Antonio Mafrici

One-year mortality in elderly adults with non-st-elevation acute coronary syndrome: Effect of diabetic status and admission hyperglycemia

To determine whether type 2 diabetes mellitus and hyperglycemia on admission should be considered independent predictors of mortality in elderly adults with acute coronary syndrome (ACS).

Role of Non-Transferrin-Bound Iron in the pathogenesis of cardiotoxicity in patients with ST-elevation myocardial infarction assessed by Cardiac Magnetic Resonance Imaging

BACKGROUND Hereditary hemochromatosis, thalassemia and myelodysplastic syndromes represent disease models with evidence of iron-related heart failure. Non-Transferrin Bound Iron (NTBI) induces cardiac toxicity through the production of reactive oxygen species and lipid peroxidation. In ST-elevation acute myocardial infarction (STEMI) with evidence of microvascular obstruction (MVO) and hemorrhage (HEM), HEM may be a source of iron-related cardiac toxicity through NTBI and pro-inflammatory mediators. AIM OF THE STUDY The study aims to assess NTBI in patients with STEMI and its possible relationship with MVO and HEM. METHODS AND RESULTS NTBI, LPO-Malondialdehyde (MDA) and interleukin-6 (IL-6) were assessed in 15 patients with STEMI immediately before primary percutaneous coronary intervention (PPCI) and at 3, 6, 9, 12, and 24h post-PPCI. Cardiac Magnetic Resonance (CMR) was performed at 5days and 6months after STEMI. Myocardial edema and HEM were assessed by T2 and T2* mapping. MVO and necrotic area were assessed by early and late gadolinium enhancement (LGE). NTBI was detected in 13/15 patients with the highest values in 4 patients with evidence of MVO and HEM. NTBI levels were significantly related to CK-MB and troponin T values. NTBI kinetics appeared to be different in patients with MVO and HEM (7/15 patients), with a peak value at 6h after PCI, in comparison with those with no evidence of MVO and HEM, in whom NTBI values were lower and remained indeterminable after the first 24h. CONCLUSIONS The detection of elevated NTBI values in patients with STEMI, MVO and HEM suggests a possible role of iron cardiotoxicity in myocardial damage.

Prasugrel and ticagrelor: is there a winner?

Clopidogrel is a prodrug that undergoes extensive enteric clearance and requires two-stage hepatic activation by cytochrome P450 (CYP) enzymes. This metabolic pathway is susceptible to genetic polymorphisms, resulting in a variable platelet inhibitory effect. A growing number of studies have linked poor antiplatelet response to clopidogrel to adverse clinical outcomes, particularly coronary ischemic events and stent thrombosis. This has prompted the development of new ADP receptor antagonists that inhibit platelets more effectively. Two of these agents, prasugrel and ticagrelor, have been investigated in two large randomized clinical trials, and both have shown superiority versus clopidogrel in reducing ischemic endpoints, with an increase in bleeding events, but a favorable final net clinical outcome. Since the publication of the main articles, several sub-analyses have been performed on the same data, and Guideline recommendations have largely endorsed these subgroup findings. Most clinicians have accepted the concept that we might consider approaching the patient differently, deserving a specific agent for each different settings. However, subgroup analyses of randomized trials are often post hoc, underpowered and prone to bias. Weighing efficacy and safety of the most commonly used antiplatelet agents will represent a clinical challenge over the next few years. Furthermore, individuals and organizations involved in formulary decisions will have to face economic constraints, also taking into account the availability of low-cost generic clopidogrel. In the following review, we have performed a critical appraisal of the current literature in order to outline lights and shadows on the most relevant clinical scenarios.

Management of diabetic patients hospitalized for acute coronary syndromes: a prospective multicenter registry

Background Patients with diabetes mellitus and acute coronary syndrome (ACS) present an increased risk of adverse cardiovascular events. An Italian Consensus Document indicated ‘three specific must’ to obtain in this subgroup of patients: optimal oral antiplatelet therapy, early invasive approach and a tailored strategy of revascularization for unstable angina/non-ST-elevation-myocardial infarction (UA/NSTEMI); furthermore, glycemia at admission should be managed with dedicated protocols. Aim To investigate if previous recommendations are followed, the present multicenter prospective observational registry was carried out in Lombardia during a 9-week period between March and May 2015. Methods and results A total of 559 consecutive ACS patients (mean age 68.7 ± 11.3 years, 35% ≥75 years, 50% STEMI), with ‘known DM’ (56%) or ‘hyperglycemia’, this last defined as blood glucose value ≥ 126 mg/dl at admission, were included in the registry at 29 hospitals with an on-site 24/7 catheterization laboratory. Patients with known diabetes mellitus received clopidogrel in 51% of the cases, whereas most patients with hyperglycemia (72%) received a new P2Y12 inhibitor: according to clinical presentation in case STEMI prasugrel/ticagrelor were more prescribed than clopidogrel (70 vs. 30%, P < 0.001); on the contrary, no significant difference was found in case of UA/NSTEMI (48 vs. 52%, P = 0.57). Overall, 96% of the patients underwent coronary angiography and 85% received a myocardial revascularization (with percutaneous coronary intervention in 92% of cases) that was however performed in fewer patients with known diabetes mellitus compared with hyperglycemia (79 vs. 90%, P = 0.001). Among UA/NSTEMI, 85% of patients received an initial invasive approach, less than 72 h in 80% of the cases (51% <24 h); no difference was reported comparing known diabetes mellitus to hyperglycemia. Despite similar SYNTAX score, patients with known diabetes mellitus had a higher rate of Heart Team discussion (29 vs. 12%, P = 0.03) and received a surgical revascularization in numerically more cases. Most investigators (85%) followed a local protocol for glycemia management at admission, but insulin was used in fewer than half of the cases; diabetes consulting was performed in 25% of the patients and mainly in case of known diabetes mellitus. Conclusion Based on data of the present real world prospective registry, patients with ACS and known diabetes mellitus are treated with an early invasive approach in case of UA/NSTEMI and with a tailored revascularization strategy, but with clopidogrel in more cases; glycemia management is taken into account at admission.

Evidence of non-transferrin-bound iron in patients with ST-elevation myocardial infarction: relationship with microvascular obstruction and post-reperfusion myocardial hemorrhage

Background Hereditary hemochromatosis, thalassemia and myelodysplastic sindromes represent iron toxicity models with evidence of iron-related heart failure. Non-TransferrinBound Iron (NTBI), plays a key role in the pathogenesis of cardiac toxicity leading to the production of reactive oxygen species which increase lipid peroxidation (MDA). In acute myocardial infarction (MI) microvascular obstruction (MVO) and hemorrhage (HEM) are independent predictors of left ventricular (LV) remodelling. HEM may be a source of iron toxicity through NTBI and pro-inflammatory mediators (IL-6) , which can directly contribute to acute impairment of myocardial function and adverse LV remodelling. The aim of the study was to assess NTBI in a consecutive cohort of patients (pts) prospectively enrolled with ST-elevation MI (STEMI).and its relationship with MVO and HEM.

Variations of left atrial activation patterns in congestive heart failure.

We report about a case of a patient admitted to the Intensive Cardiac Care Unit for severe congestive heart failure which showed modification of P‐wave morphology and duration, correlated with the clinical evolution. In the case here described, we show that ECG analysis, specifically P wave, allow us to assess the hemodynamic evolution of the acute decompensated heart failure patient.