RESUMEN
BACKGROUND: Bradyarrhythmias, requiring pacemaker (PM) implantation, are common complications following orthotopic heart transplantation (HTx). Currently used heart transplantation methods are primarily the bicaval technique and the total heart transplantation technique. The aim of the study was to assess the incidence and risk factors, including donor parameters, of conduction disorders requiring pacing after HTx. METHODS: A population of 111 (52 ± 13 years, 91 (82%) men) heart recipients was divided into a group requiring PM implantation post-HTx and a group not requiring PM. We compared groups in terms of donor parameters, time of graft ischemia, transport and transplantation, and surgical techniques as the potential risk factors for significant bradyarrhythmias. RESULTS: Ten of 111 patients with HTx (9%) required PM implantation. The indication in 7 cases was sinus node dysfunction (SND), in 3 patients it was complete atrioventricular block (AV-block). In the PM group, the age of 48 ± 6 vs 40 ± 11 years (P = .0227) and the body mass index (BMI) 28 ± 3 vs 26 ± 4 kg/m2 (P = .0297) of the donor were significantly higher. There was no influence of organ transport time, ischemia time, and transplantation time. All patients requiring PM implantation were transplanted using the bicaval anastomosis: 10 (100%) vs 71 (70%) in the group not requiring PM (P = .044). CONCLUSIONS: The need for PM implantation post-HTx despite using new techniques is still common, especially in the group operated with the bicaval method. In addition, higher donor's age and BMI are risk factors of PM implantation, what is of importance as qualification criteria of donor hearts have been gradually extended.
Asunto(s)
Trasplante de Corazón , Marcapaso Artificial , Humanos , Trasplante de Corazón/efectos adversos , Masculino , Factores de Riesgo , Femenino , Persona de Mediana Edad , Adulto , Incidencia , Bradicardia/epidemiología , Bradicardia/etiología , Estudios Retrospectivos , Donantes de TejidosAsunto(s)
Taponamiento Cardíaco , Verde de Indocianina , Derrame Pericárdico , Humanos , Masculino , Persona de Mediana Edad , Taponamiento Cardíaco/etiología , Taponamiento Cardíaco/diagnóstico por imagen , Taponamiento Cardíaco/cirugía , Derrame Pericárdico/diagnóstico por imagen , Derrame Pericárdico/cirugía , Derrame Pericárdico/etiologíaAsunto(s)
Trasplante de Corazón , Implantación de Prótesis de Válvulas Cardíacas , Corazón Auxiliar , Insuficiencia de la Válvula Mitral , Humanos , Choque Cardiogénico/etiología , Choque Cardiogénico/cirugía , Resultado del Tratamiento , Insuficiencia de la Válvula Mitral/complicaciones , Insuficiencia de la Válvula Mitral/cirugíaAsunto(s)
Trasplante de Corazón , Corazón Auxiliar , Insuficiencia de la Válvula Mitral , Humanos , Choque Cardiogénico/etiología , Choque Cardiogénico/cirugía , Insuficiencia de la Válvula Mitral/complicaciones , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral , Enfermedad Aguda , Resultado del TratamientoAsunto(s)
COVID-19 , Hemangiosarcoma , Embolia Pulmonar , Masculino , Humanos , Embolia Pulmonar/diagnóstico , Disnea/diagnóstico , Prueba de COVID-19RESUMEN
BACKGROUND: Balloon pulmonary angioplasty (BPA) has become a therapeutic option for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Despite significant improvement in the technique, treatment of subtotal (STO) and total (TO) pulmonary artery occlusions with BPA may pose risk, but the efficacy is less known. AIM: We aimed to evaluate the safety and efficacy of BPA in STO/TO. METHODS: We included consecutive patients with inoperable CTEPH, who underwent BPA treatment. To evaluate the efficacy and safety we grouped all BPA sessions into these in which recanalization of at least one STO or TO was performed and into those without. The primary efficacy outcome was a decrease of pulmonary vascular resistance (PVR) after BPA sessions with STO/TO recanalization as compared to those without. RESULTS: We analysed 169 BPA sessions in 50 CTEPH patients. Out of a total number of 831 lesions subjected for BPA, 169 were classified as STOs or TOs [123 (15,6%) and 39 (4,7%) respectively]. At least one STO/TO recanalization was successfully performed during 90 BPA sessions. Three (2,3%) STOs and 8 (20,5%) TOs were not recanalized despite repeated attempts. Recanalization of at least one STO/TO at the level of segmental pulmonary artery was associated with a significant PVR improvement as compared to subsegmental-only STO/TO recanalizations or no recanalizations (-126 ± 192 vs -38 ± 135 dyn·s·cm - 5, p = 0.007). The rate of complications was similar in STO/TO and non-STO/TO lesions (4.1% vs 2.4%, p = 0.22). CONCLUSIONS: The use of BPA for the recanalization of subtotal and total PA occlusions is safe and feasible. Recanalization of segmental occlusive lesions leads to a significant improvement in PVR as compared to dilatation of nonocclusive ones.
Asunto(s)
Angioplastia de Balón , Hipertensión Pulmonar , Embolia Pulmonar , Angioplastia de Balón/métodos , Enfermedad Crónica , Hemodinámica , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/cirugía , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagen , Resultado del TratamientoRESUMEN
INTRODUCTION AND IMPORTANCE: The majority of mediastinal tumours develop asymptomatically and are often detected incidentally on a chest X-ray performed for another reason. Mediastinal tumours, although mostly asymptomatic, may cause non-specific symptoms associated with advanced tumour growth. CASE PRESENTATION: We present a case of a 30-year-old woman who presented with exhaustion and lower back pain accompanied by severe headaches with symptoms of visual disturbances, followed by the typical Horner syndrome. Computed tomography revealed a tumour measuring 12 × 11 × 10 cm in the right cavity with features suggestive of teratoma. The patient underwent mediastinal tumour resection and thymectomy. The pathomorphological examination confirmed the primary diagnosis of mediastinal teratoma, but rare somatic type malignancy was detected. Therefore, the patient was referred for further oncological treatment. DISCUSSION: Mediastinal teratoma is an uncommon finding and usually asymptomatic. Despite its slow growth, it can grow enough to compress adjacent structures, causing symptoms similar to those presented in our patient. CONCLUSION: Radiologic imaging proves diagnostic in most cases. Despite the somatic type malignancy, surgical excision of the tumour using the en-bloc technique seems to be a sufficient option for the patient, and further oncological treatment is not always obligatory.
RESUMEN
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular mortality, but the mechanisms behind this remain unclear. Prothrombotic fibrin clot properties have been shown in T2DM and cardiovascular disease. We hypothesized that formation of denser clots, which are resistant to fibrinolysis, has a negative impact on cardiovascular mortality in T2DM. METHODS: We studied 133 T2DM patients aged 43-83 years. Plasma fibrin clot turbidity, permeation, compaction, and efficiency of clot lysis using 3 assays including the determination of maximum concentration (D-Dmax) and rate of increase in D-dimer concentration (D-Drate) released during tissue plasminogen activator-induced degradation, were evaluated at the time of enrollment, along with thrombin generation and fibrinolytic proteins. During a median follow-up period of 72 months, cardiovascular mortality was recorded. RESULTS: Cardiovascular deaths (n = 16, 12%) occurred more frequently in patients with increased D-Dmax (> 4.26 mg/l, hazard ratio [HR] 5.43, 95% confidence interval [CI] 1.99-14.79), or decreased D-Drate (< 0.07 mg/l/min, HR 2.97, 95% CI 1.07-8.23), or increased peak thrombin (> 283.5 nM, HR 5.65, 95% CI 2.07-15.51). These predictors had an even more potent impact on cardiovascular mortality in patients with prior cardiovascular disease (64.7%) and with corresponding risks as follows: HR 6.18, 95% CI 2.02-18.96; HR 8.98, 95% CI 2.99-26.96; and HR 5.35, 95% CI 1.62-17.72, respectively. Other investigated fibrin variables and fibrinolytic proteins did not associate with cardiovascular mortality. In multivariable analysis, cardiovascular mortality was predicted by D-Dmax > 4.26 mg/l, age > 65 years, prior cardiovascular disease, and C-reactive protein > 3 mg/l. CONCLUSIONS: This study is the first to show that formation of denser fibrin clots resistant to fibrinolysis could be a risk factor for long-term cardiovascular mortality in T2DM.
Asunto(s)
Coagulación Sanguínea , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/sangre , Fibrina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinólisis , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Factores de TiempoRESUMEN
OBJECTIVES: Long-term durability of bioprosthetic valves is predominantly limited by structural valve deterioration. RESILIA™ tissue has exhibited reduced calcification in pre-clinical and early clinical studies. This study evaluated the 5-year clinical and haemodynamic outcomes of an aortic valve with this tissue. METHODS: This was a prospective, non-randomized, single-arm study of 133 patients implanted with a RESILIA aortic bioprosthesis between July 2011 and February 2013 at 2 sites in Poland. Clinical outcomes and haemodynamic performance were assessed annually for 5 years post-implant. Safety events were adjudicated by a Clinical Events Committee and echocardiographic data were assessed by an independent core laboratory. RESULTS: Mean patient age was 65.3 ± 13.5 years, with 34 patients (25.6%) ≤60. The mean follow-up was 4.2 ± 1.5 years. Early (≤30 days) and late (>30 days) all-cause mortality were 2.3% (N = 3) and 3.2%/late patients-years (N = 18) respectively. Early events included thromboembolism in 3 patients (2.3%). Late valve-related events included endocarditis in 1 patient, which led to explant, and valve thrombosis in another patient. There were no events of structural valve deterioration throughout the study. At 5 years, mean gradient was 14.8 ± 7.6 mmHg and effective orifice area was 1.4 ± 0.5 cm2, a marked improvement over baseline values. All New York Heart Association class III patients and most class II patients at baseline had improved classifications at 5 years. CONCLUSIONS: The bioprosthesis with RESILIA tissue demonstrated a good safety profile with excellent haemodynamic performance over 5 years of follow-up. These encouraging outcomes warrant additional investigation of this novel tissue. CLINICAL TRIAL REGISTRATION NUMBER: NCT01651052.
Asunto(s)
Estenosis de la Válvula Aórtica , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Bioprótesis/efectos adversos , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Persona de Mediana Edad , Polonia , Estudios Prospectivos , Diseño de Prótesis , Resultado del TratamientoRESUMEN
BACKGROUND: The objective of this study was to compare the impact of skeletonized versus pedicled left internal mammary artery (LIMA) harvesting on bleeding after coronary artery bypass grafting (CABG). METHODS: In a randomized, single-blinded trial with a parallel group design and equal allocation, we randomly assigned 62 patients undergoing primary elective CABG in a tertiary cardiac center to skeletonized or pedicled LIMA dissection. Before surgery, all aspects of coagulation were assessed. Patients were blinded to LIMA dissection technique and monitored for cumulative drainage at 12 hours (primary outcome) as well as myocardial necrosis markers. RESULTS: With recruitment complete, there were 31 patients in each group; all patients were analyzed. Median postoperative drainage was 395 mL at 12 hours in all patients; it was lower by 28% at 12 hours (P = .02) in patients with skeletonized LIMA (Cohen's d, 0.6; 95% confidence interval (CI), 0.09-1.11). Patients with a LIMA pedicle received more fresh-frozen plasma transfusions than did the skeletonized LIMA group (Median 3; interquartile range 3-5 versus median 3; interquartile range 3-3; P = .03). Study arms did not differ in blood coagulation. Left internal mammary artery skeletonization (odds ratio = 0.04; 95% CI, 0.003-0.44; P = .009) and higher body mass index (odds ratio = 0.63; 95% CI, 0.45-0.89; P = .008) decreased the odds of being in the top drainage quartile at 12 hours (≥550 mL). Creatine kinase was lower in skeletonized LIMA directly after surgery (median 218 U/L; interquartile range 175-310 U/L versus median 424 U/L; interquartile range 256-510 U/L; P < .001), at 6 hours (median 324 U/L; interquartile range 239-424 U/L versus median 529 U/L; interquartile range 374-707 U/L; P < .001), and 12 hours after surgery (median 351 U/L; interquartile range 277-552 U/L versus median 695 U/L; interquartile range 509-1067 U/L; P < .001). CONCLUSIONS: Left internal mammary artery skeletonization results in lower mediastinal drainage after CABG than pedicled LIMA harvesting.
Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Puente de Arteria Coronaria/métodos , Arterias Mamarias/trasplante , Recolección de Tejidos y Órganos/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
BACKGROUND: The durability of bioprosthetic heart valves is limited by structural valve deterioration (SVD) due to long-term calcification. A novel bioprosthetic tissue (RESILIATM) has been developed which, in preclinical studies, has shown reduced calcification. The purpose of this study was to evaluate the intermediate-term clinical outcomes and hemodynamic performance of this tissue. METHODS: A prospective, single-arm, observational trial was conducted in patients who required surgical aortic valve replacement (AVR). Between July 2011 and February 2013, 133 patients were implanted at two sites in Poland. Hemodynamic performance and clinical outcomes were assessed annually through 4 years of follow-up. All safety events were adjudicated by an independent Clinical Events Committee, and echocardiographic data were evaluated by a core laboratory. RESULTS: Patients were 65.3±13.5 years old and 26% were ≤60 years old. The average follow-up was 3.8±1.1 (median: 4.1; IQR, 4.0-4.3) years. Early (≤30 day) and late (>30 day) all-cause mortality rates were 2.3% (n=3) and 3.2% late patient-years (n=16), respectively. There were no cases of early or late SVD. There was one early case of major paravalvular leak (0.8%), and no late cases. At 4 years, the mean gradient was 14.5±7.4 mmHg and the effective orifice area was 1.6±0.4 cm2, both markedly improved from baseline. At 4 years, the New York Heart Association functional class had improved from baseline in 54.5% of patients. CONCLUSIONS: The aortic bioprosthesis with novel RESILIATM tissue demonstrated excellent hemodynamic performance and safety outcomes over 4 years. Longer follow-up will be important to confirm the durability of this bioprosthesis.
RESUMEN
OBJECTIVES: On-pump coronary artery bypass grafting (CABG) is associated with elevated bleeding risk. Our aim was to evaluate the role of surgical experience in postoperative blood loss. METHODS: A propensity score-matched analysis was employed to compare on-pump CABG patients operated on by residents and specialists. End points included drainage volume and bleeding severity, as assessed by the Universal Definition of Perioperative Bleeding in cardiac surgery and E-CABG scale. RESULTS: A total of 212 matched pairs (c-statistics 0.693) were selected from patients operated on by residents (n = 294) and specialists (n = 4394) between October 2012 and May 2018. Patients did not differ in bleeding risk. There were no statistically significant differences in postoperative 6-, 12- and 24-h drainages between subjects operated on by residents and specialists, and there was no between-group difference in rethoracotomy or transfusion rate. There were no differences in Universal Definition of Perioperative Bleeding or E-CABG grades. In June 2018, after a median follow-up of 2.8 years (range 0.1-5.7 years), the overall survival was 94%, with no differences between the patients operated on by residents (95%) and specialists (92%) (P = 0.27). CONCLUSIONS: Patients undergoing on-pump CABG, when operated on by a resident, are not exposed to an elevated bleeding risk, as compared with patients operated on by experienced surgeons.
Asunto(s)
Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Internado y Residencia , Hemorragia Posoperatoria/epidemiología , Anciano , Transfusión Sanguínea , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
OBJECTIVES: The aim of the study is to evaluate an optimal way to assess the dimensions of the aortic root and each of the sinuses of Valsalva and examine how a single measurement in 1 plane (echocardiography or 2-dimensional computed tomography) can underestimate the maximum dimension of the aortic root. METHODS: Computed tomography and transthoracic echocardiography images of the aortic root and ascending aorta of 112 patients were analyzed. The minimum and maximum aortic root dimensions, the root perimeter, and the total area of all 3 sinuses of Valsalva were measured on a plane perpendicular to the long axis of the aorta using 3-dimensional multiplanar reconstruction. Moreover, the maximum root dimension was compared with the measurements obtained from the echocardiography and 2-dimensional computed tomography angiography measurements. RESULTS: The difference in the measurements of the minimum and maximum root dimension was 5.4 ± 3.2 mm (range, 0-21 mm, P < .0001) and was significantly larger in patients with bicuspid aortic valves compared with those with tricuspid valves (6.3 ± 4 mm, range, 0-21 mm vs 4.9 ± 2.6 mm, range, 0-15 mm, P = .036). The maximum root dimension measured in 3-dimensional multiplanar reconstruction (49.1 ± 9.0 mm) differed significantly from the root dimension measured in transthoracic echocardiography in the parasternal long-axis view (44.8 ± 8.4 mm) and 2-dimensional computed tomography (axial plane: 45.5 ± 9.0 mm, coronal plane: 46.1 ± 8.8 mm, sagittal plane: 45.1 ± 8.9 mm) (P < .001). CONCLUSIONS: The difference in the measurements of the minimum and maximum aortic root dimensions is significant and may exceed 20 mm, especially in patients with bicuspid aortic valves. Therefore, aortic root dimensions can be significantly underestimated with the measurement (echocardiography, computed tomography angiography) performed in only 1 plane.
Asunto(s)
Aorta , Válvula Aórtica , Ecocardiografía/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Aorta/anatomía & histología , Aorta/diagnóstico por imagen , Válvula Aórtica/anatomía & histología , Válvula Aórtica/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: Left atrial appendage occlusion procedure (LAAO) became an alternative method for stroke prevention in atrial fibrillation (AF) patients with contraindication or intolerance for oral anticoagulation therapy. However, LAA anatomy is complex with several different types of LAA morphology. Therefore matching the correct size of a delivery device to LAA morphology is difficult. In such circumstances, the 3D-printed model of LAA closure may be useful for preoperative planning which increases the efficacy of LAAO procedure. MATERIAL AND METHODS: We report as a first 2 cases of LAA occlusion procedure using 2 different systems: thoracoscopic AtriClip and the LARIAT device in which a 3D printed LAA model was used in preoperative planning. RESULTS: In the first patient, preoperative measurements of 3D LAA model were performed using a dedicated selection guide for AtriClip device were comparable with the intraoperative examination. Left atrial appendage was closed epicardial using 40 mm size AtriClip. In second patients, LAA closure was performed completely percutaneously using LARIAT device. For better visualization of LAA shape on fluoroscopy and TEE examination, intraoperatively sterilized 3D LAA model was used during the procedure. In both cases, intraoperative TEE examination confirmed complete LAA closure with no leak. CONCLUSIONS: Left atrial appendage 3D model is a useful tool in preoperative planning of a left atrial appendage occlusion using epicardial approaches with thoracoscopic or percutaneous access using LARIAT device. The quality of low-cost 3D printed LAA model is sufficient in planning minimally invasive procedure.
RESUMEN
BACKGROUND: Structural valve deterioration (SVD) is a major obstacle to lifetime durability for bioprosthetic heart valves. A bio-prosthetic valve created with RESILIA™ tissue was designed to produce long-term resistance to SVD. AIM: The objective of this study was to evaluate the safety and performance of this new class of RESILIA™ tissue aortic bio-prosthesis. METHODS: A nonrandomised, prospective, multi-centre, single-arm, observational study was performed in 133 patients who underwent surgical aortic valve replacement between July 2011 and February 2013. Patients were assessed at 3-6 months and one year for haemodynamic performance, clinical outcomes, and functional improvement. RESULTS: The mean age was 65.3 ± 13.5 years, with 34 (25.6%) of patients < 60 years of age. Early (≤ 30 day) and late (> 30 day) all-cause mortality rates were 2.3% (n = 3) and 4.5% (n = 6), respectively. Early events included thromboembolism in three (2.3%) patients and major bleeding events requiring transfusion in six (4.5%) patients. Late events included one endocarditis leading to explant. Mean gradients were reduced across all valve sizes and were maintained at one year of follow-up. The mean effective orifice area and effective orifice area index increased across all valve sizes postoperatively and were maintained at one year. The rates of paravalvular leak (> 2+) at 3-6 months and one-year follow-up were 0.7% and 0.7%, respectively. CONCLUSIONS: The new generation RESILIA™ tissue aortic valve bioprosthesis demonstrated excellent haemodynamic per-formance and safety outcomes at one year of follow-up. Longer follow-up of these patients will provide further insight on long-term durability.
Asunto(s)
Válvula Aórtica/cirugía , Bioprótesis , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Seguridad del Paciente , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Valve calcification is well estimated by ex-vivo micro-computed tomography (micro-CT). The objective of this study was to investigate the associations between micro-CT findings and biological indices of calcification in aortic stenosis (AS), as well as differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).MethodsâandâResults:Aortic valves and plasma were obtained from patients undergoing valve surgery. Valves were dissected and underwent micro-CT, genetic analyses, and calcium content assessment. Plasma levels of calcification markers were measured. Forty-two patients with isolated severe AS, including 22 with BAV, were studied. BAV patients had a lower median CT value (140.0 [130.0-152.0] vs. 157.0 [147.0-176.0], P=0.002) and high-density calcification (HDC) fraction (9.3 [5.7-23.3] % vs. 21.3 [14.3-31.2] %, P=0.01), as compared with TAV. Calcification fraction (CF) correlated with AS severity (measured as maximal transvalvular pressure gradient [r=0.34, P=0.03], maximal flow velocity [r=0.38, P=0.02], and indexed aortic valve area [r=-0.37, P=0.02]). For TAV patients only, mRNA expression of integrin-binding sialoprotein correlated with CF (r=0.45, P=0.048), and the receptor activator of the nuclear factor κ-B ligand transcript correlated with HDC corrugation (r=0.54, P=0.01). CONCLUSIONS: TAV patients with AS present more mineralized calcifications in micro-CT than BAV subjects. The relative volume of calcifications increases with the AS severity. In TAV patients, upregulated expression of genes involved in osteoblastogenesis in AS correlates with leaflet mineralization in micro-CT.
Asunto(s)
Estenosis de la Válvula Aórtica , Sialoproteína de Unión a Integrina/biosíntesis , Válvula Mitral , Ligando RANK/biosíntesis , Válvula Tricúspide , Calcificación Vascular , Microtomografía por Rayos X , Anciano , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/metabolismo , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/metabolismo , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/metabolismoRESUMEN
Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PAD chemotherapy (bortezomib, doxorubicin and dexamethasone). Comparative proteomic analysis was conducted on pretreatment plasma cells from 77 proteasome inhibitor naïve patients treated subsequently with PAD due to RRMM. To increase data confidence we used two independent proteomic platforms: isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and label free (LF). Proteins were considered as differentially expressed when their accumulation between groups differed by at least 50% in iTRAQ and LF. The proteomic signature revealed 118 proteins (35 up-regulated and 83 down-regulated in ≥ VGPR group). Proteins were classified into four classes: (1) involved in proteasome function; (2) involved in the response to oxidative stress; (3) related to defense response; and (4) regulating the apoptotic process. We confirmed the differential expression of proteasome activator complex subunit 1 (PSME1) by enzyme-linked immunosorbent assay. Increased expression of proteasomes and proteins involved in protection from oxidative stress (eg., TXN, TXNDC5) plays a major role in bortezomib resistance.