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Abnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and the heart. The bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, but whether cardiovascular disease affects the hematopoietic organ’s microvasculature is unknown. Here we show that hypertension, atherosclerosis and myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis and angiogenesis in the bone marrow, altogether leading to overproduction of inflammatory myeloid cells and systemic leukocytosis. Limiting angiogenesis with endothelial deletion of Vegfr2 (encoding vascular endothelial growth factor (VEGF) receptor 2) curbed emergency hematopoiesis after MI. We noted that bone marrow endothelial cells assumed inflammatory transcriptional phenotypes in all examined stages of cardiovascular disease. Endothelial deletion of Il6 or Vcan (encoding versican), genes shown to be highly expressed in mice with atherosclerosis or MI, reduced hematopoiesis and systemic myeloid cell numbers in these conditions. Our findings establish that cardiovascular disease remodels the vascular bone marrow niche, stimulating hematopoiesis and production of inflammatory leukocytes.

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.

Mechanical complications confer a dreadful prognosis in ST-elevation myocardial infarction (STEMI). Their prevalence and prognosis are not well-defined in the current era of primary percutaneous coronary intervention (pPCI) reperfusion networks. We aimed to analyze prevalence and mortality trends of post-STEMI mechanical complications over 2 decades, before and after the establishment of pPCI networks.Prospective, consecutive registry of STEMI patients within a region of 850 000 inhabitants over 2 decades: a pre-pPCI period (1990-2000) and a pPCI period (2007-2017). We analyzed the prevalence of mechanical complications, including ventricular septal rupture, papillary muscle rupture, and free wall rupture (FWR). Twenty eight-day and 1-year mortality trends were compared between the 2 studied decades.A total of 6033 STEMI patients were included (pre-pPCI period, n=2250; pPCI period, n=3783). Reperfusion was supported by thrombolysis in the pre-pPCI period (99.1%) and by pPCI in in the pPCI period (95.7%). Mechanical complications developed in 135 patients (2.2%): ventricular septal rupture in 38 patients, papillary muscle rupture in 24, and FWR in 73 patients. FWR showed a relative reduction of 60% in the pPCI period (0.8% vs 2.0%, P.001), without significant interperiod changes in the other mechanical complications. After multivariate adjustment, FWR remained higher in the pre-pPCI period (OR, 1.93; 95%CI, 1.10-3.41; P=.023). At 28 days and 1 year, mortality showed no significant changes in all the mechanical complications studied.The establishment of regional pPCI networks has modified the landscape of mechanical complications in STEMI. FWR is less frequent in the pPCI era, likely due to reduced transmural infarcts.

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

OBJECTIVES This study reports long-term clinical outcomes—up to 17 years—among patients undergoing mitral valve replacement with the On-X bileaflet mechanical valve. Prior data regarding long-term outcomes with the On-X mitral valve have been limited. METHODS This retrospective observational study included all patients who underwent mitral valve replacement with the On-X (Standard or Conform-X) valve at 2 major Spanish cardiac surgery centres between 2001 and 2018. The primary study end point was freedom from death. The secondary study end points included surgical mortality and freedom from any valve-related events. Data were obtained from an institutional database, medical records review, direct telephone interviews or the Spanish population registry. Statistical and Kaplan–Meier analyses were performed. RESULTS A total of 661 patients (mean age 63.1 ± 10.9 years, 63% female) were followed for a mean of 5.6 years (range, 0–17.4 years). Survival at 5, 10 and 15 years was 85%, 71% and 63%, respectively. Surgical mortality was 7.3% (48/661). The linearized rate of global mortality was 1.3% patient-year. Freedom from reoperation was 97%, 95% and 92% at 5, 10 and 15 years, respectively; freedom from anticoagulation-related events was 94%, 89% and 89%, respectively. Multivariable analysis showed that mortality increased with total length of stay, age, smoking history, severe pulmonary hypertension and a permanent pacemaker. Patients who received the On-X 25 -mm valve had decreased long-term survival relative to patients who received other On-X valve sizes, possibly due to underlying risk factors. CONCLUSIONS Patients in this study showed good long-term survival and freedom from valve-related events.

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 7.3s (SD 1.9). Morbidity at discharge, 6 m and 1 year was 51%, 14% and 28%. Mortality 4%. Survival at 6m/ 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 seconds 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.

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.

OBJECTIVES Both off-pump coronary artery bypass grafting surgery (OPCABG) and mini-extracorporeal circulation (MECC) have been associated with lower morbidity and mortality and less inflammation than conventional cardiopulmonary bypass. However, studies comparing the 2 techniques are scarce and the results are controversial. We compared the clinical outcomes and inflammatory response of low-risk patients undergoing coronary bypass grafting with MECC versus OPCABG. METHODS We conducted a prospective, randomized study in patients undergoing coronary heart surgery. Two hundred and thirty consecutive low-risk patients were randomly assigned to either receive OPCABG (n = 117) or MECC (n = 113). Clinical outcomes and postoperative biochemical results were analysed in both groups. We also analysed 19 circulating inflammatory markers in a subgroup of 40 patients at 4 perioperative time points. The area under the curve for each marker was calculated to monitor differences in the inflammatory response. RESULTS No significant differences were found between groups regarding perioperative clinical complications and no deaths occurred during the trial. Plasma levels in 9 of the 19 inflammatory markers were undetectable or showed no temporal variation, 3 were higher in the MECC group [interleukin (IL)-10, macrophage inflammatory protein-1β and epidermal growth factor] and 7 were higher in the OPCABG group (growth regulator oncogene, IL-6, IL-8, soluble CD40 ligand, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3 and tumour necrosis factor-α). Differences in 2 proinflammatory cytokines, IL-6 and monocyte chemoattractant protein 1, between the 2 surgical procedures were statistically significant. CONCLUSIONS No clinical differences were observed between in low-risk patients undergoing MECC or OPCABG surgery, but OPCABG was associated with an increased release of proinflammatory cytokines compared with MECC. Studies in larger cohorts and in patients at higher risk are needed to confirm these findings. Clinical trial registration number NCT02118025.

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.

Heparin-induced thrombopenia is a common autoimmune complication. It is a prothrombotic state due to the formation of antibodies against heparin/platelet factor 4 complexes. In this situation drugs other than heparin must be used for anticoagulation during extracorporeal circulation (bypass) surgery. Two cases of heart transplantation are presented in whom bivalirudin was used as an anticoagulant during the cardiopulmonary bypass. Severe bleeding complications were observed in both patients. The diagnosis of heparin-induced thrombopenia needs to be improved, as well as the development of protocols for using new drugs other than heparin. For this reason, we have reviewed current protocols and alternative therapies to heparin.

Debido a la evolucion de la cirugia cardiaca y la cardiologia, los pacientes pediatricos que antano fallecian a causa de cardiopatias congenitas actualmente llegan a la edad adulta. Los pacientes con transposicion de grandes vasos y reparacion fisiologica en el seguimiento pueden evolucionar hacia la insuficiencia cardiaca, como consecuencia del fallo progresivo del ventriculo derecho en posicion sistemica. En esta situacion, el trasplante cardiaco aparece como una posible alternativa terapeutica. Las alteraciones anatomicas y la presencia de conductos intraauriculares hacen que el trasplante precise de una serie de variaciones tecnicas. Presentamos la experiencia en nuestro centro. Entre 1992 y 2004 se han realizado cuatro trasplantes cardiacos en transposicion de grandes vasos y correccion fisiologica. No hubo mortalidad quirurgica. Durante el seguimiento (media, 75 meses), se produjo una muerte por rechazo cronico. Los demas pacientes presentan clase I de la NYHA, con injerto normofuncionante.

Thanks to progress in cardiac surgery and cardiology, pediatric patients with complex congenital heart conditions who would previously have died are now reaching adulthood. Patients with transposition of the great arteries who have undergone atrial repair can present during follow-up with progression towards heart failure as a result of progressive systemic right ventricular failure. In this situation, heart transplantation is a possible therapeutic option. Anatomic abnormalities and the presence of intraatrial conduits ensure that transplantation must involve a number of technical modifications. Here, we present our experience during 1992-2004 with heart transplantations in four patients with transposition of the great arteries and atrial repair. There was no operative mortality. During follow-up (mean period, 75 months), there was one death due to chronic rejection. The other patients remain in New York Heart Association class I, with normally functioning grafts.

La hidatidosis es una enfermedad parasitaria producida por la larva del cestodo Echinococcus. El quiste hidatídico, la forma más habitual de presentación, es producida por la especie E. granulosus. la afectación cardíaca es muy rara, produciéndose en aproximadamente el 0,5–2% de los casos. El 65% de los casos de hidatidosis cardíaca se localizan en las cavidades izquierdas. Presentamos el caso de un paciente en el que la primera localización de la enfermedad fue la aurícula derecha (Ad), junto con diseminación pulmonar quística. La localización exclusiva en las cavidades cardíacas derechas y en la arteria pulmonar constituye una presentación clínica inusual. se ha revisado la bibliografía, prestando especial interés en la importancia de las técnicas de imagen disponibles en la actualidad para su diagnóstico, así como la necesidad de un tratamiento quirúrgico precoz para evitar sus posibles complicaciones.Echinococcosis is a human parasitic disease caused by the larval stage of the cestode Echinococcus. Hydatid cyst, the most frequent presentation, is caused by the species E. granulosus. Cardiac involvement of echinococcosis is infrequent and occurs in approximately 0.5–2% of all cases. 65% of cardiac hydatid cysts are located in the left ventricle and interventricular septum. We present a case of primary cardiac hydatid disease with involvement of the right atrium and pulmonary hydatid embolism. the location of the cyst in the right chambers and pulmonary artery is unusual. We emphasize the value of imaging techniques in the evaluation of the extent of echinococcal lesions and the importance of surgical treatment to avoid major complications.

Resumen Introduccion Los tumores productores de mucina suponen el 1% de los tumores malignos pancreaticos. Entre estos destacan las neoplasias papilares intraductales mucinosas (NPIM) debido a su comportamiento clinico variable, a su mayor frecuencia y a la controversia sobre el tratamiento idoneo y los metodos diagnosticos. El objetivo de este estudio es analizar las caracteristicas epidemiologicas, clinicas y patologicas, los metodos diagnosticos, el tratamiento y la supervivencia de una serie de pacientes con NPIM del pancreas. Pacientes y metodo Se revisaron las NPIM del pancreas diagnosticadas entre 1996-2001. Se recogieron las caracteristicas epidemiologicas, la forma de presentacion, la localizacion pancreatica, los metodos diagnosticos, el tratamiento y la supervivencia. Resultados Se estudio a 8 pacientes con una edad media de 65 anos. La forma de presentacion mas frecuente fue el dolor abdominal y la localizacion mas habitual, la cabeza pancreatica. Los metodos diagnosticos mas empleados fueron la tomografia computarizada (TC) abdominal, la colangiopancreatografia retrograda endoscopica y la determinacion del CA-19.9. Se practicaron 7 resecciones y 1 caso no fue intervenido. Tras un seguimiento medio de 38 meses, la supervivencia es del 75% y la recidiva del 25%. Conclusion La NPIM suele aparecer despues de los 60 anos y se manifiesta como un dolor en el hemiabdomen superior. En la mayoria de las ocasiones se encuentra localizado en la cabeza del pancreas; la TC es la prueba diagnostica mas empleada y la escision quirurgica realizada de forma precoz es el tratamiento mas utilizado. El pronostico es bueno tras la reseccion completa, con supervivencias del 60-70% a los 5 anos.

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.

A 38-year-old woman presented with acute coronary syndrome 9 days postpartum. Coronary catheterization showed an intramural hematoma of the left main artery (LM) and the left anterior descending artery (LAD). During angiography, dissection of the LM, with involvement of the LAD and circumflex artery occurred. The patient presented unstable hemodynamic status. After resuscitation, intra-aortic balloon pump was inserted. The patient underwent two-vessel off-pump surgical revascularization. She was discharged 10 days later.

Aortic valve replacement by bioprosthesis is increasingly being used. Among these, stentless bioprosthesis is becoming a valid choice due to its potential hemodynamic improvement. The Sorin Freedom SOLO stentless aortic valve (FS) (Sorin Biomedica Cardio, Saluggia, Italy) is widely used, with initial and midterm promising results. It is designed to be deployed in a straightforward manner in the supraannular position with a single running suture due to its reproducible implantation technique. Few specific valve-related complications, such as transient thrombocytopenia or rare thrombotic events, are known. Our experience, after the implantation of 33 Freedom SOLO, suggests that using the classical implantation technique, the noncoronary sinus adopts a conformation that increases the difficulty of the implant. Besides, it could also be distorted increasing the risk of periprosthetic leakage and hypothetically becoming the origin of thrombus. We present an easy and safe variation in the implantation technique of the FS that decreases the technical difficulty of the implantation, reduces the risk of periprosthetic leakage, and may additionally reduce the risk of thrombosis. (C) 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Objetivos Comparar dos tecnicas quirurgicas de revascularizacion miocardica: cirugia sin circulacion extracorporea (SCEC) y cirugia con minicirculacion extracorporea (MCEC). Material y metodos Estudio prospectivo y aleatorizado en 230 pacientes intervenidos de cirugia de revascularizacion miocardica. Tras el proceso de aleatorizacion 117 pacientes fueron asignados al grupo SCEC y 113 al grupo MCEC. Se recogieron y compararon sus caracteristicas demograficas, variables preoperatorias clinicas, datos quirurgicos, datos hematologicos y complicaciones postoperatorias. Resultados Las caracteristicas demograficas, las variables preoperatorias clinicas y los datos quirurgicos no presentaron diferencias estadisticamente significativas. Se empleo la arteria mamaria interna en el 97% de los pacientes SCEC y en el 98% de los pacientes MCEC. El numero de anastomosis distales fue de 2,78 vs 2,84; p 0,5 (SCEC vs MCEC). Las cifras de hematocrito y hemoglobina presentaron diferencias estadisticamente significativas a las 24 y 48 h postoperatorias (hematocrito medio: 30,1 vs 29%; p 0,04, y 29,8 vs 28%; p 0,001) (hemoglobina media: 99,9 g/1 vs 95,4 g/1; p 0,005, y 98,6 g/1 vs 93,4 g/1; p vs MCEC, respectivamente). La tasa de transfusion fue comparable entre ambos grupos (57 vs 61%; p 0,5, SCEC vs MCEC, respectivamente). En cuanto a las complicaciones postoperatorias, no se encontraron diferencias en la aparicion de insuficiencia renal, infarto, inestabilidad hemodinamica y fibrilacion auricular. No se produjo ningun caso de mortalidad en ninguno de los dos grupos estudiados. Conclusiones La cirugia de revascularizacion miocardica MCEC es un procedimiento seguro y eficaz, presentando unos resultados semejantes a los obtenidos con la SCEC.

Objectives: Assessment of the long term outcome of mechanical valve prosthesis at pulmonary position in a population of grown-up congenital heart disease patients from a tertiary referral center. Methods: From 1977 to 2007, 22 consecutive patients underwent a total of 25 pulmonary valve replacements with mechanical prosthesis. The most frequent underlying cardiac condition was tetralogy of Fallot (n=16, 64%) and the mean age at the time of pulmonary valve replacement was 32 +/- 11 years (range 14-50 years). Results: The postoperative mortality rate was 4% (n=1) with no late deaths documented after a mean follow-up of 7.6 +/- 7.6 years (range 0.29-24 years). No major bleeding episodes occurred. Three patients presented with valve thrombosis in the setting of long term anticoagulation withdrawal and required valve re-replacement. Two of these patients, both with poor right ventricular function and overt clinical signs of right heart failure at the time of valve re-replacement, experienced further episodes of thrombosis despite correct anticoagulation. All episodes resolved with thrombolysis. After addition of antiplatelet treatment in one case and anticoagulation self-control, in the other, no further thrombosis has been documented. Conclusions: Mechanical valve prosthesis may be an alternative to tissue valve prosthesis in patients with congenital heart disease requiring pulmonary valve replacement. Optimal anticoagulation is crucial and additional antiplatelet treatment should be considered. Our data also suggest that patients with severe right ventricular dysfunction and congestive heart failure might be at particular risk for valve thrombosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Non-penetrating cardiac traumatisms can cause cardiac rupture, myocardial contusion or, rarely, commotio cordis. In cases of rupture of a cardiac cavity, acute and severe cardiac tamponade almost invariably occurs. This paper presents an exceptionally unusual case of non-penetrating cardiac trauma resulting in right atrium rupture contained by the pericardial cavity. A situation of exceptional hemodynamic balance was established with subacute, progressive cardiac tamponade that evolved during three months, presenting gradual right-heart failure instead of the expected acute and severe cardiac tamponade. The rupture of the atrium was successfully repaired.

Orthotopic heart transplantation has become standard treatment for end-stage cardiomyopathy, but experience with this technique for complex congenital heart diseases is limited. We report a patient with visceroatrial situs invs, transposition of the great arteries and previous Mustard correction, who successfully underwent orthotopic heart transplantation.

Mucin-producing pancreatic tumors account for 1% of all malignant tumors of the pancreas. Notable among these are intraductal papillary mucinous neoplasms of the pancreas, due to their variable clinical behavior, increased frequency, and the controversy surrounding the most suitable treatment and diagnostic methods. The aim of this study was to analyze the clinical presentation, epidemiological and pathological features, diagnostic methods, treatment and survival rates of these tumors.We performed a prospective review of patients with a diagnosis of intraductal papillary mucinous neoplasm of the pancreas between 1996 and 2001. Demographic and clinical characteristics, diagnostic tests, surgical treatment, tumor characteristics and survival rates were studied.There were 8 patients. The mean age was 65 years. The most common clinical presentation was abdominal pain. The most frequent localization was the pancreatic head. The most common diagnostic methods used were abdominal computed tomography, endoscopic retrograde pancreatography, and serum CA 19.9 levels. Seven patients underwent pancreatic resection and only one patient was not surgically treated. The mean follow-up period was 38 months with a survival rate of 75% and a recurrence rate of 25%.Intraductal papillary mucinous neoplasms of the pancreas generally appear in the sixth decade of life. The most common presenting symptom is abdominal pain. These neoplasms typically occur in the head of the pancreas. The most commonly used diagnostic test is computed tomography and the main treatment is early surgical resection. The prognosis is good after complete resection, with a 5-year survival rate of 60-70%.

Objetivos Comparar los resultados (prevalencia de complicaciones, estancia hospitalaria y coste economico) entre el nuevo circuito ambulatorio y el circuito antiguo con ingreso para pacientes tributarios a implante de marcapasos de forma electiva. Material y metodos Desde enero de 2008 - mayo de 2012 se recogieron los datos de los pacientes intervenidos de forma electiva (remitidos desde el dispensario de arritmias) de implantacion de marcapasos definitivo y se dividieron en dos grupos: grupo 1, circuito antiguo (dos noches de ingreso) y grupo 2, nuevo circuito ambulatorio (sin ingreso). Resultados Disminucion de la estancia hospitalaria, de la lista de espera y del coste economico en el nuevo circuito ambulatorio, sin hallarse diferencia significativa en la prevalencia de complicaciones comparado con los marcapasos implantados de forma electiva con ingreso. Conclusiones El circuito ambulatorio a traves de cirugia sin ingreso para implantacion de marcapasos electivos es un modelo seguro, eficaz y mas barato.

A 39-year-old man with no clinical relevant data, elite long-distance runner, was admitted to our institution with the diagnosis of ventricular fibrillation while participating in a half-marathon competition. He was resuscitated at the site of the event with electrical cardioversion, and at his admission, he was clinically stable. Electrocardiogram demonstrated regular …

3 68-year-old man was admitted to our hospital with a history of dyspnea and considerable fatigue with xercise. Transthoracic echocardiography showed severe itral, aortic, and tricuspid regurgitation. The patient nderwent coronary angiography before surgery, which evealed a giant coronary artery fistula arising from the ircumflex artery (Fig 1). A multi-sliced computed tomoraphic scan was performed to delineate the fistula and ocalize its drainage. Three-dimensional reconstruction howed a tortuous course with multiple loops in the ateral wall (Fig 2) that seemed to end in the pulmonary rtery. Intravenous contrast enhancement allowed the ocation of the drainage orifice in the superior vena cava, ear the right atrium. The patient was operated on through a midline ternotomy. On opening the pericardium, the dilated essel (arrow) was seen to course from the lateral wall f the left ventricle through the transverse sinus, and it nished at the superior vena cava (Fig 3). It measured 5 mm in diameter. Cardiopulmonary bypass was stablished (with bi-caval cannulation) after occlusion f the fistula near its drainage. After mitral valve epair, aortic valve replacement, and tricuspid ring nnuloplasty, the superior vena cava was opened and