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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.

Dehydration accrued during intense prolonged whole‐body exercise in the heat compromises peripheral blood flow and cardiac output (Q˙). A markedly reduced stroke volume (SV) is a key feature of the dehydration‐induced cardiovascular strain, but whether the lower output of the heart is mediated by peripheral or cardiac factors remains unknown. Therefore, we repeatedly quantified left ventricular (LV) volumes, LV mechanics (LV twist, a marker of systolic muscle function, and LV untwisting rate, an independent marker of LV muscle relaxation), left intra‐ventricular pressure gradients, blood volume and peripheral blood flow during 2 hr of cycling in the heat with and without dehydration (DEH: 4.0 ± 0.2% body mass loss and EUH: euhydration control, respectively) in eight participants (three females and five males). While brachial and carotid blood flow, blood volume, SV, LV end‐diastolic volume (LVEDV), cardiac filling time, systemic vascular conductance and Q˙ were reduced in DEH compared to EUH after 2 hr, LV twist and untwisting rate tended to be higher (p = .09 and .06, respectively) and intra‐ventricular pressure gradients were not different between the two conditions (p = .22). Furthermore, LVEDV in DEH correlated strongly with blood volume (r = .995, p, Dehydration reduces stroke volume and cardiac output during intense prolonged exercise in the heat, but the underlying peripheral and cardiac mechanisms are not fully understood. We show that the reduced stroke volume accounting for the impaired cardiac output is closely associated with diminished left ventricular filling secondary to decreased peripheral blood flow and volume, compromised venous return, and reduced cardiac filling time. These findings highlight the importance of peripheral mechanisms in cardiac performance during exercise.

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

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.

Purpose It is well established that continuous-flow left ventricular assist devices (LVAD) reduce pulsatility in the circulation. Consequently, the addition of an ‘artificial pulse’ to the HeartMate3 (HM3) LVAD has been expected to increase pulsatility. Yet, there has been no prospective study that has examined arterial hemodynamics of HM3 patients across the whole circulation, from large to muscular and microcirculatory arteries.Compared with HMII patients, HM3 patients will have a significantly increased arterial pulsatility across the whole circulation, and similar pulsatility to healthy individuals. Methods Pulsatility index (PI), peak systolic velocity (PSV), minimum velocity (Vmin) and mean flow velocity (MFV) of the common carotid, middle cerebral and central retinal arteries were quantified with angle-corrected 2D ultrasound in 141 volunteers (32 healthy controls, 42 heart failure (HF), 28 HM II, and 39 HM3 patients). To test the study hypothesis, data were statistically evaluated using 1-way ANOVA with Tukey's honestly significant difference test. Results Across all three artery locations, both PI and PSV of HM3 patients were significantly lower compared with healthy controls and HF (all P 0.05, Fig.1). Similarly, Vmin and MFV were not significantly different between HM3 and HMII (all P>0.05). Conclusion Despite the presence of an ‘artificial pulse’, pulsatility in patients implanted with the HM3 remains significantly lower than healthy controls and similar to HM II patients. Importantly, the lack of increased pulsatility in HM3 was explained by the flow pattern caused by the artificial pulse, which did not increase peak systolic velocity. These findings add insight into the remaining cardiovascular complications in HM3 patients and warrant further investigation.

Purpose While the impact of mean arterial pressure (MAP) on adverse events during left ventricular assist device (LVAD) support has been well established, there remains significant controversy regarding the impact of pulse pressure (PP) on clinical outcomes. We evaluated the impact of PP on post-implant hemocompatibility related adverse events (HRAE). Methods Using the INTERMACS registry, we identified patients who received a primary, durable continuous-flow LVAD with distinct systolic and diastolic blood pressure readings at 3-months post-implant. Patients requiring mechanical right ventricular assist devices or inotropic support were excluded. Patients were then stratified into low, medium, and high pulsatility tertiles. Kaplan-Meier survival estimates and Cox Proportional Hazard Models were used to assess the impact of pulsatility on HRAEs. Results A total of 4745 patients were classified into low (n=1508), medium (n=1675), and high (n=1562) pulsatility groups. There was no correlation between PP and MAP in this population (Figure 1A) and no clinically significant difference in MAP between the groups. Significant pre-implant determinants of pulsatility included female sex, BMI, race, device type, and peripheral vascular disease. Patients with lower pulsatility had more RV dysfunction and higher pro-BNP levels as compared to those with higher pulsatility. PP was a significant risk factor for stroke (HR: 1.09, CI: 1.04 - 1.15, p=0.001 per 10mmHg increase) independent of MAP. Patients with high MAP and high PP had the highest stroke risk (Figure 1B). PP was not associated with GI bleeding, device thrombosis. thromboembolic events, or post-implant survival. Conclusion High PP is associated with increased risk of stroke during LVAD support. Pulsatility may represent an additional therapeutic target in this patient population.

Background: Chronic obstructive pulmonary disease (COPD) is characterised by airway limitation which is an independent predictor of increased cardiovascular (CV) risk and mortality [1]. COPD is associated with increased arterial stiffness [2] and increased incidence of all stroke subtypes [3]. However, the mechanism linking this association is not fully understood. The study aims to identify predictors of middle cerebral artery pulsatility (MCAPI) in COPD and controls. Method: MCAPI was measured using transcranial Doppler ultrasound. Aortic pulse wave velocity (aPWV) and central pulse pressure (CPP) were measured using the SphygmoCor system. Forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) was measured using spirometry. Use of CV acting medications were recorded. Result: 45 COPD patients and 50 healthy controls were included in the analyses. Age, gender, CPP and MCAPI were similar between groups, however the COPD patients showed higher aPWV, lower FEV1/FVC and were on more CV acting medication (all, p < 0.05). In COPD, MCAPI was significantly associated with CPP (r = 0.433, p = 0.003) and FEV1/FVC (r = 0.330, p = 0.027), but not aPWV. In controls, MCAPI was significantly associated with CPP (r = 0.601, p = 0.001) and aPWV (r = 0.452, p = 0.001). However, Stepwise Multiple Regression Analysis illustrated that only CPP remained an independent predictor of MCAPI (p = 0.003), in a model which included age, aPWV, FEV1/FVC and use of CV acting medications. Conclusion: Within the COPD group, CPP was independently associated with MCAPI, even when accounting for use of CV acting medications. However, the interaction between CV acting medications and the relationship between aPWV and MCAPI remains unclear and needs further investigations.

Background: The MOMENTUM3 trial1 has revealed superiority of the novel HeartMate3 (HM3) left ventricular assist device (LVAD) compared with the HM2, with a significantly reduced occurrence of cerebrovascular accidents. Thus, cerebral autoregulation may be improved in HM3 compared with HM II patients, possibly because of altered microcirculatory haemodynamics associated with the in-built speed modulation (‘pulsatility’) of the HM3 device. Methods: Angle-corrected Doppler ultrasound images of the middle cerebral artery (MCA) were recorded before and at the end of a 30s breathhold test in healthy controls (n = 17), heart failure (HF n = 18), HM2 (n = 10) and HM3 (n = 17) patients. Microcirculatory haemodynamics as represented by the central retinal artery (CRA) were also quantified (Controls = 33, HF = 27, HM2 = 23, HM3 = 31). Data were analysed for Time-Averaged Maximum flow velocity (TAMAX), peak flow velocity (Vmax), minimum flow velocity (Vmin), Pulsatility Index (PI) and Resistance Index (RI, Table 1). Table 1Haemodynamics in the middle cererbral artery (MCA) and the central retinal artery (CRA) between HeartMate2 and HeartMate3 patients Healthy controls (n = 33) Heart failure (n = 27) HeartMate II (n = 23) HeartMate3 (average) (n = 31) HeartMate3 (no speed modulation) (n = 31) HeartMate3 (with speed modulation) (n = 31) Middle Cerebral Artery TAMAX (cm/s) 58 ± 15 48 ± 13 45 ± 15 48 ± 19 48 ± 19 46 ± 18 Vmax (cm/s) 92 ± 22 78 ± 20 55 ± 19*# 55 ± 21*# 54 ± 21*# 55 ± 22*# Vmin (cm/s) 39 ± 12 29 ± 11 37 ± 16 39 ± 14 44 ± 16# 32 ± 13 Pulsatility index 0.88 ± 0.18 1.05 ± 0.31* 0.40 ± 0.24*# 0.34 ± 0.14*# 0.21 ± 0.12*#$ 0.56 ± 0.24*# Resistance index 0.57 ± 0.07 0.60 ± 0.11 0.29 ± 0.14*# 0.16 ± 0.09*#$ 0.17 ± 0.10*#$ 0.14 ± 0.09*#$ Central retinal artery TAMAX (cm/s) 6 ± 1 5 ± 2 6 ± 3 7 ± 3 7 ± 4 6 ± 4 Vmax (cm/s) 12 ± 3 11 ± 6 8 ± 4* 8 ± 4* 8 ± 4* 8 ± 4* Vmin (cm/s) 3 ± 1 3 ± 1 5 ± 2 5 ± 3 6 ± 3*# 4 ± 4 Pulsatility index 1.60 ± 0.45 1.42 ± 0.40 0.58 ± 0.26*# 0.49 ± 0.21*# 0.32 ± 0.17*# 0.79 ± 0.35*# Resistance index 0.75 ± 0.09 0.70 ± 0.11 0.38 ± 0.15*# 0.22 ± 0.11*#$ 0.24 ± 0.12*#$ 0.20 ± 0.13*#$ *p < 0.05 compared with healthy controls; #p < 0.05 compared with Heart Failure; $p < 0.05 compared with HeartMate II. Results: Breathhold significantly increased TAMAX, Vmax and Vmin in all groups except HM II patients (Figure 1A). Conversely, PI decreased slightly in all groups while RI was maintained. The greater breathhold response in HM3 compared with HM2 patients was not attributable to the in-built pump-speed modulation (Figure 1B), however, HM3 had a consistently lower RI in the MCA and CRA. Figure 1(A) Time-averaged maximum flow velocity in the middle cerebral artery of healthy controls and patient groups in response to a 30-s breathhold test. (B) Breakdown of the responses in HM3 patients, comparing beats with and without added pulsatility. Conclusion: Although reduced compared with healthy controls, HF and HM3 patients have a significantly greater metabolic cerebral vasoreactivity compared with HM2 patients. The 60% greater diastolic flow velocity in the microcirculation of both LVAD groups compared to healthy controls may alter gas exchange in the microcirculation. Future studies should examine the role of altered RI in HM3 patients.

Background\ud Cardiac rehabilitation (CR) exercise training is beneficial after myocardial infarction (MI). Whilst the peripheral adaptations to training are well defined, little is known regarding the effect on left ventricular (LV) remodelling, particularly LV function. Efficient LV ejection and filling is achieved through deformation and rotation of the myocardium in systole and diastole – LV mechanics. The response of LV mechanics to CR exercise training in MI patients is unknown.\ud \ud Methods\ud In this observational exploratory study, 36 (of 40 enrolled) male, MI patients completed either 10-weeks of twice-weekly gym based cardiovascular exercise at 60–80% VO2peak (n = 18), or a non-exercise control period (n = 18). Cardiopulmonary exercise testing and speckle tracking echocardiography were performed at baseline and 10 weeks.\ud \ud Results\ud Compared to the non-exercise group, VO2peak improved with CR exercise training (Difference: +4.28 [95% CI: 1.34 to 7.23] ml.kg−1.min−1, P = 0.01). Neither conventional LV structural or functional indices, nor LV global longitudinal strain, significantly changed in either group. In contrast, LV twist and twist velocity decreased in the exercise group and increased in the non-exercise group (Difference: −3.95° [95% CI: −7.92 to 0.03°], P = 0.05 and −19.2°.s−1 [95% CI: −35.9 to −2.7°.s−1], P = 0.02, respectively).\ud \ud Conclusion\ud In MI patients who completed CR exercise training, LV twist and twist velocity decreased, whereas these parameters increased in patients who did not exercise. These preliminary data may indicate reverse LV functional remodelling and improved functional reserve. The assessment of LV twist may serve as an indicator of the therapeutic benefit of CR exercise training and should be investigated in larger trials.

The influence of cardiorespiratory fitness (CRF) on arterial stiffness in young adults remains equivocal. Beyond conventional measures of arterial stiffness, 2D strain imaging of the common carotid artery (CCA) provides novel information related to the intrinsic properties of the arterial wall. Therefore, this study aimed to assess the effect of CRF on both conventional indices of CCA stiffness and 2D strain parameters, at rest and following a bout of aerobic exercise in young healthy males. Short‐axis ultrasound images of the CCA were recorded in 34 healthy men [22 years (95%CI, 19–22)] before, and immediately after 5‐minutes of aerobic exercise (40% VO2max). Images were analysed for arterial diameter, peak circumferential strain (PCS), and peak systolic and diastolic strain rates (S‐SR, D‐SR). Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) were simultaneously assessed and Petersons' elastic modulus (Ep) and Beta stiffness (β1) were calculated. Participants were separated post hoc into moderate and high fitness groups [VO2max: 48.9 ml.kg‐1 min‐1 (95%CI, 44.7–53.2) vs. 65.6 ml.kg‐1 min‐1 (95%CI, 63.1–68.1); P < 0.001]. Ep and β1 were similar between groups at baseline (P > 0.13) but were elevated in the moderate‐fitness group post‐exercise (P < 0.04). PCS and S‐SR were elevated in the high‐fitness group at both time‐points [3.0% (95%CI = 1.2, 4.9); P = 0.002; 0.401/s (95%CI = 0.085, 0.72); P = 0.02, respectively]. No group differences were observed in diameter, HR, SBP, DBP or D‐SR throughout the protocol (P > 0.05). High‐fit individuals exhibit elevated CCA PCS and S‐SR, which may reflect training‐induced adaptations that help to buffer the rise in pulse‐pressure and stroke volume during exercise.

Article published in Journal of Thoracic and Cardiovascular Surgery on 12 March 2018, available open access at: https://doi.org/10.1016/j.jtcvs.2017.10.160.

Clinical and experimental studies have suggested that the duration of left ventricular assist device (LVAD) support may affect remodeling of the failing heart. We aimed to 1) characterize the changes in Ca2+/calmodulin-dependent protein kinase type-IIδ (CaMKIIδ), growth signaling, structural proteins, fibrosis, apoptosis, and gene expression before and after LVAD support and 2) assess whether the duration of support correlated with improvement or worsening of reverse remodeling. Left ventricular apex tissue and serum pairs were collected in patients with dilated cardiomyopathy ( n = 25, 23 men and 2 women) at LVAD implantation and after LVAD support at cardiac transplantation/LVAD explantation. Normal cardiac tissue was obtained from healthy hearts ( n = 4) and normal serum from age-matched control hearts ( n = 4). The duration of LVAD support ranged from 48 to 1,170 days (median duration: 270 days). LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Increased CaMKIIδ phosphorylation, nuclear myocyte enhancer factor 2, and cardiac MSTN significantly correlated with the duration of support. Phosphorylation of SMAD2 and apoptosis decreased with a shorter duration of LVAD support but increased with a longer duration of LVAD support. Further study is needed to define the optimal duration of LVAD support in patients with dilated cardiomyopathy. NEW & NOTEWORTHY A long duration of left ventricular assist device support may be detrimental for myocardial recovery, based on myocardial tissue experiments in patients with prolonged support showing significantly worsened activation of Ca2+/calmodulin-dependent protein kinase-IIδ, increased nuclear myocyte enhancer factor 2, increased myostatin and its signaling by SMAD2, and apoptosis as well as sustained histone deacetylase-4 phosphorylation, structural protein dysregulation, and fibrosis.

Purpose: In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms. Methods: Twenty-four women with early stage breast cancer were randomly assigned to perform a 30-min, vigorous-intensity treadmill bout 24 h prior to each of four doxorubicin-containing chemotherapy treatments or to usual care. Established echocardiographic and circulating biomarkers of subclinical cardiotoxicity, as well as blood pressure and body weight were measured before the first and 7–14 days after the last treatment. The Rotterdam symptom checklist was used to assess patient-reported symptoms. Results: The exercise and usual care groups did not differ in the doxorubicin-related change in longitudinal strain, twist, or cardiac troponin. However, the four total exercise bouts prevented changes in hemodynamics (increased cardiac output, resting heart rate, decreased systemic vascular resistance, p < 0.01) and reduced body weight gain, prevalence of depressed mood, sore muscles, and low back pain after the last treatment (p < 0.05) relative to the usual care group. No adverse events occurred. Conclusions: An exercise bout performed 24 h prior to every doxorubicin treatment did not have an effect on markers of subclinical cardiotoxicity, but had a positive systemic effect on hemodynamics, musculoskeletal symptoms, mood, and body weight in women with breast cancer. A single exercise bout prior to chemotherapy treatments may be a simple clinical modality to reduce symptoms and weight gain among women with breast cancer.

Purpose Blood flow through the left ventricular assist device (LVAD) is dependent on the rotation speed of the impeller, and inversely dependent on the differential pressure across the LVAD (HQ relationship). We developed a novel approach to estimate intraventricular pressure difference (IVPD) in patients with LVAD and assess the change of IVPD according to pump speed during ramp study. Methods We developed in-house code of 1-dimensional incompressible Euler equation written in MATLAB (MathWorks, Natick, MA, USA) which allows us to measure IVPD by analyzing transesophageal echocardiographic images. Color M-mode images in mid-esophageal long axis view were obtained at 3 different pump speeds (low, optimized, high) in 10 patients who had LVAD implant (Figure). The optimal rotation speed was defined by stable hemodynamic conditions and the septal shape on transesophageal imaging. Pairwise comparison between each group was performed using Steel-Dwass analysis. Results Images were successfully obtained in all patients. Median IVPD values were 0.88 mmHg [IQR 0.73 - 1.02] at pre-LVAD implant, 1.86 mmHg [IQR 1.50 - 2.15] at low speed, 2.12 mmHg [IQR 1.72 - 2.71] at optimal speed, 2.09 mmHg [IQR1.72 - 2.31] at high speed, respectively (figure). There was significant difference between pre-implantation and the remaining 3 groups ( p Conclusion These data illustrate a novel approach to estimate IVPD during early diastole in patients with LVAD. Importantly, data suggests that setting of pump speed can be informed by analyzing IVPD during early diastole.

Impaired myocardial systolic contraction and diastolic relaxation have been suggested as possible mechanisms contributing to the decreased stroke volume (SV) observed at high altitude (HA). To determine whether intrinsic myocardial performance is a limiting factor in the generation of SV at HA, we assessed left ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy participants (aged 32 ± 7; mean ± SD) at rest and during exercise at sea level (SL; 344 m) and after 10 days at 5,050 m. In contrast to SL, LV end-diastolic volume was ∼19% lower at rest ( P = 0.004) and did not increase during exercise despite a greater untwisting velocity. Furthermore, resting SV was lower at HA (∼17%; 60 ± 10 vs. 70 ± 8 ml) despite higher LV twist (43%), apical rotation (115%), and circumferential strain (17%). With exercise at HA, the increase in SV was limited (12 vs. 22 ml at SL), and LV apical rotation failed to augment. For the first time, we have demonstrated that EDV does not increase upon exercise at high altitude despite enhanced in vivo diastolic relaxation. The increase in LV mechanics at rest may represent a mechanism by which SV is defended in the presence of a reduced EDV. However, likely because of the higher LV mechanics at rest, no further increase was observed up to 50% peak power. Consequently, although hypoxia does not suppress systolic function per se, the capacity to increase SV through greater deformation during submaximal exercise at HA is restricted.

This article was published in Experimental Physiology on 6 May 2015 (online), freely available at http://dx.doi.org/10.1113/EP085081

Background: High pulsatility index (PI) in the cerebral circulation has been associated with increased prevalence of stroke (1). Interestingly, heart failure (HF) patients implanted with continuous-flow left ventricular assist devices (CF-LVADs) have increased rates of stroke despite presenting with dramatically lower pulse pressures compared with healthy individuals (20 mmHg vs. 30–40 mmHg). Characterising and understanding flow velocity profiles of the middle cerebral artery (MCA) may provide a useful and local marker of pulsatile energy transmitted into the brain of HF and CF-LVAD patients. Methods: PI and resistance index (RI) were quantified from Duplex ultrasound images (2D and pulsed-wave Doppler) of the MCA obtained in four heart failure patients (HF; 68 ± 7 yrs), eight CF-LVAD patients (59 ± 4 yrs) and 20 healthy controls (51 ± 7 yrs). Results: Compared with healthy controls, PI of the MCA was actually higher in the HF group (0.72 ± 0.16 vs. 1.32 ± 0.17, P < 0.0001), but markedly lower in patients on CF-LVAD (0.36 ± 0.21, P < 0.0001). However, RI was similar between healthy controls and HF patients (P > 0.05), and only lower in CF-LVAD patients (P < 0.0001). Conclusions: PI in the MCA is significantly higher in HF but markedly lower in CF-LVAD patients, relative to healthy controls. The higher PI in HF does not appear to be associated with an altered RI. Future work should examine the cerebrovascular outcomes associated with varying levels of pulsatility and resistance in both HF and CF-LVAD patients.

Limited data are available on hemodynamic responses to anesthetic protocols in wild-born chimpanzees (Pan troglodytes). Accordingly, this study characterized the heart rate (HR) and blood pressure responses to four anesthetic protocols in 176 clinically healthy, wild-born chimpanzees undergoing routine health assessments. Animals were anesthetized with medetomidine-ketamine (MK) (n = 101), tiletamine-zolazepam (TZ) (n = 30), tiletamine-zolazepam-medetomidine (TZM) (n = 24), or medetomidine-ketamine (maintained with isoflurane) (MKI) (n = 21). During each procedure, HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were regularly recorded. Data were grouped according to anesthetic protocol, and mean HR, SBP, and DBP were calculated. Differences between mean HR, SBP, and DBP for each anesthetic protocol were assessed using the Kruskall-Wallis test and a Dunn multiple comparisons post hoc analysis. To assess the hemodynamic time course response to each anesthetic protocol, group mean data (±95% confidence interval [CI]) were plotted against time postanesthetic induction. Mean HR (beats/min [CI]) was significantly higher in TZ (86 [80-92]) compared to MKI (69 [61-78]) and MK (62 [60-64]) and in TZM (73 [68-78]) compared to MK. The average SBP and DBP values (mm Hg [CI]) were significantly higher in MK (130 [126-134] and 94 [91-97]) compared to TZ (104 [96-112] and 58 [53-93]) and MKI (113 [103-123] and 78 [69-87]) and in TZM (128 [120-135] and 88 [83-93]) compared to TZ. Time course data were markedly different between protocols, with MKI showing the greatest decline over time. Both the anesthetic protocol adopted and the timing of measurement after injection influence hemodynamic recordings in wild-born chimpanzees and need to be considered when monitoring or assessing cardiovascular health.

To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist, and untwisting rate ("LV mechanics").LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7-12 s) double-leg press exercise at two intensities (30% and 60% of maximum strength, one-repetition maximum). Speckle tracking analysis generated LV strain, twist, and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated.Responses in both exercise trials were statistically similar (P0.05). During effort, stroke volume decreased, whereas SVR and LV wall stress increased (P0.05). Immediately after effort, stroke volume returned to baseline, whereas SVR and wall stress decreased (P0.05). Similarly, acute exercise was accompanied by a significant decrease in systolic parameters of LV muscle mechanics (P0.05). However, diastolic parameters, including LV untwisting rate, were statistically unaltered (P0.05). Immediately after exercise, systolic LV mechanics returned to baseline levels (P0.05) but LV untwisting rate increased significantly (P0.05).A single, acute bout of double-leg press resistance exercise transiently reduces systolic LV mechanics, but increases diastolic mechanics after exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes.

An increasing number of end-stage heart failure patients are now implanted with continuous-flow left ventricular assist devices (CF-LVADs). Although this therapeutic approach is associated with improved clinical outcomes, continuous flow physiology reduces arterial pulse pressure and pulsatility to an extent that is unique to this population. Recent data suggest that high blood pressure (BP) contributes to life-threatening complications such as pump thrombosis and stroke of CF-LVAD patients. However, limited understanding of the distinct hemodynamics of these pumps makes measurement and, consequently, medical management of BP quite challenging. Here, we review the evolution of LVAD design, the impact of CF-LVAD flow, and "artificial pulse" technology on hemodynamics and BP measurement, as well as suggest new approaches for the assessment and interpretation of the unique physiology of modern LVADs.

This article was published in The Journal of Heart and Lung Transplantation on 05 March 2017 (online), available at http://dx.doi.org/10.1016/j.healun.2017.02.026