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According to the European Hypertension Guidelines regarding office blood pressure measurements (OBPMs), the mean between second/third or third/fourth OBPM should be taken if the first two readings differ by ≤10 or >10 mmHg, respectively. Our aim was to explore the value of the fourth OBPM and determine whether a simplified OBPM procedure is feasible without loss of quality. In this cross‐sectional study, four standard OBPMs were taken. The mean of the second/third OBPM (S2S3/D2D3) and third/fourth OBPM (S3S4/D3D4) for systolic/diastolic values was calculated. Correlation, agreement, and differences regarding BP classification were explored for the entire cohort and subsets with a difference between the first/second OBPM (S1S2/D1D2) ≤10 and >10 mmHg. Overall (n = 802) and for the subsets with an S1S2 (n = 596) and D1D2 (n = 742) difference ≤10 mmHg, S3S4/D3D4 was in median 0.5 mmHg lower than S2S3/D2D3, respectively (p 10 mmHg, S3S4/D3D4 differed numerically from S2S3/D2D3, respectively (p > .1 for all). Overall and for all subsets with an S1S2/D1D2 difference ≤10/>10 mmHg, less subjects were numerically classified as hypertensive with S3S4/D3D4 than with S2S3/D2D3 (p > .04), but BP reclassification occurred in both directions in 1.0%‐10.0%, depending on the cohort. In conclusion, the third/fourth OBPM results in lower BP values than the second/third measurement, regardless of the difference between first/second OBPM, whereby BP reclassifications occurred in both directions. Therefore, the cutoff of >10 versus ≤10mmHg difference between first/second OBPM to implement a fourth BPM harbors the risk of distorted results. We therefore recommend using the second/third BPM for standardized OBPM. Trial registration: Registered on clinicaltrials.gov (NCT02552030).

A cuffless blood pressure (BP) device (TestBP) using pulse transit time is in clinical use, but leads to higher BP values compared to a cuff-based 24 h-BP reference device (RefBP). We evaluated the impact of a recent software update on BP results and TestBP’s ability to differentiate between normo- and hypertension. 71 individuals had TestBP (Somnotouch-NIBP) and RefBP measurements simultaneously performed on either arm. TestBP results with software version V1.5 were compared to V1.4 and RefBP. Mean 24 h (± SD) BP for the RefBP, TestBP-V1.4 and TestBP-V1.5 were systolic 134.0 (± 17.3), 140.8 (± 20) and 139.1 (± 20) mmHg, and diastolic 79.3 (± 11.7), 85.8 (± 14.1) and 83.5 (± 13.0) mmHg, respectively (p-values

Background Blood pressure measurement (BPM) is one of the most often performed procedures in clinical practice, but especially office BPM is prone to errors. Unattended automated office BPM (AOBPM) is somewhat standardised and observer-independent, but time and space consuming. We aimed to assess whether an AOBPM protocol can be abbreviated without losing accuracy. Design In our retrospective single centre study, we used all AOBPM (AOBPM protocol of the SPRINT study), collected over 14 months. Three sequential BPM (after 5 minutes of rest, spaced 2 minutes) were automatically recorded with the patient alone in a quiet room resulting in three systolic and diastolic values. We compared the mean of all three (RefProt) with the mean of the first two (ShortProtA) and the single first BPM (ShortProtB). Results We analysed 413 AOBPM sets from 210 patients. Mean age was 52±16 years. Mean values for RefProt were 128.3/81.3 mmHg, for ShortProtA 128.4/81.4 mmHg, for ShortProtB 128.8/81.4 mmHg. Mean difference and limits of agreement for RefProt vs. ShortProtA and ShortProtB were -0.1±4.2/-0.1±2.8 mmHg and -0.5±8.1/-0.1±5.3 mmHg, respectively. With ShortProtA, 83% of systolic and 92% of diastolic measurements were within 2 mmHg from RefProt (67/82% for ShortProtB). ShortProtA or ShortProtB led to no significant hypertensive reclassifications in comparison to RefProt (p-values 0.774/1.000/1.000/0.556). Conclusion Based on our results differences between the RefProt and ShortProtA are minimal and within acceptable limits of agreement. Therefore, the automated procedure may be shorted from 3 to 2 measurements, but a single measurement is insufficient.

OBJECTIVE Noninvasive thoracic bioimpedance by the HOTMAN System estimates hemodynamic modulators and expresses them as hemodynamic profiles. Aims of this analysis were to describe hemodynamic profiles among treatment-naive hypertensive patients compared with normotensive controls and to investigate whether a hemodynamic-guided choice of therapy improves blood pressure (BP) control within 4 weeks. METHOD This exploratory post hoc analysis used data of a randomized parallel-group trial including 80 outpatients with newly diagnosed arterial hypertension (AHT), randomized to four antihypertensive first-line monotherapies, and 20 age-matched and sex-matched normotensive controls. Hemodynamic profiles were measured at baseline and after four weeks of treatment. On the basis of the hemodynamic profiles, the most appropriate pharmacological treatment was determined retrospectively and patients were categorised to have received concordant (ConTG) or discordant treatment (DisTG). RESULTS In the hypertensive group, hypervolemia with vasoconstriction was the predominant hemodynamic profile in 48% of patients and hypervolemia without vasoconstriction in 45%, compared with 15 and 50%, respectively, in the control group. After 4 weeks of treatment, the mean (±SD) 24-h BP was 129.9 (±11.0)/81.5 (±8.0) mmHg in the DisTG vs. 133.9 (±12.3)/84.0 (±9.1) mmHg in the ConTG (P = 0.158/0.222). The mean 24-h BP reductions were -9.7 (±10.1)/-5.0 (±6.2) mmHg in the DisTG and -12.4 (±14.8)/-6.9(±6.9) mmHg in the ConTG (P = 0.353/0.223). After 4 weeks of treatment, the BP control rate was 53.7% (43/80) among all, 55.7% (29/52) in the DisTG and 48% (12/25) in the ConTG (P = 0.628). CONCLUSION Our findings do not support the hypothesis that personalized treatment initiation based on hemodynamic profiles improves BP control in newly diagnosed hypertensive outpatients.

Recently, ACC/AHA and ESC/ESH guidelines defined different office blood pressure measurement (OBPM) procedures and ranges. We aimed to describe the effect of the different methods to calculate OBPM on BP classification. Four standardised OBPM were performed in 802 patients within a single visit. BP values were calculated (EUR-/US-BPM) and categorised (EUR-/US-Ranges) according to ACC/AHA and ESC/ESH guidelines. Comparing the BPM procedures, the mean absolute difference of systolic and diastolic BP was 4 (SD ± 5) and 3 (SD ± 3) and a difference ≥ 5 mmHg was found in 35% and 16%, respectively. There was an increase of grade 1/2 arterial hypertension of 87% and 120% comparing BP values categorised according to US-Ranges with EUR-Ranges after applying EUR- or US-BPM to all (p

Importance Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, −3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39];P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration ClinicalTrials.gov Identifier:NCT00512759

BACKGROUND The 2017 American hypertension guidelines [American College of Cardiology/American Heart Association (ACC/AHA)] define a blood pressure measurement (BPM) procedure that differs from the Canadian Hypertension Education Program (CHEP) guidelines. We studied the impact of the BPM procedure on arterial hypertension (AHT) prevalence rate. METHODS In 805 subjects, the mean of the first and second BPM (adapted ACC/AHA procedure) was compared with the mean of the second and third BPM (CHEP procedure). All BPMs were taken at a single occasion. According to ACC/AHA definition, office blood pressure (OBP) of

Objective:A cuffless blood pressure (BP) measurement device (TestBP) using pulse-transit time (PTT) for beat-to-beat calculation of BP is in clinical use. Recently, we published data, demonstrating a significant difference between TestBP and a cuff-based standard 24 h BP device (RefBP) with signific

Objective:A cuffless blood pressure measurement device (TestBP) using pulse transit time for beat-to-beat calculation of blood pressure (BP) is in clinical use. Recently, we compared TestBP against standard cuff-based device (RefBP) over 24 hours (h); showing significantly higher BP values with Test

Objective:Arterial Hypertension (AHT) is characterised by different hemodynamic modulators, which can be non-invasively assessed using the HOTMAN® System, a very low-current thoracic bioimpedance method to estimate modulators such as volemia, inotropy, chronotropy and vasoactivity, and express them

The risk stratification in patients presenting with acute dyspnoea remains a challenge. We therefore conducted a prospective, observational cohort study enrolling 292 patients presenting to the emergency department with acute dyspnoea. A proteomic approach for antibody-free targeted protein quantification based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth factor)-binding protein 2] levels. Final diagnosis and death during follow-up were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final diagnosis in 54% of patients. In both AHF (P

BurriE,HochholzerK,ArenjaN,Martin-Bras- chlerH,KaestnerL,GekelerH,HatziisaakT,Buttiker M, Fraulin A, Potocki M, Breidthardt T, Reichlin T, SocratesT,TwerenboldR,MuellerC (UniversityHos- pitalBasel,Basel;UniversityHospital,Basel,Switzer- land).B-typenatriureticpeptideintheevaluationand management of dyspnoea in primary care. J Intern Med 2012; 272:504-513. Objectives. The rapid and accurate diagnosis of heart failureinprimary careisamajorunmetclinicalneed. We evaluated the additional use of B-type natriuretic peptide(BNP)levels. Design.Arandomizedcontrolledtrial.

Background— The early and noninvasive differentiation of ischemic and nonischemic acute heart failure (AHF) in the emergency department (ED) is an unmet clinical need. Methods and Results— We quantified cardiac hemodynamic stress using B-type natriuretic peptide (BNP) and cardiomyocyte damage using 2 different cardiac troponin assays in 718 consecutive patients presenting to the ED with AHF (derivation cohort). The diagnosis of ischemic AHF was adjudicated using all information, including coronary angiography. Findings were validated in a second independent multicenter cohort (326 AHF patients). Among the 718 patients, 400 (56%) were adjudicated to have ischemic AHF. BNP levels were significantly higher in ischemic compared with nonischemic AHF (1097 [604–1525] pg/mL versus 800 [427–1317] pg/mL; P P P =0.002]). The diagnostic accuracy of BNP, cTnT, and s-cTnI for the diagnosis of ischemic AHF, as quantified by the area under the receiver-operating characteristic curve, was low (0.58 [95% CI, 0.54–0.63], 0.61 [95% CI, 0.57–0.66], and 0.59 [95% CI,0.54–0.65], respectively). These findings were confirmed in the validation cohort. Conclusions— At presentation to the ED, patients with ischemic AHF exhibit more extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF. However, the overlap is substantial, resulting in poor diagnostic accuracy.

Arenja N, Reichlin T, Drexler B, Oshima S, Denhaerynck K, Haaf P, Potocki M, Breidthardt T, Noveanu M, Stelzig C, Heinisch C, Twerenbold R, Reiter M, Socrates T, Mueller C (University Hospital, Basel). Sensitive cardiac troponin in the diagnosis and risk stratification of acute heart failure. J Intern Med 2012; 271: 598–607. Background. The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). Methods. Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (

Cardiac disease is the major cause of death in patients undergoing chronic haemodialysis. Recent studies have found that B-type natriuretic peptide (BNP) levels accurately reflect the cardiovascular burden of dialysis patients. However, the prognostic potential of BNP measurements in dialysis patients remains unknown.The study included 113 chronic dialysis patients who were prospectively followed up. Levels of BNP were measured at baseline and every 6 months thereafter. The potential of baseline BNP and annual BNP changes to predict all-cause and cardiac mortality were assessed as endpoints. Median follow-up was 735 (354-1459) days; 35 (31%) patients died, 17 (15%) of them from cardiac causes. Baseline BNP levels were similar among survivors and non-survivors, and failed to predict all-cause and cardiac death. Cardiac death was preceded by a marked increase in BNP levels. In survivors BNP levels remained stable [median change: +175% (+20-+384%) vs. -14% (-35-+35%) over the 18 months preceding either death or the end of follow-up, P0.001]. Hence, annual BNP changes adequately predicted all-cause and cardiac death in the subsequent year {AUC(all-cause) = 0.70 [SD 0.05, 95% CI (0.60-0.81)]; AUC(cardiac) = 0.82 [SD 0.04, 95%CI (0.73-0.90)]}. A BNP increase of 40% provided the best cut-off level. Cox regression analysis confirmed that annual increases over 40% were associated with a seven-fold increased risk for all-cause and cardiac death.Annual BNP increases above 40% predicted all-cause and cardiac death in the subsequent year. Hence, serially measuring BNP levels may present a novel tool for risk stratification and treatment guidance of end-stage renal disease patients on chronic dialysis.

We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p

The overproduction of acid and the associated illnesses linked to hypersecretion have a lifetime prevalence of 25-35% in the United States. Although a variety of pharmaceutical agents have been used to reduce the production of acid, alarming new evidence questions the long-term efficacy and safety of the agents. These issues coupled with the delayed onset of action and the return of symptoms in over 60% of the patients is less than satisfactory. The purpose of this study was to determine whether administration of a zinc salt could lead to a rapid and sustained increase in gastric pH in both animals and in humans and provide a new rapid acid suppression therapy.Intracellular pH was measured with 2',7'-bis-(2-carboxyethyl)-5-and-6-carboxy-fluorescein in both human and rat gastric glands following an acid load±a secretagogue. In a separate series of studies, whole stomach acid secretion was monitored in rats. A final study used healthy human volunteers while monitoring with a gastric pH measurement received placebo, zinc salt, or a zinc salt and proton pump inhibitor (PPI).We demonstrate that exposure to ZnCl(2) immediately abolished secretagogue-induced acid secretion in isolated human and rat gastric glands, and in intact rat stomachs. Chronic low-dose zinc exposure effectively inhibited acid secretion in whole stomachs and isolated glands. In a randomized cross-over study in 12 volunteers, exposure to a single dose of ZnCl(2) raised intragastric pH for over 3 h, including a fast onset of effect.Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models.

The study objective was to investigate the prognostic utility and patient-specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay.; Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases.; In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary end-point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT-proBNP.; Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL?¹, P > 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P > 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1-year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL?¹) significantly predicted 1-year mortality (HR 2.3, P > 0.001).; In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30-day and 1-year mortality and might improve risk stratification already provided by BNP or NT-proBNP.

Intravenous nitrate therapy has been shown to improve short-term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high-dose nitrate strategy in the Emergency Department and the general ward remains unknown.; A total of 128 consecutive acute heart failure patients were either treated with standard therapy or high-dose sublingual and transdermal nitrates on top of standard of care treatment. Cardiac recovery, quantified by B-type natriuretic peptide (BNP) levels during the first 48 h, was the primary endpoint. Secondary endpoints ascertained the safety of the nitrate therapy.; The high nitrate group received higher doses of nitrates during the first 48 h compared to the standard therapy group [82.4 mg (46.2-120.6) vs. 20 mg (10-30) respectively, P > 0.001]. The amount of diuretics given in both groups was similar. BNP levels decreased in all patients (P > 0.0001). However, the BNP decrease was larger in the high-dose nitrate group (P > 0.0001). The larger decrease in BNP in the high-dose nitrate group was already apparent 12 h after the initiation of treatment. After 48 h BNP values decreased by an average of 29 +/- 4.9% in the high-dose nitrate strategy group compared to 15 +/- 5.4% during standard therapy. There was a strong trend towards fewer ICU admissions in the high-dose nitrate group [high-dose nitrates: 2 cases (4%) vs. standard therapy: 9 cases (13%); P = 0.06]. During the study period, no intergroup changes were observed in blood pressure, RIFLE classes of acute kidney injury or troponin T. In-hospital and 90-day outcome was similar amongst the two groups.; A noninvasive high-dose nitrate strategy on top of standard therapy is safe and notably accelerates cardiac recovery in patients observed on the general ward.

Dyspnea is the most common presenting symptom of patients with acute heart failure (AHF). Although dyspnea is an important target for treatment in clinical practice and clinical trials, there remains a lack of consensus on how to assess it. We describe and recommend to use absolute scales such the Likert 5-point or the Visual Analogue Scale rather than any comparator scale such as the Likert 7-point scale. We further recommend starting dyspnea measurements in sitting position and perform, if possible, similar measurements in lying position. The same set of measurements may be repeated as needed during the time course of disease and the treatment.

Excessive gastric acid secretion plays an important role in the pathogenesis of peptic ulcers. Dexamethasone, a widely used drug, is known to stimulate gastric acid secretion and increase the incidence of peptic ulcers. However little is known about the mechanism of the dexamethasone's effect on parietal cells. The present study was performed to investigate the contribution of the phosphatidylinositol-3-kinase (PI3 kinase) to dexamethasone induced stimulation of gastric acid secretion. In vivo pretreatment with dexamethasone injections (150 microg/100g for 3 days) or in vitro exposure to (10 microM for > 20 minutes) significantly increased acid secretion in isolated gastric glands approximately 2-3 fold. The dexamethasone induced stimulation of gastric acid secretion was concentration dependent and significantly blunted by the H+/K2+ ATPase inhibitor omeprazole (200 microM), the PI3 kinase inhibitor Wortmannin (500 nM), the protein kinase inhibitor staurosporine (2.5 microM) and the Cl(-) channel blocker NPPB (100 microM); but not by the H(2) antagonist cimetidine (100 microM). In conclusion, it was observed that dexamethasone's effect on proton extrusion requires the activity of a PI3 kinase pathway, an apical Cl(-) channel and the H2+/K2+ ATPase.

The gastric H+,K+-ATPase of the parietal cell is responsible for acid secretion in the stomach and is the main target in the pharmacological treatment of acid-related diseases. Omeprazole and other benzimidazole drugs, although having delayed efficacy if taken orally, have high success rates in the treatment of peptic ulcer disease. Potassium competitive acid blockers (P-CAB) compete with K+ for binding to the H+,K+-ATPase and thereby they inhibit acid secretion. In this study, the in vitro properties of AZD0865, a reversible H+,K+-ATPase inhibitor of gastric acid secretion, are described. We used a digital-imaging system and the pH sensitive dye BCECF to observe proton efflux from hand-dissected rat gastric glands. Glands were stimulated with histamine (100 μM) and exposed to a bicarbonate- and Na+-free perfusate to induce an acid load. H+,K+-ATPase inhibition was determined by calculating pHi recovery (dpH/dT) in the presence of omeprazole (10–200 μM) or AZD0865 (0.01–100 μM). The efficacies of both drugs were compared. Our data show that acid secretion is inhibited by both the proton pump inhibitor omeprazole and the P-CAB AZD0865. Complete inhibition of acid secretion by AZD0865 had a rapid onset of activation, was reversible, and occurred at a 100-fold lower dose than omeprazole (1 μM AZD0865 vs. 100 μM omeprazole). This study demonstrates that AZD0865 is a potent, fast-acting inhibitor of gastric acid secretion, effective at lower concentrations than drugs of the benzimidazole class. Therefore, these data strongly suggest that AZD0865 has great potential as a fast-acting, low-dose inhibitor of acid secretion.

The vacuolar-type H-ATPase (V-ATPase) plays an important role in the active acidification of intracellular organelles. In certain specialized cells, such as the renal intercalated cell, apical V-ATPase can also function as a proton secretion pathway. In the parietal cells of the stomach, it has been thought that acid secretion is controlled solely via the H,K-ATPase. However, recent observations suggest that functional V-ATPase is necessary for acid secretion to take place. This study aimed to investigate and characterize the role of V-ATPase in parietal cell proton transport. Individual rat gastric glands were incubated with the pH-sensitive dye (BCECF) to monitor changes in intracellular pH in real time. Parietal cell V-ATPase activity was measured by quantifying the rate of intracellular alkalinization (ΔpH/minute) following an acid load, while excluding the contribution of non-V-ATPase proton transport mechanisms through pharmacological inhibition or ion substitution. Expression of V-ATPase was confirmed by immunohistochemistry. We observed concanamycin A-sensitive V-ATPase activity in rat parietal cells following intracellular acidification and H,K-ATPase inhibition. Furthermore, V-ATPase-mediated proton transport could be abolished by inhibiting trafficking mechanisms with paclitaxel and by stimulating H,K-ATPase with acid secretagogues. Our results propose that parietal cells contain a functional V-ATPase that can be mobilized using a microtubule network. V-ATPase may function as an auxiliary acid secretion or proton-buffering pathway in parietal cells, which is inactive during H,K-ATPase activity. Our findings may have important implications for patients experiencing acid breakthrough under proton pump inhibitor therapy.

To determine the relationship between central venous pressure (CVP) and renal function in patients with acute heart failure (AHF) presenting to the emergency department.Central venous pressure was determined non-invasively using compression sonography in 140 patients with AHF at presentation. Worsening renal function (WRF) was defined as an increase in serum creatinine ≥ 0.3 mg/dL during hospitalization. In the study cohort [age 77 ± 12 years, B-type natriuretic peptide 1862 ± 1564 pg/mL, left ventricular ejection fraction 40 ± 15%, estimated glomerular filtration rate (eGFR) 58 ± 28 mL/min, and CVP 13.2 ± 6.9 cmH(2)O], 51 patients (36%) developed WRF. No significant association between CVP at presentation or discharge and concomitant eGFR (r = 0.005, P = 0.419 and r = 0.013, P = 0.313, respectively) was observed. However, in patients with systolic blood pressure (SBP)110 mmHg and concomitant high CVP (15 cmH(2)O), eGFR was significantly lower at presentation and discharge (29 ± 17 vs. 47 ± 19 mL/min/1.73 m(2), P = 0.039 and 26 ± 10 vs. 53 ± 26 mL/min/1.73 m(2), P = 0.013, respectively). Central venous pressure at presentation and at discharge did not differ between patients with or without in-hospital WRF (12.6 ± 7.2 vs. 13.5 ± 6.7 cmH(2)O, P = 0.503 and 7.4 ± 6.5 vs. 7.7 ± 5.7 cmH(2)O, P = 0.799, respectively) (receiver-operating characteristic analysis 0.543, P = 0.401 and 0.531, P = 0.625, respectively). However, patients with CVP in the lowest tertile (10 cmH(2)O) at presentation were more likely to develop WRF within the first 24 h than patients with CVP in the highest tertile (15 cmH(2)O) (18 vs. 4%, P = 0.046).In AHF, combined low SBP and high CVP predispose to lower eGFR. However, lower CVP may also be associated with short-term WRF. The pathophysiology of WRF and the role of CVP seem to be more complex than previously thought.

Objectives The purpose of this study was to evaluate the utility of B-type natriuretic peptide (BNP) to predict blood pressure (BP) response in patients with renal artery stenosis (RAS) after renal angioplasty and stenting (PTRA). Methods In 120 patients with RAS and hypertension referred for PTRA, 24-h ambulatory BP recordings were obtained before and 6 months after intervention. BNP was measured before, 1 day and 6 months after PTRA. Results BP improved in 54% of patients. Median BNP levels pre-intervention were 97 pg ml −1 (interquartile range (IQR) 35–250) and decreased significantly within 1 day of PTRA to 62 pg ml −1 (IQR 24–182) ( p −1 (IQR 31–190) at 6 months. The area under the receiver operating curve for pre-intervention BNP to predict BP improvement was 0.57 (95% confidence interval (CI) 0.46–0.67). Pre-intervention BNP >50 pg ml −1 was seen in 79% of patients with BP improvement compared with 56% in patients without improvement ( p = 0.01). In a multivariate logistic regression analysis, BNP >50 pg ml −1 was significantly associated with BP improvement (odds ratio (OR) 4.0, 95% CI 1.2–13.2). Conclusions BNP levels are elevated in patients with RAS and decrease after revascularisation. Although BNP does not seem useful as a continuous variable, pre-interventional BNP >50 pg ml −1 may be helpful to identify patients in whom PTRA will improve BP.

Background: Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF). Methods: We prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses. Results: MPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited [area under the ROC curve (AUC) 0.53] and inferior to that of BNP (AUC 0.95, P < 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO >99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (≤99 vs >99 pmol/L) and BNP (median of ≤847 vs >847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P < 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045). Conclusions: MPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.

The recent European Society of Cardiology (ESC) guidelines delineate the diagnosis and management of distinct categories of acute heart failure syndromes. However, physicians dealing with these patients may need guidance in choosing therapeutic alternatives as soon as the dyspneic patient arrives at the emergency department, until distinct categories of the ESC guidelines are identified. Hence, this manuscript summarizes practical recommendations for the very early management of patients with acute heart failure syndromes. The recommendations are based on a clinical classification system considering the initial systolic blood pressure and other symptoms. Early initiation of diagnostic and goal-directed treatment strategies are key factors in improving patient outcomes. Early and frequent reassessment is also imperative so that adjustments to the initial therapeutic approach can be made, as clinically indicated.

To investigate the relationship between central venous pressure (CVP) at presentation to the emergency room (ER) and the risk of cardiac rehospitalization and mortality in patients with decompensated heart failure (DHF).Central venous pressure was determined non-invasively using high-resolution compression sonography at presentation in 100 patients with DHF. Cardiac hospitalizations and cardiac and all-cause mortality were assessed as a function of continuous CVP levels and predefined CVP categories (low6 cm H(2)O, intermediate 6-23 cm H(2)O, and high23 cm H(2)O). Endpoints were adjudicated blinded to CVP. At presentation, mean age was 78 +/- 11 years, 60% of patients were male, mean B-type natriuretic peptide level was 1904 +/- 1592 pg/mL, and mean CVP was 13.7 +/- 7.0 cm H(2)O (range 0-33). During follow-up (median 12 months), 25 cardiac rehospitalizations, 26 cardiac deaths, and 7 non-cardiac deaths occurred. Univariate and stepwise multivariate Cox regression analysis revealed an independent relationship between CVP and cardiac rehospitalization (HR 1.09, 95% CI 1.01-1.18, P = 0.034). Kaplan-Meier analyses confirmed a stepwise increase in cardiac rehospitalization for low-to-high CVP (log-rank test P = 0.015). No association between CVP and (cardiac) mortality was detectable.Central venous pressure at ER presentation in patients with DHF is an independent predictor of cardiac rehospitalization but not of cardiac and all-cause mortality.

Copeptin (the glycosylated 39–amino acid C-terminal fragment of the arginine vasopressin (AVP)1 precursor peptide), when measured with a novel assay (1), has emerged as a promising marker for the early diagnosis of acute myocardial infarction (MI)(2) and a powerful prognostic marker in a variety of settings. The underlying mechanism is thought to be the role of copeptin as a measure of a high individual stress level(3). Interestingly, exercise seems to elicit a significant increase in circulating copeptin concentrations within minutes(4). The aim of our study was to assess the copeptin response to exercise and its determinants. We studied 414 consecutive patients undergoing myocardial perfusion scintigraphy (n = 253) or cardiopulmonary exercise testing (CPET) (n = 161) with upright symptom-limited cycle ergometer tests (increments of 10–25 W/min). In the CPET cohort, arterial samples for blood gas analysis were obtained at rest and peak exercise and were analyzed immediately. In all patients, venous blood was drawn immediately from a catheter in an antecubital vein with the patient in the seated position (rest) before the test and immediately after test termination (peak exercise). These samples were collected in EDTA-containing tubes, placed on ice, and centrifuged at 3000 g . Plasma samples were stored at …

Background: Peak oxygen uptake (peak VO2) is a predictor of outcome in patients with lung disease. In these patients, peak VO2 is typically determined by ventilation and gas exchange. However, it is not well known whether cardiac strain contributes to peak VO2 in patients with chronic lung disease. Objective: To assess the relationship between several novel biomarkers reflecting different aspects of cardiac function and peak VO2 in patients with chronic lung disease. Methods: Plasma concentrations of midregional pro-A-type natriuret- ic peptide (MR-proANP), midregional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and C-terminal provasopressin (copeptin) were measured in 85 patients with a variety of chronic pulmonary diseases [age 57 ± 14 years, forced expiratory volume in the 1st second (FEV1) 76 ± 23% of the predicted value] undergoing maximal cardiopulmonary exercise testing (peak VO2 18.6 ± 6.6 ml/kg/min). Results: Raised MR-proANP (r = –0.54), MR- proADM (r = –0.54), and CT-proET-1 (r = –0.49; p < 0.001 for all) but not copeptin (r = –0.05; p = 0.68) concentrations were associated with lower peak VO2, and these associations were independent of age, gender, medication, FEV1 and oxygenation. The relationship between MR-proANP, MR-proADM, and CT-proET-1 and peak VO2 was significant whether patients had an obstructive ventilatory disease or not. Conclusions: In patients with chronic lung disease, several biomarkers known to reflect measures of cardiac function were associated with peak VO2 independent of lung function, indicating that cardiac strain may contribute to exercise limitation in these patients due to concomitant cardiac disease or in the context of a pulmonary-cardiac interaction.

The cystic fibrosis transmembrane conductance regulator (CFTR) is recognized as a multifunctional protein that is involved in Cl(-) secretion, as well as acting as a regulatory protein. In order for acid secretion to take place a complex interaction of transport proteins and channels must occur at the apical pole of the parietal cell. Included in this process is at least one K(+) and Cl(-) channel, allowing for both recycling of K(+) for the H,K-ATPase, and Cl(-) secretion, necessary for the generation of concentrated HCl in the gastric gland lumen. We have previously shown that an ATP-sensitive potassium channel (K(ATP)) is expressed in parietal cells. In the present study we measured secretagogue-induced acid secretion from wild-type and DeltaF508-deficient mice in isolated gastric glands and whole stomach preparations. Secretagogue-induced acid secretion in wild-type mouse gastric glands could be significantly reduced with either glibenclamide or the specific inhibitor CFTR-inh172. In DeltaF508-deficient mice, however, histamine-induced acid secretion was significantly less than in wild-type mice. Furthermore, immunofluorescent localization of sulfonylurea 1 and 2 failed to show expression of a sulfonylurea receptor in the parietal cell, thus further implicating CFTR as the ATP-binding cassette transporter associated with the K(ATP) channels. These results demonstrate a regulatory role for the CFTR protein in normal gastric acid secretion.