[Show abstract][Hide abstract] ABSTRACT: Angiographic and electrocardiographic (ECG) indexes of microvascular obstruction (MVO) have been described. We aimed at assessing by cardiac magnetic resonance (CMR) anatomical features underlying concordance between them.
Journal of Cardiovascular Medicine 07/2014; · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:Pre-infarction angina (PIA) has been shown to reduce the microvascular obstruction (MVO) rate in patients with ST-segment elevation myocardial infarction (STEMI). We sought to evaluate the potential modulator role of cardiovascular risk factors (CRFs) on this protective effect.Methods and Results:Two hundred patients with STEMI were enrolled. PIA was defined as typical chest pain within the 48 h preceding STEMI onset. Angiographic MVO was defined as TIMI flow grade <2 or TIMI flow 3 with myocardial blush grade <2; electrocardiographic (ECG) MVO was defined as ST-segment elevation resolution <70%. Common CRFs were collected. In the absence of hypertension, both angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas, in the presence of hypertension, they were similar in both study groups (P for interaction=0.01 and P=0.014, respectively). Among nonsmokers, angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas within smokers, they were similar in both study groups (P for interaction=0.037 and P=0.037, respectively). In the absence of dyslipidemia, the angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas within dyslipidemic patients, they were similar in both study groups (P for interaction=0.012 and P=0.04, respectively).Conclusions:The protective effect of PIA on MVO is blunted by CRFs.
[Show abstract][Hide abstract] ABSTRACT: Our study aimed to elucidate mechanisms underlying discordance between fractional flow reserve (FFR) and hyperemic stenosis resistance (hSR) in some patient subsets. To do this, we enrolled 30 consecutive patients with stable angina or non-ST elevation myocardial infarction (non-STEMI) and with a nonculprit intermediate coronary lesion (40% to 70%) by coronary angiography. We measured aortic pressure, flow velocity, and pressure distal to lesion simultaneously at basal level and during adenosine-induced (fixed intracoronary dose of 120 μg) hyperemia using a dual-sensor-equipped guidewire. Microvascular resistance (MR; pressure distal to lesion/flow velocity, mm Hg/cm/s) and variation (Δ) in MR levels were calculated both at baseline and after hyperemia, whereas FFR (cutoff <0.80) and hSR [(aortic pressure - pressure distal to lesion)/flow velocity, cutoff >0.80 mm Hg/cm/s] were assessed after intracoronary adenosine. Twenty-three patients (76.7%) showed concordance and 7 patients (23.3%) showed discordance between FFR and hSR (all cases with FFR >0.80 and hSR >0.80). Discordant patients presented more frequently with non-STEMI (85.7% vs 39.1%, p = 0.04), significantly higher C-reactive protein serum levels (median [interquartile range] 5.9 [5.1 to 6.8] vs 4.9 [3.7 to 6.2] mg/L, p = 0.007), and lower ΔMR (p = 0.03) values compared with concordant patients. In conclusion, patients with non-STEMI and those with increased C-reactive protein levels show a lower reduction in MR after intracoronary adenosine-induced hyperemia, leading to FFR underestimation.
The American journal of cardiology 05/2014; 113(9):1461-7. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Persistent oxidative stress may play a key role in microvascular obstruction (MVO). We aimed at assessing the role of platelet gp91phox (NOX2), the catalytic subunit of NADPH oxidase in MVO.
We enrolled 40 patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention within 12 h from symptoms onset, either with angiographic MVO (n=20) or good angiographic myocardial reperfusion (MR) (n=20). Angiographic MVO was defined as a final thrombolysis in myocardial infarction (TIMI) flow ≤2 or TIMI flow of 3 with myocardial blush grade <2. NOX2 and isoprostanes (8-iso-PGF2α) levels, as assessed by enzyme-linked immunoadsorbent assay (ELISA) or by an enzyme immunoassays, respectively, were measured on admission, at 24 h and pre-discharge.
NOX2 levels increased from baseline to pre-discharge in patients with angiographic MVO (20.25 (15-24.75) pg/ml vs 25.50 (17-29.25) pg/ml, p=0.02), but not in MR patients (p=0.45), with a significant interaction between baseline and pre-discharge levels among the two groups (p=0.04). The levels of 8-iso-PGF2α showed a trend to increase from baseline to pre-discharge in angiographic MVO patients (295 (183.50-389.25) pmol/l vs 322 (206-370) pmol/l, p=0.06), but not in patients with MR (p=0.56), with a trend for interaction between baseline and pre-discharge levels among the two groups (p=0.09).
Patients with MVO, but not those with myocardial reperfusion, have a sustained increase of NOX2 and 8-iso-PGF2α. Therapies targeting NOX2 or high dosage antioxidants should be tested for MVO prevention and treatment.
European heart journal. Acute cardiovascular care. 12/2013; 2(4):379-88.
[Show abstract][Hide abstract] ABSTRACT: Parvovirus (PV) B19 DNA is detected in endothelial cells and may cause endothelial dysfunction which is involved in in-stent restenosis. We aimed at performing an exploratory analysis that evaluated if PVB19 DNA at the culprit coronary stenosis would be associated with an increased rate of major adverse cardiac events (MACE) after coronary stenting.
Consecutive patients undergoing stent implantation for stable or unstable coronary artery disease were enrolled. Serology for PVB19 infection and presence of DNA for PVB19 on balloons used for predilatation were assessed in all patients. MACE rate, as a composite of cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularization (TLR) was obtained at twenty-four month follow-up. Adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for variables associated with MACE.
One-hundred and nine patients [age 66±10, male sex 89 (82%)] were enrolled. At 24 month follow-up, 18 patients experienced a MACE. Two patients (2%) experienced MI, while 16 patients (15%) experienced clinically driven TLR. At multiple Cox regression analysis, the presence of PVB19 DNA on the balloon and the use of bare-metal stents were independent predictors of MACE [HR 3.30, 95% CI (1.12-10.08), P=0.03 and HR 4.19, 95%CI (1.60-10.94), P=0.003].
PVB19 DNA detected on the balloon used for dilatation of coronary stenosis before stent implantation is associated with MACE rate at follow-up, mainly due to clinically driven TLR. The results of this exploratory analysis should be confirmed in a larger population. This article is protected by copyright. All rights reserved.
European Journal of Clinical Investigation 11/2013; · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: No-reflow after primary percutaneous coronary intervention (pPCI) may be reversible. 40 patients undergoing pPCI were evaluated by assessing either improvement or lack of changes regarding angiographic and electrocardiographic indexes of no-reflow between admission and pre-discharge. Myeloperoxidase (MPO; in nanograms per milliliter), C-reactive protein (CRP; in milligrams per liter), endothelin-1 (ET-1; in nanograms per milliliter), angiopoietin-2 (Ang-2, in picograms per milliliter), and their pre-discharge/basal values variations (Δ) were related to no-reflow evolution. ΔMPO and ΔCRP were greater in patients with sustained no-reflow or lack of ST-segment resolution (STR) as compared with those with reversible no-reflow or lack of STR (p = 0.033, p = 0.04, p < 0.001, and p = 0.001, respectively), whereas ΔET-1 was similar in the two groups. ΔAng-2 was greater in patients with sustained no-reflow or lack of STR as compared with those with reversible no-reflow or lack of STR (p = 0.01 and 0.044, respectively). Bigger ΔMPO, ΔCRP (increasing levels), and ΔAng-2 (decreasing levels) are associated with sustained no-reflow, thus they might have a role in no-reflow evolution.
Journal of Cardiovascular Translational Research 09/2013; · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laser atherectomy might decrease procedural complications during percutaneous coronary intervention (PCI) of degenerated saphenous vein grafts (SVGs) in case of unstable or thrombotic lesions because of its ability to debulk and vaporize thrombus. We aimed at prospectively evaluating the safety and efficacy of excimer laser coronary angioplasty (ELCA) as a primary treatment strategy in consecutively unstable patients undergoing PCI of degenerated SVG lesions. Seventy-one consecutive patients with non-ST elevation acute coronary syndrome (mean age 69 ± 10 years, 66 men [89%]) undergoing PCI of degenerated SVG were enrolled in a prospective case-control registry, using 2 different distal protection devices (DPDs; FilterWire EZ [Boston Scientific, Natick, Massachusetts; n = 24] and SpiderRX [Ev3, Plymouth, Minnesota; n = 23]) or ELCA (n = 24). Primary end points of the study were incidence of angiographic microvascular obstruction (Thrombolysis In Myocardial Infarction flow grade of <3 or Thrombolysis In Myocardial Infraction flow grade of 3 with myocardial blush grade 1 to 2) and incidence of type IVa myocardial infarction. Angiographic microvascular obstruction incidence tended to be less in ELCA-treated patients compared with DPD-treated patients (3 [13%] vs 15 [32%], p = 0.09). Type IVa myocardial infarction incidence was more in DPD-treated patients compared with ELCA-treated patients (23 [49%] vs 5 [21%], p = 0.04). In conclusion, in patients with non-ST elevation acute coronary syndrome undergoing PCI of degenerated SVG, ELCA compared with DPD, is associated with a trend for better myocardial reperfusion and a lesser incidence of periprocedural necrosis. Controlled randomized trials are warranted to confirm these early observations.
The American journal of cardiology 08/2013; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:To evaluate the long-term effects of drospirenone (DRSP)/ethinylestradiol (EE) alone, metformin alone, and DRSP/EE-metformin on CD4(+)CD28(null) T lymphocytes frequency, a cardiovascular risk marker, in patients with hyperinsulinemic polycystic ovary syndrome (PCOS).Design:Randomized clinical trial.Interventions:Ninety three patients with hyperinsulinemic PCOS were age matched and body mass index matched and randomized to receive a 6 months daily treatment with DRSP (3 mg)/EE (0.03 mg), or metformin (1500 mg), or DRSP/EE combined with metformin.Main Outcome Measures:CD4(+)CD28(null) T-cell frequencies.Results:The DRSP/EE and metformin groups did not show any significant change in the CD4(+)CD28(null) frequency compared to the baseline. Interestingly, a statistically significant decrease in CD4(+)CD28(null) frequency occurred after 6 months of DRSP/EE-metformin (median 3-1.5; P < .01). Of note, this statistically significant association was confirmed after adjusting for baseline values in DRSP/EE-metformin group by analysis of covariance (P < .05).Conclusions:In women with hyperinsulinemic PCOS, combined therapy with DRSP/EE and metformin may reduce cardiovascular risk.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: This study sought to assess whether intracoronary adenosine or nitroprusside following thrombus aspiration (TA) is superior to TA alone for the prevention of microvascular obstruction (MVO) in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: MVO, due to its multifactorial pathogenesis, still occurs after TA in a sizeable portion of patients. METHODS: We performed a placebo-controlled, randomized, open-label, blind-examination, multicenter trial. A total of 240 STEMI patients with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0/1 were randomly allocated 1:1:1 to receive adenosine (n = 80), nitroprusside (n = 80), or saline (n = 80) given distal to the occluded site after TA. The primary endpoint was the incidence of ST-segment resolution (STR) >70% on surface electrocardiogram at 90 min after PCI. Secondary endpoints were angiographic MVO incidence (TIMI flow grade ≤2 or 3 with a myocardial blush grade <2) and major adverse cardiac event (MACE) rate at 30 days as a composite of cardiac death, myocardial infarction, target lesion revascularization, and heart failure requiring hospitalization. RESULTS: STR >70% occurred in in 71% of adenosine-treated patients, in 54% of nitroprusside-treated patients, and in 51% of saline-treated patients (p = 0.009 and p = 0.75, respectively, vs. saline). Angiographic MVO occurred in 18% of adenosine-treated patients, in 24% of nitroprusside-treated patients, and in 30% of saline-treated patients (p = 0.06 and p = 0.37, respectively, vs. saline). MACE occurred in 10%, 14%, and 20% of patients, respectively (p = 0.08 and p = 0.29 vs. saline). CONCLUSIONS: In STEMI patients treated by PCI and TA, the additional intracoronary administration of adenosine, but not that of nitroprusside, results in a significant improvement of MVO, as assessed by STR.
[Show abstract][Hide abstract] ABSTRACT: The primary goal in reopening an infarct-related artery is the restoration of myocardial tissue-level perfusion. In a variable proportion of patients with ST-elevation myocardial infarction, however, microcirculatory impairment may persist after epicardial coronary artery recanalization. This phenomenon is known as microvascular obstruction (MVO). Ischemic injury, reperfusion injury, and distal embolization along with the individual response to each of these mechanisms are variably involved in the pathogenesis of MVO in the single patient. Importantly, MVO is associated with a worse prognosis both at short- and long-term follow-up. MVO can be assessed in the cath-lab by simple angiographic indexes, such as Thrombolysis in Myocardial Infarction grade score and Myocardial Blush Grade, or by invasive measures of coronary flow pattern. Imaging techniques, such as myocardial contrast echocardiography or cardiac magnetic resonance, and ST-segment resolution on standard electrocardiogram are used in the days following reperfusion with the patient in the coronary care unit. In this article, we review the available data regarding pathogenesis, diagnosis and the prognostic significance of MVO after primary percurtaneous coronary intervention in ST-elevation myocardial infarction patients, with a brief highlighting on the crucial role of its prevention and its early detection.
Current Vascular Pharmacology 03/2013; 11(2):245-262. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The primary goal in patients with ST-elevation myocardial infarction (STEMI) is the restoration of myocardial tissue-level perfusion. In a variable proportion of patients with STEMI, however, microcirculatory impairment may persist after epicardial coronary artery recanalization. This phenomenon is known as "myocardial no-reflow". Of note, no-reflow is associated with a worse prognosis both at short- and long-term follow-up. Depending on the population under study and the diagnostic technique used for its detection, the incidence of no-reflow ranges from 5 to 50%. No-reflow can be directly assessed in the cath-lab in several ways, including angiographic Thrombolysis in Myocardial Infarction (TIMI) flow grade assessment and more complex angiographic indexes, such as TIMI frame count, TIMI perfusion grade, myocardial blush grade, or by direct invasive assessment of coronary flow. After the cath-lab, both the evaluation of electrocardiographic ST-segment resolution and imaging techniques, as myocardial contrast echocardiography or cardiac magnetic resonance, are able to monitor no-reflow evolution, with imaging playing a crucial role in its quantification. In this article, we review indexes of no-reflow used both in the cath-lab and thereafter.
Current pharmaceutical design 12/2012; · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsWe aimed to compare coronary artery disease (CAD) at the time of a first acute coronary syndrome (ACS) in type II diabetic and non-diabetic patients by coronary angiography and by optical coherence tomography (OCT).Methods and resultsTwo different patient populations with a first ACS were enrolled for the angiographic (167 patients) and the OCT (72 patients) substudy. Angiographic CAD severity was assessed by Bogaty, Gensini, and Sullivan scores, whereas collateral development towards the culprit vessel was assessed by the Rentrop score. Optical coherence tomography plaque features were evaluated at the site of the minimum lumen area (MLA) and of culprit segment. In the angiographic substudy, at multivariate analysis, diabetes was associated with both the stenosis score and the extent index (P = 0.001). Furthermore, well-developed collateral circulation (Rentrop 2-3) towards the culprit vessel was more frequent in diabetic than in non-diabetic patients (73% vs. 16%, P = 0.001). In the OCT substudy, at MLA site lipid quadrants were less and the lipid arc was smaller in diabetic than in non-diabetic patients (2.3 ± 1.3 vs. 3.0 ± 1.2; P = 0.03 and 198° ± 121° vs. 260° ± 118°; P = 0.03). Furthermore, the most calcified cross-section along the culprit segment had a greater number of calcified quadrants and a wider calcified arc in diabetic than in non-diabetic patients (1.7 ± 1.0 vs. 1.2 ± 0.9; P = 0.03 and 126° ± 95° vs. 81° ± 80°; P = 0.03). Superficial calcified nodules were more frequently found in diabetic than in non-diabetic patients (79 vs. 54%, P = 0.04).Conclusions
In spite of potent pro-inflammatory, pro-oxidant and pro-thrombotic stimuli operating in type II diabetes, diabetic patients exhibit substantially more severe coronary atherosclerosis than non-diabetic patients at the time of a first acute coronary event. Better collateral development towards the culprit vessel, a predominantly calcific plaque phenotype and, probably, yet unknown protective factors operating in diabetic patients may explain these intriguing paradoxical findings.
European Heart Journal 11/2012; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Progression of coronary atherosclerosis (ATS) has clinical implications. Serum levels of γ-glutamyltransferase (GGT), a marker of oxidative stress, predict the risk of cardiovascular events. However, the role of GGT levels in the progression of coronary ATS has never been established. MATERIALS AND METHODS: Consecutive patients undergoing two coronary angiographies (CAs) separated by at least 6 months were prospectively enrolled between May 2008 and June 2010. All patients were discharged on statins after the first CA. The severity and extent of coronary ATS were graded according to Bogaty's score, and the variation ([INCREMENT]) in stenosis score and extent index between follow-up (S2 and E2) and basal values (S1 and E1) were calculated. Predictors of [INCREMENT]S2-1 and [INCREMENT]E2-1 were assessed among clinical and laboratory data, including GGT levels, analyzed as [INCREMENT] between follow-up and basal values ([INCREMENT]GGT2-1). RESULTS: We enrolled 100 consecutive patients (age 64±11 years, 68% men). Compliance with statin therapy was 100%. At multiple regression analysis, [INCREMENT]GGT2-1 was the only independent predictor of [INCREMENT]S2-1 (B=0.18, SE=0.07, P=0.05), with [INCREMENT]low-density lipoprotein-cholesterol2-1 levels being of borderline statistical significance (P=0.07). On multiple regression analysis, [INCREMENT]GGT2-1 was the only independent predictor of [INCREMENT]E2-1 (B=0.32; SE=0.11; P=0.04), with active smoking habit and [INCREMENT]fibrinogen2-1 levels being of borderline statistical significance (P=0.08 and 0.06, respectively). CONCLUSION: [INCREMENT]GGT2-1 is associated with angiographic coronary ATS progression in patients with ischemic heart disease on statin treatment, suggesting that oxidative stress may be another therapeutic target for preventing ATS progression beyond that of lipid-lowering therapies.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To study the frequency of CD4(+)CD28(null) T cells, which are aggressive T lymphocytes associated with recurrent coronary instability and type 2 diabetes mellitus, in different polycystic ovary syndrome (PCOS) phenotypes and in age- and body mass index-matched healthy women. DESIGN: Retrospective cohort observational study. SETTING: Unit of human reproductive pathophysiology, university hospital. PATIENT(S): A total of 167 PCOS patients and 102 control subjects. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CD4(+)CD28(null) T cell frequency, high-sensitive C-reactive protein levels, and other glucose-metabolic parameters. RESULT(S): CD4(+)CD28(null) frequency was significantly higher in all PCOS groups than in control subjects. CD4(+)CD28(null) frequency was significantly higher in nonhyperandrogenic phenotype (5.7%, range 3.2-7.1) than in phenotypes with hyperandrogenism (H) + oligoamenorrhea (O) + polycystic ovary (PCO) (3.5%, range 1-5.8), H + O (3%, range 1.8-4.7), and H + PCO (2.63%, range 1.2-4.1). The relative risk of non-H phenotype for PCOS women in the highest quartile for CD4(+)CD28(null) frequency compared with PCOS women with the lowest quartile was 3.2 (95% confidence interval 1.9-5.8). CONCLUSION(S): Cardiovascular risk evaluation should be performed in all PCOS phenotypes. In particular, we demonstrated that the non-H phenotype has potentially increased cardiovascular risk in terms of CD4(+)CD28(null) frequency.
Fertility and sterility 09/2012; · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary aneurysmatic dilatation may be localized to a segment or may involve multiple segments. We herein report a case of a diffuse aneurysmatic dilatation of the right coronary artery.
Journal of Cardiovascular Medicine 08/2012; · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The success rate of recanalization of coronary chronic total occlusion (CTO) has improved in recent years, but the clinical benefit associated with successful CTO recanalization in the drug-eluting stent (DES) era is not well known. A cohort of 317 consecutive patients (mean age 65 ± 10, 84% men) with CTOs (defined as Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 and duration >3 months) of native coronary vessels in which percutaneous coronary intervention was attempted was enrolled from June 2005 to March 2009. All successful procedures (196 patients) were performed by DES implantation. The incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and repeat revascularization) was assessed during a mean follow-up period of 3 years. MACE predictors were assessed in clinical, angiographic, and procedural data, including procedural success. Patients with successful percutaneous coronary intervention experienced a significantly lower MACE rate compared to those with failed procedures (17 [9%] vs 32 [26%], p = 0.008). Patients with multivessel disease experienced MACEs more frequently than those with single-vessel disease (45 [22%] vs 4 [4%], p = 0.002). On multiple Cox regression analysis, the presence of multivessel disease and CTO opening failure were independent predictors of MACEs (hazard ratio 2.31, 95% confidence interval 1.17 to 4.96, p = 0.01, and hazard ratio 1.81, 95% confidence interval 1.33 to 4.12, p = 0.02, respectively). The worst prognosis was confined to patients with multivessel disease and failed procedures (hazard ratio 2.73, 95% confidence interval 1.21 to 3.92, p = 0.03). In conclusion, successful recanalization of CTOs with DES translates into a reduction of the 3-year MACE rate compared to failed procedures, and the worst prognosis is observed in patients with failed procedures and multivessel disease, a notion that might be taken into account in the management of patients with coronary CTOs.
The American journal of cardiology 06/2012; 110(7):948-53. · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Low density lipoproteins (LDL) with an electronegative charge [LDL(-)] may cause endothelial injury. We assessed the association between serum LDL(-) levels and coronary artery disease (CAD) severity.
We prospectively enrolled patients with CAD angiographic evidence [stable angina (SA) or non-ST-elevation-acute coronary syndrome (NSTE-ACS)], or with normal coronary arteries (NCA). Baseline LDL(-) serum levels were measured in all patients. Angiographic CAD extent was assessed by using the Bogaty extent index, while CAD severity by evaluating the presence of multi-vessel disease.
Forty-seven patients (age 61 ± 9 years, male sex 60%) were enrolled (17 SA, 15 NSTE-ACS and 15 NCA patients). LDL(-) levels were significantly higher in SA [21% (18-34) p = 0.0001] and NSTE-ACS [22% (18-28), p = 0.0001] as compared to NCA [6% (5-8)], without significant differences between SA and NSTE-ACS (p = 0.92). Multi-vessel disease patients had higher LDL(-) levels as compared to single-vessel disease patients (p = 0.002) but similar total LDL levels (p = 0.66). LDL(-) significantly correlated with extent index (r = 0.38, p = 0.03), while total LDL did not (p = 0.24).
LDL(-) serum levels are associated with CAD angiographic severity and extent. This exploratory analysis should prime further larger studies in order to assess LDL(-) proatherogenic role.