Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study.

Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (p<0.001) and were identified as independent cardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target.

Aortitis as a Rare Cause of Aortic Aneurysm and Valve Regurgitation: Is Repair Precluded?

Aortitis is an infrequent cause of aortic root dilatation and aortic valve regurgitation. Valve-sparing procedures have been proposed, but there is not clear evidence of which is the treatment of choice. We report the case of a 38-year-old pregnant lady with a diagnosis of idiopathic aortitis associated with aortic root aneurysm and severe aortic valve regurgitation.

Quality of life, satisfaction and outcomes after ministernotomy versus full sternotomy isolated aortic valve replacement (QUALITY-AVR): study protocol for a randomised controlled trial.

BACKGROUND: During the last decade, the use of ministernotomy in cardiac surgery has increased. Quality of life and patient satisfaction after ministernotomy have never been compared to conventional full sternotomy in randomised trials. The aim of the study is to determine if this minimally invasive approach improves quality of life, satisfaction and clinical morbimortality outcomes. METHODS/DESIGN: The QUALITY-AVR trial is a single-blind, single-centre, independent, and pragmatic randomised clinical trial comparing ministernotomy ("J" shaped upper hemisternotomy toward right 4th intercostal space) to full sternotomy in patients with isolated severe aortic stenosis scheduled for elective aortic valve replacement. One hundred patients will be randomised in a 1:1 computational fashion. Sample size was determined for the primary end point with alpha error of 0.05 and with power of 90% in detecting differences between intervention groups of ≥ 0.10 points in change from baseline quality of life Questionnaire EuroQOL-index (EQ-5D-5 L®), measured at 1, 6 or 12 months. Secondary endpoints are: the differences in change from other baseline EQ-5D-5 L® utilities (visual analogue scale, Health Index and Severity Index), cardiac surgery specific satisfaction questionnaire (SATISCORE®), a combined safety endpoint of four major adverse complications at 1 month (all-cause mortality, acute myocardial infarction, neurologic events and acute renal failure), bleeding through drains within the first 24 h, intubation time, postoperative hospital and intensive care unit length of stay, transfusion needs during the first 72 h and 1-year survival rates. Clinical follow up is scheduled at baseline, 1, 6, and 12 months after randomization. All clinical outcomes are recorded following the Valve Academic Research Consortium 2 criteria. DISCUSSION: The QUALITY-AVR trial aims to test the hypothesis that ministernotomy improves quality of life, satisfaction and clinical outcomes in patients referred for isolated aortic valve replacement. Statistically significant differences favouring ministernotomy could modify the surgical "gold standard" for aortic stenosis surgery, and subsequently the need to change the control group in transcatheter aortic valve implantation trials. Recruitment started on 18 March 2016. In November 2017, 75 patients were enrolled. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02726087 . Registered on 13 March 2016.

GATA5 and endothelial nitric oxide synthase expression in the ascending aorta is related to aortic size and valve morphology.

BACKGROUND: The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves. METHODS: Samples from 84 patients (33 tricuspid, 32 bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction. RESULTS: GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p < 0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p < 0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter. CONCLUSIONS: Our data suggest that GATA5, possibly through upregulation of eNOS, plays a role in the development of aortic dilatation in patients with unicuspid and bicuspid aortic valves. The differential gene expression in patients with unicuspid compared with bicuspid aortic valves suggests that the pathogenesis of both aortic valve anomalies may be different.

Short- and long-term outcomes of surgery for severe tricuspid regurgitation.

INTRODUCTION AND OBJECTIVES: There is little data available for Spain on the outcomes of surgical treatment for severe tricuspid regurgitation. The aim of this study was to analyze clinical and echocardiographic outcomes in a series of patients who received surgical treatment for severe tricuspid regurgitation and to compare outcomes according to the operative approach to valve repair or replacement. METHODS: Retrospective study in 119 consecutive patients with severe tricuspid regurgitation undergoing valve surgery between April 1996 and February 2010. RESULTS: A total of 61 ringless and 23 ring annuloplasties were performed and 11 bioprostheses and 24 mechanical prostheses were implanted. Perioperative mortality was 18.5% and was associated with age and cardiopulmonary bypass time. During clinical follow-up (median, 41 [interquartile range, 24-89] months), 2 reoperations were required in the ring annuloplasty and mechanical prosthesis groups; prosthetic thrombosis was diagnosed in 4 patients in the latter group. Total mortality after follow-up was 29.9% and was associated with age>70 years and extracorporeal circulation time. The emergence of new severe tricuspid regurgitation was associated with age and ringless annuloplasty (P=.04). CONCLUSIONS: Ringless repair was significantly associated with recurrence of severe tricuspid regurgitation. The use of mechanical prostheses was associated with a high rate of thrombosis. No significant differences in perioperative or total mortality were found between the different methods used for repair or valve replacement.

Neointimal hyperplasia associated with the use of u-clip.

The U-Clip (Coalescent Surgical, Sunnydale, CA USA) allows the surgeon to create an interrupted anastomosis in the same amount of time that is required for a continuous anastomosis with the elimination of knotting. Its use is indicated especially in minimally invasive surgery. We describe a case of a patient in which the proximal anastomosis was performed by interrupted suture with Coalescent U-Clip anastomotic device. Six months later, he presented with stenosis of the anastomosis, and intravascular ultrasound showed anastomotic neointimal hyperplasia.

Long-term predictors of mortality and functional recovery after aortic valve replacement for severe aortic stenosis with left ventricular dysfunction.

INTRODUCTION AND OBJECTIVES: At present, surgery is the only recommended effective treatment for severe aortic stenosis. However, the surgical risk is increased when left ventricular dysfunction is present. The aim of this study was to identify predictors of postoperative and long-term mortality and functional improvement after valve replacement in patients with severe aortic stenosis and left ventricular dysfunction. METHODS: Between 1996 and 2008, 635 consecutive patients with severe aortic stenosis underwent surgery. Early postoperative mortality in the 82 with an ejection fraction <40% was 19.5%. The following independent predictors of early postoperative mortality were identified: female sex (odds ratio [OR]=2.60; 95% confidence interval [CI], 2.20-89.0; P=.004), mild mitral regurgitation (OR=2.38; 95% CI, 1.40-80.0; P=.020) and coronary artery disease (OR=2.09; 95% CI, 1.26-51.0; P=.027). RESULTS: During the mean follow-up period of 42.59+/-40.83 months, overall mortality was 18.8% and cardiovascular mortality was 11.3%. The only factor associated with increased mortality during follow-up was a low postoperative cardiac output (OR=4.40; 95% CI, 1.20-15.5; P=.02). In total, 70.5% showed early improvement in ventricular function, the predictors of which were: no improvement following a previous myocardial infarction (P=.04), no revascularized coronary lesions (P=.04), and a low aortic valve pressure gradient (P=.02). Functional class improved significantly during follow-up in 93.4% of patients. CONCLUSIONS: Despite considerable early postoperative mortality in patients with aortic stenosis and left ventricular dysfunction, over the long term there was evidence of better survival coupled to improved ventricular function and functional class.

Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities.

OBJECTIVES: The aim of this study was to decide whether bicuspid aortic valves (BAVs) with fused right and noncoronary leaflets (R-N) and BAVs with fused right and left leaflets (R-L) have different etiologies or are the product of a single diathesis. BACKGROUND: The BAV is the most common congenital cardiac malformation. The R-N and R-L BAVs are the most frequent BAV subtypes. METHODS: The study was carried out in adult and embryonic hearts of endothelium nitric oxide synthase knock-out mice and inbred Syrian hamsters with a high incidence of R-N and R-L BAVs, respectively. The techniques used were histochemistry, immunohistochemistry, and scanning electron microscopy. RESULTS: The R-N BAVs result from a defective development of the cardiac outflow tract (OT) endocardial cushions that generates a morphologically anomalous right leaflet. The left leaflet develops normally. The R-L BAVs are the outcome of an extrafusion of the septal and parietal OT ridges that thereby engenders a sole anterior leaflet. The noncoronary leaflet forms normally. CONCLUSIONS: The R-N and R-L BAVs are different etiological entities. The R-N BAVs are the product of a morphogenetic defect that happens before the OT septation and that probably relies on an exacerbated nitric oxide-dependent epithelial-to-mesenchymal transformation. The R-L BAVs result from the anomalous septation of the proximal portion of the OT, likely caused by a distorted behavior of neural crest cells. Care should be taken in further work on BAV genetics because R-N and R-L BAVs might rely on different genotypes. Detailed screening for R-N and R-L BAVs should be performed for a better understanding of the relationships between these BAV morphologic phenotypes and other heart disease.

Válvula aórtica bicúspide: resultados a largo plazo de la cirugía reparadora / Long-term Results with Reconstructiva Surgery of the Bicuspid Aortic Valve

Introducción: La válvula aórtica bicúspide es la anomalía congénita cardíaca más frecuente. En pacientes con requerimienro de cirugía, el tratamiento tradicional ha sido la sustitución valvular. La introducción del concepto de reparación de la válvula aórtica bicúspide ha llevado a nuestro grupo a reproducir las técnicas de reparación, las cuales se han estandarizado y aplicado de manera homogénea en nuestras instituciones. Objetivos: Revisar la experiencia conjunta de tres centros, con la presentación de los resultados a mediano y a largo plazos de la reparación valvular. Material y métodos: Entre octubre de 1995 y febrero de 2013 se intervinieron 666 pacientes con válvulas bicúspides e insuficiencia aórtica y/o aneurisma de la aorta. De ellos, 254 presentaban insuficiencia aórtica aislada y 412, aneurisma o disección. Se reconstruyó la válvula en todos los pacientes (en 254 como procedimiento aislado, en 281 "remodelación de la raíz", en 129 remodelación de la unión sinotubular y en 2 "reimplantación"). Resultados: La mortalidad fue de 3/666 (0,5%): 1/254 (0,4%) tras reparación valvular aislada y 2/410 (0,5%) tras reparación más reemplazo de la aorta. En pacientes con cirugía asociada (coronaria, reparación mitral/tricúspide) fue de 1/77 (1,3%). Durante el seguimiento murieron 12 pacientes (supervivencia a los 10 años: 95%). Las libertades de reoperación y de sustitución valvular a los 10 y 15 años fueron del 80% y 77% y del 86% y 83%, respectivamente. La libertad de reoperación a los 10 años fue superior en el reemplazo de la raíz (86%) o la aorta tubular (84%) en comparación con la reparación aislada (74%; p = 0,005). La libertad de cualquier complicación relacionada con la válvula fue del 80% y 77% a los 10 y 15 años, respectivamente, y fue mejor para reparación incluyendo "remodelación de la raíz" (87% y 82%) que para reparación aislada (77% y 77%; p = 0,04). Conclusiones: La reparación de la válvula aórtica bicúspide es un procedimiento seguro y duradero, con una incidencia baja de "complicaciones relacionadas con la válvula" a mediano y a largo plazos.

Introduction: Bicuspid aortic valve is the most common congenital heart disease. Traditionally, aortic valve replacement has been the approach for patients requiring surgery. After introduction of the bicuspid aortic valve repair concept, our group began reproducing these techniques, which have been standardized and homogeneously applied at our institutions. Objectives: The aim of this study was to review the conjoint experience of three centers and show the mid- and long-term results of bicuspid aortic valve repair. Methods: Between October 1995 and February 2013, 666 patients with bicuspid aortic valve underwent surgery for aortic regurgitation and/or aortic aneurysm. Isolated aortic regurgitation was present in 254 patients, and 412 had aortic aneurysm or dissection. The valve was reconstructed in all the patients (isolated valve repair in 254, "remodelling of the aortic root" in 281, remodelling of the sinotubular junction in 129 and "reimplantation" technique in 2). Results: Mortality was 3/666 (0.5%): 1/254 (0.4%) after isolated valve repair and 2/410 (0.5%) after valve repair plus aortic replacement. In patients with combined procedures (coronary revascularization or mitral/tricuspid valve repair), mortality was 1/77 (1.3%). During follow-up, 12 patients died (10-year survival: 95%). Freedom from reoperation and from aortic valve replacement at 10 and 15 years were 80% and 77%, and 86% and 83%, respectively Freedom from reoperation at 10 years was higher with aortic root (86%) or tubular aorta (84%) replacement, compared with isolated valve repair (74%; p = 0.005). Freedom from any valve-related complication was 80% and 77% at 10 and 15 years, respectively, and was better for valve repair including "remodelling of the aortic root" (87% and 82%) than for isolated repair (77% and 77%; p = 0.04). Conclusions: Bicuspid aortic valve repair is a safe, long-lasting procedure, with a low incidence of mid- and long-term "valve-related complications".

[Influence of sex on perioperative outcomes in patients undergoing valve replacement for severe aortic stenosis]. / Influencia del sexo en el pronóstico perioperatorio de pacientes sometidos a sustitución valvular por estenosis aórtica severa.

INTRODUCTION AND OBJECTIVES: The influence of sex on the prognosis of patients undergoing aortic valve replacement for severe stenosis is unclear. Nevertheless, a number of studies have regarded sex as an independent risk factor. The aim of this study was to evaluate the influence of sex on perioperative outcomes in patients undergoing valve replacement for severe aortic stenosis. METHODS: This retrospective study involved 577 consecutive patients who underwent aortic valve replacement surgery for severe aortic stenosis between 1996 and April 2007. RESULTS: Women (44% of patients) were older than men (70.3+/-7.9 years vs. 66.8+/-9.8 years; P< .001), had a smaller body surface area (1.68+/-0.15 m(2) vs. 1.83+/-0.16 m(2); P< .001), more often had arterial hypertension (73% vs. 49%; P< .001), diabetes mellitus (33.5% vs. 24.5%; P=.001) and ventricular hypertrophy (89.1% vs. 83.1%; P< .001), and less often had coronary artery disease (19.1% vs. 31.8%; P< .001) and severe ventricular dysfunction (7.9% vs. 17.4%; P< .001). Nevertheless, women more often suffered acute myocardial infarction perioperatively (3.9% vs. 0.9%; P=.016), had a low cardiac output in the postoperative period (30.3% vs. 22.3%; P=.016) and experienced greater perioperative mortality (13% vs. 7.4%; P=.019) than men. However, after adjustment for various confounding factors, female sex was not a significant independent risk factor for mortality (odds ratio = 2.40; 95% confidence interval, 0.79-7.26; P=.119). CONCLUSIONS: Perioperative mortality in women with severe aortic stenosis who underwent valve replacement was high. However, after adjustment for potential confounding factors, particularly body surface area, female sex was not an independent risk factor for mortality.

Severe stenosis of anastomoses by using the symmetry aortic connector system.

The St. Jude Medical Symmetry Aortic Connector System was developed to create the proximal vein graft anastomoses in coronary artery bypass grafting. We describe three symptomatic patients with severe stenosis of the proximal anastomosis several months after using the Symmetry aortic connector system. Intravascular ultrasound study showed anastomotic neointimal hyperplasia.

Cirugía de la regurgitación tricuspídea grave: resultados a corto y largo plazo / Short- and long-term outcomes of surgery for severe tricuspid regurgitation

Introducción y objetivos. En nuestro medio hay pocos datos sobre los resultados del tratamiento quirúrgico de la insuficiencia tricuspídea grave. Nuestro objetivo es analizar los resultados clínicos y ecocardiográficos de nuestra población con insuficiencia tricuspídea grave sometida a cirugía comparándolos según el tipo de reparación o de sustitución valvular. Métodos. Realizamos un estudio retrospectivo incluyendo a 119 pacientes consecutivos con insuficiencia tricuspídea grave sometidos a cirugía de dicha válvula entre abril de 1996 y febrero de 2010. Resultados. Se realizaron 61 anuloplastias sin anillo y 23 con anillo, y se implantaron 11 prótesis biológicas y 24 mecánicas. La mortalidad perioperatoria fue del 18,5%, y se asociaron a ella la edad y el tiempo de circulación extracorpórea. Durante el seguimiento clínico (mediana, 41 [intervalo intercuartílico, 24-89] meses), el grupo anuloplastia con anillo precisó dos reoperaciones, al igual que el grupo de prótesis mecánica, en el que se diagnosticó trombosis protésica a 4 pacientes. La mortalidad total tras seguimiento fue del 29,9%, y se asociaron a ella la edad > 70 años y el tiempo de circulación extracorpórea. La aparición de nueva insuficiencia tricuspídea grave se asoció a la edad y la anuloplastia sin anillo (p = 0,04). Conclusiones. La reparación sin anillo se asoció significativamente con recurrencia de insuficiencia tricuspídea grave. El implante de prótesis mecánica se asoció a una elevada tasa de trombosis en el seguimiento. No se encontraron diferencias significativas en la mortalidad perioperatoria o total según el tipo de reparación o sustitución valvular (AU)

Introduction and objectives: There is little data available for Spain on the outcomes of surgical treatment for severe tricuspid regurgitation. The aim of this study was to analyze clinical and echocardiographic outcomes in a series of patients who received surgical treatment for severe tricuspid regurgitation and to compare outcomes according to the operative approach to valve repair or replacement. Methods: Retrospective study in 119 consecutive patients with severe tricuspid regurgitation undergoing valve surgery between April 1996 and February 2010. Results: A total of 61 ringless and 23 ring annuloplasties were performed and 11 bioprostheses and 24 mechanical prostheses were implanted. Perioperative mortality was 18.5% and was associated with age and cardiopulmonary bypass time. During clinical follow-up (median, 41 [interquartile range, 24-89] months), 2 reoperations were required in the ring annuloplasty and mechanical prosthesis groups; prosthetic thrombosis was diagnosed in 4 patients in the latter group. Total mortality after follow-up was 29.9% and was associated with age>70 years and extracorporeal circulation time. The emergence of new severe tricuspid regurgitation was associated with age and ringless annuloplasty (P=.04). Conclusions: Ringless repair was significantly associated with recurrence of severe tricuspid regurgitation. The use of mechanical prostheses was associated with a high rate of thrombosis. No significant differences in perioperative or total mortality were found between the different methods used for repair or valve replacement (AU)

Predictores de mortalidad y recuperación funcional a largo plazo en el reemplazo valvular por estenosis aórtica severa con disfunción ventricular / Long-term predictors of mortality and functional recovery after aortic valve replacement for severe aortic stenosis with left ventricular dysfunction

Introducción y objetivos. El tratamiento quirúrgico de la estenosis aórtica severa es el único efectivo recomendado actualmente para esta patología, pero el riesgo quirúrgico aumenta con la disfunción ventricular izquierda. Nuestro objetivo fue identificar predictores de mortalidad y mejoría funcional en el postoperatorio y a largo plazo tras reemplazo valvular en pacientes con estenosis aórtica y disfunción ventricular severa. Métodos. Entre 1996 y 2008, 635 pacientes con estenosis aórtica severa fueron intervenidos, 82 con fracción de eyección < 40%, con mortalidad postoperatoria precoz del 19,5%. Identificamos como predictores independientes de mortalidad postoperatoria precoz el sexo femenino (OR = 2,60; IC del 95%, 2,20-89; p = 0,004), la regurgitación mitral no severa (OR = 2,38; IC del 95%,1,40-80; p = 0,020) y las lesiones coronarias (OR = 2,09;IC del 95%, 1,26-51; p = 0,027).Resultados. Tras seguimiento medio de 42,59 ± 40,83meses, la mortalidad global fue del 18,8% y la cardiovascular, del 11,3%. Sólo el bajo gasto cardiaco postoperatorio(OR = 4,40; IC del 95%, 1,20-15,50; p = 0,02)se relacionó con mayor mortalidad en el seguimiento. El70,5% presentó mejoría precoz de la función ventricular, siendo predictores de ausencia de mejoría el infarto previo(p = 0,04), las lesiones coronarias no revascularizadas (p = 0,04) y un gradiente aórtico reducido (p = 0,02). El93,4% mejoró su grado funcional significativamente durante el seguimiento. Conclusiones. Pese a la considerable mortalidad postoperatoria precoz de los pacientes con estenosis aórtica y disfunción ventricular izquierda, a largo plazo se observa una supervivencia elevada junto a mejora de la función ventricular y del grado funcional (AU)

Introduction and objectives. At present, surgery is the only recommended effective treatment for severe aortic stenosis. However, the surgical risk is increased when left ventricular dysfunction is present. The aim of this study was to identify predictors of postoperative and long-term mortality and functional improvement after valve replacement in patients with severe aortic stenosis and left ventricular dysfunction. Methods. Between 1996 and 2008, 635 consecutive patients with severe aortic stenosis underwent surgery. Early postoperative mortality in the 82 with an ejection fraction <40% was 19.5%. The following independent predictors of early postoperative mortality were identified: female sex (odds ratio [OR]=2.60; 95% confidence interval[CI], 2.20-89.0; P=.004), mild mitral regurgitation (OR=2.38;95% CI, 1.40-80.0; P=.020) and coronary artery disease(OR=2.09; 95% CI, 1.26-51.0; P=.027).Results. During the mean follow-up period of42.59±40.83 months, overall mortality was 18.8% and cardiovascular mortality was 11.3%. The only factor associated with increased mortality during follow-up was allow postoperative cardiac output (OR=4.40; 95% CI, 1.20-15.5; P=.02). In total, 70.5% showed early improvement in ventricular function, the predictors of which were: no improvement following a previous myocardial infarction(P=.04), no revascularized coronary lesions (P=.04), and a low aortic valve pressure gradient (P=.02). Functional class improved significantly during follow-up in 93.4% of patients. Conclusions. Despite considerable early postoperative mortality in patients with aortic stenosis and left ventricular dysfunction, over the long term there was evidence of better survival coupled to improved ventricular function and functional class (AU)