Imaging excerpts from scientific meetings |
Imaging Highlights From the European Society of Cardiology, American Society of Nuclear Cardiology, and Heart Failure Society of America
Juhani Knuuti, MD, PhD*,
Don Poldermans, MD, PhD ,
James E. Udelson, MD ,
Frans J. Th. Wackers, MD, PhD, FACC ,
Jeroen J. Bax, MD, PhD, FACC||,1,*
* Turku PET Center, Turku, Finland
ThoraxCenter, Rotterdam, the Netherlands
Tufts–New England Medical Center, Boston, Massachusetts
Yale University School of Medicine, New Haven, Connecticut
|| Leiden University Medical Center, Leiden, the Netherlands.
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Abstract
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Cardiac imaging has become an integrated part in the diagnostic and prognostic work-up of patients with cardiovasular disease. In this article, highlights of scientific abstracts on cardiac imaging presented at the European Society of Cardiology (ESC), the American Society of Nuclear Cardiology (ASNC), and the Heart Failure Society of America (HFSA) are summarized.
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ESC 2007
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The ESC meeting was held in Vienna, Austria, from September 1 to 5, 2007. The total attendance of the meeting was close to 30,000; more than 3,500 abstracts were selected for presentation, with more than 400 dedicated to cardiac imaging.
A variety of echocardiographic studies were presented focusing on their diagnostic and prognostic role in ischemic heart disease and heart failure, especially using new ultrasound techniques.
Echocardiographically determined CFR.
Sicari et al. (1) presented data from a multicenter study on the prognostic value of coronary flow reserve (CFR) of the left anterior descending coronary artery as assessed during dipyridamole stress using color Doppler flow mapping. A total of 1,506 patients with known or suspected coronary artery disease (CAD) were included, CFR was assessed (>2 was considered normal), and patients were followed up for a median period of 42 months. In total, 74 cardiac events occurred, with 24 deaths and 50 nonfatal myocardial infarctions. Survival of patients with normal CFR was excellent (Fig. 1) compared with those with reduced CFR. The same investigators in 1,130 diabetic patients with a normal stress test demonstrated that an abnormal CFR identified a subpopulation at increased risk (2). During a median follow-up of 16 months, 98 cardiac events occurred (8 deaths, 90 myocardial infarctions). Using multivariable analysis, an abnormal CFR was associated with a hazard ratio of cardiac death or infarction of 4.95 (95% confidence interval [CI] 3.3 to 7.5). The CFR measurements were also performed in a study focusing on patients with syndrome X (defined as having a positive exercise test result with normal coronary arteries on invasive angiography) (3), wherein a total of 185 patients were compared with a matched population with normal exercise test results. In all patients and matched controls, left ventricular (LV) contractility (systolic blood pressure/LV end-systolic volume index) was measured and CFR from the left anterior descending coronary artery was determined at rest and during peak stress (dipyridamole). Patients with syndrome X had comparable LV contractility but a significantly lower CFR as compared with controls (2.5 ± 0.5 vs. 3.2 ± 0.4, p < 0.001). The ratio of LV contractility to CFR was defined as the contractility perfusion index, which was significantly higher in syndrome X because of the lower CFR.
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Figure 1 Kaplan-Meier Event-Free Survival Curves
Kaplan-Meier event-free survival curves of patients with normal coronary flow reserve (CFR) (>2) and reduced CFR. Data from Sicari et al. (1).
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Stress echocardiography.
Another study focused on the relation between transient dobutamine-induced myocardial ischemia and the inflammatory response (4). In 106 patients undergoing dobutamine stress echocardiography, interleukin-6 release was measured at rest and stress. Patients were followed up for 63 ± 20 months for occurrence of the composite end point of cardiac death, nonfatal infarction, and unstable angina. Patients with events had a significantly higher interleukin-6 release during peak stress (3.3 pg/ml vs. 2.1 pg/ml, p = 0.02). Optimal prognostic information was derived from integration of peak interleukin-6 levels and ischemia during stress echocardiography. Aggeli et al. (5) presented data on the safety of stress echocardiography combined with intravenous myocardial contrast administration in 5,450 patients (71% men, mean age 65 ± 11 years). This combination permits integrated assessment of wall motion and myocardial perfusion during stress echocardiography, possibly increasing accuracy for detection of CAD. In all patients, a 1- to 1.5-ml bolus of contrast was administered at rest and peak stress. No death or infarction occurred during the test; cardiac arrhythmias (ventricular and supraventricular) occurred in 30 of 5,450 patients (0.55%). Other side effects included headache in 54 (0.99%) and vagal reaction with hypotension in 41 (0.75%) patients.
Echocardiography in resynchronization.
In addition to ischemic heart disease, many abstracts were presented on the use of echocardiography in cardiac resynchronization therapy (CRT). Because 20% to 30% of patients do not respond to CRT, the search for improved selection continues. Two-dimensional radial strain with speckle-tracking technology was used to predict response to CRT in 116 drug-refractory heart failure patients (New York Heart Association [NYHA] functional class III to IV) with depressed LV ejection fraction (<35%) and wide QRS complex (>120 ms) (6). Left ventricular dyssynchrony was evaluated from the midventricular short-axis images and was calculated as the difference in time to peak systolic strain between anteroseptal and posterior regions (Fig. 2). Among 108 patients who completed the 6-month follow-up period, 59 (55%) showed response to CRT, assessed by an improvement in clinical status (NYHA functional class, quality-of-life score, and 6-min walking distance). The extent of LV dyssynchrony, expressed as the anteroseptal-to-posterior wall delay, was significantly larger in responders as compared with nonresponders (263 ± 152 ms vs. 139 ± 126 ms, p < 0.001). The optimal cutoff value to predict response to CRT was identified as an anteroseptal-to-posterior wall delay  130 ms, yielding a sensitivity of 83% with a specificity of 71% (Fig. 3). On the other hand, Rizzello et al. (7) suggested that myocardial viability could be a determinant of CRT response. In 21 patients undergoing CRT, myocardial viability was assessed using dobutamine stress echocardiography. Dysfunctional segments that showed improved wall motion during low-dose dobutamine infusion were classified as viable. Responders (n = 14) to CRT were those patients with an improvement in NYHA functional class after 6 months of CRT; responders showed an increase in LV ejection fraction from 25 ± 6% to 38 ± 7% (p < 0.01), which remained unchanged in nonresponders (24 ± 6% vs. 26 ± 5%, p = not significant). There was a direct correlation between the number of viable segments on dobutamine stress echocardiography and the change in LV ejection fraction after CRT. Using receiver operator characteristic curve analysis, the presence of 4 or more viable segments on dobutamine stress echocardiography best predicted response to CRT.
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Figure 2 Assessment of LV Dyssynchrony From 2-Dimensional Radial Strain Using Speckle Tracking
In the left panel, the 2-dimensional strain images are represented. The right panel shows the segmental time-strain curves for each region (the colors of the curves correspond to the colors of the regions on the short-axis slice in the left panel). Time differences in peak systolic strain (t) between anteroseptal (AS) and posterior (P) segments are measured and indicate the maximum dyssynchrony. Data from Delgado et al. (6).
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Figure 3 Accuracy of 2-Dimensional Radial Strain to Predict Response to Resynchronization Therapy
The receiver-operator characteristic curve analysis identified an optimal cutoff value to predict response to cardiac resynchronization therapy of 130 ms or more for left ventricular dyssynchrony reflected by an AS-to-P (AS-P) wall delay in 2-dimensional radial strain (RS). This cutoff value yielded a sensitivity of 83% with a specificity of 71%, with an area under the curve (AUC) of 0.75. Abbreviations as in Figure 2. Data from Delgado et al. (6).
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Magnetic resonance imaging (MRI) in CAD.
Various studies with MRI focused on the detection of CAD. Cheng et al. (8) evaluated 61 patients with first-pass perfusion MRI; stress was performed with adenosine. A direct comparison between 1.5- and 3-T MRI also was performed. Considering stenosis 50% on invasive angiography as the gold standard, a higher sensitivity (98% vs. 90%) and specificity (76% vs. 67%) were obtained with 3-T imaging as compared with 1.5-T, suggesting that the use of a higher magnetic field could improve the accuracy of perfusion imaging with MRI. Another MRI study reported on noninvasive angiography with whole-heart MRI in 58 patients (9); comparison was performed with multidetector computed tomography (MDCT) and invasive coronary angiography (Fig. 4). The MRI failed in 12% of patients, whereas MDCT was successfully completed in all patients. Among the remaining patients, the sensitivity of MRI angiography was 82% with a specificity of 78% to detect significant CAD (corresponding values for MDCT were 98% and 94%). In addition to the diagnostic studies, the prognostic value of MRI was evaluated in 420 patients who underwent stress-perfusion MRI, followed by delayed contrast-enhanced imaging (10). This way, resting function, stress function and stress perfusion, and scar tissue could simultaneously be assessed. Over a median follow-up of 420 days, 41 major events occurred (9 deaths, 14 infarctions, 18 episodes of unstable angina). Events were more frequent in patients with abnormal wall motion at rest (22% vs. 5%) or abnormal wall motion during stress (21% vs. 4%) and with perfusion defects during stress (17% vs. 5%); also events were more often found in patients with scar tissue according to delayed contrast-enhanced imaging (20% vs. 6%). In a multivariate analysis, abnormal wall motion during stress (dipyridamole) was the only MRI index that was independently related to major cardiac events.
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Figure 4 MRI, MDCT, and Invasive Coronary Angiography
Example of whole-heart MRI angiography (left), MDCT angiography (middle), and invasive angiography (right). Upper row = left coronary artery; lower row = right coronary artery. MDCT = multidetector computed tomography; MRI = magnetic resonance imaging. Data from Pouleur et al. (9).
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Incremental utility of computed tomography.
Numerous abstracts on the use of noninvasive angiography with MDCT were presented in the ESC meeting. Burgstahler et al. (11) evaluated the diagnostic accuracy of the new dual-source computed tomography (CT) scanner (with improved temporal resolution of 83 ms) for detection of significant stenoses in 41 patients with high pre-test likelihood of CAD and high calcium scores. As compared with invasive angiography, the positive predictive value was modest (70%) with a high negative predictive value (96%). The main reason for the false-positive results was an overestimation of calcified lesions (Fig. 5). Thus, accurate evaluation of patients with high calcium scores remains difficult even with the newest generation CT scanners. An issue with MDCT remains that the technique provides excellent anatomical information, but the hemodynamic consequences (induction of ischemia) of the lesions are not assessed. To better understand the relation between ischemia, atherosclerosis, and luminal narrowing, Schuijf et al. (12) performed a head-to-head comparison in 62 patients between single-photon emission computed tomography (SPECT) perfusion imaging, MDCT, invasive quantitative coronary angiography (QCA), and intravascular ultrasound (IVUS). Good agreement between the modalities was observed in patients with abnormal SPECT. However, a normal SPECT study was frequently (82%) associated with an abnormal MDCT despite only minimal luminal stenosis on QCA (26.0 ± 16.8%). Further evaluation by IVUS in these patients revealed the presence of considerable plaque burden (57.9 ± 18.2%), yet without luminal compromise (average minimal luminal area 5.9 ± 3.4 mm2). These observations underscore that atherosclerosis on MDCT may frequently not result in ischemia; in these patients, the detected atherosclerosis may be located mainly in the vessel wall, rather than extending into the coronary lumen. Another study focused on the relative merits of SPECT perfusion imaging and MDCT for long-term prognosis (13). In a multicenter trial, 352 patients with known or suspected CAD were enrolled and underwent both SPECT and MDCT imaging; events were recorded over a mean follow-up of 15 months. The MDCT was abnormal in 73% of patients, whereas SPECT was abnormal in 41%. The lowest event rates were observed in patients with normal MDCT and SPECT, whereas patients with abnormal MDCT and SPECT had the highest event rates. Intermediate event rates were observed in patients with normal SPECT but abnormal MDCT (Fig. 6).
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Figure 5 Dual-Source MDCT Study in a Patient With Severe Coronary Calcifications
Arrows denote the vessel segment with severe coronary calcifications (making interpretation difficult) but lumen narrowing on the invasive angiography. Abbreviations as in Figure 4. Data from Burgstahler et al. (11).
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Figure 6 Prognosis According to MDCT and SPECT Perfusion Imaging
Cardiac event rate (cardiac death, nonfatal infarction, unstable angina requiring hospitalization, and late revascularization) according to MDCT and SPECT data. MPI = myocardial perfusion imaging; SPECT = single-photon emission computed tomography; other abbreviations as in Figure 4. Data from Van Werkhoven et al. (13).
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Advances in SPECT and PET tracers.
Several studies addressed the role of positron emission tomography (PET) for perfusion imaging; PET is still the only technique that permits absolute quantification of physiological processes, such as myocardial perfusion. Askew et al. (14) compared 2 PET perfusion tracers, O15-labeled water and N13-ammonia, in a swine model of acute myocardial infarction. Perfusion, as assessed by both tracers, correlated well with microspheres. Because both O15 and N13 isotopes have a short half-life, a new perfusion tracer (BMS-747158-02) has recently been developed that is labeled with F18 and has a much longer half-life (15). The longer half-life makes transportation over longer distances possible, permitting use in PET centers that do not have a cyclotron on site. In a pig model, homogenous uptake of this new tracer was shown, with a slight improvement in image quality as compared with N13-ammonia because of more specific cardiac uptake and lesser background activity (Fig. 7). Another field of interest is cardiac innervation imaging; I-123 metaiodobenzylguanidine is a SPECT tracer (epinephrine analogue) that was used in 42 patients with arrhythmogenic right ventricular cardiomyopathy (16). It was shown that an impairment of adrenergic innervation was associated with higher risk for sustained and recurrent ventricular tachycardias, suggesting a potential role of I-123 metaiodobenzylguanidine imaging for risk stratification in these patients.
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Figure 7 Comparison of Image Quality of F18-BMS-747158-02 and N13-Ammonia Perfusion Studies in a Healthy Normal Pig
Image acquisition was performed sequentially on an LSO-positron emission tomography scanner (200 MBq NH3 first, 30-min delay, 100 MBq BMS second; 5-min post-injection; scan duration 5 min for both tracers). LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle. Data from Nekolla et al. (15).
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ASNC 2007
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The 12th annual scientific session of the ASNC was held in San Diego, California, from September 6 through 9, 2007. The meeting, entitled "Cardiac Imaging: Imagine the Future," attracted over 1,700 attendees. A total of 83 abstracts in the field of nuclear cardiology and cardiac CT were presented.
Technological and procedural improvements in SPECT perfusion imaging.
Pena et al. (17) reported on wide beam reconstruction (WBR) technology, which is a novel iterative SPECT reconstruction method that suppresses image noise and improves image resolution without post-filtering as used in conventional filtered back projection (FBP). The investigators compared these 2 techniques in 100 patients. Two sets of gated SPECT images were obtained, 1 with conventional acquisition time and FBP and a second set with shorter acquisition time and WBR. With WBR, overall image quality was better than with FBP, whereas diagnostic information (defect size, LV volumes, and ejection fraction) was similar (Fig. 8). This and other novel reconstruction methodologies have substantial promise for improving SPECT imaging. Corbett et al. (18) evaluated the diagnostic performance of a commercial CT-based attenuation correction SPECT system in comparison to noncorrected SPECT imaging for detecting CAD in 166 patients. Invasive coronary angiography was used as the gold standard. Sensitivity, specificity, and accuracy all increased significantly when CT-based attenuation correction was used, both on a patient and a vessel basis (Table 1). The impact of myocardial viability and scar formation on the response to CRT was evaluated by Feng et al. (19). Thirty patients with ischemic cardiomyopathy undergoing CRT were studied with PET and F18-fluorodeoxyglucose. The patients who responded favorably to CRT had more viable segments and less extensive scar formation. The assessment of scar tissue/viability on PET imaging could possibly be integrated with assessment of LV dyssynchrony on echocardiography to permit optimal prediction of response to CRT.
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Figure 8 Reconstruction of SPECT Perfusion Data: WBR Versus FBP
Correlation of summed stress score (SSS) derived from images processed with conventional filtered back projection (FBP) acquired over 30 stops, 40 s/stop (total 20 min) and images processed with wide-beam reconstruction (WBR) technology acquired over 60 stops, 10 s/stop (total acquisition time 10 min). An excellent correlation is observed between these 2 techniques over a wide range of SSS. SPECT = single-photon emission computed tomography. Data from Pena et al. (17).
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Cardiac computed tomography in anatomically and physiologically significant CAD.
A meta-analysis of the published studies with 64-slice multislice computed tomography, including 680 patients and 11,562 segments, revealed a sensitivity of 86% with a specificity of 97% on a segment basis for detection of CAD as compared with invasive angiography. On a patient basis, the sensitivity was 97% with a specificity of 91% (20). Brooks et al. (21) compared the appropriateness of the clinical use of SPECT and MDCT according to published American College of Cardiology/ASNC appropriateness criteria. Data from a single center were evaluated, including 1,209 SPECT perfusion studies and 133 CT angiography studies. The were significantly more appropriate SPECT studies as compared with CT studies (78% vs. 38%, p < 0.01), but also significantly more CT studies labeled as uncertain as compared with SPECT studies (18% vs. 6%, p < 0.01). These results underscore that the precise clinical position of CT angiography is not entirely clear. Altman et al. (22) evaluated the ability of 64-slice CT angiography to detect physiologically significant lesions, that is, associated with abnormal stress SPECT images. In 59 patients with an intermediate pre-test likelihood of CAD, a normal CT angiogram was generally associated with a normal SPECT study (96% of cases). Conversely, significant stenoses (50% luminal narrowing) on CT angiography were associated with an abnormal SPECT in only 40% of cases (Fig. 9). These findings again underscore that stenoses on CT angiography do not necessarily translate in ischemia. To overcome these problems, the use of PET-CT may be of interest, but the high radiation dose of the combined modalities is a drawback. With the newest CT technology, data acquisition is performed by prospective gating and the step-and-shoot technique. Kajander et al. (23) evaluated 10 patients with this new technology and compared the image quality with routine CT equipment. The image quality of the noninvasive angiograms was comparable, but a reduction in radiation dose with the new technology of 60% was demonstrated. There is concern that noncalcified, nonobstructive plaques on MDCT may potentially represent vulnerable lesions. Sato et al. (24) evaluated the prognostic value of low-density (<68 HU) plaques in nonobstructive (25% to 75%) coronary artery stenoses detected on MDCT in 810 consecutive patients. These lesions were identified in 189 patients. The cardiac event rate (acute myocardial infarction, unstable angina) during a follow-up period of 1,060 ± 539 days was 3%. The presence of low-density plaques in nonobstructive stenoses was the sole independent predictor of future cardiac events (Fig. 10).
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Figure 9 Relationship Between Findings on 64-Slice CTA and Stress SPECT MPI on a Patient Basis
Of 44 patients without significant coronary artery stenoses on computed tomography coronary angiography (CTA), stress myocardial perfusion imaging (MPI) was normal in 91%. Of 15 patients with apparent significant stenoses (50%) on CTA, stress MPI was abnormal in 60%. SPECT = single-photon emission computed tomography. Data from Brooks et al. (21).
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Figure 10 Event-Free Survival Versus Soft Plaques on MDCT
Cumulative survival, free of acute coronary syndrome (ACS), in 810 patients with nonobstructive coronary artery disease on computed tomography angiography with (Group 1, n = 189) and without (Group 2, n = 621) low-density (<68 HU) coronary plaques. Abbreviations as in Figure 4. Data from Sato et al. (24).
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HFSA 2007
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The 11th Annual Scientific Sessions of the HFSA were held in Washington, DC, September 16 through 19, 2007. The meeting attracted 2,750 attendees, and 401 abstracts were presented pertaining to clinical and basic science in heart failure. Only a few abstracts highlighted the role of imaging in heart failure. Echocardiography remains the most important tool in evaluation of heart failure. The recent technological advances allow a precise evaluation of myocardial mechanics including velocity vectors and development of strain. Rajagopalan et al. (25) evaluated 63 patients with right ventricular strain with echocardiography and compared the findings with invasive hemodynamic measurements. Right ventricular strain correlated significantly with transpulmonary gradient, pulmonary vascular resistance, and cardiac index. Reeves et al. (26) used handheld echocardiography with tissue Doppler imaging to noninvasively estimate cardiac filling pressures. With the availability of this sophisticated technology on handheld echocardiography equipment, the use of echocardiography in intensive care settings to noninvasively monitor the hemodynamic status of heart failure patients will increase further.
Several studies also reported on the use of noninvasive imaging to assess cardiac dyssynchrony in heart failure patients because dyssynchrony may be an important predictor of response to CRT. Building on methodology used in radionuclide ventriculography over 20 years ago, Trimble et al. (27) presented several abstracts highlighting various aspects of the use of gated SPECT perfusion imaging to assess dyssynchrony by incorporating phase analysis. This technique utilizes a 3-dimensional, count-based Fourier analysis method to convert the regional myocardial counts from discrete frames per cardiac cycle into a continuous thickening function that allows quantification of the phase of the onset of myocardial contraction and its temporal dispersion. The dispersion of phases obtained throughout the LV is a measure of dyssynchrony and is displayed in histogram format, and expressed as the standard deviation (SD) of phase values around the entire LV; histogram bandwidth is yet another parameter reflecting dyssynchrony. Figure 11
shows 2 representative phase histograms from patients with LV ejection fraction  35%, with varying levels of dyssynchrony. In another study, these investigators reported on a higher prevalence of cardiac dyssynchrony in patients with ischemic cardiomyopathy as compared with nonischemic cardiomyopathy (28). The investigators evaluated 125 patients with heart failure, including 98 with ischemic and 27 with nonischemic cardiomyopathy. Both phase SD (49.3° vs. 28.0°, p < 0.01) and bandwidth (138.7° vs. 88.9°, p < 0.01) were larger in ischemic cardiomyopathy patients (reflecting more dyssynchrony). In a third study (29), these investigators showed that patients with prolonged QRS duration have, on average, higher degrees of dyssynchrony than patients with normal QRS duration as measured by the phase SD. Still, 38% of patients with LV ejection fraction 35% and normal QRS duration had substantial evidence of dyssynchrony. The potential advantage of this phase analysis technique is the automated assessment of global dyssynchrony, and for coupling this information to information on LV ejection fraction, volumes, ischemia, and viability obtained with gated SPECT. Hatchcock et al. (30) used echocardiography with tissue Doppler imaging to assess LV dyssynchrony and predict response to CRT in heart failure patients with a narrow QRS complex. Patients with LV dyssynchrony (n = 15) responded favorably to CRT, whereas patients without dyssynchrony did not. Of note, the benefit (in terms of LV reverse remodeling and improvement in LV ejection fraction) was similar in patients with wide and narrow QRS complex and LV dyssynchrony. Another study reported on the use of echocardiographically optimized settings in CRT. With the newer devices, optimization of the interventricular pacing interval is feasible, and MacCarter et al. (31) demonstrated an improvement in oxygen uptake efficiency after echocardiography-guided optimization. Another final topic of interest was the use of stem cells in heart failure. One study reported on the use of gated SPECT imaging to evaluate LV ejection before and after autologous bone marrow mononuclear cells transplantation (32). In 12 patients undergoing cell transplantation, NYHA functional class improved significantly at 1-year follow-up associated with a 5% improvement in LV ejection fraction.
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Figure 11 Two Representative Phase Histograms From Patients With Left Ventricular Ejection Fraction 35%
For each, the left panel is a polar map representing the phase values around the left ventricle, and the right panel is a histogram of phase values. (B) Histogram shows a higher level of dyssynchrony as evidenced by a broader and less peaked phase histogram than seen in panel A. Data from Trimble et al. (27).
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Conclusions
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Imaging is an integral part of the management of cardiovascular disease, and the advances are occurring at a tremendous pace in all imaging modalities. A comparison of the imaging abstracts presented at the 3 conferences discussed herein shows that subspecialty conferences such as those of the Heart Failure Society, Electrophysiology and Pacing Society, and Heart Valve Society should encourage sessions devoted to advances in imaging. A stronger interaction is needed between the imagers and the subspecialty physicians to maximize the potential assets of various imaging modalities for superior diagnosis and management of cardiovascular disease.
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Footnotes
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1 Dr. Bax has research grants from Bristol-Myers Squibb Medical Imaging, GE Healthcare, St. Jude, Medtronic, and Boston Scientific. 
* Reprint requests and correspondence: Dr. Jeroen J. Bax, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. (Email: j.j.bax{at}lumc.nl).
Manuscript received October 17, 2007;
accepted October 23, 2007.
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Abstract
ESC 2007