scholarly journals Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

2021 ◽  
Vol 22 (19) ◽  
pp. 10270
Author(s):  
Saveria Femminò ◽  
Fabrizio D’Ascenzo ◽  
Francesco Ravera ◽  
Stefano Comità ◽  
Filippo Angelini ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Extracellular Vesicles ◽  
Ex Vivo ◽  
Coronary Intervention ◽  
Protective Properties ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
Mrna Content ◽  
The Impact

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) (NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability.

scholarly journals Long-term impact of baseline anaemia on clinical outcomes following percutaneous coronary intervention in stable angina

Open Heart ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. e001319
Author(s):  
Line Davidsen ◽  
Kristian Hay Kragholm ◽  
Mette Aldahl ◽  
Christoffer Polcwiartek ◽  
Christian Torp-Pedersen ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Clinical Outcomes ◽  
Stable Angina ◽  
Coronary Intervention ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
All Cause Mortality ◽  
The Impact

BackgroundIn patients with stable angina (SA), the clinical benefits of percutaneous coronary intervention (PCI) reside almost exclusively within the realm of symptomatic improvement rather than improvement in hard clinical endpoints. The benefits of PCI should always be balanced against its potential short-term and long-term risks. Common among these risks is the presence of anaemia and its interaction with poor clinical outcomes and increased morbidity; this study aims to elucidate the impact of anaemia on long-term clinical outcomes of this patient group.MethodsFrom Danish national registries, we identified patients with SA treated with PCI who had a haemoglobin measurement maximum of 90 days prior to PCI procedure. Anaemia was defined as haemoglobin <130 and <120 g/L in men and women, respectively. Follow-up was up to 3 years after PCI, and Cox regression was used to estimate HRs with 95% CIs of hospitalisation due to bleeding, acute coronary syndrome (ACS) and all-cause mortality in patients with anaemia compared with patients without anaemia.ResultsOf 2837 included patients, 14.6% had anaemia prior to PCI. During follow-up, 93 patients (3.3%) had a bleeding episode, which was higher in patients with anaemia (5.8%) compared with patients without anaemia (2.8%). A total of 213 patients (7.5%) developed ACS, which was higher in patients with anaemia (10.6%) compared with patients without anaemia (7.0%). Furthermore, 185 patients (6.5%) died, with a mortality rate of 18.1% in patients with anaemia compared with 4.5% in patients without anaemia. In multivariable analyses, anaemia was associated with a significantly increased risk of bleeding (HR 1.69; 95% CI 1.04 to 2.73; P 0.033), ACS (HR 1.47; 95% CI 1.04 to 2.10; P 0.031) and all-cause mortality (HR 2.41; 95% CI 1.73 to 3.30; P <0.001).ConclusionAnaemia in patients with SA was significantly associated with bleeding, ACS and all-cause mortality following PCI.

scholarly journals The potential interaction of statins and clopidogrel in patients undergoing percutaneous coronary intervention

2021 ◽  
Vol 8 (3) ◽  
pp. 112-119
Author(s):  
Ibrahim et al. ◽  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Intervention ◽  
Potential Interaction ◽  
Cardiac Events ◽  
Cross Sectional ◽  
Beneficial Effects ◽  
Coronary Syndrome ◽  
Adverse Cardiac Events ◽  
Percutaneous Coronary ◽  
The Impact

Clopidogrel is widely used for patients with acute coronary syndrome. It is a pro-drug that requires bioactivation by several cytochrome P450 (CYP) enzymes, mainly CYP3A4, CYP2C9, and CYP2C19 enzymes. Lipophilic statins such as atorvastatin are used concomitantly with clopidogrel due to their beneficial effects on morbidity and mortality in the arena of cardiovascular diseases. However, lipophilic statins are eliminated by CYP3A4 and undergo the same metabolic pathway of clopidogrel. Hence, statins may compete with clopidogrel for CYP3A4 enzyme resulting in diminishing the anti-platelet effect of clopidogrel. We aimed to study the impact of concomitant statin therapy on clopidogrel efficacy in patients undergoing percutaneous coronary intervention (PCI) evaluate the clinical relevance of potential clopidogrel and statins interaction and association between use of statins and risk of future adverse cardiac events. A cross-sectional retrospective cohort study was conducted on 50 patients attending Prince Sultan Cardiac Center for follow-up after PCI. All patients discharged on clopidogrel, aspirin, and atorvastatin were later divided into two groups according to the occurrence of MACEs. Statistical analysis was performed by Statistical Package for the Social Science (SPSS; V. 21.0). This study was on adult and geriatric males (72%)and female (28%). More than half of them exhibited major adverse cardiac events (MACEs), of which 48% exhibited it after 4 to 6 months from PCI indexing followed by 1 to 3 months (34%), and the least after 7 to 9 months. A significant association arises between gender and MACEs (P=0.042). Moreover, the average age was significantly higher in patients who experience MACEs compared to others (62.7 vs. 55.4, P=0.037). Regarding comorbidities, hypertension increased in patients with MACEs (73.1%) compared to those without MACEs (45.8%). The average duration of taking clopidogrel was significantly shorter in patients with MACEs compared to those who did not (3.42 vs. 5.54 months, P<0.001). According to the findings of this study, atorvastatin affects clopidogrel efficacy in patients undergoing PCI.

scholarly journals Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Kaivan Vaidya ◽  
Bradley Tucker ◽  
Rahul Kurup ◽  
Chinmay Khandkar ◽  
Elvis Pandzic ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Angina Pectoris ◽  
Colchicine Treatment ◽  
Coronary Intervention ◽  
Healthy Controls ◽  
Stable Angina Pectoris ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Background Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with periprocedural myocardial infarction, as a result of microvascular obstruction via pro‐inflammatory and prothrombotic pathways. Colchicine is a well‐established anti‐inflammatory agent with growing evidence to support use in patients with coronary disease. However, its effects on post‐PCI NET formation in ACS have not been explored. Methods and Results Sixty patients (40 ACS; 20 stable angina pectoris) were prospectively recruited and allocated to colchicine or no treatment. Within 24 hours of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 patients with ACS post‐PCI and 4 healthy controls were treated in vitro with colchicine (25 nmol/L) and stimulated with either ionomycin (5 μmol/L) or phorbol 12‐myristate 13‐acetate (50 nmol/L). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst 3342 and anti‐alpha tubulin. Baseline characteristics were similar across both treatment and control arms. Patients with ACS had higher NET release versus patients with stable angina pectoris ( P <0.001), which was reduced with colchicine treatment (area under the curve: 0.58 versus 4.29; P <0.001). In vitro, colchicine suppressed unstimulated ( P <0.001), phorbol 12‐myristate 13‐acetate–induced ( P =0.009) and ionomycin‐induced ( P =0.002) NET formation in neutrophils isolated from patients with ACS post‐PCI, but not healthy controls. Tubulin organization was impaired in neutrophils from patients with ACS but was restored by colchicine treatment. Conclusions Colchicine suppresses NET formation in patients with ACS post‐PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomized trials powered for clinical end points. Registration URL: https://anzctr.org.au ; Unique identifier: ACTRN12619001231134.

scholarly journals Cardiac procedural myocardial injury, infarction, and mortality in patients undergoing elective percutaneous coronary intervention: a pooled analysis of patient-level data

2020 ◽  
Author(s):  
Johanne Silvain ◽  
Michel Zeitouni ◽  
Valeria Paradies ◽  
Huili L Zheng ◽  
Gjin Ndrepepa ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Myocardial Injury ◽  
High Sensitivity ◽  
Fold Increase ◽  
Coronary Intervention ◽  
Reference Limit ◽  
Coronary Syndrome ◽  
Elective Percutaneous Coronary Intervention ◽  
Percutaneous Coronary ◽  
The Impact

Abstract Aims The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Methods and results We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84–1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32–3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42–7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin). Conclusion Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect ‘major’ procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia.

scholarly journals Colchicine inhibits neutrophil extracellular trap formation in acute coronary syndrome patients after percutaneous coronary intervention

2020 ◽  
Author(s):  
Kaivan Vaidya ◽  
Bradley Tucker ◽  
Rahul Kurup ◽  
Chinmay Khandkar ◽  
Elvis Pandzic ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Colchicine Treatment ◽  
Coronary Intervention ◽  
Extracellular Dna ◽  
Neutrophil Extracellular Trap ◽  
Healthy Controls ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

ObjectiveRelease of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with peri-procedural myocardial infarction, as a result of microvascular obstruction via pro-inflammatory and pro-thrombotic pathways. Colchicine is a potent, well-established anti-inflammatory agent with growing evidence to support use in patients with coronary disease. However, its effects on post-PCI NET formation in ACS has not been explored.Approach and Results60 patients (40 ACS; 20 stable angina pectoris [SAP]) were prospectively recruited and allocated to colchicine or no treatment. Within 24 h of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 ACS patients post-PCI and 4 healthy controls were treated in vitro with colchicine (25 nM) and stimulated with either ionomycin (5 μM) or phorbol 12-myristate 13-acetate (PMA, 50 nM). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst and anti-alpha tubulin. Baseline characteristics were similar across both treatment and control arms. ACS patients had higher NET release versus SAP patients (p<0.001), which was reduced with colchicine treatment (AUC: 0.58 vs. 4.29; p<0.001). In vitro, colchicine suppressed spontaneous (p=0.004), PMA-induced (p=0.03) and ionomycin-induced (p=0.02) NET formation in neutrophils isolated from ACS patients post-PCI, but not healthy controls. Tubulin organisation was impaired in neutrophils from patients with ACS but was restored by colchicine treatment.ConclusionsColchicine suppresses NET formation in ACS patients post-PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomised trials powered for clinical endpoints.Graphical Abstract

Abstract 13302: The Depression and Anxiety Paradox Following Percutaneous Coronary Intervention: A National Inpatient Sample Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hawa O Abu ◽  
Efehi Igbinomwanhia ◽  
Olakanmi Olagoke ◽  
Abdulkareem O Lukan ◽  
Chiamaka S Diala ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Hospital Mortality ◽  
Clinical Outcomes ◽  
Length Of Hospital Stay ◽  
Clinical History ◽  
Coronary Intervention ◽  
Depression And Anxiety ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
The Impact

Introduction: Depression and Anxiety are prevalent among patients with cardiovascular diseases. However, their impact on important clinical outcomes, such as length of hospital stay (LOS) and mortality, is incompletely understood. Objective: Examine the magnitude and impact of major depressive disorder (MDD) and anxiety on LOS and in-hospital mortality in patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI). Hypothesis: Patients with MDD or anxiety will have poorer clinical outcomes after PCI. Methods: Data were obtained from the National Inpatient Survey (NIS). Admissions in 2017 with a primary diagnosis of ACS and undergoing PCI were identified based on ICD10 codes. Patients with MDD or anxiety were further delineated with ICD10 codes. The association between MDD or anxiety and LOS and in-hospital mortality was analyzed using linear and logistic regression models, respectively. Various sociodemographic (age, race, sex, income), clinical (history of hypertension, hyperlipidemia, stroke, peripheral artery disease, valvular heart disease, chronic kidney disease, anemia, obesity, smoking) and hospital-level (region, location, payer type) factors were adjusted for in the analysis. Results: Among 130,712 patients admitted for ACS who underwent PCI, the prevalence of MDD and anxiety were 8.7% (n=11,303) and 10.8% (n=14,066), respectively. Patients were on average aged 67 years (SD=13.5), 38% were females, and 73% non-Hispanic White. Overall, the mean LOS was 4.4 days (SD=5.4) and 4.7% of patients died while hospitalized. Patients with MDD (4.6 vs 4.4, p=0.001) or anxiety (4.7 vs 4.4, p=0.001) had longer LOS than those without these conditions. Contrary to our hypothesis, patients with MDD (OR: 0.82; 95% CI: 0.73-0.91) or anxiety (OR: 0.72; 95% CI: 0.64-0.79) had significantly lower odds of mortality than those without MDD or anxiety after adjusting for several factors of prognostic importance. Conclusions: Among ACS patients who underwent PCI, MDD and anxiety were associated with increased LOS but paradoxically lower in-hospital mortality. These findings reinforce the need for future investigations to evaluate the impact of psychological factors on clinical outcomes in ACS patients who undergo PCI.

scholarly journals Smoking status and mortality outcomes following percutaneous coronary intervention

2020 ◽  
pp. 204748732090232 ◽  
Author(s):  
Sathish Parasuraman ◽  
Azfar G Zaman ◽  
Mohaned Egred ◽  
Alan Bagnall ◽  
Paul A Broadhurst ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Smoking Status ◽  
Coronary Intervention ◽  
Study Cohort ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
Mortality Difference ◽  
Never Smokers ◽  
Public Message ◽  
The Impact

Objective The aim of this study was to assess the impact of smoking on short (30-day) and intermediate (30-day to 6-month) mortality following percutaneous coronary intervention (PCI). Background The effect of smoking on mortality post-PCI is lacking in the modern PCI era. Methods This was a retrospective analysis of prospectively collected data comparing short- and intermediate-term mortality amongst smokers, ex-smokers and non-smokers. Results The study cohort consisted of 12,656 patients: never-smokers ( n = 4288), ex-smokers ( n = 4806) and current smokers ( n = 3562). The mean age (±standard deviation) was 57 (±11) years in current smokers compared with 67 (±11) in ex-smokers and 67 (±12) in never-smokers; p < 0.0001. PCI was performed for acute coronary syndrome (ACS) in 84.1% of current smokers, 57% of ex-smokers and 62.9% in never-smokers; p < 0.0001. In a logistic regression model, the adjusted odds ratios (95% confidence intervals (CIs)) for 30-day mortality were 1.60 (1.10–2.32) in current smokers and 0.98 (0.70–1.38) in ex-smokers compared with never-smokers. In the Cox proportional hazard model, the adjusted hazard ratios (95% CI) for mortality between 30 days and 6 months were 1.03 (0.65–1.65) in current smokers and 1.19 (0.84–1.67) in ex-smokers compared with never-smokers. Conclusion This large observational study of non-selected patients demonstrates that ex-smokers and never-smokers are of similar age at first presentation to PCI, and there is no short- or intermediate-term mortality difference between them following PCI. Current smokers undergo PCI at a younger age, more often for ACS, and have higher short-term mortality. These findings underscore the public message on the benefits of smoking cessation and the harmful effects of smoking.

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