Role of lipoprotein (a) and LPA KIV2 repeat polymorphism in bicuspid aortic valve stenosis and calcification: a proof of concept study.

Hemodynamic valvular impairment is a frequent determinant of the natural history of bicuspid aortic valve (BAV). The role of elevated Lp(a) levels and LPA Kringle IV type 2 (KIV-2) size polymorphism in influencing aortic valve calcification and stenosis development in patients with tricuspid aortic valve was recognized. In this study, we investigate the association between Lp(a) and LPA KIV-2 repeat number, and the presence of calcification and stenosis in BAV patients. Sixty-nine patients [79.7% males; median age 45(30-53) yrs], consecutively referred to Center for Cardiovascular Diagnosis or Referral Center for Marfan syndrome or related disorders, AOU Careggi, from June to November 2014, were investigated. For each patient, clinical (ECG and echocardiography) and laboratory [Lp(a) (Immunoturbidimetric assay) and LPA KIV-2 repeat number (real-time PCR)] evaluation were performed. Patients were compared with 69 control subjects. No significant association between Lp(a) circulating levels and LPA KIV-2 repeat number and BAV was evidenced. Among BAV patients, significantly higher Lp(a) levels according to calcification degree were found [no calcifications:78(42-159) mg/L, mild/moderate: 134(69-189) mg/L; severe: 560(286-1511) mg/L, p = 0.008]. Conversely, lower LPA KIV-2 repeat numbers in subjects with more severe calcification degree were observed. Furthermore, higher Lp(a) levels in patients with aortic stenosis [214(67-501) mg/L vs 104(56-169) mg/L, p = 0.043] were also found. In conclusion, present data suggest the potential role for Lp(a) as a possible risk marker useful to stratify, among BAV patients, those with a higher chance to develop valvular calcifications and aortic stenosis.

Dual antiplatelet therapy tailored on platelet function test after coronary stent implantation: a real-world experience.

Patients' response to dual antiplatelet therapy (DAPT) is subject to variations and its monitoring allows to individualize this therapy. In this study, we evaluated if a strategy of tailored DAPT after platelet function testing could reduce high on-treatment platelet reactivity (HPR) and improve outcome of patients treated with stent implantation. In 257 patients undergoing percutaneous angioplasty, platelet function was measured by light transmittance aggregometry (LTA) using 10 µM/L adenosine-diphosphate (ADP) and 1 mM arachidonic acid (AA) as agonists. Patients with HPR by ADP (≥70%) were switched to double-dose clopidogrel, ticlopidine, prasugrel or ticagrelor; in patients with HPR by AA (≥20%) acetylsalicylic acid dose was increased if not contraindicated. Platelet function analysis was repeated 48 hours after therapy variation. At 20-month follow-up major adverse cardiovascular events (MACE) and bleedings were assessed. HPR was detected in 97/257 (37.7%) patients: 69/257 (26.8%) had HPR by ADP and 71/257 (27.6%) had HPR by AA. In patients with HPR by ADP or by AA, tailored DAPT determined a significant reduction in residual platelet reactivity. No significant difference in MACE or bleeding occurrence was documented in HPR patients treated with tailored DAPT vs. those without HPR. HPR patients treated with tailored DAPT had significant lower follow-up MACE and deaths vs. 139 HPR patients not switched, even after propensity score analysis. These results suggest that a DAPT tailored on platelet testing can improve antiplatelet response in HPR patients, possibly reducing their thrombotic events to a level similar to non-HPR patients, without increasing the risk of bleeding.

Should we improve the management of NSTEMI? Results from the population-based "acute myocardial infarction in Florence 2" (AMI-Florence 2) registry.

ST-segment and non-ST-segment elevation myocardial infarction (STEMI, NSTEMI) have opposite epidemiology, the latter being nowadays more common than the former. Consistently with these epidemiological trends, application of evidence-based clinical practice guidelines on the management of NSTEMI should be promoted. We compared clinical features, hospital management and prognosis of STEMI/NSTEMI in an unselected cohort of 1,496 prospectively enrolled patients (STEMI, 36.9 % and NSTEMI, 63.1 %), admitted in 1 year to one of the six hospitals in Florence health district (Italy). Vital status was assessed after 1 year. NSTEMI patients were older, more often female, and affected by cardiovascular and non-cardiovascular comorbidities. Percutaneous coronary intervention (PCI) was performed more often in STEMI (82 %) than in NSTEMI patients (48 %, p < 0.001). Aspirin, clopidogrel, statins, beta-blockers, and ACE-inhibitors were prescribed more frequently in STEMI. In-hospital mortality was significantly lower in NSTEMI than in STEMI (4.2 vs. 8.9 %, p < 0.001), even after adjusting for confounders in a multivariable logistic model (OR 0.27, 95 % CI 0.16-0.45). One-year mortality was similar in NSTEMI and STEMI patients in an unadjusted comparison (18.0 vs. 16.7 %, p = 0.51), but it was lower in NSTEMI patients in multivariable Cox analysis (HR 0.56, 95 % CI 0.42-0.75). PCI reduced the risk of 1-year mortality similarly in STEMI (HR 0.47, 95 % CI 0.28-0.79) and NSTEMI (HR 0.41, 95 % CI 0.28-0.60). PCI reduces mortality in both STEMI and NSTEMI, but it is underutilised in patients with NSTEMI. To improve overall prognosis of AMI, efforts should be made at improving the care of NSTEMI patients.