Improving exercise capacity and quality of life using non‐invasive heart failure treatments: evidence from clinical trials

Abstract

Endpoints of large‐scale trials in chronic heart failure have mostly been defined to evaluate treatments with regard to hospitalizations and mortality. However, patients with heart failure are also affected by very severe reductions in exercise capacity and quality of life. We aimed to evaluate the effects of heart failure treatments on these endpoints using available evidence from randomized trials. Interventions with evidence for improvements in exercise capacity include physical exercise, intravenous iron supplementation in patients with iron deficiency, and – with less certainty – testosterone in highly selected patients. Erythropoiesis‐stimulating agents have been reported to improve exercise capacity in anaemic patients with heart failure. Sinus rhythm may have some advantage when compared with atrial fibrillation, particularly in patients undergoing pulmonary vein isolation. Studies assessing treatments for heart failure co‐morbidities such as sleep‐disordered breathing, diabetes mellitus, chronic kidney disease and depression have reported improvements of exercise capacity and quality of life; however, the available data are limited and not always consistent. The available evidence for positive effects of pharmacologic interventions using angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, beta‐blockers, and mineralocorticoid receptor antagonists on exercise capacity and quality of life is limited. Studies with ivabradine and with sacubitril/valsartan suggest beneficial effects at improving quality of life; however, the evidence base is limited in particular for exercise capacity. The data for heart failure with preserved ejection fraction are even less positive, only sacubitril/valsartan and spironolactone have shown some effectiveness at improving quality of life. In conclusion, the evidence for state‐of‐the‐art heart failure treatments with regard to exercise capacity and quality of life is limited and appears not robust enough to permit recommendations for heart failure. The treatment of co‐morbidities may be important for these patient‐related outcomes. Additional studies on functional capacity and quality of life in heart failure are required.

Muscle wasting as an independent predictor of survival in patients with chronic heart failure

“…4,34,35 Unfortunately, none of these interventions have been tested in prospective randomized controlled trials of adequate size so far, but smaller trials suggest that exercise training improves quality of life and the distance covered during the 6 min walk test. 12 Taken together, muscle wasting beyond the cut-offs defined to identify sarcopenia identifies a large proportion of patients with HF who have low muscle strength, quality of life, and exercise capacity and who are likely to become frail in that they may be at increased risk of falling, risk of fractures, and hospitalizations. Our data show that these patients are also at two-fold increased risk of death, an effect primarily driven by events in patients with HFrEF.…”

“…high‐calorie nutritional supplements and branched‐chain amino acids), 31–33 and possibly anabolic substances 4,34,35 . Unfortunately, none of these interventions have been tested in prospective randomized controlled trials of adequate size so far, but smaller trials suggest that exercise training improves quality of life and the distance covered during the 6 min walk test 12 …”

“…10 This finding coincides with reduced peripheral blood flow in patients with muscle wasting. 11 Interestingly, mitochondrial energy production can be improved in the skeletal muscle by intravenous iron therapy in patients with iron deficiency, 12 underlining the importance of iron provision for energy production in this system. Treatment of muscle wasting and iron deficiency may provide an interesting means to improve exercise capacity and quality of life, both of which are difficult to increase using guideline -recommended HF treatments.…”

“…Treatment of muscle wasting and iron deficiency may provide an interesting means to improve exercise capacity and quality of life, both of which are difficult to increase using guideline -recommended HF treatments. 12 It has long been established that cardiac cachexia is associated with reduced survival, and this finding is independent of other prognostic factors such as age, reduced peak oxygen consumption, left ventricular ejection fraction (LVEF), or New York Heart Association (NYHA) class. 13 The aim of the present analysis from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) was to test whether skeletal muscle wasting itself carries prognostic information in patients with HF, irrespective of whether HFrEF or HFpEF is present.…”

Low ALT Levels Associated with Poor Outcomes in 8700 Hospitalized Heart Failure Patients

“…Heart failure (HF), either with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), remains a rising global epidemic and a major cause of re-hospitalizations, increased overall (both short- and long-term) mortality, limited exercise capacity, and significantly lower quality of life [ 1 , 2 , 3 , 4 ]. Frailty is a clinical syndrome manifesting as increased vulnerability from age-related decline in physiological reserve and function, leading to a reduced ability to tolerate biological stressors.…”