Remote ischemic conditioning to protect the heart in myocardial infarction : therapeutic intervention and underlying mechanisms

Background Urgent reperfusion of the occluded coronary artery halts the ischemic insult to the myocardium and is the single most important action to limit infarct size in ST-elevation myocardial infarction. However, reperfusion itself introduces an additional threat to the recovering ischemic myocardium whereby still viable cardiomyocytes suffer additional irreversible damage. This is referred to as reperfusion injury and significantly contributes to final infarct size. As of yet there is no established treatment to avoid or limit reperfusion injury, but promising results have been presented from early clinical trials of remote ischemic conditioning, whereby short cycles of non-harmful ischemia and reperfusion performed in remote tissue during the late stages of myocardial ischemia or early stages of myocardial reperfusion elicits an innate mechanism that ultimately terminates in cardioprotection. However, the exact underlying mechanisms are not fully known and additional clinical trials are needed to decide the possible role for remote ischemic conditioning in the treatment of patients with ST-elevation myocardial infarction. This thesis was undertaken to determine the effects of remote ischemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction and to explore underlying mechanisms. Studies I and II The effect of remote ischemic conditioning performed during the late stages of ischemia and at reperfusion as an adjunct to primary percutaneous intervention was investigated in 115 patients with anterior ST-elevation myocardial infarction. Infarct size as evaluated by cardiac magnetic resonance imaging during the first week and six months after the myocardial infarction, as well as clinical outcomes up to three years of follow-up were not affected by remote ischemic conditioning. Study III The involvement of the glucagon-like peptide-1 receptor in the signaling pathway of remote ischemic conditioning was explored in twelve healthy males. Intravenous infusion of the glucagon-like peptide-1 receptor antagonist exendin(9-39) abolished the protection against endothelial ischemia-reperfusion injury provided by remote ischemic conditioning, as evaluated by ultrasound based measurement of flow mediated dilatation in the brachial artery. Study IV The effect of chronic ticagrelor treatment on endothelial function was evaluated in twenty male patients with a previous acute coronary syndrome. Chronic ticagrelor treatment was not associated with protection against endothelial ischemia-reperfusion injury or better basal endothelial function compared to after its discontinuation, as evaluated by ultrasound based measurement of flow mediated dilatation in the brachial artery. Conclusions Remote ischemic conditioning performed during the late stages of ischemia and at reperfusion as an adjunct to primary percutaneous coronary intervention in patients with anterior STelevation myocardial infarction does not lead to smaller myocardial infarct size or improved clinical outcomes. Remote ischemic conditioning utilizes a glucagon-like peptide-1 receptor dependent pathway to protect against endothelial ischemia-reperfusion injury. Chronic ticagrelor treatment does not provide protection against endothelial ischemia-reperfusion injury or improved basal endothelial function compared to after its discontinuation

Same-day discharge after percutaneous closure of persistent foramen ovale using intracardiac echocardiography and the Gore Septal Occluder

AimPeriprocedural and postinterventional care of patients undergoing closure of patent foramen ovale (PFO) varies significantly across care providers. Same-day discharge (SDD) after transcatheter interventions is an evolving concept. This study aimed to assess the same-day discharge rate and incidence of complications in patients undergoing PFO closure with intracardiac echocardiography (ICE) using the Gore®Cardioform Septal Occluder (GSO) device. The secondary aim was to analyse the efficacy of femoral vein closure with Perclose ProGlide.MethodsPatients who underwent PFO closure with the GSO device at a university hospital in Stockholm, Sweden, were retrospectively included between March 1, 2017, and June 30, 2020, all with cryptogenic stroke as the indication for the procedure. All patients underwent PFO closure with conscious sedation and local anaesthesia. The indication for all patients was a cryptogenic stroke. Periprocedural imaging was performed using ICE and fluoroscopy in all patients. Patient characteristics and periprocedural data were collected from patient charts. Patients were kept on bed rest for 4–6 h post-intervention. Transthoracic echocardiography and clinical examination, including groin status, were performed before discharge. No clinical routine follow-up was performed the day following the intervention. Clinical follow-up was done by phone call two weeks after the procedure, and echocardiographic follow-up was done after 12 months. Data were analysed using linear and logistic regression models.ResultsIn total, 262 patients were included, of which 246 (94%) had SDD. 166 patients (63%) received the ProGlide™ system for femoral vein access closure. Post-procedural arrhythmias occurred in 17 (6%) patients, and vascular complications in 9 patients (3%). The overall closure rate at follow-up was 98.5%. 25 out of 264 patients (9.5%) had to be readmitted within the first eight weeks after PFO closure, 16 due to atrial fibrillation warranting electric cardioversion, one due to an arteriovenous fistula that was operated, four due to chest pain/pain at the access site, and four patients developed fever. There was no difference in SDD among patients who received ProGlide™ vs. patients who did not receive ProGlide™.ConclusionSDD appears safe after transcatheter PFO closure with the GSO device with high procedural success rates. Low rates of complications and readmissions make the intervention suitable for this patient-friendly and cost-effective concept

Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury. During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic - however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial ischaemia/reperfusion injury

Quantification of myocardium at risk in ST- elevation myocardial infarction: a comparison of contrast-enhanced steady-state free precession cine cardiovascular magnetic resonance with coronary angiographic jeopardy scores

Abstract Background Clinical outcome following acute myocardial infarction is predicted by final infarct size evaluated in relation to left ventricular myocardium at risk (MaR). Contrast-enhanced steady-state free precession (CE-SSFP) cardiovascular magnetic resonance imaging (CMR) is not widely used for assessing MaR. Evidence of its utility compared to traditional assessment methods and as a surrogate for clinical outcome is needed. Methods Retrospective analysis within a study evaluating post-conditioning during ST elevation myocardial infarction (STEMI) treated with coronary intervention (n = 78). CE-SSFP post-infarction was compared with angiographic jeopardy methods. Differences and variability between CMR and angiographic methods using Bland-Altman analyses were evaluated. Clinical outcomes were compared to MaR and extent of infarction. Results MaR showed correlation between CE-SSFP, and both BARI and APPROACH scores of 0.83 (p < 0.0001) and 0.84 (p < 0.0001) respectively. Bias between CE-SSFP and BARI was 1.1% (agreement limits -11.4 to +9.1). Bias between CE-SSFP and APPROACH was 1.2% (agreement limits -13 to +10.5). Inter-observer variability for the BARI score was 0.56 ± 2.9; 0.42 ± 2.1 for the APPROACH score; -1.4 ± 3.1% for CE-SSFP. Intra-observer variability was 0.15 ± 1.85 for the BARI score; for the APPROACH score 0.19 ± 1.6; and for CE-SSFP -0.58 ± 2.9%. Conclusion Quantification of MaR with CE-SSFP imaging following STEMI shows high correlation and low bias compared with angiographic scoring and supports its use as a reliable and practical method to determine myocardial salvage in this patient population. Trial registration Clinical trial registration information for the parent clinical trial: Karolinska Clinical Trial Registration (2008) Unique identifier: CT20080014. Registered 04th January 200

Agreement between physiotherapists rating scapular posture in multiple planes in patients with neck pain: Reliability study

Objective Evaluation of scapular posture is an integral component of the clinical assessment of painful neck disorders. The aim of this study was to evaluate agreement between therapist judgements of scapula posture in multiple biomechanical planes in individuals with neck pain. Design Inter-therapist reliability study. Setting Research laboratory. Participants Fifteen participants with chronic neck pain. Main outcome measures Four physiotherapists recorded ratings of scapular orientation (relative to the thorax) in five different scapula postural planes (plane of scapula, sagittal plane, transverse plane, horizontal plane, and vertical plane) under four test conditions (at rest, and during three isometric shoulder conditions) in all participants. Inter-therapist reliability was expressed using both generalized and paired kappa coefficient. Results Following adjustment for expected agreement and the high prevalence of neutral ratings (81%), on average both the generalised kappa (0.37) as well as Cohen's Kappa for the two therapist pairs (0.45 and 0.42) demonstrated only slight to moderate inter-therapist reliability. Conclusions The findings suggest that ratings of scapular posture in individuals with neck pain by visual inspection has only slight to moderate reliability and should only be used in conjunction with other clinical tests when judging scapula function in these patients

Mind the Gap in TAVR

Misloading during transcatheter aortic valve replacement (TAVR) is rare but can cause unpredictable valve release if unrecognized. We describe how to identify a misloaded ACURATE neo2 device, and 3 methods to solve this by using a modified technique of valve deployment, ipsilateral extraction, and contralateral valve externalization with extracorporeal valve release

Oxygen therapy in ST-elevationmyocardial infarction

Aims To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes. Methods and results The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days. Conclusions Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis