Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

A pilot study to assess the feasibility of a remotely monitored high-intensity interval training program prior to allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Although allogeneic hematopoietic stem cell transplantation (HCT) can be a curative therapy for hematologic disorders, it is associated with treatment-related complications and losses in cardiorespiratory fitness and physical function. High-intensity interval training (HIIT) may be a practical way to rapidly improve cardiorespiratory fitness and physical function in the weeks prior to HCT. The primary aim of this study was to assess the feasibility of implementing a pre-HCT home-based HIIT intervention. The secondary aim was to evaluate pre to post changes in cardiorespiratory fitness and physical function following the intervention. METHODS: This was a single-arm pilot study with patients who were scheduled to undergo allogeneic HCT within six months. Patients were instructed to complete three 30-minute home-based HIIT sessions/week between the time of study enrollment and sign-off for HCT. Sessions consisted of a 5-minute warm-up, 10 high and low intervals performed for one minute each, and a 5-minute cool-down. Prescribed target heart rates (HR) for the high- and low-intensity intervals were 80-90% and 50-60% of HR reserve, respectively. Heart rates during HIIT were captured via an Apple Watch and were remotely monitored. Feasibility was assessed via retention, session adherence, and adherence to prescribed interval number and intensities. Paired t-tests were used to compare changes in fitness (VO2peak) and physical function [Short Physical Performance Battery (SPPB), 30-second sit to stand, and six-minute walk test (6MWT)] between baseline and sign-off. Pearson correlations were used to determine the relationship between intervention length and changes in cardiorespiratory fitness or functional measures. RESULTS: Thirteen patients (58.8±11.6 years) participated in the study, and nine (69.2%) recorded their training sessions throughout the study. Median session adherence for those nine participants was 100% (IQR: 87-107). Adherence to intervals was 92% and participants met or exceeded prescribed high-intensity HR on 68.8±34.8% of intervals. VO2peak improved from baseline to sign-off (14.6±3.1 mL/kg/min to 17.9±3.3 mL/kg/min; p<0.001). 30-second sit to stand and SPPB chair stand scores significantly improved in adherent participants. Improvements in 30-second sit to stand (13.8±1.5 to 18.3±3.3 seconds) and 6MWT (514.4±43.2 to 564.6±19.3) exceeded minimal clinically important improvements established in other chronic disease populations, representing the minimum improvement considered meaningful to patients. CONCLUSIONS: Findings demonstrate that implementing a pre-HCT home-based remotely monitored HIIT program is feasible and may provide benefits to cardiorespiratory fitness and physical function.

The utility of a portable muscle ultrasound in the assessment of muscle alterations in children with acute lymphoblastic leukaemia.

BACKGROUND: During treatment for acute lymphoblastic leukaemia (ALL), children are prone to musculoskeletal deterioration. However, non-invasive tools to measure muscle mass and intramuscular alterations are limited. In this study we explored the feasibility of muscle ultrasound in children with ALL. Additionally, we analysed whether automated ultrasound outcomes of muscle size and intramuscular fat infiltration (IMAT) were associated with appendicular skeletal muscle mass (ASMM), muscle strength and physical performance. METHODS: Children with ALL, aged 3-18 years were included during maintenance therapy. Bilateral images of the rectus femoris muscle were captured using a portable linear array transducer connected to a tablet. Subsequently, an automated image annotation software (MuscleSound) was used to estimate cross-sectional area, muscle thickness and IMAT. Feasibility was assessed using acceptance (percentage of children approached who were enrolled), practicality (percentage of children that completed the ultrasound measurement after enrolment) and implementation (percentage of children that had sufficient imaging to be processed and analysed by the software). Assessments of ASMM by bioimpedance analysis, muscle strength using handheld dynamometry and timed physical performance tests were administered at the same visit. Multivariable linear models were estimated to study the associations between muscle ultrasound outcomes and ASMM, strength and physical performance, adjusted for sex, age, body mass index and ALL treatment week. RESULTS: Muscle ultrasound was performed in 60 out of 73 invited patients (76.9%), of which 37 were boys (61.7%), and median age was 6.1 years (range: 3-18.8 years). The acceptance was 98.7%, practicality 77.9% and implementation was 100%. Patients who refused the examination (n = 13) were younger (median: 3.6, range: 3-11.2 years) compared with the 60 examined children (P = 0.0009). In multivariable models, cross-sectional area was associated with ASMM (ß = 0.49 Z-score, 95% confidence interval [CI]:0.3,2.4), knee-extension strength (ß = 16.9 Newton [N], 95% CI: 4.8, 28.9), walking performance (ß = -0.46 s, 95% CI: -0.75, -0.18) and rising from the floor (ß = -1.07 s, 95% CI: -1.71, -0.42). Muscle thickness was associated with ASMM (ß = 0.14 Z-score, 95% CI: 0.04, 0.24), knee-extension strength (ß = 4.73 N, 95% CI: 0.99, 8.47), walking performance (ß = -0.13 s, 95% CI: -0.22, -0.04) and rising from the floor (ß = -0.28 s, 95% CI: -0.48, -0.08). IMAT was associated with knee-extension strength (ß = -6.84 N, 95% CI: -12.26, -1.41), walking performance (ß = 0.2 s, 95% CI: 0.08, 0.32) and rising from the floor (ß = 0.54 s, 95% CI: 0.27, 0.8). None of the muscle ultrasound outcomes was associated with handgrip strength. CONCLUSIONS: Portable muscle ultrasound appears a feasible and useful tool to measure muscle size and intramuscular alterations in children with ALL. Validation studies using magnetic resonance imaging (gold standard) are necessary to confirm accuracy in paediatric populations.

Splanchnic Nerve Modulation Effects on Surrogate Measures of Venous Capacitance.

Background Splanchnic nerve modulation (SNM) is an emerging procedure to reduce cardiac filling pressures in heart failure. Although the main contributor to reduction in cardiac preload is thought to be increased venous capacitance in the splanchnic circulation, supporting evidence is limited. We examined changes in venous capacitance surrogates pre- and post-SNM. Methods and Results This is a prespecified analysis of a prospective, open-label, single-arm interventional study evaluating the effects of percutaneous SNM with ropivacaine in chronic heart failure with elevated filling pressures at rest and with exercise. Patients underwent cardiopulmonary exercise testing with invasive hemodynamic assessment pre- and post-SNM. Blood pressure changes with modified Valsalva maneuver and hemoconcentration, pre- and post-SNM were compared using a repeated measures model. Inferior vena cava diameter and collapsibility (>50% decrease in size with inspiration), and presence of bendopnea pre- and post-SNM were also compared. Fifteen patients undergoing SNM (age 58 years, 47% women, 93% with left ventricular ejection fraction ≤35%) were included. After SNM, changes in systolic blood pressure during Valsalva (peak-to-trough) were greater (41 versus 48 mm Hg, P=0.025). Exercise-induced hemoconcentration was unchanged (0.63 versus 0.43 g/dL, P=0.115). Inferior vena cava diameter was reduced (1.59 versus 1.30 cm, P=0.034) with higher collapsibility (33% versus 73%, P=0.014). Bendopnea was less (47% versus 13%, P=0.025). Conclusions SNM resulted in increased venous capacitance, associated decreased cardiac preload, and decreased bendopnea. Minimally invasive measures of venous capacitance could serve as markers of successful SNM. Long-term effects of SNM on venous capacitance warrant further investigation for heart failure management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03453151.

Clinical Utility of the Cardiorespiratory Optimal Point in Patients with Heart Failure.

INTRODUCTION: We assessed the cardiorespiratory optimal point (COP)-the minimal V̇E /V̇O 2 in a given minute of an incremental cardiopulmonary exercise test-in patients with heart failure (HF) and aimed to determine 1) its association with patient and disease characteristics, 2) changes after an exercise-based cardiac rehabilitation program (CR), and 3) the association with clinical outcomes. METHODS: We studied 277 HF patients (67 (58-74) yr, 30% female, 72% HF with restricted ejection fraction) between 2009 and 2018. Patients participated in a 12- to 24-wk CR program, and COP was assessed pre- and post-CR. Patient and disease characteristics and clinical outcomes (mortality and cardiovascular-related hospitalization) were extracted from patient files. The incidence of clinical outcomes was compared across COP tertiles (low, <26.0; moderate, 26.0-30.7; high, >30.7). RESULTS: Median COP was 28.2 (24.9-32.1) and was reached at 51% ± 15% of V̇O 2peak . Lower age, female sex, higher body mass index, the absence of a pacemaker or the absence of chronic obstructive pulmonary disease, and lower N-terminal prohormone brain natriuretic peptide concentrations were associated with a lower COP. Participation in CR reduced COP (-0.8; 95% confidence interval, -1.3 to -0.3). Low COP had a reduced risk (adjusted hazard ratio, 0.53; 95% confidence interval, 0.33-0.84) for adverse clinical outcomes as compared with high COP. CONCLUSIONS: Classic cardiovascular risk factors are associated with a higher, more unfavorable, COP. CR-based exercise training reduces COP, whereas a lower COP is associated with a better clinical prognosis. As COP can be established during a submaximal exercise test, this may offer novel risk stratification possibilities for HF care programs.

No association between thickening fraction of the diaphragm and extubation success in ventilated children.

Introduction: In mechanically ventilated adults, thickening fraction of diaphragm (dTF) measured by ultrasound is used to predict extubation success. Whether dTF can also predict extubation success in children is unclear. Aim: To investigate the association between dTF and extubation success in children. Second, to assess diaphragm thickness during ventilation and the correlation between dTF, diaphragm thickness (Tdi), age and body surface. Method: Prospective observational cohort study in children aged 0-18 years old with expected invasive ventilation for >48 h. Ultrasound was performed on day 1 after intubation (baseline), day 4, day 7, day 10, at pre-extubation, and within 24 h after extubation. Primary outcome was the association between dTF pre-extubation and extubation success. Secondary outcome measures were Tdi end-inspiratory and Tdi end-expiratory and atrophy defined as <10% decrease of Tdi end-expiratory versus baseline at pre-extubation. Correlations were calculated with Spearman correlation coefficients. Inter-rater reliability was calculated with intraclass correlation (ICC). Results: Fifty-three patients, with median age 3.0 months (IQR 0.1-66.0) and median duration of invasive ventilation of 114.0 h (IQR 55.5-193.5), were enrolled. Median dTF before extubation with Pressure Support 10 above 5 cmH2O was 15.2% (IQR 9.7-19.3). Extubation failure occurred in six children, three of whom were re-intubated and three then received non-invasive ventilation. There was no significant association between dTF and extubation success; OR 0.33 (95% CI; 0.06-1.86). Diaphragmatic atrophy was observed in 17/53 cases, in three of extubation failure occurred. Children in the extubation failure group were younger: 2.0 months (IQR 0.81-183.0) vs. 3.0 months (IQR 0.10-48.0); p = 0.045. At baseline, pre-extubation and post-extubation there was no significant correlation between age and BSA on the one hand and dTF, Tdi- insp and Tdi-exp on the other hand. The ICC representing the level of inter-rater reliability between the two examiners performing the ultrasounds was 0.994 (95% CI 0.970-0.999). The ICC of the inter-rater reliability between the raters in 36 paired assessments was 0.983 (95% CI 0.974-0.990). Conclusion: There was no significant association between thickening fraction of the diaphragm and extubation success in ventilated children.

Blood Pressure Variability in Clinical Practice: Past, Present and the Future.

Recent advances in wearable technology through convenient and cuffless systems will enable continuous, noninvasive monitoring of blood pressure (BP), heart rate, and heart rhythm on both longitudinal 24-hour measurement scales and high-frequency beat-to-beat BP variability and synchronous heart rate variability and changes in underlying heart rhythm. Clinically, BP variability is classified into 4 main types on the basis of the duration of monitoring time: very-short-term (beat to beat), short-term (within 24 hours), medium-term (within days), and long-term (over months and years). BP variability is a strong risk factor for cardiovascular diseases, chronic kidney disease, cognitive decline, and mental illness. The diagnostic and therapeutic value of measuring and controlling BP variability may offer critical targets in addition to lowering mean BP in hypertensive populations.

Reference values of diaphragmatic dimensions in healthy children aged 0-8 years.

Diaphragmatic thickness (Tdi) and diaphragm thickening fraction (dTF) are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children are scarce. We determined reference values of Tdi and dTF using ultrasound in healthy children aged 0-8 years old and assessed their reproducibility. In a prospective, observational cohort, Tdi and dTF were measured on ultrasound images across four age groups comprising at least 30 children per group: group 1 (0-6 months), group 2 (7 months-1 year), group 3 (2-4 years) and group 4 (5-8 years). Ultrasound images of 137 healthy children were included. Mean Tdi at inspiration was 2.07 (SD 0.40), 2.09 (SD 0.40), 1.69 (SD 0.30) and 1.72 (SD 0.30) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at expiration was 1.64 (SD 0.30), 1.67 (SD 0.30), 1.38 (SD 0.20) and 1.42 (SD 0.20) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at inspiration and mean Tdi at expiration for groups 1 and 2 were significantly greater than those for groups 3 and 4 (both p < 0.001). Mean dTF was 25.4% (SD 10.4), 25.2% (SD 8.3), 22.8% (SD 10.9) and 21.3% (SD 7.1) for group 1, 2, 3 and 4, respectively. The intraclass correlation coefficients (ICC) representing the level of inter-rater reliability between two examiners performing the ultrasounds was 0.996 (95% CI 0.982-0.999). ICC of the inter-rater reliability between the raters in 11 paired assessments was 0.989 (95% CI 0.973-0.995).   Conclusion: Ultrasound measurements of Tdi and dTF were highly reproducible in healthy children aged 0-8 years.    Trial registration: ClinicalTrials.gov identifier (NCT number): NCT04589910. What is Known: • Diaphragmatic thickness and diaphragm thickening fraction are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children to compare these with are scarce. What is New: • We determined normal values of diaphragmatic thickness and diaphragm thickening fraction using ultrasound in 137 healthy children aged 0-8 years old. The diaphragmatic thickness of infants up to 1 year old was significantly greater than that of children from 2 to 8 years old. Diaphragmatic thickness decreased with an increase in body surface area. These normal values in healthy children can be used to assess changes in respiratory muscle thickness in mechanically ventilated children.

Diaphragmatic Function in Cardiovascular Disease: JACC Review Topic of the Week.

In addition to the diaphragm's role as the primary respiratory muscle, it also plays an under-recognized role in cardiac function. It serves as a pump facilitating venous and lymph return, modulating left ventricular afterload hemodynamics and pericardial pressures, as well as regulating autonomic tone. Heart failure (HF) is associated with diaphragmatic changes (ie, muscle fiber atrophy and weakness, increased ratio of type I to type II muscle fibers, and altered muscle metaboreflex) that lead to diaphragmatic dysfunction with subsequent symptomatic manifestations of HF. Herein, it is proposed that targeting the diaphragm in patients with HF via inspiratory muscle training or device-based stimulation can provide a novel treatment pathway for HF. Reviewed are several potential mechanisms through which therapies targeting the diaphragm can be beneficial in HF (ie, improving preload reserve, atrial and ventricular synchrony, and metaboreflex activity; reducing pericardial restraint; and restoring diaphragm strength).

Advances in muscle health and nutrition: A toolkit for healthcare professionals.

Low muscle mass and malnutrition are prevalent conditions among adults of all ages, with any body weight or body mass index, and with acute or chronic conditions, including COVID-19. This article synthesizes the latest research advancements in muscle health and malnutrition, and their impact on immune function, and clinical outcomes. We provide a toolkit of illustrations and scientific information that healthcare professionals can use for knowledge translation, educating patients about the importance of identifying and treating low muscle mass and malnutrition. We focus on the emerging evidence of mitochondrial dysfunction in the context of aging and disease, as well as the cross-talk between skeletal muscle and the immune system. We address the importance of myosteatosis as a component of muscle composition, and discuss direct, indirect and surrogate assessments of muscle mass including ultrasound, computerized tomography, deuterated creatine dilution, and calf circumference. Assessments of muscle function are also included (handgrip strength, and physical performance tests). Finally, we address nutrition interventions to support anabolism, reduce catabolism, and improve patient outcomes. These include protein and amino acids, branched-chain amino acids, with a focus on leucine; ß-hydroxy-ß-methylbutyrate (HMB), vitamin D; n-3 polyunsaturated fatty acids (n-3 PUFA), polyphenols, and oral nutritional supplements. We concluded with recommendations for clinical practice and a call for action on research focusing on evaluating the impact of body composition assessments on targeted nutrition interventions, and consequently their ability to improve patient outcomes.

Automated versus manual analysis of body composition measures on computed tomography in patients with bladder cancer.

PURPOSE: Manual measurement of body composition on computed tomography (CT) is time-consuming, limiting its clinical use. We validate a software program, Automatic Body composition Analyzer using Computed tomography image Segmentation (ABACS), for the automated measurement of body composition by comparing its performance to manual segmentation in a cohort of patients with bladder cancer. METHOD: We performed a retrospective analysis of 285 patients treated for bladder cancer at the Duke University Health System from 1996 to 2017. Abdominal CT images were manually segmented at L3 using Slice-O-Matic. Automated segmentation was performed with ABACS on the same L3-level images. Measures of interest were skeletal muscle (SM) area, subcutaneous adipose tissue (SAT) area, and visceral adipose tissue (VAT) area. SM index, SAT index, and VAT index were calculated by dividing component areas by patient height2 (m2). Patients were dichotomized as sarcopenic, having excessive subcutaneous fat, or having excessive visceral fat using published cut-off values. Agreement between manual and automated segmentation was assessed using the Pearson product-moment correlation coefficient (PPMCC), the interclass correlation coefficient (ICC3), and the kappa statistic (κ). RESULTS: There was strong agreement between manual and automatic segmentation, with PPMCCs > 0.90 and ICC3s > 0.90 for SM, SAT, and VAT areas. Categorization of patients as sarcopenic (κ = 0.73), having excessive subcutaneous fat (κ = 0.88), or having excessive visceral fat (κ = 0.90) displayed high agreement between methods. CONCLUSIONS: Automated segmentation of body composition measures on CT using ABACS performs similarly to manual analysis and may expedite data collection in body composition research.

Quantitative Blood Volume Analysis and Hemodynamic Measures of Vascular Compliance in Patients With Worsening Heart Failure.

BACKGROUND: The role of blood volume (BV) expansion vs a change in vascular compliance in worsening heart failure (HF) remains under debate. We aimed to assess the relationship between BV and resting and stress hemodynamics in worsening HF and to further elucidate the significance of BV in cardiac decompensation. METHODS AND RESULTS: Patients with worsening HF underwent radiolabeled indicator-dilution BV analysis and cardiac catheterization. Intravascular volumes and resting/stress hemodynamics were recorded. Provocative stress maneuvers included change in systolic blood pressure (ΔSBP) from lying to standing and Valsalva and intracardiac pressure changes with leg raise. Correlation between BV and invasive hemodynamics were assessed by linear regression. Of 27 patients with worsening HF, patients' characteristics included mean age 61 ± 12 years, 70% male, 19% Black, and mean ejection fraction 29% ± 15%. Of the patients, 13 (48%) had hypervolemia as measured by total BV, which weakly correlated with ΔSBP by position (R2 = 0.009) and Valsalva (R2 = 0.003) and with right atrial (R2 = 0.049) and pulmonary capillary wedge (R2 = 0.047) pressure changes during leg raise. CONCLUSIONS: In patients with worsening HF, BV mildly correlated with intracardiac pressures at rest. Provocative maneuvers intended to test vascular compliance did not correlate with BV, indicating that compliance may serve as a stand-alone metric in HF.

Pericardial Adipose Tissue Volume and Left Ventricular Assist Device-Associated Outcomes.

BACKGROUND: Pericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing left ventricular assist device (LVAD) implantation. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes. METHODS AND RESULTS: We retrospectively measured computed tomography-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015 and March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219 cm3) and below-median (<219 cm3) PAT volume. Those with above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease and ischemic cardiomyopathy. Groups with above-median vs below-median PAT had similar Kaplan-Meier incidence rates over 2 years for (1) composite all-cause mortality, redo-LVAD surgery and cardiac transplantation (35.9 vs 32.2%; log-rank P = 0.65) and (2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs 60.5%; log-rank P = 0.67). CONCLUSIONS: In patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse 2-year LVAD-related outcomes. The significance of regional adiposity vs obesity in LVAD patients warrants further investigation.

Nonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction) is not well established. Methods and Results This was a retrospective, cohort study among Medicare beneficiaries. We selected Medicare beneficiaries without known prior diagnosis of HF. NAFLD was defined using presence of 1 inpatient or 2 outpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), claims codes. Incident HF was defined using at least 1 inpatient or at least 2 outpatient HF claims during the follow-up period (October 2015-December 2016). Among 870 535 Medicare patients, 3.2% (N=27 919) had a clinical diagnosis of NAFLD. Patients with NAFLD were more commonly women, were less commonly Black patients, and had a higher burden of comorbidities, such as diabetes, obesity, and kidney disease. Over a mean 14.3 months of follow-up, patients with (versus without) baseline NAFLD had a significantly higher risk of new-onset HF in unadjusted (6.4% versus 5.0%; P<0.001) and adjusted (adjusted hazard ratio [HR] [95% CI], 1.23 [1.18-1.29]) analyses. Among HF subtypes, the association of NAFLD with downstream risk of HF was stronger for HF with preserved ejection fraction (adjusted HR [95% CI], 1.24 [1.14-1.34]) compared with HF with reduced ejection fraction (adjusted HR [95% CI], 1.09 [0.98-1.2]). Conclusions Patients with NAFLD are at an increased risk of incident HF, with a higher risk of developing HF with preserved ejection fraction versus HF with reduced ejection fraction. The persistence of an increased risk after adjustment for clinical and demographic factors suggests an epidemiological link between NAFLD and HF beyond the basis of shared risk factors that requires further investigation.

Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations.

BACKGROUND & AIMS: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic demands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations. METHODS: This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition - Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients. RESULTS: The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic mREE at 21.3 kcal/kg/d or 110% of predicted by the HB equation over the first week of mechanical ventilation (MV). This progressed to significant and uniquely prolonged hypermetabolism over successive weeks to 28.1 kcal/kg/d or 143% of HB predicted by MV week 3, with hypermetabolism persisting to MV week 7. Obese individuals displayed a more truncated response with significantly lower mREE versus non-obese patients in MV week 1 (19.5 ± 1.0 kcal/kg/d vs 25.1 ± 1.8 kcal/kg/d, respectively; p < 0.01), with little change in weeks 2-3 (19.5 ± 1.5 kcal/kg/d vs 28.0 ± 2.0 kcal/kg/d; p < 0.01). Both ASPEN-SCCM upper range and PSU pREE equations provided close approximations of mREE yet, like all pREE equations, occasionally over- and under-predicted energy needs and typically did not predict late hypermetabolism. CONCLUSIONS: Study results show a truly unique metabolic response in COVID-19 ICU patients, characterized by significant and prolonged, progressive hypermetabolism peaking at 3 weeks' post-intubation, persisting for up to 7 weeks in ICU. This pattern was more clearly demonstrated in non-obese versus obese patients. This response is unique and distinct from any previously described model of ICU stress response in its prolonged hypermetabolic nature. This data reaffirms the need for routine, longitudinal IC measures to provide accurate energy targets in COVID-19 ICU patients. The PSU and ASPEN-SCCM equations appear to yield the most reasonable estimation to IC-derived mREE in COVID-19 ICU patients, yet still often over-/under-predict energy needs. These findings provide a practical guide for caloric prescription in COVID-19 ICU patients in the absence of IC.

Monitoring muscle mass using ultrasound: a key role in critical care.

PURPOSE OF REVIEW: The loss of muscle mass in critically ill patients contributes to morbidity and mortality, and results in impaired recovery of physical functioning. The number of publications on the topic is increasing. However, there is a lack of consistent methodology and the most optimal methodology remains unclear, hampering its broad use in clinical practice. RECENT FINDINGS: There is a large variety of studies recently published on the use of ultrasound for assessment of muscle mass. A selection of studies has been made, focusing on monitoring of muscle mass (repeated measurements), practical aspects, feasibility and possible nutrition and physical therapy interventions. In this review, 14 new small (n = 19-121) studies are categorized and reviewed as individual studies. SUMMARY: The use of ultrasound in clinical practice is feasible for monitoring muscle mass in critically ill patients. Assessment of muscle mass by ultrasound is clinically relevant and adds value for guiding therapeutic interventions, such as nutritional and physical therapy interventions to maintain muscle mass and promote recovery in critically ill patients.

Splanchnic nerve modulation in heart failure: mechanistic overview, initial clinical experience, and safety considerations.

Volume recruitment from the splanchnic compartment is an important physiological response to stressors such as physical activity and blood loss. In the setting of heart failure (HF), excess fluid redistribution from this compartment leads to increased cardiac filling pressures with limitation in exercise capacity. Recent evidence suggests that blocking neural activity of the greater splanchnic nerve (GSN) could have significant benefits in some patients with HF by reducing cardiac filling pressures and improving exercise capacity. However, to date the long-term safety of splanchnic nerve modulation (SNM) in the setting of HF is unknown. SNM is currently used in clinical practice to alleviate some forms of chronic abdominal pain. A systematic review of the series where permanent SNM was used as a treatment for chronic abdominal pain indicates that permanent SNM is well tolerated, with side-effects limited to transient diarrhoea or abdominal colic and transient hypotension. The pathophysiological role of the GSN in volume redistribution, the encouraging findings of acute and chronic pilot SNM studies and the safety profile from permanent SNM for pain provides a strong basis for continued efforts to study this therapeutic target in HF.

Point-Counterpoint: Indirect Calorimetry Is Essential for Optimal Nutrition Therapy in the Intensive Care Unit.

Iatrogenic malnutrition and underfeeding are ubiquitous in intensive care units (ICUs) worldwide for prolonged periods after ICU admission. A major driver leading to the lack of emphasis on timely ICU nutrition delivery is lack of objective data to guide nutrition care. If we are to ultimately overcome current fundamental challenges to effective ICU nutrition delivery, we must all adopt routine objective, longitudinal measurement of energy targets via indirect calorimetry (IC). Key evidence supporting the routine use of IC in the ICU includes (1) universal societal ICU nutrition guidelines recommending IC to determine energy requirements; (2) data showing predictive equations or body weight calculations that are consistently inaccurate and correlate poorly with measured energy expenditure, ultimately leading to routine overfeeding and underfeeding, which are both associated with poor ICU outcomes; (3) recent development and worldwide availability of a new validated, accurate, easy-to-use IC device; and (4) recent data in ICU patients with coronavirus disease 2019 (COVID-19) showing progressive hypermetabolism throughout ICU stay, emphasizing the inaccuracy of predictive equations and marked day-to-day variability in nutrition needs. Thus, given the availability of a new validated IC device, these findings emphasize that routine longitudinal IC measures should be considered the new standard of care for ICU and post-ICU nutrition delivery. As we would not deliver vasopressors without accurate blood pressure measurements, the ICU community is only likely to embrace an increased focus on the importance of early nutrition delivery when we can consistently provide objective IC measures to ensure personalized nutrition care delivers the right nutrition dose, in the right patient, at the right time to optimize clinical outcomes.

The physiological effect of early pregnancy on a woman's response to a submaximal cardiopulmonary exercise test.

Given all its systemic adaptive requirements, pregnancy shares several features with physical exercise. In this pilot study, we aimed to assess the physiological response to submaximal cardiopulmonary exercise testing (CPET) in early pregnancy. In 20 healthy, pregnant women (<13 weeks gestation) and 20 healthy, non-pregnant women, we performed a CPET with stationary cycling during a RAMP protocol until 70% of the estimated maximum heart rate (HR) of each participant. Hemodynamic and respiratory parameters were non-invasively monitored by impedance cardiography (PhysioFlow® ) and a breath-by-breath analyzer (OxyconTM ). To compare both groups, we used linear regression analysis, adjusted for age. We observed a similar response of stroke volume, cardiac output (CO) and HR to stationary cycling in pregnant and non-pregnant women, but a slightly lower 1-min recovery rate of CO (-3.9 [-5.5;-2.3] vs. -6.6 [-8.2;-5.1] L min-1  min-1 ; p = .058) and HR (-38 [-47; -28] vs. -53 [-62; -44] bpm/min; p = .065) in pregnant women. We also observed a larger increase in ventilation before the ventilatory threshold (+6.2 [5.4; 7.0] vs. +3.2 [2.4; 3.9] L min-1  min-1 ; p < .001), lower PET CO2 values at the ventilatory threshold (33 [31; 34] vs. 36 [34; 38] mmHg; p = .042) and a larger increase of breathing frequency after the ventilatory threshold (+4.6 [2.8; 6.4] vs. +0.6 [-1.1; 2.3] breaths min-1  min-1 ; p = .015) in pregnant women. In conclusion, we observed a slower hemodynamic recovery and an increased ventilatory response to exercise in early pregnancy.