Exercise Intervention to Improve Functional Capacity in Older Adults After Acute Coronary Syndrome

More than one-half of patients admitted for acute coronary syndrome (ACS) are age $70 years. Mobility limitations and sedentary behavior are common in older ACS patients and contribute to high risk of recurrence and mortality (1). Although older ACS patients may benefit the most from participation in exercise-based cardiac rehabilitation/secondary prevention programs (CR/SP), they are less likely to participate in such programs (2). Whether an early, individualized, and low-cost physical activity (PA) intervention including a few supervised sessions and a home-based program might be feasible and effective for improving functional capacity in this high-risk and undertreated population is unknown. The HULK (Physical Activity Intervention for Patients With Reduced Physical Performance After Acute Coronary Syndrome; NCT03021044) trial is a multicenter, randomized clinical trial. A detailed study outline and statistical plan have been previously published (3). Inclusion criteria were age$70 years, hospitalization for ACS, and Short Physical Performance Battery (SPPB) score between 4 and 9 at the inclusion visit (30 5 days after hospital discharge). The SPPB is a scale that combines gait speed, chair stand, and balance tests. It ranges from 0 (worst) to 12 (best) and has predictive validity for mortality (4). Participants were randomized to usual care and health education (control group) or usual care and PA intervention (intervention group). The control group received a 20-min session and a detailed brochure stressing the importance of PA in cardiovascular health. The PA intervention consisted of four supervised sessions (1, 2, 3, and 4 months after hospital discharge), combined with an individualized home-based PA program. Centerbased sessions included a moderate standardized treadmill-walk, strength, and balance exercises (3). After the practice sessions, patients received a tailored PA home program (3). Weekly energy expenditure from PA was determined by a selfreported 7-day physical activity recall (kcal/week), and objectively measured by wearing an accelerometer (min/week). The primary endpoint was the 6- month SPPB. Secondary endpoints were 1-year SPPB and time engaged in PA. From January 2017 to April 2018, 235 patients were randomized (n ¼ 117, control group; n ¼ 118, intervention group). The median age was 76 (interquartile range [IQR]: 73 to 81) years, and 23% were female. Before the hospitalization, light and moderateintensive PA was performed by 66% and 14% of patients, respectively. Baseline characteristics, as well as baseline SPPB value (Figure 1), did not differ between groups. The adherence rates of the PA intervention group to the 1-, 2-, 3-, and 4-month scheduled supervised sessions were 100%, 89%, 85%, and 72%, respectively. The time engaged in PA progressively and significantly increased in the intervention group (Figure 1). At 6 months, the SPPB score was significantly higher in the intervention group (median: 9 [IQR: 8 to 11] vs. 7 [IQR: 5 to 8]; p < 0.001) (Figure 1). This improvement was supported by a significant increase in SPPB components of walking and chair rise (balance remained unchanged). The number of patients showing an increase of at least 1 point in SPPB score was 86 (74%) in the intervention group versus 46 (40%) in the control group (p < 0.001). The SPPB increase was maintained at the 1-year visit (Figure 1) and independent of sex and educational status. Typical CR/SP includes 3 weekly supervised exercise and educational sessions for 12 weeks. Despite the health benefits associated with these interventions, few eligible patients are referred or complete such programs (1). Our novel PA intervention was designed to address this issue. The attendance rate was high (72% [95% confidence interval: 64% to 80%]). The average weekly energy expenditure from PA in the intervention group increased 3.4 times, and SPPB score showed a mean increment of 2.0 points. This finding is notable given that an SPPB improvement of 1.0 point is generally considered a substantial clinically meaningful change (2). In addition, despite the absence of supervised sessions after the sixth month, the achievements were maintained until 1-year visit. If confirmed in future studies, our PA intervention model might help to mitigate the challenges related to limited health care resources and might increase the number of older adults receiving CR/SP

Contrast associated acute kidney injury and mortality in older adults with acute coronary syndrome: A pooled analysis of the fraser and hulk studies

Whether contrast-associated acute kidney injury (CA-AKI) is only a bystander or a risk factor for mortality in older patients undergoing percutaneous coronary intervention (PCI) is not well understood. Data from FRASER (NCT02386124) and HULK (NCT03021044) studies have been analysed. All patients enrolled underwent coronary angiography. The occurrence of CA-AKI was defined based on KDIGO criteria. The primary outcome of the study was to test the relation between CA-AKI and 3-month mortality. Overall, 870 older ACS adults were included in the analysis (mean age 78 ± 5 years; 28% females). CA-AKI occurred in 136 (16%) patients. At 3 months, 13 (9.6%) patients with CA-AKI died as compared with 13 (1.8%) without it (p < 0.001). At multivariable analysis, CA-AKI emerged as independent predictor of 3-month mortality (HR 3.51, 95%CI 1.05–7.01). After 3 months, renal function returned to the baseline value in 78 (63%) with CA-AKI. Those without recovered renal function (n = 45, 37%) showed an increased risk of mortality as compared to recovered renal function and no CA-AKI subgroups (HR 2.01, 95%CI 1.55–2.59, p = 0.009 and HR 2.71, 95%CI 1.45–5.89, p < 0.001, respectively). In conclusion, CA-AKI occurs in a not negligible portion of older MI patients undergoing invasive strategy and it is associated with short-term mortality

Adherence to Gluten-Free Diet Restores Alpha Diversity in Celiac People but the Microbiome Composition Is Different to Healthy People

Celiac disease (CD) is an autoimmune disease with the destruction of small intestinal villi, which occurs in genetically predisposed individuals. At the present moment, a gluten-free diet (GFD) is the only way to restore the functionality of gut mucosa. However, there is an open debate on the effects of long-term supplementation through a GFD, because some authors report an unbalance in microbial taxa composition. Methods: For microbiome analysis, fecal specimens were collected from 46 CD individuals in GFD for at least 2 years and 30 specimens from the healthy controls (HC). Data were analyzed using an ensemble of software packages: QIIME2, Coda-lasso, Clr-lasso, Selbal, PICRUSt2, ALDEx2, dissimilarity-overlap analysis, and dysbiosis detection tests. Results: The adherence to GFD restored the alpha biodiversity of the gut microbiota in celiac people but microbial composition at beta diversity resulted as different to HC. The microbial composition of the CD subjects was decreased in a number of taxa, namely Bifidobacterium longum and several belonging to Lachnospiraceae family, whereas Bacteroides genus was found to be more abundant. Predicted metabolic pathways among the CD bacterial communities revealed an important role in tetrapyrrole biosynthesis. Conclusions: CD patients in GFD had a non-dysbiotic microbial composition for the crude alpha diversity metrics. We found significant differences in beta diversity, in certain taxon, and pathways between subjects with inactive CD in GFD and controls. Collectively, our data may suggest the development of new GFD products by modulating the gut microbiota through diet, supplements of vitamins, and the addition of specific prebiotics

Physical activity intervention for elderly patients with reduced physical performance after acute coronary syndrome (HULK study): Rationale and design of a randomized clinical trial

Background: Reduced physical performance and impaired mobility are common in elderly patients after acute coronary syndrome (ACS) and they represent independent risk factors for disability, morbidity, hospital readmission and mortality. Regular physical exercise represents a means for improving functional capacity. Nevertheless, its clinical benefit has been less investigated in elderly patients in the early phase after ACS. The HULK trial aims to investigate the clinical benefit of an early, tailored low-cost physical activity intervention in comparison to standard of care in elderly ACS patients with reduced physical performance. Design: HULK is an investigator-initiated, prospective multicenter randomized controlled trial (NCT03021044). After successful management of the ACS acute phase and uneventful first 1 month, elderly (≥70 years) patients showing reduced physical performance are randomized (1:1 ratio) to either standard of care or physical activity intervention. Reduced physical performance is defined as a short physical performance battery (SPPB) score of 4-9. The early, tailored, low-cost physical intervention includes 4 sessions of physical activity with a supervisor and an home-based program of physical exercise. The chosen primary endpoint is the 6-month SPPB value. Secondary endpoints briefly include quality of life, on-treatment platelet reactivity, some laboratory data and clinical adverse events. To demonstrate an increase of at least one SPPB point in the experimental arm, a sample size of 226 patients is needed. Conclusions: The HULK study will test the hypothesis that an early, tailored low-cost physical activity intervention improves physical performance, quality of life, frailty status and outcome in elderly ACS patients with reduced physical performance

Impact of postdilatation on performance of bioresorbable vascular scaffolds in patients with acute coronary syndrome compared with everolimus-eluting stents: A propensity score-matched analysis from a multicenter “real-world” registry

Background: Safety and efficacy of bioresorbable vascular scaffolds (BRS) and the role of postdilatation on outcome in acute coronary syndrome (ACS) patients compared with those of everolimus-eluting stents (EES) remain unknown. The aim of the study is to compare the safety and efficacy of BRS with EES in ACS and to investigate the role of BRS postdilatation. Methods: Consecutive ACS patients undergoing BRS implantation in 8 centers were com­pared with those with EES before and after propensity score matching. Major adverse cardiac event (MACE), myocardial infarction, and target lesion revascularization (TLR) were the primary endpoint. Sensitivity analysis was performed according to postdilatation after BRS implantation. We enrolled 303 BRS and 748 EES patients; 215 from each group were com­pared after matching, and 117 (55.2%) BRS patients were treated with postdilatation. Results: After a median follow-up of 24.0 months, MACE rates were higher in BRS patients than in EES patients (9.3% vs. 4.7%, p < 0.001), mainly driven by TLR (6.1% vs. 1.9%, p < 0.001). Stent thrombosis increased in the BRS group (2.8% vs. 0.9%, p = 0.01). How­ever, after sensitivity analysis, MACE rates in BRS patients with postdilatation were signifi­cantly lower than in those without, comparable to EES patients (6.0% vs. 12.6% vs. 4.7%, p < 0.001). The same trend was observed for TLR (3.4% vs. 8.4% vs. 1.9%, p < 0.001). Stent thrombosis rates were higher in both the BRS groups than in EES patients (2.6% vs. 3.2% vs. 0.9%, p = 0.045). Conclusions: Postdilatation appears effective when using BRS in ACS patients. MACE rates are comparable to those of EES, although scaffold thrombosis is not negligible. Randomized prospective studies are required for further investigation

Investigation of Multiple Susceptibility Loci for Inflammatory Bowel Disease in an Italian Cohort of Patients

BACKGROUND: Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. METHODS: Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. RESULTS: The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10(-6)). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10(-5)). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated. CONCLUSIONS: We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes

Frailty in patients admitted to hospital for acute coronary syndrome: When, how and why?

Frailty is an issue of paramount importance for cardiologists, because of the aging of patients admitted to hospital for acute coronary syndrome (ACS) and the straight relationship between aging and frailty. Several tools have been provided in this setting, in order to objectively assess frailty status, but important questions are still unsolved. There are conflicting data about a unique definition of frailty in subjects with cardiovascular diseases, the timing to perform a frailty evaluation in the context of an acute myocardial infarction, the mean to assess frailty in these patients and the usefulness of the information derived from the frailty assessment. Frailty results from the analysis of several items and a multidomain evaluation including laboratory values, clinical data and physical performance assessment is required for a comprehensive frailty assessment. However, regardless of the frailty tool, the prevalence of frailty in older ACS patients is high and it could add important information to the decision-making process about invasive strategy, the multivessel disease management, dual antiplatelet therapy and secondary prevention programs. The present overview tries to summarize the current knowledge about the definition and prevalence of frailty in older adults admitted to hospital for ACS, suggesting how frailty assessment may improve the management of older ACS patients

Dual Antiplatelet Therapy in Patients with Glucose-6-Phosphate Dehydrogenase Deficiency undergoing PCI with Drug-Eluting Stents.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. In patients with G6PD deficiency, the use of aspirin is controversial, since past studies have reported a potential risk of haemolysis related to its administration, even at low doses. More recent publications have shown that low-dose aspirin administration is safe in these patients. At the same time, no authors have previously reported more than single cases regarding low-dose aspirin treatment in patients with G6PD deficiency undergoing percutaneous coronary intervention (PCI), and most physicians are still sceptical about aspirin administration in these patients. In this paper, we report a case series of five patients with G6PD deficiency receiving PCI with drug-eluting stents (DES) and treatment with dual antiplatelet therapy (DAPT) containing low-dose aspirin, without clinical complications. Moreover, we discuss our internal protocol for managing these patients and provide an overview of the available data