Coronary computed tomography angiography based assessment of endothelial shear stress and its association with atherosclerotic plaque distribution in-vivo.

PURPOSE: The relationship between low endothelial shear stress (ESS) and coronary atherosclerosis is well established. ESS assessment so far depended on invasive procedures. The aim of this study was to demonstrate the relationship between ESS and coronary atherosclerosis by using non-invasive coronary computed tomography angiography (CTA) for computational fluid dynamics (CFD) simulations. METHODS: A total number of 7 consecutive patients with suspected coronary artery disease who received CTA and invasive angiography with IVUS analysis were included in this study. CTA examinations were performed using a dual-source scanner. These datasets were used to build a 3D mesh model. CFD calculations were performed using a validated CFD solver. The presence of plaque was assumed if the thickness of the intima-media complex exceeded 0.3 mm in IVUS. Plaque composition was derived by IVUS radiofrequency data analysis. RESULTS: Plaque was present in 32.1% of all analyzed cross-sections. Plaque prevalence was highest in areas of low ESS (49.6%) and high ESS (34.8%). In parts exposed to intermediate-low and intermediate-high ESS few plaques were found (20.0% and 24.0%) (p<0.001). Wall thickness was closely associated with local ESS. Intima-media thickness was 0.43±0.34 mm in low and 0.38±0.32 mm in high ESS segments. It was significantly lower when the arterial wall was exposed to intermediate ESS (0.25±0.18 mm and 0.28 ± 0.20 mm) (p<0.001). Fibrofatty tissue was predominately found in areas exposed to low ESS (p≤0.023). CONCLUSIONS: In this study a close association of atherosclerotic plaque distribution and ESS pattern could be demonstrated in-vivo. Adding CFD analysis to coronary CTA offers the possibility to gather morphologic and physiologic data within one non-invasive examination.

Assessment of the presence and extent of coronary collateralization by coronary computed tomographic angiography in patients with total occlusions.

Coronary computed tomography angiography (CTA) may be helpful to manage patients with chronic coronary occlusions. The aim of this study was to determine the sensitivity and specificity of CTA to detect the presence and extent of coronary collaterals as compared to invasive coronary angiography (ICA). We retrospectively evaluated 26 patients who underwent both coronary CTA and ICA within 3 weeks and demonstrated a total coronary occlusion (TIMI grade 0) in one of the major coronary arteries. CTA was performed using a 64-slice multidetector CT. The presence, and extent of collateralization was assessed by two blinded observers using the Rentrop classification for ICA. CTA accurately identified the presence and location of all 26 total occlusions. The presence of any collaterals was accurately detected in 21/23 patients [sensitivity 91% (CI: 71-98%)] and the absence in three patients [specificity 100% (CI: 29%-100%)]. The sensitivity of coronary CTA to identify patients with collateralization increased from 91 to 94% (CI: 71-99%) and 100% (CI: 59-100%) for collaterals Rentrop grade 2 and 3 in ICA, respectively. Coronary CTA accurately detects the presence of any coronary collateralization in patients with total occlusions. Although CT technology is currently limited in the assessment of individual collaterals and smaller vessels, it may be helpful in the management of patients with total occlusions.

Assessment and characterization of time-related differences in plaque composition by intravascular ultrasound-derived radiofrequency analysis in heart transplant recipients.

BACKGROUND: The survival of heart transplant patients is limited by cardiac allograft vasculopathy (CAV). Intravascular ultrasound (IVUS) and IVUS-derived radiofrequency plaque composition analysis (IVUS-RF) provide further information about the process of coronary atherosclerosis. METHODS: In this study we aimed to assess the time-dependent differences in disease progression in patients with CAV. Fifty-six patients were divided into three groups according to time interval after transplantation (Group I: 1 to 3 months, 18 patients; Group II, 1 to 5 years, 20 patients; Group III: 5 to 15 years, 18 patients). RESULTS: IVUS-RF revealed time-dependent increases in all plaque components. The largest increase was shown for fibrotic, fibrofatty and necrotic tissue between Groups I and II. Dense calcium area increased uniformly in all groups. IVUS-RF-derived plaque type analysis revealed predominantly fibrotic plaques in all groups with a decrease of frequency over time. Fibrolipidic and fibrotic-calcific plaques increased uniformly. High-risk lesions, such as thick-cap fibroatheromas (FAs), increased in Groups I and II and decreased in Group III. Thin-cap FAs were detected only in Group III. CONCLUSIONS: IVUS-RF, as compared with gray-scale IVUS, provides better detailed information about the development of CAV by plaque morphology and composition analysis in different stages after heart transplantation. Serial IVUS-RF analysis in these patients may improve the stratification of heart transplant recipients.

Assessment of early atherosclerosis in de novo heart transplant recipients: analysis with intravascular ultrasound-derived radiofrequency analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the major limitation in survival of patients after heart transplantation. Cardiac allograft vasculopathy is angiographically silent in the early phase after operation. Intravascular ultrasound (IVUS) is a more sensitive method to detect the early stages of CAV and provides information about its development. Recent IVUS studies demonstrated a rapid progression of CAV within the first year after transplantation as a predictor of morbidity and mortality. OBJECTIVES: This study assessed the plaque composition of early atherosclerosis in transplant patients by radiofrequency analysis. METHODS: Coronary angiography and IVUS with Virtual Histology (VH) software (Real-Time VH, Volcano Corp, Rancho Cordova, CA) were used to assess 18 patients early after heart transplantation (1.71 +/- 0.47 months). The plaque composition was determined by IVUS radiofrequency data analysis. Tissue maps were reconstructed from radiofrequency data using VH-IVUS software. The VH-IVUS acquisition was performed with standardized IVUS (EagleEye catheter; 2.9 F/20 MHz; Volcano Corp) and the VH-IVUS console (Volcano Corp). RESULTS: Coronary angiography did not show any wall irregularities. Intravascular ultrasound demonstrated donor-transmitted atherosclerosis in 6 of 18 patients (33.33%). The incidence, amount of plaque burden, and plaque composition was significantly related to donor age. By VH-IVUS analysis, the plaque composition consisted mainly of fibrotic tissue. CONCLUSIONS: Donor-transmitted coronary atherosclerosis is present early after heart transplantation and cannot be detected by coronary angiography. VH-IVUS gives detailed information about the plaque distribution and the plaque composition.

Measurement of fractional flow reserve to guide decisions for percutaneous coronary intervention.

BACKGROUND: Coronary artery disease (CAD) is one of the leading causes of premature death in Germany. Percutaneous coronary interventions (PCI) are frequently performed in patients with angiographically intermediate stenoses. However, the necessity of PCI has not been proven for all patients. Pressure-based fractional flow reserve (FFR) is an invasive test that can be used to assess the functional significance of intermediate coronary stenoses in order to guide decisions on PCI. OBJECTIVES: This health technology assessment (HTA) aims to evaluate (1) the diagnostic accuracy, (2) the risk-benefit trade-off and (3) the long-term cost-effectiveness of FFR measurement to guide the decision on PCI in patients with stable angina pectoris and intermediate coronary stenoses. METHODS: We performed a literature search in medical and HTA databases. We used the DIMDI instruments (DIMDI = Deutsches Institut für Medizinische Dokumentation und Information/German Institute for Medical Information and Documentation) to assess study quality and to extract and summarize the information in evidence tables. We performed a meta-analysis to calculate the pooled overall estimate for sensitivity and specificity of FFR with 95% confidence intervals (95% CI). Individual studies' case numbers were used as weights. The influence of single studies and important covariates on the results was tested in sensitivity analyses. We developed the German Coronary Artery Disease Outcome Model (German CADOM), a decision-analytic Markov model, to estimate the long-term effectiveness and cost-effectiveness of FFR measurement in the context of the German healthcare system. RESULTS: Our literature search identified twelve studies relevant to this HTA-report including ten diagnostic accuracy studies of FFR measurement, one randomized clinical trial (RCT) investigating the clinical benefits of this technique as well as one economic evaluation. Pooled estimates for sensitivity and specificity were 81.7% (95% CI: 77.0-85.7%) and 78.7% (95% CI: 74.3-82.7%). Sensitivity analyses indicated robust results. The RCT investigating the efficacy of an FFR-based treatment strategy provided evidence of the advantages of this strategy for patients with respect to freedom from angina and major adverse cardiac events. The published cost-effectiveness study demonstrates that the FFR-based strategy is cost-saving in the US context. Based on our own decision analysis for the German context, the FFR-based strategy improves (quality-adjusted) life-expectancy when compared to universal PCI and is cost-effective in the German healthcare context. This HTA is limited by the use of poor gold standards in several of the included diagnostic studies as well as the ongoing advance of technology and treatment options in interventional cardiology. Results of the decision analysis are limited by the necessary underlying assumptions and the uncertainty regarding long-term mortality reduction associated with PCI. Further research should focus on the acquisition of long-term data for disease progression in patients with and without functional coronary stenoses as well as the benefits and risks of PCI. CONCLUSIONS: Based on actual evidence and our decision analysis, the use of FFR measurement to guide the decision on PCI should lead to better short- and long-term clinical outcomes in patients with stable angina and single-vessel disease without documented myocardial ischemia and it should provide a cost-effective use of resources in the German healthcare system. FFR measurement should be introduced in routine clinical practice. However, appropriate reimbursement strategies are necessary to avoid wrong incentives.

Cardiac magnetic resonance perfusion imaging for the functional assessment of coronary artery disease: a comparison with coronary angiography and fractional flow reserve.

AIMS: Cardiac magnetic resonance perfusion imaging (CMRI) is a promising technique for non-invasive measurement of myocardial perfusion reserve. Fractional flow reserve (FFR) is an established invasive method for functional assessment of coronary artery disease (CAD). To prospectively assess the diagnostic value of CMRI for the detection of haemodynamically significant coronary lesions, compared with coronary angiography (CA) and FFR. METHODS AND RESULTS: Forty-three patients with suspected or known CAD underwent CA, CMRI, and FFR measurement. First pass magnetic resonance perfusion examination was performed during hyperaemia (140 microg/kg/min adenosine over 6 min) and at rest. One hundred and twenty-nine perfusion territories were assessed by semi-quantitative evaluation of signal intensity-time curves using the myocardial perfusion reserve index (MPRI) [upslope(stress(corrected))/upslope(rest(corrected))]. Perfusion territories were categorized as normal (coronary stenosis < or = 50%), intermediate (stenosis > 50% and FFR > 0.75), or severe (stenosis > 50% and FFR < or = 0.75 or total occlusion). MPRI values (+/-SD) were significantly different between the three categories [normal, 2.2 +/- 0.5 vs. intermediate, 1.8 +/- 0.5 (P = 0.005) and intermediate vs. severe, 1.2 +/- 0.3 (P < 0.001)]. An MPRI cut-off value of 1.5 (derived from receiver operating characteristics analysis) distinguished haemodynamically relevant (severe) from non-relevant (normal and intermediate) stenoses with a sensitivity of 88% (CI 74-100%) and a specificity of 90% (CI 84-96%). CONCLUSION: In contrast to earlier studies that compared CMRI with morphological examination (CA) alone, the present study compared CMRI with CA plus a standard invasive functional assessment (FFR) and demonstrated that CMRI is able to distinguish haemodynamically relevant from non-relevant coronary lesions with a high sensitivity and specificity and may therefore contribute to clinical decision-making.

Single-shot inversion recovery TrueFISP for assessment of myocardial infarction.

OBJECTIVE: The aim of the study was to assess the diagnostic accuracy of imaging the myocardium with a fast multislice inversion recovery 2D single-shot true fast imaging with steady-state precession (trueFISP) sequence during a single breath-hold in comparison with an established segmented inversion recovery turbo fast low-angle shot (turboFLASH) sequence. SUBJECTS AND METHODS: Forty-three patients with myocardial infarction were examined on a 1.5-T MR system 10 min after administration of contrast material (gadodiamide, 0.2 mmol/kg) with a single-shot 2D multislice technique (single-shot inversion recovery trueFISP) that allows one to image the entire short axis during one breath-hold (18 heartbeats) and with a segmented 2D single-slice technique (inversion recovery turboFLASH) that requires one breath-hold per slice (12 heartbeats). Signal intensity was determined in normal myocardium, in infarcted myocardium, and in the left ventricle. The contrast-to-noise ratio (CNR) of normal and infarcted myocardium was determined. The areas of hyperintense infarctions on selected slices and the entire volumes were compared for both sequence techniques. RESULTS: The inversion recovery trueFISP sequence has a lower CNR than the inversion recovery turboFLASH sequence (mean values, 10.0 vs 12.9, respectively; p = 0.005) for differentiation of viable from nonviable myocardium. The CNR of injured myocardium and blood in the left ventricular cavity also has a lower value for the multislice technique compared with the single-slice technique (0.6 vs 1.2, respectively; p = 0.045). Assessment of the area of infarction within one slice (r = 0.97, p < 0.002) and of the volume of the entire infarction (r = 0.96, p < 0.003) is possible with excellent correlation of both techniques. CONCLUSION: Despite having a lower CNR, the inversion recovery 2D single-shot trueFISP sequence allows fast and accurate identification of the area and volume of infarction with high spatial resolution within a single breath-hold.

Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

BACKGROUND: Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared with intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route. METHODS: FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 microg as boli) and a standard intravenous infusion of 140 microg/kg/min were administered in a randomized fashion. RESULTS: Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-microg intracoronary bolus and 140-microg/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-microg bolus, resulted in mean FFR values that were significantly (P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-microg intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration. CONCLUSIONS: This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 microg. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 microg/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR.