The Effect of Exercise Modalities on Walking Capacity in Patients With Intermittent Claudication: A NETWORK META-ANALYSIS.

INTRODUCTION: Despite extensive research on the effect of supervised exercise therapy on walking performance in patients with symptomatic peripheral arterial disease (PAD), it remains unclear which training modality provides the greatest improvement in walking capacity. The objective of this study was to compare the effect of different types of supervised exercise therapy on walking capacity in individuals with symptomatic PAD. METHODS: A random-effect network meta-analysis was performed. The following databases were searched from January 1966 to April 2021: SPORTDiscus, CINAHL, MEDLINE, AMED, Academic Search Complete and, Scopus. Trials had to include at least one type of supervised exercise therapy for patients with symptomatic PAD, with an intervention lasting ≥2 wk with ≥5 training sessions, and an objective measure of walking capacity. RESULTS: Eighteen studies were included for a total sample of 1135 participants. Interventions duration ranged from 6-24 wk and included aerobic exercise (treadmill walking, ergometer, and Nordic walking), resistance training (lower and/or upper body), a combination of both, and underwater exercise. Results showed that combined training improved treadmill walking capacity to a comparable extent to aerobic walking (+122.0 [24.2-219.8] m vs +106.8 [34.2-179.4] m), but with a larger effect size (1.20 [0.50-1.90] vs 0.67 [0.22-1.11]). Similar results were observed for the 6-min walk distance, with combined training being the most promising modality (+57.3 [16.2-98.5] m), followed by underwater training (+56.5 [22.4-90.5] m) and aerobic walking (+39.0 [12.8-65.1] m). CONCLUSION: While not statistically superior to aerobic walking, combined exercise seems to be the most promising training modality. Aerobic walking and underwater training also improved walking capacity for patients with symptomatic PAD.

Doppler Renal Resistance Index for the Prediction of Response to Passive Leg-Raising Following Cardiac Surgery.

PURPOSE: Doppler-based renal resistance index (RI) can be measured at the bedside of critically ill patients. This study was designed to assess if the RI predicted an increase in cardiac output (CO) following passive leg-raising (PLR) in patients admitted to the intensive care unit after cardiac surgery. METHODS: During this single center prospective study, Doppler assessment of RI and measurements of CO using the thermodilution method were performed, after surgery, in the intensive care unit before and after PLR. A positive response to PLR was defined as a ≥10% increase in CO. RESULTS: We included 30 patients. The mean RI was higher before (0.694 ±0.069) than after PLR (0.679 ± 0.069) (P = .02) with a median change of -0.012 (IQR: -0.042;0.000). Following PLR, 9 patients (30%) had a >10% increase in CO. In patients with a positive PLR response, the decrease in the RI during PLR was more pronounced than in patients who did not respond to PLR (PLR ± 0.042 (IQR: -0.051; -0.040) vs PLR ± -0.008 (IQR: -0.032; 0.015) (P = .004). There was a significant negative association between RI change in response to PLR and a 10% increase in CO following PLR (OR: 1.63 (CI:1.07-2.47) (P = .02) per -0.01 change). CONCLUSION: An increase in CO following PLR was associated with a significant decrease in RI. Variations of RI in response to PLR should be further studied as a tool to predict fluid responsiveness. However, their clinical utility could be limited by the small magnitude of the variations.

Apolipoprotein B antisense inhibition--update on mipomersen.

Dyslipidemia is one of the main risk factors leading to cardiovascular disease (CVD). The standard of therapy, administration of statins, in conjunction with lifestyle and habit changes, can improve high cholesterol levels in the majority of patients. However, some patients with familial hypercholesterolemia (FH) need low-density-lipoprotein cholesterol (LDL-C) apheresis, as the available medications fail to reduce LDL-C levels sufficiently even at maximum doses. Intense research on cholesterol reducing agents and rapid progress in drug design have yielded many approaches that reduce cholesterol absorption or inhibit its synthesis. Antisense oligonucleotides (ASOs) targeting the production of apolipoprotein B-100 (apoB-100), inhibitors of proprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein inhibitors, squalene synthase inhibitors, peroxisome proliferator-activated receptor agonists, and thyroid hormone receptor agonists are some of the evolving approaches for lipid-lowering therapies. We provide an overview of the apoB ASO approach and its potential role in the management of dyslipidemia. Mipomersen (ISIS-301012, KYNAMRO™) is a synthetic ASO targeting the mRNA of apoB-100, which is an essential component of LDL particles and related atherogenic lipoproteins. ASOs bind to target mRNAs and induce their degradation thereby resulting in reduced levels of the corresponding protein levels. Mipomersen has been investigated in different indications including homozygous and heterozygous FH, as well as in high-risk hypercholesterolemic patients. Recent phase II and III clinical studies have shown a 25-47% reduction in LDL-C levels in mipomersen-treated patients. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for high-risk populations.