A Clinical and Physiological Prospective Observational Study on the Management of Pediatric Shock in the Post-Fluid Expansion as Supportive Therapy Trial Era.

OBJECTIVES: Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy. DESIGN: We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints. SETTING: Pediatric wards of Mbale Regional Referral Hospital, Uganda, and Kilifi County Hospital, Kenya, conducted between October 2013 and July 2015. Data were analysed from August 2016 to July 2019. PATIENTS: Children (≥ 60 d to ≤ 12 yr) with severe febrile illness and clinical signs of impaired perfusion. INTERVENTIONS: IV maintenance fluid (4 mL/kg/hr) unless children had World Health Organization (WHO) defined shock (≥ 3 signs) where they received two fluid boluses (20 mL/kg) and transfusion if shock persisted. Clinical, electrocardiographic, echocardiographic, and laboratory data were collected at presentation, during resuscitation and on day 28. Outcome measures were 48-hour mortality, normalization of hemodynamics, and cardiac biomarkers. MEASUREMENT AND MAIN RESULTS: Thirty children (70% males) were recruited, six had WHO shock, all of whom died (6/6) versus three of 24 deaths in the non-WHO shock. Median fluid volume received by survivors and nonsurvivors were similar (13 [interquartile range (IQR), 9-32] vs 30 mL/kg [28-61 mL/kg], z = 1.62, p = 0.23). By 24 hours, we observed increases in median (IQR) stroke volume index (39 mL/m 2 [32-42 mL/m 2 ] to 47 mL/m 2 [41-49 mL/m 2 ]) and a measure of systolic function: fractional shortening from 30 (27-33) to 34 (31-38) from baseline including children managed with no-bolus. Children with WHO shock had a higher mean level of cardiac troponin ( t = 3.58; 95% CI, 1.24-1.43; p = 0.02) and alpha-atrial natriuretic peptide ( t = 16.5; 95% CI, 2.80-67.5; p < 0.01) at admission compared with non-WHO shock. Elevated troponin (> 0.1 µg/mL) and hyperlactatemia (> 4 mmol/L) were putative makers predicting outcome. CONCLUSIONS: Maintenance-only fluid therapy normalized clinical and myocardial perturbations in shock without compromising cardiac or hemodynamic function whereas fluid-bolus management of WHO shock resulted in high fatality. Troponin and lactate biomarkers of cardiac dysfunction could be promising outcome predictors in pediatric septic shock in resource-limited settings.

Advantage and validation of vendor-independent software for myocardial strain analysis compared to vendor-specific software.

INTRODUCTION: One of the main limitations incorporating strain imaging into widespread clinical practice is inter-vendor incompatibility. This poses a problem when serial strain measurements are required in a multi-vendor echocardiography laboratory. METHODS: This study sought to compare the variability of two-dimensional speckle-tracking global and regional longitudinal strain using vendor-specific software and vendor-independent software from images acquired by two different commercially available ultrasound systems. Forty subjects underwent two sequential echocardiographic acquisitions using different ultrasound systems (GE Vivid E9 and Philips iE33). Global longitudinal strain and regional peak longitudinal strain were derived using vendor-specific software (EchoPAC BT 13 v201 and QLAB version 10.3) and vendor-independent software (TomTec Image Arena version 4.6). Agreement and reproducibility of global and regional strain between vendor-specific and vendor-independent software were assessed by independent blinded observers. RESULTS: Global longitudinal strain derived from vendor-independent software was comparable to global longitudinal strain derived from vendor-specific software, whilst regional strain was lower in agreement compared to global longitudinal strain. There was good overall agreement and high inter- and intra-observer reproducibility using vendor-independent software for global longitudinal strain and regional strain. CONCLUSIONS: Vendor-independent software provides good agreement with vendor-specific software for global longitudinal strain. However, minor variability exists for regional strain measurements between vendor-independent and vendor-specific software. Good agreement of strain measurements derived by vendor-independent software suggests vendor-independent software could potentially be useful for serial follow-up of global longitudinal strain.

Association of computed tomography-derived myocardial mass with fractional flow reserve-verified ischemia or subsequent therapeutic strategy.

The aim of the present study was to examine the association of myocardial mass verified by computed tomography (CT) and invasive fractional flow reserve (FFR)-verified myocardial ischemia, or subsequent therapeutic strategy for the targeted vessels after FFR examination. We examined 333 vessels with intermediate stenoses in 297 patients (mean age 69.0 ± 9.5, 228 men) undergoing both coronary CT angiography and invasive FFR, and reviewed the therapeutic strategy after FFR. Of 333 vessels, FFR ≤ 0.80 was documented in 130 (39.0%). Myocardial volume supplied by the target vessel (MVT) was larger in those with FFR-verified ischemia than those without (53.4 ± 19.5 vs. 42.9 ± 22.2 cm3, P < 0.001). Addition of MVT to a model including patient characteristics (age, gender), visual assessment (≥ 70% stenosis, high-risk appearance), and quantitative CT vessel parameters [minimal lumen area (MLA), plaque burden at MLA, percent aggregate plaque volume] improved C-index (from 0.745 to 0.778, P = 0.020). Furthermore, of 130 vessels with FFR ≤ 0.80, myocardial volume exposed to ischemia (MVI) was larger in the vessels with early revascularization after FFR examination than those without (37.2 ± 20.0 vs. 26.8 ± 15.0 cm3, P = 0.003), and was independently associated with early revascularization [OR = 1.03, 95% confidence interval (1.02-1.11), P < 0.001]. Using an on-site CT workstation, MVT identified coronary arteries with FFR-verified ischemia easily and non-invasively, and MVI was associated with subsequent therapeutic strategy after FFR examinations.

Cardiac perturbations after high-intensity exercise are attenuated in middle-aged compared with young endurance athletes: diminished stress or depleted stimuli?

Strenuous exercise elicits transient functional and biochemical cardiac imbalances. Yet, the extent to which these responses are altered owing to aging is unclear. Accordingly, echocardiograph-derived left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) and high-sensitivity cardiac troponin I (hs-cTnI) were assessed before (pre) and after (post) a 60-min high-intensity cycling race intervention (CRIT60) in 11 young (18-30 yr) and 11 middle-aged (40-65 yr) highly trained male cyclists, matched for cardiorespiratory fitness. LV and RV GLS were measured at rest and during a semirecumbent exercise challenge performed at the same intensity (young: 93 ± 10; middle-aged: 85 ± 11 W, P = 0.60) pre- and post-CRIT60. Augmentation (change from rest-to-exercise challenge) of LV GLS (pre: -2.97 ± 0.65; post: -0.82 ± 0.48%, P = 0.02) and RV GLS (pre: -2.08 ± 1.28; post: 3.08 ± 2.02%, P = 0.01) was attenuated and completely abolished, in the young following CRIT60, while augmentation of LV GLS (pre: -3.21 ± 0.41; post: -3.99 ± 0.55%, P = 0.22) and RV GLS (pre: -3.47 ± 1.44; post: -1.26 ± 1.00%, P = 0.27) was preserved in middle-aged following CRIT60. While serum hs-cTnI concentration increased followingCRIT60 in the young (pre: 7.3 ± 1.6; post: 17.7 ± 1.6 ng/L, P < 0.01) and middle-aged (pre: 4.5 ± 0.6; post: 10.7 ± 2.0 ng/L, P < 0.01), serum hs-cTnI concentration increased to a greater extent in the young than in the middle-aged following CRIT60 (P < 0.01). These findings suggest that functional and biochemical cardiac perturbations induced by high-intensity exercise are attenuated in middle-aged relative to young individuals. Further study is warranted to determine whether acute exercise-induced cardiac perturbations alter the adaptive myocardial remodeling response.NEW & NOTEWORTHY High-intensity endurance exercise elicits acute cardiac imbalances that may be an important stimulus for adaptive cardiac remodeling. This study highlights that following a bout of high-intensity exercise that is typical of routine day-to-day cycling training, exercise-induced autonomic, biochemical, and functional cardiac imbalances are attenuated in middle-aged relative to young well-trained cyclists. These findings suggest that aging may alter exercise-induced stress stimulus response that initiates cardiac remodeling in athlete's heart.

Marked Disparity in Regional and Transmural Cardiac Mechanics in the Athlete's Heart.

INTRODUCTION: Regional heterogeneity of the human heart plays an important role in left ventricular (LV) and right ventricular (RV) function and may contribute to enhanced myocardial efficiency in the athlete's heart. PURPOSE: This study comprehensively characterized regional and transmural myocardial tissue deformation (strain) in recreationally active (RA) and endurance-trained (ET) men to determine if regional nonuniformity evolves alongside morphological adaptations associated with endurance training. METHODS: Echocardiography was used to measure LV and RV global, regional (apical, mid, basal) and transmural (endocardial, epicardial) longitudinal strain in 30 endurance-trained (ET) (age, 31 ± 2 yr; body mass index, 23.1 ± 0.5 kg·m; V˙O2peak, 60.2 ± 6.5 mL·kg·min) and 30 RA (age: 29 ± 2 yr; body mass index, 23.4 ± 0.4 kg·m; V˙O2peak: 42.6 ± 4.6 mL·kg·min). Nonuniformity was characterized using apex-to-base and transmural (endocardial-to-epicardial) strain gradients. RESULTS: Global longitudinal strain was similar in ET and RA in the left (-17.4% ± 0.4% vs -17.8% ± 0.5%, P = 0.662) and right ventricle (-25.8% ± 0.8% vs 26.4% ± 1.0%, P = 0.717). The apex-to-base strain gradient was greater in ET than RA in the left (-6.5% ± 0.7% vs -2.7% ± 0.8%, P = 0.001) and right ventricle (-9.6% ± 1.8% vs -3.0% ± 1.6%, P = 0.010). The LV transmural strain gradient was greater than RV in both groups, but similar in ET and RA (-4.7% ± 0.2% vs -4.7% ± 0.2%, P = 0.850), whereas RV transmural strain gradient was greater in ET than RA (-3.4% ± 0.3% vs -1.6% ± 0.4%, P = 0.003). RV apex-to-base and transmural strain gradients correlated with RV end-diastolic area (R = 0.536 & 0.555, respectively, P < 0.01) and V˙O2peak (R = 0.415 & 0.677, respectively, P < 0.01). CONCLUSIONS: Transmural nonuniformity is more pronounced in the left ventricle than the RV free wall; however, RV functional nonuniformity develops markedly after endurance training. Differences in myocardial architecture and exercise-induced wall stress in the left and right ventricles are possible explanations for the marked functional nonuniformity throughout the myocardium and in response to endurance exercise training.

Diastolic strain imaging: a new non-invasive tool to detect subclinical myocardial dysfunction in early cardiac allograft rejection.

Acute cellular rejection (ACR) remains a significant contributor to increased morbidity and mortality in heart transplant recipients. Early detection of ACR by non-invasive imaging is of potential clinical benefit. This study sought to investigate the use of non-invasive early global diastolic strain rate (GDSRe) and global longitudinal strain (GLS) in the detection of biopsy proven ACR. We retrospectively analysed 31 heart transplant patients (Mean age 52 ± 14 years) with biopsy proven ACR who underwent serial transthoracic echocardiographic examination and 2D strain analysis. Traditional echocardiographic systolic and diastolic parameters and novel systolic and diastolic strain imaging were measured during (1) early rejection free period (0R); (2) pre-rejection period (pre-1R); and (3) grade 1R acute cellular rejection (1R-ACR). GDSRe was significantly reduced (p = 0.0001) during the pre-rejection period (pre-1R) (0.74/s) when compared with 0R (0.97/s). GLS was only significantly reduced during 1R-ACR (17.7%), p = 0.001 but could not detect pre-1R (19.9%). Global diastolic strain rate at isovolumic relaxation showed no significant differences between any of the rejection periods. Traditional systolic and diastolic indices showed no significant differences. In conclusion, early global diastolic strain rate is the most sensitive parameter to detect subclinical myocardial dysfunction during early periods of pre-1R prior to biopsy confirmed 1R-ACR. GDSRe is a potential new tool for non-invasive screening of early post-transplant cardiac allograft rejection.

Global Myocardial Work Is Superior to Global Longitudinal Strain to Predict Significant Coronary Artery Disease in Patients With Normal Left Ventricular Function and Wall Motion.

BACKGROUND: Noninvasive detection of functionally significant coronary artery disease (CAD) by echocardiography remains challenging, with the need to perform stress imaging to detect ischemia. The aim of this study was to determine whether global myocardial work (MW), derived from noninvasive left ventricular (LV) pressure-strain loops at rest, can predict significant CAD in patients without regional wall motion abnormalities and preserved LV ejection fraction (EF). METHODS: One hundred and fifteen patients referred for coronary angiography who had EF ≥ 55%, no resting regional wall motion abnormalities, and no chest pain were assessed using echocardiography. Global MW was derived from noninvasive LV pressure-strain loops constructed from speckle-tracking echocardiography indexed to brachial systolic blood pressure. Global constructive work represented the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation. Global wasted work represented energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation. Global MW efficiency was derived from the percentage ratio of constructive work to the sum of constructive work and wasted work. RESULTS: Patients with significant CAD demonstrated a significantly reduced global MW (P < .001) compared with those without CAD. Global longitudinal strain was significantly reduced (P < .001) in patients with multivessel CAD but not those with single-vessel CAD (P = .47). Receiver operating characteristic curve analysis demonstrated that global MW was the most powerful predictor of significant CAD (area under the curve = 0.786) and was superior to global longitudinal strain (area under the curve = 0.693). The optimal cutoff global MW value to predict significant CAD was 1,810 mm Hg% (sensitivity, 92%; specificity, 51%). CONCLUSIONS: Noninvasive global MW derived using LV pressure-strain loops at rest is a more sensitive index than global longitudinal strain to detect significant CAD in patients with no regional wall motion abnormalities and normal EF. This is a potential valuable clinical tool to assist in the early diagnosis of CAD.

Echocardiographic assessment of myocardial function and mechanics during veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Transthoracic echocardiography (TTE) plays a fundamental role in the management of patients supported with extra-corporeal membrane oxygenation (ECMO). In light of fluctuating clinical states, serial monitoring of cardiac function is required. Formal quantification of ventricular parameters and myocardial mechanics offer benefit over qualitative assessment. The aim of this research was to compare unenhanced (UE) versus contrast-enhanced (CE) quantification of myocardial function and mechanics during ECMO in a validated ovine model. METHODS: Twenty-four sheep were commenced on peripheral veno-venous ECMO. Acute smoke-induced lung injury was induced in 21 sheep (3 controls). CE-TTE with Definity using Cadence Pulse Sequencing was performed. Two readers performed image analysis with TomTec Arena. End diastolic area (EDA, cm2), end systolic area (ESA, cm2), fractional area change (FAC, %), endocardial global circumferential strain (EGCS, %), myocardial global circumferential strain (MGCS, %), endocardial rotation (ER, degrees) and global radial strain (GRD, %) were evaluated for UE-TTE and CE-TTE. RESULTS: Full data sets are available in 22 sheep (92%). Mean CE EDA and ESA were significantly larger than in unenhanced images. Mean FAC was almost identical between the two techniques. There was no significant difference between UE and CE EGCS, MGCS and ER. There was significant difference in GRS between imaging techniques. Unenhanced inter-observer variability was from 0.48-0.70 but significantly improved to 0.71-0.89 for contrast imaging in all echocardiographic parameters. CONCLUSION: Semi-automated methods of myocardial function and mechanics using CE-TTE during ECMO was feasible and similar to UE-TTE for all parameters except ventricular areas and global radial strain. Addition of contrast significantly decreased inter-observer variability of all measurements.

Reproducibility of global left atrial strain and strain rate between novice and expert using multi-vendor analysis software.

Left atrial (LA) strain is an emerging technique with potential applications including arrhythmia prediction in atrial fibrillation and early identification of atrial dysfunction. The aim of this study was to evaluate reproducibility of LA strain and strain rate (SR) using multi-vendor analysis software between novice and expert. For LA strain to be a reliable tool, the technique must be reproducible by observers with variable experience. Use of multi-vendor analysis software allows serial strain assessment when echocardiographic images are acquired using different vendors. Fifty subjects underwent 2D-Speckle tracking echocardiographic (STE) derived LA strain and SR analysis measured from apical four and two-chamber views. Three strain parameters of LA function were assessed: reservoir (S-LAs, SR-LAs), contractile (S-LAa, SR-LAa) and conduit (S-LAs-S-LAa, SR-LAe). Strain analyses were performed by 2 independent, blinded novice and expert observers using multi-vendor analysis software. Intraobserver and interobserver analyses were performed using intra class correlation coefficients (ICC) and Bland-Altman analysis. LA strain and SR measured by novice observer demonstrated excellent intraobserver reproducibility (ICC for all strain and SR values > 0.88). There was good interobserver agreement of LA strain values between novice and expert (S-LAs:ICC 0.81, S-LAe:ICC 0.82, S-LAa:ICC 0.74). SR values also demonstrated good interobserver agreement (SR-LAs:ICC 0.83, SR-LAe:ICC 0.79, SR-LAa:ICC 0.86). Of all parameters, SR-LAa had the best interobserver and intraobserver agreement (ICC 0.86, 0.96). Global LA strain and SR values were highly reproducible by novice strain reader using multi-vendor analysis software. Interobserver reproducibility between novice and experts were good and acceptable within limits of agreement.

A new approach to assess myocardial work by non-invasive left ventricular pressure-strain relations in hypertension and dilated cardiomyopathy.

Aims: Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages over conventional global longitudinal strain (GLS) by incorporating measurements of myocardial deformation and LV pressure. We investigated different patterns of LV PSL and global MW index (GWI) in patients with hypertension (HTN) and dilated cardiomyopathy (CMP). Methods and results: Seventy-four patients underwent transthoracic echocardiography and strain analysis before coronary angiography. Patients were divided into three groups: control, HTN, and CMP. GWI was calculated as the area of the LV PSL as a product of strain × systolic blood pressure. MW efficiency (GWE) is derived from the percentage ratio of constructive work (GCW) to sum of constructive work (GCW) and wasted work (GWW). Influences of HTN and LV function on its relationship with MW were evaluated. GLS and LV ejection fraction were preserved in the HTN group with no difference from controls. GWI was significantly higher in moderate to severe HTN patients (P = 0.004) as a compensatory mechanism to preserve LV contractility and function against an increase in afterload. GWE was preserved in HTN patients due to the proportional increase in GCW and GWW. GLS, GWI, and GWE were significantly reduced in CMP (P < 0.05), with a trend in rightward shift and reduction in the LV PSL. Conclusion: GWI is a potential new technique that allows better understanding of the relationship between LV remodelling and increased wall stress under different loading conditions.

Early Changes of Myocardial Function After Transcatheter Aortic Valve Implantation Using Multilayer Strain Speckle Tracking Echocardiography.

Transcatheter aortic valve implantation (TAVI) is an effective therapeutic option for severe symptomatic aortic valve stenosis (AS) with intermediate or high surgical risk. The purpose of this study was to examine the effects of TAVI on left ventricular (LV) mechanics using multilayer global longitudinal strain (GLS) by 2D speckle-tracking echocardiography. A total of 119 patients (mean age 83 ± 7.0 years, male 54%) with severe symptomatic AS and normal LV ejection fraction (LVEF) underwent echocardiography at baseline and 1 month after TAVI. Global longitudinal strain was measured from the endocardial layer (GLSendo), mid-ventricular layer (GLSmyo), epicardial layer (GLSepi) and full thickness of myocardium (GLSwhole). There was significant improvement in all 3 layers of GLS after TAVI compared with baseline, but there was no significant change in LVEF. The relative % increment in GLS in each layer strain were 11.2 ± 23.4% (GLSendo), 13.4 ± 33.0% (GLSmyo) and 18.0 ± 46.6% (GLSepi) with significant difference between GLSendo and GLSepi (p < 0.05). In conclusion, multilayer GLS is more sensitive than conventional LVEF to detect early improvement in LV systolic function after TAVI in patients with severe AS. There is a disproportional improvement in different layers with least improvement in the endocardium. Multilayer strain analysis may provide new insights into understanding mechanics of AS.

Folic acid supplementation improves vascular endothelial function, yet not skin blood flow during exercise in the heat, in patients with heart failure.

Heart failure (HF) patients are susceptible to heat strain during exercise, secondary to blunted skin blood flow (SkBF) responses, which may be explained by impaired nitric oxide (NO)-dependent vasodilation. Folic acid improves vascular endothelial function and SkBF through NO-dependent mechanisms in healthy older individuals and patients with cardiovascular disease. We examined the effect of folic acid supplementation (5 mg/day for 6 wk) on vascular function [brachial artery flow-mediated dilation (FMD)] and SkBF responses [cutaneous vascular conductance (CVC)] during 60 min of exercise at a fixed metabolic heat production (300 WHprod) in a 30°C environment in 10 patients with HF (New York Heart Association Class I-II) and 10 healthy controls (CON). Serum folic acid concentration increased in HF [preintervention (pre): 1.4 ± 0.2; postintervention (post): 8.9 ± 6.7 ng/ml, P = 0.01] and CON (pre: 1.3 ± 0.6; post: 5.2 ± 4.9 ng/ml, P = 0.03). FMD improved by 2.1 ± 1.3% in HF ( P < 0.01), but no change was observed in CON postintervention ( P = 0.20). During exercise, the external workload performed on the cycle ergometer to attain the fixed level of heat production for exercise was similar between groups (HF: 60 ± 13; CON: 65 ± 20 external workload, P = 0.52). Increases in CVC during exercise were similar in HF (pre: 0.89 ± 0.43; post: 0.83 ± 0.45 au/mmHg, P = 0.80) and CON (pre: 2.01 ± 0.79; post: 2.03 ± 0.72 au/mmHg, P = 0.73), although the values were consistently lower in HF for both pre- and postintervention measurement intervals ( P < 0.05). These findings demonstrate that folic acid improves vascular endothelial function in patients with HF but does not enhance SkBF during exercise at a fixed metabolic heat production in a warm environment.

Extracorporeal Shock Wave Therapy for Coronary Artery Disease: Relationship of Symptom Amelioration and Ischemia Improvement.

OBJECTIVES: The current management of coronary artery disease (CAD) relies on three major therapeutic options, namely medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). However, severe CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW) therapy reported on human for the first time. This treatment resulted in better myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy, angina symptoms, and exercise tolerance. The aim of the present study was to investigate: myocardial perfusion images and evaluate the relationship between the ischemia improvement and symptom amelioration by SW therapy. METHODS: We treated ten patients (i.e., nine males and one female) with cardiac SW therapy who had CAD but not indicated for PCI or CABG and aged 63-89 years old. After the SW therapy, all patients were followed up for three months to evaluate any amelioration of the myocardial ischemia based on symptoms, adenosine stress thallium scintigraphy, transthoracic echocardiography, and blood biochemical examinations. RESULTS: The changes in various parameters were evaluated before and after cardiac SW therapy. The cardiac SW therapy resulted in a significant improvement in the symptoms as evaluated by the Canadian Cardiovascular Society [CCS] class score (P=0.016) and a tendency to improve in summed stress score (SSS) (P=0.068). However, no significant improvement was observed in the summed rest score (SRS), summed difference score (SDS), left ventricular wall motion score index (LVWMSI), N-terminal pro-brain natriuretic, and troponin I. The difference of CCS class score (ΔCCS) was significantly correlated with those of SSS (ΔSSS) and SDS (ΔSDS) (r=0.69, P=0.028 and r=0.70, P=0.025, respectively). There was no significant correlation between ΔCCS and other parameters. Furthermore, no significant difference was observed between the CCS improved and non-improved groups in terms of the baseline characteristics. CONCLUSION: The current study demonstrated the potential efficacy and safety of Cardiac SW therapy in CAD patients. As the findings indicated, symptom amelioration was associated with ischemia improvement by extracorporeal shock wave therapy for the CAD patients.

Thermoeffector Responses at a Fixed Rate of Heat Production in Heart Failure Patients.

PURPOSE: Heart failure (HF) patients seem to exhibit altered thermoregulatory responses during exercise in the heat. However, the extent to which these responses are altered due to physiological impairments independently of biophysical factors associated with differences in metabolic heat production (Hprod), evaporative heat balance requirements (Ereq), and/or body size is presently unclear. Therefore, we examined thermoregulatory responses in 10 HF patients and 10 age-matched controls (CON) similar in body size during exercise at a fixed rate of Hprod and therefore Ereq in a 30°C environment. METHODS: Rectal temperature, local sweat rate, and cutaneous vascular conductance were measured throughout 60 min of cycle ergometry. Whole-body sweat rate was estimated from pre-post nude body weight corrected for fluid intake. RESULTS: Despite exercising at the same rate of Hprod (HF, 338 ± 43 W; CON, 323 ± 31 W; P = 0.25), the rise in rectal temperature was greater (P < 0.01) in HF (0.81°C ± 0.16°C) than in CON (0.49°C ± 0.27°C). In keeping with a similar Ereq (HF, 285 ± 40 W; CON, 274 ± 28 W; P = 0.35), no differences in whole-body sweat rate (HF, 0.45 ± 0.11 L·h; CON, 0.41 ± 0.07 L·h; P = 0.38) or local sweat rate (HF, 0.96 ± 0.17 mg·cm·min; CON, 0.79 ± 0.15 mg·cm·min; P = 0.50) were observed between groups. However, the rise in cutaneous vascular conductance was lower in HF than in CON (HF, 0.83 ± 0.42 au·mm Hg; CON, 2.10 ± 0.79 au·mm Hg; P < 0.01). In addition, the cumulative body heat storage estimated from partitional calorimetry was similar between groups (HF, 154 ± 106 kJ; CON, 196 ± 174 kJ; P = 0.44). CONCLUSIONS: Collectively, these findings demonstrate that HF patients exhibit a blunted skin blood flow response, but no differences in sweating. Given that HF patients had similar body heat storage to that of CON at the same Hprod, their greater rise in core temperature can be attributed to a less uniform internal distribution of heat between the body core and periphery.

Left Ventricular Global Strain Analysis by Two-Dimensional Speckle-Tracking Echocardiography: The Learning Curve.

BACKGROUND: The application of left ventricular (LV) global strain by speckle-tracking is becoming more widespread, with the potential for incorporation into routine clinical echocardiography in selected patients. There are no guidelines or recommendations for the training requirements to achieve competency. The aim of this study was to determine the learning curve for global strain analysis and determine the number of studies that are required for independent reporting. METHODS: Three groups of novice observers (cardiology fellows, cardiac sonographers, medical students) received the same standardized training module prior to undertaking retrospective global strain analysis on 100 patients over a period of 3 months. To assess the effect of learning, quartiles of 25 patients were read successively by each blinded observer, and the results were compared to expert for correlation. RESULTS: Global longitudinal strain (GLS) had uniform learning curves and was the easiest to learn, requiring a minimum of 50 patients to achieve expert competency (intraclass correlation coefficient > 0.9) in all three groups over a period of 3 months. Prior background knowledge in echocardiography is an influential factor affecting the learning for interobserver reproducibility and time efficiency. Short-axis strain analysis using global circumferential stain and global radial strain did not yield a comprehensive learning curve, and expert level was not achieved by the end of the study. CONCLUSIONS: There is a significant learning curve associated with LV strain analysis. We recommend a minimum of 50 studies for training to achieve competency in GLS analysis.

Myocardial and haemodynamic responses to two fluid regimens in African children with severe malnutrition and hypovolaemic shock (AFRIM study).

BACKGROUND: Fluid therapy in severely malnourished children is hypothesized to be deleterious owing to compromised cardiac function. We evaluated World Health Organization (WHO) fluid resuscitation guidelines for hypovolaemic shock using myocardial and haemodynamic function and safety endpoints. METHODS: A prospective observational study of two sequential fluid management strategies was conducted at two East African hospitals. Eligible participants were severely malnourished children, aged 6-60 months, with hypovolaemic shock secondary to gastroenteritis. Group 1 received up to two boluses of 15 ml/kg/h of Ringer's lactate (RL) prior to rehydration as per WHO guidelines. Group 2 received rehydration only (10 ml/kg/h of RL) up to a maximum of 5 h. Comprehensive clinical, haemodynamic and echocardiographic data were collected from admission to day 28. RESULTS: Twenty children were enrolled (11 in group 1 and 9 in group 2), including 15 children (75%) with kwashiorkor, 8 (40%) with elevated brain natriuretic peptide >300 pg/ml, and 9 (45%) with markedly elevated median systemic vascular resistance index (SVRI) >1600 dscm-5/m2 indicative of severe hypovolaemia. Echocardiographic evidence of fluid-responsiveness (FR) was heterogeneous in group 1, with both increased and decreased stroke volume and myocardial fractional shortening. In group 2, these variables were more homogenous and typical of FR. Median SVRI marginally decreased post fluid administration (both groups) but remained high at 24 h. Mortality at 48 h and to day 28, respectively, was 36% (4 deaths) and 81.8% (9 deaths) in group 1 and 44% (4 deaths) and 55.6% (5 deaths) in group 2. We observed no pulmonary oedema or congestive cardiac failure on or during admission; most deaths were unrelated to fluid interventions or echocardiographic findings of response to fluids. CONCLUSION: Baseline and cardiac response to fluid resuscitation do not indicate an effect of compromised cardiac function on response to fluid loading or that fluid overload is common in severely malnourished children with hypovolaemic shock. Endocrine response to shock and persistently high SVRI post fluid-therapy resuscitation may indicate a need for further research investigating enhanced fluid volumes to adequately correct volume deficit. The adverse outcomes are concerning, but appear to be unrelated to immediate fluid management.

Intervendor consistency and reproducibility of left ventricular 2D global and regional strain with two different high-end ultrasound systems.

AIMS: We aimed to assess intervendor agreement of global (GLS) and regional longitudinal strain by vendor-specific software after EACVI/ASE Industry Task Force Standardization Initiatives for Deformation Imaging. METHODS AND RESULTS: Fifty-five patients underwent prospective dataset acquisitions on the same day by the same operator using two commercially available cardiac ultrasound systems (GE Vivid E9 and Philips iE33). GLS and regional peak longitudinal strain were analyzed offline using corresponding vendor-specific software (EchoPAC BT13 and QLAB version 10.3). Absolute mean GLS measurements were similar between the two vendors (GE -17.5 ± 5.2% vs. Philips -18.9 ± 5.1%, P = 0.15). There was excellent intervendor correlation of GLS by the same observer [r = 0.94, P < 0.0001; bias -1.3%, 95% CI limits of agreement (LOA) -4.8 to 2.2%). Intervendor comparison for regional longitudinal strain by coronary artery territories distribution were: LAD: r = 0.85, P < 0.0001; bias 0.5%, LOA -5.3 to 6.4%; RCA: r = 0.88, P < 0.0001; bias -2.4%, LOA -8.6 to 3.7%; LCX: r = 0.76, P < 0.0001; bias -5.3%, LOA -10.6 to 2.0%. Intervendor comparison for regional longitudinal strain by LV levels were: basal: r = 0.86, P < 0.0001; bias -3.6%, LOA -9.9 to 2.0%; mid: r = 0.90, P < 0.0001; bias -2.6%, LOA -7.8 to 2.6%; apical: r = 0.74; P < 0.0001; bias -1.3%, LOA -9.4 to 6.8%. CONCLUSIONS: Intervendor agreement in GLS and regional strain measurements have significantly improved after the EACVI/ASE Task Force Strain Standardization Initiatives. However, significant wide LOA still exist, especially for regional strain measurements, which remains relevant when considering vendor-specific software for serial measurements.

Impact of high-intensity endurance exercise on regional left and right ventricular myocardial mechanics.

AIMS: Strenuous endurance exercise acutely increases myocardial wall stress and evokes transient functional cardiac perturbations. However, it is unclear whether exercise-induced functional cardiac disturbances are ubiquitous throughout the myocardium or are segment specific. The aim of this study was to examine the influence of high-intensity endurance exercise on global and segmental left (LV) and right (RV) ventricular tissue deformation (strain). METHODS AND RESULTS: Echocardiography was used to measure strain in 23 active men (age: 28 ± 2 years; VO2 peak: 4.5 ± 0.7 L min-1) at rest and during a standardized low-intensity exercise challenge, before and after a 90-min high-intensity endurance cycling intervention. Following the cycling intervention, LV and RV global strain decreased at rest (LV: -18.4 ± 0.4% vs. -17.7 ± 0.4%, P < 0.05; RV: -27.6 ± 0.7% vs. -26.4 ± 0.6%, P < 0.05) and by a greater extent during the low-intensity exercise challenge (LV: -21.3 ± 0.4% vs. -19.2 ± 0.5%, P < 0.01; RV: -28.4 ± 0.8% vs. -23.5 ± 0.9%, P < 0.01). Reductions in LV strain were unique to regions of RV attachment (e.g. LV septum: -24.4 ± 0.5% vs. -21.4 ± 0.6%, P < 0.01) with lateral (-18.9 ± 0.4% vs. -18.4 ± 0.5%) and posterior segments (-19.5 ± 0.4% vs. -18.8 ± 0.7%) unaffected. Similarly, augmentation of strain from rest to exercise was abolished in the RV free wall (-1.1 ± 1.0% vs. 2.9 ± 1.2%, P < 0.01), reduced in the septum (-4.6 ± 0.4% vs. -2.4 ± 0.5%, P < 0.01), and unchanged in the lateral (-1.2 ± 0.6% vs. -0.9 ± 0.6%) and posterior walls (-1.7 ± 0.6% vs. -1.3 ± 0.7%). CONCLUSION: Changes in ventricular strain following high-intensity exercise are more profound in the right ventricle than in the left ventricle. Reductions in LV strain were unique to the septal myocardium and may reflect ventricular interactions secondary to exercise-induced RV dysfunction.

Altitude-Induced Pulmonary Hypertension on One-Day Rapid Ascent of Mount Fuji: Incidence and Therapeutic Effects of Sildenafil.

AIMS: Exposure to high altitudes especially with rapid ascent may induce hypoxic pulmonary vasoconstriction (HPV) and pulmonary hypertension (PH) possibly leading to life-threatening high-altitude pulmonary edema (HAPE). The aim of the study was to evaluate the incidence of PH on a 1-day rapid ascent up Mount Fuji (3775 m) in recreational climbers and also to determine the effectiveness of sildenafil for this rapid ascent-induced PH as measured by echocardiography. METHODS AND RESULTS: Twenty-five subjects who climbed Mount Fuji showed significantly increased pulmonary artery systolic pressure (PASP) from 22.3 ± 5.3 mmHg at sea level to 29.4 ± 8.7 mmHg at 3775 m. Five subjects showed PASP >35 mmHg (35.6-46.2 mmHg, average 42.0 ± 3.9 mmHg) and took oral sildenafil 50 mg after which PASP decreased significantly to 24.5 ± 4.6 mmHg (18.7-31.0 mmHg) after 30 minutes. CONCLUSIONS: One-day rapid ascent of Mount Fuji may induce mild-to-moderate PH and intervention with sildenafil can reduce this PH, suggesting that the therapeutic use of sildenafil would be more reasonable for the relatively infrequent occurrence of altitude-induced PH than its prophylactic use.

Usefulness of right ventricular basal free wall strain by two-dimensional speckle tracking echocardiography in patients with chronic thromboembolic pulmonary hypertension.

Recently two-dimensional (2D) speckle tracking echocardiography (STE) derived from right ventricular (RV) free wall has been shown to be a very useful tool for the estimation of RV performance. The purpose of this study was to examine whether RV basal free wall strain can detect increased mean pulmonary arterial pressure (mPAP) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We investigated a total of 126 patients with CTEPH (mean age, 56 ± 12 years). They underwent echocardiography and right heart catheter examination. 2D STE-derived longitudinal strain was measured by placing 2 regions of interests (ROIs) on the RV basal free wall in RV-focused apical 4-chamber view. Peak strain (RV-PS) was acquired between the 2 ROIs. Conventional echocardiographic RV parameters (RV fractional area change, RV myocardial performance index, tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity, and tricuspid regurgitant pressure gradient) were evaluated as well. Right heart catheterization was performed on the day following of echocardiographic evaluation. Among RV echo parameters, RV-PS showed the best correlation with mPAP (r = 0.75, P < 0.0001). Receiver operating characteristic analysis revealed that a cut-off value of RV-PS -20.8% could detect mPAP ≧ 25 mmHg (sensitivity 78%, specificity 93%, area under the curve 0.90, P < 0.001). RV basal free wall strain was a useful tool for the non-invasive detection of increased mPAP in patients with CTEPH.