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BACKGROUND AND AIMS: Adenosine is a widely used potent cardioprotective drug, but the effect of an adenosine bolus in initial cardioplegia on cardioprotection in aortic valve replacement (AVR) patients has not been demonstrated. The aim of this double-blind randomized clinical trial was to compare intra-aortic adenosine bolus with saline on the postoperative myocardial function in patients undergoing AVR. METHODS: Aortic valve stenosis patients scheduled for elective or urgent AVR surgery were randomized to receive either a 20 mg (4 mL) single dose of adenosine or a saline into the ascending aorta during the first cardioplegia infusion. The primary outcome was cardiac index (CI (L/min/m2) at four timepoints (before incision, after weaning from cardiopulmonary bypass (CPB), at 7 p.m. on the operation day, and at 6 a.m. the next morning). Secondary outcomes included left ventricular stroke work index, right ventricular stroke work index, and myocardial biomarkers at the same timepoints. RESULTS: Between November 2015 and March 2018, 45 patients were recruited, 23 in the adenosine group and 22 in the placebo group. The last follow-up date was 17 March 2018. There were no statistically significant differences in CI (mean differences with 95% confidence interval (95% CI): 0.09 L/min/m2 at baseline (-0.20 to 0.38), -1.39 L/min/m2 (-3.47 to 0.70) at post-CPB, -0.39 L/min/m2 (-0.78 to 0.004) at 7 p.m., and -0.32 L/min/m2 (-0.68 to 0.05) at 6 a.m., (p = 0.066)), right ventricular stroke work index, (p = 0.24), or cardiac biomarkers between the groups. Left ventricular stroke work index was lower in the adenosine group (-3.66 gm/m2 (-11.13 to 3.81) at baseline, -17.42 gm/m2 (-37.81 to 2.98) at post-CPB, -3.36 gm/m2 (-11.10 to 4.38) at 7 p.m., and -3.77 gm/m2 (-10.19 to 2.66) at 6 a.m. (p = 0.021)). CONCLUSIONS: There were no differences between 20 mg adenosine bolus and saline in the first cardioplegia infusion in CI improvement in AVR surgery for aortic valve stenosis.EudraCT number: 2014-001382-26.
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BACKGROUND: The incidence of pleural infections appears to be increasing in Western countries for unclear reasons. The aim of the study was to describe the incidence and treatment patterns of pleural infections in Finland over three decades. METHODS: Data regarding each treatment episode for pleural infections in the Finnish special medical care between January 1994 and December 2016 was obtained from a national database and compared to the demographics of Finnish residents obtained from the national census bureau. The annual incidence rates, type of treatment given, as well as the lengths of the hospitalization were analyzed. RESULTS: A total of 28,463 episodes were reported, of which 55% were inpatient episodes. Of these, 76% concerned males, and the median age of patients was 60 (interquartile range 49-70) years. The overall incidence of pleural infections was 23.4 per 100.000 patient-years, with a male-to-female -ratio of 3.3:1. The annual incidence rates increased throughout the study period with an average annual percentage change of +11.4% (95% CI ±7.4%). The highest incidence rates (>200 per 100.000 patient-years) were observed in men aged 80 or more. Altogether 88% of patients were treated conservatively. The proportion of patients treated by mini-invasive surgery significantly increased during study period (0-5.9%, p < 0.001) and was associated with shorter hospitalization (median 6 [interquartile range 4-12] days) than open surgery (median 7 [4.5-13] days) (p < 0.001). CONCLUSION: The incidence of pleural infections has increased significantly over the previous decades in Finland and appears to be higher than previously reported, particularly in elderly men.
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Background: The incidence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), after lung cancer resections varies in the literature, and there is limited evidence regarding the optimal duration of thromboprophylaxis. This study aimed at determining the early and long-term occurrence of thromboembolic complications in patients who received in-hospital thromboprophylaxis and underwent resective surgery for lung cancer. Methods: The study included all patients who underwent lung cancer surgery at Tampere University Hospital between 2004 and 2016. Postoperative thromboprophylaxis was administered for the duration of the hospitalization. Data on subsequent episodes of VTE and survival were obtained from national registries. The results were compared to a demographically matched reference population. Results: The study comprised 435 patients and 4,338 individuals in the reference population. The overall occurrence of VTE in patients and the reference group was 0.3% vs. 0.2% at 90 days (P=0.56), 3.5% vs. 0.7% at 1 year (P<0.001), 9.2% vs. 2.2% at 3 years (P<0.001), and 18.7% and 3.9% at 5 years (P<0.001), respectively. The majority of cases represented PE. The overall mortality at 5 years was 44.4% vs. 11.6% (P<0.001). No associations between patient characteristics and the occurrence of VTE during follow-up were detected. Conclusions: Patients undergoing lung cancer surgery and who receive in-hospital medical thromboprophylaxis do not seem to be in high risk for symptomatic VTE during the early postoperative period. However, during long-term follow-up the occurrence of symptomatic VTE was significant.
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BACKGROUND AND OBJECTIVE: As markers of sarcopenia, psoas muscle areas and indexes measured from computed tomography images have been found to predict long-term mortality in cardiothoracic as well as other surgical cohorts. Our objective was to investigate the association between psoas muscle status, taking into account muscle density in addition to area, and survival among patients undergoing open thoracic aortic reconstruction. METHODS: This was a retrospective registry study of a total of 451 patients treated with open surgery for thoracic aortic pathology. Psoas muscle area and density were measured from preoperative computed tomography images at the L3 and L4 lumbar levels. In addition, lean psoas muscle area was calculated by averaging sex-specific values of psoas muscle area and density. The association between mortality and psoas muscle status was analyzed with adjusted Cox-regression analysis. RESULTS: The median age of the study population was 63 (interquartile range (IQR): 53-70) years. The majority were male (74.7%, n = 337) and underwent elective procedures (58.1% n = 262). Surgery of the ascending aorta was carried out in 90% of the patients, and 15% (n = 67) had concomitant coronary artery bypass surgery. Aortic dissection was present in 34.6% (n = 156) patients. Median follow-up time was 4.3 years (IQR: 2.2-7.4). During the follow-up, 106 patients (23.5%) died, with 55.7% of deaths occurring within the first four postoperative weeks. Psoas muscle parameters were not associated with perioperative mortality, but significant independent associations with long-term mortality were observed for psoas muscle area, density, and lean psoas muscle area with hazard ratios (HRs) of 0.63 (95% confidence interval (CI): 0.45-0.88), 0.62 (95% CI: 0.46-0.83), and 0.47 (95% CI: 0.32-0.69), respectively (all per 1-SD increase). CONCLUSIONS: Psoas muscle sarcopenia status is associated with long-term mortality after open thoracic aortic surgery.
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OBJECTIVES: The purpose of this study was to detect changes in QoL after coronary artery bypass grafting surgeries (CABG) in one year, and to identify the possible predictive factors associated with the change. DESIGN: A single-center prospective study of 501 patients was conducted between 2013 and 2018 using the EQ-5D VAS questionnaire for estimating the QoL. The patients filled in a questionnaire preoperatively, at 6 and at 12 months postoperatively. Univariate and multivariable logistic regression analyses were used to find out if certain pre-selected factors or EQ5D dimensions had independent effects on the observed EQ VAS scores. RESULTS: QoL improved in all EQ-5D dimensions and in EQ VAS scores at 6 and at 12 months: the greatest changes in the number of reported problems were in the dimensions "mobility" (-34.2%, p<.001), "self-care" (-36.7%, p=.001) and "pain or discomfort" (-31.0%, p<.001). With the multivariable regression model, we could show that normal left ventricle ejection fraction (LVEF) and improvement in mobility and pain/discomfort dimensions were in association with improvement of EQ VAS score at 6 months. At 12 months this association was no longer detectable. CONCLUSIONS: CABG procedure can improve patient's QoL when judged with EQ5D dimensions and related overall self-rated health (VAS). This improvement was seen both at 6 and at 12 months postoperatively. Except for LVEF, the other patient-specific risk factors we examined did not seem to affect QoL in the long term.
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Puente de Arteria Coronaria , Calidad de Vida , Humanos , Estudios de Seguimiento , Estudios Prospectivos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Encuestas y Cuestionarios , DolorRESUMEN
RESULTS: In the meta-analysis, psoas muscle measurements were significantly associated with mortality among men (p < 0.05), with high heterogeneity in the associations across all cohorts. There was very little difference in the association between PMA and PMD and mortality (HR 0.83, 95% CI 0.69-0.99, p = 0.002; HR 0.85, 95% CI 0.77-0.94, p = 0.041 for one SD increase in PMA and PMD in the random effects model). Combining PMA and PMD into one composite variable by multiplying their values together showed the most robust association in terms of the magnitude of the effect size in men (HR, 0.77; 95% CI 0.73-0.87, p < 0.001). Indexing PMA to body size did not result in any significant differences in this association. Among women, psoas muscle measurements were not associated with long-term mortality in this meta-analysis. CONCLUSIONS: Different psoas muscle measurements were significantly and very similarly associated with mortality among men but not among women. No single measurement stands out, although combining PMA and PMD seems to be a slightly stronger estimate in terms of effect size and should be considered in further studies.
Significant sarcopenia affecting survival in patients undergoing heavy invasive operations may be preoperatively assessed using images of psoas muscle (PM) from routine computerized tomography but the optimal method for evaluation is unclear. A meta-analysis of individual participant data of over two thousand patients undergoing cardiovascular interventions shows that different PM measurements of surface area and density were significantly and very similarly associated with mortality among men but not among women. Combining PM area with PM density to one estimate of lean psoas muscle area seems to provide the strongest hazard estimate among men.
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Músculos , Músculos Psoas , Masculino , Femenino , HumanosRESUMEN
BACKGROUND AND AIMS: A deep sternal wound infection is a life-threatening complication after cardiac surgery. This study was conducted to describe the mortality associated with postoperative deep sternal wound infections after cardiac surgery and to find risk factors linked to increased mortality in 1 year follow-up. MATERIAL AND METHODS: A total of 7973 open-heart surgeries were performed at Tampere University Hospital. Deep sternal wound infection patients were identified, their 1-year mortality status was recorded, and the related risk factors were analyzed. RESULTS: We detected a total of 129 (1.6%) postoperative deep sternal wound infection patients. The 1-year mortality associated with a postoperative deep sternal wound infection was 20.2%. No preoperative or perioperative, statistically significant factors associated with increased 1-year mortality were found. A prolonged stay in an intensive care unit after surgery as well as stroke, delirium, wound secretion, and co-infection were associated with increased 1-year mortality. CONCLUSION: The risk factors found for increased 1-year mortality were all postoperative. The quality of surgical treatment as well as precise postoperative care and evaluation remain the most important factors to decrease later mortality due to deep sternal wound infections.
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Procedimientos Quirúrgicos Cardíacos , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Factores de Riesgo , Esternón/cirugía , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Estudios RetrospectivosRESUMEN
The aim of the present study was to investigate the levels of YKL-40 during and after coronary artery bypass grafting surgery (CABG) and to establish possible connections between YKL-40 and markers of oxidative stress, inflammation, and myocardial injury. Patients undergoing elective CABG utilizing cardiopulmonary bypass (CPB) were recruited into the study. Blood samples were collected at the onset of anesthesia, during surgery and post-operatively. Levels of YKL-40, 8-isoprostane, interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and troponin T (TnT) were measured by immunoassay. YKL-40 levels increased significantly 24 h after CPB. Positive correlation was seen between post-operative TnT and YKL-40 levels (r = 0.457, p = 0.016) and, interestingly, baseline YKL-40 predicted post-operative TnT increase (r = 0.374, p = 0.050). There was also a clear association between YKL-40 and the chemotactic factors MCP-1 (r = 0.440, p = 0.028) and IL-8 (r = 0.484, p = 0.011) linking YKL-40 to cardiac inflammation and fibrosis following CABG. The present results show, for the first time, that YKL-40 is associated with myocardial injury and leukocyte-activating factors following coronary artery bypass surgery. YKL-40 may be a factor and/or biomarker of myocardial inflammation and injury and subsequent fibrosis following heart surgery.
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Quimiotaxis de Leucocito , Proteína 1 Similar a Quitinasa-3 , Lesiones Cardíacas , Humanos , Biomarcadores , Quimiotaxis de Leucocito/genética , Quimiotaxis de Leucocito/fisiología , Proteína 1 Similar a Quitinasa-3/metabolismo , Puente de Arteria Coronaria/efectos adversos , Fibrosis , Glicoproteínas , Lesiones Cardíacas/genética , Lesiones Cardíacas/metabolismo , Inflamación , Interleucina-8 , Proyectos PilotoRESUMEN
BACKGROUND AND OBJECTIVE: In this clinical trial, we evaluated if a short-acting nucleoside, adenosine, as a high-dose bolus injection with blood cardioplegia induces faster arrest and provides better myocardial performance in patients after bypass surgery for coronary artery disease. METHODS: Forty-three patients scheduled for elective or urgent coronary artery bypass grafting were prospectively recruited in two-arm 1:1 randomized parallel groups to either receive 20 mg of adenosine (in 21 patients) or saline (in 22 patients) into the aortic root during the first potassium-enriched blood cardioplegia infusion. The main outcomes of the study were ventricular myocardial performance measured with cardiac index, right ventricular stroke work index, and left ventricular stroke work index at predefined time points and time to asystole after a single bolus injection of adenosine. Conventional myocardial biomarkers were compared between the two groups at predefined time points as secondary endpoints. Electrocardiographic data and other ad hoc clinical outcomes were compared between the groups. RESULTS: Compared with saline, adenosine reduced the time to asystole (68 (95% confidence interval (95% CI) = 37-100) versus 150 (95% CI = 100-210) seconds, p = 0.005). With myocardial performance, the results were inconclusive, since right ventricular stroke work index recovered better in the adenosine group (p = 0.008), but there were no significant overall differences in cardiac index and left ventricular stroke work index between the groups. Only the post-cardiopulmonary bypass cardiac index was better in the adenosine group (2.3 (95% CI = 2.2-2.5) versus 2.1 (95% CI = 1.9-2.2) L/min/m2, p = 0.016). There were no significant differences between the groups in cardiac biomarker values. CONCLUSIONS: A high dose adenosine bolus at the beginning of the first cardioplegia infusion resulted in significantly faster asystole in coronary artery bypass grafting patients but enhanced only partially the ventricular performance.EudraCT number: 2014-001382-26. https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001382-26/FI.
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Paro Cardíaco , Accidente Cerebrovascular , Adenosina/uso terapéutico , Puente de Arteria Coronaria/métodos , Estudios de Factibilidad , Paro Cardíaco Inducido/métodos , Humanos , Nucleósidos , PotasioRESUMEN
BACKGROUND: The disease course of idiopathic pulmonary fibrosis (IPF) is progressive and occasionally, other types of interstitial lung disease (ILD) may progress similarly to IPF. This study aimed to evaluate risk factors for disease progression within 24 months in patients with various ILDs. METHODS: This prospective study obtained 97 patients with a suspected ILD who underwent a transbronchial lung cryobiopsy. The extent of several high-resolution computed tomography (HRCT) patterns was assessed. Due to the inclusion criteria the study population presented a low extent of honeycombing and definite usual interstitial pneumonia (UIP) pattern on HRCT suggesting an early stage of ILD. Disease progression within 24 months despite treatment was defined as a relative decline of ≥ 10% in forced vital capacity (FVC), or a relative decline in FVC of ≥ 5% and one of the three additional criteria: (1) a decline in diffusion capacity to carbon monoxide (DLCO) ≥ 15%; (2) increased fibrosis on HRCT; (3) progressive symptoms, or progressive symptoms and increased fibrosis on HRCT. The same definition was utilized in patients with IPF and other ILDs. Risk factors for disease progression were evaluated in a multivariable logistic regression model. RESULTS: Disease progression was revealed in 52% of the patients with ILD, 51% of the patients with IPF, and 53% of the patients with other types of ILD. A high extent of reticulation on HRCT (Odds ratio [OR] 3.11, 95% Confidence interval [CI] 1.21-7.98, P = 0.019) and never smoking (OR 3.11, CI 1.12-8.63, P = 0.029) were associated with disease progression whereas platelet count (OR 2.06 per 100 units increase, CI 0.96-4.45, P = 0.065) did not quite reach statistical significance. CONCLUSION: Higher extent of reticulation on HRCT and never smoking appeared to associate with the risk of disease progression within 24 months in ILD patients without honeycombing. Approximately half of the patients with ILD revealed disease progression, and similar proportions were observed in patients with IPF and in other types of ILD.
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Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Progresión de la Enfermedad , Fibrosis , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.
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BACKGROUND: The use of a transbronchial lung cryobiopsy (TBLC) is increasing as a diagnostic method of interstitial lung diseases (ILD). This study aimed to evaluate risk factors associated with clinically significant complications of TBLC in ILD patients. METHODS: Patients referred to Kuopio or Tampere university hospitals, in Finland, for a suspected ILD were included. The TBLC was performed in an outpatient setting for 100 patients. Patients were mechanically ventilated in general anesthesia. Fluoroscopy guidance and prophylactic bronchial balloon were used. Complications, such as bleeding, pneumothorax, infections, and mortality were recorded. Moderate or serious bleeding, pneumothorax, or death ≤90 days were defined as clinically significant complications. A multivariable model was created to assess clinically significant complications. RESULTS: The extent of traction bronchiectasis (Odds ratio [OR] 1.30, Confidence interval [CI] 1.03-1.65, p = 0.027) and young age (OR 7.96, CI 2.32-27.3, p = 0.001) were associated with the risk of clinically significant complications whereas the use of oral corticosteroids ≤30 days before the TBLC (OR 3.65, CI 0.911-14.6, p = 0.068) did not quite reach statistical significance. A history of serious cough was associated with the risk of pneumothorax (OR 4.18, CI 1.10-16.0, p = 0.036). Procedure associated mortality ≤90 days was 1%. CONCLUSION: The extent of traction bronchiectasis on HRCT and young age were associated with the risk of clinically significant complications whereas oral corticosteroid use did not quite reach statistical significance. A history of serious cough was associated with the risk of clinically significant pneumothorax.
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Bronquiectasia , Enfermedades Pulmonares Intersticiales , Neumotórax , Biopsia/métodos , Bronquiectasia/etiología , Broncoscopía/efectos adversos , Broncoscopía/métodos , Tos/etiología , Humanos , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico , Neumotórax/epidemiología , Neumotórax/etiología , Neumotórax/patología , Estudios Prospectivos , Factores de RiesgoRESUMEN
Objectives. Quality of life (QoL) is possibly the most important variable for the patient when subjective results of heart procedures are evaluated. The purpose of this study was to analyze the change in the quality of life 1 year after surgical aortic valve replacement (SAVR). Design. A Finnish single-center prospective cohort intervention study was performed from 2013 to 2018. QoL was assessed with the EQ-5D-3L VAS questionnaire before surgery and 6 and 12 months after surgery. We used univariate analysis to assess the change in the number of people experiencing problems and logistic regression analysis to assess the patients' characteristics on the change in QoL. Results. At one year follow-up, patients' quality of life improved in all EQ-5D dimensions. The greatest decreases in patients experiencing problems 12 months after surgery occurred in the dimension "mobility" (-24.1% change in reporting problems, p < .01), "self-care" (-32.9%, p < .01), and "pain or discomfort" (-25.7%, p < .01). Before surgery mean of EQ visual analogue scale (VAS, from 0 to 100) was 63.0 (SD 17.7, n = 604), and 12 months after surgery 81.2 (SD 13.8, n = 367, p < .001). In multivariable analysis, preoperative obesity was associated with better quality of life (OR 3.39, 95% CI 1.007-11.439) in "daily activities" and patients' higher operative risk was associated with better "self-care" after surgery. Conclusions. SAVR can improve the 1-year quality of life in all dimensions of EQ-5D and self-rated overall health (VAS).
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Válvula Aórtica , Calidad de Vida , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Humanos , Dimensión del Dolor/métodos , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
INTRODUCTION: There are several potential causes of QRS-axis deviation in the ECG, but there is limited data on the prognostic significance of QRS-axis deviation in ACS patients. SUBJECTS AND METHODS: We evaluated the long-term prognostic significance of acute phase frontal plane QRS-axis deviation and its shift during hospital stay in ACS patients. A total of 1026 patients who met the inclusion criteria were divided into three categories: normal (n = 823), left (n = 166) and right/extreme axis (n = 37). RESULTS: The median survival time was 9.0 years (95% CI 7.9-10.0) in the normal, 3.6 years (95% CI 2.4-4.7) in the left and 1.3 years (95% CI 0.2-2.4) in the right/extreme axis category. Both short and long-term all-cause mortality was lowest in the normal axis category and highest in the right/extreme axis category. Compared to normal axis, both admission phase QRS-axis deviation groups were independently associated with a higher risk of all-cause mortality. When including left ventricular hypertrophy in the ECG, only the right/extreme axis retained its statistical significance (aHR 1.76; 95% CI 1.16-2.66, p = 0.007). Axis shift to another axis category had no effect on mortality. CONCLUSION: In ACS patients, acute phase QRS-axis deviation was associated with higher risk of all-cause mortality. Among the axis deviation groups, right/extreme QRS-axis deviation was the strongest predictor of mortality in the multivariable analysis. Further studies are required to investigate to what extent this association is caused by pre-existing or by ACS-induced axis deviations. QRS-axis shift during hospital stay had no effect on all-cause mortality.
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Síndrome Coronario Agudo , Síndrome Coronario Agudo/diagnóstico , Arritmias Cardíacas , Electrocardiografía , Humanos , Hipertrofia Ventricular Izquierda , PronósticoRESUMEN
Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes. Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell-cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery. Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.
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BACKGROUND: Two respiratory physiotherapy modalities were compared in a randomized controlled trial on patients undergoing minor pleuro-pulmonary surgery. METHODS: Forty-five patients were randomly allocated into positive expiratory pressure (PEP) therapy (n=23) and inspiratory muscle training (IMT) groups (n=22). Individualized group specific physiotherapeutic guidance was administered preoperatively, and once a day postoperatively. Patients also performed independent exercises and kept a logbook. Pain was assessed on a numerical reference scale (NRS). Volumetric pulmonary function values and walking distance were recorded preoperatively, and on first (POD1) and second postoperative days (POD2). Pre- and postoperative values were compared using two-way repeated measures analysis of variance. RESULTS: Patient characteristics and pleuro-pulmonary interventions were similar between the groups. Thoracotomy was performed in 14/45 and video assisted surgery (VATS) in 31/45 of cases. Preoperative volumetric pulmonary functions were normal or slightly decreased in 29/45, and fell significantly (P<0.001) on the first postoperative day (POD1) and improved but remained significantly lower on the second postoperative day. The recovery of mean FEV1, FIV1 and FIVC values was greater in the IMT than in the PEP group between POD1 and POD2, but without significant difference. The corresponding relative to preoperative values were higher in the IMT group, with a significant difference in FEV1 (P=0.045). Also relative PEF and FIV1 values seemed to be slightly higher in the IMT compared to the PEP group, but not significantly. Average NRS values for pain were lower in the IMT group (P=0.010) but only on POD1. Air leak was noted in 4/45 patients, two in each group, on POD1, and two in PEP groups and one in IMT group on POD2. Mean measured walking distances between groups did not differ. Mean hospital stay was 4 days in the PEP group and 3 days in the IMT group. There was no hospital mortality. CONCLUSIONS: Pulmonary function values decreased significantly after minor lung resections, supporting rehabilitative respiratory physiotherapy to avoid postoperative pulmonary complications (PPCs). Both PEP and IMT training were well tolerated and equally efficient when comparing spirometry values at three time points. IMT appeared advantageous regarding relative FEV1 recovery and immediate postoperative pain.
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Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.
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Epigénesis Genética , Epigenómica/métodos , Isquemia Miocárdica/metabolismo , ARN/metabolismo , Transcriptoma , Biomarcadores , Estudios de Casos y Controles , Humanos , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Despite the steady improvements in survival and operative safety, postoperative complications still remain a significant cause of morbidity and mortality after coronary artery bypass grafting (CABG). However, less is known on the impact of postoperative complications on health-related quality of life (QoL). The main objective of our study was to investigate the impact of postoperative complications on long-term QoL and survival after CABG surgery. METHODS: Data of 508 patients, who underwent isolated CABG was prospectively collected. The RAND-36 Health Survey (RAND-36) was used to evaluate patients' QoL status preoperatively, 1 year and 12 years after the surgery. Predefined postoperative complications were reported during primary and secondary hospital stay. QoL and survival analysis were performed primarily on three patient groups: patients with and without complications and patients with major adverse cardiac and cerebrovascular events (MACCE). RESULTS: In total 205(40%) of 508 patients had at least one postoperative complication and 73 (14%) experienced MACCE. Patients' thirty-day, 1-year and 10-year survival rates were, 99, 98, 84% without complications, 97, 95, 72% with complications, and 90, 89, 64% with MACCE, respectively (log-rank p < 0.001). Patients without complications showed significant(p < 0.05) improvements in seven and patients with complications in five out of eight RAND-36 QoL dimensions. All patient groups showed significant improvements in RAND-36 summary scores compared with preoperative values. Patients with complications and especially with MACCE had more profound decline in their RAND-36 summary scores while patients without complications maintained their health status best. CONCLUSIONS: Despite the constant deterioration, both patients with and without complications showed improvements even 12 years after CABG compared with preoperative state. Postoperative complications and especially MACCE were associated with impaired long-term QoL.
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Puente de Arteria Coronaria/efectos adversos , Complicaciones Posoperatorias , Calidad de Vida , Anciano , Trastornos Cerebrovasculares/etiología , Cardiopatías/etiología , Cardiopatías/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios ProspectivosRESUMEN
INTRODUCTION: Atrial fibrillation (AF) is a frequent finding in acute coronary syndrome (ACS), but there is conflicting scientific evidence regarding its long-term impact on patient outcome. The aim of this study was to survey and compare the ≥10-year mortality of ACS patients with sinus rhythm (SR) and AF. METHODS: Patients were divided into 2 groups based on rhythm in their 12-lead ECGs: (1) SR (n = 788) at hospital admission and discharge (including sinus bradycardia, physiological sinus arrhythmia, and sinus tachycardia) and (2) AF/atrial flutter (n = 245) at both hospital admission and discharge, or SR and AF combination. Patients who failed to match the inclusion criteria were excluded from the final analysis. The main outcome surveyed was long-term all-cause mortality between AF and SR groups during the whole follow-up time. RESULTS: Consecutive ACS patients (n = 1,188, median age 73 years, male/female 58/42%) were included and followed up for ≥10 years. AF patients were older (median age 77 vs. 71 years, p < 0.001) and more often female than SR patients. AF patients more often presented with non-ST-elevation myocardial infarction (69.8 vs. 50.4%, p < 0.001), had a higher rate of diabetes (31.0 vs. 22.8%, p = 0.009), and were more often using warfarin (32.2 vs. 5.1%, p < 0.001) or diuretic medication (55.1 vs. 25.8%, p < 0.001) on admission than patients with SR. The use of warfarin at discharge was also more frequent in the AF group (55.5 vs. 14.8%, p < 0.001). The rates of all-cause and cardiovascular mortality were higher in the AF group (80.9 vs. 50.3%, p < 0.001, and 73.8 vs. 69.6%, p = 0.285, respectively). In multivariable analysis, AF was independently associated with higher mortality when compared to SR (adjusted HR 1.662; 95% CI: 1.387-1.992, p < 0.001). CONCLUSION: AF/atrial flutter at admission and/or discharge independently predicted poorer long-term outcome in ACS patients, with 66% higher mortality within the ≥10-year follow-up time when compared to patients with SR.
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Síndrome Coronario Agudo , Fibrilación Atrial , Aleteo Atrial , Síndrome Coronario Agudo/complicaciones , Anciano , Fibrilación Atrial/complicaciones , Electrocardiografía , Femenino , Hospitalización , Humanos , Masculino , Resultado del TratamientoRESUMEN
AIMS: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. METHODS AND RESULTS: We carried out a genome-wide association study for MI in the UK Biobank (nâ¼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (nâ¼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (nâ¼165 000) and 16 independent angiography-based cohorts (nâ¼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1ß (vs. vehicle), and associated with smooth muscle cell migration in vitro. CONCLUSIONS: A large-scale analysis comprising â¼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.