Aims
Peak exercise oxygen uptake (VO2) and cardiac output (CO) are strong prognostic indexes in heart failure (HF) but unrelated to real‐life physical activity, which is associated to submaximal ...effort.
Methods and results
We analysed maximal cardiopulmonary exercise test with rest, mid‐exercise, and peak exercise non‐invasive CO measurements (inert gas rebreathing) of 231 HF patients and 265 healthy volunteers. HF patients were grouped according to exercise capacity (peak VO2 < 50% and ≥50% pred, Groups 1 and 2). To account for observed differences, data regarding VO2, CO, stroke volume (SV), and artero‐venous O2 content difference ΔC(a‐v)O2 were adjusted by age, gender, and body mass index. A multiple regression analysis was performed to predict peak VO2 from mid‐exercise cardiopulmonary exercise test and CO parameters among HF patients. Rest VO2 was lower in HF compared with healthy subjects; meanwhile, Group 1 patients had the lowest CO and highest ΔC(a‐v)O2. At mid‐exercise, Group 1 patients achieved a lower VO2, CO, and SV 0.69 (interquartile range 0.57–0.80) L/min; 5.59 (4.83–6.67) L/min; 62 (51–73) mL than Group 2 0.94 (0.83–1.1) L/min; 7.6 (6.56–9.01) L/min; 77 (66–92) mL and healthy subjects 1.15 (0.93–1.30) L/min; 9.33 (8.07–10.81) L/min; 87 (77–102) mL. Rest to mid‐exercise SV increase was lower in Group 1 than Group 2 (P = 0.001) and healthy subjects (P < 0.001). At mid‐exercise, ΔC(a‐v)O2 was higher in Group 2 13.6 (11.8–15.4) mL/100 mL vs. healthy patients 11.6 (10.4–13.2) mL/100 mL (P = 0.002) but not different from Group 1 13.6 (12.0–14.9) mL/100 mL. At peak exercise, Group 1 patients achieved a lower VO2, CO, and SV than Group 2 and healthy subjects. ΔC(a‐v)O2 was the highest in Group 2. At multivariate analysis, a model comprising mid‐exercise VO2, carbon dioxide production (VCO2), CO, haemoglobin, and weight predicted peak VO2, P < 0.001. Mid‐exercise VO2 and CO, haemoglobin, and weight added statistically significantly to the prediction, P < 0.050.
Conclusions
Mid‐exercise VO2 and CO portend peak exercise values and identify severe HF patients. Their evaluation could be clinically useful.
Abstract Background In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption ( V ˙ o2 ): this raises doubt about the accuracy of risk assessment by ...cardiopulmonary exercise testing (CPET) in women. Accordingly, we aimed to check (1) whether the predictive role of well-known CPET risk indexes, ie, peak V ˙ o2 and ventilatory response ( V ˙ e / V ˙ co2 slope), is sex independent and (2) if sex-related characteristics that impact outcome in HF should be considered as associations that may confound the effect of sex on survival. Methods The study population consisted of 2985 patients with HF, 498 (17%) of whom were women, from the multicentre Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI): the end point was cardiovascular death within a 3-year period. Results During the follow-up, 305 (12%) men and 39 (8%) women ( P = 0.005) died, and female sex was linked to better survival on univariate analysis ( P = 0.008) and independent of peak V ˙ o2 and V ˙ e / V ˙ co2 slope on multivariate analysis. According to propensity score matching for female sex to exclude a sex selection bias and sample discrepancy, 498 men were selected: the standardized percentage bias ranged from 20.8 ( P < 0.0001) to 3.3 ( P = 0.667). After clinical profile harmonizing, female sex was predictive of HF at univariate analysis. Conclusions The low peak V ˙ o2 and female association with better outcome in HF might be counterfeit: the female prognostic advantage is lost when sex-specific differences are correctly taken into account with propensity score matching, suggesting that for an effective and efficient HF model, adjustment must be made for sex-related characteristics.
Identifying functional partners for protein/protein interactions can be a difficult challenge. We proposed the use of the operon structure of the Caenorhabditis elegans genome as a “new gene-finding ...tool” (Eichmüller, S., Vezzoli, V., Bazzini, C., Ritter, M., Fürst, J., Jakab, M., Ravasio, A., Chwatal, S., Dossena, S., Bottà, G., Meyer, G., Maier, B., Valenti, G., Lang, F., and Paulmichl, M. (2004) J. Biol. Chem. 279, 7136–7146) that could be functionally translated to the human system. Here we show the validity of this approach by studying the predicted functional interaction between ICln and HSPC038. In C. elegans, the gene encoding for the ICln homolog (icln-1) is embedded in an operon with two other genes, Nx (the human homolog of Nx is HSPC038) and Ny. ICln is a highly conserved, ubiquitously expressed multifunctional protein that plays a critical role in the regulatory volume decrease after cell swelling. Following hypotonic stress, ICln translocates from the cytosol to the plasma membrane, where it has been proposed to participate in the activation of the swelling-induced chloride current (IClswell). Here we show that the interaction between human ICln and HSPC038 plays a role in volume regulation after cell swelling and that HSPC038 acts as an escort, directing ICln to the cell membrane after cell swelling and facilitating the activation of IClswell. Assessment of the NMR structure of HSPC038 showed the presence of a zinc finger motif. Moreover, NMR and additional biochemical techniques enabled us to identify the putative ICln/HSPC038 interacting sites, thereby explaining the functional interaction of both proteins on a molecular level.
Background: The operon structure of the C. elegans genome was used to identify functional interaction partners for the chloride channel ICln.
Results: Human ICln and HSPC038 functionally interact, and this interaction between the two proteins was also identified on a molecular level.
Conclusion: The functional interaction between ICln and HSPC038 modulates the regulation of the cellular volume.
Significance: The operon structure of the C. elegans genome can be used to identify unknown interaction partners including those of membrane proteins, and the summarized experiments provide further insight into the interactome of the connector hub ICln.
Background:In patients with chronic heart failure (HF) the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score, is a predictor of cardiovascular death and urgent heart transplantation. We ...investigated the relationship between age, exercise tolerance and the prognostic value of the MECKI score.Methods and Results:We analyzed data from 3,794 patients with chronic systolic HF. The primary endpoint was a composite of cardiovascular death and urgent heart transplantation. Older patients had higher prevalence of comorbidities and lower exercise performance compared with younger subjects (peak V̇O2, 925 vs. 1,351 L/min; P<0.0001; V̇E/V̇CO2slope, 33.2 vs. 28.3; P>0.0001). The rate of the primary endpoint was 19% in the highest age quartile and 14% in the lowest quartile. At multivariable analysis, the independent predictors of the primary endpoint were left ventricular ejection fraction (LVEF), eGFR, peak V̇O2, serum Na+and the use of β-blockers in patients aged ≥70 years, and LVEF, eGFR and peak V̇O2in younger subjects. The MECKI risk score increased across age subgroups, but on receiver operating characteristic curve analysis its prognostic power was similar in both patients aged ≥70 and <70 years.Conclusions:Older patients with HF are a high-risk population with lower exercise performance. The MECKI score increased according to age and maintained its prognostic value also in older patients. (Circ J 2015; 79: 2608–2615)
Background Hyperventilation and consequent reduction of ventilation (VE) efficiency are frequently observed during exercise in heart failure (HF) patients, resulting in an increased slope of ...VE/carbon dioxide (VE/V co2 ) relationship. The latter is an independent predictor of HF prognosis. β-Blockers improve the prognosis of HF patients. We evaluated the effect on the efficiency of VE of a β1 -β2 unselective (carvedilol) versus a β1 selective (bisoprolol) β-blocker. Methods We analyzed consecutive maximal cardiopulmonary exercise tests performed on 572 clinically stable HF patients (New York Heart Association class I-III, left ventricle ejection fraction ≤50%) categorized in 3 groups: 81 were not treated with β-blocker, 304 were treated with carvedilol, and 187 were treated with bisoprolol. Clinical conditions were similar. Results The VE/V co2 slope was lower in carvedilol- compared with bisoprolol-treated patients (29.7 ± 0.4 vs 31.6 ± 0.5, P = .023, peak oxygen consumption adjusted) and with patients not receiving β-blockers (31.6 ± 0.7, P = .036). Maximum end-tidal CO2 pressure during the isocapnic buffering period was higher in patients treated with carvedilol (39.0 ± 0.3 mm Hg) than with bisoprolol (37.2 ± 0.4 mm Hg, P < .001) and in patients not receiving β-blockers (37.2 ± 0.5 mm Hg, P = .001). Conclusions Reduction of hyperventilation, with improvement of VE efficiency during exercise (reduction of VE/V co2 slope and increase of maximum end-tidal CO2 pressure), is specific to carvedilol (β1 -β2 unselective blocker) and not to bisoprolol (β1 -selective blocker).
Abstract Receptor-of-Advanced-Glycation-End-products (RAGE) and Surfactant-Protein-type-B (SPB) are reported as lung injury markers. Unlike SPB, RAGE is secreted by several tissues, so that RAGE ...specificity as lung injury marker is questionable. We measured SPB and RAGE in 19 patients undergoing major vascular abdominal surgery. SPB and RAGE were measured before mechanical ventilation ( T0 ), at 1st ( T1 ), 2nd ( T2 ) and, when present, 3rd ( T3 ) hour of mechanical ventilation, and 1 h after extubation ( TPOST ). Last data during mechanical ventilation, either T2 or T3 , are reported as TEND . SPB and RAGE values were normalized for total protein (SPBN and RAGEN ). SPBN and RAGEN increments from T0 to TEND were 56.2 39.1 ng/mg (mean 75–25 percentile) and 10.67.1 pg/mg, respectively. SPB values increased progressively during mechanical ventilation, whereas RAGE values increased at T1 but not thereafter. SPBN increase ( TEND − T0 ), but not RAGEN , was related to ΔPaO2 /FiO2 changes during mechanical ventilation ( r = 0.575, p = 0.01). Plasma RAGEN and SPBN kinetics in patients undergoing major vascular surgery are different.
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