Andrea D'Ambrosio

Point-of-Care Measurement of Clopidogrel Responsiveness Predicts Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention : Results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) Study

OBJECTIVES The aim of this study was to evaluate the correlation of point-of-care measurement of platelet inhibition with clinical outcome in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND Individual variability of clopidogrel response might influence results of PCI. METHODS A total of 160 patients receiving clopidogrel before PCI were prospectively enrolled. Platelet reactivity was measured by the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, California). Primary end point was 30-day occurrence of major adverse cardiac events (MACE) according to quartile distribution of P2Y12 reaction units (PRU). RESULTS Primary end point occurred more frequently in patients with pre-procedural PRU levels in the fourth quartile versus those in the lowest quartile (20% vs. 3%; p=0.034), and it was entirely due to periprocedural myocardial infarction (MI). Mean PRU absolute levels were higher in patients with periprocedural MI (258+/-53 vs. 219+/-69 in patients without; p=0.030). On multivariable analysis pre-PCI PRU levels in the fourth quartile were associated with 6-fold increased risk of 30-day MACE (odds ratio: 6.1; 95% confidence interval: 1.1 to 18.3, p=0.033). By receiver-operating characteristic curve analysis, the optimal cut-off for the primary end point was a pre-PCI PRU value>or=240 (area under the curve: 0.69; 95% confidence interval: 0.56 to 0.81, p=0.016). CONCLUSIONS This study indicates that high pre-PCI platelet reactivity might predict 30-day events. Use of a rapid point-of-care assay for monitoring residual platelet reactivity after clopidogrel administration might help identify patients in whom individualized antiplatelet strategies might be indicated with coronary intervention.

The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review

The World Health Organization/International Society and Federation of Cardiology (WHO/ISFC) task force on the definition and classification of cardiomyopathies recently updated and reclassified heart muscle diseases.1 Myocarditis was defined as “an inflammatory disease of the myocardium . . . diagnosed by established histological, immunological, and immunohistochemical criteria.” Three distinct forms of inflammatory cardiomyopathy (that is, myocarditis associated with cardiac dysfunction) are recognised: idiopathic, autoimmune, and infectious. Various infectious factors may cause myocarditis, but viral agents, especially coxsackie group B viruses, are most commonly associated with this disease.2 Myocarditis has been recognised for almost two centuries, since Corvisart first described this disease in clinical terms in 1812,3 but in the last three decades there has been renewed interest in the inflammatory process in the myocardium. The reasons for this are multiple: the introduction of endomyocardial biopsy for in vivo diagnosis (the disease was often overdiagnosed in the past on purely clinical grounds)4; related efforts to produce standardised criteria for histological diagnosis (the Dallas criteria; fig 1)5; better understanding of cardiotropic viruses, studied in animal models of myocarditis,6 leading to new insights into the immunological mechanisms of the disease (fig2)7 and potential treatments in humans8; and lastly—and perhaps most interestingly—the finding of a possible causal relation between viral myocarditis and dilated cardiomyopathy,9 a major cause of congestive heart failure in western countries. Figure 1 Histological section of active lymphocytic myocarditis according to the Dallas criteria. A dense infiltrate of lymphocytes in close contact with damaged and necrotic myocytes is evident (haematoxylin and eosin × 100). Figure 2 CD4RO positive T lymphocytic cellular infiltrates in a diffuse pattern (× 40). Despite numerous published reports on this disease, the natural history of acute myocarditis is still poorly understood, despite the development of immunological …

Short-term, high-dose Atorvastatin pretreatment to prevent contrast-induced nephropathy in patients with acute coronary syndromes undergoing percutaneous coronary intervention (from the ARMYDA-CIN [atorvastatin for reduction of myocardial damage during angioplasty--contrast-induced nephropathy] trial.

Contrast-induced nephropathy (CIN) impairs clinical outcome in patients undergoing angiographic procedures. The aim of this study was to investigate whether short-term high-dose atorvastatin load decreases the incidence of CIN after percutaneous coronary intervention (PCI). Statin-naive patients with acute coronary syndrome undergoing PCI (n = 241) randomly received atorvastatin (80 mg 12 hours before intervention with another 40-mg preprocedure dose, n = 120) or placebo (n = 121). All patients had long-term atorvastatin treatment thereafter (40 mg/day). Primary end point was incidence of CIN defined as postintervention increase in serum creatinine ≥0.5 mg/dl or >25% from baseline. Five percent of patients in the atorvastatin arm developed CIN versus 13.2% of those in the placebo arm (p = 0.046). In the atorvastatin group, postprocedure serum creatinine was significantly lower (1.06 ± 0.35 vs 1.12 ± 0.27 mg/dl in placebo, p = 0.01), creatinine clearance was decreased (80.1 ± 32.2 vs 72.0 ± 26.6 ml/min, p = 0.034), and C-reactive protein peak levels after intervention were decreased (8.4 ± 10.5 vs 13.1 ± 20.8 mg/l, p = 0.01). Multivariable analysis showed that atorvastatin pretreatment was independently associated with a decreased risk of CIN (odds ratios 0.34, 95% confidence interval 0.12 to 0.97, p = 0.043). Prevention of CIN with atorvastatin was paralleled by a shorter hospital stay (p = 0.007). In conclusion, short-term pretreatment with high-dose atorvastatin load prevents CIN and shortens hospital stay in patients with acute coronary syndrome undergoing PCI; anti-inflammatory effects may be involved in this renal protection. These results lend further support to early use of high-dose statins as adjuvant pharmacologic therapy before percutaneous coronary revascularization.

Percutaneous coronary intervention utilizing a new endothelial progenitor cells antibody-coated stent: a prospective single-center registry in high-risk patients.

To prospectively evaluate the outcome with circulating endothelial progenitor cell (EPC) capture stent implantation in a cohort of consecutive patients with high‐risk angiographic and/or clinical features.

A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity for Outcome Validation Effort) study.

OBJECTIVES This study sought to validate the ability of the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) in predicting both ischemic and bleeding events after elective percutaneous coronary intervention (PCI). BACKGROUND High and low levels of platelet reactivity are associated with ischemic and bleeding events, respectively, after PCI. METHODS A total of 732 patients on dual antiplatelet therapy undergoing elective PCI were recruited. Platelet reactivity was measured before PCI. The primary endpoint was the 30-day incidence of net adverse clinical events (NACE), defined as the occurrence of ischemic or bleeding events, in relation to P2Y(12) reaction unit (PRU) distribution. RESULTS At receiver-operating characteristic curve analysis, PRU values could significantly discriminate between patients with and without bleeding events (area under the curve [AUC]: 0.72; 95% confidence interval [CI]: 0.65 to 0.80; p < 0.0001) and those with and without ischemic events (AUC: 0.68; 95% CI: 0.61 to 0.76; p < 0.0001). The optimal cutoffs for bleeding (PRU ≤ 178) and ischemic events (PRU ≥ 239) were used to define 3 groups: low platelet reactivity (LPR) (LPR = PRU ≤ 178), normal platelet reactivity (NPR) (NPR = PRU 179 to 238), and high platelet reactivity (HPR) (HPR = PRU ≥ 239). The incidence of NACE was 14.1% in the LPR group, 7.8% in the NPR group (p = 0.025 vs. LPR group), and 15.4% in the HPR group (p = 0.005 vs. NPR group). At multivariate analysis, PRU values in the NPR group were an independent predictor of reduced risk of 30-day NACE (odds ratio: 0.47, 95% CI: 0.27 to 0.81). CONCLUSIONS A therapeutic window for platelet reactivity measured with the VerifyNow P2Y12 assay can be identified using specific thresholds that define a group of patients at lower risk for both ischemic and bleeding events. Adjunctive measures may be beneficial in patients with higher or lower platelet reactivity in order to improve clinical outcomes after PCI.

Comparison of Platelet Reactivity and Periprocedural Outcomes in Patients With Versus Without Diabetes Mellitus and Treated With Clopidogrel and Percutaneous Coronary Intervention

The effect of periprocedural platelet reactivity and clinical outcomes in diabetic patients taking clopidogrel and undergoing percutaneous coronary intervention (PCI) is unclear. The aim of the present study was to prospectively evaluate the influence of diabetes mellitus (DM) on platelet reactivity measured by the VerifyNow P2Y12 assay and on periprocedural outcomes in patients receiving clopidogrel and undergoing PCI. A total of 285 consecutive clopidogrel-treated patients undergoing elective PCI were included. Platelet function analysis was performed using the VerifyNow P2Y12 assay. High platelet reactivity (HPR) after clopidogrel was defined as a platelet reaction unit value > or =240. Cardiac biomarkers were measured before and 8 and 24 hours after intervention. Patients with DM had significantly higher platelet reactivity before PCI compared to nondiabetics (214 +/- 83 vs 193 +/- 68 platelet reaction units, p = 0.02). HPR was more frequently observed in diabetics (36% vs 22%, p = 0.01) before PCI. Patients with DM had an increased incidence of periprocedural myocardial infarction (MI; 11% vs 4%, p = 0.04). When the entire population was divided by the presence or absence of DM and HPR, patients with DM and HPR presented the highest incidence of periprocedural MI (p for trend = 0.0008). HPR was an independent predictor of periprocedural MI (odds ratio 8.34, 95% confidence interval 2.60 to 26.76, p = 0.0003). In conclusion, patients with DM undergoing PCI have higher platelet reactivity at the time of PCI despite adequate clopidogrel pretreatment and subsequently worse periprocedural outcomes. Point-of-care platelet function testing may help to identify patients at higher risk of periprocedural MI.

Point-of-care assessment of platelet reactivity after clopidogrel to predict myonecrosis in patients undergoing percutaneous coronary intervention.

OBJECTIVES We sought to evaluate the influence of platelet reactivity after clopidogrel, as assessed by the VerifyNow point-of-care assay (Accumetrics, San Diego, California), on myonecrosis in low-to-intermediate risk patients undergoing percutaneous coronary intervention (PCI). BACKGROUND Inadequate platelet inhibition at the time of PCI is associated with a higher risk of recurrent ischemic events. METHODS A total of 250 consecutive biomarker-negative patients treated with clopidogrel and undergoing elective PCI were enrolled. Cardiac biomarkers (creatine kinase-myocardial band and troponin I) were measured before and 8 and 24 h after intervention. Platelet reactivity after clopidogrel was assessed immediately before PCI by the VerifyNow P2Y12 point-of-care assay. High platelet reactivity (HPR) after clopidogrel was defined as a platelet reaction unit value > or =240. RESULTS Patients with HPR (31% of the overall population) showed more frequent myonecrosis, with statistical significance with regard to creatine kinase-myocardial band elevation (35% vs. 20%; p = 0.011), and by trend with regard to troponin-I elevation (47% vs. 35%; p = 0.059). Incidence of periprocedural myocardial infarction was higher in patients with HPR, both by creatine kinase-myocardial band (13% vs. 4%; p = 0.011) and troponin-I definition (32% vs. 19%; p = 0.019). By multivariable analysis, HPR was an independent predictor of periprocedural myocardial infarction. CONCLUSIONS Easily assessed by a point-of-care assay, HPR after clopidogrel is a frequent finding and is associated with increased risk of myonecrosis in low-to-intermediate risk patients undergoing planned PCI.

Strategies of Clopidogrel Load and Atorvastatin Reload to Prevent Ischemic Cerebral Events in Patients Undergoing Protected Carotid Stenting: Results of the Randomized ARMYDA-9 CAROTID (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting) Study

OBJECTIVES This study sought to evaluate whether a strategy with a 600-mg clopidogrel load and a short-term, high-dose atorvastatin reload would improve outcomes in clopidogrel-naïve, statin-treated patients undergoing protected carotid stenting. BACKGROUND Optimal clopidogrel loading dose during carotid stenting has not been investigated; in addition, statin neuroprotection in this setting has not been described. METHODS A total of 156 patients were randomized using a 2 × 2 factorial design to receive either a 600-mg (n = 78) or 300-mg (n = 78) clopidogrel load given 6 h before intervention and either a atorvastatin reload (n = 76; 80 mg + 40 mg initiating 12 h before the procedure) or no statin reload (n = 80). The primary endpoint was the 30-day incidence of transient ischemic attack/stroke or new ischemic lesions on cerebral diffusion-weighted magnetic resonance imaging performed at 24 to 48 h. RESULTS Occurrence of the primary outcome measure was significantly lower in the 600-mg clopidogrel arm (18% vs. 35.9% in the 300-mg group; p = 0.019) and in the atorvastatin reload arm (18.4% vs. 35.0% in the no statin reload group; p = 0.031). High-dose clopidogrel also significantly reduced the transient ischemic attack/stroke rate at 30 days (0% vs. 9%, p = 0.02, secondary endpoint), without an increase in bleeding risk. CONCLUSIONS In patients undergoing carotid stenting, a strategy using both a 600-mg clopidogrel load and a short-term reload with high-dose atorvastatin protects against early ischemic cerebral events. These results, obtained along with routine mechanical neuroprotection, provide new evidence of the optimization of drug therapy before percutaneous carotid intervention. (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting [ARMYDA-9 CAROTID]; NCT01572623).

Interleukin-1 Receptor Antagonist: A Sensitive Marker of Instability in Patients with Coronary Artery Disease

AbstractBackground: Increased plasma levels of acute phase reactants are correlated with acute coronary syndromes and increased risk of in-hospital events. Interleukin-1 receptor antagonist (IL-1Ra) modulates the activity of IL-1, a cytokine associated with inflammatory response; we have prospectively investigated whether detection of increased levels of IL-1Ra in patients may be useful in the characterization of coronary syndromes. Methods: Plasma levels of IL-1Ra were measured in 118 consecutive patients undergoing coronary angiography with a clinical diagnosis of recent unstable angina (N = 57), chronic stable angina (N = 49) or atypical chest pain (N = 12). Results: Angiography showed significant coronary disease in the first two groups and was normal in the latter group. Patients with unstable angina had significantly higher levels of IL-1Ra than stable patients [158 (110–224) vs 108 (95–154) pg/ml, P = 0.002] and individuals with chest pain and normal coronary angiogram [110 (97–123) pg/ml, P: = 0.038]. In contrast, while C-reactive protein levels were significantly higher in patients with stable and unstable angina vs those without coronary disease (0.29 vs 0.06 mg/dl, P: = 0.022), they did not discriminate between stable and unstable angina patients (0.22 vs 0.32 mg/dl, P: = 0.66). Conclusions: These results indicate that IL-1Ra may be a sensitive marker of clinical instability in patients with coronary artery disease.

Coronary stenting in patients with depressed left ventricular function: Acute and long‐term results in a selected population

Percutaneous coronary angioplasty (PTCA) in patients with depressed left ventricular ejection fraction (LVEF) is associated with increased acute and late mortality; in contrast to plain PTCA, results of stenting in these patients have not been characterized. To assess the current outcome of stenting in patients with LV dysfunction, results from 80 patients procedures were analyzed. Intervention for acute myocardial infarction (MI) was excluded; 21% of patients had unstable angina and 30% had a recent MI. Mean LVEF was 40 ± 9% (range, 25–45%). Multivessel revascularization was done in 25 patients (31%), with a total of 114 lesions treated. Prophylactic intra‐aortic balloon pump was used in only two patients. Angiographic and clinical success was achieved in 79/80 patients (99%). There were no in‐hospital deaths, one patient (1%) had a non‐Q‐wave MI, and no patients required emergency bypass surgery (CABG). All patients completed at least 6 months follow‐up (mean, 30 ± 14 months): 64 patients (80%) remained asymptomatic, 4 (5%) had acute MI, and 5 (6%) died. In‐stent restenosis occurred in five patients (6%); of these, three required repeat PTCA, three patients (4%) underwent subsequent elective CABG. Including patients with repeat intervention, 67 patients (84%) are clinically improved; actuarial event‐free survival was 87% at 56‐month follow‐up. Thus, stenting in patients with impaired LVEF is associated with excellent outcome and lower mortality than previously reported for balloon angioplasty alone. Whether coronary stenting may be a therapeutic strategy equivalent to surgery in selected patients needs to be investigated in prospective randomized trials. Cathet Cardiovasc Intervent 2003;59:429–433.