Gait analysis in chronic heart failure: The calf as a locus of impaired walking capacity

Reduced walking capacity, a hallmark of chronic heart failure (CHF), is strongly correlated with hospitalization and morbidity. The aim of this work was to perform a detailed biomechanical gait analysis to better identify mechanisms underlying reduced walking capacity in CHF. Inverse dynamic analyses were conducted in CHF patients and age- and exercise level-matched control subjects on an instrumented treadmill at self-selected treadmill walking speeds and at speeds representing +20% and -20% of the subjects' preferred speed. Surprisingly, no difference in preferred speed was observed between groups, possibly explained by an optimization of the mechanical cost of transport in both groups (the mechanical cost to travel a given distance; J/kg/m). The majority of limb kinematics and kinetics were also similar between groups, with the exception of greater ankle dorsiflexion angles during stance in CHF. Nevertheless, over two times greater ankle plantarflexion work during stance and per distance traveled is required for a given triceps surae muscle volume in CHF patients. This, together with a greater reliance on the ankle compared to the hip to power walking in CHF patients, especially at faster speeds, may contribute to the earlier onset of fatigue in CHF patients. This observation also helps explain the high correlation between triceps surae muscle volume and exercise capacity that has previously been reported in CHF. Considering the key role played by the plantarflexors in powering walking and their association with exercise capacity, our findings strongly suggest that exercise-based rehabilitation in CHF should not omit the ankle muscle group

Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model

Background Pulmonary hypertension leads to right ventricular heart failure and ultimately to cardiac cachexia. Cardiac cachexia induces skeletal muscles atrophy and contractile dysfunction. MAFbx and MuRF1 are two key proteins that have been implicated in chronic muscle atrophy of several wasting states. Methods Monocrotaline (MCT) was injected over eight weeks into mice to establish pulmonary hypertension as a murine model for cardiac cachexia. The effects on skeletal muscle atrophy, myofiber force, and selected muscle proteins were evaluated in wild-type (WT), MuRF1, and MuRF2-KO mice by determining muscle weights, in vitro muscle force and enzyme activities in soleus and tibialis anterior (TA) muscle. Results In WT, MCT treatment induced wasting of soleus and TA mass, loss of myofiber force, and depletion of citrate synthase (CS), creatine kinase (CK), and malate dehydrogenase (MDH) (all key metabolic enzymes). This suggests that the murine MCT model is useful to mimic peripheral myopathies as found in human cardiac cachexia. In MuRF1 and MuRF2-KO mice, soleus and TA muscles were protected from atrophy, contractile dysfunction, while metabolic enzymes were not lowered in MuRF1 or MuRF2-KO mice. Furthermore, MuRF2 expression was lower in MuRF1KO mice when compared to C57BL/6 mice. Conclusions In addition to MuRF1, inactivation of MuRF2 also provides a potent protection from peripheral myopathy in cardiac cachexia. The protection of metabolic enzymes in both MuRF1KO and MuRF2KO mice as well as the dependence of MuRF2 expression on MuRF1 suggests intimate relationships between MuRF1 and MuRF2 during muscle atrophy signaling

Low skeletal muscle mass is associated with low aerobic capacity and increased mortality risk in patients with coronary heart disease: A CARE CR Study

Background In patients with chronic heart failure, there is a positive linear relationship between skeletal muscle mass (SMM) and peak oxygen consumption (urn:x-wiley:14750961:media:cpf12539:cpf12539-math-0001O2peak); an independent predictor of all‐cause mortality. We investigated the association between SMM and urn:x-wiley:14750961:media:cpf12539:cpf12539-math-0002O2peak in patients with coronary heart disease (CHD) without a diagnosis of heart failure. Methods Male patients with CHD underwent maximal cardiopulmonary exercise testing and dual X‐ray absorptiometry assessment. urn:x-wiley:14750961:media:cpf12539:cpf12539-math-0003O2peak, the ventilatory anaerobic threshold and peak oxygen pulse were calculated. SMM was expressed as appendicular lean mass (lean mass in both arms and legs) and reported as skeletal muscle index (SMI; kg m−2), and as a proportion of total body mass (appendicular skeletal mass [ASM%]). Low SMM was defined as a SMI <7·26 kg m−2, or ASM% <25·72%. Five‐year all‐cause mortality risk was calculated using the Calibre 5‐year all‐cause mortality risk score. Results Sixty patients were assessed. Thirteen (21·7%) had low SMM. SMI and ASM% correlated positively with urn:x-wiley:14750961:media:cpf12539:cpf12539-math-0004O2peak (r = 0·431 and 0·473, respectively; P<0·001 for both). SMI and ASM% predicted 16·3% and 12·9% of the variance in urn:x-wiley:14750961:media:cpf12539:cpf12539-math-0005O2peak, respectively. SMI correlated most closely with peak oxygen pulse (r = 0·58; P<0·001). SMI predicted 40·3% of peak urn:x-wiley:14750961:media:cpf12539:cpf12539-math-0006O2/HR variance. ASM% was inversely associated with 5‐year all‐cause mortality risk (r = −0·365; P = 0·006). Conclusion Skeletal muscle mass was positively correlated with urn:x-wiley:14750961:media:cpf12539:cpf12539-math-0007O2peak in patients with CHD. Peak oxygen pulse had the strongest association with SMM. Low ASM% was associated with a higher risk of all‐cause mortality. The effects of exercise and nutritional strategies aimed at improving SMM and function in CHD patients should be investigated

Risk factors, co-morbidities and hemodynamic changes in patients with chronic heart failure

Einleitung: Die Herzinsuffizienz ist eine Erkrankung mit hoher Prävalenz und sehr schlechter Prognose. Daher kommt der Forschung auf diesem Gebiet immer mehr Bedeutung zu. Vor allem die Untersuchung von Begleiterkrankungen und die Reduktion von Risikofaktoren spielen dabei eine große Rolle. Ziel dieser Arbeit war es deshalb, wichtige, bisher nicht oder unzureichend erforschte Komorbiditäten wie den Muskelmasseverlust zu untersuchen, Risikofaktoren wie das Rauchverhalten anhand der Verlässlichkeit von Patientenaussagen zu evaluieren und Untersuchungsmethoden zu etablieren, die es ermöglichen, auf einfachem Weg Aussagen zu hämodynamischen Veränderungen bei Patienten mit chronischer Herzinsuffizienz zu treffen. Methoden und Ergebnisse: Verlust von Muskelmasse und -funktion (P 1) im fortgeschrittenen Alter ist ein in der Geriatrie bekanntes Phänomen, das als Sarkopenie bezeichnet wird. Die Magermasse als Maß der Muskelmasse wurde mittels Dual Energy X-Ray Absorptiometry (DEXA) bei 200 Patienten bestimmt. Weiterhin wurden Tests zur Einschätzung der Leistungsfähigkeit durchgeführt. Bei ca. 20 % der Patienten wurde ein signifikanter Muskelmasseverlust nach den Kriterien der Sarkopenie festgestellt. Diese Patienten hatten zusätzlich eine signifikant niedrigere linksventrikuläre Ejektionsfraktion (LVEF), eine reduzierte Arm- und Beinkraft sowie Leistungsfähigkeit, gemessen mittels Spiroergometrie, 6-Minuten- und 4 -Meter-Gehtest. In der multivariaten logistischen Regressionsanalyse konnte gezeigt werden, dass der Verlust an Muskelmasse einen unabhängigen Faktor darstellt, um eine verminderte Leistungsfähigkeit in der Spiroergometrie vorherzusagen. Zur Messung hämodynamischer Veränderungen (P 2) fand die Finapres-Methode Anwendung. Hierbei wurden in einer Pilotstudie bei 37 Patienten mit chronischer Herzinsuffizienz sowie bei 43 Patienten mit bösartigen Tumorerkrankungen und 18 gesunden Kontrollen nicht-invasiv kardiale Funktionsparameter, wie das Cardiac Output (CO), das Schlagvolumen (SV) und die maximale Druckanstiegsgeschwindigkeit im linken Ventrikel (dP/dtmax), gemessen. Es zeigte sich, dass bei allen Patienten mit Hilfe der benutzten Methode die Zielparameter erhoben werden konnten und dabei im Wesentlichen den Erwartungswerten entsprachen. In der dritten Arbeit (P 3) wurden zur objektiven Einschätzung des Risikoverhaltens bei 75 Patienten mit chronischer Herzinsuffizienz Cotininlevel mit Hilfe eines Chemilumineszenz-Immunoassays gemessen und mit den subjektiven Aussagen der Patienten hinsichtlich ihrer Übereinstimmung verglichen. Dabei wichen die Ergebnisse von 10 Patienten (16,9 %) von ihren anamnestisch erhobenen Aussagen ab. Bei der Kontrollgruppe ergaben sich keine Diskrepanzen. Schlussfolgerung: Zusammenfassend lässt sich sagen, dass der Muskelmasseverlust bei Patienten mit chronischer Herzinsuffizienz häufig als Komorbidität auftritt. Die nicht-invasive Messung kardialer Funktionsparameter ermöglicht eine einfache Erfassung hämodynamischer Funktionen und auch die Methode der Cotininbestimmung stellt ein einfaches Analyseverfahren des Rauchverhaltens im klinischen Alltag dar, wichtig um Risikoprofile von Patienten besser einschätzen und somit mögliche Therapien schnellstmöglich einleiten zu können.Introduction: Heart failure is a high prevalence disease with poor prognosis and is often accompanied by co-morbidities that influence the patients’ state of health. For these reasons, research into heart failure is very important. In our study, we sought to evaluate co-morbidities such as muscle wasting, the reliability of self-reported smoking behaviour as a major cardiac risk factor and hemodynamic changes in patients with chronic heart failure. Methods and results: Loss of muscle mass and function (P 1), so-called sarcopenia, is a well-known problem in geriatric patients. This condition was assessed in 200 patients by evaluating muscle mass using dual energy X-ray absorptiometry. Additional tests were performed to estimate the patients’ exercise capacity. Significant muscle loss, according to the criteria of sarcopenia, was diagnosed in nearly 20 % of the subjects. Patients also had a significantly lower left ventricular ejection fraction, lower values for handgrip, quadriceps strength and functional capacity, measured by treadmill performance, 6-minute and 4-metre walk test. Multivariate logistic regression analysis indicated muscle wasting as an independent predictor for lower exercise capacity in treadmill performance. To measure hemodynamic changes (P 2), the finapres method was used. Cardiac functional parameters like cardiac output (CO), stroke volume (SV) and the maximal rate of pressure rise during isovolumic contraction (dP/dtmax) were analysed in 37 patients with chronic heart failure, 43 cancer patients and 18 healthy controls. With this method, all target parameters could be readily assessed and complied with the expected values. In the third article (P 3), serum cotinine levels were analysed in 75 patients with chronic heart failure by chemiluminescence immunoassay to estimate self-reported and objective smoking behaviour. Self-reported smoking behaviour did not correspond to the serum cotinine level in 10 (16.9 %) patients with chronic heart failure. No difference was evident in control subjects. Conclusion: Muscle loss is a frequent co-morbidity among patients with chronic heart failure. Non-invasive evaluation of cardiac parameters and serum cotinine measurements are manageable tasks in clinical routine to obtain information about cardiac performance and smoking behaviour. Significantly, these results are important in making an estimate of patients risk and to initiate effective therapy