Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

AIMS Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure. METHODS AND RESULTS We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Muscle wasting was identified using dual-energy X-ray absorptiometry (DEXA) in 38 patients (19.4%). Patients with muscle wasting demonstrated higher CAF values than those without (125.1 ± 59.5 pmol/L vs. 103.8 ± 42.9 pmol/L, P = 0.01). Using receiver operating characteristics (ROC), we calculated the optimal CAF value to identify patients with muscle wasting as >87.5 pmol/L, which had a sensitivity of 78.9% and a specificity of 43.7%. The area under the ROC curve was 0.63 (95% confidence interval 0.56-0.70). Using simple regression, we found that serum CAF was associated with handgrip (R = - 0.17, P = 0.03) and quadriceps strength (R = - 0.31, P < 0.0001), peak oxygen consumption (R = - 0.5, P < 0.0001), 6-min walk distance (R = - 0.32, P < 0.0001), and gait speed (R = - 0.2, P = 0.001), as well as with parameters of kidney and liver function, iron metabolism and storage. CONCLUSION CAF shows good sensitivity for the detection of skeletal muscle wasting in patients with heart failure. Its assessment may be useful to identify patients who should undergo additional testing, such as detailed body composition analysis. As no other biomarker is currently available, further investigation is warranted.

Good reproducibility of heart rate variability after orthostatic challenge in patients with a history of acute coronary syndrome

BACKGROUND: Several parameters of heart rate variability (HRV) have been shown to predict the risk of sudden cardiac death (SCD) in cardiac patients. There is consensus that risk prediction is increased when measuring HRV during specific provocations such as orthostatic challenge. For the first time, we provide data on reproducibility of such a test in patients with a history of acute coronary syndrome. METHODS: Sixty male patients (65+/-8years) with a history of acute coronary syndrome on stable medication were included. HRV was measured in supine (5min) and standing (5min) position on 2 occasions separated by two weeks. For risk assessment relevant time-domain [standard deviation of all R-R intervals (SDNN) and root mean squared standard differences between adjacent R-R intervals (RMSSD)], frequency domain [low-frequency power (LF), high-frequency power (HF) and LF/HF power ratio] and short-term fractal scaling component (DF1) were computed. Absolute reproducibility was assessed with the standard errors of the mean (SEM) and 95% limits of random variation, and relative reproducibility by the intraclass correlation coefficient (ICC). RESULTS: We found comparable SEMs and ICCs in supine position and after an orthostatic challenge test. All ICCs were good to excellent (ICCs between 0.636 and 0.869). CONCLUSIONS: Reproducibility of HRV parameters during orthostatic challenge is good and comparable with supine position.

Sex differences in heart rate variability: a longitudinal study in international elite cross-country skiers

PURPOSE: Exercise-related sudden cardiac deaths (SCD) occur with a striking male predominance. A higher sympathetic tone in men has been suggested as risk factor for SCD. Elite athletes have the highest risk for exercise-related SCD. We aimed to analyze the autonomic nervous system of elite cross-country skiers from Norway, Russia and Switzerland in supine position and after orthostatic challenge in various training periods (TP). METHOD: Measurements of heart rate variability (HRV) were performed on a weekly basis over 1 year using an orthostatic challenge test with controlled breathing. Main outcome parameters were the high-frequency power in supine position (HFsupine) as marker of cardiac parasympathetic activity and the low-frequency/high-frequency power ratio after orthostatic challenge (LF/HFstand) as marker of cardiac sympathetic activation. Training intensity and duration were recorded daily and expressed as training strain. The training year was divided into three TPs. An average of weekly HRV measurements was calculated for each TP. RESULT: Female (n = 19, VO2max 62.0 +/- 4.6 ml kg(-1) min(-1), age 25.8 +/- 4.3 years) and male (n = 16, VO2max 74.3 +/- 6.3 ml kg(-1) min(-1), age 24.4 +/- 4.2 years) athletes were included. Training strain was comparable between sexes (all p > 0.05) and changed between TPs (all p < 0.05) while no HRV parameters changed over time. There were no sex differences in HFsupine while the LF/HFstand was significantly higher in male athletes in all TPs. CONCLUSION: For a comparable amount of training, male athletes showed constantly higher markers of sympathetic activity after a provocation maneuver. This may explain part of the male predominance in sports-related SCD.

Efficacy of mechanical postconditioning following warm, global ischaemia depends on circulating fatty acid levels in an isolated, working rat heart model

Gebiet: Chirurgie Abstract: OBJECTIVES: – The number of heart transplantations is limited by donor organ availability. Donation after circulatory determination of death (DCDD) could significantly improve graft availability, however, organs undergo warm ischaemia followed by reperfusion, leading to tissue damage. Laboratory studies suggest that mechanical postconditioning [(MPC), brief, intermittent periods of ischaemia at the onset of reperfusion] can limit reperfusion injury, however, clinical translation has been disappointing. We hypothesized that MPC-induced cardioprotection depends on fatty acid levels at reperfusion. – – METHODS: – Experiments were performed with an isolated rat heart model of DCDD. Hearts of male Wistar rats (n = 42) underwent working-mode perfusion for 20 min (baseline), 27 min of global ischaemia and 60 min reperfusion with or without MPC (two cycles of 30 s reperfusion/30 s ischaemia) in the presence or absence of high fat [(HF), 1.2 mM palmitate]. Haemodynamic parameters, necrosis factors and oxygen consumption (O2C) were assessed. Recovery rate was calculated as the value at 60 min reperfusion expressed as a percentage of the mean baseline value. The Kruskal-Wallis test was used to provide an overview of differences between experimental groups, and pairwise comparisons were performed to compare specific time points of interest for parameters with significant overall results. – – RESULTS: – Percent recovery of left ventricular (LV) work [developed pressure (DP)-heart rate product] at 60 min reperfusion was higher in hearts reperfused without fat versus with fat (58 ± 8 vs 23 ± 26%, P < 0.01) in the absence of MPC. In the absence of fat, MPC did not affect post-ischaemic haemodynamic recovery. Among the hearts reperfused with HF, two significantly different subgroups emerged according to recovery of LV work: low recovery (LoR) and high recovery (HiR) subgroups. At 60 min reperfusion, recovery was increased with MPC versus no MPC for LV work (79 ± 6 vs 55 ± 7, respectively, P < 0.05) in HiR subgroups and for DP (40 ± 27 vs 4 ± 2%), dP/dtmax (37 ± 24 vs 5 ± 3%) and dP/dtmin (33 ± 21 vs 5 ± 4%, P < 0.01 for all) in LoR subgroups. – – CONCLUSIONS: – Effects of MPC depend on energy substrate availability, MPC increased recovery of LV work in the presence, but not in the absence, of HF. Controlled reperfusion may be useful for therapeutic strategies aimed at improving post-ischaemic recovery of cardiac DCDD grafts, and ultimately in increasing donor heart availability.

Postmortem magnetic resonance imaging: Reproducing typical autopsy heart measurements

PURPOSE The aim of this study was to evaluate the utility of cardiac postmortem magnetic resonance (PMMR) to perform routine measurements of the ventricular wall thicknesses and the heart valves and to assess if imaging measurements are consistent with traditional autopsy measurements. METHODS In this retrospective study, 25 cases with cardiac PMMR and subsequent autopsy were included. The thicknesses of the myocardial walls as well as the circumferences of all heart valves were measured on cardiac PMMR and compared to autopsy measurements. Paired samples T-test and the Wilcoxon-Signed rank test, were used to compare autopsy and cardiac PMMR measurements. For exploring correlations, the Pearson's Correlation coefficient and the Spearman's Rho test were used. RESULTS Cardiac PMMR measurements of the aortic and pulmonary valve circumferences showed no significant differences from autopsy measurements. The mitral and tricuspid valves circumferences differed significantly from autopsy measurements. Left myocardial and right myocardial wall thickness also differed significantly from autopsy measurements. Left and right myocardial wall thickness, and tricuspid valve circumference measurements on cardiac PMMR and autopsy, correlated strongly and significantly. CONCLUSION Several PMMR measurements of cardiac parameters differ significantly from corresponding autopsy measurements. However, there is a strong correlation between cardiac PMMR measurements and autopsy measurements in the majority of these parameters. It is important to note that myocardial walls are thicker when measured in situ on cardiac PMMR than when measured at autopsy. Investigators using post-mortem MR should be aware of these differences in order to avoid false diagnoses of cardiac pathology based on cardiac PMMR.

Long Term Outcomes Following Catheter Ablation of Ventricular Tachycardia in Patients with and without Structural Heart Disease.

BACKGROUND Long-term outcomes following ventricular tachycardia (VT) ablation are sparsely described. OBJECTIVES To describe long term prognosis following VT ablation in patients with no structural heart disease (no SHD), ischemic (ICM) and non-ischemic cardiomyopathy (NICM). METHODS Consecutive patients (n=695; no SHD 98, ICM 358, NICM 239 patients) ablated for sustained VT were followed for a median of 6 years. Acute procedural parameters (complete success [non-inducibility of any VT]) and outcomes after multiple procedures were reported. RESULTS Compared with patients with no SHD or NICM, ICM patients were the oldest, had more males, lowest left ventricular ejection fraction (LVEF), highest drug failures, VT storms and number of inducible VTs. Complete procedure success was highest in no SHD, compared ICM and NICM patients (79%, 56%, 60% respectively, P<0.001). At 6 years, ventricular arrhythmia (VA)-free survival was highest in no SHD (77%) than ICM (54%) and NICM (38%, P<0.001) and overall survival was lowest in ICM (48%), followed by NICM (74%) and no SHD patients (100%, P<0.001). Age, LVEF, presence of SHD, acute procedural success (non-inducibility of any VT), major complications, need for non-radiofrequency ablation modalities, and VA recurrence were independently associated with all cause mortality. CONCLUSIONS Long term follow up following VT ablation shows excellent prognosis in the absence of SHD, highest VA recurrence and transplantation in NICM and highest mortality in patients with ICM. The extremely low mortality for those without SHD suggests that VT in this population is very rarely an initial presentation of a myopathic process.