Sensitization during short-term mechanical circulatory support. Determinants, therapeutic management, and outcomes after heart transplant.

INTRODUCTION AND OBJECTIVES: The development of human-leukocyte antigen antibodies is a well-known adverse effect of the use of long-term ventricular assist devices (VADs). The aim of this study was to determine the incidence of sensitization during short-term mechanical circulatory support with VAD (CentriMag), its determinants, and its impact on posttransplant outcomes. METHODS: We performed a retrospective review of patients who were bridged to transplant with short-term VAD from 2009 to 2019. Sensitization was defined as a calculated panel-reactive antibody> 10%. The endpoints included overall survival and rejection-free survival. RESULTS: A total of 89 patients (median age 56.0 [interquartile range, 50.0-59.9] years, 16.8% female) received a short-term VAD as a bridge to transplant. The median duration of support was 23.6 [interquartile range, 16.6-35.0] days. Eleven patients (12.4%) became sensitized during support. The only factor significantly associated with sensitization was female sex (OR, 8.67; 95%CI, 1.93-38.8; P=.005). Of the 89 patients, 21 patients died during support; 68 patients underwent heart transplant. After a mean follow-up of 49.6 ±31.2 months, 8 patients (11.8%) died and 20 (29.4%) had at least 1 rejection episode. On multivariate analysis, sensitization was an independent predictor of acute rejection (HR, 3.64; 95%CI, 1.42-9.33; P=.007), with a nonstatistically significant trend to higher mortality (HR, 4.07; 95%CI, 0.96-17.3; P=.057). CONCLUSIONS: Sensitization with short-term VADs can occur and is significantly associated with female sex and with rejection. Sensitization also showed a nonstatistically significant trend to higher mortality.

Biologically driven cut-off definition of lymphocyte ratios in metastatic breast cancer and association with exosomal subpopulations and prognosis.

High neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) are respectively associated with systemic inflammation and immune suppression and have been associated with a poor outcome. Plasmatic exosomes are extracellular vesicles involved in the intercellular communication system that can exert an immunosuppressive function. Aim of this study was to investigate the interplay between the immune system and circulating exosomes in metastatic breast cancer (MBC). A threshold capable to classify patients according to MLR, NLR and PLR, was computed through a receiving operator curve analysis after propensity score matching with a series of female blood donors. Exosomes were isolated from plasma by ExoQuick solution and characterized by flow-cytometry. NLR, MLR, PLR and exosomal subpopulations potentially involved in the pre-metastatic niche were significantly different in MBC patients with respect to controls. MLR was significantly associated with number of sites at the onset of metastatic disease, while high levels of MLR and NLR were found to be associated with poor prognosis. Furthermore, exosomal subpopulations varied according to NLR, MLR, PLR and both were associated with different breast cancer subtypes and sites of distant involvement. This study highlights the nuanced role of immunity in MBC spread, progression and outcome. Moreover, they suggest potential interaction mechanisms between immunity, MBC and the metastatic niche.

Trends in cardiogenic shock management and prognostic impact of type of treating center.

INTRODUCTION AND OBJECTIVES: Current guidelines recommend centralizing the care of patients with cardiogenic shock in high-volume centers. The aim of this study was to assess the association between hospital characteristics, including the availability of an intensive cardiac care unit, and outcomes in patients with ST-segment elevation myocardial infarction (STEMI)-related cardiogenic shock (CS). METHODS: Discharge episodes with a diagnosis of STEMI-related CS between 2003 and 2015 were selected from the Minimum Data Set of the Spanish National Health System. Centers were classified according to the availability of a cardiology department, catheterization laboratory, cardiac surgery department, and intensive cardiac care unit. The main outcome measured was in-hospital mortality. RESULTS: A total of 19 963 episodes were identified. The mean age was 73.4±11.8 years. The proportion of patients with CS treated at hospitals with a catheterization laboratory and cardiac surgery department increased from 38.4% in 2005 to 52.9% in 2015 (P <.005). Crude- and risk-adjusted mortality rates decreased over time, from 82% to 67.1%, and from 82.7% to 66.8%, respectively (both P <.001). Coronary revascularization, either percutaneous or coronary artery bypass grafting, was independently associated with a lower mortality risk (OR, 0.29 and 0.25; both P <.001, respectively). Intensive cardiac care unit availability was associated with lower adjusted mortality rates (65.3%±7.9 vs 72±11.7; P <.001). CONCLUSIONS: The proportion of patients with STEMI-related CS treated at highly specialized centers increased while mortality decreased during the study period. Better outcomes were associated with the increased performance of revascularization procedures and access to intensive cardiac care units over time.

Background, incidence, and predictors of antiplatelet therapy discontinuation during the first year after drug-eluting stent implantation.

BACKGROUND: Predictors of antiplatelet therapy discontinuation (ATD) during the first year after drug-eluting stent implantation are poorly known. METHODS AND RESULTS: This was a prospective study with 3-, 6-, 9-, and 12-month follow-up of patients receiving at least 1 drug-eluting stent between January and April 2008 in 29 hospitals. Individual- and hospital-level predictors of ATD were assessed by hierarchical-multinomial regression analysis. ATD could be assessed in 1622 candidates for follow-up (82.5%). A total of 234 patients (14.4%) interrupted at least 1 antiplatelet therapy drug, predominantly clopidogrel (n=182, 11.8%). Bleeding events or invasive procedures led to ATD in 109 patients. This was predicted by renal impairment (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.48 to 5.34), prior major hemorrhage (OR 3.77, 95% CI 1.41 to 10.03), and peripheral arterial disease (OR 1.78, 95% CI 1.01 to 3.15). Medical decisions led to ATD in 70 patients; this was predicted by long-term use of anticoagulant therapy (OR 3.88, 95% CI 1.26 to 11.98), undergoing the procedure in a private hospital (OR 13.3, 95% CI 1.69 to 105), and not receiving instructions about medication (OR 2.8, 95% CI 1.23 to 6.36). Thirty-nine patients interrupted ATD on their own initiative, mainly immigrants (OR 3.78, 95% CI 1.2 to 11.98) and consumers of psychotropic drugs (OR 2.58, 95% CI 1.3 to 5.12). CONCLUSIONS: ATD during the first year after drug-eluting stent implantation is based mainly on patient decision or a medical decision not associated with major bleeding events or major surgical procedures. Individual- and hospital-level variables are important to predict ATD.

Impact of drug eluting stents on the clinical practice of revascularisation of coronary artery disease.

AIMS: Drug-eluting stents (DES) have shown to reduce restenosis rates in all lesional subsets. This has expanded the application of percutaneous intervention (PCI). In this study we address the impact of the high DES penetration on the management of patients referred for coronary angiography. METHODS AND RESULTS: We have studied the cohorts of patients referred for coronary angiography in 2000-2001 prior to DES availability, and in 2005-2006 with a 73% DES implementation. In 2000-1 of 2,458 coronary angiographic studies, 84% had significant lesions (>50%), 56% had PCI, 8.8% had CABG and in 443 (18%) with significant lesions no revascularisation was attempted. In 2005-6 out of 2,600 angiographies, 84% had significant lesions, 64% had PCI, 6% had CABG and in 312 (12%) with significant lesions no revascularisation was done. The increase in PCI, the reduction in CABG and the decrease in non-revascularised diseased cases were all significant (p<0,001). The PCI and CABG groups in 2005-6 compared to 2000-1 had a more complex lesion profile with, however, less in-stent restenotic lesions treated (10% vs 4.2%; p<0.001). CONCLUSIONS: The wide clinical introduction of DES was associated with a significant increase in patients undergoing any kind of revascularisation, increasing the PCI volume to the detriment of CABG activity. Patients with PCI in 2006 had more complex lesions treated, whereas restenosis was less frequent.

[Prospective use of an intravascular ultrasound-derived minimum lumen area cut-off value in the assessment of intermediate left main coronary artery lesions]. / Aplicación prospectiva de un valor de corte de área luminal mínima por ecografía intravascular en la evaluación de lesiones intermedias del tronco.

BACKGROUND AND OBJECTIVES: Angiographic assessment of the severity of intermediate lesions in the left main coronary artery (LMCA) is subject to significant limitations. Intravascular ultrasound (IVUS) can provide accurate measurement, but there is no agreement on the minimum lumen cross-sectional area (MLA) that indicates significant disease. The aim of this study was to determine the long-term safety of applying a cut-off value of 6 mm2 for the MLA in the LMCA. METHODS: The study included patients with intermediate lesions (i.e., 25-50%) in unprotected LMCAs, with no previous evidence of associated ischemia. An IVUS examination was carried out and revascularization was indicated when the MLA was < or =6 mm2. RESULTS: In total, 79 patients were recruited between 2000-2005. In 31 (39%), the MLA was < or =6 mm2, and they underwent LMCA revascularization; in the remaining 48 (61%), the MLA was >6 mm2, and patients either underwent angioplasty for other lesions (n=37) or continued medical treatment (n=11). In a follow-up period of 40 [17] months, four patients (8.3%) died from heart disease, all of whom had an MLA between 9-10 mm2 in the baseline study. Revascularization of the LMCA was necessary in only two patients (4.2%), both of whom had elective surgery more than 2 years after the initial study. CONCLUSIONS: Intravascular ultrasound assessment of intermediate LMCA lesions using an MLA cut-off value of 6 mm2 appears safe over the long term provided the clinical and angiographic criteria applied to patient selection are similar to those used in this study.

[Two-year clinical follow-up in 200 patients receiving sirolimus-eluting stents in lesions at a high risk of restenosis]. / Seguimiento clínico a 2 años de 200 pacientes tratados con stent liberador de rapamicina en lesiones de alto riesgo de reestenosis.

INTRODUCTION AND OBJECTIVES: Sirolimus-eluting stents (SESs) have been shown to reduce the rate of restenosis significantly in all types of coronary lesion. However, reports of late cases of thrombosis and restenosis have raised questions about long-term outcome in patients treated with these stents. Our aim was to evaluate long-term outcome in patients undergoing SES placement in lesions at a high risk of restenosis. PATIENTS AND METHOD: Since SESs became available, we have used them to treat lesions at risk of restenosis. We studied clinical outcomes in consecutive patients treated with SESs who were followed up for more than 2 years. RESULTS: The study included 200 patients (age 60[11] years, 22% diabetics) who were treated between June 2002 and April 2003 for 309 lesions: 16% were total occlusions, 16.8% in-stent restenoses, 28% diffuse lesions, and 30% small-vessel lesions. The total stent length per patient was 29 (16) mm and the mean diameter was 2.78 (0.27) mm. In a mean clinical follow-up period of 29 (3.2) months (range 24-34 months), there were four deaths, two (1%) of which were cardiac, four (2%) non-fatal infarctions, four (2%) in-stent thromboses (all occurred late, at 3, 7, 26 and 31 months), four (2%) cases requiring target lesion revascularization (at 3, 5, 14 and 15 months), and six (3%) requiring revascularization of a new lesion. CONCLUSIONS: Long-term follow-up of patients undergoing SES placement in lesions at a high risk of restenosis revealed a very low restenosis rate. However, the incidence of late thrombosis appeared to be elevated and warrants further evaluation in larger studies.