Exercise-induced biphasic increase in circulating NT-proBNP levels in patients with chronic heart failure.

BACKGROUND: Exercise increases natriuretic peptide levels in chronic heart failure (CHF) patients, but the effect is considered minor. We assessed acute and short-term release (<24 h) of NT-proBNP in CHF patients after a maximal cardiopulmonary exercise test (CPET) and 2 different submaximal training sessions. METHODS AND RESULTS: 102 CHF patients either performed CPET (Group 1), a 1 h endurance (Group 2) or a combined endurance-resistance training session (Group 3). NT-proBNP concentration was determined before, at exercise cessation and after 18-22 h (Protocol A). In 20 patients, samples were obtained before, at exercise cessation, after 15, 30, 45, 60, 90 min, 2, 3, 4, 5, 6, 12, 22 h (Protocol B). Protocol A: At peak exercise, a 15%, 11% and 17% relative increase (p<0.001 vs baseline, all 3 groups) was seen, with a return to baseline after 18-22 h. The increase correlated with indicators of more advanced heart failure. Protocol B: A biphasic pattern was derived with a first peak within 1 h of exercise termination and a second peak (39%, 31% and 33% higher than baseline; p<0.05, all 3 groups) after 4-12 h. CONCLUSIONS: The observed biphasic release of B-type natriuretic peptides supports standardization of sampling, taking recent exercise into account.

Rate response and cardiac resynchronisation therapy in chronic heart failure: higher cardiac output does not acutely improve exercise performance: a pilot trial.

BACKGROUND: Rate adaptive pacing (RAP) during cardiac resynchronisation therapy (CRT) in patients with chronic heart failure (CHF) might improve exercise capacity through enhanced cardiac output (CO). Conversely, higher heart rates (HR) might set off a blunted force-frequency response (FFR). METHODS: Fourteen CRT-treated patients (62+/-3 years, left ventricular ejection fraction 30.8+/-2.7%) underwent two cardiopulmonary exercise tests (CPET). CPET1: rate response off; CPET2: rate response on. Conventional and tissue doppler echocardiography were obtained at rest and at peak exercise. RESULTS: Peak values for HR (106+/-5 vs. 127+/-3 bpm; P=0.001) and CO (6.4+/-0.4 vs. 7.4+/-0.4 l/min/m; P=0.001) increased significantly comparing CPET1 and CPET2. Stroke volume index (28.8+/-1.4 vs. 27.9+/-1.2 ml/m, P=0.2) and peak oxygen consumption (17.8+/-0.9 vs. 17.4+/-0.7 ml/kg/min, P=0.6), however, did not differ. Longitudinal systolic velocities of the basal septum (SSm: 6.9+/-0.9 vs. 6.1+/-0.8 cm/s, P=0.07), basal left lateral (LSm: 6.1+/-1.3 vs. 5.9+/-0.8 cm/s, P=0.3) and basal right ventricular free wall (RVSm: 11.7+/-0.9 vs. 10.1+/-0.7 cm/s, P<0.01) remained unchanged or decreased. Inter-ventricular (Deltat LSm-RVSm) (10+/-18 vs. 15+/-9 ms) and intra-ventricular mechanical delay (Deltat SSm-LSm) (10+/-15 vs. 9+/-6 ms) did not change. CONCLUSION: RAP resulted in a net increase in CO, without an acute favourable effect on exercise capacity. This finding underscores the importance of peripheral factors (endothelial and skeletal muscle dysfunction) as determinants of exercise capacity in CHF. The fact that longitudinal systolic myocardial velocities at higher HR did not change or even decreased suggests that a blunted FFR still occurs, despite CRT. RAP had no effect on mechanical synchrony.

Quantification of circulating endothelial progenitor cells: a methodological comparison of six flow cytometric approaches.

OBJECTIVES: The validity of endothelial progenitor cells as biomarkers and their therapeutic potential depend on the accuracy of techniques used for enumeration. This study assessed the agreement between 6 flow cytometric methods and a CFU assay used for EPC quantification. METHODS: Two blood samples were obtained from 30 healthy volunteers (60 samples). CD34+/VEGFR2+ cells were analyzed with flow cytometry, starting from whole blood (A-C) or PBMC (D-F), using different gating strategies: A: lymphocyte gating; B and D: exclusion of autofluorescent cells (CD3 negative selection); C and E: exclusion of autofluorescence and cell aggregates (pulse shape analysis by FSCarea/FSCpeak); F: exclusion of autofluorescence, cell aggregates and non-nucleated cells (Draq 5). PBMC were cultured under endothelial cell conditions to assess CFU numbers. RESULTS: Moderate agreement was found between methods B-C and D-E (ICC 0.647 and 0.530). Comparison of methods B-D and C-E showed poor agreement (ICC 0.178 and 0.249). This was also the case for techniques that considerably differed with regard to gating strategies (A-B, A-F, B-F). CFU numbers did not correlate with flow cytometric quantification (all p>0.05). CONCLUSIONS: Agreement between methods for EPC quantification is moderate to poor, which may explain apparent controversies in literature. Although each protocol is highly reproducible, this study cautions against comparing study results gathered with different enumeration techniques.

A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects. Relation with lipid profile.

Mobilization of bone marrow-derived endothelial progenitor cells (EPC) might explain exercise-induced improvement of endothelial function. We assessed whether a maximal exercise bout could alter the number of circulating EPC in healthy subjects and whether this effect is related to their cardiovascular risk profile. Additionally, we investigated possible mediators of this effect, namely nitric oxide (NO) bioavailability and vascular endothelial growth factor (VEGF) release. Healthy subjects (group 1, n = 11; group 2, n = 14) performed a symptom-limited cardiopulmonary exercise test on a bicycle ergometer. Numbers of CD34+/kinase insert domain receptor (KDR)+ cells were determined by flow-cytometric analysis, either after magnetic separation of CD34+ cells (group 1) or starting from whole blood (group 2). Serum concentrations of VEGF and NO metabolites were measured by using ELISA. Following exercise, EPC increased by 76% (15.4 +/- 10.7 cells/ml vs. 27.2 +/- 13.7 cells/ml; P = 0.01) in group 1 and by 69% in group 2 (30.9 +/- 14.6 cells/ml vs. 52.5 +/- 42.6 cells/ml; P = 0.03). The increase in EPC correlated positively with LDL and total cholesterol/HDL ratio and negatively with peak oxygen consumption and oxygen consumption at anaerobic threshold. VEGF levels increased with exercise, with a strong trend toward significance (P = 0.055). NO levels remained unchanged. The present study demonstrates that a maximal bout of exercise induces a significant shift in CD34+ cells toward CD34+/KDR+ cells. This response was larger in subjects with a less favorable lipid profile.

Heart failure and cachexia: insights offered from molecular biology.

Chronic heart failure (CHF) is an enormous medical and communal burden. The syndrome is common, carries a grim prognosis and severely impacts quality of life. Those patients who develop cardiac cachexia combat both important disability and a poor outlook. Muscle wasting is a critical component of cachexia. The pathophysiological determinants are numerous and some of them are common to other chronic severe illnesses. There is increasing awareness, however, that heart failure related myopathy is a distinct entity, characterized by specific functional, structural and morphologic changes and the involvement of several neurohormonal pathways, catabolic processes, a pro-inflammatory environment and increased oxidative stress. Although clear-cut evidence based solutions for the problem are not readily available, the modulating effects of regular exercise in CHF patients suggest that physical training should at least be incorporated in the essentially multi-disciplinary approach.

The effect of endurance training on exercise capacity following cardiac resynchronization therapy in chronic heart failure patients: a pilot trial.

BACKGROUND: Both endurance training (ET) and cardiac resynchronization therapy (CRT) improve quality of life (QOL) and exercise tolerance in patients with advanced chronic heart failure (CHF). DESIGN: A randomized intervention trial to study the effect on exercise capacity of ET in addition to CRT in patients with CHF and dyssynchrony. METHODS: Seventeen patients (eight men, aged 59+/-9 years) with CHF and dyssynchrony were randomized to CRT with (n=8) or without (n=9) ET and compared with two matched control CHF groups (standard care with ET: n=9, standard care only: n=10). At baseline and after 5 months, exercise tolerance, left ventricular (LV) remodelling, QOL and NT-pro brain natriuretic peptide (NT-proBNP) levels were assessed. RESULTS: Peak oxygen consumption (VO2peak), maximal workload (Wattmax), circulatory power, LV ejection fraction, dyssynchrony and QOL improved in both CRT groups. However, the increase in VO2peak (+40% versus +16%, P=0.005), Wattmax (+43% versus +13%, P=0.0005), and circulatory power (+74% versus +32%, P=0.01), was significantly greater in the trained versus the untrained CRT patients. Comparison of the four patient groups confirmed the cumulative effects of CRT plus ET. CONCLUSIONS: ET in resynchronized CHF patients is feasible and further enhances exercise tolerance. Patients with severe CHF should be prescribed an exercise training programme after implantation in order to maximize the expected benefit.