Association of Intrinsic Capacity with Frailty, Physical Fitness and Adverse Health Outcomes in Community-Dwelling Older Adults.

BACKGROUND: Intrinsic capacity (IC) and frailty are complementary in advancing disability prevention through maintaining functionality. OBJECTIVES: We examined the relationship between IC and frailty status at baseline and 1-year, and evaluated if IC decline predicts frailty onset among robust older adults. The secondary objectives investigated associations between IC, physical fitness and health-related outcomes. DESIGN: Prospective cohort study. SETTING: Community-based assessments. PARTICIPANTS: Older adults aged>55 years, who were independent in ambulation (walking aids permitted). MEASUREMENTS: 5 domains of IC were assessed at baseline: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Composite IC (0-10) was calculated, with higher scores representing greater IC. Frailty status was based on modified Fried criteria, with frailty progression defined as incremental Fried score at 1-year. RESULTS: 809 participants (67.6+6.8 years) had complete data for all 5 IC domains. 489 (60.4%) participants were robust but only 213 (26.3%) had no decline in any IC domain. Pre-frail and frail participants were more likely to exhibit decline in all 5 IC domains (p<0.05), with decremental composite IC [9 (8-9), 8 (6-9), 5.5 (4-7.5), p<0.001] across robust, prefrail and frail. IC was significantly associated with fitness performance, independent of age and gender. Higher composite IC reduced risk for frailty progression (OR=0.62, 95% CI 0.48-0.80), and reduced frailty onset among robust older adults (OR=0.53, 95% CI 0.37-0.77), independent of age, comorbidities and social vulnerability. Participants with higher IC were less likely to experience health deterioration (OR=0.70, 95% CI 0.58-0.83), falls (OR=0.76, 95% CI 0.65-0.90) and functional decline (OR=0.64, 95% CI 0.50-0.83) at 1-year. CONCLUSION: Declining IC may present before frailty becomes clinically manifest, increasing risk for poor outcomes. Monitoring of IC domains potentially facilitates personalized interventions to avoid progressive frailty.

Sex-based outcomes after PCI in highbleeding risk patients: Results from the onyx one clear trial

BACKGROUND: While dual antiplatelet therapy (DAPT) constitutes the cornerstone of post-PCI pharmacotherapy, duration of DAPT in high bleeding risk (HBR) patients has not been fully defined especially with regard to sex. The results from the Onyx ONE Clear trial demonstrated favorable safety and efficacy after PCI with 1-month dual antiplatelet therapy (DAPT) in HBR patients treated with Resolute Onyx drug-eluting stents (DES). We sought to evaluate impact of sex on clinical outcomes in this trial. METHODS: In this prespecified subgroup analysis from Onyx ONE Clear, patients were divided into 2 groups according to sex. Primary endpoint was cardiac death or myocardial infarction (MI) from 1 month to 1 year. RESULTS: A total of 487 female patients (32%) and 1019 males (68%) were free from major ischemic events 1-month after PCI and were transitioned to single antiplatelet therapy.Women were older (p<0.001), had more HBR criteria (p=0.02), and higher rates of moderate/severe calcific lesions (p=0.03) compared to men. Men had higher rates of previous MI (p=0.003), atrial fibrillation (p=0.001), and multivessel coronary artery disease (p<0.001). Clinical outcomes between 1 and 12 months are shown in (Figure) and were similar for males and females except for target vessel revascularization which was greater for males (p=0.04). CONCLUSIONS: In HBR patients treated with Resolute Onyx DES and an abbreviated DAPT course of one month, rates of the primary endpoint of cardiac death or MI between 1 and 12 months were low and did not show any sex-based differences. These data support the use of an abbreviated DAPT regimen in men and women with HBR after PCI with Resolute Onyx DES.

A Non-Controlled Study of a Multi-Factorial Exercise and Nutritional Intervention to Improve Functional Performance and Prevent Frailty Progression in Community-Dwelling Pre-Frail Older Adults.

Background: Preventing frailty is important to avoid adverse health outcomes. Intervention studies have largely focused on frail elderly, although the intermediate pre-frail state may be more amenable to improvement. Objectives: This study aims to assess how physical performance may change among pre-frail elderly enrolled in a pragmatic non-controlled exercise and nutritional intervention programme. Methods: This is a non-controlled study involving a 4-month exercise and nutritional intervention for community dwelling pre-frail older adults. Pre-frailty was defined as the presence of 1 or 2 positive responses on the FRAIL questionnaire, or evidence of weak grip strength (<26kg for males; <18kg for females) or slow gait speed (<0.8m/s) amongst participants who were asymptomatic on FRAIL. Physical performance in flexibility, grip and lower limb strength, endurance, balance, and Short Physical Performance Battery were measured at 3 time-points: baseline, 3-month from recruitment (without intervention), and immediate post-intervention. Repeated measures mixed model analysis was performed to compare physical performance measures across the 3 time-points. Results: 94 pre-frail participants were eligible for intervention, of whom 59 (mean age = 70.9±7.2 years) were ready for the post-intervention review. 21 (35.6%) transitioned to robust phenotype while 32 (54.2%) remained as pre-frail. Significant improvement post-intervention was observed in lower limb strength and power, evident on reduction in time taken for 5 sit-to-stand repetitions (0.46±0.20s, p=0.03). There was no significant change to the other physical performance measures examined. Conclusion: We observed reversibility of pre-frailty, and the benefit of multi-component intervention in improving physical performance of pre-frail older adults. The findings in this non-controlled study will need to be corroborated with future controlled trials.

Frailty Assessment in Community-Dwelling Older Adults: A Comparison of 3 Diagnostic Instruments.

OBJECTIVES: Compare the diagnostic performance of FRAIL against Fried Phenotype and Frailty Index (FI), and identify clinical factors associated with pre-frailty/frailty. DESIGN: Cross-sectional analysis. SETTING: Community-based screenings in Senior Activity Centres, Residents' Corners and Community Centres in northeast Singapore. PARTICIPANTS: 517 community dwelling participants aged >55 years and ambulant independently (with/ without walking aids) were included in this study. Residents of sheltered or nursing homes, and seniors unable to ambulate at least four meters independently were excluded. MEASUREMENTS: The multidomain geriatric screen included assessments for social vulnerability, mood, cognition, sarcopenia and nutrition. Participants completed a battery of physical fitness tests for grip strength, gait speed, lower limb strength and power, flexibility, balance and endurance, with overall physical performance represented by Short Physical Performance Battery (SPPB). Frailty status was assigned on FRAIL, Fried and 35-item FI. RESULTS: Prevalence of frailty was 1.3% (FRAIL) to 3.1% (FI). Pre-frailty prevalence ranged from 17.0% (FRAIL) to 51.2% (FI). FRAIL demonstrated poor agreement with FI (kappa=0.171, p<0.0001), and Fried (kappa=0.194, p<0.0001). A lower FRAIL cut-off ≥1 yielded significantly improved AUC of 0.70 (95%CI 0.55 to 0.86, p=0.009) against Fried, and 0.71 (95%CI 0.55 to 0.86, p=0.008) against FI. All 3 frailty measures were diagnostic of impaired physical performance on SPPB, with AUCs ranging from 0.69 on FRAIL to 0.77 on Fried (all p values <0.01). Prevalence of low socio-economic status, depression, malnutrition and sarcopenia increased significantly, while fitness measures of gait speed, balance, and endurance declined progressively across robust, pre-frail and frail on all 3 frailty instruments (p <0.05). CONCLUSIONS: Our results suggest that different frailty instruments may capture over-lapping albeit distinct constructs, and thus may not be used interchangeably. FRAIL has utility for quick screening, and any positive response should trigger further assessment, including evaluation for depression, social vulnerability and malnutrition.

Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

Intra-procedural monitoring protocol using routine transthoracic echocardiography with backup trans-oesophageal probe in transcatheter aortic valve replacement: a single centre experience.

AIM: The aim of this study is to describe our 9-year experience in transcatheter aortic valve replacement (TAVR) using transthoracic echocardiography (TTE) as a routine intra-procedural imaging modality with trans-oesophageal echocardiography (TEE) as a backup. METHODS AND RESULTS: From January 2008 to December 2017, 1218 patients underwent transfemoral TAVR at our Institution. Except the first 20 cases, all procedures have been performed under conscious sedation, with fluoroscopic guidance and TTE imaging monitoring. Once the TTE resulted suboptimal for final result assessment or a complication was either suspected or identified on TTE, TEE evaluation was promptly performed under general anaesthesia. Only 24 (1.9%) cases required a switch to TEE: 6 cases for suboptimal TTE prosthetic valve leak (PVL) quantification; 12 cases for haemodynamic instability; 2 cases for pericardial effusion without haemodynamic instability; 4 cases for urgent TAVR. The 30-days and 1-year all-cause mortality were 2.1% and 10.2%, respectively. Cardiac mortality at 30-days and 1-year follow-up were 0.6% and 4.1%, respectively. Intra-procedural and pre-discharge TT evaluation showed good agreement for PVL quantification (k agreement: 0.827, P = 0.005). CONCLUSION: TTE monitoring seems a reasonable imaging tool for TAVR intra-procedural monitoring without delay in diagnosis of complications and a reliable paravalvular leak assessment. However, TEE is undoubtedly essential in identifying the exact mechanism in most of the complications.

Transcatheter aortic valve implantation: current status and future perspectives.

In the 16 years since the first pioneering procedure, transcatheter aortic valve implantation (TAVI) has come of age and become a routine strategy for aortic valve replacement, increasingly performed under conscious sedation via transfemoral access. Simplification of the procedure, accumulation of clinical experience, and improvements in valve design and delivery systems have led to a dramatic reduction in complication rates. These advances have allowed transition to lower risk populations, and outcome data from the PARTNER 2A and SURTAVI trials have established a clear evidence base for use in intermediate risk patients. Ongoing studies with an expanding portfolio of devices seem destined to expand indications for TAVI towards lower risk, younger and asymptomatic populations. In this article, we outline recent advances, new devices and current guidelines informing the use of TAVI, and describe remaining uncertainties that need to be addressed.

Patient selection and percutaneous technique of unprotected left main revascularization.

Increasing evidence suggests that percutaneous coronary intervention with newer generation drug-eluting stents may be an acceptable alternative, or even preferred in selected cases to the surgical approach, in patients with left main disease. This review will discuss the anatomic factors, the clinical variables, and the procedural strategies to consider, including physiology assessment and imaging guidance, in order to optimize outcomes.

The last frontier: transcatheter devices for percutaneous or minimally invasive treatment of chronic heart failure.

Heart failure has a high prevalence in the general population. Morbidity and mortality of heart failure patients remain high, despite improvements in drug therapy, implantable cardioverter-defibrillators and cardiac resynchronisation therapy. New transcatheter implantable devices have been developed to improve the treatment of heart failure. There has been a rapid development of minimally invasive or transcatheter devices used in the treatment of heart failure associated with aortic and mitral valve disease and these devices are being incorporated into routine clinical practice at a fast rate. Several other new transcatheter structural heart interventions for chronic heart failure aimed at a variety of pathophysiologic approaches are currently being developed. In this review, we focus on devices used in the treatment of chronic heart failure by means of left ventricular remodelling, left atrial pressure reduction, tricuspid regurgitation reduction and neuromodulation. The clinical evaluations of these devices are early-stage evaluations of initial feasibility and safety studies and additional clinical evidence needs to be gathered in appropriately designed clinical trials.

The diabetic dilemma: which drug-eluting stent works best?

The relationship between diabetes mellitus and coronary artery disease is well established. The percentage of patients participating in clinical trials of percutaneous coronary intervention (PCI) who have diabetes is quickly rising. Diabetic patients have a worse prognosis than non-diabetics, with generally greater rates of death, myocardial infarction and need for target lesion and vessel revascularization. Stenting has improved the outcome of diabetic patients receiving PCI. Compared with bare-metal stents, the use of drug-eluting stents has resulted in a significant reduction in late lumen loss, binary restenosis, and clinically driven target vessel revascularization even in diabetic patients. Although surgical revascularization remains the recommended revascularization strategy for diabetics, particularly in case of multivessel coronary artery disease, recent progress in interventional devices and techniques have resulted in a changing paradigm for coronary artery revascularization. New stent designs, polymers and drugs are resulting in better outcomes overall, but more research is required to define their relative efficacy relative to other treatment options in this complex subgroup of patients.

Nitinol stents with polymer-free paclitaxel coating for stenosis of failing infrainguinal bypass grafts.

AIM: This study was designed to investigate the immediate and one-year outcomes of polymer-free paclitaxel coated drug-eluting stent (DES) implantation in a consecutive series of patients presenting with stenosis of infrainguinal bypass grafts. METHODS: Between January 2011 and January 2012, 11 patients with failing infrainguinal bypass grafts were treated in two institutions. Clinical status and Duplex scan parameters were recorded at baseline and over a follow-up period of one year. RESULTS: DES implantation was successfully performed in all patients. Ten patients received a single stent and one patient received two stents. At one year, one patient showed total bypass graft occlusion (9%). In all the remaining patients, Duplex scan examination documented patency of the treated grafts. CONCLUSION: DES implantation in failing infrainguinal bypass grafts can be safely performed and provides satisfactory clinical outcomes. The patency rate of 91% favourably compares with those obtained with other endovascular treatments such as plain balloon or cutting balloon angioplasty.

Which patients could benefit the most from bioresorbable vascular scaffold implant: from clinical trials to clinical practice.

Bioresorbable scaffold technology has evol-ved over the last few years with a number of devices either available or under clinical and preclinical investigation. The absence of a permanent metallic segment in the treated vessel wall has the potential of addressing some of the issues still encountered with metallic drug-eluting stents (DES) despite improvements in stent platform, polymer and drug elution. To date however, the use of bioresorbable vascular scaffolds (BVS) has largely been restricted to patients recruited into clinical trials with a relatively small number of "real-world" patients treated with these devices. Here we explore the issue of BVS use in "real-world" patients and try to identify, on the basis of our experience, the subset of patients that could benefit the most.

Bailout directional atherectomy for side branch salvage following subintimal recanalization of infragenicular arteries.

A 64-year old diabetic male presenting with critical limb ischemia was treated with percutaneous angioplasty for occlusion of the infragenicular popliteal artery and crural vessels. Directional atherectomy was uncommonly used in the false lumen created by following subintimal angioplasty of the infrapopliteal vessels for re-access into the true lumen. The positive clinical and angiographic results indicate that atherectomy can be considered a useful tool for rescue interventions to reopen large side branches unintentionally occluded during subintimal angioplasty.

Adjusted indirect comparison of new oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Vit-K antagonists are the therapy of choice to prevent thromboembolic events due to atrial fibrillation since many years. New oral anticoagulants (NOA) showed encouraging results vs. warfarin but there are no data directly comparing different NOA. We performed an adjusted indirect meta-analysis. METHODS: Randomized controlled trials (RCTs) were searched. Efficacy end points were the cumulative rate of thomboembolic stroke (TES) and systemic embolism (SE). Main safety end point was the rate of hemorrhagic stroke (HS). RESULTS: Three RCTs (50578 patients) were included. Overall, NOA were comparable to warfarin according to the cumulative risk of TES and SE, as well as for TES alone. NOA were associated with a reduced rate of SE [OR 0.64 (0.44, 0.94], P=0.02]. Compared to warfarin, NOA were associated with a significantly reduced risk of HS [OR 0.43 (0.34, 0.55), P<0.001, NNT to avoid a HS 153] and all cause death [OR 0.90 [0.84, 0.96], P=0.03, NNT to save one fatality 43]. Head to head comparison showed that in terms of cumulative rate of TES/SE, as well as of TES, none of the NOA was significantly superior to the others (all Ps>0.05). Rivaroxaban showed superiority in the prevention of SE. Dabigatran 150 mg/twice daily was associated with the largest reduction in the risk of HS vs. warfarin and vs. other NOA. Overall mortality was quite comparable across NOA. CONCLUSION: Overall superiority of NOA over warfarin is largely influenced by the reduction of HS. Dabigatran 150 mg/twice daily seems to have the best risk/benefit profile.

Defining a new standard for IVUS optimized drug eluting stent implantation: the PRAVIO study.

OBJECTIVES: Preliminary Investigation to the Angiographic Versus IVUS Optimization Trial is a single center prospective observational intravascular ultrasound (IVUS) guided stent implantation study assessing new criteria for optimal drug eluting stent (DES) deployment. BACKGROUND: IVUS assessment of DES often reveals underexpansion and malapposition. Optimal stent deployment is currently poorly defined and previous criteria may not be suitable in long and complex lesions. METHODS: Optimization was defined as achieving >/or 70% of the cross-sectional area (CSA) of the postdilation balloon. This criterion was applied in 113 complex lesions. The size of this balloon was calculated according to vessel media-to-media diameters at various sites inside the stented segment. The IVUS guided treated lesions were matched according to diabetes, vessel type, reference vessel diameter, minimum lumen diameter (MLD), and lesion length with a group of angiographic treated lesions to compare final MLD achieved. RESULTS: Mean minimum stent CSA according to the postdilation balloon utilized was 4.62 mm(2), 6.26 mm(2), 7.87 mm(2), and 9.87 mm(2) for 2.5 mm, 3.0 mm, 3.5 mm, and 4 mm balloons, respectively. Final MLD (mm) was significantly larger in the IVUS compared to the angiographic-guided group (3.09 +/- 0.50 vs. 2.67 +/- 0.54; P < 0.0001). There were no procedural complications related to IVUS use. CONCLUSIONS: We propose new IVUS criteria based on vessel remodeling that results in an increment in the final MLD, compared to angiographic guidance, which is much larger than any previously published study. This criterion seems to be safely achievable. A proposed randomized study (angiographic vs. IVUS optimization trial) has been launched to test these concepts.

Bifurcation stenting: current strategies and new devices.

Based on the results of numerous randomised trials, the provisional approach of implanting one stent on the main branch has become the default approach to most bifurcation lesions. However, bifurcation intervention still remains technically challenging. Dedicated bifurcation stents have been designed to specifically treat coronary bifurcations with the aim of dealing with some of the shortcomings of the conventional percutaneous approach to bifurcation intervention. Most of the devices are aimed at facilitating the provisional approach. They are an exciting and innovative technology that may further simplify the management and current approach to bifurcation treatment. Currently, 11 devices are available that have either completed or are currently undergoing First-In-Man trials. The development of more drug-eluting platforms and larger studies with control groups demonstrating their clinical applicability, efficacy and safety are required before they are widely incorporated into daily practice.

Bioabsorbable and biocompatible stents. Is a new revolution coming?

With the introduction of drug-eluting stents (DES) the problem of restenosis after percutaneous stent implantation was partially resolved. In the first generation of DES a stainless steel platform was coated with a durable polymer eluting and controlling the release of an active restenotic drug. The impairment of re-endothelization after DES implantation, one of the causes of late stent thrombosis, was to some extent attributed to the properties of the durable polymer and/or drug that it eluted. The introduction of biodegradable platforms and biocompatible polymers may potentially address this issue. Modern technologies are being applied to improve the characteristics of biodegradable stents and find new active pharmacological agents or combinations of standard antirestenotic and antithrombotic drugs that can be eluted from the stents, in order to improve their safety profile and clinical utility.