The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Ryanodine Receptor Glycation Favors Mitochondrial Damage in the Senescent Heart.

BACKGROUND: Senescent cardiomyocytes exhibit a mismatch between energy demand and supply that facilitates their transition toward failing cells. Altered calcium transfer from sarcoplasmic reticulum (SR) to mitochondria has been causally linked to the pathophysiology of aging and heart failure. METHODS: Because advanced glycation-end products accumulate throughout life, we investigated whether intracellular glycation occurs in aged cardiomyocytes and its impact on SR and mitochondria. RESULTS: Quantitative proteomics, Western blot and immunofluorescence demonstrated a significant increase in advanced glycation-end product-modified proteins in the myocardium of old mice (≥20months) compared with young ones (4-6months). Glyoxalase-1 activity (responsible for detoxification of dicarbonyl intermediates) and its cofactor glutathione were decreased in aged hearts. Immunolabeling and proximity ligation assay identified the ryanodine receptor (RyR2) in the SR as prominent target of glycation in aged mice, and the sites of glycation were characterized by quantitative mass spectrometry. RyR2 glycation was associated with more pronounced calcium leak, determined by confocal microscopy in cardiomyocytes and SR vesicles. Interfibrillar mitochondria-directly exposed to SR calcium release-from aged mice had increased calcium content compared with those from young ones. Higher levels of advanced glycation-end products and reduced glyoxalase-1 activity and glutathione were also present in atrial appendages from surgical patients ≥75 years as compared with the younger ones. Elderly patients also exhibited RyR2 hyperglycation and increased mitochondrial calcium content that was associated with reduced myocardial aerobic capacity (mitochondrial O2 consumption/g) attributable to less respiring mitochondria. In contracting HL-1 cardiomyocytes, pharmacological glyoxalase-1 inhibition recapitulated RyR2 glycation and defective SR-mitochondria calcium exchange of aging. CONCLUSIONS: Mitochondria from aging hearts develop calcium overload secondary to SR calcium leak. Glycative damage of RyR2, favored by deficient dicarbonyl detoxification capacity, contributes to calcium leak and mitochondrial damage in the senescent myocardium.

False Lumen Flow Assessment by Magnetic Resonance Imaging and Long-Term Outcomes in Uncomplicated Aortic Dissection.

BACKGROUND: Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist. OBJECTIVES: The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters. METHODS: One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD. RESULTS: After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter >45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events. CONCLUSIONS: High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter >45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.

An Uncommon Cause of Dyspnea: Usefulness of Multimodality Cardiac Imaging.

Pericardial lipomas are very uncommon benign primary cardiac tumors. We describe the case of a patient with symptomatic large pericardial mass who presented with heart failure. Multimodality cardiac imaging helped us in the diagnosis of this unusual entity. (Level of Difficulty: Intermediate.).

Changes in the diagnosis and management of acute aortic syndrome and associated mortality in the last 20 years.

INTRODUCTION AND OBJECTIVES: Mortality is high in acute aortic syndrome (AAS), which therefore requires early treatment. This study aimed to analyze changes in the diagnosis and treatment of AAS over 20 years at our center. METHODS: From 1999 to 2018, 451 patients diagnosed with AAS (336 men; mean age, 60.9±12.4 years) were prospectively included (270 type A and 181 type B). Clinical variables, diagnosis, treatment, and in-hospital complications were analyzed. RESULTS: The use of computed tomography (CT) as the first-line diagnostic technique increased from 62.8% to 94.2% (P <.001). Surgical treatment of type A AAS rose from 67.4% to 82.5% (P=.09). Mortality from type A AAS decreased significantly from 53.1% to 26.3% (P <.001) as a result of the fall in mortality from surgical treatment (from 45.4% to 17.0%; P <.001). The use of medical treatment alone for type B AAS decreased from 91.8% to 61.7% (P <.001) due to the greater use of endovascular treatment. Mortality from type B AAS showed no significant reduction (16.2% to 10.6%; P=.15). CONCLUSIONS: The diagnosis and treatment of AAS has changed substantially in the last 2 decades. CT has become the first-line diagnostic technique for AAS. In type A AAS, mortality has fallen significantly due to improvements in the results of surgical treatment. In type B AAS, the use of medical treatment alone has decreased due to the expansion of endovascular treatment, although in-hospital mortality has not decreased significantly.