Impact of age on pre-procedural TIMI flow in STEMI patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Advanced age is a major determinant of impaired prognosis among patients with ST-segment elevation myocardial infarction (STEMI). However, the mechanisms associated with suboptimal reperfusion and enhanced complications are still largely undefined. The aim of the present study was to assess the impact of age on the angiographic findings and the procedural results of primary percutaneous coronary intervention (pPCI) in patients with STEMI. METHODS: A consecutive cohort of patients admitted for STEMI treated with pPCI were included. Infarct-related artery (IRA) patency was defined for preprocedural TIMI flow 3. RESULTS: We included 520 patients, divided according to age tertiles (<61; 61-72; ≥73). Elderly patients were more often females, with hypertension, renal failure, prior myocardial infarction or PCI, with lower rates of smoking history, haemoglobin, leukocytes and cholesterol (P < 0.001), lower ejection fraction (P = 0.02), higher use of renin angiotensin system inhibitors, statins, ASA, calcium antagonists, diuretics and beta blockers. At angiography, for the IRA, percentage of thrombus (P = 0.02) and stenosis (P = 0.01), direct stenting (P = 0.02) and glycoprotein IIb-IIIa inhibitors (P = 0.04) inversely related with age, but for higher restenosis (P = 0.04). IRA patency was more common in patients aged ≥73 years (27.9% vs. 32.3% vs. 41.1%, P = 0.01). The impact of age on preprocedural TIMI flow was confirmed at multivariate analysis [adjusted odds ratio (95% confidence interval) = 0.68 (0.47-0.98), P = 0.04]. CONCLUSION: The present study shows that among STEMI patients undergoing primary PCI, more advanced age represents an independent predictor of preprocedural IRA patency. Future studies will define the implications on procedural results and long-term prognosis.

Impact of renal failure and high-platelet reactivity on major cardiovascular ischemic events among patients with acute coronary syndrome receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: No study has so far evaluated the impact of chronic kidney disease (CKD) on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were therefore the aim of the present study. METHODS: Patients on dual antiplatelet therapy with ASA+ticagrelor (90mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome (MI), target vessel revascularization) at the longest available follow-up. RESULTS: We included 396 patients, that were divided according to CKD (eGFR

Low hemoglobin predicts high-platelet reactivity and major cardiovascular ischemic events at long-term follow-up among ACS patients receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: Reduced levels of hemoglobin (Hb) represent an established marker of impaired outcomes and increased cardiovascular risk in patients with coronary artery disease, challenging the management of dual antiplatelet therapy (DAPT). However, while anemia has emerged as an independent predictor of suboptimal platelet inhibition in patients receiving clopidogrel, no study has so far evaluated the impact of Hb levels on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were the aim of the present study. METHODS: Patients on DAPT with ASA + Ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome [MI], target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients that were divided according to tertiles values of Hb (< 12.7, 12-7-14.09, ≥14.1 g/dl). Patients with lower Hb were older and displayed a more severe cardiovascular risk profile. Mean levels of platelet reactivity were enhanced in patients with lower Hb after stimulation with TRAP peptide (TRAP test, p = .03) and ADP (p = .02). Elevated platelet reactivity (HRPR) on Ticagrelor was more frequent among patients with reduced Hb (16.4% vs. 12% vs. 5.4%, p = .005, adjusted OR [95%CI] = 1.71[0.996;3.01], p = .056). At a mean follow-up of 820.9 ± 553.4 days, 21.4% of the patients experienced the primary composite endpoint, with a higher rate of events in patients with lower Hb (27.6% vs. 22.6% vs. 13.5%, p = .006, adjusted HR [95%CI] = 1.51[1.12; 2.03], p = .006), mainly driven by a higher rate of recurrent ACS. After correction for baseline differences lower Hb tertiles but not HRPR emerged as independent predictor of MACE (adjusted HR [95%CI] = 0.98[0.50; 1.92], p = .95). CONCLUSIONS: In the present study, we demonstrated that among patients on DAPT with ASA and ticagrelor after PCI for ACS, lower Hb levels are independently associated with a higher rate of HRPR and an increased rate of major ischemic events, and especially for recurrent ACS, although with no impact on survival. Neutral prognostic effect of HRPR was observed across Hb tertiles.

Impact of aging on the effects of intracoronary adenosine, peak hyperemia and its duration during fractional flow reserve assessment.

INTRODUCTION: Functional assessment of coronary stenoses is crucial for determining the correct therapeutic strategy. Age-related modifications in cardiovascular function could alter the functional significance of an intermediate coronary lesion. Therefore, the aim of the present study was to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease. METHODS: We included patients undergoing coronary angiography at our Division of Cardiology from June 2008 to February 2019 for elective indication or recent acute coronary syndrome and receiving FFR assessment for an intermediate coronary stenosis (angiographic 40-70% stenoses). FFR measurement was performed by pressure-recording guidewire (Prime Wire; Volcano Imaging System Philips Healthcare, San Diego, California, USA), after induction of hyperemia with intracoronary boluses of adenosine (from 60 to 720 µg, with dose doubling at each step). RESULTS: We included in our study 276 patients, undergoing FFR evaluation on 314 lesions, that were divided according to age (< or ≥70 years). Elderly patients displayed a higher cardiovascular risk profile and received more often specific therapy. We found significantly higher FFR values and lower Delta FFR and time to recovery in patients with age ≥70 years old even with high-dose adenosine. Elderly patients showed a trend in lower percentage of positive FFRs, especially with high-dose (P = 0.09). Overall, any FFR ≤ 0.80 was observed in 33.5% of younger patients and 21.1% of patients ≥70 years (P = 0.02). Results were confirmed after correction for baseline differences [adjusted odds ratio (95% confidence interval) = 0.60 (0.33-1.09), P = 0.08]. CONCLUSION: This is one of the first studies investigating the impact of age on the measurement of FFR with high-dose adenosine. Patients with age >70 years old with intermediate CAD are more likely to have higher FFR values and lower duration of hyperemia after adenosine boluses, as compared with younger patients.

Impact of Age on the Functional Evaluation of Intermediate Coronary Stenoses With Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

The optimal strategy for assessing the ischemic significance of intermediate coronary stenoses with adenosine-induced fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) is still debated. Few studies have previously assessed the impact of age on FFR and iFR, which was the aim of our study. Patients undergoing FFR and iFR evaluation for intermediate (40%-70%) coronary lesions were included and divided according to age. Fractional flow reserve was performed by intracoronary boluses of adenosine (60-1440 µg). Instantaneous wave-free ratio was automatically calculated. Among 148 patients undergoing FFR measurement of 166 lesions, 45.3% were ≥70 years. Elderly patients had higher minimal lumen diameter (P = .03). We also observed a linear relationship between iFR and FFR independently of age. Fractional flow reserve values were higher in the elderly patients, whereas iFR was not related to age. A total of 33 lesions had a positive iFR with no difference for age (17.3% vs 22%, P = .56), while FFR <0.80 was more infrequent in the elderly patients (17.1% vs 34.8%, P = .02). In intermediate coronary stenoses, iFR and FFR correlation is unaffected by age. Fractional flow reserve is higher in the elderly patients, whereas iFR is less affected by age. Future large-scale studies are needed to define whether iFR should be the preferred choice in elderly patients.

Association of lower vitamin D levels with inflammation and leucocytes parameters in patients with and without diabetes mellitus undergoing coronary angiography.

BACKGROUND: Diabetes mellitus has been associated with a chronic low-grade inflammation and a higher risk of cardiovascular and infectious disease, that could be prevented by the effects of vitamin D. We aimed at evaluating the impact of vitamin D levels on the biomarkers of acute-phase response, inflammation and glucose metabolism in a large cohort of diabetic patients with cardiovascular disease. MATERIALS AND METHODS: Consecutive patients undergoing coronary angiography were included. Diabetes mellitus was defined as previous diagnosis, specific treatment administration (oral drug or insulin), fasting glycaemia >6.99 mmol/L or HbA1c >48 mmol/L. Glucose parameters, white blood cells, Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), C-reactive protein (CRP) and vitamin D were measured at admission. Vitamin D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). RESULTS: We included 1472 diabetic patients and 2499 non-diabetic patients that were divided according to vitamin D tertiles. Among diabetic patients, lower levels of vitamin D were associated with female gender (P = .02), obesity (P = .004), active smoking and acute presentation (P < .001) and with a more atherogenic metabolic profile. The levels of white blood cells, leucocytes subfamilies, and inflammatory parameters significantly correlated with vitamin D levels in both patients with and without diabetes (diabetic: P = .012 for WBC, P = .004 for NLR and P < .001 for MLR and C-reactive protein, non-diabetic: P < .001 for WBC; NLR, MLR and C-reactive protein, respectively). Among diabetic patients, results were confirmed at multivariate analysis with no significant interaction according to glycaemic control. CONCLUSION: The present study demonstrates that, among patients with cardiovascular disease, vitamin D deficiency is associated with metabolic dysregulation and with an elevation of cellular and humoural inflammatory parameters, especially among diabetics, although not being dependent from glycaemic control.

Impact of the rs73598374 polymorphism of the adenosine deaminase gene on platelet reactivity and long-term outcomes among patients with acute coronary syndrome treated with ticagrelor.

BACKGROUND: The positive interaction of ticagrelor with the metabolism of adenosine has been claimed for the large antithrombotic and antiischemic benefits of this antiplatelet agent in acute coronary syndromes (ACS). Adenosine catabolism is regulated by the activity of the adenosine deaminase enzyme (ADA), for which several polymorphisms have been identified. Therefore, the aim of our study was to explore the impact of the rs73598374 polymorphism of ADA gene on platelet reactivity in ACS patients treated with ticagrelor. METHODS: We included consecutive patients receiving ASA and ticagrelor after an ACS and coronary intervention. Platelet reactivity was evaluated by impedance aggregometry at 30-90 days post-discharge. The genetic analysis was carried out by PCR and RFLP. Clinical endpoints were mortality, cardiovascular death, recurrent myocardial infarction or coronary revascularization at the maximum available follow-up. RESULTS: Our population is represented by 464 patients, of whom 33.4% were A-heterozygotes and 6 homozygotes. A-allele carriers showed a greater prevalence of renal failure (p = 0.02) and a lower rate of previous coronary artery bypass graft (p = 0.03) and statin treatment (p = 0.02). No differences in the mean values of platelet reactivity or HRPR on ticagrelor were found according to the ADA genotype (11.3%vs13.9%, p = 0.45; adjusted OR[95% CI] = 1.17[0.64-2.14], p = 0.61). At follow up, patients carrying the A-allele showed a non-significantly lower incidence of ACS and repeated unplanned revascularization, although with no effect on mortality. CONCLUSIONS: In the present study the rs73598374 polymorphism of the ADA gene did not affect platelet reactivity or the long-term prognosis in patients with ACS receiving dual antiplatelet therapy with ASA and ticagrelor.

Higher neutrophil-to-lymphocyte ratio (NLR) increases the risk of suboptimal platelet inhibition and major cardiovascular ischemic events among ACS patients receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has emerged as a useful and easy-to-assess prognostic tool and biomarker of cardiovascular risk. However, few studies have evaluated its role on platelet inhibition among patients on dual antiplatelet therapy (DAPT), and especially in the settings of acute coronary syndromes (ACS). We aimed at assessing the impact of NLR on platelet reactivity and the risk of major ischemic events at long-term follow-up among ACS patients on DAPT with ticagrelor. METHODS: Patients on dual antiplatelet therapy with ASA + ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by Multiple Electrode Aggregometry (MEA). Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome, target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients, that were divided according to NLR tertiles. Patients with higher NLR were older (p < .001), less frequently smokers (p = .03), with higher rates of renal failure (p = .001), previous bypass surgery (p = .05) and use of statins (p = .03) and diuretics (p = .01). Higher white blood cells count and C-reactive protein (p < .001) and lower haemoglobin (p = .001) were associated with NLR. Mean platelet reactivity and the prevalence of high platelet reactivity (HRPR) on ticagrelor were significantly associated to higher NLR tertiles values (7% vs 12% vs 14.3%, p = .04), with a significant relationship between NLR and platelet reactivity being confirmed for all the different activating stimuli. At a mean follow-up of 939 ± 581.4 days, 21.2% of the patients experienced the primary composite endpoint, with a trend for a higher risk of events across NLR tertiles (15.4% vs 24.2% vs 24.4%, p = .09), that became statistically significant after correction for baseline confounders (adjusted HR[95%CI] = 1.13[1.008-1.26], p = .036). Moreover, NLR was significantly associated to overall mortality and recurrent ACS (adjusted p = .008, p = .06 and p = .02 respectively). CONCLUSIONS: In the present study we found that among ACS patients treated with ASA and ticagrelor after PCI, suboptimal platelet inhibition despite DAPT was significantly increased for higher values of Neutrophil-to-Lymphocyte Ratio. Moreover, mortality and the risk of recurrent major ischemic events at long-term were associated to NLR.

Gender Differences in Platelet Reactivity in Diabetic Patients Receiving Dual Antiplatelet Therapy.

BACKGROUND: Increased comorbidities and a perceived high-bleeding risk often prevent the use of dual antiplatelet therapy (DAPT) in female patients. However, more aggressive antiplatelet treatment would certainly offer additional outcome benefits in coronary artery disease, especially among diabetic patients. The aim of the present study was to evaluate the gender differences in high-residual on treatment platelet reactivity (HRPR) among diabetic patients treated with DAPT. METHODS: Our population is represented by a consecutive cohort of diabetic patients treated with DAPT (ASA + clopidogrel, ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry and in diabetic patients naïve to antiplatelet therapy, by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2. RESULTS: We included 472 patients, 113 (23.9%) women. Female gender was associated with more advanced age, and increased comorbidities. Mean platelet reactivity did not differ according to gender. The rate of HRPR was similar in women as compared to men (for ASA: adjusted OR[95%CI] = 0.59[0.27-1.33], p = 0.21, for ADP-antagonists: adjusted OR[95%CI] = 1.24[0.25-1.80], p = 0.27), however, the benefits of the new ADP-antagonists on platelet reactivity were lower in women than in men (p interaction = 0.01). No impact of gender on platelet reactivity was confirmed among 50 diabetic patients naïve to antiplatelet therapy. CONCLUSIONS: Among diabetic patients receiving dual antiplatelet therapy gender does not affect platelet reactivity or high-on treatment platelet reactivity. However, the enhanced platelet inhibition provided by the new-ADP antagonists of new-ADP antagonists could be mitigated in women.

Incidental Diagnosis After a Car Accident: A Rare Case of Asymptomatic Uncorrected Tetralogy of Fallot.

Tetralogy of Fallot (TOF) is a heterogeneous congenital heart disease that is occasionally diagnosed during adulthood. However, although they are often asymptomatic, adult patients with uncorrected TOF often have a poor prognosis. Poor outcomes indicate the importance of the identification and management of these patients, especially in the context of intercurrent disease or noncardiac surgery. We describe a case of clinically silent TOF in a 51-year-old woman. TOF was unmasked during a major noncardiac surgery for a polytrauma and successfully treated with the cooperation of a multidisciplinary team. (Level of Difficulty: Advanced.).