Minimal Clinically Important Differences in 6-Minute Walk Test in Patients With HFrEF and Iron Deficiency.

BACKGROUND: The 6-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: To calculate the minimal clinically important difference (MCID) for change in exercise capacity in the 6MWT in iron-deficient populations with HFrEF. METHODS: In this pooled secondary analysis of the FAIR-HF and CONFIRM-HF trials, mean changes in the 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool (clinical anchor) to derive MCIDs in improvement and deterioration. RESULTS: Of 760 patients included in the 2 trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281 ± 103 meters. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r = 0.31; P < 0.0001) and week 24 (r = 0.43; P < 0.0001). Respective estimates (95% confidence intervals) of MCID in 6MWT at weeks 12 and 24 were 14 meters (5;23) and 15 meters (3;27) for a "little improvement" (vs no change), 20 meters (10;30) and 24 meters (12;36) for moderate improvement vs a "little improvement,", -11 meters (-32;9.2) and -31 meters (-53;-8) for a "little deterioration" (vs no change), and -84 meters (-144;-24) and -69 meters (-118;-20) for "moderate deterioration" vs a "little deterioration". CONCLUSIONS: The MCID for improvement in exercise capacity in the 6MWT was 14 meters-15 meters in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data.

Sarcopenia and cachexia in chronic diseases: from mechanisms to treatment.

Two main manifestations of wasting disorders in chronic disease are cachexia and sarcopenia. Due to shared pathological features, including impairments in systemic inflammatory responses, neurohormonal activity, and metabolic systems, the 2 disorders can present with similar symptoms (tissue depletion, dyspnea, anorexia, asthenia, fatigue, and impaired physical performance). Wasting disorders are associated with reduced quality of life and increased mortality. Cachexia is characterized by systemic tissue depletion with weight loss, and sarcopenia, by skeletal muscle loss accompanied by diminished muscular strength and physical performance. Wasting syndromes can be identified based on clinical criteria as well as with the use of multiple imaging and diagnostic techniques. Additionally, blood biomarkers can be used for diagnosing wasting disorders. In the past decade, intensive research has focused on new therapeutic strategies within a multimodal approach, which embraces nutritional support, physical activity, and targeted pharmacological therapy. Despite some initial promising therapeutic results for selected novel agents, guideline-recommended pharmacotherapy is not yet available for cachexia or sarcopenia. More research is needed to better understand these wasting disorders and learn how to treat them.

Future developments in the MECKI score initiative.

The Metabolic Exercise combined with Cardiac and Kidney Indexes [MECKI) score is a validated prognostic score for heart failure with reduced ejection fraction which combines commonly available clinical and metabolic parameters with two cardiopulmonary exercise test derived prognostic measurements. It has been validated to predict prognosis and to aid clinical decision making and it has been shown to be superior in predicting mortality compared with other commonly used prognostic scores for heart failure. In the future it would be valuable to establish whether the score holds true also in other settings, and in particular in under-represented groups - the elderly, women, and people of different ethnic backgrounds - and in other heart failure syndromes. In future it may be extended to assess its value in the presence of a range of co-morbidities such as chronic obstructive pulmonary disease, pulmonary hypertension and frailty and cachexia as well as in other conditions such as hypertrophic cardiomyopathy, amyloid, asymptomatic left ventricular dysfunction and hypertension. It may also be a candidate end-point for adaptive trials designed to prove an improvement in the MECKI score as an approvable interim end-point whilst larger mortality and morbidity trials are still underway.