Percutaneous kidney biopsies are important tools for the diagnosis of kidney diseases. Nephrologists must be familiar with the expected complications of the procedure to provide an adequate informed consent. Here, we present a quality improvement analysis that reviews the complication rate of percutaneous kidney biopsies performed over a 2-year period by nephrologists at a single center, and that tabulates the nature and timing of these events.From a single center cohort, pre- and post-biopsy anthropomorphic and clinical measurements were collected. Post-biopsy complications were tracked and sorted into either major or minor complications. Statistical tests were used to analyze complication incidence across the pre- and post-biopsy measurements obtained.Of the 154 nephrologist-performed percutaneous native kidney biopsies, 2 biopsies (1.3%) were found to result in a major complication. Both major complications were detected within 4 hours of the biopsy. Analysis of the pre-biopsy and post-biopsy measurements found that the proportion of complications was higher in patients with hematuria prior to biopsy. It was also found that patients with complications were statistically younger and had fewer comorbidities. Under univariable analysis, older age was associated with a lower incidence rate ratio for complications. However, no pre-or-post biopsy measurement or characteristic had a statistically significant change in incidence rate ratio under multivariable analysis.Percutaneous kidney biopsies were found to be low risk when performed by nephrologists in this single center cohort. Consistent with past literature, life threatening major complications rarely occurred and were reliably identified within 4 hours of biopsy, suggesting that centers can consider reduced observation times without compromising patient safety. Minor complications, such as pain, were more likely to occur in younger, healthier patients, and in those with hematuria prior to biopsy. This extensive tabulation of all biopsy adverse events is the first of its kind and will be beneficial for nephrologists to inform discussions with patients about expectations and risk-benefit of this procedure. Percutaneous kidney biopsies are considered the gold standard for diagnosis and management of kidney diseases . They haThe significant vascularity and the large amount of cardiac output the kidney receives relative to its size, lends the procedure to bleeding complications. Several large retrospective and prospective studies exploring biopsy complications have shown that bleeding related complications are most common and can be quite frequent 50–90%) , 3–6. Ho0% , 3–6.The aim of this quality improvement analysis was to contribute to the existing data on the safety of percutaneous kidney biopsy with a specific focus on nephrologists performing the procedure for nephrology specific indications. It was anticipated that our findings would match existing data for biopsy safety and be able to provide reassurance that biopsies performed by trained nephrologists are low risk. The standard post-procedure observation period at our center was also assessed to determine if it could be safely decreased.A retrospective chart review was performed on patients who received an outpatient referral for native kidney biopsy at the University of Wisconsin Hospitals and Clinics between January 2016 and January 2018. Any biopsy done outside the nephrology division was excluded from the study. Per typical protocol, patients were asked to hold antiplatelet therapy and anticoagulants for 2–5 days prior to the biopsy  and 5 days for aspirin, clopidogrel and warfarin). The patients were admitted to the hospital prior to the biopsy and had baseline blood work drawn . The procedure occurred in the radiology suite with an ultrasound technologist guiding a nephrologist using an 18-gauge side cutting percutaneous biopsy device for the majority of procedures. There were a few procedures done with 14- and 16-gauge end cutting needles, but this frequency was not tracked. A nephrology attending physician was present for each biopsy where a nephrology fellow was the primary operator. After the procedure, the patient was returned to their inpatient room for observation. Nursing staff were instructed to measure vital signs every 15 minutes for 1 hour then every 30 minutes for 1 hour and then every 4 hours thereafter. Pain was assessed at each vital sign observation using the visual analogue scale. Blood work was drawn at 4 hours and again in the morning. If the hematocrit levels were stable, the patient was discharged home with instructions to return to the hospital for any significant increase in pain, lightheadedness, dizziness or other change in condition. If the hematocrit fell by more than 3 points at either check, a non-contrast CT scan was ordered to assess for bleeding.Two medical student research assistants defined study variables in consultation with the study principal investigators and developed a password-protected electronic abstraction form in Microsoft Office Excel. A codebook was developed for each categorical variable with comprehensive, mutually exclusive numerical codes to ensure accuracy and consistency. Variables included major complications  and minor complications , hypertension (> 180/110 mmHg), and hypotension (< 90/60 mmHg)).Patients were randomly assigned to a research assistant’s panel for data abstraction. The frequency, timing, and nature of kidney biopsy related complications was recorded. Patient identifying factors were eliminated in accordance with quality improvement principles. Pre and post biopsy characteristics were analyzed for predictive potential for complications. The first 10 patients in each research assistant’s data set were assigned twice and re-coded to ensure inter-rater and intra-rater reliability. No coding discrepancies were identified.p-values < 0.05 were considered statistically significant. All analyses were conducted using STATA version 15 SE .To determine if any patient characteristics were associated with kidney biopsy complications, we performed the following analyses. Baseline characteristics and patient demographic information were summarized using proportions and Fisher’s exact tests. Continuous variables such as age, BMI and Charlson score were expressed as mean plus standard deviation and analyzed using t-tests. We modelled the incidence of complications using Kaplan Meier Incidence curves and a Poisson regression. Both a univariable and a multivariable Poisson model were conducted with variables deemed risk factors for complications. Our multivariable model was conducted using all variables included in the univariable model, with exclusions only made in cases of redundancy. Missing data points were handled by deletion/omission from modelling in listwise fashion. All 2. Patient comorbidity was estimated with the Charlson Comorbidity Index, of which a higher index predicts a lower 10-year survival. The average Charlson Comorbidity Index of our cohort was 3.69, which estimates a 62% 10-year survival. The diagnoses resulting from biopsy are also shown. All 154 biopsies resulted in sufficient tissue for pathology reading. Under the category of “Others,” we included low volume diagnoses (occurring less than three time) such as amyloidosis, HIV nephropathy, light chain tubulopathy, pyelonephritis, radiation induced kidney injury, thin basement membrane disease, thrombotic microangiopathy and microangiopathy likely due to bone marrow transplant. While interesting to note, these did not result in large enough numbers to be associated with any biopsy complication therefore were not listed individually. Pathology readings of non-specific renal changes occurred 9 times and were classified as “other” due to not being a renal disease diagnosis.Of the 178 patients sent for percutaneous biopsy, 154 were included in the study  resulted in a major complication Table . One bioThe remaining complications were considered minor complications. The most common minor complication reported was pain; reported in 53 biopsies. The average subjective rating on the pain visual analogue scale was 3.1/10 at rest and 4.0/10 with activity. The next most common minor complication was a decrease in hematocrit, occurring in 30 biopsies. A drop of 3 or more points in hematocrit was followed with abdominal CT scan 29 times to search for hemorrhage, which occurred once. All other CT scans or ultrasounds revealed small hematomas, occurring 13 times, or showed expected post kidney biopsy changes such as trace peri-nephric blood.The total number of minor complications documented 106. Most complications, 54(50%), were reported within 4 hours after biopsy, followed by 38 35.2%) complications reported within 4–8 hours post biopsy, followed by 7 (6.5%) reported within 8–12 hours post biopsy, and the remaining 9 (8.3%) of complications reported 12 hours post biopsy. (Table % complicTable Among age it was found that the average age of patients who underwent biopsies that resulted in minor complications was significantly lower than those who did not have complications Table . Similarn = 2) limited statistical analysis that could be performed for this group.The small number of major complications (This quality improvement study analyzed t 154 patients who underwent native percutaneous kidney biopsies performed by a nephrologist, to determine complication rate at our center, and to determine patient characteristics associated with kidney biopsy complications . There was a major complication rate of 1.3%, which is in line with the reported range of < 1–9% . For comIn our population, minor complications were found in 47% of biopsies. All these complications resolved with minimal to no intervention within 24 hours of the procedure. Table It was noted that minor bleeding complications resulting in a hematoma were reported in only 13 biopsies or 8.4%. This contrasts with many reported values ranging from 57 to 91% [Although none of the collected data stood out in multivariate analysis, it was interesting to note that younger patients and those with lower Charlson comorbidity indices were more likely to report minor complications. Younger age has been reported in the literature as a risk factor for kidney biopsy complications , 18 but Although the literature has shown there to be an increased bleeding risk associated with diagnoses such as acute tubular necrosis, autoimmune conditions, and hypertensive kidney disease, no associations have been substantiated consistently . Given tPeriods of observation after a kidney biopsy have come into question. Although collection methods differ, past literature supports that 85–91.6% of complications occurred 12 hours or less from the time of the biopsy . Indeed,Studies have also suggested that the risk of complications in kidney biopsies is reduced when the performer has done greater than 4 biopsies per year . While tOur study provides information on the low rate of major complications in a single center where nephrologists perform the kidney biopsies for nephrology indications. In addition to this contemporary update, we provide information on the minor complications to inform nephrologists’ discussions about what patients can expect. In addition, we provide evidence that supports prior reports that complications most often exist in the 4–5 hours post biopsy, therefore observation periods can reflect this practice safely. There were limitations in our study given its single center, observational nature and relatively small sample size as this restricted the number of major complications and limited the statistical analysis that could be performed. Additionally, we did not track the type of biopsy device that was used, nor the number of passes taken. These factors have been shown to influence the complication rate . FinallyOur study was successful in providing further evidence to support the safety of percutaneous kidney biopsies, with major complication rates comparable to the rates in existing literature. The strengths of our study, however, were found in the extensive tabulation of events. Through the tabulation of timing, we were able to show that shorter observation periods could limit hospital stays without compromising patient safety. Through the tabulation of post-biopsy complications, we added to the existing knowledge of post-biopsy expectations. These tabulations also allowed the statistical analysis which showed minor complications to be more frequent in younger, healthier patients. Despite the limitations of being a small, retrospective, single center study, we believe our study is a good starting point towards obtaining aclearer picture of the incidence of events such as pain and nausea, that will allow nephrologists tomore confidently and adequately educate their patients about what to expect when undergoing a kidney biopsy. To expand on our findings, future studies can examine the effect of different gauge needles, the number of passes in a biopsy, and the experience of the biopsy performer on the post-biopsy complication rate.


Blood pressure (BP) refers to the pressure that the blood exerts on the walls of blood vessels. There is a number of evidences that show that depression, anxiety, and also stress have a high incidence in people suffering from hypertension.To correlate blood pressure levels with psychopathological symptomatology levels and to compare differences between genders, age and education levels.This was a descriptive, inferential and correlational study encompassing 1407 participants, aged from 18 – 89 years of age (average age = 36 years). Measures included biomedical data - systolic blood pressure and diastolic blood pressure, arrhythmias and heartbeat, as well as the demographic variables - sex, age and education of the participants; mental health  was measured using the Portuguese version of the BSI.In the present study there were no statistically significant relationships between Systolic Blood Pressure, Diastolic Blood Pressure and General Symptom Index, as well as for each BSI dimension. Nevertheless, statistically significant differences were found between Diastolic Blood Pressure and obsessions-compulsions, interpersonal sensibility and hostility. Also, there are statistically significant differences for BP according to gender and education.This study brings important contributions to the study of the associations between blood pressure and mental health, with import implications for intervention and prevention.


Although kidney transplantation significantly improves the quality of life of patients with end-stage renal disease (ESRD), the prevalence of cardiovascular disease (CVD) in kidney transplant recipients (KTRs) remains high. Atherosclerosis, post-transplantation metabolic changes, immunosuppressive therapy, and periodontitis contribute to elevated cardiovascular risk in this population. The aim of the study was to evaluate carotid intima-media thickness (IMT) as a surrogate marker of atherosclerosis and to analyze the possible risk factors for IMT in Dalmatian KTRs. Ninety-three KTRs were included in this study. Data on clinical and laboratory parameters, body composition, anthropometry, advanced glycation end-product (AGE) measurements, blood pressure, and arterial stiffness were collected. All participants underwent ultrasound examination of IMT and evaluation of periodontal status. KTRs with carotid IMT ≥ 0.9 were significantly older, had a lower level of total cholesterol, fat mass, end-diastolic velocity (EDV), and had fewer teeth. They also had significantly higher values of pulse wave velocity (PWV) and resistive index (RI). We found positive correlations between carotid IMT and duration of dialysis, age, PWV, AGE, RI, and average total clinical attachment level (CAL). The regression model showed that IMT in KTRs is associated with higher PWV, lower fat mass, and fewer teeth. The results of our study suggest that nutritional and periodontal status are associated with carotid IMT in KTRs. Chronic kidney disease (CKD) and especially end-stage renal disease (ESRD) are known as great risk factors for cardiovascular (CV) events and complications . Kidney Atherosclerosis is believed to be one of the major contributors to elevated CV risk in the CKD population ,6. MechaThe sonographically measured intima-media thickness (IMT) is considered to represent a surrogate marker for atherosclerosis. The IMT measurement can be applied in clinical practice to detect early atherosclerosis and predict atherosclerotic plaque instability in a variety of populations . Higher The impact of KTR on carotid IMT is conflicting. One study demonstrated carotid IMT to progressively increase early  after kidney transplantation , while, The role of nutrition and nutritional status in the pathogenesis of atherosclerosis and CV risk is receiving more and more attention in the general population  and in KPeriodontitis is one of the most common chronic oral diseases in the adult population that affects supportive tooth tissues, causing their reduction and finally can lead to tooth loss . Severe AGEs are stable compounds that accumulate on long-lived proteins. AGEs are formed by the reaction of proteins or lipids with aldose sugars and further molecular rearrangements. Age, the status of oxidative stress, inflammation, liver and kidney function, nutrition, and diet also influence AGE accumulation .In CKD, accumulation of AGEs is attributed to impaired renal clearance, increased endogenous formation, and excess dietary intake ,26. AlthThe aim of the study was to evaluate carotid intima-media thickness (IMT) as a surrogate marker of atherosclerosis and also to analyze possible risk factors for carotid IMT in Dalmatian KTRs.n = 93) older than 18 years of age, with functioning kidneys and no mobility difficulties, were included in this cross-sectional study conducted at the outpatient clinic of the Department of Nephrology and Dialysis, University Hospital of Split, Croatia, between July 2019 and October 2019. The study protocol was approved by the Ethics Committee of the University Hospital of Split, Croatia.Kidney transplant recipients , type, and duration of dialysis treatment before KTX were obtained.2). A complete blood count was obtained using a hematology analyzer .Regarding laboratory parameters, all study participants underwent usual peripheral blood sampling, and they were asked to obtain a 24 h urine sample on the same day as the body composition and blood pressure measurement. We collected data on levels of urea (mmol/L), creatinine (mmol/L), uric acid (mmol/L), serum albumin (g/L), phosphates (mmol/L), C-reactive protein , calcium (mmol/L), glucose (mmol/L), triglycerides (mmol/L), total cholesterol (mmol/L), low-density lipoprotein cholesterol (LDL) (mmol/L), hemoglobin (g/L), mean cellular volume (MCV), sodium (mmol/L), potassium (mmol/L), and eGFR using CKD-EPI  who were blinded to the clinical data and periodontal status of the patient. Ultrasound evaluation of the carotid artery was performed in the B-mode technique using a high-resolution ultrasound scanner  equipped with a 7–10 MHz linear transducer. The patient was examined in the supine position with the neck semiextended. After optimization of image quality, the scanning was started from the proximal part of the common carotid artery toward the bifurcation, followed by scanning the internal carotid artery. Dynamic images were stored for the evaluation of intima-media thickness (IMT), which was defined as the distance between the leading edges of the lumen interface and the media–adventitia interface at the far wall.The points of measurement were 0.5 cm, 1 cm, and 2 cm distances from the bifurcation in the plaque-free area. The final carotid IMT was calculated as the mean of these six measurements (three on both sides). The increased value was defined as IMT ≥ 0.9 mm. The atheromatous plaque was considered as a focal wall thickening of at least 50% greater than that of the surrounding vessel wall.The evaluation of quantitative ultrasound Doppler parameters included peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) of both internal carotid arteries.Body composition was assessed by bioelectrical impedance analysis (BIA) using an MC-780 Multi Frequency Segmental Body Analyzer  for each participant. Data on muscle mass (kg), skeletal muscle mass (kg), skeletal muscle mass percentage (%), body mass (kg), fat mass (kg), fat mass percentage (%), fat-free mass (kg), and visceral fat were obtained. All participants were asked not to eat or drink excessively, exercise, or consume alcohol at least one day before the measurement. They also did not take any food or liquid for a minimum period of three hours prior to the measurement.When it comes to anthropometric parameters, data on height, weight, body mass index (BMI), waist circumference (WC), mid-upper arm circumference (MUAC), and waist-to-height ratio (WHtR) were obtained for each study subject.AGEs were measured from the skin by skin autofluorescence (SAF) using a noninvasive desktop device . SAF is expressed in arbitrary units (AU) . The devThe Agedio B 900  device, which uses oscillometry technology, was used to assess central and peripheral blood pressure and arterial stiffness. Data on pulse wave velocity (PWV) (m/s), augmentation index (AiX) (%), peripheral systolic blood pressure (pSBP), peripheral diastolic blood pressure (pDBP), peripheral mean arterial pressure (pMAP), peripheral pulse pressure (pPP), central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), central mean arterial pressure (cMAP), and central pulse pressure (cPP) were obtained. After measuring the upper arm circumference, the right-sized cuff was selected and positioned according to the user manual. All measurements were performed with every participant sitting comfortably with their back and arm supported, feet flat on the ground, and legs not crossed. Participants were advised not to speak or move during the measurement.The structured periodontal anamnesis based on the questionnaire was taken from all participants. The frequency of dental check-ups, personal and family history of periodontitis, smoking and oral hygiene habits, and clinical symptoms of periodontitis were recorded. A comprehensive periodontal examination was performed by an experienced periodontist (MR) using the UNC 15 mm periodontal probe . All clinical parameters measured on six sites were recorded: the full-mouth plaque score (FMPS), bleeding on probing (BOP), probing pocket depth (PPD), gingival recession (GR), and clinical attachment level (CAL). FMPS and BOP were expressed in percentages, whereas PPD, GR, and CAL were expressed in millimeters. The number of teeth, mean PD, mean CAL, BOP, FMPS, number of teeth with PD of 4, 5, and ≥6 mm, percent of sites with PD of 4, 5, and ≥6 mm, and number of teeth with interdental CAL of 1–2, 3–4, and ≥5 mm were periodontal variables assessed for each participant and included in the analysis.Periodontal variables were considered in order to determine periodontal stages according to the new classification scheme, as proposed by Tonetti et al. . Mild top < 0.05. The entire statistical analysis was performed using the free software environment for statistical computing, R version 4.0.0 [The normality of the data was assessed with the Shapiro–Wilk test. In cases of parametric distribution, numerical data were described with means and standard deviations (SDs), and with medians and interquartile ranges (IQRs) in cases of nonparametric distribution. Categorical data were described with numbers and percentages. To assess if there were any statistical differences between the groups of KTRs with increased IMT  and those without , the chi-square test was used for categorical data, T-test for parametric numerical data, and the Mann–Whitney U test for nonparametric numerical data. Spearman’s rank correlation was used to assess if there were any statistically significant correlation between IMT and measured numerical parameters. Finally, multivariate logistic regression analysis was performed to find predictors for atherosclerosis in KTRs, where all statistically significant variables identified from descriptive statistics and correlation analysis (with added gender information) were used as independent variables (named Full model). All these variables were then used as input for the Boruta algorithm  as a feaon 4.0.0 .This study included 93 KTR patients. The exclusion criteria and number of excluded patients are presented in Correlations between IMT and measured parameters are shown in p-value > 0.05).Results of multivariate logistic regression models aiming to find predictors for atherosclerosis in KTRs are shown in The final regression model showed that the greater odds of developing atherosclerosis in KTRs are associated with higher levels of PWV, lower fat mass, and fewer teeth. Average total CAL and total cholesterol levels were also selected to remain in the final model. However, these variables were not statistically significant . The totTo our knowledge, this is the first study that evaluated the associations of carotid IMT with AGEs, body mass composition, periodontal, and blood pressure parameters in KTRs.The results of our study state that 27% of KTRs have IMT ≥ 0.9 mm and that those KTRs with IMT ≥ 0.9 mm were statistically older. It is well known that age is a major risk factor for atherosclerotic cardiovascular disease . AdditioTherefore, we found a significant positive correlation between dialysis duration before KTR and IMT among all study subjects. In contrast to our study, no relationship between IMT and duration of dialysis treatment was found in a previous study in hemodialysis patients . The posAmong the 112 KTRs with ultrasound and periodontal status examined in our study, 93 (83.08%) of them had periodontists. These results suggest a high prevalence of periodontitis in this population of patients, even higher than in patients with stage 5 CKD . MoreoveAdditionally, KTRs with IMT ≥ 0.9 mm had statistically higher levels of oscillometric determined PWV as an indirect parameter of arterial stiffness . In addiInterestingly, we found no statistically significant differences between KTRs regarding carotid IMT thickness in parameters of central or peripheral blood pressure. Some studies suggest higher levels of blood pressure in people with higher levels of arterial stiffness in KTRs ,47, and It is well known that carotid IMT is a surrogate marker for the presence and progression of atherosclerosis . Our resAdditionally, our results showed a significant positive correlation between AGEs and carotid IMT among all study subjects. AGEs are involved in the progression of atherosclerosis and some chronic diseases, such as chronic renal failure, Alzheimer’s disease, and diabetes mellitus ,53,54,55The results showed a significant negative correlation between phase angle and carotid IMT. Phase angle is a bioimpedance analysis parameter that indirectly shows body cell mass and is associated with muscle mass, strength, physical performance, quality-of-life scale, and hospitalization-free survival in maintenance HD patients . Additio2 [2. To clarify this association between fat mass and atherosclerosis risk in KTRs, future studies with a larger number of KTRs are needed in the prospective study design.On the other hand, our final regression model showed that one of the greater odds for the higher value of carotid IMT in this population of KTRs is lower fat mass. This finding is in contrast with a previous study conducted by Mohsen et al., who evaluated atherosclerotic changes in the carotid artery following KTR and found that IMT measures significantly correlated with age and BMI . A possi2 .Our popuAnother important factor is vitamin D, a relevant element for CV risk and nutritional status in KTRs , which wOur study has some limitations, which primarily come from the cross-sectional design, which, as such, prevents us from any causal conclusions. Possible limitations to the measurement of AGEs in our study may include endogenous factors present in the skin that absorb emission light, such as melanin in dark-skinned subjects, acute illness, and strenuous exercise associated with glycoxidative stress, exogenous factors such as diet, and, for example, the use of skincare products. Considering the limitations, measurement with the AGE reader is a validated method with 5% to 6% intraobserver variation in repeated autofluorescence measurements within a day . ProspecThe results from this study suggest possible associations between AGEs and nutritional and periodontal status with carotid IMT as a surrogate marker of atherosclerosis in KTRs. Nutritional intervention for those patients who have lost teeth is a great challenge. It should include individualized dental and nutritional counseling. Therefore, consumption of soft foods should be advised, and if that nutritional intervention does not meet the needs, oral nutritional supplementation should be implemented. All in all, more attention should be paid to the nutritional and dental management of those KTRs with tooth loss.


Cardiorenal syndrome encompasses complex multifactorial facets and carries significant morbidity and mortality worldwide. The bi-directional relationship between the heart and kidneys, where dysfunction in one organ worsens the function of the other, has been the leading motor for research in the last few years. In the pathophysiological process, small noncoding RNAs, epigenetics, vascular growth factors, oxidative stress, hemodynamic factors, and biomarkers play a pivotal role in the development of cardiorenal syndrome. It is therefore important to elucidate all the mechanisms in order to provide diagnostic and treatments tools. This review summarizes the hemodynamic and non-hemodynamic pathways along with biomarkers that could be the next target for diagnosis, treatment, and prognosis in cardiorenal syndrome. Cardiorenal syndrome represents a group of disorders resulting from the pathological interaction between the kidneys and the heart whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other .In 1836 Bright discussed the causal association between cardiovascular risk and chronic kidney disease. The passive renal congestion that results from cardiac dysfunction was named “rein cardiaque” in 1903 by french pathologist F. Justin Collet, while the term “cardiorenal syndrome” (CRS) was used in the 1940s to highlight the bidirectional interactions between the kidneys and heart .Cardiac dysfunction can determine injury on the kidney and reciprocally kidney injury will affect both the circulatory system and the heart. The causal relationship between chronic kidney disease, cardiovascular risk, and heart failure was demonstrated by clinical and epidemiological studies. More than 50% of all patients with chronic kidney disease have a 10- to-20-fold increased risk of cardiovascular disease compared to the same age non-CKD population . The oveThe cardiorenal syndrome classification has five subtypes that reflect primary and secondary pathology and simultaneous codysfunction secondary to the systemic condition . In 2008-Type 1 : acute decompensated heart failure causing acute kidney failure-Type 2 : chronic heart failure leading to kidney dysfunction-Type 3 (acute renocardiac syndrome): acute aggravation of kidney function causing heart dysfunction-Type 4 (chronic renocardiac syndrome): chronic kidney diseasegenerating heart dysfunction/disease -Type 5 : systemic conditions causing a simultaneous dysfunction of the heart and kidneys ,8.In addition Ronco et al. classified cardiorenal syndrome from type 1 to 5:For CRS to be diagnosed, it is relevant to highlight that both organ crosstalk is involved in acute and chronic pathogenesis and functional or structural abnormalities are present in the two organs  1]..1].Cardiorenal syndrome type 1 includes all conditions in which acute cardiac dysfunction causes acute kidney injury (AKI) .This syndrome represents an intricate condition where inflammatory and neurohormonal aspects create a vicious cycle. Pro-inflammatory cytokines produce apoptosis, oxidative stress, aggravate fluid retention and venous congestion . ConditiDuring CRS, type 1 and especially AKI, toll-like receptors (TLRs) play an important role in influencing inflammatory activation . There aNGAL or siderocalin is the first renal marker that could be detected in blood and urine after AKI . Ronco eCRS type 2 occurs when chronic abnormalities in cardiac function lead to kidney injury or dysfunction. Chronic hypoperfusion and renal congestion along with right atrial pressure represent a cornerstone in renal dysfunction of these patients .2 . . 29]. Despite the fact that the exact pathophysiology of CRS is unclear, a few mechanisms were proposed: increased central venous and abdominal pressure, reduced cardiac output, oxidative stress, and activation of the renin–angiotensin–aldosterone system (RAAS) . Increased intra-abdominal pressure (IAP), intra-abdominal hypertension (IAH), and increased central venous pressure (CVP) are closely correlated to renal function. A retrospective study on patients who underwent right heart catheterization revealed that increased CVP (>6 mmHg) was an independent and strong predictor of all causes of mortality and was also linked to impaired renal function . Sixty percent of patients with advanced chronic heart failure have increased IAP . In this group population, an IAP from 8–12 mmHg corresponds to renal dysfunction, leading to cardiorenal syndrome type 2. A decongestive therapy improves serum creatinine levels, reducing abdominal congestion .The two important mechanisms implicated in keeping the renal blood flow constant are: contraction/relaxation of the afferent vessels and the tubule–glomerular feedback. Several animal studies have indicated that a decisive role in renal dysfunction is attributed to an elevation in central venous pressure. Mullens et al. demonstrated that the development of the worsening of renal function in patients with advanced decompensated heart failure was lower for those with a CVP of <8 mmHg. Therefore, venous congestion has an important role in the onset of AKI. An elevated CVP leads to an increase in renal venous pressure (RVP) with consequences in glomerular filtration, worsening the cardiorenal syndrome .Severe depression of cardiac output, in conditions such as cardiogenic shock, leads to acute renal impairment specific for cardiorenal type 1. The activation of the adrenergic cascade in cardiogenic shock may cause ischemic effects  and also activation of the renin–angiotensin–aldosterone system in order to increase cardiac afterload .Moreover, in patients with heart failure, neurohormonal mechanisms that are activated to restore tissue perfusion such as the overactivity of the sympathetic nervous system result in increased renin levels from juxtamedullary kidney cells . High leThe symptoms and signs of hemodynamic abnormalities are probably the most incriminated manifestations of cardiorenal syndrome.The association between a reduced glomerular filtration rate with heart failure and its worst outcome has been shown in both HF with a reduced ejection fraction and with a preserved ejection fraction. Moreover, tricuspid valve regurgitation was associated with a lower estimated GFR.2i): improved glycemic control, reduced intra-glomerular pressure, and reduced intravascular volume. Cardiac resynchronization may improve cardiorenal status in patients with heart failure and CKD ), has antioxidant properties, protecting the kidneys and heart from the negative effects of oxidative stress .Inflammation has an important role in both acute and chronic cardiorenal dysfunction. Chronic kidney disease and chronic heart failure are clinical conditions with high levels of circulating inflammatory mediators.Activation of the endothelium has a direct effect on both inflammation and innate immunity, coagulation, complement activation, and platelet function .The neurohormonal imbalance, along with increased activity of the sympathetic nervous system and the renin–angiotensin–aldosterone system, volume overload, and venous congestion, represent biologic sources of chronic inflammation .Atherosclerosis, the link between chronic kidney disease and cardiovascular mortality and morbidity, is defined by a chronic inflammatory status at the vessel wall level, initiated by endothelial dysfunction. Chronic kidney disease activates vascular inflammatory processes and as consequence high levels of inflammatory biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor (TNF) are associated with an increased risk of myocardial infarction and mortality.In animal models, it has been demonstrated that oxidative stress, which is present in CKD patients, corresponds with an elevation in inflammatory markers.Recent clinical trials have shown the advantageous effect of sodium-glucose cotransporter-2 inhibitors in reducing oxidative stress with beneficial cardiovascular and renal effects.Another condition that could influence the circulating inflammation markers is malnutrition, frequently observed among CKD patients.Specific therapeutic targets for chronic inflammation are essential for improving patient outcomes.Inhibition of IL-1β was the interest subject of a randomized, double-blind placebo-controlled trial with over 10,000 patients, where a human monoclonal antibody that targets IL-1β (canakinumab) showed a reduction in recurrent cardiovascular events compared to the placebo .IL-6, one of the most studied cytokines, is associated with the progression of chronic heart failure, representing a predictor of all-cause mortality in this population group. Elevated levels are also present in chronic kidney disease, increasing with the worsening of the CKD stage .Pronounced monocyte activation is present in patients that are hospitalized with acute CRS (type 1 or 3) than hypertensive patients and/or end-stage renal disease .Age, a risk factor for cardiorenal syndrome, is associated with a pro-inflammatory state, representing a risk factor of several age-related pathologies, such as cardiovascular diseases and CKD. Chronic inflammation has an important contribution in both cardiovascular diseases and CKD evolution and progression. Proinflammatory biomarkers such as cytokines and chemokines discharged by the kidneys are implicated in the cardiovascular aging process observed in CKD patients.High levels of IL-6, TNF-α, and C-reactive protein have been associated with high mortality rates in the elderly. IL-6 has been considered a risk factor for left ventricular hypertrophy in peritoneal dialysis patients .Schunk et al. showed that IL-1α plays an important role in the development of CKD and cardiovascular diseases by regulating tissue accumulation of macrophages and neutrophils, promoting inflammatory injury. Inhibition of IL-1α could represent a future anti-inflammatory treatment target .Anemia is a common condition in patients with advanced HF and CKD with a prevalence in CRS from 5% to 55%, reported to be an independent predictor of mortality. Anemia contributes to the pathophysiology of CRS in several ways: can cause tissue ischemia and peripheral vasodilation (leading to activation of SNS), RAAS, the release of antidiuretic hormone , vasoconstriction, and chronic renal venous congestion . Moreover, the chronic anemic state causes left ventricular hypertrophy [ertrophy . Red bloertrophy .hyperuricemia may participate in the appearance and evolution of cardiorenal syndrome. High levels of uric acid are linked to oxidative stress, dysglycemia, insulin resistance, inflammation, cardiac diastolic dysfunction, and renal hyperfiltration—all components of CRS [Gathered evidence suggests that s of CRS . A low-ps of CRS .It is shown that intravenous iron therapy has an important role in the management of anemia in both patients with CKD and HF. Ten percent of patients with cardiorenal syndrome and anemia are guided for erythropoiesis-stimulating agent (ESA) therapy; ESA is not recommended for patients with anemia and HF. Further studies are needed to demonstrate the utility of hepcidin inhibition in the treatment of anemia for patients with cardiorenal syndrome .Obesity, through visceral adiposity , contributes to the onset of CRS and is associated with a greater risk for cardiorenal morbidity than subcutaneous adiposity. Obesity can lead to chronic kidney disease through mechanisms such as: hyperfiltration, increased glomerular capillary wall tension, and podocyte dysfunction. This leads to tubulointerstitial fibrosis and a loss of nephrons, cardiac remodeling, and interstitial fibrosis. Heart failure, with a preserved ejection fraction, is associated with obesity-related functional and structural abnormalities [malities . Obesitymalities .Because of the common vascularization of the cardiac and renal system, dysfunction within one system becomes a risk factor of dysfunction in the other .gut dysbiosis has been observed. It is unclear if gut dysbiosis is a potential cause or a downstream effect of cardiorenal syndrome, but one of the incriminated key contributors is uremic toxin accumulation, with cardiac, renal, and vascular effects. To limit internal production of uremic solutes, and to reduce circulating indoxyl sulfate levels, a low-protein diet was beneficial in chronic kidney disease patients along with the use of symbiotic therapy (prebiotic and probiotic) that showed positive modification of the stool microbiome [In both patients with heart failure and chronic kidney disease, crobiome .In cardiorenal syndrome, biomarkers have become increasingly prevalent in therapy, diagnosis, and prognosis. Studies on biomarkers have just begun and it is very important to note that detailed selection   and applp > 0.0007), with systolic function of the left ventricle  and with the glomerular filtration rate .It has been demonstrated that the severity of CRS is potentially linked to beta-2-microglobulin and tissue inhibitor of metalloproteinases 1 (TIMP 1) levels. Atici et al. found that levels of beta 2 microglobulin correspond to the cardiorenal evolution, proBNP levels , a promising representant of the beta-galactosidase-binding lectin family, interacts with proteins of the extracellular matrix such as: synexin, integrins, and laminin .Gal-3, after being released by the activated macrophages, induces the activation and deposition of collagen in the extracellular matrix ,75. Its Placental growth factor (PIGF) is another biomarker for CRS status assessment; a member of the vascular endothelial growth factor of cytokines with an important role both in CRS and in CKD alone.Another intriguing biomarker is urinary cofilin-1, a modulator of epithelial–mesenchymal transition, which is related to the severity of heart failure and is essential for AKI and renal function recovery .A promising approach towards intervention in CRS is the biomarkers that detect changes in collagen turnover in the extracellular matrix of the heart and kidneys. Biomarkers reflecting fibrosis such as Gal-3, NGAL, sST-2, and cardiotrophin-1, may be important in prognostication, early detection, and guiding the treatment of cardiorenal syndrome .In patients with hypertension and kidney injury, biomarkers of cell damage related to systemic oxidative stress such as 8-epi-isoprostanes and plasma thiobarbituric acid-reactive substances are elevated ,80. An eVascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and soluble vascular endothelial growth factor receptors-1 (sFlt-1) are elevated in patients with heart failure. sFlt-1 is a biomarker implicated in endothelial dysfunction in chronic kidney disease and connects microvascular disease with heart failure in CKD.Another biomarker, a member of the interleukin-1 receptor family, the soluble suppression of tumorigenicity-2 (sST2), is implicated in the development of CKD and is linked with cardiovascular events and survival in CKD patients, being also a tool for prognostic prediction in HF patients with renal dysfunction.Midregional proadrenomedullin (MR-proADM) is a promising biomarker that predicts the decline of renal function and morbidity in patients with HF .The liver-type fatty acid-binding protein (L-FABP) is an important predictor factor of AKI, with high urinary levels being found in patients with heart failure and AKI.Arginine vasopressin (AVP) is a peptide with multiple implications in cardiorenal syndrome: causes arteriole vasoconstriction, increases vascular resistance, and promotes water reabsorption in the distal tubule of the kidneys. Several studies are investigating the role of the competitive, selective AVP receptor antagonist, tolvaptan, in cardiorenal syndrome. Copeptin, the C-terminal portion of the AVP, was shown to be associated with cardiovascular disease in patients with CKD .In cardiorenal crosstalk, the essential aim is to consider that patients with cardiorenal syndrome are not homogeneous. There are five types of cardiorenal syndromes, but billions of patients with different pathophysiological characteristics need individualized approaches.Future studies and trials are necessary to explore the one common and major pathological pathway responsible for renal and cardiac injury before the onset of symptoms. Therefore, the field of biomarkers continues to be a challenge, especially in type 5, where a systemic condition simultaneously produces cardiac and renal dysfunction.The complex pathophysiology of CRS remains a challenging field. The complex interaction between the heart and kidneys continues to open new pathways for discovering and exploring possible mechanisms. In order to improve diagnostic processes, treatment strategies, and prognostic for patients with cardiorenal syndrome, focusing on the pathophysiological process and biomarkers represent a warranted tool.Despite being a diagnostic key, biomarkers provide important prognostic information; their serum level has a direct impact on mortality. Understanding cardiorenal syndrome from endothelial dysfunction, fibrosis, and inflammation to epigenetics is essential and future studies are needed to encompass this vast pathology.


Nonetheless, postoperatively mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac index improved, and multivariable cox regression analysis at 2 years identified preoperative total bilirubin and temporary right ventricular mechanical circulatory support as independent risk factors for all-cause mortality but not TMR. Prior TMR has no impact on mortality or cardiovascular complications in patients with LVAD. The interactions and hemodynamic impact of transcatheter percutaneous mitral valve repair (TMR) have not yet been investigated in patients undergoing left ventricular assist device (LVAD) implantation, but hemodynamic adverse effects are feared in the combination of TMR and LVAD for altered mitral valve flow. This study investigated the hemodynamic interplay in combination of TMR and LVAD in 119 patients, and propensity score match analysis revealed no difference in both perioperative mortality and 2-year follow-up survival ( MitraClip procedure and LVAD implantation are increasingly performed to improve symptoms but also survival in end-stage heart failure. Nevertheless, in this context, nothing is known about the interplay of MitraClip and LVAD therapy, and rumors proclaim that prior MitraClip may impair LVAD inflow and decrease LVAD therapy effectiveness.This is the first study to analyze the impact of MitraClip in patients with LVAD in a clinical, but also 2-year follow-up setting, including invasive right heart catherization measurements and mortality. Our findings are substantiated through propensity score–matched analysis in the largest cohort investigated yet. We demonstrate safety of prior MitraClip implantation in patients undergoing LVAD implantation, and our results proclaim that MitraClip is not associated with worse outcome when LVAD is implanted, and we can show positive influence of LVAD regarding right heart hemodynamics encouraging colleagues to consider heart transplantation in these patients.Patients with prior MitraClip can unscrupulously undergo LVAD implantation, but further trials will have to validate significance of functional mitral regurgitation treatment prior to LVAD implantation in end-stage heart failure.Functional severe mitral regurgitation (FMR) is frequently observed in patients with advanced heart failure (HF). FMR in HF patients is common, and it is not only associated with increased HF symptoms, but also poor clinical outcome –3. ConveThis study is the first trial to investigate pre-, peri-, and postoperative hemodynamic parameters as well as clinical outcomes in LVAD HF patients with and without TMR.Data was retrieved from our prospectively maintained patient database, and this single-center study was approved by our Institutional Ethics Committee of Ruhr-University Bochum in Bad Oeynhausen, Germany. Informed consent has been obtained between 2016 and 2020 from all end-stage HF patients with severe functional mitral valve regurgitation (FMR) in our hospital that additionally received LVAD implantation with the HeartMate 3 (HM3) device . This is an observational prospective study, and medical decision for either TMR or LVAD implantation was made in the heart team independently from study participation. We conducted an all-comer study; all patients with TMR were enrolled; there were no study exclusion criteria for elevated mitral valve gradient after TMR. During HM3 implantation, no patient had TMR removal or explantation.Patients are divided into two groups: HF patients with FMR and HM3 implantation without TMR (group 1) and patients with HM3 and TMR (group 2). Patients with mitral valve stenosis without TMR , surgical mitral valve repair, or mitral valve replacement were excluded. Patients with mitral valve surgery simultaneously during LVAD implantation were also not considered. Follow-up data of clinical status, survival, and cardiovascular events were collected, including transplantation, death, stroke, arrhythmia requiring cardioversion, and VAD-related complications, and follow-up is completely available in all study patients enrolled. The clinical follow-up was closed after 2-year follow-up, and endpoints of this study were predefined as all-cause death or heart transplantation.All procedures were performed by experienced board-certified cardiovascular surgeons via median sternotomy or left thoracotomy. Concomitant surgical procedures included aortic valve replacement, tricuspid valve repair, ASD closure, or resection of left atrial appendage. Cardio-pulmonary bypass (CPB) was established in standard fashion through direct cannulation of the ascending aorta and both caval veins or the right atrium in the sternotomy approach or via left groin vessels for left thoracotomy approach. Warm blood cardioplegia was applied into the aortic root, and cross-clamping was used in cases with concomitant aortic valve replacement. All other procedures were performed in beating-heart technique.In all patients, intraoperative transesophageal echocardiography (TEE) was performed to ensure correct inflow cannulation position, and the cannula was placed in dumpling position to allow unobstructed LVAD inflow. The outflow cannula was anastomosed with an end-to-side running suture to the ascending or descending aorta using side-clamping in both sternotomy and left thoracotomy approach, respectively.Temporary mechanical circulatory support (MCS) for right heart failure was implemented by percutaneous cannulation of a femoral vein and anastomosis of an 8-mm vascular graft  to the pulmonary trunk, both connected via heparin-coated standard tubing using CentriMag system  with or without oxygenator .All TMR procedures were performed prior to LVAD implantation. Only patients meeting accepted and established published TMR criteria were eligible , 4. The t test for continuous normally distributed data. The Mann–Whitney U test was used for comparisons of non-parametric continuous data and Fisher’s exact test for categorical data. Survival and freedom from all-cause death were derived using the Kaplan–Meier method, and comparisons were made using the log-rank test. Patient characteristics of both the HM3 and TMR + HM3 group were further analyzed using propensity score match (PS) analysis with adjustments for the 5 major characteristics known to confound mortality in LVAD patients. Patients of the HM3 group were matched in a one-on-one basis to patients of the TMR + HM3 group through practice of propensity score calculations using the nearest-neighbor match without replacement, within a matching tolerance  of 0.20 and an absolute standardized difference of ≦ 10%. The rates of freedom from all-cause death in the matched cohort were generated using the Kaplan–Meier method, and comparisons were made using the stratified log-rank test. To estimate independent effects regarding all-cause death, Cox proportional-hazards regression analysis  was subsequently applied to the matched population to identify independent predictors of mortality. Candidate covariates were chosen based on current medical knowledge. A p value of < 0.05 was considered statistically significant, and all reported p values are two-sided. All statistical analyses were performed using R.Results are expressed as mean ± standard deviation (SD) or as median + 25th to 75th percentile interquartile range for continuous variables and frequency and percentage for categorical variables. Univariable comparisons were performed using Student’s paired or unpaired n = 92) and patients with TMR  (Table p = 0.050) and had worse left ventricular ejection fraction , while all other baseline characteristics revealed no statistically significant differences and therefore allow comparability of the two study groups (Table n = 47 patients (51%) and non-ischemic in n = 45 patients (49%) in group 1, as well as ischemic in n = 19 patients (70%) and non-ischemic in n = 8 patients (30%) in group 2 (p = 0.084). At the time of LVAD implantation, the mean distance from TMR was 26 months , and distribution of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile levels were comparable in both groups (p = 0.76). All patients underwent coronary angiography prior to LVAD implantation to assess coronary artery status, and only one patient in group 1 required concomitant coronary artery bypass graft surgery.A total of 119 patients with FMR undergoing HeartMate 3 LVAD implantation were identified for inclusion in this study during 2016 and 2020. All demographics and clinical characteristics are summarized in Table To minimize potential confounding effects of selection bias and to decrease variability of both groups, we performed propensity score (PS) matching for the two groups FMR + HM3 and TMR + HM3 for clinical characteristics. PS matching was executed for age, sex, body mass index, HF etiology, and INTERMACS level, resulting in 27 matched pairs in the two groups Fig. .Fig. 1GrPS preoperative attributes revealed a higher number of ICD implantation and history of stroke for group 2. Interestingly, patients in group 2 had significantly lower pulmonary artery pressure (PAP) and precapillary wedge pressure (PCWP) in comparison to group 1 (Table p < 0.001). Temporary mechanical circulatory support (MCS) for perioperative right heart failure was required in n = 8 patients (30%) in group 1 and in n = 7 patients (26%) in group 2 (p > 0.05). The 30-day mortality rate was n = 1 patient (3.7%) in group 1 and n = 2 patients (7.4%) in group 2, respectively, and all these patients needed temporary MCS for perioperative right heart failure. Causes of death were septic shock and multi-organ failure.All intraoperative characteristics are summarized in Table In PS-matched analysis, pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP) significantly declined in both groups in comparison to preoperative measures Tables  and 2. Lp = 0.87). No baseline characteristic reached statistical significance regarding survival prediction between the two groups during the 2-year follow-up , while patients that had received heart transplantation were censored in the follow-up analysis  in group 1 and 80% 95%CI 52.4–92.6%) in group 2, respectively  bleeding, and one patient developed LVAD pump infection. All three group 1 patients received urgent heart transplantation at 2, 3, and 22 months after LVAD implantation. In group 2, one patient developed progressive right heart failure and one suffered from substantial GI bleeding, and these two group 2 patients received urgent heart transplantation at 1.5 and 13 months after LVAD implantation.p = 0.0013). In PS-matched analysis, only preoperative total bilirubin level remained as an independent risk factor for mortality  , and left ventricular assist device (LVAD) implantation. No study has analyzed the interplay or reciprocal interference of the two therapies yet, and our study further includes invasive pre-, peri-, and post-surgical hemodynamics as well as a 2-year follow-up mortality analysis. In addition, this study evaluated TMR impact on perioperative complications during LVAD implantation and investigated all interactions during the 2-year follow-up.We found no statistically significant interplay of TMR in patients undergoing LVAD implantation. TMR had no adverse or downside effect in our study, not even through propensity score match analysis. Nevertheless, TMR appeared to have beneficial purposes with reduced pulmonary artery pressures and lower pulmonary capillary wedge pressures in the TMR study group.Mortality after LVAD implantation is comparable in patients with and without TMR. TMR and untreated functional severe mitral valve regurgitation were both predictors of mortality. Only periprocedural right ventricular mechanical support and preoperative bilirubin remained as independent predictors of mortality in this trial.In line with current literature on durable MCS, our current data indicates that right heart failure and the necessity for temporary MCS trigger adverse outcome –9. Many Inclusion of additional HF comorbidities is essential in the context of mortality, and liver dysfunction has been acknowledged as a clear risk factor for outcome before , and ourFor the lively discussion whether patients with end-stage HF would benefit from TMR in conjunction with the necessity of LVAD implantation, our study now demonstrates not only endured TMR efficacy and safety for the combination of TMR and LVAD with no relevant complications in this setting during a 2-year follow-up period, but we can also show potential benefit for combining TMR and LVAD, because our study group of TMR and LVAD had reduced pulmonary artery pressures and lower pulmonary capillary wedge pressures, which is of importance when it comes to heart transplantation . CombiniHereafter, our study does not confirm previous findings indicating that TMR would negatively interfere with LVAD performance , 16. In Nevertheless, our study design does not allow to draw conclusions whether TMR could accelerate HF progression in LVAD as suggested before , questioOur study results add to the present controversial discussion on whether severe functional mitral regurgitation requires treatment in patients eligible for LVAD implantation . We cannInterestingly, survival after LVAD implantation is better in our trial 81.4%) than reported in the COAPT trial after TMR (71.8%) [% than reA small case series of Ammirati et al. describes six patients with TMR undergoing LVAD implantation, and two patients in that study underwent subsequent heart transplantation . Three pWhen not only regarding mortality in this exquisitely vulnerable end-stage HF patient population, we identified right heart failure with indication of temporary right ventricular mechanical support, as well as perioperative bilirubin to predict outcome, but not TMR, clearly representing the complexity of accompanied comorbidities in these patients –23.Therefore, more investigations are needed to elucidate optimized treatment strategies for both end-stage heart failure and functional mitral valve regurgitation, with taking notice of important accompanying comorbidities in this growing and scarcely studied patient population.This is a single-center observational study with a limited number of patients. Due to the design of our study, it may miss confounding factors that could potentially have influenced our results. Thus, conclusions from our study should be interpreted with caution until confirmed by large prospective and randomized clinical trials.In patients with TMR, HeartMate 3 LVAD implantation was safe and not affecting LVAD function as well as adverse events such as mortality in a 2-year follow-up, while TMR significantly improved right heart hemodynamics. Temporary right ventricular mechanical support is a predictor of mortality, while in propensity score match analysis, preoperative bilirubin is the only remaining predictor of mortality in this patient population.


Proximal protection devices, such as the Mo.Ma system provides better neurological outcomes than the distal filter system in the carotid artery stenting (CAS) procedure. This study first evaluated the safety and efficacy of the Mo.Ma system during CAS in a single tertiary referral hospital from Taiwan. The outcomes of distal vs. proximal embolic protection devices were also studied.A total of 294 patients with carotid artery stenosis who underwent the CAS procedure were retrospectively included and divided into two groups: 152 patients in the distal filter system group and 142 patients in the Mo.Ma system. The outcomes of interest were compared between the two groups. The factors contributing to occlusion intolerance (OI) in the Mo.Ma system were evaluated.p = 0.419). Patients with hypoalbuminemia significantly predicted the risk of stroke with an odds ratio of 0.08  per 1 g/day of serum albumin in the filter group. A total of 12 patients developed OI in the Mo.Ma system . Low occlusion pressure predicted the occurrence of OI in the Mo.Ma group with the hazard ratios of 0.88 (95% CI: 0.82–0.96) and 0.90 (95% CI: 0.84–0.98) per 1 mmHg of occlusion systolic pressure (OSP) and diastolic pressure (ODP), respectively. We further indicated that patients with an OSP of ≥60 mmHg or an ODP of ≥44 mmHg could tolerate the procedure of occlusion time up to 400 s, while patients with an OSP of <49 mmHg or an ODP of <34 mmHg should undergo the procedure of occlusion time less than 300 s to prevent the occurrence of OI.The procedure success rates were more than 98% in both groups. No major stroke occurred in this study. The minor stroke rates were 2.8% (4/142) and 4.6% (7/152) in the Mo.Ma system and filter system, respectively (We have demonstrated the safety and effectiveness of the Mo.Ma system during CAS in an Asia population. By reducing the occlusion time, our study indicated a lower risk of OI in the Mo.Ma system and proposed the optimal occlusion time according to occlusion pressure to prevent OI during the CAS procedure. Further large-scale and prospective studies are needed to verify our results. There were no significant differences in the 5-year follow-up of stroke-free survival between the CAS and CEA groups  in the Chinese population in a single tertiary referral hospital. Moreover, the predictors of occlusion intolerance (OI) as well as strategies to prevent OI in the Mo.Ma system during the CAS procedure were evaluated.The Institutional Review Board of Cheng Hsin General Hospital has approved this study (IRB No. 880-110-26). We included patients who received CAS in Cheng Hsin General Hospital in Taiwan from October 2008 to March 2021, which with symptomatic carotid artery stenosis with ≥60% stenosis and asymptomatic carotid artery stenosis with ≥80% stenosis based on the recommendations of CAS from The Ministry of Health and Welfare of Taiwan. Symptomatic carotid stenosis is defined as stenosis in the ICA, leading to symptoms of amaurosis fugax, transient ischemic attacks, or ischemic stroke ipsilateral to the lesion. Our study also included patients with syncope, blackouts, and fainting without other significant causes. Additionally, carotid artery stenosis following radiotherapy, carotid artery dissection resulting in stenosis or dissecting aneurysm, and patients with high CEA risks were also included. The severity of stenosis was measured by the North American Symptomatic Carotid Endarterectomy Trial (NASCET)  carotid via a femoral approach or a trans-radial approach under local anesthesia. After the femoral artery or radial artery was successfully punctured, we inserted a 6F arterial sheath. Heparin was administered intravenously at a dose of 100 units/kg to maintain an activated clotting time ≥300 s. We used the diagnostic catheters Judkins left (JL) and Judkins right (JR) for coronary angiography and used the JR diagnostic catheter for selected carotid and vertebral artery angiography. We performed the target vessel angiography at the last step of diagnostic angiography and maintained the catheter at the CCA. After confirming the severity of carotid artery disease, we advanced an angled Radifocus guidewire  through the JR diagnostic catheter to the ECA and then pushed the JR diagnostic catheter into the ECA. We exchanged a 0.035-inch Amplatz super-stiff wire  for the angled Radifocus guidewire, and then removed the JR catheter. Subsequently, we exchanged the 9F sheath for the 6F arterial sheath and inserted the Mo.Ma catheter and then advanced it with the tip of the catheter to the proximal ECA at approximately 1 cm beyond the carotid bifurcation. Angiography was performed to confirm the proper position of the Mo.Ma system. To reduce the balloon occlusion time and prevent OI, we preloaded a 0.014” guidewire and a selected carotid stent at the level of the CCA within the Mo.Ma catheter before the balloon occlusion of ECA and CCA if we planned to deploy the stent directly. Likewise, we placed a guidewire and balloon catheter at the level of the CCA within the Mo.Ma catheter in advance if we considered the pre-dilatation of the lesion.All the patients undergoing CAS took dual antiplatelet agents at least 7 days before the procedure. We undertook the CAS procedure mainly We inflated the balloon in the ECA of the Mo.Ma system by using 1:1 contrast medium  and saline solution for obstructing the retrograde flow from the ECA to the ICA. We inflated the ECA balloon to just cover or proximal to the origin of the superior thyroid artery. Angiography was performed to confirm the complete occlusion of ECA. Subsequently, we inflated the proximal balloon in the CCA to occlude the CCA. The occlusion of ECA and CCA flow was indicated by the change in balloons’ shape from circular to cylindrical. We recorded the established back pressure value as the occlusion pressure. Meanwhile, we made an angiography to confirm the stationary flow in the CCA and ICA. Then, the guidewire crossed the lesion and was advanced to the distal extracranial ICA. We predilated the lesion with a 3.0–3.5-mm semi-complaint balloon, and the stent was deployed if the lesion was considered too tight to directly cross a stent for deployment. Subsequently, stent post-dilatation with a 5.0 or 5.5-mm Sterling balloon  was performed. During the balloon dilatation of the carotid stenosis, the heart rate and blood pressure might be decreased due to carotid baroreceptor response. We informed the patients before the balloon inflation regarding the brief feeling of swelling or pain in the neck, and we administered atropine to block the baroreceptor response, which is effective for maintaining optimal blood pressure and heart rate during balloon dilatation. Only a minority of patients need a low dose of vasopressor dose to maintain stable hemodynamics after the procedure. Thereafter, a 30-ml Luer lock syringe aspirated the blood-containing debris through the central lumen of the Mo.Ma catheter immediately and filtered the blood through the sieves until there was no more debris. There were three aspirations with a total of 60–75 ml of blood aspirated for all our cases. We deflated the ECA balloon first, followed by the CCA balloon. We then pulled the jailed ECA balloon down to the CCA. Finally, post-stenting carotid angiography and ipsilateral intracranial angiography were performed. The femoral artery access site was closed by a vascular closure device .We retrospectively reviewed the data including sex, age, baseline comorbidities, and baseline biochemistry data and reviewed the pre-procedure carotid images and the CAS video. We stratified the patients into CAS with proximal Mo.Ma EPD and distal filter EPD. The two groups of patients were compared in terms of baseline characteristics and incidence of endpoints. We also evaluated the efficacy and safety of proximal Mo.Ma EPD.The outcomes of interest included procedural success, technical success, in-hospital stroke and death, and the rate of stroke and death at 6 months. We also assessed the balloon occlusion time, OI, and cerebral occlusion pressure of Mo.Ma proximal EPD. OI was defined as any transient neurological deficit observed during occlusion time with a complete recovery within 20 min after restoring antegrade flow . Occlusip < 0.05. The baseline characteristics were expressed as the mean ± SD or number (proportion) as appropriate, and the Student’s t-test and Chi-square test were used for statistical tests, respectively. The primary analysis included the risk of outcomes of interest in two groups, and the bar graphs were used to present and test by Fisher’s exact test due to the small sample size of events. We only additionally used logistic regression to analyze the risk factors for in-hospital stroke and 6-month stroke because the number of events was more than 5. Moreover, we used the Cox proportional hazard model to analyze the OI in the Mo.Ma group, which was censored at the end of the procedure to limit bias from faster cases. We also used the Kaplan–Meier curve to demonstrate the relationship between occlusion pressure and time to OI, and the tertile was used to group these patients. The Kaplan–Meier curve was based on the log-rank test, and the post hoc test was used by Bonferroni correction.Data were analyzed using R software version 3.4.4 and the statistical level was set as A total of 294 patients who underwent CAS were retrospectively collected. They were divided into two groups, the filter group and Mo.Ma group. p = 0.020) higher risk of stroke within 6 months, and the odds ratio was 0.08 (95% CI: 0.01–0.68) per 1 g/dl of serum albumin. p = 0.825) in the filter group (3.56 ± 0.39) and Mo.Ma group (3.55 ± 0.33), there were no potential confounding factors in further outcomes of interest comparison between these two groups.There were three and one failed procedures in the filter and Mo.Ma groups, respectively . One patpost hoc test shows that the risk of T1 was significantly higher than T2 (p = 0.023) and T3 (p = 0.023) in OSP analysis, but the difference between T2 and T3 was not significant (p = 0.937). Moreover, the results of the pairwise post hoc test in occlusion ODP analysis were not significant . Collectively, the T1 group shows higher risk of OI compared to the patients with higher occlusion pressure. There were no OI events before the first 200 s, and more than 20% of patients with systolic pressure of <49 mmHg presented with OI within 250 s. In contrast, the first event was presented at 400 s in patients with an OSP of ≥60 mmHg. Importantly, all patients with an occlusion ODP of <34 mmHg presented OI after 520 s, which provides the recommended procedure time for patients with different OSPs and ODPs. All the results proposed that patients with OSP of ≥60 mmHg or occlusion ODP of ≥44 mmHg could tolerate the procedure of occlusion time up to 400 s, while patients with OSP of <49 mmHg or occlusion ODP of <34 mmHg should undergo the procedure of occlusion time less than 300 s to prevent the occurrence of OI.In the application of the Mo.Ma EPD system, the procedure time is an important issue because the stationary carotid blood flow may result in OI during the CAS procedure. There were a total of 12 patients who developed OI in our study . We then evaluated the factors contributing to OI . All 12 By retrospective analysis of cohort data from a tertiary referring hospital, we demonstrated that the Mo.Ma system is non-inferior to the distal filter system regarding the procedure success rate, stroke, and mortality in patients with carotid artery stenosis. Although it may result from the respective design without randomization, we adjusted the factors of gender and age in the further analysis. Hypoalbuminemia significantly predicts the risk of 6-month stroke among patients undergoing distal filter procedures. Importantly, in the Mo.Ma group, patients with low occlusion systolic or ODP had a higher risk of OI than those with high occlusion systolic or ODP. The analysis of the time-events curve of OI clearly indicated that patients in the group of optimal high OSP or ODP could have more occlusion time of up to 400 s to finish the procedure. However, the occlusion time should be shortened to less than 300 s in patients with OSP of <49 mmHg or occlusion ODP of <34 mmHg to prevent the occurrence of OI.The procedure success rates were more than 98% in both the filter and Mo.Ma systems in our study with stroke rates of 4.6 and 2.8% in the filter system and Mo.Ma system, respectively, which is compatible with previous randomized control trials for CAS . Althougvia Acom and tight stenosis of the target vessel were not predictors for OI. Such discrepancies may be due to different study populations, which need investigations with multicenter and randomized control trials.We showed that the group of systolic occlusion pressure <49 or diastolic <34 mmHg significantly predicts the occurrence of OI, which is consistent with a previous study, indicating that low occlusion pressure is associated with the risk of OI . In the We found that patients with high occlusion pressure (OSP of ≥60 mmHg or occlusion ODP of ≥44 mmHg) could tolerate the procedure of occlusion time up to 400 s without the occurrence of OI, while more than 20% of patients with low occlusion pressure (OSP of <49 mmHg or occlusion ODP of <34 mmHg) presented with OI at the occlusion time within 250 s. A study from Giugliano et al. suggested that in the condition of mean occlusion pressure above 40 mmHg, the group with an occlusion time of more than 300 s was significantly associated with OI compared to the group with an occlusion time of less than 300 s . InteresPrevious studies have shed light on possible mechanisms linking occlusion pressure and the occurrence of OI. Occlusion pressure, measured in the ICA after the inflation of the balloons in the common and external carotid arteries, is represented as the perfusion pressure. The measurement of distal ICA pressure has been applied to predict ischemia in the procedures of CEA or permanent occlusion of the ICA for the treatment of complex cerebral aneurysms . Low perIn our study, the average plasma albumin levels were 0.53 mmol/L, which is in the low limit of normal ranges (0.53–0.83 mmol/L). There is no statistical significance in plasma albumin levels between the filter group and Mo.Ma group . By logiThere are some limitations in our study. First, this is a single-center retrospective study, and potential bias could not be completely controlled. Moreover, the limited patient population might be a concern for outcome analysis. Second, the CAS procedure is operator-dependent. The experience of an interventionalist significantly affects the procedure outcome, which cannot be extrapolated to all patients. Third, the lesion complexities and plaque morphologies, which might influence the outcomes, were not evaluated in the study. Fourth, DWI of brain MRI to detect silent brain infarcts was not performed. Fifth, in a systemic review, the rates of in-stent restenosis >50% are 3.9 and 5.7% at 6 and 12 months after CAS, respectively. A recent meta-analysis showed that CAS had a higher risk of restenosis (>50%) than CEA and a similar risk of severe restenosis (>70%) with CEA . Our stuCollectively, our study proposed the safety and efficacy profiles of the Mo.Ma system in a Chinese population. We showed that compared with the distal filter system, the Mo.Ma system exhibited compatible performance in successful procedures, stroke, and mortality. Most importantly, low occlusion systolic or ODP was the single significant factor predicting the risk of OI among patients undergoing the Mo.Ma procedure. Although further prospective and large-scale studies are needed to prove our results, we first recommended that patients with OSP of ≥60 mmHg or occlusion ODP of ≥44 mmHg could tolerate the occlusion time of 400 s, while patients with OSP of <49 mmHg or occlusion ODP of <34 mmHg should reduce the occlusion time to less than 300 s to prevent the occurrence of OI.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Institutional Review Board of Cheng Hsin General Hospital (IRB No. 880-110-26). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.C-CC, C-SL, Y-FL, and T-PT participated in the research design and wrote the manuscript. T-PT performed the experiments and was the principal investigator of this project. CL performed the statistical analysis. All authors interpreted the data, contributed to the editing of the manuscript, and gave the final approval of this manuscript.


Difficulties in first-principles calculations, such as density functional theory (DFT), emphasize the need for well-characterized experimental data. Here, we measure in-situ x-ray diffraction of shocked samarium (Sm) and temperature along the Hugoniot for the first time, providing direct evidence for phase transitions. We report direct evidence of a distorted fcc (dfcc) phase at 23 GPa. Shocked samarium melts from the dfcc phase starting at 33 GPa (1333 K), with complete melt at 40 GPa (1468 K). Previous work indicated shock melt at 27 GPa (1200 K), underscoring the significance of x-ray measurements for detecting phase transitions. Interestingly, our observed melting is in sharp contrast with the melting reported by a diamond anvil cell study. These experimental data can tightly constrain first principles calculations and serve as key touchstones for equation of state modeling.Lattice and electronic structure interactions for  Recent studies on cerium1 and samarium monochalcogenides2 demonstrate the difficulties in modeling lanthanides with first-principles methods due to their complex electronic and lattice structures. As such, direct structural insights play a vital role in understanding the underlying physics. Traditional shock wave experiments rely on the change in the slope of the shock and particle velocities to infer phase transitions, which can be misleading without direct structural evidence. The recent application of advanced light sources to dynamic x-ray diffraction enable observation of real-time structural changes and melting10 in a way that until now was out of reach.Constraining phase dynamics and melting in lanthanides with in-situ techniques offers a unique opportunity to study the interplay between complex electronic and lattice structures. Equation of state (EOS) measurements combined with phase information are essential to understanding material properties at various conditions, shedding light on the effect of (hR9)(hP4)(cF4)(hR24)hP3 is observed at increasing pressure13. Previous shock experiments on Sm interpreted a kink in the shock-particle , follow a similar sequence of phase transformations under increasing pressure: hexagonal closed packed (hcp) 15 is in fact a solid-solid transition. The onset of melting actually occurs at 33 GPa and completes by 40 GPa. These results provide important focal points to tightly constrain first principle calculations, allowing valuable insights in understanding material properties in f-electron systems.This paper presents the first dynamic structural study of Sm up to a maximum pressure of 75 GPa along the principal Hugoniot through melting, showing contrasting, but precise, evidence of a complete melt at 40 GPa. We observe the existence of a solid dfcc phase at 23 GPa, which remains stable up to 33 GPa. Importantly, the direct structural evidence observed in this study further clarifies that the kink observed in the R-3m)16. Note that the diffraction patterns observed in the current study exhibit characteristic peak broadening compared to the simulated patterns (dotted patterns), due to the width and asymmetry of the pink x-ray (non-monochromatic) beam. Nonetheless, all of the diffraction peaks corresponding to the Sm-type phase are still present.We have performed several experimental runs at the Dynamic Compression Sector (DCS), at the Advanced Photon Source (APS) using the experimental setup shown in Fig. Upon shock loading Sm to 23 GPa, a different solid phase is observed. The measured diffraction pattern suggests a presence of dfcc phase. Since at lower pressure an fcc phase of Sm is stable, we performed Rietveld refinement using the fcc structure, as well. Interestingly, the refinement results do not favor an fcc phase. Upon using dfcc structure for refinement, the overall fit is significantly improved, hence indicating that dfcc is the favored phase between the two. On the other hand, when fcc structure is used, several mismatches in (i) the width of the intense peak at 2.5 Å, (ii) intensities of the peak at 2.5, 2.2 and 1.5 Å, and (iii) the underestimation in the resultant fits of the overall pattern suggest that fcc structure is not the best candidate for the pattern at 29.1 GPa. This suggests that distorted-fcc is the favored state at these pressures.c/a ratio obtained from this study. The c/a ratio continuously increases with increasing pressure, which is consistent with the results from DAC studies11. If this structure were to be identical to an ideal fcc material with atoms located at  and , the expected c/a ratio would be c/a ratio deviation with increase in pressure, to conclude the favorability of the dfcc phase over the fcc phase.Another clear signature to support the determination of a distorted fcc structure rather than an ideal fcc structure is that the c/a ratio determined from the experimental data is greater than 2.45. Figure .45 Fig. a, and Ric-axis seems to be more sensitive to change in pressure than the a-axis, which makes sense as the lattice is stacked along the c-direction.Figure et al.17 data at ambient temperature. Note that only selected major lines from Zhao et al.17 data is shown. At 33.8 GPa, we observe an abrupt disappearance of the crystalline features, indicating the presence of a new phase. Rather than sharp peaks, two broad features at 2.4 Å and 1.3 Å are observed, consistent with the diffuse scattering expected from a liquid, suggesting an onset of melting.Figure We present additional evidence for the co-existence of the solid-liquid phase in the behavior of the Full-Width-Half-Maximum (FWHM) and the intensity ratios Fig. b of thes10. The peaks contributing from the ambient phases were taken into account. Based on the presence of a much narrower and more symmetrical peak between 33-38 GPa, we conclude that a solid dfcc phase and liquid phase co-exist over this regime. In contrast, above 40 GPa, much broader peaks indicate the presence of a fully melted phase. In this study, we observe clear diffraction patterns with both solid and liquid scattering contributions between 33 and 40 GPa, suggesting the co-existence of solid and liquid.Upon deconvolution of the features Fig. b inset, P-T space  in Fig Figure et al.15 have previously interpreted melting to occur based on the kink they observed in the Figure et al.15. We observe a small deviation in the density measurements of the dfcc+liquid phase using x-ray diffraction data, likely due to the additional peak broadening resulting from the presence of the liquid phase. The extraction of density from the liquid phase remains a challenge to date.The observed d-spacings from the x-ray diffraction data allow for determination of the lattice parameters of the dfcc phase. The resulting unit cell volume in turn enables determination of density. Figure 22, cerium23, and aluminum24. In the case of copper, Hayes et al.22 do not observe discontinuity along the Hugoniot. However, sound speed measurements on the other hand show a clear discontinuity upon melting. Therefore, x-ray diffraction or sound speed measurements are critical to pin down the exact phase transition stress, underscoring the significance of the current study in determining the phase boundary.We note that there is no abrupt change in the density (determined from impedance matching) observed upon liquid transition. This could be due to the fact that the volume change associated with a phase transformation of a material under shock loading conditions is not always obvious through Hugoniot measurements. This can be seen from many previous works on shock compressed metals, such as, copperet al.14 DAC heating study. In their study, melting was identified visually by the motion in the interference pattern created on the sample surface by Ar laser radiation using a 30 µm diameter hotspot created by defocused laser beams25. Needless to say that there could be quite a bit temperature gradient from the unheated sample. In fact, a careful study done by Karandikar et al.26 on Ta has shown that the previous melting reported by Errandonea et al.27 using similar methods as they employed on Sm has shown a 500 K discrepancy on Errandonea’s melting curve. It is quite likely that the temperature measurements were taken upon completion of the melt, hence, the upper end of the melting curve is measured. The much lower melting we observed in our study posits that more careful high temperature studies are needed in order to further constrain the melting curve of samarium.Our study shows that the dfcc phase is stable at higher temperatures between the pressure of 23-33 GPa, followed by a mixture of dfcc+liquid (33 to 38 GPa). Melting begins at 1333 K and is complete above 1468 K. The onset of melting we observe in our current study is 800 K lower temperature than that of Errandonea et al.study15 and this current study. Our results show a plateau between 30–38 GPa, consistent with the coexistence of dfcc+liquid phase. Melting begins at 1333 K and is complete above 1468 K. Upon completion of melt, there is a monotonous increase in temperature with increase in pressure. Our observed melting in current study is 800 K lower than that reported by the Errandonea et al.DAC study. Based on what we observe in our current study, it is likely that the melt curve of samarium has a negative slope as previously proposed by Rambert et al.13 (blue dashed line). Interestingly, similar trend of decreasing melt temperature with increase in pressure has been observed in other metals, such as, cerium23 and lithium28.Figure f-electron systems. Coupling shock compression with x-ray diffraction, we demonstrated the existence of the solid Sm dfcc phase above 23 GPa, which remains stable up to 33 GPa along the Hugoniot. Our XRD data combined with the temperature measurements establishes the onset of melting in Sm at 33 GPa, with liquid-solid coexistence up to 38 GPa. High-quality x-ray diffraction data indicate complete shock melting by 40 GPa. Our study provides key insights into understanding the phase behavior of Sm along the Hugoniot. Experimental data—more specifically, in-situ x-ray diffraction data and temperature measurements—are paramount to constrain these first-principles calculations and develop material models.Our study provides benchmark data to tightly constrain first-principles simulations for very complex 4 as a driver. We have performed in situ x-ray diffraction measurements in Sm using  23.54 keV x-rays. The two-dimensional x-ray diffraction rings were integrated azimuthally using DIOPTAS29 and FIT2D30 with poly-crystalline silicon as a calibrant to obtain one-dimensional diffraction profiles. The resulting one-dimensional profiles were then analyzed using Rietveld methods or by fitting the d spacings of individual diffraction peaks using a combination of various software, including GSAS-II31, VESTA32 and CRYSTALMAKER33.Diffraction experiments were performed at the Dynamic Compression Sector (DCS) at the Advanced Photon Source, using the 100 J laserOur targets were planar stacks consisting of a 50 Near-infrared optical pyrometry was used to infer temperature. Symmetric impact of a 25 mm diameter, 2 mm thick aluminum flyer with an identical buffer created an initial shock wave. A 15 mm diameter, 0.5 mm thick samarium sample was glued the buffer with AngstromBond, followed by a 25 mm diameter, 2 mm thick LiF window attached with Loctite 326 glue. Aluminum coating (front side) and black paint (outer edges and back side) minimizes stray light reaching the pyrometry probe, where a bundle of angle-polished optical fibers were imaged onto the sample. Four pyrometry measurements  were preformed with low-OH multi-mode fibers using avalanche indium gallium arsenide photodiodes.21. Measured radiance also increased at breakout, presumably due to fracture luminescence34.Pyrometry signals were converted to radiance via black body  calibration immediately before each experiment. Wavelength bands below 1000 nm were omitted from further analysis due to an obvious light flash in every experiment at the shock breakout. Figure 20 was used to further analyze steady-state temperature. Constant emissivity was assumed in each spectral band 36 with temperature. The former operates at 532 nm, while the latter operates at 1550 nm. Both measurements track motion of the Sm-LiF interface.Time-resolved optical interferometry was used all experiments: Velocity Interferometer System for Any Reflector (VISAR)37 and Sm15. The peak of the particle velocity traces  of 1.555 and 0.945 km/s. Ablation of the Kapton layer generated a shock that propagated into the Sm sample. Particle velocity measured at the Sm/LiF interface is linked to pressure by impedance matching to the previously reported Hugoniot for LiFces Fig.  were usePDV measurements used a frequency-shifted configuration to maintain several fringes over the 5 ns analysis duration. Three SMF-28 fibers in the imaged bundle provided redundant data to compensate for dynamic speckle effects. Quasi-steady values were used for impedance matching.39. In this technique, the wave profile measured at the Sm/LiF interface is used to determine an in-situ velocity in the Sm sample. This velocity can be related to waves propagating through the Sm sample by the method of characteristics, similar to that done in the Inverse Lagrangian Analysis40. By propagating the waves backwards using a compressed sound velocity, we were able to construct a map of pressure as a function of time and distance in the samples. From the pressure map, we could extract the pressure in the sample at the time of the x-ray image. Pressure maps and corresponding sample pressure distributions at the time of x-ray exposure are shown in Fig. To understand the pressure distribution in the sample at the time of the x-ray image, we have used the incremental impedance matching method to back-propagate the stress within the sampleFrom the sample pressure distributions, an overtaking wave from the front surface has propagated into the sample and released pressure by the time that the x-ray image was taken. This is especially noticeable for the highest-pressure shots (s235 and s329), where the 1