Prevalence and clinical impact of high platelet reactivity in patients with chronic kidney disease treated with percutaneous coronary intervention: An updated systematic review and meta-analysis.

BACKGROUND: High platelet reactivity (HPR) on clopidogrel and chronic kidney disease (CKD) are recognized as potent risk factors for adverse outcomes in patients suffering coronary artery disease (CAD) and undergoing percutaneous coronary intervention (PCI). However, conclusive evidence regarding their reciprocal interaction and the consequent impact on clinical events is still lacking. OBJECTIVES: We performed a metaanalysis with the aim to evaluate the prevalence of HPR in patients with and without CKD and the incidence of major adverse cardiovascular events (MACE) according to the renal and platelet function status in current literature (co-primary endpoints). Secondary endpoints were myocardial infarction (MI), all-cause death, and definite/probable stent thrombosis (ST). METHODS: We searched on PubMed, EMBASE, and Cochrane Library studies investigating CKD and HPR on clopidogrel in patients suffering CAD who underwent PCI and their related outcomes. Overall, 13 studies including 22.464 patients were selected. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using a random-effects model with the Mantel-Haenszel method. RESULTS: Patients with CKD presented significantly higher odds of HPR compared with those without CKD (OR 1.51 [95% CI: 1.29, 1.76]). In patients without CKD, HPR was associated with increased odds of MACE (OR 1.31 [95% CI: 1.01, 1.72]), MI (OR 1.48 [95% CI: 1.17, 1.86]) and definite/probable ST (OR 2.45 [95% CI: 1.08, 5.60]). In patients with CKD, HPR was associated with higher odds of both MACE (OR 1.61 [95% CI: 1.14, 2.27]) and MI (OR 1.69 [95% CI: 1.11, 2.59]), compared to those without HPR. CONCLUSIONS: Our analysis shows that HPR on clopidogrel is more frequent in patients with CKD treated with PCI. Patients with HPR are exposed to a high risk of MACE after PCI, regardless of the renal function status.

Effect of Interleukin-1 Blockade on Left Ventricular Systolic Performance and Work: A Post Hoc Pooled Analysis of 2 Clinical Trials.

BACKGROUND: Interleukin-1 (IL-1) blockade seems to improve anaerobic exercise in patients with systolic heart failure through improved left ventricular (LV) systolic performance. However, it is unclear whether IL-1 blockade affects LV systolic performance. METHODS: We pooled data from 2 clinical trials of patients with systolic heart failure who were randomized to IL-1 blockade or placebo. We estimated changes in LV systolic performance (LV ejection fraction [LVEF] and end-systolic elastance [LVEes]) and pressure-volume area (PVA), a surrogate of oxygen consumption, after 14 days of treatment. RESULTS: LVEF increased from 30% (24%-38%) to 36% (29%-43%) between baseline and day 14 only in anakinra-treated patients (P = 0.03 for within-group change and P = 0.02 for between-group change compared with placebo). LVEes increased from 1.0 mm Hg/mL (0.7-1.5) to 1.3 mm Hg/mL (0.8-1.6) in anakinra-treated patients between baseline and day 14 but not in placebo-treated patients (P = 0.03 for within-group change and P = 0.08 for between-group change). A change in PVA between baseline and 14 days was not detected in either anakinra or placebo patients. CONCLUSIONS: In this post hoc analysis, LVEes and LVEF increased significantly in patients treated with an IL-1 blocker but not in placebo-treated patients. An effect of IL-1 blockade on calculated PVA was not detected.

International evaluation of an artificial intelligence-powered electrocardiogram model detecting acute coronary occlusion myocardial infarction.

Aims: A majority of acute coronary syndromes (ACS) present without typical ST elevation. One-third of non-ST-elevation myocardial infarction (NSTEMI) patients have an acutely occluded culprit coronary artery [occlusion myocardial infarction (OMI)], leading to poor outcomes due to delayed identification and invasive management. In this study, we sought to develop a versatile artificial intelligence (AI) model detecting acute OMI on single-standard 12-lead electrocardiograms (ECGs) and compare its performance with existing state-of-the-art diagnostic criteria. Methods and results: An AI model was developed using 18 616 ECGs from 10 543 patients with suspected ACS from an international database with clinically validated outcomes. The model was evaluated in an international cohort and compared with STEMI criteria and ECG experts in detecting OMI. The primary outcome of OMI was an acutely occluded or flow-limiting culprit artery requiring emergent revascularization. In the overall test set of 3254 ECGs from 2222 patients (age 62 ± 14 years, 67% males, 21.6% OMI), the AI model achieved an area under the curve of 0.938 [95% confidence interval (CI): 0.924-0.951] in identifying the primary OMI outcome, with superior performance [accuracy 90.9% (95% CI: 89.7-92.0), sensitivity 80.6% (95% CI: 76.8-84.0), and specificity 93.7 (95% CI: 92.6-94.8)] compared with STEMI criteria [accuracy 83.6% (95% CI: 82.1-85.1), sensitivity 32.5% (95% CI: 28.4-36.6), and specificity 97.7% (95% CI: 97.0-98.3)] and with similar performance compared with ECG experts [accuracy 90.8% (95% CI: 89.5-91.9), sensitivity 73.0% (95% CI: 68.7-77.0), and specificity 95.7% (95% CI: 94.7-96.6)]. Conclusion: The present novel ECG AI model demonstrates superior accuracy to detect acute OMI when compared with STEMI criteria. This suggests its potential to improve ACS triage, ensuring appropriate and timely referral for immediate revascularization.

Platelet reactivity and clinical outcomes following percutaneous coronary intervention in complex higher-risk patients.

AIMS: To investigate the levels of platelet reactivity and the impact of high platelet reactivity (HPR) on long-term clinical outcomes of complex higher-risk and indicated patients (CHIP) with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI). METHODS: We enrolled 500 patients undergoing elective PCI for stable CAD and treated with aspirin and clopidogrel. Patients were divided into four groups based on the presence of CHIP features and HPR. Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. RESULTS: The prevalence of HPR was significantly greater in the CHIP population rather than non-CHIP patients (39.9% vs 29.8%, P = 0.021). Patients with both CHIP features and HPR showed the highest estimates of MACE (22.1%, log-rank P = 0.047). At Cox proportional hazard analysis, the combination of CHIP features and HPR was an independent predictor of MACE (hazard ratio 2.57, 95% confidence interval 1.30-5.05, P = 0.006). CONCLUSION: Among patients with stable CAD undergoing elective PCI and treated with aspirin and clopidogrel, the combination of CHIP features and HPR identifies a cohort of patients with the highest risk of MACE at 5 years, who might benefit from more potent antiplatelet strategies.

Instantaneous wave-free ratio-guided revascularization of non-culprit lesion in patients with ST-segment elevation myocardial infarction and multivessel coronary disease: design and rationale of the WAVE Registry.

BACKGROUND: The optimal management of patients with ST-elevation acute coronary syndromes and multivessel coronary artery disease is challenging. There is a growing body of evidence supporting invasive functional evaluation of multivessel disease with FFR or iFR, which it has been added to the literature. In this regard, the WAVE Study recently demonstrated the diagnostic accuracy of instantaneous wave-free ratio (iFR) functional assessment of non-culprit lesions in multivessel patients with STEMI. However, no studies have still verified the long-term clinical impact of an iFR-guided revascularization in this setting of patients. METHODS: Patients undergoing primary PCI for STEMI and presenting multivessel disease will be enrolled. After the treatment of the culprit lesion, an iFR-guided functional assessment of non-culprit lesions will be done if iFR≤0.89 PCI will be performed during the index procedure or staged. Conversely, iFR>0.89 will direct the patient towards a conservative approach. RESULTS: The study start date was May 1, 2018. The enrollment phase was completed on March 30, 2020. The primary endpoint is the occurrence of target lesion failure (TLF), a composite of cardiovascular death, non-fatal myocardial infarction, and ischemia-driven revascularization of the vessel previously assessed with iFR. Secondary endpoints include MACE (cardiovascular death, non-fatal MI, any revascularization). CONCLUSIONS: The aim of the present study was to evaluate the long-term clinical impact of an iFR-guided revascularization of the non-culprit lesions in STEMI patients with multivessel coronary artery disease.

Interleukin-1 blockade for the treatment of pericarditis.

Pericarditis is a debilitating condition that results from profound inflammation of the pericardial tissue. Between 10 and 15% of first episodes of acute pericarditis will be followed by several episodes refractory to conventional treatment. Current standard of care for pericarditis treatment includes high-dose non-steroidal anti-inflammatory drugs, colchicine, and systemic corticosteroids, each associated with potentially severe toxicities and nominal efficacy. Interleukin-1 (IL-1), an apical pro-inflammatory cytokine, plays an important role as an autocrine magnifier of systemic inflammation in pericarditis. Interruption of the IL-1 circuit has been shown to have a favourable risk profile in several disease states. In this review, we discuss the growing body of evidence which supports the use of IL-1 blockade in the treatment of recurrent pericarditis as well as provide practical considerations for the use of IL-1 blockade in clinical practice.