Rationale and design of COLchicine On-admission to Reduce inflammation in Acute Coronary Syndrome (COLOR-ACS) study.

AIMS: The aim of the colchicine on-admission to reduce inflammation in acute coronary syndrome (COLOR-ACS) study is to evaluate the effects of the addition of short-term, low-dose colchicine to high-dose atorvastatin in limiting levels of inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: The COLOR-ACS study is a multicenter, randomized, open-label, two-arm trial. Statin-naive patients with NSTE-ACS, scheduled for an early invasive strategy, are randomized on admission to receive standard treatment of atorvastatin 80 mg or standard treatment plus colchicine (1 mg loading dose followed by 0.5 mg/day until discharge). The main exclusion criteria are prior statin and/or colchicine treatment, current treatment with potent inhibitors of CYP3A4, P-glycoprotein or immunosuppressive drugs, known active malignancy, severe kidney, cardiac, liver disease. There is clinical and biochemical follow-up at 30 days after discharge and telephone interview at 6 months. The primary end point is the change in hs-CRP from admission to discharge. Secondary end points include: incidence of acute kidney injury; MB fraction of creatine kinase peak value; glomerular filtration rate change from baseline to 30 days; persistence of hs-CRP ≥2 mg/dl at 30 days; adverse clinical events within 30 days; tolerance to colchicine. CONCLUSION: The COLOR-ACS study will provide evidence on the efficacy of early short-term treatment with colchicine in addition to high-dose atorvastatin compared to atorvastatin alone in ACS patients. The potential anti-inflammatory action of colchicine plus atorvastatin is expected to limit hs-CRP increase with resultant clinical benefits. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05250596.

Contrast-induced nephropathy in urgent coronary interventions.

OBJECTIVES: Patients submitted to urgent percutaneous coronary interventions (PCIs) are quite often at high risk for contrast-induced nephropathy (CIN) since they exhibit several predisposing factors such as electrical and haemodynamic instability together with the lack of time to undergo adequate prophylaxis. This was a not blinded, non-randomized study whose aims were (i) to evaluate the incidence of CIN after urgent PCI in a high-volume cardiovascular referral practice (patients with acute myocardial infarction or with acute coronary syndromes enrolled in a single centre), and (ii) to assess the prognostic implications of CIN during hospitalization and at 1-month follow-up. METHODS: Between 1 October 2003 and 1 April 2004, 194 consecutive patients undergoing urgent coronary angiography and PCIs at our catheterization laboratory were enrolled in the study: 67 patients (34.5%) received the iso-osmolar contrast medium iodixanol (group A) and 127 patients (65.5%) received the hypo-osmolar contrast medium iopromid (group B). RESULTS: The overall incidence of CIN was 10.82%. Patients of group A showed a higher incidence of CIN than patients of group B (22.3 vs. 4.7%, P < 0.05). On univariate logistic analysis, age, pre-existing renal insufficiency, intra-aortic balloon pump (an indirect indicator of haemodynamic instability), dyslipidaemia, and postprocedural hypotension were risk indicators for the development of CIN after primary PCI. On multivariate logistic analysis, age and postprocedural hypotension remained significant independent correlates of CIN. CONCLUSIONS: In emergency PCIs, CIN is a frequent complication mainly related to haemodynamic instability and pre-existing renal dysfunction. Since CIN is associated with a high in-hospital mortality rate, our data stress the need for the development and validation of new preventive strategies for renal protection during emergency PCIs.

The incidence and timing of major arrhythmias following successful primary angioplasty for acute myocardial infarction.

BACKGROUND: The potential benefits of direct percutaneous transluminal coronary angioplasty (PTCA) on malignant arrhythmias in the hospital phase of acute myocardial infarction have not yet been established. METHODS: We prospectively investigated the incidence and timing of major arrhythmias occurring during direct PTCA and within 24 hours of mechanical reperfusion in 90 consecutive patients with acute myocardial infarction undergoing successful direct PTCA within 12 hours of symptom onset. RESULTS: Ventricular fibrillation and complete atrioventricular block occurred exclusively during direct PTCA and both resolved in the catheterization laboratory. Holter monitoring showed that ventricular tachyarrhythmias, such as runs of more than 3 extrasystoles, were detectable only during the first 8 hours after direct PTCA. CONCLUSIONS: In our group of patients undergoing successful direct PTCA, no in-hospital life-threatening arrhythmias occurred after this procedure.

Low protein Z plasma levels are independently associated with acute coronary syndromes.

Protein Z (PZ) is a single chain vitamin-K-dependent glycoprotein synthesized by the liver. Studies in vivo and in vitro suggest that PZ plays an important role in inhibiting coagulation as it serves as cofactor for the inactivation of factor Xa by forming a complex with the plasma PZ-dependent protease inhibitor. Recently, conflicting findings on plasma PZ levels in patients with ischemic stroke have been published. Aim of our study was to investigate the role of PZ in acute coronary syndromes (ACS). PZ plasma levels were determined in 223 (189 M; 34 F) patients with ACS referring to the Coronary Intensive Therapy Unit of University of Florence and in 265 (219 M; 46 F) healthy subjects. Patients under oral anticoagulation treatment as well as subjects with positivity for antiphospholipid antibodies were excluded. None had liver or kidney dysfunction. The mean PZ plasma level was lower in patients (1508 +/- 730 ng/mL) than in controls (1728 +/- 594 ng/mL) (p < 0.0001). PZ levels below the 5th percentile (565 ng/mL) of normal values distribution in control subjects were found in 15.7% of patients and in 4.9% of controls (p <0.0001). At multivariate analysis, PZ levels below 565 ng/mL were associated with ACS (OR=3.3; 99%CI 1.1-9.7; p = 0.004). The contemporary presence of low PZ levels and smoking habit leads to an increased risk of ACS (OR=9.5; 99%CI 2.4-37.2; p < 0.0001). In conclusion, our results suggest a possible role of PZ in the occurrence of arterial thrombosis.

Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation.

AIM: The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF). METHODS AND RESULTS: Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300-450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers. CONCLUSION: A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.