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BACKGROUND: Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown. METHODS: To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders. RESULTS: These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions. CONCLUSIONS: This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.
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Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Humanos , Transcriptoma , Estudios Prospectivos , Fosfopéptidos/metabolismo , Proteómica , Donantes de Tejidos , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismoRESUMEN
OBJECTIVES: The purpose of this study was to define anterior mitral leaflet (AML) length and mitral ring characteristics associated with LVOT obstruction and PVL following MViR. BACKGROUND: Transcatheter Mitral Valve in Ring (MViR) procedural complications including parvalvular leak (PVL) and left ventricular outflow tract (LVOT) obstruction are frequent. METHODS: Clinical records, computer tomographic scans (CTs) and echocardiograms of consecutive MViR patients were retrospectively reviewed for anterior mitral leaflet length, CT-simulated neoLVOT, and aortomitral angle among patients with and without MViR-induced LVOT obstruction. Acute and 1-year outcomes are described. RESULTS: Twenty-two patients underwent MViR. Technical success was achieved in 13/22 (57.1%) patients, limited by paravalvular regurgitation requiring second transcatheter heart valves (THVs) in seven patients. Second valves were needed in 6/11 (54.5%) patients with 3-dimensional rings but 1/11 (9.1%, p = .06) of patients with planar rings. Procedure success at 30 days was achieved in 20/22 (90.9%) patients. There were no procedural, in-hospital, or 30-day deaths. Two patients developed significant LVOT obstruction, one managed with urgent surgery and one with elective alcohol septal ablation. Anterior mitral leaflets were longer among the two patients with LVOT obstruction than the 20 patients who did not develop LVOT obstruction when measured by TEE (30 mm vs. 21 mm, p = .009) or by CT (29 mm vs. 22 mm, p = .026). CONCLUSIONS: AML >25 mm increases the risk of MViR induced LVOT obstruction. PVL is common, particularly in 3-dimensional rings which can be managed with a second THV.
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Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Mitral , Obstrucción del Flujo Ventricular Externo , Cateterismo Cardíaco/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Obstrucción del Flujo Ventricular Externo/etiologíaRESUMEN
BACKGROUND: Reducing preventable hospital readmissions after coronary artery bypass graft (CABG) surgery has become a national priority. Predictive models can be used to identify patients at high risk for readmission. However, the majority of the existing models are based on data available at discharge. We sought to develop a model to predict hospital readmission using data available soon after admission for isolated CABG surgery. METHODS: Fifty risk factors were included in a bivariate analysis, 16 of which were significantly associated (P < 0.05) with readmissions and were entered into a multivariate logistic regression and removed stepwise, using backward elimination procedures. The derived model was then validated on 896 prospective isolated CABG cases. RESULTS: Of 2589 isolated CABG patients identified between December 1, 2010, and June 30, 2014, 237(9.15%) were readmitted within 30 days. Five risk factors were predictive of 30-day all-cause readmission: age (odds ratio [OR] = 1.03; 95% confidence interval [CI]: 1.01-1.05; P = 0.004), prior heart failure (OR = 1.55; 95%CI: 1.07-2.24; P = 0.020), total albumin prior to surgery (OR = 0.68; 95%CI: 0.05-0.94; P = 0.021), previous myocardial infarction (OR = 1.44; 95%CI: 1.00-2.08; P = 0.50), and history of diabetes (OR = 1.54; 95%CI: 1.09-2.19; P = 0.015). The area under the curve c-statistic was 0.63 in the derivation sample and 0.65 in the validation sample showing good discrimination. CONCLUSIONS: A 30-day all-cause readmission among isolated CABG patients can be predicted soon after admission with a small number of risk factors.
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Puente de Arteria Coronaria , Admisión del Paciente , Readmisión del Paciente/estadística & datos numéricos , Factores de Riesgo , Anciano , Albúminas , Intervalos de Confianza , Diabetes Mellitus , Femenino , Predicción , Insuficiencia Cardíaca , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Análisis Multivariante , Infarto del Miocardio , Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Heart transplantation (HTx) is the preferred treatment for patients with end-stage heart failure and has been successful for >30 y. The clinical course of recipients at the extreme of age is unknown. We reviewed our experience to determine the overall health and prevalence of Tx-related medical problems for recipients in their ninth decade. METHODS: We reviewed the UCTP experience from 1985 to present to identify patients who survived into their 80s and matched (1:1) with other recipients for gender and age at HTx, but did not survive to ≥80 y. The end point was the prevalence of medical problems. RESULTS: Since 1985, 1129 adult HTx have been performed and 14 patients (1.2%) survived to ≥80 y old. The mean age at HTx was 63 ± 4 y. Of octogenarians, the majority were males with ischemic cardiomyopathy. The average survival after transplant was 19 ± 5 y in the octogenarians and 5 ± 5 y in the controls (P < 0.01). Over time, the prevalence of comorbidities increased. Compared with nonoctogenarians, we observed higher prevalence of dyslipidemia (P = 0.02), and chronic renal insufficiency (P = 0.02) during follow-up. Cardiac function was normal (ejection fraction > 55%) for all octogenarians at age 80 y. CONCLUSIONS: Despite improvements in posttransplant care, survival of HTx patients into the ninth decade is rare (1%). For those surviving into their 80s, cardiac function is preserved but dyslipidemia, renal insufficiency, and skin cancers are common. As the age of Htx patients continues to increase, posttransplant care should be tailored to minimize post-HTx complications and further extend survival.
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Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Estado de Salud , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Prevalencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Ventricular assist devices (VADs) have a proven survival benefit in select patients with advanced heart failure, yet many patients considered for implantation are declined for various reasons. The outcome of these patients is obscure owing to their exclusion from recent VAD studies. We aim to compare the outcomes of patients who received a VAD to those who did not. METHODS: For this study, the Artificial Heart Program's database at Intermountain Medical Center was queried from 2006 to 2012 for patients referred for a VAD. Kaplan-Meier survival analysis was performed with log-rank test determining significance. RESULTS: Of 232 patients included, 118 patients received a VAD and 114 patients did not. The prevailing reason for VAD decline in eligible and willing patients was due to pre-existing illness (39%). Mortality was higher in non-VAD vs. VAD patients (58.8% vs. 35.6%, p < 0.001) with a median time-to-death of 67 (IQR:12-314) and 301 (IQR:136-694) d, respectively (p = 0.007). CONCLUSIONS: In the current era of non-pulsatile VADs, mortality of patients who are considered but not implanted remains high. Additionally, mortality of these patients occurred much sooner. Educational efforts ensuring timely referral for VAD therapy are important to maximize the number of patients who may benefit.
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Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Marcapaso Artificial/efectos adversos , Calidad de Vida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Importance: The existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support might be limited, partly due to lack of external validation, marginal predictive power, and absence of intraoperative characteristics. Objective: To derive and validate a risk model to predict RVF after LVAD implantation. Design, Setting, and Participants: This was a hybrid prospective-retrospective multicenter cohort study conducted from April 2008 to July 2019 of patients with advanced heart failure (HF) requiring continuous-flow LVAD. The derivation cohort included patients enrolled at 5 institutions. The external validation cohort included patients enrolled at a sixth institution within the same period. Study data were analyzed October 2022 to August 2023. Exposures: Study participants underwent chronic continuous-flow LVAD support. Main Outcome and Measures: The primary outcome was RVF incidence, defined as the need for RV assist device or intravenous inotropes for greater than 14 days. Bootstrap imputation and adaptive least absolute shrinkage and selection operator variable selection techniques were used to derive a predictive model. An RVF risk calculator (STOP-RVF) was then developed and subsequently externally validated, which can provide personalized quantification of the risk for LVAD candidates. Its predictive accuracy was compared with previously published RVF scores. Results: The derivation cohort included 798 patients (mean [SE] age, 56.1 [13.2] years; 668 male [83.7%]). The external validation cohort included 327 patients. RVF developed in 193 of 798 patients (24.2%) in the derivation cohort and 107 of 327 patients (32.7%) in the validation cohort. Preimplant variables associated with postoperative RVF included nonischemic cardiomyopathy, intra-aortic balloon pump, microaxial percutaneous left ventricular assist device/venoarterial extracorporeal membrane oxygenation, LVAD configuration, Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 to 2, right atrial/pulmonary capillary wedge pressure ratio, use of angiotensin-converting enzyme inhibitors, platelet count, and serum sodium, albumin, and creatinine levels. Inclusion of intraoperative characteristics did not improve model performance. The calculator achieved a C statistic of 0.75 (95% CI, 0.71-0.79) in the derivation cohort and 0.73 (95% CI, 0.67-0.80) in the validation cohort. Cumulative survival was higher in patients composing the low-risk group (estimated <20% RVF risk) compared with those in the higher-risk groups. The STOP-RVF risk calculator exhibited a significantly better performance than commonly used risk scores proposed by Kormos et al (C statistic, 0.58; 95% CI, 0.53-0.63) and Drakos et al (C statistic, 0.62; 95% CI, 0.57-0.67). Conclusions and Relevance: Implementing routine clinical data, this multicenter cohort study derived and validated the STOP-RVF calculator as a personalized risk assessment tool for the prediction of RVF and RVF-associated all-cause mortality.
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Sistema Cardiovascular , Insuficiencia Cardíaca , Corazón Auxiliar , Humanos , Masculino , Persona de Mediana Edad , Estudios de Cohortes , Corazón Auxiliar/efectos adversos , Estudios Prospectivos , Factores de Riesgo , Femenino , Adulto , AncianoRESUMEN
Objective: In chronic heart failure (HF) patients supported with continuous-flow left ventricular assist device (CF-LVAD), we aimed to assess the clinical association of pre-LVAD QRS duration (QRSd) with post-LVAD cardiac recovery, and its correlation with pre- to post-LVAD change in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD). Methods: Chronic HF patients (n = 402) undergoing CF-LVAD implantation were prospectively enrolled, at one of the centers comprising the U.T.A.H. (Utah Transplant Affiliated Hospitals) consortium. After excluding patients with acute HF etiologies, hypertrophic or infiltrative cardiomyopathy, and/or inadequate post-LVAD follow up (<3 months), 315 patients were included in the study. Cardiac recovery was defined as LVEF ≥ 40 % and LVEDD < 6 cm within 12 months post-LVAD implantation. Patients fulfilling this condition were termed as responders (R) and results were compared with non-responders (NR). Results: Thirty-five patients (11 %) achieved 'R' criteria, and exhibited a 15 % shorter QRSd compared to 'NR' (123 ± 37 ms vs 145 ± 36 ms; p < 0.001). A univariate analysis identified association of baseline QRSd with post-LVAD cardiac recovery (OR: 0.986, 95 % CI: 0.976-0.996, p < 0.001). In a multivariate logistic regression model, after adjusting for duration of HF (OR: 0.990, 95 % CI: 0.983-0.997, p = 0.006) and gender (OR: 0.388, 95 % CI: 0.160-0.943, p = 0.037), pre-LVAD QRSd exhibited a significant association with post-LVAD cardiac structural and functional improvement (OR: 0.987, 95 % CI: 0.977-0.998, p = 0.027) and the predictive model showed a c-statistic of 0.73 with p < 0.001. The correlations for baseline QRSd with pre- to post-LVAD change in LVEF and LVEDD were also investigated in 'R' and 'NR' groups. Conclusion: Chronic advanced HF patients with a shorter baseline QRSd exhibit an increased potential for cardiac recovery after LVAD support.
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BACKGROUND: Extrinsic control of cardiomyocyte metabolism is poorly understood in heart failure (HF). FGF21 (Fibroblast growth factor 21), a hormonal regulator of metabolism produced mainly in the liver and adipose tissue, is a prime candidate for such signaling. METHODS: To investigate this further, we examined blood and tissue obtained from human subjects with end-stage HF with reduced ejection fraction at the time of left ventricular assist device implantation and correlated serum FGF21 levels with cardiac gene expression, immunohistochemistry, and clinical parameters. RESULTS: Circulating FGF21 levels were substantially elevated in HF with reduced ejection fraction, compared with healthy subjects (HF with reduced ejection fraction: 834.4 [95% CI, 628.4-1040.3] pg/mL, n=40; controls: 146.0 [86.3-205.7] pg/mL, n=20, P=1.9×10-5). There was clear FGF21 staining in diseased cardiomyocytes, and circulating FGF21 levels negatively correlated with the expression of cardiac genes involved in ketone metabolism, consistent with cardiac FGF21 signaling. FGF21 gene expression was very low in failing and nonfailing hearts, suggesting extracardiac production of the circulating hormone. Circulating FGF21 levels were correlated with BNP (B-type natriuretic peptide) and total bilirubin, markers of chronic cardiac and hepatic congestion. CONCLUSIONS: Circulating FGF21 levels are elevated in HF with reduced ejection fraction and appear to bind to the heart. The liver is likely the main extracardiac source. This supports a model of hepatic FGF21 communication to diseased cardiomyocytes, defining a potential cardiohepatic signaling circuit in human HF.
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Factores de Crecimiento de Fibroblastos , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Insuficiencia Cardíaca/genética , Humanos , Péptido Natriurético Encefálico/genéticaRESUMEN
BACKGROUND: The HeartMate II (HMII) left ventricular assist device (LVAD) has proven reliable and durable and has become the preferred choice for bridge to transplant therapy (BTT) when compared with the pulsatile HeartMate XVE (XVE). In this study, we compared the post-transplant (PTx) outcomes between XVE and HMII using a large national data registry. METHODS: The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) Thoracic Registry database was queried for all patients implanted with either an XVE or an HMII as BTT during 2004-2009. Statistical analysis between XVE and HMII were performed using Kaplan-Meier survival analysis and Cox regression analyses. RESULTS: A total of 673 patients were implanted with the XVE and 484 with HMII. When adjusted for age, gender, ethnicity, intra-aortic balloon pump, ventilator, inotropes, dialysis, body mass index, creatinine, bilirubin, transfusion, pulmonary capillary wedge, and pulmonary arterial pressures, the HMII had similar one- and three-yr survival (hazard ratio = 0.95, CI = 0.64, 1.42) and rejection-free survival PTx compared to XVE. The XVE group had more early incidences of allograft rejection (AR) and hospitalization for infection (HI). CONCLUSIONS: Compared to XVE, patients with HMII have similar one- and three-yr survival after heart transplantation with less risk of early graft rejection and significant infection. With a strong shift toward use of continuous-flow LVADs, PTx outcomes are expected to continue to improve.
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Rechazo de Injerto , Insuficiencia Cardíaca/fisiopatología , Trasplante de Corazón/mortalidad , Ventrículos Cardíacos/fisiopatología , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/cirugía , Ventrículos Cardíacos/cirugía , Corazón Auxiliar , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
It is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.
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The experiment was conducted to examine opportunities for enhancing pork quality through the use of post-mortem ageing when combined with different chilling regimes. Large White (LW, n=24) and Duroc×Large White (Duroc, n=24) barrows were slaughtered and alternate carcass sides were either conventionally or blast-chilled. The longissimus thoracis et lumborum muscle was dissected from the carcass sides (24h post-mortem) and trimmed of cover fat. Three sections (15cm length) were vacuum packaged and assigned to 2, 7 or 14days of ageing (2°C) randomized within muscle location. Blast-chilled meat had lower purge (P=0.009) and drip (P=0.0009) losses and higher hue (P=0.02) than conventionally chilled meat. However chilling by conventional or blast-chilling methods had no effect on sensory characteristics (P>0.1). When breeds were compared, meat from Duroc barrows had lower moisture (P<0.0001) and higher intramuscular fat content (P<0.0001), L∗ (P=0.0003) and hue (P=0.007) values than LW. Overall tenderness (P=0.005), juiciness (P=0.0007) and palatability (P<0.0001), as well as flavour intensity (P<0.0001) and desirability (P<0.0001) values were higher and undesirable flavours were lower (P<0.0001) for meat from Duroc pigs, when compared with LW. Ageing increased purge loss (P<0.0001), L∗ (P<0.0001), hue (P<0.0001), chroma (P<0.0001) and content of protein (P=0.002), with corresponding decreases (P<0.0001) in drip loss and moisture content. Instrumental (P<0.0001) and sensory (initial, P<0.0001 and overall, P<0.0001) tenderness increased from day 2 to 14. Therefore independent of chilling method, ageing improved quality of pork loins. Moreover ageing had greater effect on tenderness, while breed had greater effect on flavour which may be related to differences in intramuscular fat content.
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OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) for stentless bioprosthetic aortic valves (SBAVs) and to identify predictors of adverse events. BACKGROUND: ViV TAVR in SBAVs is associated with unique technical challenges and risks. METHODS: Clinical records and computer tomographic scans were retrospectively reviewed for procedural complications, predictors of coronary obstruction, mortality, and echocardiographic results. RESULTS: Among 66 SBAV patients undergoing ViV TAVR, mortality was 2 of 66 patients (3.0%) at 30 days and 5 of 52 patients (9.6%) at 1 year. At 1 year, left ventricular end-systolic dimension was decreased versus baseline (median [interquartile range (IQR)]: 3.0 [2.6 to 3.6] cm vs. 3.7 [3.2 to 4.4] cm; p < 0.001). Coronary occlusion in 6 of 66 procedures (9.1%) resulted in myocardial infarction in 2 of 66 procedures (3.0%). Predictors of coronary occlusion included subcoronary implant technique compared with full root replacement (6 of 31, 19.4% vs. 0 of 28, 0%; p = 0.01), short simulated radial valve-to-coronary distance (median [IQR]: 3.4 [0.0 to 4.6] mm vs. 4.6 [3.2 to 6.2] mm; p = 0.016), and low coronary height (7.8 [5.8 to 10.0] mm vs. 11.6 [8.7 to 13.9] mm; p = 0.003). Coronary arteries originated <10 mm above the valve leaflets in 34 of 97 unobstructed coronary arteries (35.1%). CONCLUSIONS: TAVR in SBAVs is frequently associated with high-risk coronary anatomy but can be performed with a low risk of death and myocardial infarction, resulting in favorable ventricular remodeling. A subcoronary surgical approach is associated with an increased risk of coronary obstruction.
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Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Prótesis Valvulares Cardíacas , Falla de Prótesis , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/mortalidad , Insuficiencia de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/fisiopatología , Oclusión Coronaria/etiología , Bases de Datos Factuales , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Diseño de Prótesis , Recuperación de la Función , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: The number of centers with left ventricular assist device (LVAD) research programs focused on cardiac recovery is very small. Therefore, this phenomenon has been reported in real-world multi-center registries as a rare event. OBJECTIVES: This study evaluated the incidence of cardiac recovery with an a priori LVAD implantation strategy of bridge-to-recovery (BTR) and constructed a recovery predictive model. METHODS: The study included LVAD recipients registered in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Cardiac recovery was evaluated in BTR and non-BTR patients. A weighted score was derived and externally validated in patients of the Utah Cardiac Recovery (UCAR) program. RESULTS: Of 15,138 INTERMACS patients, cardiac recovery occurred in 192 (1.3%). The incidence of recovery was 11.2% (n = 14) in BTR compared with 1.2% (n = 178) in non-BTR patients (p < 0.0001). Independent predictors of recovery included: age <50 years, non-ischemic cardiomyopathy, time from cardiac diagnosis <2 years, absence of ICD, creatinine ≤1.2 mg/dl, and LVEDD <6.5 cm (c-index: 0.85; p < 0.0001). A weighted score termed I-CARS, effectively stratified patients based on their probability of recovery. I-CARS was validated in the UCAR cohort (n = 190) with good performance (AUC: 0.94; 95% CI: 0.91 to 0.98). One-year survival after LVAD explantation, available in INTERMACS for 21 (11%) patients, was 86%. CONCLUSIONS: The incidence of cardiac recovery is higher in patients implanted with an a priori BTR strategy. We developed a simple tool to help identify patients in whom recovery is feasible. In BTR patients with favorable characteristics, I-CARS suggests a 24% probability of successful LVAD explantation. Large-scale studies to better address post-explantation outcomes are warranted.
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Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Little is known about mixed cellular and antibody-mediated rejection (MR) in heart transplantation. It remains unclear whether cardiac MR has distinctive pathologic and clinical features beyond those of simultaneous cellular rejection (CR) and antibody-mediated rejection (AMR). In this study we systematically explore the pathologic and clinical characteristics of MR in heart transplantation. METHODS: The UTAH Cardiac Transplant Program database was queried for transplant recipients who survived long enough to have at least one endomyocardial biopsy (EMB) between 1985 and 2014. Only EMBs with both CR and AMR scores documented were included. In addition to detailed pathologic analyses, we also examined the incidence and prevalence of MR, the likelihood to transition from and to MR, and mortality associated with MR. RESULTS: Patients (n = 1,207) with a total of 28,484 EMBs met the study inclusion criteria. The overall prevalence of MR was 7.8% and it was nearly twice as frequent within the first year post-transplant. Mild MR was by far the most common occurrence and was typically preceded by an immune active state. When CR increased in severity, AMR tended to follow, but the reverse was not true. On pathology, individual features of CR and AMR were more easily separated in cases of mild MR, whereas they substantially overlapped in more severe cases. MR was associated with a significant cardiovascular death risk that was incremental with severity. CONCLUSIONS: MR is not common, usually occurs early after transplant, and is associated with worse outcomes. MR reflects a complex interplay between cellular and humoral processes, which varies with rejection severity.
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Anticuerpos/inmunología , Rechazo de Injerto/inmunología , Trasplante de Corazón , Inmunología del Trasplante , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/patología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Driveline exit site (DLES) infection is a major complication of ventricular assist devices (VADs). Differences in the sheath material interfacing with exit site tissue appear to affect healing time and infection risk more than site hygiene, but the mechanistic basis for this is not clear. METHODS: Health record data from Utah Artificial Heart Program patients with HeartMate II (HMII) devices implanted from 2008 to 2012 were retrospectively reviewed, with particular attention to interface type, incorporation (healing) time, and infections. Tissue samples from the DLES were collected at the time of VAD removal in a small subset. These samples were examined by routine histology and environmental scanning electron microscopy (ESEM). RESULTS: Among 57 patients with sufficient data, 15 had velour interfaces and 42 had silicone. Indications for and duration of support were similar between the groups. The silicone group had shorter incorporation time (45 ±22 vs. 56 ±34 days, P=.17) and fewer DLES infections (20% vs. 1.7%, P=.026, for patient infections and 0.0340 vs. 0.166, P=.16, for infections per patient-year). Tissues from five patients, three with velour, were examined. Velour interfaces demonstrated more hyperkeratosis, hypergranulosis, and dermal inflammation. By ESEM, the silicone driveline tracts appeared relatively smooth and flat, whereas the velour interface samples were irregular with deep fissures and globular material adhering to the surface. CONCLUSIONS: Using the silicone portion of the HMII driveline at the DLES was associated with fewer infections and a trend toward faster healing in this small retrospective series. Whether the intriguing microscopic differences directly account for this needs further study on a larger scale.
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Corazón Auxiliar/efectos adversos , Poliésteres/efectos adversos , Infecciones Relacionadas con Prótesis/etiología , Siliconas/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/epidemiologíaRESUMEN
Camelina sativa is an oil seed crop which can be grown on marginal lands. Camelina seed oil is rich in omega-3 fatty acids (>35%) and γ-tocopherol but is also high in erucic acid and glucosinolates. Camelina meal, is the by-product after the oil has been extracted. Camelina meal was fed to 28 d old weaned pigs at 3.7% and 7.4% until age 56 d. The camelina meal supplements in the soy based diets, improved feed efficiency but also significantly increased the liver weights. Gene expression analyses of the livers, using intra-species microarrays, identified increased expression of phase 1 and phase 2 drug metabolism enzymes. The porcine versions of the enzymes were confirmed by real time PCR. Cytochrome 8b1 (CYP8B1), aldehyde dehydrogenase 2 (Aldh2), and thiosulfate transferase (TST) were all significantly stimulated. Collectively, these genes implicate the camelina glucosinolate metabolite, methyl-sulfinyldecyl isothiocyanate, as the main xeniobiotic, causing increased hepatic metabolism and increased liver weight.
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The transseptal approach is a useful technique for patients who have valvular disease involving both the mitral and tricuspid valves. This incision provides excellent exposure for addressing pathology on both valves and has the added advantage of extension up onto the dome of the left atrium if additional exposure required. This exposure provides the ability to perform the full range of reparative operations or valve replacement with minimal distortion of the heart.
RESUMEN
Presumably, dry-ageing enhances flavour attributes of meat by surface desiccation to increase and modify fatty acid content and other organoleptic molecules. However information regarding dry-ageing of fresh pork is limited. To examine the effects of dry-ageing on pork quality, Large White (LW, n = 24) and Large White × Duroc (Duroc, n = 24) barrows were slaughtered and three longissimus thoracis et lumborum sections from each side of the carcass were wet or dry-aged for 2, 7 or 14 d. Dry-aged meat had lower (P < 0.001) moisture and higher (P < 0.001) protein content due to higher purge losses (P < 0.001) when compared with wet aged meat. However no dry-ageing effect (P > 0.05) was observed on sensory characteristics. The increase in the duration of ageing decreased moisture content and drip loss and increased (P < 0.001) protein content, purge loss and L*, chroma and hue values. These changes were more accentuated in dry-aged meat (P < 0.01). Days of ageing dependent increases (P < 0.001) were observed for instrumental and sensory tenderness and juiciness in both ageing types. Moreover, meat from Duroc barrows had lower (P < 0.001) moisture and protein content, and higher (P < 0.01) fat content, L* and hue values. Instrumental and sensory tenderness, juiciness and flavour were higher (P < 0.01) in meat from Duroc than LW barrows. Increases (P < 0.01) in flavour intensity and decreases in off-flavour of meat from LW barrows were greater (P < 0.05) in d 7 than in d 14. Therefore the duration of ageing affected most quality and sensory characteristics, while the changes to quality attributes of dry versus wet-aged pork were attributable to the differences in shrink losses in the present study.
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Tejido Adiposo/metabolismo , Manipulación de Alimentos/métodos , Productos de la Carne/análisis , Músculo Esquelético/metabolismo , Mataderos , Tejido Adiposo/crecimiento & desarrollo , Animales , Genotipo , Músculo Esquelético/crecimiento & desarrollo , Porcinos/genética , Factores de TiempoRESUMEN
BACKGROUND: The use of left ventricular assist devices (LVADs) as destination therapy (DT) is increasing and has proven beneficial in prolonging survival and improving quality of life in select patients with end-stage heart failure. Nonetheless, end-of-life (EOL) issues are inevitable and how to approach them underreported. METHODS: Our DT data registry was queried for eligible patients, defined as those individuals who actively participated in EOL decision making. The process from early EOL discussion to palliation and death was reviewed. We recorded the causes leading to EOL discussion, time from EOL decision to withdrawal and from withdrawal to death, and location. Primary caregivers were surveyed to qualify their experience and identify themes relevant to this process. RESULTS: Between 1999 and 2009, 92 DT LVADs were implanted in 69 patients. Twenty patients qualified for inclusion (mean length of support: 833 days). A decrease in quality of life from new/worsening comorbidities usually prompted EOL discussion. Eleven patients died at home, 8 in the hospital and 1 in a nursing home. Time from EOL decision to LVAD withdrawal ranged from <1 day to 2 weeks and from withdrawal until death was <20 minutes in all cases. Palliative care was provided to all patients. Ongoing assistance from the healthcare team facilitated closure and ensured comfort at EOL. CONCLUSIONS: With expanding indications and improved technology, more DT LVADs will be implanted and for longer durations, and more patients will face EOL issues. A multidisciplinary team approach with protocols involving DT patients and their families in EOL decision making allows for continuity of care and ensures dignity and comfort at EOL.
Asunto(s)
Cuidadores/psicología , Toma de Decisiones , Insuficiencia Cardíaca , Corazón Auxiliar , Cuidado Terminal , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Humanos , Masculino , Persona de Mediana Edad , Relaciones Profesional-Familia , Investigación Cualitativa , Calidad de Vida , Factores de Tiempo , Adulto JovenRESUMEN
The (15)N-isotope dilution technique ((15)N-IDT), with either pulse-dose oral administration or continuous i.v. administration of [(15)N]-l-leucine (carotid artery), both at 5 mg/(kg body weight . d), was used to measure ileal (postvalve T-cecum cannula) endogenous nitrogen recovery (ENR) in pigs (9 +/- 0.6 kg). Diets were cornstarch, enzyme-hydrolyzed casein with no (control) or high (4%) content of quebracho extract (Schinopsis spp.) rich in condensed tannins. Blood was sampled from a catheter in the external jugular vein. Mean plasma (15)N-enrichment at d 8-10 was higher (P = 0.0009) after i.v. than after oral administration [0.0356 vs. 0.0379 atom% excess (APE)]. Plasma (15)N-enrichment for i.v. infused pigs was 0.01117 APE higher (P < 0.0001) and for orally dosed pigs 0.0081 APE lower (P < 0.0001) at 11 h postprandial compared with 1 h postprandial. Apparent ileal N digestibility was higher (P < 0.0001) for the control (85.5%) than for the quebracho diet (69.5%). ENR was calculated from the ratio of (15)N-enrichment of plasma and digesta. The ENR for the quebracho diet was approximately 300% higher than for the control diet (6.03 vs. 1.94 g/kg dry matter intake, P < 0.001). The real N digestibility (92.2 +/- 0.4%) was equal for both diets (P = 0.1030) and both tracer methods (P = 0.9730). We concluded that oral administration of [(15)N]leucine provides reasonable estimates of ENR in pigs fed semipurified diets with high or low content of tannins; however, one must be careful in extrapolating this conclusion to studies with other protein sources or feeding frequencies.