Nawzad Saleh

Effect of postconditioning on infarct size in patients with ST elevation myocardial infarction

Background Small studies suggest that postconditioning reperfusion interrupted by brief repetitive cycles of reocclusions, may protect the myocardium in the clinical setting. Objective To test the hypothesis that postconditioning limits infarct size in relation to the area at risk in patients with ST elevation myocardial infarction (STEMI). Methods 76 patients (aged 37–87 years) eligible for primary percutaneous coronary intervention due to STEMI were randomised to standard percutaneous coronary intervention (n=38) or postconditioning, consisting of four cycles of 60 s reperfusion and 60 s of reocclusion before permanent reperfusion (n=38). Results The area at risk was determined from angiographic abnormally contracting segments. Infarct size was quantified from delayed enhancement MRI on days 6–9. Infarct size, expressed in relation to the area at risk, did not differ between the control group (44%; 30, 56) (median and quartiles) and the post-conditioned group (47%; 23, 63). The slope of the regression lines relating infarct size to the area at risk differed between the two groups. Infarct size was significantly (p=0.001) reduced by postconditioning in patients with large areas at risk. The area under the curve and peak troponin T release and CKMB during 48 h did not differ between patients in the control and postconditioning groups. Conclusions This prospective, randomised trial suggests that postconditioning does not reduce infarct size in patients with STEMI in the overall study group. The data indicate that postconditioning may be of value in patients with large areas at risk. Clinical trial registration information Karolinska Clinical Trial Registration (http://www.kctr.se). Unique identifier: CT20080014.

Effect of remote ischemic conditioning on infarct size in patients with anterior ST-elevation myocardial infarction

BACKGROUND Previous studies indicate that remote ischemic conditioning performed before percutaneous coronary intervention (PCI) reduces infarct size in patients with ST-elevation myocardial infarction (STEMI). It remains unclear whether remote conditioning affords protection when performed in adjunct to primary PCI. We aimed to study whether remote ischemic per-postconditioning (RIperpostC) initiated after admission to the catheterization laboratory attenuates myocardial infarct size in patients with anterior STEMI. METHODS In this prospective multicenter trial 93 patients with anterior STEMI were randomized to RIperpostC or sham procedure as adjunct to primary PCI. RIperpostC was started on arrival in the catheterization laboratory by 5-minute cycles of inflation and deflation of a blood pressure cuff around the left thigh and continued throughout the PCI procedure. Infarct size and myocardium at risk were determined by cardiac magnetic resonance at day 4 to 7. The primary outcome was myocardial salvage index. RESULTS There was no significant difference in myocardial salvage index between the RIperpostC and control group (median 48.5% and interquartile range 30.9%-60.8% vs 49.2% [42.1%-58.8%]). Neither did absolute infarct size in relation to left ventricular myocardial volume differ significantly (RIperpostC 20.6% [14.1%-31.7%] vs control 17.9% [13.4%-25.0%]). The RIperpostC group had larger myocardial area at risk than the control group (43.1% (35.4%-49.7%) vs 37.0% (30.8%-44.1%) of the left ventricle, P=.03). Peak value and area under the curve for troponin T did not differ significantly between the study groups. CONCLUSIONS RIperpostC initiated after admission to the catheterization laboratory in patients with anterior STEMI did not confer protection against reperfusion injury.

C-reactive protein and myocardial infarction during percutaneous coronary intervention

Objective.  To evaluate the prognostic information of preprocedural C‐reactive protein (CRP) levels in serum to predict myocardial infarction during percutaneous coronary interventions (PCI).

Mortality and extent of coronary artery disease in 2776 patients with type 1 diabetes undergoing coronary angiography: A nationwide study

Background In a modern perspective there is limited information on mortality by affected coronary vessels assessed by coronary angiography in patients with type 1 diabetes. The aim of the present study was to characterise distribution of coronary artery disease and impact on long-term mortality in patients with type 1 diabetes undergoing coronary angiography. Design The design of this research was a nationwide population-based cohort study. Methods Individuals (n = 2776) with type 1 diabetes undergoing coronary angiography 2001–2013 included in the Swedish National Diabetes Registry and Swedish Coronary Angiography and Angioplasty Registry were followed for mortality until 31 December 2013 (mean 7.1 years). In 79% the indication was stable or acute coronary artery disease. Coronary artery disease was categorised into normal (21%), one- (23%), two- (18%), three- (29%) and left main-vessel disease (8%). Results Mean age was 57 years and 58% were male. Mean diabetes duration was 35 years, glycated haemoglobin was 67 mmol/mol and 44% had normal or one-vessel disease. In multivariate Cox proportional analyses hazard ratio for mortality compared with normal findings was 1.09 (95% confidence interval 0.80–1.48) for one, 1.43 (1.05–1.94) for two, 1.47 (1.10–1.96) for three and 1.90 (1.35–2.68) for left main-vessel disease. Renal failure 2.29 (1.77–2.96) and previous heart failure 1.76 (1.46–2.13) were highly associated with mortality. Standard mortality ratio the first year was 5.55 (4.65–6.56) and decreased to 2.80 (2.18–3.54) after five years. Conclusions In patients with type 1 diabetes referred for coronary angiography mortality is influenced by numbers of affected coronary vessels. The overall mortality rate was higher compared with the general population. These results support early intensive prevention of coronary artery disease in this population.

Impact of percutaneous femoral arteriotomy closure using the MANTATM device on vascular and bleeding complications after transcatheter aortic valve replacement

To evaluate the feasibility of fully percutaneous closure using a novel collagen‐based vascular closure device after transfemoral aortic valve replacement (TAVR).

The obesity paradox: An analysis of pre-procedure weight trajectory on survival outcomes in patients undergoing transcatheter aortic valve implantation

INTRODUCTION Increased mortality has been observed in those with cardiovascular diseases who are of normal body mass index (BMI) compared to the overweight and the obese. A similar association has been demonstrated in patients undergoing transcatheter aortic valve (TAVI) implantation. However, it still remains unclear whether low or normal BMI itself is unfavourable or whether this is merely a reflection of cardiac cachexia due to severe aortic stenosis. The hypothesis for the study was that weight change prior to TAVI may be associated with increased mortality following the procedure. SUBJECTS, MATERIALS AND METHODS Single centre retrospective analysis using the SWEDEHEART registry, national mortality statistics and local hospital database. Body mass index was used as the anthropomorphic measurement and patients grouped by WHO categories and weight change trajectory before and at TAVI. Kaplan-Meier survival was constructed and a Cox proportional hazard model used to evaluate predictors of outcome. RESULTS Consecutive data on 493 patients with three year follow-up between 2008-2015 were evaluated. Overweight and obese body mass index categories (BMI>25) were associated with improved mortality compared to normal and underweight patients (BMI<25) (log rank p=0.02), hazard ratio of 0.68 (0.50-0.93). Weight loss trajectory was associated with increased mortality compared to stable weight (log rank p=0.01), hazard ratio 1.64 p=0.025. CONCLUSION The pre-procedural weight trajectory of patients undergoing TAVI is an important predictor of clinical outcome after TAVI. Patients with stable weight trajectories are associated with improved mortality outcome compared to those with decreasing weight.

Relevance of genetic polymorphisms in inflammatory response to percutaneous coronary intervention

Abstract It has recently been reported that inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), increase in plasma as a response to the stimulus of percutaneous coronary intervention (PCI). The magnitude of this inflammatory response is associated with the risk of restenosis. There is a large inter-individual variation in the inflammatory response to PCI. One factor shown to be of importance is stent implantation but the reasons for the variation are to a large extent unknown. One possible reason could be genetic variation in the regulation of CRP and IL-6 levels. One functional single nucleotide polymorphism (SNP) located at position -286 in the promoter region of the CRP gene associated with plasma CRP levels has recently been described. Another SNP located at -174 in the promoter region of the IL-6 gene has been associated with plasma IL-6 concentration. The hypothesis behind the present study was that the SNPs CRP -286 and IL-6 -174 were associated with the inflammatory response to PCI, including stent implantation. The results did not show any association with plasma levels of CRP and IL-6 measured as area-under-curve up to 72 hours after PCI indicating that genetic variation is unlikely to play a major role for the inflammatory response to PCI.

Characteristics and Prognosis in Women and Men With Type 1 Diabetes Undergoing Coronary Angiography: A Nationwide Registry Report

OBJECTIVE To describe sex aspects on extent of coronary artery disease (CAD) and prognosis in a contemporary population with type 1 diabetes. RESEARCH DESIGN AND METHODS All patients undergoing coronary angiography, 2001–2013, included in the Swedish Coronary Angiography and Angioplasty Registry and the Swedish National Diabetes Register as type 1 diabetes were followed for mortality until 31 December 2013. The coronary angiogram was classified into normal, one-vessel disease, two-vessel disease, three-vessel disease, and left main stem disease. RESULTS In all, 2,776 patients (42% women) with mean age 58 years (SD 11) were followed for 7.2 years (SD 2.2). Diabetes duration was longer in women (37 ± 14 vs. 34 ± 14 years in men; P < 0.001), who also had more retinopathy (68% vs. 65%; P = 0.050), whereas microalbuminuria was less common (41% vs. 51%; P < 0.001). Indications for coronary angiography did not substantially differ in women and men. The extent of CAD was somewhat less severe in women (normal angiogram 23.5% vs. 19.1%, three-vessel and left main stem disease 34.5% vs. 40.4%; P = 0.002), whereas mortality did not differ (adjusted hazard ratio 1.03 [95% CI 0.88–1.20]; P = 0.754). The standard mortality ratio for women the first year was 7.49 (5.73–9.62) and for men was 4.58 (3.60–5.74). CONCLUSIONS In patients with type 1 diabetes admitted for coronary angiography, the extent of CAD was almost similar in women and men, and total long-term mortality did not differ. Type 1 diabetes was associated with higher mortality risk in women than in men when compared with the general population. These data support that type 1 diabetes attenuates the cardiovascular risk difference seen in men and women in the general population.

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

BACKGROUND Remote ischemic conditioning (RIC), i.e. short cycles of ischemia and reperfusion in remote tissue, is a novel approach to protect against myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction. The nature of the factors transmitting the protective effect of RIC remains unknown, and both neuronal and hormonal mechanisms appear to be involved. A recent study indicated involvement of glucagon-like peptide-1 (GLP-1) regulated by the vagal nerve in RIC in rats. In the present study we aimed to investigate whether the protective effect of RIC is mediated by a GLP-1 receptor-dependent mechanism in humans. METHODS Endothelial function was determined from flow-mediated dilatation (FMD) of the brachial artery before and after 20 min of forearm ischemia and 20 min of reperfusion in twelve healthy subjects on three occasions: (A) ischemia-reperfusion without intervention, (B) ischemia-reperfusion + RIC and (C) iv administration of the GLP-1 receptor antagonist exendin(9-39) + ischemia-reperfusion + RIC. RESULTS Ischemia-reperfusion reduced FMD from 4.7 ± 0.8% at baseline to 1.5 ± 0.4% (p < 0.01). RIC protected from the impairment in FMD induced by ischemia-reperfusion (4.6 ± 1.1% at baseline vs. 5.0 ± 1.1% following ischemia-reperfusion). Exendin(9-39) abolished the protection induced by RIC (FMD 4.9 ± 0.9% at baseline vs. 1.4 ± 1.3% following ischemia-reperfusion; p < 0.01) but did not affect basal FMD. Plasma GLP-1 levels did not change significantly between examinations. CONCLUSION The present study is the first to suggest that RIC protects against endothelial ischemia-reperfusion injury via a GLP-1 receptor-mediated mechanism in humans.

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

BackgroundClinical 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.MethodsRetrospective 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.ResultsMaR 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%.ConclusionQuantification 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 registrationClinical trial registration information for the parent clinical trial:Karolinska Clinical Trial Registration (2008)Unique identifier: CT20080014. Registered 04th January 2008