Natural History of Coronary Atherosclerosis in Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: The Role of Quantitative Flow Ratio.

BACKGROUND: The prognostic impact of functionally significant coronary artery disease, as assessed with quantitative flow ratio (QFR), in patients with severe aortic stenosis treated with transcatheter aortic valve replacement is unknown. METHODS: This is a retrospective study with blind analysis of angiographic data, enrolling consecutive patients with severe aortic stenosis treated with transcatheter aortic valve replacement at 4 Italian centers. None of the patients enrolled received pre-transcatheter aortic valve replacement or concomitant coronary revascularization, either for the absence of significant coronary stenoses or by clinical decision. Visual estimation of diameter stenosis and QFR analysis were performed in all coronary arteries. The end point was all-cause mortality at a 3-year follow-up. RESULTS: A total of 318 patients were enrolled. At visual estimation, 140 patients (44%) presented a diameter stenosis ≥50% in at least 1 coronary artery, whereas 78 patients (24.5%) had at least 1 vessel with QFR <0.80 and, therefore, included in the positive QFR group. Overall, 69 (21.7%) patients died during the follow-up. In the Kaplan-Meier analysis, patients with positive QFR experienced significantly higher rates of death during follow-up compared with those without (51.1% versus 12.1%; P<0.001), whereas no significant difference was evident in terms of death between patients with or without significant coronary artery disease according to angiographic evaluation (24.3% versus 19.7%; P=0.244). In a multivariate regression model, positive QFR was an independent predictor of all-cause death during follow-up (hazard ratio, 5.31 [95% CI, 3.21-8.76]). CONCLUSIONS: Coronary QFR can predict mortality in patients with severe aortic stenosis treated with transcatheter aortic valve replacement without revascularization.

Periprocedural myocardial infarction after percutaneous coronary intervention and long-term mortality: a meta-analysis.

BACKGROUND AND AIMS: Conflicting data are available regarding the association between periprocedural myocardial infarction (PMI) and mortality following percutaneous coronary intervention. The purpose of this study was to evaluate the incidence and prognostic implication of PMI according to the Universal Definition of Myocardial Infarction (UDMI), the Academic Research Consortium (ARC)-2 definition, and the Society for Cardiovascular Angiography and Interventions (SCAI) definition. METHODS: Studies reporting adjusted effect estimates were systematically searched. The primary outcome was all-cause death, while cardiac death was included as a secondary outcome. Studies defining PMI according to biomarker elevation without further evidence of myocardial ischaemia ('ancillary criteria') were included and reported as 'definition-like'. Data were pooled in a random-effect model. RESULTS: A total of 19 studies and 109 568 patients were included. The incidence of PMI was progressively lower across the UDMI, ARC-2, and SCAI definitions. All PMI definitions were independently associated with all-cause mortality [UDMI: hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.32-1.97; I2 34%; ARC-2: HR 2.07, 95% CI 1.40-3.08, I2 0%; SCAI: HR 3.24, 95% CI 2.36-4.44, I2 78%]. Including ancillary criteria in the PMI definitions were associated with an increased prognostic performance in the UDMI but not in the SCAI definition. Data were consistent after evaluation of major sources of heterogeneity. CONCLUSIONS: All currently available international definitions of PMI are associated with an increased risk of all-cause death after percutaneous coronary intervention. The magnitude of this latter association varies according to the sensitivity and prognostic relevance of each definition.

Coronary Chronic Total Occlusion Revascularization: When, Who and How?

Coronary chronic total occlusions (CTO) are an increasingly frequent entity in clinical practice and represent a challenging percutaneous coronary intervention (PCI) scenario. Despite data from randomized trials that have not yet demonstrated a clear benefit of CTO recanalization, the widespread of CTO-PCI has substantially increased. The improvement in operators' techniques, equipment, and training programs has led to an improvement in the success rate and safety of these procedures, which will represent an important field of future development of PCI. The present review will summarize clinical outcomes and technical and safety issues of CTO revascularization with the aim to guide clinical daily cath-lab practice.

Systematic review and meta-analysis of randomized and nonrandomized studies on fractional flow reserve-guided revascularization.

INTRODUCTION AND OBJECTIVES: Several studies have investigated the effectiveness of fractional flow reserve (FFR) guidance in improving clinical outcomes after myocardial revascularization, yielding conflicting results. The aim of this study was to compare clinical outcomes in patients with coronary artery disease following FFR-guided or angiography-guided revascularization. METHODS: Both randomized controlled trials (RCTs) and nonrandomized intervention studies were included. Coprimary endpoints were all-cause death, myocardial infarction, and major adverse cardiovascular events (MACE). The study is registered with PROSPERO (CRD42022344765). RESULTS: A total of 30 studies enrolling 393 588 patients were included. FFR-guided revascularization was associated with significantly lower rates of all-cause death (OR, 0.63; 95%CI, 0.53-0.73), myocardial infarction (OR, 0.70; 95%CI, 0.59-0.84), and MACE (OR, 0.77; 95%CI, 0.70-0.85). When only RCTs were considered, no significant difference between the 2 strategies was observed for any endpoints. However, the use of FFR was associated with reduced rates of revascularizations and treated lesions. Metaregression suggested that the higher the rate of revascularized patients the lower the benefit of FFR guidance on MACE reduction compared with angiography guidance (P=.012). Similarly, higher rates of patients with acute coronary syndromes were associated with a lower benefit of FFR-guided revascularization (P=.039). CONCLUSIONS: FFR-guided revascularization was associated with lower rates of all-cause death, myocardial infarction and MACE compared with angiographic guidance, with RCTs and nonrandomized intervention studies yielding conflicting data. The benefits of FFR-guidance seem to be less evident in studies with high revascularization rates and with a high prevalence of patients with acute coronary syndrome.

Takotsubo Syndrome and Coronary Artery Disease: Which Came First-The Chicken or the Egg?

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.

Leptin as predictor of cardiovascular events and high platelet reactivity in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Leptin is a hormone involved in the regulation of food intake. Previous studies suggested an interplay between leptin, platelet aggregation, and cardiovascular outcome but this issue was not investigated in vivo in patients treated with percutaneous coronary intervention (PCI). We designed a study to evaluate the possible relation between leptin, cardiovascular outcome, and platelet reactivity (PR) in patients undergoing PCI. METHODS: 155 PCI patients had preprocedural measurements of PR and leptin plasma levels. The latter were assessed by ELISA. Hyperleptinemia was defined as leptin levels ≥14 ng/ml. PR was evaluated by the VerifyNowP2Y12 assay and expressed as P2Y12 reaction units (PRU). Patients were divided into three groups based on PR values and defined as low (LPR), normal (NPR), and high (HPR). Patients were followed for up 8 years. The primary endpoint was the incidence of Major Acute Cardiac Events (MACE) at long-term follow-up according to leptin groups. Secondary endpoints were the evaluation of leptin levels according to PR groups and the incidence of periprocedural myocardial infarction (PMI) according to leptin groups. RESULTS: Long-term follow-up was completed in 140 patients. Patients with hyperleptinemia experienced a higher MACE rate than the normoleptinemic group (HR 2.3; CI 95% 1.14-4.6, P = 0.02). These results remained unchanged after adjusting for Body Mass Index, hypertension, and gender. Leptin levels were significantly different among groups of PR (P = 0.047). Leptin levels were higher in the HPR group (12.61 ± 16.58 ng/ml) compared to the LPR group (7.83 ± 8.87 ng/ml, P = 0.044) and NPR group (7.04 ± 7.03 ng/ml, P = 0.01). The rate of PMI was higher in hyperleptinemia patients (15.1% vs. 6.5%, P = 0.22). CONCLUSIONS: This study suggests that high leptin levels are associated with a worse clinical outcome in patients undergoing PCI and with HPR. Further studies are needed to define better the pathophysiological pathways underlying this association.

Mid-Regional Pro-Adrenomedullin and N-Terminal Pro-B-Type Natriuretic Peptide Measurement: A Multimarker Approach to Diagnosis and Prognosis in Acute Heart Failure.

BACKGROUND: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. AIM AND METHODS: The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. RESULTS: Levels of MR-proADM (median: 2.07; (25th-75th percentiles: 1.40-3.02) vs. 1.11 (0.83-1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691-11,874) vs. 271 (89-931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13-7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42-30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05-9.91; p = 0.041). CONCLUSION: The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy.

Incretins-Based Therapies and Their Cardiovascular Effects: New Game-Changers for the Management of Patients with Diabetes and Cardiovascular Disease.

Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials (CVOT) reported the association between using these agents and a significant reduction in cardiovascular events in patients with T2D and a high cardiovascular risk profile. Moreover, recent evidence highlights a favorable benefit/risk profile in myocardial infarction and percutaneous coronary revascularization settings. These clinical effects result from their actions on multiple molecular mechanisms involving the immune system, platelets, and endothelial and vascular smooth muscle cells. This comprehensive review specifically concentrates on these cellular and molecular processes mediating the cardiovascular effects of incretins-like molecules, aiming to improve clinicians' knowledge and stimulate a more extensive use of these drugs in clinical practice as helpful cardiovascular preventive strategies.

Effects of ticagrelor and prasugrel on coronary microcirculation in elective percutaneous coronary intervention.

OBJECTIVE: To compare the effects of ticagrelor and prasugrel on absolute coronary blood flow (Q) and microvascular resistance (R) in patients with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI) (NCT05643586). Besides being at least as effective as prasugrel in inhibiting platelet aggregation, ticagrelor has been shown to have additional properties potentially affecting coronary microcirculation. METHODS: We randomly assigned 50 patients to ticagrelor (180 mg) or prasugrel (60 mg) at least 12 hours before intervention. Continuous thermodilution was used to measure Q and R before and after PCI. Platelet reactivity was measured before PCI. Troponin I was measured before, 8 and 24 hours after PCI. RESULTS: At baseline, fractional flow reserve, Q and R were similar in two study groups. Patients in the ticagrelor group showed higher post-PCI Q (242±49 vs 205±53 mL/min, p=0.015) and lower R values (311 (263, 366) vs 362 (319, 382) mm Hg/L/min, p=0.032). Platelet reactivity showed a negative correlation with periprocedural variation of Q values (r=-0.582, p<0.001) and a positive correlation with periprocedural variation of R values (r=0.645, p<0.001). The periprocedural increase in high-sensitivity troponin I was significantly lower in the ticagrelor compared with the prasugrel group (5 (4, 9) ng/mL vs 14 (10, 24) ng/mL, p<0.001). CONCLUSIONS: In patients with stable CAD undergoing PCI, pretreatment with a loading dose of ticagrelor compared with prasugrel improves post-procedural coronary flow and microvascular function and seems to reduce the related myocardial injury.

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned?

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.

Impact of Endothelial Dysfunction on Long-Term Clinical Outcomes in Patients With Chronic Coronary Syndromes Treated With Second Generation Drug-Eluting Stent Implantation.

BACKGROUND: Studies investigating clinical outcomes of patients with or without endothelial disfunction (ED) treated with percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) using second generation drug eluting stents (DES) are lacking. METHODS: We prospectively collected data from 109 patients undergoing PCI with second generation DES due to stable CAD between December 2014 and September 2016. ED was evaluated evaluating the flow mediated dilation (FMD) at the brachial artery level and defined by an FMD < 7 %. Primary outcome were major adverse cardiovascular events (MACE), secondary outcomes were target vessel failure (TVR), myocardial infarction (MI) and all-cause death. RESULTS: Five-year follow-up was available in all patients. Median FMD didn't significantly differ between patients who experienced the outcome and those who didn't [no TVR vs. TVR: p = 0.358; no MI vs. MI: p = 0.157; no death vs. death: p = 0.355; no MACE vs. MACE: p = 0.805]. No association between ED and an increased risk for the primary outcome as well as for the secondary ones was evident [MACE: 17.0 % vs. 14.3 %, HR 0.87 (0.33-2.26), log rank p = 0.780; TVR: 9.4 % vs. 5.4 %, HR 0.53 (0.12-2.24), log rank p = 0.384; MI: 3.7 % vs. 8.9 %, HR 2.46 (0.47-12.76), log rank p = 0.265; death: 7.5 % vs. 3.6 %, HR 0.53 (0.09-2.90), log rank p = 0.458]. These findings were confirmed using a lower threshold of FMD to define ED and at one-year landmark analysis. CONCLUSIONS: ED is not associated with an increased risk of adverse events at long-term follow-up in a contemporary cohort of patients undergoing PCI with second generation DES.

Relationship Between the Completeness of Revascularization and Myocardial Injury in Patients Treated With Percutaneous Coronary Intervention.

BACKGROUND: Clinical outcomes of patients suffering periprocedural myocardial injury and undergoing incomplete revascularization (IR) following percutaneous coronary intervention (PCI) has never been investigated. OBJECTIVE: To investigate the relationship between different thresholds of post-PCI cardiac troponin (cTn) elevation and revascularization completeness in determining long-term clinical outcomes. METHODS: Patients were stratified in tertiles according to preprocedural SYNTAX score (SS) (low: 0-6; medium: >6-11; high: >11) and residual SS (low: 0-4; medium: >4-8; high: >8). IR was defined by a rSS value >4. Three thresholds of myocardial injury were pre-specified: 5×, 35× and 70× 99th percentile upper reference limit (URL) increase of baseline cTn. Primary outcome was a composite of major adverse cardiac events (MACE) at two years of follow-up. RESULTS: 1061 patients undergoing PCI for stable coronary artery disease were enrolled. IR occurred in 249 (23.4 %) and major myocardial injury in 540 (50.9 %). Patients belonging to the highest tertile of SS showed an increased risk of experiencing IR and periprocedural myocardial injury. Two-year follow-up was available in 869. At multi-variate Cox's regression analysis, patients undergoing IR + cTn > 35 × URL and IR + cTn > 70 × URL showed an increased risk of MACE [HR 2.30 (1.19-4.41) and HR 3.20 (1.38-7.41); respectively]. CONCLUSIONS: Periprocedural myocardial injury is critically associated with MACE at two-year follow-up in patient treated with PCI who achieve IR. Despite conflicting evidence exists regarding the influence of periprocedural myocardial injury on clinical outcomes, patients undergoing IR seem to represent a high-risk subgroup.

Synergistic effect of myocardial injury and mid-regional proAdrenomedullin elevation in determining clinical outcomes of SARS-CoV-2 patients.

Objective: Coronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients. Materials and methods: All patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS). Results: A total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87-21.30; p < 0.001). Conclusion: The study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.

Fractional Flow Reserve-Guided Coronary Revascularization: Evidence from Randomized and Non-Randomized Studies.

Simple visual estimation of coronary angiography is limited by several factors that can hinder the proper classification of coronary lesions. Fractional flow reserve (FFR) is the most widely used tool to perform a physiological evaluation of coronary stenoses. Compared to isolated angiography, FFR has been demonstrated to be more effective in selecting those lesions associated with myocardial ischemia and, accordingly, impaired outcomes. At the same time, deferring coronary intervention in those lesions that do not show ischemic FFR values has proven safe and not associated with adverse events. Despite a major randomized clinical trial (RCT) and several non-randomized studies showing that FFR-guided revascularization could be superior to isolated angiography in improving clinical outcomes, subsequent RCTs have reported conflicting results. In this review, we summarize the principles behind FFR and the data currently available in the literature, highlighting the main differences between randomized and non-randomized studies that investigated this topic.

Absolute coronary flow and microvascular resistance reserve in patients with severe aortic stenosis.

BACKGROUND: Development of left ventricle (LV) hypertrophy in aortic stenosis (AS) is accompanied by adaptive coronary flow regulation. We aimed to assess absolute coronary flow, microvascular resistance, coronary flow reverse (CFR) and microvascular resistance reserve (MRR) in patients with and without AS. METHODS: Absolute coronary flow and microvascular resistance were measured by continuous thermodilution in 29 patients with AS and 29 controls, without AS, matched for age, gender, diabetes and functional severity of epicardial coronary lesions. Myocardial work, total myocardial mass and left anterior descending artery (LAD)-specific mass were quantified by echocardiography and cardiac-CT. RESULTS: Patients with AS presented a significantly positive LV remodelling with lower global longitudinal strain and global work efficacy compared with controls. Total LV myocardial mass and LAD-specific myocardial mass were significantly higher in patients with AS (p=0.001). Compared with matched controls, absolute resting flow in the LAD was significantly higher in the AS cohort (p=0.009), resulting into lower CFR and MRR in the AS cohort compared with controls (p<0.005 for both). No differences were found in hyperaemic flow and resting and hyperaemic resistances. Hyperaemic myocardial perfusion (calculated as the ratio between the absolute coronary flow subtended to the LAD, expressed in mL/min/g), but not resting, was significantly lower in the AS group (p=0.035). CONCLUSIONS: In patients with severe AS and non-obstructive coronary artery disease, with the progression of LV hypertrophy, the compensatory mechanism of increased resting flow maintains adequate perfusion at rest, but not during hyperaemia. As a consequence, both CFR and MRR are significantly impaired.

Glycaemic Control in Patients Undergoing Percutaneous Coronary Intervention: What Is the Role for the Novel Antidiabetic Agents? A Comprehensive Review of Basic Science and Clinical Data.

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and revascularization through percutaneous coronary interventions (PCI) significantly improves survival. In this setting, poor glycaemic control, regardless of diabetes, has been associated with increased incidence of peri-procedural and long-term complications and worse prognosis. Novel antidiabetic agents have represented a paradigm shift in managing patients with diabetes and cardiovascular diseases. However, limited data are reported so far in patients undergoing coronary stenting. This review intends to provide an overview of the biological mechanisms underlying hyperglycaemia-induced vascular damage and the contrasting actions of new antidiabetic drugs. We summarize existing evidence on the effects of these drugs in the setting of PCI, addressing pre-clinical and clinical studies and drug-drug interactions with antiplatelet agents, thus highlighting new opportunities for optimal long-term management of these patients.

Contrast-induced Acute Kidney Injury in Diabetic Patients and SGLT-2 Inhibitors: A Preventive Opportunity or Promoting Element?

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients undergoing diagnostic or therapeutic procedures that require contrast use and negatively affects the long-term outcomes. Patients with type 2 diabetes mellitus (DM), particularly those who have already developed diabetic nephropathy (DN), are more susceptible to contrast-induced renal damage. Indeed, contrast media amplify some pathological molecular and cellular pathways already in place in the DN setting. In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have triggered a paradigm shift in managing patients with type 2 DM, reducing cardiovascular and renal adverse events, and slowing DN development. Some evidence also suggests favorable effects of SGLT2i on acute kidney injury despite the initial alarm; however, little data exist regarding CI-AKI. The present review provides an updated overview of the most recent experimental and clinical studies investigating the beneficial effects of SGLT2i on chronic and acute renal injury, focusing on their potential role in the development of CI-AKI. Thus, we aimed to expand the clinicians' understanding by underscoring new opportunities to prevent this complication in the setting of DM, where effective preventive strategies are still lacking.

Circadian variations of platelet reactivity on clopidogrel in patients treated with elective percutaneous coronary intervention.

Evidence assessing potential diurnal variations of platelet reactivity in patients on clopidogrel treated with elective percutaneous coronary intervention (PCI) for chronic coronary syndrome (CCS) are currently lacking. We prospectively enrolled 15 patients affected by stable coronary artery disease (CAD) previously treated with elective PCI and on clopidogrel for at least 8 days (administered at 8 a.m.). A significant heterogeneity in diurnal levels of ADP-dependent platelet aggregation was found (p = 0.0004), with a peak of platelet reactivity occurring at the 6 a.m. assessment, which resulted significantly increased compared to the afternoon (6 p.m.) evaluation (255 ± 66 vs 184 ± 67, p = 0.002). In addition, at the early-morning evaluation a considerably high proportion of patients with high platelet reactivity (53.3%) were observed. In conclusion, clopidogrel-induced platelet inhibition in patients with CCS after elective PCI follows a circadian rhythm, thus suggesting that a consistent and durable antiplatelet inhibition is often failed with standard clopidogrel administration at morning.

Association Between Platelet Reactivity and Long-Term Bleeding Complications After Percutaneous Coronary Intervention According to Diabetes Status.

The relation between diabetes mellitus (DM) and bleeding complications after percutaneous coronary intervention (PCI) is controversial. This study investigates the role of low platelet reactivity (LPR) in the bleeding risk stratification of patients who underwent PCI according to DM status. A total of 472 patients who underwent PCI on aspirin and clopidogrel were included retrospectively. Platelet reactivity was assessed using the VerifyNow P2Y(12) assay. LPR was defined as platelet reactivity unit ≤178. The primary end point was the occurrence of any bleeding at 5 years stratified by DM status and LPR. DM was present in 30.5% of patients. LPR was less frequent in patients with DM (p = 0.077). Overall, 11.9% of patients experienced a bleeding complication at 5 years. The incidence of bleeding did not differ in subjects with and without DM (p = 0.24). LPR had a similar value for stratifying the increased bleeding risk in patients with and without DM (interaction p between DM and LPR 0.69). A stepwise increase in the crude rates of bleeding complications was observed across patients with and without LPR and DM (log-rank p = 0.004), with those affected by both conditions having the highest crude incidence rate. In conclusion, on top of aspirin, approximately 1/3 of patients who underwent PCI on clopidogrel have LPR. Assessment of LPR provides a significant incremental value for predicting bleeding irrespective of DM status. Although the presence of DM per se does not increase the incidence of hemorrhagic complications, the coexistence of DM and LPR identifies the subgroup with the highest bleeding risk.