Objectives In this study, we systematically assessed the diagnostic and prognostic value of absence of coronary artery calcification (CAC) in asymptomatic and symptomatic individuals. Background ...Presence of CAC is a well-established marker of coronary plaque burden and is associated with a higher risk of adverse cardiovascular outcomes. Absence of CAC has been suggested to be associated with a very low risk of significant coronary artery disease, as well as minimal risk of future events. Methods We searched online databases (e.g., PubMed and MEDLINE) for original research articles published in English between January 1990 and March 2008 examining the diagnostic and prognostic utility of CAC. Results A systematic review of published articles revealed 49 studies that fulfilled our criteria for inclusion. These included 13 studies assessing the relationship of CAC with adverse cardiovascular outcomes in 64,873 asymptomatic patients. In this cohort, 146 of 25,903 patients without CAC (0.56%) had a cardiovascular event during a mean follow-up period of 51 months. In the 7 studies assessing the prognostic value of CAC in a symptomatic population, 1.80% of patients without CAC had a cardiovascular event. Overall, 18 studies demonstrated that the presence of any CAC had a pooled sensitivity and negative predictive value of 98% and 93%, respectively, for detection of significant coronary artery disease on invasive coronary angiography. In 4,870 individuals undergoing myocardial perfusion and CAC testing, in the absence of CAC, only 6% demonstrated any sign of ischemia. Finally, 3 studies demonstrated that absence of CAC had a negative predictive value of 99% for ruling out acute coronary syndrome. Conclusions On the basis of our review of more than 85,000 patients, we conclude that the absence of CAC is associated with a very low risk of future cardiovascular events, with modest incremental value of other diagnostic tests in this very low-risk group.
Objectives This study sought to determine the feasibility of performing a comprehensive cardiac computed tomographic (CT) examination incorporating stress and rest myocardial perfusion imaging ...together with coronary computed tomography angiography (CTA). Background Although cardiac CT can identify coronary stenosis, very little data exist on the ability to detect stress-induced myocardial perfusion defects in humans. Methods Thirty-four patients who had a nuclear stress test and invasive angiography were included in the study. Dual-source computed tomography (DSCT) was performed as follows: 1) stress CT: contrast-enhanced scan during adenosine infusion; 2) rest CT: contrast-enhanced scan using prospective triggering; and 3) delayed scan: acquired 7 min after rest CT. Images for CTA, computed tomography perfusion (CTP), and single-photon emission computed tomography (SPECT) were each read by 2 independent blinded readers. Results The DSCT protocol was successfully completed for 33 of 34 subjects (average age 61.4 ± 10.7 years; 82% male; body mass index 30.4 ± 5 kg/m2 ) with an average radiation dose of 12.7 mSv. On a per-vessel basis, CTP alone had a sensitivity of 79% and a specificity of 80% for the detection of stenosis ≥50%, whereas SPECT myocardial perfusion imaging had a sensitivity of 67% and a specificity of 83%. For the detection of vessels with ≥50% stenosis with a corresponding SPECT perfusion abnormality, CTP had a sensitivity of 93% and a specificity of 74%. The CTA during adenosine infusion had a per-vessel sensitivity of 96%, specificity of 73%, and negative predictive value of 98% for the detection of stenosis ≥70%. Conclusions Adenosine stress CT can identify stress-induced myocardial perfusion defects with diagnostic accuracy comparable to SPECT, with similar radiation dose and with the advantage of providing information on coronary stenosis.
Objectives This study sought to determine whether arterial inflammation measured by18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET) improves prediction of cardiovascular disease ...(CVD) beyond traditional risk factors. Background It is unknown whether arterial18 F-FDG uptake measured with routine PET imaging provides incremental value for predicting CVD events beyond Framingham risk score (FRS). Methods We consecutively identified 513 individuals from 6,088 patients who underwent18 F-FDG-PET and computed tomography (CT) imaging at Massachusetts General Hospital between 2005 and 2008 and who met additional inclusion criteria: ≥30 years of age, no prior CVD, and free of cancer. CVD events were independently adjudicated, while blinded to clinical data, using medical records to determine incident stroke, transient ischemic attack, acute coronary syndrome, revascularization, new-onset angina, peripheral arterial disease, heart failure, or CVD death. FDG uptake was measured in the ascending aorta (as target-to-background-ratio TBR), while blinded to clinical data. Results During follow-up (median 4.2 years), 44 participants developed CVD (2 per 100 person-years at risk). TBR strongly predicted subsequent CVD independent of traditional risk factors (hazard ratio: 4.71; 95% confidence interval CI: 1.98 to 11.2; p < 0.001) and (hazard ratio: 4.13; 95% CI: 1.59 to 10.76; p = 0.004) after further adjustment for coronary calcium score. Addition of arterial PET measurement to FRS scores improved the C-statistic (mean ± standard error 0.62 ± 0.03 vs. 0.66 ± 0.03). Further, incorporation of TBR into a model with FRS variables resulted in an integrated discrimination of 5% (95% CI: 0.36 to 9.87). Net reclassification improvements were 27.48% (95% CI: 16.27 to 39.92) and 22.3% (95% CI: 11.54 to 35.42) for the 10% and 6% intermediate-risk cut points, respectively. Moreover, TBR was inversely associated with the timing of CVD (beta −0.096; p < 0.0001). Conclusions Arterial FDG uptake, measured from routinely obtained PET/CT images, substantially improved incident CVD prediction beyond FRS among individuals undergoing cancer surveillance and provided information on the potential timing of such events.
Objective The role of thoracic endovascular aortic repair (TEVAR) in the management of acute type B aortic dissection remains undefined. Entry tear coverage during the acute phase is an appealing ...method to treat acute complications, and by inducing false lumen thrombosis, might also prevent late aneurysm formation. This study evaluated structural changes by serial computed tomography (CT) in the thoracic aorta after TEVAR performed for acute complicated aortic dissection. Methods Between August 2005 and October 2007, 33 patients with complicated acute type B aortic dissection were treated with TEVAR (19 from a prospective industry sponsored trial, 14 from our institution). CT images obtained preprocedurally (PP), at 1 month (1M), and 1 year (1Y) were evaluated for each patient. Four patients with no postprocedural imaging were excluded. The largest diameters of the thoracic aorta, dissection true lumen, and false lumen were recorded at each time point. Canges in total aortic and true and false lumen diameters were evaluated using a mixed effect analysis of variance model of repeated measures. Results The average age was 58 years (range, 38-87 years); 26 (81%) were male. Indications for TEVAR included malperfusion syndrome in 17 (53%), refractory hypertension in 14 (44%), impending rupture in 12 (28%), and refractory pain in 14 (44%); 19 (59%) had more than one indication. The average length of aorta covered was 19.5 cm (range, 10-29.3 cm). The maximum aortic diameter decreased over time ( P = .04) and averaged 39.9 (PP), 41.3 (1M), and 34.8 mm (1Y). The true lumen diameter increased over time ( P = .02) and averaged 23.7 (PP), 29.0 (1M), and 31.1 mm (1Y). The false lumen diameter decreased ( P = .046) and averaged 19.5 (PP), 12.1 (1M), and 9.6 mm (1Y). Partial or complete thrombosis of the false lumen along the stented segment of aorta was recorded in 87% (PP), 93% (1M), and 88% (1Y). Conclusions TEVAR of acute complicated aortic dissection appears to promote early aortic remodeling. Nearly 90% of patients maintained at least partial false lumen thrombosis at 1 year. Because continued false lumen patency correlates strongly with late aneurysm formation, such favorable remodeling is considered a surrogate for prevention of late aneurysm, but longer follow-up is required.
Newer cardiac computed tomographic (CT) technology has permitted comprehensive cardiothoracic evaluations for coronary artery disease, pulmonary embolism, and aortic dissection within a single breath ...hold, independent of the heart rate. We conducted a randomized diagnostic trial to compare the efficiency of a comprehensive cardiothoracic CT examination in the evaluation of patients presenting to the emergency department with undifferentiated acute chest discomfort or dyspnea. We randomized the emergency department patients clinically scheduled to undergo a dedicated CT protocol to assess coronary artery disease, pulmonary embolism, or aortic dissection to either the planned dedicated CT protocol or a comprehensive cardiothoracic CT protocol. All CT examinations were performed using a 64-slice dual source CT scanner. The CT results were immediately communicated to the emergency department providers, who directed further management at their discretion. The subjects were then followed for the remainder of their hospitalization and for 30 days after hospitalization. Overall, 59 patients (mean age 51.2 ± 11.4 years, 72.9% men) were randomized to either dedicated (n = 30) or comprehensive (n = 29) CT scanning. No significant difference was found in the median length of stay (7.6 vs 8.2 hours, p = 0.79), rate of hospital discharge without additional imaging (70% vs 69%, p = 0.99), median interval to exclusion of an acute event (5.2 vs 6.5 hours, p = 0.64), costs of care (p = 0.16), or the number of revisits (p = 0.13) between the dedicated and comprehensive arms, respectively. In addition, radiation exposure (11.3 mSv vs 12.8 mSv, p = 0.16) and the frequency of incidental findings requiring follow-up (24.1% vs 33.3%, p = 0.57) were similar between the 2 arms. Comprehensive cardiothoracic CT scanning was feasible, with a similar diagnostic yield to dedicated protocols. However, it did not reduce the length of stay, rate of subsequent testing, or costs. In conclusion, although this “triple rule out” protocol might be helpful in the evaluation of select patients, these findings suggest that it should not be used routinely with the expectation that it will improve efficiency or reduce resource use.
Summary Background Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the ...effects of mass drug administration in areas with low malaria transmission. Methods We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. Findings The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Interpretation Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing vector control. Unless elimination is achieved, mass drug administration has to be repeated regularly for sustained effect. Funding Bill & Melinda Gates Foundation.
Objective Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably ...detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). Study Design This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). Results MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. Conclusion High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.
We tested the hypothesis that morphologic lesion assessment helps detect acute coronary syndrome (ACS) during index hospitalization in patients with acute chest pain and significant stenosis on ...coronary computed tomographic angiogram (CTA). Patients who presented to an emergency department with chest pain but no objective signs of myocardial ischemia (nondiagnostic electrocardiogram and negative initial biomarkers) underwent CT angiography. CTA was analyzed for degree and length of stenosis, plaque area and volume, remodeling index, CT attenuation of plaque, and spotty calcium in all patients with significant stenosis (>50% in diameter) on CTA. ACS during index hospitalization was determined by a panel of 2 physicians blinded to results of CT angiography. For lesion characteristics associated with ACS, we determined cutpoints optimized for diagnostic accuracy and created lesion scores. For each score, we determined the odds ratio (OR) and discriminatory capacity for the prediction of ACS. Of the overall population of 368 patients, 34 had significant stenosis and 21 of those had ACS. Scores A (remodeling index plus spotty calcium: OR 3.5, 95% confidence interval CI 1.2 to 10.1, area under curve AUC 0.734), B (remodeling index plus spotty calcium plus stenosis length: OR 4.6, 95% CI 1.6 to 13.7, AUC 0.824), and C (remodeling index plus spotty calcium plus stenosis length plus plaque volume <90 HU: OR 3.4, 95% CI 1.5 to 7.9, AUC 0.833) were significantly associated with ACS. In conclusion, in patients presenting with acute chest pain and stenosis on coronary CTA, a CT-based score incorporating morphologic characteristics of coronary lesions had a good discriminatory value for detection of ACS during index hospitalization.
We sought to evaluate the ability of the Diamond and Forrester method (DFM) and the Duke Clinical Score (DCS) to predict obstructive coronary artery disease (CAD) on coronary computed tomographic ...angiography (CCTA) and the effect of these different risk scores on the appropriateness level using the 2010 Appropriate Use Criteria. Consecutive symptomatic patients who underwent CCTA for evaluation of CAD (n = 114) were classified as having a low, intermediate, or high pretest probability using the DFM and DCS. Using the Appropriate Use Criteria, the indications for CCTA were classified according to the pretest probability and previous testing. The CCTA results were classified as revealing obstructive (≥70% stenosis), nonobstructive (<70%), or no CAD. When the patients' risk was classified using the DFM, 18% were low, 65% intermediate, and 17% high risk. When using the DCS, 53% of patients had a reclassification of their risk, most of whom changed from intermediate to either low or high risk (50% low, 19% intermediate, 35% high risk). The net reclassification improvement for the prediction of obstructive CAD was 51% (p = 0.01). Of the 37 patients who were reclassified as low risk, 36 (97%) lacked obstructive CAD. Appropriateness for CCTA was reclassified for 13% of patients when using the DCS instead of the DFM, and the number of appropriate examinations was significantly fewer (68% vs 55%, p <0.001). In conclusion, reclassification of risk using the DCS instead of the DFM resulted in improved prediction of obstructive CAD on CCTA, especially in low-risk patients. More patients were categorized as having a high pretest probability of CAD, resulting in reclassification of their examination indications as uncertain or inappropriate. These results identify the need for improved pretest risk scores for noninvasive tests such as CCTA and suggest that the method of risk assessment could have important implications for patient selection and quality assurance programs.
BACKGROUND Mechanisms of decreased exercise capacity in patients with hypertrophic cardiomyopathy (HCM) are not well understood. Sleep-disordered breathing (SDB) is a highly prevalent but treatable ...disorder in patients with HCM. The role of comorbid SDB in the attenuated exercise capacity in HCM has not been studied previously. METHODS Overnight oximetry, cardiopulmonary exercise testing, and echocardiographic studies were performed in consecutive patients with HCM seen at the Mayo Clinic. SDB was considered present if the oxygen desaturation index (number of ≥ 4' desaturations/h) was ≥ 10. Peak oxygen consumption ( V. o2 peak) (the most reproducible and prognostic measure of cardiovascular fitness) was then correlated with the presence and severity of SDB. RESULTS A total of 198 patients with HCM were studied (age, 53 ± 16 years; 122 men), of whom 32' met the criteria for the SDB diagnosis. Patients with SDB had decreased V. o2 peak compared with those without SDB (16 mL O2 /kg/min vs 21 mL O2 /kg/min, P < .001). SDB remained significantly associated with V. o2 peak after accounting for confounding clinical variables ( P < .001) including age, sex, BMI, atrial fibrillation, and coronary artery disease. CONCLUSIONS In patients with HCM, the presence of SDB is associated with decreased V. o2 peak. SDB may represent an important and potentially modifiable contributor to impaired exercise tolerance in this unique population.
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