A coronary angiography-derived index of microvascular resistance (caIMR) is proposed for physiological assessment of microvasular diseases in coronary circulation. The aim of the study is to assess diagnostic performance of caIMR, using wire-derived index of microvascular resistance (IMR) as the reference standard. IMR was demonstrated in 56 patients (57 vessels) with stable/unstable angina pectoris and no obstructive coronary arteries in three centers using the Certus pressure wire. Based on the aortic pressure wave and coronary angiograms from two projections, the caIMR was computed and assessed in blinded fashion against the IMR at an independent core laboratory. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the caIMR with a cutoff value of 25 were 84.2% (95% CI: 72.1% to 92.5%), 86.1% (95% CI: 70.5% to 95.3%), 81.0% (95% CI: 58.1% to 94.6%), 88.6% (95% CI: 76.1% to 95.0%), and 77.3% (95% CI: 59.5% to 88.7%) against the IMR with a cutoff value of 25. The receiver-operating curve had area under the curve of 0.919 and the correlation coefficient equaled to 0.746 between caIMR and wire-derived IMR. Hence, caIMR could eliminate the need of a pressure wire, reduce technical error, and potentially increase adoption of physiological assessment of microvascular diseases in patients with ischemic heart disease. Microvascular diseases have recently shown an increase in importance for the diagnosis and management of patients with chronic coronary syndrome . The patPhysiological parameters, fractional flow reserve (FFR)  and adenThe objective of the study is to evaluate diagnostic performance of the caIMR using wire-derived IMR as the reference standard. This study retrospectively analyzed patients with stable/unstable angina pectoris and no obstructive coronary arteries in three hospitals at Beijing, China. The computed caIMR was compared with the measured IMR in these patients. The significance and implications of the study were discussed relevant to adenosine-free indexes of coronary physiology.Based on the aortic pressure wave and coronary angiograms from two projections, a novel physiological parameter, caIMR (unit: mmHg⋅s/mm), is proposed as follows:L is a constant  that mimics the length from the inlet to the distal position , (Pd)hyp is the mean pressure (unit: mmHg) at the distal position at the maximal hyperemia, Vdiastole is the mean flow velocity (unit: mm/s) at the distal position at diastole, and K is a constant (K = 2.1) obtained from a previous literature (Vhyp = K⋅Vdiastole refers to the mean flow velocity (unit: mm/s) at the distal position at the maximal hyperemia, as shown in L position. The detailed theoretical derivation is described in the where terature  and VhypThe retrospective trial was demonstrated to assess diagnostic performance  of the caIMR in the FlashAngio system . The retrospective clinical trial was approved by the Institutional Review Boards (IRB) in Beijing Hospital, PLA General Hospital and Peking University First Hospital at Beijing, China, which conforms the declaration of Helsinki and Good Clinical Practice Guidelines of the China Food and Drug Administration. Written consent was waived owing to the minimal patient risk in accordance with the relevant guidelines and regulations of the IRB from the three centers.2); had known severe coagulopathy or bleeding disorders; were allergic to iodine contrast agents, adenosine or ATP. Angiographic exclusion criteria included poor contrast opacification, severe vascular overlap or distortion of the interrogated vessel, or when poor angiographic image quality precluded contour detection required by the FLASH software.Patients (aged at least 18 years) with stable or unstable angina pectoris and no obstructive coronary arteries by angiographic visual estimation  were enrolled in Beijing Hospital, PLA General Hospital and Peking University First Hospital at Beijing, China. Participants were excluded if they had suffered myocardial infarction within previous 7 days; had left ventricular ejection fraction ≤ 50%; estimated glomerular filtration rate (eGFR) < 45 ml/min hyp, is determined using the mathematical formula in the Appendix of a previous study  was determined automatically by the FlashAngio software, similar to a previous study hyp] along meshed coronary arteries from the inlet to the distal position  and (Pd)hyp = (Pa)hyp−(ΔP)hyp. The caIMR was computed in equation [1] by some researchers in an independent core lab blinded to the wire-derived IMR measurement.We have developed a specially designed CFD model to carry out the steady-state laminar flow simulation across the stenotic blood vessel in 10–30 s , which imn), thermodilution curves were obtained by at least 3 injections of 3–4 ml of 4o C saline during sustained hyperemia. Performance of the wire-derived IMR measurement was according to the standard procedures suggested by the RadiAnalyzer Xpress instrument . Moreover, examination of pressure drift was carried out through a pull-out of the pressure wire to the guiding catheter tip, where the ratio of (wire-derived mean pressure)/MAP should be between 0.97 and 1.03.A Certus pressure wire  was inserted to the distal position  by interventional cardiologists. Intracoronary nitrate (100 μg) was administered before physiological measurements. Hyperemic blood flow was induced by IV administration of adenosine-5′-triphosphate (ATP) at ≥140 μg/kg/min. To derive mean transit time  or percentage with counts. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)  of the cWire-derived IMR and caIMR were successfully demonstrated in 56 patients (57 vessels) with no obstructive coronary arteries at the age of 61.9 ± 9.2 years . Baseline patient characteristics are presented in This retrospective study assessed the caIMR against the wire-derived IMR in 56 patients (57 vessels). We reported that caIMR  showed the correlation coefficient of R = 0.746 (receiver-operating characteristic AUC of 0.919) with wire-derived IMR  in patients with stable/unstable angina pectoris and no obstructive coronary arteries.Vhyp = K⋅Vdiastole and K≈ 2.1 obtained from Table T10 in a previous study . Patients have undergone successful PCI but continue to have angina, patients with acute coronary syndrome, and patients after heart transplantation should be considered in the following studies. On the other hand, patients with vascular reactivity related to abnormalities in endothelial function (vasospastic angina) were recommended to take the intracoronary acetylcholine test .The retrospective study only included 56 patients (57 vessels) to test the proposed caIMR. The sample size was relatively small. We also used the measured aortic pressure wave during the wire-derived IMR measurement. There were some discordances between caIMR and IMR. IMR was measured in the maximal hyperemia while caIMR was computed based on the angiography-derived diastolic flow velocity in the contrast-induced sub-hyperemia, which is the main reason for the discordances between caIMR and IMR. A comparison of FFR  and iFR (WTP period of the diastole at the baseline) has shown some discordances, but iFR showed a non-inferior revascularization strategy to the FFR with respect to the rate of major adverse cardiac events at ≥12 months. This study is still at an early stage of development in angiography-derived microvascular diagnosis and no outcome studies have been performed. The following prospective study in multiple centers should be demonstrated to compare the rates of major adverse cardiac events at ≥12 months between caIMR and IMR in a large cohort of patients when the aortic pressure is measured by using a specialized pressure transducer  connected to the guiding catheter to record the aortic pressure wave during the entire procedure. A combination of caFFR  and caIMA novel parameter, caIMR, was proposed to characterize physiological impact of the microcirculatory dysfunction. There is correlation coefficient of R = 0.746 between caIMR and wire-derived IMR in patients with INOCA. The caIMR for physiological assessment of the microvascular diseases could provide important insights to patients with IHDs, which requires further investigations.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the retrospective clinical trial was approved by the Institutional Review Board (IRB) in Beijing Hospital, PLA General Hospital and Peking University First Hospital, which conforms the declaration of Helsinki and Good Clinical Practice Guidelines of the China Food and Drug Administration. The patients/participants provided their written informed consent to participate in this study.HA, H-PZ, BZ, QJ, FS, and YC performed the experimental measurement. YF and YG performed the theoretical analysis. YLH drafted the manuscript. YLH, JL, and YH reviewed the manuscript. All authors contributed to the article and approved the submitted version.YH holds stocks of Rainmed Ltd., Suzhou, China. HA is supported by the Beijing Hospital Clinical Research 121 Project (BJ-2019-193); and there is nothing to disclose for others.


Sexual dysfunction is a common problem in patients with chronic kidney disease. Disturbances in sexual function are noticed in early stages of chronic kidney diseases and deteriorate further as renal function declines. This is due to uremic effects, comorbid illness, anemia, hormonal disturbances, autonomic neuropathy, vascular diseases, hyperparathyroidism, hyperprolactinemia, side effects of medications, and psychosocial factors.This is a cross-sectional study which included 59 male patients who underwent renal transplantation for more than 6 months. The International Index of Erectile Function (IIEF-5) was adopted in our study to record the erectile function.The mean age was 49.41 years, and the mean number of hemodialysis per month was 5.31. The cause of the chronic kidney disease was diabetes mellitus in 35.59%, glomerulonephritis in 20.34%, and hypertension in 16.95%, other causes were diagnosed in order of decreasing frequency. Most patients developed improvement in the erectile function after transplantation. There was significant correlation with 3 of the elements of the IIFE-5.i.e; penile hardness pre-penetration, Maintaining erection during intercourse, and Difficulty to maintain erection to complete the intercourse  respectively, and the overall improvement after transplantation which showed a p-value of less than 0.031, while there was no significant correlation with Confidence with erection and Satisfaction with intercourse before and after transplantation  respectively. One of the patients (1.7%) developed severe dysfunction after that.ED is common sequel of chronic kidney disease. The etiology is multifactorial and may be worsen by advanced age, presence of diabetes mellitus and prolonged duration of hemodialysis. Renal transplantation has a positive impact on sexual function and lead to improvement of erectile dysfunction. Erectile dysfunction that persists after kidney transplantation is usually attributed to multiple preexisting comorbidities. •Sexual dysfunction is a common problem in patients with chronic kidney disease.•The etiology of Sexual dysfunction is multifactorial.•Renal transplantation has a positive impact on sexual function. Disturbances in sexual function are noticed in early stages of CKD and deteriorate further as renal function declines ,2.Sexual dysfunction has a major impact on the quality of life and it had been reported in both male and female patients with CKD. This greatly affects the social and the marital life of the affected patients .Seventy percent of males have some forms of erectile dysfunctions (ED) during their life time. Other reported sexual problems may include reduced libido, difficulty in achieving orgasm and anejaculation .The etiology of SD is often multifactorial, besides the uremic effects, factors such as comorbid illness, anemia, hormonal disturbances, autonomic neuropathy, vascular diseases, hyperparathyroidism, hyperprolactinemia, side effects of medications, and psychosocial factors all contribute to the existence of SD ,2.Renal transplantation prolongs life and improves the quality of life in patients with CKD. Because of normalization of the hormonal disturbances, renal transplantation improves the sexual health (e.g. libido), energy, and fertility .However, after kidney transplantation, the prevalence of SD still remains 46% in both men and women. The persistence of SD after receiving a kidney transplant may have a negative impact on the patients’ well-being .1.1scientific.research@duhokhealth.org.Ethical committee approval granted from the Duhok Directorate of General Health, Scientific Research Division, and email: 5277.The research is registered according the World Medical Association's Declaration of Helsinki 2013 at the research registry at the 13th of December 2019, Research registry UIN: research registry 1.2The aim of the study is to assess the erectile dysfunction in male patients before and after kidney transplantation by means of a validated, self-administered questionnaire.1.3This is a cross-sectional study which included 68 male patients who underwent renal transplantation for more than 6 months, patients with stable graft function were included. All were male patients aged 40 years or older and who attended regular visits to the transplantation clinic in Duhok kidney transplantation center from January 2018 to march 2019 were considered eligible and were included in this study.A translated questionnaire to the native local language from the original version of five items of the International Index of Erectile Function (IIEF-5) which was adopted in our study.Patients were given the questionnaire to answer it at home, data were collected before the transplantation and after transplantation.1.4ED is defined as the inability to achieve or maintain an erection sufficient to allow satisfactory sexual intercourse. Scoring for each item was done from 0 to 5. The total score ranges from 0 to 25 points, and the cutoff points proposed by the authors are as follow: severe dysfunction when the score ranges between 0 and 7, moderate dysfunction when the score ranges between 8 and 11, mild-to-moderate dysfunction score ranges between 12 and 16, mild dysfunction between 17 and 21, and no dysfunction between 22 and 25. Erectile dysfunction is defined as an IIEF-5 score of less than 22.The statistical calculations were done in Statistical Package for Social Sciences (SPSS 25:00 IBM: USA).The descriptive purposes of our study is displayed in frequency and percentages for categorical data and mean and standard deviation for continuous variables.Correlation were done using the two-tailed t-tests with 95% confidence interval, P values less than 0.05 were considered significant.The work of this article has been reported in line with the STROCSS criteria .2Our study included 59 kidney transplant male patients, their mean age was 49.41 years, and the mean number of hemodialysis per month was 5.31, The most cause of the chronic kidney disease was diabetes mellitus in 35.59%, followed by glomerulonephritis in 20.34%, hypertension in 16.95% of patients, and other causes were diagnosed in order of decreasing frequency, Most patients developed improvement in the erectile function after transplantation, there was a significant correlation with three of the elements of the IIFE-5 and the overall improvement after transplantation, The majority of patients had mild dysfunction before transplantation according to the IIEF-5 score, while after transplantation the majority of them reported a noticeable improvement, while one of the patients developed severe dysfunction, 3Erectile dysfunction is defined by the National Institute of Health (NIH) Consensus Development Conference as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. Although laboratory based diagnostic procedures are available, it has been proposed that sexual function is best assessed in a naturalistic setting with patient self-reporting technique .Renal failure is a major risk for erectile dysfunction and about half of patients with chronic renal failure may be impotent which is multifactorial but primarily organic. In addition to the uremic milieu, peripheral neuropathy, autonomic insufficiency, peripheral vascular disease and pharmacotherapy, all play an important role in the development of erectile dysfunction .Our study showed that ED is more common and more severe among patients aged 45 years and in those with history of hemodialysis. Increased age is a well-known risk factor for ED, the importance of increased age on the prevalence of ED in the renal transplant population has been verified in several studies, Malavaud et al., and his colleagues studied 271 kidney transplant patients, they found that the average age of those patients with ED was 49.2 years while those without ED was 44.5 years. They also found that ED is 3–4 times more likely to occur in those who are over 40 years old .The most common cause of CKD in our study was diabetes mellitus, diabetes mellitus is also a major cause of ED. This is multifactorial and is thought to be caused by acceleration of angiopathy and neuropathy. Long duration of hemodialysis is also a major risk factor for ED. This has been attributed to permanent damage of cavernous vessels and smooth muscles sustained during the long course of renal failure ,23.Early transplantation is recommended because it is more effective with lower costs than hemodialysis. Maintaining erectile function should be another reason for early transplantation.Regarding the role of kidney transplantation on sexual function, we found that majority of participant had improved ED post transplantation. There was significant correlation with 3 of the elements of the IIFE-5.i.e; penile hardness pre-penetration, Maintaining erection during intercourse, and Difficulty to maintain erection to complete the intercourse  respectively, and the overall improvement after transplantation which showed a p-value of less than 0.031, while there was no significant correlation with Confidence with erection and Satisfaction with intercourse before and after transplantation  respectively. One of the patients (1.7%) developed severe dysfunction after that. Improvement of sexual function after kidney transplantation has been reported in several similar studies supporting our results .In another more recent study of CKD patients receiving a spectrum of treatment such as peritoneal, hemodialysis, and renal transplant; renal transplant patients showed the most statistically significant increase in IIEF score ,28.In addition to the normalization of hormonal and metabolic functions post-transplant, there is a significant improvement of the psychosocial parameters in transplant recipients, which have a major impact on the sexual function as well. It is important to note that many patients have a persistent ED post-transplant, this is probably due to the fact that transplant alone cannot eliminate all comorbidities affecting both renal and erectile functions ,29,30.There was no significant association between ED and the use of different types of medications in this study, this result was comparable to other study in this regard .The author is the source of the funding.Not commissioned, externally peer reviewed..No conflict of interest is present to be declared


The SBP and DBP were ≥ 130 mmHg and ≥ 80 mmHg in 10,809 (48.52%) and 11,583 (51.99%) participants, respectively. During a median 6.2 years, 1271 cardiovascular events, 201 ESRD incidents, and 1061 deaths were noted. Individuals with SBP ≥ 130 mmHg and DBP ≥ 80 mmHg had higher hazards of hypertension-related adverse outcomes compared to the references (SBP 120–129 mmHg and DBP 70–79 mmHg). SBP < 100 mmHg was associated with hazards of all-cause death, and composite of ESRD and all-cause death during follow-up only among the antihypertensive medication users suggesting that the BP should be < 130/80 mmHg and the SBP should not be < 100 mmHg with antihypertensive agents to prevent the adverse outcome risk of insufficient and excessive antihypertensive treatment in CKD patients.The effect of blood pressure (BP) on the incident cardiovascular events, progression to end-stage renal disease (ESRD) and mortality were evaluated among chronic kidney disease (CKD) patients with and without antihypertensive treatment. This nationwide study used the Korean National Health Insurance Service-Health Screening Cohort data. The hazards of outcomes were analysed according to the systolic BP (SBP) or diastolic BP (DBP) among adults (aged ≥ 40 years) with CKD and without previous cardiovascular disease or ESRD ( Hypertension is commonly accompanied by CKD and an important modifiable risk factor for cardiovascular events and CKD progression3. Therefore, controlling the blood pressure (BP) within an optimal range is a major public health priority and an important clinical concern for a patient with CKD.Chronic kidney disease (CKD) is a major public health concern closely related to the risk of cardiovascular disease, progression to end-stage renal disease (ESRD), and premature mortality13, a definite consensus has not been achieved15 even in more recently released guidelines including the 2017 American Heart Association/American College of Cardiology (AHA/ACC)12 and the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH)13 guidelines for managing hypertension. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends BP ≤ 140/90 mmHg for CKD patients with urine albumin excretion rate < 30 mg/24 h and ≤ 130/80 mmHg for CKD patients with moderately or severely increased albuminuria5. Although these recommendations have been accepted as reasonable, the supporting evidence was considered to be insufficient15. In contrast, the Eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8)10 recommended BP < 140/90 mmHg for hypertensive adults with CKD, and the target BP did not vary according to the albuminuria status. In contrast, among individuals at high risk for cardiovascular events but without diabetes from the Systolic Blood Pressure Intervention Trial (SPRINT), targeting a systolic BP (SBP) < 120 mmHg, compared with < 140 mmHg, was associated with lower rates of major cardiovascular events and death from any cause, and no significant effect modification was observed according to the presence of CKD11. However, the lower limit of the BP target was not clearly defined. Furthermore, outcome trials or large-scale observational studies that evaluated an optimal BP target for CKD populations are extremely limited in Asia16.Although reports including observational studies, clinical trials, and clinical practice guidelines, attempted to establish an optimal BP target among the CKD patientsTherefore, to identify the optimal BP in patients with CKD with respect to the risk of hypertension-related adverse outcomes, we aimed to (1) assess the distribution of BP levels and (2) compare the hazards of composite of progression to ESRD and all-cause death (primary outcome); all-cause death, and compositive of cardiovascular events and ESRD (secondary outcomes) during follow-up according to the baseline BP ranges among the individuals with CKD using the Korean National Health Insurance Service (KNHIS) database.2 for the total population, and 5.9% of the population showed urine dipstick positivity for protein. The mean age, proportion of women, proportion of individuals with low-income status, prevalence of dyslipidaemia and diabetes mellitus (DM), and eGFR were higher among the users than among the non-users.The study included 22,278 participants Fig. . Among tOf the 22,278 (100%) participants, 4360 (19.6%) had an SBP ≥ 140 mmHg, and 10,809 (48.5%) had an SBP ≥ 130 mmHg. A total of 3016 (13.5%) participants had a diastolic BP (DBP) ≥ 90 mmHg, while 11,583 (52.0%) had a DBP ≥ 80 mmHg. Furthermore, of the 10,104 (100%) users of antihypertensive medications, 2703 (26.8%) had an SBP ≥ 140 mmHg, while 5920 (58.6%) had an SBP ≥ 130 mmHg. When the distribution of DBP was assessed among the antihypertensive users, the DBP was ≥ 90 mmHg in 1728 (17.1%) and ≥ 80 mmHg in 5792 (57.3%) users.During a median follow-up of 6.2 (interquartile range: 5.6–6.5) years, 1225 primary outcomes  were observed. Individually, 1271 cardiovascular events, 201 incident ESRD cases, and 1061 all-cause deaths were noted. The hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary and secondary outcomes are presented according to the prespecified SBP categories Tables . When thThe HRs (95% CIs) of primary and secondary outcomes were presented according to the prespecified DBP categories Table . CompareIn this nationwide population-based longitudinal study, including 22,278 participants with CKD, an SBP ≥ 130 mmHg was associated with significantly higher hazards of hypertension-related adverse outcomes compared with the reference range of 120–129 mmHg, while a DBP ≥ 80 mmHg was associated with higher hazards of hypertension-related adverse outcomes compared with the reference range of 70–79 mmHg. Nevertheless, approximately half of the participants exhibited an SBP ≥ 130 mmHg and DBP ≥ 80 mmHg. Among the antihypertensive medication users, an SBP < 100 mmHg was associated with a significant increase in the hazards of all-cause death, and composite of ESRD and all-cause death during follow-up.To the best of our knowledge, this is the first study to evaluate the distribution of the SBP and DBP in a large-scale nationwide population with CKD in Asia. In this study, the SBP was ≥ 140 mmHg in 19.6% of the participants, and the DBP was ≥ 90 mmHg in 13.5% of the participants. When the distribution of the BP was evaluated among antihypertensive medication users only, 26.8% of the patients had an SBP ≥ 140 mmHg, while 17.1% had a DBP ≥ 90 mmHg. When the threshold BP was changed to 130/80 mmHg, almost half (48.5%) of the total participants showed an SBP ≥ 130 mmHg, and more than half (52.0%) exhibited a DBP ≥ 80 mmHg. The SBP was ≥ 130 mmHg in almost 60% of the antihypertensive medication users, and the DBP was ≥ 80 mmHg in a similar proportion of the antihypertensive medication users. These results suggest that the BP control status may be insufficient in a substantial proportion of the patients with CKD.11. However, a definite consensus was not achieved, even among the clinical practice guidelines10. Recently, the SPRINT reported that an SBP target < 120 mmHg led to a decrease in the incidence of major cardiovascular events and death compared with an SBP < 140 mmHg among patients at high risk of cardiovascular events11. However, until recently, the extent to which the results from the SPRINT study should be applied to people with CKD, especially those with more progressed disease (eGFR < 45 ml/min/1.73 m2), is still under debate17. While the balance of risk and benefit of intensive BP control may differ across eGFR levels, the mean eGFR in the SPRINT participants with CKD was 48 ml/min/1.73 m211, which was more favourable than that in our study (41.7 ml/min/1.73 m2). A post hoc analysis of the SPRINT study suggested an attenuation of the cardiovascular benefit from intensive treatment with lower eGFR, and no apparent net benefit was observed among 891 participants with an eGFR of < 45 ml/min/1.73 m218. In our study, 24.5% of the participants had an eGFR < 30 ml/min/1.73 m2, and a BP ≥ 130/80 mmHg versus the reference range (120–129/70–79 mmHg) was associated with increased hazards of hypertension-related adverse outcomes, suggesting that the optimal BP range may be less than this level.Over the past few decades, several studies attempted to address the optimal target ranges of the BP in the CKD population19. In their study, the associations between the BP and adverse outcomes were linear or flat and then increasing among the non-users of antihypertensive agents but J-shaped among the active antihypertensive users. According to Jung et al.19, among the active users of antihypertensive agents, the risk for a composite of cardiovascular and renal outcomes increased in the individuals with SBP values < 115 mmHg and > 135 mmHg, and the risk for early all-cause death increased in those with SBP values < 125 mmHg and > 135 or 145 mmHg. Consistent with the results of a previous study, our study showed that the association of hazards for all-cause death, and composite of ESRD and all-cause death during follow-up with an SBP < 100 mmHg was found only among CKD patients using antihypertensive agents. These results suggest that an excessive BP lowering with antihypertensive medications may increase the risk of adverse outcomes also in individuals with CKD. The SBP cut-off was lower in the present study including only CKD patients (SBP < 100 mmHg) compared with that reported in a previous study including healthy individuals (SBP < 115–125 mmHg). Likewise, a J-shaped association of both the SBP and DBP with mortality has been reported for 651,749 U.S. veterans with CKD, and 53.7%, 49.7%, and 34.2% of them were taking renin–angiotensin–aldosterone system (RAS) inhibitors, beta-blockers, and calcium-channel blockers, respectively8. They reported that SBP of 140–160 mmHg and DBP of 80–90 mmHg were associated with best outcomes8 showing higher BP thresholds than our results. In their study8, patients with “ideal” BP (< 130/80 mmHg) demonstrated increased mortality rates possibly due to the inclusion of patients with low SBP and DBP. Another observational study including 2655 Japanese outpatients with CKD under nephrologist care showed that SBP < 110 mmHg and DBP < 70 mmHg increased risks of cardiovascular events and all-cause death20. However, these studies included only elderly veterans (mean age 73.8 years)8 or outpatients under nephrologist care from only 11 hospitals20. Moreover, both of these studies20 did not consider the possible differential impacts of BP on outcomes according to antihypertensive medication use.Here, an SBP < 100 mmHg was related to the hazards of all-cause death, and composite of ESRD and all-cause death during follow-up in patients treated with antihypertensive medications but not in individuals without antihypertensive therapy. Recently, Jung et al. reported different patterns of the association between the BP and adverse outcomes according to antihypertensive medication use in 492,540 Korean adults without pre-existing cardiorenal diseases23. In a study that compared statistical models that use simple summary measures of the repeat information on SBP (including baseline only and cumulative mean), against more complex methods that model the repeat information24, in comparison with the baseline-only model, modest benefits were observed using the cumulative mean of SBP, but any of the other complex methods demonstrated little further improvement. Fifth, CKD was defined only based on the eGFR; we could not reflect other features to characterise CKD, including albuminuria because except for the urine dipstick positivity for protein, the quantitative measures of albuminuria were not evaluated. Lastly, our study population consisted of Korean adults; thus, our results should be extrapolated to other ethnic groups with caution.There are several limitations of this study. First, although we tried to adjust for potential confounders, the effect of residual unmeasured confounders may remain. Second, BP measurement devices were heterogenous across institutions. However, quality assessments are applied to the BP measurement instruments in all health examination institutions according to the Basic Act on National Health Examination in Korea. Third, the present data did not include the ambulatory or home BP measurements. Fourth, categories of BP were defined based on BP measurements at a single timepoint. Repeated visit measurements and changes in BP during follow-up were not reflected due to the unavailability of the data in most of the participants. However, previous large epidemiological studies on the association between BP and adverse outcomes also utilized a single BP measurement to produce meaningful resultsOur study has major strengths, including a comparatively large nationwide population across a broad age spectrum, high rates of participation, standardised data collection methods, an adequate follow-up period, and availability of comprehensive possible confounding factors, which support the validity of our results. Stratified analysis according to the antihypertensive medication use provided insights on the effect of BP lowering with antihypertensive agents and lower limit of BP targets. Our results may provide suggestions on the BP targets for Asian CKD patients, which have been lacking in relevant evidence.This nationwide longitudinal population-based cohort study demonstrated that a BP ≥ 130/80 mmHg was associated with higher hazards of hypertension-related adverse outcomes compared with the reference range of 120–129/70–79 mmHg in adults with CKD. In approximately 50% of the Korean adults with CKD, SBP was ≥ 130 mmHg and DBP was ≥ 80 mmHg. Among the CKD patients using antihypertensive medications, those with an SBP < 100 mmHg showed higher hazards of all-cause death, and composite of ESRD and all-cause death during follow-up. These findings suggest that it would be appropriate to target the BP to < 130/80 mmHg and not to lower the SBP to < 100 mmHg with antihypertensive agents to prevent the risk of adverse outcomes associated with insufficient and excessive BP lowering among CKD patients aged ≥ 40 years. In this respect, the BP control status of Korean CKD patients need to be optimized. Further research is required to evaluate the optimal blood pressure target according to comorbidities and medications in patients with hypertension.The KNHIS-Health Screening Cohort (NHIS-HEALS) data from January 2002 to December 2015 were used in this study. Supplementary Appendix 2. The time-point of the examination conducted between 2009 and 2010 was considered as the baseline. The individuals with a history of myocardial infarction (MI) (ICD-10 codes I21–22), stroke (ICD-10 codes I63–64), heart failure (HF) (ICD-10 code I50), and/or ESRD at or before baseline, and those with malignancies (ICD-10 codes C00-C97) throughout the study period were excluded. The individuals who cannot be classified as users or non-users of antihypertensive medications and those with missing data for at least one variable were also excluded . Referring to the previous studies26, MI was identified as the recording of ICD-10 codes I21 or I22 during hospitalisation or claims made ≥ two times under those codes, while stroke was defined as the recording of ICD-10 codes I63 or I64 during hospitalisation with claims for brain magnetic resonance imaging or brain computed tomography. The hHF was defined as ≥ one hospitalisation under a primary diagnosis of ICD-10 code I50, as mentioned in the previous studies29. The study population was followed-up from baseline to the date of death, development of endpoint disease, or December 31, 2015, whichever came first.The primary outcome was the composite of ESRD and all-cause death during follow-up. The secondary outcomes were all-cause death, and composite of cardiovascular events and ESRD during follow-up. The individuals with ESRD were defined as (1) those with one or more claims under ICD-10 codes N18–19 and who underwent haemodialysis (≥ 90 days), peritoneal dialysis (≥ 90 days), or kidney transplantation and/or (2) those who have had the health insurance benefit of relieved Co-payment Policy in Korea for ESRD, which is a welfare system in Korea aimed at reducing the related medical expenses for registered patients with certain severe illnesses, including ESRD31. Blood tests were performed using venous samples drawn after overnight fasting. These health examinations were conducted only in hospitals certified by the KNHIS. The presence of DM and dyslipidaemia was defined according to a previous study26.Questionnaires were used to obtain information on the smoking status , alcohol consumption, and regular exercise. Definitions of heavy alcohol consumption, regular exercise, low income status, and body mass index (BMI) are summarized in supplementary Table During health examinations performed in hospitals certified by the KNHIS, the BP was measured by qualified medical personnel using sphygmomanometers or oscillometric devices at brachial levels after 5 min of rest in a sitting position.19. The individuals who had been prescribed with antihypertensive medications for ≥ 180 days in the previous year from the baseline were categorised as users. Non-users were defined as those who (1) had been prescribed with antihypertensive medications for < 90 days in the previous year from the baseline and (2) had not been prescribed any antihypertensive medications in the past 6 months from the baseline.The participants were stratified into two groups according to antihypertensive medication usep-values < 0.05 were considered significant. The baseline characteristics of the study population were analysed in the total population and among users and non-users of antihypertensive agents. The continuous variables were expressed as mean ± standard deviation, whereas the categorical variables were presented as frequencies and percentages.Statistical analyses were conducted using SAS software . Two-sided The incidence rates of outcomes were calculated as the number of incident cases divided by the follow-up duration (person-years). Multivariate Cox regression analyses were performed to calculate the HRs (95% CIs) for the outcome incidence according to the prespecified categories of baseline SBP or DBP. The prespecified SBP categories were < 100, 100–109, 110–119, 120–129, 130–139, 140–149, and ≥ 150 mmHg, while the DBP categories were < 60, 60–69, 70–79, 80–89, 90–99, and ≥ 100 mmHg. Regression models were adjusted for age, sex, current smoking, alcohol consumption, regular exercise, household income level, BMI, presence of dyslipidaemia, DM, and urine dipstick positivity for protein. Stratified analyses according to antihypertensive medication use were additionally performed.The data that support the findings of this study are available from the Korean National Health Insurance Service (KNHIS) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the KNHIS.Supplementary Information.


Aerobic exercise generates increased cardiorespiratory fitness, which results in a protective factor for cardiovascular disease. High-intensity interval training (HIIT) might produce higher increases on cardiorespiratory fitness in comparison with moderate-intensity continuous training (MICT); however, current evidence is not conclusive.To compare the effects of a low-volume HIIT and a MICT on maximal oxygen consumption (VO2max), systolic blood pressure, and diastolic blood pressure during eight weeks in healthy men between 18 and 44 years of age.We conducted a randomized controlled trial. Forty-four volunteers were randomized to HIIT (n=22) or MICT (n=22). Both groups performed 24 sessions on a treadmill. The HIIT group completed 15 bouts of 30 seconds , while the MICT group completed 40 minutes of continuous exercise (65-75% HRmax). The study is registered as a clinical trial via clinicaltrials.gov with identifier number: NCT02288403.Intra-group analysis showed an increase in VO2max of 3.5 ml/kg/min  in HIIT and 1.9 ml/kg/min  in MICT. However, the difference between the two groups was not statistically significant . MICT generated a greater reduction in systolic blood pressure compared to HIIT . No statistically significant differences were found between the groups for DBP.Results indicated no significant change in VO2max with a low-volume HIIT protocol versus MICT after 24 sessions. In contrast, MICT provided a greater reduction in systolic blood pressure compared to HIIT Some studies have shown that HIIT generated faster and more significant adaptations in VO2max when compared to MICT et al.High blood pressure is a common health condition that is associated with increases in the incidence of all-cause mortality and cardiovascular disease. Cornelissen, Therefore, the primary objective of this study was to compare the effect of a low-volume HIIT program versus a MICT program in VO2max among healthy men. The secondary objective was to identify the effect of both exercise programs on systolic and diastolic blood pressure. We hypothesize that those in the HIIT group would have significantly greater improvements in VO2max and BP responses compared to the MICT group.This two-arm randomized control trial with parallel groups was developed following the CONSORT statement for randomized trials of non- pharmacological treatment Universidad de Antioquia Research Ethics Committee approved all forms and study protocols.Participants were recruited via posters, word of mouth, social media, and email around the academic community of a public university in Medellín, Colombia. We asked men between 18 and 44 years of age who did not meet the physical activity recommendations of 150 minutes of aerobic exercise per week to participate. Those who responded and agreed to participate voluntarily in the study were asked to sign an informed consent form. The Individuals with any of the following characteristics were excluded from the study: Those who practiced HIIT, smoked, had a history of pulmonary, metabolic or cardiovascular disease, arrhythmias, heart failure, hypertension, diabetes mellitus, were being treated with anticoagulants, beta-blockers, calcium antagonists, bronchodilators, steroids, or had cognitive, sensory, neuromotor, and/or musculoskeletal disorders that could affect their participation in any of the study protocols. All subjects were evaluated by a sports medicine physician who authorized their participation in the study according to the criteria mentioned above.For the purpose of this study, we were interested in examining changes in maximal oxygen consumption (VO2max) in the two groups. We evaluated VO2max via a graded exercise test on a treadmill  using a portable gas analyzer .We were also interested in examining changes in both systolic blood pressure and diastolic blood pressure between the groups. Blood pressures was measured with an Omron M3 HEM-7200-E™  automatic blood pressure monitor.A detailed description of the study design along with specific details of the protocols utilized to measure the primary and secondary outcomes have been published elsewhere The MICT group was prescribed a 40-minute treadmill session at 65- 75% of maximal heart rate throughout the eight-week intervention. The HIIT group underwent 15 bouts of 30 seconds at 90-95% maximal heart rate followed by 60 seconds of recovery at an equivalent speed to achieve 50- 55 % of maximal oxygen consumption on a treadmill. In addition, they were encouraged to continue with their regular daily routines but were discouraged to engage in any other form of exercise. They were provided an Omron HJ- 112™  pedometer to monitor their daily ambulatory activity.We used the percentage of VO2max for recovery to determine an accurate speed during the recovery period for each participant considering that 60 seconds is not enough time for the heart rate to decrease and provide an accurate measurement of recovery. We considered using this method to provide a more accurate estimate of recovery intensity.A qualified trainer was present throughout each session to ensure participants reached and maintained the desired intensity. The speed of the treadmill was adjusted manually while the elevation was maintained constant at 10%. In addition, following their respective interventions, all participants preformed a resistance-training program three times per week following established guidelines To control selection bias and minimize confounding variables, a randomization sequence was generated through four- and six-size permuted blocks with a 1:1 ratio between the groups ,In order to determine appropriate sample size, a mean difference in VO2max of 3.5 ml/kg/min with standard deviations (SD) of 2.6 and 4.6 for the HIIT and MICT groups, respectively Intention-to-treat analyses were conducted for comparisons between groups. Also, sensitivity analyses  were completed for subjects who completed ≥70% of the training sessions. Normality, homoscedasticity, and linearity tests were considered as basic assumptions for the use of t tests and analysis of covariance (ANCOVA) The Mann-Whitney U test was adopted when the assumptions for parametric analyses could not be obtained; in this case, the values are reported in medians and interquartile ranges (IQR). Two-tailed statistical significance tests with a p<0.05 and a 95% confidence level (95% CI) were used. Multiple imputation techniques were applied to the management of missing data for VO2max, systolic blood pressure, and diastolic blood pressure Data were collected between March, 2015, and May, 2016. A total of 135 individuals who responded to our request to participate were evaluated. Of those who responded, 26 did not meet the selection criteria, three did not agree to participate, and 62 did not enter the study for other reasons (primarily due to time difficulties to comply with the sessions). The final sample consisted of 44 men distributed evenly between the HIIT and MICT groups  .Participant baseline characteristics are presented in 2max) between the HIIT and MICT groups (difference (Δ) 0.98 ml/kg/min; 95% CI -2.26 to 4.23, p=0.54)  while in the MICT group, the increase of this variable did not reach significance . When analyzing the VO2max changes individually, it was possible to identify that the participants of the HIIT group presented an average gain of 9.4% vs. 6.0% found in the subjects in the MICT protocol (p=0.67) with a positive intervention response of 81.8% in HIIT compared to 59% for MICT (p=0.09).After adjusting for baseline values, age, BMI, weight, and height there was no significant difference in the primary outcome (VO p=0.54) . VO2sub>In the per protocol analyses (those who completed ≥70% of the programmed training sessions), no differences were found in the primary outcome (VO2max) between groups post-training . In the intragroup analyses, statistically significant differences and important practical differences were found in both those who received the HIIT intervention , as well as in the MICT group .Systolic blood pressure and diastolic blood pressure values did not meet the assumption needed to utilize the ANCOVA test, therefore, the non- parametric Mann-Whitney U test was used. In the intention to treat analyses, a lower value of systolic blood pressure was found post-intervention in those in the MICT group ; median difference 8 mm Hg (p<0.001). In addition, no significant differences were found after eight-weeks in diastolic blood pressure between the groups ; median difference 0.2 mm Hg (p= 0.15) .In the intra-group analyses, no median differences were observed in systolic blood pressure for those who received the HIIT intervention , or in diastolic blood pressure . In the MICT group, systolic blood pressure was significantly reduced after the intervention ; median difference -1.7 mm Hg (p=0.02), while diastolic blood pressure did not change ; median difference 1.3 mm Hg (p=0.77).In the per protocol analyses, the post-intervention values of systolic blood pressure were lower in the MICT group compared to the HIIT group , whereas for the diastolic blood pressure, the differences did not achieve statistical or practical difference . In the intragroup analysis of the per protocol analyses, no statistically significant differences were found in the systolic blood pressure and diastolic blood pressure values .Training intensities were individually monitored and controlled by trained personnel who continuously supervised the heart rate monitor of each participant during the exercise sessions to guarantee compliance with the intensities for each load. The mean heart rate was determined to be 169.6 beats per minute, equivalent to 91.2% maximum heart rate.In total, five adverse events (three in the MICT group and two in the HIIT group) occurred during the interventions period, all of which affected the musculoskeletal system. The three events in the MICT group included one event of Hoffitis in the right knee not associated with training in this study, as it was the result of lifting a heavy object at home. The second event was muscle fatigue in the gastrocnemius associated with running on the treadmill, which improved by reducing the training load. The third event was a right medial ankle contusion not associated with the interventions, which occurred while the participant played soccer a day after finishing the training sessions and forced us to postpone the final evaluations for 12 days.In the HIIT group, there were two adverse events associated with the intervention. The first was right pes anserine bursitis due to training and associated with the inclination of the treadmill. The participant abandoned the intervention after 15 sessions because the symptoms did not improve, despite treatment with oral non-steroidal anti-inflammatories. The second event was tendinitis in the vastus medialis oblique in its insertion in the patella, which was associated with training on the treadmill. The participant partially improved after reducing the training load and medication with non-steroidal anti-inflammatory drugs.Regarding adherence, 18 individuals in the HIIT group and 19 in the MICT group  completed ≥70% of the planned sessions. It should be noted that 13 subjects in the HIIT group and 10 volunteers in the MICT group completed ≥ 90% of the sessions.,,Our main finding suggests that after adjusting for confounding variables, such as age, BMI, weight, height, and baseline VO2max, the HIIT protocol was not superior to the MICT protocol in improving the VO2max of this group of apparently healthy young men who engaged in physical activity for less tan 150 minutes/week. This finding is congruent with recent meta-analysis results from apparently healthy young adults reporting that HIIT-based interventions (regardless of their characteristics) did not improve significantly the performance with cardiorespiratory fitness compared to MICT protocols ,-metabolic equivalent of task, MET) is required for long-term reductions in mortality and morbidity ,,Conversely, from the practical and statistical points of view, those with health impairments, such as classic cardiovascular risk factors , coronary heart disease, and heart failure, the HIIT protocols have shown to be more advantageous than the MICT ones to increase VO2max, As it is well known, randomization aims at balancing and accounting for known and unknown factors that could affect the dependent variables; however, it cannot fully guarantee the identification of these factors, especially when sample sizes are small. Therefore, when there are differences between groups in some of the variables, as in this case, they should be adjusted in the final analyses It should be noted that the HIIT group had a baseline VO2max that was 3.0 ml/kg/min lower than the MICT group, which could explain the higher gain obtained by this group (+3.5 ml/kg/min) compared to the increase in the MICT group (+1.9 ml/kg/min). This finding is congruent with previous results revealing that HIIT has an apparent adaptive effect on VO2max in favor of less trained subjects In the intragroup analyses, the VO2max increase was clinically significant in the participants undergoing HIIT, as it changed from 39.2 ml/kg/min at baseline to 42.7 ml/kg/min at the end of the intervention. This finding is similar to that in other studies, which show that a HIIT program improves aerobic power in young, sedentary adults after two and eight weeks of training ,,,,The improvement in VO2max among those who completed HIIT could be explained by central adaptations including increases in systolic volume and cardiac output, as well as peripheral changes In regards to the secondary outcome, a lower systolic blood pressure was found in individuals who received the MICT intervention, a difference that achieved statistical and clinical significance. It is worth noting that systolic blood pressure in the HIIT group increased by 3.8 mm Hg compared to its initial value, whereas the MICT group systolic blood pressure was reduced by 1.7 mm Hg from baseline. These changes explain the difference in blood pressures between the groups. Our findings disagree with previous data about the benefits attributed to aerobic exercise, as both HIIT and MICT contributed to the reduction of systolic blood pressure and diastolic blood pressure with higher decreases in hypertensive individuals ,Nonetheless, no physiological explanations can be provided by the authors to support the increase in systolic blood pressure in the HIIT group other than coincidence, as all the evaluations were performed at the same time of day, under equal conditions, and following the same protocols. This finding differs from that reported in two meta-analyses involving people with cardiovascular risk factors in which no differences in systolic blood pressure were found in those trained with HIIT vs. MICT On the other hand, there is evidence indicating that to improve vascular function, the long-duration HIIT is more effective than the short-duration training et al.et al.’s For diastolic blood pressure, no differences were found between the groups after the intervention or when the baseline and post-intervention values were compared within each of the groups. These results are partially consistent with those found in the meta-analysis by Ramos, et al.While we applied the stimulus with the strength protocol in both groups as a non-differential co-intervention, it is possible that it had some influence on the effect of VO2max, as well as systolic blood pressure and diastolic blood pressure. However, according to the results presented by Buckley, The practical justification for having the strength component in both intervention protocols lies in the need to include strength exercises as a fundamental part of any holistically oriented physical activity program given the importance of incorporating physical fitness, cardiorespiratory endurance, muscular strength, and endurance in exercise intervention programs. Thus, our study focused on improving not only cardiovascular health, but also musculoskeletal health in apparently healthy adults A familiarization period before the intervention protocol may be beneficial in reducing the adverse effects of exercise training. Although our study only reported a total of five incidents in the groups, it would be beneficial to reduce such events. The familiarization period could help individuals adjust to the demand of the different loads, given the subjects’ low level of physical activity.Besides the methodological design used , the main strength of our study was conducting the training sessions in an individualized manner and under the constant supervision of a qualified trainer. Nevertheless, our study is not without limitations: Firstly, we could not control the participants’ physical activity levels beyond the research interventions, which may have affected the variations in VO2max from baseline values and hindered the detection of possible differences between the two groups. Although the volunteers were given a pedometer to monitor their physical activity, it was not possible to record the steps in all of the participants. Another limitation was not using the VO2max baseline values as an inclusion criterion for the volunteers. Although the level of physical activity was used as an inclusion criterion through the Global Physical Activity Questionnaire (GPAQ), some of the individuals who were randomly assigned to the MICT group had VO2max baseline values above the average among subjects with low physical activity levels according to age. Given the characteristics of the interventions in both arms of our study, based on exercise sessions with a group of volunteers exercising at moderate intensity and another group at high intensity, it was difficult to blind participants to the interventions. Finally, we should note that the sample size was calculated with an 80% power.et al.’s et al.et al.In summary, the results of this randomized clinical trial do not allow us to affirm that HIIT is superior to MICT for increasing VO2max in healthy 18 to 44-year-old men or vice versa. However, it may be said, as in Milanovic,


Background: Severe eosinophilic asthma decreases lung function and causes worsen symptoms, often forcing recurrent maintenance corticosteroid use. The aim of our real-life study was to evaluate the effectiveness of an add-on treatment with benralizumab in patients with severe eosinophilic asthma, paying particular attention to the impact on their quality of life (QoL).Materials and methods: In this prospective study, 10 outpatients with severe eosinophilic asthma were added-on with benralizumab and followed-up in our severe asthma clinic after 12 and 24 weeks. At each patient visit, pre-bronchodilator FEV1 and inflammatory markers were recorded. Variations in asthma symptoms control and QoL perception was assessed by validated questionnaires.Results: All the subjects experienced a marked reduction of nocturnal and diurnal symptoms over time and were able to stop using OCS, as documented by the improvement in Asthma control test (ACT) and Asthma Control Questionnaire score. Similarly, we recorded a statistically significant increase in patient’s QoL perception in EQ-VAS, EQ-5D-3L and Asthma Quality of Life Questionnaire (AQLQ) assessment (p < 0.05). Simultaneously we recorded a significant reduction in eosinophilic inflammation, an improvement in pre-bronchodilator FEV1. These results appear to be in line with those already obtained in the previous randomized controlled trials (RCTs).Conclusion: Our 24-weeks real life experience supports the effectiveness of an add-on treatment with benralizumab in reducing eosinophilic inflammation and OCS-use, increasing lung function and improving control of nocturnal and diurnal symptoms, as well as restoring severe asthma patients to a better QoL. As a reRecent available OCS-sparing biological therapies for severe eosinophilic asthma are increasingly showing efficacy in terms of asthma control and enhanced quality of life . Among t1 and symptom control compared to placebo, especially in patients with more than 300 blood eosinophils/microliter in the pre-treatment period.The approval of benralizumab in the treatment of severe refractory eosinophilic asthma is based on the results of the WINDWARD program, which includes the two phase III studies on exacerbations, SIROCCO  and CALIOutside of these randomized clinical trials (RCT), in recent times, real life studies on benralizumab effectiveness have been gaining increasing interest . Indeed,On this background, the aim of this preliminary study was to present our real-life experience. As GINA Difficult to Treat and Severe asthma guidelines  recommen3 of peripheral blood. Patients were excluded from the study if they were not completely adherent to their asthma maintenance prescribed therapy, showed an incorrect inhaler technique or if they had any other overlapping pulmonary condition  likely to interfere with results. This study was carried out according to the principles of the Declaration of Helsinki, was approved by the local ethics committee , and all recruited patients gave their written informed consent.In this prospective observational real-life study, we enrolled 10 consecutive outpatients with diagnosis of severe eosinophilic asthma . InclusiBenralizumab was prescribed at the licensed dose of subcutaneous 30 mg according to the approved posology of a single subcutaneous injection, to be administered at intervals of 4 weeks for the first three times, and every 8 weeks thereafter. Each drug administration was performed in our outpatient clinic and patients were observed for at least an hour to record any immediate adverse reaction.All the 10 patients included in the study, have been visited at baseline and after 12 and 24 weeks after starting treatment. At each patient visit the following parameters were recorded and comparatively evaluated: pre-bronchodilator forced expiratory volume in 1 s (FEV1), blood eosinophil count, number of exacerbations during the previous 24 weeks, fractional exhaled nitric oxide (FeNO), asthma control test (ACT) score, six items Asthma Control Questionnaire (ACQ-6) score, Asthma Quality of Life Questionnaire (AQLQ) score, EuroQol-Visual Analogue Scales (EQ-VAS) score, EuroQol-5Dimensions-3Levels (EQ-5D-3L) assessment and Beck Depression Inventory score (Beck DI). The doctor made his judgment on the clinical course of asthma by assigning a GETE  score. Moreover, all enrolled patients were carefully checked in order to timely detect the eventual onset of side effects and adverse events.ACT  includesThe ACQ-6  is calcuThe AQLQ  is calcuEQ-VAS  is a verThe EQ-5D-3L  is a heaThe Beck DI  is a 21-GETE  is a simt-test for continuous variables and Chi-square test for categorical variables. A p-value lower than 0.05 was considered to be significant. Statistical analysis was performed using GraphPad Prism 5 .Data at baseline were expressed as mean ± standard deviation (SD) for continuous variables and in terms of number and percent  for categorical variables. Statistical analysis to assess results obtained after therapy was performed by means a paired Student’s Demographic and clinical data at baseline of our patients are shown in p < 0.0001) and to 24.2 ± 0.6 (24 weeks) (p < 0.0001), ACQ score reduced from 3.48 ± 0.65 (baseline) to 2.32 ± 0.57 (12 weeks) (p = 0.004) and to 1.42 ± 0.92 (24 weeks) (p < 0.0001), EQ-VAS increased from 44.5 ± 7.7 (baseline) to 60.5 ± 6.6 (12 weeks) (p = 0.002) and to 86.7 ± 7.2 (24 weeks) (p < 0.0001) and BECK DI reduced from 14.6 ± 3.68 (baseline) to 9.1 ± 1.64 (12 weeks) (p = 0.002) and to 3.7 ± 1.8 (24 weeks) (p < 0.0001) (ACT score enhanced from 13.5 ± 1.5 (baseline) to 20.3 ± 1.4 (12 weeks) ( 0.0001) .p = 0.003) and to 5.17 ± 0.87 (24 weeks) (p = 0.0002), with a statistically significant increase in all domains over the time (p < 0.05)  to 4.61 ± 0.67 (12 weeks) (the time . The per < 0.05) .No GETE assessment reported poor response or worsening of asthma for any patient at any time point in this study .p < 0.0001) and 0.0 ± 0.0 (p < 0.0001) after 12 and 24 weeks from the first subcutaneous injection of benralizumab, respectively. FeNO levels decreased from 46.79 ± 5.19 (baseline) to 20.68 ± 9.0 (12 weeks) (p < 0.0001) and to 6.69 ± 1.42 (24 weeks) (p < 0.0001) (p = 0.005) and to 3.02 ± 0.20 (24 weeks) (p < 0.0001) (The mean eosinophil blood count decreased from 793.8 ± 301.24 (baseline) to 0.25 ± 0.45 ( 0.0001) . Such st 0.0001) . All theClinical, functional and biological data over study time are summarized in Treatment with benralizumab was safe and well tolerated, with only one patient complaining a self-resolved episode of headache the evening after the first dose injection. After 24 weeks of treatment, only three patients reported mild exacerbations (with a maximum of two in one of them). However, these episodes of exacerbation not required OCS-use and not penalized lung function improvement, resulting from an infectious nature and resolving after appropriate antibiotic therapy.The most relevant aspect of this real-life study regarded asthma control and QoL improvement during an add-on treatment with benralizumab. Severe asthma, especially if poorly controlled, can be very limiting for the normal performance of daily activities due to limited social and physical activity and poor sleep quality with consequent great number of work absences, isolation and reduction in the QoL. In addition, the weight of asthma exacerbations affects the whole family, causing psychological tensions and possible financial problems.In our real-life study all the 10 subjected enrolled experienced with Benralizumab a marked reduction of daily symptoms, nocturnal awakenings and rescue medicine need after 12 weeks of treatment, as documented by the improvement in ACT and ACQ score. The very rapid achievement of daily and nocturnal symptom control experienced by our patients is consistent with a recent analysis of pooled results from the SIROCCO and CALIMA phase III studies . In partSimilarly, we recorded a statistically significant improvement in patient’s perception QoL, as highlighted by the increasing in EQ-VAS, EQ-5D-3L and AQLQ score. Regarding AQLQ, such improvement covered all of the four health domains investigated among which symptoms perception, activity limitation, emotional function and environmental stimuli with a statistically significant improvement after 12 and 24 weeks with respect to baseline.Sandy Khurana et al.  have pre3, and this could have enhanced the beneficial effects of such target treatment. Overall, these results on pulmonary function represent a further objective confirmation for the improvement experienced by patients in terms of asthma control and Qol improvement.The best known characteristic of benralizumab is its reported capacity to induce a fast depletion of eosinophils in blood that has to be related to the unique design and mechanism of action of this monoclonal antibody . InteresIn literature it is also reported an almost complete depletion of eosinophils in sputum and tissues  with benralizumab . UnfortuGlobally treatment with benralizumab appeared safe and well tolerated in our study. After 24 weeks of treatment, three patients reported mild exacerbations (with a maximum of two in one patients), not requiring OCS-use and not penalizing lung function improvement over time. In most cases these were infectious exacerbations, which arose in the winter months and resolved after appropriate antibiotic therapy. Despite the scarce clinical importance of such episodes of exacerbation in our study, it is interesting to remember that Poznanski et al.  in a recThe main strength of our study is to have focused on the benefit of a biological treatment for severe asthma in terms of important clinical aspects, such as symptom control and improvement on quality of life, that are the most perceived results by the patient. Taking into account that the observation period is relatively short, it is possible to hypothesize that the beneficial effects of benralizumab may already be observable after 12 weeks. However, even if this could be considered a strength, it could also be considered as a limitation, since it is not possible to establish whether such benefits persist over longer observation times. Another limitation of our study has to do with the low number of patients enrolled and in the lack of inclusion of all possible comorbidities of the study population (limiting it to rhinosinusitis with polyposis). Anyhow, this limit is in line with the fact that this was the representation of a real-life experience in a dedicated single-center clinic, which makes it more difficult to collect a large number of patients. Furthermore, a placebo effect could not be assessed due to the lack of a placebo control group. Also this limitation can be justified considering that placebo use is unethical in a real-life setting when a proven effective therapy is available. Despite this, it was encouraging to find that also other real-life studies on benralizumab have recorded a similar greater improvement in clinical parameters of their severe asthma patients, also in a shorter follow-up period, compared to the pivotal studies . Some auIn conclusion, our real-life experience supports the effectiveness of benralizumab as an add-on biological treatment in improving nocturnal and diurnal symptom control and mood, as well as restoring patients with severe eosinophilic asthma to an acceptable QoL, as highlighted by the increasing in the ACT, ACQ-6, AQLQ, EQ-VAS, EQ-5D-3L and Beck DI score. It also resulted in an increased lung function and a reduction in eosinophilic inflammation and OCS-use, already only after 12 weeks. These results appear to be in line with those already obtained in the previous randomized controlled trials (RCTs) and real life studies. Benralizumab would represent an optimal choice for improving the clinical treatment and management of patients with severe eosinophilic asthma, especially in those who shows a comorbidity condition of nasal polyps.


Background: We describe the association between longitudinal hemodynamic changes and clinical outcomes in patients with cardiogenic shock (CS) receiving acute mechanical circulatory support devices (AMCS) at a single center. We hypothesized that improved right atrial pressure is associated with better survival in CS.Methods: Retrospective analysis of patients from Tufts Medical Center that received AMCS for CS. Baseline characteristics and invasive hemodynamics were collected, analyzed, and correlated against outcomes. Hemodynamics were recorded at different time intervals during index admission . Logistic regression was performed to determine variables associated with in-hospital mortality.Results: A total of 76 patients had longitudinal hemodynamics available. In hospital mortality occurred in 46% of the cohort. Mean baseline right atrial pressure (RAP) was significantly higher among non-survivors vs. survivors (19.5+6.6 vs. 16.4+5.3 mmHg). Change in right atrial pressure from baseline to before device removal  was significantly different between survivors and non survivors (−6.5 ± 6.9 mmHg vs. −2.5 ± 6.2 mmHg p = 0.03). Unadjusted logistic regression revealed baseline RAP (OR: 1.1 95% CI: 1.0–1.2), 24 h post device implant RAP (OR: 1.3 95% CI: 1.1–1.4), and final RAP (OR: 1.3 95% CI: 1.1–1.5) to be significant predictors of in-hospital mortality. In a multivariate logistic regression baseline RAP was no longer significantly associated with mortality in the overall cohort, while 24 h (OR: 1.26 95% CI: 1.1–1.5) and final RAP (OR: 1.3 95% CI: 1.1–1.6) remained statistically significant.Conclusion: We report a novel retrospective analysis of hemodynamic changes in patients with CS receiving AMCS. Our findings identify the potential importance of venous congestion as a prognostic marker of mortality. Furthermore, early decongestion or reduced RA pressure is associated with better survival in these critically ill CS patients. These observations suggest the need for further study in larger retrospective and prospective cohorts of patients with varying degrees of CS severity. CS is defined by insufficient cardiac output to maintain multi-organ perfusion. The landmark SHould we emergently revascularize Occluded Coronaries for Cardiogenic shocK (SHOCK) trial defined CS associated with acute myocardial infarction (AMI) using clinical and hemodynamic criteria including a systolic blood pressure <90 mmHg or the use of medical therapy to maintain a blood pressure of at least 90 mmHg, evidence of low tissue perfusion, a cardiac index of <2.2 L/min/m 15 mmHg , 4. Syst 15 mmHg . Few stu 15 mmHg . To addr2 and (2) pulmonary capillary wedge pressure ≥ 15 mmHg.Data were retrospectively collected from patients admitted to Tufts Medical Center with refractory CS managed with acute mechanical circulatory support devices from June 2014 to January 2019. Inclusion criteria were patients > 18 years of age who presented with clinical signs of CS requiring a left-sided Impella, Impella 5.0, VA-ECMO, or TandemHeart device for support. Cardiogenic shock was defined using clinical and/or hemodynamic criteria from the SHOCK trial. The clinical criteria were: (1) hypotension: systolic blood pressure <90 mmHg for 30 min before inotropes/vasopressors; (2) end-organ hypoperfusion: cool extremities, oliguria (<30 mL/h) or anuria, altered mental status; and (3) tachycardia >100 beats per minute and/or hemodynamic criteria; (1) cardiac index ≤ 2.2 Lmin/mPatients supported with multiple devices simultaneously or in sequence were included in this study. Exclusion criteria included lack of at least one complete set of available hemodynamic data.Patient characteristics including demographic, laboratory data, hemodynamics, echocardiographic and clinical course were obtained from the medical record. Hemodynamic variables derived from pulmonary artery catheters were collected and analyzed in a retrospective fashion. Hemodynamic variables comprised; right atrial pressure (RA), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI). Moreover, markers of right ventricular dysfunction were calculated from available hemodynamics including RA/PCWP, and pulmonary artery pulsatility index (PAPi). Hemodynamics were recorded at different time intervals during index admission. Pre-specified time points were: (1) Pre-AMCS deployment, or first set of hemodynamics available before AMCS implant, (2) Post AMCS, which included available hemodynamics recorded within 24 h of AMCS implantation, and (3) Final-AMCS, or last available set of hemodynamics before either AMCS explant or death. Lastly, the difference (Δ) between pre-AMCS and final post-AMCS hemodynamics was calculated and correlated against outcomes by logistic regression. For this particular analysis the primary clinical outcome of interest was in hospital all-cause mortality and cohort was stratified based on survivor status independent of the device(s) received.t-tests. A paired student's T-test was used to compare hemodynamics at different time points. Logistic regression was performed to determine variables associated with in-hospital mortality. All variables that were significant in univariate analysis with p < 0.05 were then selected for multivariate analysis. Hosmer-Lemeshow testing was used to show goodness of fit. A p < 0.05 was accepted as statistically significant for all tests. Statistical analysis was performed using GraphPad Prism software  and IBM SPSS Statistics software .Categorical variables are presented as frequencies and percentages and were compared by Fisher's exact test. For continuous variables, results are presented as mean ± standard deviation (SD) and continuous baseline characteristics were compared between survivors and non-survivors using two sample independent n = 35).Hemodynamic data were available for analysis in 76 out of 130 patients receiving AMCS for cardiogenic shock. Baseline characteristics of the study population are shown in p = 0.003). Mean cardiac index was 1.9 + 0.6 L/min/m2 for the total cohort and not significantly different between survivors and non-survivors. Mean PCWP was 24 + 7.5 mmHg and also not significantly different between survivors and non-survivors. Mean pulmonary artery pressure was 31.6 + 9.1 mmHg and was not significantly different between survivors and non-survivors.Hemodynamic and laboratory data are shown in p = 0.03). Compared to baseline values, mean right atrial pressure was lower within 24 h and before device removal among survivors, but was unchanged among non-survivors prior to device removal/death. At both 24 h and before device explant, mean right atrial pressure was lower among survivors compared to non-survivors (p = 0.03). Unadjusted logistic regression revealed baseline RAP (OR 1.1 95% CI: 1.0–1.2), 24 h post device implant RAP (OR: 1.3 95% CI: 1.1–1.4), and final RAP (OR: 1.3 95% CI: 1.1–1.5) to be significant predictors of in-hospital mortality. However, change in RAP from baseline to the last collected was not a significant predictor of in-hospital mortality.Mean baseline right atrial pressure was 17.9 + 6.1 mmHg and was significantly higher among non-survivors  at baseline, 24 h and at the final data recording timepoint was not different among survivors vs. non-survivors.” However, compared to baseline values, the final CI recorded was significantly increased in both survivors and non-survivors although final CI was not a significant predictor of in hospital mortality .In order to observe the association between different RAP values and mortality, we ran multivariate logistic regressions adjusting for other significant predictors of mortality . After adjustment, baseline RAP was no longer significantly associated with mortality in the overall cohort, while 24 h (OR 1.26 95% CI: 1.1–1.5) and final RAP (OR 1.3 95% CI: 1.1–1.6) remained statistically significant.Our central findings are that persistently elevated RA pressure is significantly associated with worse outcomes and that reduced RA pressure within the first 24 h of treatment was an independent predictor of mortality. To our knowledge this is the first study to evaluate temporal changes in hemodynamics and an association with outcomes in patients receiving AMCS for cardiogenic shock. These observations suggest that management algorithms should focus not only in improving systemic blood pressure and cardiac output, but also on early and rapid decongestion. These observations may inform the development of future clinical trials and registries for cardiogenic shock.Recently, the Society for Cardiovascular Angiography and Interventions (SCAI) staging scheme for CS severity identified 5 stages of shock defined by clinical, hemodynamic and metabolic variables. Several recent reports have validated the potential utility of this staging approach –11. AmonThroughout a patient's hospitalization for CS many interventions including fluid resuscitation, mechanical ventilation, hemodialysis, initiation of vasopressors or inotropes and use of AMCS can influence venous congestion. Few reports have examined temporal changes in hemodynamic variables over the course of a patient's hospitalization. We observed that as baseline PCWP was elevated and CI was low before initiating AMCS for CS. Within the first 24 h of initiating AMCS, PCWP or CI were not significantly different between survivors and non-survivors. In contrast, RA pressure was elevated at baseline between survivors and non-survivors, but after initiation of AMCS, survivors showed a statistically significantly lower RA pressure compared to non-survivors. Although baseline RAP was not associated with higher mortality after adjusting for other variables, 24 h RAP and final RAP remained statistically significant. These findings suggest that timely venous decongestion may be an important aspect of CS management that improves survival. Whether specific methods used to reduce venous congestion are superior to others remains largely unexplored. These novel findings also provide important insight into CS by suggesting that venous congestion may worsen outcomes through several mechanisms: (1) causing right heart congestion, thereby leading to a shift in the interventricular septum and reducing LV capacitance and stroke volume; (2) elevated venous congestion contributes to worsening pulmonary congestion by decreasing pulmonary artery compliance; and (3) by causing worsening renal vein congestion, thereby reducing renal perfusion and glomerular filtration, which in turn worsens systemic congestion. With further study the importance of venous decongestion in CS may become a central aspect of patient management.Limitations of the present study include the retrospective nature of the analysis, the small cohort with available clinical data and hemodynamics from admission to discharge which also limited our ability to evaluate the impact of changes in RAP based on etiology of cardiogenic shock (ischemic cardiomyopathy vs. non ischemic cardiomyopathy), SCAI stages, or MCS platform (ECMO vs. Impella vs. IABP). We are planning to replicate this analysis on a larger, multicenter database which will help address those limitations. Furthermore, our analysis included only patients receiving AMCS. This was intentional to identify critically ill shock patients. Other important hemodynamic parameters associated with outcomes in CS were not included in this analysis, like Cardiac Power Output (CPO). However, future studies will need to study temporal changes in hemodynamics across all stages of CS severity. Also, the inherent selection bias regarding device appropriation per patient. Finally, the small size of the study did not allow for a rigorous multivariate analysis.In conclusion, we report a novel retrospective analysis of hemodynamic changes in patients with CS receiving AMCS. Our findings identify the potential importance of venous congestion as a prognostic marker of mortality and further that early decongestion or reduced RA pressure is associated with better survival in these critically ill CS patients. These observations suggest the need for further study in larger retrospective and prospective cohorts of patients with varying degrees of CS severity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.All authors contributed to the design and implementation of the research, to the analysis of the results, and to the writing of the manuscript.NK has received research funding from Abbott; Abiomed Inc., Boston Scientific Inc.,Getinge; LivaNova; MD Start Inc., and preCARDIA Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To the Editor,We thank Dr Yu for his comments in response to our article. According to Dr Yu, we did not sufficiently address 2 misconceptions on perioperative management in patients with a pheochromocytoma. He states that we suggested that control of hypertension is more important than prevention of cardiovascular complications, based on the order in which we mentioned these goals. These goals, however, were described in random order and we did not mean to imply that one was more important than the other. Fluctuations in blood pressure and heart rate are nevertheless common in pheochromocytoma, may have deleterious effects per se, and are amenable to medical management. We do agree with Dr Yu that normotension does not preclude the occurrence of cardiovascular complications, an important message to which we have also brought attention.In response to the alleged second misconception in our paper, Dr Yu suggests that the perioperative management should be more individualized. We agree that in general, any treatment should be tailored to the patient. In fact, when aiming at predefined perioperative hemodynamic targets as we suggest, this automatically translates into an individualized approach to the selection of drugs and doses. Unfortunately, however, it is still largely unknown which specific preoperative factors reliably predict a person’s perioperative risk and the ensuing optimal treatment. His statement that preoperative echocardiography and 24-hour ambulatory blood pressure monitoring is unnecessary in patients harboring a small pheochromocytoma  who are physically fit implies that pheochromocytoma/paraganglioma (PPGL)-related cardiovascular complications are negligible under these circumstances. The notion of skipping these routine and noninvasive investigations is, however, not corroborated by the literature that was cited. For example, the study by Yu et al demonstrated that 17% of patients with a tumor smaller than 3 cm also developed severe cardiovascular complications during unrelated procedures . FurtherIn conclusion, a small PPGL size or the absence of symptoms does not reliably predict a low perioperative risk. We do agree that the controversy with respect to the clinical value of presurgical treatment with α-adrenoreceptor blockers in modern-day medicine could be resolved only by a well-designed placebo-controlled trial. Until then, we recommend following the Endocrine Society’s guideline that all patients with a PPGL, regardless of blood pressure and tumor size, should undergo preoperative evaluation of cardiac function and blood pressure and receive presurgical treatment with α-adrenoreceptor blockers .


Cond), is rarely used in children. PVR can also be obtained by 3D-echocardiography volume data combined with simultaneously measured pressure data by a mini pressure-wire (PVR3DE). We sought to investigate the feasibility of both methods in patients with univentricular hearts and to compare them, including hemodynamic changes.The gold standard to obtain pressure-volume relations (PVR) of the heart, the conductance technology (PVR3DE and PVRCond were assessed under baseline conditions and stimulation with dobutamine.We studied 19 patients (age 2–29 years). PVR3DE was successful in all patients. Obtaining PVRCond was possible in 15 patients during baseline (79%) and in 12 patients under dobutamine (63%). Both methods showed that end-systolic elastance (Ees) and arterial elastance (Ea) increased under dobutamine and that Tau showed a statistically significant decrease. Intraclass correlation  showed moderate to good agreement between methods: Ees: 0.873 (0.711–0.945), Ea: 0.709 (0.336–0.873), Tau: 0.867 (0.697–0.942). Bland-Altman analyses showed an acceptable bias with wider limits of agreement: Ees: 1.63 mmHg/ml (-3.83–7.08 mmHg/ml), Ea: 0.53 mmHg/ml (-5.23–6.28 mmHg/ml), Tau: -0,76 ms (-10.73–9.21 ms).Obtaining PVR3DE in a single ventricle was easier, faster and more successful than PVRCond. PVR3DE provides a promising and needed alternative to the conductance technology for the assessment of cardiac function in univentricular hearts.Changes of PVR-specific parameters under dobutamine stimulation were reflected in the same way by both methods. However, the absolute values for these parameters could vary between methods and, therefore, methods are not interchangeable. Obtaining PVR Congenital heart defects (CHD) occur with a prevalence of 107: 10,000 live births of which 29.4% are severe defects requiring early intervention  3D volumes/s; corresponding to 16.7 ± 5.1 [30 – 10] 3D volumes per cardiac cycle respectively. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were calculated using TomTec 4D LV-Analysis software 3.1 . The apex and the Av-valve were marked. First, the automated border detection traced the contours of the ventricle. Second, manual adjustments to these traced contours were made as needed. A volume-time-curve was then computed by the software .Continuous monitoring of cardiovascular pressures was performed using a 0.014 French (0.036 mm) mini pressure-wire . This high-fidelity guidance wire carries a micromanometer at its tip and is attached to an external working station , allowing instantaneous online recording of pressure–time curves. Pressure data were measured with the Radi Analyzer  with a sampling rate of 200 Hz. This mini pressure-wire was calibrated and advanced into the ventricle. In general, a microcatheter is suitable for this. Because our study was performed during a routine and clinically indicated cardiac catheterization we used the 3F or 4F sheath and a 3F or 4F pigtail or multi-purpose catheter that was needed for the examination, anyway. In patients with Fontan-circulation an arterial access was necessary. In patients with Glenn-circulation we used a venous access, if possible. If correct insertion of the catheter was not possible an arterial access was used. Continuous monitoring of pressure–time curves allowed assessment of the position of the mini pressure-wire inside the guiding catheter without additional radiation until the pressure-wire was placed properly in the ventricle. To confirm the proper position of the wire within the ventricle in this study, short radiation was used.3DE, full volume 3D datasets and pressure measurements were acquired simultaneously.For obtainment of PVR3DE were obtained by the same customized software by combination of the synchronized volume-time curves derived by 3DE and the simultaneously acquired pressure-time curves . For insertion of this catheter a 5F sheath is necessary. Before insertion, the catheter was placed into 0.9% saline solution and the pressure sensor was calibrated. Insertion of the catheter into the ventricle was done using fluoroscopic guidance. Signals were displayed by the CFL-M Inca . Volume calibration was done in baseline measurements using end diastolic volume (EDV) and end systolic volume (ESV) obtained by 3DE as references [For obtainment of PVRferences , 13.3DE and PVRCond, systolic function was measured using end-systolic elastance (Ees), which was calculated by single-beat estimation method [From the PVRn method . The effn method . For then method .The early active relaxation process (decay of the ventricular pressure during isovolumetric relaxation) is reflected by the isovolumetric relaxation constant Tau. Tau was calculated using a logistic fit , 18. Max3DE were done under baseline conditions (BL). Then the mini pressure-wire was removed and the conductance catheter was inserted into the ventricle for baseline measurements of PVRCond. If possible, catheterization of the ventricle was done via a venous access in patiens with a Glenn-circulation. Otherwise an arterial access via the aorta was used. The conductance catheter was left in place and 10 μg/kg/min of dobutamine were administered for 10 minutes until a steady state of heart rate and blood pressure was reached (Dobu). Then measurement of PVRCond under dobutamine stimulation was performed. The conductance catheter was removed and the mini pressure-wire was inserted. PVR3DE under dobutamine stimulation was assessed. This was done because we observed in previous studies echocardiographic artifacts produced by the conductance catheter, which impaired the semiautomatic contour analysis during 3DE volume calculation. Also, the mini pressure-wire disturbed conductance measurements [First, measurements of PVRurements .Statistical analyses were performed using Graph Pad Prism 5  and IBM PSS Version 25 .The differences between BL and stimulation with dobutamin were analyzed using paired Student t-tests or Wilcoxon signed-rank tests, as appropriate. Data for Tau, Ees, Ea and EDV10 were log transformed before analysis. Differences were considered to be significant when the p-value <0.05.Comparison between Tau, Ees, Ea and EDV10 derived from PVR3DE and PVRCond were performed using Bland–Altman analysis and Intraclass correlation (ICC) with one-way random effects.Data are presented as mean ± standard deviation or median and range.We included 19 patients aged 2–29 years in the study. Twelve patients had a single right ventricle and 7 patients a left ventricle.3DE in all patients under baseline as well as dobutamine condition. We decided to use the same software for all measurements and choose the software designed for a left ventricle because the single ventricles in our study are systemic ventricles. Moreover, we found that this software allows for the most individual adjustment needed for the individual geometry of single ventricles. In one patient 3DE-data sets under dobutamine could not be analyzed due to a technical defect during acquisition resulting in an insufficient frame rate. The procedure to assess PVR3DE took 5–10 minutes for each condition.We were able to acquire PVRCond were not possible in all patients. Placement and measurement took 10 to 30 minutes. In four patients (21%) we were not able to place the conductance catheter correctly so that an adequate measurement was not possible. In another three patients (15.7%) an adequate positioning of the catheter was only given under baseline conditions but not under dobutamine stimulation. One patient had to be excluded due to arrhythmia, although measurements were technically possible.Acquisitions of PVR3DE and PVRCond in 14 patients  for Ees, -0.76 ms (-10.73–9.21 ms) for Tau, 0.53 mmHg/ml (-5.23–6.28 mmHg/ml) for Ea and 5.74 ml (-27.25–38.73 ml) for EDV10 .ICC and their 95% confidence interval was 0.873 (0.711–0.945) for Ees, 0.867 (0.697–0.942) for Tau, 0.709 (0.336–0.873) for Ea and 0.916 (0.8–0.965) for EDV10.In this study, we assessed PVR in univentricular hearts with two different methods: Volume data from 3DE combined with pressure data from a mini pressure-wire and the conductance technology. We compared these two methods in regard to feasibility and parameters obtained from PVR under hemodynamic changes.3DE was possible in all patients while the measurement with Cond was less successful, mostly due to the difficulty of placing the relatively stiff catheter in a correct position in anatomically atypically formed ventricles. In some patients, the adequately positioned conductance catheter under baseline conditions came into an inadequate position under administration of dobutamine. This observation of about 21% unsuccessful placement and/or insufficient signal quality is in accordance with previously reported data of a conductance catheter study in univentricular hearts [3DE, PVRCond was associated with a longer examination time and more radiation that was needed for the placement of the catheter.We could show that obtaining PVR3DE was good with an interobserver coefficient of variation below 10% [In previous studies we could show that reproducibility of PVRelow 10% .We found that Ees as a parameter for systolic function and contractility and Ea as a measure of systemic afterload showed a statistically significant increase under stimulation with dobutamine. Our values for Ees and Ea measured by Cond are comparable to those of Schlangen et al. in their conductance catheter study in univentricular hearts , 19. We th confidence interval showed good to moderate agreement [Comparing Ees, Tau, Ea and EDV10 we found that both methods reflected changes between baseline and stimulation with dobutamine in the same way. When comparing the absolute values for these parameters, ICC and its 95greement . The Blagreement . For the3DE and PVRCond in small healthy biventricular porcine hearts we found a better agreement between methods [In our previous study in which we compared PVR methods . One rea methods , 25. The3DE and PVRCond could not be obtained simultaneously. Therefore, slight hemodynamic changes e.g. non-identical pressures between 3DE and Cond measurements are possible.For technical reasons as explained above, PVRTo achieve satisfactory temporal and spatial resolution especially in infant hearts, 3D full- volume datasets are needed. They are recorded over 4 cardiac cycles. In consequence, beat-to-beat variability cannot be assessed. The existing technique of single-beat acquisition of 3D datasets does not provide adequate temporal and spatial resolution for the calculation of beat-to-beat variability in the pediatric heart . The curWe calibrated the conductance derived baseline volumes with volumes derived by 3DE. Our ethical committee did not allow for additional measurements by thermodiluation or cardiac magnetic resonance. We cannot rule out that this might have led to bias. Basing the calibration of baseline volumetric data on the same reference in the beginning enabled us to study the tracking of hemodynamic changes of the two methods without an additional bias of a third volumetric method.For assessment of load-independent variables, we desired a preload-reduction by an inflated balloon-catheter in the vena cava inferior or Fontan-tunnel. Unfortunately, our ethical committee rejected the request for this additional procedure.Another limitation is the relatively small sample size of this study due to the invasive procedureAssessment of systolic and diastolic ventricular function in patients with univentricular hearts is needed and can help with decisions on pharmacological treatment. 3DE is available in most centers for pediatric cardiology and the placement of the pressure-wire without radiation can even take place outside of a catheter laboratory. In general, the pressure-wire can be left in place for a while (under heparinization) to perform testing like volume load or the effect of drugs like inotropic agents or vasodilators.3DE and PVRCond. However, the absolute values for these parameters could vary between methods and, therefore, methods are not interchangeable. Obtaining PVR3DE in a single ventricle was more feasible, faster and less invasive regarding size of sheath and radiation than obtaining PVRCond. Consequently, PVR obtained by 3DE and mini pressure-wire provide a promising and needed alternative to the conductance technology for the assessment of cardiac function in univentricular hearts.We found that hemodynamic changes between baseline and stimulation with dobutamine were reflected in the same way by PVR-specific parameters measured by both, PVRS1 Fig3DE = 3D echocardiography, Cond = conductance technology, Ees = end-systolic elastance, Ea = effective arterial elastance, EDV10 = EDV at an EDP of 10.0 mmHg, dotted lines = bias and limits of agreement.(TIF)Click here for additional data file.S2 FigPoints = baseline 3DE; circles = Dobu 3DE; filled squares = baseline Cond; open squares = Dobu Cond.(TIF)Click here for additional data file.