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1.
Eur J Immunol ; 53(7): e2250097, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37119053

RESUMEN

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart-transplanted patients were collected before (pre-), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4+ or CD8+ T cells and CD56dim CD16+ NK cells immediately after HTx linked to a decrease in naïve CD8+ and CM CD4+ T as well as CD56bright CD16- NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69+ CD25- and diminished CD69- CD25- CD4+ or CD8+ T-cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo-specific immune responses.


Asunto(s)
Linfocitos T CD8-positivos , Trasplante de Corazón , Humanos , Células Asesinas Naturales , Subgrupos Linfocitarios , Inmunofenotipificación , Antígeno CD56/metabolismo
2.
Am J Transplant ; 22(8): 2064-2076, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35426974

RESUMEN

Heart transplantation across preformed donor-specific HLA-antibody barriers is associated with impaired short- and long-term survival. Therefore, in recipients with preformed anti-HLA antibodies, waiting for crossmatch-negative donors is standard practice. As an alternative strategy, recipients with preformed anti-HLA donor specific antibodies have been managed at our institutions with a perioperative desensitization regimen. A retrospective analysis was performed comparing heart transplant recipients with preformed donor-specific HLA-antibodies to recipients without donor-specific antibodies. Recipients with a positive virtual crossmatch received a perioperative desensitization protocol including tocilizumab intraoperatively, plasma exchange and rituximab followed by a six-month course of IgGAM. Among the 117 heart-transplanted patients, 19 (16%) patients underwent perioperative desensitization, and the remaining 98 (84%) patients did not. Cold ischemic time, posttransplant extracorporeal life support for primary graft dysfunction, and intensive care unit stay time did not differ between groups. At 1-year follow-up, freedom from pulsed steroid therapy for presumed rejection and biopsy-confirmed acute cellular or humoral rejection did not differ between groups. One-year survival amounted to 94.7% in the treated patients and 81.4% in the control group. Therefore, heart transplantation in sensitized recipients undergoing a perioperative desensitization appears safe with comparable postoperative outcomes as patients with a negative crossmatch.


Asunto(s)
Trasplante de Corazón , Trasplante de Riñón , Anticuerpos , Suero Antilinfocítico , Desensibilización Inmunológica/métodos , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Antígenos HLA , Prueba de Histocompatibilidad/métodos , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos
3.
Cytokine ; 149: 155744, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34649160

RESUMEN

BACKGROUND: Ischemia/reperfusion injury (IRI) is associated with inflammatory responses contributing to the development of primary graft dysfunction (PGD) and rejection. Here, we investigated the pathophysiology of IRI and the early phase after heart transplantation (HTx) regarding its cytokine/chemokine and endothelial networks. METHODS: Using multiplex technology, we assessed protein concentrations in plasma samples of HTx recipients (n = 11) pre-, postoperatively, 24 h and 3 weeks after HTx. The same proteins were quantified in organ storage solutions at the end of heart storage (n = 10). Unsupervised cluster, principal component analysis (PCA), K-nearest neighbor (KNN) network classifier analysis, ANOVA and Spearman correlation analyses were performed to identify specific patterns for IRI and individual kinetics of important soluble factors in HTx. RESULTS: Unique patterns of soluble factors were identified in plasma of HTx patients. KNN analysis defined IL-10, IL-6, sIL-6Rα, IL-1RA, IL-16, sVEGFR-1, IGFBP-1, HGF and sHer-2 as strongest signals directly post-Tx declining 24 hrs after HTx. By contrast, MIF, osteopontin (OPN), sVCAM-1 and sICAM-1, IGFBP-1, SCGF-ß, HGF were highly enriched in organ storage solutions, reflecting distinct ischemic (storage solution) vs. reperfusion (plasma) signatures. CONCLUSIONS: We identified specific inflammatory signatures for ischemic vs. reperfusion phases of HTx, associated with pro- as well as anti-inflammatory and endothelial biomarker candidates for IRI. These signatures might help to identify potential danger factors and their networks at both the ex situ (ischemic) as well as the reperfusion phase in the recipient after implantation.


Asunto(s)
Biomarcadores/metabolismo , Isquemia/metabolismo , Daño por Reperfusión/metabolismo , Adolescente , Adulto , Quimiocinas/metabolismo , Niño , Citocinas/metabolismo , Femenino , Trasplante de Corazón/métodos , Humanos , Masculino , Persona de Mediana Edad , Reperfusión/métodos , Adulto Joven
4.
Thorac Cardiovasc Surg ; 70(6): 482-492, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35235989

RESUMEN

OBJECTIVES: The aim of this study was to analyze our 10-year experience with the HVAD in a real-world scenario in a high-volume German heart center. METHODS: We retrospectively analyzed outcomes of adults (≥18 years) with terminal heart failure (HF), who underwent HVAD implantation for durable LVAD therapy in our center between October 2009 and March 2020. Primary and secondary end points were all-cause death after implantation and LVAD-associated complications, respectively. We focused the distinct analyses on risk profiles at the time of implantation and implant strategies, i.e., bridge-to-transplant (BTT) or destination therapy (DT). RESULTS: A total of 510 patients were included, with 229 and 281 individuals in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level 1 (45%) and 2 to 4, respectively. Median follow-up was 26 months (IQR: 5-54 months). Overall survival at 1, 3, and 5 years after HVAD implantation was 66% (95% CI; 61.7-70%), 49.4% (95% CI; 44.9-53.8%), and 37.4% (95% CI; 32.8-42%), not censored for LVAD exchange, LVAD explantation, or heart transplantation. INTERMACS level 1 and peri-operative temporary right heart assistance were independent risk factors for survival. Survival was best in BTT patients undergoing heart transplantation at any time during follow-up. The INTERMACS level at time of HVAD implantation did not affect survival after heart transplantation. Freedom from the combined end point of any device-associated severe complication and death was 44.5% (95% CI; 40-48.8%) at 1-year after implantation. CONCLUSION: The HVAD is a reliable pump for durable mechanical circulatory support even in high-risk patients. Still, heart transplantation outperforms durable MCS therapy for a superior long-term survival.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Adulto , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Trasplante de Corazón/efectos adversos , Corazón Auxiliar/efectos adversos , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
5.
Artif Organs ; 45(7): 736-741, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33432621

RESUMEN

The purpose of the study was to investigate the outcome of secondary surgical aortic valve replacement (sSAVR) in patients with severe aortic regurgitation (AR) in the context of ventricular assist device (VAD) therapy. From 2009 to 2020, 792 patients underwent cf-LVAD implantation [HVAD (Medtronic, USA), n = 585, and HM 3 (Abbott, USA), n = 207]. All cf-LVAD patients with severe AR requiring secondary AVR were enrolled in this study. A total of six patients (median, 40 years, IQR; 34-61 years, 50% male) underwent secondary surgical aortic valve replacement (sSAVR) after cf-LVAD implantation. Median time of previous LVAD support was 26 months (IQR: 21-29 months). Two patients required additional tricuspid valve repair (TVR) and one patient underwent SAVR after failed TAVR. Four patients needed temporary right ventricular assist device (RVAD) with a median of 30 days (IQR; 29-33 days). Three patients were bridged to urgent heart transplantation due to persevering right heart failure, whereas two destination therapy (DT) candidates survived without any associated complications. An additional DT patient died of pneumonia 1 month after sSAVR. Secondary surgical aortic valve replacement in ongoing LVAD patients is an advanced procedure for a complex cohort. In our series, sSAVR was safely performed and effective, but involved a high-risk for subsequent right heart failure, requiring urgent heart transplantation. In LVAD patients with severe AR requiring treatment where TAVR is not feasible, sSAVR can be evaluated as salvage option for bridge to transplant patients or selected destination therapy candidates.


Asunto(s)
Insuficiencia de la Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas , Corazón Auxiliar , Adulto , Femenino , Trasplante de Corazón , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Válvula Tricúspide/cirugía
6.
Artif Organs ; 45(5): 473-478, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33141976

RESUMEN

Effects of cranioplasty (CP) and skullcap reimplantation after decompressive craniectomy (DC) for cerebral hemorrhage or malignant brain infarction in patients with left ventricular assist device (LVAD) support as bridge to transplantation has not been surveyed yet. The aim of this study was to evaluate outcome and management after CP when aiming for transplantation. Data were collected from our prospective institutional database including all patients undergoing LVAD implantation between 2010 and 2019. Six patients needed CP procedures and were included. Our analysis focused on postoperative outcome, survival, and facilitation of heart transplantation. Study endpoints included also all-cause mortality. From a total of 1010 LVAD implantations during analysis period in our center, six bridge-to-transplantation LVAD patients [median age at LVAD implantation: 32.5 years (IQR: 24.8-39.5 years); four male, HVAD, n = 3; HM II, n = 1; HM 3, n = 2] underwent CP with imminent entrapment secondary to cerebral hemorrhage or malignant infarction. Primary heart failure etiology was myocarditis (n = 2), dilated (n = 2), or ischemic (n = 2). Median INTERMACS class was 1.5 (IQR; 1.0-2.8). Median time on LVAD support to DC procedure was 33 months (IQR: 16-48 months). The indication for DC was intraparenchymal hemorrhage (n = 4), subdural hematoma (n = 1), and malignant middle cerebral artery infarction (n = 1). After a median time of 4 months (IQR: 3.3-4.0 months, range; 2.0-10 months) post DC procedure, CP was subsequently performed without profound neurologic disabilities in all patients. After median time of 26 months (IQR: 21-42 months) follow-up, three patients successfully received heart transplantation, one patient could undergo LVAD explantation for myocardial recovery, and the remaining two patients are still on the list awaiting heart transplantation. CP procedure with skullcap reimplantation is feasible and can be safely performed in LVAD patients, which subsequently may even be eligible for heart transplantation with beneficial prognosis.


Asunto(s)
Craniectomía Descompresiva/efectos adversos , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Corazón Auxiliar/efectos adversos , Hemorragias Intracraneales/cirugía , Reimplantación , Adolescente , Adulto , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/mortalidad , Humanos , Hemorragias Intracraneales/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Cráneo/cirugía , Resultado del Tratamiento , Adulto Joven
7.
J Artif Organs ; 24(2): 173-181, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33337536

RESUMEN

BACKGROUND: Redictors of repetitive left-ventricular assist device (LVAD)-thrombosis have not been studied yet. METHODS: We identified predictors of recurrent LVAD thrombosis in HeartWare (HVAD) patients in a long-term study from 2010 until 2020. We included all patients with two or more thrombolysis treatments for repetitive HVAD thrombosis and effectiveness of thrombolytic therapy was defined as freedom from stroke, death, another HVAD thrombosis, or surgical device exchange within 30 days after the event. Study endpoints also include all-cause mortality and heart transplantation. RESULTS: A total of 534 HVAD implantations have been screened, and 73 patients (13.7%) developed first HVAD thrombosis after a median of 10 months (IQR; 6-21 months). 46 of these patients had effective thrombolysis in 71.7% (n = 33/46). After a median of 14 months (IQR 4-32 months) follow-up, 17 patients (51.5%) had developed a second HVAD thrombosis and all were treated with t-PA therapy again, resulting in effectiveness in 76.5% (n = 13/17). The four patients with ineffective t-PA therapy underwent subsequent surgical HVAD exchange. Multiple Cox regression model analysis revealed time interval between HVAD implantation and first thrombosis as an independent risk factor of recurrent thrombosis (HR, 0.93, 95% CI 0.87-0.99, p = 0.031). Kaplan-Meier analysis at 3 year follow-up showed no significant difference in overall survival for recurrent vs non-recurrent thrombosis groups (log-rank test, p = 0.959). CONCLUSION: Recurrent HVAD thrombosis mostly appears within 12 months after first thrombosis. Systemic t-PA therapy for recurrent pump thrombosis seems safe, achieving comparable effectiveness rates to initial t-PA therapy. Survival does not differ between patients with or without recurrent HVAD thrombosis.


Asunto(s)
Fibrinolíticos/uso terapéutico , Corazón Auxiliar/efectos adversos , Trombosis/etiología , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Femenino , Insuficiencia Cardíaca/terapia , Trasplante de Corazón , Corazón Auxiliar/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/prevención & control , Trombosis/tratamiento farmacológico
8.
Artif Organs ; 41(2): 192-199, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27296083

RESUMEN

Myocardial stem cell therapy in heart failure is strongly dependent on successful cellular transfer, engraftment, and survival. Moreover, massive cell loss directly after intramyocardial injection is commonly observed, generating the need for efficient longitudinal monitoring of transplanted cells in order to develop more efficient transplantation techniques. Therefore, the aim of the present study was to assess viability and cardiac retention of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis (BLI) and magnetic resonance imaging (MRI). Murine induced pluripotent stem cells (iPSCs) were transfected for luciferase reporter gene expression and labeled intracellularly with supraparamagnetic iron oxide particles. Consequently, 5 × 105 cells were transplanted intramyocardially following left anterior descending coronary artery ligation in mice. Cardiac iPSCs were detected using BLI and serial T2* sequences by MRI in a 14-day follow-up. Additionally, infarct extension and left ventricular (LV) function were assessed by MRI. Controls received the same surgical procedure without cell injection. MRI sequences showed a strong MRI signal of labeled iPSCs correlating with myocardial late enhancement, demonstrating engraftment in the infarcted area. Mean iPSC volumes were 4.2 ± 0.4 mm3 at Day 0; 3.1 ± 0.4 mm3 at Day 7; and 5.1 ± 0.8 mm3 after 2 weeks. Thoracic BLI radiance decreased directly after injection from 1.0 × 106 ± 4.2 × 104 (p/s/cm2 /sr) to 1.0 × 105 ± 4.9 × 103 (p/s/cm2 /sr) on Day 1. Afterward, BLI radiance increased to 1.1 × 106 ± 4.2 × 104 (p/s/cm2 /sr) 2 weeks after injection. Cardiac graft localization was confirmed by ex vivo BLI analysis and histology. Left ventricular ejection fraction was higher in the iPSC group (30.9 ± 0.9%) compared to infarct controls (24.0 ± 2.1%; P < 0.05). The combination of MRI and BLI assesses stem cell fate in vivo, enabling cardiac graft localization with evaluation of LV function in myocardial infarction.


Asunto(s)
Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/terapia , Corazón/diagnóstico por imagen , Células Madre Pluripotentes Inducidas/trasplante , Animales , Células Cultivadas , Células Madre Pluripotentes Inducidas/citología , Mediciones Luminiscentes/métodos , Imagen por Resonancia Magnética , Ratones , Imagen Multimodal/métodos , Miocardio/patología , Imagen Óptica/métodos
9.
Artif Organs ; 41(3): 272-275, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27087560

RESUMEN

The therapy of terminal heart failure with left ventricular assist devices has become a standard in cardiac surgery. Yet the surgical implantation technique is not standardized and differs from center to center. Complications associated with left ventricular assist device (LVAD) inflow cannula placement are thrombosis, suction events, and flow disturbances. Within this in vitro study we aimed to investigate if the fixation technique of the sewing ring has an impact on the position of the inflow cannula. For this in vitro study the HeartMate III LVAD (Thoratec Corporation, Pleasanton, CA, USA) was used. In five sessions, two approaches were considered for coring of the ventricle for LVAD inflow cannula insertion: "sew-then-core" and "core-then-sew." In the "sew-then-core" technique, the sewing cuff is first affixed to the heart, usually with 8-16 interrupted pledgeted mattress sutures. Subsequently, a cylindrical knife is used to resect a cylindrical core of myocardium to permit cannula insertion. In the "core-then-sew" technique, the sequence is reversed such that the knife is used before the suture ring is affixed. When the "sew-then-core" technique is used, the mattress sutures may be placed with full-thickness bites that penetrate the endocardium (i.e., transmural stitching) or partial-thickness bites that do not penetrate the endocardium (i.e., epicardial stitching). When the "core-then-sew" technique is used, the suture is passed fully into the ventricular lumen and fed back through the cored hole, at which point the needle may be reinserted into the freshly cored myocardium such that it exits the epicardium (i.e., transmural stitching with back stitch) or not (i.e., transmural stitching without back stitch). These four different sewing ring fixation suturing techniques were tested by experienced surgeons to affix the sewing ring: transmural stitching, epicardial stitching, transmural stitching with back stitch, and transmural stitching without back stitch. The sewing ring was sewed onto a silicone dummy designed to simulate the left ventricle with standard 2-0 Ethibond sutures (Ethicon, Somerville, NY, USA). Afterward, the dummies were measured and documented via photography. In addition, porcine hearts were used to simulate the suturing techniques in a physiological setting. The setting of the inflow cannula is substantially influenced by the fixation method of the sewing ring. Epicardial stitching showed the best results with stable cannula fixation, minimal gap around the cannula and no contact between the sutures and sewing ring with blood. The method of transmural stitching without back stitch showed the worst results by creating the biggest epithelial gap between inflow cannula and tissue as well as proving the biggest surface for blood contact between sewing ring and sutures. In general, both "sew-then-core" techniques resulted in a greater degree of apposition between the cuff and epicardial tissue. Within the study we revealed that the surgical fixation of the sewing ring has a significant impact on the inflow cannula stability, position, and tissue apposition in LVAD implantation surgery. Epicardial stitching of the sewing ring provides the best results in order to prevent suction events as well as thrombosis formation.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Catéteres , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos/cirugía , Corazón Auxiliar , Implantación de Prótesis/métodos , Técnicas de Sutura , Función Ventricular Izquierda , Animales , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , Modelos Anatómicos , Modelos Animales , Modelos Cardiovasculares , Diseño de Prótesis , Porcinos
10.
Curr Opin Cardiol ; 31(3): 308-12, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27008371

RESUMEN

PURPOSE OF REVIEW: Ventricular assist device (VAD) therapy is currently one of the fastest-developing fields in cardiac surgery. Consistently improved technology, research, and gain of clinical experience have established VADs as an important option for the treatment of congestive heart failure. During the past year, novel devices and less invasive surgical procedures have been revolutionizing this field. The purpose of this manuscript is to review these innovations with special emphasis on device-related surgery. RECENT FINDINGS: Device miniaturization has enabled less invasive VAD surgery, excluding the need for full sternotomy. Recent data show that intrahospital survival rates following less invasive VAD implantation are surpassing 90%. Secondly, two new devices, Heartmate 3 and MVAD, are being applied and tested for clinical application. In this context, the Heartmate 3 CE mark study recently concluded with excellent outcomes and without any pump thrombosis or device malfunctions. SUMMARY: The first clinical results of the newest generation of VADs are very promising compared with old-generation devices. Furthermore, less invasive surgery is becoming a standard for the implantation, exchange, or explantation of left VADs. The joint venture of improved technology and innovative surgical techniques will push this field forward to even better outcomes and reduced complication rates.


Asunto(s)
Corazón Auxiliar , Implantación de Prótesis/tendencias , Humanos , Implantación de Prótesis/métodos
12.
Artif Organs ; 39(6): 473-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25735454

RESUMEN

The use of mechanical circulatory support to treat patients with congestive heart failure has grown enormously, recently surpassing the number of annual heart transplants worldwide. The current generation of left ventricular assist devices (LVADs), as compared with older devices, is characterized by improved technologies and reduced size. The result is that minimally invasive surgery is now possible for the implantation, explantation, and exchange of LVADs. Minimally invasive procedures improve surgical outcome; for example, they lower the rates of operative complications (such as bleeding or wound infection). The miniaturization of LVADs will continue, so that minimally invasive techniques will be used for most implantations in the future. In this article, we summarize and describe minimally invasive state-of-the-art implantation techniques, with a focus on the most common LVAD systems in adults.


Asunto(s)
Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/métodos , Corazón Auxiliar , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Remoción de Dispositivos , Humanos , Diseño de Prótesis , Resultado del Tratamiento
13.
Artif Organs ; 38(6): 507-10, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24571624

RESUMEN

The new generation of left ventricular assist devices (LVADs) has enabled minimally invasive surgical procedures for implantation. Herein we present two alternative approaches for minimally invasive LVAD explantation following cardiac recovery, avoiding a sternotomy and improving patient safety.


Asunto(s)
Remoción de Dispositivos/métodos , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Función Ventricular Izquierda , Adolescente , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Diseño de Prótesis , Recuperación de la Función , Técnicas de Sutura , Resultado del Tratamiento
14.
Artif Organs ; 38(7): 539-42, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25041282

RESUMEN

The new generation of left ventricular assist devices has enabled minimally invasive surgical procedures. Herein we present a novel technique of left ventricular assist device exchange through a left-sided anterolateral thoracotomy.


Asunto(s)
Remoción de Dispositivos/métodos , Corazón Auxiliar , Toracotomía/métodos , Adolescente , Humanos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos
15.
Artif Organs ; 38(11): 978-84, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24571740

RESUMEN

The limited success of cardiac stem cell therapy has lately generated discussion regarding its effectiveness. We hypothesized that immediate cell loss after intramyocardial injection significantly obscures the regenerative potential of stem cell therapy. Therefore, our aim was to assess the distribution and quantity of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis. In this context, we wanted to investigate if the injection of different cell concentrations would exert influence on cardiac cell retention. Murine-induced pluripotent stem cells were transfected for luciferase reporter gene expression and transplanted into infarcted myocardium in mice after left anterior descending coronary artery ligation. Cells were delivered constantly in aqueous media (15 µL) in different cell concentrations (group A, n = 10, 5.0 × 10(5) cells; group B, n = 10, 1.0 × 10(6) cells). Grafts were detected using bioluminescence imaging. Organ explants were imaged 10 min after injection to quantify early cardiac retention and cell biodistribution. Bioluminescence imaging showed a massive early displacement from the injection site to the pulmonary circulation, leading to lung accumulation. Mean cell counts of explanted organs in group A were 7.51 × 10(4) ± 4.09 × 10(3) (heart), 6.44 × 10(4) ± 2.48 × 10(3) (left lung), and 8.06 × 10(5) ± 3.61 × 10(3) (right lung). Respective cell counts in group B explants were 1.69 × 10(5) ± 7.69 × 10(4) (heart), 2.11 × 10(5) ± 4.58 × 10(3) (left lung), and 3.25 × 10(5) ± 9.35 × 10(3) (right lung). Applying bioluminescence imaging, we could unveil and quantify massive early cardiac stem cell loss and pulmonary cell accumulation following intramyocardial injection. Increased injection concentrations led to much higher intracardiac cell counts; however, pulmonary biodistribution of transplanted cells still persisted. Therefore, we recommend applying tissue engineering techniques for cardiac stem cell transplantations in order to improve cardiac retention and limit biodistribution.


Asunto(s)
Células Madre Pluripotentes Inducidas/trasplante , Infarto del Miocardio/terapia , Animales , Recuento de Células , Células Cultivadas , Inyecciones Intralesiones , Mediciones Luminiscentes , Ratones , Ratones SCID
16.
Rev Med Chil ; 142(7): 914-8, 2014 Jul.
Artículo en Español | MEDLINE | ID: mdl-25378012

RESUMEN

In the last 2 decades, there have been significant advances in medical treatment of heart failure. However, there is a group of patients who are refractory to the available medical therapy and progress inevitably to a state of end-stage heart failure, whose only therapeutic alternative is cardiac transplantation. But this is an option limited by the scarce availability of donors. Therefore many patients die waiting for an organ. Recently, extra or intracorporeal left ventricular devices have emerged as a viable alternative for patients with end-stage heart failure waiting for a heart transplant. These devices discharge the left ventricle, increasing cardiac output and improving systemic perfusion. This year, in our hospital we began a left ventricular device implantation program for the most severely ill patients on the waiting list for cardiac transplantation. We report two males aged 30 and 53 years, in whom a left ventricular device was successfully implanted, using a minimally invasive surgical technique developed at the University of Hannover in Germany.


Asunto(s)
Insuficiencia Cardíaca/cirugía , Corazón Auxiliar , Implantación de Prótesis/métodos , Adulto , Humanos , Masculino , Ilustración Médica , Persona de Mediana Edad , Resultado del Tratamiento
17.
Eur Heart J Case Rep ; 8(4): ytae146, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38660462

RESUMEN

Background: Primary cardiac tumours are rare, accounting for only 0.002-0.03% at autopsy. Cardiac haemangiomas are benign vascular tumours and constitute for 0.28% of all primary cardiac tumours. Cavernous haemangiomas, capillary haemangiomas, and arteriovenous haemangiomas are three distinct types. Cardiac haemangiomas are often misdiagnosed as myxomas and must be differentiated from malignant angiosarcomas. Case summary: We present a 44-year-old Mediterranean male patient with a cavernous haemangioma in the inferior vena cava and right atrium, detected on transthoracic echocardiography. The patient experienced palpitations and dyspnoea on exertion. Computed tomography (CT) angiography revealed a 7.5 × 6 × 5 cm mass suspected to be perfused by the distal right coronary artery. A watch-and-wait approach was suggested, leading to a cardiac magnetic resonance imaging (MRI) with contrast 6 months later. T1 mapping exhibited a prolonged relaxation time and isointensity to the myocardium. T2 mapping revealed a homogenous hyperintense mass with heterogenous late enhancement. Surgical excision was performed using a bicaval cannulation technique on cardiopulmonary bypass. Intraoperatively, no connection to the coronaries was noted. At 1 year follow-up, the patient reported restored physical resilience, with no evidence of tumour recurrence. Discussion: Clinical symptoms of cardiac cavernous haemangiomas are unspecific and become evident once the tumour grows. To investigate the nature and vascular involvement of the tumour, a contrast-enhanced CT angiography or MRI can be performed. Cardiac haemangiomas are often misdiagnosed and must be differentiated from malignant angiosarcomas. Clear guidelines for the treatment of cardiac haemangiomas in adult patients are lacking. Primary cardiac tumours require thorough investigation, and surgical intervention should be tailored to the individual's case.

18.
Intensive Crit Care Nurs ; 84: 103748, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38875775

RESUMEN

OBJECTIVE: We tested the feasibility of a randomized controlled trial for comparing primary nursing with standard care. RESEARCH METHODOLOGY: Elective cardiac surgical patients were eligible for inclusion. Patients with an intensive care unit stay of ≥ 3 days were followed up until intensive care unit discharge. Recruitment period was one year. SETTING: Two intensive care units at a university hospital specialized in cardiovascular and diabetic diseases. MAIN OUTCOME MEASURES: Primary outcomes were recruitment and delivery rate. Primary clinical outcome was duration of delirium, as assessed by the Confusion Assessment Method for Intensive Care Units. Secondary outcomes included the incidence of delirium, anxiety (10-point Numeric Rating Scale), and the satisfaction of patient relatives (validated questionnaire). RESULTS: Of 369 patients screened, 269 could be allocated to primary nursing (n = 134) or standard care (n = 135), of whom 46 patients and 48 patients, respectively, underwent an intensive care unit stay ≥ 3 days. Thus, recruitment and delivery rates were 73 and 26 %, respectively. During primary nursing and standard care, 18 and 24 patients developed a delirium, with a median duration of 32 (IQR: 14-96) and 24 (IQR: 8-44) hours (P = 0.10). The risk difference of delirium for primary nursing versus standard care was 11 % and the relative risk was 0.65 (95 % CI: 0.28-1.46; P = 0.29). The extent of anxiety was similar between groups (P = 0.13). Satisfaction could be assessed in 73.5 % of relatives, without substantial differences between groups. CONCLUSION: Data demonstrate that a trial for comparing primary nursing with standard care is generally feasible. However, the incidence of delirium may be a better primary outcome parameter than delirium duration, both in terms of long-term patient outcome and robustness of data quality. IMPLICATIONS FOR CLINICAL PRACTICE: A randomized clinical trial regarding nursing organization during intensive care unit stay requires detailed planning of patient recruitment, data evaluation, and power calculation.

19.
J Clin Med ; 13(2)2024 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-38256596

RESUMEN

Right heart failure (RHF) is associated with poor outcomes, especially in patients undergoing left ventricular assist device (LVAD) implantation. The aim of this study was to identify predictors of RHF after LVAD implantation. Of 129 consecutive patients (mean age 56 ± 11 years, 89% male) undergoing LVAD implantation, 34 developed RHF. Compared to patients without RHF, those with RHF required longer invasive mechanical ventilation and had longer intensive care unit and hospital stays (p < 0.01). One-year all-cause mortality was significantly higher in patients with versus without RHF after LVAD implantation (29.4% vs. 1.2%; hazard ratio 35.4; 95% confidence interval 4.5-277; p < 0.001). Mortality was highest in patients with delayed RHF after initial LVAD-only implantation (66.7%). Patients who did versus did not develop RHF had significantly higher baseline pulmonary vascular resistance (PVR; 404 ± 375 vs. 234 ± 162 dyn/s/cm5; p = 0.01). PVR > 250 dyn/s/cm5 was a significant predictor of survival in patients with RHF after LVAD implantation. These data confirm the negative impact of RHF on morbidity and mortality after LVAD implantation. Preoperative PVR > 250 dyn/s/cm5 determined using invasive right heart catheterization was an independent predictor of developing RHF after LVAD implantation, and of subsequent mortality, and could be used for risk stratification in the setting for deciding between single or biventricular support strategy.

20.
Front Cardiovasc Med ; 11: 1298466, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38450373

RESUMEN

Objectives: Minimally-invasive direct coronary artery bypass (MIDCAB) is a less-invasive alternative to full sternotomy off-pump coronary artery bypass (FS-OPCAB) revascularization of the left anterior descending artery (LAD). Some studies suggested that MIDCAB is associated with a greater risk of graft occlusion and repeat revascularization than FS-OPCAB LIMA-to-LAD grafting. Data comparing MIDCAB to FS-OPCAB with regard to long-term follow-up is scarce. We compared short- and long-term results of MIDCAB vs. FS-OPCAB revascularization over a maximum follow-up period of 10 years. Patients and methods: From December 2009 to June 2020, 388 elective patients were included in our retrospective study. 229 underwent MIDCAB, and 159 underwent FS-OPCAB LIMA-to-LAD grafting. Inverse probability of treatment weighting (IPTW) was used to adjust for selection bias and to estimate treatment effects on short- and long-term outcomes. IPTW-adjusted Kaplan-Meier estimates by study group were calculated for all-cause mortality, stroke, the risk of repeat revascularization and myocardial infarction up to a maximum follow-up of 10 years. Results: MIDCAB patients had less rethoracotomies (n = 13/3.6% vs. n = 30/8.0%, p = 0.012), fewer transfusions (0.93 units ± 1.83 vs. 1.61 units ± 2.52, p < 0.001), shorter mechanical ventilation time (7.6 ± 4.7 h vs. 12.1 ± 26.4 h, p = 0.005), and needed less hemofiltration (n = 0/0% vs. n = 8/2.4%, p = 0.004). Thirty-day mortality did not differ significantly between the two groups (n = 0/0% vs. n = 3/0.8%, p = 0.25). Long-term outcomes did not differ significantly between study groups. In the FS-OPCAB group, the probability of survival at 1, 5, and 10 years was 98.4%, 87.8%, and 71.7%, respectively. In the MIDCAB group, the corresponding values were 98.4%, 87.7%, and 68.7%, respectively (RR1.24, CI0.87-1.86, p = 0.7). In the FS group, the freedom from stroke at 1, 5, and 10 years was 97.0%, 93.0%, and 93.0%, respectively. In the MIDCAB group, the corresponding values were 98.5%, 96.9%, and 94.3%, respectively (RR0.52, CI0.25-1.09, p = 0.06). Freedom from repeat revascularization at 1, 5, and 10 years in the FS-OPCAB group was 92.2%, 84.7%, and 79.5%, respectively. In the MIDCAB group, the corresponding values were 94.8%, 90.2%, and 81.7%, respectively (RR0.73, CI0.47-1.16, p = 0.22). Conclusion: MIDCAB is a safe and efficacious technique and offers comparable long-term results regarding mortality, stroke, repeat revascularization, and freedom from myocardial infarction when compared to FS-OPCAB.

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