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1.
JACC Heart Fail ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878009

RESUMO

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. OBJECTIVES: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk). METHODS: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6]). RESULTS: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m2, 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily. CONCLUSIONS: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone; NCT04676646).

2.
Artigo em Inglês | MEDLINE | ID: mdl-37799003

RESUMO

BACKGROUND: Acutely ill older patients frequently suffer not only from their acute disease, but also polymorbidity and frailty. Dehydration is another typical symptom, usually occurring in its both forms: low-intake dehydration and volume depletion. POCUS is goal-directed bedside ultrasound examination and several studies refer to its positive impact on hydration assessment. The aim of our study was to determine whether POCUS might influence (de)hydration diagnostics and/or treatments in older patients with acute illness. METHODS: We randomized 120 acutely ill patients, aged ≥65 years, into POCUS and non-POCUS groups. All participants underwent routine laboratory tests, including haematocrit, serum and urine osmolality, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, and C-reactive protein (CRP). POCUS was performed twice during the first two days to determine chest and abdominal status, with inferior vena cava (IVC) measurements. Length of hospital stay (HL) and consumption of infused fluids (CIF) was evaluated too. Data were analysed with exploratory methods and appropriate statistics. RESULTS: Among all participants, the serum osmolality significantly correlated with age, BUN, creatinine and CIF. HL correlated with CRP and CIF. No significant correlations between IVC and other followed parameters were found. The POCUS group consumed significantly less infused fluids than the non-POCUS group, what could be influenced by POCUS examination of defined body compartments. CONCLUSION: Dehydration is a common feature in older individuals and its diagnostics is rather complicated. The role of POCUS in assessing hydration status remains unclear. However, our study showed, that ultrasound assessment provides next important information for comprehensive understanding of clinical status in older patients and can be beneficial for optimizing the treatment strategy, including fluid management decisions.

3.
Vnitr Lek ; 69(1): 14-22, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36931877

RESUMO

In 2022, the European Society of Cardiology has published updated guidelines for the cardiovascular evaluation and management of patients undergoing non-cardiac surgery. In this article we briefly summarize the most important recommendations with an emphasis on their use in everyday clinical practice - from the complex assessment of cardiovascular risk and prediction of cardiovascular complications, through the indication of basic paraclinical examinations, the importance of biomarkers, adjustments to pharmacotherapy of heart failure, adjustments to anticoagulant and antiplatelet therapy, to other specifics of individual cardiovascular and other diseases and their importance in the perioperative period. Knowledge and use of these recommendations have the potential to improve the prognosis of patients undergoing various types of surgical procedures.


Assuntos
Doenças Cardiovasculares , Assistência Perioperatória , Procedimentos Cirúrgicos Operatórios , Humanos , Cardiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/prevenção & controle , Medição de Risco , Europa (Continente) , Sociedades Médicas
4.
Vnitr Lek ; 69(1): 57-63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36931883

RESUMO

The article summarizes new advances in cardiology published in 2022, which have an impact to everyday practice of not only internists and cardiologists. The administration of polypill to patients after myocardial infarction (SECURE study), early pharmacotherapy of hypertension in pregnant women with blood pressure exceeding 140/90 mmHg (CHAP study), or the administration of dapagliflozin to patients with heart failure with preserved or mildly reduced ejection fraction (DELIVER study) have been shown to be effective. Patients with heart failure do not have to limit their sodium intake (SODIUM-HF study), on the contrary, they benefit from up-titration of guideline-recommended drugs to the maximum tolerated doses as quickly as possible (STRONG-HF study). For antihypertensives, it does not matter whether they are taken in the morning or in the evening (TIME study), nor has there been found any difference in the incidence of cardiovascular events with hydrochlorothiazide and chlortalidone (DCP study). In patients with increased cardiovascular risk, highly sensitive troponin should be measured before non-cardiac surgery as well as 24 and 48 hours after surgery to detect perioperative myocardial infarction. Different blood pressure and oxygenation targets in patients after resuscitation for out-of-hospital cardiac arrest do not affect the outcomes of their treatment.


Assuntos
Cardiologia , Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Gravidez , Humanos , Feminino , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico
5.
Vnitr Lek ; 68(6): 376-386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36316199

RESUMO

Arterial hypertension together with dyslipidemia, diabetes and smoking are the most severe risk factors for cardiovascular (CV) disease. The Czech Republic is among the countries with a high risk of cardiovascular disease. To reduce cardiovascular mortality and morbidity in our patients, a comprehensive approach to treatment and, in most cases, aggressive control of all risk factors is needed. This article summarizes current diagnostic and therapeutic procedures for arterial hypertension and dyslipidaemia, as well as the concept of vascular age, which can help us to communicate CV risk with patients.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Dislipidemias , Hipertensão , Humanos , Dislipidemias/tratamento farmacológico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Doenças Cardiovasculares/complicações , Fatores de Risco
6.
Endocrine ; 76(1): 142-150, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35147923

RESUMO

PURPOSE: To evaluate laboratory and clinical results after unilateral adrenalectomy in patients with primary aldosteronism (PHA). METHODS: A cross-sectional analysis was performed using data from patients who underwent transperitoneal laparoscopic adrenalectomy for PHA, between January 2008 and December 2019. Surgical indications were based on adrenal venous sampling without ACTH stimulation. Analyses included patient demographics; preoperative clinical, pharmacological, laboratory, and radiological data; and postoperative results assessed after a median of 4 months. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication, thus enabling standardized comparison of dosage between the drug classes. Statistical assessments included univariable and multivariable logistic regression analysis. RESULTS: This study enrolled 87 patients. The patients were taking 5.4 DDD of antihypertensive medication before surgery, and 3.0 DDD after surgery. Complete biochemical success of surgery was reached 67 patients (77%), 19 patients (22%) had partial biochemical success. Complete clinical success with normalization of blood pressure and withdrawal of all antihypertensive drugs was achieved in 19 patients (22%). 57 patients (65%) exhibited a reduction of DDD after surgery and/or improvement of blood pressure-partial clinical success. Thus, in 76 (87%) of all enrolled patients, surgery had an overall positive effect on hypertension control. Multivariable logistic regression showed that complete clinical success was independently associated with female gender and baseline sum of antihypertensive drugs DDD < 4. CONCLUSION: A majority of patients undergoing unilateral adrenalectomy for PHA achieved markedly improved hypertension control, despite almost halving their antihypertensive medication. Almost a quarter of patients were cured and able to cease using all antihypertensive drugs.


Assuntos
Hiperaldosteronismo , Hipertensão , Adrenalectomia , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/cirurgia , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipertensão/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-32495751

RESUMO

OBJECTIVES: Adipose tissue produces a number of adipokines that have metabolic effect. Visfatin is a recently discovered adipokine whose concentration in plasma increases in obesity. It is also a proinflammatory mediator that promotes atherosclerosis and plays a role in plaque destabilization. The aim of this study was to evaluate an assay for the determination of visfatin in human plasma and to investigate its clinical relevance as a marker of acute coronary syndrome (ACS) in a young population (Men under 45 y, Women under 55 y). DESIGN AND METHODS: We clinically tested a sandwich ELISA assay in young individuals with acute myocardial infarction (n=36) vs. a control group (n=21). The control sample was a healthy proband without inflammation, hepatic or renal injury and under 55 years of age. RESULTS: Visfatin in plasma was able to differentiate the control group from young patients with acute myocardial infarction (5 vs. 27 ng/L). Visfatin in the plasma of acute myocardial infarction (AMI) probands, correlated in individuals with acute coronary syndrome was related to plasma glucose (r=0.47; P=0.01), type 2 diabetes mellitus (r=0.65; P=0.01), plasma creatinine concentration (r=0.3, P=0.02), hsCRP (r=0.29; P=0.03), BMI values (r=0.18; P=0.04), triglycerides (r=0.5; P=0.01) and NT-proBNP (r=0.21; P=0.04). In healthy subjects, these relations were not found. ROC analysis: visfatin cut-off concentration was 20 ng/L with a sensitivity of 84% and a specificity of 90%. The area under the curve (AUC) of cTNI was 0.96, the AUC of visfatin was 0.96. Thus, there was no difference. CONCLUSION: We conclude that visfatin in serum may be a new independent potential marker of AMI.


Assuntos
Adipocinas/sangue , Biomarcadores/sangue , Citocinas/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Nicotinamida Fosforribosiltransferase/sangue , Adipocinas/metabolismo , Adulto , Biomarcadores/metabolismo , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/metabolismo
8.
Clin Cardiol ; 42(8): 720-727, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31119751

RESUMO

BACKGROUND: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. METHODS: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 µmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers. RESULTS: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group). CONCLUSION: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.


Assuntos
Alopurinol/administração & dosagem , Insuficiência Cardíaca/complicações , Hiperuricemia/tratamento farmacológico , Pontuação de Propensão , Sistema de Registros , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Causas de Morte , República Tcheca/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Supressores da Gota/administração & dosagem , Insuficiência Cardíaca/mortalidade , Humanos , Hiperuricemia/sangue , Hiperuricemia/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Ácido Úrico/sangue
9.
PLoS One ; 13(12): e0208947, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532129

RESUMO

Purines are essential molecules for all forms of life. In addition to constituting a backbone of DNA and RNA, purines play roles in many metabolic pathways, such as energy utilization, regulation of enzyme activity, and cell signaling. The supply of purines is provided by two pathways: the salvage pathway and de novo synthesis. Although purine de novo synthesis (PDNS) activity varies during the cell cycle, this pathway represents an important source of purines, especially for rapidly dividing cells. A method for the detailed study of PDNS is lacking for analytical reasons (sensitivity) and because of the commercial unavailability of the compounds. The aim was to fully describe the mass spectrometric fragmentation behavior of newly synthesized PDNS-related metabolites and develop an analytical method. Except for four initial ribotide PDNS intermediates that preferentially lost water or phosphate or cleaved the forming base of the purine ring, all the other metabolites studied cleaved the glycosidic bond in the first fragmentation stage. Fragmentation was possible in the third to sixth stages. A liquid chromatography-high-resolution mass spectrometric method was developed and applied in the analysis of CRISPR-Cas9 genome-edited HeLa cells deficient in the individual enzymatic steps of PDNS and the salvage pathway. The identities of the newly synthesized intermediates of PDNS were confirmed by comparing the fragmentation patterns of the synthesized metabolites with those produced by cells (formed under pathological conditions of known and theoretically possible defects of PDNS). The use of stable isotope incorporation allowed the confirmation of fragmentation mechanisms and provided data for future fluxomic experiments. This method may find uses in the diagnosis of PDNS disorders, the investigation of purinosome formation, cancer research, enzyme inhibition studies, and other applications.


Assuntos
DNA/biossíntese , Purinas/biossíntese , RNA/biossíntese , Espectrometria de Massas em Tandem , Sistemas CRISPR-Cas , Cromatografia Líquida , DNA/química , Edição de Genes , Células HeLa , Humanos , Purinas/química , RNA/química
10.
Artigo em Inglês | MEDLINE | ID: mdl-29042710

RESUMO

OBJECTIVE: Paroxysmal hypertension or pseudopheochromocytoma is quite a common problem in clinical practice. The optimal treatment for this condition has not been established. This study sought to investigate whether sertraline (a selective serotonin reuptake inhibitor) reduces the symptoms. METHODS: We enrolled 64 patients referred to our department between April 2008 and October 2014 for symptomatic paroxysmal hypertension. Patients received sertraline, 50 mg once daily, in addition to their current medication. The effect of the treatment was assessed during their next clinical visit at least 3 months later. RESULTS: Of the 64 patients, 57 (89%) also had sustained arterial hypertension. Mean office baseline blood pressure (BP) was 147.6/83.8 mmHg and patients used a mean of 3.1 antihypertensive drugs. Five patients did not start using sertraline and three were lost to follow-up. Of the 56 patients who started using sertraline and who came for check up, clinical improvement was observed in 42 (75%) patients - symptoms of paroxysmal hypertension fully subsided in 28 (50%) and were partially reduced in 14 (25%) . Side effects or intolerance leading to discontinuation of treatment occurred in 7 patients (12.5%). Mean office BP in patients using sertraline decreased by 12.8/7.4 mmHg (P<0.001 for both). CONCLUSIONS: Sertraline effectively removed or reduced symptoms of paroxysmal hypertension in the majority of patients who used this treatment.


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Sertralina/administração & dosagem , Idoso , Esquema de Medicação , Feminino , Humanos , Masculino , Feocromocitoma/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-27108603

RESUMO

OBJECTIVES: Omentin-1 is an adipokine which could have a protective role against the manifestation of atherosclerosis. Only limited data are available on omentin-1 serum values in patients with premature clinical manifestations of atherosclerosis. DESIGN AND METHODS: We tested omentin-1 in human serum by ELISA method in 61 individuals with a premature manifestation of coronary artery disease (CAD), 40 patients with metabolic syndrome and 40 healthy control subjects. RESULTS: Omentin-1 serum levels were significantly lower in patients with CAD (103.1±62.7 mg/L) compared to metabolic syndrome (668.2±339.6 mg/L) and healthy subjects (623.0±373.5 mg/L) (P < 0.01). In CAD patients, omentin-1 serum levels did not differ between patients sampled in the acute phase of myocardial infarction (n = 28; 110.3±82.4 mg/L) and in the chronic phase several months or years after myocardial infarction (n = 33; 97.0±39.3 mg/L) (P = 0.41). We found a weak positive correlation between omentin-1 and body mass index (r = 0.21, P = 0.014). No significant correlation was found between peak cardiac troponin T and omentin-1 (correlation coefficient r = 0.118, P = 0.406). CONCLUSION: Serum omentin-1 seems to be a useful biomarker of coronary artery disease across the whole age spectrum.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Citocinas/metabolismo , Lectinas/metabolismo , Síndrome Metabólica/diagnóstico , Adolescente , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Curva ROC , Reprodutibilidade dos Testes , Adulto Jovem
12.
PLoS One ; 10(2): e0117142, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25710625

RESUMO

BACKGROUND: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the "obesity paradox" on a large cohort with long-term follow-up are lacking. METHODS: Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5-25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. RESULTS: In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26-1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09-1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11-1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. CONCLUSION: These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.


Assuntos
Insuficiência Cardíaca/patologia , Obesidade/complicações , Doença Aguda , Idoso , Índice de Massa Corporal , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Modelos de Riscos Proporcionais , Análise de Sobrevida
13.
Artigo em Inglês | MEDLINE | ID: mdl-25471827

RESUMO

INTRODUCTION: Primary hyperaldosteronism is a common cause of secondary hypertension. In patients with proven unilateral overproduction of aldosterone adrenalectomy can cure hyperaldosteronism with high probability and a positive effect on hypertension. The aim of the study was to determine the effects of unilateral adrenalectomy on blood pressure and laboratory parameters. The secondary objective was to identify parameters that would allow the prediction of hypertension cure. METHODS: We performed a cross-sectional analysis of the data of patients who underwent unilateral adrenalectomy for primary aldosteronism at the Department of Urology of University Hospital Olomouc in the years 2000-2011. We assesed the preoperative clinical conditions of patients, the results of biochemical and radiological examinations, course of the surgery and post-operative course including laboratory and clinical parameters during the 12 months postoperatively. RESULTS: 62 patients underwent adrenalectomy for primary aldosteronism in this period. Four patients were excluded from the study due to surprising histology (myelolipoma in 2, carcinoma in 2), seven patients had incomplete postoperative data. The statistical analysis therefore included 51 patients, of which 57% were females. CT or MRI was performed in all patients; 63% patients underwent superselective catheterization of adrenal veins (AVS). Adrenalectomy was performed in all cases laparoscopically. Histology most often showed adrenal hyperplasia (59%), adenoma was detected in 37% and adenoma on the basis of micronodular hyperplasia in 4%. Twelve months after surgery the antihypertensive drugs were discontinued in 17/51 (33%) and the number or dose of antihypertensive drugs was reduced in 25/51 (49%). Normokalemia and normalisation of the aldosterone-renin ratio (ARR) was detected in 92% and 84% of the patients. Performing AVS did not statistically significantly influence the rate of blood pressure control or normalization of ARR, which is probably due to small study size. This study demonstrated a better effect of surgery on blood pressure in younger patients. CONCLUSIONS: Unilateral adrenalectomy had a positive effect in 82% of the patients operated for primary aldosteronism and lead to either blood pressure normalization or reduction of the antihypertensive medication.


Assuntos
Glândulas Suprarrenais/patologia , Adrenalectomia/métodos , Anti-Hipertensivos/uso terapêutico , Hiperaldosteronismo/cirurgia , Hipertensão/cirurgia , Glândulas Suprarrenais/cirurgia , Adulto , Idoso , Pressão Sanguínea , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Genet Test Mol Biomarkers ; 18(9): 599-604, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25093390

RESUMO

METHODS: The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E1 for detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T>C; rs2046934), P2Y12 (34C>T; rs6785930), COX-1 (-842A>G; rs10306114), GPVI (13254T>C; rs1613662), and GPIbA (5T>C; rs2243093) polymorphisms, DNA of patients with AIM was tested by real-time-polymerase chain reaction and melting curve analysis using the LightCycler 480 analyzer (Roche Diagnostics). RESULTS: The cut-off points used for patients with effective ASA therapy are 25% of aggregated platelets and 220 area under the curve (AUC)/min if LTA or MEA, respectively. The cut-off points used for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively. Both LTA and MEA found that aspirin and thienopyridine therapies failed in 14.51% and 25.8%, respectively. The data were statistically processed using the SPSS version 15 software (SPSS, Inc.). Associations between receptor mutation status and response to therapy were assessed with Fisher's exact test. The significance level was set at 0.05. CONCLUSION: The aim of our work was to use the two functional laboratory methods described earlier to assess both aspirin and thienopyridine resistance and to determine the contribution of genetic polymorphisms of platelet receptors to resistance to antiplatelet therapy in AIM. Fisher's exact test showed a significant statistical correlation between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of COX1_A1 (-A842G). Fisher's exact test showed no statistically significant correlations between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of GP1bA (-5T>C) and GP6 (T13254C). Fisher's exact test showed no statistically significant correlation between mutational statuses of the receptors P2RY12 (i-T744C), P2RY12 (C34T), GP1bA (-5T>C), or GP6 (T13254C) and response to antiplatelet therapy with 75 mg of clopidogrel.


Assuntos
Antígenos de Plaquetas Humanas/genética , Resistência a Medicamentos , Infarto do Miocárdio , Inibidores da Agregação Plaquetária/administração & dosagem , Mutação Puntual , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Projetos Piloto
15.
Int J Cardiovasc Imaging ; 27(3): 343-53, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20725789

RESUMO

Patients with ischemic heart disease and depressed left ventricular (LV) ejection fraction (LVEF) develop varying degrees of LV remodeling after cardiac surgical revascularization. Fifty-three patients with stable ischemic heart disease and impaired LV function (LVEF 34.9 ± 4%) were prospectively followed up for 24 months. Thirty-seven patients underwent coronary artery bypass grafting (CABG), 16 patients were treated conservatively. Cardiac magnetic resonance imaging (MRI) and SPECT were performed at baseline and after 12 and 24 months of follow-up. The patients were divided into responders and non-responders depending on the degree of LVEF improvement at 24 months follow-up (>5%-responders). MRI with ≤5 segments with DE/wall thickness ratio (DEWTR) ≥50% predicted LV reverse remodeling with a sensitivity of 86% and a specificity of 75% (AUC 0.81). An MRI finding of ≤2 segments with the DEWTR ≥75% had a corresponding sensitivity of 71% and specificity of 67% (AUC 0.75) while fixed perfusion defect on SPECT <16.5% of LV predicted reverse remodeling with a sensitivity of 64% and a specificity of 69% (AUC 0.64). A preoperative number of segments with the DE/wall thickness ratio of ≥50 and ≥75% obtained by MRI, was found to be a better predictor of left ventricular reverse remodeling than fixed perfusion defect by SPECT. No other MRI or SPECT parameter predicted LVEF improvement at 24 months after CABG.


Assuntos
Cardiomiopatias/terapia , Fármacos Cardiovasculares/uso terapêutico , Ponte de Artéria Coronária , Imageamento por Ressonância Magnética , Isquemia Miocárdica/terapia , Tomografia Computadorizada de Emissão de Fóton Único , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Angiografia Coronária , República Tcheca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Recuperação de Função Fisiológica , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento
18.
J Hypertens ; 25(7): 1427-31, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17563565

RESUMO

OBJECTIVES: Detection of free plasma metanephrines seems to be the most exact method for biochemical diagnosis of pheochromocytoma, but their diagnostic efficacy in the common low-risk clinical settings is debated. METHODS: A cross-sectional multicentre study including 1260 subjects assessed the diagnostic efficacy of free plasma metanephrine and normetanephrine in low-risk patients screened for resistant or markedly accelerated hypertension, paroxysmal hypertension, 'flushes' and, in a small proportion, for adrenal incidentaloma or genetic predisposition to pheochromocytoma. RESULTS: Pheochromocytoma was identified and verified by histology in 25 subjects (2%), with the diagnosis not confirmed by long-term follow-up or use of imaging techniques in the remaining 1235 individuals. The combined assay of free plasma metanephrines was a highly sensitive (100%) and specific (96.7%) measure, yielding a negative predictive value of 100%. CONCLUSION: The satisfactory diagnostic efficacy of free plasma metanephrines allows their use as a single screening test in cases of suspected pheochromocytoma in the population with a low pretest probability.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Programas de Rastreamento/métodos , Metanefrina/sangue , Normetanefrina/sangue , Feocromocitoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/epidemiologia , Área Sob a Curva , Estudos Transversais , República Tcheca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/sangue , Feocromocitoma/epidemiologia , Valor Preditivo dos Testes
19.
Artigo em Inglês | MEDLINE | ID: mdl-15744360

RESUMO

Oxidative stress and especially its connection with many diseases has been discussed much recently. Among markers of oxidative stress there appear new and quite specific ones called advanced oxidation protein products (AOPPs). We tried to influence the level of AOPPs by an antioxidant therapy with N-acetylcysteine. Fourteen individuals with many cardiovascular risk factors were examined. All these patients were administered acetylcysteine (NAC) 600 mg/day orally during 20 days. Before starting the therapy we determined AOPP, albumin cobalt binding (ACB), glucose, creatinine, urea, ALT, AST, cholesterol, LDL, HDL and triglycerides values in peripheral venous blood in all individuals. After finishing our intervention we determined AOPP, ACB and glucose level again. Our results show a statistically significant decrease in AOPP levels after 20-day N-acetylcysteine therapy (medians, initially 82.2, at study end 74.3 umol/l, p = 0.039). We demonstrate a significant decrease in AOPP levels after 20-day N-acetylcysteine therapy in dose 600 mg/day.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Arteriosclerose/sangue , Biomarcadores/sangue , Proteínas Sanguíneas , Feminino , Sequestradores de Radicais Livres/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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