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OBJECTIVE: To evaluate the role of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and a cardiovascular (CV) risk score named FRESCO for predicting anthracycline-induced cardiotoxicity (AIC) in diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 130 consecutive DLBCL patients treated in first-line with anthracycline-containing immunochemotherapy. Competitive risk between NT-proBNP, FRESCO, and time to AIC was considered. RESULTS: Cumulative incidence of AIC was 12.2% and 17.5% at 1 and 5 years, respectively. Median time to development cardiotoxicity was 6.4 months, with half of the cases showing heart failure and the other half silent AIC. Both NT-proBNP levels and FRESCO score were independently associated with higher risk of AIC (P = 0.001 and P = 0.03, respectively). Patients with NT-proBNP ≥600 pg/mL or those with FRESCO ≥4.5% had 3.97 or 2.54 times higher risk of AIC than those with lower values (P = 0.001 and P = 0.048, respectively). According to the previous cutoffs, three groups of patients with a significantly different risk of AIC could be identified (P < 0.0001). CONCLUSIONS: Doxorubicin-containing chemotherapy is associated with increased risk of silent and overt AIC. Baseline NT-proBNP levels and FRESCO CV risk score are accurate predictors of AIC and can identify groups of patients at different risk, in which personalized cardiologic evaluation should be offered.
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Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Linfoma Difuso de Grandes Células B/complicações , Idoso , Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Cardiotoxicidade , Feminino , Cardiopatias/sangue , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , EspanhaRESUMO
BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the prevalence and clinical value of the pathological ankle-brachial index (ABI) in asymptomatic aortic stenosis (AS) patients. METHODS: This prospective study included 203 asymptomatic AS patients, with a mean follow up of 18 ± 10.6 months. Six-minute walk tests (6MWT) and ABI measurements were performed when patients were included in the study. Study events were defined as death, hospital admission due to related symptoms, or a need for surgery. RESULTS: A total of 198 patients (95 females, 103 males; mean age 74.6 ± 9.5 years) completed the study. An abnormal ABI was found in 35.8%. Mean (± SD) values were: peak velocity Vmax 4.1 ± 0.8 m/s; maximum/mean gradient 70.5 ± 25.1/43.3 ± 16.3 mmHg; aortic valve area 0.8 ± 0.7 cm2; indexed aortic valve area 0.4 ± 0.1 cm2/m2. A pathological ABI was associated with diabetes (p = 0.01), previous peripheral vascular disease (p = 0.04) and previous stroke (p = 0.04). In multivariate analyses, diabetes was an independent factor related to pathological ABI (relative risk 1.71, 95% CI 1.22-2.19). Patients with a pathological ABI walked less in the 6MWT (263.9 m versus 328.3; p = 0.002), but did not present a worse prognosis at follow up (p = NS). CONCLUSION: Among asymptomatic AS patients, 35.8% had an abnormal ABI and this was related to previous diabetes. These patients walked less in the 6MWT but did not have a worse prognosis at follow up.
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Índice Tornozelo-Braço , Estenose da Valva Aórtica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/mortalidade , Doenças Assintomáticas , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Estudos ProspectivosRESUMO
Anderson-Fabry disease (FD), an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-Gal A) activity, is associated with cardiac manifestations including arrhythmias, valvular abnormalities, and cardiomyopathy. Early initiation of enzyme replacement therapy (ERT) may have the potential to delay the underlying clinical outcomes in patients with FD. Clinical electrocardiogram (ECG) and echocardiography were used to characterize the cardiomyopathy. Diagnosis of FD was performed by measuring the α-Gal A activity in plasma and mutation analysis by direct sequencing using capillary electrophoresis. We identified four adult hemizygous male patients with cardiomyopathy and other symptoms related to FD; two of them were monozygotic twins. In all cases, ECG and echocardiography showed severe left ventricular (LV) hypertrophy. Some years later, all patients showed typical symptoms of FD, including angiokeratomas and neurological, renal, gastrointestinal, and ocular involvement. A deficiency of α-Gal A activity and point mutations in exon 5 of the GLA gene were detected in all patients. ERT (agalsidase-alfa) was administered every other week as a 0.2 mg/kg intravenous infusion over 40 min. In conclusion, these findings highlight the importance of screening middle-aged patients with LV hypertrophy for the early detection of FD, particularly in direct-line relatives such as twins.
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Cardiomiopatias/genética , Códon sem Sentido/genética , Doenças em Gêmeos/genética , Doença de Fabry/genética , Hipertrofia Ventricular Esquerda/genética , Mutação de Sentido Incorreto/genética , Adulto , Eletrocardiografia , Genótipo , Hemizigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Gêmeos Dizigóticos , Gêmeos MonozigóticosRESUMO
The aim of this work was to study the association of potential biomarkers with fast aortic stenosis (AS) progression. Patients with moderate-to-severe AS were classified as very fast progressors (VFP) if exhibited an annualized change in peak velocity (aΔVmax) ≥0.45m/s/year and/or in aortic valve area (aΔAVA) ≥-0.2cm2/year. Respective cut-off values of ≥0.3m/s/year and ≥-0.1cm2/year defined fast progressors (FP), whereas the remaining patients were non-fast progressors (non-FP). Baseline markers of lipid metabolism, inflammation, and cardiac overload were determined. Two hundred and nine patients (97 non-FP, 38 FP, and 74 VFP) were included. PCSK9 levels were significantly associated with VFP (OR 1.014 [95%CI 1.005-1.024], for every 10 ng/mL), as were active smoking (OR 3.48) and body mass index (BMI, OR 1.09), with an AUC of 0.704 for the model. PCSK9 levels, active smoking, and BMI were associated with very fast AS progression in our series, suggesting that inflammation and calcification participate in disease progression.
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Estenose da Valva Aórtica , Pró-Proteína Convertase 9 , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/diagnóstico por imagem , Biomarcadores , Progressão da Doença , Humanos , InflamaçãoRESUMO
INTRODUCTION AND OBJECTIVES: Identifying biomarkers of subclinical atrial fibrillation (AF) is of most interest in patients with cryptogenic stroke (CrS). We sought to evaluate the circulating microRNA (miRNA) profile of patients with CrS and AF compared with those in persistent sinus rhythm. METHODS: Among 64 consecutive patients with CrS under continuous monitoring by a predischarge insertable monitor, 18 patients (9 with AF and 9 in persistent sinus rhythm) were selected for high-throughput determination of 754 miRNAs. Nine patients with concomitant stroke and AF were also screened to improve the yield of miRNA selection. Differentially expressed miRNAs were replicated in an independent cohort (n=46). Biological markers were stratified by the median and included in logistic regression analyses to evaluate their association with AF at 6 and 12 months. RESULTS: Eight miRNAs were differentially expressed between patients with and without AF. In the replication cohort, miR-1-3p, a gene regulator involved in cardiac arrhythmogenesis, was the only miRNA to remain significantly higher in patients with CrS and AF vs those in sinus rhythm and showed a modest association with AF burden. High (= above the median) miR-1-3p plasma values, together with a low left atrial ejection fraction, were independently associated with the presence of AF at 6 and 12 months. CONCLUSIONS: In this cohort, plasma levels of miR-1-3p were elevated in CrS patients with subsequent AF. Our results preliminarily suggest that miR-1-3p could be a novel biomarker that, together with clinical parameters, could help identify patients with CrS and a high risk of occult AF.
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Fibrilação Atrial , MicroRNA Circulante , AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/genética , Biomarcadores , Átrios do Coração , Humanos , MicroRNAs/genética , Acidente Vascular Cerebral/complicaçõesRESUMO
Silent atrial fibrillation (AF) may be the cause of some cryptogenic strokes (CrS). The aim of the study was to analyse atrial size and function by speckle tracking echocardiography in CrS patients to detect atrial disease. Patients admitted to the hospital due to CrS were included prospectively. Echocardiogram analysis included left atrial ejection fraction (LAEF) and atrial strain. Insertable cardiac monitor was implanted, and AF was defined as an episode of ≥1 min in the first year after stroke. Left atrial enlargement was defined as indexed volume > 34 mL/m2. Seventy-five consecutive patients were included, aged 76 ± 9 years (arterial hypertension 75%). AF was diagnosed in 49% of cases. The AF group had higher atrial volume and worse atrial function: peak atrial longitudinal strain (PALs) 19.6 ± 5.7% vs. 29.5 ± 7.2%, peak atrial contraction strain (PACs) 8.9 ± 3.9% vs. 16.5 ± 6%, LAEF 46.8 ± 11.5% vs. 60.6 ± 5.2%; p < 0.001. AF was diagnosed in 20 of 53 patients with non-enlarged atrium, and in 18 of them, atrial dysfunction was present. The multivariate logistic regression analysis demonstrated an independent association between detection of AF and atrial volume, LAEF, and strain. Cut-off values were obtained: LAEF < 55%, PALs < 21.4%, and PACs < 12.9%. In conclusion, speckle tracking echocardiography in CrS patients improves silent atrial disease diagnosis, with or without atrial enlargement.
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INTRODUCTION AND OBJECTIVES: Bioresorbable vascular scaffolds (BVS) have the potential to restore vasomotion but the clinical implications are unknown. We sought to evaluate angina and ischemia in the long-term in patients treated with BVS and metallic drug-eluting stents (mDES). METHODS: Multicenter study including patients with 24 ± 6 months of uneventful follow-up, in which stress echocardiography was performed and functional status was assessed by the Seattle Angina Questionnaire (SAQ). The primary endpoint was a positive result in stress echocardiography. RESULTS: The study included 102 patients treated with BVS and 106 with mDES. There were no differences in the patients' baseline characteristics. Recurrent angina was found in 18 patients (17.6%) in the BVS group vs 25 (23.5%) in the mDES group (P = .37), but SAQ results were significantly better in the BVS group (angina frequency 96.0 ± 8.0 vs 89.2 ± 29.7; P = .02). Stress echocardiography was positive in 11/92 (11.9%) of BVS patients vs 9/96 (9.4%) of mDES patients in the (P = .71) and angina was induced in 2/102 (1.9%) vs 7/106 (6.6%) (P = .18), respectively, but exercise performance was better in the BVS group even in those with positive tests (exercise duration 9.0 ± 2.0minutes vs 7.7 ± 1.8minutes; P = .02). A propensity score matching analysis yielded similar results. CONCLUSIONS: The primary endpoint was similar in both groups. In addition, recurrent angina was similar in patients with BVS and mDES. The better functional status, assessed by means of SAQ and exercise performance, detected in patients receiving BVS should be confirmed in further studies.
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Angina Pectoris/terapia , Stents Farmacológicos , Ecocardiografia sob Estresse/métodos , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/instrumentação , Alicerces Teciduais , Implantes Absorvíveis , Idoso , Angina Pectoris/diagnóstico , Estudos de Coortes , Eletrocardiografia/métodos , Everolimo/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Intervenção Coronária Percutânea/métodos , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Centros de Atenção Terciária , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To develop and validate a short questionnaire to estimate physical activity (PA) practice and sedentary behavior for the adult population. METHODS: The short questionnaire was developed using data from a cross-sectional population-based survey (n = 6352) that included the Minnesota leisure-time PA questionnaire. Activities that explained a significant proportion of the variability of population PA practice were identified. Validation of the short questionnaire included a cross-sectional component to assess validity with respect to the data collected by accelerometers and a longitudinal component to assess reliability and sensitivity to detect changes (n = 114, aged 35 to 74 years). RESULTS: Six types of activities that accounted for 87% of population variability in PA estimated with the Minnesota questionnaire were selected. The short questionnaire estimates energy expenditure in total PA and by intensity (light, moderate, vigorous), and includes 2 questions about sedentary behavior and a question about occupational PA. The short questionnaire showed high reliability, with intraclass correlation coefficients ranging between 0.79 to 0.95. The Spearman correlation coefficients between estimated energy expenditure obtained with the questionnaire and the number of steps detected by the accelerometer were as follows: 0.36 for total PA, 0.40 for moderate intensity, and 0.26 for vigorous intensity. The questionnaire was sensitive to detect changes in moderate and vigorous PA (correlation coefficients ranging from 0.26 to 0.34). CONCLUSION: The REGICOR short questionnaire is reliable, valid, and sensitive to detect changes in moderate and vigorous PA. This questionnaire could be used in daily clinical practice and epidemiological studies.
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Exercício Físico/fisiologia , Atividade Motora/fisiologia , Inquéritos e Questionários/normas , Adulto , Idoso , Estudos Transversais , Metabolismo Energético , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Tissue Doppler imaging (TDI) and N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP) provides useful non-invasive information about left ventricle filling pressures and both have demonstrated to be a prognostic marker in some valve disease as aortic stenosis (AS). OBJECTIVES: To assess the clinical value of combined TDI and NT-proBNP information in asymptomatic AS patients. MATERIAL AND METHODS: Prospective study of 350 initially asymptomatic moderate to severe AS patients with: Mean aortic valve area 0.8 (0.3) cm2, mean gradient 45(13) mmHg, ejection fraction 61 (9) %. Mean age: 74.6 (4.3) years. In all patients were determined NT-proBNP in the serum and TDI parameters the lateral mitral annulus. We considered clinical event the admission in the hospital due to symptoms related to AS (angina, heart failure or syncope) as well as surgical treatment or mortality. RESULTS: After a mean follow-up of 29 (10) months, 165 (47%) patients suffered some clinical event. In order to predict clinical events, Bootstrap analysis determined the best cut-point value: E/E' ratio higher than 13 and NT-proBNP higher than 515pg/mL. E/E' ratio provides more specificity (78.9% vs 55.9%) and NT-proBNP provides more sensitivity (76.6% vs 43.7%). Combined use of both parameters provides the best prognostic information (sensitivity 75.6%, specificity 67.2%, negative predictive value 82.1%, positive predictive value 57.5%, accuracy 71.4%). CONCLUSION: Combined use of TDI and natriuretic peptides information provides incremental prognostic value and is a useful tool to predict the prognosis in asymptomatic AS patients.
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Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia Doppler , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Estenose da Valva Aórtica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Análise de SobrevidaRESUMO
Cardiovascular disease, closely related to an early appearance of hypertension, is the most common mortality cause among autosomal dominant polycystic kidney disease patients (ADPKD). The development of hypertension is related to an increase in renal volume. Whether the increasing in the renal volume before the onset of hypertension leads to a major cardiovascular risk in ADPKD patients remains unknown.Observational and cross-sectional study of 62 normotensive ADPKD patients with normal renal function and a group of 28 healthy controls. Renal volume, blood pressure, and renal (urinary albumin excretion), blood vessels (carotid intima media thickness and carotid-femoral pulse wave velocity), and cardiac (left ventricular mass index and diastolic dysfunction parameters) asymptomatic organ damage were determined and were considered as continuous variables. Correlations between renal volume and the other parameters were studied in the ADPKD population, and results were compared with the control group. Blood pressure values and asymptomatic organ damage were used to assess the cardiovascular risk according to renal volume tertiles.Even though in the normotensive range, ADPKD patients show higher blood pressure and major asymptomatic organ damage than healthy controls. Asymptomatic organ damage is not only related to blood pressure level but also to renal volume. Multivariate regression analysis shows that microalbuminuria is only associated with height adjusted renal volume (htTKV). An htTKV above 480âmL/m represents a 10 times higher prevalence of microalbuminuria (4.8% vs 50%, Pâ<â0.001). Normotensive ADPKD patients from the 2nd tertile renal volume group (htTKVâ>â336âmL/m) show higher urinary albumin excretion, but the 3rd tertile htTKV (htTKVâ>â469âmL/m) group shows the worst cardiovascular risk profile.Normotensive ADPKD patients show in the early stages of the disease with slight increase in renal volume, higher cardiovascular risk than healthy controls. An htTKV above 468âmL/m is associated with the greatest increase in cardiovascular risk of normotensive ADPKD patients with normal renal function. Early strategies to slow the progression of the cardiovascular risk of these patients might be beneficial in their long-term cardiovascular survival.
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Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Hipertensão/etiologia , Rim/patologia , Rim Policístico Autossômico Dominante/complicações , Adulto , Fatores Etários , Análise de Variância , Pressão Sanguínea/fisiologia , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tamanho do Órgão , Rim Policístico Autossômico Dominante/diagnóstico , Prognóstico , Curva ROC , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estatísticas não ParamétricasRESUMO
The objective of the study is to investigate the impact of anemia (defined as hemoglobin concentration of <12 g/dl in women and 13 g/dl in men) on prognosis and to study the effect of recovery from anemia on echocardiographic and clinical parameters in patients with aortic stenosis (AS). This was a prospective study in 315 patients with moderate or severe AS. Patients with anemia received oral iron (ferrous sulfate with mucoproteose, 160 mg iron/day) and erythropoietin, if needed, or intravenous iron, if necessary. The following tests were performed before and after normalization of hemoglobin values: echocardiogram, 6-minute walk test, N-terminal B-type natriuretic peptide, and measures of depression, cognitive impairment, and dependence. Patient mean age was 74 years (SD 9). Mean follow-up was 25 months (SD 8). Anemia prevalence in the overall group was 22% (n = 70). Patients who are anemic had a higher rate of complications at follow-up (mortality, hospital admission, or need for valve procedure; 80% vs 62%, p = 0.009). In total, 89% of patients recovered from anemia, with a mean time to recovery of 4.6 weeks (SD 1.4). Improvements were observed on echocardiographic parameters of peak velocity (4.1 to 3.7 m/s, p = 0.02) and mean gradient (44 to 35 mm Hg, p = 0.02). Performance on the 6-minute walk test improved from 235 to 303 m (p <0.001). Median N-terminal B-type natriuretic peptide value decreased from 612 to 189 pg/dl (p <0.001). In conclusion, patients with AS and anemia have a worse prognosis than those without anemia. Resolution of anemia is associated with improvements in echocardiographic parameters and functional status, suggesting that treatment of iron deficiency is a relevant option in the management of patients with AS, particularly in nonoperable cases.
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Anemia/tratamento farmacológico , Estenose da Valva Aórtica/cirurgia , Ecocardiografia , Eritropoetina/administração & dosagem , Ferro/administração & dosagem , Volume Sistólico , Função Ventricular Esquerda/fisiologia , Idoso , Anemia/complicações , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/complicações , Quimioterapia Combinada , Teste de Esforço , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
INTRODUCTION AND OBJECTIVES: Our objective was to assess the prognostic value of NT-proBNP in patients with asymptomatic moderate/severe aortic stenosis and to validate an adapted Monin score using natriuretic peptide levels in our setting. METHODS: Prospective study of 237 patients with degenerative asymptomatic moderate/severe aortic stenosis. NT-proBNP was determined in all patients, who were then followed up clinically. The adapted Monin score was defined as follows: (peak velocity [m/s]×2)+(logn NT-proBNP×1.5)(+1.5 if woman). A clinical event was defined as surgery, hospital admission due to angina, heart failure or syncope, or death. RESULTS: A total of 51% were women, and the mean age was 74 years. Mean (SD) echocardiographic values were as follows: peak velocity 4.14 (0.87) m/s; mean gradient, 43.2 (16.0) mmHg; aortic valve area, 0.87 (0.72) cm(2), and aortic valve area index, 0.49 (0.14) cm(2)/m(2). The median NT-pro-BNP value was 490.0 [198.0-1312.0] pg/mL. There were 153 events during follow-up (median 18 months). The optimum NT-proBNP cut-point was 515 pg/mL, giving event-free survival rates at 1 and 2 years of 93% and 57%, respectively, in patients with NT-proBNP <515 pg/mL compared with 50% and 31% in those with NT-proBNP >515 pg/mL. Patients were divided into quartiles based on the Monin score. Event-free survival at 1 and 2 years was 87% and 79% in the first quartile, compared with 45% and 28% in the fourth quartile, respectively. CONCLUSIONS: NT-proBNP determination provides prognostic information in patients with asymptomatic moderate/severe aortic stenosis. The adapted Monin score is useful in our setting and allows a more precise prognosis than does the use of NT-proBNP alone.