Guy R. Heyndrickx

A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease

BACKGROUND Balloon-expandable coronary-artery stents were developed to prevent coronary restenosis after coronary angioplasty. These devices hold coronary vessels open at sites that have been dilated. However, it is unknown whether stenting improves long-term angiographic and clinical outcomes as compared with standard balloon angioplasty. METHODS A total of 520 patients with stable angina and a single coronary-artery lesion were randomly assigned to either stent implantation (262 patients) or standard balloon angioplasty (258 patients). The primary clinical end points were death, the occurrence of a cerebrovascular accident, myocardial infarction, the need for coronary-artery bypass surgery, or a second percutaneous intervention involving the previously treated lesion, either at the time of the initial procedure or during the subsequent seven months. The primary angiographic end point was the minimal luminal diameter at follow-up, as determined by quantitative coronary angiography. RESULTS After exclusions, 52 patients in the stent group (20 percent) and 76 patients in the angioplasty group (30 percent) reached a primary clinical end point (relative risk, 0.68; 95 percent confidence interval, 0.50 to 0.92; P = 0.02). The difference in clinical-event rates was explained mainly by a reduced need for a second coronary angioplasty in the stent group (relative risk, 0.58; 95 percent confidence interval, 0.40 to 0.85; P = 0.005). The mean (+/- SD) minimal luminal diameters immediately after the procedure were 2.48 +/- 0.39 mm in the stent group and 2.05 +/- 0.33 mm in the angioplasty group; at follow-up, the diameters were 1.82 +/- 0.64 mm in the stent group and 1.73 +/- 0.55 mm in the angioplasty group (P = 0.09), which correspond to rates of restenosis (diameter of stenosis, > or = 50 percent) of 22 and 32 percent, respectively (P = 0.02). Peripheral vascular complications necessitating surgery, blood transfusion, or both were more frequent after stenting than after balloon angioplasty (13.5 vs. 3.1 percent, P < 0.001). The mean hospital stay was significantly longer in the stent group than in the angioplasty group (8.5 vs. 3.1 days, P < 0.001). CONCLUSIONS Over seven months of follow-up, the clinical and angiographic outcomes were better in patients who received a stent than in those who received standard coronary angioplasty. However, this benefit was achieved at the cost of a significantly higher risk of vascular complications at the access site and a longer hospital stay.

Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs.

The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods of regional myocardial ischemia, was studied in conscious dogs. Total left vemtricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure (dP/dt), and dP/dt/P. Regional LV function was assessed with measurements of regional segment length and velocity of shortening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 5- and 15-min periods on separate days. A 5-min occlusion depressed overall LV function transiently, but just before release of occlusion overall function had nearly returned to control. At this time regional function in the ischemic zone was still depressed to the point of absent shorteining or paradoxical motion during systole and was associated with marked ST segment elevation (+ 10 +/- 2.2 mV) at the site where function was measured. With release of occlusion and reperfusion the intramyocardial electrogram returned to normal within 1 min, and reactive hyperemia subsided by 5-10 min. In contrast to the rapid return to preocclusion levels for coronary flow and the electrogram, regional mechanical function remained depressed for over 3 h. A 15-min coronary occlusion resulted in an even more prolonged (greater than 6 h) derangement of function in the ischemic zone. Thus, brief periods of coronary occlusion result in prolonged impairement of regional myocardial function which could not have been predicted from the rapid return of the electrogram and coronary flow. These observations indicate that brief interruptions of coronary flow result either in a prolonged period of local ischemia or that alterations of mechanical induced by ischemia far outlast the repayment of the oxygen debt.

Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium.

BackgroundEven in the absence of a previous myocardial infarction, patients with coronary artery disease often present with chronic regional wall motion abnormalities that are reversible spontaneously or after coronary revascularization. In these patients, regional dysfunction has been proposed to result either from prolonged postischemic dysfunction (myocardial “stunning”) or from adaptation to chronic hypoperfusion (myocardial “hibernation”). This study examines which of these two mechanisms is responsible for the chronic regional dysfunction often detected in patients with angina and noninfarcted collateral-dependent myocardium. Methods and ResultsTwenty-six anginal patients (19 men; mean age, 60±9 years old) with chronic occlusion of a major coronary artery but without previous infarction were studied. Positron emission tomography was performed to measure absolute regional myocardial blood flow with13 N-ammonia at rest (N=26) and after intravenous dipyridamole (N=11). The kinetics of 18F-deoxyglucose and 11C-acetate were measured to calculate the rate of exogenous glucose uptake and the regional oxidative metabolism (n=15). Global and regional left ventricular function was evaluated by contrast ventriculography at baseline (n=26) and after revascularization (n=12). Transmural myocardial biopsies from the collateraldependent area were obtained in seven patients during bypass surgery and analyzed by optical and electron microscopy. According to resting regional wall motion, patients were separated into groups with and without dysfunction of the collateral-dependent segments. In patients with normal wall motion (n=9), regional myocardial blood flow, oxidative metabolism, and glucose uptake were similar among collateraldependent and remote segments. By contrast, in patients with regional dysfunction (n=17), collateraldependent segments had lower myocardial blood flow (77±25 versus 95±27 mL. min-1 100 g-1, p<0.001), smaller k values (slope of 11C clearance reflecting oxidative metabolism, 0.049±0.015 versus 0.068±0.020 min-1, p<0.001) and higher glucose uptake (relative 18F-deoxyglucose-to-flow ratio of 1.9 ± 1.6 versus 1.2±0.2, p<0.05) compared with remote segments. However, myocardial blood flow and k values were similar among collateral-dependent segments of patients with and without segmental dysfunction. After intravenous dipyridamole, collateral-dependent myocardial blood flow increased from 78±5 to 238±54 mL. min1 100 g-1 in three patients with normal wall motion and from 88±17 to only 112±44 mL min-1 100 g-1 in eight patients with regional dysfunction. There was a significant (R= -0.85, p<0.001) inverse correlation between wall motion abnormality and collateral flow reserve. Analysis of the tissue samples obtained at the time of bypass surgery showed profound structural changes in dysfunctioning collateral-dependent areas, including cellular swelling, loss of myofibrillar content, and accumulation of glycogen. Despite these alterations, the regional wall motion score improved significantly in the patients studied before and after revascularization (from 3.8 ± 1.3 to 0.8±0.9, p<0.005). ConclusionsIn a subgroup of patients with noninfarcted collateral-dependent myocardium, immature or insufficiently developed collaterals do not provide adequate flow reserve. Despite nearly normal resting flow and oxygen consumption, these collateral-dependent segments exhibit chronically depressed wall motion and demonstrale marked ultrastructural alterations on morphological analysis. We propose that these alterations result from repeated episodes of ischemia as opposed to chronic hypoperfusion and represent the flow, metabolic, and morphological correlates of myocardial “hibernation.”

Intracoronary Injection of CD133-Positive Enriched Bone Marrow Progenitor Cells Promotes Cardiac Recovery After Recent Myocardial Infarction Feasibility and Safety

Background—Bone marrow CD133-postive (CD133+) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133+ progenitor cells after intracoronary administration in patients with recent myocardial infarction. Methods and Results—Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133+ progenitor cells (12.6±2.2×106 cells) 11.6±1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0±2.6% to 52.1±3.5%, P<0.05), but only tended to increase in case-matched group 2 patients (from 44.3±3.1% to 48.6±3.6%, P=NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5±1.0% to 16.1±1.3%, P<0.05) but remained unchanged in group 2 patients (from 11.1±1.1% to 12.7±1.3%, P=NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0±4.1% to 22.5±4.1%, P<0.05) and no change in group 2 (from 25.0±3.0% to 22.6±4.1%, P=NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with 18fluorodeoxyglucose in the infarct-related territory increased from 51.2±2.6% to 57.5±3.5% (P<0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months. Conclusion—In patients with recent myocardial infarction, intracoronary administration of enriched CD133+ cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.

2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA).

Authors/Task Force Members: Steen Dalby Kristensen* (Chairperson) (Denmark), Juhani Knuuti* (Chairperson) (Finland), Antti Saraste (Finland), Stefan Anker (Germany), Hans Erik Bøtker (Denmark), Stefan De Hert (Belgium), Ian Ford (UK), Jose Ramón Gonzalez-Juanatey (Spain), Bulent Gorenek (Turkey), Guy Robert Heyndrickx (Belgium), Andreas Hoeft (Germany), Kurt Huber (Austria), Bernard Iung (France), Keld Per Kjeldsen (Denmark), Dan Longrois (France), Thomas F. Lüscher (Switzerland), Luc Pierard (Belgium), Stuart Pocock (UK), Susanna Price (UK), Marco Roffi (Switzerland), Per Anton Sirnes (Norway), Miguel Sousa-Uva (Portugal), Vasilis Voudris (Greece), Christian Funck-Brentano (France).

Simultaneous Coronary Pressure and Flow Velocity Measurements in Humans Feasibility, Reproducibility, and Hemodynamic Dependence of Coronary Flow Velocity Reserve, Hyperemic Flow Versus Pressure Slope Index, and Fractional Flow Reserve

BACKGROUND To assess coronary lesion severity in the catheterization laboratory, several guide wire-based methods have been proposed. The purpose of the present study was to compare the feasibility and the reproducibility of coronary flow velocity reserve (CFVR), instantaneous hyperemic diastolic velocity-pressure slope index (IHDVPS), and pressure-derived myocardial fractional flow reserve (FFRmyo). METHODS AND RESULTS From distal coronary pressure and flow velocity signals (0.014-in guide wires), CFVR, IHDVPS, and FFRmyo were computed in 15 stenoses (13 patients) under the four following pairs of conditions: (1) twice under baseline conditions; (2) during atrial pacing at 80 and 110 bpm; (3) before and during intravenous infusion of nitroprusside; and (4) before and during intravenous infusion of dobutamine. A total of 104 measurements were obtained. Both CFVR and FFRmyo could be calculated in all cases. IHDVPS could be calculated in only 79% of cases. The mean value of CFVR did not change between the two baseline measurements and during infusion of nitroprusside but decreased from 1.85 +/- 0.41 to 1.66 +/- 0.45 (P < .05) during atrial pacing and from 1.90 +/- 0.50 to 1.41 +/- 0.28 (P < .05) during dobutamine infusion. The mean values of IHDVPS and FFRmyo remained similar, whichever the changes in hemodynamic conditions. The coefficient of variation between two consecutive measurements was significantly lower for FFRmyo (4.2%) than for CFVR (17.7%) and for IHDVPS (24.7%). CONCLUSIONS CFVR is easy to measure but sensitive to hemodynamic changes. IHDVPS can be measured only in < 80% of cases and is highly variable even without changes in hemodynamic conditions. FFRmyo is easy to measure and almost independent of hemodynamic changes.

2014 ESC/ESA Guidelines on Non-cardiac Surgery: Cardiovascular Assessment and Management.

The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) are pleased to announce the publication of two new versions of Clinical Practice Guidelines (CPGs) on Perioperative Cardiovascular Evaluation from our respective organizations.1–3 These revisions were begun independently, dictated both by emerging, new information regarding the topic and the controversy regarding the legitimacy of data from previously published pivotal trials. Accordingly, the leadership of these international organizations recognized the importance of scientific collaboration and writing committee coordination for the benefit of the worldwide cardiology community. A joint statement was therefore posted in August 20134–6 to indicate that the respective CPGs were under revision and to provide some guidance regarding perioperative beta-blockade therapy in the interim. Since then, the members of both ESC and ACC/AHA guideline writing committees have reviewed the evidence thoroughly and systematically. The writing committees and the two supervisory task force groups decided to analyse separately the evidence about beta-blocker therapy used in the perioperative period and to develop specific treatment recommendations as a first step in the process of revision. After this independent work, the revised recommendations were shared between the two writing committees so that the rationales for any differences in recommendations could be articulated clearly. As a result of this process, we are confident that the evidence base has been objectively reviewed by two independent expert writing committees. The development of the two revised CPGs on perioperative cardiovascular care underscores the benefits of collaboration. Although the writing committees compiled and reviewed the evidence separately, they subsequently came together to validate their analyses, finding that they had both drawn on the same data and reached similar conclusions. Additionally, discussions are ongoing among the ACC, AHA, and ESC about sharing resources related to the systematic review of evidence. The potential advantages of more highly structured joint CPG initiatives are under active consideration. The CPGs on cardiovascular care in the perioperative period represent a fresh and objective review of old and new evidence in this important clinical arena. Features of the CPGs include the latest synthesis of the data on the use of beta-blockers in patients who have taken them chronically, considerations regarding selection of patients who are potential candidates to receive beta-blockers pre-operatively, and guidance regarding how to use this important and powerful class of drugs in the perioperative period. Clinicians will find the recommendations in these revised CPGs useful in their daily work and can be reassured that the recommendations have been vetted thoroughly by the most rigorous scientific process. Furthermore, the recommendations in both documents are fundamentally aligned, so that cardiovascular clinicians worldwide may deliver optimal, standardized care.

Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.

OBJECTIVES This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site.

Fractional Flow Reserve in Patients With Prior Myocardial Infarction

Background—Fractional flow reserve (FFR), an index of coronary stenosis severity, can be calculated from the ratio of hyperemic distal to proximal coronary pressure. An FFR value of 0.75 can distinguish patients with normal and abnormal noninvasive stress testing in case of normal left ventricular function. The present study aimed at investigating the value of FFR in patients with a prior myocardial infarction. Methods and Results—In 57 patients who had sustained a myocardial infarction ≥6 days earlier, myocardial perfusion single photon emission scintigraphy (SPECT) imaging and FFR were obtained before and after angioplasty. The sensitivity and specificity of the 0.75 value of FFR to detect flow maldistribution at SPECT imaging were 82% and 87%. The concordance between the FFR and SPECT imaging was 85% (P <0.001). When only truly positive and truly negative SPECT imaging were considered, the corresponding values were 87%, 100%, and 94% (P <0.001). Patients with positive SPECT imaging before angioplasty had a significantly lower FFR than patients with negative SPECT imaging (0.52±0.18 versus 0.67±0.16, P =0.0079) but a significantly higher left ventricular ejection fraction (63±10% versus 52±10%, P =0.0009) despite a similar degree of diameter stenosis (67±13% versus 68±16%, P =NS). A significant inverse correlation was found between LVEF and FFR (R =0.29, P =0.049). Conclusions—The present data indicate (1) that the 0.75 cutoff value of FFR to distinguish patients with positive from patients with negative SPECT imaging is valid after a myocardial infarction and (2) that for a similar degree of stenosis, the value of FFR depends on the mass of viable myocardium.

Relation Between Myocardial Fractional Flow Reserve Calculated From Coronary Pressure Measurements and Exercise-Induced Myocardial Ischemia

BACKGROUND Myocardial fractional flow reserve (FFRmyo) is a functional index of stenosis severity that can be derived from intracoronary pressure measurements performed during maximal vasodilatation. It is defined as the maximal myocardial perfusion during hyperemia in the presence of a stenosis in the epicardial artery expressed as a fraction of its normal maximal expected value. To determine threshold values of FFRmyo, of hyperemic translesional pressure gradient (delta P(max)), and of resting translesional pressure gradient (delta P(rest)) that are uniformly associated with exercise-induced ischemia, we studied the relation between these pressure-derived indexes and the results of exercise ECG. METHODS AND RESULTS We studied 60 patients with an isolated lesion in one major epicardial coronary artery, normal left ventricular function, and no left ventricular hypertrophy. Maximal exercise ECG (off anti-ischemic medication) was performed within 6 hours before catheterization. Intracoronary pressure measurements were taken at rest and during hyperemia with a pressure monitoring guide wire. ST-segment depressions at peak exercise (considered abnormal when > or = 0.1 mV) were compared with FFRmyo, delta P(max), and delta P(rest). Thirty-seven patients had an abnormal and 23 patients a normal exercise ECG. A significant linear correlation was found between the magnitude of ST-segment depressions and both FFRmyo and delta P(max) (r = -.75, SEE = 0.53; r = .71, SEE = 0.56). A weaker correlation was noted between ST-segment depressions and delta P(rest) (r = .53, SEE = 0.67). Sensitivity and specificity curves were constructed for the prediction of an abnormal exercise ECG for the three pressure-derived indexes. The values that most accurately predicted an abnormal exercise ECG were 66% for FFRmyo, 31 mm Hg for delta P(max), and 12 mm Hg for delta P(rest). No patient with a FFRmyo value > 72% showed an abnormal exercise ECG. In addition, receiver operating characteristic curves demonstrated a greater accuracy of FFRmyo and of delta P(max) than of delta P(rest) for predicting the results of the exercise ECG. CONCLUSIONS In the present study, cutoff values of FFRmyo and translesional pressure gradients are established from the relation between intracoronary pressure-derived indexes and ECG signs of myocardial ischemia during maximal exercise. These values can be helpful for clinical decision making in cases with dubious angiographic results. Furthermore, our data support the concept that stenosis physiology is better reflected by hyperemic than by basal measurements.