Gender-related differences in side-effects and hemodynamic response to regadenoson in patients undergoing SPECT myocardial perfusion imaging.

PURPOSE: To evaluate differences in side-effects and hemodynamic response between men and women undergoing regadenoson-stress SPECT myocardial perfusion imaging (MPI). METHODS: The initial population of the study included 858 consecutive patients who underwent regadenoson-stress MPI at our institution. These patients underwent prospective assessment and classification of regadenoson-induced side-effects in six categories and recording of heart rate (HR) and blood pressure (BP) before and after regadenoson administration. From this initial population, after adjustment with 1:1 propensity matching using gender as the dependent variable and age, BMI, diabetes mellitus, hypertension, smoking, presence of coronary artery disease, LVEF, baseline systolic and diastolic blood pressure (BP) and HR, on-going use of cardio-active medications during test, and abnormal MPI scan as independent variables, a population of 279 pairs of opposite gender was formed and studied. RESULTS: Compared with men, women had a significantly higher rate of any side-effect (71% vs. 58%, p = 0.002), chest pain (23% vs. 12%, p < 0.001), gastrointestinal discomfort (20% vs. 12%, p = 0.01), dizziness (12% vs. 5%, p = 0.002), and headache (20% vs. 13%, p = 0.03) and similar rates of dyspnea and other side-effects. Women demonstrated a higher median HR-response compared with men (41% (- 8, 127) vs. 34% (- 5, 106), p = 0.001) while men demonstrated a lower median systolic BP response (- 3% (- 27, 48) vs. 0% (- 36, 68), p = 0.02) compared with women. CONCLUSIONS: Gender is independently associated with a differential response to regadenoson with regard to overall side-effects and HR-response. These observations have the potential of important management and prognostic implications respectively.

Adenosine stress myocardial perfusion imaging in octogenarians: Safety, tolerability, and long-term prognostic implications of hemodynamic response and SPECT-related variables.

BACKGROUND: Evaluation of tolerability, safety, and prognostic implications of adenosine stress myocardial perfusion imaging (MPI) in octogenarians. METHODS: 370 octogenarians (49% known coronary artery disease) were studied. Hemodynamic response, MPI-related data, and rest-left ventricular ejection fraction (LVEF) based on echocardiography were registered per patient, and prospective follow-up was performed to document all-cause death (ACD), cardiac death (CD), myocardial infarction (MI), and late revascularization. RESULTS: No deaths or MIs were observed during adenosine infusion or the short-term post-infusion period. 86% of patients were able to tolerate a 6-minute infusion. All side effects terminated spontaneously after infusion cessation, except for one case of pulmonary oedema. After 9.3 years, there were 124 ACDs, 62 CDs, 16 MIs, and 35 revascularizations. Differences between survival curves of summed stress score (SSS)-based risk groups were significant for all end points (P < .001). SSS and LVEF were independent predictors of all end points (P ≤ .01) and lung uptake of cardiac end points. ΔHR <10 bpm (OR = 1.78, P = .004) and inability to increase HR by >10 bpm and decrease systolic blood pressure by >10 mmHg (OR = 2, P = .02) during adenosine infusion were independent predictors of ACD and CD, respectively. Hemodynamic response variables, SSS, and lung uptake provided incremental prognostic value over pre-test data for ACD and CD. CONCLUSIONS: In octogenarians, adenosine stress MPI is well tolerated and provides effective long-term risk stratification.

Long-term prognostic implications of myocardial perfusion imaging in octogenarians: an all-comer, cohort study.

PURPOSE: Evaluation of the long-term prognostic value of myocardial perfusion imaging (MPI) in octogenarians. METHODS: Six hundred and twenty-nine octogenarians [51% previous myocardial infarction (MI) or revascularization] who underwent single-isotope MPI (78% 201Tl, 22% 99mTc-tetrofosmin) with exercise (38% Bruce, 2% leg ergometry) or pharmacologic (58% adenosine, 2% dobutamine) stress were studied. All patients had LVEF determined by echocardiography within 1 month from MPI. Myocardial perfusion scoring was performed on a 17-segment LV-model with a 5-point grading system and three summed stress score (SSS)-based risk categories were formed [high-(SSS > 12), low-(SSS < 4), medium]. Prospective follow-up was performed to document all-cause (ACD), cardiac death (CD), MI, and revascularization. Revascularization was used to censor follow-up in survival analysis regarding ACD, CD, and CD/MI. For analysis of the CD, MI, or late revascularization (LR) composite, only revascularizations within 3 months from MPI (early revascularizations) were used for censoring. RESULTS: After 9.3 years there were 187 ACDs, 86 CDs, 28 MIs, and 77 revascularizations, including 28 early revascularizations. Adjusting for LVEF and stress-modality type, SSS was identified as an independent predictor of ACD [HR 1.03 (1.01-1.05)], CD [HR 1.05 (1.03-1.08)], CD,MI [HR 1.05 (1.02-1.07)], and CD,MI or LR [HR 1.05 (1.03-1.07)] (p ≤ 0.001 in all cases). Increased lung uptake had independent prognostic value only for the CD, MI, or LR end-point [HR 3 (1.2-7.7), p = 0.02]. Survival modeling demonstrated that LVEF and SSS, but not non-perfusion scintigraphic data provided incremental prognostic value over pre-test available clinical and historical information for all end-points. Differences between Kaplan-Meier survival curves of SSS-based risk groups were significant for all end-points (p < 0.001 in all cases). CONCLUSIONS: In octogenarians, MPI provides effective long-term risk stratification, regardless of stress type used or underlying cardiac function.

Fast myocardial perfusion imaging with 99mTc in challenging patients using conventional SPECT cameras.

BACKGROUND: We attempted to validate the performance of a fast myocardial perfusion imaging (MPI) protocol in diagnostically challenging patients. METHODS: 78 patients with ΒΜΙ > 24.9, LVH or three vessels disease underwent two sequential gated-MPI studies. The first at 15 (Early Imaging, EI) and the second at 45 (Late Imaging, LI) minutes post 99mTc-injection, at both stress and rest. Counts over heart (H), liver (Liv) and subdiaphragmatic space (Sub) and image quality, and myocardial perfusion and function parameters were compared between the two protocols. Coronary angiography was performed within 2 months from MPI, and ROC analysis was used to compare the diagnostic accuracy for the detection of ≥50% diameter luminal stenosis. RESULTS: Quality was optimal-good in 93% of EI and 98% of LI studies (P = .12), H/Liv and stress H/Sub ratios were similar, but rest H/Sub ratio was lower in EI (P = .009). SSS [10 (0 to 46) vs 9 (0 to 36), P = .006] and SDS [3 (0 to 35) vs 2 (0 to 34), P = .02] were higher in EI protocol. LVEF, motion and thickening scores did not differ between the two protocols. A highly significant (P < .001) linear relationship with clinically negligible mean differences in Bland-Altman analysis was observed for all perfusion and function-related data. Sensitivity (EI 81%, LI 80%) and specificity (65% for both) did not differ (P = .23) between the two protocols. CONCLUSION: The fast protocol is technically feasible and diagnostically accurate compared to the established protocol in diagnostically challenging patients.

Risk stratification for large artery or chronic coronary artery disease-related ischemic stroke in octogenarians undergoing exercise stress myocardial perfusion imaging: A cohort study.

OBJECTIVES: To test, if in octogenarians, treadmill exercise with myocardial perfusion imaging (exercise-MPI) can risk stratify for large artery or chronic CAD-related ischemic stroke (LACCIS). METHODS: Exercise-MPI-related data of 237 octogenarians (55% prior MI or revascularization) without previous stroke were registered and prospective follow-up was performed to document LACCIS. LACCIS was defined as acute onset of neurological symptoms with CT/MRI findings of non-lacunar-type infarcts in the absence of atrial fibrillation or intracardiac embolic sources. RESULTS: After 7.3 years, 10 LACCIS were documented. SSS [HR 1.08 (1.02-1.13 95% CIs), SDS [HR 1.1 (1.04-1.16 95% CIs)], and non-sustained VT or transient AV block during exercise [HR 3.9 (1.7-9.0 95% CIs)] were predictors of LACCIS (P < .01 for all). A SSS threshold of 16 had 81% specificity for identification of future LACCIS and risk groups formed according to this cut-off had significantly different LACCIS-free survival (P = .015). CONCLUSION: Exercise-MPI in octogenarians can provide risk stratification markers for LACCIS.

Long-term prognostic value of myocardial perfusion imaging in octogenarians able to undergo treadmill exercise stress testing.

BACKGROUND: Although the use of myocardial perfusion imaging (MPI) for prognostic purposes in general population is well understood, its role in very elderly patients is not extensively studied. METHODS: 247 octgogenarians (79% male, 56% previous myocardial infarction-MI or revascularization) who underwent treadmill exercise testing (TET) with MPI were studied. TET and MPI-related data were registered per patient and prospective follow-up was performed to document all cause death (ACD), cardiac death (CD), non-fatal MI, and late revascularization (LR). Kaplan-Meier and Cox-regression analysis were used to compute event-free survival and identify significant predictors of these events. RESULTS: After 7.3 years there were 48 deaths, 17 CDs, 8 MIs, and 21 LRs. 69 patients were classified as high and 103 as low risk by SSS with annual cardiac mortality rates of 5% and 0.9%, respectively. Differences between survival curves of SSS-based risk groups were significant for ACD, CD, CD/MI, and CD/MI/LR. Summed stress (SSS) and difference scores were the only significant predictors of all endpoints. LVEF and transient ischemic LV dilatation were significant predictors of CD and CD/MI. LVEF and all MPI variables were associated with the CD, MI, and LR endpoint while only Duke treadmill score and angina severity demonstrated such a relationship among TET variables. CONCLUSIONS: In octogenarians, MPI provides effective long-term risk stratification for both hard (ACD, CD, CD/MI) and soft (CD/MI/LR) endpoints and should be preferred over simple TET.

Prognostic value of the Duke treadmill score in octogenarians undergoing myocardial perfusion imaging.

OBJECTIVES/BACKGROUND: Although Duke treadmill score (DTS) is the most widely used risk stratification method in younger patients undergoing exercise treadmill test (ETT) its specific value in the elderly is not established. METHODS: 137 patients aged ≥80 years who underwent ETT myocardial perfusion imaging (MPI) were studied. DTS and MPI (including summed stress scores, SSS) related data were registered per patient and follow up was performed to document cardiac death (CD), myocardial infarction (MI) and late (>3 months) revascularization (LR). Kaplan Meir and Cox regression survival analysis were employed to determine the prognostic value of DTS in relation to MPI data for these endpoints. RESULTS: After a median follow up duration of 6.7 years 28 deaths, 7 CDs, 4 non fatal MIs and 12 LRs were observed. Incidence rates of CD/MI were significantly different only between low and high risk SSS categories (p = 0.044). Risk groups by DTS had no significant differences in survival free of CD/MI (p = 0.743) in contrast to risk groups according to SSS (p = 0.026), while both DTS and SSS based risk groups had significantly different survival free of CD/MI or LR. SSS was a significant univariate predictor of both CD/MI (HR 1.088, p = 0.019) and CD/MI or LR (HR 1.095, p < 0.001), but DTS only of the latter endpoint (HR 0.909, p = 0.003). CONCLUSIONS: In octogenarians DTS was found to be a significant predictor of the LR related endpoint but not of the hard endpoint of CD/MI, in contrast to SSS which was a powerful predictor of both soft and hard cardiac endpoints.

Bone marrow stem cell adherence into old anterior myocardial infarction: a scintigraphic study using Tl-201 and Tc-99m-HMPAO.

AIM: The precise localization of bone marrow stem cells (SCs) into the necrotic tissue after intracoronary infusion (ICI) may be important for the therapeutic outcome. This study aims to examine the correlation between Tl-201 and Tc-99m-hexa-methyl-propylene-amine-oxime (HMPAO) images. METHODS: Thirteen patients, aged 36-62 years, with an old, nonviable, anterior myocardial infarction (MI) and reduced myocardial contractility (LVEF <40%), underwent ICI of selected CD133(+) and CD133(neg)CD34(+) SCs. One hour after the ICI, SPECT imaging with Tc-99m-HMPAO was performed in all patients and the acquired images were compared with the images obtained during the initial imaging for demonstration of viability (myocardial perfusion imaging with pharmacologic stress and Tl-201). Furthermore, two fused bull's eye images of Tc-99m-HMPAO and Tl-201 rest reinjection were created in six patients and regions of interest were set on Tl-201 and Tc-99m-HMPAO bull's eye images. RESULTS: The comparison of the two sets of images revealed an intense accumulation of the SCs in the infarcted area with absence of viability as assessed by Tl-201 reinjection images. In the subset of patients in whom fused bull's eye images were produced, the comparison demonstrated that the percentage of the infarcted area with SCs' adherence was 83.2 ± 17%. CONCLUSIONS: Tl-201 images are complementary with the respective Tc-99m-HMPAO ones, revealing a precise localization of SCs in the infarcted area. Tc-99m-HMPAO labeling of SCs is a reliable method for cell monitoring after ICI in nonviable myocardium after an anterior MI.

Disorders of the autonomic nervous system in patients with Brugada syndrome: a pilot study.

INTRODUCTION: The aim of this study was to examine autonomic disorders in patients with Brugada syndrome by performing a cardiac sympathetic innervation evaluation, a head-up tilt-test (HUT) and heart rate variability (HRV) analysis. METHODS AND RESULTS: We enrolled 20 patients with Brugada syndrome (mean age 42.5 +/- 8.8 years), 9 with spontaneous and 11 with an induced type 1 electrocardiogram (ECG) in the setting of symptoms and 20 age-matched controls. All subjects underwent a HUT with parallel measurements of plasma catecholamines and cortisol, a (123)I-metaiodobenzylguanidine single photon emission tomography, and HRV evaluation. Ten control subjects participated in the innervation portion of the study. The tilt-test with clomipramine challenge was positive in 15 of 20 (75%) patients (7 spontaneous, 8 induced) and in 1 in controls (P < 0.01). A sympathoadrenal imbalance was shown in positive tests. The pattern of innervation in all groups was heterogenic and similar to controls with a trend towards lower measurements in patients with a spontaneous type 1 ECG and a positive HUT. HRV analysis did not reveal any significant differences during day and night. Four patients (20%) had sustained ventricular arrhythmias during a follow-up of 31.1 +/- 8.6 months, but no correlations with innervation or response to tilting were found. CONCLUSION: A high susceptibility to vasovagal syncope was observed in patients with Brugada syndrome, which could be disease-related symptoms. Conversely, sympathetic innervation was observed to follow a physiological, heterogenic pattern; however, these factors did not have prognostic value for life-threatening arrhythmias.

Stress test with dual isotope studies for the documentation of classical ischemic preconditioning.

OBJECTIVES: We investigated whether myocardial perfusion imaging (MPI) can demonstrate the effect of classical preconditioning. METHODS: 21 patients with documented coronary artery disease (stenosis>or=70%) underwent two exercise stress tests (EST) with concomitant MPI, using TL-201 for the first and tetrofosmin-Tc-99m for the second. A third MPI was performed at rest, using Tc-99m. Total defect score was derived by summing tracer uptake in a 17 segments left ventricle model, graded on a 5-point scale. Tomographic images were also analyzed quantitatively, to derive the total defect size. RESULTS: Maximum ST depression did not differ significantly between the two EST (2.2+/-1 vs 2.2+/-1 mm, p=NS), however in the second EST longer times for onset of ischemic changes (228+/-94 vs 265+/-103 s, p=0.01) and appearance of angina (282+/-153 vs 328+/-177 s, p=0.04) were observed. Exercise perfusion abnormalities were significantly lower in the second MPI, in terms of both total defect score (19.2+/-11.5 vs 10+/-10.4, p<0.0001) and total defect size (28.3+/-16.9 vs 13.8+/-15.8, p<0.0001). CONCLUSION: Significant improvement in perfusion pattern was demonstrated in the second MPI, accompanied by delayed appearance of ischemic manifestations. The improvement in myocardial perfusion extends far beyond the changes that can be attributed to differences in myocardial uptake between tracers, reflecting the effect of classical preconditioning.

Treadmill exercise test with dual isotope scintigraphy documents the second window of preconditioning in humans.

BACKGROUND: In experimental studies, two windows of preconditioning have been identified, one lasting 1-2h and a second one (SWOP) starting 24h later and lasting 3-4 days. We sought to document SWOP in humans, using scintigraphy as an objective method of imaging. METHODS: Nineteen male patients, aged 62+/-7 years with documented coronary artery disease underwent two treadmill exercise tests (at baseline and 30 h later) and three tomographic perfusion studies (during the first exercise test, during the redistribution phase 4 h later and during the second exercise test 30 h later) with two different isotopes. Thallium-201 (TL) was used for the assessment of the first exercise and the redistribution phase, whereas technetium 99m tetrofosmin (TET) was used 30 h later for the evaluation of SWOP. Both exercise tests terminated at the same time-point. The distribution of TL and TET uptake was analyzed qualitatively using a 5-point scale on a 17-segment myocardial model. Perfusion score was derived by summing the uptake of all segments, while total perfusion defect by subtracting the polar map of the first exercise test from that of the second exercise test. RESULTS: Anginal symptoms were reported by 13 of 19 patients (68%) in the first test versus only 2 of 19 patients (11%) in the second one (p=0.001). The mean maximum ST segment depression was significantly reduced in the second test (from 1.58+/-0.73 to 0.82+/-1.07, p<0.01). Similarly, the perfusion score was reduced from 21.0+/-7.4 to 14.2+/-5.7 in the second test (p<0.01) and the total defect size from 24+/-16 to 12+/-14 (p<0.01). CONCLUSION: The myocardial perfusion improvement during the second exercise study confirms objectively the existence of SWOP in humans.

Correlation between R wave amplitude, exercise ischemic electrocardiographic indices and thallium-201 imaging defects in patients with known coronary artery disease.

We investigated the relation between R wave amplitude (RWA) and ST depression as well as the presence and extent of reversible ischemia in thallium-201 scanning in patients with known coronary artery disease (CAD) and found that RWA both at rest and during exercise testing (ET) correlates with the magnitude of ST depression in the same leads. Greater ST changes appear on leads with highest RWA. Thus lead selection strongly influences interpretation of ECG ischemic changes during ET in patients with CAD. An electrocardiographic result negative for ischemia in patients with low RWA should prompt the alternative use of echocardiography and scintigraphy.

Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution.

Central issues in intracoronary infusion (ICI) of bone marrow (BM)-cells to damaged myocardium for improving cardiac function are the cell number that is feasible and safe to be administrated as well as the retention of cells in the target area. Our study addressed these issues in eight patients with chronic ischemic cardiomyopathy undergoing ICI of selected BM-progenitors. We could immunomagnetically isolate 0.8 +/- 0.32 x 10(7) CD133(+) cells and 0.75 +/- 0.24 x 10(7) CD133(-)CD34(+) cells from 310 +/- 40 ml BM. After labeling these cells with (99m)Tc-hexamethylpropylenamineoxime, they were infused into the infarct-related artery without any complication. Scintigraphic images 1 (eight patients) and 24 hours (four patients) after ICI revealed an uptake of 9.2% +/- 3.6 and 6.8% +/- 2.4 of the total infused radioactivity in the infarcted area of the heart, respectively; the remaining activity was distributed mainly to liver and spleen. We conclude that through ICI of CD133(+) and CD133(-)CD34(+) BM-progenitors a significant number of them are preferentially attracted to and retained in the chronic ischemic myocardium.