ST-segment elevation in patients presenting with COVID-19: case series.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the now pandemic disease, coronavirus disease (COVID-19). A number of reports have emerged suggesting these patients may present with signs and symptoms consistent with ST-segment elevation myocardial infarction without coronary artery occlusion. CASE SUMMARY: We report an international case series of patients with confirmed COVID-19 infection who presented with suspected ST-segment elevation myocardial infarction. Three patients with confirmed COVID-19 presented with electrocardiogram criteria for ST-segment elevation myocardial infarction. No patient had obstructive coronary disease at coronary angiography. Post-mortem histology in one case demonstrated myocardial ischaemia in the absence of coronary atherothrombosis or myocarditis. DISCUSSION: Patients with COVID-19 may present with features consistent with ST-segment elevation myocardial infarction and patent coronary arteries. The prevalence and clinical outcomes of this condition require systematic investigation in consecutive unselected patients.

Early Oxidative Stress Response in Patients with Severe Aortic Stenosis Undergoing Transcatheter and Surgical Aortic Valve Replacement: A Transatlantic Study.

Myocardial ischemia/reperfusion-related oxidative stress as a result of cardiopulmonary bypass is thought to contribute to the adverse clinical outcomes following surgical aortic valve replacement (SAVR). Although the acute response following this procedure has been well characterized, much less is known about the nature and extent of oxidative stress induced by the transcatheter aortic valve replacement (TAVR) procedure. We therefore sought to examine and directly compare the oxidative stress response in patients undergoing TAVR and SAVR. A total of 60 patients were prospectively enrolled in this exploratory study, 38 patients undergoing TAVR and 22 patients SAVR. Reduced and oxidized glutathione (GSH, GSSG) in red blood cells as well as the ferric-reducing ability of plasma (FRAP) and plasma concentrations of 8-isoprostanes were measured at baseline (S1), during early reperfusion (S2), and 6-8 hours (S3) following aortic valve replacement (AVR). TAVR and SAVR were successful in all patients. Patients undergoing TAVR were older (79.3 ± 9.5 vs. 74.2 ± 4.1 years; P < 0.01) and had a higher mean STS risk score (6.6 ± 4.8 vs. 3.2 ± 3.0; P < 0.001) than patients undergoing SAVR. At baseline, FRAP and 8-isoprostane plasma concentrations were similar between the two groups, but erythrocytic GSH concentrations were significantly lower in the TAVR group. After AVR, FRAP was markedly higher in the TAVR group, whereas 8-isoprostane concentrations were significantly elevated in the SAVR group. In conclusion, TAVR appears not to cause acute oxidative stress and may even improve the antioxidant capacity in the extracellular compartment.

True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study.

OBJECTIVE: To determine the distribution, and specifically the true 99th centile, of high sensitivity cardiac troponin I (hs-cTnI) for a whole hospital population by applying the hs-cTnI assay currently used routinely at a large teaching hospital. DESIGN: Prospective, observational cohort study. SETTING: University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, between 29 June 2017 and 24 August 2017. PARTICIPANTS: 20 000 consecutive inpatients and outpatients undergoing blood tests for any clinical reason. Hs-cTnI concentrations were measured in all study participants and nested for analysis except when the supervising doctor had requested hs-cTnI for clinical reasons. MAIN OUTCOME MEASURES: Distribution of hs-cTnI concentrations of all study participants and specifically the 99th centile. RESULTS: The 99th centile of hs-cTnI for the whole population was 296 ng/L compared with the manufacturer's quoted level of 40 ng/L (currently used clinically as the upper limit of normal; ULN). Hs-cTnI concentrations were greater than 40 ng/L in one in 20 (5.4%, n=1080) of the total population. After excluding participants diagnosed as having acute myocardial infarction (n=122) and those in whom hs-cTnI was requested for clinical reasons (n=1707), the 99th centile was 189 ng/L for the remainder (n=18 171). The 99th centile was 563 ng/L for inpatients (n=4759) and 65 ng/L for outpatients (n=9280). Patients from the emergency department (n=3706) had a 99th centile of 215 ng/L, with 6.07% (n=225) greater than the recommended ULN. 39.02% (n=48) of all patients from the critical care units (n=123) and 14.16% (n=67) of all medical inpatients had an hs-cTnI concentration greater than the recommended ULN. CONCLUSIONS: Of 20 000 consecutive patients undergoing a blood test for any clinical reason at our hospital, one in 20 had an hs-cTnI greater than the recommended ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the recommended ULN to diagnose acute myocardial infarction, in order to avoid misdiagnosis in the absence of an appropriate clinical presentation. TRIAL REGISTRATION: Clinicaltrials.gov NCT03047785.

Changes in platelet function with inflammation in patients undergoing vascular surgery.

The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesized, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP-, and thrombin-induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12-HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured pre-procedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin-induced platelet reactivity was assessed using thrombelastography. TXB2, 12-HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days p < 0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p < 0.001 as compared to baseline). Patients had negligible levels of TXB2 throughout, confirming a consistent therapeutic response to aspirin. There was a transient rise in thrombin-mediated clotting (MAThrombin at 48 hours p = 0.001 and 3 to 5 days p < 0.001) and a fall in AA- and ADP-induced clotting in the early post op period (both MAAA and MAADP p = 0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p = 0.008 for MAAA and p = 0.002 for MAADP), hence demonstrating a rebound effect. These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.

Detection of individual responses to clopidogrel: Validation of a novel, rapid analysis using thrombelastography 6s.

INTRODUCTION: There is potential value in testing individual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)-induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot amplitude (MA) in TEG 6s. METHODS: A total of 25 participants were included in whom ADP-induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel; (2) 12 patients with ACS given 600 mg of clopidogrel; (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All samples were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s. RESULTS: (1) TEG 5000 and TEG 6s both detected changes in ADP-induced platelet activation. Bland-Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R2  = 0.867, R = .936, P < .001), and the AUC15 result was available on average 13.3 minutes earlier. CONCLUSIONS: Thrombelastography 6s is a rapid, easy to use and accurate test of ADP-induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time-saving option for this test and has potential value in personalized P2Y12 inhibitor therapy.

High sensitivity troponin in the management of tachyarrhythmias.

BACKGROUND: The introduction of the highly sensitive troponin (hs-trop) assays into clinical practice has allowed for the more rapid diagnosis or exclusion of type 1 myocardial infarctions (T1MI) by clinicians, in addition type 2 myocardial infarctions (T2MI) are now more frequently detected. Tachyarrhythmias are one of the common causes of T2MI, the medium and long term outcome for this cohort of T2MI is yet to be clarified. METHODS: Retrospective review of consecutive patients admitted with a diagnosis of either (a) non ST-elevation myocardial infarction (NSTEMI) or (b) tachyarrhythmia was performed. Data were collected on patient demographics and investigations. Patient mortality status was recorded through the Personal Demographics Service (PDS) via NHS Digital. RESULTS: A total of 704 patients were eligible for inclusion to the study. 264 patients were included in the study with a final discharge diagnosis of NSTEMI and 440 patients with a final discharge diagnosis of tachyarrhythmia. There was a significantly higher peak troponin in NSTEMI patients compared to the tachyarrhythmia troponin positive group (4552ng/L vs 571ng/L, p<0.001). Mortality was significantly higher in the troponin positive tachyarrhythmia patients than the troponin negative patients (54 vs 34, 26.2% vs 14.5%, log rank p=0.003), furthermore, the mortality of NSTEMI and troponin positive tachyarrhythmia patients was similar (55 vs 54, 20.8% vs 26.2%, log rank p=0.416). Only one patient (0.14%) was given a formal diagnosis of T2MI. CONCLUSIONS: These data suggest that troponin positive tachyarrhythmia is not a benign diagnosis, and has a mortality rate similar to NSTEMI. Formal labeling as T2MI is rare in real life practice. More investigation into the detection and management of T2MI and troponin positive arrhythmia patients is now warranted.

High sensitivity troponins in contemporary cardiology practice: are we turning a corner?

INTRODUCTION: Troponin is considered to be the gold standard biomarker for ruling out MI. There has been a drive to improve the diagnostic speed, and as such the high sensitivity cardiac troponin (hs-cTn) assays have been introduced into clinical practice and are now part of international guidelines. Their novel value in clinical practice more generally is becoming apparent. Areas covered: In this review we will evaluate the evidence for the use of hs-cTn assays in clinical practice, the issues with the assay and how the hs-cTn can be utilized in the future as a biomarker of cardiovascular risk. Expert commentary: The use of the hs-cTn assays as a 'rule out' test for MI is compelling, as a 'rule in' there are significant issues relating the specificity of the assay for MI. The future of the assay may lie in population screening and risk modeling.

Does the evidence really suggest that we should completely revascularise bystander disease in patients with ST elevation myocardial infarction undergoing primary angioplasty? Why we still need more definitive trial data to change routine practice.

INTRODUCTION: There remains considerable heterogeneity in the management of significant lesions in non culprit coronary arteries in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Three recent randomised trials have shown clinical outcome benefit in a complete revascularisation approach when compared to PPCI of the culprit artery alone. By contrast, observational data suggest that an aggressive complete revascularisation may not confer clinical benefit and may, in some cases, be harmful. Areas covered: In this review we discuss the three recent randomised trials that have advocated a complete revasculariation approach in addition to data available from registries. Expert commentary: An adequately powered, randomised controlled trial is required to answer the question of whether complete revascularisation in STEMI patients is beneficial and, if so, whether it should be ischaemia directed and whether it should be at the index procedure or staged.

Is arachidonic acid stimulation really a test for the response to aspirin? Time to think again?

INTRODUCTION: Platelets play a key role in pathogenesis of atherothrombosis. Activated platelets initiate thrombus formation. Antiplatelet therapy (APT) modifies these properties. APT involves aspirin. The existence of 'aspirin resistance' is reported in many populations with cardiovascular disease. The prevalence of this phenomenon is highly variable, affecting more than 50% of patient subgroups in some papers. Areas covered: This review describes the prevalence of 'aspirin resistance', analyses why there is so much apparent variation and addresses whether the commonly used tests of aspirin response are in fact accurately assessing its functional performance. The clinical consequences if arachidonic acid(AA)-mediated assays do not accurately assess the functional performance of aspirin could be important. Expert commentary: Two important issues arise, firstly, that it can no longer be considered robust to use AA-induced platelet activation as a true diagnostic test of functional response to aspirin. It is clear that the output from PFT using AA as an agonist are not even a surrogate for the pharmacological activity of aspirin. Secondly, current data raise important and clinically relevant questions about, how AA stimulation induces clotting in individuals in whom aspirin is effective at its COX-1 target. The evidence indicates at least one recruitable, COX-1-independent pathway that is associated with vascular inflammation.

Stent Thrombosis Patients with Hyporesponsiveness to Clopidogrel, Prasugrel, and Ticagrelor: A Case Series Using Short Thromboelastography.

Patients after percutaneous coronary intervention (PCI) with stent implantation and functional hyporesponsiveness to P2Y12 inhibitors are at higher risk of ischaemic events, particularly stent thrombosis (ST). It is currently not routine practice to assess the functional response to these agents. However, concern over functional hyporesponsiveness to clopidogrel has led to widespread uptake of prasugrel and ticagrelor as the default P2Y12 inhibitor after stent implantation in patients with acute coronary syndrome. Here we report, for the first time, 3 cases in which patients who have had ST exhibit hyporesponsiveness to clopidogrel, prasugrel, and ticagrelor.

Is cardiac resynchronisation therapy feasible, safe and beneficial in the very elderly?

OBJECTIVE: To evaluate whether cardiac resynchronisation therapy (CRT) implantation was feasible and safe in octogenarians and the association with symptoms. METHODS: Consecutive patients undergoing CRT implantation were recruited from two UK centers. Patients grouped according to age: < 80 & ≥ 80 years. Baseline demographics, complications and outcomes were compared between those groups. RESULTS: A total of 439 patients were included in this study, of whom 26% were aged ≥ 80 years. Octogenarians more often received cardiac resynchronization therapy pacemaker in comparison to cardiac resynchronisation therapy-defibrillator. Upgrade from pacemaker was common in both groups (16% < 80 years vs. 22% ≥ 80 years, P = NS). Co-morbidities were similarly common in both groups (overall diabetes: 25%, atrial fibrillation: 23%, hypertension: 45%). More patient age ≥ 80 years had significant chronic kidney disease (CKD, estimated glomerular filtration rate < 45 mL/min per 1.73 m(2), 44% vs. 22%, P < 0.01). Overall complication rates (any) were similar in both groups (16% vs. 17%, P = NS). Both groups demonstrated symptomatic benefit. One-year mortality rates were almost four fold greater in octogenarians as compared with the younger cohort (13.9% vs. 3.7%, P < 0.01). CONCLUSIONS: CRT appears to be safe in the very elderly despite extensive co-morbidity, and in particular frequent severe CKD. Symptomatic improvement appears to be meaningful. Strategies to increase the appropriate identification of elderly patients with CHF who are potential candidates for CRT are required.

Clinical utility of biomarkers in chronic kidney disease and chronic heart failure.

Biomarkers have an increasingly important clinical role in managing patients with heart failure as well as those with kidney disease, both common conditions with generally poor prognostic outcomes and huge impacts on healthcare economics. For patients with chronic heart failure, biomarkers have become centre place in streamlining diagnostic pathways as well as identifying those with worse prognosis. There is much interest in the role for biomarkers in identifying patients at risk of acute kidney injury, although a number of these currently remain as research tools or are in the early stages of evaluation in clinical practice. Patients with cardiorenal syndrome represent a particular challenge to the clinician, and recent studies have suggested a valuable clinical role for certain biomarkers in this setting, either on their own or in combination. This paper will focus on biomarkers with a current clinical role in patients with cardiorenal disease (natriuretic peptides and neutrophil gelatinase-associated lipocalin), although brief reference will be made to other biomarkers with potential future application.