Eldad Rechavia

Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography

BackgroundOxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. Methods and ResultsThe technique involves the administration of 150-labeled carbon dioxide (C1502) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements ofMBF with PET and y-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 ± 0.08 ml/g/min and 3.52 ± + 1.12 ml/g/min, respectively; p≤0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 ± 0.23 and 0.93 ± 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 ± 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 ± 0.27 ml/g/min (p<0.001). ConclusionsPET with C1502 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients. (Circulation 1991;83:875–885)

A new strategy for the assessment of viable myocardium and regional myocardial blood flow using 15O-water and dynamic positron emission tomography.

BackgroundWe have developed a new measure of myocardial viability, the water-perfusable tissue index (PTI), which is calculated from transmission, C1550, and H215O positron emission tomography (PET) data sets. It is defined as the proportion of the total anatomical tissue within a given region of interest (ROI) that is capable of rapidly exchanging water and has units g (perfusable tissue)/g (total anatomical tissue). The aim of this study was to assess the prognostic value of PMI in predicting improvement in regional wall motion after successful thrombolysis for acute myocardial infarction (AMI) and to measure the myocardial blood flow to the perfusable tissue (MBFp, ml/min/g [perfusable tissue]). Furthermore, PTI was compared with 18FDG metabolic imaging in patients with old myocardial infarction (OMI). Methods and ResultsPET scans were performed in healthy volunteers (group 1, n = 8), patients with OMI (group 2, n = 15), and in patients who were successfully thrombolysed after an AMI (group 3, n = 11). Systolic wall thickening was measured by two-dimensional echocardiography within 2–4 days of AMI and after 4 months to assess contractile recovery. In the healthy volunteers, MBFp was 0.95±0.13 ml/min/g (perfusable tissue). PTI in these regions was 1.08±0.07 g (perfusable tissue)/g (total anatomical tissue), which was consistent with all normal myocardium being perfusable by water. In the OMI group, the ratio of the relative 18FDG activity to the relative MBFp defect (metabolism-flow ratio) was calculated for each asynergic segment. Regions in which the metabolism-flow ratio was ≥1.20 were considered reversibly injured, whereas those in which the ratio was < 1.20 were deemed irreversibly injured. PTI in the former group of regions (n = 9) was 0.75±0.14 g (perfusable tissue)/g (total anatomical tissue) and was significantly higher than in irreversibly injured regions (n = 6) (0.53±0.12 g [perfusable tissue]/g [total anatomical tissue], p<0.01). Values of MBFp were similar in these segments. Seven of 12 segments in the AMI patients showed improved systolic wall thickening on follow-up. PTI in these recovery segments was 0.88±0.10 g (perfusable tissue)/g (total anatomical tissue) (p = NS versus control). PTI in the nonrecovery regions was 0.53±0.11 g (perfusable tissue)/g (total anatomical tissue), which was similar to the segments in group 2 in which 18FDG uptake was absent. MBFp was similar in both the recovery and nonrecovery segments in the subacute phase. ConclusionsThese data indicate that PTI may be a good prognostic indicator for the recovery of contractile function after successful thrombolysis and show that myocardial viability may be assessed by PET without metabolic imaging.

Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease

Myocardial blood flow (MBF) was measured using continuous inhalation of oxygen-15-labeled carbon dioxide, and positron emission tomography before and after intravenous dipyridamole in 13 patients with syndrome X (angina pectoris, angiographically normal coronary arteries, positive exercise test and negative ergonovine test), 7 healthy subjects and 8 patients with 1-vessel coronary artery disease (CAD). In patients with syndrome X, baseline MBF was greater than in healthy subjects and patients with CAD (1.24 +/- 0.27 vs 0.87 +/- 0.07 and 1.03 +/- 0.23 ml/g/min, respectively; p < 0.05), and more heterogeneous (34 +/- 7 vs 26 +/- 5 and 25 +/- 6, respectively; p < 0.05) as assessed by the coefficient of variation among myocardial regions < or = 2.3 cm3. After dipyridamole, MBF in patients with syndrome X was similar to that in healthy subjects (2.95 +/- 0.75 vs 3.40 +/- 0.82 ml/g/min; p = NS) and greater than in patients with CAD (1.78 +/- 0.76 ml/g/min; p < 0.05). However in patients with both syndrome X and CAD, MBF was more heterogeneous than in healthy subjects (48 +/- 12 and 48 +/- 11, respectively, vs 30 +/- 7; p < 0.01). Thus, in patients with syndrome X, MBF is abnormally heterogeneous both at baseline and after dipyridamole. These findings are compatible with the presence of dynamic alterations of small coronary arteries. Because these alterations appear to be very sparse within the myocardium, they can be undetected when myocardial perfusion, function and metabolism are assessed using conventional methods that are unable to detect small myocardial regions.

Implications of inferior ST-segment depression in anterior acute myocardial infarction: Electrocardiographic and angiographic correlation

This study assesses the significance of inferior ST-segment depression during anterior acute myocardial infarction (AMI) by investigating the relationship between inferior ST-segment depression and (1) the site of the left anterior descending (LAD) coronary artery lesion and (2) ST-segment deviation in the various anterior and lateral leads. We studied 126 patients with anterior AMI who underwent coronary angiography within 21 days of hospitalization. The admission 12-lead electrocardiograms were evaluated for ST-segment amplitude in each lead at 0.08 second after the J-point. Coronary angiography was evaluated for the site and severity of luminal narrowing of the coronary arteries. The site of the culprit lesion in the LAD artery, relative to the origin of the first septal and diagonal branches, was determined. In four patients no lesion was identified in the LAD artery. Of the remaining 122 patients, 40 and 53 patients had a LAD artery lesion proximal to the first septal and first diagonal branches, respectively. Additional luminal narrowing (> or = 70% of diameter) was found in the circumflex and the right coronary arteries in 27 and 37 patients, respectively. ST-segment depression of > 1 mm in leads II, III, and aVF was noted in 24, 29, and 24 patients, respectively. The prevalence of a LAD artery preseptal and prediagonal lesion was higher in patients with inferior ST-segment depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole vasodilator response after human orthotopic heart transplantation : quantification by oxygen-15-labeled water and positron emission tomography

To assess coronary vasodilator reserve after orthotopic heart transplantation, regional myocardial perfusion was measured with oxygen-15-labeled water and dynamic positron emission tomography in 14 cardiac allograft recipients who were not experiencing rejection and who had no angiographic evidence of epicardial coronary sclerosis 15 to 73 months (mean +/- SD 43 +/- 19) after transplantation (group I). Twelve normal men with an average age of 31 years (group II) served as a control group. Regional perfusion was measured at rest and after the intravenous administration of 0.6 mg/kg body weight of dipyridamole. Rest regional myocardial blood flow was homogeneously distributed throughout the left ventricle and was significantly higher in transplant recipients (mean 1.16 +/- 0.26 ml/g per min [range 0.8 to 1.73] than in normal subjects (mean 0.85 +/- 0.13 ml/g per min [range 0.57 to 0.99]; p = 0.001) as was rest heart rate-systolic blood pressure product (rate-pressure product 11,255 +/- 2,540 vs. 7,073 +/- 1,306; p less than 0.001). After dipyridamole, perfusion in the transplant recipients was homogeneous and slightly lower (2.73 +/- 1.03 vs. 3.40 +/- 1.09 ml/g per min; p = NS), whereas rate-pressure product was slightly higher (12,179 +/- 2,266 vs. 10,885 +/- 1,895; p = NS) than the value in normal subjects. Dipyridamole vasodilator response (dipyridamole/rest myocardial blood flow) ranged from 1.23 to 4.92 (mean 2.50 +/- 1.13) in group I and from 2.65 to 5.45 (3.97 +/- 0.89) in group II (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated mid-anterior myocardial infarction: a special electrocardiographic sub-type of acute myocardial infarction consisting of ST-elevation in non-consecutive leads and two different morphologic types of ST-depression

UNLABELLEDnWe describe eight patients with a distinct electrocardiographic pattern of anterior wall myocardial infarction characterized by three main features: (1) a pattern of transmural ischemia (ST-elevation with positive T-wave) in non-consecutive leads: a VL and V2, and two different types of ST-depression; (2) a pattern of true reciprocal changes (ST-depression and negative T-wave) in III and a VF; (3) a pattern of sub-endocardial ischemia (ST-depression with positive T-wave) in V4-5, while ST in V3 was either isoelectric or depressed. We characterize the electrocardiographic features and correlate them with the echocardiographic, radionuclide, and angiographic data. All patients admitted to the coronary care unit from January 1990 to April 1992 with evolving acute myocardial infarction were evaluated prospectively. Patients whose admission electrocardiogram met the description above were included. The electrocardiographic evolution, echocardiographic, Technetium MIBI tomography, and coronary angiography are described. Of 471 patients with acute anterior wall myocardial infarction, admitted to the coronary care unit during the study period, eight patients met the inclusion criteria (1.7% of acute anterior wall myocardial infarction). Echocardiographic studies revealed mid-anterior hypokinesis in two patients, anterior and apical hypokinesis in one, and no wall motion abnormality in four patients. Technetium MIBI tomography, done in five patients, was consistent with mid-anterior or midanterolateral infarction without involvement of the septum or apex. Coronary angiography, performed in seven patients, demonstrated significant obstruction of the first diagonal branch in all of the patients. In four patients, the diagonal occlusion was the only significant coronary lesion in the left coronary artery.nnnCONCLUSIONnMost of the anterior myocardial infarctions also involve the septal and apical regions. Anterior wall myocardial infarctions limited to the mid-anterior or mid-anterolateral wall, without apical or septal wall involvement are relatively rare. This study describes a special electrocardiographic form of anterior wall acute myocardial infarction. This distinct electrocardiographic pattern represents true mid-anterior wall myocardial infarction, caused by occlusion of a first diagonal branch of the left anterior descending coronary artery. The septal and apical regions are not involved because the blood supply via the left anterior descending artery is not interrupted.

Enhanced myocardial 18F-2-fluoro-2-deoxyglucose uptake after orthotopic heart transplantation assessed by positron emission tomography.

OBJECTIVESnWe sought to assess the relation between glucose metabolism, myocardial perfusion and cardiac work after orthotopic heart transplantation.nnnBACKGROUNDnThe metabolic profile of the transplanted cardiac muscle is affected by the lack of sympathetic innervation, impaired inotropic function, chronic vasculopathy, allograft rejection and immunosuppressive therapy. In relation to myocardial perfusion and cardiac work, glucose metabolism has not previously been studied in heart transplant recipients.nnnMETHODSnRegional myocardial blood flow (ml.min-1.g-1) and 18F-2-fluoro-2-deoxyglucose (18FDG) uptake rate (ml.s-1.g-1) were measured after an overnight fast in 9 healthy male volunteers (mean age +/- SD 32 +/- 7 years) and in 10 male patients (mean age 50 +/- 10 years) who had a nonrejecting heart transplant, normal left ventricular function and no angiographic evidence of epicardial coronary sclerosis. Measurements were made by using dynamic positron emission tomography (PET) with 15O-labeled water and 18FDG, respectively. Heart rate and blood pressure were also measured for calculation of rate-pressure product.nnnRESULTSn18FDG uptake was similar in all heart regions in the patients and volunteers (intrasubject regional variably 12 +/- 8% and 16 +/- 12%, respectively, p = 0.51). Regional myocardial blood flow was similarly evenly distributed (intrasubject regional variability 14 +/- 10% and 12 +/- 8%, respectively, p = 0.67). Mean 18FDG uptake and myocardial blood flow values for the whole heart are given because no regional differences were identified. 18FDG uptake was on average 196% higher in the patients than in the volunteers (2.90 +/- 1.79 x 10(-4) vs. 0.98 +/- 0.38 x 10(-4) ml.s-1.g-1, p = 0.006). Regional myocardial blood flow and rate-pressure product were similarly increased in the patient group, but by only 41% (1.14 +/- 0.3 vs. 0.81 +/- 0.13 ml.min-1.g-1, p = 0.008) and 53% (11,740 +/- 2,830 vs. 7,689 +/- 1,488, p = 0.001), respectively.nnnCONCLUSIONSn18FDG uptake is homogeneously increased in normally functioning nonrejecting heart transplants. This finding suggests that glucose may be a preferred substrate in the transplanted heart. The magnitude of this observed increase is significantly greater than that observed for myocardial blood flow or cardiac work. In the patient group, the latter two variables were increased to a similar degree over values in control hearts, indicating a coupling between cardiac work load and myocardial blood flow. The disproportionate rise in 18FDG uptake may be accounted for by inefficient metabolic utilization of glucose by the transplanted myocardium or by the influence of circulating catecholamines, which may stimulate glucose uptake independently of changes in cardiac work load.

DELETERIOUS EFFECTS OF INTRAVENOUS VERAPAMIL IN WOLFF-PARKINSON-WHITE PATIENTS AND ATRIAL FIBRILLATION

SummaryThree patients presented to the emergency room with atrial fibrillation and fast ventricular response with wide preexcited QRS complexes (Wolff-Parkinson-White syndrome). All three patients received intravenous verapamil (5–10mg). The first patient developed ventricular fibrillation requiring several defibrillations; the second patient developed severe hemodynamic deterioration requiring urgent cardioversion; in the third patient a marked increment in the ventricular response was noted, however, there was no hemodynamic impairment.Verapamil may cause detrimental results when given to patients with the Wolff-Parkinson-White syndrome and atrial fibrillation. Its administration should therefore be considered as an absolute contraindication in these patients.

The significance of a dipyridamole induced 99mTc-MIBI perfusion abnormality on single photon emission tomography: a quantitative validation with labelled water and positron emission tomography

To relate technetium-99m 2-methoxy-isobutylisonitrile (99mTc-MIBI) uptake to regional myocardial blood flow (rMBF), 99mTc-MIBI single photon emission tomography (SPET) and H215O positron emission tomography (PET) scans were obtained at rest and after dipyridamole infusion in six patients with single vessel coronary artery disease. 99mTc-MIBI and H215O data sets were created for each segment perfused by the stenotic vessel and for a normal reference area, assigning regions on the SPET tomograms to comparable regions on the PET by similar transaxial image reconstructions. All patients demonstrated post-dipyridamole 99mTc-MIBI perfusion defects in the territories supplied by the stenotic arteries. Resting rMBF in these regions was slightly lower than that in the normal areas (0.82±0.05 vs 0.90±0.09 ml/g/min, P=NS). A 43%±14% reduction in 99mTc-MIBI activity in the area at risk was coupled with on average a 60%±9% reduction in post-dipyridamole rMBF compared with control regions (0.98±0.08 vs 2.52±0.51 ml/g/min, P<0.001). Thus, SPET assessment of 99mTc-MIBI uptake tends to underestimate the perfusion contrast between areas with normal and areas with low coronary vasodilatory reserve when compared to PET. However, these findings may still not affect the clinical usefulness of 99mTc-MIBI and more extensive studies are required to confirm these results in the clinical environment.

S-T segment depression in right-sided precordial leads during acute inferior wall infarction.

Right-sided chest leads (V3-V4R) were recorded in the early stages of first inferior wall acute myocardial infarction (AMI) in 100 consecutive patients. Nine patients (9%) presenting with S-T segment depression (greater than 1 mm) in these leads were subsequently studied by echocardiography and radionuclear angiography. In this group, there were 5 patients with intact right ventricular (RV) function and 4 other patients with clinical findings compatible with RV infarction. We suggest that one should not rule out RV involvement when S-T segment depression rather than elevation is seen in the right precordial leads in the presence of inferior wall AMI. An individual assessment for RV infarction is recommended when this pattern is apparent on the ECG.