Search

BACKGROUND In advanced heart failure (HF), Levosimendan increases peak oxygen uptake (peakVO2). We investigated whether peakVO2 increase is linked to cardiovascular, respiratory or muscular performance changes. METHODS AND RESULTS Twenty patients hospitalized for advanced HF underwent, before and shortly after Levosimendan infusion, two different cardiopulmonary exercise tests (CPET): a) a personalized ramp protocol with repeated arterial blood gas analysis and standard spirometry including alveolar-capillary gas diffusion measurements at rest and at peak exercise, and b) a step incremental workload CPET with continuous near-infrared spectroscopy analysis and cardiac output (CO) assessment by bioelectrical impedance analysis. Levosimendan significantly reduced natriuretic peptides, improved peakVO2 (11.3 [IQR 10.1-12.8] to 12.6 [10.2-14.4] ml/Kg/min, p

Background: The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO2, VE/VCO2 slope, Na+, LVEF, MDRD and Hb. Methods: A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II - MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI 0, clinical deterioration). Results: The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, VE/VCO2 slope and blood Na+ concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters. Conclusions: This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF.

We investigated the synergistic effect of the new cone-bearing design of Jarvik 2000 (Jarvik Heart Inc., NY) together with a minimally-invasive approach to outcomes of LVAD patients.We retrospectively reviewed all patients from 5 institutions involved in the Jarvik 2000 Italian Registry, from October 2008 to October 2016. Patients were divided into three groups according to pump design and implantation technique: pin-bearing design and conventional approach (Group 1); cone-bearing and conventional approach (Group 2); cone-bearing and minimally-invasive implantation (Group 3).A total of 150 adult patients with end-stage heart failure were enrolled: 26 subjects in Group 1, 74 in Group 2, and 50 in Group 3. Nineteen patients (73%) in Group 1, 51 (69%) in Group 2, and 36 (72%) in Group 3 were discharged. During follow-up, 22 patients underwent transplantation, while in 3 patients the LVAD was explanted. The overall 1-year survival was 58 ± 10%, 64 ± 6%, and 74% ± 7% in Groups 1, 2, and 3, respectively (p = 0.034). The competing-risks-adjusted cumulative incidence rate for adverse events was 42.1 [27-62.7] per 100 patient-years in Group 1, 35.4 [25.3-48.2] in Group 2, and 22.1 [12.4-36.4] in Group 3 (p = 0.046 for Group 1 vs. 3).The association of the modern cone-bearing configuration of Jarvik 2000 and minimally invasive surgery improved survival and minimized the risk for cardiovascular events, as a result of combining technology and technique.

In heart failure, exercise – induced periodic breathing and end tidal carbon dioxide pressure value during the isocapnic buffering period are two features identified at cardiopulmonary exercise testing strictly related to sympathetic activation. In the present review we analysed the physiology behind periodic breathing and the isocapnic buffering period and present the relevant prognostic value of both periodic breathing and the presence/absence of the identifiable isocapnic buffering period.

To date, the pandemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has involved over 100 countries in a matter of weeks, and Italy suffers from almost 1/3 of the dead cases worldwide. In this report, we show the strategies adopted to face the emergency at Centro Cardiologico Monzino, a mono-specialist cardiology hospital sited in the region of Italy most affected by the pandemic, and specifically we describe how we have progressively modified in a few weeks the organization of our Heart Failure Unit in order to cope with the new COVID-19 outbreak. In fact, on the background of the pandemic, cardiovascular diseases still occur frequently in the general population, but we observed consistent reduction in hospital admissions for acute cardiovascular events and a dramatic increase of late presentation acute myocardial infarction. Despite a reduction of healthcare workers number, our ward has been rearranged in order to take care of both COVID-19 and cardiovascular patients. In particular according to a triple step procedure we divided admitted patients in confirmed, suspected and excluded cases (respectively allocated in “red”, “pink” and “green” separated areas). Due to the absence of definite guidelines, our aim was to describe our strategy in facing the current emergency, in order to reorganize our hospital in a dynamic and proactive manner. To quote the famous Italian writer Alessandro Manzoni ‘It is less bad to be agitated in doubt than to rest in error.’

Alveolar β2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar β2-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) β-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 ETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p

Heart transplantation represents the gold standard for end-stage heart failure. However, due to the increasing demand and the shortage of available organs, donor supply remains the main limitation. Marginal donor hearts in high-risk candidates who do not meet standard listing criteria are the only alternative when life expectancy is limited, but their use is still debated. Surgical correction of detected coronary lesions or valvular heart defects allows further enlargement of the number of available organs. In this article, we offer a literature review on this topic and report two marginal donor hearts with angiography evidence of coronary stenosis and preserved ventricular function, which underwent concomitant myocardial revascularization during heart implantation.

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.

AIMS Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population-based analysis, the long-term effects of MRA treatment in HFrEF patients. METHODS AND RESULTS We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan-Meier, compared by log-rank test and propensity score matching. At 10 years' follow-up, the MRA-untreated group had a significantly lower number of events than the MRA-treated group (P

Background Alveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary volume (Vcap) can be estimated by the multi-step Roughton and Foster (RF, original method from 1957) or the single-step NO–CO double diffusion technique (developed in the 1980s). The latter method implies inherent assumptions. We sought to determine which combination of the alveolar membrane diffusing capacity for nitric oxide (DMNO) to DMCO ratio, an specific conductance of the blood for NO (θNO) and CO (θCO) gave the lowest week-to-week variability in patients with heart failure. Methods 44 heart failure patients underwent DMCO and Vcap measurements on three occasions over a ten-week period using both RF and double dilution NO-CO techniques. Results When using the double diffusing method and applying θNO = infinity, the smallest week-to-week coefficient of variation for DMCO was 10 %. Conversely, the RF method derived DMCO had a much greater week-to-week variability (2x higher coefficient of variation) than the DMCO derived via the NO-CO double dilution technique. The DMCO derived from the double diffusion technique most closely matched the DMCO from the RF method when θNO = infinity and DMCO = DLNO/2.42. The Vcap measured week-to-week was unreliable regardless of the method or constants used. Conclusions In heart failure patients, the week-to-week DMCO variability was lowest when using the single-step NO-CO technique. DMCO obtained from double diffusion most closely matched the RF DMCO when DMCO/2.42 and θNO = infinity. Vcap estimation was unreliable with either method.

Aims Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-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 β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P 2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (

In chronic heart failure, minute ventilation (V′E) for a given carbon dioxide production (V′CO2) might be abnormally high during exercise due to increased dead space ventilation, lung stiffness, chemo- and metaboreflex sensitivity, early metabolic acidosis and abnormal pulmonary haemodynamics. The V′Eversus V′CO2 relationship, analysed either as ratio or as slope, enables us to evaluate the causes and entity of the V′E/perfusion mismatch. Moreover, the V′E axis intercept, i.e. when V′CO2 is extrapolated to 0, embeds information on exercise-induced dead space changes, while the analysis of end-tidal and arterial CO2 pressures provides knowledge about reflex activities. The V′Eversus V′CO2 relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. The V′Eversus V′CO2 slope is reported as an absolute number with a recognised cut-off prognostic value of 35, except for specific diseases such as hypertrophic cardiomyopathy and idiopathic cardiomyopathy, where a lower cut-off has been suggested. However, nowadays, it is more appropriate to report V′Eversus V′CO2 slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed in V′Eversus V′CO2 analysis in the presence of heart failure comorbidities. Finally, V′Eversus V′CO2 abnormalities are relevant targets for treatment in heart failure.

BACKGROUND Increasing left ventricular assist device (LVAD) pump speed according to the patient's activity is a fascinating hypothesis. This study analyzed the short-term effects of LVAD speed increase on cardiopulmonary exercise test (CPET) performance, muscle oxygenation (near-infrared spectroscopy), diffusion capacity of the lung for carbon monoxide (D lco ) and nitric oxide (D lno ), and sleep quality. METHODS We analyzed CPET, D lco and D lno , and sleep in 33 patients supported with the Jarvik 2000 (Jarvik Heart Inc., New York, NY). After a maximal CPET (n = 28), patients underwent 2 maximal CPETs with LVAD speed randomly set at 3 or increased from 3 to 5 during effort (n = 15). Then, at LVAD speed randomly set at 2 or 4, we performed (1) constant workload CPETs assessing O2 kinetics, cardiac output (CO), and muscle oxygenation (n = 15); (2) resting D lco and D lno (n = 18); and (3) nocturnal cardiorespiratory monitoring ( n = 29). RESULTS The progressive pump speed increase raised peak volume of oxygen consumption (12.5 ± 2.5 ml/min/kg vs 11.7 ± 2.8 ml/min/kg at speed 3; p = 0.001). During constant workload, from speed 2 to 4, CO increased (at rest: 3.18 ± 0.76 liters/min vs 3.69 ± 0.75 liters/min, p = 0.015; during exercise: 5.91 ± 1.31 liters/min vs 6.69 ± 0.99 liters/min, p = 0.014), and system efficiency (τ = 65.8 ± 15.1 seconds vs 49.9 ± 14.8 seconds, p = 0.002) and muscle oxygenation improved. At speed 4, D lco decreased, and obstructive apneas increased despite a significant apnea/hypopnea index and a reduction of central apneas. CONCLUSIONS Short-term LVAD speed increase improves exercise performance, CO, O2 kinetics, and muscle oxygenation. However, it deteriorates lung diffusion and increases obstructive apneas, likely due to an increase of intrathoracic fluids . Self-adjusting LVAD speed is a fascinating but possibly unsafe option, probably requiring a monitoring of intrathoracic fluids.

Recently, the number of patients with congenital heart diseases reaching adulthood has been progressively increasing in developed countries, and new issues are emerging: the evaluation of their capacity to cope with physical activity and whether this knowledge can be used to optimize medical management. A symptom-limited cardiopulmonary exercise test has proven to be an essential tool, because it can objectively evaluate the functional cardiovascular capacity of these patients, identify the pathological mechanisms of the defect (circulatory failure, shunts, and/or pulmonary hypertension), and help prescribe an individualized rehabilitation program when needed. The common findings on cardiopulmonary exercise testing in patients with congenital heart diseases are a reduced peak [Formula: see text]o2, an early anaerobic threshold, a blunted heart rate response, a reduced increase of Vt, and an increased [Formula: see text]e/[Formula: see text]co2. All these measures suggest common pathophysiological abnormalities: (1) a compromised exercise capacity from anomalies affecting the heart, vessels, lungs, or muscles; (2) chronotropic incompetence secondary to cardiac autonomic dysfunction or β-blockers and antiarrhythmic therapy; and (3) ventilatory inefficiency caused by left-heart failure with pulmonary congestion, pulmonary hypertension, pulmonary obstructive vascular disease, or cachexia. Most of these variables also have prognostic significance. For these patients, cardiopulmonary exercise testing allows evaluation and decisions affecting lifestyle and therapeutic interventions.

Backgrounds Peak exercise cardiac output (CO) increase is associated with an increase of peak oxygen uptake (VO 2 ), provided that arteriovenous O 2 difference [Δ(Ca−Cv)O 2 ] does not decrease. At anaerobic threshold, VO 2 , is related to CO. We tested the hypothesis that, in heart failure (HF) patients with left ventricular assistance device (LVAD), an acute increase of CO obtained through changes in LVAD pump speed is associated with peak exercise and anaerobic threshold VO 2 increase. Methods Fifteen of 20 patients bearing LVAD (Jarvik 2000) enrolled in the study successfully performed peak exercise evaluation. All patients had severe HF as shown by clinical evaluation, laboratory tests, echocardiography, spirometry with alveolar-capillary diffusion, and maximal cardiopulmonary exercise testing (CPET). CPETs with non-invasive CO measurements at rest and peak exercise were done on 2days at LVAD pump speed set randomly at 2 and 4. Results Increasing LVAD pump speed from 2 to 4 increased CO from 3.4±0.9 to 3.8±1.0L/min (ΔCO 0.4±0.6L/min, p =0.04) and from 5.3±1.3 to 5.9±1.4L/min (ΔCO 0.6±0.7L/min, p 2 increased from 788±169 to 841±152mL/min (ΔVO 2 52±76mL/min, p =0.01) and from 568±116 to 619±124mL/min (ΔVO 2 69±96mL/min, p =0.02) at peak exercise and at anaerobic threshold, respectively. Δ(Ca−Cv)O 2 did not change significantly, while ventilatory efficiency improved (VE/VCO 2 slope from 39.9±5.4 to 34.9±8.3, ΔVE/VCO 2 −5.0±6.4, p Conclusions In HF, an increase in CO with a higher LVAD pump speed is associated with increased peak VO 2 , postponed anaerobic threshold, and improved ventilatory efficiency.

Background: Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. Methods: Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (b11 g/dL), low (11–12 for females, 11–13 for males), normal (12–15 for females, 13–15 for males) and high (N15) Hb, respectively. Results: Median follow-up was 1363 days (606–1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR) = 0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire popula- tion. Considering Hb groups separately, peakVO2 (very low Hb HR = 0.549, low Hb HR = 0.613, normal Hb HR = 0.618, high Hb HR = 0.542) and LVEF (very low Hb HR = 0.49, low Hb HR = 0.692, normal Hb HR = 0.697, high Hb HR = 0.694) maintained their prognostic roles. High VE/VCO2 slope was associated with poor prognosis only in patients with low and normal Hb. Conclusions: Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their prognostic power also in HF patients with Hb b 11 g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.

Exercise oscillatory ventilation (EOV) is commonly observed during cardiopulmonary exercise testing (CPET) in heart failure (HF) patients and represents a derangement in the frequency and depth of ventilation during exercise with visual similarities to periodic breathing pattern, also common in HF. Its prevalence among different populations is not precisely accounted due to the lack of a common definition, despite its major prevalence being acknowledged among men. The physiology behind this phenomenon is complex and only partially defined and takes into account alterations in hemodynamics due to low cardiac output, alteration in chemoreceptor sensitivity, both peripheral and central, sympathetic activation, and altered inputs from muscle metaboreceptor.

BackgroundIn heart failure, lung diffusion is reduced, it correlates with prognosis and exercise capacity, and it is a therapy target.DesignDiffusion 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.MethodsWe 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.ResultsDLCO was 21.9 ± 4.8 ml/mmHg per min and 16.8 ± 5.1 i...

fraction. Rev Esp Cardiol 2013;66:261–8. [9] Herrmann HC, Pibarot P, Hueter I, et al. Predictors of mortality and outcomes of therapy in low-flow severe aortic stenosis: a Placement of Aortic Transcatheter Valves (PARTNER) Trial analysis. Circulation 2013;127:2316–26. [10] Ozkan A, Hachamovitch R, Kapadia SR, Tuzcu EM,Marwick TH. Impact of aortic valve replacement on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction. Circulation 2013;128(6):622–31.

Peak exercise cardiac output (CO) increase is associated with an increase of peak oxygen uptake (VOFifteen of 20 patients bearing LVAD (Jarvik 2000) enrolled in the study successfully performed peak exercise evaluation. All patients had severe HF as shown by clinical evaluation, laboratory tests, echocardiography, spirometry with alveolar-capillary diffusion, and maximal cardiopulmonary exercise testing (CPET). CPETs with non-invasive CO measurements at rest and peak exercise were done on 2days at LVAD pump speed set randomly at 2 and 4.Increasing LVAD pump speed from 2 to 4 increased CO from 3.4±0.9 to 3.8±1.0L/min (ΔCO 0.4±0.6L/min, p=0.04) and from 5.3±1.3 to 5.9±1.4L/min (ΔCO 0.6±0.7L/min, p0.01) at rest and peak exercise, respectively. Similarly, VOIn HF, an increase in CO with a higher LVAD pump speed is associated with increased peak VO

The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor’s protection of the lungs in HF during acute fluid overload. 100 HF patients (left ventricular ejection fraction ≤40 %) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500 cc saline. ACE I/D genotype prevalence was: DD = 28, ID =55 and II = 17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco −2.3 ± 1.3 vs. -0.8 ± 1.9 and −0.6 ± 1 mL/mmHg/min, p

Background In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption ( V ˙ o 2 ): 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 ˙ o 2 and ventilatory response ( V ˙ e/ V ˙ co 2 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 ˙ o 2 and V ˙ e/ V ˙ co 2 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 P = 0.667). After clinical profile harmonizing, female sex was predictive of HF at univariate analysis. Conclusions The low peak V ˙ o 2 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.

SUMMARY Aim: To assess the effect of chronotropic incompetence on functional capacity in chronic heart failure (CHF) patients, as evaluated as NYHA and peak oxygen consumption (pVO2), focusing on the presence and dose of β-blocker treatment. Methods: Nine hundred and sixty-seven consecutive CHF patients were evaluated, 328 of whom were discarded because they failed to meet the study criteria. Of the 639 analyzed, 90 were not treated with β-blockers whereas the other 549 were. The latter were further subdivided in high (n = 184) and low (n = 365) β-blockers daily dose group in accordance with an arbitrary cut-off of 25 mg for carvedilol and of 5 mg for bisoprolol. Failure to achieve 80% of the percentage of maximum age predicted peak heart rate (%Max PHR) or of HR reserve (%HRR) constituted chronotropic incompetence. Results: No differences were found in NYHA or pVO2 between patients with and without β-blockers and, similarly, between high and low β-blocker dose groups. Twenty and sixty-nine percent of not β-blocked patients showed chronotropic incompetence according to %Max PHR and %HRR, respectively, whereas this prevalence rose to 61% and 84% in those on β-blocker therapy. Patients taking β-blockers without chronotropic incompetence, as inferable from both %Max PHR and %HRR, showed higher NYHA and pVO2 regardless of drug dose, whereas, in not β-blocked patients, only %HRR revealed a difference in functional capacity. At multivariable analysis, HR increase during exercise (ΔHR) was the variable most strongly associated to pVO2 (β: 0.572; SE: 0.008; P < 0.0001) and NYHA class (β: −0.499; SE: 0.001; P < 0.0001). Conclusions: ΔHR is a powerful predictor of CHF severity regardless of the presence of β-blocker therapy and of β-blocker daily dose.

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/Vco(2)) relationship. The latter is an independent predictor of HF prognosis. beta-Blockers improve the prognosis of HF patients. We evaluated the effect on the efficiency of VE of a beta(1)-beta(2) unselective (carvedilol) versus a beta(1) selective (bisoprolol) beta-blocker.We analyzed consecutive maximal cardiopulmonary exercise tests performed on 572 clinically stable HF patients (New York Heart Association class I-III, left ventricle ejection fractionor =50%) categorized in 3 groups: 81 were not treated with beta-blocker, 304 were treated with carvedilol, and 187 were treated with bisoprolol. Clinical conditions were similar.The VE/Vco(2) 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 beta-blockers (31.6 +/- 0.7, P = .036). Maximum end-tidal CO(2) 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 beta-blockers (37.2 +/- 0.5 mm Hg, P = .001).Reduction of hyperventilation, with improvement of VE efficiency during exercise (reduction of VE/Vco(2) slope and increase of maximum end-tidal CO(2) pressure), is specific to carvedilol (beta(1)-beta(2) unselective blocker) and not to bisoprolol (beta(1)-selective blocker).

Introduction Erectile dysfunction (ED) is frequent in males with chronic heart failure (HF) with a severe impact on quality of life for many individuals. The correlation of ED with age and HF severity, comorbidity, and treatment is unclear. Aim We evaluated the correlation between ED and HF severity, treatment, and comorbidity. Methods One hundred one HF patients aged ≤70 years, with left ventricular ejection fraction ≤40%, and stable clinical condition took part in the study. We measured: (i) hemoglobin, glycemia, glicated hemoglobin, creatinine, cholesterol, thyroid-stimulating-hormone, C-reactive-protein, total/free testosterone; (ii) ED, depression, urological symptoms, and signs of low testosterone by means of questionnaires; and (iii) HF severity by means of echo, brain natriuretic peptide, and cardiopulmonary exercise test. Main Outcome Measures ED was measured by means of International Index of Erectile Function-5 questionnaire and its score was correlated with exercise cardiopulmonary test parameters, HF severity, treatment and HF comorbidities. Results ED prevalence was 69.3%, 81.1%, and 56% in total population and in patients with and without coronary artery lesions, respectively. ED was absent in 31 while it scored mild, mild to moderate, moderate and severe in 15, 18, 12, 25 individuals, respectively. Sexual activity requires, in the orgasmic phase, an oxygen consumption (VO 2 ) between 10 and 14 mL/min/kg. In none of the individuals with peakVO 2 2 between 10 and 14 mL/min/kg there was a normal or slightly reduced sexual performance. On monovariable analysis, several parameters were correlated with ED, but at multivariable analysis only age ( P = 0.002), hemoglobin ( P = 0.042), diabetes ( P = 0.040), and use of diuretics ( P = 0.052) remained so. Conclusions ED is frequent in HF. A normal or only slightly impaired sexual activity is possible with peakVO 2 > 10 mL/min/kg. On multivariable analysis, only age, diabetes, use of diuretics, and hemoglobin are related to ED. Apostolo A, Vignati C, Brusoni D, Cattadori G, Contini M, Veglia F, Magri D, Palermo P, Tedesco C, Doria E, Fiorentini C, Montorsi P, and Agostoni P. Erectile dysfunction in heart failure: Correlation with severity, exercise performance, comorbidities, and heart failure treatment. J Sex Med 2009;6:2795–2805.

BACKGROUND: Exertional oscillatory ventilation (EOV) in heart failure may potentiate the negative effects of low cardiac output and high ventilation on exercise performance. We hypothesized that the presence of EOV might, per se, influence exercise capacity as evaluated by maximal cardiopulmonary exercise test. METHODS AND RESULTS: We identified 78 severe chronic heart failure patient pairs with and without EOV. Patients were matched for sex, age and peak oxygen consumption (VO2). Patients with EOV showed, for the same peak VO2, a lower workload (WL) at peak (DeltaWatts=5.8+/-23.0, P=0.027), a less efficient ventilation (higher VE/VCO2 slope: 38.0+/-8.3 vs. 32.8+/-6.3, P

Background Periodic breathing (PB) in heart failure (HF) is attributed to many factors, including low cardiac output delaying the time it takes pulmonary venous blood to reach the central and peripheral chemoreceptors, low lung volume, lung congestion, augmented chemoreceptor sensitivity, and the narrow difference between eupneic carbon dioxide tension and apneic/hypoventilatory threshold. Methods and results We measured expired gases, ventilation, amplitude, and duration of PB in 23 patients with PB during progressive exercise tests done with 0 mL, 250 mL, or 500 mL of added dead space. Periodicity of PB remained constant despite heart rate, oxygen consumption, and minute ventilation increasing. Within each PB cycle, starting from the beginning of exercise, the largest (peak) tidal volume approached maximum observed tidal volume, while the smallest (nadir) tidal volume increased as exercise power output increased. PB ceased when nadir tidal volume reached peak tidal volume. End-tidal carbon dioxide increased with added dead space, and PB ceased progressively earlier during the exercise done with increased dead space. Conclusion Circulatory delay does not contribute to the PB observed in exercising HF patients. The pattern of gradually increasing nadir tidal volume during exercise and the effect of dead space on both PB ceasing and end-tidal carbon dioxide suggest that low tidal volume and carbon dioxide apnea threshold are important contributors to PB that occurs during exercise in HF.

In heart failure lung dysfunction is frequent and is greater the greater the heart failure severity. It can be evaluated in terms of lung mechanics and gas diffusion. Indeed heart-lung interaction is related to heart dimensions and lung fluid content; furthermore heart-lung interaction is influenced by the body position. Lung diffusion is also altered in patients with chronic heart failure, and a low gas diffusion is associated with a reduced performance. During exercise, heart-lung interaction becomes more evident. Heart failure patients show an abnormal hyperventilation due to a progressively increased respiratory rate, and a lower tidal volume; hyperventilation is due to different causes including enhanced responses from chemo- and metabolo-receptors, increased CO(2) production and increased dead space ventilation. Several drugs affect the ventilatory pattern in heart failure patients: ACE-inhibitors and anti-aldosteronic drugs improve lung diffusion and ventilatory efficiency during exercise; beta-blockers reduce exercise-induced hyperventilation. Furthermore, ultrafiltration improves lung mechanics, both at rest and during exercise, through body fluid content reduction.

Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) coexistence increases morbidity and mortality. The intercept of ventilation ( V ˙ E int ) on the V ˙ E vs. carbon dioxide production ( V ˙ CO 2 ) relationship during exercise has been found to vary in proportion with dead space (VD) in HF. Considering that increased VD is the key pathophysiological abnormality in COPD but a secondary finding in HF we hypothesized that a high V ˙ E int would be useful in suggesting COPD as HF co-morbidity. Our aim was to assess whether an elevated V ˙ E int suggests the presence of COPD in HF. Methods In a multicenter retrospective study, the V ˙ E– V ˙ CO 2 relationship was analyzed both as slope and intercept in HF (n=108), HF–COPD (n=106) and COPD (n=95). Patients with pulmonary arterial hypertension (PAH) (n=85) and healthy subjects (HF) (n=56) served as positive and negative controls relative to V ˙ E– V ˙ CO 2 abnormalities, respectively. Results Slope and V ˙ E int varied in opposite directions in all groups (p V ˙ E– V ˙ CO 2 slope highest and lowest in PAH and healthy subjects, respectively. No slope differences were observed among HF, HF–COPD and COPD (32±7, 31±7, and 31±6, respectively). V ˙ E int was higher in HF–COPD and COPD compared to HF, PAH and controls (4.8±2.4L/min, 5.9±3.0L/min, 3.0±2.6L/min, 2.3±3.3L/min and 3.9±2.5L/min, respectively; p V ˙ E int ≥4.07L/min identified patients with high probability of having COPD or HF–COPD (sensitivity of 71.6% and specificity of 72.0%). Conclusion These data provide novel evidence that a high V ˙ E int (≥4.07L/min) should be valued to suggest coexistent COPD in HF patients.

Central sleep apnea (CSA) is reported in advanced heart failure (HF) [(1)][1]. At least 3 factors have been suggested to play a pivotal role in CSA pathogenesis, specifically hyperventilation, which is the likely consequence of an enhanced stimulation of intrapulmonary receptors; low cardiac output

Background: Oxygen uptake at the anaerobic threshold (VO 2 AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO 2 AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. Design: We tested the prognostic role of VO 2 AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Methods: Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). Results: The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p=0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO 2 ) showed a prognostic capacity (C-index) similar to that obtained including VO 2 AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO 2 AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. Conclusions: VO 2 AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO 2 AT cut-off values between SR and AF HF patients should be adopted.

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

Periodic breathing (PB) during sleep and exercise in heart failure (HF) is related to respiratory acid-base status, CO2 chemosensitivity, and temporal dynamics of CO2 and O2 sensing. We studied inhaled CO2 and acetazolamide to alter these factors and reduce PB.We measured expired and arterial gases and PB amplitude and duration in 20 HF patients during exercise before and after acetazolamide given acutely (500 mg intravenously) and prolonged (24 hours, 2 g orally), and we performed overnight polysomnography. We studied CO2 inhalation (1%-2%) during constant workload exercise. PB disappeared in 19/20 and 2/7 patients during 2% and 1% CO2. No changes in cardiorespiratory parameters were observed after acute acetazolamide. With prolonged acetazolamide at rest: ventilation +2.04 ± 4.0 L/min (P = .001), tidal volume +0.11 ± 1.13 L (P = .003), respiratory rate +1.24 ± 4.63 breaths/min (NS), end-tidal PO2 +4.62 ± 2.43 mm Hg (P = .001), and end-tidal PCO2 -2.59 ± 9.7 mm Hg (P.001). At maximum exercise: Watts -10% (P.02), VO2 -61 ± 109 mL/min (P = .04) and VCO2 101 ± 151 mL/min (P.02). Among 20 patients, PB disappeared in 1 and 7 subjects after acute and prolonged acetazolamide, respectively. PB was present 80% ± 26, 65% ± 28, and 43% ± 39 of exercise time before and after acute and prolonged acetazolamide, respectively. Overnight apnea/hypopnea index decreased from 30.8 ± 83.8 to 21.1 ± 16.9 (P = .003).In HF, inhaled CO2 and acetazolamide reduce exercise PB with additional benefits of acetazolamide on sleep PB.

Lung function abnormalities both at rest and during exercise are frequently observed in patients with chronic heart failure, also in the absence of respiratory disease. Alterations of respiratory mechanics and of gas exchange capacity are strictly related to heart failure. Severe heart failure patients often show a restrictive respiratory pattern, secondary to heart enlargement and increased lung fluids, and impairment of alveolar-capillary gas diffusion, mainly due to an increased resistance to molecular diffusion across the alveolar capillary membrane. Reduced gas diffusion contributes to exercise intolerance and to a worse prognosis. Cardiopulmonary exercise test is considered the “gold standard” when studying the cardiovascular, pulmonary, and metabolic adaptations to exercise in cardiac patients. During exercise, hyperventilation and consequent reduction of ventilation efficiency are often observed in heart failure patients, resulting in an increased slope of ventilation/carbon dioxide (VE/VCO2) relationship. Ventilatory efficiency is as strong prognostic and an important stratification marker. This paper describes the pulmonary abnormalities at rest and during exercise in the patients with heart failure, highlighting the principal diagnostic tools for evaluation of lungs function, the possible pharmacological interventions, and the parameters that could be useful in prognostic assessment of heart failure patients.

Several β-blockers, with different pharmacological characteristics, are available for heart failure (HF) treatment. We compared Carvedilol (β1-β2-α-blocker), Bisoprolol (β1-blocker), and Nebivolol (β1-blocker, NO-releasing activity).Sixty-one moderate HF patients completed a cross-over randomized trial, receiving, for 2 months each, Carvedilol, Nebivolol, Bisoprolol (25.6 ± 12.6, 5.0 ± 2.4 and 5.0 ± 2.4 mg daily, respectively). At the end of each period, patients underwent: clinical evaluation, laboratory testing, echocardiography, spirometry (including total DLCO and membrane diffusion), O2/CO2 chemoreceptor sensitivity, constant workload, in normoxia and hypoxia (FiO2=16%), and maximal cardiopulmonary exercise test.No significant differences were observed for clinical evaluation (NYHA classification, Minnesota questionnaire), laboratory findings (including kidney function and BNP), echocardiography, and lung mechanics. DLCO was lower on Carvedilol (18.3 ± 4.8*mL/min/mmHg) compared to Nebivolol (19.9 ± 5.1) and Bisoprolol (20.0 ± 5.0) due to membrane diffusion 20% reduction (*=p0.0001). Constant workload exercise showed in hypoxia a faster VO2 kinetic and a lower ventilation with Carvedilol. Peripheral and central sensitivity to CO2 was lower in Carvedilol while response to hypoxia was higher in Bisoprolol. Ventilation efficiency (VE/VCO2 slope) was 26.9 ± 4.1* (Carvedilol), 28.8 ± 4.0 (Nebivolol), and 29.0 ± 4.4 (Bisoprolol). Peak VO2 was 15.8 ± 3.6*mL/kg/min (Carvedilol), 16.9 ± 4.1 (Nebivolol), and 16.9 ± 3.6 (Bisoprolol).β-Blockers differently affect several cardiopulmonary functions. Lung diffusion and exercise performance, the former likely due to lower interference with β2-mediated alveolar fluid clearance, were higher in Nebivolol and Bisoprolol. On the other hand, Carvedilol allowed a better ventilation efficiency during exercise, likely via a different chemoreceptor modulation. Results from this study represent the basis for identifying the best match between a specific β-blocker and a specific HF patient.

Objectives We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. Background HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. Methods Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4–5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. Results Six variables (hemoglobin, Na + , kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO 2 slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754–0.852) at 1year, 0.789 (0.750–0.828) at 2years, 0.762 (0.726–0.799) at 3years and 0.760 (0.724–0.796) at 4years. Conclusions This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC.

To assess the effect of chronotropic incompetence on functional capacity in chronic heart failure (CHF) patients, as evaluated as NYHA and peak oxygen consumption (pVO(2) ), focusing on the presence and dose of β-blocker treatment.Nine hundred and sixty-seven consecutive CHF patients were evaluated, 328 of whom were discarded because they failed to meet the study criteria. Of the 639 analyzed, 90 were not treated with β-blockers whereas the other 549 were. The latter were further subdivided in high (n = 184) and low (n = 365) β-blockers daily dose group in accordance with an arbitrary cut-off of 25 mg for carvedilol and of 5 mg for bisoprolol. Failure to achieve 80% of the percentage of maximum age predicted peak heart rate (%Max PHR) or of HR reserve (%HRR) constituted chronotropic incompetence.No differences were found in NYHA or pVO2 between patients with and without β-blockers and, similarly, between high and low β-blocker dose groups. Twenty and sixty-nine percent of not β-blocked patients showed chronotropic incompetence according to %Max PHR and %HRR, respectively, whereas this prevalence rose to 61% and 84% in those on β-blocker therapy. Patients taking β-blockers without chronotropic incompetence, as inferable from both %Max PHR and %HRR, showed higher NYHA and pVO2 regardless of drug dose, whereas, in not β-blocked patients, only %HRR revealed a difference in functional capacity. At multivariable analysis, HR increase during exercise (ΔHR) was the variable most strongly associated to pVO2 (β: 0.572; SE: 0.008; P0.0001) and NYHA class (β: -0.499; SE: 0.001; P0.0001).ΔHR is a powerful predictor of CHF severity regardless of the presence of β-blocker therapy and of β-blocker daily dose.

Background: The response to moderate exercise at altitude in heart failure (HF) is unknown. Methods and results: We evaluated 30 HF patients, (NYHA I-III, 25 M/5 F; 59 ± 10 years; LVEF = 39.6 ± 7.1%), in stable clinical conditions, treated with carvedilol at the maximal tolerated dose. We performed a maximal cardiopulmonary exercise test (CPET) with ramp protocol at sea level to evaluate patients’ performance and two moderate intensity constant workload CPETs (50% of peak workload) at sea level (normoxia) and simulated altitude (hypoxia). Oxygen uptake ([Formula: see text]) and heart rate (HR) on-kinetics at constant workload were assessed calculating the time constant (τ) with a monoexponential equation. [Formula: see text] and HR were higher in hypoxia (0.944 ± 0.233 vs 1.031 ± 0.264 l/min; 100 ± 23 vs 108 ± 22 bpm; p Conclusion: HF patients performing moderate exercise at 2000 m simulated altitude have 20% [Formula: see text] increase without trouble at the beginning of exercise when treated with carvedilol.

Anemia is frequent in chronic heart failure (HF). To calculate what change in peak oxygen uptake ( VO(2)) should be expected in the event of changes in hemoglobin concentration, we studied the correlation between peak VO(2) and hemoglobin concentration in a large HF population. We carried out retrospective analysis of all cardiopulmonary exercise tests (CPET) performed in our HF Clinic between June 2001 and March 2009 in HF patients who had a resting hemoglobin concentration measurement taken within 7 days of the CPET. We collected 967 CPETs, 704 tests were considered maximal and analyzed. We identified 181 patients (26%) as anemic. Peak VO(2) was lower (P < 0.001) in anemic patients (971 +/- 23 ml/min) compared with nonanemic (1243 +/- 18 ml/min). The slope of the VO(2) vs. hemoglobin ratio was 109 ml/min/g/dl at peak exercise. This correlation remained significant also when several confounding variables were analyzed by multivariate analysis. As an average, each gram of hemoglobin accounts, at peak exercise, for 109 ml/min change in VO(2) which is equivalent to 0.97 ml/min/kg. Therefore, in HF patients anemia treatment should increase VO(2) by 109 ml/min for each g/dl of hemoglobin increase.

Background— Surfactant protein type B (SPB) is needed for alveolar gas exchange. SPB is increased in the plasma of patients with heart failure (HF), with a concentration that is higher when HF severity is highest. The aim of this study was to evaluate the relationship between plasma SPB and both alveolar-capillary diffusion at rest and ventilation versus carbon dioxide production during exercise. Methods and Results— Eighty patients with chronic HF and 20 healthy controls were evaluated consecutively, but the required quality for procedures was only reached by 71 patients with HF and 19 healthy controls. Each subject underwent pulmonary function measurements, including lung diffusion for carbon monoxide and membrane diffusion capacity, and maximal cardiopulmonary exercise test. Plasma SPB was measured by immunoblotting. In patients with HF, SPB values were higher (4.5 [11.1] versus 1.6 [2.9], P =0.0006, median and 25th to 75th interquartile), whereas lung diffusion for carbon monoxide (19.7�4.5 versus 24.6�6.8 mL/mm Hg per min, P P P P P P P =0.004), and ventilation/carbon dioxide production slope (β, 0.25; SE, 0.026; P =0.034) were independently associated with SPB. Conclusion— Circulating plasma SPB levels are related to alveolar gas diffusion, overall exercise performance, and efficiency of ventilation showing a link between alveolar-capillary barrier damage, gas exchange abnormalities, and exercise performance in HF.

Erectile dysfunction (ED) is frequent in males with chronic heart failure (HF) with a severe impact on quality of life for many individuals. The correlation of ED with age and HF severity, comorbidity, and treatment is unclear.We evaluated the correlation between ED and HF severity, treatment, and comorbidity.One hundred one HF patients agedor =70 years, with left ventricular ejection fractionor =40%, and stable clinical condition took part in the study. We measured: (i) hemoglobin, glycemia, glicated hemoglobin, creatinine, cholesterol, thyroid-stimulating-hormone, C-reactive-protein, total/free testosterone; (ii) ED, depression, urological symptoms, and signs of low testosterone by means of questionnaires; and (iii) HF severity by means of echo, brain natriuretic peptide, and cardiopulmonary exercise test.ED was measured by means of International Index of Erectile Function-5 questionnaire and its score was correlated with exercise cardiopulmonary test parameters, HF severity, treatment and HF comorbidities.ED prevalence was 69.3%, 81.1%, and 56% in total population and in patients with and without coronary artery lesions, respectively. ED was absent in 31 while it scored mild, mild to moderate, moderate and severe in 15, 18, 12, 25 individuals, respectively. Sexual activity requires, in the orgasmic phase, an oxygen consumption (VO(2)) between 10 and 14 mL/min/kg. In none of the individuals with peak VO(2)10 mL/min/kg was sexual function normal or slightly impaired, while in 10/29 of patients with peak VO(2) between 10 and 14 mL/min/kg there was a normal or slightly reduced sexual performance. On monovariable analysis, several parameters were correlated with ED, but at multivariable analysis only age (P = 0.002), hemoglobin (P = 0.042), diabetes (P = 0.040), and use of diuretics (P = 0.052) remained so.ED is frequent in HF. A normal or only slightly impaired sexual activity is possible with peak VO(2)10 mL/min/kg. On multivariable analysis, only age, diabetes, use of diuretics, and hemoglobin are related to ED.

The present study was performed to evaluate how to assess cardiac resynchronization therapy (CRT) efficacy in chronic heart failure (CHF) through clinical, echocardiographic and exercise analysis. We analyzed 41 stable CHF (NYHA III) patients with: left bundle-branch-block, ejection fraction

In left ventricular failure (LVF) patients, brain natriuretic peptide (BNP), lung diffusion for carbon monoxide (DLCO), and alveolar-membrane conductance (DM) correlate with LVF severity and prognosis. The reduction of DLCO and DM during exercise reflects pulmonary edema formation.To evaluate, in LVF patients, the correlation between BNP and lung diffusion parameters at rest and during exercise, we studied 17 severe LVF patients, 13 moderate, and 10 normals measuring BNP and lung diffusion parameters before, at the end, and 1 hour after a 10-minute high-intensity constant-workload exercise. At rest, a significant correlation exists between BNP and lung diffusion parameters. Resting BNP, DLCO, and DM correlate with peak oxygen consumption (P.0001 for all analyses). With exercise, BNP increase is significant (severe LVF 180 +/- 49 pg/mL, moderate 68 +/- 58, normals 18 +/- 12); differently, only in severe LVF, with exercise, DLCO (-1.1 +/- 0.7 mL/mm Hg/min, P.0001) and DM (-6.4 +/- 2.8, P.0006) decrease. One hour after exercise, only in severe LVF, BNP is still higher than at rest, while DLCO, DM, and DM/Vc are lower. Significant correlations are observed between BNP and DM changes during exercise and recovery (P.0001) in severe LVF.In severe LVF, BNP changes during exercise correlate with simultaneous reductions in DM, suggesting that BNP increase and pulmonary edema formation could be related.

BACKGROUND Carvedilol is a beta-blocker with similar affinity for beta1- and beta2 receptors, while bisoprolol has higher beta1 affinity. The respiratory system is characterized by beta2-receptor prevalence. Airway beta receptors regulate bronchial tone and alveolar beta receptors regulate alveolar fluid re-absorption which influences gas diffusion. AIMS To compare the effects of carvedilol and bisoprolol on lung function in patients with chronic heart failure (CHF). METHODS AND RESULTS We performed a double-blind, cross-over study in 53 CHF patients. After 2 months of full dose treatment with either carvedilol or bisoprolol, we assessed lung function by salbutamol challenge, carbon monoxide lung diffusion (DLCO), including membrane conductance (DM), and gas exchange during exercise. FEV1 and FVC were similar; after salbutamol FEV1 was higher with bisoprolol (p

To the Editor: In heart failure (HF), measurement of cardiac output (CO) during exercise is important to define severity of the disease ([1][1]). Simultaneous measurements of oxygen consumption (Vo2) and CO during exercise allow calculation of arterio-venous oxygen difference [C(a-v)o2] ([2][2])

Aims: To evaluate whether carvedilol influences exercise hyperventilation and the ventilatory response to hypoxia in heart failure (HF). Methods and results: Fifteen HF patients participated to this double blind, randomised, placebo controlled, cross-over study. Patients were evaluated by quality of life questionnaire, echocardiography, pulmonary function and cardiopulmonary exercise tests (ramp and constant workload) both in normoxia (FiO2=21%) and hypoxia (FiO2=16%, equivalent to a simulated altitude of 2000m). Carvedilol improved clinical condition and reduced left ventricle size, but had no effect on lung mechanics. In normoxia during exercise, ventilation was lower, VCO2 unchanged and PaCO2 (constant workload) or PetCO2 (ramp) higher with carvedilol, exercise capacity was unchanged (peak workload 92±22 and 90±22W for placebo and carvedilol, respectively). Abnormal VE/VCO2 slope was reduced by carvedilol. Hypoxia increased ventilation but less with carvedilol; exercise capacity decreased to 87±21W (placebo) and to 80±11W (carvedilol, p