J Am Coll Cardiol. 2010; 56(1):983-991

Shingo Kato, Kakuya Kitagawa, Nanaka Ishida, Masaki Ishida, Motonori Nagata, Yasutaka Ichikawa, Kazuhiro Katahira, Yuji Matsumoto, Koji Seo, Reiji Ochiai, Yasuyuki Kobayashi, Hajime Sakuma

OBJECTIVES: This national multicenter study determined the diagnostic performance of 1.5-T whole-heart coronary magnetic resonance angiography (MRA) in patients with suspected coronary artery disease (CAD). Whole-heart coronary MRA using steady-state free precession allows noninvasive detection of CAD without the administration of contrast medium. However, the accuracy of this approach has not been determined in a multicenter trial.

METHODS: Using a 1.5-T magnetic resonance imaging unit, free-breathing steady-state free precession whole-heart coronary MRA images were acquired for 138 patients with suspected CAD at 7 hospitals. The accuracy of MRA for detecting a ≥50% reduction in diameter was determined using X-ray coronary angiography as the reference method.

RESULTS: Acquisition of whole-heart coronary MRA images was performed in 127 (92%) of 138 patients with an average imaging time of 9.5 ± 3.5 min. The areas under the receiver-operator characteristic curve from MRA images according to vessel- and patient-based analyses were 0.91 (95% confidence interval [CI]: 0.87 to 0.95) and 0.87 (95% CI: 0.81 to 0.93), respectively. The sensitivity, specificity, positive and negative predictive values, and accuracy of MRA according to a patient-based analysis were 88% (49 of 56, 95% CI: 75% to 94%), 72% (51 of 71, 95% CI: 60% to 82%), 71% (49 of 69, 95% CI: 59% to 81%), 88% (51 of 58, 95% CI: 76% to 95%), and 79% (100 of 127, 95% CI: 72% to 86%), respectively.

CONCLUSIONS: Non–contrast-enhanced whole-heart coronary MRA at 1.5-T can noninvasively detect significant CAD with high sensitivity and moderate specificity. A negative predictive value of 88% indicates that whole-heart coronary MRA can rule out CAD.

PMID:

Circ Arrhythm Electrophysiol. 2010; 3(4):345-350

Thanassoulis G, Massaro JM, O'Donnell CJ, Hoffmann U, Levy D, Ellinor PT, Wang TJ, Schnabel RB, Vasan RS, Fox CS, Benjamin EJ

OBJECTIVES: Obesity represents an important risk factor for atrial fibrillation (AF). We tested the hypothesis that pericardial fat, a unique fat deposit in close anatomic proximity to cardiac structures and autonomic fibers, is associated with prevalent AF.

METHODS: Participants from the Framingham Heart Study underwent multidetector computed tomography from 2002 to 2005. We estimated the association between quantitative pericardial, intrathoracic and visceral adipose tissue volumes (per standard deviation of volume) with prevalent AF adjusting for established AF risk factors (age, sex, systolic blood pressure, blood pressure treatment, PR interval, and clinically significant valvular disease).

RESULTS: Of the 3217 eligible participants (mean age, 50.6+/-10.1 years; 48% women), 54 had a confirmed diagnosis of AF. Pericardial fat but not intrathoracic or visceral abdominal fat was associated with prevalent AF in multivariable-adjusted models (odds ratio per standard deviation of pericardial fat volume, 1.28; 95% confidence intervals, 1.03 to 1.58). Further adjustments for body mass index, heart failure, myocardial infarction, and intrathoracic fat volume did not materially change the association between pericardial fat and AF.

CONCLUSIONS: Pericardial fat was associated with prevalent AF even after adjustment for AF risk factors, including body mass index. If this association is replicated, further investigations into the mechanisms linking pericardial fat to AF are merited.

PMID: 20558845

J Am Coll Cardiol. 2010; 56(7):206-214

Jonathan P. Piccini, Aijing Z. Starr, John R. Horton, Linda K. Shaw, Kerry L. Lee, Sana M. Al-Khatib, Ami E. Iskandrian, Christopher M. O'Connor, and Salvador Borges-Neto

OBJECTIVES: The aim of this study was to determine whether single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is an effective method of risk stratification for sudden cardiac death (SCD) in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) >35%. Most victims of SCD have an LVEF >35%.

METHODS: The study population included 4,865 patients with CAD and LVEF >35% who underwent gated SPECT MPI. We used Cox proportional hazard modeling to examine the relationship between patient characteristics and SCD.

RESULTS: The median age of the population was 63 years (25th, 75th percentile: 54, 71 years), and the median LVEF was 56% (25th, 75th percentile: 50%, 64%). The median follow-up for all patients was 6.5 years (25th, 75th percentile: 3.6, 9.3 years). During follow-up, there were 161 SCDs (3.3%). After multivariable adjustment, LVEF, the Charlson index, hypertension, smoking, antiarrhythmic drug therapy, and the summed stress score (SSS) were associated with SCD (all p < 0.05). For each 3-U increase in the SSS, the hazard ratio for SCD was 1.13 (95% confidence interval: 1.04 to 1.23). The addition of perfusion data to the clinical history and LVEF was associated with increased discrimination for SCD events (c-index 0.728). Risk stratification with a derived SPECT nomogram did not result in statistically significant net reclassification improvement (p = 0.26) or integrated discrimination improvement (p = 0.38).

CONCLUSIONS: Among patients with CAD and LVEF >35%, the extent of stress MPI perfusion defects is associated with an increased risk of SCD. Future large prospective studies should address the role of perfusion imaging in the identification of high-risk patients with LVEF >35% who might benefit from ICD implantation.

PMID: 19808541

J Cardiovasc Magn Reson.. 2010; 12(1):29

Hamon M, Fau G, Née G, Ehtisham J, Morello R, Hamon M

OBJECTIVES: Evaluation of the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance for the diagnosis of significant obstructive coronary artery disease (CAD) through meta-analysis of the available data.

METHODS: Original articles in any language published before July 2009 were selected from available databases (MEDLINE, Cochrane Library and BioMedCentral) using the combined search terms of magnetic resonance, perfusion, and coronary angiography; with the exploded term coronary artery disease. Statistical analysis was only performed on studies that: (1) used a [greater than or equal to] 1.5 Tesla MR scanner; (2) employed invasive coronary angiography as the reference standard for diagnosing significant obstructive CAD, defined as a [greater than or equal to] 50% diameter stenosis; and (3) provided sufficient data to permit analysis.

RESULTS: From the 263 citations identified, 55 relevant original articles were selected. Only 35 fulfilled all of the inclusion criteria, and of these 26 presented data on patient-based analysis. The overall patient-based analysis demonstrated a sensitivity of 89% (95% CI: 88-91%), and a specificity of 80% (95% CI: 78-83%). Adenosine stress perfusion CMR had better sensitivity than with dipyridamole (90% (88-92%) versus 86% (80-90%), P = 0.022), and a tendency to a better specificity (81% (78-84%) versus 77% (71-82%), P = 0.065).

CONCLUSIONS: Stress perfusion CMR is highly sensitive for detection of CAD but its specificity remains moderate.

PMID: 20482819

Circulation: Cardiovascular Imaging. 2010; 3(4):120-123

Thanassoulis G, Massaro JM, Hoffmann U, Mahabadi A, Vasan RS, O'Donnell CJ, Fox CS

OBJECTIVES: Pericardial and intra-thoracic fat depots may represent novel risk factors for obesity-related cardiovascular disease. We sought to determine the prevalence, distribution and risk factor correlates of high pericardial and intra-thoracic fat deposits.

METHODS: Participants from the Framingham Heart Study (n=3312; mean age 52 years, 48% women) underwent multi-detector CT imaging in 2002-2005; high pericardial and high intra-thoracic fat were defined based on the sex-specific 90th percentile for these fat depots in a healthy reference sample.

RESULTS: For men and women, the prevalence of high pericardial fat was 29.3% and 26.3%, respectively, and high intra-thoracic fat was 31.4% and 35.3%, respectively. Overall, 22.1% of the sample was discordant for pericardial and intra-thoracic fat depots: 8.3% had high pericardial but normal intra-thoracic fat, and 13.8% had high intra-thoracic but normal pericardial fat. Higher body mass index, higher waist circumference (WC) and increased prevalence of metabolic syndrome were more likely in participants with high intra-thoracic fat depots than with high pericardial fat (p<0.05 for all comparisons). High abdominal visceral adipose tissue was more frequent in participants with high intra-thoracic adipose tissue compared to those with high pericardial fat (p<0.001). Intra-thoracic fat, but not WC, was more highly correlated with VAT (r=0.76 and 0.78 in men and women, respectively; p<0.0001) than with SAT (r=0.46 and 0.54 in men and women, respectively; p<0.0001).

CONCLUSIONS: Although prevalence of pericardial fat and intra-thoracic fat were comparable at 30%, intra-thoracic fat correlated more closely with metabolic risk and visceral fat. Intra-thoracic fat may be a potential marker of metabolic risk and visceral fat on thoracic imaging.

PMID: 20525769

Journal of Cardiovascular Magnetic Resonance. 2010; 12(30):543-551

Fluechter S, Kuschyk J, Wolpert C, Doesch C, Veltmann C, Haghi D, Schoenberg SO, Sueselbeck T, Germans T, Borggrefe M, Streitner F, Papavassiliu T

OBJECTIVES: Myocardial fibrosis is frequently identified in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to investigate the role of myocardial fibrosis detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) as a potential arrhythmogenic substrate in HCM. We hypothesized that the extent of LGE might be associated with the inducibility of ventricular tachyarrhythmias (VT) during programmed ventricular stimulation (PVS).

METHODS: We evaluated retrospectively LGE CMR of 76 consecutive HCM patients, of which 43 presented with one or more risk factors for sudden cardiac death (SCD) and were therefore clinically classified as high-risk patients. Of these 43 patients, 38 additionally underwent an electrophysiological testing (EP). CMR indices and the extent of LGE, given as the % of LV mass with LGE were correlated with the presence of risk factors for SCD and the results of EP.

RESULTS: High-risk patients had a significant higher prevalence of LGE than low-risk patients (29/43 [67%] versus 14/33 [47%]; p=0.03). Also the % of LV mass with LGE was significantly higher in high-risk patients than in low-risk patients (14% versus 3%, p=0.001, respectively). Of the 38 high- risk patients, 12 had inducible VT during EP. LV function, volumes and mass were comparable in patients with and without inducible VT. However, the % of LV mass with LGE was significantly higher in patients with inducible VT compared to those without (22% versus 10 %, p=0.03). The prevalence of LGE was, however, comparable between HCM patients with and those without inducible VT (10/12 [83%] versus 15/26 [58%]; p=0.12). In the univariate analysis the % of LV mass with LGE and the septal wall thickness were significantly associated with the high-risk group (p= 0.001 and 0.004, respectively). Multivariate analysis demonstrated that the extent of LGE was the only independent predictor of the risk group (p=0.03).

CONCLUSIONS: The extent of LGE in HCM patients correlated with risk factors of SCD and the likelihood of inducible VT. Furthermore, LGE extent was the only independent predictor of the risk group. This supports the hypothesis that the extent of fibrosis may serve as potential arrhythmogenic substrate for the occurrence of VT, especially in patients with clinical risk factors for SCD.

PMID: 20492668

JAMA. 2010; 303(16):1610-1616

Polonsky TS, McClelland RL, Jorgensen NW, Bild DE, Burke GL, Guerci AD, Greenland P

OBJECTIVES: : The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear. To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk.

METHODS: CACS was measured by computed tomography in 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded from the primary analysis. Five-year risk estimates for incident CHD were categorized as 0% to less than 3%, 3% to less than 10%, and 10% or more using Cox proportional hazards models. Model 1 used age, sex, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement and compared the distribution of risk using model 2 vs model 1.

RESULTS: During a median of 5.8 years of follow-up among a final cohort of 5878, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% confidence interval, 0.16-0.34; P < .001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2.

CONCLUSIONS: In this multi-ethnic cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.

PMID: 20424251

AJR. 2010; 194(5):1235-1243

Johnson KM, Dowe DA

OBJECTIVE: The Framingham risk score is often recommended as the starting point for coronary disease screening. We compared the sensitivity of the Framingham risk score for moderate or greater degrees of atherosclerosis to the sensitivity achieved by simple observation of whether any coronary calcium is present. The reference standard was plaque burden as determined by coronary CT angiography.

METHODS: Of 1,416 men (mean age, 51.4 +/- 9.9 [SD] years) and 707 women (56.9 +/- 10.6 years), most were asymptomatic. Plaque burden (segment plaque score) and stenoses burden (Duke prognostic score) were estimated. A segment plaque score > 4 or a Duke prognostic score >3 indicated moderate or greater disease burden.

RESULTS: For a segment plaque score > 4, the presence of any calcium was 98% sensitive in men and 97% sensitive in women, whereas a Framingham risk score >10% was 74% sensitive in men and 36% sensitive in women. The negative likelihood ratio for the presence of calcium was 0.04 in subjects of either sex, whereas, for a Framingham risk score >3, calcium was 97% sensitive in men and 92% sensitive in women, whereas a Framingham risk score >10% was 88% sensitive in men and 35% sensitive in women. The negative likelihood ratio of calcium presence was 0.05 in men and 0.13 in women, whereas the negative likelihood ratio for a Framingham risk score

CONCLUSIONS: If subjects are excluded from further screening because they are in the Framingham low-risk category, almost two thirds of women and a quarter of men with substantial atherosclerosis will be missed. In contrast, the simple observation of any coronary calcium is highly sensitive and moderately specific.

PMID: 20410409

JACC Cardiovasc Imaging. 2010; 3(4):352-360

Cheng VY, Dey D, Tamarappoo B, Nakazato R, Gransar H, Miranda-Peats R, Ramesh A, Wong ND, Shaw LJ, Slomka PJ, Berman DS

OBJECTIVES: We aimed to evaluate whether pericardial fat has value in predicting the risk of future adverse cardiovascular outcomes. Pericardial fat volume (PFV) and thoracic fat volume (TFV) can be routinely measured from noncontrast computed tomography (NCT) performed for calculating coronary calcium score (CCS) and may predict major adverse cardiac event (MACE) risk.

METHODS: From a registry of 2,751 asymptomatic patients without known cardiac artery disease and 4-year follow-up for MACE (cardiac death, myocardial infarction, stroke, late revascularization) after NCT, we compared 58 patients with MACE with 174 same-sex, event-free control subjects matched by a propensity score to account for age, risk factors, and CCS. The TFV was automatically calculated, and PFV was calculated with manual assistance in defining the pericardial contour, within which fat voxels were automatically identified. Independent relationships of PFV and TFV to MACE were evaluated using conditional multivariable logistic regression.

RESULTS: Patients experiencing MACE had higher mean PFV (101.8 +/- 49.2 cm(3) vs. 84.9 +/- 37.7 cm(3), p = 0.007) and TFV (204.7 +/- 90.3 cm(3) vs. 177 +/- 80.3 cm(3), p = 0.029) and higher frequencies of PFV >125 cm(3) (33% vs. 14%, p = 0.002) and TFV >250 cm(3) (31% vs. 17%, p = 0.025). After adjustment for Framingham risk score (FRS), CCS, and body mass index, PFV and TFV were significantly associated with MACE (odds ratio [OR]: 1.74, 95% confidence interval [CI]: 1.03 to 2.95 for each doubling of PFV; OR: 1.78, 95% CI: 1.01 to 3.14 for TFV). The area under the curve from receiver-operator characteristic analyses showed a trend of improved MACE prediction when PFV was added to FRS and CCS (0.73 vs. 0.68, p = 0.058). Addition of PFV, but not TFV, to FRS and CCS improved estimated specificity (0.72 vs. 0.66, p = 0.008) and overall accuracy (0.70 vs. 0.65, p = 0.009) in predicting MACE.

CONCLUSIONS: Asymptomatic patients who experience MACE exhibit greater PFV on pre-MACE NCT when they are compared with event-free control subjects with similar cardiovascular risk profiles. Our preliminary findings suggest that PFV may help improve prediction of MACE.

PMID: 20394896

J Am Coll Cardiol. 2010; 55(16):1649-1660

Sebastiaan C.A.M. Bekkers, Saami K. Yazdani, Renu Virmani, and Johannes Waltenberger

Successful restoration of epicardial coronary artery patency after prolonged occlusion might result in microvascular obstruction (MVO) and is observed both experimentally as well as clinically. In reperfused myocardium, myocytes appear edematous and swollen from osmotic overload. Endothelial cell changes usually accompany the alterations seen in myocytes but lag behind myocardial cell injury. Endothelial cells become voluminous, with large intraluminal endothelial protrusions into the vascular lumen, and together with swollen surrounding myocytes occlude capillaries. The infiltration and activation of neutrophils and platelets and the deposition of fibrin also play an important role in reperfusion-induced microvascular damage and obstruction. In addition to these ischemia-reperfusion-related events, coronary microembolization of atherosclerotic debris after percutaneous coronary intervention is responsible for a substantial part of clinically observed MVO. Microvascular flow after reperfusion is spatially and temporally complex. Regions of hyperemia, impaired vasodilatory flow reserve and very low flow coexist and these perfusion patterns vary over time as a result of reperfusion injury. The MVO first appears centrally in the infarct core extending toward the epicardium over time. Accurate detection of MVO is crucial, because it is independently associated with adverse ventricular remodeling and patient prognosis. Several techniques (coronary angiography, myocardial contrast echocardiography, cardiovascular magnetic resonance imaging, electrocardiography) measuring slightly different biological and functional parameters are used clinically and experimentally. Currently there is no consensus as to how and when MVO should be evaluated after acute myocardial infarction.

PMID: