Association between multidrug resistance-1 C3435T gene polymorphism and right ventricular dysfunction in patients with chronic obstructive pulmonary disease: cross-sectional study

ABSTRACT BACKGROUND: Right ventricular (RV) dysfunction may develop over the course of chronic obstructive pulmonary disease (COPD) and is an important predictor of morbidity and mortality. Polymorphism of the multidrug resistance-1 (MDR-1) gene has been correlated with worse clinical findings among patients with COPD. Our aim here was to investigate the relationship between MDR-1 C3435T gene polymorphism and RV dysfunction in COPD patients. DESIGN AND SETTING: This was a cross-sectional study investigating the relationship between RV dysfunction and genetic defects in COPD patients. METHODS: Forty-one consecutive patients diagnosed with COPD and hospitalized due to acute exacerbation were enrolled. Polymorphism was analyzed using the strip assay technique. RV parameters were evaluated, and RV dysfunction was identified via transthoracic echocardiography. Patients were categorized into three groups according to gene polymorphism: MDR-1 CC (wild type, n = 9), MDR-1 CT (heterozygote mutant, n = 21) or MDR-1 TT (homozygote mutant, n = 11). RESULTS: The study included 14 males and 27 females (mean age 65 ± 11 years). The mean systolic pulmonary artery pressure was 31.4 ± 8 mmHg in the wild-type group, 42.2 ± 12 mmHg in the heterozygote mutant group and 46.5±14 mmHg in the homozygote mutant group (P = 0.027). Presence of RV dilatation was significantly different among the three groups (33%, 71%, and 100%, respectively; P = 0.005). In multiple logistic regression analysis, MDR-1 C3435T gene polymorphism (OR = 9.000, P = 0.019) was an independent predictor of RV dysfunction after adjustment for potential confounders. CONCLUSION: MDR-1 C3435T gene polymorphism was associated with RV dysfunction in patients with COPD.

Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting / Níveis elevados de gama glutamil transferase estão associados com a localização de embolia pulmonar aguda. Estudo transversal em ambiente hospitalar

ABSTRACT CONTEXT AND OBJECTIVE: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. DESIGN AND SETTING: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. METHODS : 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located), and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9); second group (thrombus in main pulmonary artery branches; n = 71); third group (thrombus in pulmonary artery segmental branches; n = 34); and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8). RESULTS : Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009) and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033) remained independently associated with proximally localized thrombus in pulmonary artery. CONCLUSIONS : The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.

RESUMO CONTEXTO E OBJETIVO : A localização da embolia está associada com os resultados clínicos e a gravidade da doença do embolismo pulmonar agudo (EPA). O nível de gama-glutamil transferase (GGT) aumenta em condições relacionadas com estresse oxidativo. Investigou-se se os níveis de GGT podem prever a localização do EPA. TIPO DE ESTUDO E LOCAL : Estudo observacional transversal na Universidade Cumhuriyet, Sivas, Turquia. MÉTODOS : Avaliamos 120 pacientes diagnosticados com EPA após a realização de angiografia pulmonar assistida por tomografia computadorizada. Eles foram divididos em dois grupos principais (localização proximal e distal) e depois em subgrupos de acordo com a localização do trombo da seguinte forma: primeiro grupo (trombo na artéria pulmonar [AP] principal, n = 9); segundo (trombo no ramo da AP principal; n = 71); terceiro grupo (trombo na segmentar da AP; n = 34); quarto grupo (trombo na subsegmentar da AP; n = 8). RESULTADOS : Na análise univariada, os níveis de GGT tiveram significado prognóstico em relação à admissão, pulsação arterial, saturação de oxigênio, dilatação do ventrículo direito/hipocinesia, pressão sistólica da artéria pulmonar (PSAP) e necessidade de ressuscitação cardiopulmonar. O modelo de regressão logística multivariada demonstrou que o nível de GGT na admissão (razão de possibilidades, OR: 1,044; 95% intervalo de confiança, CI: 1,011-1,079; P = 0,009) e PSAP (OR: 1,063, 95% CI: 1,005-1,124; P = 0,033) permaneceram independentemente associados com trombo localizado proximalmente na AP. CONCLUSÕES : Os resultados demonstraram associação significativa entre aumento da carga existente de embolia da AP e aumento dos níveis séricos da GGT.

Efeito do levosimendan em pacientes com insuficiência cardíaca sistólica severa e agravamento da função renal / Effect of levosimendan in patients with severe systolic heart failure and worsening renal function

FUNDAMENTO: O levosimendan, um sensibilizador de cálcio, aumenta a sensibilidade do coração para o cálcio, aumentando assim a contratilidade miocárdica, sem aumento do cálcio intracelular. Recentemente foi demonstrado que o levosimendan era benéfico na melhoria da função renal. No entanto, fica por determinar que o efeito benéfico esteja relacionado em forma diferencial ao status renal durante o evento-índice. OBJETIVO: O objetivo do presente estudo foi determinar se o levosimendan pode melhorar o resultado renal em pacientes com insuficiência cardíaca aguda descompensada com e sem agravamento da função renal. MÉTODOS: Quarenta e cinco pacientes consecutivos que tiveram uma taxa de filtração glomerular reduzida e pelo menos dois dados consecutivos quanto à função renal, antes da administração de levosimendan, foram incluídos no estudo. Os pacientes foram classificados em dois grupos, com e sem agravamento da função renal com base no aumento da creatinina sérica > 0,3 mg/dL. RESULTADOS: Uma melhoria significativa foi observada na função renal em pacientes com agravamento da função renal (creatinina sérica de 1,4 ± 0,16 a 1,21 ± 0,23 mg/dL, p = 0,001 e taxa de filtração glomerular de 48,9 ± 15 a 59,3 ± 21,8 mL/min/m², p = 0,011), apesar de que não houve melhoria significativa em aqueles sem agravamento da função renal (creatinina sérica de 1,29 ± 0,33 a 1,37 ± 0,66 mg/dL, p = 0,240 e taxa de filtração glomerular de 53,7 ± 17,6 a 52,9 ± 21,4 mL/min/m², p = 0,850). CONCLUSÃO: O levosimendan parece proporcionar um efeito de realce renal em pacientes com severa insuficiência cardíaca sistólica descompensada aguda e agravamento da função renal. Considerar esse efeito diferencial poderia contribuir a obter resultados renais benéficos. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

BACKGROUND: Levosimendan, a calcium sensitizer, increases the sensitivity of the heart to calcium, thus increasing myocardial contractility without a rise in intracellular calcium. It was recently shown that levosimendan is beneficial in improving renal function. However, it remains to be established that the beneficial effect is differentially related to renal status during index event. OBJECTIVE: The purpose of the current study was to determine whether levosimendan could improve renal outcome in acute decompensated heart failure patients with and without worsening renal function. METHODS: Forty-five consecutive patients who had a reduced glomerular filtration rate and had at least two consecutive data regarding renal function prior to administration of levosimendan were enrolled in the study. Patients were classified into two groups as those with and without worsening renal function based on an increase in serum creatinine >0.3 mg/dL. RESULTS: A significant improvement was noted in renal function in patients with worsening renal function (serum creatinine from 1.4±0.16 to 1.21±0.23 mg/dL, p=0.001 and glomerular filtration rate level from 48.9±15 to 59.3±21.8 mL/min/m², p=0.011), while there was no significant improvement in those without worsening renal function (serum creatinine from 1.29±0.33 to 1.37±0.66 mg/dL, p=0.240 and glomerular filtration rate level from 53.7±17.6 to 52.9±21.4 mL/min/m², p=0.850). CONCLUSION: Levosimendan appears to provide a renal-enhancing effect in patients with severe, acute decompensated systolic heart failure and worsening renal function. Consideration of this differential effect might help obtain beneficial renal outcomes. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).