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Background: Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow-up and provide incremental value over the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations in predicting atherosclerotic cardiovascular disease events., Methods: A total of 10 470 men and women without prior atherosclerotic cardiovascular disease events or heart failure in the ARIC Study (Atherosclerosis Risk in Communities) underwent retinal photography at visit 3 (1993-1995)., Results: During a mean follow-up of 16 years, there were 1779 incident coronary heart disease events, 548 ischemic strokes, 1395 heart failure events, and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08-1.18; HR, 1.18; 95% CI, 1.07-1.31; and HR, 1.10; 95% CI, 1.00-1.20 per 1-SD increase) and narrower retinal arterioles (HR, 1.06; 95% CI, 1.01-1.11; HR, 1.14; 95% CI, 1.03-1.26; and HR, 1.13; 95% CI, 1.03-1.24 per 1-SD decrease) had a higher risk of death and stroke in both sexes and incident coronary heart disease in women but not men (interaction P=0.02) after adjustment for the Pooled Cohort Equations risk score variables. The association between retinal vessel caliber and heart failure was nonsignificant after adjustment for systolic blood pressure. Among women with Pooled Cohort Equations-predicted 10-year atherosclerotic cardiovascular disease event risk <5% (overall risk, 3.9%), women in the narrowest arteriolar quartile had a 10-year event rate of 5.6% compared with 2.8% for women in the widest quartile (5.0% versus 3.4% for wider versus narrower venules). Retinal vessel caliber reclassified 21% of low-risk women (11% of all women) as intermediate risk (>5%)., Conclusions: Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both sexes and coronary heart disease in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in atherosclerotic cardiovascular disease event risk prediction in low-risk women., (© 2016 American Heart Association, Inc.)

Background: The most appropriate score for evaluating the pretest probability of obstructive coronary artery disease (CAD) is unknown. We sought to compare the Diamond-Forrester (DF) score with the 2 CAD consortium scores recently recommended by the European Society of Cardiology., Methods: We included 2274 consecutive patients (age, 56±13 years; 57% male) without prior CAD referred for coronary computed tomographic angiography. Computed tomographic angiography findings were used to determine the presence or absence of obstructive CAD (≥50% stenosis). We compared the DF score with the 2 CAD consortium scores with respect to their ability to predict obstructive CAD and the potential implications of these scores on the downstream use of testing for CAD, as recommended by current guidelines., Results: The DF score did not satisfactorily fit the data and resulted in a significant overestimation of the prevalence of obstructive CAD (P<0.001); the CAD consortium basic score had no significant lack of fitness; and the CAD consortium clinical provided adequate goodness of fit (P=0.39). The DF score had a lower discrimination for obstructive CAD, with an area under the receiver-operating characteristics curve of 0.713 versus 0.752 and 0.791 for the CAD consortium models (P<0.001 for both). Consequently, the use of the DF score was associated with fewer individuals being categorized as requiring no additional testing (8.3%) compared with the CAD consortium models (24.6% and 30.0%; P<0.001). The proportion of individuals with a high pretest probability was 18% with the DF and only 1.1% with the CAD consortium scores (P<0.001) CONCLUSIONS: Among contemporary patients referred for noninvasive testing, the DF risk score overestimates the risk of obstructive CAD. On the other hand, the CAD consortium scores offered improved goodness of fit and discrimination; thus, their use could decrease the need for noninvasive or invasive testing while increasing the yield of such tests., (© 2016 American Heart Association, Inc.)

Objectives: Our purpose was to evaluate the long-term benefit of myocardial viability assessment for stratifying risk and selecting patients with low ejection fraction for coronary artery bypass grafting and to determine the relation between the severity of anginal symptoms, the amount of ischemic myocardium, and clinical outcome., Methods: We studied 93 consecutive patients with severe coronary artery disease and low ejection fraction (median, 25%) who underwent positron emission tomography to delineate the extent of perfusion-metabolism mismatch (reflecting hibernating myocardium) for potential myocardial revascularization. Median follow-up was 4 years (range, 0 to 6.2 years)., Results: Fifty patients received medical therapy, and 43 patients underwent bypass grafting. In Cox survival models, heart failure class, prior myocardial infarction, and positron emission tomographic mismatch were the best predictors of survival. Patients with positron emission tomographic mismatch receiving bypass grafting had improved 4-year survival compared with those on medical therapy (75% versus 30%; P =.007) and a significant improvement in angina and heart failure symptoms. In patients without positron emission tomographic mismatch, bypass grafting tended to improve survival and symptoms only in those patients with severe angina (100% versus 60%; P =.085), whereas no survival advantage was apparent in patients with minimal or no anginal symptoms (63% versus 52%; P =.462)., Conclusions: Patients with low ejection fraction and evidence of viable myocardium by positron emission tomography have improved survival and symptoms with coronary bypass grafting compared with medical therapy. In patients without evidence of viability, survival and symptom improvement with bypass grafting are apparent only among those patients with severe angina.

Background: Studies of patients with coronary artery disease and left ventricular dysfunction have shown that preoperative quantification of myocardial viability may be clinically useful to identify those patients who will benefit most from revascularization both functionally and prognostically. However, the relation between preoperative extent of viability and change in heart failure symptoms has not been documented carefully. We assessed the relation between the magnitude of improvement in heart failure symptoms after coronary artery bypass surgery (CABG) and the extent of myocardial viability as assessed by use of quantitative analysis of preoperative positron emission tomography (PET) images., Methods and Results: We studied 36 patients with ischemic cardiomyopathy (mean left ventricular ejection fraction, 28 +/- 6%) undergoing CABG. Preoperative extent and severity of perfusion abnormalities and myocardial viability (flow-metabolism mismatch) were assessed by use of quantitative analysis of PET images with 13N ammonia and fluorine-18-deoxyglucose. Each patient's functional status was determined before and after CABG by use of a Specific Activity Scale. Mean perfusion defect size and severity were 63 +/- 13% and 33 +/- 12%, respectively. Total extent of a PET mismatch correlated linearly and significantly with percent improvement in functional status after CABG (r = .87, P < .0001). A blood flow-metabolism mismatch > or = 18% was associated with a sensitivity of 76% and a specificity of 78% for predicting a change in functional status after revascularization. Patients with large mismatches (> or = 18%) achieved a significantly higher functional status compared with those with minimal or no PET mismatch (< 5%) (5.7 +/- 0.8 versus 4.9 +/- 0.7 metabolic equivalents, P = .009). This resulted in an improvement of 107% in patients with large mismatches compared with only 34% in patients with minimal or no PET mismatch., Conclusions: In patients with ischemic cardiomyopathy, the magnitude of improvement in heart failure symptoms after CABG is related to the preoperative extent and magnitude of myocardial viability as assessed by use of PET imaging. Patients with large perfusion-metabolism mismatches exhibit the greatest clinical benefit after CABG.

Background: Coronary arteriography is considered the "gold standard" for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography., Methods and Results: We studied 28 subjects: 18 patients with coronary artery disease (66 +/- 8 years) and 10 age-matched healthy volunteers (64 +/- 13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non-infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4 +/- 0.4 versus 2.6 +/- 0.7, respectively; P = NS). Quantitative PET estimates of hyperemic blood flow (r = .81, P < .00001), flow reserve (r = .78, P < .00001), and an index of the "minimal coronary resistance" (r = .78, P < .00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4 +/- 0.4 versus 1.8 +/- 0.5, respectively; P = .04)., Conclusions: In patients with coronary artery disease, non-invasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.

The reported mortality of patients with coronary artery disease (CAD) and congestive heart failure is high but variable. In the clinical management of these patients, the available treatment choices are medical therapy, cardiac transplantation and myocardial revascularization. Myocardial revascularization has become an attractive alternative in the management of patients with CAD and poor left ventricular function because medical therapy is associated with a high mortality and cardiac transplantation is expensive and not practical due to shortage of donor hearts. Myocardial revascularization, however, should be recommended in those patients in whom the procedure is very likely to reverse regional and global left ventricular dysfunction and to improve heart failure symptoms and survival. Thallium-201 rest-redistribution myocardial scintigraphy and PET imaging of myocardial perfusion and 18F-fluoro-deoxyglucose metabolism have been extensively evaluated for the assessment of myocardial viability and for prediction of recovery of regional left ventricular dysfunction following myocardial revascularization; with positive and negative predictive accuracies of 72% and 70% for 201Tl rest-redistribution imaging and 83% and 84% for perfusion-metabolism PET imaging. Both modalities also are predictive of improvement in left ventricular ejection fraction after myocardial revascularization. Patients with congestive heart failure who demonstrate the PET pattern of mismatch are more likely to improve their heart failure symptoms following revascularization than those without the mismatch pattern. Furthermore, the PET pattern of mismatch identifies a subgroup of patients who are at very high risk for cardiac death on medical therapy. Survival of these patients can be significantly improved by myocardial revascularization.

Objectives: This study aimed to determine whether angiographically visualized collateral vessels in patients with chronic coronary artery disease imply the presence of viable myocardium in asynergic regions subtended by completely occluded coronary arteries., Background: Patients with chronic coronary artery disease who are being considered for revascularization frequently exhibit angiographically visualized collateral vessels to completely occluded coronary arteries supplying severely asynergic myocardial regions. However, little is known about the relation between angiographic collateral flow and myocardial viability in these patients., Methods: We studied 42 patients with 78 completely occluded coronary arteries supplying asynergic territories. Angiographic collateral vessels were interpreted as absent (grade 1) in 14 patients, minimal (grade 2) in 27 and well developed (grade 3) in 37. Myocardial viability was determined with positron emission tomography using nitrogen-13 (N-13) ammonia and fluorine-18 (F-18) deoxyglucose for assessment of regional perfusion and glucose uptake, respectively. Positron emission tomographic patterns were interpreted as mismatch (perfusion defect with enhanced F-18 deoxyglucose uptake); transmural match (severe concordant reduction or absence of both perfusion and F-18 deoxyglucose uptake) or nontransmural match (mild to moderate concordant reduction of both perfusion and F-18 deoxyglucose uptake)., Results: There was no significant correlation (p = 0.14) between the severity of perfusion deficit assessed by positron emission tomography and the collateral grade. The extent of mismatch was unrelated to either the presence or the magnitude of collateral vessels. Conversely, with increasing collateral vessels from grade 1 to 3, the total extent of positron emission tomographic match remained similar, whereas the ratio of transmural to nontransmural match decreased. Myocardial viability was usually present in severely hypokinetic regions (82%). It was lower in akinetic-dyskinetic regions (49%). Of the 64 regions with angiographic collateral vessels, 37 (58%) (95% confidence interval [CI] 46% to 70%) showed positron emission tomographic mismatch. In contrast, 7 (50%) of 14 (95% CI 24% to 76%) regions without collateral vessels on angiography exhibited positron emission tomographic mismatch. The presence of angiographically visualized collateral vessels was a sensitive (84%) but not specific (21%) marker of viability., Conclusions: In patients with chronic coronary artery disease, angiographically visualized collateral vessels to asynergic myocardial regions subtended by occluded coronary arteries do not always imply the presence of viable myocardium, suggesting that revascularization may not always provide a functional benefit.

Patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction have a high but variable annual mortality and some may benefit from myocardial revascularization. This study aimed to evaluate the prognostic value of positron emission tomography (PET), and its interrelation with the choice of medical therapy or revascularization for predicting survival and improvement in symptoms of heart failure in patients with CAD and LV dysfunction. Ninety-three consecutive patients with angiographic CAD and a mean LV ejection fraction of 0.25 who underwent cardiac PET studies for assessment of hypoperfused yet viable myocardium ("mismatch pattern") using N-13 ammonia and 18-F deoxyglucose were followed up for an average of 13.6 months. Fifty patients underwent medical treatment and 43 underwent revascularization. The Cox model analysis showed that the extent of mismatch had a negative effect (p = 0.02), whereas revascularization had a positive effect on survival (p = 0.04). The annual survival probability of patients with mismatch receiving medical therapy was lower than of those without mismatch (50 vs 92%, p = 0.007). Patients with mismatch who underwent revascularization had a higher survival rate than those treated medically (88 vs 50%, P = 0.03). The presence of mismatch also predicted improvement in heart failure symptoms after revascularization (p < 0.001). These results suggest that the presence of mismatch in patients with CAD and severe LV dysfunction is associated with poor annual survival with medical therapy. Revascularization in patients with PET mismatch appears to be associated with improved survival and heart failure symptoms.