RESUMEN
AIMS: In chronic heart failure, proportional pulse pressure (PPP) is suggested as an estimate of cardiac index (CI). The association between CI and PPP in acute heart failure (AHF) has not been described. METHODS: This was examined using hemodynamic measurements (from a trial using serelaxin) in 63 stabilized AHF patients. RESULTS: Mean (SD) age was 68 (11), 74% male, mean (SD) ejection fraction (EF) was 33.4% (13.7), mean (SD) CI (L/min/m2) was 2.3 (0.6). CI correlated with PPP (Pearson R = 0.42; p < 0.0001) based on a linear mixed-effects model analysis of 171 pairs of measurements from 47 patients (out of 63) where CI and PPP were measured within 3 min of each other during. Serelaxin treatment did not modify the established correlation between CI and PPP. Time-weighted average CI correlated with time-weighted average PPP (Spearman Rank R = 0.35; p = 0.0051) over the -4 h to 24 h time interval. In a multivariable regression analysis, low PPP was an independent predictor of low CI (p < 0.0001). CONCLUSIONS: In patients with AHF after initial clinical stabilization, both baseline and post-baseline CI measurements are positively related to PPP. This was the most closely related non-invasive blood pressure variable to CI.
Asunto(s)
Presión Sanguínea , Insuficiencia Cardíaca/fisiopatología , Enfermedad Aguda , Anciano , Diástole , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Hipertensión/tratamiento farmacológico , Modelos Lineales , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Relaxina/uso terapéutico , Volumen Sistólico , SístoleRESUMEN
AIMS: The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF). METHODS AND RESULTS: This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) ≥ 18 mmHg, systolic blood pressure (BP) ≥ 115 mmHg, and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m(2) to serelaxin (n = 34) or placebo (n = 37) within 48 h of hospitalization. Co-primary endpoints were peak change from baseline in PCWP and cardiac index (CI) during the first 8 h of infusion. Among 63 patients eligible for haemodynamic analysis (serelaxin, n = 32; placebo, n = 31), those treated with serelaxin had a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: -2.44 mmHg, P = 0.004). Serelaxin showed no significant effect on the peak change in CI vs. placebo. Among secondary haemodynamic endpoints, a highly significant reduction in pulmonary artery pressure (PAP) was observed throughout the serelaxin infusion (largest difference in mean PAP vs. placebo: -5.17 mmHg at 4 h, P < 0.0001). Right atrial pressure, systemic/pulmonary vascular resistance, and systolic/diastolic BP decreased from baseline with serelaxin vs. placebo and treatment differences reached statistical significance at some time points. Serelaxin administration improved renal function and decreased N-terminal pro-brain natriuretic peptide levels vs. placebo. Treatment with serelaxin was well tolerated with no apparent safety concerns. CONCLUSION: The haemodynamic effects of serelaxin observed in the present study provide plausible mechanistic support for improvement in signs and symptoms of congestion observed with this agent in AHF patients. ClinicalTrials.gov identifier NCT01543854.
Asunto(s)
Cardiotónicos/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Relaxina/farmacología , Anciano , Análisis de Varianza , Presión Sanguínea/efectos de los fármacos , Cardiotónicos/administración & dosificación , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Insuficiencia Cardíaca/fisiopatología , Humanos , Infusiones Intravenosas , Masculino , Presión Esfenoidal Pulmonar/efectos de los fármacos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Relaxina/administración & dosificación , Resistencia Vascular/efectos de los fármacosRESUMEN
Invertebrates, tetrapod vertebrates, and fish might be expected to differ in their number of gene copies, possibly due the occurrence of genome duplication events during animal evolution. Reggie (flotillin) genes code for membrane-associated proteins involved in growth signaling in developing and regenerating axons. Until now, there appeared to be only two reggie genes in fruitflies, mammals, and fish. The aim of this research was to search for additional copies of reggie genes in fishes, since a genome duplication might have increased the gene copy number in this group. We report the presence of up to four distinct reggie genes (two reggie-1 and two reggie-2 genes) in the genomes of zebrafish and goldfish. Phylogenetic analyses show that the zebrafish and goldfish sequence pairs are orthologous, and that the additional copies could have arisen through a genome duplication in a common ancestor of bony fish. The presence of novel reggie mRNAs in fish embryos indicates that the newly discovered gene copies are transcribed and possibly expressed in the developing and regenerating nervous system. The intron/exon boundaries of the new fish genes characterized here correspond with those of human genes, both in location and phase. An evolutionary scenario for the evolution of reggie intron-exon structure, where loss of introns appears to be a distinctive trait in invertebrate reggie genes, is presented.