Clinical impact and evolution of mitral regurgitation after TAVI using the new generation self-expandable valves.

BACKGROUND: Concomitant mitral regurgitation (MR) impaired prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). It has been suggested that the use of first generation self-expandable valve in patients with significant MR is associated with worse outcome as compared with balloon expandable valve. However, the impact of newer generation transcatheter devices on MR has not been investigated so far. We aim to assess the prognostic impact of MR in patients undergoing TAVI with the first-generation vs. the latest generation of self-expandable valves. METHODS: We analyzed 2964 consecutive patients who underwent TAVI. Patients were classified into 4 groups according to the degree of baseline MR and the generation of self expandable valve implanted. RESULTS: Of 1234 patients with moderate or severe MR, 817 were treated with first generation and 417 patients with second generation valves. Whereas, of 1730 patients with no or mild MR, 1130 were treated with first generation and 600 patients with second generation valves. Although, concomitant moderate-severe MR was found to be an independent predictor of mortality after TAVI, the use of newer generation self expandable valves was associated with higher survival rate at 1 year irrespective of the degree of preprocedural MR. At multivariable analysis the use of newer generation valve was associated with MR improvement throughout 1 year follow-up. CONCLUSION: Baseline moderate-severe MR is associated with an increase in mortality after TAVI. However, the degree of preprocedural MR doesn't impact survival when a second generation self expandable valve is used.

Acoustic radiation of subsonic jets in the vicinity of an inclined flat plate.

Acoustic measurements of turbulent jets in the vicinity of a flat plate, mimicking a neighbouring wing, were compared to results from two wavepacket-based source models previously studied in the literature: the Tailored Green's Function method, which considers the radiation of the turbulent structure in the vicinity of a semi-infinite flat plate, and the Boundary Element Method, which can represent the full geometry of the plate used in the experiments. Particular interest is given to analysing how the angle of attack of the plate (α) affects the sound radiated by an installed jet with trailing edge 6 diameters away from the nozzle and 1 diameter away from the centerline for 0° ≤ α ≤ 45°. The results herein confirm the behaviour identified by the models: the scattered acoustic field follows the rotation of the plate, shifting a silence region with negligible scattered sound, and creating regions with lower noise levels in positions that correspond to the ground for an aircraft with engines under its wings. This is further explored by means of a Mach number analysis for M = 0.5, 0.7, and 0.9, showing that this trend is present whenever trailing-edge scattering of jet disturbances is dominant in the acoustic field.

Prediction of patient-specific post-operative outcomes of TAVI procedure: The impact of the positioning strategy on valve performance.

Prosthesis positioning in transcatheter aortic valve implantation procedures represents a crucial aspect for procedure success as demonstrated by many recent studies on this topic. Possible complications, device performance, and, consequently, also long-term durability are highly affected by the adopted prosthesis placement strategy. In the present work, we develop a computational finite element model able to predict device-specific and patient-specific replacement procedure outcomes, which may help medical operators to plan and choose the optimal implantation strategy. We focus in particular on the effects of prosthesis implantation depth and release angle. We start from a real clinical case undergoing Corevalve self-expanding device implantation. Our study confirms the crucial role of positioning in determining valve anchoring, replacement failure due to intra or para-valvular regurgitation, and post-operative device deformation.

Evaluation of oxidative stress in overweight subjects with or without metabolic syndrome.

Although oxidative stress is considered the underlying mechanism by which dysfunctional metabolism occurs in obese subjects, there are few studies on oxidative stress in overweight subjects. The objective of this study was to verify the influence of metabolic syndrome (MetS) on oxidative stress and antioxidant defense in overweight subjects. There were 123 subjects (50 in the control group and 73 in the overweight group) chosen to participate in this cross-sectional study. The control group included 50 healthy individuals with a BMI between 20 and 24.9 kg/m(2) and without MetS. The overweight group included 73 subjects with a BMI between 25 and 29.9 kg/m(2). Overweight subjects were divided into two groups: with MetS (29 subjects) and without MetS (44 subjects). Control group and overweight group subjects without MetS showed no differences in oxidative stress parameters and total antioxidant capacity (TRAP). Overweight subjects with MetS had higher hydroperoxide concentrations measured by chemiluminescence compared to the control group (P < 0.05), higher hydroperoxide and hydrogen peroxide concentrations determined by ferrous oxidation-xylenol orange assay compared to overweight subjects without MetS (P < 0.001), and higher advanced oxidation protein product (AOPP) concentrations (P < 0.001) compared to the other groups. AOPP was directly correlated with uric acid concentrations. Overweight subjects with MetS had lower TRAP concentrations compared to the control group (P < 0.001). In conclusion, this study showed that overweight subjects with MetS, in contrast to overweight subjects without MetS, have a redox imbalance characterized by increased plasma oxidation and reduced antioxidant capacity.

Early glycoprotein IIb-IIIa inhibitors in primary angioplasty-abciximab long-term results (EGYPT-ALT) cooperation: individual patient's data meta-analysis.

BACKGROUND: Even although time to treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits are still unclear from early pharmacological reperfusion by glycoprotein (Gp) IIb-IIIa inhibitors. Therefore, the aim of this meta-analysis was to combine individual data from all randomized trials conducted on upstream as compared with late peri-procedural abciximab administration in primary angioplasty. METHODS: The literature was scanned using formal searches of electronic databases (MEDLINE and EMBASE) from January 1990 to December 2010. All randomized trials on upstream abciximab administration in primary angioplasty were examined. No language restrictions were enforced. RESULTS: We included a total of seven randomized trials enrolling 722 patients, who were randomized to early (n = 357, 49.4%) or late (n = 365, 50.6%) peri-procedural abciximab administration. No difference in baseline characteristics was observed between the two groups. Follow-up data were collected at a median (25th-75th percentiles) of 1095 days (720-1967). Early abciximab was associated with a significant reduction in mortality (primary endpoint) [20% vs. 24.6%; hazard ratio (HR) 95% confidence interval (CI) = 0.65 (0.42-0.98) P = 0.02, P(het) = 0.6]. Furthermore, early abciximab administration was associated with a significant improvement in pre-procedural thrombolysis in myocardial infarction (TIMI) 3 flow (21.6% vs. 10.1%, P < 0.0001), post-procedural TIMI 3 flow (90% vs. 84.8%, P = 0.04), an improvement in myocardial perfusion as evaluated by post-procedural myocardial blush grade (MBG) 3 (52.0% vs. 43.2%, P = 0.03) and ST-segment resolution (58.4% vs. 43.5%, P < 0.0001) and significantly less distal embolization (10.1% vs. 16.2%, P = 0.02). No difference was observed in terms of major bleeding complications between early and late abciximab administration (3.3% vs. 2.3%, P = 0.4). CONCLUSIONS: This meta-analysis shows that early upstream administration of abciximab in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI) is associated with significant benefits in terms of pre-procedural epicardial re-canalization and ST-segment resolution, which translates in to significant mortality benefits at long-term follow-up.

Early vs. delayed invasive strategy in patients with acute coronary syndromes without ST-segment elevation: a meta-analysis of randomized studies.

Although early percutaneous coronary intervention has been demonstrated to reduce the risk of mortality in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), there are emerging conflicting data as to whether the catheterization needs to be done very early or whether it could be delayed while the patient receives medical therapy. The aim of the current study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing early vs. delayed invasive strategies for NSTE-ACS patients. Medline/CENTRAL and the Web were searched for RCTs comparing early vs. delayed invasive strategies for NSTE-ACS patients. The primary endpoint was all cause mortality, whereas myocardial infarction (MI), coronary revascularizations and 30-day major bleeding complications were secondary end points. Fixed or random effects models were used based on statistical heterogeneity. As a sensitivity analysis, Bayesian random effects meta-analysis was performed in addition to the classical random effects meta-analysis. A total of 5 RCTs were finally included, enrolling 4155 patients. As compared with a delayed strategy, an early invasive approach did not significantly reduce the rates of death [odds ratio (OR) 95% confidence interval (95% CI) = 0.81 (95% CI 0.60-1.09), P = 0.17], MI [OR = 1.18 (95% CI 0.68-2.05), P = 0.55] or revascularizations [OR = 0.97 (0.77-1.24), P = 0.82]. There was a not significant trend toward fewer major bleeding complications for the early invasive approach [OR (95% CI) = 0.76 (0.55-1.04), P = 0.08]. The present meta-analysis shows that for NSTE-ACS patients a routine early invasive strategy does not significantly improve survival nor reduce MI and revascularization rates as compared with a delayed approach.

Cardiac evaluation for simultaneous pancreas-kidney transplantation and incidence of cardiac perioperative complications: preliminary study.

Type I diabetes mellitus (IDDM) is associated with an increased cardiovascular risk, and eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) are consequently accurate for preoperative cardiovascular assessment. According to our algorithm, coronary angiography in SPKT candidates is indicated for patients not only experiencing previous cardiac events or symptoms, but also those with long-standing diabetes (more than 25 years) and/or age over 45 years. Furthermore, a basal transthoracic echocardiographic exam (TTE) is performed to assess cardiac volumes, left ventricular mass, systolic function, and kinesis. The aims of this study were to evaluate perioperative cardiac morbidity and mortality in 18 SPKT-eligible patients, divided into two groups on the basis of the presence/absence of angiographically evident coronary artery disease (CAD), as well as to assess the impact of left ventricular hypertrophy (LVH) on cardiac complications. Cardiac intraoperative morbidity and mortality and postoperative mortality and major morbidity were absent; minor cardiac morbidity consisted only of silent ischemic ECG alterations, without significant differences between groups, although the incidence seemed to be higher in the CAD-positive population. LVH detected preoperatively by TTE exam also failed to correlate with the incidence of such complications. Selection of SPKT candidates by coronary angiography may have positive effects on perioperative cardiac morbidity and mortality. A larger sample size is needed to give the study statistical power. Medium- and long-term follow-up studies are warranted to evaluate the effects of preoperative selection on survival rates.

Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty.

AIM: To investigate the effect of abciximab on microvascular integrity and left ventricular (LV) functional recovery in patients with acute myocardial infarction (MI) treated by primary coronary angioplasty (PTCA). METHODS AND RESULTS: Thirty-one patients (27 males; age 39-76 years) with first, acute MI (<6 h after onset) were randomized to receive either abciximab+primary PTCA (n=17) or primary PTCA alone (n=14). Baseline characteristics of the two groups were similar. Myocardial reperfusion was studied shortly after PTCA by corrected TIMI frame count (cTFC) and intracoronary myocardial contrast echocardiography (MCE), after 48 h by intravenous MCE using intermittent, harmonic power Doppler, and after 1 month by intravenous MCE and 99 mTc-tetrofosmin SPECT. The patients treated with abciximab showed a shorter cTFC (23+/-4 vs 30+/-9 frames; P<0.05), a more preserved microvascular integrity shortly after PTCA (77% vs 55%; P<0.01), after 48 h (86% vs 50%; P<0.005) and at 1-month follow-up (86% vs 54% by MCE, P<0.001, and 68% vs 60% by SPECT, P<0.005) than patients treated with PTCA alone. Abciximab patients also showed a better recovery of LV function, as demonstrated by greater reduction in wall motion score index (1.4+/-0.3 vs 1.5+/-0.2; P<0.05) and increase in LV ejection fraction (53+/-7% vs 48+/-5%; P<0.001). CONCLUSIONS: Abciximab improves microvascular perfusion and LV functional recovery in primary PTCA.

Eptifibatide and abciximab exhibit equivalent antiplatelet efficacy in an experimental model of stenting in both healthy volunteers and patients with coronary artery disease.

Platelet deposition and aggregation are the major determinants of acute thrombosis in coronary stents. We aimed to compare the antiplatelet efficacy of different treatments--glycoprotein (Gp) IIb/IIIa inhibitors and conventional antiaggregants--in an experimental model for stenting. Blood samples were obtained from patients with coronary artery disease (n = 15) and healthy volunteers (n = 8) and incubated either with eptifibatide (2.0 microg/ml), abciximab (3.0 microg/ml), indomethacin (15 microg/ml), or saline. Platelet adenosine diphosphate-induced aggregation in whole blood was assessed for all groups. Blood was also tested in an experimental circulation model containing metallic probes, on which platelet deposition in shear flow conditions was assessed by means of fluorescent-labeled platelet-specific (anti-GpIIIa and Ib) antibodies. Eptifibatide and abciximab, in comparison with indomethacin and no treatment, significantly reduced platelet aggregation (0, 0, 4, and 3 arbitrary units [AU], respectively; p < 0.001), anti-GpIIIa (2.25, 1.83, 11.24, and 13.42 counts per second [cps]/mg, respectively; p < 0.001), and anti-GpIb binding (0.61, 0.61, 1.00, and 1.83 cps/mg, respectively; p < 0.001). Anti-GpIIIa and anti-GpIb binding were significantly correlated (R = 0.36; p < 0.01). Patients showed a higher anti-GpIIIa, but not anti-GpIb binding, than controls (8.43 versus 3.33 cps/mg; p < 0.01), irrespective of treatment. In conclusion, eptifibatide and abciximab show equivalent in vitro antiplatelet efficacy, superior to that of indomethacin. Given the occurrence of GpIIb/IIIa platelet overexpression in the course of coronary artery disease, an extended use of GpIIb/IIIa inhibitors may be proposed to prevent acute thrombosis during routine coronary stenting.

Assessment of coronary vasomotor function: old and new tools.

Atherosclerosis has an impact on the vasomotor reaction of coronary segments to iodinated non-ionic contrast agents. Angiographically normal coronary segments show divergent vasomotor reactions to iodixanol or iopromide according to the presence of, and distance from, a coronary atherosclerotic lesion. The mechanism responsible for the above-mentioned vasomotor effect does not seem to involve flow-mediated vasodilation or endothelial nitric oxide synthesis. On the other hand, a cyclooxygenase product may be, at least in part, responsible for the vasodilating effect of non-ionic agents on epicardial coronary arteries. These findings have potential clinical implications that are herein discussed.

Usefulness of carotid intima-media thickness measurement and peripheral B-mode ultrasound scan in the clinical screening of patients with coronary artery disease.

Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD). In this study the authors evaluated the accuracy of the common carotid IMT measurement in predicting the presence and severity of CAD and the additional information offered by the detection of carotid, iliac, and lower limb plaques. One hundred and fifty consecutive patients were subjected to coronary angiography and carotid, iliac, and lower limb ultrasound scan. The mean value of six IMT measurements of the far wall of the common carotid artery was calculated in each patient. The mean IMT was significantly correlated to the number of stenosed coronary vessels (r = 0.43, p<0.001), although the positive and negative predictive value of mean IMT in identifying patients with CAD was low (81% and 46%, respectively). The combined information offered by IMT measurements and peripheral (carotid, iliac, and lower limb) plaque detection was then used to obtain the best multivariate regression model able to predict CAD status. The multivariate model showed a highly significant multiple correlation coefficient (r = 0.60, p<0.0001) and a sharp improvement in the negative predictive value (92%) with respect to the univariable model. B-mode ultrasound scan including common carotid IMT measurement and peripheral plaque detection may be of clinical value in the screening of patients with CAD.

The impact of coronary artery disease on the coronary vasomotor response to nonionic contrast media.

BACKGROUND: Coronary artery disease (CAD) alters the vasomotor response to a variety of pharmacological agents. We tested the hypothesis that CAD also has an impact on the coronary vasomotor response to radiologic contrast media. METHODS AND RESULTS: We performed quantitative coronary angiography in 42 patients without angiographic evidence of CAD and 38 patients with CAD in the left coronary artery. Angiographically smooth coronary segments (n=235) were analyzed for changes on luminal diameters and coronary venous oxygen saturation in response to 3 media: the nonionic dimer iodixanol, the nonionic monomer iopromide, and the ionic agent ioxaglate. In subjects without CAD, we assessed the effects of intracoronary administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine and of the cyclooxygenase inhibitor indomethacin on such changes. Iodixanol induced coronary vasodilation in subjects without CAD (8.8+/-8.6%, P<0.001). Patients with CAD exhibited no significant diameter changes in segments >/=20 mm apart from a stenosis (4.7+/-9.4%, P=NS) and significant constriction in segments <20 mm from a stenosis (-3.8+/-4.6%, P<0. 05). Similar results were obtained with iopromide, but no changes were found with ioxaglate. All contrast media induced transient (<35 seconds) increases in coronary venous oxygen saturation in all subjects. Indomethacin, but not N(G)-monomethyl-L-arginine, blunted the vasodilating effect of iodixanol and iopromide (by 80% and 76%, respectively; P<0.001). CONCLUSIONS: Nonionic contrast media induce a vasodilatory response in normal vessels not by a mechanism involving increased flow or endothelial nitric oxide synthesis, but rather by depending on preserved vascular cyclooxygenase activity. CAD changes normal epicardial vasodilatory response into vasoconstriction.

Endothelin-1 release from atherosclerotic plaque after percutaneous transluminal coronary angioplasty in stable angina pectoris and single-vessel coronary artery disease.

To assess the effects of percutaneous transluminal coronary angioplasty on endothelin-1 (ET-1) release, we assessed ET-1 concentrations at different sites of the coronary circulation in patients submitted to elective procedures. ET-1 levels immediately downstream from the plaque and ET-1 aortocoronary gradient increased significantly after the procedure, which was related to mechanical wall stress in patients only receiving balloons, but not in those undergoing stent percutaneous transluminal coronary angioplasty. No changes were found in the coronary sinus; these results suggest ET-1 release from the plaque rather than an ischemia/reperfusion-related production from the distal myocardium.

Coronary collateral circulation behaviour and myocardial viability in chronic total occlusion treated with coronary angioplasty.

AIMS: We explored the role of microcirculation integrity following the chronic occlusion of an infarct-related artery to assess the behaviour of collateral circulation during and after reperfusion by coronary angioplasty METHODS AND RESULTS: Eighteen patients with a proximally occluded left anterior descending artery and firm evidence of intercoronary collateral circulation were studied with selective coronary angiography and selective intracoronary myocardial contrast echocardiography, before coronary angioplasty, and at 5 and 15 min and 12 h later. Myocardial enhancement during myocardial contrast echocardiography was evaluated with a semiquantitative score (0-3), which was correlated to basal and 6 months' regional left ventricular wall motion results. 16/18 procedures were successfully performed; four patients with an inadequate acoustic window were excluded. Restenosis was evident at the 6 months' follow-up in two patients. Basal myocardial contrast echocardiography indicated that 81/192 segments from the left anterior descending coronary artery and 90/192 from the right coronary artery were perfused; no perfusion was observed in 21 segments either before or after coronary angioplasty. After coronary angioplasty, the angiographic intercoronary collateral circulation immediately disappeared, and myocardial contrast echocardiography revealed that there was a progressive reduction of segments perfused by the right coronary artery and an increase in segments perfused by the left anterior descending coronary artery. Regional left ventricular wall motion analysis demonstrated that there was abnormal motion in 51/192 segments. There was no improvement in segments with score 0 and abnormal motion after 6 months (100% sensitivity), but 16/17 segments with score 3 did show an improvement (98% specificity). The predictive value of intermediate scores (1-2) in detecting long-term improvement, was only 43%. CONCLUSION: These data show that the adaptive mechanism observed in the behaviour of epicardial and microvascular circulation after reperfusion of a chronic occluded infarct-related artery can vary. In addition, this study clearly shows that microvascular integrity detected by myocardial contrast echocardiography can provide myocardial viability.

Tissue distribution and deposition pattern of a cellulosic parenchyma-specific protein from cassava roots

A protein with a molecular mass of 22 kDa was purified from the cellulosic parenchyma of cassava roots. The amino acid composition of the protein was determined and antibodies generated against the purified protein were used to show that the concentration of the protein remains unchanged during root "tuber" formation. By using a tissue printing technique, as well as weatern blot, it was shown that the cellulosic parenchyma was the only root tissue in which the protein was deposited

[Incidence of peripheral vascular complications in subjects undergoing coronary angioplasty]. / Incidenza di complicanze vascolari periferiche in soggetti sottoposti ad angioplastica coronarica.

The peripheral vascular complications following cardiac catheterization for interventional procedures are increasing. The aim of our study is to evaluate the importance of the early removal of the arterial sheath in reducing vascular complications. We examined 451 consecutive patients, submitted to percutaneous transluminal coronary angioplasty (PTCA) by femoral approach. In 229 patients (Group A), we removed the arterial sheath 12-14 hours after PTCA; in 222 patients (Group B) the arterial sheath was removed as soon as possible at the end of PTCA. In 31 Group A and 5 Group B patients we performed a coronarographic study after 12-14 hours. In total, 16 patients (11 Group A, 5 Group B) presented vascular complications. None of the risk factors that we have considered was predictive for complications, except that iliacofemoral atherosclerotic disease. In patients undergoing complex procedures we have found a greater amount of vascular complications. The coronarographic control revealed some pathologic lesion (dissection, occlusive thrombus) only in patients with clear ischemic signs or symptoms, both in Group A and B. In our opinion, an early removal of the arterial sheath reduces the incidence of vascular complications and the period of in-hospital stay.

Entrapment of a coronary stent in the left main trunk: an easy method for surgical removal.

The use of an intracoronary stent is usually indicated after the acute closure of a coronary vessel following percutaneous transluminal coronary angioplasty. Plaque disruption and dissection, with subsequent spasm and thrombosis, can be contained by this device. In the reported case, acute closure of the left anterior descending coronary artery and of a diagonal branch were caused by the entrapment of a stent proximal to the coronary lesion that it was supposed to treat. An emergency coronary artery bypass graft procedure was required together with removal of the device because of the impending closure of the left main trunk (the site of the stent entrapment). This was successfully performed by means of an easy method, which did not require direct incision of the left main trunk. The less invasive procedure described simplified the operation and probably played an important role in its favorable outcome.