Pasquale Perrone-Filardi

Concordance and discordance between stress-redistribution-reinjection and rest-redistribution thallium imaging for assessing viable myocardium. Comparison with metabolic activity by positron emission tomography.

BACKGROUNDnStress thallium scintigraphy provides important diagnostic and prognostic information in patients with coronary artery disease by demonstrating regional myocardial ischemia. However, if the clinical question being addressed is whether a region is viable and not whether there is inducible ischemia, then it may be more reasonable to perform rest-redistribution imaging rather than stress-redistribution imaging followed by either reinjection or late redistribution. Therefore, we determined whether stress-redistribution-reinjection and rest-redistribution imaging provide the same information regarding myocardial viability.nnnMETHODS AND RESULTSnBoth stress-redistribution-reinjection and rest-redistribution thallium single photon emission computed tomographic imaging was performed in 41 patients with chronic stable coronary artery disease, with quantitative analysis of regional thallium activity. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution images were completed. Of the 155 myocardial regions with perfusion defects on the stress images, 91 (59%) were irreversible on conventional 3- to 4-hour redistribution images. When the outcomes of these irreversible regions were assessed after reinjection and compared with rest-redistribution images, there was concordance of data regarding myocardial viability (normal/reversible or irreversible) in 72 of the 91 (79%) irreversible defects. Twenty of the 41 patients also underwent positron emission tomography at rest with [18F]fluorodeoxyglucose and [15O]water. In these patients, stress-redistribution-reinjection and rest-redistribution imaging provided concordant information regarding myocardial viability in 427 (72%) of 594 myocardial regions and discordance in 167 regions. However, when irreversible thallium defects were further analyzed according to the severity of the thallium defect in these discordant regions, 149 of 167 (89%) demonstrated only mild-to-moderate reduction in thallium activity (51% to 85% of normal activity), and positron emission tomography verified 98% of these regions to be metabolically active and viable. Thus, when the severity of thallium activity was considered within irreversible thallium defects, the concordance between stress-redistribution-reinjection and rest-redistribution imaging regarding myocardial viability increased to 94%.nnnCONCLUSIONSnThese data indicate that one of two imaging modalities, either stress-redistribution-reinjection or rest-redistribution imaging, may be used for identifying viable myocardium. However, if there are no contraindications to stress testing, stress-redistribution-reinjection imaging provides a more comprehensive assessment of the extent and severity of coronary artery disease by demonstrating regional myocardial ischemia without jeopardizing information on myocardial viability.

Regional left ventricular wall thickening. Relation to regional uptake of 18fluorodeoxyglucose and 201Tl in patients with chronic coronary artery disease and left ventricular dysfunction.

BackgroundIn previous studies comparing regional 201TI (201TI) and 18fluorodeoxyglucose (FDG) activity in patients with chronic coronary artery disease and left ventricular dysfunction, we hypothesized that regions with mild-to-moderate reduction in FDG activity and regions with mild-to-moderate irreversible 201TI defects after 3- to 4-hour redistribution represent viable myocardium. In the present study, regional FDG and 201TI activities were compared with regional systolic wall thickening by gated magnetic resonance imaging (MRI) to confirm the presence of viable myocardium in these territories Methods and ResultsTwenty-five patients with chronic stable coronary artery disease and left ventricular dysfunction (ejection fraction, 28±10) underwent exercise 201TI tomographic imaging (SPECT), using a reinjection protocol, positron emission tomography (PET) with FDG and H21550, and gated MRI. Matched SPECT, PET, and MRI tomograms were analyzed. From the PET data, 105 regions had matched reduction in FDG and blood flow, of which 69 regions had moderately reduced FDG uptake (50–79% uptake relative to a normal reference region) and 36 had severely reduced FDG uptake (<50% of normal activity). Regions with moderately reduced as compared with severely reduced FDG activity had greater end-diastolic wall thickness (9.4±2.6 versus 8.0±3.7 mm; p < 0.05) and regional systolic wall thickening (1.7±2.7 versus −0.7±2.1 mm; p < 0.01). From the SPECT data, 169 irreversible 201TI defedts after 3-4-hour redistribution were identified, of which 70 were mild (>65 to <85% of maximal 201TI activity), 52 were moderate (50–65% of maximal activity), and 47 were severe (<50% of maximal activity). Regional systolic wall thickening was greater in regions with normal 201TI uptake (3.3±2.3 mm) as compared with all other regions. Regions showing only mild or moderate irreversible defects at redistribution, however, showed wall thickening (2.4±2.4 and 2.2±2.5 mm, respectively), which was similar to that observed in regions with reversible 201TI defects (2.1±2.2 mm). Only regions with severe irreversible defects at redistribution showed absence of thickening (−0.1±2.9 mm, p < 0.01 versus all other groups). After 201TI reinjection, 12 of 47 (26%) regions with severe irreversible defects showed enhanced 201TI uptake. The impairment in regional systolic wall thickening was not significantly different between 201TI defects with and without enhanced 201TI uptake after reinjection. FDG activity, however, was present in all 12 regions (100%) with enhanced 201TI uptake after reinjection as compared with only five of 35 (14%) that were unchanged after reinjection (p < 0.01) ConclusionsTherefore, preserved wall thickness and systolic wall thickening in regions with moderate reduction in blood flow and FDG activity, and in irreversible 201TI defects that are only mild-to-moderate, provide additional evidence that such regions represent viable myocardium. Moreover, the finding of metabolic activity and 201TI uptake in regions with reduced blood flow and absent wall thickening provides clinical evidence of hibernating myocardium in humans.

Regional thallium uptake in irreversible defects. Magnitude of change in thallium activity after reinjection distinguishes viable from nonviable myocardium.

BACKGROUNDnThallium reinjection immediately after stress-redistribution imaging identifies ischemic but viable myocardium in as many as 50% of the regions characterized by conventional redistribution imaging as irreversibly injured. However, we have previously shown that some regions in which irreversible defects persist despite reinjection are metabolically active, and hence viable, by positron emission tomography. In the current study, we determined whether the severity of reduction in thallium activity within irreversible defects on redistribution images and the magnitude of change in regional thallium activity after reinjection can further discriminate viable from nonviable myocardium in such defects.nnnMETHODS AND RESULTSnWe studied 150 patients with coronary artery disease by exercise thallium tomography using the rest-reinjection protocol. The three sets of images (stress, redistribution, and reinjection) were then analyzed quantitatively. The increase in regional thallium activity from redistribution to reinjection was computed, normalized to the increase observed in a normal region, and termed differential uptake. Of the 175 myocardial regions designated to have irreversible thallium defects on conventional 3-4 hour redistribution images, 132 had only mild-to-moderate reduction in thallium activity (51-85% of normal activity), and 43 had severe reduction in thallium activity (less than or equal to 50% of normal activity). Thallium reinjection resulted in enhanced relative activity in 60 of 132 (45%) of the mild-to-moderate irreversible defects and 22 of 43 (51%) of the severe irreversible defects, leaving roughly half of these defects remaining irreversible after reinjection. However, in regions that appeared to remain irreversible despite reinjection, the magnitude of differential uptake differed between mild-to-moderate (74 +/- 14%) and severe (35 +/- 16%) irreversible defects (p less than 0.001). All regions with mild-to-moderate defects demonstrated greater than 50% differential uptake after reinjection. In contrast, all except two of the regions with severe irreversible defects demonstrated differential uptake of less than 50%. Fifteen patients also underwent positron emission tomography at rest with 18F-fluorodeoxyglucose (FDG) and 15O-water. FDG uptake was present in 91% of regions with mild-to-moderate reduction in thallium activity, and the results of differential uptake and FDG data were concordant in 81% of these regions.nnnCONCLUSIONSnThese data indicate that the magnitude of thallium uptake after reinjection differs between mild-to-moderate and severe irreversible defects on standard 3-4 hour redistribution images. The substantial differential uptake of thallium (greater than 50%) after reinjection in mild-to-moderate defects, even when relative thallium activity does not increase appreciably (and the defect appears to remain irreversible), coupled with preserved metabolic activity by positron emission tomography, supports the concept that such mild-to-moderate irreversible defects represent viable myocardium.

Metabolic evidence of viable myocardium in regions with reduced wall thickness and absent wall thickening in patients with chronic ischemic left ventricular dysfunction

Reduced end-diastolic wall thickness with absent systolic wall thickening has been reported to represent nonviable myocardium in patients with chronic coronary artery disease. To assess whether reduced regional end-diastolic wall thickness and absent wall thickening accurately identify nonviable myocardium, 25 patients with ischemic left ventricular dysfunction (ejection fraction at rest 27 +/- 10%) underwent positron emission tomography with oxygen-15-labeled water and 18fluorodeoxyglucose to assess metabolic activity and spin-echo gated nuclear magnetic resonance imaging to measure regional end-diastolic wall thickness and wall thickening. The presence of metabolic activity was defined as 18fluorodeoxyglucose uptake (corrected for partial volume) greater than 50% of that in normal regions. Of 355 myocardial regions evaluated, 266 were hypokinetic or normokinetic at rest and 89 were akinetic (that is, absent wall thickening). 18Fluorodeoxyglucose uptake was observed in 97% of the hypokinetic and normokinetic regions and in 74% of the akinetic regions. End-diastolic wall thickness was greater in akinetic regions with than in those without 18fluorodeoxyglucose uptake (11 +/- 4 vs. 7 +/- 3 mm, p less than 0.01). The highest values for sensitivity and specificity of end-diastolic wall thickness in predicting the absence of metabolic activity in akinetic regions were 74% and 79%, respectively, and corresponded to an end-diastolic threshold of 8 mm. However, the positive predictive accuracy was only 55% and did not improve for other end-diastolic wall thickness values. In all myocardial regions, there was only a weak correlation between 18fluorodeoxyglucose activity and either end-diastolic wall thickness (r = 0.17) or wall thickening (r = 0.32). Thus, metabolic activity is present in many regions with reduced end-diastolic wall thickness and absent wall thickening. These data indicate that assessment of regional anatomy and function may be inaccurate in distinguishing asynergic but viable myocardium from nonviable myocardium.

Clinical significance of reduced regional myocardial glucose uptake in regions with normal blood flow in patients with chronic coronary artery disease

OBJECTIVESnThe objective of this study was to assess the clinical significance of reduced regional fluorine-18 (18F) fluorodeoxyglucose uptake with normal flow in patients with chronic coronary artery disease.nnnBACKGROUNDnIn patients with ischemic left ventricular dysfunction, 18F-fluorodeoxyglucose uptake may be reduced in some myocardial regions despite normal flow. The significance of this finding is unclear and has not been investigated systematically.nnnMETHODSnTwenty-three patients with coronary artery disease and impaired ventricular function (mean ejection fraction [+/- 1 SD] 28 +/- 10%) underwent positron emission tomography with 18F-fluorodeoxyglucose and oxygen-15-labeled water at rest, exercise thallium-201 tomographic imaging with rest reinjection and gated magnetic resonance imaging to measure end-diastolic wall thickness and systolic wall thickening.nnnRESULTSnOf 168 regions with normal flow (> or = 0.7 ml/g per min), 125 (74%) had normal 18F-fluorodeoxyglucose uptake (98 +/- 10%), and the remaining 43 (26%) showed moderately reduced 18F-fluorodeoxyglucose uptake (69 +/- 8%). Systolic wall thickening was absent at rest in 14% of regions with normal 18F-fluorodeoxyglucose uptake compared with 32% of regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). Reversible thallium abnormalities were observed in 45 (36%) of 125 regions with normal 18F-fluorodeoxyglucose uptake compared with 27 (63%) of 43 regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). This difference was accounted for by a higher proportion of partially reversible defects in regions with reduced 18F-fluorodeoxyglucose uptake compared with regions with normal 18F-fluorodeoxyglucose uptake (42% vs. 18%, respectively, p < 0.01).nnnCONCLUSIONSnThus, regions with moderately reduced 18F-fluorodeoxyglucose uptake with normal flow occur commonly in patients with ischemic left ventricular dysfunction. The majority of these regions show impaired systolic function at rest and exercise-induced thallium abnormalities that are only partially reversible. These observations suggest that such regions represent an admixture of fibrotic and reversibly ischemic myocardium.

Improvement of the age-related impairment in left ventricular diastolic filling with verapamil in the normal human heart.

Left ventricular (LV) diastolic function declines with the normal aging process. Because these changes are related to impaired active LV relaxation as well as to structural alterations, we hypothesized that verapamil might improve LV filling in elderly normal subjects compared with young normal subjects. Methods and ResultsWe studied 27 normal volunteers (between 20 and 71 years old), with normal exercise tests and echocardiograms, by radionuclide angiography before and after 3 to 4 days of oral verapamil therapy. Indexes of global LV function were derived from analysis of background-corrected time-activity curves. Subjects were recruited from three age groups: young (26±4 years, n=10), middle-aged (46±5 years, n=9), and elderly (66±3 years, n=8). Baseline resting heart rate, blood pressure, peak systolic wall stress, and LV ejection fraction did not differ among groups. Baseline peak LV filling rate (expressed in fractional stroke volume per second) was reduced in the middle-aged group (5.8±1.2, P < .01) and the elderly group (4.3±1.0, P < .01) compared with the young group (7.8±1.2). With verapamil, resting heart rate, peak systolic wall stress, LV ejection fraction, and peak ejection rate did not change in any group. Peak filling rate increased in the middle-aged group (to 6.8±1.5 SV/s, P < .01) and the elderly group (to 5.7±1.0 SV/s, P < .01) but did not change in the young group (8.0±1.4 SV/s). Also, time to peak filling rate decreased with verapamil in the elderly group (from 185±31 to 147±15 milliseconds, P < .01). The magnitude of change in filling rate was correlated positively with age (r = .55, P < .005). ConclusionsVerapamil selectively enhances LV diastolic filling in middle-aged and elderly subjects, compared with young adults, without affecting systolic function. This observation supports the hypothesis that the impairment of LV filling accompanying the normal aging process is, at least in part, a reversible phenomenon.

Effects of regional systolic asynchrony on left ventricular global diastolic function in patients with coronary artery disease

Patients with coronary artery disease often have impaired left ventricular diastolic filling despite normal global systolic function. The influence of regional systolic asynchrony on diastolic function was assessed by radionuclide angiography in 60 patients with coronary artery disease and normal ejection fraction at rest: group 1 (n = 30) with normal wall motion at rest and group 2 (n = 30) with abnormal wall motion. Data were compared with those obtained from 19 normal volunteers. Age, heart rate, ejection fraction and echocardiographic end-diastolic dimension did not differ among the three groups. Peak filling rate in group 1 and group 2 was similar (2.5 +/- 0.5 and 2.3 +/- 0.6 end-diastolic counts/s, respectively) and significantly lower than that in the normal subjects (2.8 +/- 0.7 end-diastolic counts/s; p less than 0.01 vs. group 2, p less than 0.05 vs group 1). Time to peak filling rate was prolonged in group 2 (184 +/- 27 ms) compared with that in normal subjects (162 +/- 19 ms; p less than 0.01) and group 1 (172 +/- 15 ms; p less than 0.05). Left ventricular end-diastolic pressure was significantly higher in group 2 than in group 1 (14 +/- 7 vs. 10 +/- 5 mm Hg, respectively; p less than 0.05). Asynchrony was assessed by sector analysis of the radionuclide left ventricular region of interest. Diastolic asynchrony was similar in the two patient groups (30 +/- 23 ms in group 2, 26 +/- 16 ms in group 1) and was higher in both groups than in the normal subjects (16 +/- 8 ms; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional systolic function, myocardial blood flow and glucose uptake at rest in hypertrophic cardiomyopathy

Decreased 18fluorodeoxyglucose (FDG) uptake and blood flow at rest in the ventricular septum, as compared with the lateral wall, have been reported in mildly symptomatic patients with hypertrophic cardiomyopathy (HC). To assess whether regional metabolic heterogeneity in patients with HC is related to heterogeneous regional systolic function, 10 symptomatic patients (mean age 36 +/- 17 years) with HC and no coronary artery disease underwent positron emission tomography with oxygen-15-water and FDG, and nuclear magnetic resonance imaging at rest to assess regional anatomy and systolic function. Regional absolute blood flow was similar between the ventricular septum and lateral wall. In contrast, FDG activity was significantly greater in the lateral wall than in the septum (1,023 +/- 588 vs 767 +/- 388 nCi/ml, respectively; p < 0.01). However, regional systolic wall thickening was also significantly greater in the lateral wall than in the septum (5.3 +/- 4.3 vs 2.4 +/- 4.0 mm, respectively; p < 0.001). Patients were then divided into group A (n = 5) with similar regional wall thickening in the septum and lateral wall, and group B (n = 5) with greater thickening in the lateral wall than in the septum. In both groups, regional blood flow was similar between the septum and lateral wall. However, the regional septal-to-lateral FDG activity ratio was 0.97 +/- 0.31 in group A, and 0.74 +/- 0.25 in group B (p < 0.01); the ratio in group A did not differ from that in 5 normal subjects (1.02 +/- 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired left ventricular filling and regional diastolic asynchrony at rest in coronary artery disease and relation to exercise-induced myocardial ischemia

Impaired left ventricular (LV) diastolic filling at rest is frequently observed in patients with coronary artery disease (CAD) who have normal LV systolic function and no previous infarction. To test the hypothesis that abnormal diastolic function at rest might reflect the functional severity of CAD, as estimated by exercise-induced ischemia, the relation between regional and global LV diastolic function at rest and during exercise-induced ischemia was evaluated in 49 patients with radionuclide angiography. All patients had normal systolic function at rest. Group 1 (n = 26) patients manifested a normal ejection fraction response to exercise and group 2 (n = 23) patients an abnormal response. Data obtained from 22 age-comparable normal volunteers were used for comparison. Although regional and global diastolic function were not different between normal subjects and group 1 patients, peak filling rate was lower in group 2 patients than in normal subjects (2.5 +/- 0.8 vs 3.2 +/- 0.6 end-diastolic counts/s; p less than 0.01). Moreover, regional diastolic asynchrony, as assessed from the radionuclide data by using a regional sector analysis of the LV region of interest, was greater in group 2 patients (46 +/- 44 ms) than in both normal subjects (25 +/- 16 ms; p less than 0.05) and group 1 patients (23 +/- 16 ms; p less than 0.05). Thus, among patients with CAD and with normal LV systolic function at rest, impaired LV filling and regional asynchrony predict a greater degree of exercise-induced ischemia, suggesting a greater extent of jeopardized myocardium.

Comparison of exercise radionuclide angiography with thallium SPECT imaging for detection of significant narrowing of the left circumflex coronary artery

Although quantitation of exercise thallium tomograms has enhanced the noninvasive diagnosis and localization of coronary artery disease, the detection of stenosis of the left circumflex coronary artery remains suboptimal. Because posterolateral regional wall motion during exercise is well assessed by radionuclide angiography, this study determined whether regional dysfunction of the posterolateral wall during exercise radionuclide angiography is more sensitive in identifying left circumflex disease than thallium perfusion abnormalities assessed by single-photon emission computed tomography (SPECT). One hundred ten consecutive patients with CAD were studied, of whom 70 had a significant stenosis of the left circumflex coronary artery or a major obtuse marginal branch. Both regional function and segmental thallium activity of the posterolateral wall were assessed using visual and quantitative analysis. Left ventricular regional function was assessed objectively by dividing the left ventricular region of interest into 20 sectors; the 8 sectors corresponding to the posterolateral free wall were used to assess function in the left circumflex artery distribution. Similarly, using circumferential profile analysis of short-axis thallium tomograms, left ventricular myocardial activity was subdivided into 64 sectors; the 16 sectors corresponding to the posterolateral region were used to assess thallium perfusion abnormalities in the left circumflex artery territory. Qualitative posterolateral wall motion analysis detected 76% of patients with left circumflex coronary artery stenosis, with a specificity of 83%, compared with only 44% by qualitative thallium tomography (p less than 0.001) and a specificity of 92%. Whereas quantitation of thallium activity increased the sensitivity for detecting left circumflex coronary artery stenosis to 80% with a specificity of 55%, it did not achieve statistical significance when compared with qualitative wall motion analysis.(ABSTRACT TRUNCATED AT 250 WORDS)