Substandard life-saving drugs: a global concern.
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Adverse Drug Reaction Reporting Systems↗
Biomedical subjects
Filippo Crea
Publications and source records attributed to Filippo Crea.
Left main and saphenous vein graft spasm: an unusual association.
We present a case of left main spasm which was associated with spasm of a saphenous vein graft. This case emphasizes the importance of excluding an excessive vasoconstrictory response in patients treated with percutaneous coronary interventions.
Coronary Vasospasm↗
Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function.
AIMS: Recent data suggest that the administration of bone marrow-derived stem cells (BMSC) might improve myocardial perfusion and left ventricular (LV) function after acute myocardial infarction (AMI). The aim of this study was to assess spontaneous mobilization of BMSC expressing the haematopoietic and endothelial progenitor cell-associated antigen CD34+ after AMI and its relation to post-infarction remodelling. METHODS AND RESULTS: Peripheral blood concentration of CD34+ BMSC was measured by flow cytometry in 54 patients with AMI, 26 patients with chronic stable angina (CSA), and 43 normal healthy subjects. In patients with AMI, LV function was measured by 2D-echocardiography. Eighteen AMI patients were reassessed at 1 year. BMSC concentration was higher in patients with AMI (mean peak value: 7.04+/-6.27 cells/microL), than in patients with CSA (3.80+/-2.12 cells/microL, P=0.036) and in healthy controls (1.87+/-1.52 cells/microL, P<0.001). At multivariable analysis statin use (P<0.001), primary percutaneous intervention (P=0.048) and anterior AMI (P=0.05) were the only independent predictors of increased BMSC mobilization after AMI. In the 28 patients without subsequent acute coronary events reassessed at 1 year follow-up, CD34+ cell concentration was an independent predictor of global and regional improvement of LV function (r=0.52, P=0.004 and r=-0.41, P=0.03, respectively). CONCLUSION: AMI is followed by enhanced spontaneous mobilization of BMSC, in particular, in patients on statin therapy and following a primary percutaneous intervention. More importantly persistent spontaneous mobilization of BMSC might contribute to determine a more favourable post-AMI remodelling.
Antigens, CD34↗
Association of endothelin-1 with transient myocardial ischemia in patients with unstable angina pectoris.
In this study we assessed whether serum endothelin-1 levels were associated with indexes of disease severity in unstable angina, including troponin I, C-reactive protein, and transient myocardial ischemia. Endothelin-1 levels were higher in patients who had transient myocardial ischemia and in those who had 3-vessel disease on angiography but were not significantly correlated with levels of C-reactive protein and troponin I.
Aged↗
Hibernating myocardium, apoptosis, and a simple mathematical task.
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Apoptosis↗
Persistent systemic inflammation in unstable angina is largely unrelated to the atherothrombotic burden.
OBJECTIVES: The aim of this study was to assess the relationship between systemic inflammation, atherosclerosis, and thrombosis in two distinct clinical models of atherothrombosis. BACKGROUND: Persistent unstable angina (UA) is commonly associated with coronary thrombosis and persistent systemic inflammation. METHODS: We assessed circulating markers of activation of the thrombotic and fibrinolytic cascades and systemic soluble and cellular markers of inflammation on admission in 40 patients with persisting UA (Braunwald class IIIB; group 1) and 30 patients with Leriche-Fontaine stage IIB-III peripheral artery disease awaiting revascularization (group 2). RESULTS: The extent of atherosclerosis (p < 0.01) and activation of the coagulation system were greater in group 2, which had higher thrombin-antithrombin III complexes and D-dimer levels (2.7 and 24.4 microg/l, respectively), than in group 1 (2.0 microg/l and 12.9 microg/l, p = 0.02 and p = 0.0001, respectively). In contrast, C-reactive protein and interleukin-6 levels were higher in group 1 (7.6 pg/ml and 7.8 pg/ml, respectively) than in group 2 (4.5 pg/ml and 3.0 pg/ml, p < 0.01 and p = 0.03, respectively). Moreover, neutrophil activation was only found in group 1 (neutrophil myeloperoxidase content -4.0 arbitrary units vs. +3.4 arbitrary units in group 2, p < 0.0001). These differences persisted during the initial three days of hospitalization. CONCLUSIONS: Such a large, consistent discrepancy between atherothrombotic burden and systemic inflammation suggests that atherothrombosis, by itself, is an unlikely cause of persisting, recurring UA. An understanding of the primary inflammatory mechanisms of persistent and recurrent coronary instability could open the way to novel therapeutic strategies.
Aged↗
Effect of spinal cord stimulation on spontaneous and stress-induced angina and 'ischemia-like' ST-segment depression in patients with cardiac syndrome X.
AIMS: A significant number of patients with cardiac syndrome X (CSX) present frequent episodes of severe chest pain, refractory to maximal multi-drug therapy. A few, small, uncontrolled data suggested that spinal cord stimulation (SCS) may have favourable clinical benefits in these patients. METHODS AND RESULTS: We studied 10 CSX patients who were being treated by SCS for refractory angina pectoris for 17+/-16 months (median 8). Patients were randomized to either continue or withdraw SCS for a period of 3 weeks and were then crossed over to the other condition for a further 3-week period. During each 3-week period patients kept a detailed diary of angina episodes occurring in the last 2 weeks of each phase. Furthermore, at the end of each 3-week period, angina status was also assessed by Seattle Angina Questionnaire (SAQ), a 0-100 visual analogue scale (VAS), and patients underwent 24-h Holter monitoring (HM) and echocardiographic dobutamine stress test (DST). Compared with the withdrawal phase, SCS reduced the number (P=0.01), duration (P=0.022), and severity (P=0.011) of angina episodes, and nitrate consumption (P=0.042). SAQ scores (P< or =0.013 for all) and VAS (P<0.001) were also improved, the number of episodes of ST-segment depression on HM was decreased (P=0.014), and time to angina (P=0.045) and to 1 mm ST-segment depression (P=0.04) during DST were both prolonged by SCS. CONCLUSIONS: Our data point out that SCS may be an effective form of treatment in patients with CSX suffering from frequent angina episodes significantly impairing quality of life (QOL) and refractory to maximally tolerated drug therapy.
Aged↗
Safety and feasibility of coronary sinus left ventricular leads extraction: a preliminary report.
BACKGROUND: transvenous positioning of the left ventricular (LV) lead in a branch of the coronary sinus (CS) is generally the preferred implantation technique in biventricular pacing. Very few data are reported about removal of LV pacing leads positioned in a CS branch. Aim of the study was to describe our experience with percutaneous extraction of LV pacing leads in order to evaluate feasibility and safety of this procedure. METHODS: we enrolled 392 patients who underwent a biventricular pacing implant. The indication for catheter removal was considered in case of definite diagnosis of infection and in some cases of lead dislodgement or diaphragmatic stimulation. LV lead extraction was first attempted by manual traction; in case of failure a locking stylet or locking stylet plus radiofrequency could be used. RESULTS: twelve of 392 patients implanted needed LV lead removal. The leads had been in place for 13.9 +/- 11.7 months. Extraction was indicated in 5 of them for LV lead dislodgement or diaphragmatic stimulation, and in 7 patients for lead infection. In all cases manual traction succeeded to remove the LV lead. In 7 cases of infection, the right atrial and ventricular leads were removed. The mean total procedure time was 69 +/- 22 min. No complications were observed. CONCLUSIONS: our study suggests that CS leads could be easily and safely removed without any complication, also when placed in a CS branch, at least for relatively young catheters.
Cohort Studies↗
A randomized evaluation of different approaches to coronary sinus venography during biventricular pacemaker implants.
AIM: Biventricular implantation procedures require contrast venography of the coronary sinus. The aim of our study was to evaluate the efficacy and safety of contrast venography obtained by direct manual contrast injection into the guiding catheter, compared with venography obtained after occlusion of the coronary sinus by a Swan-Ganz catheter. METHODS: Eighty-three patients were randomly assigned to direct or occlusive venography technique. The primary endpoint was complication rate. The secondary endpoints were rate of and time required for an adequate venography, total dose of contrast medium and total procedure time. RESULTS: Four dissections of the coronary sinus were observed with the occlusive venography technique group while no complications were observed with the direct venography technique group (p=0.04). Rate of adequate venography was similar in the two groups (p=NS). The time needed for coronary sinus venography and the total dose of contrast medium was significantly lower in the direct venography technique group compared with the alternative (p<0.0001 and p=0.003, respectively); the total procedure time was not significantly different between the two groups (p=NS). CONCLUSIONS: The direct venography technique shows a significantly lower incidence of complications and should be considered to be the first line approach to coronary sinus venography during biventricular pacemaker implantation.
Cardiac Pacing, Artificial↗
Use of a second buddy wire during percutaneous coronary interventions: a simple solution for some challenging situations.
The buddy wire technique, i.e. the use of a second 0.014 inch guide wire placed alongside the one employed to advance balloons and stents inside the coronary artery during percutaneous coronary intervention (PCI), may help in a series of procedural challenges during PCI. Indeed, by improving both the stability of the guiding catheter and the support for balloon and stent, a buddy wire use is sometimes the simplest way to accomplish a successful procedure. In this paper, we discuss technical aspects of some specific circumstances frequently encountered during PCI, in which a buddy wire may be helpful. These include: 1) The reduction of balloon slippage during angioplasty for in-stent restenosis; 2) insufficient back-up of the guiding catheter; 3) stenting of lesions located in vessels with proximal tortuosities/angulations; 4) stenting of lesions distally located in the vessel; 5) facilitation in the positioning of distal protection devices; 6) stenting of a lesion distally located from a previously implanted stent or from a coronary segment with both calcification and sharp bend; 7) PCI on coronary arteries with anomalous origin. Because of its simplicity, low cost, and availability, the use of a buddy wire should be considered when dealing with the aforementioned conditions during PCI procedures.
Angioplasty, Balloon, Coronary↗
Effect of primary percutaneous coronary intervention versus thrombolysis on ventricular arrhythmias and heart rate variability in acute myocardial infarction.
BACKGROUND: Several studies showed that thrombolysis reduces ventricular arrhythmias and improves heart rate variability (HRV) in patients with acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI) has recently become the treatment of choice for AMI, but it is still unknown whether it has favorable effects on these prognostic variables. METHODS: We studied a group of 44 consecutive AMI patients (39 males, 5 females, mean age 59 +/- 9 years) submitted to primary PCI and 93 consecutive AMI patients (80 males, 13 females, mean age 61.0 +/- 11 years) treated with thrombolytic therapy within 6 hours of symptom onset. All patients underwent 24-hour Holter recording before discharge. RESULTS: The number of premature ventricular beats and the prevalence of non-sustained ventricular tachycardia in the 24 hours were lower in the PCI group (162 +/- 474 and 9%, respectively) than in the thrombolysed group (334 +/- 1730 and 14%, respectively), but the difference did not achieve statistical significance (p = 0.62 and p = 0.58, respectively). There were also no significant differences in HRV variables between the two groups, although a lower proportion of PCI patients tended to have bottom quartile values of HRV variables. The favorable trend for arrhythmias and HRV in PCI patients, however, seemed to be related to a worse basal clinical profile of thrombolysed patients, including a higher prevalence of previous AMI (14 vs 2%, p = 0.065), diabetes (27 vs 18%, p = 0.14) and, in particular, a lower use of beta-blockers (35 vs 93%, p < 0.001). CONCLUSIONS: In this study, we failed to show any significant benefit of primary PCI compared to thrombolysis on ventricular arrhythmias and HRV in patients with ST-segment elevation AMI. The clinical implications of these findings deserve investigation in future studies.
Aged↗
Inflammation, genetics, and ischemic heart disease: focus on the major histocompatibility complex (MHC) genes.
BACKGROUND: Increasing data suggest that ischemic heart disease (IHD) shares several characteristics with common inflammatory diseases (such as rheumatoid arthritis), in which the pathogenetic role of inflammatory gene polymorphisms is well established. Variants in the genes for the major histocompatibility complex (MHC) molecules on the short arm of chromosome 6 show profound "linkage disequilibrium", leading to the formation of "haplotypes", i.e., frozen blocks of alleles travelling together through generations. DESIGN: We performed a review of published studies linking IHD with gene polymorphisms of the MHC molecules tumor necrosis factor (TNF)-alpha and -beta, the class II DR human leukocyte antigens, heat shock protein 70-1, hemochromatosis related gene, and complement C4. RESULTS: The emerging data are quite conflicting and do not provide definitive evidence for a role of these gene variants in the pathogenesis of IHD; a possible exception is the G252A and polymorphism in the TNF-beta gene (also known as lymphotoxin-alpha) which, in a comprehensive genome-scan linkage analysis of unrelated Japanese, but not in a smaller German population, was linked to myocardial infarction. However, some important biases appear, e.g. different study design and variable linkage disequilibrium among different populations. CONCLUSIONS: Preliminary positive results should encourage future studies to focus on clinical models of IHD with well-codified inflammatory components, using novel methods (such as haplotype analysis) to assess gene polymorphisms and their clinical effect.
Alleles↗
Platelet reactivity in response to mental stress in syndrome X and in stable or unstable coronary artery disease.
INTRODUCTION: Previous studies showed differences in platelet reactivity in response to exercise in patients with syndrome X (SX) and those with obstructive coronary artery disease (CAD). In this study, we investigated whether similar differences could be detectable in response to a mental stressful stimulus. MATERIALS AND METHODS: We studied 30 SX patients (60+/-8 years, 8 men), 20 patients with stable angina and angiographically documented CAD (SA, 66+/-8 years, 14 men), and 11 patients with unstable angina (UA, 67+/-8 years, 6 men). A control group of 22 healthy controls (50+/-7 years, 5 men) was also studied. All subjects underwent a mathematical mental stress test (MST) consisting of rapid consecutive subtractions of number 7 for a period of 5 min. A venous blood sample was collected at baseline and immediately after MST. Platelet reactivity was measured on flowing blood as time necessary to occlude a ring coated with collagen-adenosine diphosphate (ADP; closure time, CT), using the platelet function analyzer (PFA-100) system. RESULTS: At rest, CT was lower in UA patients (87+/-19 s) compared to controls (109+/-24 s, p=0.02) and SA patients (105+/-37 s, p=0.055), and also tended to be lower in SX patients (96+/-18 s) compared to controls (p=0.07). The CT response to MST differed significantly among groups (p=0.0009). At peak MST, CT did not change in controls (110+/-27 s, p=0.88), whereas it decreased in SA patients (96+/-29 s, p=0.003) and tended to decrease in UA patients (82+/-15 s, p=0.25). In contrast, a significant increase in CT with MST was shown in SX patients (103+/-21 s, p=0.007). CONCLUSIONS: Platelet reactivity is increased by MST in patients with CAD, whereas it paradoxically decreases in SX patients, which may constitute a protective effect against stress-induced events in these patients.
Aged↗
Insulin-like growth factor-1 as a vascular protective factor.
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Animals↗
Opposite patterns of left ventricular remodeling after coronary revascularization in patients with ischemic cardiomyopathy: role of myocardial viability.
BACKGROUND: In patients with ischemic cardiomyopathy, left ventricular (LV) remodeling is an important prognostic indicator. The precise relation between viable myocardium, revascularization, and ongoing or reversed remodeling is unknown and was evaluated in the present study. METHODS AND RESULTS: A total of 100 patients with ischemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability and LV geometry (volumes and shape). At a mean of 10.2 months and 4.5 years after revascularization, resting echocardiography was repeated to evaluate LV remodeling. Long-term follow-up (mean 5+/-2 years) data were obtained. According to dobutamine stress echocardiography, 44 patients (44%) were defined as viable (> or =4 viable segments) and 56 as nonviable. After revascularization, 40 patients (43%) had ongoing LV remodeling and 53 (57%) did not (in 7 patients who died early after revascularization, postoperative echocardiographic evaluation was not available). On multivariable analysis, the number of viable segments was the only predictor of ongoing LV remodeling (OR 0.60, 95% CI 0.48 to 0.75; P<0.0001). The likelihood of LV remodeling decreased as the number of viable segments increased. During the follow-up, reverse remodeling was present in viable patients, whereas in nonviable patients, LV volumes significantly increased, which indicates ongoing LV remodeling. At follow-up, viable patients also showed a persistent improvement of heart failure symptoms and fewer cardiac events than nonviable patients (P<0.05). CONCLUSIONS: In patients with ischemic cardiomyopathy, a substantial amount of viable myocardium prevents ongoing LV remodeling after revascularization and is associated with persistent improvement of symptoms and better outcome.
Aged↗
Comparison of long-term effect of coronary artery bypass grafting in patients with ischemic cardiomyopathy with viable versus nonviable left ventricular myocardium.
In this study, 63% of patients with a substantial amount of viable myocardium showed an increased left ventricular ejection fraction (LVEF) 12 +/- 3 months after coronary artery bypass grafting. In 93% of these patients, increased LVEF persisted at 4.5 +/- 1 years of follow-up. Conversely, in nonviable patients, LVEF did not increase at 12 +/- 3 months or at follow-up of 4.5 +/- 1 years.
Analysis of Variance↗
Assessment of systemic inflammation and infective pathogen burden in patients with cardiac syndrome X.
Inflammation plays a key role in coronary artery disease (CAD), but whether it is involved in the pathogenesis of syndrome X (SX) is not known. Thus, we assessed the presence of systemic inflammation in patients with SX and its possible relation to infections from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus. We studied 55 patients with SX (57 +/- 8 years old; 27 women), 49 with stable angina and obstructive CAD (56 +/- 8 years old; 24 women), and 60 healthy controls (57 +/- 11 years old; 24 women). Plasma levels of high-sensitivity C-reactive protein and interleukin-1 receptor antagonist were measured in all patients. Infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus was assessed in 43 patients with SX, 40 patients with CAD, and in 39 controls. Patients with SX had lower serum levels of C-reactive protein than did patients with CAD (4.06 +/- 6.8 vs 5.99 +/- 7.8 mg/L, p = 0.013) but higher levels of C-reactive protein than did controls (1.75 +/- 1.98 mg/L; p = 0.008). Plasma levels of interleukin-1 receptor antagonist were higher in patients with CAD (570 +/- 738 pg/ml) and patients with SX (494 +/- 677 pg/ml) than in controls (254 +/- 174, pg/ml; p = 0.0003 vs CAD and p = 0.013 vs SX) but did not differ significantly between patients with CAD or SX (p = 0.20). There were no differences across groups in the prevalence of infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus and in the prevalence of 1, 2, 3, and 4 infections (p = 0.99). Among patients with SX, no correlation was found between markers of inflammation and indexes of disease activity (angina episodes, exercise test results). Our data show evidence of increased low-grade systemic inflammation in patients with cardiac SX, which was unrelated to an increased infectious pathogen burden.
C-Reactive Protein↗
Widespread myocardial inflammation and infarct-related artery patency.
BACKGROUND: Diffuse coronary vascular inflammation is associated with acute coronary syndromes. However, it is unknown whether inflammation also occurs within the myocardium. Therefore, this study was aimed at assessing the presence of activated cells in unaffected remote myocardium of patients with acute myocardial infarction (AMI), in comparison to the peri-infarct region from the same cases, and in comparison to myocardial specimens from control hearts. METHODS AND RESULTS: Sixteen patients dying 1 to 12 weeks after AMI and 16 control subjects were selected at autopsy. Myocardial specimens were taken at remote unaffected viable regions and at peri-infarct regions in cases with AMI. Confocal microscopy was performed to measure the number of activated cells (DR+), T-lymphocytes (CD3+), and activated T-lymphocytes (CD3+/DR+). Activated cells and activated T-lymphocytes were found in remote unaffected regions in 11 of 16 cases (69%), in peri-infarct zone in all cases (100%), and in none of the control hearts (0%, P<0.001 versus others). A greater myocardial inflammatory burden in remote regions but not in peri-infarct regions was associated with persistent infarct-related artery occlusion (P<0.05). CONCLUSIONS: This study for the first time shows the presence of activated T-lymphocytes in remote unaffected myocardial regions in approximately two thirds of patients with recent AMI. Because these cells are associated with persistent infarct-related artery occlusion, our data may suggest that an antigenic stimulus present also in the myocardium triggers an immune response that may be critical to precipitate artery occlusion.
Aged↗