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Chronic kidney disease (CKD) is associated with elevated plasma fibrinogen concentration. However, the underlying molecular mechanism for elevated plasma fibrinogen concentration in CKD patients has not yet been clarified. We recently found that HNF1α was significantly upregulated in the liver of chronic renal failure (CRF) rats, an experimental model of CKD in patients. Given that the promoter region of the fibrinogen gene possesses potential binding sites for HNF1α, we hypothesized that the upregulation of HNF1α can increase fibrinogen gene expression and consequently plasma fibrinogen concentration in the experimental model of CKD. Here, we found the coordinated upregulation of Aα-chain fibrinogen and Hnfα gene expression in the liver and elevated plasma fibrinogen concentrations in CRF rats, compared with pair-fed and control animals. Liver Aα-chain fibrinogen and HNF1α mRNAs levels correlated positively with (a) liver and plasma fibrinogen levels and (b) liver HNF1α protein levels. The positive correlation between (a) liver Aα-chain fibrinogen mRNA level, (b) liver Aα-chain fibrinogen level, and (c) serum markers of renal function suggest that fibrinogen gene transcription is closely related to the progression of kidney disease. Knockdown of Hnfα in the HepG2 cell line by small interfering RNA (siRNA) led to a decrease in fibrinogen mRNA levels. Clofibrate, an anti-lipidemic drug that reduces plasma fibrinogen concentration in humans, decreased both HNF1α and Aα-chain fibrinogen mRNAs levels in (a) the liver of CRF rats and (b) HepG2 cells. The obtained results suggest that (a) an elevated level of liver HNF1α can play an important role in the upregulation of fibrinogen gene expression in the liver of CRF rats, leading to an elevated concentration of plasma fibrinogen, a protein related to the risk of cardiovascular disease in CKD patients, and (b) fibrates can decrease plasma fibrinogen concentration through inhibition of HNF1α gene expression.
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Fibrinogênio , Falência Renal Crônica , Ratos , Humanos , Animais , Fibrinogênio/genética , Fibrinogênio/metabolismo , Fígado/metabolismo , Falência Renal Crônica/genética , Falência Renal Crônica/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/metabolismo , Expressão Gênica , Fatores Nucleares de Hepatócito/genética , Fatores Nucleares de Hepatócito/metabolismoRESUMO
Chronic kidney disease (CKD) is associated with low-grade inflammation that activates nuclear factor-κB (NF-κB), which upregulates the expression of numerous NF-κB responsive genes, including the genes encoding IL-6, ICAM-1, VCAM-1, and MCP-1. Herein, we found the coordinated overexpression of genes encoding RelA/p65 (a subunit of NF-κB) and HNF1α in the livers of chronic renal failure (CRF) rats-an experimental model of CKD. The coordinated overexpression of RelA/p65 and HNF1α was associated with a significant increase in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. A positive correlation between liver RelA/p65 mRNA levels and a serum concentration of creatinine and BUN suggest that RelA/p65 gene transcription is tightly related to the progression of renal failure. The knockdown of HNF1α in the HepG2 cell line by siRNA led to a decrease in Rel A/p65 mRNA levels. This was associated with a decrease in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. The simultaneous repression of HNF-1α and RelA/p65 by clofibrate is tightly associated with the downregulation of IL-6, ICAM-1, VCAM-1, and MCP-1 gene expression. In conclusion, our findings suggest that NF-κB could be a downstream component of the HNF1α-initiated signaling pathway in the livers of CRF rats.
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NF-kappa B , Insuficiência Renal Crônica , Animais , Linhagem Celular Tumoral , Fator 1-alfa Nuclear de Hepatócito , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/genética , Fígado/metabolismo , Modelos Teóricos , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Ratos , Insuficiência Renal Crônica/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Inflammation related to chronic kidney disease (CKD) is an important clinical problem. We recently determined that hepatocyte nuclear factor 1α (HNF1α) was upregulated in the livers of chronic renal failure (CRF) rats-experimental model of CKD. Considering that the promoter region of gene encoding C-reactive protein (CRP) contains binding sites for HNF1α and that the loss-of-function mutation in the Hnfs1α leads to significant reduction in circulating CRP levels, we hypothesized that HNF1α can activate the Crp in CRF rats. Here, we found coordinated upregulation of genes encoding CRP, interleukin-6 (IL-6), HNF1α, and HNF4α in the livers and white adipose tissue (WAT) of CRF rats, as compared to the pair-fed and control animals. This was accompanied by elevated serum levels of CRP and IL-6. CRP and HNFs' mRNA levels correlated positively with CRP and HNFs' protein levels in the liver and WAT. Similar upregulation of the Crp, Il-6, and Hnfs in the liver and WAT and increased serum CRP and IL-6 concentrations were found in lipopolysaccharide (LPS)-induced systemic inflammation in rats. Moreover, silencing HNF1α in HepG2 cells by small interfering RNA led to decrease in CRP mRNA levels. Our results suggests that (a) HNFs act in concert with IL-6 in the upregulation of CRP production by the liver and WAT, leading to an increase in circulating CRP concentration in CRF rats and (b) CRF-related inflammation plays an important role in the upregulation of genes that encode HNFs and CRP in the liver and WAT of CRF rats.
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Tecido Adiposo Branco/metabolismo , Proteína C-Reativa/biossíntese , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Falência Renal Crônica/metabolismo , Fígado/metabolismo , Transcrição Gênica , Regulação para Cima , Tecido Adiposo Branco/patologia , Animais , Proteína C-Reativa/genética , Modelos Animais de Doenças , Células Hep G2 , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/genética , Humanos , Interleucina-6/biossíntese , Interleucina-6/genética , Falência Renal Crônica/genética , Falência Renal Crônica/patologia , Fígado/patologia , Masculino , Ratos , Ratos WistarRESUMO
Dyslipidemia commonly present in patients with chronic kidney disease (CKD) has been recently linked to increased proprotein convertase subtilisin/kexin type 9 (PCSK9) serum concentration. We tested a hypothesis that increased liver PCSK9 biosynthesis could be partially responsible for the elevated circulating PCSK9 level, and subsequently contribute to hypercholesterolemia observed in subjects with CKD. Rat model of chronic renal failure (CRF) was used in the study. Animals underwent a 5/6 nephrectomy or a sham operation. Liver expression of Pcsk9, sterol regulatory element-binding transcription factor 2 (Srebf-2), and ß-actin were quantified by real-time RT-PCR. Liver protein levels of PCSK9, LDL-receptor (LDL-R), and SREBF-2 were analyzed using Western blotting. Serum PCSK9 concentration was estimated by immunoassay. Rats with an experimental CRF as compared to pair-fed and control ones were characterized by: (a) an up-regulation of liver Pcsk9 and Srebf-2 genes expression with parallel increase of serum PCSK9 concentration; (b) a decrease in liver LDL-R protein level, and (c) an increase of serum total and LDL-cholesterol concentrations. We also found significant correlations between serum creatinine and liver PCSK9 mRNA levels (r = 0.88, p < 0.001) and between serum creatinine and circulating PCSK9 levels (r = 0.73, p < 0.001). The results suggest that a rat model of CRF is associated with an increased liver Pcsk9 gene expression. The coordinated up-regulation of Pcsk9 and Srebf-2 genes expression suggests that SREBF-2 may play a key role in regulation of Pcsk9 gene expression, circulating PCSK9 level, and hypercholesterolemia in experimental CRF.
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Hipercolesterolemia/genética , Fígado/enzimologia , Serina Endopeptidases/genética , Regulação para Cima , Animais , Masculino , Pró-Proteína Convertase 9 , RNA Mensageiro/genética , Ratos , Ratos Wistar , Serina Endopeptidases/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismoRESUMO
Chemerin is an adipokine modulating inflammatory response and affecting glucose and lipid metabolism. These disturbances are common in CKD. The aim of the study was: (a) to evaluate circulating chemerin level at different stages of CKD; (b) to measure subcutaneous adipose tissue chemerin gene expression; (c) to estimate the efficiency of renal replacement therapy in serum chemerin removal. 187 patients were included into the study: a) 58 patients with CKD; (b) 29 patients on hemodialysis; (c) 20 patients after kidney transplantation. 80 subjects constituted control group. Serum chemerin concentration was estimated by ELISA. The adipose tissue chemerin mRNA level was measured by RT-qPCR. The mean serum chemerin concentration in CKD patients was 70% higher than in the control group (122.9 ± 33.7 vs. 72.6 ± 20.7 ng/mL; p < 0.001) and it negatively correlated with eGFR (r = -0.71, p < 0.001). The equally high plasma chemerin level was found in HD patients and a HD session decreased it markedly (115.7 ± 17.6 vs. 101.5 ± 16.4 ng/mL; p < 0.001). Only successful kidney transplantation allowed it to get down to the values noted in controls (74.8 ± 16.0 vs. 72.6 ± 20.7 ng/mL; n.s.). The level of subcutaneous adipose tissue chemerin mRNA in CKD patients was not different than in patients of the control group. The study demonstrates that elevated serum chemerin concentration in CKD patients: (a) is related to kidney function, but not to increased chemerin production by subcutaneous adipose tissue, and (b) it can be efficiently corrected by hemodialysis treatment and normalized by kidney transplantation.
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Tecido Adiposo/metabolismo , Proteína C-Reativa/metabolismo , Quimiocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Transplante de Rim/métodos , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Testes de Função Renal , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: A high level of circulating PCSK9 binds to the LDL receptor, reduces its cell's surface density and leads to hypercholesterolemia. The aim of this study was to examine the circulating PCSK9 level in patients with kidney disease. METHODS: Out of the patients treated in our Departments we selected: (a) 44 patients with CKD stage 3 and 4 (b) 29 patients with CKD stage 5 on maintenance hemodialysis treatment; and (c) 20 patients after successful renal transplantation. Thirty-four subjects, without CKD formed the control group. Serum biochemical parameters' concentrations were assayed by a certified laboratory. Serum PCSK9 concentration was estimated by a commercially available ELISA kit. RESULTS: The mean serum concentration of PCSK9 in patients with kidney disease was higher than in the control group (238.7 ± 64.5 vs. 536.7 ± 190.4; p < 0.001). A strong negative correlation between serum PCSK9 concentration and eGFR was found (r = -0.66; p < 0.001), as well as between serum concentrations of PCSK9 and total- (r = 0.482; p < 0.05) or LDL-cholesterol (r = 0.533; p < 0.05), but exclusively in patients not receiving statins. The elevated serum concentration of PCSK9 in patients before hemodialysis session declined afterwards, reaching the values observed in patients after kidney transplantation and in the control group. CONCLUSION: The circulating PCSK9 concentration is increased in patients with CKD; however, this is not accompanied by hypercholesterolemia. The positive correlations between PCSK9/TCh and PCSK9/LDL-Ch have been found only in patients not treated with statins. The elevated circulating PCSK9 level is corrected by maintenance hemodialysis treatment and normalized by a successful kidney transplantation.
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Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Transplante de Rim , Pró-Proteína Convertases/sangue , Diálise Renal , Serina Endopeptidases/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , LDL-Colesterol/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9 , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapiaRESUMO
The results of clinical trials show that up to one-third of patients who are eligible for cardiac resynchronization therapy (CRT) do not benefit from biventricular pacing. The reasons vary, including technical problems related to left ventricle pacing lead placement in the appropriate branch of the coronary sinus. Herein, we present a case report of a patient with heart failure with reduced ejection fraction and left bundle branch block, in whom a poor coronary sinus bed made implantation of classic biventricular CRT impossible, but in whom, alternatively, rescue-performed left bundle branch area pacing allowed effective electrical and mechanical cardiac resynchronization. The report confirms that left bundle branch area pacing may be a rational alternative in such cases.
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The optimal structure of the acute ischaemic stroke treatment network is unknown and eagerly sought. To make it most effective, different treatment and transportation strategies have been developed and investigated worldwide. Since only a fraction of acute stroke patients with large vessel occlusion are treated, a new entity-thrombectomy-capable stroke centre (TCSC)-was introduced to respond to the growing demand for timely endovascular treatment. The purpose of this study was to present the early experience of the first 70 patients treated by mechanical means in a newly developed cardiac Cathlab-based TCSC. The essential safety and efficacy measures were recorded and compared with those reported in the invasive arm of the HERMES meta-analysis-the largest published dataset on the subject. We found no significant differences in terms of clinical and safety outcomes, such as early neurological recovery, level of functional independence at 90 days, symptomatic intracranial haemorrhage, parenchymal haematoma type 2, and mortality. These encouraging results obtained in the small endovascular centre may be an argument for the introduction of the TCSC into operating stroke networks to increase patient access to timely treatment and to improve clinical outcomes.
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Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/terapia , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Trombectomia/métodos , Terapia Trombolítica , Resultado do TratamentoRESUMO
BACKGROUND: The use of subcutaneous implantable cardioverter-defibrillators (S-ICD) has been growing in Poland since 2014. The Polish Registry of S-ICD Implantations was run by the Heart Rhythm Section of the Polish Cardiac Society between May 2020 and September 2022 to monitor the implementation of that therapy in Poland. AIMS: To investigate and present the state-of-the-art of S-ICD implantation in Poland. METHODS: Implanting centers reported clinical data of patients undergoing S-ICD implantations and replacements, including age, sex, height, weight, underlying disease, history of pacemaker and defibrillator implantations, indications for S-ICD, electrocardiographical parameters, procedural techniques, and complications. RESULTS: Four hundred and forty patients undergoing S-ICD implantation (411) or replacement (29) were reported by 16 centers. Most patients were in New York Heart Association class II (218 patients, 53%) or I (150 patients, 36.5%). Left ventricular ejection fraction was 10%-80%, median (IQR) was 33% (25%-55%). Primary prevention indications were present in 273 patients (66.4%). Non-ischemic cardiomyopathy was reported in 194 patients (47.2%). The main reason for the choice of S-ICD were: young age (309, 75.2%), risk of infectious complications (46, 11.2%), prior infective endocarditis (36, 8.8%), hemodialysis (23, 5.6%), and immunosuppressive therapy (7, 1.7%). Electrocardiographic screening was performed in 90% of patients. The rate of adverse events was low (1.7%). No surgical complications were observed.
Assuntos
Desfibriladores Implantáveis , Humanos , Polônia , Desfibriladores Implantáveis/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Sistema de Registros , Morte Súbita Cardíaca/prevenção & controleRESUMO
BACKGROUND: Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. METHODS: This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. RESULTS: The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. CONCLUSION: Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.
Assuntos
Antiarrítmicos , Fibrilação Atrial , Feminino , Humanos , Masculino , Amiodarona , Antazolina/efeitos adversos , Antazolina/farmacologia , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacologia , Fibrilação Atrial/tratamento farmacológico , Cardioversão Elétrica , Propafenona/efeitos adversos , Propafenona/farmacologia , Resultado do Tratamento , Fatores Sexuais , Estudos Multicêntricos como AssuntoRESUMO
The interventional treatment of acute ischemic stroke with large vessel occlusion has revolutionized patient care in recent years. The Mechanical Thrombectomy Pilot Program in Poland is due to end soon. It seems the right time to summarize the achievements and name the problems of a centralized stroke care system and decide what future model of treatment and transportation to implement. In order to provide the best care for our patients, it is crucial to establish the actual needs in stroke and tailor the mechanical thrombectomy system structure accordingly. The analysis of data from well-organized health systems in the world suggests that to deliver adequate numbers of mechanical thrombectomy to stroke patients in Poland, we would need to at least double the number of procedures currently performed. To achieve this, an essential system reorganization and adjustments are required, with special emphasis on the number of mechanical thrombectomy centers and transportation models. The strengths and weaknesses of two dominant transportation models (mothership and drip-and-ship) are herein discussed, and a proposal on how to build an efficient and cost-effective mechanical thrombectomy stroke network in Poland is put forward. The article is an invitation to open an interdisciplinary discussion on the best treatment model of acute ischemic stroke patients requiring mechanical thrombectomy in Poland.
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Due to the negative results of randomized aspiration thrombectomy studies, its role in myocardial infarction has been limited to high thrombus burden and/or failed vessel recanalization, with little technological advancement over the last years. In contrast, there has been rapid progress in mechanical thrombectomy in stroke, which is understandable as most ischemic cerebrovascular accidents have an embolic etiology.We present three transradial procedures wherein neurointerventional catheters were used as a first-line device for en bloc removal of large clots lodged distally in tortuous coronary anatomy. First-pass reperfusion was achieved in all the cases, without dissection, distal embolization, or the no reflow phenomenon. Learning objective: In the case of large clots, where coronary aspiration devices fail, neurointerventional catheters may be considered as a rescue strategy. They provide large aspiration lumen and excellent trackability with atraumatic design. Many other neurointerventional techniques can be easily adopted into the coronary armamentarium, possibly increasing the safety and efficacy of thrombus aspiration.
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There are reports documenting that electromagnetic waves generated by deep brain stimulation devices can interfere with cardiac pacemakers. This might be even a life-threatening problem in cardiac pacemaker-dependent patients. Herein, we present a case report on a patient with bilaterally implanted deep brain stimulation devices, who concomitantly had the indications for permanent cardiac pacing. The report shows that a leadless AV pacemaker may be a safe and reasonable option in these cases.
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Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Próteses e Implantes , Encéfalo , Desenho de EquipamentoRESUMO
Catheter-induced dissections (CID) of coronary arteries and/or the aorta are among the most dangerous complications of percutaneous coronary procedures, yet the data on their risk factors are anecdotal. Logistic regression and five more advanced machine learning techniques were applied to determine the most significant predictors of dissection. Model performance comparison and feature importance ranking were evaluated. We identified 124 cases of CID in electronic databases containing 84,223 records of diagnostic and interventional coronary procedures from the years 2000-2022. Based on the f1-score, Extreme Gradient Boosting (XGBoost) was found to have the optimal balance between positive predictive value (precision) and sensitivity (recall). As by the XGBoost, the strongest predictors were the use of a guiding catheter (angioplasty), small/stenotic ostium, radial access, hypertension, acute myocardial infarction, prior angioplasty, female gender, chronic renal failure, atypical coronary origin, and chronic obstructive pulmonary disease. Risk prediction can be bolstered with machine learning algorithms and provide valuable clinical decision support. Based on the proposed model, a profile of 'a perfect dissection candidate' can be defined. In patients with 'a clustering' of dissection predictors, a less aggressive catheter and/or modification of the access site should be considered.
Assuntos
Aorta , Intervenção Coronária Percutânea , Humanos , Feminino , Intervenção Coronária Percutânea/métodos , Catéteres , Aprendizado de Máquina , AlgoritmosRESUMO
BACKGROUND: Only the incidence, management, and prognosis of catheter-induced coronary artery and aortic dissections have been systematically studied until now. We sought to evaluate their mechanisms, risk factors, and propagation causes. METHODS: Electronic databases containing 76,104 procedures and complication registries from 2000-2020 were searched and relevant cineangiographic studies adjudicated. RESULTS: Ninety-six dissections were identified. The overall incidence was 0.126%, and 0.021% for aortic injuries. The in-hospital mortality rate was 4.2%, and 6.25% for aortic dissections. Compared to the non-complicated population, patients with dissection were more often female (48% vs. 34%, p = 0.004), with a higher prevalence of comorbidities such as hypertension (56% vs. 25%, p < 0.001) or chronic kidney disease (10% vs. 4%, p = 0.002). They more frequently presented with acute myocardial infarction (72% vs. 43%, p < 0.001), underwent percutaneous coronary intervention (85% vs. 39%, p < 0.001), and were examined with a radial approach (77% vs. 65%, p = 0.011). The most prevalent predisposing factor was small ostium diameter and/or atheroma. Deep intubation for support, catheter malalignment, and vessel prodding were the most frequent precipitating factors. Of the three dissection mechanisms, 'wedged contrast injection' was the commonest (the exclusive mechanism of aortic dissections). The propagation rate was 30.2% and led to doubling of coronary occlusions and aortic extensions. The most frequent progression triggers were repeat injections and unchanged catheter. In 94% of cases, dissections were inflicted by high-volume operators, with ≥ 5-year experience in 84% of procedures. The annual dissection rate increased over a 21-year timespan. CONCLUSIONS: Catheter-induced dissection rarely came unheralded and typically occurred during urgent interventions performed in high-risk patients by experienced operators.
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INTRODUCTION: Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of antazoline, a firstgeneration antihistamine, for cardioversion of recentonset AF in the setting of an emergency department. PATIENTS AND METHODS: This multicenter, retrospective registry covered 1365 patients (median [interquartile range] age, 69.0 [61.0-76.0] years, 53.1% men) with newonset AF submitted to urgent pharmacological cardioversion. AAD allocation was performed by the attending physician: antazoline alone was utilized in 600 patients (44%), amiodarone in 287 (21%), propafenone in 150 (11%), and ≥2 AADs in 328 patients (24%). Antazoline in monotherapy or combination was administered to 897 patients (65.7%). Matched antazoline and nonantazoline groups were identified using propensity score matching (PSM, n = 330). The primary end point was return to sinus rhythm within 12 hours after initiation of the treatment. RESULTS: Before PSM, antazoline alone was superior to amiodarone (78.3% vs 66.9%; relative risk [RR], 1.17; 95% CI, 1.07-1.28; P <0.001) and comparable to propafenone (78.3% vs 72.7%; RR, 1.08; 95% CI, 0.97-1.20; P = 0.14) in terms of rhythm conversion rate. In the postPSM population, the rhythm conversion rate was higher among patients receiving antazoline alone than in the nonantazoline group (84.2% vs 66.7%; RR, 1.26; 95% CI, 1.11-1.43; P <0.001), and the risk of adverse events was comparable (P = 0.2). CONCLUSIONS: Antazoline appears to be an efficacious agent for termination of AF in realworld setting. Randomized controlled trials are required to evaluate its safety in specific patient populations.
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Amiodarona , Antazolina , Fibrilação Atrial , Idoso , Amiodarona/efeitos adversos , Antazolina/efeitos adversos , Antazolina/uso terapêutico , Antiarrítmicos/efeitos adversos , Cardioversão Elétrica , Feminino , Humanos , Masculino , Propafenona/uso terapêutico , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Pharmacological cardioversion (PCV) is commonly a primary option for termination of recent-onset atrial fibrillation (AF) in emergency departments (ED). This is a subanalysis of the CANT II study, evaluating the effectiveness and safety of antazoline in patients (n = 777) at three stages of chronic kidney disease (CKD): Group I > 60 mL/min (n = 531), Group II 45−59 mL/min (n = 149), and Group III < 45 mL/min (n = 97). Patients in Group III were older and with a higher prevalence of co-morbidities; however, we did not find statistically significant differences in the overall effectiveness of PCV in comparison with the other groups. In patients receiving amiodarone, the PCV success rate was similar in all the studied groups, but along with a renal function decline, it decreased in patients receiving antazoline (79.1 vs. 35%; p < 0.001), and it increased almost significantly in patients receiving propafenone (69.9 vs. 100%; p = 0.067). In patients in Group I, antazoline restored a sinus rhythm as effectively as propafenone and amiodarone; however, in patients in Group III, both antazoline and amiodarone became less effective in restoring a sinus rhythm than propafenone (p = 0.002 and p = 0.034, respectively). The rate of safety endpoint was the highest in patients in Group III (eGFR < 45 mL/min), and it was significantly higher than in patients in Groups I and II (p = 0.008 and p = 0.036, respectively). We did not observe antazoline-related adverse events in any of the studied groups of patients. This real-world registry analysis revealed a different influence of CKD on the effectiveness of individual drugs, and while propafenone and amiodarone maintained their AF termination efficacy, antazoline became significantly less effective in restoring sinus rhythm.
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Amiodarona , Antazolina , Fibrilação Atrial , Insuficiência Renal Crônica , Amiodarona/uso terapêutico , Antazolina/efeitos adversos , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Cardioversão Elétrica , Feminino , Humanos , Masculino , Propafenona/efeitos adversos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Resultado do TratamentoRESUMO
This study evaluates whether the presence of cardiovascular risk factors (CRFs) affects functional and morphological responses to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular age-related macular degeneration (nAMD). Retrospective analysis included 98 treatment-naïve eyes followed for at least 12 months. Patients received intravitreal injections of ranibizumab or aflibercept with the dosage and regimen set according to each manufacturer's recommendations for their product. Parameters evaluated at each follow-up visit included best-corrected visual acuity and central retinal thickness. Additionally, the presence of the following CRFs was evaluated: male sex, age of older than 70 years, history of current or past smoking, systemic arterial hypertension, diabetes mellitus, total hypercholesterolemia, low-density lipoprotein hypercholesterolemia, high-density lipoprotein concentration of 45 mg/dL or less, atherogenic dyslipidemia, family history of cardiovascular disease, and chronic kidney disease. A statistically significant better letter gain in visual acuity (p = 0.012) and greater percentage of responders (p = 0.035)-that is patients in whom best corrected visual acuity was stabilized or improved at 12 months-were noted among patients without a diagnosis of arterial hypertension. A statistically significant better mean visual improvement was also achieved in patients with higher total cholesterol plasma levels (p = 0.004), but this finding was not reflected in the significantly higher percentage of responders. The presence of remaining analyzed risk factors did not substantially affect the results of treatment. Systemic arterial hypertension is an independent factor leading to a poor functional outcome following anti-VEGF therapy in patients with nAMD. Effects of anti-VEGF treatment in patients with high total cholesterol levels should be analyzed in further research.
RESUMO
We compared the effects of right ventricular (RVP; n = 26) and His bundle (HBP; n = 24) pacing in patients with atrioventricular conduction disorders and preserved LVEF. Postoperatively (1D), and after six months (6M), the patients underwent global longitudinal strain (GLS) and peak systolic dispersion (PSD) evaluation with 2D speckle-tracking echocardiography, assessment of left atrial volume index (LAVI) and QRS duration (QRSd), and sensing/pacing parameter testing. The RVP threshold was lower than the HBP threshold at 1D (0.65 ± 0.13 vs. 1.05 ± 0.20 V, p < 0.001), and then it remained stable, while the HBP threshold increased at 6M (1.05 ± 0.20 vs. 1.31 ± 0.30 V, p < 0.001). The RVP R-wave was higher than the HBP R-wave at 1D (11.52 ± 2.99 vs. 4.82 ± 1.41 mV, p < 0.001). The RVP R-wave also remained stable, while the HBP R-wave decreased at 6M (4.82 ± 1.41 vs. 4.50 ± 1.09 mV, p < 0.02). RVP QRSd was longer than HBP QRSd at 6M (145.0 ± 11.1 vs. 112.3 ± 9.3 ms, p < 0.001). The absolute value of RVP GLS decreased at 6M (16.32 ± 2.57 vs. 14.03 ± 3.78%, p < 0.001), and HBP GLS remained stable. Simultaneously, RVP PSD increased (72.53 ± 24.15 vs. 88.33 ± 30.51 ms, p < 0.001) and HBP PSD decreased (96.28 ± 33.99 vs. 84.95 ± 28.98 ms, p < 0.001) after 6 months. RVP LAVI increased (26.73 ± 5.7 vs. 28.40 ± 6.4 mL/m2, p < 0.05), while HBP LAVI decreased at 6M (30.03 ± 7.8 vs. 28.73 ± 8.7 mL/m2, p < 0.01). These results confirm that HBP does not disrupt ventricular synchrony and provides advantages over RVP.