Luis Azcona

Long-Term Clinical and Echocardiographic Follow-Up After Percutaneous Mitral Valvuloplasty With the Inoue Balloon

BACKGROUND The objective of this study was to assess the long-term clinical outcome and valvular changes (area and regurgitation) after percutaneous mitral valvuloplasty (PMV). METHODS AND RESULTS After PMV, 561 patients were followed up for 39 (+/-23) months and clinical/echocardiographic data obtained yearly. Kaplan-Meier and Cox regression analyses were performed to estimate event-free survival, its predictors, and the relative risks of several patient subgroups. There were several nonexclusive events: 19 (3.3%) cardiac deaths, 55 (9.8%) mitral replacements, 6 (1%) repeated PMVs, 56 (10%) cases of restenosis, and 108 (19%) cases of clinical impairment. Survival free of major events (cardiac death, mitral surgery, repeat PMV, or functional impairment) was 69% at 7 years, ranging from 88% to 40% in different subgroups of patients. Wilkins score was the best preprocedural predictor of mitral opening, but the procedural result (mitral area and regurgitation) was the only independent predictor of major event-free survival. Mitral area loss, though mild [0.13 (+/-0.21)cm2], increased with time and was >/=0.3 cm2 in 12%, 22%, and 27% of patients at 3, 5, and 7 years, respectively. Regurgitation did not progress in 81% of patients, and when it occurred it was usually by 1 grade. CONCLUSIONS Seven years after PMV, more than two thirds of patients were in good clinical condition and free of any major event. The procedural result was the main determinant of long-term outcome, although a high score had also negative implications. Mitral area decreased progressively over time, whereas regurgitation did not tend to progress.

Different expression of proteins in platelets from aspirin-resistant and aspirin-sensitive patients

The aim of the present study was to analyse differences in the protein expression profile between platelets from aspirin (ASA)-resistant patients and ASA-sensitive patients. We analysed platelets from 51 clinically stable coronary ischaemic patients taking ASA (100 mg/day) divided into ASA-resistant (n=25) and ASA-sensitive (n=26) based on a platelet functionality test (PFA-100). Proteins associated with cytoskeleton, energetic metabolism, oxidative stress, inflammation and cell survival were analysed by two-dimensional electrophoresis and mass spectrometry. The expression of two gelsolin precursor isotypes and one F-acting capping protein isotype was decreased in ASA-resistant platelets (p<0.05). The expression of glyceraldehyde 3-phosphate dehydrogenase was increased in the ASA-resistant platelets (1751.1 + or - 220.6 vs. 4273.3 + or - 971.7, 95% confidence interval [CI] 1815.11 to 4061.2, p=0.001). It was accompanied by a reduced expression and activity of 1,6-bisphosphate aldolase in platelets without changes in the content of pyruvate. A reduced expression of gluthathione-S-transferase and the protein disulfide isomerase isotype 1 was found in ASA-resistant platelets. The protein expression of the chloride intracellular channel isotype 1 was increased in ASA-resistant platelets (21.3 + or - 3.8 vs. 48.8 + or - 6.0, CI 29.5 to 45.95, p=0.03) while the expression of two HSP60 and two HSP71 isotypes was decreased. No changes were observed in proteins associated with inflammation. In conclusion, ASA-resistant and ASA-sensitive platelets are different in terms of the level of expression of proteins associated with mechanisms such as energetic metabolism, cytoskeleton, oxidative stress and cell survival which may be associated with their different ability to respond to ASA.

Proteomic changes related to "bewildered" circulating platelets in the acute coronary syndrome.

Acute coronary syndromes (ACS) are associated with platelet activation. The aim of the present study was to study the protein expression level associated with glycolysis, oxidative stress, cytoskeleton and cell survival in platelets obtained during an ACS. Platelets from 42 coronary ischemic patients, divided into patients admitted within 24 h after the onset of chest pain (ACS group; n=16) and patients with stable coronary ischemic disease (CAD, n=26), were analyzed using proteomics. The expression levels of proteins involved in cellular cytoskeleton (F‐actin capping, β‐tubulin, α‐tubulin isotypes 1 and 2, vinculin, vimentin and two Ras‐related protein Rab‐7b isotypes), glycolysis pathway (glyceraldehyde‐3‐phosphate dehydrogenase, lactate dehydrogenase and two pyruvate kinase isotypes) and cellular‐related antioxidant system (manganese superoxide dismutase) and even the expression and activity of glutathione‐S‐transferase were significantly reduced in platelets from ACS patients compared to CAD patients. Moreover, reduction in the expression of proteins associated with cell survival such as proteasome subunit β type 1 was also observed in ACS platelets compared with CAD platelets. Principal component and logistic regression analysis suggested the existence of factors (proteins) expressed in the platelets inversely associated with acute coronary ischemia. In summary, these results suggest the existence of circulating antioxidant, cytoskeleton and glycolytic‐“bewildered” platelets during the acute phase of a coronary event.

Initial results and long-term clinical and angiographic implications of coronary stenting in elderly patients

Results of 378 consecutive elderly patients (> or = 65 years) undergoing coronary stenting were compared with those of 601 younger patients. Although the restenosis rate was similar in the 2 groups, age > or = 65 years was an independent predictor of in-hospital mortality (relative risk 5.4, 95% confidence interval 1.2 to 20.1) and follow-up mortality (relative risk 2.8, 95% confidence interval 1.3 to 6.1).

Results (> 6 months) of stenting of > 1 major coronary artery in multivessel coronary artery disease

Multivessel percutaneous transluminal coronary angioplasty (PTCA) is associated with a high requirement for further revascularization procedures. Although stenting can reduce restenosis and clinical events after 1-vessel intervention, little information is available after multivessel coronary stenting. We followed up 136 patients (9% of 1,481 undergoing stenting in our center) who had had stent implantation in at least 2 different major native coronary arteries and were followed-up for >6 months. Each patient had received a mean of 2.3 +/- 0.6 stents (1.13 +/- 0.4 stents per lesion) and procedural success was 95%. In-hospital complications included 1 death, 1 Q-wave infarction, 5 non-Q-wave myocardial infarctions, and 1 repeat PTCA. After a mean of 18 +/- 13 months, 7 patients died (3 of heart failure, 4 of noncardiac causes), 2 required coronary bypass surgery, 1 had a myocardial infarction, 13 target vessel repeat PTCA, and 4 non-target vessel PTCA. Survival free of major cardiac events was 75% at 3 years. A history of heart failure, dilation of a restenotic lesion, and 3-vessel dilation were independent negative predictors of event-free survival. Angiographic follow-up was available in 86 patients: 56 (65%) were restenosis free, 23 (27%) had 1-vessel restenosis, and 6 (7%) had 2-vessel and 1 patient 3-vessel restenosis. Restenosis per vessel was 23% (41 of 177). Reference diameter, past-PTCA minimal luminal diameter, and length of the stent were independent predictors of restenosis. We conclude that multivessel stenting provides good midterm results in selected patients with multivessel coronary artery disease. Midterm events are less frequent than previously reported after balloon PTCA.

Contrast agents provide a faster learning curve in dipyridamole stress echocardiography

Aim: Interobserver variability is an important limitation of the stress echocardiography and depends on the echocardiographer training. Our aim was to evaluate if the use of contrast agents during dipyridamole stress echocardiography would improve the agreement between an experienced and a non-experienced observer in stress echo and therefore if contrast would affect the learning period of dypyridamole stress echo. Methods and results: Two independent observers without knowledge of any patient data interpreted all stress studies. One observer was an experienced one and the other had experience in echocardiography but not in stress echo. Two observers analysed 87 non-selected and consecutive studies. Out of the 87 studies, 46 were performed without contrast administration, whereas i.v. contrast (2.5 g Levovist® by two bolus at rest and at peak stress) was administered in 41. In all cases, second harmonic imaging and stress digitalisation pack was used. The agreement between observers showed a κ index of 0.58 and 0.83 without and with contrast administration, respectively. Conclusions: The use of contrast agents provides a better agreement in the evaluation of stress echo between an experienced and a non-experienced observer in stress echo. Adding routinely contrast agents could probably reduce the number of exams required for the necessary learning curve in stress echocardiography.

Impact of Clopidogrel and Aspirin Treatment on the Expression of Proteins in Platelets from Type-2 Diabetic Patients with Stable Coronary Ischemia

The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone.

Old and new molecular mechanisms associated with platelet resistance to antithrombotics.

ABSTRACTCurrent available data show that about 5 to 40% of coronary patients treated with conventional doses of antithrombotic drugs do not display adequate antiplatelet response. Nowadays, aspirin remains the main antiplatelet therapy. However, a significant number of patients show platelet resistance to aspirin therapy, and recurrent thrombotic events occur. Combined antithrombotic therapies with thienopyridines, such as clopidogrel have been used to resolve this problem. However, clopidogrel treatment has been also associated with wide response variability, and non-responsiveness to clopidogrel also occurs in some patients. Therefore, the main question arising about the antithrombotic therapy is why particular patients do not benefit from the therapy and how they might be identified to improve their treatment. Different hypotheses have been suggested, including genetic factors, platelet heterogeneity, non-compliance and others. However, it is probably that many molecular mechanisms involved in platelet resistance to antithrombotic therapies still remains unknown. New technologies, such as proteomics and genetic, are beginning to show new unknown biological biomarkers and molecular mechanisms which may be associated with platelet antithrombotic drug resistance.

Effects of Coronary Prestenting Platelet Inhibition on Coronary Poststenting Inflammation

The aim of this study was to analyze the effect of 2 antiplatelet regimens on the inhibition of GP IIb/IIIa-dependent platelet activation and their association with the poststenting inflammatory response. Seventeen patients with acute myocardial infarction were divided into 2 groups: (A) clopidogrel plus tirofiban infusion administered together during inclusion (n = 10); (B) clopidogrel administered at inclusion and followed 2 hours after by tirofiban (n = 7). Blood samples were obtained at inclusion and at 24 and 48 hours after stenting. Before stenting, a greater reduction of GP IIb/IIIa-dependent platelet activation was found in both groups, although it was greater in group A than in group B. This statistical difference was not observed at 24 and 48 hours after the procedure. At 48 hours after stenting, interleukin-6, interleukin-10, soluble intracellular adhesion molecule-1, and soluble CD40 ligand plasma values were not different between experimental groups. By proteomics, different isoforms of the following proteins were identified: alpha 1-antitrypsin (ATT-1), fibrinogen gamma chain, apolipoprotein A-IV, apolipoprotein A-I, vitamin D binding protein, haptoglobin, and serotransferrin. At 48 hours after stenting, only the plasma expression of the ATT-1 isoform 5 was significantly increased in group A compared with group B. In conclusion, a greater inhibition of GP IIb/IIIa-dependent platelet activation before stenting was not correlated with a different inflammatory activity early after stenting.

Vasculitis leucocitoclástica en relación con ticlopidina

In the last five years the combination of ticlopidine plus aspirin has been the treatment of choice to avoid thrombi formation after the implantation of intracoronary stents. The adverse effects observed include the appearance of a maculopapulous, pruritic, painless, cutaneous rash. We present the case of a patient who developed leucocytoclastic vasculitis associated with the administration of ticlopidine.