Roberto Sciagrà

Rest technetium-99m sestmibi temography in combination with short-term administration of nitrates: Feasibility and reliability for prediction of postrevascularization outcome of asynergic territories

OBJECTIVES This study investigated the role of nitrate technetium-99m sestamibi imaging in predicting the postrevascularization outcome of chronically hypoperfused asynergic territories. BACKGROUND Rest technetium-99m sestamibi myocardial scintigraphy underestimates the presence of viable myocardium in asynergic territories. Stimulation that improves coronary blood flow could increase tracer uptake in hibernating territories. METHODS Nineteen patients with a previous myocardial infarction and left ventricular dysfunction scheduled for revascularization underwent quantitative technetium-99m sestamibi tomography under baseline conditions and during isosorbide dinitrate infusion. Global and regional function were assessed, respectively, before and after revascularization by radionuclide angiocardiography and two-dimensional echocardiography. RESULTS Seven patients (group A) showed postrevascularization regional function recovery, and 12 (group B) showed no significant changes. In group A, nitrate infusion induced a decrease in the extent of the global uptake defect ([mean +/- SD] -37.4 +/- 21.6% of baseline value); in group B, no change or a slight increase was observed (+5.8 +/- 8.4%, p < 0.0005 vs. group A). The nitrate-induced changes in the extent of uptake defect correlated with postrevascularization changes in ejection fraction (r = -0.94, SEE 7.6). After revascularization, 11 asynergic vascular territories showed improvement (hibernating), and 34 remained unchanged (fibrotic). With administration of nitrates, 10 hibernating territories had a decrease in the extent of uptake defect, whereas only 4 of 34 of the fibrotic territories showed a nitrate-induced uptake improvement. CONCLUSIONS Short-term administration of isosorbide dinitrate immediately before injection of technetium-99m sestamibi increases tracer uptake in some chronically hypoperfused asynergic territories. This finding correlates with the observation of post-revascularization functional recovery. Nitrate technetium-99m sestamibi myocardial scintigraphy could be a promising method for the noninvasive detection of viable hibernating myocardium.

Comparison of baseline-nitrate technetium-99m sestamibi with rest-redistribution thallium-201 tomography in detecting viable hibernating myocardium and predicting postrevascularization recovery.

OBJECTIVES This study aimed to define the optimal criteria for detecting viable myocardium with rest-redistribution thallium-201 (Tl-201) or baseline-nitrate technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) using discriminant analysis and to compare the accuracy of the two tracers in predicting postrevascularization recovery. BACKGROUND Rest-redistribution Tl-201 imaging is currently used for detection of myocardial viability, but the optimal variables for territory classification have not yet been defined. Although Tc-99m sestamibi is reportedly less effective than Tl-201, its reliability can be increased by injecting it during nitrate infusion. METHODS In 35 patients with left ventricular (LV) dysfunction, tracer activity within asynergic coronary territories was quantified on rest and redistribution Tl-201 and baseline and nitrate Tc-99m sestamibi SPECT. Asynergic territory viability was evaluated on the basis of the postrevascularization functional outcome. RESULTS Percent activity within asynergic territories was significantly influenced by their viability (p < 0.005) and the type of acquisition (p < 0.0001) but not by the tracer used. Discriminant analysis identified redistribution Tl-201 activity and nitrate-induced Tc-99m sestamibi activity change as the two most significant predictors of postrevascularization recovery. The discriminant function defined for Tl-201, including redistribution activity and reversibility, correctly classified 38 of 56 asynergic territories, whereas that for Tc-99m sestamibi, including nitrate-induced activity change and activity in nitrate images, correctly classified 43 territories. CONCLUSIONS Redistribution activity is more important than reversibility when differentiating viable from nonviable territories using rest-redistribution Tl-201. In Tc-99m sestamibi SPECT, nitrate-induced activity changes are particularly useful in identifying myocardial viability. Baseline-nitrate Tc-99m sestamibi SPECT appears no less effective than rest-redistribution Tl-201 in predicting postrevascularization recovery.

Single photon emission computed tomography with technetium-99m hexakis 2-methoxyisobutyl isonitrile in acute myocardial infarction before and after thrombolytic treatment : assessment of salvaged myocardium and prediction of late functional recovery

Single photon emission computed tomography (SPECT) with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a method to evaluate the results of intravenous thrombolytic treatment in 14 patients (11 men and 3 women) with acute myocardial infarction admitted to the coronary care unit within 4 h of the onset of symptoms. All patients received an injection of 740 MBq of the tracer before starting the thrombolytic therapy, and isonitrile tomography was performed 3 to 4 h later. The tomographic study was repeated 5 days after the acute event. The results of thrombolytic treatment were independently evaluated taking into account the clinical, electrocardiographic (ECG) and enzymatic data and the findings of left ventricular and coronary angiography. Furthermore, all patients were studied with two-dimensional echocardiography on admission, 5 days later and 1 month later. The site and extent of the perfusion defects on admission scintigraphy were consonant with the ECG and echocardiographic findings. A good correlation could be established between the 5 day scintigraphic estimate of infarct dimension and the enzymatic infarct size (r = 0.907, p less than 0.00002). The comparison between pre- and postthrombolytic treatment images enabled the identification of successful and unsuccessful reperfusion even in patients whose other noninvasive findings were inconclusive. Finally, the reduction in defect size predicted late functional improvement that was demonstrated by echocardiography performed 1 month later (r = 0.89, p less than 0.00005). The results of the study suggest the feasibility and the possible usefulness of isonitrile tomography in demonstrating the presence and size of myocardial damage and in assessing the extent of myocardial salvage after thrombolytic therapy in acute myocardial infarction.

Microvascular Function Is Selectively Impaired in Patients With Hypertrophic Cardiomyopathy and Sarcomere Myofilament Gene Mutations

OBJECTIVES The purpose of this study was to assess myocardial blood flow (MBF) using positron emission tomography in patients with hypertrophic cardiomyopathy (HCM) according to genetic status. BACKGROUND Coronary microvascular dysfunction is an important feature of HCM, associated with ventricular remodeling and heart failure. We recently demonstrated the increased prevalence of systolic dysfunction in patients with HCM with sarcomere myofilament gene mutations and postulated an association between genetic status and coronary microvascular dysfunction. METHODS Maximum MBF (intravenous dipyridamole, 0.56 mg/kg; Dip-MBF) was measured using (13)N-labeled ammonia in 61 patients with HCM (age 38 ± 14 years), genotyped by automatic DNA sequencing of 8 myofilament-encoding genes (myosin-binding protein C, beta-myosin heavy chain, regulatory and essential light chains, troponin T, troponin I, troponin C, alpha-tropomyosin, and alpha-actin). In 35 patients, cardiac magnetic resonance imaging was performed. RESULTS Fifty-three mutations were identified in 42 of the 61 patients (genotype positive; 69%). Despite similar clinical profiles, genotype-positive patients with HCM showed substantially lower Dip-MBF compared with that of genotype-negative patients (1.7 ± 0.6 ml/min/g vs. 2.4 ± 1.2 ml/min/g; p < 0.02). A Dip-MBF <1.5 ml/min/g had 81% positive predictive value for genotype-positive status and implied a 3.5-fold independent increase in likelihood of carrying myofilament gene mutations (hazard ratio: 3.52; 95% confidence interval: 1.05 to 11.7; p = 0.04). At cardiac magnetic resonance imaging, the prevalence of late gadolinium enhancement was greater in genotype-positive patients (22 of 23 [96%] compared with 8 of 12 [67%] genotype-negative patients; p = 0.038). CONCLUSIONS Patients with HCM with sarcomere myofilament mutations are characterized by more severe impairment of microvascular function and increased prevalence of myocardial fibrosis, compared with genotype-negative individuals. These findings suggest a direct link between sarcomere gene mutations and adverse remodeling of the microcirculation in HCM, accounting for the increased long-term prevalence of ventricular dysfunction and heart failure in genotype-positive patients.

Prognostic implications of Tc-99m sestamibi viability imaging and subsequent therapeutic strategy in patients with chronic coronary artery disease and left ventricular dysfunction.

OBJECTIVES The aim of the study was to verify the prognostic implications of viability detection using baseline-nitrate sestamibi imaging in patients with left ventricular (LV) dysfunction due to chronic coronary artery disease (CAD) submitted to different therapeutic strategies. BACKGROUND The prognostic meaning of preserved viability in these patients is still debated. Sestamibi is increasingly used for myocardial perfusion scintigraphy and is being accepted also as viability tracer, but no data are available about the relationship between viability in sestamibi imaging, subsequent treatment, and patients outcome. METHODS Follow-up data were collected in 105 CAD patients with LV dysfunction who had undergone baseline-nitrate sestamibi perfusion imaging for viability assessment and had been later treated medically (group 1), or submitted to revascularization, which was either complete (group 2A) or incomplete (group 2B). RESULTS Eighteen hard events (cardiac death or nonfatal myocardial infarction) were registered during the follow-up. A significantly worse event-free survival curve was observed in the patients of group 1 (p < 0.0002) and group 2B (p < 0.03) compared to those of group 2A. Using a Cox proportional hazard model, the most powerful prognostic predictors of events were the number of nonrevascularized asynergic segments with viability in sestamibi imaging (p < 0.003, risk ratio [RR] = 1.4), and the severity of CAD (p < 0.02, RR = 1.28). CONCLUSIONS Viability detection in sestamibi imaging has important prognostic implications in CAD patients with LV dysfunction. Patients with preserved viability kept on medical therapy or submitted to incomplete revascularization represent high-risk groups.

Diagnostic accuracy of peak exercise echocardiography in coronary artery disease: Comparison with thallium-201 myocardial scintigraphy

To evaluate the accuracy of exercise two-dimensional echocardiography for the recognition of coronary artery disease, 53 patients (46 men and 7 women, age range 35 to 69 years) without either previous myocardial infarction or resting wall motion abnormalities, were studied. According to coronary angiography 26 had normal coronary arteries, 14 had one-vessel, seven had two-vessel, and six had three-vessel disease. After withdrawal of any therapy, all patients underwent a single exercise stress test with a stress table during which cine-loop digitized echocardiography was acquired and 74 MBq of thallium-201 (TI-201) were injected. Echocardiographic images were evaluated at rest and at peak exercise. Three-view planar scintigraphic images were collected immediately after exercise and 4 hours later. For the overall recognition of coronary artery disease, exercise electrocardiography had 77.8% sensitivity and 65.4% specificity; myocardial scintigraphy had 100% sensitivity and 92.3% specificity; and exercise echocardiography had 92.6% sensitivity and 96.2% specificity (both NS versus myocardial scintigraphy). Global accuracy was 71.7% for exercise electrocardiography, 94.3% for stress echocardiography, and 96.2% for myocardial scintigraphy. For the classification of the individual involved coronary arteries, the sensitivity of myocardial scintigraphy was 84.8% and that of exercise echocardiography was 63% (p less than 0.01); the related specificities were 98% and 98.2% respectively (NS). It may be concluded that exercise echocardiography is highly accurate for the recognition of coronary artery disease, whereas it appears less sensitive in the identification of the involved vessels, particularly in patients with multivessel disease.

Head-to-head comparison of exercise stress testing, pharmacologic stress echocardiography, and perfusion tomography as first-line examination for chest pain in patients without history of coronary artery disease

BackgroundTo overcome the relatively low accuracy of exercise stress testing (EST) in detecting coronary artery disease (CAD), both echocardiography and perfusion scintigraphy have been evaluated in conjunction with pharmacologic stress, but there is still uncertainty of the relative value of these tests as possible first-line examinations for suspected CAD. This study evaluated the accuracy of EST, dipyridamole and dobutamine stress echocardiography (DIP-ECHO, DOB-ECHO), and dipyridamole and dobutamine technetium 99m sestamibi tomography (DIP-MIBI, DOB-MIBI) for the detection of CAD in patients evaluated for the first time because of chest pain.Methods and resultsSixty patients underwent EST, DIP-ECHO, DOB-ECHO, DIP-MIBI, and DOB-MIBI. Echocardiographic images were acquired simultaneously with sestamibi injections, and the scintigraphic images were collected 1 hour later. Coronary angiography was performed within 15 days. Out of 33 patients with significant (>70%) coronary stenoses, 19 (58%) were correctly identified by EST, 18 (55%) by DIP-ECHO, 20 (61%) by DOB-ECHO, 32 (97%) by DIP-MIBI, and 30 (91%) by DOB-MIBI (p<0.005 for MIBI vs EST and ECHO). The specificity of EST was 67% (p<0.05 vs ECHO and MIBI), 96%, 96%, 89%, and 81%, respectively. Of the 62 stenotic coronary arteries, 20 (32%) were correctly identified by DIP-ECHO, 24 (39%) by DOB-ECHO, 48 (77%) by DIP-MIBI, and 45 (73%) by DOB-MIBI. The sensitivity of the imaging techniques in predicting the presence of multivessel disease was 14% and 29% for DIP and DOB-ECHO compared with 48% and 57% for DIP and DOB-MIBI.ConclusionsOur results confirm the limited reliability of EST in detecting CAD and the good diagnostic value of DIP and DOB-MIBI. Conversely, the lower sensitivity and the poorer capability to recognize multivessel CAD do not support the role of either DIP or DOB-ECHO as first-line examination for suspected CAD.

Spatial Relationship Between Coronary Microvascular Dysfunction and Delayed Contrast Enhancement in Patients with Hypertrophic Cardiomyopathy

To clarify the spatial relationship between coronary microvascular dysfunction and myocardial fibrosis in hypertrophic cardiomyopathy (HCM), we compared the measurement of hyperemic myocardial blood flow (hMBF) by PET with the extent of delayed contrast enhancement (DCE) detected by MRI. Methods: In 34 patients with HCM, PET was performed using 13N-labeled ammonia during hyperemia induced by intravenous dipyridamole. DCE and systolic thickening were assessed by MRI. Left ventricular myocardial segments were classified as with DCE, either transmural (DCE-T) or nontransmural (DCE-NT), and without DCE, either contiguous to DCE segments (NoDCE-C) or remote from them (NoDCE-R). Results: In the group with DCE, hMBF was significantly lower than in the group without DCE (1.81 ± 0.94 vs. 2.13 ± 1.11 mL/min/g; P < 0.001). DCE-T segments had lower hMBF than did DCE-NT segments (1.43 ± 0.52 vs. 1.91 ± 1 mL/min/g, P < 0.001). Similarly, NoDCE-C segments had lower hMBF than did NoDCE-R (1.98 ± 1.10 vs. 2.29 ± 1.10 mL/min/g, P < 0.01) and had no significant difference from DCE-NT segments. Severe coronary microvascular dysfunction (hMBF in the lowest tertile of all segments) was more prevalent among NoDCE-C than NoDCE-R segments (33% vs. 24%, P < 0.05). Systolic thickening was inversely correlated with percentage transmurality of DCE (Spearman ρ = −0.37, P < 0.0001) and directly correlated with hMBF (Spearman ρ = 0.20, P < 0.0001). Conclusion: In myocardial segments exhibiting DCE, hMBF is reduced. DCE extent is inversely correlated and hMBF directly correlated with systolic thickening. In segments without DCE but contiguous to DCE areas, hMBF is significantly lower than in those remote from DCE and is similar to the value obtained in nontransmural DCE segments. These results suggest that increasing degrees of coronary microvascular dysfunction might play a causative role for myocardial fibrosis in HCM.

Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodelling: the TIPTOP trial

AIMS Experimental studies suggest that doxycycline attenuates post-infarction remodelling and exerts protective effects on myocardial ischaemia/reperfusion injury. However, the effects of the drug in the clinical setting are unknown. The aim of this study was to examine the effect of doxycycline on left ventricular (LV) remodelling in patients with acute ST-segment elevation myocardial infarction (STEMI) and LV dysfunction. METHODS AND RESULTS Open-label, randomized, phase II trial. Immediately after primary percutaneous coronary intervention, patients with STEMI and LV ejection fraction < 40% were randomly assigned to doxycycline (100 mg b.i.d. for 7 days) in addition to standard therapy, or to standard care. The echo LV end-diastolic volumes index (LVEDVi) was determined at baseline and 6 months. (99m)Tc-Sestamibi-single-photon emission computed tomography infarct size and severity were assessed at 6 months. We calculated a sample size of 110 patients, assuming that doxycycline may reduce the increase in the LVEDVi from baseline to 6 months > 50% compared with the standard therapy (statistical power > 80% with a type I error = 0.05). The 6-month changes in %LVEDVi were significant smaller in the doxycycline group than in the control group [0.4% (IQR: -16.0 to 14.2%) vs.13.4% (IQR: -7.9 to 29.3%); P = 0.012], as well as infarct size [5.5% (IQR: 0 to 18.8%) vs. 10.4% (IQR: 0.3 to 29.9%) P = 0.052], and infarct severity [0.53 (IQR: 0.43-0.62) vs. 0.44 (IQR: 0.29-0.60), P = 0.014], respectively. CONCLUSION In patients with acute STEMI and LV dysfunction, doxycycline reduces the adverse LV remodelling for comparable definite myocardial infarct size (NCT00469261).

Usefulness of Dobutamine Tc-99m Sestamibi-Gated Single-Photon Emission Computed Tomography for Prediction of Left Ventricular Ejection Fraction Outcome After Coronary Revascularization for Ischemic Cardiomyopathy

Gated single-photon emission computed tomography (SPECT) imaging allows analysis of myocardial perfusion and assessment of baseline global and regional left ventricular (LV) function and their changes during low-dose dobutamine infusion. The study examined whether the changes in LV ejection fraction induced by dobutamine and evaluated using technetium-99m sestamibi- gated SPECT predict the evolution of ejection fraction after revascularization in patients with ischemic cardiomyopathy. Thirty-seven patients underwent resting and dobutamine nitrate-enhanced sestamibi-gated SPECT before revascularization and baseline-resting sestamibi gated SPECT after intervention to assess global functional changes. A postrevascularization improvement in ejection fraction > or =5 U was defined as significant. At follow-up, ejection fraction increased significantly in 19 patients. According to receiver-operating characteristic curve analysis, an increase in ejection fraction > or =5 U during dobutamine was the optimal cutoff value for predicting a significant postrevascularization improvement, with 79% sensitivity, 78% specificity, and 78% accuracy. A significant correlation was found between dobutamine and postrevascularization ejection fraction (r = 0.85; p <0.0001). The increase in ejection fraction during dobutamine is a good predictor of an improvement in ejection fraction after revascularization. This represents another important diagnostic contribution obtained using gated SPECT imaging for the assessment of myocardial viability in patients with ischemic cardiomyopathy.