Characteristics and Outcomes of Cardiac Rehabilitation Patients With and Without Cancer: Insights From Western Sydney.

AIM: Increased cardiovascular events are common in cancer survivors and contribute to an emerging cardio-oncology patient group requiring secondary prevention strategies including cardiac rehabilitation (CR). This study aimed to compare characteristics and outcomes for patients participating in CR with and without an existing cancer diagnosis. METHOD: Observational cohort study including consecutive patients enrolled in a single-centre outpatient CR program in Western Sydney between 2018-2022. Clinical history, demographics and CR outcome data were collected as part of standard care at program enrolment and completion. Patients with and without a cancer diagnosis were compared at enrolment and outcomes were analysed in both groups. RESULTS: A total of 1,792 patients enrolled in CR, 191 (11%) had a documented history of cancer; prostate (18%), skin (12%), colon (9%) and breast (8%) malignancies were most prevalent. The most common treatments were surgical resection (80%) and chemotherapy or radiotherapy (37%). Cardio-oncology patients were older (68.8±10.6 vs 59.8±13.7yrs, p<0.001), more likely female (33% vs 21%, p<0.001), born in Australia (46% vs 35%, p=0.004), non-partnered (34% vs 25%, p=0.002) and had a prior history of hypertension (65% vs 56%, p=0.010) or stroke (8% vs 5%, p=0.045). After adjusting for age and sex, the overall cohort improved their mean peak exercise capacity and waist circumference after CR, however there were no differences between groups. There were also no between-group differences for adherence and completion of CR program or any other cardiovascular risk factors. Sub-analyses revealed a clinically meaningful improvement in waist circumference for cancer patients with a history of radiation therapy and a blunted peak exercise capacity adaptation for those with a history of chemotherapy treatment. CONCLUSIONS: Despite differences in demographic and clinical characteristics of CR patients with and without cancer, all patients showed significant and clinically relevant improvements in peak exercise capacity and waist circumference after CR. Results also highlighted potential associations between specific cancer treatments and changes in fitness outcomes, which warrants further evaluation.

A National Survey of Patient Data Capture, Management, Reporting Practice in Australian Cardiac Rehabilitation Programs.

BACKGROUND: Lack of service data for cardiac rehabilitation limits understanding of program delivery, benchmarking and quality improvement. This study aimed to describe current practices, management, utilisation and engagement with quality indicators in Australian programs. METHOD: Cardiac rehabilitation programs (n=396) were identified from national directories and networks. Program coordinators were surveyed on service data capture, management systems and adoption of published national quality indicators. Text responses were coded and classified. Logistic regression determined independent associates of the use of data for quality improvement. RESULTS: A total of 319 (81%) coordinators completed the survey. Annual patient enrolments/programs were >200 (31.0%), 51-200 (46%) and ≤50 (23%). Most (79%) programs used an electronic system, alongside paper (63%) and/or another electronic system (19%), with 21% completely paper. While 84% knew of the national quality indicators, only 52% used them. Supplementary to patient care, data were used for reports to managers (57%) and funders (41%), to improve quality (56%), support funding (43%) and research (31%). Using data for quality improvement was more likely when enrolments where >200 (Odds ratio [OR] 3.83, 95% Confidence Interval [CI] 1.76-8.34) and less likely in Victoria (OR 0.24 95%, CI 0.08-0.77), New South Wales (OR 0.25 95%, CI 0.08-0.76) and Western Australia (OR 0.16 95%, CI 0.05-0.57). CONCLUSIONS: The collection of service data for cardiac rehabilitation patient data and its justification is diverse, limiting our capacity to benchmark and drive clinical practice. The findings strengthen the case for a national low-burden approach to data capture for quality care.

An interdisciplinary multimodal integrative healthcare program for depressive and anxiety disorders.

Objective: Although multimodal interventions are recommended in patients with severe depressive and/or anxiety disorders, available evidence is scarce. Therefore, the current study evaluates the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, for patients with (comorbid) depressive and/or anxiety disorders. Methods: Participants were 3,900 patients diagnosed with a depressive and/or anxiety disorder. The primary outcome was Health-Related Quality of Life (HRQoL) measured with the Research and Development-36 (RAND-36). Secondary outcomes included: (1) current psychological and physical symptoms measured with the Brief Symptom Inventory (BSI) and (2) symptoms of depression, anxiety, and stress measured with the Depression Anxiety Stress Scale (DASS). The healthcare program consisted of two active treatment phases: main 20-week program and a subsequent continuation-phase intervention (i.e., 12-month relapse prevention program). Mixed linear models were used to examine the effects of the healthcare program on primary/secondary outcomes over four time points: before start 20-week program (T0), halfway 20-week program (T1), end of 20-week program (T2) and end of 12-month relapse prevention program (T3). Results: Results showed significant improvements from T0 to T2 for the primary variable (i.e., RAND-36) and secondary variables (i.e., BSI/DASS). During the 12-month relapse prevention program, further significant improvements were mainly observed for secondary variables (i.e., BSI/DASS) and to a lesser extent for the primary variable (i.e., RAND-36). At the end of the relapse prevention program (i.e., T3), 63% of patients achieved remission of depressive symptoms (i.e., DASS depression score ≤ 9) and 67% of patients achieved remission of anxiety symptoms (i.e., DASS anxiety score ≤ 7). Conclusion: An interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, seems effective for patients suffering from depressive and/or anxiety disorders with regard to HRQoL and symptoms of psychopathology. As reimbursement and funding for interdisciplinary multimodal interventions in this patient group has been under pressure in recent years, this study could add important evidence by reporting on routinely collected outcome data from a large patient group. Future studies should further investigate the long-term stability of treatment outcomes after interdisciplinary multimodal interventions for patients suffering from depressive and/or anxiety disorders.

An interdisciplinary multimodal integrative healthcare program for somatic symptom disorder, with predominant (spinal) pain.

OBJECTIVE: Although multimodal interventions are generally recommended in patients with long-term somatic symptom disorders (SSD), available evidence is limited. The current study evaluates the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program for patients with SSD and predominant (spinal) pain. METHOD: The healthcare program consisted of two active treatment phases: main 20-week program and a 12-month relapse prevention program. Participants were 4453 patients diagnosed with SSD. The primary outcome was health-related quality of life (HRQoL) assessed using the RAND-36 (i.e., mental/physical component summary) and secondary outcomes included physical and psychological symptoms assessed using the Brief Symptom Inventory (BSI) and RAND-36 subscales. Mixed linear models were used to examine the effects of the multimodal healthcare program on primary/secondary outcomes over four time points: before start 20-week program (T0), halfway 20-week program (T1), end of 20-week program (T2) and end of relapse prevention program (T3). RESULTS: Significant improvements were found from T0 to T2 for all primary variables (i.e., mental/physical component summary) and secondary variables (i.e., BSI/RAND-36 subscales), which were maintained until the end of the relapse prevention program (T3). CONCLUSION: An interdisciplinary multimodal integrative treatment for SSD is effective for improving HRQoL and reducing physical and psychological symptoms.

The Effect of Self-Paced Exercise Intensity and Cardiorespiratory Fitness on Frontal Grey Matter Volume in Cognitively Normal Older Adults: A Randomised Controlled Trial.

OBJECTIVE: Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults. METHODS: Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention. RESULTS: The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (ß = 0.29, p = 0.036, r = 0.27), right supplementary motor area (ß = 0.30, p = 0.031, r = 0.29), and both right (ß = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (ß = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups. CONCLUSIONS: At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.

Primary Outcome Evaluation of a Next-Generation Left Atrial Appendage Closure Device: Results From the PINNACLE FLX Trial.

BACKGROUND: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. METHODS: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. RESULTS: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA2DS2-VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% (P<0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% (P<0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. CONCLUSIONS: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02702271.

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score.

BACKGROUND: Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX™ (ODX) recurrence scores has been observed to explain this health disparity. Black women are also disproportionately affected by insulin resistance. We evaluated whether insulin resistance is associated with a higher ODX recurrence score and whether there is a difference between White and Black women to explain disparate clinical outcomes. METHODS: A subgroup analysis of patients in a multi-institutional cross-sectional study evaluating differences in insulin resistance between White and Black women was performed. Women diagnosed with a new hormone receptor-positive, HER2/neu-negative breast cancer with an ODX recurrence score were identified. Fasting blood glucose and insulin measurements were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) score, a method for assessing insulin resistance, and compared against ODX scores. RESULTS: Overall, 412 women (358 White women, 54 Black women) were identified. Compared with White women, Black women had a higher body mass index (30 vs. 26 kg/m2, p < 0.0001), higher HOMA-IR score (2.4 vs. 1.4, p = 0.004), and more high-grade tumors (30% vs. 16%, p = 0.01). There was a direct positive association with an increasing ODX score and HOMA-IR (p = 0.014). On subset analysis, this relationship was seen in White women (p = 0.005), but not in Black women (p = 0.55). CONCLUSION: In women with newly diagnosed breast cancer, increasing insulin resistance is associated with a higher recurrence score; however, this association was not present in Black women. This lack of association may be due to the small number of Black women in the cohort, or possibly a reflection of a different biological disease process of the patient's tumor.

High-intensity exercise and cognitive function in cognitively normal older adults: a pilot randomised clinical trial.

BACKGROUND: Physical inactivity has been consistently linked to increased risk of cognitive decline; however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements; however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. METHODS: This multi-arm pilot randomised clinical trial investigated the effects of 6 months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12 months post-intervention. Ninety-nine cognitively normal men and women (aged 60-80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e. high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. RESULTS: There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness, whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. CONCLUSIONS: We did not observe a direct effect of exercise on cognition. Future work in this field should be appropriately designed and powered to examine factors that may contribute to individual variability in response to intervention. TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered on 3 May 2017-retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780.

A Randomized Controlled Trial of High-Intensity Exercise and Executive Functioning in Cognitively Normal Older Adults.

BACKGROUND: There is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function. METHODS: Ninety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO2peak. RESULTS: First, the exercise intervention was found to increase cardiorespiratory fitness (VO2peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (ß = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (ß = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants. CONCLUSION: At the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity.

Single-leg cycling increases limb-specific blood flow without concurrent increases in normalised power output when compared with double-leg cycling in healthy middle-aged adults.

This study examined the acute performance, cardiovascular and local muscular responses to perceived exertion-based high-intensity interval exercise using either double- or single-leg cycling. Fifteen healthy middle-aged adults completed, on separate occasions, ten 30-s double-leg intervals interspersed with 60 s passive recovery and twenty (ten with each leg) 30-s single-leg intervals interspersed with 60 s passive recovery. Impedance cardiography, blood pressure, muscle oxygenation and total haemoglobin content (near-infrared spectroscopy), oxygen consumption and power output were measured throughout each session. Normalised to the lean mass used during each trial, single-leg cycling resulted in lower power output (single-leg: 8.92 ± 1.74 W kg-1 and double-leg: 10.41 ± 3.22 W kg-1; p < 0.05) but greater oxygen consumption (single-leg: 103 ± 11 mL kg-1 min-1 and double-leg: 84 ± 21 mL kg-1 min-1; p < 0.01) and cardiac output (single-leg: 1407 ± 334 mL kg-1 min-1 and double-leg: 850 ± 222 mL kg-1 min-1; p < 0.01), compared with double-leg cycling. Mean arterial pressure (double-leg: 108 ± 11 mmHg and single-leg: 102 ± 10 mmHg), change in total haemoglobin content (double-leg: 8.76 ± 10.65 µM cm s-1 and single-leg: 13.42 ± 4.10 µM cm s-1) and change in tissue oxygenation index (double-leg: -4.51 ± 3.56% and single-leg: -3.97 ± 3.91%) were not different between double-leg and single-leg cycling. When compared to double-leg cycling, single-leg cycling elicited a higher cardiac output relative to the lean mass, but this did not result in greater power output. The dissociation between blood availability and power output is consistent with an ageing model characterised by a decrease in local oxygen delivery and distribution capability.

Combining left atrial appendage closure and catheter ablation for atrial fibrillation: 2-year outcomes from a multinational registry.

AIMS: Clinical practice guidelines do not recommend discontinuation of long-term oral anticoagulation in patients with a high stroke risk after catheter ablation for atrial fibrillation (AF). Left atrial appendage closure (LAAC) with Watchman has emerged as an alternative to long-term anticoagulation for patients accepting of the procedural risks. We report on the long-term outcomes of combining catheter ablation procedures for AF and LAAC from multicentre registries. METHODS AND RESULTS: Data were pooled from two prospective, real-world Watchman LAAC registries running in parallel in Europe/Middle-East/Russia (EWOLUTION) and Asia/Australia (WASP) between 2013 and 2015. Of the 1140 patients, 142 subjects at 11 centres underwent a concomitant AF ablation and LAAC procedure. The mean CHA2DS2-VASc score was 3.4 ± 1.4 and HAS-BLED score 1.5 ± 0.9. Successful LAAC was achieved in 99.3% of patients. The 30-day device and/or procedure-related serious adverse event rate was 2.1%. After a mean follow-up time of 726 ± 91 days, 92% of patients remained off oral anticoagulation. The rates of the composite endpoint of ischaemic stroke/transient ischaemic attack/systemic thromboembolism were 1.09 per 100 patient-years (100-PY); and for non-procedural major bleeding were 1.09 per 100-PY. These represent relative reductions of 84% and 70% vs. expected rates per risk scores. CONCLUSION: The long-term outcomes from these international, multicentre registries show efficacy for all-cause stroke prevention and a significant reduction in late bleeding events in a population of high stroke risk post-ablation patients who have been withdrawn from oral anticoagulation.

Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries.

BACKGROUND: Long-term data on the safety and efficacy of left atrial appendage closure (LAAC) for stroke prevention in patients with nonvalvular atrial fibrillation remain limited. OBJECTIVES: The purpose of this study was to evaluate 4.5- to 5-year data in 2 U.S. Food and Drug Association LAAC mandated registries (CAP [Continued Access to PROTECT-AF] and CAP2 [Continued Access to PREVAIL]) for safety and efficacy. METHODS: Two registries of patients implanted with LAAC devices provide the largest source of follow-up data. Both accompanied their respective randomized clinical trials, PROTECT-AF (Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device In Patients with Atrial Fibrillation versus Long Term Warfarin Therapy), which used the same endpoints (primary efficacy of composite of stroke, systemic embolism, cardiovascular/unexplained death, and safety). RESULTS: CAP included 566 patients with an average follow-up of 50.1 months (2,293 patient-years), and CAP2 included 578 patients with an average follow-up of 50.3 months (2,227 patient-years). CAP2 patients were significantly older and had higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) scores (4.51 vs. 3.88; p < 0.001). Procedural success was similar in both (94%). The primary composite endpoint occurred at a rate of 3.05 per 100 patient-years in CAP and 4.80 per 100 patient-years in CAP2; events contributing to this endpoint were most commonly cardiovascular/unexplained death (1.69 per 100 patient-years for CAP and 2.92 per 100 patient-years for CAP2). Hemorrhagic stroke was significantly less than ischemic stroke (0.17 per 100 patient-years in CAP and 0.09 per 100 patient-years in CAP2), and total stroke rates were significantly less than predicted by CHA2DS2-VASc score (78% reduction with CAP, 69% reduction with CAP2). CONCLUSIONS: These registries, which contain the longest and largest follow-up data of patients with the Watchman device, support LAAC as a safe and effective therapy for long-term anticoagulation in patients with nonvalvular atrial fibrillation, and document the lowest rate of hemorrhagic stroke identified in this population.

Resistance training enhances delayed memory in healthy middle-aged and older adults: A randomised controlled trial.

OBJECTIVES: High-intensity exercise is a potential therapeutic tool to postpone or prevent the onset of cognitive decline. However, there is a lack of sufficient evidence regarding the longitudinal effects of structured resistance training on cognitive function in healthy adults. The purpose of this study was to investigate the effect of two ecologically valid, intense 12-week resistance training programs on cognitive function in late middle-aged adults. DESIGN: Single-site parallel randomised controlled trial at the Department of Exercise Science strength and conditioning laboratory. Groups allocated by minimisation randomisation. METHODS: Forty-five healthy adults (age range=41-69 years) were enrolled and randomised into (A) high-load, long rest resistance training (n=14), or (B) moderate-load, short rest resistance training (n=15) twice per week for 12 weeks, or a non-exercising control (n=16). Follow-up within seven days. Data were collected September 2016-December 2017. Cognitive function assessed using the CogState computerised battery. Assessors were blinded to participant group allocation. Secondary outcomes were maximal muscle strength and body composition. RESULTS: Forty-four participants were analysed in 2018. Delayed verbal memory performance was improved (p=0.02) in resistance training groups (g=0.67-0.79) when compared to the control group, with no differences between training groups. Likewise, increases in maximal muscle strength were observed (p<0.01) in resistance training groups when compared to the control group, with no differences between training groups. No differences in body composition were observed. There were no adverse events or side-effects of the intervention. CONCLUSIONS: 12 weeks of intense resistance training improves delayed verbal memory irrespective of training design (i.e., high-load vs. moderate-load). TRIAL REGISTRATION: This study is registered at www.anzctr.org.au ACTRN12616000690459.

High-Intensity Single-Leg Cycling Improves Cardiovascular Disease Risk Factor Profile.

INTRODUCTION: Regular exercise can reduce the risk of developing cardiovascular disease through risk factor modification, with high-intensity exercise and more recently small muscle mass training providing alternatives to moderate-intensity exercise. METHODS: This study randomly assigned 53 healthy middle-age adults (age, 62 ± 6 yr) to complete 24 sessions (8 wk; 3 d·wk) of exercise training, using either high-intensity double-leg cycling (n = 17; HITDL), high-intensity single-leg cycling (n = 18; HITSL), or moderate-intensity double-leg cycling (n = 18; MCTDL). Biomarkers of cardiovascular risk (total cholesterol, triglycerides, HDL-c, LDL-c, apo-B48, and glucose), anthropometry measures (body mass, body mass index, waist circumference, and waist-to-hip ratio), resting blood pressure, and aerobic capacity were assessed pre- and postintervention. RESULTS: Total work completed was greater (P < 0.01) in MCTDL (5938 ± 1462 kJ) compared with the HITDL (3462 ± 1063 kJ) and HITSL (4423 ± 1875 kJ). Pre- to posttraining differences were observed for waist-to-hip ratio (0.84 ± 0.09 vs 0.83 ± 0.09; P < 0.01), resting systolic blood pressure (129 ± 11 vs 124 ± 12 mm Hg; P < 0.01), total cholesterol (5.87 ± 1.17 vs 5.55 ± 0.98 mmol·L; P < 0.01), and LDL-c (3.70 ± 1.04 vs 3.44 ± 0.84 mmol·L; P < 0.01), with no differences between conditions. In addition, aerobic capacity increased after training (22.3 ± 6.4 vs 24.9 ± 7.6 mL·kg·min; P < 0.01), with no differences between conditions. CONCLUSION: These findings suggest that all three modes of exercise can be prescribed to achieve cardiovascular risk reduction in an aging population.

Left atrial appendage closure with WATCHMAN in Asian patients: 2 year outcomes from the WASP registry.

BACKGROUND: Left atrial appendage closure is a non-pharmacological alternative for stroke prevention in high-risk non-valvular atrial fibrillation patients, but has not been widely studied in Asian patients. The prospective WASP registry assessed real-world outcomes for patients undergoing WATCHMAN implant in the Asia-Pacific region. METHODS: Data were collected from consecutive patients across 9 centres. Major endpoints included procedural success, safety and long-term outcomes including occurrence of bleeding, stroke/transient ischaemic attack/systemic embolism and all-cause mortality. RESULTS: Subjects (n = 201) had a mean age of 70.8 ±â€¯9.4 years, high stroke risk (CHA2DS2-VASc: 3.9 ±â€¯1.7), elevated bleeding risk (HAS-BLED: 2.1 ±â€¯1.2) with 53% patients from Asian countries. Successful implantation occurred in 98.5% of patients; 7-day device/procedure-related SAE rate was 3.0%. After 2 years of follow-up, the rates of ischaemic stroke/TIA/SE and major bleeding were 1.9 and 2.2 per 100-PY, respectively, representing relative reductions of 77% and 49% versus expected rates per risk scores. The relative risk reductions versus expected rates were more pronounced in Asians vs. Non-Asians (89% vs 62%; 77% vs 14%). Other significant findings included larger mean LAA ostium diameter for Asians vs. Non-Asians (23.4 ±â€¯4.1 mm vs. 21.2 ±â€¯3.2 mm, p < 0.001) and hence requirement for larger median device size (27 mm for Asians, 24 mm for non-Asians [p < 0.0001]). CONCLUSION: Real-world experience of left atrial appendage closure with WATCHMAN has demonstrated low peri-procedural risk, and long-term efficacy for stroke and bleeding prevention in a primarily Asian cohort.

Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: In patients with atrial fibrillation, left atrial appendage closure with the Watchman device prevents thromboembolism from the left atrial appendage; however, thrombus may form on the left atrial face of the device, and then potentially embolize. Herein, we studied the incidence, predictors, and clinical outcome of device-related thrombus (DRT) using a large series of clinical trial cohorts of patients undergoing Watchman implantation. METHODS: We studied the device arms of 4 prospective Food and Drug Administration trials: PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) (n=463); PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) (n=269); CAP (Continued Access to PROTECT AF registry) (n=566); and CAP2 (Continued Access to PREVAIL registry) (n=578). Surveillance transesophageal echocardiographs were performed at 45 days and 12 months in all patients, and also at 6 months in the randomized control trials. We assessed both the incidence of DRT during these transesophageal echocardiographs (and other unscheduled transesophageal echocardiographs), and clinical outcomes of postprocedure stroke or systemic embolism (SSE) and adjusted for CHA2DS2-VASC and HAS-BLED scores. RESULTS: Of 1739 patients who received an implant (7159 patient-years follow-up; CHA2DS2-VASc=4.0), DRT was seen in 65 patients (3.74%). The rates of SSE with and without DRT were 7.46 and 1.78 per 100 patient-years (adjusted rate ratio, 3.55; 95% confidence interval [CI], 2.18-5.79; P<0.001), and ischemic SSE rates were 6.28 and 1.65 per 100 patient-years (adjusted rate ratio, 3.22; 95% CI, 1.90-5.45, P<0.001). On multivariable modeling analysis, the predictors of DRT were as follows: history of transient ischemic attack or stroke (odds ratio [OR], 2.31; 95% CI, 1.26-4.25; P=0.007), permanent atrial fibrillation (OR, 2.24; 95% CI, 1.19-4.20; P=0.012); vascular disease (OR, 2.06; 95% CI, 1.08-3.91; P=0.028); left atrial appendage diameter (OR, 1.06 per mm increase; 95% CI, 1.01-1.12; P=0.019); left ventricular ejection fraction (OR, 0.96 per 1% increase; 95% CI, 0.94-0.99; P=0.009). DRT and SSE both occurred in 17 of 65 patients (26.2%). Of the 19 SSE events in these patients with DRT, 9 of 19 (47.4%) and 12 of 19 (63.2%) occurred within 1 and 6 months of DRT detection. Conversely, after left atrial appendage closure, most SSEs (123/142, 86.62%) occurred in patients without DRT. CONCLUSIONS: After left atrial appendage closure with Watchman, DRT (≈3.7%) is not frequent but, when present, is associated with a higher rate of stroke and systemic embolism.

Active and Inactive Leg Hemodynamics during Sequential Single-Leg Interval Cycling.

INTRODUCTION: Leg order during sequential single-leg cycling (i.e., exercising both legs independently within a single session) may affect local muscular responses potentially influencing adaptations. This study examined the cardiovascular and skeletal muscle hemodynamic responses during double-leg and sequential single-leg cycling. METHODS: Ten young healthy adults (28 ± 6 yr) completed six 1-min double-leg intervals interspersed with 1 min of passive recovery and, on a separate occasion, 12 (six with one leg followed by six with the other leg) 1-min single-leg intervals interspersed with 1 min of passive recovery. Oxygen consumption, heart rate, blood pressure, muscle oxygenation, muscle blood volume, and power output were measured throughout each session. RESULTS: Oxygen consumption, heart rate, and power output were not different between sets of single-leg intervals, but the average of both sets was lower than the double-leg intervals. Mean arterial pressure was higher during double-leg compared with sequential single-leg intervals (115 ± 9 vs 104 ± 9 mm Hg, P < 0.05) and higher during the initial compared with second set of single-leg intervals (108 ± 10 vs 101 ± 10 mm Hg, P < 0.05). The increase in muscle blood volume from baseline was similar between the active single leg and the double leg (267 ± 150 vs 214 ± 169 µM·cm, P = 0.26). The pattern of change in muscle blood volume from the initial to second set of intervals was significantly different (P < 0.05) when the leg was active in the initial (-52.3% ± 111.6%) compared with second set (65.1% ± 152.9%). CONCLUSIONS: These data indicate that the order in which each leg performs sequential single-leg cycling influences the local hemodynamic responses, with the inactive muscle influencing the stimulus experienced by the contralateral leg.

The effects of cryopreserved red blood cell transfusion on tissue oxygenation in obese trauma patients.

BACKGROUND: Low tissue oxygenation (StO2) is associated with poor outcomes in obese trauma patients. A novel treatment could be the transfusion of cryopreserved packed red blood cells (CPRBCs), which the in vitro biochemical profile favors red blood cell (RBC) function. We hypothesized that CPRBC transfusion improves StO2 in obese trauma patients. METHODS: Two hundred forty-three trauma patients at five Level I trauma centers who required RBC transfusion were randomized to receive one to two units of liquid packed RBCs (LPRBCs) or CPRBCs. Demographics, injury severity, StO2, outcomes, and biomarkers of RBC function were compared in nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) patients. StO2 was also compared between obese patients with BMI of 30 to 34.9 and BMI ≥ 35. StO2 was normalized and expressed as % change after RBC transfusion. A p value less than 0.05 indicated significance. RESULTS: Patients with BMI less than 30 (n = 141) and BMI of 30 or greater (n = 102) had similar Injury Severity Score, Glasgow Coma Scale, and baseline StO2. Plasma levels of free hemoglobin, an index of RBC lysis, were lower in obese patients after CPRBC (125 [72-259] µg/mL) versus LPRBC transfusion (230 [178-388] µg/mL; p < 0.05). StO2 was similar in nonobese patients regardless of transfusion type, but improved in obese patients who received CPRBCs (104 ± 1%) versus LPRPCs (99 ± 1%, p < 0.05; 8 hours after transfusion). Subanalysis showed improved StO2 after CPRBC transfusion was specific to BMI of 35 or greater, starting 5 hours after transfusion (p < 0.05 vs. LPRBCs). CPRBCs did not improve clinical outcomes in either group. CONCLUSION: CPRBC transfusion is associated with increased StO2 and lower free hemoglobin levels in obese trauma patients, but did not improve clinical outcomes. Future studies are needed to determine if CPRBC transfusion in obese patients attenuates hemolysis to improve StO2. LEVEL OF EVIDENCE: Therapeutic, level IV.

Combining Watchman left atrial appendage closure and catheter ablation for atrial fibrillation: multicentre registry results of feasibility and safety during implant and 30 days follow-up.

Aims: Long-term results from catheter ablation therapy for atrial fibrillation (AF) remain uncertain and clinical practice guidelines recommend continuation of long-term oral anticoagulation in patients with a high stroke risk. Left atrial appendage closure (LAAC) with Watchman has emerged as an alternative to long-term anticoagulation for patients accepting of the procedural risks. We report on the initial results of combining catheter ablation procedures for AF and LAAC in a multicentre registry. Methods and results: Data were pooled from two prospective, real-world Watchman LAAC registries running in parallel in Europe/Middle-East/Russia (EWOLUTION) and Asia/Australia (WASP) between 2013 and 2015. Of the 1140 patients, 139 subjects at 10 centres underwent a concomitant AF ablation and LAAC procedure. The mean CHA2DS2-VASc score was 3.4 ± 1.4 and HAS-BLED score 1.5 ± 0.9. Successful Watchman implantation was achieved in 100% of patients. The overall 30-day serious adverse event (SAE) rate was 8.7%, with the device and/or procedure-related SAE rate of 1.4%. One pericardial effusion required percutaneous drainage, but there were no strokes, device embolization, or deaths at 30 days. The 30-day bleeding SAE rate was 2.9% with 55% of patients prescribed NOAC and 38% taking warfarin post-procedure. Conclusion: The outcomes from these international, multicentre registries support the feasibility and safety of performing combined procedures of ablation and Watchman LAAC for patients with non-valvular AF and high stroke risk. Further data are needed on long-term outcomes for the hybrid technique on all-cause stroke and mortality.