Commentary: Size and margin do matter, but is it the whole story? Beckers, Paul A.J.; Berzenji, Lawek; Van Schil, Paul E.
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
April 2019, 2019-04-00, 20190401, Letnik:
157, Številka:
4
Journal Article
Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties ...in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.
Up to 66% of patients show local pulmonary disease progression after pulmonary metastasectomy. Regional treatment with isolated lung perfusion (ILuP) may improve local control with minimal systemic ...adverse effects. The aims of this study were to evaluate local and distant control after ILuP, determine the effect on overall survival compared with historical controls, and confirm the safety and feasibility of ILuP.
A total of 107 patients with resectable pulmonary metastases of colorectal carcinoma, osteosarcoma, and soft-tissue sarcoma were included in a prospective phase II study of pulmonary metastasectomy combined with ILuP with 45 mg melphalan at 37°C. Local and distant control, overall survival, lung function, and 90-day mortality and morbidity were monitored.
We report 0% mortality, low morbidity, and no long-term pulmonary toxicity. For colorectal carcinoma, median time to local pulmonary progression, median time to progression, and median survival time were 31, 14, and 78 months, respectively. Median time to local progression was not reached for sarcoma, whereas median time to progression and median survival time were 13 and 39 months, respectively. The 5-year disease-free rate and pulmonary progression-free rate were 26% and 44% for colorectal carcinoma and 29% and 63% for sarcoma, respectively.
ILuP with melphalan combined with metastasectomy is feasible and safe. Compared with historical controls, favorable results were obtained in this phase II study for local control. Further evaluation of locoregional lung perfusion techniques with other chemotherapeutic drugs is warranted.
Dipeptidyl peptidase 4 (DPP4) is a cell surface protease that has been reported to play a role in glucose homeostasis, cancer, HIV, autoimmunity, immunology and inflammation. A role for DPP4 in ...ischemia-reperfusion injury (IRI) in the heart has been established. Dipeptidyl peptidase 4 inhibition (DPP4i) appeared to decrease infarct size, improves cardiac function and promotes myocardial regeneration. Lung ischemia reperfusion injury is caused by a complex mechanism in which macrophages and neutrophils play an important role. Generation of reactive oxygen species (ROS), uncoupling of nitric oxide synthase (NOS), activation of nuclear factor-κB (NF-κB), activation of nicotinamide adenine dinucleotide phosphate metabolism, and generation of pro-inflammatory cytokines lead to acute lung injury (ALI). In this review we present the current knowledge on DPP4 as a target to treat IRI in the lung. We also provide evidence of the roles of the DPP4 substrates glucagon-like peptide 1 (GLP-1), vasoactive intestinal peptide (VIP) and stromal cell-derived factor-1α (SDF-1α) in protection against oxidative stress through activation of the mitogen-activated protein kinase (MAPK) 1/2 and phosphatidylinositol 3'-kinase (PI3K)/Akt signal transduction pathways.
Aerobic interval training (AIT) and aerobic continuous training (ACT) both improve physical fitness (peak VO2) in coronary artery disease patients. However, little is known about the long-term ...effects of AIT and ACT on peak VO2 and exercise adherence.
This study is a randomized clinical multicenter trial.
In total, 163 patients were assessed after 12 weeks of AIT or ACT and 12 months after their enrollment. Physical fitness and physical activity measures served as the primary outcomes, and peripheral endothelial function, cardiovascular risk factors and quality of life (QoL) served as the secondary outcomes.
Twenty-six patients dropped out during the intervention; 11 were lost during the follow-up period. Dropouts (n = 37) consisted of more women (p = 0.001) compared to completers (n = 163). Physical fitness (VO2, heart rate and workload at peak and at thresholds) and physical activity (steps, active energy expenditure kcal, physical activity duration minutes) were preserved at the 1-year follow-up (p-time > 0.05) after both AIT and ACT (p-interaction > 0.05). Forty percent of patients showed increased peak VO2, 52% showed increased active energy expenditure and 91.2% met the recommended levels of 150 minutes/week of moderate physical activity (p-group > 0.05). Further, peripheral endothelial function, QoL and cardiovascular risk factors, except systolic blood pressure (p-time < 0.05), remained stable (p-time > 0.05) after both AIT and ACT (p-interaction > 0.05).
The short-term improvements of center-based AIT and ACT on physical fitness, physical activity, peripheral endothelial function, cardiovascular risk factors and QoL are sustained after a 1-year follow-up period. The majority of patients (>90%) met the recommended physical activity levels of 150 minutes/week.
Iron deficiency (ID) is linked to reduced aerobic exercise capacity and poor prognosis in patients with heart failure (HF) with reduced ejection fraction (HFrEF); however, data for HF with preserved ...ejection fraction (HFpEF) is scarce. We assessed the relationship between iron status and diastolic dysfunction as well as aerobic exercise capacity in HFpEF, and the contribution of iron status to patient phenotyping.
Among 180 patients with HFpEF (66% women; median age, 71 years) recruited for the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx-Clin) trial, baseline iron status, including iron, ferritin, and transferrin saturation, was analyzed (
= 169) in addition to exercise capacity (peak oxygen uptake peak V̇O
) and diastolic function (E/e'). ID was present in 60% of patients and was more common in women. In multivariable linear regression models, we found that diastolic function and peak V̇O
were independently related to iron parameters; however, these relationships were present only in patients with HFpEF and ID E/e' and iron: β-0.19 (95% confidence interval -0.32, -0.07),
= 0.003; E/e' and transferrin saturation: β-0.16 (-0.28, -0.04),
= 0.011; peak V̇O
and iron: β 3.76 (1.08, 6.44),
= 0.007; peak V̇O
and transferrin saturation: β 3.58 (0.99, 6.16),
= 0.007. Applying machine learning, patients were classified into three phenogroups. One phenogroup was predominantly characterized by the female sex and few HFpEF risk factors but a high prevalence of ID (86%,
< 0.001 vs. other phenogroups). When excluding ID from the phenotyping analysis, results were negatively influenced.
Iron parameters are independently associated with impaired diastolic function and low aerobic capacity in patients with HFpEF and ID. Patient phenotyping in HFpEF is influenced by including ID.
www.ClinicalTrials.gov, identifier NCT02078947.
Background:
Exercise training improves VO
2
peak in heart failure with reduced ejection fraction (HFrEF), but the effect is highly variable as it is dependent on peripheral adaptations. We evaluated ...changes in plasma-derived miRNAs by acute and chronic exercise to investigate whether these can mechanistically be involved in the variability of exercise-induced adaptations.
Methods:
Twenty-five male HFrEF patients (left ventricular ejection fraction < 40%, New York Heart Association class ≥ II) participated in a 15-week combined strength and aerobic training program. The effect of training on plasma miRNA levels was compared to 21 male age-matched sedentary HFrEF controls. Additionally, the effect of a single acute exercise bout on plasma miRNA levels was assessed. Levels of 5 miRNAs involved in pathways relevant for exercise adaptation (miR-23a, miR-140, miR-146a, miR-191, and miR-210) were quantified using RT-qPCR and correlated with cardiopulmonary exercise test (CPET), echocardiographic, vascular function, and muscle strength variables.
Results:
Expression levels of miR-146a decreased with training compared to controls. Acute exercise resulted in a decrease in miR-191 before, but not after training. Baseline miR-23a predicted change in VO
2
peak independent of age and left ventricular ejection fraction (LVEF). Baseline miR-140 was independently correlated with change in load at the respiratory compensation point and change in body mass index, and baseline miR-146a with change in left ventricular mass index.
Conclusion:
Plasma-derived miRNAs may reflect the underlying mechanisms of exercise-induced adaptation. In HFrEF patients, baseline miR-23a predicted VO
2
peak response to training. Several miRNAs were influenced by acute or repeated exercise. These findings warrant exploration in larger patient populations and further mechanistic
in vitro
studies on their molecular involvement.
Exercise training is a powerful adjunctive therapy in patients with heart failure with reduced ejection fraction (HFrEF), but ca. 55% of patients fail to improve VO2peak. We hypothesize that ...circulating microRNAs (miRNAs), as epigenetic determinants of VO2peak, can distinguish exercise responders (ER) from exercise non-responders (ENR).
We analysed 377 miRNAs in 18 male HFrEF patients (9 ER and 9 ENR) prior to 15 weeks of exercise training using a miRNA array. ER and ENR were defined as change in VO2peak of >20% or <6%, respectively. First, unsupervised clustering analysis of the miRNA pattern was performed. Second, differential expression of miRNA in ER and ENR was analysed and related to percent change in VO2peak. Third, a gene set enrichment analysis was conducted to detect targeted genes and pathways. Baseline characteristics and training volume were similar between ER and ENR. Unsupervised clustering analysis of miRNAs distinguished ER from ENR with 83% accuracy. A total of 57 miRNAs were differentially expressed in ENR vs. ER. A panel of seven miRNAs up-regulated in ENR (Let-7b, miR-23a, miR-140, miR-146a, miR-191, miR-210, and miR-339-5p) correlated with %changeVO2peak (all P < 0.05) and predicted ENR with area under the receiver operating characteristic curves ≥0.77. Multiple pathways involved in exercise adaptation processes were identified.
A fingerprint of seven miRNAs involved in exercise adaptation processes is highly correlated with VO2peak trainability in HFrEF, which holds promise for the prediction of training response and patient-targeted exercise prescription.
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