Abstract Ischaemia−reperfusion (IR) injury is an important cause of myocardial damage during percutaneous coronary intervention (PCI). There are few therapies in widespread clinical use which impact ...on IR injury and it remains an important and underutilized target for treatment in acute myocardial infarction. This review will examine the translational scientific evidence for ischaemic conditioning and pharmacological agents including conditioning mimetics such as cyclosporine, anti-inflammatory agents, and those which modify myocardial glucose metabolism. We will address the reasons why many trials have failed to demonstrate clinical benefit and emphasize the need to deliver the right therapy to the right patient, at the right time to achieve successful translation of cardioprotection from bench-to-bedside. We critique trial design and offer advice for future translational trials in the field to ensure that effective treatments can be demonstrated clinically to improve patient outcomes during PCI.
GLP-1 Is a Coronary Artery Vasodilator in Humans Clarke, Sophie J; Giblett, Joel P; Yang, Lucy L ...
Journal of the American Heart Association,
11/2018, Letnik:
7, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Background The mechanism underlying the beneficial cardiovascular effects of the incretin GLP-1 (glucagon-like peptide 1) and its analogues in humans is elusive. We hypothesized that activating ...receptors located on vascular smooth muscle cells to induce either peripheral or coronary vasodilatation mediates the cardiovascular effect of GLP -1. Methods and Results Ten stable patients with angina awaiting left anterior descending artery stenting underwent forearm blood flow measurement using forearm plethysmography and post-percutaneous coronary intervention coronary blood flow measurement using a pressure-flow wire before and after peripheral GLP -1 administration. Coronary sinus and artery bloods were sampled for GLP -1 levels. A further 11 control patients received saline rather than GLP -1 in the coronary blood flow protocol. GLP -1 receptor (GLP-1R) expression was assessed by immunohistochemistry using a specific GLP -1R monoclonal antibody in human tissue to inform the physiological studies. There was no effect of GLP -1 on absolute forearm blood flow or forearm blood flow ratio after GLP -1, systemic hemodynamics were not affected, and no binding of GLP -1R monoclonal antibody was detected in vascular tissue. GLP -1 reduced resting coronary transit time (mean SD , 0.87 0.39 versus 0.63 0.27 seconds; P=0.02) and basal microcirculatory resistance (mean SD , 76.3 37.9 versus 55.4 30.4 mm Hg/s; P=0.02), whereas in controls, there was an increase in transit time (mean SD, 0.48 0.24 versus 0.83 0.41 seconds; P<0.001) and basal microcirculatory resistance (mean SD, 45.9 34.7 versus 66.7 37.2 mm Hg/s; P=0.02). GLP -1R monoclonal antibody binding was confirmed in ventricular tissue but not in vascular tissue, and transmyocardial GLP -1 extraction was observed. Conclusions GLP -1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP -1R immunohistochemistry suggests that GLP -1 coronary vasodilatation is indirectly mediated by ventricular-coronary cross talk.
To assess the relationship between anatomical form and physiological function in atherosclerotic coronary arteries.
Although adverse cardiovascular events are predicted by plaque morphology or ...invasively-derived hemodynamic indices, the link between these important prognostic measures remains unexplored.
Patients with stable angina underwent fractional flow reserve (FFR), coronary flow reserve (CFR), pressure-derived collateral flow index (CFIp), trans-myocardial biomarker sampling and radiofrequency intravascular ultrasound (IVUS) imaging prior to intervention. Physiological ischemia was defined as either FFR≤0.8 or CFR<2.0.
Mean FFR was 0.70±0.15 and CFR was 2.1±1.3, with 68/92 lesions having FFR≤0.8 and 61/92 having CFR<2.0. On IVUS, FFR≤0.8 lesions had reduced minimal luminal area (MLA, p=0.03), increased plaque burden (PB, p=0.04) and volume (p=0.01). There was no relationship between FFR and IVUS-defined plaque composition. FFR≤0.8 was observed in 75.3%, 72.4% and 70.4% of lesions with MLA≤4mm2, PB≥70% and thin-cap fibroatheroma, respectively. Multivariate regression demonstrated FFR≤0.8 was independently predicted by MLA (odds ratio (OR) 0.53, 95% CI 0.29–0.97, p=0.04) and PB (OR 1.10, 95% CI 1.01–1.21, p=0.03). There were no identifiable relationships between plaque structure and CFR or CFIp. CFR<2.0 was associated with whole vessel necrotic core increases (p=0.047), fibrofatty tissue reduction (p=0.004) and elevated baseline transmyocardial high-sensitivity C-reactive protein (hsCRP) gradients (p=0.02).
Measures of plaque structure including PB and MLA are independently associated with FFR, but not with CFR or CFIp. Instead, vessels with low CFR have increased lipid accumulation and a higher transmyocardial hsCRP gradient. These results may explain similarities in clinical outcomes between physiologically and anatomically orientated trials.
Remote Ischemic Conditioning in Elective PCI? Giblett, Joel P.; Hoole, Stephen P.
Journal of cardiovascular pharmacology and therapeutics,
07/2017, Letnik:
22, Številka:
4
Journal Article
This review examines the rationale for using remote ischemic conditioning (RIC) in elective percutaneous coronary intervention (PCI) to prevent procedure-related ischemia–reperfusion injury and ...justifies the importance of periprocedural biomarker elevation following elective PCI as a valid target for RIC. We review the evidence for the use of RIC as a treatment in this setting and document the salutary rules that must be followed to successfully translate RIC for clinical benefit.
The role of glycoprotein IIb/IIIa inhibitors (GPI) in primary percutaneous coronary intervention (PPCI) remains uncertain. Previous analyses compare PPCI outcomes with clopidogrel plus GPI, versus ...without GPI. This does not reflect modern contemporary PPCI practice with ticagrelor or prasugrel. Nor does it answer the important question faced daily by PPCI operators: should GPI be used routinely or selectively? We aim to determine whether a strategy of routine use of GPI in contemporary PPCI practice is superior to selective GPI use. A total of 110,327 consecutive PPCIs performed in England were prospectively recorded in the British Cardiovascular Intervention Society Database (2009 to 2015). The cohort was divided into routine and selective GPI usage groups based on the PPCI operator's strategy, defined as GPI used in >75% and <25% PPCIs, respectively. Overall, GPI use declined from 73.1% to 43.3% of PPCIs. Routine compared with selective GPI usage was associated with lower all-cause 1-year mortality: 9.7% versus 11.0%, p < 0.001. There was a consistent survival benefit for routine GPI usage as compared with selective GPI usage: univariable analysis (hazard ratio = 0.88 95% confidence interval 0.83 to 0.93, p < 0.001), multivariable analysis (hazard ratio = 0.82 0.77 to 0.88, p < 0.001). For survival, there was no interaction between GPI usage and the type of P2Y12-inhibitor used. In conclusion, a strategy of routine GPI usage in patients who underwent PPCI was associated with lower all-cause mortality as compared with selective GPI usage. This benefit was maintained despite 44.3% of patients receiving prasugrel or ticagrelor.
Intravascular imaging has defined various vulnerable plaque (VP) phenotypes that predict future clinical events. Atherosclerosis is an inflammatory process and inflammation, measured by systemic ...biomarkers can also predict events and anti-inflammatory therapy is beneficial. We were interested to assess the relationship between plaque phenotypes and key inflammatory biomarkers, measured close to the coronary.
Ninety-two patients scheduled for elective percutaneous coronary intervention (PCI) underwent virtual histology intravascular ultrasound, optical coherence tomography, pressure wire and blood sampling from the guide catheter (GC), coronary sinus (CS) to determine trans-myocardial gradient (TMG = CS-GC) and from peripheral blood. Procedure related troponin release was assessed at 6-hours post-PCI from peripheral venous blood. Biomarker data were analysed and compared with coronary data.
Interleukin (IL)-6 was associated with increased levels of tumour necrosis factor (TNF)-α and C-reactive protein (CRP) and the pre-PCI IL-6 TMG correlated with plaque features of vulnerability: plaque burden - PB (r = 0.253, p = 0.04) and minimal lumen area - MLA (r = −0.438, p = 0.007), although no relationship existed for thin-capped fibroatheroma defined by either imaging modality. Peripheral IL-6 levels had no correlation with post PCI troponin, although the pre-PCI IL-6 TMG was related (r = 0.334, p = 0.006), as was PB (r = 0.27, p = 0.029).
IL-6 TMG pre-PCI correlates with plaque burden and MLA that have been shown to predict future clinical events and is correlated with post-PCI troponin release. These associations were not apparent from peripheral blood and suggest that local coronary biomarker signatures may help further define vulnerability and risk.
•Transmyocardial sampling can be used to discriminate cardiac production of biomarkers.•Transmyocardial gradient of Interleukin-6 correlates with established imaging markers of plaque vulnerability.•Periprocedural troponin elevation occurred more frequently in those with a high pre-PCI transmyocardial gradient of Interleukin-6.
The incretin hormone glucagon-like peptide 1 (GLP-1) has been shown to protect against lethal ischemia-reperfusion injury in animal models and against nonlethal ischemia reperfusion injury in humans. ...Furthermore, GLP-1 receptor agonists have been shown to reduce major adverse cardiovascular and cerebrovascular events (MACCE) in large-scale studies. We sought to investigate whether GLP-1 reduced percutaneous coronary intervention (PCI)–associated myocardial infarction (PMI) during elective PCI.
The study was a randomized, double-blind controlled trial in which patients undergoing elective PCI received an intravenous infusion of either GLP-1 at 1.2 pmol/kg/min or matched 0.9% saline placebo before and during the procedure. Randomization was performed in 1:1 fashion, with stratification for diabetes mellitus. Six-hour cardiac troponin I (cTnI) was measured with a primary end point of PMI defined as rise ≫×5 upper limit of normal (280 ng/L). Secondary end points included cTnI rise and MACCE at 12 months.
A total of 192 patients were randomized with 152 (79%) male and a mean age of 68.1 ± 8.9 years. No significant differences in patient demographics were noted between the groups. There was no difference in the rate of PMI between GLP-1 and placebo (9 9.8% vs 8 8.3%, P = 1.0) or in the secondary end points of difference in median cTnI between groups (9.5 0-88.5 vs 20 0-58.5 ng/L, P = .25) and MACCE at 12 months (7 7.3% vs 9 9.4%, P = .61).
In this randomized, placebo-controlled trial, GLP-1 did not reduce the low incidence of PMI or abrogate biomarker rise during elective PCI, nor did it influence the 12-month MACCE rate which also remained low.
Clinicaltrials.gov Number: NCT02127996https://clinicaltrials.gov/ct2/show/NCT02127996
Observational studies have shown that migraine has been associated with patent foramen ovale (PFO). Whilst studies investigating PFO closure for the treatment of migraine have been neutral, there is ...some evidence that symptoms of migraine may improve if the PFO was closed after ischemic stroke.
To establish whether closure of PFO in patients with stroke or transient ischemic attack (TIA) is associated with reduction in the severity of co-existent migraine headaches.
Patients with ischemic stroke or TIA, PFO suitable for percutaneous closure and migraine, were given migraine severity questionnaires prior to PFO closure. These were followed up at 6 and 12 months after closure with the same questionnaire. The primary endpoint was change in migraine severity using the Migraine Severity Scale (MIGSEV). Migraine episode frequency, disability (using the MIDAS scale), and pain intensity were also assessed.
Sixty-two patients were included in the analysis. MIGSEV scores reduced from 7 (7-8) at baseline to 4 (3.25-6) at 6-month follow-up, and 3 (0-4) at 12-month follow-up (
< 0.001). Other measures of migraine headache were also improved at both 6- and 12-month follow-up. Twenty-four (38%) patients were rendered migraine free at 12 months.
PFO closure for stroke or TIA prevention in patients with migraine was associated with a reduction in markers of migraine headache severity.
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