Biomedical subjects
Publications and source records attributed to C Macaya.
The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 226-228, . The duplicate article has therefore been withdrawn.
The aim was to determine in circulating mononuclear cells from patients with erectile dysfunction (ED), the level of expression of endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC) beta1-subunit and phosphodiesterase type-V (PDE-V). Peripheral mononuclear cells from nine patients with ED of vascular origin and nine patients with ED of neurological origin were obtained. Fourteen age-matched volunteers with normal erectile function were used as control. Reduction in eNOS protein was observed in the mononuclear cells from patients with ED of vascular origin but not in those from neurological origin. Although sGC beta1-subunit expression was increased in mononuclear cells from patients with ED, the sGC activity was reduced. However, only the patients with ED of vascular origin showed an increased expression of PDE-V. This work shows for the first time that, independently of the aetiology of ED, the expression of sGC beta1-subunit was increased in circulating mononuclear cells; however, the expression of both eNOS and PDE-V was only modified in the circulating mononuclear cells from patients with ED of vascular origin.
Lead exposure induces dysfunction of the cyclic guanosine monophosphate-dependent vasodilator system through downregulation of soluble guanylate cyclase (sGC) expression. The endothelium not only releases vasodilators but also vasoconstrictors such as endothelin-1 (ET-1). Our aim was to explore the role of the vascular endothelium and ET-1 as possible mediators of lead-induced downregulation of sGC. Isolated aortic segments from Wistar Kyoto rats were incubated in the presence or absence of lead (1 parts per million) for 24 h. Endothelium was mechanically removed in some of the aorta segments. As reported previously, lead exposure induced downregulation of sGC protein expression in the intact aortic segments. However, lead exposure failed to significantly modify sGC-beta1 subunit expression in the endothelium-denuded aortic segments. Incubation with a selective ETA-type receptor inhibitor, BQ-123 (10(-6) mol/l), restored sGC protein expression in lead-exposed intact aortic segments. As it has also been previously observed, incubation in lead-containing medium resulted in the upregulation of cyclooxygenase-2 (COX-2) in the intact aortic segments. Denudation of endothelium partially abrogated this effect of lead. Incubation with BQ-123 prevented the lead-induced upregulation COX-2 in the intact aortic segments. However, neither ET-1 content nor ETA-type receptor expression were modified by lead exposure of the aortic segments. As conclusion, the endothelium through the activation of ETA-type receptors mediates the downregulation of sGC expression by lead in the vascular wall.
This report describes occupational radiation doses of interventional cardiologists over 15 years and assesses action undertaken to optimize radiation protection. Personal dosimetry records of nine staff cardiologists and eight interventional cardiology fellows were recorded using personal dosemeters worn over and under their lead aprons. The hospital in which this study was conducted currently performs 5000 cardiology procedures per year. The hospital has improved its facilities since 1989, when it had two old-fashioned theatres, to include four rooms with more advanced and safer equipment. Intensive radiation protection training was also implemented since 1989. Initially, some individual dose values in the range of 100-300 mSv month(-1), which risked exceeding some regulatory dose limits, were measured over the lead apron. Several doses in the range of 5-11 mSv month(-1) were recorded under the apron (mean = 10.2 mSv year(-1)). During the last 5 years of the study, after the implementation of the radiation protection actions and a programme of patient-dose optimization, the mean dose under the apron was reduced to 1.2 mSv year(-1). Current mean occupational doses recorded under the lead apron are 14% of those recorded during 1989-1992 and those recorded over the apron are 14-fold less than those recorded during 1989-1992. The regulatory dose limits and the threshold for lens injuries might have been exceeded if radiation protection facilities had not been used systematically. The most effective actions involved in reducing the radiation risk were training in radiation protection, a programme of patient-dose reduction and the systematic use of radiation protection facilities, specifically ceiling-suspended protective screens.
OBJECTIVE: To evaluate the potential role of intravascular ultrasound (IVUS) in evaluating patients experiencing an episode of acute stent thrombosis. DESIGN AND SETTING: Prospective observational study in a cardiac catheterisation laboratory in a university teaching hospital. PATIENTS AND INTERVENTIONS: IVUS was used to examine 12 patients undergoing coronary interventions for stent thrombosis to gain further mechanistic insights and to guide treatment. IVUS studies were obtained before and after intervention with a motorised pullback device. MAIN OUTCOME MEASURES: Qualitative and volumetric IVUS analyses. RESULTS: Angiographically, 10 patients had occluded vessels and two patients had intraluminal filling defects within the stent. IVUS showed an occlusive thrombus in all patients. Thrombus volume was 90 (77) mm3, which was 51 (21)% of total stent volume. There was evidence of severe stent underexpansion in most patients and no patient fulfilled standard criteria for optimal stent implantation. Stent malapposition was detected in four patients, edge dissections were seen in two patients, and significant inflow-outflow disease was present in 11 patients. During interventions IVUS findings led to the use of higher pressures or larger balloons than those used during initial stenting in 10 patients. In addition, four patients required additional stenting, whereas a thrombectomy device alone was selected for one patient. After the procedure final minimum stent area (7.1 (2.1) v 5.3 (2) mm2, p < 0.005) and stent expansion (83.2 (17) v 62.1 (15)%, p < 0.005) improved compared with pre-interventional values. However, residual lining thrombus was still visualised in eight patients (25 (19) mm3, accounting for a 17% of final stent volume). CONCLUSIONS: IVUS provides an attractive technique to characterise fully the pattern of stent thrombosis, to identify readily the underlying mechanical predisposing factors, and to guide repeated coronary interventions.
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BACKGROUND: Doppler Tissue Imaging (DTI) has been evaluated in ischaemic heart disease and some cardiomyopathies. In patients with aortic stenosis (AS), left ventricular contraction is slowered. This study aimed to evaluate the possible role of the measurement of isovolumic contraction time (ICT) by DTI in the evaluation of AS severity. METHODS: The study population constitutes 30 patients: 15 with AS (nine severe and six non-severe) and 15 control subjects. All of them had normal systolic function, sinus rhythm, and absence of ischaemic heart disease of conduction abnormalities. ICT was defined as the time from the onset of the QRS complex to the beginning of the DTI systolic wave. The correlation between ICT and aortic area obtained by continuity equation, as well as the diagnostic value of ICT in the identification of severe AS were studied. RESULTS: ICT was significantly increased in patients with severe AS (98+/-27 versus 65+/-21 ms, p=0.024). There was a significant correlation between ICT and aortic area (r=-0.56; p=0.035). The receiver operator characteristic curve of ICT in the identification of severe AS yielded an area under the curve of 0.852 (95% confidence interval: 0.665-1.0). The two best cut-points were >73 ms (88% sensitivity, 77% specificity) and >85 ms (78% sensitivity, 83% specificity). A value of >41 ms had a 100% sensitivity, but only a 17% specificity, and >91 ms showed a 100% specificity, but only a 44% sensitivity. CONCLUSIONS: ICT measured by pulsed-wave DTI is increased in patients with aortic stenosis.
BACKGROUND: Endothelins are important vasoconstrictors and cellular-growth promoters. ETA-specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty. MATERIALS AND METHODS: Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg-1) (group I, n = 10) or no treatment (group II, n = 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization. RESULTS: Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0.57, P = 0.01). This correlation had a lower slope in group I compared with group II (P < 0.001), indicating a smaller amount of neointimal development for a similar degree of injury in bosentan-treated animals. Multivariate regression showed that neointimal response was reduced by oral treatment with bosentan (beta: -0.59 mm2, 95% CI: -1.11/-0.06 mm2). In addition, immunostaining revealed fewer positive endothelin areas in group I arteries. CONCLUSIONS: Oral treatment with bosentan reduces neointimal development following coronary angioplasty in this experimental model.
Plasma lipid metabolic and transfer processes have recently been suggested to play an important role in the development of early restenosis, a major complication of percutaneous transluminal coronary angioplasty (PTCA); in particular, the common variants of genes for cholesteryl ester transfer protein (CETP) and paraoxonase (PONA) have been implicated. We had the opportunity to investigate this question in a large, prospective cohort characterized by quantitative coronary angiography in all subjects. The CETP-TaqIB (intron 1), CETP-MspI (intron 8), and PONA-AlwI (exon 2) polymorphisms were characterized in a cohort of 779 patients of whom 342 ("cases") had developed restenosis (as defined by > 50% loss of lumen compared with immediate postprocedure results) at repeat angiography at 6 months post PTCA. Selected frequencies for CETP B1 and B2 alleles (absence/presence of TaqIB site) were 0.65 and 0.35 (cases) and 0.65 and 0.35 (controls), respectively; frequencies for CETP M1 and M2 alleles (absence/presence of MspI site) were 0.20 and 0.80 (cases), 0.21 and 0.79 (controls), respectively; frequencies for PONA A and B alleles (absence/presence of AlwI site) were 0.73 and 0.27 (cases), 0.72 and 0.28 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for gene-gene interaction, or an association between genotype and restenosis or degree of lumen loss (adjusted for covariates). Our data, collected in the largest study of its kind so far, indicate that the common variants for CETP and PONA are not associated with incidence of restenosis after PTCA, and are therefore not useful markers for risk assessment.
BACKGROUND: It is debatable whether surgical repair is routinely indicated in asymptomatic patients with left ventricular pseudoaneurysms. OBJECTIVE: To evaluate the long term outcome of patients with pseudoaneurysm after myocardial infarction, focusing on those treated conservatively. METHODS: 10 patients with postinfarction left ventricular pseudoaneurysm were followed up over a mean (SD) period of 3.8 (5.2) years. RESULTS: In those treated conservatively (n = 9), cumulative survival was 88.9 (10.5)% and 74.1 (16.1)% at one and four years, respectively. The probability of being free of cardiac death was 88.9 (10.5)% at both one and four years. No patient had complete fatal heart rupture during follow up. Three patients suffered ischaemic stroke (at 1, 11, and 62 months). The cumulative incidence of ischaemic stroke was 10% at one year and 32.5% at four years. CONCLUSIONS: Long term outcome of patients with postinfarction left ventricular pseudoaneurysm is relatively benign, with a very low risk (none in this series) of fatal rupture. Taking into consideration the relatively high risk of stroke, chronic anticoagulant treatment could be considered.
The complexity of recognizing the potential contribution of a number of possible predictors of complex disorders is increasingly challenging with the application of large-scale single nucleotide polymorphism (SNP) typing. In the search for putative genetic factors predisposing to coronary artery restenosis following balloon angioplasty, we determined genotypes for 94 SNPs representing 62 candidate genes, in a prospectively assembled cohort of 342 cases and 437 controls. Using a customized coupled-logistic regression procedure accounting for both additive and interactive effects, we identified seven SNPs in seven genes that, together, showed a statistically significant association with restenosis incidence (P <0.0001), accounting for 11.6% of overall variance observed. Among them are candidate genes for cardiovascular pathophysiology (apolipoprotein-species and NOS), inflammatory response (TNF receptor and CD14), and cell-cycle control (p53 and p53-associated protein). Our results emphasize the need to account for complex multi-gene influences and interactions when assessing the molecular pathology of multifactorial medical entities.
BACKGROUND: The circadian cycle of the endogenous anti-inflammatory system (EAIS) is characterized by a morning increase in cortisol production. Circulating interleukin-6 (IL-6) activates the EAIS. A circadian variation in the onset of myocardial infarction, sudden death, stable angina (SA) and unstable angina (UA) has been reported. The aim of this study was to determine morning cortisol production in coronary heart disease (CHD) patients. MATERIALS AND METHODS: Serum cortisol and IL-6 were measured in 129 patients with either SA (n = 65) or UA (n = 64) and 40 healthy volunteers. Blood samples were taken between 9 : 00 h and 12 : 00 h. The upper normal range of cortisol (25 microg dL-1) was used as a reference to classify patients. RESULTS: Forty-eight patients had elevated cortisol levels (ECL) (32.5 +/- 5.4 microg dL-1), while 81 patients had normal cortisol levels (NCL) (15.7 +/- 5.9 microg dL-1). In NCL patients, IL-6 levels (26.6 pg mL-1, ranged from 0.2 to 183.7) were significantly higher (P < 0.004) than in ECL patients (9.70 pg mL-1, range 0.07-56.5). Forty-eight patients with UA belonged to the NCL group of patients, while only 16 UA patients belonged to the ECL group (chi(2) = 0.000). Thirty-two patients with SA belonged to the ECL group, and 33 to the NCL group (chi(2) = 0.08). CONCLUSIONS: Patients with 'inappropriately' normal morning cortisol production had high IL-6 levels. 'Inappropriately' normal cortisol, detected in 75% of UA and 50% of SA patients, may be insufficient for limiting inflammation. These findings have novel clinical implications and suggest new therapeutic approaches in the treatment of these patients.
BACKGROUND: Although it has been suggested that elevation of CK-MB after percutaneous coronary intervention is associated with adverse clinical outcomes, limited data are available in the setting of coronary bypass grafting. The aim of the present study was to determine the incidence, predictors, and prognostic significance of CK-MB elevation following multivessel coronary bypass grafting (CABG). METHODS AND RESULTS: The population comprises 496 patients with multivessel coronary disease assigned to CABG in the Arterial Revascularization Therapies Study (ARTS). CK-MB was prospectively measured at 6, 12, and 18 hours after the procedure. Thirty-day and 1-year clinical follow-up were performed. Abnormal CK-MB elevation occurred in 61.9% of the patients. Patients with increased cardiac-enzyme levels after CABG were at increased risk of both death and repeat myocardial infarction within the first 30 days (P=0.001). CK-MB elevation was also independently related to late adverse outcome (P=0.009, OR=0.64). CONCLUSIONS: Increased concentrations of CK-MB, which are often dismissed as inconsequential in the setting of multivessel CABG, appear to occur very frequently and are associated with a significant increase in both repeat myocardial infarction and death beyond the immediate perioperative period.
BACKGROUND: Percutaneous coronary revascularization (PCI) has been increasingly applied to unprotected left main trunk (LMT) lesions, with varied long-term success. This study attempts to define the predictors of outcome in this population. METHODS AND RESULTS: Two hundred seventy-nine consecutive patients who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six percent of these patients were deemed inoperable or at high surgical risk. Thirty-eight patients (13.7%) died in hospital, and the rest were followed up for a mean of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent correlates of all-cause mortality were left ventricular ejection fraction </=30%, mitral regurgitation grade 3 or 4, presentation with myocardial infarction and shock, creatinine >/=2.0 mg/dL, and severe lesion calcification. For the 32% of patients <65 years old with left ventricular ejection fraction >30% and without shock, the prevalence of these adverse risk factors was low. No periprocedural deaths were observed in this low-risk subset, and the 1-year mortality was only 3.4%. CONCLUSIONS: Patients undergoing unprotected LMT PCI have frequent serious comorbidities and consequently have high event rates. PCI may be an alternative to CABG for a select proportion of elective patients and may also be appropriate for highly symptomatic inoperable patients. Meticulous follow-up of hospital survivors is required because of the rather high mortality during the first few months after treatment.
BACKGROUND: Observational studies in selected patients have shown remarkably low restenosis rates after ultrasound-guided stent implantation. However, it is unknown whether this implantation strategy improves long-term angiographic and clinical outcome in routine clinical practice. Methods and Results-- A total of 550 patients with a symptomatic coronary lesion or silent ischemia were randomly assigned to either ultrasound-guided or angiography-guided implantation of </=2 tubular stents. The primary end points were angiographic dichotomous restenosis rate, minimal lumen diameter, and percent diameter stenosis after 6 months as determined by quantitative coronary angiography. Secondary end points were the occurrence rates of major adverse cardiac events (death, myocardial infarction, coronary bypass surgery, and repeat percutaneous intervention) after 6 and 12 months of follow-up. At 6 months, repeat angiography revealed no significant differences between the groups with ultrasound- or angiography-guided stent implantation with respect to dichotomous restenosis rate (24.5% versus 22.8%, P=0.68), minimal lumen diameter (1.95+/-0.72 mm versus 1.91+/-0.68 mm, P=0.52), and percent diameter stenosis (34.8+/-20.6% versus 36.8+/-19.6%, P=0.29), respectively. At 12 months, neither major adverse cardiac events (relative risk, 1.07; 95% CI 0.75 to 1.52; P=0.71) nor repeat percutaneous interventions (relative risk 1.04; 95% CI 0.64 to 1.67; P=0.87) were reduced in the ultrasound-guided group. CONCLUSIONS: This study does not support the routine use of ultrasound guidance for coronary stenting. Angiography-guided optimization of tubular stents can be performed with comparable angiographic and clinical long-term results.
The objectives of the Race Car study were to assess the safety and efficacy of the Medtronic AVE S670 stent, a new-generation stent with a modular design consisting of interconnected sinusoidal rings allowing improved flexibility with good conformability and scaffolding. A total of 285 stents were implanted in 267 patients with (un)stable angina pectoris who underwent angioplasty of a single de novo lesion in a native coronary artery with a diameter between 3.0 and 4.0 mm. Available stent lengths were 9, 12, and 15 mm. The primary endpoint was the 6-month restenosis rate. Secondary endpoints were device and procedural success and major adverse cardiac event (MACE)-free survival at 1 and 6 months. All patients received the study stents and no other stents were used (angiographic success: 100%). Eight patients experienced a MACE during hospital admission (Q-wave MI in 2, non-Q-wave MI in 4, TLR in 2). A procedural success was obtained in 97% of the patients. There were no additional events at 1 month. The clinical endpoints encountered at 6 months were Q-wave MI in 1, bypass surgery in 3, and repeat angioplasty in 25 (MACE-free survival: 86.5%). Quantitative angiographic results were the minimum lumen diameter increased from 1.05 +/- 0.32 before to 2.73 +/- 0.39 mm after stent implantation. At follow-up, the loss in diameter was 0.74 +/- 0.50 mm. The loss index was 0.45 +/- 0.31 and restenosis rate was 13.4%. This study has demonstrated that the S670 stent in patients with (un)stable angina pectoris requiring intervention of a single lesion has a low acute and 6-month major event rate and a low angiographic restenosis rate.
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.
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