Variability in pulmonary diffusing capacity in heart failure.

BACKGROUND: As pulmonary diffusing capacity is related to mortality risk and prognosis in patients with heart failure (HF), it is measured frequently. As such, it would be essential to know the week-to-week variability (reproducibility) of pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO). This variability would let clinicians understand what a clinically measurable change in DLCO and DLNO would be in these patients. METHODS: On three different days spanning over ten weeks, 40 H F patients underwent testing for DLCO and DLNO. DLCO was determined after a 4 s and 10 s breath-hold maneuver, while DLNO was determined after a 4 s breath-hold maneuver. RESULTS: Forty heart failure patients (66 ± 10 years; BMI = 28.4 ± 4.6 kg∙m-2; 28 males), that were referred to our clinic were able to complete the protocol. DLCO (4 s breath-hold) and DLNO (4 s breath-hold) were 79 ± 19 % and 59 ± 14 % predicted, respectively. Fifty percent of patients (n = 20) were below the lower limit of normal (LLN, below the 5th percentile) for predicted DLCO (4 s), while 78 % of patients (n = 31) were below the LLN for predicted DLNO. All 16 patients that were below the LLN for DLCO were also below the LLN for DLNO. Over a ten week period, the reproducibility of DLNO (4 s) DLCO (4 s) and DLCO (10 s) was 18.9, 8.2, and 5.9 mL min mmHg-1, respectively. CONCLUSIONS: The week-to-week fluctuation in DLNO (4 s), as a percentage, is less than DLCO (4 s) in patients with HF. The reproducibility of DLNO in patients with HF is like that of healthy subjects.

Effects of ß2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective ß-blockers: a randomized trial.

Alveolar ß2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar ß2-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) ß-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal PETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.

Do rebreathing manoeuvres for non-invasive measurement of cardiac output during maximum exercise test alter the main cardiopulmonary parameters?

BACKGROUND: Inert gas rebreathing has been recently described as an emergent reliable non-invasive method for cardiac output determination during exercise, allowing a relevant improvement of cardiopulmonary exercise test clinical relevance. For cardiac output measurements by inert gas rebreathing, specific respiratory manoeuvres are needed which might affect pivotal cardiopulmonary exercise test parameters, such as exercise tolerance, oxygen uptake and ventilation vs carbon dioxide output (VE/VCO2) relationship slope. METHOD: We retrospectively analysed cardiopulmonary exercise testing of 181 heart failure patients who underwent both cardiopulmonary exercise testing and cardiopulmonary exercise test+cardiac output within two months (average 16 ± 15 days). All patients were in stable clinical conditions (New York Heart Association I-III) and on optimal medical therapy. RESULTS: The majority of patients were in New York Heart Association Class I and II (78.8%), with a mean left ventricular ejection fraction of 31 ± 10%. No difference was found between the two tests in oxygen uptake at peak exercise (1101 (interquartile range 870-1418) ml/min at cardiopulmonary exercise test vs 1103 (844-1389) at cardiopulmonary exercise test-cardiac output) and at anaerobic threshold. However, anaerobic threshold and peak heart rate, peak workload (75 (58-101) watts and 64 (42-90), p < 0.01) and carbon dioxide output were significantly higher at cardiopulmonary exercise testing than at cardiopulmonary exercise test+cardiac output, whereas VE/VCO2 slope was higher at cardiopulmonary exercise test+cardiac output (30 (27-35) vs 33 (28-37), p < 0.01). CONCLUSION: The similar anaerobic threshold and peak oxygen uptake in the two tests with a lower peak workload and higher VE/VCO2 slope at cardiopulmonary exercise test+cardiac output suggest a higher respiratory work and consequent demand for respiratory muscle blood flow secondary to the ventilatory manoeuvres. Accordingly, VE/VCO2 slope and peak workload must be evaluated with caution during cardiopulmonary exercise test+cardiac output.

Surfactant proteins changes after acute hemodynamic improvement in patients with advanced chronic heart failure treated with Levosimendan.

Alveolar-capillary membrane evaluated by carbon monoxide diffusion (DLCO) plays an important role in heart failure (HF). Surfactant Proteins (SPs) have also been suggested as a worthwhile marker. In HF, Levosimendan improves pulmonary hemodynamics and reduces lung fluids but associated SPs and DLCO changes are unknown. Sixty-five advanced HF patients underwent spirometry, cardiopulmonary exercise test (CPET) and SPs determination before and after Levosimendan. Levosimendan caused natriuretic peptide-B (BNP) reduction, peakVO2 increase and VE/VCO2 slope reduction. Spirometry improved but DLCO did not. SP-A, SP-D and immature SP-B reduced (73.7 ±â€¯25.3 vs. 66.3 ±â€¯22.7 ng/mL*, 247 ±â€¯121 vs. 223 ±â€¯110 ng/mL*, 39.4 ±â€¯18.7 vs. 34.4 ±â€¯17.9AU*, respectively); while mature SP-B increased (424 ±â€¯218 vs. 461 ±â€¯243 ng/mL, * = p < 0.001). Spirometry, BNP and CPET changes suggest hemodynamic improvement and lung fluid reduction. SP-A, SP-D and immature SP-B reduction indicates a reduction of inflammatory stress; conversely mature SP-B increase suggests alveolar cell function restoration. In conclusion, acute lung fluid reduction is associated with SPs but not DLCO changes. SPs are fast responders to alveolar-capillary membrane condition changes.

Exercise performance, haemodynamics, and respiratory pattern do not identify heart failure patients who end exercise with dyspnoea from those with fatigue.

AIMS: The two main symptoms referred by chronic heart failure (HF) patients as the causes of exercise termination during maximal cardiopulmonary exercise testing (CPET) are muscular fatigue and dyspnoea. So far, a physiological explanation why some HF patients end exercise because of dyspnoea and others because of fatigue is not available. We assessed whether patients referring dyspnoea or muscular fatigue may be distinguished by different ventilator or haemodynamic behaviours during exercise. METHODS AND RESULTS: We analysed exercise data of 170 consecutive HF patients with reduced left ventricular ejection fraction in stable clinical condition. All patients underwent maximal CPET and a second maximal CPET with measurement of cardiac output by inert gas rebreathing at peak exercise. Thirty-eight (age 65.0 ± 11.1 years) and 132 (65.1 ± 11.4 years) patients terminated CPET because of dyspnoea and fatigue, respectively. Haemodynamic and cardiorespiratory parameters were the same in fatigue and dyspnoea patients. VO2 was 10.4 ± 3.2 and 10.5 ± 3.3 mL/min/kg at the anaerobic threshold and 15.5 ± 4.8 and 15.4 ± 4.3 at peak, in fatigue and dyspnoea patients, respectively. In fatigue and dyspnoea patients, peak heart rate was 110 ± 22 and 114 ± 22 beats/min, and VE/VCO2 and VO2 /work relationship slopes were 31.2 ± 6.8 and 30.6 ± 8.2 and 10.6 ± 4.2 and 11.4 ± 5.5 L/min/W, respectively. Peak cardiac output was 6.68 ± 2.51 and 6.21 ± 2.55 L/min (P = NS for all). CONCLUSIONS: In chronic HF patients in stable clinical condition, fatigue and dyspnoea as reasons of exercise termination do not highlight different ventilatory or haemodynamic patterns during effort.

Prognostic role of ß-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database.

AIMS: The use of ß-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared ß-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of ß-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of ß-selectivity and dosage regimens. METHODS AND RESULTS: In 5242 HFrEF patients, we investigated the role of: (i) ß-blocker treatment vs. non-ß-blocker treatment, (ii) ß1-/ß2-receptor-blockers vs. ß1-selective blockers, and (iii) daily ß-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on ß-blockers, while 807 (13.2%) were not. At 5 years, ß-blocker-patients showed a better outcome than non-ß-blocker-subjects [hazard ratio (HR) 0.48, P < 0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the ß1-/ß2-receptor-blocker (n = 2219) vs. ß1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5-25 mg, n = 1431) and low dose (<12.5 mg, n = 1960) (HR 1.97, P < 0.001; HR 1.95, P = 0.001, respectively), with no differences between the last two groups (HR 0.84, P = ns). CONCLUSION: In a large population of chronic HFrEF patients, ß-blockers were associated with a more favourable prognosis without any difference between ß1- and ß2-receptor-blockers vs. ß1-selective blockers. A better outcome was observed in subjects receiving a high daily dose.