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1.
J Gen Intern Med ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358498

RESUMEN

BACKGROUND: U.S. News and World Report 2022-2023 hospital rankings were used to investigate the leadership practices and organizational structure of ranked healthcare institutions. METHODS: Institutional variables including physician leadership status, executive board size, number of physician board members, type of physician practice, health system size, and for-profit status were collected. US News and World Report scores were used to create a comprehensive institutional rank order list. Strength of association was evaluated between these variables and the organization's US News and World Report rank. RESULTS: Our analysis included 546 institutions representing 1676 hospitals. Leadership under a physician CEO (OR 1.59 (95% CI 1.27, 2.00) P < 0.001), group practice (OR 1.25 (95% CI 1.01, 1.59) P = 0.042), and bed count of the institution's highest-ranking hospital (OR 1.001 (95% CI 1.0009, 1.0014) P < 0.001) were associated with higher US News and World Report ranking. For-profit status was negatively associated with institution ranking (OR 0.44 (95% CI 0.24, 0.78) P = 0.005). No significant association was demonstrated between number of physician executive board members, health system bed count, executive board size, or the number of hospitals in a health system and the institutional ranking. CONCLUSIONS: Physician leadership, organizational structure, size of the institution's flagship hospital, and tax status are significantly associated with an organization's US News and World Report rank.

2.
Artif Organs ; 48(10): 1180-1189, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38803277

RESUMEN

BACKGROUND: The Organ Procurement and Transplantation Network (OPTN) implemented modifications in 2018 to the adult heart transplant allocation system to better stratify the most medically urgent transplant candidates. We evaluated the impact of these changes on patients supported by a durable left ventricular assist device (LVAD) with chronic kidney disease (CKD). OBJECTIVE: To evaluate the impact of the OPTN policy change on patients supported by durable left ventricular assist devices (LVAD) with chronic kidney disease (CKD). METHODS: We performed an analysis of patients from the United Network of Organ Sharing Database supported by durable LVAD listed for a heart transplant (HT) between October 17, 2016 and September 30, 2021. Patients were divided into two groups: pre- and postpolicy, depending on whether they were listed on or prior to October 17, 2018. Patients who were on dialysis prior to surgery or discharge were excluded from the analysis. Patients with simultaneous heart and kidney transplants were excluded. Patients who were listed for transplant prepolicy change but transplanted postpolicy change were excluded. This cohort was then subdivided into degrees of CKD based on estimated glomerular filtration rate (eGFR), which resulted in 678 patients (23.7%) in Stage 1 (GFR ≥89.499) (Prepolicy: 345, Postpolicy: 333), 1233 (43.1%) in Stage 2 (89.499 > GFR ≥ 59.499) (Prepolicy: 618, Postpolicy: 615), 613 (21.4%) in Stage 3a (59.499 > GFR ≥ 44.499) (Prepolicy: 291, Postpolicy: 322), 294 (10.3%) in Stage 3b (44.499 > GFR ≥ 29.499) (Prepolicy: 143, Postpolicy: 151), 36 (1.3%) in Stage 4 (29.499 > GFR ≥ 15) (Prepolicy: 21, Postpolicy: 15), and 9 (0.3%) in Stage 5 (15 > GFR) (Prepolicy: 4, Postpolicy: 5). The primary outcome was 1-year and 2-year post-HT survival. RESULTS: There were 2863 patients who met the study criteria (1422 prepolicy, 1441 postpolicy). Overall survival, regardless of CKD stage, was lower following the policy change (p < 0.01). There was a similar risk of primary graft failure (PGF) in the pre- and postpolicy period (1.8% vs. 1.2%, p = 0.26). 1-year overall survival was 93% (91, 94) and 89% (87, 91) in the pre- and postpolicy periods, respectively. 2-year overall survival was 89% (88, 91) and 85% (82, 87) in the pre- and postpolicy periods, respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 1 -year survival was 93% (91, 95), 92% (90,93), 89% (86, 91), 89% (86, 93), 80% (68, 94), and 100% (100, 100), respectively. For CKD Stages 1, 2, 3a, 3b, 4, and 5, 2-year survival was 91% (88, 93), 88% (86, 90), 84% (81, 88), 84% (80, 89), 73% (59, 90), and 100% (100, 100), respectively. Patients with CKD 1 and 2 had better survival compared to those with CKD 3 (p < 0.01) and CKD 4 and 5 (p = 0.03) in the pre- and postpolicy periods. Patients with CKD 3 did not have a survival advantage over those with CKD 4 and 5 (p = 0.25). On cox regression analysis, advancing degrees of CKD were associated with an increased risk of mortality. CONCLUSIONS: Patients with LVAD support had decreased overall survival after the OPTN policy change. Patients with more advanced CKD had lower survival than patients without advanced CKD, though they were not impacted by the OPTN policy change.


Asunto(s)
Trasplante de Corazón , Corazón Auxiliar , Insuficiencia Renal Crónica , Obtención de Tejidos y Órganos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Obtención de Tejidos y Órganos/métodos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/mortalidad , Adulto , Tasa de Filtración Glomerular , Estados Unidos/epidemiología , Listas de Espera/mortalidad , Bases de Datos Factuales , Anciano , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía
3.
Artif Organs ; 48(10): 1162-1167, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38887186

RESUMEN

BACKGROUND: An inflammatory milieu after left ventricular assist device (LVAD) implantation is associated with multi-organ dysfunction and pre-operative heightened inflammatory state is associated with right ventricular failure after LVAD implantation. METHODS: We performed a retrospective analysis of 30 LVAD patients in our institution within the last 2 years for the development of fever and compared them to 30 non-LVAD open-heart surgery patients. RESULTS: Our results suggest that patients undergoing LVAD implantation are more likely to develop fever in the immediate post-operative period compared to other open-heart surgeries. This is independent of pharmacological treatment, age, or ethnical background. Females and obese patients were more likely to develop fever. CONCLUSION: Patients with right ventricular dysfunction, as demonstrated by elevated central venous pressure (CVP), had the strongest correlation with fever development. These results pose the question if there is a systemic inflammatory response-like phenomenon driven by increased right ventricular dysfunction.


Asunto(s)
Fiebre , Corazón Auxiliar , Síndrome de Respuesta Inflamatoria Sistémica , Disfunción Ventricular Derecha , Humanos , Corazón Auxiliar/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/fisiopatología , Fiebre/etiología , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Anciano , Adulto , Complicaciones Posoperatorias/etiología , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/etiología , Presión Venosa Central
4.
Artif Organs ; 48(6): 577-585, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38577853

RESUMEN

PURPOSE: LVAD outflow graft stenosis continues to remain prevalent with a high complication rate. We sought to pool the existing evidence on indications, utilization patterns, and outcomes of transcatheter interventions for outflow graft stenosis in the HeartMate 3 LVAD. METHODS: An electronic search was performed to identify all studies in the English literature reporting on HeartMate 3 LVAD outflow graft stenting. Patient-level data were extracted for analysis. RESULTS: Thirteen published reports and one unpublished case comprising a total of 28 patients were included. Median patient age was 68.5 years [Interquartile range: 58, 71] and 25.9% (7/27) were female. Dyspnea [60.7% (17/28)] was the most common presenting symptom. Low flow alarms were present in 60% (15/25) of patients. Findings included external compression [35.7% (10/28)], graft twist [21.4% (6/28)], graft twist and external compression [14.3% (4.28)], intraluminal thrombus [10.7% (3/28)], graft twist and intraluminal thrombus [3.6% (1/28)], and pseudoaneurysm of outflow graft [3.6% (1/28)]. Median time from LVAD implantation to stenting was 2.1 years [1.4, 3]. Immediate flow normalization after stenting was observed in 85.7% (24/28). The 30-day mortality was 12% (3/25). Overall mortality was 12% (3/25) at a median follow-up of 3.9 months [1, 17]. CONCLUSION: Outflow graft stenting in the HeartMate 3 LVAD appears to be a reasonable treatment option for outflow graft stenosis, with low overall rates of complications and mortality. Further refinement of indications and approaches may improve outcomes.


Asunto(s)
Corazón Auxiliar , Stents , Humanos , Corazón Auxiliar/efectos adversos , Stents/efectos adversos , Resultado del Tratamiento , Insuficiencia Cardíaca/cirugía , Femenino , Persona de Mediana Edad , Anciano , Masculino
5.
Artif Organs ; 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39345047

RESUMEN

PURPOSE: We sought to investigate the clinical results of preemptive temporary right ventricular assist device (RVAD) placement with left ventricular assist device (LVAD) implantation for anticipated right ventricular failure. METHODS: Patients at risk for right ventricular failure were identified by the heart team. After median sternotomy, Protekduo (LivaNova, London, UK) dual-stage cannula was inserted from the right internal jugular vein under fluoroscopy guidance, and advanced into the pulmonary artery to the bifurcation of the main pulmonary artery. This was then connected to the venous drainage from the right atrium for cardiopulmonary bypass (CPB). After LVAD implantation, we connected the Protekduo cannula to the RVAD with oxygenator, and weaned CPB. RESULTS: A total of 17 patients have received BiVAD implantation with this technique. The median age of patients was 55 years [Interquartile range (IQR): 51-63.5] and 94% (16/17) patients were male. 63.6% (7/11) of the patients were INTERMACS profile 1 or 2. Preoperatively, the median pulmonary artery pulsatility index was 4.0 [1.5-4.9] and median right ventricular stroke work index was 454.1 g/m/beat/m2 [436.5-530.2]. Postoperatively, the oxygenators were removed on median postoperative day (POD) 3.5 [3 - 5]. Patients received mechanical ventilation for a median of 4 days [1.5-12] and RVADs were explanted on median POD 8 [7-19] at bedside with local anesthesia. Median ICU stay was 15 days [11.4-24]. Perioperative complications included delayed sternal closure [54.5% (6/11)], re-exploration for bleeding [18% (2/11)], acute kidney injury [36% (4/11)], and heparin induced thrombocytopenia [18% (2/11)]. 30-day mortality was 0% (0/11) and 1 year survival was 85.9%. CONCLUSION: Preemptive temporary RVAD implantation strategy for right heart failure post-LVAD showed acceptable clinical outcomes without any 30-day mortality.

6.
Clin Transplant ; 37(8): e14906, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36610020

RESUMEN

Solid organ transplant candidates encountered increased wait times and mortality rates during the coronavirus 2019 (COVID-19) pandemic. Despite improvement in medical management and vaccination efficacy, this patient population remains at increased risk for complications post COVID-19 including organ rejection. We describe the development of antibody mediated rejection with or without cellular rejection in heart transplant (HT) recipients and previous COVID-19 infection or vaccination. Although centers have changed their management of outpatient follow-up for orthotopic heart transplant patients, little is known on surveillance of rejection and management of HT recipients after COVID-19 infection. We recommend frequent surveillance for rejection or allograft dysfunction after COVID-19 infection. We have adopted a transplant surveillance protocol for HT recipients with COVID-19 infection, given our recent experience with transplanted patients affected of COVID-19.


Asunto(s)
COVID-19 , Trasplante de Corazón , Trasplante de Órganos , Humanos , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , COVID-19/epidemiología , COVID-19/etiología , Trasplante Homólogo
7.
Artif Organs ; 47(4): 761-769, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36305738

RESUMEN

BACKGROUND: It is well established that percutaneous coronary intervention (PCI) is a life-saving procedure for acute myocardial infarction (AMI) in the general population and is guideline-recommended for both STEMI and NSTEMI. There is little literature regarding its use in patients with a pre-implanted Left Ventricular Assist Device (LVAD). METHODS: We retrospectively analyzed data from the National Inpatient Sample (NIS) Database to select all US adult patients (>18 years) with an LVAD diagnosed with an AMI divided into two groups; those who received PCI during the hospitalization and those who did not. RESULTS: A total of 3722 LVAD patients with AMI were identified, of these 17% of patients received PCI and 83% did not. After propensity matching of LVAD patients with AMI, there were 626 patients who received PCI and 623 who did not. Of patients receiving PCI, 37.5% had a STEMI while 29.7% of patients who did not receive PCI had STEMI. Rates of kidney injury (36.5% vs. 43.3%, OR 0.75, 95% CI 0.60-0.94, p = 0.016), sepsis (3.2% vs. 11.4%, OR 0.26, 95% CI 0.15-0.43, p < 0.001), cardiogenic shock (44.1% vs. 50.4%, OR 0.78, 95% CI 0.62-0.97, p = 0.03) and mortality (17.4% vs. 28.9%, OR 0.52, 95% CI 0.40-0.68, p < 0.001) were all better for patients receiving PCI. Vascular complications (1.4% vs. 0%, p = 0.008) and intracerebral hemorrhage (ICH) (1.6% vs. 0, p = 0.004) were both more common in the group receiving PCI. CONCLUSIONS: In this study, patients supported by LVAD with AMI had an elevated risk of mortality compared to generally accepted mortality rates of patients without LVAD. In this analysis PCI was associated with a decreased risk of mortality, cardiogenic shock, and kidney injury while increasing the risk for vascular complications and intracranial hemorrhage.


Asunto(s)
Corazón Auxiliar , Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Choque Cardiogénico/cirugía , Choque Cardiogénico/complicaciones , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/cirugía , Estudios Retrospectivos , Intervención Coronaria Percutánea/efectos adversos , Corazón Auxiliar/efectos adversos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/cirugía , Resultado del Tratamiento
8.
Artículo en Inglés | MEDLINE | ID: mdl-37196673

RESUMEN

BACKGROUND: Several factors affect heart transplant (HTx) and lung transplant (LTx) program outcomes. Variabilities in institutional and community characteristics have been shown to influence survival. At present, half of HTx centers in the United States do not possess a concomitant LTx program. This study sought to better understand the characteristics of HTx with and without LTx programs. METHODS: Nationwide transplant data were collected from the Scientific Registry of Transplant Recipients (SRTR) in August 2020. SRTR star rating ranges from tier 1 (lowest) to tier 5 (highest). HTx volumes and SRTR star ratings for survival were compared between the centers with heart-only (H0) programs and the centers with heart-lung (HL) programs. RESULTS: SRTR star ratings were available for 117 transplant centers with one or more HTx reported. The median number of HTx performed over 1 year was 16 (interquartile range [IQR]: 2-29). The number of HL centers (n = 67, 57.3%) were comparable to H0 centers (n = 50, 42.7%; p = 0.14). The HTx volume at the HL centers (28 [IQR: 17-41]) exceeded the HTx volume at the H0 centers (13 [IQR: 9-23]; p < 0.01), but were comparable to the LTx volume at the HL centers (31 [IQR: 16-46]; p = 0.25). The median HTx one-year survival rating was 3 (IQR: 2-4) at both the H0 and HL centers (p = 0.85). The HTx and LTx volumes were positively associated with the respective 1-year survivals (p < 0.01). CONCLUSION: While the presence of an LTx program is not directly associated with HTx survival, it has a positive association with the HTx volume. The HTx and LTx volumes are positively associated with the 1-year survival.

9.
Clin Transplant ; 36(2): e14567, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34927287

RESUMEN

PURPOSE: Heparin-induced thrombocytopenia (HIT) presents a unique challenge in patients requiring orthotopic heart transplantation (OHT). We sought to pool the existing evidence in a systematic review. METHODS: Electronic search was performed to identify all relevant studies on OHT in patients with HIT. Patient-level data for 33 patients from 21 studies were extracted for statistical analysis. RESULTS: Median patient age was 51 [IQR 41, 55] years, with 75.8% (25/33) males. All patients had a clinical diagnosis of HIT, and anti-PF4/Heparin antibodies were positive in 87.9% (29/33). Median lowest reported platelet count was 46 × 109 /L [27.2, 73.5]. Intraoperatively, 61% (20/33) of patients were given unfractionated heparin (UFH), while 39% (13/33) were given alternative anticoagulants. The alternative agent subgroup required more antifibrinolytics [54% (7/13) vs 10% (2/20), P = .02] and clotting factors [69.2% (9/13) vs 15.0% (3/20), P < .01]. Perioperative thrombosis occurred more [53.8% (7/13) vs 0% (0/20, P < .01) in alternate agent subgroup. More patients in the alternate agent subgroup required post-operative transfusions [54% (7/13) vs 0% (0/20), P < .01]. Thirty-day mortality of 15.2% (5/33) was comparable between the subgroups. CONCLUSION: Heparin use during OHT may be associated with less adverse effects compared to use of other anticoagulants with no difference in 30-day mortality.


Asunto(s)
Trasplante de Corazón , Trombocitopenia , Trombosis , Anticoagulantes/efectos adversos , Heparina/efectos adversos , Humanos , Masculino , Trombocitopenia/inducido químicamente
10.
Clin Transplant ; 36(5): e14598, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35048435

RESUMEN

STUDY: There is no widely accepted donor to recipient size-match metric to predict outcomes in cardiac transplant. The predictive ability of size-match metrics has not been studied when recipients are stratified by heart failure etiology. We sought to assess the performance of commonly used size metrics to predict survival after heart transplant, accounting for restrictive versus non-restrictive pathology. METHODS: The UNOS registry was queried from 2000 to 2017 for all primary isolated heart transplants. Donor-recipient ratios were calculated for commonly used size metrics and their association with survival was assessed using continuous, nonlinear analysis. RESULTS: 29 817 patients were identified. Height (P < .001), predicted heart mass (PHM) (P = .003), ideal body weight (IBW) (P < .001) and body mass index (BMI) (P = .003) ratios were significantly associated with survival, while weight and body surface area (BSA) ratios were not. When stratified, only BMI ratio retained significance for both restrictive (P = .051) and non-restrictive (P = .003) subsets. Recipients with restrictive etiology had increased risk of mortality with both a lower and higher BMI ratio. CONCLUSIONS: While many metrics show association with survival in the non-restrictive subset, BMI is the only metric that retains significance in the restrictive subset. Recipients with restrictive and non-restrictive etiologies of heart failure tolerate size mismatch differently.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Obtención de Tejidos y Órganos , Benchmarking , Supervivencia de Injerto , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/efectos adversos , Humanos , Tamaño de los Órganos , Estudios Retrospectivos , Donantes de Tejidos
11.
Artif Organs ; 46(12): 2478-2485, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35943857

RESUMEN

INTRODUCTION: Ventricular arrhythmias (VAs) are common after left ventricular assist device (LVAD) implantation though data are mixed on whether these events have an impact on mortality. METHODS: The National Inpatient Sample (NIS) database from 2002-2019 was queried for LVAD implantation admissions. Secondary ICD codes were analyzed to assess for the occurrence of VAs during this admission. Propensity score matching (PSM) was used to control for confounding variables between those with versus without VAs. RESULTS: The NIS database from 2002-2019 contained 43 936 admissions with LVAD implantation. VAs occurred in 19 985 (45.4%) patients. After PSM, the study cohort consisted of 39 989 patients, 19 985 (50.0%) of which had a secondary diagnosis of VA during the admission. When compared to those without VA, those with VA were at no higher risk for in-hospital mortality (adjusted odds ratio 1.011, 99.9% CI 0.956-1.069, p = 0.699). Those with a VA were at higher risk for cardiogenic shock and requiring mechanical ventilation, tracheostomy, and percutaneous endoscopic gastrostomy placement. Patients with a VA were also at lower risk for device thrombosis. Conversely, the VA group was at no higher risk for stroke. In comparing trends from 2002 to 2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased during this same period. CONCLUSION: In this retrospective study of the NIS database, VAs were common (45.4%) during the LVAD implantation admission. However, the occurrence of VAs during the implantation admission did not alter in-hospital mortality. More longitudinal studies are required to assess the long-term impact of VAs on mortality. In comparing trends from 2002-2019, the incidence of VAs has increased, while the mortality rate of those with and without VAs has decreased.


Asunto(s)
Insuficiencia Cardíaca , Corazón Auxiliar , Humanos , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Arritmias Cardíacas/etiología , Incidencia , Resultado del Tratamiento
12.
Artif Organs ; 45(7): 696-705, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33350485

RESUMEN

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.


Asunto(s)
Remoción de Dispositivos , Corazón Auxiliar/efectos adversos , Falla de Equipo , Insuficiencia Cardíaca/terapia , Humanos , Infecciones/complicaciones , Accidente Cerebrovascular/etiología , Trombosis/complicaciones
14.
N Engl J Med ; 369(9): 819-29, 2013 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-23984729

RESUMEN

BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).


Asunto(s)
Neuropatías Amiloides Familiares/terapia , Prealbúmina/genética , ARN Interferente Pequeño/uso terapéutico , Adolescente , Adulto , Neuropatías Amiloides Familiares/genética , Animales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Liposomas , Macaca fascicularis , Masculino , Nanocápsulas , Prealbúmina/metabolismo , ARN Interferente Pequeño/administración & dosificación , Adulto Joven
15.
Am Heart J ; 170(6): 1086-91, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26678629

RESUMEN

BACKGROUND: Cardiac allograft vasculopathy is a major cause of morbidity and mortality following heart transplantation. Large multicenter studies evaluating the clinical characteristics and inhospital outcomes of heart transplant recipients undergoing percutaneous coronary intervention (PCI) are lacking. OBJECTIVE: To evaluate the clinical characteristics, treatment patterns and inhospital outcomes of heart transplant recipients undergoing PCI compared to general population. METHODS: We analyzed 1,897,328 patients from the National Cardiovascular Data Registry CathPCI registry who underwent PCI of at least 1 native vessel between July 2009 and December 2013 from 1,477 centers, of which 542 patients (0.03%) were heart transplant recipients. Clinical characteristics were evaluated and, after 1:4 propensity matching, inhospital outcomes were compared between 538 heart transplant patients and 2,128 non-transplant patients. RESULTS: Transplant recipients undergoing PCI had a higher prevalence of diabetes, dyslipidemia and peripheral vascular disease; lower prevalence of angina, acute coronary syndrome, abnormal noninvasive functional study, and type C coronary lesions compared to the non-transplant PCI population. After propensity matching, all-cause inhospital mortality was similar between transplant and non-transplant groups (1.3% vs 1.0%; OR, 1.21; 95% CI, 0.54-2.67). CONCLUSION: This is the largest series to date outlining the characteristics of heart transplant recipients undergoing PCI. Similar inhospital outcomes were noted in heart transplant recipients compared to the general population. Further studies evaluating long-term outcomes are warranted.


Asunto(s)
Aloinjertos , Enfermedad de la Arteria Coronaria , Trasplante de Corazón/efectos adversos , Intervención Coronaria Percutánea , Complicaciones Posoperatorias , Enfermedades Vasculares , Adulto , Anciano , Aloinjertos/irrigación sanguínea , Aloinjertos/patología , Comorbilidad , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Humanos , Efectos Adversos a Largo Plazo/epidemiología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Sistema de Registros , Estados Unidos/epidemiología , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/cirugía
16.
Curr Probl Cardiol ; 49(4): 102406, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38237814

RESUMEN

BACKGROUND: Pulmonary Hypertension (PH) is a sequela of arteriovenous (AV) fistulas (AVF) or AV grafts (AVG) in patients with end-stage kidney disease (ESKD) due to the creation of shunt physiology and increased pulmonary blood flow. PH has been consistently associated with increased mortality but there is a paucity of data regarding management. RESEARCH QUESTION: The objective of this study was to identify risk factors and outcomes in patients who develop PH after AVF or AVG creation for hemodialysis access. METHODS: Using the United States Renal Data System, we identified all patients over age 18 initiated on dialysis from 2012-2019 who did not receive renal transplant. We identified a) the predictors of PH in patients with ESKD on hemodialysis; b) the independent mortality risk associated with development of PH. RESULTS: We identified 478,896 patients initiated on dialysis from 2012-2019 of whom 27,787 (5.8 %) had a diagnosis of PH. The median age was 65 (IQR: 55-74) years and 59.1 % were male. Reduced ejection fraction, any congestive heart failure, obstructive sleep apnea, and female sex were the strongest predictors of PH diagnosis. Both AVG and AVF were also associated with an increased rate of PH diagnosis compared to catheter-based dialysis (p < 0.001). PH portended a poor prognosis and was associated with significantly increased mortality (p < 0.001). CONCLUSIONS: Patients with AVF or AVG should be screened using echocardiography prior to creation and monitored with serial echocardiography for the development of PH, and if present, considered for revision of the AVA. This is also the first study to identify that AVG are a risk factor for PH in dialysis patients.


Asunto(s)
Hipertensión Pulmonar , Fallo Renal Crónico , Humanos , Femenino , Masculino , Anciano , Adolescente , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Riñón , Progresión de la Enfermedad
17.
Cureus ; 16(6): e62477, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39015863

RESUMEN

Introduction Data regarding clinical outcomes after transcatheter aortic valve replacement (TAVR) vs surgical aortic valve replacement (SAVR) in patients with sarcoidosis is lacking. This study aims to clarify the clinical outcomes of TAVR vs SAVR in patients with sarcoidosis. Methods Data was collected from the National Inpatient Sample database from 2016-2019 using validated ICD-10-CM codes for sarcoidosis, TAVR, and SAVR. Patients were divided into two cohorts: those who underwent TAVR and those who underwent SAVR. Statistical analysis was performed using Pearson's chi-squared test to determine clinical outcomes of TAVR vs SAVR in patients with sarcoidosis. Results The prevalence of sarcoidosis was 0.23% among total study patients (n=142,420,378). After exclusions, the prevalence of TAVR was 650 (49%) and SAVR was 675 (51%) in patients with sarcoidosis. Patients who underwent TAVR were on average older (74 vs 65 years old, p=0.001), and more likely to be female (57 vs 40%, p<0.001) compared to patients who underwent SAVR. The TAVR cohort had higher rates of congestive heart failure (CHF) (77.7 vs 42.2%, p=0.001), chronic kidney disease (CKD) (42.3 vs 24.4% p=0.001), anemia (5.4 vs 2.2%, p=0.004), percutaneous coronary intervention (PCI) (1.5 vs 0%, p=0.004), and hypothyroidism (31.5 vs 16.3%, p=0.001) compared to the SAVR cohort. Inpatient mortality post-procedure was higher in the SAVR cohort compared to the TAVR cohort (15 vs 0, p=0.001). Regarding post-procedure complications, respiratory complications were more common in the SAVR cohort (4.4 vs 0%, p=0.001), while TAVR was associated with a higher incidence of permanent pacemaker (PPM) insertion (2.15 vs 0.8%, p=0.001). There was no statistical difference in the development of acute kidney injury (AKI) (0.8 vs 1.5%, p=0.33), AKI requiring hemodialysis (0 vs. 0.7%, p=0.08), or stroke (0.8 vs 0.7, p=1) post-procedure between the two cohorts. Conclusion This study found that in the sarcoidosis population, TAVR was associated with reduced mortality, shorter hospital length of stay, and lower hospitalization costs in comparison to SAVR.

18.
Artículo en Inglés | MEDLINE | ID: mdl-39361224

RESUMEN

BACKGROUND: While the effect of pre-transplant weight on patient outcomes following heart transplantation (HTx) has previously been studied, data regarding the impact of dynamic weight change prior to HTx are extremely limited. OBJECTIVES: We sought to elucidate the interaction between HTx listing weight and weight change while waitlisted, and explore how that interaction impacts post-HTx survival in a continuous manner. METHODS: Adult patients listed for HTx from 1987 to 2020 were identified from UNOS database. Three-dimensional restricted cubic spline analysis explored post-HTx survival relative to both changes in BMI/weight and BMI at time of HTx listing. Continuous predictor variables were analyzed with Cox proportional hazards method. RESULTS: 9,628 included patients underwent HTx. Median recipient age was 55 [IQR 46-62] years, and 21% were females. 53% of patients lost while 47% gained weight on the waitlist. Median BMI (27.6 kg/m2 [24.3-31.3] vs. 27.4 kg/m2 [24.2-30.9], paired p < 0.001) and weight (84.8 kg [73.0-98.0] kg vs. 84.4 kg [72.6-96.6], p < 0.001) were similar at listing and transplant. One-year survival was 89.3%. Weight loss over 3 BMI points or 10 kg was associated with higher hazard of death irrespective of listing BMI. In non-obese patients, some weight gain (1-4 BMI points or 5-15 kg) was associated with improved survival. In cachectic patients (BMI < 18.5), failure to gain weight was associated with worse survival. CONCLUSIONS: Impact of weight change varies depending on listing BMI. While a survival benefit is seen in non-obese patients who gain some weight, significant weight loss is associated with poorer survival.

19.
Crit Pathw Cardiol ; 23(2): 81-88, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38768050

RESUMEN

PURPOSE: We sought to characterize adaptive changes to the revised United Network for Organ Sharing donor heart allocation policy and estimate long-term survival trends for heart transplant (HTx) recipients. METHODS: Patients listed for HTx between October 17, 2013 and September 30, 2021 were identified from the United Network for Organ Sharing database, and stratified into pre- and postpolicy revision groups. Subanalyses were performed to examine trends in device utilization for extracorporeal membranous oxygenation (ECMO), durable left ventricular assist device (LVAD), intra-aortic balloon pump (IABP), microaxial support (Impella), and no mechanical circulatory support (non-MCS). Survival data post-HTx were fitted to parametric distributions and extrapolated to 5 years. RESULTS: We identified 27,523 HTx waitlist candidates during the study period, most of whom (n = 16,376) were waitlisted in the prepolicy change period. Overall, 19,554 patients underwent HTx during the study period (pre: 12,037 and post: 7517). Listings increased after the policy change for ECMO ( P < 0.01), Impella ( P < 0.01), and IABP ( P < 0.01) patients. Listings for LVAD ( P < 0.01) and non-MCS ( P < 0.01) patients decreased. HTx increased for ECMO ( P < 0.01), Impella ( P < 0.01), and IABP ( P < 0.01) patients after the policy change and decreased for LVAD ( P < 0.01) and non-MCS ( P < 0.01) patients. Waitlist survival increased for the overall ( P < 0.01), ECMO ( P < 0.01), IABP ( P < 0.01), and non-MCS ( P < 0.01) groups. Waitlist survival did not differ for the LVAD ( P = 0.8) and Impella ( P = 0.1) groups. Post-transplant survival decreased for the overall ( P < 0.01), LVAD ( P < 0.01), and non-MCS ( P < 0.01) populations. CONCLUSIONS: Allocation policy revisions have contributed to greater utilization of ECMO, Impella, and IABP, decreased utilization of LVADs and non-MCS, increased waitlist survival, and decreased post-HTx survival.


Asunto(s)
Bases de Datos Factuales , Trasplante de Corazón , Obtención de Tejidos y Órganos , Listas de Espera , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estados Unidos/epidemiología , Listas de Espera/mortalidad , Adulto , Corazón Auxiliar/estadística & datos numéricos , Donantes de Tejidos/provisión & distribución , Tasa de Supervivencia/tendencias , Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Estudios Retrospectivos , Contrapulsador Intraaórtico/estadística & datos numéricos
20.
Antimicrob Agents Chemother ; 57(8): 3568-75, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23669390

RESUMEN

Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against A. baumannii in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of A. baumannii was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic A. baumannii. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a ≥ 2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of A. baumannii.


Asunto(s)
Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Cetilpiridinio/farmacología , Farmacorresistencia Bacteriana Múltiple , Nanotecnología/métodos , Carga Bacteriana , Biopelículas/efectos de los fármacos , Estabilidad de Medicamentos , Sinergismo Farmacológico , Emulsiones/química , Etanol/farmacología , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Octoxinol/farmacología , Tamaño de la Partícula , Cloruro de Sodio/farmacología , Aceite de Soja/farmacología
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