Left ventricular end-diastolic pressure response to spinal anaesthesia in euvolaemic vascular surgery patients.

PURPOSE: Regional anaesthesia techniques provide highly effective alternative to general anaesthesia. Existing evidence on the effect of spinal anaesthesia (SA) on cardiac diastolic function is scarce. This study aimed to evaluate the effects of a single-injection, low-dose SA on left ventricular end-diastolic pressures (LVEDP) using echocardiography in euvolaemic patients undergoing elective vascular surgery. METHODS: This is a prospective study in adult patients undergoing elective vascular surgery with SA. Patients with contraindications for SA or significant valvular disease were excluded. During patients' evaluations fluid administration was targeted using arterial waveform monitoring. All patients underwent echocardiographic studies before and after SA for the assessment of indices reflective of diastolic function. LVEDP was evaluated using the E/e' ratio. Blood samples were drawn to measure troponin and brain natriuretic peptide (BNP) levels before and after SA. RESULTS: A total of 62 patients (88.7% males, 71.00 ± 9.42 years) were included in the analysis. In total population, end-diastolic volume (EDV, 147.51 ± 41.36 vs 141.72 ± 40.13 ml; p = 0.044), end-systolic volume (ESV, 69.50 [51.50] vs 65.00 [29.50] ml; p < 0.001) and E/e' ratio significantly decreased (10.80 [4.21] vs. 9.55 [3.91]; p = 0.019). In patients with elevated compared to those with normal LVEDP, an overall improvement in diastolic function was noted. The A increased (- 6.58 ± 11.12 vs. 6.46 ± 16.10; p < 0.001) and E/A decreased (0.02 ± 0.21 vs. - 0.36 ± 0.90; p = 0.004) only in the elevated LVEDP group. Patients with elevated LVEDP had a greater decrease in E/e' compared to those with normal LVEDP (- 0.03 ± 2.39 vs. - 2.27 ± 2.92; p = 0.002). CONCLUSION: This study in euvolaemic patients undergoing elective vascular surgery provides evidence that SA improved LVEDP.

A systematic review and meta-analysis of proximal aortic neck dilatation after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: To provide an updated systematic literature review summarizing current evidence on aortic neck dilatation (AND) after endovascular aortic aneurysm repair (EVAR) in patients with infrarenal abdominal aortic aneurysm. METHODS: An extensive electronic search in major electronic databases was conducted between January 2000 and December 2021. Eligible for inclusion were observational studies that followed up with patients (n ≥ 20) undergoing EVAR with self-expanding endografts, for 12 or more months, evaluated AND with computed tomography angiography and provided data on relevant outcomes. The primary end point was the incidence of AND after EVAR, and the secondary end points were the occurrence of type Ia endoleak, stent graft migration, secondary rupture, and reintervention. RESULTS: We included 34 studies with a total sample of 12,038 patients (10,413 men; median age, 71 years). AND was defined clearly in 18 studies, but significant differences in AND definition were evidenced. The pooled incidence of AND based on quantitative analysis of 16 studies with a total of 9201 patients (7961 men; median age, 72 years) was calculated at 22.9% (95% confidence interval [CI], 14.4-34.4) over a follow-up period ranging from 12 months to 14 years. The risk of a type Ia endoleak was significantly higher in AND patients compared with those without AND (odds ratio, 2.95; 95% CI, 1.10-7.93; P = .030). Similarly, endograft migration was more common in the AND group compared with the non-AND group (odds ratio, 5.95; 95% CI, 1.80-19.69; P = .004). The combined incidence of secondary rupture and reintervention did not differ significantly between the two groups, even though the combined effect was in favor of the non-AND group. CONCLUSIONS: Proximal AND after EVAR is common and occurs in a large proportion of patients with infrarenal abdominal aortic aneurysm. AND can influence the long-term durability of proximal endograft fixation and is significantly related to adverse outcomes, often leading to reinterventions.

Asymmetric dimethylarginine correlates with worsening peripheral microangiopathy in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease characterized primarily by micro-angiopathy and endothelial dysfunction which stimulate a fibrotic process. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor and represents a novel biomarker for vascular dysfunction. Nailfold video capillaroscopy (NVC) represents a non-invasive and reliable technique for the evaluation of microvasculopathy in SSc. OBJECTIVES: The aim of this study was to examine the possible association between ADMA and microvascular involvement in patients with SSc. METHODS: This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA was measured in serum samples using a commercial enzyme immunoassay. Participants underwent NVC with qualitative and semi-quantitative assessment and all NVC parameters were measured in the distal row of each finger. The findings were classified in one of the three qualitative NVC patterns: early, active, and late. RESULTS: Eighty-one (92,6 % women) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. Within-groups comparisons revealed a trend between higher ADMA levels and progressive micro-vasculopathy (1,29 [2,1] vs 1,57 [1,95] vs 2,41 [3,87]; for early, active and late patterns respectively, p = 0.039). Furthermore, ADMA concentration was significantly associated with the number of capillaries/mm (r = -0.235; p = 0.035). CONCLUSIONS: Serum ADMA levels were significantly associated with advancing stages of microcirculatory abnormalities suggesting that ADMA may have a role in promoting microvascular endothelial dysfunction in SSc individuals.

Long-term Evaluation of Proximal Aortic Neck Dilatation After Endovascular Abdominal Aortic Aneurysm Repair With a Variety of Contemporary Endografts.

PURPOSE: To measure the long-term proximal aortic neck dilatation (AND) after elective endovascular aortic aneurysm repair (EVAR) with a variety of contemporary, third-generation, endograft devices. MATERIALS AND METHODS: This is a noninterventional prospective cohort study of 157 patients that underwent standard EVAR with self-expanding abdominal endografts. Patients' recruitment lasted from 2013 to 2017, and postoperative follow-up was up to 5 years. A computed tomography angiography (CTA) was performed at the first month and then at 1, 2, and 5 years. Proximal aortic neck's (PAN) basic morphological characteristics (diameter, length, angulation) were measured based on the analysis of CTA in a standardized fashion. Neck-related adverse events, such as migration, endoleak or rupture, and reinterventions were recorded. RESULTS: Significant straightening of the PAN was evident even in the first-month CTA with concurrent neck shortening that became significant at 5 years. Both the suprarenal aorta and the PAN significantly dilated overtime, with PAN dilating more progressively. Mean neck dilatation at the juxtarenal level was 0.8±0.4 mm at 1 year, 1.8±0.8 mm at 2 years, and 3.9±1.7 mm at 5 years, with a mean neck dilatation rate of 0.07 mm/month overall. The incidence of AND ≥2.5 mm was 37.2% at 2 years and 58.1% at 5 years after EVAR and was considered important (≥5 mm) in 11.5% of patients at 2 years and 30.6% of patients at 5 years. A multivariate analysis performed showed that the endograft oversizing, the preoperative neck diameter, and the preoperative abdominal aortic aneurysm sac diameter served as independent predictors of AND at 5 years. At the 5-year follow-up, 8 late type Ia endoleaks (6.5%) and 7 caudal migrations (5.6%) were identified, while no late ruptures were reported. In total, 11 late endovascular reinterventions (8.9%) were performed. Overall, proximal neck-related adverse outcomes (5/7 migrations and 5/8 endoleaks) and reinterventions (7/11) were significantly associated with the presence of important late AND. CONCLUSION: Proximal AND after EVAR is common. It can influence the long-term durability of proximal endograft fixation and is significantly associated with adverse outcomes, often leading to reinterventions. A systemic and extended surveillance protocol is needed for maintenance of good long-term results. CLINICAL IMPACT: This is a thorough and systematic analysis of the long-term geometric remodeling of the proximal aortic neck after EVAR, that highlights the importance of a strict, and extended surveillance protocol for maintenance of good long-term results of EVAR.

Early Results of Elective Endovascular Repair of Infrarenal Abdominal Aortic Aneurysms With the MinosTM Stent-Graft System.

PURPOSE: A variety of last-generation endografts are currently available for standard endovascular repair (EVAR) of infrarenal abdominal aortic aneurysms (AAAs). The purpose of this study is to report the preliminary clinical outcomes of the Minos trimodular stent-graft system, which was recently introduced to the European market. MATERIALS AND METHODS: Between February 2020 and 2022, we treated 41 consecutive AAA patients (mean age 72.2±8.5, 37 males) with elective standard EVAR using the Minos. The mean maximum diameter of AAAs was 54.7±6.6 mm, the mean proximal neck's (PN) diameter was 24.8±2.7 mm, while the relevant length and angulation were 16.0 mm and 21.7°, respectively. Overall, 22 (53.6%) patients presented with shorter and angulated PN, according to the stent-graft's instructions of use, and in 6 (14.6%) patients the PN angulation >60° was combined with concomitant iliac angulation >60°. Eleven (26.8%) EVARs were performed with concomitant enormous iliac artery narrowing and tortuosity. Finally, in 19 (46.3%) AAAs, the distal iliac landing zone was aneurysmatic and they were treated with the bell-bottom technique in 17 patients and with limb extension to the external iliac artery in two cases. We evaluated technical and clinical success of the index procedures, which was based on the combination of five factors: freedom from EVAR-related mortality, from graft-related endoleak of any type, from migration at any part of graft as well the absence of notable increase AAA's sac maximum diameter and the patency of bifurcated stent-graft and of access vessels. RESULTS: Primary technical and clinical success of index procedures was 100%. During a median 12-month radiological follow-up the clinical success remained 100%. No type I or III endoleak, stent-graft migration, EVAR-related death, AAA rupture, or graft-related adverse events or reinterventions were documented. Four (9.8%) type II endoleaks were detected with stable AAA sac diameter. The overall incidence of sac regression was 34.1% (n=14). CONCLUSION: The preliminary results of our series showed that Minos provided excellent feasibility and safety features even through angulated and tortuous iliac vessels and in short and angulated PNs. The overall clinical success at 1 year suggests that performance of Minos follows very high standards. Further validation of these promising results with long-term data is acquired to complete the evaluation of this recently introduced stent-graft system. CLINICAL IMPACT: The current study explored the clinical performance of a new in market ultra-low profile bifurcated abdominal aortic stent-graft, the MINOS. The early and 12-month results of study suggest that implantation of this stent-graft in standard EVAR, even in hostile proximal aortic neck and iliac vessels conditions, follows very high clinical standards and encourage the further clinical use of MINOS.

The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease.

OBJECTIVE: Endothelial dysfunction has been associated with increased cardiovascular events and overall mortality. Microvascular damage is prevalent both in diabetes mellitus (DM) and chronic kidney disease (CKD). Our aim was to compare microcirculatory function parameters in diabetic and non-diabetic CKD patients via nailfold video-capillaroscopy. METHODS: We included 48 diabetic and 48 non-diabetic adult CKD patients. All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia), and at the end of a 2-minute venous occlusion (congestion phase). RESULTS: Diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm2 , P = .022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm2 , P = .015). When stratified according to CKD stages, only in stage 3b capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline, during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm2 , P = .037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm2 , P = .022). CONCLUSIONS: Capillary density during postocclusive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory structural and functional impairment in CKD. These differences are more prominent in CKD stage 3b.

Accuracy of Peridialytic, Intradialytic, and Scheduled Interdialytic Recordings in Detecting Elevated Ambulatory Blood Pressure in Hemodialysis Patients.

RATIONALE & OBJECTIVE: Current recommendations suggest the use of ambulatory blood pressure monitoring (ABPM) as the gold standard for hypertension diagnosis and management in hemodialysis patients. This study assesses the accuracy of peridialytic, intradialytic, and scheduled interdialytic recordings in detecting abnormally elevated 44-hour interdialytic blood pressure (BP). STUDY DESIGN: Diagnostic test study. SETTINGS & PARTICIPANTS: 242 Greek hemodialysis patients who successfully underwent ABPM. TESTS COMPARED: Ambulatory BP was used as the reference method to evaluate the accuracy of the following BP metrics: predialysis and postdialysis BP, intradialytic BP, intradialytic plus pre/postdialysis BP, and scheduled interdialytic BP (on an off-dialysis day at 8:00 am, 8:00 pm, and their average). OUTCOME: 44-hour ambulatory systolic BP/diastolic BP (SBP/DBP) ≥ 130/80 mm Hg. RESULTS: The 44-hour SBP/DBP levels differed significantly from predialysis and postdialysis BP but showed no or minor differences compared with the other BP metrics. Bland-Altman plots showed an absence of systematic bias for all metrics but large between-method difference and wider 95% limits of agreement for predialysis and postdialysis BP compared with intradialytic, intradialytic plus pre/postdialysis, and averaged scheduled interdialytic BP. The sensitivity/specificity and κ-statistic for diagnosing 44-hour SBP ≥ 130 mm Hg were low for predialysis (86.5%/38.6%, κ-statistic = 0.27) and postdialysis BP (63.1%/73.3%, κ-statistic = 0.35), but better for intradialytic BP (77.3%/76.2%, κ-statistic = 0.53), intradialytic plus pre/postdialysis BP (76.6%/72.3%, κ-statistic = 0.49), and scheduled interdialytic BP (87.9%/77.2%, κ-statistic = 0.66). In receiver operating characteristic (ROC) analyses, the areas under the curve (AUC) of predialysis SBP (AUC = 0.723) and postdialysis SBP (AUC = 0.746) were significantly lower than that of intradialytic SBP (AUC = 0.850), intradialytic plus pre/postdialysis SBP (AUC = 0.850), and scheduled interdialytic SBP (AUC = 0.917) (z test, P < 0.001 for all pairwise comparisons). Similar observations were made for DBP. LIMITATIONS: Typical home BP data were not obtained, and no assessment was obtained of the reproducibility of the examined metrics over time. CONCLUSIONS: Intradialytic, intradialytic plus pre/postdialysis, and scheduled interdialytic BP measurements were more accurate in detecting elevated 44-hour BP than predialysis and postdialysis BP. Averaged intradialytic BP recordings or scheduled readings at the off-dialysis day appear to be promising approaches to the diagnosis of elevated BP in hemodialysis.

Volume overload in hemodialysis: diagnosis, cardiovascular consequences, and management.

Volume overload in haemodialysis (HD) patients associates with hypertension and cardiac dysfunction and is a major risk factor for all-cause and cardiovascular mortality in this population. The diagnosis of volume excess and estimation of dry weight is based largely on clinical criteria and has a notoriously poor diagnostic accuracy. The search for accurate and objective methods to evaluate dry weight and to diagnose subclinical volume overload has been intensively pursued over the last 3 decades. Most methods have not been tested in appropriate clinical trials and their usefulness in clinical practice remains uncertain, except for bioimpedance spectroscopy and lung ultrasound (US). Bioimpedance spectroscopy is possibly the most widely used method to subjectively quantify fluid distributions over body compartments and produces reliable and reproducible results. Lung US provides reliable estimates of extravascular water in the lung, a critical parameter of the central circulation that in large part reflects the left ventricular end-diastolic pressure. To maximize cardiovascular tolerance, fluid removal in volume-expanded HD patients should be gradual and distributed over a sufficiently long time window. This review summarizes current knowledge about the diagnosis, prognosis and treatment of volume overload in HD patients.

Can the assessment of ultrasound lung water in haemodialysis patients be simplified?

BACKGROUND: Lung ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. A semi-quantitative US score summing up the US-B lines (an equivalent of B lines in the standard chest X-ray) at 28 sites in the intercostal spaces (Jambrik et al. Usefulness of ultrasound lung comets as a non-radiologic sign of extravascular lung water. Am J Cardiol 2004; 93: 1265-1270) is the most used score. METHODS: We compared the prognostic performance for death, and cardiovascular (CV) events of the 28-sites US score with a score restricted to eight sites in a cohort of 303 haemodialysis (HD) patients. RESULTS: The 8- and the 28-sites scores were highly inter-related (Spearman's ρ = 0.93, P < 0.001), and their concordance index was fairly good (k = 0.79, 95% confidence interval 0.74-0.84). During a mean follow-up of 3 years, 112 patients died, and 129 experienced a CV event. At univariate and multivariate analysis, both scores were associated with mortality (P ≤ 0.01) and CV events (P ≤ 0.05). The explained variances (R2) for death and CV events of the 28-sites score in multivariate models including major risk factors for these outcomes in the end-stage kidney disease (ESKD) population were 3.9 and 2.2%, and those of the 8-sites score were 3.1 and 2.4%, respectively. The median time needed to perform the examination was 3.05 min [interquartile range (IQR) 2.22-5.00 min] for the 28-sites score and 1.35 min (IQR 1.16-2.00 min) for the 8-sites score. CONCLUSION: The 8-sites score is tightly related to the classical Jambrik 28-sites score and this score holds an almost identical predictive power to the reference score. Even though the 28-sites score can be completed just in ∼3 min, the 8-sites score requires only ∼1.30 min, and it is, therefore, better suited for application in everyday clinical practice in HD units.

The effect of admission and pre-admission serum creatinine as baseline to assess incidence and outcomes of acute kidney injury in acute medical admissions.

BACKGROUND: Acute kidney injury (AKI) in hospital-admitted patients is a common complication associated with increased mortality. The diagnosis of AKI relies on the ascertainment of peak increase in serum creatinine (SCr). This study evaluated the incidence of AKI using the increase from mean 7-365 days pre-admission (AKIpre) and admission (AKIadm) SCr levels, and examined the associations of AKI and changes in SCr levels with all-cause mortality. METHODS: A total of 2436 patients admitted to a tertiary hospital were recruited and followed-up for a median of 47.70 (interquartile range 18.20) months. AKI incidence and severity were defined according to the Kidney Disease: Improving Global Outcomes-AKI Guidelines. Follow-up data were collected from the Hospital Episode Statistics and Office of National Statistics. Mortality was evaluated during a short- (30 days), mid- (1 year) and long-term (4 years) period. RESULTS: No difference in the AKI rates using AKIpre and AKIadm (12.5% versus 12.2%; P = 0.695) or in the AKI severity (P = 0.261) was evident. Agreement between the two definitions was modest (Kappa-statistic = 0.596, P < 0.001). Patients with AKIpre or AKIadm had increased all-cause mortality compared with those without AKI during all follow-up periods. In fully adjusted regression analysis, AKIpre [hazard ratio (HR) = 2.226, 95% confidence interval (CI) 1.140-4.347; P = 0.027] and AKIadm (HR = 2.105, 95% CI 1.090-4.064; P = 0.027) remained associated with 30-day mortality. Results for the 1- and 4-year periods were similar. Increases of >4.00 µmol/L and >6.06% from pre-admission or >6.00 µmol/L and >17.24% from admission SCr levels presented increased mortality risk during follow-up. CONCLUSIONS: Use of admission or pre-admission SCr provides similar incidence rates, but they diagnose different sets of patients. Even minor increases in SCr, below those required for the classification of AKI, were associated with increased mortality. These findings can help the clinicians to identify patients at higher risk for adverse outcomes.

Blood pressure monitoring in kidney transplantation: a systematic review on hypertension and target organ damage.

BACKGROUND: Sparse studies show that ambulatory blood pressure monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population. METHODS: Major medical databases were searched for studies enrolling adult KTRs undergoing 24h ABPM compared to office or home BP measurements. Main outcomes were: associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed. RESULTS: Twenty-two studies (2078 participants) were reviewed. Amongst 12 studies collecting data on renal endpoints, ten studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine (SCr) and/or creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR), than traditional office measurements. Twelve studies analyzed the relation between different BP recordings and CV target organ damages and reported robust correlations between echocardiographic abnormalities [i.e. left ventricular mass index (LVM/LVMI)] and 24h ABPM, but not with office BPs. Furthermore, 24h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness (IMT), diffuse thickening, and endothelial dysfunction. Additionally, abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities. CONCLUSIONS: In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, altered circadian BP profile associated with renal and CV target organ damages.

The Effects of Nebivolol and Irbesartan on Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients with Intradialytic Hypertension.

BACKGROUND: Intradialytic hypertension occurs in 5-15% of hemodialysis patients and is associated with increased cardiovascular risk, but the responsible mechanisms remain unknown. This study examined the effects of nebivolol and irbesartan on ambulatory central blood pressure (BP), arterial stiffness, and wave-reflection parameters in patients with intradialytic hypertension. METHODS: This is a prespecified analysis of a single-blind, randomized, cross-over study in 38 hemodialysis patients with intradialytic hypertension. Patients were randomized to nebivolol 5 mg followed byirbesartan 150 mg, or vice versa. In a non-randomized manner, the first half of the patients (n = 19) received a single drug dose 1 h prior to dialysis session and the remaining received the drugs for a whole week before the evaluation. Ambulatory central BP, arterial stiffness, and wave-reflection parameters were estimated with Mobil-O-Graph NG device, during a midweek dialysis day. RESULTS: Intake of a single dose of nebivolol or irbesartan resulted in lower postdialysis central systolic BP (c-SBP) (baseline: 140.9 ± 15.4; nebivolol: 130.3 ± 19.5, p = 0.009; irbesartan: 127.3 ± 24.4 mm Hg, p = 0.007). Single-dose nebivolol also produced marginally lower 24-h c-SBP (p = 0.064) and lower 24-h central diastolic BP (c-DBP) (p = 0.029). Weekly administration of both drugs reduced postdialysis c-SBP (baseline: 144.1 ± 15.3; nebivolol: 131.8 ± 14.1, p = 0.014; irbesartan: 126.4 ± 17.8, p = 0.001) and 24-h c-SBP and c-DBP (baseline: 135.5 ± 10.3/91.9 ± 9.2; nebivolol: 126.4 ± 8.4/86.6 ± 7.2, p < 0.001/p = 0.002; irbesartan: 128.7 ± 11.6/87.0 ± 9.4, p = 0.061/p = 0.051 mm Hg). Single-dose intake of both drugs did not affect heart rate-adjusted augmentation index [AIx(75)], but decreased postdialysis pulse wave velocity (PWV). Importantly, weekly administration of both drugs reduced 24-h PWV (baseline: 10.0 ± 2.5; nebivolol: 9.7 ± 2.5, p = 0.012; irbesartan: 9.7 ± 2.7, p = 0.041). In between drug-group comparisons, no significant differences were noted. CONCLUSIONS: This is the first randomized evaluation on the effects of pharmacological interventions on central BP and PWV in patients with intradialytic hypertension. Weekly administration of both nebivolol and irbesartan reduced 24-h central BP and PWV, but not AIx(75).

Lung Ultrasound-Guided Dry Weight Assessment and Echocardiographic Measures in Hypertensive Hemodialysis Patients: A Randomized Controlled Study.

RATIONALE & OBJECTIVE: Left ventricular (LV) hypertrophy and dysfunction are associated with adverse outcomes in hemodialysis patients. Hypertension and hypervolemia play important roles in these cardiac abnormalities. We report on the prespecified secondary outcome, echocardiographic indexes of LV function, from a previously reported study of the effect of lung ultrasound (US)-guided dry weight reduction on systolic blood pressure. STUDY DESIGN: Single-blind randomized trial. SETTINGS & PARTICIPANTS: 71 clinically euvolemic hypertensive hemodialysis patients in Greece and Slovenia. INTERVENTION: The active intervention group's (n=35) volume removal was guided by the total number of lung US B-lines observed every week before a midweek dialysis session. The usual-care group (n=36) was treated using standard-of-care processes that did not include acquisition of US data. OUTCOMES: 2-dimensional and tissue Doppler echocardiographic indexes at baseline and study end (8 weeks) that evaluated left and right heart chamber sizes, as well as systolic and diastolic function. RESULTS: Overall, 19 (54%) patients in the active intervention and 5 (14%) in the usual-care group had ultrafiltration intensification (P<0.001) during follow-up; changes in US B-lines (-5.3±12.5 vs+2.2±7.6; P<0.001) and dry weight (-0.71±1.39 vs+0.51±0.98kg; P<0.001) significantly differed between the active and usual-care groups. Inferior vena cava diameter decreased in the active compared with the usual-care group (-0.43±4.00 vs 0.71±4.82cm; P=0.03) at study end. Left (LA) and right (RA) atrial dimensions decreased more in the active group (LA surface, -1.09±4.61 vs 0.93±3.06cm2; P=0.03; RA surface -1.56±6.17 vs 0.47±2.31; P=0.02). LA volume index nominally decreased more in the active group (-2.43±13.14 vs 2.95±9.42mL/m2), though this was of borderline statistical significance (P=0.05). Reductions in LV end-diastolic diameter and volume were marginally greater in the active group. The change in LV filling pressures was significantly different in the active compared with the usual-care group (early transmitral diastolic velocities ratio [E/e'], -0.38±3.14 vs 1.36±3.54; P=0.03; E wave deceleration time, 35.43±85.25 vs-18.44±50.69; P=0.002]. Systolic function indexes were unchanged in both groups. In multivariable analysis, US B-line reduction was associated with a reduction in the E/e' LV ratio (OR, 4.542; 95% CI, 1.266-16.292; P=0.02). LIMITATIONS: Exploratory study; small sample size. CONCLUSIONS: A US-guided strategy for dry weight reduction is associated with decreased cardiac chamber dimensions and LV filling pressure, but no difference in systolic performance compared with usual care in hypertensive hemodialysis patients. FUNDING: European Renal Association-European Dialysis and Transplant Association. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03058874.

Ambulatory Blood Pressure Trajectories and Blood Pressure Variability in Diabetic and Non-Diabetic Chronic Kidney Disease.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease worldwide. Whether diabetes mellitus (DM) is an additional factor leading to elevated blood pressure (BP) levels and BP variability (BPV) in patients with chronic kidney disease (CKD) is unknown. This study aimed to compare ambulatory BP levels, BP trends and BPV in diabetic and non-diabetic patients with CKD. METHODS: This study included 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (estimated glomerular filtration rate [eGFR] <90 and ≥15 mL/min/1.73 m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All patients underwent 24-h ambulatory BP measurement with the Mobil-O-graph device. To evaluate the effect of DM and time on the trajectories of 24-h BP levels, we performed two-way mixed ANOVA analysis for repeated measurements using hourly means. BPV was calculated with validated formulas. RESULTS: In total, patients with DM had significantly higher 24-h systolic BP (SBP; 132.13 ± 10.71 vs. 124.16 ± 11.45; p = 0.001) and pulse pressure (PP; 57.1 ± 9.6 vs. 49.5 ± 10.9; p < 0.001), but similar 24-h diastolic BP (DBP; 75.00 ± 8.43 vs. 74.62 ± 6.86 mm Hg; p = 0.809) compared to patients without DM. A similar trend was evident across all CKD stages. The effect of DM on BP trajectories during the recording period was significant for SBP (F = 18.766, p < 0.001, partial η2 = 0.261) and marginally significant for DBP (F = 3.782, p = 0.057, partial η2 = 0.067). Twenty-four hour SBP SD, weighted SD (wSD) and average real variability (ARV; 10.94 ± 2.75 vs. 9.46 ± 2.10; p = 0.004), as well as 24 h DBP SD, wSD, coefficient of variation (CV) and ARV (8.23 ± 2.10 vs. 7.10 ± 1.33; p = 0.002) were significantly higher in diabetic compared to non-diabetic CKD patients. CONCLUSIONS: Ambulatory SBP and PP levels are higher and SBP-profile is different in patients with diabetic compared to those with non-diabetic CKD. Systolic and diastolic BPV are also higher in diabetics. These findings may signify a higher cardiovascular risk for patients with both DM and CKD compared to patients with CKD alone, through higher BP levels and BPV.

The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood pressure in hemodialysis patients: a randomized controlled trial.

Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population.

The association of interdialytic blood pressure variability with cardiovascular events and all-cause mortality in haemodialysis patients.

BACKGROUND: Long-term pre-dialysis blood pressure variability (BPV) in haemodialysis patients is associated with increased cardiovascular risk. The association of the main haemodynamic culprit in dialysis, that is, short-term BPV, with outcomes has not been investigated. We examine the prognostic role of short-term BPV for mortality and cardiovascular events in this population. METHODS: A total of 227 haemodialysis patients underwent 44-h ambulatory monitoring during a standard interval and were followed-up for 30.17 ± 17.70 months. We calculated SD, weighted SD (wSD), coefficient of variation (CV) and average real variability (ARV) of BP with validated formulas. The primary endpoint was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary endpoints were: (i) all-cause mortality, (ii) cardiovascular mortality and (iii) a combination of cardiovascular events. RESULTS: Cumulative freedom from the primary endpoint was similar for quartiles of pre-dialysis and 44-h systolic BP (SBP), but was progressively longer for increasing quartiles of 44-h SBP-SD (P = 0.014), wSD (P = 0.007), CV (P = 0.031) and ARV (83.9, 71.9, 70.2 and 43.9% for quartiles 1-4; P < 0.001). Higher quartiles of 44-h SBP-ARV were associated with higher risk of all studied outcomes. Among diastolic BPV indices, 44-h diastolic BP (DBP)-CV and 44-h DBP-ARV were associated with increased risk for the composite cardiovascular outcome. In Cox regression analysis, SBP-BPV was related to the primary endpoint, independently of SBP levels and interdialytic weight gain [ARV: hazard ratio (HR) 1.115, 95% confidence interval (95% CI) 1.048-1.185]. This association become insignificant after adjustment for pulse wave velocity (PWV; HR 1.061, 95% CI 0.989-1.137), and further attenuated after additional adjustment for age, dialysis vintage, gender, comorbidities and prevalent cardiovascular disease (HR 1.031, 95% CI 0.946-1.122). CONCLUSIONS: Increased BPV during the interdialytic interval is associated with higher risk of death and cardiovascular events, whereas ambulatory BP levels are not. This association was not independent after adjustment for PWV, other risk factors and prevalent cardiovascular disease. Short-term BPV could be a mediator promoting the adverse cardiovascular profile of haemodialysis patients.

Prevalence and control of hypertension by 48-h ambulatory blood pressure monitoring in haemodialysis patients: a study by the European Cardiovascular and Renal Medicine (EURECA-m) working group of the ERA-EDTA.

BACKGROUND: Population-specific consensus documents recommend that the diagnosis of hypertension in haemodialysis patients be based on 48-h ambulatory blood pressure (ABP) monitoring. However, until now there is just one study in the USA on the prevalence of hypertension in haemodialysis patients by 44-h recordings. Since there is a knowledge gap on the problem in European countries, we reassessed the problem in the European Cardiovascular and Renal Medicine working group Registry of the European Renal Association-European Dialysis and Transplant Association. METHODS: A total of 396 haemodialysis patients underwent 48-h ABP monitoring during a regular haemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-haemodialysis blood pressure (BP) ≥140/90 mmHg or use of antihypertensive agents and (ii) ABP ≥130/80 mmHg or use of antihypertensive agents. RESULTS: The prevalence of hypertension by 48-h ABP monitoring was very high (84.3%) and close to that by pre-haemodialysis BP (89.4%) but the agreement of the two techniques was not of the same magnitude (κ statistics = 0.648; P <0.001). In all, 290 participants were receiving antihypertensive treatment. In all, 9.1% of haemodialysis patients were categorized as normotensives, 12.6% had controlled hypertension confirmed by the two BP techniques, while 46.0% had uncontrolled hypertension with both techniques. The prevalence of white coat hypertension was 18.2% and that of masked hypertension 14.1%. Of note, hypertension was confined only to night-time in 22.2% of patients while just 1% of patients had only daytime hypertension. Pre-dialysis BP ≥140/90 mmHg had 76% sensitivity and 54% specificity for the diagnosis of BP ≥130/80 mmHg by 48-h ABP monitoring. CONCLUSIONS: The prevalence of hypertension in haemodialysis patients assessed by 48-h ABP monitoring is very high. Pre-haemodialysis BP poorly reflects the 48 h-ABP burden. About a third of the haemodialysis population has white coat or masked hypertension. These findings add weight to consensus documents supporting the use of ABP monitoring for proper hypertension diagnosis and treatment in this population.

Increased Sclerostin, but Not Dickkopf-1 Protein, Is Associated with Elevated Pulse Wave Velocity in Hemodialysis Subjects.

BACKGROUND: Sclerostin and Dickkopf-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/ß-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in chronic kidney disease (CKD), but data on the effects of Dkk-1 are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. METHODS: A total of 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central blood pressure (BP), and wave reflections evaluated with applanation tonometry (Sphygmocor) on a midweek non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, comorbid, laboratory, and drug parameters were used in the analyses. RESULTS: Subjects with PWV >9.5 m/s (high arterial stiffness group, n = 40) were older, had higher BMI, higher prevalence of hypertension, diabetes, and coronary heart disease, and higher peripheral systolic BP, central systolic BP, C-reactive protein, and serum sclerostin (p = 0.02), but similar Dkk-1, compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63 ± 2.71 vs. 9.77 ± 3.13, p = 0.048). Increased sclerostin (>200 pg/mL) was significantly associated with increased PWV (>9.5 m/s; HR 2.778, 95% CI 1.123-6.868 per pg/mL increase); this association remained significant after stepwise adjustment for Dkk-1, intact parathyroid hormone, and calcium × phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR 1.000, 95% CI 0.416-2.403). CONCLUSION: Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast, Dkk-1 has no association with arterial stiffness and is not pathophysiologically involved in relevant vascular changes.

The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRD.

Cardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern; i.e., they occur more commonly during the last day of the long interdialytic interval and the first session of the week. The hemodialysis process causes acute decreases in cardiac chamber size and pulmonary circulation loading and acute diastolic dysfunction, possibly through myocardial stunning and other non-myocardial-related mechanisms; systolic function, in contrast, is largely unchanged. During interdialytic intervals volume overload, acid-base, and electrolyte shifts, as well as arterial and myocardial wall changes, result in dilatation of right cardiac chambers and pulmonary circulation overload. Recent studies suggest that these alterations are more extended during the long interdialytic interval or the first dialysis session of the week and are associated with excess volume overload or removal, respectively, thus adding a mechanism for the day-of-week pattern of mortality in patients receiving hemodialysis. This review summarizes the existing data from echocardiographic studies of cardiac morphology and function during the hemodialysis session, as well as during the interdialytic intervals.

Levels of Endocan, Angiopoietin-2, and Hypoxia-Inducible Factor-1a in Patients with Autosomal Dominant Polycystic Kidney Disease and Different Levels of Renal Function.

BACKGROUND: Endothelial dysfunction leading to unbalanced vasoconstriction and ischemia of renal parenchyma is increasingly proposed as an alternative pathway of renal damage in autosomal dominant polycystic kidney disease (ADPKD). However, human studies investigating the evolution of such phenomena are limited. This study investigated the levels of emerging biomarkers of endothelial function, angiogenesis and hypoxia, in ADPKD patients with different renal function. METHODS: The study population consisted of three groups: 26 ADPKD patients with impaired renal function (Group A; estimated glomerular filtration rate [eGFR] 45-70 mL/min/1.73 m2), 26 ADPKD patients with preserved renal function (Group B; eGFR >70 mL/min/1.73 m2), and 26 age- and sex-matched controls with no history of renal disease. Circulating levels of endocan (endothelial cell-specific molecule-1) angiopoietin-2, and hypoxia-inducible factor-1a (HIF-1a) were determined by enzyme-linked immunosorbent assay techniques. RESULTS: Patients in Group A had significantly higher levels of endocan (7.17 ± 0.43 ng/mL), angiopoietin-2 (5,595.43 ± 3,390), and HIF-1a (163.68 ± 37.84 pg/mL) compared to patients in Group B (6.86 ± 0.59 ng/mL, p = 0.017, 3,854.41 ± 3,014.30, p = 0.018, 136.84 ± 42.10 pg/mL, p = 0.019 respectively) or controls (4.83 ± 0.69 ng/mL, 1,069 ± 427.88 pg/mL, 70.20 ± 17.49 pg/mL, p < 0.001 for all comparisons). Of note, patients in Group B had also higher levels of all markers compared to controls (p < 0.001) despite having similar renal function. In correlation analyses within ADPKD patients, we noted strong correlations of all studied markers with asymmetric dimethylarginine (ADMA; endocan r = 0.908, p < 0.001, angiopoietin-2 r = 0.983, p < 0.001 and HIF-1a r = 0.998, p < 0.001), and only weak or modest correlations with eGFR. CONCLUSIONS: This study suggests that endothelial dysfunction causing microcirculatory changes, linked to angiogenesis and hypoxia, may come early in the course of ADPKD and could be a key regulator of renal injury progression.