Cardiac Output Response Research Articles

Effects of exercise training and sex on dynamic responses of O2 uptake in type 2 diabetes.

Effects of training and sex on oxygen uptake dynamics during exercise in type 2 diabetes mellitus (T2DM) are not well established. We tested the hypotheses that exercise training improves the time constant of the primary phase of oxygen uptake (τp oxygen uptake) and with greater effect in males than females. Forty-one subjects with T2DM were assigned to 2 training groups (Tmale, Tfemale) and 2 control groups (Cmale, Cfemale), and were assessed before and after a 12-week intervention period. Twelve weeks of aerobic/resistance training was performed 3 times per week, 60-90 min per session. Assessments included ventilatory threshold (VT), peak oxygen uptake, τp oxygen uptake (80%VT), and dynamic responses of cardiac output, mean arterial pressure and systemic vascular conductance (80%VT). Training significantly decreased τp oxygen uptake in males by a mean of 20% (Tmale = 42.7 ± 6.2 to 34.3 ± 7.2 s) and females by a mean of 16% (Tfemale = 42.2 ± 9.3 to 35.4 ± 8.6 s); whereas τp oxygen uptake was not affected in controls (Cmale = 41.6 ± 9.8 to 42.9 ± 7.6 s; Cfemale = 40.4 ± 12.2 to 40.6 ± 13.4 s). Training increased peak oxygen uptake in both sexes (12%-13%) but did not alter systemic cardiovascular dynamics in either sex. Training improved oxygen uptake dynamics to a similar extent in males and females in the absence of changes in systemic cardiovascular dynamics. Novelty Similar training improvements in oxygen uptake dynamics were observed in males and females with T2DM. In both sexes these improvements occurred without changes in systemic cardiovascular dynamics.

Effect of Lower Body Negative Pressure on Phase I Cardiovascular Responses at Exercise Onset.

We hypothesised that vagal withdrawal and increased venous return interact in determining the rapid cardiac output (CO) response (phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood distribution to the heart by muscle pump action and reduce resting vagal activity. We expected a larger increase in stroke volume (SV) and smaller for heart rate (HR) at progressively stronger LBNP levels, therefore CO response would remain unchanged. To this aim ten young, healthy males performed a 50 W exercise in supine position at 0 (Control), −15, −30 and −45 mmHg LBNP exposure. On single beat basis, we measured HR, SV, and CO. Oxygen uptake was measured breath-by-breath. Phase I response amplitudes were obtained applying an exponential model. LBNP increased SV response amplitude threefold from Control to −45 mmHg. HR response amplitude tended to decrease and prevented changes in CO response. The rapid response of CO explained that of oxygen uptake. The rapid SV kinetics at exercise onset is compatible with an increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, one acting on SV, the other on HR.

How to detect a positive response to a fluid bolus when cardiac output is not measured?

BackgroundVolume expansion is aimed at increasing cardiac output (CO), but this variable is not always directly measured. We assessed the ability of changes in arterial pressure, pulse pressure variation (PPV) and heart rate (HR) or of a combination of them to detect a positive response of cardiac output (CO) to fluid administration.MethodsWe retrospectively included 491 patients with circulatory failure. Before and after a 500-mL normal saline infusion, we measured CO (PiCCO device), HR, systolic (SAP), diastolic (DAP), mean (MAP) and pulse (PP) arterial pressure, PPV, shock index (HR/SAP) and the PP/HR ratio.ResultsThe fluid-induced changes in HR were not correlated with the fluid-induced changes in CO. The area under the receiver operating characteristic curve (AUROC) for changes in HR as detectors of a positive fluid response (CO increase ≥ 15%) was not different from 0.5. The fluid-induced changes in SAP, MAP, PP, PPV, shock index (HR/SAP) and the PP/HR ratio were correlated with the fluid-induced changes in CO, but with r < 0.4. The best detection was provided by increases in PP, but it was rough (AUROC = 0.719 ± 0.023, best threshold: increase ≥ 10%, sensitivity = 72 [66–77]%, specificity = 64 [57–70]%). Neither the decrease in shock index nor the changes in other indices combining changes in HR, shock index, PPV and PP provided a better detection of a positive fluid response than changes in PP.ConclusionA positive response to fluid was roughly detected by changes in PP and not detected by changes in HR. Changes in combined indices including the shock index and the PP/HR ratio did not provide a better diagnostic accuracy.

The neurohormonal basis of pulmonary hypertension in heart failure with preserved ejection fraction

Pulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve. Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = -0.52 and -0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s' and e' tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e', r = -0.59 and -0.67, both P < 0.001), reduced cardiac output responses to exercise (r = -0.59 and -0.61, both P < 0.0001), and more severely impaired peak VO2 (r = -0.60 and -0.67, both P < 0.0001). Subjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype. NCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search.

Cardiopulmonary Exercise Testing, Impedance Cardiography, and Reclassification of Risk in Patients Referred for Heart Failure Evaluation

An impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which impedance cardiography (ICG) during exercise in combination with cardiopulmonary exercise test (CPX) responses reclassified risk for adverse events in patients with HF. CPX and ICG were performed in 1236 consecutive patients (48±15 years) evaluated for HF. Clinical, ICG and CPX variables were acquired at baseline and subjects were followed for the composite outcome of cardiac-related death, hospitalization for worsening HF, cardiac transplantation, and left ventricular assist device implantation. Cox proportional hazards analyses including clinical, noninvasive hemodynamic, and CPX variables were performed to determine their association with the composite endpoint. Net reclassification improvement (NRI) was calculated to quantify the impact of adding hemodynamic responses to a model including established CPX risk markers on reclassifying risk. There were 422 events. Among CPX variables, peak VO2 and indices of ventilatory inefficiency (VE/VCO2 slope, oxygen uptake efficiency slope) were significant predictors of risk for adverse events. Among hemodynamic variables, change in cardiac index, peak cardiac time interval, and peak left cardiac work index were the strongest predictors of risk. Having 5 impaired CPX and ICG responses to exercise yielded a sevenfold higher risk for adverse events compared with having no abnormal responses. Combining ICG responses to CPX resulted in NRIs ranging between 0.34 and 0.89, attributable to better reclassification of events. Cardiac hemodynamics determined by ICG complement established CPX measures in reclassifying risk among patients with HF.

Autonomic cardiovascular control changes in recent heart transplant recipients lead to physiological limitations in response to orthostatic challenge and isometric exercise

PurposeHeart transplantation causes denervation of the donor heart, but the consequences for cardiovascular homeostasis remain to be fully understood. The present study investigated cardiovascular autonomic control at supine rest, during orthostatic challenge and during isometric exercise in heart transplant recipients (HTxR).MethodsA total of 50 HTxRs were investigated 7–12 weeks after transplant surgery and compared with 50 healthy control subjects. Continuous, noninvasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 60° head-up tilt and during 1 min of 30% of maximal voluntary handgrip. Plasma and urine catecholamines were assayed, and symptoms were charted.ResultsAt supine rest, heart rate, blood pressures and total peripheral resistance were higher, and stroke volume and end diastolic volume were lower in the HTxR group. During tilt, heart rate, blood pressures and total peripheral resistance increased less, and stroke volume and end diastolic volume decreased less. During handgrip, heart rate and cardiac output increased less, and stroke volume and end diastolic volume decreased less. Orthostatic symptoms were similar across the groups, but the HTxRs complained more of pale and cold hands.ConclusionHTxRs are characterized by elevated blood pressures and total peripheral resistance at supine rest as well as attenuated blood pressures and total peripheral resistance responses during orthostatic challenge, possibly caused by low-pressure cardiopulmonary baroreceptor denervation. In addition, HTxRs show attenuated cardiac output response during isometric exercise due to efferent sympathetic denervation. These physiological limitations might have negative functional consequences.

Abstract 421: Organ-on-chip Model for Investigating Autonomic Innervation of the Cardiac Microenvironment

Cardiac sympathovagal imbalance is a dysfunction of the parasympathetic and sympathetic nervous systems (PSNS and SNS) that, in tandem, regulate cardiac output in response to environmental stimuli. This autonomic nervous system (ANS) imbalance increases the risk of cardiac arrhythmias and sudden cardiac failure due to an inability to modulate heart rate following overexertion or excessive stress. Therefore, there is an immediate need to understand the underlying cellular mechanisms of cardiac innervation to develop new strategies to restore ANS balance. Moving away from the complexity and variability of in vivo models, we developed an in vitro microphysiological model of the cardiac ANS. Custom “cut and assembled” microfluidic organ chips were fabricated to support the 3D culture of cardiac cells and ANS neurons within a biomimetic scaffold. Using this system, on-chip innervation of the cardiac microenvironment was confirmed via immunostaining (Figure 1). Further, we demonstrated trending differences in cardiomyocyte beating between those innervated by each ANS neuron population (PSNS vs. SNS: 37.4 ± 6.7 bpm vs. 44.8 ± 7.9 bpm, n = 8, p = 0.0716) via video microscopy and custom software (MATLAB®). Investigations to alter cardiomyocyte function to promote the innervation of different neural populations within the cardiac microenvironment are ongoing. Specifically, beat rate will be increased/decreased with pharmacological agents and innervation quantified using commercial neuron tracing software (Neurolucida®). Altogether, the development and use of this model will enable the systematic investigation of novel therapies to restore cardiac sympathovagal balance.

Hemodynamic monitoring of ARDS by critical care echocardiography

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in intensive care units and affects about 10% of critically ill patients and almost 25% of mechanically ventilated patients. It is characterized by life-threatening impairment of pulmonary gas exchange, but in two-thirds of cases is associated with hemodynamic instability. Shock is the primary factor influencing mortality and is driven by sepsis in half of the cases and by a more specific mechanism of ARDS in the other half, which is pulmonary vascular dysfunction, i.e., pulmonary hypertension related to the inflammatory process in the lung, which is very sensitive to a respiratory strategy. ARDS-related right ventricular failure, which is also named acute cor pulmonale (ACP), occurs in 20–25% of patients in the area of lung protective ventilation. In this condition, critical care echocardiography (CCE) plays a central role in adequate hemodynamic assessment and management at the bedside because of its ability to yield information quickly on cardiac dimensions and function, respiratory variations of vena cava dimensions and changes in cardiac output in response to therapy. Added to clinical and laboratory data, with invasive blood pressure monitoring and a central venous catheter, such information can be used to define the cause of circulatory failure, to evaluate the benefit and risk balance of fluid expansion, and to consider a strategy for right ventricle protection. Moreover, in the most severe situations, CCE can also guide the establishment and good functioning of extracorporeal membrane oxygenation (ECMO). In this article, we illustrate and summarize the value of CCE in ARDS and give some physiological pointers to its appropriate use.

Sustained Muscle Deoxygenation vs. Sustained High VO2 During High-Intensity Interval Training in Sprint Canoe-Kayak

Recent data suggests that peripheral adaptations, i.e., the muscle ability to extract and use oxygen, may be a stronger predictor of canoe-kayak sprint performance compared to VO2max or central adaptations. If maximizing the time near VO2max during high-intensity interval training (HIIT) sessions is believed to optimize central adaptations, maximizing the time near maximal levels of muscle desaturation could represent a critical stimulus to optimize peripheral adaptations.Purpose: Therefore, the purpose of this study was to assess the VO2, muscle oxygenation and cardiac output responses to various HIIT sessions, and to determine which type of HIIT elicits the lowest muscle oxygenation and the longest cumulated time at low muscle O2 saturation.Methods: Thirteen well-trained canoe-kayak athletes performed an incremental test to determine VO2max and peak power output (PPO), and 4 HIIT sessions (HIIT-15: 40x[15 s at 115%PPO, 15 s at 30%PPO]; HIIT-30: 20x[30 s at 115%PPO, 30 s at 30%PPO]; HIIT-60: 6x[1 min at 130%PPO, 3 min rest]; sprint interval training (SIT): 6x[30 s all-out, 3 min 30 rest]) on a canoe or kayak ergometer. Portable near-infrared spectroscopy monitors were placed on the Latissimus dorsi (LD), Biceps brachii (BB), and Vastus lateralis (VL) during every session to assess changes in muscle O2 saturation (SmO2, % of physiological range).Results: HIIT-15 and HIIT-30 elicited a longer time >90%VO2max (HIIT-15: 8.1 ± 6.2 min, HIIT-30: 6.8 ± 4.6 min), compared to SIT (1.7 ± 1.3 min, p = 0.006 and p = 0.035) but not HIIT-60 (4.1 ± 1.7 min). SIT and HIIT-60 elicited the lowest SmO2 in the VL (SIT: 0 ± 1%, HIIT-60: 8 ± 9%) compared to HIIT-15 (26 ± 12%, p < 0.001 and p = 0.007) and HIIT-30 (25 ± 12%, p < 0.001 and p = 0.030). SIT produced the longest time at >90% of maximal deoxygenation in all 3 muscles, with effect sizes ranging from small to very large.Conclusions: Short HIIT performed on a canoe/kayak ergometer elicits the longest time near VO2max, potentially conducive to VO2max improvements, but SIT is needed in order to maximize muscle deoxygenation during training, which would potentially conduct to greater peripheral adaptations.

Impaired central hemodynamics in chronic obstructive pulmonary disease during submaximal exercise.

It is unknown whether central hemodynamics are impaired during exercise in chronic obstructive pulmonary disease (COPD) patients. We hypothesized that, at a similar absolute V̇o2 during exercise, COPD patients would have a lower stroke volume and cardiac output compared with healthy controls. Furthermore, we hypothesized that greater static hyperinflation [ratio of inspiratory capacity to total lung capacity (IC/TLC)] and expiratory intrathoracic pressure would be significantly related to the lower cardiac output and stroke volume responses in COPD patients. Clinically stable COPD (n = 13; FEV1/FVC: 52 ± 13%) and controls (n = 10) performed constant workload submaximal exercise at an absolute V̇o2 of ~1.3 L/min. During exercise, inspiratory capacity maneuvers were performed to determine operating lung volumes and cardiac output (via open-circuit acetylene rebreathe technique) and esophageal pressure were measured. At similar absolute V̇o2 during exercise (P = 0.81), COPD had lower cardiac output than controls (COPD: 11.0 ± 1.6 vs. control: 12.2 ± 1.2 L/min, P = 0.03) due to a lower stroke volume (COPD: 107 ± 13 vs. control: 119 ± 19 mL, P = 0.04). The heart rate response during exercise was not different between groups (P = 0.66). FEV1 (%predicted) and IC/TLC were positively related to stroke volume (r = 0.68, P = 0.01 and r = 0.77, P < 0.01). Last, esophageal pressure-time integral during inspiration was positively related to cardiac output (r = 0.56, P = 0.047). These data demonstrate that COPD patients have attenuated cardiac output and stroke volume responses during exercise compared with control. Furthermore, these data suggest that the COPD patients with the most severe hyperinflation and more negative inspiratory intrathoracic pressures have the most impaired central hemodynamic responses.NEW & NOTEWORTHY Chronic obstructive pulmonary disease leads to cardiac structural changes and pulmonary derangements that impact the integrative response to exercise. However, it is unknown whether these pathophysiological alterations influence the cardiac response during exercise. Herein, we demonstrate that COPD patients exhibit impaired central hemodynamics during exercise that are worsened with greater hyperinflation.

The Role of Physiology and Voice in Emotion Perception During Social Stress

Deciphering others’ affect is ubiquitous in daily life and is important for navigating social interactions and relationships. Research has found that behavioral components, such as facial expressions or body language, are critical channels by which people understand other people’s affect. In the current research, we examined how people’s perceptions of targets’ positive affect (PA) and negative affect (NA) are associated with targets’ physiological reactivity, and whether behavioral indices mediate these associations. A total of 94 participants (i.e., observers) watched videos of targets completing a social stress task during which targets’ physiological reactivity [i.e., changes in respiratory sinus arrhythmia (RSA), cardiac output (CO), and ventricular contractility (VC)] was assessed. We predicted (1) targets’ RSA reactivity would be negatively associated with observers’ perceptions of PA and NA (to a lesser magnitude than PA); (2) targets’ CO reactivity would be positively associated with observers’ perceptions of PA and unrelated to perceptions of NA; and (3) targets’ VC would be positively associated perceptions of PA or NA (VC was an exploratory hypothesis). Our hypotheses were largely supported. Mediational analyses revealed that vocal prosody was a significant mediator of the association between perceptions of targets’ affect and their physiological reactivity. The findings suggest that observers can reliably detect targets’ emotional experiences as they manifest at a physiological level and that voice is an especially useful marker of how people perceive others’ affective experience. The findings have implications for aspects of relationships involving emotion perception, including affect contagion and interpersonal emotion regulation.

Opportunities and challenges of a novel cardiac output response to stress (CORS) test to enhance diagnosis of heart failure in primary care: a qualitative study

BackgroundPrimary care physicians lack access to an objective cardiac function test during diagnostic testing for suspected heart failure.AimTo determine the role of the novel Cardiac Output Response to Stress (CORS) test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation in primary care.MethodQualitative study using semi-structured in-depth interviews which were audiorecorded and transcribed verbatim. Data from the interviews were analysed thematically using an inductive approach. Fourteen healthcare professionals (six males, eight females) from primary (GPs, nurses, healthcare assistants, and practice managers) and secondary care (consultant cardiologists) participated.ResultsFour themes relating to opportunities and challenges surrounding the implementation of the new diagnostic technology were identified. These reflected that adoption of CORS test would be an advantage to primary care but the test had barriers to implementation which include establishment of clinical utility, suitability for immobile patients, and cost implication to GP practices.ConclusionThe development of a simple non-invasive clinical test to accelerate the diagnosis of heart failure in primary care maybe helpful to reduce unnecessary referrals to secondary care. The CORS test has the potential to serve this purpose however, factors such as cost-effectiveness, diagnostic accuracy, and seamless implementation in primary care have to be fully explored.

Opportunities and challenges of a novel cardiac output response to stress (CORS) test to enhance diagnosis of heart failure in primary care: qualitative study

ObjectiveTo explore the role of the novel cardiac output response to stress (CORS), test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation...

Thick Hearts Can't Keep Up: Exercise Limitations in Patients With Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy (HCM) may experience intolerance to submaximal and maximal exercise. While ejection fraction is generally preserved, reduced left ventricular end diastolic volume may limit stroke volume reserve and potentially attenuate maximal oxygen uptake (V̇O2max). Whether the relationship between supply (cardiac output, Q̇c) and demand (oxygen uptake, V̇O2) remains intact in these patients is unclear.PURPOSETo quantify the cardiac output response to a given metabolic demand during submaximal and maximal exercise in patients with HCM.METHODSEight patients with HCM (45.8±8.8 years, 75% female, left ventricular outflow tract pressure gradient 13±12mmHg) completed two bouts of submaximal steady‐state treadmill exercise (SS1 ~45% and SS2 ~60% V̇O2max), followed by an incremental treadmill test to exhaustion. V̇O2 (Douglas bag technique), Q̇c, (acetylene rebreathing), stroke volume (Q̇c/heart rate) and arterio‐venous difference (av‐O2 diff, Fick principle) were measured during rest, SS1, SS2 and maximal exercise. Stroke volume reserve was calculated as the percent increase in stroke volume from rest to maximal exercise. The relationship between Q̇c and V̇O2 (Q̇c/V̇O2 slope) was quantified using data collected at rest, submaximal and maximal exercise. Healthy sedentary adults (n=8) and subjects with left ventricular hypertrophy from hypertension (LVH, n=8) were included for age and sex‐matched comparison.RESULTSPatients with HCM had lower relative V̇O2max than healthy subjects and patients with LVH (HCM: 21.1±4.8mL/kg/min, healthy: 27.5±3.4 mL/kg/min, LVH 24.4±7.5 mL/kg/ min). The Q̇c response to a given metabolic demand was impaired in patients with HCM when compared to healthy controls and patients with LVH (HCM: 4.6, control: 5.4, LVH: 5.5; Figure 1). The blunted Q̇c/V̇O2 slope was primarily due to a smaller stroke volume reserve (HCM 28.8±27.0%, healthy 52.2±19.6%, LVH 48.6±25.0%), but also a significantly lower maximal heart rate compared to healthy controls (154±24 vs. 178±10 beats per minute, respectively; P&lt;0.05), though 75% of HCM patients were on beta‐blockade and/or calcium channel‐blockade therapy. Remarkably, five HCM patients were able to compensate for a blunted Q̇c/V̇O2 slope (4.2±0.4) and still achieve &gt;80% of predicted V̇O2max by significantly augmenting av‐O2 diff from rest to maximal exercise (Δav‐O2 diff 10.6±1.6 vs. 6.2±1.5 in HCM patients who did not achieve 80% of predicted V̇O2 max, P&lt;0.05).CONCLUSIONAlthough ejection fraction is preserved, patients with HCM may be unable to sufficiently match Q̇c to metabolic demands. However, some patients appear to compensate by significantly augmenting peripheral oxygen extraction and achieve at least 80% of predicted V̇O2max.Support or Funding InformationSupported by The Center for Regenerative Science and Medicine, UTSW Medical Center, Biotronik Inc., and the Research Endowment from The American College of Sports Medicine Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Contribution of Cardiovascular Reserve to Prognostic Categories of Heart Failure With Preserved Ejection Fraction: A Classification Based on Machine Learning

The authors used cluster analysis of data from cardiovascular domains associated with exercise intolerance to help define prognostic phenotypes of patients with heart failure with preserved ejection fraction (HFpEF). Resting and postexercise echocardiography was performed in 177 patients with HFpEF and 51 asymptomatic control subjects sharing a common clinical profile. Patterns of features that determine exercise capacity were sought from automated hierarchical clustering of left ventricular (LV) diastolic and systolic function, left atrial function, right ventricular function, ventricular-arterial coupling, chronotropic reserve and myocardial fibrosis. Automated clustering separated a distinct subgroup characterized by a relatively isolated impairment of LV systolic reserve. The clinical factors identified by this process were used to define two phenotypes of patients with symptomatic HFpEF: those with reduced chronotropic and/or diastolic reserve (abnormal CR/DR; n=137) and those with preserved heart rate reserve and exertional E/e' ratio<14 (normal CR/DR; n=40). Change in global LV strain rate from rest to exercise was similar in patients with abnormal CR/DR (0.16±0.18sec-1) and those with normal CR/DR (0.21±0.17sec-1) and significantly lower than in asymptomatic subjects (0.54±0.20sec-1; P<.001 for all). However, although the former group also showed abnormal longitudinal deformation, ventricular-arterial coupling, and cardiac output responses to exercise, the latter group showed only reduced LV systolic reserve. The normal CR/DR group had a lower incidence of cardiovascular hospitalization or death (P=.003) and heart failure hospitalization (P=.002) than the abnormal CR/DR group during 2-year follow-up. Diminished LV systolic reserve may represent the major identifiable cardiac functional abnormality associated with exercise intolerance in some patients with HFpEF. Despite significant functional limitation, these patients are characterized by a better prognosis than subjects with HFpEF with more physiologic abnormalities.

Maternal Cardiac Output Response to Colloid Preload and Vasopressor Therapy During Spinal Anesthesia for Cesarean Section in Patients With Severe Preeclampsia: A Randomized, Controlled Trial

(Anaesthesia. 2018;73:23–31) Minimally invasive cardiac output monitors have been used in parturients to assess the hemodynamic effects of spinal anesthesia and the commonly used vasopressors phenylephrine and ephedrine. However, studies utilizing these devices have been performed mostly in healthy parturients, with data lacking for those with severe preeclampsia. This randomized study’s objective was to compare the cardiac output response to phenylephrine or ephedrine administered for spinal hypotension during cesarean delivery in women with severe early-onset preeclampsia as well as to measure the stroke volume response to administration of a colloid preload.

Abstract 16737: Cardiopulmonary Fitness and Cardiac Reserve 12-Months Following the Completion of Anthracycline-Based Chemotherapy With or Without Concurrent Exercise Training

Introduction: Anthracycline chemotherapy (AC) has been associated with reductions in cardiac function that increases long-term risk of heart failure. We have previously shown that AC is associated with a reduction in cardiopulmonary fitness (VO 2 peak) that occurs alongside a subtle reduction in the heart’s contractile response to exercise. However the degree to which these changes recover following the completion of AC is unknown. Hypothesis. We sought to determine whether change in cardiopulmonary fitness (VO 2 peak) and cardiac function persisted at 12-months post-AC completion. Methods: 28 women with breast cancer who had self-selected to undergo 12-weeks of aerobic and resistance training twice per week during AC (ET; n=14) or usual care during AC (UC; n=14) were followed up at 12-months from AC completion. Prior to AC and at 12-months, participants completed a cardiopulmonary exercise test (VO 2 peak) and cardiac MRI with exercise to assess the stroke volume (SV), heart rate (HR) and cardiac output (CO) response to exercise (measured at rest, and during high-intensity supine cycling). Results: Seventeen women (UC: n=8; ET: n=9) have completed follow-up evaluation. AC was associated with reductions in fitness at 12-months in both the UC (22.4±6.8 to 19.1±6.9 ml/kg/min; 15%) and ET (28.5±6.0 to 26.5±5.4 ml/kg/min; 6%, P&lt;0.01), and these declines were not attenuated by ET (interaction, P=0.42). Peak CO was reduce by 13% as compared with pre-AC values (14.0 ± 2.5L/min vs 12.2 ± 2.6 L/min, P&lt;0.01). The reduction in CO was due to a 14% reduction in the SV response to exercise (98.3 ± 12.1 ml vs 84.6 ± 14.5 ml, P&lt;0.01), whereas the HR response was similar (146 ± 16 bpm vs 151 ± 17bpm, P=0.70). No differences were found between resting CO and SV from pre-AC to 12-months (P=0.25 and P=0.27 respectively). Conclusion: Cardiopulmonary fitness reductions persisted 12-months following AC-based chemotherapy, which was not attenuated by exercise during AC. Reductions in fitness coincided with reductions in peak cardiac output during exercise.

Prediction of fluid responsiveness in ventilated patients.

Fluid administration is the first-line therapy in patients with acute circulatory failure. The main goal of fluid administration is to increase the cardiac output and ultimately the oxygen delivery. Nevertheless, the decision to administer fluids or not should be carefully considered, since half of critically ill patients are fluid unresponsive, and the deleterious effects of fluid overload clearly documented. Thus, except at the initial phase of hypovolemic or septic shock, where hypovolemia is constant and most of the patients responsive to the initial fluid resuscitation, it is of importance to test fluid responsiveness before administering fluids in critically ill patients. The static markers of cardiac preload cannot reliably predict fluid responsiveness, although they have been used for decades. To address this issue, some dynamic tests have been developed over the past years. All these tests consist in measuring the changes in cardiac output in response to the transient changes in cardiac preload that they induced. Most of these tests are based on the heart-lung interactions. The pulse pressure or stroke volume respiratory variations were first described, following by the respiratory variations of the vena cava diameter or of the internal jugular vein diameter. Nevertheless, all these tests are reliable only under strict conditions limiting their use in many clinical situations. Other tests such as passive leg raising or end-expiratory occlusion act as an internal volume challenge. To reliably predict fluid responsiveness, physicians must choose among these different dynamic tests, depending on their respective limitations and on the cardiac output monitoring technique which is used. In this review, we will summarize the most recent findings regarding the prediction of fluid responsiveness in ventilated patients.

Increased stressor-evoked cardiovascular reactivity is associated with reduced amygdala and hippocampus volume.

Exaggerated cardiovascular reactivity to acute psychological stress is associated with an increased risk of developing cardiovascular disease. The amygdala and hippocampus have been implicated in centrally mediating stressor‐evoked cardiovascular reactivity. However, little is known about the associations of amygdala and hippocampus morphology with stressor‐evoked cardiovascular reactivity. Forty (M age = 19.05, SD = 0.22 years) healthy young women completed two separate testing sessions. Session 1 assessed multiple parameters of cardiovascular physiology at rest and during a validated psychological stress task (Paced Auditory Serial Addition Test), using electrocardiography, Doppler echocardiography, and blood pressure monitoring. In Session 2, 1 year later, structural MRI was conducted. Brain structural volumes were computed using automated segmentation methods. Regression analyses, following Benjamini‐Hochberg correction, showed that greater heart rate and cardiac output reactivity were associated with reduced amygdala and hippocampus gray matter volume. Systolic blood pressure reactivity was associated with reduced hippocampus volume. In contrast, no associations between diastolic blood pressure, mean arterial blood pressure, stroke volume, or total peripheral resistance reactivity with amygdala or hippocampus volumes were apparent. Comparison analyses examining insula volume found no significant associations. Some indicators of greater stressor‐evoked cardiovascular reactivity associate with reduced amygdala and hippocampus gray matter volume, but the mechanisms of this association warrant further study.

β-Blocker therapy for cirrhotic cardiomyopathy: a randomized-controlled trial.

Cirrhotic cardiomyopathy is characterized by an attenuated contractile response to stress. Long-term exposure of β-adrenergic receptors to persistently high levels of catecholamines has been implicated in its pathogenesis. We hypothesized that β-blockade with metoprolol could reverse the changes in heart function and morphology in cirrhotic cardiomyopathy. In this prospective randomized trial, we included 78 patients aged between 18 and 60 years with abnormal cardiac output response under dobutamine stress echocardiography, without primary cardiac disease or a history of alcohol intake. Patients were assigned randomly to receive metoprolol or placebo for 6 months. The primary endpoint was the improvement in cardiac output response to stress, measured by an increase in the left ventricle stroke volume more than 30%. Three (7.3%) patients in the metoprolol group and nine (24.3%) patients in the placebo group showed improved stroke volume (P=0.057). Diastolic dysfunction was found in two (4.8%) patients before and in five (15.6%) patients after therapy in the metoprolol group, and in 10 (27%) patients before and nine (31%) patients after therapy in the placebo group (P=0.67). After treatment, no echocardiography parameter of morphology was significantly different between metoprolol or placebo groups. No significant differences were observed in noradrenaline, plasma renin activity, and troponin levels between groups. Cirrhosis-related clinical events, including hospitalizations and mortality, were not significantly different between the two groups. Six months of therapy with β-blocker did not ameliorate heart function and morphology in patients with cirrhotic cardiomyopathy.