Rosuvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of myocardial periprocedural necrosis: the ROMA trial.

OBJECTIVES: The aim of this study is to assess the efficacy of the high-dose rosuvastatin preadministration in reducing periprocedural myocardial necrosis and major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing elective percutaneous coronary intervention (PCI). BACKGROUND: Elective PCI may be complicated with an elevation of cardiac biomarkers. Several studies suggested that pretreatment with statins may be associated with a reduction in periprocedural myocardial necrosis. METHODS: One hundred and sixty patients with stable angina who underwent elective PCI were randomly assigned to receive either a preprocedural loading dose (40 mg) of rosuvastatin group (RG, n = 80) or a standard treatment [control group (CG), n = 80].The primary endpoint was the incidence of periprocedural myocardial necrosis. The secondary endpoint was the assessment of MACCE [cardiac death, all-myocardial infarction (MI), stroke, and target vessel revascularization (TVR)] at a 30-day and 12-month follow-up, as well as the rate of periprocedural rise of Troponin T-serum levels >3× upper limit of normal. RESULTS: Twelve and 24-hr post-PCI creatinine kinase MB isoform elevation >3× occurred more frequently in the CG than in the RG (22.7 vs. 7.1; P = 0.034 and 26.4 vs. 8.7; P = 0.003). At the 30-day and 12-month follow-up, the incidence of cumulative MACCE was higher in CG than in the RG (30.0% vs. 8.7%; P = 0.001 and 35.0% vs. 12.5%; P = 0.001).The difference between the groups was mainly due to the periprocedural MI incidence (26.4% vs. 8.7%; P = 0.003).The rate of cardiac death, spontaneous MI, TVR, and stroke were similar in the two groups. CONCLUSIONS: High loading dose of rosuvastatin within 24 hr before elective PCI seems to decrease the incidence of periprocedural myocardial necrosis during a period of 12-months compared to the standard treatment.

The effect of thrombectomy on myocardial blush in primary angioplasty: the Randomized Evaluation of Thrombus Aspiration by two thrombectomy devices in acute Myocardial Infarction (RETAMI) trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) may cause thrombus dislodgment leading to microvascular function impairment, which is a negative independent predictor of myocardial function recovery. Compared with conventional stenting, pretreatment with aspiration thrombectomy during primary PCI significantly improves coronary epicardial flow and myocardial tissue perfusion parameters. We sought to evaluate the angiographic findings of two different manual aspiration thrombectomy devices (Diver-Invatec (DI) and Export-Medtronic (EM)) in STEMI patients undergoing primary angioplasty. METHODS: We randomized 103 STEMI patients referred to our hospital to undergo primary PCI (<12 hr from symptoms onset) to DI (n = 52) and EM (n = 51) devices. The primary angiographic composite end-points were the rates of post-thrombectomy thrombus score (TS) < or =2, TIMI flow grade > or =2, and post-stenting myocardial blush grade (MBG) > or =2 in the two groups. RESULTS: Baseline, clinical, and angiographic preprocedural findings did not differ between the two groups. After aspiration thrombectomy, a TS < or = 2 was more frequently present in EM group (92.3 vs. 69.3%, P = 0.0052). Also the rate of post-thrombectomy TIMI > or = 2 (69.3 vs. 92.2%, P = 0.0052) and post-stenting MBG > or =2 (88.2 vs. 69.3%, P = 0.029) were significantly higher in EM group. No significative differences were observed in terms of clinical events at 1 and 12 months. CONCLUSIONS: In this single-center, prospective, randomized study, a EM use before stenting in STEMI patients seems to remove more thrombotic burden compared with DI, providing a greater post-thrombectomy epicardial flow and a better post-stenting microvascular perfusion.

Comparison between sirolimus- and paclitaxel-eluting stent in T-cell subsets redistribution.

We sought to investigate the effects of 2 different coronary drug-eluting stents on the distribution of central or effector memory T cells circulating in the coronary sinus of patients with coronary artery disease who underwent percutaneous coronary revascularization. We randomly assigned 43 patients (mean age 65.4 +/- 4.3 years; 34 men) presenting with stable coronary disease and angiographically proved stenosis of the left anterior descending artery to treatment with sirolimus- or paclitaxel-eluting stents. Heparinized blood samples were obtained from the coronary sinus before and 20 minutes after stent implantation. Analysis of surface phenotype was performed by 4-color flow cytometry, and data are expressed as the percentage of positive cells. The percentages of CD8+ and CD4+ effector memory T cells, as defined by the CD3+CD45RO+CD27- phenotype, were significantly reduced in patients who received a sirolimus-eluting stent compared with the basal values. Conversely, the percentages of CD8+, but not CD4+, central memory T cells (CD3+CD45RO+CD27+) were increased in the same treatment group after the revascularization procedure. No changes in the percentages of memory T-cell populations in the paclitaxel-eluting stent group were observed. These findings show that sirolimus-eluting stents rapidly induced a redistribution of memory T lymphocytes, with a significant decrease of proinflammatory effector memory T cells circulating within the coronary sinus.

Levosimendan improves hemodynamics and coronary flow reserve after percutaneous coronary intervention in patients with acute myocardial infarction and left ventricular dysfunction.

BACKGROUND: Positive inotropic agents may be associated with increasing myocardial ischemia or malignant arrhythmias. Levosimendan, a new calcium sensitizer, with its little effect on myocardial oxygen demand is better tolerated by patients with acute coronary syndromes. We evaluated the acute effects of levosimendan on hemodynamics and coronary flow velocities in patients with left ventricular (LV) dysfunction undergoing percutaneous coronary interventions (PCIs) for an acute myocardial infarction (AMI). METHODS: Patients with AMI and LV dysfunction undergoing primary PCI were randomized to intravenous infusion of levosimendan (10 minutes bolus with 12 microg/kg followed by 0.1 microg/kg per minute for 24 hours) or placebo, 10 minutes after a primary PCI. Evaluation of hemodynamics and of coronary flow reserve (CFR) were performed at baseline and after bolus. RESULTS: Twenty-six consecutive patients (mean age 57 +/- 5.4 years, 18 males) were included into the study. At baseline, mean values of hemodynamics and coronary flow velocities were comparable between groups. After bolus, patients with levosimendan (n = 12) showed a significant decrease of pulmonary capillary wedge pressure (from 24 to 19 mm Hg) and a significant increase of cardiac index (from 1.8 to 2.4 L/m2 per minute) resulting in a significant decrease of systemic vascular resistance (from 1366 to 1075 [dyne . s]/cm2). Moreover, CFR on infarct-related artery and on reference vessel significantly improved in patients treated with levosimendan (from 1.6 to 2.0 and from 2.1 to 2.4, respectively). On the other hand, no statistically significant changes have been observed in the placebo group (n = 14). CONCLUSIONS: Levosimendan, given intravenously after a PCI procedure in patients with AMI and LV dysfunction, significantly improves hemodynamics and CFR, compared with placebo.

Altered trafficking of CD8+ memory T cells after implantation of rapamycin-eluting stents in patients with coronary artery disease.

Aim of this study was to investigate the effects of implantation of different coronary drug-eluting stents on trafficking of central (T(CM)) or effector (T(EM)) memory T cells in the coronary sinus of patients with coronary artery disease (CAD) undergoing percutaneous coronary revascularization. Thirty-two patients presenting with stable coronary disease and angiographically proven stenosis of left descending coronary artery were randomly assigned to treatment with rapamycin-eluting, paclitaxel-eluting or bare metal stents. Heparinized blood samples were obtained from the coronary sinus either before or 20 min after stent implantation. Mononuclear cells were stained with mAbs specific for CD3, CD4, CD8, CD45R0, and CD27 molecules. Analysis of surface phenotype was performed by four-color flow cytometry and data on both CD4+ and CD8+ T(CM) and T(EM) cells were expressed either as absolute cell numbers/microL of blood or as percentages relative to the corresponding total memory T cell populations in the individual patients. We found that the number of CD8+ T(EM), as defined by CD3+CD45R0+CD8+CD27- phenotype, was significantly reduced in patients receiving a rapamycin-eluting stent as compared with basal values. Conversely, the number of CD8+ T(CM) (CD3+CD45R0+CD8+CD27+) was increased in the same treatment group after the revascularization procedure. No changes in the absolute number of CD4+ and CD8+ total (T(CM) plus T(EM)) memory T cells before and after the procedure were observed. These findings suggest that rapamycin eluted from medicated coronary stents rapidly induce a redistribution of memory CD8+ T lymphocyte subsets, with a significant decrease of T(EM) and a corresponding increase of T(CM) increase circulating within the coronary sinus. This anti-inflammatory effect could partially explain the reduction of coronary in-stent restenosis rate associated with the clinical use of this type of device.

Pharmacodynamic effect of switching therapy in patients with high on-treatment platelet reactivity and genotype variation with high clopidogrel Dose versus prasugrel: the RESET GENE trial.

BACKGROUND: High on-treatment platelet reactivity (HTPR) is associated with adverse outcomes. We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs. METHODS AND RESULTS: Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay, defining HTPR as area under the curve >450. Those with HTPR were randomized to prasugrel (10 mg/day) or high-dose clopidogrel (150 mg/day) for 2 weeks and then crossed-over to, respectively, clopidogrel and prasugrel, repeating the P2Y12 assay at the end of each cycle. Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients. The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel. Thirty-two patients were randomized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel. Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was (325.8 versus 478.5 area under the curve, P=0.028). No patient treated with prasugrel exhibited HTPR, whereas 9 (28.1%) receiving high-dose clopidogrel still had prevalence of HTPR (P=0.001). Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable. Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274), whereas it was significantly worse in the 14 (43.7%) carriers (HTPR in 43.7% versus 0, P=0.003). CONCLUSIONS: HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype. Conversely, high-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01465828.

Incidence of contrast-induced acute kidney injury associated with diagnostic or interventional coronary angiography.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) represents an important cause of hospital-acquired AKI. The aim of this study was to evaluate the incidence of CI-AKI after coronary angiography (CA) or percutaneous coronary intervention (PCI) and the role of patient-/procedure-related risk factors. METHODS: For 11 months, patients undergoing CA or PCI were prospectively evaluated for CI-AKI, and factors possibly affecting CI-AKI were analyzed. Statistical analysis was completed using Student's t-test, chi-square or Fisher exact test, and multivariate logistic regression. RESULTS: Among 585 consecutive patients, incidence of CI-AKI was 5.1% (n=30) and renal replacement therapy was required in 10% of those (n=3). Incidence of CI-AKI was higher in patients with anemia or chronic kidney disease (CKD) associated with diabetes. Basal hemoglobin was significantly lower in CI-AKI patients while Mehran score, contrast medium (CM) volume, contrast ratio (CM volume / maximum contrast dose) and ratio glomerular filtration rate (CM volume / GFR) were significantly higher. Multivariate analysis selected a higher contrast ratio as a factor independently associated with a higher risk of CI-AKI which otherwise appeared to be lower with increasing basal hemoglobin. CONCLUSIONS: The incidence of CI-AKI after CA or PCI was higher in patients with CKD associated with diabetes. Lower levels of basal hemoglobin appeared to be related to a higher risk of CI-AKI, and contrast media volume, especially if exceeding the dose adjusted for renal function, was a strong modifiable risk factor for CI-AKI.

Impact of thrombectomy with EXPort Catheter in Infarct-Related Artery during Primary Percutaneous Coronary Intervention (EXPIRA Trial) on cardiac death.

In ST-segment elevation myocardial infarction (STEMI) impairment of microcirculatory function is a negative independent predictor of myocardial function recovery. In the Impact of Thrombectomy with EXPort Catheter in Infarct-Related Artery during Primary Percutaneous Coronary Intervention (PCI; EXPIRA) trial we found that manual thrombectomy resulted in a better myocardial reperfusion expressed by an improved procedural outcome and a decrease of infarct size compared to conventional PCI. The aim of the present study was to investigate whether the early efficacy of thrombus aspiration translates into very long-term clinical benefit. We randomized 175 patients with STEMI with occlusive thrombus at baseline undergoing primary PCI to thromboaspiration with a manual device (Export Medtronic, n = 88) or standard PCI (n = 87). No differences in baseline, clinical, and angiographic preprocedural findings were observed between the 2 groups except for incidence of hypertension and cholesterol levels. After 24 months major adverse cardiac events were 13.7% versus 4.5% (p = 0.038, log-rank test) and cardiac death was 6.8% versus 0% (p = 0.012, log-rank test). A strict correlation was observed between cardiac death incidence and tissue reperfusion parameters (postprocedural myocardial blush grade and ST-segment resolution). In conclusion, manual thrombus aspiration before stenting of the infarct-related artery in selected patients with STEMI improving myocardial reperfusion significantly decrease cardiac death and major adverse cardiac events at 2 years.

A multicenter randomized study to evaluate intracoronary abciximab with the ClearWay catheter to improve outcomes with Lysis (IC ClearLy): trial study design and rationale.

BACKGROUND: Percutaneous coronary intervention (PCI) is a highly effective therapy for acute ST-elevation myocardial infarction. Adjunctive therapy with platelet glycoprotein (GP) IIb/IIIa inhibitor can result in increased vessel patency and improved outcomes in ST-elevation myocardial infarction patients undergoing PCI. The investigation of novel dosing and delivery strategies of this therapy may help to further improve outcomes. METHODS: IC-Clearly is a randomized, open-label, multicenter trial, with the purpose of evaluating the effectiveness of an intracoronary bolus dose of abciximab delivered using the ClearWay RX catheter vs. an intravenous bolus of abciximab for ST-elevation myocardial infarction with angiographically visible thrombus (thrombus grade >or=2). A total of 150 patients will be randomized 1: 1 to treatment of the culprit artery with intracoronary abciximab (75 patients) or intravenous abciximab (75 patients) in addition to a maintenance infusion regimen of abciximab administered intravenously for 12 h after PCI. The number of patients included in this study is based on the estimation of sample size needed to identify a statistically significant difference in the primary endpoints between the two groups. The primary endpoint chosen to evaluate this hypothesis is infarct size assessed by cardiac magnetic resonance. Clinical outcomes will be assessed for each patient through hospital discharge and at 30-day follow-up. CONCLUSION: The purpose of this study is to evaluate whether an intracoronary bolus of abciximab delivered with the ClearWay RX catheter prior to the 12 h post-PCI intravenous infusion regimen of abciximab will result in significant additional clot resolution in vivo and improved myocardial perfusion when compared with an intravenous bolus of abciximab on top of the 12 h post-PCI intravenous infusion regimen of abciximab as per standard practice. The primary endpoint chosen to evaluate this hypothesis is infarct size as assessed by cardiac magnetic resonance.

[Secondary cardiovascular prevention after acute coronary syndrome in clinical practice]. / Prevenzione cardiovascolare secondaria dopo sindrome coronarica acuta nella pratica clinica.

Secondary prevention after acute coronary syndromes should be aimed at reducing the risk of further adverse cardiovascular events, thereby improving quality of life, and lengthening survival. Despite compelling evidence from large randomized controlled trials, secondary prevention is not fully implemented in most cases after hospitalization for acute coronary syndrome. The Lazio Region (Italy) has about 5.3 million inhabitants (9% of the entire Italian population). Every year about 11 000 patients are admitted for acute coronary syndrome in hospitals of the Lazio Region. Most of these patients receive state-of-the art acute medical and interventional care during hospitalization. However, observational data suggest that after discharge acute coronary syndrome patients are neither properly followed nor receive all evidence-based treatments. This consensus document has been developed by 11 Scientific Societies of Cardiovascular and Internal Medicine in order develop a sustainable and effective clinical approach for secondary cardiovascular prevention after acute coronary syndrome in the local scenario of the Lazio Region. An evidence-based simplified decalogue for secondary cardiovascular prevention is proposed as the cornerstone of clinical intervention, taking into account regional laws and relative shortage of resources. The following appropriate interventions should be consistently applied: smoking cessation, blood pressure control (blood pressure < 130/80 mmHg), optimal lipid management (LDL cholesterol < 80 mmHg), weight and diabetes management, promotion of physical activity and rehabilitation, correct use of antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers.

Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary intervention) prospective, randomized trial.

OBJECTIVES: The purpose of this study was to evaluate the impact on myocardial perfusion and infarct size as assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of a manual thrombectomy device, Export Medtronic (EM) (Medtronic Inc., Minneapolis, Minnesota), as adjunctive therapy in primary percutaneous coronary intervention (PPCI) in a subset of patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND: PPCI may cause thrombus dislodgment, leading to microvascular damage. METHODS: One hundred seventy-five STEMI patients were randomly assigned to standard percutaneous coronary intervention (PCI) (n = 87) or EM-PCI (n = 88). The primary end points were the occurrence of myocardial blush grade > or =2 and the rate of 90-min ST-segment resolution >70%. The CE-MRI substudy was performed in 75 patients with anterior STEMI to assess microvascular obstruction and infarct size. RESULTS: Myocardial blush grade > or =2 and ST-segment resolution occurred more frequently in the EM-PCI group (88% vs. 60%, p = 0.001; and 64% vs. 39%, p = 0.001). In the acute phase, microvascular obstruction extent was significantly lower in the EM-PCI group and at 3 months, infarct size was significantly reduced only in the EM-PCI group. A lower incidence of cardiac death in the EM-PCI group (4.6% vs. 0%, log-rank test p = 0.02) was observed at 9 months. CONCLUSIONS: Thrombectomy prevents thrombus embolization and preserves microvascular integrity reducing infarct size, and it therefore represents an useful adjunctive therapy in PPCI.

Comparison between balloon angioplasty and additional coronary stent implantation for the treatment of drug-eluting stent restenosis: 18-month clinical outcomes.

OBJECTIVE: To evaluate the long-term outcomes after different modalities of treatment of drug-eluting stent (DES) in-stent restenosis (ISR) in a 'real world' setting. METHODS: Actually, few and conflicting data are available about the management of in-stent restenosis (ISR) after DES implantation. In our 'real world' registry 1082 consecutive patients who received a DES implantation were included. At 9-month angiographic follow-up, 93 patients presented a DES ISR that was treated with 'homo-DES' (HMD) (N = 27), 'hetero-DES' (HTD) (N = 19) and conventional balloon angioplasty (POBA) (N = 47). We evaluated the clinical outcomes in terms of major adverse cardiac event (MACE) (death, myocardial infarction and target vessel revascularization) at 18 months. RESULTS: There was no difference for clinical and angiographic characteristics between the three groups, except for the presence of silent ischaemia as clinical presentation (7.7 HMD vs. 2.2% POBA; P = 0.0001). No late stent thrombosis was found. At 18-month clinical follow-up patients treated with HMD, HTD and POBA presented a rate of MACE of 10.2, 0 and 8.7%, respectively (P = NS). Kaplan-Meier survival probability showed that HTD and POBA treatment tended to have more favourable outcomes at 18 months than the HMD treatment. CONCLUSION: In our registry, POBA seems to be as effective as other DES implantations in cases of DES ISR, especially in cases of focal type (Mehran classification IA, IC), in terms of long-term outcomes.

[Thrombectomy in primary angioplasty]. / La trombectomia nell'angioplastica primaria.

Primary percutaneous coronary intervention is the standard treatment in patients with ST-segment elevation myocardial infarction achieving a TIMI 3 flow in more than 90% of patients. However, despite a brisk epicardial coronary flow in the infarct-related artery, frequently post-ischemic microvascular damage limits the efficacy of primary PCI. Recent studies suggest that thrombectomy during primary PCI, in patients with intracoronary angiographically visible thrombus, represents a useful adjunct to pharmacotherapy able to prevent distal embolization.

Rotational atherectomy in the distal left anterior descending coronary artery through an internal mammary artery graft.

We report the case of a 53-year-old white man who began complaining of dyspnoea and angina 19 months after coronary artery bypass graft surgery. Coronary angiography revealed the presence of a long and critical stenosis in the native left anterior descending coronary artery, shortly after distal anastomosis of the left internal mammary artery. After failed predilatations with standard or cutting balloons, we successfully used the rotablator system, which allowed us to implant a bare-metal stent in the native left anterior descending coronary artery. However, stent deployment caused long linear graft dissection, which was reduced by drug-eluting stent implantation in the proximal and distal segments of the left internal mammary artery.

Effects of levosimendan on left ventricular diastolic function after primary angioplasty for acute anterior myocardial infarction: a Doppler echocardiographic study.

BACKGROUND: Levosimendan is a new Ca-sensitizing drug with combined positive inotropic and vasodilatory effects that offers new therapeutic possibilities in patients with severe heart failure. Compared with other inotropic agents, animal studies demonstrated that levosimendan does not impair left ventricular diastolic function. OBJECTIVE: We sought to evaluate the effects of levosimendan on left ventricular diastolic function, using conventional transmitral Doppler and Doppler tissue imaging parameters, in patients with anterior acute myocardial infarction undergoing primary angioplasty. METHODS: After a successful primary angioplasty, we randomized 52 consecutive patients with anterior acute myocardial infarction to levosimendan or placebo infusion and analyzed the diastolic function using conventional transmitral Doppler flow and Doppler tissue imaging at mitral annulus. RESULTS: At 24 hours after the index intervention, patients treated with levosimendan (n = 26) showed a significant reduction of the isovolumetric relaxation time (114.6 +/- 15.1-69.2 +/- 5.6 milliseconds; P = .001) and the ratio between the early diastolic flow and early tissue velocity (E/E') (21.4 +/- 10.7-12.8 +/- 7.3; P = .04), and a significant increase of the ratio between the early and late diastolic flow (E/A) (0.86 +/- 0.33-1.52 +/- 0.88; P = .03) and E' (6.4-7.9 cm/s; P = .001). On the other hand, only a significant increase in E/A ratio (0.97 +/- 0.32-1.64 +/- 0.51; P = .002) was observed in the placebo group (n = 26). CONCLUSIONS: Levosimendan, after primary angioplasty in patients with anterior acute myocardial infarction, appears to improve the Doppler echocardiographic parameters of left ventricular diastolic function.