Combined aerobic/resistance/inspiratory muscle training as the 'optimum' exercise programme for patients with chronic heart failure: ARISTOS-HF randomized clinical trial.

AIMS: An 'optimum' universally agreed exercise programme for heart failure (HF) patients has not been found. ARISTOS-HF randomized clinical trial evaluates whether combined aerobic training (AT)/resistance training (RT)/inspiratory muscle training (IMT) (ARIS) is superior to AT/RT, AT/IMT or AT in improving aerobic capacity, left ventricular dimensions, and secondary functional outcomes. METHODS AND RESULTS: Eighty-eight patients of New York Heart Association II-III, left ventricular ejection fraction ≤ 35% were randomized to an ARIS, AT/RT, AT/IMT, or AT group, exercising 3 times/week, 180 min/week for 12 weeks. Pre- and post-training, peakVO2 was evaluated with cardiopulmonary exercise testing, left ventricular dimensions using echocardiography, walking distance with the 6-min walk test (6MWT), quality of life by the Minnesota Living with HF Questionnaire (MLwHFQ), while a programme preference survey (PPS) was used. Seventy-four patients of [mean 95% (confidence interval, CI)] age 66.1 (64.3-67.9) years and peakVO2 17.3 (16.4-18.2) mL/kg/min were finally analysed. Between-group analysis showed a trend for increased peakVO2 (mL/kg/min) [mean contrasts (95% CI)] in the ARIS group [ARIS vs. AT/RT 1.71 (0.163-3.25)(.), vs. AT/IMT 1.50 (0.0152-2.99)(.), vs. AT 1.38 (-0.142 to 2.9)(.)], additional benefits in circulatory power (mL/kg/min⋅mmHg) [ARIS vs. AT/RT 376 (60.7-690)*, vs. AT/IMT 423 (121-725)*, vs. AT 345 (35.4-656)*], left ventricular end-systolic diameter (mm) [ARIS vs. AT/RT -2.11 (-3.65 to (-0.561))*, vs. AT -2.47 (-4.01 to (-0.929))**], 6MWT (m) [ARIS vs. AT/IMT 45.6 (18.3-72.9)**, vs. AT 55.2 (27.6-82.7)****], MLwHFQ [ARIS vs. AT/RT -7.79 (-11 to (-4.62))****, vs. AT -8.96 (-12.1 to (-5.84))****], and in PPS score [mean (95% CI)] [ARIS, 4.8 (4.7-5) vs. AT, 4.4 (4.2-4.7)*] [(.) P ≤ 0.1; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001]. CONCLUSION: ARISTOS-HF trial recommends exercise training for 180 min/week and supports the prescription of the ARIS training regime for HF patients (Clinical Trial Registration: http://www.clinicaltrials.gov. ARISTOS-HF Clinical Trial number, NCT03013270).

Inspiratory work capacity is more severely depressed than inspiratory muscle strength in patients with heart failure: Novel applications for inspiratory muscle training.

BACKGROUND: We hypothesized that the ability to sustain maximal inspiratory pressure (SPImax) over time as a measure of work capacity may be more severely affected than inspiratory muscle strength (PImax) in patients with heart failure (HF). METHODS: We retrospectively investigated eighty patients with HF, NYHA II/III/ ambulatoryIV and a (mean±SD) LVEF 27±8%, and compared them to 25 healthy subjects (HS). During a maximal inspiratory manoeuvre from residual volume (RV) to total lung capacity, PImax was measured as the maximum mouth pressure at RV, inspiratory contraction time (ICT) as the time from RV to end of inspiration and SPImax as the area under a pressure-time curve using an electronic pressure manometer with designed-purpose software (Trainair(®), Project Electronics Ltd., London, UK). Exercise capacity was assessed with cardiopulmonary exercise testing and the 6-minute walk test (6MWT). RESULTS: Patients achieved a (mean±SD) peak VO2=15.7±3.4ml/kg/min and 6MWT=338±88m. PImax, ICT and SPImax were reduced in HF pts at 75%***, 61%*** and 52%*** of HS, and correlated with NYHA (r=-0.485***), (r=-0.507**), (r=-0.500***), peakVO2 (r=0.501***), (r=0.655***), (r=0.508***) and 6MWT (r=0.477***), (r=0.345**), (r=0.530***), respectively (*p<0.05, **p<0.01, ***p<0.001). CONCLUSION: PImax, ICT and SPImax were impaired in HF patients compared to HS and may be important determinants of exercise capacity. SPImax was severely depressed even in patients with relatively preserved PImax and should be considered as an additional target index for inspiratory muscle training. Equations are provided to predict SPImax in relation to age and exercise capacity in HF.

Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure: The Vent-HeFT trial: a European prospective multicentre randomized trial.

AIMS: Vent-HeFT is a multicentre randomized trial designed to investigate the potential additive benefits of inspiratory muscle training (IMT) on aerobic training (AT) in patients with chronic heart failure (CHF). METHODS AND RESULTS: Forty-three CHF patients with a mean age of 58 ± 12 years, peak oxygen consumption (peak VO2 ) 17.9 ± 5 mL/kg/min, and LVEF 29.5 ± 5% were randomized to an AT/IMT group (n = 21) or to an AT/SHAM group (n = 22) in a 12-week exercise programme. AT involved 45 min of ergometer training at 70-80% of maximum heart rate, three times a week for both groups. In the AT/IMT group, IMT was performed at 60% of sustained maximal inspiratory pressure (SPImax ) while in the AT/SHAM group it was performed at 10% of SPImax , using a computer biofeedback trainer for 30 min, three times a week. At baseline and at 3 months, patients were evaluated for exercise capacity, lung function, inspiratory muscle strength (PImax ) and work capacity (SPImax ), quality of life (QoL), LVEF and LV diameter, dyspnoea, C-reactive protein (CRP), and NT-proBNP. IMT resulted in a significantly higher benefit in SPImax (P = 0.02), QoL (P = 0.002), dyspnoea (P = 0.004), CRP (P = 0.03), and NT-proBNP (P = 0.004). In both AT/IMT and AT/SHAM groups PImax (P < 0.001, P = 0.02), peak VO2 (P = 0.008, P = 0.04), and LVEF (P = 0.005, P = 0.002) improved significantly; however, without an additional benefit for either of the groups. CONCLUSION: This randomized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF. These findings advocate for application of IMT in cardiac rehabilitation programmes.

Thyroid hormone signalling is altered in response to physical training in patients with end-stage heart failure and mechanical assist devices: potential physiological consequences?

OBJECTIVES: The present study investigated the potential of the failing myocardium of patients with ventricular assist devices (VAD) to respond to physiological growth stimuli, such as exercise, by activating growth signalling pathways. This may be of therapeutic relevance in identifying novel pharmacological targets for therapies that could facilitate recovery after VAD implantation. METHODS: Twenty-two patients bridged to heart transplantation (HTx) with VAD were included in the study. A group of patients underwent moderate intensity aerobic exercise (GT), while another group of patients did not receive exercise training (CG). Thyroid hormone receptor alpha1 (TRα1) protein and total (t) and phosphorylated (p) protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) kinase signalling were measured in myocardial tissue by western blotting at pre-VAD and pre-HTx period. In addition, Thyroid hormone (TH) levels were measured in plasma. RESULTS: Peak oxygen consumption (VO2) at pre-HTx period was higher in patients subjected to training protocol [18.0 (0.8) for GT when compared with 13.7 (0.7) for CG group, P = 0.002]. N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) levels were 1068 (148) for CG vs 626 (115) for GT group, P = 0.035. A switch towards up-regulation of physiological growth signalling was observed: the ratio of p-Akt/t-Akt was 2-fold higher in GT vs CG, P < 0.05 while p-JNK/t-JNK was 2.5-fold lower (P < 0.05) in GT vs CG, in pre-HTx samples. This response was accompanied by a 2.0-fold increase in TRα1 expression in pre-HTx samples with concomitant increase in circulating T3 in GT vs CG, P < 0.05. No differences in peak VO2, NT-proBNP, T3, TRα1, p/t-AKT and p/t-JNK were found between groups in the pre-VAD period. CONCLUSIONS: The unloaded failing myocardium responded to physical training by enhancing thyroid hormone signalling. This response was associated with an up-regulation of Akt and suppression of JNK activation.

Benefits of combined aerobic/resistance/inspiratory training in patients with chronic heart failure. A complete exercise model? A prospective randomised study.

BACKGROUND: We hypothesised that combined aerobic training (AT) with resistance training (RT) and inspiratory muscle training (IMT) could result in additional benefits over AT alone in patients with chronic heart failure (CHF). METHODS: Twenty-seven patients, age 58 ± 9 years, NYHA II/III and LVEF 29 ± 7% were randomly assigned to a 12-week AT (n=14) or a combined AT/RT/IMT (ARIS) (n=13) exercise program. AT consisted of bike exercise at 70-80% of max heart rate. ARIS training consisted of AT with RT of the quadriceps at 50% of 1 repetition maximum (1RM) and upper limb exercises using dumbbells of 1-2 kg as well as IMT at 60% of sustained maximal inspiratory pressure (SPI(max)). At baseline and after intervention patients underwent cardiopulmonary exercise testing, echocardiography, evaluation of dyspnea, muscle function and quality of life (QoL) scores. RESULTS: The ARIS program as compared to AT alone, resulted in additional improvement in quadriceps muscle strength (1RM, p=0.005) and endurance (50%1 RM × number of max repetitions, p=0.01), SPI(max) (p<0.001), exercise time (p=0.01), circulatory power (peak oxygen consumption × peak systolic blood pressure, p=0.05), dyspnea (p=0.03) and QoL (p=0.03). CONCLUSIONS: ARIS training was safe and resulted in incremental benefits in both peripheral and respiratory muscle weakness, cardiopulmonary function and QoL compared to that of AT. The present findings may add a new prospective to cardiac rehabilitation programs of heart failure patients whilst the clinical significance of these outcomes need to be addressed in larger randomised studies.

Prognostic significance of blood pressure response to exercise in patients with systolic heart failure.

High systolic blood pressure (SBP) has been linked to worse cardiovascular outcomes. However, emerging data suggest that in patients with heart failure (HF), low SBP correlates with increased mortality. The purpose was to examine the impact of baseline and post-exercise systolic and diastolic blood pressure (DBP), as well as pulse pressure (PP), on cardiac mortality in patients with systolic HF. One hundred sixty patients with systolic HF (left ventricular ejection fraction 33 ± 8) were studied. Blood pressure (BP) levels were determined at rest and at peak exercise during a cardiopulmonary exercise test. Patients were followed up for a period of 2.5 ± 0.8 years. During this period 22 patients died and 5 subjects underwent heart transplantation. Patients with higher SBP and DBP at rest, and patients with SBP ≥160 mmHg and PP ≥75 mmHg at peak exercise had the most favorable prognosis. There was a fourfold increase in cardiac mortality risk for patients with SBP <160 mmHg at peak exercise (hazard ratio: 3.97, 95% confidence interval: 1.60-9.84) and a threefold increase for patients with PP <75 mmHg at peak exercise (hazard ratio: 2.96, 95% confidence interval: 1.29-6.82). There is an inverse relationship between SBP and cardiac mortality in patients with systolic HF. BP response to exercise could serve as a simple risk stratification model in HF patients.

Prognostic value of NT-proBNP at rest and peak exercise in patients with impaired left ventricular function.

We aimed to identify whether N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) at peak exercise can provide incremental clinical information over resting levels. A total of 90 patients with systolic heart failure were prospectively studied. Levels of plasma NT-proBNP were assessed at rest and at peak exercise during a cardiopulmonary exercise test. Patients were followed-up for 30 ± 10 months. Levels of NT-proBNP at baseline and peak exercise were significantly correlated with left ventricular ejection fraction ([LVEF] r = -.629, P < .001 and r = -.630, P < .001, respectively) and peak oxygen uptake ([Vo (2)] r = -.752, P < .001 and r = -.740, P < .001, respectively). Levels of plasma NT-proBNP at peak exercise demonstrated similar predictive ability for the detection of patients with low peak Vo (2) and LVEF <28%. Levels of plasma NT-proBNP can detect low-functional class patients and patients who may be the candidates for heart transplantation with high sensitivity and specificity. At baseline and peak exercise, NT-proBNP demonstrates similar prognostic and predictive ability.

The role of NT-proBNP in explaining the variance in anaerobic threshold and VE/VCO(2) slope.

PURPOSE: We investigated whether anaerobic threshold (AT) and ventilatory efficiency (minute ventilation/carbon dioxide production slope, VE/VCO2 slope), both significantly associated with mortality, can be predicted by questionnaire scores and/or other laboratory measurements. METHODS: Anaerobic threshold and VE/VCO(2) slope, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), and the echocardiographic markers left ventricular ejection fraction (LVEF) and left atrial (LA) diameter were measured in 62 patients with heart failure (HF), who also completed the Minnesota Living with Heart Failure Questionnaire (MLHF), and the Specific Activity Questionnaire (SAQ). Linear regression models, adjusting for age and gender, were fitted. RESULTS: While the etiology of HF, SAQ score, MLHF score, LVEF, LA diameter, and logNT-proBNP were each significantly predictive of both AT and VE/VCO2 slope on stepwise multiple linear regression, only SAQ score (P < .001) and logNT-proBNP (P = .001) were significantly predictive of AT, explaining 56% of the variability (adjusted R(2) = 0.525), while logNT-proBNP (P < .001) and etiology of HF (P = .003) were significantly predictive of VE/VCO(2) slope, explaining 49% of the variability (adjusted R(2) = 0.45). The area under the ROC curve for NT-proBNP to identify patients with a VE/VCO(2) slope greater than 34 and AT less than 11 mL · kg(-1) · min(-1) was 0.797; P < .001 and 0.712; P = .044, respectively. A plasma concentration greater than 429.5 pg/mL (sensitivity: 78%; specificity: 70%) and greater than 674.5 pg/mL (sensitivity: 77.8%; specificity: 65%) identified a VE/VCO(2) slope greater than 34 and AT lower than 11 mL · kg(-1) · min(-1), respectively. CONCLUSIONS: NT-proBNP is independently related to both AT and VE/VCO(2) slope. Specific Activity Questionnaire score is independently related only to AT and the etiology of HF only to VE/VCO(2) slope.

Benefits of physical training on exercise capacity, inspiratory muscle function, and quality of life in patients with ventricular assist devices long-term postimplantation.

BACKGROUND: Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device (VAD) implantation. The benefits of exercise training in patients with VAD are unknown. DESIGN AND METHODS: Fifteen patients, aged 38.3 ± 15.9 years, bridged to heart transplantation with left ventricular assist device or biventricular assist device were randomized at a ratio of 2 : 1 to a training group (TG, n = 10) or a control group (n = 5), 6.3 ± 4 months after implantation. Both the groups were advised to walk 30­45 min/day. TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min, three to five times a week, combined with high-intensity inspiratory muscle training using a computer-designed software to respiratory exhaustion, two to three times a week for 10 weeks. The patients were tested using cardiopulmonary exercise testing, 6-min walk test, spirometry and electronic pressure manometer for inspiratory muscle strength (Pimax) and endurance (sustained Pimax) measurement. Quality of life was assessed with the Minnesota Living with Heart Failure questionnaire. RESULTS: TG improved peak oxygen consumption (19.3 ± 4.5 vs. 16.8 ± 3.7 ml/kg per min, P = 0.008) and VO2 at ventilatory threshold (15.1 ± 4.2 vs. 12 ± 5.6 ml/kg per min, P = 0.01), whereas the ventilation/carbon dioxide slope decreased (35.9 ± 5.6 vs. 40 ± 6.5, P = 0.009). The 6-min walk test distance increased (527 ± 76 vs. 462 ± 88 m, P = 0.005) and quality of life was improved (38.2 ± 11.6 vs. 48.9 ± 12.8, P = 0.005), as well as Pimax (131.8 ± 33 vs. 95.5 ± 28cmH2O, P = 0.005), sustained Pimax (484 ± 195 vs. 340 ± 193cmH2O/s/103, P = 0.005), and inspiratory lung capacity (2.4 ± 0.9 vs. 1.7 ± 0.7 L, P = 0.008) were improved. No significant changes were noted in the control group. CONCLUSION: Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus, may have additional importance in cases of destination therapy.

Stress test with dual isotope studies for the documentation of classical ischemic preconditioning.

OBJECTIVES: We investigated whether myocardial perfusion imaging (MPI) can demonstrate the effect of classical preconditioning. METHODS: 21 patients with documented coronary artery disease (stenosis>or=70%) underwent two exercise stress tests (EST) with concomitant MPI, using TL-201 for the first and tetrofosmin-Tc-99m for the second. A third MPI was performed at rest, using Tc-99m. Total defect score was derived by summing tracer uptake in a 17 segments left ventricle model, graded on a 5-point scale. Tomographic images were also analyzed quantitatively, to derive the total defect size. RESULTS: Maximum ST depression did not differ significantly between the two EST (2.2+/-1 vs 2.2+/-1 mm, p=NS), however in the second EST longer times for onset of ischemic changes (228+/-94 vs 265+/-103 s, p=0.01) and appearance of angina (282+/-153 vs 328+/-177 s, p=0.04) were observed. Exercise perfusion abnormalities were significantly lower in the second MPI, in terms of both total defect score (19.2+/-11.5 vs 10+/-10.4, p<0.0001) and total defect size (28.3+/-16.9 vs 13.8+/-15.8, p<0.0001). CONCLUSION: Significant improvement in perfusion pattern was demonstrated in the second MPI, accompanied by delayed appearance of ischemic manifestations. The improvement in myocardial perfusion extends far beyond the changes that can be attributed to differences in myocardial uptake between tracers, reflecting the effect of classical preconditioning.

Comparative value of NYHA functional class and quality-of-life questionnaire scores in assessing heart failure.

PURPOSE: To assess the relationships between New York Heart Association (NYHA) functional class, quality of life, aerobic capacity (peak oxygen uptake, (.)VO2), ventilatory efficiency (minute ventilation/carbon dioxide production slope, VE/(.)VCO2 slope), and brain natriuretic peptide (BNP) in creating a model for predicting peak (.)VO2). METHODS: Cardiopulmonary exercise testing was performed in 62 patients. A baseline blood sample was taken to measure the N-terminal prohormone BNP (NT-proBNP). Patients also completed the Minnesota Living with Heart Failure Questionnaire (MLHF) and the Specific Activity Questionnaire (SAQ), and NYHA functional class was determined. RESULTS: NYHA functional class correlated more strongly with SAQ score than with MLHF score. Peak (.)VO2 and VE/(.)VCO2 slope had stronger associations with NYHA functional class and SAQ score than with MLHF score. NT-proBNP plasma levels correlated more significantly with NYHA functional class and SAQ score (both P < .001) than with MLHF score. Using multiple linear regression analysis adjusted for age and sex, SAQ score, NT-proBNP, and etiology of heart failure had significant independent relationships with peak (.)VO2, explaining 63% of its variability (adjusted R(2) = 0.596). CONCLUSIONS: Cardiopulmonary exercise variables and plasma NT-proBNP are associated more with NYHA functional class and SAQ score than with MLHF score. When combined, SAQ score, NT-proBNP, and etiology of heart failure can satisfactorily predict peak oxygen uptake.

Explanation of the variance in quality of life and activity capacity of patients with heart failure by laboratory data.

BACKGROUND: This study was conducted to explain the variance in quality of life (QoL) and activity capacity of patients with congestive heart failure from pathophysiological changes as estimated by laboratory data. METHODS: Peak oxygen consumption (peak VO2) and ventilation (VE)/carbon dioxide output (VCO2) slope derived from cardiopulmonary exercise testing, plasma N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and echocardiographic markers [left atrium (LA), left ventricular ejection fraction (LVEF)] were measured in 62 patients with congestive heart failure, who also completed the Minnesota Living with Heart Failure Questionnaire and the Specific Activity Questionnaire. All regression models were adjusted for age and sex. RESULTS: On linear regression analysis, peak VO2 with P value less than 0.001, VE/VCO2 slope with P value less than 0.01, LVEF with P value less than 0.001, LA with P=0.001, and logNT-proBNP with P value less than 0.01 were found to be associated with QoL. On stepwise multiple linear regression, peak VO2 and LVEF continued to be predictive, accounting for 40% of the variability in Minnesota Living with Heart Failure Questionnaire score. On linear regression analysis, peak VO2 with P value less than 0.001, VE/VCO2 slope with P value less than 0.001, LVEF with P value less than 0.05, LA with P value less than 0.001, and logNT-proBNP with P value less than 0.001 were found to be associated with activity capacity. On stepwise multiple linear regression, peak VO2 and LA continued to be predictive, accounting for 53% of the variability in Specific Activity Questionnaire score. CONCLUSION: Peak VO2 is independently associated both with QoL and activity capacity. In addition to peak VO2, LVEF is independently associated with QoL, and LA with activity capacity.

High plasma adiponectin is related to low functional capacity in patients with chronic heart failure.

We evaluated the association between plasma adiponectin and functional capacity in patients with chronic heart failure (CHF). Similarly to NT-proBNP, plasma adiponectin was elevated in CHF compared to healthy controls. Adiponectin correlated inversely with peak oxygen consumption and 6-minute walking distance and was able to identify CHF patients with impaired exercise capacity. Our findings support a role of adiponectin as an index of heart failure severity.

Effect of iron overload on exercise capacity in thalassemic patients with heart failure.

In b-thalassemia, myocardial iron overload contributes to heart failure, despite chelation treatment. We hypothesized that myocardial T2*, an index of iron overload, influences patients' physical activity. We assessed a thalassemic population by both cardiovascular magnetic resonance imaging (CMR) and ergospirometry test. Sixty-six thalassemic patients aged 27 (19-40) years, 30 without (NHF) and 36 with heart failure (HF), were studied. Cardiac T2* and left ventricular ejection fraction (LVEF) were evaluated using a 1.5 T system. VO(2max), AT, Mets and duration of exercise by ergospirometry were also assessed. Myocardial T2* was lower in HF compared to NHF patients (14.7 +/- 6.6 vs. 39 +/- 2 ms, P < 0.001). LVEDV and LVESV were higher in HF group compared to NHF patients (139.9 +/- 16.3 vs. 124.6 +/- 20.86 ml, P < 0.01 and 94.9 +/- 24 vs. 38.3 +/- 10.1 ml, P < 0.001, respectively). Additionally, LVEF in HF was lower compared to NHF patients (21.3 +/- 6.1% vs. 69.6 +/- 3.7, P < 0.001, respectively). All exercise parameters were lower in HF compared to NHF patients (P < 0.001). Patients within the HF group were additionally analyzed according to T2* values (<10 ms). HF patients with T2* < 10 ms (n = 13) were considered as high iron overloaded (HF-H) and the rest of them (n = 23) as (HF-L). Although LVEDV, LVESV, LVEF were similar in the two subgroups, the exercise parameters were significantly lower in the HF-H group (P < 0.001). Heart T2* correlated with all exercise parameters (P < 0.001). HF thalassemic patients have reduced exercise indexes compared to non HF. Myocardial iron overload, expressed as T2*, has a direct influence on exercise capacity, independent of LV ejection fraction and functional class.

Assessment of quality of life using three activity questionnaires in heart failure patients after monthly, intermittent administration of levosimendan during a six-month period.

INTRODUCTION: Quality of life (QOL) in heart failure patients is severely compromised by the symptoms of the disease. Acute administration of levosimendan improves patients' symptoms for intervals of 7-10 days. The aim of this study was to assess the QOL in heart failure patients, after monthly, intermittent administration of levosimendan for a 6-month period, using 3 activity questionnaires: Specific Activity Questionnaire (SAQ), Left Ventricular Dysfunction 36 (LVD 36), and Minnesota Living with Heart Failure Questionnaire (LIhFE). METHODS: We prospectively studied 20 patients, age 61.0 +/- 15.7 years (mean +/- SD) with heart failure (NYHA III and IV). Levosimendan was administered intravenously for 24 hours (dose 0.1 mg/kg/min), 1 day every month for a 6-month period. Patients were asked to answer the questions of the 3 activity questionnaires SAQ, LVD36 and LIhFE before and after the end of the 6-month period. RESULTS: For the LIhFE (the best score is 0 and the worst 105) before levosimendan the score was 35.4 +/- 18.6 and after 6 months 22.2 +/- 13.0 (p<0.0001). SAQ (worst score is 0 and the best is 9) before levosimendan was 4.2 +/- 1.6 and after 6 months 4.7 +/- 1.3 (p<0.05). For the LVD36 (more ;right' answers, more severe condition) before levosimendan values were 52.6 +/- 26.2 and after 6 months 27.4 +/- 17.3 (p<0.0001). Before levosimendan patients had a mean left ventricular ejection fraction (LVEF) 30.3 +/- 6.9, while after 6 months the LVEF was 32.1 +/- 7.4 (p=0.01). CONCLUSIONS: Levosimendan treatment improved both objective echocardiographic measurements and the subjective QOL questionnaires. LIhFE and LVD36 show a significant improvement in QOL in heart failure patients after a 6-month period of monthly intermittent administration of levosimendan. The SAQ showed a very small improvement, because it describes more strenuous activity, a situation unusual for these patients, who are severely symptom limited.

Incremental value of N-terminal pro-brain natriuretic peptide over left ventricle ejection fraction and aerobic capacity for estimating prognosis in heart failure patients.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels have been associated with indices of left ventricular (LV) function and aerobic capacity in heart failure. METHODS: We prospectively followed-up 149 patients with impaired left ventricular function for 30 +/- 10 months. During this period, 22 patients died and 5 underwent heart transplantation. Blood samples for NT-proBNP assessment were taken at baseline and before cardiopulmonary exercise to estimate peak oxygen consumption (Vo(2)). LV cavity diameter, left atrial size and LV ejection fraction (LVEF) were measured by echocardiography. RESULTS: NT-proBNP plasma levels >1,164 pg/ml showed 85% sensitivity and 82% specificity for detecting Vo(2)<14 ml/kg/min (area under the curve [AUC] = 90%, p < 0.001). Patients above this cutoff showed a 13.6-fold greater hazard ratio compared with those with values below this cutoff (p < 0.001). NT-proBNP plasma levels of >760 pg/ml showed 77% sensitivity and 69% specificity for detecting LVEF <28% (AUC = 77%, p < 0.001). Patients with values above this cutoff showed a 15.85-fold greater hazard ratio compared to those with values below this cutoff (p < 0.001). The addition of NT-proBNP to an assessment model that includes peak Vo(2), LVEF and New York Heart Association (NYHA) classification can significantly improve predictive ability. CONCLUSIONS: Assessment of NT-proBNP should be performed to detect candidates for heart transplantation because of the useful prognostic information that it can provide.