Giuseppe Steffenino

Plasma Activity and Insertion/Deletion Polymorphism of Angiotensin I–Converting Enzyme A Major Risk Factor and a Marker of Risk for Coronary Stent Restenosis

BACKGROUND Tissue proliferation is almost invariably observed in recurrent lesions within stents, and ACE, a factor of smooth muscle cell proliferation, may play an important role. Plasma ACE level is largely controlled by the insertion/deletion (I/D) polymorphism of the enzyme gene. The association among restenosis within coronary stents, plasma ACE level, and the I/D polymorphism is analyzed in the present prospective study. METHODS AND RESULTS One hundred seventy-six consecutive patients with successful, high-pressure, elective stenting of de novo lesions in the native coronary vessels were considered. At follow-up angiography, recurrence was observed in 35 patients (19.9%). Baseline clinical and demographic variables, plasma glucose and serum fibrinogen levels, lipid profile, descriptive and quantitative angiographic data, and procedural variables were not significantly different in patients with and without restenosis; mean plasma ACE levels (+/-SEM) were 40.8+/-3.5 and 20.7+/-1.0 U/L, respectively (P<.0001). Diameter stenosis percentage and minimum luminal diameter at 6 months showed statistically significant correlation with plasma ACE level (r=.352 and -.387, respectively P<.001). Twenty-one of 62 patients (33.9%) with D/D genotype, 13 of 80 (16.3%) with I/D genotype, and 1 of 34 (2.9%) with I/I genotype showed recurrence; the restenosis rate for each genotype is consistent with a codominant expression of the allele D. CONCLUSIONS In a selected cohort of patients, both the D/D genotype of the ACE gene, and high plasma activity of the enzyme are significantly associated with in-stent restenosis. Continued study with clinically different subsets of patients and various stent designs is warranted.

Coronary wedge pressure in relation to spontaneously visible and recruitable collaterals.

Coronary angiography demonstrates only collateral arteries that are already in use (spontaneously visible collaterals). Percutaneous transluminal coronary angioplasty (PTCA) provides an opportunity to uncover collaterals ready to become functional in case of occlusion of the recipient artery (recruitable collaterals). The incidence of recruitable collaterals and their relation to the distal pressure in the occluded artery (coronary wedge pressure) during a 30 sec or longer balloon occlusion was assessed in 57 coronary arteries of 49 patients undergoing PTCA for a proximal coronary stenosis or occlusion. Collateral to 75% of the arteries were present. Spontaneously visible collaterals were four times as frequent as recruitable collaterals. Coronary wedge pressure was significantly higher in arteries with spontaneously visible and recruitable collaterals (41 +/- 12 and 36 +/- 12 mm Hg, respectively) than in arteries without collaterals (18 +/- 4 mm Hg). A coronary wedge pressure of 30 mm Hg or higher was found exclusively in the presence of collaterals. Electrocardiographic changes during balloon occlusion were found more frequently with arteries without collaterals than with arteries with spontaneously visible or recruitable collaterals. Chest pain was more frequent in patients without collaterals or with recruitable collaterals than in those with spontaneously visible collaterals. Major in-hospital events occurred in three patients with collaterals, with a salutary influence of the collaterals in two. The coronary wedge pressure allows prediction of recruitable collaterals. Their clinical impact remains to be investigated in long-term studies on large patient populations.

Early Aggressive Versus Initially Conservative Treatment in Elderly Patients With Non–ST-Segment Elevation Acute Coronary Syndrome: A Randomized Controlled Trial

OBJECTIVES This study sought to determine the risk versus benefit ratio of an early aggressive (EA) approach in elderly patients with non-ST-segment elevation acute coronary syndromes (NSTEACS). BACKGROUND Elderly patients have been scarcely represented in trials comparing treatment strategies in NSTEACS. METHODS A total of 313 patients ≥ 75 years of age (mean 82 years) with NSTEACS within 48 h from qualifying symptoms were randomly allocated to an EA strategy (coronary angiography and, when indicated, revascularization within 72 h) or an initially conservative (IC) strategy (angiography and revascularization only for recurrent ischemia). The primary endpoint was the composite of death, myocardial infarction, disabling stroke, and repeat hospital stay for cardiovascular causes or severe bleeding within 1 year. RESULTS During admission, 88% of the patients in the EA group underwent angiography (55% revascularization), compared with 29% (23% revascularization) in the IC group. The primary outcome occurred in 43 patients (27.9%) in the EA group and 55 (34.6%) in the IC group (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.53 to 1.19; p = 0.26). The rates of mortality (HR: 0.87; 95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95% CI: 0.33 to 1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did not differ between groups. The primary endpoint was significantly reduced in patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to 0.80), but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to 3.70; p for interaction = 0.03). CONCLUSIONS The present study does not allow a definite conclusion about the benefit of an EA approach when applied systematically among elderly patients with NSTEACS. The finding of a significant interaction for the treatment effect according to troponin status at baseline should be confirmed in a larger size trial. (Italian Elderly ACS Study; NCT00510185).

Coronary wedge pressure: A predictor of restenosis after coronary balloon angioplasty

Coronary wedge pressure is the pressure recorded distal to a stenosis while the inflated balloon occludes the coronary artery during angioplasty. This pressure has been shown to reflect actual (visible) and potential (recruitable) collateral flow to the stenosed artery, distal to the angioplasty site. In 100 consecutive vessels (91 patients) for which coronary wedge pressure had been measured at the time of angioplasty, the long-term (7 +/- 3 months) angiographic results was evaluated. The overall angiographic restenosis rate was 37%. It was 52% (25 of 48) in arteries with a coronary wedge pressure greater than or equal to 30 mm Hg and 23% (12 of 52) in arteries with a coronary wedge pressure less than 30 mm Hg (p less than 0.01). The mean coronary wedge pressure was 30 +/- 10 mm Hg for vessels with restenosis and 26 +/- 9 mm Hg for those without restenosis (p less than 0.01). The prevalence of angiographically visible collateral flow was 42% and 29%, respectively (p = NS). Neither age, sex, presence of unstable angina, left ventricular function, number of diseased vessels nor initial and final transstenotic pressure gradient and degree of stenosis were significantly associated with the long-term outcome after angioplasty. Restenosis rate is significantly increased when coronary wedge pressure measured at the time of angioplasty is high (greater than or equal to 30 mm Hg). This suggests a negative influence of competitive collateral flow on long-term results of angioplasty.

Radiation exposure during diagnostic catheterization and single- and double-vessel percutaneous transluminal coronary angioplasty

Abstract Many previous studies exist on radiation exposure during diagnostic procedures. 1–4 Data on radiation exposure during percutaneous transluminal coronary angioplasty (PTCA) are scarce 5,6 and comparative data do not exist.

Angiographic follow-up after multivessel percutaneous transluminal coronary angioplasty

In 100 consecutive patients undergoing multivessel percutaneous transluminal coronary angioplasty (PTCA), dilation was attempted in 207 arteries. Primary success was achieved in 85 patients. Complications occurred in 8 patients: acute myocardial infarction in 5 and need for emergency coronary artery bypass surgery in 5. Control angiography was done in 77 of 85 patients (91%) with primary success at a mean of 12 +/- 6 months. Complete revascularization had been achieved in 59 patients and incomplete revascularization in 18. Angiographic restenosis was found in 39 of 77 patients (51%) and in 47 of 143 arteries (33%) at 9 +/- 7 months. The restenosis rate was 57% for chronic total occlusions (8 of 14) and 30% for stenoses (39 of 129). The restenosis rate was significantly higher for the left anterior descending coronary artery (40%) than for the left circumflex coronary artery (21%). However, the significance was lost after exclusion of chronic total occlusions. A higher residual stenosis and a high coronary wedge pressure were predictors for restenosis. Restenosis was clinically silent in 14 patients (18%). Repeat PTCA was done in 19 patients with recurrence and elective surgery in 8. Clinical follow-up was available in all patients at 24 +/- 12 months. Patients with incomplete revascularization had less favorable clinical follow-up results than patients with complete revascularization: 44% (8 of 18) vs 81% (48 of 59) were asymptomatic (p less than 0.005), and 28% (5 of 18) vs 5% (3 of 59) had undergone elective bypass surgery during follow-up (p less than 0.005). Most patients with restenosis after multivessel PTCA had only 1-vessel restenosis and only 7% had restenosis of all lesions.

The management of acute myocardial infarction in the cardiological intensive care units in Italy: the 'BLITZ 4 Qualità' campaign for performance measurement and quality improvement

Aim: To assess and promote compliance of Italian cardiological intensive care units (CCUs) with evidence-based guidelines for the management of acute myocardial infarction (MI). Methods and results: The process of diagnosis and treatment of MI was prospectively evaluated in 163 CCUs by use of 30 indicators during two enrolment phases, each followed by a feedback of both local and general performance. Overall, 5854 patients with ST-segment elevation MI (STEMI) and 5852 with non-ST-segment elevation MI (NSTEMI) were consecutively enrolled. The target for each indicator was defined as compliance with the relevant recommendations in ≥90% of suitable patients and it was met for nine (30%) and 10 (33.3%) indicators in the first and second phases, respectively. Regardless of target, a significant improvement in compliance was observed in the second phase in 10 out of 30 indicators (33.3%). Use of pre-hospital ECG, expedite delivery of reperfusion therapy, dosage of antithrombotic drugs, and non-pharmacological implementation of secondary prevention were often off target. Similar in-hospital mortality was observed in phases I and II, both in patients with STEMI (4.0 vs. 4.2%, p=0.79) and NSTEMI (1.8 vs. 2.4%, p=0.11). Overall, 30-day mortality were 5.7% for patients with STEMI and 3.4% with NSTEMI. Conclusions: Performance indicators can accurately weigh the whole process of diagnosis and treatment of patients with MI and monitor the improvements in the quality of care. In our large population of consecutive patients, satisfactory 30-day outcomes were observed despite suboptimal adherence to guidelines for some indicators of recognised prognostic relevance.

Causes of death in patients ≥75 years of age with non-ST-segment elevation acute coronary syndrome

The causes of death within 1 year of hospital admission in patients with non-ST-segment elevation acute coronary syndromes are ill defined, particularly in patients aged ≥75 years. From January 2008 through May 2010, we enrolled 645 patients aged ≥75 years with non-ST-segment elevation acute coronary syndromes: 313 in a randomized trial comparing an early aggressive versus an initially conservative approach, and 332, excluded from the trial for specific reasons, in a parallel registry. Each death occurring during 1 year of follow-up was adjudicated by an independent committee. The mean age was 82 years in both study cohorts, and 53% were men. By the end of the follow-up period (median 369 days, interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths were classified as cardiac in 94% of the cases during the index admission and 68% of the cases during the follow-up period. Eighty-six percent of the cardiac deaths were of ischemic origin. In a multivariate logistic regression model that included the variables present on admission in the whole study population, the ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p <0.001), hemoglobin level (hazard ratio 0.85, 95% confidence interval 0.76 to 0.94; p = 0.001), older age (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p = 0.010), and creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.97 to 0.99; p = 0.030) were the independent predictors of all-cause death at 1 year. In conclusion, within 1 year after admission for non-ST-segment elevation acute coronary syndromes, most deaths in patients aged ≥75 years have a cardiac origin, mostly owing to myocardial ischemia.

Plasma Lipoprotein(a) Is Not a Predictor for Restenosis After Elective High-Pressure Coronary Stenting

BACKGROUND Lipoprotein(a) is a risk factor for coronary artery disease. Although it has been implicated in restenosis after balloon angioplasty, its role in restenosis within coronary stents is unknown. The aim of the study was to assess the role of plasma lipoprotein(a) as a predictor for restenosis after elective coronary stenting. METHODS AND RESULTS Elective, high-pressure stenting of de novo lesions in native coronary arteries with Palmaz-Schatz stents was performed in 325 consecutive patients. Clinical, angiographic, and biochemical data were analyzed prospectively. Angiographic follow-up was performed at 6 months. Lipoprotein(a) levels were compared in patients with and without restenosis. Angiographic follow-up was obtained in 312 patients (96%); recurrence was observed in 67 patients (21.5%). No clinical or biochemical variable was associated with restenosis. Lipoprotein(a) level was 37.81+/-49. 01 mg/dL (median, 22 mg/dL; range, 3 to 262 mg/dL) in restenotic patients and 36.95+/-40.65 mg/dL (median, 22 mg/dL; range, 0 to 244 mg/dL) in nonrestenotic patients (P=NS). The correlations between percent diameter stenosis, minimum luminal diameter, and late loss at follow-up angiography and basal lipoprotein(a) plasma level after logarithmic transformation were 0.006, 0.002, and 0.0017, respectively. Multiple stents were associated with a higher incidence of restenosis (P=0.006), but biochemical data in these patients were similar to those treated with single stents. CONCLUSIONS The basal plasma level of lipoprotein(a) measured before the procedure is not a predictor for restenosis after elective high-pressure coronary stenting.

Vascular Access Complications after Cardiac Catheterisation: A Nurse-Led Quality Assurance Program

Background: Vascular access complications may be a cause of discomfort, prolonged hospital stay, and impaired outcomes in patients undergoing cardiac catheterisation. Aims: To assess vascular access complication in our patients with/without the use of closure devices as a first local benchmark for subsequent quality improvement. Methods: A nurse-led single-centre prospective survey of all vascular access complications in consecutive patients submitted to cardiac catheterisation during 4 months. Results: The radial and femoral access were used in 78 (14%) and 470 (83%), respectively, of 564 procedures, and a closure device was used in 136 of the latter. A haemathoma (any size) was isolated and uneventful in 9.6% of cases. More severe complications (haemoglobin loss > 2 g, need for blood transfusion or vascular repair) occurred in 1.2% of cases, namely: in none of the procedures with radial access, and in 0.4% and 2.4% of femoral diagnostic and interventional coronary procedures, respectively. During complicated (n = 40) vs uncomplicated (n = 172) transfemoral interventions, the activated coagulation time was 309 ± 83 vs 271 ± 71 s (p = 0.004), but the use of closure devices was similar. Conclusion: Severe vascular access complications in our patients were fewer than in most reports, and virtually absent in radial procedures. Vigorous anticoagulation was associated with increased complications in our patients, but closure devices were not. A new policy including both the use of the radial access whenever possible, and a less aggressive anticoagulation regimen during transfemoral interventions will be tested.