Antonio Nappi

Technetium 99m-labeled tetrofosmin myocardial tomography in patients with coronary artery disease: Comparison between adenosine and dynamic exercise stress testing

BackgroundPharmacologic coronary vasodilation with adenosine, combined with myocardial scintigraphy, is a useful test for the diagnosis of coronary artery disease (CAD) in patients unable to exercise. It has been demonstrated recently that exercise 99mTc-labeled tetrofosmin cardiac imaging can be used for the detection of CAD. However, no data are available comparing 99mTc-labeled tetrofosmin adenosine and exercise tests in the same patients.Methods and ResultsThe results of adenosine and exercise 99mTc-labeled tetrofosmin myocardial tomography were compared in 41 patients (37 men and four women; mean age 53±8 years) with suspected or known CAD who underwent coronary angiography. All patients were submitted, on separate days, to three injections of 99mTc-labeled tetrofosmin (740 MBq intravenously): one at rest, one during bicycle exercise, and one during adenosine infusion (140 μg/kg/min for 6 minutes with injection of 99mTc-labeled tetrofosmin at 4 minutes). A total of 902 myocardial segments were analyzed quantitatively. One patient had normal coronary vessels, 19 patients had single-vessel CAD, 12 patients had two-vessel CAD, and nine patients had three-vessel CAD (>50% coronary stenosis) on coronary angiography. Adenosine induced a significant increase in heart rate (88±16 beats/min at peak vs 72±11 beats/min at rest; p<0.01). Systolic and diastolic blood pressure was not significantly different after adenosine infusion compared with rest. Double product was 22931 ± 7039 at peak exercise and 11229±3413 after adenosine (p<0.01). Agreement on the presence of abnormal single-photon emission computed tomography by adenosine and exercise was 100% by quantitative analysis. In all segments a significant relationship between exercise and adenosine 99mTc-99m-labeled tetrofosmin uptake was observed (r=0.90; p<0.001). Segmental agreement for regional 99mTc-labeled tetrofosmin uptake score between exercise and adenosine was observed in 737 (82%) of the 902 segments (kappa value of 0.66). Concordance between the two studies for identification of perfusion status was observed in 809 (90%) of the segments (kappa value of 0.80). Sensitivity and specificity for detection of stenosed vessels were not different for dynamic exercise stress testing and adenosine 99mTc-labeled tetrofosmin cardiac tomography.ConclusionsDespite different hemodynamic effects, adenosine and dynamic exercise 99mTc-labeled tetrofosmin single-photon emission computed tomographic imaging provides similar information in the diagnosis and localization of CAD.

Accuracy and repeatability of left ventricular systolic and diastolic function measurements using an ambulatory radionuclide monitor

The accuracy and repeatability of a new ambulatory radionuclide detector (VEST) for left ventricular systolic (ejection fraction) and diastolic (peak filling rate) measurements were assessed. Seventeen patients underwent equilibrium radionuclide angiography immediately before and immediately after a VEST study. The accuracy was evaluated at the beginning and at the end of the VEST studies. Limits of agreement for the ejection fraction were −1%: 2% at the beginning of the VEST study and −4% at the end. Limits of agreement for the peak filling rate were −0.6: 0.6 at the beginning of the VEST study and −0.7: 0.5 at the end. For both measurements the limits of agreement were well within the clinical range. Repeatability was evaluated in a second group of 11 patients who underwent VEST studies in 2 separate days. The coefficient of repeatability (twice the standard deviation of the differences between the 2 studies) was 13 for the ejection fraction and 0.4 for the peak filling rate. Thus, the VEST is an accurate and repeatable method to measure both the ejection fraction and peak filling rate.

Resting technetium-99m methoxyisobutylisonitrile cardiac imaging in chronic coronary artery disease : comparison with rest-redistribution thallium-201 scintigraphy

We studied 19 patients with angiographically proven coronary artery disease and left ventricular dysfunction (ejection fraction 33% ± 8%) by resting technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) and rest-redistribution thallium-201 cardiac imaging. Thallium and (99mTc-MIBI) studies were visually analysed. Of 285 segments, 203 (71%) had normal thallium uptake, 48 (17%) showed reversible thallium defects and 34 (12%) showed irreversible thallium defects. Of these 34 irreversible thallium defects, 19 (56%) were moderate and 15 (44%) were severe. Of the corresponding 285 segments, 200 (70%) had normal 99mTc-MIBI uptake, while 37 (13%) showed moderate and 48 (17%) showed severe reduction of 99 99mTc-MIBI uptake. Myocardial segmental agreement for regional uptake score between initial thallium and resting (99mTc-MIBI) images was 90% (κ=0.78). Segmental agreement between delayed thallium and resting 99Tc-MIBI images was 77% (κ=0.44). In particular, in 26 (9%) segments 99mTc-MIBI uptake was severely reduced while delayed thallium uptake was normal or only moderately reduced. These data suggest that although rest-redistribution thallium and resting (99mTc-MIBI) cardiac imaging provide concordant results in the majority of myocardial segments, some segments with severely reduced resting 99mTc-MIBI uptake may contain viable but hypoperfused myocardium. Thus, conclusions on myocardial viability based on 99mTc-MIBI uptake should be made with caution in chronic coronary artery disease.

Correlation between egfr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma

PurposeTo investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (TD) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC).MethodsA survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr), respectively. By obtaining the TD from the above analysis and the sub-sites’ potential doubling time (Tpot) from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif), was estimated.ResultsThe averages of TD were 77 (27-90)95% days in LEGFr and 8.8 (7.3-11.0)95% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites’ TD were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed.ConclusionsA higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck sub-site.

Adenosine coronary vasodilation quantitative technetium 99m methoxy isobutyl isonitrile myocardial tomography in the identification and localization of coronary artery disease

BackgroundExercise and dipyridamole 99mTc-labeled methoxy isobutyl isonitrile (MIBI) myocardial scintigraphy have been widely used for the diagnosis of coronary artery disease (CAD). However, only limited data on adenosine 99mTc-labeled MIBI cardiac imaging are currently available. This study was designed to assess the accuracy of quantitative adenosinerest 99mTc-labeled MIBI tomography in the diagnosis and localization of CAD.Methods and ResultsFifty-seven consecutive patients with suspected CAD who underwent coronary angiography and 22 normal volunteers were studied. All patients underwent 99mTc-labeled MIBI tomography after administration of adenosine (140 μg/kg intravenously for 6 minutes) and at rest. A total of 171 vascular coronary territories were analyzed quantitatively. All patients with CAD (≥50% luminal stenosis) (n=55) had abnormal 99mTc-labeled MIBI tomograms. The normalcy rate was 86% by quantitative analysis. Overall sensitivity, specificity, and diagnostic accuracy for detection of individual stenosed vessels were 84%, 87%, and 85%, respectively. In patients with one-vessel CAD (n=24), sensitivity and diagnostic accuracy in the detection of individual stenosed vessels were significantly (p<0.05) higher compared with patients with multivessel CAD (n=31). Moreover, 75% of patients with one-vessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in only one coronary artery territory, and 74% of patients with multivessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in two or more coronary artery territories. Sensitivity, specificity, and diagnostic accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=18) compared with those with previous myocardial infarction (n=39). In myocardial territories related to noninfarcted areas (n=124), sensitivity and specificity in the detection of stenosed vessels were 75% and 88%. In infarcted areas (n=47), sensitivity and specificity in the detection of stenosed vessels were 98% and 80% (differences not significant vs noninfarcted areas).ConclusionsAdenosine-controlled coronary vasodilation combined with quantitative 99mTc-labeled MIBI tomography is accurate for identifying patients with CAD and localizing individual stenosed coronary arteries.

Radionuclide Monitoring of Cardiac Adaptations to Volume Loading in Patients With Dilated Cardiomyopathy and Mild Heart Failure: Effects of Angiotensin-Converting Enzyme Inhibition

BACKGROUND Cardiac adaptations to volume overload have been poorly investigated in heart failure. The aim of this study was to assess dynamic left ventricular responses to acute volume loading by continuous radionuclide monitoring in patients with asymptomatic to mildly symptomatic left ventricular dysfunction. METHODS AND RESULTS Left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a radionuclide detector (Vest) before and during volume expansion (sodium chloride, 0.9%, 0.25 mL.kg-1.min-1 for 2 hours) in 10 patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I or II, ejection fraction < 50%). The patients were studied off treatment and after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of 11 age- and sex-matched healthy volunteers (N group) was also studied. In the N group, volume loading caused prompt and sustained increases of EDV, EF, and PFR (all P < .001), whereas ESV was progressively reduced (P < .001), and heart rate and blood pressure did not change. In contrast, in DCM, EDV showed a smaller increase than in the N group (two-way ANOVA: F = 5.98, P < .001), ESV increased (P < .001), and EF and PFR remained unchanged. After enalapril, the cardiac adaptations to volume loading were restored to normal. In particular, EDV, EF, and PFR increased (P < .001), and ESV was reduced (P < .001). In 6 additional DCM patients studied before and after 6 to 8 weeks of placebo treatment, left ventricular responses to volume loading remained unchanged. CONCLUSIONS Left ventricular dynamic adaptations to acute volume loading are compromised in patients with idiopathic DCM and mild heart failure. These impaired responses are ameliorated by treatment with enalapril.

Rest-injected thallium-201 redistribution and resting technetium-99m methoxyisobutylisonitrile uptake in coronary artery disease: relation to the severity of coronary artery stenosis

To compare rest-injected thallium-201 (Tl) redistribution and resting technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) myocardial uptake in chronic coronary artery disease (CAD), 15 patients with angiographically proven CAD and left ventricular (LV) dysfunction (ejection fraction 34%±9%) were studied. All patients underwent rest-redistribution Tl and resting 99mTc-MIBI cardiac imaging. Gated 99mTc-MIBI images were also acquired to assess regional LV wall motion (WM). Myocardial segments (n=225) were divided into three groups on the basis of the degree of coronary artery stenosis: group 1 (total occlusion, n=82), group 2 (50%–99% of stenosis, n=84) and group 3 (<50% of stenosis, n=59). WM was significantly worse in groups 1 and 2 compared to group 3 (P<0.001), but no difference was observed between groups 1 and 2. TI and 99mTc-MIBI uptake were significantly lower in groups 1 and 2 compared to group 3 (P < 0.001), and in group 1 compared to group 2 (P<0.001). When TI and 99mTc-MIBI uptake were directly compared, TI uptake was higher than 99mTc-MIBI uptake in group 1 (P<0.001), while no significant difference was observed in groups 2 and 3. Thus, both rest-injected TI redistribution and resting 99mTc-MIBI uptake reflected the severity of coronary artery stenosis in CAD. However, in myocardial segments with total coronary occlusion T1 uptake was significantly higher than 99mTc-MIBI uptake. Our data suggest that rest-injected Tl redistribution cardiac imaging may identify, more accurately than resting 99mTc-MIBI imaging, the presence of viable myocardium in chronic CAD, particularly when the coronary blood flow is severely impaired.

Relative protection from cerebral atherosclerosis of young patients with homozygous familial hypercholesterolemia

It is well known that hypercholesterolemia is correlated with coronary atherosclerosis, but no definite information is available on its association with cerebrovascular atherosclerosis. We studied 10 young patients (age 3-32 years) with homozygous familial hypercholesterolemia (FH), together with 3 normal relatives as healthy controls. Extra- and intracranial Doppler examination, MRI and cerebral blood flow by SPECT and 99mTc-HM-PAO were performed on all. Six out of 10 patients already had signs and symptoms of coronary heart disease, but all patients were free from ischemic brain lesions, as small as detectable at MRI, and had normal cerebral blood flow. Two patients presented significant stenosis of the carotid arteries at Doppler examination. Young patients with homozygous FH have early and clinically evident coronary atherosclerosis, while overt disease in the cerebral district is delayed despite the extremely elevated plasma cholesterol concentration. This was also confirmed by the autopsy of two patients, who died after the study and whose cerebral arteries were totally free from atherosclerotic lesions. The age, at which flow-reducing atherosclerotic lesions develop in hypercholesterolemic patients, differs with regard to the arterial district involved.

Quantitative Exercise Technetium-99m Tetrofosmin Myocardial Tomography for the Identification and Localization of Coronary Artery Disease

The aim of this study was to evaluate the accuracy of quantitative 1-day exercise-rest technetium-99m tetrofosmin tomography in the identification of patients with coronary artery disease (CAD) and in the detection of individual stenosed coronary vessels. Sixty-one patients with suspected CAD who underwent coronary angiography and 13 normal volunteers were studied. All patients were submitted to two i.v. injections of99mTc-tetrofosmin, one at peak exercise (370 MBq) and the other (1110 MBq) at rest 3 h after exercise (images 15–30 min after injection for both studies). All patients with CAD (≽0% luminal stenosis) (n=50) had an abnormal99mTc-tetrofosmin tomogram. Only one patient without significant coronary narrowing showed abnormal findings. Overall sensitivity, specificity and diagnostic accuracy in the detection of individual stenosed vessels were 77%, 93% and 85%, respectively. Sensitivity and diagnostic accuracy in the identification of individuals stenosed coronary vessels were significantly higher (P<0.05) in patients with single-vessel disease (n=21) than in those with multivessel disease (n=29). Sensitivity, specificity and accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=26) and in those with previous myocardial infarction (n=35). In myocardial territories related to non-infarcted areas (n=128), sensitivity and specificity in the detection of stenosed vessels were 70% and 95%, respectively. In infarcted areas (n=55), sensitivity and specificity in the detection of stenosed vessels were 85% (P=NS vs non-infarcted areas) and 75% (P<0.05 vs non-infarcted areas), respectively. Finally, sensitivity was significantly lower (P<0.05) in vascular territories supplied by vessels with moderate stenosis (50%–75%) than in those supplied by vessels with severe stenosis (>75%). The results of this study demonstrate that quantitative 1-day exercise-rest99mTc-tetrofosmin single-photon emission tomographic imaging is a suitable and accurate technique to identify patients with CAD and to detect individual stenosed coronary vessels.

Left ventricular dysfunction in coronary artery disease: Comparison between rest-redistribution thallium 201 and resting technetium 99m methoxyisobutyl isonitrile cardiac imaging

BackgroundWe compared rest-redistribution thallium 201 and resting technetium 99m methoxyisobutyl isonitrile (MIBI) cardiac imaging in 29 men with angiographically proven coronary artery disease and regional ventricular dysfunction. Left ventricular ejection fraction at radionuclide angiography was 35%±9%.Methods and ResultsRegional left ventricular wall motion was assessed on gated99mTc MIBI images according to a 3-point scale (0=normal, 1=hypokinetic, 2=akinetic or dyskinetic).201Tl and99mTc MIBI uptake values were analyzed quantitatively. A total of 435 myocardial segments were classified on the basis of wall motion analysis into three groups: group 1 (normal wall motion;n=201), group 2 (hypokinetic;n=132), and group 3 (akinetic or dyskinetic;n=102).201Tl and99mTc MIBI uptake values were significantly higher in groups 1 and 2 compared with group 3 (p<0.05) and in group 1 compared with group 2 (p<0.05). When201Tl and99mTc MIBI uptake values were directly compared, no significant differences in groups 1 and 2 were observed. In group 3,99mTc MIBI uptake (67%±14%) was significantly lower (p<0.001) than initial (72%±11%) and delayed201Tl uptake (73%±12%).ConclusionThus rest-redistribution201Tl and resting99mTc MIBI cardiac imaging reflect the severity of left ventricular dysfunction in coronary artery disease. However, in segments with severely impaired regional ventricular function,201Tl uptake is significantly higher than99mTc MIBI uptake.