Douglas S. Schulman

Correlations between coronary flow reserve measured with a Doppler guide wire and treadmill exercise testing

We compared exercise test results to a physiologic depiction of stenosis severity, coronary flow reserve (CFR), measured with a Doppler guide wire in 35 patients with single-vessel coronary disease. Group 1 (n = 21) had abnormal CFR, and group 2 (n = 14) had normal CFR. In group 1, 14 of 21 had ST-segment depression versus 3 of 14 in group 2 (p < 0.01). Exercise treadmill time (Bruce protocol) was normalized to the age- and sex-predicted time. Exercise time and normalized exercise time were less in group 1 (5.6 +/- 2.3 vs 9.9 +/- 1.8 min and 0.82 +/- 0.32 vs 1.25 +/- 0.23, p < 0.00001). Having either ST-segment depression or a normalized exercise time <1 during exercise had a 95% sensitivity, 71% specificity, and 86% predictive accuracy in identifying abnormal CFR. Coronary stenoses and minimal lumen diameter were similar in groups 1 and 2. By using stepwise logistical regression analysis, exercise time and ST-segment depression predicted CFR with a total r2 of 0.51. Minimal lumen diameter did not significantly add to the model. Exercise test variables, ST-segment depression, and exercise time are predictive of the physiologic significance of coronary lesions.

Mild mitral insufficiency is a marker of impaired left ventricular performance in aortic stenosis

Whether mitral insufficiency is a marker of decreased left ventricular function in patients undergoing aortic valve replacement for sever aortic stenosis was examined. Hemodynamic measurements in 26 patients with pure aortic stenosis (Group 1), 17 patients with aortic stenosis and grade 1 or 2 mitral insufficiency (Group 2) and 19 control patients were compared. All patients were free of significant coronary artery disease. Ventriculograms were digitized for calculation of ejection fraction, ventricular volumes and wall stress. Despite similar aortic valve areas, Group 2 patients had more advanced symptoms. Cardiac index was comparably decreased in Group 1 (2.6 +/- 0.4 liters/min per m2) and Group 2 (2.7 +/- 0.8 liters/min per m2) compared with the control group (3.8 +/- 0.6 liters/min per m2). Left ventricular end-diastolic and end-systolic volume indexes were increased only in Group 2 (119 +/- 35 and 73 +/- 36 ml/m2, respectively). Likewise, end-systolic wall stress was increased only in Group 2 (149 +/- 54 kdynes/cm2). Ejection fraction was decreased to a greater extent in Group 2 (42 +/- 17%) than in Group 1 (59 +/- 13%) as compared with values in the control group (68 +/- 5%). Although an inverse relation existed between ejection fraction and end-systolic stress in all groups, the ejection fraction (extrapolated to end-systolic stress = 0) was decreased in Group 2, and the slope of the relation was increased in Groups 1 and 2. The end-systolic stress/end-systolic volume index ratio, an index of ventricular performance, was also decreased to a greater extent in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical application of coronary flow reserve using an intracoronary Doppler guide wire.

Coronary flow reserve (CFR) is a critical measurement in the assessment of the coronary circulation. The development of this physiologic variable in animal and human studies is reviewed. Human studies documenting the limitations of coronary angiography, especially in the setting of severe diffuse coronary artery disease, are analyzed. Furthermore, the important variables that must be accounted for when CFR is measured are examined. With this background, the application of CFR in a variety of clinical settings and the development and use of the Doppler FloWire for its measurement are discussed.

786-2 Coronary Flow Reserve vs Transleslonal Velocity Gradient by Doppler Guidewire in Assessing Intermediate Coronary Stenoses

Intracoronary Doppler guidewire measures of coronary flow reserve (CFR) and translesional velocity gradients (TVG) have been used to determine the physiologic significance of intermediate coronary lesions (40–70%). In many patients with intermediate stenoses CFR and TVG values are discordant, raising the possibility that CFR is diminished due to microvascular rather than epicardial disease. In 13 patients with an intermediate coronary lesion, we used an intracoronary Doppler guidewire to record baseline coronaryflowvelocity proximal and distal to each lesion, thus defining TVG. Peak hyperemic velocity was then recorded distally after an intracoronary bolus of adenosine to obtain CFR. All patients had decreased CFR (meanxa0=xa01.4xa0±xa00.3; normal ≥2.0) but trivial TVG (meanxa0=xa01.3xa0±xa00.3; normal l1.7). Each patient had a reversible perfusion defect on stress SPECT 201 TI imaging and subsequently underwent PTCA. These patients were asked to return at 6 months for a repeat stress SPECT201 TI test. Two patients had restenosis prior to repeat stress testing. The remaining 11 patients had their baseline and 6 month post-PTCA scans analyzed. Region of Interest201 TI Ouantitation (counts as % of normal) Pre-PTCA Stress 77xa0±xa02.5 Post-PTCA Stress 89xa0±xa03.0 * Delay 93xa0±xa03.0 * Delay 93xa0±xa04.0 P(ANOVA)xa0lxa00.0001 * pxa0lxa00.05 vs Pre-PTCA Stress All 11 patients demonstrated qualitative normalization of SPECT 201 TI scans at 6 month follow-up. Ouantitative polar mapping and region of interest analysis confirmed the improvement in perfusion. Therefore, blunted CFR was related to a physiologically significant intermediate stenosis rather than a microvascular cause. It appears that CFR is a more reliable indicator of lesion significance than TVG.

Effect of Verapamil on Ventricular Function: Studies in Denervated Human Heart

Verapamil has complex influences on ventricular function owing to its direct myocardial effects, vasodilation, and reflex activation of the sympathetic nervous system. To investigate the direct myocardial effects of verapamil in humans independent of reflex sympathetic stimulation, we administered the drug to 13 recent heart transplant recipients with denervated ventricles. Hemodynamics and radionuclide angiograms were recorded at baseline, with altered loading conditions, and after intravenous (i.v.) verapamil (median dose 4 mg). Left ventricular (LV) systolic and diastolic function was analyzed by systolic pressure-volume relations (SPVR) and peak filling rate (PFR), respectively. Verapamil caused a decrease in blood pressure (BP) and heart rate (HR) with increases in right atrial pressure (RAP 6 +/- 3-8 +/- 3, p < 0.01) and pulmonary artery wedge pressure (PAWP, 9 +/- 3-11 +/- 3 mm Hg, p < 0.01) pressures. LV ejection fraction (EF) decreased (69 +/- 7-66 +/- 8%, p < 0.02) in association with an increase in LV end-systolic counts (3.45 +/- 1.27 to 4.72 +/- 1.78 kcts, p < 0.001). In 11 of 13 patients, the SPV point after verapamil administration was decreased from the line established during altered loading conditions. PFR (4.05 +/- 0.81 to 4.11 +/- 0.76 EDV/s) was unchanged. In the denervated ventricle, verapamil has negative chronotropic and inotropic effects with minimal effects on PFR.

1028-67 Coronary Flow Reserve and Stress SPECT 201TI in Intermediate Saphenous Vein Graft Lesions

Coronary flow reserve (CFR) has become a useful means for determining the physiologic significance of native coronary lesions. While CFR normalizes following coronary bypass surgery, the utility of CFR in the evaluation of saphenous vein graft (SVG) lesions has not been defined. Therefore, we examined the correlation between CFR and stress SPECT 201TI results in 13 patients with SVG lesions of intermediate severity (40– 80% stenosis). In each patient, the SVG supplied normal myocardium, and the bypassed vessel was at least half the diameter of the SVG. Coronary flow velocity was recorded at baseline and following adenosine-induced hyperemia using an 0.014′ intracoronary Doppler guidewire. Patients subsequently underwent exercise SPECT 201TI imaging and were classified by stress 2.201TI results as being normal or having a reversible defect. Twelve SVGs without stenoses supplying normal myocardium served as controls. Control SVGs had a CFR of 2.6xa0±xa00.4, (range 2.0–3.6), Normographic 201TI (nxa0=xa07) Reversible 201TI (nxa0=xa06) p value CFR 2.8xa0±xa006 1.5xa0±xa00.4 0.0001 Stenosis (%) 61xa0±xa09 64xa0±xa013 NS MLD(mm) 1.5xa0±xa00.3 1.3xa0±xa00.5 NS MLDxa0=xa0minimal luminal diameter Quantitative angiographic sperity did not distinguish patients with evidence of ischemia by stress SPECT 201TI imaging. CFR, however, was significantly reduced in patients with reversible 2 1TI defects. Using a normal CFR of ≥2.0, the sensitivity, specificity and predictive accuracy of CFR compared to stress 201TI results were 83%, 100% and 92%, respectively. Thus, Doppler guidewire measures of CFR correlate with stress SPECT 201TI results and may be useful in determining the physiologic significance of intermediate SVG lesions.

978-118 Exercise Capacity and Coronary Flow Reserve in Patients with Intermediate Coronary Stenoses

In patients with coronary disease, exercise time is a predictor of disease severity. More severe disease is associated with shorter exercise time due to greater ischemia. In patients with intermediate coronary stenoses, however, it is unclear whether stenosis severity predicts functional effects. Thus, we examined the relationship between exercise time and the angiographic and physiologic significance of 25 intermediate coronary stenoses (40–70%). Using an intracororary Doppler flow wire we measured coronary flow reserve (CFR) as the ratio of adenosine-induced hyperemic coronary flow velocity to resting velocity. Stenosis severity was determined by quantitative angiography. Patients subsequently underwent maximal exercise testing on a Bruce protocol. No patient had left ventricular dysfunction, ischemia in other vascular distributions or other diseases known to limit exercise capacity. Exercise time was normalized for age and gender according to the method of Bruce. Total exercise time ranged from 3.9 to 12.8xa0min while normalized time ranged from 37 to 152% of predicted. CFR ranged from 1.0 to 3.5 (normalxa0≥xa02.0) and was directly related to exercise time (rxa0=xa00.7, pxa0lxa00.0001, SEExa0=xa02.1) and normalized exercise time (rxa0=xa00.7 pxa0lxa00.0001, SEExa0=xa025), Normalized exercise time was 72xa0±xa021% of predicted in patients with an abnormal CFR vs 125xa0±xa023% of predicted in those with normal CFR (pxa0lxa00.0001). There was no relationship between angiographic percent stenosis and exercise time (rxa0=xa0-0.01) or normalized exercise time (rxa0=xa0-0.01). Normalized exercise time was ≥xa0100% of predicted in 9 of 11 patients with a normal CFR, and lxa0100% in 13 of 14 patients with abnormal CFR. The sensitivity, specificity and predictive accuracy of normalized exercise time for CFR were 93%, 82% and 88%, respectively. Thus, in patients with intermediate coronary stenoses and no other exercise limitations, treadmill exercise time is a useful marker of the physiologic severity of disease.