ACC 2006 ANNUAL SESSION HIGHLIGHTS
Diagnostic Testing
Raymond J. Kim, MD, FACC*
Duke Cardiovascular Magnetic Resonance Center, Duke University, Durham, North Carolina.
* Reprint requests and correspondence: Dr. Raymond J. Kim, Duke Cardiovascular Magnetic Resonance Center, DUMC–Box 3934, Durham, North Carolina 27710. (Email: Raymond.kim{at}duke.edu).
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Abbreviations and Acronyms
| | 2D = two-dimensional | | 3D = three-dimensional | | AGES-Reykjavik = Age, Gene/Environment Susceptibility-Reykjavik trial | | CAD = coronary artery disease | | CMR = cardiovascular magnetic resonance | | CT = computed tomography | | DE-CMR = delayed contrast-enhanced cardiovascular magnetic resonance | | ECG = electrocardiogram | | ICD = implantable cardioverter-defibrillator | | LBBB = left bundle branch block | | LV = left ventricular | | LVEF = left ventricular ejection fraction | | MADIT-II = Multicenter Automatic Defibrillator Implantation Trial-II | | MDCT = multidetector computed tomography | | MI = myocardial infarction | | PH = pulmonary hypertension | | PET = positron emission tomography | | SPECT = single-photon emission computed tomography |
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A total of 857 abstracts were submitted to the Diagnostic Testing category. Among these, 276 were accepted for presentation and comprised 17% of all presented abstracts at the ACC.06 Scientific Sessions. In addition, several other categories, such as heart failure, ischemia and infarction, congenital heart disease, and valvular disease, received numerous abstracts with a major focus on noninvasive imaging. Within the diagnostic testing category, the presented abstracts may be divided into five subgroups: cardiovascular magnetic resonance (CMR), cardiac computed tomography (CT), nuclear cardiology, echocardiography, and exercise stress testing. The highlights selected represent only a small fraction of the high-quality, important abstracts that were presented in this category.
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Cardiovascular magnetic resonance
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One theme that is growing in importance for this modality is the need to transition from pilot studies that involve small numbers of patients to larger population-based studies. One example of the latter was presented by Arai et al. (1), who evaluated the prevalence of recognized and unrecognized myocardial infarction (MI) in the ICELAND MI substudy of the Age, Gene/Environment Susceptibility (AGES-Reykjavik) study. The AGES-Reykjavik study is characterizing approximately 6,000 people 67 to 95 years of age under the aegis of the U.S. National Institute on Aging and the Icelandic Heart Association.
The substudy involved a random sample of 447 of the AGES-Reykjavik patients who underwent delayed contrast-enhanced cardiovascular magnetic resonance (DE-CMR) (1). The investigators found that the prevalence of MI was 9.4% according to hospital records but only 6.7% by electrocardiogram (ECG) analysis. In comparison, DE-CMR suggested a prevalence rate that was considerably higher at 22%. The investigators concluded that magnetic resonance imaging reveals a substantially higher overall prevalence of MI than predicted from the literature and that DE-CMR was significantly more sensitive in detecting infarction than clinical and/or ECG criteria. Although these results are quite provocative, an essential next step would be to provide evidence that unrecognized MI, as detected by DE-CMR, has prognostic significance.
Given the relative infancy of CMR, there is a paucity of studies regarding its prognostic value. At this meeting, Dall’Armellina et al. (2) presented one such study reporting on the prognostic value of dobutamine stress CMR. The authors focused on a cohort of 240 patients who were not well suited for transthoracic echocardiography (i.e., poor echocardiographic windows) and were found at baseline to have resting left ventricular (LV) wall motion abnormalities. The finding of increasing LV dysfunction during dobutamine CMR was associated with adverse cardiac prognosis in terms of cardiac death or nonfatal MI after a mean follow-up time of 5 ± 1 years.
Already widely appreciated as clinically useful in assessing patients with ischemic heart disease, CMR, particularly DE-CMR, is emerging as a unique tool for the evaluation of nonischemic cardiomyopathies. Valente et al. (3) assessed the relationship between myocardial fibrosis detected by DE-CMR and diastolic function in patients with hypertrophic cardiomyopathy. They reported that the presence of hyperenhancement (fibrosis) was associated with earlier age of symptom onset, greater septal wall thickness, and several indices of diastolic dysfunction as measured by Doppler echocardiography. A restrictive filling pattern, for example, was observed in 35% of patients with hyperenhancement versus 7% in patients without hyperenhancement. The authors speculated that DE-CMR may provide insight into the pathogenesis of diastolic dysfunction in patients with hypertrophic cardiomyopathy.
Continuing the theme of new CMR applications, Sanz et al. (4) performed DE-CMR in 38 patients with known or suspected pulmonary hypertension (PH). In these patients, who also underwent right heart catheterization on the same day, hyperenhancement (fibrosis) frequently was evident in a peculiar location: in the anterior and inferior ventricular septum where the right ventricular free wall inserts.
This unusual pattern is distinct from that typically observed in patients with coronary artery disease (CAD) and previous MI. This non–CAD-type pattern identified the presence of PH with a sensitivity and specificity of 94% and 86%, respectively. Moreover, the extent of hyperenhancement was correlated significantly, with the mean pulmonary artery pressure measured invasively. The authors concluded that hyperenhancement of the ventricular septum at the right ventricular insertion points is common in PH and the extent of hyperenhancement is related to the severity of PH.
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Computed tomography
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The potential clinical roles of multidetector computed tomography (MDCT) was a central theme. Raff et al. (5) examined the utility of MDCT in 200 patients with low-risk acute chest pain. Patients were assigned randomly to either immediate 64-slice CT coronary angiography or standard-of-care evaluation (radionuclide stress testing). Patients undergoing CT angiography were discharged for luminal stenosis <25%, referred to invasive X-ray angiography for stenosis >70%, and crossed over to stress testing for intermediate lesions or if the CT examination was uninterpretable.
There was no difference in 90-day major adverse coronary event rates for either the CT angiography or standard-of-care strategies. However, patients undergoing CT angiography had a 43% shorter length of stay (12.5 h vs. 22.1 h; p < 0.001) and a 15% lower cost of care ($1,586 vs. $1,872; p < 0.001). Of interest, more CT angiography patients underwent invasive coronary angiography (11 vs. 3), with the result that CT angiography correctly predicted catheterization results in 10 of 11 patients whereas standard-of-care predicted correct results in 2 of 3 patients. The authors concluded that CT angiography can rapidly and safely triage low-risk acute chest pain patients while reducing length of stay and cost of care.
In another evaluation of the utility of 64-slice MDCT, Rubinshtein et al. (6) studied 133 consecutive patients with chest pain and negative or equivocal exercise treadmill tests. multidetector CT identified obstructive CAD ( 50% stenosis) in 25% of the patients with negative exercise stress tests, whereas MDCT excluded CAD in more than one-half of those patients with equivocal exercise stress tests (Table 1). Invasive angiography confirmed the MDCT findings of obstructive CAD in 91% of patients. Thus, the conclusion was that MDCT appears to be an excellent tool for improving diagnostic accuracy in patients with chest pain, moderate pretest probability of CAD, and negative or equivocal findings on exercise stress testing.
A number of abstracts examined the safety of MDCT with regards to radiation exposure. Einstein et al. (7) sought to determine the effective radiation dose and lifetime attributable risk of cancer for patients undergoing coronary imaging using 16-slice MDCT. Effective radiation doses and organ equivalent doses were estimated by actual scan parameters and computer modeling, with lifetime attributable risk determined using models developed in the National Academies’ Biological Effects of Ionizing Radiation VII Report.
On average, the radiation dose was 9 mSv, which increased to 11.5 mSv when calcium scoring was included. Radiation doses were comparable with standard nuclear cardiology protocols (Fig. 1). Interestingly, the radiation dose was greater in women than in men (13.5 mSv vs. 11 mSv). The lifetime attributable risk of cancer incidence was estimated to be 1 in 1,600, with a worst-case scenario of 1 in 500. Most of this increased risk was due to lung cancer overall and breast cancer in women. The authors have initiated a similar analysis using 64-slice MDCT, and based on preliminary data, it appears the radiation dose will be approximately 50% higher.
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Figure 1 Effective doses in computed tomography angiography (CTA) and radionuclide imaging. Reprinted with permission (7).
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Nuclear cardiology
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In reviewing the nuclear imaging presentations, one notable theme was the growing popularity of hybrid imaging that combines myocardial perfusion imaging with coronary anatomy evaluation using MDCT. The rationale, of course, is that information regarding the presence or absence of myocardial ischemia is different and usually complementary to coronary anatomy. Di Carli et al. (8) studied 100 consecutive patients with low-to-intermediate pretest likelihood of CAD using hybrid imaging that combined stress positron emission tomography (PET) and MDCT (16- or 64-slice). There was a high negative predictive value with MDCT for identifying myocardial regions or patients with myocardial ischemia but, unfortunately, the positive predictive value was quite low (Table 2), only 26% on a per-vessel analysis and 42% on a per-patient analysis. Conversely, a normal stress PET examination was a poor discriminator of patients without subclinical coronary atherosclerosis, only 49% had normal CT angiography. Accordingly, the authors suggest a complementary role of MDCT and PET for optimizing post-test management decisions in patients with suspected CAD.
Integrated single-photon emission computed tomography (SPECT) with 16-slice MDCT was used in another study for the assessment of hemodynamically significant coronary lesions. Fifty-seven patients with chest pain underwent perfusion and anatomical imaging using an experimental SPECT/CT scanner followed by invasive coronary angiography (9). Hemodynamically significant lesions were defined as >50% stenosis by invasive coronary angiogram plus a reversible perfusion defect by SPECT in the same territory. Not surprisingly, the negative predictive value was quite high (98% for CT angiography alone; 99% for the SPECT/CT hybrid), but for CT angiography alone, the positive predictive value was quite low (31%) for predicting a hemodynamically significant lesion. However, the hybrid approach had a much higher positive predictive value (77%).
Prognostic studies have long been a staple in nuclear cardiology, and two studies offer interesting findings. Abidov et al. (10) studied 3,647 patients who underwent rest-stress dual isotope-gated SPECT. By multivariable analysis, after accounting for SPECT perfusion indices, both resting left ventricular ejection fraction (LVEF) (<35%) and a stress-induced decrease in LVEF (>5% change) were independent predictors of cardiac death (Fig. 2). Yoshinaga et al. (11) assessed the prognostic value of dipyridamole PET imaging in obese (n = 134) and nonobese (n = 233) patients. Patients were followed for 3.1 ± 0.9 years and evaluated for the primary combined end point of cardiac death and nonfatal MI. Obese patients (body mass index >30 kg/m2) with an abnormal PET summed stress score had a markedly greater event rate compared with those with a normal summed stress score (6% vs. 0% per year; p < 0.001). Each of the event rates for normal and abnormal stress score groups were not different between obese and nonobese patients.
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Figure 2 Adjusted cardiac survival curves based on resting left ventricular ejection fraction (LVEF) and stress-induced change in LVEF detected by single-photon emission computed tomography. Reprinted with permission (10).
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Echocardiography
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With the proliferation of new imaging tests, it is easy to forget the wealth of information that is provided by tried-and-true approaches such as standard transthoracic echocardiography. Zohlman et al. (12) performed an intriguing study regarding risk stratification of patients who are eligible for an implantable cardioverter-defibrillator (ICD). The authors retrospectively reviewed all patients at their center who had ICD placement from 1997 to 2005 and echocardiography within one year before or one week after implantation (12). Eighty-seven of the 156 patients identified met Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) criteria. In comparing a number of clinical indices (age, QRS width, blood pressure, LVEF, LV dimensions on echocardiography), there were no differences between those patients with and without ventricular events requiring ICD shock. However, the simple measurement of left atrial area, based on an apical four-chamber view, differentiated those requiring ICD therapy (30 cm2 vs. 25 cm2; p = 0.0004).
Jeetley et al. (13) studied intermediate-risk patients presenting to their center in the United Kingdom with chest pain who were troponin negative. Patients were assigned randomly to traditional exercise ECG (n = 218) or stress echocardiography (n = 215) as the first-line test. More patients in the stress echocardiography group were discharged home without further tests compared to the exercise ECG group (77% vs. 33%; p < 0.0001) with no difference in cardiac event rates at follow-up (9 ± 5 months). Moreover, there was a cost benefit in favor of stress echocardiography compared with exercise ECG ($364 vs. $518; p < 0.0001). The investigators concluded that stress echocardiography should be considered as the first-line test to investigate troponin-negative patients with acute chest pain.
A plethora of emerging technologies are advancing the field of echocardiography. Hayat et al. (14) reported on an interesting study using myocardial contrast echocardiography. The rationale of the study was based on the fact that SPECT perfusion abnormalities frequently are detected both at rest and during vasodilator stress in patients with left bundle branch block (LBBB), even in the absence of CAD. The authors, therefore, performed both dobutamine stress myocardial contrast echocardiography as well as sestamibi SPECT imaging in 24 patients with LBBB and normal coronaries on invasive angiography. Far more patients had a perfusion abnormality on SPECT imaging (n = 10) than on contrast echocardiography (n = 1). Among those with SPECT defects, interventricular septal wall thickness was significantly lower (p = 0.01) both in systole and diastole than those without such defects. The conclusion was that SPECT perfusion defects are common in patients with LBBB without CAD and without true perfusion defects as assessed by contrast echocardiography. The explanation appears to be a partial volume effect due to the thinner septal wall in these patients.
Another emerging technology is three-dimensional (3D) echocardiography. Many clinical decisions, such as ICD placement, are based on LVEF, but clinical two-dimensional (2D) echocardiography has wide confidence intervals. Thus, Chukwu et al. (15) evaluated 68 patients with prior MI or heart failure and an LVEF <40% as determined by routine clinical methods. They performed 2D and 3D echocardiography as well as CMR, all within 24 h. They found 3D echocardiography to be superior to 2D with smaller underestimation of volumes, higher correlation, and narrower limits of agreement when compared with the truth standard of CMR.
The same investigators then took a subgroup of patients (n = 28) who met MADIT-II study criteria for ICD placement. These patients were followed for a mean of 239 ± 73 days for adverse events (death, sustained ventricular fibrillation or tachycardia, and ICD discharge). Although this study was small, with only seven clinical events, it is intriguing that volume indices by 3D but not 2D echocardiography were associated with adverse events.
Several studies reported on the utility of speckle tracking by 2D echocardiography. One such study by Suffoletto et al. (16) assessed radial strain as determined by speckle tracking in 46 patients with heart failure and 15 control subjects. Although LV radial dyssynchrony is predictive of response to resynchronization therapy in heart failure patients with wide QRS, dyssynchrony in heart failure patients with narrow QRS is poorly understood. This study confirmed that patients with wide QRS heart failure had severe dyssynchrony; but patients with narrow QRS also were found to have significant dyssynchrony compared with control subjects. In addition, patients with narrow QRS were found to have a different contraction pattern than those with wide QRS.
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Exercise stress testing
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Finally, it is important to recognize that common, simple indices measured during routine exercise stress testing may provide as much information as more complex methodologies. In a study of 6,145 male veterans referred for exercise stress testing, Prakash et al. (17) studied the prognostic significance of systolic blood pressure response to exercise. Patients were followed for a mean of 6.2 years. After adjusting for multiple clinical and stress-test variables, an attenuated exercised induced increase in systolic blood pressure ( 40 mm Hg) was found to be an independent significant predictor of cardiovascular mortality.
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References
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1. Arai AE, Cao JJ, Sigurdsson S, et al. Prevalence of recognized and unrecognized myocardial infarctionthe ICELAND MI substudy to the AGES-Reykjavik study. (abstr) J Am Coll Cardiol 2006;47(Suppl A):137A.2. Dall’Armellina E, Morgan TM, Darty S, Hamilton CA, Hundley WG. Cardiovascular magnetic resonance identification of adverse cardiovascular prognosis in women versus men with known or suspected ischemic heart disease(abstr) J Am Coll Cardiol 2006;47(Suppl A):136A. 3. Valente AM, Brosnan R, Wagner A, et al. The influence of myocardial fibrosis by delayed enhanced MRI on left ventricular diastolic function in hypertrophic cardiomyopathy(abstr) J Am Coll Cardiol 2006;47(Suppl A):136A. 4. Sanz J, Dellogrottaglie S, Kariisa M, et al. Delayed contrast enhancement on cardiac magnetic resonance imaging in patients with pulmonary hypertension(abstr) J Am Coll Cardiol 2006;47(Suppl A):137A. 5. Raff GL, Gallagher MJ, O’Neill WW, et al. Immediate coronary artery computed tomographic angiography rapidly and definitively excludes coronary artery disease in low-risk acute chest pain(abstr) J Am Coll Cardiol 2006;47(Suppl A):114A. 6. Rubehshtein R, Halon DA, Gaspar T, et al. Usefulness of 64-slice multi detector computed tomography to improve diagnostic yield in patients with chest pain and negative or equivocal exercise treadmill tests(abstr) J Am Coll Cardiol 2006;47(Suppl A):114A. 7. Einstein AJ, Sanz J, Dellogrottaglie S, et al. Radiation dose and predictable cancer risk in multidetector-row computed tomography coronary angiography (CTCA)(abstr) J Am Coll Cardiol 2006;47(Suppl A):114A. 8. Di Carli MF, Dorbala S, Limaye A, et al. Clinical value of hybrid PET/CT cardiac imagingcomplimentary roles of multi-detector CT coronary angiography and stress PET perfusion imaging. (abstr) J Am Coll Cardiol 2006;47(Suppl A):115A. 9. Rispler S, Roguin A, Keidar Z, et al. Integrated SPECT/CT for the assessment of hemodynamically significant coronary artery lesions(abstr) J Am Coll Cardiol 2006;47(Suppl A):115A. 10. Abidov A, Rozanski A, Hayes SW, et al. Comparative value of resting left ventricular dysfunction response to stress as predictors of cardiac mortality in patients undergoing gated myocardial perfusion SPECT(abstr) J Am Coll Cardiol 2006;47(Suppl A):116A. 11. Yoshinga K, Chow BJW, Williams K, et al. Prognostic value of rubidium-82 perfusion positron emission tomography in patients with obesity(abstr) J Am Coll Cardiol 2006;47(Suppl A):115A. 12. Zohlman A, Croft LB, Mehta D, Goldman ME. Left atrial size can identify the highest risk multicenter automatic defibrillator implantation trial-II patients for ventricular arrhythmic events(abstr) J Am Coll Cardiol 2006;47(Suppl A):111A. 13. Jeetley P, Burden L, Stoukova B, Senior R. Stress echocardiography is more cost-effective than stress electrocardiography for risk stratification of troponin negative acute chest pain patientsprospective randomized controlled trial. (abstr) J Am Coll Cardiol 2006;47(Suppl A):112A. 14. Hayat SA, Dwivedi G, Lim TK, Jacobsen AN, Senior R. Reduced septal wall thickness not hypoperfusion is the cause of perfusion defects on single photon emission computed tomography in patients with left bundle branch block without coronary artery diseasecomparison with myocardial contrast echocardiography. (abstr) J Am Coll Cardiol 2006;47(Suppl A):131A. 15. Chukwu EO, Gopal AS, Dim UR, et al. Assessment of left ventricular function in patients with ischemic heart disease and heart failure by three-dimensional echocardiography and cardiac magnetic resonance imaging(abstr) J Am Coll Cardiol 2006;47(Suppl A):147A. 16. Suffoletto MS, Dohi K, Tanabe M, et al. Dyssynchrony in heart failure patients with narrow QRS versus wide QRSinsights from radial strain by echocardiographic speckle tracking. (abstr) J Am Coll Cardiol 2006;47(Suppl A):134A. 17. Prakash M, Coplan N, Dhingra C, Baweja P, Panagopoulos G. Prognostic significance of systolic blood pressure increase in patients referred for exercise stress testing(abstr) J Am Coll Cardiol 2006;47(Suppl A):154A.
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Cardiovascular magnetic...
Computed tomography