Placebo or trimetazidine (99m)Tc tetrofosmin myocardial SPECT and low-dose dobutamine echocardiography in hibernating myocardium.

BACKGROUND: Trimetazidine (TMZ) improves (99m)Tc sestamibi uptake in myocardial single photon emission tomography (SPECT). This study compared TMZ (99m)Tc tetrofosmin SPECT and low-dose dobutamine echocardiography (LDDE) as predictors of functional recovery of hibernating myocardium after coronary revascularization. METHODS: Thirty-one patients with prior myocardial infarction and left ventricular dysfunction underwent coronary angiography, LDDE, placebo SPECT and TMZ SPECT. Echocardiographic follow-up was obtained at 2/6 months; the clinical follow-up lasted 2 years. RESULTS: Twenty-three (74.2%) patients (195 dysfunctioning left ventricular segments) were revascularized. TMZ improved (99m)Tc tetrofosmin uptake (p = 0.0001) as well as LVEF at gated SPECT (p = 0.04). At 2-months, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated (LDDE 71.9, 78.7, 71, 79.5; placebo SPECT 66.2, 75.6, 65.4, 76.3; TMZ SPECT 79.2, 67.7, 61.6, 83.3, respectively). The specificity improved in placebo and TMZ SPECT (82.1 and 78.7%) at 6-months follow-up. Two patients (2/23) with hibernating myocardium treated with revascularization and three (3/4) treated medically died a cardiac death (p = 0.0016, log rank 12.89). None (0/4) without viability died during the 2-year follow-up (p = 0.6, log rank 0.28). CONCLUSIONS: The addition of TMZ to (99m)Tc tetrofosmin SPECT improved diagnostic accuracy. The importance of hibernating myocardium revascularization was confirmed.

Prognostic value of plasma brain natriuretic peptide, urea nitrogen, and creatinine in outpatients >70 years of age with heart failure.

This study analyzed the relevance of plasma brain natriuretic peptide (BNP) and echocardiography in predicting cardiovascular events in a large population >70 years old with heart failure (HF). Three hundred four outpatients with HF (51.6% men, mean age 78.6) underwent transthoracic echocardiography and plasma BNP testing shortly before hospital discharge. Echocardiography was intended to reveal systolic dysfunction (left ventricular [LV] ejection fraction [EF] <50%) or diastolic dysfunction (EF > or =50% and abnormalities of ventricular relaxation). During 6-month follow-up, all-cause death and readmission were assessed. One hundred seventeen patients had diastolic dysfunction with preserved systolic LV function, and 187 had systolic dysfunction. At 6-month clinical follow-up, 33 subjects (10.9%) had died, and 62 (20.4%) needed readmission for cardiac decompensation. In all patients, univariate logistic regression demonstrated significant correlations between age (r = 0.14, p = 0.01), plasma BNP (r = 0.36, p = 0.0001), the EF (r = 0.16, p = 0.003), urea nitrogen (r = 0.35, p = 0.0001), serum creatinine (r = 0.27, p = 0.0001), and New York Heart Association (NYHA) class (r = 0.35, p = 0.0001) and the occurrence of cardiovascular events. In patients with HF in NYHA class III or IV, a BNP cut-off level of 200 pg/ml identified different outcomes (BNP <200 pg/ml in 1 of 20 events vs BNP >200 pg/ml in 55 of 85 events, p = 0.0001). In patients with HF who were >70 years old, BNP, NYHA class, and renal function predicted adverse outcome. In patients with severe HF, BNP was better than NYHA class in predicting future events.

Estrogen receptor-alpha 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 alpha-estrogen receptor (alphaER) 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 alphaER 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 alphaER gene treated with coronary stent implantation have a higher risk of ISR than men.

Effect of angiotensin-converting enzyme inhibition on restenosis after coronary stenting.

The Plasma level of angiotensin-converting enzyme (ACE) has been identified as a major risk factor for restenosis after coronary stent implantation in selected patients; ACE inhibition may therefore contribute to prevent its occurrence. The effect of oral ACE inhibition at conventional doses was analyzed retrospectively in a series of 897 patients with ischemia who received >or=1 coronary stent on 998 lesions and underwent angiographic follow-up; no exclusion criteria were introduced in this analysis. The restenosis rate in 282 patients (31.4%) taking ACE inhibitors was 36.6% compared with 22.9% in 615 non-ACE-inhibited patients (p = 0.00001, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.45 to 2.59), and the late loss in minimum lumen diameter was 1.25 +/- 0.8 versus 0.96 +/- 0.8 mm, respectively (p = 0.0001). During univariate analysis, a negative effect of the drug on restenosis was observed in all subgroups of patients (i.e., hypertensives, diabetics, women, and patients with previous myocardial infarction). Similar effects were observed independently of the ACE gene insertion/deletion polymorphism. During multivariate analysis, ACE inhibition was confirmed as an independent risk factor for restenosis (OR 1.84, 95% CI 1.35 to 2.51, p = 0.0001). Other predictors were the implantation of multiple stents (OR 2.41, 95% CI 1.60 to 3.64, p <0.0001), diabetes (OR 2.34, 95% CI 1.61 to 3.41, p <0.0001), and vessel reference diameter before angioplasty (OR 0.51, 95% CI 0.38 to 0.69, p <0.0001). Although unexplained and apparently contradictory, our data suggest that the use of conventional oral doses of ACE inhibitors in a "real-world" population who underwent coronary stent implantation increases the incidence of in-stent restenosis. Such a finding does not negate the known clinical benefits of ACE inhibitors, but it may deserve attention when a patient treated with ACE inhibitors becomes a candidate for stent implantation.

Comparison of frequency of insulin resistance after coronary stenting in patients with type 2 diabetes mellitus with versus without coronary restenosis.

The large incidence of restenosis after coronary angioplasty in diabetic patients renders this procedure less effective than in nondiabetics, and insulin resistance could be a relevant cause of restenosis in such patients. This study assessed insulin resistance and biologic markers of metabolic control in type 2 diabetic patients treated with stented angioplasty. Seventy-four patients were studied prospectively. Biochemical determinations, insulin tolerance test results, and the rate constant for plasma glucose disappearance (K(itt)%) were obtained. The angiographic outcome of angioplasty was assessed by quantitative coronary analysis at baseline and at 6 months in 64 patients (86%). Patients with restenosis had smaller minimum luminal diameters after stenting (2.8 +/- 0.5 vs 3.04 +/- 0.5 mm, p = 0.05), were more often hypertensive (97% vs 79%, p = 0.02) and treated with angiotensin-converting enzyme inhibitors (53% vs 23%, p = 0.02), and had smaller K(itt)% (2.9 +/- 1.6%/min vs 3.7 +/- 1.4%/min, p = 0.04) and larger titers of growth hormone (1.36 +/- 1.5 vs 0.68 +/- 0.6 ng/ml, p = 0.02).

Predicting cardiac events with Tl201 dipyridamole myocardial scintigraphy in renal transplant recipients.

BACKGROUND: Renal transplant recipients should be screened for coronary artery disease. The purpose of this study was to evaluate the usefulness of thallium-201 dipyridamole myocardial perfusion single-photon emission computed tomography (SPECT) to predict major cardiac events in these patients. METHODS AND RESULTS: Eighty-two consecutive patients (61 males) in hemodialysis (HD) treatment, awaiting renal transplantation, underwent dipyridamole Tl-201 SPECT for pretransplant risk stratification. SPECT semiquantitative analysis showed a normal perfusion pattern in 52 patients (group A) and fixed defects in 9 (group B). Reversible perfusion defects were found in 21 (group C). Cardiac death, myocadial infarction, and unstable angina were sought as cardiac events. During a follow-up lasting 28.3 +/- 21.6 months, three patients of group A died for a non-cardiac cause. In group C, six patients (28.6%) had a cadiac event: one had a non-q wave myocardial infarction after renal transplantation; five were admitted with unstable angina. No cardiac events were observed in groups A and B (p = 0.0001). SPECT semiquantitative analysis showed that a summed difference score > or = 3 significantly increased the risk of cardiac events (odds ratio 4.5, C.I. 2.5-8.1). CONCLUSION: Cardiac events were only observed in HD patients with Tl-201 SPECT dipyridamole reversible defects (group C). A normal pattern or a fixed defect in Tl-201 dipyridamole SPECT in HD patients identified a good long-term prognosis.

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.

OBJECTIVES: The 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 RESULTS: Adenosine 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 < or = 35% was the only predictor of cardiac events (P = 0.01, log-rank 6.2). CONCLUSIONS: A 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.

[Should we use clopidogrel instead of ticlopidine in elective coronary angioplasty?]. / Dobbiamo sostituire la ticlopidina con il clopidogrel nelle angioplastiche coronariche elettive?

The use of ticlopidine in association with aspirin has reduced the incidence of subacute stent thrombosis to currently < 1% after coronary stent implantation. Clopidogrel, a more recently marketed thienopyridine derivative, has a lower incidence of side effects than ticlopidine. The use of clopidogrel in association with aspirin as compared to aspirin alone from the second through the sixth month after coronary angioplasty has been shown to reduce the 6-month incidence of major adverse cardiac events by 20-30%. Comparative studies about the use of ticlopidine and clopidogrel in patients undergoing stent implantation are scarce: these data are briefly reviewed. The conclusion is reached that, except for patients with non-ST-elevation acute coronary syndromes, there is at present no evidence that ticlopidine should be replaced with clopidogrel in all patients undergoing stent implantation; clopidogrel might be reserved for those patients who have shown side effects due to ticlopidine.

[Selection of contrast media for hemodynamic studies and limitation of the associated risk]. / Scelta del mezzo di contrasto per l'emodinamica e limitazione dei rischi connessi.

Both the choice of contrast media for use in the cardiac catheterization laboratory, and the practice for limiting patient damage, are relevant to the quality of health care. As part of our quality assurance program, and as a preliminary step to a critical reappraisal of our current protocols, an updated review has been made of existing evidence about contrast media for this use, and about measures to prevent adverse events. Consideration was also given to evidence-based measures or drug treatment in patients at risk for anaphylactoid reactions or with renal failure, as well as to the recommended course of action in diabetic patients receiving oral biguanide agents.

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

UNLABELLED: 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 < or = 45% underwent coronary angiography, rest basal myocardial SPECT (after 3-day placebo administration) and rest TMZ myocardial SPECT [after 3-day TMZ administration (60mg/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 < or = 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.

Effects of the addition of a low dose of spironolactone on brain natriuretic peptide plasma level and cardiopulmonary function in patients with moderate congestive heart failure.

BACKGROUND: The purpose of our study was to assess the effects of a low dose of spironolactone in patients with moderate congestive heart failure (CHF) on the plasma level of brain natriuretic peptide (BNP), echocardiographic left ventricular ejection fraction (LVEF), and cardiopulmonary function assessed by cardiopulmonary (CP) test. MATERIAL/METHODS: 51 CHF patients (74.5% males, mean age 60 years) underwent transthoracic echocardiography, CP test, and plasma BNP assay at the time of enrollment and after 6 months of standard therapy for CHF plus a low dose of spironolactone (group A). A control group (21 patients, group B) was treated using standard therapy only. All subjects were in NYHA class I-III and had LVEF < or = 40%. RESULTS: BNP concentration decreased significantly (from 45.7+/-57.4 pg/ml to 18.6+/-26.9 pg/ml at follow-up; p=0.01), and the NYHA class and LVEF improved (2.2+/-0.6 vs 1.7+/-0.5, p=0.0001; 27.7+/-7.2% vs 35.1+/-11%, p=0.001 respectively) in subjects in group A. In spite of clinical amelioration, peak oxygen consumption, oxygen pulse and anaerobic threshold in the CP test did not change significantly (16.6+/-5.7 ml/kg/min vs 17.1+/-5.3 ml/kg/min p=0.5; 8.8 +/- 4.3 ml/beat vs 9.5+/-3.6 ml/beat p=0.2; 0.75+/-0.2 ml/Kg/min vs 0.73+/-0.2 ml/Kg/min p=0.7). No differences were noticed in the control group. CONCLUSIONS: The addition of spironolactone reduced the BNP plasma level in patients with moderate CHF and increased LVEF. This therapy improved the NYHA class without modifying the functional parameters in the CP test.

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.