CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis.

The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05), when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR) domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC) was synthesized and labeled with (111)InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases.

Association between perivascular inflammation and downstream myocardial perfusion in patients with suspected coronary artery disease.

AIMS: To investigate the association between pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation derived from coronary computed tomography angiography (CTA) and coronary flow reserve (CFR) by positron emission tomography (PET) in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: PCAT CT attenuation was measured in proximal segments of all major epicardial coronary vessels of 105 patients with suspected CAD. We evaluated the relationship between PCAT CT attenuation and other quantitative/qualitative CT-derived anatomic parameters with CFR by PET. Overall, the mean age was 60 ± 12 years and 93% had intermediate pre-test probability of obstructive CAD. Obstructive CAD (≥50% stenosis) was detected in 37 (35.2%) patients and impaired CFR (<2.0) in 32 (30.5%) patients. On a per-vessel analysis (315 vessels), obstructive CAD, non-calcified plaque volume, and PCAT CT attenuation were independently associated with CFR. In patients with coronary calcium score (CCS) <100, those with high-PCAT CT attenuation presented significantly lower CFR values than those with low-PCAT CT attenuation (2.47 ± 0.95 vs. 3.13 ± 0.89, P = 0.003). Among those without obstructive CAD, CFR was significantly lower in patients with high-PCAT CT attenuation (2.51 ± 0.95 vs. 3.02 ± 0.84, P = 0.021). CONCLUSION: Coronary perivascular inflammation by CTA was independently associated with downstream myocardial perfusion by PET. In patients with low CCS or without obstructive CAD, CFR was lower in the presence of higher perivascular inflammation. PCAT CT attenuation might help identifying myocardial ischaemia particularly among patients who are traditionally considered non-high risk for future cardiovascular events.

Cardiac resynchronization therapy evaluated by myocardial scintigraphy with 99mTc-MIBI: changes in left ventricular uptake, dyssynchrony, and function.

PURPOSE: (99m)Tc-MIBI gated myocardial scintigraphy (GMS) evaluates myocyte integrity and perfusion, left ventricular (LV) dyssynchrony and function. Cardiac resynchronization therapy (CRT) may improve the clinical symptoms of heart failure (HF), but its benefits for LV function are less pronounced. We assessed whether changes in myocardial (99m)Tc-MIBI uptake after CRT are related to improvement in clinical symptoms, LV synchrony and performance, and whether GMS adds information for patient selection for CRT. METHODS: A group of 30 patients with severe HF were prospectively studied before and 3 months after CRT. Variables analysed were HF functional class, QRS duration, LV ejection fraction (LVEF) by echocardiography, myocardial (99m)Tc-MIBI uptake, LV end-diastolic volume (EDV) and end-systolic volume (ESV), phase analysis LV dyssynchrony indices, and regional motion by GMS. After CRT, patients were divided into two groups according to improvement in LVEF: group 1 (12 patients) with increase in LVEF of 5 or more points, and group 2 (18 patients) without a significant increase. RESULTS: After CRT, both groups showed a significant improvement in HF functional class, reduced QRS width and increased septal wall (99m)Tc-MIBI uptake. Only group 1 showed favourable changes in EDV, ESV, LV dyssynchrony indices, and regional motion. Before CRT, EDV, and ESV were lower in group 1 than in group 2. Anterior and inferior wall (99m)Tc-MIBI uptakes were higher in group 1 than in group 2 (p<0.05). EDV was the only independent predictor of an increase in LVEF (p=0.01). The optimal EDV cut-off point was 315 ml (sensitivity 89%, specificity 94%). CONCLUSION: The evaluation of EDV by GMS added information on patient selection for CRT. After CRT, LVEF increase occurred in hearts less dilated and with more normal (99m)Tc-MIBI uptake.

Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT.

BACKGROUND AND PURPOSE: Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel-based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. METHODS: rCBF was evaluated with 99mTc-single-photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel-based analyses of rCBF data were conducted using the statistical parametric mapping software. RESULTS: Significant rCBF reductions in HF patients relative to controls (P<.05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between-group rCBF differences had been identified. CONCLUSIONS: These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and suggest that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.

Myocardial blood flow assessment with 82rubidium-PET imaging in patients with left bundle branch block.

OBJECTIVES: Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease. OBJECTIVE: We sought to investigate rubidium-82 (82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block. METHODS: Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress 82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII). RESULTS: Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001). CONCLUSION: The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by 82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.

Strategy for identifying an efficient dosage of beta-blocker for elderly patients with myocardial ischemia and preserved left ventricular function.

OBJECTIVE: To assess the strategy of titration for prescribing an efficient dosage of propranolol to reduce myocardial ischemia in the elderly. METHODS: The study comprised 14 elderly men (73.6 +/- 5.3 years) with stable coronary heart disease documented on coronary cineangiography, ischemic response to exercise testing, and preserved left ventricular function. Titration was performed to identify the dosage of propranolol that would cause a 15% reduction in heart rate at the end of a 50 W load (corresponding to normal daily activities in the elderly) in weekly exercise tests. Synchronous scintigraphic study of the cardiac chambers was performed at rest and during exercise prior to and after propranolol use. RESULTS: The reductions in heart rate with the 50 W load and at rest were similar (21% vs 20%; P=0.5100). Propranolol improved the duration of exercise (12.2 +/- 2.0 min vs 13.1 +/- 1.8 min; P=0.0313) and abolished the changes in the ST segment induced by exercise in 8 (57%) patients. At rest, the ejection fraction was not modified by the beta-blocker. During maximum exercise, propranolol reduced the end-systolic volume index and increased ejection fraction. CONCLUSION: The strategy of using beta-blockers to reduce heart rate by 15% with a 50 W load is safe and beneficial in the elderly patient with myocardial ischemia and preserved ventricular function. The dose of beta-blocker used reduced myocardial ischemia and improved tolerance to exercise without hampering ventricular performance during maximum exercise.

Early postnatal rat ventricle resection leads to long-term preserved cardiac function despite tissue hypoperfusion.

One-day-old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long-term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End-Diastolic Pressure-Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long-term preservation of cardiac function despite tissue hypoperfusion.

2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography initial staging impacts on survival in Hodgkin lymphoma.

AIM: To assess the prognostic value and risk classification improvement of metabolic staging (MS) with Initial 2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography (FDG-PET) in initial staging of Hodgkin's Lymphoma (HL) patients to predict 5 years overall survival (5y-OS) and event free survival (EFS). METHODS: A total of 275 patients were included in this retrospective study, 155 patients were staged with conventional anatomical staging (AS), and 120 also submitted to MS (FDG-PET). Prognostic analysis compared 5y-OS and 5y-EFS of patients staged with AS and MS. Risk-adjusted models incorporated clinical risk factors, computed tomography and FDG-PET staging. RESULTS: During the follow up of 267 evaluated patients, 220 (122 AS and 98 MS) achieved complete remission after first-line therapy (median follow-up: 70 ± 29 mo), treatment failure occurred in 79 patients and 34 died. The 5y-EFS for early vs advanced disease in AS patients was 79.3% and 66.7%, and 85.6% and 53.6% in MS patients, respectively (P < 0.01). The 5y-OS for early and advanced disease with AS was 91.3% and 81.5%, and 97.5% and 80.7% for patients staged with MS, respectively. Cox proportional hazards analysis demonstrated that FDG-PET added significant prognostic information and improved risk prediction (P = 0.02). CONCLUSION: Initial staging FDG-PET could be used as an accurate and independent predictor of OS and EFS in HL, with impact in 5y-EFS and OS.

FDG-PET in Lymphoma: Nuclear Medicine Perspective.

Positron emission tomography (PET) is a sectional molecular imaging procedure that allows evaluation of the metabolism at a molecular and cellular level. For a PET scan, the patient is injected with a radiotracer, such as (18)F-fluorodeoxyglucose (FDG). FDG PET-computed tomography has become an established modality for metabolic staging and plays an important role in the major steps of evaluation and treatment of most lymphoma subtypes, with significant impact in the initial staging, posttherapy evaluation, and suspect of relapse of disease. However, whenever the information of PET results is translated to changing treatment, especially in cases of further treatment, biopsy confirmation should always be made when possible.

Consistency of FDG-PET accuracy and cost-effectiveness in initial staging of patients with Hodgkin lymphoma across jurisdictions.

INTRODUCTION: Two hundred ten patients with newly diagnosed Hodgkin's lymphoma (HL) were consecutively enrolled in this prospective trial to evaluate the cost-effectiveness of fluorine-18 ((18)F)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scan in initial staging of patients with HL. METHODS: All 210 patients were staged with conventional clinical staging (CCS) methods, including computed tomography (CT), bone marrow biopsy (BMB), and laboratory tests. Patients were also submitted to metabolic staging (MS) with whole-body FDG-PET scan before the beginning of treatment. A standard of reference for staging was determined with all staging procedures, histologic examination, and follow-up examinations. The accuracy of the CCS was compared with the MS. Local unit costs of procedures and tests were evaluated. Incremental cost-effectiveness ratio (ICER) was calculated for both strategies. RESULTS: In the 210 patients with HL, the sensitivity for initial staging of FDG-PET was higher than that of CT and BMB in initial staging (97.9% vs. 87.3%; P < .001 and 94.2% vs. 71.4%, P < 0.003, respectively). The incorporation of FDG-PET in the staging procedure upstaged disease in 50 (24%) patients and downstaged disease in 17 (8%) patients. Changes in treatment would be seen in 32 (15%) patients. Cumulative cost for staging procedures was $3751/patient for CCS compared to $5081 for CCS + PET and $4588 for PET/CT. The ICER of PET/CT strategy was $16,215 per patient with modified treatment. PET/CT costs at the beginning and end of treatment would increase total costs of HL staging and first-line treatment by only 2%. CONCLUSION: FDG-PET is more accurate than CT and BMB in HL staging. Given observed probabilities, FDG-PET is highly cost-effective in the public health care program in Brazil.

18F-FDG PET after 2 cycles of ABVD predicts event-free survival in early and advanced Hodgkin lymphoma.

UNLABELLED: Our objective was to assess the prognostic value of (18)F-FDG PET after 2 cycles of chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma (HL) patients overall and in subgroups of patients with early and advanced stages and with low and high risks according to the International Prognostic Score (IPS). METHODS: One hundred fifteen patients with newly diagnosed HL were prospectively included in the study. All underwent standard ABVD therapy followed by consolidation radiotherapy in cases of bulky disease. After 2 cycles of ABVD, the patients were evaluated with PET (PET2). Prognostic analysis compared the 3-y event-free survival (EFS) rate to the PET2 results, clinical data, and IPS. RESULTS: Of the 104 evaluated patients, 93 achieved complete remission after first-line therapy. During a median follow-up of 36 mo, relapse or disease progression was seen in 22 patients. Treatment failure was seen in 16 of the 30 PET2-positive patients and in only 6 of the 74 PET2-negative patients. PET2 was the only significant prognostic factor. The 3-y EFS was 53.4% for PET2-positive patients and 90.5% for PET2-negative ones (P < 0.001). When patients were categorized according to low or high IPS risk and according to early or advanced stage of disease, PET2 was also significantly associated with treatment outcome. CONCLUSION: PET2 is an accurate and independent predictor of EFS in HL. A negative interim (18)F-FDG PET result is highly predictive of treatment success in overall HL patients, as well as in subgroups with early or advanced-stage disease and with low or high IPS risk.

Cost effectiveness of positron emission tomography in patients with Hodgkin's lymphoma in unconfirmed complete remission or partial remission after first-line therapy.

PURPOSE: To assess the cost effectiveness of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with Hodgkin's lymphoma (HL) with unconfirmed complete remission (CRu) or partial remission (PR) after first-line treatment. PATIENTS AND METHODS: One hundred thirty patients with HL were prospectively studied. After treatment, all patients with CRu/PR were evaluated with FDG-PET. In addition, PET-negative patients were evaluated with standard follow-up, and PET-positive patients were evaluated with biopsies of the positive lesions. Local unit costs of procedures and tests were evaluated. Cost effectiveness was determined by evaluating projected annual economic impact of strategies without and with FDG-PET on HL management. RESULTS: After treatment, CRu/PR was observed in 50 (40.0%) of the 127 patients; the sensitivity, specificity, and positive and negative predictive values of FDG-PET were 100%, 92.0%, 92.3%, and 100%, respectively (accuracy of 95.9%). Local restaging costs without PET were $350,050 compared with $283,262 with PET, a 19% decrease. The incremental cost-effectiveness ratio is -$3,268 to detect one true case. PET costs represented 1% of total costs of HL treatment. Simulated costs in the 974 patients registered in the 2008 Brazilian public health care database showed that the strategy including restaging PET would have a total program cost of $56,498,314, which is $516,942 less than without restaging PET, resulting in a 1% cost saving. CONCLUSION: FDG-PET demonstrated 95.9% accuracy in restaging for patients with HL with CRu/PR after first-line therapy. Given the observed probabilities, FDG-PET is highly cost effective and would reduce costs for the public health care program in Brazil.

Myocardial blood flow assessment with 82rubidium-PET imaging in patients with left bundle branch block

OBJECTIVES: Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease. OBJECTIVE: We sought to investigate rubidium-82 (82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block. METHODS: Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress 82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII). RESULTS: Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001). CONCLUSION: The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by 82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.

Association between major depressive symptoms in heart failure and impaired regional cerebral blood flow in the medial temporal region: a study using 99m Tc-HMPAO single photon emission computerized tomography (SPECT).

BACKGROUND AND PURPOSE: Depressive symptoms are frequently associated with heart failure (HF), but the brain mechanisms underlying such association are unclear. We hypothesized that the presence of major depressive disorder (MDD) emerging after the onset of HF would be associated with regional cerebral blood flow (rCBF) abnormalities in medial temporal regions previously implicated in primary MDD, namely the hippocampus and parahippocampal gyrus. METHOD: Using 99mTc-SPECT, we measured rCBF in 17 elderly MDD-HF patients, 17 non-depressed HF patients, and 18 healthy controls, matched for demographic variables. Group differences were investigated with Statistical Parametric Mapping. RESULTS: Significant rCBF reductions in MDD-HF patients relative to both non-depressed HF patients and healthy controls were detected in the left anterior parahippocampal gyrus and hippocampus (ANOVA, p=0.008 corrected for multiple comparisons) and the right posterior hippocampus and parahippocampal gyrus (p=0.005 corrected). In the overall HF group, there was a negative correlation between the severity of depressive symptoms and rCBF in the right posterior hippocampal/parahippocampal region (p=0.045 corrected). CONCLUSIONS: These findings are consistent with the notion that the medial temporal region is vulnerable to brain perfusion deficits associated with HF, and provide evidence that such functional deficits may be specifically implicated in the pathophysiology of MDD associated with HF.

Myocardial perfusion scintigraphy to predict outcomes after coronary stenting.

The value of myocardial perfusion scintigraphy (MPS) in predicting the occurrence of restenosis or new coronary lesions after stent implantation is debatable. A total of 47 patients treated with successful bare stent implantation underwent stress gated SPECT MPS at three time-points: pre-procedure, early pos-procedure, and 6-month follow-up. Follow-up angiographic re-study was obtained at 6 months. Overall, 51.1% of patients had angiographic in-stent restenosis or a new lesion at follow-up. Pre-procedure MPS and early MPS scans did not differ between patients with or without restenosis/new lesions. At follow-up transient perfusion defects were observed in 26.1% of patients without restenosis/new lesions and in 75.0% of patients presenting with restenosis/new lesions (p<0.01) (sensitivity: 75.0%; especificity: 73.9%). When comparing early post procedure MPS to follow-up MPS, patients without restenosis/new lesions had no changes or a decrease in the number of segments with transient defects (median difference 0 [interquartile range -2 - 0]), while patients with restenosis/new lesions had an increase in transient defects (+2 [interquartile range 2 - 3.75]; p<0.01). Two multivariate factors independently predicted new lesion/restenosis: reference diameter < 2.9 mm (OR 6.50; p=0.05) and the difference in the number of segments with transient defects between early post procedure and follow-up MPS (OR 1.87; p<0.01). In conclusion, pre-procedure and early MPS did not predict complications after coronary stenting, while follow-up MPS was suboptimal in differentiating patients with or without new lesions/restenosis. However, the change in myocardial perfusion from early post-procedure to the follow-up scan was an important -prognostic factor to predict the incidence of new lesion/restenosis.

Myocardial delayed enhancement by magnetic resonance imaging in patients with Chagas' disease: a marker of disease severity.

OBJECTIVES: We sought to investigate whether myocardial delayed enhancement (MDE) by magnetic resonance imaging (MRI) could quantify myocardial fibrosis (MF) in patients with Chagas' heart disease (CHD), thus defining the severity of the disease. BACKGROUND: Myocardial fibrosis secondary to ischemic disease can be imaged using MDE. Advanced CHD is characterized by progressive MF. METHODS: Fifty-one patients with CHD were enrolled: 15 seropositive asymptomatic participants in the indeterminate phase (IND); 26 patients with known clinical CHD; and 10 patients with known CHD and ventricular tachycardia (VT). Using a 1.5-T MRI system, we acquired left ventricular (LV) short-axis slices using cine-MRI (LV function) and inversion-recovery gradient-echo (MDE). RESULTS: Myocardial fibrosis by MRI was present in 68.6% of all patients, in 20% of IND, 84.6% of CHD, and 100% of VT (p < 0.001). Quantified MF increased progressively across disease severity subgroups (0.9 +/- 2.3% in IND; 16.0 +/- 12.3% in CHD; and 25.4 +/- 9.8% in VT, p < 0.001) and New York Heart Association functional classes (I: 7.5 +/- 9.5%; II: 21.9 +/- 13.8%; and III: 25.3 +/- 9.9% of LV mass, p < 0.001). Left ventricular ejection fraction and MF had significant negative correlation (r = -0.78, p < 0.001), similar to the segmental MF and function: 4.9 +/- 15.1% of MF in normal function, 32.5 +/- 32.5% in mildly hypokinetic, 57.8 +/- 31.4% in severely hypokinetic, and 72.3 +/- 36.2% in akinetic and dyskinetic segments, respectively (p < 0.001). CONCLUSIONS: In CHD, MDE by MRI quantifies MF that not only can be detected in the early asymptomatic stages but parallels well-established prognostic factors and provides unique information for clinical disease staging.

Detecçäo do miocárdio viável: estudo de perfusäo, antes e após a cirurgia de revascularizaçäo em portadores de infarto do miocárdio / Detection of the viable myocardium: a perfusion scintigraphic study, before and after coronary bypass surgery in myocardial infarction patients

Objective - To compare single-photon-emission computed tomography (SPECT) imaging scans using (201)Tl and (99m)Tc-MIBI in detection of viable myocardium, in regions compromised by infraction. Methods - Thirty-two (59.3+9.8 years old and 87 per cent male) myocardial infarction patients were studied. All had Q waves on the ECG and left ventricle ejection fraction of <50 per cent. They underwent coronary and left ventricle angiographies and SPECT before (including (201)Tl reinjection) and after coronary artery bypass surgery (CABG). Improvement in perfusion observed after surgery was considered the gold standard for myocardial viability. Results - Among 102 studied regions of the heart, there were 40 (39.2 per cent) areas of transient perfusion defects in the conventional protocol with (201)Tl and 52 (51.0 per cent) after reinjection. Therefore, 12/62 (19.4 per cent) more viable regions were identified by reinjection. Using (99m)Tc-MIBI, only 14 (13.7 per cent) regions with transient defects were identified, all of which were seen also in (201)Tl protocols. After surgery, 49 of total of 93 regions analyzed (52.7 per cent) were viable. Sensitivity, specificity, accuracy, positive and negative prediction values were, respectively, (201)Tl SPECT scans-65.3 per cent, 90.9 per cent, 77.4 per cent, 88.9 per cent and 70.2 per cent, reinjection protocol with (201)Tl scans - 81.6 per cent, 81.8 per cent, 81.7 per cent, 83.3 per cent and 80.0 per cent; (99m)Tc-MIBI SPECT scans - 20.4 per cent, 90.9 per cent, 53.8 per cent, 71.4 per cent and 50.6 per cent. Logistic regression demonstrated that the reinjection protocol with (201)Tl was the best predictor of viability (P<0.001). Conclusion - Our data suggest the election of (201)Tl for viability studies, especially when using the reinjection protocol.

Estratégia para individualizar uma dose eficiente de betabloqueador em pacientes idosos com isquemia miocárdica e função ventricular esquerda preservada / Strategy for identifying an efficient dosage of beta-blocker for elderly patients with myocardial ischemia and preserved left ventricular function

OBJETIVO: Avaliar estratégia de titulação para prescrever uma dose de propranolol que seria eficiente em reduzir isquemia do miocárdio em idosos. MÉTODOS: Foram estudados 14 homens idosos (73,6 ± 5,3 anos), portadores de doença coronariana estável, documentada pela cinecoronariografia, com resposta isquêmica ao teste ergométrico e função ventricular esquerda preservada. O propranolol foi titulado a fim de atingir redução de 15 por cento na freqüência cardíaca, ao final da carga de 50 W (correspondente às atividades diárias normais de idosos), em testes ergométricos semanais e feito estudo cintilográfico sincronizado das câmaras cardíacas, em repouso e durante exercício, antes e após seu uso. RESULTADOS: As reduções da freqüência cardíaca na carga de 50 W e em repouso foram semelhantes (21 por cento vs 20 por cento; p=0,5100). O propranolol melhorou a duração do exercício (12,2 ± 2,0 min vs 13,1 ± 1,8 min; p=0,0313) e aboliu as alterações do segmento ST induzidas pelo exercício em 8 (57 por cento) pacientes. Em repouso, a fração de ejeção não foi modificada pelo betabloqueador. Durante o exercício máximo, o propranolol reduziu o índice de volume sistólico final e aumentou a fração de ejeção. CONCLUSAO: A estratégia de empregar betabloqueadores para reduzir a freqüência cardíaca em 15 por cento na carga de 50 W é segura e benéfica nos idosos com isquemia miocárdica e função ventricular preservada. A dose utilizada reduziu a isquemia miocárdica e melhorou a tolerância ao exercício, sem prejudicar o desempenho ventricular durante exercício máximo.

Resultados da cardiomioplastia no tratamento da cardiomiopatia dilatada / Results of cardiomyopathy in the treatment of dilated cardiomyopathy

A cardiomioplastia tem sido proposta como uma alternativa ao transplante cardíaco no tratamento das cardiomiopatias isquêmicas ou dilatadas. No período de maio de 1988 a outubro de 1990, 16 pacientes portadores de cardiomiopatia dilatada foram submetidos à cardiomioplastia no Instituto do Coraçao. Dez pacientes estavam em classe funcional III e seis em classe IV. Nao houve óbitos no período de pós-operatório imediato. O tempo médio de seguimento foi de 16,9 + 2,5 meses e a sobrevida atuarial foi 74 por cento no 1( ano e 64,8 por cento no 2( ano após a cardiomioplastia, sendo influenciada pela má evoluçao dos pacientes operados com diâmetro de ventrículo esquerdo maior do que 80 mm. Esses valores foram superiores, contudo, à sobrevida de um e dois anos de 39,5 e 29,6 por cento, respectivamente, apresentada pelo grupo controle de 20 pacientes mantidos clinicamente (p = O,06). Cinco dos ll pacientes em seguimento após a cardiomioplastia, retornaram à classe funcional I e seis estao em classe II. Aos seis meses de pós-operatório, foi documentada a elevaçao da fraçao de ejeçao do ventrículo esquerdo de 20,1 + 3,8 para 26 + 7,8 por cento pelo estudo radioisotópico (p < O,01), sendo que esse parâmetro se alterou principalmente em pacientes com menor dilataçao da câmara ventricular esquerda. A Doppler-ecocardiografia mostrou que o encurtamento segmentar do ventrículo esquerdo se elevou de 12 ñ 3,1 para 17,8 ñ 2,3 por cento (p < O,01), enquanto que o volume sistólico aumentou de 23,6 ñ 5,2 para 32,3 ñ 7,9 ml (p < O,01). Elevaçoes semelhantes do índice sistóiico, associados à queda da pressao em território pulmonar, foram também observadas pelo cateterismo cardíaco. O estudo ergoespirométrico documentou o aumento do consumo máximo de oxigênio de 14,9 ñ 3,9 para 18,2 ñ 3,4 ml/kg/min (p < O,O5). Um ano e aos 18 meses após a operaçao, as alteraçoes decorrentes da cardiomioplastia permaneceram essencialmente as mesmas. Em conclusao, a cardiomioplastia melhora a funçao ventricular esquerda, reverte o quadro congestivo e melhora a sobrevida de pacientes portadores de cardiomiopatia dilatada. Fatores como a existência de grande cardiomegalia podem, contudo, influenciar a evoluçao tardia dos pacientes submetidos a este procedimento.

Evoluçäo clínica e comportamento da funçäo ventricular no pós-operatório tardio da cardiomioplastia / Clinical evaluation and ventricular function behavior in the late postoperative period of cardiomyoplasty

A cardiomioplastia tem sido proposta, como uma alternativa ao transplante cardíaco, no tratamento de pacientes com insuficiência miocárdica em fase avançada. O objetivo deste trabalho é estudar a evoluçao clínica e o comportamento da funçao ventricular no pós-operatório tardio desse procedimento em 34 pacientes portadores de cardiomiopatia dilatada, que foram operados no período de maio de 1988 a setembro de 1994. Vinte e sete pacientes estavam em classe funcional III e 7 pacientes em classe IV no pré-operatório, apesar do uso de terapêutica clínica otimizada. A mortalidade hospitalar foi de 2,9 por cento e l paciente que evoluiu em choque cardiogênico foi submetido a transplante cardíaco 42 dias após a cardiomioplastia. O tempo de seguimento pós-operatório variou entre 2 e 73 meses, com média de 27,4 meses. Aos 6 meses de pós-operatório, 12 pacientes estavam em classe funcional I, l5 pacientes em classe II e 3 pacientes em classe III (p=O,OOl) em relaçao ao pré-operatório. Quatorze pacientes faleceram até 5 anos de pós-operatório e os índices de sobrevida foram 84,7 por cento em l ano, 67,7 por cento em 2 anos e 39,6 por cento aos 5 anos de seguimento, sendo que, em 9 pacientes, os óbitos ocorreram por progressao da insuficiência cardíaca, e 5 pacientes faleceram subitamente. A análise de regressao de Cox mostrou que a mortalidade nos pacientes operados em classe funcional IV foi 5,5 vezes maior do que nos pacientes operados em classe III (p=O,OO6), cuja sobrevida foi de 52,7 por cento aos 5 anos de pós-operatório. O estudo sistemático da funçao ventricular através da angiografia com radioisótopos, da ecocardiografia com Doppler e do cateterismo cardíaco direito documentou a melhora da fraçao de ejeçao do ventrículo esquerdo (VE) de 19,8 ñ 3 para 23,9 ñ 7,2 por cento (p