Alessandra Magini

Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia

To evaluate whether carvedilol influences exercise hyperventilation and the ventilatory response to hypoxia in heart failure (HF).

Alveolar–capillary membrane diffusion measurement by nitric oxide inhalation in heart failure

Background In heart failure, lung diffusion is reduced, it correlates with prognosis and exercise capacity, and it is a therapy target. Design Diffusion is measured as CO total diffusion (DLCO), which has two components: membrane diffusion (Dm) and capillary volume, the latter related to CO and O2 competition for hemoglobin. DLCO needs to be corrected for hemoglobin. Diffusion can also be measured with NO (DLNO), which has a very high affinity for hemoglobin, and thus, the resistance of hemoglobin being trivial, it directly represents Dm. Therefore, Dm is directly calculated from DLNO through a correction factor. DLNO has never been measured in heart failure. The study aims at determining, in heart failure, DLNO, Dm correction factor, and whether DmNO provides Dm estimates comparable to DmCO. Methods We measured DLCO, DmCO by multi-maneuver Roughton–Forster method, and DLCO and DLNO by single-breath maneuver in 50 heart failure and 50 healthy subjects. Results DLCO was 21.9 ± 4.8 ml/mmHg per min and 16.8 ± 5.1 in healthy subjects and heart failure subjects, respectively (p < 0.001). DLNO was 88.6 ± 20.5 ml/mmHg per min and 72.5 ± 22.3, respectively (p < 0.001). The correction factors to obtain Dm from DLNO were 2.68 (entire population), 2.63 (healthy subjects) and 2.75 (heart failure subjects). DmCO and DmNO were 34.7 ± 10.9 ml/mmHg per min and 33.8 ± 7.6 in healthy subjects and 25.9 ± 2.0 and 26.4 ± 8.1 in heart failure subjects. Conclusions DLNO and DmNO measurements are feasible in heart failure. DmCO and DmNO provide comparable results. The correction factor to calculate Dm from DLNO in heart failure is 2.75, which is little different from the 2.63 value we observed in healthy subjects.

Exercise capacity in patients with β-thalassaemia intermedia

Thalassaemia intermedia patients can suffer fatigue and exercise capacity reduction, possibly because of anaemia, deconditioning and lack of exercise‐induced haemoconcentration. We studied 21 β‐thalassaemia intermedia patients, 10 splenectomised (group A) and 11 not splenectomised (group B). Patients were evaluated by cardiopulmonary exercise test with blood sampling for haemoglobin and plasma protein measurements at rest and peak. During exercise, an isolated increase of haemoglobin suggested spleen contraction while a parallel increase of haemoglobin and proteins suggested fluid filtration through capillary wall. Groups were homogeneous for age and gender. Peak oxygen consumption (VO2) was 22·5 ± 4·4 ml/min/kg (51 ± 14%) and 24·3 ± 7·0 (53 ± 12%) in groups A and B respectively [not significant (NS)]. At rest, haemoglobin was 8·8 g/dl in both groups. Exercise‐induced increment was 0·4 ± 0·2 and 1·0 ± 0·4 g/dl (P < 0·001) for haemoglobin and 4·0 ± 3·0 and 5·0 ± 4·0 g/l (NS) for proteins, in groups A and B respectively. Anaemia was the major cause of peak VO2 reduction (1097 ± 260 ml/min). However, anaemia did not explain the entire exercise capacity reduction, suggesting the presence of muscular deconditioning. Exercise capacity is reduced in β‐thalassaemia intermedia because of anaemia and muscular deconditioning. Spleen contraction does not significantly influence exercise capacity although exercise‐induced haemoconcentration was greater in patients with spleen.

ST2 and B-type natriuretic peptide kinetics during exercise in severe heart failure: ST2 and B-type natriuretic peptide kinetics during exercise in severe heart failure

In chronic heart failure (HF), risk stratification is one of the most challenging issues, with a plethora of biomarkers available for this purpose. The key role is played by B-type natriuretic peptide (BNP) and/or its amino-terminal fragment NT-proBNP.1 Accordingly, all new biomarkers should be compared with BNP and/or should be characterized by prognostic capability in selected HF populations. Soluble ST2 has recently been introduced among the new biomarkers. The presence of high levels of ST2 is related to the severity of HF and to an increased risk of complications, such as arrhythmias, acute decompensation, and death, independently of natriuretic peptides.2 Indeed, a prognostic role of ST2 has been suggested in low-risk populations,3 in patients with chronic,4 advanced, and acute2 HF. Regardless, at present, the most defined role of ST2 is to provide a prognostic value additive to that of NT-proBNP within a multiparametric prognostic approach.5 The changes in ST2 in response to an acute haemodynamic event are presently unknown, and specifically it is unknown whether ST2 response to an acute haemodynamic event has the same magnitude and time frame of that reported for BNP. Indeed, in patients with severe HF, BNP increases even during a 10 min maximal exercise, probably mirroring acute pulmonary haemodynamic worsening.6 We studied 30 (67±10 years, 28 male) consecutive patients with chronic severe HF (left ventricular ejection fraction 29± 9%) who belonged to an HF population regularly followed at our HF unit. Inclusion criteria were peak oxygen uptake (VO2) <12 mL/kg/min, optimized HF therapy, stable clinical conditions, left ventricular ejection fraction (echocardiography) <45%, and capability to perform spirometry and lung diffusion test. The locally appointed ethics committee approved the research protocol (R115/14-CCM), and informed consent was obtained from all patients. Patients underwent a 10 min cycleergometer ramp cardiopulmonary exercise test protocol. Immediately before exercise and at peak exercise, venous blood was sampled for BNP and ST2 determination. At the same time, lung diffusion (DLCO) and its two components membrane diffusion (DM) and capillary volume (Vcap) were measured. DLCO was measured by the single-breath constant expiratory flow technique (Sensor Medics 2200, Yorba Linda, CA, USA). DLCO subcomponents, Vcap and DM, were calculated applying the Roughton and Forster method. Soluble ST2 levels were assessed using a highly sensitive sandwich monoclonal immunoassay (Presage® ST2 Assay, Critical Diagnostics, San Diego, CA, USA). BNP was measured using the chemiluminescent microparticle immunoassay on the Architect i2000 analyser (Abbott Diagnostics, Abbott Park, IL, USA). Data confirmed severe exercise limitation, since peak VO2 was 855± 224 mL/min, equivalent to 10.8±1.6 mL/kg/min and to 45± 8% of the predicted value, VO2 at anaerobic threshold was 8.0±1.4 mL/kg/min, and ventilation/carbon dioxide production relationship slope was 38±10. DLCO, BNP and ST2 at rest and peak exercise are reported in Table 1. BNP (rest–peak +15±16%, P< 0.05), but not ST2 (rest–peak 1±12%), significantly increased at peak exercise, showing that a transitory haemodynamic impairment

Reply to commentary on: Confusion in reporting pulmonary diffusion capacity for nitric oxide and the alveolar-capillary membrane conductance for nitric oxide:

We read with interest the commentary by Gerald Zavorsky and Colin Borland on our paper on lung diffusion for nitric oxide (DLNO) vs lung diffusion for carbon monoxide (DLCO) in normal subjects and in patients with heart failure. Both authors are worldwide recognised experts. We are therefore indebted with them for the time and thought they gave to our work. The criticisms that they raise are both methodological and physiological. Indeed, DLNO measurement for clinical purposes has been introduced only a few years ago since the commercial apparatus has been available. Studies about simultaneous DLNO/DLCO evaluation have been conducted with different analysers and different NO concentrations so the method is still far from being standardised. However, we recognise that our DLNO values in normal subjects, obtained in a sizeable number of subjects, are lower than those previously reported by Zavorsky et al. In any case the apparatus we used (Jaeger/Vyasis PFT Masterscreen) was calibrated for gas analysis using automated procedures and the linearity of analysers was factory checked. The formula used is: