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Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e-33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e-09, 4.53e-08, and 2.60e-10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aims: Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial., Methods and Results: We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10-54; CES1 G143E, P = 1.3 × 10-16; CYP2C19*17, P = 9.5 × 10-10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10-4; CYP2B6 516 G > T, P = 1.0 × 10-3; CYP2C9*2, P = 1.2 × 10-3; and CYP2C9*3, P = 1.5 × 10-3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14-2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35-14.27, P = 0.01) compared to patients who carried six or fewer of these alleles., Conclusion: Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Fractional flow reserve (FFR) is considered the gold standard for functional assessment of coronary stenosis in stable coronary artery disease. The use of FFR enables an ischemia-guided revascularization with improvement of clinical outcomes in a cost-effective fashion. Both clinical and interventional cardiologists should be aware of the advantages and potential pitfalls of this technique. We focus on FFR with the aim to provide the clinical cardiologist with information on indications and technical aspects to confirm a correct execution of FFR in different coronary anatomical settings.

Introduction: Thrombin generation (TG) is a central step of the coagulation system involved in hemostatic and thrombotic roles. Scarce data evaluating in the acute phase the association between TG and the risk of cardiovascular death of acute coronary syndrome (ACS) patients are available, in the era of percutaneous coronary intervention (PCI) and stenting with the use of dual antiplatelet treatment., Materials and Methods: We investigated TG in 292 ACS patients undergoing PCI with stent implantation on dual antiplatelet treatment. Venous samples were obtained 12-24h after PCI. TG was assessed using the Calibrated Automated Thrombogram (CAT)., Results: At two years of follow-up, 57 out of 292 patients (19.5%) died from cardiovascular causes. Higher values of endogenous thrombin potential (ETP) [1115.9 (705-1441.3) vs 940.2 (666.0-1253.1), p=0.049], peak [176.1 (80.5-259.4) vs 107.3 (59.9-181.1), p=0.002] and velocity index [61.75 (21.03-97.88) vs 25.64 (11.95-50.90), p<0.001] were observed in relation to survival patients. At the multivariate model adjusted for the Global Registry of Acute Coronary Events risk score, the association between TG and cardiovascular death remained significant for ETP [OR (95% CI): 2.58 (1.10-6.03), p=0.029], peak [OR (95%CI): 3.27 (1.35-7.92), p=0.009] and velocity index [OR (95% CI): 3.06 (1.27-7.39), p=0.013]. This result was confirmed after adjustment for high on-treatment platelet reactivity [ETP: OR (95% CI) 2.35 (1.11-5.00), p=0.027; peak: OR (95% CI) 2.42 (1.13-5.15), p=0.022; velocity index: OR (95% CI) 2.43 (1.14-5.20), p=0.022]., Conclusions: ACS patients with a residual TG after PCI and stent implantation have a significantly higher risk of long-term cardiovascular death. These results might be useful in improving risk stratification for ACS patients and support the need of a tailored antithrombotic therapy., (Copyright © 2016. Published by Elsevier Ltd.)

Aims: To compare the effects of two thrombus aspiration devices, the manual catheter Export® and the more complex and expensive mechanical Angiojet®, on several indices of reperfusion in acute ST-elevation myocardial infarction (STEMI)., Methods and Results: Clinical, hemodynamic and procedural characteristics of 185 STEMI patients, randomized to treatment with Export (n=95) or Angiojet (n=90) during primary percutaneous coronary intervention (PPCI) were analyzed. The primary endpoint was ST-segment elevation reduction 90 min after culprit vessel re-opening. Secondary endpoints included variations in some angiographic parameters (TIMI Flow, TIMI Frame Count and Myocardial Blush Grade) and Infarct Size and Severity at myocardial scintigraphy. A significant reduction in ST-elevation was observed in both groups after PPCI without significant differences between the two groups. No significant difference between Angiojet vs. Export was observed in ST-segment resolution >50% and ≥ 70%, in TIMI Flow, TIMI Frame Count and Myocardial Blush Grade before vs. after PPCI and in Infarct Size and Severity., Conclusions: PPCI with thrombus aspiration was effective in both groups of patients, without differences in myocardial reperfusion and necrosis indices. These results could support the routine use of manual devices during PPCI, reserving the more expensive Angiojet in case of manual device failure and persistent or massive intracoronary thrombosis, with favorable implications in terms of cost containment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The study sought to determine the impact of high residual platelet reactivity (HRPR) on long-term cardiac mortality in diabetic patients treated with PCI for CTO. No data exist about the impact of HRPR after 600 mg clopidogrel loading on long-term clinical outcome in patients with diabetes mellitus and treated with percutaneous coronary angioplasty (PCI) for chronic total occlusion (CTO)., Methods: From the Florence CTO-PCI registry, we identified consecutive diabetic patients with available in vitro platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel. HRPR was defined as residual platelet aggregation by 10 μmol/L ADP test ≥70%. The primary end point of the study was long-term cardiac mortality., Results: Two-hundred and three diabetic patients underwent CTO-PCI. The incidence of HRPR was 23%. The 3-year cardiac survival was lower in the HRPR group than the low residual platelet reactivity (LRPR) group (70 ± 7% and 92 ± 3%, respectively; p=0.001). Within the oral antidiabetic patients there were no significant differences in long-term survival between HRPR and LRPR groups. Conversely, the association of insulin therapy and HRPR was related to a dramatic decrease in survival compared to the LRPR group (34 ± 14% vs. 89 ± 4%; p<0.001). At multivariable analysis insulin therapy (HR 4.31; p=0.001) and HRPR (HR 3.26; p=0.004) were significantly related to long-term mortality, while completeness of revascularization was inversely related to cardiac mortality (HR 0.40; p=0.029)., Conclusion: HRPR is a strong marker of increased risk of cardiac death in patients with DM who underwent PCI for CTO., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to investigate the efficacy of prasugrel compared with clopidogrel in clopidogrel nonresponders., Background: Clopidogrel nonresponsiveness is a strong marker of the risk of cardiac death and stent thrombosis after a percutaneous coronary intervention (PCI). It is unknown whether clopidogrel nonresponsiveness is a nonmodifiable risk factor or whether prasugrel with more potent and predictable platelet inhibition as measured by ex vivo techniques is associated with a positive effect on clinical outcome., Methods: The RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt thrombosis) study screened clopidogrel nonresponders after a 600-mg loading dose of clopidogrel. Clopidogrel nonresponders switched to prasugrel (10 mg/day) the day of the PCI, and an adenosine diphosphate (ADP) test (10 μmol/l of ADP) was performed 6 days after the PCI. The primary endpoint was 2-year cardiac mortality. Patient outcome was compared with the RECLOSE-2-ACS study., Results: We screened 1,550 patients, of whom 302 were clopidogrel nonresponders. The result of the ADP test was 77.6 ± 6.2%. After switching to prasugrel, the ADP test result decreased to 47.1 ± 16.8%. The 2-year cardiac mortality rate was 4% in the RECLOSE-3 study and 9.7% in nonresponders of the RECLOSE-2-ACS study (p = 0.007). The definite and probable stent thrombosis rates were 0.7% and 4.4%, respectively (p = 0.004). On multivariable analysis, prasugrel treatment was related to the risk of 2-year cardiac death (hazard ratio: 0.32, p = 0.036)., Conclusions: Clopidogrel nonresponsiveness can be overcome by prasugrel (10 mg/day), and optimal platelet aggregation inhibition on prasugrel treatment is associated with a low rate of long-term cardiac mortality and stent thrombosis., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

No datum is so far available on the relation between age and the acute glucose response to stress in women with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI).We evaluated the age-related differences in the acute glucose response in 373 STEMI women submitted to PCI. The oldest women, when compared to the other age subgroups, showed the higher admission and peak glycemia (P < 0.001 and P < 0.001, respectively) in the lack of differences in insulin, C-peptide, hemoglobin-glycated values and discharge glycemia values. At logistic regression analysis, the following variables were independent predictors of in-Intensive Cardiac Care Unit mortality: age (1-year step) [odds ratio 1.09, 96% confidence interval (CI) 1.04-1.15, P = 0.001], admission glycemia (1g/l step) (odds ratio 2.05, 96% CI 1.35-3.12, P < 0.001). At Cox regression analysis the following variables were associated with 1-year mortality (when adjusted for discharge glycemia): age (1-year step) (hazard ratio 1.13, 95% CI 1.04-1.22, P = 0.005), estimated glomerular filtration rate (1 g/l step) (hazard ratio 0.93, 95% CI 0.90-0.96, P < 0.001).Age affects the acute glucose response to myocardial injury since older women showed the higher admission glucose values and the poorer in-hospital glucose control, in the lack of differences of insulin-resistance incidence. Glucose values were independent predictors of in-hospital mortality, but were not related to long-term survival.

Background: The effect of thrombus aspiration on mortality is still controversial, with results which are often inconsistent in different randomized trials, real world registries and different follow-up duration. The aim of this analysis was to assess the effect on 30-day and 1-year mortality of thrombus aspiration during primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) compared with conventional PCI., Methods: We used data from all the consecutive STEMI patients treated either with conventional PCI or thrombus aspiration between January 1, 2004 and January 1, 2012. Propensity matching score was calculated on the basis of several baseline and procedural characteristics in order to predict the probability for each patient of having been treated with thrombus aspiration. This propensity score analysis was used in order to select a cohort of patients treated with thrombus aspiration matched one-to-one with patients treated with conventional PCI., Results: In total, 744 (53.1%) patients out of 1,400 enrolled were treated with thrombus aspiration. In the matched cohort, at 30-day follow-up 6.3% of patients in the conventional PCI group died compared to 4.7% in the thrombus aspiration group. The unadjusted hazard ratio (HR) for 30-day mortality was 1.01 (95% CI 0.33-3.14, p = 0.985). In the same cohort, 10.7% of patients died at 1-year in the conventional PCI group compared to 5.2% in the thrombus aspiration group. The 1-year unadjusted hazard ratio for mortality was 0.47 (95% CI 0.25-0.90, p = 0.025). The HR changed and was no longer significant after adjustment for differences in the use of glycoprotein (GP) IIb/IIIa inhibitors, lesion pre-dilatation and pre-procedural TIMI flow: 0.71 (95% CI 0.36-1.39, p = 0.322)., Conclusions: Thrombus aspiration does not influence 30-day mortality, however it is associa­ted with 1-year survival benefit. GP IIb/IIIa inhibitors and thrombus aspiration may have an important synergistic role in leading to this long-term benefit.

We evaluated the relationship between admission renal function (as assessed by estimated glomerular filtration rate (eGFR)), hyperglycemia, and acute insulin resistance, indicated by the homeostatic model assessment (HOMA) index, and their impact on long-term prognosis in 825 consecutive patients with ST-elevation myocardial infarction (STEMI) without previously known diabetes who underwent primary percutaneous coronary intervention (PCI). Admission eGFR showed a significant indirect correlation with admission glycemia (Spearman's ρ -0.23, P < 0.001) and insulin values (Spearman's ρ -0.11, P = 0.002). The incidence of patients with admission glycemia ≥140 mg/dl was significantly higher in patients with eGFR <60 ml/min/m(2) (P < 0.001) as well as the incidence of HOMA positivity (P = 0.002). According to our data, a relationship between renal function and glucose values and acute insulin resistance in the early phase of STEMI was detectable, since a significant, indirect correlation between eGFR, insulin values, and glycemia was observed. Patients with renal dysfunction (eGFR <60 ml/min/1.73 m(2)) exhibited higher glucose values and a higher incidence of acute insulin resistance (as assessed by HOMA index) than those with normal renal function (eGFR ≥60 ml/min/1.73 m(2)). The prognostic role of glucose values for 1-year mortality was confined to patients with eGFR ≥60 ml/min/m(2), who represent the large part of our population and are thought to be at lower risk. In these patients, an independent relationship between 1-year mortality and glucose values was detectable not only for admission glycemia but also for glucose values measured at discharge.

Background: In acute coronary syndrome (ACS) patients older than 75 years old, prasugrel 10 mg maintenance therapy has shown less clinical efficacy and higher risk of bleeding. In patients older than 75 years, a prasugrel dose of 5 mg should be used if treatment is deemed necessary., Objective: The aim of this study was to compare platelet reactivity and outcomes in elderly patients receiving prasugrel 5mg therapy with non-elderly patients receiving prasugrel 10 mg therapy., Methods and Results: Consecutive ACS patients undergoing percutaneous coronary intervention (PCI) treated with prasugrel were included. Of 718 patients, 228 (32%) had ≥75 years and received prasugrel 5 mg/day. Residual platelet reactivity (RPR) was 47±18% and 36±16% in the elderly and non-elderly group, respectively (p=0.001). High RPR (≥70%) was found in 9% and 2% (p=0.0001) in elderly and non-elderly patients, respectively. In the 6-month follow-up, there was no difference in mortality, stent thrombosis, and reinfarction rates between the 2 groups but a higher rate of TIMI minor bleeding (7.9% vs 2.4%; p=0.001) in elderly as compared with younger patients. Age≥75 years was independently associated with bleeding events (HR 2.162 [1.105-4.229]; p=0.024)., Conclusions: Elderly patients receiving prasugrel 5mg are more likely to experience high RPR than younger patients treated by prasugrel 10 mg. Despite the use of a reduced prasugrel maintenance dose and a higher level of RPR, elderly patients show increased risk of bleeding during prasugrel therapy as compared to younger patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Application of percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) is suboptimal in older frail individuals. This study was conducted to verify if background risk is a risk factor for underuse and diminished effectiveness of PCI in older patients., Methods: An observational cohort study was conducted using data from the Acute Myocardial Infarction in Florence 2 registry, including all ACS hospitalised in 1 year in the area of Florence, Italy. Patients aged 75+ years were selected, whose background risk was stratified with the Silver Code (SC), a validated tool predicting mortality based upon administrative data. Multivariable OR for PCI application and HR for 1-year mortality by PCI usage were calculated., Results: In 698 patients (358 women, mean age 83 years), of whom 176 had ST-segment elevation myocardial infarction (STEMI), for each point increase in SC score the odds for application of PCI decreased by 11%, whereas the hazard of 1-year mortality increased by 10%, adjusting for positive and negative predictors. PCI reduced 1-year mortality progressively more with increasing SC, with HR (95% CI) of 0.8 (0.19 to 1.21), 0.41 (0.18 to 0.45), 0.41 (0.23 to 0.74) and 0.26 (0.14 to 0.48) for SC of 0-3, 4-6, 7-10 and 11+., Conclusions: Application of PCI in older ACS patients decreased with increasing background risk. This therapeutic attitude could not be justified by decreasing effectiveness of PCI in more compromised patients: conversely, application of PCI was associated with a long-term survival advantage that increased progressively with background risk, as expressed by SC., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

There are very few clinical data concerning the safety of switching from clopidogrel to prasugrel in patients undergoing coronary stenting. However, in the daily activity, clinicians face the decision of switching patients at high-risk of thrombotic events from clopidogrel to prasugrel. Thus, we sought to evaluate clinical events in patients undergoing coronary stent implantation and prasugrel therapy with (SWITCH group) or without (NAÏVE group) prior clopidogrel therapy. A total of 454 patients with stable or unstable coronary artery disease, aged 70 ± 10 years, underwent non-emergent stent implantation and received prasugrel therapy. Of these, 315 (69 %) patients received clopidogrel before switching to prasugrel therapy. In 239 patients with high residual platelet reactivity (HRPR) on clopidogrel, prasugrel decreased platelet aggregation from 72 ± 11 to 43 ± 16 % (p < 0.001). There was no difference in in-hospital major or minor TIMI bleeding (2.8 vs. 4.3 %; p = 0.411) between the SWITCH and NAÏVE groups as well as in mortality, acute stent thrombosis, reinfarction and stroke rates. At multivariable analysis, independent predictors of bleeding were female gender (OR 5.56 [1.41-19.88] p = 0.014) and chronic renal failure (OR 6.27 [1.59-21.65] p = 0.009), but switching therapy did not. This result was confirmed after switching propensity score adjustment (c-statistic 0.81; Hosmer-Lemeshow test p = 860). Switching from clopidogrel to prasugrel in patients undergoing non-emergent coronary stent implantation seems to be tolerated with no overt signs of increased bleeding.

Unlabelled: In ST-elevation myocardial infarction (STEMI) patients, residual platelet reactivity soon after a loading dose (LD) of prasugrel or ticagrelor is higher than that reported for healthy volunteers or subjects with stable coronary artery disease; and the majority of primary percutaneous coronary intervention (PPCI) procedures with bivalirudin monotherapy are performed without proper platelet inhibition. However, ticagrelor LD is just the daily dose, whereas prasugrel LD is 6-fold the long-term daily dose. We hypothesized that an increased ticagrelor LD may result in a faster and more effective platelet inhibition as compared with the standard prasugrel LD., Methods: Fifty patients with STEMI, pretreated with intravenous aspirin, undergoing PPCI were randomized to receive prasugrel 60-mg LD (n = 25) or ticagrelor 360-mg LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD., Results: At the time of LD, 90% of enrolled patients had an aspirin reactivity unit value <550. P2Y12 reaction units 1 hour after the LD (study primary end point) were 236 (129-289) and 248 (115-304) in the prasugrel and ticagrelor group, respectively (P = .899). High residual platelet reactivity (P2Y12 reaction units ≥240) was found in 43% and 56% of patients (P = .386) at 1 hour and in 30% and 32% of patients (P = .907) at 2 hours, respectively. There was no significant difference in bleeding, arrhythmias, or dyspnea episodes in the 2 groups., Conclusions: In patients with STEMI undergoing PPCI, double (360 mg) ticagrelor LD failed to achieve a faster and more intense platelet inhibition as compared with the standard prasugrel LD. Intravenously administered aspirin allowed to achieve a very early inhibition of acid arachidonic pathway., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background and Purpose: Although several studies reported that drug-eluting stents (DES) are able to reduce restenosis incidence without increasing mortality, concerns still exist about their safety in ST-segment elevation myocardial infarction (STEMI) patients mainly for a possible higher rate of in-stent thrombosis. Recent evidence suggests a better safety profile of second-generation DES, but data on their outcome in STEMI are still poor. In this study we evaluated the impact on mortality and target lesion revascularization (TLR) of DES or bare metal stent (BMS) implantation in STEMI patients submitted to primary angioplasty., Methods and Subjects: We analyzed mortality and TLR in 1150 STEMI patients during a mean 43-month follow-up after DES (44.6%) or BMS (55.4%) implantation. A propensity score method was used to minimize bias. During follow-up, 223 deaths occurred., Essential Results: Unadjusted for potential confounders, DES implantation was associated with a significant reduction in all-cause mortality [hazard ratio (HR) 0.40; 95%CI 0.30-0.54] and TLR (HR 0.55; 95%CI 0.36-0.86); this latter was confirmed after propensity score analysis (HR 0.39; 95%CI 0.21-0.67). Second- (n=179) vs. first- (n=337) generation DES showed a further reduction in TLR (HR 0.17; 95%CI 0.05-0.57). Adjusted analyses showed a significant reduction in the combined end-point of all-cause mortality or TLR after both first- and second-generation DES vs. BMS implantation with a trend to a lower risk for second- vs. first-generation DES., Principal Conclusions: DES implantation in STEMI patients showed a significant reduction in TLR and in the combined endpoint of TLR or mortality. Second-generation DES showed a more protective effect on the combined endpoint, suggesting that they would be preferred in this setting., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Previous studies analyzing the impact of hypertension (HTN) on myocardial infarction (MI) outcome reached conflicting results and scarce data are available in patients treated with percutaneous coronary intervention (PCI). In this study the prognostic impact of HTN history in ST-elevation MI (STEMI) and Non-STEMI (NSTEMI) patients treated with PCI was analyzed. We compared characteristics of 1,031 STEMI and 437 NSTEMI patients, in relation to the presence of HTN. Median follow-up duration was 40.2 months. HTN was significantly higher in NSTEMI vs. STEMI patients (p < 0.001). NSTEMI patients were older, with higher values of left ventricular ejection fraction (LVEF) and more frequently with previous myocardial revascularization than STEMI patients either among hypertensives and non-hypertensives. At univariate analysis HTN resulted associated with long-term mortality in STEMI but not in NSTEMI patients. At multivariate analysis HTN was not associated with either in-hospital and long-term mortality in both NSTEMI and STEMI group. In conclusion, in the PCI era HTN does not influence MI patients prognosis; other factors, such as age, admission LVEF, coronary disease extension, previous MI and creatinine levels are independently associated with MI patients outcome even though this should not discourage from a strict control of HTN after the acute event.

An 80-year-old diabetic man with severe aortic stenosis was admitted to our hospital for cardiogenic shock complicating non-ST-elevation myocardial infarction. Echocardiographic evaluation showed also a severe degree of both left ventricular dysfunction and mitral regurgitation. The patient was initially stabilized with inotropes and mechanical ventilation was necessary because of concurrent pulmonary edema. The day after, he was submitted to coronary angiography showing bivessel coronary disease. Given the high estimated operative risk, the patient was treated with angioplasty and bare metal stent implantation on both right coronary and circumflex artery; contemporarily, balloon aortic valvuloplasty (BAV) was performed with anterograde technique, obtaining a significant increase in planimetric valve area and reduction in transvalvular peak gradient. Few days after the procedure echocardiogram showed an increase in left ventricular ejection fraction, moderate aortic stenosis with mild regurgitation and moderate mitral regurgitation. Hemodynamic and clinical stabilization were also obtained, allowing amine support discontinuation and weaning from mechanical ventilation. At three months follow-up, the patient reported a further clinical improvement from discharge, and echocardiographic evaluation showed moderate aortic stenosis and an additional increase in left ventricular function and decrease in mitral regurgitation degree. In conclusion, combined BAV and coronary angioplasty were associated in our patient with hemodynamic and clinical stabilization as well as with a significant reduction in transvalvular aortic gradient and mitral regurgitation and an increase in left ventricular ejection fraction both in-hospital and at three month follow-up; this case suggests that these procedures are feasible even in hemodynamically unstable patients and are associated with a significant improvement in quality of life.

Background: Although controversial, using prophylactic intra-aortic balloon pump (IABP) in patients undergoing high-risk percutaneous coronary intervention (PCI) has been reported to be effective by numerous registry studies. However, conflicting findings were observed in observational studies (Obs.) and randomised controlled trials (RCTs)., Objective: The purpose of this meta-analysis was to assess the impact of IABP on in-hospital deaths, major adverse cardiovascular events (MACCE), access-site complications and stroke in high-risk PCI cases from Obs. and RCTs published from 1st January, 1990 to 31st March, 2012 and indexed in PubMed., Methods and Results: We retrieved 1125 studies from the database; 11 studies compared the effects of IABP support, i.e., prophylactic administration (P-IABP) vs. no support (No-IABP), in high-risk patients undergoing PCI. These studies were included in the meta-analysis. We then calculated risk ratios (RRs) and risk differences (RDs) between the two groups of patients (P-IABP vs. No-IABP). We did not observe significant in-hospital mortality, MACCE, access-site complications or stroke differences in the RRs and RDs of the two groups., Conclusions: The results suggest that PCI plus P-IABP support does not result in reduced in-hospital mortality or MACCE nor in significant higher access-site complications or stroke incidence compared with PCI alone in patients at high risk for peri-procedural PCI complications., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aim: Limited data are available on the safety and outcome of percutaneous coronary intervention (PCI) in elderly patients with ST elevation myocardial infarction (STEMI), as elderly patients are under-represented in randomized trials., Methods: We therefore aimed at assessing the trends in mortality rates (both at short-term and at 1-year follow up) in an unselected cohort of 404 STEMI patients aged ≥ 75 years all submitted to primary PCI and consecutively admitted to our Intensive Cardiac Care Unit from 2004 to 2010., Results: In the first period (2004-2006), 202 patients (202/661, 30.6%) were aged ≥ 75 years, whereas in the second period (2007-2010), 203 patients (203/607, 33.4%) were aged ≥ 75 years. In the second period, STEMI patients were older (P<0.001), more diabetic (P<0.001) and with a higher incidence of comorbidities (P<0.001). A significantly lower use of intra-aortic balloon pump was observed, together with a reduced rate of bleeding, whereas the incidence of worsening renal function significantly increased (P=0.011). No difference was observed in the length of stay and in mortality rate (both in-hospital and 1-year post-discharge) between the first and the second period., Conclusions: According to our data, patients aged ≥ 75 years are characterized by an increasing number of comorbidities (in particular, a higher incidence of diabetes). Over a 6-year period, despite a more advanced age, early mortality (and length of stay) remained unchanged (probably thanks to a significant reduction in bleeding events), and no difference was observed in 1-year post-discharge mortality in these patients., (© 2012 Japan Geriatrics Society.)

Objectives: This study sought to compare the action of prasugrel and ticagrelor in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI)., Background: It has been documented that prasugrel and ticagrelor are able to provide effective platelet inhibition 2 h after a loading dose (LD). However, the pharmacodynamic measurements after prasugrel and ticagrelor LD have been provided by assessing only healthy volunteers or subjects with stable coronary artery disease., Methods: Fifty patients with STEMI undergoing PPCI with bivalirudin monotherapy were randomized to receive 60 mg prasugrel LD (n = 25) or 180 mg ticagrelor LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 2, 4, 8, and 12 h after LD., Results: Platelet reactivity units (PRU) 2 h after the LD (study primary endpoint) were 217 (12 to 279) and 275 (88 to 305) in the prasugrel and ticagrelor groups, respectively (p = NS), satisfying pre-specified noninferiority criteria. High residual platelet reactivity (HRPR) (PRU ≥240) was found in 44% and 60% of patients (p = 0.258) at 2 h. The mean time to achieve a PRU <240 was 3 ± 2 h and 5 ± 4 h in the prasugrel and ticagrelor groups, respectively. The independent predictors of HRPR at 2 h were morphine use (odds ratio: 5.29; 95% confidence interval: 1.44 to 19.49; p = 0.012) and baseline PRU value (odds ratio: 1.014; 95% confidence interval: 1.00 to 1.03; p = 0.046)., Conclusions: In patients with STEMI, prasugrel showed to be noninferior as compared with ticagrelor in terms of residual platelet reactivity 2 h after the LD. The 2 drugs provide an effective platelet inhibition 2 h after the LD in only a half of patients, and at least 4 h are required to achieve an effective platelet inhibition in the majority of patients. Morphine use is associated with a delayed activity of these agents. (Rapid Activity of Platelet Inhibitor Drugs Study, NCT01510171)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous coronary intervention (PCI) requires the use of iodinated contrast medium and consequently poses the risk of contrast-induced nephropathy (CIN), which can negatively impact on outcome. Patients with chronic kidney disease (CKD) are at particularly high risk of CIN. In this study, we investigated the role of continuous renal replacement therapy (CRRT) performed before and after versus only after PCI in patients with CKD., Methods: We studied 46 consecutive patients with CKD (mean creatinine >2 mg/dL) submitted to PCI: 21 (mean creatinine 2.7 ± 1.6 mg/dL) treated with CRRT only after PCI (CRRTpost) and 25 (mean creatinine 3.0 ± 1.3 mg/dL) with CRRT before and after PCI (CRRTpre-post). CRRT was performed with hemofiltration (creatinine <3 mg/dL) or hemodiafiltration (creatinine >3 mg/dL), initiated 6-8 hours before PCI and re-started immediately post PCI for 18-24 hours., Results: Creatinine showed a greater reduction in CRRTpre-post (2.4 ± 1.0 vs. 3.0 ± 1.3 mg/dL; P=.002) with respect to CRRTpost (2.6 ± 1.3 vs 2.7 ± 1.6 mg/dL; P=.667). At median 14.7-month follow-up, CKD worsened in 3 patients (12%) of CRRTpre-post and in 9 (43%) of CRRTpost (P=.042). Kaplan-Meier analysis at 18 months showed a significantly higher overall mortality in patients treated with CRRTpre-post vs. CRRTpost (P=.041), which became even more significant during the entire follow-up period (P=.026) and an increase in cardiovascular deaths (5 vs. 0, respectively)., Conclusions: Our results suggest that in CKD patients undergoing PCI, CRRT performed before and after is more effective in preventing a further deterioration of renal function and is associated with an improved long-term outcome when compared to CRRT performed only after.

Background: So far, few data have been available on the incidence and outcome of patients with acute myocardial infarction (MI) requiring mechanical ventilation (MV). The aim of the study was to assess the clinical and prognostic impact of MV at short and long term in 106 patients with ST elevation MI (STEMI) requiring mechanical ventilation., Results: The incidence of mechanical ventilation was 7.6%. Reasons for intubation were as follows: cardiogenic shock in 64 (60.4%) patients, ventricular fibrillation in 32 (30.1%) patients and acute pulmonary edema in 10 (9.5%) patients. Patients submitted to MV were older (p = 0.016), more frequently had a previous percutaneous coronary intervention (PCI;p = 0.014) and a previous MI (p = 0.001). A higher in-Intensive Cardiac Care Unit death was observed in MV patients (44.3% vs. 1.5%, p < 0.001), as well as a higher mortality at follow-up (36.7% vs. 14.8%, p < 0.001). MV was associated with higher mortality rates both at short and long term., Conclusions: In a large series of consecutive STEMI patients submitted to MV, the need of MV is a strong prognostic indicator of mortality both at short and long term. Among mechanically ventilated STEMI patients infarct size (as inferred by TnI values) and PCI failure were independent predictors of early death, while the duration of MV was related to death at longterm.

Aims: To assess the impact of microalbuminuria on the development of acute kidney injury and to investigate its prognostic role at long term follow-up in 526 consecutive patients with ST elevation myocardial infarction without previously known diabetes., Methods: Microalbuminuria was measured using immunonephelemetry in the urine collected in the night., Results: Patients with microalbuminuria were older (p = 0.013). They showed higher values of peak glycemia (p = 0.017), peak Tn I (p < 0.001), NT-pro BNP (p = 0.020), ESR (p = 0.003), CRP (p = 0.020), and leukocyte count (p < 0.001). Lower eGFR was observed in patients with microalbuminuria both on admission and during ICCU stay (p = 0.048 and p = 0.003, respectively). A positive correlation was observed between CRP and microalbuminuria (Spearman's rho 0.114, p = 0.024). The composite end point was observed in 73 patients (18 patients died and 59 patients developed acute kidney injury). At multivariable regression analysis, microalbuminuria was an independent predictor of acute kidney injury. At follow-up [42.6 (25th-75th percentile, 17.5-56.8) months], Kaplan-Meier curve analysis showed that patients with microalbuminuria had a lower survival rate in respect to patients without microalbuminuria. Cox regression analysis documented that microalbuminuria was an independent predictor of long term mortality (HR: 1.089; 97% CI 1.036-1.145; p < 0.001)., Conclusions: In a large series of STEMI patients without previously known diabetes submitted to PCI, microalbuminuria, as a marker of endothelial permeability following higher systemic inflammatory activation and larger infarct lesions, is an independent predictor for the development acute kidney injury. Furthermore, microalbuminuria identifies a subset of patients at higher risk for long term mortality.

Aims: Long-term prognosis of ST segment elevation myocardial infarction (STEMI) in the era of primary percutaneous coronary intervention (pPCI) remains relatively poorly investigated in unselected patients. This study analyzed 8-year follow-up of STEMI patients enrolled in the Florence Acute Myocardial Infarction Registry, a population-based, observational study performed in Italy in 2000-2001., Methods: The prognostic effect of pPCI adjusted for clinical and demographic characteristics on a composite end-point of new myocardial infraction, urgent revascularization or death, and on all-cause mortality separately, was assessed in multivariable Cox analysis, calculating hazard ratios and 95% confidence intervals. This analysis is concerned with 875 STEMI patients (mean age 70.6 ± 12.9 years), treated with pPCI (459) or conservatively (416)., Results: After 8 years, 59% of patients had experienced the composite end-point and 49% had died. The multivariable analysis showed a significantly better prognosis in patients receiving pPCI (hazard ratio 0.72, P = 0.001), evident also in the 645 patients who were event-free after the first year of follow-up (hazard ratio 0.72, P = 0.010). Other independent prognostic factors were advanced age, Killip class greater than 1, some cardiovascular or noncardiovascular comorbidities, in-hospital cardiogenic shock, ejection fraction less than 30%, and treatment with aspirin and statin during hospitalization. The beneficial effect of pPCI observed both in cases younger (adjusted hazard ratio 0.65, P = 0.013) and older than 75 years (adjusted hazard ratio 0.65, P = 0.001) was also confirmed considering as outcome all-cause mortality only., Conclusions: In unselected STEMI patients, survival advantage from pPCI extends for a long term (8 years). This survival advantage is maintained at advanced ages, thus enforcing the importance of improving delivery of appropriate care to older STEMI patients.

Abstract: The prognostic implications of NT-proBNP measured on admission in patients with the ST-elevation myocardial infarction (STEMI) are not so far well elucidated. The present investigation, performed in 198 STEMI patients submitted to percutaneous coronary intervention (PCI), was aimed at assessing the prognostic value of NT-proBNP measured on admission to Intensive Cardiac Care Unit (ICCU) and its relation with the extension of myocardial infarction (indicated by cardiac biomarkers and ejection fraction) and inflammatory markers (C-reactive protein — CRP, erythrocyte sedimentation rate — ESR, leucocytes, fibrinogen). All patients who died during ICCU stay had increased values of NT-proBNP. Each quartile of NT-proBNP resulted directly correlated with age, heart rate, peak Tn I, admission creatinine serum levels, ESR, fibrinogen, and inversely correlated with ejection fraction. At backward logistic regression analysis, NT-proBNP values showed a significative correlation with peak Tn I (OR 1.013; 95% CI 1.001–1.025; p =0.036), and CRP positive (OR 6.450; 95% CI 1.714–24.272; p =0.006); age was close to reaching statistical significance (OR 1.043; 95% CI 0.999–1.089; p =0.055). At long term-follow-up NT-proBNP lacks any prognostic role in predicting adverse events such as hospitalization for rePCI, re-infarction and heart failure. Kaplan–Meier curves showed that all patients dead at follow-up were in the highest NT-proBNP quartiles. [Copyright &y& Elsevier]

Abstract: Response variability to antiplatelet treatment has been described and the widespread use of acetylsalicylic acid (ASA) and clopidogrel requires clarification of the residual platelet reactivity (RPR). Various glycoprotein Ia (GpIa) polymorphisms have been investigated, but their influence on platelet reactivity in myocardial infarction (MI) patients undergoing percutaneous coronary intervention (PCI) on dual antiplatelet treatment is not still elucidated. Aim of this study was to evaluate the effect of C807T, G873A and T837C polymorphisms of GpIa on modulating platelet function in MI patients on dual antiplatelet treatment undergoing PCI. We measured platelet function by both a point-of-care assay (PFA100) and platelet-rich-plasma aggregation in 289 MI patients undergoing PCI and receiving dual antiplatelet treatment. Our data show that C807T/G873A polymorphisms, but not T837C, are associated with higher platelet reactivity. Carriers of the 807T/873A allele had significantly higher platelet aggregation values after arachidonic acid (AA) and collagen stimuli and, even if they did not reach the statistical significance, after 2 and 10μM ADP stimuli; 807T/873A allele carriers had also significantly shorter closure times on PFA100/epinephrine membranes. At the multiple analyses, C807T/G873A polymorphisms resulted an independent risk factor for RPR defined by both AA induced platelet aggregation (OR=3.0, 95%CI 1.17–7.89, p =0.022) or by PFA100/epinephrine (OR=4.1, 95%CI 1.53–10.89, p =0.005). In conclusion, this study shows the 807T/873A allele of the GpIa gene is an independent risk factor for the RPR on dual antiplatelet treatment, and extends, in a larger acute coronary syndrome population, the observation that the 807T/873A allele is associated with higher platelet reactivity. [Copyright &y& Elsevier]

Abstract: Objectives: The mortality of patients with cardiogenic shock (CS) complicating ST elevation acute myocardial infarction (STEMI) remains high, despite early revascularization. Current knowledge of predictors of death is limited. Background: The pathophysiologic understanding of CS after acute myocardial infarction has shifted from a mere hemodynamic disorder to a more complex approach including imbalance in metabolic functions. Methods: In 45 consecutive patients (71.4±13 years) with CS complicating STEMI treated with primary percutaneous coronary intervention (PCI) serum levels of lactate, glucose and uric acid on coronary care unit (CCU) admission were measured. The end-point was in-hospital death. Results: The following parameters, on CCU admission, were univariate predictors of in-hospital mortality: serum glucose >200 mg/dl (OR=11.3, p =0.002), serum creatinine >1.5 mg/dl (OR=12.7, p =0.003), uric acid >6.5 mg/dl (OR=6.7, p =0.016), lactate >6.5 mmol/l (OR=54, p <0.0001), age ≥75 years (OR=8.5, p =0.002), history of hypertension (OR=8.3, p =0.003) and TIMI flow post PCI ≤ 2 (OR=12.9, p =0.02). At multivariate analysis, after adjustment for sex, age, hypertension and diabetes, lactate >6.5 mmol/l and TIMI flow post PCI ≤ 2 were still independent predictors of in-hospital mortality (OR=295, p =0.01; OR=19.5, p =0.04, respectively). Conclusions: Hyperlactatemia, hyperglycemia and increased levels of uric acid on CCU admission are univariate predictors of in-hospital death. Moreover, at multivariate analysis, hyperlactatemia (>6.5 mmol/l) is an independent indicator of in-hospital death in CS patients complicating STEMI. [Copyright &y& Elsevier]