Differential effect of head-up tilt on cardiovagal and sympathetic baroreflex sensitivity in humans

The purpose of this study was to determine the effect of baroreceptor unloading on the sensitivity of the cardiovagal and sympathetic arms of the baroreflex during upright posture. Beat-by-beat R-R interval, arterial blood pressure and cardiac output (Doppler ultrasound), as well as muscle sympathetic nerve activity (MSNA) were recorded during periods in supine (Supine) and 60 deg head-up tilt (HUT) positions (n = 8 volunteers). Cardiovagal baroreflex sensitivity (BRS) was measured by the spontaneous sequence analysis method using systolic blood pressure and R-R interval, while sympathetic BRS was determined using the slope of the linear relationship between decreasing segments of diastolic blood pressure (DBP) and corresponding increases in MSNA. On changing to HUT, mean R-R interval and cardiac output decreased, while mean measures of MSNA, DBP and total peripheral resistance increased (P < 0.05). Cardiovagal BRS decreased from Supine to 60 deg HUT (19 +/- 2 ms mmHg(-1) versus 7.6 +/- 1.2 ms mmHg(-1); P < 0.01). In contrast, sympathetic BRS increased from -6.1 +/- 1.4 a.u. mmHg(-1) in Supine to -14 +/- 2 a.u. mmHg(-1) in HUT (P < 0.01). Thus, HUT produced differential effects on cardiac versus sympathetic BRS. The data suggest that dynamic baroreflex-mediated cardiovascular control is dominated by sympathetic control during baroreceptor unloading.     

Effect of posture on arterial baroreflex control of heart rate in humans

Summary Altered baroreflex function may contribute to the cardiovascular changes associated with weightlessness. Since central blood volume (CBV) increases during simulated weightlessness, we have examined the possibility that acute changes in CBV may modify baroreceptor function. We used graded head-up tilt (HUT) and head-down tilt (HDT) to induce changes in CBV, and neck suction to stimulte carotid baroreceptors, in 6 subjects. The increase in pulse interval induced by a negative pressure of 8.2 kPa (62 mm Hg) imposed for 10 s while supine was compared with the increase while tilted for 8 min at ± 15, ± 30 and ± 45. During HDT at 15 the pulse interval over the first 5 cardiac cycles following suction onset was 51 ± (SEM) 18 ms longer (p<0.05), at 30 it was 61±20 ms longer (p<0.05), and at 45 it was 74±35 ms longer (p<0.01), compared with supine. During HUT at 15 the pulse interval was 25±9 ms shorter (p<0.05) than when supine, but was not significantly different at 30 and 45. These responses occurred independently of changes in brachial blood pressure. Attenuation was also observed after 5 min (56±17 ms; <0.05), and after 40 min (25±9 ms; p<0.05) of 60 HUT compared with supine. We conclude that posture does modify arterial baroreflex control of heart rate. If this occurs primarily as a result of a change in CBV, then the acute effect of weightlessness may be an accentuation, not an attenuation, of baroreflex function.M. H. Harrison was a National Research Council postdoctoral research fellow on leave from the Ministry of Defence, UK     

Effect of lower-body positive pressure on postural fluid shifts in men

Summary To quantify the effect of 60 mm Hg lower-body positive pressure (LBPP) on orthostatic blood-volume shifts, the mass densities (±0.1 g· l^–1) of antecubital venous blood and plasma were measured in five men (27–42 years) during combined tilt table/antigravity suit inflation and deflation experiments. The densities of erythrocytes, whole-body blood, and of the shifted fluid were computed and the magnitude of fluid and protein shifts were calculated during head-up tilt (60°) with and without application of LBPP. During 30-min head-up tilt with LBPP, blood density (BD) and plasma density (PD) increased by 1.6±0.3 g · l^–1, and by 0.8±0.2 g · l^–1 (±SD) (N=9), respectively. In the subsequent period of tilt without LBPP, BD and PD increased further to +3.6±0.9 g · l^–1, and to +2.0±0.7 g · l^–1 (N=7) compared to supine control. The density increases in both periods were significant (p<0.05). Erythrocyte density remained unaltered with changes in body position and pressure suit inflation/deflation. Calculated shifted-fluid densities (FD) during tilt with LBPP (1006.0±1.1 g · l^–1,N=9), and for subsequent tilt after deflation (1002.8±4.1 g · l^–1,N=7) were different from each other (p<0.03). The plasma volume decreased by 6.0±1.2% in the tilt-LBPP period, and by an additional 6.4±2.7% of the supine control level in the subsequent postdeflation tilt period. The corresponding blood volume changes were 3.7±0.7% (p<0.01), and 3.5±2.1% (p<0.05), respectively. Thus, about half of the postural hemoconcentration occurring during passive head-up tilt was prevented by application of 60 mm Hg LBPP.H. Hinghofer-Szalkay was a European Space Agency fellow on leave from the Physiological Institute, Karl-Franzens-University, A-8010 Graz, Austria.     

Hemodynamic Follow-Up in Adult Patients with Pulmonary Hypertension Associated with Atrial Septal Defect after Partial Closure

PurposeWe evaluated the hemodynamic statuses of patients after partial closure of atrial septal defects with fenestration due to pulmonary hypertension.ResultsThe median age at closure was 29 years old. The baseline Qp/Qs was 1.9±0.6. The median interval from the operation to the cardiac catheterization was 27 months. The CT ratio decreased from 0.55±0.07 to 0.48±0.06 (p<0.05). The mean pulmonary arterial pressure decreased from 50.0±11.5 mm Hg to 32.5±14.4 mm Hg (p<0.05), and the pulmonary resistance index decreased from 9.2±3.6 Wood units^*m² to 6.3±3.8 Wood units^*m² (p<0.05). Eleven patients (64.7%) continued to exhibit high pulmonary resistance (over 3.0 Wood units^*m²) after closure. These patients had significantly higher pulmonary resistance indices and mean pulmonary arterial pressures based on oxygen testing before the partial closures (p<0.05). However, no significant predictors of post-closure pulmonary hypertension were identified.ConclusionDespite improvement in symptoms and hemodynamics after partial closure of an atrial septal defect, pulmonary hypertension should be monitored carefully.     

The behaviour of the flow‐mediated brachial artery vasodilatation during orthostatic stress in normal man

Aims: Flow‐mediated brachial artery vasodilatation is an index of endothelial function. Published literature describes only supine data and no study has been performed during vertical displacement. This subject deserves investigation for two main reasons: humans spend the larger part of their life in the upright position; this position has significant effects on neural vascular regulation. Methods: In 21 healthy men (25 ± 2 years) the flow‐dependent brachial artery vasodilating response to distal circulatory arrest was assessed by Doppler ultrasound imaging, while supine and during 20° and 60° head‐up tilting (HUT). In 11 of these subjects the vasodilating response to nitroglycerine was also explored. Results: Absolute and percentage increments in brachial calibre during hyperaemia after deflation of the occluding cuff became increasingly greater at 20° (+0.44 mm) and 60° (+0.92 mm) HUT (P < 0.01), compared with the horizontal position (+0.27 mm), and the arterial dilatation for an increase in flow (0.98 ± 0.08 and 1.68 ± 0.06 mm mL^?1 min^?1 × 1000, respectively) was larger (P < 0.01) than occurred while supine (0.41 ± 0.05 mm mL^?1 min^?1 × 1000). Nitroglycerine‐mediated vasodilatation at 60° HUT was similar to that in the supine position. Conclusion: The orthostatic stimulus is associated with an increase of the flow‐mediated brachial artery vasodilatation, which is proportional to the degree of displacement. The mechanism of this effect does not consist of changes in nitric oxide sensitivity.     

Effect of beta blockade with and without sympathomimetic activity (ISA) on sympathovagal balance and baroreflex sensitivity.

Beta blockers increase heart rate variability (HRV) and improve survival in coronary artery disease (CAD). The benefit of beta blockers with intrinsic sympathomimetic activity (ISA) in CAD still remains a matter of debate, and their effect on HRV has not yet been investigated. Therefore, we measured HRV, systolic blood pressure variability (BPV) and baroreflex sensitivity (BRS) under propranolol (PROP, without ISA, 160 mg q.d.), pindolol (PIN, with potent ISA, 15 mg q.d.) and placebo (PLA, q.d.) in 30 healthy subjects, aged 21-39 years, during controlled frequency breathing (0.30 Hz) in supine and tilt positions. PROP increased HRV in the high-frequency (0.15-0.40 Hz) band (PROP 7.4 +/- 1.0; PLA 6.9 +/- 1.4; PIN 6.8 +/- 1.0 ln MI2; P = 0.003), decreased BPV in the low-frequency band (at 0.1 Hz, Mayer waves) (PROP 0.6 +/- 0.7; PLA 1.3 +/- 1.1; PIN 1.2 +/- 1.2 ln mmHg2; P = 0.001) and enhanced BRS (PROP 14.6 +/- 9.5; PLA 8.0 +/- 6.8; PIN 8.7 +/- 6.8 ms mmHg-1; P = 0.001) in the supine position. After passive tilt, PROP decreased HRV in the low-frequency band (PROP 6.1 +/- 0.9; PLA 6.5 +/- 1.1; PIN 6.9 +/- 0.7 ln MI2; P < 0.001) and decreased Mayer waves (PROP 1.8 +/- 0.8; PLA 2.4 +/- 1.0; PIN 2.7 +/- 0.8 ln mm Hg2; P < 0.001). PIN increased the low-frequency HRV response, which is induced by passive tilt (PIN + 0.9 +/- 1.0; PLA + 0.3 +/- 1.3, PROP + 0.3 +/- 1.0 ln MI2; P = 0.026). Our results prove that beta-adrenergic blockade with potent ISA does not increase HRV, has no beneficial effect on autonomic balance and even exaggerates sympathetic responses to passive tilt.     

Effect of hydration on some orthostatic and haematological responses to head-up tilt

Summary Experiments were undertaken to determine the effects of hydration status on a) orthostatic responses, and on b), relative changes in intravascular volume and protein content, during 70 head-up tilt (HUT). Six men underwent 45 min of HUT, preceded by 45 min supine, first dehydrated, and again 105 min later after rehydration with water. Heart rate was consistently lower following rehydration (p<0.01), while supine diastolic pressure was higher (p<0.02). Systolic pressure fell during dehydrated HUT (p<0.01), but not during rehydrated HUT. Postural haemoconcentration, which was reduced after rehydration (p<0.001), was accompanied by a decrease in intravascular albumin content (p<0.05). Two subjects experienced severe presyncopal symptoms during dehydrated HUT, but not during rehydrated HUT. Thus, it appears that rehydration after fluid restriction improves orthostatic tolerance. Furthermore, extravascular hydration status may be more important than intravascular hydration status in determining orthostatic tolerance.     

Relationship among nausea,anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea

This study evaluated the relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea. We enrolled 48 patients (36 females) aged 15 ± 2 years. Patients completed the Nausea Profile, State-Trait Anxiety Inventory for Children and underwent 70° head upright tilt testing (HUT) to assess for orthostatic intolerance (OI) and measure heart rate variability (HRV). We found nausea to be significantly associated with trait anxiety, including total nausea score (r = 0.71, p < 0.01) and 3 subscales: somatic (r = 0.64, p < 0.01), gastrointestinal (r = 0.48, p = 0.01), and emotional (r = 0.74, p < 0.01). Nausea was positively associated with state anxiety, total nausea (r = 0.55, p < 0.01), somatic (r = 0.48, p < .01), gastrointestinal (r = .30, p < .05), and emotional (r = .64, p < .01) subscales. Within 10 min of HUT, 27 patients tested normal and 21 demonstrated OI. After 45 min of HUT, only 13 patients (27 %) remained normal. Nausea reported on the Nausea Profile before HUT was associated with OI measured at 10 min of tilt (nausea total r = 0.35, p < 0.05; nausea emotional subscale r = 0.40, p < 0.01) and lower HRV at 10 min of HUT (F = 6.39, p = 0.01). We conclude that nausea is associated with both anxiety symptoms and OI. The finding of decreased HRV suggests an underlying problem in autonomic nervous system function in children and adolescents with chronic unexplained nausea.     

Human cardiovascular reactions to simulated hypovolaemia,modified by the opiate antagonist naloxone

Summary Six healthy males were exposed to 20 mm Hg lower body negative pressure (LBNP) for 8 min followed by 40 mm Hg LBNP for 8 min. Naloxone (0.1 mg·kg^–1) was injected intravenously during a 1 h resting period after which the LBNP protocol was repeated. Systolic, mean, and diastolic arterial blood pressures (SAP, MAP, DAP), and central venous pressure (CVP) were obtained using indwelling catheters. Cardiac output (CO), forearm blood flow (FBF), heart rate (HR), left ventricular ejection time (LVET), and electromechanical systole (EMS) were measured non-invasively. Pulse pressure (PP), stroke volume (SV), total peripheral resistance (TPR), forearm vascular resistance (FVR), systolic ejection rate (SER), pre-ejection period (PEP), PEP/LVET and indices for the systolic time intervals (LVETI, EMSI, PEPI) were calculated. During the second LBNP exposure, only two parameters differed from the pre-injection values: DAP at LBNP=40 mm Hg increased from 60.0±4.8 mm Hg to 64.8±4.1mm Hg (N=4, p<0.02) and LVETI at LBNP=20 mm Hg increased from 384.4±5.2 ms to 396.8±6.2 ms (N=6, p<0.02). In connection with the injection, SAP increased from 128.5±4.2 mm Hg to 134.3±5.4 mm Hg (N=6, p<0.025), PP from 56.5+-2.8 mm Hg to 62.7±3.5 mm Hg (N=6, p<0.01), HR from 54.0±3.1min^–1 to 59.2±4.1 min^–1 (N=6, p<0.01), and LVETI from 407.0±5.6 ms to 413.1±6.0 ms (N=6, p<0.02). This study suggests that endorphins do not have a significant action on the cardiovascular system in the compensated stage of hypovolaemic shock in humans. We found, however, weak evidence that naloxone increases SAP, HR, and LVETI during rest.     

Modulation of plasma adrenomedullin by epinephrine infusion during head up tilt

We investigated whether head up tilt (HUT) with and without simultaneous epinephrine infusion modulate plasma adrenomedullin. We studied eight healthy male volunteers, using two 5 min 70° HUT trials: control (saline infusion) and intervention (epinephrine infusion, titrated to a dose which increased supine systolic pressure by 20% above resting values). Protocols were randomized and separated by 2 weeks. Cardiac function and systolic time intervals, recorded using a phonocardiograph microphone, included left ventricular ejection time (LVET), pre-ejection period (PEP), PEP/LVET and electromechanical systole (QS2). Compared to saline infusion, epinephrine increased supine adrenomedullin (3.2 ± 0.8 pmol/l, i.e., mean ± SEM, respectively), heart rate (HR) (+11.3 ± 2.6 bpm), systolic pressure (+18.4 ± 2.6 mmHg) but decreased supine LVET, LVET corrected for HR (LVETi) and QS2-time (all p = 0.004). Despite similar HUT induced thoracic fluid shifts, reflected by similar thoracic impedance changes, HUT-induced adrenomedullin increases were minimal in epinephrine-supplemented men in comparison to controls (+8% vs. 42%). During HUT, epinephrine infusion decreased only the LVET (p = 0.039). Our findings confirm that short-term HUT increases plasma adrenomedullin. They further suggest that with increased supine epinephrine levels (epinephrine infusion clamping systolic arterial pressure at 120% control level), supine cardiac performance rises to a level similar to that during HUT, while adrenomedullin is still elevated with HUT. This might be in accordance with a ‘dampening’ role of adrenomedullin during catecholaminergic cardiovascular stimulation. As epinephrine is used as a drug to treat cardiac arrest and ventricular arrhythmias, our results may have important clinical/emergency resuscitation applications.     

The behaviour of the flow-mediated brachial artery vasodilatation during orthostatic stress in normal man

AIMS: Flow-mediated brachial artery vasodilatation is an index of endothelial function. Published literature describes only supine data and no study has been performed during vertical displacement. This subject deserves investigation for two main reasons: humans spend the larger part of their life in the upright position; this position has significant effects on neural vascular regulation. METHODS: In 21 healthy men (25 +/- 2 years) the flow-dependent brachial artery vasodilating response to distal circulatory arrest was assessed by Doppler ultrasound imaging, while supine and during 20 degrees and 60 degrees head-up tilting (HUT). In 11 of these subjects the vasodilating response to nitroglycerine was also explored. RESULTS: Absolute and percentage increments in brachial calibre during hyperaemia after deflation of the occluding cuff became increasingly greater at 20 degrees (+0.44 mm) and 60 degrees (+0.92 mm) HUT (P < 0.01), compared with the horizontal position (+0.27 mm), and the arterial dilatation for an increase in flow (0.98 +/- 0.08 and 1.68 +/- 0.06 mm mL(-1) min(-1) x 1000, respectively) was larger (P < 0.01) than occurred while supine (0.41 +/- 0.05 mm mL(-1) min(-1) x 1000). Nitroglycerine-mediated vasodilatation at 60 degrees HUT was similar to that in the supine position. CONCLUSION: The orthostatic stimulus is associated with an increase of the flow-mediated brachial artery vasodilatation, which is proportional to the degree of displacement. The mechanism of this effect does not consist of changes in nitric oxide sensitivity.     

Beat-to-beat noninvasive stroke volume from arterial pressure and Doppler ultrasound

The proper understanding of the cardiovascular mechanisms involved in complaints of short-lasting dizziness and the evaluation of unexplained recurrent syncope requires continuous monitoring of cardiac stroke volume (SV) in addition to blood pressure and heart rate. The primary aim of the present study was to evaluate a pulse wave analysis method that calculates beat-to-beat flow from non-invasive arterial pressure by simulating a non-linear, time-varying model of human aortic input impedance (Modelflow; MF), by comparing MF stroke volume (SV_MF) to Doppler ultrasound (US) flow velocity SV (SV_US). A second purpose was to compare the two methods under two different conditions: the supine and head-up tilt (30°) position. SV_US and SV_MF with non-invasive arterial pressure (Finapres) as input to the aortic model were measured beat-to-beat during spontaneous supine breathing and in the passive 30° head-up tilt (HUT30) position in six normotensive healthy humans [three females, mean age 24 (21–26) years]. There were variations in supine SV track between the two methods with zero difference and a SD of the beat-to-beat difference (MF–US) of 4.2%. HUT30 induced a systematic difference of 10.5% and an increase in SD to 6.9%, which was reproducible. Beat-to-beat changes in SV in the supine resting condition were equally well assessed by both methods. Systematic differences appear during HUT30 and show opposite signs. The difference between the two methods upon a change in body position may be attributed to limitations in each method.     

Impaired brachial artery endothelial flow-mediated dilation and orthostatic stress in hemodialysis patients

PURPOSE: Chronic kidney disease (CKD) is associated with an impaired endothelial function, which may contribute to cardiovascular events. Whether impairment in endothelial function is involved in the circulatory response to orthostatic stress is unknown. We assessed endothelial function via brachial artery flow-mediated dilation (BAFMD), an index of endothelial-dependent vasodilation. METHODS: We measured changes in brachial artery diameter (BAD) and blood flow by Doppler ultrasound in 35 CKD patients on hemodialysis, 37 young healthy controls (HC) and 50 non-uremic matched controls (MC), in the supine position and after 60 degrees head-up tilting (HUT). Results: In the supine position, endothelial flow-mediated BAD was significantly increased in HC (p<0.001) and MC (p<0.01) while no significant changes were detected in CKD. Mean percent blood flow changes were HC+323.5%, MC+195.1% and CKD+158.8% (HC vs. CKD p<0.001; HC vs. MC p<0.001; MC vs. CKD p=0.04). Similarly, during HUT mean BAD and blood flow increases were significantly impaired in CKD patients. CONCLUSION: In CKD patients, an impaired response in the physiologic vascular reactivity, suggesting endothelial dysfunction, was found in the supine position and after orthostasis by BAFMD. Our results are in favor of a possible adjunctive role of uremia in the abnormal brachial artery response.     

Systolic stretching of the ascending aorta

IntroductionLongitudinal stretching of the aorta due to systolic heart motion contributes to the stress in the wall of the ascending aorta. The objective of this study was to assess longitudinal systolic stretching of the aorta and its correlation with the diameters of the ascending aorta and the aortic root.Material and methodsAortographies of 122 patients were analyzed. The longitudinal systolic stretching of the aorta caused by the contraction of the heart during systole and the maximum dimensions of the aortic root and ascending aorta were measured in all patients.ResultsThe maximum dimension of the aortic root was on average 34.9 ±4.5 mm and the mean diameter of the ascending aorta was 33.9 ±5.4 mm. The systolic aortic stretching negatively correlated with age (r = –0.49, p < 0.001) and the diameter of the tubular ascending aorta (r = –0.44, p < 0.001). There was no significant correlation between the stretching and the dimension of the aortic root (r = –0.11, p = 0.239). There was a statistically significant (p < 0.001) difference in the longitudinal aortic stretching values between patients with a normal aortic valve (10.6 ±3.1 mm) and an aortic valve pathology (8.0 ±3.2 mm in all patients with an aortic valve pathology; 7.5 ±4.3 mm in isolated aortic stenosis, 8.5 ±2.9 mm in the case of isolated insufficiency, 8.2 ±2.8 mm for valves that were both stenotic and insufficient).ConclusionsSystolic aortic stretching negatively correlates with the diameter of the tubular ascending aorta and the age of the patients, and does not correlate with the diameter of the aortic root. It is lower in patients with an aortic valve pathology.     

Evaluation of the Surgical Margin Threshold for Avoiding Recurrence after Partial Nephrectomy in Patients with Renal Cell Carcinoma

PurposeAn adequate minimal surgical margin for partial nephrectomy (PN) has not yet been conclusively established. Therefore, we aimed to compare PN recurrence rates according to surgical margin status and to establish an adequate minimal surgical margin.Materials and MethodsWe retrospectively studied patients with clinically localized renal cell carcinoma who underwent PN between 2005 and 2014. Surgical margin width (SMW) was assessed for all surgical tissues and divided into three groups: SMW <1 mm, SMW ≥1 mm, and positive surgical margin (PSM). The data were analyzed using the Kaplan-Meier method with log-rank tests and multivariate Cox regression models.ResultsOf 748 patients (median age, 55 years; interquartile range, 46–64 years; 220 female), 704 (94.2%) and 44 (5.8%) patients had negative and PSMs, respectively. Recurrence-free survival was significantly lower in patients with PSMs (p<0.001) and was not significantly different between SMW ≥1 mm and <1 mm groups (p=0.604). PSM was a significant predictor of recurrence (hazard ratio: 8.03, 95% confidence interval: 2.74–23.56, p<0.001), in contrast to SMW <1 mm (p=0.680).ConclusionA PSM after PN significantly increases the risk of recurrence. We discovered that even a submillimeter safety surgical margin may be enough to prevent recurrence. To maximize normal renal parenchyma preservation and to avoid cancer recurrence in renal parenchymal tumor patients, PN may be a safe treatment, except for those with a PSM in the final pathology.     

Comparison of sublingual isosorbide dinitrate and Valsalva maneuver for detection of obstruction in hypertrophic cardiomyopathy

Introduction

A left ventricular outflow tract (LVOT) obstruction assessment with a provoking test should be a routine part of the evaluation of patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to compare the utility of the Valsalva maneuver (VM) and sublingual spray application of isosorbide dinitrate (ISDN) for detection of an obstruction.

Material and methods

We prospectively evaluated 81 consecutive HCM patients without severe rest LVOT obstruction (defined as peak rest pressure gradient (PG) ≥ 50 mm Hg). We measured PG at rest, during the VM, after sublingual ISDN spray, and during the VM after ISDN. An obstruction was defined as a PG ≥ 30 mm Hg.

Results

An obstruction was present in 15 patients (19%) at rest (median and interquartile range of PG 16 (7–26) mm Hg), in 38 patients (47%) during the VM (PG 28 (12–49) mm Hg), in 50 (62%) patients after ISDN (PG 50 (12–79) mm Hg), and in 55 patients (68%) during the VM after ISDN (PG 59 (20–87) mm Hg). The difference in occurrence of obstruction among different provoking tests was statistically significant for all comparisons (p < 0.001, except for the comparison of the ISDN test with the VM during ISDN, p = 0.025).

Conclusions

The ISDN test and the VM are useful screening methods for the detection of an HCM obstruction. Although ISDN appears to be more precise than the VM, the best option is a combination of both methods, which maximizes inducement of LVOT obstruction in patients with HCM.     

Hepatic Venous Pressure Gradient Predicts Long-Term Mortality in Patients with Decompensated Cirrhosis

Purpose

The present study aimed to investigate the role of hepatic venous pressure gradient (HVPG) for prediction of long-term mortality in patients with decompensated cirrhosis.

Materials and Methods

Clinical data from 97 non-critically-ill cirrhotic patients with HVPG measurements were retrospectively and consecutively collected between 2009 and 2012. Patients were classified according to clinical stages and presence of ascites. The prognostic accuracy of HVPG for death, survival curves, and hazard ratios were analyzed.

Results

During a median follow-up of 24 (interquartile range, 13-36) months, 22 patients (22.7%) died. The area under the receiver operating characteristics curves of HVPG for predicting 1-year, 2-year, and overall mortality were 0.801, 0.737, and 0.687, respectively (all p<0.01). The best cut-off value of HVPG for predicting long-term overall mortality in all patients was 17 mm Hg. The mortality rates at 1 and 2 years were 8.9% and 19.2%, respectively: 1.9% and 11.9% with HVPG ≤17 mm Hg and 16.2% and 29.4% with HVPG >17 mm Hg, respectively (p=0.015). In the ascites group, the mortality rates at 1 and 2 years were 3.9% and 17.6% with HVPG ≤17 mm Hg and 17.5% and 35.2% with HVPG >17 mm Hg, respectively (p=0.044). Regarding the risk factors for mortality, both HVPG and model for end-stage liver disease were positively related with long-term mortality in all patients. Particularly, for the patients with ascites, both prothrombin time and HVPG were independent risk factors for predicting poor outcomes.

Conclusion

HVPG is useful for predicting the long-term mortality in patients with decompensated cirrhosis, especially in the presence of ascites.     

Bone Response to High-Intensity Interval Training versus Moderate-Intensity Continuous Training in Adolescents with Obesity

IntroductionSince adolescents with obesity are prone to bone fragility during weight loss, the aim was to compare the impact of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on bone density, geometry, and strength.MethodsSixty-one adolescents were randomly assigned to 2 cycling trainings (HIIT and MICT) and a control (CTR, without training) group. Anthropometry, dual-energy X-ray absorptiometry with hip structural analysis and the trabecular bone score (TBS) were assessed before and after the 16-week intervention.ResultsBody mass index (BMI) and fat mass (FM) percentage decreased at T1 versus T0 in both training groups (p < 0.001 for HIIT, p = 0.01 for MICT), though to a larger extent in HIIT (p < 0.05). Total body bone mineral density (BMD) and bone mineral content (BMC) increased in both training groups (p < 0.001), but to a greater extent in HIIT for BMC (p < 0.05). Lumbar spine BMD and BMC increased in both training groups (p < 0.001 for HIIT, p < 0.01 for MICT), with a time × group interaction between HIIT and CTR (p < 0.05) only. TBS increased in both training groups (p < 0.01 for HIIT, p < 0.05 for MICT). Hip BMD and BMC increased in both HIIT (p < 0.001 and p < 0.01) and MICT (p < 0.01 and p < 0.05). At the narrow neck (NN), endocortical diameter, width (p < 0.01), cross-sectional moment of inertia, and section modulus (Z) (p < 0.05) increased only in the HIIT group, such as BMD and Z (p < 0.05) at the intertrochanteric region (IT) and average cortical thickness (p < 0.001) and width (p < 0.05) at the femoral shaft. At the NN and IT, the buckling ratio decreased only in the HIIT group (p < 0.05), predicting higher resistance to fracture.ConclusionsIn addition to inducing greater BMI and FM percentage decreases in comparison to MICT, HIIT improves multisite bone density, geometry, and strength, which heighten the justification for HIIT as part of weight loss interventions in adolescents with obesity.     

Prognostic value of low-dose dobutamine stress echocardiography in patients with aortic stenosis and impaired left ventricular function

Introduction

The aim of this multicenter, prospective study was to evaluate the long-term prognostic value of low-dose dobutamine stress echocardiography (LDDSE) in patients with aortic stenosis (AS) and depressed left ventricular (LV) function.

Material and methods

The study group comprised 39 patients (34 male, mean age 59 ±13 years) with AS (peak gradient > 25 mm Hg), LV ejection fraction (LVEF) ≤ 45% and low transaortic gradient (peak gradient ≤ 45 mm Hg, mean gradient ≤ 35 mm Hg). The qualification for subsequent therapeutic procedures was based on generally accepted indications. All patients underwent LDDSE and coronary angiography. Twelve months after LDDSE patients underwent control resting echocardiography and clinical evaluation.

Results

Twenty-seven (69.2%) patients had preserved contractile reserve. In this subgroup, true-severe AS was diagnosed in 12 patients, whereas pseudo-severe AS was found in 15 patients. Nine patients with true-severe AS, 2 patients with pseudo-severe AS and 7 patients without contractile reserve were referred for surgical treatment. The independent risk factors of death during follow-up were: aortic valve area (AVA) at peak stress < 0.8 cm² (OR 1.4; p = 0.003) and LVEF at rest < 35% (OR 6.8; p = 0.05). The independent risk factors of composite end-point (death or myocardial infarctions or pulmonary edema) were: AVA at stress < 0.8 cm² (OR 4.0; p = 0.03), absence of AVA increase during LDDSE (OR 5.7; p = 0.005), absence of contractile reserve (OR 4.5; p = 0.01) and presence of significant CAD (OR 6.9; p = 0.02).

Conclusions

In patients with AS and depressed LVEF, LDDSE is a useful tool for long-term risk stratification.     

Use of Liraglutide 3.0 mg for Weight Management in a Real-World Setting in Switzerland

IntroductionData from randomized controlled trials show that liraglutide 3.0 mg, in combination with diet and exercise, is associated with greater weight loss than diet and exercise alone in patients with obesity. In practice, the utilization of weight loss drugs is influenced by various factors, including the cost of treatment. We conducted a retrospective, observational study to assess the effectiveness of liraglutide 3.0 mg and patients'' persistence on treatment, in a real-world setting.MethodsData were extracted from de-identified electronic medical records from an obesity management clinic in Switzerland. Changes in body weight and blood pressure were evaluated in the full cohort (N = 277, 19% of whom had undergone bariatric surgery) and subgroups who were persistent on liraglutide 3.0 mg for at least 4 months (n = 236), 7 months (n = 159), or 12 months (n = 71).ResultsMedian persistence on liraglutide was 6.8 months. Median maximum dose received was 1.5 mg, and 13.7% of patients reached the maintenance dose of 3.0 mg. Mean 7-month weight change from baseline in the full cohort was −4.1 kg (95% confidence interval: −5.0, −3.2; p < 0.001; −4.2%). Weight change was −4.4 kg (−4.7%) in the ≥4-month persistence subgroup at 4 months, −5.1 kg (−5.3%) in the ≥7-month persistence subgroup at 7 months, and −7.5 kg (−7.1%) in the ≥12-month persistence subgroup at 12 months (all p < 0.001). In the full cohort, 40% and 14% of patients lost ≥5% and >10% of body weight at 7 months, respectively. Weight loss did not differ significantly according to history of bariatric surgery (p = 0.94). Diastolic blood pressure decreased (from 87.0 to 83.9 mm Hg at 7 months; p = 0.018), with no significant changes in systolic blood pressure. Approximately two-thirds of patients did not have health insurance that could cover the cost of liraglutide.ConclusionIn a real-world setting with low insurance coverage and with most patients not reaching the recommended maintenance dose of 3.0 mg, the use of liraglutide, in combination with diet and exercise, was associated with clinically meaningful weight loss.