUSION: In low-dose coronary CT angiography, higher IR settings significantly improved subjective and objective image quality but had no effect on accuracy.

Low-dose dual-source CT angiography with iterative reconstruction for coronary artery stent evaluation.

OBJECTIVES: The purpose of this study was to evaluate the image quality and diagnostic accuracy of very low-dose, dual-source computed tomography (DSCT) angiography for the evaluation of coronary stents. BACKGROUND: Iterative reconstruction (IR) leads to substantial reduction of image noise and hence permits the use of very low-dose data acquisition protocols in coronary computed tomography angiography. METHODS: Fifty symptomatic patients with 87 coronary stents (diameter 3.0 ± 0.4 mm) underwent coronary DSCT angiography (heart rate, 60 ± 6 beats/min; prospectively electrocardiography-triggered axial acquisition; 80 kV, 165 mA, 2 × 128 × 0.6-mm collimation; 60 ml of contrast at 6 ml/s) before invasive coronary angiography. DSCT images were reconstructed using both standard filtered back projection and a raw data-based IR algorithm (SAFIRE, Siemens Healthcare, Forchheim, Germany). Subjective image quality (4-point scale from 0 [nondiagnostic] to 3 [excellent image quality]), image noise, contrast-to-noise ratio as well as the presence of in-stent stenosis >50% were independently determined by 2 observers. RESULTS: The median dose-length product was 23.0 (22.0; 23.0) mGy · cm (median estimated effective dose of 0.32 [0.31; 0.32] mSv). IR led to significantly improved image quality compared with filtered back projection (image quality score, 1.8 ± 0.6 vs. 1.5 ± 0.5, p < 0.05; image noise, 70 Hounsfield units [62; 80 Hounsfield units] vs. 96 Hounsfield units [82; 113 Hounsfield units], p < 0.001; contrast-to-noise ratio, 11.0 [9.6; 12.4] vs. 8.0 [6.2; 9.3], p < 0.001). To detect significant coronary stenosis in filtered back projection reconstructions, the sensitivity, specificity, positive predictive value, and negative predictive value were 97% (32 of 33), 53% (9 of 17), 80% (32 of 40), and 90% (9 of 10) per patient, respectively; 89% (43 of 48), 79% (120 of 152), 57% (42 of 74), and 96% (121 of 126) per vessel, respectively; and 85% (12 of 14), 69% (51 of 73), 32% (11 of 34), and 96% (51 of 53) per stent, respectively. In reconstructions obtained by IR, the corresponding values were 100% (33 of 33), 65% (11 of 17), 85% (33 of 39), and 100% (11 of 11) per patient, respectively; 96% (46 of 48), 84% (129 of 152), 66% (47 of 71), and 98% (127 of 129) per vessel, respectively; and 100% (14 of 14), 75% (55 of 73), 44% (14 of 32), and 100% (55 of 55) per stent, respectively. These differences were not significant. CONCLUSIONS: In selected patients, prospectively electrocardiography-triggered image acquisition with 80-kV tube voltage and low current in combination with IR permits the evaluation of patients with implanted coronary artery stents with reasonable diagnostic accuracy at very low radiation exposure.

CT predictors of post-procedural aortic regurgitation in patients referred for transcatheter aortic valve implantation: an analysis of 105 patients.

Cardiac computed tomography (CT) allows accurate and detailed analysis of the anatomy of the aortic root and valve, including quantification of calcium. We evaluated the correlation between different CT parameters and the degree of post-procedural aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) using the balloon-expandable Edwards Sapien prosthesis. Pre-intervention contrast-enhanced dual source CT data sets of 105 consecutive patients (48 males, mean age 81 ± 6 years, mean logEuroSCORE 34 ± 13%) with symptomatic severe aortic valve stenosis referred for TAVI using the Edwards Sapien prosthesis (Edwards lifesciences, Inc., CA, USA) were analysed. The degrees of aortic valve commissural calcification and annular calcification were visually assessed on a scale from 0 to 3. Furthermore, the degree of aortic valve calcification as quantified by the Agatston score, aortic annulus eccentricity, aortic diameter at the level of the sinus of valsalva and at the sinotubular junction were assessed. Early post-procedural AR was assessed using aortography. Significant AR was defined as angiographic AR of at least moderate degree (AR ≥ 2). Visual assessment of the degree of aortic annular calcification as well as the Agatston score of aortic valve calcium correlated weakly, yet significantly with the degree of post-procedural AR (r = 0.31 and 0.24, p = 0.001 and 0.013, respectively). Compared to patients with AR < 2, patients with AR ≥ 2 showed more severe calcification of the aortic annulus (mean visual scores 1.9 ± 0.6 vs. 1.5 ± 0.6, p = 0.003) as well as higher aortic valve Agatston scores (1,517 ± 861 vs. 1,062 ± 688, p = 0.005). Visual score for commissural calcification did not differ significantly between both groups (mean scores 2.4 ± 0.5 vs. 2.5 ± 0.5, respectively, p = 0.117). No significant correlation was observed between the degree of AR and commissural calcification, aortic annulus eccentricity index or aortic diameters. The extent of aortic valve annular calcification, but not of commissural calcification, predicts significant post-procedural AR in patients referred for TAVI using the balloon-expandable Edwards Sapiens prosthesis.

Patient-specific predictors of image noise in coronary CT angiography.

BACKGROUND: Coronary computed tomography (CT) angiography can be associated with high radiation exposure. Reduction of tube voltage from 120 kV to 100 kV can reduce the dose by up to 40%, but it also increases image noise. OBJECTIVE: We aimed to find a patient-specific predictor of image noise to determine the use of reduced tube voltage. METHODS: Contrast-enhanced coronary dual-source CT angiography data sets [prospectively electrocardiogram (ECG)-triggered axial and retrospectively ECG-gated spiral acquisition, rotation of 280 milliseconds, 2 × 128 × 0.6 mm collimation, 100 kV, 320 mAs] of 165 patients (age, 54 ± 13 years) for the detection of coronary artery stenoses were analyzed. Image noise was measured in the aortic root. Influence of body weight, height, body mass index, thoracic cross sectional area, as well as the area of the thoracic solid tissue were analyzed. RESULTS: Mean image noise in the aorta was 35.1 ± 8.9 HU. Mean dose length product was 207 ± 184 cm · cGy with an average effective dose of 2.9 ± 2.6 mSv. The patient cohort was divided into tertiles according to image noise. Numerous parameters, including BMI and body weight, were significantly different between the highest and lowest tertiles. In multivariable regression analysis, the area of the thoracic solid tissue was the only independent predictor of image noise (P < 0.0001). CONCLUSIONS: The area of the thoracic solid tissue at the level of the aortic root predicts image noise and may hence be used for the decision to reduce tube voltage from 120 kV to 100 kV.

Very low-dose coronary artery calcium scanning with high-pitch spiral acquisition mode: comparison between 120-kV and 100-kV tube voltage protocols.

BACKGROUND: Effective radiation dose from a single coronary artery calcification CT scan can range from 0.8 to 10.5 mSv, depending on the protocol. Reducing the effective radiation dose to reasonable levels without affecting diagnostic image quality can result in substantial dose reduction in CT. OBJECTIVES: We prospectively compared tube voltages of 120 and 100 kV in a low-dose CT acquisition protocol for measuring coronary artery calcified plaque with prospectively electrocardiogram (ECG)-triggered high-pitch spiral acquisition. METHODS: In 150 consecutive patients, measurement of coronary artery calcified plaque was performed with prospectively ECG-triggered high-pitch spiral acquisition. Imaging was first done with tube voltage of 120 kV voltage and subsequently repeated with 100 kV and otherwise unchanged parameters. CT was performed with a dual-source CT system with 280 milliseconds of rotation time, 2 × 128 slices, pitch of 3.4, triggered at 60% of the R-R interval. Tube current for both protocols was set at 80 mAs. With the use of a medium sharp reconstruction kernel (Siemens B35f), cross-sectional images were reconstructed with 3.0-mm slice thickness and 1.5-mm increment. Agatston scores were determined per patient for both scan settings by 2 independent readers with the use of a standard threshold of 130 HU for calcium detection. In addition, the Agatston score was calculated with a previously proposed threshold of 147 HU for 100-kV acquisitions. RESULTS: Mean image noise was 20 ± 5 and 27 ± 7 for 120 and 100 kV, respectively (P < 0.0001). Mean dose length product was 24 ± 6 cm · cGy for the 120-kV protocol and 14 ± 4 cm · cGy for the 100-kV protocol, corresponding to average estimated effective doses of 0.3 and 0.2 mSv (P < 0.0001). Five patients were excluded from the analysis. In the remaining 145 patients, using the standard tube voltage of 120 kV, any coronary calcium was detected in 76 identical patients by both observers. In 75 of these patients, calcium was also identified by both observers in 100-kV data sets, whereas 1 patient was scored negative by 1 reader and was assigned an Agatston score of 0.7 (threshold, 130 HU) and 0.2 (threshold, 147 HU) by the other. Interobserver disagreement for assigning a patient a zero Agatston score was the same for both scan settings (each 4 patients). The mean Agatston scores for 120-kV and 100-kV (threshold, 147 HU) scans were 105 ± 245 (range, 0-1865) and 116 ± 261 (range, 0-1917), respectively (P < 0.0001). Bland-Altman analysis indicated a systematic overestimation of the Agatston score with tube voltage of 100 kV and threshold of 147 HU (mean difference, 11; 95% limits of agreement, 62 to -40). Similar results were observed for coronary calcium volume scores. CONCLUSION: High-pitch spiral acquisition allows coronary calcium scoring with effective doses below 0.5 mSv. The use of 100-kV tube voltage further reduces effective radiation dose compared with the standard of 120 kV; however, it leads to significant overestimation of the Agatston score when the standard threshold of 130 HU is used. Adjusting the threshold to 147 HU leads to a better agreement compared with standard 120 kV protocols yet with a remaining systematic bias toward overestimation of the Agatston score. For high-pitch spiral acquisition mode, effective radiation dose reduction when using a 100-kV setting is minimal compared with the standard 120-kV setting and may be considered nonsignificant in a clinical setting.

Image quality of ultra-low radiation exposure coronary CT angiography with an effective dose <0.1 mSv using high-pitch spiral acquisition and raw data-based iterative reconstruction.

OBJECTIVES: We evaluated the potential of prospectively ECG-triggered high-pitch spiral acquisition with low tube voltage and current in combination with iterative reconstruction to achieve coronary CT angiography with sufficient image quality at an effective dose below 0.1 mSv. METHODS: Contrast-enhanced coronary dual source CT angiography (2 × 128 × 0.6 mm, 80 kV, 50 mAs) in prospectively ECG-triggered high-pitch spiral acquisition mode was performed in 21 consecutive individuals (body weight <100 kg, heart rate ≤60/min). Images were reconstructed with raw data-based filtered back projection (FBP) and iterative reconstruction (IR). Image quality was assessed on a 4-point scale (1 = no artefacts, 4 = unevaluable). RESULTS: Mean effective dose was 0.06 ± 0.01 mSv. Image noise was significantly reduced in IR (128.9 ± 46.6 vs. 158.2 ± 44.7 HU). The mean image quality score was lower for IR (1.9 ± 1.1 vs. 2.2 ± 1.0, P < 0.0001). Of 292 coronary segments, 55 in FBP and 40 in IR (P = 0.12) were graded "unevaluable". In patients with a body weight ≤75 kg, both in FBP and in IR, the rates of fully evaluable segments were significantly higher in comparison to patients >75 kg. CONCLUSIONS: Coronary CT angiography with an estimated effective dose <0.1 mSv may provide sufficient image quality in selected patients through the combination of high-pitch spiral acquisition and raw data-based iterative reconstruction.

Accuracy of automated software-guided detection of significant coronary artery stenosis by CT angiography: comparison with invasive catheterisation.

PURPOSE: True automated detection of coronary artery stenoses might be useful whenever expert evaluation is not available, or as a "second reader" to enhance diagnostic confidence. We evaluated the accuracy of a PC-based stenosis detection tool alone and combined with expert interpretation. METHODS: One hundred coronary CT angiography datasets were evaluated with the automated software alone, by manual interpretation (axial images, multiplanar reformations and maximum intensity projections in free double-oblique planes), and by expert interpretation aware of the automated findings. Stenoses ≥ 50 % were noted per-vessel and per-patient, and compared with invasive angiography. RESULTS: Automated post-processing was successful in 90 % of patients (88 % of vessels). When excluding uninterpretable datasets, per-patient sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89 %, 79 %, 74 % and 92 % (per-vessel: 82 %, 85 %, 48 % and 96 %). All 100 datasets were evaluable by expert interpretation. Per-patient sensitivity, specificity, PPV and NPV were 95 %, 95 %, 93 % and 97 % (per-vessel: 89 %,98 %, 88 % and 98 %). Knowing the results of automated interpretation did not improve the performance of expert readers. CONCLUSION: Automated off-line post-processing of coronary CT angiography shows adequate sensitivity, but relatively low specificity in coronary stenosis detection. It does not increase accuracy of expert interpretation. Failure of post-processing in 10 % of all patients necessitates additional manual image work-up. KEY POINTS: • Coronary CT angiography is increasingly used for detection of coronary artery stenosis • Computer assisted diagnosis might facilitate and speed up interpretation • Performance in properly segmented cases compared favourably with manual image interpretation • However, automated segmentation failed in about 10 % of cases • Manual reading is still mandatory; computer assisted diagnosis can provide a useful second read.

A method to determine suitable fluoroscopic projections for transcatheter aortic valve implantation by computed tomography.

BACKGROUND: In transcatheter aortic valve implantation (TAVI), optimal selection of fluoroscopic projections that permit orthogonal visualization of the aortic valve plane is important but may be difficult to achieve. OBJECTIVE: We developed and validated a simple method to predict suitable fluoroscopic projections on the basis of cardiac CT datasets. METHODS: In 75 consecutive patients that underwent TAVI, angulations in which a 35-mm thick maximum intensity projection would render all aortic valve calcium into 1 plane were determined by manual interaction with contrast-enhanced dual-source CT datasets. TAVI operators used the predicted angulation for the first aortic angiogram and performed additional aortic angiograms if no satisfactory view of the aortic valve plane was obtained. Predicted angulations were compared with the angulation used for valve implantation. Radiation exposure and contrast use was compared between patients with accurate prediction of fluoroscopic angulations by CT and patients in whom CT failed to predict a suitable view. RESULTS: The mean difference between the predicted angulation according to CT and the angulation used for implantation was 3 ± 6 degrees. CT predicted a suitable angulation (<5-degree deviation) in 63 of 75 cases (84%). The mean number of aortic angiograms acquired in patients with correct prediction (1.02 ± 0.1) was significantly lower than in patients with incorrect prediction of the implantation angle by CT (3.0 ± 1.7; P < 0.001). Contrast agent required for the entire TAVI procedure was lower in patients with correct prediction (72 ± 36 mL vs 106 ± 39 mL; P = 0.001). CONCLUSION: CT permits prediction of suitable angulations for TAVI in most cases.

Left ventricular thrombus attenuation characterization in cardiac computed tomography angiography.

BACKGROUND: Because of their similar visual appearance, differentiation of left ventricular thrombotic material and myocardial wall can be difficult in contrast-enhanced coronary computed tomography (CT) angiography. OBJECTIVE: We identified typical thrombi attenuation of left ventricular thrombi with the use of CT measurement. METHODS: Over a time period of 6 years, we retrospectively identified 31 patients who showed a left ventricular thrombus in CT angiography datasets. Patients underwent routine contrast cardiac CT to investigate coronary artery disease. CT attenuation of each thrombus was assessed in the 4-chamber view. CT densities were also determined in the ascending aorta, left ventricle, and myocardial wall both in the mid-septal and mid-lateral segments. The mean CT attenuation of thrombi and the difference between attenuation in thrombi, left ventricular cavity, and myocardial wall were determined. The ratio of attenuation values in thrombus versus aorta and myocardium versus aorta were also determined. RESULTS: Mean (±SD) CT attenuation of all left ventricular thrombi in 31 patients was 43.2 ± 15.3 HU (range, 25-80 HU). Mean CT densities of septal and lateral myocardial wall were 102.9 ± 23.1 HU (range, 63-155 HU) and 99.3 ± 28.7 HU (range, 72-191 HU), respectively, and were thus significantly higher than the CT attenuation of thrombi (P < 0.001). A threshold of 65 HU yielded a sensitivity, specificity, and positive and negative predictive values of 94%, 97%, 94%, and 97%, respectively, to differentiate thrombus from the myocardial wall. The mean ratio between CT attenuation of thrombus and CT attenuation within the ascending aorta was 0.11 ± 0.05 (range, 0.04-0.23), which was significantly lower compared with the mean ratio between CT attenuation of the myocardial wall and the CT attenuation within the ascending aorta. CONCLUSION: CT attenuation within left ventricular thrombi was significantly lower than myocardial attenuation in CT angiography datasets. Assessment of CT attenuation may contribute to the differentiation of thrombi.