Walter Desmet

Apical ballooning of the left ventricle: first series in white patients

Background: A cardiac syndrome of “apical ballooning” was recently described, consisting of an acute onset of transient extensive akinesia of the apical and mid portions of the left ventricle, without significant stenosis on the coronary angiogram, accompanied by chest symptoms, ECG changes, and a limited release of cardiac markers disproportionate to the extent of akinesia. Until now, this syndrome has been reported only in Japanese patients. Objective: To describe 13 white patients who presented with this syndrome over the previous four years. Results: All but one of the patients were women with a mean age of 62 years. Eight of them presented with chest pain, of whom six had cardiogenic shock. In nine patients a triggering factor was identified: emotional stress in three, trauma in one, pneumonia in one, asthma crisis in one, exercise in two, and cerebrovascular accident in one. In all patients left ventriculography showed very extensive apical akinesia (“apical ballooning”) in the absence of a significant coronary artery stenosis, not corresponding with the perfusion territory of a single epicardial coronary artery. Mean maximal creatine kinase MB and troponin rise were 27.4 μg/l (range 5.2–115.7 μg/l, median 16.6 μg/l) and 18.7 μg/l (range 2.0–97.6 μg/l, median 14.5 μg/l), respectively. Six patients were treated with intra-aortic balloon counterpulsation. One patient died of multiple organ failure. On necropsy, no myocardial infarction was found. In the 12 survivors, left ventricular systolic function recovered completely within three weeks. Conclusions: This is the first series of “apical ballooning” to be reported in white patients. Despite dramatic initial presentation, left ventricle function recovered completely within three weeks in the survivors.

ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting

BACKGROUND In patients receiving aspirin, the optimal duration of clopidogrel therapy after drug-eluting stent (DES) implantation remains unclear. METHODS This multicentre, randomized, double-blind, placebo-controlled trial tested the hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES implantation, patients on clopidogrel were randomly assigned to either a 6-month period of placebo or an additional 6-month period of clopidogrel. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction major bleeding at 9 months after randomization. RESULTS Owing to slow recruitment and low event rates, the trial was stopped prematurely after enrolment of 4005 of 6000 planned patients. Of 4000 patients included in the final analysis, 1997 received 6 months of clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29 patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%) assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95% confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6 months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21-2.98, P = 0.74. CONCLUSIONS In the present trial, characterized by low event rates, we did not observe a significant difference in net clinical outcome between 6 and 12 months of clopidogrel therapy after DES implantation. However, the results of the trial must be considered in view of its premature termination and lower than expected event rates. The trial is registered with ClinicalTrials.gov, Identifier: NCT00661206.

Impaired Myocardial Tissue Perfusion Early After Successful Thrombolysis Impact on Myocardial Flow, Metabolism, and Function at Late Follow-up

BACKGROUND Impaired tissue reperfusion after successful recanalization of an epicardial coronary artery has been documented both in animals and in patients with acute myocardial infarction. Whether this phenomenon can be demonstrated with positron emission tomography (PET) and whether it has an effect on late recovery of flow, metabolism, and function are unknown. METHODS AND RESULTS Thirty patients with an acute myocardial infarction and TIMI flow grade 3 of the infarcted vessel at 90 minutes after thrombolytic therapy were studied. Within 24 hours after thrombolysis, at 5 days and at 3 months, myocardial blood flow was measured with 13NH3. 18FDG uptake was measured at 5 days. Radionuclide left ventricular angiograms were acquired at 5 days and at 3 months. In 11 patients (37%), regional myocardial flow was severely impaired (< 50% of normally perfused myocardium) despite successful thrombolysis. No recovery of left ventricular function occurred in any of these patients at 3 months. In 12 patients (40%), intermediate flows (50% to 75% of normal) were found, with functional improvement after angioplasty only in regions with a PET mismatch. Seven patients (23%) had high flow values early after successful thrombolysis (> 75% of normal) and showed preserved regional contractile function at 3 months. CONCLUSIONS This study is the first demonstration with PET of impaired myocardial tissue perfusion in patients with an acute myocardial infarction after successful thrombolysis. Functional recovery of the reperfused myocardium is observed only when adequate tissue flow is restored. PET may be helpful in selecting patients in whom additional revascularization can improve recovery of left ventricular function.

Quantification of Myocardial Area at Risk With T2-Weighted CMR Comparison With Contrast-Enhanced CMR and Coronary Angiography

OBJECTIVES We sought to quantify the myocardium at risk in reperfused acute myocardial infarction (AMI) in man with T2-weighted (T2W) cardiac magnetic resonance (CMR). BACKGROUND The myocardial area at risk (AAR) is defined as the myocardial tissue within the perfusion bed distally to the culprit lesion of the infarct-related coronary artery. T2W CMR is appealing to retrospectively determine the myocardial AAR after reperfused AMI. Data on the utility of this technique in humans are limited. METHODS One hundred eight patients with successfully reperfused ST-segment elevation AMI were studied between 1 and 20 days after percutaneous coronary intervention (PCI). We compared the volume of hyperintense myocardium on T2W CMR with the myocardial AAR determined by contrast-enhanced CMR with infarct endocardial surface length (ESL) and AAR estimated by conventional coronary angiography with the BARI (Bypass Angioplasty Revascularization Investigation) risk score. RESULTS The volume of hyperintense myocardium on T2W CMR (mean 32 +/- 16%, range 3% to 67%) was consistently larger than the volume of myocardial infarction measured with contrast-enhanced images (mean 17 +/- 12%, range 0% to 55%) (p < 0.001). Myocardial salvage ranged from -4% to 45% of the left ventricular myocardium (mean 14 +/- 10%). The AAR determined by T2W CMR compared favorably with the infarct ESL (r = 0.77) with contrast-enhanced CMR, and there was moderate correlation between the BARI angiographic risk score and infarct ESL (r = 0.42). The time between PCI and CMR did not cause a significant difference in the volume of T2W hyperintense myocardium (r = 0.11, p = 0.27) or the calculated volume of salvaged myocardium (r = 0.12, p = 0.23). CONCLUSIONS T2W CMR performed early after successfully reperfused AMI in humans enables retrospective quantification of the myocardial AAR and salvaged myocardium.

Functional Recovery of Subepicardial Myocardial Tissue in Transmural Myocardial Infarction After Successful Reperfusion: An Important Contribution to the Improvement of Regional and Global Left Ventricular Function

BACKGROUND The transmural extent of myocardial necrosis after an acute coronary artery occlusion can vary considerably. The contribution of residual subepicardial viable myocardium to global left ventricular function is largely unknown. METHODS AND RESULTS We studied 12 patients with single-vessel disease 1 week after successful reperfusion of a first transmural anterior myocardial infarction (MI). With PET, myocardial blood flow (MBF) and glucose metabolism were measured regionally, and the viability was graded as normal, mismatch, or match with severely (<50% of normal) or intermediately (50% to 80% of normal) impaired MBF. Magnetic resonance tagging was used to regionally quantify fiber strains, wall thickening, and ejection fraction in patients 1 week and 3 months after the MI and in age-matched healthy volunteers. From 1 week to 3 months, subepicardial fiber shortening improved significantly in the match region (MBF <50%, -5.1+/-7.0% to -9.9+/-8. 7%; MBF of 50% to 80%, -7.1+/-7.6% to -14.9+/-7.9%). This was associated with an improvement in regional ejection fraction in the infarcted myocardium (29.6+/-21.8% to 43.5+/-15.5%, P<0.0001) and in normal regions (54.3+/-15.1% to 56.5+/-13.1%, P=0.013), contributing to an increase in global ejection fraction from 44.2+/-22.2% to 49. 3+/-17.9% (P<0.0001). CONCLUSIONS Functional recovery of viable subepicardial regions is a mechanism of late improvement in regional and global ejection fraction after a so-called transmural MI.

Intravascular ultrasound versus angiography for measurement of luminal diameters in normal and diseased coronary arteries

Quantitation of coronary luminal diameter with a 20 MHz mechanically rotating intravascular ultrasound (IVUS) catheter was compared with orthogonal-view cineangiography by use of a semiautomated edge-detection algorithm in 48 patients undergoing coronary angioplasty. Quantitative comparison of 196 matched segments was attempted, but in only 174 (88.8%) was a direct comparison of the two techniques possible. In angiographically normal coronary arteries (46 segments) the correlation between the values obtained by quantitative coronary angiography (QCA) and those achieved by IVUS was excellent (r = 0.92, p < 0.0001). For mild stenoses (80 segments) the correlation coefficient was only fair (r = 0.467, p < 0.001). After percutaneous transluminal coronary angioplasty the correlation coefficient between IVUS and QCA data (48 segments) was very weak (r = 0.282, p < 0.05). In conclusion, coronary IVUS is feasible and safe and even for a limited range of coronary arterial narrowing, significant correlations between IVUS and QCA measurements of minimal lumen diameter were found. They were excellent in normal coronary arteries, moderate in mildly diseased arteries, and weak after balloon angioplasty.

High dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction

AIMS Previous studies have suggested that intravenous administration of adenosine improves myocardial reperfusion and reduces infarct size in ST-elevation myocardial infarction (STEMI) patients. Intracoronary administration of adenosine has shown conflicting results. METHODS AND RESULTS In a prospective, single-centre, double-blind, placebo-controlled clinical study, we assessed whether selective intracoronary administration of adenosine distal to the occlusion site immediately before initial balloon inflation results in myocardial salvage and decreased microvascular obstruction (MVO) as assessed with cardiac magnetic resonance imaging (MRI). Using a combination of T(2)-weighted and contrast-enhanced sequences, myocardial salvage index (MSI) was defined as the percentage of the area at risk that did not become necrotic. We randomized 112 patients presenting with STEMI within 12 h from symptom onset to selective intracoronary administration of adenosine 4 mg or matching placebo. In 100/110 (91%) patients receiving study drug, MRI was performed on Days 2-3. No significant difference in MSI was found between adenosine- and placebo-treated patients: 41.3% (20.8, 66.7) vs. 47.8% (39.8, 60.9) [median (Q1, Q3)] (P = 0.52). The extent of MVO was comparable in both groups, with a trend favouring the placebo group: 2.4 g (0.0, 6.8) vs. 5.9 g (0.0, 12.8) after adenosine (P = 0.07). TIMI flow grade, TIMI frame count, myocardial blush grade, and ST-segment resolution after primary percutaneous coronary intervention were similar between groups. After 4 months, infarct size was similar in both treatment groups. CONCLUSION We found no evidence that selective high-dose intracoronary administration of adenosine distal to the occlusion site of the culprit lesion in STEMI patients results in incremental myocardial salvage or a decrease in microvascular obstruction.

Effectiveness and Safety of Sirolimus-Eluting Stents in the Treatment of Restenosis After Coronary Stent Placement

Background—In-stent restenosis is notoriously difficult to treat by repeat catheter intervention because of its propensity for aggressive recurrent neointimal formation. This study sought to assess the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis. Methods and Results—The study was designed as a prospective multicenter registry. We included 162 patients with in-stent restenosis of a native coronary artery who had a clinical indication for repeat intervention. Patients were scheduled for follow-up angiography at 6 months. The primary end point was in-lesion late loss. Follow-up angiography was performed in 155 patients. We obtained an in-lesion late loss of 0.08±0.49 mm and a binary restenosis rate of 9.7% (15/155), which prompted reintervention in 7.4% (12/162) at 9 months. The 9-month rate of death was 1.2% (2/162) and that of nonfatal myocardial infarction was 1.2% (2/162). Conclusions—Sirolimus-eluting stents were highly efficacious and safe in the treatment of in-stent restenosis. Our study provides rationale for the use of sirolimus-eluting stents in the treatment of in-stent restenosis.

Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade Compared With Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Intervention

A. Michael Lincoff, MD John A. Bittl, MD Robert A. Harrington, MD Frederick Feit, MD Neal S. Kleiman, MD J. Daniel Jackman, MD Ian J. Sarembock, MD David J. Cohen, MD Douglas Spriggs, MD Ramin Ebrahimi, MD Gadi Keren, MD Jeffrey Carr, MD Eric A. Cohen, MD Amadeo Betriu, MD Walter Desmet, MD Dean J. Kereiakes, MD Wolfgang Rutsch, MD Robert G. Wilcox, MD Pim J. de Feyter, MD Alec Vahanian, MD Eric J. Topol, MD for the REPLACE-2 Investigators

Strain Echocardiography Improves Risk Prediction of Ventricular Arrhythmias After Myocardial Infarction

OBJECTIVES The aim of this study was to test the hypothesis that strain echocardiography might improve arrhythmic risk stratification in patients after myocardial infarction (MI). BACKGROUND Prediction of ventricular arrhythmias after MI is challenging. Left ventricular ejection fraction (LVEF) <35% is the main parameter for selecting patients for implantable cardioverter-defibrillator therapy. METHODS In this prospective, multicenter study, 569 patients >40 days after acute MI were included, 268 of whom had ST-segment elevation MIs and 301 non-ST-segment elevation MIs. By echocardiography, global strain was assessed as average peak longitudinal systolic strain from 16 left ventricular segments. Time from the electrocardiographic R-wave to peak negative strain was assessed in each segment. Mechanical dispersion was defined as the standard deviation from these 16 time intervals, reflecting contraction heterogeneity. RESULTS Ventricular arrhythmias, defined as sustained ventricular tachycardia or sudden death during a median 30 months (interquartile range: 18 months) of follow-up, occurred in 15 patients (3%). LVEFs were reduced (48 ± 17% vs. 55 ± 11%, p < 0.01), global strain was markedly reduced (-14.8 ± 4.7% vs. -18.2 ± 3.7%, p = 0.001), and mechanical dispersion was increased (63 ± 25 ms vs. 42 ± 17 ms, p < 0.001) in patients with arrhythmias compared with those without. Mechanical dispersion was an independent predictor of arrhythmic events (per 10-ms increase, hazard ratio: 1.7; 95% confidence interval: 1.2 to 2.5; p < 0.01). Mechanical dispersion and global strain were markers of arrhythmias in patients with non-ST-segment elevation MIs (p < 0.05 for both) and in those with LVEFs >35% (p < 0.05 for both), whereas LVEF was not (p = 0.33). A combination of mechanical dispersion and global strain showed the best positive predictive value for arrhythmic events (21%; 95% confidence interval: 6% to 46%). CONCLUSIONS Mechanical dispersion by strain echocardiography predicted arrhythmic events independently of LVEF in this prospective, multicenter study of patients after MI. A combination of mechanical dispersion and global strain may improve the selection of patients after MI for implantable cardioverter-defibrillator therapy, particularly in patients with LVEFs >35% who did not fulfill current implantable cardioverter-defibrillator indications.