Table 1.

Skeletal muscle abnormalities in Heart Failure (HF).

Author, yr (#)	Population character	Key measurement	Outcome & Conclusion
Mancini et al., 1988 [33]	HF & age matched healthy control male (~54 yr)	HF:PeakVO2 13.6±5ml/min/kg In vivo P31-NMR	Lower leg muscle mass loss in HF Calf metabolic abnormality part due to muscle atrophy During Exercise Pi/PCr: HF >>Control Recovery time post Ex: HF> control Impaired metabolic profile suggest intrinsic changes not only due to muscle loss
Southern et al., 2015 [54]	HF& age matched Control (~65 yr)	near-infrared spectroscopy	Oxidative capacity lower in HF & Exercise training improved oxidative capacity only in control, suggested reduced oxidative capacity and impaired training adaptation in HF
Mancini et al., 1994, [56]	HF & Control (~58yr)	Ventilatory capacity: progressive isocapnic hyperpnea respiratory muscle deoxygenation near-infrared spectroscopy	Reduced respiratory ventilator capacity without respiratory muscle deoxygenation in HF
Wiener et al., 1986 [57]	HF & age matched control (~60yr)	Forearm blood flow with plethysmography Metabolism: 31P-NMR	Forearm blood flow was similar but increased Pi/PCr upon exercise suggested abnormal metabolism in HF was not due to decreased muscle blood flow rather intrinsic changes in mitochondria or substrate utilization
Mancini et al., 1989 [58]	HF& age matched control (~57yr)	31P NMR: Pi/PCr and PH changes In vitro muscle biopsy: enzyme activity fiber type	HF fiber shift to increased fast, glycolytic type IIb fibers; decreased fatty acid oxidation enzyme activity; 31P NMR also shown higher Pi/PCr; No correlation between Pi/PCr to VO2 and enzyme activity suggested intrinsic changes not due to metabolic response (Pi/PCr changes)
Toth et al., 2012 [87]	HF & Control, age and physical activity matched	18wks resistance training (RE) Muscle biopsy, in vitro analysis	Larger but fewer mitochondria per fiber without difference in content between HF and control; No difference in mitochondria enzyme activity and mRNA level of cytochrome oxidase RE increased mitochondrial transcription factor A and muscle strength for both HF and control, but did not alter mitochondrial size/content, enzyme or transcriptional regulator
Middlekauff et al., 2013[93]	HF & Control (~50 yr, peakVO2 11.6ml/kg/min)	Muscle biopsy & in vitro biochemistry analysis: fiber typing & mitochondira enzyme activity	HF fibers shift to fast twitch; no difference in vascular index or many of mitochondrial enzyme activities; clonidine revealed no impact for HF suggested skeletal myopathy is not caused by neuroendocrine disuse
Zizola et al., 2015 [88]	Myocardial infarction induced mice	In vitro muscle biopsy: fiber typing & enzyme activity assay; ATP content	Muscle dysfunction associated with impaired PPARδ signaling; upon treating MI mice with PPARδ agonist corrected diminished oxidative capacity and FA metabolism (CPT1) and improved exercise capacity
Schrepper et al., 2012 [94]	Pressure overload hypertrophy in rat heart	In vitro assay form muscle biopsy: Isolation of fresh mitochondria mRNA and protein assay	Complex I &II early increase and the later decline (I, II & III) in respiratory capacity not due to differences in gene expression or supercomplex assembly.
Dai et al., 2011 [118]	AngII induced cardiomyopathy in mice treated with SS-31	Flow cytometric access MitoSOX and DCFDA signal	SS-31 reduced AngII induced ROS signal (mitochondrial superoxide and total cellular ROS)
Kitzman et al., 2014 [131]	HF with preserved ejection fraction (HFpEF)	Peak VO2 Fiber type capillary-to-fiber ratio	Reduced type I fiber & capillary to fiber ratio contribute to exercise intolerance among HF