Edward P. Shapiro

Diagnostic Performance of Coronary Angiography by 64-Row CT

BACKGROUND The accuracy of multidetector computed tomographic (CT) angiography involving 64 detectors has not been well established. METHODS We conducted a multicenter study to examine the accuracy of 64-row, 0.5-mm multidetector CT angiography as compared with conventional coronary angiography in patients with suspected coronary artery disease. Nine centers enrolled patients who underwent calcium scoring and multidetector CT angiography before conventional coronary angiography. In 291 patients with calcium scores of 600 or less, segments 1.5 mm or more in diameter were analyzed by means of CT and conventional angiography at independent core laboratories. Stenoses of 50% or more were considered obstructive. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate diagnostic accuracy relative to that of conventional angiography and subsequent revascularization status, whereas disease severity was assessed with the use of the modified Duke Coronary Artery Disease Index. RESULTS A total of 56% of patients had obstructive coronary artery disease. The patient-based diagnostic accuracy of quantitative CT angiography for detecting or ruling out stenoses of 50% or more according to conventional angiography revealed an AUC of 0.93 (95% confidence interval [CI], 0.90 to 0.96), with a sensitivity of 85% (95% CI, 79 to 90), a specificity of 90% (95% CI, 83 to 94), a positive predictive value of 91% (95% CI, 86 to 95), and a negative predictive value of 83% (95% CI, 75 to 89). CT angiography was similar to conventional angiography in its ability to identify patients who subsequently underwent revascularization: the AUC was 0.84 (95% CI, 0.79 to 0.88) for multidetector CT angiography and 0.82 (95% CI, 0.77 to 0.86) for conventional angiography. A per-vessel analysis of 866 vessels yielded an AUC of 0.91 (95% CI, 0.88 to 0.93). Disease severity ascertained by CT and conventional angiography was well correlated (r=0.81; 95% CI, 0.76 to 0.84). Two patients had important reactions to contrast medium after CT angiography. CONCLUSIONS Multidetector CT angiography accurately identifies the presence and severity of obstructive coronary artery disease and subsequent revascularization in symptomatic patients. The negative and positive predictive values indicate that multidetector CT angiography cannot replace conventional coronary angiography at present. (ClinicalTrials.gov number, NCT00738218.)

Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging.

It has been postulated that rotation of the left ventricular apex with respect to the base is a component of normal systolic function in humans, but it has been difficult to measure it noninvasively. Tagging is a new magnetic resonance imaging technique that labels specific areas of myocardium by selective radio-frequency excitation of narrow planes orthogonal to the imaging plane before acquiring an image. Tags appear as black lines and persist in myocardium for 400-500 msec and, if applied at end diastole, will move with the myocardium through systole. Tagging was used to noninvasively quantify left ventricular torsion and circumferential-longitudinal shear (shearCL) in humans. Eight normal volunteers, aged 24-38 years, were imaged in a 0.38-T iron-core resistive magnet. Five short-axis left ventricular images, positioned to encompass the entire left ventricle (LV), were obtained separately at end systole. Four equiangular radial tags had been applied at end diastole, intersecting the myocardium at eight locations. We calculated the difference in angular displacement of each epicardial and endocardial tag point (a tag point being where the tag crossed the epicardium or endocardium) at end systole from the systolic position of the corresponding tag point on the basal plane. This value was called the torsion angle. From this, shearCL, the angle inscribed on the epicardial or endocardial surface between the systolic tag position, the corresponding basal tag position, and its projection onto the slice of interest could be calculated at 32 points in the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)

A Randomized Trial of Intravenous Tissue Plasminogen Activator for Acute Myocardial Infarction with Subsequent Randomization to Elective Coronary Angioplasty

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.

Dissociation between left ventricular untwisting and filling. Accentuation by catecholamines.

Background Efficient early diastolic filling is essential for normal cardiac function. Diastolic suction, as evidenced by a decreasing left ventricular pressure during early filling, could result from restoring forces (the release of potential energy stored during systolic deformation) dependent on myofilament relaxation. Although these restoring forces have been envisioned within individual myofibers, recent studies suggest that gross fiber rearrangement involving the connective tissue network occurs early in diastole. This may lead to the release of potential energy stored during systole and suction-aided filling. Methods and Results To establish precisely the timing and extent of restoration of the systolic torsional deformation of the left ventricle with respect to early filling at baseline and with enhanced relaxation, we studied untwisting during control conditions and with catecholamine stimulation. Using noninvasive and nondestructive magnetic resonance tagging, torsional deformation of the left ventricle was measured at 20-msec intervals in 10 open-chest, atrially paced dogs, starting at aortic valve closure. Eight equiangular tags intersected the epicardium and endocardium in three short-axis imaging planes (base, mid, and apex). From the intersection points, epicardial and endocardial circumferential chord and arc lengths were measured and angular twist of mid and apical levels with respect to the base (maximal torsion and its reversal, untwisting) was calculated. Echo-Doppler provided timing of aortic valve closure and of mitral valve opening. Zero torsion was defined at end diastole. Torsion at the apical level reversed rapidly between its maximum and the time immediately after mitral valve opening: from 7.0±5.80 to 3.2±5.40 and 12.0±8.50 to 6.9±7.80 (mean±SD, both p < 0.01) at the epicardium and endocardium, respectively. During the same period, no significant circumferential segment length changes occurred. As expected, after mitral valve opening, filling resulted in significant circumferential segment lengthening, whereas further reversal of torsion was small and nonsignificant. During dobutamine infusion, torsion at end systole was greater and reversal during isovolumic relaxation was much more rapid and greater in extent (p < 0.01). Torsion reversed from 11.5±4.3° to 5.7±4.8° and 17.4±6.4° to 6.9±7.7° at epicardium and endocardium. Conclusions Untwisting occurs principally during isovolumic relaxation before filling and is markedly enhanced in speed and magnitude by catecholamines. This partial return of the left ventricle to its preejection configuration before mitral valve opening could represent an important mechanism for the release of potential energy stored in elastic elements during the systolic deformation. These myocardial restoring forces would be markedly enhanced by physiological changes consequent to catecholamines such as during exercise, offsetting the concomitant shortening of the filling period.

Independent effects of preload, afterload, and contractility on left ventricular torsion

Shortening of oblique left ventricular (LV) fibers results in torsion. A unique relationship between volume and torsion is therefore expected, and the effects of load and contractility on torsion should be predictable. However, volume-independent behavior of torsion has been observed, and the effects of load on this deformation remain controversial. We used magnetic resonance imaging (MRI) with tagging to study the relationships between load and contractility, and torsion. In ten isolated, blood-perfused canine hearts, ejection was controlled by a servopump: end-diastolic volume (EDV) was controlled by manipulating preload parameters and end-systolic volume (ESV) by manipulating afterload using a three-element windkessel model. MRI was obtained at baseline, two levels of preload alteration, two levels of afterload alteration, and dobutamine infusion. An increase in EDV resulted in an increase in torsion at constant ESV (preload effect), whereas an increase in ESV resulted in a decrease in torsion at constant EDV (afterload effect). Dobutamine infusion increased torsion in association with an increase in LV peak-systolic pressure (PSP), even at identical EDV and ESV. Multiple regression showed correlation of torsion with preload (EDV), afterload (ESV), and contractility (PSP; r = 0.67). Furthermore, there was a close linear relationship between torsion and stroke volume (SV) and ejection fraction (EF) during load alteration, but torsion during dobutamine infusion was greater than expected for the extent of ejection. Preload and afterload influence torsion through their effects on SV and EF, and there is an additional direct inotropic effect on torsion that is independent of changes in volume but rather is force dependent. There is therefore potential for the torsion-volume relation to provide a load-independent measure of contractility that could be measured noninvasively.

Determination of left ventricular mass by magnetic resonance imaging in hearts deformed by acute infarction.

Measurement of left ventricular (LV) mass by magnetic resonance imaging (MRI) is accurate in normal hearts. Because determination of mass by MRI does not require assumptions about ventricular shape, this method may be well suited for evaluating hearts distorted by infarction. To test this hypothesis, gated MRI was performed in 15 dogs before and after acute myocardial infarction. The LV mass of each dog was calculated from five short-axis images acquired at end systole, when shape distortion is greatest, at end diastole, and also from slices at varying phases of the cycle with a multiphase mode that required only one acquisition. Correlation was excellent between actual mass and end-systolic mass before infarction (p less than 0.001, r = 0.98, and SEE = 5.1 g) and after infarction (p less than 0.001, r = 0.97, and SEE = 6.6 g). Likewise, values correlated closely at end diastole before (p less than 0.001, r = 0.96, and SEE = 6.7 g) and after infarction (p less than 0.001, r = 0.94, and SEE = 8.7 g). Surprisingly, measurements of mass by a multiphase mode were also very accurate before (p less than 0.001, r = 0.98, and SEE = 5.1 g) and after (p less than 0.001, r = 0.95, and SEE = 6.49 g) infarction. Therefore, at the same phase and at multiphases of the cardiac cycle, MRI permits accurate determination of LV mass in distorted hearts.

Quantification of and correction for left ventricular systolic long-axis shortening by magnetic resonance tissue tagging and slice isolation.

BackgroundMeasurement of regional left ventricular (LV) function is predicated on the ability to compare equivalent LV segments at different time points during the cardiac cycle. Standard techniques of short-axis acquisition in two-dimensional echocardiography, cine computed tomography, and standard magnetic resonance imaging (MRI) acquire images from a fixed plane and fail to compensate for through-plane motion. The shortening of the left ventricle along its long axis during systole results in planar images of two different levels of the ventricle, leading to error in any derived functional measurements. LV systolic long-axis motion was measured in 19 normal volunteers using MRI. Methods and ResultsWith a selective radio frequency (RF) tissue-tagging technique, three short-axis planes were labeled at end diastole and standard spin-echo images were acquired at end systole in the two- and four-chamber orientations. Persistence of the tags through systole allowed visualization of the intersecting short-axis tags in the long-axis images and allowed precise quantification of long-axis motion of the septum, lateral, anterior, and inferior walls at the base, mid, and apical LV levels. The total change in position along the long axis between end diastole and end systole was greatest at the base, which moved toward the apex 12.8 ± 3.8 mm. The mid left ventricle moved 6.9 ± 2.6 mm, and the apex was nearly stationary, moving only 1.6 ± 2.2 mm (p < 0.001). Having quantified the normal range of long-axis shortening, we developed a technique that isolates a slice of tissue between selective RF saturation planes at end diastole. Combining this with a wide end-systolic image slice, end-systolic images were acquired without contamination of signal from adjacent tissue moving into the imaging plane. This technique was validated in a moving phantom and in normal volunteers. ConclusionsSignificant LV systolic long-axis shortening exists, and this effect is seen the most at the base and the least at the apex. At a given ventricular level, shortening varied significantly according to location. A method using selective saturation pulses and gated spin-echo MRI automatically corrects for this motion and thus eliminates misregistration artifact from regional function analysis.

Accurate systolic wall thickening by nuclear magnetic resonance imaging with tissue tagging: Correlation with sonomicrometers in normal and ischemic myocardium☆

OBJECTIVES This study examined whether the correlation of systolic wall thickening (%WT) by nuclear magnetic resonance (NMR) imaging with wall thickening by sonomicrometry (SM) is improved by using a three-dimensional volume element model of the left ventricular wall. BACKGROUND Left ventricular wall obliquity with respect to the imaging plane causes overestimation of wall thickness by planar imaging techniques. Wall thickness perpendicular to the endocardial surface can be accurately calculated by three-dimensional reconstruction of left ventricular wall segments. METHODS Sonomicrometers were placed transmurally in 11 dogs (left anterior descending artery territory) with an imaging marker, visible on NMR imaging, sewn to the epicardial crystal. Two adjacent NMR short-axis image planes were radially segmented by four perpendicular spin-saturated planes (tags), dividing the myocardium into eight volume elements, one of which contained the sonomicrometer crystal pair. Left ventricular thickness and thickening were calculated by four methods: 1) linear = distance between epicardium and endocardium at midpoint in the segment with the sonomicrometer; 2) planar = area of that segment divided by the mean of the endocardial and epicardial arc lengths; 3) biplanar = average of wall thicknesses calculated by the planar method from the segment with sonomicrometers and the corresponding segment located in the adjacent short-axis imaging plane; and 4) three-dimensional = volume of the element with the sonomicrometers divided by the mean of the endocardial and epicardial surface areas. RESULTS Regressions for all methods using pooled data from control periods and during ischemia: Linear %WT = 0.59 + 1.31 SM%WT (r = 0.71, SEE = 0.28, p < 0.0002) Planar %WT = 1.43 + 1.62 SM%WT (r = 0.87, SEE = 0.19, p < 0.0001) Biplanar %WT = 2.09 + 1.46 SM%WT (r = 0.90, SEE = 0.15, p < 0.0001) Three-dimensional %WT = 0.19 + 1.49 SM%WT (r = 0.95, SEE = 0.10, p < 0.0001) CONCLUSIONS Nuclear magnetic resonance imaging with tissue tagging allows accurate noninvasive assessment of systolic wall thickening. The three-dimensional volume element approach, by accounting for obliquity between the image plane and the left ventricular wall, provides the strongest correlation between NMR imaging and percent systolic wall thickening by sonomicrometer crystals.

Effect of the addition of propranolol to therapy with nifedipine for unstable angina pectoris: a randomized, double-blind, placebo-controlled trial.

The value of the addition of beta-blockers to coronary vasodilator therapy in the treatment of patients with unstable angina at rest is controversial. We conducted a double-blind, randomized, placebo-controlled 4 week trial of propranolol in 81 patients with unstable angina, 39 of whom were assigned to placebo and 42 of whom received propranolol in a dose of at least 160 mg daily. All patients were also treated with coronary vasodilators, including 80 mg nifedipine daily and long-acting nitrates. The incidences of cardiac death, myocardial infarction, and requirement for bypass surgery or coronary angioplasty did not differ between the two groups (propranolol = 16; placebo = 18). The propranolol group had a lower cumulative probability of experiencing recurrent resting angina than the placebo group (p = .013), and over the first 4 days of the trial the mean number of clinical episodes of angina (propranolol 0.9 +/- 0.2, placebo 1.8 +/- 0.3, p = .036), duration of angina (propranolol 15.1 +/- 4.3 min, placebo 38.1 +/- 8.4, p = .014), and nitroglycerin requirement (propranolol 1.1 +/- 0.3 tablets, placebo 3.5 +/- 0.8, p = .003) were also fewer. Continuous electrocardiographic recording for ischemic ST segment changes revealed fewer daily ischemic episodes in the propranolol group (2.0 +/- 0.5) than in the placebo group (3.8 +/- 0.7, p = .03), and a shorter duration of ischemia (propranolol 43 +/- 10 min, placebo 104 +/- 28 min, p = .039). Thus propranolol, in patients with unstable angina, in the presence of nitrates and nifedipine is not detrimental and reduces the frequency and duration of symptomatic and silent ischemic episodes.

Exaggerated Exercise Blood Pressure Is Related to Impaired Endothelial Vasodilator Function

BACKGROUND Persons with high normal blood pressure (BP) or mild hypertension who also have an exaggerated BP response to exercise are at risk for worsening hypertension. The mechanisms that explain this relationship are unknown. We examined the relationships of endothelial vasodilator function and of aortic stiffness with exercise BP. METHODS Subjects were 38 men and 44 women, aged 55 to 75 years, with untreated high normal BP or mild hypertension but otherwise healthy. Exercise was performed on a treadmill. Endothelial vasodilator function was assessed as brachial artery flow-mediated vasodilation (FMD) during reactive hyperemia. Aortic stiffness was measured as pulse wave velocity (PWV). RESULTS Among men, resting systolic BP explained 34% of the variance (P < .01) in maximal exercise systolic BP and FMD explained an additional 11% (P < .01); resting systolic BP explained 23% of the variance in maximal pulse pressure (PP) (P < .01), and FMD explained an additional 10% (P < .01). Among women, resting systolic BP was the only independent correlate of maximal systolic BP (R2 = 0.12, P < .03) and FMD correlated negatively with maximal PP (R2 = 0.12, P < .03). Among men, FMD was the only independent correlate of the difference between resting and maximal systolic BP (R2 = 0.20, P < .02). The FMD was the only independent correlate of the difference between resting and maximal PP among men (R2 = 0.17, P < .03) and among women (R2 = 0.12, P < .03). The PWV did not correlate with exercise BP responses. CONCLUSIONS These results suggest that impaired endothelial vasodilator function may be a mechanism contributing to exercise hypertension and may also be one link between exaggerated exercise BP and worsening hypertension.