Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in the
(fibrillin-1) gene encoding a large glycoprotein in the extracellular matrix called ...fibrillin-1. The major complication of this connective disorder is the risk to develop thoracic aortic aneurysm. To date, no effective pharmacologic therapies have been identified for the management of thoracic aortic disease and the only options capable of preventing aneurysm rupture are endovascular repair or open surgery. Here, we have studied the role of mitochondrial dysfunction in the progression of thoracic aortic aneurysm and mitochondrial boosting strategies as a potential treatment to managing aortic aneurysms.
Combining transcriptomics and metabolic analysis of aortas from an MFS mouse model (
) and MFS patients, we have identified mitochondrial dysfunction alongside with mtDNA depletion as a new hallmark of aortic aneurysm disease in MFS. To demonstrate the importance of mitochondrial decline in the development of aneurysms, we generated a conditional mouse model with mitochondrial dysfunction specifically in vascular smooth muscle cells (VSMC) by conditional depleting Tfam (mitochondrial transcription factor A;
mice). We used a mouse model of MFS to test for drugs that can revert aortic disease by enhancing Tfam levels and mitochondrial respiration.
The main canonical pathways highlighted in the transcriptomic analysis in aortas from
mice were those related to metabolic function, such as mitochondrial dysfunction. Mitochondrial complexes, whose transcription depends on Tfam and mitochondrial DNA content, were reduced in aortas from young
mice. In vitro experiments in
-silenced VSMCs presented increased lactate production and decreased oxygen consumption. Similar results were found in MFS patients. VSMCs seeded in matrices produced by Fbn1-deficient VSMCs undergo mitochondrial dysfunction. Conditional Tfam-deficient VSMC mice lose their contractile capacity, showed aortic aneurysms, and died prematurely. Restoring mitochondrial metabolism with the NAD precursor nicotinamide riboside rapidly reverses aortic aneurysm in
mice.
Mitochondrial function of VSMCs is controlled by the extracellular matrix and drives the development of aortic aneurysm in Marfan syndrome. Targeting vascular metabolism is a new available therapeutic strategy for managing aortic aneurysms associated with genetic disorders.
Left atrial appendage occlusion has become an alternative for long-term anticoagulation for patients with non-valvular atrial fibrillation. Although the procedure is safe, life-threatening ...complications such as embolization of the device or cardiac tamponade might occur. We present a case of a LAmbre device that migrated 4 days after being implanted and remained trapped in the mitral valve. Secondary massive mitral regurgitation with severe stenosis and haemodynamic instability required emergency surgery. The device was successfully removed, but severe damage in the anterior leaflet and chords forced a valve replacement.
Abstract
Cardiac paragangliomas are extremely rare. Sometimes surgical resection is a challenge owing to the proximity of vital structures and coronary arteries involvement. We report a case of a ...34-year-old man with cardiac paragangliomas located between right atrium and right ventricle with a feeding blood supply from collaterals of the right coronary artery. In this case, we implanted a covered single stent (PK Papyrus®) in the right coronary artery with the objective of embolizing collateral branches and to reinforce the coronary artery wall. Although tumour mass was not reduced, vascularization was minimized, and this hybrid strategy made the surgery easier and safer.
A 46-year-old woman presented for a routine echocardiogram, which revealed a giant atrial septal aneurysm (ASA) with an atrial septal defect (ASD). We surgically excised the ASA and closed the ASD ...with a pericardial patch. ASA, although rare, poses embolic risks, thus necessitating closure when associated with shunts. Optimal stroke prevention remains uncertain.
Background
The use of cardioplegia solutions as a myocardial protection technique is essential during cardiac surgery with cardiopulmonary bypass. The del Nido cardioplegia solution (DNS) has been ...widely used as a myocardial preservation technique for pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Its unique pharmacological features have created growing interest for adult cardiac surgery, especially for elderly patients or those with ventricular dysfunction who are more prone to ischemia-reperfusion injury. Ever since its implementation, several retrospective studies have been published to validate the efficacy, safety, and efficiency of DNS in adult patients undergoing coronary revascularization, valve replacement, or combined procedures. Recently, a meta-analysis based on nine retrospective studies was published claiming the noninferiority of DNS compared to other conventional cardioplegia solutions. Few prospective randomized studies have been conducted whose primary outcome was the assessment of DNS clinical efficacy compared to other solutions commonly used in adult patients.
Objective
The aim of this randomized clinical trial is to assess the benefits of DNS compared to Cardi-Braun blood cardioplegia solution in clinical and biochemical terms regarding myocardial protection during adult cardiac surgery.
Methods
This is the protocol of a controlled, randomized, single-center clinical trial carried out at the Puerta de Hierro Majadahonda University Hospital in Spain. A total of 474 participants over the age of 18 years undergoing elective cardiac surgery with cardiopulmonary bypass will be assigned to groups by simple randomization to receive either DNS or Cardi-Braun blood cardioplegia solution. The primary outcome will be the differences between groups in myocardial protection in biochemical terms (ie, perioperative troponin levels) and clinical terms (ie, presence of the composite variable acute cardiovascular event). The clinical trial will be carried out under conditions of respect for the fundamental rights of the person and the ethical principles that affect biomedical research with human beings, as well as in accordance with international recommendations contained in the Declaration of Helsinki and its subsequent revisions.
Results
The inclusion process started in 2018. Data cleaning and analyses are expected to take place in the fall of 2020 and the results are expected in January 2021.
Conclusions
This study is particularly relevant as it will be one of the first to analyze the clinical effects of del Nido cardioplegia on the basis of direct myocardial protection parameters. In light of published studies, carrying out prospective studies based on primary clinical objectives with a larger sample, high-risk patients, and longer cardiopulmonary bypass times continues to be necessary. We believe that our study addresses an important gap in the knowledge of del Nido cardioplegia in adult patient cardiac surgery and will be able to clarify the possible benefits of this method in a large population of patients undergoing these procedures.
Trial Registration
European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2017-005144-14; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-005144-14+; ClinicalTrials.gov NCT04094168; https://clinicaltrials.gov/ct2/show/NCT04094168
International Registered Report Identifier (IRRID)
DERR1-10.2196/17826
Abstract
OBJECTIVES
The goal of this study was to analyse early- and long-term outcomes of aortic valve reimplantation (David operation) in patients with heritable thoracic aortic disease.
METHODS
...This is a retrospective observational analysis using data from a prospectively maintained surgical database from March 2004 to April 2021. Patients with heritable thoracic aortic disease were included in the study.
RESULTS
A total of 157 patients with aortic root aneurysm with the diagnosis of heritable thoracic aortic disease received the David procedure. Marfan syndrome was found in 143 (91.1%) patients, Loeys-Dietz in 13 and Ehler-Danlos in 1 patient. The median age was 35.0 (IQR: 17.5) years and the median ascending aorta diameter in the Valsalva sinuses was 48 mm (IQR: 4). A Valsalva graft was used in 8 patients; the David V technique was performed in the rest of the cases. The median follow-up time was 7.3 years standard deviation: 0.58, 95% confidence interval (CI): 6.12–8.05. Only 2 patients died during the follow-up period. The overall survival was 99% (95% CI: 95%; 99%); 98% (95% CI: 92%; 99%); and 98% (95% CI: 92%; 99%) at 5, 10 and 15 years. Freedom from significant aortic regurgitation (AR> II), reintervention and postoperative type-B dissection was 90% (95% CI: 77%; 95%), 96% (95% CI: 91%; 99%) and 87% (95% CI: 68%; 95%) at 15 years, respectively. No differences were found in any outcome between Marfan syndrome and Loeys-Dietz syndrome. No statistically significant differences in survival were found when we compared expected gender- and age-specific population survival values.
CONCLUSIONS
The David operation is an excellent option for the treatment of patients with heritable thoracic aortic disease and dilatated aortic root. Surgical expertise in referral centres is essential to achieve the best long-term results.
Connective tissue syndromes are genetic disorders that frequently involve musculoskeletal, cardiovascular and ocular manifestations.
El tratamiento quirúrgico preventivo de los aneurismas de raíz de aorta fue posible gracias a la técnica descrita en la década de los sesenta por Bentall-Bono, que permitió una mejora de la ...supervivencia en este tipo de pacientes. La cirugía de preservación valvular aórtica surge para evitar los efectos adversos derivados de la anticoagulación crónica y de las prótesis valvulares relacionadas con este procedimiento. Los resultados de estas técnicas en centros de referencia son excelentes, estableciéndose como una herramienta fundamental en el arsenal terapéutico del cirujano cardiovascular en esta patología. Para obtener los mejores resultados, su uso debe quedar limitado a centros de experiencia en este tipo de patologías.
The development of the Bentall-Bono technique in the 1960s allowed the prophylactic treatment of the aortic root aneurysms, increasing the survival of these patients. Valve sparing techniques were developed later, in a response to the potential complications related to mechanical prosthesis and long-term anticoagulation associated to the Bentall-Bono procedure. The results of these techniques in the hands of experienced teams are excellent, and they have become an important tool in the therapeutic arsenal of the cardiovascular surgeon in this pathology. In order to achieve the best surgical results, these techniques should be performed in experienced centres.
Controlled donation after circulatory death (cDCD) has emerged as one of the main strategies for increasing the organ donor pool. Because of the ischemic injury that follows the withdrawal of ...life-sustaining therapies, hearts from cDCD donors have not been considered for transplantation until recently. The ex-situ perfusion of hearts directly procured from cDCD donors has been used to allow the continuous perfusion of the organ and the assessment of myocardial viability prior to transplantation. Based on our experience with abdominal normothermic regional perfusion in cDCD, we designed a protocol to recover and validate hearts from cDCD donors using thoraco-abdominal normothermic regional perfusion without the utilization of an ex-situ device.
We describe the first case of a cDCD heart transplant performed with this approach in Spain. The donor was a 43-year-old asthmatic female diagnosed with severe hypoxic encephalopathy. She was considered a potential cDCD donor and a suitable candidate for multiorgan procurement including the heart via thoraco-abdominal normothermic regional perfusion. The heart recipient was a 60-year-old male diagnosed with amyloid cardiomyopathy. Cold ischemia time was 55 min. The surgery was uneventful.
This case report, the first of its kind in Spain, supports the feasibility of evaluating and successfully transplanting cDCD hearts without the need for ex-situ perfusion based on the use of thoraco-abdominal normothermic regional perfusion opening the way for multiorgan donation in cDCD.
To the Editor, Chronic heart failure (CHF) is the third leading cause of cardiovascular death in developed countries, and is mostly of ischemic etiology.1 Despite the optimal medical therapy based on ...the clinical practice guidelines, many patients remain symptomatic for whom different procedures have become available over the last few years to stop pathological ventricular remodeling. The Revivent system (BioVentrix Inc., United States) is a hybrid ventricular reconstruction procedure that works by implanting micro-anchors via endovascular access and left mini thoracotomy to create a longitudinal plication of scar tissue without the need for mid sternotomy or extracorporeal circulation. Basically it is indicated in patients with ischemic heart disease and anterolateral or apical aneurysmal regions with transmural scar in both the left ventricle (LV) and right septum (RS)-according to the magnetic resonance imaging-to prevent muscle tears, and who still have persistent advanced CHF and NYHA functional class (FC) > III despite the optimal medical therapy.2 Biffi et al. confirmed an in-hospital mortality rate of 1.4%, and a 1-year survival rate of 90% in 203 patients.3 The STICH4 and RESTORE5 clinical trials revealed in-hospital mortality rates of 6% and 5.1%, respectively, and 18-month survival rates of 85% and 88%, respectively, after surgical therapy in patients...
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