Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.

RATIONALE: Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors. OBJECTIVES: We hypothesized that the extent of the vascular cell damage measured by circulating microparticles could be related to the severity of pulmonary arterial hypertension (PAH). METHODS: Circulating biomarkers of vascular damage and cell activation were measured in blood samples from 20 patients with PAH. Samples were withdrawn from occluded pulmonary artery and jugular vein. Peripheral venous blood samples were obtained in 23 control subjects. The microparticle procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin was determined. MEASUREMENTS AND MAIN RESULTS: Soluble vascular cellular adhesion molecule-1 and proinflammatory markers, such as monocyte chemoattractant protein-1 and highly specific C-reactive protein, were elevated in patients with PAH compared with control subjects. Microparticles bearing active tissue factor and CD105 (endoglin) were also elevated in patients with PAH compared with control subjects (29 +/- 13 vs. 16 +/- 6 fmol/L, P < 0.001, and 1.10 +/- 0.46 vs. 0.49 +/- 0.33 nmol/L phosphatidylserine equivalent, P < 0.001, respectively). A further increase in endothelium-derived CD105 microparticles was observed in pulmonary arterial blood compared with venous blood in patients with PAH (1.73 +/- 0.77, P = 0.038). Microparticles bearing active tissue factor were at a higher level in patients in functional class III and IV and who were walking fewer than 380 m with the six-minute-walk test. CONCLUSIONS: Circulating markers of endothelium damage, proinflammatory markers, and cell stimulation estimated with circulating microparticles appear to be valuable tools in determining the severity of PAH.

Acute Appendicitis as an Unexpected Cause of Inverted Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TTC), also known as transient left ventricular ballooning syndrome, is a stress-induced-cardiomyopathy. It is precipitated by emotional or physical stress and is characterized by normal coronary arteries and transient regional wall motion abnormalities. Variants of TTC include apical ballooning syndrome and, less commonly, mid, basal, and local variants. New onset heart failure or acute coronary syndromes are a common presentation of TTC. Arrhythmias such as VT, VF, and torsade de pointes have also been reported. We present here a 42-year-old man with an inverted Takotsubo variant with pulmonary edema and transient accelerated idioventricular rhythm. He was initially admitted in the Emergency Department for acute and non-complicated appendicitis. Coronary angiogram showed normal coronary arteries and left ventriculography revealed a reverse variant of TTC. The patient had completely recovered. Myocarditis was ruled out by cardiac magnetic resonance imaging.

Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus.

During myocardial infarction (MI), platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP were described in diabetes mellitus (DM), and could be of particular significance in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM) patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon thrombin cleavage. Variations were compared to values measured in healthy volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and quantified by prothrombinase assay. Their cellular origin was assessed. With respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of platelet-derived MP and the correlation between procoagulant MP and sGPV, testify to the central role of thrombin-activated platelets during MI in both DM and NDM subsets. The release of platelet and endothelial cell-derived MP persisted at D6 and was more important in DM, the associated prothrombotic risk being also reflected by higher levels of sGPV. The endothelial damage revealed by endothelial-derived MP was twice that observed in NDM patients. In DM patients presenting cardio-vascular events at 6 month follow-up, MP levels were significantly higher at D1 after MI than in those without complication (24.9 +/- 4.8 vs. 12.3 +/- 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP.

Impact of manual thrombectomy on myocardial reperfusion as assessed by ST-segment resolution in STEMI patients treated by primary PCI.

BACKGROUND: In STEMI patients treated by primary PCI, damage of the microvascular circulation caused by distal embolization of thrombotic material affects the quality of myocardial reperfusion. Important controversies remain concerning the usefulness of the manual thrombectomy to improve myocardial perfusion. The aim of this study is to evaluate the impact of manual thrombectomy on ST resolution as a surrogate of reperfusion extent. METHODS: Two hundred and thirty-nine consecutive STEMI patients with an <12 hours onset of symptoms, were enrolled in an observational registry. Patients were divided into two cohorts according to the reperfusion strategy: manual thrombectomy before primary PCI (n=102) or conventional-PCI (n=137). The primary endpoint was the post procedural frequency of complete (>70%) resolution of ST segment elevation. RESULTS: A complete resolution of ST segment elevation occurred in 51.4% of patients in the thrombectomy group and in 35,6% of those in the conventional-PCI group (P=0.018). Thrombectomy strategy was associated with a lower use of stents. Multivariate analysis identified manual thrombectomy (HR=2.08 IC 95% (1.01-4.26); P=0.046), inferior location and short ischemic delay (<180 min) as independent predictors of ST resolution. The cumulative Kaplan-Meier estimate of MACE was not significantly different between the two groups at one, three years follow-up. CONCLUSION: In STEMI patients, manual thrombectomy improves myocardial reperfusion as assessed by the percentage of ST segment resolution and a lower use of stents. However, in this cohort of limited size, this strategy did not translate into an improved cardiovascular outcome at one year follow-up.

Prehospital abciximab in ST-segment elevation myocardial infarction: results of the randomized, double-blind MISTRAL study.

BACKGROUND: The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue. We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) improves ST-segment elevation resolution (STR) after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) is a prospective, randomized, double-blind study. Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). The primary end point was complete (>70%) STR after PCI. Complete STR was not significantly different between the 2 groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow rates before PCI tended to be higher in the ambulance group (46.8% versus 35%, P=0.08) but not after PCI (70.3% versus 65.8%, P=0.49). Slow flow tended to be lower (5.6% versus 13.4%, P=0.07), and distal embolization occurred significantly less often in the ambulance group (8.1% versus 21.1%, P=0.008). One- and 6-month major adverse cardiac event rates were low and similar in both groups. CONCLUSIONS: Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI. However, it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure. Larger studies are needed to confirm these results.

Life-threatening complication during percutaneous ablation of adrenal gland metastasis: Takotsubo syndrome.

A rare life-threatening complication during percutaneous cryoablation of an adrenal gland metastasis from a lung carcinoma is reported. The patient presented hypertensive crisis at the beginning of the thawing cycle, followed by electrocardiographic change which necessitated interruption of the procedure and his transfer to the intensive care unit with suspicion of heart infarct. There was a slight increase in cardiac enzyme levels, and ventricular angiography demonstrated transient hypokinesis-dyskinesis of the mid left ventricular segments without apical involvement, while the coronary arteries showed no significant stenosis on coronarography. These findings led to the diagnosis of Takotsubo cardiomyopathy left ventricular dysfunction syndrome. This is the first case of Takotsubo cardiomyopathy occurring as a complication during percutaneous ablation of an adrenal gland tumor.