Thirty-Nine Percent of Patients with a Ruptured Abdominal Aortic Aneurysm (AAA) Have an Incidentally Detected AAA Prior to Rupture.

BACKGROUND: Abdominal aortic aneurysm (AAA) screening has been offered to 65-year-old men living in Oslo, Norway, since May 2011. A significant number of AAA-related deaths occurred in individuals who are not eligible for screening. The primary aim of this study was to describe the group of patients admitted to Oslo University Hospital with a ruptured AAA after the implementation of the local AAA screening project. The following parameters were investigated: AAA detection before rupture, surveillance status, eligibility for screening, and comorbidities. We also sought to compare outcomes (repair rates and 30-day mortality) between patients with and without an incidentally detected AAA prior to rupture. METHODS: This cohort study included patients admitted acutely to Oslo University Hospital due to a symptomatic or ruptured AAA in the period January 2011 to December 2022. Data on demographics, prior AAA detection, surveillance status, treatment, and mortality were collected retrospectively through electronic medical records. RESULTS: We identified 200 patients with a symptomatic or ruptured AAA, among which 79 (40%) had an AAA detected before rupture-one (1%) through screening and 78 (39%) incidentally. Up to 30% of the incidentally detected AAAs were not under any surveillance. Six patients were found eligible for screening: one had attended, three were non-attenders, and two had not been invited. Patients with an incidentally detected AAA before rupture had a more advanced age and a significantly higher degree of comorbidities than patients without a previously detected AAA, and the repair rates in these groups were 56% and 84%, respectively (P < 0.001). Adjusted for comorbidities and risk factors, the odds ratio for repair among patients with incidentally detected AAA was 0.56 (P = 0.292). The 30-day mortality was not significantly different between the two groups (P = 0.097). CONCLUSIONS: Most patients with a ruptured AAA were not eligible for screening, but 39% of the patients had an incidentally detected AAA prior to rupture. Standardized reporting and follow-up of incidentally detected AAAs is thus identified as an additional measure to organized screening in the effort to reduce AAA-related mortality.

Three-dimensional ultrasound volume and conventional ultrasound diameter changes are equally good markers of endoleak in follow-up after endovascular aneurysm repair.

INTRODUCTION: The main disadvantages of computed tomography angiography (CTA) in follow-up after endovascular aneurysm repair are the risks of contrast-induced renal impairment and radiation-induced cancer. Three-dimensional ultrasound is a new technique for volume estimation of the aneurysm sac. Some studies have reported promising results. The aim of this study was to evaluate the accuracy and precision of three-dimensional ultrasound aneurysm sac-volume estimates, and to explore whether volume and/or diameter changes on ultrasound can be used as markers of endoleak. METHODS: A single-center diagnostic accuracy study was performed. A total of 92 patients planned for endovascular aneurysm repair were prospectively and consecutively enrolled (2013-2016). Aneurysm sac diameter and volume were measured using CTA, conventional ultrasound, and three-dimensional ultrasound preoperatively and 1, 6, 12, and 24 months postoperatively. Three-dimensional ultrasound was performed with a commercially available electromechanical transducer. Patients with endoleak were observed 5 years after endovascular aneurysm repair. RESULTS: A total of 79 men and 13 women were included. Mean age was 74 years (57-92 years). Median follow-up was 24 months. Endoleak cases were observed for up to 55 months. Diameter measurements on conventional ultrasound correlated well with CT diameters (r = 0.9, P < .05, n = 347), and Bland-Altman analyses showed an upper limit of agreement of +0.5 cm and a lower limit of agreement of -0.8 cm. The mean difference was -0.13 cm ± 0.36 cm. Three-dimensional ultrasound volumes had a correlation with CTA diameters of r = 0.8 (P < .05, n = 347) and with three-dimensional CT volumes of r = 0.8 (P < .05, n = 155). Receiver operating characteristic analyses showed that the diameter and volume changes that led to reintervention were most accurate at 24-month follow-up, with area-under-the-curve percentage changes of 0.98 (two-dimensional ultrasound), 0.97 (three-dimensional ultrasound), and 0.97 (two-dimensional CT). DISCUSSION: Both diameter and volume changes can be used as markers for endoleak with excellent areas under the curve on receiver operating characteristic analyses. However, three-dimensional ultrasound volumes did not add any further diagnostic information. Conventional 2D diameter measurements were as accurate as volume changes as markers of endoleak. CONCLUSIONS: Type II endoleaks can safely be followed up using a simple diameter measurement on conventional ultrasound.

The Effect of 12-Week Treatment with Intermittent Negative Pressure on Blood Flow Velocity and Flowmotion, Measured with a Novel Doppler Device (Earlybird). Secondary Outcomes from a Randomized Sham-Controlled Trial in Patients with Peripheral Arterial Disease.

BACKGROUND: Treatment with intermittent negative pressure (INP) is proposed as an adjunct to standard care in patients with peripheral arterial disease (PAD). The aims of this study were to evaluate the applicability of a novel ultrasound Dopplerdevice (earlybird) to assess blood flow characteristics in patients with PAD during a treatment session with INP, and whether certain flowproperties could determine who could benefit from INP treatment. METHODS: Secondary outcomes of data from a randomized sham-controlled trial were explored. Patients were randomized to 12 weeks of treatment with 40 mm Hg or 10 mm Hg INP, for one hour twice daily. Earlybird blood flow velocity recordings were made before and after the 12-week treatmentperiod and consists of a 5-min recording in rest, 3-min during INP treatment and 5-min recording after ended INP test-treatment. Mean blood flow velocity (vmean), relative changes in flow and frequency spectrum by Fourier-transform of the respective bandwidths of endothelial, sympathetic, and myogenic functions, were analyzed for the different series of blood flow measurements. RESULTS: In total, 62 patients were eligible for analysis, where 32 patients were treated with 40 mm Hg INP. The acquired recordings were of good quality and were used for descriptive analyses of flow characteristics. An immediate increase in vmean during the negative pressure periods of the INP test-treatment was observed in the 40 mm Hg INP treatment group at both pre- and post-test. There was a significant difference between the treatment groups, with a difference between the medians of 13.7 (P < 0.001) at pre-test and 10.7 (P < 0.001) at posttest. This finding was confirmed with spectrum analysis by Fourier-transform of the bandwidth corresponding to INP treatment. The change in amplitude corresponding to myogenic function after 12-weeks of treatment, was significantly different in favor of the 40 mm Hg INP treatment group. We were not able to detect the specific flow characteristics indicating who would benefit INP-treatment. CONCLUSIONS: Earlybird is an applicable tool for assessing blood flow velocity in patients with PAD. Analysis of the flow velocity recordings shows that INP induces an immediate increase in blood flow velocities during INP. The positive effects of INP may be attributed to recruitment of arterioles, and thereby, increasing blood flow. In these analyses, no flow characteristics were determined which could predict who would benefit INP treatment.

A randomized controlled trial of treatment with intermittent negative pressure for intermittent claudication.

OBJECTIVE: We investigated the effects of lower extremity intermittent negative pressure (INP) treatment for 1 hour two times daily for 12 weeks on the walking distance of patients with intermittent claudication (IC). METHODS: Patients with IC were randomized to treatment with -40 mm Hg INP (treatment group) or -10 mm Hg INP (sham control group). Pain-free walking distance (PWD) and maximal walking distance (MWD) on a treadmill, resting and postexercise ankle-brachial index, resting and postischemic blood flow (plethysmography), and quality of life (EQ-5D-5L and Vascuqol-6) were measured at baseline and after 12 weeks of treatment. RESULTS: A total of 72 patients were randomized, and 63 had data available for the intention-to-treat analyses. The between-group comparisons showed a significant change in the PWD, favoring the treatment group over the sham control group (estimated treatment effect, 50 m; 95% confidence interval [CI], 11-89; P = .014). The PWD had increased by 68 m (P < .001) in the treatment group and 18 m (P = .064) in the sham control group. No significant difference was found in the change in the MWD between the two groups (estimated treatment effect, 42 m; 95% CI, -14 to 97; P = .139). The MWD had increased by 62 m (P = .006) in the treatment group and 20 m (P = .265) in the sham control group. For patients with a baseline PWD of <200 m (n = 56), significant changes had occurred in both PWD and MWD between the two groups, favoring the treatment group (estimated treatment effect, 42 m; 95% CI, 2-83; P = .042; and estimated treatment effect, 62 m; 95% CI, 5-118; P = .032; respectively). Both overall and for the group of patients with a PWD <200 m, no significant differences were found in the changes in the resting and postexercise ankle-brachial index, resting and postischemic blood flow, or quality of life parameters between the two groups. CONCLUSIONS: Treatment with -40 mm Hg INP increased the PWD compared with sham treatment in patients with IC. For the patients with a baseline PWD of <200 m, an increase was found in both PWD and MWD compared with sham treatment.

Effects of intermittent negative pressure treatment on circulating vascular biomarkers in patients with intermittent claudication.

The aim of this study was to investigate the effects of lower extremity intermittent negative pressure (INP) treatment for 1 hour twice daily for 12 weeks, on circulating vascular biomarkers in patients with intermittent claudication. Patients were randomized to treatment with -40 mmHg INP (treatment group), or -10 mmHg INP (sham control group). Venous blood samples were collected at baseline and after 12 weeks, and concentrations of vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin, von Willebrand factor (vWF), l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were analyzed. A larger proportion of the patients in the treatment group (25/31) had a reduction in vWF levels after 12 weeks, compared to the sham control group (17/30) (p = 0.043). Within the treatment group there was a significant mean (SEM) reduction in the concentration of vWF of -11% (4) (p = 0.019), whereas there was no significant change in the levels of vWF in the sham control group (1% (6); p = 0.85). There were no significant differences in the change of any of the biomarker levels between the groups after 12 weeks of treatment. In conclusion, there were no differences in the change of the circulating levels of the measured biomarkers between the treatment group and the sham control group after 12 weeks of INP treatment. However, the observed changes in vWF might indicate a beneficial effect of INP treatment on endothelial activation and endothelial injury. Clinicaltrials.gov Identifier: NCT03640676.

Lower Extremity Intermittent Negative Pressure for Intermittent Claudication. Follow-Up after 24 Weeks of Treatment.

BACKGROUND: Treatment with lower extremity intermittent negative pressure (INP) of -40 mm Hg for one hour twice daily for 12 weeks, increases walking capacity in patients with intermittent claudication (IC). However, the effects of INP treatment beyond 12 weeks have not been elucidated. The aim of the present study was to investigate the clinical effects of INP treatment after 24 weeks in patients with IC. METHODS: This was a follow-up study after a randomized sham-controlled trial, where patients randomized to the active treatment group were offered to continue treatment for 12 additional weeks (24 weeks in total). Treatment with -40 mm Hg INP was applied in a pressure chamber sealed around the lower leg, and the patients were instructed to treat themselves at home one hour in the morning and one hour in the evening. Pain free walking distance (PWD), maximal walking distance (MWD), resting ankle-brachial index (ABI) and post exercise ABI were measured at baseline, after 12 and 24 weeks. RESULTS: Ten out of 32 patients (31%) from the active treatment group in the initial trial were included in this follow-up study. At baseline, PWD was (mean ±SD) 151 ± 91 m and MWD was 362 ±159 m. There was a significant increase in both PWD and MWD after 24 weeks of treatment, compared to baseline (ANOVA; P= 0.006 and P= 0.012, respectively). Post hoc tests revealed that PWD increased significantly from baseline to 12 weeks (mean 81 m; 95% CI [6, 156]; P = 0.032), and that MWD increased significantly from 12 to 24 weeks (mean 145 m; 95% CI [22, 268]; P = 0.018). There were no significant changes in resting ABI or post exercise ABI during the 24-week treatment period (ANOVA; P= 0.157 and P= 0.450, respectively). CONCLUSION: Both PWD and MWD improved after treatment with - 40 mm Hg INP for one hour twice daily for 24 weeks, compared to baseline. The main improvement in PWD occurred during the first 12 weeks of treatment, whereas the main improvement in MWD occurred between 12 and 24 weeks of treatment.

Cerebral blood flow velocity during simultaneous changes in mean arterial pressure and cardiac output in healthy volunteers.

PURPOSE: Cerebral blood flow (CBF) needs to be precisely controlled to maintain brain functions. While previously believed to be autoregulated and near constant over a wide blood pressure range, CBF is now understood as more pressure passive. However, there are still questions regarding the integrated nature of CBF regulation and more specifically the role of cardiac output. Our aim was, therefore, to explore the effects of MAP and cardiac output on CBF in a combined model of reduced preload and increased afterload. METHOD: 16 healthy volunteers were exposed to combinations of different levels of simultaneous lower body negative pressure and isometric hand grip. We measured blood velocity in the middle cerebral artery (MCAV) and internal carotid artery (ICAV) by Doppler ultrasound, and cerebral oxygen saturation (ScO2) by near-infrared spectroscopy, as surrogates for CBF. The effect of changes in MAP and cardiac output on CBF was estimated with mixed multiple regression. RESULT: Both MAP and cardiac output had independent effects on MCAV, ICAV and ScO2. For ICAV and ScO2 there was also a statistically significant interaction effect between MAP and cardiac output. The estimated effect of a change of 10 mmHg in MAP on MCAV was 3.11 cm/s (95% CI 2.51-3.71, P < 0.001), and the effect of a change of 1 L/min in cardiac output was 3.41 cm/s (95% CI 2.82-4.00, P < 0.001). CONCLUSION: The present study indicates that during reductions in cardiac output, both MAP and cardiac output have independent effects on CBF.

Contrast-enhanced ultrasound detects type II endoleaks during follow-up for endovascular aneurysm repair.

OBJECTIVE: Repeated computed tomography angiography (CTA) can be used during follow-up visits for endovascular aneurysm repair (EVAR) but leads to accumulated radiation exposure and may cause renal impairment. Therefore, the use of contrast-enhanced ultrasound (CEUS) has increased, and its ability to detect endoleaks has been promising. The aim of this study was to investigate the diagnostic accuracy of CEUS vs CTA for endoleak detection during EVAR follow-up. METHODS: Ninety-two patients with planned EVAR for abdominal aortic aneurysm were prospectively, consecutively enrolled. In total, 233 paired CTA and CEUS procedures were performed within the same day. Follow-up visits occurred 1 month, 6 months, 12 months, and 24 months postoperatively. RESULTS: Of 48 endoleaks discovered by CTA, 39 were also detected on CEUS, giving an overall sensitivity of 81.3% and specificity of 98.9%. All undetected endoleaks were minor, without clinical importance, and occurred in patients with high body mass index. CONCLUSIONS: In this study, CEUS was accurate for detecting type II endoleaks during follow-up visits for EVAR. Sensitivity was lower in obese patients. Doppler ultrasound has low sensitivity and seems to be unsuitable for the detection of endoleaks.

Lung function and oxygen saturation after participation in Norseman Xtreme Triathlon.

OBJECTIVES: To examine evidence of exercise-induced bronchoconstriction (EIB) defined as ≥10% reduction in forced expiratory volume in one second (FEV1 ) and exercise-induced arterial hypoxemia (EIAH) defined as ≥4% reduction in oxygen saturation (SpO2 ) from before to after participation in the Norseman Xtreme Triathlon. Secondarily, to assess whether changes in FEV1 and SpO2 are related to respiratory symptoms, training volume, and race time. METHODS: In this quasi-experimental non-controlled study, we included 63 triathletes (50♂/13♀) aged 40.3 (±9.0) years (mean ± SD). Fifty-seven (46♂/11♀) measured lung function and 54 (44♂/10♀) measured SpO2 before the race, 8-10 minutes after the race (post-test 1) and the day after the race (post-test 2). Respiratory symptoms and training volume were recorded with modified AQUA questionnaire. ANOVA for repeated measures was used to detect differences in lung function and SpO2 . Statistical significance was accepted at 0.05 level. RESULTS: Twenty-six participants (46%) presented with EIB at post-test 1 and 16 (28%) at post-test 2. Lung function variables were significantly reduced from baseline to post-test 1 and 2. Thirty-five participants (65%) showed evidence of mild to moderate EIAH. No significant correlations were observed except a weak correlation between maximal reduction in FEV1 and respiratory symptoms (r = 0.35, P = .016). CONCLUSION: Our results demonstrated that 46% of the participants presented with EIB and 65% showed evidence of EIAH after the Norseman Xtreme Triathlon. Changes in FEV1 and SpO2 were not correlated to weekly training hours or race time. We observed a weak correlation between maximal reduction in FEV1 and respiratory symptoms.

Gastroscopy assisted laser Doppler flowmetry and visible light spectroscopy in patients with chronic mesenteric ischemia.

Mucosal pathology due to chronic mesenteric ischemia (CMI) is rarely seen during upper endoscopy. Combining Laser Doppler Flowmetry (LDF) and Visible Light Spectroscopy (VLS) may aid in detection of CMI at an early stage. We aimed to investigate the utility of LDF and VLS in detecting microcirculatory changes in patients with CMI during upper endoscopy. In a single center, prospective study, 104 patients were evaluated for mesenteric ischemia during a 24 months period. Patients with a consensus diagnosis of CMI (n = 40) were examined with LDF and VLS. Thirty-two were successfully treated and had a definitive diagnosis of CMI. Results were compared with controls (n = 38) with normal intestinal circulation evaluated with duplex ultrasonography (DUS). Treatment response was evaluated clinically and with DUS at 1 month and with VLS and LDF at 3 months. A significant reduction in mucosal capillary hemoglobin oxygen saturation (SO2) was found in CMI patients compared to controls before treatment: mean ± SD: 67 ± 9%, 81 ± 4%, respectively (p < .001). A significant reduction was also seen for the relative hemoglobin (rHb) amount, flow and velocity (p < .001). The sensitivity of SO2 measured by VLS for diagnosing CMI was 94% and the specificity 72% (cut-off 78%), calculated with ROC curve analysis. A combination of SO2 and rHb increased the test sensitivity and specificity to 97% and 79%, respectively. Conclusion: CMI patients have significantly reduced microcirculation in the stomach and duodenum compared to controls. The results suggest that VLS should be included when performing an upper endoscopy in patients with suspected CMI.

Intermittent mild negative pressure applied to the lower limb in patients with spinal cord injury and chronic lower limb ulcers: a crossover pilot study.

STUDY DESIGN: Randomized, assessor-blinded crossover pilot study. OBJECTIVES: To explore the use of an intermittent negative pressure (INP) device for home use in addition to standard wound care (SWC) for patients with spinal cord injury (SCI) and chronic leg and foot ulcers before conducting a superiority trial. SETTING: Patient homes and outpatient clinic. METHODS: A 16-week crossover trial on 9 SCI patients (median age: 57 years, interquartile range [IQR] 52-66), with leg ulcers for 52 of weeks (IQR: 12-82) duration. At baseline, patients were allocated to treatment with INP + SWC or SWC alone. After 8 weeks, the ulcers were evaluated. To assess protocol adherence, the patients were then crossed over to the other group and were evaluated again after another 8 weeks. Lower limb INP treatment consisted of an airtight pressure chamber connected to an INP generator (alternating 10 s -40mmHg/7 s atmospheric pressure) used 2 h/day at home. Ulcer healing was assessed using a photographic wound assessment tool (PWAT) and by measuring changes in wound surface area (WSA). RESULTS: Seven of nine recruited patients adhered to a median of 90% (IQR: 80-96) of the prescribed 8-week INP-protocol, and completed the study without side effects. PWAT improvement was observed in 4/4 patients for INP + SWC vs. 2/5 patients for SWC alone (P = 0.13). WSA improved in 3/4 patients allocated to INP + SWC vs. 3/5 patients in SWC alone (P = 0.72). CONCLUSIONS: INP can be used as a home-based treatment for patients with SCI, and its efficacy should be tested in an adequately sized, preferably multicenter randomized trial.

Intermittent negative pressure applied to the lower limb increases foot macrocirculatory and microcirculatory blood flow pulsatility in people with spinal cord injury.

STUDY DESIGN: Experimental prestudy and poststudy. OBJECTIVES: Examine the acute effects of intermittent negative pressure (INP) applied to the lower limb on foot circulation in people with spinal cord injuries (SCIs). SETTING: Vascular laboratory, Oslo University Hospital. METHODS: Twenty-four people with SCI (median age 59 years, range 29-74) were exposed to lower leg INP (-40 mm Hg) using an air-tight pressure chamber connected to an INP generator. The contralateral leg was placed outside the pressure chamber. We continuously measured arterial blood flow velocity (ultrasound Doppler), skin blood flow (laser Doppler), skin temperature of the dorsum of the foot, heart rate (ECG) and systemic blood pressure (Finometer) during 5-min baseline (atmospheric pressure), followed by 10-min INP (alternating 10 s -40 mm Hg and 7 s atmospheric pressure), and 5-min post-INP (atmospheric pressure). Skin blood flow was measured on the foot placed outside the pressure chamber. A mixed effects regression model was applied to estimate the effect of INP on blood flow. To quantify flow fluctuations, we calculated cumulative up-and-down changes in arterial blood flow velocity per minute. RESULTS: Flow fluctuations increased during INP compared to baseline [32.3 cm/s/min (95% CI 26.9 to 37.7) vs. 15.2 cm/s/min (95% CI 9.8 to 20.6), P < 0.001]. Peak blood flow velocity and skin blood flow was reached 2-3 s after the onset of negative pressure and increased 33% (95% CI 16 to 46, P < 0.001) and 11% (95% CI -4.1 to 60, P = 0.14) above baseline, respectively. CONCLUSIONS: INP induced increased foot arterial blood flow fluctuations compared to baseline. SPONSORSHIPS: The Norwegian Research Council provided funding to Otivio (grant: 241589).

Cardiac power parameters during hypovolemia, induced by the lower body negative pressure technique, in healthy volunteers.

BACKGROUND: Changes in cardiac power parameters incorporate changes in both aortic flow and blood pressure. We hypothesized that dynamic and non-dynamic cardiac power parameters would track hypovolemia better than equivalent flow- and pressure parameters, both during spontaneous breathing and non-invasive positive pressure ventilation (NPPV). METHODS: Fourteen healthy volunteers underwent lower body negative pressure (LBNP) of 0, -20, -40, -60 and -80 mmHg to simulate hypovolemia, both during spontaneous breathing and during NPPV. We recorded aortic flow using suprasternal ultrasound Doppler and blood pressure using Finometer, and calculated dynamic and non-dynamic parameters of cardiac power, flow and blood pressure. These were assessed on their association with LBNP-levels. RESULTS: Respiratory variation in peak aortic flow was the dynamic parameter most affected during spontaneous breathing increasing 103 % (p < 0.001) from baseline to LBNP -80 mmHg. Respiratory variation in pulse pressure was the most affected dynamic parameter during NPPV, increasing 119 % (p < 0.001) from baseline to LBNP -80 mmHg. The cardiac power integral was the most affected non-dynamic parameter falling 59 % (p < 0.001) from baseline to LBNP -80 mmHg during spontaneous breathing, and 68 % (p < 0.001) during NPPV. CONCLUSIONS: Dynamic cardiac power parameters were not better than dynamic flow- and pressure parameters at tracking hypovolemia, seemingly due to previously unknown variation in peripheral vascular resistance matching respiratory changes in hemodynamics. Of non-dynamic parameters, the power parameters track hypovolemia slightly better than equivalent flow parameters, and far better than equivalent pressure parameters.

Assessment of Right Ventricular Afterload in COPD.

BACKGROUND: We aimed to study whether pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) could be predicted by conventional echo Doppler and novel tissue Doppler imaging (TDI) in a population of chronic obstructive pulmonary disease (COPD) free of LV disease and co-morbidities. METHODS: Echocardiography and right heart catheterization was performed in 100 outpatients with COPD. By echocardiography the time-integral of the TDI index, right ventricular systolic velocity (RVSmVTI) and pulmonary acceleration-time (PAAcT) were measured and adjusted for heart rate. The COPD patients were randomly divided in a derivation (n = 50) and a validation cohort (n = 50). RESULTS: PH (mean pulmonary artery pressure (mPAP) ≥ 25mmHg) and elevated PVR ≥ 2Wood unit (WU) were predicted by satisfactory area under the curve for RVSmVTI of 0.93 and 0.93 and for PAAcT of 0.96 and 0.96, respectively. Both echo indices were 100% feasible, contrasting 84% feasibility for parameters relying on contrast enhanced tricuspid-regurgitation. RVSmVTI and PAAcT showed best correlations to invasive measured mPAP, but less so to PVR. PAAcT was accurate in 90- and 78% and RVSmVTI in 90- and 84% in the calculation of mPAP and PVR, respectively. CONCLUSIONS: Heart rate adjusted-PAAcT and RVSmVTI are simple and reproducible methods that correlate well with pulmonary artery pressure and PVR and showed high accuracy in detecting PH and increased PVR in patients with COPD. Taken into account the high feasibility of these two echo indices, they should be considered in the echocardiographic assessment of COPD patients.

Tissue oxygen saturation and finger perfusion index in central hypovolemia: influence of pain.

OBJECTIVES: Tissue oxygen saturation and peripheral perfusion index are proposed as early indirect markers of hypovolemia in trauma patients. Hypovolemia is associated with increased sympathetic nervous activity. However, many other stimuli, such as pain, also increase sympathetic activity. Since pain is often present in trauma patients, its effect on the indirect measures of hypovolemia needs to be clarified. The aim of this study was, therefore, to explore the effects of hypovolemia and pain on tissue oxygen saturation (measurement sites: cerebral, deltoid, forearm, and thenar) and finger photoplethysmographic perfusion index. DESIGN: Experimental study. SETTING: University hospital clinical circulation and research laboratory. SUBJECTS: Twenty healthy volunteers. INTERVENTIONS: Central hypovolemia was induced with lower body negative pressure (-60 mm Hg) and pain by the cold pressor test (ice water exposure). Interventions were performed in a 2×2 fashion with the combination of lower body negative pressure or not (normovolemia), and ice water or not (sham). Each subject was thus exposed to four experimental sequences, each lasting for 8 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements were averaged over 30 seconds. For each person and sequence, the minimal value was analyzed. Tissue oxygenation in all measurement sites and finger perfusion index were reduced during hypovolemia/sham compared with normovolemia/sham. Tissue oxygen saturation (except cerebral) and perfusion index were reduced by pain during normovolemia. There was a larger reduction in tissue oxygenation (all measurement sites) and perfusion index during hypovolemia and pain than during normovolemia and pain. CONCLUSIONS: Pain (cold pressor test) reduces tissue oxygen saturation in all measurement sites (except cerebral) and perfusion index. In the presence of pain, tissue oxygen saturation and perfusion index are further reduced by hypovolemia (lower body negative pressure, -60 mm Hg). Thus, pain must be considered when evaluating tissue oxygen saturation and perfusion index as markers of hypovolemia in trauma patients.

Elevated arterial lactate concentrations early after coronary artery bypass grafting are associated with increased anaerobic metabolism in skeletal muscle.

OBJECTIVE: To assess the effect of coronary artery bypass grafting with cardiopulmonary bypass on muscle perfusion, oxygen extraction, and lactate release during postoperative rest and exercise. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Patients undergoing planned coronary artery bypass grafting. INTERVENTION: Knee-extensor exercise before and after coronary artery bypass grafting. MEASUREMENTS AND MAIN RESULTS: Femoral artery blood flow was measured with ultrasound. Femoral vein blood and arterial blood were sampled at rest and during light exercise and were analyzed for hemoglobin, lactate, oxygen saturation, and oxygen partial pressure. Fourteen patients were tested before and after surgery. The arterial lactate concentrations were increased after surgery, both at rest and during light exercise. Resting arterial lactate increased from 0.65 (0.5-0.8) to 1.0 (0.9-1.3) mmol/L (p=0.01) (median and interquartile range). Furthermore, lactate was released from the leg even during postoperative rest, and the release of lactate was increased during postoperative exercise. There were no significant differences between the preoperative and postoperative femoral artery blood flow. Femoral vein oxygen partial pressure was reduced significantly after surgery, indicating reduced muscle cell oxygen partial pressure. CONCLUSIONS: The patients had elevated anaerobic metabolism in skeletal muscle after surgery to compensate for anemia. Lactate was released from the leg into the general circulation during postoperative rest and exercise. The postoperatively reduced hemoglobin concentration of 11.4 mg/dL (10.6-12.3) resulted in increased anaerobic metabolism and release of lactate from skeletal muscle. The authors concluded that coronary artery bypass grafting patients are susceptible to anaerobic metabolism even with maintained peripheral blood flow.

Impaired vascular function among young users of anabolic-androgenic steroids.

Supraphysiological doses of anabolic-androgenic steroids (AAS) is popular among recreational weightlifters and bodybuilders due to the performance-enhancing properties but is also associated with adverse cardiovascular effects. The knowledge about how AAS affect the vasculature is limited, although results from previous studies suggest alterations in vasoreactivity and morphology. In the present study we investigate the association between long-term use of AAS and vascular function. Hundred and twenty-three males were included in the study, 56 of them current AAS users and 67 weightlifting controls. Vascular function was evaluated by carotid artery reactivity and flow-mediated dilation. AAS users had significantly reduced carotid artery reactivity (p < 0.001) and flow-mediated dilation (p < 0.001) compared to weightlifting controls. Results from the present study indicate that long-term use of AAS affect the cardiovascular system negatively, measured as reduced carotid artery reactivity and flow-mediated dilation. These findings could partly explain sudden cardiovascular events among young long-term users of AAS.

Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

BACKGROUND: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. METHODS: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. RESULTS: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). CONCLUSION: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Nine treatments of 1000 mL therapeutic phlebotomy in a subject with polycythemia: A case report.

Large-volume therapeutic phlebotomy is the mainstay of hemochromatosis treatment and offers an opportunity to investigate the hemodynamic changes during acute hypovolemia. An otherwise healthy 64-year-old male with hemochromatosis participated. On nine separate visits, 1000 mL therapeutic phlebotomy was performed. On one occasion, pre- and post-phlebotomy orthostatic challenge with 27° reverse Trendelenburg position was administered. Mean arterial pressure, heart rate, and stroke volume were measured continuously during the procedures. The patient's tolerance to the interventions was continuously evaluated. The procedures were well tolerated by the patient. Mean arterial pressure was maintained during hemorrhage and following phlebotomy in both supine and reverse Trendelenburg positions, primarily through an increase in heart rate and systemic vascular resistance. The present study found that 1000 mL therapeutic phlebotomy in a patient with hemochromatosis may be acceptably and safely used to model hemorrhage. The approach demonstrates high clinical applicability and ethically robustness in comparison with volunteer studies.

Off-label use of clomiphene citrate to treat anabolic androgenic steroid induced hypogonadism upon cessation among men (CloTASH) - A pilot study protocol.

Background: Non-prescribed anabolic androgenic steroid (AAS) use is associated with AAS-induced hypogonadism (ASIH), and metabolic, cardiovascular, and mental health risks. Symptoms of ASIH (fatigue, depression, anxiety, sexual dysfunction) are hard to endure following cessation, but there is no consensus on whether endocrine treatment should be used to treat ASIH. This proof-of-concept study aims to explore safety of off-label clomiphene citrate therapy, whether the treatment will reduce the symptoms of androgen deficiency, and to study changes in health risks after cessation. Methods: In this open-labeled non-randomized off-label hormone intervention pilot study, we shall include males with AAS dependence intending to cease use. The 16-week intervention included clomiphene citrate, transdermal testosterone gel for the first four weeks and optional human chorionic gonadotropin (hCG) from week 4 if low treatment response. Measures of physical and mental health will be examined from ongoing AAS use, during the intervention, and at 6- and 12 months post cessation. Change in self-reported symptoms of hypogonadism and other withdrawal symptoms will be compared with data from a group of men who ended AAS use temporarily without the medical intervention. The study may provide valuable clinical insights and may be used to inform the design of future intervention studies.