Search

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.

Background A negative impact of premature birth on health in adulthood is well established. However, it is not clear whether healthy adults who were born prematurely but have similar physical activity levels compared to adults born at term have a reduced maximal aerobic exercise capacity (maximum oxygen consumption [VO2max]). Objective We aimed to determine the effect of premature birth on aerobic exercise capacity and lung function in otherwise healthy, physically active individuals. Methods A broad literature search was conducted in the PubMed database. Search terms included ‘preterm/premature birth’ and ‘aerobic exercise capacity’. Maximal oxygen consumption (mL/kg/min) was the main variable required for inclusion, and amongst those investigations forced expiratory volume in 1 s (FEV1, % predicted) was evaluated as a secondary parameter. For the systematic review, 29 eligible articles were identified. Importantly, for the meta-analysis, only studies which reported similar activity levels between healthy controls and the preterm group/s were included, resulting in 11 articles for the VO2max analysis (total n = 688, n = 333 preterm and n = 355 controls) and six articles for the FEV1 analysis (total n = 296, n = 147 preterm and n = 149 controls). Data were analysed using Review Manager ( Review Manager. RevMan version 5.4 software. The Cochrane Collaboration; 2020.). Results The systematic review highlighted the broad biological impact of premature birth. While the current literature tends to suggest that there may be a negative impact of premature birth on both VO2max and FEV1, several studies did not control for the potential influence of differing physical activity levels between study groups, thus justifying a focused meta-analysis of selected studies. Our meta-analysis strongly suggests that prematurely born humans who are otherwise healthy do have a reduced VO2max (mean difference: − 4.40 [95% confidence interval − 6.02, − 2.78] mL/kg/min, p Z = 5.32) and FEV1 (mean difference − 9.22 [95% confidence interval − 13.54, − 4.89] % predicted, p Z = 4.18) independent of physical activity levels. Conclusions Whilst the current literature contains mixed findings on the effects of premature birth on VO2max and FEV1, our focused meta-analysis suggests that even when physical activity levels are similar, there is a clear reduction in VO2max and FEV1 in adults born prematurely. Therefore, future studies should carefully investigate the underlying determinants of the reduced VO2max and FEV1 in humans born preterm, and develop strategies to improve their maximal aerobic capacity and lung function beyond physical activity interventions.

Limited data exist on the circadian blood pressure (BP) and heart rate (HR) variations that occur in heart failure (HF) patients on left ventricular assist device (LVAD) support.We prospectively recorded clinic and 24-hour ambulatory BP and HR data in patients on HeartMate II LVAD support. Results were compared to HF patients with ejection fraction ≤30% and controls with no history of cardiovascular disease. Physiologic nocturnal BP and HR dipping was defined as a ≥10% decline compared to daytime values.Twenty-nine LVAD patients (age 59 ± 15 years, 76% male, 38% ischemic etiology), 25 HF patients (age 64 ± 13 years, 84% male, 32% ischemic etiology) and 26 controls (age 56 ± 9 years, 62% male) were studied. Normal nocturnal BP dipping was less frequent in LVAD patients (10%) than in HF patients (28%) and controls (62%) and reversed BP dipping (BP increase at night) was more common in LVAD patients (24%), compared to HF (16%) and controls (8%), (p0.001, for all comparisons). Physiologic HR reduction was less frequent in LVAD patients (14%), compared to HF (16%) and controls (59%) (p0.001, for all comparisons). Among LVAD patients, 36% exhibited sustained hypertension over the 24-hours and 25% had white-coat hypertension.Treatment of advanced HF with an LVAD does not restore physiologic circadian variability of BP and HR; additionally, BP was not adequately controlled in more than a third of LVAD patients, and a quarter of them exhibited white-coat hypertension. Future studies are warranted to confirm these findings and investigate prognostic and management implications in this population.

During pregnancy, assessment of cardiac output (𝑄̇), a fundamental measure of cardiovascular function, provides important insight into maternal adaptation. However, methods for dynamic 𝑄̇ measurement require validation. The purpose of this study was to estimate the agreement of 𝑄̇ measured by echocardiography and Modelflow® at rest and during submaximal exercise in non-pregnant (n = 18), pregnant (n = 15, 22-26 weeks gestation) and postpartum women (n = 12, 12-16 weeks post-delivery). Simultaneous measurements of 𝑄̇ derived from echocardiography [criterion] and Modelflow® were obtained at rest and during low-moderate intensity (25% and 50% peak power output) cycling exercise and compared using Bland-Altman analysis and limits of agreement. Agreement between echocardiography and Modelflow® was poor in non-pregnant, pregnant and postpartum women at rest (mean difference ± SD: -1.1 ± 3.4; -1.2 ± 2.9; -1.9 ± 3.2 L.min-1), and this remained evident during exercise. The Modelflow® method is not recommended for 𝑄̇ determination in research involving young, healthy non-pregnant and pregnant women at rest or during dynamic challenge. Previously published 𝑄̇ data from studies utilising this method should be interpreted with caution.

While rates of stroke have declined with the HeartMate3 (HM3) continuous- flow (CF) left ventricular assist device (LVAD), the impact of non-pulsatile flow and artificial pulse physiology on cerebrovascular function is not known. We hypothesized that improved hemodynamics and artificial pulse physiology of HM3 patients would augment cerebrovascular metabolic reactivity (CVR) compared with HeartMate II (HMII) CF-LVAD and heart failure (HF) patients.Mean, peak systolic and diastolic flow velocities (MFV, PSV, MinFV, respectively) and cerebral pulsatility index were determined in the middle cerebral artery (MCA) before and after a 30 sec breath-hold challenge in 90 participants: 24 healthy controls; 30 HF, 15 HMII, and 21 HM3 patients.In HM3 patients, breath-holding increased MFV (Δ8 ± 10 cm/sec, p.0001 vs baseline) to levels similar to HF patients (Δ9 ± 8 cm/sec, p.05), higher than HMII patients (Δ2 ± 8 cm/sec, p.01) but lower than healthy controls (Δ13 ± 7 cm/sec, p.05). CF-LVAD altered the proportion of systolic and diastolic flow responses as reflected by a differential cerebral pulsatility index (p = .03). Baseline MFV was not related to CVR (rCompared with HMII, HM3 patients have a significantly improved CVR. However, CVR remains lower in HM3 and HF patients than in healthy controls, therefore suggesting that changes in cerebral hemodynamics are not reversed by CF-LVAD therapy. Further research on the mechanisms and the long-term impact of altered cerebral hemodynamics in this unique patient population are warranted.

In the general population, increased aortic stiffness is associated with an increased risk of cardiovascular events. Previous studies have demonstrated an increase in aortic stiffness in patients with a continuous flow left ventricular assist device (CF-LVAD). However, the association between aortic stiffness and common adverse events is unknown.Forty patients with a HeartMate II (HMII) (51 $ 11 years; 20% female; 25% ischemic) implanted between January 2011 and September 2017 were included. Two-dimensional transthoracic echocardiograms of the ascending aorta, obtained before HMII placement and early after heart transplant, were analyzed to calculate the aortic stiffness index (AO-SI). The study cohort was divided into patients who had an increased vs decreased AO-SI after LVAD support. A composite outcome of gastrointestinal bleeding, stroke, and pump thrombosis was defined as the primary end point and compared between the groups. While median AO-SI increased significantly after HMII support (AO-SI 4.4-6.5, P = .012), 16 patients had a lower AO-SI. Patients with increased (n = 24) AO-SI had a significantly higher rate of the composite end point (58% vs 12%, odds ratio 9.8, P.01). Similarly, those with increased AO-SI tended to be on LVAD support for a longer duration, had higher LVAD speed and reduced use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.Increased aortic stiffness in patients with a HMII is associated with a significantly higher rates of adverse events. Further studies are warranted to determine the causality between aortic stiffness and adverse events, as well as the effect of neurohormonal modulation on the conduit vasculature in patients with a CF-LVAD.

Left ventricular assist devices (LVADs) are associated with major vascular complications including stroke and gastrointestinal bleeding (GIB). These adverse vascular events may be the result of widespread vascular dysfunction resulting from pre-LVAD abnormalities or continuous flow during LVAD therapy. We hypothesized that pre-existing large artery atherosclerosis and/or abnormal blood flow as measured in carotid arteries using ultrasonography are associated with a post-implantation composite adverse outcome including stroke, GIB, or death. We retrospectively studied 141 adult HeartMate II patients who had carotid ultrasound duplex exams performed before and/or after LVAD surgery. Structural parameters examined included plaque burden and stenosis. Hemodynamic parameters included peak-systolic, end-diastolic, and mean velocity as well as pulsatility index. We examined the association of these measures with the composite outcome as well as individual subcomponents such as stroke. After adjusting for established risk factors, the composite adverse outcome was associated with pre-operative moderate-to-severe carotid plaque (OR 5.08, 95% CI 1.67-15.52) as well as pre-operative internal carotid artery stenosis (OR 9.02, 95% CI 1.06-76.56). In contrast, altered hemodynamics during LVAD support were not associated with the composite outcome. Our findings suggest that pre-existing atherosclerosis possibly in combination with LVAD hemodynamics may be an important contributor to adverse vascular events during mechanical support. This encourages greater awareness of carotid morphology pre-operatively and further study of the interaction between hemodynamics, pulsatility, and structural arterial disease during LVAD support.

Postmenopausal women have lower resting cardiac function than premenopausal women, but whether the menopause influences maximal cardiac output and hence exercise capacity is unclear. It is possible that premenopausal and postmenopausal women achieve similar improvements in maximal aerobic capacity (V˙O2max) and cardiac output with exercise training via different regional left ventricular muscle function ("LV mechanics"), as suggested by in vitro and animal studies. The aim of this study was to investigate the effects of the menopause on LV mechanics and adaptations to exercise training.Twenty-five healthy untrained middle-age women (age, 45-58 yr; 11 premenopausal, 14 postmenopausal) completed 12 wk of exercise training. Before and after exercise training, (i) V˙O2max and blood volume were determined, and (ii) LV mechanics were assessed using echocardiography at rest and during two submaximal physiological tests - lower-body negative pressure and supine cycling.The increase in V˙O2max after exercise training was 9% smaller in postmenopausal than premenopausal women, concomitant with a smaller increase in blood volume (P0.05). However, cardiac output and LV volumes were not different between premenopausal and postmenopausal women (P0.05) despite altered regional LV muscle function, as indicated by higher basal mechanics in premenopausal women during the physiological tests after exercise training (P0.05).These findings are the first to confirm altered LV mechanics in postmenopausal women. In addition, the reduced aerobic adaptability to exercise training in postmenopausal women does not appear to be a central cardiac limitation and may be due to altered blood volume distribution and lower peripheral adaptations.

Cardiac output during exercise increases by as much as fivefold in the untrained man, and by as much as eightfold in the elite athlete. Increasing venous return is a critical but much overlooked component of the physiological response to exercise. Cardiac disorders such as constrictive pericarditis, restrictive cardiomyopathy and pulmonary hypertension are recognised to impair preload and cause exercise limitation; however, the effects of peripheral venous obstruction on cardiac function have not been well described. This manuscript will discuss how obstruction of the iliocaval venous outflow can lead to impairment in exercise tolerance, how such obstructions may be diagnosed, the potential implications of chronic obstructions on sympathetic nervous system activation, and relevance of venous compression syndromes in heart failure with preserved ejection fraction.

Dependent on timing of assessment, anesthetic agents and specifically medetomidine negatively affect cardiac function in great apes. The aim of this study was to determine the influence of tiletamine–zolazepam (TZ) with and without medetomidine on cardiac structure and function in healthy chimpanzees (Pan troglodytes) during a period of relative blood pressure stability. Twenty-four chimpanzees living in an African wildlife sanctuary undergoing routine health assessments were stratified by age, sex, and body mass and randomized to be anesthetized using either TZ (6 mg/kg; n = 13; seven males and six females) or a combination of TZ (2 mg/kg) and medetomidine (TZM; 0.02 mg/kg; n = 11; five males and six females). During health checks, regular heart rate and blood pressure readings were taken and a standardized echocardiogram was performed 20–30 min after induction. Data were compared between the two anesthetic groups using independent-samples t or Mann–Whitney U tests. Although heart rate (mean ± SD; TZ: 76 ± 10 bpm; TZM: 65 ± 14 bpm, P = 0.027), cardiac output (TZ: 3.0 ± 0.7 L/min; TZM: 2.4 ± 0.7 L/min, P = 0.032), and mitral A-wave velocities (TZ: 0.51 ± 0.16 cm/s; TZM: 0.36 ± 0.10 cm/s, P = 0.013) were lower in the TZM group, there were no statistically significant differences in cardiac structure or the remaining functional variables between groups. Furthermore, there were no statistical differences in systolic (TZ 114.6 ± 14.9 mmHg; TZM: 123.0 ± 28.1 mmHg; P = 0.289) or diastolic blood pressure (TZ: 81.8 ± 22.3 mmHg, TZM: 83.8 ± 20.1 mmHg; P = 0.827) between the groups during the echocardiogram. This study has shown that during a period of relative blood pressure stability, during the first 20–30 min after induction there are few differences in measures of cardiac structure and function between protocols using TZ with or without medetomidine in healthy chimpanzees.

Objective To evaluate left ventricular (LV) mechanics in the second trimester of healthy pregnancy and to determine the influence of underpinning hemodynamics (heart rate (HR), preload and afterload) on LV mechanics during gestation. Methods This was a cross-sectional study of 18 non-pregnant, 14 nulliparous pregnant (22-26 weeks' gestation) and 13 primiparous postpartum (12-16 weeks after delivery) women. All pregnant and postpartum women had uncomplicated, singleton gestations. Cardiac structure and function were assessed using echocardiography. LV mechanics, specifically longitudinal strain, circumferential strain and twist/untwist, were measured using speckle-tracking echocardiography. Differences between groups were identified using ANCOVA, with age, HR, end-diastolic volume (EDV) and systolic blood pressure (SBP) as covariates. Relationships between LV mechanics and hemodynamics were examined using Pearson's correlation. Results There were no significant differences in LV structure and traditional measurements of systolic and diastolic function between the three groups. Pregnant women, compared with non-pregnant ones, had significantly higher resting longitudinal strain (-22 ± 2% vs -17 ± 3%; P = 0.002) and basal circumferential strain (-23 ± 4% vs -16 ± 2%; P = 0.001). Apical circumferential strain and LV twist and untwist mechanics were similar between the three groups. No statistically significant relationships were observed between LV mechanics and HR, EDV or SBP within the groups. Conclusions Compared to the non-pregnant state, pregnant women in the second trimester of a healthy pregnancy have significantly greater resting systolic function, as assessed by LV longitudinal and circumferential strain. Contrary to previous work, these data show that healthy pregnant women should not exhibit reductions in resting systolic function between 22 and 26 weeks' gestation. The enhanced myocardial contractile function during gestation does not appear to be related to hemodynamic load and could be the result of other physiological adaptations to pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Previous longitudinal studies suggest that left ventricular (LV) structure is unaltered with resistance exercise training (RT) in young men. However, evidence from aerobic exercise training suggests that early changes in functional LV wall mechanics may occur prior to and independently of changes in LV size, although short-term changes in LV mechanics and structural remodelling in response to RT protocols have not been reported. Therefore, the purpose of this study was to examine the effects of RT on LV mechanics in healthy men performing 2 different time-under-tension protocols. Forty recreationally trained men (age: 23 ± 3 years) were randomized into 12 weeks of whole-body higher-repetition RT (20–25 repetitions/set to failure at ∼30%–50% 1 repetition maximum (1RM); n = 13), lower-repetition RT (8–12 repetitions/set to failure at ∼75%–90% 1RM; n = 13), or an active control period (n = 14). Speckle tracking echocardiography was performed at baseline and following the intervention period. Neither RT program altered standard measures of LV volumes (end-diastolic volume, end-systolic volume, or ejection fraction; P > 0.05) or indices of LV mechanics (total LV twist, untwisting rate, twist-to-shortening ratio, untwisting-to-twist ratio, or longitudinal strain; P > 0.05). This is the first longitudinal study to assess both LV size and mechanics after RT in healthy men, suggesting a maintenance of LV size and twist mechanics despite peripheral muscle adaptations to the training programs. These results provide no evidence for adverse LV structural or functional remodelling in response to RT in young men and support the positive role of RT in the maintenance of optimal cardiovascular function, even with strenuous RT.

Purpose The increased physiological demand of pregnancy results in the profound adaptation of the maternal cardiovascular system, reflected by greater resting cardiac output and left ventricular (LV) deformation. Whether the increased resting demand alters acute cardiac responses to exercise in healthy pregnant women is not well understood. Methods Healthy nonpregnant (n = 18), pregnant (n = 14, 22-26 wk gestation), and postpartum women (n = 13, 12-16 wk postdelivery) underwent assessments of cardiac function and LV mechanics at rest, during a sustained isometric forearm contraction (30% maximum), and during low-intensity (LOW) and moderate-intensity (MOD) dynamic cycling exercise (25% and 50% peak power output). Significant differences (α = 0.05) were determined using ANCOVA and general linear model (resting value included as covariate). Results When accounting for higher resting cardiac output in pregnant women, pregnant women had greater cardiac output during isometric contraction (2.0 ± 0.3 L·min-1·m-1.83; nonpregnant, 1.3 ± 0.2 L·min-1·m-1.83; postpartum, 1.5 ± 0.5 L·min-1·m-1.83; P = 0.02) but similar values during dynamic cycling exercise (pregnant, LOW = 2.8 ± 0.4 L·min-1·m-1.83, MOD = 3.4 ± 0.7 L·min-1·m-1.83; nonpregnant, LOW = 2.4 ± 0.3 L·min-1·m-1.83, MOD = 3.0 ± 0.3 L·min-1·m-1.83; postpartum, LOW = 2.3 ± 0.4 L·min-1·m-1.83, MOD = 3.0 ± 0.5 L·min-1·m-1.83; P = 0.96). Basal circumferential strain was higher in pregnant women at rest, during the sustained isometric forearm contraction (-23.5% ± 1.2%; nonpregnant, -14.6% ± 1.4%; P = 0.001), and during dynamic cycling exercise (LOW = -27.0% ± 4.9%, MOD = -27.4% ± 4.6%; nonpregnant, LOW = -15.8% ± 4.5%, MOD = -15.2% ± 6.7%; P = 0.012); however, other parameters of LV mechanics were not different between groups. Conclusion The results support that the maternal heart can appropriately respond to additional cardiac demand and altered loading experienced during acute isometric and dynamic exercise, although subtle differences in responses to these challenges were observed. In addition, the LV mechanics that underpin global cardiac function are greater in pregnant women during exercise, leading to the speculation that the hormonal milieu of pregnancy influences regional deformation.

The human heart is an asymmetrical structure that consists of oblique, circumferential, and transmural fibers, as well as laminae and sheets. Sequential electrical activation of all the muscle fibers ultimately results in a coordinated contraction of the heart muscle also referred to as “deformation.” This is immediately followed by myocardial relaxation, when the preceding deformation is reversed, and the ventricles fill with blood. Given the complexity of these repetitive motions, it is not surprising that there is great diversity in the myocardial deformation between different individuals and between distinct populations. Exercise presents a natural challenge to determine the full capacity of an individual’s heart, and modern imaging technologies allow for the non-invasive assessment of myocardial deformation during exercise. In this chapter, the most relevant anatomical basis for myocardial deformation is summarized and definitions of the most relevant parameters are provided. Then, the general cardiac responses to exercise are highlighted before the current knowledge on myocardial deformation during exercise is discussed. The literature clearly indicates that the echocardiographic evaluation of myocardial deformation during exercise holds great promise for the identification of sub-clinical disease. Future studies should aim to determine the mechanisms of differential expression of myocardial deformation during exercise in health and disease.

Introduction: The assessment of middle cerebral artery (MCA) haemodynamics is essential for the diagnosis and monitoring of cerebrovascular disease. However, conventional transcranial Doppler (TCD) may not capture the correct flow velocities because of sub-optimal angles of insonation. Conversely, 2-D ultrasound (2D-US) allows for the visualisation and angle-correction of MCA haemodynamics. Therefore, this study aimed to determine potential differences in MCA haemodynamics obtained with TCD and 2D-US. Methods: MCA haemodynamics were obtained in a blinded, randomised order with TCD and 2D-US (non-angle-corrected = 2D-US-NON and angle-corrected = 2D-US-ANGLE) from the temporal left posterior window in twenty-seven healthy participants. Recordings were analysed for peak-systolic velocity (PSV), end-diastolic velocity (ED), pulsatility index (PI) and resistance index (RI). Statistical agreements between TCD and 2D-US were determined using linear regression, independent samples t-test and Bland-Altman analysis. Results: MCA haemodynamics obtained with TCD explained less than 50% of the values obtained with 2D-US-NON & 2D-US-ANGLE, respectively (PSV r2 = 0.34 & 0.37; ED: r2 = 0.37 & 0.44; PI: r2 = 0.20 & 0.22; RI: r2 = 0.30 & 0.32). Compared with 2D-US-NON, TCD produced similar PSV (p = 0.65) but significantly higher ED (p < 0.0001), lower PI (p < 0.0001) and lower RI (p < 0.0001). 2D-US angle-correction resulted in a significantly higher PSV compared with TCD (p = 0.005) while all other differences remained. Bland-Altman analysis revealed a bias between the two methods ranging from 11–40%, with large individual variability. Conclusion: TCD and 2D ultrasound produce significantly different values for MCA haemodynamics, even when 2D-US is non-angle-corrected. This may have important implications when using indices of MCA haemodynamics in the evaluation of cerebrovascular disease.

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.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.

Article published in The Journal of Physiology, available at https://doi.org/10.1113/JP276729

What is the central question of this study? What is the role of heart muscle function in the increased output of remodelled, larger hearts? What is the main finding and its importance? The greater stroke volume of endurance athletes is not associated with enhanced function of the heart muscle (i.e. left ventricular twist, torsion and twist-to-shortening) in normal and low-oxygen environments. These data indicate that, in the process of cardiac adaptation, left ventricular twist may play an important role that is not related to generating a larger output. Since enlarged hearts with low output can develop in disease, the present findings may influence the future interpretation of heart muscle function in patients.Despite increased stroke volume (SV), 'athlete's heart' has been proposed to have a similar left ventricular (LV) muscle function - as represented by LV twist - compared with the untrained state. However, the underpinning mechanisms and the associations between SV/cardiac output and LV twist during exercise are unknown. We hypothesised that endurance athletes would have a significantly lower twist-to-shortening ratio (TwSR, a parameter that relates twist to the shortening of heart muscle layers) at rest, but significantly greater LV muscle function during exercise. Eleven endurance trained male runners and 13 untrained males were tested at rest and during supine cycling exercise in normoxia and hypoxia (increased cardiac output but unaltered SV). Despite the expected cardiac remodelling in endurance athletes, LV twist, torsion, TwSR, strain and strain rate ('LV systolic mechanics') did not differ significantly between groups (P 0.05). Structural remodelling, as per relative wall thickness, and LV twist did not correlate (r

Carotid artery longitudinal wall motion (CALM) has recently attracted interest as an indicator of arterial health; however, the regulation of CALM is poorly understood. We conducted a series of studies aimed at manipulating pulse pressure (PP), left ventricular (LV) motion, and carotid shear rate, which have been previously suggested to regulate various components of CALM pattern and magnitude. To determine the regulatory influences on CALM, fifteen healthy males (22 ± 2 years) were exposed to three acute interventions: the Serial Subtraction Test (SST), the Cold Pressor Test (CPT), and exposure to sublingual nitroglycerine (NTG). The SST elicited increases in PP (P 0.05). Similarly, the CPT elicited increases in PP (P = 0.01), basal LV rotation (P = 0.04) and carotid shear rate (P = 0.01), with no changes in CALM (P > 0.05). Conversely, exposure to NTG elicited no change in PP (P = 0.22), basal (P = 0.65) or apical LV rotation (P = 0.45), but did decrease carotid shear rate (P 0.05). Considerable individual variability in CALM responses prompted further analyses where all three interventions were pooled for change scores. Changes in LV basal rotation were related to changes systolic retrograde CALM (B = −0.025, P = 0.03), while changes in carotid shear rate were related to changes in diastolic CALM displacement (B = 0.0009, P = 0.01). The interventions were underpinned by relationships between CALM and both LV basal rotation and local shear rate at the individual level, indicating that cardiac and hemodynamic factors may influence CALM in humans. This article is protected by copyright. All rights reserved

Background Preclinical studies have reported that a single treadmill session performed 24 h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24 h prior to treatment changes this response. Methods Breast cancer patients were randomized to either 30 min of vigorous-intensity exercise 24 h prior to the first doxorubicin treatment (n = 13), or no vigorous exercise for 72 h prior to treatment (control, n = 11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24–48 h after the treatment. Results Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p ≤ 0.01). Whereas systemic vascular resistance (p < 0.01) decreased, and ejection fraction (p = 0.02) and systolic strain rate (p < 0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p < 0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure. Conclusion The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24 h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin. Background Preclinical studies have reported that a single treadmill session performed 24 h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24 h prior to treatment changes this response. Methods Breast cancer patients were randomized to either 30 min of vigorous-intensity exercise 24 h prior to the first doxorubicin treatment (n = 13), or no vigorous exercise for 72 h prior to treatment (control, n = 11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24–48 h after the treatment. Results Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p ≤ 0.01). Whereas systemic vascular resistance (p < 0.01) decreased, and ejection fraction (p = 0.02) and systolic strain rate (p < 0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p < 0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure. Conclusion The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24 h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin.

Cardiovascular function generally decreases with age, but whether this decrease differs between men and women is unclear. Our aims were twofold: (1) to investigate age-related sex differences in left ventricular (LV) structure, function and mechanics, and (2) to compare these measures between pre- and postmenopausal women in the middle-aged group.Resting echocardiography was performed in a cross-sectional sample of 82 healthy adults (14 young men, 19 middle-aged men, 15 young women, 34 middle-aged women: 15 premenopausal and 19 postmenopausal). Two-way ANOVAs were used to examine sex × age interactions, and t-tests to compare pre- and postmenopausal women (α 0.1).Normalized LV mass, stroke volume and end-diastolic volume were significantly lower in middle-aged than young men, but this difference was smaller between middle-aged and young women. Peak systolic apical mechanics were significantly greater in middle-aged men than in middle-aged women, but not between young men and women. Postmenopausal women had significantly lower LV relaxation and mechanics (torsion, twisting velocity and apical circumferential strain rates) compared with middle-aged premenopausal women.Our cross-sectional findings suggest that the hearts of men and women may age differently, with men displaying greater differences in LV volumes accompanied by differences in apical mechanics.

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.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.

Cardiac output (CO), along with blood pressure and vascular resistance, is one of the most important parameters of maternal hemodynamic function. Substantial changes in CO occur in normal pregnancy and in most obstetric complications. With the development of several non-invasive techniques for the measurement of CO, there is a growing interest in the determination of this parameter in pregnancy. These techniques were initially developed for use in critical-care settings and were subsequently adopted in obstetrics, often without appropriate validation for use in pregnancy. In this article, methods and devices for the measurement of CO are described and compared, and recommendations are formulated for their use in pregnancy, with the aim of standardizing the assessment of CO and peripheral vascular resistance in clinical practice and research studies on maternal hemodynamics. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Regular participation in exercise has long been known to result in cardiovascular adaptation. Historically, the ‘athlete’s heart’ hypothesis has encouraged a dichotomised view of the heart’s adaptation to sport, depending on whether the physical activity was either of isotonic activity (runners and swimmers) resulting in ‘cardiomegaly’ or of isometric effort (wrestlers and shot putters, ie, ‘strength’ athletes) with clear peripheral adaptations and an ‘obvious increase in cardiac size’.1 Today, the classification of sports according to their physiological demands acknowledges a greater diversity of exposure, depending on the physical activity, with an emphasis on a ‘graded transition’ between the main categories: dynamic, static and impact.2 Still, our understanding of the determinants of structural and functional cardiovascular adaptation to exercise are limited, and the consequences for health remain a matter of debate.3 In their Heart paper, Hedman et al 4 add to the current knowledge beyond the athlete’s heart by presenting data on blood pressure from a large cohort of young athletes. The authors aimed at investigating blood pressure in preparticipation screening, and to evaluate the role of blood pressure against left ventricular (LV) remodelling. Participants’ systolic and diastolic blood pressure was classified according to US and European hypertension guidelines. They observed that one-third of athletes presented with blood pressure exceeding systolic and/or diastolic thresholds of the current US guidelines. Furthermore, systolic blood pressure was associated with LV remodelling and altered diastolic cardiac function, but not systolic function. The findings contribute to our understanding of exercise-induced cardiovascular adaptation, and several …

Elevated blood pressure (BP) has been linked to adverse events during left ventricular assist device support. In this study we investigated the association between outpatient BP and stroke or suspected pump thrombosis among HeartMate II (HMII) recipients.We retrospectively studied 220 HMII patients. Serial outpatient BP measurements were averaged. Patients were categorized by: (1) mean arterial pressure (MAP), high (90 mm Hg) vs intermediate (80 mm Hg ≤ MAP ≤ 90 mm Hg) vs low (80 mm Hg); (2) systolic BP (SBP), high (≥101 mm Hg, median) vs low; and (3) pulse pressure (PP), high (≥22 mm Hg, median) vs low. To assess visit-to-visit BP variability, patients were divided in quartiles of standard deviation of MAP and SBP. The primary end-point was the composite of stroke or suspected pump thrombosis.The risk for the primary end-point was increased in the high MAP group (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.49 to 5.05, vs intermediate MAP; and 6.73, 1.9 to 23.9, vs low MAP). MAP had higher predictive value for the primary end-point compared with SBP (p = 0.05). Patients with high SBP had a higher rate of stroke (HR 2.8, 95% CI 1.09 to 7.17, vs low SBP). The combination of high SBP and low PP was associated with the highest risk for stroke. The lowest quartile of visit-to-visit MAP variability was associated with the highest risk for the primary end-point.Elevated outpatient BP is associated with increased risk for stroke or suspected pump thrombosis in HMII recipients. Reduced PP and low visit-to-visit BP variability may confer additional risk.

The anatomy of the adult human left ventricle (LV) is the result of its complex interaction with its environment. From the fetal to the neonatal to the adult form, the human LV undergoes an anatomical transformation that finally results in the most complex of the four cardiac chambers. In its adult form, the human LV consists of two muscular helixes that surround the midventricular circumferential layer of muscle fibers. Contraction of these endocardial and epicardial helixes results in a twisting motion that is thought to minimize the transmural stress of the LV muscle. In the healthy myocardium, the LV twist response to stimuli that alter preload, afterload, or contractility has been described and is deemed relatively consistent and predictable. Conversely, the LV twist response in patient populations appears to be a little more variable and less predictable, yet it has revealed important insight into the effect of cardiovascular disease on LV mechanical function. This review discusses important methodological aspects of assessing LV twist and evaluates the LV twist responses to the main physiological and pathophysiological states. It is concluded that correct assessment of LV twist mechanics holds significant potential to advance our understanding of LV function in human health and cardiovascular disease.

NEW FINDINGS: What is the central question of this study? Left ventricular (LV) twist is reduced when afterload is increased, but the meaning of this specific heart muscle response and its impact on cardiac output are not well understood. What is the main finding and its importance? This study shows that LV twist responds even when arterial haemodynamics are altered only locally, and without apparent change in metabolic (i.e. heat-induced) demand. The concurrent decline in cardiac output and LV twist during partial arterial occlusion despite the increased peripheral demand caused by heat stress suggests that LV twist may be involved in the protective sensing of heart muscle stress that can override the provision of the required cardiac output. Whether left ventricular (LV) twist and untwisting rate (LV twist mechanics) respond to localised, peripheral, non-metabolic changes in arterial haemodynamics within an individual's normal afterload range is presently unknown. Furthermore, previous studies indicate that LV twist mechanics may override the provision of cardiac output, but this hypothesis has not been examined purposefully. Therefore, we acutely altered local peripheral arterial haemodynamics in 11 healthy humans (women/men n = 3/8; age 26 ± 5 years) by bilateral arm heating (BAH). Ultrasonography was used to examine arterial haemodynamics, LV twist mechanics and the twist-to-shortening ratio (TSR). To determine the arterial function-dependent contribution of LV twist mechanics to cardiac output, partial blood flow restriction to the arms was applied during BAH (BAHBFR ). Bilateral arm heating increased arm skin temperatures [change (Δ) +6.4 ± 0.9°C, P 0.05), concomitant to increases in brachial artery blood flow (Δ 212 ± 77 ml, P 0.05). Subsequently, BAHBFR reduced all parameters to preheating levels, except for TSR and heart rate, which remained at BAH levels. In conclusion, LV twist mechanics responded to local peripheral arterial haemodynamics within the normal afterload range, in part independent of TSR and heart rate. The findings suggest that LV twist mechanics may be more closely associated with intrinsic sensing of excessive pressure stress rather than being associated with the delivery of adequate cardiac output.

Letter published in Clinical Research in Cardiology on 10 August 2017, available at: https://doi.org/10.1007/s00392-017-1143-9.

Purpose We previously showed that cerebrovascular reactivity (CVR) is reduced in heart failure (HF) patients and does not improve after left ventricular assist device (LVAD) HeartMate II (HMII) implantation, possibly because of low pulsatile physiology. Therefore, it is possible that the artificial pulse of the latest generation LVAD, the HeartMate3 (HM3), restores normal CVR. HM3 patients will have an increased CVR to a CO2-retention challenge compared with HF and HMII. Methods A total of 79 subjects (17 healthy, 30 HF, 15 HMII and 17 HM3) underwent angle-corrected transcranial Doppler sonography. Middle cerebral artery (MCA) velocity profiles were recorded before and at the end of a 30s breath hold. Mean flow velocity (MFV), peak flow velocity (Vmax), minimal flow velocity (Vmin), Pulsatility Index (PI) and Resistance Index (RI) were quantified. Statistical differences were determined using 2-way ANOVA (Breathhold x group). Results At baseline, HF patients with and without LVAD implantation had a decreased Vmax, MFV, PI and RI compared to healthy (all P Conclusion HM3 patients have a significantly improved CVR to a CO2-retention challenge compared with HMII patients. However, the acute CVR is not altered by the artificial pulse. Since CVR of HM3 patients remains reduced compared with healthy controls, further research is needed to understand the pathophysiology of cerebrovascular complications in LVAD.

Purpose Lack of nocturnal blood pressure (BP) reduction (BP dipping) has been associated with cerebrovascular and cardiovascular events in the general population. However, the effect of a deranged circadian BP variability between day and night has never been studied in patients on left ventricular assist device (LVAD) support, where stroke still represents a major complication. We hypothesized that decreased BP dipping significantly increases the risk of stroke in patients on LVAD support. Methods HeartMate II (HMII) outpatients were prospectively studied with an ambulatory BP monitor (Mobil-O-Graph) previously validated in this patient population. Systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were recorded every 30 minutes during the day and every hour during the night for 24 hours. Circadian patterns, expressed as the percentage of nocturnal SBP, DBP, and MAP reduction from daytime values, were assessed in Cox regression models with stroke as primary endpoint. Results 29 patients were studied (age 59 ±15 yrs, 76% male, 38% ischemic, 69% DT). 6 patients (20%) experienced a stroke 879±591 days post LVAD implant. Nocturnal reductions of SBP, DBP, and MAP were 5.0 ± 6.1%, 5.0 ± 5.6% and 5.0 ± 5.5%, respectively. Preserved nocturnal reductions of SBP (HR 0.790 [95% CI 0.658 - 0.949]), DBP (HR 0.707 [95% CI 0.559 - 0.894]) and MAP (HR 0.703 [95% CI 0.554 - 0.894]) were associated with a decreased risk of stroke. When patients were grouped by the median nocturnal reduction in MAP (5.4%), patients with reduced dipping had a significantly greater risk of stroke (Figure 1). Conclusion This study is the first to indicate that reduced BP dipping at night increases the risk of stroke in patients on HMII support. Further studies are warranted to investigate, mechanistically, the relationship between reduced BP dipping and sympathetic nervous system activation, and, clinically, its association with the risk of stroke in patients on HM3 support.

Purpose The optimal method for blood pressure (BP) measurement among pts implanted with HeartMate 3 (HM3), a centrifugal pump that features an artificial pulse, is presently unknown. We aimed to: 1) assess success rate and validity of Doppler opening BP (DOBP) and automated BP (ABP) monitor; 2) test a novel approach to estimate mean arterial pressure (MAP) by combining DOBP and HM3 parameters. Methods BP and HM3 parameters (Speed, Power, Pulsatility Index [PI], Flow) were prospectively collected in a derivation cohort (DC, n=50) and a validation cohort (VC, n=11). BP was measured by arterial line (A-line) in all pts. DOBP and ABP were concurrently measured in a subgroup of DC (DCs, n=31) and in VC. In DC, a multiple linear regression model was fit with A-line systolic BP (SBP) and HM3 parameters as predictor variables and A-line MAP as the dependent variable to derive the HM3 MAP Formula. In DCs and VC, the accuracy of the Formula in estimating A-line MAP was tested using DOBP as non-invasive equivalent of A-line SBP. Mean observed differences (MOD) and mean absolute differences (MAD) against A-line were calculated for each method. Results The success rate for Doppler and ABP monitor was 100% and 49%, respectively. In DCs, DOBP reflected A-line SBP (MAD 4.6, MOD +1.7 mmHg) but markedly overestimated A-line MAP (Fig A). MAD and MOD of ABP monitor were 7.7 and +3.5 and 7.0 and +1.1 mmHg for SBP and MAP, respectively (Fig B). In DC, the best model to predict A-line MAP included PI and Flow in addition to A-line SBP (HM3 MAP Formula, r2=0.77). In DCs, the Formula accurately predicted A-line MAP when using A-line SBP (Fig C) and DOBP (Fig D). In a preliminary analysis of VC, the accuracy of the Formula was similar (MAD: A-line SBP 4.1, DOBP 6.8 mmHg). Conclusion In HM3 pts, DOBP accurately estimates SBP, but overestimates MAP. ABP monitor has limited success rate and accuracy, possibly due to the artificial pulse. The HM3 MAP Formula represents a uniformly successful and valid tool to estimate MAP by combining DOBP and pump parameters.