Gabriel B. Grossman

High Doses of Vascular Endothelial Growth Factor 165 Safely, but Transiently, Improve Myocardial Perfusion in No-Option Ischemic Disease

UNLABELLED Gene therapy can induce angiogenesis in ischemic tissues. The aim of this study was to assess safety, feasibility, and results, both clinical and on myocardial perfusion, of gene therapy in refractory angina. This was a phase I/II, prospective, temporal-controlled series, clinical trial. Thirteen patients were maintained for minimum 6 months under optimized clinical management, and then received intramyocardial injections of 2000 μg plasmid vascular endothelial growth factor 165 and were followed by single-photon emission computed tomography (SPECT), treadmill tests, Minnesota quality of life questionnaire (QOL), and New York Heart Association (NYHA) functional plus Canadian Cardiovascular Society (CCS) angina classifications. There were no deaths, early or late. During the optimized clinical treatment, we observed worsening of rest ischemia scores on SPECT (p<0.05). After treatment, there was a transitory increase in myocardial perfusion at the third-month SPECT under stress (pre-operative [pre-op] 18.38 ± 7.51 vs. 3 months 15.31 ± 7.30; p<0.01) and at the sixth month under rest (pre-op 13.23 ± 7.98 vs. 6 months: 16.92 ± 7.27; p<0.01). One year after, there were improvements in treadmill test steps (pre-op 2.46 ± 2.07 vs.12 months 4.15 ± 2.23; p<0.01) and oxygen consumption (pre-op 7.66 ± 4.47 vs.12 months 10.89 ± 4.65; p<0.05), QOL (pre-op 48.23 ± 18.35 vs.12 months 28.31 ± 18.14; p<0.01) scores, and CCS (pre-op 3 [3-3.5] vs.12 months 2 [1-2.5]; p<0.01) and NYHA (pre-op 3 [3-3] vs. 2 [2-2] vs. 12 months 2 [1-2]; p<0.01) classes. Gene therapy demonstrated to be feasible and safe in this advanced ischemic cardiomyopathy patient sample. There were improvements in clinical evaluation parameters, and a transitory increase in myocardial perfusion detectable by SPECT scintigraphy. CLINICAL TRIAL REGISTRATION NCT00744315 http://clinicaltrials.gov/

Prognostic implications of the difference between left ventricular ejection fractions after stress and at rest in addition to the quantification of myocardial perfusion abnormalities obtained with gated SPECT.

Background The prognostic significance of the difference between poststress and at rest left ventricular ejection fraction (&Dgr;LVEF) in patients sent for diagnostic myocardial perfusion study (MPS) is not well characterized. The purpose of this study was to prospectively evaluate the ability of &Dgr;LVEF in further risk stratifying these patients in addition to the severity/extent of myocardial perfusion abnormalities expressed as the total perfusion deficit at stress (sTPD), according to the type of stress used. Methods and Results Two-day 99mTc-MIBI MPS after stress and rest were obtained for 507 patients subdivided according to the type of stress used, sTPD values, and &Dgr;LVEF. Subsequent cardiac events were determined through a standardized questionnaire applied 1, 2, and 6 years after MPS. Independent of the type of stress used, the 6-year event rate with progressive perfusion and functional abnormalities combined was significant for total events, all-cause death, cardiac death, and revascularization but not for myocardial infarct. When &Dgr;LVEF decreased by more than −10%, only those individuals with sTPD of 5% or less had increased 6-year total event rates [5.9% vs 15% for those submitted to treadmill test (P < 0.001) and 8.3% vs 19% when submitted to pharmacological stress (P = 0.001)]. An sTPD greater than 5% was the only variable predictive of total events when multivariate analysis was applied (P < 0.001 for treadmill exercise and P = 0.033 for dipyridamole). Conclusions Estimation of &Dgr;LVEF in addition to sTPD seems to improve risk stratification for future events when &Dgr;LVEF decreases by more than −10% for those individuals with normal or near-normal myocardial perfusion (sTPD ⩽ 5%). An sTPD greater than 5% was a better prognostic indicator of future events when compared with &Dgr;LVEF for individuals with greater perfusion abnormality at stress.

Pitfalls and Artifacts in Cardiac Imaging

ECG gated myocardial perfusion single photon emission computerized tomographic (SPECT) studies, properly acquired, processed, displayed, quantified, and interpreted, provide important perfusion and function information that has been shown to have high efficacy in the diagnosis, prognosis, and management of patients with coronary artery disease (CAD). Totally automatic computer processing software packages have been developed and validated for assisting physicians in their assessment of myocardial perfusion and function. These programs help to expedite, standardize, and objectify image processing and interpretation.1–3

Correct interpretation of a myocardial perfusion SPECT study in a patient with Ebstein’s anomaly through recognition of septal artifact

ConclusionQuantitative assessment by use of polar maps and normal files increases the confidence of interpretation in most cases.4,5 However, when altered anatomy not accounted for in the normal database is present, the results can be misleading. This case illustrates the necessity for complete review of the patient’s history, rotating planar images, oblique slices, and polar maps to properly interpret a study.