RESUMEN

BACKGROUND: There are no criteria guiding the timing of heart transplant referral for Fontan patients, nor are there any characteristics of those deferred or declined listing reported. This study examines comprehensive transplant evaluations for Fontan patients of all ages, listing decisions, and outcomes to inform referral practices. METHODS: Retrospective review of 63 Fontan patients formally assessed by the advanced heart failure service and presented at Mayo Clinic transplant selection committee meetings (TSM) January 2006 to April 2021. The study is compliant with the Helsinki Congress and Declaration of Istanbul and included no prisoners. Statistical analysis was performed with Wilcoxon Rank Sum and Fisher's Exact tests. RESULTS: Median age at TSM was 26 years (17.5, 36.5). Most were approved (38/63 [60%]); 9 of 63 (14%) were deferred and 16 of 63 (25%) were declined. Approved patients more commonly were <18 years old at TSM (15/38 [40%] vs 1/25 [4%], P = .002) compared with those deferred/declined. Complications of Fontan circulatory failure were less common in approved vs deferred/declined patients: ascites (15/38 [40%] vs 17/25 [68%], P = .039), cirrhosis (16/38 [42%] vs 19/25 [76%], P = .01), and renal insufficiency (6/38 [16%] vs 11/25 [44%], P = .02). Ejection fraction and atrioventricular valve regurgitation did not differ between groups. Pulmonary artery wedge pressure was overall high normal (12 mm Hg [9,16]) but higher in deferred/declined vs approved patients, 14.5 (11, 19) vs 10 (8, 13.5) mm Hg, P = .015. Overall survival was significantly lower in deferred/declined patients (P = .0018). CONCLUSION: Fontan patient referral for heart transplant at younger age and before the onset of end-organ complications is associated with increased approval for transplant listing.

Asunto(s)

Procedimiento de Fontan , Cardiopatías Congénitas , Trasplante de Corazón , Humanos , Adulto , Adolescente , Cardiopatías Congénitas/cirugía , Procedimiento de Fontan/efectos adversos , Trasplante de Corazón/efectos adversos , Cirrosis Hepática/complicaciones , Estudios Retrospectivos

RESUMEN

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

Asunto(s)

Sangre Fetal , Cardiopatías Congénitas , Animales , Adaptación Fisiológica , Proliferación Celular , Tratamiento Basado en Trasplante de Células y Tejidos , Método Doble Ciego , Cardiopatías Congénitas/patología , Ventrículos Cardíacos , Miocitos Cardíacos/patología , Porcinos

RESUMEN

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein-Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8-26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04-0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03-0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.

RESUMEN

BACKGROUND: Enhanced platelet reactivity may play a role in cardiac allograft vasculopathy (CAV) progression. The use of antiplatelet agents after heart transplantation (HT) has been inconsistent and although aspirin (ASA) is often a part of the medication regimen after HT, limited evidence is available on its benefit. METHODS AND RESULTS: CAV progression was assessed by measuring the difference in plaque volume and plaque index between the last follow-up and the baseline coronary intravascular ultrasound examination. Overall, 529 HT recipients were retrospectively analyzed (337 had ≥2 intravascular ultrasound studies). The progression in plaque volume (P = .007) and plaque index (P = .002) was significantly attenuated among patients treated with early ASA (within the first year after HT). Over a 6.7-year follow-up, all-cause mortality was lower with early ASA compared with late or no ASA use (P < .001). No cardiac deaths were observed in the early ASA group, and the risk of CAV-related graft dysfunction was significantly lower in this group (P = .03). However, the composite of all CAV-related events (cardiac death, CAV-related graft dysfunction, or coronary angioplasty) was not significantly different between the groups (P = .16). CONCLUSIONS: Early ASA use after HT may delay CAV progression and decrease mortality and CAV-related graft dysfunction, but does not seem to affect overall CAV-associated events.

Asunto(s)

Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Trasplante de Corazón , Aloinjertos , Aspirina/uso terapéutico , Angiografía Coronaria , Trasplante de Corazón/efectos adversos , Humanos , Estudios Retrospectivos

RESUMEN

BACKGROUND: In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation. OBJECTIVES: The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection. METHODS: Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained. RESULTS: A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction. CONCLUSIONS: A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.

Asunto(s)

Rechazo de Injerto/prevención & control , Trasplante de Corazón , Trasplante de Hígado , Inmunología del Trasplante , Adulto , Protocolos Clínicos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.

Asunto(s)

Trasplante de Corazón , Inmunosupresores , Aloinjertos , Trasplante de Corazón/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Proteinuria , Serina-Treonina Quinasas TOR

RESUMEN

Ribonucleoprotein (RNP) granules are biomolecular condensates-liquid-liquid phase-separated droplets that organize and manage messenger RNA metabolism, cell signaling, biopolymer assembly, biochemical reactions and stress granule responses to cellular adversity. Dysregulated RNP granules drive neuromuscular degenerative disease but have not previously been linked to heart failure. By exploring the molecular basis of congenital dilated cardiomyopathy (DCM) in genome-edited pigs homozygous for an RBM20 allele encoding the pathogenic R636S variant of human RNA-binding motif protein-20 (RBM20), we discovered that RNP granules accumulated abnormally in the sarcoplasm, and we confirmed this finding in myocardium and reprogrammed cardiomyocytes from patients with DCM carrying the R636S allele. Dysregulated sarcoplasmic RBM20 RNP granules displayed liquid-like material properties, docked at precisely spaced intervals along cytoskeletal elements, promoted phase partitioning of cardiac biomolecules and fused with stress granules. Our results link dysregulated RNP granules to myocardial cellular pathobiology and heart failure in gene-edited pigs and patients with DCM caused by RBM20 mutation.

Asunto(s)

Cardiomiopatía Dilatada/genética , Miocardio/metabolismo , Proteínas de Unión al ARN/genética , Ribonucleoproteínas/genética , Alelos , Animales , Cardiomiopatía Dilatada/fisiopatología , Reprogramación Celular , Modelos Animales de Enfermedad , Femenino , Edición Génica , Humanos , Masculino , Mutación/genética , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , ARN Mensajero/genética , Retículo Sarcoplasmático/genética , Retículo Sarcoplasmático/metabolismo , Vesículas Secretoras/genética , Vesículas Secretoras/metabolismo , Porcinos

RESUMEN

Background The presence of a durable left ventricular assist device (LVAD) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation (HT). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD. Methods and Results We identified 94 patients who underwent HT after bridging with continuous-flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT. Patients with and without vasoplegia had similar preoperative LVAD, echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P=0.010), longer LVAD support (odds ratio: 1.06 per month; P=0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P=0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P=0.044) were independent predictors of vasoplegia. After mean follow-up of 4.0 years after HT, vasoplegia was associated with increased risk of all-cause mortality (hazard ratio: 5.20; 95% CI, 1.71-19.28; P=0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.

Asunto(s)

Insuficiencia Cardíaca/terapia , Trasplante de Corazón , Corazón Auxiliar , Complicaciones Posoperatorias/epidemiología , Vasoplejía/epidemiología , Adulto , Factores de Edad , Anciano , Cardiomiopatía Dilatada/complicaciones , Puente Cardiopulmonar/estadística & datos numéricos , Causas de Muerte , Comorbilidad , Creatinina/sangre , Femenino , Cardiopatías Congénitas/complicaciones , Insuficiencia Cardíaca/etiología , Humanos , Trasplante de Riñón/estadística & datos numéricos , Trasplante de Hígado/estadística & datos numéricos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mortalidad , Análisis Multivariante , Isquemia Miocárdica/complicaciones , Tempo Operativo , Modelos de Riesgos Proporcionales , Factores de Riesgo , Tasa de Supervivencia , Enfermedades de la Tiroides/epidemiología , Factores de Tiempo

RESUMEN

Background Diastolic pulmonary gradient (DPG) was proposed as a better marker of pulmonary vascular remodeling compared with pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG). The prognostic significance of DPG in patients requiring a left ventricular assist device (LVAD) remains unclear. We sought to investigate whether pre-LVAD DPG is a predictor of survival or right ventricular (RV) failure post-LVAD. Methods and Results We retrospectively reviewed 268 patients who underwent right heart catheterization before LVAD implantation from 2007 to 2017 and had pulmonary hypertension because of left heart disease. Patients were dichotomized using DPG ≥7 mm Hg, PVR ≥3 mm Hg, or TPG ≥12 mm Hg. The associations between these parameters and all-cause mortality or RV failure post LVAD were assessed with Cox proportional hazards regression and Kaplan-Meier analyses. After a mean follow-up time of 35 months, elevated DPG was associated with increased risk of RV failure (hazard ratio [HR]: 3.30; P=0.004, for DPG ≥7 versus DPG <7), whereas elevated PVR (HR 1.85, P=0.13 for PVR ≥3 versus PVR <3) or TPG (HR 1.47, P=0.35, for TPG ≥12 versus TPG <12) were not associated with the development of RV failure. Elevated DPG was not associated with mortality risk (HR 1.16, P=0.54, for DPG ≥7 versus DPG <7), whereas elevated PVR, but not TPG, was associated with higher mortality risk (HR 1.55; P=0.026, for PVR ≥3 versus PVR <3). Conclusions Among patients with pulmonary hypertension because of left heart disease requiring LVAD support, elevated DPG was associated with RV failure but not survival, while elevated PVR predicted mortality post LVAD implantation.

Asunto(s)

Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Hipertensión Pulmonar/fisiopatología , Disfunción Ventricular Izquierda/terapia , Disfunción Ventricular Derecha/fisiopatología , Anciano , Cateterismo Cardíaco , Diástole , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Humanos , Hipertensión Pulmonar/etiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Presión , Pronóstico , Modelos de Riesgos Proporcionales , Arteria Pulmonar , Presión Esfenoidal Pulmonar , Estudios Retrospectivos , Medición de Riesgo , Remodelación Vascular/fisiología , Resistencia Vascular/fisiología , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Derecha/epidemiología

RESUMEN

BACKGROUND: Malignancy is a major cause of late post-heart transplantation (HT) mortality. Sirolimus (SRL) exerts antiproliferative properties and its long-term use in HT as primary immunosuppression (IS) is associated with decreased mortality risk that is not fully explained by attenuation of cardiac allograft vasculopathy progression. OBJECTIVES: This study sought to examine whether conversion from calcineurin inhibitor (CNI)-based to SRL-based IS was associated with decreased risk of malignancy post-HT. METHODS: Overall, 523 patients underwent HT between 1994 and 2016 at a single institution. The main outcomes included incidence of overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]), post-transplantation lymphoproliferative disorders (PTLD), and first and subsequent primary occurrences of NMSC post-HT. RESULTS: The study identified 307 patients on SRL-based and 216 on CNI-based maintenance IS. Over a median follow-up of 10 years after HT, overall de novo malignancies (non-NMSC) occurred in 31% of CNI patients and in 13% of SRL patients (adjusted hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.18 to 0.62; p < 0.001). The incidence of the first NMSC was similar in the SRL and CNI groups (HR: 0.92; 95% CI: 0.66 to 1.28; p = 0.62). However, conversion to SRL was significantly associated with a decreased risk of subsequent primary occurrences of NMSC compared with that of CNI (adjusted HR: 0.44; 95% CI: 0.28 to 0.69; p < 0.001). The adjusted PTLD risk was significantly decreased in the SRL group (HR: 0.13; 95% CI: 0.03 to 0.59; p = 0.009). Late survival post-HT was markedly decreased in patients who developed non-NMSC, PTLD, or non-PTLD compared with patients who did not develop these malignancies, whereas NMSC had no significant effect on survival. CONCLUSIONS: Conversion to SRL was associated with a decreased risk of all de novo malignancies, PTLD, and subsequent primary occurrences of NMSC after HT. These findings provided further explanation of the late survival benefit with long-term SRL use.

Asunto(s)

Inhibidores de la Calcineurina/efectos adversos , Trasplante de Corazón/mortalidad , Inmunosupresores/efectos adversos , Neoplasias/epidemiología , Sirolimus/efectos adversos , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Neoplasias/inducido químicamente , Estudios Retrospectivos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiología

RESUMEN

BACKGROUND: Sirolimus (SRL) attenuates cardiac allograft vasculopathy (CAV) progression after heart transplantation (HT) but often results in hyperlipidemia. In this study we investigated the differential effects of SRL-based and calcineurin inhibitor (CNI)-based immunosuppression on CAV progression and clinical outcomes in HT recipients. METHODS: CAV progression was assessed by coronary intravascular ultrasound (IVUS) as changes in volumetric measurements after correction to time between the first and last follow-up IVUS exams. CAV progression rate and CAV-associated events were compared between patients with mean follow-up low-density lipoprotein (LDL) <100 mg/dl (lower level or LL) and ≥100 mg/dl (higher level or HL) in the SRL and CNI groups. RESULTS: We identified 227 patients on SRL (LL: 118; HL: 109) and 96 on CNI (LL: 56; HL: 40), with a median follow-up of 6.7 years. Clinical characteristics did not differ between the LL and HL groups and all patients were on statins. In the SRL arm, there were no significant differences in CAV progression rate and there were no differences in all-cause mortality and CAV-associated events between the LL and HL groups. In the CNI arm, the Δ change in plaque volume normalized to segment length and time of follow-up (PV/SL/year) (0.55 ± 0.53 vs 1.53 ± 2.32, p = 0.003) and Δ change in plaque index per year (defined as PV/vessel volume ratio) (3.1 ± 3.7% vs 6.3 ± 10.4%; p = 0.034) were significantly lower in the LL than the HL group. After adjusting for patient characteristics, HL was associated with higher rates of advanced CAV requiring coronary angioplasty (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.05 to 9.40, p = 0.040) and higher rates of all CAV-associated events (HR 2.2, 95% CI 1.10 to 4.54, p = 0.026) in these CNI-treated subjects. CONCLUSION: Unlike CNI-based immunosuppression, the effects of SRL on attenuating CAV progression are independent of LDL cholesterol levels post-HT.

Asunto(s)

Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Trasplante de Corazón , Hipercolesterolemia/inducido químicamente , Inmunosupresores/efectos adversos , Sirolimus/efectos adversos , Adulto , Inhibidores de la Calcineurina/efectos adversos , Inhibidores de la Calcineurina/uso terapéutico , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Progresión de la Enfermedad , Sustitución de Medicamentos , Femenino , Estudios de Seguimiento , Trasplante de Corazón/mortalidad , Humanos , Hipercolesterolemia/diagnóstico por imagen , Hipercolesterolemia/mortalidad , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sirolimus/uso terapéutico , Tasa de Supervivencia , Ultrasonografía Intervencional

RESUMEN

AIMS: Early studies from the 1990s have shown that statins improve survival and attenuate cardiac allograft vasculopathy (CAV). However, little contemporary data are available on the incremental benefit of statins with the current use of new-generation immunosuppressive agents and the use of coronary intravascular ultrasound for assessment of CAV. We sought to investigate the effect of early statin (ES) as compared with late statin (LS) initiation after heart transplantation (HT) on long-term CAV progression and clinical outcomes in a large contemporary HT cohort. METHODS AND RESULTS: We analysed a cohort of 409 adult HT recipients. CAV progression was assessed by serial coronary intravascular ultrasound volumetric measurements of the differences between baseline and last follow-up plaque volume (PV) and plaque index (PV/vessel volume ratio). CAV progression and clinical outcomes were compared between the ES (<2 years after HT) and the LS (>2 years after HT) groups. During a median follow-up of 8.2 years, ES resulted in significantly lower change (Δ) of plaque index (+3.8% ± 1.7% vs. +8.2% ± 3.6%; P = 0.0008) and PV (+0.8 ± 0.3 vs. +1.9 ± 1.2; P = 0.045) compared with LS group. In a Cox proportional hazards regression model and after adjustment for baseline characteristics, ES was associated with a 52% decreased risk of CAV-associated events (hazard ratio 0.48, 95% confidence interval: 0.27-0.91; P = 0.025) and a 42% decreased risk of the composite endpoint of all-cause mortality and CAV-associated events (hazard ratio 0.58, 95% confidence interval: 0.38-0.91; P = 0.019). CONCLUSIONS: Early initiation of statin therapy after HT results in attenuated CAV progression as well as in decreased CAV-related events and mortality.

Asunto(s)

Acilcoenzima A/antagonistas & inhibidores , Vasos Coronarios/diagnóstico por imagen , Rechazo de Injerto/tratamiento farmacológico , Trasplante de Corazón/efectos adversos , Inmunosupresores/administración & dosificación , Enfermedades Vasculares/tratamiento farmacológico , Aloinjertos , Biopsia , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Tiempo de Tratamiento , Ultrasonografía Intervencional , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etiología

RESUMEN

OBJECTIVE: To investigate differences in invasive hemodynamic parameters and outcomes in patients with and without heart failure (HF) symptoms after left ventricular assist device (LVAD) implantation. PATIENTS AND METHODS: We performed a single-center retrospective analysis of 51 symptomatic patients and 50 patients with resolved HF symptoms who underwent right-sided heart catheterization (RHC) after LVAD implantation from March 1, 2007, through June 30, 2016. Patient characteristics and outcomes including all-cause mortality and right ventricular (RV) failure were compared between groups. RESULTS: Fifty-one patients had development of HF symptoms after LVAD implantation and underwent RHC a mean ± SD of 243.7±288 days postoperatively. Fifty asymptomatic LVAD recipients underwent routine RHC 278.6±205 days after implantation. Compared with patients who had resolved HF symptoms, symptomatic patients were older, more likely to be male, and more likely to have ischemic cardiomyopathy. Symptomatic patients had higher right atrial pressure (P<.001), mean pulmonary arterial pressure (P<.001), and pulmonary capillary wedge pressure (P<.001). Improvements in right atrial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure before and after LVAD implantation were less remarkable in symptomatic patients. The frequency of RV dysfunction was significantly higher among symptomatic patients than patients with resolved HF symptoms (P=.001). Symptomatic patients displayed significantly higher risk of all-cause mortality (hazard ratio, 3.0; 95% CI, 1.3-6.5; P=.007) and RV failure (hazard ratio, 6.2; 95% CI, 1.3-29.7; P=.02) independent of other predictors of outcome. CONCLUSION: Patients with recurrent HF symptoms after LVAD implantation display more profound hemodynamic derangements, greater burden of RV failure, and increased rates of all-cause mortality compared with LVAD recipients with resolved HF symptoms.

Asunto(s)

Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Complicaciones Posoperatorias/epidemiología , Disfunción Ventricular Derecha/epidemiología , Anciano , Presión Sanguínea , Cateterismo Cardíaco , Gasto Cardíaco , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resistencia Vascular

RESUMEN

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation (HT). Uric acid (UA) may play a role in CAV due to its role in stimulating T-cell-mediated immunity. Sirolimus is associated with CAV attenuation through a number of mechanisms, including immune-mediated effects. We aimed to determine whether UA is an independent predictor of CAV and whether conversion to sirolimus as primary immunosuppression modulates UA levels. METHODS: We retrospectively analyzed a cohort of 224 patients who underwent HT between 2004 and 2015 and had serial coronary intravascular ultrasound (IVUS) studies. Serum UA levels were measured at baseline and last follow-up IVUS in all participants. CAV progression was assessed by measuring the change in plaque volume (ΔPV) and plaque index (ratio of plaque volume to vessel volume [ΔPI]) between last follow-up and baseline IVUS after correction for time of follow-up. RESULTS: Patients with high (≥7 mg/dl) compared with low (<7 mg/dl) UA had increased median ΔPV (0.33 [interquartile range 0.08 to 0.93] vs 0.07 [-0.17 to 0.38] mm3/mm/year; p < 0.001) and ΔPI (2.0% [0.31% to 3.9%] vs 0.33% [-1.2% to 2.0%]; p < 0.001). Elevated UA levels were associated with a significantly increased risk of developing significant CAV progression (ΔPV >0.50 mm3/mm) (hazard ratio 2.2, 95% confidence interval 1.1 to 4.6; p = 0.037). Sirolimus resulted in decreased UA levels (5.8 ± 1.4 vs 5.2 ± 1.5; p = 0.002) and patients converted to sirolimus and had low UA levels had the least CAV progression (p < 0.001). After adjustment for potential confounders, change in UA level was also an independent predictor of CAV progression. CONCLUSIONS: UA is an independent predictor of CAV after HT. Sirolimus is associated with decreased UA levels and may explain one of the mechanisms by which sirolimus attenuates CAV progression.

Asunto(s)

Enfermedad de la Arteria Coronaria/inmunología , Trasplante de Corazón , Complicaciones Posoperatorias/inmunología , Ácido Úrico/sangre , Adulto , Anciano , Estudios de Cohortes , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Sirolimus/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Ultrasonografía Intervencional

RESUMEN

BACKGROUND: The true prevalence of heart failure due to wild type transthyretin amyloidosis (ATTRwt) is likely underestimated. There is a paucity of data with regard to the management of ATTRwt-related advanced heart failure and the natural history of extracardiac ATTRwt. METHODS: We conducted a retrospective cohort study of patients undergoing cardiac transplant (HTx) for ATTRwt at a single institution. Comprehensive clinical data, including baseline hemodynamic and echocardiographic characteristics, and posttransplant outcomes, were obtained. RESULTS: Seven patients with ATTRwt underwent HTx between 2007 and 2015. All patients were male with a mean age of 66 ± 9. Patients had a reduced ejection fraction (mean, 37 ± 14%) and elevated filling pressures pre-HTx (mean pulmonary capillary wedge pressure 22 ± 7 mm Hg) before HTx. Three-year survival was 100%; 1 patient died of pancreatic cancer 45 months post-HTx (1 death per 30.8 patient-years). Oxygen consumption (Δ +6.8 ± 4.9 mL·kg·min) and 6-minute walk distances (Δ +189 ± 60 m) improved. Symptomatic gastrointestinal involvement (n = 2) and peripheral nerve involvement (n = 4) by ATTRwt developed late. CONCLUSIONS: This is the first report of a series of ATTRwt patients receiving HTx in which excellent outcomes are demonstrated. Although cardiac death is averted, systemic manifestations of ATTRwt may develop posttransplantation.

Asunto(s)

Neuropatías Amiloides Familiares/cirugía , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Anciano , Neuropatías Amiloides Familiares/diagnóstico por imagen , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/fisiopatología , Ecocardiografía , Tolerancia al Ejercicio , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Trasplante de Corazón/efectos adversos , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Minnesota , Recuperación de la Función , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular Izquierda , Función Ventricular Derecha , Prueba de Paso

RESUMEN

BACKGROUND: Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking. OBJECTIVES: The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. METHODS: A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. RESULTS: The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume-to-vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT. CONCLUSIONS: Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.

Asunto(s)

Rechazo de Injerto/prevención & control , Trasplante de Corazón/tendencias , Inmunosupresores/administración & dosificación , Sirolimus/administración & dosificación , Receptores de Trasplantes , Adulto , Anciano , Inhibidores de la Calcineurina/administración & dosificación , Estudios de Cohortes , Esquema de Medicación , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo

RESUMEN

BACKGROUND: Diabetes mellitus (DM) is a risk factor for morbidity and mortality in patients with heart failure. The effect of DM on post-left ventricular assist device (LVAD) implantation outcomes is unclear. This study sought to investigate whether patients with DM had worse outcomes than patients without DM after LVAD implantation and whether LVAD support resulted in a better control of DM. METHODS AND RESULTS: We retrospectively reviewed 341 consecutive adults who underwent implantation of LVAD from 2007 to 2016. Patient characteristics and adverse events were studied and compared between patients with and without DM. One hundred thirty-one patients (38%) had DM. Compared with patients without DM, those with DM had higher rates of ischemic cardiomyopathy, LVAD implantation as destination therapy, and increased baseline body mass index. In a proportional hazards (Cox) model with adjustment for relevant covariates and median follow-up of 16.1 months, DM was associated with increased risk of all-cause mortality (hazard ratio, 1.73; 95% confidence interval: 1.18-2.53; P=0.005) and increased risk of nonfatal LVAD-related complications, including a composite of stroke, pump thrombosis, and device infection (hazard ratio, 2.1; 95% confidence interval: 1.35-3.18; P=0.001). Preoperative hemoglobin A1c was not significantly associated with mortality or adverse events among patients with DM. LVAD implantation resulted in a remarkable decrease in hemoglobin A1c levels (7.4±1.9 pre-LVAD versus 6.0±1.5 and 6.3±1.4 after 3 and 12 months post-LVAD, respectively; P<0.0001) and a significant reduction in requirements of DM medications. CONCLUSIONS: DM is associated with increased rates of all-cause mortality and major adverse events despite favorable glycemic control after LVAD implantation.

Asunto(s)

Diabetes Mellitus/tratamiento farmacológico , Cardiomiopatías Diabéticas/terapia , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Hipoglucemiantes/uso terapéutico , Función Ventricular Izquierda , Anciano , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Distribución de Chi-Cuadrado , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidad , Cardiomiopatías Diabéticas/diagnóstico , Cardiomiopatías Diabéticas/mortalidad , Cardiomiopatías Diabéticas/fisiopatología , Femenino , Hemoglobina Glucada/metabolismo , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Minnesota , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento

Asunto(s)

Enfermedad de la Arteria Coronaria/inmunología , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Corazón , Isoanticuerpos/inmunología , Monitorización Inmunológica/métodos , Adulto , Aloinjertos , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/diagnóstico , Trasplante de Corazón/efectos adversos , Humanos , Isoanticuerpos/sangre , Masculino , Persona de Mediana Edad , Minnesota , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven

RESUMEN

Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m2 at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function.

Asunto(s)

Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Factores de Edad , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Insuficiencia Cardíaca/complicaciones , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento