Key result
Cardiac resynchronization therapy over 6 months improved VE/VCO2 slope (41.6 vs 39.1, P=0.012) and skeletal muscle capillary density (4.5% vs 7.7%, P=0.002) without reducing systemic inflammation.
Why the study?
Does cardiac resynchronization therapy improve skeletal muscle pathology, inflammation, and exercise capacity in patients with symptomatic heart failure?
Cohort (n=21)
Does cardiac resynchronization therapy improve skeletal muscle pathology, inflammation, and exercise capacity in patients with symptomatic heart failure?
Cardiac resynchronization therapy improves exercise capacity and skeletal muscle capillary density in heart failure patients, but does not reverse systemic inflammation or skeletal muscle ultrastructural pathology.
CRT was associated with improved exercise capacity and muscle capillarization in HF without affecting inflammation; hypothesis-generating and needs randomized confirmation.
AIMS: We evaluated the effects of cardiac resynchronization therapy (CRT) on skeletal muscle pathology and inflammation in patients with heart failure. METHODS AND RESULTS: Stable patients (n = 21, 14 males, mean age 70 ± 7 years) with symptomatic heart failure (mean left ventricular ejection fraction 24 ± 6%) and an indication for CRT were included. Ergospirometry, skeletal muscle open biopsy, and blood sampling were performed prior to implantation and after 6 months of CRT. After CRT there was a reduction in both left ventricular end-diastolic diameter (LVEDD; 6.8 ± 0.8 vs. 6.3 ± 0.7 cm, P < 0.001) and native QRS duration (D) minus biventricular paced QRSD (172.9 ± 23 vs. 136.3 ± 23 ms, P ≤ 0.001). These changes were associated with an increase in peak slope oxygen uptake (consumption) (VO₂) (13.3 ± 2.2 vs. 14.5 ± 2.6 mL/kg/min, P = 0.07) and an improvement in the minute ventilation/carbon dioxide production slope (VE/VCO₂) slope (41.6 ± 7.4 vs. 39.1 ± 5.6, P = 0.012). There were no statistically significant changes in levels of pro-inflammatory cytokines, in mediators of mitochondrial biosynthesis or skeletal muscle pathology, except for an increase in skeletal muscle capillary density (4.5 ± 2.4 vs. 7.7 ± 3.3%, P = 0.002). Both the reduction of QRS duration and the increase in peak VO₂ correlated significantly with the change in mitochondrial density (r = 0.57, P = 0.008 and r = 0.54, P = 0.027, respectively). CONCLUSION: Cardiac resynchronization therapy, with improved functional status and reduced LVEDD resulted in increased peak VO₂, improvement in VE/VCO₂ slope and capillary density in skeletal muscle, with no reduction in systemic pro-inflammatory cytokines, increase in intramuscular levels of mediators of mitochondrial biosynthesis or improvement in skeletal muscle ultrastructure per se. ClinicalTrials.gov Identifier: NCT01019915.
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Larsen et al. (2013) conducted a cohort in symptomatic heart failure (n=21). Cardiac resynchronization therapy (CRT) vs. Baseline (prior to implantation) was evaluated on minute ventilation/carbon dioxide production (VE/VCO2) slope (p=0.012). Cardiac resynchronization therapy over 6 months improved VE/VCO2 slope (41.6 vs 39.1, P=0.012) and skeletal muscle capillary density (4.5% vs 7.7%, P=0.002) without reducing systemic inflammation.
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