388 research outputs found
Prediction of 8-year cardiovascular outcomes in patients with systemic arterial hypertension: Value of stress Tc-99m-tetrofosmin myocardial perfusion imaging in a high-risk cohort
Systemic arterial hypertension is a strong and prevalent cardiovascular risk factor. Currently, information on the very long-term prognostic value of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with systemic arterial hypertension is lacking. The aim of this study was to assess the value of stress Tc-99m-tetrofosmin MPI for the prediction of very long-term outcome in these patients. The study population consisted of 608 patients with systemic arterial hypertension who underwent exercise or dobutamine stress Tc-99m-tetrofosmin MPI for the assessment of known or suspected coronary artery disease. Follow-up was successful in 600 (99%) patients. The endpoints were all-cause mortality, cardiac death, nonfatal infarction, and coronary revascularization. Kaplan-Meier survival cures were constructed and univariate and multivariate analyses were performed to identify predictors of v The mean age of the patients was 59 +/- A 10 years, and 65% of them were male. MPI findings were normal in 301 patients (50%). Myocardial perfusion abnormalities were fixed in 162 (27%) and reversible in 137 (23%) patients. During a median 8.1-year follow-up, 241 (40%) patients died (121 cardiac deaths), 52 (9%) had a nonfatal myocardial infarction, and 128 (21%) underwent coronary revascularization. Survival curves in patients with a low vs a high summed difference score diverged up to 5 years Stress Tc-99m-tetrofosmin MPI provides incremental prognostic information for the prediction of cardiovascular outcome in patients with systemic arterial hypertension. Patients with normal stress MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the test is performed
Impact of clinically tested NEP/ACE inhibitors on tumor uptake of [111In-DOTA]MG11
Background: We have recently shown that treatment of mice with the neutral endopeptidase (NEP) inhibitor phosphoramidon (PA) improves the bioavailability and tumor uptake of biodegradable radiopeptides. For the truncated gastrin radiotracer [111In-DOTA]MG11 ([(DOTA)DGlu10]gastrin(10–17)), this method led to impressively high tumor-to-kidney ratios. Translation of this concept in the clinic requires the use of certified NEP inhibitors, such as thiorphan (TO) and its orally administered prodrug racecadotril (Race). Besides NEP, angiotensin-converting enzyme (ACE) has also been implicated in the catabolism of gastrin analogs. In the present study, we first compared the effects induced by NEP inhibition (using PA, TO, or Race) and/or by ACE inhibition (using lisinopril, Lis) on the biodistribution profile of [111In-DOTA]MG11 in mice. In addition, we compared the efficacy of PA and TO at different administered doses to enhance tumor uptake. Methods: [111In-DOTA]MG11 was coinjected with (a) vehicle, (b) PA (300 μg), (c) TO (150 μg), (d) Lis (100 μg), (e) PA (300 μg) plus Lis (100 μg), or (f) 30–40 min after intraperitoneal (ip) injection of Race (3 mg) in SCID mice bearing AR42J xenografts. In addition, [111In-DOTA]MG11 was coinjected with vehicle, or with progressively increasing amounts of PA (3, 30, or 300 μg) or TO (1.5, 15, and 150 μg) in SCID mice bearing twin A431-CCK2R(+/−) tumors. In all above cases, biodistribution was conducted at 4 h postinjection (pi). Results: During NEP inhibition, the uptake of [111In-DOTA]MG11 in the AR42J tumors impressively increased from 1.8 ± 1.0 % ID/g (controls) to 15.3 ± 4.7 % ID/g (PA) and 12.3 ± 3.6 % ID/g (TO), while with Race tumor values reached 6.8 ± 2.8 % ID/g. Conversely, Lis had no effect on tumor uptake and no additive effect when coinjected with PA. During the dose dependence study in mice, PA turned out to be more efficacious in enhancing tumor uptake of [111In-DOTA]MG11 in the CCK2R-positive tumors compared to equimolar amounts of TO. In all cases, renal accumulation remained low, resulting in notable increases of tumor-to-kidney ratios. Conclusions: This study has confirmed NEP as the predominant degrading enzyme of [111In-DOTA]MG11 and ruled out the involvement of ACE in the in vivo catabolism of the radiotracer. NEP inhibition with the clinically tested NEP
Safety, hemodynamic profile, and feasibility of dobutamine stress technetium myocardial perfusion single-photon emission CT imaging for evaluation of coronary artery disease in the elderly
OBJECTIVES: Cardiovascular disease is the leading cause of morbidity and
mortality in the elderly. The evaluation of coronary artery disease by
exercise stress testing is frequently limited by the patient's inability
to exercise. Although pharmacologic stress testing with dobutamine is an
alternative, the safety of dobutamine myocardial perfusion scintigraphy in
the elderly has not been previously studied. PATIENTS AND METHODS: We
studied the safety and feasibility of dobutamine (up to 40
microg/kg/min)-atropine (up to 1 mg) stress myocardial perfusion
scintigraphy using technetium single-photon emission CT imaging in 227
patients > or = 70 years old (mean +/- SD age, 75 +/- 4 years). A control
group of 227 patients < 70 years old (mean age, 55 +/- 11 years; matched
for gender, prevalence of previous infarction, beta-blocker therapy, and
severity of resting perfusion abnormalities) was studied to assess
age-related differences in the safety and the hemodynamic response. A
feasible test was defined as the achievement of the target heart rate
and/or an ischemic end point (angina, ST-segment depression, or reversible
perfusion abnormalities). RESULTS: No myocardial infarction or death
occurred during the test. The target heart rate was achieved more
frequently in the elderly patients (87% vs 79%; p < 0.05). The elderly
patients had a higher prevalence of supraventricular tachycardia (7% vs
1%; p < 0.005) and premature ventricular contraction (74% vs 32%; p <
0.005) during the test, as compared to the younger patients. There was a
trend to a higher prevalence of ventricular tachycardia (5% vs 2%) and
atrial fibrillation (3% vs 0.4%) in the elderly patients. Arrhythmias were
terminated spontaneously by termination of dobutamine infusion or by
administration of metoprolol. Independent predictors of supraventricular
tachyarrhythmias and ventricular tachycardia were older age (p < 0.001;
chi(2), 9.8) and myocardial perfusion defect score at rest (p < 0.01;
chi(2), 6.8) respectively, by using a multivariate analysis of clinical
and stress test variables. Elderly patients had a higher prevalence of
systolic BP drop > 20 mm Hg during the test (37% vs 12%; p < 0.05). The
test was terminated due to hypotension in 2% of the elderly patients and
in 1% of the control group. Age was the most powerful predictor of
hypotension (p < 0.005; chi(2), 10.3). The test was considered feasible in
216 elderly patients (95%) and in 209 patients of the control group (92%).
CONCLUSION: Dobutamine-atropine stress myocardial perfusion scintigraphy
is a highly feasible method for the evaluation of coronary artery disease
in the elderly. Elderly patients have a higher risk for developing
hypotension and supraventricular tachyarrhythmias during a dobutamine
stress test. However, dobutamine-induced hypotension is often asymptomatic
and rarely necessitates the termination of the test
Long-term prognostic value of dobutamine stress 99mTc-sestamibi SPECT: single-center experience with 8-year follow-up
PURPOSE: To determine the long-term prognostic value of dobutamine stress
technetium 99m (99mTc)-labeled sestamibi single photon emission computed
tomography (SPECT) in patients with limited exercise capacity. MATERIALS
AND METHODS: Clinical data and SPECT results were analyzed in 531
consecutive patients. Follow-up was successful in 528 (99.4%) patients; 55
underwent early revascularization and were excluded. Normal or abnormal
findings were considered in the absence or presence of fixed and/or
reversible perfusion defects. A summed stress score was calculated to
estimate the extent and severity of perfusion defects. Univariate and
multivariate Cox proportional hazards regression models were used to
identify independent predictors of late cardiac events. The incremental
value of myocardial perfusion scintigraphy over clinical variables in
predicting events was determined according to two models. The probability
of survival was calculated by using the Kaplan-Meier method. RESULTS:
Findings were abnormal in 312 patients. During 8.0 years +/- 1.5 of
follow-up (range, 4.5-10.6 years), cardiac death occurred in 67 patients
(total deaths, 165); nonfatal myocardial infarction, in 34; and late
revascularization, in 49. The annual rates for cardiac death, cardiac
death or infarction, and all events were 0.9%, 1.2%, and 1.5%,
respectively, after normal findings and 2.7%, 3.4%, and 4.4%,
respectively, after abnormal findings (P <.05). In a multivariable Cox
proportional hazards model, not only an abnormal finding but also the
summed stress score provided incremental prognostic information in
addition to clinical data. The hazard ratio for cardiac death was 1.09
(95% CI: 1.01, 1.18) per 1-unit increment of the summed stress score.
CONCLUSION: The incremental prognostic value of dobutamine stress
99mTc-sestamibi SPECT over clinical data was maintained over an 8-year
follow-up in patients with limited exercise capacity
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