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Aim To obtain a quantitative expression profile of the main genes involved in the cAMP-signaling cascade in human control atria and in different cardiac pathologies. Methods and results Expression of 48 target genes playing a relevant role in the cAMP-signaling cascade was assessed by RT-qPCR. 113 samples were obtained from right atrial appendages (RAA) of patients in sinus rhythm (SR) with or without atrium dilation, paroxysmal atrial fibrillation (AF), persistent AF or heart failure (HF); and left atrial appendages (LAA) from patients in SR or with AF. Our results show that right and left atrial appendages in donor hearts or from SR patients have similar expression values except for AC7 and PDE2A. Despite the enormous chamber-dependent variability in the gene-expression changes between pathologies, several distinguishable patterns could be identified. PDE8A, PI3Kγ and EPAC2 were upregulated in AF. Different phosphodiesterase (PDE) families showed specific pathology-dependent changes. Conclusion By comparing mRNA-expression patterns of the cAMP-signaling cascade related genes in right and left atrial appendages of human hearts and across different pathologies, we show that 1) gene expression is not significantly affected by cardioplegic solution content, 2) it is appropriate to use SR atrial samples as controls, and 3) many genes in the cAMP-signaling cascade are affected in AF and HF but only few of them appear to be chamber (right or left) specific. Topic Genetic changes in human diseased atria. Translational perspective The cyclic AMP signaling pathway is important for atrial function. However, expression patterns of the genes involved in the atria of healthy and diseased hearts are still unclear. We give here a general overview of how different pathologies affect the expression of key genes in the cAMP signaling pathway in human right and left atria appendages. Our study may help identifying new genes of interest as potential therapeutic targets or clinical biomarkers for these pathologies and could serve as a guide in future gene therapy studies.

Resumen Introduccion y objetivos En endocarditis infecciosa (EI), la decision quirurgica es dificil. Un alto porcentaje de pacientes con indicacion quirurgica no son intervenidos. El objetivo fue evaluar el pronostico a corto y largo plazo de los pacientes con indicacion quirurgica, comparando los que se sometieron a cirugia con los que no lo hicieron. Metodos Se incluyeron 271 pacientes con EI izquierda e indicacion quirurgica tratados en el centro desde 2003 a 2018. Ochenta y tres pacientes (31%) no fueron finalmente operados. El objetivo primario fue la mortalidad a 60 dias y el secundario desde el dia 61 a los 3 anos de seguimiento. Se realizo regresion de Cox multivariable y emparejamiento por puntuacion de propension. Resultados A los 60 dias, 40 (21,3%) pacientes operados y 53 (63,9%) pacientes no intervenidos fallecieron (p Conclusiones Dos tercios de los pacientes con indicacion quirurgica no intervenidos fallecieron antes de 60 dias. Entre los supervivientes, la mortalidad a largo plazo depende mas de factores relacionados con comorbilidad previa que del tratamiento recibido durante el ingreso.

INTRODUCTION AND OBJECTIVES In infective endocarditis (IE), decisions on surgical interventions are challenging and a high percentage of patients with surgical indication do not undergo these procedures. This study aimed to evaluate the short- and long-term prognosis of patients with surgical indication, comparing those who underwent surgery with those who did not. METHODS We included 271 patients with left-sided IE treated at our institution from 2003 to 2018 and with an indication for surgery. There were 83 (31%) surgery-indicated not undergoing surgery patients with left-sided infective endocarditis (SINUS-LSIE). The primary outcome was all-cause death by day 60 and the secondary outcome was all-cause death from day 61 to 3 years of follow-up. Multivariable Cox regression and propensity score matching were used for the analysis. RESULTS At the 60-day follow-up, 40 (21.3%) surgically-treated patients and 53 (63.9%) SINUS-LSIE patients died (P

Atrial fibrillation (AF) is a common arrhythmia in the general population and following cardiac surgery. The influence of mitochondrial genomics on AF pathogenesis is not fully understood. We analyzed mitochondrial variables from 78 human atrial samples collected from cardiac surgeries in the following groups: 1) permanent preoperative AF; 2) preoperative sinus rhythm (SR) with postoperative AF; and 3) pre-/postoperative SR. Haplogroup H appeared offer protection against, and haplogroup U predispose to permanent AF. mtDNA content was higher in group 2 than in 3. These findings contribute to a better understanding of the influence of mitochondria on AF pathogenesis., The study was supported by the Ministry of Economy and Competitiveness, Spain for the sample preparation at the Cardiovascular Research Centre and CIBERCV, Spain (SAF2014-58286-C2-1-R).

Background Frailty is a geriatric syndrome that diminishes potential functional recovery after any surgical procedure. Preoperative surgical risk assessment is crucial to calibrate the risk and benefit of cardiac surgery. The aim of this study was to test usefulness of FRAIL Scale and other surgical-risk-scales and individual features of frailty in cardiac aortic valve surgery. Methods Prospective study. From May-2014 to February-2016, we collected 200 patients who underwent aortic valve replacement, either surgically or transcatheter. At 1-year follow-up, quality of life measurements were recorded using the EQ-5D (EuroQol). Univariate and multivariate analyses correlated preoperative condition, features of frailty and predicted risk scores with mortality, morbidity and quality of life at 1 year of follow-up. Results Mean age 78.2y, 56%male. Mean-preoperative-scores: FRAIL scale 1.5(SD 1.02), STS 2.9(SD 1.13), BI 93.8(SD 7.3), ESlog I 12.8(SD 8.5) and GS 7.3 s (SD 1.9). Morbidity at discharge, 6 m and 1 year was 51, 14 and 28%. Mortality 4%. Survival at 6 m/ 1-y was 97% / 88%. Complication-rate was higher in TAVI group due to-vascular complications. Renal dysfunction, anemia, social dependence and GS slower than 7 s were associated with morbidity. On multivariate analysis adjusted STS, BI and GS speed were statistically significant. Quality of life at 1-year follow-up adjusted for age and prosthesis type showed a significant association with STS and FRAIL scale scores. Conclusions Frailty increases surgical risk and is associated with higher morbidity. Preoperative GS slower 7 s, and STS and FRAIL scale scores seem to be reliable predictors of quality of life at 1-year follow-up.

Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis. Mathematical analysis demonstrates that increased stem cell proliferation expedites somatic evolution and expansion of clones with driver mutations. The experimentally determined division rate elevation in atherosclerosis patients is sufficient to produce a 3.5-fold increased risk of clonal hematopoiesis by age 70. We confirm the accuracy of our theoretical framework in mouse models of atherosclerosis and sleep fragmentation by showing that expansion of competitively transplanted Tet2(-/-) cells is accelerated under conditions of chronically elevated hematopoietic activity. Hence, increased hematopoietic stem cell proliferation is an important factor contributing to the association between cardiovascular disease and clonal hematopoiesis.

For almost half a century, cardiac transplant has been the only long-term treatment for patients with end-stage heart failure. Implantable left ventricular assist devices (LVADs) have emerged as a new treatment option for advanced heart failure as destination therapy for patients either too old or not suitable for transplant. A meta-analysis presenting head-to-head comparisons of cardiac transplant versus LVAD as destination therapy (LVAD-DT) found no difference in 1-year mortality rates between LVAD-DT and cardiac transplant (OR 1.49; 95% CI [0.48–4.66]; I2=82.8%). Moreover, a recent subanalysis from the Interagency Registry for Mechanically Assisted Circulatory Support found similar outcomes after LVAD-DT implantation in both transplant and non-transplant centres. The time is right for LVAD-DT in non-transplant centres, provided multidisciplinary heart failure teams and expertise are in place.

Resumen: Introducción y objetivos: Los pacientes adultos con cardiopatías congénitas representan un porcentaje pequeño del total de pacientes trasplantados de corazón. Tradicionalmente se ha asociado a este subgrupo de pacientes a una mayor mortalidad precoz. En nuestro centro hemos experimentado un incremento en el número de pacientes adultos con cardiopatía congénita remitidos para valoración de trasplante. Presentamos nuestra experiencia. Métodos: Entre mayo de 1984 y diciembre del 2014 se realizaron 508 trasplantes cardiacos. De ellos 16 (3%) fueron en adultos con cardiopatía congénita. Se han analizado las características de este grupo, comparando su evolución con el resto de trasplantes de causa no congénita. Resultados: En el grupo de pacientes trasplantados con cardiopatía congénita la causa más frecuente fue la transposición completa de grandes vasos. Los pacientes congénitos trasplantados tuvieron una edad media inferior, menos factores de riesgo cardiovascular y mayor número de intervenciones previas que el grupo de trasplantados no congénitos, todas ellas diferencias estadísticamente significativas (p

Resumen Introduccion y objetivos El grupo de Trabajo de en Reparacion Valvular de la Sociedad Espanola de Cirugia Toracica y Cardiovascular presenta el quinto registro anual de actividad en cirugia reparadora de la valvulas mitral, aortica y tricuspide realizada en Espana en el ano 2015. Material y metodos La recogida de datos se realizo a traves de cuestionario on-line, de forma retrospectiva, voluntaria, anonima y no auditada. Se detallan parametros en cuanto al tipo de cirugia, etiologia, mortalidad y riesgo quirurgico, tanto en el grupo global con en pacientes electivos. Resultados Se obtuvieron datos de 31 centros, con 9.112 intervenciones reportadas. La cirugia mitral reparadora supone el 29,6% de las valvulas mitrales intervenidas, con una amplia diferencia relativa a la etiologia del proceso, asi como muy diferente perfil de riesgo. La tasa de cirugia reparadora aortica continua en ascenso respecto a la sustitucion valvular, aunque con gran variacion intergrupos. La cirugia valvular tricuspide es mayoritariamente reparadora con uso de anillos con un numero estable en el tiempo de reemplazos valvulares. Conclusiones La actividad reparadora mitral esta establecida en la mayoria de los grupos, siendo muy dependiente de etiologia. Se observa un incremento en la tasa de reparacion valvular aortica y permanece estabilizada la actividad sobre la valvula tricuspide.

Background and Aim Tricuspid valve replacement has been associated with high mortality and poor long-term outcomes. We report the preoperative risk factors associated with short and long-term outcomes following tricuspid valve replacement with mechanical prostheses. Methods In 62 patients who underwent mechanical tricuspid valve replacement, clinical, laboratory, and echocardiographic findings were analyzed using both univariate and multivariate analyses to describe operative and long-term mortality. Results In our population (mean age 59 ± 9.7 years, 82.3% female), most common causes of tricuspid valve disease were rheumatic fever (69.4%) and functional regurgitation (19.4%). Operative and long-term mortality were 17.7 and 33.9%, respectively. Age, diabetes mellitus, and coronary artery disease were independently associated with increased long-term mortality. New York Heart Association (NYHA) class and right heart failure symptoms significantly improved during follow-up. Conclusions In this series of mechanical tricuspid valve replacements in patients with predominately rheumatic heart disease, operative and long-term mortality were increased; however, survivors had significant improvement in their NYHA class and freedom from right heart failure symptoms. Three preoperative factors (age, diabetes mellitus, and coronary artery disease) were independently associated with long-term mortality.

Background and objective Pulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Material and methods Since February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance ≥ 1090 dyn/s/cm −5 , and group 2, which included the remaining 120 patients. Results Hospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 ( p = 0.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). Conclusions Pulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery.

Resumen Fundamento y objetivo La cirugia de tromboendarterectomia pulmonar es el tratamiento de eleccion para la hipertension pulmonar tromboembolica cronica; un factor de riesgo para la mortalidad hospitalaria son las resistencias vasculares pulmonares muy elevadas. El objetivo de este trabajo fue analizar los resultados inmediatos y a largo plazo de la cirugia para la hipertension pulmonar tromboembolica cronica en pacientes con hipertension pulmonar muy grave. Material y metodos Desde febrero de 1996 hemos realizado 160 tromboendarterectomias pulmonares. Dividimos esta poblacion en grupo 1 –40 pacientes con resistencias vasculares pulmonares ≥ 1.090 dinas/s/cm −5 – y grupo 2 –los 120 restantes–. Resultados La mortalidad hospitalaria (15 frente a 2,5%), el edema pulmonar de reperfusion (33 frente a 14%) y la insuficiencia cardiaca (23 frente a 3,3%) fueron significativamente mayores en el grupo 1; pero al ano, no hay diferencia en la situacion clinica, hemodinamica y ecocardiografica con el grupo 2. La supervivencia a los 5 anos fue del 77% en el grupo 1 y del 92% en el grupo 2 (p = 0,033). Excluyendo los primeros 46 enfermos, considerados curva de aprendizaje, no hubo diferencia en la mortalidad hospitalaria (3,8 frente a 2,3%) ni en la supervivencia (96,2% en el grupo 1 y 96,2% en el grupo 2 a los 5 anos). Conclusiones La tromboendarterectomia pulmonar tiene una morbimortalidad inicial mayor en pacientes con hipertension pulmonar tromboembolica cronica muy grave, pero obtiene el mismo beneficio a medio-largo plazo. En nuestra experiencia, tras la curva de aprendizaje, la cirugia ofrece la misma seguridad y excelentes resultados a los pacientes mas graves, y ninguna cifra de resistencias vasculares pulmonares deberia ser considerada una contraindicacion absoluta.

Introducción y objetivos: La insuficiencia tricuspídea funcional significativa conlleva una mayor morbimortalidad si no se corrige durante la cirugía valvular izquierda o si reaparece en el seguimiento. La anuloplastia tricuspídea mediante técnicas de sutura presenta una alta tasa de recurrencia de insuficiencia tricuspídea. Actualmente se prefieren las técnicas con anillo protésico, ya que presentan resultados más duraderos en el seguimiento. Los objetivos de este estudio son evaluar los resultados ecocardiográficos a medio plazo de la anuloplastia tricuspídea con anillo rígido tridimensional, así como analizar los factores predictores de recurrencia de insuficiencia tricuspídea significativa. Métodos: Se recogieron los datos clínicos y ecocardiográficos de 260 pacientes intervenidos de anuloplastia tricuspídea mediante anillo rígido tridimensional en nuestro centro. Se llevó a cabo el análisis multivariante mediante regresión logística para determinar los factores de riesgo de reaparición de insuficiencia tricuspídea moderada-grave. Resultados: Tras una mediana de seguimiento de 16 meses (3,9-34,5), 220 pacientes (84,62%) presentaban un ecocardiograma de control. La persistencia/recurrencia de insuficiencia tricuspídea grave fue del 5,0%. Los factores de riesgo asociados a la persistencia/recurrencia de insuficiencia tricuspídea significativa fueron: hipertensión pulmonar grave en el seguimiento (OR 337,91; IC 95%: 34,60-3.300,07; p

Aims: Single nucleotide polymorphisms on chromosome 4q25 have been associated with risk of atrial fibrillation (AF) but the exiguous knowledge of the mechanistic links between these risk variants and underlying electrophysiological alterations hampers their clinical utility. Here, we here tested the hypothesis that 4q25 risk variants cause alterations in the intracellular calcium homeostasis that predispose to spontaneous electrical activity. Methods and results: Western blotting, confocal calcium imaging, and patch-clamp techniques were used to identify mechanisms linking the 4q25 risk variants rs2200733T and rs13143308T to defects in the calcium homeostasis in human atrial myocytes. Our findings revealed that the rs13143308T variant was more frequent in patients with AF and that myocytes from carriers of this variant had a significantly higher density of calcium sparks (14.1±4.5 vs. 3.1±1.3 events/min, p¿=¿0.02), frequency of transient inward (ITI) currents (1.33±0.24 vs. 0.26±0.09 events/min, p¿, This work was supported by multi-centric grants from Centro Nacional de Investigaciones Cardiovasculares [CNIC-2009-08 to L.H.-M. and D.F.]; a grant from Fundacio´ Marato´ TV3 [2015-20-30 to L.H.-M.]; and grants from the Spanish Ministry of Economy and Competition [SAF2014-58286-C2-1-R to L.H.-M.] and [DPI2013-44584-R to R.B.]; and from the Spanish Ministry of Health and Consume, Instituto de Salud Carlos III, Red de Investigacio´n Cardiovascular [RD12/0042/0002] and CIBERCV to J.C., and from Fondo Europeo de Desarrollo Regional (FEDER).

AimsQuantitative real-time RT-PCR (RT-qPCR) has become the method of choice for mRNA quantification, but requires an accurate normalization based on the use of reference genes showing invariant expression across various pathological conditions. Only few data exist on appropriate reference genes for the human heart. The objective of this study was to determine a set of suitable reference genes in human atrial and ventricular tissues, from right and left cavities in control and in cardiac diseases.Methods and resultsWe assessed the expression of 16 reference genes (ACTB, B2M, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, POLR2A, PPIA, RPLP0, TBP, TFRC, UBC, YWHAZ, 18S) in tissues from: right and left ventricles from healthy controls and heart failure (HF) patients; right-atrial tissue from patients in sinus rhythm with (SRd) or without (SRnd) atrial dilatation, patients with paroxysmal (pAF) or chronic (cAF) atrial fibrillation or with HF; and left-atrial tissue from patients in SR or cAF. Consensual analysis (by geNorm and Normfinder algorithms, BestKeeper software tool and comparative delta-Ct method) of the variability scores obtained for each reference gene expression shows that the most stably expressed genes are: GAPDH, GUSB, IPO8, POLR2A, and YWHAZ when comparing either right and left ventricle or ventricle from healthy controls and HF patients; GAPDH, IPO8, POLR2A, PPIA, and RPLP0 when comparing either right and left atrium or right atria from all pathological groups. ACTB, TBP, TFRC, and 18S genes were identified as the least stable.ConclusionsThe overall most stable reference genes across different heart cavities and disease conditions were GAPDH, IPO8, POLR2A and PPIA. YWHAZ or GUSB could be added to this set for some specific experiments. This study should provide useful guidelines for reference gene selection in RT-qPCR studies in human heart.

Background Surgical treatment of active prosthetic aortic valve endocarditis presents a challenge for cardiac surgeons because of tissue friability and destruction caused by infection. Sutureless prostheses, such as the Perceval S (LivaNova, Saluggia, Italy), have emerged as an option among the different surgical approaches for these complicated cases. Methods This study presents data from 9 patients who underwent aortic valve re-replacement with the Perceval S because of active prosthetic aortic valve endocarditis between January 2014 and August 2016. Hemodynamic performance (mean transprosthetic gradient and type of aortic regurgitation) was assessed intraoperatively after weaning from cardiopulmonary bypass, at discharge, and to 6 months postoperatively. Results After weaning from cardiopulmonary bypass, cases 1 and 3 through 6 had no or trivial aortic regurgitation, cases 7 and 8 presented with trivial to mild regurgitation, case 9 showed mild intraprosthetic regurgitation, and case 2 had mild periprosthetic regurgitation. Cases 4 and 7 died of septic shock and multiorgan failure in the perioperative period. In the remaining patients, severity of aortic regurgitation maintained practically invariable at discharge compared with intraoperative results. These 7 patients did well at 6-month follow-up, with good clinical and hemodynamic performance of the Perceval S prosthesis. The median of mean transprosthetic gradient was 11 mm Hg (interquartile range: 10 to 12 mm Hg). Only patient 2 showed mild periprosthetic regurgitation; patient 9 showed mild intraprosthetic insufficiency, and the remaining patients had no or trivial regurgitation. Conclusions The sutureless Perceval S valve is a reasonable alternative for surgical treatment of prosthetic aortic valve endocarditis.

Objective: Life expectancy of patients with congenital heart disease has improved over the past decades, increasing the need for a durable pulmonary prosthetic valve. Biological valves in various forms have become the valve of choice for pulmonary valve replacement (PVR), but structural valve deterioration is unavoidable in the long term. Use of a mechanical valve could be an alternative, but data on long-term outcomes are sparse.Methods: We retrospectively collected and analyzed data on 364 patients with mechanical valves implanted in the pulmonary position between 1965 and 2014. The data originate from medical centers in Barcelona (Spain), Graz (Austria), Groningen (the Netherlands), Munich (Germany), Rochester (United States), Seoul (Republic of Korea), and Tehran (Iran).Results: Median follow-up duration was 4.26 years (range, 0-27 years), mean age at implantation was 27.16 +/- 12.2 years. Tetralogy of Fallot was the most common primary cardiac diagnosis, with a subgroup of 69.8%. Freedom from valvular thrombosis was 91% (95% confidence interval [CI], 87%-94%) at 5 years and 86% (95% CI, 81%-91%) at 10 years post-PVR. With a success rate up to 88%, thrombolysis was a successful therapy. Freedom from reoperation was 97% (95% CI, 94%-99%) at 5 years post-PVR and 91% (95% CI, 85%95%) at 10 years.Conclusions: Mechanical PVR is associated with a limited risk of valvular thrombosis. Thrombolysis was an effective treatment in the majority.