European heart journal open最新文献

{"title":"The use of venoarterial extracorporeal membrane oxygenation in cardiogenic shock: a narrative review.","authors":"Tara Gédéon, Tetiana Zolotarova, Mark J Eisenberg","doi":"10.1093/ehjopen/oeae051","DOIUrl":"10.1093/ehjopen/oeae051","url":null,"abstract":"<p><strong>Aims: </strong>Cardiogenic shock (CS) develops in up to 10% of patients with acute myocardial infarction (AMI) and carries a 50% risk of mortality. Despite the paucity of evidence regarding its benefits, venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in clinical practice in patients with AMI in CS (AMI-CS). This review aims to provide an in-depth description of the four available randomized controlled trials to date designed to evaluate the benefit of VA-ECMO in patients with AMI-CS.</p><p><strong>Methods and results: </strong>The literature search was conducted on PubMed, Google Scholar, and clinicaltrials.gov to identify the four relevant randomized control trials from years of inception to October 2023. Despite differences in patient selection, nuances in trial conduction, and variability in trial endpoints, all four trials (ECLS-SHOCK I, ECMO-CS, EUROSHOCK, and ECLS-SHOCK) failed to demonstrate a mortality benefit with the use of VA-ECMO in AMI-CS, with high rates of device-related complications. However, the outcome of these trials is nuanced by the limitations of each study that include small sample sizes, challenging patient selection, and high cross-over rates to the intervention group, and lack of use of left ventricular unloading strategies.</p><p><strong>Conclusion: </strong>The presented literature of VA-ECMO in CS does not support its routine use in clinical practice. We have yet to identify which subset of patients would benefit most from this intervention. This review emphasizes the need for designing adequately powered trials to properly assess the role of VA-ECMO in AMI-CS, in order to build evidence for best practices.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"4 4","pages":"oeae051"},"PeriodicalIF":0.0,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of pulsed field ablation compared to cryoballoon ablation in the treatment of atrial fibrillation: a meta-analysis.","authors":"Isabel Rudolph, Giulio Mastella, Isabell Bernlochner, Alexander Steger, Gesa von Olshausen, Franziska Hahn, Reza Wakili, Karl-Ludwig Laugwitz, Eimo Martens, Manuel Rattka","doi":"10.1093/ehjopen/oeae044","DOIUrl":"10.1093/ehjopen/oeae044","url":null,"abstract":"<p><strong>Aims: </strong>Pulmonary vein isolation (PVI) represents the gold standard in the treatment of atrial fibrillation (AF) and the use of single-shot techniques, such as cryoballoon ablation (CBA) and pulsed field ablation (PFA) using a pentaspline catheter, has gained prominence. Recent studies hypothesize that PFA might be superior to CBA, although procedural efficacy and safety data are inconsistent. A meta-analysis was conducted to compare both energy sources for the treatment of AF.</p><p><strong>Methods and results: </strong>A structured systematic database search and meta-analysis were performed on studies investigating outcomes, periprocedural complications, and/or procedural parameters of AF patients treated by either CBA or PFA. Eleven studies reporting data from 3805 patients were included. Pulmonary vein isolation by PFA was associated with a significantly lower recurrence of atrial fibrillation/atrial tachycardia [odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.54-0.98, I² = 20%] and fewer periprocedural complications (OR = 0.62, 95% CI = 0.40-0.96, I² = 6%) compared to CBA. The lower complication rate following PFA was mainly driven by fewer phrenic nerve injuries (OR = 0.19, 95% CI = 0.08-0.43, I² = 0%). However, there were more cases of cardiac tamponades after PFA (OR = 2.56, 95% CI = 1.01-6.49, I² = 0%). Additionally, using PFA for PVI was associated with shorter total procedure times [mean difference (MD) = -9.68, 95% CI = -14.92 to -4.43 min, I² = 92%] and lower radiation exposure (MD = -148.07, 95% CI = -276.50 to -19.64 µGy·mI² = 7%).</p><p><strong>Conclusion: </strong>Our results suggest that PFA for PVI, compared to CBA, enables shorter procedure times with lower arrhythmia recurrence and a reduced risk of periprocedural complications. Randomized controlled trials need to confirm our findings.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"4 3","pages":"oeae044"},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the 2022 pulmonary hypertension definition on haemodynamic classification and mortality in patients with aortic stenosis undergoing valve replacement.","authors":"Micha T Maeder, Lukas Weber, Susanne Pohle, Joannis Chronis, Florent Baty, Johannes Rigger, Martin Brutsche, Philipp Haager, Hans Rickli, Roman Brenner","doi":"10.1093/ehjopen/oeae037","DOIUrl":"10.1093/ehjopen/oeae037","url":null,"abstract":"<p><strong>Aims: </strong>With the 2022 pulmonary hypertension (PH) definition, the mean pulmonary artery pressure (mPAP) threshold for any PH was lowered from ≥25 to >20 mmHg, and the pulmonary vascular resistance (PVR) value to differentiate between isolated post-capillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH) was reduced from >3 Wood units (WU) to >2 WU. We assessed the impact of this change in the PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR).</p><p><strong>Methods and results: </strong>Severe AS patients (<i>n</i> = 503) undergoing pre-AVR cardiac heart catheterization were classified according to both the 2015 and 2022 definitions. The post-AVR mortality [median follow-up 1348 (interquartile range 948-1885) days] was assessed. According to the 2015 definition, 219 (44% of the entire population) patients had PH: 63 (29%) CpcPH, 125 (57%) IpcPH, and 31 (14%) pre-capillary PH. According to the 2022 definition, 321 (+47%) patients were diagnosed with PH, and 156 patients (31%) were re-classified: 26 patients from no PH to IpcPH, 38 from no PH to pre-capillary PH, 38 from no PH to unclassified PH, 4 from pre-capillary PH to unclassified PH, and 50 from IpcPH to CpcPH (CpcPH: +79%). With both definitions, only the CpcPH patients displayed increased mortality (hazard ratios ≈ 4). Among the PH-defining haemodynamic components, PVR was the strongest predictor of death.</p><p><strong>Conclusion: </strong>In severe AS, the application of the 2022 PH definition results in a substantially higher number of patients with any PH as well as CpcPH. With either definition, CpcPH patients have a significantly increased post-AVR mortality.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"4 3","pages":"oeae037"},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant targets.","authors":"Eloi Gagnon, Arnaud Girard, Jérôme Bourgault, Erik Abner, Dipender Gill, Sébastien Thériault, Marie-Claude Vohl, André Tchernof, Tõnu Esko, Patrick Mathieu, Benoit J Arsenault","doi":"10.1093/ehjopen/oeae043","DOIUrl":"10.1093/ehjopen/oeae043","url":null,"abstract":"<p><strong>Aims: </strong>Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed.</p><p><strong>Methods and results: </strong>To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, <i>P</i> = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, <i>P</i> = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, <i>P</i> = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, <i>P</i> = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, <i>P</i> = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, <i>P</i> = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses.</p><p><strong>Conclusion: </strong>These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"4 3","pages":"oeae043"},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaping tomorrow's vascular landscape with extracellular matrix stents.","authors":"Michael James, Viren S Sehgal","doi":"10.1093/ehjopen/oeae042","DOIUrl":"10.1093/ehjopen/oeae042","url":null,"abstract":"","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"4 3","pages":"oeae042"},"PeriodicalIF":0.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic value of left ventricular layer strain and specific regional strain patterns in cardiac amyloidosis and Fabry disease","authors":"Tilman Steudel, Gina Barzen, D. Frumkin, Elena Romero-Dorta, Sebastian Spethmann, Gerhard Hindricks, Karl Stangl, Fabian Knebel, Bettina Heidecker, Sima Canaan-Kühl, Helena Franziska Pernice, K. Hahn, I. Mattig, Anna Brand","doi":"10.1093/ehjopen/oeae041","DOIUrl":"https://doi.org/10.1093/ehjopen/oeae041","url":null,"abstract":"\u0000 \u0000 \u0000 Layer-specific left ventricular (LV) strain alterations have been suggested as a specific finding in Fabry Disease (FD). Our study aimed to assess the diagnostic value of layer specific radial strain (RS) indices compared to the established LV regional strain pattern in Cardiac Amyloidosis (CA) and FD, i.e. apical sparing, and posterolateral strain deficiency.\u0000 \u0000 \u0000 \u0000 We retrospectively analyzed the global, subendocardial, subepicardial LV radial strain, the corresponding strain gradient, as well as the regional and global longitudinal strain. The diagnostic accuracy of the diverse LV strain analyses was comparatively assessed using receiver operating curve (ROC) and multivariable regression analyses. In 40 FD and 76 CA patients, CA featured more reduced layer strain values [Global RS -12.3 (-15.6 to -9.6) in CA vs. -16.7 (-20.0 to-13.6) in FD; p < 0.001; subendocardial RS -22.3 (-27.4 to -15.9) vs. -28.3 (-31.8 to -23.6), p < 0.001; subepicardial RS -6.6 (-8.6 to -4.7) in CA vs. -8.9 (-11.7 to- 6.5 in FD; p < 0.001]. Global radial and longitudinal strain held an AUC of 0.75 (0.66 to 0.84) and AUC 0.73 (0.63 to 0.83). While the apical sparing and PLSD strain pattern showed the highest accuracy as single parameters [AUC 0.87 (0.79 to 0.95) and 0.81 (0.72 to 0.89), p < 0.001], the combination of subendocardial RS and the apical sparing pattern featured the highest diagnostic accuracy [AUC 0.92 (0.87 to 0.97)].\u0000 \u0000 \u0000 \u0000 Combining radial strain derived parameters to the established strain pattern apical sparing and PLSD improve the diagnostic accuracy in the echocardiographic assessment in suspected storage disease.\u0000","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141112450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Pressure Wave Components for Aortic Stiffness Monitoring through Spectral Regression Learning","authors":"Arian Aghilinejad, Morteza Gharib","doi":"10.1093/ehjopen/oeae040","DOIUrl":"https://doi.org/10.1093/ehjopen/oeae040","url":null,"abstract":"\u0000 \u0000 \u0000 The aging process notably induces structural changes in the arterial system, primarily manifesting as increased aortic stiffness, a precursor to cardiovascular events. While wave separation analysis is a robust tool for decomposing the components of blood pressure waveform, its relationship with cardiovascular events, such as aortic stiffening, is incompletely understood. Furthermore, its applicability has been limited due to the need for concurrent measurements of pressure and flow. Our aim in this study addresses this gap by introducing a spectral regression learning method for pressure-only wave separation analysis.\u0000 \u0000 \u0000 \u0000 Leveraging data from the Framingham Heart Study (2,640 individuals, 55% women), we evaluate the accuracy of pressure-only estimates, their interchangeability with reference method based on ultrasound-derived flow waves, and their association with Carotid-femoral pulse wave velocity. Method-derived estimates are strongly correlated with the reference ones for forward wave amplitude (R2=0.91), backward wave amplitude (R2=0.88), reflection index (R2=0.87), and moderately correlated with time delay between forward and backward waves (R2=0.38). The proposed pressure-only method shows interchangeability with reference method through covariate analysis. Adjusting for age, sex, body size, mean blood pressure, and heart rate, results suggest that both pressure-only and pressure-flow evaluations of wave separation parameters yield similar model performance for predicting Carotid-femoral pulse wave velocity with forward wave amplitude as the only significant factor (p < 0.001; 95% confidence interval, 0.056-0.097).\u0000 \u0000 \u0000 \u0000 We propose an interchangeable pressure-only wave separation analysis method and demonstrate its clinical applicability in capturing aortic stiffening. The proposed method provides valuable non-invasive tool for assessing cardiovascular health.\u0000","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"27 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141118163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific cardiac magnetic resonance pulmonary capillary wedge pressure.","authors":"Pankaj Garg, Ciaran Grafton-Clarke, Gareth Matthews, Peter Swoboda, Liang Zhong, Nay Aung, Ross Thomson, Samer Alabed, Ahmet Demirkiran, Vassilios S Vassiliou, Andrew J Swift","doi":"10.1093/ehjopen/oeae038","DOIUrl":"10.1093/ehjopen/oeae038","url":null,"abstract":"<p><strong>Aims: </strong>Heart failure (HF) with preserved ejection fraction disproportionately affects women. There are no validated sex-specific tools for HF diagnosis despite widely reported differences in cardiac structure. This study investigates whether sex, as assigned at birth, influences cardiac magnetic resonance (CMR) assessment of left ventricular filling pressure (LVFP), a hallmark of HF agnostic to ejection fraction.</p><p><strong>Methods and results: </strong>A derivation cohort of patients with suspected pulmonary hypertension and HF from the Sheffield centre underwent invasive right heart catheterization and CMR within 24 h of each other. A sex-specific CMR model to estimate LVFP, measured as pulmonary capillary wedge pressure (PCWP), was developed using multivariable regression. A validation cohort of patients with confirmed HF from the Leeds centre was used to evaluate for the primary endpoints of HF hospitalization and major adverse cardiovascular events (MACEs). Comparison between generic and sex-specific CMR-derived PCWP was undertaken. A total of 835 (60% female) and 454 (36% female) patients were recruited into the derivation and validation cohorts respectively. A sex-specific model incorporating left atrial volume and left ventricular mass was created. The generic CMR PCWP showed significant differences between males and females (14.7 ± 4 vs. 13 ± 3.0 mmHg, <i>P</i> > 0.001), not present with the sex-specific CMR PCWP (14.1 ± 3 vs. 13.8 mmHg, <i>P</i> = 0.3). The sex-specific, but not the generic, CMR PCWP was associated with HF hospitalization (hazard ratio 3.9, <i>P</i> = 0.0002) and MACE (hazard ratio 2.5, <i>P</i> = 0.001) over a mean follow-up period of 2.4 ± 1.2 years.</p><p><strong>Conclusion: </strong>Accounting for sex improves precision and prognostic performance of CMR biomarkers for HF.</p>","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"4 3","pages":"oeae038"},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medical treatment of heart failure with RAS inhibitors and beta blockers in aortic stenosis – association to long-term outcome after aortic valve replacement","authors":"Johan Hopfgarten, Stefan James, L. Lindhagen, T. Baron, Elisabeth Ståhle, C. Christersson","doi":"10.1093/ehjopen/oeae039","DOIUrl":"https://doi.org/10.1093/ehjopen/oeae039","url":null,"abstract":"\u0000 \u0000 \u0000 There is a lack of robust data on optimal medical treatment of heart failure in patients with severe aortic stenosis, with no randomized controlled trials guiding treatment.\u0000 \u0000 \u0000 \u0000 To study the association between exposure to renin-angiotensin-aldosterone system (RAS) inhibitors or beta-blockers and outcome after aortic valve replacement in patients with aortic stenosis and heart failure.\u0000 \u0000 \u0000 \u0000 The study included all patients with heart failure undergoing aortic valve replacement for aortic stenosis in Sweden between 2008-2016 (n = 4668 patients). Exposure to treatment was assessed by continuous tracking of drug dispensations and outcome events were all-cause mortality and hospitalization for heart failure collected from national patient registries. After adjustment for age, sex, atrial fibrillation, hypertension, diabetes mellitus and prior myocardial infarction Cox regression analysis showed that RAS inhibition was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.58, 95% CI 0.51 - 0.65) and preserved LV-EF (HR 0.69, 95% CI 0.56 - 0.85). Beta-blockade was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.81, 95% CI 0.71–0.92), but not in preserved LV-EF (HR 0.87, 95% CI 0.69 - 1.10). There was no association between RAS inhibition or beta-blockade and the risk of hospitalization for heart failure.\u0000 \u0000 \u0000 \u0000 RAS inhibition was associated with lower all-cause mortality after valve replacement in patients with both reduced and preserved LV-EF. Beta-blockade was associated with lower all-cause mortality only in patients with reduced LV-EF.\u0000","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":" 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140994580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Expression and Ultrastructural Evidence for Metabolic Derangement in the Primary Mitral Regurgitation Heart","authors":"Mariame Selma Kane, J. X. M. Juncos, S. Manzoor, Maximiliano Grenett, Joo-Yeun Oh, Betty Pat, Mustafa I Ahmed, Clifton Lewis, James E Davies, Thomas S. Denney, Jonathan McConathy, Louis J. Dell'Italia","doi":"10.1093/ehjopen/oeae034","DOIUrl":"https://doi.org/10.1093/ehjopen/oeae034","url":null,"abstract":"\u0000 \u0000 \u0000 Chronic neurohormonal activation and hemodynamic load cause derangement in myocardial substrate utilization. We test the hypothesis that the primary mitral regurgitation heart (PMR) heart shows altered metabolic gene profile and cardiac ultrastructure consistent with decreased fatty acid and glucose metabolism despite LVEF > 60%.\u0000 \u0000 \u0000 \u0000 Metabolic gene expression in right atrial (RA), left atrial (LA), and left ventricular (LV) biopsies from donor hearts (n = 10) and from patients with moderate to severe PMR (n = 11) at surgery showed decreased mRNA glucose transporter type 4 (GLUT-4), GLUT-1 and insulin receptor substrate 2 and increased mRNA hexokinase 2, O-linked N-acetylglucosamine transferase and O-GlcNAcase, rate-limiting steps in the hexosamine biosynthetic pathway. Pericardial fluid levels of Neuropeptide Y were 4-fold higher than simultaneous plasma indicative of increased sympathetic drive. Quantitative TEM shows glycogen accumulation, glycophagy, increased lipid droplets, and mitochondrial cristae lysis. These findings are associated with increased mRNA for glycogen synthase kinase 3β, decreased carnitine palmitoyl transferase 2, and fatty acid synthase in PMR vs. normals. Cardiac magnetic resonance/positron emission tomography for 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake showed decreased LV [18F]FDG uptake and increased plasma HbA1c, free fatty acids, mtDAMPs in a separate cohort of stable moderate PMR patients with LVEF > 60% (n = 8) vs. normal controls (n = 8).\u0000 \u0000 \u0000 \u0000 The PMR heart has a global ultrastructural and metabolic gene expression pattern of decreased glucose uptake along with increased glycogen and lipid droplets. Further studies must determine whether this presentation is an adaptation or maladaptation in the PMR heart in the clinical evaluation of PMR.\u0000","PeriodicalId":93995,"journal":{"name":"European heart journal open","volume":"181 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141050159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}