The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery ...disease.
Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease.
A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure–facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life EQ-5D) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up.
Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units 18%; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803).
Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina CorMicA; NCT03193294)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide linked to vascular diseases through a common intronic gene enhancer (rs9349379-G allele), chromosome 6 (PHACTR1/EDN1). We performed a ...multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction (CMD) in patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (CAD).
Three hundred and ninety-one patients with angina were enrolled. Of these, 206 (53%) with obstructive CAD were excluded leaving 185 (47%) eligible. One hundred and nine (72%) of 151 subjects who underwent invasive testing had objective evidence of CMD (COVADIS criteria). rs9349379-G allele frequency was greater than in contemporary reference genome bank control subjects allele frequency 46% (129/280 alleles) vs. 39% (5551/14380); P = 0.013. The G allele was associated with higher plasma serum ET-1 least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10-0.53; P = 0.005. Patients with rs9349379-G allele had over double the odds of CMD odds ratio (OR) 2.33, 95% CI 1.10-4.96; P = 0.027. Multimodality non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5 T (N = 107; GG 56%, AG 43%, AA 31%, P = 0.042) and exercise testing (N = 87; -3.0 units in Duke Exercise Treadmill Score; -5.8 to -0.1; P = 0.045). Endothelin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ETA) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ETA antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status.
We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ETA antagonist therapy in patients with microvascular angina.
ClinicalTrials.gov: NCT03193294.
Abstract Introduction There remains concern that the antiplatelet effects of aspirin and clopidogrel vary between patients and poor responders may be at increased risk of adverse events. However, the ...optimal method of measuring aspirin and/or clopidogrel response remains unresolved. We compared three methods of measuring clopidogrel response recommended by a recent consensus statement for the European Society of Cardiology, and investigated a novel approach to measuring aspirin response in patients established on both aspirin and clopidogrel. In addition, we investigated whether any of these assays predict peri-procedural myocardial necrosis following percutaneous coronary intervention (PCI). Methods A cross-section of 323 patients attending for PCI was tested for clopidogrel response using VerifyNow P2Y12, VASP Platelet Reactivity Index (VASP-PRI) and whole blood impedance aggregometry (WBPA). Aspirin response was assessed by measuring the residual ability of platelets to generate thromboxane, calculated as the difference between thromboxane B2 levels in serum and plasma, TxB2S-P . Peri-procedural myocardial necrosis was determined by a change in troponin I > 0.2 μmol/l. Results Patients demonstrated wide variation in response to both aspirin and clopidogrel. Correlation between VerifyNow P2Y12 and VASP-PRI was good (r = 0.702, p < 0.001). Correlation was moderate between WBPA and VerifyNow P2Y12 (r = 0.639, p < 0.001) and weak for WBPA and VASP-PRI (r = 0.353, p < 0.001). Only VerifyNow P2Y12 predicted peri-procedural myocardial necrosis. Conclusions The three methods of measuring response to clopidogrel identify different patients as poor responders. Poor response to clopidogrel assessed by VerifyNow P2Y12 predicts myocardial necrosis. Measurement of TxB2S-P demonstrates a wide variation in aspirin response in patients taking dual antiplatelet therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cessation of one component of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has been associated with increased risk of ischemic events but it is uncertain ...whether discontinuation of aspirin is preferable to discontinuation of the oral P2Y
12
inhibitor. The GLOBAL LEADERS study compared two antiplatelet strategies following PCI, cessation of aspirin at 1 month with continued ticagrelor monotherapy for 23 months versus standard DAPT for 12 months followed by aspirin monotherapy for a further 12 months. We assessed recovery of platelet reactivity after withdrawal of either aspirin or ticagrelor at 1 month and 12 months, respectively, in this study. Platelet aggregation (PA) was assessed before cessation of DAPT ('baseline') and after 2, 7, and 14 days post-cessation using Multiplate whole-blood aggregometry with collagen, thrombin-receptor-activating peptide (TRAP), adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists. Following cessation of aspirin at 1 month, there was marked recovery of PA induced by AA (baseline mean ± SD: 11.1 ± 7.4 U vs. 14 days: 64.9 ± 19.6 U, p < .0001) and collagen (37.4 ± 22.9 U vs. 79.8 ± 13.8 U, p < .0001), whereas PA induced by ADP (18.6 ± 6.6 vs. 69.1 ± 20.5, p < .0001) and collagen (34.4 ± 18.7 U vs. 43.0 ± 21.0, p = .0018) recovered following cessation of ticagrelor at 12 months. There were no significant changes in TRAP-induced PA in either group. In conclusion, cessation of either component of DAPT leads to substantial increase in platelet reactivity with differential effects on different pathways of platelet activation when aspirin or the P2Y
12
inhibitor is stopped. Further work is required to determine which patients receive net benefit from long-term continuation of DAPT.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Principal component analysis (PCA) is a technique commonly used for fault detection and classification (FDC) in highly automated manufacturing. Because PCA model building and adaptation rely on ...eigenvalue decomposition of parameter covariance matrices, the computational effort scales cubically with the number of input variables. As PCA-based FDC applications monitor systems with more variables, or trace data with faster sampling rates, the size of the PCA problems can grow faster than the FDC system infrastructure will allow. This paper introduces an algorithm that greatly reduces the overall size of the PCA problem by breaking the analysis of a large number of variables into multiple analyses of smaller uncorrelated blocks of variables. Summary statistics from these subanalyses are then combined into results that are comparable to what is generated from the complete PCA of all variables together.
Background The objective of the GNOCCI (Glasgow Natural History Study of Covered Stent Coronary Interventions) Study was to report the incidence and outcomes of coronary artery perforations over an ...18‐year period at a single, high‐volume percutaneous coronary intervention center. We considered both the temporal trends and long‐term outcomes of covered stent deployment. Methods and Results We evaluated procedural and long‐term clinical outcomes following coronary perforation in a cohort of 43,343 consecutive percutaneous coronary intervention procedures. Procedural major adverse cardiac events were defined as a composite of death, myocardial infarction, stroke, target vessel revascularization, or cardiac surgery within 24 hours. A total of 161 (0.37%) procedures were complicated by coronary perforation of which 57 (35%) were Ellis grade III. Incidence increased with time over the study period ( r =0.73; P <0.001). Perforation severity was linearly associated with procedural mortality (median 2.9‐year follow‐up): Ellis I (0%), Ellis II (1.7%), Ellis III/IIIB (21%), P <0.001. Procedural major adverse cardiac events occurred in 47% of patients with Ellis III/IIIB versus 13.5% of those with Ellis I/II perforations (odds ratio, 5.8; 95% CI, 2.7–12.5; P <0.001). Covered stents were associated with an increased risk of stent thrombosis at 2.9‐year follow‐up (Academic Research Consortium definite or probable; 9.1% versus 0.9%; risk ratio, 10.5; 95% CI, 1.1–97; P =0.04). Conclusions The incidence of coronary perforation increased between 2001 and 2019. Severe perforation was associated with higher procedural major adverse cardiac events and was an independent predictor of long‐term mortality. Although covered stents are a potentially lifesaving treatment, the generation of devices used during the study period was limited by their efficacy and high risk of stent thrombosis. Registration Information Clinicaltrials.gov. Identifier: NCT03862352.
Abstract
Dual antiplatelet therapy with aspirin and a P2Y12 antagonist is widely prescribed for the prevention of thrombotic events in patients with an acute coronary syndrome or undergoing ...percutaneous coronary intervention (PCI). It is recognised that there is inter-individual variation in the antiplatelet effects of both drugs. Recent data also suggest that P2Y12 antagonists can affect the response to aspirin. A direct indicator of the effect of aspirin on platelets is their ability to generate thromboxane, which if measured as the difference between the level of thromboxane B2 in serum and plasma (TxB2S-P) avoids the confounding effect of endogenous TxB2 production from other cells. We therefore analysed TxB2S-P as a measure of aspirin response in a group of 123 patients undergoing elective PCI before and after the introduction of clopidogrel. In a subgroup of 40 patients taking aspirin alone, we compared TxB2S-P and VerifyNow Aspirin for the assessment of aspirin response. There was a wide variation in plasma and serum TxB2 concentrations both before and after clopidogrel therapy but only 3.5% of patients had residual serum concentration of TxB2 > 10 ng/ml. There was a strong correlation between the pre and post clopidogrel levels of TxB2 (r 0.78; p = 0.001) and no significant difference in TxB2S-P. There was no correlation between the magnitude of response to clopidogrel response and the generation of thromboxane B2. Correlation between TxB2S-P and VerifyNow Aspirin was poor. We conclude that the use of a P2Y12 antagonist does not influence the effect of aspirin on the ability of platelets to generate thromboxane. Therefore, measurement of TxB2 levels in serum, after subtracting the contribution from plasma, provides a measure of the response to aspirin in patients taking dual antiplatelet therapy.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Transcatheter aortic valve implantation (TAVR) has grown rapidly over the past 10 years. Device and delivery catheter systems have evolved to facilitate the procedure and reduce the risk of ...associated complications, including those related to vascular access. It is important to understand the utility of the TAVR equipment in patients with more challenging anatomy to select the most appropriate technique for this complex procedure. We report the first case, to our knowledge, of a patient with dextrocardia situs inversus and previous coronary artery bypass grafting who underwent TAVR from the femoral route using the Edwards SAPIEN XT Novaflex+ Transfemoral System (Edwards Lifesciences, Irvine, CA).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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