Impaired myocardial perfusion in patients with hypertrophic cardiomyopathy: Assessment with digital subtraction coronary arteriography

Summary To study the clinical significance of abnormal myocardial perfusion in patients with hypertrophic cardiomyopathy (HCM), we performed a computerized washout analysis of digital subtraction coronary arteriograms in 28 patients with HCM and 16 control subjects. The contrast disappearance half-life (T 1/2) was calculated from a time-density curve generated in the four sectors of the myocardium perfused by the left anterior descending coronary artery and the mean T 1/2 was calculated by averaging T 1/2 values for these four sectors. Patients with HCM demonstrated longer T 1/2 in the ventricular septal region than control subjects. Thirteen (46%) of the patients with HCM presented abnormally longer mean T 1/2 values, suggesting impaired myocardial perfusion. Family histories of HCM were more frequent in patients with abnormal mean T 1/2 values (92% vs 47%;p<0.05). On the exercise stress test, patients with abnormal T 1/2 values presented significantly lower exercise tolerance with more frequent exercise-induced ST segment depression (62% vs 13%;p<0.05). However, there were no significant differences between the two groups with regard to ventricular wall thickness, left ventricular end-diastolic pressure, or the severity of systolic narrowing of the coronary arteries.These findings suggest that 13 (46%) of the patients with HCM have impaired myocardial perfusion, which may be a manifestation of intramural coronary artery disease in addition to left ventricular hypertrophy, elevated left ventricular end-diastolic pressure, or systolic narrowing of the coronary arteries. Additionally, significant association of the prolonged T 1/2 with a familial occurrence of HCM and depressed exercise tolerance with ST segment depression imply that impaired myocardial perfusion could be an important inherent pathophysiological state leading to myocardial ischemia during exercise.This study was supported in part by a Research Grant for Intractable Diseases from the Ministry of Health and Welfare of Japan.     

Characterization of contraction and perfusion in the lateral border zone between normal and ischemic myocardium following coronary occlusion by myocardial contrast echocardiography

We performed myocardial contrast echocardography with power Doppler imaging during left anterior descending occlusion in 10 dogs, and found that video intensity and dyssynergy in lateral border zones of ischemic myocardium were present, but the video intensity was significantly lower than adjacent nonischemic zones. The results of this study demonstrate that levels of perfusion and contraction, which are intermediate between normal and central ischemic zones, are observed in the border zone with coronary occlusion by myocardial contrast echocardography, and may have implications in identifying myocardium that will be spared necrosis and in measuring ultimate infarct size.     

Comparisons of images simultaneously documented by digital subtraction coronary arteriography and cine coronary arteriography

Using an angiography apparatus capable of simultaneously processing digital subtraction angiograms and cine angiograms, the diagnostic capabilities of both methods for the coronary arteries (DSCAG and Cine-CAG) were compared. 1. Twenty stenotic lesions of the coronary arteries of 11 patients were evaluated using both modalities. The severity of stenosis using DSCAG with a 512 x 512 x 8 bit matrix was semiautomatically measured on the cathode ray tube (CRT) based on enlarged images on the screen of a Vanguard cine projector which were of the same size as those of or 10 times larger than images of Cine-CAG. The negative and positive hard copies of DSCAG images were also compared with those of Cine-CAG. The correlation coefficients of the severity of stenosis by DSCAG and Cine-CAG were as follows: (1) the same size DSCAG images on CRT to Cine-CAG, 0.95, (2) 10 times enlarged DSCAG images on CRT to Cine-CAG, 0.96, and (3) the same size DSCAG images on negative and positive hard copies to Cine-CAG, 0.97. The semiautomatically measured values of 10 times enlarged DSCAG images on CRT and the manually measured values of the same size negative and positive DSCAG images in hard copy closely correlated with the values measured using Cine-CAG. 2. When the liver was superimposed in the long-axis projection, the diagnostic capabilities of DSCAG and Cine-CAG were compared. The materials included 10 left coronary arteriograms and 11 right coronary arteriograms. Diagnostically, DSCAG was more useful than Cine-CAG in the long-axis projection.     

Quantitative evaluation of regional myocardial blood flow by videodensitometric analysis of digital subtraction coronary arteriography in humans

Videodensitometric analysis of digital subtraction coronary arteriography, a new approach for calculating contrast disappearance half-life (T1/2), was assessed in determining regional myocardial blood flow quantitatively. Forty-one patients with coronary artery disease and 12 with angiographically normal coronary arteries underwent digital subtraction coronary arteriography by manual injection of contrast medium into the left main coronary artery. The T1/2 was calculated from a time-density curve generated in the four sectors of the myocardium perfused by the left anterior descending coronary artery. The mean T1/2 value of the four sectors correlated inversely with the great cardiac vein flow measured by the thermodilution method (r = -0.89), and appeared to be a reliable index of myocardial blood flow. The relation of mean T1/2 with percent stenosis of the left anterior descending coronary artery was curvilinear (r = 0.88) and an abnormally high T1/2 occurred in patients with coronary stenosis greater than 75%. In patients with comparable stenosis of the left anterior descending artery, the apical T1/2 was significantly increased in those with impaired apical wall motion, while it was significantly decreased in those with coronary collateral vessels. These findings suggest that regional myocardial blood flow begins to decrease in vessels with greater than 75% stenosis, and that myocardial contraction and collateral flow are additional factors that modify regional myocardial blood flow. Thus, the contrast disappearance half-life (T1/2) derived by computerized washout analysis of digital subtraction coronary arteriograms proved useful as an index for quantitative evaluation of regional myocardial blood flow.     

Factors affecting penetration of retrograde coronary venous injections into normal and ischemic canine myocardium: assessment by contrast echocardiography and digital angiography

Summary This experimental study described myocardial echo contrast enhancement through coronary venous injections. Retrograde administration of renografin was performed in 15 closed-chest dogs. Two-dimensional echocardiography was used to study myocardial echo contrast enhancement before and after coronary artery occlusion. Digital subtraction venography was used to assess delivery, drainage and shunting of the retrograde injectate. Systolic/diastolic blood pressure in the great cardiac vein measured 7±3/1±0.6 mm Hg and increased to 29±11/5±3 after coronary sinus occlusion and to 55±2.3/15±12 mm Hg during coronary sinus contrast injection. Myocardial contrast echo appearance in a midpapillary left ventricular short axis cross-section was limited to the anteroseptal region, extending to 28.4±11.3% of the section circumference after great cardiac vein injections and 35.3±17% after coronary sinus injections (difference NS). After occlusion of the left anterior descending coronary artery, great cardiac vein contrast injections resulted in opacification of 36.6±9.7% of the section circumference (N.S. vs preocclusion control) and opacified most, but not all asynergic segments. After occlusion of the circumflex coronary artery, myocardial echo contrast uptake was restricted to the septum and the anterior wall. The ischemic and asynergic posterolateral myocardial segments were not opacified. Digital subtraction coronary venography revealed rapid drainage of retrogradely injected contrast to the right atrium, in spite of coronary sinus balloon occlusion via venovenous anastomoses.Retrograde coronary venous contrast injections may help define myocardial regions which are accessible with retrograde coronary venous interventions.Dr. Punzengruber was supported by a Grant from the Max Kade Foundation, New York     

Evaluation of myocardial perfusion based on digital subtraction angiocardiography measured contrast medium flow times

The purpose of this study was to discover whether myocardial perfusion can be determined quantitatively by digital subtraction angiocardiography from the passage of contrast medium through the myocardium. Cineangiograms (duration 20 s) were obtained during routine coronary angiography and analyzed by means of a computerized image processing system. Regional myocardial contrast intensity was plotted versus time as a densogram for quantitative assessment. The parameter "medium rise time" showed a good reproducibility (r = 0.92). The average of medium rise time was 2.9 s in well-perfused areas, 3.7 s in less perfused areas, 5.2 s in areas with markedly reduced perfusion and 5.8 s for perfusion defects or scars using Tl-201 scintigrams as reference. The differences between the four groups were significant except between areas of markedly reduced perfusion and perfusion defects or scars (p less than 0.05). The correlation of medium rise time to the extent of the stenosis of the coronary vessel supplying the corresponding myocardial region revealed that the medium rise time on an average was 3.2 s distal to unstenosed vessels, 3.2 s distal to slightly stenosed vessels, 5.4 s distal to highly stenosed vessels and 4.7 s distal to vessel occlusion. The differences between the groups were not significant except between the groups of patients with low and high-grade coronary stenoses. These results indicate that the parameter "medium rise time" of the intensity-time curves determined by digital image processing provides a quantitative assessment of myocardial perfusion from cineangiograms.     

Comparison of digital and cine coronary arteriography

Summary Digital coronary arteriography has advanced from a curiosity to a powerful clinical tool. This development has been motivated by the new imaging demands of interventional cardiology, by the need for quantifying atherosclerotic disease, and by advances in computer and video technology. Digital imaging has now essentially replaced cinefilm for clinical decision making in some catheterization laboratories, although uncertainty remains regarding the diagnostic comparability of the two modalities. Therefore, we compared simultaneously acquired digital and cine arteriograms from 18 patients with multivessel coronary artery disease. Digital utilized pulse-progressive technique, a 512 × 512 pixel × 8 bit image matrix, and no post processing. Four angiographers interpreted the arteriograms, identifying 131 stenotic lesions for measurement with manual calipers. Measurements of percent diameter stenosis by digital and cine correlated closely (r=0.88), but digital estimated stenoses to be significantly more severe than cine (p<0.0001). This difference was most significant in small (< 2 mm diameter) arteries, in branch arteries, and with mild stenoses. The differences between digital and cine were not statistically significant for stenoses > 50% diameter narrowing. Interobserver variability was similar for digital and cine imaging. Thus, unprocessed digital and film-based coronary arteriography yield similar assessments of atherosclerotic stenoses, but the techniques may not be diagnostically interchangeable. This paper discusses the technical advances which have occurred in digital coronary arteriography, the comparability of digital and cine imaging, and the factors which may be responsible for observed differences between the two modalities.     

Identification of viable myocardium by perfusion imaging with intravenous contrast echocardiography after acute myocardial infarction

Myocardial perfusion contrast echocardiography is evolving into an effective method for the evaluation of myocardial blood flow after acute coronary events. The direct injection of ultrasound contrast agents into the aortic and coronary circulation has been shown to accurately identify areas of viable myocardial tissue. Recently, intravenous ultrasound contrast has been found to be useful in detecting microvascular blood flow after the restoration of blood flow in patients with myocardial infarction. We present the case of a patient in whom intravenous ultrasound contrast assisted in the detection of viable myocardial tissue after an acute ischemic syndrome.     

Regional myocardial perfusion in ischemic heart disease assessed by myocardial contrast echocardiography

Myocardial contrast echocardiography is a new cardiovascular imaging technique that can be used to evaluate regional myocardial perfusion. Regional myocardial perfusion was studied in 12 patients with normal coronary arteries, 14 patients with old myocardial infarction, four patients with acute myocardial infarction, and 15 patients with effort angina. Conventional two-dimensional echo imaging was obtained during intracoronary injections of relatively small volumes (2 ml) of agitated Urografin-76. The echo intensities were measured before and after injecting contrast agents and the subtraction images were composed by a high-speed image processor (NEXUS 6400). Clear myocardial images were obtained in 10 of 12 the patients with normal coronary arteries, and they reflected well the epicardial arterial architecture by coronary angiography. In cases of old myocardial infarction, the infarcted areas appeared as contrast defects in seven and as slightly enhanced areas in three of the 10 patients. In cases of acute myocardial infarction, contrast defect areas in the myocardial images were less in two cases of successful early coronary thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). However, contrast defects remained unchanged despite good recanalization in one case of delayed PTCA. In cases of effort angina, anginal attacks were successfully induced by rapid atrial pacing in six of the 15 patients. In four of the six patients, contrast enhancement in myocardial imaging during anginal attack decreased more in the endocardial than in the epicardial myocardium, possibly reflecting subendocardial ischemia. It is concluded that this technique can identify regional myocardial perfusion, which is not revealed by coronary angiography, and it is therefore useful for the clinical analysis of ischemic heart disease.     

Residual myocardial perfusion in reversibly damaged myocardium by dipyridamole contrast echocardiography

In patients with previous myocardial infarction and left ventricularasynergy, dipyridamole infusion may have the capacity to unmaskmyocardial viability through transient recovery of contractilefunction in asynergic segments. The purpose of this study wasto assess simultaneous changes in myocardial perfusion and LVfunction—elicited by dipyridamole infusion—in infarcted,asynergic segments. The echo contrast agent Albunex was injectedinto the left coronary artery of 19 patients (17 males, age49–70 years) with previous myocardial infarction and baselineleft ventricular asynergy, both before and after dipyridamoleinfusion (up to 0·56 mg. kg^–1, i.v.). Analysiswas not possible in three patients due to inadequate image qualityand in two due to weak contrast. There were no major adverseevents, or changes in vital signs or demonstrated on the electrocardiogram.After dipyridamole, 7/14 patients, showed an improvement inregional function of asynergic segments (‘responders’),whereas seven patients did not (‘non-responders’).Among non-responders, five had a myocardial perfusion deficitcorresponding to 41% of the total left ventricular area beforedipyridamole and to 38% after dipyridamole. No baseline perfusiondeficits were observed in the remaining two non-responders;one of these, however, developed transient asynergy and perfusiondeficit after dipyridamole. Among responders, five showed anormal perfusion pattern, both before and after dipyridamole,while the remaining two showed a perfusion deficit which markedlydecreased after dipyndamole (from 32% to 13% of total left ventriculararea). Thus, residual contractile reserve of asynergic, infarctedventricular segments appears to be associated with myocardialperfusion either preserved at baseline or recruitable by a coronarydilator stimulus.     

Comparison of myocardial perfusion assessments by digital subtraction angiography with those of left ventricular wall dynamics

In clinical and experimental studies we assessed images of digital subtraction coronary angiography (DSA) for evaluating regional myocardial perfusion. Myocardial perfusion was assessed by injecting contrast medium into the coronary artery, and by imaging the regional myocardium using DSA. On the time-density curve obtained from the myocardial region of interest, we calculated the time to peak concentration (TPC) and the exponential washout rate (T). TPC and T were measured in five patients with stable effort angina pectoris (AP) and left anterior descending (LAD) lesions before and after percutaneous transluminal coronary angioplasty (PTCA). The values of 1/T increased significantly from 0.09 +/- 0.02 l/sec to 0.21 +/- 0.04 l/sec (p less than 0.01) after PTCA, but l/TPC did not change. No significant difference in ejection fractions was observed between the patients with AP and the normal subjects (n = 7), while the regional percent area shrinkage in the anterolateral and apical regions supplied by the LAD was significantly decreased in the patients with AP compared with those of normal subjects (anterolateral: 39.8 +/- 8.8% vs 51.3 +/- 6.8%, apical: 36.6 +/- 8.4% vs 52.4 +/- 13.4%, both p less than 0.01). In 10 anesthetized dogs with varying degrees of reduction in the left circumflex coronary artery (LCX) blood flow (CBF: categories of stenosis (S1-S5), we compared 1/TPC and 1/T with regional myocardial function (systolic wall thickening: %WTh). With varying LCX stenosis, there were no significant changes in heart rate and mean aortic pressure and significant linear correlations were observed between %WTh and 1/TPC (r = 0.51), between %WTh and 1/T (r = 0.55). At S1 (CBF: 100-90% of the control), neither %WTh nor 1/TPC differed from that of the controls, but 1/T was significantly decreased (80% of the controls, p less than 0.01). From S3 (CBF: 79-60%) to S5 (CBF: 39-0%), %WTh, 1/TPC and 1/T were significantly decreased from those of the control levels (all p less than 0.01). However, at S5 (CBF: 39-0%) the values of 1/TPC (71% of controls) and 1/T (33%) did not differ from those at S4; whereas, %WTh was markedly reduced and the systolic thinning of the ventricular wall occurred at S5. Therefore, in critical coronary stenosis, 1/T was more sensitive than 1/TPC or wall dynamics for assessing myocardial ischemia. Both 1/TPC and 1/T, as well as %WTh, were useful for assessing moderate myocardial ischemia; however, these DSA indices had considerable limitations for evaluating the severity of myocardial ischemia when CBF was markedly reduced.     

Outcomes in patients with abnormal myocardial perfusion imaging and normal coronary angiogram

A subset of subjects undergoing myocardial perfusion imaging has perfusion abnormalities that are subsequently labeled false positive based on coronary angiography. We evaluated the long-term prevalence of cardiovascular events in these patients. We retrospectively identified 48 patients who had reversible perfusion abnormalities with myocardial perfusion imaging and normal coronary angiography. Patients with known coronary artery disease, left ventricular dysfunction, valvular disease, and cardiomyopathy were excluded. Patient follow-up, conducted for at least 3 (mean interval, 7.4) years from the index myocardial perfusion imaging, was accomplished by a review of medical records and telephone interviews. Study endpoints were cardiovascular events defined as sudden cardiac death, myocardial infarction, percutaneous coronary revascularization, coronary artery bypass grafting, and cerebrovascular or peripheral revascularization. Thirty-one percent (15 of 48) of the patients had cardiovascular events. Six of the 48 patients had coronary events. These patients had abnormal myocardial perfusion imaging and normal coronary angiogram. The time between myocardial perfusion imaging and coronary event was 0.5 to 8.67 years. There was a strong correlation between the regions of original perfusion abnormality and the ultimate coronary ischemia or revascularization. Abnormal findings on myocardial perfusion imaging may predict a higher prevalence of coronary and peripheral vascular events than suggested by a normal coronary angiogram.     

Densitometric studies in digital subtraction angiography: assessment of pulmonary and myocardial perfusion

The technical improvement of digital imaging systems has provided for roentgen densitometric analysis of radiographic image sequences. Thereby, regional and temporal measurements of the amount of contrast medium have been performed for comparative studies in angiocardiography. The use of digital image subtraction for densitometric evaluation is specifically advantageous because misregistration by motion artefacts can be circumvented. Furthermore, enhancement of faintly opacified circulatory structures assists in the detection and outlining of the regions of interest. Methods of digital densitometry are described utilizing large "densitometric areas" for the evaluation of pulmonary perfusion symmetry. Similarly, coronary flow distribution data have been established in experimental studies. Regional measurements of myocardial contrast accumulation allowed for perfusion studies in absolute units of volume flow (ml/min) of the three main coronary arterial vessels. Future application of the latter technique is expected to facilitate coronary flow reserve measurements in the clinical setting.     

New imaging technology: measurement of myocardial perfusion by contrast echocardiography

Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.     

Evaluation of myocardial perfusion abnormality by profile analysis for digital subtraction angiogram

For quantitative estimation of ischemia, ECG-synchronized digital subtraction angiography was performed for selective coronary arteriography. The authors obtained sequential myocardial perfusion images at the arterial, capillary, and venous phases. Profile densitometry was performed along the cross section perpendicular to the long axis of the left ventricle to assess regional myocardial perfusion at the capillary phase quantitatively. By this densitometry, the volumes of vascular bed perfused by the left coronary artery could be estimated, and further, nontransmural myocardial infarction could be differentiated from transmural myocardial infarction through the profile of its density curve. This method appears to be useful for the analysis of myocardial perfusion of ischemic heart disease.     

Assessment of coronary hemodynamics and myocardial perfusion in patients with syndrome X by digital subtraction angiography and 201Tl-myocardial scintigraphy]

To evaluate coronary hemodynamics and myocardial perfusion, left coronary digital subtraction angiography (DSA) and Tl-201 myocardial scintigraphy were performed in patients with syndrome X. The coronary circulation time (CCT) was significantly prolonged after the injection of isosorbide dinitrate and contrast medium i.c. Apical T1/2 was also prolonged on ergonovine malate provocation test. We suspected that the vascular response of the coronary peripheral artery was impaired, and microvascular spasm probably existed in patients with syndrome X. The prevalence of abnormal myocardial perfusion defect on exercise Tl-201 SPECT in syndrome X was very high, and coronary hemodynamics was significantly disturbed in the group of syndrome X with abnormal Tl-201 SPECT. Tl-201 lung/heart count ratio significantly increased in syndrome X on treadmill test. Because of this, exercise induced left ventricular dysfunction was suspected. We concluded that the main pathophysiological finding of impaired coronary circulation in syndrome X was microvascular spasm.     

Regional myocardial coronary blood flow reserve in hypertrophic cardiomyopathy assessed by digital subtraction coronary angiography

Previous observations suggest the presence of ischemia in the disproportionately thickened interventricular septum (IVS) of patients with hypertrophic cardiomyopathy (HCM), although the details remain obscure. Utilizing digital subtraction coronary angiography (DSA) with LAO projection before and after intracoronary papaverine (P) injection, we evaluated regional myocardial coronary blood flow reserve (rMFR) consecutively 18 patients with HCM, and compared it with that of 8 patients without apparent cardiac abnormality (C). Time-density curves were obtained from digital angiograms of the myocardial region of interest. We measured peak contrast density (Cm) and time to peak contrast (Tm). An index of rMFR was calculated as the quotient of Cm/Tm before and after P. In HCM, rMFR in IVS and apex was significantly lower than that of C (Mid-IVS: 1.9 +/- 0.5 vs 3.9 +/- 0.5, p less than 0.001; Low-IVS: 2.0 +/- 0.5 vs 4.4 +/- 0.9, p less than 0.001; Apex: 2.0 +/- 0.7 vs 4.5 +/- 1.6, p less than 0.01). There was correlation between the impairment of rMFR and the extent of hypertrophy in HCM. In conclusion, we could state that, in HCM, the region of impaired myocardial coronary blood flow reserve is localized. In HCM, DSA is useful in evaluating myocardial coronary blood flow reserve.