Assuero Giorgetti

Myocardial Blood Flow Response to Pacing Tachycardia and to Dipyridamole Infusion in Patients With Dilated Cardiomyopathy Without Overt Heart Failure A Quantitative Assessment by Positron Emission Tomography

BACKGROUND Myocardial blood flow (MBF) impairment has been documented in advanced dilated cardiomyopathy (DCM) in which hemodynamic factors, secondary to severe ventricular dysfunction, may limit myocardial perfusion. To assess whether MBF impairment in DCM may also be present independent of hemodynamic factors, the present study was designed to quantify myocardial perfusion in patients with mild disease without overt heart failure. METHODS AND RESULTS Absolute regional MBF (milliliters per minute per gram) was measured by positron emission tomography and 13N-ammonia in resting conditions, during pacing-induced tachycardia, and after dipyridamole infusion (0.56 mg/kg over 4 minutes) in 22 DCM patients and in 13 healthy subjects. Patients were in New York Heart Association functional class I-II and showed depressed left ventricular (LV) ejection fraction by radionuclide angiography (35 +/- 8%; range, 21% to 48%), normal coronary angiography, and normal or moderately increased LV end-diastolic pressure (9.2 +/- 5.5 mm Hg; range, 2 to 20 mm Hg). There were no differences in arterial blood pressure, heart rate, and rate-pressure product between patients and control subjects in the three study conditions. Compared with control subjects, DCM patients had lower mean MBF at rest (0.80 +/- 0.25 versus 1.08 +/- 0.20 mL.min-1.g-1, P < .01), during atrial pacing tachycardia (1.21 +/- 0.59 versus 2.03 +/- 0.64 mL.min-1.g-1, P < .01), and after dipyridamole infusion (1.91 +/- 0.76 versus 3.78 +/- 0.86 mL.min-1.g-1, P < .01). LV MBF values were related to baseline LV end-diastolic pressure at rest (r = -.57, P < .01) and during pacing (r = -.67, P < .01) but not after dipyridamole infusion (r = .19, P = .40). Five patients had LV end-diastolic pressure > 12 mm Hg; in 4, myocardial perfusion was severely depressed both at baseline and in response to stress. CONCLUSIONS In patients with DCM without overt heart failure, myocardial perfusion is impaired both at rest and in response to vasodilating stimuli. The abnormalities in vasodilating capability can be present despite normal hemodynamics; progression of the disease is associated with more depressed myocardial perfusion.

Homogeneously Reduced Versus Regionally Impaired Myocardial Blood Flow in Hypertensive Patients: Two Different Patterns of Myocardial Perfusion Associated With Degree of Hypertrophy

OBJECTIVES The aim of this study was to quantitatively measure regional and global myocardial blood flow and coronary reserve in hypertensive patients without coronary artery disease and to assess the correlation with left ventricular mass. BACKGROUND The effect of left ventricular hypertrophy on regional vasodilating coronary capability in arterial hypertension is controversial, and no quantitative method has been applied to assess a possible correlation. METHODS Positron emission tomography was performed in 50 untreated hypertensive patients and 13 normotensive subjects. Blood flow at baseline and after dipyridamole was globally and regionally measured by using nitrogen-13 ammonia; coronary reserve and resistance were calculated. Left ventricular mass was assessed by two-dimensional echocardiography. RESULTS In hypertensive patients, flow at baseline was similar to that of normotensive subjects (p = 0.21), but values were reduced after pharmacologic vasodilation (p < 0.05). This impairment of maximal coronary flow was not correlated with left ventricular mass (p = 0.13). Among hypertensive patients, we identified a group with a homogeneous distribution of perfusion and a group with a heterogeneous flow pattern. Flow was globally reduced in the former group, but it was abnormal only at the site of perfusion defects in the latter. Patients with regional defects showed the highest likelihood of having an increased left ventricular mass. CONCLUSIONS In arterial hypertension, left ventricular mass is not correlated with global myocardial blood flow. Nevertheless, patients with ventricular hypertrophy are likely to show a heterogeneous flow pattern with regional defects and almost normal blood flow in nonaffected regions. In hypertensive patients with a homogeneous perfusion pattern during stress, myocardial blood flow frequently shows a diffuse reduction.

Comparative Effects of Enalapril and Verapamil on Myocardial Blood Flow in Systemic Hypertension

BACKGROUND The comparative effects of calcium channel blockers and ACE inhibitors on myocardial blood flow (MBF) in hypertensive patients after long-term treatment are still unknown. METHODS AND RESULTS Twenty hypertensive subjects with normal coronary arteries were randomly assigned to verapamil 240 to 480 mg/d or enalapril 10 to 40 mg/d. MBF was quantified at rest, during pacing tachycardia, and after dipyridamole by positron emission tomography and 13N-ammonia before and 6 months after treatment after 1 week of pharmacological washout. In both groups, blood pressure and heart rate during flow measurements were not different before and after therapy. Before treatment, mean MBF at rest, during pacing tachycardia, and after dipyridamole infusion was similar in the two groups; however, pacing and dipyridamole flows were significantly lower than those obtained in a control group of normotensive subjects. After treatment, in the enalapril-treated patients, MBF did not change in the three study conditions. In the verapamil-treated patients, MBF did not change at rest and significantly increased during pacing and after dipyridamole. The inhomogeneity of regional MBF distribution, evaluated from the coefficient of variation, decreased at rest after both treatments and, in the enalapril group, also during pacing. No relation was found between changes in MBF and changes in left ventricular mass. CONCLUSIONS In arterial hypertension, MBF during pacing tachycardia and after dipyridamole is impaired. Successful therapy with verapamil increases MBF response to these stimuli, independent of changes in perfusion pressure and left ventricular mass. These results suggest that verapamil directly improves coronary microcirculatory function in hypertension. Enalapril does not significantly change MBF but reduces the inhomogeneity of regional flow distribution.

Assessment of anatomic and physiological severity of single-vessel coronary artery lesions by dipyridamole echocardiography. Comparison with positron emission tomography and quantitative arteriography.

BackgroundThe aim of this study was to compare the results of dipyridamole-echocardiography test (DET: twodimensional echo monitoring during dipyridamole infusion up to 0.84 mg/kg over a period of 10 minutes) with both anatomic and physiological parameters of coronary artery disease severity, assessed by computer-assisted quantitative coronary arteriography, and regional coronary flow reserve, measured by [13N]ammonia (13NH3) and dynamic positron emission tomography (PET), respectively. Methods and ResultsWe studied 31 patients with a history of chest pain and neither previous myocardial infarction nor resting wall motion abnormalities. Eighteen patients had single- vessel disease (>50% stenosis of one major coronary vessel), and 13 had normal coronary arteries. The criterion for DET positivity was the appearance of a new transient regional wall motion abnormality. In patients with a positive DET, two parameters were evaluated: the dipyridamole time (ie, the time from the beginning of drug infusion to the development of obvious dyssynergy) and the wall motion score index WMSI, a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of segments interpreted. Quantification of regional myocardial blood flow was obtained by PET measurements of 13NTH3 arterial input function and left ventricular myocardial tissue concentration both at control and after dipyridamole 0.56 mg/kg over 4 minutes). Maximal regional blood flow after dipyridamole in the region supplied by the stenotic vessel was significantly lower in the 11 patients with coronary artery disease and positive DET than in the 7 patients with coronary artery disease and negative DET (1.08±0.33 versus 1.98±0.37 mL ·min−1 · g−1, P < .01). In patients with a positive DET, regional coronary flow reserve correlated well with dipyridamole time (r = .87, P < .01) but not with peak WMSI (r = .25, P = NS). Patients with dipyridamole-induced akinesia or dyskinesia (n=6) had a greater reduction in regional coronary flow reserve than did those showing hypokinesia (n=5): 1.38±0.51 versus 2.17±0.42, P < .05. Percent area reduction was more severe in patients with DET positivity than in those with DET negativity (93.7±8.7% versus 77±10.3%, P < .01), and it correlated with regional coronary flow reserve (r = .64, P < .01) and dipyridamole time (r = − .59, P < .01). ConclusionsIn patients with single-vessel disease, DET shows an excellent specificity but a limited sensitivity; in these patients, DET positivity is associated with a physiologically important coronary stenosis. Severity of the anatomic stenosis and impairment in regional flow reserve are greater when the dipyridamole-induced dyssynergy appears earlier during the test. Therefore, a stratification of the anatomophysiological severity of coronary artery disease can be obtained with DET, based mainly on the temporal allocation of the transient dyssynergy.

Global alteration in perfusion response to increasing oxygen consumption in patients with single-vessel coronary artery disease

BACKGROUND Recent evidence suggests that, in coronary artery disease (CAD), myocardial blood flow (MBF) regulation is abnormal in regions supplied by apparently normal coronary arteries. However, the relation between this alteration and MBF response to increasing metabolic demand has not been fully elucidated. METHODS AND RESULTS MBF was assessed at baseline, during atrial pacing tachycardia, and after dipyridamole (0.56 mg/kg IV over 4 minutes) in 9 normal subjects and in 24 patients with ischemia on effort, no myocardial infarction, and isolated left anterior descending (n = 19) or left circumflex (n = 5) coronary artery stenosis (> or = 50% diameter narrowing). Perfusion of both poststenotic (S) and normally supplied (N) areas was measured off therapy by positron emission tomography and [13N]ammonia. Normal subjects and CAD patients showed similar rate-pressure products at baseline, during pacing, and after dipyridamole. In CAD patients, MBF was lower in S than in N territories at rest (0.68 +/- 0.14 versus 0.74 +/- 0.18 mL.min-1.g-1, respectively, P < .05), during pacing (0.92 +/- 0.29 versus 1.16 +/- 0.40 mL.min-1.g-1, respectively, P < .01), and after dipyridamole (1.18 +/- 0.34 versus 1.77 +/- 0.71 mL.min-1.g-1, respectively, P < .01). However, normal subjects showed significantly higher values of MBF both at rest (0.92 +/- 0.13 mL.min-1.g-1, P < .05 versus both S and N areas), during pacing tachycardia (1.95 +/- 0.64 mL.min-1.g-1, P < .01 versus both S and N areas), and after dipyridamole (3.59 +/- 0.71 mL.min-1.g-1, P < .01 versus both S and N areas). The percent change in flow was strictly correlated with the corresponding change in rate-pressure product in normal subjects (r = .85, P < .01) but not in either S (r = .04, P = NS) or N regions (r = .08, P = NS) of CAD patients. CONCLUSIONS Besides epicardial stenosis, further factors may affect flow response to increasing metabolic demand and coronary reserve in patients with CAD.

A Fast and Effective Method to Assess Myocardial Necrosis by Means of Contrast Magnetic Resonance Imaging

PURPOSE Contrast magnetic resonance (CMR) can identify myocardial necrosis after gadolinium administration as a hyperenhanced (HE) area. Yet there are no software tools that can effectively quantify such an area. The aim of this study is to develop a robust and effective algorithmic method for defining the extent of myocardial necrosis evidenced through CMR. METHOD Fifteen patients with previous myocardial infarction underwent nitrate Tetrofosmin G-SPECT and CMR. A software tool was developed, allowing semiautomatic detection of endocardial and epicardial borders and the automatic detection of HE regions. The accuracy of the proposed quantitative method of analysis has been tested with G-SPECT analysis that it is less than an ideal method for assessing myocardial viability, but at present is accepted and widely used in the clinical arena. RESULTS Segmental (SEHE) and global extension of HE were evaluated. HE was present in 161 of the 255 analyzed segments. Of the 161 HE segments, the mean SEHE was 36 +/- 30%. The operator independence (intraobserver: r = 0.97, p < 0.0001, interobserver: r = 0.95, p < 0.0001) was good and significant, with noticeable time savings with respect to manual analysis. There was strong and inverse correlation between SEHE and scintigraphic regional uptake reduction (r = -0.66, p < 0.0001), and also a positive correlation between SEHE and SPECT defect extension (r = 0.75, p < 0.0001). When assessing the global extent of necrosis, the correlation between the two techniques was strong (r = 0.79, p = 0.0004). CONCLUSIONS The proposed method of quantifying myocardial necrosis by CMR is highly reliable, reproducible, and operator-independent for quantifying.

Alteration in regulation of myocardial blood flow in one-vessel coronary artery disease determined by positron emission tomography

The behavior of myocardial blood flow (MBF) regulation in territories supplied by angiographically normal vessels of patients with coronary artery disease (CAD) has been poorly investigated. Resting MBF and coronary reserve were evaluated in 32 patients with stable angina, no previous myocardial infarction, and isolated left anterior descending or left circumflex coronary artery stenosis (> or = 50% diameter narrowing). MBF was measured, in the absence of any medical therapy, by means of dynamic positron emission tomography and 13N-ammonia. MBF measurements at baseline and after intravenous dipyridamole (0.56 mg/kg administered over 4 minutes), were obtained both in the stenosis-related regions and in contralateral territories. As a control group, 14 normal subjects were evaluated according to the same protocol. At rest, the 32 patients with CAD had similar MBF values in the stenotic and remote regions (0.76 +/- 0.21 and 0.77 +/- 0.19 ml/min/g, respectively, p = NS); both these values were significantly (p < 0.01) reduced with respect to mean MBF in normal subjects (1.03 +/- 0.25 ml/min/g). The dipyridamole study was completed in 30 patients; these patients had lower values of maximal MBF in the stenotic than in the remote regions (1.52 +/- 0.65 vs 1.76 +/- 0.68 ml/min/g, p < 0.05); however, both these values were significantly reduced (p < 0.01) with respect to mean dipyridamole MBF in normal subjects (3.66 +/- 0.92 ml/min/g). Thus, in patients with CAD, resting and maximal MBF can be reduced not only in myocardial territories supplied by stenotic arteries, but also in territories supplied by angiographically normal arteries.

Microvascular dysfunction in collateral-dependent myocardium

OBJECTIVES The aim of this study was to evaluate myocardial blood flow regulation in collateral-dependent myocardium of patients with coronary artery disease. BACKGROUND Despite great clinical relevance, perfusion correlates of collateral circulation in humans have rarely been estimated by quantitative methods at rest and during stress. METHODS Nineteen patients with angina and isolated occlusion of the left anterior descending (n = 14) or left circumflex (n = 5) coronary artery were evaluated. Using positron emission tomography and nitrogen-13 ammonia, we obtained flow measurements at baseline, during atrial pacing-induced tachycardia and after intravenous administration of dipyridamole (0.56 mg/kg body weight over 4 min). Flow values in collateral-dependent and remote areas were compared with values in 13 normal subjects. RESULTS Flow at rest was similar in collateralized and remote myocardium (0.61 +/- 0.11 vs. 0.63 +/- 0.17 ml/min per g, mean +/- 1 SD), and both values were lower than normal (1.00 +/- 0.20 ml/min per g, p < 0.01). During pacing, blood flow increased to 0.83 +/- 0.25 and 1.11 +/- 0.39 ml/min per g in collateral-dependent and remote areas, respectively (p < 0.05 vs. baseline); both values were lower than normal (1.86 +/- 0.61 ml/min per g, p < 0.01). Dipyridamole induced a further increase in perfusion in remote areas (1.36 +/- 0.57 ml/min per g, p < 0.01 vs. pacing) but not in collateral-dependent regions (0.93 +/- 0.37 ml/min per g, p = NS vs. pacing); again, both values were lower (p < 0.01) than normal (3.46 +/- 0.78 ml/min per g). Dipyridamole flow in collateral-dependent myocardium was slightly lower in patients with poorly developed than in those with well developed collateral channels (0.75 +/- 0.29 vs. 1.06 +/- 0.38 ml/min per g, respectively, p = 0.06); however, the former showed higher flow inhomogeneity (collateral/control flow ratio 0.58 +/- 0.10 vs. 0.81 +/- 0.22, respectively, p < 0.02). A linear direct correlation was observed between flow reserve of collateral-dependent and remote regions (r = 0.83, p < 0.01). CONCLUSIONS Despite rest hypoperfusion, collateral-dependent myocardium maintains a vasodilator reserve that is almost fully utilized during increases in oxygen consumption. A global microvascular disorder might hamper adaptation to chronic coronary occlusion.

Comparison Between Ultrafast and Standard Single-Photon Emission CT in Patients With Coronary Artery Disease: A Pilot Study

Background—A novel technology has been developed for ultrafast (UF) single-photon emission CT (SPECT) myocardial perfusion imaging by using a pinhole collimation design and multiple cadmium zinc telluride crystal arrays. The purpose of this study was to compare myocardial perfusion imaging obtained by UF-SPECT with standard (S) SPECT in patients with known or suspected coronary artery disease. Methods and Results—A total of 34 patients underwent single-day 99mTc-tetrofosmin stress/rest myocardial perfusion imaging. UF-SPECT was performed 10 minutes before S-SPECT. Images were qualitatively analyzed, and the summed stress score and summed rest score were calculated. The segmental tracer uptake value (percentage of maximum myocardial uptake) also was quantified for both UF- and S-SPECT. When only 29 of 34 patients with significant coronary lesions were analyzed, the summed stress score was 10.1±4.4 versus 6.4±2.9, respectively, for UF- and S-SPECT (P=0.002). Qualitative and quantitative per-patient analysis showed similar results in detection of coronary artery disease for UF- and S-SPECT. In contrast, per-vessel analysis demonstrated higher regional sensitivity of UF- versus S-SPECT. UF-SPECT showed higher sensitivity in detecting multivessel disease (P=0.003) versus S-SPECT. Conclusions—This pilot study confirms that UF-SPECT provides high-quality fast myocardial perfusion imaging and suggests that it may allow a more-accurate evaluation of both extent and severity of myocardial ischemia in patients with coronary artery disease.

Comparison Between Ultrafast and Standard SPECT in Patients with Coronary Artery Disease: A Pilot Study

Background—A novel technology has been developed for ultrafast (UF) single-photon emission CT (SPECT) myocardial perfusion imaging by using a pinhole collimation design and multiple cadmium zinc telluride crystal arrays. The purpose of this study was to compare myocardial perfusion imaging obtained by UF-SPECT with standard (S) SPECT in patients with known or suspected coronary artery disease. Methods and Results—A total of 34 patients underwent single-day 99mTc-tetrofosmin stress/rest myocardial perfusion imaging. UF-SPECT was performed 10 minutes before S-SPECT. Images were qualitatively analyzed, and the summed stress score and summed rest score were calculated. The segmental tracer uptake value (percentage of maximum myocardial uptake) also was quantified for both UF- and S-SPECT. When only 29 of 34 patients with significant coronary lesions were analyzed, the summed stress score was 10.1±4.4 versus 6.4±2.9, respectively, for UF- and S-SPECT (P=0.002). Qualitative and quantitative per-patient analysis showed similar results in detection of coronary artery disease for UF- and S-SPECT. In contrast, per-vessel analysis demonstrated higher regional sensitivity of UF- versus S-SPECT. UF-SPECT showed higher sensitivity in detecting multivessel disease (P=0.003) versus S-SPECT. Conclusions—This pilot study confirms that UF-SPECT provides high-quality fast myocardial perfusion imaging and suggests that it may allow a more-accurate evaluation of both extent and severity of myocardial ischemia in patients with coronary artery disease.