Eugenio Uslenghi

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.

Estrogen Receptor-α Polymorphisms and Angiographic Outcome After Coronary Artery Stenting

Objective—Because of the receptor-mediated antiproliferative effects of estradiol on vascular smooth muscle cells, our study aimed at identifying a role of PvuII and XbaI polymorphisms of the &agr;-estrogen receptor (&agr;ER) gene in the occurrence of restenosis after coronary stent implantation (in-stent restenosis [ISR]). Methods and Results—In 858 patients (148 women), 955 lesions were treated with stent implantation, and the PvuII C/T and XbaI G/A polymorphisms of the &agr;ER gene were determined. Quantitative angiography was performed before and after stenting and at 6-month follow-up. The allelic frequencies were similar between sexes (C/T allele, 0.43/0.57 and 0.44/0.56; P =0.9; G/A allele, 0.35/0.65 and 0.38/0.62; P =0.8; in women and men, respectively). A significantly higher ISR rate in women than in men homozygous for the T-allele of the PvuII polymorphism (42.6% versus 26.9%, P =0.03) or the G-allele of the XbaI polymorphism (41.2% versus 19.4%, P =0.04) was observed. At multivariate analysis, T/T genotype was the only independent predictor of ISR in women but not in men (odds ratio, 1.5; 95% CI, 1.0 to 2.1; P =0.03). XbaI polymorphism was no longer associated with ISR in both sexes. Conclusions—Women homozygous for the T-allele of the PvuII polymorphism of the &agr;ER gene treated with coronary stent implantation have a higher risk of ISR than men.

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.

Association study of the I/D polymorphism and plasma angiotensin-converting enzyme (ACE) as risk factors for stent restenosis

The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95%). Restenosis rates among genotypes were 31.2% DD, 25.5% ID and 28.8% II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7+/-18.6 units/l compared with 22.8+/-12.8 units/l; P=0.0001) and a strong independent predictor of ISR [OR (odds ratio)=3.70; 95% CI (confidence interval), 2.40-5.71; P<0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR=0.16; 95% CI, 0.04-0.69; P=0.014; and patients with AMI, OR=0.21; 95% CI, 0.061-0.749; P=0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7% DD, 24.3% ID and 17.6% II (P=0.02; DD compared with non-DD OR=1.57; 95% CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.

Coronary stenting after unsuccessful emergency angioplasty in acute myocardial infarction: results in a series of consecutive patients.

Nineteen consecutive procedures of coronary stenting were attempted in 70 consecutive patients (27%) with evolving myocardial infarction due to threatened vessel reocclusion after primary (16 cases) or rescue (3 cases) angioplasty. Two patients were in cardiogenic shock. Stent delivery was successful in 18 patients, with a Thrombolysis in Myocardial infarction flow grade 3; residual diameter stenosis and minimum luminal diameter were 19% +/- 11% and 2.96 +/- 0.62 mm, respectively. After the procedure, heparin was continued for 4 days and 250 mg ticlopidine twice a day for 1 month. Acute stent occlusion occurred in one patient 1 hour after the procedure and was successfully treated with emergency repeat angioplasty. Subacute stent occlusion occurred 6 days after the procedure in one patient, with multivessel coronary disease and a suboptimal stent result. He had been referred for surgery, and emergent coronary artery bypass was performed. Coronary bypass surgery was performed in another patient before discharge because of severe multivessel disease. Persistent cardiogenic shock and new myocardial infarction in another location were the causes of death in two patients, 3 and 10 days after the procedure, respectively. Fifteen patients were discharged with a patient infarct vessel and without reinfarction or need for coronary bypass surgery. One patient had repeat angioplasty for intrastent restenosis at 3 months. The remaining 14 patients were free from new coronary events 4 +/- 2 months after the procedure. Although acute myocardial infarction is generally considered a contraindication to the use of coronary stents, stents may play a role in increasing the rates of successful infarct artery reperfusion.

The diagnosis of coronary artery disease in Hypertensive patients with chest pain and complete left bundle branch block: Utility of adenosine Tc-99m tetrofosmin SPECT

Purpose Hypertensive patients with complete left bundle branch block who experience chest pain present special problems in the radionuclide diagnosis of coronary artery disease (CAD). The aim of this study was to assess the utility of Tc-99m tetrofosmin SPECT for the diagnosis of CAD in 35 hypertensive patients with left bundle branch block hospitalized for chest pain. Materials and Methods Images were analyzed semiquantitatively for the presence of both fixed or reversible perfusion defects (method A) or only reversible defects (method B) in the distribution of the left anterior descending artery (LAD) territory. Perfusion defects observed in the territory of any other coronary artery were always considered. Thirty-five patients without infarction underwent adenosine Tc-99m tetrofosmin SPECT, transthoracic echocardiography, and coronary angiography. Results The mean left ventricular ejection fraction was calculated as 39.9% ± 11.6%, and the prevalence of CAD was 29%. The sensitivity of SPECT was identical for the two methods at 89%. The specificity increased 19% with method A and 54% with method B. The positive predictive value remained unsatisfactorily low with both methods (27% for method A and 40% for method B), and the negative predictive value improved from 83% with method A to 93% with method B. Conclusions Only reversible perfusion defects in the LAD territory should be considered significant for CAD, and these patients should undergo coronary angiography. Reversible or fixed perfusion defects in the left circumflex and right coronary artery territories should be evaluated according to other clinical parameters (global left ventricular ejection fraction, extension of perfusion defects). The highly negative predictive value of adenosine SPECT could help in the exclusion of CAD.

The usefulness of adenosine 99mTc tetrofosmin SPECT for the diagnosis of left anterior descending coronary artery disease in patients with chest pain and left bundle branch block.

ObjectivesThe aim of this study was to assess the usefulness of 99mTc tetrofosmin single photon emission computed tomography (SPECT) for the diagnosis of left anterior descending (LAD) coronary artery disease in 60 subjects with left bundle branch block (LBBB) admitted for chest pain. Methods and resultsAdenosine 99mTc tetrofosmin SPECT, transthoracic echocardiogram and coronary angiography were performed, by protocol, in 60 non-infarcted consecutive patients. The mean left ventricular ejection fraction (LVEF) was 41.6±10.8%. A significant angiographic disease of the LAD was found in 15 (25%) patients. The sensitivity and the specificity of SPECT was found to be 75% and 89%, respectively; the positive predictive value (PPV) was 70% with a negative predictive value (NPV) of 91%. During the adenosine infusion the QRS complex width reduced from 131.3±29.6 ms to 125.5±28.6 ms in the patients without LAD involvement (P=0.008) but remained unchanged in LAD disease patients (P=0.1). Combining SPECT information and QRS analysis the sensitivity increased to 87% with unchanged specificity, the PPV was 74% and the NPV resulted 95%. At 2-year follow-up 13 (22%) patients experienced a cardiac event. Using Kaplan–Meier analysis, an LVEF of≤35% was the only predictor of cardiac events (P=0.01, log-rank 6.2). ConclusionsA quarter of patients with LBBB complaining of chest pain had LAD coronary disease. The highly negative predictive value of adenosine SPECT could help in the exclusion of LAD disease, especially when the SPECT image is combined with the QRS analysis.

The acute administration of trimetazidine modified myocardial perfusion and left ventricular function in 31 patients with ischaemic ventricular dysfunction.

Trimetazidine (TMZ) increases the mithocondrial oxidative metabolism and improves Tc-99m sestamibi uptake in myocardial single photon emission tomography (SPECT). The aim of this study was to evaluate whether the acute administration of TMZ improved myocardial perfusion and modified left ventricular ejection fraction (LVEF) in ischaemic left ventricular impairment. Methods: Thirty-one patients (23 males, age 66 years) with prior myocardial infarction (6 months) and echocardiographic LVEF ≤ 45% underwent coronary angiography, rest basal myocardial SPECT (after 3-day placebo administration) and rest TMZ myocardial SPECT [after 3-day TMZ administration (60 mg/die)]. The left ventricle was analysed in 16 segments. The summed placebo score (SPS) and the summed TMZ score (STS) were calculated with a 5-point scale (from 0 = normal uptake to 4 = absent uptake) by two blinded operators. The GATED Tc-99m SPECT was always provided. Results: After TMZ administration GATED LVEF improved from 26.5 ± 9.7% to 29.1 ± 11.3%(p= 0.04) and left ventricular end-systolic volume (LVESV) was reduced from 90.2 ± 40.7 to 85.6 ± 39.2 ml/mq (p= 0.006). Similarly the addition of TMZ to myocardial SPECT significantly reduced the STS compared to SPS (21.5 ± 11 vs. 26.6 ± 10.5 p= 0.0001). Eleven patients (35.5%) had an echocardiographic LVEF ≤ 30%; in these patients who had severe ventricular dysfunction, GATED LVEF and LVESV did not change after TMZ (20.2 ± 5.7% vs. 21 ± 6.9%p= 0.6; 116.7 ± 35.3 ml vs. 112.6 ± 32.3 ml p= 0.08, respectively). Conclusion: In comparison with placebo, the addition of TMZ to myocardial Tc-99m tetrofosmin SPECT improved myocardial perfusion and LVEF, reducing LVESV. These effects were lost in patients with more severe ventricular dysfunction.

Can ACE Inhibitors Promote Detrimental Vascular Effects After Percutaneous Injury

To the Editor: Zhuo et al1 reported interesting observations in vivo about the effects of angiotensin-converting enzyme (ACE) inhibition with perindopril on plasma ACE levels and cellular expression of ACE, AT1 receptors, and nitric oxide synthase (NOS) isoforms in human blood vessels. Oral ACE inhibition at conventional doses (perindopril 4 mg/d) decreased plasma ACE activity by 70% and vascular ACE immunoactivity to 65% of control subjects detected by immunocytochemistry, and increased endothelial NOS (eNOS) and inducible NOS (iNOS) expression in the vascular wall. However, the authors also observed a dramatic 80% increment of the AT1 receptor binding in vascular smooth muscle cells, which might increase the potential of these receptors to counterbalance the beneficial effects of suppressed angiotensin II formation if AT1 receptors were activated by alternative sources of angiotensin II. Whether the overexpression of AT1 receptors may somehow limit, or even reverse, the beneficial effects of ACE inhibitors in specific clinical situations of vascular disease has stimulated the following comments. So far, mostly beneficial vascular effects have been reported in patients treated with ACE inhibitors.2,3 However, 2 recent publications have shown that oral administration …

PREVALENCE OF LATE POTENTIALS AFTER MYOCARDIAL INFARCTION TREATED WITH SYSTEMIC THROMBOLYSIS OR PRIMARY PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY

The term cardiomyopathy was probably used for the first time in 1957, when W. Bridgen [1] described the diseases of the myocardium of “non-coronary ” etiology. Previously, a variable terminology had been used for these diseases, such as “myocardosis ” /“cardiac myopathy ”, “myocarditis ” etc.