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First-degree atrioventricular (AV) block (PR interval >200 ms) is commonly observed among screening electrocardiogram (ECG) in athletes. Profound first-degree AV block (PR interval >400 ms) and Mobitz type I (Wenckebach) second-degree AV block are generally uncommon and often require further workup on a case-by-case basis, particularly when there is concern for a structural cardiac abnormality. In this case, we present an example of an asymptomatic profound first-degree AV block with Mobitz type I (Wenckebach) second-degree AV block. Transthoracic echocardiogram and stress echocardiogram were unremarkable and the patient was cleared to participate in sports without any restriction. Physicians managing athletes should be aware of ECG features that require additional evaluation and cardiology consultation., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Aim: The "2024 Guideline for the Primary Prevention of Stroke" replaces the 2014 "Guidelines for the Primary Prevention of Stroke." This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke., Methods: A comprehensive search for literature published since the 2014 guideline; derived from research involving human participants published in English; and indexed in MEDLINE, PubMed, Cochrane Library, and other selected and relevant databases was conducted between May and November 2023. Other documents on related subject matter previously published by the American Heart Association were also reviewed., Structure: Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable. The 2024 primary prevention of stroke guideline provides recommendations based on current evidence for strategies to prevent stroke throughout the life span. These recommendations align with the American Heart Association's Life's Essential 8 for optimizing cardiovascular and brain health, in addition to preventing incident stroke. We also have added sex-specific recommendations for screening and prevention of stroke, which are new compared with the 2014 guideline. Many recommendations for similar risk factor prevention were updated, new topics were reviewed, and recommendations were created when supported by sufficient-quality published data.

Competing Interests: None.

Exercise testing is frequently incorporated into management of patients with cardiovascular and/or pulmonary disease. A lifelong commitment to exercise promotes cardiac remodeling, leading to changes in structure and function of the atria and ventricles, commonly referred to as the "athletic heart." Stress testing is also incorporated into the management of athletes for a variety of reasons, such as identifying the cause of exertional symptoms, determining level of fitness and training zones, or assessing for acquired cardiomyopathies. Exercise testing should be tailored to the athlete, since performance may vary from other populations as a result of a commitment to exercise training., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Identification of long-term calcium channel blocker (CCB) responders with acute vasodilator challenge is critical in the evaluation of patients with pulmonary arterial hypertension. Currently there is no standardized approach for use of supplemental oxygen during acute vasodilator challenge. In this retrospective analysis of patients identified as acute vasoresponders, treated with CCBs, all patients had hemodynamic measurements in three steps: (1) at baseline; (2) with 100% fractional inspired oxygen; and (3) with 100% fractional inspired oxygen plus inhaled nitric oxide (iNO). Those meeting the definition of acute vasoresponsiveness only after first normalizing for the effects of oxygen in step 2 were labeled "iNO Responders." Those who met the definition of acute vasoresponsiveness from a combination of the effects of 100% FiO 2 and iNO were labeled "oxygen responders." Survival, hospitalization for decompensated right heart failure, duration of CCB monotherapy, and functional data were collected. iNO responders, when compared to oxygen responders, had superior survival (100% vs. 50.1% 5-year survival, respectively), fewer hospitalizations for acute decompensated right heart failure (0% vs. 30.4% at 1 year, respectively), longer duration of CCB monotherapy (80% vs. 52% at 1 year, respectively), and superior 6-min walk distance. Current guidelines for acute vasodilator testing do not standardize oxygen coadministration with iNO. This study demonstrates that adjusting for the effects of supplemental oxygen before assessing for acute vasoresponsiveness identifies a cohort with superior functional status, tolerance of CCB monotherapy, and survival while on long-term CCB therapy., Competing Interests: We have no financial disclosures or conflicts of interest to report., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Patients with heart failure with reduced ejection fraction (HFrEF) have persistent impairments in functional capacity after continuous-flow left ventricular assist device (CF-LVAD) implantation., Objectives: This study aims to characterize longitudinal changes in exercise hemodynamics and functional capacity among patients with HFrEF before and after CF-LVAD implantation., Methods: Ten patients underwent 3 invasive cardiopulmonary exercise tests on upright cycle ergometry with pulmonary artery catheterization: 1) Visit 1 before CF-LVAD implantation; 2) Visit 2 after device implantation with CF-LVAD pump speed held constant at baseline speed; and 3) Visit 3 with increases in pump speed during exercise (median: 1,050 rpm [IQR: 750-1,150 rpm] and 220 rpm [IQR: 120-220 rpm] for HeartMate 3 and HeartWare VAD, respectively). Hemodynamics and direct Fick cardiac output were monitored using pulmonary artery catheterization. Gas exchange metrics were determined using indirect calorimetry., Results: Maximal oxygen uptake (Visits 1, 2, and 3: 10.8 ± 2.5 mL/kg/min, 10.7 ± 2.2 mL/kg/min, and 11.5 ± 1.7 mL/kg/min; P = 0.92) did not improve after device implantation. Mean pulmonary arterial and pulmonary capillary wedge pressures increased significantly during submaximal and peak exercise on preimplantation testing (P < 0.01 for rest vs peak exercise) and remained elevated, with minimal change on Visits 2 and 3 regardless of whether pump speed was fixed or increased., Conclusions: Among patients with HFrEF, cardiovascular hemodynamics and exercise capacity were similar after CF-LVAD implantation, regardless of whether patients exercised at fixed or adjusted pump speeds during exercise. Further research is needed to determine methods by which LVADs may alleviate the HFrEF syndrome after device implantation. (Effect of mechanIcal circulatoRy support ON exercise capacity aMong pAtieNts with heart failure [IRONMAN]; NCT03078972)., Competing Interests: Funding Support and Author Disclosures Dr Cornwell has received funding by an National Institutes of Health/National Heart, Lung and Blood Institute Mentored Patient-Oriented Research Career Development Award (#1K23HLI32048-01), as well as the National Institutes of Health/National Center for Advancing Translational Sciences (#UL1TR002535), the Clinical Translational Science Institute at the University of Colorado Anschutz Medical Campus, and Medtronic Inc. Dr Allen has received consulting fees from Boston Scientific, Medtronic, Abbott, ACI Clinical, Amgen, Cytokinetics, and Novartis. Dr Cornwell has received research funding from Merck Corp and Medtronic Inc; and is a consultant for Merck Corp, Medtronic Inc, and Bioventrix Inc. All other author have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The post-acute sequalae of SARS-CoV-2, also known as "Long COVID," is characterized by profound fatigue, impaired functional capacity with post-exertional malaise, orthostatic intolerance, and tachycardia. At least 25-30% of individuals impacted by SARS-CoV-2 will go on to experience the Long COVID syndrome, underscoring the detrimental impact this condition has on society. Although efforts are underway to further understand risk factors for Long COVID and identify strategies to prevent disease development entirely, implementation of treatment strategies is warranted to alleviate symptom burden among those affected. This review provides a rationale for exercise prescriptions tailored to the Long COVID patient based on the pathophysiology underlying this syndrome, as well as the previously demonstrated benefits of exercise training in other similar populations whose clinical manifestations result from cardiac deconditioning. Herein, we discuss methods to tailor exercise protocols, accommodating exercise intolerance and post-exertional malaise that may otherwise limit the ability to participate in a training protocol, as well as data demonstrating that a focused exercise prescription may effectively alleviate symptom burden in these patients. Long COVID results, in large part, from deconditioning, which may result from as little as 20 hr of inactivity. Exercise prescriptions tailored to patients with Long COVID may effectively alleviate symptom burden associated with this condition and in the absence of overt contraindications should be considered in management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF), but quantitative data regarding exertional hemodynamics are lacking., Objectives: We sought to characterize exertional cardiopulmonary hemodynamics in patients with HFrEF., Methods: We studied 35 patients with HFrEF (59 ± 12 years old, 30 males) who completed invasive cardiopulmonary exercise testing. Data were collected at rest, at submaximal exercise and at peak effort on upright cycle ergometry. Cardiovascular and pulmonary vascular hemodynamics were recorded. Fick cardiac output (Qc) was determined. Hemodynamic predictors of peak oxygen uptake (VO 2 ) were identified., Results: Left ventricular ejection fraction and cardiac index were 23% ± 8% and 2.9 ± 1.1 L/min/m 2 , respectively. Peak VO 2 was 11.8 ± 3.3 mL/kg/min, and the ventilatory efficiency slope was 53 ± 13. Right atrial pressure increased from rest to peak exercise (4 ± 5 vs 7 ± 6 mmHg,). Mean pulmonary arterial pressure increased from rest to peak exercise (27 ± 13 vs 38 ± 14 mmHg). Pulmonary artery pulsatility index increased from rest to peak exercise, while pulmonary arterial capacitance and pulmonary vascular resistance declined., Conclusions: Patients with HFrEF suffer from marked increases in filling pressures during exercise. These findings provide new insight into cardiopulmonary abnormalities contributing to impairments in exercise capacity in this population., Clinical Trial Registration: clinicaltrials.gov identifier: NCT03078972., Competing Interests: Disclosures None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Topic Importance: Right ventricular dysfunction in pulmonary hypertension (PH) contributes to reduced exercise capacity, morbidity, and mortality. Exercise can unmask right ventricular dysfunction not apparent at rest, with negative implications for prognosis., Review Findings: Among patients with pulmonary vascular disease, right ventricular afterload may increase during exercise out of proportion to increases observed among healthy individuals. Right ventricular contractility must increase to match the demands of increased afterload to maintain ventricular-arterial coupling (the relationship between contractility and afterload) and ultimately cardiac output. Impaired right ventricular contractile reserve leads to ventricular-arterial uncoupling, preventing cardiac output from increasing during exercise and limiting exercise capacity. Abnormal pulmonary vascular response to exercise can signify early pulmonary vascular disease and is associated with increased mortality. Impaired right ventricular contractile reserve similarly predicts poor outcomes, including reduced exercise capacity and death. Exercise provocation can be used to assess pulmonary vascular response to exercise and right ventricular contractile reserve. Noninvasive techniques (including cardiopulmonary exercise testing, transthoracic echocardiography, and cardiac MRI) as well as invasive techniques (including right heart catheterization and pressure-volume analysis) may be applied selectively to the screening, diagnosis, and risk stratification of patients with suspected or established PH. Further research is required to determine the role of exercise stress testing in the management of pulmonary vascular disease., Summary: This review describes the current understanding of clinical applications of exercise testing in the risk assessment of patients with suspected or established PH., (Copyright © 2023 American College of Chest Physicians. All rights reserved.)

Cardiac rehabilitation has strong evidence of benefit across many cardiovascular conditions but is underused. Even for those patients who participate in cardiac rehabilitation, there is the potential to better support them in improving behaviors known to promote optimal cardiovascular health and in sustaining those behaviors over time. Digital technology has the potential to address many of the challenges of traditional center-based cardiac rehabilitation and to augment care delivery. This American Heart Association science advisory was assembled to guide the development and implementation of digital cardiac rehabilitation interventions that can be translated effectively into clinical care, improve health outcomes, and promote health equity. This advisory thus describes the individual digital components that can be delivered in isolation or as part of a larger cardiac rehabilitation telehealth program and highlights challenges and future directions for digital technology generally and when used in cardiac rehabilitation specifically. It is also intended to provide guidance to researchers reporting digital interventions and clinicians implementing these interventions in practice and to advance a framework for equity-centered digital health in cardiac rehabilitation.

A 37-year-old athlete completed invasive endurance (90 km) bicycle exercise testing for right ventricular pressure-volume analysis. Increased right ventricular afterload caused declines in ventricular-arterial coupling and cardiac output, causing increased arteriovenous oxygen difference to maintain oxygen uptake. These findings demonstrate effects of changes in right ventricular performance on exercise capacity. ( Level of Difficulty: Intermediate. )., Competing Interests: Dr Cornwell has received funding by a National Institutes of Health/National Heart, Lung, and Blood Institute Mentored Patient-Oriented Research Career Development Award (1K23HLI32048), as well as the National Institutes of Health/National Center for Advancing Translational Sciences (UL1TR002535). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Approximately 6 million individuals have heart failure in the United States alone and 15 million in Europe. Left ventricular assist devices (LVAD) improve survival in these patients, but functional capacity may not fully improve. This article examines the hypothesis that patients supported by LVAD experience persistent reductions in functional capacity and explores mechanisms accounting for abnormalities in exercise tolerance., (Copyright © 2022 by the American College of Sports Medicine.)

Left ventricular assist-device (LVAD) implantation is a life-saving therapy for patients with advanced heart failure (HF). With chronic unloading and circulatory support, LVAD-supported hearts often show significant reverse remodeling at the structural, cellular and molecular level. However, translation of these changes into meaningful cardiac recovery allowing LVAD explant is lagging. Part of the reason for this discrepancy is lack of anticipation and hence promotion and evaluation for recovery post LVAD implant. There is additional uncertainty about the long-term course of HF following LVAD explant. In selected patients, however, guided by the etiology of HF, duration of disease and other clinical factors, significant functional improvement and LVAD explantation with long-term freedom from recurrent HF events has been demonstrated to be feasible in a reproducible manner. The identified predictors of myocardial recovery suggest that the elective therapeutic use of potentially less invasive VADs for reversal of HF earlier in the disease process is a future goal that warrants further investigation. Hence, it is prudent to develop and implement tools to predict HF reversibility prior to LVAD implant, optimize unloading-promoted recovery with guideline directed medical therapy and monitor for myocardial improvement. This review article summarizes the clinical aspects of myocardial recovery and together with its companion review article focused on the biological aspects of recovery, they aim to provide a useful framework for clinicians and investigators., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Passive hot water immersion (PHWI) provides a peripheral vasculature shear stimulus comparable to low-intensity exercise within the active skeletal muscle, whereas moderate- and high-intensity exercise elicit substantially greater shear rates in the peripheral vasculature, likely conferring greater vascular benefits. Notably, few studies have compared postintervention shear rates in the peripheral and cerebral vasculature after high-intensity exercise and PHWI, especially considering that the postintervention recovery period represents a key window in which adaptation occurs. Therefore, we aimed to compare shear rates in the internal carotid artery (ICA), vertebral artery (VA), and common femoral artery (CFA) between high-intensity exercise and whole body PHWI for up to 80 min after intervention. Fifteen healthy (27 ± 4 yr), moderately trained individuals underwent three time-matched interventions in a randomized order that included 30 min of whole body immersion in a 42°C hot bath, 30 min of treadmill running and 5 × 4-min high-intensity intervals (HIIE). There were no differences in ICA ( P = 0.4643) and VA ( P = 0.1940) shear rates between PHWI and exercise (both continuous and HIIE) after intervention. All three interventions elicited comparable increases in CFA shear rate after intervention ( P = 0.0671); however, CFA shear rate was slightly higher 40 min after threshold running ( P = 0.0464) and slightly higher, although not statistically, for HIIE ( P = 0.0565) compared with PHWI. Our results suggest that time- and core temperature-matched high-intensity exercise and PHWI elicit limited changes in cerebral shear and comparable increases in peripheral vasculature shear rates when measured for up to 80 min after intervention. NEW & NOTEWORTHY The study aimed to compare shear rates in lower limb and extracranial cerebral blood vessels for up to 80 min after high-intensity exercise and whole body passive hot water immersion (PHWI). Time- and core temperature-matched high-intensity exercise and whole body PHWI both elicited minimal, but comparable, postintervention changes in cerebral artery shear rate. Furthermore, 30 min of PHWI caused a postintervention increase in femoral shear rate similar to high-intensity exercise; however, femoral shear remained slightly elevated for a longer period after high-intensity exercise. These results suggest that PHWI provides postintervention changes in lower limb peripheral shear rates comparable to intense exercise and is likely a therapeutic alternative in individuals unable to perform exercise.

Ischemic heart disease and stroke are the number 1 and number 2 causes of death worldwide, respectively. A lifelong commitment to exercise reduces the risk of these adverse events and is also associated with several cardiometabolic improvements, including reductions in blood pressure, cholesterol, and inflammatory markers, as well as improved glucose control. Routine exercise also reduces the risk of developing comorbidities that increase the risk of cardiovascular or cerebrovascular disease. While the benefits of a lifelong commitment to exercise are well documented, there is a complex interaction between exercise and stroke risk, such that the risk of ischemic or hemorrhagic stroke may increase acutely during or immediately following exercise. In this article, we discuss the physiological responses to different types of exercise, as well as the determinants of resting and exertional cerebrovascular perfusion, and explore the complex interaction between atrial fibrillation, exercise, and stroke risk. Finally, we highlight the increased risk of stroke during different types of exercise, as well as factors that may alleviate this risk.

Right ventricular pressure-volume (PV) analysis characterizes ventricular systolic and diastolic properties independent of loading conditions like volume status and afterload. While long-considered the gold-standard method for quantifying myocardial chamber performance, it was traditionally only performed in highly specialized research settings. With recent advances in catheter technology and more sophisticated approaches to analyze PV data, it is now more commonly used in a variety of clinical and research settings. Herein, we review the basic techniques for PV loop measurement, analysis, and interpretation with the aim of providing readers with a deeper understanding of the strengths and limitations of PV analysis. In the second half of the review, we detail key scenarios in which right ventricular PV analysis has influenced our understanding of clinically relevant topics and where the technique can be applied to resolve additional areas of uncertainty. All told, PV analysis has an important role in advancing our understanding of right ventricular physiology and its contribution to cardiovascular function in health and disease.

An increasing number of individuals travel to mountainous environments for work and pleasure. However, oxygen availability declines at altitude, and hypoxic environments place unique stressors on the cardiovascular system. These stressors may be exacerbated by exercise at altitude, because exercise increases oxygen demand in an environment that is already relatively oxygen deplete compared with sea-level conditions. Furthermore, the prevalence of cardiovascular disease, as well as diseases such as hypertension, heart failure, and lung disease, is high among individuals living in the United States. As such, patients who are at risk of or who have established cardiovascular disease may be at an increased risk of adverse events when sojourning to these mountainous locations. However, these risks may be minimized by appropriate pretravel assessments and planning through shared decision-making between patients and their managing clinicians. This American Heart Association scientific statement provides a concise, yet comprehensive overview of the physiologic responses to exercise in hypoxic locations, as well as important considerations for minimizing the risk of adverse cardiovascular events during mountainous excursions.

The Society of Thoracic Surgeons (STS)-Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 2020 Annual Report reviews outcomes on 25,551 patients undergoing primary isolated continuous-flow left ventricular assist device (LVAD) implantation between 2010 and 2019. In 2019, 3198 primary LVADs were implanted, which is the highest annual volume in Intermacs history. Compared with the previous era (2010-2014), patients who received an LVAD in the most recent era (2015-2019) were more likely to be African American (26.8% vs 22.9%, P < .0001) and more likely to be bridged to durable LVAD with temporary mechanical support devices (36.8% vs 26.0%, P < .0001). In 2019, 50% of patients were INTERMACS Profile 1 or 2 before durable LVAD, and 73% received an LVAD as destination therapy. Magnetic levitation technology has become the predominant design, accounting for 77% of devices in 2019. The 1- and 2-year survival in the most recent era has improved compared with 2010 to 2014 (82.3% and 73.1% vs 80.5% and 69.1%, respectively; P < .0001). Major bleeding and infection continue to be the leading adverse events. Incident stroke has declined in the current era to 12.7% at 1 year. STS-Intermacs research publications are highlighted, and the new quality initiatives are introduced., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with continuous-flow left ventricular assist devices (CF-LVADs) experience limitations in functional capacity and frequently, right ventricular (RV) dysfunction. We sought to characterize RV function in the context of global cardiopulmonary performance during exercise in this population., Methods: A total of 26 patients with CF-LVAD (aged 58 ± 11 years, 23 males) completed a hemodynamic assessment with either conductance catheters (Group 1, n = 13) inserted into the right ventricle to generate RV pressure‒volume loops or traditional Swan‒Ganz catheters (Group 2, n = 13) during invasive cardiopulmonary exercise testing. Hemodynamics were collected at rest, 2 sub-maximal levels of exercise, and peak effort. Breath-by-breath gas exchange parameters were collected by indirect calorimetry. Group 1 participants also completed an invasive ramp test during supine rest to determine the impact of varying levels of CF-LVAD support on RV function., Results: In Group 1, pump speed modulations minimally influenced RV function. During upright exercise, there were modest increases in RV contractility during sub-maximal exercise, but there were no appreciable increases at peak effort. Ventricular‒arterial coupling was preserved throughout the exercise. In Group 2, there were large increases in pulmonary arterial, left-sided filling, and right-sided filling pressures during sub-maximal and peak exercises. Among all participants, the cardiac output‒oxygen uptake relationship was preserved at 5.8:1. Ventilatory efficiency was severely abnormal at 42.3 ± 11.6., Conclusions: Patients with CF-LVAD suffer from limited RV contractile reserve; marked elevations in pulmonary, left-sided filling, and right-sided filling pressures during exercise; and severe ventilatory inefficiency. These findings explain mechanisms for persistent reductions in functional capacity in this patient population., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Spaceflight-associated neuro-ocular syndrome (SANS) involves unilateral or bilateral optic disc edema, widening of the optic nerve sheath, and posterior globe flattening. Owing to posterior globe flattening, it is hypothesized that microgravity causes a disproportionate change in intracranial pressure (ICP) relative to intraocular pressure. Countermeasures capable of reducing ICP include thigh cuffs and breathing against inspiratory resistance. Owing to the coupling of central venous pressure (CVP) and intracranial pressure, we hypothesized that both ICP and CVP will be reduced during both countermeasures. In four male participants (32 ± 13 yr) who were previously implanted with Ommaya reservoirs for treatment of unrelated clinical conditions, ICP was measured invasively through these ports. Subjects were healthy at the time of testing. CVP was measured invasively by a peripherally inserted central catheter. Participants breathed through an impedance threshold device (ITD, -7 cmH 2 O) to generate negative intrathoracic pressure for 5 min, and subsequently, wore bilateral thigh cuffs inflated to 30 mmHg for 2 min. Breathing through an ITD reduced both CVP (6 ± 2 vs. 3 ± 1 mmHg; P = 0.02) and ICP (16 ± 3 vs. 12 ± 1 mmHg; P = 0.04) compared to baseline, a result that was not observed during the free breathing condition (CVP, 6 ± 2 vs. 6 ± 2 mmHg, P = 0.87; ICP, 15 ± 3 vs. 15 ± 4 mmHg, P = 0.68). Inflation of the thigh cuffs to 30 mmHg caused no meaningful reduction in CVP in all four individuals (5 ± 4 vs. 5 ± 4 mmHg; P = 0.1), coincident with minimal reduction in ICP (15 ± 3 vs. 14 ± 4 mmHg; P = 0.13). The application of inspiratory resistance breathing resulted in reductions in both ICP and CVP, likely due to intrathoracic unloading. NEW & NOTEWORTHY Spaceflight causes pathological changes in the eye that may be due to the absence of gravitational unloading of intracranial pressure (ICP) under microgravity conditions commonly referred to as spaceflight-associated neuro-ocular syndrome (SANS), whereby countermeasures aimed at lowering ICP are necessary. These data show that impedance threshold breathing acutely reduces ICP via a reduction in central venous pressure (CVP). Whereas, acute thigh cuff inflation, a popular known spaceflight-associated countermeasure, had little effect on ICP and CVP.

Background: Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation., Methods: Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30 o and 60 o . Heart rate and BP were monitored during cardiopulmonary exercise testing., Results: Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing., Conclusions: Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

Continuous-flow left ventricular assist devices are frequently used for management of patients with advanced heart failure with reduced ejection fraction. Although technologic advancements have contributed to improved outcomes, several complications arise over time. These complications result from several factors, including medication effects, physiologic responses to chronic exposure to circulatory support that is minimally/entirely nonpulsatile, and dysfunction of the device itself. Clinical presentation can range from chronic and indolent to acute, life-threatening emergencies. Several areas of uncertainty exist regarding best practices for managing complications; however, growing awareness has led to development of new guidelines to reduce risk and improve outcomes., Competing Interests: Disclosure Dr J.D. Pal has received research funding from Medtronic Inc and is a consultant for Medtronic Inc. Dr. Cornwell has received research funding from Medtronic Inc and is a consultant for Medtronic Inc. Mr C.N. Pierce is a consultant for Abbott. The other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

New Findings: LVAD patients are predisposed to hypertension which may increase the risk of stroke. Hypertension may result from markedly elevated levels of sympathetic nerve activity, which occurs through a baroreceptor-mediated pathway in response to chronic exposure to a non-physiologic (and reduced) pulse. Cerebral autoregulatory processes appear to be preserved in the absence of a physiologic pulse. Nevertheless, the rate of ischemic/embolic and hemorrhagic stroke is unacceptably high and is a major cause of morbidity and mortality in these patients. Despite normalization of a resting cardiac output, LVAD patients suffer from persistent, severe reductions in functional capacity., Abstract: Current generation left ventricular assist devices (LVADs) have led to significant improvements in survival compared to medical therapy alone, when used for management of patients with advanced heart failure. However, there are a number of side-effects associated with LVAD use, including hypertension, gastrointestinal bleeding, stroke, as well as persistent and severe limitations in functional capacity despite normalization of a resting cardiac output. These issues are, in large part, related to chronic exposure to a non-physiologic pulse, which contributes to a hyperadrenergic environment characterized by markedly elevated levels of sympathetic nerve activity through a baroreceptor-mediated pathway. In addition, these machines are unable to participate in, or contribute to, normal cardiovascular/autonomic reflexes that attempt to modulate flow through the body. Efforts to advance device technology and develop biologically sensitive devices may resolve these issues, and lead to further improvements in quality-of-life, functional capacity, and ultimately, survival, for the patients they support., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the topic of this review? Right heart dysfunction remains a major adverse event in patients with end stage heart failure undergoing left ventricular assist device placement. This article reviews the pathophysiology and clinical considerations of right heart failure in this patient population. What advances does it highlight? This review highlights the anatomic and physiological peculiarities of the interplay between left and right heart function in patients undergoing LVAD therapy. These would allow us to further advance our understanding of right ventricular function., Abstract: The adaptation of the right ventricular (RV) output to a left ventricular assist device (LVAD) often determines the fate of patients with pulmonary hypertension secondary to left heart failure. Pre-existing right heart dysfunction in patients with advanced left heart failure is the consequence of increased (arterial) afterload and not simply the consequence of myocardial disease. If unaccounted for, it has the potential of accelerating into clinical right heart failure after LVAD, leading to significant morbidity and mortality. After LVAD implantation, the RV has to face increased flow generated by the LVAD, cardiac arrhythmias and exaggerated functional interactions between both ventricles. Understanding the key physiological mechanisms of RV dysfunction in patients with end-stage heart failure will allow us to predict and therefore prevent RV failure after LVAD implantation., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

New Findings: What is the topic of this review? This review discusses how implantation of continuous flow left ventricular assist devices impact arterial stiffness and outcome. What advances does it highlight? Not all patients implanted with continuous flow left ventricular assist devices show an increase in arterial stiffness. However, in those patients where arterial stiffness increases, levels of composite outcome (stroke, gastrointestinal bleeding, pump thrombosis and death) is significantly higher than those who's arterial stiffness does not increase., Abstract: In parallel with the major advances in clinical care, technological advancements and implantation of mechanical circulatory support in patients with severe heart failure have resulted in these patients living longer. However, these patients are still at increased risk of stroke and gastrointestinal bleeding. The unique continuous flow produced by various left ventricular assist devices (LVADs) has been suggested as one potential reason for this increased risk of stroke and gastrointestinal bleeding. Furthermore, these continuous-flow (CF) devices challenge our understanding of circulatory blood pressure and flow regulation in relationship to organ health. In healthy pulsatile and dynamic systems, arterial stiffness is a major independent risk factor for stroke. However, to date, there are limited data regarding the impact of CF-LVAD therapy on arterial stiffness. The purpose of this report is to discuss the variable impact of CF-LVAD therapy on arterial stiffness and attempt to highlight some potential mechanisms linking these associations in this unique population., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

New Findings: What is the topic of this review? Patients with advanced heart failure who are implanted with left ventricular assist devices (LVADs) present an opportunity to understand the human circulation under extreme conditions. What advances does it highlight? LVAD patients have a unique circulation that is characterized by a reduced or even absent arterial pulse. The remarkable survival of these patients is accompanied by circulatory complications, including stroke, gastrointestinal bleeding and right-heart failure. Understanding the mechanisms related to the complications in LVAD patients will help the patients and also advance our fundamental understanding of the human circulation in general., Abstract: Some humans with chronic, advanced heart failure are surgically implanted with a left ventricular assist device (LVAD). Because the LVAD produces a continuous flow, a palpable pulse is often absent in these patients. This allows for a unique investigation of the human circulation and has created a controversy around the 'need' for a pulse. The medical debate has also generated a more generic, fundamental discussion into what is 'normal' arterial physiology and health. The comprehensive study and understanding of the arterial responses to drastically altered haemodynamics due to continuous-flow LVADs, at rest and during activity, presents an opportunity to significantly increase our current understanding of the fundamental components of arterial regulation (flow, blood pressure, sympathetic activity, endothelial function, pulsatility) in a way that could never have been studied previously. In a series of four articles, we summarize the talks presented at the symposium entitled 'Bionic women and men - Physiology lessons from implantable cardiac devices' presented at the 2019 Annual Meeting of The Physiological Society in Aberdeen, UK. The articles highlight the novel questions generated by physiological phenomena observed in LVAD patients and propose future areas of interest within the field of cardiovascular physiology., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

This study aimed to assess the efficacy of acute subanesthetic dosages of xenon inhalation to cause erythropoiesis and determine the effect of chronic xenon dosing on hematological parameters and athletic performance. To assess the acute effects, seven subjects breathed three subanesthetic concentrations of xenon: 30% fraction of inspired xenon (Fi Xe ) for 20 min, 50% Fi Xe for 5 min, and 70% Fi Xe for 2 min. Erythropoietin (EPO) was measured at baseline, during, and after xenon inhalation. To determine the chronic effects, eight subjects breathed 70% Fi Xe for 2 min on 7 consecutive days, and EPO, total blood, and plasma volume were measured. Phase II involved assessment of 12 subjects for EPO, total blood volume, maximal oxygen uptake, and 3-km time before and after random assignment to 4 wk of xenon or sham gas inhalation. Fi Xe 50% and 70% stimulated an increase in EPO at 6 h [+2.3 mIU/mL; 95% confidence interval (CI) 0.1-4.5; P = 0.038] and at 192 h postinhalation (+2.9 mIU/mL; 95% CI 0.6-5.1; P = 0.017), respectively. Seven consecutive days of dosing significantly elevated plasma volume (+491 mL; 95% CI 194-789; P = 0.002). Phase II showed no significant effect on EPO, hemoglobin mass, plasma volume, maximal oxygen uptake, or 3-km time. Acute exposure to subanesthetic doses of xenon caused a consistent increase in EPO, and 7 consecutive days of xenon inhalation significantly expanded plasma volume. However, this physiological response appeared to be transient, and 4 wk of xenon inhalation did not stimulate increases in plasma volume or erythropoiesis, leaving cardiorespiratory fitness and athletic performance unchanged. NEW & NOTEWORTHY This is the first study to examine each element of the cascade by which xenon inhalation is purported to take effect, starting with measurement of the hypoxia-inducible factor effector, erythropoietin, to hemoglobin mass and blood volume and athletic performance. We found that acute exposure to xenon increased serum erythropoietin concentration, although major markers of erythropoiesis remained unchanged. While daily dosing significantly expanded plasma volume, no physiological or performance benefits were apparent following 4 wk of dosing.

This study aimed to quantify the sedative effects, detection rates, and cardiovascular responses to xenon. On 3 occasions, participants breathed xenon (F i Xe 30% for 20 min; F i Xe 50% for 5 min; F i Xe 70% for 2 min) in a nonblinded design. Sedation was monitored by a board-certified anesthesiologist. During 70% xenon, participants were also verbally instructed to operate a manual value with time-to-task failure being recorded. Beat-by-beat hemodynamics were measured continuously by ECG, photoplethysmography, and transcranial Doppler. Over 48 h postadministration, xenon was measured in blood and urine by gas chromatography-mass spectrometry. Xenon caused variable levels of sedation and restlessness. Task failure of the self-operating value occurred at 60-90 s in most individuals. Over the first minute, 50% and 70% xenon caused a substantial reduction in total peripheral resistance ( P < 0.05). All dosages caused an increase in cardiac output ( P < 0.05). By the end of xenon inhalation, slight hypertension was observed after all three doses ( P < 0.05), with an increase in middle cerebral artery velocity ( P < 0.05). Xenon was consistently detected, albeit in trace amounts, up to 3 h after all three doses of xenon inhalation in blood and urine with variable results thereafter. Xenon inhalation caused sedation incompatible with self-operation of a breathing apparatus, thus causing a potential life-threatening condition in the absence of an anesthesiologist. Yet, xenon can only be reliably detected in blood and urine up to 3 h postacute dosing. NEW & NOTEWORTHY Breathing xenon in dosages conceivable for doping purposes (F i Xe 30% for 20 min; F i Xe 50% for 5 min; F i Xe 70% for 2 min) causes an initial rapid fall in total peripheral resistance with tachycardia and thereafter a mild hypertension with elevated middle cerebral artery velocity. These dose duration intervals cause sedation that is incompatible with operating a breathing apparatus and can only be detected in blood and urine samples with a high probability for up to ~3 h.

Bloodstream infections (BSIs) are common in patients with continuous-flow left ventricular assist devices (CF-LVADs). Whether CF-LVADs modulate the febrile response to BSIs is unknown. We retrospectively compared the febrile response to BSIs in patients with heart failure (HF) with CF-LVADs versus a control population of patients with HF receiving inotropic infusions. BSIs were adjudicated using the Centers for Disease Control and Prevention and the National Healthcare Safety Network criteria. Febrile status (temperature ≥38°C, 100.4 °F), temperature at presentation with BSI, and the highest temperature within 72 hours (Tmax) were collected. We observed 59 BSIs in LVAD patients and 45 BSIs in controls. LVAD patients were more likely to be afebrile and to have a lower temperature at presentation than control (88% vs 58%, p=0.002, and 37°C ±0.7 vs 37.7°C ±1.0, p=0.0009, respectively). By 72 hours, the difference in afebrile status diminished (53% vs 44%, p=0.42), and the Tmax was similar between the LVAD and control groups (37.9°C±0.9 vs 38.2°C±0.8, respectively, p=0.10). In conclusion, at presentation with a BSI, the vast majority of CF-LVAD patients were afebrile, an event which occurred at a higher frequency when compared with patients with advanced HF on chronic inotropes via an indwelling venous catheter. These data alert clinicians to have a very low threshold to obtain blood cultures in CF-LVAD patients even in the absence of fever. Further study is needed to determine whether a delayed or diminished febrile response represents another pathophysiological consequence of CF-LVADs., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Key Points: During long-term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension. Weightlessness prevents the normal cerebral volume and pressure 'unloading' associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology. By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments. Application of incremental LBNP demonstrated a non-linear dose-response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure. This non-invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension., Abstract: Patients with elevated intracranial pressure (ICP) exhibit neuro-ocular symptoms including headache, papilloedema and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space-flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: six ambulatory neurosurgical patients with parenchymal ICP-sensors and four former cancer patients with Ommaya-reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head-down tilt. LBNP from 0 to 50 mmHg at increments of 10 mmHg lowered ICP in a non-linear dose-dependent fashion; when supine (n = 10), ICP was decreased from 15 ± 2 mmHg to 14 ± 4, 12 ± 5, 11 ± 4, 10 ± 3 and 9 ± 4 mmHg, respectively (P < 0.0001). Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure at midbrain level minus ICP, was unchanged (from 70 ± 12 mmHg to 67 ± 9, 69 ± 10, 70 ± 12, 72 ± 13 and 74 ± 15 mmHg; P = 0.02). A 15° head-down tilt (n = 6) increased ICP to 26 ± 4 mmHg, while application of LBNP lowered ICP (to 21 ± 4, 20 ± 4, 18 ± 4, 17 ± 4 and 17 ± 4 mmHg; P < 0.0001) and increased CPP (P < 0.01). An LBNP of 20 mmHg may be the optimal level to lower ICP without impairing CPP to counteract spaceflight-associated neuro-ocular syndrome in astronauts. Furthermore, LBNP holds clinical potential as a safe, non-invasive method for lowering ICP and improving CPP for patients with pathologically elevated ICP on Earth., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Pulsatility seems to have a teleological role because evolutionary hierarchy favors higher ordered animals with more complex, multichamber circulatory systems that generate higher pulse pressure compared with lower ordered animals. Yet despite years of such natural selection, the modern generation of continuous-flow left ventricular assist devices (CF-LVADs) that have been increasingly used for the last decade have created a unique physiology characterized by a nonpulsatile, nonlaminar blood flow profile with the absence of the usual large elastic artery Windkessel effect during diastole. Although outcomes and durability have improved with CF-LVADs, patients supported with CF-LVADs have a high rate of complications that were not as frequently observed with older pulsatile devices, including gastrointestinal bleeding from arteriovenous malformations, pump thrombosis, and stroke. Given the apparent fundamental biological role of the pulse, the purpose of this review is to describe the normal physiology of ventricular-arterial coupling from pulsatile flow, the effects of heart failure on this physiology and the vasculature, and to examine the effects of nonpulsatile blood flow on the vascular system and potential role in complications seen with CF-LVAD therapy. Understanding these concomitant vascular changes with CF-LVADs may be a key step in improving patient outcomes as modulation of pulsatility and flow characteristics may serve as a novel, yet simple, therapy for reducing complications., (© 2018 American Heart Association, Inc.)

Objectives: The aim of this study was to measure aortic vascular stiffness from orthotopic heart transplant (OHT) patients exposed to varying types of flow as a result of the presence or absence of left ventricular assist device (LVAD) support pre-OHT., Background: The effects of continuous-flow LVADs (CF-LVADs) on vascular properties are unknown, but may contribute to the pathophysiology of CF-LVAD complications such as stroke, hypertension, and bleeding., Methods: Echocardiograms were reviewed from 172 OHT patients immediately before LVAD and at 3 time points post-OHT: baseline, 6 months, and 1 year. For each study, pulse pressure and aortic end-systolic and end-diastolic dimensions were used to calculate aortic strain, distensibility, and stiffness index. Patients were categorized into 3 groups based on the presence or absence of a LVAD and a pulse pre-OHT: No LVAD (n = 111), LVAD No Pulse (n = 30), and LVAD With Pulse (n = 31)., Results: The aortic stiffness index among LVAD No Pulse patients increased from 2.8 ± 1.1 pre-CF-LVAD to 10.9 ± 4.7 immediately post-OHT (p < 0.001). This aortic stiffness index was also significantly higher compared with No LVAD (3.4 ± 1.1; p < 0.001) and LVAD With Pulse (3.7 ± 1.4; p < 0.001) immediately post-OHT with attenuation of these differences by 1 year post-OHT. Similar findings were noted for the other indices of aortic stiffness., Conclusions: Aortic stiffness is markedly increased immediately post-OHT among patients bridged with CF-LVADs, with attenuation of this increased stiffness over the first year after transplant. These results suggest that aortic vascular properties are dynamic and may be influenced by alterations in flow pulsatility. As more patients are supported with CF-LVADs and as newer pump technology attempts to modulate pulsatility, further research examining the role of alterations in flow patterns on vascular function and the potential resultant systemic sequelae are needed., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the contributions of obesity and changes in body mass index (BMI) in mid-life to long-term heart failure (HF) risk independent of cardiorespiratory fitness (CRF) levels., Background: Obesity and low CRF are well-established risk factors for HF. However, given the inverse association between CRF and obesity, the independent contributions of BMI toward HF risk are not fully understood., Methods: We included 19,485 participants from the Cooper Center Longitudinal Study who survived to receive Medicare coverage, from 1999 to 2009. CRF was estimated in metabolic equivalents (METS) according to Balke treadmill time. Associations of BMI and BMI change with HF hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to the failure time data., Results: After 127,110 person-years of follow-up, we observed 1,038 HF hospitalization events. Higher mid-life BMI was significantly associated with greater risk of HF hospitalization after adjusting for established HF risk factors (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.12 to 1.26 per 3 kg/m 2 higher BMI). This association was attenuated after adjusting for CRF (HR: 1.10; 95% CI: 1.03 to 1.17 per 3 kg/m 2 higher BMI). CRF accounted for 47% of the HF risk associated with BMI. BMI change was not significantly associated with risk of HF in older age after adjustment for CRF change., Conclusions: Higher BMI-associated risk of HF is explained largely by differences in CRF levels. Furthermore, BMI change is not significantly associated with HF risk after adjusting for CRF changes. These findings highlight the importance of CRF in mediating BMI-associated HF risk., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

During heat stress, stroke volume is maintained in young adults despite reductions in cardiac filling pressures. This is achieved by a general augmentation of cardiac function, highlighted by a left and upward shift of the Frank-Starling relation. In contrast, healthy aged adults are unable to maintain stroke volume during heat stress. We hypothesized that this would be associated with a lack of shift in the Frank-Starling relation. Frank-Starling relations were examined in 11 aged [69 ± 4 (SD) yr, 4 men/7 women] and 12 young (26 ± 5 yr, 6 men/6 women) adults during normothermic and heat stress (1.5°C increase in core temperature) conditions. During heat stress, increases in cardiac output were attenuated in aged adults (+2.5 ± 0.3 (95% CI) vs. young: +4.5 ± 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30 ± 4 vs. young: +42 ± 5 beats/min, P < 0.01). In contrast to our hypothesis, a leftward shift of the Frank-Starling relation maintained stroke volume during heat stress in aged adults (76 ± 8 vs. normothermic: 74 ± 8 ml, P = 0.38) despite reductions in cardiac filling pressure (6.6 ± 1.0 vs. normothermic: 8.9 ± 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to return cardiac filling pressure during heat stress to normothermic values, which resulted in a greater stroke volume for a given cardiac filling pressure in both groups. These results demonstrate that the Frank-Starling relation shifts during heat stress in healthy young and aged adults, thereby preserving stroke volume despite reductions in cardiac filling pressures., (Copyright © 2016 the American Physiological Society.)

Background: Current-generation left ventricular assist devices provide circulatory support that is minimally or entirely nonpulsatile and are associated with marked increases in muscle sympathetic nerve activity (MSNA), likely through a baroreceptor-mediated pathway. We sought to determine whether the restoration of pulsatile flow through modulations in pump speed would reduce MSNA through the arterial baroreceptor reflex., Methods and Results: Ten men and 3 women (54 ± 14 years) with Heartmate II continuous-flow left ventricular assist devices underwent hemodynamic and sympathetic neural assessment. Beat-to-beat blood pressure, carotid ultrasonography at the level of the arterial baroreceptors, and MSNA via microneurography were continuously recorded to determine steady-state responses to step changes (200-400 revolutions per minute) in continuous-flow left ventricular assist device pump speed from a maximum of 10,480 ± 315 revolutions per minute to a minimum of 8500 ± 380 revolutions per minute. Reductions in pump speed led to increases in pulse pressure (high versus low speed: 17 ± 7 versus 26 ± 12 mm Hg; P<0.01), distension of the carotid artery, and carotid arterial wall tension (P<0.05 for all measures). In addition, MSNA was reduced (high versus low speed: 41 ± 15 versus 33 ± 16 bursts per minute; P<0.01) despite a reduction in mean arterial pressure and was inversely related to pulse pressure (P=0.037)., Conclusions: Among subjects with continuous-flow left ventricular assist devices, the restoration of pulsatile flow through modulations in pump speed leads to increased distortion of the arterial baroreceptors with a subsequent decline in MSNA. Additional study is needed to determine whether reduction of MSNA in this setting leads to improved outcomes., (© 2015 American Heart Association, Inc.)

Background: Insertion of a left ventricular assist device (LVAD) is an accepted therapy for advanced heart failure patients. However, the effects on end-organ perfusion, including cerebral autoregulation, are unclear in the presence of reduced pulsatility. Therefore, the objective of this study was to determine whether cerebral autoregulation is impaired in patients with continuous-flow (CF) LVADs., Methods: Dynamic cerebral autoregulation was assessed in both time-domain (autoregulatory index) and frequency-domain (transfer function analysis) analyses in 9 CF-LVAD subjects, 5 pulsatile LVAD subjects and 10 healthy controls, by evaluating mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) during a sit-stand maneuver at 0.05 Hz (10-second sit, 10-second stand). The autoregulatory index was calculated as the percent change in mean CBFV per mm Hg change in MAP., Results: The magnitude of oscillation in MAP and CBFV was greater in subjects with pulsatile LVADs than either CF-LVADs or healthy controls (p = 0.065 for MAP, p = 0.004 for CBFV). The autoregulatory index and transfer function gain were similar among groups, indicating that dynamic cerebral autoregulation is preserved among patients with CF-LVADs., Conclusions: Cerebral blood flow in patients with CF-LVADs is comparable to that of healthy controls across a range of blood pressures. Patients with pulsatile devices have greater oscillations in MAP and CBFV. However, dynamic cerebral autoregulation is preserved among subjects with either type of device. Thus, the reduction in pulsatility afforded by CF-LVADs does not impair normal autoregulatory processes., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)