Timothy A. Dewhurst

Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease.

OBJECTIVES This study sought to establish the validity, reproducibility and responsiveness of the Seattle Angina Questionnaire, a 19-item self-administered questionnaire measuring five dimensions of coronary artery disease: physical limitation, anginal stability, anginal frequency, treatment satisfaction and disease perception. BACKGROUND Assessing the functional status of patients is becoming increasingly important in both clinical research and quality assurance programs. No current functional status measure quantifies all of the important domains affected by coronary artery disease. METHODS Cross-sectional or serial administration of the Seattle Angina Questionnaire was carried out in four groups of patients: 70 undergoing exercise treadmill testing, 58 undergoing coronary angioplasty, 160 with initially stable coronary artery disease and an additional 84 with coronary artery disease. Evidence of validity was sought by comparing the questionnaires five scales with the duration of exercise treadmill tests, physician diagnoses, nitroglycerin refills and other validated instruments. Reproducibility and responsiveness were assessed by comparing serial responses over a 3-month interval. RESULTS All five scales correlated significantly with other measures of diagnosis and patient function (r = 0.31 to 0.70, p < or = 0.001). Questionnaire responses of patients with stable coronary artery disease did not change over 3 months. The questionnaire was sensitive to both dramatic clinical change, as seen after successful coronary angioplasty, and to more subtle clinical change, as seen among outpatients with initially stable coronary artery disease. CONCLUSIONS The Seattle Angina Questionnaire is a valid and reliable instrument that measures five clinically important dimensions of health in patients with coronary artery disease. It is sensitive to clinical change and should be a valuable measure of outcome in cardiovascular research.

Selective Uptake of Radiolabeled Annexin V on Acute Porcine Left Atrial Thrombi

BACKGROUND Annexin V is a human phospholipid binding protein that binds to activated platelets in vitro. We sought to determine the potential of this agent for imaging intracardiac thrombi in swine. METHODS AND RESULTS Left atrial thrombi were formed by crush injury. In initial nonimaging experiments using intravenous 125I-labeled human annexin V, the mean thrombus/whole blood ratio was 13.4 +/- 4.8 for the entire thrombus using well counting of resected specimens (n = 8). Using intravenously injected 99mTc-labeled human annexin V, the left atrial thrombus/blood ratio by well counting was similar (14.2 +/- 10.6 for the entire thrombus and 26.2 +/- 14.9 for the peak section) (n = 12). The ratio for a control protein, 125I-ovalbumin, was only 1.0 +/- 0.2. 99mTc tomographic imaging was positive (n = 10) or equivocal (n = 2) in all experiments with but negative in 10 controls without left atrial thrombi. By region-of-interest analysis of the tomographic images, the mean left atrial appendage/blood ratio at 2 hours in animals with a thrombus was 3.90 +/- 1.12 compared with 0.84 +/- 0.10 in closed chest controls and 1.01 +/- 0.23 in open chest controls (P < .001). CONCLUSIONS We conclude that 99mTc-labeled human annexin V detects acute left atrial thrombi in vivo in swine. The combination of a new thrombus detection agent, annexin V, with a 99mTc label may allow in vivo imaging of thrombi in humans.

Evaluation of annexin V as a platelet-directed thrombus targeting agent

Annexin V is a human phospholipid binding protein (M(r) 36,000) that binds with high affinity to activated platelets in vitro. We studied the biodistribution and thrombus binding of annexin V in rabbit and swine models of fully occlusive arterial thrombi formed 1-2 h prior to injection of annexin V. Iodinated annexin V was cleared from blood in a rapid early phase (t1/2 = 6.4 min, 76% of radioactivity) and a slower late phase (t1/2 = 71 min, 24% of radioactivity). Organ uptake was highest in the kidney and spleen and lowest in heart and skeletal muscle. Thrombus/blood uptake ratios were (mean +/- SEM): 6.39 +/- 1.80 for rabbit iliac artery, 6.97 +/- 1.45 for swine carotid artery, and 7.68 +/- 1.70 for swine femoral artery (all p values < 0.01 versus control artery); a control protein, ovalbumin, showed an uptake ratio of 0.59 +/- 0.08 in swine femoral artery thrombi. These results indicate that annexin V is useful as an agent for selective targeting of platelet-containing thrombi.

Influence of Doppler sample volume location on ventricular filling velocities

Abstract The ratio of peak early diastolic (E) and peak late diastolic (A) velocities, measured from the Doppler mitral waveform, has been used widely to assess left ventricular diastolic function. 1–10 This ratio is also affected by age, 2,11 heart rate 12 and loading conditions. 4,6,9 In some studies, Doppler waveforms have been recorded by sampling at the mitral anulus, 1–4 in others the sample volume has been placed between the free margins of the mitral leaflets, 5–7 and in some the measurement site has not been clearly defined. 8–10 There is no consensus regarding the optimal position. In the present study we measured E A ratio at both the mitral tips and anulus in 300 consecutive patients to determine if sample volume location had an important influence.