Alfredo R. Galassi

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)

Classification of coronary artery bifurcation lesions and treatments: Time for a consensus!

Background: Percutaneous coronary intervention (PCI) of coronary bifurcation lesions remains a subject of debate. Many studies have been published in this setting. They are often small scale and display methodological flaws and other shortcomings such as inaccurate designation of lesions, heterogeneity, and inadequate description of techniques implemented. Methods: The aim is to propose a consensus established by the European Bifurcation Club (EBC), on the definition and classification of bifurcation lesions and treatments implemented with the purpose of allowing comparisons between techniques in various anatomical and clinical settings. Results: A bifurcation lesion is a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant side branch. The simple lesion classification proposed by Medina has been adopted. To analyze the outcomes of different techniques by intention to treat, it is necessary to clearly define which vessel is the distal main branch and which is (are) the side branche(s) and give each branch a distinct name. Each segment of the bifurcation has been named following the same pattern as the Medina classification. The classification of the techniques (MADS: Main, Across, Distal, Side) is based on the manner in which the first stent has been implanted. A visual presentation of PCI techniques and devices used should allow the development of a software describing quickly and accurately the procedure performed. Conclusion: The EBC proposes a new classification of bifurcation lesions and their treatments to permit accurate comparisons of well described techniques in homogeneous lesion groups.

Role of adenosine in pathogenesis of anginal pain.

The intravenous infusion of adenosine provokes anginalike chest pain. To establish its origin, an intracoronary infusion of increasing adenosine concentrations was given in 22 patients with stable angina pectoris. During adenosine infusion, 20 patients had chest pain without electrocardiographic signs of ischemia. They all reported that the chest pain was similar to their usual anginal pain. In 10 of the 22 patients adenosine was also infused into the right atrium, but it never produced symptoms at the doses that had provoked chest pain during intracoronary infusion. In seven other patients, the intracoronary adenosine infusion was repeated after intravenous administration of aminophylline, an antagonist of adenosine P1-receptors. Aminophylline decreased the severity of adenosine-induced chest pain (assessed with a visual analog scale) from 42 +/- 22 to 23 +/- 17 mm (p less than 0.002). In the remaining five of the 22 patients, monitoring of blood oxygen saturation in the coronary sinus during intracoronary adenosine administration showed that maximum coronary vasodilation was achieved at doses lower than those responsible for chest pain. A single-blind, placebo-controlled, randomized trial of the effect of aminophylline on exercise-induced chest pain was also performed in 20 other patients with stable angina. Aminophylline, compared with placebo, decreased the severity of chest pain at peak exercise from 67 +/- 21 to 51 +/- 23 mm (p less than 0.02), despite the achievement of a similar degree of ST-segment depression. Finally, the effect of intravenous adenosine was compared in 10 patients with predominantly painful myocardial ischemia and in 10 patients with predominantly silent ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club.

Georgios Sianos1*, MD, PhD, FESC; Gerald S. Werner2, MD, PhD, FESC, FACC, FSCI; Alfredo R. Galassi3, MD, FESC, FACC, FSCAI; Michail I. Papafaklis4, MD, PhD; Javier Escaned5, MD, PhD, FESC; David Hildick-Smith6, MD, FESC; Evald Hoj Christiansen7, MD, PhD; Anthony Gershlick8, MD, FRCP, FESC; Mauro Carlino9, MD, FESC; Angelos Karlas1, MD; Nikolaos V. Konstantinidis1, MD; Salvatore D. Tomasello3, MD; Carlo Di Mario10, MD, PhD, FRCP, FESC; Nicolaus Reifart11, MD, PhD, FESC for the EuroCTO Club

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.

Myocardial Ischemia Caused by Distal Coronary-Artery Constriction in Stable Angina Pectoris

BACKGROUND In patients with stable coronary artery disease, the ischemic threshold for the production of effort-related angina is often quite variable. Although this feature is commonly attributed to changes in the caliber of coronary arteries at the site of stenosis, it could also be caused by the constriction of distal vessels, collateral vessels, or both. METHODS In order to test this hypothesis, we studied 11 patients with stable angina, total occlusion of a single coronary artery that was supplied by collateral vessels, normal ventricular function, no evidence of coronary-artery spasm, and no other coronary stenoses. These conditions precluded the modulation of coronary flow by vasomotion at the site of the coronary stenosis. RESULTS The ischemic threshold--assessed by multiplying the heart rate by the systolic blood pressure at a 1-mm depression of the ST segment during exercise testing--increased by 19 percent after the administration of nitroglycerin (P less than 0.05) and decreased by 18 percent after the administration of ergonovine (P less than 0.01). Ambulatory electrocardiographic monitoring of the patients when not receiving treatment detected 73 ischemic episodes that, in keeping with the history, showed variations of 25 to 52 beats per minute in the heart rate at a 1-mm depression of the ST segment; 12 episodes of sinus tachycardia exceeded the lowest ischemic heart rate by a mean (+/- SD) of 22 +/- 13 beats per minute without ST-segment depression. Furthermore, 21 ischemic episodes occurred at a heart rate more than 25 beats per minute below that at a 1-mm depression of the ST segment during exercise testing. Delayed and reduced filling of collateral and collateralized vessels associated with depression of the ST segment similar to that observed during ambulatory monitoring was detected on angiographic evaluation after the intracoronary administration of ergonovine in three patients. CONCLUSIONS We propose that the constriction of distal coronary arteries, collateral vessels, or both may cause myocardial ischemia in patients with chronic stable angina.

Incremental Prognostic Value of Technetium-99m-Tetrofosmin Exercise Myocardial Perfusion Imaging for Predicting Outcomes in Patients With Suspected or Known Coronary Artery Disease

Technetium-99m (Tc-99m)-tetrofosmin is a radio isotope that has been shown to be an accurate alternative to thallium-201 for detecting coronary artery disease. However, its prognostic value is less well determined. To this end, 459 consecutive patients (mean age 58 +/- 10 years) with suspected or known coronary artery disease underwent exercise single-photon emission tomography Tc-99m-tetrofosmin scintigraphy. Follow-up, defined as the time from scanning until a soft event (revascularization procedures), a hard event (myocardial infarction and cardiac death), or patient response, lasted up to 78 months (median 38). An ischemic scintigraphic perfusion score, which takes into account both the extent and severity of reversible perfusion defects, was calculated to estimate the severity of perfusion abnormalities. Patients with normal scans were at low risk of events (yearly hard event rate 0.5% and soft event rate 0.9%). The rate of outcomes increased significantly with abnormal scans (yearly hard event rate 4.9% and soft event rate 10.3%). Statistical analysis using the Kaplan-Meyer survival curves showed a significant difference in event-free survival between patients with normal and abnormal scans. With use of Cox proportional-hazards analysis, after adjusting for prescan information, nuclear data provided incremental prognostic value for hard events (clinical and exercise data vs nuclear data; chi-square = 15.5 vs 33.4, p <0.001). Exercise single-photon emission tomographic scintigraphy using Tc-99m-tetrofosmin provides significant independent information on the subsequent risk of hard and soft events. The annual event rate for hard and soft events is <1% for patients with a normal scan. Furthermore, this tracer yields incremental prognostic information in addition to that provided by clinical and exercise data for hard events.

Pain threshold and tolerance in women with syndrome X and women with stable angina pectoris.

A recent report showed that during Holter monitoring of patients with syndrome X (typical anginal pain, positive exercise test response [at least 0.1 mV of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries), 50% of episodes of ischemic ST-segment depression were painful. This proportion is considerably higher than that in patients with chronic stable angina, which is about 30%. A significantly lower threshold and tolerance to painful stimuli was seen in a group of patients with chronic stable angina in whom 50% of episodes were painful compared with a group in whom only 5% of episodes were silent. Hence, patients with syndrome X may have enhanced sensitivity to painful stimuli. To investigate whether this difference was due to a lower threshold for painful stimuli in general, 12 patients with syndrome X and 10 (age- and sex-matched) with chronic stable angina were studied using the same battery of painful stimuli. Patients with syndrome X had a significantly lower threshold and tolerance for forearm ischemia (-36%, p less than 0.05, and -40%, p less than 0.001) and electrical skin stimulation (-37%, p less than 0.01, and -35%, p less than 0.001); the cold pressor test did not show significant differences (-7%, p = 0.391, and -1%, p = 0.818). Thus, patients with syndrome X in this study had significantly lower threshold and tolerance values for forearm ischemia and for electrical skin stimulation. These differences in sensitivity to pain may partly explain a higher incidence of painful ischemic episodes detected by ambulatory electrocardiographic monitoring during unrestricted daily life.

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.

Long‐term outcomes of bifurcation lesions after implantation of drug‐eluting stents with the “mini‐crush technique”

Objectives: To evaluate clinical and angiographic long‐term outcome of “the mini‐crush” technique for treating bifurcation lesions. Background: Despite proven efficacy of drug‐eluting stent (DES) within most lesions subsets, bifurcation lesions continue to exhibit high restenosis rate using current DES stenting technique. Methods: We report a new stenting technique which was employed in 45 consecutive patients (52 lesions) between April 2004 and July 2005 to treat true bifurcation lesions using DES in both branches. Results: Using this technique procedural success was obtained in 100% of cases, without complications and with excellent angiographic result in 96.1% and 98.1% of main vessel and side branch. Preprocedure reference vessel diameter and minimal lumen diameter (MLD) were 2.68 ± 0.48 and 0.90 ± 0.55 mm for the main branch, respectively and 2.28 ± 0.34 and 1.14 ± 0.47 mm for the side branch, respectively. Postprocedure MLD was 2.56 ± 0.39 mm for the main branch and 2.16 ± 0.29 mm for the side branch. There were no in‐hospital major adverse cardiac events (MACE). At 72 days after procedure there was one case of side branch stent thrombosis (2.2%), which resulted in non Q‐wave MI. Angiographic follow up was obtained in 100% of patients at 7.5 ± 1.3 months. Target lesion revascularization (TLR) was 12.2%; no death and Q‐wave MI were observed; reference vessel diameter and MLD for the main branch were 2.79 ± 0.51 and 1.99 ± 0.65 mm respectively and for the side branch 2.28 ± 0.40 and 1.63 ± 0.48 mm respectively. Restenosis rate in the main branch was 12.2% while in the side branch was 2.0%. Conclusions: In‐hospital outcome indicates that the mini‐crush technique for bifurcation lesions with DES can be easily performed. It provides very low total MACE rate and restenosis at 8‐month follow‐up. These results confirmed the advantage of this specific technique to give complete coverage of the ostium of the side branch using two stents technique.