Vascular function in continuous-flow left ventricular assist device recipients: effect of a single pulsatility treatment session.

Vascular function is further attenuated in patients with chronic heart failure implanted with a continuous-flow left ventricular assist device (LVAD), likely due to decreased arterial pulsatility, and this may contribute to LVAD-associated cardiovascular complications. However, the impact of increasing pulsatility on vascular function in this population is unknown. Therefore, 15 LVAD recipients and 15 well-matched controls underwent a 45-min, unilateral, arm pulsatility treatment, evoked by intermittent cuff inflation/deflation (2-s duty cycle), distal to the elbow. Vascular function was assessed by percent brachial artery flow-mediated dilation (%FMD) and reactive hyperemia (RH) (Doppler ultrasound). Pretreatment, %FMD (LVAD: 4.0 ± 1.7; controls: 4.2 ± 1.4%) and RH (LVAD: 340 ± 101; controls: 308 ± 94 mL) were not different between LVAD recipients and controls; however, %FMD/shear rate was attenuated (LVAD: 0.10 ± 0.04; controls: 0.17 ± 0.06%/s-1, P < 0.05). The LVAD recipients exhibited a significantly attenuated pulsatility index (PI) compared with controls prior to treatment (LVAD: 2 ± 2; controls: 15 ± 7 AU, P < 0.05); however, during the treatment, PI was no longer different (LVAD: 37 ± 38; controls: 36 ± 14 AU). Although time to peak dilation and RH were not altered by the pulsatility treatment, %FMD (LVAD: 7.0 ± 1.8; controls: 7.4 ± 2.6%) and %FMD/shear rate (LVAD: 0.19 ± 0.07; controls: 0.33 ± 0.15%/s-1) increased significantly in both groups, with, importantly, %FMD/shear rate in the LVAD recipients being restored to that of the controls pretreatment. This study documents that a localized pulsatility treatment in LVAD recipients and controls can recover local vascular function, an important precursor to the development of approaches to increase systemic pulsatility and reduce systemic vascular complications in LVAD recipients.

Plasma nitrite as an indicator of cerebral ischemia during extracranial/intracranial bypass surgery in moyamoya patients.

BACKGROUND AND PURPOSE: Nitric oxide (NO) plays a key role in ischemia and shows potential as a biomarker for ischemia. We measured mixed venous nitrite (NO2-) as a proxy for NO, during controlled cerebral ischemia in patients with moyamoya disease (MMD) during direct extracranial/intracranial (EC/IC) bypass surgery with temporary occlusion of the M4 branch of the middle cerebral artery (MCA) to permit anastomosis with the superficial temporal artery (STA). This small, focal ischemic event is not reliably detected using cerebral oximetry, somatosensory evoked potentials (SSEPs) or electroencephalography (EEG). METHODS: We enrolled nine adult MMD patients (n=8 female, n=1 male) undergoing direct EC/IC bypass surgery. Nitrite was measured at least one hour prior to MCA occlusion, and before, during and after anastomosis. Cortical function was monitored using either multi-lead EEG and SSEPs, or frontal EEG activity. RESULTS: Mixed venous NO2- was significantly elevated (p<0.05) within 12 min following arterial occlusion vs. baseline. An M4 branch of the MCA was cross clamped for a median duration of 18 (IQR = 5) minutes during anastomosis. One patient with elevated NO2- showed a transient neurologic deficit that resolved 3 days post-operatively. CONCLUSIONS: Mixed venous NO2- was significantly elevated shortly following cerebral artery occlusion vs. baseline in a majority of the study subjects, suggesting that NO2- is a potential biomarker for ischemia. Since all patients received identical burst suppression anesthesia and vasopressors, the fact that NO2- was not elevated during cross-clamp in all patients supports the conclusion that the NO2- elevation is likely due to ischemia.

Clinical Implications and Management Strategies for Left Atrial Appendage Leaks.

Left atrial appendage (LAA) is the dominant source of systemic thromboembolic (TE) events in patients with nonvalvular atrial fibrillation (AF). In patients with significant bleeding risk, various LAA exclusion strategies have been developed as an alternative to pharmacologic TE prophylaxis. Nevertheless, in a relatively small percentage of patients, incomplete LAA closure can be documented, either at the time of procedure or during follow-up. This persistent patency can potentially jeopardize an effective stroke prophylaxis. Hereby, we report an update on the current clinical implications of LAA leaks and how to manage them.

Epicardial versus Endocardial Closure: Is One Better than the Other?

Left atrial appendage occlusion is an evolving technology with demonstrable benefits of stroke prophylaxis in patients with atrial fibrillation unsuitable for anticoagulation. This has resulted in the development of a plethora of transcatheter devices to achieve epicardial exclusion and endocardial occlusion. In this review, the authors summarize the differences in technique, target patient population, outcomes, and complication profiles of endocardial and epicardial techniques.

Effect of Remote Ischemic Preconditioning on Patients Undergoing Elective Major Vascular Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Whether remote ischemic preconditioning (RIPC), through several cycles of ischemia-reperfusion, can generate endogenous protective substances to protect patients undergoing elective major vascular surgery remains unclear. The results derived from many randomized controlled trials (RCTs) have been discrepant. METHODS: PubMed (1966 to May 2018) and EMBASE (1966 to May 2018) databases were searched to identify all published RCTs that assessed the effect of RIPC in patients undergoing elective major vascular surgery. Then, we performed a systematic review and meta-analysis to merge the outcomes of RIPC procedures from each RCT, which included all-cause mortality, myocardial infarction (MI), acute kidney injury (AKI), and/or new-onset arrhythmia. RESULTS: A total of 909 patients were enrolled from 10 eligible studies that were conducted from 2007 through 2016. A fixed effect model was utilized in this study to pool each effect size. Pooled analyses of all RCTs showed that RIPC did not reduce the incidence of all-cause mortality (pooled risk ratio [RR] 1.36, 95% confidence interval [CI] 0.63-2.92, P = 0.56), MI (pooled RR 0.77, 95% CI 0.48-1.22, P = 0.38), AKI (pooled RR 0.93, 95% CI 0.68-1.27, P = 0.10), or new-onset arrhythmia (pooled RR 1.47, 95% CI 0.83-2.60, P = 0.52) compared with the control treatment. The publication bias detected by Begg's test was low. CONCLUSIONS: There is no prominent evidence to support the hypothesis that RIPC can provide perioperative protection to patients undergoing elective major vascular surgery. Therefore, the routine use of RIPC to reduce the incidence of perioperative complications of these operations may not be recommended.

Clinical safety of blood flow-restricted training? A comprehensive review of altered muscle metaboreflex in cardiovascular disease during ischemic exercise.

Blood flow restriction training (BFRT) is an increasingly widespread method of exercise that involves imposed restriction of blood flow to the exercising muscle. Blood flow restriction is achieved by inflating a pneumatic pressure cuff (or a tourniquet) positioned proximal to the exercising muscle before, and during, the bout of exercise (i.e., ischemic exercise). Low-intensity BFRT with resistance training promotes comparable increases in muscle mass and strength observed during high-intensity exercise without blood flow restriction. BFRT has expanded into the clinical research setting as a potential therapeutic approach to treat functionally impaired individuals, such as the elderly, and patients with orthopedic and cardiovascular disease/conditions. However, questions regarding the safety of BFRT must be fully examined and addressed before the implementation of this exercise methodology in the clinical setting. In this respect, there is a general concern that BFRT may generate abnormal reflex-mediated cardiovascular responses. Indeed, the muscle metaboreflex is an ischemia-induced, sympathoexcitatory pressor reflex originating in skeletal muscle, and the present review synthesizes evidence that BFRT may elicit abnormal cardiovascular responses resulting from increased metaboreflex activation. Importantly, abnormal cardiovascular responses are more clearly evidenced in populations with increased cardiovascular risk (e.g., elderly and individuals with cardiovascular disease). The evidence provided in the present review draws into question the cardiovascular safety of BFRT, which clearly needs to be further investigated in future studies. This information will be paramount for the consideration of BFRT exercise implementation in clinical populations.

Effect of Blood Flow Restricted Resistance Exercise and Remote Ischemic Conditioning on Functional Capacity and Myocellular Adaptations in Patients With Heart Failure.

BACKGROUND: Patients with congestive heart failure (CHF) have impaired functional capacity and inferior quality of life. The clinical manifestations are associated with structural and functional impairments in skeletal muscle, emphasizing a need for feasible rehabilitation strategies beyond optimal anticongestive medical treatment. We investigated whether low-load blood flow restricted resistance exercise (BFRRE) or remote ischemic conditioning (RIC) could improve functional capacity and quality of life in patients with CHF and stimulate skeletal muscle myofibrillar and mitochondrial adaptations. METHODS: We randomized 36 patients with CHF to BFRRE, RIC, or nontreatment control. BFRRE and RIC were performed 3× per week for 6 weeks. Before and after intervention, muscle biopsies, tests of functional capacity, and quality of life assessments were performed. Deuterium oxide was administered throughout the intervention to measure cumulative RNA and subfraction protein synthesis. Changes in muscle fiber morphology and mitochondrial respiratory function were also assessed. RESULTS: BFRRE improved 6-minute walk test by 39.0 m (CI, 7.0-71.1, P=0.019) compared with control. BFRRE increased maximum isometric strength by 29.7 Nm (CI, 10.8-48.6, P=0.003) compared with control. BFRRE improved quality of life by 5.4 points (CI, -0.04 to 10.9; P=0.052) compared with control. BFRRE increased mitochondrial function by 19.1 pmol/s per milligram (CI, 7.3-30.8; P=0.002) compared with control. RIC did not produce similar changes. CONCLUSIONS: Our results demonstrate that BFRRE, but not RIC, improves functional capacity, quality of life, and muscle mitochondrial function. Our findings have clinical implications for rehabilitation of patients with CHF and provide new insights on the myopathy accompanying CHF. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03380663.

Repetitive vascular occlusion stimulus (RVOS) versus standard care to prevent muscle wasting in critically ill patients (ROSProx):a study protocol for a pilot randomised controlled trial.

BACKGROUND: Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients. METHODS: This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge. DISCUSSION: If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN44340629. Registered on 26 October 2017.

Rationale and Design for the Remote Ischemic Preconditioning for Carotid Endarterectomy Trial.

BACKGROUND: While the perioperative stroke rate after carotid endarterectomy (CEA) is low, "silent" microinfarctions identified by magnetic resonance imaging (MRI) are common and have been correlated with postoperative neurocognitive decline. Our study will investigate the role of remote ischemic preconditioning (RIPC) as a potential neuroprotective mechanism. RIPC is a well-tolerated stimulus that, through neuronal and humoral pathways, generates a systemic environment of greater resistance to subsequent ischemic insults. We hypothesized that patients undergoing RIPC before CEA will have improved postoperative neurocognitive scores compared with those of patients undergoing standard care. METHODS: Patients undergoing CEA will be randomized 1:1 to RIPC or standard clinical care. Those randomized to RIPC will undergo a standard protocol of 4 cycles of RIPC. Each RIPC cycle will involve 5 min of forearm ischemia with 5 min of reperfusion. Forearm ischemia will be induced by a blood pressure cuff inflated to 200 mm Hg or at least 15 mm Hg higher than the systolic pressure if it is >185 mm Hg. This will occur after anesthesia induction and during incision/dissection but before manipulation or clamping of the carotid; thus, patients will be blinded to their assignment. Before carotid endarterectomy, all patients will undergo baseline neurocognitive testing in the form of a Montreal Cognitive Assessment (MoCA) and National Institutes of Health (NIH) Toolbox. MoCA testing only will be conducted on postoperative day 1 in the hospital. The full neurocognitive testing battery will again be conducted at 1-month follow-up in the office. Changes from baseline will be compared between arms at the follow-up time points. Assuming no drop-ins or dropouts and a 10% loss to follow-up, we would need a sample size of 43 patients for 80% power per treatment arm. The primary endpoint, change in MoCA scores, will be analyzed using a random effects model, and secondary outcomes will be analyzed using either linear or logistic regression where appropriate. CONCLUSIONS: RIPC, if shown to be effective in protecting patients from neurocognitive decline after CEA, represents a safe, inexpensive, and easily implementable method of neuroprotection.

The Effect of Remote Ischaemic Preconditioning on Arterial Stiffness in Patients Undergoing Vascular Surgery: A Randomised Clinical Trial.

OBJECTIVES: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on arterial stiffness in patients undergoing vascular surgery. METHODS: This was a randomised, sham controlled, double blind, single centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited. A RIPC or a sham procedure was performed, using a blood pressure cuff, along with preparation for anaesthesia. The RIPC protocol consisting of four cycles of 5 min of ischaemia, followed by 5 min of reperfusion was applied. Arterial stiffness and haemodynamic parameters were measured pre-operatively and 20-28 h after surgery. Two primary outcomes were selected: augmentation index and pulse wave velocity. RESULTS: Ninety-eight patients were randomised. After dropouts 44 and 46 patients were included in the RIPC and sham groups, respectively. Both groups were comparable. There were no statistically significant differences in augmentation index (p = .8), augmentation index corrected for heart rate of 75 beats per minute (p = .8), pulse wave velocity (p = .7), large artery elasticity indices (p = .8), small artery elasticity indices (p = .6), or mean arterial pressure (p = .7) changes between the RIPC and sham groups. There occurred statistically significant (p ≤ .01) improvement in augmentation index (-5.8% vs. -5.5%), augmentation index corrected for a heart rate of 75 beats per minute (-2.5% vs. -2%), small artery elasticity indices (0.7 mL/mmHg × 100 vs. 0.9 mL/mmHg × 100), and mean arterial pressure post-operatively in both the RIPC and the sham groups (change median values in RIPC and sham groups, respectively). CONCLUSIONS: RIPC had no significant effect on arterial stiffness, but there was significant improvement in arterial stiffness after surgery in both groups. Arterial stiffness and haemodynamics may be influenced by surgery or anaesthesia or oxidative stress or all factors combined. Further studies are needed to clarify these findings. CLINICALTRIALS.GOV: NCT02689414.

The effect of repeated remote ischemic postconditioning on infarct size in patients with an ischemic stroke (REPOST): study protocol for a randomized clinical trial.

BACKGROUND: Remote ischemic postconditioning (rIPostC) refers to the observation that repeated, short periods of ischemia protect remote areas against tissue damage during and after prolonged ischemia. Based on previous observations of a potential neuroprotective effect of rIPostC, the aim of this study is to evaluate whether repeated rIPostC after an ischemic stroke can reduce infarct size, which could be translated to an improvement in clinical outcomes. METHODS/DESIGN: We will enroll 200 ischemic stroke patients to daily rIPostC or sham conditioning during hospitalization into a randomized single-blind placebo-controlled trial. The intervention consists of twice daily exposure to four cycles of 5-min cuff inflation around the upper arm to > 20 mmHg above systolic blood pressure (i.e., rIPostC) or 50 mmHg (i.e., control), followed by 5 minutes of deflation. The primary outcome is infarct size, measured using an MRI diffusion-weighted image at the end of hospitalization. Secondary outcomes include the Modified Rankin Scale, National Institutes of Health Stroke Scale, quality of life, and cardiovascular and cerebrovascular morbidity and mortality. To explore possible underlying mechanisms of rIPostC, venous blood will be sampled to assess biomarkers of inflammation and vascular health. DISCUSSION: Previous studies in animals and humans, using a single bout of remote ischemic conditioning, report a potential effect of rIPostC in attenuating neural damage. Although repeated rIPostC has been investigated for cardiovascular disease patients and preclinical stroke models, no previous study has explored the potential physiological and clinical effects of repeatedly applying rIPostC during the hospitalization phase after a stroke. TRIAL REGISTRATION: Netherlands Trial Register, NTR6880 . Registered on 8 December 2017.

Punctal and canalicular plugs: Indications, efficacy and safety.

Lacrimal occlusion with punctal or canalicular plugs have been used to treat dry eye disease for more than 40 years. Indeed, punctal plugs constitute a safe and effective tool to retain the natural tear film and prolong the effect of tear substitutes. A wide variety of plugs is available, differing in their design, location (punctal versus canalicular) and their resorbability. There indications have increasingly broadened, and they are now one of the treatment options for numerous ocular surface diseases. Current research focuses on using punctal plugs for extended delivery of drugs to the ocular surface. This review addresses physiology of lacrimal drainage, available models of punctal plugs, their indications, practical details of prescribing and placing punctal and canalicular plugs, and possible complications.

Chronic remote ischemic preconditioning-induced increase of circulating hSDF-1α level and its relation with reduction of blood pressure and protection endothelial function in hypertension.

Although previous data showed that remote ischemic preconditioning (RIPC) has beneficial effect on blood pressure (BP) reduction, the efficacy of RIPC-induced decline in BP and the favorable humoral factors in hypertension is elusive. This present study is performed to evaluate whether RIPC reduces BP, improves microvascular endothelial function and increases circulating hSDF-1α generation in hypertension. Fifteen hypertensive patients received 3 periods of 5-min inflation/deflation of the forearm with a cuff on the upper arm daily for 30 days. Clinic and 24-h ambulatory blood pressure monitoring (ABPM) were examined before and after the end of this procedure. Microvascular endothelial function was measured by finger reactive hyperemia index (RHI) using the Endo-PAT 2000 device. The circulating hSDF-1α level was tested by ELISA. RIPC significantly decreased systolic BP (139.13 ± 6.68 versus 131.45 ± 7.45 mmHg) and diastolic BP (89.67 ± 4.98 versus 83.83 ± 6.65 mmHg), meanwhile 24-h ambulatory systolic and diastolic BP dropped from 136.33 ± 9.10 mmHg to 131.33 ± 7.12 mmHg and 87.60 ± 6.22 mmHg to 82.47 ± 4.47 mmHg respectively. RHI was improved (1.95 ± 0.34 versus 2.47 ± 0.44). Plasma hSDF-1α level was markedly increased after RIPC (1585.86 ± 167.17 versus 1719.54 ± 211.17 pg/ml). The increase in hSDF-1α level was associated with the fall in clinic and 24-h ABPM and rise in RHI. The present data suggests that RIPC may be a novel alternative or complementary intervention means to treat hypertension and protect endothelial function.

Is surgical parent artery occlusion effective for intracranial aneurysms measuring over 10 mm in size? Result from long-term follow-up of size changes and outcomes.

BACKGROUND: There have been no long-term follow-up reports pertaining to chronological size changes in large or giant unruptured intracranial aneurysms treated with surgical parent artery occlusion (PAO). The object of this study is to investigate the utility and safety of surgical PAO by conducting a long-term follow-up of chronological aneurysm size changes and outcomes. METHODS: A retrospective study of 21 unruptured intracranial aneurysms measuring over 10 mm (20 patients) treated with surgical PAO in the period 2012-2017 was conducted. For aneurysms presenting with anterior circulation, high/low flow bypass was chosen and carried out concomitantly on the basis of preoperative balloon occlusion test results. Aneurysm size before and after surgery was evaluated chronologically using maximum diameter measurements taken from the same slice of MRI T2-weighted images. Moreover, post-surgery outcomes were evaluated according to a modified Rankin scale (mRS) at discharge. RESULTS: PAO aiming for blind-alley formation was performed in 20 of 21 aneurysms (95.2%). Aneurysm size reduction was confirmed in 20 aneurysms (95.2%) after proper PAO, with an average reduction rate of 63.1% (range, 28-95%), during an average follow-up period of 27 months (range, 4-54 months). Eighteen (90.4%) of the 20 patients with 21 aneurysms returned to previous life with mRS score 0-2. With regard to preoperative symptoms, diplopia and visual impairment had improved in three patients (50%) and one patient (100%), respectively. Ischemic complications had occurred in five patients, two (9.6%) of whom were symptomatic and three (14.3%) were asymptomatic. The mortality rate in this study was 0%. CONCLUSIONS: Surgical PAO for unruptured intracranial aneurysms measuring over 10 mm has been shown to be an effective method of treatment, eliciting a reduction in aneurysm size.

Impact of remote ischemic preconditioning preceding coronary artery bypass grafting on inducing neuroprotection.

BACKGROUND: Neurological complications after coronary artery bypass grafting (CABG) reduce quality of life, increase mortality, and inflate resource utilization. The risk of postoperative neurological complications parallels the increasing risk burden of the contemporary patient population. We evaluated the efficacy of remote ischemic preconditioning (RIPC) on inducing neuroprotection. METHODS: Seventy patients undergoing first-time CABG were randomly assigned to RIPC or a sham procedure. Structural brain magnetic resonance imaging (MRI) was complemented with functional connectivity MRI to gain a whole-brain global connectivity analysis. Paired neurocognitive and MRI data were acquired pre- and postoperatively. The primary end point was a composite of new ischemic brain lesions and neurocognitive impairment. Secondary end points included brain connectivity profiles, pooled ischemic volumes, and individual components of the primary outcome. The Shapiro-Wilk test was used to determine whether a data set followed a normal distribution. The Fisher exact test was used to calculate the measures of association for categorical variables, whereas continuous data were tested with either the Mann-Whitney U test or the Student t test. RESULTS: There was no between-group difference in the incidence of the primary end point (9 [27%] in the RIPC group vs 8 [24%] in the control group, odds ratio, 1.17 [95% confidence interval, 0.34-4.06]; P = 1.0). Although RIPC did not reduce the incidence of brain ischemia (8/33 [24%] vs 7/33 [21%]; P = 1.0), the pooled ischemic volume was lower in the RIPC group (157 [interquartile range, 125-231] vs 777 [interquartile range, 564-965] mm3; P = .004). Postoperative neurocognition was marginally superior in the RIPC group as evidenced by a lower absolute number of abnormal neurocognitive tests in the RIPC group (7/99 [7%] vs 16/99 [16%]; odds ratio, 0.40 [95% confidence interval, 0.14-1.09]; P = .074). Robust reductions of functional connectivity profiles for the associative thalamus were documented in both groups, irrespective of RIPC (RIPC group, t = 3.31; P < .01; and the control group, t = 3.52; P < .01). CONCLUSIONS: Silent brain ischemia occurs frequently after CABG. RIPC did not reduce the incidence of the primary outcome. However, RIPC significantly reduced the pooled volume of ischemic brain lesions. Surgery adversely affected global brain connectivity, with RIPC conferring no demonstrable protection. The association of RIPC with superior neurocognitive test scores failed to cross the threshold for significance.

Effect of Repeated Remote Ischemic Preconditioning on Peripheral Arterial Disease in Patients Suffering from Intermittent Claudication.

BACKGROUND/OBJECTIVE: Intermittent claudication (IC) is the symptom of peripheral artery disease (PAD) and causes functional disability. Remote ischemic preconditioning (RIPC), is a phenomenon in which a short period of sub-critical ischemia, protects tissues against ischemia/reperfusion/injury. We considered to test the hypothesis that RIPC in PAD patients suffering from IC would increase muscle resistance to ischemia and thus improve walking-capacity. MATERIALS/METHODS: A total of 63 patients with proven-IC underwent two treadmill tests (graded treadmill protocol) with a 28-day interval in between. Patients were consecutively assigned for the non/RIPC-group and RIPC-group procedure one by one. Patients received 5-cycles of alternating 5-minute inflation and 5-minute deflation of blood-pressure cuffs on nondominant upper-limb every day for four weeks. Initial claudication distance (ICD), total walking distance (TWD) and time to relief of claudication (TRC) were recorded during procedure. RESULTS: Patients receiving-RIPC exhibited a marked increase in ICD and TWD between basal and last tests: 209.1 ± 15.4 m vs. 226 ± 15.0 m and 368.8 ± 21.0 m vs. 394 ± 19.9 m, respectively (p < 0.001). In addition, patients receiving-RIPC represented a significant decrease in TRC between basal and last tests: 7.8 ± 1.3 min vs. 6.4 ± 1.1 min, respectively (p < 0.001). Patients not receiving-RIPC did not exhibit improvement in ICD, TWD, and TRC between basal and last tests: 205.2 ± 12.1 min vs. 207.4 ± 9.9 min, 366.5 ± 24.2 min vs. 369.4 ± 23.2 min and 7.9 ± 1.4 min vs. 7.7 ± 1.3 min, respectively (p > 0.05). CONCLUSION: A significant increase in ICD and TWD were observed in last/treadmill test in RIPC-group. In addition, a significant decrease in TRC was observed in last/treadmill test in RIPC-group. In non/RIPC-group, no improvement was observed in ICD, TWD and TRC.

Moderately heavy exercise produces lower cardiovascular, RPE, and discomfort compared to lower load exercise with and without blood flow restriction.

PURPOSE: To determine the acute cardiovascular and perceptual responses of low-load exercise with or without blood flow restriction and compare those responses to that of moderately heavy exercise. METHODS: Twenty-two participants completed unilateral elbow flexion exercise with a moderately heavy-load- [70% one-repetition maximum (1RM); 70/0] and with three low-load conditions (15% 1RM) in combination with 0% (15/0), 40%, (15/40) and 80% (15/80) arterial occlusion pressure. Participants exercised until failure (or until 90 repetitions per set). The cardiovascular response (arterial occlusion) was measured pre and post exercise and the perceptual responses [ratings of perceived exertion (RPE) and discomfort] were determined before and after each set of exercise. RESULTS: For arterial occlusion pressure, the lower-load conditions had greater change from pre to post compared to 70/00 (e.g., 15/80: 44 vs. 70/0: 34 mmHg). RPE was highest across the sets for the 15/80 condition with the other conditions having similar RPE (e.g., set 4: median rating of 17.2 for 15/80 vs. ~ 15.5 for other conditions). Ratings of discomfort were also greatest for the 15/80 condition (15/80 > 15/40 > 15/0 > 70/0). Exercise volume within the 15/0 and 15/40 conditions were similar but were significantly greater than that observed with the 15/80 and 70/0 conditions. CONCLUSION: Low-load exercise to volitional failure results in a greater cardiovascular response to that of moderately heavy-load exercise. When high pressure is applied to low load exercise, there is a reduction in exercise volume but an elevated perceptual response that may be an important consideration when applying this stimulus in practice.

Incidence, Characteristics, and Clinical Course of Device-Related Thrombus After Watchman Left Atrial Appendage Occlusion Device Implantation in Atrial Fibrillation Patients.

OBJECTIVES: This study investigated characteristics and clinical impact of device-related thrombus formation after Watchman device implantation in atrial fibrillation (AF) patients. BACKGROUND: Left atrial appendage occlusion using the Watchman device is an effective alternative to anticoagulation for stroke prevention in AF patients. However, device-related thrombus formation remains an important concern after Watchman implantation. METHODS: From 2006 to 2014, 119 consecutive AF patients underwent Watchman implantation. Transesophageal echocardiographic (TEE) follow-up was scheduled at 45 days, at 6 months, and at 12 months after the procedure. The incidence, characteristics, and clinical course of device-related thrombus formation detected by TEE were assessed. RESULTS: Follow-up TEE identified thrombus formation on the Watchman device in 4 patients (3.4%). The prevalence of chronic AF was 100% in patients with thrombus, which was higher than that for patients without thrombus (40.0%). Deployed device size was numerically larger in patients with thrombus (29.3 ± 3.8 mm vs. 25.7 ± 3.2 mm, respectively). All patients with thrombus discontinued any of the anticoagulant/antiplatelet therapy which was required under the study protocol. After restarting or continuing warfarin and aspirin therapy, complete resolution of the thrombus was achieved in all patients at subsequent follow-up TEE. Warfarin therapy was discontinued within 6 months for all cases, and there was no thrombus recurrence. The mean follow-up duration was 1,456 ± 546 days, with no death, stroke, or systemic embolization events in patients with thrombus. CONCLUSIONS: AF burden, device size, and anticoagulant/antiplatelet regimens can be associated with device-related thrombus after Watchman device implantation. Short-term warfarin therapy was effective, and the clinical outcomes were favorable.

Umbilical Cord Occlusion via Laser Coagulation in Monochorionic Multifetal Gestations before and after 20 Weeks of Gestation.

INTRODUCTION: Umbilical cord occlusion (UCO) utilizing laser photocoagulation is often not considered an option for selective termination after 20 weeks of gestation due to reported limitations of the procedure because of umbilical cord size. We compared outcomes after laser umbilical cord occlusion (L-UCO) before and after 20 weeks of gestation. MATERIALS AND METHODS: We examined all patients with monochorionic- diamniotic twins and higher-order multiples (monoamniotic excluded) that underwent L-UCO at our facility between 2006 and 2014. Statistical analysis was performed using Fisher's exact and Kruskal-Wallis tests as appropriate. RESULTS: Of 43 L-UCO cases, 11 cases (25.6%) had a discordant anomaly, and 32 cases (74.4%) had twin reversed arterial perfusion (TRAP) sequence. We achieved complete vascular occlusion in 100% (43/43) of cases of attempted L-UCO. There were 22 cases (51.2%) with gestational age ≤20 weeks, and 21 cases (48.8%) with gestational age >20 weeks. Perioperative patient characteristics and outcomes did not differ between the two groups. Survival rates were 90.9% (20/22) and 100% (21/21) at ≤20 weeks of gestation and >20 weeks of gestation, respectively. DISCUSSION: The results of this study suggest that L-UCO is a reasonable surgical modality for patients prior to and beyond 20 weeks of gestation.

Pulmonary Hypertension and Atrial Septal Defect: Management Dilemma.

The decision making in patients with an atrial septal defect (ASD) in setting of pulmonary hypertension is complex. In the era of pulmonary arterial vasodilator therapy, every patient should undergo evaluation by pulmonary hypertension experts especially if defect closure is being considered. Defect closure in the inappropriate group can lead to poor outcomes.