Attenuating intrathoracic pressure swings decreases cardiac output at different intensities of exercise.

Intrathoracic pressure (ITP) swings that permit spontaneous ventilation have physiological implications for the heart. We sought to determine the effect of respiration on cardiac output ( Q ̇ $\dot Q$ ) during semi-supine cycle exercise using a proportional assist ventilator to minimize ITP changes and lower the work of breathing (Wb ). Twenty-four participants (12 females) completed three exercise trials at 30%, 60% and 80% peak power (Wmax ) with unloaded (using a proportional assist ventilator, PAV) and spontaneous breathing. Intrathoracic and intraabdominal pressures were measured with balloon catheters placed in the oesophagus and stomach. Left ventricular (LV) volumes and Q ̇ $\dot Q$ were determined via echocardiography. Heart rate (HR) was measured with electrocardiogram and a customized metabolic cart measured oxygen uptake ( V ̇ O 2 ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Oesophageal pressure swings decreased from spontaneous to PAV breathing by -2.8 ± 3.1, -4.9 ± 5.7 and -8.1 ± 7.7 cmH2 O at 30%, 60% and 80% Wmax , respectively (P = 0.01). However, the decreases in Wb were similar across exercise intensities (27 ± 42 vs. 35 ± 24 vs. 41 ± 22%, respectively, P = 0.156). During PAV breathing compared to spontaneous breathing, Q ̇ $\dot Q$ decreased by -1.0 ± 1.3 vs. -1.4 ± 1.4 vs. -1.5 ± 1.9 l min-1 (all P < 0.05) and stroke volume decreased during PAV breathing by -11 ± 12 vs. -9 ± 10 vs. -7 ± 11 ml from spontaneous breathing at 30%, 60% and 80% Wmax , respectively (all P < 0.05). HR was lower during PAV breathing by -5 ± 4 beats min-1 at 80% Wmax (P < 0.0001). Oxygen uptake decreased by 100 ml min-1 during PAV breathing compared to spontaneous breathing at 80% Wmax (P < 0.0001). Overall, attenuating ITPs mitigated LV preload and ejection, thereby suggesting that the ITPs associated with spontaneous respiration impact cardiac function during exercise. KEY POINTS: Pulmonary ventilation is accomplished by alterations in intrathoracic pressure (ITP), which have physiological implications on the heart and dynamically influence the loading parameters of the heart. Proportional assist ventilation was used to attenuate ITP changes and decrease the work of breathing during exercise to examine its effects on left ventricular (LV) function. Proportional assist ventilation with progressive exercise intensities (30%, 60% and 80% Wmax ) led to reductions in cardiac output at all intensities, primarily through reductions in stroke volume. Decreases in LV end-diastolic volume (30% and 60% Wmax ) and increases in LV end-systolic volume (80% Wmax ) were responsible for the reduction in stroke volume. The relationship between cardiac output and oxygen uptake is disrupted during respiratory muscle unloading.

Exertional Cardiac and Pulmonary Vascular Hemodynamics in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF), but quantitative data regarding exertional hemodynamics are lacking. OBJECTIVES: We sought to characterize exertional cardiopulmonary hemodynamics in patients with HFrEF. METHODS: We studied 35 patients with HFrEF (59 ± 12 years old, 30 males) who completed invasive cardiopulmonary exercise testing. Data were collected at rest, at submaximal exercise and at peak effort on upright cycle ergometry. Cardiovascular and pulmonary vascular hemodynamics were recorded. Fick cardiac output (Qc) was determined. Hemodynamic predictors of peak oxygen uptake (VO2) were identified. RESULTS: Left ventricular ejection fraction and cardiac index were 23% ± 8% and 2.9 ± 1.1 L/min/m2, respectively. Peak VO2 was 11.8 ± 3.3 mL/kg/min, and the ventilatory efficiency slope was 53 ± 13. Right atrial pressure increased from rest to peak exercise (4 ± 5 vs 7 ± 6 mmHg,). Mean pulmonary arterial pressure increased from rest to peak exercise (27 ± 13 vs 38 ± 14 mmHg). Pulmonary artery pulsatility index increased from rest to peak exercise, while pulmonary arterial capacitance and pulmonary vascular resistance declined. CONCLUSIONS: Patients with HFrEF suffer from marked increases in filling pressures during exercise. These findings provide new insight into cardiopulmonary abnormalities contributing to impairments in exercise capacity in this population. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03078972.

The healthy heart does not control a specific cardiac output: a plea for a new interpretation of normal cardiac function.

The current evidence suggests that the healthy heart does not sense the optimal cardiac output (Q̇) because the different organ systems that influence cardiac function do not interact to adjust their individual responses toward a specific Q̇. Consequently, it is conceivable that the complex cycle of cardiac contraction and relaxation must occur for reasons other than to produce a specific target Q̇ and that there is likely a yet undiscovered overarching principle in the cardiovascular system that explains the combined effects of the prevailing preload, afterload, and contractility. Future research should embrace the possibility of a different purpose to cardiac function than previously assumed and examine the biological capacity of this fascinating organ accordingly.

Impact of Mechanical Circulatory Support on Exercise Capacity in Patients With Advanced Heart Failure.

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.

Increased Aortic Stiffness Is Associated With Higher Rates of Stroke, Gastrointestinal Bleeding and Pump Thrombosis in Patients With a Continuous Flow Left Ventricular Assist Device.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Carotid artery structure and hemodynamics and their association with adverse vascular events in left ventricular assist device patients.

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.

THE INFLUENCE OF ANESTHESIA WITH AND WITHOUT MEDETOMIDINE ON CARDIAC STRUCTURE AND FUNCTION IN SANCTUARY CAPTIVE CHIMPANZEES (PAN TROGLODYTES).

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.

Bionic women and men - Part 2: Arterial stiffness in heart failure patients implanted with left ventricular assist devices.

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

Bionic women and men - Part 3: Right ventricular dysfunction in patients implanted with left ventricular assist devices.

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

Bionic women and men - Part 1: Cardiovascular lessons from heart failure patients implanted with left ventricular assist devices.

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

Bionic women and men - Part 4: Cardiovascular, cerebrovascular and exercise responses among patients supported with left ventricular assist devices.

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

Structural and functional cardiac profile after prolonged duration of mechanical unloading: potential implications for myocardial recovery.

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.

The effect of an aerobic exercise bout 24 h prior to each doxorubicin treatment for breast cancer on markers of cardiotoxicity and treatment symptoms: a RCT.

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.

Adaptation of myocardial twist in the remodelled athlete's heart is not related to cardiac output.

NEW FINDINGS: 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. ABSTRACT: 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 (r2  = 0.04, P = 0.33). In normoxia and hypoxia, exercise increased LV systolic mechanics in both groups (P < 0.001), but with different relationships to SV and cardiac output. Conversely to our hypothesis, hearts of different size had similar LV systolic mechanics, suggesting that similar twist, torsion and TwSR at rest and during exercise irrespective of cardiac output may be an important mechanism in healthy hearts. We hypothesise that the regulatory 'purpose' of LV twist may be related to the sensing of maximal cardiac myofibre stress, which may act as a biologically purposeful limiter to contraction.

Cardiac and haemodynamic influence on carotid artery longitudinal wall motion.

NEW FINDINGS: What is the central question of this study? Carotid artery longitudinal wall motion (CALM) is a bidirectional forward and backward motion of the arterial wall; however, there is no evidence in humans for what controls CALM despite proposals for pulse pressure, left ventricular motion and shear rate. What is the main finding and its importance? Carotid artery longitudinal wall motion responses were heterogeneous when manipulating sympathetic activation and endothelium-independent vasodilatation, leading to non-significant group responses. However, individual CALM responses were associated with left ventricular rotation and shear rate. These findings are important when interpreting changes in CALM in humans with acute or chronic experimental designs. 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, 15 healthy men (22 ± 2 years old) 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 < 0.01), apical LV rotation (P < 0.01) and carotid shear rate (P < 0.01), with no changes in CALM (P > 0.05). Likewise, 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 < 0.01), without altering CALM (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 in systolic retrograde CALM (B = -0.025, P = 0.03), whereas 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 haemodynamic factors may influence CALM in humans.

Carotid artery wall mechanics in young males with high cardiorespiratory fitness.

NEW FINDINGS: What is the central question of this study? Common carotid artery (CCA) two-dimensional strain imaging detects intrinsic arterial wall properties beyond conventional measures of arterial stiffness, but the effect of cardiorespiratory fitness on two-dimensional strain-derived indices of CCA stiffness is unknown. What is the main finding and its importance? Two-dimensional strain imaging of the CCA revealed greater peak circumferential strain and systolic strain rate in highly fit men compared with their less fit counterparts. Altered CCA wall mechanics might reflect intrinsic training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise. ABSTRACT: The influence of cardiorespiratory fitness on arterial stiffness in young adults remains equivocal. Beyond conventional measures of arterial stiffness, two-dimensional strain imaging of the common carotid artery (CCA) provides new information related to the intrinsic properties of the arterial wall. Therefore, the aim of this study was to assess the effect of cardiorespiratory fitness on both conventional indices of CCA stiffness and two-dimensional strain parameters, at rest and after a bout of aerobic exercise in young, healthy men. Short-axis ultrasound images of the CCA were recorded in 34 healthy men {22 years old [95% confidence interval (CI), 19, 22]} before and immediately after 5 min of aerobic exercise (40% of maximal oxygen consumption). Images were analysed for arterial diameter, peak circumferential strain (PCS) and peak systolic and diastolic strain rates (S-SR and D-SR). Heart rate, systolic and diastolic blood pressure were simultaneously assessed, and Peterson's elastic modulus (Ep ) and ß-stiffness (ß1 ) were calculated. Participants were separated post hoc into moderate- and high-fitness groups [maximal oxygen consumption, 48.9 (95% CI, 44.7, 53.2) versus 65.6 ml kg-1  min-1 (95% CI, 63.1, 68.1), respectively; P < 0.001]. The Ep and ß1 were similar between groups at baseline (P > 0.13) but were elevated in the moderate-fitness group postexercise (P < 0.04). The 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, and 0.401 s-1 (95% CI, 0.085, 0.72), P = 0.02, respectively]. No group differences were observed in CCA heart rate, systolic or diastolic blood pressure or D-SR throughout the protocol (P > 0.05). Highly fit individuals exhibit elevated CCA, PCS and S-SR, which might reflect training-induced adaptations that help to buffer the increase in pulse pressure and stroke volume during exercise.

Cardiac dysfunction in cancer survivors unmasked during exercise.

BACKGROUND: The cardiac dysfunction associated with anthracycline-based chemotherapy cancer treatment can exist subclinically for decades before overt presentation. Stress echocardiography, the measurement of left ventricular (LV) deformation and arterial haemodynamic evaluation, has separately been used to identify subclinical cardiovascular (CV) dysfunction in several patient groups including those with hypertension and diabetes. The purpose of the present cross-sectional study was to determine whether the combination of these techniques could be used to improve the characterisation of subclinical CV dysfunction in long-term cancer survivors previously treated with anthracyclines. MATERIALS AND METHODS: Thirteen long-term cancer survivors (36 ± 10 years) with prior anthracycline exposure (11 ± 8 years posttreatment) and 13 age-matched controls were recruited. Left ventricular structure, function and deformation were assessed using echocardiography. Augmentation index was used to quantify arterial haemodynamic load and was measured using applanation tonometry. Measurements were taken at rest and during two stages of low-intensity incremental cycling. RESULTS: At rest, both groups had comparable global LV systolic, diastolic and arterial function (all P > 0·05); however, longitudinal deformation was significantly lower in cancer survivors (-18 ± 2 vs. -20 ± 2, P < 0·05). During exercise, this difference between groups persisted and further differences were uncovered with significantly lower apical circumferential deformation in the cancer survivors (-24 ± 5 vs. -29 ± 5, -29 ± 5 vs. 35 ± 8 for first and second stage of exercise respectively, both P < 0·05). CONCLUSION: In contrast to resting echocardiography, the measurement of LV deformation at rest and during exercise provides a more comprehensive characterisation of subclinical LV dysfunction. Larger studies are required to determine the clinical relevance of these preliminary findings.

The Unique Blood Pressures and Pulsatility of LVAD Patients: Current Challenges and Future Opportunities.

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.

HEART RATE AND INDIRECT BLOOD PRESSURE RESPONSES TO FOUR DIFFERENT FIELD ANESTHETIC PROTOCOLS IN WILD-BORN CAPTIVE CHIMPANZEES (PAN TROGLODYTES).

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.

Left ventricular twist mechanics in the context of normal physiology and cardiovascular disease: a review of studies using speckle tracking echocardiography.

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.