Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood.

BACKGROUND AND OBJECTIVES: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. METHODS AND RESULTS: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s(-1). The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. CONCLUSIONS: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

A case of platypnea-orthodeoxia syndrome caused by the interaction between the presence of corrected transposition of the great arteries and patent foramen ovale.

A 42-year-old was admitted to our institution for recurrent episodic dyspnea on exertion. The patient had also a history of recurrent transient ischemic attacks. Careful history taking revealed that she developed dyspnea in an upright position, whereas the symptoms were relieved in a supine position (platypnea). The patient was given the diagnosis of platypnea-orthodeoxia syndrome. Transthoracic echocardiography showed cardiac situs solitus levocardia with great artery transposition with intact interventricular septum, patent foramen ovale (PFO) and moderate right atrial dilatation. Agitated saline contrast injection demonstrated the presence of spontaneous right-to-left shunt. The patient underwent transcatheter closure of PFO. After percutaneous closure of PFO patient became asymptomatic and hypoxemia induced by orthostatic conditions did not appear again. A transthoracic echocardiography performed after two months, showed the complete closure of PFO, without residual shunt.

Admission glycemia and markers of inflammation are independent outcome predictors in primary PCI in non-diabetic patients.

AIM: To assess the prognostic value of admission plasma glucose (APG) respect to clinical variables and inflammatory markers in a selected population of non-diabetic patients with ST elevation myocardial infarction (STEMI) treated with primary angioplasty (primary coronary intervention, PCI). METHODS: A total of 188 consecutive non-diabetic STEMI patients undergoing primary PCI were divided into four quartiles based on APG (<117, 117-140, 141-170, >170 mg/dL). Combined end-point of major adverse cardiac events (MACE) was defined as death, acute heart failure, re-infarction, unstable angina or inducible ischemia. RESULTS: Event-free survival from MACE was significantly (P<0.001) correlated with APG quartiles and decrease from the lowest to the highest: 6 months event-free survival was 89.3%, 77.4%, 59.1%, 42.5%. Patients with higher APG were characterized by a significantly higher Killip class (P<0.001), higher serum creatinine (P<0.05) on admission, and a lower rate of thrombolysis in myocardial infarction (TIMI) 3 flow after PCI (P<0.05). Multivariate analysis showed APG>170 mg/dL (hazard ratio [HR] 2.39, 95% confidence interval [CI] 1.24 to 4.65, P<0.01), admission high-sensitivity C-reactive protein level (HR 1.19, 95% CI 1.07 to 1.31, P<0.001), white blood cells count (HR 1.07, 95% CI 1.00 to 1.14, P<0.04) and heart rate (HR 1.02, 95% CI 1.00 to 1.04, P<0.02) to be independent predictors of MACE. CONCLUSION: Admission glycemia and inflammatory markers are independent predictors of MACE in the mid-term follow-up in non-diabetic STEMI treated with primary PCI. Further investigations are needed to study the pathogenesis of stress hyperglycaemia, interactions with mechanisms of inflammation and whether early and aggressive treatment with insulin may influence outcome of primary PCI.

DES implantation in saphenous vein and left internal mammary grafts.

Forty percent of patients treated with CABG need further revascularizations after 10 years mainly due to saphenous--more than arterial--graft disease. In this issue, the Authors make a critical review of current available literature on the treatment of saphenous and arterial graft disease, a subset of lesions for which a clear consensus for DES use is still lacking. The Authors examine both the positive and negative aspects of DES use in this setting. Percutaneous revascularizations with DES are feasible and safe. The antiproliferative properties of DES seem to be effective even in the treatment of bypass disease, in particular in saphenous grafts. The clinical efficacy of a treatment with DES is expressed mainly in the reduction of in-stent restenosis and, therefore, in the rates of target lesion revascularization (TLR). Moreover, the use of DES is not associated to higher rates of stent thrombosis and, in case of reintervention, recurrence rates seem to be limited. However, the benefit provided by DES in prevention of restenosis may be limited by the progression of the disease in other segments than those treated with stents. Percutaneous treatment of arterial bypass with DES is feasible and safe. Most of available data on DES are on anastomotic disease (data on bypass ostium and shaft are too scarce to draw any conclusion). In this case, where the use of stents is imperative, there is no evidence of advantages gained by the use of DES over BMS in terms of new revascularizations. Some unanswered questions on DES use in this setting still remain. For this reason new randomized trials are required to definitively give a reliable answer on DES efficacy in this subset of lesions.

Endovascular intervention in the treatment of congenital heart disease in adults.

Over the last years, endovascular intervention have become an important part of treatment in patients with congenital heart disease particularly for residual defects after surgery done in infancy. These transcatheter procedures can be described as dilatation of stenotic sites (angioplasty, endovascular stenting and valvuloplasty) or as a closure of anomalous openings (device closure defects and vascular embolisation). Balloon valvuloplasty, without or with stent, is the procedure of choice in adults with pulmonary valve stenosis, pulmonary arteries stenosis, bicuspid aortic valve stenosis without calcification, aortic re-coarctation. Treatment of native aortic coarctation is still under debate. Devices for closing atrial and ventricular septal defects or patent ductus arteriosus have been developed and are now widely used. Transcatheter, plug or coil occlusion is nowadays the goal treatment in a wide range of arterial and venous vascular connections. This review describes the current role of each major catheter-directed therapy in the treatment of congenital heart disease in adults.

Drug-eluting stents: towards new endpoints.

Drug-eluting stents (DES) have significantly reduced the rates of in-stent restenosis (ISR). As previously observed with bare-metal stents (BMS), either patient's clinical characteristics and lesion morphology may influence the risk of recurrence even with DES. In this review we will focus on the most recent available data on clinical settings where DES efficacy on long-term outcomes are largely unknown. In particular, we report on very complex lesions (bifurcations, small vessels, chronic total occlusions, in-stent restenosis) myocardial infarction, multivessel disease, treatment of bypass graft and of unprotected left main disease. Several issues are still open on DES routinary use for these indications, mainly as far as stent thrombosis is concerned. Recent pathological studies show that DES are characterized by chronic inflammatory infiltrates and delayed endothelialization. Therefore, this effect could translate in a ''vulnerable period'' for thromboses longer than with BMS. Even though large meta-analysis have excluded higher rates of stent thrombosis with DES rather than with BMS, few cases of unusual very late stent thrombosis have been described, pointing out that this problem seems to be still unsolved. Although DES provide better angiographic outcomes in each clinical setting, further randomized studies are running to assess their safety and efficacy on currently off-label indications.

Clinical utility of IVUS in 2005.

Intravascular ultrasounds (IVUS) allowed an innovative visualization of coronary artery disease. This technique developed first in the research field and, then, it was introduced in clinical practice as a supplement to coronary angiography in diagnosis of the severity of ischemic heart disease. The characteristic tomographic view of coronary plaque supplied by IVUS allowed to overcome the limitations of coronary angiography and to add important supplemental information in understanding the mechanism of action of several interventional devices. In this review we analyze current indications of use of IVUS in clinical practice and the future applications of IVUS-related techniques for the diagnosis of coronary artery disease.

Inhibitors of platelets glycoprotein IIb/IIIa (GP IIb/IIIa) receptor: rationale for their use in clinical cardiology.

The glycoprotein IIb/IIIa (GP IIb/IIIa) receptor is the most important receptor involved in platelet aggregation. A stable GP IIb/IIIa inhibition is required when a massive platelet activation triggers thrombosis. Three GP IIb/IIIa inhibitors are currently approved for clinical use: abciximab, tirofiban and integrilin. Their different pharmacodynamic and pharmacokinetic properties reflect a different efficacy in platelet inhibition.

Procedural and long-term results of sirolimus-eluting stent in patients at high risk for restenosis.

AIM: In-stent restenosis still affects 10-50% of long-term outcome after percutaneous coronary intervention (PCI). Large clinical trials have shown that sirolimus-eluting stents (SES) have reduced restenosis rate to 0-9% in lesions at low-moderate risk. The aim of this study was to evaluate long-term clinical and angiographic outcome of SES in a real world population, at very high risk of restenosis. METHODS: Ninety lesions at high risk of restenosis (lesion length >20 mm, target vessel diameter <2.5 mm, in-stent diffuse restenosis, total occlusions and complex lesions on bypass grafts and bifurcations) were treated in 75 patients. A follow-up was scheduled at 6 months. RESULTS: Restenosis rate was 16.6% with a focal pattern of presentation in most cases. Subacute in-stent thrombosis occurred in 2.2%. Resteno-sis occurred mainly in small vessels, diabetic patients and in vessels previously treated with brachytherapy. CONCLUSION: The treatment of lesions at high risk of restenosis with SES is safe with a low restenosis rate at follow-up. An aggressive and prolonged antiplatelet regimen is mandatory because of high subacute in-stent thrombosis rates.

Exercise echocardiography versus exercise electrocardiography in the diagnosis of coronary artery disease in hypertension.

In hypertension, coronary artery disease (CAD) can be overestimated by stress electrocardiography (ECG) and scintigraphy due to frequent false-positive results. Exercise tests are also limited by an excessive blood pressure increase, and pharmacologic pressure normalization decreases the accuracy of the test. The aim of this study was to assess the accuracy of exercise echocardiography as an alternative test for CAD detection in hypertension, both before and after adequate blood pressure control. We studied 59 hypertensive and 59 normotensive patients undergoing coronary angiography for chest pain. Upright bicycle exercise ECG and echocardiographic tests were performed in each group in the absence of therapy; in hypertensives, the tests were repeated a day apart after blood pressure normalization with sublingual nifedipine. Significant CAD (lumen narrowing >50%) was detected in 22 hypertensive and 41 normotensive patients. In the two groups, sensitivity, specificity, and diagnostic accuracy of exercise echocardiography performed before treatment were not statistically different (95%, 94%, 94% in hypertensives and 82%, 77%, 83% in normotensives, respectively), but were significantly higher than for the exercise ECG test (68%, 70%, and 69%, respectively). After blood pressure lowering, exercise echocardiography sensitivity slightly decreased (91%), whereas specificity (100%) and diagnostic accuracy (96%) did not vary; on the contrary, exercise ECG sensitivity decreased to 45%. Therefore, according to our data, exercise echocardiography can be an accurate test and more reliable than exercise ECG to detect CAD in normotensives as well as in hypertensives. Normalization of blood pressure with nifedipine does not affect its accuracy, but markedly reduces the sensitivity of exercise ECG.