Pascal Motreff

Cyclosporine before PCI in Patients with Acute Myocardial Infarction

BACKGROUND Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Fractal geometry of arterial coronary bifurcations: a quantitative coronary angiography and intravascular ultrasound analysis.

AIMS Coronary artery bifurcations present a harmonious asymmetric geometry that is fractal in nature. Interventional treatment of bifurcation lesions is a major technical issue. The present study is aimed at a precise quantification of this geometry in the hope of deriving a formulation that would be simple to calculate. METHODS AND RESULTS Forty seven patients with strictly normal coronarographic results obtained ahead of valve replacement were enrolled, and 27 of these underwent IVUS examination to confirm that their arteries were indeed normal. Three reference diameters were measured: those of the mother vessel (Dm) and of either daughter vessel (Dd1, Dd2). One hundred and seventy-three bifurcations were thus subjected to quantitative analysis. The mean diameter of the mother vessels was 3.33+/-0.94 mm, of the major daughter vessels 2.70+/-0.77 mm, and of the minor daughter vessels 2.23+/-0.68 mm. The ratio R=Dm/(Dd1+Dd2) of mother-vessel diameter to the sum of the two daughter-vessel diameters was 3.39/(2.708+2.236)=0.678. This ratio held at all levels of bifurcation: i.e., whatever diameter the mother vessel. CONCLUSION The study confirmed the fractal nature of the geometry of the epicardial coronary artery tree, and gave a simple and accurate fractal ratio between the diameters of the mother and two daughter vessels such that Dm=0.678 (Dd1+Dd2). This makes it easy to calculate the precise diameter of any of the three vessels when those of the other two are known.

OCT-Based Diagnosis and Management of STEMI Associated With Intact Fibrous Cap

In autopsy studies, at least 25% of thrombotic coronary occlusions are caused by plaque erosion in which thrombus often overlies atherosclerotic plaque without evident disruption of the fibrous cap. We performed optical coherence tomography imaging after aspiration thrombectomy and identified plaque erosion as the cause in 31 patients presenting with ST-segment elevation myocardial infarction. Plaque erosion was identified when the fibrous cap of the culprit lesion was intact. Based on clinical criteria, 40% of patients with subcritically occlusive plaque were treated with dual antiplatelet therapy without percutaneous revascularization (group 1), and the remaining 60% of patients underwent angioplasty and stenting (group 2). At a median follow-up of 753 days, all patients were asymptomatic, regardless of stent implantation. These observations support an alternative treatment strategy for patients with acute coronary events and optical coherence tomography-verified intact fibrous cap (or plaque erosion), where nonobstructive lesions might be managed without stenting.

Mechanisms of stent thrombosis analysed by optical coherence tomography: insights from the national PESTO French registry

AIMS Angiography has limited value for identifying the causes of stent thrombosis (ST). We studied a large cohort of patients by optical coherence tomography (OCT) to explore ST characteristics and mechanisms. METHODS AND RESULTS A prospective multicentre registry was screened for patients with confirmed ST. Optical coherence tomography was performed after initial intervention to the culprit lesion (in 69% of cases in a deferred procedure). Stent thrombosis was classified as acute (AST), sub-acute (SAST), late (LST), and very late (VLST). Optical coherence tomography records were analysed in a central core lab. The analysis included 120 subjects aged 61.7 [51.4-70.7]; 89% male. Very late ST was the clinical presentation in 75%, LST in 6%, SAST in 15%, and AST in 4% of patients. Bare metal stents (BMS) were used in 39%, drug-eluting stents (DES) in 59% and bioresorbable vascular scaffolds in 2% of the cases. Optical coherence tomography identified an underlying morphological abnormality in 97% of cases, including struts malapposition (34%), neoatherosclerotic lesions (22%), major stent underexpansion (11%), coronary evagination (8%), isolated uncovered struts (8%), edge-related disease progression (8%), and neointimal hyperplasia (4%). Ruptured neoatherosclerotic lesions were more frequent with BMS than with DES (36 vs. 14%, P = 0.005), whereas coronary evaginations were more frequent with DES than with BMS (12 vs. 2%, P = 0.04). LST + VLST were mainly related to malapposition (31%) and neoatherosclerosis (28%), while prominent mechanisms for AST + SAST were malapposition (48%) and underexpansion (26%). CONCLUSION In patients with confirmed ST, OCT imaging identified an underlying morphological abnormality in 97% of cases.

Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients with Non-ST-Elevation Acute Coronary Syndrome: Results of the Multicenter, Randomized DOCTORS Study (Does Optical Coherence Tomography Optimize Results of Stenting).

Background: No randomized study has investigated the value of optical coherence tomography (OCT) in optimizing the results of percutaneous coronary intervention (PCI) for non–ST-segment elevation acute coronary syndromes. Methods: We conducted a multicenter, randomized study involving 240 patients with non–ST-segment elevation acute coronary syndromes to compare OCT-guided PCI (use of OCT pre- and post-PCI; OCT-guided group) to fluoroscopy-guided PCI (angiography-guided group). The primary end point was the functional result of PCI assessed by the measure of post PCI fractional flow reserve. Secondary end points included procedural complications and type 4a periprocedural myocardial infarction. Safety was assessed by the rate of acute kidney injury. Results: OCT use led to a change in procedural strategy in 50% of the patients in the OCT-guided group. The primary end point was improved in the OCT-guided group, with a significantly higher fractional flow reserve value (0.94±0.04 versus 0.92±0.05, P=0.005) compared with the angiography-guided group. There was no significant difference in the rate of type 4a myocardial infarction (33% in the OCT-group versus 40% in the angiography-guided group, P=0.28). The rates of procedural complications (5.8%) and acute kidney injury (1.6%) were identical in each group despite longer procedure time and use of more contrast medium in the OCT-guided group. Post-PCI OCT revealed stent underexpansion in 42% of patients, stent malapposition in 32%, incomplete lesion coverage in 20%, and edge dissection in 37.5%. This led to the more frequent use of poststent overdilation in the OCT-guided group versus the angiography-guided group (43% versus 12.5%, P<0.0001) with lower residual stenosis (7.0±4.3% versus 8.7±6.3%, P=0.01). Conclusions: In patients with non–ST-segment elevation acute coronary syndromes, OCT-guided PCI is associated with higher postprocedure fractional flow reserve than PCI guided by angiography alone. OCT did not increase periprocedural complications, type 4a myocardial infarction, or acute kidney injury. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01743274.

Management of Spontaneous Coronary Artery Dissection: Review of the Literature and Discussion Based on a Series of 12 Young Women with Acute Coronary Syndrome

Spontaneous coronary artery dissection (SCAD) is a rare pathology, principally affecting young women free of atheroma risk factors. Its physiopathology remains little understood, and the prognosis for such acute coronary syndromes is poor, as they occur suddenly. Management is often difficult, and no guidelines exist. The present single-center retrospective study concerns 12 cases of SCAD occurring between 2001 and 2008 in female patients under the age of 60. Eleven patients survived, with a favorable long-term evolution. Only 2 had conservative medical therapy, the other 10 undergoing percutaneous coronary intervention (2 procedures involving a coronary artery bypass graft). On the basis of this series and data from the literature, we suggest a strategy to improve the often dire prognosis of SCAD. Emergency angiography to confirm diagnosis is essential. Treatment should be guided by the extent of the lesions, the myocardial ischemia and the hemodynamic status. Conservative medical therapy is a reasonable approach in the case of distal dissection or conserved coronary flow. Percutaneous coronary intervention is feasible in the acute phase to restore coronary perfusion and hemodynamic stability. Surgery – emergency bypass or assisted circulation – should be restricted to cases where percutaneous coronary intervention has failed or is impossible.

Comparison of INR stability between self-monitoring and standard laboratory method: Preliminary results of a prospective study in 67 mechanical heart valve patients

INTRODUCTION Thromboembolic accidents and haemorrhage are the main complications observed during long-term follow-up of mechanical heart valve patients. Several suggestions for improving anticoagulation quality have been made, including international normalised ratio (INR) self-monitoring. OBJECTIVES We report the preliminary results of a single-centre, open, randomised study (scheduled population of 200 patients), which compares monthly laboratory monitoring (group A) versus weekly self-monitoring of INR (group B). The primary aim is INR stability improvement within the target range, and the secondary aim is adverse events reduction. PATIENTS AND METHODS Between May 2004 and June 2005, 67 patients with an average age of 56.6 years (+/-9.6), were enrolled in the study (group A: 34 patients, group B: 33 patients). The mean follow-up was 47 weeks (+/-11.5). The two groups differed only in the sex ratio (44.1 and 21.2% of women in groups A and B respectively, p=0.0459). Mechanical heart valves were aortic in 73% of patients, mitral in 13.5%, and multiple in 13.5%. Sixty-five patients (97%) were treated with fluindione, the others with acenocoumarol. The intraclass correlation coefficient between the self- and laboratory-monitored INR was 0.75. RESULTS The time spent in the INR target range (group A: 53+/-19%, group B: 57+/--19%, p=0.45) and the time spent in the INR therapeutic range, between 2 and 4.5, (group A: 86+/-14%, group B: 91+/-7%, p=0.07) are longer in group B, but not significantly so. For patients outside the range, the absolute mean deviation of INR from the target or therapeutic range (range standardized between 0 and 100) is lower for the self-monitoring group (41.1+/-39.3 and 11.27+/-11.2) than for the control group (62.4+/-72.6 and 39.2+/-52.8). This difference is significant (p=0.0004 and p=0.0005). Eighteen adverse events were reported: 17 haemorrhages, 13 in group A (9 mild, 4 serious) and four in group B (all mild), and one sudden death in group B, two days after the patients discharge. No thromboembolic events were reported. Six patients (8.8 %), 3 in each group, dropped out of the study. CONCLUSION This first study evaluating INR self-monitoring in France shows that this method leads to better stability of the INR within the target range. On the basis of these preliminary data, this appears to be related to a decrease in serious haemorrhages (11.8% serious haemorrhage cases in group A versus 0% in group B, p=0.06, NS).

Invasive management without stents in selected acute coronary syndrome patients with a large thrombus burden: a prospective study of optical coherence tomography guided treatment decisions

AIMS To assess whether a strategy of invasive management without stents in selected acute coronary syndrome (ACS) patients with a large thrombus burden (LTB) might be feasible and safe. METHODS AND RESULTS We performed a prospective non-randomised observational cohort study of invasive treatment decisions guided by optical coherence tomography (OCT) in selected ACS patients with LTB. Among 852 ACS patients who had undergone invasive coronary angiography, 101 (11.8%) patients with large thrombus burden on initial angiography underwent thrombectomy to restore TIMI 3 flow without stenting. All of these patients then had repeat angiography with OCT (days 0-2 [Group 1], days 3-6 [Group 2] or days 7-30 [Group 3]). No adverse events occurred between the initial and second angiograms. Residual thrombus was detected in 68% of patients with OCT (respectively, 94%, 79% and 32% in Group 1, Group 2 and Group 3), and 20% of cases with angiography. Plaque rupture was detected by OCT in 65% of cases. Minimal lumen area was 2.81 mm2, 3.40 mm2 and 4.89 mm2 in Group 1, Group 2 and Group 3, respectively. Sixty-two percent of patients were stented (respectively, 76%, 61% and 50%). During a minimum follow-up period of 12 months in all patients, one non-fatal MI occurred and one PCI was performed for angina. CONCLUSIONS Medical management without stents is safe and feasible in selected ACS patients with LTB. OCT revealed culprit lesion characteristics that were not disclosed by angiography and facilitated treatment decisions.

In Vivo Supervised Analysis of Stent Reendothelialization From Optical Coherence Tomography

The aim of this study is to interactively assess reendothelialization of stents at an accuracy of down to a few micrometer by analyzing endovascular optical coherence tomography (OCT) sequences. Vessel wall and stent struts are automatically detected by using morphological, gradient, and symmetry operators coupled with active contour models; alerts are issued to ask for user supervision over some extreme irregular geometries caused by thrombotic lesions or dissections. A complete distance map is then computed from sparse distances measured between wall and struts. Missing values are interpolated by thin-plate spline (TPS) functions. Accuracy and robustness are increased by taking into account the inhomogeneity of data points and integrating in the same framework orthogonalized forward selection of support points, optimal selection of regularization parameters by generalized cross-validation, and rejection of detection outliers. Validation is performed on simulated data, phantom acquisitions and 11 typical in vivo OCT sequences. The comparison against manual expert measurements demonstrates a bias of the order of OCT resolution (less than 10 ¿m) and a standard deviation of the order of the strut width (less than 150 ¿m ).

Early Aldosterone Blockade in Acute Myocardial Infarction: The ALBATROSS Randomized Clinical Trial.

BACKGROUND Mineralocorticoid receptor antagonists (MRA) improve outcome in the setting of post-myocardial infarction (MI) heart failure (HF). OBJECTIVES The study sought to assess the benefit of an early MRA regimen in acute MI irrespective of the presence of HF or left ventricular (LV) dysfunction. METHODS We randomized 1,603 patients to receive an MRA regimen with a single intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) for 6 months in addition to standard therapy or standard therapy alone. The primary outcome of the study was the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF at 6-month follow-up. Key secondary/safety outcomes included death and other individual components of the primary outcome and rates of hyperkalemia at 6 months. RESULTS The primary outcome occurred in 95 (11.8%) and 98 (12.2%) patients in the treatment and control groups, respectively (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.73 to 1.28). Death occurred in 11 (1.4%) and 17 (2.1%) patients in the treatment and control groups, respectively (HR: 0.65; 95% CI: 0.30 to 1.38). In a non-pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 [0.5%] vs. 15 [2.4%]; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non-ST-segment elevation MI (p for interaction = 0.01). Hyperkalemia >5.5 mmol/l(-1) occurred in 3% and 0.2% of patients in the treatment and standard therapy groups, respectively (p < 0.0001). CONCLUSIONS The study failed to show the benefit of early MRA use in addition to standard therapy in patients admitted for MI. (Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up; NCT01059136).