Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate Coronary Artery Lesions.

BACKGROUND Progression of chronic coronary syndrome (CCS) is influenced by chronic kidney disease (CKD). This 5-year follow-up study aimed to assess 100 patients with 118 intermediate coronary artery lesions evaluated by fractional flow reserve (FFR) and intravascular imaging stratified according to renal function. MATERIAL AND METHODS This prospective study enrolled patients with intermediate coronary stenosis identified by coronary angiogram. Patients with severe renal dysfunction (estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m²) were excluded from the study. The remaining were divided into 2 groups according to eGFR: 45-60 ml/min/1.73 m² for mild-to-moderate renal dysfunction and >60 ml/min/1.73 m² for no renal dysfunction. We analyzed intermediate-grade stenoses (40-80% as assessed in coronary angiography) with the use of optical coherence tomography (OCT), FFR, and intravascular ultrasound (IVUS). RESULTS Renal dysfunction patients were older (67.7±8.1 vs 63.6±9.7 years, P=0.044). Lesion characteristics, including plaque type and minimal lumen area in OCT, showed no significant differences between the renal dysfunction and no renal dysfunction groups. Thin-cap fibroatheroma, calcific plaques, lipidic plaques, and fibrous plaques had similar prevalence. FFR values and IVUS parameters did not significantly differ between the groups. Over a 5-year follow-up, individuals with mild-to-moderate renal dysfunction had an elevated risk of all-cause mortality and major adverse cardiovascular events in multivariate analyses adjusted for age and sex. CONCLUSIONS Mild-to-moderate renal dysfunction was not associated with significant differences in OCT- and IVUS-derived plaque morphology nor with functional indices characterizing intermediate-grade coronary stenoses. Renal dysfunction was related to a higher risk of all-cause mortality and major adverse cardiovascular events prevalence in 5-year follow-up.

Prognostic Implications of Immature Platelet Fraction at 5-Year Follow-up Among ACS Patients Treated With Dual Antiplatelet Therapy.

Objective: Platelets are strongly associated with cardiovascular events due to their role in thrombotic processes. Reticulated platelets have higher prothrombotic potential. The aim of the study was to evaluate the effectiveness of immature platelet fraction (IPF) in predicting long-term clinical outcomes in patients with acute coronary syndrome (ACS). Methods: This prospective, observational study enrolled patients with ACS treated with dual antiplatelet therapy comprising acetylsalicylic acid and clopidogrel or ticagrelor. The primary outcome was a composite endpoint defined as major adverse cardiovascular events (MACE): all-cause death, myocardial infarction (MI), ischemic stroke, or unplanned revascularization. IPF was determined using flow cytometry in the first 24 h of hospitalization. MACE were evaluated by 2 physicians based on electronic databases and source documentation including discharge letters received from patients upon telephone contact. Results: Overall, there were 140 ACS patients (mean age 65.1 ± 11.7, 37 females [26.4%]) included in this study. Of them, 22.9% had diabetes mellitus, 69.3% hyperlipidemia, 25% had a history of MI. The median IPF values were 2.85 [1.8-4.2] %. Clinical follow-up (median time: 57 months [interquartile range 55-59 months]) was available for 130 patients (92.9%). MACE occurred in 27 patients (20.8%). There were higher rates of MACE at higher IPF tertiles (3rd vs 1st tertile: HR = 5.341 95% CI: 1.546-18.454, P = .008). Cox regression analyses showed that IPF level was independently associated with MACE. Time-dependent receiver-operating characteristic curve analysis revealed area under the curve of 0.656 for 5-year outcome with an IPF cutoff point of 3.45% being 63.0% sensitive and 65.0% specific for MACE. Conclusions: The study showed IPF may be an independent predictor of long-term mortality and MACE (ClinicalTrials.gov number, NCT06177587).

Long COVID and its cardiovascular consequences: What is known?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems. This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

Immature platelet fraction and immature platelet count as novel biomarkers of elevated platelet reactivity in NSTE-ACS patients receiving dual antiplatelet therapy.

BACKGROUND: Antiplatelet therapy is the cornerstone of treatment for patients presenting with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Some patients may not respond to such therapy adequately, which is associated with a greater risk of ischemic events. Reticulated platelets are the youngest, largest, and most active platelet subtype. They have been initially shown to be associated with an increased risk of cardiovascular (CV) events and increased platelet activity. OBJECTIVES: The aim of the presented study was to evaluate whether the immature platelet fraction (IPF) reflects the response to antiplatelet treatment in invasively managed ACS patients. MATERIAL AND METHODS: This prospective study enrolled ACS patients treated with PCI and dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid (ASA) and clopidogrel or ticagrelor. In all patients, venous blood was collected within 24 h after the procedure. Platelet parameters were measured, including IPF using the Sysmex hematological analyzer and adenosine diphosphate (ADP)-induced platelet reactivity using the Multiplate® Analyzer. RESULTS: A total of 108 patients were enrolled, including 62 with ST-segment elevation ACS (STE-ACS) and 46 with non-ST-segment elevation ACS (NSTE-ACS). Of them, 20.4% had diabetes mellitus, 26.9% had a history of MI and 59.2% of smoking. Spearman's correlation analysis demonstrated that higher IPF and immature platelet count (IPC) values are associated with increased ADP-induced platelet reactivity (respectively: rho = 0.387, 95% confidence interval (95% CI): 0.101-0.615, p = 0.008; and rho = 0.458, 95% CI: 0.185-0.666, p = 0.001) in NSTE-ACS but not in STE-ACS patients. CONCLUSION: Immature platelet count and IPF may be valuable markers of platelet activity in patients with NSTE-ACS treated invasively and receiving DAPT (ClinicalTrials.gov No. NCT06177587).

Multimodality OCT, IVUS and FFR evaluation of coronary intermediate grade lesions in women vs. men.

Background: The pathophysiology of atherosclerotic plaque formation and its vulnerability seem to differ between genders due to contrasting risk profiles and sex hormones, however this process is still insufficiently understood. The aim of the study was to compare the differences between sexes regarding the optical coherence tomography (OCT), intravascular ultrasound (IVUS) and fractional flow reserve (FFR)-derived coronary plaque indices. Methods: In this single-center multimodality imaging study patients with intermediate grade coronary stenoses identified in coronary angiogram (CAG) were evaluated using OCT, IVUS and FFR. Stenoses were considered significant when the FFR value was ≤0.8. Minimal lumen area (MLA), was analyzed by OCT in addition to plaque stratification into fibrotic, calcific, lipidic and thin-cap fibroatheroma (TCFA). IVUS was used for evaluation of lumen-, plaque- and vessel volume, as well as plaque burden. Results: A total of 112 patients (88 men and 24 women) with chronic coronary syndromes (CCS), who underwent CAG were enrolled. No significant differences in baseline characteristics were present between the study groups. The mean FFR was 0.76 (0.73-0.86) in women and 0.78 ± 0.12 in men (p = 0.695). OCT evaluation showed a higher prevalence of calcific plaques among women than men p = 0.002 whereas lipid plaques were more frequent in men (p = 0.04). No significant differences regarding minimal lumen diameter and minimal lumen area were found between the sexes. In IVUS analysis women presented with significantly smaller vessel area, plaque area, plaque volume, vessel volume (11.1 ± 3.3 mm2 vs. 15.0 ± 4.6 mm2 p = 0.001, 6.04 ± 1.7 mm2 vs. 9.24 ± 2.89 mm2 p < 0.001, 59.8 ± 35.2 mm3 vs. 96.3 (52.5-159.1) mm3 p = 0.005, 106.9 ± 59.8 mm3 vs. 153.3 (103-253.4) mm3 p = 0.015 respectively). At MLA site plaque burden was significantly greater for men than women (61.50 ± 7.7% vs. 55.5 ± 8.0% p = 0.005). Survival did not differ significantly between women and men (94.6 ± 41.9 months and 103.51 ± 36.7 months respectively; p = 0.187). Conclusion: The presented study did not demonstrate significant differences in FFR values between women and men, yet a higher prevalence of calcific plaques by OCT and lower plaque burden at the MLA site by IVUS was found in women vs. men.

Intravascular Imaging versus Physiological Assessment versus Biomechanics-Which Is a Better Guide for Coronary Revascularization.

Today, coronary artery disease (CAD) continues to be a prominent cause of death worldwide. A reliable assessment of coronary stenosis represents a prerequisite for the appropriate management of CAD. Nevertheless, there are still major challenges pertaining to some limitations of current imaging and functional diagnostic modalities. The present review summarizes the current data on invasive functional and intracoronary imaging assessment using optical coherence tomography (OCT), and intravascular ultrasound (IVUS). Amongst the functional parameters-on top of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR)-we point to novel angiography-based measures such as quantitative flow ratio (QFR), vessel fractional flow reserve (vFFR), angiography-derived fractional flow reserve (FFRangio), and computed tomography-derived flow fractional reserve (FFR-CT), as well as hybrid approaches focusing on optical flow ratio (OFR), computational fluid dynamics and attempts to quantify the forces exaggerated by blood on the coronary plaque and vessel wall.

Immature platelet fraction in cardiovascular diagnostics and antiplatelet therapy monitoring.

Immature platelet fraction (IPF), circulating platelets still containing RNA, can be easily calculated by automated flow cytometry, this makes them an accessible biomarker. Higher IPF concentrations were reported in patients with thrombocytopenia, patients who were smokers, and also those who were diabetics. Several studies have reported their diagnostic and prognostic importance in patients presenting with acute coronary syndromes, especially ST-segment elevation myocardial infarction, where increased IPF level is an independent predictor of cardiovascular death. In addition, higher IPF were reported in patients with inadequate response to either clopidogrel or prasugrel, suggesting their potential role in antiplatelet therapy monitoring. Their prognostic significance was also observed in both coronary artery disease and postcardiac surgery status, where their higher levels correlated with the risk of major adverse cardiac events. The current review aims to present the current evidence on diagnostic, prognostic and potentially therapeutic roles of IPF in cardiovascular medicine.

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y12 Inhibitors and Their Association with Platelet Function.

INTRODUCTION: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y12 inhibitors while assessing their association with platelet activity and turnover parameters. MATERIALS AND METHODS: We recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups. RESULTS: Analyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from -1.43 to -1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF. CONCLUSIONS: The identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587).

Comparative Appraisal of Intravascular Ultrasound and Optical Coherence Tomography in Invasive Coronary Imaging: 2022 Update.

Although coronary angiography has been well established as a standard modality for percutaneous coronary intervention guidance, recent developments in intravascular imaging techniques, such as intravascular ultrasound and optical coherence tomography, have become increasingly adopted, enabling direct detailed lesion visualization, including lesions beyond the scope of assessment using exclusively angiography. Intravascular imaging modalities have been reported to potentially improve both short- and long-term percutaneous intervention outcomes. This review aims to provide a comparative summary of recent advancements in research regarding the clinical applications and outcomes of intravascular ultrasound and optical coherence tomography.

Atherogenesis in Native Coronary Segments and In-Stent Neoatherogenesis Beyond Three Years After First-Generation Drug-Eluting Stent Implantation: Angiographic and Optical Coherence Tomography Study.

OBJECTIVES: The mechanisms underlying the development of neoatherosclerosis following stent implantation remain to be further elucidated. The aim of this study was to investigate the association between subclinical in-stent neoatherosclerosis (NA) and atherosclerosis progression of native coronary segments in patients with chronic coronary syndrome 3 and 9 years after first-generation drug-eluting stent implantation. METHODS: This is a prespecified analysis of the prospective cohort study evaluating long-term neointimal healing in consecutive patients undergoing elective percutaneous coronary intervention with sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) implantation. Quantitative coronary angiography (QCA) was evaluated in non-stented coronary segments. RESULTS: Forty-three patients underwent optical coherence tomography (OCT) and QCA at 3 years and 21 patients at 3 years and 9 years after SES or PES implantation. NA was identified in 44.2% at 3 years and in 66.7% at 9 years after the index procedure. NA at 3 years was more frequently observed in patients with atherosclerosis progression in native coronary segments than without (66.7% vs 15.8%; P<.01). Higher low-density cholesterol level (93 mg/dL vs 77 mg/dL; P=.04), greater maximal neointimal thickness (0.74 mm vs 0.37 mm; P<.001), and presence of peristrut low-intensity areas (57.9% vs 20.8%; P=.01) were more frequent in patients with NA. NA progression (P=.01) along with greater neointimal growth (P<.01) were detected in serial analysis between 3-year and 9-year OCT assessments. CONCLUSIONS: OCT-confirmed NA formation after first-generation drug-eluting stent implantation was associated with QCA-defined atherosclerosis progression in non-stented segments between 0 and 3 years. NA and neointimal proliferation continued between 3 and 9 years.

OCT-Derived Plaque Morphology and FFR-Determined Hemodynamic Relevance in Intermediate Coronary Stenoses.

BACKGROUND: optical coherence tomography (OCT) might allow identifying lesion features reportedly associated with plaque vulnerability and increased risk of clinical events. Previous studies on correlation between OCT and functional lesion significance indices reported contradictory results, yet integration of complementary information from both modalities is gaining increased interest. The aim of the study was to compare plaque morphology using OCT in hemodynamically relevant vs. non-relevant lesions by fractional flow reserve (FFR). METHODS: consecutive patients with intermediate grade coronary stenoses by angiography were evaluated by both FFR and OCT in this single-center study. Stenoses were labeled hemodynamically relevant in case of the FFR ≤ 0.80. Minimal lumen area (MLA), fibrous cap thickness (FCT), minimal cap thickness over the calcium, angle of the calcium, and necrotic core within the lesions were evaluated. RESULTS: a total of 105 patients (124 vessels) were analyzed. Of them, 65 patients were identified with at least one lesion identified as hemodynamically relevant by FFR (72 vessels, 58.1%). Lesions with FFR ≤0.80 presented with lower mean and minimal lumen area (3.46 ± 1.29 vs. 4.65 ± 2.19, p =0.001 and 1.84 ± 0.97 vs. 2.66 ± 1.40, p = 0.001) compared to patients with FFR > 0.80. No differences were found between groups in the mean and minimal FCT, mean, and maximal necrotic core, calcium angle, as well as the overall rate of calcified and lipid plaques. CONCLUSION: hemodynamic relevance of intermediate grade lesions correlated moderately with the luminal assessment by OCT. No differences were identified in the plaque morphology between relevant and non-relevant coronary stenoses by FFR.

Platelet to red cell distribution width ratio for predicting clopidogrel efficacy in patients undergoing percutaneous coronary interventions: insights from the ONSIDE-TEST study.

INTRODUCTION Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel remains a cornerstone of pharmacotherapy after percutaneous coronary intervention (PCI). It has been demonstrated that even up to 30% of patients receiving DAPT have inadequate response to clopidogrel, namely, high on­treatment platelet reactivity (HPR). The platelet to red cell distribution width (P­RDW) ratio represents an indicator of cardiovascular risk and may be related to HPR. OBJECTIVES The aim of the present study was to establish whether the P­RDW ratio predicts HPR in clopidogrel­treated patients undergoing elective PCI. PATIENTS AND METHODS This was a subanalysis of the prospective randomized­controlled ONSIDE TEST study. A total of 70 patients were included in the analysis, of whom 12 were identified with HPR. The HPR was defined as the values above the threshold of 208 platelet reactivity units (PRU >208) by the VerifyNowP2Y12 assay. RESULTS The P­RDW ratio was lower in patients with HPR than in those without HPR (mean [SD], 14.37 [4.13] vs 17.734 [4.96]; P = 0.03). A logistic regression analysis showed that the P­RDW ratio was associated with HPR (P = 0.03). Using a cut­off level of 15.23, the P­RDW ratio predicted HPR with a sensitivity of 69% and specificity of 75% (odds ratio, 6.67; 95% CI, 0.561-0.890; P = 0.02; are under the receiver operating characteristic curve, 0.723). CONCLUSIONS The P­RDW ratio may serve as a supplementary tool for identification of patients at risk of HPR. Further studies are warranted to assess its role in planning DAPT among patients undergoing PCI.