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

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

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

Rationale and Design of the PARTHENOPE Trial: A Two-by-Two Factorial Comparison of Polymer-Free vs. Biodegradable-Polymer Drug-Eluting Stents and Personalized vs. Standard Duration of Dual Antiplatelet Therapy in All-Comers Undergoing PCI.

BACKGROUND Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 13 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the non-inferiority between stents with respect to a device-oriented composite endpoint of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI

Fractional flow reserve: Current applications and overview of the available data

Flow fractional reserve (FFR) allows to evaluate the functional significance of coronary artery lesions, through the ratio of the mean coronary artery pressure after the stenosis to the mean aortic pressure during maximum hyperemia. The actual widely accepted cut-off value is 0.80. Below this value a coronary lesion is considered significant and therefore it requires invasive revascularization. Several studies [in particular Fractional Flow Reserve vs Angiography for Multivessel Evaluation 1 (FAME-1) and FAME-2] have shown the relationship between FFR measurement and hard end-points (death, myocardial infarction, and urgent revascularization). Consequently, FFR evaluation represents the cornerstone in the decision-making in intermediate coronary lesions. Recent studies paved the way for further applications of FFR evaluation in complex and tricky clinical settings. In this paper, we perform an overview of the data regarding contemporary application of FFR. In particular, we review the use of FFR in: left main intermediate stenoses, serial stenoses, evaluation after stenting, guidance in coronary artery bypass surgery, and acute coronary syndrome. All the data presented in our overview confirm the essential role of FFR assessment in the daily clinical practice. The shift from "operator-dependent" to "FFR-dependent" evaluation in intermediate coronary artery stenosis is of paramount importance in order to improve the prognosis of our patients, through the discrimination of the functional role of every single coronary stenosis

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

Functional assessment 3.0: From wire through angio to OCT

No abstract availabl