Search

Background: Myocardial single photon emission computed tomography (SPECT) is an established noninvasive method for the assessment of the functional significance of coronary artery stenoses. Intracoronary pressure measurements to determine fractional flow reserve (FFR) are increasingly performed during coronary angiography whenever an immediate decision regarding possible intervention is required. We hypothesized that the regional summed difference score (SDSr), reflecting reversible perfusion defects in the myocardial supply area of the FFR target vessel, would be the best predictor of an abnormal FFR in patients without prior myocardial infarction. Otherwise, a regional summed stress score (SSSr) should be the best predictor of an abnormal FFR in patients with prior myocardial infarction for different patient subgroups with coronary artery disease., Methods and Results: In this study 50 patients (mean age, 65 +/- 9.1 years; 18 women) with coronary artery disease and a 50% to 75% coronary stenosis (target vessel) were prospectively investigated. Dobutamine myocardial SPECT was performed as a single-day stress/rest protocol by use of technetium 99m sestamibi. For image interpretation, semiquantitative analysis was conducted by calculating SSSr and SDSr. Within 8 (+/-14.9) days, coronary angiography was performed and FFR was calculated by use of a pressure wire (normal FFR, > or = 0.75). The mean FFR of all patients was 0.78 +/- 0.14. Of 50 patients, 17 had an FFR lower than 0.75 in the target vessel. Receiver operating characteristic analysis identified an SDSr of 1 or greater and an SSSr of 3 or greater as the best threshold values for predicting ischemic FFR. Sensitivity, specificity, and negative and positive predictive values of SDSr and SSSr for the detection of FFR values lower than 0.75 in the target vessel were 80%, 76%, 53%, and 92%, respectively, and 70%, 93%, 78%, and 90%, respectively, in patients without prior myocardial infarction and 57%, 50%, 67%, and 40%, respectively, and 100%, 50%, 78%, and 100%, respectively, in patients with prior myocardial infarction. Weak correlation was found between the single values of FFR with both SDSr and SSSr for the different patient subgroups., Conclusion: Among the dobutamine myocardial scintigraphy variables studied, SDSr was the best predictor of an abnormal FFR (cutoff value of 0.75) in patients without prior myocardial infarction. As assumed, SSSr was the best predictor of an abnormal FFR in patients with prior myocardial infarction in the target region.

Unlabelled: Fractional flow reserve (FFR) is a new but well established parameter for the hemodynamic evaluation of coronary stenoses. A FFR below 0.75 was validated as functionally significant in coronary one or two vessel disease. This study was designed to prospectively define the best FFR cut off value (BCV) in patients with multivessel disease using two noninvasive tests, myocardial perfusion scintigraphy (SPECT) and contrast-enhanced dobutamine stress echocardiography (DSE) as reference methods., Methods: 47 symptomatic patients (29 male, mean age 64+/-10 yrs) with angiographically intermediate coronary lesions (50-75% diameter stenosis) entered the study. DSE (5-40 microg/min/kg dobutamine) was performed after intravenous injection of a second generation transpulmonary contrast agent. SPECT (Tc-99m-MIBI) was done at peak stress. All tests (DSE, SPECT and FFR) were performed within 4 weeks., Results: SPECT yielded positive results in 15 and DSE in 16 patients, respectively. Mean FFR measured in the target lesion (RCA n=10; LAD n=22, RCX n=15) was 0.80+/-0.13. FFR was <0.75 in 15 patients. By performing a ROC analysis the BCV (highest sum of sensitivity and specificity) was found at 0.75. At this cut off value using both non-invasive tests as reference method, sensitivity and specificity were 83 and 77%., Conclusion: In patients with multivessel disease, a FFR <0.75 identifies a hemodynamically relevant lesion as compared to DSE and SPECT. This study underlines that FFR criteria are also applicable in patients with complex coronary artery disease.

Background: DSE and SPECT are two well-established methods to non-invasively investigate the functional significance of coronary artery stenoses in patients with coronary artery disease. The measurement of Fractional Flow Reserve has emerged a new invasive reference standard for lesion specific quantification of coronary artery stenoses. The objective of our prospective study was to compare sensitivity and specificity of Dobutamine Stress Echocardiography (DSE) and Single Photon Emission Computer tomography (SPECT) with the pressure derived Fractional Flow Reserve (FFR) for the identification of hemodynamic relevant coronary lesions in patients with predominately coronary multivessel disease and angiographically intermediate stenoses., Methods: Inclusion criteria were a coronary lesion of 50-75% diameter stenosis by visual assessment in patients with known or suspected CAD. SPECT, DSE and FFR testing was performed within one week of coronary angiography., Results: The study comprised 48 consecutive symptomatic patients. In 41 cases, a coronary multivessel disease was present. Mean FFR was 0.80 +/- 0.13 (0.41-1.0). Overall sensitivity of DSE and SPECT was 67% and 69% whereas specificity reached 77% and 87%. However, sensitivity was significantly reduced if the target lesion was located distally. DSE showed poor results if the lesions were located in the circumflex artery or if a history of prior myocardial infarctions was present., Conclusion: DSE and SPECT are both useful methods for the non-invasive assessment of coronary artery disease. DSE showed reasonable combination of sensitivity and specificity even in patients with multivessel disease. Although use of noninvasive stress tests is only limited in patients with prior myocardial infarctions and invasive stress testing should be preferred in these patients.

Background: Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. Therefore, achievement of maximal vasodilatation of the coronary microcirculation is a prerequisite for the measurement of FFR. The study was designed to address the hypothesis that intracoronary adenosine yields more complete vasodilatation of the coronary microcirculation when high doses are used, resulting in a more accurate FFR measurement., Methods: Thirty-six patients with 43 moderate lesions underwent determination of FFR during cardiac catheterization. FFR was calculated in all lesions as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (16, 24, 32 and 40 microg for both coronary arteries) were administered in a randomized fashion., Results: No adverse events occurred with any intracoronary adenosine bolus. At baseline there were no significant differences for mean aortic and distal coronary pressure, heart rate as well as FFR values between the different doses. FFR was not significantly altered from the different incremental adenosine doses. However, in 27 (63%) out of 43 lesions there was a further reduction of FFR up to 0.23 when a dose >16 microg was injected., Conclusions: This study suggests that doses of adenosine up to 40 microg are safe and can be used to achieve a more pronounced vasodilatation in individual patients compared to the standard doses. This may have therapeutic impact with FFR values near cut-off points in patients undergoing diagnostic coronary angiography as well as in patients in whom FFR is used to assess the outcome of interventions.

Fractional flow reserve (FFR) as a new technique for physiological assessment of coronary stenoses could identify patients with CAD in whom the deferral of an intended PCI was more beneficial than performing the planned procedure. It is up to now unknown whether a FFR-based therapy stratification is also safe in patients with multivessel disease and complex coronary lesions. This study demonstrates in 71 symptomatic patients with predominantly multivessel disease and angiographically intermediate coronary lesions that patients do not benefit from PCI procedures in terms of overall survival, target vessel patency or clinical symptoms during 12 month follow-up if FFR is above 0.75.

Objectives: Determination of fractional flow reserve (FFR) allows the functional assessment of coronary stenoses before and after an intervention. Preliminary data suggest that a FFR > or = 0.94 is associated with an excellent clinical outcome after stent implantation. However, these results were limited both by the number of patients included and the use of non-contemporary stent designs. We sought to determine the prognostic value of FFR measurements in a large patient cohort undergoing coronary stent implantation., Methods: Eighty-nine consecutive patients were enrolled in whom a stent implantation was performed and a pressure wire was used as a guide wire. Patients were followed for at least 6 months. Death, myocardial infarction (MI) and target vessel revascularization (TVR) were considered cardiac events. A FFR > or = 0.94 was regarded as an optimal functional result., Results: A complete follow-up was available in all patents. Pre-interventional FFR increased from 0.66 +/- 0.16 to 0.95 +/- 0.05 (p < 0.0001) after stent implantation. Sixteen (18%) events occurred during follow-up including 10 (11.2%) TVR. Final FFR was significantly higher in patients without compared to patients with an event (0.92 +/- 0.06 vs. 0.96 +/- 0.05, p < 0.003). By univariate analysis, the presence of diabetes mellitus, left ventricular function, residual diameter stenosis and final FFR were associated with a worse clinical outcome. In the multivariate analysis, only the final FFR and left ventricular function remained as significant predictors for cardiac events (relative risk, 3.50; 95% CI: 1.29-9.52, P < 0.014, and 0.97; 95% CI: 0.93-1.00, p = 0.047)., Conclusion: These results demonstrate in a nonselected patient cohort a strong correlation between FFR values after coronary stenting and subsequent cardiac events. Further studies have to investigate whether outcome after stenting might be improved by guiding the procedure with a pressure guide wire.

Background: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography., Methods: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR., Results: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR., Conclusion: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.

Background: Transplant coronary artery disease is the major factor limiting long-term survival after cardiac transplantation. Both intravascular ultrasound imaging (IVUS) and intracoronary flow studies have been used to assess the morphologic and functional importance of the disease. However, the impact of epicardial intimal thickening, as quantitated by IVUS, on the resistance vessel response to adenosine has not been explored., Methods and Results: Seventy-six coronary arteries without angiographically overt coronary disease (diameter stenosis visually, < or =50%) were studied with both IVUS and intracoronary Doppler in 54 patients 0.5 to 127 months after transplantation. Mean intimal index and mean lumen cross-sectional area (CSA) were determined by IVUS, and the average was obtained for every coronary artery. Coronary flow average peak velocity (APV) was obtained by Doppler before and after administration of 16 microg adenosine to calculate coronary flow velocity reserve (CFVR) and coronary vascular resistance index (CVRI). The hyperemic pressure-flow velocity ratio (hyperemic mean aortic pressure/hyperemic APV) as an index of minimal coronary resistance was further derived. The intimal index (mean, 20.0+/-10%) did not correlate with either CFVR (mean, 2.9+/-0.7, r=.12) or CVRI (mean, 0.33+/-0.1, r=.16). However, a significant correlation between the intimal index and the hyperemic pressure-flow velocity ratio (mean, 1.52+/-0.47 mm Hg/cm/s, r=.74, P<.0001) was found. The hyperemic pressure-flow velocity ratio was not influenced by the presence or absence of left ventricular hypertrophy or a mild acute rejection period (International Society for Heart and Lung Transplantation grades IA and IB)., Conclusions: This study shows that in patients without angiographically overt coronary disease, the degree of epicardial intimal thickening as quantified by IVUS did not predict the adenosine vasodilator response, when determined by commonly used parameters such as CFVR and CVRI. The hyperemic pressure-flow velocity ratio best reflected the functional significance of transplant coronary artery disease.

Myocardial contrast echocardiography has the potential for assessing changes in regional myocardial perfusion. We used this method to compare papaverine vasodilator response in 10 patients after orthotopic heart transplantation without acute rejection of left ventricular hypertrophy (HTX) and in 15 patients with angiographically normal coronary arteries (control group). Injections of 2 ml of sonicated iopromid (9 paired injections in HTX and 24 paired injections in the control group) were performed before and after intracoronary application of papaverine (8 or 10 mg) into the left or right coronary artery. From regional time-intensity curves, alpha (variable of curve width), area under the curve (area), peak contrast intensity (Imax) and contrast decay half-time (T1/2) were derived by from a gamma variate function. T1/2 increased from 4.2 +/- 1.2 to 7.2 +/- 4.0 s (p < 0.01) after papaverine in HTX compared to a change from 4.8 +/- 1.0 to 6.0 +/- 1.7 s (p < 0.001) in normal subjects. Alpha decreased in HTX from 0.44 +/- 0.15 to 0.27 +/- 0.10 s-1 (p < 0.01) after intracoronary papaverine injection. In the control group alpha was 0.37 +/- 0.08 s-1 at rest compared to 0.30 +/- 0.08 s-1 at hyperemic conditions (p < 0.002). Area increased in HTX from 444 +/- 261 to 910 +/- 732 U.s (p < 0.01) and in normal subjects from 352 +/- 171 to 585 +/- 262 U.s (p < 0.001). Hyperemic to baseline flow ratios for area varied from 0.9 to 3.8 (mean 2.17 +/- 1.11) in HTX compared to 1.76 +/- 0.52 (1.03 to 2.71) in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to determine whether changes in myocardial perfusion can be assessed by myocardial contrast echocardiography, intracoronary injections of 2 ml of sonicated iopromid were performed before and 30 to 45 s after application of papaverine in 31 patients (mean age 58 years). 13 patients showed coronary artery disease (KHE), 6 patients hypertensive heart disease (HHE), and 12 patients had no proven heart disease (KTR). Contrast decay-halftime (T/2), maximal video-intensity (Imax) and area under the curve (Area) were derived by computer-assisted videodensitometry. After papaverine KTR showed a significant increase of T/2 (from 5.1 +/- 1.5 to 6.8 +/- 3.2 s, p < 0.05), of Imax (from 36 +/- 13 to 52 +/- 16 E, p < 0.002) and of Area (from 203 +/- 95 to 379 +/- 188 E*s, p < 0.002) compared to baseline values. In this group the ratios of hyperemia to baseline flow conditions were 1.5 +/- 0.4 (from 1.0 to 2.4) for Imax and 1.9 +/- 0.9 (from 1.1 to 3.9) for Area. In HHE and KHE, hyperemia induced no significant changes of T/2, Imax and Area. Heart rate was increased by 4.3% and mean aortic pressure was decreased by 6.2% in all groups after papaverine. Double-product was not altered significantly in any group. Myocardial contrast echocardiography revealed a significant increase in variables of contrast wash-out curves only in patients without proven heart disease. In contrast, no relevant changes of T/2, Imax and Area on average were observed in patients with coronary and hypertensive heart disease. Thus, myocardial contrast echocardiography seems to be suitable to document a reduced papaverine vasodilator response in these patients.

Experimental and clinical studies were performed to assess the ability of myocardial contrast echocardiography for quantitation of regional myocardial blood flow. To evaluate whether myocardial contrast echocardiography is a reproducible technique in humans, 18 nonselected patients undergoing coronary angiography were studied. A total of 107 intracoronary injections into either the left or the right coronary artery were analyzed by computer assisted videodensitometry for peak intensity, contrast decay half-time, and area under the curve. By means of these parameters intraobserver, interobserver, and interinjection variability were determined. Intraobserver measurements showed lowest variability with correlation coefficients of 0.83 for contrast decay half-time, 0.93 for peak intensity, and 0.95 for area under the curve. Mean percent error varied between 6.8% (peak intensity) and 11.2% (area under the curve). The correlation coefficients for interobserver variability ranged from 0.73 for area under the curve to 0.97 for peak intensity. Mean percent error revealed a range between 7.5% for peak intensity and 19% for area under the curve. For interinjection variability, the correlation coefficient for contrast decay half-time was lower (0.56) than for peak intensity (0.73) and area under the curve (0.84). Mean percent error were higher than for intraobserver and interobserver variability (range 24.1% to 34.2%). Thus, intraobserver and interobserver variability for parameters derived from time-intensity curves after intracoronary injection of echo contrast agent in humans are sufficient and comparable to data from animal studies. Interinjection variability, however, showed a higher mean percent error.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to minimize the rate of inadequate myocardial revascularizations, an intraoperative evaluation of regional myocardial perfusion could have practical impact. Current bypass flow measurements have inherent limitations and can determine only epicardial blood flow. To analyze regional graft-dependent myocardial blood flow an echocardiographic short-axis view of the left ventricle was performed intraoperatively in 11 patients undergoing elective coronary artery bypass surgery. After injection of 2 ml of sonicated lopromid (Ultravist 370) into 14 vein grafts, contrast enhancement in the corresponding myocardial regions was clearly visible, no side-effects occurred. Contrast decay halftimes (T/2) were determined by computer-assisted videodensitometry and compared to electromagnetic flow (EMF) rates, which were measured immediately before. T/2 ranged from 2.1 to 6.9 (mean 4.1 +/- 1.5) s and did not correlate to the EMF-rates of 55 to 100 (mean 80 +/- 16) ml/min. Thus intraoperative myocardial echocardiography is a safe and feasible method which allows on-line visualization and off-line quantitation of regional myocardial perfusion intraoperatively.

The intraoperative determination of the success of surgical myocardial revascularization remains problematic because of major limitations in all currently used methods. To assess the regional blood flow of the bypass graft-dependent myocardial segments, 2 ml of sonicated iopromid (a nonionic x-ray contrast medium) was injected into the bypass graft in the beating heart. Simultaneously electromagnetic flow measurements were performed. Eleven graft injections in 8 men (mean age +/- standard deviation 60 +/- 4 years) were performed without any adverse effects. Excellent 2-dimensional cross-sectional views of the left ventricle were obtained in all cases. Ten of 11 injections resulted in adequate myocardial opacification. Computer-assisted evaluation by videodensitometry resulted in time-intensity curves with contrast decay half-times (T1/2) from 2.2 to 6.9 seconds (mean 4.3 +/- 1.4). The corresponding electromagnetic flow ranged from 55 to 100 ml/min (mean 80.0 +/- 16.2). there was no correlation between contrast 2-dimensional echocardiography-derived T1/2 and electromagnetic flow (r = 0.32; p = 0.38). Thus, myocardial contrast echocardiography is a feasible and safe method for intraoperative evaluation of the success of bypass graft surgery. It offers online visualization of perfusion of revascularized myocardium and may allow immediate intraoperative revision of unsuccessful bypass graft placement.

In the treatment of myocardial ischemia in hypertensive patients, nitrates as the basic compound have to be combined with another substance in order to achieve a maximum effect and a 24-h-protection. As these patients often show an impaired left ventricular function because of arterial hypertension or previous myocardial infarction, a further deterioration of the left ventricular ejection fraction (EF) has to be avoided. We therefore investigated in a pilot study. EF, blood pressure, and ST-segment depression under isosorbide dinitrate 120 mg s.r. alone, and in combination with verapamil 120 mg s.r. in 14 male patients with angiographically proven coronary artery disease and arterial hypertension. EF at rest ranged from 29% to 76%. Radionuclide ventriculography was performed at rest and simultaneously with the ECG during exercise before medication, 2 h after ISDN and 4 h after the additional intake of verapamil. The systolic blood pressure at rest fell from 159 +/- 14 to 132 +/- 10 (p less than 0.001) after 2 h and to 132 +/- 16 mmHg after 6 h (p less than 0.01). During exercise there was a decrease from 196 +/- 21 to 174 +/- 21 (p less than 0.01) and to 178 +/- 22 mmHg (p less than 0.001), respectively. The ST-segment depression was reduced from 2.2 +/- 1.1 to 0.8 +/- 0.6 (p less than 0.01) and to 0.9 +/- 0.5 mm (p less than 0.001). EF at rest improved from 53 +/- 14% to 57 +/- 14% after ISDN alone and to 58 +/- 15% after ISDN + verapamil (p less than 0.01), and during exercise from 57 +/- 20% to 62 +/- 19% (p less than 0.05) and to 61 +/- 17% (n.s.). Even in the subgroup of patients with impaired LV-EF (8 at rest and 7 pts during exercise) there was a significant improvement (p less than 0.05) as well after ISDN alone, as there was with combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)