Patient-Specific Simulations of Transcatheter Aortic Valve Stent Implantation

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) enables treatment of aortic stenosis with no need for open heart surgery. According to current guidelines, only patients considered at high surgical risk can be treated with TAVI. In this study, patient-specific analyses were performed to explore the feasibility of TAVI in morphologies, which are currently borderline cases for a percutaneous approach.

METHODS: Five patients were recruited: four patients with failed bioprosthetic aortic valves (stenosis) and one patient with an incompetent, native aortic valve. Three-dimensional models of the implantation sites were reconstructed from computed tomography images. Within these realistic geometries, TAVI with an Edwards Sapien stent was simulated using finite element (FE) modelling. Engineering and clinical outcomes were assessed.

RESULTS: In all patients, FE analysis proved that TAVI was morphologically feasible. After the implantation, stress distribution showed no risks of immediate device failure and geometric orifice areas increased with low risk of obstruction of the coronary arteries. Maximum principal stresses in the arterial walls were higher in the model with native outflow tract.

CONCLUSIONS: FE analyses can both refine patient selection and characterise device mechanical performance in TAVI, overall impacting on procedural safety in the early introduction of percutaneous heart valve devices in new patient populations.

PMID: 22286953

Deformation Dynamics and Mechanical Properties of the Aortic Annulus by 4-Dimensional Computed Tomography Insights into the Functional Anatomy of the Aortic Valve Complex and Implications for Transcatheter Aortic Valve Therapy

OBJECTIVES: The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation.

METHODS: Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Young’s elastic module was calculated from the stress-strain relationship of the annulus.

RESULTS: In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Young’s modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects.

CONCLUSIONS: The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.

PMID: 22222074

Resting Coronary Flow Velocity in the Functional Evaluation of Coronary Artery Stenosis: Study on Sequential Use of Computed Tomography Angiography and Transthoracic Doppler Echocardiography

OBJECTIVES: Accelerated flow at the site of flow-limiting stenosis can be detected by transthoracic Doppler echocardiography (TTDE). We studied feasibility and accuracy of sequential coronary computed tomography angiography (CTA) and TTDE in detection of haemodynamically significant coronary artery disease (CAD).

METHODS: We prospectively enrolled 107 patients with intermediate (30-70%) pre-test likelihood of CAD. All patients underwent CTA using a 64-slice scanner. Using TTDE, the ratio of maximal diastolic flow velocity to pre-stenotic flow velocity (M/P ratio) was measured in the coronary segments with stenosis in CTA. In all patients, the results were compared with invasive coronary angiography, including measurement of fractional flow reserve when appropriate. All analyses were done blinded.

RESULTS: TTDE was feasible in 276 of 285 evaluated coronary segments. Significant coronary stenoses were associated with a higher M/P ratio than non-significant stenoses (3.59 ± 1.82 vs. 1.28 ± 0.60, P < 0.001). The optimal M/P ratio for detection of significant stenosis was 2.2 (area under receiver operating characteristic curve 0.92, P < 0.001). Compared with the strategy of CTA alone, sequential CTA and focused TTDE had a better positive predictive value (PPV; 61 vs. 78%) and diagnostic accuracy (93 vs. 96%, P = 0.006) without impairment of the negative predictive value (97 vs. 97%).

CONCLUSIONS: Sequential use of CTA and TTDE is feasible for combined anatomic and functional evaluation of coronary stenoses. Compared with coronary CTA alone, addition of TTDE improved PPV for detection of significant CAD.

PMID: 21880607

Patient Management After Noninvasive Cardiac Imaging – Results From SPARC (Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease)

OBJECTIVES: This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear.

METHODS: We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography.

RESULTS: Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results.

CONCLUSIONS: Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings.

PMID:

Reference Values for Normal Pulmonary Artery Dimensions by Noncontrast Cardiac Computed Tomography: The Framingham Heart Study

OBJECTIVES: Main pulmonary artery diameter (mPA) and ratio of mPA to ascending aorta diameter (ratio PA) derived from chest CT are commonly reported in clinical practice. We determined the age- and sex-specific distribution and normal reference values for mPA and ratio PA by CT in an asymptomatic community-based population.

METHODS: In 3171 men and women (mean age, 51±10 years; 51% men) from the Framingham Heart Study, a noncontrast, ECG-gated, 8-slice cardiac multidetector CT was performed. We measured the mPA and transverse axial diameter of the ascending aorta at the level of the bifurcation of the right pulmonary artery and calculated the ratio PA. We defined the healthy referent cohort (n=706) as those without obesity, hypertension, current and past smokers, chronic obstructive pulmonary disease, history of pulmonary embolism, diabetics, cardiovascular disease, and heart valve surgery.

RESULTS: The mean mPA diameter in the overall cohort was 25.1±2.8 mm and mean ratio PA was 0.77±0.09. The sex-specific 90th percentile cutoff value for mPA diameter was 28.9 mm in men and 26.9 mm in women and was associated with increase risk for self-reported dyspnea (adjusted odds ratio, 1.31; P=0.02). The 90th percentile cutoff value for ratio PA of the healthy referent group was 0.91, similar between sexes but decreased with increasing age (range, 0.82-0.94), though not associated with dyspnea.

CONCLUSIONS: For simplicity, we established 29 mm in men and 27 mm in women as sex-specific normative reference values for mPA and 0.9 for ratio PA.

PMID: 22178898

Relation Between Estimated Glomerular Filtration Rate and Composition of Coronary Arterial Atherosclerotic Plaques

OBJECTIVES: It is well known that chronic kidney disease is a risk factor for atherosclerosis. The present study was conducted to identify any relation between the estimated glomerular filtration rate (eGFR) and coronary plaque characteristics using integrated backscatter intravascular ultrasound (IB-IVUS), which can detect coronary plaque composition.

METHODS: We performed IB-IVUS for 201 consecutive patients undergoing percutaneous coronary intervention, and they were divided into 3 groups according to the eGFR values (group 1 [n = 20], ≥90 ml/min/1.73 m(2); group 2 [n = 123], 60 to 90 ml/min/1.73 m(2); and group 3 [n = 58], <60 ml/min/1.73 m(2)). Coronary plaques in nonculprit lesions on 3-dimensional analysis were evaluated using IB-IVUS.

RESULTS: The baseline characteristics were similar, except for older age and a greater prevalence of men in group 3. IB-IVUS showed a percentage of lipid volume of 44.7 ± 5.0% in group 1, 53.6 ± 6.2% in group 2, and 63.5 ± 6.2% in group 3 (p <0.01), with a corresponding percentage of fibrous volume of 53.9 ± 4.9%, 45.1 ± 6.0%, and 35.3 ± 6.1%, respectively (p <0.01). The eGFR correlated significantly with both parameters (r = -0.68, p <0.001 and r = 0.68, p <0.001, respectively).

CONCLUSIONS: In conclusion, lower eGFR levels were associated with greater lipid and lower fibrous contents, contributing to coronary plaque vulnerability.

PMID: 22245411

Ex Vivo Assessment of Vascular Response to Coronary Stents By Optical Frequency Domain Imaging

OBJECTIVES: This study sought to examine the capability of optical frequency domain imaging (OFDI) to characterize various morphological and histological responses to stents implanted in human coronary arteries. A precise assessment of vascular responses to stents may help stratify the risk of future adverse events in patients who have been treated with coronary stents.

METHODS: Fourteen human stented coronary segments with implant duration ≥1 month from 10 hearts acquired at autopsy were interrogated ex vivo by OFDI and intravascular ultrasound (IVUS). Comparison with histology was assessed in 134 pairs of images where the endpoints were to investigate: 1) accuracy of morphological measurements; 2) detection of uncovered struts; and 3) characterization of neointima.

RESULTS: Although both OFDI and IVUS provided a good correlation of neointimal area with histology, the correlation of minimum neointimal thickness was inferior in IVUS (R(2) = 0.39) as compared with OFDI (R(2) = 0.67). Similarly, IVUS showed a weak correlation of the ratio of uncovered to total stent struts per section (RUTSS) (R(2) = 0.24), whereas OFDI maintained superiority (R(2) = 0.66). In a more detailed analysis by OFDI, identification of individual uncovered struts demonstrated a sensitivity of 77.9% and specificity of 96.4%. Other important morphological features such as fibrin accumulation, excessive inflammation (hypersensitivity), and in-stent atherosclerosis were characterized by OFDI; however, the similarly dark appearance of these tissues did not allow for direct visual discrimination. The quantitative analysis of OFDI signal reflections from various in-stent tissues demonstrated distinct features of organized thrombus and accumulation of foamy macrophages.

CONCLUSIONS: The results of the present study reinforce the potential of OFDI to detect vascular responses that may be important for the understanding of long-term stent performance, and indicate the capability of this technology to serve as a diagnostic indicator of clinical success.

PMID: 22239896

Long-Term Follow-Up After Fractional Flow Reserve-Guided Treatment Strategy in Patients With an Isolated Proximal Left Anterior Descending Coronary Artery Stenosis

OBJECTIVES: This study sought to evaluate the long-term clinical outcome of patients with an angiographically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR). When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized.

METHODS: In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was ≥ 0.80, the patients (n = 564) were treated medically (medical group); when FFR was <0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population.

RESULTS: The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 ± 14% vs. 54 ± 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001).

CONCLUSIONS: Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR ≥ 0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population.

PMID: 22035875

Pulmonary Hypertension: How the Radiologist Can Help

Pulmonary hypertension is defined as an abnormal elevation of pressure in pulmonary circulation, with a mean pulmonary arterial pressure higher than 25 mmHg, regardless of the underlying mechanism. The clinical classification system for pulmonary hypertension was updated at the fourth World Symposium on Pulmonary Hypertension in Dana Point, California, in 2008. In patients with suspected pulmonary hypertension, the diagnostic approach includes four stages: suspicion, detection, classification, and functional evaluation. It is crucial to understand the advantages and disadvantages of the different imaging tools available for the diagnostic work-up and follow-up of patients with pulmonary hypertension. Many conditions that cause pulmonary hypertension have suggestive findings at multidetector computed tomography or magnetic resonance imaging; some causes may be surgically treatable, whereas others may demonstrate adverse reactions to vasodilator therapies used during the course of treatment. Therefore, the radiologist plays an important role in evaluating patients with this disease.

PMID: 22236891

Infarct Detection With a Comprehensive Cardiac CT Protocol

OBJECTIVES: Cardiac CT has the potential to offer comprehensive infarct detection by assessing regional wall motion abnormalities (RWMAs), rest perfusion defects (RPDs), and delayed contrast enhancement (DCE). However, the diagnostic accuracy of these techniques for the detection of myocardial infarction (MI) is unknown.

METHODS: Forty-eight patients with intermediate-to-high probability for coronary artery disease after single-photon emitting CT myocardial perfusion imaging were prospectively enrolled for a research comprehensive 64-detector row dual-source cardiac CT protocol that included cine images for RWMA, first-pass images for RPD, and delayed images for DCE. Blinded readers independently assessed each technique. Subsequently, a final combined analysis (cine + rest + DCE) was performed. The universal definition for MI by the 2007 American Heart Association task force was used as the “gold standard.”

RESULTS: Twenty-four of 48 patients (50%) had infarct by the universal definition. The combined CT analysis was most accurate (90%) with the highest per-patient sensitivity (88%) and specificity (92%) versus individual assessments (RWMA, 79% and 88%; RPD, 67% and 92%; DCE, 79% and 88%). Similar findings were observed on a per-vessel basis analysis. A combination of DCE and cine showed a good accuracy (85%) and high sensitivity (92%).

CONCLUSIONS: Infarct detection with CT is feasible with overall good diagnostic accuracy compared with the universal definition. A combined evaluation that included all techniques (cine, RPD, and DCE) had the highest diagnostic accuracy. These findings may have implications when designing future clinical and research CT protocols for optimal infarct detection.

PMID: 22210535

Assessment of Valvular Calcification and Inflammation by Positron Emission Tomography in Patients With Aortic Stenosis

OBJECTIVES: The pathophysiology of aortic stenosis is incompletely understood and the relative contributions of valvular calcification and inflammation to disease progression are unknown.

METHODS: Patients with aortic sclerosis and mild, moderate and severe stenosis were prospectively compared to age and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by sodium 18-fluoride (18F-NaF) and 18-fluorodeoxyglucose (18F-FDG) uptake using positron emission tomography. One hundred and twenty one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG.

RESULTS: Quantification of tracer uptake within the valve demonstrated excellent inter-observer repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios (TBR). Activity of both tracers was higher in patients with aortic stenosis than control subjects (18F-NaF:2.87±0.82 vs 1.55±0.17; 18F-FDG: 1.58±0.21 vs 1.30±0.13; both P1.97) and 35% increased 18F-FDG (>1.63) uptake. A weak correlation between the activities of these tracers was observed (r(2)= 0.174, P

CONCLUSIONS: Positron emission tomography is a novel, feasible and repeatable approach to thee valuation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlates with disease severity, and is strongest for 18F-NaF.

PMID: 22090163

Computed Tomography Stress Myocardial Perfusion Imaging in Patients Considered for Revascularization: A Comparison With Fractional Flow Reserve

PMID: 21810860

Iterative Reconstruction of Dual-Source Coronary CT Angiography: Assessment of Image Quality and Radiation Dose

OBJECTIVES: To assess the image quality and radiation dose of low-dose dual-source CT (DSCT) coronary angiography reconstructed using iterativereconstruction in image space (IRIS), in comparison with routine-dose CT using filtered back projection (FBP).

METHODS: Eighty-one patients underwent low-dose coronary DSCT using IRIS with two protocols: (a)100 kVp and 200 mAs per rotation for body mass index (BMI) < 25 (group I), (b)100 kVp and 320 mAs for BMI ≥ 25 (II). For comparison, two sex-and BMI-matched groups using standard protocols with FBP were selected: (a)100 kVp and 320 mAs for BMI < 25 (III), (b)120 kVp and 320 mAs for BMI ≥ 25 (IV). Image noise, signal to noise ratio (SNR) and modulation transfer function (MTF) 50% were objectively calculated. Two blinded readers then subjectively graded the image quality. Radiation dose was also measured.

RESULTS: Image noise tended to be lower in IRIS of low-dose protocols: 22.0 ± 4.5 for group I versus 24.8 ± 4.0 for III (P < 0.001); 20.9 ± 4.5 for II versus 21.6 ± 4.9 for IV (P = 0.6). SNR was better with IRIS: 25.8 ± 4.4 for I versus 22.7 ± 4.6 for III (P < 0.001); 24.6 ± 5.4 for II versus 18.7 ± 4.5 for IV (P < 0.001). No differences in MTF 50% or image quality scores were seen between each two groups (P > 0.05). Radiation reduction was 40% for I and 51% for II, compared to standard protocols.

CONCLUSIONS: Compared with routine-dose CT using FBP, low-dose coronary angiography using IRIS provides significant radiation reduction without impairment to image quality.

PMID: 22187198

A High-Risk Period for Cerebrovascular Events Exists After Transcatheter Aortic Valve Implantation

OBJECTIVES: This study assesses if there exists a high-risk period for cerebrovascular events (CeV) after transcatheter aortic valve implantation (TAVI). Even though acute strokes after TAVI have been described, it is uncertain if stroke rates continue to remain high in the early months after TAVI. Furthermore, the optimal dose and duration of thromboprophylaxis is unclear.

METHODS: Patients who underwent TAVI were evaluated at baseline, at discharge, at 1 and 6 months, and yearly. Risk factors for CeV events, procedural details, and antithrombotic therapy were recorded. Outcomes assessed were CeV events and death. The timing of such events, predictors, and impact on survival were analyzed.

RESULTS: A total of 253 patients were assessed. Median age was 85 years. The median Society of Thoracic Surgeons score was 8.1% (interquartile range [IQR]: 5.5% to 12.0%). Risk factors included smoking (47%), hypertension (70%), dyslipidemia (66%), and diabetes mellitus (25%). Twenty-three percent had known cerebrovascular disease and 39% had atrial fibrillation. Median follow-up was 455 days (IQR: 160 to 912 days) at which time 23 patients experienced a CeV event. The incidence was highest in the first 24 h but remained high for 2 months. In-hospital mortality rate after a CeV event was 21%. A prior history of CeV disease was an independent predictor of an event (hazard ratio: 4.23, 95% CI: 1.60 to 11.11, p = 0.004).

CONCLUSIONS: The incidence of CeV events is highest within 24 h of TAVI, but this risk may remain elevated for up to 2 months. A prior history of cerebrovascular disease is an independent predictor. This may have implications for patient selection and antithrombotic strategies.

PMID: 22192370

Anomalous Origin of the Right Coronary Artery from the Left Coronary Sinus With an Interarterial Course: Subtypes and Clinical Importance

OBJECTIVES: To classify anomalous origins of the right coronary artery (RCA) from the left coronary sinus (AORL) with an interarterial course into two subtypes and to evaluate the clinical importance of each.

METHODS: Institutional review board approval was obtained for this retrospective study, and informed consent was waived. Through a retrospective review of 22 925 consecutive cardiac computed tomographic (CT) scans, 124 cases of AORL with an interarterial course were identified. These anomalies were classified into two subtypes according to the location of the anomalous RCA ostium: high interarterial course (between the aorta and the pulmonary artery) and low interarterial course (between the aorta and the right ventricular outflow tract). The clinical records were evaluated, and differences in prevalence of typical angina and major adverse cardiac events (MACEs) between the subtypes were analyzed through the χ(2) contingency tables or Fisher exact test.

RESULTS: After excluding patients with combined cardiac disease, 87 patients (51 [59%] men, 36 [41%] women; mean age, 56.0 years) were enrolled. Of the 87 patients, 53 had a high interarterial course and 34 had a low interarterial course. A significant difference in the prevalence of typical angina (high [43%] vs low [6%], P = .001) and MACE (high [28%] vs low [6%], P = .012) was observed between the two subtypes. For patients with a high interarterial course, the odds ratio for typical angina was 12.3 (95% confidence interval: 2.7, 56.6), and the odds ratio for MACE was 6.3 (95% confidence interval: 1.3, 29.7).

CONCLUSIONS: The prevalence of typical angina and that of MACE were significantly higher in patients with a high interarterial course than in those with a low interarterial course.

PMID: 22056684