Progenitor cell mobilisation in patients with acute and chronic coronary artery disease.
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Biomedical subjects
Publications and source records attributed to A Gaspardone.
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BACKGROUND: Stent implantation for isolated stenosis of the proximal left anterior descending coronary artery (LAD) with preserved left ventricular function has been found to have a better clinical and angiographic outcome at one year than balloon angioplasty (PTCA). OBJECTIVE: To establish whether those results are maintained at five year follow up. METHODS: Patients were followed at least every six months. For those who died during follow up, data were obtained from medical records. MAIN OUTCOME MEASURES: Freedom from death, non-fatal myocardial infarction, cerebrovascular accident, and repeated target lesion revascularisation. Secondary end points were revascularisation in a remote region and freedom from angina. RESULTS: Follow up was complete in all patients. At five years, the primary end point was reached more often by patients randomised to stent implantation than to PTCA (80% v 53%; odds ratio (OR) 0.29 (95% confidence interval (CI) 0.13 to 0.69); p = 0.0034). In the PTCA group, 35% of patients underwent target lesion revascularisation v 15% in the stent group (OR 0.33, 95% CI 0.13 to 0.80; p = 0.014). There was a trend towards increased mortality in the PTCA group than in the stent group (17% v 7%; OR 0.36, 95% CI 0.10 to 1.21; p = 0.098). No significant differences were found between PTCA and stent groups for non-fatal myocardial infarction (8% v 5%; OR 0.58, 95% CI 0.13 to 2.54; p = 0.46) or cerebrovascular accident (2% v 0%). CONCLUSIONS: In patients with isolated stenosis of the proximal LAD, a five year clinical follow up confirmed a better outcome in those treated with stenting than with PTCA.
A 53 year old woman was referred for percutaneous coronary intervention because of a recent inferior myocardial infarction. During right coronary artery stent implantation, intermittent occlusion of the coronary side branch for the sinus node occurred, associated with intermittent sinus arrest and junctional escape rhythm. This led to speculation about the potential mechanisms for sinus node dysfunction. Degenerative fibrosis of nodal tissue is actually considered the most common cause of bradyarrhythmias. Yet, in everyday practice, no particular attention is usually paid to other potential pathogenic mechanisms such as coronary artery disease. This may be particularly true for elderly patients or patients with multiple risk factors. Thus, sinus node dysfunction may be an unrecognised marker of coronary artery disease.
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BACKGROUND: Because plaque inflammation may modulate coronary vasomotion, the association between systemic levels of C-reactive protein (CRP) and coronary vasoreactivity was assessed in patients with stable or unstable angina. METHODS AND RESULTS: In 31 patients with stable angina and 23 patients with unstable angina undergoing coronary angiography, minimal luminal diameter (MLD) of the culprit lesion was measured by quantitative coronary angiography at baseline, during the cold pressor test (CPT), and after intracoronary administration of nitroglycerin (NTG) and expressed as percent change from baseline. MLD of patients with unstable angina exhibited a greater reduction during CPT and a greater increase after NTG than did patients with stable angina (-17+/-14% versus -5+/-12%, P=0.0013, and 34+/-25% versus 8+/-20%, P<0.001, respectively). According to preprocedural serum levels of CRP, 36 patients had normal (</=0.5 mg/dL) and 18 patients had elevated CRP levels. MLD of patients with elevated CRP levels exhibited a greater reduction during CPT and a greater increase after NTG than of patients with normal CRP levels (-15+/-12% versus -7+/-14%, P=0.037, and 31+/-23% versus 13+/-25%, P=0.011, respectively). Both unstable angina and elevated CRP levels resulted in independent predictors of enhanced vasoreactivity at the multivariate analysis. CONCLUSIONS: This study confirms enhanced vasoreactivity of the culprit lesion in patients with unstable angina compared with those with stable angina. More importantly, it demonstrates that inflammatory mechanisms play a key role in modulating the reactivity of coronary atherosclerotic plaques and may partially account for the enhanced vasoreactivity of the unstable plaques.
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BACKGROUND: In the last decade, large-scale clinical trials have consistently shown that therapy with statins is of great benefit to patients with and at risk of developing coronary artery disease. We assessed, in a sample of patients with coronary artery disease in whom coronary angiography was indicated and hospitalized in the last 10 years, the use of statins at admission. METHODS: One hundred patients with stable coronary artery disease were randomly selected per year from 1991 to 2000. The final study population consisted of 1000 patients. The prescription of statins for > or = 6 months before hospital admission was determined from a hospital-wide clinical database. RESULTS: From 1995, the prevalence of patients treated with statins at hospital admission progressively increased. In 1991, only 2% of patients were treated with statins before hospital admission while in the year 2000, 38% of patients were receiving this treatment. The mean prevalence of patients treated with statins before and after 1995 was 3 vs 22% (p < 0.0001) respectively. The distribution of the demographic and clinical parameters and the prevalence of conventional cardiovascular risk factors were similar in patients treated or not treated with statins. CONCLUSIONS: After 1994, in coincidence with the publication of the results of clinical trials showing the benefit of statins in patients with coronary artery disease, the use of these drugs increased significantly. This finding suggests that the widespread diffusion of the results of the major clinical trials and of guidelines drawn up by medical associations have had a significant impact on statin prescription in patients with coronary artery disease. Nevertheless our data also indicate that, despite overwhelming evidence on the benefits of statin therapy, in current clinical practice cardiologists are not optimally utilizing lipid management and that statins are frequently prescribed without an appropriate analysis of risk factors.
BACKGROUND: The presence of endothelial dysfunction with increased endothelin-1 plasma concentrations in patients with cardiac syndrome X is still under debate. The aim of the present study was to evaluate the presence of endothelial dysfunction in patients with cardiac syndrome X. METHODS AND RESULTS: ++Endothelin-1 levels were evaluated with a sensitive radioimmunoassay with previous purification through reverse phase HPLC in 24 patients (3 men and 21 women, mean age 54+/-7 years) with typical angina, instrumental evidence of ischemia, and normal coronary angiograms both under baseline conditions and after oral glucose load (75 g D-glucose). We also measured plasma nitrite-plus-nitrate levels, a sharp index of endothelial nitric oxide production, and circulating concentrations of the soluble fraction of the endothelial adhesion molecule vascular cell adhesion molecule-1, a well-recognized marker of early endothelial dysfunction. Fourteen healthy subjects (1 man and 13 women, mean age 47+/-15 years) served as controls. There were no significant differences in baseline plasma endothelin-1 concentrations between patients and control subjects (0.55+/-0.34 versus 0.48+/-0.22 pg/mL, P=0.503). Plasma nitrite-plus-nitrate and soluble vascular cell adhesion molecule-1 concentrations were also similar between the 2 groups. After glucose ingestion, circulating endothelin-1 concentrations were significantly higher in patients with cardiac syndrome X than in control subjects (P<0.03 at 60, 90, and 120 minutes). CONCLUSIONS: Our findings show that no basal endothelial damage is present in patients with cardiac syndrome X. Nevertheless, increased responsiveness of endothelin-1 to glucose loading suggests that patients with cardiac syndrome X present an increased susceptibility to releasing endothelin-1 under stressful circumstances.
This study was aimed at establishing the relation between baseline C-reactive protein levels and 12-month outcome in patients with unstable angina successfully treated with coronary artery stent implantation. Our results suggest that in patients with unstable angina and 1-vessel coronary disease successfully treated with coronary artery stent implantation, normal baseline serum levels of C-reactive protein identify a subgroup of patients at low risk of cardiac events during follow-up.
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OBJECTIVE: To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%. PATIENTS AND METHODS: In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat. RESULTS: Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.
BACKGROUND: Classic experimental studies have shown that in the presence of a flow-limiting coronary artery stenosis, myocardial ischemia during metabolic or pharmacological arteriolar vasodilation causes wall motion abnormalities, which precede electrocardiographic (ECG) changes in the myocardial regions supplied by the stenotic branch. The aim of this study was to establish whether in patients with chronic stable angina the regional distribution of wall motion changes and sequence of ischemic events are similar to that observed in experimental models, as currently believed. METHODS: The study population consisted of 20 men and 4 women (mean age 59 +/- 10 years) who were recruited on the basis of the following criteria: 1) a history of chronic stable angina without clinical and instrumental evidence of previous myocardial infarction; 2) reproducible positive exercise tests for ECG myocardial ischemia and anginal pain; 3) angiographically normal left ventricular function; 4) isolated stenosis of the left anterior descending coronary artery (LAD). Patients underwent continuous 12-lead ECG and echocardiographic monitoring during dipyridamole infusion. RESULTS: During dipyridamole infusion 3 patients (13%) did not develop echocardiographic changes, ECG changes or angina, 14 (58%) exhibited ECG changes, 18 (75%) lamented angina and 16 (67%) developed echocardiographic changes. In 5 of these 16 patients (31.5%) echocardiographic changes occurred in LAD-dependent territories only, in 5 they occurred in non-LAD-dependent territories only (31.5%) and in 6 (37%) they occurred in both LAD- and non-LAD-dependent territories. A total of 14 patients exhibited both echocardiographic and ECG changes and/or angina. In 6 of these 14 patients (43%) echocardiographic changes were the first ischemic events; in the remaining 8 patients (57%) ECG changes and/or angina were the first ischemic events. CONCLUSION: In the majority of patients during dipyridamole infusion regional wall motion changes occur in territories supplied by non-stenotic coronary artery branches; they are probably caused, therefore, by distal vessel dysfunction. Furthermore, the sequence of ischemic events is different in individual patients. These findings indicate that in stable angina the mechanisms of ischemia are multiple and that the link between coronary stenoses and myocardial ischemia is very elusive.
BACKGROUND: To establish whether the adaptation to ischemia observed in humans during percutaneous transluminal coronary angioplasty (PTCA) after repeated balloon inflations, i.e. a clinical correlate of ischemic preconditioning, is preserved in elderly patients. METHODS: We studied 53 consecutive patients undergoing successful angioplasty for an isolated stenosis of a major epicardial coronary artery. On the basis of age, patients were separated into terciles: patients in the lower and middle terciles were grouped together (Group 1, adult patients, n = 24, mean age 50 +/- 6 years) and compared with those in the upper tercile (Group 2, elderly patients, n = 29, mean age 68 +/- 3 years). Intracoronary electrocardiogram was obtained at the end of the first two balloon inflations. Collateral recruitment during repeated balloon inflations was assessed by using an intracoronary Doppler guide wire (23 patients) or by using an intracoronary pressure guide wire (30 patients). RESULTS: In Group 1, ST-segment changes during the second inflation were significantly less than those at the end of the first inflation (6 +/- 3 vs 13 +/- 5 mm, p < 0.001). Similarly, in Group 2, ST-segment changes during the second inflation were significantly less than those at the end of the first inflation (6 +/- 4 vs 13 +/- 6 mm, p < 0.001). In both groups, collateral recruitment did not change from the first inflation to the second inflation (p = 0.1). CONCLUSIONS: Our study confirms that adaptation to ischemia during repeated balloon inflations in the setting of PTCA is independent of collateral recruitment and, therefore, is mainly due to ischemic preconditioning. More importantly, our study indicates that ischemic preconditioning is preserved in elderly patients.
This report describes the different clinical and instrumental manifestations of coronary ischemia in a patient with left main coronary artery atresia. Exercise test and thallium-201 perfusion scintigraphy during isometric exercise test were negative for angina and electrocardiographic changes. Conversely, dipyridamole infusion caused severe angina, marked ST-segment changes and diffuse thallium-201 uptake abnormalities. This peculiar anatomical condition offers the opportunity of high-lighting the role played by the microcirculation in determining myocardial ischemia.
We performed a prospective study to establish the efficacy of coronary stent placement in a highly selected group of patients with focal coronary artery spasm in whom anginal attacks could not be prevented by full medical therapy. The results of this study indicate that intracoronary stent placement may represent an alternative and feasible treatment for patients with vasospastic angina refractory to aggressive medical therapy.
The aim of the present study was to establish whether exercise-induced ischemia triggers the second window of protection in 15 patients with coronary artery disease undergoing 2 consecutive treadmill exercise tests and a third test 24 hours later. Our findings confirm that a first exercise-induced ischemic challenge induces the early phase of preconditioning but not the late phase, thus suggesting that either a late protective effect of preconditioning does not exist in the setting of demand ischemia or, if it exists, it must be weaker than the early protective effect.
BACKGROUND: The impairment of flow reserve of the left anterior descending coronary artery in the early postoperative period in patients receiving a left internal thoracic artery graft has been related to the effects of cardiopulmonary bypass. Indeed, the late improvement in flow has been attributed to a late increase in left internal thoracic artery diameter. METHODS: We evaluated 12 patients who underwent minimally invasive direct coronary artery bypass surgery with the internal thoracic artery used to graft an occluded left anterior descending artery without extracorporeal circulation. Early and 6 months after the operation, patients underwent a second angiogram of the left internal thoracic artery graft and assessment of coronary flow reserve by use of an intracoronary 0.014-inch Doppler guide wire. RESULTS: At the late study, coronary flow reserve had increased compared with the early postoperative data from 1.8 +/- 0.4 (standard deviation) to 2.5 +/- 0.6 (P =.002) because of a significant decrease in baseline averaged peak velocity (32.4 +/- 6.2 vs 21.3 +/- 6.4 cm/s, P =.002), whereas the hyperemic values were similar (51 +/- 6 vs 53.7 +/- 21.9 cm/s, P =.6). The diameters of the thoracic artery (2.1 +/- 0.3 vs 2.2 +/- 0.3 mm, P =. 7) and the left anterior descending coronary artery (1.8 +/- 0.1 vs 1.8 +/- 0.2 mm, P =.5), as well as myocardial oxygen consumption (106 +/- 14 vs 101 +/- 16 mm Hg. beats/min. 10(-2), P =.5), were unchanged. CONCLUSIONS: Our findings suggest that the late improvement in coronary flow reserve is independent of the diameter of the graft and probably reflects an early distal coronary vessel dysfunction, which normalizes with time.
OBJECTIVES: We attempted to establish whether naloxone, an opioid receptor antagonist, abolishes the adaptation to ischemia observed in humans during coronary angioplasty after repeated balloon inflations. BACKGROUND: Experimental studies indicate that myocardial opioid receptors are involved in ischemic preconditioning. METHODS: Twenty patients undergoing angioplasty for an isolated stenosis of a major epicardial coronary artery were randomized to receive intravenous infusion of naloxone or placebo during the procedure. Intracoronary electrocardiogram and cardiac pain (using a 100-mm visual analog scale) were determined at the end of the first two balloon inflations. Average peak velocity in the contralateral coronary artery during balloon occlusion, an index of collateral recruitment, was also assessed by using a Doppler guide wire in the six patients of each group with a stenosis on the left anterior descending coronary artery. RESULTS: In naloxone-treated patients, ST-segment changes and cardiac pain severity during the second inflation were similar to those observed during the first inflation (12+/-6 vs. 11+/-7 mm, p = 0.3, and 58+/-13 vs. 56+/-12 mm, p = 0.3, respectively), whereas in placebo-treated patients, they were significantly less (6+/-3 vs. 13+/-6 mm, p = 0.002 and 31+/-21 vs. 55+/-22 mm, p = 0.008, respectively). In both naloxone- and placebo-treated patients, average peak velocity significantly increased from baseline to the end of the first inflation (p = 0.04 and p = 0.02, respectively), but it did not show any further increase during the second inflation. CONCLUSIONS: The adaptation to ischemia observed in humans after two sequential coronary balloon inflations is abolished by naloxone and is independent of collateral recruitment. Thus, it is due to ischemic preconditioning and is, at least partially, mediated by opioid receptors, suggesting their presence in the human heart.